Ictalurus punctatus},
url = {http://www.sciencedirect.com/science/article/pii/S1050464811004761}
}
@ARTICLE{Prieto2007,
author = {Prieto, Ana I. and Jakomin, Marcello and Segura, Ignacio and Pucciarelli,
M. Graciela and Ramos-Morales, Francisco and Garcia-del Portillo,
Francisco and Casadesus, Josep},
title = {The GATC-Binding Protein SeqA Is Required for Bile Resistance and
Virulence in Salmonella enterica Serovar Typhimurium},
journal = {J. Bacteriol.},
year = {2007},
volume = {189},
pages = {8496--8502},
number = {23},
month = dec,
abstract = {Disruption of the seqA gene of Salmonella enterica serovar Typhimurium
causes defects similar to those described in E. coli: filament formation,
aberrant nucleoid segregation, induction of the SOS response, envelope
instability, and increased sensitivity to membrane-damaging agents.
Differences between SeqA- mutants of E. coli and S. enterica, however,
are found. SeqA- mutants of S. enterica form normal colonies and
do not exhibit alterations in phage plaquing morphology. Lack of
SeqA causes attenuation of S. enterica virulence by the oral route
but not by the intraperitoneal route, suggesting a virulence defect
in the intestinal stage of infection. However, SeqA- mutants are
fully proficient in the invasion of epithelial cells. We hypothesize
that attenuation of SeqA- mutants by the oral route may be caused
by bile sensitivity, which in turn may be a consequence of envelope
instability.},
url = {http://jb.asm.org/cgi/content/abstract/189/23/8496}
}
@ARTICLE{Prieto2011,
author = {Prieto, Ana I. and Kahramanoglou, Christina and Ali, Ruhi M. and
Fraser, Gillian M. and Seshasayee, Aswin S. N. and Luscombe, Nicholas
M.},
title = {Genomic analysis of DNA binding and gene regulation by homologous
nucleoid-associated proteins IHF and HU in Escherichia coli K12},
journal = {Nucleic Acids Res.},
year = {2011},
pages = {gkr1236},
abstract = {IHF and HU are two heterodimeric nucleoid-associated proteins (NAP)
that belong to the same protein family but interact differently with
the DNA. IHF is a sequence-specific DNA-binding protein that bends
the DNA by over 160{degrees}. HU is the most conserved NAP, which
binds non-specifically to duplex DNA with a particular preference
for targeting nicked and bent DNA. Despite their importance, the
in vivo interactions of the two proteins to the DNA remain to be
described at a high resolution and on a genome-wide scale. Further,
the effects of these proteins on gene expression on a global scale
remain contentious. Finally, the contrast between the functions of
the homo- and heterodimeric forms of proteins deserves the attention
of further study. Here we present a genome-scale study of HU- and
IHF binding to the Escherichia coli K12 chromosome using ChIP-seq.
We also perform microarray analysis of gene expression in single-
and double-deletion mutants of each protein to identify their regulons.
The sequence-specific binding profile of IHF encompasses [~]30% of
all operons, though the expression of <10% of these is affected by
its deletion suggesting combinatorial control or a molecular backup.
The binding profile for HU is reflective of relatively non-specific
binding to the chromosome, however, with a preference for A/T-rich
DNA. The HU regulon comprises highly conserved genes including those
that are essential and possibly supercoiling sensitive. Finally,
by performing ChIP-seq experiments, where possible, of each subunit
of IHF and HU in the absence of the other subunit, we define genome-wide
maps of DNA binding of the proteins in their hetero- and homodimeric
forms.},
doi = {10.1093/nar/gkr1236},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/gkr1236v1.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/gkr1236v1}
}
@ARTICLE{Primeau2003,
author = {Primeau, Mélanie and Gagnon, Jacynthe and Momparler, Richard L.},
title = {Synergistic antineoplastic action of DNA methylation inhibitor 5-AZA-2′-deoxycytidine
and histone deacetylase inhibitor depsipeptide on human breast carcinoma
cells},
journal = {Int. J. Cancer},
year = {2003},
volume = {103},
pages = {177--184},
number = {2},
abstract = {Abstract 10.1002/ijc.10789.abs During tumorigenesis, cancer-related
genes can be silenced by aberrant DNA methylation and by changes
in chromatin structure. It has been reported that 5-aza-2′-deoxycytidine,
a potent inhibitor of DNA methylation, in combination with histone
deacetylase inhibitors, can produce a synergistic reactivation of
these genes. The aim of our study was to investigate the in vitro
antineoplastic activity of 5-aza-2′-deoxycytidine in combination
with depsipeptide, a potent histone deacetylase inhibitor, against
MDA-MB-231 and MDA-MB-435 human breast carcinoma cell lines. We observed
that the combination of 5-aza-2′-deoxycytidine and depsipeptide
produced a synergistic antineoplastic effect against these tumor
cells as compared to either agent administered alone. We also investigated
the effect of this drug combination on the activation of maspin and
gelsolin expression. These 2 genes whose function is to suppress
tumor metastasis have been reported to be silenced by epigenetic
events in breast cancer. Using semi-quantitative RT-PCR, we observed
that 5-aza-2′-deoxycytidine in combination with depsipeptide produced
a greater reactivation of both maspin and gelsolin as compared to
each agent alone. The synergistic interaction between 5-aza-2′-deoxycytidine
and depsipeptide on breast carcinoma cell lines provides a rationale
to investigate this interesting drug combination in future clinical
trials on patients with advanced breast cancer. © 2002 Wiley-Liss,
Inc.},
issn = {1097-0215},
keywords = {breast cancer, 5-aza-2′-deoxycytydine, depsipeptide, maspin, gelsolin,
DNA methylation, histone deacetylation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.10789}
}
@ARTICLE{Primo2006,
author = {Primo, Daniel and Flores, Juan and Quijano, Sandra and Sanchez, MarÃa
Luz and Sarasquete, MarÃa Eugenia and Del Pino-Montes, Javier and
Gaarder, Per Ivar and Gonzalez, Marcos and Orfao, Alberto},
title = {Impact of BCR/ABL gene expression on the proliferative rate of different
subpopulations of haematopoietic cells in chronic myeloid leukaemia},
journal = {British Journal of Haematology},
year = {2006},
volume = {135},
pages = {43--51},
number = {1},
abstract = {Summary Despite the effects of BCR ABL on cell proliferation, no study
has compared the proliferative rate of different haematopoietic cell
compartments from chronic myeloid leukaemia (CML) with those of normal
bone marrow (NBM). We comparatively analysed the cell cycle distribution
and BCR/ABL expression in different compartments of BM cells from
15 CML and 11 NBM. Overall, our results showed similar proliferative
indices in CML patients and NBM. However, CD34+ myeloid precursors
from CML patients displayed an increased proportion of SÂ +Â G2/M-phase
cells (P = 0·04), while no significant differences were found
between CML and NBM for other BM cell subsets analysed. In BM cells
separated by fluorescence-activated cell sorting, decreasing levels
of BCR/ABL mRNA were found from CD34+/CD38+ myeloid precursors to
myeloblasts; BCR/ABL expression increased afterwards with a peak
at the myelocyte/metamyelocyte stage, decreasing in the more mature
band/neutrophil compartment. Unexpectedly, BCR/ABL gene expression
showed an inverse correlation with the proportion of SÂ +Â G2/M-phase
cells (R = −0·33; P = 0·04). These results suggest that in
CML, BCR/ABL expression is associated with an increased proliferation
of CD34+ myeloid haematopoietic progenitor cells but not of other
more mature myeloid precursors, as confirmed by the observation of
an inverse correlation between the amount of BCR/ABL transcripts
and the proportion of SÂ +Â G2/M-phase cells.},
issn = {1365-2141},
keywords = {BCR/ABL, flow cytometry, cell cycle analysis, RQ-PCR, gene expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2006.06265.x}
}
@ARTICLE{Primrose2010,
author = {Primrose, S. and Woolfe, M. and Rollinson, S.},
title = {Food forensics: methods for determining the authenticity of foodstuffs},
journal = {Trends in Food Science \& Technology},
year = {2010},
volume = {21},
pages = {582--590},
number = {12},
month = dec,
abstract = {Verifying the description of food in terms of its composition, processing
or origin is challenging, but important in protecting consumers and
enforcing food law. The UK Food Standards Agency's authenticity programme
has funded a large number of projects to utilise different technologies
for determining the authenticity of foodstuffs. This review highlights
the practical challenges faced in developing authenticity methods,
and focuses on the techniques that have been the most successful
(stable isotope analysis, genomics and proteomics), giving examples
of their application.},
issn = {0924-2244},
url = {http://www.sciencedirect.com/science/article/pii/S0924224410002001}
}
@ARTICLE{Prinos2011,
author = {Prinos, Panagiotis and Garneau, Daniel and Lucier, Jean-François
and Gendron, Daniel and Couture, Sonia and Boivin, Marianne and Brosseau,
Jean-Philippe and Lapointe, Elvy and Thibault, Philippe and Durand,
Mathieu and Tremblay, Karine and Gervais-Bird, Julien and Nwilati,
Hanad and Klinck, Roscoe and Chabot, Benoit and Perreault, Jean-Pierre
and Wellinger, Raymund J and Elela, Sherif Abou},
title = {Alternative splicing of SYK regulates mitosis and cell survival},
journal = {Nat Struct Mol Biol},
year = {2011},
volume = {advance online publication},
pages = {--},
month = may,
comment = {10.1038/nsmb.2040},
issn = {1545-9985},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nsmb.2040}
}
@ARTICLE{Prins2010,
author = {Prins, John M. and Park, Sunyoung and Lurie, Diana I.},
title = {Decreased Expression of the Voltage-Dependent Anion Channel in Differentiated
PC-12 and SH-SY5Y Cells Following Low-Level Pb Exposure},
journal = {Toxicol. Sci.},
year = {2010},
volume = {113},
pages = {169--176},
number = {1},
month = jan,
abstract = {Lead (Pb) has been shown to disrupt cellular energy metabolism, which
may underlie the learning deficits and cognitive dysfunctions associated
with environmental Pb exposure. The voltage-dependent anion channel
(VDAC) plays a central role in regulating energy metabolism in neurons
by maintaining cellular ATP levels and regulating calcium buffering,
and studies have shown that VDAC expression is associated with learning
in mice. In this study, we examined the effect of 5 and 10{micro}M
Pb on VDAC expression in vitro in order to determine whether Pb alters
VDAC expression levels in neuronal cell lines. PC-12 and SH-SY5Y
cells were used since they differentiate to resemble primary neuronal
cells. VDAC expression levels were significantly decreased 48 h after
exposure to Pb in both cell lines. In contrast, exposure to 24 h
of hypoxia failed to produce a decrease in VDAC, suggesting that
decreased VDAC expression is not a general cellular stress response
but is a result of Pb exposure. This decreased VDAC expression was
also correlated with a corresponding decrease in cellular ATP levels.
Real-time reverse transcription-polymerase chain reaction demonstrated
a significant decrease in messenger RNA levels for the VDAC1 isoform,
indicating that Pb reduces transcription of VDAC1. These results
demonstrate that exposure to 5 and 10{micro}M Pb reduces VDAC transcription
and expression and is associated with reduced cellular ATP levels.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/113/1/169}
}
@ARTICLE{Print2004,
author = {Print, Cristin and Valtola, Reija and Evans, Amanda and Lessan, Khashayar
and Malik, Shazia and Smith, Stephen},
title = {Soluble factors from human endometrium promote angiogenesis and regulate
the endothelial cell transcriptome},
journal = {Hum. Reprod.},
year = {2004},
volume = {19},
pages = {2356--2366},
number = {10},
month = oct,
abstract = {BACKGROUND: Angiogenesis and vascular remodeling play critical roles
in the cyclical growth and regression of endometrium. They also appear
to play roles in the pathogenesis of endometriosis. METHODS and RESULTS:
Supernatants were collected from cultured endometrium isolated from
women with and without endometriosis. These supernatants induced
endothelial cell proliferation and angiogenesis in vitro. They contained
vascular endothelial growth factor (VEGF)-A, and their proliferative
effects on endothelial cells were partially abrogated by a blocking
anti-VEGF-A antibody. Gene array analysis showed that culture supernatants
from proliferative phase endometrium, and to a lesser extent secretory
phase endometrium, induced significant changes in the transcriptome
of endothelial cells. We could not detect any association between
endometriosis and the ability of endometrial-derived soluble factors
to promote angiogenesis or to regulate the endothelial transcriptome.
In addition, we could not detect any association between endometriosis
and the concentration of VEGF-A in supernatants from cultured endometrium
or in menstrual effluent. CONCLUSIONS: We have shown that endometrium
cultured in vitro produced soluble factors, including VEGF-A, that
promoted angiogenesis. Proliferative phase endometrium promoted significant
endothelial cell transcriptome changes that appear overall to be
pro-angiogenic. These transcriptome changes provide insight into
the dynamic control of vessel structure on which both eutopic endometrium
and endometriotic lesions depend.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/19/10/2356}
}
@ARTICLE{Prinzen2009,
author = {Prinzen, Claudia and Trümbach, Dietrich and Wurst, Wolfgang and Endres,
Kristina and Postina, Rolf and Fahrenholz, Falk},
title = {Differential gene expression in ADAM10 and mutant ADAM10 transgenic
mice},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {66},
number = {1},
abstract = {BACKGROUND:In a transgenic mouse model of Alzheimer disease (AD),
cleavage of the amyloid precursor protein (APP) by the a-secretase
ADAM10 prevented amyloid plaque formation, and alleviated cognitive
deficits. Furthermore, ADAM10 overexpression increased the cortical
synaptogenesis. These results suggest that upregulation of ADAM10
in the brain has beneficial effects on AD pathology.RESULTS:To assess
the influence of ADAM10 on the gene expression profile in the brain,
we performed a microarray analysis using RNA isolated from brains
of five months old mice overexpressing either the a-secretase ADAM10,
or a dominant-negative mutant (dn) of this enzyme. As compared to
non-transgenic wild-type mice, in ADAM10 transgenic mice 355 genes,
and in dnADAM10 mice 143 genes were found to be differentially expressed.
A higher number of genes was differentially regulated in double-transgenic
mouse strains additionally expressing the human APP[V717I] mutant.Overexpression
of proteolytically active ADAM10 affected several physiological pathways,
such as cell communication, nervous system development, neuron projection
as well as synaptic transmission. Although ADAM10 has been implicated
in Notch and ß-catenin signaling, no significant changes in the respective
target genes were observed in adult ADAM10 transgenic mice.Real-time
RT-PCR confirmed a downregulation of genes coding for the inflammation-associated
proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression.
Overexpression of the dominant-negative form dnADAM10 led to a significant
increase in the expression of the fatty acid-binding protein Fabp7,
which also has been found in higher amounts in brains of Down syndrome
patients.CONCLUSION:In general, there was only a moderate alteration
of gene expression in ADAM10 overexpressing mice. Genes coding for
pro-inflammatory or pro-apoptotic proteins were not over-represented
among differentially regulated genes. Even a decrease of inflammation
markers was observed. These results are further supportive for the
strategy to treat AD by increasing the a-secretase activity.},
doi = {10.1186/1471-2164-10-66},
issn = {1471-2164},
pubmedid = {19196476},
url = {http://www.biomedcentral.com/1471-2164/10/66}
}
@ARTICLE{Prior2010,
author = {Prior, Matthew J. and Foletta, Victoria C. and Jowett, Jeremy B.
and Segal, David H. and Carless, Melanie A. and Curran, Joanne E.
and Dyer, Tom D. and Moses, Eric K. and McAinch, Andrew J. and Konstantopoulos,
Nicky and Bozaoglu, Kiymet and Collier, Greg R. and Cameron-Smith,
David and Blangero, John and Walder, Ken R.},
title = {The characterization of Abelson helper integration site-1 in skeletal
muscle and its links to the metabolic syndrome},
journal = {Metabolism},
year = {2010},
volume = {59},
pages = {1057--1064},
number = {7},
month = jul,
abstract = {The human Abelson helper integration site–1 (AHI1) gene is associated
with both neurologic and hematologic disorders; however, it is also
located in a chromosomal region linked to metabolic syndrome phenotypes
and was identified as a type 2 diabetes mellitus susceptibility gene
from a genomewide association study. To further define a possible
role in type 2 diabetes mellitus development, AHI1 messenger RNA
expression levels were investigated in a range of tissues and found
to be highly expressed in skeletal muscle as well as displaying elevated
levels in brain regions and gonad tissues. Further analysis in a
rodent polygenic animal model of obesity and type 2 diabetes mellitus
identified increased Ahi-1 messenger RNA levels in red gastrocnemius
muscle from fasted impaired glucose–tolerant and diabetic rodents
compared with healthy animals (P < .002). Moreover, elevated gene
expression levels were confirmed in skeletal muscle from fasted obese
and type 2 diabetes mellitus human subjects (P < .02). RNAi-mediated
suppression of Ahi-1 resulted in increased glucose transport in rat
L6 myotubes in both the basal and insulin-stimulated states (P <
.01). Finally, single nucleotide polymorphism association studies
identified 2 novel AHI1 genetic variants linked with fasting blood
glucose levels in Mexican American subjects (P < .037). These findings
indicate a novel role for AHI1 in skeletal muscle and identify additional
genetic links with metabolic syndrome phenotypes suggesting an involvement
of AHI1 in the maintenance of glucose homeostasis and type 2 diabetes
mellitus progression.},
issn = {0026-0495},
publisher = {W.B. Saunders},
refid = {S0026-0495(09)00472-7},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0026049509004727?showall=true}
}
@ARTICLE{Prithiviraj2005,
author = {Prithiviraj, B. and Bais, H. P. and Weir, T. and Suresh, B. and Najarro,
E. H. and Dayakar, B. V. and Schweizer, H. P. and Vivanco, J. M.},
title = {Down Regulation of Virulence Factors of Pseudomonas aeruginosa by
Salicylic Acid Attenuates Its Virulence on Arabidopsis thaliana and
Caenorhabditis elegans},
journal = {Infect. Immun.},
year = {2005},
volume = {73},
pages = {5319--5328},
number = {9},
month = sep,
abstract = {Salicylic acid (SA) is a phenolic metabolite produced by plants and
is known to play an important role in several physiological processes,
such as the induction of plant defense responses against pathogen
attack. Here, using the Arabidopsis thaliana-Pseudomonas aeruginosa
pathosystem, we provide evidence that SA acts directly on the pathogen,
down regulating fitness and virulence factor production of the bacteria.
Pseudomonas aeruginosa PA14 showed reduced attachment and biofilm
formation on the roots of the Arabidopsis mutants lox2 and cpr5-2,
which produce elevated amounts of SA, as well as on wild-type Arabidopsis
plants primed with exogenous SA, a treatment known to enhance endogenous
SA concentration. Salicylic acid at a concentration that did not
inhibit PA14 growth was sufficient to significantly affect the ability
of the bacteria to attach and form biofilm communities on abiotic
surfaces. Furthermore, SA down regulated three known virulence factors
of PA14: pyocyanin, protease, and elastase. Interestingly, P. aeruginosa
produced more pyocyanin when infiltrated into leaves of the Arabidopsis
transgenic line NahG, which accumulates less SA than wild-type plants.
This finding suggests that endogenous SA plays a role in down regulating
the synthesis and secretion of pyocyanin in vivo. To further test
if SA directly affects the virulence of P. aeruginosa, we used the
Caenorhabiditis elegans-P. aeruginosa infection model. The addition
of SA to P. aeruginosa lawns significantly diminished the bacterium's
ability to kill the worms, without affecting the accumulation of
bacteria inside the nematodes' guts, suggesting that SA negatively
affects factors that influence the virulence of P. aeruginosa. We
employed microarray technology to identify SA target genes. These
analyses showed that SA treatment affected expression of 331 genes.
It selectively repressed transcription of exoproteins and other virulence
factors, while it had no effect on expression of housekeeping genes.
Our results indicate that in addition to its role as a signal molecule
in plant defense responses, SA works as an anti-infective compound
by affecting the physiology of P. aeruginosa and ultimately attenuating
its virulence.},
url = {http://iai.asm.org/cgi/content/abstract/73/9/5319}
}
@ARTICLE{PRIVAT2010,
author = {PRIVAT, MAUD and AUBEL, CORINNE and ARNOULD, STEPHANIE and COMMUNAL,
YVES and FERRARA, MARC and BIGNON, YVES-JEAN},
title = {AKT and p21WAF1/CIP1 as Potential Genistein Targets in BRCA1-mutant
Human Breast Cancer Cell Lines},
journal = {Anticancer Res},
year = {2010},
volume = {30},
pages = {2049--2054},
number = {6},
month = jun,
abstract = {BRCA1 acts as a tumour suppressor and germ-line mutations within this
gene are found in a large proportion of families with breast cancer.
The aim of our study was to unravel the mechanism of action of genistein,
the major soy phytoestrogen, in BRCA1-mutant human breast cancer
cell lines. Four breast cancer cell lines were studied for their
response to genistein, three of them harbouring different mutations
within the BRCA1 gene (HCC1937, SUM149 and SUM1315 cells) and the
MDA-MB-231 cell line, which expresses a functional BRCA1 protein.
We showed that genistein inhibits proliferation and induces apoptosis
more efficiently in BRCA1-mutant cells than in cells expressing wild-type
BRCA1 protein. Increased AKT and decreased p21WAF1/CIP1 protein levels
could explain the relative resistance to genistein elicited by cells
with wild-type BRCA1. BRCA1-mutant breast cancer cells are highly
sensitive to genistein treatment and p21WAF1/CIP1 and AKT could be
genistein targets in these cells.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/30/6/2049}
}
@ARTICLE{Privat2009,
author = {Privat, Maud and Aubel, Corinne and Arnould, Stéphanie and Communal,
Yves and Ferrara, Marc and Bignon, Yves-Jean},
title = {Breast cancer cell response to genistein is conditioned by BRCA1
mutations},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {379},
pages = {785--789},
number = {3},
month = feb,
abstract = {Soy phytoestrogens, among which genistein, seem to protect from breast
cancer development. In order to study the role of the breast tumour
suppressor BRCA1 in response to genistein, we used a new breast cancer
cell model: the SUM1315MO2 cell line carrying the 185delAG BRCA1
mutation, which we stably transfected with a plasmid encoding wild-type
BRCA1. We showed that growth of BRCA1 mutant cells was strongly inhibited
by genistein whereas it only had a weak effect in cells expressing
wild-type BRCA1 protein. BRCA1 mutant cells hypersensitivity could
be linked to higher expression of ER[beta] gene, which suggests that
genistein may be an efficient inhibitor of cancer development in
BRCA1 mutant breast cancer cells.},
issn = {0006-291X},
keywords = {Genistein, Phytoestrogen, BRCA1, Estrogen receptor beta, ER[beta],
Breast cancer},
url = {http://www.sciencedirect.com/science/article/B6WBK-4V99TXR-C/2/538b4389d161819f27f32a03663a1bfa}
}
@ARTICLE{Priyanka2009,
author = {Priyanka, S. and Jayaram, P. and Sridaran, R. and Medhamurthy, R.},
title = {Genome-Wide Gene Expression Analysis Reveals a Dynamic Interplay
between Luteotropic and Luteolytic Factors in the Regulation of Corpus
Luteum Function in the Bonnet Monkey (Macaca radiata)},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {1473--1484},
number = {3},
month = mar,
abstract = {Although LH is essential for survival and function of the corpus luteum
(CL) in higher primates, luteolysis occurs during nonfertile cycles
without a discernible decrease in circulating LH levels. Using genome-wide
expression analysis, several experiments were performed to examine
the processes of luteolysis and rescue of luteal function in monkeys.
Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted
in differential regulation of 3949 genes, whereas replacement with
exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes
(1563 down-regulation and 2871 up-regulation). A model system for
prostaglandin (PG) F2{alpha}-induced luteolysis in the monkey was
standardized and demonstrated that PGF2{alpha} regulated expression
of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome
revealed that 120 genes were regulated in an antagonistic fashion
by PGF2{alpha}. Based on the microarray data, 25 genes were selected
for validation by real-time RT-PCR analysis, and expression of these
genes was also examined in the CL throughout the luteal phase and
from monkeys treated with human chorionic gonadotropin (hCG) to mimic
early pregnancy. The results indicated changes in expression of genes
favorable to PGF2{alpha} action during the late to very late luteal
phase, and expressions of many of these genes were regulated in an
opposite manner by exogenous hCG treatment. Collectively, the findings
suggest that curtailment of expression of downstream LH-target genes
possibly through PGF2{alpha} action on the CL is among the mechanisms
underlying cross talk between the luteotropic and luteolytic signaling
pathways that result in the cessation of luteal function, but hCG
is likely to abrogate the PGF2{alpha}-responsive gene expression
changes resulting in luteal rescue crucial for the maintenance of
early pregnancy.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/3/1473}
}
@ARTICLE{Prock2007,
author = {Prock, Terasa L. and Miranda, Rajesh C.},
title = {Embryonic Cerebral Cortical Progenitors Are Resistant to Apoptosis,
but Increase Expression of Suicide Receptor DISC-Complex Genes and
Suppress Autophagy Following Ethanol Exposure},
journal = {Alcoholism: Clinical and Experimental Research},
year = {2007},
volume = {31},
pages = {694--703},
number = {4},
abstract = {Background: In utero exposure to ethanol can result in severe fetal
brain defects. Previous studies showed that ethanol induces apoptosis
in differentiated cortical neurons. However, we know little about
ethanol's effects on proliferating embryonic cortical progenitors.
This study investigated the impact of ethanol exposure on the Fas/Apo-1/CD95
suicide receptor pathway, and on the survival of proliferating cortical
neuroepithelial progenitors. Methods: Murine embryonic-derived primary
cortical neuroepithelial cells were maintained as neurosphere cultures
and exposed to a dose range of ethanol for periods ranging from 1
to 5 days. Programmed cell death was measured by 4 independent means
(Annexin-V staining, caspase activation, DNA fragmentation, and autophagic
vacuole formation). Surface Fas/Apo-1 suicide receptor expression
was measured by flow cytometry. Expression of Fas/Apo-1-associated
DISC-complex genes was measured by quantitative polymerase chain
reaction. Results: Ethanol exposure did not substantially increase
apoptosis, necrosis, or surface Fas/Apo-1 expression. Moreover, ethanol
significantly decreased caspase activation and autophagic activity.
Finally, ethanol exposure induced mRNA expression of genes that constitute
the death receptor complex. Conclusions: This study provides surprising
evidence that ethanol does not induce either programmed cell death
or necrosis of immature progenitors during neurogenesis, although
ethanol may render neural progenitors susceptible to future apoptotic
insults. Furthermore, our novel observation that ethanol suppresses
autophagy is consistent with a hypothesis that ethanol promotes premature
neural progenitor maturation. Taken together with our previous data
regarding the role of the Fas/Apo-1 receptor in neural development,
we conclude that ethanol disrupts basic proliferation and differentiation
machinery rather than initiating cell death per se.},
issn = {1530-0277},
keywords = {Fetal Alcohol Syndrome, Neurogenesis, Apoptosis, Fas/Apo-1/CD95, Differentiation},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1530-0277.2007.00354.x}
}
@ARTICLE{Prokopczyk2009,
author = {Prokopczyk, Bogdan and Sinha, Indu and Trushin, Neil and Freeman,
Willard M. and El-Bayoumy, Karam},
title = {Gene expression profiles in HPV-immortalized human cervical cells
treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone},
journal = {Chemico-Biological Interactions},
year = {2009},
volume = {177},
pages = {173--180},
number = {3},
month = feb,
abstract = {Human papillomavirus (HPV) infection is an established etiological
factor for cervical cancer. Epidemiological studies suggest that
smoking in combination with HPV infection plays a significant role
in the etiology of this disease. We have previously shown that the
tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK), is present in human cervical mucus. Here, we hypothesized
that treatment of HPV-16-immortalized human ectocervical cells (Ecto1/E6E7)
with NNK would alter the expression of genes involved in cellular
transformation. Ecto1/E6E7 cells were treated with water (vehicle
control) alone or with 1 [mu]M, 10 [mu]M, and 100 [mu]M of NNK in
water for 12 weeks. The colony-forming efficiency increased following
NNK treatment; the maximum effect was observed after 12 weeks with
100 [mu]M NNK. Microarray analysis revealed that, independent of
the dose of NNK, expression of 30 genes was significantly altered;
22 of these genes showed a dose-response pattern. Genes identified
are categorized as immune response (LTB4R), RNA surveillance pathway
(SMG1), metabolism (ALDH7A1), genes frequently expressed in later
stages of neoplastic development (MT1F), DNA binding (HIST3H3 and
CHD1L), and protein biosynthesis (UBA52). Selected genes were confirmed
by qRT-PCR. Western blot analysis indicates that phosphorylation
of histone 3 at serine 10, a marker of cellular transformation, was
up-regulated in cells treated with NNK. This is the first study showing
that NNK can alter gene expression that may, in part, account for
transformation of HPV-immortalized human cervical cells. The results
support previous epidemiological observations that, in addition to
HPV, tobacco smoking also plays an important role in the development
of cervical cancer.},
issn = {0009-2797},
keywords = {Microarray analysis, NNK, HPV, Cervical cancer},
url = {http://www.sciencedirect.com/science/article/B6T56-4TVTJSC-2/2/73d08fa7b812dfa3f47d1da4cd89bfa1}
}
@ARTICLE{Prokudin2011,
author = {Prokudin, Ivan and Stasyk, Taras and Rainer, Johannes and Bonn, Guenther
K. and Kofler, Reinhard and Huber, Lukas A.},
title = {Comprehensive proteomic and transcriptomic characterization of hepatic
expression signatures affected in p14 liver conditional knockout
mice},
journal = {PROTEOMICS},
year = {2011},
volume = {11},
pages = {469--480},
number = {3},
abstract = {Abstract Scaffold proteins regulate intracellular MAP kinase signaling
by providing critical spatial and temporal specificities. We have
shown previously that the scaffold protein MEK1 partner (MP1) is
localized to late endosomes by the adaptor protein p14. Using conditional
gene disruption of p14 in livers of mice (p14Δhep) we analyzed protein
and transcript signatures in tissue samples. Further biological network
analysis predicted that the differentially expressed transcripts
and proteins are involved in cell cycle progression and regulation
of cellular proliferation. Although some of the here identified signatures
were previously linked to phospho-ERK activity, most of them were
novel targets of the late endosomal p14/MP1/MEK/ERK signaling module.
Finally, the proliferation defect was confirmed in a chemically induced
liver regeneration model in p14Δhep knockout mice.},
doi = {10.1002/pmic.201000400},
issn = {1615-9861},
keywords = {Animal proteomics, Cre recombinase, Liver regeneration, MAPK, Scaffold
proteins},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.201000400}
}
@ARTICLE{Pronk2011,
author = {Tessa E. Pronk and Jochem W. van der Veen and Janine Ezendam and
Henk Van Loveren and Jeroen L.A. Pennings},
title = {Effects of pooling RNA from samples treated with different compounds
for determining class specific biomarkers and processes in toxicogenomics},
journal = {Toxicology in Vitro},
year = {2011},
volume = {25},
pages = {1841 - 1847},
number = {8},
abstract = {Pooling of RNA samples is generally applied to obtain samples that
represent the average signal of biological replicates of a single
treatment. For toxicogenomics, pooling RNA of samples treated by
different compounds could in the same way summarize these compounds
to a single sample with average signals per class. In this study,
we investigated the efficiency of such an approach to establish class
specific differences in gene expression. As an example we took skin
sensitizing compounds as one class and irritating compounds as another.
A direct comparison was made to separately hybridized RNA samples.
We observed that pooling RNA from compounds of a class substantially
increased power to detect significantly regulated genes between classes
because variability between pooled samples was much lower. Within
pools the vast majority of genes maintained patterns of expression
compared to the separately hybridized samples, especially in regulated
genes. Both designs yielded appropriate biomarkers. Biomarkers selected
from the pooled and separate design performed equally in classification
of compounds to their class and relevant processes were found enriched
in both designs. Consequently, pooling of RNA of different compound
treated samples can be applied to determine class specific biomarkers
and processes at much reduced cost and with limited loss of accuracy.},
doi = {10.1016/j.tiv.2011.05.012},
issn = {0887-2333},
keywords = {Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/pii/S088723331100138X}
}
@ARTICLE{Pros2009,
author = {Pros, Eva and Fernández-RodrÃguez, Juana and Canet, Belén and
Benito, Llúcia and Sánchez, Aurora and Benavides, Ana and Ramos,
Feliciano J. and López-Ariztegui, MarÃa Asunción and Capellá,
Gabriel and Blanco, Ignacio and Serra, Eduard and Lázaro, Conxi},
title = {Antisense therapeutics for neurofibromatosis type 1 caused by deep
intronic mutations},
journal = {Hum. Mutat.},
year = {2009},
volume = {30},
pages = {454--462},
number = {3},
abstract = {Abstract 10.1002/humu.20933.abs Neurofibromatosis type 1 (NF1) is
an autosomal dominant disorder affecting 1:3,500 individuals. Disease
expression is highly variable and complications are diverse. However,
currently there is no specific treatment for the disease. NF1 is
caused by mutations in the NF1 gene, approximately 2.1% of constitutional
mutations identified in our population are deep intronic mutations
producing the insertion of a cryptic exon into the mature mRNA. We
used antisense morpholino oligomers (AMOs) to restore normal splicing
in primary fibroblast and lymphocyte cell lines derived from six
NF1 patients bearing three deep intronic mutations in the NF1 gene
(c.288+2025T>G, c.5749+332A>G, and c.7908-321C>G). AMOs were designed
to target the newly created 5′ splice sites to prevent the incorporation
of cryptic exons. Our results demonstrate that AMO treatment effectively
restored normal NF1 splicing at the mRNA level for the three mutations
studied in the different cell lines analyzed. We also found that
AMOs had a rapid effect that lasted for several days, acting in a
sequence-specific manner and interfering with the splicing mechanism.
Finally, to test whether the correction of aberrant NF1 splicing
also restored neurofibromin function to wild-type levels, we measured
the amount of Ras-GTP after AMO treatment in primary fibroblasts.
The results clearly show an AMO-dependent decrease in Ras-GTP levels,
which is consistent with the restoration of neurofibromin function.
To our knowledge this is the first time that an antisense technique
has been usedsuccessfully to correct NF1 mutations opening the possibility
of a therapeutic strategy for this type of mutation not only for
NF1 but for other genetic disorders. Hum Mutat 30, 454–462, 2009.
© 2009 Wiley-Liss, Inc.},
issn = {1098-1004},
keywords = {neurofibromatosis 1, NF1, morpholino, antisense oligonucleotide therapy,
AMO, deep intronic mutation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.20933}
}
@ARTICLE{Prosperi2009,
author = {Prosperi, Jenifer R. and Becher, Kimberly R. and Willson, Tara A.
and Collins, Margaret H. and Witte, David P. and Goss, Kathleen H.},
title = {The APC tumor suppressor is required for epithelial integrity in
the mouse mammary gland},
journal = {J. Cell. Physiol.},
year = {2009},
volume = {220},
pages = {319--331},
number = {2},
abstract = {Abstract 10.1002/jcp.21766.abs Inactivation of the adenomatous polyposis
coli (APC) tumor suppressor has been associated with mammary tumorigenesis
in mouse models and through epidemiological studies of human breast
cancers, but the normal role for APC in mammary development has not
been thoroughly characterized. We report here that ApcMin/+ mice
containing one functional allele of Apc have severely disrupted lobuloalveolar
development during pregnancy and lactation, time points at which
Apc gene expression is at its highest levels in normal mice. This
phenotype was accompanied by altered proliferation during pregnancy
and involution, increased apoptosis throughout lactation, the formation
of preneoplastic lesions and changes in specific genes associated
with each of these processes. Neither modifications in β-catenin
localization, nor the expression of β-catenin transcriptional target
genes, were observed in ApcMin/+ mammary tissues; however, tissues
from lactating ApcMin/+ mice had a significantly altered epithelial
architecture, including disrupted localization of junctional proteins
and polarization. Consistent with these findings, APC knockdown in
non-transformed mouse mammary epithelial cells in vitro resulted
in altered monolayer formation and proliferation without changes
in β-catenin-mediated transcription. These results suggest that
APC expression is tightly regulated during mammary gland development
and is required for normal mammary homeostasis and tumor suppression
primarily through maintaining epithelial integrity. J. Cell. Physiol.
220: 319–331, 2009. © 2009 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.21766}
}
@ARTICLE{Prot2011a,
author = {Prot, Jean Matthieu and Aninat, Caroline and Griscom, Laurent and
Razan, Florence and Brochot, Céline and Guillouzo, Christiane Guguen
and Legallais, Cécile and Corlu, Anne and Leclerc, Eric},
title = {Improvement of HepG2/C3a cell functions in a microfluidic biochip},
journal = {Biotechnology and Bioengineering},
year = {2011},
volume = {108},
pages = {1704--1715},
number = {7},
abstract = {Abstract Current developments in tissue engineering and microtechnology
fields allow the use of microfluidic biochip as microtools for in
vitro investigations. In the present study, we describe the behavior
of HepG2/C3a cells cultivated in a poly(dimethylsiloxane) (PDMS)
microfluidic biochip coupled to a perfusion system. Cell culture
in the microfluidic biochip for 96 h including 72 h of perfusion
provoked a 24 h delay in cell growth compared to plate cultures.
Inside the microfluidic biochip, few apoptosis, and necrosis were
detected along the culture and 3D cell organization was observed.
Regarding the hepatic metabolism, glucose and glutamine consumptions
as well as albumin synthesis were maintained. A transcriptomic analysis
performed at 96 h of culture using Affymetrix GeneChip demonstrated
that 1,025 genes with a fold change above 1.8 were statistically
differentially expressed in the microfluidic biochip cultures compared
to plate cultures. Among those genes, phase I enzymes involved in
the xenobiotic's metabolism such as the cytochromes P450 (CYP) 1A1/2,
2B6, 3A4, 3A5, and 3A7 were up-regulated. The CYP1A1/2 up-regulation
was associated with the appearance of CYP1A1/2's activity evidenced
by using EROD biotransformation assay. Several phase II enzymes such
as sulfotransferases (SULT1A1 and SULT1A2), UDP-glucuronyltransferase
(UGT1A1, UGT2B7) and phase III transporters (such as MDR1, MRP2)
were also up-regulated. In conclusion, microfluidic biochip could
and provide an important insight to exploring the xenobiotic's metabolism.
Altogether, these results suggest that this kind of biochip could
be considered as a new pertinent tool for predicting cell toxicity
and clearance of xenobiotics in vitro. Biotechnol. Bioeng. 2011;
108:1704–1715. © 2011 Wiley Periodicals, Inc.},
doi = {10.1002/bit.23104},
issn = {1097-0290},
keywords = {transcriptomic, PDMS, microfluidic biochip, hepatocytes, liver},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.23104}
}
@ARTICLE{Prot2011,
author = {Jean-Matthieu Prot and Andrei Bunescu and Bénédicte Elena-Hermann
and Caroline Aninat and Leila Choucha Snouber and Laurent Griscom
and Florence Razan and Frederic Bois and Cécile Legallais and Céline
Brochot and Anne Corlu and Marc Emmanuel Dumas and Eric Leclerc},
title = {Predictive toxicology using systemic biology and liver microfluidic
“on chip� approaches: Application to acetaminophen injury},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
pages = { - },
number = {0},
abstract = {We have analyzed transcriptomic, proteomic and metabolomic profiles
of hepatoma cells cultivated inside a microfluidic biochip with or
without acetaminophen (APAP). Without APAP, the results show an adaptive
cellular response to the microfluidic environment, leading to the
induction of anti-oxidative stress and cytoprotective pathways. In
presence of APAP, calcium homeostasis perturbation, lipid peroxidation
and cell death are observed. These effects can be attributed to APAP
metabolism into its highly reactive metabolite, N-acetyl-p-benzoquinone
imine (NAPQI). . That toxicity pathway was confirmed by the detection
of GSH-APAP, the large production of 2-hydroxybutyrate and 3-hydroxybutyrate,
and methionine, cystine, and histidine consumption in the treated
biochips. Those metabolites have been reported as specific biomarkers
of hepatotoxicity and glutathione depletion in the literature. In
addition, the integration of the metabolomic, transcriptomic and
proteomic collected profiles allowed a more complete reconstruction
of the APAP injury pathways. To our knowledge, this work is the first
example of a global integration of microfluidic biochip data in toxicity
assessment. Our results demonstrate the potential of that new approach
to predictive toxicology.},
doi = {10.1016/j.taap.2011.12.017},
issn = {0041-008X},
keywords = {Microfluidic biochip},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11004741}
}
@ARTICLE{Protiva2009,
author = {Protiva, Petr and Cross, Heide S. and Hopkins, Michael E. and Kallay,
Eniko and Bises, Giovanna and Dreyhaupt, Eleanor and Augenlicht,
Leonard and Lipkin, Martin and Lesser, Martin and Livote, Elayne
and Holt, Peter R.},
title = {Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role
of Vitamin D Activity},
journal = {Cancer Prevention Research},
year = {2009},
volume = {2},
pages = {43--51},
number = {1},
month = jan,
abstract = {Postmenopausal hormone replacement therapy lowers colon cancer incidence.
In humans, the mechanism is unknown, but animal models suggest that
it may involve activation of the vitamin D receptor (VDR) pathway.
The aims of our study were to determine whether estrogen intervention
affects global gene expression in rectal mucosal biopsies and whether
vitamin D-related genes are affected. Estradiol was given to raise
serum estradiol to premenopausal levels in 10 postmenopausal women
under close nutritional control. Primary end points were expression
of VDR, CYP24A1, CYP27B1, and E-cadherin in rectal mucosa by reverse
transcription-PCR and examining response to estradiol by genome-wide
arrays. Responses in gene expression in rectal biopsies to estrogen
were determined in each subject individually and compared with a
human estrogen response gene array database and a custom array in
vitro-generated database. Cluster analysis showed that subjects maintained
their overall gene expression profile and that interindividual differences
were greater than intraindividual differences after intervention.
Eight of 10 subjects showed significant enrichment in estrogen-responsive
genes. Gene array group analysis showed activation of the VDR pathway
and down-regulation of inflammatory and immune signaling pathways.
Reverse transcription-PCR analysis showed significant up-regulation
of VDR and E-cadherin, a downstream target of vitamin D action. These
data suggest that the chemopreventive action of hormone replacement
therapy on colon neoplasia results, at least in part, from changes
in vitamin D activity. Evaluation of gene arrays is useful in chemopreventive
intervention studies in small groups of subjects.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/2/1/43}
}
@ARTICLE{Protiva2008,
author = {Protiva, Petr and Hopkins, Michael E. and Baggett, Scott and Yang,
Hui and Lipkin, Martin and Holt, Peter R. and Kennelly, Edward J.
and Bernard, Weinstein I.},
title = {Growth inhibition of colon cancer cells by polyisoprenylated benzophenones
is associated with induction of the endoplasmic reticulum response},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {687--694},
number = {3},
abstract = {Abstract 10.1002/ijc.23515.abs Polyisoprenylated benzophenones derived
from Garcinia xanthochymus have cytotoxic activity in vitro and antitumor
activity in rodent models, but the mechanism is unknown. The purpose
of our study was to examine in parallel molecular pathways that are
targeted by 3 Garcinia-derived benzophenones-xanthochymol (X), guttiferone
E (GE) and guttiferone H (GH), in 3 human colon cancer cell lines,
HCT116, HT29 and SW480. The IC50 concentrations were determined and
the cells were then treated with X, GE or GH at their respective
IC50 or IC50x2 concentrations. Effects on the cell cycle, mitochondrial
membrane potential and apoptosis were assessed by flow cytometry
and caspase activation. Changes in gene expression were assessed
with Illumina 24 K gene arrays. We found that X, GE and GH induced
loss of mitochondrial membrane potential and G1 arrest at their IC50
concentrations and induced caspase activation at IC50 × 2 concentrations.
An analysis of the changes in gene expression revealed that with
all 3 compounds and all 3 cell lines there was a marked increase
in expression of several genes, including XBP1, ATF4 and DDIT3/CHOP,
which are components of the endoplasmic reticulum stress response.
The DDIT4/REDD1 gene, an inhibitor of the mTOR survival pathway,
was also up-regulated. Therefore, X, GE and GH appear to inhibit
the growth of human colon cancer cells, at least in part, by activating
the endoplasmic reticulum stress response and inhibiting the mTOR
cell survival pathway. These combined effects may contribute to the
anticancer activity of these novel compounds. © 2008 Wiley-Liss,
Inc.},
issn = {1097-0215},
keywords = {Garcinia xanthochymus, endoplasmic reticulum stress, unfolded protein,
cell cycle arrest},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23515}
}
@ARTICLE{Protiva2011,
author = {Protiva, Petr and Mason, Joel B. and Liu, Zhenhua and Hopkins, Michael
E. and Nelson, Celeste and Marshall, James R. and Lambrecht, Richard
W. and Pendyala, Swaroop and Kopelovich, Levy and Kim, Myungjin and
Kleinstein, Steven H. and Laird, Peter W. and Lipkin, Martin and
Holt, Peter R.},
title = {Altered Folate Availability Modifies the Molecular Environment of
the Human Colorectum: Implications for Colorectal Carcinogenesis},
journal = {Cancer Prevention Research},
year = {2011},
volume = {4},
pages = {530--543},
number = {4},
month = apr,
abstract = {Low folate status increases colorectal cancer risk. Paradoxically,
overly abundant folate supplementation, which is not uncommon in
the United States, may increase risk. The mechanisms of these effects
are unknown. We conducted two translational studies to define molecular
pathways in the human colon altered either by folate supplementation
or by dietary folate depletion (followed by repletion). In the first
study, 10 healthy, at-risk volunteers (with documented stable/normal
folate intake) received supplemental folic acid (1 mg/d) for 8 weeks.
In the second study, 10 similar subjects were admitted to a hospital
as inpatients for 12 weeks to study folate depletion induced by a
low folate diet. A repletion regimen of folic acid (1 mg/d) was provided
for the last 4 of these weeks. Both studies included an 8-week run-in
period to ensure stabilized folate levels prior to intervention.
We obtained 12 rectosigmoid biopsies (from 4 quadrants of normal-appearing
mucosa 10-15 cm from the anal verge) at baseline and at measured
intervals in both studies for assessing the primary endpoints: genome-wide
gene expression, genomic DNA methylation, promoter methylation (depletion/repletion
study only), and p53 DNA strand breaks. Serum and rectosigmoid folate
concentrations accurately tracked all changes in folate delivery
(P < 0.05). In the first study, gene array analysis revealed that
supplementation upregulated multiple inflammation- and immune-related
pathways in addition to altering several 1-carbon-related enzymes
(P < 0.001). In the second study, folate depletion downregulated
genes involved in immune response, inflammation, the cell cycle,
and mitochondrial/energy pathways; repletion reversed most of these
changes. However, changes in gene expression after repletion in the
second study (involving immune response and inflammation) did not
reach the levels seen after supplementation in the first study. Neither
genomic nor promoter-specific DNA methylation changed during the
course of the depletion/repletion protocol, and genomic methylation
did not change with supplementation in the first study. p53 DNA strand
breaks increased with depletion after 12 weeks. In sum, depletion
downregulates, whereas repletion or supplementation upregulates pathways
related to inflammation and immune response. These findings provide
novel support to the concept that excessive folate supplementation
might promote colorectal carcinogenesis by enhancing proinflammatory
and immune response pathways. These results indicate that modest
changes in folate delivery create substantial changes in the molecular
milieu of the human colon. Cancer Prev Res; 4(4); 530-43. (C)2011
AACR.},
comment = {10.1158/1940-6207.CAPR-10-0143},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/4/4/530}
}
@ARTICLE{Provenzano2010,
author = {Provenzano, Claudia and Pascucci, Barbara and Lupari, Eliana and
Civitareale, Donato},
title = {Large scale analysis of transcription factor TTF-1/NKX2.1 target
genes in GnRH secreting cell line GT1-7},
journal = {Molecular and Cellular Endocrinology},
year = {2010},
volume = {323},
pages = {215--223},
number = {2},
month = jul,
abstract = {TTF-1/Nkx2.1 is a homeodomain-containing transcription factor required
for the proper development of ventral forebrain, including some structures
of the hypothalamus. TTF-1/Nkx2.1 remains expressed in the hypothalamus
after birth and it plays a crucial role during sexual development.
To identify putative TTF-1/Nkx2.1 target genes in GnRH neurons, we
have studied the gene expression profile of the GT1-7 cells exogenously
expressing TTF-1/Nkx2.1 coding gene. Our transcriptome analysis confirms
that TTF-1/Nkx2.1 is involved in neuron morphogenesis and differentiation.
Many of the newly identified TTF-1/Nkx2.1 target genes have a direct
involvement with the central regulation of sexual maturity. In particular,
we have identified Sparc as a gene directly regulated by TTF-1/Nkx2.1
at the promoter level. To further support the role of TTF-1 in GnRH
neurons, we show that Sparc is involved in the regulation of the
GnRH secretion in GT1-7 cells.},
issn = {0303-7207},
keywords = {GnRH, TTF-1/NKX2.1, Hypothalamus, Sexual maturity, Transcription},
url = {http://www.sciencedirect.com/science/article/B6T3G-4YJ4NHW-6/2/750daeb3bae16b3d21660aab5b3e2604}
}
@ARTICLE{Provenzano2008,
author = {Provenzano, Paolo P. and Inman, David R. and Eliceiri, Kevin W. and
Beggs, Hilary E. and Keely, Patricia J.},
title = {Mammary Epithelial-Specific Disruption of Focal Adhesion Kinase Retards
Tumor Formation and Metastasis in a Transgenic Mouse Model of Human
Breast Cancer},
journal = {Am. J. Pathol.},
year = {2008},
volume = {173},
pages = {1551--1565},
number = {5},
month = nov,
abstract = {Focal adhesion kinase (FAK) is a central regulator of the focal adhesion,
influencing cell proliferation, survival, and migration. Despite
evidence demonstrating FAK overexpression in human cancer, its role
in tumor initiation and progression is not well understood. Using
Cre/LoxP technology to specifically knockout FAK in the mammary epithelium,
we showed that FAK is not required for tumor initiation but is required
for tumor progression. The mechanistic underpinnings of these results
suggested that FAK regulates clinically relevant gene signatures
and multiple signaling complexes associated with tumor progression
and metastasis, such as Src, ERK, and p130Cas. Furthermore, a systems-level
analysis identified FAK as a major regulator of the tumor transcriptome,
influencing genes associated with adhesion and growth factor signaling
pathways, and their cross talk. Additionally, FAK was shown to down-regulate
the expression of clinically relevant proliferation- and metastasis-associated
gene signatures, as well as an enriched group of genes associated
with the G2 and G2/M phases of the cell cycle. Computational analysis
of transcription factor-binding sites within ontology-enriched or
clustered gene sets suggested that the differentially expressed proliferation-
and metastasis-associated genes in FAK-null cells were regulated
through a common set of transcription factors, including p53. Therefore,
FAK acts as a primary node in the activated signaling network in
transformed motile cells and is a prime candidate for novel therapeutic
interventions to treat aggressive human breast cancers.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/173/5/1551}
}
@ARTICLE{Provost2011,
author = {Bertille Provost and Véronique Jouan and Frédérique Hilliou and
Pierre Delobel and Pauline Bernardo and Marc Ravallec and François
Cousserans and Eric Wajnberg and Isabelle Darboux and Philippe Fournier
and Michael R. Strand and Anne-Nathalie Volkoff},
title = {Lepidopteran transcriptome analysis following infection by phylogenetically
unrelated polydnaviruses highlights differential and common responses},
journal = {Insect Biochemistry and Molecular Biology},
year = {2011},
volume = {41},
pages = {582 - 591},
number = {8},
abstract = {The Polydnaviridae is a family of double-stranded DNA viruses that
are symbionts of parasitoid wasps. The family is currently divided
into two genera, the Ichnovirus (IV) and Bracovirus (BV), which are
associated with wasps in the families Ichneumonidae and Braconidae,
respectively. IVs and BVs have similar immunosuppressive and developmental
effects on parasitized hosts but their encapsidated genomes largely
encode different genes. To assess whether IV and BV infection has
similar or disparate effects on the transcriptome of shared hosts,
we characterized the effects of Hyposoter didymator Ichnovirus (HdIV)
and Microplitis demolitor Bracovirus (MdBV) on the fat body and hemocyte
transcriptome of Spodoptera frugiperda (Lepidoptera: Noctuidae).
Our results indicated that HdIV and MdBV infection alters the abundance
of a relatively low proportion of S. frugiperda transcripts at 24 h
post-infection. AÂ majority of the transcripts affected by infection
also differed between MdBV and HdIV. However, we did identify some
host transcripts that were similarly affected by both viruses. A
majority of these genes were transcribed in the fat body and most
belonged to functional classes with roles in immunity, detoxification,
or cell structure. Particularly prominent in this suite of transcripts
were genes encoding for predicted motor-related and collagen IV-like
proteins. Overall, our data suggest that the broadly similar effects
that HdIV and MdBV have on host growth and immunity are not due to
these viruses inducing profound changes in host gene expression.
Given though that IVs and BVs encode few shared genes, the host transcripts
that are similarly affected by HdIV and MdBV could indicate convergence
by each virus to target a few processes at the level of transcription
that are important for successful parasitism of hosts by H. didymator
and M. demolitor.},
doi = {10.1016/j.ibmb.2011.03.010},
issn = {0965-1748},
keywords = {Polydnavirus},
url = {http://www.sciencedirect.com/science/article/pii/S0965174811000786}
}
@ARTICLE{Provot2007,
author = {Provot, Sylvain and Zinyk, Dawn and Gunes, Yasemin and Kathri, Richa
and Le, Quynh and Kronenberg, Henry M. and Johnson, Randall S. and
Longaker, Michael T. and Giaccia, Amato J. and Schipani, Ernestina},
title = {Hif-1{alpha} regulates differentiation of limb bud mesenchyme and
joint development},
journal = {J. Cell Biol.},
year = {2007},
volume = {177},
pages = {451--464},
number = {3},
month = may,
abstract = {Recent evidence suggests that low oxygen tension (hypoxia) may control
fetal development and differentiation. A crucial mediator of the
adaptive response of cells to hypoxia is the transcription factor
Hif-1{alpha}. In this study, we provide evidence that mesenchymal
condensations that give origin to endochondral bones are hypoxic
during fetal development, and we demonstrate that Hif-1{alpha} is
expressed and transcriptionally active in limb bud mesenchyme and
in mesenchymal condensations. To investigate the role of Hif-1{alpha}
in mesenchymal condensations and in early chondrogenesis, we conditionally
inactivated Hif-1{alpha} in limb bud mesenchyme using a Prx1 promoter-driven
Cre transgenic mouse. Conditional knockout of Hif-1{alpha} in limb
bud mesenchyme does not impair mesenchyme condensation, but alters
the formation of the cartilaginous primordia. Late hypertrophic differentiation
is also affected as a result of the delay in early chondrogenesis.
In addition, mutant mice show a striking impairment of joint development.
Our study demonstrates a crucial, and previously unrecognized, role
of Hif-1{alpha} in early chondrogenesis and joint formation.},
url = {http://jcb.rupress.org/cgi/content/abstract/177/3/451}
}
@ARTICLE{Prueitt2008,
author = {Prueitt, Robyn L. and Yi, Ming and Hudson, Robert S. and Wallace,
Tiffany A. and Howe, Tiffany M. and Yfantis, Harris G. and Lee, Dong.
H. and Stephens, Robert M. and Liu, Chang-Gong and Calin, George
A. and Croce, Carlo M. and Ambs, Stefan},
title = {Expression of microRNAs and protein-coding genes associated with
perineural invasion in prostate cancer},
journal = {Prostate},
year = {2008},
volume = {68},
pages = {1152--1164},
number = {11},
abstract = {Abstract 10.1002/pros.20786.abs Background Perineural invasion (PNI)
is the dominant pathway for local invasion in prostate cancer. To
date, only few studies have investigated the molecular differences
between prostate tumors with PNI and those without it. Methods To
evaluate the involvement of both microRNAs and protein-coding genes
in PNI, we determined their genome-wide expression with a custom
microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas
with PNI and 7 without it. In situ hybridization (ISH) and immunohistochemistry
was used to validate candidate genes. Results Unsupervised classification
of the 57 adenocarcinomas revealed two clusters of tumors with distinct
global microRNA expression. One cluster contained all non-PNI tumors
and a subgroup of PNI tumors. Significance analysis of microarray
data yielded a list of microRNAs associated with PNI. At a false
discovery rate (FDR) <10%, 19 microRNAs were higher expressed in
PNI tumors than in non-PNI tumors. The most differently expressed
microRNA was miR-224. ISH showed that this microRNA is expressed
by perineural cancer cells. The analysis of protein-coding genes
identified 34 transcripts that were differently expressed by PNI
status (FDR < 10%). These transcripts were down-regulated in
PNI tumors. Many of those encoded metallothioneins and proteins with
mitochondrial localization and involvement in cell metabolism. Consistent
with the microarray data, perineural cancer cells tended to have
lower metallothionein expression by immunohistochemistry than nonperineural
cancer cells. Conclusions Although preliminary, our findings suggest
that alterations in microRNA expression, mitochondrial function,
and cell metabolism occur at the transition from a noninvasive prostate
tumor to a tumor with PNI. Prostate 68: 1152–1164, 2008. Published
2008 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {invasion, prostate tumor, gene expression profile, microRNA},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20786}
}
@ARTICLE{Przybyla2006,
author = {Przybyla, Beata and Gurley, Cathy and Harvey, Jonathan F. and Bearden,
Edward and Kortebein, Patrick and Evans, William J. and Sullivan,
Dennis H. and Peterson, Charlotte A. and Dennis, Richard A.},
title = {Aging alters macrophage properties in human skeletal muscle both
at rest and in response to acute resistance exercise},
journal = {Experimental Gerontology},
year = {2006},
volume = {41},
pages = {320--327},
number = {3},
month = mar,
abstract = {Macrophages are involved in skeletal muscle repair through pro-inflammatory
and alternative functions. We tested the hypothesis that aging alters
the abundance and properties of skeletal muscle macrophages that
will influence their functional response to acute resistance exercise.
Total macrophages (CD68+), as well as pro- (CD11b+) and anti-inflammatory
(CD163+) subpopulations and associated cytokine mRNAs were quantified
in vastus lateralis biopsies from young (N=17) and elderly (N=17)
males pre- and 72 h post-exercise. Pre-exercise, young muscle tended
to possess a greater number of macrophages, whereas elderly muscle
possessed higher levels of IL-1[beta] (P=0.001), IL-1RA (P=0.003),
and IL-10 (P=0.028). Post-exercise, total macrophages did not change
in either group, however, the number of CD11b+ (P=0.039) and CD163+
(P=0.026) cells increased 55 and 29%, respectively, but only in the
young. IL-1[beta] (P=0.006), IL-10 (P=0.016), and AMAC-1 (P=0.044)
also increased, approximately two-fold, and again only in the young.
Quantitation of CD11b+ and CD163+ cells suggests that the majority
of resident macrophages possess alternative functions, and a small
subpopulation participates in the inflammatory response. Both subpopulations
increased their activity post-exercise, exclusively in the young.
These findings suggest that aging results in a defective regulation
of muscle macrophage function, both at baseline and in response to
resistance exercise, that may limit muscle hypertrophy in older adults.},
issn = {0531-5565},
keywords = {Skeletal muscle, Interleukin, Macrophage, Resistance exercise, Inflammation,
Aging},
url = {http://www.sciencedirect.com/science/article/B6T6J-4J5T5VN-2/2/dfd1c99833c3f64ce86fd7b41737bebe}
}
@ARTICLE{Przybyla-Zawislak2005,
author = {Przybyla-Zawislak, Beata D. and Kim, Chung S. and Ali, Syed F. and
Slikker, Jr., William and Binienda, Zbigniew K.},
title = {The differential JunB responses to inhibition of succinate dehydrogenase
in rat hippocampus and liver},
journal = {Neuroscience Letters},
year = {2005},
volume = {381},
pages = {354--357},
number = {3},
month = jun,
abstract = {The inhibitor of mitochondrial enzyme succinate dehydrogenase, 3-nitropropionic
acid (3-NPA), induces cellular energy deficit followed by oxidative
stress, secondary excitotoxicity and neuronal degeneration. The fast
activation of Jun and Fos proteins and other proteins encoding inducible
transcription factors (ITFs) occurs in most tissues upon exposure
to a variety of stressors including exposure to mitochondrial inhibitors.
However, the consequences of this activation can differ dramatically
in different organs. For example, while activation of the same ITFs
may lead to apoptosis and necrosis in neurons it may stimulate liver
regeneration. Here, we report the alterations in mRNAs levels of
c-Fos, JunB, and Krox20 proteins induced in the rat brain and liver
by the acute exposure to 3-NPA at 30 mg/kg, s.c. While the increase
of c-fos transcripts was observed in both the hippocampus and liver,
the junb transcript increased in the hippocampus but decreased in
the liver. No changes were observed in krox-20 mRNA in the hippocampus.
Interestingly, there was a large variation in krox-20 mRNA levels
in the liver among animals within the same experimental group. In
conclusion, out of the three ITFs transcripts examined here junb
may activate different pathways depending on the tissue as indicated
by differential responses to mitochondrial inhibition in the hippocampus
and liver.},
issn = {0304-3940},
keywords = {Hippocampus, c-fos, junb, krox-20, Liver, 3-Nitropropionic acid, Rat},
url = {http://www.sciencedirect.com/science/article/B6T0G-4FTJ0D7-1/2/36145812080d6d0e4e5191d306a0d789}
}
@ARTICLE{PRZYBYLA-ZAWISLAK2005,
author = {PRZYBYLA-ZAWISLAK, BEATA D. and THORN, BRETT T. and ALI, SYED F.
and DENNIS, RICHARD A. and AMATO, ANTONINO and VIRMANI, ASHRAF and
BINIENDA, ZBIGNIEW K.},
title = {Identification of Rat Hippocampal mRNAs Altered by the Mitochondrial
Toxicant, 3-NPA},
journal = {Annals of the New York Academy of Sciences},
year = {2005},
volume = {1053},
pages = {162--173},
number = {1},
abstract = {Abstract: 3-Nitropropionic acid (3-NPA) is a model mitochondrial inhibitor
that causes selective neurodegeneration in brain. 3-NPA-induced neurodegeneration
occurs via a secondary neurotoxicity, caused initially by ATP depletion
and redox changes in the cell. It is known that the hippocampal degeneration
caused by mitochondrial dysfunction affects learning and memory,
cognitive functions commonly disturbed in neurodegenerative diseases.
The 3-NPA- treated animal model can be used to study molecular mechanisms
underlying selective degeneration in the brain. In this study, a
microarray approach was utilized to define changes in the expression
of 530 genes in the rat hippocampus after acute exposure to 3-NPA
at 30 mg/kg, sc. The microarray data were collected at 30 min, 2
h, and 4 h post-3-NPA. Statistical modeling using an ANOVA mixed
model applied to Van der Waerden scores of rank-transformed intensity
data was used to assign statistical significance to 44 transcripts.
These transcripts represent genes associated with energy metabolism,
calcium homeostasis, the cytoskeleton, neurotransmitter metabolism,
and other cellular functions. Changes in the transcripts of genes
encoding 2 transporters [blood-brain specific anion transporter (Slco1c1)
and sodium-dependent inorganic phosphate cotransporter (Slc17a7)]
were confirmed by real-time RT-PCR. In conclusion, this study identified
2 new potential targets for enhancement of neuroprotection or inhibition
of neurodegeneration associated with ATP depletion in the hippocampus.},
issn = {1749-6632},
keywords = {microarrays, RT-PCR, hippocampus, gene expression, Slco1c1, Slc17a7,
glutamate vesicular transporter, 3-nitropropionic acid (3-NPA), rat},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1749-6632.2005.tb00022.x}
}
@ARTICLE{Przybysz2009,
author = {Przybysz, Aaron J. and Choe, Keith P. and Roberts, L. Jackson and
Strange, Kevin},
title = {Increased age reduces DAF-16 and SKN-1 signaling and the hormetic
response of Caenorhabditis elegans to the xenobiotic juglone},
journal = {Mechanisms of Ageing and Development},
year = {2009},
volume = {130},
pages = {357--369},
number = {6},
month = jun,
abstract = {Cells adapt to stressors by activating mechanisms that repair damage
and protect them from further injury. Stress-induced damage accumulates
with age and contributes to age associated diseases. Increased age
attenuates the ability to mount a stress response, but little is
known about the mechanisms by which this occurs. To begin addressing
this problem, we studied hormesis in the nematode Caenorhabditis
elegans. When exposed to a low concentration of the xenobiotic juglone,
young worms mount a robust hormetic stress response and survive a
subsequent exposure to a higher concentration of juglone that is
normally lethal to naïve animals. Old worms are unable to mount this
adaptive response. Microarray and RNAi analyses demonstrate that
an altered transcriptional response to juglone is responsible in
part for the reduced adaptation of old worms. Many genes differentially
regulated in young versus old animals are known or postulated to
be regulated by the FOXO homologue DAF-16 and the Nrf2 homologue
SKN-1. Activation of these pathways is greatly reduced in juglone
stressed old worms. DAF-16- and SKN-1-like transcription factors
play highly conserved roles in regulating stress resistance and longevity
genes. Our studies provide a foundation for developing a molecular
understanding of how age affects cytoprotective transcriptional pathways.},
issn = {0047-6374},
keywords = {Stress resistance, Acclimation, Electrophile, Oxidative stress, Transcription
factor},
url = {http://www.sciencedirect.com/science/article/B6T31-4VTVPV3-1/2/b1a29dcd4cd3f5dc8781a4a5d948ee2b}
}
@ARTICLE{Ptacek2007,
author = {Ptacek, T. and Song, C. and Walker, C.L. and Sell, S.M.},
title = {Physical mapping of distinct 7q22 deletions in uterine leiomyoma
and analysis of a recently annotated 7q22 candidate gene},
journal = {Cancer Genetics and Cytogenetics},
year = {2007},
volume = {174},
pages = {116--120},
number = {2},
month = apr,
abstract = {Uterine leiomyoma (UL) is a benign, smooth muscle tumor of the uterus
affecting a significant proportion of women of reproductive age.
Deletions involving chromosome 7q22 are common in UL and vary in
length. Previously reported 7q22 deletion intervals were physically
mapped using information from the recently completed human genome
sequence. Four distinct deletion intervals, which included a microdeletion
reported by our laboratory, were identified. This microdeletion contains
two known genes, ORC5L and LHFPL3. The single deleted marker in the
microdeletion was mapped within the LHFPL3 locus. The ORC5L gene
has been studied in UL. Conversely, LHFPL3 has been annotated only
recently, and has therefore not been studied in UL. The predicted
LHFPL3 protein sequence contained a polyalanine domain, and a signature
sequence for the PMP22 Claudin protein family. Members of this family
are transmembrane proteins with roles in differentiation, proliferation,
and extracellular matrix formation, and have been implicated in other
tumors. Differences in LHFPL3 expression were observed in both human
and Eker rat UL. Our results provide evidence for four distinct 7q22
deletion intervals, each with multiple candidate genes, including
the recently identified LHFPL3 gene.},
issn = {0165-4608},
url = {http://www.sciencedirect.com/science/article/B6T53-4NJDCN6-6/2/322f733e4174ab58d15bb28c9074e8ef}
}
@ARTICLE{Pucheu-Haston2010,
author = {Pucheu-Haston, Cherie M. and Copeland, Lisa B. and Vallanat, Beena
and Boykin, Elizabeth and Ward, Marsha D.W.},
title = {Biomarkers of acute respiratory allergen exposure: Screening for
sensitization potential},
journal = {Toxicology and Applied Pharmacology},
year = {2010},
volume = {244},
pages = {144--155},
number = {2},
month = apr,
abstract = {Effective hazard screening will require the development of high-throughput
or in vitro assays for the identification of potential sensitizers.
The goal of this preliminary study was to identify potential biomarkers
that differentiate the response to allergens vs non-allergens following
an acute exposure in naïve individuals. Female BALB/c mice received
a single intratracheal aspiration exposure to Metarhizium anisopliae
crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced
Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1,
3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated
to determine total and differential cellularity, total protein concentration
and LDH activity. RNA was isolated from lung tissue for microarray
analysis and qRT-PCR. MACA administration induced a rapid increase
in BALF neutrophils, lymphocytes, eosinophils and total protein compared
to BSA or HBSS. Microarray analysis demonstrated differential expression
of genes involved in cytokine production, signaling, inflammatory
cell recruitment, adhesion and activation in 3 and 12 h MACA-treated
samples compared to BSA or HBSS. Further analyses allowed identification
of ~ 100 candidate biomarker genes. Eleven genes were selected for
further assessment by qRT-PCR. Of these, 6 demonstrated persistently
increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while
C3ar1 increased from 6-24 h. In conclusion, a single respiratory
exposure of mice to an allergenic mold extract induces an inflammatory
response which is distinct in phenotype and gene transcription from
the response to a control protein. Further validation of these biomarkers
with additional allergens and irritants is needed. These biomarkers
may facilitate improvements in screening methods.},
issn = {0041-008X},
keywords = {Asthma, Biomarkers, Hazard screening, Intratracheal aspiration, Gene
expression microarray, Quantitative real-time polymerase chain reaction
(qRT-PCR)},
url = {http://www.sciencedirect.com/science/article/B6WXH-4Y35TG0-4/2/16efee296c8b2f2823858504129d429c}
}
@ARTICLE{Puckette2011,
author = {Puckette, Michael and Iyer, Niranjani J. and Tang, Yuhong and Dai,
Xin-Bin and Zhao, Patrick and Mahalingam, Ramamurthy},
title = {Differential mRNA Translation in Medicago truncatula Accessions with
Contrasting Responses to Ozone-Induced Oxidative Stress},
journal = {Mol Plant},
year = {2011},
pages = {ssr069},
abstract = {Acute ozone is a model abiotic elicitor of oxidative stress and a
useful tool for understanding biochemical and molecular events during
oxidative signaling. Two Medicago truncatula accessions with contrasting
responses to ozone were used to examine translational regulation
during ozone stress. In ozone-resistant JE154, significant reduction
in ribosome loading was observed within one hour of ozone treatment,
suggesting energy homeostasis as a vital factor for oxidative stress
management. Polysomal RNA-based expression profiling with Affymetrix
arrays revealed extensive changes in the translatomes of both accessions.
Messenger RNAs with low GC content in their 5' and 3'-UTRs were preferentially
associated with polysomes during oxidative stress. Genebins analysis
revealed extensive changes in various gene ontologies in both accessions.
Extensive changes in nicotinate and nicotinamide metabolism genes
were corroborated with increased levels of NAD+ and NADH in JE154.
The significantly lower NAD+:NADH redox status in JE154, in conjunction
with higher ATP amounts, provided a cellular milieu conducive for
overcoming oxidative stress. Low levels of ATP, NADH, and suppression
of antioxidant defense responses, abet build-up of ozone-derived
ROS and ultimately lead to oxidative cell death in Jemalong.},
doi = {10.1093/mp/ssr069},
eprint = {http://mplant.oxfordjournals.org/cgi/reprint/ssr069v1.pdf},
url = {http://mplant.oxfordjournals.org/cgi/content/abstract/ssr069v1}
}
@ARTICLE{Pugazhendhi2007,
author = {Pugazhendhi, D. and Sadler, A. J. and Darbre, P. D.},
title = {Comparison of the global gene expression profiles produced by methylparaben,
n-butylparaben and 17β-oestradiol in MCF7 human breast cancer cells},
journal = {J. Appl. Toxicol.},
year = {2007},
volume = {27},
pages = {67--77},
number = {1},
abstract = {Abstract 10.1002/jat.1200.abs Since the alkyl esters of p-hydroxybenzoic
acid (parabens) can be measured intact in the human breast and possess
oestrogenic properties, it has been suggested that they could contribute
to an aberrant burden of oestrogen signalling in the human breast
and so play a role in the rising incidence of breast cancer. However,
although parabens have been shown to regulate a few single genes
(reporter genes, pS2, progesterone receptor) in a manner similar
to that of 17β-oestradiol, the question remains as to the full extent
of the similarity in the overall gene profile induced in response
to parabens compared with 17β-oestradiol. The GE-Amersham CodeLink
20 K human expression microarray system was used to profile the expression
of 19881 genes in MCF7 human breast cancer cells following a 7-day
exposure to 5 × 10−4m methylparaben, 10−5mn-butylparaben and
10−8m 17β-oestradiol. At these concentrations, the parabens gave
growth responses in MCF7 cells of similar magnitude to 17β-oestradiol.
The study identified genes which are upregulated or downregulated
to a similar extent by methylparaben, n-butylparaben and 17β-oestradiol.
However, the majority of genes were not regulated in the same way
by all three treatments. Some genes responded differently to parabens
from 17β-oestradiol, and furthermore, differences in expression
of some genes could be detected even between the two individual parabens.
Therefore, although parabens possess oestrogenic properties, their
mimicry in terms of global gene expression patterns is not perfect
and differences in gene expression profiles could result in consequences
to the cells that are not identical to those following exposure to
17β-oestradiol. Copyright © 2006 John Wiley & Sons, Ltd.},
issn = {1099-1263},
keywords = {global gene expression profiles, microarray, parabens, environmental
oestrogen, breast cancer cells, MCF7 cells},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jat.1200}
}
@ARTICLE{Pugazhenthi2007,
author = {Pugazhenthi, Subbiah and Akhov, Leonid and Selvaraj, Gopalan and
Wang, Maorong and Alam, Jawed},
title = {Regulation of heme oxygenase-1 expression by demethoxy curcuminoids
through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells},
journal = {Am J Physiol Endocrinol Metab},
year = {2007},
volume = {293},
pages = {E645--655},
number = {3},
month = sep,
abstract = {Curcumin (diferuloylmethane), a component of turmeric, has been shown
to have therapeutic properties. Induction of phase 2 detoxifying
enzymes is a potential mechanism through which some of the actions
of curcumin could proceed. Heme oxygenase-1 (HO-1), an antioxidant
phase 2 enzyme, has been reported to have cytoprotective effects
in pancreatic [beta]-cells. Curcumin on further purification yields
demethoxy curcumin (DMC) and bisdemethoxy curcumin (BDMC). The objective
of the present study was to determine the mechanism by which these
purified curcuminoids induce HO-1 in MIN6 cells, a mouse [beta]-cell
line. Demethoxy curcuminoids induced HO-1 promoter linked to the
luciferase reporter gene more effectively than curcumin. The induction
was dependent on the presence of antioxidant response element (ARE)
sites containing enhancer regions (E1 and E2) in HO-1 promoter and
nuclear translocation of nuclear factor-E2-related factor (Nrf2),
the transcription factor that binds to ARE. Curcuminoids stimulated
multiple signaling pathways that are known to induce HO-1. Inhibition
of specific signaling pathways with pharmacological inhibitors and
cotransfection experiments suggested the involvement of phosphotidylinositol
3-kinase and Akt. Real-time quantitative RT-PCR analysis showed significant
elevation in the mRNA levels of HO-1 and two other phase 2 enzymes,
the regulatory subunit of glutamyl cysteine ligase, which is needed
for the synthesis of glutathione, and NAD(P)H:quinone oxidoreductase,
which detoxifies quinones. DMC and BDMC induced the expression of
HO-1 and translocated Nrf2 to nucleus in [beta]-cells of mouse islets.
Our observations suggest that demethoxy curcuminoids could be used
to induce a cellular defense mechanism in [beta]-cells under conditions
of stress as seen in diabetes.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/293/3/E645}
}
@ARTICLE{Pugazhenthi2009,
author = {Pugazhenthi, Subbiah and Gilden, Donald H. and Nair, Sreekala and
McAdoo, Anne and Wellish, Mary and Brazeau, Elizabeth and Mahalingam,
Ravi},
title = {Simian Varicella Virus Induces Apoptosis in Monkey Kidney Cells by
the Intrinsic Pathway and Involves Downregulation of Bcl-2 Expression},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {9273--9282},
number = {18},
month = sep,
abstract = {Simian varicella virus (SVV) causes varicella in primates, becomes
latent in ganglionic neurons, and reactivates to produce zoster.
SVV produces a cytopathic effect in monkey kidney cells in tissue
culture. To study the mechanism by which SVV-infected cells die,
we examined markers of apoptosis 24 to 64 h postinfection (hpi).
Western blot analysis of virus-infected cell lysates revealed a significant
increase in the levels of the cleaved active form of caspase-3, accompanied
by a parallel increase in caspase-3 activity at 40 to 64 hpi. Caspase-9,
a marker for the intrinsic pathway, was activated significantly in
SVV-infected cells at all time points, whereas trace levels of the
active form of caspase-8, an extrinsic pathway marker, was detected
only at 64 hpi. Bcl-2 expression at the mRNA and protein levels was
decreased by 50 to 70% throughout the course of virus infection.
Release of cytochrome c, an activator of caspase-9, from mitochondria
into the cytoplasm was increased by 200% at 64 hpi. Analysis of Vero
cells infected with SVV expressing green fluorescent protein (SVV-GFP)
at 64 hpi revealed colocalization of the active forms of caspase-3
and caspase-9 and terminal deoxynucleotidyltransferase-mediated dUTP-biotin
nick end labeling (TUNEL) staining with GFP. A significant decrease
in the bcl-2 mRNA levels along with an abundance of mRNA specific
for SVV genes 63, 40, and 21 was seen in the fraction of Vero cells
that were infected with SVV-GFP. Together, these findings indicate
that SVV induces apoptosis in cultured Vero cells through the intrinsic
pathway in which Bcl-2 is downregulated.},
url = {http://jvi.asm.org/cgi/content/abstract/83/18/9273}
}
@ARTICLE{Pugnale2009,
author = {Pugnale, Paolo and Pazienza, Valerio and Guilloux, Kévin and Negro,
Francesco},
title = {Hepatitis delta virus inhibits alpha interferon signaling},
journal = {Hepatology},
year = {2009},
volume = {49},
pages = {398--406},
number = {2},
abstract = {Abstract 10.1002/hep.22654.abs Hepatitis delta virus (HDV) can cause
severe acute and chronic liver disease in patients infected with
hepatitis B virus. Interferon-α (IFN-α) is the only treatment reported
to be effective in chronic hepatitis delta, albeit in a minority
of patients. The molecular mechanisms underlying resistance to therapy
are unclear. IFN-α–induced activation of the Janus kinase-signal
transducer and activator of transcription (JAK-STAT) signaling cascade
is essential for the induction of an antiviral state. Interference
of HDV with the JAK-STAT pathway could be responsible for the IFN-α
resistance in chronic hepatitis delta patients. We analyzed IFN-α–induced
signal transduction through the JAK-STAT pathway in human hepatoma
cells transfected with the complete HDV genome. The expression of
IFN-α–stimulated genes was investigated with reverse transcription
real-time polymerase chain reaction (PCR). STATs and JAKs activations
were examined by immunofluorescence and immunoblot. The IFN-α–stimulated
genes coding for the antiviral proteins myxovirus resistance A, double-stranded
RNA (dsRNA)-activated protein kinase and 2′,5′-oligoadenylate
synthetase were down-regulated in HDV-transfected hepatoma cells
in response to IFN-α treatment. HDV severely impaired the phosphorylation
of both STAT1 and STAT2, thus preventing their accumulation in the
nucleus. Furthermore, HDV blocked the IFN-α–stimulated tyrosine
phosphorylation of IFN receptor-associated JAK kinase Tyk2, without
affecting either the tyrosine phosphorylation of Jak1 or the expression
of type I IFN receptor subunits. Conclusions: IFN-α–induced intracellular
signaling is impaired in HDV-transfected human hepatoma cells. HDV
subverts the effect of IFN-α by blocking Tyk2 activation, thereby
resulting in selective impairment of activation and translocation
to the nucleus of STAT1 and STAT2. Interference of HDV with IFN-α
signaling could represent an important mechanism of viral persistence
and treatment resistance. (HEPATOLOGY 2008.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.22654}
}
@ARTICLE{Pugniere2011,
author = {Pascal Pugniere and Sebastien Banzet and Thomas Chaillou and Catherine
Mouret and Andre Peinnequin},
title = {Pitfalls of reverse transcription quantitative polymerase chain reaction
standardization: Volume-related inhibitors of reverse transcription},
journal = {Analytical Biochemistry},
year = {2011},
volume = {415},
pages = {151 - 157},
number = {2},
abstract = {A large part of the reliability of reverse transcription quantitative
polymerase chain reaction (RT-qPCR) data depends on technical variations.
Such variations are mainly attributable to the reverse transcription
step. Standardization is a key factor in decreasing the intersample
variability. However, an ideal standardization is not always possible,
and compromises must be found. Due to technical requirements, the
current consensus is that a constant amount of total RNA should be
used for the RT step (CA-RT). Because RNA isolation yields are variable,
such a practice requires the use of variable volumes of nucleic acid
extracts in RT reaction. We demonstrate that some RNA extracts contain
both exogenous and endogenous inhibitors. These inhibitors induce
a decrease in RT efficiency that significantly impairs the reliability
of RT-qPCR data. Conversely, these inhibitors have a slight effect
on the qPCR step. To overcome such drawbacks, we proposed to carry
out the RT reaction with a constant volume of RNA extract by preserving
a constant RNA amount through the supplementation of yeast transfer
RNA (CV-RT). We show that CV-RT, compared with the usual CA-RT, allows
us to decrease the RT-qPCR variability induced by intersample differences.
Such a decrease is a prerequisite for the reliability of messenger
RNA quantification.},
doi = {10.1016/j.ab.2011.04.008},
issn = {0003-2697},
keywords = {Reverse transcription},
url = {http://www.sciencedirect.com/science/article/pii/S0003269711002338}
}
@ARTICLE{Puig2010,
author = {Puig, Oscar and Wang, I-Ming and Cheng, Ping and Zhou, Pris and Roy,
Sophie and Cully, Doris and Peters, Mette and Benita, Yair and Thompson,
John and Cai, Tian-Quan},
title = {Transcriptome profiling and network analysis of genetically hypertensive
mice identifies potential pharmacological targets of hypertension},
journal = {Physiol Genomics},
year = {2010},
volume = {42A},
pages = {24--32},
number = {1},
month = sep,
abstract = {Hypertension is a condition with major cardiovascular and renal complications,
affecting nearly a billion patients worldwide. Few validated gene
targets are available for pharmacological intervention, so there
is a need to identify new biological pathways regulating blood pressure
and containing novel targets for treatment. The genetically hypertensive
"blood pressure high" (BPH), normotensive "blood pressure normal"
(BPN), and hypotensive "blood pressure low" (BPL) inbred mouse strains
are an ideal system to study differences in gene expression patterns
that may represent such biological pathways. We profiled gene expression
in liver, heart, kidney, and aorta from BPH, BPN, and BPL mice and
determined which biological processes are enriched in observed organ-specific
signatures. As a result, we identified multiple biological pathways
linked to blood pressure phenotype that could serve as a source of
candidate genes causal for hypertension. To distinguish in the kidney
signature genes whose differential expression pattern may cause changes
in blood pressure from those genes whose differential expression
pattern results from changes in blood pressure, we integrated phenotype-associated
genes into Genetic Bayesian networks. The integration of data from
gene expression profiling and genetics networks is a valuable approach
to identify novel potential targets for the pharmacological treatment
of hypertension.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42A/1/24}
}
@ARTICLE{Puig2011,
author = {Puig, Oscar and Yuan, Jeffrey and Stepaniants, Sergey and Zieba,
Renata and Zycband, Emanuel and Morris, Mark and Coulter, Silvija
and Yu, Xiang and Menke, John and Woods, John and Chen, Fabian and
Ramey, Dena R. and He, Xuanmin and O'Neill, Edward A. and Hailman,
Eric and Johns, Douglas G. and Hubbard, Brian K. and Yee Lum, Pek
and Wright, Samuel D. and DeSouza, Mary M. and Plump, Andrew and
Reiser, Vladimir},
title = {A Gene Expression Signature That Classifies Human Atherosclerotic
Plaque by Relative Inflammation Status},
journal = {Circ Cardiovasc Genet},
year = {2011},
volume = {4},
pages = {595-604},
number = {6},
abstract = {Background--Atherosclerosis is a complex disease requiring improvements
in diagnostic techniques and therapeutic treatments. Both improvements
will be facilitated by greater exploration of the biology of atherosclerotic
plaque. To this end, we carried out large-scale gene expression analysis
of human atherosclerotic lesions. Methods and Results--Whole genome
expression analysis of 101 plaques from patients with peripheral
artery disease identified a robust gene signature (1514 genes) that
is dominated by processes related to Toll-like receptor signaling,
T-cell activation, cholesterol efflux, oxidative stress response,
inflammatory cytokine production, vasoconstriction, and lysosomal
activity. Further analysis of gene expression in microdissected carotid
plaque samples revealed that this signature is differentially expressed
in macrophage-rich and smooth muscle cell-containing regions. A quantitative
PCR gene expression panel and inflammatory composite score were developed
on the basis of the atherosclerotic plaque gene signature. When applied
to serial sections of carotid plaque, the inflammatory composite
score was observed to correlate with histological and morphological
features related to plaque vulnerability. Conclusions--The robust
mRNA expression signature identified in the present report is associated
with pathological features of vulnerable atherosclerotic plaque and
may be useful as a source of biomarkers and targets of novel antiatherosclerotic
therapies.},
doi = {10.1161/CIRCGENETICS.111.960773},
eprint = {http://circgenetics.ahajournals.org/cgi/reprint/4/6/595.pdf},
url = {http://circgenetics.ahajournals.org/cgi/content/abstract/4/6/595}
}
@ARTICLE{Puig2004,
author = {Puig, Sergi and Lau, Miranda and Thiele, Dennis J.},
title = {Cti6 Is an Rpd3-Sin3 Histone Deacetylase-associated Protein Required
for Growth under Iron-limiting Conditions in Saccharomyces cerevisiae},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {30298--30306},
number = {29},
month = jul,
abstract = {Iron and copper are redox active metals essential for life. In the
budding yeast Saccharomyces cerevisiae, expression of iron and copper
genes involved in metal acquisition and utilization is tightly regulated
at the transcriptional level. In addition iron and copper metabolism
are inextricably linked because of the dependence on copper as a
co-factor for iron uptake or mobilization. To further identify genes
that function in iron and copper homeostasis, we screened for novel
yeast mutants defective for iron limiting growth and thereby identified
the CTI6 gene. Cti6 is a PHD finger-containing protein that has been
shown to participate in the interaction of the Ssn6-Tup1 co-repressor
with the Gcn5-containing SAGA chromatin-remodeling complex. In this
report we show that CTI6 mRNA levels are increased under iron-limiting
conditions, and that cti6 mutants display a growth defect under conditions
of iron deprivation. Furthermore, we demonstrate that Cti6 is a nuclear
protein that functionally associates with the Rpd3-Sin3 histone deacetylase
complex involved in transcriptional repression. Cti6 demonstrates
Rpd3-dependent transcriptional repression, and cti6 mutants exhibit
an enhanced silencing of telomeric, rDNA and HMR loci, similar to
mutants in genes encoding other Rpd3-Sin3-associated proteins. Microarray
experiments with cti6 mutants grown under iron-limiting conditions
show a down-regulation of telomeric genes and an up-regulation of
Aft1 and Tup1 target genes involved in iron and oxygen regulation.
Taken together, these data suggest a specific role for Cti6 in the
regulation of gene expression under conditions of iron limitation.},
url = {http://www.jbc.org/cgi/content/abstract/279/29/30298}
}
@ARTICLE{Puissegur2007,
author = {Puissegur, Marie-Pierre and Lay, Guillaume and Gilleron, Martine
and Botella, Laure and Nigou, Jerome and Marrakchi, Hedia and Mari,
Bernard and Duteyrat, Jean-Luc and Guerardel, Yann and Kremer, Laurent
and Barbry, Pascal and Puzo, Germain and Altare, Frederic},
title = {Mycobacterial Lipomannan Induces Granuloma Macrophage Fusion via
a TLR2-Dependent, ADAM9- and beta1 Integrin-Mediated Pathway},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {3161--3169},
number = {5},
month = mar,
abstract = {Tuberculous granulomas are the sites of interaction between the host
response and the tubercle bacilli within infected individuals. They
mainly consist of organized aggregations of lymphocytes and macrophages
(Mf). A predominant role of mycobacterial envelope glycolipids in
granulomas formation has been recently emphasized, yet the signaling
events interfering with granuloma cell differentiation remain elusive.
To decipher this molecular machinery, we have recently developed
an in vitro human model of mycobacterial granulomas. In this study,
we provide evidence that the mycobacterial proinflammatory phosphatidyl-myo-inositol
mannosides and lipomannans (LM), as well as the anti-inflammatory
lipoarabinomannan induce granuloma formation, yet only the proinflammatory
glycolipids induce the fusion of granuloma Mf into multinucleated
giant cells (MGC). We also demonstrate that LM induces large MGC
resembling those found in vivo within the granulomas of tuberculosis
patients, and that this process is mediated by TLR2 and is dependent
on the [beta]1 integrin/ADAM9 cell fusion machinery. Our results
demonstrate for the first time that the Mf differentiation stage
specifically occurring within granulomatous structures (i.e., MGC
formation) is triggered by mycobacterial envelope glycolipids, which
are capable of inducing the cell fusion machinery. This provides
the first characterization of the ontogeny of human granuloma MGC,
thus resulting in a direct modulation by a particular mycobacterial
envelope glycolipid of the differentiation process of granuloma Mf.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/5/3161}
}
@ARTICLE{Pujadas2010,
author = {Pujadas, Lluis and Gruart, Agnes and Bosch, Carles and Delgado, Lidia
and Teixeira, Catia M. and Rossi, Daniela and de Lecea, Luis and
Martinez, Albert and Delgado-Garcia, Jose M. and Soriano, Eduardo},
title = {Reelin Regulates Postnatal Neurogenesis and Enhances Spine Hypertrophy
and Long-Term Potentiation},
journal = {J. Neurosci.},
year = {2010},
volume = {30},
pages = {4636--4649},
number = {13},
month = mar,
abstract = {Reelin, an extracellular protein essential for neural migration and
lamination, is also expressed in the adult brain. To unravel the
function of this protein in the adult forebrain, we generated transgenic
mice that overexpress Reelin under the control of the CaMKII{alpha}
promoter. Overexpression of Reelin increased adult neurogenesis and
impaired the migration and positioning of adult-generated neurons.
In the hippocampus, the overexpression of Reelin resulted in an increase
in synaptic contacts and hypertrophy of dendritic spines. Induction
of long-term potentiation (LTP) in alert-behaving mice showed that
Reelin overexpression evokes a dramatic increase in LTP responses.
Hippocampal field EPSP during a classical conditioning paradigm was
also increased in these mice. Our results indicate that Reelin levels
in the adult brain regulate neurogenesis and migration, as well as
the structural and functional properties of synapses. These observations
suggest that Reelin controls developmental processes that remain
active in the adult brain.},
url = {http://www.jneurosci.org/cgi/content/abstract/30/13/4636}
}
@ARTICLE{Pukrop2010,
author = {Pukrop, Tobias and Dehghani, Faramarz and Chuang, Han-Ning. and Lohaus,
Raphaela and Bayanga, Kathrin and Heermann, Stephan and Regen, Tommy
and Rossum, Denise Van and Klemm, Florian and Schulz, Matthias and
Siam, Laila and Hoffmann, Anja and Trümper, Lorenz and Stadelmann,
Christine and Bechmann, Ingo and Hanisch, Uwe-Karsten and Binder,
Claudia},
title = {Microglia promote colonization of brain tissue by breast cancer cells
in a Wnt-dependent way},
journal = {Glia},
year = {2010},
volume = {58},
pages = {1477--1489},
number = {12},
abstract = {Abstract 10.1002/glia.21022.abs Although there is increasing evidence
that blood-derived macrophages support tumor progression, it is still
unclear whether specialized resident macrophages, such as brain microglia,
also play a prominent role in metastasis formation. Here, we show
that microglia enhance invasion and colonization of brain tissue
by breast cancer cells, serving both as active transporters and guiding
rails. This is antagonized by inactivation of microglia as well as
by the Wnt inhibitor Dickkopf-2. Proinvasive microglia demonstrate
altered morphology, but neither upregulation of M2-like cytokines
nor differential gene expression. Bacterial lipopolysacharide shifts
tumor-educated microglia into a classical M1 phenotype, reduces their
proinvasive function, and unmasks inflammatory and Wnt signaling
as the most strongly regulated pathways. Histological findings in
human brain metastases underline the significance of these results.
In conclusion, microglia are critical for the successful colonization
of the brain by epithelial cancer cells, suggesting inhibition of
proinvasive microglia as a promising antimetastatic strategy. ©
2010 Wiley-Liss, Inc.},
issn = {1098-1136},
keywords = {macrophages, seed and soil, tumor progression, carcinoma},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.21022}
}
@ARTICLE{Pulai2005,
author = {Pulai, Judit I. and Chen, Hong and Im, Hee-Jeong and Kumar, Sanjay
and Hanning, Charles and Hegde, Priti S. and Loeser, Richard F.},
title = {NF-{kappa}B Mediates the Stimulation of Cytokine and Chemokine Expression
by Human Articular Chondrocytes in Response to Fibronectin Fragments},
journal = {J. Immunol.},
year = {2005},
volume = {174},
pages = {5781--5788},
number = {9},
month = may,
abstract = {Fibronectin fragments (FN-f) that bind to the {alpha}5{beta}1 integrin
stimulate chondrocyte-mediated cartilage destruction and could play
an important role in the progression of arthritis. The objective
of this study was to identify potential cytokine mediators of cartilage
inflammation and destruction induced by FN-f and to investigate the
mechanism of their stimulation. Human articular chondrocytes, isolated
from normal ankle cartilage obtained from tissue donors, were treated
with a 110-kDa FN-f in serum-free culture, and expression of various
cytokine genes was analyzed by cDNA microarray and by a cytokine
protein array. Compared with untreated control cultures, stimulation
by FN-f resulted in a >2-fold increase in IL-6, IL-8, MCP-1, and
growth-related oncogene {beta} (GRO-{beta}). Constitutive and FN-f-inducible
expression of GRO-{alpha} and GRO-{gamma} were also noted by RT-PCR
and confirmed by immunoblotting. Previous reports of IL-1{beta} expression
induced by FN-f were also confirmed, while TNF expression was found
to be very low. Inhibitor studies revealed that FN-f-induced stimulation
of chondrocyte chemokine expression was dependent on NF-{kappa}B
activity, but independent of IL-1 autocrine signaling. The ability
of FN-f to stimulate chondrocyte expression of multiple proinflammatory
cytokines and chemokines suggests that damage to the cartilage matrix
is capable of inducing a proinflammatory state responsible for further
progressive matrix destruction, which also includes the chemoattraction
of inflammatory cells. Targeting the signaling pathways activated
by FN-f may be an effective means of inhibiting production of multiple
mediators of cartilage destruction.},
url = {http://www.jimmunol.org/cgi/content/abstract/174/9/5781}
}
@ARTICLE{Pulichino2008,
author = {Pulichino, Anne-Marie and Wang, I-Ming and Caron, Alexandre and Mortimer,
James and Auger, Anick and Boie, Yves and Elias, Jack A. and Kartono,
Aileen and Xu, Lijing and Menetski, Joseph and Sayegh, Camil E.},
title = {Identification of Transforming Growth Factor {beta}1-Driven Genetic
Programs of Acute Lung Fibrosis},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2008},
volume = {39},
pages = {324--336},
number = {3},
month = sep,
abstract = {Lung fibrosis is characterized by excessive accumulation of extracellular
matrix components leading to progressive airflow limitation. Distinct
profibrotic pathways converge on the activation of transforming growth
factor-{beta} (TGF-{beta}), a central growth factor implicated in
most fibroproliferative diseases. Recently, enforced expression of
bioactive human TGF-{beta}1 (hTGF-{beta}1) in lungs of transgenic
mice was shown to recapitulate several key pathophysiologies observed
in fibrotic disorders of the lung, including cellular inflammation,
tissue fibrosis, and myofibroblast hyperplasia. Inducible expression
of hTGF-{beta}1 in this system provided a unique opportunity to characterize
TGF-{beta}-driven mechanisms that precede and/or follow the onset
of inflammation and fibrosis. Using gene expression profiling in
lungs, we demonstrate temporal activation of key genetic programs
regulating cell movement and invasiveness, inflammation, organ remodeling,
and fibrosis. Consistent with our gene expression data, multiple
soluble mediators associated with inflammation and tissue remodeling
were markedly elevated in the bronchoalveolar lavage fluid of mice
expressing hTGF-{beta}1. We observe significant TGF-{beta}1-driven
infiltration of F4/80+ mononuclear cells producing bioactive arginase,
a marker of alternatively activated macrophages. Finally, we identified
a common "fibrosis" gene signature when comparing our findings with
published data derived from preclinical and clinical studies.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/39/3/324}
}
@ARTICLE{Pulkkinen2010,
author = {Pulkkinen, Ville and Bruce, Sara and Rintahaka, Johanna and Hodgson,
Ulla and Laitinen, Tarja and Alenius, Harri and Kinnula, Vuokko L.
and Myllarniemi, Marjukka and Matikainen, Sampsa and Kere, Juha},
title = {ELMOD2, a candidate gene for idiopathic pulmonary fibrosis, regulates
antiviral responses},
journal = {FASEB J},
year = {2010},
volume = {24},
pages = {1167--1177},
number = {4},
month = apr,
abstract = {Viral infections and abnormal host response are thought to cause epithelial
injury in idiopathic pulmonary fibrosis (IPF). To understand IPF
pathogenesis, we have used overexpression cell models and expression
microarrays to discover genes networked with ELMO domain containing
2 (ELMOD2) gene genetically implicated in IPF. The identified pathways
were confirmed in vitro, and ELMOD2 protein expression was characterized
in tissue samples. Here 303 genes were significantly altered after
ELMOD2 transfection of human alveolar epithelial A549 cell line.
The enriched pathways were interferon induction, viral response,
antigen processing and presentation, and I-/nuclear factor-{kappa}B
signaling. ELMOD2 showed immunoreactivity in macrophages and type
II alveolar epithelial cells in normal human lung. In A549 cells,
forced expression of ELMOD2 increased type I and type III interferon
mRNA expression, and ELMOD2-specific siRNA molecules inhibited expression
of these antiviral cytokines in response to Toll-like receptor three
(TLR3) activation. In human macrophages silencing of ELMOD2 inhibited
TLR3-dependent expression of type I and type III interferon genes.
Influenza A virus infection decreased ELMOD2 mRNA expression in A549
cells and macrophages suggesting negative regulation in viral infections.
In summary, our results show that TLR3 pathway is dependent on ELMOD2.--Pulkkinen,
V., Bruce, S., Rintahaka, J., Hodgson, U., Laitinen, T., Alenius,
H., Kinnula, V. L., Myllarniemi, M., Matikainen, S., Kere, J. ELMOD2,
a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral
responses.},
url = {http://www.fasebj.org/cgi/content/abstract/24/4/1167}
}
@ARTICLE{Pull2005,
author = {Pull, Sarah L. and Doherty, Jason M. and Mills, Jason C. and Gordon,
Jeffrey I. and Stappenbeck, Thaddeus S.},
title = {Activated macrophages are an adaptive element of the colonic epithelial
progenitor niche necessary for regenerative responses to injury},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {99--104},
number = {1},
month = jan,
abstract = {We have identified cellular and molecular features of the stem cell
niche required for marked amplification of mouse colonic epithelial
progenitors (ColEPs) that occurs in response to wounding of the epithelium
with dextran sodium sulfate. This regenerative response in areas
adjacent to breaches in the epithelial barrier depends on the gut
microbiota because ColEP proliferation is markedly diminished in
germ-free animals. Analysis of conventionally raised C57BL/6 (B6)
knockout mice lacking the Toll-like receptor signal transduction
pathway component Myd88 and wild-type animals transplanted with Myd88-/-
bone marrow, revealed that Myd88-mediated signaling through mesenchymal
cells is also required for the ColEP response. Studies of B6 Csf1op/op
(lacking macrophages) mice, Rag1-/- mice, and wild-type mice treated
with neutrophil-specific Gr1 mAbs, disclosed that macrophages but
not lymphocytes or neutrophils are necessary. GeneChip analysis of
laser-capture-microdissected mesenchymal cells coupled with immunohistochemical
and electron microscopic studies showed that, during the regenerative
response, macrophages in the pericryptal stem cell niche express
genes associated with their activation and extend processes to directly
contact ColEPs near the crypt base. GeneChip analysis also identified
a number of potential molecular mediators of regeneration expressed
in the pericryptal progenitor niche, including secreted factors that
stimulate epithelial proliferation and proteins involved in extracellular
matrix and basement membrane function, stability, and growth factor
binding. Together, these studies indicate that the colonic epithelial
progenitor niche is a dynamic structure in which macrophages function
as mobile "cellular transceivers" that coordinate inputs from luminal
microbes and injured epithelium and transmit regenerative signals
to neighboring ColEPs.},
url = {http://www.pnas.org/cgi/content/abstract/102/1/99}
}
@ARTICLE{Pulliam2004,
author = {Pulliam, Lynn and Sun, Bing and Rempel, Hans},
title = {Invasive chronic inflammatory monocyte phenotype in subjects with
high HIV-1 viral load},
journal = {Journal of Neuroimmunology},
year = {2004},
volume = {157},
pages = {93--98},
number = {1-2},
month = dec,
abstract = {Human immunodeficiency virus type 1 (HIV-1)-infected monocytes trafficking
into the central nervous system are a risk factor for HIV-1-associated
dementia. We performed global gene expression analysis on CD14+ monocytes
isolated from HIV-1-infected individuals and controls to identify
HIV-1-related changes in monocyte phenotype. Monocytes from subjects
with high viral load (HVL) had a significant increase in monocytes
expressing CD16, CCR5, and MCP-1. There was also an increase in sialoadhesin,
a macrophage marker of chronic inflammation. Expression of proinflammatory
cytokine genes IL-1, IL-6, and TNF-[alpha] was unchanged in individuals
with HIV-1 compared to control CD14+ monocytes. Differential gene
expression identified by DNA microarray analysis was confirmed with
reverse transcription polymerase chain reaction (RT-PCR), while increased
protein expression was characterized by immunofluorescence. We concluded
that there is a circulating CD14+ macrophage hybrid phenotype in
subjects with HVL.},
booktitle = {Molecular Markers and Mechanisms of HIV-Induced Nervous System Disease},
issn = {0165-5728},
keywords = {HIV, Monocyte, HAD, Sialoadhesin, Inflammation},
url = {http://www.sciencedirect.com/science/article/B6T03-4DN4JN2-1/2/7d5539d11561e97c5a696832eba5eb3c}
}
@ARTICLE{Pumphrey2009,
author = {Pumphrey, Michael and Bai, Jianfa and Laudencia-Chingcuanco, Debbie
and Anderson, Olin and Gill, Bikram S.},
title = {Nonadditive Expression of Homoeologous Genes Is Established Upon
Polyploidization in Hexaploid Wheat},
journal = {Genetics},
year = {2009},
volume = {181},
pages = {1147--1157},
number = {3},
month = mar,
abstract = {Effects of polyploidy in allohexaploid wheat (Triticum aestivum L.)
have primarily been ascribed to increases in coding sequence variation
and potential to acquire new gene functions through mutation of redundant
loci. However, regulatory variation that arises through new promoter
and transcription factor combinations or epigenetic events may also
contribute to the effects of polyploidization. In this study, gene
expression was characterized in a synthetic T. aestivum line and
the T. turgidum and Aegilops tauschii parents to establish a timeline
for such regulatory changes and estimate the frequency of nonadditive
expression of homoeologous transcripts in newly formed T. aestivum.
Large-scale analysis of nonadditive gene expression was assayed by
microarray expression experiments, where synthetic T. aestivum gene
expression was compared to additive model values (mid-parent) calculated
from parental T. turgidum and Ae. tauschii expression levels. Approximately
16% of genes were estimated to display nonadditive expression in
synthetic T. aestivum. A certain fraction of the genes (2.9%) showed
overdominance or underdominance. cDNA-single strand conformation
polymorphism analysis was applied to measure expression of homoeologous
transcripts and further verify microarray data. The results demonstrate
that allopolyploidization, per se, results in rapid initiation of
differential expression of homoeologous loci and nonadditive gene
expression in T. aestivum.},
url = {http://www.genetics.org/cgi/content/abstract/181/3/1147}
}
@ARTICLE{Punzo2007,
author = {Punzo, Claudio and Cepko, Constance},
title = {Cellular Responses to Photoreceptor Death in the rd1 Mouse Model
of Retinal Degeneration},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {849--857},
number = {2},
month = feb,
abstract = {PURPOSE. Retinal degeneration is a disease that typically involves
the loss of photoreceptors. Murine models have been established for
such degenerations, and a variety of methods have been used to follow
the progression of the disease. In the present study in situ hybridization
was used to analyze gene expression responses in the different retinal
cell types during the period of cone death in the rd1 mouse model.
METHODS. A preliminary microarray analysis led to the selection of
169 candidate genes that might change in level of expression during
degeneration. Probes corresponding to these genes were used for in
situ hybridization on tissue during the period of cone death. Expression
values were assigned to the intensities of in situ hybridization
signals and were compared between mutant and wild-type tissue. RESULTS.
During the peak of cone death, the in situ hybridization signals
were typically higher in the mutant. This signal change was often
true of genes with a wild-type pattern of expression in ganglion
cells, bipolar cells, and/or Muller glia. In such cases, the upregulation
was highest in bipolar cells and/or Muller glia. CONCLUSIONS. All
retinal cell types responded during the process of retinal degeneration,
as revealed by changes in gene expression. Genes that showed changes
in the in situ hybridization signals during the period of cone death
were typically higher in the mutant, with many of them expressed
in both the ganglion cell layer and the inner nuclear layer.},
url = {http://www.iovs.org/cgi/content/abstract/48/2/849}
}
@ARTICLE{Purbey2009,
author = {Purbey, Prabhat Kumar and Singh, Sunita and Notani, Dimple and Kumar,
P. Pavan and Limaye, Amita S. and Galande, Sanjeev},
title = {Acetylation-Dependent Interaction of SATB1 and CtBP1 Mediates Transcriptional
Repression by SATB1},
journal = {Mol. Cell. Biol.},
year = {2009},
volume = {29},
pages = {1321--1337},
number = {5},
month = mar,
abstract = {Special AT-rich binding protein 1 (SATB1) acts as a global regulator
of gene expression by recruiting various corepressor or coactivator
complexes, thereby establishing a unique chromatin structure at its
genomic targets in a context-dependent manner. Although SATB1 acts
predominantly as a repressor via recruitment of histone deacetylase
1 (HDAC1) complexes, the precise mechanism of global repression is
not clear. Here we report that SATB1 and C-terminal binding protein
1 (CtBP1) form a repressor complex in vivo. The interaction occurs
via the CtBP1 interaction consensus motif PVPLS within the PDZ-like
domain of SATB1. The acetylation of SATB1 upon LiCl and ionomycin
treatments disrupts its association with CtBP1, resulting in enhanced
target gene expression. Chromatin immunoprecipitation analysis indicated
that the occupancy of CtBP1 and HDAC1 is gradually decreased and
the occupancy of PCAF is elevated at the SATB1 binding sites within
the human interleukin-2 and mouse c-Myc promoters. Moreover, gene
expression profiling studies using cells in which expression of SATB1
and CtBP1 was silenced indicated commonly targeted genes that may
be coordinately repressed by the SATB1-CtBP1 complex. Collectively,
these results provide a mechanistic insight into the role of SATB1-CtBP1
interaction in the repression and derepression of SATB1 target genes
during Wnt signaling in T cells.},
url = {http://mcb.asm.org/cgi/content/abstract/29/5/1321}
}
@ARTICLE{Purcell2011,
author = {Purcell, Maureen K. and Marjara, Inderjit Singh and Batts, William
and Kurath, Gael and Hansen, John D.},
title = {Transcriptome analysis of rainbow trout infected with high and low
virulence strains of Infectious hematopoietic necrosis virus},
journal = {Fish \& Shellfish Immunology},
year = {2011},
volume = {30},
pages = {84--93},
number = {1},
month = jan,
abstract = {There are three main genetic lineages or genogroups of Infectious
hematopoietic necrosis virus (IHNV) in N. America. Strains representing
the M genogroup are more virulent in rainbow trout relative to the
U genogroup. In this study, we used microarray analysis to evaluate
potential mechanisms responsible for host-specific virulence in rainbow
trout that were given intraperitoneal injections of buffer or a representative
M or U type virus strain. Reverse transcriptase quantitative PCR
(RT-qPCR) was used to assess viral load and gene expression of select
immune genes. Viral load was significantly higher in trout infected
with the M virus starting at 24 h post-infection (p.i.) and continuing
until 72 h p.i. Microarray analysis of the 48 h time point revealed
153 up-regulated and 248 down-regulated features in response to M
virus infection but only 62 up-regulated and 49 down-regulated features
following U virus infection. Translation and transcription features
were among the most frequent down-regulated features in response
to M virus infection and may be associated with the host cell shutoff
phenomenon. A greater host cell shutoff response by the M virus may
facilitate subversion of the host cell transcriptional machinery
and enhance viral replication, suggesting the M virus may be better
optimized to manipulate the rainbow trout transcriptional and translational
machinery. Anti-viral associated features were the most commonly
up-regulated features. A common set of features were up-regulated
in both the M and U infection groups, but were induced to a higher
magnitude in the M infection group. Gene expression of the anti-viral
genes Mx-1 and Vig-1 was correlated but not entirely dependent on
viral load in the anterior kidney. Slower replication of the U virus
may allow the host more time to induce protective anti-viral immune
mechanisms.},
issn = {1050-4648},
keywords = {Microarray, Gene expression, Interferon, Translation, Transcription,
Host cell shutoff},
url = {http://www.sciencedirect.com/science/article/pii/S1050464810002949}
}
@ARTICLE{Purcell2006,
author = {Purcell, Maureen K. and Nichols, Krista M. and Winton, James R. and
Kurath, Gael and Thorgaard, Gary H. and Wheeler, Paul and Hansen,
John D. and Herwig, Russell P. and Park, Linda K.},
title = {Comprehensive gene expression profiling following DNA vaccination
of rainbow trout against infectious hematopoietic necrosis virus},
journal = {Molecular Immunology},
year = {2006},
volume = {43},
pages = {2089--2106},
number = {13},
month = may,
abstract = {The DNA vaccine based on the glycoprotein gene of Infectious hematopoietic
necrosis virus induces a non-specific anti-viral immune response
and long-term specific immunity against IHNV. This study characterized
gene expression responses associated with the early anti-viral response.
Homozygous rainbow trout were injected intra-muscularly (I.M.) with
vector DNA or the IHNV DNA vaccine. Gene expression in muscle tissue
(I.M. site) was evaluated using a 16,008 feature salmon cDNA microarray.
Eighty different genes were significantly modulated in the vector
DNA group while 910 genes were modulated in the IHNV DNA vaccinate
group relative to control group. Quantitative reverse-transcriptase
PCR was used to examine expression of selected immune genes at the
I.M. site and in other secondary tissues. In the localized response
(I.M. site), the magnitudes of gene expression changes were much
greater in the vaccinate group relative to the vector DNA group for
the majority of genes analyzed. At secondary systemic sites (e.g.
gill, kidney and spleen), type I IFN-related genes were up-regulated
in only the IHNV DNA vaccinated group. The results presented here
suggest that the IHNV DNA vaccine induces up-regulation of the type
I IFN system across multiple tissues, which is the functional basis
of early anti-viral immunity.},
issn = {0161-5890},
keywords = {Plasmid DNA, Vaccine, Interferon, Microarray, Quantitative PCR},
url = {http://www.sciencedirect.com/science/article/B6T9R-4J2KRN7-1/2/c6b5c3cf1c82915c5047c771d72d336c}
}
@ARTICLE{Purdie2012,
author = {Auriol C. Purdie and Karren M. Plain and Douglas J. Begg and Kumudika
de Silva and Richard J. Whittington},
title = {Expression of genes associated with the antigen presentation and
processing pathway are consistently regulated in early Mycobacterium
avium subsp. paratuberculosis infection},
journal = {Comparative Immunology, Microbiology and Infectious Diseases},
year = {2012},
pages = { - },
number = {0},
abstract = {The primary objective of this study was to evaluate early gene expression
profiles associated with paratuberculosis in cattle exposed to known
infectious doses of Mycobacterium avium sub-species paratuberculosis
(MAP). A Johne's disease experimental infection field trial was conducted
on a mixed population of Holstein and Holstein Red cattle. Blood
samples from four MAP exposed and four unexposed cattle, selected
based on IFNγ expressions were taken at 9, 13 and 21 weeks and RNA
processed to Affymetrix GeneChipâ„¢ Bovine Genome arrays. Ontological
analysis revealed consistent differences in gene expression between
MAP exposed and control animals. A stark variation was observed in
expression of a number of genes along antigen presentation pathways,
suggesting that MAP exposure potentially results in the host immune
response switching to a CD8+ biased antigen presentation profile.
This requires further in-depth analysis since it exposes a hitherto
unconfirmed association between MAP exposure and in vivo MHC gene
modulation.},
doi = {10.1016/j.cimid.2011.12.007},
issn = {0147-9571},
keywords = {Johne's disease},
url = {http://www.sciencedirect.com/science/article/pii/S0147957111001263}
}
@ARTICLE{Puri2011,
author = {Puri, Jyoti and Bellinger, Larry L. and Kramer, Phillip R.},
title = {Estrogen in cycling rats alters gene expression in the temporomandibular
joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper
cervical cord junction},
journal = {Journal of Cellular Physiology},
year = {2011},
volume = {226},
pages = {3169--3180},
number = {12},
abstract = {Females report temporomandibular joint (TMJ) pain more than men and
studies suggest estrogen modulates this pain response. Our goal in
this study was to determine genes that are modulated by physiological
levels of 17β-estradiol that could have a role in TMJ pain. To complete
this goal, saline or complete Freund's adjuvant was injected in the
TMJ when plasma 17β-estradiol was low or when it was at a high proestrus
level. TMJ, trigeminal ganglion, and trigeminal subnucleus caudalis/upper
cervical cord junction (Vc/C1–2) tissues were isolated from the
treated rats and expression of 184 genes was quantitated in each
tissue using real-time PCR. Significant changes in the amount of
specific transcripts were observed in the TMJ tissues, trigeminal
ganglia, and Vc/C1–2 region when comparing rats with high and low
estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor
α2 (Glra2) were two genes of interest because of their direct function
in neuronal activity and a >29-fold increase in the trigeminal ganglia
was observed in proestrus rats with TMJ inflammation. Immunohistochemical
studies showed that Gabrα6 and Glrα2 neuronal and not glial expression
increased when comparing rats with high and low estrogen. Estrogen
receptors α and β are present in neurons of the trigeminal ganglia,
whereby 17β-estradiol can alter expression of Gabrα6 and Glrα2.
Also, estrogen receptor α (ERα) but not ERβ was observed in satellite
glial cells of the trigeminal ganglia. These results demonstrate
that genes associated with neurogenic inflammation or neuronal excitability
were altered by changes in the concentration of 17β-estradiol. J.
Cell. Physiol. 226: 3169–3180, 2011. © 2011 Wiley Periodicals,
Inc.},
doi = {10.1002/jcp.22671},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22671}
}
@ARTICLE{Pusapati2010,
author = {Pusapati, Raju V. and Weaks, Regina L. and Rounbehler, Robert J.
and McArthur, Mark J. and Johnson, David G.},
title = {E2F2 suppresses Myc-induced proliferation and tumorigenesis},
journal = {Mol. Carcinog.},
year = {2010},
volume = {49},
pages = {152--156},
number = {2},
abstract = {Abstract 10.1002/mc.20584.abs Deregulation of E2F transcriptional
activity as a result of alterations in the p16-cyclin D-Rb pathway
is a hallmark of cancer. However, the roles of the different E2F
family members in the process of tumorigenesis are still being elucidated.
Studies in mice and humans suggest that E2F2 functions as a tumor
suppressor. Here we demonstrate that E2f2 inactivation cooperates
with transgenic expression of Myc to enhance tumor development in
the skin and oral cavity. In fact, hemizygosity at the E2f2 locus
was sufficient to increase tumor incidence in this model. Loss of
E2F2 enhanced proliferation in Myc transgenic tissue but did not
affect Myc-induced apoptosis. E2F2 did not behave as a simple activator
of transcription in epidermal keratinocytes but instead appeared
to differentially regulate gene expression dependent on the individual
target. E2f2 inactivation also altered the changes in gene expression
in Myc transgenic cells by enhancing the increase of some genes,
such as cyclin E, and reversing the repression of other genes. These
findings demonstrate that E2F2 can function as a tumor suppressor
in epithelial tissues, perhaps by limiting proliferation in response
to Myc. © 2009 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {E2F, Myc, oral squamous cell carcinoma},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20584}
}
@ARTICLE{Pushalkar2011,
author = {Pushalkar, Smruti and Mane, Shrinivasrao P. and Ji, Xiaojie and Li,
Yihong and Evans, Clive and Crasta, Oswald R. and Morse, Douglas
and Meagher, Robert and Singh, Anup and Saxena, Deepak},
title = {Microbial diversity in saliva of oral squamous cell carcinoma},
journal = {FEMS Immunology \& Medical Microbiology},
year = {2011},
volume = {61},
pages = {269--277},
number = {3},
abstract = {Abstract In the oral cavity, chronic inflammation has been observed
at various stages of oral squamous cell carcinomas (OSCC). Such inflammation
could result from persistent mucosal or epithelial cell colonization
by microorganisms. There is increasing evidence of the involvement
of oral bacteria in inflammation, warranting further studies on the
association of bacteria with the progression of OSCC. The objective
of this study was to evaluate the diversity and relative abundance
of bacteria in the saliva of subjects with OSCC. Using 454 parallel
DNA sequencing, ∼58 000 PCR amplicons that span the V4–V5 hypervariable
region of rRNAs from five subjects were sequenced. Members of eight
phyla (divisions) of bacteria were detected. The majority of classified
sequences belonged to the phyla Firmicutes (45%) and Bacteroidetes
(25%). Further, 52 different genera containing approximately 860
(16.51%) known species were identified and 1077 (67%) sequences belonging
to various uncultured bacteria or unclassified groups. The species
diversity estimates obtained with abundance-based coverage estimators
and Chao1 were greater than published analyses of other microbial
profiles from the oral cavity. Fifteen unique phylotypes were present
in all three OSCC subjects.},
doi = {10.1111/j.1574-695X.2010.00773.x},
issn = {1574-695X},
keywords = {oral squamous cell carcinoma, microbial diversity, denaturing gradient
gel electrophoresis, 454 pyrosequencing},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-695X.2010.00773.x}
}
@ARTICLE{Pusztai2003,
author = {Pusztai, Lajos and Ayers, Mark and Stec, James and Clark, Edward
and Hess, Kenneth and Stivers, David and Damokosh, Andrew and Sneige,
Nour and Buchholz, Thomas A. and Esteva, Francisco J. and Arun, Banu
and Cristofanilli, Massimo and Booser, Daniel and Rosales, Marguerite
and Valero, Vicente and Adams, Constantine and Hortobagyi, Gabriel
N. and Symmans, W. Fraser},
title = {Gene Expression Profiles Obtained from Fine-Needle Aspirations of
Breast Cancer Reliably Identify Routine Prognostic Markers and Reveal
Large-Scale Molecular Differences between Estrogen-negative and Estrogen-positive
Tumors},
journal = {Clin. Cancer Res.},
year = {2003},
volume = {9},
pages = {2406--2415},
number = {7},
month = jul,
abstract = {Purpose: The purpose of this study was to determine whether comprehensive
transcriptional profiles (TPs) can be obtained from single-passage
fine-needle aspirations (FNAs) of breast cancer and to explore whether
profiles capture routine clinicopathological parameters. Experimental
Design: Expression profiles were available on 38 patients with stage
I-III breast cancer who underwent FNA at the time of diagnosis. [33P]dCTP-labeled
cDNA probes were generated and hybridized to cDNA membrane microarrays
that contained 30,000 human sequence clones, including 10,890 expressed
sequence tags. Results: The median total RNA yield from the biopsies
was 2 {micro}g (range, 1-25 {micro}g). The cellular composition of
each biopsy was examined and, on average,, 79% of the cells were
cancer cells. TP was successfully performed on all 38 of the biopsies.
Unsupervised complete-linkage hierarchical clustering with all of
the biopsies revealed an association between estrogen receptor (ER)
status and gene expression profiles. There was a strong correlation
between ER status determined by TP and measured by routine immunohistochemistry
(P = 0.001). A similar strong correlation was seen with HER-2 status
determined by fluorescent in situ hybridization (P = 0.0002). Using
the first 18 cases as the discovery set, we established a cutoff
of 2.0 and 18.0 for ER and HER-2 mRNA levels, respectively, to distinguish
clinically-negative from -positive cases. We also identified 105
genes (excluding the ER gene) the expression of which correlated
highly with clinical ER status. Twenty tumors were used for prospective
validation. HER-2 status was correctly identified in all 20 of the
cases, based on HER-2 mRNA content detected by TP. ER status was
correctly identified in 19 of 20 cases. When the marker set of 105
genes was used to prospectively predict ER status, TP-based classification
correctly identified 9 of 10 of the ER-positive and 7 of 10 of the
ER-negative tumors. We also explored supervised cluster analysis
using various functional categories of genes, and we observed a clear
separation between ER-negative and ER-positive tumors when genes
involved in signal transduction were used for clustering. Conclusions:
These results demonstrate that comprehensive TP can be performed
on FNA biopsies. TPs reliably measure conventional single-gene prognostic
markers such as ER and HER-2. A complex pattern of genes (not including
ER) can also be used to predict clinical ER status. These results
demonstrate that needle biopsy-based diagnostic microarray tests
may be developed that could capture conventional prognostic information
but may also contain additional clinical information that cannot
currently be measured with other methods.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/9/7/2406}
}
@ARTICLE{Puthawala2008,
author = {Puthawala, Khalid and Hadjiangelis, Nicos and Jacoby, Steven C. and
Bayongan, Emmanuel and Zhao, Zhicheng and Yang, Zhiwei and Devitt,
Mary Louise and Horan, Gerald S. and Weinreb, Paul H. and Lukashev,
Matvey E. and Violette, Shelia M. and Grant, Kristen S. and Colarossi,
Cristina and Formenti, Silvia C. and Munger, John S.},
title = {Inhibition of Integrin {alpha}v 6, an Activator of Latent Transforming
Growth Factor- , Prevents Radiation-induced Lung Fibrosis},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2008},
volume = {177},
pages = {82--90},
number = {1},
month = jan,
abstract = {Rationale: In experimental models, lung fibrosis is dependent on transforming
growth factor (TGF)-{beta} signaling. TGF-{beta} is secreted in a
latent complex with its propeptide, and TGF-{beta} activators release
TGF-{beta} from this complex. Because the integrin {alpha}v{beta}6
is a major TGF-{beta} activator in the lung, inhibition of {alpha}v{beta}6-mediated
TGF-{beta} activation is a logical strategy to treat lung fibrosis.
Objectives: To determine, by genetic and pharmacologic approaches,
whether murine radiation-induced lung fibrosis is dependent on {alpha}v{beta}6.
Methods: Wild-type mice, {alpha}v{beta}6-deficient (Itgb6-/-) mice,
and mice heterozygous for a Tgfb1 mutation that eliminates integrin-mediated
activation (Tgfb1+/RGE) were exposed to 14 Gy thoracic radiation.
Some mice were treated with an anti-{alpha}v{beta}6 monoclonal antibody
or a soluble TGF-{beta} receptor fusion protein. {alpha}v{beta}6
expression was determined by immunohistochemistry. Fibrosis, inflammation,
and gene expression patterns were assessed 20-32 weeks postirradiation.
Measurements and Main Results: {beta}6 Integrin expression increased
within the alveolar epithelium 18 weeks postirradiation, just before
onset of fibrosis. Itgb6-/- mice were completely protected from fibrosis,
but not from late radiation-induced mortality. Anti-{alpha}v{beta}6
therapy (1-10 mg/kg/wk) prevented fibrosis, but only higher doses
(6-10 mg/kg/wk) caused lung inflammation similar to that in Itgb6-/-
mice. Tgfb1-haploinsufficient mice were also protected from fibrosis.
Conclusions: {alpha}v{beta}6-Mediated TGF-{beta} activation is required
for radiation-induced lung fibrosis. Together with previous data,
our results demonstrate a robust requirement for {alpha}v{beta}6
in distinct fibrosis models. Inhibition of {alpha}v{beta}6-mediated
TGF-{beta} activation is a promising new approach for antifibrosis
therapy.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/177/1/82}
}
@ARTICLE{Putoux2011,
author = {Putoux, Audrey and Thomas, Sophie and Coene, Karlien L M and Davis,
Erica E and Alanay, Yasemin and Ogur, Gonul and Uz, Elif and Buzas,
Daniela and Gomes, Celine and Patrier, Sophie and Bennett, Christopher
L and Elkhartoufi, Nadia and Frison, Marie-Helene Saint and Rigonnot,
Luc and Joye, Nicole and Pruvost, Solenn and Utine, Gulen Eda and
Boduroglu, Koray and Nitschke, Patrick and Fertitta, Laura and Thauvin-Robinet,
Christel and Munnich, Arnold and Cormier-Daire, Valerie and Hennekam,
Raoul and Colin, Estelle and Akarsu, Nurten Ayse and Bole-Feysot,
Christine and Cagnard, Nicolas and Schmitt, Alain and Goudin, Nicolas
and Lyonnet, Stanislas and Encha-Razavi, Ferechte and Siffroi, Jean-Pierre
and Winey, Mark and Katsanis, Nicholas and Gonzales, Marie and Vekemans,
Michel and Beales, Philip L and Attie-Bitach, Tania},
title = {KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes},
journal = {Nat Genet},
year = {2011},
volume = {advance online publication},
pages = {--},
month = may,
comment = {10.1038/ng.826},
issn = {1546-1718},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/ng.826}
}
@ARTICLE{Puttikamonkul2010,
author = {Puttikamonkul, Srisombat and Willger, Sven D. and Grahl, Nora and
Perfect, John R. and Movahed, Navid and Bothner, Brian and Park,
Steven and Paderu, Padmaja and Perlin, David S. and Cramer Jr, Robert
A.},
title = {Trehalose 6-phosphate phosphatase is required for cell wall integrity
and fungal virulence but not trehalose biosynthesis in the human
fungal pathogen Aspergillus fumigatus},
journal = {Molecular Microbiology},
year = {2010},
volume = {77},
pages = {891--911},
number = {4},
abstract = {Summary The trehalose biosynthesis pathway is critical for virulence
in human and plant fungal pathogens. In this study, we tested the
hypothesis that trehalose 6-phosphate phosphatase (T6PP) is required
for Aspergillus fumigatus virulence. A mutant of the A. fumigatus
T6PP, OrlA, displayed severe morphological defects related to asexual
reproduction when grown on glucose (1%) minimal media. These defects
could be rescued by addition of osmotic stabilizers, reduction in
incubation temperature or increase in glucose levels (>Â 4%). Subsequent
examination of the mutant with cell wall perturbing agents revealed
a link between cell wall biosynthesis and trehalose 6-phosphate (T6P)
levels. As expected, high levels of T6P accumulated in the absence
of OrlA resulting in depletion of free inorganic phosphate and inhibition
of hexokinase activity. Surprisingly, trehalose production persisted
in the absence of OrlA. Further analyses revealed that A. fumigatus
contains two trehalose phosphorylases that may be responsible for
trehalose production in the absence of OrlA. Despite a normal growth
rate under in vitro growth conditions, the orlA mutant was virtually
avirulent in two distinct murine models of invasive pulmonary aspergillosis.
Our results suggest that further study of this pathway will lead
to new insights into regulation of fungal cell wall biosynthesis
and virulence.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07254.x}
}
@ARTICLE{Pycke2010,
author = {Pycke, Benny F. G. and Vanermen, Guido and Monsieurs, Pieter and
De Wever, Heleen and Mergeay, Max and Verstraete, Willy and Leys,
Natalie},
title = {Toxicogenomic Response of Rhodospirillum rubrum S1H to the Micropollutant
Triclosan},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {3503--3513},
number = {11},
month = jun,
abstract = {In the framework of the Micro-Ecological Life Support System Alternative
(MELiSSA) project, a pilot study was performed to identify the effects
of triclosan on the MELiSSA carbon-mineralizing microorganism Rhodospirillum
rubrum S1H. Triclosan is a biocide that is commonly found in human
excrement and is considered an emerging pollutant in wastewater and
the environment. Chronic exposure to MELiSSA-relevant concentrations
([≥]25 {micro}g liter-1) of triclosan resulted in a significant
extension of the lag phase of this organism but hardly affected the
growth rate. Analytical determinations gave no indication of triclosan
biodegradation during the growth experiment, and flow cytometric
viability analyses revealed that triclosan is bacteriostatic and
only slightly toxic to R. rubrum S1H. Using microarray analyses,
the genetic mechanisms supporting the reversibility of triclosan-induced
inhibition were scrutinized. An extremely triclosan-responsive cluster
of four small adjacent genes was identified, for which there was
up to 34-fold induction with 25 {micro}g liter-1 triclosan. These
four genes, for which the designation muf (micropollutant-upregulated
factor) is proposed, appear to be unique to R. rubrum and are shown
here for the first time to be involved in the response to stress.
Moreover, numerous other systems that are associated with the proton
motive force were shown to be responsive to triclosan, but they were
never as highly upregulated as the muf genes. In response to triclosan,
R. rubrum S1H induced transcription of the phage shock protein operon
(pspABC), numerous efflux systems, cell envelope consolidation mechanisms,
the oxidative stress response, beta-oxidation, and carbonic anhydrase,
while there was downregulation of bacterial conjugation and carboxysome
synthesis genes. The muf genes and three efflux-related genes showed
the most potential to be low-dose biomarkers.},
url = {http://aem.asm.org/cgi/content/abstract/76/11/3503}
}
@ARTICLE{Pyhtila2008,
author = {Pyhtila, Brook and Zheng, Tianli and Lager, Patrick J. and Keene,
Jack D. and Reedy, Mary C. and Nicchitta, Christopher V.},
title = {Signal sequence- and translation-independent mRNA localization to
the endoplasmic reticulum},
journal = {RNA},
year = {2008},
volume = {14},
pages = {445--453},
number = {3},
month = mar,
abstract = {The process of mRNA localization typically utilizes cis-targeting
elements and trans-recognition factors to direct the compartmental
organization of translationally suppressed mRNAs. mRNA localization
to the endoplasmic reticulum (ER), in contrast, occurs via a co-translational,
signal sequence/signal recognition particle (SRP)-dependent mechanism.
We have utilized cell fractionation/cDNA microarray analysis, shRNA-mediated
suppression of SRP expression, and mRNA reporter construct studies
to define the role of the SRP pathway in ER-directed mRNA localization.
Cell fractionation studies of mRNA partitioning between the cytosol
and ER demonstrated the expected enrichment of cytosolic/nucleoplasmic
protein-encoding mRNAs and secretory/integral membrane protein-encoding
mRNAs in the cytosol and ER fractions, respectively, and identified
a subpopulation of cytosolic/nucleoplasmic protein-encoding mRNAs
in the membrane-bound mRNA pool. The latter finding suggests a signal
sequence-independent pathway of ER-directed mRNA localization. Extending
from these findings, mRNA partitioning was examined in stable SRP54
shRNA knockdown HeLa cell lines. shRNA-directed reductions in SRP
did not globally alter mRNA partitioning patterns, although defects
in membrane protein processing were observed, further suggesting
the existence of multiple pathways for mRNA localization to the ER.
ER localization of GRP94-encoding mRNA was observed when translation
was disabled by mutation of the start codon/insertion of a 5'UTR
stem-loop structure or upon deletion of the encoded signal sequence.
Combined, these data indicate that the mRNA localization to the ER
can be conferred independent of the signal sequence/SRP pathway and
suggest that mRNA localization to the ER may utilize cis-encoded
targeting information.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/14/3/445}
}
@ARTICLE{Pyott2007,
author = {Pyott, Sonja J. and Meredith, Andrea L. and Fodor, Anthony A. and
Vazquez, Ana E. and Yamoah, Ebenezer N. and Aldrich, Richard W.},
title = {Cochlear Function in Mice Lacking the BK Channel {alpha}, beta1,
or beta4 Subunits},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {3312--3324},
number = {5},
month = feb,
abstract = {Large conductance voltage- and calcium-activated potassium (BK) channels
are important for regulating many essential cellular functions, from
neuronal action potential shape and firing rate to smooth muscle
contractility. In amphibians, reptiles, and birds, BK channels mediate
the intrinsic frequency tuning of the cochlear hair cell by an electrical
resonance mechanism. In contrast, inner hair cells of the mammalian
cochlea are extrinsically tuned by accessory structures of the cochlea.
Nevertheless, BK channels are present in inner hair cells and encode
a fast activating outward current. To understand the role of the
BK channel {alpha} and [beta] subunits in mammalian inner hair cells,
we analyzed the morphology, physiology, and function of these cells
from mice lacking the BK channel {alpha} (Slo-/-) and also the [beta]1
and [beta]4 subunits ([beta]1/4-/-). [beta]1/4-/- mice showed normal
subcellular localization, developmental acquisition, and expression
of BK channels. [beta]1/4-/- mice showed normal cochlear function
as indicated by normal auditory brainstem responses and distortion
product otoacoustic emissions. Slo-/- mice also showed normal cochlear
function despite the absence of the BK{alpha} subunit and the absence
of fast activating outward current from the inner hair cells. Moreover,
microarray analyses revealed no compensatory changes in transcripts
encoding ion channels or transporters in the cochlea from Slo-/-
mice. Slo-/- mice did, however, show increased resistance to noise-induced
hearing loss. These findings reveal the fundamentally different contribution
of BK channels to nonmammalian and mammalian hearing and suggest
that BK channels should be considered a target in the prevention
of noise-induced hearing loss.},
url = {http://www.jbc.org/cgi/content/abstract/282/5/3312}
}
@ARTICLE{PA©rez-Berezo2011,
author = {Teresa Pérez-Berezo and Angels Franch and Cristina Castellote and
Margarida Castell and Francisco J. Pérez-Cano},
title = {Mechanisms involved in down-regulation of intestinal IgA in rats
by high cocoa intake},
journal = {The Journal of Nutritional Biochemistry},
year = {2011},
pages = { - },
number = {0},
abstract = {Previous studies have shown that rat intestinal immunoglobulin A (IgA)
concentration and lymphocyte composition of the intestinal immune
system were influenced by a highly enriched cocoa diet. The aim of
this study was to dissect the mechanisms by which a long-term high
cocoa intake was capable of modifying gut secretory IgA in Wistar
rats. After 7 weeks of nutritional intervention, Peyer's patches,
mesenteric lymph nodes and the small intestine were excised for gene
expression assessment of IgA, transforming growth factor β, C-C
chemokine receptor-9 (CCR9), interleukin (IL)-6, CD40, retinoic acid
receptors (RARα and RARβ), C-C chemokine ligand (CCL)-25 and CCL28
chemokines, polymeric immunoglobulin receptor and toll-like receptors
(TLR) expression by real-time polymerase chain reaction. As in previous
studies, secretory IgA concentration decreased in intestinal wash
and fecal samples after cocoa intake. Results from the gene expression
showed that cocoa intake reduced IgA and IL‑6 in Peyer's patches
and mesenteric lymph nodes, whereas in small intestine, cocoa decreased
IgA, CCR9, CCL28, RARα and RARβ. Moreover, cocoa-fed animals presented
an altered TLR expression pattern in the three compartments studied.
In conclusion, a high-cocoa diet down-regulated cytokines such as
IL-6, which is required for the activation of B cells to become IgA-secreting
cells, chemokines and chemokine receptors, such as CCL28 and CCR9
together with RARα and RARβ, which are involved in the gut homing
of IgA-secreting cells. Moreover, cocoa modified the cross-talk between
microbiota and intestinal cells as was detected by an altered TLR
pattern. These overall effects in the intestine may explain the intestinal
IgA down-regulatory effect after the consumption of a long-term cocoa-enriched
diet.},
doi = {10.1016/j.jnutbio.2011.04.008},
issn = {0955-2863},
keywords = {Gut immune system},
url = {http://www.sciencedirect.com/science/article/pii/S0955286311001355}
}
@ARTICLE{PA©rez-Novo2010,
author = {Pérez-Novo, C. A. and Holtappels, G. and Vinall, S. L. and Xue,
L. and Zhang, N. and Bachert, C. and Pettipher, R.},
title = {CRTH2 mediates the activation of human Th2 cells in response to PGD2
released from IgE/anti-IgE treated nasal polyp tissue},
journal = {Allergy},
year = {2010},
volume = {65},
pages = {304--310},
number = {3},
abstract = {To cite this article: Pérez- Novo CA, Holtappels G, Vinall SL, Xue
L, Zhang N, Bachert C, Pettipher R. CRTH2 mediates the activation
of human Th2 cells in response to PGD2 released from IgE/anti-IgE
treated nasal polyp tissue. Allergy 2010; 65: 304–310. Abstract
Background:  Mast cells release mediators upon stimulation that
contribute to the pathogenesis of chronic airway disease, including
the recruitment and activation of Th2 lymphocytes. The objective
was to determine the involvement of prostaglandin D2 (PGD2) and its
receptors in the chemotaxis of Th2 cells, using nasal polyp tissue.Methods: 
Tissue explants from ten patients with nasal polyposis were incubated
with RPMI alone or RPMI containing IgE/anti-IgE for 30Â min. Some
samples were treated with diclofenac to inhibit the production of
PGD2. Supernatants were assayed for PGD2 content and for their ability
to promote human Th2 cell chemotaxis in the presence and absence
of a CRTH2 antagonist. Transcript levels of D protanoid receptor
type 1 (DP1), chemoattractant receptor-homologous receptor expressed
on Th2 cells (CRTH2) and PGD2 synthase were analysed by real time
PCR.Results:  Increased release of PGD2 by nasal polyp tissue treated
with IgE/anti-IgE was significantly inhibited by preincubation of
the tissue with diclofenac. Transcript levels of PGD2 synthase, DP1
and CRTH2 receptors increased after stimulation with IgE/anti-IgE.
Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused
significantly increased chemotaxis of Th2 cells. The levels of PGD2
produced and the degree of Th2 cell chemotaxis were highly correlated.
Diclofenac inhibited the production of Th2 cell chemotactic activity,
and the chemotactic effect of the supernatant on Th2 cells was inhibited
by the CRTH2 antagonist ramatroban.Conclusion:  These data suggest
that in immunologically activated nasal polyp tissue, PGD2 produced
by mast cells promotes the migration of Th2 cells through a CRTH2
dependent mechanism.},
issn = {1398-9995},
keywords = {anti-IgE, chemotaxis, CRTH2, Prostaglandin D2, Th2 cells, upper airways},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1398-9995.2009.02204.x}
}
@ARTICLE{Paelmke2011,
author = {Pälmke, Nina and Santacruz, Diana and Walter, Jörn},
title = {Comprehensive analysis of DNA-methylation in mammalian tissues using
MeDIP-chip},
journal = {Methods},
year = {2011},
volume = {53},
pages = {175--184},
number = {2},
month = feb,
abstract = {Genome-wide mapping of epigenetic changes is essential for understanding
the mechanisms involved in gene regulation during cell differentiation
and embryonic development. DNA-methylation is one of these key epigenetic
marks that is directly linked to gene expression is. Methylated DNA
immunoprecipitation (MeDIP) is a recently devised method used to
determine the distribution of DNA-methylation within functional regions
(e.g., promoters) or in the entire genome robustly and cost-efficiently.
This approach is based on the enrichment of methylated DNA with an
antibody that specifically binds to 5-methyl-cytosine and can be
combined with PCR, microarrays or high-throughput sequencing. This
article outlines the experimental procedure of MeDIP-chip and provides
a comprehensive summary of quality control strategies and primary
data analysis.},
booktitle = {Functional Mouse Genomics},
issn = {1046-2023},
keywords = {DNA-methylation, Methylated DNA immunoprecipitation (MeDIP), Mircoarrays,
Quantitative real time PCR (qPCR), MeDIP-chip quality control, Enrichment
of methylated regions, High-density tiling arrays},
url = {http://www.sciencedirect.com/science/article/pii/S1046202310001878}
}
@ARTICLE{Paerssinen2008,
author = {Pärssinen, Jenita and Alarmo, Emma-Leena and Khan, Sofia and Karhu,
Ritva and Vihinen, Mauno and Kallioniemi, Anne},
title = {Identification of differentially expressed genes after PPM1D silencing
in breast cancer},
journal = {Cancer Letters},
year = {2008},
volume = {259},
pages = {61--70},
number = {1},
month = jan,
abstract = {Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent
1 delta) has been observed in various cancer cell lines and primary
tumors and has also been associated with cancers of poor prognosis.
In addition to the negative feedback regulation of p38-p53 signaling,
PPM1D inhibits other tumor suppressor activities and is involved
in the control of DNA damage and repair pathways. To elucidate the
functional significance of PPM1D in breast cancer, we employed RNA
interference to downregulate PPM1D expression in BT-474, MCF7, and
ZR-75-1 breast cancer cell lines and then investigated the effects
of PPM1D silencing on global gene expression patterns and signaling
pathways using oligonucleotide microarrays. We identified 1798 differentially
expressed (at least a two-fold change) gene elements with functions
related to key cellular processes, such as regulation of cell cycle,
assembly of various intracellular structures and components, and
regulation of signaling pathways and metabolic cascades. For instance,
genes involved in apoptosis (NR4A1, RAB25, PLK1), formation of nucleosome
structure (HIST1H2AC, HIST1H2BF, HIST1H2BO, HIST1H1D), and hormone
related activities (NR4A1, ESR1, STC1) were among the differentially
expressed genes. Overall, our findings suggest that PPM1D contributes
to breast cancer associated phenotypic characteristics by directly
or indirectly affecting several important cellular signaling pathways.},
issn = {0304-3835},
keywords = {PPM1D, Breast cancer, RNA interference, Oligonucleotide microarray,
Gene expression},
url = {http://www.sciencedirect.com/science/article/B6T54-4R1731K-6/2/1601d0abaf6a63cc5b751b576a90b03d}
}
@ARTICLE{PerezNovo2010,
author = {Pérez Novo, C. A. and Jedrzejczak-Czechowicz, M. and Lewandowska-Polak,
A. and Claeys, C. and Holtappels, G. and Van Cauwenberge, P. and
Kowalski, M. L. and Bachert, C.},
title = {T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral
blood mononuclear cells from patients with nasal polyps-asthma after
staphylococcal superantigen stimulation},
journal = {Clinical \& Experimental Allergy},
year = {2010},
volume = {40},
pages = {1323--1332},
number = {9},
abstract = {Cite this as: C. A. Pérez Novo, M. Jedrzejczak-Czechowicz, A. Lewandowska-Polak,
C. Claeys, G. Holtappels, P. Van Cauwenberge, M. L. Kowalski and
C. Bachert, Clinical & Experimental Allergy, 2010 (40) 1323–1332.
Summary Background Staphylococcal superantigens may modulate airway
inflammatory disease.Objective We assessed the effect of Staphylococcus
aureus enterotoxin B (SEB) on T cell activation in patients with
nasal polyps and asthma, and its possible link to aspirin hypersensitivity.Methods
Leucocytes were isolated from five healthy subjects (controls), five
asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced
asthma (NP-AIA). Cells were incubated with increasing concentrations
of SEB for 4 and 18Â h. Release of TH1/TH2 cytokines was assessed
by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed
by qPCR and flow cytometry.Results After 4 and 18Â h, SEB significantly
increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations
in supernatants of both NP polyp groups compared with controls. Baseline
Foxp3 was significantly decreased in both NP-asthma groups. Incubation
with SEB for 4Â h induced a limited up-regulation of Foxp3 in NP-AIA
patients, which was switched off consecutively. Foxp3 was significantly
up-regulated in the control group after 18Â h, but not in the NP-asthmatic
groups. In parallel, TNFRS18-L mRNA significantly increased after
18Â h in the NP-asthma groups compared with control subjects. This
molecule was highly expressed in CD11c+CD14+ cells and its levels
increased after 18 and 24Â h culture in the NP-asthma patients.Conclusion
SEB induces both TH1 and TH2 pro-inflammatory responses in patients
with nasal polyps and asthma regardless of the presence of aspirin
hypersensitivity. The nature of this response may be linked to a
basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or
to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors.},
issn = {1365-2222},
keywords = {aspirin hypersensitivity, Foxp3, nasal polyposis, regulatory T cells,
staphylococcal enterotoxin B, TH1/TH2 cytokines, TNFRS18-L},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2222.2010.03577.x}
}
@ARTICLE{Perez2011,
author = {Pérez, Cristian A. and Stanley, Sarah A. and Wysocki, Robert W. and
Havranova, Jana and Ahrens-Nicklas, Rebecca and Onyimba, Frances
and Friedman, Jeffrey M.},
title = {Molecular Annotation of Integrative Feeding Neural Circuits},
journal = {Cell Metabolism},
year = {2011},
volume = {13},
pages = {222--232},
number = {2},
month = feb,
abstract = {Summary The identity of higher-order neurons and circuits playing
an associative role to control feeding is unknown. We injected pseudorabies
virus, a retrograde tracer, into masseter muscle, salivary gland,
and tongue of BAC-transgenic mice expressing GFP in specific neural
populations and identified several CNS regions that project multisynaptically
to the periphery. MCH and orexin neurons were identified in the lateral
hypothalamus, and Nurr1 and Cnr1 in the amygdala and insular/rhinal
cortices. Cholera toxin [beta] tracing showed that insular Nurr1+
and Cnr1+ neurons project to the amygdala or lateral hypothalamus,
respectively. Finally, we show that cortical Cnr1+ neurons show increased
Cnr1 mRNA and c-Fos expression after fasting, consistent with a possible
role for Cnr1+ neurons in feeding. Overall, these studies define
a general approach for identifying specific molecular markers for
neurons in complex neural circuits. These markers now provide a means
for functional studies of specific neuronal populations in feeding
or other complex behaviors.},
issn = {1550-4131},
url = {http://www.sciencedirect.com/science/article/pii/S1550413110004559}
}
@ARTICLE{Perez2009,
author = {Pérez, Paola and Anaya, Juan-Manuel and Aguilera, Sergio and Urzúa,
Ulises and Munroe, David and Molina, Claudio and Hermoso, Marcela
A. and Cherry, James Michael and Alliende, Cecilia and Olea, Nancy
and Ruiz-Narváez, Edward and González, María-Julieta},
title = {Gene expression and chromosomal location for susceptibility to Sjögren's
syndrome},
journal = {Journal of Autoimmunity},
year = {2009},
volume = {33},
pages = {99--108},
number = {2},
month = sep,
abstract = {Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune
disease affecting mainly the exocrine glands. Its physio-pathology
is poorly understood and most of the knowledge has been related to
the inflammatory component. The aim of this work was to evaluate
gene expression profiling in fractions enriched in epithelial cells
from labial salivary glands (LSGs) of patients with primary SS and
identify chromosomal regions harboring susceptibility genes expressed
in epithelial cells. A combined approach of gene expression and genome-wide
association study was used. Enriched epithelial cell fractions were
obtained from LSGs of patients and controls. Amplified total RNA
was labeled and hybridized to 10K cDNA microarrays. Results were
normalized and subjected to statistical and functional analysis.
A genome-wide microsatellite screen at 10 cM resolution (393 markers)
was performed. In salivary gland-epithelial cells from patients 528
genes were expressed differentially in comparison to controls. Pathways
not previously linked to disease were found to be altered. Twenty-eight
and 15 genes associated with apoptosis were up-regulated and down
regulated, respectively. Interferon-related genes, most of which
participated in interferon signaling, were also found to be up-regulated.
From the genome-wide screen, 6 markers showed evidence of highly
significant association with the disease. Of these, five loci harbor
genes differentially expressed in patients LSG-epithelial cells.
Our results show that in enriched gland-epithelial cells of pSS,
both pro-apoptotic/anti-apoptotic and interferon signaling inhibition/stimulation
balances may occur. Genes found over-expressed in epithelial cells
are candidates for disease susceptibility.},
issn = {0896-8411},
keywords = {Sjögren's syndrome, cDNA microarray, Epithelial cells, Apoptosis,
Interferon, Genome-wide association study},
url = {http://www.sciencedirect.com/science/article/B6WHC-4WH0JSX-1/2/2d88fbcb5fcc6bc31f1dd4f8cf9633a6}
}
@ARTICLE{Perez-Berezo2011,
author = {Pérez-Berezo, Teresa and Franch, Angels and Ramos-Romero, Sara and
Castellote, Cristina and Pérez-Cano, Francisco J. and Castell, Margarida},
title = {Cocoa-enriched diets modulate intestinal and systemic humoral immune
response in young adult rats},
journal = {Molecular Nutrition \& Food Research},
year = {2011},
volume = {55},
pages = {S56--S66},
number = {S1},
abstract = {Scope: Previous studies have shown that a highly enriched cocoa diet
affects both intestinal and systemic immune function in young rats.
The aim of this study was to elucidate whether diets containing lower
amounts of cocoa could also influence the systemic and intestinal
humoral immune response.Methods and results: Fecal and serum samples
were collected during the study and, at the end, intestinal washes
were obtained and mesenteric lymph nodes and small-intestine walls
were excised for gene expression assessment. IgA, IgM, IgG1, IgG2a,
IgG2b and IgG2c concentrations were quantified in serum whereas S-IgA
and S-IgM were determined in feces and intestinal washes. Animals
receiving 5 and 10% cocoa for 3 wk showed no age-related increase
in serum IgG1 and IgG2a concentrations, and IgG2a values were significantly
lower than those in reference animals. Serum IgM was also decreased
by the 10% cocoa diet. The 5 and 10% cocoa diets dramatically reduced
intestinal S-IgA concentration and modified the expression of several
genes involved in IgA synthesis. A diet containing 2% cocoa had no
effect on most of the studied variables.Conclusion: The results demonstrate
the downregulatory effect of a 5% or higher cocoa diet on the systemic
and intestinal humoral immune response in adult rats.},
doi = {10.1002/mnfr.201000588},
issn = {1613-4133},
keywords = {Cocoa, Gut-associated lymphoid tissue, Humoral immune response, Immunoglobulin},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/mnfr.201000588}
}
@ARTICLE{Perez-Enciso2009,
author = {Pérez-Enciso, Miguel and Ferraz, André and Ojeda, Ana and López-Béjar,
Manel},
title = {Impact of breed and sex on porcine endocrine transcriptome: a bayesian
biometrical analysis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {89},
number = {1},
abstract = {BACKGROUND:Transcriptome variability is due to genetic and environmental
causes, much like any other complex phenotype. Ascertaining the transcriptome
differences between individuals is an important step to understand
how selection and genetic drift may affect gene expression. To that
end, extant divergent livestock breeds offer an ideal genetic material.RESULTS:We
have analyzed with microarrays five tissues from the endocrine axis
(hypothalamus, adenohypophysis, thyroid gland, gonads and fat tissue)
of 16 pigs from both sexes pertaining to four extreme breeds (Duroc,
Large White, Iberian and a cross with SinoEuropean hybrid line).
Using a Bayesian linear model approach, we observed that the largest
breed variability corresponded to the male gonads, and was larger
than at the remaining tissues, including ovaries. Measurement of
sex hormones in peripheral blood at slaughter did not detect any
breed-related differences. Not unexpectedly, the gonads were the
tissue with the largest number of sex biased genes. There was a strong
correlation between sex and breed bias expression, although the most
breed biased genes were not the most sex biased genes. A combined
analysis of connectivity and differential expression suggested three
biological processes as being primarily different between breeds:
spermatogenesis, muscle differentiation and several metabolic processes.CONCLUSION:These
results suggest that differences across breeds in gene expression
of the male gonads are larger than in other endocrine tissues in
the pig. Nevertheless, the strong presence of breed biased genes
in the male gonads cannot be explained solely by changes in spermatogenesis
nor by differences in the reproductive tract development.},
doi = {10.1186/1471-2164-10-89},
issn = {1471-2164},
pubmedid = {19239697},
url = {http://www.biomedcentral.com/1471-2164/10/89}
}
@ARTICLE{Peterfi2007,
author = {Péterfi, Zoltán and Kustos, Ildikó and Kilár, Ferenc and Kocsis,
Béla},
title = {Microfluidic chip analysis of outer membrane proteins responsible
for serological cross-reaction between three Gram-negative bacteria:
Proteus morganii O34, Escherichia coli O111 and Salmonella Adelaide
O35},
journal = {Journal of Chromatography A},
year = {2007},
volume = {1155},
pages = {214--217},
number = {2},
month = jul,
abstract = {Bacterial strains have complex and individual antigenic structure,
which provides basis for their serological identification. However,
serological cross-reaction may occur when antibodies against a certain
strain recognize other strains too. The molecular basis of this phenomenon
is the expression of similar or identical antigenic epitopes on the
surface of different bacterial cells. Such cross-reactions might
harden the serological diagnosis of pathogenic bacteria. But it can
be also advantageous, when antigens of non-pathogenic strains can
be used in the serological examinations. Serological cross-reaction
between three taxonomically different strains - Proteus morganii
O34 (8662/64), Escherichia coli O111 and Salmonella Adelaide O35
- have been described. It has been proven that it is based partially
on the similar lipopolysaccharide structures of these pathogens.
In this study the involvement of the outer membrane proteins of these
strains in the serological cross-reaction is presented. Microfluidic
chip technology was applied for the detection of common proteins,
which provided fast and quantitative data about the proteins that
might be responsible for serological cross-reaction. Two outer membrane
proteins with apparent molecular mass of 36 and 41 kDa, respectively,
could be detected in the profile of each strain, while individual
dominating protein peaks have also appeared in the protein profiles.
The presence of common protein antigens was proven by Western blotting.},
booktitle = {15th International Symposium on Capillary Electroseparation Techniques},
issn = {0021-9673},
keywords = {Serological cross-reaction, Microchip electrophoresis, Bacteria, Outer
membrane protein},
url = {http://www.sciencedirect.com/science/article/B6TG8-4N68NJ1-9/2/c504285d8a8ce976d25922476b57a018}
}
@ARTICLE{Qi2011,
author = {Qi, Weiwei and Sun, Fan and Wang, Qianjie and Chen, Mingluan and
Huang, Yunqing and Feng, Yu-Qi and Luo, Xiaojin and Yang, Jinshui},
title = {Rice Ethylene-Response AP2/ERF Factor OsEATB Restricts Internode
Elongation by Down-Regulating a Gibberellin Biosynthetic Gene},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {216-228},
number = {1},
abstract = {Plant height is a decisive factor in plant architecture. Rice (Oryza
sativa) plants have the potential for rapid internodal elongation,
which determines plant height. A large body of physiological research
has shown that ethylene and gibberellin are involved in this process.
The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF)
family of transcriptional factors is only present in the plant kingdom.
This family has various developmental and physiological functions.
A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering
and panicle branching) was cloned from indica rice variety 9311.
Bioinformatic analysis suggested that this ERF has a potential new
function. Ectopic expression of OsEATB showed that the cross talk
between ethylene and gibberellin, which is mediated by OsEATB, might
underlie differences in rice internode elongation. Analyses of gene
expression demonstrated that OsEATB restricts ethylene-induced enhancement
of gibberellin responsiveness during the internode elongation process
by down-regulating the gibberellin biosynthetic gene, ent-kaurene
synthase A. Plant height is negatively correlated with tiller number,
and higher yields are typically obtained from dwarf crops. OsEATB
reduces rice plant height and panicle length at maturity, promoting
the branching potential of both tillers and spikelets. These are
useful traits for breeding high-yielding crops.},
doi = {10.1104/pp.111.179945},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/1/216.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/1/216}
}
@ARTICLE{Qi2012,
author = {Xiao-Hua Qi and Xue-Wen Xu and Xiao-Jian Lin and Wen-Jie Zhang and
Xue-Hao Chen},
title = {Identification of differentially expressed genes in cucumber (Cucumis
sativus L.) root under waterlogging stress by digital gene expression
profile},
journal = {Genomics},
year = {2012},
pages = { - },
number = {0},
abstract = {High-throughput tag-sequencing (Tag-seq) analysis based on the Solexa
Genome Analyzer platform was applied to analyze the gene expression
profiling of cucumber plant at 5 time points over a 24 h period
of waterlogging treatment. Approximately 5.8 million total clean
sequence tags per library were obtained with 143013 distinct clean
tag sequences. Approximately 23.69%–29.61% of the distinct clean
tags were mapped unambiguously to the unigene database, and 53.78%–60.66%
of the distinct clean tags were mapped to the cucumber genome database.
Analysis of the differentially expressed genes revealed that most
of the genes were down-regulated in the waterlogging stages, and
the differentially expressed genes mainly linked to carbon metabolism,
photosynthesis, reactive oxygen species generation/scavenging, and
hormone synthesis/signaling. Finally, quantitative real-time polymerase
chain reaction using nine genes independently verified the tag-mapped
results. This present study reveals the comprehensive mechanisms
of waterlogging-responsive transcription in cucumber.},
doi = {10.1016/j.ygeno.2011.12.008},
issn = {0888-7543},
keywords = {Cucumber},
url = {http://www.sciencedirect.com/science/article/pii/S0888754311002825}
}
@ARTICLE{Qian2010,
author = {Qian, Hong and Xu, Jiasen and Lalioti, Maria D. and Gulle, Kanat
and Sakkas, Denny},
title = {Oocyte Numbers in the Mouse Increase after Treatment with 5-Aminoisoquinolinone:
A Potent Inhibitor of Poly(ADP-ribosyl)ation},
journal = {Biol Reprod},
year = {2010},
volume = {82},
pages = {1000--1007},
number = {5},
month = may,
abstract = {Poly(ADP-ribosyl)ation is a posttranslational protein modification
carried out by a family of enzymes referred to as poly(ADP-ribose)
polymerases (PARPs). It has been proposed that the broad nuclear
distribution of PARPs may allow them to modulate gene expression
in addition to their more accepted role as DNA repair mediators.
The role of poly(ADP-ribosyl)ation during oogenesis and folliculogenesis
is unknown. Here we found that when 3- to 4-wk-old mice were injected
with 5-amninoisoquinolinone, a water soluble inhibitor of poly(ADP-ribosyl)ation,
it leads to considerably increased oocyte numbers and a dramatic
increase in primordial follicle numbers. Furthermore, we show that
inhibition of poly(ADP-ribosyl)ation leads to an increased expression
of specific genes and pathways in mouse ovaries, in particular, transforming
growth factor superfamily members. Our results demonstrate that poly(ADP-ribosyl)ation,
is important in oogenesis and folliculogenesis, and it may have a
differential role in regulating gene expression, DNA repair, and
apoptosis. The novel function of poly(ADP-ribosyl)ation in oogenesis
and folliculogenesis sheds light on the alternative role that DNA
repair mediators may play in cellular development and differentiation.},
url = {http://www.biolreprod.org/cgi/content/abstract/82/5/1000}
}
@ARTICLE{Qian2005,
author = {Qian, Jiaying and Niu, Jiangong and Li, Ming and Chiao, Paul J. and
Tsao, Ming-Sound},
title = {In vitro Modeling of Human Pancreatic Duct Epithelial Cell Transformation
Defines Gene Expression Changes Induced by K-ras Oncogenic Activation
in Pancreatic Carcinogenesis},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {5045--5053},
number = {12},
month = jun,
abstract = {Genetic analysis of pancreatic ductal adenocarcinomas and their putative
precursor lesions, pancreatic intraepithelial neoplasias (PanIN),
has shown a multistep molecular paradigm for duct cell carcinogenesis.
Mutational activation or inactivation of the K-ras, p16INK4A, Smad4,
and p53 genes occur at progressive and high frequencies in these
lesions. Oncogenic activation of the K-ras gene occurs in >90% of
pancreatic ductal carcinoma and is found early in the PanIN-carcinoma
sequence, but its functional roles remain poorly understood. We show
here that the expression of K-rasG12V oncogene in a near diploid
HPV16-E6E7 gene immortalized human pancreatic duct epithelial cell
line originally derived from normal pancreas induced the formation
of carcinoma in 50% of severe combined immunodeficient mice implanted
with these cells. A tumor cell line established from one of these
tumors formed ductal cancer when implanted orthotopically. These
cells also showed increased activation of the mitogen-activated protein
kinase, AKT, and nuclear factor-{kappa}B pathways. Microarray expression
profiling studies identified 584 genes whose expression seemed specifically
up-regulated by the K-ras oncogene expression. Forty-two of these
genes have been reported previously as differentially overexpressed
in pancreatic cancer cell lines or primary tumors. Real-time PCR
confirmed the overexpression of a large number of these genes. Immunohistochemistry
done on tissue microarrays constructed from PanIN and pancreatic
cancer samples showed laminin {beta}3 overexpression starting in
high-grade PanINs and occurring in >90% of pancreatic ductal carcinoma.
The in vitro modeling of human pancreatic duct epithelial cell transformation
may provide mechanistic insights on gene expression changes that
occur during multistage pancreatic duct cell carcinogenesis.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/12/5045}
}
@ARTICLE{Qiang2011,
author = {Liang Qiang and Ryousuke Fujita and Toru Yamashita and Sergio Angulo
and Herve Rhinn and David Rhee and Claudia Doege and Lily Chau and
Laetitia Aubry and William B. Vanti and Herman Moreno and Asa Abeliovich},
title = {Directed Conversion of Alzheimer's Disease Patient Skin Fibroblasts
into Functional Neurons},
journal = {Cell},
year = {2011},
volume = {146},
pages = {359 - 371},
number = {3},
abstract = {Summary Directed conversion of mature human cells, as from fibroblasts
to neurons, is of potential clinical utility for neurological disease
modeling as well as cell therapeutics. Here, we describe the efficient
generation of human-induced neuronal (hiN) cells from adult skin
fibroblasts of unaffected individuals and Alzheimer's patients, using
virally transduced transcription regulators and extrinsic support
factors. hiN cells from unaffected individuals display morphological,
electrophysiological, and gene expression profiles that typify glutamatergic
forebrain neurons and are competent to integrate functionally into
the rodent CNS. hiN cells from familial Alzheimer disease (FAD) patients
with presenilin-1 or -2 mutations exhibit altered processing and
localization of amyloid precursor protein (APP) and increased production
of Aβ, relative to the source patient fibroblasts or hiN cells from
unaffected individuals. Together, our findings demonstrate directed
conversion of human fibroblasts to a neuronal phenotype and reveal
cell type-selective pathology in hiN cells derived from FAD patients.},
doi = {10.1016/j.cell.2011.07.007},
issn = {0092-8674},
url = {http://www.sciencedirect.com/science/article/pii/S0092867411007641}
}
@ARTICLE{Qiao2008,
author = {Qiao, Renli and Yan, Weihong and Clavijo, Carlos and Mehrian-Shai,
Ruty and Zhong, Qian and Kim, Kwang-Jin and Ann, David and Crandall,
Edward D. and Borok, Zea},
title = {Effects of KGF on Alveolar Epithelial Cell Transdifferentiation Are
Mediated by JNK Signaling},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2008},
volume = {38},
pages = {239--246},
number = {2},
month = feb,
abstract = {Rat alveolar epithelial cells (AEC) in primary culture transdifferentiate
from a type II (AT2) toward a type I (AT1) cell-like phenotype, a
process that can be both prevented and reversed by keratinocyte growth
factor (KGF). Microarray analysis revealed that these effects of
KGF are associated with up-regulation of key molecules in the mitogen-activated
protein kinase (MAPK) pathway. To further explore the role of three
key MAPK (i.e., extracellular signal-related kinase [ERK] 1/2, c-Jun
N-terminal kinase [JNK] and p38) in mediating effects of KGF on AEC
phenotype, primary rat AEC cultivated in minimal defined serum-free
medium (MDSF) were treated with KGF (10 ng/ml) from Day 4 for intervals
up to 48 hours. Exposure to KGF activated all three MAPK, JNK, ERK1/2,
and p38. Inhibition of JNK, but not of ERK1/2 or p38, abrogated the
ability of KGF to maintain the AT2 cell phenotype, as evidenced by
loss of expression of lamellar membrane protein (p180) and increased
reactivity with the AT1 cell-specific monoclonal antibody VIIIB2
by Day 6 in culture. Overexpression of JNKK2, upstream kinase of
JNK, increased activation of endogenous c-Jun in association with
increased expression of p180 and abrogation of AQP5, suggesting that
activation of c-Jun promotes retention of the AT2 cell phenotype.
These results indicate that retention of the AT2 cell phenotype by
KGF involves c-Jun and suggest that activation of c-Jun kinase may
be an important determinant of maintenance of AT2 cell phenotype.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/38/2/239}
}
@ARTICLE{Qin2010,
author = {Qin, Bolin and Polansky, Marilyn M. and Harry, Dawson and Anderson,
Richard A.},
title = {Green tea polyphenols improve cardiac muscle mRNA and protein levels
of signal pathways related to insulin and lipid metabolism and inflammation
in insulin-resistant rats},
journal = {Mol. Nutr. Food Res.},
year = {2010},
volume = {54},
pages = {S14--S23},
number = {S1},
abstract = {Abstract 10.1002/mnfr.200900306.abs Epidemiological studies indicate
that the consumption of green tea polyphenols (GTP) may reduce the
risk of coronary artery disease. To explore the underlying mechanisms
of action at the molecular level, we examined the effects of GTP
on the cardiac mRNA and protein levels of genes involved in insulin
and lipid metabolism and inflammation. In rats fed a high-fructose
diet, supplementation with GTP (200 mg/kg BW daily dissolved in
distilled water) for 6 wk, reduced systemic blood glucose, plasma
insulin, retinol-binding protein 4, soluble CD36, cholesterol, triglycerides,
free fatty acids and LDL-C levels, as well as the pro-inflammatory
cytokines, tumor necrosis factor-α (TNF-α) and IL-6. GTP did not
affect food intake, bodyweight and heart weight. In the myocardium,
GTP also increased the insulin receptor (Ir), insulin receptor substrate
1 and 2 (Irs1 and Irs2), phosphoinositide-3-kinase (Pi3k), v-akt
murine thymoma viral oncogene homolog 1 (Akt1), glucose transporter
1 and 4 (Glut1 and Glut4) and glycogen synthase 1 (Gys1) expression
but inhibited phosphatase and tensin homolog deleted on chromosome
ten (Pten) expression and decreased glycogen synthase kinase 3β
(Gsk3β) mRNA expression. The sterol regulatory element-binding protein-1c
(Srebp1c) mRNA, microsomal triglyceride transfer protein (Mttp) mRNA
and protein, Cd36 mRNA and cluster of differentiation 36 protein
levels were decreased and peroxisome proliferator-activated receptor
(Ppar)γ mRNA levels were increased. GTP also decreased the inflammatory
factors: Tnf, Il1b and Il6 mRNA levels, and enhanced the anti-inflammatory
protein, zinc-finger protein, protein and mRNA expression. In summary,
consumption of GTP ameliorated the detrimental effects of high-fructose
diet on insulin signaling, lipid metabolism and inflammation in the
cardiac muscle of rats.},
issn = {1613-4133},
keywords = {Cardiac insulin, Green tea polyphenols, Lipid and inflammatory signaling},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/mnfr.200900306}
}
@ARTICLE{Qin2009,
author = {Qin, Bolin and Polansky, Marilyn M. and Sato, Yuzo and Adeli, Khosrow
and Anderson, Richard A.},
title = {Cinnamon extract inhibits the postprandial overproduction of apolipoprotein
B48-containing lipoproteins in fructose-fed animals},
journal = {The Journal of Nutritional Biochemistry},
year = {2009},
volume = {20},
pages = {901--908},
number = {11},
month = nov,
abstract = {We have reported previously that a cinnamon extract (CE), high in
type A polyphenols, prevents fructose feeding-induced decreases in
insulin sensitivity and suggested that improvements of insulin sensitivity
by CE were attributable, in part, to enhanced insulin signaling.
In this study, we examined the effects of CE on postprandial apolipoprotein
(apo) B-48 increase in fructose-fed rats, and the secretion of apoB48
in freshly isolated intestinal enterocytes of fructose-fed hamsters.
In an olive oil loading study, a water-soluble CE (Cinnulin PF, 50
mg/kg body weight, orally) decreased serum triglyceride (TG) levels
and the over production of total- and TG-rich lipoprotein-apoB48.
In ex vivo 35S labeling study, significant decreases were also observed
in apoB48 secretion into the media in enterocytes isolated from fructose-fed
hamsters. We also investigated the molecular mechanisms of the effects
of CE on the expression of genes of the insulin signaling pathway
[insulin receptor (IR), IR substrate (IRS)1, IRS2 and Akt1], and
lipoprotein metabolism [microsomal TG transfer protein (MTP), sterol
regulatory element-binding protein (SREBP1c) in isolated primary
enterocytes of fructose-fed hamsters, using quantitative real-time
polymerase chain reaction. The CE reversed the expression of the
impaired IR, IRS1, IRS2 and Akt1 mRNA levels and inhibited the overexpression
of MTP and SREBP1c mRNA levels of enterocytes. Taken together, our
data suggest that the postprandial hypertriglycerides and the overproduction
of apoB48 can be acutely inhibited by a CE by a mechanism involving
improvements of insulin sensitivity of intestinal enterocytes and
regulation of MTP and SREBP1c levels. We present both in vivo and
ex vivo evidence that a CE improves the postprandial overproduction
of intestinal apoB48-containing lipoproteins by ameliorating intestinal
insulin resistance and may be beneficial in the control of lipid
metabolism.},
issn = {0955-2863},
keywords = {Cinnamon Extract, Postprandial apob-48, Intestinal Insulin Signaling},
url = {http://www.sciencedirect.com/science/article/B6T8P-4TVR26P-8/2/b01de0f3d85199f967f06081bf9f060d}
}
@ARTICLE{Qin2008,
author = {Qin, Jian and Jones, Robert C. and Ramakrishnan, Ramesh},
title = {Studying copy number variations using a nanofluidic platform},
journal = {Nucleic Acids Res.},
year = {2008},
volume = {36},
pages = {e116--},
number = {18},
month = oct,
abstract = {Copy number variations (CNVs) in the human genome are conventionally
detected using high-throughput scanning technologies, such as comparative
genomic hybridization and high-density single nucleotide polymorphism
(SNP) microarrays, or relatively low-throughput techniques, such
as quantitative polymerase chain reaction (PCR). All these approaches
are limited in resolution and can at best distinguish a twofold (or
50%) difference in copy number. We have developed a new technology
to study copy numbers using a platform known as the digital array,
a nanofluidic biochip capable of accurately quantitating genes of
interest in DNA samples. We have evaluated the digital array's performance
using a model system, to show that this technology is exquisitely
sensitive, capable of differentiating as little as a 15% difference
in gene copy number (or between 6 and 7 copies of a target gene).
We have also analyzed commercial DNA samples for their CYP2D6 copy
numbers and confirmed that our results were consistent with those
obtained independently using conventional techniques. In a screening
experiment with breast cancer and normal DNA samples, the ERBB2 gene
was found to be amplified in about 35% of breast cancer samples.
The use of the digital array enables accurate measurement of gene
copy numbers and is of significant value in CNV studies.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/36/18/e116}
}
@ARTICLE{Qin2010b,
author = {Qin, Limei and Chen, Yaosheng and Niu, Yuna and Chen, Weiquan and
Wang, Qiwei and Xiao, Shuqi and Li, Anning and Xie, Ying and Li,
Jing and Zhao, Xiao and He, Zuyong and Mo, Delin},
title = {A deep investigation into the adipogenesis mechanism: Profile of
microRNAs regulating adipogenesis by modulating the canonical Wnt/ß-catenin
signaling pathway},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {320},
number = {1},
abstract = {BACKGROUND:MicroRNAs (miRNAs) are a large class of tiny non-coding
RNAs (~22-24 nt) that regulate diverse biological processes at the
posttranscriptional level by controlling mRNA stability or translation.
As a molecular switch, the canonical Wnt/ß-catenin signaling pathway
should be suppressed during the adipogenesis; However, activation
of this pathway leads to the inhibition of lipid depots formation.
The aim of our studies was to identify miRNAs that might be involved
in adipogenesis by modulating WNT signaling pathway. Here we established
two types of cell model, activation and repression of WNT signaling,
and investigated the expression profile of microRNAs using microarray
assay.RESULTS:The high throughput microarray data revealed 18 miRNAs
that might promote adipogenesis by repressing WNT signaling: miR-210,
miR-148a, miR-194, miR-322 etc. Meanwhile, we also identified 29
miRNAs that might have negative effect on adipogenesis by activating
WNT signaling: miR-344, miR-27 and miR-181 etc. The targets of these
miRNAs were also analysed by bioinformatics. To validate the predicted
targets and the potential functions of these identified miRNAs, the
mimics of miR-210 were transfected into 3T3-L1 cells and enlarged
cells with distinct lipid droplets were observed; Meanwhile, transfection
with the inhibitor of miR-210 could markedly decrease differentiation-specific
factors at the transcription level, which suggested the specific
role of miR-210 in promoting adipogenesis. Tcf7l2, the predicted
target of miR-210, is a transcription factor triggering the downstream
responsive genes of WNT signaling, was blocked at transcription level.
Furthermore, the activity of luciferase reporter bearing Tcf7l2 mRNA
3' UTR was decreased after co-transfection with miR-210 in HEK-293FT
cells. Last but not least, the protein expression level of ß-catenin
was increased in the lithium (LiCl) treated 3T3-L1 cells after transfection
with miR-210. These findings suggested that miR-210 could promote
adipogenesis by repressing WNT signaling through targeting Tcf7l2.CONCLUSIONS:The
results suggest the presence of miRNAs in two cell models, providing
insights into WNT pathway-specific miRNAs that can be further characterized
for their potential roles in adipogenesis. To our knowledge, present
study represents the first attempt to unveil the profile of miRNAs
involed in adipogenesis by modulating WNT signaling pathway, which
contributed to deeper investigation of the mechanism of adipogenesis.},
doi = {10.1186/1471-2164-11-320},
issn = {1471-2164},
pubmedid = {20492721},
url = {http://www.biomedcentral.com/1471-2164/11/320}
}
@ARTICLE{QIN2009,
author = {QIN, Li-hua and WANG, Ruo-guang and LI, Sheng and LI, Chun-mei},
title = {Differentially Gene Expression Profile Related to Inflammation in
Endometrial Cells Induce by Lipopolysaccharide},
journal = {Journal of Reproduction and Contraception},
year = {2009},
volume = {20},
pages = {27--34},
number = {1},
month = mar,
abstract = {Objective To investigate differentially expressed genes related to
inflammation in endometrial cells induced by Lipopolysaccharide(LPS).Methods
Normal endometrium in the proliferative phase of specimen from 3
cases for the experiment was collected. The LPS group were treated
with 50 µg/ml LPS. Total RNA was extracted using Trizol reagent from
cells. RNA quality was assessed by determining the OD260/280 ratio
by agarose gel electrophoresis, the chip was scanned by laser scanner.
The acquired was analyzed.Results A total of differentially expressed
genes were found, these genes were relative to many aspects. Among
them, the expression of genes involved in inflammation were up-regulated
by LPS, such as overexpression of IL-1[beta], 8, etc.Conclusion The
results indicates that inflammation-related genes may be one of the
mechanisms of abnormal uterine bleeding by LPS-induced.},
issn = {1001-7844},
keywords = {gene expression profile, lipopolysaccharide(LPS), endometrial cell,
inflammation},
url = {http://www.sciencedirect.com/science/article/B8JBS-4W0WFVX-4/2/718d89ba7e377f0a5c0f5450c1c944b9}
}
@ARTICLE{Qin2011e,
author = {Qin, Mei and Entezam, Ali and Usdin, Karen and Huang, Tianjian and
Liu, Zhong-Hua and Hoffman, Gloria E. and Smith, Carolyn B.},
title = {A mouse model of the fragile X premutation: Effects on behavior,
dendrite morphology, and regional rates of cerebral protein synthesis},
journal = {Neurobiology of Disease},
year = {2011},
volume = {42},
pages = {85--98},
number = {1},
month = apr,
abstract = {Carriers of FMR1 premutation alleles have 55-200 CGG repeats in the
5' untranslated region of the gene. These individuals are at risk
for fragile X associated primary ovarian insufficiency (females)
and, in late life, fragile X associated tremor and ataxia syndrome
(males, and to a lesser extent, females). Premutation carrier status
can also be associated with autism spectrum disorder, attention deficit
hyperactivity disorder, and some cognitive deficits. In premutation
carriers, FMR1 mRNA levels are often higher than those with normal
sized alleles. In contrast, in subjects with full mutation alleles,
(> 200 repeats) the FMR1 gene is silenced and FMR1 mRNA and its product,
FMRP, are absent. We have studied a male knock-in (KI) mouse model
of the fragile X premutation (120-140 repeats) during young adulthood.
In comparison to wild type, KI mice were hyperactive, exhibited less
anxiety in both the open field and the elevated zero maze, were impaired
on the passive avoidance test, and showed some subtle deficits on
a test of social interaction. Motor learning as assessed by the rotarod
test was normal. Dendritic arbors were less complex and spine densities
and lengths increased in medial prefrontal cortex, basal lateral
amygdala, and hippocampus compared with wild type. Regional rates
of cerebral protein synthesis measured in vivo in KI mice were increased.
KI mice also had elevated levels of Fmr1 mRNA and decreased levels
of FMRP. Our results highlight similarities in phenotype between
KI and Fmr1 knockout mice and suggest that the decreased concentration
of FMRP contributes to the phenotype in young adult KI mice.},
issn = {0969-9961},
keywords = {Fragile X syndrome, Fragile X premutation, FMRP, Fmr1, Hyperactivity,
Anxiety, Dendritic spine morphology, Protein synthesis, Social interaction},
url = {http://www.sciencedirect.com/science/article/pii/S096999611100009X}
}
@ARTICLE{Qin2007,
author = {Qin, Nan and Callahan, Sean M. and Dunlap, Paul V. and Stevens, Ann
M.},
title = {Analysis of LuxR Regulon Gene Expression during Quorum Sensing in
Vibrio fischeri},
journal = {J. Bacteriol.},
year = {2007},
volume = {189},
pages = {4127--4134},
number = {11},
month = jun,
abstract = {The regulation of the lux operon (luxICDABEG) of Vibrio fischeri has
been intensively studied as a model for quorum sensing in proteobacteria.
Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis
analysis previously identified several non-Lux proteins in V. fischeri
MJ-100 whose expression was dependent on LuxR and 3-oxo-hexanoyl-L-homoserine
lactone (3-oxo-C6-HSL). To determine if the LuxR-dependent regulation
of the genes encoding these proteins was due to direct transcriptional
control by LuxR and 3-oxo-C6-HSL or instead was due to indirect control
via an unidentified regulatory element, promoters of interest were
cloned into a lacZ reporter and tested for their LuxR and 3-oxo-C6-HSL
dependence in recombinant Escherichia coli. The promoters for qsrP,
acfA, and ribB were found to be directly activated via LuxR-3-oxo-C6-HSL.
The sites of transcription initiation were established via primer
extension analysis. Based on this information and the position of
the lux box-binding site near position -40, all three promoters appear
to have a class II-type promoter structure. In order to more fully
characterize the LuxR regulon in V. fischeri MJ-100, real-time reverse
transcription-PCR was used to study the temporal expression of qsrP,
acfA, and ribB during the exponential and stationary phases of growth,
and electrophoretic mobility shift assays were used to compare the
binding affinities of LuxR to the promoters under investigation.
Taken together, the results demonstrate that regulation of the production
of QsrP, RibB, and AcfA is controlled directly by LuxR at the level
of transcription, thereby establishing that there is a LuxR regulon
in V. fischeri MJ-100 whose genes are coordinately expressed during
mid-exponential growth.},
url = {http://jb.asm.org/cgi/content/abstract/189/11/4127}
}
@ARTICLE{Qin2008a,
author = {Qin, Qiong and Patil, Kiran A. and Gronert, Karsten and Sharma, Sansar
C.},
title = {Neuroprotectin D1 inhibits retinal ganglion cell death following
axotomy},
journal = {Prostaglandins, Leukotrienes and Essential Fatty Acids},
year = {2008},
volume = {79},
pages = {201--207},
number = {6},
month = dec,
abstract = {Neuroprotectin D1 (NPD1), a docosahexaenoic acid-derived autacoid,
is an endogenous neuroprotective and anti-inflammatory mediator that
is generated in the retina and brain. The effects of exogenous NPD1
on retinal ganglion cell (RGC) apoptosis and the role of 12/15-lipoxygenase
(Alox15) in retina were evaluated after optic nerve transection (ONT).
Treatment with NPD1 was associated with significant protection against
RGC death. The percentage of RGC survival in NPD1-treated group was
30% at 2 weeks after ONT as compared with 12% of RGC survival in
the ONT group without treatment. Endogenous NPD1 was a predominant
lipid autocoid in uninjured and axotomized retinas. Alox15 mRNA expression
was upregulated in retinas following ONT suggesting that amplification
of 12/15-lipoxygenase (12/15-LOX) may represent a neuroprotective
response in the rat retina. The density of RGCs was higher in the
normal retina of 12/15-LOX-deficient mice as compared with congenic
controls. Hence, the resident NPD1 has a potential role in the physiological
and pathophysiological responses of the retina.},
issn = {0952-3278},
keywords = {Retinal ganglion cell, Docosahexaenoic acid, 12/15-Lipoxygenase},
url = {http://www.sciencedirect.com/science/article/B6WPH-4TY8W5T-1/2/2303661c7aa5fe79dcfda9fc9069d6df}
}
@ARTICLE{Qin2011d,
author = {Suofu Qin and Ming Ni and Xiuyun Wang and Florence Maurier-Mahé
and Dixie-Lee Shurland and Gerard A. Rodrigues},
title = {Inhibition of RPE cell sterile inflammatory responses and endotoxin-induced
uveitis by a cell-impermeable HSP90 inhibitor},
journal = {Experimental Eye Research},
year = {2011},
volume = {93},
pages = {889 - 897},
number = {6},
abstract = {Dying cells release pro-inflammatory molecules, functioning as cytokines
to trigger cell/tissue inflammation that is relevant to disease pathology.
Heat-shock protein 90 (HSP90) is believed to act as a danger signal
for tissue damage once released extracellularly. Potential roles
of HSP90 were explored in retinal pigment epithelial (RPE) inflammatory
responses to necrosis. Cellular extracts can trigger ARPE-19 cell
inflammatory responses, producing cytokines that lead to an increase
in ARPE-19 cell monolayer permeability. Addition of recombinant HSP90β
mimics the induction of chemokines IL-8 and MCP-1 in cultured RPE
cells, suggesting that released HSP90 can incite RPE cell sterile
inflammatory responses. Consistent with this, classical HSP90 inhibitors
were shown to substantially reduce necrosis-induced cytokine production
and permeability increases in ARPE-19 cells. Moreover, a cell-impermeable
inhibitor, 17-N,N-dimethylaminoethylamino-17-demethoxy-geldanamycin-N-oxide,
also efficiently inhibited necrosis-induced cytokine production and
TNF-α/IL-1β-induced increase in ARPE-19 cell permeability in vitro
and endotoxin-induced development of uveitis in vivo, suggesting
that HSP90 can contribute to necrosis-induced RPE inflammatory responses.
Collectively, our data identify HSP90 as a pro-inflammatory molecule
in RPE cell sterile inflammatory responses.},
doi = {10.1016/j.exer.2011.10.002},
issn = {0014-4835},
keywords = {HSP90},
url = {http://www.sciencedirect.com/science/article/pii/S0014483511002880}
}
@ARTICLE{Qin2007a,
author = {Qin, Taichun and Youssef, Emile M. and Jelinek, Jaroslav and Chen,
Rong and Yang, Allen S. and Garcia-Manero, Guillermo and Issa, Jean-Pierre
J.},
title = {Effect of Cytarabine and Decitabine in Combination in Human Leukemic
Cell Lines},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {4225--4232},
number = {14},
month = jul,
abstract = {Purpose: 1-{beta}-D-Arabinofuranosylcytosine (cytarabine; ara-C) is
the most active agent in myeloid leukemia. 5-Aza-2'-deoxycytidine
(DAC) is a cytosine analogue that inhibits DNA methylation and also
has activity in myeloid leukemia. Therefore, we investigated combining
these two drugs in human leukemia cell lines in vitro. Experimental
Design: We initially examined the effects of ara-C and DAC on human
leukemia cell lines HL60, ML-1, RAji, and Jurkat. We measured IC50
of DAC and ara-C in these cell lines and calculated a combination
index of these two drugs given either simultaneously or sequentially.
In searching for mechanisms relative to epigenetic regulation for
this effect, we examined DNA methylation of LINE and Alu repetitive
elements as a surrogate for global genomic DNA methylation. In addition,
we sorted Annexin V positive and negative cells and measured differences
in LINE methylation between them. Results: The combination of DAC
and ara-C showed additive induction of cell death in ML-1 and synergistic
induction in HL60, Raji, and Jurkat. Sequentially, DAC followed by
ara-C was a synergistic combination in all cell lines. Low-dose DAC
induced more hypomethylation than high doses of the drug, whereas
ara-C had no effects on methylation. The combination of ara-C with
DAC either together or DAC followed by ara-C resulted in inhibition
of LINE demethylation in HL60. The RIL gene, which is silenced by
DNA hypermethylation, was activated by DAC, but the addition of ara-C
to DAC reduced RIL gene activation. DAC treatment increased H3 Lys9
acetylation of Alu elements, whereas ara-C had no effect, and the
addition of ara-C to DAC inhibited this effect. Finally, we showed
that after DAC exposure, Annexin V positive cells were more hypomethylated
than Annexin V negative cells. Conclusion: The combination of DAC
and ara-C showed additive or synergistic effects on cell death in
four human leukemia cell lines in vitro, but antagonism in terms
of epigenetic effects. One possible explanation for these paradoxical
observations is that hypomethylated cells are sensitized to cell
killing by ara-C. These data suggest that DAC used in combination
with ara-C has clinical potential in the treatment of acute myeloid
leukemia.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/14/4225}
}
@ARTICLE{Qin2010a,
author = {Qin, Weiping and Pan, Jiangping and Bauman, William and Cardozo,
Christopher},
title = {Differential alterations in gene expression profiles contribute to
time-dependent effects of nandrolone to prevent denervation atrophy
},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {596},
number = {1},
abstract = {BACKGROUND:Anabolic steroids, such as nandrolone, slow muscle atrophy,
but the mechanisms responsible for this effect are largely unknown.
Their effects on muscle size and gene expression depend upon time,
and the cause of muscle atrophy. Administration of nandrolone for
7 days beginning either concomitantly with sciatic nerve transection
(7 days) or 29 days later (35 days) attenuated denervation atrophy
at 35 but not 7 days. We reasoned that this model could be used to
identify genes that are regulated by nandrolone and slow denervation
atrophy, as well as genes that might explain the time-dependence
of nandrolone effects on such atrophy. Affymetrix microarrays were
used to profile gene expression changes due to nandrolone at 7 and
35 days and to identify major gene expression changes in denervated
muscle between 7 and 35 days. RESULTS:Nandrolone selectively altered
expression of 124 genes at 7 days and 122 genes at 35 days, with
only 20 genes being regulated at both time points. Marked differences
in biological function of genes regulated by nandrolone at 7 and
35 days were observed. At 35, but not 7 days, nandrolone reduced
mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and
the calcineurin inhibitor RCAN2 and increased those for ApoD. At
35 days, correlations between mRNA levels and the size of denervated
muscle were negative for RCAN2, and positive for ApoD. Nandrolone
also regulated genes for Wnt signaling molecules. Comparison of gene
expression at 7 and 35 days after denervation revealed marked alterations
in the expression of 9 transcriptional coregulators, including Ankrd1
and 2, and many transcription factors and kinases. CONCLUSIONS:Genes
regulated in denervated muscle after 7 days administration of nandrolone
are almost entirely different at 7 versus 35 days. Alterations in
levels of FOXO1, and of genes involved in signaling through calcineurin,
mTOR and Wnt may be linked to the favorable action of nandrolone
on denervated muscle. Marked changes in the expression of genes regulating
transcription and intracellular signaling may contribute to the time-dependent
effects of nandrolone on gene expression. },
doi = {10.1186/1471-2164-11-596},
issn = {1471-2164},
pubmedid = {20969782},
url = {http://www.biomedcentral.com/1471-2164/11/596}
}
@ARTICLE{Qin2011b,
author = {Xian-Yang Qin and Feifei Wei and Jun Yoshinaga and Junzo Yonemoto
and Masaru Tanokura and Hideko Sone},
title = {siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator
2 affects hypoxia-inducible factor-1 regulatory signaling and metabolism
in human breast cancer cells},
journal = {FEBS Letters},
year = {2011},
volume = {585},
pages = {3310 - 3315},
number = {20},
abstract = {Recent human studies found that the mRNA expression level of aryl-hydrocarbon
receptor nuclear translocator 2 (ARNT2) was positively associated
with the prognosis of breast cancer. In this study, we used small
interfering RNA techniques to knockdown ARNT2 expression in MCF7
human breast cancer cells, and found that an almost 40% downregulation
of ARNT2 mRNA expression increased the expression of sensitive to
apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau
(0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite
analysis revealed the contents of glucose, glycine, betaine, phosphocholine,
pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent
glycolytic pathway were significantly lower in cells treated with
siARNT2. Our results suggested that ARNT2 might play an important
role in the modulation of HIF-1-regulated signaling and metabolism.},
doi = {10.1016/j.febslet.2011.09.017},
issn = {0014-5793},
keywords = {Aryl-hydrocarbon receptor nuclear translocator 2},
url = {http://www.sciencedirect.com/science/article/pii/S001457931100696X}
}
@ARTICLE{Qin2011,
author = {Xian-Yang Qin and Hiroko Zaha and Reiko Nagano and Jun Yoshinaga
and Junzo Yonemoto and Hideko Sone},
title = {Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator
2 mRNA expression in human breast cancer cells via an estrogen receptor
alpha-dependent mechanism},
journal = {Toxicology Letters},
year = {2011},
volume = {206},
pages = {152 - 157},
number = {2},
abstract = {Environmental chemicals with estrogenic activity, known as xenoestrogens,
may cause impaired reproductive development and endocrine-related
cancers in humans by disrupting endocrine functions. Aryl-hydrocarbon
receptor nuclear translocator 2 (ARNT2) is believed to play important
roles in a variety of physiological processes, including estrogen
signaling pathways, that may be involved in the pathogenesis and
therapeutic responses of endocrine-related cancers. However, much
of the underlying mechanism remains unknown. In this study, we investigated
whether ARNT2 expression is regulated by a range of representative
xenoestrogens in human cancer cell lines. Bisphenol A (BPA), benzyl
butyl phthalate (BBP), and 1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane
(o,p′-DDT) were found to be estrogenic toward BG1Luc4E2 cells by
an E-CALUX bioassay. ARNT2 expression was downregulated by BPA, BBP,
and o,p′-DDT in a dose-dependent manner in estrogen receptor 1
(ESR1)-positive MCF-7 and BG1Luc4E2 cells, but not in estrogen receptor-negative
LNCaP cells. The reduction in ARNT2 expression in cells treated with
the xenoestrogens was fully recovered by the addition of a specific
ESR1 antagonist, MPP. In conclusion, we have shown for the first
time that ARNT2 expression is modulated by xenoestrogens by an ESR1-dependent
mechanism in MCF-7 breast cancer cells.},
doi = {10.1016/j.toxlet.2011.07.007},
issn = {0378-4274},
keywords = {ARNT2},
url = {http://www.sciencedirect.com/science/article/pii/S0378427411014202}
}
@ARTICLE{Qin2011c,
author = {Qin, Y. and Verdegaal, E. M. E. and Siderius, M. and Bebelman, J.
P. and Smit, M. J. and Leurs, R. and Willemze, R. and Tensen, C.
P. and Osanto, S.},
title = {Quantitative expression profiling of G-protein-coupled receptors
(GPCRs) in metastatic melanoma: the constitutively active orphan
GPCR GPR18 as novel drug target},
journal = {Pigment Cell \& Melanoma Research},
year = {2011},
volume = {24},
pages = {207--218},
number = {1},
abstract = {Summary G-protein-coupled receptors (GPCRs) have been implicated in
the tumorigenesis and metastasis of human cancers and are considered
amongst the most desirable targets for drug development. Utilizing
a robust quantitative PCR array, we quantified expression of 94 human
GPCRs, including 75 orphan GPCRs and 19 chemokine receptors, and
36 chemokine ligands, in 40 melanoma metastases from different individuals
and benign nevi. Inter-metastatic site comparison revealed that orphan
GPR174 and CCL28 are statistically significantly overexpressed in
subcutaneous metastases, while P2RY5 is overexpressed in brain metastases.
Comparison between metastases (all three metastatic sites) and benign
nevi revealed that 16 genes, including six orphan receptors (GPR18,
GPR34, GPR119, GPR160, GPR183 and P2RY10) and chemokine receptors
CCR5, CXCR4, and CXCR6, were statistically significantly differentially
expressed. Subsequent functional experiments in yeast and melanoma
cells indicate that GPR18, the most abundantly overexpressed orphan
GPCR in all melanoma metastases, is constitutively active and inhibits
apoptosis, indicating an important role for GPR18 in tumor cell survival.
GPR18 and five other orphan GPCRs with yet unknown biological function
may be considered potential novel anticancer targets in metastatic
melanoma.},
doi = {10.1111/j.1755-148X.2010.00781.x},
issn = {1755-148X},
keywords = {orphan receptors, G-protein-coupled receptors, melanoma, neoplasm,
metastases, drug targeting, gene expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-148X.2010.00781.x}
}
@ARTICLE{Qin2011a,
author = {Yun-Fei Qin and Hui-Min Fang and Qing-Nan Tian and Zhen-Xia Bao and
Ping Lu and Jin-Mei Zhao and Jia Mai and Zhao-Yu Zhu and Lin-Lin
Shu and Li Zhao and San-Jun Chen and Feng Liang and Yi-Zhe Zhang
and Shou-Tao Zhang},
title = {Transcriptome profiling and digital gene expression by deep-sequencing
in normal/regenerative tissues of planarian Dugesia japonica},
journal = {Genomics},
year = {2011},
volume = {97},
pages = {364 - 371},
number = {6},
abstract = {Planarians exhibit an extraordinary ability to regenerate lost body
parts which is attributed to an abundance of pluripotent somatic
stem cells called neoblasts. In this article, we report a transcriptome
sequence of a Planaria subspecies Dugesia japonica derived by high-throughput
sequencing. In addition, we researched transcriptome changes during
different periods of regeneration by using a tag-based digital gene
expression (DGE) system. Consequently, 11,913,548 transcriptome sequencing
reads were obtained. Finally, these reads were eventually assembled
into 37,218 unique unigenes. These assembled unigenes were annotated
with various methods. Transcriptome changes during planarian regeneration
were investigated by using a tag-based DGE system. We obtained a
sequencing depth of more than 3.5 million tags per sample and
identified a large number of differentially expressed genes at various
stages of regeneration. The results provide a fairly comprehensive
molecular biology background to the research on planarian development,
particularly with regard to its regeneration progress.},
doi = {10.1016/j.ygeno.2011.02.002},
issn = {0888-7543},
keywords = {Digital gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0888754311000218}
}
@ARTICLE{Qin2009a,
author = {Qin, Zhao and Barthel, Linda K. and Raymond, Pamela A.},
title = {Genetic evidence for shared mechanisms of epimorphic regeneration
in zebrafish},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {9310--9315},
number = {23},
month = jun,
abstract = {In a microarray-based gene profiling analysis of Muller glia-derived
retinal stem cells in light-damaged retinas from adult zebrafish,
we found that 2 genes required for regeneration of fin and heart
tissues in zebrafish, hspd1 (heat shock 60-kDa protein 1) and mps1
(monopolar spindle 1), were up-regulated. Expression of both genes
in the neurogenic Muller glia and progenitors was independently verified
by quantitative reverse transcriptase PCR and in situ hybridization.
Functional analysis of temperature-sensitive mutants of hspd1 and
mps1 revealed that both are necessary for Muller glia-based cone
photoreceptor regeneration in adult zebrafish retina. In the amputated
fin, hspd1 is required for the induction of mesenchymal stem cells
and blastema formation, whereas mps1 is required at a later step
for rapid cell proliferation and outgrowth. This temporal sequence
of hspd1 and mps1 function is conserved in the regenerating retina.
Comparison of gene expression profiles from regenerating zebrafish
retina, caudal fin, and heart muscle revealed additional candidate
genes potentially implicated in injury-induced epimorphic regeneration
in diverse zebrafish tissues.},
url = {http://www.pnas.org/cgi/content/abstract/106/23/9310}
}
@ARTICLE{Qin2008b,
author = {Qin, Zhenxia and Sun, Zhongwei and Huang, Jing and Hu, Yinghe and
Wu, Zirong and Mei, Bing},
title = {Mutated recombinant human glucagon-like peptide-1 protects SH-SY5Y
cells from apoptosis induced by amyloid-[beta] peptide (1-42)},
journal = {Neuroscience Letters},
year = {2008},
volume = {444},
pages = {217--221},
number = {3},
month = oct,
abstract = {Accumulation and deposition of amyloid [beta] peptide (A[beta]) in
the brain causes neuronal apoptosis and eventually leads to Alzheimer's
disease (AD). A therapeutic target for AD is to block the cascade
reaction induced by A[beta]. It has been demonstrated that glucagon-like
peptide-1 (GLP-1), which is an endogenous insulinotropic peptide
secreted from the gut, binds to its receptor in the brain and possesses
neuroprotective effects. Using site-directed mutagenesis and gene
recombination techniques, we generated a mutated recombinant human
glucagon-like peptide-1 (mGLP-1) which has longer half-life as compared
with native GLP-1. This present work aims to examine whether mGLP-1
attenuates A[beta]1-42-mediated cytotoxicity in SH-SY5Y cells and
to explore the possible mechanisms. Our data indicate that >=0.02 ng/ml
of mGLP-1 facilitated cell proliferation and 0.1 ng/ml and 0.5 ng/ml
of mGLP-1 rescued SH-SY5Y cells from A[beta]1-42-induced apoptosis.
Moreover, A[beta]1-42 treatment dramatically stimulated the release
of Ca2+ from internal calcium stores in SH-SY5Y cells, while mGLP-1
helped to maintain the intracellular Ca2+ homeostasis. A[beta]1-42
also significantly increased the expression level of TP53 and Bax
genes which are involved in apoptotic pathways, and mGLP-1 decreased
A[beta]1-42-induced up-regulation of TP53 and Bax. Since mGLP-1 treatment
elevated cytosolic cAMP concentration in SH-SY5Y cells, we postulate
that mGLP-1 may exert its influence via binding to GLP-1 receptors
in SH-SY5Y cells and stimulating the production of cAMP. These results
suggest that mGLP-1 exhibited neuronal protection properties, and
could potentially be a novel therapeutic agent for intervention in
Alzheimer's disease.},
issn = {0304-3940},
keywords = {Alzheimer's disease, Apoptosis, mGLP-1, A[beta]1-42, SH-SY5Y cells},
url = {http://www.sciencedirect.com/science/article/B6T0G-4T8JXJ9-5/2/b6c94176f98d46ecbf90e7c22367712a}
}
@ARTICLE{Qing2007,
author = {Qing, Guoliang and Qu, Zhaoxia and Xiao, Gutian},
title = {Endoproteolytic processing of C-terminally truncated NF-{kappa}B2
precursors at {kappa}B-containing promoters},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {5324--5329},
number = {13},
month = mar,
abstract = {The C-terminal, partially truncated forms of the NF-{kappa}B2/p52
precursor p100, p100{Delta}Cs, manifest constitutive processing and
oncogenic ability, although the responsible mechanisms remain unknown.
Here, we report that p100{Delta}Cs are specifically processed in
association with binding to promoter DNA-containing {kappa}B sites.
In the nucleus, p100{Delta}Cs bind to the {kappa}B promoter DNA and
subsequently recruit the proteasome to form a stable proteasome/p100{Delta}C/DNA
complex, which mediates the processing of p100{Delta}Cs. Notably,
the processing at the {kappa}B promoter is initiated by a proteasome-mediated
endoproteolytic cleavage at amino acid D415 of p100{Delta}Cs, and
the processed p52, but not the precursors themselves, is oncogenic
by up-regulating a subset of target genes. Our studies demonstrate
a different mechanism of p100 processing and also present evidence
showing that the proteasome modulates the action of transcription
factors at promoter regions through endoproteolysis.},
url = {http://www.pnas.org/cgi/content/abstract/104/13/5324}
}
@ARTICLE{Qiu2006,
author = {Qiu, Hong and Gabrielsen, Anders and Agardh, Hanna E. and Wan, Min
and Wetterholm, Anders and Wong, Chi-Huey and Hedin, Ulf and Swedenborg,
Jesper and Hansson, Goran K. and Samuelsson, Bengt and Paulsson-Berne,
Gabrielle and Haeggstrom, Jesper Z.},
title = {Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human
atherosclerotic lesions correlates with symptoms of plaque instability},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {8161--8166},
number = {21},
month = may,
abstract = {Leukotrienes (LT) are a group of proinflammatory lipid mediators that
are implicated in the pathogenesis and progression of atherosclerosis.
Here we report that mRNA levels for the three key proteins in LTB4
biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein
(FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in
human atherosclerotic plaque (n = 72) as compared with healthy controls
(n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits
significantly increased mRNA levels. Immunohistochemical staining
revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing
in macrophages of intimal lesions. Human lesion tissue converts arachidonic
acid into significant amounts of LTB4, and a selective, tight-binding
LTA4H inhibitor can block this activity. Furthermore, expression
of 5-LO and LTA4H, but not FLAP, is increased in patients with recent
or ongoing symptoms of plaque instability, and medication with warfarin
correlates with increased levels of FLAP mRNA. In contrast to human
plaques, levels of 5-LO mRNA are not significantly increased in plaque
tissues from two atherosclerosis-prone mouse strains, and mouse plaques
exhibit segregated cellular expression of LTA4H and 5-LO as well
as strong increases of CysLT1 and CysLT2 mRNA. These discrepancies
indicate that phenotypic changes in the synthesis and action of LT
in specific mouse models of atherosclerosis should be cautiously
translated into human pathology. The abundant expression of LTA4H
and correlation with plaque instability identify LTA4H as a potential
target for pharmacological intervention in treatment of human atherosclerosis.},
url = {http://www.pnas.org/cgi/content/abstract/103/21/8161}
}
@ARTICLE{Qiu2008,
author = {Qiu, Hong and Straat, Klas and Rahbar, Afsar and Wan, Min and Soderberg-Naucler,
Cecilia and Haeggstrom, Jesper Z.},
title = {Human CMV infection induces 5-lipoxygenase expression and leukotriene
B4 production in vascular smooth muscle cells},
journal = {J. Exp. Med.},
year = {2008},
volume = {205},
pages = {19--24},
number = {1},
month = jan,
abstract = {Leukotrienes (LTs) are powerful proinflammatory lipid mediators that
may play a central role in cardiovascular diseases, including arteriosclerosis,
myocardial infarction, and stroke. Owing to restricted expression
of 5-lipoxygenase (5-LO), the enzyme required for their synthesis,
LTs are almost exclusively produced by myeloid cells. Here, we report
that human cytomegalovirus (HCMV) infection of human vascular smooth
muscle cells (SMCs) increases 5-LO mRNA levels by up to 170-fold
in a dose- and time-dependent manner. Infected cells expressed 5-LO
protein, as shown by immunohistochemistry, enabling them to synthesize
bioactive LTB4. HCMV-infected vascular SMCs expressing 5-LO protein
were readily detected in tissue samples from CMV-infected patients
with inflammatory bowel disease or AIDS. Thus, pathogen-induced LT
production in HCMV-infected tissues may contribute to local inflammation,
consistent with the ability of HCMV to control cellular and immunological
functions. HCMV-induced LT biosynthesis in SMCs offers a molecular
mechanism to explain HCMV-induced pathogenesis in inflammatory diseases.},
url = {http://jem.rupress.org/cgi/content/abstract/205/1/19}
}
@ARTICLE{Qiu2010a,
author = {Qiu, J. and Jiang, Y. and Xia, L. and Xiang, H. and Feng, H. and
Pu, S. and Huang, N. and Yu, L. and Deng, X.},
title = {Subinhibitory concentrations of licochalcone A decrease alpha-toxin
production in both methicillin-sensitive and methicillin-resistant
Staphylococcus aureus isolates},
journal = {Letters in Applied Microbiology},
year = {2010},
volume = {50},
pages = {223--229},
number = {2},
abstract = {Abstract Aim:  To evaluate the effect of subinhibitory concentrations
of licochalcone A (LicA) on alpha-toxin secretion in Staphylococcus
aureus. Methods and Results:  A haemolysin assay was used to investigate
the haemolytic activities in culture supernatants of both methicillin-sensitive
and methicillin-resistant Staph. aureus isolates cultured with graded
subinhibitory concentrations of LicA. Alpha-toxin secretion was detected
by immunoblot analysis. Moreover, quantitative RT-PCR was performed
to assess the influence of LicA on the transcription of hla (the
gene encoding alpha-toxin) and agr (accessory gene regulator). Growth
in the presence of LicA markedly inhibited the mRNA levels of hla
and agr in Staph. aureus, resulting in a reduction of alpha-toxin
secretion and, thus, haemolytic activities. Conclusion:  The secretion
of alpha-toxin in Staph. aureus is decreased by LicA; this effect
may be partially dependent upon inhibition of the Agr two-component
system. Significance and Impact of the Study:  The findings in
our study may support the use of LicA as a lead compound in the design
of more potent antibacterial agents that are based on the chalcone
template.},
issn = {1472-765X},
keywords = {agr, alpha-toxin, haemolysis, licochalcone A, Staphylococcus aureus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1472-765X.2009.02783.x}
}
@ARTICLE{Qiu2011,
author = {Qiu, Jiazhang and Luo, Mingjing and Wang, Jianfeng and Dong, Jing
and Li, Hongen and Leng, Bingfeng and Zhang, Qian and Dai, Xiaohan
and Zhang, Yu and Niu, Xiaodi and Deng, Xuming},
title = {Isoalantolactone protects against Staphylococcus aureus pneumonia},
journal = {FEMS Microbiology Letters},
year = {2011},
volume = {324},
pages = {147--155},
number = {2},
abstract = {Staphylococcus aureus is a versatile pathogen that can cause life-threatening
infections. The growing emergence of methicillin-resistant S. aureus
strains and a decrease in the discovery of new antibiotics warrant
the search for new therapeutic targets to combat infections. Staphylococcus
aureus produces many extracellular virulence factors that contribute
to its pathogenicity. Therefore, targeting bacterial virulence as
an alternative strategy to the development of new antimicrobials
has gained great interest. α-Toxin is a 33.2-kDa, water-soluble,
pore-forming toxin that is secreted by most S. aureus strains. α-Toxin
is essential for the pathogenesis of pneumonia, as strains lacking
α-toxin display a profound defect in virulence. In this report,
we demonstrate that isoalantolactone (IAL), a naturally occurring
compound found in Inula helenium (Compositae), has no anti-S. aureus
activity as per MIC evaluation in vitro. However, IAL can markedly
inhibit the expression of α-toxin in S. aureus at very low concentrations.
Furthermore, the in vivo data indicate that treatment with IAL protects
mice from S. aureus pneumonia.},
doi = {10.1111/j.1574-6968.2011.02397.x},
issn = {1574-6968},
keywords = {isoalantolactone, Staphylococcus aureus, α-toxin, pneumonia, antivirulence},
url = {http://dx.doi.org/10.1111/j.1574-6968.2011.02397.x}
}
@ARTICLE{Qiu2011a,
author = {Qiu, Qiang and Ma, Tao and Hu, Quanjun and Liu, Bingbing and Wu,
Yuxia and Zhou, Haihong and Wang, Qian and Wang, Juan and Liu, Jianquan},
title = {Genome-scale transcriptome analysis of the desert poplar, Populus
euphratica},
journal = {Tree Physiol},
year = {2011},
volume = {31},
pages = {452--461},
number = {4},
month = apr,
abstract = {Populus euphratica is well-adapted to extreme desert environments
and is an important model species for studying the effects of abiotic
stresses on trees. Here we present the first deep transcriptomic
analysis of this species. To maximize representation of conditional
transcripts, mRNA was obtained from living tissues of desert-grown
trees and two types of callus (salt-stressed and unstressed). De
novo assembly generated 86,777 Unigenes using Solexa sequence data.
These sequences covered 92% of previously reported P. euphratica
expressed sequence tags (ESTs) and 90% of the TIGR poplar ESTs, and
a total of 58,499 high-quality unique sequences were annotated by
BLAST similarity searches against public databases. We found that
27% of the total Unigenes were differentially expressed (up- or down-regulated)
in response to salt stress in P. euphratica callus. These differentially
expressed genes are mainly involved in transport, transcription,
cellular communication and metabolism. In addition, we found that
numerous putative genes involved in ABA regulation and biosynthesis
were also differentially regulated. This study represents the deepest
transcriptomic and gene-annotation analysis of P. euphratica to date.
The genetic knowledge acquired should be very useful for future studies
of the molecular adaptation of this tree species to abiotic stress
and facilitate genetic manipulation of other poplar species.},
comment = {10.1093/treephys/tpr015},
url = {http://treephys.oxfordjournals.org/cgi/content/abstract/31/4/452}
}
@ARTICLE{Qiu2010,
author = {Qiu, Weimin and Hu, Yuhui and Andersen, Tom E. and Jafari, Abbas
and Li, Na and Chen, Wei and Kassem, Moustapha},
title = {Tumor Necrosis Factor Receptor Superfamily Member 19 (TNFRSF19) Regulates
Differentiation Fate of Human Mesenchymal (Stromal) Stem Cells through
Canonical Wnt Signaling and C/EBP},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {14438--14449},
number = {19},
month = may,
abstract = {Mechanisms controlling human multipotent mesenchymal (stromal) stem
cell (hMSC) differentiation into osteoblasts or adipocytes are poorly
understood. We have previously demonstrated that Wnt signaling in
hMSC enhanced osteoblast differentiation and inhibited adipogenesis
by comparing two hMSC cell lines overexpressing mutated forms of
the Wnt co-receptor LRP5: T253I (hMSC-LRP5T253) and T244M (hMSC-LRP5T244)
conducting high and low level of Wnt signaling, respectively. To
explore the underlying molecular mechanisms, we compared gene expression
profiles of hMSC-LRP5T253 and hMSC-LRP5T244 treated with Wnt3a using
whole genome expression microarrays and found that TNFRSF19 is differentially
up-regulated between the two cells lines. Bioinformatic analysis
and dual luciferase assay of its promoter revealed that TNFRSF19
transcript 2 (TNFRSF19.2) is a target of canonical Wnt signaling.
Knocking down TNFRSF19 in hMSC-LRP5T253 cells decreased Wnt3a-induced
osteoblast differentiation marker alkaline phosphate activity and
its overexpression in hMSC-LRP5T244 cells increased alkaline phosphate
activity. In addition, TNFRSF19 was negatively regulated by adipogenic
transcription factor CCAAT/enhancer-binding proteins (C/EBP). Knocking
down TNFRSF19 in hMSC-LRP5T253 cells or its overexpression in hMSC-LRP5T244
cells significantly increased or decreased adipogenesis, respectively.
In conclusion, we revealed a novel function of TNFRSF19 as a factor
mediating differentiation signals that determine the hMSC differentiating
fate into osteoblasts or adipocytes.},
url = {http://www.jbc.org/cgi/content/abstract/285/19/14438}
}
@ARTICLE{Qu2009,
author = {Qu, Xian and Mazéas, Laurent and Vavilin, Vasily A. and Epissard,
Jonathan and Lemunier, Mélanie and Mouchel, Jean-Marie and He, Pin-jing
and Bouchez, Théodore},
title = {Combined monitoring of changes in δ13CH4 and archaeal community
structure during mesophilic methanization of municipal solid waste},
journal = {FEMS Microbiology Ecology},
year = {2009},
volume = {68},
pages = {236--245},
number = {2},
abstract = {Abstract Reconstituted municipal solid waste (MSW) with varying contents
of putrescible and cellulosic waste was incubated anaerobically under
mesophilic conditions. Standard physicochemical parameters were monitored,
together with stable isotopic signatures of produced CH4 and CO2.
δ13C values for CH4 indicated a change of methanogenic metabolism
with time. CH4 was predominantly produced from H2/CO2 at the beginning
of the incubations. This period was associated with important shifts
in archaeal communities monitored by automated ribosomal intergenic
spacer analysis (ARISA) and FISH of oligonucleotidic probes targeting
specifically 16S rRNA gene of various methanogenic groups. The onset
of the active methane generation phase was characterized by an increase
of CH4δ13C, indicating a progressive shift toward an aceticlastic
metabolism. When the methane production levelled off, a decrease
in the isotopic signature was observed toward values characteristics
of hydrogenotrophic metabolism. ARISA profiles were, however, found
to be stable from the beginning of the active methane generation
phase until the end of the experiment. FISH observation indicated
that members of the family Methanosarcinaceae were predominant in
the archaeal community during this period, suggesting that these
methanogens might exhibit a high metabolic versatility during methanization
of waste.},
issn = {1574-6941},
keywords = {municipal solid waste, methanization, stable carbon isotopic signature,
automated ribosomal intergenic spacer analysis, FISH},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6941.2009.00661.x}
}
@ARTICLE{Qu2011,
author = {Qu, Zhaoxia and Sun, Dongming and Young, Wise},
title = {Lithium promotes neural precursor cell proliferation: evidence for
the involvement of the non-canonical GSK-3beta-NF-AT signaling},
journal = {Cell \& Bioscience},
year = {2011},
volume = {1},
pages = {18},
number = {1},
abstract = {Lithium, a drug that has long been used to treat bipolar disorder
and some other human pathogenesis, has recently been shown to stimulate
neural precursor growth. However, the involved mechanism is not clear.
Here, we show that lithium induces proliferation but not survival
of neural precursor cells. Mechanistic studies suggest that the effect
of lithium mainly involved activation of the transcription factor
NF-AT and specific induction of a subset of proliferation-related
genes. While NF-AT inactivation by specific inhibition of its upstream
activator calcineurin antagonized the effect of lithium on the proliferation
of neural precursor cells, specific inhibition of the NF-AT inhibitor
GSK-3beta, similar to lithium treatment, promoted neural precursor
cell proliferation. One important function of lithium appeared to
increase inhibitory phosphorylation of GSK-3beta, leading to GSK-3beta
suppression and subsequent NF-AT activation. Moreover, lithium-induced
proliferation of neural precursor cells was independent of its role
in inositol depletion. These findings not only provide mechanistic
insights into the clinical effects of lithium, but also suggest an
alternative therapeutic strategy for bipolar disorder and other neural
diseases by targeting the non-canonical GSK-3beta-NF-AT signaling.},
doi = {10.1186/2045-3701-1-18},
issn = {2045-3701},
pubmedid = {21711903},
url = {http://www.cellandbioscience.com/content/1/1/18}
}
@ARTICLE{Quach2009,
author = {Quach, Darin and van Sorge, Nina M. and Kristian, Sascha A. and Bryan,
Joshua D. and Shelver, Daniel W. and Doran, Kelly S.},
title = {The CiaR Response Regulator in Group B Streptococcus Promotes Intracellular
Survival and Resistance to Innate Immune Defenses},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {2023--2032},
number = {7},
month = apr,
abstract = {Group B Streptococcus (GBS) is major cause of invasive disease in
newborn infants and the leading cause of neonatal meningitis. To
gain access to the central nervous system (CNS), GBS must not only
subvert host defenses in the bloodstream but also invade and survive
within brain microvascular endothelial cells (BMEC), the principal
cell layer composing the blood-brain barrier (BBB). While several
GBS determinants that contribute to the invasion of BMEC have been
identified, little is known about the GBS factors that are required
for intracellular survival and ultimate disease progression. In this
study we sought to identify these factors by screening a random GBS
mutant library in an in vitro survival assay. One mutant was identified
which contained a disruption in a two-component regulatory system
homologous to CiaR/CiaH, which is present in other streptococcal
pathogens. Deletion of the putative response regulator, ciaR, in
GBS resulted in a significant decrease in intracellular survival
within neutrophils, murine macrophages, and human BMEC, which was
linked to increased susceptibility to killing by antimicrobial peptides,
lysozyme, and reactive oxygen species. Furthermore, competition experiments
with mice showed that wild-type GBS had a significant survival advantage
over the GBS {Delta}ciaR mutant in the bloodstream and brain. Microarray
analysis comparing gene expression between wild-type and {Delta}ciaR
mutant GBS bacteria revealed several CiaR-regulated genes that may
contribute to stress tolerance and the subversion of host defenses
by GBS. Our results identify the GBS CiaR response regulator as a
crucial factor in GBS intracellular survival and invasive disease
pathogenesis.},
url = {http://jb.asm.org/cgi/content/abstract/191/7/2023}
}
@BOOK{Quail2001,
title = {Improved Protocols for the Illumina Genome Analyzer Sequencing System},
publisher = {John Wiley \& Sons, Inc.},
year = {2001},
author = {Quail, Michael A. and Swerdlow, Harold and Turner, Daniel J.},
pages = {--},
abstract = {In this unit, we describe a set of improvements we have made to the
standard Illumina Genome Analyzer protocols to make the sequencing
process more reliable in a high-throughput environment, reduce amplification
bias, narrow the distribution of insert sizes, and reliably obtain
high yields of data. Curr. Protoc. Hum. Genet. 62:18.2.1-18.2.27.
© 2009 by John Wiley & Sons, Inc.},
booktitle = {Current Protocols in Human Genetics},
issn = {9780471142904},
keywords = {Illumina, Next-Generation, sequencer, protocols, Genome Analyzer},
url = {http://dx.doi.org/10.1002/0471142905.hg1802s62}
}
@ARTICLE{Quan2011,
author = {Quan, Shu and Koldewey, Philipp and Tapley, Tim and Kirsch, Nadine
and Ruane, Karen M and Pfizenmaier, Jennifer and Shi, Rong and Hofmann,
Stephan and Foit, Linda and Ren, Guoping and Jakob, Ursula and Xu,
Zhaohui and Cygler, Miroslaw and Bardwell, James C A},
title = {Genetic selection designed to stabilize proteins uncovers a chaperone
called Spy},
journal = {Nat Struct Mol Biol},
year = {2011},
volume = {18},
pages = {262--269},
number = {3},
month = mar,
comment = {10.1038/nsmb.2016},
issn = {1545-9993},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nsmb.2016}
}
@ARTICLE{Quaresima2008,
author = {Quaresima, Barbara and Romeo, Francesco and Faniello, Maria C. and
Di Sanzo, Maddalena and Liu, Chang-Gong and Lavecchia, Annamaria
and Taccioli, Cristian and Gaudio, Eugenio and Baudi, Francesco and
Trapasso, Francesco and Croce, Carlo M. and Cuda, Giovanni and Costanzo,
Francesco},
title = {BRCA1 5083del19 Mutant Allele Selectively Up-Regulates Periostin
Expression In vitro and In vivo},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6797--6803},
number = {21},
month = nov,
abstract = {Purpose: The aim of this study was to explore the gene expression
pattern produced by the cancer-associated BRCA1 5083del19 founder
mutation by using a microarray analysis. Such a mutation, identified
in a subset of familial breast cancer patients, involves a deletion
at the 3' end of the BRCA1 messenger leading, in the mature protein,
to the ablation of the BRCT tandem domain. Experimental Design: We
generated HeLa cells stably expressing both exogenous wild-type (HeLa/wtBRCA1),
used as a control, and 5083del19 BRCA1 (HeLa/5083del19BRCA1) alleles;
gene chips were then used to investigate any changes in the transcription
profile induced by the 5083del19 BRCA1 mutant compared with controls.
Results: Among the genes showing perturbation of their expression,
periostin was found to be up-regulated in HeLa/5083del19BRCA1 cells
to an extent of 72-fold versus HeLa/pcDNA3.1/empty and 76-fold versus
HeLa/wtBRCA1 cells. This finding was validated both in vitro in breast
cancer cell lines harboring mutations of BRCA1 and in vivo by immunohistochemistry
of breast cancer specimens bearing the 5083del19 BRCA1 mutation as
well as by Western blot analysis of sera obtained from patients and
healthy carriers of the same mutation. Conclusions: Our results suggest
that periostin overexpression, whose product is released from cells
in the extracellular fluids, might be a potential marker for early
cancer detection in a specific subset of hereditary breast carcinomas
triggered by cancer-associated BRCA1 mutations that affect the BRCT
tandem domain.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/21/6797}
}
@ARTICLE{Quebatte2010,
author = {Quebatte, Maxime and Dehio, Michaela and Tropel, David and Basler,
Andrea and Toller, Isabella and Raddatz, Guenter and Engel, Philipp
and Huser, Sonja and Schein, Hermine and Lindroos, Hillevi L. and
Andersson, Siv G. E. and Dehio, Christoph},
title = {The BatR/BatS Two-Component Regulatory System Controls the Adaptive
Response of Bartonella henselae during Human Endothelial Cell Infection},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {3352--3367},
number = {13},
month = jul,
abstract = {Here, we report the first comprehensive study of Bartonella henselae
gene expression during infection of human endothelial cells. Expression
of the main cluster of upregulated genes, comprising the VirB type
IV secretion system and its secreted protein substrates, is shown
to be under the positive control of the transcriptional regulator
BatR. We demonstrate binding of BatR to the promoters of the virB
operon and a substrate-encoding gene and provide biochemical evidence
that BatR and BatS constitute a functional two-component regulatory
system. Moreover, in contrast to the acid-inducible (pH 5.5) homologs
ChvG/ChvI of Agrobacterium tumefaciens, BatR/BatS are optimally activated
at the physiological pH of blood (pH 7.4). By conservation analysis
of the BatR regulon, we show that BatR/BatS are uniquely adapted
to upregulate a genus-specific virulence regulon during hemotropic
infection in mammals. Thus, we propose that BatR/BatS two-component
system homologs represent vertically inherited pH sensors that control
the expression of horizontally transmitted gene sets critical for
the diverse host-associated life styles of the alphaproteobacteria.},
url = {http://jb.asm.org/cgi/content/abstract/192/13/3352}
}
@ARTICLE{Queiroz2009,
author = {Queiroz, Rafael and Benz, Corinna and Fellenberg, Kurt and Hoheisel,
Jörg and Clayton, Christine},
title = {Transcriptome analysis of differentiating trypanosomes reveals the
existence of multiple post-transcriptional regulons},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {495},
number = {1},
abstract = {BACKGROUND:Trypanosome gene expression is regulated almost exclusively
at the post-transcriptional level, with mRNA degradation playing
a decisive role. When trypanosomes are transferred from the blood
of a mammal to the midgut of a Tsetse fly, they transform to procyclic
forms: gene expression is reprogrammed, changing the cell surface
and switching the mode of energy metabolism. Within the blood, trypanosomes
can pre-adapt for Tsetse transmission, becoming growth-arrested stumpy
forms. We describe here the transitions in gene expression that occur
during differentiation of in-vitro cultured bloodstream forms to
procyclic forms.RESULTS:Some mRNAs showed changes within 30 min of
cis-aconitate addition, whereas others responded 12-24 hours later.
For the first 12 h after addition of cis-aconitate, cells accumulated
at the G1 phase of the cell cycle, and showed decreases in mRNAs
required for proliferation, mimicking the changes seen in stumpy
forms: many mRNAs needed for ribosomal and flagellar biogenesis showed
striking co-regulation. Other mRNAs encoding components of signal
transduction pathways and potential regulators were specifically
induced only during differentiation. Messenger RNAs encoding proteins
required for individual metabolic pathways were often co-regulated.CONCLUSION:Trypanosome
genes form post-transcriptional regulons in which mRNAs with functions
in particular pathways, or encoding components of protein complexes,
show almost identical patterns of regulation.},
doi = {10.1186/1471-2164-10-495},
issn = {1471-2164},
pubmedid = {19857263},
url = {http://www.biomedcentral.com/1471-2164/10/495}
}
@ARTICLE{Quere2011,
author = {Quere, R and Andradottir, S and Brun, A C M and Zubarev, R A and
Karlsson, G and Olsson, K and Magnusson, M and Cammenga, J and Karlsson,
S},
title = {High levels of the adhesion molecule CD44 on leukemic cells generate
acute myeloid leukemia relapse after withdrawal of the initial transforming
event},
journal = {Leukemia},
year = {2011},
volume = {25},
pages = {515--526},
number = {3},
month = mar,
issn = {0887-6924},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/leu.2010.281}
}
@ARTICLE{Quere2007,
author = {Quere, Ronan and Baudet, Aurelie and Cassinat, Bruno and Bertrand,
Gerald and Marti, Jacques and Manchon, Laurent and Piquemal, David
and Chomienne, Christine and Commes, Therese},
title = {Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights
CYP26 cytochrome metabolism in differential all-trans retinoic acid
sensitivity},
journal = {Blood},
year = {2007},
volume = {109},
pages = {4450--4460},
number = {10},
month = may,
abstract = {Disease relapse sometimes occurs after acute promyelocytic leukemia
(APL) therapy with all-trans retinoic acid (ATRA). Among the diagnostic
parameters predicting relapse, heterogeneity in the in vitro differentiation
rate of blasts is an independent factor. To identify biologic networks
involved in resistance, we conducted pharmacogenomic studies in APL
blasts displaying distinct ATRA sensitivities. Although the expression
profiles of genes invested in differentiation were similarly modulated
in low- and high-sensitive blasts, low-sensitive cells showed higher
levels of transcription of ATRA-target genes, transcriptional regulators,
chromatin remodelers, and transcription factors. In opposition, only
high-sensitive blasts expressed the CYP26A1 gene, encoding the p450
cytochrome which is known to be involved in retinoic acid catabolism.
In NB4 cells, ATRA treatment activates a novel signaling pathway,
whereby interleukin-8 stimulates the expression of the homeobox transcription
factor HOXA10v2, an effective enhancer of CYP26A1 transcription.
These data were corroborated in primary APL cells, as maturation
levels correlated with CYP26A1 expression. Treatment with a retinoic
acid metabolism blocking agent (RAMBA) results in high-nucleoplasmic
concentrations of retinoid and growth of NB4-resistant subclones.
Hence, for APL blasts associated with poor prognosis, the low CYP26A1
expression may explain high risk of resistance installation, by increased
retinoid pressure. Pharmacogenomic profiles of genes involved in
retinoid acid metabolism may help to optimize anticancer therapies,
including retinoids.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/10/4450}
}
@ARTICLE{Quesada2011,
author = {Quesada, Isabel M. and Bustos, Mario and Blay, Mayte and Pujadas,
Gerard and Ardèvol, Anna and Salvadó, M. Josepa and Bladé, Cinta
and Arola, Lluís and Fernández-Larrea, Juan},
title = {Dietary catechins and procyanidins modulate zinc homeostasis in human
HepG2 cells},
journal = {The Journal of Nutritional Biochemistry},
year = {2011},
volume = {22},
pages = {153--163},
number = {2},
month = feb,
abstract = {Catechins and their polymers procyanidins are health-promoting flavonoids
found in edible vegetables and fruits. They act as antioxidants by
scavenging reactive oxygen species and by chelating the redox-active
metals iron and copper. They also behave as signaling molecules,
modulating multiple cell signalling pathways and gene expression,
including that of antioxidant enzymes. This study aimed at determining
whether catechins and procyanidins interact with the redox-inactive
metal zinc and at assessing their effect on cellular zinc homeostasis.
We found that a grape-seed procyanidin extract (GSPE) and the green
tea flavonoid (-)-epigallocatechin-3-gallate (EGCG) bind zinc cations
in solution with higher affinity than the zinc-specific chelator
Zinquin, and dose-dependently prevent zinc-induced toxicity in the
human hepatocarcinoma cell line HepG2, evaluated by the lactate dehydrogenase
test. GSPE and EGCG hinder intracellular accumulation of total zinc,
measured by atomic flame absorption spectrometry, concomitantly increasing
the level of cytoplasmic labile zinc detectable by Zinquin fluorescence.
Concurrently, GSPE and EGCG inhibit the expression, evaluated at
the mRNA level by quantitative reverse transcriptase-polymerase chain
reaction, of zinc-binding metallothioneins and of plasma membrane
zinc exporter ZnT1 (SLC30A1), while enhancing the expression of cellular
zinc importers ZIP1 (SLC39A1) and ZIP4 (SLC39A4). GSPE and EGCG also
produce all these effects when HepG2 cells are stimulated to import
zinc by treatment with supplemental zinc or the proinflammatory cytokine
interleukin-6. We suggest that extracellular complexation of zinc
cations and the elevation of cytoplasmic labile zinc may be relevant
mechanisms underlying the modulation of diverse cell signaling and
metabolic pathways by catechins and procyanidins.},
issn = {0955-2863},
keywords = {Epigallocatechin gallate, Procyanidins, Flavonoids, Labile zinc, Metallothionein,
Zinc transporters},
url = {http://www.sciencedirect.com/science/article/pii/S0955286310000343}
}
@ARTICLE{Quesnell2012,
author = {R.R. Quesnell and S. Klaessig and J.L. Watts and Y.H. Schukken},
title = {Bovine intramammary Escherichia coli challenge infections in late
gestation demonstrate a dominant antiinflammatory immunological response},
journal = {Journal of Dairy Science},
year = {2012},
volume = {95},
pages = {117 - 126},
number = {1},
abstract = {Coliform mastitis that presents itself at parturition or in the early
weeks of bovine lactation is often characterized by severe inflammation
and impaired milk production and can lead to death of the animal.
Chronic intramammary infections caused by persistent strains of Escherichia
coli may result in high production losses. The aim of this study
was to determine the inflammatory response to a teat-canal challenge
of bovine mammary glands with a persistent strain of E. coli during
late gestation (dry period) and into early lactation. Two weeks before
parturition, animals were challenged in 2 quarters with 30 cfu of
a persistent strain of E. coli; control quarters were vehicle-infused
and not infused, respectively. Samples of dry cow secretions were
taken from all quarters before challenge and at 6, 12, 18, 24, 48,
72, 96, and 120 h following challenge. Colostrum samples and
milk samples were taken from all quarters at parturition and 6, 12,
18, 24, 48, 72, 96 and 120 h postpartum. Bacterial culture,
combined with random amplified polymorphic DNA genetic strain-typing
analysis, indicated recovery of the bacterial challenge strain until
48 to 96 h postchallenge, and again at parturition and up to
6 and 12 h postpartum. One animal exhibited clinical mastitis
and the bacterial challenge strain was evident to at least 12 d postpartum.
During twice-daily milkings, production levels were lower in bacteria-challenged
quarters compared with controls. Somatic cell counts decreased to
normal levels at a slower rate in challenged quarters compared with
control quarters. Cytokine analysis indicated a minimal proinflammatory
cytokine response, including interleukin-1β and tumor necrosis factor-α
in challenged-quarter dry cow samples up to 120 h postchallenge.
Interleukin-10 levels were significantly increased by 12 h postchallenge
in secretions from challenged and control quarters. These preliminary
results in 2 cows indicate that proinflammatory signaling after intramammary
bacterial infection may be actively suppressed during late gestation.
We hypothesize that this immune-inhibitory response allows intramammary
infections to become persistent in the dry period and cause clinical
signs immediately after parturition.},
doi = {10.3168/jds.2011-4289},
issn = {0022-0302},
keywords = {coliform mastitis},
url = {http://www.sciencedirect.com/science/article/pii/S0022030211006837}
}
@ARTICLE{Quignodon2007,
author = {Quignodon, Laure and Vincent, Severine and Winter, Harald and Samarut,
Jacques and Flamant, Frederic},
title = {A Point Mutation in the Activation Function 2 Domain of Thyroid Hormone
Receptor {alpha}1 Expressed after CRE-Mediated Recombination Partially
Recapitulates Hypothyroidism},
journal = {Mol. Endocrinol.},
year = {2007},
volume = {21},
pages = {2350--2360},
number = {10},
month = oct,
abstract = {Thyroid hormones act directly on transcription by binding to TR{alpha}1,
TR{beta}1, and TR{beta}2 nuclear receptors, regulating many aspects
of postnatal development and homeostasis. To analyze precisely the
implication of the widely expressed TR{alpha}1 isoform in this pleiotropic
action, we have generated transgenic mice with a point mutation in
the TR{alpha}1 coding sequence, which is expressed only after CRE/loxP-mediated
DNA recombination. The amino acid change prevents interaction between
TR{alpha}1 and histone acetyltransferase coactivators and the release
of corepressors. Early expression of this dominant-negative receptor
deeply affects postnatal development and adult homeostasis, recapitulating
many aspects of congenital and adult hypothyroidism, except in tissues
and cells where TR{beta}1 and TR{beta}2 are predominantly expressed.
Both respective abundance and intrinsic properties of TR{alpha}1
and TR{beta}1/2 seem to govern specificity of action.},
url = {http://mend.endojournals.org/cgi/content/abstract/21/10/2350}
}
@ARTICLE{Quiles2009,
author = {Quiles, Ignacio and Millan-Arino, Lluis and Subtil-Rodriguez, Alicia
and Minana, Belen and Spinedi, Nora and Ballare, Cecilia and Beato,
Miguel and Jordan, Albert},
title = {Mutational Analysis of Progesterone Receptor Functional Domains in
Stable Cell Lines Delineates Sets of Genes Regulated by Different
Mechanisms},
journal = {Mol. Endocrinol.},
year = {2009},
volume = {23},
pages = {809--826},
number = {6},
month = jun,
abstract = {Steroid hormone receptors act directly in the nucleus on the chromatin
organization and transcriptional activity of several promoters. Furthermore,
they have an indirect effect on cytoplasmic signal transduction pathways,
including MAPK, impacting ultimately on gene expression. We are interested
in distinguishing between the two modes of action of progesterone
receptor (PR) on the control of gene expression and cell proliferation.
For this, we have stably expressed, in PR-negative breast cancer
cells, tagged forms of the PR isoform B mutated at regions involved
either in DNA binding (DNA-binding domain) or in its ability to interact
with the estrogen receptor and to activate the c-Src/MAPK/Erk/Msk
cascade (estrogen receptor-interacting domain). Both mutants impair
PR-mediated activation of a well-understood model promoter in response
to progestin, as well as hormone-induced cell proliferation. Additional
mutants affecting transactivation activity of PR (activation function
2) or a zinc-finger implicated in dimerization (D-box) have also
been tested. Microarrays and gene expression experiments on these
cell lines define the subsets of hormone-responsive genes regulated
by different modes of action of PR isoform B, as well as genes in
which the nuclear and nongenomic pathways cooperate. Correlation
between CCND1 expression in the different cell lines and their ability
to support cell proliferation confirms CCND1 as a key controller
gene.},
url = {http://mend.endojournals.org/cgi/content/abstract/23/6/809}
}
@ARTICLE{Quina2009,
author = {Quina, Lely A. and Wang, Shirong and Ng, Lydia and Turner, Eric E.},
title = {Brn3a and Nurr1 Mediate a Gene Regulatory Pathway for Habenula Development},
journal = {J. Neurosci.},
year = {2009},
volume = {29},
pages = {14309--14322},
number = {45},
month = nov,
abstract = {The habenula is a dorsal diencephalic structure consisting of medial
and lateral subnuclei and a principal output tract, the fasciculus
retroflexus, which together form a link between the limbic forebrain
and ventral midbrain. Here, we have used microarray and bioinformatic
approaches in the mouse to show that the habenula is a distinctive
molecular territory of the CNS, with a unique profile of neurotransmitter,
ion channel, and regulatory factor expression. Neurons of the medial
habenula and part of the lateral habenula express the transcription
factor Brn3a/Pou4f1, and Brn3a-expressing habenular neurons project
exclusively to the interpeduncular nucleus in the ventral midbrain.
In Brn3a mutant embryos, the fasciculus retroflexus is directed appropriately,
but habenular neurons fail to innervate their targets. Microarray
analysis of Brn3a null embryos shows that this factor regulates an
extensive program of habenula-enriched genes, but not generic neural
properties. The orphan nuclear receptor Nurr1/Nr4a2 is coexpressed
with Brn3a in the developing habenula, is downstream of Brn3a, and
mediates expression of a subset of Brn3a-regulated transcripts. Together,
these findings begin to define a gene regulatory pathway for habenula
development in mammals.},
url = {http://www.jneurosci.org/cgi/content/abstract/29/45/14309}
}
@ARTICLE{Quinet2009,
author = {Quinet, Elaine M. and Basso, Michael D. and Halpern, Anita R. and
Yates, David W. and Steffan, Robert J. and Clerin, Valerie and Resmini,
Christine and Keith, James C. and Berrodin, Thomas J. and Feingold,
Irene and Zhong, Wenyan and Hartman, Helen B. and Evans, Mark J.
and Gardell, Stephen J. and DiBlasio-Smith, Elizabeth and Mounts,
William M. and LaVallie, Edward R. and Wrobel, Jay and Nambi, Ponnal
and Vlasuk, George P.},
title = {LXR ligand lowers LDL cholesterol in primates, is lipid neutral in
hamster, and reduces atherosclerosis in mouse},
journal = {J. Lipid Res.},
year = {2009},
volume = {50},
pages = {2358--2370},
number = {12},
month = dec,
abstract = {Liver X receptors (LXRs) are ligand-activated transcription factors
that coordinate regulation of gene expression involved in several
cellular functions but most notably cholesterol homeostasis encompassing
cholesterol transport, catabolism, and absorption. WAY-252623 (LXR-623)
is a highly selective and orally bioavailable synthetic modulator
of LXR, which demonstrated efficacy for reducing lesion progression
in the murine LDLR-/- atherosclerosis model with no associated increase
in hepatic lipogenesis either in this model or Syrian hamsters. In
nonhuman primates with normal lipid levels, WAY-252623 significantly
reduced total (50-55%) and LDL-cholesterol (LDLc) (70-77%) in a time-
and dose-dependent manner as well as increased expression of the
target genes ABCA1/G1 in peripheral blood cells. Statistically significant
decreases in LDLc were noted as early as day 7, reached a maximum
by day 28, and exceeded reductions observed for simvastatin alone
(20 mg/kg). Transient increases in circulating triglycerides and
liver enzymes reverted to baseline levels over the course of the
study. Complementary microarray analysis of duodenum and liver gene
expression revealed differential activation of LXR target genes and
suggested no direct activation of hepatic lipogenesis.},
url = {http://www.jlr.org/cgi/content/abstract/50/12/2358}
}
@ARTICLE{Quinn2009,
author = {Quinn, Michael C.J. and Filali-Mouhim, Abdelali and Provencher, Diane
M. and Mes-Masson, Anne-Marie and Tonin, Patricia N.},
title = {Reprogramming of the transcriptome in a novel chromosome 3 transfer
tumor suppressor ovarian cancer cell line model affected molecular
networks that are characteristic of ovarian cancer},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {648--661},
number = {7},
abstract = {Abstract 10.1002/mc.20511.abs Tumor suppression as a consequence of
the transfer of chromosome 3p fragments was previously observed in
a novel epithelial ovarian cancer (EOC) OV-90 cell line model harboring
loss of 3p. Microarray analysis revealed that tumor suppression was
associated with a modified transcriptome. To investigate the relevance
of the altered transcriptome, the differentially expressed genes
identified by Affymetrix analysis in the 3p transfer studies, were
integrated with a comparative microarray analysis of normal ovarian
surface epithelial (NOSE) cells and malignant ovarian (TOV) cancers.
Data from 219 significantly differentially expressed genes exhibited
patterns in the direction predicted by the analysis of 3p transfer
study. The 30 genes with the highest statistically significant differences
(P < 1 × 10−8) in expression were found consistently differentially
expressed between NOSE and TOV samples. The investigation of these
genes in benign serous ovarian tumors and EOC cell lines also exhibited
predictable expression patterns. Within the group of differentially
expressed genes were SPARC, DAB2, CP, EVI1, ELF3, and EHD2, known
to play a role in ovarian cancer, genes implicated in other cancers,
such as GREM1 and GLIPR1, as well as genes not previously reported
in a cancer context such as AKAP2 and ATAD4. A number of the differentially
expressed genes are implicated in the TGF-beta signaling pathway.
These findings suggest that the reprogramming of the transcriptome
that occurred as a consequence of the chromosome 3 transfer and tumor
suppression affected molecular networks that are characteristic of
ovarian carcinogenesis thus validating our novel ovarian cancer cell
line model. © 2009 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {serous ovarian cancer, microarray, tumor suppressor gene, benign ovarian
cancer, chromosome 3},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20511}
}
@ARTICLE{Quintin2009,
author = {Quintin, Aurelie and Schizas, Constantin and Scaletta, Corinne and
Jaccoud, Sandra and Gerber, Stefan and Osterheld, Maria-Chiara and
Juillerat, Lucienne and Applegate, Lee Ann and Pioletti, Dominique
P.},
title = {Isolation and in vitro chondrogenic potential of human foetal spine
cells},
journal = {Journal of Cellular and Molecular Medicine},
year = {2009},
volume = {13},
pages = {2559--2569},
number = {8b},
abstract = {Abstract Cell therapy for nucleus pulposus (NP) regeneration is an
attractive treatment for early disc degeneration as shown by studies
using autologous NP cells or stem cells. Another potential source
of cells is foetal cells. We investigated the feasibility of isolating
foetal cells from human foetal spine tissues and assessed their chondrogenic
potential in alginate bead cultures. Histology and immunohistochemistry
of foetal tissues showed that the structure and the matrix composition
(aggrecan, type I and II collagen) of foetal intervertebral disc
(IVD) were similar to adult IVD. Isolated foetal cells were cultured
in monolayer in basic media supplemented with 10% Fetal Bovine Serum
(FBS) and from each foetal tissue donation, a cell bank of foetal
spine cells at passage 2 was established and was composed of around
2000 vials of 5 million cells. Gene expression and immunohistochemistry
of foetal spine cells cultured in alginate beads during 28 days showed
that cells were able to produce aggrecan and type II collagen and
very low level of type I and type X collagen, indicating chondrogenic
differentiation. However variability in matrix synthesis was observed
between donors. In conclusion, foetal cells could be isolated from
human foetal spine tissues and since these cells showed chondrogenic
potential, they could be a potential cell source for IVD regeneration.},
issn = {1582-4934},
keywords = {foetal cells, intervertebral disc, cell therapy, alginate beads, extracellular
matrix},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2008.00630.x}
}
@ARTICLE{Quist2011,
author = {Quist, Jos and Janssen, Kjeld G. H. and Vulto, Paul and Hankemeier,
Thomas and van der Linden, Heiko J.},
title = {Single-Electrolyte Isotachophoresis Using a Nanochannel-Induced Depletion
Zone},
journal = {Analytical Chemistry},
year = {2011},
volume = {83},
pages = {7910-7915},
number = {20},
abstract = { Isotachophoretic separations are triggered at the border of a nanochannel-induced
ion-depleted zone. This depletion zone acts as a terminating electrolyte
and is created by concentration polarization over the nanochannel.
We show both continuous and discrete sample injections as well as
separation of up to four analytes. Continuous injection of a spacer
compound was used for selective analyte elution. Zones were kept
focused for over one hour, while shifting less than 700 μm. Moreover,
zones could be deliberately positioned in the separation channel
and focusing strength could be precisely tuned employing a three-point
voltage actuation scheme. This makes depletion zone isotachophoresis
(dzITP) a fully controllable single-electrolyte focusing and separation
technique. For on-chip electrokinetic methods, dzITP sets a new standard
in terms of versatility and operational simplicity. },
doi = {10.1021/ac2018348},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac2018348},
url = {http://pubs.acs.org/doi/abs/10.1021/ac2018348}
}
@ARTICLE{Quraishi2011,
author = {Quraishi, Umar Masood and Abrouk, Michael and Murat, Florent and
Pont, Caroline and Foucrier, Séverine and Desmaizieres, Gregory
and Confolent, Carole and Rivière, Nathalie and Charmet, Gilles
and Paux, Etienne and Murigneux, Alain and Guerreiro, Laurent and
Lafarge, Stéphane and Le Gouis, Jacques and Feuillet, Catherine
and Salse, Jerome},
title = {Cross-genome map based dissection of a nitrogen use efficiency ortho-metaQTL
in bread wheat unravels concerted cereal genome evolution},
journal = {The Plant Journal},
year = {2011},
volume = {65},
pages = {745--756},
number = {5},
abstract = {Summary Monitoring nitrogen use efficiency (NUE) in plants is becoming
essential to maintain yield while reducing fertilizer usage. Optimized
NUE application in major crops is essential for long-term sustainability
of agriculture production. Here, we report the precise identification
of 11 major chromosomal regions controlling NUE in wheat that co-localise
with key developmental genes such as Ppd (photoperiod sensitivity),
Vrn (vernalization requirement), Rht (reduced height) and can be
considered as robust markers from a molecular breeding perspective.
Physical mapping, sequencing, annotation and candidate gene validation
of an NUE metaQTL on wheat chromosome 3B allowed us to propose that
a glutamate synthase (GoGAT) gene that is conserved structurally
and functionally at orthologous positions in rice, sorghum and maize
genomes may contribute to NUE in wheat and other cereals. We propose
an evolutionary model for the NUE locus in cereals from a common
ancestral region, involving species specific shuffling events such
as gene deletion, inversion, transposition and the invasion of repetitive
elements.},
doi = {10.1111/j.1365-313X.2010.04461.x},
issn = {1365-313X},
keywords = {cereal synteny, glutamate synthase (GoGAT), ortho-metaQTL, nitrogen
use efficiency},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04461.x}
}
@ARTICLE{Abrahamsson2011,
author = {homas R. Abrahamsson and Hedvig E. Jakobsson and Anders F. Andersson
and Bengt Björkstén and Lars Engstrand and Maria C. Jenmalm},
title = {Low diversity of the gut microbiota in infants with atopic eczema},
journal = {Journal of Allergy and Clinical Immunology},
year = {2011},
volume = {na},
pages = {-},
number = {0},
abstract = {Background It is debated whether a low total diversity of the gut
microbiota in early childhood is more important than an altered prevalence
of particular bacterial species for the increasing incidence of allergic
disease. The advent of powerful, cultivation-free molecular methods
makes it possible to characterize the total microbiome down to the
genus level in large cohorts. Objective We sought to assess microbial
diversity and characterize the dominant bacteria in stool during
the first year of life in relation to atopic eczema development.
Methods Microbial diversity and composition were analyzed with barcoded
16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month,
and 12 months of age in 20 infants with IgE-associated eczema and
20 infants without any allergic manifestation until 2 years of age
(ClinicalTrials.gov ID NCT01285830). Results Infants with IgE-associated
eczema had a lower diversity of the total microbiota at 1 month (PÂ =
.004) and a lower diversity of the bacterial phylum Bacteroidetes
and the genus Bacteroides at 1 month (PÂ = .02 and PÂ = .01) and
the phylum Proteobacteria at 12 months of age (PÂ = .02). The microbiota
was less uniform at 1 month than at 12 months of age, with a high
interindividual variability. At 12 months, when the microbiota had
stabilized, Proteobacteria, comprising gram-negative organisms, were
more abundant in infants without allergic manifestation (Empirical
Analysis of Digital Gene Expression in R [edgeR] test: PÂ = .008,
q = 0.02). Conclusion Low intestinal microbial diversity during
the first month of life was associated with subsequent atopic eczema.},
doi = {10.1016/j.jaci.2011.10.025},
issn = {0091-6749},
keywords = {Allergic disease},
url = {http://www.sciencedirect.com/science/article/pii/S0091674911016575}
}
@BOOK{R.M.2011,
title = {2.53 - Lab on a Chip – Future Technology for Characterizing Biotechnology
Products},
publisher = {Academic Press},
year = {2011},
editor = {Editor-in-Chief:Â Â Murray Moo-Young},
author = {R.M. and Guijt},
pages = {753 - 764},
address = {Burlington},
edition = {Second Edition},
abstract = {Abstract The aim of this article is to provide an overview of lab-on-a-chip
research and to discuss the role that Lab on a Chip technology may
play in the future of analytical chemistry for the characterization
of biotechnology products. With increasing demands from regulatory
organizations to provide quantitative data both for the product and
for the production process of the biotechnological products, the
demand for fast and parallel analysis systems has increased to a
level that existing analytical instrumentation cannot meet demand.
Additionally, research to elucidate biochemical pathways in life
sciences has pushed the current analytical technology to its limits.
Combination of the need for increased throughput and analysis speed
in combination with increasing demands on the resolution indicate
a need for a new generation of analytical tools. Lab-on-a-chip technology
may provide a solution, as it offers fast, parallel, and automated
analysis of minute sample amounts with equivalent or higher resolution
than conventional-scale counterparts. An overview of the technology
and techniques developed for Lab-on-a-chip applications is given.
Microfabrication and fluid manipulation techniques are discussed
together with an overview of methods developed as separate elements
for on-chip analysis. The significance of these developments for
the analysis of biotechnological products is illustrated using three
examples of product assays conducted on currently commercially available
lab on a chip instrumentation.},
booktitle = {Comprehensive Biotechnology (Second Edition)},
doi = {10.1016/B978-0-08-088504-9.00133-1},
isbn = {978-0-08-088504-9},
keywords = {High-throughput analysis},
url = {http://www.sciencedirect.com/science/article/pii/B9780080885049001331}
}
@ARTICLE{Ra2011,
author = {Ra, Seong Hui and Li, Xinmin and Binder, Scott},
title = {Molecular discrimination of cutaneous squamous cell carcinoma from
actinic keratosis and normal skin},
journal = {Mod Pathol},
year = {2011},
pages = {--},
month = apr,
issn = {0893-3952},
publisher = {United States and Canadian Academy of Pathology, Inc.},
url = {http://dx.doi.org/10.1038/modpathol.2011.39}
}
@ARTICLE{Raaben2009,
author = {Raaben, Matthijs and Groot Koerkamp, Marian and Rottier, Peter and
de Haan, Cornelis},
title = {Type I interferon receptor-independent and -dependent host transcriptional
responses to mouse hepatitis coronavirus infection in vivo},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {350},
number = {1},
abstract = {BACKGROUND:The role of type I IFNs in protecting against coronavirus
(CoV) infections is not fully understood. While CoVs are poor inducers
of type I IFNs in tissue culture, several studies have demonstrated
the importance of the type I IFN response in controlling MHV infection
in animals. The protective effectors against MHV infection are, however,
still unknown.RESULTS:In order to get more insight into the antiviral
gene expression induced in the brains of MHV-infected mice, we performed
whole-genome expression profiling. Three different mouse strains,
differing in their susceptibility to infection with MHV, were used.
In BALB/c mice, which display high viral loads but are able to control
the infection, 57 and 121 genes were significantly differentially
expressed (= 1.5 fold change) upon infection at 2 and 5 days post
infection, respectively. Functional association network analyses
demonstrated a strong type I IFN response, with Irf1 and Irf7 as
the central players. At 5 days post infection, a type II IFN response
also becomes apparent. Both the type I and II IFN response, which
were more pronounced in mice with a higher viral load, were not observed
in 129SvEv mice, which are much less susceptible to infection with
MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-),
however, were not able to control the infection. Gene expression
profiling of these mice identified type I IFN-independent responses
to infection, with IFN-? as the central player. As the BALB/c and
the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in
their brains, we also compared their gene expression profiles upon
infection with MHV in order to identify type I IFN-dependent transcriptional
responses. Many known IFN-inducible genes were detected, several
of which have previously been shown to play an important protective
role against virus infections. We speculate that the additional type
I IFN-dependent genes that we discovered may also be important for
protection against MHV infection.CONCLUSION:Transcriptional profiling
of mice infected with MHV demonstrated the induction of a robust
IFN response, which correlated with the viral load. Profiling of
IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent
responses. Overall, this study broadens our present knowledge of
the type I and II IFN-mediated effector responses during CoV infection
in vivo.},
doi = {10.1186/1471-2164-10-350},
issn = {1471-2164},
pubmedid = {19650917},
url = {http://www.biomedcentral.com/1471-2164/10/350}
}
@ARTICLE{Raaben2007,
author = {Raaben, Matthijs and Groot Koerkamp, Marian J. A. and Rottier, Peter
J. M. and De Haan, Cornelis A. M.},
title = {Mouse hepatitis coronavirus replication induces host translational
shutoff and mRNA decay, with concomitant formation of stress granules
and processing bodies},
journal = {Cellular Microbiology},
year = {2007},
volume = {9},
pages = {2218--2229},
number = {9},
abstract = {Summary Many viruses, including coronaviruses, induce host translational
shutoff, while maintaining synthesis of their own gene products.
In this study we performed genome-wide microarray analyses of the
expression patterns of mouse hepatitis coronavirus (MHV)-infected
cells. At the time of MHV-induced host translational shutoff, downregulation
of numerous mRNAs, many of which encode protein translation-related
factors, was observed. This downregulation, which is reminiscent
of a cellular stress response, was dependent on viral replication
and caused by mRNA decay. Concomitantly, phosphorylation of the eukaryotic
translation initiation factor 2α was increased in MHV-infected cells.
In addition, stress granules and processing bodies appeared, which
are sites for mRNA stalling and degradation respectively. We propose
that MHV replication induces host translational shutoff by triggering
an integrated stress response. However, MHV replication per se does
not appear to benefit from the inhibition of host protein synthesis,
at least in vitro, since viral replication was not negatively affected
but rather enhanced in cells with impaired translational shutoff.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2007.00951.x}
}
@ARTICLE{Raaben2008,
author = {Raaben, Matthijs and Whitley, Penn and Bouwmeester, Diane and Setterquist,
Robert and Rottier, Peter and de Haan, Cornelis},
title = {Improved microarray gene expression profiling of virus-infected cells
after removal of viral RNA},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {221},
number = {1},
abstract = {BACKGROUND:Sensitivity and accuracy are key points when using microarrays
to detect alterations in gene expression under different conditions.
Critical to the acquisition of reliable results is the preparation
of the RNA. In the field of virology, when analyzing the host cell's
reaction to infection, the often high representation of viral RNA
(vRNA) within total RNA preparations from infected cells is likely
to interfere with microarray analysis. Yet, this effect has not been
investigated despite the many reports that describe gene expression
profiling of virus-infected cells using microarrays.RESULTS:In this
study we used coronaviruses as a model to show that vRNA indeed interferes
with microarray analysis, decreasing both sensitivity and accuracy.
We also demonstrate that the removal of vRNA from total RNA samples,
by means of virus-specific oligonucleotide capturing, significantly
reduced the number of false-positive hits and increased the sensitivity
of the method as tested on different array platforms.CONCLUSION:We
therefore recommend the specific removal of vRNA, or of any other
abundant 'contaminating' RNAs, from total RNA samples to improve
the quality and reliability of microarray analyses.},
doi = {10.1186/1471-2164-9-221},
issn = {1471-2164},
pubmedid = {18479515},
url = {http://www.biomedcentral.com/1471-2164/9/221}
}
@ARTICLE{Raafat2011,
author = {Raafat, Ahmed and Goldhar, Anita S. and Klauzinska, Malgorzata and
Xu, Keli and Amirjazil, Idean and McCurdy, David and Lashin, Karim
and Salomon, David and Vonderhaar, Barbara K. and Egan, Sean and
Callahan, Robert},
title = {Expression of Notch receptors, ligands, and target genes during development
of the mouse mammary gland},
journal = {Journal of Cellular Physiology},
year = {2011},
volume = {226},
pages = {1940--1952},
number = {7},
abstract = {Abstract Notch genes play a critical role in mammary gland growth,
development and tumorigenesis. In the present study, we have quantitatively
determined the levels and mRNA expression patterns of the Notch receptor
genes, their ligands and target genes in the postnatal mouse mammary
gland. The steady state levels of Notch3 mRNA are the highest among
receptor genes, Jagged1 and Dll3 mRNA levels are the highest among
ligand genes and Hey2 mRNA levels are highest among expressed Hes/Hey
target genes analyzed during different stages of postnatal mammary
gland development. Using an immunohistochemical approach with antibodies
specific for each Notch receptor, we show that Notch proteins are
temporally regulated in mammary epithelial cells during normal mammary
gland development in the FVB/N mouse. The loss of ovarian hormones
is associated with changes in the levels of Notch receptor mRNAs
(Notch2 higher and Notch3 lower) and ligand mRNAs (Dll1 and Dll4
are higher, whereas Dll3 and Jagged1 are lower) in the mammary gland
of ovariectomized mice compared to intact mice. These data define
expression of the Notch ligand/receptor system throughout development
of the mouse mammary gland and help set the stage for genetic analysis
of Notch in this context. J. Cell. Physiol. 226: ??–??, 2011. ©
2010 Wiley-Liss, Inc.},
doi = {10.1002/jcp.22526},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22526}
}
@ARTICLE{Rabani2011,
author = {Rabani, Michal and Levin, Joshua Z and Fan, Lin and Adiconis, Xian
and Raychowdhury, Raktima and Garber, Manuel and Gnirke, Andreas
and Nusbaum, Chad and Hacohen, Nir and Friedman, Nir and Amit, Ido
and Regev, Aviv},
title = {Metabolic labeling of RNA uncovers principles of RNA production and
degradation dynamics in mammalian cells},
journal = {Nat Biotech},
year = {2011},
volume = {29},
pages = {436--442},
number = {5},
month = may,
comment = {10.1038/nbt.1861},
issn = {1087-0156},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nbt.1861}
}
@ARTICLE{Rabiau2010,
author = {Rabiau, Nadège and Kossaï, Myriam and Braud, Martin and Chalabi,
Nasséra and Satih, Samir and Bignon, Yves-Jean and Bernard-Gallon,
Dominique J.},
title = {Genistein and daidzein act on a panel of genes implicated in cell
cycle and angiogenesis by Polymerase Chain Reaction arrays in human
prostate cancer cell lines},
journal = {Cancer Epidemiol},
year = {2010},
volume = {34},
pages = {200--206},
number = {2},
month = apr,
abstract = {Background: The prostate cancer most frequently affects men. The ethnic
origin and family antecedents of prostate cancer are established
as risk factors. The genetic factors associated with environmental
factors such as the nutrition also play a role in the development
of the cancer. Epidemiological studies showed that the Asian populations
exhibited an incidence of prostate cancer markedly subordinate by
comparison with the Western populations. This would be explained
partially by their important consumption of soy. Both main phytoestrogens
of soy, the genistein and the daidzein, present anti-proliferative
properties. Methods: For that purpose, we used different prostate
cancer cell lines (LNCaP, DU 145, PC-3) and, by flow cytometry, we
determined the concentration of phytoestrogens inducing a cell cycle
arrest and the required time of incubation. Results: Then, the effects
of 40μM genistein or 110μM daidzein for 48h were determined and
studied on the expression of genes involved in the human cell cycle
and angiogenesis and conducted by SYBR green quantitative PCR. Conclusion:
We demonstrated modulations of cyclin-dependent kinase-related pathway
genes, DNA damage-signaling pathway and a down-regulation of EGF
and IGF.},
issn = {1877-7821},
keywords = {Prostate cancer cell lines, Daidzein, Genistein, SYBR green, Cell
cycle arrays, Angiogenesis arrays},
publisher = {Elsevier},
refid = {S1877-7821(10)00003-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1877782110000032?showall=true}
}
@ARTICLE{RABIAU2011,
author = {RABIAU, NADEGE and TRRAF, HIBATULLAHI-KAUTHAR and ADJAKLY, MAWUSSI
and BOSVIEL, REMY and GUY, LAURENT and FONTANA, LUC and BIGNON, YVES-JEAN
and BERNARD-GALLON, DOMINIQUE J.},
title = {miRNAs Differentially Expressed in Prostate Cancer Cell Lines after
Soy Treatment},
journal = {In Vivo},
year = {2011},
volume = {25},
pages = {917-921},
number = {6},
abstract = {Background: MicroRNAs (miRNAs) are small non-coding RNAs that have
aberrant expression in prostate cancer tissues. miRNAs are involved
in the initiation and progression of cancer, and several miRNAs have
been characterized as tumor suppressors or oncogenes. It has been
shown that some miRNAs can be directly regulated from their own promoters
by epigenetic alterations in cancer cells. Moreover, phytoestrogens
are known to have epigenetic action on gene transcription. Hence,
we conducted here an examination of the miRNA expression profile
in human prostate cancer cell lines after soy phytoestrogen treatment.
Materials and Methods: The comparative miRNA expression profiles
of prostate cell lines (PC-3, DU145, LNCaP) after a 48-h treatment
of 40 M genistein, 110 M daidzein, or 2 M 5-azacytidine (5-AZA, a
demethylating agent) were conducted with a Taqman low-density array.
Results: We found that out of 377 miRNAs tested, 180, 170 and 150
miRNAs were amplified with 2% of variation in the triplicate in PC-3,
DU145 and LNCap cells, respectively, and only 5 miRNAs for PC-3 and
DU145 cells and 4 miRNAs for LNCap exhibited a significant change
in their expression. Treatment with genistein or daidzein had similar
effects on miRNA regulation to those of 5-AZA treatment. Conclusion:
This work demonstrated a new role of isoflavones on the regulation
of miRNAs in prostate cancer.},
eprint = {http://iv.iiarjournals.org/cgi/reprint/25/6/917.pdf},
url = {http://iv.iiarjournals.org/cgi/content/abstract/25/6/917}
}
@ARTICLE{Rabien2007,
author = {Rabien, Anja and Burkhardt, Mick and Jung, Monika and Fritzsche,
Florian and Ringsdorf, Martin and Schicktanz, Hanka and Loening,
Stefan A. and Kristiansen, Glen and Jung, Klaus},
title = {Decreased RECK Expression Indicating Proteolytic Imbalance in Prostate
Cancer is Associated with Higher Tumor Aggressiveness and Risk of
Prostate-Specific Antigen Relapse after Radical Prostatectomy},
journal = {European Urology},
year = {2007},
volume = {51},
pages = {1259--1266},
number = {5},
month = may,
abstract = {Objectives Decreased expression of reversion-inducing cysteine-rich
protein with Kazal motifs (RECK) was recently shown in several cancer
types. To evaluate its potential role for prostate carcinoma, we
investigated RECK expression in prostate cancer (pCA) samples.Methods
RECK messenger RNA levels in 15 microdissected normal/tumor matches
were determined by quantitative reverse transcriptase-polymerase
chain reaction. Protein expression of RECK was evaluated by immunohistochemical
staining in tissue samples of adenomectomies (n = 24) and pCA samples
after radical prostatectomy (n = 247). RECK expression was related
to preoperative prostate-specific antigen (PSA), tumor stage and
grade, surgical margin status, and PSA relapse-free time after radical
prostatectomy.Results Consistent with lower RECK messenger RNA by
24%, RECK protein expression was decreased in pCA, compared with
adjacent normal tissue and prostatic intraepithelial neoplasia. RECK
expression in samples of benign prostatic hyperplasia from adenomectomy
specimens was higher than in normal adjacent tissue of prostate carcinomas.
Decreased RECK expression was associated with higher Gleason score
(>=7) and higher tumor stage. Multivariate analysis using the Cox
proportional hazards model revealed that negative RECK expression
was an independent prognostic factor for an increased risk of PSA
relapse, especially in patients with higher tumor grades (Gleason
score >=7).Conclusions Decreased RECK expression correlating with
the aggressiveness of pCA and the PSA relapse-free time could become
an adjunct tissue biomarker to improve the follow-up and treatment
decision for these pCA patients.},
issn = {0302-2838},
keywords = {RECK, Prostate cancer, Prognostic marker, Real-time quantitative PCR,
Immunohistochemistry},
url = {http://www.sciencedirect.com/science/article/B6X10-4K605KG-4/2/bda67cb53d10fe7f9817b63eae08fc00}
}
@ARTICLE{Rabinovich2007,
author = {Rabinovich, R. A. and Bastos, R. and Ardite, E. and Llinas, L. and
Orozco-Levi, M. and Gea, J. and Vilaro, J. and Barbera, J. A. and
Rodriguez-Roisin, R. and Fernandez-Checa, J. C. and Roca, J.},
title = {Mitochondrial dysfunction in COPD patients with low body mass index},
journal = {Eur. Respir. J.},
year = {2007},
volume = {29},
pages = {643--650},
number = {4},
month = apr,
abstract = {Patients with chronic obstructive pulmonary disease (COPD) show abnormal
adaptations of skeletal muscle redox status after exercise training.
Increased skeletal muscle oxidative stress in COPD patients may prompt
mitochondrial dysfunction. The present study explores the association
between body composition and mitochondrial respiration in seven COPD
patients with low body mass index (BMIL), eight COPD patients with
normal body mass index (BMIN) and seven healthy controls. All of
them underwent a vastus lateralis biopsy in which muscle structure,
in vitro mitochondrial respiratory function, uncoupling protein 3
(UCP3) mRNA expression and glutathione levels in both isolated mitochondria
and the whole muscle were determined. Mitochondrial respiratory function
(assessed by acceptor control ratio (ACR)) was impaired in BMIL (2.2{+/-}0.6)
compared with both BMIN (5.3{+/-}1.3) and controls (8.2{+/-}1.3).
ACR significantly correlated with arterial oxygen tension and with
muscle endurance but it showed a negative association with exercise-induced
increase in blood lactate levels. UCP3 mRNA expression was reduced
in BMIL patients. In conclusion, chronic obstructive pulmonary disease
patients with low body mass index show electron transport chain dysfunction,
which may contribute to low muscle endurance in the current subgroup
of patients.},
url = {http://erj.ersjournals.com/cgi/content/abstract/29/4/643}
}
@ARTICLE{Rabot2010,
author = {Rabot, Sylvie and Membrez, Mathieu and Bruneau, Aurelia and Gerard,
Philippe and Harach, Taoufiq and Moser, Mireille and Raymond, Frederic
and Mansourian, Robert and Chou, Chieh J.},
title = {Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin
resistance and have altered cholesterol metabolism},
journal = {FASEB J},
year = {2010},
pages = {fj.10-164921--},
month = aug,
abstract = {Recent studies showed that germ-free (GF) mice are resistant to obesity
when consuming a high-fat, high-carbohydrate Western diet. However,
it remains unclear what mechanisms are involved in the antiobesity
phenotype and whether GF mice develop insulin resistance and dyslipidemia
with high-fat (HF) feeding. In the present study, we compared the
metabolic consequences of HF feeding on GF and conventional (conv)
C57BL/6J mice. GF mice consumed fewer calories, excreted more fecal
lipids, and weighed significantly less than conv mice. GF/HF animals
also showed enhanced insulin sensitivity with improved glucose tolerance,
reduced fasting and nonfasting insulinemia, and increased phospho-Akt(Ser-473)
in adipose tissue. In association with enhanced insulin sensitivity,
GF/HF mice had reduced plasma TNF-{alpha} and total serum amyloid
A concentrations. Reduced hypercholesterolemia, a moderate accretion
of hepatic cholesterol, and an increase in fecal cholesterol excretion
suggest an altered cholesterol metabolism in GF/HF mice. Pronounced
nucleus SREBP2 proteins and up-regulation of cholesterol biosynthesis
genes indicate that enhanced cholesterol biosynthesis contributed
to the cholesterol homeostasis in GF/HF mice. Our results demonstrate
that fewer calorie consumption and increased lipid excretion contributed
to the obesity-resistant phenotype of GF/HF mice and reveal that
insulin sensitivity and cholesterol metabolism are metabolic targets
influenced by the gut microbiota.--Rabot, S., Membrez, M., Bruneau,
A., Gerard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R.,
Chou. C. J. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced
insulin resistance and have altered cholesterol metabolism.},
url = {http://www.fasebj.org/cgi/content/abstract/fj.10-164921v1}
}
@ARTICLE{Rachidi2007,
author = {Rachidi, Walid and Harfourche, Ghida and Lemaitre, Gilles and Amiot,
Franck and Vaigot, Pierre and Martin, Michèle T.},
title = {Sensing radiosensitivity of human epidermal stem cells},
journal = {Radiotherapy and Oncology},
year = {2007},
volume = {83},
pages = {267--276},
number = {3},
month = jun,
abstract = {Purpose Radiosensitivity of stem cells is a matter of debate. For
mouse somatic stem cells, both radiosensitive and radioresistant
stem cells have been described. By contrast, the response of human
stem cells to radiation has been poorly studied. As epidermis is
a radiosensitive tissue, we evaluated in the present work the radiosensitivity
of cell populations enriched for epithelial stem cells of human epidermis.Methods
and materials The total keratinocyte population was enzymatically
isolated from normal human skin. We used flow cytometry and antibodies
against cell surface markers to isolate basal cell populations from
human foreskin. Cell survival was measured after a dose of 2 Gy with
the XTT assay at 72 h after exposure and with a clonogenic assay
at 2 weeks. Transcriptome analysis using oligonucleotide microarrays
was performed to assess the genomic cell responses to radiation.Results
Cell sorting based on two membrane proteins, [alpha]6 integrin and
the transferrin receptor CD71, allowed isolation of keratinocyte
populations enriched for the two types of cells found in the basal
layer of epidermis: stem cells and progenitors. Both the XTT assay
and the clonogenic assay showed that the stem cells were radioresistant
whereas the progenitors were radiosensitive. We made the hypothesis
that upstream DNA damage signalling might be different in the stem
cells and used microarray technology to test this hypothesis. The
stem cells exhibited a much more reduced gene response to a dose
of 2 Gy than the progenitors, as we found that 6% of the spotted
genes were regulated in the stem cells and 20% in the progenitors.
Using Ingenuity Pathway Analysis software, we found that radiation
exposure induced very specific pathways in the stem cells. The most
striking responses were the repression of a network of genes involved
in apoptosis and the induction of a network of cytokines and growth
factors.Conclusion These results show for the first time that keratinocyte
populations enriched for stem cells from human epidermis are radioresistant.
Based on both repressed and induced genes, we found that the major
response of the irradiated stem cell population was the regulation
of genes functionally related to cell death, cell survival and apoptosis.},
booktitle = {Highlights from the 10th International ESTRO-Wolfsberg Meeting on
Molecular Radiation Biology/Oncology 2007},
issn = {0167-8140},
keywords = {Keratinocyte, Stem cells, Progenitors, Human epidermis, Radiosensitivity,
Ionizing radiation, Transcriptome, Microarrays},
url = {http://www.sciencedirect.com/science/article/B6TBY-4NVK1NB-1/2/ec9f8083662ae958c62fd1222a8dabb8}
}
@ARTICLE{Rachman2006,
author = {Rachman, Helmy and Strong, Michael and Ulrichs, Timo and Grode, Leander
and Schuchhardt, Johannes and Mollenkopf, Hans and Kosmiadi, George
A. and Eisenberg, David and Kaufmann, Stefan H. E.},
title = {Unique Transcriptome Signature of Mycobacterium tuberculosis in Pulmonary
Tuberculosis},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {1233--1242},
number = {2},
month = feb,
abstract = {Although tuberculosis remains a substantial global threat, the mechanisms
that enable mycobacterial persistence and replication within the
human host are ill defined. This study represents the first genome-wide
expression analysis of Mycobacterium tuberculosis from clinical lung
samples, which has enabled the identification of M. tuberculosis
genes actively expressed during pulmonary tuberculosis. To obtain
optimal information from our DNA array analyses, we analyzed the
differentially expressed genes within the context of computationally
inferred protein networks. Protein networks were constructed using
functional linkages established by the Rosetta stone, phylogenetic
profile, conserved gene neighbor, and operon computational methods.
This combined approach revealed that during pulmonary tuberculosis,
M. tuberculosis actively transcribes a number of genes involved in
active fortification and evasion from host defense systems. These
genes may provide targets for novel intervention strategies.},
url = {http://iai.asm.org/cgi/content/abstract/74/2/1233}
}
@ARTICLE{Rachon2007,
author = {Rachon, Dominik and Vortherms, Tina and Seidlova-Wuttke, Dana and
Wuttke, Wolfgang},
title = {Dietary daidzein and puerarin do not affect pituitary LH expression
but exert uterotropic effects in ovariectomized rats},
journal = {Maturitas},
year = {2007},
volume = {57},
pages = {161--170},
number = {2},
month = jun,
abstract = {Objective: To investigate the potency of LH suppression, as an indirect
measure of alleviation of postmenopausal vasomotor symptoms, as well
as the uterotropic effects of two isoflavones: daidzein and puerarin
in an ovariectomized (ovx) rat model and compare them with the effects
of 17[beta]-estradiol benzoate (E2B). Design: Eighty female Sprague-Dawley
rats were ovx and divided into six different treatment groups and
one control group (11-12 animals per group). Daidzein, puerarin and
E2B were added to the soy free rodent chow in low and high doses
(250 mg and 1000 mg per kg, 600 mg and 3000 mg per kg and 4.3 mg
and 17.3 mg per kg, respectively). After 3 months of treatment, animals
were sacrificed and using real time RT-PCR, pituitary LH[beta] and
uterine IGF-1, PR and C3 mRNA levels were measured. Additionally
serum LH levels were measured in a radioimmunoassay. Results: Both
of our tested isoflavones at low and high doses had no effect on
the expression of the pituitary LH at the mRNA and protein level.
Only E2B at both doses significantly decreased pituitary LH[beta]
gene expression and serum LH levels. Daidzein and puerarin at high
dose increased significantly uterine weights. Uterine IGF-1 gene
expression was only upregulated in puerarin high group. Uterine PR
mRNA levels were higher in animals fed with low dose daidzein and
high dose puerarin. Uterine C3 gene expression was upregulated in
animals fed with daidzein and puerarin at high doses. Although statistically
significant, all these effects were however very discrete compared
to those of E2B at low and high doses. Conclusion: We speculate that
due to the lack of LH suppressing effects in our model, it is very
unlikely for daidzein and puerarin to alleviate vasomotor symptoms
in postmenopausal women. In contrast, due to their uterotropic effects,
high dose consumption of commercially available preparations containing
daidzein or puerarin may expose women with an intact uterus to the
risk of endometrial hyperplasia.},
issn = {0378-5122},
keywords = {Menopause, Phytoestrogens, Daidzein, Puerarin, Pituitary, Uterus},
url = {http://www.sciencedirect.com/science/article/B6T9F-4MX4VV1-1/2/517d91d5f61deba893e211eba529499e}
}
@ARTICLE{Rachon2008,
author = {Rachon, Dominik and Vortherms, Tina and Seidlová-Wuttke, Dana and
Jarry, Hubertus and Wuttke, Wolfgang},
title = {Dietary quercetin does not affect pituitary lutenizing hormone (LH)
expression and has no uterotropic effects in ovariectomized Sprague-Dawley
rats},
journal = {Food and Chemical Toxicology},
year = {2008},
volume = {46},
pages = {513--518},
number = {2},
month = feb,
abstract = {Introduction The aim of this study was to investigate the potency
of LH suppression and the uterotrophic effects of quercetin, a flavonoid
widely present in our diet which in vitro has been shown to posses
estrogenic properties.Methods Fifty-nine female Sprague-Dawley (SD)
rats were ovariectomized (ovx) and fed with soy-free rodent chow
with the addition of quercetin or estradiol-3 benzoate (E2B). Quercetin
was added to the rodent chow at the dose of 200 mg/kg (n = 12) and
1000 mg/kg (n = 11) which on average corresponded to 3.55 mg and
18.42 mg per animal per day, respectively, and E2B at the dose of
4.3 mg/kg (n = 12) or 17.3 mg/kg (n = 12) which corresponded to 0.07 mg
and 0.20 mg per animal per day, respectively. The control group (n = 12)
received soy-free chow only. After three months of treatment, animals
were sacrificed and using real time RT-PCR, pituitary LH[beta] and
uterine insulin like growth factor (IGF)-1, progesterone receptor
(PR) and complement 3 protein (C3) mRNA levels were measured. Additionally,
the in vitro binding capacity of quercetin with a porcine cytosolic
ER preparation was evaluated.Results In contrast to E2B, dietary
quercetin did not decrease pituitary LH expression, had no effects
on uterine weight and uterine expression of estrogen regulated genes.
The binding capacity of quercetin with the ERs was also 35 000-fold
lower compared with 17[beta]-estradiol (E2).Conclusion Our study
shows that quercetin does not show any estrogenic effects in the
pituitary and the uterus of the ovx SD rats.},
issn = {0278-6915},
keywords = {Flavonoids, Quercetin, Pituitary, Uterus, LH, Estrogenic effects},
url = {http://www.sciencedirect.com/science/article/B6T6P-4PJ0523-6/2/55256ca9484789203711ef2fdf5ce632}
}
@ARTICLE{Racz2008,
author = {Racz, Ildiko and Nadal, Xavier and Alferink, Judith and Banos, Josep
E. and Rehnelt, Jennifer and Martin, Miquel and Pintado, Belen and
Gutierrez-Adan, Alfonso and Sanguino, Elena and Bellora, Nicolas
and Manzanares, Jorge and Zimmer, Andreas and Maldonado, Rafael},
title = {Interferon-{gamma} Is a Critical Modulator of CB2 Cannabinoid Receptor
Signaling during Neuropathic Pain},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {12136--12145},
number = {46},
month = nov,
abstract = {Nerve injuries often lead to neuropathic pain syndrome. The mechanisms
contributing to this syndrome involve local inflammatory responses,
activation of glia cells, and changes in the plasticity of neuronal
nociceptive pathways. Cannabinoid CB2 receptors contribute to the
local containment of neuropathic pain by modulating glial activation
in response to nerve injury. Thus, neuropathic pain spreads in mice
lacking CB2 receptors beyond the site of nerve injury. To further
investigate the mechanisms leading to the enhanced manifestation
of neuropathic pain, we have established expression profiles of spinal
cord tissues from wild-type and CB2-deficient mice after nerve injury.
An enhanced interferon-{gamma} (IFN-{gamma}) response was revealed
in the absence of CB2 signaling. Immunofluorescence stainings demonstrated
an IFN-{gamma} production by astrocytes and neurons ispilateral to
the nerve injury in wild-type animals. In contrast, CB2-deficient
mice showed neuronal and astrocytic IFN-{gamma} immunoreactivity
also in the contralateral region, thus matching the pattern of nociceptive
hypersensitivity in these animals. Experiments in BV-2 microglia
cells revealed that transcriptional changes induced by IFN-{gamma}
in two key elements for neuropathic pain development, iNOS (inducible
nitric oxide synthase) and CCR2, are modulated by CB2 receptor signaling.
The most direct support for a functional involvement of IFN-{gamma}
as a mediator of CB2 signaling was obtained with a double knock-out
mouse strain deficient in CB2 receptors and IFN-{gamma}. These animals
no longer show the enhanced manifestations of neuropathic pain observed
in CB2 knock-outs. These data clearly demonstrate that the CB2 receptor-mediated
control of neuropathic pain is IFN-{gamma} dependent.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/46/12136}
}
@ARTICLE{Radeke2007,
author = {Radeke, Monte J. and Peterson, Katie E. and Johnson, Lincoln V. and
Anderson, Don H.},
title = {Disease susceptibility of the human macula: Differential gene transcription
in the retinal pigmented epithelium/choroid},
journal = {Experimental Eye Research},
year = {2007},
volume = {85},
pages = {366--380},
number = {3},
month = sep,
abstract = {The discoveries of gene variants associated with macular diseases
have provided valuable insight into their molecular mechanisms, but
they have not clarified why the macula is particularly vulnerable
to degenerative disease. Its predisposition may be attributable to
specialized structural features and/or functional properties of the
underlying macular RPE/choroid. To examine the molecular basis for
the macula's disease susceptibility, we compared the gene expression
profile of the human RPE/choroid in the macula with the profile in
the extramacular region using DNA microarrays. Seventy-five candidate
genes with differences in macular:extramacular expression levels
were identified by microarray analysis, of which 29 were selected
for further analysis. Quantitative PCR confirmed that 21 showed statistically
significant differences in expression. Five genes were expressed
at higher levels in the macula. Two showed significant changes in
the macular:extramacular expression ratio; another two exhibited
changes in absolute expression level, as a function of age or AMD.
Several of the differentially expressed genes have potential relevance
to AMD pathobiology. One is an RPE cell growth factor (TFPI2), five
are extracellular matrix components (DCN, MYOC, OGN, SMOC2, TFPI2),
and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2)
and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification
of regional differences in gene expression in the RPE/choroid is
a first step in clarifying the macula's propensity for degeneration.
These findings lay the groundwork for further studies into the roles
of the corresponding gene products in the normal, aged, and diseased
macula.},
issn = {0014-4835},
keywords = {macula, retinal pigmented epithelium, choroid, gene expression},
url = {http://www.sciencedirect.com/science/article/B6WFD-4NYSXPM-3/2/79d3d3891ce897ebf1fe4693939d9ca7}
}
@ARTICLE{Rademakers2008,
author = {Rademakers, Rosa and Eriksen, Jason L. and Baker, Matt and Robinson,
Todd and Ahmed, Zeshan and Lincoln, Sarah J. and Finch, Nicole and
Rutherford, Nicola J. and Crook, Richard J. and Josephs, Keith A.
and Boeve, Bradley F. and Knopman, David S. and Petersen, Ronald
C. and Parisi, Joseph E. and Caselli, Richard J. and Wszolek, Zbigniew
K. and Uitti, Ryan J. and Feldman, Howard and Hutton, Michael L.
and Mackenzie, Ian R. and Graff-Radford, Neill R. and Dickson, Dennis
W.},
title = {Common variation in the miR-659 binding-site of GRN is a major risk
factor for TDP43-positive frontotemporal dementia},
journal = {Hum. Mol. Genet.},
year = {2008},
volume = {17},
pages = {3631--3642},
number = {23},
month = dec,
abstract = {Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and
TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia
(FTLD-U), a progressive neurodegenerative disease affecting [~]10%
of early-onset dementia patients. Here we expand the role of GRN
in FTLD-U and demonstrate that a common genetic variant (rs5848),
located in the 3'-untranslated region (UTR) of GRN in a binding-site
for miR-659, is a major susceptibility factor for FTLD-U. In a series
of pathologically confirmed FTLD-U patients without GRN mutations,
we show that carriers homozygous for the T-allele of rs5848 have
a 3.2-fold increased risk to develop FTLD-U compared with homozygous
C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that
miR-659 can regulate GRN expression in vitro, with miR-659 binding
more efficiently to the high risk T-allele of rs5848 resulting in
augmented translational inhibition of GRN. A significant reduction
in GRN protein was observed in homozygous T-allele carriers in vivo,
through biochemical and immunohistochemical methods, mimicking the
effect of heterozygous loss-of-function GRN mutations. In support
of these findings, the neuropathology of homozygous rs5848 T-allele
carriers frequently resembled the pathological FTLD-U subtype of
GRN mutation carriers. We suggest that the expression of GRN is regulated
by miRNAs and that common genetic variability in a miRNA binding-site
can significantly increase the risk for FTLD-U. Translational regulation
by miRNAs may represent a common mechanism underlying complex neurodegenerative
disorders.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/17/23/3631}
}
@ARTICLE{Radeva2010,
author = {Radeva, Mariya and Jahns, Franziska and Wilhelm, Anne and Glei, Michael
and Settmacher, Utz and Greulich, Karl Otto and Mothes, Henning},
title = {Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold
can distinguish between adenoma and fully blown colon carcinoma in
individual patients},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {588},
number = {1},
abstract = {BACKGROUND:It is known that alpha-defensin expression is enhanced
in colon cancer. However, the expression of human alpha defensin
6 (DEFA 6) in earlier stages, such as adenoma, has so far not yet
been studied in a patient resolved manner.METHODS:By using quantitative
Real Time-PCR, the gene expression pattern of DEFA 1-3 and DEFA 6
was analyzed in tissue of different stages of carcinogenesis, derived
from colorectal cancer patients. In addition to paired normal and
tumor tissue, matched normal near tumor and adenoma tissue samples
were examined.RESULTS:The median gene expression of human defensin
alpha 6 (DEFA 6) has been found to be moderately increased (~ 5 fold)
in tumor samples derived from individuals with colorectal cancer
(CRC) when compared to their normal counterparts. However, when the
data were analyzed in a patient-wise manner, a large expression variation
among individual patients is found, making the use of DEFA 6 for
individual diagnosis of fully blown colon carcinoma difficult. Surprisingly,
in adenoma the gene expression analysis revealed a 100 fold increased
median expression of DEFA 6 relative to normal colon tissue. 13/18
samples had an individual overexpression of more than 60 fold in
adenoma but only 3/17 in carcinoma. In each of the individual patients,
at least either the adenoma or the carcinoma showed strong DEFA 6
overexpression.CONCLUSIONS:We suggest that the expression of DEFA
6 preferably can be used as a potential diagnostic marker for adenoma
and not as a marker for fully blown carcinoma. This is supported
by the fact that DEFA 6 is a downstream target of the Wnt pathway,
which is mutational active during the earliest stage of cancer development.},
doi = {10.1186/1471-2407-10-588},
issn = {1471-2407},
pubmedid = {20979654},
url = {http://www.biomedcentral.com/1471-2407/10/588}
}
@ARTICLE{Radke2012,
author = {Lars Radke and Diana A. López Hemmerling and Annika Lubitz and Christoph
Giese and Marcus Frohme},
title = {Induced cytokine response of human PMBC-cultures: Correlation of
gene expression and secretion profiling and the effect of cryopreservation},
journal = {Cellular Immunology},
year = {2012},
volume = {272},
pages = {144 - 153},
number = {2},
abstract = {The immune system is regulated by the complex interaction of multiple
cytokines, which are secreted signaling molecules affecting other
cells. In this work, we studied the cytokine response to several
well-known stimulants, such as OKT-3, Con A, PWM, and SEB. Healthy
donor cells (PBMCs) were cultivated for up to 72 h and the mRNA
levels and cytokine release of four key cytokines (IL-2, IL-4, IFN-γ,
and TNF-α) were analyzed by RT-PCR and bead-based multiplex analyses.
The generated cytokine profiles showed characteristic expression
patterns and secretion kinetics for each cytokine and substance.
PWM/SEB and OKT-3 led to a very fast and long-lasting immune response,
whereas Con A induced the slowest cytokine production. Cytokine concentrations
also differed greatly. The highest IFN-γ concentration was 1000 times
higher than the respective IL-4 concentration. Gene expression and
cytokine concentration profiles were strongly correlated during the
time course.
The chronological response of the donors’ cytokine profiles coincided,
but showed individual characteristics regarding the strength of the
cytokine release.
The comparison of stimulation experiments using freshly isolated and
cryopreserved PBMCs showed that, for the observation of an immunological
response at early points in time, gene expression experiments are
more reliable than the measurement of cytokines in the cell culture
supernatant. However, the freezing of cells influences the response
significantly. The measurement of secreted proteins is the superior
method at later points in time.},
doi = {10.1016/j.cellimm.2011.10.018},
issn = {0008-8749},
keywords = {PBMC stimulation},
url = {http://www.sciencedirect.com/science/article/pii/S0008874911002796}
}
@ARTICLE{Radniecki2008,
author = {Radniecki, T.S. and Ely, R.L.},
title = {Zinc chloride inhibition of Nitrosococcus mobilis},
journal = {Biotechnol. Bioeng.},
year = {2008},
volume = {99},
pages = {1085--1095},
number = {5},
abstract = {Abstract 10.1002/bit.21672.abs Nitrosococcus mobilis, a halophilic
nitrifier, plays an important role in global nitrogen cycling and
in the removal of nitrogen from wastewater treatment plants. However,
ammonia oxidation is sensitive to a wide variety of inhibitors, including
the heavy metal, zinc. Using a metabolic-steady-state reactor, shotgun
DNA microarrays, and quantitative polymerase chain reaction (qPCR),
this research looked at the dynamic physiological and transcriptional
responses of N. mobilis to 1 and 10 µM ZnCl2. By oxygen uptake rate
measurements, zinc was determined to act directly on the ammonia
monooxygenase (AMO) enzyme. The addition of excess copper prevented
the inhibition of AMO by ZnCl2 suggesting that zinc and copper compete
for placement in the metal active site in AMO. Shotgun DNA microarrays
identified four previously unsequenced genes that were up- or down-regulated
in response to 10 µM ZnCl2. Genes up-regulated in response to zinc
inhibition include methionine synthase I, UbiA prenyltransferase
and a recG-like helicase. RuBisCO was the lone down-regulated gene
identified. qPCR was used to track the gene expression of the identified
genes over the course of the 4-h experiment for both ZnCl2 concentrations.
Because of their physiological importance, the expressions of AMO
and hydroxylamine oxidoreductase (HAO) were also monitored via qPCR.
The qPCR results showed general agreement with the shotgun DNA microarray
results for metH, UbiA, recG and RuBisCO, and revealed that AMO and
HAO expression levels were maintained or modestly up-regulated during
ZnCl2 inhibition. Biotechnol. Bioeng. 2008;99: 1085–1095. © 2007
Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {ammonia-oxidizing bacteria, shotgun DNA microarrays, qPCR, stress
response, heavy metal toxicity, nitrification inhibition},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.21672}
}
@ARTICLE{Radniecki2011,
author = {Radniecki, Tyler S. and Lauchnor, Ellen G.},
title = {Investigating Nitrosomonas europaea Stress Biomarkers in Batch, Continuous
Culture, and Biofilm Reactors},
journal = {Methods Enzymol},
year = {2011},
volume = {Volume 496},
pages = {217--246},
abstract = {The understanding of nitrification inhibition in ammonia oxidizing
bacteria (AOB) by priority pollutants and emerging contaminants is
critical in managing the nitrogen cycle to preserve current water
supplies, one of the National Academy of Engineers Grand Challenges
in Engineering for the twenty-first century. Nitrosomonas europaea
is an excellent model AOB for nitrification inhibition experimentation
due to its well-defined NH3 metabolism and the availability of a
wide range of physiological and transcriptional tools that can characterize
the mechanism of nitrification inhibition and probe N. europaea's
response to the inhibitor. This chapter is a compilation of the physiological
and transcriptional methods that have been used to characterize nitrification
inhibition of N. europaea under a wide variety of growth conditions
including batch, continuously cultured, and in biofilms. The protocols
presented here can be applied to other AOB, and may be readily adapted
for other autotrophic bacteria (e.g., nitrite oxidizing bacteria).},
booktitle = {Research on Nitrification and Related Processes, Part B},
editor = {Klotz, Martin G. and Stein, Lisa Y.},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/pii/B9780123864895000099}
}
@BOOK{Radniecki2011a,
title = {Chapter Nine - Investigating Nitrosomonas europaea Stress Biomarkers
in Batch, Continuous Culture, and Biofilm Reactors},
publisher = {Academic Press},
year = {2011},
editor = {Martin G. Klotz and Lisa Y. Stein},
author = {Tyler S. Radniecki and Ellen G. Lauchnor},
volume = {496},
pages = {217 - 246},
series = {Methods in Enzymology},
abstract = {Abstract The understanding of nitrification inhibition in ammonia
oxidizing bacteria (AOB) by priority pollutants and emerging contaminants
is critical in managing the nitrogen cycle to preserve current water
supplies, one of the National Academy of Engineers Grand Challenges
in Engineering for the twenty-first century. Nitrosomonas europaea
is an excellent model AOB for nitrification inhibition experimentation
due to its well-defined NH3 metabolism and the availability of a
wide range of physiological and transcriptional tools that can characterize
the mechanism of nitrification inhibition and probe N. europaea's
response to the inhibitor. This chapter is a compilation of the physiological
and transcriptional methods that have been used to characterize nitrification
inhibition of N. europaea under a wide variety of growth conditions
including batch, continuously cultured, and in biofilms. The protocols
presented here can be applied to other AOB, and may be readily adapted
for other autotrophic bacteria (e.g., nitrite oxidizing bacteria).},
booktitle = {Research on Nitrification and Related Processes, Part B},
doi = {10.1016/B978-0-12-386489-5.00009-9},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/pii/B9780123864895000099}
}
@ARTICLE{Radom-Aizik2009,
author = {Radom-Aizik, Shlomit and Zaldivar, Frank, Jr. and Leu, Szu-Yun and
Cooper, Dan M.},
title = {A brief bout of exercise alters gene expression and distinct gene
pathways in peripheral blood mononuclear cells of early- and late-pubertal
females},
journal = {J Appl Physiol},
year = {2009},
volume = {107},
pages = {168--175},
number = {1},
month = jul,
abstract = {Recent studies show that brief exercise alters circulating neutrophil
and peripheral blood mononuclear cell (PBMC) gene expression, ranging
from cell growth to both pro-and anti-inflammatory processes. These
initial observations were made solely in males, but whether PBMC
gene expression is altered by exercise in females is not known. Ten
early-pubertal girls (8-11 yr old) and 10 late-pubertal girls (15-17
yr old) performed ten 2-min bouts of cycle ergometry ([~]90% peak
heart rate) interspersed with 1-min rest intervals. Blood was obtained
at rest and after exercise, and microarrays were performed in each
individual subject. RNA was hybridized to Affymetrix U133+2.0 Arrays.
Exercise induced significant changes in PBMC gene expression in early
(1,320 genes)- and late (877 genes)-pubertal girls. The expression
of 622 genes changed similarly in both groups. Exercise influenced
a variety of established gene pathways (EASE < 0.04) in both older
(6 pathways) and younger girls (11 pathways). Five pathways were
the same in both groups and were functionally related to inflammation,
stress, and apoptosis, such as natural killer cell-mediated cytotoxicity,
antigen processing and presentation, B cell receptor signaling, and
apoptosis. In summary, brief exercise alters PBMC gene expression
in early- and late-pubertal girls. The pattern of change involves
diverse genetic pathways, consistent with a global danger-type response,
perhaps readying PBMCs for a range of physiological functions from
inflammation to tissue repair that would be useful following a bout
of physical activity.},
url = {http://jap.physiology.org/cgi/content/abstract/107/1/168}
}
@ARTICLE{Radom-Aizik2008,
author = {Radom-Aizik, Shlomit and Zaldivar, Frank, Jr. and Leu, Szu-Yun and
Galassetti, Pietro and Cooper, Dan M.},
title = {Effects of 30 min of aerobic exercise on gene expression in human
neutrophils},
journal = {J Appl Physiol},
year = {2008},
volume = {104},
pages = {236--243},
number = {1},
month = jan,
abstract = {Relatively brief bouts of exercise alter gene expression in peripheral
blood mononuclear cells (PBMCs), but whether exercise changes gene
expression in circulating neutrophils (whose numbers, like PBMCs,
increase) is not known. We hypothesized that exercise would activate
neutrophil genes involved in apoptosis, inflammation, and cell growth
and repair, since these functions in leukocytes are known to be influenced
by exercise. Blood was sampled before and immediately after 30 min
of constant, heavy ([~]80% peak O2 uptake) cycle ergometer exercise
in 12 healthy men (19-29 yr old) of average fitness. Neutrophils
were isolated using density gradients; RNA was hybridized to Affymetrix
U133+2 Genechip arrays. With false discovery rate (FDR) <0.05 with
95% confidence, a total of 526 genes were differentially expressed
between before and after exercise. Three hundred and sixteen genes
had higher expression after exercise. The Jak/STAT pathway, known
to inhibit apoptosis, was significantly activated (EASE score, P
< 0.005), but 14 genes were altered in a way likely to accelerate
apoptosis as well. Similarly, both proinflammatory (e.g., IL-32,
TNFSF8, and CCR5) and anti-inflammatory (e.g., ANXA1) were affected.
Growth and repair genes like AREG and FGF2 receptor genes (involved
in angiogenesis) were also activated. Finally, a number of neutrophil
genes known to be involved in pathological conditions like asthma
and arthritis were altered by exercise, suggesting novel links between
physical activity and disease or its prevention. In summary, brief
heavy exercise leads to a previously unknown substantial and significant
alteration in neutrophil gene expression.},
url = {http://jap.physiology.org/cgi/content/abstract/104/1/236}
}
@ARTICLE{Radom-Aizik2010,
author = {Radom-Aizik, Shlomit and Zaldivar, Frank, Jr. and Oliver, Stacy and
Galassetti, Pietro and Cooper, Dan M.},
title = {Evidence for microRNA involvement in exercise-associated neutrophil
gene expression changes},
journal = {J Appl Physiol},
year = {2010},
volume = {109},
pages = {252--261},
number = {1},
month = jul,
abstract = {Exercise leads to a rapid change in the profile of gene expression
in circulating neutrophils. MicroRNAs (miRNAs) have been discovered
to play important roles in immune function and often act to attenuate
or silence gene translation. We hypothesized that miRNA expression
in circulating neutrophils would be affected by brief exercise. Eleven
healthy men (19-30 yr old) performed 10, 2-min bouts of cycle ergometer
exercise interspersed with 1-min rest at a constant work equivalent
to [~]76% of maximal oxygen uptake ([IMG]f1.gif" ALT="V" BORDER="0">O2max).
We used the Agilent Human miRNA V2 Microarray. A conservative statistical
approach was used to determine that exercise significantly altered
38 miRNAs (20 had lower expression). Using RT-PCR, we verified the
expression level changes from before to after exercise of seven miRNAs.
In silico analysis showed that collectively 36 miRNAs potentially
targeted 4,724 genes (2 of the miRNAs had no apparent gene targets).
Moreover, when we compared the gene expression changes (n = 458)
in neutrophils that have been altered by exercise, as previously
reported, with the miRNAs altered by exercise, we identified three
pathways, Ubiquitin-mediated proteolysis, Jak-STAT signaling pathway,
and Hedgehog signaling pathway, in which an interaction of miRNA
and gene expression was plausible. Each of these pathways is known
to play a role in key mechanisms of inflammation. Brief exercise
alters miRNA profile in circulating neutrophils in humans. These
data support the hypothesis that exercise-associated changes in neutrophil
miRNA expression play a role in neutrophil gene expression in response
to physical activity.},
url = {http://jap.physiology.org/cgi/content/abstract/109/1/252}
}
@ARTICLE{Radpour2009,
author = {Radpour, Ramin and Sikora, Michal and Grussenmeyer, Thomas and Kohler,
Corina and Barekati, Zeinab and Holzgreve, Wolfgang and Lefkovits,
Ivan and Zhong, Xiao Yan},
title = {Simultaneous Isolation of DNA, RNA, and Proteins for Genetic, Epigenetic,
Transcriptomic, and Proteomic Analysis},
journal = {Journal of Proteome Research},
year = {2009},
volume = {8},
pages = {5264-5274},
number = {11},
note = {PMID: 19780627},
doi = {10.1021/pr900591w},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr900591w},
url = {http://pubs.acs.org/doi/abs/10.1021/pr900591w}
}
@ARTICLE{Radtke2012,
author = {Andreas Radtke and Torkjel Bruheim and Jan Egil Afset and KÃ¥re Bergh},
title = {Multiple-locus variant-repeat assay (MLVA) is a useful tool for molecular
epidemiologic analysis of Streptococcus agalactiae strains causing
bovine mastitis},
journal = {Veterinary Microbiology},
year = {2012},
pages = { - },
number = {0},
abstract = {Group B streptococci (GBS) were considered a major cause of mastitis
in cattle until preventive measures succeeded in controlling the
disease in the 1970s and 1980s. During the last 5-6 years an increasing
number of cases have been observed in some Scandinavian countries.
A total of 187 GBS isolates from mastitis cases were collected from
119 animals in 34 Norwegian farms in the period from April 2007 to
November 2010. 133 (71%) of the isolates were from farms with automated
milking systems. The strains underwent typing of capsular polysaccharides
(CPS) and surface proteins, and were analyzed by Multi-Locus Variable
repeat Assay (MLVA) to investigate the epidemiological relationship
of strains within and between farms. The GBS strains were differentiated
into 12 types by CPS and surface protein analysis, with CPS types
V (54%) and IV (34%) predominating. MLVA was superior to CPS and
protein typing for strain differentiation, resolving the 187 strains
into 37 types. In 29 of 34 farms all GBS strains had identical MLVA
profiles specific for each farm. However, in one farm represented
with 48 isolates, four MLVA variants with differences in one repeat
locus were observed during the almost three year long collection
period. Similar variations were observed at four other farms. This
might reflect the stability of repeat loci under in vivo conditions.
Farms with automated milking systems were overrepresented in this
material. In conclusion, the five-loci MLVA allowed rapid high-resolution
genotyping of the bovine GBS strains within and between farms.245
words},
doi = {10.1016/j.vetmic.2011.12.034},
issn = {0378-1135},
keywords = {Mastitis, Bovines, Group B streptococci, Streptococcus agalactiae,
multiple-locus variant number of tandem repeats assay, MLVA},
url = {http://www.sciencedirect.com/science/article/pii/S0378113512000028?v=s5}
}
@ARTICLE{Radtke2010,
author = {Radtke, Andreas and Lindstedt, Bjorn-Arne and Afset, Jan Egil and
Bergh, Kare},
title = {Rapid Multiple-Locus Variant-Repeat Assay (MLVA) for Genotyping of
Streptococcus agalactiae},
journal = {J. Clin. Microbiol.},
year = {2010},
volume = {48},
pages = {2502--2508},
number = {7},
month = jul,
abstract = {Several methods have been used for typing of Streptococcus agalactiae
(group B streptococci [GBS]). Methods currently in use may provide
inadequate resolution (e.g., typing of capsular polysaccharides and
surface protein) or are labor-intensive and expensive (e.g., multilocus
sequence typing [MLST] or pulsed-field gel electrophoresis). This
work describes the construction and use of a multiple-locus variant-repeat
assay (MLVA) on 126 well-characterized human GBS strains, consisting
mostly of invasive Norwegian strains and international reference
strains. Based on in silico whole-genomic analysis of the genomes
of strains A909, NEM316, and 2603V/R, 18 candidate loci were selected
and investigated by PCR. Eleven loci showed diversity, and the five
most diverse loci were used for the construction of an MLVA, consisting
of a multiplex PCR followed by fragment analysis with capillary electrophoresis.
The assay generated clusters which corresponded well with those observed
by other methods. However, it provided a considerably higher degree
of diversity, with 70 different MLVA types compared to 36 types generated
by MLST. Simpson's index of diversity for the 5-locus MLVA was 0.963,
compared to 0.899 for the MLST in this strain collection. MLVA results
will generally be available within 2 days, which is usually faster
than MLST. In our hands, MLVA of GBS represents a rapid, easy, and
comparably inexpensive method for high-resolution genotyping of GBS.},
url = {http://jcm.asm.org/cgi/content/abstract/48/7/2502}
}
@ARTICLE{Rae2006,
author = {Rae, James M. and Johnson, Michael D. and Cordero, Kevin E. and Scheys,
Joshua O. and Larios, José M. and Gottardis, Marco M. and Pienta,
Kenneth J. and Lippman, Marc E.},
title = {GREB1 is a novel androgen-regulated gene required for prostate cancer
growth},
journal = {Prostate},
year = {2006},
volume = {66},
pages = {886--894},
number = {8},
abstract = {Abstract 10.1002/pros.20403.abs BACKGROUND Gene regulated in breast
cancer 1 (GREB1) is a novel estrogen-regulated gene shown to play
a pivotal role in hormone-stimulated breast cancer growth. GREB1
is expressed in the prostate and its putative promoter contains potential
androgen receptor (AR) response elements. METHODS We investigated
the effects of androgens on GREB1 expression and its role in androgen-dependent
prostate cancer growth. RESULTS Real-time PCR demonstrated high level
GREB1 expression in benign prostatic hypertrophy (BPH), localized
prostate cancer (L-PCa), and hormone refractory prostate cancer (HR-PCa).
Androgen treatment of AR-positive prostate cancer cells induced dose-dependent
GREB1 expression, which was blocked by anti-androgens. AR binding
to the GREB1 promoter was confirmed by chromatin immunoprecipitation
(ChIP) assays. Suppression of GREB1 by RNA interference blocked androgen-stimulated
LNCaP cell proliferation. CONCLUSIONS GREB1 is expressed in proliferating
prostatic tissue and prostate cancer, is regulated by androgens,
and suppression of GREB1 blocks androgen-induced growth suggesting
GREB1 may be critically involved in prostate cancer proliferation.
Prostate © 2006 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {prostate cancer, androgen receptor, androgen-induced growth, GREB1},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20403}
}
@ARTICLE{Rae2009,
author = {Rae, Mick and Mohamad, Amirah and Price, Deborah and Hadoke, Patrick
W. F. and Walker, Brian R. and Mason, J. Ian and Hillier, Stephen
G. and Critchley, Hilary O. D.},
title = {Cortisol Inactivation by 11{beta}-Hydroxysteroid dehydrogenase-2
May Enhance Endometrial Angiogenesis via Reduced Thrombospondin-1
in Heavy Menstruation},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {1443--1450},
number = {4},
month = apr,
abstract = {Context: Heavy menstrual bleeding (HMB; menorrhagia) impairs quality
of life for women and requires medication or surgery. Because glucocorticoids
inhibit angiogenesis in other organs, we hypothesized that endometrium
of women with HMB is subject to decreased local glucocorticoid exposure
and enhanced angiogenesis, thereby increasing menstrual bleeding.
Design: Endometrium was collected from 29 women with menstrual complaints.
Menstrual blood loss was measured by alkaline-hematin assay (n =
12, > 80 ml (HMB); n = 17, < 80 ml). Quantitative RT-PCR for thrombospondin-1
(TSP-1) and glucocorticoid-metabolizing enzymes, 11{beta}-hydroxysteroid
dehydrogenases-1 and -2 (11{beta}HSD1,2) was performed. Glucocorticoid
effects on endometrial stromal cells and uterine endothelial cells
(UECs) were determined. RNA interference studies in UECs examined
the effect of TSP-1 ablation on cortisol action. Results: Secretory
phase endometrium mRNA levels for the cortisol inactivating enzyme
11{beta}HSD2 were higher [3.78 {+/-} 1.29 vs. 1.40 {+/-} 0.6 (arbitrary
units), P < 0.05], whereas TSP-1 mRNA was lower [0.40 {+/-} 0.13
vs. 1.66 {+/-} 1.02 (arbitrary units), P < 0.05] in women with HMB.
In cultured endometrial stromal cells and UECs, cortisol increased
TSP-1 expression. Both cortisol and TSP-1 inhibited new vessel formation
in endometrial explants embedded in Matrigel. In UECs cortisol inhibition
of tube-like structure formation was blocked by small interfering
RNA (siRNA) against TSP-1 (25 {+/-} 2.5% cortisol inhibition with
scrambled siRNA vs. 0% cortisol inhibition with TSP-1 siRNA inactivation,
P<0.01). Conclusions: Enhanced inactivation of cortisol by 11{beta}HSD2
in endometrium from women with HMB may explain reduced TSP-1 levels
and hence endothelial cell dysfunction and abnormal angiogenesis.
Inhibition of 11{beta}HSD2 may be a rational novel therapy for heavy
menstrual bleeding.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/4/1443}
}
@ARTICLE{Rae2007,
author = {Rae, M. T. and Gubbay, O. and Kostogiannou, A. and Price, D. and
Critchley, H. O. D. and Hillier, S. G.},
title = {Thyroid Hormone Signaling in Human Ovarian Surface Epithelial Cells},
journal = {J. Clin. Endocrinol. Metab.},
year = {2007},
volume = {92},
pages = {322--327},
number = {1},
month = jan,
abstract = {Context: Ovarian surface epithelial (OSE) cells express multiple nuclear
hormone receptor genes, including those encoding thyroid hormone
and estrogen receptors (TR and ER, respectively). Ovarian cancer
is hormone-dependent, and epidemiological evidence links hyperthyroidism,
inflammation of the ovarian surface, and increased risk of ovarian
cancer. Objective: The objective of this study was to assess T3 action
on human OSE cells in vitro, asking 1) is there evidence for (pre)receptor
control, 2) is T3 inflammatory, and 3) does T3 affect ER expression?
Design: Immunohistochemical analysis of fixed human ovaries and in
vitro analysis of human OSE primary cell cultures were performed.
Patients: Twelve women aged 29-50 yr (median, 41 yr) undergoing elective
gynecological surgery for nonmalignant conditions were studied. Results:
Messenger RNA transcripts for TR{alpha}1, TR{alpha}2, TR{beta}1,
and T3 activating deiodinase 2 and inactivating deiodinase 3 were
present in primary OSE cell cultures by RT-PCR. TR{alpha} and TR{beta}
proteins were also localized to intact OSE by immunohistochemistry.
Treatment of OSE cell cultures for 24 h with T3 caused dose-dependent
mRNA expression of inflammation-associated genes: cyclooxygenase-2,
matrix metalloproteinase-9, and 11{beta}hydroxysteroid dehydrogenase
type 1, determined by quantitative RT-PCR. Finally, treatment with
T3 dose dependently stimulated ER{alpha} mRNA expression without
affecting ER{beta}1 or ER{beta}2. Conclusion: The ovarian surface
is a potential T3 target. T3 exerts direct inflammatory effects on
OSE cell function in vitro. OSE cell responses to T3 include increased
expression of ER{alpha} mRNA, which encodes the ER isoform most strongly
associated with ovarian cancer. This could help explain suggested
epidemiological links between hyperthyroidism and ovarian cancer.},
url = {http://jcem.endojournals.org/cgi/content/abstract/92/1/322}
}
@ARTICLE{Rae2004,
author = {Rae, Michael T. and Niven, Deborah and Critchley, Hilary O. D. and
Harlow, Christopher R. and Hillier, Stephen G.},
title = {Antiinflammatory Steroid Action in Human Ovarian Surface Epithelial
Cells},
journal = {J. Clin. Endocrinol. Metab.},
year = {2004},
volume = {89},
pages = {4538--4544},
number = {9},
month = sep,
abstract = {The human ovarian surface epithelium (OSE) is subject to serial injury
and repair during ovulation, which is a natural inflammatory event.
We asked whether there is a compensatory antiinflammatory component
to this process, involving steroid hormones produced locally at the
time of ovulation. Quantitative RT-PCR analysis of total RNA from
cultured human OSE cell monolayers showed that exposure to proinflammatory
IL1{alpha} (500 pg/ml) increased mRNA levels of cyclooxygenase-2
(COX-2) (P < 0.01) at 48 h. The COX-2 mRNA response to IL1{alpha}
was associated with an approximate 18-fold (P < 0.01) increase in
mRNA levels of 11{beta}-hydroxysteroid dehydrogenase type 1 (11{beta}HSD1),
encoding the steroid dehydrogenase that reversibly reduces cortisone
to antiinflammatory cortisol. Addition of cortisol to OSE cell culture
medium dose-dependently suppressed the COX-2 mRNA response to IL1{alpha}
(P < 0.01) but reciprocally enhanced the 11{beta}HSD1 mRNA response
(P < 0.05), with both effects strongest at 1 {micro}M cortisol. Presence
of glucocorticoid receptor-{alpha} mRNA and protein was established
in OSE cell monolayers and treatment with IL1{alpha} shown to significantly
up-regulate the glucocorticoid receptor-{alpha} mRNA level (P < 0.05).
Glucocorticoid receptor antagonist (RU486, 10 {micro}M) fully reversed
the inhibitory effect of 1 {micro}M cortisol on IL1{alpha}-stimulated
COX-2 mRNA expression. Progesterone also suppressed IL1{alpha}-induced
COX-2 mRNA expression but had no significant effect on IL1{alpha}-stimulated
11{beta}HSD1 expression. These data provide direct evidence for antiinflammatory
actions of cortisol and progesterone in human OSE cells.},
url = {http://jcem.endojournals.org/cgi/content/abstract/89/9/4538}
}
@ARTICLE{Rae2004a,
author = {Rae, M T and Niven, D and Ross, A and Forster, T and Lathe, R and
Critchley, H O D and Ghazal, P and Hillier, S G},
title = {Steroid signalling in human ovarian surface epithelial cells: the
response to interleukin-1{alpha} determined by microarray analysis},
journal = {J. Endocrinol.},
year = {2004},
volume = {183},
pages = {19--28},
number = {1},
month = oct,
abstract = {The human ovarian surface epithelium (HOSE) is a common site of gynaecological
disease including endometriosis and ovarian cancer, probably due
to serial injury-repair events associated with successive ovulations.
To comprehend the importance of steroid signalling in the regulation
of the HOSE, we used a custom microarray to catalogue the expression
of over 250 genes involved in the synthesis and reception of steroid
hormones, sterols and retinoids. The array included a subset of non-steroidogenic
genes commonly involved in pro-/anti-inflammatory signalling. HOSE
cells donated by five patients undergoing surgery for non-malignant
gynaecological conditions were cultured for 48 h in the presence
and absence of 500 pg/ ml interleukin-1{alpha} (IL-1{alpha}). Total
RNA was reverse-transcribed into biotin-labelled cDNA, which was
hybridised to the array and visualised by gold-particle resonance
light scattering and charge-coupled device (CCD) camera detection.
Results for selected genes were verified by quantitative reverse-transcription
PCR. In five out of five cases, untreated HOSE cells expressed genes
encoding enzymes required for de novo biosynthesis of cholesterol
from acetate and subsequent formation of C21-pregnane and C19-androstane
steroids. Consistent with the inability of HOSE cells to synthesise
glucocorticoids, oestrogens or 5{alpha}-reduced androgens de novo,
CYP21, CYP19 and 5{alpha}-reductase were not detected. The only steroidogenic
gene significantly up-regulated by IL-1{alpha} was 11{beta}-hydroxysteroid
dehydrogenase type 1 (11{beta}HSD1). Other cytokine-induced genes
were IL-6, IL-8, nuclear factor {kappa}B (NF{kappa}B) inhibitor {alpha},
metallothionein-IIA and lysyl oxidase: inflammation-associated genes
that respond to glucocorticoids. The only steroidogenic gene significantly
suppressed by IL-1{alpha} was 3{beta}HSD1. Other genes suppressed
by IL-1{alpha} were aldehyde dehydrogenase (ALDH) 1, ALDH 10, gonadotrophin
hormone-releasing hormone receptor, peroxisome proliferation-activated
receptor-binding protein (PPAR-bp) and nuclear receptor subfamily
2 group F member 2. These results define a steroidogenic phenotype
of cultured HOSE cells and provide a limited expression profile for
genes with associated signalling functions. IL-1{alpha} co-ordinately
induces 11{beta}HSD1 and a panel of glucocorticoid-regulated, inflammation-associated
genes in HOSE cells, providing further evidence that cortisol generated
by 11{beta}HSD1 could participate in the local resolution of inflammation
associated with ovulation.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/183/1/19}
}
@ARTICLE{Rae2009a,
author = {Rae, Michael T. and Price, Deborah and Harlow, Christopher R. and
Critchley, Hilary O.D. and Hillier, Stephen G.},
title = {Glucocorticoid receptor-mediated regulation of MMP9 gene expression
in human ovarian surface epithelial cells},
journal = {Fertility and Sterility},
year = {2009},
volume = {92},
pages = {703--708},
number = {2},
month = aug,
issn = {0015-0282},
keywords = {Ovarian surface epithelium, inflammation, ovulation, steroids, extracellular
matrix, ovarian cancer},
url = {http://www.sciencedirect.com/science/article/B6T6K-4T8H3F5-5/2/f2b9ef3395af658685919f1fa525ea43}
}
@ARTICLE{Raetz2006,
author = {Raetz, Elizabeth A. and Perkins, Sherrie L. and Bhojwani, Deepa and
Smock, Kristi and Philip, Mary and Carroll, William L. and Min, Dong-Joon},
title = {Gene expression profiling reveals intrinsic differences between T-cell
acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma},
journal = {Pediatr. Blood Cancer},
year = {2006},
volume = {47},
pages = {130--140},
number = {2},
abstract = {Abstract 10.1002/pbc.20550.abs Background T-cell acute lymphoblastic
leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are
often thought to represent a spectrum of a single disease. The malignant
cells in T-ALL and T-LL are morphologically indistinguishable, and
they share the expression of common cell surface antigens and cytogenetic
characteristics. However, despite these similarities, differences
in the clinical behavior of T-ALL and T-LL are observed. Procedure
We analyzed the gene expression profiles of T-ALL and T-LL samples
obtained from Children's Oncology Group (COG) tumor banks using DNA
arrays. Immunohistochemistry was also performed to validate the expression
of selected targets. Results Unsupervised hierarchical clustering
of all samples showed complete segregation of T-ALL and T-LL into
distinct clusters. Next, we identified the top 201 genes that best
differentiated T-ALL from T-LL using significance analysis of microarrays
(SAM), a supervised statistical approach. Genes representing several
functional groups were differentially expressed in T-LL and T-ALL.
Prediction analysis of microarrays (PAM) identified a subset of genes,
which accurately classified all 19 T-ALL and T-LL samples with an
overall misclassification error rate of 0. Immunohistochemical validation
of protein expression of selected genes identified by microarray
analysis confirmed overexpression of MLL-1 in T-LL tumor cells compared
to T-ALL and CD47 in T-ALL tumors cells when compared to T-LL. Conclusions
Despite significant similarities between the malignant T-cell precursors,
clear differences in the gene expression profiles were observed between
T-ALL and T-LL implying underlying differences in the biology of
the two entities. Pediatr Blood Cancer © 2005 Wiley-Liss, Inc.},
issn = {1545-5017},
keywords = {gene expression profiling, lymphoblastic lymphoma, T-cell ALL},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pbc.20550}
}
@ARTICLE{Rafael2007,
author = {Rafael, A.I. and Almeida, A. and Santos, P. and Parreira, I. and
Madeira, V.M.S. and Alves, R. and Cabrita, A.M.S. and Alpoim, M.C.},
title = {A role for transforming growth factor-[beta] apoptotic signaling
pathway in liver injury induced by ingestion of water contaminated
with high levels of Cr(VI)},
journal = {Toxicology and Applied Pharmacology},
year = {2007},
volume = {224},
pages = {163--173},
number = {2},
month = oct,
abstract = {Hexavalent chromium [Cr(VI)] exposure is commonly associated with
lung cancer. Although other adverse health effects have been reported,
some authors, on assuming that orally ingested Cr(VI) is efficiently
detoxified upon reduction by body fluids, believe that Cr(VI) do
not target cells other than respiratory tract cells. In rodents,
ingested Cr(VI)-contaminated water was reported to induce, in the
liver, increases in TGF-[beta] transcripts. As TGF-[beta] dependent
signaling pathways are closely associated with hepatic injury, the
present study was undertaken addressing two specific issues: the
effects of ingestion of water contaminated with high levels of Cr(VI)
in rat liver structure and function; and the role of the TGF-[beta]
pathway in Cr(VI)-induced liver injury. Examination of Wistar rats
exposed to 20 ppm Cr(VI)-contaminated water for 10 weeks showed increased
serum glucose and alanine aminotransferase (ALT) levels. Liver histological
examination revealed hepatocellular apoptosis, further confirmed
by immunohystochemical study of Caspase 3 expression. Liver gene
expression analysis revealed increased expression of Smad2/Smad4
and Dapk, suggesting the involvement of the TGF-[beta] pathway in
the apoptotic process. Since no changes in Smad3 expression were
observed it appears apoptosis is using a Smad3-independent pathway.
Increased expression of both Caspase 8 and Daxx genes suggests also
the involvement of the Fas pathway. Gene expression analysis also
revealed that a p160ROCK-Rho-independent pathway operates, leading
to cell contraction and membrane blebbing, characteristic apoptotic
features. These findings suggest that either the amount of Cr(VI)
ingested overwhelmed the body fluids reductive capacity or some Cr(VI)
escapes the reductive protection barrier, thus targeting the liver
and inducing apoptosis.},
issn = {0041-008X},
keywords = {Hexavalent chromium, Drinking water, Liver injury, Apoptosis, TGF-[beta]
pathway},
url = {http://www.sciencedirect.com/science/article/B6WXH-4P718JK-1/2/afaa422b391664f5a1e2cdf8120e1ee2}
}
@ARTICLE{Raffaello2006,
author = {Raffaello, Anna and Laveder, Paolo and Romualdi, Chiara and Bean,
Camilla and Toniolo, Luana and Germinario, Elena and Megighian, Aram
and Danieli-Betto, Daniela and Reggiani, Carlo and Lanfranchi, Gerolamo},
title = {Denervation in murine fast-twitch muscle: short-term physiological
changes and temporal expression profiling},
journal = {Physiol Genomics},
year = {2006},
volume = {25},
pages = {60--74},
number = {1},
month = mar,
abstract = {Denervation deeply affects muscle structure and function, the alterations
being different in slow and fast muscles. Because the effects of
denervation on fast muscles are still controversial, and high-throughput
studies on gene expression in denervated muscles are lacking, we
studied gene expression during atrophy progression following denervation
in mouse tibialis anterior (TA). The sciatic nerve was cut close
to trochanter in adult CD1 mice. One, three, seven, and fourteen
days after denervation, animals were killed and TA muscles were dissected
out and utilized for physiological experiments and gene expression
studies. Target cDNAs from TA muscles were hybridized on a dedicated
cDNA microarray of muscle genes. Seventy-one genes were found differentially
expressed. Microarray results were validated, and the expression
of relevant genes not probed on our array was monitored by real-time
quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes
implicated in energy metabolism were consistently downregulated.
Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic
reticulum), genes typical of fast fibers were downregulated, whereas
those typical of slow fibers were upregulated. Electrophoresis and
Western blot showed less pronounced changes in myofibrillar protein
expression, partially confirming changes in gene expression. Isometric
tension of skinned fibers was little affected by denervation, whereas
calcium sensitivity decreased. Functional studies in mouse extensor
digitorum longus muscle showed prolongation in twitch time parameters
and shift to the left in force-frequency curves after denervation.
We conclude that, if studied at the mRNA level, fast muscles appear
not less responsive than slow muscles to the interruption of neural
stimulation.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/25/1/60}
}
@ARTICLE{Raffaello2010,
author = {Raffaello, Anna and Milan, Giulia and Masiero, Eva and Carnio, Silvia
and Lee, Donghoon and Lanfranchi, Gerolamo and Goldberg, Alfred Lewis
and Sandri, Marco},
title = {JunB transcription factor maintains skeletal muscle mass and promotes
hypertrophy},
journal = {J. Cell Biol.},
year = {2010},
volume = {191},
pages = {101--113},
number = {1},
month = oct,
abstract = {The size of skeletal muscle cells is precisely regulated by intracellular
signaling networks that determine the balance between overall rates
of protein synthesis and degradation. Myofiber growth and protein
synthesis are stimulated by the IGF-1/Akt/mammalian target of rapamycin
(mTOR) pathway. In this study, we show that the transcription factor
JunB is also a major determinant of whether adult muscles grow or
atrophy. We found that in atrophying myotubes, JunB is excluded from
the nucleus and that decreasing JunB expression by RNA interference
in adult muscles causes atrophy. Furthermore, JunB overexpression
induces hypertrophy without affecting satellite cell proliferation
and stimulated protein synthesis independently of the Akt/mTOR pathway.
When JunB is transfected into denervated muscles, fiber atrophy is
prevented. JunB blocks FoxO3 binding to atrogin-1 and MuRF-1 promoters
and thus reduces protein breakdown. Therefore, JunB is important
not only in dividing populations but also in adult muscle, where
it is required for the maintenance of muscle size and can induce
rapid hypertrophy and block atrophy.},
url = {http://jcb.rupress.org/cgi/content/abstract/191/1/101}
}
@ARTICLE{Rafferty2011,
author = {Rafferty, B. and Jönsson, D. and Kalachikov, S. and Demmer, R. T.
and Nowygrod, R. and Elkind, M. S. V. and Bush, H. and Kozarov, E.},
title = {Impact of monocytic cells on recovery of uncultivable bacteria from
atherosclerotic lesions},
journal = {Journal of Internal Medicine},
year = {2011},
volume = {270},
pages = {273--280},
number = {3},
abstract = {Abstract.  Rafferty B, Jönsson D, Kalachikov S, Demmer RT, Nowygrod
R, Elkind MSV, Bush Jr H, Kozarov E. (Columbia University Medical
Center, New York, NY; and Weill Cornell Medical College, New York,
NY; USA) Impact of monocytic cells on recovery of uncultivable bacteria
from atherosclerotic lesions. J Intern Med 2011; 270: 273–280.Objective. 
Epidemiological evidence suggests that infections may contribute
to atherogenesis. However, with the exception of Chlamydophila pneumoniae,
cultivable bacteria have not been recovered from atherosclerotic
lesions. Therefore, we aimed at developing an approach to recover
uncultivable bacteria from atherectomy tissues.Methods.  We cultured
homogenates from atherectomy specimens from seven nonseptic patients
undergoing surgery for arterial obstruction either alone or together
with THP-1 monocyte-like cells. We performed 16S rDNA analysis, biochemical
tests, random amplification of polymorphic DNA PCR analysis, quantitative
polymerase chain reaction (qPCR) and immunohistofluorescence to identify
the cultivated bacteria. Wilcoxon signed-rank tests were used to
determine whether THP-1 treatment yielded a higher number of isolates
than did the untreated controls.Results.  We recovered more bacteria
from cocultures of atherectomy specimens with THP-1 cells than atherectomy
specimens cultured alone. On average, tissue homogenates incubated
with THP-1 cells versus control yielded 124 vs. 22 colony-forming
units, a median of 140 vs. 7, respectively (PÂ =Â 0.02). We recovered
872 isolates of limited number of species, including Propionibacterium
acnes, Staphylococcus epidermidis and Streptococcus infantis and
the fastidious anaerobe Porphyromonas gingivalis, and confirmed its
presence in tissue using double immunofluorescence imaging. qPCR
demonstrated the presence of ≥3.5 × 103P. gingivalis genomes
per gram of atheromatous tissue.Conclusions.  These results indicate
that viable previously uncultivable bacterial species are present
within atheromas. Our results suggest revisiting the hypothesis that
infections may have a causative role in atherosclerotic inflammation
and have implications for research regarding novel diagnostics and
treatments for cardiovascular disease.},
doi = {10.1111/j.1365-2796.2011.02373.x},
issn = {1365-2796},
keywords = {atherosclerosis, bacterial infection, monocytes, periodontal disease,
Porphyromonas gingivalis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2796.2011.02373.x}
}
@ARTICLE{RAFFERTY2007,
author = {RAFFERTY, MAIRIN and FALLER, WILLIAM J. and MOSS, CATHERINE and MCCORMACK,
JANET and MALANDSMO, GUNHILD M. and EASTY, DAVID J. and GALLAGHER,
WILLIAM M.},
title = {Real-time Quantitative Reverse Transcriptase-polymerase Chain Reaction
Analysis of Melanoma Progression-associated Genes},
journal = {Anticancer Res},
year = {2007},
volume = {27},
pages = {1301--1307},
number = {3A},
month = may,
abstract = {Background: Melanoma is an aggressive disease that spreads quickly
and is resistant to most therapeutic agents. In an effort to provide
insight into the molecular basis of melanoma progression, the expression
of 94 genes in 20 metastatic melanomas using a high-throughput real-time
quantitative RT-PCR assay was analysed. Materials and Methods: A
TaqMan low density array (LDA) was designed containing probes/primers
directed towards a cohort of genes previously found to be differentially
expressed in an isogenic cell line model of melanoma progression.
For each sample, cDNA was prepared and added to the quantitative
assay. The resulting data were then analysed for correlations with
clinical data. Results: Clustering analysis divided the melanomas
into two major subgroups based on gene expression patterns. When
analysed individually, several genes were associated with overall
survival, depth and type of the primary tumour. Conclusion: We have
identified a selection of genes linked to melanoma progression and
patient outcome.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/27/3A/1301}
}
@ARTICLE{Ragetly2010,
author = {Ragetly, Guillaume and Griffon, Dominique J. and Chung, Yong Sik},
title = {The effect of type II collagen coating of chitosan fibrous scaffolds
on mesenchymal stem cell adhesion and chondrogenesis},
journal = {Acta Biomater},
year = {2010},
volume = {6},
pages = {3988--3997},
number = {10},
month = oct,
abstract = {The biocompatibility of chitosan and its similarity to glycosaminoglycans
(GAG) make it attractive for cartilage tissue engineering. We have
previously reported improved chondrogenesis but limited cell adhesion
on chitosan scaffolds. Our objectives were to produce chitosan scaffolds
coated with different densities of type II collagen and to evaluate
the effect of this coating on mesenchymal stem cell (MSC) adhesion
and chondrogenesis. Chitosan fibrous scaffolds were obtained by a
wet spinning method and coated with type II collagen at two different
densities. A polyglycolic acid mesh served as a reference group.
The scaffolds were characterized by Fourier-transform infrared spectroscopy,
scanning electron microscopy (SEM), transmission electron microscopy
(TEM) and type II collagen content. Constructs were analyzed after
MSCs seeding via live/dead assay, weight and DNA evaluations, SEM,
and TEM. Constructs were cultured in chondrogenic medium for 21 days
prior to quantitative analysis (weight, DNA, and GAG), SEM, TEM,
histology, immunohistochemistry, and quantitative real time polymerase
chain reaction. The cell attachment and distribution after seeding
correlated with the density of type II collagen. The cell number,
the matrix production, and the expression of genes specific for chondrogenesis
were improved after culture in collagen coated chitosan constructs.
These findings encourage the use of type II collagen for coating
chitosan scaffolds to improve MSCs adhesion and chondrogenesis, and
confirm the importance of biomimetic scaffolds for tissue engineering.},
issn = {1742-7061},
keywords = {Chitosan, Type II collagen, Mesenchymal stem cells, Cell adhesion,
Chondrogenesis},
publisher = {Elsevier,},
refid = {S1742-7061(10)00244-8},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1742706110002448?showall=true}
}
@ARTICLE{Raggo2005,
author = {Raggo, Camilo and Ruhl, Rebecca and McAllister, Shane and Koon, Henry
and Dezube, Bruce J. and Fruh, Klaus and Moses, Ashlee V.},
title = {Novel Cellular Genes Essential for Transformation of Endothelial
Cells by Kaposi's Sarcoma-Associated Herpesvirus},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {5084--5095},
number = {12},
month = jun,
abstract = {Kaposi's sarcoma-associated herpesvirus (KSHV) is involved in the
development of lymphoproliferative diseases and Kaposi's sarcoma.
The oncogenicity of this virus is reflected in vitro by its ability
to transform B cells and endothelial cells. Infection of dermal microvascular
endothelial cells (DMVEC) transforms the cells from a cobblestone-like
monolayer to foci-forming spindle cells. This transformation is accompanied
by dramatic changes in the cellular transcriptome. Known oncogenes,
such as c-Kit, are among the KSHV-induced host genes. We previously
showed that c-Kit is an essential cellular component of the KSHV-mediated
transformation of DMVEC. Here, we test the hypothesis that the transformation
process can be used to discover novel oncogenes. When expression
of a panel of KSHV-induced cellular transcripts was inhibited with
antisense oligomers, we observed inhibition of DMVEC proliferation
and foci formation using antisense molecules to RDC1 and Neuritin.
We further showed that transformation of KSHV-infected DMVEC was
inhibited by small interfering RNA directed at RDC1 or Neuritin.
Ectopic expression of Neuritin in NIH 3T3 cells resulted in changes
in cell morphology and anchorage-independent growth, whereas RDC1
ectopic expression significantly increased cell proliferation. In
addition, both RDC1- and Neuritin-expressing cells formed tumors
in nude mice. RDC1 is an orphan G protein-coupled receptor, whereas
Neuritin is a growth-promoting protein known to mediate neurite outgrowth.
Neither gene has been previously implicated in tumorigenesis. Our
data suggest that KSHV-mediated transformation involves exploitation
of the hitherto unrealized oncogenic properties of RDC1 and Neuritin.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/12/5084}
}
@ARTICLE{Raghavachari2007,
author = {Raghavachari, Nalini and Xu, Xiuli and Harris, Amy and Villagra,
Jose and Logun, Carolea and Barb, Jennifer and Solomon, Michael A.
and Suffredini, Anthony F. and Danner, Robert L. and Kato, Gregory
and Munson, Peter J. and Morris, Sidney M., Jr and Gladwin, Mark
T.},
title = {Amplified Expression Profiling of Platelet Transcriptome Reveals
Changes in Arginine Metabolic Pathways in Patients With Sickle Cell
Disease},
journal = {Circulation},
year = {2007},
volume = {115},
pages = {1551--1562},
number = {12},
month = mar,
abstract = {Background-- In sickle cell disease, ischemia-reperfusion injury and
intravascular hemolysis produce endothelial dysfunction and vasculopathy
characterized by reduced nitric oxide and arginine bioavailability.
Recent functional studies of platelets in patients with sickle cell
disease reveal a basally activated state, which suggests that pathological
platelet activation may contribute to sickle cell disease vasculopathy.
Methods and Results-- Studies were therefore undertaken to examine
transcriptional signaling pathways in platelets that may be dysregulated
in sickle cell disease. We demonstrate and validate in the present
study the feasibility of comparative platelet transcriptome studies
on clinical samples from single donors by the application of RNA
amplification followed by microarray-based analysis of 54 000 probe
sets. Data mining an existing microarray database, we identified
220 highly abundant genes in platelets and a subset of 72 relatively
platelet-specific genes, defined by >10-fold increased expression
compared with the median of other cell types in the database with
amplified transcripts. The highly abundant platelet transcripts found
in the present study included 82% or 70% of platelet-abundant genes
identified in 2 previous gene expression studies on nonamplified
mRNA from pooled or apheresis samples, respectively. On comparing
the platelet gene expression profiles in 18 patients with sickle
cell disease in steady state to those of 12 black control subjects,
at a 3-fold cutoff and 5% false-discovery rate, we identified {approx}100
differentially expressed genes, including multiple genes involved
in arginine metabolism and redox homeostasis. Further characterization
of these pathways with real-time polymerase chain reaction and biochemical
assays revealed increased arginase II expression and activity and
decreased platelet polyamine levels. Conclusions-- The present studies
suggest a potential pathogenic role for platelet arginase and altered
arginine and polyamine metabolism in sickle cell disease and provide
a novel framework for the study of disease-specific platelet biology.},
url = {http://circ.ahajournals.org/cgi/content/abstract/115/12/1551}
}
@ARTICLE{Raghavan2011,
author = {Raghavan, Rahul and Groisman, Eduardo A. and Ochman, Howard},
title = {Genome-wide detection of novel regulatory RNAs in E. coli},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1487-1497},
number = {9},
abstract = {The intergenic regions in bacterial genomes can contain regulatory
leader sequences and small RNAs (sRNAs), which both serve to modulate
gene expression. Computational analyses have predicted the presence
of hundreds of these noncoding regulatory RNAs in Escherichia coli;
however, only about 80 have been experimentally validated. By applying
a deep-sequencing approach, we detected and quantified the vast majority
of the previously validated regulatory elements and identified 10
new sRNAs and nine new regulatory leader sequences in the intergenic
regions of E. coli. Half of the newly discovered sRNAs displayed
enhanced stability in the presence of the RNA-binding protein Hfq,
which is vital to the function of many of the known E. coli sRNAs.
Whereas previous methods have often relied on phylogenetic conservation
to identify regulatory leader sequences, only five of the newly discovered
E. coli leader sequences were present in the genomes of other enteric
species. For those newly identified regulatory elements having orthologs
in Salmonella, evolutionary analyses showed that these regions encoded
new noncoding elements rather than small, unannotated protein-coding
transcripts. In addition to discovering new noncoding regulatory
elements, we validated 53 sRNAs that were previously predicted but
never detected and showed that the presence, within intergenic regions,
of {sigma}70 promoters and sequences with compensatory mutations
that maintain stable RNA secondary structures across related species
is a good predictor of novel sRNAs.},
doi = {10.1101/gr.119370.110},
eprint = {http://genome.cshlp.org/cgi/reprint/21/9/1487.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/9/1487}
}
@ARTICLE{Raghuveer2010,
author = {Raghuveer, Kavarthapu and Senthilkumaran, Balasubramanian},
title = {Cloning and differential expression pattern of vasa in the developing
and recrudescing gonads of catfish, Clarias gariepinus},
journal = {Comparative Biochemistry and Physiology - Part A: Molecular \& Integrative
Physiology},
year = {2010},
volume = {157},
pages = {79--85},
number = {1},
month = sep,
abstract = {Vasa gene codes for a DEAD box family protein, which plays a crucial
role in primordial germ cell proliferation. In this study, we report
cloning of vasa from gonads of air-breathing catfish, Clarias gariepinus,
a seasonally reproducing teleost fish. We studied the expression
pattern of vasa during gametogenesis using real-time PCR. We also
examined the hormonal regulation on vasa in gonads of catfish. RT-PCR
analysis revealed that vasa was detectable only in the gonads. Further,
real-time PCR results showed that expression of vasa was seen throughout
the development from embryonic stage to adult. However, the expression
was more in ovary than in testis during gonadal development. In adult
testis, the vasa transcripts were significantly high during spermatogenesis
and it declined during spermiation. On the other hand, during ovarian
recrudescence, vasa transcripts were high in immature oocytes (stages
I and II oocytes) when compared to mature oocytes (stages III and
IV oocytes). Human chorionic gonadotropin treatment in recrudescing
ovary (in vivo) as well as in testicular slices (in vitro) resulted
in up regulation of vasa mRNA in a time-dependant manner. These results
together suggest that vasa gene has got an important role to play
in spermatogenesis and oogenesis during recrudescence in addition
to development.},
issn = {1095-6433},
keywords = {Vasa, Testis, Ovary, Gametogenesis, hCG induction},
url = {http://www.sciencedirect.com/science/article/B6VNH-5025VDS-1/2/6fd68fa0a90b34d6ef93398d78da8241}
}
@ARTICLE{Ragland2011,
author = {Ragland, Gregory J. and Egan, Scott P. and Feder, Jeffrey L. and
Berlocher, Stewart H. and Hahn, Daniel A.},
title = {Developmental trajectories of gene expression reveal candidates for
diapause termination: a key life-history transition in the apple
maggot fly Rhagoletis pomonella},
journal = {J. Exp. Biol.},
year = {2011},
volume = {214},
pages = {3948-3960},
number = {23},
abstract = {The timing of dormancy is a rapidly evolving life-history trait playing
a crucial role in the synchronization of seasonal life cycles and
adaptation to environmental change. But the physiological mechanisms
regulating dormancy in animals remain poorly understood. In insects,
dormancy (diapause) is a developmentally dynamic state, and the mechanisms
that control diapause transitions affect seasonal timing. Here we
used microarrays to examine patterns of gene expression during dormancy
termination: a crucial life-history transition in the apple maggot
fly Rhagoletis pomonella (Walsh). This species is a model system
for host race formation and ecological speciation via changes in
diapause regulation of seasonality. Our goal was to pinpoint the
timing of the transition from diapause to post-diapause development
and to identify candidate genes and pathways for regulation of diapause
termination. Samples were taken at six metabolically defined developmental
landmarks, and time-series analysis suggests that release from metabolic
depression coincides with preparation for or resumption of active
cell cycling and morphogenesis, defining the end' of diapause. However,
marked changes in expression, including members of pathways such
as Wnt and TOR signaling, also occur prior to the metabolic rate
increase, electing these pathways as candidates for early regulation
of diapause termination. We discuss these results with respect to
generalities in insect diapause physiology and to our long-term goal
of identifying mechanisms of diapause adaptation in the Rhagoletis
system.},
doi = {10.1242/jeb.061085},
eprint = {http://jeb.biologists.org/cgi/reprint/214/23/3948.pdf},
url = {http://jeb.biologists.org/cgi/content/abstract/214/23/3948}
}
@ARTICLE{Ragni2011,
author = {Ragni, Enrico and Piberger, Heidi and Neupert, Christine and García-Cantalejo,
Jesús and Popolo, Laura and Arroyo, Javier and Aebi, Markus and Strahl,
Sabine},
title = {The genetic interaction network of CCW12, a Saccharomyces cerevisiae
gene required for cell wall integrity during budding and formation
of mating projections},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {107},
number = {1},
abstract = {BACKGROUND:Mannoproteins construct the outer cover of the fungal cell
wall. The covalently linked cell wall protein Ccw12p is an abundant
mannoprotein. It is considered as crucial structural cell wall component
since in baker's yeast the lack of CCW12 results in severe cell wall
damage and reduced mating efficiency.RESULTS:In order to explore
the function of CCW12, we performed a Synthetic Genetic Analysis
(SGA) and identified genes that are essential in the absence of CCW12.
The resulting interaction network identified 21 genes involved in
cell wall integrity, chitin synthesis, cell polarity, vesicular transport
and endocytosis. Among those are PFD1, WHI3, SRN2, PAC10, FEN1 and
YDR417C, which have not been related to cell wall integrity before.
We correlated our results with genetic interaction networks of genes
involved in glucan and chitin synthesis. A core of genes essential
to maintain cell integrity in response to cell wall stress was identified.
In addition, we performed a large-scale transcriptional analysis
and compared the transcriptional changes observed in mutant ccw12?
with transcriptomes from studies investigating responses to constitutive
or acute cell wall damage. We identified a set of genes that are
highly induced in the majority of the mutants/conditions and are
directly related to the cell wall integrity pathway and cell wall
compensatory responses. Among those are BCK1, CHS3, EDE1, PFD1, SLT2
and SLA1 that were also identified in the SGA. In contrast, a specific
feature of mutant ccw12? is the transcriptional repression of genes
involved in mating. Physiological experiments substantiate this finding.
Further, we demonstrate that Ccw12p is present at the cell periphery
and highly concentrated at the presumptive budding site, around the
bud, at the septum and at the tip of the mating projection.CONCLUSIONS:The
combination of high throughput screenings, phenotypic analyses and
localization studies provides new insight into the function of Ccw12p.
A compensatory response, culminating in cell wall remodelling and
transport/recycling pathways is required to buffer the loss of CCW12.
Moreover, the enrichment of Ccw12p in bud, septum and mating projection
is consistent with a role of Ccw12p in preserving cell wall integrity
at sites of active growth.The microarray data produced in this analysis
have been submitted to NCBI GEO database and GSE22649 record was
assigned.},
doi = {10.1186/1471-2164-12-107},
issn = {1471-2164},
pubmedid = {21320323},
url = {http://www.biomedcentral.com/1471-2164/12/107}
}
@ARTICLE{Raha2010,
author = {Raha, Debasish and Wang, Zhong and Moqtaderi, Zarmik and Wu, Linfeng
and Zhong, Guoneng and Gerstein, Mark and Struhl, Kevin and Snyder,
Michael},
title = {Close association of RNA polymerase II and many transcription factors
with Pol III genes},
journal = {PNAS},
year = {2010},
volume = {107},
pages = {3639--3644},
number = {8},
month = feb,
abstract = {Transcription of the eukaryotic genomes is carried out by three distinct
RNA polymerases I, II, and III, whereby each polymerase is thought
to independently transcribe a distinct set of genes. To investigate
a possible relationship of RNA polymerases II and III, we mapped
their in vivo binding sites throughout the human genome by using
ChIP-Seq in two different cell lines, GM12878 and K562 cells. Pol
III was found to bind near many known genes as well as several previously
unidentified target genes. RNA-Seq studies indicate that a majority
of the bound genes are expressed, although a subset are not suggestive
of stalling by RNA polymerase III. Pol II was found to bind near
many known Pol III genes, including tRNA, U6, HVG, hY, 7SK and previously
unidentified Pol III target genes. Similarly, in vivo binding studies
also reveal that a number of transcription factors normally associated
with Pol II transcription, including c-Fos, c-Jun and c-Myc, also
tightly associate with most Pol III-transcribed genes. Inhibition
of Pol II activity using {alpha}-amanitin reduced expression of a
number of Pol III genes (e.g., U6, hY, HVG), suggesting that Pol
II plays an important role in regulating their transcription. These
results indicate that, contrary to previous expectations, polymerases
can often work with one another to globally coordinate gene expression.},
url = {http://www.pnas.org/cgi/content/abstract/107/8/3639}
}
@ARTICLE{Raheem2010,
author = {Raheem, Olayinka and Olufemi, Shodimu-Emmanuel and Bachinski, Linda
L. and Vihola, Anna and Sirito, Mario and Holmlund-Hampf, Jeanette
and Haapasalo, Hannu and Li, Yi-Ping and Udd, Bjarne and Krahe, Ralf},
title = {Mutant (CCTG)n Expansion Causes Abnormal Expression of Zinc Finger
Protein 9 (ZNF9) in Myotonic Dystrophy Type 2},
journal = {Am. J. Pathol.},
year = {2010},
volume = {177},
pages = {3025--3036},
number = {6},
month = dec,
abstract = {The mutation that underlies myotonic dystrophy type 2 (DM2) is a (CCTG)n
expansion in intron 1 of zinc finger protein 9 (ZNF9). It has been
suggested that ZNF9 is of no consequence for disease pathogenesis.
We determined the expression levels of ZNF9 during muscle cell differentiation
and in DM2 muscle by microarray profiling, real-time RT-PCR, splice
variant analysis, immunofluorescence, and Western blotting. Our results
show that in differentiating myoblasts, ZNF9 protein was localized
primarily to the nucleus, whereas in mature muscle fibers, it was
cytoplasmic and organized in sarcomeric striations at the Z-disk.
In patients with DM2, ZNF9 was abnormally expressed. First, there
was an overall reduction in both the mRNA and protein levels. Second,
the subcellular localization of the ZNF9 protein was somewhat less
cytoplasmic and more membrane-bound. Third, our splice variant analysis
revealed retention of intron 3 in an aberrant isoform, and fourth
quantitative allele-specific expression analysis showed the persistence
of intron 1 sequences from the abnormal allele, further suggesting
that the mutant allele is incompletely spliced. Thus, the decrease
in total expression appears to be due to impaired splicing of the
mutant transcript. Our data indicate that ZNF9 expression in DM2
patients is altered at multiple levels. Although toxic RNA effects
likely explain overlapping phenotypic manifestations between DM1
and DM2, abnormal ZNF9 levels in DM2 may account for the differences
in DM1.},
comment = {10.2353/ajpath.2010.100179},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/6/3025}
}
@ARTICLE{Rahimov2011,
author = {Rahimov, Fedik and King, Oliver D. and Warsing, Leigh C. and Powell,
Rachel E. and Emerson, Charles P., Jr. and Kunkel, Louis M. and Wagner,
Kathryn R.},
title = {Gene expression profiling of skeletal muscles treated with a soluble
activin type IIB receptor},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {398--407},
number = {8},
month = apr,
abstract = {Inhibition of the myostatin signaling pathway is emerging as a promising
therapeutic means to treat muscle wasting and degenerative disorders.
Activin type IIB receptor (ActRIIB) is the putative myostatin receptor,
and a soluble activin receptor (ActRIIB-Fc) has been demonstrated
to potently inhibit a subset of transforming growth factor (TGF)-{beta}
family members including myostatin. To determine reliable and valid
biomarkers for ActRIIB-Fc treatment, we assessed gene expression
profiles for quadriceps muscles from mice treated with ActRIIB-Fc
compared with mice genetically lacking myostatin and control mice.
Expression of 134 genes was significantly altered in mice treated
with ActRIIB-Fc over a 2-wk period relative to control mice (fold
change > 1.5, P < 0.001), whereas the number of significantly altered
genes in mice treated for 2 days was 38, demonstrating a time-dependent
response to ActRIIB-Fc in overall muscle gene expression. The number
of significantly altered genes in Mstn-/- mice relative to control
mice was substantially higher (360), but for most of these genes
the expression levels in the 2-wk treated mice were closer to the
levels in the Mstn-/- mice than in control mice (P < 10-30). Expression
levels of 30 selected genes were further validated with quantitative
real-time polymerase chain reaction (qPCR), and a correlation of
[≥]0.89 was observed between the fold changes from the microarray
analysis and the qPCR analysis. These data suggest that treatment
with ActRIIB-Fc results in overlapping but distinct gene expression
signatures compared with myostatin genetic mutation. Differentially
expressed genes identified in this study can be used as potential
biomarkers for ActRIIB-Fc treatment, which is currently in clinical
trials as a therapeutic agent for muscle wasting and degenerative
disorders.},
comment = {10.1152/physiolgenomics.00223.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/8/398}
}
@ARTICLE{Rahm2006,
author = {Rahm, Brian G. and Morris, Robert M. and Richardson, Ruth E.},
title = {Temporal Expression of Respiratory Genes in an Enrichment Culture
Containing Dehalococcoides ethenogenes},
journal = {Appl. Envir. Microbiol.},
year = {2006},
volume = {72},
pages = {5486--5491},
number = {8},
month = aug,
abstract = {Multiple reductive dehalogenase (RDase), hydrogenase (H2ase), and
other respiration-associated (RA) oxidoreductase genes have been
identified in cultured representatives of Dehalococcoides. Although
their products are likely to play key roles in the environmentally
important process of reductive dechlorination, very little information
is available about their regulation and specific functions. Here
we show increased expression and temporal variability in the expression
of five RDase genes and in the expression of genes for a putative
formate dehydrogenase (Fdh) and two H2ases, including a periplasmic
[Ni/Fe] H2ase (Hup) and a cytoplasmic [Fe] H2ase (Vhu). mRNA transcripts
extracted from tetrachloroethene-dechlorinating mixed cultures corresponding
to Fdh, the H2ase Hup, and the RDase targets TceA and DET0162 were
expressed most highly, with average levels 34 ({+/-} 7.5)-, 23 ({+/-}
6.7)-, 16 ({+/-} 3.3)-, and 13 ({+/-} 3.3)-fold higher, respectively,
than that for RNA polymerase (RpoB). H2ase and RA transcripts reached
their respective expression maxima within the first 2 h after feeding.
RDase transcripts, however, were most highly expressed after 3 h
and exhibited greater temporal variability than other transcripts.
Comparison with D. ethenogenes strain 195 pure culture expression
levels indicated that RDase DET1545 was more highly expressed in
mixed cultures, where, on average, its transcript level was sixfold
higher than that of RpoB. While the specific functions of several
of these gene products remain elusive, the high expression levels
and temporal variability reported here suggest that these groups
of enzymes are metabolically important for the respiration of chlorinated
ethenes in mixed cultures containing Dehalococcoides.},
url = {http://aem.asm.org/cgi/content/abstract/72/8/5486}
}
@ARTICLE{Rahm2008,
author = {Rahm, Brian G. and Richardson, Ruth E.},
title = {Correlation of Respiratory Gene Expression Levels and Pseudo-Steady-State
PCE Respiration Rates in Dehalococcoides ethenogenes},
journal = {Environmental Science \& Technology},
year = {2008},
volume = {42},
pages = {416-421},
number = {2},
note = {PMID: 18284140},
doi = {10.1021/es071455s},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/es071455s},
url = {http://pubs.acs.org/doi/abs/10.1021/es071455s}
}
@ARTICLE{Rahman2011,
author = {Rahman, Mozibur and Inman, Mark and Kiss, Lorand and Janssen, Luke
J.},
title = {Reverse-mode NCX-current in mouse airway smooth muscle: Na+- and
voltage-dependence, contributions to Ca2+-influx and contraction,
and altered expression in a model of allergen-induced hyperresponsiveness},
journal = {Acta Physiologica},
year = {2011},
pages = {n/a--n/a},
abstract = {Aim:We examined the electrophysiological properties of reverse-mode
Na+/Ca2+-exchange (NCX) in mouse airway smooth muscle (ASM), assessing
its contributions to regulation of [Ca2+], and its expression in
acute and chronic airway hyperresponsiveness (AHR).Methods:Membrane
currents were studied in single murine ASM cells under voltage clamp
at -60 mV using ramp depolarizing commands to +80 mV. Confocal fluorimetric
and RT-PCR techniques were used to monitor changes in cytosolic [Ca2+]
and NCX expression, respectively.Results:With standard KCl-containing
electrode, 30 μM KB-R7943 (an inhibitor of reverse-mode NCX activity)
exhibited variable effects on membrane current, indicating modulation
of more than one conductance. KB-R7943 activated outwardly rectifying
current which was inhibited by 100 μM iberiotoxin (blocker of large-conductance
Ca2+-dependent K+ channels), indicating a direct enhancing effect
of KB-R7943 on those K+-channels. After obviating K+ currents, we
found that a current sensitive to DIDS (blocker of Ca2+-dependent
Cl- channels) was markedly increased by elevating [Na+] in the electrode
solution to 13, 15.5 and 18 mM, and suppressed by KB-R7943, indicating
Ca2+-influx via reverse-mode NCX activity. With conditions preventing
Ca2+-influx through voltage-dependent Ca2+ channels but promoting
that through NCX, we found introduction of Ca2+ led to marked but
transient KB-R7943-sensitive elevation of [Ca2+]. Additionally, KB-R7943
suppressed cholinergically-evoked Ca2+-waves. Finally, NCX1 expression
was not significantly changed in allergen-induced AHR acute model,
but increased ~2.5-fold in a chronic model.Conclusion:Reverse-mode
NCX activity leads to a physiologically relevant increase in [Ca2+]
even under control conditions, and this may be exaggerated in allergen-induced
AHR and asthma.},
doi = {10.1111/j.1748-1716.2011.02401.x},
issn = {1748-1716},
keywords = {Airway smooth muscle, reverse mode sodium calcium exchanger, KB-R7943,
airway hyperresponsiveness},
url = {http://dx.doi.org/10.1111/j.1748-1716.2011.02401.x}
}
@ARTICLE{Rainen2002,
author = {Rainen, Lynne and Oelmueller, Uwe and Jurgensen, Stewart and Wyrich,
Ralf and Ballas, Cynthia and Schram, Jim and Herdman, Chris and Bankaitis-Davis,
Danute and Nicholls, Nancy and Trollinger, David and Tryon, Victor},
title = {Stabilization of mRNA Expression in Whole Blood Samples},
journal = {Clin. Chem.},
year = {2002},
volume = {48},
pages = {1883--1890},
number = {11},
month = nov,
abstract = {Background: Accurate quantification of mRNA in whole blood is made
difficult by the simultaneous degradation of gene transcripts and
unintended gene induction caused by sample handling or uncontrolled
activation of coagulation. This study was designed to compare a new
blood collection tube (PAXgeneTM Blood RNA System) and a companion
sample preparation reagent set with a traditional sample collection
and preparation method for the purpose of gene expression analysis.
Methods: We collected parallel blood samples from healthy donors
into the new sample collection tubes and control EDTA tubes and performed
serial RNA extractions on samples stored for 5 days at room temperature
and for up to 90 days at 4 and 20 {degrees}C. Samples were analyzed
by Northern blot analysis or reverse transcription-PCR (RT-PCR).
Results: Specific mRNA concentrations in blood stored in EDTA tubes
at any temperature changed substantially, as determined by high-precision
RT-PCR. These changes were eliminated or markedly reduced when whole
blood was stored in PAXgene tubes. Loss of specific mRNAs, as measured
by RT-PCR, reflected total RNA depletion as well as specific mRNA
destruction demonstrated by Northern blot analysis. The salutary
effects of PAXgene on mRNA stabilization extended to blood samples
from eight unrelated donors. Conclusions: Compared with whole blood
collected in EDTA tubes and extracted by an organic method, the PAXgene
Blood RNA System reduced RNA degradation and inhibited or eliminated
gene induction in phlebotomy whole blood samples. Storage of whole
blood samples in PAXgene tubes can be recommended for clinically
related blood samples that will be analyzed for total or specific
RNA content.},
url = {http://www.clinchem.org/cgi/content/abstract/48/11/1883}
}
@ARTICLE{Rainis2005,
author = {Rainis, Liat and Toki, Tsutomu and Pimanda, John E. and Rosenthal,
Ester and Machol, Keren and Strehl, Sabine and Gottgens, Berthold
and Ito, Etsuro and Izraeli, Shai},
title = {The Proto-Oncogene ERG in Megakaryoblastic Leukemias},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {7596--7602},
number = {17},
month = sep,
abstract = {Aneuploidy is one of the hallmarks of cancer. Acquired additions of
chromosome 21 are a common finding in leukemias, suggesting a contributory
role to leukemogenesis. About 10% of patients with a germ line trisomy
21 (Down syndrome) are born with transient megakaryoblastic leukemia.
We and others have shown acquired mutations in the X chromosome gene
GATA1 in all these cases. The gene or genes on chromosome 21 whose
overexpression promote the megakaryoblastic phenotype are presently
unknown. We propose that ERG, an Ets transcription factor situated
on chromosome 21, is one such candidate. We show that ERG is expressed
in hematopoietic stem cells, megakaryoblastic cell lines, and in
primary leukemic cells from Down syndrome patients. ERG expression
is induced upon megakaryocytic differentiation of the erythroleukemia
cell lines K562 and UT-7, and forced expression of ERG in K562 cells
induces erythroid to megakaryoblastic phenotypic switch. We also
show that ERG activates the gpIb megakaryocytic promoter and binds
the gpIIb promoter in vivo. Furthermore, both ERG and ETS2 bind in
vivo the hematopoietic enhancer of SCL/TAL1, a key regulator of hematopoietic
stem cell and megakaryocytic development. We propose that trisomy
21 facilitates the occurrence of megakaryoblastic leukemias through
a shift toward the megakaryoblastic lineage caused by the excess
expression of ERG, and possibly by other chromosome 21 genes, such
as RUNX1 and ETS2, in hematopoietic progenitor cells, coupled with
a differentiation arrest caused by the acquisition of mutations in
GATA1.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/17/7596}
}
@ARTICLE{Rajadhyaksha2010,
author = {Rajadhyaksha, Anjali M. and Elemento, Olivier and Puffenberger, Erik
G. and Schierberl, Kathryn C. and Xiang, Jenny Z. and Putorti, Maria
L. and Berciano, José and Poulin, Chantal and Brais, Bernard and
Michaelides, Michel and Weleber, Richard G. and Higgins, Joseph J.},
title = {Mutations in FLVCR1 Cause Posterior Column Ataxia and Retinitis Pigmentosa},
journal = {The American Journal of Human Genetics},
year = {2010},
volume = {87},
pages = {643--654},
number = {5},
month = nov,
abstract = {The study of inherited retinal diseases has advanced our knowledge
of the cellular and molecular mechanisms involved in sensory neural
signaling. Dysfunction of two specific sensory modalities, vision
and proprioception, characterizes the phenotype of the rare, autosomal-recessive
disorder posterior column ataxia and retinitis pigmentosa (PCARP).
Using targeted DNA capture and high-throughput sequencing, we analyzed
the entire 4.2 Mb candidate sequence on chromosome 1q32 to find the
gene mutated in PCARP in a single family. Employing comprehensive
bioinformatic analysis and filtering, we identified a single-nucleotide
coding variant in the feline leukemia virus subgroup C cellular receptor
1 (FLVCR1), a gene encoding a heme-transporter protein. Sanger sequencing
confirmed the FLVCR1 mutation in this family and identified different
homozygous missense mutations located within the protein's transmembrane
channel segment in two other unrelated families with PCARP. To determine
whether the selective pathologic features of PCARP correlated with
FLVCR1 expression, we examined wild-type mouse Flvcr1 mRNA levels
in the posterior column of the spinal cord and the retina via quantitative
real-time reverse-transcriptase PCR. The Flvcr1 mRNA levels were
most abundant in the retina, followed by the posterior column of
the spinal cord and other brain regions. These results suggest that
aberrant FLVCR1 causes a selective degeneration of a subpopulation
of neurons in the retina and the posterior columns of the spinal
cord via dysregulation of heme or iron homeostasis. This finding
broadens the molecular basis of sensory neural signaling to include
common mechanisms that involve proprioception and vision.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S000292971000529X}
}
@ARTICLE{Rajagopalan2009,
author = {Rajagopalan, Govindarajan and Tilahun, Ashenafi Y. and Asmann, Yan
W. and David, Chella S.},
title = {Early gene expression changes induced by the bacterial superantigen
staphylococcal enterotoxin B and its modulation by a proteasome inhibitor},
journal = {Physiol Genomics},
year = {2009},
volume = {37},
pages = {279--293},
number = {3},
month = may,
abstract = {Toxic shock syndrome (TSS) is an acute, serious systemic illness caused
by bacterial superantigens. Nonavailability of a suitable animal
model until recently has hampered an in-depth understanding of the
pathogenesis of TSS. In the current study, we characterized the early
molecular events underlying TSS using our HLA-DR3 transgenic mouse
model. Gene expression profiling using DNA microarrays identified
a rapid and significant upregulation of several pro- as well as anti-inflammatory
mediators, many of which have never been previously described in
TSS. In vivo administration of staphylococcal enterotoxin B (SEB)
led to an increase in the expression of Th0- (IL-2, 240-fold); Th1-
(IFN-{gamma}, 360-fold; IL-12, 8-fold); Th2- (IL-4, 53-fold; IL-5,
4-fold) as well as Th17-type cytokines (IL-21, 19-fold; IL-17, 5-fold).
The immunoregulatory cytokines (IL-6, 700-fold; IL-10, 18-fold);
CC chemokines (such as CCL 2, 11, 3, 24, 17, 12, 7), CXC chemokines
(such as CXCL 1, 2, 5, 11, 10, 19); and several proteases (matrix
metalloproteinases 13, 8, 3, and 9) were also upregulated. Serum
levels of several of these cytokines/chemokines were also significantly
elevated. Pathway analyses revealed significant modulation in a variety
of biochemical and cellular functions, providing molecular insights
into the pathogenesis of TSS. Administration of bortezomib, a clinically
approved proteasome inhibitor capable of blocking NF-{kappa}B pathway,
was able to significantly modulate the expression of a variety of
genes induced by SEB. Thus, our study showed that TSS is a complex
process and emphasized the potential of use of bortezomib in the
therapy of superantigen-induced TSS.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/37/3/279}
}
@ARTICLE{Rajan2011,
author = {Rajan, N and Elliott, R and Clewes, O and Mackay, A and Reis-Filho,
J S and Burn, J and Langtry, J and Sieber-Blum, M and Lord, C J and
Ashworth, A},
title = {Dysregulated TRK signalling is a therapeutic target in CYLD defective
tumours},
journal = {Oncogene},
year = {2011},
pages = {--},
month = may,
issn = {1476-5594},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/onc.2011.133}
}
@ARTICLE{Rajan2006,
author = {Rajan, Sudarsan and Williams, Sarah S. and Jagatheesan, Ganapathy
and Ahmed, Rafeeq P. H. and Fuller-Bicer, Geraldine and Schwartz,
Arnold and Aronow, Bruce J. and Wieczorek, David F.},
title = {Microarray analysis of gene expression during early stages of mild
and severe cardiac hypertrophy},
journal = {Physiol Genomics},
year = {2006},
volume = {27},
pages = {309--317},
number = {3},
month = nov,
abstract = {Familial hypertrophic cardiomyopathy (FHC) is a disease characterized
by ventricular hypertrophy, fibrosis, and aberrant systolic and/or
diastolic function. We previously developed two transgenic mouse
models that carry FHC-associated mutations in {alpha}-tropomyosin
(TM): FHC {alpha}-TM175 mice show patchy areas of mild ventricular
disorganization and limited hypertrophy, whereas FHC {alpha}-TM180
mice exhibit severe hypertrophy and fibrosis and die within 6 mo.
To obtain a better understanding of the molecular mechanisms associated
with the early onset of cardiac hypertrophy, we conducted a detailed
comparative analysis of gene expression in 2.5-mo-old control, FHC
{alpha}-TM175, and {alpha}-TM180 ventricular tissue. Results show
that 754 genes (from a total of 22,600) were differentially expressed
between the nontransgenic (NTG) and the FHC hearts. There are 178
differentially regulated genes between NTG and the FHC {alpha}-TM175
hearts, 388 genes are differentially expressed between NTG and FHC
{alpha}-TM180 hearts, and 266 genes are differentially expressed
between FHC {alpha}-TM175 and FHC {alpha}-TM180 hearts. Genes that
exhibit the largest increase in expression belong to the "secreted/extracellular
matrix" category, and those with the most significant decrease in
expression are associated with "metabolic enzymes." Confirmation
of the microarray analysis was conducted by quantitative real-time
PCR on gene transcripts commonly associated with cardiac hypertrophy.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/27/3/309}
}
@ARTICLE{Rajasekaran2008,
author = {Rajasekaran, Namakkal S. and Firpo, Matthew A. and Milash, Brett
A. and Weiss, Robert B. and Benjamin, Ivor J.},
title = {Global expression profiling identifies a novel biosignature for protein
aggregation R120GCryAB cardiomyopathy in mice},
journal = {Physiol Genomics},
year = {2008},
volume = {35},
pages = {165--172},
number = {2},
month = oct,
abstract = {Protein aggregation cardiomyopathy is a life-threatening manifestation
of a multisystem disorder caused by the exchange mutation in the
gene encoding the human small heat shock protein {alpha}B-crystallin
(hR120GCryAB). Genetic studies in mice have established cardiac hR120GCryAB
expression causes increased activity of glucose 6-phosphate dehydrogenase
(G6PD) and "reductive stress" (Rajasekaran et al., Cell 130: 427-439,
2007). However, the initiating molecular events in the pathogenesis
of this novel toxic gain-of-function mechanism remain poorly defined.
In an integrated systems approach using gene expression profiling,
we identified a "biosignature," whose features can be validated to
predict the onset, rate of progression, and clinical outcome of R120GCryAB
cardiomyopathy. At the 3 mo disease-related but compensated stage,
we demonstrate that transcripts were only upregulated in three distinct
pathways: stress response (e.g., Hsp70, Hsp90), glutathione metabolism
(Gpx1, Gpx3, glutathione S-transferase), and complement and coagulation
cascades in hR120GCryAB transgenic mouse hearts compared with either
hCryAB WT transgenic mice or nontransgenic controls. In 6 mo old
myopathic hearts, ribosomal synthesis and cellular remodeling associated
with increased cardiac hypertrophy were additional upregulated pathways.
In contrast, the predominant downregulated pathways were for oxidative
phosphorylation, fatty acid metabolism, intermediate metabolism,
and energetic balance, supporting their primary pathogenic roles
by which G6PD-dependent reductive stress causes cardiac decompensation
and overt heart failure in hR120GCryAB cardiomyopathy. This study
extends and confirms our previous findings that reductive stress
is a causal mechanism for hR120G CryAB cardiomyopathy and demonstrates
that alteration in glutathione pathway gene expression is an early
biosignature with utility for presymptomatic detection.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/35/2/165}
}
@ARTICLE{Rajecki2009,
author = {Rajecki, Maria and Hällström, Taija af and Hakkarainen, Tanja and
Nokisalmi, Petri and Hautaniemi, Sampsa and Nieminen, Anni I. and
Tenhunen, Mikko and Rantanen, Ville and Desmond, Reneé A. and Chen,
Dung-Tsa and Guse, Kilian and Stenman, Ulf-HÃ¥kan and Gargini, Ricardo
and Kapanen, Mika and Klefström, Juha and Kanerva, Anna and Pesonen,
Sari and Ahtiainen, Laura and Hemminki, Akseli},
title = {Mre11 inhibition by oncolytic adenovirus associates with autophagy
and underlies synergy with ionizing radiation},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {2441--2449},
number = {10},
abstract = {Abstract 10.1002/ijc.24608.abs New treatment approaches are needed
for hormone refractory prostate cancer. Oncolytic adenoviruses are
promising anti-cancer agents, and their efficacy can be improved
by combining with conventional therapies such as ionizing radiation.
The aim of this study was to determine the timing of oncolytic adenovirus
treatment with regard to radiation and study the mechanisms of synergy
in combination treatment. Prostate cancer cells were infected with
oncolytic adenoviruses, irradiated and synergy mechanisms were assessed.
In vivo models of combination treatment were tested. Radiation and
oncolytic viruses were synergistic when viral infection was scheduled
24 hr after irradiation. Combination of oncolytic adenovirus with
radiotherapy significantly increased antitumor efficacy in vivo compared
to either agent alone. Microarray analysis showed dysregulated pathways
including cell cycle, mTOR and antigen processing pathways. Functional
analysis showed that adenoviral infection was accompanied with degradation
of proteins involved in DNA break repair. Mre11 was degraded for
subsequent inactivation of Chk2-Thr68 in combination treated cells,
while γH2AX-Ser139 was elevated implicating the persistence of DNA
double strand breaks. Increased autophagocytosis was seen in combination
treated cells. Combination treatment did not increase apoptosis or
virus replication. The results provide evidence of the antitumor
efficacy of combining oncolytic adenoviruses with irradiation as
a therapeutic strategy for the treatment of prostate cancer. Further,
these findings propose a molecular mechanism that may be important
in radiation induced cell death, autophagy and viral cytopathic effect.
© 2009 UICC},
issn = {1097-0215},
keywords = {oncolytic adenovirus, ionizing radiation, DNA repair inhibition, autophagy,
synergism},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24608}
}
@ARTICLE{Rajhi2011,
author = {Rajhi, Imene and Yamauchi, Takaki and Takahashi, Hirokazu and Nishiuchi,
Shunsaku and Shiono, Katsuhiro and Watanabe, Ryosuke and Mliki, Ahmed
and Nagamura, Yoshiaki and Tsutsumi, Nobuhiro and Nishizawa, Naoko
K. and Nakazono, Mikio},
title = {Identification of genes expressed in maize root cortical cells during
lysigenous aerenchyma formation using laser microdissection and microarray
analyses},
journal = {New Phytologist},
year = {2011},
volume = {190},
pages = {351--368},
number = {2},
abstract = {Summary
* •To adapt to waterlogging in soil, some gramineous plants, such
as maize (Zea mays), form lysigenous aerenchyma in the root cortex.
Ethylene, which is accumulated during waterlogging, promotes aerenchyma
formation. However, the molecular mechanism of aerenchyma formation
is not understood. * •The aim of this study was to identify aerenchyma
formation-associated genes expressed in maize roots as a basis for
understanding the molecular mechanism of aerenchyma formation. Maize
plants were grown under waterlogged conditions, with or without pretreatment
with an ethylene perception inhibitor 1-methylcyclopropene (1-MCP),
or under aerobic conditions. Cortical cells were isolated by laser
microdissection and their mRNA levels were examined with a microarray.
* •The microarray analysis revealed 575 genes in the cortical cells,
whose expression was either up-regulated or down-regulated under
waterlogged conditions and whose induction or repression was suppressed
by pretreatment with 1-MCP. * •The differentially expressed genes
included genes related to the generation or scavenging of reactive
oxygen species, Ca2+ signaling, and cell wall loosening and degradation.
The results of this study should lead to a better understanding of
the mechanism of root lysigenous aerenchyma formation.},
doi = {10.1111/j.1469-8137.2010.03535.x},
issn = {1469-8137},
keywords = {aerenchyma, ethylene, laser microdissection, maize (Zea mays), microarray,
programmed cell death},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2010.03535.x}
}
@ARTICLE{Rajkumar2010,
author = {Rajkumar, Revathi and Konishi, Kazuhisa and Richards, Thomas J. and
Ishizawar, David C. and Wiechert, Andrew C. and Kaminski, Naftali
and Ahmad, Ferhaan},
title = {Genomewide RNA expression profiling in lung identifies distinct signatures
in idiopathic pulmonary arterial hypertension and secondary pulmonary
hypertension},
journal = {Am J Physiol Heart Circ Physiol},
year = {2010},
volume = {298},
pages = {H1235--1248},
number = {4},
month = apr,
abstract = {Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening
condition characterized by pulmonary arteriolar remodeling. This
investigation aimed to identify genes involved specifically in the
pathogenesis of PAH and not other forms of pulmonary hypertension
(PH). Using genomewide microarray analysis, we generated the largest
data set to date of RNA expression profiles from lung tissue specimens
from 1) 18 PAH subjects and 2) 8 subjects with PH secondary to idiopathic
pulmonary fibrosis (IPF) and 3) 13 normal subjects. A molecular signature
of 4,734 genes discriminated among these three cohorts. We identified
significant novel biological changes that were likely to contribute
to the pathogenesis of PAH, including regulation of actin-based motility,
protein ubiquitination, and cAMP, transforming growth factor-{beta},
MAPK, estrogen receptor, nitric oxide, and PDGF signaling. Bone morphogenic
protein receptor type II expression was downregulated, even in subjects
without a mutation in this gene. Women with PAH had higher expression
levels of estrogen receptor 1 than normal women. Real-time quantitative
PCR confirmed differential expression of the following genes in PAH
relative to both normal controls and PH secondary to IPF: a disintegrin-like
and metalloprotease with thrombospondin type 1 motif 9, cell adhesion
molecule with homology to L1CAM, cytochrome b558 and {beta}-polypeptide,
coagulation factor II receptor-like 3, A-myb myeloblastosis viral
oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor
P2Y, platelet factor 4, phospholamban, and tropomodulin 3. This study
shows that PAH and PH secondary to IPF are characterized by distinct
gene expression signatures, implying distinct pathophysiological
mechanisms.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/298/4/H1235}
}
@ARTICLE{Rajput2004,
author = {Rajput, Ashish and Singh, Bhagirath},
title = {Gene expression profiling in type 1 diabetes prone NOD mice immunized
with a disease protective autoantigenic peptide},
journal = {Journal of Autoimmunity},
year = {2004},
volume = {23},
pages = {311--321},
number = {4},
month = dec,
abstract = {Immunization with autoantigenic peptides skews T cell responses in
type 1 diabetes (T1D), yet the gene-expression signature characterizing
this change is unclear. We used cDNA microarray technology to identify
genes differentially regulated in splenocytes of T1D prone NOD mice
after immunization with a disease protective glutamic acid decarboxylase
65 (GAD65 P14) peptide. We identified 96 genes involved in cytokine
secretion, humoral immune response, T cell activation, signal transduction,
cell proliferation, complement activation and inflammatory responses.
Up-regulation of seven chemokine and cytokine genes confirmed our
previous findings of increased interferon-[gamma] (IFN-[gamma]) secretion,
which may lead to a protective response in T1D. Hierarchical clustering
was used to organize treated and control groups on the basis of their
overall similarity in gene-expression patterns, suggesting association
or co-regulation. Semi-quantitative RT-PCR was used to confirm the
expression of selected genes in spleen and pancreatic draining lymph
nodes. These findings can be used to compare other immunization strategies
affecting the expression of these genes and explore their mechanisms
of action. This microarray-based study, thus, unravels the molecular
mechanism of [beta]-cell associated autoantigenic peptide immunization
in T1D prone NOD mice, paving the way for identification of diagnostic
markers and drug targets for modulating immune responses in T1D.},
issn = {0896-8411},
keywords = {GAD65 peptide, Autoantigens, Microarray, Th1 response, Type 1 diabetes},
url = {http://www.sciencedirect.com/science/article/B6WHC-4DPC58S-2/2/8432467b85a4b6189a09595fa1b6c2b2}
}
@ARTICLE{Raju2009,
author = {Raju, Bina and Hultström, Michael and Haug, Sivakami R. and Ibrahim,
Salah O. and Heyeraas, Karin J.},
title = {Sympathectomy suppresses tumor growth and alters gene-expression
profiles in rat tongue cancer},
journal = {European Journal of Oral Sciences},
year = {2009},
volume = {117},
pages = {351--361},
number = {4},
abstract = {Sympathetic nerves are known to affect carcinogenesis. Recently we
found that sympathetic denervation decreases the size of rat tongue
tumors. To identify genes involved in rat tongue carcinogenesis and
to study the effect of sympathetic nerves on these genes, we compared
gene-expression profiles in normal rat tongue (control) and in tumor-induced
tongues with (SCGx) and without (Sham) bilateral sympathectomy. Significance
analysis of microarrays revealed 280 genes (168 up-regulated, 112
down-regulated) that showed at least a twofold differential expression
between Sham and SCGx tumors (false discovery rate < 5%). These
included genes associated with cell adhesion, signaling, structure,
proliferation, metabolism, angiogenesis, development, and immunity.
Hierarchical clustering demonstrated that controls and sympathectomized
tumors grouped together, while Sham tumors grouped separately. We
identified 34 genes, known to be involved in carcinogenesis, that
were not differentially expressed between sympathectomized tumors
and control tongues, but which showed a significant change in expression
in Sham tumors. Microarray results of 12 of these genes were confirmed
by quantitative reverse transcription–polymerase chain reaction.
In conclusion, sympathectomy significantly altered the gene-expression
profile and inhibited tumor growth. The expression of several cancer
genes were increased more than threefold in Sham tumors, but unaltered
in the sympathectomized tumors when compared with controls, indicating
that these genes may be of significance in rat tongue carcinogenesis.},
issn = {1600-0722},
keywords = {gene-expression profile, microarrays, sympathectomy, tongue cancer},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0722.2009.00646.x}
}
@ARTICLE{RakiAe‡2006,
author = {Rakić, Bojana and Brûlotte, Marc and Rouleau, Yanouchka and Bélanger,
Sylvie and Pezacki, John Paul},
title = {Bleomycin is a Potent Small-Molecule Inhibitor of Hepatitis C Virus
Replication},
journal = {Chem. Eur. J. of Chem. Bio.},
year = {2006},
volume = {7},
pages = {1330--1333},
number = {9},
issn = {1439-7633},
keywords = {antiviral agents, bleomycin, hepatitis C, RNA, small-molecule inhibitors},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/cbic.200600180}
}
@ARTICLE{Rall2011,
author = {Rall, Katharina and Barresi, Gianmaria and Walter, Michael and Poths,
Sven and Haebig, Karina and Schaeferhoff, Karin and Schoenfisch,
Birgitt and Riess, Olaf and Wallwiener, Diethelm and Bonin, Michael
and Brucker, Sara},
title = {A combination of transcriptome and methylation analyses reveals embryologically-relevant
candidate genes in MRKH patients},
journal = {Orphanet Journal of Rare Diseases},
year = {2011},
volume = {6},
pages = {32},
number = {1},
abstract = {BACKGROUND:The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is present
in at least 1 out of 4,500 female live births and is the second most
common cause for primary amenorrhea. It is characterized by vaginal
and uterine aplasia in an XX individual with normal secondary characteristics.
It has long been considered a sporadic anomaly, but familial clustering
occurs. Several candidate genes have been studied although no single
factor has yet been identified. Cases of discordant monozygotic twins
suggest that the involvement of epigenetic factors is more likely.METHODS:Differences
in gene expression and methylation patterns of uterine tissue between
eight MRKH patients and eight controls were identified using whole-genome
microarray analyses. Results obtained by expression and methylation
arrays were confirmed by qRT-PCR and pyrosequencing.RESULTS:We delineated
293 differentially expressed and 194 differentially methylated genes
of which nine overlap in both groups. These nine genes are mainly
embryologically relevant for the development of the female genital
tract.CONCLUSION:Our study used, for the first time, a combined whole-genome
expression and methylation approach to reveal the etiology of the
MRKH syndrome. The findings suggest that either deficient estrogen
receptors or the ectopic expression of certain HOXA genes might lead
to abnormal development of the female reproductive tract. In utero
exposure to endocrine disruptors or abnormally high maternal hormone
levels might cause ectopic expression or anterior transformation
of HOXA genes. It is, however, also possible that different factors
influence the anti-Mullerian hormone promoter activity during embryological
development causing regression of the Mullerian ducts. Thus, our
data stimulate new research directions to decipher the pathogenic
basis of MRKH syndrome.},
doi = {10.1186/1750-1172-6-32},
issn = {1750-1172},
pubmedid = {21619687},
url = {http://www.ojrd.com/content/6/1/32}
}
@ARTICLE{Ramaglia2009,
author = {Ramaglia, Valeria and Tannemaat, Martijn Rudolf and de Kok, Maryla
and Wolterman, Ruud and Vigar, Miriam Ann and King, Rosalind Helen
Mary and Morgan, Bryan Paul and Baas, Frank},
title = {Complement inhibition accelerates regeneration in a model of peripheral
nerve injury},
journal = {Molecular Immunology},
year = {2009},
volume = {47},
pages = {302--309},
number = {2-3},
month = dec,
abstract = {Complement (C) activation is a crucial event in peripheral nerve degeneration
but its effect on the subsequent regeneration is unknown. Here we
show that genetic deficiency of the sixth C component, C6, accelerates
axonal regeneration and recovery in a rat model of sciatic nerve
injury. Foot-flick test and Sciatic Function Index monitored up to
5 weeks post-injury showed a significant improvement of sensory and
motor function in the C6 deficient animals compared to wildtypes.
Retrograde tracing experiments showed a significantly higher number
of regenerated neurons at 1 week post-injury in C6 deficient rats
than wildtypes. Pathology showed improved nerve regeneration in tibials
of C6 deficient animals compared to wildtypes. Reconstitution with
purified human C6 protein re-established the wildtype phenotype whereas
pharmacological inhibition of C activation with soluble C receptor
1 (sCR1) facilitated recovery and improved pathology similarly to
C6 deficient animals. We suggest that a destructive C-mediated event
during nerve degeneration hampers the subsequent regenerative process.
These findings provide a rationale for the testing of anti-complement
agents in human nerve injury.},
issn = {0161-5890},
keywords = {Crush injury, Complement, Complement inhibitors, Regeneration, Recovery},
url = {http://www.sciencedirect.com/science/article/B6T9R-4XFNCNH-1/2/515107be1c6de1d246cf3e88b3408b4c}
}
@ARTICLE{Ramakrishnan2008,
author = {Ramakrishnan, Girija and Meeker, Alexis and Dragulev, Bojan},
title = {fslE Is Necessary for Siderophore-Mediated Iron Acquisition in Francisella
tularensis Schu S4},
journal = {J. Bacteriol.},
year = {2008},
volume = {190},
pages = {5353--5361},
number = {15},
month = aug,
abstract = {Strains of Francisella tularensis secrete a siderophore in response
to iron limitation. Siderophore production is dependent on fslA,
the first gene in an operon that appears to encode biosynthetic and
export functions for the siderophore. Transcription of the operon
is induced under conditions of iron limitation. The fsl genes lie
adjacent to the fur homolog on the chromosome, and there is a canonical
Fur box sequence in the promoter region of fslA. We generated a {Delta}fur
mutant of the Schu S4 strain of F. tularensis tularensis and determined
that siderophore production was now constitutive and no longer regulated
by iron levels. Quantitative reverse transcriptase PCR analysis with
RNA from Schu S4 and the mutant strain showed that Fur represses
transcription of fslA under iron-replete conditions. We determined
that fslE (locus FTT0025 in the Schu S4 genome), located downstream
of the siderophore biosynthetic genes, is also under Fur regulation
and is transcribed as part of the fslABCDEF operon. We generated
a defined in-frame deletion of fslE and found that the mutant was
defective for growth under iron limitation. Using a plate-based growth
assay, we found that the mutant was able to secrete a siderophore
but was defective in utilization of the siderophore. FslE belongs
to a family of proteins that has no known homologs outside of the
Francisella species, and the fslE gene product has been previously
localized to the outer membrane of F. tularensis strains. Our data
suggest that FslE may function as the siderophore receptor in F.
tularensis.},
url = {http://jb.asm.org/cgi/content/abstract/190/15/5353}
}
@ARTICLE{Ramakrishnan2002,
author = {Ramakrishnan, Ramesh and Dorris, David and Lublinsky, Anna and Nguyen,
Allen and Domanus, Marc and Prokhorova, Anna and Gieser, Linn and
Touma, Edward and Lockner, Randall and Tata, Murthy and Zhu, Xiaomei
and Patterson, Marcus and Shippy, Richard and Sendera, Timothy J.
and Mazumder, Abhijit},
title = {An assessment of Motorola CodeLinkTM microarray performance for gene
expression profiling applications},
journal = {Nucleic Acids Res.},
year = {2002},
volume = {30},
pages = {e30--},
number = {7},
month = apr,
abstract = {DNA microarrays enable users to obtain information on differences
in transcript abundance on a massively parallel scale. Recently,
however, data analyses have revealed potential pitfalls related to
image acquisition, variability and misclassifications in replicate
measurements, cross-hybridization and sensitivity limitations. We
have generated a series of analytical tools to address the manufacturing,
detection and data analysis components of a microarray experiment.
Together, we have used these tools to optimize performance in an
expression profiling study. We demonstrate three significant advantages
of the Motorola CodeLinkTM platform: sensitivity of one copy per
cell, coefficients of variation of 10% in the hybridization signals
across slides and across target preparations, and specificity in
distinguishing highly homologous sequences. Slides where oligonucleotide
probes are spotted in 6-fold redundancy were used to demonstrate
the effect of replication on data quality. Lastly, the differential
expression ratios obtained with the CodeLinkTM expression platform
were validated against those obtained with quantitative reverse transcription-PCR
assays for 54 genes.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/30/7/e30}
}
@ARTICLE{Ramalingam2010,
author = {Ramalingam, Naveen and Rui, Zhang and Liu, Hao-Bing and Dai, Chang-Chun
and Kaushik, Rajni and Ratnaharika, Bandi and Gong, Hai-Qing},
title = {Real-time PCR-based microfluidic array chip for simultaneous detection
of multiple waterborne pathogens},
journal = {Sensors and Actuators B: Chemical},
year = {2010},
volume = {145},
pages = {543--552},
number = {1},
month = mar,
abstract = {We report disposable microfluidic devices harboring an array of unsealed
reactors, which are pre-loaded with different primer pairs for simultaneous
(parallel) real-time PCR-based detection of multiple waterborne pathogens.
The PCR mixture loading among an array of reactors and subsequent
isolation of the reactors was solely realized by a single step capillary-based
flow scheme, which eliminates the use of pumps, valves and liquid
handling instruments. We incorporated a localized thermal cycling
scheme to minimize evaporative loss of PCR mixture in unsealed microreactors,
which greatly reduces the complexity of the microfabrication and
fluidic operation process, in cases, where valving or sealing of
the reactors for PCR thermal cycling is required. Experiments were
performed to determine the optimal microreactor design parameters,
so as to perform bubble-free PCR with minimal evaporative loss in
unsealed reactors. The potential of the microfluidic device was successfully
demonstrated by specifically detecting genomic DNA of waterborne
pathogens from a pool of genomic DNA template.},
issn = {0925-4005},
keywords = {Microreactor array, Capillary microfluidics, Microchip PCR, Real-time
PCR, Pathogen detection},
url = {http://www.sciencedirect.com/science/article/B6THH-4XRYT4R-4/2/d0b345ac242dab254f681edfab0af429}
}
@ARTICLE{Raman2009,
author = {Raman, Tina and O'Connor, Timothy and Hackett, Neil and Wang, Wei
and Harvey, Ben-Gary and Attiyeh, Marc and Dang, David and Teater,
Matthew and Crystal, Ronald},
title = {Quality control in microarray assessment of gene expression in human
airway epithelium},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {493},
number = {1},
abstract = {BACKGROUND:Microarray technology provides a powerful tool for defining
gene expression profiles of airway epithelium that lend insight into
the pathogenesis of human airway disorders. The focus of this study
was to establish rigorous quality control parameters to ensure that
microarray assessment of the airway epithelium is not confounded
by experimental artifact. Samples (total n = 223) of trachea, large
and small airway epithelium were collected by fiberoptic bronchoscopy
of 144 individuals and hybridized to Affymetrix microarrays. The
pre- and post-chip quality control (QC) criteria established, included:
(1) RNA quality, assessed by RNA Integrity Number (RIN) = 7.0; (2)
cRNA transcript integrity, assessed by signal intensity ratio of
GAPDH 3' to 5' probe sets = 3.0; and (3) the multi-chip normalization
scaling factor = 10.0.RESULTS:Of the 223 samples, all three criteria
were assessed in 191; of these 184 (96.3%) passed all three criteria.
For the remaining 32 samples, the RIN was not available, and only
the other two criteria were used; of these 29 (90.6%) passed these
two criteria. Correlation coefficients for pairwise comparisons of
expression levels for 100 maintenance genes in which at least one
array failed the QC criteria (average Pearson r = 0.90 ± 0.04) were
significantly lower (p < 0.0001) than correlation coefficients for
pairwise comparisons between arrays that passed the QC criteria (average
Pearson r = 0.97 ± 0.01). Inter-array variability was significantly
decreased (p < 0.0001) among samples passing the QC criteria compared
with samples failing the QC criteria.CONCLUSION:Based on the aberrant
maintenance gene data generated from samples failing the established
QC criteria, we propose that the QC criteria outlined in this study
can accurately distinguish high quality from low quality data, and
can be used to delete poor quality microarray samples before proceeding
to higher-order biological analyses and interpretation.},
doi = {10.1186/1471-2164-10-493},
issn = {1471-2164},
pubmedid = {19852842},
url = {http://www.biomedcentral.com/1471-2164/10/493}
}
@ARTICLE{Ramanathan2008,
author = {Ramanathan, Palaniappan and Martin, Ian and Gardiner-Garden, Margaret
and Thomson, Peter and Taylor, Rosanne and Ormandy, Christopher and
Moran, Christopher and Williamson, Peter},
title = {Transcriptome analysis identifies pathways associated with enhanced
maternal performance in QSi5 mice},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {197},
number = {1},
abstract = {BACKGROUND:Highly fecund mouse strains provide an ideal model to understand
the factors affecting maternal performance. The QSi5 inbred strain
of mice was selected for high fecundity and low inter-litter interval,
and is very successful at weaning large numbers of offspring when
compared to other inbred strains.RESULTS:Post-natal pup weight gain
was used to estimate mammary gland output and to compare the performance
of QSi5 mice to CBA mice. Cumulative litter weights and individual
pup weight gain was significantly higher throughout the first eight
days of lactation in QSi5 mice compared to CBA mice. Morphometric
analysis of mammary glands during pregnancy in QSi5 mice revealed
a 150 percent greater ductal side branching compared to CBA mice
(P < 0.001). Ontology and pathway classification of transcript profiles
from the two strains identified an enrichment of genes involved in
a number of pathways, including the MAPK, tight junction, insulin
signalling and Wnt signalling. Eleven of these genes, including six
genes from the MAPK signalling pathway, were identified as associated
with postnatal growth. Further, positive mediators of Wnt signalling,
including Wnt4, Csnk2a1 and Smad4, were over-represented in the QSi5
strain profile, while negative regulators, including Dkkl1, Ppp2r1a
and Nlk, were under-represented. These findings are consistent with
the role of Wnt and MAPK signalling pathway in ductal morphogenesis
and lobuloalveolar development suggesting enhanced activity in QSi5
mice. A similar pattern of phenotype concordance was seen amongst
12 genes from the tight junction pathway, but a pattern did not emerge
from the insulin signalling genes. Amongst a group of differentially
expressed imprinted genes, two maternal imprinted genes that suppress
growth induced via the IGF signalling pathway, Grb10 and Igf2r, were
under-represented in QSi5 mice. Whereas Peg3 and Plagl1, both paternally
imprinted genes that enhance neonatal growth, were over-represented
in QSi5 mice.CONCLUSION:We propose that the combined action of at
least three major signalling pathways involved in mammary gland development
and milk secretion, namely Wnt, MAPK and tight junction pathways,
contribute to the superior maternal performance phenotype in QSi5
mice. Additionally, favourable expression patterns of the imprinted
genes Peg3, Plagl1, Grb10 and Igf2r may also contribute.},
doi = {10.1186/1471-2164-9-197},
issn = {1471-2164},
pubmedid = {18442417},
url = {http://www.biomedcentral.com/1471-2164/9/197}
}
@ARTICLE{Rambow2008,
author = {Rambow, F. and Malek, O. and Geffrotin, C. and Leplat, J.-J. and
Bouet, S. and Piton, G. and Hugot, K. and Bevilacqua, C. and Horak,
V. and Vincent-Naulleau, S.},
title = {Identification of differentially expressed genes in spontaneously
regressing melanoma using the MeLiM Swine Model},
journal = {Pigment Cell \& Melanoma Research},
year = {2008},
volume = {21},
pages = {147--161},
number = {2},
abstract = {Summary Partial and some few cases of complete spontaneous regression
have been observed in cutaneous melanoma patients but little is known
about the molecular mechanisms involved. The Melanoblastoma-bearing
Libechov Minipig (MeLiM) is a suitable animal model to study the
phenomenon of spontaneous regression because MeLiM pigs exhibit naturally
occurring melanomas which regress completely 6Â months after birth.
In this study, we used suppression subtractive hybridization (SSH)
to identify molecular determinants of melanoma regression within
swine melanoma tissues and melanoma cell cultures. Several markers
involved in cell-adhesion, -communication, -motility, signal transduction,
negative regulation of cell proliferation, transport and immune response
were identified that correlated with melanoma regression whereas
the main genes involved in melanin synthesis showed a strong downregulation.
For the most differentially expressed genes, we validated the results
obtained by SSH with qRT-PCR and with immunohistochemistry for some
of them (CD9, MITF, RARRES1). Most notable, for the first time in
melanoma, we identified the retinoic acid responder 1 gene (RARRES1)
as a main actor of the regression process in melanoma. This first
gene expression study in swine melanoma regression, may contribute
to the finding of new therapeutic targets for human melanoma treatment.},
issn = {1755-148X},
keywords = {Swine melanoma, suppression subtractive hybridization, differential
gene expression, real-time PCR, tumour regression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-148X.2008.00442.x}
}
@ARTICLE{Ramdas2009,
author = {Ramdas, Latha and Giri, Uma and Ashorn, Cheryl L. and Coombes, Kevin
R. and El-Naggar, Adel and Ang, K. Kian and Story, Michael D.},
title = {miRNA expression profiles in head and neck squamous cell carcinoma
and adjacent normal tissue},
journal = {Head Neck},
year = {2009},
volume = {31},
pages = {642--654},
number = {5},
abstract = {Abstract 10.1002/hed.21017.abs Background. The expression of miRNA
in head and neck squamous cell carcinomas (HNSCCs) that had been
classified as high risk by surgical pathologic features and validated
by trial outcome for disease recurrence was determined and compared
with matched adjacent normal tissues. Methods. miRNA and corresponding
gene expression were determined using miRNA bioarrays and gene expression
arrays. Results. Twenty miRNAs were determined to be differentially
regulated in the HNSCC samples when compared with their normal tissue
counterparts. Quantitative reverse transcriptase-polymerase chain
reaction confirmed differential regulation of miRNA expression, and
gene expression analysis on these same-paired samples confirmed the
loss of putative mRNA targets including genes such as adenomatous
polyposis coli, programmed cell death protein 4, and TGF beta receptor
3 in the tumor samples. Conclusions. These data suggest a role for
the upregulation of specific miRNAs in high-risk HNSCC. Furthermore,
upregulation of these miRNAs may be responsible for the elimination
of mRNAs that lead to the growth and progression of HNSCC. © 2009
Wiley Periodicals, Inc. Head Neck, 2009},
issn = {1097-0347},
keywords = {HNSCC, miRNA, miRNA targets, gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hed.21017}
}
@ARTICLE{Ramel2007,
author = {Ramel, Fanny and Sulmon, Cécile and Cabello-Hurtado, Francisco and
Taconnat, Ludivine and Martin-Magniette, Marie-Laure and Renou, Jean-Pierre
and El Amrani, Abdelhak and Couée, Ivan and Gouesbet, Gwenola},
title = {Genome-wide interacting effects of sucrose and herbicide-mediated
stress in Arabidopsis thaliana: novel insights into atrazine toxicity
and sucrose-induced tolerance},
journal = {BMC Genomics},
year = {2007},
volume = {8},
pages = {450},
number = {1},
abstract = {BACKGROUND:Soluble sugars, which play a central role in plant structure
and metabolism, are also involved in the responses to a number of
stresses, and act as metabolite signalling molecules that activate
specific or hormone-crosstalk transduction pathways. The different
roles of exogenous sucrose in the tolerance of Arabidopsis thaliana
plantlets to the herbicide atrazine and oxidative stress were studied
by a transcriptomic approach using CATMA arrays.RESULTS:Parallel
situations of xenobiotic stress and sucrose-induced tolerance in
the presence of atrazine, of sucrose, and of sucrose plus atrazine
were compared. These approaches revealed that atrazine affected gene
expression and therefore seedling physiology at a much larger scale
than previously described, with potential impairment of protein translation
and of reactive-oxygen-species (ROS) defence mechanisms. Correlatively,
sucrose-induced protection against atrazine injury was associated
with important modifications of gene expression related to ROS defence
mechanisms and repair mechanisms. These protection-related changes
of gene expression did not result only from the effects of sucrose
itself, but from combined effects of sucrose and atrazine, thus strongly
suggesting important interactions of sucrose and xenobiotic signalling
or of sucrose and ROS signalling.CONCLUSION:These interactions resulted
in characteristic differential expression of gene families such as
ascorbate peroxidases, glutathione-S-transferases and cytochrome
P450s, and in the early induction of an original set of transcription
factors. These genes used as molecular markers will eventually be
of great importance in the context of xenobiotic tolerance and phytoremediation.},
doi = {10.1186/1471-2164-8-450},
issn = {1471-2164},
owner = {Meike Kuschel},
pubmedid = {18053238},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2164/8/450}
}
@ARTICLE{Ramelet2009,
author = {Ramelet, Albert-Adrien and Hirt-Burri, Nathalie and Raffoul, Wassim
and Scaletta, Corinne and Pioletti, Dominique P. and Offord, Elizabeth
and Mansourian, Robert and Applegate, Lee Ann},
title = {Chronic wound healing by fetal cell therapy may be explained by differential
gene profiling observed in fetal versus old skin cells},
journal = {Experimental Gerontology},
year = {2009},
volume = {44},
pages = {208--218},
number = {3},
month = mar,
abstract = {Engineering of fetal tissue has a high potential for the treatment
of acute and chronic wounds of the skin in humans as these cells
have high expansion capacity under simple culture conditions and
one organ donation can produce Master Cell Banks which can fabricate
over 900 million biological bandages (9 × 12 cm). In a Phase 1 clinical
safety study, cases are presented for the treatment of therapy resistant
leg ulcers. All eight patients, representing 13 ulcers, tolerated
multiple treatments with fetal biological bandages showing no negative
secondary effects and repair processes similar to that seen in 3rd
degree burns. Differential gene profiling using Affymetrix gene chips
(analyzing 12,500 genes) were accomplished on these banked fetal
dermal skin cells compared to banked dermal skin cells of an aged
donor in order to point to potential indicators of wound healing.
Families of genes involved in cell adhesion and extracellular matrix,
cell cycle, cellular signaling, development and immune response show
significant differences in regulation between banked fetal and those
from banked old skin cells: with approximately 47.0% of genes over-expressed
in fetal fibroblasts. It is perhaps these differences which contribute
to efficient tissue repair seen in the clinic with fetal cell therapy.},
issn = {0531-5565},
keywords = {Fetal skin, Chronic wounds, Tissue engineering, Gene families, Extracellular
matrix, Growth factors, Leg ulcers},
url = {http://www.sciencedirect.com/science/article/B6T6J-4TYR061-1/2/f95b02d5fdbfb9038e26de67f08e4065}
}
@ARTICLE{Ramilo2007,
author = {Ramilo, Octavio and Allman, Windy and Chung, Wendy and Mejias, Asuncion
and Ardura, Monica and Glaser, Casey and Wittkowski, Knut M. and
Piqueras, Bernard and Banchereau, Jacques and Palucka, A. Karolina
and Chaussabel, Damien},
title = {Gene expression patterns in blood leukocytes discriminate patients
with acute infections},
journal = {Blood},
year = {2007},
volume = {109},
pages = {2066--2077},
number = {5},
month = mar,
abstract = {Each infectious agent represents a unique combination of pathogen-associated
molecular patterns that interact with specific pattern-recognition
receptors expressed on immune cells. Therefore, we surmised that
the blood immune cells of individuals with different infections might
bear discriminative transcriptional signatures. Gene expression profiles
were obtained for 131 peripheral blood samples from pediatric patients
with acute infections caused by influenza A virus, Gram-negative
(Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus
pneumoniae) bacteria. Thirty-five genes were identified that best
discriminate patients with influenza A virus infection from patients
with either E coli or S pneumoniae infection. These genes classified
with 95% accuracy (35 of 37 samples) an independent set of patients
with either influenza A, E coli, or S pneumoniae infection. A different
signature discriminated patients with E coli versus S aureus infections
with 85% accuracy (34 of 40). Furthermore, distinctive gene expression
patterns were observed in patients presenting with respiratory infections
of different etiologies. Thus, microarray analyses of patient peripheral
blood leukocytes might assist in the differential diagnosis of infectious
diseases.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/5/2066}
}
@ARTICLE{Ramirez2009,
author = {Ramirez, Jean-Marie and Schaad, Olivier and Durual, Stephane and
Cossali, Dominique and Docquier, Mylène and Beris, Photis and Descombes,
Patrick and Matthes, Thomas},
title = {Growth differentiation factor 15 production is necessary for normal
erythroid differentiation and is increased in refractory anaemia
with ring-sideroblasts},
journal = {British Journal of Haematology},
year = {2009},
volume = {144},
pages = {251--262},
number = {2},
abstract = {Summary The disturbed erythropoiesis in patients with refractory anaemia
with ring-sideroblasts (RARS) is characterized by intramedullary
apoptosis of erythroid precursors and increased iron accumulation
in mitochondria. To gain insight into these pathophysiological mechanisms
we compared the gene expression profile (GEP) of erythroid precursors
from RARS patients to the GEP of normal erythroid precursors. Three
hundred sixty four probe sets were up-, and 253 probe sets downregulated
in RARS cells. Interestingly, Growth Differentiation factor 15 (GDF15),
a cytokine from the TGFβ family, was dramatically upregulated in
all RARS patients. Measurement of GDF15 in the sera from twenty RARS
patients confirmed this finding by showing significantly, 7·2-fold,
increased protein levels (3254 ± 1400 ng/ml vs. 451 ± 87 ng/ml
in normals). In vitro studies demonstrated erythroid-specific production
of GDF15 and dependence on erythropoietin. Induction of apoptosis
by arsenic trioxide, a drug which acts via reduction of the mitochondrial
membrane potential, also stimulated GDF15 production. Downregulation
of endogenous GDF15 production in erythoblasts by specific siRNA
led to diminished erythroid differentiation. Taken together, our
findings demonstrate a new role for GDF15 in normal erythropoiesis
as well as in the ineffective erythropoiesis of RARS patients.},
issn = {1365-2141},
keywords = {erythropoiesis, growth differentiation factor 15, gene expression,
sideroblastic anaemia, apoptosis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2008.07441.x}
}
@ARTICLE{Ramirez2011,
author = {Ramirez, Vicente and Agorio, Astrid and Coego, Alberto and Garcia-Andrade,
Javier and Hernandez, M. Jose and Balaguer, Begona and Ouwerkerk,
Pieter B.F. and Zarra, Ignacio and Vera, Pablo},
title = {MYB46 Modulates Disease Susceptibility to Botrytis cinerea in Arabidopsis},
journal = {Plant Physiology},
year = {2011},
volume = {155},
pages = {1920--1935},
number = {4},
month = apr,
abstract = {In this study, we show that the Arabidopsis (Arabidopsis thaliana)
transcription factor MYB46, previously described to regulate secondary
cell wall biosynthesis in the vascular tissue of the stem, is pivotal
for mediating disease susceptibility to the fungal pathogen Botrytis
cinerea. We identified MYB46 by its ability to bind to a new cis-element
located in the 5' promoter region of the pathogen-induced Ep5C gene,
which encodes a type III cell wall-bound peroxidase. We present genetic
and molecular evidence indicating that MYB46 modulates the magnitude
of Ep5C gene induction following pathogenic insults. Moreover, we
demonstrate that different myb46 knockdown mutant plants exhibit
increased disease resistance to B. cinerea, a phenotype that is accompanied
by selective transcriptional reprogramming of a set of genes encoding
cell wall proteins and enzymes, of which extracellular type III peroxidases
are conspicuous. In essence, our results substantiate that defense-related
signaling pathways and cell wall integrity are interconnected and
that MYB46 likely functions as a disease susceptibility modulator
to B. cinerea through the integration of cell wall remodeling and
downstream activation of secondary lines of defense.},
comment = {10.1104/pp.110.171843},
url = {http://www.plantphysiol.org/cgi/content/abstract/155/4/1920}
}
@ARTICLE{Ramirez-Valle2008,
author = {Ramirez-Valle, Francisco and Braunstein, Steve and Zavadil, Jiri
and Formenti, Silvia C. and Schneider, Robert J.},
title = {eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition
of autophagy},
journal = {J. Cell Biol.},
year = {2008},
volume = {181},
pages = {293--307},
number = {2},
month = apr,
abstract = {Translation initiation factors have complex functions in cells that
are not yet understood. We show that depletion of initiation factor
eIF4GI only modestly reduces overall protein synthesis in cells,
but phenocopies nutrient starvation or inhibition of protein kinase
mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation,
bioenergetics, and mitochondrial activity, thereby promoting autophagy.
Translation of mRNAs involved in cell growth, proliferation, and
bioenergetics were selectively inhibited by reduction of eIF4GI,
as was the mRNA encoding Skp2 that inhibits p27, whereas catabolic
pathway factors were increased. Depletion or overexpression of other
eIF4G family members did not recapitulate these results. The majority
of mRNAs that were translationally impaired with eIF4GI depletion
were excluded from polyribosomes due to the presence of multiple
upstream open reading frames and low mRNA abundance. These results
suggest that the high levels of eIF4GI observed in many breast cancers
might act to specifically increase proliferation, prevent autophagy,
and release tumor cells from control by nutrient sensing.},
url = {http://jcb.rupress.org/cgi/content/abstract/181/2/293}
}
@ARTICLE{Ramot2010,
author = {Ramot, Yuval and Biro, Tamas and Tiede, Stephan and Toth, Balazs
I. and Langan, Ewan A. and Sugawara, Koji and Foitzik, Kerstin and
Ingber, Arieh and Goffin, Vincent and Langbein, Lutz and Paus, Ralf},
title = {Prolactin--a novel neuroendocrine regulator of human keratin expression
in situ},
journal = {FASEB J},
year = {2010},
volume = {24},
pages = {1768--1779},
number = {6},
month = jun,
abstract = {The controls of human keratin expression in situ remain to be fully
elucidated. Here, we have investigated the effects of the neurohormone
prolactin (PRL) on keratin expression in a physiologically and clinically
relevant test system: organ-cultured normal human hair follicles
(HFs). Not only do HFs express a wide range of keratins, but they
are also a source and target of PRL. Microarray analysis revealed
that PRL differentially regulated a defined subset of keratins and
keratin-associated proteins. Quantitative immunohistomorphometry
and quantitative PCR confirmed that PRL up-regulated expression of
keratins K5 and K14 and the epithelial stem cell-associated keratins
K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes.
PRL also up-regulated K15 promoter activity and K15 protein expression
in situ, whereas it inhibited K6 and K31 expression. These regulatory
effects were reversed by a pure competitive PRL receptor antagonist.
Antagonist alone also modulated keratin expression, suggesting that
"tonic stimulation" by endogenous PRL is required for normal expression
levels of selected keratins. Therefore, our study identifies PRL
as a major, clinically relevant, novel neuroendocrine regulator of
both human keratin expression and human epithelial stem cell biology
in situ.--Ramot, Y., Biro, T., Tiede, S. Toth, B. I., Langan, E.
A., Sugawara, K., Foitzik, K., Ingber, A., Goffin, V., Langbein,
L., Paus, R. Prolactin--a novel neuroendocrine regulator of human
keratin expression in situ.},
url = {http://www.fasebj.org/cgi/content/abstract/24/6/1768}
}
@ARTICLE{Rampazzo2007,
author = {Rampazzo, Chiara and Fabris, Sonia and Franzolin, Elisa and Crovatto,
Katia and Frangini, Miriam and Bianchi, Vera},
title = {Mitochondrial Thymidine Kinase and the Enzymatic Network Regulating
Thymidine Triphosphate Pools in Cultured Human Cells},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {34758--34769},
number = {48},
month = nov,
abstract = {In non-proliferating cells mitochondrial (mt) thymidine kinase (TK2)
salvages thymidine derived from the extracellular milieu for the
synthesis of mt dTTP. TK2 is a synthetic enzyme in a network of cytosolic
and mt proteins with either synthetic or catabolic functions regulating
the dTTP pool. In proliferating cultured cells the canonical cytosolic
ribonucleotide reductase (R1-R2) is the prominent synthetic enzyme
that by de novo synthesis provides most of dTTP for mt DNA replication.
In non-proliferating cells p53R2 substitutes for R2. Catabolic enzymes
safeguard the size of the dTTP pool: thymidine phosphorylase by degradation
of thymidine and deoxyribonucleotidases by degradation of dTMP. Genetic
deficiencies in three of the participants in the network, TK2, p53R2,
or thymidine phosphorylase, result in severe mt DNA pathologies.
Here we demonstrate the interdependence of the different enzymes
of the network. We quantify changes in the size and turnover of the
dTTP pool after inhibition of TK2 by RNA interference, of p53R2 with
hydroxyurea, and of thymidine phosphorylase with 5-bromouracil. In
proliferating cells the de novo pathway dominates, supporting large
cytosolic and mt dTTP pools, whereas TK2 is dispensable, even in
cells lacking the cytosolic thymidine kinase. In non-proliferating
cells the small dTTP pools depend on the activities of both R1-p53R2
and TK2. The activity of TK2 is curbed by thymidine phosphorylase,
which degrades thymidine in the cytoplasm, thus limiting the availability
of thymidine for phosphorylation by TK2 in mitochondria. The dTTP
pool shows an exquisite sensitivity to variations of thymidine concentrations
at the nanomolar level.},
url = {http://www.jbc.org/cgi/content/abstract/282/48/34758}
}
@ARTICLE{Rampon2008,
author = {Rampon, Christine and Bouillot, Stephanie and Climescu-Haulica, Adriana
and Prandini, Marie-Helene and Cand, Francine and Vandenbrouck, Yves
and Huber, Philippe},
title = {Protocadherin 12 deficiency alters morphogenesis and transcriptional
profile of the placenta},
journal = {Physiol Genomics},
year = {2008},
volume = {34},
pages = {193--204},
number = {2},
month = jul,
abstract = {Protocadherins are transmembrane proteins exhibiting homophilic adhesive
activities through their extracellular domain. Protocadherin 12 (Pcdh12)
is expressed in angiogenic endothelial cells, mesangial cells of
kidney glomeruli, and glycogen cells of the mouse placenta. To get
insight into the role of this protein in vivo, we analyzed PCDH12-deficient
mice and investigated their placental phenotype. The mice were alive
and fertile; however, placental and embryonic sizes were reduced
compared with wild-type mice. We observed defects in placental layer
segregation and a decreased vascularization of the labyrinth associated
with a reduction in cell density in this layer. To understand the
molecular events responsible for the phenotypic alterations observed
in Pcdh12-/- placentas, we analyzed the expression profile of embryonic
day 12.5 mutant placentas compared with wild-type placentas, using
pangenomic chips: 2,289 genes exhibited statistically significant
changes in expressed levels due to loss of PCDH12. Functional grouping
of modified genes was obtained by GoMiner software. Gene clusters
that contained most of the differentially expressed genes were those
involved in tissue morphogenesis and development, angiogenesis, cell-matrix
adhesion and migration, immune response, and chromatin remodeling.
Our data show that loss of PCDH12 leads to morphological alterations
of the placenta and to notable changes in its gene expression profile.
Specific genes emerging from the microarray screen support the biological
modifications observed in PCDH12-deficient placentas.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/34/2/193}
}
@ARTICLE{Ramsborg2007,
author = {Ramsborg, Christopher G. and Papoutsakis, E. Terry},
title = {Global transcriptional analysis delineates the differential inflammatory
response interleukin-15 elicits from cultured human T cells},
journal = {Experimental Hematology},
year = {2007},
volume = {35},
pages = {454--464.e4},
number = {3},
month = mar,
abstract = {Objective Interleukin 15 (IL)-15 controls proliferation and survival
of T cells, but its effects and the underlying cellular regulation
are not well understood. Previous studies have focused on its effects
on short-term T-cell cultures. In view of the potential problems
associated with using IL-2 alone in adoptive immunotherapy protocols,
we investigated the impact of IL-15 on T-cell cultures and the global
transcriptional effects it elicits in such cultures.Materials and
Methods DNA microarrays and flow cytometry were used to examine the
differential effect of 20 ng/mL IL-15 on primary serum-free T-cell
cultures activated and cultured in the presence of IL-2. Quantitative
reverse transcriptase polymerase chain reaction confirmed select
microarray data.Results IL-15 significantly increased ex vivo expansion
of primary human T cells over the entire 11-day expansions without
affecting viability. The 1133 genes were consistently differentially
expressed among three donor samples. Ontological analysis demonstrated
that IL-15 increases expression of genes involved in inflammatory
response (e.g., tumor necrosis factor [TNF]-[alpha], Oncostatin M,
CD40L, and CD33) and apoptosis (e.g., TNF-related apoptosis-inducing
ligand). IL-15 also induced expression of four suppressors of cytokine
signaling (SOCS) family genes (SOCS1-3, cytokine-inducible SH2-containing
protein), which are classical negative regulators of cytokine signaling.
IL-15 strongly suppressed the expression of inhibitory natural killer
cell receptor genes, including three C-type lectins (KLRB1, KLRC1,
and KLRD1), as well as IL-7Ra and Granzyme H. Finally, IL-15 induced
differential expression of TNF receptor superfamily members (CD27
and CD30).Conclusion These findings suggest that exogenous IL-15
may have a potential role in adoptive immunotherapy by both enhancing
proliferation and modulating functionality during ex vivo T-cell
expansion.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4N3D70J-G/2/cc21ce644f179ea27c3340e4f6e010e9}
}
@ARTICLE{Ramsden2011,
author = {Ramsden, Christopher and Mann, J Douglas and Faurot, Keturah and
Lynch, Chanee and Imam, Syed and MacIntosh, Beth and Hibbeln, Joseph
and Loewke, James and Smith, Sunyata and Coble, Rebecca and Suchindran,
Chirayath and Gaylord, Susan},
title = {Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention
for Chronic Daily Headache: Protocol for a randomized clinical trial},
journal = {Trials},
year = {2011},
volume = {12},
pages = {97},
number = {1},
abstract = {BACKGROUND:Targeted analgesic dietary interventions are a promising
strategy for alleviating pain and improving quality of life in patients
with persistent pain syndromes, such as chronic daily headache (CDH).
High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs),
linoleic acid (LA) and arachidonic acid (AA) may promote physical
pain by increasing the abundance, and subsequent metabolism, of LA
and AA in immune and nervous system tissues. Here we describe methodology
for an ongoing randomized clinical trial comparing the metabolic
and clinical effects of a low n-6, average n-3 PUFA diet, to the
effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH.
Our primary aim is to determine if: A) both diets reduce n-6 PUFAs
in plasma and erythrocyte lipid pools, compared to baseline; and
B) the low n-6 plus high n-3 diet produces a greater decline in n-6
PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes
include headache-specific quality-of-life, and headache frequency
and intensity.METHODS:Adults meeting the International Classification
of Headache Disorders criteria for CDH are included. After a 6-week
baseline phase, participants are randomized to a low n-6 diet, or
a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient
intake targets are provided for 2 meals and 2 snacks per day. A research
dietitian provides intensive dietary counseling at 2-week intervals.
Web-based intervention materials complement dietitian advice. Blood
and clinical outcome data are collected every 4 weeks.RESULTS:Subject
recruitment and retention has been excellent; 35 of 40 randomized
participants completed the 12-week intervention. Preliminary blinded
analysis of composite data from the first 20 participants found significant
reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases
in n-3 EPA, DHA and the omega-3 index, indicating adherence.TRIAL
REGISTRATION:ClinicalTrials.gov (NCT01157208)},
doi = {10.1186/1745-6215-12-97},
issn = {1745-6215},
pubmedid = {21496264},
url = {http://www.trialsjournal.com/content/12/1/97}
}
@ARTICLE{Ramsey2007,
author = {Ramsey, Victoria G. and Doherty, Jason M. and Chen, Christopher C.
and Stappenbeck, Thaddeus S. and Konieczny, Stephen F. and Mills,
Jason C.},
title = {The maturation of mucus-secreting gastric epithelial progenitors
into digestive-enzyme secreting zymogenic cells requires Mist1},
journal = {Development},
year = {2007},
volume = {134},
pages = {211--222},
number = {1},
month = jan,
abstract = {Continuous regeneration of digestive enzyme (zymogen)-secreting chief
cells is a normal aspect of stomach function that is disrupted in
precancerous lesions (e.g. metaplasias, chronic atrophy). The cellular
and genetic pathways that underlie zymogenic cell (ZC) differentiation
are poorly understood. Here, we describe a gene expression analysis
of laser capture microdissection purified gastric cell populations
that identified the bHLH transcription factor Mist1 as a potential
ZC regulatory factor. Our molecular and ultrastructural analysis
of proliferation, migration and differentiation of the gastric unit
in Mist1-/- and control mice supports a model whereby wild-type ZC
progenitors arise as neck cells in the proliferative (isthmal) zone
of the gastric unit and become transitional cells (TCs) with molecular
and ultrastructural characteristics of both enzyme-secreting ZCs
and mucus-secreting neck cells as they migrate to the neck-base zone
interface. Thereafter, they rapidly differentiate into mature ZCs
as they enter the base. By contrast, Mist1-/- neck cells differentiate
normally, but ZCs in the mature, basal portion of the gastric unit
uniformly exhibit multiple apical cytoplasmic structural abnormalities.
This defect in terminal ZC differentiation is also associated with
markedly increased abundance of TCs, especially in late-stage TCs
that predominantly have features of immature ZCs. Thus, we present
an in vivo system for analysis of ZC differentiation, present molecular
evidence that ZCs differentiate from neck cell progenitors and identify
Mist1 as the first gene with a role in this clinically important
process.},
url = {http://dev.biologists.org/cgi/content/abstract/134/1/211}
}
@ARTICLE{Ran2006,
author = {Ran, Jianmin and Hirano, Tsutomu and Fukui, Tomoyasu and Saito, Kiyomi
and Kageyama, Haruaki and Okada, Kenta and Adachi, Mitsuru},
title = {Angiotensin II infusion decreases plasma adiponectin level via its
type 1 receptor in rats: an implication for hypertension-related
insulin resistance},
journal = {Metabolism},
year = {2006},
volume = {55},
pages = {478--488},
number = {4},
month = apr,
abstract = {We explored the mechanisms underlying the close association between
hypertension and insulin resistance by measuring the changes in the
plasma levels of adiponectin, a novel insulin sensitizer secreted
by adipose tissue, in rats infused with angiotensin II (AII). Angiotensin
II (100 ng/kg per minute) was subcutaneously infused with osmotic
minipumps for 2 weeks in rats fed with either standard chow or a
high-fructose diet. Insulin sensitivity index (SI) was assessed by
the minimal model of Bergman [Diabetes 1989;38:1512-27]. Angiotensin
II infusion significantly increased blood pressure and decreased
SI. Angiotensin II decreased plasma adiponectin levels from 3.7 to
2.9 [mu]g/mL (P < .01) without affecting the expression of adiponectin
messenger RNA in adipose tissue. Angiotensin II infusion did not
affect plasma leptin and tumor necrosis factor [alpha] levels. An
AII type 1 receptor blocker, olmesartan, restored the low adiponectinemia
induced by the AII infusion (50 ng/kg per minute). Plasma adiponectin
levels were significantly lower in fructose-fed rats (2.3 [mu]g/mL)
than in chow-fed rats. Angiotensin II induced no further decrease
of adiponectin, whereas olmesartan increased adiponectin remarkably
both with and without AII infusion. The AII type 2 receptor blocker
PD123319 left the AII-induced hypoadiponectinemia unchanged in both
chow- and fructose-fed rats. The AII type 2 receptor agonist CGP42112A
also left the adiponectin unchanged. Plasma adiponectin levels were
substantially correlated with SI (r = 0.61, P < .0001). These results
suggest that AII suppresses adiponectin production via AII type 1
receptor, resulting in impaired insulin sensitivity.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/B6WN4-4JH1H8B-D/2/6ad2212e6b5875ff4fac756394a5625a}
}
@ARTICLE{Ranade2009,
author = {Ranade, Swati S. and Chung, Christina Bormann and Zon, Gerald and
Boyd, Victoria L.},
title = {Preparation of genome-wide DNA fragment libraries using bisulfite
in polyacrylamide gel electrophoresis slices with formamide denaturation
and quality control for massively parallel sequencing by oligonucleotide
ligation and detection},
journal = {Analytical Biochemistry},
year = {2009},
volume = {390},
pages = {126--135},
number = {2},
month = jul,
abstract = {Bisulfite sequencing is widely used for analysis of DNA methylation
status (i.e., 5-methylcytosine [5mC] vs. cytosine [C]) in CpG-rich
or other loci in genomic DNA (gDNA). Such methods typically involve
reaction of gDNA with bisulfite followed by polymerase chain reaction
(PCR) amplification of specific regions of interest that, overall,
converts C-->T (thymine) and 5mC-->C and then capillary sequencing
to measure C versus T composition at CpG sites. Massively parallel
sequencing by oligonucleotide ligation and detection (SOLiD) has
recently enabled relatively low-cost whole genome sequencing, and
it would be highly desirable to apply such massively parallel sequencing
to bisulfite-converted whole genomes to determine DNA methylation
status of an entire genome, which has heretofore not been reported.
As an initial step toward achieving this goal, we have extended our
ongoing interest in improving bisulfite conversion sample preparation
to include a human genome-wide fragment library for SOliD. The current
article features novel use of formamide denaturant during bisulfite
conversion of a suitably constructed library directly in a band slice
from polyacryamide gel electrophoresis (PAGE). To validate this new
protocol for 5mC-protected fragment library conversion, which we
refer to as Bis-PAGE, capillary-based size analysis and Sanger sequencing
were carried out for individual amplicons derived from single-molecule
PCR (smPCR) of randomly selected library fragments. smPCR/Capillary
Sanger sequencing of approximately 200 amplicons unambiguously demonstrated
greater than 99% C-->T conversion. All of these approximately 200
Sanger sequences were analyzed with a previously published web-accessible
bioinformatics tool (methBLAST) for mapping to human chromosomes,
the results of which indicated random distribution of analyzed fragments
across all chromosomes. Although these particular Bis-PAGE conversion
and quality control methods were exemplified in the context of a
fragment library for SOLiD, the concepts can be generalized to include
other genome-wide library constructions intended for DNA methylation
analysis by alternative high-throughput or massively parallelized
methods that are currently available.},
issn = {0003-2697},
keywords = {DNA, Fragment library, Bisulfite, Polyacrylamide gel electrophoresis,
Single-molecule PCR, Capillary electrophoresis, Sanger sequencing,
Massively parallel sequencing by oligonucleotide ligation and detection},
url = {http://www.sciencedirect.com/science/article/B6W9V-4W3HX8M-3/2/a6c9bb65f92080b2326ccc12e5fa41c0}
}
@ARTICLE{Ranade2008,
author = {Ranade, Swati S. and Yang-Zhou, Donghui and Kong, Sek Won and McDonald,
Elizabeth C. and Cook, Tiffany A. and Pignoni, Francesca},
title = {Analysis of the Otd-dependent transcriptome supports the evolutionary
conservation of CRX/OTX/OTD functions in flies and vertebrates},
journal = {Developmental Biology},
year = {2008},
volume = {315},
pages = {521--534},
number = {2},
month = mar,
abstract = {Homeobox transcription factors of the vertebrate CRX/OTX family play
critical roles in photoreceptor neurons, the rostral brain and circadian
processes. In mouse, the three related proteins, CRX, OTX1, and OTX2,
fulfill these functions. In Drosophila, the single founding member
of this gene family, called orthodenticle (otd), is required during
embryonic brain and photoreceptor neuron development. We have used
global gene expression analysis in late pupal heads to better characterize
the post-embryonic functions of Otd in Drosophila. We have identified
61 genes that are differentially expressed between wild type and
a viable eye-specific otd mutant allele. Among them, about one-third
represent potentially direct targets of Otd based on their association
with evolutionarily conserved Otd-binding sequences. The spectrum
of biological functions associated with these gene targets establishes
Otd as a critical regulator of photoreceptor morphology and phototransduction,
as well as suggests its involvement in circadian processes. Together
with the well-documented role of otd in embryonic patterning, this
evidence shows that vertebrate and fly genes contribute to analogous
biological processes, notwithstanding the significant divergence
of the underlying genetic pathways. Our findings underscore the common
evolutionary history of photoperception-based functions in vertebrates
and invertebrates and support the view that a complex nervous system
was already present in the last common ancestor of all bilateria.},
issn = {0012-1606},
keywords = {Phototransduction, Photoreceptor, Circadian rhythms, Orthodenticle,
Ocelliless, Oc, Visual transduction, Eye evolution, Photoreceptor
development},
url = {http://www.sciencedirect.com/science/article/B6WDG-4RR214N-2/2/84c2d7405a3d0e2f2a5c7810b0c272b3}
}
@BOOK{Rand2009,
title = {Methods for the Analysis of DNA Methylation},
publisher = {Wiley-VCH Verlag GmbH \& Co. KGaA},
year = {2009},
author = {Rand, Keith N. and Molloy, Peter L.},
pages = {263--276},
abstract = {Summary 10.1002/9783527626588.ch17.abs This chapter contains sections
titled:},
booktitle = {Chemoprevention of Cancer and DNA Damage by Dietary Factors},
issn = {9783527626588},
keywords = {chemoprevention, DNA, genome, methylation, 5-methyl cytosine},
url = {http://dx.doi.org/10.1002/9783527626588.ch17}
}
@ARTICLE{Rand2011,
author = {Rand, Thomas. G. and DiPenta, J. and Robbins, C. and Miller, J.D.},
title = {Effects of low molecular weight fungal compounds on inflammatory
gene transcription and expression in mouse alveolar macrophages},
journal = {Chemico-Biological Interactions},
year = {2011},
volume = {190},
pages = {139--147},
number = {2-3},
month = apr,
abstract = {The inflammatory potential and molecular mechanisms underscoring inflammatory
responses of lung cells to compounds from fungi that grow on damp
building materials is poorly understood in vitro. In this study we
evaluated the effect of pure fungal compounds on potentiating acute
inflammatory response in primary mouse alveolar macrophages (AMs)
and tested the hypothesis that AM responses to low molecular weight
fungal compounds exhibit temporal and compound specificity that mimic
that observed in the whole lung. Transcriptional responses of 13
inflammation/respiratory burst-associated genes (KC=Cxcl1, Cxcl2,
Cxcl5, Cxcl10, Ccl3, Ccl112, Ccl20, IL-1[beta], Il-6, ifi27 Tnf[alpha],
iNOS and Blvrb) were evaluated in mouse AMs exposed to a 1 ml (10-8 mol)
dose of either pure atranone C, brevianimide, cladosporin, curdlan,
LPS, neoechinulin A & B, sterigmatocystin or TMC-120A for 2 h, 4 h
and 12 h PE using customized reverse transcription (RT)-PCR based
arrays. Multianalyte ELISA was used to measure expression of 6 pro-inflammatory
cytokines common to the transcriptional assays (Cxcl1, Cxcl10, Ccl3,
IL1[beta], Ifn-[lambda] and Tnf-[alpha]) to determine whether gene
expression corresponded to the transcription data. Compared to controls,
all of these compounds induced significant (>=2.5-fold or <=-2.5-fold
change at p <= 0.05) time- and compound-specific transcriptional
gene alterations in treatment AMs. The highest number of transcribed
genes were in LPS treatment AMs at 12 h PE (12/13) followed by neoechinulin
B at 4 h PE (11/13). Highest fold change values (>30) were associated
with KC, Cxcl2, Cxcl5 and IL1[beta] genes in cells exposed to LPS.
Compound exposures also induced significant (p <= 0.05) time- and
compound-specific pro-inflammatory responses manifest as differentially
elevated Cxcl1, Cxcl10, Ccl3, Ifn-[lambda] and Tnf-[alpha] concentrations
in culture supernatant of treatment AMs. Dissimilarity in transcriptional
responses in AMs and our in vivo model of lung disease is likely
attributable to whole lung vs. isolated cell responsive and dose
differences between the two studies. The results not only indicate
that low molecular weight compounds from fungi that grow in damp
built environments are potently pro-inflammatory in vitro, it further
highlights the important role AMs play in innate lung defence, and
against exposure to low molecular weight fungal compounds. These
observations further support our position that exposure to low molecular
weight compounds from indoor-associated fungi may provoke some of
the inflammatory health effects reported from humans in damp building
environments. They also open up a hypothesis building process that
could explain the rise of non-atopic asthma associated with fungi.},
issn = {0009-2797},
keywords = {Low molecular weight fungal compounds, Mouse alveolar macrophages,
Inflammation-associated gene arrays, Multi-analyte cytokine expression},
url = {http://www.sciencedirect.com/science/article/pii/S0009279711000937}
}
@ARTICLE{Randall2008,
author = {Randall, Louise M. and Amante, Fiona H. and McSweeney, Karli A. and
Zhou, Yonghong and Stanley, Amanda C. and Haque, Ashraful and Jones,
Malcolm K. and Hill, Geoff R. and Boyle, Glen M. and Engwerda, Christian
R.},
title = {Common Strategies To Prevent and Modulate Experimental Cerebral Malaria
in Mouse Strains with Different Susceptibilities},
journal = {Infect. Immun.},
year = {2008},
volume = {76},
pages = {3312--3320},
number = {7},
month = jul,
abstract = {Cerebral malaria (CM) is a severe complication of Plasmodium falciparum
infection, predominantly experienced by children and nonimmune adults,
which results in significant mortality and long-term sequelae. Previous
studies have reported distinct susceptibility gene loci in CBA/CaH
(CBA) and C57BL/6 (B6) mice with experimental CM (ECM) caused by
infection with Plasmodium berghei ANKA. Here we present an analysis
of genome-wide expression profiles in brain tissue taken from B6
and CBA mice with ECM and report significant heterogeneity between
the two mouse strains. Upon comparison of the leukocyte composition
of ECM brain tissue, microglia were expanded in B6 mice but not CBA
mice. Furthermore, circulating levels of gamma interferon, interleukin-10,
and interleukin-6 were significantly higher in the serum of B6 mice
than in that of CBA mice with ECM. Two therapeutic strategies were
applied to B6 and CBA mice, i.e., (i) depletion of regulatory T (Treg)
cells prior to infection and (ii) depletion of CD8+ T cells after
the establishment of ECM. Despite the described differences between
susceptible mouse strains, depletion of Treg cells before infection
attenuated ECM in both B6 and CBA mice. In addition, the depletion
of CD8+ T cells when ECM symptoms are apparent leads to abrogation
of ECM in B6 mice and a lack of progression of ECM in CBA mice. These
results may have important implications for the development of effective
treatments for human CM.},
url = {http://iai.asm.org/cgi/content/abstract/76/7/3312}
}
@ARTICLE{Rane2010,
author = {Rane, Lalit and Vudattu, Nalini and Bourcier, Kasia and Graniar,
Eva and Hillert, Jan and Seyfert, Vicki and Maeurer, M J},
title = {Alternative splicing of interleukin-7 (IL-7) and interleukin-7 receptor
alpha (IL-7R[alpha]) in peripheral blood from patients with multiple
sclerosis (MS)},
journal = {Journal of Neuroimmunology},
year = {2010},
volume = {222},
pages = {82--86},
number = {1-2},
month = may,
abstract = {IL-7 and IL-7R[alpha] (IL-7R) form a non-redundant ligand receptor
system which plays a crucial role in human T cell immunity. Both
IL-7 and IL-7R are multi-exonal genes and exhibit alternative splicing.
We measured the relative distribution of IL-7 and IL-7R spliced mRNA
from patients with MS and healthy individuals and observed extensive
alternative splicing of both genes with marked differences in proportional
transcript expression levels. We report here for the first time that
the IL-7 transcript, lacking exon 4, and not the full length IL-7
represents the dominant IL-7 RNA transcript in human PBMCs and a
novel IL-7R splice variant lacking exons 5, 6 and 7.},
issn = {0165-5728},
keywords = {T-cells, MS, CD127, Interleukin-7, IL-7 receptor, Alternative splicing},
url = {http://www.sciencedirect.com/science/article/B6T03-4YK88WY-1/2/fa0bab03dfb38dde94e98f45ac9ccb3a}
}
@ARTICLE{Ranheim2008,
author = {Ranheim, Trine and Mattingsdal, Morten and Lindvall, Jessica M. and
Holla, Øystein L. and Berge, Knut Erik and Kulseth, Mari Ann and
Leren, Trond P.},
title = {Genome-wide expression analysis of cells expressing gain of function
mutant D374Y-PCSK9},
journal = {J. Cell. Physiol.},
year = {2008},
volume = {217},
pages = {459--467},
number = {2},
abstract = {Abstract 10.1002/jcp.21519.abs Proprotein convertase subtilisin/kexin
type 9 (PCSK9) is a key regulator of serum cholesterol. The possibility
that PCSK9 also functions in other pathways needs to be addressed.
We have transfected HepG2 cells with mutant D374Y-PCSK9 or control
vector. Gene expression signatures were determined using the Affymetrix
GeneChip technology, and the expression pattern of selected genes
was confirmed by quantitative real-time polymerase chain reaction
(qRT-PCR). Data was normalized and analyzed using a model-based background
adjustment for oligonucleotide expression arrays, then filtered based
upon expression within treatments group, and subjected to moderated
t-statistics. Five hundred twenty transcripts had altered expression
levels between D374Y-PCSK9 and control vector. Among the 520 probes
on our top list, 312 were found to have an assigned Gene Ontology
(GO) term, and 96 were found in the Kyoto Encyclopedia of Genes and
Genomes (KEGG) pathways. Genome-wide expression profiling revealed
that “steroid biosynthesis,� “sterol metabolism,� and “cholesterol
biosynthsis� were affected by D374Y-PCSK9. Also, the GO biological
process terms “response to stresss,� “response to virus,�
“response to unfolded protein,� and “immune response� were
influenced by D374Y-PCSK9. Our results suggest that D374Y-PCSK9 results
in up-regulation of genes involved in sterol biosynthesis and down-regulation
of stress-response genes and specific inflammation pathways. J. Cell.
Physiol. 217: 459–467, 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.21519}
}
@ARTICLE{Rantala2008,
author = {Rantala, Anne and Rizzi, Ermanno and Castiglioni, Bianca and De Bellis,
Gianluca and Sivonen, Kaarina},
title = {Identification of hepatotoxin-producing cyanobacteria by DNA-chip},
journal = {Environmental Microbiology},
year = {2008},
volume = {10},
pages = {653--664},
number = {3},
abstract = {Summary We developed a new tool to detect and identify hepatotoxin-producing
cyanobacteria of the genera Anabaena, Microcystis, Planktothrix,
Nostoc and Nodularia. Genus-specific probe pairs were designed for
the detection of the microcystin (mcyE) and nodularin synthetase
genes (ndaF) of these five genera to be used with a DNA-chip. The
method couples a ligation detection reaction, in which the polymerase
chain reaction (PCR)-amplified mcyE/ndaF genes are recognized by
the probe pairs, with a hybridization on a universal microarray.
All the probe pairs specifically detected the corresponding mcyE/ndaF
gene sequences when DNA from the microcystin- or nodularin-producing
cyanobacterial strains were used as template in the PCR. Furthermore,
the strict specificity of detection enabled identification of the
potential hepatotoxin producers. Detection of the genes was very
sensitive; only 1–5 fmol of the PCR product were needed to produce
signal intensities that exceeded the set background threshold level.
The genus-specific probe pairs also reliably detected potential microcystin
producers in DNA extracted from six lake and four brackish water
samples. In lake samples, the same microcystin producers were identified
with quantitative real-time PCR analysis. The specificity, sensitivity
and ability of the DNA-chip in simultaneously detecting all the main
hepatotoxin producers make this method suitable for high-throughput
analysis and monitoring of environmental samples.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2007.01488.x}
}
@ARTICLE{Ranucci2011,
author = {Ranucci, C. S. and Tagmyer, T. and Duncan, P.},
title = {Adventitious Agent Risk Assessment Case Study: Evaluation of RotaTeq(R)
for the Presence of Porcine Circovirus},
journal = {PDA J. Pharm. Sci. Technol.},
year = {2011},
volume = {65},
pages = {589-598},
number = {6},
abstract = {CONFERENCE PROCEEDINGProceedings of the PDA/FDA Adventitious Viruses
in Biologics: Detection and Mitigation Strategies Workshop in Bethesda,
MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda,
MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco,
CA) In June of 2010, results of metagenomic and panmicrobial microarray
analysis of a number of commercially available vaccine products were
published, identifying the unexpected presence of porcine circovirus
(PCV) in of one of the vaccine products tested. This testing did
not detect any sequences of contaminating viruses in RotaTeq(R) (rotavirus
vaccine, live, oral, pentavalent, RV5, Merck & Co., Inc., Whitehouse
Station, NJ). To confirm this finding, Merck developed and applied
a number of polymerase chain reaction-based analytical methods and
a test algorithm to systematically demonstrate the absence of infectious
PCV in RotaTeq(R). This paper will describe the methodology and rationale
developed to thoroughly assess key starting materials, product intermediates,
and final product to demonstrate the absence of infectious PCV, and
the continued quality of this product. This approach could be applied
to assess the validity of other adventitious agent risks encountered
in biological processes and products.},
doi = {10.5731/pdajpst.2011.00827},
eprint = {http://journal.pda.org/cgi/reprint/65/6/589.pdf},
url = {http://journal.pda.org/cgi/content/abstract/65/6/589}
}
@ARTICLE{Rao2012,
author = {Jagadeesh Sridhara Rao and Matthew Kellom and Edmund Arthur Reese
and Stanley Isaac Rapoport and Hyung-Wook Kim},
title = {Dysregulated glutamate and dopamine transporters in postmortem frontal
cortex from bipolar and schizophrenic patients},
journal = {Journal of Affective Disorders},
year = {2012},
volume = {136},
pages = {63 - 71},
number = {1–2},
abstract = {Background Dysregulated glutamate, serotonin and dopamine neurotransmission
has been reported in bipolar disorder (BD) and schizophrenia (SZ),
but the underlying mechanisms of dysregulation are not clear. We
hypothesized that they involve alterations in excitatory amino acid
transporters (EAATs), the serotonin reuptake transporter (SERT),
and the dopamine reuptake transporter (DAT). Methods To test this
hypothesis, we determined protein and mRNA levels of EAAT subtypes
1–4, of the SERT and of the DAT in postmortem frontal cortex from
BD (n = 10) and SZ (n = 10) patients and from
healthy control (n = 10) subjects. Results Compared to
control levels, protein and mRNA levels of EAAT1 were increased significantly
in cortex from both BD and SZ patients. EAAT2 protein and mRNA levels
were decreased significantly in BD but not in SZ cortices. EAAT3
and EAAT 4 protein and mRNA levels were significantly higher in SZ
but not in BD compared with control. DAT protein and mRNA levels
were decreased significantly in both BD and SZ cortices. There was
no significant change in SERT expression in either BD or SZ. Conclusions
The altered EAATs and DAT expression could result in altered glutamatergic
and hyperdopaminergic function in BD and SZ. Differently altered
EAATs involved in glutamatergic transmission could be therapeutic
targets for treating BD and SZ.},
doi = {10.1016/j.jad.2011.08.017},
issn = {0165-0327},
keywords = {Bipolar disorder},
url = {http://www.sciencedirect.com/science/article/pii/S0165032711004897}
}
@ARTICLE{Rao2008,
author = {Rao, Narsing A. and Saraswathy, Sindhu and Wu, Guey Shuang and Katselis,
George S. and Wawrousek, Eric F. and Bhat, Suraj},
title = {Elevated Retina-Specific Expression of the Small Heat Shock Protein,
{alpha}A-crystallin, Is Associated with Photoreceptor Protection
in Experimental Uveitis},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {1161--1171},
number = {3},
month = mar,
abstract = {PURPOSE. During the early phase of experimental autoimmune uveitis
(EAU), before macrophages infiltrate the retina and uvea, photoreceptor
mitochondrial oxidative stress, nitration of photoreceptor mitochondrial
proteins, and release of cytochrome c have been observed. However,
no apoptosis has been detected during this phase. In this study,
{alpha}A-crystallin upregulation in the retina and its antiapoptotic
protective role were evaluated in early EAU. METHODS. Gene microarrays
were first used to identify upregulated genes in retinas with early
EAU. Among highly upregulated crystallins, {alpha}A was confirmed
by real-time polymerase chain reaction and Western blot, and the
site of upregulation was localized by immunohistochemistry. The association
of {alpha}A-crystallin to nitrated cytochrome c and interaction with
a procaspase-3 subunit was assayed. Photoreceptor apoptosis in {alpha}A
knockout mice was compared with that in wild-type animals with EAU,
by using the terminal transferase dUTP nick-end labeling assay and
polymerase chain reaction. RESULTS. In early EAU, {alpha}A-crystallin
was increased 33-fold, and the site of increase was localized to
the photoreceptor inner segments. This crystallin suppressed apoptosis
by associating with the nitrated cytochrome c and p24. The association
with nitrated cytochrome c, in particular, appeared to be restricted
to nitrated cytochrome c, and thus, no association of non-nitrated
cytochrome c was detected. The knockout mice showed signs of EAU
development early and showed apoptosis in the retina; no such changes
were seen in the wild-type control animals. CONCLUSIONS. {alpha}A-Crystallin
is highly upregulated in the retina during early EAU. This upregulation
is localized primarily in the photoreceptor inner segments, the site
of mitochondrial oxidative stress. Further, in early EAU, the photoreceptors
preferentially use {alpha}A-crystallin to suppress mitochondrial
oxidative stress-mediated apoptosis.},
url = {http://www.iovs.org/cgi/content/abstract/49/3/1161}
}
@ARTICLE{Rao2008a,
author = {Rao, N. A. S. and Van Wolferen, M. E. and Van Den Ham, R. and Van
Leenen, D. and Groot Koerkamp, M. J. A. and Holstege, F. C. P. and
Mol, J. A.},
title = {cDNA microarray profiles of canine mammary tumour cell lines reveal
deregulated pathways pertaining to their phenotype},
journal = {Animal Genetics},
year = {2008},
volume = {39},
pages = {333--345},
number = {4},
abstract = {Summary Mammary cancer is the most common type of cancer in female
dogs with a lifetime risk of over 24% when dogs are not spayed. The
elucidation of the complete canine genome opens new areas for development
of cancer therapies. These should be tested first by in vitro models
such as cell lines. However, to date, no canine mammary cell lines
have been characterized by expression profiling. In this study, canine
mammary tumour cell lines with histologically distinct primary tumours
of origin were characterized using a newly developed canine cDNA
microarray. Comparisons of gene expression profiles showed enrichment
for distinct biological pathways and were related to biological properties
of the cell lines such as growth rate and in vitro tumourigenicity.
Additionally, gene expression profiles of cell lines also showed
correspondence to their tumour of origin. Major differences were
found in Wnt, cell cycle, cytokine/Rho-GTPase, alternative complement
and integrin signalling pathways. Because these pathways show an
overlap at the molecular level with those found in human breast cancer,
the expression profiling of spontaneous canine mammary cancer may
also function as a biological sieve to identify conserved gene expression
or pathway profiles of evolutionary significance that are involved
in tumourigenesis. These results are the basis for further characterization
of canine mammary carcinomas and development of new therapies directed
towards specific pathways. In addition these cell lines can be used
to further investigate identified deregulated pathways and characterize
until now unannotated genes.},
issn = {1365-2052},
keywords = {canine, cell lines, gene expression, mammary tumour, pathway},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2008.01733.x}
}
@ARTICLE{Rao2009,
author = {Rao, P. Vasantha and Maddala, Rupalatha},
title = {Abundant Expression of Ponsin, a Focal Adhesion Protein, in Lens
and Downregulation of Its Expression by Impaired Cytoskeletal Signaling},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {1769--1777},
number = {4},
month = apr,
abstract = {PURPOSE. This study was undertaken to improve understanding of the
defective lens developmental changes induced by the transgenic overexpression
of the Rho GDP dissociation inhibitor RhoGDI{alpha}. The study was
focused on a single differentially expressed gene encoding ponsin,
a cell adhesion interacting signaling adaptor protein. METHODS. Total
RNA extracted from the P7 lenses of Rho GDI{alpha} transgenic mice
was subjected to cDNA microarray analysis. Ponsin distribution in
the mouse lenses was determined by immunofluorescence and immunoblot
analyses. Interactions among ponsin, actin, and Rho GTPase signaling
pathways were explored in lens epithelial cells. RESULTS. The RhoGDI{alpha}
transgenic mouse lenses revealed a marked downregulation of expression
of multiple splice variants of ponsin. Expression of one of the ponsins
(U58883) was found to be abundant in normal mouse lenses. Although
ponsin was localized predominantly to the focal adhesions in lens
epithelial cells, it was distributed to both the epithelium and fibers,
with some isoforms being enriched primarily in the Triton X-100-insoluble
fraction in lens tissue. Further, whereas constitutively active RhoA
induced ponsin clustering at the leading edges, inhibition of Rho
kinase and latrunculin treatment were noted to lead to decreases
in ponsin protein levels in lens epithelial cells. CONCLUSIONS. Abundant
expression of ponsin, a focal adhesion protein in the lens tissue
indicates a potential role for this protein in lens fiber cell migration
and adhesion. Ponsin expression appears to be closely dependent on
Rho GTPase-regulated integrity of actin cytoskeletal organization.},
url = {http://www.iovs.org/cgi/content/abstract/50/4/1769}
}
@ARTICLE{Rao2004,
author = {Rao, Raj R. and Calhoun, John D. and Qin, Xiaoting and Rekaya, Romdhane
and Clark, Jason K. and Stice, Steven L.},
title = {Comparative transcriptional profiling of two human embryonic stem
cell lines},
journal = {Biotechnol. Bioeng.},
year = {2004},
volume = {88},
pages = {273--286},
number = {3},
abstract = {Abstract 10.1002/bit.20245.abs Human embryonic stem cells (ESCs) have
generated enormous interest due to their ability to self-renew and
produce many different cell types. In conjunction with microarray
technology, human ESCs provide a powerful tool for employing a systems-based
approach to deciphering the molecular mechanisms that control pluripotency
and early development. Recent work has focused on defining “stemness�
and pluripotency based on different experimental and analytical approaches
in both mouse and human ESCs. Using a mixed linear model statistical
approach, we report a stringent direct comparison between data sets
obtained from two human ESCs (BG01 and H1) in order to obtain a list
of genes that are enriched in ESCs. In addition, we used another
pluripotent population derived from BG01 ESCs to obtain a list of
genes that we consider important to the maintenance of pluripotency.
A total of 133 genes overlapped between the three pluripotent populations.
A majority of the 133 genes were classified under the key functional
categories of cell-cycle regulation, signaling, and regulation of
transcription. Key genes expressed were Oct4, Sox2, LeftyA, and Fgf2.
Also found to be enriched in all three populations is FLJ10713, a
gene encoding a hypothetical protein of unknown function that has
been shown in earlier studies to possess a homolog in mouse ESCs
and also to cluster tightly with Oct4 in human ESCs. Although there
were many genes unique to each pluripotent population, they shared
similarities based on functional ontologies that define pluripotency.
The significance of our studies underscores the need for direct comparison
of stem cell populations that share biological similarities using
uniform stringent analytical approaches, in order to better define
pluripotency. Our findings have important implications for the maintenance
of pluripotency and in developing directed differentiation strategies
for various regenerative applications. © 2004 Wiley Periodicals,
Inc.},
issn = {1097-0290},
keywords = {embryonic stem cells (ESCs), pluripotency, microarray, differentiation,
mixed linear model},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.20245}
}
@ARTICLE{Rao2011,
author = {Rao, Sheela and Welsh, Lyndsey and Cunningham, David and te Poele,
Robert H. and Benson, Martin and Norman, Andrew and Saffery, Claire
and Giddings, Ian and Workman, Paul and Clarke, Paul A.},
title = {Correlation of Overall Survival With Gene Expression Profiles in
a Prospective Study of Resectable Esophageal Cancer},
journal = {Clin Colorectal Cancer},
year = {2011},
volume = {10},
pages = {48--56},
number = {1},
month = mar,
abstract = {Purpose: Preoperative chemotherapy has demonstrated a survival benefit
for patients with potentially resectable esophageal cancer; however,
currently it is not possible to predict the benefit of this treatment
for an individual patient. This prospective study was designed to
correlate gene expression profiles with clinical outcome in this
setting. Eligible patients were deemed to have resectable disease
after staging by computed tomography, endoscopic ultrasound, and
laparoscopy as indicated and following discussion at the multidisciplinary
team meeting. All patients received neoadjuvant platinum and fluoropyrimidine-based
chemotherapy; and clinical data were entered prospectively onto a
study-specific database. Total RNA was isolated from pretreatment
tumor biopsies obtained at baseline endoscopy and analyzed using
a cDNA array consisting of 22,000 cDNA clones. Of the patients with
adequate follow-up accrued between 2002 and 2005, 35 satisfied the
quality control measures for the microarray profiling. Median follow-up
was 938 days. Supervised hierarchical clustering of normalized data
revealed 165 significantly differentially expressed genes based on
overall survival (OS; P < .01) with 2 distinct clusters: a poor outcome
group: N = 17 (1 year OS 46.2%) and a good outcome group: N = 18
(1 year OS 100%). Genes identified included those previously associated
with esophageal cancer and, interestingly, a group of genes encoding
proteins involved in the regulation of the TOLL receptor-signaling
pathway. This initial study has highlighted groups of tumors with
distinct gene expression profiles based on survival and warrants
further validation in a larger cohort. This approach may further
our understanding of individual tumor biology and thus facilitate
the development of tailored treatment.},
issn = {1533-0028},
keywords = {Endoscopic ultrasound, Esophageal cancer, Gene expression profiling,
RT-PCR, Treatment},
publisher = {Cancer Information Group,},
refid = {S1533-0028(11)70063-9},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1533002811700639?showall=true}
}
@ARTICLE{Rao2010,
author = {Rao, Shailaja K. and Pavicevic, Zoran and Du, Ziyun and Kim, Jong-Gwan
and Fan, Meiyun and Jiao, Yan and Rosebush, Molly and Samant, Sandeep
and Gu, Weikuan and Pfeffer, Lawrence M. and Nosrat, Christopher
A.},
title = {Pro-inflammatory Genes as Biomarkers and Therapeutic Targets in Oral
Squamous Cell Carcinoma},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {32512--32521},
number = {42},
month = oct,
abstract = {Oral squamous cell carcinoma (OSCC) is a major health problem worldwide,
and patients have a particularly poor 5-year survival rate. Thus,
identification of the molecular targets in OSCC and subsequent innovative
therapies are greatly needed. Prolonged exposure to alcohol, tobacco,
and pathogenic agents are known risk factors and have suggested that
chronic inflammation may represent a potential common denominator
in the development of OSCC. Microarray analysis of gene expression
in OSCC cell lines with high basal NF-{kappa}B activity and OSCC
patient samples identified dysregulation of many genes involved in
inflammation, wound healing, angiogenesis, and growth regulation.
In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated
in OSCC. Moreover, IL-8 protein levels were significantly higher
in OSCC cell lines as compared with normal human oral keratinocytes.
Targeting IL-8 expression by siRNA significantly reduced the survival
of OSCC cells, indicating that it plays an important role in OSCC
development and/or progression. Inhibiting the inflammatory pathway
by aspirin and the proteasome/NF-{kappa}B pathway by bortezomib resulted
in marked reduction in cell viability in OSCC lines. Taken together
our studies indicate a strong link between inflammation and OSCC
development and reveal IL-8 as a potential mediator. Treatment based
on prevention of general inflammation and/or the NF-{kappa}B pathway
shows promise in OSCCs.},
url = {http://www.jbc.org/cgi/content/abstract/285/42/32512}
}
@ARTICLE{Raouf2008,
author = {Raouf, Afshin and Zhao, Yun and To, Karen and Stingl, John and Delaney,
Allen and Barbara, Mary and Iscove, Norman and Jones, Steven and
McKinney, Steven and Emerman, Joanne and Aparicio, Samuel and Marra,
Marco and Eaves, Connie},
title = {Transcriptome Analysis of the Normal Human Mammary Cell Commitment
and Differentiation Process},
journal = {Cell Stem Cell},
year = {2008},
volume = {3},
pages = {109--118},
number = {1},
month = jul,
abstract = {Summary Mature mammary epithelial cells are generated from undifferentiated
precursors through a hierarchical process, but the molecular mechanisms
involved, particularly in the human mammary gland, are poorly understood.
To address this issue, we isolated highly purified subpopulations
of primitive bipotent and committed luminal progenitor cells as well
as mature luminal and myoepithelial cells from normal human mammary
tissue and compared their transcriptomes obtained using three different
methods. Elements unique to each subset of mammary cells were identified,
and changes that accompany their differentiation in vivo were shown
to be recapitulated in vitro. These include a stage-specific change
in NOTCH pathway gene expression during the commitment of bipotent
progenitors to the luminal lineage. Functional studies further showed
NOTCH3 signaling to be critical for this differentiation event to
occur in vitro. Taken together, these findings provide an initial
foundation for future delineation of mechanisms that perturb primitive
human mammary cell growth and differentiation.},
issn = {1934-5909},
keywords = {STEMCELL},
url = {http://www.sciencedirect.com/science/article/B8G3V-4SWNHJ1-K/2/40bd479ff7e8276c2e27e11f876a7096}
}
@ARTICLE{Raponi2007,
author = {Raponi, Mitch and Harousseau, Jean-Luc and Lancet, Jeffrey E. and
Lowenberg, Bob and Stone, Richard and Zhang, Yi and Rackoff, Wayne
and Wang, Yixin and Atkins, David},
title = {Identification of Molecular Predictors of Response in a Study of
Tipifarnib Treatment in Relapsed and Refractory Acute Myelogenous
Leukemia},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {2254--2260},
number = {7},
month = apr,
abstract = {Purpose: Microarray technology was used to identify gene expression
markers that predict response to the orally available farnesyltransferase
inhibitor tipifarnib (Zarnestra, R115777) in acute myelogenous leukemia
(AML). Experimental Design: Gene expression profiles from 58 bone
marrow samples from a cohort of relapsed and refractory AML patients
were analyzed on the Affymetrix U133A gene chip that contains [~]22,000
genes. Results: Supervised statistical analysis identified eight
gene expression markers that could predict patient response to tipifarnib.
The most robust gene was the lymphoid blast crisis oncogene (AKAP13),
which predicted response with an overall accuracy of 63%. This gene
provided a negative predictive value of 93% and a positive predictive
value of 31% (increased from 18%). AKAP13 was overexpressed in patients
who were resistant to tipifarnib. When overexpressed in the HL60
and THP1 cell lines, AKAP13 increased the resistance to tipifarnib
by approximately 5- to 7-fold. Conclusion: Diagnostic gene expression
signatures may be used to select a group of AML patients that might
respond to tipifarnib.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/7/2254}
}
@ARTICLE{Raponi2008,
author = {Raponi, Mitch and Lancet, Jeffrey E. and Fan, Hongtao and Dossey,
Lesley and Lee, Grace and Gojo, Ivana and Feldman, Eric J. and Gotlib,
Jason and Morris, Lawrence E. and Greenberg, Peter L. and Wright,
John J. and Harousseau, Jean-Luc and Lowenberg, Bob and Stone, Richard
M. and De Porre, Peter and Wang, Yixin and Karp, Judith E.},
title = {A 2-gene classifier for predicting response to the farnesyltransferase
inhibitor tipifarnib in acute myeloid leukemia},
journal = {Blood},
year = {2008},
volume = {111},
pages = {2589--2596},
number = {5},
month = mar,
abstract = {At present, there is no method available to predict response to farnesyltransferase
inhibitors (FTIs). We analyzed gene expression profiles from the
bone marrow of patients from a phase 2 study of the FTI tipifarnib
in older adults with previously untreated acute myeloid leukemia
(AML). The RASGRP1/APTX gene expression ratio was found to predict
response to tipifarnib with the greatest accuracy using a "leave
one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide
exchange factor that activates RAS, while APTX (aprataxin) is involved
in DNA excision repair. The utility of this classifier for predicting
response to tipifarnib was validated in an independent set of 58
samples from relapsed or refractory AML, with a negative predictive
value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively
(odds ratio of 4.4). The classifier also predicted for improved overall
survival (154 vs 56 days; P < .001), which was independent of other
covariates, including a previously described prognostic gene expression
classifier. Therefore, these data indicate that a 2-gene expression
assay may have utility in categorizing a population of patients with
AML who are more likely to respond to tipifarnib.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/5/2589}
}
@ARTICLE{Raponi2006,
author = {Raponi, Mitch and Zhang, Yi and Yu, Jack and Chen, Guoan and Lee,
Grace and Taylor, Jeremy M.G. and MacDonald, James and Thomas, Dafydd
and Moskaluk, Christopher and Wang, Yixin and Beer, David G.},
title = {Gene Expression Signatures for Predicting Prognosis of Squamous Cell
and Adenocarcinomas of the Lung},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {7466--7472},
number = {15},
month = aug,
abstract = {Non-small-cell lung cancers (NSCLC) compose 80% of all lung carcinomas
with squamous cell carcinomas (SCC) and adenocarcinoma representing
the majority of these tumors. Although patients with early-stage
NSCLC typically have a better outcome, 35% to 50% will relapse within
5 years after surgical treatment. We have profiled primary squamous
cell lung carcinomas from 129 patients using Affymetrix U133A gene
chips. Unsupervised analysis revealed two clusters of SCC that had
no correlation with tumor stage but had significantly different overall
patient survival (P = 0.036). The high-risk cluster was most significantly
associated with down-regulation of epidermal development genes. Cox
proportional hazard models identified an optimal set of 50 prognostic
mRNA transcripts using a 5-fold cross-validation procedure. Quantitative
reverse transcription-PCR and immunohistochemistry using tissue microarrays
were used to validate individual gene candidates. This signature
was tested in an independent set of 36 SCC samples and achieved 84%
specificity and 41% sensitivity with an overall predictive accuracy
of 68%. Kaplan-Meier analysis showed clear stratification of high-risk
and low-risk patients [log-rank P = 0.04; hazard ratio (HR), 2.66;
95% confidence interval (95% CI), 1.01-7.05]. Finally, we combined
the SCC classifier with our previously identified adenocarcinoma
prognostic signature and showed that the combined classifier had
a predictive accuracy of 71% in 72 NSCLC samples also showing significant
differences in overall survival (log-rank P = 0.0002; HR, 3.54; 95%
CI, 1.74-7.19). This prognostic signature could be used to identify
patients with early-stage high-risk NSCLC who might benefit from
adjuvant therapy following surgery. (Cancer Res 2006; 66(15): 7466-72)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/15/7466}
}
@ARTICLE{Raposo2010,
author = {Raposo, Bruno R. and Rodrigues-Santos, Paulo and Carvalheiro, Helena
and �gua-Doce, Ana M. and Carvalho, Lina and Pereira da Silva, José
A. and Graça, Luis and Souto-Carneiro, M. Margarida},
title = {Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN
mouse model of spontaneous chronic polyarthritis},
journal = {Arthritis \& Rheumatism},
year = {2010},
volume = {62},
pages = {2953--2962},
number = {10},
abstract = {Abstract Objective CD8+ T cells are part of the T cell pool infiltrating
the synovium in rheumatoid arthritis (RA). However, their role in
the pathogenesis of RA has not been fully delineated. Using the K/BxN
mouse model of spontaneous chronic arthritis, which shares many similarities
with RA, we studied the potential of CD8+ T cell depletion with monoclonal
antibodies (mAb) to stop and reverse the progression of experimental
arthritis. Methods CD8+ T cells from the blood and articular infiltrate
of K/BxN mice were characterized for cell surface phenotypic markers
and for cytokine production. Additionally, mice were treated with
specific anti-CD8 mAb (YTS105 and YTS169.4), with and without thymectomy.
Results CD8+ T cells from the peripheral blood and joints of K/BxN
mice were mainly CD69+ and CD62L−CD27+ T cells expressing proinflammatory
cytokines (interferon-γ [IFNγ], tumor necrosis factor α [TNFα],
interleukin-17a [IL-17A], and IL-4), and granzyme B. In mice receiving
anti-CD8 mAb, the arthritis score improved 5 days after treatment.
Recovery of the CD8+ T cells was associated with a new increase in
the arthritis score after 20 days. In thymectomized and anti-CD8
mAb–treated mice, the arthritis score improved permanently. Histologic
analysis showed an absence of inflammatory infiltrate in the anti-CD8
mAb–treated mice. In anti-CD8 mAb–treated mice, the serologic
levels of TNFα, IFNγ, IL-6, and IL-5 normalized. The levels of
the disease-related anti–glucose-6-phosphate isomerase antibodies
did not change. Conclusion These results indicate that synovial activated
effector CD8+ T cells locally synthesize proinflammatory cytokines
(IFNγ, TNFα, IL-17, IL-6) and granzyme B in the arthritic joint,
thus playing a pivotal role in maintaining chronic synovitis in the
K/BxN mouse model of arthritis.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.27729}
}
@ARTICLE{Rapp2010,
author = {Rapp, Ryan and Haigler, Candace and Flagel, Lex and Hovav, Ran and
Udall, Joshua and Wendel, Jonathan},
title = {Gene expression in developing fibres of Upland cotton (Gossypium
hirsutum L.) was massively altered by domestication},
journal = {BMC Biology},
year = {2010},
volume = {8},
pages = {139},
number = {1},
abstract = {BACKGROUND:Understanding the evolutionary genetics of modern crop
phenotypes has a dual relevance to evolutionary biology and crop
improvement. Modern upland cotton (Gossypium hirsutum L.) was developed
following thousands of years of artificial selection from a wild
form, G. hirsutum var. yucatanense, which bears a shorter, sparser,
layer of single-celled, ovular trichomes ('fibre'). In order to gain
an insight into the nature of the developmental genetic transformations
that accompanied domestication and crop improvement, we studied the
transcriptomes of cotton fibres from wild and domesticated accessions
over a developmental time course.RESULTS:Fibre cells were harvested
between 2 and 25 days post-anthesis and encompassed the primary and
secondary wall synthesis stages. Using amplified messenger RNA and
a custom microarray platform designed to interrogate expression for
40,430 genes, we determined global patterns of expression during
fibre development. The fibre transcriptome of domesticated cotton
is far more dynamic than that of wild cotton, with over twice as
many genes being differentially expressed during development (12,626
versus 5273). Remarkably, a total of 9465 genes were diagnosed as
differentially expressed between wild and domesticated fibres when
summed across five key developmental time points. Human selection
during the initial domestication and subsequent crop improvement
has resulted in a biased upregulation of components of the transcriptional
network that are important for agronomically advanced fibre, especially
in the early stages of development. About 15% of the differentially
expressed genes in wild versus domesticated cotton fibre have no
homology to the genes in databases.CONCLUSIONS:We show that artificial
selection during crop domestication can radically alter the transcriptional
developmental network of even a single-celled structure, affecting
nearly a quarter of the genes in the genome. Gene expression during
fibre development within accessions and expression alteration arising
from evolutionary change appears to be 'modular' - complex genic
networks have been simultaneously and similarly transformed, in a
coordinated fashion, as a consequence of human-mediated selection.
These results highlight the complex alteration of the global gene
expression machinery that resulted from human selection for a longer,
stronger and finer fibre, as well as other aspects of fibre physiology
that were not consciously selected. We illustrate how the data can
be mined for genes that were unwittingly targeted by aboriginal and/or
modern domesticators during crop improvement and/or which potentially
control the improved qualities of domesticated cotton fibre.See Commentary:
http://www.biomedcentral.com/1741-7007/8/137},
doi = {10.1186/1741-7007-8-139},
issn = {1741-7007},
pubmedid = {21078138},
url = {http://www.biomedcentral.com/1741-7007/8/139}
}
@ARTICLE{Rapp2009,
author = {Rapp, Ryan and Udall, Joshua and Wendel, Jonathan},
title = {Genomic expression dominance in allopolyploids},
journal = {BMC Biology},
year = {2009},
volume = {7},
pages = {18},
number = {1},
abstract = {BACKGROUND:Allopolyploid speciation requires rapid evolutionary reconciliation
of two diverged genomes and gene regulatory networks. Here we describe
global patterns of gene expression accompanying genomic merger and
doubling in inter-specific crosses in the cotton genus (Gossypium
L.).RESULTS:Employing a micro-array platform designed against 40,430
unigenes, we assayed gene expression in two sets of parental diploids
and their colchicine-doubled allopolyploid derivatives. Up to half
of all genes were differentially expressed among diploids, a striking
level of expression evolution among congeners. In the allopolyploids,
most genes were expressed at mid-parent levels, but this was achieved
via a phenomenon of genome-wide expression dominance, whereby gene
expression was either up- or down-regulated to the level of one of
the two parents, independent of the magnitude of gene expression.
This massive expression dominance was approximately equal with respect
to direction (up- or down-regulation), and the same diploid parent
could be either the dominant or the recessive genome depending on
the specific genomic combination. Transgressive up- and down-regulation
were also common in the allopolyploids, both for genes equivalently
or differentially expressed between the parents.CONCLUSION:Our data
provide novel insights into the architecture of gene expression in
the allopolyploid nucleus, raise questions regarding the responsible
underlying mechanisms of genome dominance, and provide clues into
the enigma of the evolutionary prevalence of allopolyploids.},
doi = {10.1186/1741-7007-7-18},
issn = {1741-7007},
pubmedid = {19409075},
url = {http://www.biomedcentral.com/1741-7007/7/18}
}
@ARTICLE{Rasaiyaah2009,
author = {Rasaiyaah, Jane and Noursadeghi, Mahdad and Kellam, Paul and Chain,
Benjamin},
title = {Transcriptional and functional defects of dendritic cells derived
from the MUTZ-3 leukaemia line},
journal = {Immunology},
year = {2009},
volume = {127},
pages = {429--441},
number = {3},
abstract = {Summary Dendritic cells (DC) generated from MUTZ-3, an immortalized
acute myeloid leukaemia-derived cell line, have potential application
as a model for the study of human DC, and as a tool with which to
stimulate immunotherapeutic responses to cancer. However, the relationship
of MUTZ-3 DC to their non-transformed counterparts remains incompletely
understood. Immunoselected CD14+ MUTZ-3 cells were used to generate
a homogeneous population of DC (M3DC). These cells had a cell surface
phentoype and morphology characteristic of conventional monocyte-derived
DC (MDDC). Whole genome transcriptome comparison of M3DC and MDDC
however, revealed extensive differences between these two cell types.
Functional ontology-based data analysis revealed three enriched clusters
of genes downregulated in M3DC, with functions in pathogen recognition,
DC maturation and cytokine/chemokine signalling. Downregulation of
protein expression was confirmed for several of these genes. The
molecular differences were accompanied by a profoundly impaired phenotypic
and functional response of M3DC to microbial stimulation. The immortalized
phenotype of MUTZ-3 therefore reflects not only deregulated proliferative
capacity, but substantial perturbation of normal antigen-presenting
cell function. These results have important implications for studies
using MUTZ-3 as a model of MDDC or for cancer immunotherapy.},
issn = {1365-2567},
keywords = {acute myeloid leukaemia, antigen presentation, dendritic cells, tumour
immunity},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2008.03018.x}
}
@ARTICLE{Raschzok2011,
author = {Raschzok, Nathanael and Werner, Wiebke and Sallmon, Hannes and Billecke,
Nils and Dame, Christof and Neuhaus, Peter and Sauer, Igor M.},
title = {Temporal expression profiles indicate a primary function for microRNA
during the peak of DNA replication after rat partial hepatectomy},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {300},
pages = {R1363-1372},
number = {6},
abstract = {The liver has the unique capacity to regenerate after surgical resection.
However, the regulation of liver regeneration is not completely understood.
Recent reports indicate an essential role for small noncoding microRNAs
(miRNAs) in the regulation of hepatic development, carcinogenesis,
and early regeneration. We hypothesized that miRNAs are critically
involved in all phases of liver regeneration after partial hepatectomy.
We performed miRNA microarray analyses after 70% partial hepatectomy
in rats under isoflurane anesthesia at different time points (0 h
to 5 days) and after sham laparotomy. Putative targets of differentially
expressed miRNAs were determined using a bioinformatic approach.
Two-dimensional (2D)-PAGE proteomic analyses and protein identification
were performed on specimens at 0 and 24 h after resection. The temporal
dynamics of liver regeneration were characterized by 5-bromo- 2-deoxyuridine,
proliferating cell nuclear antigen, IL-6, and hepatocyte growth factor.
We demonstrate that miRNA expression patterns changed during liver
regeneration and that these changes were most evident during the
peak of DNA replication at 24 h after resection. Expression of 13
miRNAs was significantly reduced 12-48 h after resection (>25% change),
out of which downreguation was confirmed in isolated hepatocytes
for 6 miRNAs at 24 h, whereas three miRNAs were significantly upregulated.
Proteomic analysis revealed 65 upregulated proteins; among them,
23 represent putative targets of the differentially expressed miRNAs.
We provide a temporal miRNA expression and proteomic dataset of the
regenerating rat liver, which indicates a primary function for miRNA
during the peak of DNA replication. These data will assist further
functional studies on the role of miRNAs during liver regeneration.},
doi = {10.1152/ajpregu.00632.2010},
eprint = {http://ajpregu.physiology.org/cgi/reprint/300/6/R1363.pdf},
url = {http://ajpregu.physiology.org/cgi/content/abstract/300/6/R1363}
}
@ARTICLE{Raslova2007,
author = {Raslova, Hana and Kauffmann, Audrey and Sekkai, Dalila and Ripoche,
Hugues and Larbret, Frederic and Robert, Thomas and Le Roux, Diana
Tronik and Kroemer, Guido and Debili, Najet and Dessen, Philippe
and Lazar, Vladimir and Vainchenker, William},
title = {Interrelation between polyploidization and megakaryocyte differentiation:
a gene profiling approach},
journal = {Blood},
year = {2007},
volume = {109},
pages = {3225--3234},
number = {8},
month = apr,
abstract = {Polyploidization is a part of the normal developmental process leading
to platelet production during megakaryocyte (MK) differentiation.
Ploidization is mainly involved in cell enlargement, but it is not
clear whether gene expression is modified during MK ploidization.
In this study, human MKs were grown from CD34+ cells in the presence
of thrombopoietin and sorted according to their ploidy level. A pangenomic
microarray technique was applied to compare gene expression in 2N-,
4N-, 8N-, and 16N-sorted MKs. Using hierarchical clustering, we demonstrated
that 2N and 4N MKs or 8N and 16N MKs are 2 different close populations
with 105 discriminating genes. In the second approach, we determined
the profile of genes that were continuously down- and up-regulated
during polyploidization. Among the 100 down-regulated genes, 24 corresponded
to genes involved in DNA replication and repair. The great majority
of up-regulated genes corresponded to genes directly involved in
platelet functions, such as genes encoding specific platelet glycoproteins
and {alpha}-granule proteins, actin and microtubule cytoskeleton,
factors involved in signaling, and transport proteins. Together,
these results suggest that MK polyploidization per se does not regulate
gene expression but is intrinsically included in the differentiation
process.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/8/3225}
}
@ARTICLE{Rasmussen2010,
author = {Rasmussen, Louise Maymann and Frederiksen, Klaus Stensgaard and Din,
Nanni and Galsgaard, Elisabeth and Christensen, Leif and Berchtold,
Martin Werner and Panina, Svetlana},
title = {Prolactin and oestrogen synergistically regulate gene expression
and proliferation of breast cancer cells},
journal = {Endocr. Relat. Cancer},
year = {2010},
volume = {17},
pages = {809--822},
number = {3},
month = aug,
abstract = {The pituitary hormone prolactin (PRL) plays an important role in mammary
gland development. It was also suggested to contribute to breast
cancer progression. In vivo data strongly supported a crucial role
of PRL in promoting tumour growth; however, PRL demonstrated only
a weak, if any, pro-proliferative effect on cancer cells in vitro.
Several recent studies indicated that PRL action in vivo may be influenced
by the hormonal milieu, e.g. other growth factors such as 17{beta}-oestradiol
(E2). Here, we explored the potential interplay between PRL and E2
in regulation of gene expression and cell growth. PRL alone induced
either a weak or no proliferative response of T47D and BT-483 cells
respectively, while it drastically enhanced cell proliferation in
E2-stimulated cultures. Affymetrix microarray analysis revealed 12
genes to be regulated by E2, while 57 genes were regulated by PRL
in T47D cells. Most of the PRL-regulated genes (42/57) were not previously
described as PRL target genes, e.g. WT1 and IER3. One hundred and
five genes were found to be regulated upon PRL/E2 co-treatment: highest
up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3,
SOCS3, WT1 and AREG. PRL and E2 synergised to regulate EGR3, while
multiple genes were regulated additively. These data show a novel
interplay between PRL and E2 to modulate gene regulation in breast
cancer cells.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/17/3/809}
}
@ARTICLE{Rasmussen2008,
author = {Rasmussen, Rosalee S. and Morrissey, Michael T.},
title = {DNA-Based Methods for the Identification of Commercial Fish and Seafood
Species},
journal = {Comprehensive Reviews in Food Science and Food Safety},
year = {2008},
volume = {7},
pages = {280--295},
number = {3},
abstract = {ABSTRACT:  The detection of species substitution has become an important
topic within the food industry and there is a growing need for rapid,
reliable, and reproducible tests to verify species in commercial
fish and seafood products. Increases in international trade and global
seafood consumption, along with fluctuations in the supply and demand
of different fish and seafood species, have resulted in intentional
product mislabeling. The effects of species substitution are far-reaching
and include economic fraud, health hazards, and illegal trade of
protected species. To improve detection of commercial seafood fraud,
a variety of DNA-based techniques have been developed, including
Multiplex PCR, FINS, PCR-RFLP, PCR-RAPD, PCR-AFLP, and PCR-SSCP,
which are all based on polymorphisms in the genetic codes of different
species. These techniques have been applied in the differentiation
of many types of fish and seafood species, such as gadoids, salmonids,
scombroids, and bivalves. Some emerging technologies in this field
include the use of real-time PCR, lab-on-a-chip, and DNA microarray
chips. In this review article, the major DNA-based methods currently
employed in the authentication of commercial fish and seafood species
are discussed and future trends are highlighted. Examples of commercial
applications and the use of online database resources are also considered.},
issn = {1541-4337},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1541-4337.2008.00046.x}
}
@ARTICLE{Raso2011a,
author = {Raso, Alessandro and Mascelli, Samantha and Biassoni, Roberto and
Nozza, Paolo and Kool, Marcel and Pistorio, Angela and Ugolotti,
Elisabetta and Milanaccio, Claudia and Pignatelli, Sara and Ferraro,
Manuela and Pavanello, Marco and Ravegnani, Marcello and Cama, Armando
and Garre, Maria Luisa and Capra, Valeria},
title = {High levels of PROM1 (CD133) transcript are a potential predictor
of poor prognosis in medulloblastoma},
journal = {Neuro Oncology},
year = {2011},
volume = {13},
pages = {500--508},
number = {5},
month = may,
abstract = {The surface marker PROM1 is considered one of the most important markers
of tumor-initiating cells, and its expression is believed to be an
adverse prognostic factor in gliomas and in other malignancies. To
date, to our knowledge, no specific studies of its expression in
medulloblastoma series have been performed. The aims of our study
were to evaluate the expression profile of the PROM1 gene in medulloblastoma
and to assess its possible role as a prognostic factor. The PROM1
gene expression was evaluated by quantitative- polymerase chain reaction
on 45 medulloblastoma samples by using specific dye-labeled probe
systems. A significantly higher expression of PROM1 was found both
in patients with poorer prognosis (P= .007) and in those with metastasis
(P= .03). Kaplan-Meier analysis showed that both overall survival
(OS) and progression-free survival (PFS) were shorter in patients
with higher PROM1 mRNA levels than in patients with lower expression,
even when the desmoplastic cases were excluded (P= .0004 and P= .002,
for OS and PFS for all cases, respectively; P= .002 and P= .008 for
OS and PFS for nondesmoplastic cases, respectively). Cox regression
model demonstrated that PROM1 expression is an independent prognostic
factor (hazard ratio, 4.56; P= .008). The result was validated on
an independent cohort of 42 cases by microarray-based analysis (P=
.019). This work suggests that high mRNA levels of PROM1 are associated
with poor outcome in pediatric medulloblastoma. Furthermore, high
PROM1 expression levels seem to increase the likelihood of metastases.
Such results need to be confirmed in larger prospective series to
possibly incorporate PROM1 gene expression into risk classification
systems to be used in the clinical setting.},
comment = {10.1093/neuonc/nor022},
url = {http://neuro-oncology.oxfordjournals.org/cgi/content/abstract/13/5/500}
}
@ARTICLE{Raso2011,
author = {Raso, Alessandro and Mascelli, Samantha and Nozza, Paolo and Ugolotti,
Elisabetta and Vanni, Irene and Capra, Valeria and Biassoni, Roberto},
title = {Troubleshooting fine-tuning procedures for qPCR system design},
journal = {Journal of Clinical Laboratory Analysis},
year = {2011},
volume = {25},
pages = {389--394},
number = {6},
abstract = {Quantitative real-time PCR (qPCR) has been improved and optimized
over the past decade for a wide range of applications. Design of
primers and probes is one of the crucial steps to obtain high system
efficiency of qPCR since design pitfalls influence negatively amplification
performances. We report the results of some experiments. First, we
demonstrate the utility of optimal primer design and concentration
in PCR by constructing suboptimal primers, for instance with hairpin
and primer–dimers secondarystructures, and quantifying the decrease
in efficiency of amplification. Second, we show the adverse effects
of the target sequence harboring stable secondary structures on the
primer binding sites. Finally, we let see that the mere use of probe-based
detection is not enough to ensure robustness of qPCR data, because
the eventual detrimental products generated by primers not well designed
may influence in any case the PCR efficiency. J. Clin. Lab. Anal.
25:389–394, 2011. © 2011 Wiley Periodicals, Inc.},
doi = {10.1002/jcla.20489},
issn = {1098-2825},
keywords = {qPCR, RT-qPCR, primers design, qPCR systems design, SYBR detection},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcla.20489}
}
@ARTICLE{Rasooly2005,
author = {Rasooly, Reuven and Schuster, Gertrud U. and Gregg, Jeffrey P. and
Xiao, Jia-Hao and Chandraratna, Roshantha A. S. and Stephensen, Charles
B.},
title = {Retinoid X Receptor Agonists Increase Bcl2a1 Expression and Decrease
Apoptosis of Naive T Lymphocytes},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {7916--7929},
number = {12},
month = dec,
abstract = {Vitamin A affects many aspects of T lymphocyte development and function.
The vitamin A metabolites all-trans- and 9-cis-retinoic acid regulate
gene expression by binding to the retinoic acid receptor (RAR), while
9-cis-retinoic acid also binds to the retinoid X receptor (RXR).
Naive DO11.10 T lymphocytes expressed mRNA and protein for RAR-{alpha},
RXR-{alpha}, and RXR-{beta}. DNA microarray analysis was used to
identify RXR-responsive genes in naive DO11.10 T lymphocytes treated
with the RXR agonist AGN194204. A total of 128 genes was differentially
expressed, including 16 (15%) involved in cell growth or apoptosis.
Among these was Bcl2a1, an antiapoptotic Bcl2 family member. Quantitative
real-time PCR analysis confirmed this finding and demonstrated that
Bcl2a1 mRNA expression was significantly greater in nonapoptotic
than in apoptotic T lymphocytes. The RXR agonist 9-cis-retinoic acid
also increased Bcl2a1 expression, although all-trans-retinoic acid
and ligands for other RXR partner receptors did not. Treatment with
AGN194204 and 9-cis-retinoic acid significantly decreased apoptosis
measured by annexin V staining but did not affect expression of Bcl2
and Bcl-xL. Bcl2a1 promoter activity was examined using a luciferase
promoter construct. Both AGN194204 and 9-cis-retinoic acid significantly
increased luciferase activity. In summary, these data demonstrate
that RXR agonists increase Bcl2a1 promoter activity and increase
expression of Bcl2a1 in naive T lymphocytes but do not affect Bcl2
and Bcl-xL expression in naive T lymphocytes. Thus, this effect on
Bcl2a1 expression may account for the decreased apoptosis seen in
naive T lymphocytes treated with RXR agonists.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/12/7916}
}
@ARTICLE{Rasouli2009,
author = {Rasouli, Neda and Yao-Borengasser, Aiwei and Varma, Vijayalakshmi
and Spencer, Horace J. and McGehee, Robert E., Jr and Peterson, Charlotte
A. and Mehta, Jawahar L. and Kern, Philip A.},
title = {Association of Scavenger Receptors in Adipose Tissue With Insulin
Resistance in Nondiabetic Humans},
journal = {Arterioscler Thromb Vasc Biol},
year = {2009},
volume = {29},
pages = {1328--1335},
number = {9},
month = sep,
abstract = {Objective-- Scavenger receptors play crucial roles in the pathogenesis
of atherosclerosis, but their role in insulin resistance has not
been explored. We hypothesized that scavenger receptors are present
in human adipose tissue resident macrophages, and their gene expression
is regulated by adiponectin and thaizolidinediones. Methods and Results--
The gene expression of scavenger receptors including scavenger receptor-A
(SRA), CD36, and lectin-like oxidized LDL receptor-1 (LOX-1) were
studied in subcutaneous adipose tissue of nondiabetic subjects and
in vitro. Adipose tissue SRA expression was independently associated
with insulin resistance. Pioglitazone downregulated SRA gene expression
in adipose tissue of subjects with impaired glucose tolerance and
decreased LOX-1 mRNA in vitro. Macrophage LOX-1 expression was decreased
when macrophages were cocultured with adipocytes or when exposed
to adipocyte conditioned medium. Adding adiponectin neutralizing
antibody resulted in a 2-fold increase in LOX-1 gene expression demonstrating
that adiponectin regulates LOX-1 expression. Conclusion-- Adipose
tissue scavenger receptors are strongly associated with insulin resistance.
Pioglitazone and adiponectin regulate gene expression of SRA and
LOX-1, and this may have clinical implications in arresting the untoward
sequalae of insulin resistance and diabetes, including accelerated
atherosclerosis. The relationship between scavenger receptors and
insulin resistance is not well understood. We demonstrated that adipose
tissue scavenger receptors are strongly associated with insulin resistance
in nondiabetic subjects. Pioglitazone and adiponectin regulated the
expression of scavenger receptor A and lectin-like oxidized LDL,
and this may have important clinical implications.},
url = {http://atvb.ahajournals.org/cgi/content/abstract/29/9/1328}
}
@ARTICLE{Rastaldi2006,
author = {Rastaldi, Maria Pia and Armelloni, Silvia and Berra, Silvia and Calvaresi,
Novella and Corbelli, Alessandro and Giardino, Laura Anna and Li,
Min and Wang, Guo Quin and Fornasieri, Alessandro and Villa, Antonello
and Heikkila, Eija and Soliymani, Rabah and Boucherot, Anissa and
Cohen, Clemens David and Kretzler, Matthias and Nitsche, Almut and
Ripamonti, Maddalena and Malgaroli, Antonio and Pesaresi, Marzia
and Forloni, Gian Luigi and Schlondorff, Detlef and Holthofer, Harry
and D'Amico, Giuseppe},
title = {Glomerular podocytes contain neuron-like functional synaptic vesicles},
journal = {FASEB J},
year = {2006},
volume = {20},
pages = {976--978},
number = {7},
month = may,
abstract = {Although patients with chronic renal failure are increasing worldwide,
many aspects of kidney biology remain to be elucidated. Recent research
has uncovered several molecular properties of the glomerular filtration
barrier, in which podocytes, highly differentiated, ramified cells
that enwrap the glomerular basement membrane, have been reported
to be mainly responsible for filter's selectivity. We previously
described that podocytes express Rab3A, a GTPase restricted to cell
types that are capable of highly regulated exocytosis, such as neuronal
cells. Here, we first demonstrate by a proteomic study that Rab3A
in podocytes coimmmunoprecipitates with molecules once thought to
be synapse specific. We then show that podocytes possess structures
resembling synaptic vesicles, which contain glutamate, coexpress
Rab3A and synaptotagmin 1, and undergo spontaneous and stimulated
exocytosis and recycling, with glutamate release. Finally, from the
results of a cDNA microarray study, we describe the presence of a
series of neuron- and synapse-specific molecules in normal human
glomeruli and confirm the glomerular protein expression of both metabotropic
and ionotropic glutamate receptors. These data point toward a synaptic-like
mechanism of communication among glomerular cells, which perfectly
fits with the molecular composition of the glomerular filter and
puts in perspective several previous observations, proposing a different
working hypothesis for understanding glomerular signaling dynamics.--
Rastaldi, M. P., Armelloni, S., Berra, S., Calvaresi, N., Corbelli,
A., Giardino, L. A., Li, M., Wang, G. Q., Fornasieri, A., Villa,
A., Heikkila, E., Soliymani, R., Boucherot, A., Cohen, C. D., Kretzler,
M., Nitsche, A., Ripamonti, M., Malgaroli, A., Pesaresi, M., Forloni,
G. L., Schlondorff, D., Holthofer, H., D'Amico, G. Glomerular podocytes
contain neuron-like functional synaptic vesicles.},
url = {http://www.fasebj.org/cgi/content/abstract/20/7/976}
}
@ARTICLE{Rastaldi2003,
author = {Rastaldi, Maria Pia and Armelloni, Silvia and Berra, Silvia and Li,
Min and Pesaresi, Marzia and Poczewski, Helga and Langer, Brigitte
and Kerjaschki, Dontscho and Henger, Anna and Blattner, Simone Monika
and Kretzler, Matthias and Wanke, Rudiger and D'Amico, Giuseppe},
title = {Glomerular Podocytes Possess the Synaptic Vesicle Molecule Rab3A
and Its Specific Effector Rabphilin-3a},
journal = {Am. J. Pathol.},
year = {2003},
volume = {163},
pages = {889--899},
number = {3},
month = sep,
abstract = {Several recent studies have focused on similarities between glomerular
podocytes and neurons because the two cells share a specialized cytoskeletal
organization and several expression-restricted proteins, such as
nephrin and synaptopodin. In neurons, the small guanosine triphosphatase
Rab3A and its effector rabphilin-3A form a complex required for the
correct docking of synaptic vesicles to their target membrane. Because
rabphilin-3A binds in neurons to cytoskeletal proteins also important
for podocyte homeostasis, and the complex rabphilin-3A-Rab3A has
been demonstrated in neurons and neuroendocrine cells, the aim of
our work was to investigate their possible expression and regulation
in podocytes. Normal kidneys from mouse, rat, and human were studied
by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase
chain reaction to evaluate the expression of Rab3A and rabphilin-3A.
Double-staining immunohistochemistry and immunogold electron microscopy
were then used to precisely localize the two proteins at the cellular
and subcellular levels. Rab-3A and rabphilin-3A regulations in disease
were then analyzed in growth hormone-transgenic mice, a well established
model of focal and segmental glomerulosclerosis, and in human biopsies
from proteinuric patients. Our results demonstrated that rabphilin-3A
and Rab3A are present in normal mouse, rat, and human kidneys, with
an exclusively glomerular expression and a comma-like pattern of
positivity along the glomerular capillary wall, suggestive for podocyte
staining. Co-localization of both molecules with synaptopodin confirmed
their presence in podocytes. By immunogold electron microscopy both
proteins were found around vesicles contained in podocyte foot processes.
Their expression was increased in growth hormone-transgenic mice
compared to their wild-type counterpart, and in a subset of biopsies
from proteinuric patients. Our data, demonstrating the presence of
two synaptic proteins in podocytes, further supports similarities
between cytoskeletal and vesicular organization of podocytes and
neurons. The altered expression observed in mouse and human proteinuric
diseases suggests a possible role for these molecules in glomerulopathies.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/163/3/889}
}
@ARTICLE{Rate2009,
author = {Rate, Angela and Upham, John W. and Bosco, Anthony and McKenna, Kathy
L. and Holt, Patrick G.},
title = {Airway Epithelial Cells Regulate the Functional Phenotype of Locally
Differentiating Dendritic Cells: Implications for the Pathogenesis
of Infectious and Allergic Airway Disease},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {72--83},
number = {1},
month = jan,
abstract = {Atopic asthma pathogenesis is driven by the combined effects of airway
inflammation generated during responses to viral infections and aeroallergens,
and both these pathways are regulated by dendritic cells (DC) that
differentiate locally from monocytic precursors. These DCs normally
exhibit a sentinel phenotype characterized by active Ag sampling
but attenuated presentation capability, which limits the intensity
of local expression of adaptive immunity. How this tight control
of airway DC functions is normally maintained, and why it breaks
down in some atopics leading to immunopathological changes in airway
tissues, is unknown. We postulated that signals from adjacent airway
epithelial cells (AEC) contribute to regulation of local differentiation
of DC. We tested this in a coculture model containing both cell types
in a GM-CSF-IL-4-enriched cytokine milieu characteristic of the atopic
asthmatic airway mucosa. We demonstrate that contact with AEC during
DC differentiation up-regulates expression of the function-associated
markers MHC class II, CD40, CD80, TLR3, and TLR4 on DCs with concomitant
up-regulation of Ag uptake/processing. Moreover, the AEC-conditioned
DCs displayed increased LPS responsiveness evidenced by higher production
of IL-12, IL-6, IL-10, and TNF-{alpha}. The Th2 memory-activating
properties of AEC-conditioned DCs were also selectively attenuated.
Data from microarray and blocking experiments implicate AEC-derived
type 1 IFNs and IL-6 in modulation of DC differentiation. Collectively,
these findings suggest that resting AECs modulate local DC differentiation
to optimize antimicrobial defenses in the airways and in the process
down-modulate capacity for expression of potentially damaging Th2
immunity.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/1/72}
}
@ARTICLE{Rathinam2010,
author = {Rathinam, Chozhavendan and Thien, Christine B.F. and Flavell, Richard
A. and Langdon, Wallace Y.},
title = {Myeloid Leukemia Development in c-Cbl RING Finger Mutant Mice Is
Dependent on FLT3 Signaling},
journal = {Cancer Cell},
year = {2010},
volume = {18},
pages = {341--352},
number = {4},
month = oct,
abstract = {Summary Although myeloid leukemias are primarily caused by leukemic
stem cells, the molecular basis of their transformation remains largely
unknown. Here, by analyzing mice with a mutation in the RING finger
domain of c-Cbl, we show that the E3 ubiquitin ligase activity of
c-Cbl is required to restrict myeloid leukemia development. These
mice develop a myeloproliferative disease which progresses to leukemia
and involves hematopoietic progenitors that exhibit augmented FLT3
signaling. Suppressing this signaling through matings with FLT3 ligand
knockout mice prevents leukemia development. We also observe enhanced
c-Kit, Akt and Erk activity, and deregulated expression of leukemia-associated
transcription factors in hematopoietic progenitors. The characterization
of these perturbations provides direction for therapeutics that may
aid the treatment of patients with c-Cbl mutations.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-518C1DR-8/2/5b6b12d7f2e451086ee5758d1fb919d9}
}
@ARTICLE{Ratkai2010,
author = {Ratkai, Csilla and Peixe, LuÃsa V. and Grosso, Filipa and Freitas,
Ana R. and Antunes, Patricia and Fodor, Eleonora and Hajdú, Edit
and Nagy, Elisabeth},
title = {Successful application of the DiversiLab repetitive-sequence-based
PCR typing system for confirmation of the circulation of a multiresistant
Pseudomonas aeruginosa clone in different hospital wards},
journal = {Diagn Microbiol Infect Dis},
year = {2010},
volume = {67},
pages = {202--206},
number = {2},
month = jun,
abstract = {The applicability of the repetitive-sequence-based PCR (rep-PCR)–based
DiversiLab system was tested compared with the pulsed field gel electrophoresis
(PFGE) to type a phenotypically similar subset of a large collection
of multiresistant Pseudomonas aeruginosa strains isolated during
a 17-month period from patients treated in different wards including
4 intensive care units (ICUs). Five environmental P. aeruginosa isolates
obtained from one of the ICUs were also included. The DiversiLab
system and the PFGE demonstrated the genetic relationship among the
isolates with the same efficacy. One of the environmental isolates
had the same rep-PCR type as the circulating clone. Multilocus sequence
typing of one of the clinical isolates of the circulating clone proved
that it is a member of a clonal complex of P. aeruginosa that has
not been previously described in clinical samples.},
issn = {0732-8893},
keywords = {Molecular typing methods, Epidemiologic analysis, Multiresistant P.
aeruginosa},
publisher = {Elsevier Biomedical,},
refid = {S0732-8893(10)00014-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0732889310000143?showall=true}
}
@ARTICLE{Rau2010,
author = {Rau, Cheng-Shyuan and Jeng, Jonathan and Jeng, Seng-Feng and Lu,
Tsu-Hsiang and Chen, Yi-Chun and Liliang, Po-Chou and Wu, Chia-Jung
and Lin, Chia-Jung and Hsieh, Ching-Hua},
title = {Entrapment neuropathy results in different microRNA expression patterns
from denervation injury in rats},
journal = {BMC Musculoskeletal Disorders},
year = {2010},
volume = {11},
pages = {181},
number = {1},
abstract = {BACKGROUND:To compare the microRNA (miRNA) expression profiles in
neurons and innervated muscles after sciatic nerve entrapment using
a non-constrictive silastic tube, subsequent surgical decompression,
and denervation injury.METHODS:The experimental L4-L6 spinal segments,
dorsal root ganglia (DRGs), and soleus muscles from each experimental
group (sham control, denervation, entrapment, and decompression)
were analyzed using an Agilent rat miRNA array to detect dysregulated
miRNAs. In addition, muscle-specific miRNAs (miR-1, -133a, and -206)
and selectively upregulated miRNAs were subsequently quantified using
real-time reverse transcription-polymerase chain reaction (real-time
RT-PCR).RESULTS:In the soleus muscles, 37 of the 47 miRNAs (13.4%
of the 350 unique miRNAs tested) that were significantly downregulated
after 6 months of entrapment neuropathy were also among the 40 miRNAs
(11.4% of the 350 unique miRNAs tested) that were downregulated after
3 months of decompression. No miRNA was upregulated in both groups.
In contrast, only 3 miRNAs were upregulated and 3 miRNAs were downregulated
in the denervated muscle after 6 months. In the DRGs, 6 miRNAs in
the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b,
and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320,
and miR-324-3p) were significantly downregulated. No miRNA was upregulated
in both groups. We detected 1 downregulated miRNA (miR-144) and 1
upregulated miRNA (miR-21) after sciatic nerve denervation. We were
able to separate the muscle or DRG samples into denervation or entrapment
neuropathy by performing unsupervised hierarchal clustering analysis.
Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed
an ~50% decrease in miR-1 and miR-133a expression levels at 3 and
6 months after entrapment, whereas miR-1 and miR-133a levels were
unchanged and were decreased after decompression at 1 and 3 months.
In contrast, there were no statistical differences in the expression
of miR-206 during nerve entrapment and after decompression. The expression
of muscle-specific miRNAs in entrapment neuropathy is different from
our previous observations in sciatic nerve denervation injury.CONCLUSIONS:This
study revealed the different involvement of miRNAs in neurons and
innervated muscles after entrapment neuropathy and denervation injury,
and implied that epigenetic regulation is different in these two
conditions.},
doi = {10.1186/1471-2474-11-181},
issn = {1471-2474},
pubmedid = {20704709},
url = {http://www.biomedcentral.com/1471-2474/11/181}
}
@ARTICLE{Raue2007,
author = {Raue, Ulrika and Slivka, Dustin and Jemiolo, Bozena and Hollon, Chris
and Trappe, Scott},
title = {Proteolytic Gene Expression Differs At Rest and After Resistance
Exercise Between Young and Old Women},
journal = {J Gerontol A Biol Sci Med Sci},
year = {2007},
volume = {62},
pages = {1407--1412},
number = {12},
month = dec,
abstract = {Background. Skeletal muscle atrophy in rodents is associated with
increased gene expression of proteolytic markers muscle-RING-finger
protein 1 (MuRF-1) and atrogin-1. In humans with age-related muscle
atrophy, known as sarcopenia, little is known about these key proteolytic
biomarkers. Therefore, the purpose of this investigation was 2-fold:
(i) measure messenger RNA (mRNA) expression of proteolytic genes
MuRF-1, atrogin-1, forkhead box (FOXO)3A, and tumor necrosis factor-{alpha}
(TNF-{alpha}) in young and old women at rest, and (ii) measure these
proteolytic genes in response to an acute resistance exercise (RE)
bout, a known hypertrophic stimulus. Methods. A group of old women
(OW: n = 6, 85 {+/-} 1 years, thigh muscle = 89 {+/-} 4 cm2) and
young women (YW: n = 8, 23 {+/-} 2 years, thigh muscle = 122 {+/-}
6 cm2) performed three sets of 10 knee extensions at 70% of one-repetition
maximum. Muscle biopsies were taken from the vastus lateralis before
and 4 hours after RE. Using real-time reverse transcription-polymerase
chain reaction (RT-PCR), mRNA was amplified and normalized to GAPDH.
Results. At rest, OW expressed higher mRNA levels of MuRF-1 (p =.04)
and FOXO3A (p =.001) compared to YW. In response to RE, there was
an age effect (p =.01) in the induction of atrogin-1 (OW: 2.5-fold).
Both YW and OW had an induction (p =.001) in MuRF-1 (YW: 3.6-fold;
OW: 2.6-fold) with RE. Conclusions. These data show that the regulation
of ubiquitin proteasome-related genes involved with muscle atrophy
are altered in very old women (> 80 years). This finding is manifested
both at rest and in response to RE, which may contribute to the large
degree of muscle loss with age.},
url = {http://biomedgerontology.oxfordjournals.org/cgi/content/abstract/62/12/1407}
}
@ARTICLE{Rauly-Lestienne2011,
author = {Rauly-Lestienne, Isabelle and Lestienne, Fabrice and Ailhaud, Marie-Christine
and Binesse, Johan and Newman-Tancredi, Adrian and Cussac, Didier},
title = {Competitive interaction of 5-HT1A receptors with G-protein subtypes
in CHO cells demonstrated by RNA interference},
journal = {Cellular Signalling},
year = {2011},
volume = {23},
pages = {58--64},
number = {1},
month = jan,
abstract = {Following agonist action, G-protein-coupled receptors may exhibit
differential coupling to G-proteins or second messenger pathways,
supporting the notion of agonist-directed trafficking. To explore
these mechanisms, we have designed and transfected synthetic siRNA
duplexes to knockdown different G[alpha] subunits in Chinese hamster
ovary (CHO) cells expressing human (h)5-hydroxytryptamine 1A receptors
(CHO-h5-HT1A). siRNAs against G[alpha]i2 and G[alpha]i3 transfected
alone or in combination caused a large decrease in the corresponding
mRNA level (64-80%) and also at the protein level for G[alpha]i3
(60-70%), whereas a non-specific siRNA showed no effect. In membranes
of CHO-h5-HT1A, 5-HT stimulated guanosine-5'-O-(3-[35S]thio)-triphosphate
([35S]GTP[gamma]S) binding was differentially affected by transfection
of siRNAs against G[alpha]i protein, siRNAs against G[alpha]i2 inducing
a more important decrease in the efficacy of 5-HT than transfection
of siRNAs against G[alpha]i3. The high potency component was abolished
after transfection of siRNAs against G[alpha]i3 and the lower potency
component was suppressed after transfection of siRNAs against G[alpha]i2.
To directly investigate G[alpha]i3 activation we used an antibody-capture/scintillation
proximity assay. (+)8-OH-DPAT yielded bell-shaped curves for G[alpha]i3
activation, a response that was abolished after transfection of siRNAs
against G[alpha]i3 protein. Interestingly, (+)8-OH-DPAT yielded a
sigmoidal response when only G[alpha]i3 protein was expressed. These
data suggest that when efficacious agonists attain a high level of
occupation of h5-HT1A receptors, a change occurs that induces coupling
to G[alpha]i2 protein and suppresses signalling through G[alpha]i3
subunits.},
issn = {0898-6568},
keywords = {siRNA, 5-HT1A receptor, G proteins, Agonist trafficking},
url = {http://www.sciencedirect.com/science/article/B6T2M-50T41KH-1/2/373078b5f8a9eec1067456f6a367add8}
}
@ARTICLE{Rausch2011,
author = {Rausch, Philipp and Rehman, Ateequr and Kunzel, Sven and Hasler,
Robert and Ott, Stephan J. and Schreiber, Stefan and Rosenstiel,
Philip and Franke, Andre and Baines, John F.},
title = {Colonic mucosa-associated microbiota is influenced by an interaction
of Crohn disease and FUT2 (Secretor) genotype},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {19030-19035},
number = {47},
abstract = {The FUT2 (Secretor) gene is responsible for the presence of ABO histo-blood
group antigens on the gastrointestinal mucosa and in bodily secretions.
Individuals lacking a functional copy of FUT2 are known as "nonsecretors"
and display an array of differences in susceptibility to infection
and disease, including Crohn disease. To determine whether variation
in resident microbial communities with respect to FUT2 genotype is
a potential factor contributing to susceptibility, we performed 454-based
community profiling of the intestinal microbiota in a panel of healthy
subjects and Crohn disease patients and determined their genotype
for the primary nonsecretor allele in Caucasian populations, W143X
(G428A). Consistent with previous studies, we observe significant
deviations in the microbial communities of individuals with Crohn
disease. Furthermore, the FUT2 genotype explains substantial differences
in community composition, diversity, and structure, and we identified
several bacterial species displaying disease-by-genotype associations.
These findings indicate that alterations in resident microbial communities
may in part explain the variety of host susceptibilities surrounding
nonsecretor status and that FUT2 is an important genetic factor influencing
host-microbial diversity.},
doi = {10.1073/pnas.1106408108},
eprint = {http://www.pnas.org/cgi/reprint/108/47/19030.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/47/19030}
}
@ARTICLE{Rautio2007,
author = {Rautio, Jari J. and Huuskonen, Anne and Vuokko, Heikki and Vidgren,
Virve and Londesborough, John},
title = {Monitoring yeast physiology during very high gravity wort fermentations
by frequent analysis of gene expression},
journal = {Yeast},
year = {2007},
volume = {24},
pages = {741--760},
number = {9},
abstract = {Abstract 10.1002/yea.1510.abs Brewer's yeast experiences constantly
changing environmental conditions during wort fermentation. Cells
can rapidly adapt to changing surroundings by transcriptional regulation.
Changes in genomic expression can indicate the physiological condition
of yeast in the brewing process. We monitored, using the transcript
analysis with aid of affinity capture (TRAC) method, the expression
of some 70 selected genes relevant to wort fermentation at high frequency
through 9–10 day fermentations of very high gravity wort (25°P)
by an industrial lager strain. Rapid changes in expression occurred
during the first hours of fermentations for several genes, e.g. genes
involved in maltose metabolism, glycolysis and ergosterol synthesis
were strongly upregulated 2–6 h after pitching. By the time yeast
growth had stopped (72 h) and total sugars had dropped by about 50%,
most selected genes had passed their highest expression levels and
total mRNA was less than half the levels during growth. There was
an unexpected upregulation of some genes of oxygen-requiring pathways
during the final fermentation stages. For five genes, expression
of both the Saccharomyces cerevisiae and S. bayanus components of
the hybrid lager strain were determined. Expression profiles were
either markedly different (ADH1, ERG3) or very similar (MALx1, ILV5,
ATF1) between these two components. By frequent analysis of a chosen
set of genes, TRAC provided a detailed and dynamic picture of the
physiological state of the fermenting yeast. This approach offers
a possible way to monitor and optimize the performance of yeast in
a complex process environment. Copyright © 2007 John Wiley & Sons,
Ltd.},
issn = {1097-0061},
keywords = {yeast physiology, brewer's yeast, gene expression profiling, RNA,
TRAC, expression regulation, fermentation monitoring},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/yea.1510}
}
@ARTICLE{Rautio2006,
author = {Rautio, Jari J. and Kataja, Kari and Satokari, Reetta and Penttilä,
Merja and Söderlund, Hans and Saloheimo, Markku},
title = {Rapid and multiplexed transcript analysis of microbial cultures using
capillary electophoresis-detectable oligonucleotide probe pools},
journal = {Journal of Microbiological Methods},
year = {2006},
volume = {65},
pages = {404--416},
number = {3},
month = jun,
abstract = {A rapid assay for multiplex transcript analysis based on solution
hybridization with pools of oligonucleotide probes was developed.
In this assay called TRAC (transcript analysis with aid of affinity
capture) the mRNAs to be studied are hybridized with gene-specific
detection probe pools and biotinylated oligo(dT) and captured on
streptavidin-coated magnetic particles. Unbound sample material and
nonspecifically bound detection probes are removed and the target-specific
probes are eluted and detected by capillary electrophoresis. Simultaneous
treatment of 96 samples was automated using a magnetic bead particle
processor. The assay enabled detection of in vitro transcribed RNA
at the level of 30 amol (20 pg) and over a 300-fold linear range.
Besides extracted RNA, crude cell lysates were directly used as samples.
The assay was used for transcriptional analysis of selected mRNAs
in the filamentous fungus Trichoderma reesei in two experimental
conditions. TRAC analysis was highly reproducible, providing expression
results that were consistent with conventional Northern blot analysis.
The whole procedure starting from sample collecting can be carried
out in 2 h, making this assay suitable for high-throughput analysis
of a limited set of mRNAs e.g. in gene expression monitoring of production
organism in microbial bioprocesses.},
issn = {0167-7012},
keywords = {Gene expression, Microbial culture monitoring, Oligonucleotide pool
hybridization, Trichoderma reesei},
url = {http://www.sciencedirect.com/science/article/B6T30-4H6XKRN-1/2/b37896d132f2e1787c97b9a521c80fad}
}
@ARTICLE{Raveendran2008,
author = {Raveendran, N. N. and Silver, K. and Freeman, L. C. and Narvaez,
D. and Weng, K. and Ganta, S. and Lillich, J. D.},
title = {Drug-Induced Alterations to Gene and Protein Expression in Intestinal
Epithelial Cell 6 Cells Suggest a Role for Calpains in the Gastrointestinal
Toxicity of Nonsteroidal Anti-Inflammatory Agents},
journal = {J. Pharmacol. Exp. Ther.},
year = {2008},
volume = {325},
pages = {389--399},
number = {2},
month = may,
abstract = {Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively
as therapeutic agents, despite their well documented gastrointestinal
(GI) toxicity. At this time, the mechanisms responsible for NSAID-associated
GI damage are incompletely understood. In this study, we used microarray
analysis to generate a novel hypothesis about cellular mechanisms
that underlie the GI toxicity of NSAIDs. Monolayers of intestinal
epithelial cells (IEC-6) were treated with NSAIDs that either exhibit
(indomethacin, NS-398 [N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide])
or lack (SC-560 [5-(4-chlorphenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole])
inhibitory effects on IEC-6 migration. Bioinformatic analysis of
array data identified the calpain cysteine proteases and their endogenous
inhibitor calpastatin as potential targets of NSAIDs shown previously
to retard IEC-6 migration. Accordingly, quantitative real-time reverse
transcription polymerase chain reaction and immunoblotting were performed
to assess the effects of NSAIDs on the expression of mRNA and protein
for calpain 8, calpain 2, calpain 1, and calpastatin. In treated
IEC-6 monolayers, NS-398 decreased the expression of mRNA for calpain
2 and calpain 8. Both NS-398 and indomethacin decreased the protein
expression of calpains 8, 2, and 1. None of the NSAIDs affected expression
of calpastatin mRNA or protein. The calpain inhibitors, N-acetyl-Leu-Leu-methioninal
and N-acetyl-Leu-Leu-Nle-CHO, retarded IEC-6 cell migration in a
concentration-dependant fashion, and these inhibitory effects were
additive with those of indomethacin and NS-398. Our experimental
results suggest that the altered expression of calpain proteins may
contribute to the adverse effects of NSAIDs on intestinal epithelial
restitution.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/325/2/389}
}
@ARTICLE{Ravenna2009,
author = {Ravenna, Linda and Sale, Patrizio and Di Vito, Maura and Russo, Andrea
and Salvatori, Luisa and Tafani, Marco and Mari, Emanuela and Sentinelli,
Steno and Petrangeli, Elisa and Gallucci, Michele and Di Silverio,
Franco and Russo, Matteo A},
title = {Up-regulation of the inflammatory-reparative phenotype in human prostate
carcinoma},
journal = {Prostate},
year = {2009},
volume = {69},
pages = {1245--1255},
number = {11},
abstract = {Abstract 10.1002/pros.20966.abs BACKGROUND Recent studies have underlined
the role of tumor cells in the endogenous synthesis of pro-inflammatory
molecules. We tested whether malignant progression in prostate cancer
was associated with the activation of a phenotype typical of the
innate immune system. METHODS The expression of a set of molecules
involved in tissue inflammation and repair was measured by real-time
PCR and Western blot analysis in prostate samples in the absence
or slight presence of a detectable leukocyte infiltrate. Whole tumor
and non-tumor samples were analyzed in addition to laser-capture
microdissected tumor and host epithelium. Receptor for advanced glycation
end products, purine receptor, inducible enzymes cyclooxygenase-2
and nitric oxide synthase-2, pentraxin-3 and growth-survival factor
receptors such as epithelial growth factor and estrogen α and β
receptors were all studied. RESULTS A global survey approach showed
an up-regulation in tumor samples of all of the studied genes, with
the exception of ERβ. A laser-capture microdissection approach highlighted
over-expression of pro-inflammatory molecules in each tumor sample
examined. Nuclear translocation of nuclear factor-kB subunit p65
was observed in tumor tissues. CONCLUSIONS These data support the
evidence that molecules typical of the innate immune system, similar
to that of activated leukocytes, are produced by prostate epithelial
cells and that their expression is up-regulated in malignant cells.
We suggest that the observed pro-inflammatory and repair process
activation may represent an important molecular mechanism in the
progression of prostate cancer. Prostate 69:1245–1255, 2009. ©
2009 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {inflammatory and repair process, prostate carcinoma, P2X7R, RAGE,
estrogen receptors},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20966}
}
@ARTICLE{Raverot2010,
author = {Raverot, Gerald and Wierinckx, Anne and Dantony, Emmanuelle and Auger,
Carole and Chapas, Guillaume and Villeneuve, Laurent and Brue, Thierry
and Figarella-Branger, Dominique and Roy, Pascal and Jouanneau, Emmanuel
and Jan, Michel and Lachuer, Joel and Trouillas, Jacqueline and the
members of HYPOPRONOS},
title = {Prognostic Factors in Prolactin Pituitary Tumors: Clinical, Histological,
and Molecular Data from a Series of 94 Patients with a Long Postoperative
Follow-Up},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {1708--1716},
number = {4},
month = apr,
abstract = {Context and Objective: Predicting pituitary tumor behavior remains
a challenge. This multiparameter investigation aimed to identify
markers for recurrence and progression in prolactin tumors. Design:
From a cohort of patients treated for prolactin tumors by surgery,
we retrospectively studied clinical data, tumor characteristics,
clinical outcome, and the expression of nine genes by quantitative
RT-PCR. Results: This study included 94 patients (62 females and
32 men), with long postoperative follow-up periods (mean, 138 {+/-}
46 months); 54.3% of patients had a macro or giant adenoma. Tumors
were classified into three pathological groups based on their radiological
and histological characteristics (noninvasive, 61; invasive, 22;
and aggressive-invasive, 11). Immediately after surgery, 60 patients
(63.8%) went into remission (prolactin level normalization). Persistently
elevated prolactin levels (36.2%) were associated with increasing
age, male sex, high preoperative prolactin levels, large tumor size
on univariate analysis, and invasion and pathological classification
on univariate and multivariate (P = 8 x 10-10 and 3 x 10-8) analysis.
During follow-up, 19 patients (20%) had tumors that recurred or progressed
under dopamine agonist treatment. Invasion and pathological classification
were associated with recurrence or progression on univariate analysis.
Seven genes (ADAMTS6, CRMP1, PTTG, ASK, CCNB1, AURKB, and CENPE)
were associated with tumor recurrence or progression and five of
these (ADAMTS6, CRMP1, ASK, CCNB1, and CENPE) were associated with
the pathological classification. Conclusion: This study identifies
both the clinical and histological factors that relate to prolactin
tumor recurrence or progression. Molecular markers give additional
information for prognosis of such tumors. Altogether, our results
could influence the management of patients with pituitary tumors.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/4/1708}
}
@ARTICLE{Raverot2010a,
author = {Raverot, Gerald and Wierinckx, Anne and Jouanneau, Emmanuel and Auger,
Carole and Borson-Chazot, Francoise and Lachuer, Joel and Pugeat,
Michel and Trouillas, Jacqueline},
title = {Clinical, hormonal and molecular characterization of pituitary ACTH
adenomas without (silent corticotroph adenomas) and with Cushing's
disease},
journal = {Eur. J. Endocrinol.},
year = {2010},
volume = {163},
pages = {35--43},
number = {1},
month = jul,
abstract = {ObjectiveSilent corticotroph adenomas (SCAs) are rare pituitary tumours
immunoreactive for ACTH, but without clinical evidence of Cushing's
disease. We characterized SCAs based on clinical, hormonal and molecular
data, and compared the characteristics of these tumours with those
of macro (MCA)- and micro (mCA)-ACTH adenomas with Cushing's disease.
MethodsFifty ACTH adenomas (14 SCAs, 15 MCAs and 21 mCAs) with complete
corresponding clinical, radiological and biochemical data were selected.
Histological corticotroph differentiation; immunostaining for ACTH,
{beta}-endorphin and {beta}-LPH; and mRNA expression levels of TPIT,
POMC, GR{alpha}, prohormone convertase 1/3 (PC1/3) and galectin-3
were compared in 21 representative tumours. ResultsDespite the absence
of clinical hypercortisolism in patients with SCA, elevated plasma
ACTH levels that were similar to those associated with mCA were observed.
The cortisol/ACTH ratio was similar between SCA and MCA groups and
lower than that found with mCA (P<0.05). This dissociation could
be explained by lower expression of PC1/3 in SCA and MCA than in
mCA (P<0.05). After an i.v. dexamethasone suppression test, ACTH
levels were significantly higher in patients with MCA than in those
with mCA (P<0.05). Cytological and immunocytochemical analyses as
well as mRNA expression levels of TPIT, POMC and GR{alpha} confirmed
corticotroph differentiation in both mCAs and MCAs and in half of
the SCAs, with a strong correlation between TPIT and POMC mRNA expression
levels in SCAs (R2=0.72; P<0.01) and in MCAs (R2=0.65; P<0.05). ConclusionsDespite
the absence of hypercortisolism, SCAs exhibit histological, biochemical
and molecular corticotroph differentiation. SCA and MCA show hormonal
and molecular similarities differentiating them from mCA.},
url = {http://www.eje-online.org/cgi/content/abstract/163/1/35}
}
@ARTICLE{Ravits2005,
author = {Ravits, John and Laurie, Patrick and Stone, Brad},
title = {Amyotrophic Lateral Sclerosis Microgenomics},
journal = {Physical Medicine and Rehabilitation Clinics of North America},
year = {2005},
volume = {16},
pages = {909--924},
number = {4},
month = nov,
booktitle = {Current Trends in Neuromuscular Research: Assessing Function, Enhancing
Performance},
issn = {1047-9651},
url = {http://www.sciencedirect.com/science/article/B75JP-4H8FV9X-8/2/cd5bce8e823bfa566b45924dee902b96}
}
@ARTICLE{Ravoet2009,
author = {Ravoet, Marie and Sibille, Catherine and Gu, Chunyan and Libin, Myriam
and Haibe-Kains, Benjamin and Sotiriou, Christos and Goldman, Michel
and Roufosse, Florence and Willard-Gallo, Karen},
title = {Molecular profiling of CD3-CD4+ T cells from patients with the lymphocytic
variant of hypereosinophilic syndrome reveals targeting of growth
control pathways},
journal = {Blood},
year = {2009},
volume = {114},
pages = {2969--2983},
number = {14},
month = oct,
abstract = {The clonal CD3-CD4+ T-cell population characterizing lymphocytic variant
hypereosinophilic syndrome (L-HES) persists for years, with a subgroup
of patients ultimately progressing to T lymphoma. The molecular changes
associated with the premalignant clone and the emergence of malignant
subclones are unknown, precluding the development of targeted therapy
for this HES variant. In this study, we used whole genome arrays
to examine gene expression in the CD3-CD4+ T cells and found that
850 genes were differentially regulated during chronic disease compared
with CD3+CD4+ T cells from healthy donors. Changes in the expression
of 349 genes were altered in association with the clinical progression
from chronic L-HES to T lymphoma in 1 patient, with 87 of 349 genes
representing further changes in genes whose expression was altered
in all chronic disease patients (87 of 850). Array analysis after
CD2/CD28-mediated activation revealed that the major gene expression
changes observed in the CD3-CD4+ T cells do not reflect activation
induced alterations but rather pathways involved in T-cell homeostasis,
including transforming growth factor-{beta} signaling, apoptosis,
and T-cell maturation, signaling, and migration. Examination of microRNA
expression in the CD3-CD4+ T cells from patients with chronic disease
identified 23 microRNAs that changed significantly, among which miR-125a
further decreased in association with one patient's evolution to
T lymphoma.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/14/2969}
}
@ARTICLE{Rawat2010,
author = {Rawat, Arun and Gust, Kurt A. and Deng, Youping and Garcia-Reyero,
Natalia and Quinn, Michael J., Jr. and Johnson, Mark S. and Indest,
Karl J. and Elasri, Mohamed O. and Perkins, Edward J.},
title = {From raw materials to validated system: the construction of a genomic
library and microarray to interpret systemic perturbations in Northern
bobwhite},
journal = {Physiol Genomics},
year = {2010},
volume = {42},
pages = {219--235},
number = {2},
month = jul,
abstract = {The limited availability of genomic tools and data for nonmodel species
impedes computational and systems biology approaches in nonmodel
organisms. Here we describe the development, functional annotation,
and utilization of genomic tools for the avian wildlife species Northern
bobwhite (Colinus virginianus) to determine the molecular impacts
of exposure to 2,6-dinitrotoluene (2,6-DNT), a field contaminant
of military concern. Massively parallel pyrosequencing of a normalized
multitissue library of Northern bobwhite cDNAs yielded 71,384 unique
transcripts that were annotated with gene ontology (GO), pathway
information, and protein domain analysis. Comparative genome analyses
with model organisms revealed functional homologies in 8,825 unique
Northern bobwhite genes that are orthologous to 48% of Gallus gallus
protein-coding genes. Pathway analysis and GO enrichment of genes
differentially expressed in livers of birds exposed for 60 days (d)
to 10 and 60 mg/kg/d 2,6-DNT revealed several impacts validated by
RT-qPCR including: prostaglandin pathway-mediated inflammation, increased
expression of a heme synthesis pathway in response to anemia, and
a shift in energy metabolism toward protein catabolism via inhibition
of control points for glucose and lipid metabolic pathways, PCK1
and PPARGC1, respectively. This research effort provides the first
comprehensive annotated gene library for Northern bobwhite. Transcript
expression analysis provided insights into the metabolic perturbations
underlying several observed toxicological phenotypes in a 2,6-DNT
exposure case study. Furthermore, the systemic impact of dinitrotoluenes
on liver function appears conserved across species as PPAR signaling
is similarly affected in fathead minnow liver tissue after exposure
to 2,4-DNT.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42/2/219}
}
@ARTICLE{Ray2010,
author = {Ray, Allison E. and Connon, Stephanie A. and Sheridan, Peter P. and
Gilbreath, Jeremy and Shields, Malcolm and Newby, Deborah T. and
Fujita, Yoshiko and Magnuson, Timothy S.},
title = {Intragenomic heterogeneity of the 16S rRNA gene in strain UFO1 caused
by a 100-bp insertion in helix 6},
journal = {FEMS Microbiology Ecology},
year = {2010},
volume = {72},
pages = {343--353},
number = {3},
abstract = {Abstract Two different versions of the 16S rRNA gene, one of which
contained an unusual 100-bp insertion in helix 6, were detected in
isolate UFO1 acquired from the Oak Ridge Integrated Field-Research
Challenge (ORIFRC) site in Tennessee. rRNA was extracted from UFO1
and analyzed by reverse transcriptase-quantitative PCR with insert-
and non-insert-specific primers; only the noninsert 16S rRNA gene
sequence was detected. Similarly, PCR-based screening of a cDNA library
(190 clones) constructed from reverse-transcribed rRNA from UFO1
did not detect any clones containing the 100-bp insert. Examination
of cDNA with primers specific to the insert-bearing 16S rRNA gene,
but downstream of the insert, suggests that the insert was excised
from rRNA. Inspection of other 16S rRNA genes in the GenBank database
revealed that a homologous insert sequence, also found in helix 6,
has been reported in other environmental clones, including those
acquired from ORIFRC enrichments. These findings demonstrate the
existence of widely divergent copies of the 16S rRNA gene within
the same organism, which may confound 16S rRNA gene-based methods
of estimating microbial diversity in environmental samples.},
issn = {1574-6941},
keywords = {16S rRNA genes, gene inserts, intragenomic heterogeneity, intervening
sequence (IVS), helix 6},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6941.2010.00868.x}
}
@ARTICLE{Ray2008,
author = {Ray, Julie Basu and Arab, Sara and Deng, Yupu and Liu, Peter and
Penn, Linda and Courtman, David W. and Ward, Michael E.},
title = {Oxygen regulation of arterial smooth muscle cell proliferation and
survival},
journal = {Am J Physiol Heart Circ Physiol},
year = {2008},
volume = {294},
pages = {H839--852},
number = {2},
month = feb,
abstract = {The purpose of this study was to determine if hypoxia elicits different
proliferative and apoptotic responses in systemic arterial smooth
muscle cells incubated under conditions that do or do not result
in cellular ATP depletion and whether these effects are relevant
to vascular remodeling in vivo. Gene expression profiling was used
to identify potential regulatory pathways. In human aortic smooth
muscle cells (HASMCs) incubated at 3% O2, proliferation and progression
through the G1/S interphase are enhanced. Incubation at 1% O2 reduced
proliferation, delayed G1/S transition, increased apoptotic cell
death, and is associated with mitochondrial membrane depolarization
and reduced cellular ATP levels. In aorta and mesenteric artery from
rats exposed to hypoxia (10% O2, 48 h), both proliferation and apoptosis
are increased, as are medial nuclear density and smooth muscle cell
content. Although nuclear levels of hypoxia-inducible factor 1-{alpha}
(HIF-1{alpha}) are increased to a similar extent in HASMCs incubated
at 1 and 3% O2, expression of tumor protein p53, its transcriptional
target p21, as well as their regulatory factors and downstream effectors,
are differentially affected under these two conditions, suggesting
that the bidirectional effects of hypoxia are mediated by this pathway.
We conclude that hypoxia induces a state of enhanced cell turnover
through increased rates of both smooth muscle cell proliferation
and death. This confers the ability to remodel the vasculature in
response to changing tissue metabolic needs while avoiding the accumulation
of mutations that may lead to malignant transformation or the formation
of abnormal vascular structures.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/294/2/H839}
}
@ARTICLE{Rayalam2008,
author = {Rayalam, Srujana and Yang, Jeong-Yeh and Ambati, Suresh and Della-Fera,
Mary Anne and Baile, Clifton A.},
title = {Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1
adipocytes},
journal = {Phytother. Res.},
year = {2008},
volume = {22},
pages = {1367--1371},
number = {10},
abstract = {Abstract 10.1002/ptr.2503.abs Resveratrol, a phytoallexin, has recently
been reported to slow aging by acting as a sirtuin activator. Resveratrol
also has a wide range of pharmacological effects on adipocytes. In
this study, we investigated the effects of resveratrol on adipogenesis
and apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200
µM resveratrol decreased cell viability dose-dependently by 23 ±
2.7%, and 75.3 ± 2.8% (p < 0.0001), respectively, after 48 h treatment,
and 100 µM resveratrol increased apoptosis by 76 ± 8.7% (p < 0.0001).
Resveratrol at 25 and 50 µM decreased lipid accumulation in maturing
preadipocytes significantly by 43 ± 1.27% and 94.3 ± 0.3% (p <
0.0001) and decreased cell viability by 25 ± 1.3% and 70.4 ± 1.6%
(p < 0.0001), respectively. In order to understand the anti-adipogenic
effects of resveratrol, maturing 3T3-L1 preadipocytes were treated
with 25 µM resveratrol and the change in the expression of several
adipogenic transcription factors and enzymes was investigated using
real-time RT-PCR. Resveratrol down-regulated the expression of PPARγ,
C/EBPα, SREBP-1c, FAS, HSL, LPL and up-regulated the expression
of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2).
These results indicate that resveratrol may alter fat mass by directly
affecting cell viability and adipogenesis in maturing preadipocytes
and inducing apoptosis in adipocytes and thus may have applications
for the treatment of obesity. Copyright © 2008 John Wiley & Sons,
Ltd.},
issn = {1099-1573},
keywords = {resveratrol, 3T3-L1 cells, apoptosis, adipogenesis, adipocyte specific
genes, real-time RT-PCR},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/ptr.2503}
}
@BOOK{Raymond2010,
title = {In Vivo Analysis of Gene Knockdown in Tetracycline-Inducible shRNA
Mice},
publisher = {Academic Press},
year = {2010},
editor = {Wassarman, Paul M. and Soriano, Philippe M.},
author = {Raymond, Christopher S. and Zhu, Lei and Vogt, Thomas F. and Shin,
Myung K.},
volume = {Volume 477},
pages = {415--427},
abstract = {Expression of small hairpin RNA (shRNA) in mammalian cells can trigger
potent RNAi-mediated gene silencing. The dominant-acting RNAi can
often result in phenotypes similar to that of a null allele. Moreover,
the generation of shRNA knockdown mice and subsequent phenotypic
analysis can be achieved in a condensed timeline compared to that
of conventional gene-targeting knockout strategies. Here, we discuss
methods for the in vivo analysis of gene function in adult mouse
tissues following tetracycline-induced RNA knockdown in a single-copy
inducible polymerase III promoter-driven shRNA system.},
booktitle = {Guide to Techniques in Mouse Development, Part B: Mouse Molecular
Genetics, 2nd Edition},
issn = {0076-6879},
keywords = {shRNA, Germ line RNAi, Mice, In vivo analysis, Knockdown, Tet-inducible,
Doxycycline},
url = {http://www.sciencedirect.com/science/article/B7CV2-50R6JF6-X/2/accffc80a9bf87507c6f29033195a4c5}
}
@ARTICLE{Raymond2006,
author = {Raymond, Frédéric and Metairon, Sylviane and Borner, Roland and
Hofmann, Markus and Kussmann, Martin},
title = {Automated Target Preparation for Microarray-Based Gene Expression
Analysis},
journal = {Analytical Chemistry},
year = {2006},
volume = {78},
pages = {6299-6305},
number = {18},
doi = {10.1021/ac060097t},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac060097t},
url = {http://pubs.acs.org/doi/abs/10.1021/ac060097t}
}
@ARTICLE{Raymond2010a,
author = {Raymond, Frederic and Métairon, Sylviane and Kussmann, Martin and
Colomer, Jaume and Nascimento, Andres and Mormeneo, Emma and García-Martínez,
Cèlia and Gómez-Foix, Anna},
title = {Comparative gene expression profiling between human cultured myotubes
and skeletal muscle tissue},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {125},
number = {1},
abstract = {BACKGROUND:A high-sensitivity DNA microarray platform requiring nanograms
of RNA input facilitates the application of transcriptome analysis
to individual skeletal muscle (SM) tissue samples. Culturing myotubes
from SM-biopsies enables investigating transcriptional defects and
assaying therapeutic strategies. This study compares the transcriptome
of aneurally cultured human SM cells versus that of tissue biopsies.RESULTS:We
used the Illumina expression BeadChips to determine the transcriptomic
differences between tissue and cultured SM samples from five individuals.
Changes in the expression of several genes were confirmed by QuantiGene
Plex assay or reverse transcription real-time PCR. In cultured myotubes
compared to the tissue, 1216 genes were regulated: 583 down and 633
up. Gene ontology analysis showed that downregulated genes were mainly
associated with cytoplasm, particularly mitochondria, and involved
in metabolism and the muscle-system/contraction process. Upregulated
genes were predominantly related to cytoplasm, endoplasmic reticulum,
and extracellular matrix. The most significantly regulated pathway
was mitochondrial dysfunction. Apoptosis genes were also modulated.
Among the most downregulated genes detected in this study were genes
encoding metabolic proteins AMPD1, PYGM, CPT1B and UCP3, muscle-system
proteins TMOD4, MYBPC1, MYOZ1 and XIRP2, the proteolytic CAPN3 and
the myogenic regulator MYF6. Coordinated reduced expression of five
members of the GIMAP gene family, which form a cluster on chromosome
7, was shown, and the GIMAP4-reduction was validated. Within the
most upregulated group were genes encoding senescence/apoptosis-related
proteins CDKN1A and KIAA1199 and potential regulatory factors HIF1A,
TOP2A and CCDC80.CONCLUSIONS:Cultured muscle cells display reductive
metabolic and muscle-system transcriptome adaptations as observed
in muscle atrophy and they activate tissue-remodeling and senescence/apoptosis
processes.},
doi = {10.1186/1471-2164-11-125},
issn = {1471-2164},
pubmedid = {20175888},
url = {http://www.biomedcentral.com/1471-2164/11/125}
}
@ARTICLE{Raynaud2005,
author = {Raynaud, Peggy and Gillard, Mélanie and Parr, Tim and Bardsley, Ronald
and Amarger, Valérie and Levéziel, Hubert},
title = {Correlation between bovine calpastatin mRNA transcripts and protein
isoforms},
journal = {Archives of Biochemistry and Biophysics},
year = {2005},
volume = {440},
pages = {46--53},
number = {1},
month = aug,
abstract = {Calpastatin is a specific calpain protease inhibitor: calpains are
a family of calcium-activated neutral proteases, which have been
implicated in various processes. Despite all the available data concerning
calpastatin, little is known about how this gene is regulated, particularly
in bovine. The existence of four types of transcripts differing at
their 5' ends (Type I, II, III, and IV) has been demonstrated. Here,
we show that the Type I, II, and III transcripts are ubiquitous while
Type IV is testis-specific. In addition, a Northern blot analysis
revealed that the Type III transcript may have three different 3'
termini. Using specific anti-peptide anti-sera, a correspondence
between a 145 and a 125 kDa isoforms, and Type I and/or II and III
transcripts, respectively, has been established. Finally, we discuss
the origin of a 70 kDa isoform, recognized by anti-sera directed
against the N-terminal region.},
issn = {0003-9861},
keywords = {Calpastatin, Calpain, Bovine, mRNA expression, Isoforms, Proteolysis,
Western blot, Northern blot},
url = {http://www.sciencedirect.com/science/article/B6WB5-4GFCMTM-1/2/6f49e35e21422d661529af1a8b7fc84b}
}
@ARTICLE{Rayner2004,
author = {Rayner, Jennifer L. and Wood, Carmen and Fenton, Suzanne E.},
title = {Exposure parameters necessary for delayed puberty and mammary gland
development in Long-Evans rats exposed in utero to atrazine},
journal = {Toxicology and Applied Pharmacology},
year = {2004},
volume = {195},
pages = {23--34},
number = {1},
month = feb,
abstract = {Our studies suggested that prenatal exposure to the herbicide atrazine
(ATR) could delay vaginal opening (VO) and mammary development in
the offspring of Long-Evans (LE) rats. To evaluate ATR exposure parameters
required for pubertal delays, including mammary gland development,
we used cross-fostering to determine if effects were strictly dam-mediated
(via milk) or a direct effect (transplacental) on the pups. Timed-pregnant
LE rats (N = 20/treatment group) were gavaged on gestational days
(GD) 15-19 with 100 mg ATR/kg body weight (BW) or vehicle (controls,
C). On PND1, half of all litters were cross-fostered, creating four
treatment groups: C-C, ATR-C, C-ATR, and ATR-ATR (dam-milk source,
respectively). A significant delay in VO and increase in VO BW was
seen only in the litters receiving milk from ATR-exposed dams. However,
mammary glands of female offspring (two per dam) in all groups exposed
to ATR (ATR-C, C-ATR, and ATR-ATR) displayed significant delays in
epithelial development. These changes were detected as early as PND4
and stunted development was evident through PND40. Further, at all
developmental stages examined, offspring in the ATR-ATR group exhibited
the least developed glands. These delays in pubertal endpoints do
not appear to be related to body weight or endocrine hormone concentrations.
Our data suggest that the delay in VO of ATR-exposed offspring (C-ATR
lactationally, ATR-ATR lactationally and in utero) is mediated via
the dam [milk], whereas brief direct exposure to ATR in utero can
cause delays in mammary gland development. Our data suggest that
milk-derived factors (growth factors or hormones), in addition to
transplacental exposure during mammary bud outgrowth, may be involved
in ATR mode of action on delayed mammary gland development.},
issn = {0041-008X},
keywords = {Atrazine, Aromatase, Epidermal growth factor, Mammary development,
Mammary gland, Vaginal opening, Long-Evans, Puberty},
url = {http://www.sciencedirect.com/science/article/B6WXH-4BDY61M-1/2/4ad9c114199c4e61b3fe13fd8520c10c}
}
@ARTICLE{Raza2008,
author = {Raza, Sobia and Robertson, Kevin and Lacaze, Paul and Page, David
and Enright, Anton and Ghazal, Peter and Freeman, Tom},
title = {A logic-based diagram of signalling pathways central to macrophage
activation},
journal = {BMC Systems Biology},
year = {2008},
volume = {2},
pages = {36},
number = {1},
abstract = {BACKGROUND:The complex yet flexible cellular response to pathogens
is orchestrated by the interaction of multiple signalling and metabolic
pathways. The molecular regulation of this response has been studied
in great detail but comprehensive and unambiguous diagrams describing
these events are generally unavailable. Four key signalling cascades
triggered early-on in the innate immune response are the toll-like
receptor, interferon, NF-?B and apoptotic pathways, which co-operate
to defend cells against a given pathogen. However, these pathways
are commonly viewed as separate entities rather than an integrated
network of molecular interactions.RESULTS:Here we describe the construction
of a logically represented pathway diagram which attempts to integrate
these four pathways central to innate immunity using a modified version
of the Edinburgh Pathway Notation. The pathway map is available in
a number of electronic formats and editing is supported by yEd graph
editor software.CONCLUSION:The map presents a powerful visual aid
for interpreting the available pathway interaction knowledge and
underscores the valuable contribution well constructed pathway diagrams
make to communicating large amounts of molecular interaction data.
Furthermore, we discuss issues with the limitations and scalability
of pathways presented in this fashion, explore options for automated
layout of large pathway networks and demonstrate how such maps can
aid the interpretation of functional studies.},
doi = {10.1186/1752-0509-2-36},
issn = {1752-0509},
pubmedid = {18433497},
url = {http://www.biomedcentral.com/1752-0509/2/36}
}
@ARTICLE{Razeghi2006,
author = {Razeghi, Peter and Buksinska-Lisik, Malgorzata and Palanichamy, Nanthini
and Stepkowski, Stanislaw and Frazier, O. Howard and Taegtmeyer,
Heinrich},
title = {Transcriptional regulators of ribosomal biogenesis are increased
in the unloaded heart},
journal = {FASEB J},
year = {2006},
volume = {20},
pages = {1090--1096},
number = {8},
month = jun,
abstract = {Mechanical unloading of the rat heart increases both protein synthesis
and protein degradation. The transcriptional mechanism underlying
increased protein synthesis during atrophic remodeling is not known.
The aim of this study was to identify transcriptional regulators
and the gene expression profile regulating protein synthesis in the
unloaded rat heart and in the unloaded failing human heart. We measured
DNA binding activity, transcript levels, and protein expression of
transcriptional regulators of protein synthesis in a model of atrophic
remodeling induced by heterotopic transplantation of the rat heart
(duration 1 and 7 days). Using microarray analysis and quantitative
RT-polymerase chain reaction, we found an increase in c-myc-regulated
gene expression including an induction of ribosomal subunit messenger
RNA's (RPS 10, RPL 21) and rRNA (18S). Consistent with the gene expression
profile, DNA binding activity of c-myc and the nuclear protein concentration
of its coactivator, upstream binding factor (UBF), increased in the
atrophied heart whereas protein levels of the c-myc inhibitor MAD1
decreased. We found the same increase of ribosomal subunit messenger
RNA and rRNA in 21 paired samples of failing human hearts obtained
before and after left ventricular assist device treatment (mean duration:
157{+/-}31 days). In summary, mechanical unloading increases c-myc
activity and c-myc-regulated gene expression in the rat heart. Changes
in transcript levels of genes regulating ribosomal biogenesis in
the unloaded rat heart resemble those found in the unloaded failing
human heart. We concluded c-myc and c-myc-regulated gene expression
are transcriptional regulators of protein synthesis during atrophic
remodeling of the heart.--Razeghi, P., Buksinska-Lisik, M., Palanichamy,
N., Stepkowski, S., Frazier, O. H., Taegtmeyer, H. Transcriptional
regulators of ribosomal biogenesis are increased in the unloaded
heart.},
url = {http://www.fasebj.org/cgi/content/abstract/20/8/1090}
}
@ARTICLE{Razny2011,
author = {Razny, Urszula and Kiec-Wilk, Beata and Wator, Lukasz and Polus,
Anna and Dyduch, Grzegorz and Solnica, Bogdan and Malecki, Maciej
and Tomaszewska, Romana and Cooke, John and Dembinska-Kiec, Aldona},
title = {Increased nitric oxide availability attenuates high fat diet metabolic
alterations and gene expression associated with insulin resistance},
journal = {Cardiovascular Diabetology},
year = {2011},
volume = {10},
pages = {68},
number = {1},
abstract = {BACKGROUND:High fat diet impairs nitric oxide (NO) bioavailability,
and induces insulin resistance. The link between NO availability
and the metabolic adaptation to a high fat diet is not well characterized.
The purpose of this study was to investigate the effect of high fat
diet on metabolism in mice with decreased (eNOS-/-) and increased
(DDAH overexpressed) NO bioavailability.METHODS:eNOS-/- (n = 16),
DDAH (n = 24), and WT (n = 19) mice were fed a high fat diet (HFD)
for 13 weeks. Body weight, biochemical parameters, adipokines and
insulin were monitored. The matrigel in vivo model with CD31 immunostaining
was used to assess angiogenesis.Gene expression in adipose tissues
was analyzed by microarray and Real Time PCR. Comparisons of the
mean values were made using the unpaired Student t test and p < 0.05
were considered statistically significant.RESULTS:eNOS-/- mice gained
less weight than control WT and DDAH mice. In DDAH mice, a greater
increase in serum adiponectin and a lesser increment in glucose level
was observed. Fasting insulin and cholesterol levels remained unchanged.
The angiogenic response was increased in DDAH mice. In adipose tissue
of DDAH mice, genes characteristic of differentiated adipocytes were
down-regulated, whereas in eNOS-/- mice, genes associated with adipogenesis,
fatty acid and triglyceride synthesis were upregulated.CONCLUSIONS:Our
results indicate that increased NO availability attenuates some HFD
induced alterations in metabolism and gene expression associated
with insulin resistance.},
doi = {10.1186/1475-2840-10-68},
issn = {1475-2840},
pubmedid = {21781316},
url = {http://www.cardiab.com/content/10/1/68}
}
@ARTICLE{Rebelo2009,
author = {Rebelo, Susana L. and Amel-Kashipaz, Mohammad R. and Radford, Paul
M. and Bainbridge, Susan E. and Fiets, Roel and Fang, Johnny and
McDermott, Elizabeth M. and Powell, Richard J. and Todd, Ian and
Tighe, Patrick J.},
title = {Novel markers of inflammation identified in tumor necrosis factor
receptor–associated periodic syndrome (TRAPS) by transcriptomic
analysis of effects of TRAPS-associated tumor necrosis factor receptor
type I mutations in an endothelial cell line},
journal = {Arthritis \& Rheumatism},
year = {2009},
volume = {60},
pages = {269--280},
number = {1},
abstract = {Abstract 10.1002/art.24147.abs Objective To analyze the effects of
tumor necrosis factor receptor–associated periodic syndrome (TRAPS)–associated
mutant tumor necrosis factor receptor type I (TNFRI) expression in
a cell type directly relevant to the inflammation in TRAPS, and to
identify novel markers associated with mutant TNFRI expression. Methods
Transcriptome analysis on 30,000 human genes was performed on SK-Hep-1
human endothelial cells transfected with either wild-type (WT) or
TRAPS-associated mutant TNFRI. Quantitative reverse transcriptase–polymerase
chain reaction and protein expression levels measured by enzyme-linked
immunosorbent assay verified transcriptional changes for selected
genes both in supernatants from cells expressing mutant TNFRI and
in patient plasma. Results Cells expressing mutant TNFRI showed up-regulation
of multiple proinflammatory genes relative to WT transfectants, including
genes for pentraxin 3, granulocyte–macrophage colony-stimulating
factor, granulocyte colony-stimulating factor, CCL2, and CCL5, which
were also expressed as proteins. In addition, the expression of most
of these markers was increased in the plasma and peripheral blood
mononuclear cells from TRAPS patients relative to those from healthy
controls. The cysteine mutations (C33Y and C52F), which are associated
with a more severe clinical phenotype, induced more genes than the
low-penetrance mutation R92Q, which is associated with a milder phenotype.
The expression of most genes was induced by a death domain (DD)–dependent
mechanism, since they were not induced by expression of TNFRI mutants
with an inactivated DD. Conclusion TRAPS-associated TNFRI mutants
induce the expression of multiple genes encoding inflammatory molecules,
cellular receptors, transcription factors, and regulators of apoptosis
in endothelial cells that require the cytoplasmic signaling properties
of the receptor. Different mutants have specific expression profiles,
indicating mutation-specific effects. The expression of some of these
markers was also elevated in samples from TRAPS patients.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.24147}
}
@ARTICLE{Rebouissou2008,
author = {Rebouissou, Sandra and Couchy, Gabrielle and Libbrecht, Louis and
Balabaud, Charles and Imbeaud, Sandrine and Auffray, Charles and
Roskams, Tania and Bioulac-Sage, Paulette and Zucman-Rossi, Jessica},
title = {The [beta]-catenin pathway is activated in focal nodular hyperplasia
but not in cirrhotic FNH-like nodules},
journal = {Journal of Hepatology},
year = {2008},
volume = {49},
pages = {61--71},
number = {1},
month = jul,
abstract = {Background/Aims Focal nodular hyperplasias (FNHs) are benign liver
lesions considered to be a hyperplastic response to increased blood
flow in normal liver. In contrast, FNH-like lesions/nodules occur
in cirrhotic liver but share similar histopathological features.
We conducted a transcriptome analysis to identify biological pathways
deregulated in FNH.Methods Gene expression profiles obtained in FNH
and normal livers were compared. Differentially-expressed genes were
validated using quantitative-RT-PCR in 70 benign liver tumors including
FNH-like lesions.Results Among the deregulated genes in FNHs, 19
displayed physiological restricted distribution in the normal liver.
All six perivenous genes were up-regulated in FNH, whereas 13 periportal
genes were down-regulated. Almost all these genes are known to be
regulated by [beta]-catenin. Glutamine synthetase was markedly overexpressed
in anastomosed areas usually centered on visible veins. Moreover,
activated hypophosphorylated [beta]-catenin protein accumulated in
FNH in the absence of activating mutations. These results suggest
the zonated activation of the [beta]-catenin pathway in FNH, whereas
the other benign hepatocellular tumors, including FNH-like lesions,
demonstrated an entirely different pattern of [beta]-catenin expression.Conclusions
In FNH, increased activation of the [beta]-catenin pathway was found
restricted to enlarged perivenous areas. FNH-like nodules may have
a different pathogenetic origin.},
issn = {0168-8278},
keywords = {Focal nodular hyperplasia, Zonation, [beta]-Catenin, Glutamine synthetase,
Benign tumor, Diagnostic markers, Transcriptome, Microarray},
url = {http://www.sciencedirect.com/science/article/B6W7C-4S9NDSK-1/2/14fb15691709d48afcc735a886e410a1}
}
@ARTICLE{Rebouissou2007,
author = {Rebouissou, Sandra and Imbeaud, Sandrine and Balabaud, Charles and
Boulanger, Virginie and Bertrand-Michel, Justine and Terce, Francois
and Auffray, Charles and Bioulac-Sage, Paulette and Zucman-Rossi,
Jessica},
title = {HNF1{alpha} Inactivation Promotes Lipogenesis in Human Hepatocellular
Adenoma Independently of SREBP-1 and Carbohydrate-response Element-binding
Protein (ChREBP) Activation},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {14437--14446},
number = {19},
month = may,
abstract = {Biallelic inactivating mutations of the transcription factor 1 gene
(TCF1), encoding hepatocyte nuclear factor 1{alpha} (HNF1{alpha})
were identified in 50% of hepatocellular adenomas (HCA) phenotypically
characterized by a striking steatosis. To understand the molecular
basis of this aberrant lipid storage, we performed a microarray transcriptome
analysis validated by quantitative reverse transcription-PCR, Western
blotting, and lipid profiling. In mutated HCA, we showed a repression
of gluconeogenesis coordinated with an activation of glycolysis,
citrate shuttle, and fatty acid synthesis predicting elevated rates
of lipogenesis. Moreover, the strong down-regulation of liver fatty
acid-binding protein suggests that impaired fatty acid trafficking
may also contribute to the fatty phenotype. In addition, transcriptional
profile analysis of the observed deregulated genes in non-HNF1{alpha}-mutated
HCA as well as in non-tumor livers allowed us to define a specific
signature of the HNF1{alpha}-mutated HCA. In these tumors, lipid
composition was dramatically modified according to the transcriptional
deregulations identified in the fatty acid synthetic pathway. Surprisingly,
lipogenesis activation did not operate through sterol regulatory
element-binding protein-1 (SREBP-1) and carbohydrate-response element-binding
protein (ChREBP) that were repressed. We conclude that steatosis
in HNF1{alpha}-mutated HCA results mainly from an aberrant promotion
of lipogenesis that is linked to HNF1{alpha} inactivation and that
is independent of both SREBP-1 and ChREBP activation. Finally, our
findings have potential clinical implications since lipogenesis can
be efficiently inhibited by targeted therapies.},
url = {http://www.jbc.org/cgi/content/abstract/282/19/14437}
}
@ARTICLE{Rebourcet2010,
author = {Rebourcet, D. and Odet, F. and Vérot, A. and Combe, E. and Meugnier,
E. and Pesenti, S. and Leduque, P. and Déchaud, H. and Magre, S.
and Le Magueresse-Battistoni, B.},
title = {The effects of an in utero exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin
on male reproductive function: identification of Ccl5 as a potential
marker},
journal = {International Journal of Andrology},
year = {2010},
volume = {33},
pages = {413--424},
number = {2},
abstract = {Summary 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like
compounds are widely encountered toxic substances suspected of interfering
with the endocrine systems of humans and wildlife, and of contributing
to the loss of fertility. In this study, we determined the changes
in testicular gene expression caused by in utero exposure to TCDD
along with the intra-testicular testosterone levels, epididymal sperm
reserves, daily sperm production (DSP) and testis histology. To this
purpose, female pregnant Sprague–Dawley rats orally received TCDD
(10, 100 or 200Â ng/kg body weight) or vehicle at embryonic day 15,
and the offspring was killed throughout development. Hepatic Cyp1a1
gene expression was measured in the offspring to confirm the exposure
to TCDD. The gross histology of the testes and intra-testicular testosterone
levels were normal among the studied groups. Sperm reserves were
altered in 67-day-old rats of the TCDD-200 group, but not in 145-day-old
animals or in the other TCDD-exposed groups. Nonetheless, fertility
was not altered in males of the TCDD-200 group, and the F2 males
generated had normal sperm reserves and DSP. Microarray analysis
permitted the identification of eight differentially expressed genes
in the 4-week-old testes of the TCDD-200 compared with that of the
control group (cut-off value ± 1.40), including the down-regulated
chemokine Ccl5/Rantes. Inhibition of Ccl5/Rantes gene expression
was observed throughout development in the TCDD-200 group, and at
67 and 145Â days in the TCDD-100 group (animals of younger ages were
not examined). Ccl5/Rantes gene expression was mostly confined in
Leydig cells. F2 males generated from males of the TCDD-200 group
had normal levels of Ccl5/Rantes in testis and Cyp1a1 in liver, which
might indicate that Ccl5/Rantes is a marker of TCDD exposure in testis
such as Cyp1a1 in liver. In conclusion, we demonstrated a decrease
in Ccl5/Rantes RNA levels and a transitory decline in sperm reserves
in the testes of rats of TCDD-dosed dams.},
issn = {1365-2605},
keywords = {2,3,7,8-tetrachlorodibenzo-p-dioxin, Ccl5/Rantes, in utero exposure,
sperm count, testis, transcriptomic analysis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2605.2009.01020.x}
}
@ARTICLE{Recchia2010,
author = {Recchia, Franco M. and Xu, Lili and Penn, John S. and Boone, Braden
and Dexheimer, Phillip J.},
title = {Identification of Genes and Pathways Involved in Retinal Neovascularization
by Microarray Analysis of Two Animal Models of Retinal Angiogenesis},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {1098--1105},
number = {2},
month = feb,
abstract = {Purpose.Comparative retinal gene expression analysis in two rodent
models of oxygen-induced retinopathy (OIR) was performed to identify
the genes and pathways involved in retinal neovascularization. Methods.Three
independent experimental runs were conducted for each species, according
to standard protocols for induction of OIR. Total retinal RNA was
isolated at two time points, corresponding to the early response
to relative hypoxia (P13 in mouse, P15 in rat) and to the later phase
of maximum retinal neovascularization (P18 in mouse, P20 in rat)
and was used to prepare labeled probes for hybridization. Gene expression
was compared between normal and experimental conditions for each
species at each time point. Probesets with a false-discovery rate
of [≤]0.05 were considered significantly different and were classified
as cellular functions or biological pathways. Changes in expression
of selected genes were confirmed by quantitative rtPCR. Results.At
the early time point, there were changes in 43 genes in each species,
with two in common. Increased expression of members of the VEGF and
ephrin receptor signaling pathways were identified in both models.
At the later time point, there were changes in 26 genes in the rat
and in 1622 in the mouse, with 13 in common. Four pathways were identified
in both models. Conclusions.Genes and pathways known to be involved
in angiogenesis, as well as other biologically plausible genes and
pathways, were identified. This work serves as a comprehensive resource
for the study of retinal neovascularization and identification of
potential rational targets for antiangiogenic therapy.},
url = {http://www.iovs.org/cgi/content/abstract/51/2/1098}
}
@ARTICLE{Recuero2009,
author = {Recuero, MarÃa and Vicente, Ma Carmen and MartÃnez-GarcÃa, Ana
and Ramos, MarÃa C. and Carmona-Saez, Pedro and Sastre, Isabel and
Aldudo, Jesús and Vilella, Elisabet and Frank, Ana and Bullido,
MarÃa J. and Valdivieso, Fernando},
title = {A free radical-generating system induces the cholesterol biosynthesis
pathway: a role in Alzheimer's disease},
journal = {Aging Cell},
year = {2009},
volume = {8},
pages = {128--139},
number = {2},
abstract = {Summary Oxidative stress, which plays a critical role in the pathogenesis
of neurodegenerative diseases such as Alzheimer's disease (AD), is
intimately linked to aging – the best established risk factor for
AD. Studies in neuronal cells subjected to oxidative stress, mimicking
the situation in AD brains, are therefore of great interest. This
paper reports that, in human neuronal cells, oxidative stress induced
by the free radical-generating xanthine/xanthine oxidase (X-XOD)
system leads to apoptotic cell death. Microarray analyses showed
a potent activation of the cholesterol biosynthesis pathway following
reductions in the cell cholesterol synthesis caused by the X-XOD
treatment; furthermore, the apoptosis was reduced by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme
A reductase (HMGCR) expression with an interfering RNA. The potential
importance of this mechanism in AD was investigated by genetic association,
and it was found that HMGCR, a key gene in cholesterol metabolism
and among those most strongly upregulated, was associated with AD
risk. In summary, this work presents a human cell model prepared
to mimic the effect of oxidative stress in neurons that might be
useful in clarifying the mechanism involved in free radical-induced
neurodegeneration. Gene expression analysis followed by genetic association
studies indicates a possible link among oxidative stress, cholesterol
metabolism and AD.},
issn = {1474-9726},
keywords = {oxidative stress, cell injury, neurodegeneration, cholesterol, HMGCR,
genetic association, Alzheimer's disease},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1474-9726.2009.00457.x}
}
@ARTICLE{Reddy2005,
author = {Reddy, AP and Bethea, CL},
title = {Preliminary array analysis reveals novel genes regulated by ovarian
steroids in the monkey raphe region.},
journal = {Psychopharmacology (Berl)},
year = {2005},
volume = {180},
pages = {125-40--},
number = {1},
month = jun,
abstract = {We hypothesize that ovarian hormones may improve serotonin neuron
survival. We sought the effect of estradiol (E) and progesterone
(P) on novel gene expression in the macaque dorsal raphe region with
Affymetrix array analysis. Nine spayed rhesus macaques were treated
with either placebo, E or E+P via Silastic implant for 1 month prior
to euthanasia (n=3 per treatment). RNA was extracted from a small
block of midbrain containing the dorsal raphe and examined on an
Agilent Bioanalyzer. The RNA from each monkey was labeled and hybridized
to an Affymetrix HG_U95AV Human GeneChip Array. After filtering and
sorting, 25 named genes remained that were regulated by E, and 24
named genes remained that were regulated by supplemental P. These
genes further sorted into functional categories that would promote
neuronal plasticity, transmitter synthesis, and trafficking, as well
as reduce apoptosis. The relative abundance of four pivotal genes
was examined in all nine animals with quantitative RT-PCR and normalized
by glyceraldehyde 3-phosphate dehydrogenase (GAPDH). E+/-P caused
a significant threefold reduction in JNK-1 (a pro-apoptosis gene,
p<0.007); and a significant sixfold decrease in kynurenine mono-oxygenase
(produces neurotoxic quinolones, p<0.05). GABA-A receptor (alpha3
subunit; benzodiazepine site) and E2F1 (interferes with cytokine
signaling) were unaffected by E, but increased sevenfold (p<0.02)
and fourfold (p<0.009), respectively, upon treatment with P. In summary,
subsets of genes related to tissue remodeling or apoptosis were up-
or down-regulated by E and P in a tissue block containing the dorsal
raphe. These changes could promote cellular resilience in the region
where serotonin neurons originate.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15731897}
}
@ARTICLE{Reddy2007,
author = {Reddy, Akhilesh B. and Maywood, Elizabeth S. and Karp, Natasha A.
and King, Verdun M. and Inoue, Yusuke and Gonzalez, Frank J. and
Lilley, Kathryn S. and Kyriacou, Charalambos P. and Hastings, Michael
H.},
title = {Glucocorticoid signaling synchronizes the liver circadian transcriptome},
journal = {Hepatology},
year = {2007},
volume = {45},
pages = {1478--1488},
number = {6},
abstract = {Abstract 10.1002/hep.21571.abs Circadian control of physiology is
mediated by local, tissue-based clocks, synchronized to each other
and to solar time by signals from the suprachiasmatic nuclei (SCN),
the master oscillator in the hypothalamus. These local clocks coordinate
the transcription of key pathways to establish tissue-specific daily
metabolic programs. How local transcriptomes are synchronized across
the organism and their relative contribution to circadian output
remain unclear. In the present study we showed that glucocorticoids
alone are able to synchronize expression of about 60% of the circadian
transcriptome. We propose that synchronization occurs directly by
the action of glucocorticoids on a diverse range of downstream targets
and indirectly by regulating the core clock genes mPer1, Bmal1, mCry1,
and Dbp. We have identified the pivotal liver transcription factor,
HNF4α, as a mediator of circadian and glucocorticoid-regulated transcription,
showing that it is a key conduit for downstream targeting. Conclusion:
We have demonstrated that by orchestrating transcriptional cascades,
glucocorticoids are able to direct synchronization of a diverse range
of functionally important circadian genes. (HEPATOLOGY 2007;45:1478–1488.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.21571}
}
@ARTICLE{Reddy2011,
author = {Reddy, E M and Chettiar, S T and Kaur, N and Ganeshkumar, R and Shepal,
V and Shanbhag, N C and Shiras, A},
title = {Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion
and tumorigenicity of glioma stem cells},
journal = {Cancer Gene Ther},
year = {2011},
volume = {18},
pages = {206--218},
number = {3},
month = mar,
issn = {0929-1903},
publisher = {Nature America, Inc.},
url = {http://dx.doi.org/10.1038/cgt.2010.71}
}
@ARTICLE{Reddy2008,
author = {Reddy, Padmalatha and Legault, Holly and Sypek, Joseph and Collins,
Mark and Goad, Elizabeth and Goldman, Samuel and Liu, Wei and Murray,
Stuart and Dorner, Andrew and O'Toole, Margot},
title = {Mapping similarities in mTOR pathway perturbations in mouse lupus
nephritis models and human lupus nephritis},
journal = {Arthritis Research \& Therapy},
year = {2008},
volume = {10},
pages = {R127},
number = {6},
abstract = {INTRODUCTION:Treatment with sirolimus, a mammalian target of rapamycin
(mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr
and NZB × NZW F1 mouse models of lupus nephritis, indicating a critical
role for the mTOR pathway in both models. This type of demonstration
of efficacy in animal models is usually a pre-requisite for advancement
into clinical development. However, efficacy in an animal model often
has not translated to the desired activity in the clinic. Therefore,
a more profound understanding of the mechanistic similarities and
differences between various animal models and human diseases is highly
desirable.METHODS:Transcriptional profiling was performed on kidneys
from mice with lupus nephritis; from mice who had efficacious drug
treatment; and from mice before they developed nephritis. Analysis
of variance with false discovery rate adjusted to p < 0.05 and an
average fold change of two or more was used to identify transcripts
significantly associated with disease and response to therapy. Pathway
analyses (using various bioinformatics tools) were carried out to
understand the basis for drug efficacy in the mouse model. The relevance
in human lupus of the pathways identified in the mouse model was
explored using information from several databases derived from the
published literature.RESULTS:We identified a set of nephritis-associated
genes in mouse kidney. Expression of the majority of these returned
to asymptomatic levels on sirolimus treatment, confirming the correlation
between expression levels and symptoms of nephritis. Network analysis
showed that many of these nephritis genes are known to interact with
the mTOR pathway. This led us to ask what human diseases are linked
to the mTOR pathway. We constructed the mTOR pathway interactome
consisting of proteins that interact with members of the mTOR pathway
and identified a strong association between mTOR pathway genes and
genes reported in the literature as being involved in human lupus.CONCLUSIONS:Our
findings implicate the mTOR pathway as a critical contributor to
human lupus. This broad pathway-based approach to understanding the
similarities in, and differences between, animal models and human
diseases may have broader utility.},
doi = {10.1186/ar2541},
issn = {1478-6354},
pubmedid = {18980674},
url = {http://arthritis-research.com/content/10/6/R127}
}
@ARTICLE{Reddy2010,
author = {Reddy, Pichili Vijaya Bhaskar and Lungu, Gina and Kuang, Xianghong
and Stoica, George and Wong, Paul K.Y.},
title = {Neuroprotective effects of the drug GVT (monosodium luminol) are
mediated by the stabilization of Nrf2 in astrocytes},
journal = {Neurochemistry International},
year = {2010},
volume = {56},
pages = {780--788},
number = {6-7},
month = may,
abstract = {Oxidative stress is implicated in various kinds of neurological disorders,
including human immunodeficiency virus (HIV) associated dementia
(HAD). Our laboratory has been studying the murine retrovirus ts1,
a pathogenic mutant of the Moloney murine leukemia virus (MoMuLV),
as a model for HAD. Like HIV in humans, ts1 induces oxidative stress
and progressive neurodegeneration in mice. We have shown previously
that an antioxidant and anti-inflammatory drug GVT or MSL (monosodium
luminol) suppresses ts1-induced oxidative stress, attenuates the
development of spongiform encephalopathy, and delays hind limb paralysis
in infected mice. It is known that upregulation of the nuclear transcription
factor NF-E2-related factor 2 (Nrf2) is involved in upregulating
cellular antioxidant defenses. Since Nrf2 is associated with elevation
of antioxidant defenses in general, and since GVT suppresses ts1-induced
neurodegeneration, our aim in this study was to determine whether
GVT neuroprotection is linked to Nrf2 upregulation in the brain.
We report here that GVT upregulates the levels of Nrf2, both in primary
astrocyte cultures and in brainstem of ts1-infected mice. Significant
upregulation of Nrf2 expression by GVT occurs in both the cytosolic
and nuclear fractions of cultured astrocytes and brainstem cells.
Notably, although GVT treatment increases Nrf2 protein levels in
cultured astrocytes and brainstem tissues, Nrf2 mRNA levels are not
altered. This suggests that the neuroprotective effects of GVT may
be mediated by the stabilization of the Nrf2 protein, allowing continuous
upregulation of Nrf2 levels in the astrocytes.},
issn = {0197-0186},
keywords = {Oxidative stress, GVT, Nrf2, Moloney murine leukemia virus-ts1, HAD},
url = {http://www.sciencedirect.com/science/article/B6T0B-4YJ6G6W-1/2/cbe8365a8d08edd2c0e287fb0f6d8098}
}
@ARTICLE{Reddy2010a,
author = {Reddy, Venkatapuram Seenu and Prabhu, Sumanth D. and Mummidi, Srinivas
and Valente, Anthony J. and Venkatesan, Balachandar and Shanmugam,
Prakashsrinivasan and Delafontaine, Patrice and Chandrasekar, Bysani},
title = {Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes
via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1
and NF-{kappa}B activation},
journal = {Am J Physiol Heart Circ Physiol},
year = {2010},
volume = {299},
pages = {H1242--1254},
number = {4},
month = oct,
abstract = {IL-18 and the extracellular matrix metalloproteinase (MMP) inducer
(EMMPRIN) stimulate the expression of proinflammatory cytokines and
MMPs and are elevated in myocardial hypertrophy, remodeling, and
failure. Here, we report several novel findings in primary cardiomyocytes
treated with IL-18. First, IL-18 activated multiple transcription
factors, including NF-{kappa}B (p50 and p65), activator protein (AP)-1
(cFos, cJun, and JunD), GATA, CCAAT/enhancer-binding protein, myocyte-specific
enhancer-binding factor, interferon regulatory factor-1, p53, and
specific protein (Sp)-1. Second, IL-18 induced EMMPRIN expression
via myeloid differentiation primary response gene 88/IL-1 receptor-associated
kinase/TNF receptor-associated factor-6/JNK-dependent Sp1 activation.
Third, IL-18 induced a number of MMP genes, particularly MMP-9, at
a rapid rate as well as tissue inhibitor of metalloproteinase (TIMP)-1
and TIMP-3 at a slower rate. Finally, the IL-18 induction of MMP-9
was mediated in part via EMMPRIN and through JNK- and ERK-dependent
AP-1 activation and p38 MAPK-dependent NF-{kappa}B activation. These
results suggest that the elevated expression of IL-18 during myocardial
injury and inflammation may favor EMMPRIN and MMP induction and extracellular
matrix degradation. Therefore, targeting IL-18 or its signaling pathways
may be of potential therapeutic benefit in adverse remodeling.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/299/4/H1242}
}
@ARTICLE{Redell2009,
author = {Redell, John B. and Liu, Yin and Dash, Pramod K.},
title = {Traumatic brain injury alters expression of hippocampal microRNAs:
Potential regulators of multiple pathophysiological processes},
journal = {J. Neurosci. Res.},
year = {2009},
volume = {87},
pages = {1435--1448},
number = {6},
abstract = {Abstract 10.1002/jnr.21945.abs Multiple cellular, molecular, and biochemical
changes contribute to outcome after traumatic brain injury (TBI).
MicroRNAs (miRNAs) are known to influence many important cellular
processes, including proliferation, apoptosis, neurogenesis, angiogenesis,
and morphogenesis, all processes that are involved in TBI pathophysiology.
However, it has not yet been determined whether miRNA expression
is altered after TBI. In the present study, we used a microarray
platform to examine changes in the hippocampal expression levels
of 444 verified rodent miRNAs at 3 and 24 hr after controlled cortical
impact injury. Our analysis found 50 miRNAs exhibited decreased expression
levels and 35 miRNAs exhibited increased expression levels in the
hippocampus after injury. We extended the microarray findings using
quantitative polymerase chain reaction analysis for a subset of the
miRNAs with altered expression levels (miR-107, -130a, -223, -292-5p,
-433-3p, -451, -541, and -711). Bioinformatic analysis of the predicted
targets for this panel of miRNAs revealed an overrepresentation of
proteins involved in several biological processes and functions known
to be initiated after injury, including signal transduction, transcriptional
regulation, proliferation, and differentiation. Our results indicate
that multiple protein targets and biological processes involved in
TBI pathophysiology may be regulated by miRNAs. © 2008 Wiley-Liss,
Inc.},
issn = {1097-4547},
keywords = {miRNA, microarray, hippocampus, TBI},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.21945}
}
@ARTICLE{Reder2008,
author = {Reder, Alexander and Höper, Dirk and Weinberg, Christin and Gerth,
Ulf and Fraunholz, Martin and Hecker, Michael},
title = {The Spx paralogue MgsR (YqgZ) controls a subregulon within the general
stress response of Bacillus subtilis},
journal = {Molecular Microbiology},
year = {2008},
volume = {69},
pages = {1104--1120},
number = {5},
abstract = {Summary The alternative sigma factor σB of Bacillus subtilis is responsible
for the induction of the large general stress regulon comprising
approximately 150–200 genes. YqgZ, a member of the σB regulon,
resembles the global regulator Spx of the diamide stress regulon
in B. subtilis. In this work we conducted a comprehensive transcriptome
and proteome analysis of the B. subtilis wild-type 168 and its isogenic
ΔsigB and ΔyqgZ mutants following exposure to 4% (v/v) ethanol
stress, which led to the characterization of a ‘subregulon’ within
the general stress response that is regulated by YqgZ. Activation
and induction of σB are necessary but not sufficient for a full
expression of all general stress genes. Expression of 53 genes was
found to be positively regulated and the expression of 18 genes was
negatively affected by YqgZ. The identification of the negatively
regulated group represents a so far uncharacterized regulatory phenomenon
observed in the ΔsigB mutant background that can now be attributed
to the function of YqgZ. Due to the strict σB-dependent expression
of YqgZ it was renamed to MgsR (modulator of the general stress response).},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2008.06332.x}
}
@ARTICLE{Rederstorff2011,
author = {Rederstorff, Mathieu and Huttenhofer, Alexander},
title = {cDNA library generation from ribonucleoprotein particles},
journal = {Nat. Protocols},
year = {2011},
volume = {6},
pages = {166--174},
number = {2},
month = jan,
comment = {10.1038/nprot.2010.186},
issn = {1754-2189},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nprot.2010.186}
}
@ARTICLE{Redmer2005,
author = {Redmer, Dale A. and Aitken, Raymond P. and Milne, John S. and Reynolds,
Lawrence P. and Wallace, Jacqueline M.},
title = {Influence of Maternal Nutrition on Messenger RNA Expression of Placental
Angiogenic Factors and Their Receptors at Midgestation in Adolescent
Sheep},
journal = {Biol Reprod},
year = {2005},
volume = {72},
pages = {1004--1009},
number = {4},
month = apr,
abstract = {Previous studies have shown that placental growth and pregnancy outcome
are severely compromised in adolescent ewes overnourished to promote
rapid maternal growth. Using this paradigm, the aim of the present
study was to investigate expression of the major angiogenic factors
and their receptors in the placenta at the onset of the most rapid
phase of fetal growth. Singleton pregnancies to a single sire were
established by embryo transfer, and thereafter, adolescent dams were
offered a high or moderate nutrient intake predicted to induce compromised
or normal fetoplacental size at term, respectively. Ovine-specific
oligonucleotide probe and primer sets for several angiogenic factors
and their receptors were developed for quantitative real-time reverse
transcription-polymerase chain reaction determination of placentome
mRNA expression at Day 81 of gestation. Total placentome weight and
fetal weight were equivalent in high- compared with moderate-intake
groups at this stage of gestation. Placentome expression of the angiogenic
factors, vascular endothelial growth factor, angiopoietins 1 and
2, and nitric oxide synthase 3, were reduced in overfed ewes. Similarly,
level of expression of vascular endothelial growth factor/vascular
permeability factor receptor (FLT1) was less in overfed ewes. Thus,
in the adolescent, maternal overnutrition has a negative impact on
midgestation placental angiogenic factor/ receptor expression. This
may impact placental vascularity and explain why uteroplacental mass,
blood flow, and nutrient uptake are compromised in late pregnancy,
resulting in low-birth-weight offspring.},
url = {http://www.biolreprod.org/cgi/content/abstract/72/4/1004}
}
@ARTICLE{Redmer2012,
author = {D.A. Redmer and J.S. Milne and R.P. Aitken and M.L. Johnson and P.P.
Borowicz and L.P. Reynolds and J.S. Caton and J.M. Wallace},
title = {Decreasing maternal nutrient intake during the final third of pregnancy
in previously overnourished adolescent sheep: Effects on maternal
nutrient partitioning and feto-placental development},
journal = {Placenta},
year = {2012},
volume = {33},
pages = {114 - 121},
number = {2},
abstract = {When pregnant adolescent sheep are overnourished during pregnancy
normal nutrient partitioning priorities to the gravid uterus are
altered, leading to impaired placental development and fetal growth
restriction. We hypothesized that decreasing dietary intake in overnourished
dams during the final third of gestation may reverse this inappropriate
nutrient partitioning in favor of the fetus. Adolescent ewes were
offered control (C; n = 12) or high (H; n = 20) dietary intakes
to induce normal vs. compromised placental development. Ten ewes
receiving the H intake were switched to a low intake at d90 of gestation
(HL). Between d90 to 130, HL dams lost weight and adiposity, and
metabolic hormones and glucose at d130 were less than H and similar
to C. In spite of these maternal changes, at d130 fetal bodyweight
was equivalent in HL and H groups and ∼20% less than in C. A greater
degree of brain sparing was evident in HL fetuses and glucose and
insulin concentrations were more perturbed than in H fetuses. Relative
to C, placentome weight was reduced by 46 and 32% in H and HL and
the fetal:placentome weight ratio was HÂ >Â HLÂ >Â C. Placental
vascular morphology was largely unaffected by maternal diet during
late gestation but mRNA expression of five angiogenic genes was up-regulated
in the fetal cotyledon of HL pregnancies, commensurate with blood
vessel remodeling. Nevertheless, overfeeding to promote maternal
anabolic growth during adolescent pregnancy impairs feto-placental
development that cannot be rescued by reducing maternal intake during
the final third of gestation.},
doi = {10.1016/j.placenta.2011.11.023},
issn = {0143-4004},
keywords = {Adolescent pregnancy},
url = {http://www.sciencedirect.com/science/article/pii/S0143400411005558}
}
@ARTICLE{Redmond2008,
author = {Redmond, Latasha C. and Dumur, Catherine I. and Archer, Kellie J.
and Haar, Jack L. and Lloyd, Joyce A.},
title = {Identification of erythroid-enriched gene expression in the mouse
embryonic yolk sac using microdissected cells},
journal = {Dev. Dyn.},
year = {2008},
volume = {237},
pages = {436--446},
number = {2},
abstract = {Abstract 10.1002/dvdy.21426.abs Little is known about the genes that
control the embryonic erythroid program. Laser capture microdissection
was used to isolate primitive erythroid precursors and epithelial
cells from frozen sections of the embryonic day 9.5 yolk sac. The
RNA samples were amplified and labeled for hybridization to Affymetrix
GeneChip Mouse Genome 430A 2.0 arrays. Ninety-one genes are expressed
significantly higher in erythroid than in epithelial cells. Ingenuity
pathway analysis indicates that many of these erythroid-enriched
genes cluster in highly significant biological networks. One of these
networks contains RBTN2/LMO2, SCL/TAL1, and EKLF/KLF1, three of the
very few genes required for primitive erythropoiesis. Quantitative
real-time polymerase chain reaction was used to verify that platelet
factor 4, reelin, thrombospondin-1, and muscleblind-like 1 mRNA is
erythroid-enriched. These genes have established roles in development
or differentiation in other systems, and are, therefore, good candidates
for regulating primitive erythropoiesis. These results provide a
catalog of genes expressed during primitive erythropoiesis. Developmental
Dynamics 237:436–446, 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-0177},
keywords = {mouse yolk sac, laser capture microdissection, embryonic erythroid
cells, erythroid development, oligonucleotide microarrays, primitive
erythropoiesis},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.21426}
}
@ARTICLE{Redmond2008a,
author = {Redmond, Latasha C. and Haar, Jack L. and Giebel, Mary L. and Dumur,
Catherine I. and Basu, Priyadarshi and Ware, Joy L. and Lloyd, Joyce
A.},
title = {Isolation of erythroid cells from the mouse embryonic yolk sac by
laser capture microdissection and subsequent microarray hybridization},
journal = {Blood Cells, Molecules, and Diseases},
year = {2008},
volume = {37},
pages = {27--32},
number = {1},
month = jul,
abstract = {Erythropoietic tissues are complex, containing both erythroid and
other cells. The embryonic yolk sac in particular contains primitive
erythroid cells in low abundance. Laser capture microdissection (LCM)
was performed to isolate erythroid cells, and epithelial cells, from
mouse embryonic day 10 (E10) yolk sac. Quantitative RT-PCR was performed
to confirm that enriched cell populations were obtained. [epsilon]y-
and [beta]H1-globin mRNAs were enriched in the erythroid compared
to the epithelial fraction, and villin mRNA was enriched in the epithelial
compared to the erythroid fraction. RNA isolated from the microdissected
erythroid cells was of high quality as indicated by capillary electrophoresis.
The RNA from the LCM erythroid fraction was linearly amplified with
T7 RNA polymerase and hybridized to a Mouse 430A 2.0 Affymetrix®
array. Forty-eight percent of genes were present in the microarray
assays, including low abundance transcripts such as erythroid transcription
factors and enzymes involved in heme synthesis. With the LCM/microarray
strategy, it will be possible to identify genes that are differentially
regulated in native primitive and definitive erythroid cells.},
issn = {1079-9796},
keywords = {Laser capture microdissection, Embryonic yolk sac erythroid cells,
Primitive erythroid cells, Oligonucleotide microarrays},
url = {http://www.sciencedirect.com/science/article/B6WBV-4JXY7D7-1/2/03b4929f87beb5780e22e8342730485b}
}
@ARTICLE{Reece2006,
author = {Reece, Joshua J. and Siracusa, Mark C. and Scott, Alan L.},
title = {Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively
Activated Alveolar Macrophages},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {4970--4981},
number = {9},
month = sep,
abstract = {While it is well established that infection with the rodent hookworm
Nippostrongylus brasiliensis induces a strongly polarized Th2 immune
response, little is known about the innate host-parasite interactions
that lead to the development of this robust Th2 immunity. We exploited
the transient pulmonary phase of N. brasiliensis development to study
the innate immune responses induced by this helminth parasite in
wild-type (WT) and severe-combined immune deficient (SCID) BALB/c
mice. Histological analysis demonstrated that the cellular infiltrates
caused by N. brasiliensis transit through the lungs were quickly
resolved in WT mice but not in SCID mice. Microarray-based gene expression
analysis demonstrated that there was a rapid induction of genes encoding
molecules that participate in innate immunity and in repair/remodeling
during days 2 to 4 postinfection in the lungs of WT and SCID mice.
Of particular note was the rapid upregulation in both WT and SCID
mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role
for alternatively activated macrophages (AAMs) in pulmonary innate
immunity. Immunohistochemistry revealed that nearly all alveolar
macrophages became YM1-producing AAMs as early as day 2 postinfection.
While the innate responses induced during the lung phase of N. brasiliensis
infection were similar in complexity and magnitude in WT and SCID
mice, only mice with functional T cells were capable of maintaining
elevated levels of gene expression beyond the innate window of reactivity.
The induction of alternatively activated alveolar macrophages could
be important for dampening the level of inflammation in the lungs
and contribute to the long-term decrease in pulmonary inflammation
that has been associated with helminth infections.},
url = {http://iai.asm.org/cgi/content/abstract/74/9/4970}
}
@ARTICLE{Reece2008,
author = {Reece, Joshua J. and Siracusa, Mark C. and Southard, Teresa L. and
Brayton, Cory F. and Urban, Joseph F., Jr. and Scott, Alan L.},
title = {Hookworm-Induced Persistent Changes to the Immunological Environment
of the Lung},
journal = {Infect. Immun.},
year = {2008},
volume = {76},
pages = {3511--3524},
number = {8},
month = aug,
abstract = {A number of important helminth parasites of humans have incorporated
short-term residence in the lungs as an obligate phase of their life
cycles. The significance of this transient pulmonary exposure to
the infection and immunity is not clear. Employing a rodent model
of infection with hookworm (Nippostrongylus brasiliensis), we characterized
the long-term changes in the immunological status of the lungs induced
by parasite infection. At 36 days after infection, alterations included
a sustained increase in the transcription of both Th2 and Th1 cytokines
as well as a significant increase in the number and frequency of
alveolar macrophages displaying an alternatively activated phenotype.
While N. brasiliensis did not induce alternate activation of lung
macrophages in STAT6-/- animals, the parasite did induce a robust
Th17 response in the pulmonary environment, suggesting that STAT6
signaling plays a role in modulating Th17 immunity and pathology
in the lungs. In the context of the cellular and molecular changes
induced by N. brasiliensis infection, there was a significant reduction
in overall airway responsiveness and lung inflammation in response
to allergen. In addition, the N. brasiliensis-altered pulmonary environment
showed dramatic alterations in the nature and number of genes that
were up- and downregulated in the lung in response to allergen challenge.
The results demonstrate that even a transient exposure to a helminth
parasite can effect significant and protracted changes in the immunological
environment of the lung and that these complex molecular and cellular
changes are likely to play a role in modulating a subsequent allergen-induced
inflammatory response.},
url = {http://iai.asm.org/cgi/content/abstract/76/8/3511}
}
@ARTICLE{Reed2008,
author = {Reed, K. M. and Mendoza, K. M. and Juneja, B. and Fahrenkrug, S.
C. and Velleman, S. and Chiang, W. and Strasburg, G. M.},
title = {Characterization of expressed sequence tags from turkey skeletal
muscle},
journal = {Animal Genetics},
year = {2008},
volume = {39},
pages = {635--644},
number = {6},
abstract = {Summary This study was designed to identify important muscle gene
homologues in the turkey. Three skeletal muscle cDNA libraries representing
distinct muscle developmental stages were constructed. A total of
20Â 042 clones were sequenced resulting in 13Â 023 finished high-quality
sequences (trimmed, quality scored and masked) for analysis. Sequence
clustering produced 1113 contigs and 4144 singletons (5257 putative
transcripts). Sequences were compared by blastn to the chicken whole-genome
sequence and to the Ensembl and NCBI databases to identify homologous
sequences. These surveys indicated that most of the important muscle
genes are included in the sequence collection. Examination of contigs
identified 1288 single nucleotide polymorphisms and in 320 of those
the minor allele was observed to be present in more than one sequence.
This resource provides sequence variants for numerous genes in the
turkey, as demonstrated by the SNP haplotypes that were constructed
for 10 genes. Sequences obtained in this study provide the basis
for constructing a skeletal muscle-focused microarray, a tool that
will facilitate the analysis of genes expressed during turkey muscle
development, as well as the expression of genes underlying the genetic
basis of muscle characteristics associated with meat quality.},
issn = {1365-2052},
keywords = {expressed sequence tag, muscle, single nucleotide polymorphism, turkey},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2008.01787.x}
}
@ARTICLE{Reed-Maldonado2009,
author = {Reed-Maldonado, Amanda B and Parekh, Dipen J and Eid, Assaad and
Gosh-Choudhury, Goutam and Gorin, Yves and Abboud, Hanna E and Block,
Karen},
title = {Nad(p)h oxidase subunit p22phox mediates hypoxia-inducible factor-2-alpha
transcriptional activity and is over-expressed in human renal cell
carcinoma},
journal = {The Journal of Urology},
year = {2009},
volume = {181},
pages = {33--34},
number = {4, Supplement 1},
month = apr,
booktitle = {AUA Annual Meeting Program Abstracts, 2009 AUA Annual Meeting},
issn = {0022-5347},
url = {http://www.sciencedirect.com/science/article/B7XMT-4VTWN64-3D/2/57aeff1e6fe111539a47ca62cb4458a7}
}
@ARTICLE{Reedy2010,
author = {Reedy, Carmen R. and Bienvenue, Joan M. and Coletta, Lisa and Strachan,
Briony C. and Bhatri, Naila and Greenspoon, Susan and Landers, James
P.},
title = {Volume reduction solid phase extraction of DNA from dilute, large-volume
biological samples},
journal = {Forensic Science International: Genetics},
year = {2010},
volume = {4},
pages = {206--212},
number = {3},
month = apr,
abstract = {Microdevices are often designed to process sample volumes on the order
of tens of microliters and cannot typically accommodate larger volume
samples without adversely affecting efficiency and greatly increasing
analysis time. However, dilute, large-volume biological samples are
frequently encountered, especially in forensic or clinical laboratories.
A microdevice, capable of efficiently processing 0.5-1 mL samples
has been developed for solid phase extraction (SPE) of DNA. SPE was
carried out on a microdevice utilizing magnetic silica particles
and an optimized volumetric flow rate and elution buffer, resulting
in a 50-fold decrease in volume and a 15-fold increase in DNA concentration.
Device characterization studies showed DNA extraction efficiencies
comparable with previously reported silica-based purification methods,
with robust performance demonstrated by the successful amplification
of a fragment from the gelsolin gene extracted from dilute whole
blood. In addition, the microchip-based method for SPE of large volume,
dilute samples was also used to demonstrate the first successful
on-chip purification of mitochondrial DNA (mtDNA) from both dilute
whole blood and a degraded blood stain.},
issn = {1872-4973},
keywords = {Microfluidics, DNA, Extraction, Mitochondrial DNA, Blood stain},
url = {http://www.sciencedirect.com/science/article/B8CX7-4XF8MRF-1/2/66d56deb21bca1f13126e3b9638b5476}
}
@ARTICLE{Reekmans2005,
author = {Reekmans, Rieka and Smet, Kris De and Chen, Cuiying and Hummelen,
Paul Van and Contreras, Roland},
title = {Old yellow enzyme interferes with Bax-induced NADPH loss and lipid
peroxidation in yeast},
journal = {FEMS Yeast Research},
year = {2005},
volume = {5},
pages = {711--725},
number = {8},
month = may,
abstract = {The yeast transcriptional response to murine Bax expression was compared
with the changes induced by H2O2 treatment via microarray technology.
Although most of the Bax-responsive genes were also triggered by
H2O2 treatment, OYE3, ICY2, MLS1 and BTN2 were validated to have
a Bax-specific transcriptional response not shared with the oxidative
stress trigger. In knockout experiments, only deletion of OYE3, coding
for yeast Old yellow enzyme, attenuated the rate of Bax-induced growth
arrest, cell death and NADPH decrease. Lipid peroxidation was completely
absent in [Delta]OYE3 expressing Bax. However, the absence of OYE3
sensitized yeast cells to H2O2-induced cell death, and increased
the rate of NADPH decrease and lipid peroxidation. Our results clearly
indicate that OYE3 interferes with Bax- and H2O2-induced lipid peroxidation
and cell death in Saccharomyces cerevisiae.},
issn = {1567-1356},
keywords = {Old yellow enzyme, Bax, Cell death, Oxidative stress, NADPH decrease,
Lipid peroxidation},
url = {http://www.sciencedirect.com/science/article/B6W8C-4FDJ493-1/2/ef18e693e15f3bc7de0bf1b88582acca}
}
@ARTICLE{Reemers2009,
author = {Reemers, Sylvia S. and Groot Koerkamp, Marian J. and Holstege, Frank
C. and van Eden, Willem and Vervelde, Lonneke},
title = {Cellular host transcriptional responses to influenza A virus in chicken
tracheal organ cultures differ from responses in in vivo infected
trachea},
journal = {Veterinary Immunology and Immunopathology},
year = {2009},
volume = {132},
pages = {91--100},
number = {2-4},
month = dec,
abstract = {In this study a viral infection of a tissue culture model system was
compared to an in vivo infection, which is of importance to gauge
the utility of the model system. The aim was to characterize early
immune responses induced by avian influenza virus using tracheal
organ cultures (TOC) as a model system. First, the in vitro system
was optimized to ensure that the host transcription responses were
only influenced by virus infection and not by differences in viral
load. Upper and lower trachea both could be used in the cultures
because the virus load was the same. Cilia motility was not affected
in non-infected TOC and only slightly in infected TOC at 24 h post-inoculation.
Gene expression profiles of early immune responses were analyzed
in in vitro infected TOC, and were compared to the responses found
in in vivo infected trachea. The gene expression profile in infected
TOC suggested the up regulation of innate anti-viral responses that
were triggered by attachment, entry and uptake of virus leading to
several signalling cascades including NF-[kappa]B regulation. Genes
associated with IFN mediated responses were mainly type I IFN related.
Overlapping gene expression profiles between non-infected and infected
TOC suggested that tissue damage during excision induced wound healing
responses that masked early host responses to the virus. These responses
were confirmed by real-time quantitative RT-PCR showing up regulation
of IL-1[beta] and IL-6. Microarray analysis showed that gene expression
profiles of infected and non-infected TOC had a large overlap. This
overlap contained many immune-related genes associated with inflammatory
responses, apoptosis and immune system process and development. Infected
TOC and in vivo infected trachea shared few significantly differentially
expressed genes. The gene expression profile of infected TOC contained
fewer genes which were expressed at reduced amplitude of change.
Genes that were common between TOC and trachea were associated with
early immune responses likely triggered by virus attachment and entry.
Most of the genes were associated with IFN-mediated responses, mainly
type I IFN related. Our study implicates that although the TOC model
is suitable for culturing of virus and lectin or virus binding studies,
it is not suitable for measuring early immune responses upon viral
infection at host transcriptional level.},
issn = {0165-2427},
keywords = {Avian influenza virus, Organ culture, Host-pathogen interaction, Genomics,
Innate immunity},
url = {http://www.sciencedirect.com/science/article/B6TD5-4W6Y7WV-2/2/8778418bc7c02a2d5bb6c1c8eb84e9f9}
}
@ARTICLE{Reemers2009a,
author = {Reemers, Sylvia S. and van Haarlem, Daphne A. and Groot Koerkamp,
Marian J. and Vervelde, Lonneke},
title = {Differential gene-expression and host-response profiles against avian
influenza virus within the chicken lung due to anatomy and airflow},
journal = {J. Gen. Virol.},
year = {2009},
volume = {90},
pages = {2134--2146},
number = {9},
month = sep,
abstract = {Sampling the complete organ instead of defined parts might affect
analysis at both the cellular and transcriptional levels. We defined
host responses to H9N2 avian influenza virus (AIV) in trachea and
different parts of the lung. Chickens were spray-inoculated with
either saline or H9N2 AIV. Trachea and lung were sampled at 1 and
3 days post-inoculation (p.i.) for immunocytochemistry, real-time
quantitative RT-PCR and gene-expression profiling. The trachea was
divided into upper and lower parts and the lung into four segments,
according to anatomy and airflow. Two segments contained the primary
and secondary bronchi, cranial versus caudal (parts L1 and L3), and
two segments contained the tertiary bronchi, cranial versus caudal
(parts L2 and L4). Between the upper and lower trachea in both control
and infected birds, minor differences in gene expression and host
responses were found. In the lung of control birds, differences in
anatomy were reflected in gene expression, and in the lung of infected
birds, virus deposition enhanced the differences in gene expression.
Differential gene expression in trachea and lung suggested common
responses to a wide range of agents and site-specific responses.
In trachea, site-specific responses were related to heat shock and
lysozyme activity. In lung L1, which contained most virus, site-specific
responses were related to genes involved in innate responses, interleukin
activity and endocytosis. Our study indicates that the anatomy of
the chicken lung must be taken into account when investigating in
vivo responses to respiratory virus infections.},
url = {http://vir.sgmjournals.org/cgi/content/abstract/90/9/2134}
}
@ARTICLE{Reemers2010,
author = {Reemers, Sylvia S. and Jansen, Christine and Koerkamp, Marian J.
Groot and van Haarlem, Daphne and van de Haar, Peter and Degen, Winfried
G.J. and van Eden, Willem and Vervelde, Lonneke},
title = {Reduced immune reaction prevents immunopathology after challenge
with avian influenza virus: A transcriptomics analysis of adjuvanted
vaccines},
journal = {Vaccine},
year = {2010},
volume = {28},
pages = {6351--6360},
number = {38},
month = aug,
abstract = {To gain more insight in underlying mechanisms correlating to protection
against avian influenza virus (AIV) infection, we investigated correlates
of protection after AIV H9N2 infection and studied the contribution
of different adjuvants to a protective response at host transcriptional
level. One-day-old chickens were immunised with inactivated H9N2
supplemented with w/o, Al(OH)3, CpG or without adjuvant. Two weeks
later, birds were homologously challenged and at 1-4 days post challenge
(d.p.c.) trachea and lung were collected. Birds immunised with H9N2 + w/o
or H9N2 + Al(OH)3 were protected against challenge infection and
had lower viral RNA expression, less immune related genes induced
after challenge, a lower amplitude of change of gene expression and
smaller cellular influxes compared to the higher and prolonged gene
expression in unprotected birds. We show that a limited number of
differentially expressed genes correlates with reduced immune activation
and subsequently reduced immunopathology after challenge with AIV.},
issn = {0264-410X},
keywords = {Avian influenza virus, Vaccination, Microarray},
url = {http://www.sciencedirect.com/science/article/B6TD4-50HVYYS-6/2/54c80aee8e2d3bae909e3f0513376125}
}
@ARTICLE{Reemers2010a,
author = {Reemers, Sylvia S. and van Leenen, Dik and Groot Koerkamp, Marian
J. and van Haarlem, Daphne and van de Haar, Peter and van Eden, Willem
and Vervelde, Lonneke},
title = {Early host responses to avian influenza A virus are prolonged and
enhanced at transcriptional level depending on maturation of the
immune system},
journal = {Molecular Immunology},
year = {2010},
volume = {47},
pages = {1675--1685},
number = {9},
month = may,
abstract = {Newly hatched chickens are more susceptible to infectious diseases
than older birds because of an immature immune system. The aim of
this study was to determine to what extent host responses to avian
influenza virus (AIV) inoculation are affected by age. Therefore,
1- and 4-week (wk) old birds were inoculated with H9N2 AIV or saline.
The trachea and lung were sampled at 0, 8, 16 and 24 h post-inoculation
(h.p.i.) and gene expression profiles determined using microarray
analysis. Firstly, saline controls of both groups were compared to
analyse the changes in gene profiles related to development. In 1-wk-old
birds, higher expression of genes related to development of the respiratory
immune system and innate responses were found, whereas in 4-wk-old
birds genes were up regulated that relate to the presence of higher
numbers of leukocytes in the respiratory tract. After inoculation
with H9N2, gene expression was most affected at 16 h.p.i. in 1-wk-old
birds and at 16 and 24 h.p.i. in 4-wk-old birds in the trachea and
especially in the lung. In 1-wk-old birds less immune related genes
including innate related genes were induced which might be due to
age-dependent reduced functionality of antigen presenting cells (APC),
T cells and NK cells. In contrast cytokine and chemokines gene expression
was related to viral load in 1-wk-old birds and less in 4-wk-old
birds. Expression of cellular host factors that block virus replication
by interacting with viral factors was independent of age or tissue
for most host factors. These data show that differences in development
are reflected in gene expression and suggest that the strength of
host responses at transcriptional level may be a key factor in age-dependent
susceptibility to infection, and the cellular host factors involved
in virus replication are not.},
issn = {0161-5890},
keywords = {Influenza virus, Innate response, Age-dependent, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T9R-4YTM65P-1/2/bb7addec5108e44acc420323baeba354}
}
@ARTICLE{Reen2007,
author = {Reen, Rashmeet K. and Dombkowski, Alan A. and Kresty, Laura A. and
Cukovic, Daniela and Mele, Jennifer M. and Salagrama, Sridevi and
Nines, Ronald and Stoner, Gary D.},
title = {Effects of Phenylethyl Isothiocyanate on Early Molecular Events in
N-Nitrosomethylbenzylamine-Induced Cytotoxicity in Rat Esophagus},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {6484--6492},
number = {13},
month = jul,
abstract = {There is little information on early molecular events in the development
of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis
and of the effects of chemopreventive agents on these events. In
this study, we identified genes in rat esophagus that were differentially
expressed in response to short-term NMBA treatment and modulated
by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were
fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During
the 3rd week of dietary treatment, they were administered three s.c.
doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h
after the last treatment; esophagi were excised and processed for
histologic grading, microarray and real-time PCR analysis. Histopathologic
analysis showed that treatment of rats with PEITC had a protective
effect on NMBA-induced preneoplastic lesions in the rat esophagus.
We identified 2,261 genes that were differentially expressed in the
NMBA-treated versus control esophagi and 1,936 genes in the PEITC
+ NMBA versus NMBA-treated esophagi. The intersection of these two
sets resulted in the identification of 1,323 genes in NMBA-treated
esophagus, the vast majority of which were modulated by PEITC to
near-normal levels of expression. Measured changes in the expression
levels of eight selected genes were validated using real-time PCR.
Results from 12 microarrays indicated that PEITC treatment had a
genome-wide modulating effect on NMBA-induced gene expression. Samples
obtained from animals treated with PEITC alone or cotreated with
PEITC + NMBA were more similar to controls than to samples treated
with NMBA alone. [Cancer Res 2007;67(13):1-9]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/13/6484}
}
@ARTICLE{Reeve2009,
author = {Reeve, J. and Einecke, G. and Mengel, M. and Sis, B. and Kayser,
N. and Kaplan, B. and Halloran, P. F.},
title = {Diagnosing Rejection in Renal Transplants: A Comparison of Molecular-
and Histopathology-Based Approaches},
journal = {American Journal of Transplantation},
year = {2009},
volume = {9},
pages = {1802--1810},
number = {8},
abstract = {The transcriptome has considerable potential for improving biopsy
diagnoses. However, to realize this potential the relationship between
the molecular phenotype of disease and histopathology must be established.
We assessed 186 consecutive clinically indicated kidney transplant
biopsies using microarrays, and built a classifier to distinguish
rejection from nonrejection using predictive analysis of microarrays
(PAM). Most genes selected by PAM were interferon-γ—inducible
or cytotoxic T-cell associated, for example, CXCL9, CXCL11, GBP1
and INDO. We then compared the PAM diagnoses to those from histopathology,
which are based on the Banff diagnostic criteria. Disagreement occurred
in approximately 20% of diagnoses, principally because of idiosyncratic
limitations in the histopathology scoring system. The problematic
diagnosis of ‘borderline rejection’ was resolved by PAM into
two distinct classes, rejection and nonrejection. The diagnostic
discrepancies between Banff and PAM in these cases were largely due
to the Banff system's requirement for a tubulitis threshold in defining
rejection. By examining the discrepancies between gene expression
and histopathology, we provide external validation of the main features
of the histopathology diagnostic criteria (the Banff consensus system),
recommend improvements and outline a pathway for introducing molecular
measurements.},
issn = {1600-6143},
keywords = {Allograft rejection, Banff schema, microarrays, prediction},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1600-6143.2009.02694.x}
}
@ARTICLE{Reeves2009,
author = {Reeves, Felicity A and Chapple, Christopher R and Pullman, Mike},
title = {Success of acupuncture in the treatment of painful bladder syndrome
(interstitial cystitis)},
journal = {The Journal of Urology},
year = {2009},
volume = {181},
pages = {23--23},
number = {4, Supplement 1},
month = apr,
booktitle = {AUA Annual Meeting Program Abstracts, 2009 AUA Annual Meeting},
issn = {0022-5347},
url = {http://www.sciencedirect.com/science/article/B7XMT-4VTWN64-2C/2/1ca5e3b5188e0e269b5bd1cf7cf7f183}
}
@ARTICLE{Regala2008,
author = {Regala, Roderick P. and Thompson, E. Aubrey and Fields, Alan P.},
title = {Atypical Protein Kinase C{iota} Expression and Aurothiomalate Sensitivity
in Human Lung Cancer Cells},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {5888--5895},
number = {14},
month = jul,
abstract = {The antirheumatoid agent aurothiomalate (ATM) is a potent inhibitor
of oncogenic PKC{iota}. ATM inhibits non-small lung cancer (NSCLC)
growth by binding PKC{iota} and blocking activation of a PKC{iota}-Par6-Rac1-Pak-Mek
1,2-Erk 1,2 signaling pathway. Here, we assessed the growth inhibitory
activity of ATM in a panel of human cell lines representing major
lung cancer subtypes. ATM inhibited anchorage-independent growth
in all lines tested with IC50s ranging from [~]300 nmol/L to >100
{micro}mol/L. ATM sensitivity correlates positively with expression
of PKC{iota} and Par6, but not with the PKC{iota} binding protein
p62, or the proposed targets of ATM in rheumatoid arthritis (RA),
thioredoxin reductase 1 or 2. PKC{iota} expression profiling revealed
that a significant subset of primary NSCLC tumors express PKC{iota}
at or above the level associated with ATM sensitivity. ATM sensitivity
is not associated with general sensitivity to the cytotoxic agents
cis-platin, placitaxel, and gemcitabine. ATM inhibits tumorigenicity
of both sensitive and insensitive lung cell tumors in vivo at plasma
drug concentrations achieved in RA patients undergoing ATM therapy.
ATM inhibits Mek/Erk signaling and decreases proliferative index
without effecting tumor apoptosis or vascularization in vivo. We
conclude that ATM exhibits potent antitumor activity against major
lung cancer subtypes, particularly tumor cells that express high
levels of the ATM target PKC{iota} and Par6. Our results indicate
that PKC{iota} expression profiling will be useful in identifying
lung cancer patients most likely to respond to ATM therapy in an
ongoing clinical trial. [Cancer Res 2008;68(14):5888-95]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/14/5888}
}
@ARTICLE{Regassa2011,
author = {Regassa, A and Rings, F and Hoelker, M and Cinar, U and Tholen, E
and Looft, C and Schellander, K and Tesfaye, D},
title = {Transcriptome dynamics and molecular cross-talk between bovine oocyte
and its companion cumulus cells},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {57},
number = {1},
abstract = {BACKGROUND:The bi-directional communication between the oocyte and
its companion cumulus cells (CCs) is crucial for development and
functions of both cell types. Transcripts that are exclusively expressed
either in oocytes or CCs and molecular mechanisms affected due to
removal of the communication axis between the two cell types is not
investigated at a larger scale. The main objectives of this study
were: 1. To identify transcripts exclusively expressed either in
oocyte or CCs and 2. To identify those which are differentially expressed
when the oocyte is cultured with or without its companion CCs and
vice versa.RESULTS:We analyzed transcriptome profile of different
oocyte and CC samples using Affymetrix GeneChip Bovine Genome array
containing 23000 transcripts. Out of 13162 genes detected in germinal
vesicle (GV) oocytes and their companion CCs, 1516 and 2727 are exclusively
expressed in oocytes and CCs, respectively, while 8919 are expressed
in both. Similarly, of 13602 genes detected in metaphase II (MII)
oocytes and CCs, 1423 and 3100 are exclusively expressed in oocytes
and CCs, respectively, while 9079 are expressed in both. A total
of 265 transcripts are differentially expressed between oocytes cultured
with (OO + CCs) and without (OO - CCs) CCs, of which 217 and 48 are
over expressed in the former and the later groups, respectively.
Similarly, 566 transcripts are differentially expressed when CCs
mature with (CCs + OO) or without (CCs - OO) their enclosed oocytes.
Of these, 320 and 246 are over expressed in CCs + OO and CCs - OO,
respectively.While oocyte specific transcripts include those involved
in transcription (IRF6, POU5F1, MYF5, MED18), translation (EIF2AK1,
EIF4ENIF1) and CCs specific ones include those involved in carbohydrate
metabolism (HYAL1, PFKL, PYGL, MPI), protein metabolic processes
(IHH, APOA1, PLOD1), steroid biosynthetic process (APOA1, CYP11A1,
HSD3B1, HSD3B7). Similarly, while transcripts over expressed in OO
+ CCs are involved in carbohydrate metabolism (ACO1, 2), molecular
transport (GAPDH, GFPT1) and nucleic acid metabolism (CBS, NOS2),
those over expressed in CCs + OO are involved in cellular growth
and proliferation (FOS, GADD45A), cell cycle (HAS2, VEGFA), cellular
development (AMD1, AURKA, DPP4) and gene expression (FOSB, TGFB2).CONCLUSION:In
conclusion, this study has generated large scale gene expression
data from different oocyte and CCs samples that would provide insights
into gene functions and interactions within and across different
pathways that are involved in the maturation of bovine oocytes. Moreover,
the presence or absence of oocyte and CC factors during bovine oocyte
maturation can have a profound effect on transcript abundance of
each cell types, thereby showing the prevailing molecular cross-talk
between oocytes and their corresponding CCs.},
doi = {10.1186/1471-2164-12-57},
issn = {1471-2164},
pubmedid = {21261964},
url = {http://www.biomedcentral.com/1471-2164/12/57}
}
@ARTICLE{Rege2006,
author = {Rege, Kaushal and Pepsin, Mike and Falcon, Brandy and Steele, Landon
and Heng, Meng},
title = {High-throughput process development for recombinant protein purification},
journal = {Biotechnol. Bioeng.},
year = {2006},
volume = {93},
pages = {618--630},
number = {4},
abstract = {Abstract 10.1002/bit.20702.abs Methods development in chromatographic
purification processes is a complex operation and has traditionally
relied on trial and error approaches. The availability of a large
number of commercial media, choice of different modes of chromatography,
and diverse operating conditions contribute to the challenging task
of accelerating methods development. In this paper, we describe a
novel microtiter-plate based screening method to identify the appropriate
sequence of chromatographic steps that result in high purities of
bioproducts from their respective culture broths. Protein mixtures
containing the bioproduct were loaded on aliquots of different chromatographic
media in microtiter plates. Serial step elution of the proteins,
in concert with bioproduct-specific assays, resulted in the identification
of “active fractions� containing the bioproduct. The identification
of a successful chromatographic step was based on the purity of the
active fractions, which were then pooled and used as starting material
for screening the next chromatographic dimension. This procedure
was repeated across subsequent dimensions until single band purities
of the protein were obtained. The sequence of chromatographic steps
and the corresponding operating conditions identified from the screen
were validated under scaled-up conditions. Various modes of chromatography
including hydrophobic interaction, ion exchange (cation and anion
exchange) and hydrophobic charge-induction chromatography (HCIC),
and different operating conditions (pH, salt concentration and type,
etc.) were employed in the screen. This approach was employed to
determine the sequence of chromatographic steps for the purification
of recombinant α-amylase from its cell-free culture broth. Recommendations
from the screen resulted in single-band purity of the protein under
scaled-up conditions. Similar results were observed for an scFv-β-lactamase
fusion protein. The use of a miniaturized screen enables the parallel
screening of a wide variety of actual bioprocess media and conditions
and represents a novel paradigm approach for the high-throughput
process development of recombinant proteins. © 2005 Wiley Periodicals,
Inc.},
issn = {1097-0290},
keywords = {protein purification, methods development, process development, chromatography,
high-throughput screening, miniaturization, recombinant protein,
amylase, lactamase},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.20702}
}
@ARTICLE{Reggeti2008,
author = {Reggeti, F. and Bienzle, D.},
title = {Alloimmunity does not protect from challenge with the feline immunodeficiency
virus},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {124},
pages = {152--162},
number = {1-2},
month = jul,
abstract = {Immune responses against polymorphic host molecules incorporated into
lentiviral envelopes during cell budding have induced protection
against primate immunodeficiency virus infection. Dendritic cells
(DCs) express high levels of MHC molecules and are infectable by
lentiviruses. Therefore, in this pilot study we addressed the hypothesis
that immunization of cats with allogeneic DC would induce immune
responses that protect against challenge with the feline immunodeficiency
virus. Two groups of 3 cats each received 3 subcutaneous injections
of allogeneic or autologous DC, and were then challenged with viruses
propagated in the immunizing DC. Infection status and lymphocyte
parameters of cats were assessed during 6 weeks after challenge.
MHC II antigens were incorporated into viral particles as identified
by Western blot; and antibodies reactive with MHC class II antigens
were detected in the serum of cats immunized with allogeneic but
not autologous DC. After challenge, all cats had proviral DNA in
blood leukocytes from 2 weeks post-challenge onward and seroconverted.
Cats immunized with allogeneic DC maintained higher total and CD21+
lymphocyte concentrations, and higher CD4+/CD8+ lymphocyte ratios;
however, these differences were not significantly different from
cats that received autologous DC immunizations. Plasma viral load
was not significantly different between groups of cats (p = 0.204).
These results suggest that immunization of cats with allogeneic DC
does not induce protective immunity against FIV infection.},
issn = {0165-2427},
keywords = {Lentivirus, Dendritic cell, Alloimmunization, Cat, Retrovirus},
url = {http://www.sciencedirect.com/science/article/B6TD5-4S5KX7W-1/2/1bd7c082ba3800de29816d8e7d08b3fb}
}
@ARTICLE{RegiaSilvaSousa2011,
author = {Regia Silva Sousa, Katiene and Mauric Frossard Ribeiro, Andre and
Roberto Nunes Goes, Paulo and Eliza Facioni Guimaraes, Simone and
Lopes, Paulo Savio and Veroneze, Renata and Gasparino, Eliane},
title = {Toll-Like Receptor 6 differential expression in two pig genetic groups
vaccinated against Mycoplasma hyopneumoniae},
journal = {BMC Proceedings},
year = {2011},
volume = {5},
pages = {S9},
number = {Suppl 4},
abstract = {BACKGROUND:Mycoplasma hyopneumoniae is the etiologic agent of enzootic
pneumonia, which causes important economic losses to swine industry.
The Toll-like receptors (TLRs) are pattern-recognition receptors
which detect microbial presence and initiate the innate as well as
the adaptative immune defense. Toll-like receptor 6 is a type I transmembrane
protein that recognizes bacterial components. The aim of this study
was to compare mRNA expression pattern of TLR6 gene in two genetically
distinct groups of pigs vaccinated against Mycoplasma hyopneumoniae.METHODS:For
each genetic group, peripheral blood was collected just before and
10 days after vaccination from 10 Naturalized Brazilian Piau breed
and 10 Commercial White Line serum-negative female piglets. RNA was
extracted from peripheral blood mononuclear cells (PBMCs), reverse
transcripted and the qRT-PCR performed using SYBR green fluorescence
system, using GAPDH gene as endogenous control. Analyses were performed
by UNIVARIATE (Shapiro-Wilk test) and MIXED procedures of SAS software
(version 9.0).RESULTS:It was observed significant interaction between
breed and vaccination, being the TLR6 mRNA expression higher in the
Commercial White line than in the Piau breed after vaccination. Furthermore,
there was differential expression before and after vaccination in
the Commercial White line.CONCLUSIONS:Analysis of in TLR6 gene expression
showed difference between the two distinct genetic groups, however,
other TLRs gene expression must be evaluated for a better understanding
of innate resistance in the pig concerning Mycoplasma hyopneumoniae
infection.},
doi = {10.1186/1753-6561-5-S4-S9},
issn = {1753-6561},
url = {http://www.biomedcentral.com/1753-6561/5/S4/S9}
}
@ARTICLE{Regier2010,
author = {Regier, Nicole and Frey, Beat},
title = {Experimental comparison of relative RT-qPCR quantification approaches
for gene expression studies in poplar},
journal = {BMC Molecular Biology},
year = {2010},
volume = {11},
pages = {57},
number = {1},
abstract = {BACKGROUND:RT-qPCR is a powerful tool for analysing gene expression.
It depends on measuring the increase in fluorescence emitted by a
DNA-specific dye during the PCR reaction. For relative quantification,
where the expression of a target gene is measured in relation to
one or multiple reference genes, various mathematical approaches
are published. The results of relative quantification can be considerably
influenced by the chosen method.RESULTS:We quantified gene expression
of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the
roots of two black poplar clones, 58-861 and Poli, which were subjected
to drought stress. After proving the chosen reference genes actin
(ACT), elongation factor 1 (EF1) and ubiquitin (UBQ) to be constantly
expressed in the different watering regimes, we applied different
approaches for relative quantification to the same raw fluorescence
data. The results obtained using the comparative Cq method, LinRegPCR,
qBase software and the Pfaffl model showed a good correlation, whereas
calculation according to the Liu and Saint method produced highly
variable results. However, it has been shown that the most reliable
approach for calculation of the amplification efficiency is using
the mean increase in fluorescence during PCR in each individual reaction.
Accordingly, we could improve the quality of our results by applying
the mean amplification efficiencies for each amplicon to the Liu
and Saint method.CONCLUSIONS:As we could show that gene expression
results can vary depending on the approach used for quantification,
we recommend to carefully evaluate different quantification approaches
before using them in studies analysing gene expression.},
doi = {10.1186/1471-2199-11-57},
issn = {1471-2199},
pubmedid = {20701777},
url = {http://www.biomedcentral.com/1471-2199/11/57}
}
@ARTICLE{Regier2009,
author = {Regier, Nicole And Streb, Sebastian And Cocozza, Claudia And Schaub,
Marcus And Cherubini, Paolo And Zeeman, Samuel C. And Frey, Beat},
title = {Drought tolerance of two black poplar (Populus nigra L.) clones:
contribution of carbohydrates and oxidative stress defence},
journal = {Plant, Cell \& Environment},
year = {2009},
volume = {32},
pages = {1724--1736},
number = {12},
abstract = {ABSTRACT Drought is expected to become an increasingly important factor
limiting tree growth caused by climate change. Two divergent clones
of Populus nigra (58-861 and Poli) originating from contrasting environments
were subjected to water limitation (WL) to elucidate whether they
differ in tolerance to drought, which mechanisms to avoid stress
they exhibit and whether drought has an impact on the interactions
between roots and shoots. Limiting water availability caused photosynthetic
rate and total non-structural carbohydrate (TNC) levels to decrease
in 58-861. However, starch-degrading enzyme activity and gene expression
were induced in roots, and soluble sugar levels were higher than
in well-watered (WW) plants. These data suggest that assimilation
and partitioning of carbon to the roots are decreased, resulting
in mobilization of stored starch. In contrast, the photosynthetic
rate of Poli was reduced only late in the treatment, and carbohydrate
levels in WL plants were higher than in WW plants. Superoxide dismutase
(SOD) activity and gene expression were higher in Poli than in 58-861,
even in WW plants, leading to a higher capacity to defend against
oxidative stress.},
issn = {1365-3040},
keywords = {gene expression, leaf gas exchange, qRT-PCR, root, starch-degrading
enzymes, superoxide dismutase activity},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3040.2009.02030.x}
}
@ARTICLE{Regina2007,
author = {Regina, S. And Herault, O. And D'alteroche, L. And Binet, C. And
Gruel, Y.},
title = {JAK2 V617F is specifically associated with idiopathic splanchnic
vein thrombosis},
journal = {Journal of Thrombosis and Haemostasis},
year = {2007},
volume = {5},
pages = {859--861},
number = {4},
issn = {1538-7836},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1538-7836.2007.02384.x}
}
@ARTICLE{Regina2006,
author = {Regina, Sandra and Herault, Olivier and D'lteroche, Louis and Bacq,
Yannick and Domenenech, Jorge and Binet, Christian and Gruel, Yves},
title = {The JAK2 Mutation V617F Is Specifically Associated with Idiopathic
Splanchnic Vein Thrombosis.},
journal = {Blood (ASH Annual Meeting Abstracts)},
year = {2006},
volume = {108},
pages = {380--},
number = {11},
month = nov,
abstract = {Introduction Many risk factors have been identified in patients with
portal (PVT) and hepatic venous thrombosis (HVT), including myeloproliferative
disorders (MPD), i.e. polycythemia vera (PV) and essential thrombocythemia
(ET), with prevalence varying between 25% and 65%. Moreover, JAK2
mutation V617F has recently been detected in 65 to 97% of cases of
PV and 23 to 57% of ET. The aim of the present study was therefore
to evaluate the frequency of JAK2 mutation V617F in a cohort of consecutive
patients with PVT or HVT compared to a control group comprising patients
with deep vein thrombosis (DVT) of the lower limbs. Patients and
Methods Forty-four patients with PVT (n=42) or HVT (n=2) diagnosed
between 2001 and 2005, and 44 patients (matched for age and gender)
with idiopathic DVT were included. The presence of hereditary or
acquired risk factors for thrombosis (including FV Leiden and FII
G20210A polymorphism, defects in coagulation inhibitors, antiphospholipid
antibodies and hyperhomocysteinemia) was investigated in all patients.
Bone marrow (BM) biopsy and cultures of blood and BM progenitors
were performed in 18 patients with PVT for whom the etiology of thrombosis
was undefined. Screening for JAK2 mutation V617F was performed on
genomic DNA isolated from peripheral blood cells by an allele-specific
PCR and RFLP analysis using BsaXI, as previously described (Baxter
et al. Lancet 2005, 365:1054rft.jtitle=Lancetstitle=Lancetissn=0140-6736eissn=1474-547Xaulast=Baxterauinit1=E.+J.volume=365issue=9464spage=1054epage=1061atitle=Acquired+mutation+of+the+tyrosine+kinase+JAK2+in+human+myeloproliferative+disorders.2005-03-19id=info%3Apmid%2F15781101genre=articleval_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal),
combined with nano-electrophoresis (Bioanalyzer 2100, Agilent) to
increase sensitivity. HEL92.1.7 and HL60 cell lines were used as
positive and negative controls, respectively. Results The 2 groups
were similar in terms of blood count and conventional risk factors
for thrombosis (Table). JAK2 mutation V617F was detected in 8 patients
with PVT (18.2%) but in none with DVT (p=0.003). These 8 subjects
had normal blood counts, and no other acquired or hereditary risk
factor for thrombosis except for one case exhibiting moderate hyperhomocysteinemia.
Bone marrow was hyperplastic in 6/18 patients (all JAK2 V617F positive).
Cultures of progenitors showed endogenous erythroid formation in
6/18 cases (all JAK2 V617F positive). The clinical follow-up confirmed
the diagnosis of MPD (1 PV and 1 ET) in 2 patients. One subject died
in another context and blood counts have remained normal in the 5
other patients to date. The JAK2 mutation V617F was not detected
in any patient with negative bone marrow exploration (biopsy and
cultures). Conclusion The JAK2 mutation V617F is frequently and specifically
detected in patients with idiopathic PVT and no other risk factor
for thrombosis. Whether JAK2 mutation V617F should be screened in
all subjects with splanchnic vein thrombosis and should replace BM
biopsy and cultures warrants further studies. Biological data in
patients with PVT/HVT or DVT PVT or HVT (n=44) DVT (n=44) n % 95%
CI n % 95% CI p * FV Leiden 4 9.1 2.5-21.7 11 25 13.2-40.3 NS FII
20210A 10 22.7 11.5-37.8 6 13.6 5.2-27.4 NS AT, PC, PS deficiency
7 15.9 7.9-29.3 4 9.1 2.5-21.7 NS Antiphospholipid antibodies 5 11.4
4.9-24 8 18.2 9.5-32 NS Hyperhomocysteinemia 4 9.1 2.5-21.7 4 9.1
2.5-21.7 NS JAK2 V617 mutation 8 18.2 9.5-32 0 0 0-8 0.003 * Fisher
exact test},
url = {http://abstracts.hematologylibrary.org/cgi/content/abstract/108/11/380}
}
@ARTICLE{Rehm2011,
author = {Rehm, Armin and Mensen, Angela and Schradi, Kristina and Gerlach,
Kerstin and Wittstock, Stefanie and Winter, Susann and Buchner, Gilbert
and Dorken, Bernd and Lipp, Martin and Hopken, Uta E.},
title = {Cooperative function of CCR7 and lymphotoxin in the formation of
a lymphoma-permissive niche within murine secondary lymphoid organs},
journal = {Blood},
year = {2011},
volume = {118},
pages = {1020-1033},
number = {4},
abstract = {Lymphoma cell survival and progression are putatively dependent on
a specific microanatomic localization within secondary lymphoid organs.
Despite compelling data correlating homeostatic chemokine receptor
expression and human lymphoma pathogenesis, genetic models that either
mimic lymphoma dissemination or dissect a crosstalk of lymphoma and
stromal cells are missing. Applying the genetically tractable E{micro}-Myc
transgenic mouse model, we show that the chemokine receptor CCR7
regulates E{micro}-Myc lymphoma homing to lymph nodes and distinctive
microanatomic sites of the spleen. CCR7-controlled access of lymphoma
cells to the splenic T-cell zone led to a significant survival advantage
compared with CCR7-deficient lymphoma cells, which were excluded
from this zone. Within the niche, lymphoma cells stimulated a reciprocal
cross-talk with gp38+ fibroblastic reticular cells. This reciprocal
cooperation program was mediated by lymphoma B cell-presented lymphotoxin,
which acted on lymphotoxin-{beta}-receptor-bearing stromal cells
followed by alteration of stromal cellular composition. Cross-talk
inhibition by lymphotoxin- deletion and using a lymphotoxin-{beta}
receptor-immunoglobulin fusion protein impaired lymphoma growth.
Thus, abrogation of CCR7-governed migration and of sustained lymphotoxin
signaling could provide new targets in lymphoma therapy.},
doi = {10.1182/blood-2010-11-321265},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/4/1020.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/4/1020}
}
@ARTICLE{Rehman2010,
author = {Rehman, Atteeq Ur and Morell, Robert J. and Belyantseva, Inna A.
and Khan, Shahid Y. and Boger, Erich T. and Shahzad, Mohsin and Ahmed,
Zubair M. and Riazuddin, Saima and Khan, Shaheen N. and Riazuddin,
Sheikh and Friedman, Thomas B.},
title = {Targeted Capture and Next-Generation Sequencing Identifies C9orf75,
Encoding Taperin, as the Mutated Gene in Nonsyndromic Deafness DFNB79},
journal = {The American Journal of Human Genetics},
year = {2010},
volume = {86},
pages = {378--388},
number = {3},
month = mar,
abstract = {Targeted genome capture combined with next-generation sequencing was
used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3,
which includes 108 candidate genes. Genomic DNA from an affected
member of a consanguineous family segregating recessive, nonsyndromic
hearing loss was used to make a library of fragments covering the
DFNB79 linkage interval defined by genetic analyses of four pedigrees.
Homozygosity for eight previously unreported variants in transcribed
sequences was detected by evaluating a library of 402,554 sequencing
reads and was later confirmed by Sanger sequencing. Of these variants,
six were determined to be polymorphisms in the Pakistani population,
and one was in a noncoding gene that was subsequently excluded genetically
from the DFNB79 linkage interval. The remaining variant was a nonsense
mutation in a predicted gene, C9orf75, renamed TPRN. Evaluation of
the other three DFNB79-linked families identified three additional
frameshift mutations, for a total of four truncating alleles of this
gene. Although TPRN is expressed in many tissues, immunolocalization
of the protein product in the mouse cochlea shows prominent expression
in the taper region of hair cell stereocilia. Consequently, we named
the protein taperin.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4YDS2GW-2/2/d9ce2985ea34348794ab9893a40b8ebb}
}
@ARTICLE{Rehman2008,
author = {Rehman, Samrina and Salway, Fiona and Stanley, John K. and Ollier,
William E.R. and Day, Philip and Bayat, Ardeshir},
title = {Molecular Phenotypic Descriptors of Dupuytren's Disease Defined Using
Informatics Analysis of the Transcriptome},
journal = {The Journal of Hand Surgery},
year = {2008},
volume = {33},
pages = {359--372},
number = {3},
month = mar,
abstract = {Purpose Dupuytren's disease (DD) is a fibroproliferative disorder
of unknown etiopathogenesis, which may cause progressive, permanent
contracture of digits. Previous studies provide compelling evidence
that genetic alterations play an important role. Macroscopically
affected areas demonstrate phenotypic differences between the two
structurally distinct fibrotic elements in DD (ie, the nodule and
the cord). In this study, we set out to (1) compare gene expression
profiles between DD and transverse carpal fascia of control subjects
(external control); (2) profile DD cords and nodules from the palm
against the unaffected transverse palmar fascia (internal control);
and (3) identify biologically important candidate genes from the
transcriptome profiles.Methods RNA samples from DD nodules (n = 4),
cords (n = 4), and internal control (n = 4) as well as external control
(n = 4) from unaffected individuals were subjected to differential
gene expression profile analysis. Changes of more than 2-fold in
DD groups and controls were recorded. Quantitative reverse transcriptase-polymerase
chain reactions were performed to validate 16 implicated genes, which
included developmental control genes, matrix metalloproteinases,
and apoptotic genes.Results Several genes associated with DD formation
were common across all 6 pairwise analyses. Genes markedly upregulated
shared common expression levels across all pairwise analysis studies.
Pairs involving the DD nodule arrays were notably distinguishable
from all other permutations. The majority of genes dysregulated in
the DD cords demonstrated an increase in fold change when compared
with the DD nodule tissues. Key collagens, collagenases, metalloproteinases,
and inhibitors were identified. Genes involved in cytoskeleton development
and lipid metabolism were markedly dysregulated. Confirmations of
these alterations were obtained in quantitative reverse transcriptase-polymerase
chain reaction.Conclusions These data demonstrate a gradation in
expression of certain genes in DD tissue phenotypes compared with
control fascia. Transcriptome profiling is predictive not only of
disease but also of disease phenotype. These results indicate a number
of important candidate genes associated with DD formation, which
may provide clues for molecular mechanisms involved in DD pathogenesis.},
issn = {0363-5023},
keywords = {Cord, Dupuytren's disease/contracture, gene expression profiling,
nodule, Skoog's fibers, transcriptomics, transverse palmar fascia},
url = {http://www.sciencedirect.com/science/article/B6WJK-4S25G45-J/2/1aefb8a475567d41c4ec606dbd959e01}
}
@ARTICLE{Rehrauer2010,
author = {Rehrauer, Hubert and Aquino, Catharine and Gruissem, Wilhelm and
Henz, Stefan R. and Hilson, Pierre and Laubinger, Sascha and Naouar,
Naira and Patrignani, Andrea and Rombauts, Stephane and Shu, Huan
and Van de Peer, Yves and Vuylsteke, Marnik and Weigel, Detlef and
Zeller, Georg and Hennig, Lars},
title = {AGRONOMICS1: A New Resource for Arabidopsis Transcriptome Profiling},
journal = {Plant Physiology},
year = {2010},
volume = {152},
pages = {487--499},
number = {2},
month = feb,
abstract = {Transcriptome profiling has become a routine tool in biology. For
Arabidopsis (Arabidopsis thaliana), the Affymetrix ATH1 expression
array is most commonly used, but it lacks about one-third of all
annotated genes present in the reference strain. An alternative are
tiling arrays, but previous designs have not allowed the simultaneous
analysis of both strands on a single array. We introduce AGRONOMICS1,
a new Affymetrix Arabidopsis microarray that contains the complete
paths of both genome strands, with on average one 25mer probe per
35-bp genome sequence window. In addition, the new AGRONOMICS1 array
contains all perfect match probes from the original ATH1 array, allowing
for seamless integration of the very large existing ATH1 knowledge
base. The AGRONOMICS1 array can be used for diverse functional genomics
applications such as reliable expression profiling of more than 30,000
genes, detection of alternative splicing, and chromatin immunoprecipitation
coupled to microarrays (ChIP-chip). Here, we describe the design
of the array and compare its performance with that of the ATH1 array.
We find results from both microarrays to be of similar quality, but
AGRONOMICS1 arrays yield robust expression information for many more
genes, as expected. Analysis of the ATH1 probes on AGRONOMICS1 arrays
produces results that closely mirror those of ATH1 arrays. Finally,
the AGRONOMICS1 array is shown to be useful for ChIP-chip experiments.
We show that heterochromatic H3K9me2 is strongly confined to the
gene body of target genes in euchromatic chromosome regions, suggesting
that spreading of heterochromatin is limited outside of pericentromeric
regions.},
url = {http://www.plantphysiol.org/cgi/content/abstract/152/2/487}
}
@ARTICLE{Reich2011,
author = {Reich, Adrian and Klatsky, Peter and Carson, Sandra and Wessel, Gary},
title = {The Transcriptome of a Human Polar Body Accurately Reflects Its Sibling
Oocyte},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {40743-40749},
number = {47},
abstract = {Improved methods are needed to reliably and accurately evaluate oocyte
quality prior to fertilization and transfer into the woman of human
embryos created through in vitro fertilization (IVF). All oocytes
that are retrieved and matured in culture are exposed to sperm with
little in the way of evaluating the oocyte quality. Furthermore,
embryos created through IVF are currently evaluated for developmental
potential by morphology, a criterion lacking in quantitation and
accuracy. With the recent successes in oocyte vitrification and storage,
clear metrics are needed to determine oocyte quality prior to fertilizing.
The first polar body (PB) is extruded from the oocyte before fertilization
and can be biopsied without damaging the oocyte. Here, we tested
the hypothesis that the PB transcriptome is representative of that
of the oocyte. Polar body biopsy was performed on metaphase II (MII)
oocytes followed by single-cell transcriptome analysis of the oocyte
and its sibling PB. Over 12,700 unique mRNAs and miRNAs from the
oocyte samples were compared with the 5,431 mRNAs recovered from
the sibling PBs (5,256 shared mRNAs or 97%, including miRNAs). The
results show that human PBs reflect the oocyte transcript profile
and suggests that mRNA detection and quantification through high-throughput
quantitative PCR could result in the first molecular diagnostic for
gene expression in MII oocytes. This could allow for both oocyte
ranking and embryo preferences in IVF applications.},
doi = {10.1074/jbc.M111.289868},
eprint = {http://www.jbc.org/cgi/reprint/286/47/40743.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/47/40743}
}
@ARTICLE{Reich2005,
author = {Reich, Eva-Pia and Cui, Long and Yang, Lily and Pugliese-Sivo, Catherine
and Golovko, Andrei and Petro, Mary and Vassileva, Galya and Chu,
Inhou and Nomeir, Amin A. and Zhang, Li-Kang and Liang, Xian and
Kozlowski, Joseph A. and Narula, Satwant K. and Zavodny, Paul J.
and Chou, Chuan-Chu},
title = {Blocking ion channel KCNN4 alleviates the symptoms of experimental
autoimmune encephalomyelitis in mice},
journal = {Eur. J. Immunol.},
year = {2005},
volume = {35},
pages = {1027--1036},
number = {4},
abstract = {Abstract 10.1002/eji.200425954.abs The KCNN4 potassium-ion channel
has been reported to play an important role in regulating antigen-induced
T cell effector functions in vitro. This study presents the first
evidence that a selective KCNN4 blocker, TRAM-34, confers protection
against experimental autoimmune encephalomyelitis (EAE) in the mouse
model. Treatment with the KCNN4 blocker did not prevent infiltration
of T cells in the spinal cord, but resulted in the reduction of both
the protein and the message levels of TNF-α and IFN-γ as well as
the message levels of several other pro-inflammatory molecules in
the spinal cord. Plasma concentrations of TRAM-34 within a 24-h period
were between the in vitro IC50 and IC90 values for the KCNN4 channel.
The effect of TRAM-34 was reversible, as indicated by the development
of clinical EAE symptoms within 48 h after withdrawal of treatment.
In summary, our data support the idea that KCNN4 channels play a
critical role in the immune response during the development of MOG-induced
EAE in C57BL/6 mice. See accompanying Commentary: http://dx.doi.org/10.1002/eji.200526078},
issn = {1521-4141},
keywords = {Ion Channels, Cytokines, EAE},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200425954}
}
@ARTICLE{Reich2005a,
author = {Reich, Heather and Tritchler, David and Herzenberg, Andrew M. and
Kassiri, Zamaneh and Zhou, Xiaohua and Gao, Wei and Scholey, James
W.},
title = {Albumin Activates ERK Via EGF Receptor in Human Renal Epithelial
Cells},
journal = {J. Am. Soc. Nephrol.},
year = {2005},
volume = {16},
pages = {1266--1278},
number = {5},
month = may,
abstract = {Emerging clinical and experimental evidence strongly implicates proteinuria
in the progression of kidney disease. One pathway involves the activation
of NF{kappa}B by albumin, and it has been demonstrated that the activation
of NF{kappa}B induced by albumin is dependent on mitogen-activated
protein kinase ERK1/ERK2. To study the effect of albumin on gene
expression, primary human renal tubular cells were exposed in vitro
to albumin (1%) for 6 h, and gene expression profiling was performed
with the human oligonucleotide microarray, U133A Affymetrix Gene
Chip. In all, 223 genes were differentially regulated by albumin,
including marked upregulation of the EGF receptor (EGFR) and IL-8.
Accordingly, the authors sought to delineate the signaling pathway
linking albumin to the EGFR and activation of ERK1/ERK2. It was found
that albumin led to a dose- and time-dependent activation of ERK1/ERK2.
Treatment with albumin led to EGFR phosphorylation, but the activation
of ERK1/ERK2 was prevented by pretreatment of the cells with AG-1478,
the EGFR kinase inhibitor, at a dose that inhibited EGF-induced ERK1/ERK2
activation. Exogenously administered reactive oxygen species (ROS)
were found to activate ERK1/ERK2 via the EGFR and src tyrosine kinase
activity and pretreatment of cells with the antioxidant N-acetylcysteine
(NAC) and the NADPH oxidase inhibitor DPI abrogated albumin-induced
activation of ERK1/ERK2. The src tyrosine kinase inhibitor, PP2,
also inhibited the albumin-induced activation of ERK1/ERK2. Finally,
pretreatment with AG-1478, the MEK inhibitor UO126, and NAC prevented
the albumin-induced increase in IL-8 expression. The authors conclude
that the EGF receptor plays a central role in the signaling pathway
that links albumin to the activation of ERK1/ERK2 and increased expression
of IL-8. Gene profiling studies suggest that there may be a positive
feedback loop through the EGFR that amplifies the response of the
proximal tubule cell to albumin. Taken together, these results suggest
that the EGFR may be an important treatment target for kidney disease
associated with proteinuria.},
url = {http://jasn.asnjournals.org/cgi/content/abstract/16/5/1266}
}
@ARTICLE{Reichlen2010,
author = {Reichlen, Matthew J. and Murakami, Katsuhiko S. and Ferry, James
G.},
title = {Functional Analysis of the Three TATA Binding Protein Homologs in
Methanosarcina acetivorans},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {1511--1517},
number = {6},
month = mar,
abstract = {The roles of three TATA binding protein (TBP) homologs (TBP1, TBP2,
and TBP3) in the archaeon Methanosarcina acetivorans were investigated
by using genetic and molecular approaches. Although tbp2 and tbp3
deletion mutants were readily obtained, a tbp1 mutant was not obtained,
and the growth of a conditional tbp1 expression strain was tetracycline
dependent, indicating that TBP1 is essential. Transcripts of tbp1
were 20-fold more abundant than transcripts of tbp2 and 100- to 200-fold
more abundant than transcripts of tbp3, suggesting that TBP1 is the
primary TBP utilized during growth. Accordingly, tbp1 is strictly
conserved in the genomes of Methanosarcina species. {Delta}tbp3 and
{Delta}tbp2 strains exhibited an extended lag phase compared with
the wild type, although the lag phase for the {Delta}tbp2 strain
was less pronounced when this strain was transitioning from growth
on methylotrophic substrates to growth on acetate. Acetate-adapted
{Delta}tbp3 cells exhibited growth rates, final growth yields, and
lag times that were significantly reduced compared with those of
the wild type when the organisms were cultured with growth-limiting
concentrations of acetate, and the acetate-adapted {Delta}tbp2 strain
exhibited a final growth yield that was reduced compared with that
of the wild type when the organisms were cultured with growth-limiting
acetate concentrations. DNA microarray analyses identified 92 and
77 genes with altered transcription in the {Delta}tbp2 and {Delta}tbp3
strains, respectively, which is consistent with a role for TBP2 and
TBP3 in optimizing gene expression. Together, the results suggest
that TBP2 and TBP3 are required for efficient growth under conditions
similar to the conditions in the native environment of M. acetivorans.},
url = {http://jb.asm.org/cgi/content/abstract/192/6/1511}
}
@ARTICLE{Reichling2005,
author = {Reichling, Tim and Goss, Kathleen Heppner and Carson, Daniel J. and
Holdcraft, Robert W. and Ley-Ebert, Cathy and Witte, Dave and Aronow,
Bruce J. and Groden, Joanna},
title = {Transcriptional Profiles of Intestinal Tumors in ApcMin Mice are
Unique from those of Embryonic Intestine and Identify Novel Gene
Targets Dysregulated in Human Colorectal Tumors},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {166--176},
number = {1},
month = jan,
abstract = {The adenomatous polyposis coli (APC) tumor suppressor is a major regulator
of the Wnt signaling pathway in normal intestinal epithelium. APC,
in conjunction with AXIN and GSK-3{beta}, forms a complex necessary
for the degradation of {beta}-catenin, thereby preventing {beta}-catenin/T-cell
factor interaction and alteration of growth-controlling genes such
as c-MYC and cyclin D1. Inappropriate activation of the Wnt pathway,
via Apc/APC mutation, leads to gastrointestinal tumor formation in
both the mouse and human. In order to discover novel genes that may
contribute to tumor progression in the gastrointestinal tract, we
used cDNA microarrays to identify 114 genes with altered levels of
expression in ApcMin mouse adenomas from the duodenum, jejunum, and
colon. Changes in the expression of 24 of these 114 genes were not
observed during mouse development at embryonic day 16.5, postnatal
day 1, or postnatal day 14 (relative to normal adult intestine).
These 24 genes are not previously known Wnt targets. Seven genes
were validated by real-time reverse transcription-PCR analysis, whereas
four genes were validated by in situ hybridization to mouse adenomas.
Real-time reverse transcription-PCR analysis of human colorectal
cancer cell lines and adenocarcinomas revealed that altered expression
levels were also observed for six of the genes Igfbp5, Lcn2, Ly6d,
N4wbp4 (PMEPA1), S100c, and Sox4.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/1/166}
}
@ARTICLE{Reid2010,
author = {Reid, Scott M. and Pierce, Kenneth E. and Mistry, Rohit and Bharya,
Sukvinder and Dukes, Juliet P. and Volpe, Carmelo and Wangh, Lawrence
J. and King, Donald P.},
title = {Pan-serotypic detection of foot-and-mouth disease virus by RT linear-after-the-exponential
PCR},
journal = {Molecular and Cellular Probes},
year = {2010},
volume = {24},
pages = {250--255},
number = {5},
month = oct,
abstract = {A reverse transcription Linear-After-The-Exponential polymerase chain
reaction (RT LATE-PCR) assay was evaluated for detection of foot-and-mouth
disease virus (FMDV). This pan-serotypic assay targets highly conserved
sequences within the 3D (RNA polymerase) region of the FMDV genome,
and uses end-point hybridisation analysis of a single mismatch-tolerant
low temperature probe to confirm the identity of the amplicons. An
Armored RNA® served as an internal control to validate virus negative
results. The ability of the assay to identify FMDV was directly compared
to a real-time RT-PCR assay routinely used by reference laboratories.
The analytical sensitivity of the RT LATE-PCR assay was 10 genomic
copies and the dynamic range of the test was identical to real-time
RT-PCR based on decimal dilutions of an FMDV-positive sample. This
pan-serotypic assay was able to detect FMDV in a broad range of clinical
samples collected from field cases of FMD (n = 121), while samples
of other viruses causing vesicular disease in livestock and genetic
relatives of FMDV were negative. In addition to the laboratory-based
utility of this diagnostic test, the RT LATE-PCR assay format has
potential application for use in a portable ("point-of-care") device
designed to achieve rapid detection of FMDV in the field.},
issn = {0890-8508},
keywords = {Foot-and-mouth disease, RT LATE-PCR, Asymmetric PCR, Real-time RT-PCR,
Armored RNA},
url = {http://www.sciencedirect.com/science/article/B6WNC-4YYGGY2-1/2/de21d5e97a85187e183ece3c831231b1}
}
@ARTICLE{Reigstad2007,
author = {Reigstad, Christopher S. and Hultgren, Scott J. and Gordon, Jeffrey
I.},
title = {Functional Genomic Studies of Uropathogenic Escherichia coli and
Host Urothelial Cells when Intracellular Bacterial Communities Are
Assembled},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {21259--21267},
number = {29},
month = jul,
abstract = {Uropathogenic Escherichia coli (UPEC), the principal cause of urinary
tract infection in women, colonizes the gut as well as the genitourinary
tract. Studies of mice inoculated with UTI89, a sequenced isolate,
have revealed a complex life cycle that includes formation of intracellular
bacterial communities (IBCs) in bladder urothelial cells. To understand
how UPEC adapts to life in IBCs, we have used GeneChips and/or quantitative
reverse transcriptase PCR to study UTI89 recovered from the distal
gut of gnotobiotic mice and from IBCs harvested by laser capture
microdissection from the bladder urothelium of infected C3H/HeJ female
mice. Host responses were characterized in laser capture microdissected
urothelial cells that do or do not contain IBCs. The results reveal
components of ferric iron acquisition systems in UTI89 that are expressed
at significantly higher levels in IBCs compared with the intestine,
including the hemin receptor chuA (1,390 {+/-} 188-fold). Localized
urothelial responses to IBCs help oppose bacterial salvage of host
cell iron (e.g. up-regulation of Tfrc (transferrin receptor) and
Lcn2 (lipocalin 2)), facilitate glucose import (e.g. Hk2 (hexokinase
2)), and maintain epithelial structural integrity (e.g. Ivl (involucrin)
and Sbsn (suprabasin)). {Delta}chuA mutants produce significantly
smaller IBCs compared with wild type UTI89. This difference was not
observed in strains lacking sitA (ABC-type iron/manganese transporter
subunit), iroN (salmochelin receptor), hlyA ({alpha}-hemolysin),
or entF (enterobactin synthetase subunit). Together, these studies
indicate that heme- and siderophore-associated iron play key roles
in IBC development and provide a series of microbial and host biomarkers
for comparing UPEC strains isolated from humans.},
url = {http://www.jbc.org/cgi/content/abstract/282/29/21259}
}
@ARTICLE{Reijans2008,
author = {Reijans, Martin and Dingemans, Gijs and Klaassen, Corne H. and Meis,
Jacques F. and Keijdener, Judith and Mulders, Brit and Eadie, Kimberly
and van Leeuwen, Willem and van Belkum, Alex and Horrevorts, Alphons
M. and Simons, Guus},
title = {RespiFinder: a New Multiparameter Test To Differentially Identify
Fifteen Respiratory Viruses},
journal = {J. Clin. Microbiol.},
year = {2008},
volume = {46},
pages = {1232--1240},
number = {4},
month = apr,
abstract = {Broad-spectrum analysis for pathogens in patients with respiratory
tract infections is becoming more relevant as the number of potential
infectious agents is still increasing. Here we describe the new multiparameter
RespiFinder assay, which is based on the multiplex ligation-dependent
probe amplification (MLPA) technology. This assay detects 15 respiratory
viruses in one reaction. The MLPA reaction is preceded by a preamplification
step which ensures the detection of both RNA and DNA viruses with
the same specificity and sensitivity as individual monoplex real-time
reverse transcription-PCRs. The RespiFinder assay was validated with
144 clinical samples, and the results of the assay were compared
to those of cell culture and a respiratory syncytial virus (RSV)-specific
immunochromatography assay (ICA). Compared to the cell culture results,
the RespiFinder assay showed specificities and sensitivities of 98.2%
and 100%, respectively, for adenovirus; 96.4% and 100%, respectively,
for human metapneumovirus; 98.2% and 100%, respectively, for influenza
A virus (InfA); 99.1% and 100%, respectively, for parainfluenza virus
type 1 (PIV-1); 99.1% and 80%, respectively, for PIV-3; 90.1% and
100%, respectively, for rhinovirus; and 94.6% and 100%, respectively,
for RSV. Compared to the results of the RSV-specific ICA, the RespiFinder
assay gave a specificity and a sensitivity of 82.4% and 80%, respectively.
PIV-2, PIV-4, influenza B virus, InfA H5N1, and coronavirus 229E
were not detected in the clinical specimens tested. The use of the
RespiFinder assay resulted in an increase in the diagnostic yield
compared to that obtained by cell culture (diagnostic yields, 60%
and 35.5%, respectively). In conclusion, the RespiFinder assay provides
a user-friendly and high-throughput tool for the simultaneous detection
of 15 respiratory viruses with excellent overall performance statistics.},
url = {http://jcm.asm.org/cgi/content/abstract/46/4/1232}
}
@ARTICLE{Reilly2011,
author = {Reilly, S.-J. and Odeberg, J. and Tornvall, P.},
title = {Use of the Whole Leucocyte Population in the Study of the NFκB Pathway},
journal = {Scandinavian Journal of Immunology},
year = {2011},
volume = {73},
pages = {338--343},
number = {4},
abstract = {Abstract The nuclear factor NF-{kappa}B (NFκB) is involved in the
regulation of innate immunity and in particular, inflammatory genes.
It is associated with the pathogenesis of many chronic diseases such
as coronary heart disease (CHD). It is believed that individual susceptibility
to CHD might be affected by differences in gene transcription and
therefore gene expression in circulating cell populations such as
leucocytes is of interest. The aim of this study was to investigate
whether the total white blood cell population (leucocytes) could
be used to study the effect of lipopolysaccharide (LPS) treatment
on the expression of genes of the NFκB pathway. Gene expression
of the NFκB pathway was examined in total leucocyte, monocyte and
neutrophil populations. The majority of the 84 genes examined were
up-regulated after treatment with LPS for 12Â h in all cell populations
examined. The total leucocyte population behaved in a similar manner
to both neutrophils and monocytic cells, indicating that it alone
could be used in studies, therefore avoiding cell separation, which
is time-consuming and can result in cell activation. Furthermore,
in clinical studies, it enables a larger number of patient samples
to be studied simultaneously, while also reducing the amount of blood
required from each. This will provide enough starting material for
use with molecular techniques, such as chromatin immunoprecipitation
(ChIP) and ChIP-sequencing, and allow large-scale gene expression
studies of the NFκB pathway in patients with chronic and acute inflammation
with established CHD.},
doi = {10.1111/j.1365-3083.2011.02517.x},
issn = {1365-3083},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3083.2011.02517.x}
}
@ARTICLE{Reimer2011,
author = {Reimer, Michell M. and McQueen, Jamie and Searcy, Luke and Scullion,
Gillian and Zonta, Barbara and Desmazieres, Anne and Holland, Philip
R. and Smith, Jessica and Gliddon, Catherine and Wood, Emma R. and
Herzyk, Pawel and Brophy, Peter J. and McCulloch, James and Horsburgh,
Karen},
title = {Rapid Disruption of Axon-Glial Integrity in Response to Mild Cerebral
Hypoperfusion},
journal = {J. Neurosci.},
year = {2011},
volume = {31},
pages = {18185-18194},
number = {49},
abstract = {Myelinated axons have a distinct protein architecture essential for
action potential propagation, neuronal communication, and maintaining
cognitive function. Damage to myelinated axons, associated with cerebral
hypoperfusion, contributes to age-related cognitive decline. We sought
to determine early alterations in the protein architecture of myelinated
axons and potential mechanisms after hypoperfusion. Using a mouse
model of hypoperfusion, we assessed changes in proteins critical
to the maintenance of paranodes, nodes of Ranvier, axon-glial integrity,
axons, and myelin by confocal laser scanning microscopy. As early
as 3 d after hypoperfusion, the paranodal septate-like junctions
were damaged. This was marked by a progressive reduction of paranodal
Neurofascin signal and a loss of septate-like junctions. Concurrent
with paranodal disruption, there was a significant increase in nodal
length, identified by Nav1.6 staining, with hypoperfusion. Disruption
of axon-glial integrity was also determined after hypoperfusion by
changes in the spatial distribution of myelin-associated glycoprotein
staining. These nodal/paranodal changes were more pronounced after
1 month of hypoperfusion. In contrast, the nodal anchoring proteins
AnkyrinG and Neurofascin 186 were unchanged and there were no overt
changes in axonal and myelin integrity with hypoperfusion. A microarray
analysis of white matter samples indicated that there were significant
alterations in 129 genes. Subsequent analysis indicated alterations
in biological pathways, including inflammatory responses, cytokine-cytokine
receptor interactions, blood vessel development, and cell proliferation
processes. Our results demonstrate that hypoperfusion leads to a
rapid disruption of key proteins critical to the stability of the
axon-glial connection that is mediated by a diversity of molecular
events.},
doi = {10.1523/JNEUROSCI.4936-11.2011},
eprint = {http://www.jneurosci.org/cgi/reprint/31/49/18185.pdf},
url = {http://www.jneurosci.org/cgi/content/abstract/31/49/18185}
}
@ARTICLE{Reimers2005,
author = {Reimers, Mark and Heilig, Markus and Sommer, Wolfgang H.},
title = {Gene discovery in neuropharmacological and behavioral studies using
Affymetrix microarray data},
journal = {Methods},
year = {2005},
volume = {37},
pages = {219--228},
number = {3},
month = nov,
abstract = {We describe methods and software tools for doing data analysis based
on Affymetrix microarray data, emphasizing often neglected issues.
In our experience with neuroscience studies, experimental design
and quality assessment are vital. We also describe in detail the
pre-processing methods we have found useful for Affymetrix data.
Finally, we summarize the statistical literature and describe some
pitfalls in the post-processing analysis.},
booktitle = {Chip Technology in Neuroscience},
issn = {1046-2023},
keywords = {Brain, Expression microarray, Regional hybridization bias, Statistical
analysis},
url = {http://www.sciencedirect.com/science/article/B6WN5-4HMF7H7-3/2/1f73ad4660f14a20768704c0ece6004f}
}
@ARTICLE{Reinders2009,
author = {Reinders, Jon},
title = {Amplification of Bisulfite-Converted DNA for Genome-Wide DNA Methylation
Profiling},
journal = {Cold Spring Harb Protoc},
year = {2009},
volume = {2009},
pages = {pdb.prot5342--},
number = {12},
month = dec,
abstract = {DNA methylation, in which cytosine is modified to form 5-methylcytosine,
is a well-characterized epigenetic modification essential for normal
development in plants and mammals. Aberrant DNA methylation patterns
have been implicated in disease development, notably cancer. It is
therefore important to develop genome-wide DNA methylation profiling
technology. In this article, I describe a bisulfite methylation profiling
(BiMP) method for assessing DNA methylation patterns. Treatment of
DNA with sodium bisulfite converts unmethylated cytosine to uracil,
whereas 5-methylcytosine is not converted. During subsequent polymerase
chain reaction (PCR) amplification, uracil amplifies as thymine,
whereas 5-methylcytosine amplifies as cytosine, thereby creating
C-to-T transitions. Although single base detection of DNA methylation
patterns provided by bisulfite conversion is clearly advantageous,
there are inherent challenges associated with this approach. Successful
conversion requires relatively high temperatures (50{degrees}C-60{degrees}C)
and low pH (5.2), both of which may result in a high degree of DNA
fragmentation. Also, whole genome amplification methods established
for genomic DNA have resulted in poor reproducibility when applied
to bisulfite-converted DNA. The protocol described here mitigates
these adverse effects and provides bisulfite-converted DNA suitable
for genome-wide DNA methylation profiling using array-based analysis
platforms.},
url = {http://cshprotocols.cshlp.org/cgi/content/abstract/2009/12/pdb.prot5342}
}
@ARTICLE{Reinders2008,
author = {Reinders, Jon and Delucinge Vivier, Celine and Theiler, Gregory and
Chollet, Didier and Descombes, Patrick and Paszkowski, Jerzy},
title = {Genome-wide, high-resolution DNA methylation profiling using bisulfite-mediated
cytosine conversion},
journal = {Genome Res.},
year = {2008},
volume = {18},
pages = {469--476},
number = {3},
month = mar,
abstract = {Methylation of cytosines (mC) is essential for epigenetic gene regulation
in plants and mammals. Aberrant mC patterns are associated with heritable
developmental abnormalities in plants and with cancer in mammals.
We have developed a genome-wide DNA methylation profiling technology
employing a novel amplification step for DNA subjected to bisulfite-mediated
cytosine conversion. The methylation patterns detected are not only
consistent with previous results obtained with mC immunoprecipitation
(mCIP) techniques, but also demonstrated improved resolution and
sensitivity. The technology, named BiMP (for Bisulfite Methylation
Profiling), is more cost-effective than mCIP and requires as little
as 100 ng of Arabidopsis DNA.},
url = {http://genome.cshlp.org/cgi/content/abstract/18/3/469}
}
@ARTICLE{Reindl2009,
author = {Reindl, Katie M and Kittilson, Jeffrey D and Sheridan, Mark A},
title = {Differential ligand binding and agonist-induced regulation characteristics
of the two rainbow trout GH receptors, Ghr1 and Ghr2, in transfected
cells},
journal = {J. Endocrinol.},
year = {2009},
volume = {202},
pages = {463--471},
number = {3},
month = sep,
abstract = {Previously, we isolated and characterized two distinct GH receptor
(GHR)-encoding mRNAs, ghr1 and ghr2, from rainbow trout. In this
study, Chinese hamster ovary-K1 cells were individually transfected
with plasmids that contained cDNAs encoding rainbow trout ghr1 or
ghr2. High affinity binding of 125I-salmonid GH (sGH) by the expressed
receptors was saturable, displaceable, and ligand selective. Whole-cell
binding analysis revealed a single class of binding site; for Ghr1
Kd=8 nM, for Ghr2 Kd=17 nM. While salmonid prolactin (sPrl) displaced
125I-sGH from both Ghr1 and Ghr2, the affinity of either receptor
subtype for sPrl was substantially less than for sGH; salmonid somatolactin,
another member of the GH-PRL family, did not displace labeled sGH
except at pharmacological concentrations. 125I-sGH was internalized
by Ghr1- and Ghr2-expressing cells in a time-dependent manner; the
maximum internalization reached was 71% for Ghr1 and 55% for Ghr2.
Long-term exposure (24 h) of transfected cells to sGH up-regulated
surface expression of both Ghr1 and Ghr2; however, sGH induced surface
expression of Ghr1 to a greater extent than that of Ghr2. These results
indicate that rainbow trout ghrs display both overlapping and distinct
characteristics that may be important for ligand selection and differential
action in target organs.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/202/3/463}
}
@ARTICLE{Reiner2008,
author = {Reiner, David S. and Ankarklev, Johan and Troell, Karin and Palm,
Daniel and Bernander, Rolf and Gillin, Frances D. and Andersson,
Jan O. and Svärd, Staffan G.},
title = {Synchronisation of Giardia lamblia: Identification of cell cycle
stage-specific genes and a differentiation restriction point},
journal = {International Journal for Parasitology},
year = {2008},
volume = {38},
pages = {935--944},
number = {8-9},
month = jul,
abstract = {The intestinal parasite Giardia lamblia undergoes cell differentiations
that entail entry into and departure from the replicative cell cycle.
The pathophysiology of giardiasis depends directly upon the ability
of the trophozoite form to replicate in the host upper small intestine.
Thus, cell proliferation is tightly linked to disease. However, studies
of cell cycle regulation in Giardia have been hampered by the inability
to synchronise cultures. Here we report that Giardia isolates of
the major human genotypes A and B can be synchronised using aphidicolin,
a mycotoxin that reversibly inhibits replicative DNA polymerases
in eukaryotic cells. Aphidicolin arrests Giardia trophozoites in
the early DNA synthesis (S) phase of the cell cycle. We identified
a set of cell cycle orthologues in the Giardia genome using bioinformatic
analyses and showed that synchronised parasites express these genes
in a cell cycle stage-specific manner. The synchronisation method
also showed that during encystation, exit from the ordinary cell
cycle occurs preferentially in G2 and defines a restriction point
for differentiation. Synchronisation opens up possibilities for further
molecular and cell biological studies of chromosome replication,
mitosis and segregation of the complex cytoskeleton in Giardia.},
issn = {0020-7519},
keywords = {Aphidicolin, Cell cycle, Cyclin, DNA replication, Encystation, Parasite},
url = {http://www.sciencedirect.com/science/article/B6T7F-4RM7N2R-1/2/fe65452a011c3df4edf0e21524dedfbc}
}
@ARTICLE{Reinert2011,
author = {Reinert, Thomas and Modin, Charlotte and Castano, Francisco M. and
Lamy, Philippe and Wojdacz, Tomasz K. and Hansen, Lise Lotte and
Wiuf, Carsten and Borre, Michael and Dyrskjot, Lars and Orntoft,
Torben F.},
title = {Comprehensive Genome Methylation Analysis in Bladder Cancer: Identification
and Validation of Novel Methylated Genes and Application of These
as Urinary Tumor Markers},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {5582-5592},
number = {17},
abstract = {Purpose: Epigenetic alterations are common and can now be addressed
in a parallel fashion. We investigated the methylation in bladder
cancer with respect to location in genome, consistency, variation
in metachronous tumors, impact on transcripts, chromosomal location,
and usefulness as urinary markers. Experimental Design: A microarray
assay was utilized to analyze methylation in 56 samples. Independent
validation was conducted in 63 samples by a PCR-based method and
bisulfite sequencing. The methylation levels in 174 urine specimens
were quantified. Transcript levels were analyzed using expression
microarrays and pathways were analyzed using dedicated software.
Results: Global methylation patterns were established within and
outside CpG islands. We validated methylation of the eight tumor
markers genes ZNF154 (P < 0.0001), HOXA9 (P < 0.0001), POU4F2 (P
< 0.0001), EOMES (P = 0.0005), ACOT11 (P = 0.0001), PCDHGA12 (P =
0.0001), CA3 (P = 0.0002), and PTGDR (P = 0.0110), the candidate
marker of disease progression TBX4 (P < 0.04), and other genes with
stage-specific methylation. The methylation of metachronous tumors
was stable and targeted to certain pathways. The correlation to expression
was not stringent. Chromosome 21 showed most differential methylation
(P < 0.0001) and specifically hypomethylation of keratins, which
together with keratin-like proteins were epigenetically regulated.
In DNA from voided urine, we detected differential methylation of
ZNF154 (P < 0.0001), POU4F2 (P < 0.0001), HOXA9 (P < 0.0001), and
EOMES (P < 0.0001), achieving 84% sensitivity and 96% specificity.
Conclusions: We initiated a detailed mapping of the methylome in
metachronous bladder cancer. Novel genes with tumor, chromosome,
as well as pathway-specific differential methylation in bladder cancer
were identified. The methylated genes were promising cancer markers
for early detection of bladder cancer. Clin Cancer Res; 17(17); 5582-92.
(C)2011 AACR.},
doi = {10.1158/1078-0432.CCR-10-2659},
eprint = {http://clincancerres.aacrjournals.org/cgi/reprint/17/17/5582.pdf},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/17/5582}
}
@ARTICLE{Reiniger2010,
author = {Reiniger, Nina and Lau, Kai and McCalla, Daren and Eby, Bonnie and
Cheng, Bin and Lu, Yan and Qu, Wu and Quadri, Nosirudeen and Ananthakrishnan,
Radha and Furmansky, Maryana and Rosario, Rosa and Song, Fei and
Rai, Vivek and Weinberg, Alan and Friedman, Richard and Ramasamy,
Ravichandran and D'Agati, Vivette and Schmidt, Ann Marie},
title = {Deletion of the Receptor for Advanced Glycation End Products Reduces
Glomerulosclerosis and Preserves Renal Function in the Diabetic OVE26
Mouse},
journal = {Diabetes},
year = {2010},
volume = {59},
pages = {2043--2054},
number = {8},
month = aug,
abstract = {OBJECTIVEPrevious studies showed that genetic deletion or pharmacological
blockade of the receptor for advanced glycation end products (RAGE)
prevents the early structural changes in the glomerulus associated
with diabetic nephropathy. To overcome limitations of mouse models
that lack the progressive glomerulosclerosis observed in humans,
we studied the contribution of RAGE to diabetic nephropathy in the
OVE26 type 1 mouse, a model of progressive glomerulosclerosis and
decline of renal function. RESEARCH DESIGN AND METHODSWe bred OVE26
mice with homozygous RAGE knockout (RKO) mice and examined structural
changes associated with diabetic nephropathy and used inulin clearance
studies and albumin:creatinine measurements to assess renal function.
Transcriptional changes in the Tgf-{beta}1 and plasminogen activator
inhibitor 1 gene products were measured to investigate mechanisms
underlying accumulation of mesangial matrix in OVE26 mice. RESULTSDeletion
of RAGE in OVE26 mice reduced nephromegaly, mesangial sclerosis,
cast formation, glomerular basement membrane thickening, podocyte
effacement, and albuminuria. The significant 29% reduction in glomerular
filtration rate observed in OVE26 mice was completely prevented by
deletion of RAGE. Increased transcription of the genes for plasminogen
activator inhibitor 1, Tgf-{beta}1, Tgf-{beta}-induced, and {alpha}1-(IV)
collagen observed in OVE26 renal cortex was significantly reduced
in OVE26 RKO kidney cortex. ROCK1 activity was significantly lower
in OVE26 RKO compared with OVE26 kidney cortex. CONCLUSIONSThese
data provide compelling evidence for critical roles for RAGE in the
pathogenesis of diabetic nephropathy and suggest that strategies
targeting RAGE in long-term diabetes may prevent loss of renal function.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/59/8/2043}
}
@ARTICLE{Reis2011,
author = {Reis, Patricia and Waldron, Levi and Goswami, Rashmi and Xu, Wei
and Xuan, Yali and Perez-Ordonez, Bayardo and Gullane, Patrick and
Irish, Jonathan and Jurisica, Igor and Kamel-Reid, Suzanne},
title = {mRNA transcript quantification in archival samples using multiplexed,
color-coded probes.},
journal = {BMC Biotechnology},
year = {2011},
volume = {11},
pages = {46},
number = {1},
abstract = {BACKGROUND:A recently developed probe-based technology, the NanoString
nCounterTM gene expression system, has been shown to allow accurate
mRNA transcript quantification using low amounts of total RNA. We
assessed the ability of this technology for mRNA expression quantification
in archived formalin-fixed, paraffin-embedded (FFPE) oral carcinoma
samples.RESULTS:We measured mRNA transcript abundance of 20 genes
(COL3A1, COL4A1, COL5A1, COL5A2, CTHRC1, CXCL1, CXCL13, MMP1, P4HA2,
PDPN, PLOD2, POSTN, SDHA, SERPINE1, SERPINE2, SERPINH1, THBS2, TNC,
GAPDH, RPS18) in 38 samples (19 paired fresh-frozen and FFPE oral
carcinoma tissues, archived from 1997-2008) by both NanoString and
SYBR Green I fluorescent dye-based quantitative real-time PCR (RQ-PCR).
We compared gene expression data obtained by NanoString vs. RQ-PCR
in both fresh-frozen and FFPE samples. Fresh-frozen samples showed
a good overall Pearson correlation of 0.78, and FFPE samples showed
a lower overall correlation coefficient of 0.59, which is likely
due to sample quality. We found a higher correlation coefficient
between fresh-frozen and FFPE samples analyzed by NanoString (r=0.90)
compared to fresh-frozen and FFPE samples analyzed by RQ-PCR (r=0.50).
In addition, NanoString data showed a higher mean correlation (r=0.94)
between individual fresh-frozen and FFPE sample pairs compared to
RQ-PCR (r=0.53).CONCLUSIONS:Based on our results, we conclude that
both technologies are useful for gene expression quantification in
fresh-frozen or FFPE tissues; however, the probe-based NanoString
method achieved superior gene expression quantification results when
compared to RQ-PCR in archived FFPE samples. We believe that this
newly developed technique is optimal for large-scale validation studies
using total RNA isolated from archived, FFPE samples.},
doi = {10.1186/1472-6750-11-46},
issn = {1472-6750},
pubmedid = {21549012},
url = {http://www.biomedcentral.com/1472-6750/11/46}
}
@ARTICLE{Reis-Filho2006,
author = {Reis-Filho, Jorge Sergio and Simpson, Pete T. and Turner, Nicholas
C. and Lambros, Maryou Ballo and Jones, Chris and Mackay, Alan and
Grigoriadis, Anita and Sarrio, David and Savage, Kay and Dexter,
Tim and Iravani, Marjan and Fenwick, Kerry and Weber, Barbara and
Hardisson, David and Schmitt, Fernando Carlos and Palacios, Jose
and Lakhani, Sunil R. and Ashworth, Alan},
title = {FGFR1 Emerges as a Potential Therapeutic Target for Lobular Breast
Carcinomas},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {6652--6662},
number = {22},
month = nov,
abstract = {Purpose: Classic lobular carcinomas (CLC) account for 10% to 15% of
all breast cancers. At the genetic level, CLCs show recurrent physical
loss of chromosome16q coupled with the lack of E-cadherin (CDH1 gene)
expression. However, little is known about the putative therapeutic
targets for these tumors. The aim of this study was to characterize
CLCs at the molecular genetic level and identify putative therapeutic
targets. Experimental Design: We subjected 13 cases of CLC to a comprehensive
molecular analysis including immunohistochemistry for E-cadherin,
estrogen and progesterone receptors, HER2/neu and p53; high-resolution
comparative genomic hybridization (HR-CGH); microarray-based CGH
(aCGH); and fluorescent and chromogenic in situ hybridization for
CCND1 and FGFR1. Results: All cases lacked the expression of E-cadherin,
p53, and HER2, and all but one case was positive for estrogen receptors.
HR-CGH revealed recurrent gains on 1q and losses on 16q (both, 85%).
aCGH showed a good agreement with but higher resolution and sensitivity
than HR-CGH. Recurrent, high level gains at 11q13 (CCND1) and 8p12-p11.2
were identified in seven and six cases, respectively, and were validated
with in situ hybridization. Examination of aCGH and the gene expression
profile data of the cell lines, MDA-MB-134 and ZR-75-1, which harbor
distinct gains of 8p12-p11.2, identified FGFR1 as a putative amplicon
driver of 8p12-p11.2 amplification in MDA-MB-134. Inhibition of FGFR1
expression using small interfering RNA or a small-molecule chemical
inhibitor showed that FGFR1 signaling contributes to the survival
of MDA-MB-134 cells. Conclusions: Our findings suggest that receptor
FGFR1 inhibitors may be useful as therapeutics in a subset of CLCs.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/22/6652}
}
@ARTICLE{Reiser2009,
author = {Reiser, Peter J. and Bicer, Sabahattin and Chen, Qun and Zhu, Ling
and Quan, Ning},
title = {Masticatory (`superfast') myosin heavy chain and embryonic/atrial
myosin light chain 1 in rodent jaw-closing muscles},
journal = {J. Exp. Biol.},
year = {2009},
volume = {212},
pages = {2511--2519},
number = {16},
month = aug,
abstract = {Masticatory myosin is widely expressed among several vertebrate classes.
Generally, the expression of masticatory myosin has been associated
with high bite force for a carnivorous feeding style (including capturing/restraining
live prey), breaking down tough plant material and defensive biting
in different species. Masticatory myosin expression in the largest
mammalian order, Rodentia, has not been reported. Several members
of Rodentia consume large numbers of tree nuts that are encased in
very hard shells, presumably requiring large forces to access the
nutmeat. We, therefore, tested whether some rodent species express
masticatory myosin in jaw-closing muscles. Myosin isoform expression
in six Sciuridae species was examined, using protein gel electrophoresis,
immunoblotting, mass spectrometry and RNA analysis. The results indicate
that masticatory myosin is expressed in some Sciuridae species but
not in other closely related species with similar diets but having
different nut-opening strategies. We also discovered that the myosin
light chain 1 isoform associated with masticatory myosin heavy chain,
in the same four Sciuridae species, is the embryonic/atrial isoform.
We conclude that rodent speciation did not completely eliminate masticatory
myosin and that its persistent expression in some rodent species
might be related to not only diet but also to feeding style.},
url = {http://jeb.biologists.org/cgi/content/abstract/212/16/2511}
}
@ARTICLE{Reiser2011,
author = {Reiser, Vladimir and Smith, Ryan C. and Xue, Jiyan and Kurtz, Marc
M. and Liu, Rong and LeGrand, Cheryl and He, Xuanmin and Yu, Xiang
and Wong, Peggy and Hinchcliffe, John S. and Tanen, Michael R. and
Lazar, Gloria and Zieba, Renata and Ichetovkin, Marina and Chen,
Zhu and O'Neill, Edward A. and Tanaka, Wesley K. and Marton, Matthew
J. and Liao, Jason and Morris, Mark and Hailman, Eric and Tokiwa,
George Y. and Plump, Andrew S.},
title = {High-Throughput Simultaneous Analysis of RNA, Protein, and Lipid
Biomarkers in Heterogeneous Tissue Samples},
journal = {Clin. Chem.},
year = {2011},
volume = {57},
pages = {1545-1555},
number = {11},
abstract = {BACKGROUNDWith expanding biomarker discovery efforts and increasing
costs of drug development, it is critical to maximize the value of
mass-limited clinical samples. The main limitation of available methods
is the inability to isolate and analyze, from a single sample, molecules
requiring incompatible extraction methods. Thus, we developed a novel
semiautomated method for tissue processing and tissue milling and
division (TMAD). METHODSWe used a SilverHawk atherectomy catheter
to collect atherosclerotic plaques from patients requiring peripheral
atherectomy. Tissue preservation by flash freezing was compared with
immersion in RNAlater(R), and tissue grinding by traditional mortar
and pestle was compared with TMAD. Comparators were protein, RNA,
and lipid yield and quality. Reproducibility of analyte yield from
aliquots of the same tissue sample processed by TMAD was also measured.
RESULTSThe quantity and quality of biomarkers extracted from tissue
prepared by TMAD was at least as good as that extracted from tissue
stored and prepared by traditional means. TMAD enabled parallel analysis
of gene expression (quantitative reverse-transcription PCR, microarray),
protein composition (ELISA), and lipid content (biochemical assay)
from as little as 20 mg of tissue. The mean correlation was r = 0.97
in molecular composition (RNA, protein, or lipid) between aliquots
of individual samples generated by TMAD. We also demonstrated that
it is feasible to use TMAD in a large-scale clinical study setting.
CONCLUSIONSThe TMAD methodology described here enables semiautomated,
high-throughput sampling of small amounts of heterogeneous tissue
specimens by multiple analytical techniques with generally improved
quality of recovered biomolecules.},
doi = {10.1373/clinchem.2010.157743},
eprint = {http://www.clinchem.org/cgi/reprint/57/11/1545.pdf},
url = {http://www.clinchem.org/cgi/content/abstract/57/11/1545}
}
@ARTICLE{Reiss2008,
author = {Reiss, David J. and Facciotti, Marc T. and Baliga, Nitin S.},
title = {Model-based deconvolution of genome-wide DNA binding},
journal = {Bioinformatics},
year = {2008},
volume = {24},
pages = {396--403},
number = {3},
month = feb,
abstract = {Motivation: Chromatin immunoprecipitation followed by hybridization
to a genomic tiling microarray (ChIP-chip) is a routinely used protocol
for localizing the genomic targets of DNA-binding proteins. The resolution
to which binding sites in this assay can be identified is commonly
considered to be limited by two factors: (1) the resolution at which
the genomic targets are tiled in the microarray and (2) the large
and variable lengths of the immunoprecipitated DNA fragments. Results:
We have developed a generative model of binding sites in ChIP-chip
data and an approach, MeDiChI, for efficiently and robustly learning
that model from diverse data sets. We have evaluated MeDiChI's performance
using simulated data, as well as on several diverse ChIP-chip data
sets collected on widely different tiling array platforms for two
different organisms (Saccharomyces cerevisiae and Halobacterium salinarium
NRC-1). We find that MeDiChI accurately predicts binding locations
to a resolution greater than that of the probe spacing, even for
overlapping peaks, and can increase the effective resolution of tiling
array data by a factor of 5x or better. Moreover, the method's performance
on simulated data provides insights into effectively optimizing the
experimental design for increased binding site localization accuracy
and efficacy. Availability: MeDiChI is available as an open-source
R package, including all data, from http://baliga.systemsbiology.net/medichi.
Contact: dreiss@systemsbiology.org Supplementary information: Supplementary
data are available at Bioinformatics online.},
url = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/3/396}
}
@ARTICLE{Reiter2005,
author = {Reiter, Ali K. and Crozier, Stephen J. and Kimball, Scot R. and Jefferson,
Leonard S.},
title = {Meal Feeding Alters Translational Control of Gene Expression in Rat
Liver},
journal = {J. Nutr.},
year = {2005},
volume = {135},
pages = {367--375},
number = {3},
month = mar,
abstract = {Meal feeding after a period of food deprivation results in a subsequent
increase in the protein and RNA content of the liver. To gain insight
into the mechanisms involved in the response to food intake, changes
in the association of selected mRNAs with polysomes were examined.
On the day of the study, rat livers were collected at 0, 15, 60,
and 180 min after the start of feeding and analyzed for biomarkers
of the translational control of protein synthesis. Protein synthesis
was increased within 60 min and was sustained for 180 min. Assembly
of the active eukaryotic initiation factor (eIF) 4F complex was elevated
within 15 min, as indicated by the relative association of eIF4E
{middle dot} eIF4G, but returned to the basal value within 180 min.
Phosphorylation of the ribosomal protein (rp) S6 kinase S6K1 and
its substrate rpS6 was increased within 15 min and was sustained
for at least 180 min. Both eIF4F assembly and activation of S6K1
have been linked to upregulated translation of a subset of mRNAs.
To identify translationally regulated mRNAs, polysomal (i.e., actively
translated) and nonpolysomal (nontranslated) fractions were isolated
and subjected to microarray analysis. The mRNAs encoding 78 proteins,
including 42 proteins involved in protein synthesis, exhibited increased
abundance in polysomes in response to feeding. Overall, the results
demonstrate that protein synthesis as well as ribosomal protein mRNA
translation undergo rapid and sustained stimulation in the liver
after meal feeding and thus contribute to the previously observed
increases in protein and RNA content.},
url = {http://jn.nutrition.org/cgi/content/abstract/135/3/367}
}
@ARTICLE{Reiter2011,
author = {Reiter, M. and Kirchner, B. and Muller, H. and Holzhauer, C. and
Mann, W. and Pfaffl, M. W.},
title = {Quantification noise in single cell experiments},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {e124},
number = {18},
abstract = {In quantitative single-cell studies, the critical part is the low
amount of nucleic acids present and the resulting experimental variations.
In addition biological data obtained from heterogeneous tissue are
not reflecting the expression behaviour of every single-cell. These
variations can be derived from natural biological variance or can
be introduced externally. Both have negative effects on the quantification
result. The aim of this study is to make quantitative single-cell
studies more transparent and reliable in order to fulfil the MIQE
guidelines at the single-cell level. The technical variability introduced
by RT, pre-amplification, evaporation, biological material and qPCR
itself was evaluated by using RNA or DNA standards. Secondly, the
biological expression variances of GAPDH, TNF, IL-1{beta}, TLR4 were
measured by mRNA profiling experiment in single lymphocytes. The
used quantification setup was sensitive enough to detect single standard
copies and transcripts out of one solitary cell. Most variability
was introduced by RT, followed by evaporation, and pre-amplification.
The qPCR analysis and the biological matrix introduced only minor
variability. Both conducted studies impressively demonstrate the
heterogeneity of expression patterns in individual cells and showed
clearly today's limitation in quantitative single-cell expression
analysis.},
doi = {10.1093/nar/gkr505},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/18/e124.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/18/e124}
}
@ARTICLE{Reiter2007,
author = {Reiter, Martina and Walf, Vanessa M. and Christians, Arne and Pfaffl,
Michael W. and Meyer, Heinrich H.D.},
title = {Modification of mRNA expression after treatment with anabolic agents
and the usefulness for gene expression-biomarkers},
journal = {Analytica Chimica Acta},
year = {2007},
volume = {586},
pages = {73--81},
number = {1-2},
month = mar,
abstract = {With this feasibility study a first step towards a new monitoring
system for hormonal treatments was done. Screening of regulation
and function of anabolic sex steroids via modified gene expression
of mRNA in various tissues could be a new approach to trace treatments
with unknown drugs or newly combined cocktails. In the study, uterus,
liver and muscle tissue from 24 cycling heifers were taken after
the animals were treated either with Melengestrol Acetate (MGA),
Finaplix-H® (200 mg Trenbolone Acetate) or Ralgro® (36 mg Zeranol)
for 56 days. In every treatment group always two heifers were given
1-fold, 3-fold and 10-fold doses of the standard preparation, the
control group without any treatment consisted of two animals. The
different tissue gene expression profiles were investigated via the
candidate gene approach. Totally 57 candidate genes were selected
according to their functionality by screening the actual literature
and composed to functional groups: angiogenesis, apoptosis, cell
cycle, endocrine factors, energy metabolism, inflammatory factors,
muscle function, oncogenes, protein metabolism and transcription
factors. Gene expression was measured using quantitative real-time
RT-PCR (qRT-PCR) technology. From 24 tested candidate genes in the
liver, 17 showed a significant regulation. Eight genes were influenced
by MGA, 9 by Finaplix-H®, and 4 by Ralgro®. For the muscle tissue
19 genes were tested with the result that in the neck muscle 11 genes
were regulated and in the hind limb muscle 8 genes. In the neck 5
genes were affected by MGA, 6 by Finaplix-H® and 3 by Ralgro®. Only
2 genes were influenced by MGA in the hind limb muscle. Finaplix-H®
affected 6 and Ralgro® 4 genes. In the uterus 29 target genes were
tested and 13 were significantly influenced by the anabolic sex steroids.
Under Finaplix-H® treatment eight target genes were regulated and
Ralgro® and MGA showed a significant regulation in four target genes.
The highest gene expression changes under anabolic treatment were
observed in the uterus. The analyzed genes showed significant regulations
but further studies, testing different animal husbandry conditions
will be needed to identify meaningful expression patterns for the
different tissues. With the investigation of the regulation and possible
function of anabolic sex steroids via gene expression, a preparatory
work for the development of an expression pattern for drug screening
was made.},
booktitle = {Papers Presented at the 5th International Symposium on Hormone and
Veterinary Drug Residue Analysis, Papers Presented at the 5th International
Symposium on Hormone and Veterinary drug Residue Analysis},
issn = {0003-2670},
keywords = {Anabolic agents, Expression profiling, Candidate gene approach, Melengestrol
acetat, Trenbolone acetat, Zeranol, Real-time quantitative reverse
transcriptase polymerase chain reaction},
url = {http://www.sciencedirect.com/science/article/B6TF4-4M93KDK-8/2/3c883014ff6f252fe5391c19ff6c33c7}
}
@ARTICLE{Reith2009,
author = {Reith, Frank and Etschmann, Barbara and Grosse, Cornelia and Moors,
Hugo and Benotmane, Mohammed A. and Monsieurs, Pieter and Grass,
Gregor and Doonan, Christian and Vogt, Stefan and Lai, Barry and
Martinez-Criado, Gema and George, Graham N. and Nies, Dietrich H.
and Mergeay, Max and Pring, Allan and Southam, Gordon and Brugger,
Joel},
title = {Mechanisms of gold biomineralization in the bacterium Cupriavidus
metallidurans},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {17757--17762},
number = {42},
month = oct,
abstract = {While the role of microorganisms as main drivers of metal mobility
and mineral formation under Earth surface conditions is now widely
accepted, the formation of secondary gold (Au) is commonly attributed
to abiotic processes. Here we report that the biomineralization of
Au nanoparticles in the metallophillic bacterium Cupriavidus metallidurans
CH34 is the result of Au-regulated gene expression leading to the
energy-dependent reductive precipitation of toxic Au(III)-complexes.
C. metallidurans, which forms biofilms on Au grains, rapidly accumulates
Au(III)-complexes from solution. Bulk and microbeam synchrotron X-ray
analyses revealed that cellular Au accumulation is coupled to the
formation of Au(I)-S complexes. This process promotes Au toxicity
and C. metallidurans reacts by inducing oxidative stress and metal
resistances gene clusters (including a Au-specific operon) to promote
cellular defense. As a result, Au detoxification is mediated by a
combination of efflux, reduction, and possibly methylation of Au-complexes,
leading to the formation of Au(I)-C-compounds and nanoparticulate
Au0. Similar particles were observed in bacterial biofilms on Au
grains, suggesting that bacteria actively contribute to the formation
of Au grains in surface environments. The recognition of specific
genetic responses to Au opens the way for the development of bioexploration
and bioprocessing tools.},
url = {http://www.pnas.org/cgi/content/abstract/106/42/17757}
}
@ARTICLE{Reitmair2010,
author = {Reitmair, Armin and Lambrecht, Nils W. G. and Yakubov, Iskandar and
Nieves, Amelia and Old, David and Donde, Yariv and Dinh, Danny and
Burk, Robert and Sachs, George and Im, Wha Bin and Wheeler, Larry},
title = {Prostaglandin E2 receptor subtype EP2- and EP4-regulated gene expression
profiling in human ciliary smooth muscle cells},
journal = {Physiol Genomics},
year = {2010},
volume = {42},
pages = {348--360},
number = {3},
month = aug,
abstract = {Prostanoids are an important class of intraocular pressure (IOP)-lowering
antiglaucoma agents that act primarily via increased uveo-scleral
aqueous humor outflow through the ciliary body. We have developed
two novel PGE2 analogs that are specific agonists for the PGE2 receptor
subtypes EP2 and EP4, respectively. To identify gene regulatory networks
and key players that mediate the physiological effects observed in
vivo, we performed genomewide expression studies using human ciliary
smooth muscle cells. Quantitative real-time RT-PCR confirmed a largely
overlapping gene expression profile subsequent to EP2 and EP4 agonist
treatment, with 65 significantly regulated genes identified overall,
5 being specific for the EP2 agonist and 6 specific for the EP4 agonist.
We found predicted functional cAMP-response elements in promoter
regions of a large fraction of the predominantly upregulated genes,
which suggests that the cAMP signaling pathway is the most important
intracellular signaling pathway for these agonists in these cells.
Several target genes were identified that, as part of complex regulatory
networks, are implicated in tissue remodeling processes and osmoregulation
(e.g., AREG, LOXL3, BMP2, AQP3) and thus may help elucidate the mechanism
of action of these IOP-lowering drugs involving the uveo-scleral
outflow path.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42/3/348}
}
@ARTICLE{Reitz2011,
author = {Reitz, Christiane and Tokuhiro, Shinya and Clark, Lorraine N. and
Conrad, Christopher and Vonsattel, Jean-Paul and Hazrati, Lili-Naz
and Palotás, András and Lantigua, Raphael and Medrano, Martin and
Z. Jiménez -Velázquez, Ivonne and Vardarajan, Badri and Simkin,
Irene and Haines, Jonathan L. and Pericak -Vance, Margaret A. and
Farrer, Lindsay A. and Lee, Joseph H. and Rogaeva, Ekaterina and
George- Hyslop, Peter St. and Mayeux, Richard},
title = {SORCS1 alters amyloid precursor protein processing and variants may
increase Alzheimer's disease risk},
journal = {Annals of Neurology},
year = {2011},
volume = {69},
pages = {47--64},
number = {1},
abstract = {Abstract Objective:Sorting mechanisms that cause the amyloid precursor
protein (APP) and the β-secretases and γ-secretases to colocalize
in the same compartment play an important role in the regulation
of Aβ production in Alzheimer's disease (AD). We and others have
reported that genetic variants in the Sortilin-related receptor (SORL1)
increased the risk of AD, that SORL1 is involved in trafficking of
APP, and that underexpression of SORL1 leads to overproduction of
Aβ. Here we explored the role of one of its homologs, the sortilin-related
VPS10 domain containing receptor 1 (SORCS1), in AD.Methods:We analyzed
the genetic associations between AD and 16 SORCS1–single nucleotide
polymorphisms (SNPs) in 6 independent data sets (2,809 cases and
3,482 controls). In addition, we compared SorCS1 expression levels
of affected and unaffected brain regions in AD and control brains
in microarray gene expression and real-time polymerase chain reaction
(RT-PCR) sets, explored the effects of significant SORCS1-SNPs on
SorCS1 brain expression levels, and explored the effect of suppression
and overexpression of the common SorCS1 isoforms on APP processing
and Aβ generation.Results:Inherited variants in SORCS1 were associated
with AD in all datasets (0.001 < p< 0.049). In addition, SorCS1 influenced
APP processing. While overexpression of SorCS1 reduced γ-secretase
activity and Aβ levels, the suppression of SorCS1 increased γ-secretase
processing of APP and the levels of Aβ.Interpretations:These data
suggest that inherited or acquired changes in SORCS1 expression or
function may play a role in the pathogenesis of AD. Ann Neurol 2011;69:47–64.},
doi = {10.1002/ana.22308},
issn = {1531-8249},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ana.22308}
}
@ARTICLE{Rekik2008,
author = {Rekik, Imen and Salimonti, Amelia and Grati Kamoun, Naziha and Muzzalupo,
Innocenzo and Lepais, Oliver and Gerber, Sophie and Perri, Enzo and
Rebai, Ahmed},
title = {Characterization and Identification of Tunisian Olive Tree Varieties
by Microsatellite Markers},
journal = {HortScience},
year = {2008},
volume = {43},
pages = {1371--1376},
number = {5},
month = aug,
abstract = {In the Mediterranean basin, a large number of olive varieties are
present. This poses a series of problems concerning germplasm characterization
and management. In addition, there is a problem arising from the
existence of homonyms and synonyms. This makes cultivar identification
very difficult and complex. Microsatellites or simple sequence repeat
(SSR) are locus-specific codominant markers showing a high degree
of polymorphism and multiple alleles per locus. Their high informativeness
makes them the markers of choice in genetic diversity studies. This
work presents the results of molecular characterization and identification
of 20 Tunisian olive varieties using 10 SSR markers. All the SSR
amplification products were sequenced to determine the number of
repeats and the range of allele size. The number of alleles per SSR
varied from three to six and the average heterozygosity rate ranged
from 30% to 95%. Hierarchical classification of varieties base on
similarity measures and clustering was globally consistent with the
grouping of varieties by end use and phenotypic characteristics.
The result is that varieties having the same name were found to have
a clonal relationship. Paternity analysis showed also clone relationships
between varieties not known to be related.},
url = {http://hortsci.ashspublications.org/cgi/content/abstract/43/5/1371}
}
@ARTICLE{Rekik2011,
author = {Rekik, Wiem and Dufort, Isabelle and Sirard, Marc-André},
title = {Analysis of the gene expression pattern of bovine blastocysts at
three stages of development},
journal = {Molecular Reproduction and Development},
year = {2011},
volume = {78},
pages = {226--240},
number = {4},
abstract = {Abstract Blastocyst formation is a primordial event of pre-implantation
development since it is required for pregnancy establishment and
progression. The blastocyst plays a pivotal role because it is the
stage at which the embryo starts coordinated cross-talk with the
mother. It is also the terminal step before transfer in bovine; it
reflects all stresses the embryo may have faced during the process
of in vitro treatment. Achieving the formation of a morphologically
healthy blastocyst following normal kinetics is good, but remains
a poor indicator of embryo quality. Considering the limitation of
the invasive methods for competence assessment, the analysis of blastocysts'
gene expression is a promising way to improve our understanding of
blastocyst formation and to study the effects of different treatments
on gene expression. To that end, early, expanded, and hatched blastocysts,
derived from in vitro fertilization and culture, were collected for
RNA extraction, amplification, and cDNA microarray hybridization.
Gene candidates (IFNt, PLAC8, SSLP1, AKR1B1, HNRNPA2B1, ARGFX, NANOS,
CCNB1) were selected and confirmed using real-time RT-PCR to validate
the microarray data. Our analysis showed that hatched blastocysts
are enriched in transcripts implicated in attachment, cell adhesion,
and extracellular matrix digestion. Early blastocysts expressed genes
mainly involved in cell cycle control, transcription, and translation.
Real-time RT-PCR validated most microarray results (87.5%). Overall,
our study provides new insights into the molecular regulation of
blastocyst formation. In addition, it could help assess blastocyst
staging and select better embryos based on the expression of quality
markers. Mol. Reprod. Dev. 78:226–240, 2011. © 2011 Wiley-Liss,
Inc.},
doi = {10.1002/mrd.21286},
issn = {1098-2795},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mrd.21286}
}
@ARTICLE{Remke2009,
author = {Remke, Marc and Pfister, Stefan and Kox, Corinne and Toedt, Grischa
and Becker, Natalia and Benner, Axel and Werft, Wiebke and Breit,
Stephen and Liu, Shuangyou and Engel, Felix and Wittmann, Andrea
and Zimmermann, Martin and Stanulla, Martin and Schrappe, Martin
and Ludwig, Wolf-Dieter and Bartram, Claus R. and Radlwimmer, Bernhard
and Muckenthaler, Martina U. and Lichter, Peter and Kulozik, Andreas
E.},
title = {High-resolution genomic profiling of childhood T-ALL reveals frequent
copy-number alterations affecting the TGF-{beta} and PI3K-AKT pathways
and deletions at 6q15-16.1 as a genomic marker for unfavorable early
treatment response},
journal = {Blood},
year = {2009},
volume = {114},
pages = {1053--1062},
number = {5},
month = jul,
abstract = {Precursor T-cell acute lymphoblastic leukemia (T-ALL) in children
represents a clinical challenge, because relapses are usually fatal.
It is thus necessary to identify high-risk patients as early as possible
to effectively individualize treatment. We aimed to define novel
molecular risk markers in T-ALL and performed array-based comparative
genomic hybridization (array-CGH) and expression analyses in 73 patients.
We show that DNA copy-number changes are common in T-ALL and affect
70 of 73 (96%) patients. Notably, genomic imbalances predicted to
down-regulate the TGF-{beta} or up-regulate the PI3K-AKT pathways
are identified in 25 of 73 (34%) and 21 of 73 (29%) patients, suggesting
that these pathways play key roles in T-ALL leukemogenesis. Furthermore,
we identified a deletion at 6q15-16.1 in 9 of 73 (12%) of the patients,
which predicts poor early treatment response. This deletion includes
the CASP8AP2 gene, whose expression is shown to be down-regulated.
The interaction of CASP8AP2 with CASP8 plays a crucial role in apoptotic
regulation, suggesting a functional link between the clinical effect
of the deletion and the molecular mode of action. The data presented
here implicate the TGF-{beta} and PI3K-AKT pathways in T-ALL leukemogenesis
and identify a subgroup of patients with CASP8AP2 deletions and poor
early treatment response.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/5/1053}
}
@ARTICLE{Remondini2006,
author = {Remondini, Daniel and Nylund, Reetta and Reivinen, Jukka and Poulletier
de Gannes, Florence and Veyret, Bernard and Lagroye, Isabelle and
Haro, Emmanuelle and Trillo, M. Angeles and Capri, Miriam and Franceschi,
Claudio and Schlatterer, Kathrin and Gminski, Richard and Fitzner,
Rudolf and Tauber, Rudolf and Schuderer, Jurgen and Kuster, Niels
and Leszczynski, Dariusz and Bersani, Ferdinando and Maercker, Christian},
title = {Gene expression changes in human cells after exposure to mobile phone
microwaves},
journal = {Proteomics},
year = {2006},
volume = {6},
pages = {4745--4754},
number = {17},
abstract = {Abstract Possible biological effects of mobile phone microwaves were
investigated in vitro. In this study, which was part of the 5FP
EU project REFLEX (Risk Evaluation of Potential Environmental Hazards
From Low-Energy Electromagnetic Field Exposure Using Sensitive in vitro
Methods), six human cell types, immortalized cell lines and primary
cells, were exposed to 900 and 1800 MHz. RNA was isolated from
exposed and sham-exposed cells and labeled for transcriptome analysis
on whole-genome cDNA arrays. The results were evaluated statistically
using bioinformatics techniques and examined for biological relevance
with the help of different databases. NB69 neuroblastoma cells, T lymphocytes,
and CHME5 microglial cells did not show significant changes in gene
expression. In EA.hy926 endothelial cells, U937 lymphoblastoma
cells, and HL-60 leukemia cells we found between 12 and 34 up-
or down-regulated genes. Analysis of the affected gene families does
not point towards a stress response. However, following microwave
exposure, some but not all human cells might react with an increase
in expression of genes encoding ribosomal proteins and therefore
up-regulating the cellular metabolism.},
issn = {1615-9861},
keywords = {Bioinformatics, Mobile phones, Radiofrequency electromagnetic fields,
Transcriptome analysis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200500896}
}
@ARTICLE{Remoe2011,
author = {Remø, S.C. and Olsvik, P.A. and Torstensen, B.E. and Amlund, H. and
Breck, O. and Waagbø, R.},
title = {Susceptibility of Atlantic salmon lenses to hydrogen peroxide oxidation
ex vivo after being fed diets with vegetable oil and methylmercury},
journal = {Experimental Eye Research},
year = {2011},
volume = {92},
pages = {414--424},
number = {5},
month = may,
abstract = {The development of cataract in farmed Atlantic salmon (Salmo salar
L.) has been related to changes in feed composition resulting in
sub-optimal lens nutrition. The present study was performed to investigate
the ability of Atlantic salmon lenses to withstand oxidative stress
ex vivo, with focus on the nutritional lipid history and exposure
to methylmercury (MeHg) as a relevant dietary contaminant. Since
dietary histidine has been shown to have a mitigating effect on the
prevalence of cataract in farmed salmon, the antioxidative abilities
of histidine and NAH, a major imidazole in the salmon lens, was also
investigated ex vivo. Lenses from Atlantic salmon prefed diets based
on either fish oil (FO) or vegetable oil (VO) as lipid source, with
or without addition of 5 mg MeHg kg-1 feed, were cultured for 96 h
in normal medium (control), medium added 5 mM H2O2 or in histidine
enriched medium. Lipid class composition of the lenses was not affected
by the dietary lipids; while VO fed fish had a decrease in lens n - 3/n - 6
fatty acid ratio due to minor but significant increase in the concentration
of 18:2 n - 6 and 20:4 n - 6, and decrease in 20:5 n - 3 fatty acids
compared to FO fed fish. The lenses accumulated mercury in response
to dietary levels, but neither the oxidative status nor any physiological
responses were affected. The cultured lenses responded to H2O2 exposure
with loss of transparency, accumulation of auto-fluorescent compounds,
volume increase and reduced glutathione concentration similarly and
irrespective of the dietary history. Lenses extracted histidine from
the media, and synthesised NAH during the culture period. The innate
antioxidative defence system appeared to be influenced both by the
dietary lipid history and histidine enrichment on a transcriptional
level. Catalase and SPARC were expressed higher in lenses from FO
fed fish, and glutaredoxin showed elevated expression levels in FO
lenses cultured in histidine enriched medium, suggesting that histidine
is related to the innate antioxidant defence in salmon lenses. Further,
the concentration of NAH was significantly reduced in oxidatively
stressed lenses. Based on the results from this study it is suggested
that NAH has a novel role as antioxidant in the Atlantic salmon lens.},
issn = {0014-4835},
keywords = {Atlantic salmon, cataract, antioxidants, N-acetyl-histidine, lens
culture, vegetable oil, methylmercury},
url = {http://www.sciencedirect.com/science/article/pii/S0014483511000753}
}
@ARTICLE{Ren2005,
author = {Ren, Dacheng and Zuo, Rongjun and Gonzalez Barrios, Andres F. and
Bedzyk, Laura A. and Eldridge, Gary R. and Pasmore, Mark E. and Wood,
Thomas K.},
title = {Differential Gene Expression for Investigation of Escherichia coli
Biofilm Inhibition by Plant Extract Ursolic Acid},
journal = {Appl. Envir. Microbiol.},
year = {2005},
volume = {71},
pages = {4022--4034},
number = {7},
month = jul,
abstract = {After 13,000 samples of compounds purified from plants were screened,
a new biofilm inhibitor, ursolic acid, has been discovered and identified.
Using both 96-well microtiter plates and a continuous flow chamber
with COMSTAT analysis, 10 {micro}g of ursolic acid/ml inhibited Escherichia
coli biofilm formation 6- to 20-fold when added upon inoculation
and when added to a 24-h biofilm; however, ursolic acid was not toxic
to E. coli, Pseudomonas aeruginosa, Vibrio harveyi, and hepatocytes.
Similarly, 10 {micro}g of ursolic acid/ml inhibited biofilm formation
by >87% for P. aeruginosa in both complex and minimal medium and
by 57% for V. harveyi in minimal medium. To investigate the mechanism
of this nontoxic inhibition on a global genetic basis, DNA microarrays
were used to study the gene expression profiles of E. coli K-12 grown
with or without ursolic acid. Ursolic acid at 10 and 30 {micro}g/ml
induced significantly (P < 0.05) 32 and 61 genes, respectively, and
19 genes were consistently induced. The consistently induced genes
have functions for chemotaxis and mobility (cheA, tap, tar, and motAB),
heat shock response (hslSTV and mopAB), and unknown functions (such
as b1566 and yrfHI). There were 31 and 17 genes repressed by 10 and
30 {micro}g of ursolic acid/ml, respectively, and 12 genes were consistently
repressed that have functions in cysteine synthesis (cysK) and sulfur
metabolism (cysD), as well as unknown functions (such as hdeAB and
yhaDFG). Ursolic acid inhibited biofilms without interfering with
quorum sensing, as shown with the V. harveyi AI-1 and AI-2 reporter
systems. As predicted by the differential gene expression, deleting
motAB counteracts ursolic acid inhibition (the paralyzed cells no
longer become too motile). Based on the differential gene expression,
it was also discovered that sulfur metabolism (through cysB) affects
biofilm formation (in the absence of ursolic acid).},
url = {http://aem.asm.org/cgi/content/abstract/71/7/4022}
}
@ARTICLE{Ren2010,
author = {Ren, Hongzu and Aleksunes, Lauren M. and Wood, Carmen and Vallanat,
Beena and George, Michael H. and Klaassen, Curtis D. and Corton,
J. Christopher},
title = {Characterization of Peroxisome Proliferator-Activated Receptor {alpha}--Independent
Effects of PPAR{alpha} Activators in the Rodent Liver: Di-(2-ethylhexyl)
phthalate also Activates the Constitutive-Activated Receptor},
journal = {Toxicol. Sci.},
year = {2010},
volume = {113},
pages = {45--59},
number = {1},
month = jan,
abstract = {Peroxisome proliferator chemicals (PPC) are thought to mediate their
effects in rodents on hepatocyte growth and liver cancer through
the nuclear receptor peroxisome proliferator-activated receptor (PPAR)
{alpha}. Recent studies indicate that the plasticizer di-(2-ethylhexyl)
phthalate (DEHP) increased the incidence of liver tumors in PPAR{alpha}-null
mice. We hypothesized that some PPC, including DEHP, induce transcriptional
changes independent of PPAR{alpha} but dependent on other nuclear
receptors, including the constitutive-activated receptor (CAR) that
mediates phenobarbital (PB) effects on hepatocyte growth and liver
tumor induction. To determine the potential role of CAR in mediating
effects of PPC, a meta-analysis was performed on transcript profiles
from published studies in which rats and mice were exposed to PPC
and compared the profiles to those produced by exposure to PB. Valproic
acid, clofibrate, and DEHP in rat liver and DEHP in mouse liver induced
genes, including Cyp2b family members that are known to be regulated
by CAR. Examination of transcript changes by Affymetrix ST 1.0 arrays
and reverse transcription-PCR in the livers of DEHP-treated wild-type,
PPAR{alpha}-null, and CAR-null mice demonstrated that (1) most ([~]94%)
of the transcriptional changes induced by DEHP were PPAR{alpha}-dependent,
(2) many PPAR{alpha}-independent genes overlapped with those regulated
by PB, (3) induction of genes Cyp2b10, Cyp3a11, and metallothionine-1
by DEHP was CAR dependent but PPAR{alpha}-independent, and (4) induction
of a number of genes (Cyp8b1, Gstm4, and Gstm7) was independent of
both CAR and PPAR{alpha}. Our results indicate that exposure to PPAR{alpha}
activators including DEHP leads to activation of multiple nuclear
receptors in the rodent liver.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/113/1/45}
}
@ARTICLE{RenaHesse2012,
author = {Rena Hesse, Amke and Hagemeier, Karin and Lürbke, Alexander and
Held, Jasmin and Friedman, Hana and Peterson, Alan and Brück, Wolfgang
and Kuhlmann, Tanja},
title = {XIAP protects oligodendrocytes against cell death in vitro but has
no functional role in toxic demyelination},
journal = {Glia},
year = {2012},
volume = {60},
pages = {271--280},
number = {2},
abstract = {Oligodendroglial damage and loss are typical characteristics of demyelinating
diseases such as multiple sclerosis (MS) and the leukodystrophies.
Axonal loss is the underlying cause of permanent neurological deficits
in MS and it is thought to arise from a combination of immune-mediated
axonal damage and the loss of trophic support to axons from myelin
sheaths after demyelination. Prevention of oligodendroglial damage
or death and demyelination are therefore attractive neuroprotective
treatment strategies. However, a better understanding of mechanisms
leading to oligodendroglial damage and demyelination is a prerequisite
for the development of such treatment options. Here, we demonstrate
that X-linked inhibitor of apoptosis (XIAP), the most potent member
of the inhibitor of apoptosis proteins (IAP) family is expressed
in oligodendrocytes in vivo and in vitro. Increased expression of
XIAP is associated with protection against selected cell death pathways,
whereas decreased expression increases oligodendroglial cell death
in vitro. However, lack of XIAP does not modulate oligodendroglial
cell death in toxic demyelination in vivo. © 2011 Wiley Periodicals,
Inc.},
doi = {10.1002/glia.21261},
issn = {1098-1136},
keywords = {oligodendrocytes, XIAP, cuprizone},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.21261}
}
@ARTICLE{Renard2007,
author = {Renard, Claire-Angelique and Labalette, Charlotte and Armengol, Carolina
and Cougot, Delphine and Wei, Yu and Cairo, Stefano and Pineau, Pascal
and Neuveut, Christine and de Reynies, Aurelien and Dejean, Anne
and Perret, Christine and Buendia, Marie-Annick},
title = {Tbx3 Is a Downstream Target of the Wnt/{beta}-Catenin Pathway and
a Critical Mediator of {beta}-Catenin Survival Functions in Liver
Cancer},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {901--910},
number = {3},
month = feb,
abstract = {Tbx3 encodes a transcriptional repressor that is important for diverse
patterning events during development, and Tbx3 mutation in humans
causes the ulnar-mammary syndrome. Here, we describe the identification
of Tbx3 in array-based search for genes downstream Wnt/{beta}-catenin
that are implicated in liver tumorigenesis. Overexpression of Tbx3
is closely associated with the mutational status of {beta}-catenin
in murine liver tumors induced by Myc as well as in human hepatocellular
carcinomas and hepatoblastomas. Moreover, Tbx3 transcription is activated
by ectopic expression of {beta}-catenin in mouse liver and in human
tumor cell lines. Evidence that Tbx3 transcription is directly regulated
by {beta}-catenin is provided by chromatin immunoprecipitation and
reporter assays. Although HepG2 cells stably transfected with Tbx3
display moderately enhanced growth rate, the dominant negative mutant
Tbx3-Y149S drastically inhibits hepatoma cell growth in vitro and
in vivo. Moreover, small interfering RNAs (siRNA) directed against
Tbx3 inhibit anchorage-independent growth of liver and colon carcinoma
cells. We further show that inhibition of Tbx3 expression by specific
siRNAs blocks {beta}-catenin-mediated cell survival and renders cells
sensitive to doxorubicin-induced apoptosis. Conversely, ectopic expression
of Tbx3 inhibits apoptosis induced by {beta}-catenin depletion. Marked
overexpression of Tbx3 in a subset of hepatoblastomas is associated
with chemotherapy-resistant phenotype and unfavorable patient outcome.
These results reveal an unsuspected role of Tbx3 as a mediator of
{beta}-catenin activities on cell proliferation and survival and
as an important player in liver tumorigenesis. [Cancer Res 2007;67(3):901-10]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/3/901}
}
@ARTICLE{Renella2011,
author = {Renella, Raffaele and Roberts, Nigel A. and Brown, Jill M. and De
Gobbi, Marco and Bird, Louise E. and Hassanali, Tasneem and Sharpe,
Jacqueline A. and Sloane-Stanley, Jacqueline and Ferguson, David
J. P. and Cordell, Jacqueline and Buckle, Veronica J. and Higgs,
Douglas R. and Wood, William G.},
title = {Codanin-1 mutations in congenital dyserythropoietic anemia type 1
affect HP1{alpha} localization in erythroblasts},
journal = {Blood},
year = {2011},
volume = {117},
pages = {6928-6938},
number = {25},
abstract = {Congenital dyserythropoietic anemia type 1 (CDA-1), a rare inborn
anemia characterized by abnormal chromatin ultrastructure in erythroblasts,
is caused by abnormalities in codanin-1, a highly conserved protein
of unknown function. We have produced 3 monoclonal antibodies to
codanin-1 that demonstrate its distribution in both nucleus and cytoplasm
by immunofluorescence and allow quantitative measurements of patient
and normal material by Western blot. A detailed analysis of chromatin
structure in CDA-1 erythroblasts shows no abnormalities in overall
histone composition, and the genome-wide epigenetic landscape of
several histone modifications is maintained. However, immunofluorescence
analysis of intermediate erythroblasts from patients with CDA-1 reveals
abnormal accumulation of HP1 in the Golgi apparatus. A link between
mutant codanin-1 and the aberrant localization of HP1 is supported
by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1
antibodies. Furthermore, we show colocalization of codanin-1 with
Sec23B, the protein defective in CDA-2 suggesting that the CDAs might
be linked at the molecular level. Mice containing a gene-trapped
Cdan1 locus demonstrate its widespread expression during development.
Cdan1gt/gt homozygotes die in utero before the onset of primitive
erythropoiesis, suggesting that Cdan1 has other critical roles during
embryogenesis.},
doi = {10.1182/blood-2010-09-308478},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/117/25/6928.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/25/6928}
}
@ARTICLE{Renkonen2009,
author = {Renkonen, J. and Mattila, P. and Lehti, S. and Mäkinen, J. and Sormunen,
R. and Tervo, T. and Paavonen, T. and Renkonen, R.},
title = {Birch pollen allergen Bet v 1 binds to and is transported through
conjunctival epithelium in allergic patients},
journal = {Allergy},
year = {2009},
volume = {64},
pages = {868--875},
number = {6},
abstract = {Background:  Previous work in type-I pollen allergies has mainly
focused on lymphocytes and immune responses. Here, we begin to analyse
with a systems biology view the differences in conjunctival epithelium
obtained from healthy and allergic subjects. Methods:  Transcriptomics
analysis combined with light and electron microscopic analysis of
birch pollen allergen Bet v 1 located within conjunctival epithelial
cells and tissues from birch allergic subjects and healthy controls
was carried out. Results:  Bet v 1 pollen allergen bound to conjunctival
epithelial cells within minutes after the exposure even during the
nonsymptomatic winter season only in allergic, but not in healthy
individuals. Light- and electron microscopy showed that Bet v 1 was
transported through the epithelium within lipid rafts/caveolae and
reached mast cells only in allergic patients, but not in healthy
individuals. Transcriptomics yielded 22 putative receptors expressed
at higher levels in allergic epithelium compared with healthy specimens.
A literature search indicated that out of these receptors, eight
(i.e. 37%) were associated with lipid rafts/caveolae, which suggested
again that Bet v 1 transport is lipid raft/caveola-dependent. Conclusions: 
We show a clear difference in the binding and uptake of Bet v 1 allergen
by conjunctival epithelial cells in allergic vs healthy subjects
and several putative lipid raft/caveolar receptors were identified,
which could mediate or be co-transported with this entry. The application
of discovery driven methodologies on human conjunctival epithelial
cells and tissues can provide new hypotheses worth a further analysis
to the molecular mechanisms of a complex multifactorial disease such
as type-I birch pollen allergy.},
issn = {1398-9995},
keywords = {allergy, caveola, epithelium, pollen, transport},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1398-9995.2008.01919.x}
}
@ARTICLE{Renkonen2010,
author = {Renkonen, J. and Mattila, P. and Parviainen, V. and Joenväärä,
S. and Toppila-Salmi, S. and Renkonen, R.},
title = {A network analysis of the single nucleotide polymorphisms in acute
allergic diseases},
journal = {Allergy},
year = {2010},
volume = {65},
pages = {40--47},
number = {1},
abstract = {Abstract Background:  Genetics of acute allergies has focused on
identifying single nucleotide polymorphisms (SNPs) within genes relevant
in the pathogenesis. In this study, we begin a systems biology analysis
of the interconnectivity and biological functions of these genes,
their transcripts and their corresponding proteins. Methods:  The
literature (Pubmed) was searched for SNPs within genes relevant in
acute allergic diseases. The SNP-modified genes were converted to
corresponding proteins and their protein–protein interactions were
searched from six different databases. This interaction network was
analysed with annotated vocabularies (ontologies), such as Gene Ontology,
Reactome and Nature pathway interaction database. Time-series transcriptomics
was performed with nasal epithelial cells obtained from allergic
patients and their healthy control subjects. Results:  A total
of 39 genes with SNPs related to acute allergic diseases were found
from a literature search. The corresponding proteins were then hooked
into a large protein–protein interaction network with the help
of various databases. Twenty-five SNP-related proteins had more than
one interacting protein and a network contained 95 proteins, and
182 connections could be generated. This network was 10-fold enriched
with protein kinases and proteins involved in the host–virus interaction
compared with background human proteome. Finally, eight of the 95
nodes on our network displayed nasal epithelial transcriptomal regulation
in a time-series analysis collected from birch allergic patients
during the spring pollen season. Conclusions:  Signal transduction
with special reference to host–virus interactions dominated in
the allergy-related protein interaction network. Systems level analysis
of allergy-related mutation can provide new insights into pathogenetic
mechanisms of the diseases.},
issn = {1398-9995},
keywords = {allergy, network, pathway pathogenesis, single nucleotide polymorphisms},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1398-9995.2009.02101.x}
}
@ARTICLE{Renn2008,
author = {Renn, Susan C. P. and Aubin-Horth, Nadia and Hofmann, Hans A.},
title = {Fish and chips: functional genomics of social plasticity in an African
cichlid fish},
journal = {J. Exp. Biol.},
year = {2008},
volume = {211},
pages = {3041--3056},
number = {18},
month = sep,
abstract = {Behavior and physiology are regulated by both environment and social
context. A central goal in the study of the social control of behavior
is to determine the underlying physiological, cellular and molecular
mechanisms in the brain. The African cichlid fish Astatotilapia burtoni
has long been used as a model system to study how social interactions
regulate neural and behavioral plasticity. In this species, males
are either socially dominant and reproductively active or subordinate
and reproductively suppressed. This phenotypic difference is reversible.
Using an integrative approach that combines quantitative behavioral
measurements, functional genomics and bioinformatic analyses, we
examine neural gene expression in dominant and subordinate males
as well as in brooding females. We confirm the role of numerous candidate
genes that are part of neuroendocrine pathways and show that specific
co-regulated gene sets (modules), as well as specific functional
gene ontology categories, are significantly associated with either
dominance or reproductive state. Finally, even though the dominant
and subordinate phenotypes are robustly defined, we find a surprisingly
high degree of individual variation in the transcript levels of the
very genes that are differentially regulated between these phenotypes.
The results of the present study demonstrate the molecular complexity
in the brain underlying social behavior, identify novel targets for
future studies, validate many candidate genes and exploit individual
variation in order to gain biological insights.},
url = {http://jeb.biologists.org/cgi/content/abstract/211/18/3041}
}
@ARTICLE{Rennel2007,
author = {Rennel, Emma and Mellberg, Sofie and Dimberg, Anna and Petersson,
Ludvig and Botling, Johan and Ameur, Adam and Westholm, Jakub Orzechowski
and Komorowski, Jan and Lassalle, Philippe and Cross, Michael J.
and Gerwins, Pär},
title = {Endocan is a VEGF-A and PI3K regulated gene with increased expression
in human renal cancer},
journal = {Experimental Cell Research},
year = {2007},
volume = {313},
pages = {1285--1294},
number = {7},
month = apr,
abstract = {An in vitro model of VEGF-A-induced angiogenesis was used to generate
transcription profiles of human microvascular endothelial cells.
Microarray analysis showed increased transcription of genes known
to regulate angiogenesis, but also genes that previously have not
been firmly associated with angiogenesis such as endocan, pinin,
plakophilin, phosphodiesterase 4B and gelsolin. Increased endocan
mRNA levels in response to VEGF-A in endothelial cells and in human
renal cancer have previously been reported. We now show increased
endocan protein levels in VEGF-A treated endothelial cells and in
human renal clear cell carcinoma. Increased protein expression was
observed both in tumor cells and in a subset of tumor vessels, while
expression in normal kidney tissue was low. VEGF-A seemed to be a
specific inducer of endocan transcription since FGF-2, PDGF-BB, HGF/SF
and EGF did not alter expression levels. Inhibition of PI3K with
LY294002 caused a 12-fold increase in endocan transcription suggesting
a repressive function of PI3K. In contrast inhibition of Src or MEK,
which are signaling pathways activated by VEGF-A, did not influence
basal or VEGF-A-induced endocan levels. In conclusion our study shows
that, among angiogenic growth factors, VEGF-A is a specific inducer
of endocan transcription which is translated into increased protein
levels in VEGF-A treated endothelial cells. Increased endocan protein
expression in human renal cancer suggests a role in tumor growth.},
issn = {0014-4827},
keywords = {Angiogenesis, Endocan, Microarray, Renal tumor, Vascular endothelial
growth factor, Endothelium},
url = {http://www.sciencedirect.com/science/article/B6WFC-4N0HJH9-1/2/e5ef729743bbb15730d4404186439a87}
}
@ARTICLE{Renneson2009,
author = {Renneson, Joelle and Dutta, Binita and Goriely, Stanislas and Danis,
Bénédicte and Lecomte, Sandra and Laes, Jean-François and Tabi,
Zsuzsanna and Goldman, Michel and Marchant, Arnaud},
title = {IL-12 and type I IFN response of neonatal myeloid DC to human CMV
infection},
journal = {Eur. J. Immunol.},
year = {2009},
volume = {39},
pages = {2789--2799},
number = {10},
abstract = {Abstract 10.1002/eji.200939414.abs Following congenital human CMV
(HCMV) infection, 15–20% of infected newborns develop severe health
problems whereas infection in immunocompetent adults rarely causes
illness. The immaturity of neonatal antigen presenting cells could
play a pivotal role in this susceptibility. Neonatal myeloid DC were
shown to be deficient in IFN-β and IL-12 synthesis in response to
TLR triggering. We studied the response of cord and adult blood-derived
myeloid DC to HCMV infection. Neonatal and adult DC were equally
susceptible to in vitro HCMV infection. Among immunomodulatory cytokines,
IL-12, IFN-β and IFN-λ1 were produced at lower levels by neonatal
as compared with adult DC. In contrast, neonatal and adult DC produced
similar levels of IFN-α and IFN-inducible genes. Microarray analysis
indicated that among the more than thousand genes up- or down-regulated
by HCMV infection of myeloid DC, 88 were differently regulated between
adult and neonatal DC. We conclude that neonatal and adult DC trigger
a partly different response to HCMV infection. The deficient IL-12
and mature IFN-α production by neonatal DC exposed to HCMV are likely
to influence the quality of the T lymphocyte response to HCMV infection
in early life.},
issn = {1521-4141},
keywords = {Cytokines, DC, IFN, Infectious diseases, Neonate immunity},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200939414}
}
@ARTICLE{Renninger2005,
author = {Renninger, Matthew L. and Seymour, Rosemarie and Lillard, James W.
and Sundberg, John P. and HogenEsch, Harm},
title = {Increased expression of chemokines in the skin of chronic proliferative
dermatitis mutant mice},
journal = {Experimental Dermatology},
year = {2005},
volume = {14},
pages = {906--913},
number = {12},
abstract = {Abstract:  Chemokines direct the migration of leukocytes to sites
of inflammation and are potential targets for anti-inflammatory therapy.
Chronic proliferative dermatitis (cpdm/cpdm) mutant mice develop
a persistent eosinophilic dermatitis associated with increased TH2
cytokines in the skin. Expression patterns of chemokines in the skin
of cpdm/cpdm mice were evaluated to define the mechanisms driving
cutaneous infiltration by leukocytes. RNA isolated from the skin
of mutant and littermate control mice revealed a significant increase
in Ccl1 (TCA-3), Ccl2 (MCP-1), Ccl11 (eotaxin), Ccl17 (TARC), Cxcl10
(IP-10), and the chemokine receptor Ccr3. The concentration of CCL11
protein was increased two- to threefold in the skin of cpdm/cpdm
mice by enzyme-linked immunosorbent assay. In vitro culture of primary
dermal fibroblasts from cpdm/cpdm and control mice with tumor necrosis
factor, IL-4, and IL-13 stimulation did not reveal differences in
their ability to secrete CCL11, suggesting that the increased chemokine
expression observed in the skin of cpdm/cpdm mice is most likely
caused by the increased TH2 cytokines in the dermis of this mouse
model. Treatment of cpdm/cpdm mice with CCL11-neutralizing polyclonal
antibodies did not affect the number of eosinophils in the skin or
the severity of the dermatitis. Neutralizing multiple chemokines
or chemokine receptors may be necessary to decrease eosinophil accumulation.
The cpdm/cpdm mutant mouse is a potentially useful model to determine
the role of various chemokines in eosinophil accumulation in chronic
inflammation.},
issn = {1600-0625},
keywords = {chemokines, dermatitis, eosinophils, mouse},
publisher = {Munksgaard International Publishers},
url = {http://dx.doi.org/10.1111/j.1600-0625.2005.00378.x}
}
@ARTICLE{Renthal2007,
author = {Renthal, William and Maze, Ian and Krishnan, Vaishnav and Covington
III, Herbert E. and Xiao, Guanghua and Kumar, Arvind and Russo, Scott
J. and Graham, Ami and Tsankova, Nadia and Kippin, Tod E. and Kerstetter,
Kerry A. and Neve, Rachael L. and Haggarty, Stephen J. and McKinsey,
Timothy A. and Bassel-Duby, Rhonda and Olson, Eric N. and Nestler,
Eric J.},
title = {Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations
to Chronic Emotional Stimuli},
journal = {Neuron},
year = {2007},
volume = {56},
pages = {517--529},
number = {3},
month = nov,
abstract = {Summary Previous work has identified alterations in histone acetylation
in animal models of drug addiction and depression. However, the mechanisms
which integrate drugs and stress with changes in chromatin structure
remain unclear. Here, we identify the activity-dependent class II
histone deacetylase, HDAC5, as a central integrator of these stimuli
with changes in chromatin structure and gene expression. Chronic,
but not acute, exposure to cocaine or stress decreases HDAC5 function
in the nucleus accumbens (NAc), a major brain reward region, which
allows for increased histone acetylation and transcription of HDAC5
target genes. This regulation is behaviorally important, as loss
of HDAC5 causes hypersensitive responses to chronic, not acute, cocaine
or stress. These findings suggest that proper balance of histone
acetylation is a crucial factor in the saliency of a given stimulus
and that disruption of this balance is involved in the transition
from an acute adaptive response to a chronic psychiatric illness.},
issn = {0896-6273},
keywords = {DNA, MOLNEURO, SYSNEURO},
url = {http://www.sciencedirect.com/science/article/B6WSS-4R2XTMN-C/2/9581393488f32fa970d6611335f79543}
}
@ARTICLE{Rentsch2006,
author = {Rentsch, Cyrill A. and Cecchini, Marco G. and Schwaninger, Ruth and
Germann, Markus and Markwalder, Regula and Heller, Manfred and van
der Pluijm, Gabri and Thalmann, George N. and Wetterwald, Antoinette},
title = {Differential expression of TGFβ-stimulated clone 22 in normal prostate
and prostate cancer},
journal = {Int. J. Cancer},
year = {2006},
volume = {118},
pages = {899--906},
number = {4},
abstract = {Abstract 10.1002/ijc.21449.abs The transforming growth factor-β (TGFβ)
superfamily and its downstream effector genes are key regulators
of epithelial homeostasis. Altered expression of these genes may
be associated with malignant transformation of the prostate gland.
The cDNA array analysis of differential expression of the TGFβ superfamily
and functionally related genes between patient-matched noncancerous
prostate (NP) and prostate cancer (PC) bulk tissue specimens highlighted
two genes, namely TGFβ-stimulated clone-22 (TSC-22) and Id4. Verification
of their mRNA expression by real-time PCR in patient-matched NP and
PC bulk tissue, in laser-captured pure epithelial and cancer cells
and in NP and PC cell lines confirmed TSC-22 underexpression, but
not Id4 overexpression, in PC and in human PC cell lines. Immunohistochemical
analysis showed that TSC-22 protein expression in NP is restricted
to the basal cells and colocalizes with the basal cell marker cytokeratin
5. In contrast, all matched PC samples lack TSC-22 immunoreactivity.
Likewise, PC cell lines do not show detectable TSC-22 protein expression
as shown by immunoblotting. TSC-22 should be considered as a novel
basal cell marker, potentially useful for studying lineage determination
within the epithelial compartment of the prostate. Conversely, lack
of TSC-22 seems to be a hallmark of malignant transformation of the
prostate epithelium. Accordingly, TSC-22 immunohistochemistry may
prove to be a diagnostic tool for discriminating benign lesions from
malignant ones of the prostate. The suggested tumour suppressor function
of TSC-22 warrants further investigation on its role in prostate
carcinogenesis and on the TSC-22 pathway as a candidate therapeutic
target in PC. © 2005 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {prostate cancer, TGFβ superfamily, TSC-22, basal cell marker},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.21449}
}
@ARTICLE{Rentsch2003,
author = {Rentsch, Cyrill A. and Schwaninger, Ruth and Wetterwald, Antoinette
and Markwalder, Regula and Klima, Irena and Geissbühler, Franziska
and Cecchini, Marco G. and Studer, Urs E. and Thalmann, George N.},
title = {The tumor suppresor gene TSC-22 (transforming growth factor-beta-stimulated
clone 22) mRNA-expression is downregulated in prostate cancer},
journal = {European Urology Supplements},
year = {2003},
volume = {2},
pages = {89--89},
number = {6},
issn = {1569-9056},
url = {http://www.sciencedirect.com/science/article/B6X11-4BHH1N2-2H/2/5be4819b8f5bfaa59a14ffe383ca44a1}
}
@ARTICLE{Rentsch2003a,
author = {Rentsch, Cyrill A. and Schwaninger, Ruth and Wetterwald, Antoinette
and Markwalder, Regula and Klima, Irena and Geissbühler, Franziska
and Pluijm, Gabri van der and Löwik, Clemens W. G. M. and Cecchini,
Marco G. and Studer, Urs E. and Thalmann, George N.},
title = {Bone morphogenetic protein-7 (BMP-7) is downregulated in prostate
cancer},
journal = {European Urology Supplements},
year = {2003},
volume = {2},
pages = {87--87},
number = {6},
issn = {1569-9056},
url = {http://www.sciencedirect.com/science/article/B6X11-4BHH1N2-2F/2/ea3b00371b9b16af200cfe4d0401523b}
}
@ARTICLE{Renzetti2009,
author = {Renzetti, S. and Arendt, E.K.},
title = {Effect of protease treatment on the baking quality of brown rice
bread: From textural and rheological properties to biochemistry and
microstructure},
journal = {Journal of Cereal Science},
year = {2009},
volume = {50},
pages = {22--28},
number = {1},
month = jul,
abstract = {In this study, protease treatment of brown rice (BR) batters was investigated
in order to evaluate its impact on the textural and baking properties
of BR bread. The enzymatic treatment improved bread quality by significantly
increasing specific volume (p < 0.05), while decreasing crumb hardness
and chewiness (p < 0.05). Fundamental rheology and viscometry of
batters revealed that protein hydrolysis induced lower complex modulus
and initial viscosity, while phase angle was unaffected. Flour pasting
properties were also affected, with a significant decrease in paste
viscosity and breakdown (p < 0.05). Protein analysis of batters revealed
that the enzymatic treatment induced the release of low molecular
weight proteins from macromolecular protein complexes. In conclusion,
a lower resistance to deformation of batters during proofing and
in the early stages of baking as well as the preserved batter elasticity
and the increased paste stability positively affected the breadmaking
performance.},
issn = {0733-5210},
keywords = {Brown rice bread, Microstructure, Rheology, Protease},
url = {http://www.sciencedirect.com/science/article/B6WHK-4W1BV6G-2/2/7e3722f34b82b7f56fbbc0011d15867d}
}
@ARTICLE{Renzetti2008,
author = {Renzetti, S. and Behr, J. and Vogel, R.F. and Arendt, E.K.},
title = {Transglutaminase polymerisation of buckwheat (Fagopyrum esculentum
Moench) proteins},
journal = {Journal of Cereal Science},
year = {2008},
volume = {48},
pages = {747--754},
number = {3},
month = nov,
abstract = {Recently, screening of transglutaminase (TGase) treatment on several
gluten-free cereals revealed significant improvements on the baking
performances of buckwheat flour by promoting protein networks. In
this study, the impact of TGase on the protein fractions of buckwheat
flour was investigated in order to better understand the activity
and specificity of the enzyme. Albumin, globulin, prolamin and glutelin
fractions were extracted from the flour and incubated with TGase.
Capillary electrophoresis, two dimensional (2D) gel electrophoresis
and size exclusion chromatography (SEC) were performed on each fraction.
Capillary electrophoresis and 2D gel electrophoresis revealed that
buckwheat main storage proteins, i.e. 2S albumin, 13S and 8S globulin,
were cross-linked after TGase treatment. SEC showed the presence
of high molecular weight (HMW) protein polymers in the TGase-treated
albumin and globulin fraction. Analysis of the amino acid composition
of the fractions revealed high amounts of glutamine and lysine residues
in all fractions. In conclusion, the increase in the average molecular
weight of buckwheat proteins and the formation of HMW protein polymers
after TGase treatment are responsible for the improved functionality
of buckwheat flour in terms of breadmaking potential. The enzyme
was revealed to be not fraction specific as all fractions were TGase-reactive.},
issn = {0733-5210},
keywords = {Buckwheat, Protein, Transglutaminase, Two dimensional gel electrophoresis},
url = {http://www.sciencedirect.com/science/article/B6WHK-4SH6B9N-1/2/245bc11f4d16e5ef7ea105d173d16253}
}
@ARTICLE{Renzetti2012,
author = {Stefano Renzetti and Juergen Behr and Rudi F. Vogel and Alberto Barbiroli
and Stefania Iametti and Francesco Bonomi and Elke K. Arendt},
title = {Transglutaminase treatment of brown rice flour: A chromatographic,
electrophoretic and spectroscopic study of protein modifications},
journal = {Food Chemistry},
year = {2012},
volume = {131},
pages = {1076 - 1085},
number = {4},
abstract = {Recently, it was shown that transglutaminase (TGase) treatment of
brown rice (BR) flour results in textural improvements of gluten-free
bread. In this study, changes in the protein profiles of BR flour
and protein fractions induced by TGase treatment were investigated
to better understand the activity and specificity of the enzyme.
Size-exclusion HPLC (SE-HPLC) profiles of flour extracts, under reducing
conditions, revealed the presence of macromolecular protein complexes,
as well as low molecular weight proteins. After TGase treatments
(10 U/g of proteins) a general reduction in peak intensities
indicated the polymerisation of BR proteins into larger, insoluble
complexes. Microchip capillary electrophoresis and two-dimensional
(2D) gel electrophoresis revealed that the α and β glutelin subunits
were primary substrates for the polymerisation reaction, whereas
albumins and globulins were only slightly affected. SE-HPLC of the
protein fractions revealed glutelins’ polymerisation into high
molecular weight structures after TGase treatment. Dynamic light
scattering measurements showed that new supramolecular aggregates
of glutelins co-existed with the macromolecular complexes already
present in the untreated fraction. Front-face fluorescence approaches
indicated that TGase treatment caused a decrease in protein surface
hydrophobicity of BR flour, but not of the glutelin suspensions.
It is concluded that the large protein complexes resulting from glutelin
polymerisation and the stronger hydrophobic interactions among proteins
result in the improved textural properties of TGase-treated BR bread.},
doi = {10.1016/j.foodchem.2011.08.029},
issn = {0308-8146},
keywords = {ANS1,8 anilinonaphthalene sulfonate, sodium salt},
url = {http://www.sciencedirect.com/science/article/pii/S0308814611011617}
}
@ARTICLE{Renzetti2010,
author = {Renzetti, S. and Courtin, C.M. and Delcour, J.A. and Arendt, E.K.},
title = {Oxidative and proteolytic enzyme preparations as promising improvers
for oat bread formulations: Rheological, biochemical and microstructural
background},
journal = {Food Chemistry},
year = {2010},
volume = {119},
pages = {1465--1473},
number = {4},
month = apr,
abstract = {Commercial preparations of laccase (LAC) and glucose oxidase (GO)
(0.01% and 0.1% addition levels), as well as of a protease (PR) (0.001%
and 0.01% addition levels) were tested for their impact on the breadmaking
performance of gluten-free oat flour. LAC 0.1%, PR 0.001% and PR
0.01% additions significantly improved oat bread quality, as they
increased specific volume and decreased crumb hardness and chewiness.
In contrast, GO 0.1% addition revealed detrimental effects, as it
resulted in the hardest bread crumb. The improved breadmaking performances
of oat breads with LAC and PR addition was explained by the increase
in batter softness, deformability and elasticity which were achieved
upon addition of these enzyme preparations, both containing discernible
levels of endo-[beta]-glucanase side activity. With LAC, the effect
is due to prevalence of [beta]-glucan depolymerisation over protein
polymerisation while, with PR, it is due to the combined effect of
protein and [beta]-glucan degradation. Extensive protein hydrolysis
during baking may have increased functionality of the soluble protein
fraction. In contrast, extensive protein polymerisation was detrimental,
as indicated by GO addition.},
issn = {0308-8146},
keywords = {Oat bread, Microstructure, Rheology, Laccase, Glucose oxidase, Protease,
[beta]-Glucan},
url = {http://www.sciencedirect.com/science/article/B6T6R-4X6MT1R-H/2/84450c1e7a3b661e2a7777bfe8cce4d9}
}
@ARTICLE{Renzoni2006,
author = {Renzoni, Adriana and Barras, Christine and Francois, Patrice and
Charbonnier, Yvan and Huggler, Elzbieta and Garzoni, Christian and
Kelley, William L. and Majcherczyk, Paul and Schrenzel, Jacques and
Lew, Daniel P. and Vaudaux, Pierre},
title = {Transcriptomic and Functional Analysis of an Autolysis-Deficient,
Teicoplanin-Resistant Derivative of Methicillin-Resistant Staphylococcus
aureus},
journal = {Antimicrob. Agents Chemother.},
year = {2006},
volume = {50},
pages = {3048--3061},
number = {9},
month = sep,
abstract = {The molecular basis of glycopeptide-intermediate S. aureus (GISA)
isolates is not well defined though frequently involves phenotypes
such as thickened cell walls and decreased autolysis. We have exploited
an isogenic pair of teicoplanin-susceptible (strain MRGR3) and teicoplanin-resistant
(strain 14-4) methicillin-resistant S. aureus strains for detailed
transcriptomic profiling and analysis of altered autolytic properties.
Strain 14-4 displayed markedly deficient Triton X-100-triggered autolysis
compared to its teicoplanin-susceptible parent, although microarray
analysis paradoxically did not reveal significant reductions in expression
levels of major autolytic genes atl, lytM, and lytN, except for sle1,
which showed a slight decrease. The most important paradox was a
more-than-twofold increase in expression of the cidABC operon in
14-4 compared to MRGR3, which was correlated with decreased expression
of autolysis negative regulators lytSR and lrgAB. In contrast, the
autolysis-deficient phenotype of 14-4 was correlated with both increased
expression of negative autolysis regulators (arlRS, mgrA, and sarA)
and decreased expression of positive regulators (agr RNAII and RNAIII).
Quantitative bacteriolytic assays and zymographic analysis of concentrated
culture supernatants showed a striking reduction in Atl-derived,
extracellular bacteriolytic hydrolase activities in 14-4 compared
to MRGR3. This observed difference was independent of the source
of cell wall substrate (MRGR3 or 14-4) used for analysis. Collectively,
our results suggest that altered autolytic properties in 14-4 are
apparently not driven by significant changes in the transcription
of key autolytic effectors. Instead, our analysis points to alternate
regulatory mechanisms that impact autolysis effectors which may include
changes in posttranscriptional processing or export.},
url = {http://aac.asm.org/cgi/content/abstract/50/9/3048}
}
@ARTICLE{Renzoni2004,
author = {Renzoni, Adriana and Francois, Patrice and Li, Dongmei and Kelley,
William L. and Lew, Daniel P. and Vaudaux, Pierre and Schrenzel,
Jacques},
title = {Modulation of Fibronectin Adhesins and Other Virulence Factors in
a Teicoplanin-Resistant Derivative of Methicillin-Resistant Staphylococcus
aureus},
journal = {Antimicrob. Agents Chemother.},
year = {2004},
volume = {48},
pages = {2958--2965},
number = {8},
month = aug,
abstract = {The impact of glycopeptide resistance on the molecular regulation
of Staphylococcus aureus virulence and attachment to host tissues
is poorly documented. We compared stable teicoplanin-resistant methicillin-resistant
S. aureus (MRSA) strain 14-4 with its teicoplanin-susceptible MRSA
parent, strain MRGR3, which exhibits a high degree of virulence in
a rat model of chronic foreign body MRSA infection. The levels of
fibronectin-mediated adhesion and surface display of fibronectin-binding
proteins were higher in teicoplanin-resistant strain 14-4 than in
its teicoplanin-susceptible parent or a teicoplanin-susceptible revertant
(strain 14-4rev) that spontaneously emerged during tissue cage infection.
Quantitative reverse transcription-PCR (qRT-PCR) showed four- and
twofold higher steady-state levels of fnbA and fnbB transcripts,
respectively, in strain 14-4 than in its teicoplanin-susceptible
counterparts. Analysis of global regulatory activities by qRT-PCR
revealed a strong reduction in the steady-state levels of RNAIII
and RNAII in the teicoplanin-resistant strain compared to in its
teicoplanin-susceptible counterparts. In contrast, sarA mRNA levels
were more than fivefold higher in strain 14-4 than in MRGR3 and 14-4rev.
Furthermore, the alternative transcription factor sigma B had a higher
level of functional activity in the teicoplanin-resistant strain
than in its teicoplanin-susceptible counterparts, as evidenced by
significant increases in both the sigma B-dependent asp23 mRNA levels
and the sarA P3 promoter-derived transcript levels, as assayed by
qRT-PCR and Northern blotting, respectively. These data provide further
evidence that the emergence of glycopeptide resistance is linked
by still poorly understood molecular pathways with significant pleiotropic
changes in the expression and regulation of some major virulence
genes. These molecular and phenotypic changes may have a profound
impact on the bacterial adhesion and colonization properties of such
multiresistant organisms.},
url = {http://aac.asm.org/cgi/content/abstract/48/8/2958}
}
@ARTICLE{Repass2009,
author = {Repass, John F. and Laurent, Micheline N. and Carter, Carla and Reizis,
Boris and Bedford, Mark T. and Cardenas, Kim and Narang, Priyanka
and Coles, Mark and Richie, Ellen R.},
title = {IL7-hCD25 and IL7-Cre BAC transgenic mouse lines: New tools for analysis
of IL-7 expressing cells},
journal = {Genesis},
year = {2009},
volume = {47},
pages = {281--287},
number = {4},
abstract = {Abstract 10.1002/dvg.20497.abs IL-7 is a cytokine that is required
for T-cell development and homeostasis as well as for lymph node
organogenesis. Despite the importance of IL-7 in the immune system
and its potential therapeutic relevance, questions remain regarding
the sites of IL-7 synthesis, specific cell types involved and molecular
mechanisms regulating IL-7 expression. To address these issues, we
generated two bacterial artificial chromosome (BAC) transgenic mouse
lines in which IL-7 regulatory elements drive expression of either
Cre recombinase or a human CD25 (hCD25) cell surface reporter molecule.
Expression of the IL-7.hCD25 BAC transgene, detected by reactivity
with anti-hCD25 antibody, mimicked endogenous IL-7 expression. Fetal
and adult tissues from crosses between IL-7.Cre transgenic mice and
Rosa26R or R26-EYFP reporters demonstrated X-gal or YFP staining
in tissues known to express endogenous IL-7 at some stage during
development. These transgenic lines provide novel genetic tools to
identify IL-7 producing cells in various tissues and to manipulate
gene expression selectively in IL-7 expressing cells. genesis 47:281–287,
2009. © 2009 Wiley-Liss, Inc.},
issn = {1526-968X},
keywords = {IL-7, BAC transgene, Cre recombinase},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/dvg.20497}
}
@ARTICLE{Replogle2008,
author = {Replogle, Kirstin and Arnold, Arthur and Ball, Gregory and Band,
Mark and Bensch, Staffan and Brenowitz, Eliot and Dong, Shu and Drnevich,
Jenny and Ferris, Margaret and George, Julia and Gong, George and
Hasselquist, Dennis and Hernandez, Alvaro and Kim, Ryan and Lewin,
Harris and Liu, Lei and Lovell, Peter and Mello, Claudio and Naurin,
Sara and Rodriguez-Zas, Sandra and Thimmapuram, Jyothi and Wade,
Juli and Clayton, David},
title = {The Songbird Neurogenomics (SoNG) Initiative: Community-based tools
and strategies for study of brain gene function and evolution},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {131},
number = {1},
abstract = {BACKGROUND:Songbirds hold great promise for biomedical, environmental
and evolutionary research. A complete draft sequence of the zebra
finch genome is imminent, yet a need remains for application of genomic
resources within a research community traditionally focused on ethology
and neurobiological methods. In response, we developed a core set
of genomic tools and a novel collaborative strategy to probe gene
expression in diverse songbird species and natural contexts.RESULTS:We
end-sequenced cDNAs from zebra finch brain and incorporated additional
sequences from community sources into a database of 86,784 high quality
reads. These assembled into 31,658 non-redundant contigs and singletons,
which we annotated via BLAST search of chicken and human databases.
The results are publicly available in the ESTIMA:Songbird database.
We produced a spotted cDNA microarray with 20,160 addresses representing
17,214 non-redundant products of an estimated 11,500–15,000 genes,
validating it by analysis of immediate-early gene (zenk) gene activation
following song exposure and by demonstrating effective cross hybridization
to genomic DNAs of other songbird species in the Passerida Parvorder.
Our assembly was also used in the design of the "Lund-zfa" Affymetrix
array representing ~22,000 non-redundant sequences. When the two
arrays were hybridized to cDNAs from the same set of male and female
zebra finch brain samples, both arrays detected a common set of regulated
transcripts with a Pearson correlation coefficient of 0.895. To stimulate
use of these resources by the songbird research community and to
maintain consistent technical standards, we devised a "Community
Collaboration" mechanism whereby individual birdsong researchers
develop experiments and provide tissues, but a single individual
in the community is responsible for all RNA extractions, labelling
and microarray hybridizations.CONCLUSION:Immediately, these results
set the foundation for a coordinated set of 25 planned experiments
by 16 research groups probing fundamental links between genome, brain,
evolution and behavior in songbirds. Energetic application of genomic
resources to research using songbirds should help illuminate how
complex neural and behavioral traits emerge and evolve.},
doi = {10.1186/1471-2164-9-131},
issn = {1471-2164},
pubmedid = {18366674},
url = {http://www.biomedcentral.com/1471-2164/9/131}
}
@ARTICLE{Repunte-Canonigo2010,
author = {Repunte-Canonigo, Vez and van der Stap, Lena D. and Chen, Jihuan
and Sabino, Valentina and Wagner, Ulrich and Zorrilla, Eric P. and
Schumann, Gunter and Roberts, Amanda J. and Sanna, Pietro Paolo},
title = {Genome-wide gene expression analysis identifies K-ras as a regulator
of alcohol intake},
journal = {Brain Research},
year = {2010},
volume = {1339},
pages = {1--10},
month = jun,
abstract = {Adaptations in the anterior cingulate cortex (ACC) have been implicated
in alcohol and drug addiction. To identify genes that may contribute
to excessive drinking, here we performed microarray analyses in laser
microdissected rat ACC after a single or repeated administration
of an intoxicating dose of alcohol (3 g/kg). Expression of the small
G protein K-ras was differentially regulated following both single
and repeated alcohol administration. We also observed that voluntary
alcohol intake in K-ras heterozygous null mice (K-ras+/-) did not
increase after withdrawal from repeated cycles of intermittent ethanol
vapor exposure, unlike in their wild-type littermates. To identify
K-ras regulated pathways, we then profiled gene expression in the
ACC of K-ras+/-, heterozygous null mice for the K-ras negative regulator
Nf1 (Nf1+/-) and wild-type mice following repeated administration
of an intoxicating dose of alcohol. Pathway analysis showed that
alcohol differentially affected various pathways in a K-ras dependent
manner - some of which previously shown to be regulated by alcohol
- including the insulin/PI3K pathway, the NF-[kappa]B, the phosphodiesterases
(PDEs) pathway, the Jak/Stat and the adipokine signaling pathways.
Altogether, the data implicate K-ras-regulated pathways in the regulation
of excessive alcohol drinking after a history of dependence.},
issn = {0006-8993},
keywords = {Neural plasticity, Jak/Stat, PI3K, ERK, MAPK, Adipokine, GSEA},
url = {http://www.sciencedirect.com/science/article/B6SYR-4YTN426-1/2/e1364baf3ce41c614ac16979f3fa1637}
}
@ARTICLE{Rescan2007,
author = {Rescan, Pierre-Yves and Montfort, Jerome and Rallière, Cécile and
Le Cam, Aurélie and Esquerré, Diane and Hugot, Karine},
title = {Dynamic gene expression in fish muscle during recovery growth induced
by a fasting-refeeding schedule},
journal = {BMC Genomics},
year = {2007},
volume = {8},
pages = {438},
number = {1},
abstract = {BACKGROUND:Recovery growth is a phase of rapid growth that is triggered
by adequate refeeding of animals following a period of weight loss
caused by starvation. In this study, to obtain more information on
the system-wide integration of recovery growth in muscle, we undertook
a time-course analysis of transcript expression in trout subjected
to a food deprivation-refeeding sequence. For this purpose complex
targets produced from muscle of trout fasted for one month and from
muscle of trout fasted for one month and then refed for 4, 7, 11
and 36 days were hybridized to cDNA microarrays containing 9023 clones.RESULTS:Significance
analysis of microarrays (SAM) and temporal expression profiling led
to the segregation of differentially expressed genes into four major
clusters. One cluster comprising 1020 genes with high expression
in muscle from fasted animals included a large set of genes involved
in protein catabolism. A second cluster that included approximately
550 genes with transient induction 4 to 11 days post-refeeding was
dominated by genes involved in transcription, ribosomal biogenesis,
translation, chaperone activity, mitochondrial production of ATP
and cell division. A third cluster that contained 480 genes that
were up-regulated 7 to 36 days post-refeeding was enriched with genes
involved in reticulum and Golgi dynamics and with genes indicative
of myofiber and muscle remodelling such as genes encoding sarcomeric
proteins and matrix compounds. Finally, a fourth cluster of 200 genes
overexpressed only in 36-day refed trout muscle contained genes with
function in carbohydrate metabolism and lipid biosynthesis. Remarkably,
among the genes induced were several transcriptional regulators which
might be important for the gene-specific transcriptional adaptations
that underlie muscle recovery.CONCLUSION:Our study is the first demonstration
of a coordinated expression of functionally related genes during
muscle recovery growth. Furthermore, the generation of a useful database
of novel genes associated with muscle recovery growth will allow
further investigations on particular genes, pathways or cellular
process involved in muscle growth and regeneration.},
doi = {10.1186/1471-2164-8-438},
issn = {1471-2164},
owner = {Meike Kuschel},
pubmedid = {18045468},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2164/8/438}
}
@ARTICLE{Resnick2006,
author = {Resnick, M B and Sabo, E and Meitner, P A and Kim, S S and Cho, Y
and Kim, H K and Tavares, R and Moss, S F},
title = {Global analysis of the human gastric epithelial transcriptome altered
by Helicobacter pylori eradication in vivo},
journal = {Gut},
year = {2006},
volume = {55},
pages = {1717--1724},
number = {12},
month = dec,
abstract = {Objective: The transcriptional profile of gastric epithelial cell
lines cocultured with Helicobacter pylori and the global gene expression
of whole gastric mucosa has been described previously. We aimed to
overcome limitations of previous studies by determining the effects
of H pylori eradication on the transcriptome of purified human gastric
epithelium using each patient as their own control. Design: Laser
capture microdissection (LCM) was used to extract mRNA from paraffin-embedded
antral epithelium from 10 patients with peptic ulcer disease, before
and after H pylori eradication. mRNA was reverse transcribed and
applied on to Affymetrix cDNA microarray chips customised for formalin-fixed
tissue. Differentially expressed genes were identified and a subset
validated by real-time polymerase chain reaction (PCR). Results:
A total of 13 817 transcripts decreased and 9680 increased after
H pylori eradication. Applying cut-off criteria (p<0.02, fold-change
threshold 2.5) reduced the sample to 98 differentially expressed
genes. Genes detected included those previously implicated in H pylori
pathophysiology such as interleukin 8, chemokine ligand 3, {beta}
defensin and somatostatin, as well as novel genes such as GDDR (TFIZ1),
chemokine receptors 7 and 8, and gastrokine. Conclusions: LCM of
archival specimens has enabled the identification of gastric epithelial
genes whose expression is considerably altered after H pylori eradication.
This study has confirmed the presence of genes previously implicated
in the pathogenesis of H pylori, as well as highlighted novel candidates
for further investigation.},
url = {http://gut.bmj.com/cgi/content/abstract/55/12/1717}
}
@ARTICLE{Resuehr2006,
author = {Resuehr, D. and Sikes, H. E. and Olcese, J.},
title = {Exploratory Investigation of the Effect of Melatonin and Caloric
Restriction on the Temporal Expression of Murine Hypothalamic Transcripts},
journal = {Journal of Neuroendocrinology},
year = {2006},
volume = {18},
pages = {279--289},
number = {4},
abstract = {Abstract Circadian rhythms of behaviour and gene expression are coupled
to endogenous neuronal oscillators located in the hypothalamic suprachiasmatic
nuclei (SCN), which are synchronised by the environmental light cycle.
Besides light, other factors such as the pineal hormone melatonin,
temperature and feeding have entraining properties. During senescence,
the circadian system becomes weaker and susceptible to desynchronisation.
It is unknown to what extent age-related changes are the result of
the deterioration of the hypothalamic master clock. Supplementing
ageing mice with melatonin as well as maintaining them on a hypocaloric
diet extends the life span and delays age-related diseases. By means
of DNA microarrays and the quantitative polymerase chain reaction,
we have conducted an exploratory study to compare the effect of long-term
melatonin substitution (MEL) and caloric restriction (CR) on circadian
gene expression in hypothalamic samples, which contained the SCN
as well as other important nuclei involved in nutrient balance, reproduction,
and so on. Over 4% of the hypothalamic transcripts showed an overt
circadian rhythm in expression, and many of these contain E boxes
in their promoter regions, suggesting a direct regulation by circadian
clock genes. MEL and CR significantly influenced some of these rhythmically
expressed transcripts, but often in opposite ways. Importantly, our
studies emphasise that the apparent direction of treatment effects
(i.e. up-regulation versus down-regulation) depends on the time of
day at which the samples are compared.},
issn = {1365-2826},
keywords = {melatonin, caloric restriction, circadian, hypothalamus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2826.2006.01414.x}
}
@ARTICLE{Reumann2010,
author = {Reumann, Marie K. and Nair, Turya and Strachna, Olga and Boskey,
Adele L. and Mayer-Kuckuk, Philipp},
title = {Production of VEGF receptor 1 and 2 mRNA and protein during endochondral
bone repair is differential and healing phase specific},
journal = {J Appl Physiol},
year = {2010},
volume = {109},
pages = {1930--1938},
number = {6},
month = dec,
abstract = {Physiological disturbances, including temporary hypoxia, are expected
to drive angiogenesis during bone repair. Evidence suggests that
the angiogenic ligand vascular endothelial growth factor (VEGF)-A
plays an important role in this process. We characterized the expression
of two receptors that are essential for mediating VEGF signaling,
VEGFR1/Flt-1 and VEGFR2/Flk-1/KDR, in a mouse rib fracture model.
Their mRNA and protein levels were assessed in four healing phases,
which were characterized histologically as hemorrhage formation on
postfracture day (PFD) 1, inflammatory response on PFD 3, initiation
of callus development on PFD 7, and the presence of a mature callus
on PFD 14. Transcript was detected for VEGFR1 and VEGFR2, as well
as VEGF. While mRNA expression of VEGFR1 was monophasic throughout
all healing phases, VEGFR2 showed a biphasic profile with significantly
increased mRNA expression during callus formation and maturation.
Expression of VEGF mRNA was characterized by a more gradual increase
during callus formation. The protein level for VEGFR1 was below detection
sensitivity during the initial healing phase. It was then restored
to a stable level, detectable through the subsequent healing phases.
Hence, the VEGFR1 protein levels partially mirrored the transcript
expression profile. In comparison, the protein level of VEGFR2 increased
gradually during the healing phases and peaked at callus maturation.
This correlated well with the transcriptional expression of VEGFR2.
Intact bone from age-matched male mice had considerable protein levels
of VEGFR1 and VEGF, but no detectable VEGFR2. Together, these findings
uncovered expression signatures of the VEGF-VEGFR axis in endochondral
bone repair.},
comment = {10.1152/japplphysiol.00839.2010},
url = {http://jap.physiology.org/cgi/content/abstract/109/6/1930}
}
@ARTICLE{Reuwer2011,
author = {Reuwer, Anne Q and van Eijk, Marco and Houttuijn-Bloemendaal, Felicia
M and van der Loos, Chris M and Claessen, Nike and Teeling, Peter
and Kastelein, John J P and Hamann, Jorg and Goffin, Vincent and
von der Thusen, Jan H and Twickler, Marcel Th B and Aten, Jan},
title = {The prolactin receptor is expressed in macrophages within human carotid
atherosclerotic plaques: a role for prolactin in atherogenesis?},
journal = {J. Endocrinol.},
year = {2011},
volume = {208},
pages = {107--117},
number = {2},
month = feb,
abstract = {Atherosclerotic vascular disease is the consequence of a chronic inflammatory
process, and prolactin has been shown to be a component of the inflammatory
response. Additionally, recent studies indicate that prolactin contributes
to an atherogenic phenotype. We hypothesized that this may be the
result of a direct effect of prolactin on atherogenesis through activation
of the prolactin receptor. Human carotid atherosclerotic plaques
were obtained from patients by endarteriectomies. The mRNA of prolactin
receptor, but not of prolactin, was detected in these atherosclerotic
plaques by quantitative real-time PCR. In situ hybridization confirmed
the expression of the prolactin receptor in mononuclear cells. Analysis
at the protein level using immunohistochemistry and immunoelectron
microscopy revealed that the prolactin receptor was abundantly present
in macrophages near the lipid core and shoulder regions of the plaques.
Our findings demonstrate that the prolactin receptor is present in
macrophages of the atherosclerotic plaque at sites of most prominent
inflammation. We therefore propose that prolactin receptor signaling
contributes to the local inflammatory response within the atherosclerotic
plaque and thus to atherogenesis.},
comment = {10.1677/JOE-10-0076},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/208/2/107}
}
@ARTICLE{Revaud2011,
author = {Revaud, D and Caradec, J and Sirab, N and Delacotte, N and Loric,
S},
title = {Reply: Choosing a stable housekeeping gene and protein is essential
in generating valid gene and protein expression results},
journal = {Br J Cancer},
year = {2011},
volume = {104},
pages = {1056--1056},
number = {6},
month = mar,
issn = {0007-0920},
publisher = {Cancer Research UK},
url = {http://dx.doi.org/10.1038/bjc.2011.36}
}
@ARTICLE{Revet2008,
author = {Revet, Ingrid and Huizenga, Gerda and Chan, Alvin and Koster, Jan
and Volckmann, Richard and van Sluis, Peter and Øra, Ingrid and Versteeg,
Rogier and Geerts, Dirk},
title = {The MSX1 homeobox transcription factor is a downstream target of
PHOX2B and activates the Delta-Notch pathway in neuroblastoma},
journal = {Experimental Cell Research},
year = {2008},
volume = {314},
pages = {707--719},
number = {4},
month = feb,
abstract = {Neuroblastoma is an embryonal tumour of the peripheral sympathetic
nervous system (SNS). One of the master regulator genes for peripheral
SNS differentiation, the homeobox transcription factor PHOX2B, is
mutated in familiar and sporadic neuroblastomas. Here we report that
inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8
down-regulates MSX1, a homeobox gene important for embryonic neural
crest development. Inducible expression of MSX1 in SJNB-8 caused
inhibition of both cell proliferation and colony formation in soft
agar. Affymetrix micro-array and Northern blot analysis demonstrated
that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1,
NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated.
Western blot analysis showed that MSX1 induction caused cleavage
of the NOTCH3 protein to its activated form, further confirming activation
of the Delta-Notch pathway. These experiments describe for the first
time regulation of the Delta-Notch pathway by MSX1, and connect these
genes to the PHOX2B oncogene, indicative of a role in neuroblastoma
biology. Affymetrix micro-array analysis of a neuroblastic tumour
series consisting of neuroblastomas and the more benign ganglioneuromas
showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas.
This suggests a block in differentiation of these tumours at distinct
developmental stages or lineages.},
issn = {0014-4827},
keywords = {Delta, Affymetrix, MSX1, Neuroblastoma, Notch, PHOX2B, Ganglioneuroma},
url = {http://www.sciencedirect.com/science/article/B6WFC-4RC6RB7-1/2/cbdfeec7c4fb23b43d42352da0331822}
}
@ARTICLE{Revillion2006,
author = {Revillion, Francoise and Charlier, Madia and Lhotellier, Valerie
and Hornez, Louis and Giard, Sylvia and Baranzelli, Marie-Christine
and Djiane, Jean and Peyrat, Jean-Philippe},
title = {Messenger RNA Expression of Leptin and Leptin Receptors and their
Prognostic Value in 322 Human Primary Breast Cancers},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {2088--2094},
number = {7},
month = apr,
abstract = {Purpose: Leptin and obesity are clearly related, and obesity is associated
with an increased risk of breast cancer. We therefore measured the
expression of leptin and its two main receptor isoforms, OBR-L and
OBR-S, in 322 breast cancers. We analyzed their relations with the
classical prognostic factors and with survival to establish their
links with breast cancer. Experimental Design: The expression of
leptin and its receptors was quantified by real-time reverse transcription-PCR,
using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence detector
system (Applied Biosystems, Courtaboeuf, France). TATA box binding
protein was used to normalize expression. The human breast cancer
cell, SK-BR-3, expressing the three targets, was chosen as the calibrator
sample (i.e., target expression = 1). Results: All the tumors expressed
both receptors, and 318 of 322 expressed leptin. These three variables
correlated positively with each other and with estradiol and progesterone
receptors, whereas they correlated negatively with histoprognostic
grading and tumor diameter. OBR-L/OBR-S expression was inversely
correlated with progesterone receptors. Patients with elevated OBR-S
expression had longer relapse-free survival (P = 0.008), whereas
high OBR-L/OBR-S was associated with a shorter relapse-free survival
(P = 0.05). In Cox multivariate analyses, OBR-S maintained its prognostic
value (P = 0.02; relative risk, 0.51). Conclusions: This study shows
that (a) almost all of the breast cancers coexpress leptin and its
two main isoforms of receptors, suggesting that the human epithelial
breast cancer cells respond to leptin acting via an autocrine pathway;
(b) high expression levels of leptin and leptin receptors are biological
markers of a more differentiated phenotype; and that (c) OBR-S is
an independent prognostic factor.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/7/2088}
}
@ARTICLE{Revillion2008,
author = {Revillion, F. and Lhotellier, V. and Hornez, L. and Bonneterre, J.
and Peyrat, J.-P.},
title = {ErbB/HER ligands in human breast cancer, and relationships with their
receptors, the bio-pathological features and prognosis},
journal = {Ann. Onc.},
year = {2008},
volume = {19},
pages = {73--80},
number = {1},
month = jan,
abstract = {Background: The aim of this study is to provide an expression profile
of ErbB/HER ligands in breast cancer. We analysed the relationships
with their receptors, the bio-pathological features and prognosis.
Patients and methods: Epidermal growth factor (EGF), transforming
growth factor-{alpha} (TGF{alpha}), amphiregulin (AREG), betacellulin
(BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin
(EREG) and neuregulins1-4 (NRG1-4) were quantified in 363 tumours
by real-time reverse transcription-polymerase chain reaction using
TaqMan probes. Results: Ligands were detected in 80%-96% of the cases,
except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed
in 304 cases (cut-off: upper quartile). Almost all combinations of
receptor and ligand co-expressions were observed, but TGF{alpha}
is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3
in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing
HER2/HER4. EGF and AREG were associated with estradiol receptors,
small tumour size, low histoprognostic grading, high HER4 levels.
TGF{alpha}, HB-EGF and NRG2 were negatively related to these parameters.
In Cox univariate analyses, EGF was a prognostic factor. Conclusion:
Our study demonstrates that (i) ErbB/HER ligands, including BTC and
EREG, are expressed in most breast cancers; and (ii) TGF{alpha},
HB-EGF and NRG2 high expressions are related to the biological aggressiveness
of the tumours.},
url = {http://annonc.oxfordjournals.org/cgi/content/abstract/19/1/73}
}
@ARTICLE{Reyal2005,
author = {Reyal, Fabien and Stransky, Nicolas and Bernard-Pierrot, Isabelle
and Vincent-Salomon, Anne and de Rycke, Yann and Elvin, Paul and
Cassidy, Andrew and Graham, Alexander and Spraggon, Carolyn and Desille,
Yoann and Fourquet, Alain and Nos, Claude and Pouillart, Pierre and
Magdelenat, Henri and Stoppa-Lyonnet, Dominique and Couturier, Jerome
and Sigal-Zafrani, Brigitte and Asselain, Bernard and Sastre-Garau,
Xavier and Delattre, Olivier and Thiery, Jean Paul and Radvanyi,
Francois},
title = {Visualizing Chromosomes as Transcriptome Correlation Maps: Evidence
of Chromosomal Domains Containing Co-expressed Genes--A Study of
130 Invasive Ductal Breast Carcinomas},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {1376--1383},
number = {4},
month = feb,
abstract = {Completion of the working draft of the human genome has made it possible
to analyze the expression of genes according to their position on
the chromosomes. Here, we used a transcriptome data analysis approach
involving for each gene the calculation of the correlation between
its expression profile and those of its neighbors. We used the U133
Affymetrix transcriptome data set for a series of 130 invasive ductal
breast carcinomas to construct chromosomal maps of gene expression
correlation (transcriptome correlation map). This highlighted nonrandom
clusters of genes along the genome with correlated expression in
tumors. Some of the gene clusters identified by this method probably
arose because of genetic alterations, as most of the chromosomes
with the highest percentage of correlated genes (1q, 8p, 8q, 16p,
16q, 17q, and 20q) were also the most frequent sites of genomic alterations
in breast cancer. Our analysis showed that several known breast tumor
amplicons (at 8p11-p12, 11q13, and 17q12) are located within clusters
of genes with correlated expression. Using hierarchical clustering
on samples and a Treeview representation of whole chromosome arms,
we observed a higher-order organization of correlated genes, sometimes
involving very large chromosomal domains that could extend to a whole
chromosome arm. Transcription correlation maps are a new way of visualizing
transcriptome data. They will help to identify new genes involved
in tumor progression and new mechanisms of gene regulation in tumors.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/4/1376}
}
@ARTICLE{Reyes2008,
author = {Reyes, Jeannie H. and O'Shea, K. Sue and Wys, Noel L. and Velkey,
J. Matthew and Prieskorn, Diane M. and Wesolowski, Karolina and Miller,
Josef M. and Altschuler, Richard A.},
title = {Glutamatergic Neuronal Differentiation of Mouse Embryonic Stem Cells
after Transient Expression of Neurogenin 1 and Treatment with BDNF
and GDNF: In Vitro and In Vivo Studies},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {12622--12631},
number = {48},
month = nov,
abstract = {Differentiation of the pluripotent neuroepithelium into neurons and
glia is accomplished by the interaction of growth factors and cell-type
restricted transcription factors. One approach to obtaining a particular
neuronal phenotype is by recapitulating the expression of these factors
in embryonic stem (ES) cells. Toward the eventual goal of auditory
nerve replacement, the aim of the current investigation was to generate
auditory nerve-like glutamatergic neurons from ES cells. Transient
expression of Neurog1 promoted widespread neuronal differentiation
in vitro; when supplemented with brain-derived neurotrophic factor
(BDNF) and glial cell line-derived neurotrophic factor (GDNF), 75%
of ES cell-derived neurons attained a glutamatergic phenotype after
5 d in vitro. Mouse ES cells were also placed into deafened guinea
pig cochleae and Neurog1 expression was induced for 48 h followed
by 26 d of BDNF/GDNF infusion. In vivo differentiation resulted in
50-75% of ES cells bearing markers of early neurons, and a majority
of these cells had a glutamatergic phenotype. This is the first study
to report a high percentage of ES cell differentiation into a glutamatergic
phenotype and sets the stage for cell replacement of auditory nerve.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/48/12622}
}
@ARTICLE{Reyes-Bermudez2009,
author = {Reyes-Bermudez, Alejandro and DeSalvo, Michael K. and Voolstra, Christian
R. and Sunagawa, Shinichi and Szmant, Alina M. and Iglesias-Prieto,
Roberto and Medina, Mónica},
title = {Gene expression microarray analysis encompassing metamorphosis and
the onset of calcification in the scleractinian coral Montastraea
faveolata},
journal = {Marine Genomics},
year = {2009},
volume = {2},
pages = {149--159},
number = {3-4},
month = sep,
abstract = {Abstract Similar to many marine invertebrates, scleractinian corals
experience a dramatic morphological transformation, as well as a
habitat switch, upon settlement and metamorphosis. At this time,
planula larvae transform from non-calcifying, demersal, motile organisms
into sessile, calcifying, benthic juvenile polyps. We performed gene
expression microarray analyses between planulae, aposymbiotic primary
polyps, and symbiotic adult tissue to elucidate the molecular mechanisms
underlying coral metamorphosis and early stages of calcification
in the Robust/Short clade scleractinian coral Montastraea faveolata.
Among the annotated genes, the most abundant upregulated transcripts
in the planula stage are involved in protein synthesis, chromatin
assembly and mitochondrial metabolism; the polyp stage, morphogenesis,
protein catabolism and organic matrix synthesis; and the adult stage,
sexual reproduction, stress response and symbiosis. We also present
evidence showing that the planula and adult transcriptomes are more
similar to each other than to the polyp transcriptome. Our results
also point to a large number of uncharacterized adult coral-specific
genes likely involved in coral-specific functions such as symbiosis
and calcification.},
issn = {1874-7787},
keywords = {Microarray, Coral, Calcification, Metamorphosis, Transcriptomics},
url = {http://www.sciencedirect.com/science/article/B8JG7-4X49N4M-1/2/ed37d5bc65f4b8987a35376be56db124}
}
@ARTICLE{Reymann2008,
author = {Reymann, Susanne and Borlak, Jürgen},
title = {Transcription profiling of lung adenocarcinomas of c-myc-transgenic
mice: Identification of the c-myc regulatory gene network},
journal = {BMC Systems Biology},
year = {2008},
volume = {2},
pages = {46},
number = {1},
abstract = {BACKGROUND:The transcriptional regulator c-Myc is the most frequently
deregulated oncogene in human tumors. Targeted overexpression of
this gene in mice results in distinct types of lung adenocarcinomas.
By using microarray technology, alterations in the expression of
genes were captured based on a female transgenic mouse model in which,
indeed, c-Myc overexpression in alveolar epithelium results in the
development of bronchiolo-alveolar carcinoma (BAC) and papillary
adenocarcinoma (PLAC). In this study, we analyzed exclusively the
promoters of induced genes by different in silico methods in order
to elucidate the c-Myc transcriptional regulatory network.RESULTS:We
analyzed the promoters of 361 transcriptionally induced genes with
respect to c-Myc binding sites and found 110 putative binding sites
in 94 promoters. Furthermore, we analyzed the flanking sequences
(+/- 100 bp) around the 110 c-Myc binding sites and found Ap2, Zf5,
Zic3, and E2f binding sites to be overrepresented in these regions.
Then, we analyzed the promoters of 361 induced genes with respect
to binding sites of other transcription factors (TFs) which were
upregulated by c-Myc overexpression. We identified at least one binding
site of at least one of these TFs in 220 promoters, thus elucidating
a potential transcription factor network. The analysis correlated
well with the significant overexpression of the TFs Atf2, Foxf1a,
Smad4, Sox4, Sp3 and Stat5a. Finally, we analyzed promoters of regulated
genes which where apparently not regulated by c-Myc or other c-Myc
targeted TFs and identified overrepresented Oct1, Mzf1, Ppargamma,
Plzf, Ets, and HmgIY binding sites when compared against control
promoter background.CONCLUSION:Our in silico data suggest a model
of a transcriptional regulatory network in which different TFs act
in concert upon c-Myc overexpression. We determined molecular rules
for transcriptional regulation to explain, in part, the carcinogenic
effect seen in mice overexpressing the c-Myc oncogene.},
doi = {10.1186/1752-0509-2-46},
issn = {1752-0509},
pubmedid = {18498649},
url = {http://www.biomedcentral.com/1752-0509/2/46}
}
@ARTICLE{Reymann2008a,
author = {Reymann, Susanne and Borlak, Jürgen},
title = {Topoisomerase II inhibition involves characteristic chromosomal expression
patterns},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {324},
number = {1},
abstract = {BACKGROUND:The phenomenon of co-localization of transcriptionally
upregulated genes showing similar expression levels is known across
all eukaryotic genomes. We recently mapped the Aroclor 1254-regulated
transcriptome back onto the genome and provided evidence for the
statistically significant co-localization of regulated genes. They
did, however, not always show similar expression levels, and many
of the regulated genes were, in fact, repressed.RESULTS:In this study,
we were able to reproduce this observation with microarray data stemming
from 1) human hepatocytes treated with the gyrase and potential topoisomerase
II inhibitor trovafloxacin, 2) human hepatocytes treated with the
topoisomerase II inhibitor doxorubicin and 3) mouse lymphoma cells
treated with the topoisomerase II inhibitor etoposide. We found statistically
significant co-localization of regulated gene pairs – induced and
repressed – within the window size of 0–100 kbp. Notably, by using
microarray data stemming from lung tissue of a mouse transgenic line
overexpressing the transcription factor c-myc, which served as a
negative control, we found regulated genes to be located with regard
to each other nearly in the same way as genes distributed randomly
all over the genome (0–100 kbp).CONCLUSION:We suggest topoisomerase
II inhibition by Aroclor 1254, trovafloxacin, doxorubicin, and etoposide
to be responsible for significant co-localization of regulated genes
through the inability of the stabilized enzyme complexes to religate
DNA. Within the permanently opened chromatin domains, neighbored
genes might be allowed to be regulated. Overexpression of c-myc,
however, does not inhibit topoisomerase II activity. Consequently,
the enzyme is able to perform its normal function of transiently
breaking and rejoining the DNA double strand. As a result, exclusively
target genes are regulated.},
doi = {10.1186/1471-2164-9-324},
issn = {1471-2164},
pubmedid = {18611269},
url = {http://www.biomedcentral.com/1471-2164/9/324}
}
@ARTICLE{Reyna2008,
author = {Reyna, Sara M. and Ghosh, Sangeeta and Tantiwong, Puntip and Meka,
C.S. Reddy and Eagan, Phyllis and Jenkinson, Christopher P. and Cersosimo,
Eugenio and DeFronzo, Ralph A. and Coletta, Dawn K. and Sriwijitkamol,
Apiradee and Musi, Nicolas},
title = {Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle
From Insulin-Resistant Subjects},
journal = {Diabetes},
year = {2008},
volume = {57},
pages = {2595--2602},
number = {10},
month = oct,
abstract = {OBJECTIVE-- Tall-like receptor (TLR)4 has been implicated in the pathogenesis
of free fatty acid (FFA)-induced insulin resistance by activating
inflammatory pathways, including inhibitor of {kappa}B (I{kappa}B)/nuclear
factor {kappa}B (NF{kappa}B). However, it is not known whether insulin-resistant
subjects have abnormal TLR4 signaling. We examined whether insulin-resistant
subjects have abnormal TLR4 expression and TLR4-driven (I{kappa}B/NF{kappa}B)
signaling in skeletal muscle. RESEARCH DESIGN AND METHODS-- TLR4
gene expression and protein content were measured in muscle biopsies
in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human
myotube culture system was used to examine whether FFAs stimulate
I{kappa}B/NF{kappa}B via TLR4 and whether FFAs increase TLR4 expression/content
in muscle. RESULTS-- Obese and type 2 diabetic subjects had significantly
elevated TLR4 gene expression and protein content in muscle. TLR4
muscle protein content correlated with the severity of insulin resistance.
Obese and type 2 diabetic subjects also had lower I{kappa}B{alpha}
content, an indication of elevated I{kappa}B/NF{kappa}B signaling.
The increase in TLR4 and NF{kappa}B signaling was accompanied by
elevated expression of the NF{kappa}B-regulated genes interleukin
(IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes,
acute palmitate treatment stimulated I{kappa}B/NF{kappa}B, and blockade
of TLR4 prevented the ability of palmitate to stimulate the I{kappa}B/NF{kappa}B
pathway. Increased TLR4 content and gene expression observed in muscle
from insulin-resistant subjects were reproduced by treating myotubes
from lean, normal-glucose-tolerant subjects with palmitate. Palmitate
also increased IL-6 and SOD2 gene expression, and this effect was
prevented by inhibiting NF{kappa}B. CONCLUSIONS-- Abnormal TLR4 expression
and signaling, possibly caused by elevated plasma FFA levels, may
contribute to the pathogenesis of insulin resistance in humans.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/57/10/2595}
}
@ARTICLE{Reynies2009,
author = {de Reynies, Aurelien and Assie, Guillaume and Rickman, David S. and
Tissier, Frederique and Groussin, Lionel and Rene-Corail, Fernande
and Dousset, Bertrand and Bertagna, Xavier and Clauser, Eric and
Bertherat, Jerome},
title = {Gene Expression Profiling Reveals a New Classification of Adrenocortical
Tumors and Identifies Molecular Predictors of Malignancy and Survival},
journal = {J. Clin. Oncol.},
year = {2009},
volume = {27},
pages = {1108--1115},
number = {7},
month = mar,
abstract = {PurposeAdrenocortical tumors, especially cancers, remain challenging
both for their diagnosis and prognosis assessment. The aim of this
article is to identify molecular predictors of malignancy and of
survival. Patients and MethodsOne hundred fifty-three unilateral
adrenocortical tumors were studied by microarray (n = 92) or reverse
transcription quantitative polymerase chain reaction (n = 148). A
two-gene predictor of malignancy was built using the disease-free
survival as the end point in a training cohort (n = 47), then validated
in an independent validation cohort (n = 104). The best candidate
genes were selected using Cox models, and the best gene combination
was validated using the log-rank test. Similarly, for malignant tumors,
a two-gene predictor of survival was built using the overall survival
as the end point in a training cohort (n = 23), then tested in an
independent validation cohort (n = 35). ResultsUnsupervised clustering
analysis discriminated robustly the malignant and benign tumors,
and identified two groups of malignant tumors with very different
outcome. The combined expression of DLG7 and PINK1 was the best predictor
of disease-free survival (log-rank P {approx} 10-12), could overcome
the uncertainties of intermediate pathological Weiss scores, and
remained significant after adjustment to the Weiss score (P < 1.3
x 10-2). Among the malignant tumors, the combined expression of BUB1B
and PINK1 was the best predictor of overall survival (P < 2 x 10-6),
and remained significant after adjusting for MacFarlane staging (P
< .005). ConclusionGene expression analysis unravels two distinct
groups of adrenocortical carcinomas. The molecular predictors of
malignancy and of survival are reliable and provide valuable independent
information in addition to pathology and tumor staging. These original
tools should provide important improvements for adrenal tumors management.},
url = {http://jco.ascopubs.org/cgi/content/abstract/27/7/1108}
}
@ARTICLE{Reynolds2006,
author = {Reynolds, Angela and Anderson, Emily M. and Vermeulen, Annaleen and
Fedorov, Yuriy and Robinson, Kathryn and Leake, Devin and Karpilow,
Jon and Marshall, William S. and Khvorova, Anastasia},
title = {Induction of the interferon response by siRNA is cell type- and duplex
length-dependent},
journal = {RNA},
year = {2006},
volume = {12},
pages = {988--993},
number = {6},
month = jun,
abstract = {Long (27-29-bp dsRNA) Dicer-dependent substrates have been identified
as potent mediators of RNAi-induced gene knockdown in HEK293 and
HeLa cells. As the lengths of these molecules are reported to be
below the threshold generally regarded as necessary for induction
of the mammalian interferon (IFN) response, these long siRNA are
being considered as RNAi substrates in both research and therapeutic
settings. In this report, we demonstrate that >23-bp dsRNA can influence
cell viability and induce a potent IFN response (highlighted by a
strong up-regulation of the dsRNA receptor, Toll-like receptor 3)
in a cell type-specific manner. This finding suggests that the length
threshold for siRNA induction of the IFN response is not fixed but
instead varies significantly among different cell types. Given the
diversity of cell types that comprise whole organisms, these findings
suggest great care should be taken when considering length variations
of dsRNA molecules for RNAi experimentation, especially in therapeutic
applications.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/12/6/988}
}
@ARTICLE{Rhazi2009,
author = {Rhazi, L. and Bodard, A.-L. and Fathollahi, B. and Aussenac, T.},
title = {High throughput microchip-based separation and quantitation of high-molecular-weight
glutenin subunits},
journal = {Journal of Cereal Science},
year = {2009},
volume = {49},
pages = {272--277},
number = {2},
month = mar,
abstract = {Knowledge of glutenin subunit composition is important for the prediction
of the genetic potential of breeding lines as these proteins are
known to be responsible for the main differences in bread-making
quality. In this study, a commercial high throughput microchip capillary
electrophoresis-sodium dodecyl sulfate (microchip CE) platform, LabChip
90, was evaluated for qualitative and quantitative analyses of HMW-GS.
130 French common wheat varieties of known composition were analyzed
for rapid identification and the allocation of individual HMW-GS.
In addition, the HMW-GS were individually quantified and the ratio
of HMW-GS to LMW-GS was determined for genotype comparison. The microchip
CE analysis provides comparable resolution and sensitivity to conventional
RP-HPLC for identification of the HMW-GS but at a time scale of approximately
100 times faster (45 s per sample analysis versus 80 min for RP-HPLC).
The results show that the high throughput microchip CE method can
be used for routine identification and quantitation of glutenin subunits,
in particular for screening wheat quality and wheat cultivar development
activities where large numbers of samples are to be evaluated.},
issn = {0733-5210},
keywords = {Wheat, Glutenin subunits, Microchip, Lab-on-a-chip},
url = {http://www.sciencedirect.com/science/article/B6WHK-4V1KMNM-1/2/479b97d3cc6fb94f91aae55657fcdd39}
}
@ARTICLE{Rheault2010,
author = {Rheault, Michelle N. and Kren, Stefan M. and Hartich, Linda A. and
Wall, Melanie and Thomas, William and Mesa, Hector A. and Avner,
Philip and Lees, George E. and Kashtan, Clifford E. and Segal, Yoav},
title = {X-inactivation modifies disease severity in female carriers of murine
X-linked Alport syndrome},
journal = {Nephrol. Dial. Transplant.},
year = {2010},
volume = {25},
pages = {764--769},
number = {3},
month = mar,
abstract = {Background. Female carriers of X-linked Alport syndrome (XLAS) demonstrate
variability in clinical phenotype that, unlike males, cannot be correlated
with genotype. X-inactivation, the method by which females (XX) silence
transcription from one X chromosome in order to achieve gene dosage
parity with males (XY), likely modifies the carrier phenotype, but
this hypothesis has not been tested directly. Methods. Using a genetically
defined mouse model of XLAS, we generated two groups of Alport female
(Col4a5+/-) carriers that differed only in the X-controlling element
(Xce) allele regulating X-inactivation. We followed the groups as
far as 6 months of age comparing survival and surrogate outcome measures
of urine protein and plasma urea nitrogen. Results. Preferential
inactivation of the mutant Col4a5 gene improved survival and surrogate
outcome measures of urine protein and plasma urea nitrogen. In studies
of surviving mice, we found that X-inactivation in kidney, measured
by allele-specific mRNA expression assays, correlated with surrogate
outcomes. Conclusions. Our findings establish X-inactivation as a
major modifier of the carrier phenotype in X-linked Alport syndrome.
Thus, X-inactivation patterns may offer prognostic information and
point to possible treatment strategies for symptomatic carriers.},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/25/3/764}
}
@ARTICLE{Rhee2008,
author = {Rhee, Dong Keun and Park, Su Hyung and Jang, Yeun Kyu},
title = {Molecular signatures associated with transformation and progression
to breast cancer in the isogenic MCF10 model},
journal = {Genomics},
year = {2008},
volume = {92},
pages = {419--428},
number = {6},
month = dec,
abstract = {Comparative microarray analyses provided insight into understanding
transcript changes during cancer progression; however, a reproducible
signature underlying breast carcinogenesis has yet to be little available.
We utilized gene expression profiling to define molecular signatures
associated with transformation and cancer progression in a series
of isogenic human breast cancer cell lines including a normal, benign,
noninvasive and invasive carcinoma. Clustering analysis revealed
four distinct expression patterns based on upregulation or downregulation
patterns. These profiles proved quite useful for describing breast
cancer tumorigenesis and invasiveness. Downregulation of TNFSF7,
S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family),
and upregulation of kallikrein-5 and thrombospondin-1 were associated
with transformation and progression of breast cancer cells. Importantly,
downregulation of the genes was reversed by treatment with silencing
inhibitors, implying the potential roles of epigenetic inactivation
in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9
inhibit growth in benign and noninvasive carcinoma cells, suggesting
their negative role in cell proliferation. The data presented here
may facilitate the identification and functional analyses of prognostic
biomarkers for breast cancer.},
issn = {0888-7543},
keywords = {Isogenic human breast cancer cell lines, Epigenetic inactivation,
S100 calcium-binding protein family, Progression, Transformation,
Molecular signatures},
url = {http://www.sciencedirect.com/science/article/B6WG1-4TMRK14-1/2/debdda2e2cdca24f686a581e0a73e1ce}
}
@ARTICLE{Rhee2011,
author = {Ho Sung Rhee and B. Franklin Pugh},
title = {Comprehensive Genome-wide Protein-DNA Interactions Detected at Single-Nucleotide
Resolution},
journal = {Cell},
year = {2011},
volume = {147},
pages = {1408 - 1419},
number = {6},
abstract = {Summary Chromatin immunoprecipitation (ChIP-chip and ChIP-seq) assays
identify where proteins bind throughout a genome. However, DNA contamination
and DNA fragmentation heterogeneity produce false positives (erroneous
calls) and imprecision in mapping. Consequently, stringent data filtering
produces false negatives (missed calls). Here we describe ChIP-exo,
where an exonuclease trims ChIP DNA to a precise distance from the
crosslinking site. Bound locations are detectable as peak pairs by
deep sequencing. Contaminating DNA is degraded or fails to form complementary
peak pairs. With the single bp accuracy provided by ChIP-exo, we
show an unprecedented view into genome-wide binding of the yeast
transcription factors Reb1, Gal4, Phd1, Rap1, and human CTCF. Each
of these factors was chosen to address potential limitations of ChIP-exo.
We found that binding sites become unambiguous and reveal diverse
tendencies governing in vivo DNA-binding specificity that include
sequence variants, functionally distinct motifs, motif clustering,
secondary interactions, and combinatorial modules within a compound
motif.},
doi = {10.1016/j.cell.2011.11.013},
issn = {0092-8674},
url = {http://www.sciencedirect.com/science/article/pii/S0092867411013511}
}
@ARTICLE{Rhee2012,
author = {Jae-Sung Rhee and Bo-Mi Kim and Beom-Soon Choi and Jae-Seong Lee},
title = {Expression pattern analysis of DNA repair-related and DNA damage
response genes revealed by 55\&xa0;K oligomicroarray upon UV-B irradiation
in the intertidal copepod, Tigriopus japonicus},
journal = {Comparative Biochemistry and Physiology Part C: Toxicology \&
Pharmacology},
year = {2012},
volume = {155},
pages = {359 - 368},
number = {2},
abstract = {Ultraviolet-B (UV-B) radiation affects the genome stability of aquatic
organisms by absorption of certain wavelength at the molecular level.
Recently, extensive gene information has been identified from the
intertidal copepod, Tigriopus japonicus. Here, we developed a 55 K
(54,254 genes) oligomicroarray and tested its usefulness to identify
the effect of single dose of UV-B irradiation (12 kJ/m2) on
transcriptomes of the copepod T. japonicus. A total of 35,361 spots
were identified to be significantly modulated on the 55 K oligomicroarray
by hierarchical clustering after exposure to UV-B irradiation over
48 h (6, 12, 24, and 48 h). Of them, 1300 and 588 genes
were observed to be up-regulated and down-regulated at all time points,
respectively. Particularly, it was observed that several genes involved
in DNA repair mechanism were significantly modulated in the UV-B-exposed
T. japonicus by microarray and quantitative real-time RT-PCR analysis.
In detail, UV-B irradiation specifically up-regulated some genes
in non-homologous end-joining (NHEJ), homologous recombination (HR),
base excision repair (BER), and mismatch repair (MMR) pathways. On
the other hand, a majority of down-regulated genes were representatives
for the nucleotide excision repair (NER) mechanism. These results
demonstrated that DNA damage would be induced by UV-B irradiation
in this species, resulting in reliable induction or repression of
various DNA repair mechanism on UV-B-induced DNA damage. In this
report, we suggest that a high density microarray-based approach
for risk assessment of UV-B irradiation would be useful to elucidate
the mechanistic analysis in a non-model organism. This study could
also provide a better understanding of molecular mechanisms of cellular
protection against UV-B-induced stress.},
doi = {10.1016/j.cbpc.2011.10.005},
issn = {1532-0456},
keywords = {Ultraviolet-B (UV-B)},
url = {http://www.sciencedirect.com/science/article/pii/S1532045611001967}
}
@ARTICLE{Rhee2007,
author = {Rhee, Kun Do and Ruiz, Alberto and Duncan, Jacque L. and Hauswirth,
William W. and LaVail, Matthew M. and Bok, Dean and Yang, Xian-Jie},
title = {Molecular and Cellular Alterations Induced by Sustained Expression
of Ciliary Neurotrophic Factor in a Mouse Model of Retinitis Pigmentosa},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {1389--1400},
number = {3},
month = mar,
abstract = {PURPOSE. To characterize molecular and cellular changes induced by
sustained expression of ciliary neurotrophic factor (CNTF) in the
rds mutant mouse retina. METHODS. Recombinant adeno-associated virus
(rAAV) expressing CNTF was injected subretinally, for transduction
of peripherin/rds+/- transgenic mice that carry the P216L mutation
found in human retinitis pigmentosa. Characterization of retinal
neurons and glia was performed by immunocytochemistry with cell-type-specific
markers. Activation of signaling molecules was examined by Western
blot and immunostaining. Alterations of gene transcription profiles
were studied by microarray analyses. RESULTS. CNTF viral transduction
maintained rhodopsin expression in surviving rod photoreceptors,
but greatly reduced both S- and M-opsin normally expressed in cones.
In addition, CNTF treatment resulted in increased numbers and dispersion
of Muller glia and Chx10-positive bipolar cells within the inner
nuclear layer. Persistent CNTF signaling also caused enhanced phosphorylation
of STAT1, STAT3, and p42/44 ERK, as well as their levels of expression.
Moreover, altered transcription profiles were detected for a large
number of genes. Among these, Crx and Nrl involved in photoreceptor
differentiation and several genes involved in phototransduction were
suppressed. CONCLUSIONS. Despite the rescue from cell death, continuous
exposure to CNTF changed photoreceptor cell profiles, especially
resulting in the loss of cone immunoreactivity. In addition, the
Muller glia and bipolar cells became disorganized, and the number
of cells expressing Muller and bipolar cell markers increased. Constitutive
CNTF production resulted in sustained activation of cytokine signal
transduction and altered the expression of a large number of genes.
Therefore, stringent regulation of CNTF may be necessary for its
therapeutic application in preventing retinal degeneration.},
url = {http://www.iovs.org/cgi/content/abstract/48/3/1389}
}
@ARTICLE{Rhee2005,
author = {Rhee, Sue J. and Walker, W. Allan and Cherayil, Bobby J.},
title = {Developmentally Regulated Intestinal Expression of IFN-{gamma} and
Its Target Genes and the Age-Specific Response to Enteric Salmonella
Infection},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {1127--1136},
number = {2},
month = jul,
abstract = {Young infants are highly susceptible to systemic dissemination of
enteric pathogens such as Salmonella typhimurium when compared with
older individuals. The mechanisms underlying this differential susceptibility
have not been defined clearly. To better understand this phenomenon,
we examined the responses of adult mice and preweaned pups to oral
infection by S. typhimurium. We found clear age-specific differences,
namely, an attenuated intestinal inflammatory response and a higher
systemic bacterial burden in the pups compared with the adults. To
elucidate the molecular basis for these differences, we obtained
a microarray-based profile of gene expression in the small intestines
of uninfected adult and preweaned animals. The results indicated
a striking age-dependent increase in the intestinal expression of
a number of IFN-{gamma}-regulated genes involved in antimicrobial
defense. This finding was confirmed by real-time quantitative PCR,
which also demonstrated an age-dependent increase in intestinal expression
of IFN-{gamma}. The developmental up-regulation of the IFN-{gamma}-regulated
genes was dependent on both IFN-{gamma} and a normal commensal microflora,
as indicated by experiments in IFN-{gamma}-knockout mice and germfree
mice, respectively. However, the increase in expression of IFN-{gamma}
itself was independent of the commensal flora. The functional importance
of IFN-{gamma} in the immunological maturation of the intestine was
confirmed by the observation that the response of adult IFN-{gamma}-knockout
animals to S. typhimurium infection resembled that of the wild-type
pups. Our findings thus reveal a novel role for IFN-{gamma} in the
developmental regulation of antimicrobial responses in the intestine.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/2/1127}
}
@ARTICLE{Rho2010,
author = {Rho, Hyun-Wook and Lee, Byoung-Chan and Choi, Eun-Seok and Choi,
Il-Ju and Lee, Yeon-Su and Goh, Sung-Ho},
title = {Identification of valid reference genes for gene expression studies
of human stomach cancer by reverse transcription-qPCR},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {240},
number = {1},
abstract = {BACKGROUND:Reverse transcription quantitative real-time polymerase
chain reaction (RT-qPCR) is a powerful method for the analysis of
gene expression. Target gene expression levels are usually normalized
to a consistently expressed reference gene also known as internal
standard, in the same sample. However, much effort has not been expended
thus far in the search for reference genes suitable for the study
of stomach cancer using RT-qPCR, although selection of optimal reference
genes is critical for interpretation of results.METHODS:We assessed
the suitability of six possible reference genes, beta-actin (ACTB),
glyceraldehydes-3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyl
transferase 1 (HPRT1), beta-2-microglobulin (B2M), ribosomal subunit
L29 (RPL29) and 18S ribosomal RNA (18S rRNA) in 20 normal and tumor
stomach tissue pairs of stomach cancer patients and 6 stomach cancer
cell lines, by RT-qPCR. Employing expression stability analyses using
NormFinder and geNorm algorithms we determined the order of performance
of these reference genes and their variation values.RESULTS:This
RT-qPCR study showed that there are statistically significant (p
< 0.05) differences in the expression levels of HPRT1 and 18S rRNA
in 'normal-' versus 'tumor stomach tissues'. The stability analyses
by geNorm suggest B2M-GAPDH, as best reference gene combination for
'stomach cancer cell lines'; RPL29-HPRT1, for 'all stomach tissues';
and ACTB-18S rRNA, for 'all stomach cell lines and tissues'. NormFinder
also identified B2M as the best reference gene for 'stomach cancer
cell lines', RPL29-B2M for 'all stomach tissues', and 18S rRNA-ACTB
for 'all stomach cell lines and tissues'. The comparisons of normalized
expression of the target gene, GPNMB, showed different interpretation
of target gene expression depend on best single reference gene or
combination.CONCLUSION:This study validated RPL29 and RPL29-B2M as
the best single reference genes and combination, for RT-qPCR analysis
of 'all stomach tissues', and B2M and B2M-GAPDH as the best single
reference gene and combination, for 'stomach cancer cell lines'.
Use of these validated reference genes should provide more exact
interpretation of differential gene expressions at transcription
level in stomach cancer.},
doi = {10.1186/1471-2407-10-240},
issn = {1471-2407},
pubmedid = {20507635},
url = {http://www.biomedcentral.com/1471-2407/10/240}
}
@ARTICLE{Rhoads2010,
author = {Rhoads, M.L. and Kim, J.W. and Collier, R.J. and Crooker, B.A. and
Boisclair, Y.R. and Baumgard, L.H. and Rhoads, R.P.},
title = {Effects of heat stress and nutrition on lactating Holstein cows:
II. Aspects of hepatic growth hormone responsiveness},
journal = {Journal of Dairy Science},
year = {2010},
volume = {93},
pages = {170--179},
number = {1},
month = jan,
abstract = {Heat stress (HS) is a multibillion-dollar problem for the global dairy
industry, and reduced milk yield is the primary contributor to this
annual economic loss. Feed intake declines precipitously during HS
but accounts for only about 35% of the decreased milk synthesis,
indicating that the physiological mechanisms responsible for decreased
milk production during HS are only partly understood. Thus, our experimental
objectives were to characterize the direct effects of HS on the somatotropic
axis, a primary regulator of metabolism and milk yield. We recently
reported no differences in mean growth hormone (GH) concentrations,
GH pulsatility characteristics, or GH response to growth hormone
releasing factor in HS versus pair-fed (PF) thermoneutral controls.
Despite similarities in circulating GH characteristics, plasma insulin-like
growth factor (IGF)-I concentrations were reduced during heat stress
conditions but not in PF animals, suggesting that uncoupling of the
hepatic GH-IGF axis may occur during HS. We investigated this possibility
by measuring proximal indicators of hepatic GH signaling following
a GH bolus. Heat stress but not PF decreased abundance of the GH
receptor and GH-dependent signal transducer and activator of transcription
(STAT)-5 phosphorylation. Consistent with reduced GH signaling through
STAT-5, basal hepatic IGF-I mRNA abundance was lower in HS cows.
Thus, the reduced hepatic GH responsiveness (in terms of IGF-I gene
expression) observed during HS appears to involve mechanisms at least
partially independent of reduced nutrient intake. The physiological
significance of reduced hepatic GH receptor abundance during HS is
unclear at this time. Aside from reducing IGF-I production, it may
reduce other GH-sensitive bioenergetic processes such as gluconeogenesis.},
issn = {0022-0302},
keywords = {heat stress, somatotropin, hyperthermia},
url = {http://www.sciencedirect.com/science/article/B9887-4Y0F5B4-T/2/9442ec75bbd1b2bc3adb8e1cc0b39afa}
}
@ARTICLE{Ria2009,
author = {Ria, Roberto and Todoerti, Katia and Berardi, Simona and Coluccia,
Addolorata Maria Luce and De Luisi, Annunziata and Mattioli, Michela
and Ronchetti, Domenica and Morabito, Fortunato and Guarini, Attilio
and Petrucci, Maria Teresa and Dammacco, Franco and Ribatti, Domenico
and Neri, Antonino and Vacca, Angelo},
title = {Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients
with Multiple Myeloma},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {5369--5378},
number = {17},
month = sep,
abstract = {Purpose: To determine a "gene/molecular fingerprint" of multiple myeloma
endothelial cells and identify vascular mechanisms governing the
malignant progression from quiescent monoclonal gammopathy of undetermined
significance. Experimental Design: Comparative gene expression profiling
of multiple myeloma endothelial cells and monoclonal gammopathy of
undetermined significance endothelial cells with the Affymetrix U133A
Arrays was carried out in patients at diagnosis; expression and function
of selective vascular markers was validated by real-time reverse
transcriptase-PCR, Western blot, and small interfering RNA analyses.
Results: Twenty-two genes were found differentially expressed (14
down-regulated and eight up-regulated) at relatively high stringency
in multiple myeloma endothelial cells compared with monoclonal gammopathy
of undetermined significance endothelial cells. Functional annotation
revealed a role of these genes in the regulation of extracellular
matrix formation and bone remodeling, cell adhesion, chemotaxis,
angiogenesis, resistance to apoptosis, and cell-cycle regulation.
Validation was focused on six genes (DIRAS3, SERPINF1, SRPX, BNIP3,
IER3, and SEPW1) not previously found to be functionally correlated
to the overangiogenic phenotype of multiple myeloma endothelial cells
in active disease. The small interfering RNA knockdown of BNIP3,
IER3, and SEPW1 genes affected critical multiple myeloma endothelial
cell functions correlated with the overangiogenic phenotype. Conclusions:
The distinct endothelial cell gene expression profiles and vascular
phenotypes detected in this study may influence remodeling of the
bone marrow microenvironment in patients with active multiple myeloma.
A better understanding of the linkage between plasma cells and endothelial
cells in multiple myeloma could contribute to the molecular classification
of the disease and thus pinpoint selective gene targets for more
effective antiangiogenic treatments. (Clin Cancer Res 2009;15(17):5369-78)},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/17/5369}
}
@ARTICLE{Ribas2009,
author = {Ribas, Antoni and Comin-Anduix, Begona and Chmielowski, Bartosz and
Jalil, Jason and de la Rocha, Pilar and McCannel, Tara A. and Ochoa,
Maria Teresa and Seja, Elizabeth and Villanueva, Arturo and Oseguera,
Denise K. and Straatsma, Bradley R. and Cochran, Alistair J. and
Glaspy, John A. and Hui, Liu and Marincola, Francesco M. and Wang,
Ena and Economou, James S. and Gomez-Navarro, Jesus},
title = {Dendritic Cell Vaccination Combined with CTLA4 Blockade in Patients
with Metastatic Melanoma},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {6267--6276},
number = {19},
month = oct,
abstract = {Purpose: Tumor antigen-loaded dendritic cells (DC) are believed to
activate antitumor immunity by stimulating T cells, and CTL-associated
antigen 4 (CTLA4)-blocking antibodies should release a key negative
regulatory pathway on T cells. The combination was tested in a phase
I clinical trial in patients with advanced melanoma. Experimental
Design: Autologous DC were pulsed with MART-126-35 peptide and administered
with a dose escalation of the CTLA4-blocking antibody tremelimumab.
Sixteen patients were accrued to five dose levels. Primary end points
were safety and immune effects; clinical efficacy was a secondary
end point. Results: Dose-limiting toxicities of grade 3 diarrhea
and grade 2 hypophysitis developed in two of three patients receiving
tremelimumab at 10 mg/kg monthly. Four patients had an objective
tumor response, two partial responses and two complete responses,
all melanoma free between 2 and 4 years after study initiation. There
was no difference in immune monitoring results between patients with
an objective tumor response and those without a response. Exploratory
gene expression analysis suggested that immune-related gene signatures,
in particular for B-cell function, may be important in predicting
response. Conclusion: The combination of MART-1 peptide-pulsed DC
and tremelimumab results in objective and durable tumor responses
at the higher range of the expected response rate with either agent
alone. (Clin Cancer Res 2009;15(19):6267-76)},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/19/6267}
}
@ARTICLE{Ribeiro2009,
author = {Ribeiro, Ana C. and Pfaff, Donald W. and Devidze, Nino},
title = {Estradiol modulates behavioral arousal and induces changes in gene
expression profiles in brain regions involved in the control of vigilance},
journal = {European Journal of Neuroscience},
year = {2009},
volume = {29},
pages = {795--801},
number = {4},
abstract = {Abstract Estrogens reduce lipocalin-type prostaglandin D synthase
(L-PGDS) expression in a region-dependent manner in the mouse preoptic
area (POA). This result linked sex hormones with sleep–wake cycle
regulation. In turn, the somnogenic effects of prostaglandin D2 have
been shown to be mediated via increases in adenosine, and a select
group of sleep-active ventrolateral preoptic nucleus (VLPO) neurons
are directly activated by adenosine 2A (A2A) agonists. We hypothesized
that increased arousal after estrogen administration is mediated
by a reduction of L-PGDS and lowered A2A receptor expression in the
POA. To test this hypothesis, running wheel activity (RWA) of ovariectomized
female mice treated with oil or different doses of estradiol benzoate
(EB) was studied, followed by quantitative reverse-transcriptase
polymerase chain reaction to determine mRNA expression of genes related
to sleep and arousal in brain region extracts from oil-treated and
EB-treated mice. RWA was increased in estrogen-treated mice, and
these effects followed an inverted-U dose–response curve. The most
effective dose (1.25 μg EB/capsule) increased RWA more than 2.5-fold,
as compared with control animals, and EB doses that were higher or
lower were less effective. Increases in RWA were accompanied by decreased
L-PGDS mRNA in the POA and decreased A2A receptor mRNA in the POA
and VLPO. Given that EB-treated animals have higher motor activity
and lower levels of L-PGDS and A2A receptor mRNAs in sleep-active
areas, these correlational findings support the hypothesis that EB
may increase behavioral arousal by decreasing the levels of well-known
sleep-inducing molecules within the preoptic region.},
issn = {1460-9568},
keywords = {adenosine 2A, estrogens, mice, prostaglandin D2, sleep},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2009.06620.x}
}
@ARTICLE{Ribeiro-Silva2007,
author = {Ribeiro-Silva, Alfredo and Zhang, Haiyu and Jeffrey, Stefanie},
title = {RNA extraction from ten year old formalin-fixed paraffin-embedded
breast cancer samples: a comparison of column purification and magnetic
bead-based technologies},
journal = {BMC Molecular Biology},
year = {2007},
volume = {8},
pages = {118},
number = {1},
abstract = {BACKGROUND:The development of protocols for RNA extraction from paraffin-embedded
samples facilitates gene expression studies on archival samples with
known clinical outcome. Older samples are particularly valuable because
they are associated with longer clinical follow up. RNA extracted
from formalin-fixed paraffin-embedded (FFPE) tissue is problematic
due to chemical modifications and continued degradation over time.
We compared quantity and quality of RNA extracted by four different
protocols from 14 ten year old and 14 recently archived (three to
ten months old) FFPE breast cancer tissues. Using three spin column
purification-based protocols and one magnetic bead-based protocol,
total RNA was extracted in triplicate, generating 336 RNA extraction
experiments. RNA fragment size was assayed by reverse transcription-polymerase
chain reaction (RT-PCR) for the housekeeping gene glucose-6-phosphate
dehydrogenase (G6PD), testing primer sets designed to target RNA
fragment sizes of 67 bp, 151 bp, and 242 bp.RESULTS:Biologically
useful RNA (minimum RNA integrity number, RIN, 1.4) was extracted
in at least one of three attempts of each protocol in 86–100% of
older and 100% of recently archived ("months old") samples. Short
RNA fragments up to 151 bp were assayable by RT-PCR for G6PD in all
ten year old and months old tissues tested, but none of the ten year
old and only 43% of months old samples showed amplification if the
targeted fragment was 242 bp.CONCLUSION:All protocols extracted RNA
from ten year old FFPE samples with a minimum RIN of 1.4. Gene expression
of G6PD could be measured in all samples, old and recent, using RT-PCR
primers designed for RNA fragments up to 151 bp. RNA quality from
ten year old FFPE samples was similar to that extracted from months
old samples, but quantity and success rate were generally higher
for the months old group. We preferred the magnetic bead-based protocol
because of its speed and higher quantity of extracted RNA, although
it produced similar quality RNA to other protocols. If a chosen protocol
fails to extract biologically useful RNA from a given sample in a
first attempt, another attempt and then another protocol should be
tried before excluding the case from molecular analysis.},
doi = {10.1186/1471-2199-8-118},
issn = {1471-2199},
owner = {Meike Kuschel},
pubmedid = {18154675},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2199/8/118}
}
@ARTICLE{Ribes2007,
author = {Ribes, Vanessa and Otto, Diana M.E. and Dickmann, Leslie and Schmidt,
Katy and Schuhbaur, Brigitte and Henderson, Colin and Blomhoff, Rune
and Wolf, C. Roland and Tickle, Cheryll and Dollé, Pascal},
title = {Rescue of cytochrome P450 oxidoreductase (Por) mouse mutants reveals
functions in vasculogenesis, brain and limb patterning linked to
retinoic acid homeostasis},
journal = {Developmental Biology},
year = {2007},
volume = {303},
pages = {66--81},
number = {1},
month = mar,
abstract = {Cytochrome P450 oxidoreductase (POR) acts as an electron donor for
all cytochrome P450 enzymes. Knockout mouse Por-/- mutants, which
are early embryonic (E9.5) lethal, have been found to have overall
elevated retinoic acid (RA) levels, leading to the idea that POR
early developmental function is mainly linked to the activity of
the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol.
23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene,
we show that Por-/- embryos exhibit both elevated and ectopic RA
signaling activity e.g. in cephalic and caudal tissues. Two strategies
were used to functionally demonstrate that decreasing retinoid levels
can reverse Por-/- phenotypic defects, (i) by culturing Por-/- embryos
in defined serum-free medium, and (ii) by generating compound mutants
defective in RA synthesis due to haploinsufficiency of the retinaldehyde
dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the
Por-/- early phenotype, the latter allowing mutants to be recovered
up until E13.5. Abnormal brain patterning, with posteriorization
of hindbrain cell fates and defective mid- and forebrain development
and vascular defects were rescued in E9.5 Por-/- embryos. E13.5 Por-/-;
Raldh2+/- embryos exhibited abdominal/caudal and limb defects that
strikingly phenocopy those of Cyp26a1-/- and Cyp26b1-/- mutants,
respectively. Por-/-; Raldh2+/- limb buds were truncated and proximalized
and the anterior-posterior patterning system was not established.
Thus, POR function is indispensable for the proper regulation of
RA levels and tissue distribution not only during early embryonic
development but also in later morphogenesis and molecular patterning
of the brain, abdominal/caudal region and limbs.},
issn = {0012-1606},
keywords = {POR, Retinoids, P450 cytochromes, CYP enzymes, Limb development, Brain
patterning, Vasculogenesis},
url = {http://www.sciencedirect.com/science/article/B6WDG-4M6HY96-2/2/49263b2fcfee9c08c3b31e3acdf60121}
}
@ARTICLE{Ricciardelli2010,
author = {Ricciardelli, Carmela and Bianco-Miotto, Tina and Jindal, Shalini
and Dodd, Thomas J. and Cohen, Penelope A. and Marshall, Villis R.
and Sutherland, Peter D. and Samaratunga, Hemamali and Kench, James
G. and Dong, Ying and Wang, Hong and Clements, Judith A. and Risbridger,
Gail P. and Sutherland, Robert L. and Tilley, Wayne D. and Horsfall,
David J. and for the Australian Prostate Cancer BioResource},
title = {Comparative Biomarker Expression and RNA Integrity in Biospecimens
Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies},
journal = {Cancer Epidemiol. Biomarkers Prev.},
year = {2010},
volume = {19},
pages = {1755--1765},
number = {7},
month = jul,
abstract = {Background: Knowledge of preanalytic conditions that biospecimens
are subjected to is critically important because novel surgical procedures,
tissue sampling, handling, and storage might affect biomarker expression
or invalidate tissue samples as analytes for some technologies. Methods:
We investigated differences in RNA quality, gene expression by quantitative
real-time PCR, and immunoreactive protein expression of selected
prostate cancer biomarkers between tissues from retropubic radical
prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy
(RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples
were stained with antibodies to androgen receptor (AR) and prostate-specific
antigen (PSA) as intersite controls, and 14 other candidate biomarkers
of research interest to three laboratories within the Australian
Prostate Cancer BioResource tissue banking network. Quantitative
real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A
on RNA extracted from five RALP and five RRP frozen tissue cores.
Results: No histologic differences were observed between RALP and
RRP tissue. Biomarker staining grouped these samples into those with
increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or
no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1,
p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP
tissue. No difference in RNA quality or gene expression was detected
between RALP and RRP tissue. Conclusions: Changes in biomarker expression
between RALP and RRP tissue exist at the immunoreactive protein level,
but the etiology is unclear. Impact: Future studies should account
for changes in biomarker expression when using RALP tissues, and
mixed cohorts of RALP and RRP tissue should be avoided. Cancer Epidemiol
Biomarkers Prev; 19(7); 1755-65. (C)2010 AACR.},
url = {http://cebp.aacrjournals.org/cgi/content/abstract/19/7/1755}
}
@ARTICLE{Ricciardi2008,
author = {Ricciardi, Annamaria and Elia, Angela Rita and Cappello, Paola and
Puppo, Maura and Vanni, Cristina and Fardin, Paolo and Eva, Alessandra
and Munroe, David and Wu, Xiaolin and Giovarelli, Mirella and Varesio,
Luigi},
title = {Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of
Chemokine/Receptor Expression},
journal = {Mol. Cancer Res.},
year = {2008},
volume = {6},
pages = {175--185},
number = {2},
month = feb,
abstract = {Hypoxia is a condition of low oxygen tension occurring in inflammatory
tissues. Dendritic cells (DC) are professional antigen-presenting
cells whose differentiation, migration, and activities are intrinsically
linked to the microenvironment. DCs will home and migrate through
pathologic tissues before reaching their final destination in the
lymph node. We studied the differentiation of human monocytes into
immature DCs (iDCs) in a hypoxic microenvironment. We generated iDC
in vitro under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and
examined the hypoxia-responsive element in the promoter, gene expression,
and biochemical KEGG pathways. Hi-DCs had an interesting phenotype
represented by up-regulation of genes associated with cell movement/migration.
In addition, the Hi-DC cytokine/receptor pathway showed a dichotomy
between down-regulated chemokines and up-regulated chemokine receptor
mRNA expression. We showed that CCR3, CX3CR1, and CCR2 are hypoxia-inducible
genes and that CCL18, CCL23, CCL26, CCL24, and CCL14 are inhibited
by hypoxia. A strong chemotactic response to CCR2 and CXCR4 agonists
distinguished Hi-DCs from iDCs at a functional level. The hypoxic
microenvironment promotes the differentiation of Hi-DCs, which differs
from iDCs for gene expression profile and function. The most prominent
characteristic of Hi-DCs is the expression of a mobility/migratory
rather than inflammatory phenotype. We speculate that Hi-DCs have
the tendency to leave the hypoxic tissue and follow the chemokine
gradient toward normoxic areas where they can mature and contribute
to the inflammatory process. (Mol Cancer Res 2008;6(2):175-85)},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/6/2/175}
}
@ARTICLE{RiccA²2011,
author = {Raffaele Riccò and Anna Meneghello and Francesco Enrichi},
title = {Signal enhancement in DNA microarray using dye doped silica nanoparticles:
Application to Human Papilloma Virus (HPV) detection},
journal = {Biosensors and Bioelectronics},
year = {2011},
volume = {26},
pages = {2761 - 2765},
number = {5},
abstract = {DNA microarray is a powerful tool for the parallel of nucleic acids
and other biologically significant molecules. In this communication
we report an easy and cheap synthesis route for incorporating organic
dyes into monodisperse inorganic silica nanoparticles and their application
on the detection of carcinogenic risky Human Papilloma Virus using
DNA microarray technology. We correlate our system with conventional
direct dyes and commercial quantum dots, with a promising increase
in optical signal, and a related decrease of the limit of detection,
thus giving a remarkable improvement in this technique towards early
diagnosis of diseases and trace level detection of dangerous biological
contaminants.},
doi = {10.1016/j.bios.2010.10.024},
issn = {0956-5663},
keywords = {DNA microarray},
url = {http://www.sciencedirect.com/science/article/pii/S0956566310007098}
}
@ARTICLE{Rice2009,
author = {Rice, Kim L. and Hormaeche, Itsaso and Doulatov, Sergei and Flatow,
Jared M. and Grimwade, David and Mills, Ken I. and Leiva, Magdalena
and Ablain, Julien and Ambardekar, Charuta and McConnell, Melanie
J. and Dick, John E. and Licht, Jonathan D.},
title = {Comprehensive genomic screens identify a role for PLZF-RAR{alpha}
as a positive regulator of cell proliferation via direct regulation
of c-MYC},
journal = {Blood},
year = {2009},
volume = {114},
pages = {5499--5511},
number = {27},
month = dec,
abstract = {The t(11;17)(q23;q21) translocation is associated with a retinoic
acid (RA)-insensitive form of acute promyelocytic leukemia (APL),
involving the production of reciprocal fusion proteins, promyelocytic
leukemia zinc finger-retinoic acid receptor {alpha} (PLZF-RAR{alpha})
and RAR{alpha}-PLZF. Using a combination of chromatin immunoprecipitation
promotor arrays (ChIP-chip) and gene expression profiling, we identify
novel, direct target genes of PLZF-RAR{alpha} that tend to be repressed
in APL compared with other myeloid leukemias, supporting the role
of PLZF-RAR{alpha} as an aberrant repressor in APL. In primary murine
hematopoietic progenitors, PLZF-RAR{alpha} promotes cell growth,
and represses Dusp6 and Cdkn2d, while inducing c-Myc expression,
consistent with its role in leukemogenesis. PLZF-RAR{alpha} binds
to a region of the c-MYC promoter overlapping a functional PLZF site
and antagonizes PLZF-mediated repression, suggesting that PLZF-RAR{alpha}
may act as a dominant-negative version of PLZF by affecting the regulation
of shared targets. RA induced the differentiation of PLZF-RAR{alpha}-transformed
murine hematopoietic cells and reduced the frequency of clonogenic
progenitors, concomitant with c-Myc down-regulation. Surviving RA-treated
cells retained the ability to be replated and this was associated
with sustained c-Myc expression and repression of Dusp6, suggesting
a role for these genes in maintaining a self-renewal pathway triggered
by PLZF-RAR{alpha}.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/27/5499}
}
@ARTICLE{Rice2006,
author = {Rice, Suman and Mason, Helen D. and Whitehead, Saffron A.},
title = {Phytoestrogens and their low dose combinations inhibit mRNA expression
and activity of aromatase in human granulosa-luteal cells},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2006},
volume = {101},
pages = {216--225},
number = {4-5},
month = nov,
abstract = {There is evidence that certain phytoestrogens inhibit aromatase, the
enzyme that converts androgens to oestrogens. Kinetic studies in
cell-free preparations show that they may inhibit aromatase by competitive
binding to the enzyme, but there is a paucity of studies investigating
longer-term effects of phytoestrogens on the expression of steroidogenic
enzymes. This study tested the hypothesis that phytoestrogens could
reduce aromatase activity by down-regulation of its expression. Experiments
were carried out on primary cultures of human granulosa-luteal (GL)
cells after they had been exposed to phytoestrogens for 48 h. Aromatase
activity was measured by the ability of cells to convert testosterone
to estradiol over a 4 h period and aromatase mRNA expression (mRNAarom)
was subsequently measured from the same cells using quantitative
real-time PCR. The compounds investigated were the flavones, apigenin
and quercetin, and the isoflavones, genistein, biochanin A and daidzein
at doses of 10 [mu]M and 100 nM. Combinations of these compounds
at the lower dose were also investigated. All compounds tested dose-dependently
reduced mean mRNAarom compared with controls. Apigenin was the most
potent inhibitor with significant inhibition of mRNAarom seen at
both 10 [mu]M and 100 nM, whilst other flavonoids (except biochanin
A) only induced significant inhibition (p <= 0.05) at the higher
dose. Low dose (100 nM) mixtures of the compounds were ineffective
except for a combination of the three isoflavones that induced a
significant inhibition of mRNAarom. The changes in aromatase activity
paralleled the mRNAarom results and additional studies showed that
the reduction in aromatase activity was significantly delayed in
time compared with the reduction in mRNAarom. This is the first study
to compare the action of various phytoestrogens, either singly or
in low-dose combination, on the expression and activity of aromatase
in human cells and it suggests that chronic dietary exposure and
tissue accumulation of low-dose mixtures of phytoestrogens could
have important consequences for aromatase activity and the production
of oestrogens.},
issn = {0960-0760},
keywords = {Phytoestrogens, Aromatase, mRNA expression, Oestradiol},
url = {http://www.sciencedirect.com/science/article/B6T8X-4KVXPJY-3/2/8430888d5cee12be42b2032887660118}
}
@ARTICLE{Rice2007,
author = {Rice, Suman and Ojha, Kamal and Whitehead, Saffron and Mason, Helen},
title = {Stage-Specific Expression of Androgen Receptor, Follicle-Stimulating
Hormone Receptor, and Anti-Mullerian Hormone Type II Receptor in
Single, Isolated, Human Preantral Follicles: Relevance to Polycystic
Ovaries},
journal = {J. Clin. Endocrinol. Metab.},
year = {2007},
volume = {92},
pages = {1034--1040},
number = {3},
month = mar,
abstract = {Context: Recent evidence indicates that the increase in follicle numbers
seen in polycystic ovary syndrome occurs early in folliculogenesis,
with androgens being a likely causative candidate. In primates and
sheep, androgen excess in utero results in ovarian changes similar
to those in polycystic ovary syndrome. There is also increasing interest
in the role of anti-Mullerian hormone (AMH) in early folliculogenesis
because AMH knockout mice have an early depletion of their stock
of primordial follicles. Initiation and early folliculogenesis may
therefore be under negative control by AMH and positive control by
androgens. Objective: Because AMH signals exclusively through its
type II receptor (AMHRII), the aim of this study was to determine
and colocalize the stage-specific expression of AMHRII, androgen
receptor (AR), and FSH receptor (FSHR) mRNA in individual, well-characterized
preantral follicles. Method: Follicles were isolated from human ovarian
cortex obtained from either oophorectomies or cortical biopsies at
cesarean section. Expression of AR, FSHR, and AMHRII mRNA was determined
using a nested RT-PCR protocol. Results: AR mRNA was not detected
in any primordial follicles but was from the transitional stage onward.
The number of AR-positive follicles increased at each progressive
growth stage. The expression of AR preceded that of FSHR, and only
a small percentage of primary follicles expressed FSHR. AMHRII expression
was rarely detected. Conclusions: This is the first study to identify
the expression of AR in human transitional follicles. Results suggest
a role for androgens in promoting early follicle growth and challenging
the hypothesis that AMH exerts a direct, inhibitory effect on follicles
at this stage.},
url = {http://jcem.endojournals.org/cgi/content/abstract/92/3/1034}
}
@ARTICLE{Rice2011,
author = {Rice, Suman and Pellatt, Laura Jane and Bryan, Stacey Joanna and
Whitehead, Saffron Ann and Mason, Helen Diane},
title = {Action of Metformin on the Insulin-Signaling Pathway and on Glucose
Transport in Human Granulosa Cells},
journal = {J. Clin. Endocrinol. Metab.},
year = {2011},
volume = {96},
pages = {E427--435},
number = {3},
month = mar,
abstract = {ContextHyperinsulinemia in polycystic ovary syndrome is widely treated
with the insulin sensitizer metformin, which, in addition to its
systemic effects, directly affects the ovarian insulin-stimulated
steroidogenesis pathway. ObjectiveOur aim was to investigate the
interaction of metformin with the other insulin-stimulated ovarian
pathway, namely that leading to glucose uptake. DesignHuman granulosa-luteal
cells were cultured with metformin (10-7 M), insulin (10 ng/ml) or
metformin and insulin (met + ins) combined. Insulin receptor (IR)
involvement was assessed by culture with an (anti)-insulin receptor
(IR) antibody. Main outcome measuresThe effect of metformin on insulin-receptor
substrate proteins 1 and 2 (IRS-1 and -2) mRNA and protein expression
was determined. The KGN granulosa-cell line was used to investigate
the effect of insulin and metformin on Akt activation and glucose
transporter-4 (Glut-4) expression. Glut-4 translocation from the
cytosol to the membrane was determined in cytoplasmic and membrane-enriched
fractions of protein lysates. ResultsIRS-1 mRNA and protein increased
with all treatments. In contrast, basal IRS-2 mRNA levels were barely
detectable, but transcription was up-regulated by metformin. The
anti-IR antibody reduced treatment-stimulated IRS-1 to basal levels
and IRS-2 expression to an even greater extent than IRS-1, showing
greater dependence on the IR than IRS-1. Metformin in the presence
of insulin activated Akt and this was dependent on phosphoinositide-3
kinase, as was translocation of Glut-4 to the membrane. Metformin
was able to substantially enhance the insulin-stimulated translocation
of Glut-4 transporters from the cytosol to the membrane. ConclusionThis
net increase in Glut-4 transporters in the plasma membrane has the
potential to increase glucose uptake and metabolism by granulosa
cells of the insulin-resistant polycystic ovary, thereby facilitating
follicle growth.},
comment = {10.1210/jc.2010-2060},
url = {http://jcem.endojournals.org/cgi/content/abstract/96/3/E427}
}
@ARTICLE{Rich2005,
author = {Rich, Jeremy N. and Hans, Christopher and Jones, Beatrix and Iversen,
Edwin S. and McLendon, Roger E. and Rasheed, B.K. Ahmed and Dobra,
Adrian and Dressman, Holly K. and Bigner, Darell D. and Nevins, Joseph
R. and West, Mike},
title = {Gene Expression Profiling and Genetic Markers in Glioblastoma Survival},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {4051--4058},
number = {10},
month = may,
abstract = {Despite the strikingly grave prognosis for older patients with glioblastomas,
significant variability in patient outcome is experienced. To explore
the potential for developing improved prognostic capabilities based
on the elucidation of potential biological relationships, we did
analyses of genes commonly mutated, amplified, or deleted in glioblastomas
and DNA microarray gene expression data from tumors of glioblastoma
patients of age >50 for whom survival is known. No prognostic significance
was associated with genetic changes in epidermal growth factor receptor
(amplified in 17 of 41 patients), TP53 (mutated in 11 of 41 patients),
p16INK4A (deleted in 15 of 33 patients), or phosphatase and tensin
homologue (mutated in 15 of 41 patients). Statistical analysis of
the gene expression data in connection with survival involved exploration
of regression models on small subsets of genes, based on computational
search over multiple regression models with cross-validation to assess
predictive validity. The analysis generated a set of regression models
that, when weighted and combined according to posterior probabilities
implied by the statistical analysis, identify patterns in expression
of a small subset of genes that are associated with survival and
have value in assessing survival risks. The dominant genes across
such multiple regression models involve three key genes--SPARC (Osteonectin),
Doublecortex, and Semaphorin3B--which play key roles in cellular
migration processes. Additional analysis, based on statistical graphical
association models constructed using similar computational analysis
methods, reveals other genes which support the view that multiple
mediators of tumor invasion may be important prognostic factor in
glioblastomas in older patients.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/10/4051}
}
@ARTICLE{Richard2011,
author = {Richard, Carole and Ghibu, Steliana and Delemasure-Chalumeau, Stephanie
and Guilland, Jean-Claude and Des Rosiers, Christine and Zeller,
Marianne and Cottin, Yves and Rochette, Luc and Vergely, Catherine},
title = {Oxidative Stress and Myocardial Gene Alterations Associated with
Doxorubicin-Induced Cardiotoxicity in Rats Persist for 2 Months after
Treatment Cessation},
journal = {J. Pharmacol. Exp. Ther.},
year = {2011},
volume = {339},
pages = {807-814},
number = {3},
abstract = {The molecular mechanisms underlying doxorubicin (DOX)-induced cardiomyopathy
include alterations in cardiomyocytes' oxidative stress status and
in gene expression. Although such alterations have been reported
during in vivo DOX treatment of animals, it remains to be clarified
whether they persist after treatment cessation. To address this question,
rats were injected with either saline (1 ml/kg/day i.p; control)
or DOX (1 mg/kg/day i.p.) for 10 days, and 70 days later cardiac
functional parameters were evaluated in vivo by left ventricular
catheterization. Hearts were also harvested for histological analyses
as well as measurements of oxidative stress parameters by various
techniques and gene expression by quantitative polymerase chain reaction
of markers of cardiac pathological remodeling, namely atrial natriuretic
factor, myosin heavy chain {beta}, vascular endothelial growth factor
A (VEGF-A), and sarcoplasmic reticulum Ca+2 ATPase. Compared with
controls, DOX-treated rats displayed marked alterations in most parameters
even 2 months after cessation of treatment. These included 1) lower
left ventricular contractility (+dP/dt), 2) increased levels of plasma
and myocardial oxidative stress markers, namely thiobarbituric acid
reactive substances or dihydroethidium fluorescence, and 3) markedly
altered transcript levels for all measured markers of cardiac remodeling,
except VEGF-A. These changes correlated significantly with +dP/dt
values assessed in the two groups of animals. In conclusion, this
study demonstrated that as many as 2 months after cessation of DOX
treatment cardiac alterations persisted, reflecting increased oxidative
stress and pathological remodeling, the latter being linked to the
development of contractile dysfunction.},
doi = {10.1124/jpet.111.185892},
eprint = {http://jpet.aspetjournals.org/cgi/reprint/339/3/807.pdf},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/339/3/807}
}
@ARTICLE{Richard2007,
author = {Richard, E and Alvarez-Barrientos, A and Pérez, B and Desviat, LR
and Ugarte, M},
title = {Methylmalonic acidaemia leads to increased production of reactive
oxygen species and induction of apoptosis through the mitochondrial/caspase
pathway},
journal = {J. Pathol.},
year = {2007},
volume = {213},
pages = {453--461},
number = {4},
abstract = {Abstract 10.1002/path.2248.abs Methylmalonic acidaemia (MMA) is a
heterogeneous group of rare genetic metabolic disorders caused by
defects related to intracellular cobalamin (vitamin B12) metabolism.
Increasing evidence has emerged suggesting that free radical generation
is involved in the pathophysiology of neurodegenerative diseases,
including some inborn errors of metabolism. We have previously identified
in MMA patients several differentially expressed proteins involved
in oxidative stress [mitochondrial superoxide dismutase (MnSOD) and
mitochondrial glycerophosphate dehydrogenase (mGPDH)] and apoptosis
by a proteomic approach. We have now extensively evaluated various
parameters related to oxidative stress and apoptosis in cultured
fibroblasts from a spectrum of patients with methylmalonic acidaemia.
Fibroblasts from several MMA patients showed a significant increase
in intracellular reactive oxygen species (ROS) content and in MnSOD
expression level with respect to controls, suggesting a cellular
response to intrinsic ROS stress. Moreover, we have demonstrated,
using siRNA, that mGPDH is an important ROS generator in MMA patients.
Cells from patients with MMA had a higher rate of apoptosis than
those of controls and there was evidence that this process primarily
involves the mitochondrial/caspase-dependent pathway. ROS level–phenotype
correlation revealed that patients with severe neonatal cblB disorder
had elevated intracellular ROS content. These findings support the
possible role of oxidative stress in the pathophysiology of methylmalonic
acidaemia. Copyright © 2007 Pathological Society of Great Britain
and Ireland. Published by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {methylmalonic acidaemia, mitochondria, ROS, oxidative stress, apoptosis,
siRNA, flow cytometry},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2248}
}
@ARTICLE{Richard2011a,
author = {Richard, Jean-François and Roy, Monica and Audoy-Rémus, Julie and
Tremblay, Pierrot and Vallières, Luc},
title = {Crawling Phagocytes Recruited in the Brain Vasculature after Pertussis
Toxin Exposure through IL6, ICAM1 and ITGαM},
journal = {Brain Pathology},
year = {2011},
volume = {21},
pages = {661--671},
number = {6},
abstract = {The cerebral vasculature is constantly patrolled by rod-shaped leukocytes
crawling on the luminal endothelial surface. These cells are recruited
in greater numbers after exposure to bacterial lipopolysaccharide
(LPS) by a mechanism involving tumor necrosis factor (TNF), interleukin-1β
(IL1β) and angiopoietin-2 (Angpt2). Here, we report that the population
of crawling leukocytes, consisting mainly of granulocytes, is also
increased in the brains of mice suffering from experimental autoimmune
encephalomyelitis (EAE) or injected with pertussis toxin (PTX), which
is commonly used to induce EAE. However, this recruitment occurs
through an alternative mechanism, independent of Angpt2. In a series
of experiments using DNA microarrays, knockout mice and neutralizing
antibodies, we found that PTX acts indirectly on the endothelium
in part through IL6, which is essential for the post-transcriptional
upregulation of intercellular adhesion molecule 1 (ICAM1) in response
to PTX but not to LPS. We also found that phagocytes adhere to brain
capillaries through the interaction of integrin αM (ITGαM) with
ICAM1 and an unidentified ligand. In conclusion, this study supports
the concept that PTX promotes EAE, at least in part, by inducing
vascular changes necessary for the recruitment of patrolling leukocytes.},
doi = {10.1111/j.1750-3639.2011.00490.x},
issn = {1750-3639},
keywords = {blood vessels, cytokines, Mac1, myeloid cells, neuroinflammation,
polymorphonuclear cells},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2011.00490.x}
}
@ARTICLE{Richards2010,
author = {Richards, Mark P. and Proszkowiec-Weglarz, Monika and Rosebrough,
Robert W. and McMurtry, John P. and Angel, Roselina},
title = {Effects of early neonatal development and delayed feeding immediately
post-hatch on the hepatic lipogenic program in broiler chicks},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2010},
volume = {157},
pages = {374--388},
number = {4},
month = dec,
abstract = {The embryo to neonate transition is a critical period of development
that has significant impact on broiler production. During this time
important genetic programs governing metabolism and growth are established.
The goal of this work was to study the effects of early post-hatch
(PH) development and the time of initiation of feeding on activation
of the genetic program regulating hepatic lipogenesis. A comparison
of liver total RNA samples at hatch and 7 days PH was performed using
oligonucleotide-based (Affymetrix GeneChip®) chicken genome microarrays.
During the first week PH there was significant up-regulation of key
lipogenic genes including: ATP citrate lyase (ACL), malic enzyme
(ME), fatty acid synthase (FAS), acetyl-CoA carboxylase alpha (ACC[alpha]),
stearoyl-CoA desaturase-1 (SCD-1), sterol regulatory element binding
protein-2 (SREBP-2) and thyroid hormone responsive spot 14[alpha]
(Spot 14[alpha]) among others. These findings were confirmed using
gene-specific RT-PCR assays. In a follow-up study, we investigated
the effects of withholding feed for the first 48 h PH (delayed feeding,
DF) on lipogenic gene expression through 8 days PH. Body weight gain
was significantly depressed by DF. Plasma levels of the major metabolic
hormones that regulate lipogenic gene expression (insulin, glucagon
and T3) changed significantly during PH development, but were largely
unaffected by DF. Plasma glucose was significantly lower in the DF
group at 24 h PH but recovered thereafter. In general, DF inhibited
the up-regulation of lipogenic genes until feeding was initiated.
Delayed up-regulation was also observed for the lipogenic transcription
factor genes, SREBP-1, SREBP-2 and peroxisome proliferator-activated
receptor gamma (PPAR[gamma]), but not for carbohydrate response element
binding protein (ChREB) or liver X receptor (LXR). Our results offer
additional insight into the transcriptional programming of hepatic
lipogenesis in response to the transition from high fat (yolk) to
high carbohydrate (feed) nutrition that occurs during early PH development.},
issn = {1096-4959},
keywords = {Feeding, Lipogenesis, Lipid metabolism, Liver, Gene expression, Microarray,
Early post-hatch development, Broiler chicken},
url = {http://www.sciencedirect.com/science/article/B6T2R-50XS6NH-1/2/0e603d761636c47d9e0a5d18d031d75d}
}
@ARTICLE{Richards2006,
author = {Richards, Stephen M. and Jensen, Roderick V. and Liu, Meng and Sullivan,
Benjamin D. and Lombardi, Michael J. and Rowley, Patricia and Schirra,
Frank and Treister, Nathaniel S. and Suzuki, Tomo and Steagall, Rebecca
J. and Yamagami, Hiroko and Sullivan, David A.},
title = {Influence of sex on gene expression in the mouse lacrimal gland},
journal = {Experimental Eye Research},
year = {2006},
volume = {82},
pages = {13--23},
number = {1},
month = jan,
abstract = {Significant, sex-associated differences exist in the physiology and
pathophysiology of the lacrimal gland. We hypothesize that many of
these differences are due to fundamental variations in gene expression.
The purpose of this study was to determine the extent to which sex-related
differences in gene expression are present in the lacrimal gland.
Lacrimal glands were obtained from adult male and female BALB/c mice
(n=5-10 mice/sex/experiment), pooled according to sex and processed
for the isolation of RNA. Samples were analyzed for differentially
expressed mRNAs by using Atlas Mouse cDNA Expression Arrays, cDNA
amplification techniques, GEM 1 and 2 gene chips, CodeLink bioarrays
and quantitative real-time PCR (qPCR) procedures. Quantitative evaluation
of Atlas Array gene expression was performed with an image analysis
system developed in our laboratory, whereas gene chip data were analyzed
with Rosetta Resolver and GeneSifter.Net software. Statistical significance
was determined by using Student's t-test. Our results with CodeLink
bioarrays show that sex has a significant influence on the expression
of over 490 genes in the mouse lacrimal gland. These genes are involved
in a wide range of biological processes, molecular functions and
cellular components, including such activities as development, growth,
transcription, metabolism, signal transduction, transport, receptor
activity and protein and nucleic acid binding. The expression of
selected genes was confirmed by the use of GEM gene chips and qPCR.
Our findings also demonstrate that certain methodological approaches
are less useful in attempting to assess the magnitude of sex-associated
differences in the lacrimal gland. These results support our hypothesis
that sex-related differences in gene expression play a role in the
sexual dimorphism of the lacrimal gland.},
issn = {0014-4835},
keywords = {sex differences, gene expression, lacrimal gland, mouse, microarray},
url = {http://www.sciencedirect.com/science/article/B6WFD-4GG8W4W-3/2/73f4f999e099f38dbca261997161ccc5}
}
@ARTICLE{Richards2005,
author = {Richards, Stephen M. and Liu, Meng and Jensen, Roderick V. and Schirra,
Frank and Yamagami, Hiroko and Lombardi, Michael J. and Rowley, Patricia
and Treister, Nathaniel S. and Suzuki, Tomo and Sullivan, Benjamin
D. and Sullivan, David A.},
title = {Androgen regulation of gene expression in the mouse lacrimal gland},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2005},
volume = {96},
pages = {401--413},
number = {5},
month = sep,
abstract = {The objective of this study was to determine the nature and extent
of androgen influence on gene expression in the lacrimal gland. Lacrimal
glands were obtained from orchiectomized mice that had been treated
with testosterone or vehicle for 2 weeks, as well as from testicular
feminized mice and their Tabby controls. Samples were pooled according
to experiment, processed for the isolation of RNA, and analyzed for
differentially expressed mRNAs by using primarily CodeLink Bioarrays,
GEM 1 and 2 gene chips and quantitative real-time PCR (qPCR) procedures.
Gene chip data were analyzed with GeneSifter.Net software. Our results
demonstrate that testosterone regulates the expression of over 2000
genes in the lacrimal gland. Gene ontologies most affected by androgen
treatment included those related to cell growth, proliferation and
metabolism, cell communication and transport, nucleic acid binding,
signal transduction and receptor activities. Our findings also indicate
that androgen action may be mediated, at least in part, through classical
androgen receptors, and may contribute to the sex-related differences
in gene expression of lacrimal tissue. Overall, these results support
our working hypothesis that androgen action on the lacrimal gland
is mediated primarily through a receptor-associated regulation of
gene transcription.},
issn = {0960-0760},
keywords = {Testosterone, Sex differences, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T8X-4GKW738-1/2/9b69d4562b07af1a118a87b3809fc21f}
}
@ARTICLE{Richards2011,
author = {Richards, Thomas A. and Soanes, Darren M. and Jones, Meredith D.
M. and Vasieva, Olga and Leonard, Guy and Paszkiewicz, Konrad and
Foster, Peter G. and Hall, Neil and Talbot, Nicholas J.},
title = {Horizontal gene transfer facilitated the evolution of plant parasitic
mechanisms in the oomycetes},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {15258-15263},
number = {37},
abstract = {Horizontal gene transfer (HGT) can radically alter the genomes of
microorganisms, providing the capacity to adapt to new lifestyles,
environments, and hosts. However, the extent of HGT between eukaryotes
is unclear. Using whole-genome, gene-by-gene phylogenetic analysis
we demonstrate an extensive pattern of cross-kingdom HGT between
fungi and oomycetes. Comparative genomics, including the de novo
genome sequence of Hyphochytrium catenoides, a free-living sister
of the oomycetes, shows that these transfers largely converge within
the radiation of oomycetes that colonize plant tissues. The repertoire
of HGTs includes a large number of putatively secreted proteins;
for example, 7.6% of the secreted proteome of the sudden oak death
parasite Phytophthora ramorum has been acquired from fungi by HGT.
Transfers include gene products with the capacity to break down plant
cell walls and acquire sugars, nucleic acids, nitrogen, and phosphate
sources from the environment. Predicted HGTs also include proteins
implicated in resisting plant defense mechanisms and effector proteins
for attacking plant cells. These data are consistent with the hypothesis
that some oomycetes became successful plant parasites by multiple
acquisitions of genes from fungi.},
doi = {10.1073/pnas.1105100108},
eprint = {http://www.pnas.org/cgi/reprint/108/37/15258.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/37/15258}
}
@ARTICLE{Richardson2008,
author = {Richardson, Vicki M. and Staskal, Daniele F. and Ross, David G. and
Diliberto, Janet J. and DeVito, Michael J. and Birnbaum, Linda S.},
title = {Possible mechanisms of thyroid hormone disruption in mice by BDE
47, a major polybrominated diphenyl ether congener},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {226},
pages = {244--250},
number = {3},
month = feb,
abstract = {Polybrominated diphenyl ethers (PBDEs) are a class of polyhalogenated
aromatic compounds commercially used as fire retardants in consumer
products. These compounds have been shown to decrease thyroid hormone
concentrations in rodents after acute exposures. This study examines
the ability of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) to decrease
circulating thyroid hormone concentrations and pairs this with BDE
47-induced effects on genes involved in thyroid hormone homeostasis.
Female C57BL/6 mice (9 weeks old) were orally administered 3, 10,
or 100 mg/kg/day of BDE 47 for 4 days. Animals were euthanized 24 h
after the final dose (day 5) and liver, kidney, and serum were collected
for analysis. BDE 47 caused a significant 43% decrease at 100 mg/kg/day
in serum total thyroxine (T4) concentrations. There was no increase
in hepatic T4-glucuronidation activity, but significant increases
in hepatic Ugt1a1, Ugt1a7, and Ugt2b5 mRNA expression accompany significant
decreases in T4 concentrations at 100 mg/kg/day of BDE 47. Induction
of PROD activity occurred at the lowest dose (3 mg/kg/day). Cyp2b10
mRNA expression also increased significantly at 10 and 100 mg/kg/day.
These key findings show that BDE activates the nuclear receptor,
CAR. Decreases in Mdr1a mRNA expression also occurred at the lowest
dose administered (3 mg/kg/day BDE 47). BDE 47 exposure also decreased
hepatic transthyretin and monocarboxylate transporter 8 (Mct8) mRNA
expression, suggesting that while induction of UGTs may be partly
responsible for T4 decreases, other mechanisms are also involved.
No effects were seen in the kidney. We conclude that changes in hepatic
UGTs and transporters may be involved in decreases in circulating
T4 following BDE 47 exposure.},
issn = {0041-008X},
keywords = {BDE 47, Mice, Thyroid hormone, Cytochrome P450s, UGT, Transporters},
url = {http://www.sciencedirect.com/science/article/B6WXH-4PR3G7C-2/2/352e28be1aabf74d86b53e8d3f766697}
}
@ARTICLE{Richert2006,
author = {Richert, Lysiane and Liguori, Michael J. and Abadie, Catherine and
Heyd, Bruno and Mantion, Georges and Halkic, Nermin and Waring, Jeffrey
F.},
title = {Gene expression in human hepatocytes in suspension after isolation
is similar to the liver of origin, is not affected by hepatocyte
cold storage and cryopreservation, but is strongly changed after
hepatocyte plating},
journal = {Drug Metab. Dispos.},
year = {2006},
volume = {34},
pages = {870--879},
number = {5},
month = may,
abstract = {Isolated primary human hepatocytes are a well accepted system for
evaluating pharmacological and toxicological effects in humans. However,
questions remain regarding how culturing affects the liver-specific
functions of the hepatocytes. In addition, cryopreservation could
also potentially affect the differentiation state of the hepatocytes.
The first aim of the present study was to compare gene expression
in freshly isolated primary hepatocytes to that of the liver of origin
and to evaluate the expression changes occurring after cryopreservation/thawing,
both when maintained in suspension and after plating. The second
aim of the present study was to evaluate gene expression in hepatocytes
after cold storage of suspensions up to 24 h compared with freshly
isolated hepatocytes in suspension. Our results show that the gene
expression in freshly isolated human hepatocytes in suspension after
isolation is similar to that of the liver of origin. Furthermore,
gene expression in primary human hepatocytes in suspension is not
affected by hepatocyte cold storage and cryopreservation. However,
the gene expression is profoundly affected in monolayer cultures
after plating. Specifically, gene expression changes were observed
in cultured relative to suspensions of human hepatocytes that are
involved in cellular processes such as phase I/II metabolism, basolateral
and canalicular transport systems, fatty acid and lipid metabolism,
apoptosis, and proteasomal protein recycling. An oxidative stress
response may be partially involved in these changes in gene expression.
Taken together, these results may aid in the interpretation of data
collected from human hepatocyte experiments and suggest additional
utility for cold storage and cryopreservation of hepatocytes.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/34/5/870}
}
@ARTICLE{Richert2009,
author = {Richert, L. and Tuschl, G. and Abadie, C. and Blanchard, N. and Pekthong,
D. and Mantion, G. and Weber, J.-C. and Mueller, S.O.},
title = {Use of mRNA expression to detect the induction of drug metabolising
enzymes in rat and human hepatocytes},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {235},
pages = {86--96},
number = {1},
month = feb,
abstract = {It is important to investigate the induction of cytochrome P450 (CYP)
enzymes by drugs. The most relevant end point is enzyme activity;
however, this requires many cells and is low throughput. We have
compared the CYP1A, CYP2B and CYP3A induction response to eight inducers
in rat and human hepatocytes using enzyme activities (CYP1A2 (ethoxyresorufin),
2B (benzoxyresorufin for rat and bupropion for human) and CYP3A (testosterone))
and Taqman(TM) Low Density Array (TLDA) analysis. There was a good
correlation between the induction of CYP1A2, CYP2B6 and CYP3A4 enzyme
activities and mRNA expression in human hepatocytes. In contrast,
BROD activities and mRNA expression in rat hepatocytes correlated
poorly. However, bupropion hydroxylation correlated well with Cyp2b1
expression in rat hepatocytes. TLDA analysis of a panel of mRNAs
encoding for CYPs, phase 2 enzymes, nuclear receptors and transporters
revealed that the main genes induced by the 8 compounds tested were
the CYPs. AhR ligands also induced UDP-glucuronosyltransferases and
glutathione S-transferases in rat and human hepatocytes. The transporters,
MDR1, MDR3 and OATPA were the only transporter genes significantly
up-regulated in human hepatocytes. In rat hepatocytes Bsep, Mdr2,
Mrp2, Mrp3 and Oatp2 were up-regulated. We could then show a good
in vivo:in vitro correlation in the induction response of isolated
rat hepatocytes and ex-vivo hepatic microsomes for the drug development
candidate, EMD392949. In conclusion, application of TLDA methodology
to investigate the potential of compounds to induce enzymes in rat
and human hepatocytes increases the throughput and information gained
from one assay, without reducing the predictive capacity.},
issn = {0041-008X},
keywords = {Enzyme induction, mRNA expression, Rat hepatocytes, Human hepatocytes},
url = {http://www.sciencedirect.com/science/article/B6WXH-4V42J4G-1/2/cea0a50df4bf4524ac718f3905b7015c}
}
@ARTICLE{Richert2008,
author = {Richert, Lysiane and Tuschl, Gregor and Viollon-Abadie, Catherine
and Blanchard, Nadege and Bonet, Alexandre and Heyd, Bruno and Halkic,
Nermin and Wimmer, Elmar and Dolgos, Hugues and Mueller, Stefan O.},
title = {Species Differences in the Response of Liver Drug-Metabolizing Enzymes
to (S)-4-O-Tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric Acid
(EMD 392949) in Vivo and in Vitro},
journal = {Drug Metab. Dispos.},
year = {2008},
volume = {36},
pages = {702--714},
number = {4},
month = apr,
abstract = {Induction of drug-metabolizing enzymes (DMEs) is highly species-specific
and can lead to drug-drug interaction and toxicities. In this series
of studies we tested the species specificity of the antidiabetic
drug development candidate and mixed peroxisome proliferator-activated
receptor (PPAR) {alpha}/{gamma} agonist (S)-4-O-tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric
acid (EMD 392949, EMD) with regard to the induction of gene expression
and activities of DMEs, their regulators, and typical PPAR target
genes. EMD clearly induced PPAR{alpha} target genes in rats in vivo
and in rat hepatocytes but lacked significant induction of DMEs,
except for cytochrome P450 (P450) 4A. CYP2C and CYP3A were consistently
induced in livers of EMD-treated monkeys. Interestingly, classic
rodent peroxisomal proliferation markers were induced in monkeys
after 17 weeks but not after a 4-week treatment, a fact also observed
in human hepatocytes after 72 h but not 24 h of EMD treatment. In
human hepatocyte cultures, EMD showed similar gene expression profiles
and induction of P450 activities as in monkeys, indicating that the
monkey is predictive for human P450 induction by EMD. In addition,
EMD induced a similar gene expression pattern as the PPAR{alpha}
agonist fenofibrate in primary rat and human hepatocyte cultures.
In conclusion, these data showed an excellent correlation of in vivo
data on DME gene expression and activity levels with results generated
in hepatocyte monolayer cultures, enabling a solid estimation of
human P450 induction. This study also clearly highlighted major differences
between primates and rodents in the regulation of major inducible
P450s, with evidence of CYP3A and CYP2C inducibility by PPAR{alpha}
agonists in monkeys and humans.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/36/4/702}
}
@ARTICLE{Richey2007,
author = {Richey, Luke M. and George, Jonathan R. and Couch, Marion E. and
Kanapkey, Brian K. and Yin, Xiaoying and Cannon, Trinitia and Stewart,
Paul W. and Weissler, Mark C. and Shores, Carol G.},
title = {Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {6561--6567},
number = {22},
month = nov,
abstract = {Purpose: Cancer cachexia is a devastating and understudied illness
in patients with head and neck squamous cell carcinoma (HNSCC). The
primary objective was to identify clinical characteristics and serum
levels of cytokines and cachexia-related factors in patients with
HNSCC. The secondary objective was to detect the occurrence of cytokine
and cachexia-related factor gene expression in HNSCC tumors. Experimental
Design: For the primary objective, cross-sectional data were obtained
from prospectively recruited patients identified as cachexia cases
and matching cachexia-free controls. For the secondary objective,
a retrospective cohort design with matched controls was used. Results:
Clinical characteristics associated with cancer cachexia in HNSCC
were T4 status (P = 0.01), increased C-reactive protein (P = 0.01),
and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis
of serum cytokine levels found increased interleukin (IL)-6 (P =
0.04). A highly sensitive ELISA confirmed the multiplex result for
increased IL-6 in cachectic patients (P = 0.02). Quality of life
was substantially reduced in patients with cachexia compared with
noncachectic patients (P < 0.01). All tumors of HNSCC patients both
with and without cachexia expressed RNA for each cytokine tested
and the cachexia factor lipid-mobilizing factor. There were no statistically
significant differences between the cytokine and cachexia factor
RNA expression of cachectic and noncachectic patients (each P > 0.05).
No tumors expressed the cachexia factor proteolysis-inducing factor.
Conclusion: We have identified clinical characteristics and pathophysiologic
mechanisms associated with cancer cachexia in a carefully defined
population of patients with HNSCC. The data suggest that the acute-phase
response and elevated IL-6 are associated with this complex disease
state. We therefore hypothesize that IL-6 may represent an important
therapeutic target for HNSCC patients with cancer cachexia.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/22/6561}
}
@ARTICLE{Richter2010,
author = {Richter, Rene and Behringer, Carina and Muller, Isabel Karin and
Schwechheimer, Claus},
title = {The GATA-type transcription factors GNC and GNL/CGA1 repress gibberellin
signaling downstream from DELLA proteins and PHYTOCHROME-INTERACTING
FACTORS},
journal = {Genes \& Dev.},
year = {2010},
volume = {24},
pages = {2093--2104},
number = {18},
month = sep,
abstract = {The phytohormone gibberellin (GA) regulates various developmental
processes in plants such as germination, greening, elongation growth,
and flowering time. DELLA proteins, which are degraded in response
to GA, repress GA signaling by inhibitory interactions with PHYTOCHROME-INTERACTING
FACTOR (PIF) family transcription factors. How GA signaling is controlled
downstream from the DELLA and PIF regulators is, at present, unclear.
Here, we characterize GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM
INVOLVED) and GNL/CGA1 (GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR1),
two homologous GATA-type transcription factors from Arabidopsis thaliana
that we initially identified as GA-regulated genes. Our genetic analyses
of loss-of-function mutants and overexpression lines establish that
GNC and GNL are functionally redundant regulators of germination,
greening, elongation growth and flowering time. We further show by
chromatin immunoprecipitation that both genes are potentially direct
transcription targets of PIF transcription factors, and that their
expression is up-regulated in pif mutant backgrounds. In line with
a key role of GNC or GNL downstream from DELLA and PIF signaling,
we find that their overexpression leads to gene expression changes
that largely resemble those observed in a ga1 biosynthesis mutant
or a pif quadruple mutant. These findings, together with the fact
that gnc and gnl loss-of-function mutations suppress ga1 phenotypes,
support the hypothesis that GNC and GNL are important repressors
of GA signaling downstream from the DELLA and PIF regulators.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/24/18/2093}
}
@ARTICLE{Ricicova2003,
author = {Ricicova, Marketa and Palkova, Zdena},
title = {Comparative analyses of Saccharomyces cerevisiae RNAs using Agilent
RNA 6000 Nano Assay and agarose gel electrophoresis},
journal = {FEMS Yeast Research},
year = {2003},
volume = {4},
pages = {119--122},
number = {1},
abstract = {Abstract Precise quantification and quality characterisation of isolated
RNAs are prerequisites for their further exploitation in genome-wide
microarrays, Northern blots, cDNA library preparation and others.
Our data indicate that RNA analyses using Agilent RNA Nano Assay
exhibit several advantages when compared with those performed on
ethidium bromide-stained agarose gel electrophoresis or on a spectrophotometer.
The RNA Nano Assay makes it possible to estimate RNA concentrations
in the range from 1000 ng μl−1 to 17 ng μl−1. The presence
of impurities including traces of DNA within RNA samples does not
influence the concentration measurements. Like agarose gel electrophoresis,
RNA Nano Assay allows to analyse RNAs dissolved in formamide and
therefore protected against RNase action. Moreover, it allows a clearer
distinction of partially degraded samples. The limitation of RNA
Nano Assay is the impossibility to detect and to analyse double-stranded
RNAs.},
issn = {1567-1364},
keywords = {RNA analysis, Agilent Bioanalyzer RNA 6000 Nano Assay, Agarose electrophoresis,
Double-stranded RNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1016/S1567-1356(03)00145-4}
}
@ARTICLE{Ricicova2003a,
author = {Ricicová, Markéta and Palková, Zdena},
title = {Comparative analyses of Saccharomyces cerevisiae RNAs using Agilent
RNA 6000 Nano Assay and agarose gel electrophoresis},
journal = {FEMS Yeast Research},
year = {2003},
volume = {4},
pages = {119--122},
number = {1},
month = oct,
abstract = {Precise quantification and quality characterisation of isolated RNAs
are prerequisites for their further exploitation in genome-wide microarrays,
Northern blots, cDNA library preparation and others. Our data indicate
that RNA analyses using Agilent RNA Nano Assay exhibit several advantages
when compared with those performed on ethidium bromide-stained agarose
gel electrophoresis or on a spectrophotometer. The RNA Nano Assay
makes it possible to estimate RNA concentrations in the range from
1000 ng [mu]l-1 to 17 ng [mu]l-1. The presence of impurities including
traces of DNA within RNA samples does not influence the concentration
measurements. Like agarose gel electrophoresis, RNA Nano Assay allows
to analyse RNAs dissolved in formamide and therefore protected against
RNase action. Moreover, it allows a clearer distinction of partially
degraded samples. The limitation of RNA Nano Assay is the impossibility
to detect and to analyse double-stranded RNAs.},
issn = {1567-1356},
keywords = {RNA analysis, Agilent Bioanalyzer RNA 6000 Nano Assay, Agarose electrophoresis,
Double-stranded RNA},
url = {http://www.sciencedirect.com/science/article/B6W8C-48MYF50-1/2/83e1887e57cfa76a1aaf641bf0d20c7f}
}
@ARTICLE{Riddell2008,
author = {Riddell, David R. and Zhou, Hua and Atchison, Kevin and Warwick,
Helen K. and Atkinson, Peter J. and Jefferson, Julius and Xu, Lin
and Aschmies, Suzan and Kirksey, Yolanda and Hu, Yun and Wagner,
Erik and Parratt, Adrienne and Xu, Jane and Li, Zhuting and Zaleska,
Margaret M. and Jacobsen, J. Steve and Pangalos, Menelas N. and Reinhart,
Peter H.},
title = {Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {11445--11453},
number = {45},
month = nov,
abstract = {Inheritance of the apoE4 allele ({varepsilon}4) increases the risk
of developing Alzheimer's disease; however, the mechanisms underlying
this association remain elusive. Recent data suggest that inheritance
of {varepsilon}4 may lead to reduced apoE protein levels in the CNS.
We therefore examined apoE protein levels in the brains, CSF and
plasma of {varepsilon}2/2, {varepsilon}3/3, and {varepsilon}4/4 targeted
replacement mice. These apoE mice showed a genotype-dependent decrease
in apoE levels; {varepsilon}2/2 >{varepsilon}3/3 >{varepsilon}4/4.
Next, we sought to examine the relative contributions of apoE4 and
apoE3 in the {varepsilon}3/4 mouse brains. ApoE4 represented 30-40%
of the total apoE. Moreover, the absolute amount of apoE3 per allele
was similar between {varepsilon}3/3 and {varepsilon}3/4 mice, implying
that the reduced levels of total apoE in {varepsilon}3/4 mice can
be explained by the reduction in apoE4 levels. In culture medium
from {varepsilon}3/4 human astrocytoma or {varepsilon}3/3, {varepsilon}4/4
and {varepsilon}3/4 primary astrocytes, apoE4 levels were consistently
lower than apoE3. Secreted cholesterol levels were also lower from
{varepsilon}4/4 astrocytes. Pulse-chase experiments showed an enhanced
degradation and reduced half-life of newly synthesized apoE4 compared
with apoE3. Together, these data suggest that astrocytes preferentially
degrade apoE4, leading to reduced apoE4 secretion and ultimately
to reduced brain apoE levels. Moreover, the genotype-dependent decrease
in CNS apoE levels, mirror the relative risk of developing AD, and
suggest that low levels of total apoE exhibited by {varepsilon}4
carriers may directly contribute to the disease progression, perhaps
by reducing the capacity of apoE to promote synaptic repair and/or
A{beta} clearance.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/45/11445}
}
@ARTICLE{Riddell2007,
author = {Riddell, David R. and Zhou, Hua and Comery, Thomas A. and Kouranova,
Evguenia and Lo, C. Frederick and Warwick, Helen K. and Ring, Robert
H. and Kirksey, Yolanda and Aschmies, Suzan and Xu, Jane and Kubek,
Katie and Hirst, Warren D. and Gonzales, Catherine and Chen, Yi and
Murphy, Erin and Leonard, Sarah and Vasylyev, Dmytro and Oganesian,
Aram and Martone, Robert L. and Pangalos, Menelas N. and Reinhart,
Peter H. and Jacobsen, J. Steve},
title = {The LXR agonist TO901317 selectively lowers hippocampal A[beta]42
and improves memory in the Tg2576 mouse model of Alzheimer's disease},
journal = {Molecular and Cellular Neuroscience},
year = {2007},
volume = {34},
pages = {621--628},
number = {4},
month = apr,
abstract = {Recent studies show that intracellular cholesterol levels can modulate
the processing of amyloid precursor protein to A[beta] peptide. Moreover,
cholesterol-rich apoE-containing lipoproteins may also promote A[beta]
clearance. Agonists of the liver X receptor (LXR) transcriptionally
induce genes involved in intracellular lipid efflux and transport,
including apoE. Thus, LXR agonists have the potential to both inhibit
APP processing and promote A[beta] clearance. Here we show that LXR
agonist, TO901317, increased hippocampal ABCA1 and apoE and decreased
A[beta]42 levels in APP transgenic mice. TO901317 had no significant
effects on levels of A[beta]40, full length APP, or the APP processing
products. Next, we examined the effects of TO901317 in the contextual
fear conditioning paradigm; TO901317 completely reversed the contextual
memory deficit in these mice. These data demonstrate that LXR agonists
do not directly inhibit APP processing but rather facilitate the
clearance of A[beta]42 and may represent a novel therapeutic approach
to Alzheimer's disease.},
issn = {1044-7431},
url = {http://www.sciencedirect.com/science/article/B6WNB-4MWXPVV-6/2/ca493d5b7295da4b57374341f3d2a731}
}
@ARTICLE{Ridder2009,
author = {Ridder, Dirk A. and Bulashevska, Svetlana and Chaitanya, Ganta Vijay
and Babu, Phanithi Prakash and Brors, Benedikt and Eils, Roland and
Schneider, Armin and Schwaninger, Markus},
title = {Discovery of transcriptional programs in cerebral ischemia by in
silico promoter analysis},
journal = {Brain Research},
year = {2009},
volume = {1272},
pages = {3--13},
month = may,
abstract = {In stroke, gene transcription plays a central role in processes such
as neuroinflammation and neuroregeneration. To predict new transcriptional
regulatory mechanisms in cerebral ischemia, we applied a computational
approach combining two kinds of information: the results of a microarray
analysis in a mouse model of stroke and in silico detection of transcription
factor (TF) binding sites in promoter regions of the genes on the
array. By using a discriminative logistic regression model, we identified
binding sites significantly associated with the up-regulation of
genes. Out of 356 TF binding sites defined in TRANSFAC, we could
link 32 to gene up-regulation in cerebral ischemia. These sites bind
both TFs with an established and a so far unknown role in cerebral
ischemia. To evaluate the results further we investigated whether
two TFs, CCAAT/enhancer binding protein [beta] (C/EBP[beta]) and
vitamin D receptor (VDR), are activated as predicted. Immunohistochemistry
demonstrated that C/EBP[beta] and VDR translocated to the nucleus
in cerebral ischemia. Chromatin immunoprecipitation revealed increased
binding of C/EBP[beta] to the promoter of its target gene saa3. In
addition, we found evidence for the up-regulation of VDR in brain
samples from human stroke patients. These results confirm the activation
of C/EBP[beta] and VDR in cerebral ischemia. Thus, our in silico
analysis may provide additional information on transcriptional regulation
in stroke and suggests several novel transcriptional programs for
further exploration.},
issn = {0006-8993},
keywords = {Cerebral ischemia, Transcription, Vitamin D receptor, C/EBP[beta],
Promoter, Bioinformatics},
url = {http://www.sciencedirect.com/science/article/B6SYR-4VYP97X-3/2/8b4cc0c6e850b7d5415896caa1bb1ce6}
}
@ARTICLE{Rieck2009,
author = {Rieck, Sebastian and White, Peter and Schug, Jonathan and Fox, Alan
J. and Smirnova, Olga and Gao, Nan and Gupta, Rana K. and Wang, Zhao
V. and Scherer, Philipp E. and Keller, Mark P. and Attie, Alan D.
and Kaestner, Klaus H.},
title = {The Transcriptional Response of the Islet to Pregnancy in Mice},
journal = {Mol. Endocrinol.},
year = {2009},
volume = {23},
pages = {1702--1712},
number = {10},
month = oct,
abstract = {The inability of the {beta}-cell to meet the demand for insulin brought
about by insulin resistance leads to type 2 diabetes. In adults,
{beta}-cell replication is one of the mechanisms thought to cause
the expansion of {beta}-cell mass. Efforts to treat diabetes require
knowledge of the pathways that drive facultative {beta}-cell proliferation
in vivo. A robust physiological stimulus of {beta}-cell expansion
is pregnancy and identifying the mechanisms underlying this stimulus
may provide therapeutic leads for the treatment of type 2 diabetes.
The peak in {beta}-cell proliferation during pregnancy occurs on
d 14.5 of gestation in mice. Using advanced genomic approaches, we
globally characterize the gene expression signature of pancreatic
islets on d 14.5 of gestation during pregnancy. We identify a total
of 1907 genes as differentially expressed in the islet during pregnancy.
The islet's ability to compensate for relative insulin deficiency
during metabolic stress is associated with the induction of both
proliferative and survival pathways. A comparison of the genes induced
in three different models of islet expansion suggests that diverse
mechanisms can be recruited to expand islet mass. The identification
of many novel genes involved in islet expansion during pregnancy
provides an important resource for diabetes researchers to further
investigate how these factors contribute to the maintenance of not
only islet mass, but ultimately {beta}-cell mass.},
url = {http://mend.endojournals.org/cgi/content/abstract/23/10/1702}
}
@ARTICLE{Riedel2009,
author = {Riedel, Christian U. and Monk, Ian R. and Casey, Pat G. and Waidmann,
Mark S. and Gahan, Cormac G. M. and Hill, Colin},
title = {AgrD-dependent quorum sensing affects biofilm formation, invasion,
virulence and global gene expression profiles in Listeria monocytogenes},
journal = {Molecular Microbiology},
year = {2009},
volume = {71},
pages = {1177--1189},
number = {5},
abstract = {Summary The Listeria monocytogenes Agr peptide-sensing system has
been analysed by creating a deletion mutant in agrD, the structural
gene for the putative quorum-sensing peptide. The ΔagrD mutant displayed
significantly reduced biofilm formation, a defect which could be
restored by genetic or physical complementation. A reduced invasion
of Caco-2 intestinal epithelial cells was observed for the ΔagrD
mutant while phagocytosis by THP-1 macrophages was unaffected. Additionally,
the level of internalin A (InlA) in the cell wall was decreased in
the ΔagrD mutant. Expression profiling of virulence genes (hlyA,
actA, plcA, prfA and inlA) identified a finely tuned regulation which
resulted in an impaired virulence response in the ΔagrD mutant.
The mutant is also significantly attenuated for virulence in mice,
as revealed by bioluminescent in vivo imaging. On day 3 post infection,
systemic dissemination to livers and spleens had occurred for the
wild type, whereas the ΔagrD mutant remained localized to the liver.
Microarray analysis identified 126 and 670 genes as significantly
regulated in exponential and stationary phase respectively. The results
presented here suggest that peptide sensing plays an important role
in the biology of L. monocytogenes, with relevant phenotypes in
both the saprophytic and parasitic lifecycles.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2008.06589.x}
}
@ARTICLE{Riederer2011,
author = {Riederer, Allison and Takasuka, Taichi E. and Makino, Shin-ichi and
Stevenson, David M. and Bukhman, Yury V. and Elsen, Nathaniel L.
and Fox, Brian G.},
title = {Global Gene Expression Patterns in Clostridium thermocellum as Determined
by Microarray Analysis of Chemostat Cultures on Cellulose or Cellobiose},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {1243--1253},
number = {4},
month = feb,
abstract = {A microarray study of chemostat growth on insoluble cellulose or soluble
cellobiose has provided substantial new information on Clostridium
thermocellum gene expression. This is the first comprehensive examination
of gene expression in C. thermocellum under defined growth conditions.
Expression was detected from 2,846 of 3,189 genes, and regression
analysis revealed 348 genes whose changes in expression patterns
were growth rate and/or substrate dependent. Successfully modeled
genes included those for scaffoldin and cellulosomal enzymes, intracellular
metabolic enzymes, transcriptional regulators, sigma factors, signal
transducers, transporters, and hypothetical proteins. Unique genes
encoding glycolytic pathway and ethanol fermentation enzymes expressed
at high levels simultaneously with previously established maximal
ethanol production were also identified. Ranking of normalized expression
intensities revealed significant changes in transcriptional levels
of these genes. The pattern of expression of transcriptional regulators,
sigma factors, and signal transducers indicates that response to
growth rate is the dominant global mechanism used for control of
gene expression in C. thermocellum.},
comment = {10.1128/AEM.02008-10},
url = {http://aem.asm.org/cgi/content/abstract/77/4/1243}
}
@ARTICLE{Riedmaier2009,
author = {Riedmaier, Irmgard and Tichopad, Ales and Reiter, Martina and Pfaffl,
Michael W. and Meyer, Heinrich H.D.},
title = {Identification of potential gene expression biomarkers for the surveillance
of anabolic agents in bovine blood cells},
journal = {Analytica Chimica Acta},
year = {2009},
volume = {638},
pages = {106--113},
number = {1},
month = apr,
abstract = {In the EU, the use of anabolic steroids in food producing animals
has been forbidden since 1988. The routine methods used in practice
are based on the detection of hormonal residues. To overcome these
routine methods, growth-promoting agents are sometimes administered
at concentrations below the detection limit and new anabolic substances
are designed. Therefore, new monitoring systems are needed to overcome
the misuse of anabolic agents in meat production. In this study,
a new monitoring system was applied: the quantification of mRNA gene
expression changes by quantitative real time reverse transcription
polymerase chain reaction (qRT-PCR). Blood was selected as ideal
tissue for biomarker screening. From the literature, it is known
that steroid hormones affect mRNA gene expression of the different
blood cells, which can easily be taken from the living animal. In
an animal trial, 18 Nguni heifers were separated to two groups of
nine animals. One group served as untreated control and the other
group was treated with a combination of trenbolone acetate plus estradiol
for 39 days in order to allow the detection of the effect on mRNA
expression in blood at three time points. Candidate genes used for
developing a biomarker pattern were chosen by screening the actual
literature for anabolic effects on blood cells. It could be demonstrated
that the combination of trenbolone acetate plus estradiol significantly
influences mRNA expression of the steroid receptors (ER-[alpha] and
GR-[alpha]), the apotosis regulator Fas, the proinflammatory interleukins
IL-1[alpha], IL-1[beta] and IL-6 and of MHCII, CK, MTPN, RBM5 and
Actin-[beta]. Advanced statistical analysis by Principal Components
Analysis (PCA) indicated that these genes represent potential biomarkers
for this hormone combination in whole blood.},
issn = {0003-2670},
keywords = {Anabolic agents, Trenbolone acetate, Estradiol, Biomarker, Gene expression,
Quantitative real time reverse transcription polymerase chain reaction
(qRT-PCR), Principal components analysis},
url = {http://www.sciencedirect.com/science/article/B6TF4-4VNH42T-1/2/84ffc5fc3a3f1340e794ec01ea540306}
}
@ARTICLE{Riedmaier2009a,
author = {Riedmaier, Irmgard and Tichopad, Ales and Reiter, Martina and Pfaffl,
Michael W. and Meyer, Heinrich H.D.},
title = {Influence of testosterone and a novel SARM on gene expression in
whole blood of Macaca fascicularis},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2009},
volume = {114},
pages = {167--173},
number = {3-5},
month = apr,
abstract = {Anabolic hormones, including testosterone, have been suggested as
a therapy for aging-related conditions, such as osteoporosis and
sarcopenia. These therapies are sometimes associated with severe
androgenic side effects. A promising alternative to testosterone
replacement therapy are selective androgen receptor modulators (SARMs).
SARMs have the potential to mimic the desirable central and peripheral
androgenic anabolic effects of testosterone without having its side
effects. In this study we evaluated the effects of LGD2941, in comparison
to testosterone, on mRNA expression of selected target genes in whole
blood in an non-human model. The regulated genes can act as potential
blood biomarker candidates in future studies with AR ligands. Cynomolgus
monkeys (Macaca fascicularis) were treated either with testosterone
or LGD2941 for 90 days in order to compare their effects on mRNA
expression in blood. Blood samples were taken before SARM application,
on day 16 and on day 90 of treatment. Gene expression of 37 candidate
genes was measured using quantitative real-time RT-PCR (qRT-PCR)
technology. Our study shows that both testosterone and LGD2941 influence
mRNA expression of 6 selected genes out of 37 in whole blood. The
apoptosis regulators CD30L, Fas, TNFR1 and TNFR2 and the interleukins
IL-12B and IL-15 showed significant changes in gene expression between
control and the treatment groups and represent potential biomarkers
for androgen receptor ligands in whole blood.},
issn = {0960-0760},
keywords = {Testosterone, SARM, Biomarker, Gene expression, Real-time qRT-PCR},
url = {http://www.sciencedirect.com/science/article/B6T8X-4VJBTMT-5/2/7cfb285fb8066755815fd034a8243b5f}
}
@ARTICLE{Riegelhaupt2010,
author = {Riegelhaupt, Joshua J. and Waase, Marc P. and Garbarino, Jeanne and
Cruz, Daniel E. and Breslow, Jan L.},
title = {Targeted disruption of steroidogenic acute regulatory protein D4
leads to modest weight reduction and minor alterations in lipid metabolism},
journal = {J. Lipid Res.},
year = {2010},
volume = {51},
pages = {1134--1143},
number = {5},
month = may,
abstract = {Steroidogenic acute regulatory protein (StAR)D4 is a member of the
StAR related lipid transfer family. Homology comes from the [~]210
amino acid lipid binding domain implicated in intracellular transport,
cell signaling, and lipid metabolism. StARD4 was identified as a
gene downregulated 2-fold by dietary cholesterol (Soccio, R. E.,
R. M. Adams, K. N. Maxwell, and J. L. Breslow. 2005. Differential
gene regulation of StarD4 and StarD5 cholesterol transfer proteins.
Activation of StarD4 by sterol regulatory element-binding protein-2
and StarD5 by endoplasmic reticulum stress. J. Biol. Chem. 280: 19410-19418).
A mouse knockout was created to investigate StARD4's functionality
and role in lipid metabolism. Homozygous knockout mice exhibited
normal Mendelian mating genetics, but weighed less than wild-type
littermates, an effect not accounted for by energy metabolism or
food intake. Body composition as analyzed by DEXA scan showed no
significant difference. No significant alterations in plasma or liver
lipid content were observed on a chow diet, but female knockout mice
showed a decrease in gallbladder bile cholesterol and phospholipid
concentration. When challenged with a 0.2% lova{-}statin diet, StARD4
homozygous mice exhibited no changes. However, when challenged with
a 0.5% cholesterol diet, female StARD4 homozygous mice showed a moderate
decrease in total cholesterol, LDL, and cholesterol ester concentrations.
Microarray analysis of liver RNA found few changes. However, NPC1's
expression, a gene not on the microarray, was decreased [~]2.5-fold
in knockouts. These observations suggest that StARD4's role can largely
be compensated for by other intracellular cholesterol transporters.},
url = {http://www.jlr.org/cgi/content/abstract/51/5/1134}
}
@ARTICLE{Riehl2010,
author = {Riehl, Astrid and Bauer, Tobias and Brors, Benedikt and Busch, Hauke
and Mark, Regina and Németh, Julia and Gebhardt, Christoffer and
Bierhaus, Angelika and Nawroth, Peter and Eils, Roland and König,
Rainer and Angel, Peter and Hess, Jochen},
title = {Identification of the Rage-dependent gene regulatory network in a
mouse model of skin inflammation},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {537},
number = {1},
abstract = {BACKGROUND:In the past, molecular mechanisms that drive the initiation
of an inflammatory response have been studied intensively. However,
corresponding mechanisms that sustain the expression of inflammatory
response genes and hence contribute to the establishment of chronic
disorders remain poorly understood. Recently, we provided genetic
evidence that signaling via the receptor for advanced glycation end
products (Rage) drives the strength and maintenance of an inflammatory
reaction. In order to decipher the mode of Rage function on gene
transcription levels during inflammation, we applied global gene
expression profiling on time-resolved samples of mouse back skin,
which had been treated with the phorbol ester TPA, a potent inducer
of skin inflammation.RESULTS:Ranking of TPA-regulated genes according
to their time average mean and peak expression and superimposition
of data sets from wild-type (wt) and Rage-deficient mice revealed
that Rage signaling is not essential for initial changes in TPA-induced
transcription, but absolutely required for sustained alterations
in transcript levels. Next, we used a data set of differentially
expressed genes between TPA-treated wt and Rage-deficient skin and
performed computational analysis of their proximal promoter regions.
We found a highly significant enrichment for several transcription
factor binding sites (TFBS) leading to the prediction that corresponding
transcription factors, such as Sp1, Tcfap2, E2f, Myc and Egr, are
regulated by Rage signaling. Accordingly, we could confirm aberrant
expression and regulation of members of the E2f protein family in
epidermal keratinocytes of Rage-deficient mice.CONCLUSIONS:In summary,
our data support the model that engagement of Rage converts a transient
cellular stimulation into sustained cellular dysfunction and highlight
a novel role of the Rb-E2f pathway in Rage-dependent inflammation
during pathological conditions.},
doi = {10.1186/1471-2164-11-537},
issn = {1471-2164},
pubmedid = {20923549},
url = {http://www.biomedcentral.com/1471-2164/11/537}
}
@ARTICLE{Riehle2008,
author = {Riehle, Kimberly J. and Campbell, Jean S. and McMahan, Ryan S. and
Johnson, Melissa M. and Beyer, Richard P. and Bammler, Theo K. and
Fausto, Nelson},
title = {Regulation of liver regeneration and hepatocarcinogenesis by suppressor
of cytokine signaling 3},
journal = {J. Exp. Med.},
year = {2008},
volume = {205},
pages = {91--103},
number = {1},
month = jan,
abstract = {Suppressor of cytokine signaling 3 (SOCS3) down-regulates several
signaling pathways in multiple cell types, and previous data suggest
that SOCS3 may shut off cytokine activation at the early stages of
liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz,
A. Stephenson-Famy, M.E. Rosenfeld, G.M. Argast, P.C. Heinrich, and
N. Fausto. 2001.J. Clin. Invest. 107:1285-1292). We developed Socs3
hepatocyte-specific knockout (Socs3 h-KO) mice to directly study
the role of SOCS3 during liver regeneration after a two-thirds partial
hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement
of DNA replication and liver weight restoration after PH in comparison
with littermate controls. Without SOCS3, signal transducer and activator
of transcription 3 (STAT3) phosphorylation is prolonged, and activation
of the mitogenic extracellular signal-regulated kinase 1/2 (ERK1/2)
is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances
hepatocyte proliferation in association with enhanced STAT3 and ERK
activation after epidermal growth factor or interleukin 6 stimulation.
Microarray analyses show that SOCS3 modulates a distinct set of genes,
which fall into diverse physiological categories, after PH. Using
a model of chemical-induced carcinogenesis, we found that Socs3 h-KO
mice develop hepatocellular carcinoma at an accelerated rate. By
acting on cytokines and multiple proliferative pathways, SOCS3 modulates
both physiological and neoplastic proliferative processes in the
liver and may act as a tumor suppressor.},
url = {http://jem.rupress.org/cgi/content/abstract/205/1/91}
}
@ARTICLE{Riehle2010,
author = {Riehle, Ulrike and Mader, Andreas and Brandstetter, Thomas and Ruhe,
Jurgen and zur Hausen, Axel and Stickeler, Elmar},
title = {Nucleic acid sequence-based amplification in formalin-fixed and paraffin-embedded
breast-cancer tissues},
journal = {J. Clin. Pathol.},
year = {2010},
pages = {jcp.2010.078766--},
month = oct,
abstract = {AimTo evaluate the nucleic acid sequence-based amplification (NASBA)
technique to amplify mRNA isolated from formalin-fixed and paraffin-embedded
(FFPE) breast-cancer tissues. MethodsRNA was extracted from archived,
10-year-old FFPE tissues, and selected genes, namely ribosomal protein
S18 (RPS18), epidermal growth factor receptor 2 (HER2), estrogen
receptor alpha (ER{alpha}), Y box binding protein (YBX-1), matrix
metallopeptidase 11 (MMP11), caspase 8 (CASP8) and superoxide dismutase
2 (SOD2), were amplified by NASBA. ResultsDespite strong degradation
of the template, RNA amplification of all tested genes resulted in
strong hybridisation signals. Sensitivity tests showed that the RPS18
NASBA assay was more sensitive than real-time RT-PCR used as a reference
method. The sensitivity of the HER2, ER{alpha}, MMP11, YBX1, CASP8
and SOD2 NASBA assay was comparable with RT-PCR targeted to the respective
genes. ConclusionsThe results obtained indicate that NASBA is suitable
to amplify with high specificity and sensitivity, even strongly degraded
RNA isolated from FFPE tissues, and therefore can complement already-existing
amplification techniques such as RT-PCR for analysis of such tissues.},
url = {http://jcp.bmj.com/cgi/content/abstract/jcp.2010.078766v1}
}
@ARTICLE{Riesenberg2007,
author = {Riesenberg, Rainer and Weiler, Christoph and Spring, Oliver and Eder,
Martin and Buchner, Alexander and Popp, Tanja and Castro, Mirna and
Kammerer, Robert and Takikawa, Osamu and Hatz, Rudolf A. and Stief,
Christian G. and Hofstetter, Alfons and Zimmermann, Wolfgang},
title = {Expression of Indoleamine 2,3-Dioxygenase in Tumor Endothelial Cells
Correlates with Long-term Survival of Patients with Renal Cell Carcinoma},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {6993--7002},
number = {23},
month = dec,
abstract = {Purpose: The inflammatory enzyme indoleamine 2,3-dioxygenase (IDO)
participates in immune tolerance and tumor immune escape processes
by degradation of the essential amino acid tryptophan and formation
of toxic catabolites. Here, we analyzed the role of IDO in tumor
growth and disease progression in patients with clear cell renal
cell carcinoma (RCC). Experimental Design: Expression of IDO mRNA
was analyzed by quantitative reverse transcription-PCR in 55 primary
and 52 metastatic RCC, along with 32 normal kidneys. Western blot
and immunohistochemistry analyses were used to semiquantitatively
determine IDO proteins in a subset of tumor samples, in RCC cell
lines, and microvessel endothelial cells. IDO expression was correlated
with expression of the proliferation marker Ki67 in tumor cells and
survival of patients with tumor. Results: More than 75% of the clear
cell RCC in comparison to normal kidney contained elevated levels
of IDO mRNA, which correlated with their IDO protein content. Low
IDO mRNA levels in primary tumors represented an unfavorable independent
prognostic factor (hazard ratio, 3.8; P = 0.016). Unexpectedly, immunohistochemical
analyses revealed that IDO is nearly exclusively expressed in endothelial
cells of newly formed blood vessels and is virtually absent from
tumor cells, although RCC cells could principally synthesize IDO
as shown by in vitro stimulation with IFN-{gamma}. A highly significant
inverse correlation between the density of IDO-positive microvessels
and the content of proliferating Ki67-positive tumor cells in primary
and metastatic clear cell RCC was found (P = 0.004). Conclusions:
IDO in endothelial cells might limit the influx of tryptophan from
the blood to the tumor or generate tumor-toxic metabolites, thus
restricting tumor growth and contributing to survival.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/23/6993}
}
@ARTICLE{Riesgo2011,
author = {Riesgo, Ana And Pã‰rez-porro, Alicia R. And Carmona, Susana And Leys,
Sally P. And Giribet, Gonzalo},
title = {Optimization of preservation and storage time of sponge tissues to
obtain quality mRNA for next-generation sequencing},
journal = {Molecular Ecology Resources},
year = {2011},
pages = {no--no},
abstract = {Transcriptome sequencing with next-generation sequencing technologies
has the potential for addressing many long-standing questions about
the biology of sponges. Transcriptome sequence quality depends on
good cDNA libraries, which requires high-quality mRNA. Standard protocols
for preserving and isolating mRNA often require optimization for
unusual tissue types. Our aim was assessing the efficiency of two
preservation modes, (i) flash freezing with liquid nitrogen (LN2)
and (ii) immersion in RNAlater, for the recovery of high-quality
mRNA from sponge tissues. We also tested whether the long-term storage
of samples at −80 °C affects the quantity and quality of mRNA.
We extracted mRNA from nine sponge species and analysed the quantity
and quality (A260/230 and A260/280 ratios) of mRNA according to preservation
method, storage time, and taxonomy. The quantity and quality of mRNA
depended significantly on the preservation method used (LN2 outperforming
RNAlater), the sponge species, and the interaction between them.
When the preservation was analysed in combination with either storage
time or species, the quantity and A260/230 ratio were both significantly
higher for LN2-preserved samples. Interestingly, individual comparisons
for each preservation method over time indicated that both methods
performed equally efficiently during the first month, but RNAlater
lost efficiency in storage times longer than 2Â months compared with
flash-frozen samples. In summary, we find that for long-term preservation
of samples, flash freezing is the preferred method. If LN2 is not
available, RNAlater can be used, but mRNA extraction during the first
month of storage is advised.},
doi = {10.1111/j.1755-0998.2011.03097.x},
issn = {1755-0998},
keywords = {flash freezing, illumina, messenger RNA, nucleic acids, RNA isolation,
RNAlater},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-0998.2011.03097.x}
}
@ARTICLE{Riester2012,
author = {Riester, Anna and Issler, Orna and Spyroglou, Ariadni and Rodrig,
Sharon Haramati and Chen, Alon and Beuschlein, Felix},
title = {ACTH-Dependent Regulation of MicroRNA As Endogenous Modulators of
Glucocorticoid Receptor Expression in the Adrenal Gland},
journal = {Endocrinology},
year = {2012},
volume = {153},
pages = {212-222},
number = {1},
abstract = {MicroRNA (miR) are a subset of small RNA molecules, which posttranscriptionally
modulate target gene expression. Although miR have been demonstrated
to impact a number of processes during development and tumorigenesis,
little is known about the expression and the role of miR in the adrenal
gland. Because tight regulation of steroid synthesis is crucial for
maintaining homeostasis upon stressful stimuli, here, we determined
the miR expression pattern in mouse adrenal glands under baseline
conditions, as well as 10, 30, and 60 min upon ACTH stimulation,
using miR microarray. Changes in miR expression levels detected by
array analysis were confirmed by real-time PCR and further analyzed
by bioinformatic tools to identify miR that putatively target genes
involved in adrenal function. After selecting miR, with a significant
change in their expression level upon ACTH stimulation, four of the
predefined miR (miR-96, miR-101a, miR-142-3p, and miR-433) were found
to putatively target the glucocorticoid receptor [nuclear receptor
subfamily 3, group C, member 1 (Nr3c1)]. Nr3c1 expression levels
were elevated 10 min after ACTH stimulation but decreased after 60
min in comparison with baseline conditions. Modified Nr3c1-3'-untranslated
region constructs were further tested by in vitro luciferase assays.
Thereby, we could confirm that miR96, miR101a, miR142-3p, and miR433
target the Nr3c1-3'-untranslated region and result in a 20-40% repression
of it. Taken together, ACTH stimulation could be demonstrated to
acutely influence adrenal miR expression pattern in vivo; thus, potentially
modulating adrenal response to acute stressors.},
doi = {10.1210/en.2011-1285},
eprint = {http://endo.endojournals.org/cgi/reprint/153/1/212.pdf},
url = {http://endo.endojournals.org/cgi/content/abstract/153/1/212}
}
@ARTICLE{Rigault2011,
author = {Rigault, Philippe and Boyle, Brian and Lepage, Pierre and Cooke,
Janice E.K. and Bousquet, Jean and MacKay, John J.},
title = {A White Spruce Gene Catalog for Conifer Genome Analyses},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {14-28},
number = {1},
abstract = {Several angiosperm plant genomes, including Arabidopsis (Arabidopsis
thaliana), rice (Oryza sativa), poplar (Populus trichocarpa), and
grapevine (Vitis vinifera), have been sequenced, but the lack of
reference genomes in gymnosperm phyla reduces our understanding of
plant evolution and restricts the potential impacts of genomics research.
A gene catalog was developed for the conifer tree Picea glauca (white
spruce) through large-scale expressed sequence tag sequencing and
full-length cDNA sequencing to facilitate genome characterizations,
comparative genomics, and gene mapping. The resource incorporates
new and publicly available sequences into 27,720 cDNA clusters, 23,589
of which are represented by full-length insert cDNAs. Expressed sequence
tags, mate-pair cDNA clone analysis, and custom sequencing were integrated
through an iterative process to improve the accuracy of clustering
outcomes. The entire catalog spans 30 Mb of unique transcribed sequence.
We estimated that the P. glauca nuclear genome contains up to 32,520
transcribed genes owing to incomplete, partially sequenced, and unsampled
transcripts and that its transcriptome could span up to 47 Mb. These
estimates are in the same range as the Arabidopsis and rice transcriptomes.
Next-generation methods confirmed and enhanced the catalog by providing
deeper coverage for rare transcripts, by extending many incomplete
clusters, and by augmenting the overall transcriptome coverage to
38 Mb of unique sequence. Genomic sample sequencing at 8.5% of the
19.8-Gb P. glauca genome identified 1,495 clusters representing highly
repeated sequences among the cDNA clusters. With a conifer transcriptome
in full view, functional and protein domain annotations clearly highlighted
the divergences between conifers and angiosperms, likely reflecting
their respective evolutionary paths.},
doi = {10.1104/pp.111.179663},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/1/14.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/1/14}
}
@ARTICLE{Riggs2005,
author = {Riggs, Penny K. and Angel, Joe M. and Abel, Erika L. and DiGiovanni,
John},
title = {Differential gene expression in epidermis of mice sensitive and resistant
to phorbol ester skin tumor promotion},
journal = {Mol. Carcinog.},
year = {2005},
volume = {44},
pages = {122--136},
number = {2},
abstract = {Abstract 10.1002/mc.20127.abs Previous data from two-stage carcinogenesis
studies in mouse skin demonstrated that genetic control of susceptibility
to skin tumor promotion by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate
(TPA), in crosses between susceptible DBA/2J and resistant C57BL/6J
mice is a multigenic trait. Utilizing a cDNA microarray approach,
we compared global gene expression profiles in the epidermis of these
two mouse strains treated with TPA or vehicle (acetone). Gene expression
in the epidermis was analyzed after the treatment to identify global
effects of TPA, as well as potential candidate genes that modify
susceptibility to skin tumor promotion. DBA/2J and C57BL/6J mice
were treated topically four times with 3.4 nmol TPA or acetone over
a 2-wk period, and RNA was extracted from epidermis 6 h after the
final treatment. Labeled cDNA generated from each group was hybridized
to commercial cDNA microarrays (Agilent) containing more than 8000
targets. More than 450 genes were significantly influenced, directly
or indirectly, by TPA treatment in the epidermis of either strain.
Notably, 44 genes exhibited differential expression between the tumor
promotion sensitive and resistant mouse strains. Several genes that
were differentially expressed in DBA/2J versus C57BL/6J epidermis
after TPA treatment were located in chromosomal regions linked to
TPA promotion susceptibility. Three genes, Gsta4, Nmes1 (MGC58382),
and Serpinb2, located within promotion susceptibility loci Psl1 (chr
9), Psl2 (chr 2), and Psl3 (chr 1), respectively, were identified
in this analysis as potential candidates for modifiers of susceptibility
to skin tumor promotion by TPA. © 2005 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {carcinogenesis, promotion modifier genes, skin, 12-O-tetradecanoylphorbol-13-acetate},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20127}
}
@ARTICLE{Righetti2002,
author = {Righetti, Pier Giorgio and Gelfi, Cecilia and D'Acunto, Maria Rosa},
title = {Recent progress in DNA analysis by capillary electrophoresis},
journal = {ELECTROPHORESIS},
year = {2002},
volume = {23},
pages = {1361--1374},
number = {10},
abstract = {Abstract 10.1002/1522-2683(200205)23:10<1361::AID-ELPS1361>3.3.CO;2-A
A number of recent developments in DNA analysis by capillary electrophoresis
are here reviewed. They include capillary arrays for fast, parallel
DNA sequencing as well as microfabricated capillary arrays. Microfluidic
chips for DNA sizing and quantitation are also covered, as well as
microdevices containing arrays of regular obstacles acting as size-separators
during DNA migration. Screening of DNA point mutations by two much
improved techniques is also reported: in one case, such mutations
are detected (but only on relative short, ca. 60–70 base-long fragments)
by free electrophoresis in rather acidic (pH ca. 3) buffers; in the
case of single-strand chain polymorphism, an improved technique is
described based on near-neutral pH buffers with mixtures of Tris/MES
cations/zwitterions. When studying the behavior of inorganic and
organic cations in the Debye-Hückel layer of DNA, it was found that
the latter (especially a large number of Good’s buffers and other
zwitterions, such as His) would bind to the DNA filament not only
via charge interaction, but also via additional bonds, notably hydrogen
bonds, thus altering the electrophoretic (and possibly the biological)
behavior of DNA molecules. However, whether or not borate ions would
bind to DNA remains still an unsettled question. Finally, capillary
electrophoresis was found to be instrumental in measuring fine physicochemical
parameters pertaining to DNA polyelectrolytes, such as their free
mobility and their translational diffusion coefficients.},
issn = {1522-2683},
keywords = {DNA separations, DNA sequencing, Microchip devices, Point mutations,
Review},
publisher = {WILEY-VCH Verlag GmbH},
url = {http://dx.doi.org/10.1002/1522-2683(200205)23:10<1361::AID-ELPS1361>3.0.CO;2-J}
}
@ARTICLE{Righi2009,
author = {Righi, Valeria and Roda, Jose M. and Paz, José and Mucci, Adele
and Tugnoli, Vitaliano and Rodriguez-Tarduchy, Gemma and Barrios,
Laura and Schenetti, Luisa and Cerdán, Sebastián and GarcÃa-MartÃn,
MarÃa L.},
title = {1H HR-MAS and genomic analysis of human tumor biopsies discriminate
between high and low grade astrocytomas},
journal = {NMR Biomed.},
year = {2009},
volume = {22},
pages = {629--637},
number = {6},
abstract = {Abstract 10.1002/nbm.1377.abs We investigate the profile of choline
metabolites and the expression of the genes of the Kennedy pathway
in biopsies of human gliomas (n = 23) using 1H High Resolution
Magic Angle Spinning (HR-MAS, 11.7 Tesla, 277 K, 4000 Hz) and
individual genetic assays. 1H HR-MAS spectra allowed the resolution
and relative quantification by the LCModel of the resonances from
choline (Cho), phosphocholine (PC) and glycerophosphorylcholine (GPC),
the three main components of the combined tCho peak observed in gliomas
by in vivo1H NMR spectroscopy. All glioma biopsies depicted a prominent
tCho peak. However, the relative contributions of Cho, PC, and GPC
to tCho were different for low and high grade gliomas. Whereas GPC
is the main component in low grade gliomas, the high grade gliomas
show a dominant contribution of PC. This circumstance allowed the
discrimination of high and low grade gliomas by 1H HR-MAS, a result
that could not be obtained using the tCho/Cr ratio commonly used
by in vivo1H NMR spectroscopy. The expression of the genes involved
in choline metabolism has been investigated in the same biopsies.
High grade gliomas depict an upregulation of the β gene of choline
kinase and phospholipase C, as well as a downregulation of the cytidyltransferase
B gene, the balance of these being consistent with the accumulation
of PC. In the low grade gliomas, phospholipase A1 and lysophospholypase
are upregulated and phospholipase D is downregulated, supporting
the accumulation of GPC. The present findings offer a promising procedure
that will potentially help to accurately grade glioma tumors using
1H HR-MAS, providing in addition the genetic background for the alterations
of choline metabolism observed in high and low grade gliomas. Copyright
© 2009 John Wiley & Sons, Ltd.},
issn = {1099-1492},
keywords = {choline metabolism, tumors, HR-MAS, gliomas, genomics},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/nbm.1377}
}
@ARTICLE{Riis2010,
author = {Riis, Margit and Lüders, Torben and Nesbakken, Anne-Jorunn and Vollan,
Hilde and Kristensen, Vessela and Bukholm, Ida},
title = {Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker
in patients with breast cancer},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {686},
number = {1},
abstract = {BACKGROUND:Polycomb Group (PcG) proteins are epigenetic silencers
involved in maintaining cellular identity, and their deregulation
can result in cancer. Expression of Mel-18 and Bmi-1 has been studied
in tumor tissue, but not in adjacent non-cancerous breast epithelium.
Our study compares the expression of the two genes in normal breast
epithelium of cancer patients and relates it to the level of expression
in the corresponding tumors as well as in breast epithelium of healthy
women.METHODS:A total of 79 tumors, of which 71 malignant tumors
of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared
to the reduction mammoplastic specimens of 11 healthy women. In addition
there was available adjacent cancer free tissue for 23 of the malignant
tumors. The tissue samples were stored in RNAlater, RNA was isolated
to create expression microarray profile. These two genes were then
studied more closely first on mRNA transcription level by microarrays
(Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein
expression level using immunohistochemistry.RESULTS:Bmi-1 mRNA is
significantly up-regulated in adjacent normal breast tissue in breast
cancer patients compared to normal breast tissue from noncancerous
patients. Conversely, mRNA transcription level of Mel-18 is lower
in normal breast from patients operated for breast cancer compared
to breast tissue from mammoplasty. When protein expression of these
two genes was evaluated, we observed that most of the epithelial
cells were positive for Bmi-1 in both groups of tissue samples, although
the expression intensity was stronger in normal tissue from cancer
patients compared to mammoplasty tissue samples. Protein expression
of Mel-18 showed inversely stronger intensity in tissue samples from
mammoplasty compared to normal breast tissue from patients operated
for breast cancer.CONCLUSION:Bmi-1 mRNA level is consistently increased
and Mel-18 mRNA level is consistently decreased in adjacent normal
breast tissue of cancer patients as compared to normal breast tissue
in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can
be potentially used as a tool for stratifying women at risk of developing
malignancy.},
doi = {10.1186/1471-2407-10-686},
issn = {1471-2407},
pubmedid = {21162745},
url = {http://www.biomedcentral.com/1471-2407/10/686}
}
@ARTICLE{Rijn2011,
author = {Sarah J. van Rijn and Lies Gremeaux and Frank M. Riemers and Bas
Brinkhof and Hugo Vankelecom and Louis C. Penning and Björn P. Meij},
title = {Identification and characterisation of side population cells in the
canine pituitary gland},
journal = {The Veterinary Journal},
year = {2011},
pages = { - },
number = {0},
abstract = {To date, stem/progenitor cells have not been identified in the canine
pituitary gland. Cells that efficiently exclude the vital dye Hoechst
33342 can be visualised and identified using fluorescence activated
cell sorting (FACS) as a ‘side population’ (SP), distinct from
the main population (MP). Such SPs have been identified in several
tissues and display stem/progenitor cell characteristics. In this
study, a small SP (1.3%, n = 6) was detected in the anterior
pituitary glands of healthy dogs. Quantitative PCR indicated significantly
higher expression of CD34 and Thy1 in this SP, but no differences
in the expression of CD133, Bmi-1, Axin2 or Shh. Pro-opiomelanocortin
(POMC) and Lhx3 expression were significantly higher in the MP than
in the SP, but no differences in the expression of Tpit, GH or PRL
were found. The study demonstrated the existence of an SP of cells
in the normal canine pituitary gland, encompassing cells with stem
cell characteristics and without POMC expression.},
doi = {10.1016/j.tvjl.2011.06.030},
issn = {1090-0233},
keywords = {Dog},
url = {http://www.sciencedirect.com/science/article/pii/S1090023311002449}
}
@ARTICLE{Riker2008,
author = {Riker, Adam and Enkemann, Steven and Fodstad, Oystein and Liu, Suhu
and Ren, Suping and Morris, Christopher and Xi, Yaguang and Howell,
Paul and Metge, Brandon and Samant, Rajeev and Shevde, Lalita and
Li, Wenbin and Eschrich, Steven and Daud, Adil and Ju, Jingfang and
Matta, Jaime},
title = {The gene expression profiles of primary and metastatic melanoma yields
a transition point of tumor progression and metastasis},
journal = {BMC Medical Genomics},
year = {2008},
volume = {1},
pages = {13},
number = {1},
abstract = {BACKGROUND:The process of malignant transformation, progression and
metastasis of melanoma is poorly understood. Gene expression profiling
of human cancer has allowed for a unique insight into the genes that
are involved in these processes. Thus, we have attempted to utilize
this approach through the analysis of a series of primary, non-metastatic
cutaneous tumors and metastatic melanoma samples.METHODS:We have
utilized gene microarray analysis and a variety of molecular techniques
to compare 40 metastatic melanoma (MM) samples, composed of 22 bulky,
macroscopic (replaced) lymph node metastases, 16 subcutaneous and
2 distant metastases (adrenal and brain), to 42 primary cutaneous
cancers, comprised of 16 melanoma, 11 squamous cell, 15 basal cell
skin cancers. A Human Genome U133 Plus 2.0 array from Affymetrix,
Inc. was utilized for each sample. A variety of statistical software,
including the Affymetrix MAS 5.0 analysis software, was utilized
to compare primary cancers to metastatic melanomas. Separate analyses
were performed to directly compare only primary melanoma to metastatic
melanoma samples. The expression levels of putative oncogenes and
tumor suppressor genes were analyzed by semi- and real-time quantitative
RT-PCR (qPCR) and Western blot analysis was performed on select genes.RESULTS:We
find that primary basal cell carcinomas, squamous cell carcinomas
and thin melanomas express dramatically higher levels of many genes,
including SPRR1A/B, KRT16/17, CD24, LOR, GATA3, MUC15, and TMPRSS4,
than metastatic melanoma. In contrast, the metastatic melanomas express
higher levels of genes such as MAGE, GPR19, BCL2A1, MMP14, SOX5,
BUB1, RGS20, and more. The transition from non-metastatic expression
levels to metastatic expression levels occurs as melanoma tumors
thicken. We further evaluated primary melanomas of varying Breslow's
tumor thickness to determine that the transition in expression occurs
at different thicknesses for different genes suggesting that the
"transition zone" represents a critical time for the emergence of
the metastatic phenotype. Several putative tumor oncogenes (SPP-1,
MITF, CITED-1, GDF-15, c-Met, HOX loci) and suppressor genes (PITX-1,
CST-6, PDGFRL, DSC-3, POU2F3, CLCA2, ST7L), were identified and validated
by quantitative PCR as changing expression during this transition
period. These are strong candidates for genes involved in the progression
or suppression of the metastatic phenotype.CONCLUSION:The gene expression
profiling of primary, non-metastatic cutaneous tumors and metastatic
melanoma has resulted in the identification of several genes that
may be centrally involved in the progression and metastatic potential
of melanoma. This has very important implications as we continue
to develop an improved understanding of the metastatic process, allowing
us to identify specific genes for prognostic markers and possibly
for targeted therapeutic approaches.},
doi = {10.1186/1755-8794-1-13},
issn = {1755-8794},
pubmedid = {18442402},
url = {http://www.biomedcentral.com/1755-8794/1/13}
}
@ARTICLE{Rimbault2009,
author = {Rimbault, Maud and Robin, Stéphanie and Vaysse, Amaury and Galibert,
Francis},
title = {RNA profiles of rat olfactory epithelia: individual and age related
variations},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {572},
number = {1},
abstract = {BACKGROUND:Mammalian genomes contain a large number (~1000) of olfactory
receptor (OR) genes, many of which (20 to 50%) are pseudogenes. OR
gene transcription is not restricted to the olfactory epithelium,
but is found in numerous tissues. Using microarray hybridization
and RTqPCR, we analyzed the mRNA profiles of the olfactory epithelium
of male and female Brown Norway rats of different origins and ages
(newborn, adult and old).RESULTS:(1) We observed very little difference
between males and females and between rats from two different suppliers.
(2) Different OR genes were expressed at varying levels, rather than
uniformly across the four endoturbinates. (3) A large proportion
of the gene transcripts (2/3 of all probes) were detected in all
three age groups. Adult and older rats expressed similar numbers
of OR genes, both expressing more OR genes than newborns. (4) Comparisons
of whole transcriptomes or transcription profiles of expressed OR
genes only showed a clear clustering of the samples as a function
of age. (5) Most OR genes were expressed at lower levels at birth
than in older animals, but a small number of OR genes were expressed
specifically or were overexpressed in newborns.CONCLUSION:Not all
OR genes are expressed at a detectable level. Pups expressed fewer
OR genes than adult rats, and generally at a lower level; however,
a small subset of OR genes were more strongly expressed in these
newborn rats. The reasons for these differences are not understood.
However, the specific expression of some OR genes in newborn olfactory
epithelia may be related to the blindness and deafness of pups at
birth, when these pups are heavily reliant on olfaction and their
mother.},
doi = {10.1186/1471-2164-10-572},
issn = {1471-2164},
pubmedid = {19954510},
url = {http://www.biomedcentral.com/1471-2164/10/572}
}
@ARTICLE{RIMONDINI2002,
author = {RIMONDINI, ROBERTO and ARLINDE, CHRISTINA and SOMMER, WOLFGANG and
HEILIG, MARKUS},
title = {Long-lasting increase in voluntary ethanol consumption and transcriptional
regulation in the rat brain after intermittent exposure to alcohol},
journal = {FASEB J},
year = {2002},
volume = {16},
pages = {27--35},
number = {1},
month = jan,
abstract = {Prolonged exposure of the brain to ethanol is a prerequisite for developing
ethanol dependence, but the underlying neural adaptations are unknown.
Here we demonstrate that rats subjected to repeated cycles of intoxication
and withdrawal develop a marked and long-lasting increase in voluntary
ethanol intake. Exposure-induced but not spontaneous alcohol intake
is antagonized by acamprosate, a compound clinically effective in
human alcoholism. Expression analysis of cingulate cortex and amygdala
reveals a set of long-term up-regulated transcripts in this model.
These include members of pathways previously implicated in alcohol
dependence (glutamatergic, endocannabinoid, and monoaminergic neurotransmission),
as well as pathways not previously thought to be involved in this
disorder (e.g., members of the mitogen-activated protein kinase pathway).
Thus, alternating periods of ethanol intoxication and withdrawal
are sufficient to induce an altered functional brain state, which
is likely to be encoded by long-term changes in gene expression.
These observations may have important implications for how alcoholism
is managed clinically. Novel clinically effective treatments may
be possible to develop by targeting the products of genes found to
be regulated in our model.--Rimondini, R., Arlinde, C., Sommer, W.,
Heilig, M. Long-lasting increase in voluntary ethanol consumption
and transcriptional regulation in the rat brain after intermittent
exposure to alcohol.},
url = {http://www.fasebj.org/cgi/content/abstract/16/1/27}
}
@ARTICLE{Rinaldi2006,
author = {Rinaldi, Andrea and Kwee, Ivo and Taborelli, Monica and Largo, Cristina
and Uccella, Silvia and Martin, Vittoria and Poretti, Giulia and
Gaidano, Gianluca and Calabrese, Giuseppe and Martinelli, Giovanni
and Baldini, Luca and Pruneri, Giancarlo and Capella, Carlo and Zucca,
Emanuele and Cotter, Finbarr E. and Cigudosa, Juan C. and Catapano,
Carlo V. and Tibiletti, Maria G. and Bertoni, Francesco},
title = {Genomic and expression profiling identifies the B-cell associated
tyrosine kinase Syk as a possible therapeutic target in mantle cell
lymphoma},
journal = {British Journal of Haematology},
year = {2006},
volume = {132},
pages = {303--316},
number = {3},
abstract = {Summary Among B-cell lymphomas mantle cell lymphoma (MCL) has the
worst prognosis. By using a combination of genomic and expression
profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set),
we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis
and that could represent new therapeutic targets. Recurrent genomic
deletions and gains were detected. Genes were identified as overexpressed
in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including
the cancer genes BCL2 and MYC. Among the transcripts with high correlation
between DNA and RNA, we identified SYK, a tyrosine kinase involved
in B-cell receptor signalling. SYK was amplified at DNA level, as
validated by fluorescence in situ hybridisation (FISH) analysis,
and overexpressed at both RNA and protein levels in the JeKo-1 cell
line. Low-level amplification, with protein overexpression of Syk
was demonstrated by FISH in a small subset of clinical samples. After
treatment with low doses of the Syk inhibitor piceatannol, cell proliferation
arrest and apoptosis were induced in the cell line overexpressing
Syk, while cells expressing low levels of Syk were much less sensitive.
A combination of genomic and expression profiling suggested Syk inhibition
as a new therapeutic strategy to be explored in lymphomas.},
issn = {1365-2141},
keywords = {piceatannol, Affymetrix, isochromosome, 9q, Syk},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2005.05883.x}
}
@ARTICLE{Rinaudo2004,
author = {Rinaudo, Paolo and Schultz, Richard M},
title = {Effects of embryo culture on global pattern of gene expression in
preimplantation mouse embryos},
journal = {Reproduction},
year = {2004},
volume = {128},
pages = {301--311},
number = {3},
month = sep,
abstract = {Culture of preimplantation embryos affects gene expression. The magnitude
of the effect on the global pattern of gene expression, however,
is not known. We compared global patterns of gene expression in blastocysts
cultured from the one-cell stage in either Whitten's medium or KSOM
+ amino acids (KSOM/AA) with that of blastocysts that developed in
vivo, using the Affymetrix MOE430A chip. The analysis revealed that
expression of 114 genes was affected after culture in Whitten's medium,
whereas only 29 genes were mis-expressed after culture in KSOM/AA.
Expression Analysis Systematic Explorer was used to identify biological
and molecular processes that are perturbed after culture and indicated
that genes involved in protein synthesis, cell proliferation and
transporter function were down-regulated after culture in Whitten's
medium. A common set of genes involved in transporter function was
also down-regulated after culture in KSOM/AA. These results provide
insights as to why embryos develop better in KSOM/AA than in Whitten's
medium, and highlight the power of microarray analysis to assess
global patterns of gene expression.},
url = {http://www.reproduction-online.org/cgi/content/abstract/128/3/301}
}
@ARTICLE{Rinaudo2006,
author = {Rinaudo, Paolo F. and Giritharan, Gnanaratnam and Talbi, Said and
Dobson, Anthony T. and Schultz, Richard M.},
title = {Effects of oxygen tension on gene expression in preimplantation mouse
embryos},
journal = {Fertility and Sterility},
year = {2006},
volume = {86},
pages = {1265.e1--1265.e36},
number = {4, Supplement 1},
month = oct,
abstract = {Objective To compare the effects of atmospheric and physiologic oxygen
concentrations on the global patterns of gene expression during mouse
preimplantation development.Design Comparative analysis of in vivo-produced
and in vitro-produced embryos.Setting Research laboratory.Patient(s)
None.Intervention(s) Control embryos at the blastocyst stage that
developed in vivo were collected from uteri. Experimental embryos
were obtained at the zygote stage and cultured to the blastocyst
stage in Whitten's medium or KSOM medium with amino acids under 20%
oxygen (atmospheric) or 5% oxygen (physiologic).Main Outcome Measure(s)
Embryo development, cell number, and gene expression assayed by microarray
technology.Result(s) Low (physiologic) oxygen concentration is associated
with faster embryo development and increased cell number. In addition,
there are marked perturbations in the global pattern of gene expression,
as assessed by oligonucleotide microarray, after culture in 20% oxygen
as compared with 5% oxygen.Conclusion(s) Culture in low oxygen is
associated with fewer perturbations in the global pattern of gene
expression and more closely resembles that of the in vivo control
embryos. These findings provide rationale for culturing human embryos
in the presence of 5%, rather than 20%, oxygen.},
issn = {0015-0282},
keywords = {Microarray, gene expression, culture media, blastocyst, IVF, oxygen},
url = {http://www.sciencedirect.com/science/article/B6T6K-4M060X1-3/2/a8dbb806d0504c5d6f54469c6916308c}
}
@ARTICLE{Rinella2006,
author = {Rinella, Erica S. and Eversley, Chevonne D. and Carroll, Ian M. and
Andrus, Jason M. and Threadgill, David W. and Threadgill, Deborah
S.},
title = {Human epithelial-specific response to pathogenic Campylobacter jejuni},
journal = {FEMS Microbiology Letters},
year = {2006},
volume = {262},
pages = {236--243},
number = {2},
abstract = {Abstract The gastrointestinal epithelia of mammals are tolerant of
their resident gut microbiota but are usually highly responsive to
entero-pathogens; the host-specific responses have not been well
characterized. To this end, the transcriptional responses of cultured
human (Caco-2) and murine (CT-26) colonic epithelial cells were compared
after exposure with the microfloral bacterium Lactobacillus reuteri
or the human gastrointestinal pathogen Campylobacter jejuni. When
in bacterial broth, both species elicit a stronger differential gene
expression response in human colonic cells compared with mouse colonic
cells. However, when these data are adjusted to remove bacterial
broth effects, only human colonic epithelia exposed to C. jejuni
show altered gene expression, suggesting that the human pathogen
C. jejuni induces a host-specific response. The genes with altered
expression are involved in growth, transcription, and steroid biosynthesis.
Interestingly, human genes involved in cell polarity and water transport
were significantly changed in response to C. jejuni exposure, linking
infection with gastrointestinal disease. This study demonstrates
that mouse and human colonic epithelia remain relatively unresponsive
to commensal bacterial challenge, while the human pathogen C. jejuni
elicits a host-specific response.},
issn = {1574-6968},
keywords = {Campylobacter jejuni, Lactobacillus reuteri, intestinal epithelial
cells},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2006.00396.x}
}
@ARTICLE{Ring2006,
author = {Ring, Robert H. and Alder, Janet and Fennell, Myles and Kouranova,
Evguenia and Black, Ira B. and Thakker-Varia, Smita},
title = {Transcriptional profiling of brain-derived-neurotrophic factor-induced
neuronal plasticity: A novel role for nociceptin in hippocampal neurite
outgrowth},
journal = {J. Neurobiol.},
year = {2006},
volume = {66},
pages = {361--377},
number = {4},
abstract = {Abstract 10.1002/neu.20223.abs Brain derived neurotrophic factor (BDNF)
exhibits a sequence of actions on neurons ranging from acute enhancement
of transmission to long-term promotion of neurite outgrowth and synaptogenesis
associated with learning and memory. The manifold effects of BDNF
on neuronal modifications may be mediated by genomic alterations.
We previously found that BDNF treatment acutely increases transcription
of the synaptic vesicle protein Rab3A, required for trophin-induced
synaptic plasticity, as well as the peptide VGF, which increases
during learning. To elucidate comprehensive transcriptional programs
associated with short- and long-term BDNF exposure, we now examine
mRNA abundance and complexity using Affymetrix GeneChips in cultured
hippocampal neurons. Consistent with the modulation of synaptic plasticity,
BDNF treatment (3–6 h) induced mRNAs encoding the synapse-associated
proteins synaptojanin 2, neuronal pentraxin 1, septin 9, and ryanodine
receptor 2. BDNF also induced expression of mRNAs encoding neuropeptides
(6–12 h), including prepronociceptin, neuropeptide Y, and secretogranin.
To determine whether these neuropeptides induced by BDNF mediate
neuronal development, we examined their effects on hippocampal neurons.
The four mature peptides derived from post-translational processing
of the ppNociceptin propeptide induced the expression of several
immediate early genes in hippocampal cultures, indicating neuronal
activation. To examine the significance of activation, the effects
of nociceptin (orphanin FQ) and nocistatin on neurite outgrowth were
examined. Quantitative morphometric analysis revealed that nociceptin
significantly increased both average neurite length and average number
of neurites per neuron, while nocistatin had no effect on these parameters.
These results reveal a novel role for nociceptin and suggest that
these neuropeptide systems may contribute to the regulation of neuronal
function by BDNF. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006},
issn = {1097-4695},
keywords = {BDNF, nociceptin, neurite outgrowth, microarray, synaptic plasticity},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/neu.20223}
}
@ARTICLE{Ringhoff2009,
author = {Ringhoff, Danielle and Cassimeris, Lynne},
title = {Gene expression profiles in mouse embryo fibroblasts lacking stathmin,
a microtubule regulatory protein, reveal changes in the expression
of genes contributing to cell motility},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {343},
number = {1},
abstract = {BACKGROUND:Stathmin (STMN1) protein functions to regulate assembly
of the microtubule cytoskeleton by destabilizing microtubule polymers.
Stathmin over-expression has been correlated with cancer stage progression,
while stathmin depletion leads to death of some cancer cell lines
in culture. In contrast, stathmin-null mice are viable with minor
axonopathies and loss of innate fear response. Several stathmin binding
partners, in addition to tubulin, have been shown to affect cell
motility in culture. To expand our understanding of stathmin function
in normal cells, we compared gene expression profiles, measured by
microarray and qRT-PCR, of mouse embryo fibroblasts isolated from
STMN1+/+ and STMN1-/- mice to determine the transcriptome level changes
present in the genetic knock-out of stathmin.RESULTS:Microarray analysis
of STMN1 loss at a fold change threshold of = 2.0 revealed expression
changes for 437 genes, of which 269 were up-regulated and 168 were
down-regulated. Microarray data and qRT-PCR analysis of mRNA expression
demonstrated changes in the message levels for STMN4, encoding RB3,
a protein related to stathmin, and in alterations to many tubulin
isotype mRNAs. KEGG Pathway analysis of the microarray data indicated
changes to cell motility-related genes, and qRT-PCR plates specific
for focal adhesion and ECM proteins generally confirmed the microarray
data. Several microtubule assembly regulators and motors were also
differentially regulated in STMN1-/- cells, but these changes should
not compensate for loss of stathmin.CONCLUSION:Approximately 50%
of genes up or down regulated (at a fold change of = 2) in STMN1-/-
mouse embryo fibroblasts function broadly in cell adhesion and motility.
These results support models indicating a role for stathmin in regulating
cell locomotion, but also suggest that this functional activity may
involve changes to the cohort of proteins expressed in the cell,
rather than as a direct consequence of stathmin-dependent regulation
of the microtubule cytoskeleton.},
doi = {10.1186/1471-2164-10-343},
issn = {1471-2164},
pubmedid = {19643027},
url = {http://www.biomedcentral.com/1471-2164/10/343}
}
@ARTICLE{Ringshausen2006,
author = {Ringshausen, Ingo and O'Shea, Clodagh C. and Finch, Andrew J. and
Swigart, Lamorna Brown and Evan, Gerard I.},
title = {Mdm2 is critically and continuously required to suppress lethal p53
activity in vivo},
journal = {Cancer Cell},
year = {2006},
volume = {10},
pages = {501--514},
number = {6},
month = dec,
abstract = {Summary There is currently much interest in the idea of restoring
p53 activity in tumor cells by inhibiting Hdm2/Mdm2. However, it
has remained unclear whether this would also activate p53 in normal
cells. Using a switchable endogenous p53 mouse model, which allows
rapid and reversible toggling of p53 status between wild-type and
null states, we show that p53 is spontaneously active in all tested
tissues of mdm2-deficient mice, triggering fatal pathologies that
include ablation of classically radiosensitive tissues. In apoptosis-resistant
tissues, spontaneous unbuffered p53 activity triggers profound inhibition
of cell proliferation. Such acute spontaneous p53 activity occurs
in the absence of any detectable p53 posttranslational modification,
DNA damage, or p19ARF signaling and triggers rapid p53 degradation.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-4MJBN1N-8/2/a10cdfb9c755218ebddeb4160367cc5f}
}
@ARTICLE{Rink2009,
author = {Rink, Lori and Skorobogatko, Yuliya and Kossenkov, Andrew V. and
Belinsky, Martin G. and Pajak, Thomas and Heinrich, Michael C. and
Blanke, Charles D. and von Mehren, Margaret and Ochs, Michael F.
and Eisenberg, Burton and Godwin, Andrew K.},
title = {Gene expression signatures and response to imatinib mesylate in gastrointestinal
stromal tumor},
journal = {Mol. Cancer Ther.},
year = {2009},
volume = {8},
pages = {2172--2182},
number = {8},
month = aug,
abstract = {Despite initial efficacy of imatinib mesylate in most gastrointestinal
stromal tumor (GIST) patients, many experience primary/secondary
drug resistance. Therefore, clinical management of GIST may benefit
from further molecular characterization of tumors before and after
imatinib mesylate treatment. As part of a recent phase II trial of
neoadjuvant/adjuvant imatinib mesylate treatment for advanced primary
and recurrent operable GISTs (Radiation Therapy Oncology Group S0132),
gene expression profiling using oligonucleotide microarrays was done
on tumor samples obtained before and after imatinib mesylate therapy.
Patients were classified according to changes in tumor size after
treatment based on computed tomography scan measurements. Gene profiling
data were evaluated with Statistical Analysis of Microarrays to identify
differentially expressed genes (in pretreatment GIST samples). Based
on Statistical Analysis of Microarrays [False Discovery Rate (FDR),
10%], 38 genes were expressed at significantly lower levels in the
pretreatment biopsy samples from tumors that significantly responded
to 8 to 12 weeks of imatinib mesylate, that is, >25% tumor reduction.
Eighteen of these genes encoded Kruppel-associated box (KRAB) domain
containing zinc finger (ZNF) transcriptional repressors. Importantly,
10 KRAB-ZNF genes mapped to a single locus on chromosome 19p, and
a subset predicted likely response to imatinib mesylate-based therapy
in a naive panel of GIST. Furthermore, we found that modifying expression
of genes within this predictive signature can enhance the sensitivity
of GIST cells to imatinib mesylate. Using clinical pretreatment biopsy
samples from a prospective neoadjuvant phase II trial, we have identified
a gene signature that includes KRAB-ZNF 91 subfamily members that
may be both predictive of and functionally associated with likely
response to short-term imatinib mesylate treatment. [Mol Cancer Ther
2009;8(8):2172-82]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/8/8/2172}
}
@ARTICLE{Rio2010,
author = {Rio, Donald C. and Ares, Manuel, Jr and Hannon, Gregory J. and Nilsen,
Timothy W.},
title = {Determining the Yield and Quality of Purified RNA},
journal = {Cold Spring Harb Protoc},
year = {2010},
volume = {2010},
pages = {pdb.top82--},
number = {6},
month = jun,
abstract = {After any RNA purification by any method, it is necessary to ascertain
both the amount (yield) and the integrity (quality) of the RNA obtained.
This is essential for any subsequent analysis and critical for any
comparative analyses. This article discusses several methods for
RNA quantitation and provides tips for each.},
url = {http://cshprotocols.cshlp.org/cgi/content/abstract/2010/6/pdb.top82}
}
@ARTICLE{RIOJA2004,
author = {RIOJA, I. and BUSH, K. A. and BUCKTON, J. B. and DICKSON, M. C. and
LIFE, P. F.},
title = {Joint cytokine quantification in two rodent arthritis models: kinetics
of expression, correlation of mRNA and protein levels and response
to prednisolone treatment},
journal = {Clinical \& Experimental Immunology},
year = {2004},
volume = {137},
pages = {65--73},
number = {1},
abstract = {SUMMARY Biomarker quantification in disease tissues from animal models
of rheumatoid arthritis (RA) can help to provide insights into the
mechanisms of action of novel therapeutic agents. In this study we
validated the kinetics of IL-1β, TNF-α and IL-6 mRNA and protein
expression levels in joints from DBA/1OlaHsd murine collagen-induced
arthritis (CIA) and Lewis rat Streptococcal cell wall (SCW)-induced
arthritis by real-time polymerase chain reaction (PCR) TaqMan® and
Enzyme-linked immunosorbent assay (ELISA). Prednisolone was used
as a reference to investigate any correlation between clinical response
and cytokine levels at selected time-points. To our knowledge this
is the first report showing a close pattern of expression between
mRNA and protein for IL-1β and IL-6, but not for TNF-α, in these
two models of RA. The kinetics of expression for these biomarkers
suggested that the optimal sampling time-points to study the effect
of compounds on both inflammation and cytokine levels were day 4
postonset in CIA and day 3 after i.v challenge in SCW-induced arthritis.
Prednisolone reduced joint swelling through a mechanism associated
with a reduction in IL-1β and IL-6 protein and mRNA expression levels.
At the investigated time points, protein levels for TNF-α in arthritic
joints were lower than the lower limit of detection of the ELISA,
whereas mRNA levels for this cytokine were reliably detected. These
observations suggest that RT-PCR TaqMan® is a sensitive technique
that can be successfully applied to the quantification of mRNA levels
in rodent joints from experimental arthritis models providing insights
into mechanisms of action of novel anti-inflammatory drugs.},
issn = {1365-2249},
keywords = {animal models, mice, rats, collagen-induced arthritis, SCW-induced
arthritis, cytokines, interleukins, prednisolone},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2249.2004.02499.x}
}
@ARTICLE{Rioja2007,
author = {Rioja, J. and Panizo, A. and Sola, J.J. and Brugarolas, X. and Saiz,
A. and Echeveste, J. and Lozano, M.D. and Robles, J.E. and Zudaire,
J.J. and Berian, J.M. and Pardo, F.J.},
title = {39 epithelial cell adhesion molecule (epcam) expression in renal
cell carcinomas (rcc). a tissue microarray study},
journal = {European Urology Supplements},
year = {2007},
volume = {6},
pages = {32--32},
number = {2},
month = mar,
booktitle = {22nd Annual Congress of the European Association of Urology},
issn = {1569-9056},
url = {http://www.sciencedirect.com/science/article/B6X11-4N44XS2-1H/2/69f19c44d2babe353c6c38dd36a86365}
}
@ARTICLE{Riou2007,
author = {Riou, Catherine and Yassine-Diab, Bader and Van grevenynghe, Julien
and Somogyi, Roland and Greller, Larry D. and Gagnon, Dominic and
Gimmig, Sylvain and Wilkinson, Peter and Shi, Yu and Cameron, Mark
J. and Campos-Gonzalez, Roberto and Balderas, Robert S. and Kelvin,
David and Sekaly, Rafick-Pierre and Haddad, Elias K.},
title = {Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation
and drives the survival of CD4+ central memory T cells},
journal = {J. Exp. Med.},
year = {2007},
volume = {204},
pages = {79--91},
number = {1},
month = jan,
abstract = {The molecular events involved in the establishment and maintenance
of CD4+ central memory and effector memory T cells (TCM and TEM,
respectively) are poorly understood. In this study, we demonstrate
that ex vivo isolated TCM are more resistant to both spontaneous
and Fas-induced apoptosis than TEM and have an increased capacity
to proliferate and persist in vitro. Using global gene expression
profiling, single cell proteomics, and functional assays, we show
that the survival of CD4+ TCM depends, at least in part, on the activation
and phosphorylation of signal transducer and activator of transcription
5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant
increase in the levels of phosphorylation of STAT5a compared with
TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the
latter is well known for its capacity to enhance T cell survival.
Moreover, ex vivo TCM express higher levels of the transcriptionally
inactive phosphorylated forms of FOXO3a and concomitantly lower levels
of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking
FOXO3a phosphorylation confirmed the role of this phosphoprotein
in protecting TCM from apoptosis. Our results provide, for the first
time in humans, an insight into molecular mechanisms that could be
responsible for the longevity and persistence of CD4+ TCM.},
url = {http://jem.rupress.org/cgi/content/abstract/204/1/79}
}
@ARTICLE{Riou2010,
author = {Riou, Mickaël and Carbonnelle, Sylviane and Avrain, Laëtitia and
Mesaros, Narcisa and Pirnay, Jean-Paul and Bilocq, Florence and De
Vos, Daniel and Simon, Anne and Piérard, Denis and Jacobs, Frédérique
and Dediste, Anne and Tulkens, Paul M. and Van Bambeke, Françoise
and Glupczynski, Youri},
title = {In vivo development of antimicrobial resistance in Pseudomonas aeruginosa
strains isolated from the lower respiratory tract of Intensive Care
Unit patients with nosocomial pneumonia and receiving antipseudomonal
therapy},
journal = {International Journal of Antimicrobial Agents},
year = {2010},
volume = {36},
pages = {513--522},
number = {6},
month = dec,
abstract = {Pseudomonas aeruginosa causes severe nosocomial pneumonia in Intensive
Care Unit (ICU) patients, with an increased prevalence of multiresistant
strains. We examined the impact of the use of antipseudomonal antibiotic(s)
on the susceptibility of P. aeruginosa isolated from ICU patients
with clinically suspected hospital-acquired pneumonia collected in
five teaching hospitals (110 non-duplicate initial isolates; 62 clonal
pairs of initial and last isolates during treatment). Minimum inhibitory
concentrations (MICs) were determined for amikacin, ciprofloxacin,
meropenem, piperacillin/tazobactam (TZP), cefepime and ceftazidime
(used in therapy) as well as five reporter antibiotics (aztreonam,
colistin, gentamicin, piperacillin and ticarcillin) using Clinical
and Laboratory Standards Institute (CLSI) methodology. Susceptibility
was assessed according to European Committee on Antimicrobial Susceptibility
Testing (EUCAST) and CLSI breakpoints. Resistance rates prior to
treatment exceeded 25% for cefepime, ceftazidime, piperacillin, ticarcillin
and aztreonam (EUCAST and CLSI) and for gentamicin, TZP and colistin
(EUCAST only). The highest rates of cross-resistance were noted for
ceftazidime and cefepime and the lowest rate for amikacin. Mean MIC
values were systematically higher in isolates from patients previously
exposed (1 month) to the corresponding antibiotic. For clonal pairs,
a systematic increase in MIC between initial and last isolates (significant
for amikacin, cefepime, meropenem and TZP) was noted. There was a
significant correlation between the use of antibiotics (adjusted
for respective proportional use of each drug) and loss of susceptibility
at the population level when using EUCAST breakpoints. The high level
of resistance of P. aeruginosa in ICU patients with nosocomial pneumonia
as well as its further increase during treatment severely narrows
the already limited therapeutic options. Further observational studies
and the development of early diagnosis for resistant isolates are
warranted.},
issn = {0924-8579},
keywords = {Pseudomonas aeruginosa, Nosocomial pneumonia, Susceptibility, Resistance,
Antibiotics},
url = {http://www.sciencedirect.com/science/article/pii/S0924857910003547}
}
@ARTICLE{Ripka2007,
author = {Ripka, S and Konig, A and Buchholz, M and Wagner, M and Sipos, B
and Kloppel, G and Downward, J and Gress, TM and Michl, P},
title = {WNT5A--target of CUTL1 and potent modulator of tumor cell migration
and invasion in pancreatic cancer},
journal = {Carcinogenesis},
year = {2007},
volume = {28},
pages = {1178--1187},
number = {6},
month = jun,
abstract = {Previously, we have identified the transcription factor CUTL1 as an
important mediator of tumor invasion and target of tumor growth factor-beta.
Using high-throughput approaches, we identified several putative
downstream effectors of CUTL1, among them WNT5A, a secreted member
of the Wnt multigene family. The aim of this study was to investigate
the role of WNT5A as a novel target of CUTL1 in pancreatic cancer.
CUTL1 and WNT5A were stably over-expressed as well as transiently
and stably knocked down by RNA interference. Effects on proliferation,
migration and invasiveness were investigated by thymidine incorporation,
Boyden chamber experiments and time-lapse microscopy. Expression
of WNT5A in pancreatic cancer tissues was analyzed by real-time polymerase
chain reaction (RT-PCR) and immunohistochemistry. We found that CUTL1
transcriptionally up-regulated WNT5A on RNA, protein and promoter
level. WNT5A significantly enhanced migration, proliferation and
invasiveness, mediating the pro-invasive effects of CUTL1 to a major
extent. WNT5A effects were accompanied by a marked modulation of
marker genes associated with epithelial-mesenchymal transition. Using
RT-PCR and immunohistochemistry, we found that WNT5A is up-regulated
early during pancreatic cancerogenesis in pancreatic intraepithelial
neoplasias lesions and in invasive pancreatic adenocarcinomas, as
compared with normal pancreas tissues. These data identify WNT5A
as important target of CUTL1 and as novel mediator of invasiveness
and tumor progression in pancreatic cancer.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/28/6/1178}
}
@ARTICLE{Ripperger2007,
author = {Ripperger, Tim and von Neuhoff, Nils and Kamphues, Kathrin and Emura,
Makito and Lehmann, Ulrich and Tauscher, Marcel and Schraders, Margit
and Groenen, Patricia and Skawran, Britta and Rudolph, Cornelia and
Callet-Bauchu, Evelyne and van Krieken, Johan H.J.M. and Schlegelberger,
Brigitte and Steinemann, Doris},
title = {Promoter methylation of PARG1, a novel candidate tumor suppressor
gene in mantle cell lymphomas},
journal = {Haematologica},
year = {2007},
volume = {92},
pages = {460--468},
number = {4},
month = apr,
abstract = {Background and ObjectivesMantle cell lymphoma (MCL), a mature B-cell
neoplasm, is genetically characterized by the translocation t(11;14)(q13;q32).
However, secondary alterations are required for malignant transformation.
The identification of inactivated tumor suppressor genes contributing
to the development of MCL may lead to further elucidation of the
biology of this disease and help to identify novel targets for therapy.
Design and MethodsWhole genome microarray-based gene expression profiling
on treated versus untreated MCL cell lines was used to identify genes
induced by 5-aza-2'-deoxycytidine. The degree of promoter methylation
and transcriptional silencing of selected genes was then proven in
MCL cell lines and primary cases by methylation-specific polymerase
chain reaction (PCR) techniques, real-time PCR and gene expression
profiling. ResultsAfter 5-aza-2'-deoxycytidine treatment, we identified
more than 1000 upregulated genes, 16 of which were upregulated [≥]3-fold.
Most of them were not known to be silenced by methylation in MCL.
A low expression of ING1, RUNX3 and BNIP3L was observed in three
of the five the MCL cell lines. In addition, the expression of PARG1,
which is located in the frequently deleted region 1p22.1, was substantially
reduced and displayed at least partial promoter methylation in all
investigated MCL cell lines as well as in 31 primary MCL cases. Interpretation
and ConclusionsIn summary, we identified interesting novel candidate
genes that probably contribute to the progression of MCL and suggest
that PARG1 is a strong candidate tumor suppressor gene in MCL.},
url = {http://www.haematologica.org/cgi/content/abstract/92/4/460}
}
@ARTICLE{Risbano2010,
author = {Risbano, Michael G and Meadows, Christina A. and Coldren, Christopher
D. and Jenkins, Tiffany J. and Edwards, Michael G. and Collier, David
and Huber, Wendy and Mack, Douglas G. and Fontenot, Andrew P. and
Geraci, Mark W. and Bull, Todd M},
title = {Altered Immune Phenotype in Peripheral Blood Cells of Patients with
Scleroderma-Associated Pulmonary Hypertension},
journal = {Clinical and Translational Science},
year = {2010},
volume = {3},
pages = {210--218},
number = {5},
abstract = {Abstract Pulmonary arterial hypertension is a common and fatal complication
of scleroderma that may involve inflammatory and autoimmune mechanisms.
Alterations in the gene expression of peripheral blood mononuclear
cells have been previously described in patients with pulmonary arterial
hypertension. Our goal is to identify differentially expressed genes
in peripheral blood mononuclear cells in scleroderma patients with
and without pulmonary hypertension as biomarkers of disease. Gene
expression analysis was performed on a Microarray Cohort of scleroderma
patients with (n= 10) and without (n= 10) pulmonary hypertension.
Differentially expressed genes were confirmed in the Microarray Cohort
and validated in a Validation Cohort of scleroderma patients with
(n= 15) and without (n= 19) pulmonary hypertension by RT-qPCR. We
identified inflammatory and immune-related genes including interleukin-7
receptor (IL-7R) and chemokine receptor 7 as differentially expressed
in patients with scleroderma-associated pulmonary hypertension. Flow
cytometry confirmed decreased expression of IL-7R on circulating
CD4+ T-cells from scleroderma patients with pulmonary hypertension.
Differences exist in the expression of inflammatory and immune-related
genes in peripheral blood cells from patients with scleroderma-related
pulmonary hypertension compared to those with normal pulmonary artery
pressures. These findings may have implications as biomarkers to
screen at-risk populations for early diagnosis and provide insight
into mechanisms of scleroderma-related pulmonary hypertension. Clin
Trans Sci 2010; Volume 3: 210–218},
issn = {1752-8062},
keywords = {pulmonary hypertension, gene array, gene expression, interleukins,
inflammation},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1752-8062.2010.00218.x}
}
@ARTICLE{Risbud2011,
author = {Rashmi M. Risbud and Carolyn Lee and Brenda E. Porter},
title = {Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus},
journal = {Brain Research},
year = {2011},
volume = {1424},
pages = {53 - 59},
number = {0},
abstract = {Status epilepticus induces a cascade of protein expression changes
contributing to the subsequent development of epilepsy. By identifying
the cascade of molecular changes that contribute to the development
of epilepsy we hope to be able to design therapeutics for preventing
epilepsy. MicroRNAs influence gene expression by altering mRNA stability
and/or translation and have been implicated in the pathology of multiple
diseases. MiR21 and its co-transcript miR21*, microRNAs produced
from either the 5′ or 3′ ends of the same precursor RNA strand,
are increased in the hippocampus following status epilepticus.
We have identified a miR21 binding site, in the 3′ UTR of neurotrophin-3
that inhibits translation. Neurotrophin-3 mRNA levels decrease in
the hippocampus following SE concurrent with the increase in miR21.
MiR21 levels in cultured hippocampal neurons inversely correlate
with neurotrophin-3 mRNA levels. Treatment of hippocampal neuronal
cultures with excess K+Cl−, a depolarizing agent mimicking the
episode of status epilepticus, also results in an increase in miR21
and a decrease in neurotrophin-3 mRNA. MiR21 is a candidate for regulating
neurotrophin-3 signaling in the hippocampus following status epilepticus.},
doi = {10.1016/j.brainres.2011.09.039},
issn = {0006-8993},
keywords = {Epilepsy},
url = {http://www.sciencedirect.com/science/article/pii/S0006899311017677}
}
@BOOK{Rise2007,
title = {Salmonid DNA Microarrays and Other Tools for Functional Genomics
Research},
publisher = {Blackwell Publishing Ltd},
year = {2007},
author = {Rise, Matthew L. and von Schalburg, Kristian R. and Cooper, Glenn
A. and Koop, Ben F.},
pages = {369--412},
abstract = {Summary 10.1002/9780470277560.ch22.abs This chapter contains section
titled:},
booktitle = {Aquaculture Genome Technologies},
issn = {9780470277560},
keywords = {DNA, microarrays, functional genomics, gene discovery, tetraploid
organisms},
url = {http://dx.doi.org/10.1002/9780470277560.ch22}
}
@ARTICLE{Riserus2008,
author = {Riserus, Ulf and Sprecher, Dennis and Johnson, Tony and Olson, Eric
and Hirschberg, Sandra and Liu, Aixue and Fang, Zeke and Hegde, Priti
and Richards, Duncan and Sarov-Blat, Leli and Strum, Jay C. and Basu,
Samar and Cheeseman, Jane and Fielding, Barbara A. and Humphreys,
Sandy M. and Danoff, Theodore and Moore, Niall R. and Murgatroyd,
Peter and O'Rahilly, Stephen and Sutton, Pauline and Willson, Tim
and Hassall, David and Frayn, Keith N. and Karpe, Fredrik},
title = {Activation of Peroxisome Proliferator-Activated Receptor (PPAR){delta}
Promotes Reversal of Multiple Metabolic Abnormalities, Reduces Oxidative
Stress, and Increases Fatty Acid Oxidation in Moderately Obese Men},
journal = {Diabetes},
year = {2008},
volume = {57},
pages = {332--339},
number = {2},
month = feb,
abstract = {OBJECTIVE-- Pharmacological use of peroxisome proliferator-activated
receptor (PPAR){delta} agonists and transgenic overexpression of
PPAR{delta} in mice suggest amelioration of features of the metabolic
syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize
a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS--
The PPAR{delta} agonist (10 mg o.d. GW501516), a comparator PPAR{alpha}
agonist (20 {micro}g o.d. GW590735), and placebo were given in a
double-blind, randomized, three-parallel group, 2-week study to six
healthy moderately overweight subjects in each group. Metabolic evaluation
was made before and after treatment including liver fat quantification,
fasting blood samples, a 6-h meal tolerance test with stable isotope
fatty acids, skeletal muscle biopsy for gene expression, and urinary
isoprostanes for global oxidative stress. RESULTS-- Treatment with
GW501516 showed statistically significant reductions in fasting plasma
triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%),
and insulin (-11%), whereas HDL cholesterol was unchanged. A 20%
reduction in liver fat content (P < 0.05) and 30% reduction in urinary
isoprostanes (P = 0.01) were also observed. Except for a lowering
of triglycerides (-30%, P < 0.05), none of these changes were observed
in response to GW590735. The relative proportion of exhaled CO2 directly
originating from the fat content of the meal was increased (P < 0.05)
in response to GW501516, and skeletal muscle expression of carnitine
palmitoyl-transferase 1b (CPT1b) was also significantly increased.
CONCLUSIONS-- The PPAR{delta} agonist GW501516 reverses multiple
abnormalities associated with the metabolic syndrome without increasing
oxidative stress. The effect is probably caused by increased fat
oxidation in skeletal muscle.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/57/2/332}
}
@ARTICLE{Ritchie2007,
author = {Ritchie, Kenneth J. and Henderson, Colin J. and Wang, Xiu Jun and
Vassieva, Olga and Carrie, Dianne and Farmer, Peter B. and Gaskell,
Margaret and Park, Kevin and Wolf, C. Roland},
title = {Glutathione Transferase {pi} Plays a Critical Role in the Development
of Lung Carcinogenesis following Exposure to Tobacco-Related Carcinogens
and Urethane},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {9248--9257},
number = {19},
month = oct,
abstract = {Human cancer is controlled by a complex interaction between genetic
and environmental factors. Such environmental factors are well defined
for smoking-induced lung cancer; however, the roles of specific genes
have still to be elucidated. Glutathione transferase {pi} (GSTP)
catalyzes the detoxification of electrophilic diol epoxides produced
by the metabolism of polycyclic aromatic hydrocarbons such as benzo[a]pyrene
(BaP), a common constituent of tobacco smoke. Activity-altering polymorphisms
in Gstp have therefore been speculated to be potential risk modifiers
in lung cancer development. To clearly establish a role for GSTP
in lung tumorigenesis, we investigated whether deletion of the murine
Gstp genes (Gstp1 and Gstp2) alters susceptibility to chemically
induced lung tumors following exposure to BaP, 3-methylcholanthrene
(3-MC), and urethane. Gstp-null mice were found to have substantially
increased numbers of adenomas relative to wild-type mice following
exposure to all three compounds (8.3-, 4.3-, and 8.7-fold increase
for BaP, 3-MC, and urethane, respectively). In Gstp-null mice, the
capacity of pulmonary cytosol to catalyze conjugation of the BaP
diol epoxide was significantly reduced. Concomitant with this, a
significant increase in the level of BaP DNA adducts was measured
in the lungs of null animals; however, no increase in DNA adducts
was measured in the case of 3-MC exposure, suggesting that an alternative
protective pathway exists. Indeed, significant differences in pulmonary
gene expression profiles were also noted between wild-type and null
mice. This is the first report to establish a clear correlation between
Gstp status and lung cancer in vivo. [Cancer Res 2007;67(19):9248-57]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/19/9248}
}
@ARTICLE{Ritchie2009,
author = {Ritchie, Kenneth J. and Walsh, Shaun and Sansom, Owen J. and Henderson,
Colin J. and Wolf, C. Roland},
title = {Markedly enhanced colon tumorigenesis in ApcMin mice lacking glutathione
S-transferase Pi},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {20859--20864},
number = {49},
month = dec,
abstract = {Glutathione transferases are a multigene family of proteins that catalyze
the conjugation of toxic electrophiles and carcinogens to glutathione.
Glutathione transferase Pi (GSTP) is commonly overexpressed in human
tumors and there is emerging evidence that the enzyme has additional
cellular functions in addition to its role in drug and carcinogen
detoxification. To investigate the unique functions of this enzyme,
we have crossed Gstp null mice with an initiated model of colon cancer,
the ApcMin mouse. In contrast to the ApcMin/+ Gstp1/p2+/+ (Gstp-wt
ApcMin) mice, which rarely develop colonic tumours, ApcMin/+Gstp1/p2-/-
(Gstp-null ApcMin) mice had a 6-fold increase in colon adenoma incidence,
and a 50-fold increase in colorectal adenoma multiplicity, relative
to Gstp-wt ApcMin. This increase was associated with early tumor
onset and decreased survival. Analysis of the biochemical changes
in the colon tissue of Gstp-null ApcMin mice demonstrated a marked
induction of many inflammatory genes, including IL-6, IL-4, IFN-{gamma},
and inducible nitric oxide synthase. In support of the induction
of inducible nitric oxide synthase, a profound induction of nitrotyrosine
adducts was observed. Gstp therefore appears to play a role in controlling
inflammatory responses in the colon, which would explain the change
in tumor incidence observed. These data also suggest that individual
variation in GSTP levels may be a factor in colon cancer susceptibility.},
url = {http://www.pnas.org/cgi/content/abstract/106/49/20859}
}
@ARTICLE{Ritorto2011,
author = {Ritorto, Maria Stella and Borlak, Jürgen},
title = {Combined Serum and Tissue Proteomic Study Applied to a c-Myc Transgenic
Mouse Model of Hepatocellular Carcinoma Identified Novel Disease
Regulated Proteins Suitable for Diagnosis and Therapeutic Intervention
Strategies},
journal = {Journal of Proteome Research},
year = {2011},
volume = {10},
pages = {3012-3030},
number = {7},
abstract = { Hepatocellular carcinoma (HCC) is the third leading cause of cancer
death in the U.S. Notably, most HCCs display c-Myc hyperactivity
but this transcription factor participates in the regulation of as
many as 15−20% of genes of the human genome. To better understand
its oncogenic activity, a mass spectrometry-based proteomic approach
was employed to search for disease-regulated proteins in liver tissue
and serum of c-Myc transgenic mice that specifically developed HCC.
Overall, a total of 90 differentially expressed proteins were identified
with retinol binding protein 4, transthyretin, major urinary protein
family, apolipoprotein E, and glutathione peroxidase being regulated
in common in tissue and serum of HCC mice. Importantly, this study
identified n = 22 novel tumor tissue-regulated proteins to function
in cell cycle and proliferation, nucleotide and ribosomal biogenesis,
oxidative stress, and GSH metabolism, while bioinformatics revealed
the coding sequences of regulated proteins to enharbour c-Myc binding
sites. Translation of the findings to human disease was achieved
by Western immunoblotting of serum proteins and by immunohistochemistry
of human HCC. Taken collectively, our study helps to define a c-Myc
proteome suitable for diagnostic and possible therapeutic intervention
strategies. },
doi = {10.1021/pr101207t},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr101207t},
url = {http://pubs.acs.org/doi/abs/10.1021/pr101207t}
}
@ARTICLE{Ritorto2011a,
author = {Ritorto, Maria Stella And Borlak, Juergen},
title = {A combined serum and tissue proteomic study applied to a c-Myc transgenic
mouse model of hepatocellular carcinoma identified novel disease
regulated proteins suitable for diagnosis and therapeutic intervention
strategies},
journal = {Journal of Proteome Research},
year = {2011},
volume = {0},
number = {ja},
doi = {10.1021/pr101207t},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr101207t},
url = {http://pubs.acs.org/doi/abs/10.1021/pr101207t}
}
@ARTICLE{Ritter2005,
author = {Ritter, Mirko and Göggel, Rolf and Chaudhary, Nveed and Wiedenmann,
Alexander and Jung, Birgit and Weith, Andreas and Seither, Peter},
title = {Elevated expression of TARC (CCL17) and MDC (CCL22) in models of
cigarette smoke-induced pulmonary inflammation},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {334},
pages = {254--262},
number = {1},
month = aug,
abstract = {TARC (CCL17) and MDC (CCL22) are well-known chemoattractants for Th2
cells. Here, we evaluated the role of both chemokines for cigarette
smoke-induced airway inflammation. The expression profiles of MDC,
TARC, and their receptor CCR4 were analyzed in models of acute and
chronic cigarette smoke-induced airway inflammation that is characterized
by a Th1 immune response. The results were compared to the expression
of both chemokines in models of idiopathic pulmonary fibrosis and
acute asthma, which are associated with a Th2 immune response. The
expression of MDC and TARC was found to be elevated in all lung inflammation
models. In contrast to the findings in the asthma and lung fibrosis
models, the increased expression of MDC and TARC in the cigarette-smoke
model was not associated with an increased infiltration of Th2 cells
into smoke-treated lungs. Our data indicate that instead of Th2 cells,
airway epithelial cells expressing CCR4 might be the principal targets
for MDC and TARC released from alveolar macrophages during cigarette
smoke-induced airway inflammation.},
issn = {0006-291X},
keywords = {Cigarette smoke, Airway inflammation, Bronchial epithelium, COPD,
CCR4, MDC, TARC},
url = {http://www.sciencedirect.com/science/article/B6WBK-4GGWDH1-7/2/67156d6cb86d45ef4ef54a1ea370bb6b}
}
@ARTICLE{Rival2009,
author = {Rival, Yves and Puech, Laurence and Taillandier, Thierry and Benéteau,
Nathalie and Rouquette, Anne and Lestienne, Fabrice and Dupont-Passelaigue,
Elisabeth and Le Roy, Isabelle and Patoiseau, Jean-François and Junquéro,
Didier},
title = {PPAR activators and COX inhibitors selectively block cytokine-induced
COX-2 expression and activity in human aortic smooth muscle cells},
journal = {European Journal of Pharmacology},
year = {2009},
volume = {606},
pages = {121--129},
number = {1-3},
month = mar,
abstract = {Atherosclerotic complications are related to the unstable character
of the plaque rather than its volume. Vulnerable plaques often contain
a large lipid core, a reduced content of smooth muscle cells (SMCs),
and an accumulation of inflammatory cells. Regulation of this inflammatory
response is an essential element in chronic inflammatory diseases
such as atherosclerosis. Nuclear receptors and particularly peroxisome
proliferator-activated receptors (PPARs) have emerged as therapeutic
targets with a widespread impact on the treatment of metabolic disorders
because they can modulate gene expression involved in lipid and glucose
homeostasis and can exert anti-inflammatory properties. However,
little is known about nuclear receptor effects on SMC inflammation,
which produces large amounts of IL-6 and prostanoids. The aim of
this study was to evaluate anti-inflammatory properties of nuclear
receptor activators in a human physiological SMC model. We show that
PPAR activators, as well as liver X receptor [alpha], farnesoid X
receptor and retinoid X receptor [alpha] activators, inhibit IL-1[beta]-induced
SMC 6-keto PGF1[alpha] synthesis, an index of cyclooxygenase (COX)-2
activity, with IC50 between 1 and 69 µM. In contrast, PPAR[gamma]
activators, as exemplified by rosiglitazone and pioglitazone, were
unable to inhibit cytokine-induced 6-keto PGF1[alpha] synthesis.
We also demonstrate for the first time that the COX-2 inhibitor rofecoxib
can reduce 6-keto PGF1[alpha] production by both enzymatic inhibition
and transcriptional repression. These results show that some nuclear
receptor activators have SMC anti-inflammatory properties due to
COX-2 inhibition which could participate in their anti-atherosclerotic
properties beyond lipid impacts.},
issn = {0014-2999},
keywords = {Atherosclerosis, Inflammation, PPAR (peroxisome proliferator-activated
receptor), COX, Smooth muscle cell},
url = {http://www.sciencedirect.com/science/article/B6T1J-4VDY83M-B/2/bc1a11e040b06cbe316df289db74bbe0}
}
@ARTICLE{Rivard2007,
author = {Rivard, Christopher J. and Brown, Lewis M. and Almeida, Nestor E.
and Maunsbach, Arvid B. and Pihakaski-Maunsbach, Kaarina and Andres-Hernando,
Ana and Capasso, Juan M. and Berl, Tomas},
title = {Expression of the Calcium-binding Protein S100A4 Is Markedly Up-regulated
by Osmotic Stress and Is Involved in the Renal Osmoadaptive Response},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {6644--6652},
number = {9},
month = mar,
abstract = {Proteomic analysis of Inner Medullary Collecting Duct (IMCD3) cells
adapted to increasing levels of tonicity (300, 600, and 900 mosmol/kg
H2O) by two-dimensional difference gel electrophoresis and mass spectrometry
revealed several proteins as yet unknown to be up-regulated in response
to hypertonic stress. Of these proteins, one of the most robustly
up-regulated (22-fold) was S100A4. The identity of the protein was
verified by high pressure liquid chromatography-mass spectrometry.
Western blot analysis confirmed increased expression with increased
tonicity, both acute and chronic. S100A4 protein expression was further
confirmed by immunocytochemical analysis. Cells grown in isotonic
conditions showed complete absence of immunostaining, whereas chronically
adapted IMCD3 cells had uniform cytoplasmic localization. The protein
is also regulated in vivo as in mouse kidney tissues S100A4 expression
was many -fold greater in the papilla as compared with the cortex
and increased further in the papilla upon 36 h of thirsting. Increased
expression of S100A4 was also observed in the medulla and papilla,
but not the cortex of a human kidney. Data from Affymetrix gene chip
analysis and quantitative PCR also revealed increased S100A4 message
in IMCD3 cells adapted to hypertonicity. The initial expression of
message increased at 8-10 h following exposure to acute sublethal
hypertonic stress (550 mosmol/kg H2O). Protein and message half-life
in IMCD3 cells were 85.5 and 6.8 h, respectively. Increasing medium
tonicity with NaCl, sucrose, mannitol, and choline chloride stimulated
S100A4 expression, whereas urea did not. Silencing of S100A4 expression
using a stable siRNA vector (pSM2; Open Biosystems) resulted in a
48-h delay in adaptation of IMCD3 cells under sublethal osmotic stress,
suggesting S100A4 is involved in the osmoadaptive response. In summary,
we describe the heretofore unrecognized up-regulation of a small
calcium-binding protein, both in vitro and in vivo, whose absence
profoundly delays osmoadaptation and slows cellular growth under
hypertonic conditions.},
url = {http://www.jbc.org/cgi/content/abstract/282/9/6644}
}
@ARTICLE{Riveira-Munoz2007,
author = {Riveira-Munoz, Eva and Chang, Qing and Godefroid, Nathalie and Hoenderop,
Joost G. and Bindels, Rene J. and Dahan, Karin and Devuyst, Olivier
and for the Belgian Network for the Study of Gitelman Syndrome},
title = {Transcriptional and Functional Analyses of SLC12A3 Mutations: New
Clues for the Pathogenesis of Gitelman Syndrome},
journal = {J. Am. Soc. Nephrol.},
year = {2007},
volume = {18},
pages = {1271--1283},
number = {4},
month = apr,
abstract = {Gitelman syndrome (GS) is a recessive salt-losing tubulopathy that
is caused by mutations in the SLC12A3 gene that encodes the sodium-chloride
co-transporter (NCC). GS is characterized by significant inter- and
intrafamilial phenotype variability, with early onset and/or severe
clinical manifestations in some patients. No correlations between
the disease variability and the position/nature of SLC12A3 mutations
have been investigated thus far. In this study, extensive mutational
analyses of SLC12A3 were performed in 27 patients with GS, including
genomic DNA sequencing, multiplex ligation-dependent probe amplification,
cDNA analysis, and quantification of allele-specific transcripts,
in parallel with functional analyses in Xenopus laevis oocytes and
detailed phenotyping. Twenty-six SLC12A3 mutations were identified
in 25 patients with GS, including eight novel (detection rate 80%).
Transcript analysis demonstrated that splicing mutations of SLC12A3
lead to frameshifted mRNA subject to degradation by nonsense-mediated
decay. Heterologous expression documented a novel class of NCC mutants
with defective intrinsic transport activity. A subgroup of patients
presented with early onset, growth retardation, and/or detrimental
manifestations, confirming the potential severity of GS. The mutations
that were associated with a severe presentation were the combination
at least for one allele of a missplicing resulting in a truncated
transcript that was downregulated by nonsense-mediated decay or a
nonfunctional, cell surface-absent mutant. The most recurrent mutation
on the second allele was a newly described NCC mutant that affected
the functional properties of the co-transporter. These data suggest
that the nature/position of SLC12A3 mutation, combined with male
gender, is a determinant factor in the severity of GS and provide
new insights in the underlying pathogenic mechanisms of the disease.},
url = {http://jasn.asnjournals.org/cgi/content/abstract/18/4/1271}
}
@ARTICLE{Rivera-Ruiz2010,
author = {Rivera-Ruiz, Marielis and Rodríguez-Quiñones, José and Akamine, Pearl
and Rodríguez-Medina, José},
title = {Post-transcriptional regulation in the myo1? mutant of Saccharomyces
cerevisiae },
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {690},
number = {1},
abstract = {BACKGROUND:Saccharomyces cerevisiae myosin type II-deficient (myo1?)
strains remain viable and divide, despite the absence of a cytokinetic
ring, by activation of the PKC1-dependent cell wall integrity pathway
(CWIP). Since the myo1? transcriptional fingerprint is a subset of
the CWIP fingerprint, the myo1? strain may provide a simplified paradigm
for cell wall stress survival.RESULTS:To explore the post-transcriptional
regulation of the myo1? stress response, 1,301 differentially regulated
ribosome-bound mRNAs were identified by microarray analysis of which
204 were co-regulated by transcription and translation. Four categories
of mRNA were significantly affected - protein biosynthesis, metabolism,
carbohydrate metabolism, and unknown functions. Nine genes of the
20 CWIP fingerprint genes were post-transcriptionally regulated.
Down and up regulation of selected ribosomal protein and cell wall
biosynthesis mRNAs was validated by their distribution in polysomes
from wild type and myo1? strains. Western blot analysis revealed
accumulation of the phosphorylated form of eukaryotic translation
initiation factor 2 (eIF2a-P) and a reduction in the steady state
levels of the translation initiation factor eIF4Gp in myo1? strains.
Deletion of GCN2 in myo1? abolished eIF2ap phosphorylation, and showed
a severe growth defect. The presence of P-bodies in myo1? strains
suggests that the process of mRNA sequestration is active, however,
the three representative down regulated RP mRNAs, RPS8A, RPL3 and
RPL7B were present at equivalent levels in Dcp2p-mCh-positive immunoprecipitated
fractions from myo1? and wild type cells. These same RP mRNAs were
also selectively co-precipitated with eIF2a-P in myo1? strains.CONCLUSIONS:Quantitative
analysis of ribosome-associated mRNAs and their polyribosome distributions
suggests selective regulation of mRNA translation efficiency in myo1?
strains. Inhibition of translation initiation factor eIF2a (eIF2a-P)
in these strains was by Gcn2p-dependent phosphorylation. The increase
in the levels of eIF2a-P; the genetic interaction between GCN2 and
MYO1; and the reduced levels of eIF4Gp suggest that other signaling
pathways, in addition to the CWIP, may be important for myo1? strain
survival. Selective co-immunoprecipitation of RP mRNAs with eIF2a-P
in myo1? strains suggests a novel mode of translational regulation.
These results indicate that post-transcriptional control is important
in the myo1? stress response and possibly other stresses in yeast.},
doi = {10.1186/1471-2164-11-690},
issn = {1471-2164},
pubmedid = {21126371},
url = {http://www.biomedcentral.com/1471-2164/11/690}
}
@ARTICLE{Rivero2010,
author = {Rivero, Rosa M. and Gimeno, Jacinta and Van Deynze, Allen and Walia,
Harkamal and Blumwald, Eduardo},
title = {Enhanced Cytokinin Synthesis in Tobacco Plants Expressing PSARK::IPT
Prevents the Degradation of Photosynthetic Protein Complexes During
Drought},
journal = {Plant Cell Physiol.},
year = {2010},
volume = {51},
pages = {1929--1941},
number = {11},
month = nov,
abstract = {To identify genes associated with the cytokinin-induced enhanced drought
tolerance, we analyzed the transcriptome of wild-type and transgenic
tobacco (Nicotiana tabacum SR1') plants expressing PSARK::IPT (for
senescence-associated receptor kinase::isopentenyltransferase) grown
under well-watered and prolonged water deficit conditions using the
tomato GeneChip. During water deficit, the expression of genes encoding
components of the carotenoid pathway leading to ABA biosynthesis
was enhanced in the wild-type plants, but repressed in the transgenic
plants. On the other hand, transgenic plants displayed higher transcript
abundance of genes involved in the brassinosteroid biosynthetic pathways.
Several genes coding for proteins associated with Chl synthesis,
light reactions, the Calvin-Benson cycle and photorespiration were
induced in the transgenic plants. Notably, increased transcript abundance
of genes associated with PSII, the cytochrome b6/f complex, PSI,
NADH oxidoreductase and the ATP complex was found in the PSARK::IPT
plants. The increased transcript abundance was assessed by quantitative
PCR and the increased protein levels were confirmed by Western blots.
Our results indicated that while the photosynthetic apparatus in
the wild-type plants was degraded, photosynthesis in the transgenic
plants was not affected and photosynthetic proteins were not degraded.
During water deficit, wild-type plants displayed a significant reduction
in electron transfer and photochemical quenching, with a marked increase
in non-photochemical quenching, suggesting a decrease in energy transfer
to the PSII core complexes and an increase in cyclic electron transfer
reactions.},
comment = {10.1093/pcp/pcq143},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/51/11/1929}
}
@ARTICLE{Rivieccio2005,
author = {Rivieccio, Mark A. and John, Gareth R. and Song, Xianyuan and Suh,
Hyeon-Sook and Zhao, Yongmei and Lee, Sunhee C. and Brosnan, Celia
F.},
title = {The Cytokine IL-1{beta} Activates IFN Response Factor 3 in Human
Fetal Astrocytes in Culture},
journal = {J. Immunol.},
year = {2005},
volume = {174},
pages = {3719--3726},
number = {6},
month = mar,
abstract = {The cytokine IL-1{beta} is a major activator of primary human fetal
astrocytes in culture, leading to the production of a wide range
of cytokines and chemokines important in the host defense against
pathogens. IL-1{beta}, like TLR4, signals via the MyD88/IL-1{beta}R-associated
kinase-1 pathway linked to activation of NF-{kappa}B and AP-1. Recent
studies have shown that TLR4 also signals independently of MyD88,
resulting in the activation of IFN regulatory factor 3 (IRF3), a
transcription factor required for the production of primary antiviral
response genes such as IFN-{beta}. Using a functional genomics approach,
we observed that IL-1{beta} induced in astrocytes a group of genes
considered to be IFN-stimulated genes (ISG), suggesting that IL-1{beta}
may also signal via IRF3 in these cells. We now show, using real-time
PCR, that in astrocytes IL-1{beta} induces the expression of IFN-{beta},
IRF7, CXCL10/IFN-{gamma}-inducible protein-10, and CCL5/RANTES. Chemokine
expression was confirmed by ELISA. We also show that IL-1{beta} induces
phosphorylation and nuclear translocation of IRF3 and delayed phosphorylation
of STAT1. The dependency of IFN-{beta}, IRF7, and CXCL10/IFN-{gamma}-inducible
protein-10 gene expression on IRF3 was confirmed using a dominant
negative IRF3-expressing adenovirus. The robust induction by IL-1{beta}
of additional ISG noted on the microarrays, such as STAT1, 2'5'-oligoadenylate
synthetase 2, and ISG15, also supports an active signaling role for
IL-1{beta} via this pathway in human fetal astrocytes. These data
are the first to show that IL-1{beta}, in addition to TLRs, can stimulate
IRF3, implicating this cytokine as an activator of genes involved
in innate antiviral responses in astrocytes.},
url = {http://www.jimmunol.org/cgi/content/abstract/174/6/3719}
}
@ARTICLE{Rivollier2012,
author = {Rivollier, Aymeric and He, Jianping and Kole, Abhisake and Valatas,
Vassilis and Kelsall, Brian L.},
title = {Inflammation switches the differentiation program of Ly6Chi monocytes
from antiinflammatory macrophages to inflammatory dendritic cells
in the colon},
journal = {J. Exp. Med.},
year = {2012},
pages = {jem.20101387},
abstract = {Dendritic cells (DCs) and macrophages (MPs) are important for immunological
homeostasis in the colon. We found that F4/80hiCX3CR1hi (CD11b+CD103-)
cells account for 80% of mouse colonic lamina propria MHC-IIhi cells.
Both CD11c+ and CD11c- cells within this population were identified
as MPs based on multiple criteria, including an MP transcriptome
revealed by microarray analysis. These MPs constitutively released
high levels of IL-10 at least partially in response to the microbiota
via an MyD88-independent mechanism. In contrast, cells expressing
low to intermediate levels of F4/80 and CX3CR1 were identified as
DCs based on phenotypic and functional analysis and comprise three
separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+
DCs, and CD103-CX3CR1intCD11b+ DCs. In noninflammatory conditions,
Ly6Chi monocytes (MOs) differentiated primarily into CD11c+ but not
CD11c- MPs. In contrast, during colitis, Ly6Chi MOs massively invaded
the colon and differentiated into proinflammatory CD103-CX3CR1intCD11b+
DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These
findings demonstrate the dual capacity of Ly6Chi blood MOs to differentiate
into either regulatory MPs or inflammatory DCs in the colon and that
the balance of these immunologically antagonistic cell types is dictated
by microenvironmental conditions.},
doi = {10.1084/jem.20101387},
eprint = {http://jem.rupress.org/cgi/reprint/jem.20101387v1.pdf},
url = {http://jem.rupress.org/cgi/content/abstract/jem.20101387v1}
}
@ARTICLE{Rivolta2006,
author = {Rivolta, Carlo and McGee, Terri L. and Frio, Thomas Rio and Jensen,
Roderick V. and Berson, Eliot L. and Dryja, Thaddeus P.},
title = {Variation in retinitis pigmentosa-11 (PRPF31 or RP11) gene expression
between symptomatic and asymptomatic patients with dominant RP11
mutations},
journal = {Hum. Mutat.},
year = {2006},
volume = {27},
pages = {644--653},
number = {7},
abstract = {Abstract 10.1002/humu.20325.abs Dominant mutations in the mRNA splicing
factor gene PRPF31 (RP11) cause retinitis pigmentosa with reduced
penetrance. We studied the expression of RP11 in lymphoblast cell
lines from 10 patients, including three who were clinically asymptomatic,
with six distinct RP11 mutations. Five of the six mutations were
characterized and all five created premature nonsense codons or eliminated
the normal initiation codon. Semiquantitative RT-PCR indicated that
an average of only 17% of the RP11 mRNA was derived from the mutant
allele, likely because the mutant mRNA transcripts were degraded
by nonsense-mediated decay. Gene expression levels were measured
by Affymetrix and CodeLink microarrays and, for RP11 transcripts,
also by real-time PCR. Combined wild-type-plus-mutant RP11 mRNA expression
from symptomatic patients was 52 to 77% of that in controls (p≤0.0005).
Clinically asymptomatic carriers had levels of RP11 mRNA similar
to controls and 29–42% higher than in clinically affected patients
(0.0001200 genes are expressed at a higher level in the dam strain,
while an additional mutation in mutS suppresses the induction of
many of the same genes. We also show by microarray and semiquantitative
real-time reverse transcription-PCR that both dam and dam mutS strains
show derepression of LexA-regulated SOS genes as well as the up-regulation
of other non-SOS genes involved in DNA repair. To correlate the level
of SOS induction and the up-regulation of genes involved in recombinational
repair with the level of DNA damage, we used neutral single-cell
electrophoresis to determine the number of double-strand breaks per
cell in each of the strains. We find that dam mutant E. coli strains
have a significantly higher level of double-strand breaks than the
other strains. We also observe a broad range in the number of double-strand
breaks in dam mutant cells, with a minority of cells showing as many
as 10 or more double-strand breaks. We propose that the up-regulation
of recombinational repair in dam mutants allows for the efficient
repair of double-strand breaks whose formation is dependent on functional
mismatch repair.},
url = {http://jb.asm.org/cgi/content/abstract/187/20/7027}
}
@ARTICLE{Robciuc2011,
author = {Robciuc, Marius R. and Naukkarinen, Jussi and Ortega-Alonso, Alfredo
and Tyynismaa, Henna and Raivio, Taneli and Rissanen, Aila and Kaprio,
Jaakko and Ehnholm, Christian and Jauhiainen, Matti and Pietilainen,
Kirsi H.},
title = {Serum angiopoietin-like 4 protein levels and expression in adipose
tissue are inversely correlated with obesity in monozygotic twins},
journal = {J. Lipid Res.},
year = {2011},
volume = {52},
pages = {1575-1582},
number = {8},
abstract = {Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates
adiposity through central and peripheral mechanisms. The aim of this
study was to investigate whether serum concentration and adipose
tissue expression of Angptl4 are associated with obesity-related
parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic
(MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16
cohorts. Among the MZ pairs, 21 were discordant for body mass index
(BMI) (intra-pair BMI-difference >2.5 kg/m2, age 23-33 years). Serum
Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue
gene expression was analyzed by genome-wide transcript profiling.
In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue
ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P
= 0.04 and P = 0.03, respectively) in obese twins as compared with
their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4
levels were inversely correlated with intra-pair differences in BMI
(r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression
was inversely correlated with BMI (r = -0.44, P = 0.001) and positively
correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41,
P = 0.005) expression. Our results demonstrated that variation in
Angptl4 concentration was only modestly accounted for by genetic
factors and suggest a role for Angptl4 in acquired obesity in humans},
doi = {10.1194/jlr.P015867},
eprint = {http://www.jlr.org/cgi/reprint/52/8/1575.pdf},
url = {http://www.jlr.org/cgi/content/abstract/52/8/1575}
}
@ARTICLE{Roberge2006,
author = {Roberge, Christian And Einum, Sigurd And Guderley, Helga And Bernatchez,
Louis},
title = {Rapid parallel evolutionary changes of gene transcription profiles
in farmed Atlantic salmon},
journal = {Molecular Ecology},
year = {2006},
volume = {15},
pages = {9--20},
number = {1},
abstract = {Abstract Farmed salmon strains have been selected to improve growth
rates as well as other traits of commercial interest but the 2 million
farmed salmon escaping annually may enhance the risk of extinction
of wild populations through genetic and ecological interactions.
Here, we compare the transcription profiles of 3557 genes in the
progeny of farmed and wild Atlantic salmon from Norway and Canada
grown in controlled conditions, and demonstrate that five to seven
generations of artificial selection led to heritable changes in gene
transcription profiles, the average magnitude of the differences
being 25% and 18% for at least 1.4% and 1.7% of the expressed genes
in juvenile salmon from Norway and Canada, respectively. Moreover,
genes showing significant transcription profile differences in both
farmed strains (16%) all exhibited parallel changes. These findings,
along with the identification of several genes whose expression profiles
were modified through artificial selection, provide new insights
into the molecular basis of parallel evolution, and suggest how gene
flow from farmed escapees may affect the genetic integrity of wild
populations.},
issn = {1365-294X},
keywords = {farmed salmon escapees, genome-wide transcription profiles, parallel
evolution, recent evolution, salmon breeding, salmon conservation},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2005.02807.x}
}
@ARTICLE{Robert2010,
author = {Robert, Claude},
title = {Microarray analysis of gene expression during early development:
a cautionary overview},
journal = {Reproduction},
year = {2010},
volume = {140},
pages = {787--801},
number = {6},
month = dec,
abstract = {The rise of the omics' technologies started nearly a decade ago and,
among them, transcriptomics has been used successfully to contrast
gene expression in mammalian oocytes and early embryos. The scarcity
of biological material that early developmental stages provide is
the prime reason why the field of transcriptomics is becoming more
and more popular with reproductive biologists. The potential to amplify
scarce mRNA samples and generate the necessary amounts of starting
material enables the relative measurement of RNA abundance of thousands
of candidates simultaneously. So far, microarrays have been the most
commonly used high-throughput method in this field. Microarray platforms
can be found in a wide variety of formats, from cDNA collections
to long or short oligo probe sets. These platforms generate large
amounts of data that require the integration of comparative RNA abundance
values in the physiological context of early development for their
full benefit to be appreciated. Unfortunately, significant discrepancies
between datasets suggest that direct comparison between studies is
difficult and often not possible. We have investigated the sample-handling
steps leading to the generation of microarray data produced from
prehatching embryo samples and have identified key steps that significantly
impact the downstream results. This review provides a discussion
on the best methods for the preparation of samples from early embryos
for microarray analysis and focuses on the challenges that impede
dataset comparisons from different platforms and the reasons why
methodological benchmarking performed using somatic cells may not
apply to the atypical nature of prehatching development.},
comment = {10.1530/REP-10-0191},
url = {http://www.reproduction-online.org/cgi/content/abstract/140/6/787}
}
@ARTICLE{Robert2011,
author = {Robert, Claude and Nieminen, Julie and Dufort, Isabelle and Gagné,
Dominic and Grant, Jason R. and Cagnone, Gaël and Plourde, Dany
and Nivet, Anne-Laure and Fournier, Éric and Paquet, Éric and Blazejczyk,
Michal and Rigault, Philippe and Juge, Nicolas and Sirard, Marc-André},
title = {Combining resources to obtain a comprehensive survey of the bovine
embryo transcriptome through deep sequencing and microarrays},
journal = {Molecular Reproduction and Development},
year = {2011},
volume = {78},
pages = {651--664},
number = {9},
abstract = {While most assisted reproductive technologies (ART) are considered
routine for the reproduction of species of economical importance,
such as the bovine, the impact of these manipulations on the developing
embryo remains largely unknown. In an effort to obtain a comprehensive
survey of the bovine embryo transcriptome and how it is modified
by ART, resources were combined to design an embryo-specific microarray.
Close to one million high-quality reads were produced from subtracted
bovine embryo libraries using Roche 454 Titanium deep sequencing
technology, which enabled the creation of an augmented bovine genome
catalog. This catalog was enriched with bovine embryo transcripts,
and included newly discovered indel type and 3′UTR variants. Using
this augmented bovine genome catalog, the EmbryoGENE Bovine Microarray
was designed and is composed of a total of 42,242 probes, including
21,139 known reference genes; 9,322 probes for novel transcribed
regions (NTRs); 3,677 alternatively spliced exons; 3,353 3′-tiling
probes; and 3,723 controls. A suite of bioinformatics tools was also
developed to facilitate microrarray data analysis and database creation;
it includes a quality control module, a Laboratory Information Management
System (LIMS) and microarray analysis software. Results obtained
during this study have already led to the identification of differentially
expressed blastocyst targets, NTRs, splice variants of the indel
type, and 3′UTR variants. We were able to confirm microarray results
by real-time PCR, indicating that the EmbryoGENE bovine microarray
has the power to detect physiologically relevant changes in gene
expression. Mol. Reprod. Dev. 78:651–664, 2011. © 2011 Wiley-Liss,
Inc.},
doi = {10.1002/mrd.21364},
issn = {1098-2795},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mrd.21364}
}
@ARTICLE{Roberts2010,
author = {Roberts, Andrew and Gumienny, Tina and Gleason, Ryan and Wang, Huang
and Padgett, Richard},
title = {Regulation of genes affecting body size and innate immunity by the
DBL-1/BMP-like pathway in Caenorhabditis elegans},
journal = {BMC Developmental Biology},
year = {2010},
volume = {10},
pages = {61},
number = {1},
abstract = {BACKGROUND:Bone morphogenetic proteins (BMPs) are members of the conserved
transforming growth factor ß (TGFß superfamily, and play many developmental
and homeostatic roles. In C. elegans, a BMP-like pathway, the DBL-1
pathway, controls body size and is involved in innate immunity. How
these functions are carried out, though, and what most of the downstream
targets of this pathway are, remain unknown.RESULTS:We performed
a microarray analysis and compared expression profiles of animals
lacking the SMA-6 DBL-1 receptor, which decreases pathway signaling,
with animals that overexpress DBL-1 ligand, which increases pathway
signaling. Consistent with a role for DBL-1 in control of body size,
we find positive regulation by DBL-1 of genes involved in physical
structure, protein synthesis and degradation, and metabolism. However,
cell cycle genes were mostly absent from our results. We also identified
genes in a hedgehog-related pathway, which may comprise a secondary
signaling pathway downstream of DBL-1 that controls body size. In
addition, DBL-1 signaling up-regulates pro-innate immunity genes.
We identified a reporter for DBL-1 signaling, which is normally repressed
but is up-regulated when DBL-1 signaling is reduced.CONCLUSIONS:Our
results indicate that body size in C. elegans is controlled in part
by regulation of metabolic processes as well as protein synthesis
and degradation. This supports the growing body of evidence that
suggests cell size is linked to metabolism. Furthermore, this study
discovered a possible role for hedgehog-related pathways in transmitting
the BMP-like signal from the hypodermis, where the core DBL-1 pathway
components are required, to other tissues in the animal. We also
identified the up-regulation of genes involved in innate immunity,
clarifying the role of DBL-1 in innate immunity. One of the highly
regulated genes is expressed at very low levels in wild-type animals,
but is strongly up-regulated in Sma/Mab mutants, making it a useful
reporter for DBL-1/BMP-like signaling in C. elegans.},
doi = {10.1186/1471-213X-10-61},
issn = {1471-213X},
pubmedid = {20529267},
url = {http://www.biomedcentral.com/1471-213X/10/61}
}
@ARTICLE{Roberts2008,
author = {Roberts, E. S. and Thomas, R. S. and Dorman, D. C.},
title = {Gene Expression Changes Following Acute Hydrogen Sulfide (H2S)-induced
Nasal Respiratory Epithelial Injury},
journal = {Toxicol Pathol},
year = {2008},
volume = {36},
pages = {560--567},
number = {4},
month = jun,
abstract = {Hydrogen sulfide (H2S) is a naturally occurring gas that is also associated
with several industries. The potential for widespread human inhalation
exposure to this toxic gas is a public health concern. The nasal
epithelium is especially susceptible to H2S-induced pathology. Injury
to and regeneration of the nasal respiratory mucosa occurred in animals
with ongoing H2S exposure, suggesting that the regenerated respiratory
epithelium under-goes an adaptive response and becomes resistant
to further injury. To better understand this response, ten-week-old
male Sprague-Dawley rats were exposed nose-only to either air or
200 ppm H2S for three hours per day for one day or five consecutive
days. Nasal respiratory epithelial cells at the site of injury and
regeneration were laser capture microdissected, and gene expression
profiles were generated at three, six, and twenty-four hours after
the initial three-hour exposure and at twenty-four hours after the
fifth exposure using the Affymetrix Rat Genome 230 2.0 microarray.
Gene ontology enrichment analysis showed that H2S exposure altered
gene expression associated with a variety of biological processes,
including cell cycle regulation, protein kinase regulation, and cytoskeletal
organization and biogenesis. Surprisingly, our results did not show
a significant change in cytochrome oxidase gene expression or bioenergetics.},
url = {http://tpx.sagepub.com/cgi/content/abstract/36/4/560}
}
@ARTICLE{Roberts2009,
author = {Roberts, Lisa and Bowers, Jessica and Sensinger, Kelly and Lisowski,
Andrew and Getts, Robert and Anderson, Mark G.},
title = {Identification of methods for use of formalin-fixed, paraffin-embedded
tissue samples in RNA expression profiling},
journal = {Genomics},
year = {2009},
volume = {94},
pages = {341--348},
number = {5},
month = nov,
abstract = {Formalin-fixed paraffin-embedded (FFPE) tissue samples are a potentially
valuable resource of expression information for medical research,
but are under-utilized due to degradation and modification of the
RNA. Using a random primer-based RNA amplification strategy, we have
evaluated multiple protocols for the extraction and isolation of
RNA from FFPE samples. We found that the RecoverAll RNA isolation
procedure with three or four slices (ten-microns in thickness), supplemented
with additional DNAse, gave optimal results. RNA integrity as assessed
by Agilent Bioanalyzer, and amplification of the 28S ribosomal RNA,
were predictive for the number of genes detected on Affymetrix arrays.
We obtained expression data for colon and lung tumor and normal FFPE
samples and matched frozen samples and found a high correlation between
frozen and matched FFPE samples (R2 between 0.82 and 0.89), while
the signature sets in tumor versus normal comparisons were also quite
similar. QPCR confirmed all 16 of the differential expression results
from the microarrays that we tested. Differentially expressed signature
genes from tumor versus matched normal FFPE tissue from colon and
lung were identified as cancer-related, with 95 colon tumor and 67
lung tumor genes identified, respectively.},
issn = {0888-7543},
keywords = {FFPE, Expression profiling, Microarrays, Colon cancer, Lung cancer,
RNA extraction, RampUP},
url = {http://www.sciencedirect.com/science/article/B6WG1-4WXHBT3-2/2/8914dab75e1150db23470b4f2ab946df}
}
@ARTICLE{Roberts2008a,
author = {Roberts, Peter C.},
title = {Gene expression microarray data analysis demystified},
journal = {Biotechnol Annu Rev},
year = {2008},
volume = {Volume 14},
pages = {29--61},
abstract = {The increasing use of gene expression microarrays, and depositing
of the resulting data into public repositories, means that more investigators
are interested in using the technology either directly or through
meta analysis of the publicly available data. The tools available
for data analysis have generally been developed for use by experts
in the field, making them difficult to use by the general research
community. For those interested in entering the field, especially
those without a background in statistics, it is difficult to understand
why experimental results can be so variable. The purpose of this
review is to go through the workflow of a typical microarray experiment,
to show that decisions made at each step, from choice of platform
through statistical analysis methods to biological interpretation,
are all sources of this variability.},
editor = {El-Gewely, M. Raafat},
issn = {1387-2656},
keywords = {microarray, microarray data analysis, gene expression, normalization,
preprocessing, statistical analysis, clustering, cross-platform comparison,
correction for multiple testing, pathway, gene ontology},
publisher = {Elsevier},
url = {http://www.sciencedirect.com/science/article/B7CTS-4SX89K0-7/2/fa2fe5d457d6141035b977f3f828d8a1}
}
@ARTICLE{Roberts2004,
author = {Roberts, Ruth A. and Michel, Cecile and Coyle, Beth and Freathy,
Caroline and Cain, Kelvin and Boitier, Eric},
title = {Regulation of apoptosis by peroxisome proliferators},
journal = {Toxicology Letters},
year = {2004},
volume = {149},
pages = {37--41},
number = {1-3},
month = apr,
abstract = {Peroxisome proliferators (PPs) constitute a large and chemically diverse
family of non-genotoxic rodent hepatocarcinogens that activate the
PP-activated receptor [alpha] (PPAR[alpha]). In order to investigate
the hypothesis that PPs elicit their carcinogenic effects through
the suppression of apoptosis, we established an in vitro assay for
apoptosis using both primary rat hepatocytes and the FaO rat hepatoma
cell line. Apoptosis was induced by transforming growth factor [beta]1
(TGF[beta]1), the physiological negative regulator of liver growth.
In this system, PPs could suppress both spontaneous and TGF[beta]1-induced
apoptosis. In order to understand the mechanisms of this regulation
of apoptosis, we conducted microarray analysis followed by pathway-specific
gene clustering in TGF[beta]1-treated cells. After treatment, 76
genes were up-regulated and 185 were down-regulated more than 1.5-fold.
Cluster analysis of up-regulated genes revealed three clusters, A-C.
Cluster A (4 h) was associated with 12% apoptosis and consisted of
genes mainly of the cytoskeleton and extracellular matrix such as
troponin and the proteoglycan SDC4. In cluster B (8 h; 25% apoptosis),
there were many pro- and anti-apoptotic genes such as XIAP, BAK1
and BAD, whereas at 16 h (40% apoptosis) the regulated genes were
mainly those of the cellular stress pathways such as the genes implicated
in the activation of the transcription factor NF[kappa]b. Genes found
down-regulated in response to TGF[beta]1 were mainly those associated
with oxidative stress and several genes implicated in glutathione
production and maintenance. Thus, TGF[beta]1 may induce apoptosis
via a down regulation of oxidant defence leading to the generation
of reactive oxygen species. The ability of PPs to impact on these
apoptosis pathways remains to be determined. To approach this question,
we have developed a technique using laser capture microdissection
of livers treated with the PP, clofibric acid coupled with gene expression
array analysis. Results show that some of the key steps of the LCM
process had an impact on the gene profiles generated. However, this
did not preclude accurate determination of a PP-specific molecular
signature. Thus, the choice of appropriate controls will ensure that
meaningful gene expression analyses can be performed on tissue microdissected
from the foci generated in clofibric acid treated livers. These data
will allow the identification of specific genes that are regulated
by PPs leading to changes in apoptosis and ultimately to tumours.},
booktitle = {Proceedings of EUROTOX 2003. The XLI European Congress of Toxicology.
Science for Safety},
issn = {0378-4274},
keywords = {Apoptosis, Peroxisome proliferators, TGF[beta]1, PPAR[alpha], Laser
capture microscopy, Genomics},
url = {http://www.sciencedirect.com/science/article/B6TCR-4BRPBRC-1/2/565560a84aafbc8c1f9aa868cc8e5a92}
}
@ARTICLE{Roberts2011,
author = {Roberts, R. Michael and Katayama, Mika and Magnuson, Scott R. and
Falduto, Michael T. and Torres, Karen E.O.},
title = {Transcript Profiling of Individual Twin Blastomeres Derived by Splitting
Two-Cell Stage Murine Embryos},
journal = {Biol Reprod},
year = {2011},
volume = {84},
pages = {487--494},
number = {3},
month = mar,
abstract = {In invertebrates and amphibians, informational macromolecules in egg
cytoplasm are organized to provide direction to the formation of
embryonic lineages, but it is unclear whether vestiges of such prepatterning
exist in mammals. Here we examined whether twin blastomeres from
2-cell stage mouse embryos differ in mRNA content. mRNA from 26 blastomeres
derived from 13 embryos approximately mid-way through their second
cell cycle was subjected to amplification. Twenty amplified samples
were hybridized to arrays. Of those samples that hybridized successfully,
12 samples in six pairs were used in the final analysis. Probes displaying
normalized values >0.25 (n = 4573) were examined for consistent bias
in expression within blastomere pairs. Although transcript content
varied between both individual embryos and twin blastomeres, no consistent
asymmetries were observed for the majority of genes, with only 178
genes displaying a >1.4-fold difference in expression across all
six pairs. Although class discovery clustering showed that blastomere
pairs separated into two distinct groups in terms of their differentially
expressed genes, when the data were tested for significance of asymmetrical
expression, only 39 genes with >1.4-fold change ratios in six of
six blastomere pairs passed the two-sample t-test (P < 0.05). Transcripts
encoding proteins implicated in RNA processing and cytoskeletal organization
were among the most abundant, differentially distributed mRNA, suggesting
that a stochastically based lack of synchrony in cell cycle progression
between the two cells might explain at least some and possibly all
of the asymmetries in transcript composition.},
comment = {10.1095/biolreprod.110.086884},
url = {http://www.biolreprod.org/cgi/content/abstract/84/3/487}
}
@ARTICLE{Robertson2009,
author = {Robertson, Laura S. and Iwanowicz, Luke R. and Marranca, Jamie Marie},
title = {Identification of centrarchid hepcidins and evidence that 17[beta]-estradiol
disrupts constitutive expression of hepcidin-1 and inducible expression
of hepcidin-2 in largemouth bass (Micropterus salmoides)},
journal = {Fish \& Shellfish Immunology},
year = {2009},
volume = {26},
pages = {898--907},
number = {6},
month = jun,
abstract = {Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory
hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in
largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus
dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site
in the amino-terminus that is missing in hepcidin-2, suggesting that
hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins
are predominately expressed in the liver of largemouth bass, similar
to other fish and mammals. Experimental exposure of pond-raised largemouth
bass to 17[beta]-estradiol and/or the bacteria Edwardsiella ictaluri
led to distinct changes in expression of hep-1 and hep-2. Estradiol
reduced the constitutive expression of hep-1 in the liver. Bacterial
exposure induced expression of hep-2, suggesting that hepcidin-2
may have an antimicrobial function, and this induction was abolished
by estradiol. To our knowledge, this is the first report of the regulation
of hepcidin expression by estradiol in either fish or mammals.},
issn = {1050-4648},
keywords = {Innate immunity, Antimicrobial peptide, Hepcidin, Fish, Largemouth
bass, Smallmouth bass, Estrogen, Estradiol, Real-time PCR},
url = {http://www.sciencedirect.com/science/article/B6WFN-4W38RH6-1/2/f18595109176c12fed8be47348e67e6b}
}
@ARTICLE{Robertson2007,
author = {Robertson, Nathan J. and Brook, Frances A. and Gardner, Richard L.
and Cobbold, Stephen P. and Waldmann, Herman and Fairchild, Paul
J.},
title = {Embryonic stem cell-derived tissues are immunogenic but their inherent
immune privilege promotes the induction of tolerance},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {20920--20925},
number = {52},
month = dec,
abstract = {Although human embryonic stem (ES) cells may one day provide a renewable
source of tissues for cell replacement therapy (CRT), histoincompatibility
remains a significant barrier to their clinical application. Current
estimates suggest that surprisingly few cell lines may be required
to facilitate rudimentary tissue matching. Nevertheless, the degree
of disparity between donor and recipient that may prove acceptable,
and the extent of matching that is therefore required, remain unknown.
To address this issue using a mouse model of CRT, we have derived
a panel of ES cell lines that differ from CBA/Ca recipients at defined
genetic loci. Here, we show that even expression of minor histocompatibility
(mH) antigens is sufficient to provoke acute rejection of tissues
differentiated from ES cells. Nevertheless, despite their immunogenicity
in vivo, transplantation tolerance may be readily established by
using minimal host conditioning with nondepleting monoclonal antibodies
specific for the T cell coreceptors, CD4 and CD8. This propensity
for tolerance could be attributed to the paucity of professional
antigen-presenting cells and the expression of transforming growth
factor (TGF)-{beta}2. Together, these factors contribute to a state
of acquired immune privilege that favors the polarization of infiltrating
T cells toward a regulatory phenotype. Although the natural privileged
status of ES cell-derived tissues is, therefore, insufficient to
overcome even mH barriers, our findings suggest it may be harnessed
effectively for the induction of dominant tolerance with minimal
therapeutic intervention.},
url = {http://www.pnas.org/cgi/content/abstract/104/52/20920}
}
@ARTICLE{Robins2005,
author = {Robins, Jared C. and Akeno, Nagako and Mukherjee, Aditi and Dalal,
Ravi R. and Aronow, Bruce J. and Koopman, Peter and Clemens, Thomas
L.},
title = {Hypoxia induces chondrocyte-specific gene expression in mesenchymal
cells in association with transcriptional activation of Sox9},
journal = {Bone},
year = {2005},
volume = {37},
pages = {313--322},
number = {3},
month = sep,
abstract = {Endochondral bone is formed during an avascular period in an environment
of low oxygen. Under these conditions, pluripotential mesenchymal
stromal cells preferentially differentiate into chondrocytes and
form cartilage. In this study, we investigated the hypothesis that
oxygen tension modulates bone mesenchymal cell fate by altering the
expression of genes that function to promote chondrogenesis. Microarray
of RNA samples from ST2 cells revealed significant changes in 728
array elements (P < 0.01) in response to hypoxia. Real-time PCR on
these RNA samples, and separate samples from C3H10T1/2 cells, revealed
hypoxia-induced changes in the expression of additional genes known
to be expressed by chondrocytes including Sox9 and its downstream
targets aggrecan and Col2a. These changes were accompanied by the
accumulation of mucopolysacharide as detected by alcian blue staining.
To investigate the mechanisms responsible for upregulation of Sox9
by hypoxia, we determined the effect of hypoxia on HIF-1[alpha] levels
and Sox9 promoter activity in ST2 cells. Hypoxia increased nuclear
accumulation of HIF-1[alpha] and activated the Sox9 promoter. The
ability of hypoxia to transactivate the Sox9 promoter was virtually
abolished by deletion of HIF-1[alpha] consensus sites within the
proximal promoter. These findings suggest that hypoxia promotes the
differentiation of mesenchymal cells along a chondrocyte pathway
in part by activating Sox-9 via a HIF-1[alpha]-dependent mechanism.},
issn = {8756-3282},
keywords = {Hypoxia, Mesenchymal cells, Sox9},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4GMJ98P-1/2/e523994316d931289bd672fae9441c96}
}
@ARTICLE{Robinson2009,
author = {Robinson, Jennilee B. and Telepnev, Maxim V. and Zudina, Irina V.
and Bouyer, Donald and Montenieri, John A. and Bearden, Scott W.
and Gage, Kenneth L. and Agar, Stacy L. and Foltz, Sheri M. and Chauhan,
Sadhana and Chopra, Ashok K. and Motin, Vladimir L.},
title = {Evaluation of a Yersinia pestis mutant impaired in a thermoregulated
type VI-like secretion system in flea, macrophage and murine models},
journal = {Microbial Pathogenesis},
year = {2009},
volume = {47},
pages = {243--251},
number = {5},
month = nov,
abstract = {Type VI secretion systems (T6SSs) have been identified recently in
several Gram-negative organisms and have been shown to be associated
with virulence in some bacterial pathogens. A T6SS of Yersinia pestis
CO92 (locus YPO0499-YPO0516) was deleted followed by investigation
of the phenotype of this mutation. We observed that this T6SS locus
of Y. pestis was preferentially expressed at 26 °C in comparison
to 37 °C suggesting a possible role in the flea cycle. However, we
found that the deletion of T6SS locus YPO0499-YPO0516 in Y. pestis
CO92 had no effect on the ability of this strain to infect the oriental
rat flea, Xenopsylla cheopis. Nevertheless, this mutant displayed
increased intracellular numbers in macrophage-like J774.A1 cells
after 20 h post-infection for bacterial cells pre-grown at 26 °C
indicating that expression of this T6SS locus limited intracellular
replication in macrophages. In addition, deletion of the YPO0499-YPO0516
locus reduced the uptake by macrophages of the Y. pestis mutant pre-grown
at 37 °C, suggesting that this T6SS locus has phagocytosis-promoting
activity. Further study of the virulence of the T6SS mutant in murine
bubonic and inhalation plague models revealed no attenuation in comparison
with the parental CO92 strain.},
issn = {0882-4010},
keywords = {Yersinia pestis, Type VI secretion system, Plague, Macrophage, Murine
model, Xenopsylla cheopis},
url = {http://www.sciencedirect.com/science/article/B6WN6-4X3DMVS-1/2/e73ef091fcb0542fd9f87b61841c1e48}
}
@ARTICLE{Robinson2010a,
author = {Robinson, Joshua F. and van Beelen, Vincent A. and Verhoef, Aart
and Renkens, Marc F. J. and Luijten, Mirjam and van Herwijnen, Marcel
H. M. and Westerman, Anja and Pennings, Jeroen L. A. and Piersma,
Aldert H.},
title = {Embryotoxicant-Specific Transcriptomic Responses in Rat Postimplantation
Whole-Embryo Culture},
journal = {Toxicol. Sci.},
year = {2010},
volume = {118},
pages = {675--685},
number = {2},
month = dec,
abstract = {Rat postimplantation whole-embryo culture (WEC) is a promising alternative
test for the assessment of developmental toxicity. Toxicogenomic-based
approaches may improve the predictive ability of the WEC model by
providing a means to identify compound-specific mechanistic responses
associated with embryotoxicity in vivo. Furthermore, alterations
in gene expression may serve as a sensitive, objective, and robust
marker, which precedes the observation of classical developmental
toxicity endpoints in time. In this study, in combination with morphological
developmental assessments, we studied transcriptomic responses associated
with four distinct teratogens (caffeine [CAF], methylmercury [MM],
monobutyl phthalate, and methoxyacetic acid) after 4 h of exposure,
well before apparent embryotoxicity in WEC. We evaluated gene expression
changes associated with similar levels of induced morphological embryotoxicity
for each teratogen (as determined by total morphological score),
evaluating for functional enrichment and quantitative changes in
response. Concentrations selected for each of the four teratogens
used induced a number of common effects on embryonic development
(neural tube closure and optic/otic system). Despite inducing common
morphological effects, our analysis suggests limited overlap in terms
of toxicogenomic response at the gene expression level and at the
level of biological processes across all four test chemicals. Many
unique responses associated with each chemical correlated with previously
hypothesized modes of developmental toxicity. For example, alterations
in developmental signaling and cholesterol metabolism were observed
with MM and CAF, respectively. This initial study suggests that distinct
chemically induced toxicogenomic responses precede morphological
effects in WEC and that these responses are relevant with mechanisms
of toxicity previously observed in vivo.},
comment = {10.1093/toxsci/kfq292},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/118/2/675}
}
@ARTICLE{Robinson2010,
author = {Robinson, Joshua F. and Griffith, William C. and Yu, Xiaozhong and
Hong, Sungwoo and Kim, Euvin and Faustman, Elaine M.},
title = {Methylmercury induced toxicogenomic response in C57 and SWV mouse
embryos undergoing neural tube closure},
journal = {Reproductive Toxicology},
year = {2010},
volume = {30},
pages = {284--291},
number = {2},
month = sep,
abstract = {Methylmercury (MeHg) is a developmental neurotoxicant and teratogen
and is hypothesized to perturb a wide range of biological processes,
like other metals including arsenic (As) and cadmium (Cd). Common
inbred mouse strains including C57 (sensitive) and SWV (resistant)
display differences in sensitivity to metals such as As and Cd when
exposed during neurulation. In this study, we investigated the impact
of MeHg on neurulation, assessing for potential differences in sensitivity
and associated toxicogenomic response in C57 and SWV mouse embryos.
Parallel with morphological assessments of neural tube closure, we
evaluated quantitative differences in MeHg-induced alterations in
expression between strains at the gene level and within gene-enriched
biological processes. Specifically, we observed differing sensitivities
to MeHg-induced impacts on neural tube closure between C57 and SWV
embryos in a time-dependent manner. These observations correlated
with greater impact on the expression of genes associated with development
and environmental stress-related pathways in the C57 compared to
the SWV. Additional developmental parameters (e.g. mortality, growth
effects) evaluated showed mixed significant effects across the two
strains and did not support observations of differential sensitivity
to MeHg. This study provides potential insights into MeHg-induced
mechanisms of developmental toxicity, alterations associated with
increased MeHg sensitivity and common biological processes affected
by metals in embryos undergoing neurulation.},
booktitle = {38th Annual Conference of the European Teratology Society},
issn = {0890-6238},
keywords = {Neurulation, Methylmercury, Toxicogenomics, SWV, Metals, Mouse},
url = {http://www.sciencedirect.com/science/article/B6TC0-5046M6M-3/2/b01c0eb9dcfab9858a943c15c598bcec}
}
@ARTICLE{Robinson2010b,
author = {Robinson, Joshua F. and Guerrette, Zachariah and Yu, Xiaozhong and
Hong, Sungwoo and Faustman, Elaine M.},
title = {A systems-based approach to investigate dose- and time-dependent
methylmercury-induced gene expression response in C57BL/6 mouse embryos
undergoing neurulation},
journal = {Birth Defects Research Part B: Developmental and Reproductive Toxicology},
year = {2010},
volume = {89},
pages = {188--200},
number = {3},
abstract = {Abstract 10.1002/bdrb.20241.abs BACKGROUND: Aberrations during neurulation
due to genetic and/or environmental factors underlie a variety of
adverse developmental outcomes, including neural tube defects (NTDs).
Methylmercury (MeHg) is a developmental neurotoxicant and teratogen
that perturbs a wide range of biological processes/pathways in animal
models, including those involved in early gestation (e.g., cell cycle,
cell differentiation). Yet, the relationship between these MeHg-linked
effects and changes in gestational development remains unresolved.
Specifically, current information lacks mechanistic comparisons across
dose or time for MeHg exposure during neurulation. These detailed
investigations are crucial for identifying sensitive indicators of
toxicity and for risk assessment applications. METHODS: Using a systems-based
toxicogenomic approach, we examined dose- and time-dependent effects
of MeHg on gene expression in C57BL/6 mouse embryos during cranial
neural tube closure, assessing for significantly altered genes and
associated Gene Ontology (GO) biological processes. Using the GO-based
application GO-Quant, we quantitatively assessed dose- and time-dependent
effects on gene expression within enriched GO biological processes
impacted by MeHg. RESULTS: We observed MeHg to significantly alter
expression of 883 genes, including several genes (e.g., Vangl2, Celsr1,
Ptk7, Twist, Tcf7) previously characterized to be crucial for neural
tube development. Significantly altered genes were associated with
development cell adhesion, cell cycle, and cell differentiation–related
GO biological processes. CONCLUSIONS: Our results suggest that MeHg-induced
impacts within these biological processes during gestational development
may underlie MeHg-induced teratogenic and neurodevelopmental toxicity
outcomes. Birth Defects Res (Part B) 89:188–200, 2010. © 2010
Wiley-Liss, Inc.},
issn = {1542-9741},
keywords = {metals, gene expression, methylmercury, development, neurulation,
neural tube defects, cell cycle, toxicogenomics},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bdrb.20241}
}
@ARTICLE{Robinson2009a,
author = {Robinson, Joshua F. and Yu, Xiaozhong and Hong, Sungwoo and Griffith,
William C. and Beyer, Richard and Kim, Euvin and Faustman, Elaine
M.},
title = {Cadmium-Induced Differential Toxicogenomic Response in Resistant
and Sensitive Mouse Strains Undergoing Neurulation},
journal = {Toxicol. Sci.},
year = {2009},
volume = {107},
pages = {206--219},
number = {1},
month = jan,
abstract = {Common inbred mouse strains, such as the C57BL/6 (C57) and the SWV,
display differences in sensitivity to environmental teratogens during
gestation. For example, the C57 is more sensitive than the SWV to
cadmium (Cd) exposure during neurulation, inducing a higher incidence
of neural tube defects (NTDs). Here, we report, using Cd as a model
teratogen, the first large scale toxicogenomic study to compare teratogen-induced
gene expression alterations in C57 and SWV embryos undergoing neurulation,
identifying toxicogenomic responses that associate with developmental
toxicity and differential sensitivity. Using a systems-based toxicogenomic
approach, comparing Cd-exposed and control C57 and SWV embryos (12-
and 24-h postinjection [p.i.] [gestational day 8.0, ip]), we examined
differentially expressed genes at multiple levels (biological process,
pathway, gene) using Gene Ontology (GO) analysis, pathway mapping
and cross-scatter plots. In both C57 and SWV embryos, we observed
several gene expression alterations linked with cell cycle-related
classifications, however, only in the C57 we observed upregulation
of p53-dependent mediators Ccng1 and Pmaip1, previously associated
with cell cycle arrest, apoptosis and NTD formation. In addition,
we also identified a greater reduction in expression of nervous system
development-related genes (e.g., Zic1, En2, Neurog1, Elavl4, Metrn,
Nr2f1, Nr2f2) in the C57 compared to the SWV (12-h p.i.). In summary,
our results indicate that differences in Cd-induced gene expression
profiles between NTD resistant and sensitive strains within enriched
biological processes (including developmental and cell cycle-related
categories) associate with increased sensitivity to developmental
toxicity as determined by observations of increased NTD formation,
mortality (resorptions) and reduced fetal growth. Such observations
may provide more detailed and useful mechanistic clues for identification
of differences in life-stage specific teratogenic response.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/107/1/206}
}
@ARTICLE{Robinson2011,
author = {Joshua F. Robinson and Xiaozhong Yu and Estefania G. Moreira and
Sungwoo Hong and Elaine M. Faustman},
title = {Arsenic- and cadmium-induced toxicogenomic response in mouse embryos
undergoing neurulation},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {250},
pages = {117 - 129},
number = {2},
abstract = {Arsenic (As) and cadmium (Cd) are well-characterized teratogens in
animal models inducing embryotoxicity and neural tube defects (NTDs)
when exposed during neurulation. Toxicological research is needed
to resolve the specific biological processes and associated molecular
pathways underlying metal-induced toxicity during this timeframe
in gestational development. In this study, we investigated the dose-dependent
effects of As and Cd on gene expression in C57BL/6J mouse embryos
exposed in utero during neurulation (GD8) to identify significantly
altered genes and corresponding biological processes associated with
embryotoxicity. We quantitatively examined the toxicogenomic dose–response
relationship at the gene level. Our results suggest that As and Cd
induce dose-dependent gene expression alterations representing shared
(cell cycle, response to UV, glutathione metabolism, RNA processing)
and unique (alcohol/sugar metabolism) biological processes, which
serve as robust indicators of metal-induced developmental toxicity
and indicate underlying embryotoxic effects. Our observations also
correlate well with previously identified impacts of As and Cd on
specific genes associated with metal-induced toxicity (Cdkn1a, Mt1).
In summary, we have identified in a quantitative manner As and Cd
induced dose-dependent effects on gene expression in mouse embryos
during a peak window of sensitivity to embryotoxicity and NTDs in
the sensitive C57BL/6J strain.},
doi = {10.1016/j.taap.2010.09.018},
issn = {0041-008X},
keywords = {Arsenic},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X10003601}
}
@ARTICLE{Robinzon2009,
author = {Robinzon, Shahar and Dafa-Berger, Avis and Dyer, Mathew D. and Paeper,
Bryan and Proll, Sean C. and Teal, Thomas H. and Rom, Slava and Fishman,
Daniel and Rager-Zisman, Bracha and Katze, Michael G.},
title = {Impaired Cholesterol Biosynthesis in a Neuronal Cell Line Persistently
Infected with Measles Virus},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {5495--5504},
number = {11},
month = jun,
abstract = {Measles virus remains a substantial cause of morbidity and mortality,
producing acute infection with a potential for development of viral
persistence. To study the events underlying acute and persistent
measles virus infection, we performed a global transcriptional analysis
on murine neuroblastoma cells that were acutely or persistently infected
with measles virus. In general, we found that acute infection induced
significantly more gene expression changes than did persistent infection.
A functional enrichment analysis to identify which host pathways
were perturbed during each of these infections identified several
pathways related to cholesterol biosynthesis, including cholesterol
metabolic processes, hydroxymethylglutaryl-coenzyme A (CoA) reductase
activity, and acetyl-CoA C-acetyltransferase activity. We also found
that measles virus colocalized to lipid rafts in both acute and persistent
infection models and that the majority of genes associated with cholesterol
synthesis were downregulated in persistent infection relative to
acute infection, suggesting a possible link with the defective viral
budding in persistent infection. Further, we found that pharmacological
inhibition of cholesterol synthesis resulted in the inhibition of
viral budding during acute infection. In summary, persistent measles
viral infection was associated with decreased cholesterol synthesis,
a lower abundance of cholesterol and lipid rafts in the cell membrane,
and inhibition of giant-cell formation and release of viral progeny.},
url = {http://jvi.asm.org/cgi/content/abstract/83/11/5495}
}
@ARTICLE{Robischon2011,
author = {Robischon, Marcel and Du, Juan and Miura, Eriko and Groover, Andrew},
title = {The Populus Class III HD ZIP, popREVOLUTA, Influences Cambium Initiation
and Patterning of Woody Stems},
journal = {Plant Physiology},
year = {2011},
volume = {155},
pages = {1214--1225},
number = {3},
month = mar,
abstract = {The secondary growth of a woody stem requires the formation of a vascular
cambium at an appropriate position and proper patterning of the vascular
tissues derived from the cambium. Class III homeodomain-leucine zipper
(HD ZIP) transcription factors have been implicated in polarity determination
and patterning in lateral organs and primary vascular tissues and
in the initiation and function of shoot apical meristems. We report
here the functional characterization of a Populus class III HD ZIP
gene, popREVOLUTA (PRE), that demonstrates another role for class
III HD ZIPs in regulating the development of cambia and secondary
vascular tissues. PRE is orthologous to Arabidopsis (Arabidopsis
thaliana) REVOLUTA and is expressed in both the shoot apical meristem
and in the cambial zone and secondary vascular tissues. Transgenic
Populus expressing a microRNA-resistant form of PRE presents unstable
phenotypic abnormalities affecting both primary and secondary growth.
Surprisingly, phenotypic changes include abnormal formation of cambia
within cortical parenchyma that can produce secondary vascular tissues
in reverse polarity. Genes misexpressed in PRE mutants include transcription
factors and auxin-related genes previously implicated in class III
HD ZIP functions during primary growth. Together, these results suggest
that PRE plays a fundamental role in the initiation of the cambium
and in regulating the patterning of secondary vascular tissues.},
comment = {10.1104/pp.110.167007},
url = {http://www.plantphysiol.org/cgi/content/abstract/155/3/1214}
}
@ARTICLE{Robison2009,
author = {Robison, Elizabeth and Mondala, Tony and Williams, Adam and Head,
Steven and Salomon, Daniel and Kurian, Sunil},
title = {Whole genome transcript profiling from fingerstick blood samples:
a comparison and feasibility study},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {617},
number = {1},
abstract = {BACKGROUND:Whole genome gene expression profiling has revolutionized
research in the past decade especially with the advent of microarrays.
Recently, there have been significant improvements in whole blood
RNA isolation techniques which, through stabilization of RNA at the
time of sample collection, avoid bias and artifacts introduced during
sample handling. Despite these improvements, current human whole
blood RNA stabilization/isolation kits are limited by the requirement
of a venous blood sample of at least 2.5 mL. While fingerstick blood
collection has been used for many different assays, there has yet
to be a kit developed to isolate high quality RNA for use in gene
expression studies from such small human samples. The clinical and
field testing advantages of obtaining reliable and reproducible gene
expression data from a fingerstick are many; it is less invasive,
time saving, more mobile, and eliminates the need of a trained phlebotomist.
Furthermore, this method could also be employed in small animal studies,
i.e. mice, where larger sample collections often require sacrificing
the animal. In this study, we offer a rapid and simple method to
extract sufficient amounts of high quality total RNA from approximately
70 µl of whole blood collected via a fingerstick using a modified
protocol of the commercially available Qiagen PAXgene RNA Blood Kit.RESULTS:From
two sets of fingerstick collections, about 70 uL whole blood collected
via finger lancet and capillary tube, we recovered an average of
252.6 ng total RNA with an average RIN of 9.3. The post-amplification
yields for 50 ng of total RNA averaged at 7.0 ug cDNA. The cDNA hybridized
to Affymetrix HG-U133 Plus 2.0 GeneChips had an average % Present
call of 52.5%. Both fingerstick collections were highly correlated
with r2 values ranging from 0.94 to 0.97. Similarly both fingerstick
collections were highly correlated to the venous collection with
r2 values ranging from 0.88 to 0.96 for fingerstick collection 1
and 0.94 to 0.96 for fingerstick collection 2.CONCLUSIONS:Our comparisons
of RNA quality and gene expression data of the fingerstick method
with traditionally processed sample workflows demonstrate excellent
RNA quality from the capillary collection as well as very high correlations
of gene expression data.},
doi = {10.1186/1471-2164-10-617},
issn = {1471-2164},
pubmedid = {20017944},
url = {http://www.biomedcentral.com/1471-2164/10/617}
}
@ARTICLE{Roccaro2009,
author = {Roccaro, Aldo M. and Sacco, Antonio and Chen, Changzhong and Runnels,
Judith and Leleu, Xavier and Azab, Feda and Azab, Abdel Kareem and
Jia, Xiaoying and Ngo, Hai T. and Melhem, Molly R. and Burwick, Nicholas
and Varticovski, Lyuba and Novina, Carl D. and Rollins, Barrett J.
and Anderson, Kenneth C. and Ghobrial, Irene M.},
title = {microRNA expression in the biology, prognosis, and therapy of Waldenstrom
macroglobulinemia},
journal = {Blood},
year = {2009},
volume = {113},
pages = {4391--4402},
number = {18},
month = apr,
abstract = {Multilevel genetic characterization of Waldenstrom macroglobulinemia
(WM) is required to improve our understanding of the underlying molecular
changes that lead to the initiation and progression of this disease.
We performed microRNA-expression profiling of bone marrow-derived
CD19+ WM cells, compared with their normal cellular counterparts
and validated data by quantitative reverse-transcription-polymerase
chain reaction (qRT-PCR). We identified a WM-specific microRNA signature
characterized by increased expression of microRNA-363*/-206/-494/-155/-184/-542-3p,
and decreased expression of microRNA-9* (ANOVA; P < .01). We found
that microRNA-155 regulates proliferation and growth of WM cells
in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-{kappa}B
pathways. Potential microRNA-155 target genes were identified using
gene-expression profiling and included genes involved in cell-cycle
progression, adhesion, and migration. Importantly, increased expression
of the 6 miRNAs significantly correlated with a poorer outcome predicted
by the International Prognostic Staging System for WM. We further
demonstrated that therapeutic agents commonly used in WM alter the
levels of the major miRNAs identified, by inducing downmodulation
of 5 increased miRNAs and up-modulation of patient-downexpressed
miRNA-9*. These data indicate that microRNAs play a pivotal role
in the biology of WM; represent important prognostic marker; and
provide the basis for the development of new microRNA-based targeted
therapies in WM.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/18/4391}
}
@ARTICLE{Roccaro2010a,
author = {Roccaro, Aldo M. and Sacco, Antonio and Husu, Emanuel N. and Pitsillides,
Costas and Vesole, Steven and Azab, Abdel Kareem and Azab, Feda and
Melhem, Molly and Ngo, Hai T. and Quang, Phong and Maiso, Patricia
and Runnels, Judith and Liang, Mei-Chih and Wong, Kwok-Kin and Lin,
Charles and Ghobrial, Irene M.},
title = {Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy
in Waldenstrom macroglobulinemia},
journal = {Blood},
year = {2010},
volume = {115},
pages = {559--569},
number = {3},
month = jan,
abstract = {We have previously shown clinical activity of a mammalian target of
rapamycin (mTOR) complex 1 inhibitor in Waldenstrom macroglobulinemia
(WM). However, 50% of patients did not respond to therapy. We therefore
examined mechanisms of activation of the phosphoinositide 3-kinase
(PI3K)/Akt/mTOR in WM, and mechanisms of overcoming resistance to
therapy. We first demonstrated that primary WM cells show constitutive
activation of the PI3K/Akt pathway, supported by decreased expression
of phosphate and tensin homolog tumor suppressor gene (PTEN) at the
gene and protein levels, together with constitutive activation of
Akt and mTOR. We illustrated that dual targeting of the PI3K/mTOR
pathway by the novel inhibitor NVP-BEZ235 showed higher cytotoxicity
on WM cells compared with inhibition of the PI3K or mTOR pathways
alone. In addition, NVP-BEZ235 inhibited both rictor and raptor,
thus abrogating the rictor-induced Akt phosphorylation. NVP-BEZ235
also induced significant cytotoxicity in WM cells in a caspase-dependent
and -independent manner, through targeting the Forkhead box transcription
factors. In addition, NVP-BEZ235 targeted WM cells in the context
of bone marrow microenvironment, leading to significant inhibition
of migration, adhesion in vitro, and homing in vivo. These studies
therefore show that dual targeting of the PI3K/mTOR pathway is a
better modality of targeted therapy for tumors that harbor activation
of the PI3K/mTOR signaling cascade, such as WM.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/3/559}
}
@ARTICLE{Roccaro2010,
author = {Roccaro, Aldo M. and Sacco, Antonio and Jia, Xiaoying and Azab, Abdel
Kareem and Maiso, Patricia and Ngo, Hai T. and Azab, Feda and Runnels,
Judith and Quang, Phong and Ghobrial, Irene M.},
title = {microRNA-dependent modulation of histone acetylation in Waldenstrom
macroglobulinemia},
journal = {Blood},
year = {2010},
volume = {116},
pages = {1506--1514},
number = {9},
month = sep,
abstract = {Waldenstrom macroglobulinemia (WM) cells present with increased expression
of microRNA-206 (miRNA-206) and reduced expression of miRNA-9*. Predicted
miRNA-206- and -9*-targeted genes include histone deacetylases (HDACs)
and histone acetyl transferases (HATs), indicating that these miRNAs
may play a role in regulating histone acetylation. We were able to
demonstrate that primary WM cells are characterized by unbalanced
expression of HDACs and HATs, responsible for decreased acetylated
histone-H3 and -H4, and increased HDAC activity. We next examined
whether miRNA-206 and -9* modulate the aberrant expression of HDAC
and HATs in WM cells leading to increased transcriptional activity.
We found that restoring miRNA-9* levels induced toxicity in WM cells,
supported by down-modulation of HDAC4 and HDAC5 and up-regulation
of acetyl-histone-H3 and -H4. These, together with inhibited HDAC
activity, led to induction of apoptosis and autophagy in WM cells.
To further confirm that miRNA-9*-dependent modulation of histone
acetylation is responsible for induction of WM cytotoxicity, a novel
class of HDAC inhibitor (LBH589) was used; we confirmed that inhibition
of HDAC activity leads to toxicity in this disease. These findings
confirm that histone-modifying genes and HDAC activity are deregulated
in WM cells, partially driven by the aberrant expression of miRNA-206
and -9* in the tumor clone.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/116/9/1506}
}
@ARTICLE{Roccaro2009a,
author = {Roccaro, Aldo M. and Sacco, Antonio and Thompson, Brian and Leleu,
Xavier and Azab, Abdel Kareem and Azab, Feda and Runnels, Judith
and Jia, Xiaoying and Ngo, Hai T. and Melhem, Molly R. and Lin, Charles
P. and Ribatti, Domenico and Rollins, Barrett J. and Witzig, Thomas
E. and Anderson, Kenneth C. and Ghobrial, Irene M.},
title = {MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma},
journal = {Blood},
year = {2009},
volume = {113},
pages = {6669--6680},
number = {26},
month = jun,
abstract = {Detailed genomic studies have shown that cytogenetic abnormalities
contribute to multiple myeloma (MM) pathogenesis and disease progression.
Nevertheless, little is known about the characteristics of MM at
the epigenetic level and specifically how microRNAs regulate MM progression
in the context of the bone marrow milieu. Therefore, we performed
microRNA expression profiling of bone marrow derived CD138+ MM cells
versus their normal cellular counterparts and validated data by qRT-PCR.
We identified a MM-specific microRNA signature characterized by down-expression
of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b
(P < .01). We investigated the functional role of microRNA-15a and
-16 and showed that they regulate proliferation and growth of MM
cells in vitro and in vivo by inhibiting AKT serine/threonine-protein-kinase
(AKT3), ribosomal-protein-S6, MAP-kinases, and NF-{kappa}B-activator
MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity
even in the context of the bone marrow milieu in vitro and in vivo.
These data indicate that microRNAs play a pivotal role in the biology
of MM and represent important targets for novel therapies in MM.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/26/6669}
}
@ARTICLE{Rocchi2005,
author = {Rocchi, Palma and Beraldi, Eliana and Ettinger, Susan and Fazli,
Ladan and Vessella, Robert L. and Nelson, Colleen and Gleave, Martin},
title = {Increased Hsp27 after Androgen Ablation Facilitates Androgen-Independent
Progression in Prostate Cancer via Signal Transducers and Activators
of Transcription 3-Mediated Suppression of Apoptosis},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {11083--11093},
number = {23},
month = dec,
abstract = {One strategy to improve therapies in prostate cancer involves targeting
cytoprotective genes activated by androgen withdrawal to delay the
emergence of the androgen-independent (AI) phenotype. The objectives
of this study were to define changes in Hsp27 levels after androgen
ablation and to evaluate the functional relevance of these changes
in AI progression. Using a tissue microarray of 232 specimens of
hormone-naive and post-hormone ablation-treated prostate cancer,
we found that Hsp27 levels increase after androgen ablation to become
highly expressed (>4-fold, P [≤] 0.01) in AI tumors. Hsp27 overexpression
rendered LNCaP cells highly resistant to androgen withdrawal both
in vitro and in vivo. Tumor volume and serum prostate-specific antigen
levels increased 4.3- and 10-fold faster after castration when Hsp27
was overexpressed. Treatment of LNCaP tumor cells in vitro with Hsp27
antisense oligonucleotides (ASO) or short-interfering RNA suppressed
Hsp27 levels in a dose-dependent and sequence-specific manner increased
the apoptotic sub-G0-G1 fraction and caspase-3 cleavage >2-fold,
as well as decreased signal transducers and activators of transcription
3 (Stat3) levels and its downstream genes, c-fos and sPLA-2. The
cytoprotection afforded by Hsp27 overexpression was attenuated by
Stat3 knockdown using specific Stat3 ASO. Coimmunoprecipitation and
immunofluorescence confirmed that Hsp27 interacts with Stat3 and
that Stat3 levels correlated directly with Hsp27 levels. Hsp27 ASO
treatment in athymic mice bearing LNCaP tumors significantly delayed
LNCaP tumor growth after castration, decreasing mean tumor volume
and serum prostate-specific antigen levels by 57% and 69%, respectively.
These findings identify Hsp27 as a modulator of Stat3-regulated apoptosis
after androgen ablation and as a potential therapeutic target in
advanced prostate cancer.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/23/11083}
}
@ARTICLE{Rocha2010,
author = {Rocha, J. C. and Chaves, C. B. and Leite, V. P. and Moreira, F. C.
and Ramalho, D. M.},
title = {Impact of microsatellite instability in overall survival of women
with endometrial cancer.},
journal = {ASCO Meeting Abstracts},
year = {2010},
volume = {28},
pages = {5025--},
number = {15_suppl},
month = may,
abstract = {5025 Background: Genetic alterations in DNA mismatch repair (MMR)
genes cause microsatellite instability (MSI). MSI is a primary feature
of HNPCC; in some sporadic tumors it is result of the silencing of
MMR genes by methylation. Although a number of studies have correlated
MSI with better outcomes in colon cancer, the impact of MSI in endometrial
adenocarcinoma (EC) has been poorly explored. In this study, we assessed
the relevance of MSI status in overall survival (OS) of pts with
the diagnosis of EC from 2000 to 2003 in a single institution. Methods:
A total of 395 pts were selected; out of these, 231 pts were considered
eligible for the study after histologic review, and tissue blocks
recovery. DNA was extracted from paraffin embedded tumor and normal
tissue and six different microsatellite regions (BAT-25, BAT-26,
D2S123, D5S346, D17S250 and BAT-40) were amplified by PCR. PCR product
sizing and MSI identification was performed using the Agilent 2100
Bioanalyzer platform. Tumors were classified as MSS when all markers
were stable, as MSI-L when only one marker was unstable, and as MSI-H
when at least two markers were unstable. Results: The median age
was 64 (25-90yo). PCR and MSI analysis were successful in 97.4% of
the cases; 186 out of 225 tumors, were classified as type I (82.7%),
32 tumors were type II (14.2%), and 7 were inconclusive and classified
as others. According to FIGO staging criteria, 137 pts (60.9%) were
stage I; 47 (20.9%) stage II; 36 (16%) stage III; 5 (2.2%) stage
IV. MSI was found in 75 pts (32.5%). Among those with type I subtype,
MSI was presented in 64 pts (34.4%) and in 32 pts with type II (14.2%).
No significant difference in OS was found between MSI-L and MSI-H
after Fisher's Exact Test, therefore tumors with any MSI status were
joined for further comparisons. FIGO lower stages (p = 0.006), type
I subtype (p = 0.032), and MSI (p = 0.007) were prognostic for longer
OS (univariable analysis). Cox regression was used for multivariable
analysis, and MSI status sustained significant after adjustment for
other variables (p = 0.013). Conclusions: MSI was an independent
prognostic factor for EC in this retrospective study. Together with
other relevant characteristics could be used as a molecular marker
for the prediction of OS. No significant financial relationships
to disclose.},
url = {http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/5025}
}
@ARTICLE{Rocha-Sanchez2007,
author = {Rocha-Sanchez, Sonia M.S. and Morris, Kenneth A. and Kachar, Bechara
and Nichols, David and Fritzsch, Bernd and Beisel, Kirk W.},
title = {Developmental expression of Kcnq4 in vestibular neurons and neurosensory
epithelia},
journal = {Brain Research},
year = {2007},
volume = {1139},
pages = {117--125},
month = mar,
abstract = {Sensory signal transduction of the inner ear afferent neurons and
hair cells (HCs) requires numerous ionic conductances. The KCNQ4
voltage-gated M-type potassium channel is thought to set the resting
membrane potential in cochlear HCs. Here we describe the spatiotemporal
expression patterns of Kcnq4 and the associated alternative splice
forms in the HCs of vestibular labyrinth. Whole mount immunodetection,
qualitative and quantitative RT-PCR were performed to characterize
the expression patterns of Kcnq4 transcripts and proteins. A topographical
expression and upregulation of Kcnq4 during development was observed
and indicated that Kcnq4 is not restricted to either a specific vestibular
structure or cell type, but is present in afferent calyxes, vestibular
ganglion neurons, and both type I and type II HCs. Of the four alternative
splice variants, Kcnq4_v1 transcripts were the predominant form in
the HCs, while Kcnq4_v3 was the major variant in the vestibular neurons.
Differential quantitative expression of Kcnq4_v1 and Kcnq4_v3 were
respectively detected in the striolar and extra-striolar regions
of the utricle and saccule. Analysis of gerbils and rats yielded
results similar to those obtained in mice, suggesting that the spatiotemporal
expression pattern of Kcnq4 in the vestibular system is conserved
among rodents. Analyses of vestibular HCs of Bdnf conditional mutant
mice, which are devoid of any innervation, demonstrate that regulation
of Kcnq4 expression in vestibular HCs is independent of innervation.},
issn = {0006-8993},
keywords = {Vestibular hair cell, Ion channel, Kcnq4, Alternative splice variant,
Immunohistochemistry, Immunofluorescence, In situ hybridization,
RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6SYR-4MS9RH5-3/2/2d3358b95b458de58d674a303558c1c7}
}
@ARTICLE{Rocha-Sanchez2011,
author = {Rocha-Sanchez, Sonia M. and Scheetz, Laura R. and Contreras, Melissa
and Weston, Michael D. and Korte, Megan and McGee, JoAnn and Walsh,
Edward J.},
title = {Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair
Cells and Supporting Cells},
journal = {J. Neurosci.},
year = {2011},
volume = {31},
pages = {8883-8893},
number = {24},
abstract = {Adult mammalian auditory hair cells (HCs) and their associated supporting
cells (SCs) do not proliferate, and HC death leads to irreversible
neurosensory hearing loss and balance impairment. In nonmammalian
vertebrates, loss of HCs induces mitotic proliferation of adjacent
nonsensory SCs and/or direct SC transdifferentiation to generate
replacement cells. This results in the structural and functional
recovery of the nonmammalian sensory systems. Potential replacement
of mammalian auditory HCs, either by transplanting cells or by transforming
existing cells through molecular therapy, has long been proposed.
However, HC replacement strategies with clear therapeutic potential
remain elusive. The retinoblastoma (pRB) family of cell cycle regulators,
Rb1, Rbl1 (p107), and Rbl2 (p130), regulate the G1- to S-phase transition
in proliferating cells. In the inner ear, the biochemical and molecular
pathways involving pRBs, particularly p107 and p130, are relatively
unexplored and their therapeutic suitability is yet to be determined.
In this study, we analyzed the cochleae of adult p130 knock-out (p130-/-)
mice and showed that lack of the p130 gene results in extra rows
of HCs and SCs in the more apical regions of the cochlea. No evidence
of transdifferentiation of these supernumerary SCs into HCs was observed
in the p130-/- mouse. Nevertheless, unscheduled proliferation of
SCs in the adult p130-/- cochlea coupled to downregulation of bona
fide cell cycle inhibitors provides a mechanistic basis for the role
of p130 as a regulator of SC and HC mitotic quiescence in the more
apical regions of the cochlea. Interestingly, p130-/- mice exhibited
nearly normal peripheral auditory sensitivity.},
doi = {10.1523/JNEUROSCI.5821-10.2011},
eprint = {http://www.jneurosci.org/cgi/reprint/31/24/8883.pdf},
url = {http://www.jneurosci.org/cgi/content/abstract/31/24/8883}
}
@ARTICLE{Rochester2007,
author = {Rochester, Mark A. and Patel, Nilay and Turney, Benjamin W. and Davies,
David R. and Roberts, Ian S. and Crew, Jeremy and Protheroe, Andrew
and Macaulay, Valentine M.},
title = {The type 1 insulin-like growth factor receptor is over-expressed
in bladder cancer},
journal = {BJU International},
year = {2007},
volume = {100},
pages = {1396--1401},
number = {6},
abstract = {OBJECTIVE To analyse bladder cancer biopsies and investigate the pattern
of expression of the type 1 insulin-like growth factor receptor (IGF1R),
a receptor tyrosine kinase that mediates tumour cell proliferation,
motility and protection from apoptosis. MATERIALS AND METHODS Formalin-fixed
specimens of bladder cancer (40 whole-mount, 80 cores on a tumour
microarray) and normal bladder (15 samples) were stained immunohistochemically
for the IGF1R. The IGF1R expression was also measured by quantitative
reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA
extracted from fresh frozen bladder cancers (61) and benign bladder
(12). RESULTS Of the 15 samples of normal bladder, 14 showed negligible
(1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+)
or heavy (4+) staining for IGF1R was detected in 89 (74%) of the
120 samples of malignant urothelium. Q-RT-PCR showed significantly
higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta–T4)
than in normal bladder (PÂ <Â 0.05), indicating up-regulation at
the transcriptional level. This difference was particularly evident
when comparing normal urothelium with superficial (Ta–T1) or invasive
(T2–4) tumours; only the latter showed significant IGF1R over-expression
at the RNA level (PÂ <Â 0.05 vs normal bladder). CONCLUSION The IGF1R
is up-regulated in bladder cancer compared with non-malignant bladder,
and might contribute to a propensity for invasion.},
issn = {1464-410X},
keywords = {insulin-like growth factor, IGF receptor, bladder cancer, expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-410X.2007.06931.x}
}
@ARTICLE{Rochon2006,
author = {Rochon, Christelle and Frouin, Vincent and Bortoli, Sylvie and Giraud-Triboult,
Karine and Duverger, Valérie and Vaigot, Pierre and Petat, Cyrile
and Fouchet, Pierre and Lassalle, Bruno and Alibert, Olivier and
Gidrol, Xavier and Piétu, Geneviève},
title = {Comparison of gene expression pattern in SP cell populations from
four tissues to define common "stemness functions"},
journal = {Experimental Cell Research},
year = {2006},
volume = {312},
pages = {2074--2082},
number = {11},
month = jul,
abstract = {The goal of our study was to identify a subset of genes commonly expressed
in Side Populations (SP), isolated by Hoechst staining followed by
flow cytometry, from adult mouse bone marrow, male adult germinal
cells, muscle primary culture, and mesenchymal cells. These SP cells
have been proposed to be a "stem-like" population and are used here
as a "model" that may reveal mechanisms which would be relevant for
a better understanding of stem cell properties. Transcriptional profiles
for SP and the more differentiated non-SP cells isolated from the
four tissues were compared by hybridization on microarray using a
common external reference. Among the 503 genes differentially expressed,
which discriminate SP and non-SP cells in all the tissues, the genes
upregulated in SP cells are implicated in the quiescent status of
the cells, the maintenance of their pluripotency and the capacity
to undergo asymmetric division. These genes may be responsible for
the decision for self-renewal of these cells, whereas the repression
of lineage-affiliated genes in SP cells could be responsible for
their undifferentiated state. These genes, acting in concert, may
be the key players that mediate the mechanisms that control stem
cell functions, and our results suggest that we have identified common
"stemness functions" of these "stem-like" cells.},
issn = {0014-4827},
keywords = {SP cells, Microarray, Gene expression profiling},
url = {http://www.sciencedirect.com/science/article/B6WFC-4JS1N0V-7/2/8e3b86ede3de3d0b7890f724ed3f43d4}
}
@ARTICLE{Rock2007,
author = {Rock, Jason R. and Cecilia Lopez, M. and Baker, Henry V. and Harfe,
Brian D.},
title = {Identification of genes expressed in the mouse limb using a novel
ZPA microarray approach},
journal = {Gene Expression Patterns},
year = {2007},
volume = {8},
pages = {19--26},
number = {1},
month = dec,
abstract = {One well-studied signaling center in the developing vertebrate limb,
the zone of polarizing activity (ZPA), produces the morphogen sonic
hedgehog that is necessary for normal growth and pattern formation.
To identify additional factors expressed in the ZPA of the mouse
limb bud, the Shhgfpcre allele was used to purify ZPA cells using
fluorescence-activated cell sorting. Microarray technology was then
used to identify genes whose expression was elevated in the ZPA compared
to the rest of the limb. In situ hybridization confirmed the expression
of two known transcription factors, Hlxb9 and Tcfap2b, an uncharacterized
EST, and a transmembrane protein of unknown function in domains overlapping
the ZPA. The expression of two other genes was confirmed by rtPCR.
The methods described in this report will be applicable for identifying
genes enriched in Shh-expressing cells throughout development.},
issn = {1567-133X},
keywords = {ZPA, Shh, Tmem16a, Limb, Mouse, Microarray, Affymetrix, FACS, Tcfap2b,
Hlxb9, Ppp1cb, Ywhaz},
url = {http://www.sciencedirect.com/science/article/B6W8W-4PJV1G0-1/2/734ccc8c8e2cf77f8eafdbf77986379a}
}
@ARTICLE{Rock2009,
author = {Rock, Jason R. and O'Neal, Wanda K. and Gabriel, Sherif E. and Randell,
Scott H. and Harfe, Brian D. and Boucher, Richard C. and Grubb, Barbara
R.},
title = {Transmembrane Protein 16A (TMEM16A) Is a Ca2+-regulated Cl- Secretory
Channel in Mouse Airways},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {14875--14880},
number = {22},
month = may,
abstract = {For almost two decades, it has been postulated that calcium-activated
Cl- channels (CaCCs) play a role in airway epithelial Cl- secretion,
but until recently, the molecular identity of the airway CaCC(s)
was unknown. Recent studies have unequivocally identified TMEM16A
as a glandular epithelial CaCC. We have studied the airway bioelectrics
of neonatal mice homozygous for a null allele of Tmem16a (Tmem16a-/-)
to investigate the role of this channel in Cl- secretion in airway
surface epithelium. When compared with wild-type tracheas, the Tmem16a-/-
tracheas exhibited a >60% reduction in purinoceptor (UTP)-regulated
CaCC activity. Other members of the Tmem16 gene family, including
Tmem16f and Tmem16k, were also detected by reverse transcription-PCR
in neonatal tracheal epithelium, suggesting that other family members
could be considered as contributing to the small residual UTP response.
TMEM16A, however, appeared to contribute little to unstimulated Cl-
secretion, whereas studies with cystic fibrosis transmembrane conductance
regulator (CFTR)-deficient mice and wild-type littermates revealed
that unstimulated Cl- secretion reflected [~]50% CFTR activity and
[~]50% non-Tmem16a activity. Interestingly, the tracheas of both
the Tmem16a-/- and the CFTR-/- mice exhibited similar congenital
cartilaginous defects that may reflect a common Cl- secretory defect
mediated by the molecularly distinct Cl- channels. Importantly, the
residual CaCC activity in Tmem16a-/- mice appeared inadequate for
normal airway hydration because Tmem16a-/- tracheas exhibited significant,
neonatal, lumenal mucus accumulation. Our data suggest that TMEM16A
CaCC-mediated Cl- secretion appears to be necessary for normal airway
surface liquid homeostasis.},
url = {http://www.jbc.org/cgi/content/abstract/284/22/14875}
}
@ARTICLE{Rock2009a,
author = {Rock, Jason R. and Onaitis, Mark W. and Rawlins, Emma L. and Lu,
Yun and Clark, Cheryl P. and Xue, Yan and Randell, Scott H. and Hogan,
Brigid L. M.},
title = {Basal cells as stem cells of the mouse trachea and human airway epithelium},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {12771--12775},
number = {31},
month = aug,
abstract = {The pseudostratified epithelium of the mouse trachea and human airways
contains a population of basal cells expressing Trp-63 (p63) and
cytokeratins 5 (Krt5) and Krt14. Using a KRT5-CreERT2 transgenic
mouse line for lineage tracing, we show that basal cells generate
differentiated cells during postnatal growth and in the adult during
both steady state and epithelial repair. We have fractionated mouse
basal cells by FACS and identified 627 genes preferentially expressed
in a basal subpopulation vs. non-BCs. Analysis reveals potential
mechanisms regulating basal cells and allows comparison with other
epithelial stem cells. To study basal cell behaviors, we describe
a simple in vitro clonal sphere-forming assay in which mouse basal
cells self-renew and generate luminal cells, including differentiated
ciliated cells, in the absence of stroma. The transcriptional profile
identified 2 cell-surface markers, ITGA6 and NGFR, which can be used
in combination to purify human lung basal cells by FACS. Like those
from the mouse trachea, human airway basal cells both self-renew
and generate luminal daughters in the sphere-forming assay.},
url = {http://www.pnas.org/cgi/content/abstract/106/31/12771}
}
@ARTICLE{Rockel2009,
author = {Rockel, Jason and Bernier, Suzanne and Leask, Andrew},
title = {Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes
by TNFa-induced MEK/ERK signalling},
journal = {Arthritis Research \& Therapy},
year = {2009},
volume = {11},
pages = {R8},
number = {1},
abstract = {INTRODUCTION:TNFa is increased in the synovial fluid of patients with
rheumatoid arthritis and osteoarthritis. TNFa activates mitogen-activated
kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes;
however, the overall functional relevance of MEK/ERK to TNFa-regulated
gene expression in chondrocytes is unknown.METHODS:Chondrocytes were
treated with TNFa with or without the MEK1/2 inhibitor U0126 for
24 hours. Microarray analysis and real-time PCR analyses were used
to identify genes regulated by TNFa in a MEK1/2-dependent fashion.
Promoter/reporter, immunoblot, and electrophoretic mobility shift
assays were used to identify transcription factors whose activity
in response to TNFa was MEK1/2 dependent. Decoy oligodeoxynucleotides
bearing consensus transcription factor binding sites were introduced
into chondrocytes to determine the functionality of our results.RESULTS:Approximately
20% of the genes regulated by TNFa in chondrocytes were sensitive
to U0126. Transcript regulation of the cartilage-selective matrix
genes Col2a1, Agc1 and Hapln1, and of the matrix metalloproteinase
genes Mmp-12 and Mmp-9, were U0126 sensitive – whereas regulation
of the inflammatory gene macrophage Csf-1 was U0126 insensitive.
TNFa-induced regulation of Sox9 and NF?B activity was also U0126
insensitive. Conversely, TNFa-increased early growth response 1 (Egr-1)
DNA binding was U0126 sensitive. Transfection of chondrocytes with
cognate Egr-1 oligodeoxynucleotides attenuated the ability of TNFa
to suppress Col2a1, Agc1 or Hapln1 mRNA expression.CONCLUSIONS:Our
results suggest that MEK/ERK and Egr1 are required for TNFa-regulated
catabolic and anabolic genes of the cartilage extracellular matrix,
and hence may represent potential targets for drug intervention in
osteoarthritis or rheumatoid arthritis.},
doi = {10.1186/ar2595},
issn = {1478-6354},
pubmedid = {19144181},
url = {http://arthritis-research.com/content/11/1/R8}
}
@ARTICLE{Rockx2009,
author = {Rockx, Barry and Baas, Tracey and Zornetzer, Gregory A. and Haagmans,
Bart and Sheahan, Timothy and Frieman, Matthew and Dyer, Matthew
D. and Teal, Thomas H. and Proll, Sean and van den Brand, Judith
and Baric, Ralph and Katze, Michael G.},
title = {Early Upregulation of Acute Respiratory Distress Syndrome-Associated
Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe
Acute Respiratory Syndrome Coronavirus Infection},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {7062--7074},
number = {14},
month = jul,
abstract = {Several respiratory viruses, including influenza virus and severe
acute respiratory syndrome coronavirus (SARS-CoV), produce more severe
disease in the elderly, yet the molecular mechanisms governing age-related
susceptibility remain poorly studied. Advanced age was significantly
associated with increased SARS-related deaths, primarily due to the
onset of early- and late-stage acute respiratory distress syndrome
(ARDS) and pulmonary fibrosis. Infection of aged, but not young,
mice with recombinant viruses bearing spike glycoproteins derived
from early human or palm civet isolates resulted in death accompanied
by pathological changes associated with ARDS. In aged mice, a greater
number of differentially expressed genes were observed than in young
mice, whose responses were significantly delayed. Differences between
lethal and nonlethal virus phenotypes in aged mice could be attributed
to differences in host response kinetics rather than virus kinetics.
SARS-CoV infection induced a range of interferon, cytokine, and pulmonary
wound-healing genes, as well as several genes associated with the
onset of ARDS. Mice that died also showed unique transcriptional
profiles of immune response, apoptosis, cell cycle control, and stress.
Cytokines associated with ARDS were significantly upregulated in
animals experiencing lung pathology and lethal disease, while the
same animals experienced downregulation of the ACE2 receptor. These
data suggest that the magnitude and kinetics of a disproportionately
strong host innate immune response contributed to severe respiratory
stress and lethality. Although the molecular mechanisms governing
ARDS pathophysiology remain unknown in aged animals, these studies
reveal a strategy for dissecting the genetic pathways by which SARS-CoV
infection induces changes in the host response, leading to death.},
url = {http://jvi.asm.org/cgi/content/abstract/83/14/7062}
}
@ARTICLE{Rodd2008,
author = {Rodd, Zachary A. and Kimpel, Mark W. and Edenberg, Howard J. and
Bell, Richard L. and Strother, Wendy N. and McClintick, Jeanette
N. and Carr, Lucinda G. and Liang, Tiebing and McBride, William J.},
title = {Differential gene expression in the nucleus accumbens with ethanol
self-administration in inbred alcohol-preferring rats},
journal = {Pharmacology Biochemistry and Behavior},
year = {2008},
volume = {89},
pages = {481--498},
number = {4},
month = jun,
abstract = {The current study examined the effects of operant ethanol (EtOH) self-administration
on gene expression kin the nucleus accumbens (ACB) and amygdala (AMYG)
of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard
two-lever operant paradigm to administer either water-water, EtOH
(15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were
killed 24 h after the last operant session, and the ACB and AMYG
dissected; RNA was extracted and purified for microarray analysis.
For the ACB, there were 513 significant differences at the p < 0.01
level in named genes: 55 between SAC and water; 215 between EtOH
and water, and 243 between EtOH and SAC. In the case of the AMYG
(p < 0.01), there were 48 between SAC and water, 23 between EtOH
and water, and 63 between EtOH and SAC group. Gene Ontology (GO)
analysis indicated that differences in the ACB between the EtOH and
SAC groups could be grouped into 15 significant (p < 0.05) categories,
which included major categories such as synaptic transmission, cell
and ion homeostasis, and neurogenesis, whereas differences between
the EtOH and water groups had only 4 categories, which also included
homeostasis and synaptic transmission. Several genes were in common
between the EtOH and both the SAC and water groups in the synaptic
transmission (e.g., Cav2, Nrxn3, Gabrb2, Gad1, Homer1) and homeostasis
(S100b, Prkca, Ftl1) categories. Overall, the results suggest that
changes in gene expression in the ACB of iP rats are associated with
the reinforcing effects of EtOH.},
issn = {0091-3057},
keywords = {Microarrays, Gene expression, Ethanol self-administration, Alcohol-preferring
rats, Nucleus accumbens, Amygdala},
url = {http://www.sciencedirect.com/science/article/B6T0N-4RXJYK2-1/2/e4ef48fdf4d01b98e731f9252906a59c}
}
@ARTICLE{Rode2009,
author = {Rode, Tone Mari and Berget, Ingunn and Langsrud, Solveig and Møretrø,
Trond and Holck, Askild},
title = {MALDI-TOF mass spectrometry for quantitative gene expression analysis
of acid responses in Staphylococcus aureus},
journal = {Journal of Microbiological Methods},
year = {2009},
volume = {78},
pages = {86--93},
number = {1},
month = jul,
abstract = {Microorganisms are constantly exposed to new and altered growth conditions,
and respond by changing gene expression patterns. Several methods
for studying gene expression exist. During the last decade, the analysis
of microarrays has been one of the most common approaches applied
for large scale gene expression studies. A relatively new method
for gene expression analysis is MassARRAY, which combines real competitive-PCR
and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight)
mass spectrometry. In contrast to microarray methods, MassARRAY technology
is suitable for analysing a larger number of samples, though for
a smaller set of genes. In this study we compare the results from
MassARRAY with microarrays on gene expression responses of Staphylococcus
aureus exposed to acid stress at pH 4.5. RNA isolated from the same
stress experiments was analysed using both the MassARRAY and the
microarray methods. The MassARRAY and microarray methods showed good
correlation. Both MassARRAY and microarray estimated somewhat lower
fold changes compared with quantitative real-time PCR (qRT-PCR).
The results confirmed the up-regulation of the urease genes in acidic
environments, and also indicated the importance of metal ion regulation.
This study shows that the MassARRAY technology is suitable for gene
expression analysis in prokaryotes, and has advantages when a set
of genes is being analysed for an organism exposed to many different
environmental conditions.},
issn = {0167-7012},
keywords = {Acid stress, MALDI-TOF MS, MassARRAY, Microarray, Staphylococcus aureus},
url = {http://www.sciencedirect.com/science/article/B6T30-4W8TW0G-4/2/a7b43f0dba2799f9a2f35749a0a713ef}
}
@ARTICLE{Rodgers2006,
author = {Rodgers, Kathleen E. and Ellefson, Dolph D. and Espinoza, Theresa
and Hsu, Ya-hsuan and DiZerega, Gere S. and Mehrian-Shai, Ruty},
title = {Expression of intracellular filament, collagen, and collagenase genes
in diabetic and normal skin after injury},
journal = {Wound Repair and Regeneration},
year = {2006},
volume = {14},
pages = {298--305},
number = {3},
abstract = {ABSTRACT Reports have shown differences in gene expression in the
skin of diabetic and normal mice both at baseline and after injury.
Cluster analysis identified distinct expression patterns within intermediate
filaments and extracellular proteins. This report addresses the effect
of diabetes and injury on the expression of keratin-associated proteins,
keratin complexes, procollagen, and collagenase (matrix metalloproteinase;
MMP) genes. At baseline keratin-associated proteins and keratin complexes
gene expression was increased in diabetic mice. After surgery, the
level of expression for keratin-associated proteins and keratin complexes
genes decreased in diabetic mice, but did not change in normal mice.
If the expression of a procollagen gene differed between diabetic
and normal mice, the expression was lower in diabetic mice. Procollagen
gene expression was elevated after skin excision compared with noninjured
skin. At baseline, the level of MMP and tissue inhibitor of metalloproteinase
gene expression was comparable between mouse strains. With injury,
the expression of several MMP genes was increased in both mouse strains,
but to higher levels in diabetic mice. At day 7, the level of MMP-9
activity in granulation tissue was elevated. This alteration may
contribute to delayed healing in diabetic mice. Therefore, differences
in gene expression exist between mouse strains and can assist in
understanding of physiological manifestations, including delayed
healing, in diabetic mice.},
issn = {1524-475X},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1743-6109.2006.00124.x}
}
@ARTICLE{Rodius2007,
author = {Rodius, Sophie and Indra, Gitali and Thibault, Christelle and Pfister,
Véronique and Georges-Labouesse, Elisabeth},
title = {Loss of α6 integrins in keratinocytes leads to an increase in TGFβ
and AP1 signaling and in expression of differentiation genes},
journal = {J. Cell. Physiol.},
year = {2007},
volume = {212},
pages = {439--449},
number = {2},
abstract = {Abstract 10.1002/jcp.21040.abs Mice lacking the α6 integrin chain
die at birth with severe skin blistering. To further study the function
of α6 integrin in skin, we generated conditionally immortalized
cell lines from the epidermis of wild-type and α6 deficient mouse
embryos. Mutant cells presented a decreased adhesion on laminin 5,
the major component of the basement membrane in the skin, and on
laminins 10/11 and 2. A DNA array analysis revealed alterations in
the expression of extracellular matrix (ECM) components including
laminin 5, cytoskeletal elements, but also membrane receptors like
the hemidesmosomal components integrin β4 and collagen XVII, or
growth factors and signaling molecules of the TGFβ, EGF, and Wnt
pathways. Finally, an increase of several epidermal differentiation
markers was observed in cells and tissue at the protein level. Further
examination of the mutant tissue revealed alterations in the filaggrin
signal. These differences may be linked to an upregulation of the
TGFβ and the Jun/Fos pathways in mutant keratinocytes. These results
are in favor of a role for integrin α6β4 in the maintenance of
basal keratinocyte properties and epidermal homeostasis. J. Cell.
Physiol. 212: 439–449, 2007. © 2007 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.21040}
}
@ARTICLE{Rodrigues2007,
author = {Rodrigues, Ana-Joao and Coppola, Giovanni and Santos, Claudia and
Costa, Maria do Carmo and Ailion, Michael and Sequeiros, Jorge and
Geschwind, Daniel H. and Maciel, Patricia},
title = {Functional genomics and biochemical characterization of the C. elegans
orthologue of the Machado-Joseph disease protein ataxin-3},
journal = {FASEB J},
year = {2007},
volume = {21},
pages = {1126--1136},
number = {4},
month = apr,
abstract = {Machado-Joseph disease (MJD) is the most common dominant spinocerebellar
ataxia. MJD is caused by a CAG trinucleotide expansion in the ATXN3
gene, which encodes a protein named ataxin-3. Ataxin-3 has been proposed
to act as a deubiquitinating enzyme in the ubiquitin-proteasome pathway
and to be involved in transcriptional repression; nevertheless, its
precise biological function(s) remains unknown. To gain further insight
into the function of ataxin-3, we have identified the Caenorhabditis
elegans orthologue of the ATXN3 gene and characterized its pattern
of expression, developmental regulation, and subcellular localization.
We demonstrate that, analogous to its human orthologue, C. elegans
ataxin-3 has deubiquitinating activity in vitro against polyubiquitin
chains with four or more ubiquitins, the minimum ubiquitin length
for proteasomal targeting. To further evaluate C. elegans ataxin-3,
we characterized the first known knockout animal models both phenotypically
and biochemically, and found that the two C. elegans strains were
viable and displayed no gross phenotype. To identify a molecular
phenotype, we performed a large-scale microarray analysis of gene
expression in both knockout strains. The data revealed a significant
deregulation of core sets of genes involved in the ubiquitin-proteasome
pathway, structure/motility, and signal transduction. This gene identification
provides important clues that can help elucidate the specific biological
role of ataxin-3 and unveil some of the physiological effects caused
by its absence or diminished function.--Rodrigues, A-J., Coppola,
G., Santos, C., do Carmo Costa, M., Ailion, M., Sequeiros, J., Geschwind,
D. H., Maciel, P. Functional genomics and biochemical characterization
of the C. elegans orthologue of the Machado-Joseph disease protein
ataxin-3.},
url = {http://www.fasebj.org/cgi/content/abstract/21/4/1126}
}
@ARTICLE{Rodrigues2009,
author = {Rodrigues, C.F.D. and Urbano, A.M. and Matoso, E. and Carreira, I.
and Almeida, A. and Santos, P. and Botelho, F. and Carvalho, L. and
Alves, M. and Monteiro, C. and Costa, A.N. and Moreno, V. and Alpoim,
M.C.},
title = {Human bronchial epithelial cells malignantly transformed by hexavalent
chromium exhibit an aneuploid phenotype but no microsatellite instability},
journal = {Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis},
year = {2009},
volume = {670},
pages = {42--52},
number = {1-2},
month = nov,
abstract = {Hexavalent chromium [Cr(VI)] is a well-recognized human lung carcinogen.
In order to gain further insight into Cr(VI)-induced carcinogenesis,
we have established an adequate in vitro cellular model for the study
of this process. To this end, BEAS-2B cells were used. Chronic exposure
of cells to 1 [mu]M Cr(VI) induced changes in the cells' ploidy and
a decrease in cloning efficiency, although cultures continued to
progress to confluence. After prolonged exposure (12 passages), the
culture became heterogeneous, exhibiting areas where apparently normal
epithelial cells and morphologically altered cells coexisted. Subsequent
culture at a very low density strongly accentuated the Cr(VI)-induced
changes in morphology and pattern of growth. Three individual colonies
were then ring-cloned and expanded into three subclonal aneuploid
cell lines. These subclonal cell lines showed changes in growth pattern
and morphology, as well as a karyotype drift concomitant with the
overexpression of genes commonly involved in malignant transformation
(c-MYC, EGFR, HIF-1[alpha] and LDH-A). Moreover, when one of these
cell lines (RenG2) was injected into nude mice, it showed the ability
to induce tumors. This cell line revealed no microsatellite instability
(MSI), which points to the expression of a functional MLH1 protein
and an active mismatch repair (MMR) system. Therefore, the progression
to malignancy of the BEAS-2B cells involved Cr(VI)-induced transformants
that retained the ability to repair DNA damage, suggesting that genotoxicity
underlies the ongoing carcinogenic process.},
issn = {0027-5107},
keywords = {Hexavalent chromium, Lung cancer, BEAS-2B cells, Malignant transformation,
Microsatellite instability, Mismatch repair system},
url = {http://www.sciencedirect.com/science/article/B6T2C-4WSHK9V-2/2/1a46c1274a2683bae04c85f6513c613b}
}
@ARTICLE{Rodrigues2011,
author = {Rodrigues, Gerard A. and Maurier-Mahe, Florence and Shurland, Dixie-Lee
and Mclaughlin, Anne and Luhrs, Keith and Throo, Emeline and Delalonde-Delaunay,
Laurence and Pallares, Diego and Schweighoffer, Fabien and Donello,
John},
title = {Differential Effects of PPAR{gamma} Ligands on Oxidative Stress-Induced
Death of Retinal Pigmented Epithelial Cells},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {890--903},
number = {2},
month = feb,
abstract = {Purpose.To investigate the role of the peroxisome proliferator-activated
receptor (PPAR)-{gamma} in modulating retinal pigmented epithelium
(RPE) responses to oxidative stress. Methods.ARPE-19 cells were treated
with the oxidant, t-butylhydroperoxide (tBH) to induce apoptosis.
Cells pretreated with synthetic PPAR{gamma} agonists of the antidiabetic
thiazolidinediones class before tBH challenge were assessed for viability
and, by microarray analysis, for effects on gene expression. Results.Treatment
of ARPE-19 cells with tBH resulted in a loss of viability and global
changes in the pattern of gene expression. PPAR{gamma} ligands were
found to have differential modulatory effects on tBH-induced apoptosis
of RPE cells. Whereas rosiglitazone and pioglitazone potentiated
cell death, troglitazone acted as a potent cytoprotective agent.
Downregulation of PPAR{gamma} expression by an siRNA resulted in
enhanced cell death in response to tBH treatment and blocked the
cytoprotective effect of troglitazone consistent with a role of PPAR{gamma}
in mediating this response. Microarray analysis revealed that while
rosiglitazone and pioglitazone had little effect on gene changes
induced by tBH treatment, troglitazone dramatically reduced the number
of changes caused by oxidative stress. A unique subset of genes that
were deregulated by tBH and selectively normalized by troglitazone
were identified. Conclusions.These findings demonstrate that PPAR{gamma}
agonists can have differential effects on RPE survival in response
to oxidative stress. Oxidative stress leads to deregulation of a
large set of genes in ARPE-19 cells. A specific subset of these genes
can be selectively modulated by troglitazone and represent potential
novel targets for cytoprotective therapies.},
comment = {10.1167/iovs.10-5715},
url = {http://www.iovs.org/cgi/content/abstract/52/2/890}
}
@ARTICLE{Rodriguez2006,
author = {Rodriguez, K. F. and Blomberg, L. A. and Zuelke, K. A. and Miles,
J. R. and Alexander, J. E. and Farin, C. E.},
title = {Identification of candidate mRNAs associated with gonadotropin-induced
maturation of murine cumulus oocyte complexes using serial analysis
of gene expression},
journal = {Physiol Genomics},
year = {2006},
volume = {27},
pages = {318--327},
number = {3},
month = nov,
abstract = {In cultured cumulus oocyte complexes (COC), FSH induces gene transcription
required for germinal vesicle breakdown (GVBD). Experiments were
performed to determine the critical period when gene transcription
is required for GVBD and to identify candidate mRNAs involved. Experiment
I: murine COC were cultured 4 h in the presence of FSH with 5,6-dichloro-1-{beta}-D-ribofuranosylbenzimidazole
(DRB) added at different intervals after the start of culture. COC
cultured with FSH underwent GVBD (82 {+/-} 7%). When DRB was added
at 0, 5, or 10 min after culture initiation, oocyte maturation was
blocked (17 {+/-} 7, 14 {+/-} 6, and 21 {+/-} 6% GVBD, respectively).
When DRB was added after 15, 20, or 30 min, progressively more COC
underwent GVBD (37 {+/-} 6, 39 {+/-} 6, and 66 {+/-} 6%, respectively).
The critical period of transcription required for GVBD occurred between
15 and 30 min after culture initiation. Experiment II: COC were cultured
for 25 min in the presence (plusDRB) or absence (minusDRB) of DRB.
SAGE libraries were generated from COC RNA of each treatment group.
A total of 48,431 and 45,367 tags were sequenced for the plusDRB
and minusDRB libraries, respectively. Criteria used to identify transcripts
of interest included a total tag count of at least 10 across both
libraries and a threefold or greater difference in expression between
libraries. Using these criteria, 39 and 27 transcripts were identified
as differentially expressed at the P [≤] 0.01 and P [≤] 0.001
levels, respectively. Differentially expressed transcripts were classed
into major categories that included cell growth, development, and
regulation of gene expression. Differentially expressed transcripts
represent candidates potentially involved in regulating maturation
of murine COC.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/27/3/318}
}
@ARTICLE{Rodriguez2010,
author = {Rodriguez, Maria C. Suarez and Edsgärd, Daniel and Hussain, Syed
S. and Alquezar, David and Rasmussen, Morten and Gilbert, Thomas
and Nielsen, Bjørn H. and Bartels, Dorothea and Mundy, John},
title = {Transcriptomes of the desiccation-tolerant resurrection plant Craterostigma
plantagineum},
journal = {The Plant Journal},
year = {2010},
volume = {63},
pages = {212--228},
number = {2},
abstract = {Summary Studies of the resurrection plant Craterostigma plantagineum
have revealed some of the mechanisms which these desiccation-tolerant
plants use to survive environments with extreme dehydration and restricted
seasonal water. Most resurrection plants are polyploid with large
genomes, which has hindered efforts to obtain whole genome sequences
and perform mutational analysis. However, the application of deep
sequencing technologies to transcriptomics now permits large-scale
analyses of gene expression patterns despite the lack of a reference
genome. Here we use pyro-sequencing to characterize the transcriptomes
of C. plantagineum leaves at four stages of dehydration and rehydration.
This reveals that genes involved in several pathways, such as those
required for vitamin K and thiamin biosynthesis, are tightly regulated
at the level of gene expression. Our analysis also provides a comprehensive
picture of the array of cellular responses controlled by gene expression
that allow resurrection plants to survive desiccation.},
issn = {1365-313X},
keywords = {desiccation tolerance, expressed sequence tags, pyro-sequencing, resurrection
plant},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04243.x}
}
@ARTICLE{Rodriguez2011,
author = {Rodriguez, Rene and Rubio, Ruth and Gutierrez-Aranda, Ivan and Melen,
Gustavo J. and Elosua, Carolina and GarcÃa-Castro, Javier and Menendez,
Pablo},
title = {FUS-CHOP Fusion Protein Expression Coupled to p53 Deficiency Induces
Liposarcoma in Mouse but Not in Human Adipose-Derived Mesenchymal
Stem/Stromal Cells},
journal = {STEM CELLS},
year = {2011},
volume = {29},
pages = {179--192},
number = {2},
abstract = {Abstract Human sarcomas have been modeled in mice by expression of
specific fusion genes in mesenchymal stem cells (MSCs). However,
sarcoma models based on human MSCs are still missing. We attempted
to develop a model of liposarcoma by expressing FUS (FUsed in Sarcoma;
also termed TLS, Translocated in LipoSarcoma)-CHOP (C/EBP HOmologous
Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3), a
hallmark mixoid liposarcoma-associated fusion oncogene, in wild-type
and p53-deficient mouse and human adipose-derived mesenchymal stem/stromal
cells (ASCs). FUS-CHOP induced liposarcoma-like tumors when expressed
in p53−/− but not in wild-type (wt) mouse ASCs (mASCs). In the
absence of FUS-CHOP, p53−/− mASCs forms leiomyosarcoma, indicating
that the expression of FUS-CHOP redirects the tumor genesis/phenotype.
FUS-CHOP expression in wt mASCs does not initiate sarcomagenesis,
indicating that p53 deficiency is required to induce FUS-CHOP-mediated
liposarcoma in fat-derived mASCs. In a human setting, p53-deficient
human ASCs (hASCs) displayed a higher in vitro growth rate and a
more extended lifespan than wt hASCs. However, FUS-CHOP expression
did not induce further changes in culture homeostasis nor initiated
liposarcoma in either wt or p53-depleted hASCs. These results indicate
that FUS-CHOP expression in a p53-deficient background is sufficient
to initiate liposarcoma in mouse but not in hASCs, suggesting the
need of additional cooperating mutations in hASCs. A microarray gene
expression profiling has shed light into the potential deregulated
pathways in liposarcoma formation from p53-deficient mASCs expressing
FUS-CHOP, which might also function as potential cooperating mutations
in the transformation process from hASCs. STEM CELLS 2011; 29:179–192},
doi = {10.1002/stem.571},
issn = {1549-4918},
keywords = {Mesenchymal stem cells, Adipose-derived mesenchymal stem/stromal cells,
Liposarcoma, Fusion genes, FUS-CHOP, p53, Sarcomagenesis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/stem.571}
}
@ARTICLE{Rodriguez2007,
author = {Rodriguez, Virginia and Chen, Yidong and Elkahloun, Abdel and Dutra,
Amalia and Pak, Evgenia and Chandrasekharappa, Settara},
title = {Chromosome 8 BAC array comparative genomic hybridization and expression
analysis identify amplification and overexpression of TRMT12 in breast
cancer},
journal = {Genes Chromosom. Cancer},
year = {2007},
volume = {46},
pages = {694--707},
number = {7},
abstract = {Abstract 10.1002/gcc.20454.abs Genomic changes in chromosome 8 are
commonly observed in breast cancer cell lines and tumors. To fine
map such genomic changes by comparative genomic hybridization (CGH),
a high resolution (100 kb) chromosome 8 array that can detect single
copy changes was developed using Phi29 DNA polymerase amplified BAC
(bacterial artificial chromosome) DNA. The BAC array CGH resolved
the two known amplified regions (8q21 and 8q24) of a breast cancer
cell line (SKBR3) into nine separate regions including six amplicons
and three deleted regions, all of which were verified by Fluorescence
in situ hybridization. The extent of the gain/loss for each region
was validated by qPCR. CGH was performed with a total of 8 breast
cancer cell lines, and common regions of genomic amplification/deletion
were identified by segmentation analysis. A 1.2-Mb region (125.3–126.5
Mb) and a 1.0-Mb region (128.1–129.1 Mb) in 8q24 were amplified
in 7/8 cell lines. A global expression analysis was performed to
evaluate expression changes associated with genomic amplification/deletion:
a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines,
showed highest expression in these cell lines. Further analysis by
RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed
>2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a
yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional
modification of tRNAPhe, and exploring the biological consequence
of its altered expression, may reveal novel pathways in tumorigenesis.
This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
Published 2007 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20454}
}
@ARTICLE{Rodriguez-Castillo2010,
author = {Rodriguez-Castillo, Araceli and Vaughan, Gilberto and Ramirez-Gonzalez,
Jose Ernesto and Escobar-Gutierrez, Alejandro},
title = {Simultaneous Cocirculation of Both European Varicella-Zoster Virus
Genotypes (E1 and E2) in Mexico City},
journal = {J. Clin. Microbiol.},
year = {2010},
volume = {48},
pages = {1712--1715},
number = {5},
month = may,
abstract = {Full-length genome analysis of varicella-zoster virus (VZV) has shown
that viral strains can be classified into seven different genotypes:
European (E), Mosaic (M), and Japanese (J), and the E and M genotypes
can be further subclassified into E1, E2, and M1 through 4, respectively.
The distribution of the main VZV genotypes in Mexico was described
earlier, demonstrating the predominance of E genotype, although other
genotypes (M1 and M4) were also identified. However, no information
regarding the circulation of either E genotype in the country is
available. In the present study, we confirm the presence of both
E1 and E2 genotypes in the country and explore the possibility of
coinfection as the triggering factor for increased virulence among
severe cases. A total of 61 different European VZV isolates collected
in the Mexico City metropolitan area from 2005 to 2006 were typed
by using a PCR method based on genotype-specific primer amplification.
Fifty isolates belonged to the E1 genotype, and the eleven remaining
samples were classified as E2 genotypes. No coinfection with both
E genotypes was identified among these specimens. We provide here
new information on the distribution of VZV genotypes circulating
in Mexico City.},
url = {http://jcm.asm.org/cgi/content/abstract/48/5/1712}
}
@ARTICLE{Rodriguez-Cuenca2010,
author = {Rodriguez-Cuenca, Sergio and Cochemé, Helena M. and Logan, Angela
and Abakumova, Irina and Prime, Tracy A. and Rose, Claudia and Vidal-Puig,
Antonio and Smith, Anthony C. and Rubinsztein, David C. and Fearnley,
Ian M. and Jones, Bruce A. and Pope, Simon and Heales, Simon J.R.
and Lam, Brian Y.H. and Neogi, Sudeshna Guha and McFarlane, Ian and
James, Andrew M. and Smith, Robin A.J. and Murphy, Michael P.},
title = {Consequences of long-term oral administration of the mitochondria-targeted
antioxidant MitoQ to wild-type mice},
journal = {Free Radical Biology and Medicine},
year = {2010},
volume = {48},
pages = {161--172},
number = {1},
month = jan,
abstract = {The mitochondria-targeted quinone MitoQ protects mitochondria in animal
studies of pathologies in vivo and is being developed as a therapy
for humans. However, it is unclear whether the protective action
of MitoQ is entirely due to its antioxidant properties, because long-term
MitoQ administration may alter whole-body metabolism and gene expression.
To address this point, we administered high levels of MitoQ orally
to wild-type C57BL/6 mice for up to 28 weeks and investigated the
effects on whole-body physiology, metabolism, and gene expression,
finding no measurable deleterious effects. In addition, because antioxidants
can act as pro-oxidants under certain conditions in vitro, we examined
the effects of MitoQ administration on markers of oxidative damage.
There were no changes in the expression of mitochondrial or antioxidant
genes as assessed by DNA microarray analysis. There were also no
increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin,
and the activities of mitochondrial enzymes were unchanged. Therefore,
MitoQ does not act as a pro-oxidant in vivo. These findings indicate
that mitochondria-targeted antioxidants can be safely administered
long-term to wild-type mice.},
issn = {0891-5849},
keywords = {Mitochondria, Antioxidants, MitoQ, Mouse, In vivo, Metabolism, Free
radicals},
url = {http://www.sciencedirect.com/science/article/B6T38-4XHM16S-2/2/611871ddd60a7d976e09e489e6867988}
}
@ARTICLE{RODRIGUEZ-LANETTY2009,
author = {RODRIGUEZ-LANETTY, MAURICIO and HARII, SAKI and HOEGH-GULDBERG, OVE},
title = {Early molecular responses of coral larvae to hyperthermal stress},
journal = {Molecular Ecology},
year = {2009},
volume = {18},
pages = {5101--5114},
number = {24},
abstract = {Abstract Most of the work on the impact of elevated temperature and
light on Symbiodinium-invertebrate symbioses have focused primarily
on how the photosynthetic (algal) partner is impacted. Understanding
how the same stresses affect the invertebrate host, however, is in
its infancy. In this study, we re-examined the direct effect of elevated
temperatures on the invertebrate host exploring the early transcriptional
response of aposymbiotic (without algal symbionts) coral larvae.
The temperatures tested in the experimental design were 24 °C (ambient
seawater temperature), 28 °C and 31 °C; and the sampling points
were 3 and 10Â h after temperature exposure. We explored relative
changes in transcription using a cDNA microarray constructed for
the scleractinian coral, Acropora millepora, and containing 18Â 142
expressed sequence tag (EST) clones/8386 unigenes. Our study identified
29 genes that were significantly up- and down-regulated when A. millepora
coral larvae were exposed to elevated temperatures. Down-regulation
of several key components of DNA/RNA metabolism was detected implying
inhibition of general cellular processes. The down-regulation of
protein synthesis, however, was not simple and random, which suggested
that the stress response was a more complicated adjustment of cellular
metabolism. We identified four significant outcomes during the very
early hours of the transcriptional response to hyperthermal stress
in coral larvae. First, the expression of heat-shock proteins increased
rapidly (within 3Â h) in response to hyperthermal stress. Second,
a fluorescent protein homologue, DsRed-type FP, decreased its expression
in response to elevated temperature reinforcing a potential role
as a molecular marker for monitoring hyperthermal stress in nature.
Third, the down-regulation of a coral mannose-binding C-type lectin
under elevated temperature suggests that heat stress might compromise
some components of the coral immune defence and therefore might bring
about susceptibility to pathogenic diseases. And last, genes involved
in protecting cells against oxidative stress showed little response
at the early hours to heat stress, supporting the proposal that up-regulation
of cnidarian host oxidative stress genes may require reactive oxygen
species generated by stressed algal symbionts.},
issn = {1365-294X},
keywords = {climate change, coral larvae, coral stress response, ecological genomics,
microarray},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2009.04419.x}
}
@ARTICLE{Rodriguez-Osorio2007,
author = {Rodriguez-Osorio, N. and Kim, I. J. and Wang, H. and Kaya, A. and
Memili, E.},
title = {Melatonin increases cleavage rate of porcine preimplantation embryos
in vitro},
journal = {Journal of Pineal Research},
year = {2007},
volume = {43},
pages = {283--288},
number = {3},
abstract = {Abstract:  Melatonin has been used to promote in vitro embryo development
in different species. This study determined the effects of melatonin
on in vitro porcine embryo development; in particular, cleavage rate,
blastocyst rate, and blastocyst cell number. Starting 5Â hr after
insemination, porcine zygotes were cultured in porcine zygote medium
3 (PZM-3) culture medium supplemented with melatonin at increasing
concentrations (10−12 m, 10−9 m, 10−6 m, 10−3 m). Melatonin
at a concentration of 10−9 m had a positive effect on cleavage
rates, while the highest concentration of melatonin (10−3 m) significantly
decreased cleavage rates. Although blastocyst rates were not increased
by 10−9 m melatonin, blastocyst cell numbers were significantly
higher for embryos subjected to 10−9 m melatonin. The expression
levels of the pro-apoptotic gene BAX and anti-apoptotic gene BCL2L1
in blastocysts were not affected by the presence of melatonin in
the culture medium. To further study the protective properties of
10−9 m melatonin against stressful conditions, hydrogen peroxide
(0.01 mm) and heat (40°C) were used during embryo culture. The
addition of melatonin to embryos subjected to 40°C for 3 hr increased
cleavage rates, but had no protective effect for embryos subjected
to 0.01Â mm H2O2, probably because the physiological levels of melatonin
could not counteract the pharmacological levels of H2O2. Our data
indicate that 10−9 m melatonin has a positive effect on porcine
embryo cleavage rates and blastocyst total cell numbers and it might
have a protective effect against heat stress.},
issn = {1600-079X},
keywords = {Development, embryo, melatonin, porcine},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-079X.2007.00475.x}
}
@ARTICLE{Rodriguez-Osorio2010,
author = {Rodriguez-Osorio, Nelida and Wang, Hongfeng and Rupinski, Jennifer
and Bridges, Susan M. and Memili, Erdogan},
title = {Comparative functional genomics of mammalian DNA methyltransferases},
journal = {Reproductive BioMedicine Online},
year = {2010},
volume = {20},
pages = {243--255},
number = {2},
month = feb,
abstract = {DNA methylation involves biochemical modification of DNA by addition
of methyl groups onto CpG dinucleotides, and this epigenetic mechanism
regulates gene expression in disease and development. Mammalian DNA
methyltransferases, DNMT (DNMT1, DNMT3A and DNMT3B), together with
the accessory protein DNMT3L establish specific DNA methylation patterns
in the genome during gametogenesis, embryogenesis and somatic tissue
development. The present study addresses the structural and functional
conservation of the DNMT in humans, mice and cattle and the patterns
of mRNA abundance of the different enzymes during embryogenesis to
improve understanding of epigenetic regulation in early development.
The findings showed a high degree of structural and functional conservation
among the human, mouse, and bovine DNMT. The results also showed
similar patterns of transcript abundance for all of the proteins
at different stages of early embryo development. Remarkably, all
of the DNMT with an important role in DNA methylation (DNMT1, DNMT3A,
DNMT3B, and DNMT3L) show a greater degree of structural similarity
between human and bovine than that between human and mouse. These
results have important implications for the selection of an appropriate
model for study of DNA methylation during early development in humans.},
issn = {1472-6483},
keywords = {Bovine, embryogenesis, DNA methylation, epigenetics},
url = {http://www.sciencedirect.com/science/article/B986R-4XX1617-1/2/ef1563d7fc526214920e23a27b5427f1}
}
@ARTICLE{Rodriguez-Osorio2009,
author = {Rodriguez-Osorio, Nelida and Wang, Zhongde and Kasinathan, Poothappillai
and Page, Grier and Robl, James and Memili, Erdogan},
title = {Transcriptional reprogramming of gene expression in bovine somatic
cell chromatin transfer embryos},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {190},
number = {1},
abstract = {BACKGROUND:Successful reprogramming of a somatic genome to produce
a healthy clone by somatic cells nuclear transfer (SCNT) is a rare
event and the mechanisms involved in this process are poorly defined.
When serial or successive rounds of cloning are performed, blastocyst
and full term development rates decline even further with the increasing
rounds of cloning. Identifying the "cumulative errors" could reveal
the epigenetic reprogramming blocks in animal cloning.RESULTS:Bovine
clones from up to four generations of successive cloning were produced
by chromatin transfer (CT). Using Affymetrix bovine microarrays we
determined that the transcriptomes of blastocysts derived from the
first and the fourth rounds of cloning (CT1 and CT4 respectively)
have undergone an extensive reprogramming and were more similar to
blastocysts derived from in vitro fertilization (IVF) than to the
donor cells used for the first and the fourth rounds of chromatin
transfer (DC1 and DC4 respectively). However a set of transcripts
in the cloned embryos showed a misregulated pattern when compared
to IVF embryos. Among the genes consistently upregulated in both
CT groups compared to the IVF embryos were genes involved in regulation
of cytoskeleton and cell shape. Among the genes consistently upregulated
in IVF embryos compared to both CT groups were genes involved in
chromatin remodelling and stress coping.CONCLUSION:The present study
provides a data set that could contribute in our understanding of
epigenetic errors in somatic cell chromatin transfer. Identifying
"cumulative errors" after serial cloning could reveal some of the
epigenetic reprogramming blocks shedding light on the reprogramming
process, important for both basic and applied research.},
doi = {10.1186/1471-2164-10-190},
issn = {1471-2164},
pubmedid = {19393066},
url = {http://www.biomedcentral.com/1471-2164/10/190}
}
@ARTICLE{Rodriguez-Pla2009,
author = {Rodriguez-Pla, Alicia and Martinez-Murillo, Francisco and Savino,
Peter J. and Eagle, Ralph C., Jr and Seo, Philip and Soloski, Mark
J.},
title = {MMP-12, a novel matrix metalloproteinase associated with giant cell
arteritis},
journal = {Rheumatology},
year = {2009},
volume = {48},
pages = {1460--1461},
number = {11},
month = nov,
url = {http://rheumatology.oxfordjournals.org}
}
@ARTICLE{RodrAguez-Alvarez2010,
author = {RodrÃguez-Alvarez, Lleretny and Sharbati, Jutta and Sharbati, Soroush
and Cox, José Francisco and Einspanier, Ralf and Castro, Fidel Ovidio},
title = {Differential gene expression in bovine elongated (Day 17) embryos
produced by somatic cell nucleus transfer and in vitro fertilization},
journal = {Theriogenology},
year = {2010},
volume = {74},
pages = {45--59},
number = {1},
month = jul,
abstract = {Somatic cloning in cattle is associated with impaired embryo development,
caused by inappropriate epigenetic reprogramming during embryogenesis;
however, there is a paucity of data regarding gene expression at
the critical elongation and peri-implantation stages. The objective
of the present study was to identify genes differentially expressed
in bovine cloned embryos at Day 17 of development (Day 0=day of nucleus
transfer or IVF). Day 7 blastocysts (Hand Made Cloned or IVP) were
transferred to recipient cattle and collected at Day 17. The efficiency
of recovery of elongated embryos was similar, however cloned embryos
elongated less than IVP embryos (91.8±45.8 vs. 174±50mm) and fewer
had embryonic discs (63 vs. 83%). Qualitative and quantitative PCR
detected expression of OCT4, NANOG, IFNtau, EOMES, FGF4, SOX2, and
CDX2 in all IVP embryos. In most cloned embryos, NANOG and FGF4 were
absent (verified by qPCR); NANOG, EOMES, and FGF4 were underexpressed,
whereas IFNtau was overexpressed in cloned embryos. Based on qPCRs,
other genes, i.e., SPARC, SNRB1, and CBPP22, were down-regulated
in cloned embryos, whereas HSP70 and TDKP1 were overexpressed. In
bovine microarrays, 47 genes (3.6%) were deregulated in cloned embryos,
including several involved in trophoblast growth and differentiation.
In conclusion, we inferred that these data were indicative of incomplete
epigenetic reprogramming after cloning; this could lead to aberrant
gene expression and subsequently early pregnancy loss. There was
an apparent association between incomplete morphological elongation
and aberrant reprogramming of a subset of genes critical for early
embryonic development.},
issn = {0093-691X},
keywords = {Hand-Made Cloning, Microarray, Trophoblast, Elongation},
publisher = {Elsevier},
refid = {S0093-691X(10)00055-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0093691X10000555?showall=true}
}
@ARTICLE{RodrAguez-Penas2011,
author = {Diego RodrÃguez-Penas and Sandra Feijóo-BandÃn and Pamela V. Lear
and Ana Mosquera-Leal and Vanessa GarcÃa-Rúa and Manuel F. Otero
and Miguel Rivera and Oreste Gualillo and José Ramón González-Juanatey
and Francisca Lago},
title = {Aliskiren affects fatty-acid uptake and lipid-related genes in rodent
and human cardiomyocytes},
journal = {Biochemical Pharmacology},
year = {2011},
volume = {82},
pages = {491 - 504},
number = {5},
abstract = {Purpose We investigated whether the direct renin inhibitor aliskiren
can affect metabolism in cardiomyocytes from rat, mouse and human
sources. Methods and results At 10–50 μmol/L, aliskiren significantly
increased medium-chain-fatty-acid uptake in primary-cultured neonatal-rat
and HL-1 adult-mouse-derived cardiomyocytes (BODIPY-induced fluorescence
intensity). The fatty-acid transporter CD-36 was correspondingly
translocated to, but the glucose transporter Glut-4 away from, the
sarcoplasmic reticulum/plasma membrane, in primary-cultured neonatal-rat
(CD-36, Glut-4) and adult-human (CD-36) cardiomyocytes (confocal
immunocytochemistry). Immunoblotting showed that aliskiren induced
phosphorylation of ERK1/2 in cardiomyocytes from all three sources;
responses were dose- and time-dependent, unaffected by renin treatment,
and did not cause alterations in expression of (P)R or Igf2/M6P receptors.
Microarray analysis of the complete genome of aliskiren-treated neonatal-rat
cardiomyocytes, with RT-qPCR and immunoblot confirmation assays in
rat and human primary cardiomyocytes, showed that aliskiren up-regulated
mRNA and increased protein expression of several enzymes important
in lipid and glucose metabolism and in cholesterol biosynthesis.
Cardiomyocyte cell-cycle and viability were unaffected by aliskiren.
Conclusions Aliskiren can induce changes in fatty-acid and glucose
uptake and expression of key enzymes of lipid and cholesterol metabolism,
which are not associated with increased expression of (P)R or Igf2/M6P
receptors, in cultured cardiomyocytes.},
doi = {10.1016/j.bcp.2011.05.021},
issn = {0006-2952},
keywords = {Cardiomyocytes},
url = {http://www.sciencedirect.com/science/article/pii/S0006295211003340}
}
@ARTICLE{Rodriguez2011a,
author = {Armando Alexei Rodríguez and Juliana Silva Cassoli and Fei Sa and
Zhi Qiang Dong and José Carlos de Freitas and Adriano M.C. Pimenta
and Maria Elena de Lima and Katsuhiro Konno and Simon Ming Yuen Lee
and Anoland Garateix and André J. Zaharenko},
title = {Peptide fingerprinting of the neurotoxic fractions isolated from
the secretions of sea anemones Stichodactyla helianthus and Bunodosoma
granulifera. New members of the APETx-like family identified by a
454 pyrosequencing approach},
journal = {Peptides},
year = {2011},
volume = {na},
pages = { - },
number = {0},
abstract = {Sea anemones are known to contain a wide diversity of biologically
active peptides, mostly unexplored according to recent peptidomic
and transcriptomic studies. In the present work, the neurotoxic fractions
from the exudates of Stichodactyla helianthus and Bunodosoma granulifera
were analyzed by reversed-phase chromatography and mass spectrometry.
The first peptide fingerprints of these sea anemones were assessed,
revealing the largest number of peptide components (156) so far found
in sea anemone species, as well as the richer peptide diversity of
B. granulifera in relation to S. helianthus. The transcriptomic analysis
of B. granulifera, performed by massive cDNA sequencing with 454
pyrosequencing approach allowed the discovery of five new APETx-like
peptides (U-AITX-Bg1a–e – including the full sequences of their
precursors for four of them), which together with type 1 sea anemone
sodium channel toxins constitute a very distinguishable feature of
studied sea anemone species belonging to genus Bunodosoma. The molecular
modeling of these new APETx-like peptides showed a distribution of
positively charged and aromatic residues in putative contact surfaces
as observed in other animal toxins. On the other hand, they also
showed variable electrostatic potentials, thus suggesting a docking
onto their targeted channels in different spatial orientations. Moreover
several crab paralyzing toxins (other than U-AITX-Bg1a–e), which
induce a variety of symptoms in crabs, were isolated. Some of them
presumably belong to new classes of crab-paralyzing peptide toxins,
especially those with molecular masses below 2 kDa, which represent
the smallest peptide toxins found in sea anemones.},
doi = {10.1016/j.peptides.2011.10.011},
issn = {0196-9781},
keywords = {Sea anemone},
url = {http://www.sciencedirect.com/science/article/pii/S0196978111004189}
}
@ARTICLE{Rodriguez-Quinones2008,
author = {Rodríguez-Quiñones, José and Irizarry, Rafael and Díaz-Blanco, Nitza
and Rivera-Molina, Félix and Gómez-Garzón, Diana and Rodríguez-Medina,
José},
title = {Global mRNA expression analysis in myosin II deficient strains of
Saccharomyces cerevisiae reveals an impairment of cell integrity
functions},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {34},
number = {1},
abstract = {BACKGROUND:The Saccharomyces cerevisiae MYO1 gene encodes the myosin
II heavy chain (Myo1p), a protein required for normal cytokinesis
in budding yeast. Myo1p deficiency in yeast (myo1?) causes a cell
separation defect characterized by the formation of attached cells,
yet it also causes abnormal budding patterns, formation of enlarged
and elongated cells, increased osmotic sensitivity, delocalized chitin
deposition, increased chitin synthesis, and hypersensitivity to the
chitin synthase III inhibitor Nikkomycin Z. To determine how differential
expression of genes is related to these diverse cell wall phenotypes,
we analyzed the global mRNA expression profile of myo1? strains.RESULTS:Global
mRNA expression profiles of myo1? strains and their corresponding
wild type controls were obtained by hybridization to yeast oligonucleotide
microarrays. Results for selected genes were confirmed by real time
RT-PCR. A total of 547 differentially expressed genes (p = 0.01)
were identified with 263 up regulated and 284 down regulated genes
in the myo1? strains. Gene set enrichment analysis revealed the significant
over-representation of genes in the protein biosynthesis and stress
response categories. The SLT2/MPK1 gene was up regulated in the microarray,
and a myo1?slt2? double mutant was non-viable. Overexpression of
ribosomal protein genes RPL30 and RPS31 suppressed the hypersensitivity
to Nikkomycin Z and increased the levels of phosphorylated Slt2p
in myo1? strains. Increased levels of phosphorylated Slt2p were also
observed in wild type strains under these conditions.CONCLUSION:Following
this analysis of global mRNA expression in yeast myo1? strains, we
conclude that 547 genes were differentially regulated in myo1? strains
and that the stress response and protein biosynthesis gene categories
were coordinately regulated in this mutant. The SLT2/MPK1 gene was
confirmed to be essential for myo1? strain viability, supporting
that the up regulated stress response genes are regulated by the
PKC1 cell integrity pathway. Suppression of Nikkomycin Z hypersensitivity
together with Slt2p phosphorylation was caused by the overexpression
of ribosomal protein genes RPL30 and RPS31. These ribosomal protein
mRNAs were down regulated in the myo1? arrays, suggesting that down
regulation of ribosomal biogenesis may affect cell integrity in myo1?
strains.},
doi = {10.1186/1471-2164-9-34},
issn = {1471-2164},
owner = {Meike Kuschel},
pubmedid = {18215314},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2164/9/34}
}
@ARTICLE{Rodriguez-Ramirez2011,
author = {Rodríguez-Ramírez, Roberto and González-Córdova, Aarón F. and Vallejo-Cordoba,
Belinda},
title = {Review: Authentication and traceability of foods from animal origin
by polymerase chain reaction-based capillary electrophoresis},
journal = {Analytica Chimica Acta},
year = {2011},
volume = {685},
pages = {120--126},
number = {2},
month = jan,
abstract = {This work presents an overview of the applicability of PCR-based capillary
electrophoresis (CE) in food authentication and traceability of foods
from animal origin. Analytical approaches for authenticating and
tracing meat and meat products and fish and seafood products are
discussed. Particular emphasis will be given to the usefulness of
genotyping in food tracing by using CE-based genetic analyzers.},
issn = {0003-2670},
keywords = {Food authentication and traceability, Food DNA, Capillary electrophoresis},
url = {http://www.sciencedirect.com/science/article/pii/S0003267010014364}
}
@ARTICLE{Rody2007,
author = {Rody, A. and Karn, T. and Solbach, C. and Gaetje, R. and Munnes,
M. and Kissler, S. and Ruckhäberle, E. and Minckwitz, G.v. and Loibl,
S. and Holtrich, U. and Kaufmann, M.},
title = {The erbB2+ cluster of the intrinsic gene set predicts tumor response
of breast cancer patients receiving neoadjuvant chemotherapy with
docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO
trial},
journal = {The Breast},
year = {2007},
volume = {16},
pages = {235--240},
number = {3},
month = jun,
abstract = {Summary Gene expression profiling using Affymetrix HG-U133 Arrays
(22,500 genes) was performed on fresh frozen pretherapeutic core
biopsies from 50 patients undergoing neoadjuvant chemotherapy (NAC)
with docetaxel, adriamycin, cyclophosphamide (TAC) within the GEPARTRIO
trial. The Sorlie classification based on the "intrinsic gene set"
revealed four different subgroups in our cohort (normal-like: 14%,
basal-like: 20%, erbB2+: 22% and luminal: 44%), which is in line
with the original description. High genomic grade but not histopathological
grading was statistically different within the four subgroups (P<0.001).
About 45.5% of tumors classified according to erbB2+ cluster showed
a pathological complete response compared to 0% in the normal-like,
10.0% in the basal-like and 9.1% in the luminal subgroup (P=0.024).
There was a trend to less tumor relapses in the erbB2+ subgroup (0%)
compared to the normal-like (28.6%), basal-like (30.0%) and luminal
(13.6%) cluster (P=0.215). Our data suggest that the molecular tumor
subtypes based on the "intrinsic gene set" can be used to predict
tumor response according to NAC.},
issn = {0960-9776},
keywords = {Intrinsic gene set, Molecular classification, ErbB2, Neoadjuvant chemotherapy,
Breast cancer},
url = {http://www.sciencedirect.com/science/article/B6WC2-4NJ26HG-1/2/09ccb3536cac14627c537e359a768739}
}
@ARTICLE{Roepke2008,
author = {Roepke, T. A. and Xue, C. and Bosch, M. A. and Scanlan, T. S. and
Kelly, M. J. and Ronnekleiv, O. K.},
title = {Genes Associated with Membrane-Initiated Signaling of Estrogen and
Energy Homeostasis},
journal = {Endocrinology},
year = {2008},
volume = {149},
pages = {6113--6124},
number = {12},
month = dec,
abstract = {During the reproductive cycle, fluctuations in circulating estrogens
affect multiple homeostatic systems controlled by hypothalamic neurons.
Two of these neuronal populations are arcuate proopiomelanocortin
and neuropeptide Y neurons, which control energy homeostasis and
feeding. Estradiol modulates these neurons either through the classical
estrogen receptors (ERs) to control gene transcription or through
a G protein-coupled receptor (mER) activating multiple signaling
pathways. To differentiate between these two divergent ER-mediated
mechanisms and their effects on homeostasis, female guinea pigs were
ovariectomized and treated systemically with vehicle, estradiol benzoate
(EB) or STX, a selective mER agonist, for 4 wk, starting 7 d after
ovariectomy. Individual body weights were measured after each injection
day for 28 d, at which time the animals were euthanized, and the
arcuate nucleus was microdissected. As predicted, the body weight
gain was significantly lower for EB-treated females after d 5 and
for STX-treated females after d 12 compared with vehicle-treated
females. Total arcuate RNA was extracted from all groups, but only
the vehicle and STX-treated samples were prepared for gene microarray
analysis using a custom guinea pig gene microarray. In the arcuate
nucleus, 241 identified genes were significantly regulated by STX,
several of which were confirmed by quantitative real-time PCR and
compared with EB-treated groups. The lower weight gain of EB-treated
and STX-treated females suggests that estradiol controls energy homeostasis
through both ER{alpha} and mER-mediated mechanisms. Genes regulated
by STX indicate that not only does it control neuronal excitability
but also alters gene transcription via signal transduction cascades
initiated from mER activation.},
url = {http://endo.endojournals.org/cgi/content/abstract/149/12/6113}
}
@ARTICLE{RoeschEly2005,
author = {Roesch Ely, Mariana and Nees, Matthias and Karsai, Syrus and Mägele,
Ira and Bogumil, Ralf and Vorderwülbecke, Sonja and Ruess, Alexandra
and Dietz, Andreas and Schnölzer, Martina and Bosch, Franz X.},
title = {Transcript and proteome analysis reveals reduced expression of calgranulins
in head and neck squamous cell carcinoma},
journal = {European Journal of Cell Biology},
year = {2005},
volume = {84},
pages = {431--444},
number = {2-3},
month = mar,
issn = {0171-9335},
keywords = {Proteomics, SELDI-TOF MS, HNSCC, S100 and annexin protein family,
Protein biomarkers},
url = {http://www.sciencedirect.com/science/article/B7GJ2-4FG4V6N-2/2/c77055ce40e7a38b0bf83d3549ead9b1}
}
@ARTICLE{Roesch2008,
author = {Roesch, Alexander and Mueller, Andrea M. and Stempfl, Thomas and
Moehle, Christoph and Landthaler, Michael and Vogt, Thomas},
title = {RBP2-H1/JARID1B is a transcriptional regulator with a tumor suppressive
potential in melanoma cells},
journal = {Int. J. Cancer},
year = {2008},
volume = {122},
pages = {1047--1057},
number = {5},
abstract = {Abstract 10.1002/ijc.23211.abs The RBP2-H1/JARID1B nuclear protein
belongs to the ARID family of DNA-binding proteins and is a potential
tumor suppressor that is lost during melanoma development. As we
have recently shown, one physiological function of RBP2-H1/JARID1B
is to exert cell cycle control via maintenance of active retinoblastoma
protein. We now add new evidence that RBP2-H1/JARID1B can also directly
regulate gene transcription in a reporter assay system, either alone
or as part of a multimolecular complex together with the developmental
transcription factors FOXG1b and PAX9. In melanoma cells, chromatin
immunoprecipitation combined with promoter chip analysis (ChIP-on-chip)
suggests a direct binding of re-expressed RBP2-H1/JARID1B to a multitude
of human regulatory chromosomal elements (promoters, enhancers and
introns). Among those, a set of 23 genes, including the melanoma
relevant genes CDK6 and JAG-1 could be confirmed by cDNA microarray
analyses to be differentially expressed after RBP2-H1/JARID1B re-expression.
In contrast, in nonmelanoma HEK 293 cells, RBP2-H1/JARID1B overexpression
only evokes a minor transcriptional response in cDNA microarray analyses.
Because the transcriptional regulation in melanoma cells is accompanied
by an inhibition of proliferation, an increase in caspase activity
and a partial cell cycle arrest in G1/0, our data support an anti-tumorigenic
role of RBP2-H1/JARID1B in melanocytic cells. © 2007 Wiley-Liss,
Inc.},
issn = {1097-0215},
keywords = {melanoma, transcription, gene expression, retinoblastoma protein binding
protein, apoptosis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23211}
}
@ARTICLE{Roessler2010,
author = {Roessler, Stephanie and Jia, Hu-Liang and Budhu, Anuradha and Forgues,
Marshonna and Ye, Qing-Hai and Lee, Ju-Seog and Thorgeirsson, Snorri
S. and Sun, Zhongtang and Tang, Zhao-You and Qin, Lun-Xiu and Wang,
Xin Wei},
title = {A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse
in Early-Stage Hepatocellular Carcinoma Patients},
journal = {Cancer Res.},
year = {2010},
volume = {70},
pages = {10202--10212},
number = {24},
month = dec,
abstract = {Metastasis-related recurrence often occurs in hepatocellular carcinoma
(HCC) patients who receive curative therapies. At present, it is
challenging to identify patients with high risk of recurrence, which
would warrant additional therapies. In this study, we sought to analyze
a recently developed metastasis-related gene signature for its utility
in predicting HCC survival, using 2 independent cohorts consisting
of a total of 386 patients who received radical resection. Cohort
1 contained 247 predominantly HBV-positive cases analyzed with an
Affymetrix platform, whereas cohort 2 contained 139 cases with mixed
etiology analyzed with the NCI Oligo Set microarray platform. We
employed a survival risk prediction algorithm with training, test,
and independent cross-validation strategies and found that the gene
signature is predictive of overall and disease-free survival. Importantly,
risk was significantly predicted independently of clinical characteristics
and microarray platform. In addition, survival prediction was successful
in patients with early disease, such as small (<5 cm in diameter)
and solitary tumors, and the signature predicted particularly well
for early recurrence risk (<2 years), especially when combined with
serum alpha fetoprotein or tumor staging. In conclusion, we have
shown in 2 independent cohorts with mixed etiologies and ethnicity
that the metastasis gene signature is a useful tool to predict HCC
outcome, suggesting the general utility of this classifier. We recommend
the use of this classifier as a molecular diagnostic test to assess
the risk that an HCC patient will develop tumor relapse within 2
years after surgical resection, particularly for those with early-stage
tumors and solitary presentation. Cancer Res; 70(24); 10202-12. (C)2010
AACR.},
comment = {10.1158/0008-5472.CAN-10-2607},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/70/24/10202}
}
@ARTICLE{Rofatto2009,
author = {Rofatto, Henrique K. and Tararam, Cibele A. and Borges, William C.
and Wilson, R. Alan and Leite, Luciana C.C. and Farias, Leonardo
P.},
title = {Characterization of phosphodiesterase-5 as a surface protein in the
tegument of Schistosoma mansoni},
journal = {Molecular and Biochemical Parasitology},
year = {2009},
volume = {166},
pages = {32--41},
number = {1},
month = jul,
abstract = {Schistosoma mansoni is a major causative agent of schistosomiasis,
an important parasitic disease that constitutes a severe health problem
in developing countries. Even though an effective treatment exists,
it does not prevent re-infection and the development of an effective
vaccine still remains the most desirable means of control for this
disease. In this work we describe the cloning and characterization
of a S. mansoni nucleotide pyrophosphatase/phosphosdiesterase type
5 (SmNPP-5), previously identified in the tegument by proteomic studies.
In silico analysis predicts an N-terminal signal peptide, three N-glycosylation
sites and a C-terminal transmembrane domain similar to that described
for mammalian isoforms. Real-time quantitative RT-PCR and Western
blot analyses determined that SmNPP-5 is significantly upregulated
in the transition from free-living cercaria to schistosomulum and
adult worm parasitic stages; additionally, the native protein was
demonstrated to be N-glycosylated. Immunolocalization experiments
and tegument surface membrane preparations confirm the protein as
a tegument surface protein. Furthermore, the ectolocalization of
this enzyme was corroborated through the hydrolysis of the phosphodiesterase
specific substrate ([rho]-Nph-5'-TMP) by living adult and 21-day-old
worms. Interestingly, pre-incubation of adult and 21-day-old worms
with anti-rSmNPP-5 antibody was able to reduce by 50-60% the enzyme
activity. These results suggest that SmNPP-5 is closely associated
with the new tegument surface generation after cercarial penetration,
and being located at the host-parasite interface, is a potential
target for immune intervention.},
issn = {0166-6851},
keywords = {Schistosoma mansoni, Nucleotide pyrophosphatase/phosphodiesterase
(NPP) activity, Surface exposed, Tegument, N-glycosylated},
url = {http://www.sciencedirect.com/science/article/B6T29-4VP6650-3/2/ee17326ccd4bbb0b095913cfaa0291ca}
}
@ARTICLE{Roff2008,
author = {Roff, Alanna and Wilson, Robin Taylor},
title = {A novel SNP in a vitamin D response element of the CYP24A1 promoter
reduces protein binding, transactivation, and gene expression},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2008},
volume = {112},
pages = {47--54},
number = {1-3},
month = nov,
abstract = {The active form of vitamin D (1[alpha],25(OH)2D3) is known to have
antiproliferative effects and has been implicated in cancers of the
colon, breast, and prostate. These cancers occur more frequently
among African Americans than Caucasians, and individuals with African
ancestry are known to have approximately twofold lower levels of
serum vitamin D (25(OH)D) compared with individuals of European ancestry.
However, epidemiological studies of the vitamin D receptor (VDR)
have shown inconsistent associations with cancer risk, suggesting
that differences in other genes in the pathway may be important.
We sought to identify functionally significant polymorphic variants
in CYP24A1, a gene that is highly inducible by 1[alpha],25(OH)2D3
and that encodes the primary catabolic enzyme in the pathway. Here
we report the identification of six novel SNPs in the human CYP24A1
promoter, including one at nucleotide -279 occurring within the distal
vitamin D response element (VDRE2). Our experiments demonstrate that
the VDRE2 variant results in decreased protein binding and transactivation
in vitro, and reduced expression of CYP24A1 in cultured primary human
lymphocytes provides evidence for an effect in vivo. This variant
was only observed in our African American population, and represents
a first step toward understanding differences in disease risk among
racial/ethnic groups.},
issn = {0960-0760},
keywords = {CYP24A1, 24-Hydroxylase, Promoter, 1[alpha],25(OH)2D3, Vitamin D receptor,
Single nucleotide polymorphism, VDRE},
url = {http://www.sciencedirect.com/science/article/B6T8X-4TCR1N1-1/2/48c6dbcd5d79dfadb5c4b0dd0d11034b}
}
@ARTICLE{Rogasch2006,
author = {Rogasch, Kathrin and Ruhmling, Vanessa and Pane-Farre, Jan and Hoper,
Dirk and Weinberg, Christin and Fuchs, Stephan and Schmudde, Mareike
and Broker, Barbara M. and Wolz, Christiane and Hecker, Michael and
Engelmann, Susanne},
title = {Influence of the Two-Component System SaeRS on Global Gene Expression
in Two Different Staphylococcus aureus Strains},
journal = {J. Bacteriol.},
year = {2006},
volume = {188},
pages = {7742--7758},
number = {22},
month = nov,
abstract = {The two-component system SaeRS consisting of the histidin kinase SaeS
and the response regulator SaeR is known to act on virulence gene
expression in Staphylococcus aureus. In order to get a more comprehensive
picture on SaeR-regulated genes, we studied the contribution of the
two-component system on global gene expression by using both the
proteomic and transcriptomic approach. Altogether, a loss of SaeRS
resulted in a decreased amount of at least 17 extracellular proteins
and two cell surface-associated proteins, among them several important
virulence factors such as HlgA, HlgB, HlgC, LukF, and LukM. SaeRS
activates the expression of these genes at the transcriptional level.
The amount of the five proteins Aur, SspA, SsaA, Plc, and GlpQ was
negatively influenced by SaeRS. However, the transcription of the
corresponding genes was not affected by the two-component system.
SaeRS had also no measurable influence on the transcription of the
regulatory genes agr, sarA, arlRS, and sigB that contribute to the
regulation of SaeRS-dependent virulence factors identified in this
investigation. Our results clearly show that SaeRS is strongly involved
in the tight temporal control of virulence factor expression in S.
aureus. Its precise role within the regulatory network remains to
be determined.},
url = {http://jb.asm.org/cgi/content/abstract/188/22/7742}
}
@ARTICLE{Rogers2007,
author = {Rogers, James V. and Choi, Young W. and Giannunzio, Lenore F. and
Sabourin, Patrick J. and Bornman, Daniel M. and Blosser, Emily G.
and Sabourin, Carol L.K.},
title = {Transcriptional responses in spleens from mice exposed to Yersinia
pestis CO92},
journal = {Microbial Pathogenesis},
year = {2007},
volume = {43},
pages = {67--77},
number = {2-3},
month = aug,
abstract = {Yersinia pestis is one of the most threatening biological agents due
to the associated high mortality and history of plague pandemics.
Identifying molecular players in the host response to infection may
enable the development of medical countermeasures against Y. pestis.
In this study, microarrays were used to identify the host splenic
response mechanisms to Y. pestis infection. Groups of Balb/c mice
were injected intraperitoneally with 2-257 CFU of Y. pestis strain
CO92 or vehicle. One group was assessed for mortality rates and another
group for transcriptional analysis. The time to death at the 8 and
257 CFU challenge doses were 5.0±2.3 and 3.8±0.4 days, respectively.
Gene profiling using Affymetrix Mouse Genome 430 2.0 Arrays revealed
no probe sets were significantly altered for all five mice in the
low-dose group when compared to the vehicle controls. However, 534
probe sets were significantly altered in the high dose versus vehicle
controls; 384 probe sets were down-regulated and 150 probe sets were
up-regulated. The predominant biological processes identified were
immune function, cytoskeletal, apoptosis, cell cycle, and protein
degradation. This study provides new information on the underlying
transcriptional mechanisms in mice to Y. pestis infection.},
issn = {0882-4010},
keywords = {Yersinia pestis, Plague, Microarray, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6WN6-4NJ209K-2/2/8c228d54858301f4eb81e360b2b2bebf}
}
@ARTICLE{Rogers2009,
author = {Rogers, Nicola Jane and Lees, Mark Jeffrey and Gabriel, Luisa and
Maniati, Eleni and Rose, Sarah Jane and Potter, Paul Keith and Morley,
Bernard John},
title = {A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus
Development via Failure to Clear Apoptotic Cells},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {1982--1990},
number = {4},
month = feb,
abstract = {Systemic lupus erythematosus is a multisystem autoimmune disease characterized
by the production of numerous antinuclear autoantibodies and inflammatory
mediators. The BXSB mouse strain is an excellent model of the disease.
Previous work has determined a number of important disease susceptibility
intervals that have been isolated in separate congenic strains. Here,
we have combined expression data from those strains with functional
analyses to demonstrate that reduced expression of the innate scavenger
receptor Marco (macrophage receptor with collagenous structure) is
a primary event in BXSB mice, that reduced mRNA expression is mirrored
at the protein level, and that this results in a significant alteration
in function. We have confirmed a role for Marco in the clearance
of apoptotic cells and a generalized defect in both endocytosis and
phagocytosis. The failure to clear apoptotic cells has previously
been linked to the development of systemic lupus erythematosus. However,
the use of congenic mice with limited phenotypes in this study has
enabled us to propose that in the case of Marco at least, disease
results from the production of anti-dsDNA Abs.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/4/1982}
}
@ARTICLE{Rogerson2008,
author = {Rogerson, Lynsey and Darby, Steve and Jabbar, Talal and Mathers,
Marie E. and Leung, Hing Y. and Robson, Craig N. and Sahadevan, Kanagasabai
and O’Toole, Kieran and Gnanapragasam, Vincent J.},
title = {Application of transcript profiling in formalin-fixed paraffin-embedded
diagnostic prostate cancer needle biopsies},
journal = {BJU International},
year = {2008},
volume = {102},
pages = {364--370},
number = {3},
abstract = {OBJECTIVE To investigate the feasibility of transcript profiling in
diagnostic formalin-fixed and paraffin-embedded (FFPE) biopsies for
prostate cancer. MATERIALS AND METHODS Laser-capture microdissection
(LCM) was used to microdissect glandular epithelium as well as stromal
tissue in archival prostate needle biopsies. Optimized RNA extraction,
reverse transcription and real-time PCR (QPCR) protocols were used
to detect transcript expression. RNA degradation effects were assessed
using hydrolysed cell line RNA and matched xenograft FFPE and frozen
tumours. RESULTS LCM and RNA extraction was achieved in all biopsies
from a pilot cohort of five patients. cDNA produced was successfully
used to detect expression of glyceraldehyde-3-phosphate dehydrogenase,
RPL13, prostate-specific antigen, vimentin, inhibitor of differentiation/DNA
binding 1 (Id-1) and polycomb group protein enhancer of zeste homolog
2 (EZH2) transcripts. In the cell line and xenograft models, we investigated
the effect of RNA degradation on transcript quantification by QPCR.
In both models normalization of transcript quantity with a housekeeping
gene resulted in restored expression in all degraded samples to within
a 50% difference of control samples. Using an extended cohort of
29 biopsies, we tested application in detecting differences in EZH2
and Id-1 expression between malignant and benign epithelium. The
results confirmed that our technique was capable of quantifying significant
differences in expression between malignant and benign epithelium
consistent with the reported trends. CONCLUSION This study reports
the use of standard FFPE needle biopsies for transcript profiling
and supports the concept of molecular prognostic studies in tissue
acquired at diagnosis in prostate cancer.},
issn = {1464-410X},
keywords = {prostate cancer, needle biopsy, FFPE, transcript profile, laser capture},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-410X.2008.07627.x}
}
@ARTICLE{Roghanian2010,
author = {Roghanian, Ali and Jones, Des C. and Pattisapu, Jogi V. and Wolfe,
Jonathan and Young, Neil T. and Behnam, Babak},
title = {Filament-associated TSGA10 protein is expressed in professional antigen
presenting cells and interacts with vimentin},
journal = {Cellular Immunology},
year = {2010},
volume = {265},
pages = {120--126},
number = {2},
abstract = {Testis-specific gene antigen 10 (TSGA10) encodes an 82-kDa protein
expressed during development, and in testis and brain tissues. We
report its expression in human monocyte-derived dendritic cells (DC)
and macrophages in vitro and in murine spleen CD11c+ cells ex vivo.
An interaction between DC/macrophage-derived TSGA10 and vimentin,
as well as a few other major cytoskeletal proteins (e.g., actin-[gamma]1),
was identified by pull-down and mass spectroscopy assays. The interaction
between TSGA10 and vimentin was further confirmed by immunoprecipitation
and immunolocalisation in transfected RAW267 and HEK293 cell lines.
TSGA10 formed filamentous structures in transfected COS-1 cells and
was observed in cellular projections. We propose that TSGA10 could
influence the function of antigen presenting cells (APC) via its
interaction with cytoskeletal proteins such as vimentin.},
issn = {0008-8749},
keywords = {TSGA10, Vimentin, Dendritic cell, Macrophage, Intermediate filament},
url = {http://www.sciencedirect.com/science/article/B6WCF-50NYWVY-2/2/8588ff663b3cbf34c3d052a189e901fb}
}
@ARTICLE{Rogler2004,
author = {Rogler, Charles E. and Tchaikovskaya, Tatyana and Norel, Raquel and
Massimi, Aldo and Plescia, Christopher and Rubashevsky, Eugeny and
Siebert, Paul and Rogler, Leslie E.},
title = {RNA expression microarrays (REMs), a high-throughput method to measure
differences in gene expression in diverse biological samples},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {e120--},
number = {15},
month = aug,
abstract = {We have developed RNA expression microarrays (REMs), in which each
spot on a glass support is composed of a population of cDNAs synthesized
from a cell or tissue sample. We used simultaneous hybridization
with test and reference (housekeeping) genes to calculate an expression
ratio based on normalization with the endogenous reference gene.
A test REM containing artificial mixtures of liver cDNA and dilutions
of the bacterial LysA gene cDNA demonstrated the feasibility of detecting
transcripts at a sensitivity of four copies of LysA mRNA per liver
cell equivalent. Furthermore, LysA cDNA detection varied linearly
across a standard curve that matched the sensitivity of quantitative
real-time PCR. In REMs with real samples, we detected organ-specific
expression of albumin, Hnf-4 and Igfbp-1, in a set of mouse organ
cDNA populations and c-Myc expression in tumor samples in paired
tumor/normal tissue cDNA samples. REMs extend the use of classic
microarrays in that a single REM can contain cDNAs from hundreds
to thousands of cell or tissue samples each representing a specific
physiological or pathophysiological state. REMs will extend the analysis
of valuable samples by providing a common broad based platform for
their analysis and will promote research aimed at defining gene functions,
by broadening our understanding of their expression patterns in health
and disease.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/15/e120}
}
@ARTICLE{Rogue2012,
author = {Rogue, Alexandra and Lambert, Carine and Spire, Catherine and Claude,
Nancy and Guillouzo, Andre},
title = {Interindividual Variability in Gene Expression Profiles in Human
Hepatocytes and Comparison with HepaRG Cells},
journal = {Drug Metab. Dispos.},
year = {2012},
volume = {40},
pages = {151-158},
number = {1},
abstract = {Interindividual variations in functions other than drug metabolism
activity, remain poorly elucidated in human liver. In the present
study, the whole transcriptome of several human hepatocyte populations
and the differentiated human HepaRG cell line have been analyzed
and compared, using oligonucleotide pangenomic microarrays. We show
that, although the variation in the percentages of expressed genes
did not exceed 14% among the primary human hepatocyte populations,
huge interindividual differences in the transcript levels of many
genes were observed. These genes were related to various functions;
in addition to drug metabolism, they mainly concerned carbohydrate,
amino acid, and lipid metabolism. HepaRG cells expressed from 81
to 92% of the genes active in human hepatocytes and, in addition,
a specific gene subset mainly related to their transformed status,
some chromosomal abnormalities, and the presence of primitive biliary
epithelial cells. Of interest, a relationship was evidenced between
abnormal basal expression levels of some target genes and their corresponding
previously reported fold changes in one of four human hepatocyte
populations treated with the hepatotoxic drug troglitazone and not
with other nonhepatotoxic peroxisome proliferator-activated receptor
agonists (PLoS One 6:e18816, 2011). Taken together, our results support
the view that HepaRG cells express most of the genes active in primary
human hepatocytes and show that expression of most human hepatic
genes can quantitatively greatly vary among individuals, thereby
contributing to explain the huge interindividual variability in susceptibility
to drugs and other environmental factors.},
doi = {10.1124/dmd.111.042028},
eprint = {http://dmd.aspetjournals.org/cgi/reprint/40/1/151.pdf},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/40/1/151}
}
@ARTICLE{Rogue2011,
author = {Rogue, Alexandra and Renaud, Marie Pierre and Claude, Nancy and Guillouzo,
André and Spire, Catherine},
title = {Comparative gene expression profiles induced by PPAR[gamma] and PPAR[alpha]/[gamma]
agonists in rat hepatocytes},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {254},
pages = {18-31},
abstract = {Species-differential toxic effects have been described with PPAR[alpha]
and PPAR[gamma] agonists between rodent and human liver. PPAR[alpha]
agonists (fibrates) are potent hypocholesterolemic agents in humans
while they induce peroxisome proliferation and tumors in rodent liver.
By contrast, PPAR[gamma] agonists (glitazones) and even dual PPAR[alpha]/[gamma]
agonists (glitazars) have caused idiosyncratic hepatic and nonhepatic
toxicities in human without evidence of any damage in rodent during
preclinical studies. The mechanisms involved in such differences
remain largely unknown. Several studies have identified the major
target genes of PPAR[alpha] agonists in rodent liver while no comprehensive
analysis has been performed on gene expression changes induced by
PPAR[gamma] and dual PPAR[alpha]/[gamma] agonists. Here, we investigated
transcriptomes of rat hepatocytes after 24 h treatment with two PPAR[gamma]
(troglitazone and rosiglitazone) and two PPAR[alpha]/[gamma] (muraglitazar
and tesaglitazar) agonists. Although, hierarchical clustering revealed
a gene expression profile characteristic of each PPAR agonist class,
only a limited number of genes was specifically deregulated by glitazars.
Functional analyses showed that many genes known as PPAR[alpha] targets
were also modulated by both PPAR[gamma] and PPAR[alpha]/[gamma] agonists
and quantitative differences in gene expression profiles were observed
between these two classes. Moreover, most major genes modulated in
rat hepatocytes were also found to be deregulated in rat liver after
tesaglitazar treatment. Taken altogether, these results support the
conclusion that differential toxic effects of PPAR[alpha] and PPAR[gamma]
agonists in rodent liver do not result from transcriptional deregulation
of major PPAR target genes but rather from qualitative and/or quantitative
differential responses of a small subset of genes.},
issn = {0041-008X},
keywords = {Cryopreserved rat hepatocytes, PPAR[gamma], PPAR[alpha], Gene profiling,
Glitazones, Glitazars},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11001347}
}
@ARTICLE{Rogulski2005,
author = {Rogulski, Kenneth R. and Cohen, Debra E. and Corcoran, David L. and
Benos, Panayiotis V. and Prochownik, Edward V.},
title = {Deregulation of common genes by c-Myc and its direct target, MT-MC1},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {18968--18973},
number = {52},
month = dec,
abstract = {In addition to its role in cancer, the c-Myc oncoprotein controls
many normal cellular processes as a consequence of its function as
a basic helix-loop-helix leucine zipper transcription factor. Determining
which of the myriad genes under c-Myc control are relevant for these
various roles is thus a major challenge. mt-mc1 is a direct c-Myc
target gene whose overexpression recapitulates multiple c-Myc phenotypes,
including transformation. Using transcriptional profiling, we now
show that MT-MC1-overexpressing myeloid cells misregulate a total
of 47 distinct transcripts, a large proportion of which are involved
in signal transduction and/or cancer. Analysis of these genes reveals
a consensus promoter structure consisting of multiple, often closely
spaced c-Myc binding sites and three additional Wilm's tumor and
Egr1-like motifs. More than one-third of MT-MC1 target genes are
also clustered on six cancer-associated chromosomal loci. Most surprisingly,
all of the transcripts examined also are regulated by c-Myc. Finally,
an estrogen receptor-MT-MC1 fusion protein was used to establish
that all examined transcripts were regulated directly by the chimeric
protein. Our results thus indicate that MT-MC1 target genes largely
comprise a subset of those regulated by c-Myc. We propose that the
properties imparted by MT-MC1 are the result of its control of a
small and select c-Myc target gene population.},
url = {http://www.pnas.org/cgi/content/abstract/102/52/18968}
}
@ARTICLE{Rohan2011,
author = {Rohan, Stephen M and Xiao, Yonghong and Liang, Yupu and Dudas, Maria
E and Al-Ahmadie, Hikmat A and Fine, Samson W and Gopalan, Anuradha
and Reuter, Victor E and Rosenblum, Marc K and Russo, Paul and Tickoo,
Satish K},
title = {Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical
analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible
factor pathway-related proteins},
journal = {Mod Pathol},
year = {2011},
pages = {--},
month = may,
issn = {1530-0285},
publisher = {United States and Canadian Academy of Pathology, Inc.},
url = {http://dx.doi.org/10.1038/modpathol.2011.80}
}
@ARTICLE{Rohani2010,
author = {Rohani, Maryam G. and Beyer, Richard P. and Hacker, Beth M. and Dommisch,
Henrik and Dale, Beverly A. and Chung, Whasun O.},
title = {Modulation of expression of innate immunity markers CXCL5/ENA-78
and CCL20/MIP3{alpha} by protease-activated receptors (PARs) in human
gingival epithelial cells},
journal = {Innate Immunity},
year = {2010},
volume = {16},
pages = {104--114},
number = {2},
month = apr,
abstract = {Protease-activated receptors (PARs) are G-protein-coupled receptors
with an active role in host defense. The two most highly expressed
members of the PAR family in gingival epithelial cells (GECs) are
PAR1 and PAR2. The major virulence factors of periodontal pathogen
Porphyromonas gingivalis are its proteases which can activate PAR2.
However, little is known about the function of PARs in GECs when
they are activated by their endogenous agonist enzymes. The purpose
of this study was to characterize how the expression of innate immune
markers is modulated when PAR1 and PAR2 are activated by their agonist
enzymes, thrombin and trypsin, respectively. Here, we report that
activation of PAR1 and PAR2 induces cell proliferation at low concentration.
Activation of PAR via proteolytic activity of thrombin and trypsin
induces expression of CXCL5/ENA-78 and CCL20/MIP3{alpha} in a concentration-dependent
manner. Induction of CXCL5 via PAR1 was inhibited in the presence
of PAR1 cleavage blocking antibodies and by PAR1 siRNA. The induction
of CXCL5 and CCL20 via PAR2 was inhibited by PAR2 siRNA. These findings
indicate an active role in innate immune responses by PAR1 and PAR2
in GECs. Modulation of innate immunity by PARs may contribute to
co-ordinated and balanced immunosurveillance in GECs.},
url = {http://ini.sagepub.com/cgi/content/abstract/16/2/104}
}
@ARTICLE{Rohrbeck2010,
author = {Rohrbeck, Astrid and Salinas, Gabriela and Maaser, Kerstin and Linge,
Jens and Salovaara, Susan and Corvi, Raffaella and Borlak, Juergen},
title = {Toxicogenomics Applied to In Vitro Carcinogenicity Testing with Balb/c
3T3 Cells Revealed a Gene Signature Predictive of Chemical Carcinogens},
journal = {Toxicol. Sci.},
year = {2010},
volume = {118},
pages = {31--41},
number = {1},
month = nov,
abstract = {Information on the carcinogenic potential of chemicals is primarily
available for High Production Volume (HPV) products. Because of the
limited knowledge gain from routine cancer bioassays and the fact
that HPV chemicals are tested only, there is the need for more cost-effective
and informative testing strategies. Here we report the application
of advanced genomics to a cellular transformation assay to identify
toxicity pathways and gene signatures predictive for carcinogenicity.
Specifically, genome-wide gene expression analysis and quantitative
real time polymerase chain reaction (qRT-PCR) were applied to untransformed
and transformed mouse fibroblast Balb/c 3T3 cells that were exposed
to either 2, 4-diaminotoluene, benzo(a)pyrene, 2-acetylaminoflourene,
or 3-methycholanthrene at IC20 conditions for 24 and 120 h, respectively.
Then, bioinformatics was applied to define toxicity pathways and
a gene signature predictive of the carcinogenic risk of these chemicals.
Although bioinformatics revealed distinct differences for individual
chemicals at the gene-level pathway, analysis identified common perturbation
that resulted in an identification of 14 genes whose regulation in
cancer tissue had already been established. Strikingly, this gene
signature was identified in short-term (24 and 120 h) untransformed
and transformed cells (3 weeks), therefore demonstrating robustness
for its predictive power. The developed testing strategy thus identified
commonly regulated carcinogenic pathways and a gene signature that
predicted the risk for carcinogenicity for three well-known carcinogens.
Overall, the testing strategy warrants in-depth validation for the
prediction of carcinogenic risk of industrial chemicals in in vitro
carcinogenicity assay.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/118/1/31}
}
@ARTICLE{Roig2012,
author = {Roig, Barbara and Moyano, SÃlvia and Martorell, Lourdes and Costas,
Javier and Vilella, Elisabet},
title = {The Discoidin domain receptor 1 gene has a functional A2RE sequence},
journal = {Journal of Neurochemistry},
year = {2012},
volume = {120},
pages = {408--418},
number = {3},
abstract = {J. Neurochem. (2012) 120, 408–418.AbstractDiscoidin domain receptor
1 (DDR1) is expressed in myelin oligodendrocytes and co-localizes
with myelin basic protein (MBP). Alternative splicing of DDR1 generates
five isoforms designated DDR1a–e. The MBP mRNA contains an hnRNP
A2 response element (A2RE) sequence that is recognized by heterogeneous
nuclear ribonucleoprotein (hnRNP) A2/B1, which is responsible for
transport of the MBP mRNA to oligodendrocyte processes. We hypothesized
that DDR1 could have a functional A2RE sequence. By in silico analysis,
we identified an A2RE-like sequence in the human DDR1 mRNA. We observed
nuclear and dendrite cytoplasmic immunofluorescence, indicating that
DDR1 and hnRNP A2/B1 co-localize in human oligodendrocytes and in
differentiated HOG16 cells. The A2RE-like sequence of DDR1 contains
the single nucleotide polymorphism rs2267641, and we found that in
the human brain, the minor allele is associated with lower and higher
levels DDR1b and DDR1c mRNA expression, respectively. Moreover, a
positive correlation between DDR1c and the myelin genes myelin-associated
glycoprotein and oligodendrocyte lineage transcription factor 2 was
found. Differentiated HOG16 cells transfected with an hnRNP A2/B1
siRNA simultaneously show a decrease and an increase in the DDR1c
and DDR1b mRNA expression levels, respectively, which was accompanied
by a decrease in DDR1 protein levels at the cytoplasmic edges. These
results suggest that the DDR1 A2RE sequence is functionally involved
in the hnRNP A2/B1-mediated splicing and transport of the DDR1c mRNA.},
doi = {10.1111/j.1471-4159.2011.07580.x},
issn = {1471-4159},
keywords = {DDR1, hnRNP A2/B1, immunofluorescence, mRNA trafficking, oligodendrocytes,
SNP},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07580.x}
}
@ARTICLE{Roiniotis2009,
author = {Roiniotis, John and Dinh, Hang and Masendycz, Paul and Turner, Amanda
and Elsegood, Caryn L. and Scholz, Glen M. and Hamilton, John A.},
title = {Hypoxia Prolongs Monocyte/Macrophage Survival and Enhanced Glycolysis
Is Associated with Their Maturation under Aerobic Conditions},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {7974--7981},
number = {12},
month = jun,
abstract = {In chronic inflammatory lesions macrophages are abundant and adapt
to the low oxygen concentrations often present there. In low oxygen
some cell types die by apoptosis, as reported for macrophage cell
lines, while others survive better as they shift their metabolism
to anaerobic glycolysis. It was found here that hypoxia prolongs
the survival of murine bone marrow-derived macrophages, either in
the absence or presence of low CSF-1 (M-CSF) concentrations. Although
Akt activity increased in bone marrow-derived macrophages in the
low oxygen conditions, the levels of both anti- and proapoptotic
Bcl-2 family members decreased. Glycolysis was enhanced as judged
by increased glucose uptake, glucose transporter expression, lactate
dehydrogenase mRNA expression, and lactate secretion. Human monocytes
responded similarly to low oxygen, and a number of genes associated
with glycolysis were shown by microarray analysis and quantitative
PCR to be up-regulated. Interestingly, human monocyte-derived macrophages
showed evidence of enhanced glycolysis even under aerobic conditions.
It is proposed that certain monocyte/macrophage populations survive
better under conditions of low oxygen, thereby contributing to their
increased numbers at sites of chronic inflammation and tumors; it
is also proposed that as macrophages differentiate from monocytes
they begin to adopt a glycolytic metabolism allowing them to adapt
readily when exposed to low oxygen conditions.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/12/7974}
}
@ARTICLE{Roitbak2011,
author = {Roitbak, Tamara and Bragina, Olga and Padilla, Jamie and Pickett,
Gavin},
title = {The role of microRNAs in neural stem cell-supported endothelial morphogenesis},
journal = {Vascular Cell},
year = {2011},
volume = {3},
pages = {25},
number = {1},
abstract = {Functional signaling between neural stem/progenitor cells (NSPCs)
and brain endothelial cells (ECs) is essential to the coordination
of organized responses during initial embryonic development and also
during tissue repair, which occurs following brain injury. In this
study, we investigated the molecular mechanisms underlying this functional
signaling, using primary mouse brain ECs and NSPCs from embryonic
mouse brain. EC/NSPC co-culture experiments have revealed that neural
progenitors secrete factors supporting angiogenesis, which induce
noticeable changes in endothelial morphology. We demonstrate that
NSPCs influence the expression of mTOR and TGF-beta signaling pathway
components implicated in the regulation of angiogenesis. Endothelial
morphogenesis, an essential component of vascular development, is
a complex process involving gene activation and the upregulation
of specific cell signaling pathways. Recently identified small molecules,
called microRNAs (miRNAs), regulate the expression of genes and proteins
in many tissues, including brain and vasculature. We found that NSPCs
induced considerable changes in the expression of at least 24 miRNAs
and 13 genes in ECs. Three NSPC-regulated EC miRNAs were identified
as the potential primary mediators of this NSPC/EC interaction. We
found that the specific inhibition, or overexpression, of miRNAs
miR-155, miR-100, and miR-let-7i subsequently altered the expression
of major components of the mTOR, TGF-beta and IGF-1R signaling pathways
in ECs. Overexpression of these miRNAs in ECs suppressed, while inhibition
activated, the in vitro formation of capillary-like structures, a
process representative of EC morphogenesis. In addition, we demonstrate
that inhibition of FGF, VEGF, and TGF-beta receptor signaling abolished
NSPC-promoted changes in the endothelial miRNA profiles. Our findings
demonstrate that NSPCs induce changes in the miRNA expression of
ECs, which are capable of activating angiogenesis by modulating distinct
cell signaling pathways.},
doi = {10.1186/2045-824X-3-25},
issn = {2045-824X},
pubmedid = {22071092},
url = {http://www.vascularcell.com/content/3/1/25}
}
@ARTICLE{Rojas-Garcia2010,
author = {Rojas-Garcia, Pedro P. and Recabarren, Monica P. and Sarabia, Luis
and Schon, Jennifer and Gabler, Christoph and Einspanier, Ralf and
Maliqueo, Manuel and Sir-Petermann, Teresa and Rey, Rodolfo and Recabarren,
Sergio E.},
title = {Prenatal testosterone excess alters Sertoli and germ cell number
and testicular FSH receptor expression in rams},
journal = {Am J Physiol Endocrinol Metab},
year = {2010},
volume = {299},
pages = {E998--1005},
number = {6},
month = dec,
abstract = {Exposure to excess testosterone (T) during fetal life has a profound
impact on the metabolic and reproductive functions in the female's
postnatal life. However, less is known about the effects of excess
testosterone in males. The aim of the present study was to evaluate
the impact (consequences) of an excess of T during fetal development
on mature male testis. The testicular evaluation was by histological
analysis and by determination of mRNA expression of the FSH receptor
(FSH-R), transforming growth factor-{beta} type I receptor (T{beta}R-I),
and two members of the TGF-{beta} superfamily, transforming growth
factor-{beta}3 (TGF{beta}3) and anti-Mullerian hormone (AMH) in males
born to mothers receiving an excess of T during pregnancy. At 42
wk of age, postpubertal males born to mothers treated with 30 mg
of T propionate twice weekly from day 30 to 90, followed by 40 mg
of T propionate from day 90 to 120 of pregnancy (T males), showed
higher concentrations of FSH in response to a GnRH analog, a higher
number of Sertoli cells/seminiferous tubule cross-section, and a
lower number of germ cells/tubules (P < 0.05) than control males
(C males) born to mothers treated with the vehicle. The mRNA expression
of FSH-R and of T{beta}R-I was higher in T males compared with C
males (P < 0.05). Moreover, in T males, AMH expression level correlated
negatively with the expression level of TGF{beta}3. In C males, this
latter correlation was not observed. These results suggest that prenatal
exposure to an excess of T can negatively modify some histological
and molecular characteristics of the mature testis.},
comment = {10.1152/ajpendo.00032.2010},
url = {http://ajpendo.physiology.org/cgi/content/abstract/299/6/E998}
}
@ARTICLE{Rokitta2011,
author = {Rokitta, Sebastian D. and de Nooijer, Lennart J. and Trimborn, Scarlett
and de Vargas, Colomban and Rost, Björn and John, Uwe},
title = {Transcriptome analyses reveal differential gene expression patterns
between the life-cycle stages of emiliania huxleyi (haptophyta) and
reflect specialization to different ecological niches1},
journal = {Journal of Phycology},
year = {2011},
volume = {47},
pages = {829--838},
number = {4},
abstract = {Coccolithophores, especially the abundant, cosmopolitan species Emiliania
huxleyi (Lohmann) W. W. Hay et H. P. Mohler, are one of the main
driving forces of the oceanic carbonate pump and contribute significantly
to global carbon cycling, due to their ability to calcify. A recent
study indicates that termination of diploid blooms by viral infection
induces life-cycle transition, and speculation has arisen about the
role of the haploid, noncalcifying stage in coccolithophore ecology.
To explore gene expression patterns in both life-cycle stages, haploid
and diploid cells of E. huxleyi (RCC 1217 and RCC 1216) were acclimated
to limiting and saturating photon flux densities. Transcriptome analyses
were performed to assess differential genomic expression related
to different ploidy levels and acclimation light intensities. Analyses
indicated that life-cycle stages exhibit different properties of
regulating genome expression (e.g., pronounced gene activation and
gene silencing in the diploid stage), proteome maintenance (e.g.,
increased turnover of proteins in the haploid stage), as well as
metabolic processing (e.g., pronounced primary metabolism and motility
in the haploid stage and calcification in the diploid stage). Furthermore,
higher abundances of transcripts related to endocytotic and digestive
machinery were observed in the diploid stage. A qualitative feeding
experiment indicated that both life-cycle stages are capable of particle
uptake (0.5 μm diameter) in late-stationary growth phase. Results
showed that the two life-cycle stages represent functionally distinct
entities that are evolutionarily shaped to thrive in the environment
they typically inhabit.},
doi = {10.1111/j.1529-8817.2011.01014.x},
issn = {1529-8817},
keywords = {endocytosis, life-cycle stages, microarray, quantitative RT-PCR, transcriptome
profiling},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1529-8817.2011.01014.x}
}
@ARTICLE{Rokushima2008,
author = {Rokushima, Masatomo and Fujisawa, Kae and Furukawa, Naoko and Itoh,
Fumio and Yanagimoto, Toru and Fukushima, Ryou and Araki, Akiko and
Okada, Manabu and Torii, Mikinori and Kato, Ikuo and Ishizaki, Jun
and Omi, Kazuo},
title = {Transcriptomic Analysis of Nephrotoxicity Induced by Cephaloridine,
a Representative Cephalosporin Antibiotic},
journal = {Chemical Research in Toxicology},
year = {2008},
volume = {21},
pages = {1186-1196},
number = {6},
note = {PMID: 18500788},
doi = {10.1021/tx800008e},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx800008e},
url = {http://pubs.acs.org/doi/abs/10.1021/tx800008e}
}
@ARTICLE{Rokushima2007,
author = {Rokushima, Masatomo and Omi, Kazuo and Araki, Akiko and Kyokawa,
Yoshimasa and Furukawa, Naoko and Itoh, Fumio and Imura, Kae and
Takeuchi, Kumiko and Okada, Manabu and Kato, Ikuo and Ishizaki, Jun},
title = {A Toxicogenomic Approach Revealed Hepatic Gene Expression Changes
Mechanistically Linked to Drug-Induced Hemolytic Anemia},
journal = {Toxicol. Sci.},
year = {2007},
volume = {95},
pages = {474--484},
number = {2},
month = feb,
abstract = {A variety of pharmaceutical compounds causes hemolytic anemia as a
significant adverse effect and this toxicity restricts the clinical
utility of these drugs. In this study, we applied microarray technology
to investigate hepatic gene expression changes associated with drug-induced
hemolytic anemia and to identify potential biomarker genes for this
hematotoxicity. We treated female Sprague-Dawley rats with two hemolytic
anemia-inducing compounds: phenylhydrazine and phenacetin. Hepatic
gene expression profiles were obtained using a whole-genome oligonucleotide
microarray with pooled RNA samples from individual rats within each
dose group and analyzed in comparison with hepatic histopathology,
hematology, and blood chemistry data. We identified a small subset
of genes that were commonly deregulated in all the severe hemolytic
conditions, some of which were considered to be involved in hepatic
events characteristic of hemolytic anemia, such as hemoglobin biosynthesis,
heme metabolism, and phagocytosis. Among them, we selected six upregulated
genes as putative biomarkers, and their expression changes from microarray
measurements were confirmed by quantitative real-time PCR using RNAs
from individual animals. They were Alas2, beta-glo, Eraf, Hmox1,
Lgals3, and Rhced. Expression patterns of all these genes showed
high negative and positive correlation against erythrocyte counts
and total bilirubin levels in circulation, respectively, suggesting
that these genes may be the potential biomarkers for hemolytic anemia.
These findings indicate that drug-induced hemolytic anemia may be
detected based on hepatic changes in the expression of a subset of
genes that are mechanistically linked to the hematotoxicity.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/95/2/474}
}
@ARTICLE{Rokushima2007a,
author = {Rokushima, Masatomo and Omi, Kazuo and Imura, Kae and Araki, Akiko
and Furukawa, Naoko and Itoh, Fumio and Miyazaki, Masako and Yamamoto,
Junko and Rokushima, Makiko and Okada, Manabu and Torii, Mikinori
and Kato, Ikuo and Ishizaki, Jun},
title = {Toxicogenomics of Drug-Induced Hemolytic Anemia by Analyzing Gene
Expression Profiles in the Spleen},
journal = {Toxicol. Sci.},
year = {2007},
volume = {100},
pages = {290--302},
number = {1},
month = nov,
abstract = {Hemolytic anemia is a serious adverse effect of therapeutic drugs
that is caused by increased destruction of drug-damaged erythrocytes
by macrophages in the spleen and liver. We previously applied a toxicogenomic
approach to the toxicity by analyzing microarray data of the liver
of rats dosed with two hemolytic agents: phenylhydrazine and phenacetin.
In the present study, we analyzed gene expression profiles in the
spleen, the primary organ for destruction of damaged erythrocytes,
of the same models in order to identify splenic gene expression alterations
that could be used to predict the hematotoxicity. Microarray analyses
revealed hundreds of genes commonly deregulated under all severe
hemolytic conditions, which included genes related to splenic events
characteristic of the hematotoxicity, such as proteolysis and iron
metabolism. Eleven upregulated genes were selected as biomarker candidates,
and their expression changes were validated by quantitative real-time
PCR. The transcript levels of most of these genes showed strong correlation
with the results of classical toxicological assays (e.g., histopathology
and hematology). Furthermore, hierarchical clustering analysis suggested
that altered expression patterns of the 11 genes sensitively reflected
the erythrocyte damage even under a condition that caused no decrease
in erythrocyte counts. Among the selected genes, heme oxygenase 1
was one of the most promising biomarker candidates, the upregulation
of which on the protein level was confirmed by immunohistochemistry.
These results indicate that altered splenic expression of a subset
of genes may allow detection of drug-induced hemolytic anemia, with
better sensitivity than that of erythrocyte counts in the blood.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/100/1/290}
}
@ARTICLE{Roldan2011,
author = {Roldan, Mar and Macias-Gonzalez, Manuel and Garcia, Regina and Tinahones,
Francisco J. and Martin, Miguel},
title = {Obesity short-circuits stemness gene network in human adipose multipotent
stem cells},
journal = {FASEB J},
year = {2011},
volume = {25},
pages = {4111-4126},
number = {12},
abstract = {The discovery of adipose multipotent stem cells has provided new insights
to explore cellular mechanisms involved in adipose tissue function.
In the present work, we aimed to evaluate how the adipogenic environment
influences the stemness of the resident multipotent stem cells. To
achieve this goal, human omental multipotent stem cells (hO-MSCs)
were isolated, expanded, and characterized in both healthy lean and
morbidly obese individuals. We observed decreased cell proliferation,
premature senescence, and increased cytokine secretion associated
with increasing body mass index of the patients. Consistent with
the latter finding, the hO-MSCs derived from patients with morbid
obesity lose their multilineage differentiation capacity associated
with a dysregulation in the Wnt, Notch, and Sonic Hedgehog signaling
pathways. Moreover, microRNAs involved in the regulation of stemness,
cell differentiation, and senescence were also up-regulated in obese
individuals. Altogether, our data show that obesity causes a general
short circuit in the stemness gene network of hO-MSCs.--Roldan, M.,
Macias-Gonzalez, M., Garcia, R., Tinahones, F. J., Martin, M. Obesity
short-circuits stemness gene network in human adipose multipotent
stem cells.},
doi = {10.1096/fj.10-171439},
eprint = {http://www.fasebj.org/cgi/reprint/25/12/4111.pdf},
url = {http://www.fasebj.org/cgi/content/abstract/25/12/4111}
}
@ARTICLE{Roldo2006,
author = {Roldo, Claudia and Missiaglia, Edoardo and Hagan, John P. and Falconi,
Massimo and Capelli, Paola and Bersani, Samantha and Calin, George
Adrian and Volinia, Stefano and Liu, Chang-Gong and Scarpa, Aldo
and Croce, Carlo M.},
title = {MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar
Tumors Are Associated With Distinctive Pathologic Features and Clinical
Behavior},
journal = {J. Clin. Oncol.},
year = {2006},
volume = {24},
pages = {4677--4684},
number = {29},
month = oct,
abstract = {PURPOSE: We investigated the global microRNA expression patterns in
normal pancreas, pancreatic endocrine tumors and acinar carcinomas
to evaluate their involvement in transformation and malignant progression
of these tumor types. MicroRNAs are small noncoding RNAs that regulate
gene expression by targeting specific mRNAs for degradation or translation
inhibition. Recent evidence indicates that microRNAs can contribute
to tumor development and progression and may have diagnostic and
prognostic value in several human malignancies. MATERIALS AND METHODS:
Using a custom microarray, we studied the global microRNA expression
in 12 nontumor pancreas and 44 pancreatic primary tumors, including
12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar
carcinomas. RESULTS: Our data showed that a common pattern of microRNA
expression distinguishes any tumor type from normal pancreas, suggesting
that this set of microRNAs might be involved in pancreatic tumorigenesis;
the expression of miR-103 and miR-107, associated with lack of expression
of miR-155, discriminates tumors from normal; a set of 10 microRNAs
distinguishes endocrine from acinar tumors and is possibly associated
with either normal endocrine differentiation or endocrine tumorigenesis;
miR-204 is primarily expressed in insulinomas and correlates with
immunohistochemical expression of insulin; and the overexpression
of miR-21 is strongly associated with both a high Ki67 proliferation
index and presence of liver metastasis. CONCLUSION: These results
suggest that alteration in microRNA expression is related to endocrine
and acinar neoplastic transformation and progression of malignancy,
and might prove useful in distinguishing tumors with different clinical
behavior.},
url = {http://jco.ascopubs.org/cgi/content/abstract/24/29/4677}
}
@ARTICLE{Rolland2009,
author = {Rolland, Antoine and Lareyre, Jean-Jacques and Goupil, Anne-Sophie
and Montfort, Jérôme and Ricordel, Marie-Jo and Esquerré, Diane and
Hugot, Karine and Houlgatte, Rémi and Chalmel, Fréderic and Le Gac,
Florence},
title = {Expression profiling of rainbow trout testis development identifies
evolutionary conserved genes involved in spermatogenesis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {546},
number = {1},
abstract = {BACKGROUND:Spermatogenesis is a late developmental process that involves
a coordinated expression program in germ cells and a permanent communication
between the testicular somatic cells and the germ-line. Current knowledge
regarding molecular factors driving male germ cell proliferation
and differentiation in vertebrates is still limited and mainly based
on existing data from rodents and human. Fish with a marked reproductive
cycle and a germ cell development in synchronous cysts have proven
to be choice models to study precise stages of the spermatogenetic
development and the germ cell-somatic cell communication network.
In this study we used 9K cDNA microarrays to investigate the expression
profiles underlying testis maturation during the male reproductive
cycle of the trout, Oncorhynchus mykiss.RESULTS:Using total testis
samples at various developmental stages and isolated spermatogonia,
spermatocytes and spermatids, 3379 differentially expressed trout
cDNAs were identified and their gene activation or repression patterns
throughout the reproductive cycle were reported. We also performed
a tissue-profiling analysis and highlighted many genes for which
expression signals were restricted to the testes or gonads from both
sexes. The search for orthologous genes in genome-sequenced fish
species and the use of their mammalian orthologs allowed us to provide
accurate annotations for trout cDNAs. The analysis of the GeneOntology
terms therefore validated and broadened our interpretation of expression
clusters by highlighting enriched functions that are consistent with
known sequential events during male gametogenesis. Furthermore, we
compared expression profiles of trout and mouse orthologs and identified
a complement of genes for which expression during spermatogenesis
was maintained throughout evolution.CONCLUSION:A comprehensive study
of gene expression and associated functions during testis maturation
and germ cell differentiation in the rainbow trout is presented.
The study identifies new pathways involved during spermatogonia self-renewal
or rapid proliferation, meiosis and gamete differentiation, in fish
and potentially in all vertebrates. It also provides the necessary
basis to further investigate the hormonal and molecular networks
that trigger puberty and annual testicular recrudescence in seasonally
breeding species.},
doi = {10.1186/1471-2164-10-546},
issn = {1471-2164},
pubmedid = {19925684},
url = {http://www.biomedcentral.com/1471-2164/10/546}
}
@ARTICLE{Rolland2011,
author = {Rolland, Antoine D. and Lehmann, Kim P. and Johnson, Kamin J. and
Gaido, Kevin W. and Koopman, Peter},
title = {Uncovering Gene Regulatory Networks During Mouse Fetal Germ Cell
Development},
journal = {Biol Reprod},
year = {2011},
volume = {84},
pages = {790--800},
number = {4},
month = apr,
abstract = {The commitment of germ cells to either oogenesis or spermatogenesis
occurs during fetal gonad development: germ cells enter meiosis or
mitotic arrest, depending on whether they reside within an ovary
or a testis, respectively. Despite the critical importance of this
step for sexual reproduction, gene networks underlying germ cell
development have remained only partially understood. Taking advantage
of the Wv mouse model, in which gonads lack germ cells, we conducted
a microarray study to identify genes expressed in fetal germ cells.
In addition to distinguishing genes expressed by germ cells from
those expressed by somatic cells within the developing gonads, we
were able to highlight specific groups of genes expressed only in
female or male germ cells. Our results provide an important resource
for deciphering the molecular pathways driving proper germ cell development
and sex determination and will improve our understanding of the etiology
of human germ cell tumors that arise from dysregulation of germ cell
differentiation.},
comment = {10.1095/biolreprod.110.088443},
url = {http://www.biolreprod.org/cgi/content/abstract/84/4/790}
}
@ARTICLE{Rolland2009a,
author = {Rolland, Stephane and Bruel, Christophe and Rascle, Christine and
Girard, Vincent and Billon-Grand, Genevieve and Poussereau, Nathalie},
title = {pH controls both transcription and post-translational processing
of the protease BcACP1 in the phytopathogenic fungus Botrytis cinerea},
journal = {Microbiology},
year = {2009},
volume = {155},
pages = {2097--2105},
number = {6},
month = jun,
abstract = {During pathogenesis, the ascomycete Botrytis cinerea secretes a range
of cell-wall-degrading enzymes such as polygalacturonases, glucanases
and proteases. We report the identification of a new member of the
G1 family of proteases, BcACP1, which is secreted by B. cinerea during
infection. The production of BcACP1 correlates with the acidification
of the plant tissue, and transcriptional analysis of the Bcacp1 gene
showed that it is only expressed under acidic growth conditions.
Using a transcriptional reporter system, we showed that pH regulation
of Bcacp1 is not mediated by the canonical PacC transcription factor
binding site. Like other G1 proteases, BcACP1 is produced as a pro-enzyme.
Trapping of the zymogen form allowed investigation of its maturation
process. Evidence is presented for an autocatalytic proteolysis of
the enzyme that is triggered by acidic pH. Environmental pH therefore
controls Bcacp1 production at both the transcriptional and post-translational
level.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/155/6/2097}
}
@ARTICLE{Rollins2010,
author = {Rollins, Brandi and Martin, Maureen V. and Morgan, Ling and Vawter,
Marquis P.},
title = {Analysis of whole genome biomarker expression in blood and brain},
journal = {Am. J. Med. Genet.},
year = {2010},
volume = {153B},
pages = {919--936},
number = {4},
abstract = {Abstract 10.1002/ajmg.b.31062.abs The consistency of peripheral gene
expression data and the overlap with brain expression has not been
evaluated in biomarker discovery, nor has it been reported in multiple
tissues from the same subjects on a genome wide transcript level.
The effects of processing whole blood, transformation, and passaged
cell lines on gene expression profiling was studied in healthy subjects
using Affymetrix arrays. Ficoll extracted peripheral blood mononuclear
cells (PBMCs), Epstein–Barr virus (EBV) transformed lymphocytes,
passaged lymphoblastic cell lines (LCLs), and whole blood from Tempus
tubes were compared. There were 6,813 transcripts differentially
expressed between different methods of blood preparation. Principal
component analysis resolved two partitions involving pre- and post-transformation
EBV effects. Combining results from Affymetrix arrays, postmortem
subjects' brain and PBMC profiles showed co-expression levels of
summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts.
In a control experiment, rat hemi-brain and blood showed similar
expression levels for 19% of RefSeq transcripts. After filtering
transcripts that were not significantly different in abundance between
human cerebellum and PBMCs from the Affymetrix exon array the correlation
in mean transcript abundance was high as expected (r = 0.98).
Differences in the alternative splicing index in brain and blood
were found for about 90% of all transcripts examined. This study
demonstrates over 4,100 brain transcripts co-expressed in blood samples
can be further examined by in vitro and in vivo experimental studies
of blood and cell lines from patients with psychiatric disorders.
© 2010 Wiley-Liss, Inc.},
issn = {1552-485X},
keywords = {biomarker, gene expression, whole genome},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.31062}
}
@ARTICLE{Rolyan2011,
author = {Rolyan, Harshvardhan and Scheffold, Annika and Heinrich, Annette
and Begus-Nahrmann, Yvonne and Langkopf, Britta Heike and Holter,
Sabine M. and Vogt-Weisenhorn, Daniela M. and Liss, Birgit and Wurst,
Wolfgang and Lie, Dieter Chichung and Thal, Dietmar Rudolf and Biber,
Knut and Rudolph, Karl Lenhard},
title = {Telomere shortening reduces Alzheimer's disease amyloid pathology
in mice},
journal = {Brain},
year = {2011},
volume = {134},
pages = {2044-2056},
number = {7},
abstract = {Alzheimer's disease is a neurodegenerative disorder of the elderly
and advancing age is the major risk factor for Alzheimer's disease
development. Telomere shortening represents one of the molecular
causes of ageing that limits the proliferative capacity of cells,
including neural stem cells. Studies on telomere lengths in patients
with Alzheimer's disease have revealed contrary results and the functional
role of telomere shortening on brain ageing and Alzheimer's disease
is not known. Here, we have investigated the effects of telomere
shortening on adult neurogenesis and Alzheimer's disease progression
in mice. The study shows that aged telomerase knockout mice with
short telomeres (G3Terc-/-) exhibit reduced dentate gyrus neurogenesis
and loss of neurons in hippocampus and frontal cortex, associated
with short-term memory deficit in comparison to mice with long telomere
reserves (Terc+/+). In contrast, telomere shortening improved the
spatial learning ability of ageing APP23 transgenic mice, a mouse
model for Alzheimer's disease. Telomere shortening was also associated
with an activation of microglia in ageing amyloid-free brain. However,
in APP23 transgenic mice, telomere shortening reduced both amyloid
plaque pathology and reactive microgliosis. Together, these results
provide the first experimental evidence that telomere shortening,
despite impairing adult neurogenesis and maintenance of post-mitotic
neurons, can slow down the progression of amyloid plaque pathology
in Alzheimer's disease, possibly involving telomere-dependent effects
on microglia activation.},
doi = {10.1093/brain/awr133},
eprint = {http://brain.oxfordjournals.org/cgi/reprint/134/7/2044.pdf},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/134/7/2044}
}
@ARTICLE{Rom2009,
author = {Rom, J. and von Minckwitz, G. and Marme, F. and Ataseven, B. and
Kozian, D. and Sievert, M. and Schlehe, B. and Schuetz, F. and Scharf,
A. and Kaufmann, M. and Sohn, C. and Schneeweiss, A.},
title = {Phase I study of apoptosis gene modulation with oblimersen within
preoperative chemotherapy in patients with primary breast cancer},
journal = {Ann. Onc.},
year = {2009},
volume = {20},
pages = {1829--1835},
number = {11},
month = nov,
abstract = {Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated
apoptotic signals in patients with breast cancer. We investigated
effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide
oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 messenger
RNA (mRNA), down-regulates Bcl-2 protein translation and enhances
antitumor effects of subtherapeutic chemotherapy doses. Within a
phase I trial, we administered escalating doses of oblimersen (3,
5 or 7 mg/kg/day) as continuous infusion on days 1-7 in combination
with standard-dose docetaxel (Taxotere), Adriamycin and cyclophosphamide
(TAC) on day 5 as preoperative chemotherapy in 28 patients with T2-4
tumors. Effects of oblimersen were evaluated in tumor biopsies and
peripheral blood mononuclear cells (PBMCs) 4 days after start of
oblimersen and before TAC treatment by quantitative microfluidic
real-time PCR. Read-outs consisted in measurement of Bcl-2 mRNA modulations
and of 18 putative predictive markers. Two of 13 patients showed
a diminution of Bcl-2 transcripts after 4 days of treatment with
oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate
tissue because no qualified RNA could be isolated. Nevertheless,
we demonstrated feasibility to process clinical samples and to obtain
good quality RNA from tumor biopsies and indicated the potential
of oblimersen to lower Bcl-2 mRNA in breast cancer.},
url = {http://annonc.oxfordjournals.org/cgi/content/abstract/20/11/1829}
}
@ARTICLE{Romagnoli2009,
author = {Romagnoli, Mathilde and Séveno, Céline and Wuillème-Toumi, Soraya
and Amiot, Martine and Bataille, Régis and Minvielle, Stéphane
and Barillé-Nion, Sophie},
title = {The imbalance between Survivin and Bim mediates tumour growth and
correlates with poor survival in patients with multiple myeloma},
journal = {British Journal of Haematology},
year = {2009},
volume = {145},
pages = {180--189},
number = {2},
abstract = {Summary Survivin is selectively expressed in most of common human
cancers and is now viewed as a potent modulator of the cell death/proliferation
balance in tumour cells. We previously found that myeloma cells expressed
high levels of Survivin protein in correlation with disease progression
and that Survivin knock-down by RNA interference decreased myeloma
cell growth. We now demonstrate that Survivin overexpression promotes
the proliferation and survival of human myeloma cells both in vitro
and in vivo in the absence of their major growth factor, interleukin
6. Of particular interest, this effect correlates with the down regulation
of Bim, a critical BH3-only cell death activator during cytokine
deprivation, mainly at transcriptional level. The tight link between
Survivin and Bim expression, reported for the first time here in
myeloma cells and in other cell lines, is further confirmed in a
panel of newly diagnosed patients with myeloma, and BIRC5 is validated
as a gene significantly associated with short survival in these patients.
Altogether, our findings provide evidence that Survivin directly
contributes to malignant progression of myeloma and strongly suggest
that targeting Survivin may disrupt the delicate balance controlling
cell survival and proliferation, opening new avenues for the therapy
of this still difficult-to-treat cancer.},
issn = {1365-2141},
keywords = {myeloma, Survivin, Bim, apoptosis, tumour growth},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2009.07608.x}
}
@ARTICLE{Romano2010,
author = {Romano, Rose-Anne and Smalley, Kirsten and Liu, Song and Sinha, Satrajit},
title = {Abnormal hair follicle development and altered cell fate of follicular
keratinocytes in transgenic mice expressing {Delta}Np63{alpha}},
journal = {Development},
year = {2010},
volume = {137},
pages = {1431--1439},
number = {9},
month = may,
abstract = {The transcription factor p63 plays an essential role in epidermal
morphogenesis. Animals lacking p63 fail to form many ectodermal organs,
including the skin and hair follicles. Although the indispensable
role of p63 in stratified epithelial skin development is well established,
relatively little is known about this transcriptional regulator in
directing hair follicle morphogenesis. Here, using specific antibodies,
we have established the expression pattern of {Delta}Np63 in hair
follicle development and cycling. {Delta}Np63 is expressed in the
developing hair placode, whereas in mature hair its expression is
restricted to the outer root sheath (ORS), matrix cells and to the
stem cells of the hair follicle bulge. To investigate the role of
{Delta}Np63 in hair follicle morphogenesis and cycling, we have utilized
a Tet-inducible mouse model system with targeted expression of this
isoform to the ORS of the hair follicle. {Delta}Np63 transgenic animals
display dramatic defects in hair follicle development and cycling,
eventually leading to severe hair loss. Strikingly, expression of
{Delta}Np63 leads to a switch in cell fate of hair follicle keratinocytes,
causing them to adopt an interfollicular epidermal (IFE) cell identity.
Moreover, {Delta}Np63 transgenic animals exhibit a depleted hair
follicle stem-cell niche, which further contributes to the overall
cycling defects observed in the mutant animals. Finally, global transcriptome
analysis of transgenic skin identified altered expression levels
of crucial mediators of hair morphogenesis, including key members
of the Wnt/{beta}-catenin signaling pathway, which, in part, account
for these effects. Our data provide evidence supporting a role for
{Delta}Np63{alpha} in actively suppressing hair follicle differentiation
and directing IFE cell lineage commitment.},
url = {http://dev.biologists.org/cgi/content/abstract/137/9/1431}
}
@ARTICLE{Romanoski2010,
author = {Romanoski, Casey E. and Lee, Sangderk and Kim, Michelle J. and Ingram-Drake,
Leslie and Plaisier, Christopher L. and Yordanova, Roumyana and Tilford,
Charles and Guan, Bo and He, Aiqing and Gargalovic, Peter S. and
Kirchgessner, Todd G. and Berliner, Judith A. and Lusis, Aldons J.},
title = {Systems Genetics Analysis of Gene-by-Environment Interactions in
Human Cells},
journal = {The American Journal of Human Genetics},
year = {2010},
volume = {86},
pages = {399--410},
number = {3},
month = mar,
abstract = {Gene by environment (GxE) interactions are clearly important in many
human diseases, but they have proven to be difficult to study on
a molecular level. We report genetic analysis of thousands of transcript
abundance traits in human primary endothelial cell (EC) lines in
response to proinflammatory oxidized phospholipids implicated in
cardiovascular disease. Of the 59 most regulated transcripts, approximately
one-third showed evidence of GxE interactions. The interactions resulted
primarily from effects of distal-, trans-acting loci, but a striking
example of a local-GxE interaction was also observed for FGD6. Some
of the distal interactions were validated by siRNA knockdown experiments,
including a locus involved in the regulation of multiple transcripts
involved in the ER stress pathway. Our findings add to the understanding
of the overall architecture of complex human traits and are consistent
with the possibility that GxE interactions are responsible, in part,
for the failure of association studies to more fully explain common
disease variation.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4YDS2GW-5/2/421abbc0ae485097cfff5277efee3eb5}
}
@ARTICLE{Romanuik2009,
author = {Romanuik, Tammy and Wang, Gang and Holt, Robert and Jones, Steven
and Marra, Marco and Sadar, Marianne},
title = {Identification of novel androgen-responsive genes by sequencing of
LongSAGE libraries},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {476},
number = {1},
abstract = {BACKGROUND:The development and maintenance of the prostate is dependent
on androgens and the androgen receptor. The androgen pathway continues
to be important in prostate cancer. Here, we evaluated the transcriptome
of prostate cancer cells in response to androgen using long serial
analysis of gene expression (LongSAGE) libraries.RESULTS:There were
131 tags (87 genes) that displayed statistically significant (p =
0.001) differences in expression in response to androgen. Many of
the genes identified by LongSAGE (35/87) have not been previously
reported to change expression in the direction or sense observed.
In regulatory regions of the promoter and/or enhancer regions of
some of these genes there are confirmed or potential androgen response
elements (AREs). The expression trends of 24 novel genes were validated
using quantitative real time-polymerase chain reaction (qRT-PCR).
These genes were: ARL6IP5, BLVRB, C19orf48, C1orf122, C6orf66, CAMK2N1,
CCNI, DERA, ERRFI1, GLUL, GOLPH3, HM13, HSP90B1, MANEA, NANS, NIPSNAP3A,
SLC41A1, SOD1, SVIP, TAOK3, TCP1, TMEM66, USP33, and VTA1. The physiological
relevance of these expression trends was evaluated in vivo using
the LNCaP Hollow Fibre model. Novel androgen-responsive genes identified
here participate in protein synthesis and trafficking, response to
oxidative stress, transcription, proliferation, apoptosis, and differentiation.CONCLUSION:These
processes may represent the molecular mechanisms of androgen-dependency
of the prostate. Genes that participate in these pathways may be
targets for therapies or biomarkers of prostate cancer.},
doi = {10.1186/1471-2164-10-476},
issn = {1471-2164},
pubmedid = {19832994},
url = {http://www.biomedcentral.com/1471-2164/10/476}
}
@ARTICLE{Romanuik2010,
author = {Romanuik, Tammy and Wang, Gang and Morozova, Olena and Delaney, Allen
and Marra, Marco and Sadar, Marianne},
title = {LNCaP Atlas: Gene expression associated with in vivo progression
to castration-recurrent prostate cancer},
journal = {BMC Medical Genomics},
year = {2010},
volume = {3},
pages = {43},
number = {1},
abstract = {BACKGROUND:There is no cure for castration-recurrent prostate cancer
(CRPC) and the mechanisms underlying this stage of the disease are
unknown.METHODS:We analyzed the transcriptome of human LNCaP prostate
cancer cells as they progress to CRPC in vivo using replicate LongSAGE
libraries. We refer to these libraries as the LNCaP atlas and compared
these gene expression profiles with current suggested models of CRPC.RESULTS:Three
million tags were sequenced using in vivo samples at various stages
of hormonal progression to reveal 96 novel genes differentially expressed
in CRPC. Thirty-one genes encode proteins that are either secreted
or are located at the plasma membrane, 21 genes changed levels of
expression in response to androgen, and 8 genes have enriched expression
in the prostate. Expression of 26, 6, 12, and 15 genes have previously
been linked to prostate cancer, Gleason grade, progression, and metastasis,
respectively. Expression profiles of genes in CRPC support a role
for the transcriptional activity of the androgen receptor (CCNH,
CUEDC2, FLNA, PSMA7), steroid synthesis and metabolism (DHCR24, DHRS7,
ELOVL5, HSD17B4, OPRK1), neuroendocrine (ENO2, MAOA, OPRK1, S100A10,
TRPM8), and proliferation (GAS5, GNB2L1, MT-ND3, NKX3-1, PCGEM1,
PTGFR, STEAP1, TMEM30A), but neither supported nor discounted a role
for cell survival genes.CONCLUSIONS:The in vivo gene expression atlas
for LNCaP was sequenced and support a role for the androgen receptor
in CRPC.},
doi = {10.1186/1755-8794-3-43},
issn = {1755-8794},
pubmedid = {20868494},
url = {http://www.biomedcentral.com/1755-8794/3/43}
}
@ARTICLE{Romanuik2009a,
author = {Romanuik, Tammy L. and Ueda, Takeshi and Le, Nhu and Haile, Simon
and Yong, Theresa M.K. and Thomson, Thomas and Vessella, Robert L.
and Sadar, Marianne D.},
title = {Novel Biomarkers for Prostate Cancer Including Noncoding Transcripts},
journal = {Am. J. Pathol.},
year = {2009},
volume = {175},
pages = {2264--2276},
number = {6},
month = dec,
abstract = {Levels of 27 transcripts were investigated as potential novel markers
for prostate cancer, including genes encoding plasma membrane proteins
(ADAM2, ELOVL5, MARCKSL1, RAMP1, TMEM30A, and TMEM66); secreted proteins
(SPON2, TMEM30A, TMEM66, and truncated TMEFF2 (called POP4)); intracellular
proteins (CAMK2N1, DHCR24, GLO1, NGFRAP1, PGK1, PSMA7, SBDS, and
YWHAQ); and noncoding transcripts (POP1 (100 kb) from mRNA AK000023),
POP2 (4 kb from mRNA AL832227), POP3 (50 kb from EST CFI40309), POP5
(intron of NCAM2, accession DO668384), POP6 (intron of FHIT), POP7
(intron of TNFAIP8), POP8 (intron of EFNA5), POP9 (intron of DSTN),
POP10 (intron of ADAM2, accession DO668396), POP11 (87kb from EST
BG194644), and POP12 (intron of EST BQ226050)). Expression of POP3
was prostate specific, whereas ADAM2, POP1, POP4, POP10, ELOVL5,
RAMP1, and SPON2 had limited tissue expression. ELOVL5, MARCKSL1,
NGFRAP1, PGK1, POP2, POP5, POP8, PSMA7, RAMP1, and SPON2 were significantly
differentially expressed between laser microdissected malignant versus
benign clinical samples of prostate tissue. PGK1, POP2, and POP12
correlated to clinical parameters. Levels of CAMK2N1, GLO1, SDBS,
and TMEM30A transcripts tended to be increased in primary prostate
cancer from patients who later had biochemical failure. Expression
of GLO1, DHCR24, NGFRAP1, KLK3, and RAMP1 were significantly decreased
in metastatic castration-recurrent disease compared with androgen-dependent
primary prostate cancer. These novel potential biomarkers may therefore
be useful in the diagnosis/prognosis of prostate cancer.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/175/6/2264}
}
@ARTICLE{Rome2003,
author = {Rome, Sophie and Clement, Karine and Rabasa-Lhoret, Remi and Loizon,
Emmanuelle and Poitou, Christine and Barsh, Greg S. and Riou, Jean-Paul
and Laville, Martine and Vidal, Hubert},
title = {Microarray Profiling of Human Skeletal Muscle Reveals That Insulin
Regulates ~800 Genes during a Hyperinsulinemic Clamp},
journal = {J. Biol. Chem.},
year = {2003},
volume = {278},
pages = {18063--18068},
number = {20},
month = may,
abstract = {Insulin action in target tissues involved precise regulation of gene
expression. To define the set of insulin-regulated genes in human
skeletal muscle, we analyzed the global changes in mRNA levels during
a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle
of six healthy subjects. Using 29,308 cDNA element microarrays, we
found that the mRNA expression of 762 genes, including 353 expressed
sequence tags, was significantly modified during insulin infusion.
478 were up-regulated and 284 down-regulated. Most of the genes with
known function are novel targets of insulin. They are involved in
the transcriptional and translational regulation (29%), intermediary
and energy metabolisms (14%), intracellular signaling (12%), and
cytoskeleton and vesicle traffic (9%). Other categories consisted
of genes coding for receptors, carriers, and transporters (8%), components
of the ubiquitin/proteasome pathways (7%) and elements of the immune
response (5.5%). These results thus define a transcriptional signature
of insulin action in human skeletal muscle. They will help to better
define the mechanisms involved in the reduction of insulin effectiveness
in pathologies such as type 2 diabetes mellitus, a disease characterized
by defective regulation of gene expression in response to insulin.},
url = {http://www.jbc.org/cgi/content/abstract/278/20/18063}
}
@ARTICLE{Rome2008,
author = {Rome, Sophie and Lecomte, Virginie and Meugnier, Emmanuelle and Rieusset,
Jennifer and Debard, Cyrille and Euthine, Vanessa and Vidal, Hubert
and Lefai, Etienne},
title = {Microarray analyses of SREBP-1a and SREBP-1c target genes identify
new regulatory pathways in muscle},
journal = {Physiol Genomics},
year = {2008},
volume = {34},
pages = {327--337},
number = {3},
month = aug,
abstract = {In this study we have identified the target genes of sterol regulatory
element binding protein (SREBP)-1a and SREBP-1c in primary cultures
of human skeletal muscle cells, using adenoviral vectors expressing
the mature nuclear form of human SREBP-1a or SREBP-1c combined with
oligonucleotide microarrays. Overexpression of SREBP-1a led to significant
changes in the expression of 1,315 genes (655 upregulated and 660
downregulated), whereas overexpression of SREBP-1c modified the mRNA
level of 514 genes (310 upregulated and 204 downregulated). Gene
ontology analysis indicated that in human muscle cells SREBP-1a and
-1c are involved in the regulation of a large number of genes that
are at the crossroads of different functional pathways, several of
which are not directly connected with cholesterol and lipid metabolism.
Six hundred fifty-two of all genes identified to be differentially
regulated on SREBP overexpression had a sterol regulatory element
(SRE) motif in their promoter sequences. Among these, 429 were specifically
regulated by SREBP-1a, 69 by SREBP-1c, and 154 by both 1a and 1c.
Because both isoforms recognize the same binding motif, we determined
whether some of these functional differences could depend on the
environment of the SRE motifs in the promoters. Results from promoter
analysis showed that different combinations of transcription factor
binding sites around the SRE binding motifs may determine regulatory
networks of transcription that could explain the superposition of
lipid and cholesterol metabolism with various other pathways involved
in adaptive responses to stress like hypoxia and heat shock, or involvement
in the immune response.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/34/3/327}
}
@ARTICLE{Romero2011,
author = {Atocha Romero and Miguel MartÃn and Maggie C.U. Cheang and José
Antonio López GarcÃa-Asenjo and Belén Oliva and Xiaping He and
Miguel de la Hoya and Jose Ã?ngel GarcÃa Sáenz and Manuel Arroyo
Fernández and Eduardo DÃaz Rubio and Charles M. Perou and Trinidad
Caldés Llopis},
title = {Assessment of Topoisomerase II α Status in Breast Cancer by Quantitative
PCR, Gene Expression Microarrays, Immunohistochemistry, and Fluorescence
in Situ Hybridization},
journal = {The American Journal of Pathology},
year = {2011},
volume = {178},
pages = {1453 - 1460},
number = {4},
abstract = {Anthracyclines are frequently used for the treatment of breast cancer
and topoisomerase II alpha (TOP2A) is considered to be the molecular
target. Numerous studies have evaluated the predictive value of TOP2A
using different methodological approaches and inconsistent results
have been reported. Indeed, the correlation between techniques for
the assessment of TOP2A status has not been well evaluated. In this
study, we determined TOP2A status in 61 breast tumor samples by real-time
PCR, DNA microarrays, immunohistochemistry (IHC), and fluorescence
in situ hybridization (FISH), and then evaluated these results with
clinical-pathological features and breast cancer intrinsic subtypes.
First, we observed a statistical significant correlation of TOP2A
gene expression between real-time PCR and microarrays (Pearson coefficient,
0.816; P < 0.001), and both predicted TOP2A IHC results fairly
well (area under the curve > 0.74). In contrast, poor agreement
between FISH and IHC data was observed (k: 0.134). Secondly, TOP2A
expression was found significantly associated with cell proliferation,
and with the highly proliferative Luminal B, Her2-enriched and Basal-like
intrinsic subtypes. In conclusion, TOP2A expression in breast cancer
was associated with high proliferation and aggressive tumor subtypes
and appears to be independent of its amplification status. All of
these features should be taken into consideration when assessing
the predictive value of TOP2A for anthracycline-based chemotherapy.},
doi = {10.1016/j.ajpath.2010.12.042},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011000423}
}
@ARTICLE{Romero2011a,
author = {Romero, Atocha and Martín, Miguel and Cheang, Maggie C.U. and López
García-Asenjo, José Antonio and Oliva, Belén and He, Xiaping and
de la Hoya, Miguel and García Sáenz, Jose Ángel and Arroyo Fernández,
Manuel and Díaz Rubio, Eduardo and Perou, Charles M. and Llopis,
Trinidad Caldés},
title = {Assessment of Topoisomerase II [alpha] Status in Breast Cancer by
Quantitative PCR, Gene Expression Microarrays, Immunohistochemistry,
and Fluorescence in Situ Hybridization},
journal = {The American Journal of Pathology},
year = {2011},
volume = {178},
pages = {1453--1460},
number = {4},
month = apr,
abstract = {Anthracyclines are frequently used for the treatment of breast cancer
and topoisomerase II alpha (TOP2A) is considered to be the molecular
target. Numerous studies have evaluated the predictive value of TOP2A
using different methodological approaches and inconsistent results
have been reported. Indeed, the correlation between techniques for
the assessment of TOP2A status has not been well evaluated. In this
study, we determined TOP2A status in 61 breast tumor samples by real-time
PCR, DNA microarrays, immunohistochemistry (IHC), and fluorescence
in situ hybridization (FISH), and then evaluated these results with
clinical-pathological features and breast cancer intrinsic subtypes.
First, we observed a statistical significant correlation of TOP2A
gene expression between real-time PCR and microarrays (Pearson coefficient,
0.816; P < 0.001), and both predicted TOP2A IHC results fairly well
(area under the curve > 0.74). In contrast, poor agreement between
FISH and IHC data was observed (k: 0.134). Secondly, TOP2A expression
was found significantly associated with cell proliferation, and with
the highly proliferative Luminal B, Her2-enriched and Basal-like
intrinsic subtypes. In conclusion, TOP2A expression in breast cancer
was associated with high proliferation and aggressive tumor subtypes
and appears to be independent of its amplification status. All of
these features should be taken into consideration when assessing
the predictive value of TOP2A for anthracycline-based chemotherapy.},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011000423}
}
@ARTICLE{Romieu-Mourez2006,
author = {Romieu-Mourez, Raphaelle and Solis, Mayra and Nardin, Alessandra
and Goubau, Delphine and Baron-Bodo, Veronique and Lin, Rongtuan
and Massie, Bernard and Salcedo, Margarita and Hiscott, John},
title = {Distinct Roles for IFN Regulatory Factor (IRF)-3 and IRF-7 in the
Activation of Antitumor Properties of Human Macrophages},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {10576--10585},
number = {21},
month = nov,
abstract = {When properly activated, macrophages can be tumoricidal, thus making
them attractive additions to standard cancer therapies. To this end,
tolerance and activity of human autologous IFN-{gamma}-activated
macrophages, produced in large scale for clinical use (MAK cells),
have been assessed in pilot trials in cancer patients. In the present
study, we tested the hypothesis that activation of IFN regulatory
factor (IRF)-3 and IRF-7, with subsequent type I IFN production,
may be involved in the acquisition of new antitumor functions by
macrophages. Adenoviral vectors were generated for the delivery of
constitutively active forms of IRF-3 (Ad-IRF-3) or IRF-7 (Ad-IRF-7)
into primary human macrophages. Cell death was observed in Ad-IRF-3-transduced
macrophages, whereas Ad-IRF-7-transduced macrophages produced type
I IFNs and displayed increased expression of genes encoding tumor
necrosis factor (TNF)-related apoptosis-inducing ligand, interleukin
(IL)-12, IL-15, and CD80, persisting for at least 96 hours. Expression
of iNOS, TNF-{alpha}, FasL, IL-1, and IL-6 genes was unaltered by
Ad-IRF-7 transduction. Interestingly, Ad-IRF-3 or Ad-IRF-7 transduction
negatively regulated the transcription of protumorigenic genes encoding
vascular endothelial growth factor and matrix metalloproteinase-2.
Furthermore, Ad-IRF-7-transduced macrophages exerted a cytostatic
activity on different cancer cell lines, including SK-BR-3, MCF-7,
and COLO-205; the latter cells were shown previously to be insensitive
to MAK cells. In conclusion, transduction of active forms of IRF-3
or IRF-7 differentially modulate the apoptotic and antitumor properties
of primary macrophages, with active IRF-7 leading to the acquisition
of novel antitumor effector functions. (Cancer Res 2006; 66(21):
10576-85)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/21/10576}
}
@ARTICLE{Romito-DiGiacomo2007,
author = {Romito-DiGiacomo, Rita R. and Menegay, Harry and Cicero, Samantha
A. and Herrup, Karl},
title = {Effects of Alzheimer's Disease on Different Cortical Layers: The
Role of Intrinsic Differences in A{beta} Susceptibility},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {8496--8504},
number = {32},
month = aug,
abstract = {Alzheimer's disease is late life dementia associated with significant
neurodegeneration in both cortical and subcortical regions. During
the [~]10 year course of the disease, neurons are lost in a progressive
pattern that is relatively consistent among individuals. One example
of this is the progression of disease pathology found in both the
neocortex and archicortex. In these structures, the earliest problems
can be found in superficial cortical layers (II-IV), whereas later
the disease advances to involve the deeper cortical layers (V-VI).
It is unclear whether these apparent differences in sensitivity are
intrinsic to the neurons or imposed by external factors such as the
pattern of connections. We used {beta}-amyloid (A{beta}) peptide
treatment of cultured mouse neurons as our model system. We show
first that, as in hippocampus, dissociated cultures of embryonic
cortical neurons are biased toward the survival of cells that were
finishing division in the ventricular zone at the time of harvest.
Thus, embryonic day 13.5 (E13.5) cultures contain primarily deep-layer
neurons whereas E16.5 cultures contain cells destined for upper layers.
We use this cell-type specific segregation to our advantage and show,
using both differences in gene expression profiles and A{beta} survival
curves, that deeper layer neurons are significantly more resistant
to the toxic effects of A{beta} than are cells from the more superficial
strata. This suggests that an intrinsic underlying biology drives
at least part of the AD progression pattern and that the time of
harvest is a crucial variable in the interpretation of any cortical
culture experiment.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/32/8496}
}
@ARTICLE{Rondinone2002,
author = {Rondinone, Cristina M. and Trevillyan, James M. and Clampit, Jill
and Gum, Rebecca J. and Berg, Cathy and Kroeger, Paul and Frost,
Leigh and Zinker, Bradley A. and Reilly, Regina and Ulrich, Roger
and Butler, Madeline and Monia, Brett P. and Jirousek, Michael R.
and Waring, Jeffrey F.},
title = {Protein Tyrosine Phosphatase 1B Reduction Regulates Adiposity and
Expression of Genes Involved in Lipogenesis},
journal = {Diabetes},
year = {2002},
volume = {51},
pages = {2405--2411},
number = {8},
month = aug,
abstract = {Protein tyrosine phosphatase 1B (PTP1B) has been implicated as a negative
regulator of insulin action. Overexpression of PTP1B protein has
been observed in insulin-resistant states associated with obesity.
Mice lacking a functional PTP1B gene exhibit increased insulin sensitivity
and are resistant to weight gain. To investigate the role of PTP1B
in adipose tissue from obese animals, hyperglycemic obese (ob/ob)
mice were treated with PTP1B antisense oligonucleotide (ISIS-113715).
A significant reduction in adiposity correlated with a decrease of
PTP1B protein levels in fat. Antisense treatment also influenced
the triglyceride content in adipocytes, correlating with a downregulation
of genes encoding proteins involved in lipogenesis, such as sterol
regulatory element-binding protein 1 and their downstream targets
spot14 and fatty acid synthase, as well as other adipogenic genes,
lipoprotein lipase, and peroxisome proliferator-activated receptor
{gamma}. In addition, an increase in insulin receptor substrate-2
protein and a differential regulation of the phosphatidylinositol
3-kinase regulatory subunit (p85{alpha}) isoforms expression were
found in fat from antisense-treated animals, although increased insulin
sensitivity measured by protein kinase B phosphorylation was not
observed. These results demonstrate that PTP1B antisense treatment
can modulate fat storage and lipogenesis in adipose tissue and might
implicate PTP1B in the enlargement of adipocyte energy stores and
development of obesity.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/51/8/2405}
}
@ARTICLE{Rong2007,
author = {Rong, Jianhui and Tilton, Robert and Shen, Jiangang and Ng, Kwan-Ming
and Liu, Chang and Tam, Paul Kwong-Hang and Lau, Allan Sik-Yin and
Cheng, Yung-Chi},
title = {Genome-wide biological response fingerprinting (BioReF) of the Chinese
botanical formulation ISF-1 enables the selection of multiple marker
genes as a potential metric for quality control},
journal = {Journal of Ethnopharmacology},
year = {2007},
volume = {113},
pages = {35--44},
number = {1},
month = aug,
abstract = {Quality control plays a critical role in the process of translating
the traditional/alternative medicines into modern evidence-based
therapies. High performance liquid chromatography (HPLC) is widely
applied to assess the chemical composition of botanical drug products.
The chromatographic fingerprints or chemical profiles are currently
used as the de facto quality control metric. As a complement to chemical
profiles, a biological quality control assessment offers distinct
advantages. This study describes a genome-wide biological response
fingerprinting (BioReF) approach to define a set of marker genes
that define a signature pattern for a specific botanical formulation.
These marker genes are chosen on the basis of the levels of the regulated
expression and the involvement in the cellular signaling pathways.
Subsequently, qRT-PCR technique is used to simultaneously monitor
the gene expression of multiple marker genes in an efficient and
quantitative manner. This set of marker genes represents the biological
responses of human cells to the chemical composition of the botanical
drug that could serve as potential quality control of botanical drugs
in terms of the consistency of biological activities. We demonstrate
the BioReF approach with a well-documented Chinese Medicine formula,
designated as ISF-1, traditionally used for the management of post-stroke
disorders. A set of nine marker genes were selected to assess the
batch-to-batch consistency of the biological effects of ISF-1. This
approach provides a potential comprehensive and cost-effective quality
control metric of the biological activities of botanical drugs.},
issn = {0378-8741},
keywords = {Botanical drug products, Traditional Chinese medicine, Quality control,
Biological response fingerprinting, DNA microarray, qRT-PCR},
url = {http://www.sciencedirect.com/science/article/B6T8D-4MVVSPM-3/2/75264dcb6f07dd3431071d5da7c72163}
}
@ARTICLE{Ronnberg2010,
author = {Ronnberg, Elin and Guss, Bengt and Pejler, Gunnar},
title = {Infection of Mast Cells with Live Streptococci Causes a Toll-Like
Receptor 2- and Cell-Cell Contact-Dependent Cytokine and Chemokine
Response},
journal = {Infect. Immun.},
year = {2010},
volume = {78},
pages = {854--864},
number = {2},
month = feb,
abstract = {Mast cells (MCs) are strongly implicated in immunity toward bacterial
infection, but the molecular mechanisms by which MCs contribute to
the host response are only partially understood. We addressed this
issue by examining the direct effects of a Gram-positive pathogen,
Streptococcus equi, on bone marrow-derived MCs (BMMCs). Ultrastructural
analysis revealed extensive formation of dilated rough endoplasmic
reticulum in response to bacterial infection, indicating strong induction
of protein synthesis. However, the BMMCs did not show signs of extensive
degranulation, and this was supported by only slow release of histamine
in response to infection. Coculture of live bacteria with BMMCs caused
a profound secretion of CCL2/MCP-1, CCL7/MCP-3, CXCL2/MIP-2, CCL5/RANTES,
interleukin-4 (IL-4), IL-6, IL-12, IL-13, and tumor necrosis factor
alpha, as shown by antibody-based cytokine/chemokine arrays and/or
enzyme-linked immunosorbent assay. In contrast, heat-inactivated
bacteria caused only minimal cytokine/chemokine release. The cytokine/chemokine
responses were substantially attenuated in Toll-like receptor 2-deficient
BMMCs and were strongly dependent on cell-cell contacts between bacteria
and BMMCs. Gene chip microarray analysis confirmed a massively upregulated
expression of the genes coding for the secreted cytokines and chemokines
and also identified a pronounced upregulation of numerous additional
genes, including transcription factors, signaling molecules, and
proteases. Together, the present study outlines MC-dependent molecular
events associated with Gram-positive infection and thus provides
an advancement in our understanding of how MCs may contribute to
host defense toward bacterial insults.},
url = {http://iai.asm.org/cgi/content/abstract/78/2/854}
}
@ARTICLE{Ronsyn2007,
author = {Ronsyn, Mark and Daans, Jasmijn and Spaepen, Gie and Chatterjee,
Shyama and Vermeulen, Katrien and D'Haese, Patrick and Van Tendeloo,
Viggo and Van Marck, Eric and Ysebaert, Dirk and Berneman, Zwi and
Jorens, Philippe and Ponsaerts, Peter},
title = {Plasmid-based genetic modification of human bone marrow-derived stromal
cells: analysis of cell survival and transgene expression after transplantation
in rat spinal cord},
journal = {BMC Biotechnology},
year = {2007},
volume = {7},
pages = {90},
number = {1},
abstract = {BACKGROUND:Bone marrow-derived stromal cells (MSC) are attractive
targets for ex vivo cell and gene therapy. In this context, we investigated
the feasibility of a plasmid-based strategy for genetic modification
of human (h)MSC with enhanced green fluorescent protein (EGFP) and
neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP,
NT3, NT3-EGFP) were established and used to study cell survival and
transgene expression following transplantation in rat spinal cord.RESULTS:First,
we demonstrate long-term survival of transplanted hMSC-EGFP cells
in rat spinal cord under, but not without, appropriate immune suppression.
Next, we examined the stability of EGFP or NT3 transgene expression
following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP
in rat spinal cord. While in vivo EGFP mRNA and protein expression
by transplanted hMSC-EGFP cells was readily detectable at different
time points post-transplantation, in vivo NT3 mRNA expression by
hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP
cells was, respectively, undetectable or declined rapidly between
day 1 and 7 post-transplantation. Further investigation revealed
that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP
cells: (i) was associated with a decrease in transgenic NT3-EGFP
mRNA expression as suggested following laser capture micro-dissection
analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation,
(ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously,
and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell
cultures at 2 weeks post-transplantation. Finally, because we observed
a slowly progressing tumour growth following transplantation of all
our hMSC cell transplants, we here demonstrate that omitting immune
suppressive therapy is sufficient to prevent further tumour growth
and to eradicate malignant xenogeneic cell transplants.CONCLUSION:In
this study, we demonstrate that genetically modified hMSC lines can
survive in healthy rat spinal cord over at least 3 weeks by using
adequate immune suppression and can serve as vehicles for transgene
expression. However, before genetically modified hMSC can potentially
be used in a clinical setting to treat spinal cord injuries, more
research on standardisation of hMSC culture and genetic modification
needs to be done in order to prevent tumour formation and transgene
silencing in vivo.},
doi = {10.1186/1472-6750-7-90},
issn = {1472-6750},
owner = {Meike Kuschel},
pubmedid = {18078525},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1472-6750/7/90}
}
@ARTICLE{Rooman2006,
author = {Rooman, Ilse and De Medts, Nele and Baeyens, Luc and Lardon, Jessy
and De Breuck, Saskia and Heimberg, Harry and Bouwens, Luc},
title = {Expression of the Notch Signaling Pathway and Effect on Exocrine
Cell Proliferation in Adult Rat Pancreas},
journal = {Am. J. Pathol.},
year = {2006},
volume = {169},
pages = {1206--1214},
number = {4},
month = oct,
abstract = {When pancreatic tissue is injured after duct obstruction, acinoductal
metaplasia is observed. Similar metaplastic changes occur when exocrine
pancreatic cells are isolated and cultured. We demonstrate that under
these experimental conditions the exocrine acinar cells lose their
differentiated characteristics: expression of the acinar transcription
factors p48/Ptf1{alpha} and Mist1 is decreased or lost, whereas expression
of the embryonic transcription factor Pdx1 is increased. The receptors
Notch1 and Notch2, members of the DSL family of Notch ligands, and
the target genes in the Notch-signaling pathway Hes1, Hey1, and Hey2
become strongly up-regulated. We noted also reduced expression of
Sel1L, a Notch repressor that is normally highly expressed in exocrine
pancreas. Stimulation of Notch by its ligand Jagged1 diminished the
proliferation of cultured metaplastic exocrine cells. Chemical inhibition
of Notch signaling resulted in increased proliferation and induction
of the cell-cycle regulator p21Cip1. This effect seems to be Hes1-independent
and mainly coincides with decreased Hey1 and Hey2 mRNA expression.
In conclusion, we demonstrate that during acinoductal metaplasia
the Notch-signaling pathway is activated concomitantly with changes
in transcription factor expression of pancreatic acinar cells. In
addition, we show that Notch signaling is implicated in the suppression
of proliferation of these metaplastic exocrine cells. The latter
may be important in protection from neoplastic transformation.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/169/4/1206}
}
@ARTICLE{Roon2010,
author = {van Roon, Eddy and van Puijenbroek, Marjo and Middeldorp, Anneke
and van Eijk, Ronald and de Meijer, Emile and Erasmus, Dianhdra and
Wouters, Kim and van Engeland, Manon and Oosting, Jan and Hes, Frederik
and Tops, Carli and van Wezel, Tom and Boer, Judith and Morreau,
Hans},
title = {Early onset MSI-H colon cancer with MLH1 promoter methylation, is
there a genetic predisposition?},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {180},
number = {1},
abstract = {BACKGROUND:To investigate the etiology of MLH1 promoter methylation
in mismatch repair (MMR) mutation-negative early onset MSI-H colon
cancer. As this type of colon cancer is associated with high ages,
young patients bearing this type of malignancy are rare and could
provide additional insight into the etiology of sporadic MSI-H colon
cancer.METHODS:We studied a set of 46 MSI-H colon tumors cases with
MLH1 promoter methylation which was enriched for patients with an
age of onset below 50 years (n = 13). Tumors were tested for CIMP
marker methylation and mutations linked to methylation: BRAF, KRAS,
GADD45A and the MLH1 -93G>A polymorphism. When available, normal
colon and leukocyte DNA was tested for GADD45A mutations and germline
MLH1 methylation. SNP array analysis was performed on a subset of
tumors.RESULTS:We identified two cases (33 and 60 years) with MLH1
germline promoter methylation. BRAF mutations were less frequent
in colon cancer patients below 50 years relative to patients above
50 years (p-value: 0.044). CIMP-high was infrequent and related to
BRAF mutations in patients below 50 years. In comparison with published
controls the G>A polymorphism was associated with our cohort. Although
similar distribution of the pathogenic A allele was observed in the
patients with an age of onset above and below 50 years, the significance
for the association was lost for the group under 50 years. GADD45A
sequencing yielded an unclassified variant. Tumors from both age
groups showed infrequent copy number changes and loss-of-heterozygosity.CONCLUSION:Somatic
or germline GADD45A mutations did not explain sporadic MSI-H colon
cancer. Although germline MLH1 methylation was found in two individuals,
locus-specific somatic MLH1 hypermethylation explained the majority
of sporadic early onset MSI-H colon cancer cases. Our data do not
suggest an intrinsic tendency for CpG island hypermethylation in
these early onset MSI-H tumors other than through somatic mutation
of BRAF.},
doi = {10.1186/1471-2407-10-180},
issn = {1471-2407},
pubmedid = {20444249},
url = {http://www.biomedcentral.com/1471-2407/10/180}
}
@ARTICLE{Rooney2011,
author = {Rooney, Brian and O'Donovan, Helen and Gaffney, Andrew and Browne,
Marie and Faherty, Noel and Curran, Simon P. and Sadlier, Denise
and Godson, Catherine and Brazil, Derek P. and Crean, John},
title = {CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through
LRP6: Implications for the pathogenesis of diabetic nephropathy},
journal = {FEBS Letters},
year = {2011},
volume = {585},
pages = {531--538},
number = {3},
month = feb,
abstract = {We describe the activation of Wnt signalling in mesangial cells by
CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3[beta] resulting
in accumulation and nuclear localisation of [beta]-catenin, TCF/LEF
activity and expression of Wnt targets. This is coincident with decreased
phosphorylation of [beta]-catenin on Ser 33/37 and increased phosphorylation
on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2's effects. Microarray
analyses of diabetic patients identified differentially expressed
Wnt components. [beta]-Catenin is increased in type 1 diabetic and
UUO mice and in in vitro models of hyperglycaemia and hypertension.
These findings suggest that Wnt/CCN2 signalling plays a role in the
pathogenesis of diabetic nephropathy.},
issn = {0014-5793},
keywords = {Connective tissue growth factor, Wnt, Glycogen synthase kinase 3[beta],
[beta]-Catenin, LRP6, Diabetic nephropathy},
url = {http://www.sciencedirect.com/science/article/pii/S001457931100024X}
}
@ARTICLE{Roosa2011,
author = {Sara M. Mantila Roosa and Yunlong Liu and Charles H. Turner},
title = {Alternative splicing in bone following mechanical loading},
journal = {Bone},
year = {2011},
volume = {48},
pages = {543 - 551},
number = {3},
abstract = {It is estimated that more than 90% of human genes express multiple
mRNA transcripts due to alternative splicing. Consequently, the proteins
produced by different splice variants will likely have different
functions and expression levels. Several genes with splice variants
are known in bone, with functions that affect osteoblast function
and bone formation. The primary goal of this study was to evaluate
the extent of alternative splicing in a bone subjected to mechanical
loading and subsequent bone formation. We used the rat forelimb loading
model, in which the right forelimb was loaded axially for 3 min,
while the left forearm served as a non-loaded control. Animals were
subjected to loading sessions every day, with 24 h between sessions.
Ulnae were sampled at 11 time points, from 4 h to 32 days after
beginning loading. RNA was isolated and mRNA abundance was measured
at each time point using Affymetrix exon arrays (GeneChip® Rat Exon
1.0 ST Arrays). An ANOVA model was used to identify potential alternatively
spliced genes across the time course, and five alternatively spliced
genes were validated with qPCR: Akap12, Fn1, Pcolce, Sfrp4, and Tpm1.
The number of alternatively spliced genes varied with time, ranging
from a low of 68 at 12 h to a high of 992 at 16d. We identified
genes across the time course that encoded proteins with known functions
in bone formation, including collagens, matrix proteins, and components
of the Wnt/β-catenin and TGF-β signaling pathways. We also identified
alternatively spliced genes encoding cytokines, ion channels, muscle-related
genes, and solute carriers that do not have a known function in bone
formation and represent potentially novel findings. In addition,
a functional characterization was performed to categorize the global
functions of the alternatively spliced genes in our data set. In
conclusion, mechanical loading induces alternative splicing in bone,
which may play an important role in the response of bone to mechanical
loading.},
doi = {10.1016/j.bone.2010.11.006},
issn = {8756-3282},
keywords = {Alternative splicing},
url = {http://www.sciencedirect.com/science/article/pii/S8756328210020375}
}
@ARTICLE{Rope2011,
author = {Alan F. Rope and Kai Wang and Rune Evjenth and Jinchuan Xing and
Jennifer J. Johnston and Jeffrey J. Swensen and W. Evan Johnson
and Barry Moore and Chad D. Huff and Lynne M. Bird and John C.
Carey and John M. Opitz and Cathy A. Stevens and Tao Jiang and
Christa Schank and Heidi Deborah Fain and Reid Robison and Brian
Dalley and Steven Chin and Sarah T. South and Theodore J. Pysher
and Lynn B. Jorde and Hakon Hakonarson and Johan R. Lillehaug and
Leslie G. Biesecker and Mark Yandell and Thomas Arnesen and Gholson J.
Lyon},
title = {Using VAAST to Identify an X-Linked Disorder Resulting in Lethality
in Male Infants Due to N-Terminal Acetyltransferase Deficiency},
journal = {The American Journal of Human Genetics},
year = {2011},
volume = {89},
pages = {28 - 43},
number = {1},
abstract = {We have identified two families with a previously undescribed lethal
X-linked disorder of infancy; the disorder comprises a distinct combination
of an aged appearance, craniofacial anomalies, hypotonia, global
developmental delays, cryptorchidism, and cardiac arrhythmias. Using
X chromosome exon sequencing and a recently developed probabilistic
algorithm aimed at discovering disease-causing variants, we identified
in one family a c.109T>C (p.Ser37Pro) variant in NAA10, a gene
encoding the catalytic subunit of the major human N-terminal acetyltransferase
(NAT). A parallel effort on a second unrelated family converged on
the same variant. The absence of this variant in controls, the amino
acid conservation of this region of the protein, the predicted disruptive
change, and the co-occurrence in two unrelated families with the
same rare disorder suggest that this is the pathogenic mutation.
We confirmed this by demonstrating a significantly impaired biochemical
activity of the mutant hNaa10p, and from this we conclude that a
reduction in acetylation by hNaa10p causes this disease. Here we
provide evidence of a human genetic disorder resulting from direct
impairment of N-terminal acetylation, one of the most common protein
modifications in humans.},
doi = {10.1016/j.ajhg.2011.05.017},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S0002929711002102}
}
@ARTICLE{Roper2006,
author = {Roper, Michael G. and Frisk, Megan L. and Oberlander, Janeen P. and
Ferrance, Jerome P. and McGrory, Brian J. and Landers, James P.},
title = {Extraction of C-reactive protein from serum on a microfluidic chip},
journal = {Analytica Chimica Acta},
year = {2006},
volume = {569},
pages = {195--202},
number = {1-2},
month = may,
abstract = {The first extraction of a protein, C-reactive protein (CRP), from
unadulterated serum on a microfluidic chip is demonstrated. Two stationary
phases were evaluated for their ability to selectively extract this
protein directly from serum without the need for additional cleanup
steps. The first extraction media tested was an affinity matrix containing
monoclonal antibodies to CRP, however, after immobilization this
media failed to bind CRP. The more efficient stationary phase, immobilized
phosphocholine, extracted CRP in a Ca2+-dependent manner. Significant
non-specific binding by more abundant serum proteins was observed
using typical washing protocols with this phase and these protocols
were modified and optimized to yield extractions that were selective
to phosphocholine-binding proteins. Extraction efficiencies were
40% for standard CRP solutions and run-to-run extraction reproducibility
was 15% for 8 [mu]L of total serum loaded. Serum concentrations of
CRP determined by this method in patients who had undergone hip replacement
surgery compared favorably with those values obtained by the conventional,
currently utilized methods. Thus, this newly developed miniaturized
method for protein purification from serum will provide a foundation
for future extractions of protein biomarkers.},
issn = {0003-2670},
keywords = {Microchip, Serum, Extraction, Proteins},
url = {http://www.sciencedirect.com/science/article/B6TF4-4JMV291-3/2/cb4eee92c47fe7f89b9f52e23cf6efd4}
}
@ARTICLE{Roppolo2006,
author = {Roppolo, Daniele and Ribaud, Virginie and Jungo, Véronique Pauli
and Lüscher, Christian and Rodriguez, Ivan},
title = {Projection of the Grüneberg ganglion to the mouse olfactory bulb},
journal = {European Journal of Neuroscience},
year = {2006},
volume = {23},
pages = {2887--2894},
number = {11},
abstract = {Abstract In mammals, sensory neurons from the main olfactory and vomeronasal
systems project their axons to the olfactory bulbs in the brain.
We here report that a cluster of neurons, distinct from these two
systems, located at the very tip of the mouse nose and called the
Grüneberg ganglion expresses the mature olfactory-sensory neuron-specific
marker olfactory marker protein (OMP), but is unlikely to express
known odorant or pheromone receptors. The ganglion is present at
birth and maintained during adult life. Tracing experiments indicate
that these neurons target ipsilaterally to a specific set of glomeruli
located on the caudal part of the olfactory bulb, and that this connection
is necessary for the survival of the ganglion. The glomerular targets
are structures previously proposed to be associated with suckling
behaviour. These observations strongly suggest that this peculiar
olfactory neuronal population plays a sensory role, possibly linked
to chemoperception.},
issn = {1460-9568},
keywords = {axonal projections, Grueneberg ganglion, olfactory system, sensory
systems},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2006.04818.x}
}
@ARTICLE{Ros2006,
author = {Ros, Alexandra and Hellmich, Wibke and Regtmeier, Jan and Duong,
Thanh Tu and Anselmetti, Dario},
title = {Bioanalysis in structured microfluidic systems},
journal = {ELECTROPHORESIS},
year = {2006},
volume = {27},
pages = {2651--2658},
number = {13},
abstract = {Abstract Microfluidic and lab-on-a-chip devices have attracted widespread
interest in separation sciences and bioanalysis. Recent designs in
microfluidic devices extend common separation concepts by exploiting
new phenomena for molecular dynamics on a length scale of 10 μm
and below, giving rise to novel manipulation tools and nonintuitive
phenomena for microseparations. Here, we focus on three very recent
developments for bioseparations based on tailored microfluidic systems:
Single cell navigation, trapping and steering with subsequent on-chip
lysis, protein separation and LIF detection (Section 3.1), then we
report dielectrophoretic trapping and separation of large DNA fragments
in structured microfluidic devices (Section 3.2). Finally, a paradoxial
migration phenomenon based on thermal fluctuations, periodically
arranged microchannels and a biased alternating current electric
field is presented in Section 3.3.},
issn = {1522-2683},
keywords = {DNA, Microfluidic device, Migration phenomena, Protein, Single cell
analytics},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200500923}
}
@ARTICLE{Rosa2009,
author = {Rosa, Ilaria Dalla and Goffart, Steffi and Wurm, Melanie and Wiek,
Constanze and Essmann, Frank and Sobek, Stefan and Schroeder, Peter
and Zhang, Hongliang and Krutmann, Jean and Hanenberg, Helmut and
Schulze-Osthoff, Klaus and Mielke, Christian and Pommier, Yves and
Boege, Fritz and Christensen, Morten O.},
title = {Adaptation of topoisomerase I paralogs to nuclear and mitochondrial
DNA},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {6414--6428},
number = {19},
month = oct,
abstract = {Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria.
In yeast, a single topoisomerase I gene provides for both organelles.
In vertebrates, topoisomerase I is divided into nuclear and mitochondrial
paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication,
we targeted Top1 to mitochondria or Top1mt to nuclei. Overexpression
in the fitting organelle served as control. Targeting of Top1 to
mitochondria blocked transcription and depleted mitochondrial DNA.
This was also seen with catalytically inactive Top1 mutants, but
not with Top1mt overexpressed in mitochondria. Targeting of Top1mt
to the nucleus revealed that it was much less able to interact with
mitotic chromosomes than Top1 overexpressed in the nucleus. Similar
experiments with Top1/Top1mt hybrids assigned these functional differences
to structural divergences in the DNA-binding core domains. We propose
that adaptation of this domain to different chromatin environments
in nuclei and mitochondria has driven evolutional development and
conservation of organelle-restricted topoisomerase I paralogs in
vertebrates.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/19/6414}
}
@ARTICLE{Roscoe2009,
author = {Roscoe, W.A. and Welsh, M.E. and Carter, D.E. and Karlik, S.J.},
title = {VEGF and angiogenesis in acute and chronic MOG(35-55) peptide induced
EAE},
journal = {Journal of Neuroimmunology},
year = {2009},
volume = {209},
pages = {6--15},
number = {1-2},
month = apr,
abstract = {An increased expression of vascular endothelial growth factor (VEGF)
is associated with demyelinated lesions in both multiple sclerosis
(MS) and its model (EAE), implicating changes in vasculature as a
potential component of CNS plaque formation. The purpose of this
study was to investigate the vascular changes in acute and chronic
EAE in C57BL/6 mice induced with myelin oligodendrocyte glycoprotein
(MOG 35-55) peptide. We investigated the functional contribution
of VEGF to acute and chronic EAE by treating immunized mice with
SU5416 (Semaxinib), a potent and selective inhibitor of VEGF receptor
2 (VEGFR2). Animals received seven daily injections of SU5416 (50 mg/kg)
or vehicle beginning on the day after disease onset (acute study)
or on day 45 post-immunization (chronic study). Spinal cord sections
were collected on the day of sacrifice. Modulation of angiogenic
gene expression was determined using RNA isolated from 4 acute and
4 non-immunized controls. MOG peptide induction produced extensive
demyelination, immune cell infiltration, tissue laminin deposits,
and axonal loss in lesions. VEGF expression was extensively increased
in the acute mice, which correlated positively with clinical score.
In the acute study, SU5416 treatment produced a significant clinical
improvement versus vehicle controls (p < 0.001), with less demyelination
(- 37%) and cellular infiltration (- 23%) in the spinal cord (p < 0.05).
Treated animals also had significantly fewer blood vessels per section
than controls (56.1 ± 6.1 v. 81.6 ± 11.5, p < 0.05), and significantly
reduced laminin abnormalities (28.9% of lesion area v. 46.8%, p < 0.05).
There was no improvement in clinical score or tissue pathology, and
no difference in vessel number or lesion laminin expression, when
SU5416 was administered during the chronic disease (all p > 0.05).
In the acute study only, VEGF staining correlated with demyelination
and the extent of cellular infiltration in both control (r = 0.723,
r = 0.665) and treated (r = 0.681, r = 0.487) animals (all p < 0.05).
Laminin staining in lesion areas was strongly correlated with tissue
pathology for all animals in both the acute and chronic study (all
p < 0.001). Vascular alterations in MOG peptide-induced EAE in the
mouse are accompanied by increased lesion-specific levels of VEGF,
extensive laminin deposits in the tissue and altered transcription
of numerous angiogenic factors. In the microarray studies, acute
mice showed a significant increase in several angiogenic RNA transcripts,
six of which were verified by RT-PCR, alanyl aminopeptidase, caspase
8, Hif1a, MMP-19, plasminogen activator inhibitor, and thrombospondin1.},
issn = {0165-5728},
keywords = {EAE, Multiple sclerosis, MS, Angiogenesis, VEGF, Remyelination, Alanyl
aminopeptidase, Plasminogen activator inhibitor, Caspase 8, Thrombospondin,
Hif1a, MMP-19, Laminin, SU5416},
url = {http://www.sciencedirect.com/science/article/B6T03-4VP12C3-1/2/264baffefeb3b04c37dfbecce91b9d25}
}
@ARTICLE{Rose2008,
author = {Rose, Patricia and Bond, Jeffrey and Tighe, Scott and Toth, Michael
J. and Wellman, Theresa L. and de Montiano, Eva Maria Briso and Lewinter,
Martin M. and Lounsbury, Karen M.},
title = {Genes overexpressed in cerebral arteries following salt-induced hypertensive
disease are regulated by angiotensin II, JunB, and CREB},
journal = {Am J Physiol Heart Circ Physiol},
year = {2008},
volume = {294},
pages = {H1075--1085},
number = {2},
month = feb,
abstract = {Although changes in gene expression are necessary for arterial remodeling
during hypertension, the genes altered and their mechanisms of regulation
remain uncertain. The goal of this study was to identify cerebral
artery genes altered by hypertension and define signaling pathways
important in their regulation. Intact cerebral arteries from Dahl
salt-sensitive normotensive and hypertensive high-salt (HS) rats
were examined by immunostaining, revealing an increased phosphorylation
of extracellular signal-regulated kinase 1/2 (ERK1/2) and expression
of the proliferative marker Ki-67 in arteries from hypertensive animals.
Arterial RNA analyzed by microarray and validated with RT-quantitative
PCR revealed that jun family member junB and matricellular genes
plasminogen activator inhibitor-1 (PAI-1) and osteopontin (OPN) were
significantly overexpressed in HS arteries. Fisher exact test and
annotation-based gene subsets showed that genes upregulated by Jun
and Ca2+/cAMP-response element-binding protein (CREB) were overrepresented.
A model of cultured rat cerebrovascular smooth muscle cells was used
to test the hypothesis that angiotensin II (ANG II), JunB, and CREB
are important in the regulation of genes identified in the rat hypertension
model. ANG II induced a transient induction of junB and a delayed
induction of PAI-1 and OPN mRNA levels, which were reduced by ERK
inhibition with U-0126. Silencing junB using small-interfering RNA
reduced mRNA levels of OPN but not PAI-1. The silencing of CREB reduced
PAI-1 induction by ANG II but enhanced the transcription of OPN.
Together, these results suggest that salt-induced hypertensive disease
promotes changes in matricellular genes that are stimulated by ANG
II, regulated by ERK, and selectively regulated by JunB and CREB.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/294/2/H1075}
}
@ARTICLE{Rose2007,
author = {Rose, R. Wesley and Vorobyeva, Anna G. and Skipworth, Jason D. and
Nicolas, Emmanuelle and Rall, Glenn F.},
title = {Altered levels of STAT1 and STAT3 influence the neuronal response
to interferon gamma},
journal = {Journal of Neuroimmunology},
year = {2007},
volume = {192},
pages = {145--156},
number = {1-2},
month = dec,
abstract = {As immune responses in the CNS are highly regulated, cell-specific
differences in IFN[gamma] signaling may be integral in dictating
the outcome of host cell responses. In comparing the response of
IFN[gamma]-treated primary neurons to control MEF, we observed that
neurons demonstrated lower basal expression of both STAT1 and STAT3,
the primary signal transducers responsible for IFN[gamma] signaling.
Following IFN[gamma] treatment of these cell populations, we noted
muted and delayed STAT1 phosphorylation, no detectable STAT3 phosphorylation,
and a 3-10-fold lower level of representative IFN[gamma]-responsive
gene transcripts. Moreover, in response to a brief pulse of IFN[gamma],
a steady increase in STAT1 phosphorylation and IFN[gamma] gene expression
over 48 h was observed in neurons, as compared to rapid attenuation
in MEF. These distinct response kinetics in IFN[gamma]-stimulated
neurons may reflect modifications in the IFN[gamma] negative feedback
loop, which may provide a mechanism for the cell-specific heterogeneity
of responses to IFN[gamma].},
issn = {0165-5728},
keywords = {Cytokine, Signal transduction, Gene regulation, Neuron, Interferon
gamma, STAT1, STAT3},
url = {http://www.sciencedirect.com/science/article/B6T03-4R5G334-3/2/cc7e3da8bae1b76e99df1f354fa30fa1}
}
@ARTICLE{Rose2005,
author = {Rose, Scott D. and Kim, Dong-Ho and Amarzguioui, Mohammed and Heidel,
Jeremy D. and Collingwood, Michael A. and Davis, Mark E. and Rossi,
John J. and Behlke, Mark A.},
title = {Functional polarity is introduced by Dicer processing of short substrate
RNAs},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {4140--4156},
number = {13},
month = jul,
abstract = {Synthetic RNA duplexes that are substrates for Dicer are potent triggers
of RNA interference (RNAi). Blunt 27mer duplexes can be up to 100-fold
more potent than traditional 21mer duplexes (1). Not all 27mer duplexes
show increased potency. Evaluation of the products of in vitro dicing
reactions using electrospray ionization mass spectrometry reveals
that a variety of products can be produced by Dicer cleavage. Use
of asymmetric duplexes having a single 2-base 3'-overhang restricts
the heterogeneity that results from dicing. Inclusion of DNA residues
at the ends of blunt duplexes also limits heterogeneity. Combination
of asymmetric 2-base 3'-overhang with 3'-DNA residues on the blunt
end result in a duplex form which directs dicing to predictably yield
a single primary cleavage product. It is therefore possible to design
a 27mer duplex which is processed by Dicer to yield a specific, desired
21mer species. Using this strategy, two different 27mers can be designed
that result in the same 21mer after dicing, one where the 3'-overhang
resides on the antisense (AS) strand and dicing proceeds to the right'
( R') and one where the 3'-overhang resides on the sense (S) strand
and dicing proceeds to the left' ( L'). Interestingly, the R' version
of the asymmetric 27mer is generally more potent in reducing target
gene levels than the L' version 27mer. Strand targeting experiments
show asymmetric strand utilization between the two different 27mer
forms, with the R' form favoring S strand and the L' form favoring
AS strand silencing. Thus, Dicer processing confers functional polarity
within the RNAi pathway.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/13/4140}
}
@ARTICLE{Rosello-Lleti2012,
author = {Esther Roselló-Lletí and Miguel Rivera and Raquel Cortéss and Inmaculada
Azorín and Rafael Sirera and Luis Martínez-Dolz and Leif Hove and
Juan Cinca and Francisca Lago and José R. González-Juanatey and Antonio
Salvador and Manuel Portolés},
title = {Influence of Heart Failure on Nucleolar Organization and Protein
Expression in Human Hearts},
journal = {Biochemical and Biophysical Research Communications},
year = {2012},
volume = {na},
pages = { - },
number = {0},
abstract = {We investigate for the first time the influence of heart failure (HF)
on nucleolar organization and proteins in patients with ischemic
(ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts
from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation
and control donors (n=6), were analysed by western-blotting, RT-PCR
and cell biology methods. When we compared protein levels according
to HF etiology, nucleolin was increased in both ICM (117%, p<0.05)
and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated
in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence
studies showed that the highest intensity of nucleolin was into nucleolus
(p<0.0001), and it was increased in pathological hearts (p<0.0001).
Ultrastructure analysis by electron microscopy showed an increase
in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%,
p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar
organization was influenced by HF irrespective of etiology, increasing
fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01)
and dense fibrillar components (p<0.01). Finally, left ventricular
function parameters were related with nucleolin levels in ischemic
hearts (p<0.0001). The present study demonstrates that HF influences
on morphology and organization of nucleolar components, revealing
changes in the expression and in the levels of nucleolin protein.},
doi = {10.1016/j.bbrc.2011.12.151},
issn = {0006-291X},
keywords = {Nucleolus},
url = {http://www.sciencedirect.com/science/article/pii/S0006291X12000046?v=s5}
}
@ARTICLE{Rosen2004,
author = {Rosen, Clifford J. and Ackert-Bicknell, Cheryl L. and Adamo, Martin
L. and Shultz, Kathy L. and Rubin, Janet and Donahue, Leah Rae and
Horton, Lindsay G. and Delahunty, Krista M. and Beamer, Wesley G.
and Sipos, Jennifer and Clemmons, David and Nelson, Tracy and Bouxsein,
Mary L. and Horowitz, Mark},
title = {Congenic mice with low serum IGF-I have increased body fat, reduced
bone mineral density, and an altered osteoblast differentiation program},
journal = {Bone},
year = {2004},
volume = {35},
pages = {1046--1058},
number = {5},
month = nov,
abstract = {Targeted gene studies have demonstrated the importance of insulin-like
growth factor-I (IGF-I) for osteoblast (OB) differentiation and the
acquisition of peak bone mineral density (BMD). The skeletal response
to allelic differences in IGF-I expression can also be measured in
vivo, using congenic mice. We created a congenic strain with reduced
(approximately 20%) circulating IGF-I (C3H.B6-6T [6T]) by backcrossing
a small genomic region (30 cM) of Chromosome 6 (Chr6) from C3H/HeJ
(C3H) onto a C57Bl/6J (B6) background. 6T female mice have lower
serum IGF-I (P < 0.001 vs. B6) but similar growth hormone (GH) and
serum IGF binding protein (IGFBP) concentrations as B6. At 16 weeks
of age, congenics have greater body fat (P < 0.02 vs. B6) despite
less total body weight, and exhibit smaller femoral cross-sectional
size (P = 0.001), reduced cortical thickness (P < 0.001) and lower
trabecular BV/TV (P < 0.05) than B6. 6T mice also have suppressed
serum leptin (P < 0.01), but compared to B6 have similar markers
of bone resorption (i.e., urine CTx and serum TRAP 5B). At 8 weeks
of age, skeletal IGF-I mRNA from long bones was reduced by 40% (P
< 0.05) as were liver mRNA transcripts (i.e., 50%, P < 0.01). Osteoblast
progenitors from the bone marrow of 6T mice formed less colony forming
unit fibroblasts by crystal violet staining than B6 (P < 0.007) and
had significantly reduced alkaline phosphatase-positive colonies
than B6(P < 0.0001). In addition, staining of bone marrow with oil
red O revealed greater numbers of adipocytes in 6T than B6. Several
candidate genes in the Chr6 QTL were excluded by lack of strain-related
expression differences in bone, but genes positively regulating adipocyte
differentiation including Alox 5 and PPAR-[gamma] require further
study as either "pathway" or candidate genes. In summary, allelic
differences in a QTL on Chr6 result in altered IGF-I gene expression,
changes in OB lineage allocation, and reduced peak bone mass. Congenic
mice are useful models not only for mapping genes related to bone
mass but also for elucidating the biology underlying various skeletal
phenotypes associated with more subtle manipulation of the mouse
genome.},
issn = {8756-3282},
keywords = {Serum, Osteoblast, Adipocyte},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4DCN0MM-6/2/ca7850ebf00fc95257c01b9ea3dae2d9}
}
@ARTICLE{Rosen2005,
author = {Rosen, Jennifer and He, Mei and Umbricht, Christopher and Alexander,
H. Richard and Dackiw, Alan P.B. and Zeiger, Martha A. and Libutti,
Steven K.},
title = {A six-gene model for differentiating benign from malignant thyroid
tumors on the basis of gene expression},
journal = {Surgery},
year = {2005},
volume = {138},
pages = {1050--1057},
number = {6},
month = dec,
abstract = {Background Thyroid nodules are common; fine-needle aspirations commonly
are read as indeterminate, necessitating surgery to exclude carcinoma.
We developed a 6-gene array-based predictor model to diagnose benign
versus malignant thyroid lesions. In this study, we verified whether
quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
using this model reliably can differentiate benign from malignant
thyroid nodules.Methods Molecular profiles of benign (follicular
adenomas, hyperplastic nodules) and malignant tumors (papillary thyroid
carcinomas, follicular variants of papillary thyroid carcinomas)
were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031,
Hs.24183, LSM7, SYNGR2, C21orf4). The gold standard was standard
pathologic criteria. A diagnosis-predictor model was built by using
the training samples and was then used to predict the class of 10
additional samples analyzed as unknowns.Results Our predictor model
using 47 training samples correctly predicted 9/10 unknowns. One
sample diagnosed as benign by standard histologic criteria was diagnosed
as malignant by our model (sensitivity 75%; specificity, 100%; positive
predictive value, 100%; negative predictive value, 85.7%).Conclusions
Molecular diagnosis with our 6-gene model can differentiate between
benign and malignant thyroid tumors with high sensitivity and specificity.
In combination, these genetic markers may be a reliable test to preoperatively
diagnose the malignant potential of thyroid nodules.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4HTKSJG-M/2/252210b762d585cecc99ef67094dacf6}
}
@ARTICLE{Rosen2008,
author = {Rosen, Mitchell B. and Abbott, Barbara D. and Wolf, Douglas C. and
Corton, J. Christopher and Wood, Carmen R. and Schmid, Judith E.
and Das, Kaberi P. and Zehr, Robert D. and Blair, Eric T. and Lau,
Christopher},
title = {Gene Profiling in the Livers of Wild-type and PPAR{alpha}-Null Mice
Exposed to Perfluorooctanoic Acid},
journal = {Toxicol Pathol},
year = {2008},
volume = {36},
pages = {592--607},
number = {4},
month = jun,
abstract = {Health concerns have been raised because perfluorooctanoic acid (PFOA)
is commonly found in the environment and can be detected in humans.
In rodents, PFOA is a carcinogen and a developmental toxicant. PFOA
is a peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})
activator; however, PFOA is capable of inducing heptomegaly in the
PPAR{alpha}-null mouse. To study the mechanism associated with PFOA
toxicity, wild-type and PPAR{alpha}-null mice were orally dosed for
7 days with PFOA (1 or 3 mg/kg) or the PPAR{alpha} agonist Wy14,643
(50 mg/kg). Gene expression was evaluated using commercial microarrays.
In wild-type mice, PFOA and Wy14,643 induced changes consistent with
activation of PPAR{alpha}. PFOA-treated wild-type mice deviated from
Wy14,643-exposed mice with respect to genes involved in xenobiotic
metabolism. In PFOA-treated null mice, changes were observed in transcripts
related to fatty acid metabolism, inflammation, xenobiotic metabolism,
and cell cycle regulation. Hence, a component of the PFOA response
was found to be independent of PPAR{alpha}. Although the signaling
pathways responsible for these effects are not readily apparent,
overlapping gene regulation by additional PPAR isoforms could account
for changes related to fatty acid metabolism and inflammation, whereas
regulation of xenobiotic metabolizing genes is suggestive of constitutive
androstane receptor activation.},
url = {http://tpx.sagepub.com/cgi/content/abstract/36/4/592}
}
@ARTICLE{Rosen2008a,
author = {Rosen, Mitchell B. and Lee, Janice S. and Ren, Hongzu and Vallanat,
Beena and Liu, Jie and Waalkes, Michael P. and Abbott, Barbara D.
and Lau, Christopher and Corton, J. Christopher},
title = {Toxicogenomic Dissection of the Perfluorooctanoic Acid Transcript
Profile in Mouse Liver: Evidence for the Involvement of Nuclear Receptors
PPAR{alpha} and CAR},
journal = {Toxicol. Sci.},
year = {2008},
volume = {103},
pages = {46--56},
number = {1},
month = may,
abstract = {A number of perfluorinated alkyl acids including perfluorooctanoic
acid (PFOA) elicit effects similar to peroxisome proliferator chemicals
(PPC) in mouse and rat liver. There is strong evidence that PPC cause
many of their effects linked to liver cancer through the nuclear
receptor peroxisome proliferator-activated receptor alpha (PPAR{alpha}).
To determine the role of PPAR{alpha} in mediating PFOA transcriptional
events, we compared the transcript profiles of the livers of wild-type
or PPAR{alpha}-null mice exposed to PFOA or the PPAR{alpha} agonist
WY-14,643 (WY). After 7 days of exposure, 85% or 99.7% of the genes
altered by PFOA or WY exposure, respectively were dependent on PPAR{alpha}.
The PPAR{alpha}-independent genes regulated by PFOA included those
involved in lipid homeostasis and xenobiotic metabolism. Many of
the lipid homeostasis genes including acyl-CoA oxidase (Acox1) were
also regulated by WY in a PPAR{alpha}-dependent manner. The increased
expression of these genes in PPAR{alpha}-null mice may be partly
due to increases in PPAR{gamma} expression upon PFOA exposure. Many
of the identified xenobiotic metabolism genes are known to be under
control of the nuclear receptor CAR (constitutive activated/androstane
receptor) and the transcription factor Nrf2 (nuclear factor erythroid
2-related factor 2). There was excellent correlation between the
transcript profile of PPAR{alpha}-independent PFOA genes and those
of activators of CAR including phenobarbital and 1,4-bis[2-(3,5-dichloropyridyloxy)]
benzene (TCPOBOP) but not those regulated by the Nrf2 activator,
dithiol-3-thione. These results indicate that PFOA alters most genes
in wild-type mouse liver through PPAR{alpha}, but that a subset of
genes are regulated by CAR and possibly PPAR{gamma} in the PPAR{alpha}-null
mouse.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/103/1/46}
}
@ARTICLE{Rosen2009,
author = {Rosen, Mitchell B. and Schmid, Judith E. and Das, Kaberi P. and Wood,
Carmen R. and Zehr, Robert D. and Lau, Christopher},
title = {Gene expression profiling in the liver and lung of perfluorooctane
sulfonate-exposed mouse fetuses: Comparison to changes induced by
exposure to perfluorooctanoic acid},
journal = {Reproductive Toxicology},
year = {2009},
volume = {27},
pages = {278--288},
number = {3-4},
month = jun,
abstract = {Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)
are environmental contaminants found in the tissues of humans and
wildlife. They are activators of peroxisome proliferator-activated
receptor-alpha (PPAR[alpha]) and exhibit hepatocarcinogenic potential
in rats. PFOS and PFOA are also developmental toxicants in rodents
and PFOS has been shown to induce pulmonary deficits in rat offspring.
Pregnant CD-1 mice were dosed with 0, 5, or 10 mg/kg PFOS from gestation
days 1-17. Transcript profiling was conducted on the fetal liver
and lung. Results were contrasted to data derived from a previous
PFOA study. PFOS-dependent changes were primarily related to activation
of PPAR[alpha]. No remarkable differences were found between PFOS
and PFOA. Given that PPAR[alpha] signaling is required for neonatal
mortality in PFOA-treated mice but not those exposed to PFOS, the
neonatal mortality observed for PFOS may reflect functional deficits
related to the physical properties of the chemical rather than to
transcript alterations.},
booktitle = {Recent Advances in Perfluoroalkyl Acid Research},
issn = {0890-6238},
keywords = {PFOS, PFOA, PPAR[alpha], Gene profiling, Liver, Lung, Mouse, Fetus},
url = {http://www.sciencedirect.com/science/article/B6TC0-4VJBTP4-1/2/f19a420c932d08360c56e339b5007092}
}
@ARTICLE{Rosen2007,
author = {Rosen, Mitchell B. and Thibodeaux, Julie R. and Wood, Carmen R. and
Zehr, Robert D. and Schmid, Judith E. and Lau, Christopher},
title = {Gene expression profiling in the lung and liver of PFOA-exposed mouse
fetuses},
journal = {Toxicology},
year = {2007},
volume = {239},
pages = {15--33},
number = {1-2},
month = sep,
abstract = {Perfluorooctanoic acid (PFOA) is a stable perfluoroalkyl acid used
to synthesize fluoropolymers during the manufacture of a wide variety
of products. Concerns have been raised over the potential health
effects of PFOA because it is persistent in the environment and can
be detected in blood and other tissues of many animal species, including
humans. PFOA has also been shown to induce growth deficits and mortality
in murine neonates. To better understand the mechanism of PFOA induced
developmental toxicity, lung and liver gene expression profiling
was conducted in PFOA-exposed full-term mouse fetuses. Thirty timed-pregnant
CD-1 mice were orally dosed from gestation days 1-17 with either
0, 1, 3, 5, or 10 mg/(kg day) PFOA in water. At term, fetal lung
and liver were collected, total RNA prepared, and samples pooled
from three fetuses per litter. Five biological replicates consisting
of individual litter samples were then evaluated for each treatment
group using Affymetrix mouse 430_2 microarrays. The expression of
genes related to fatty acid catabolism was altered in both the fetal
liver and lung. In the fetal liver, the effects of PFOA were robust
and also included genes associated with lipid transport, ketogenesis,
glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis,
steroid metabolism, bile acid biosynthesis, phospholipid metabolism,
retinol metabolism, proteosome activation, and inflammation. These
changes are consistent with transactivation of PPAR[alpha], although,
with regard to bile acid biosynthesis and glucose metabolism, non-PPAR[alpha]
related effects were suggested as well. Additional studies will be
needed to more thoroughly address the role of PPAR[alpha], and other
nuclear receptors, in PFOA mediated developmental toxicity.},
issn = {0300-483X},
keywords = {Gene profiling, Fetus, Liver, Lung, Perfluorooctanoic acid, PFOA,
PPAR[alpha]},
url = {http://www.sciencedirect.com/science/article/B6TCN-4P2YWV9-2/2/63aa9b162f1e67986a6563e710141e63}
}
@ARTICLE{Rosenbach2011,
author = {Rosenbach, Alan E. and Koria, Piyush and Goverman, Jeremy and Kotz,
Kenneth T. and Gupta, Amit and Yu, Ming and Fagan, Shawn P. and Irimia,
Daniel and Tompkins, Ronald G.},
title = {Microfluidics for T- Lymphocyte Cell Separation and Inflammation
Monitoring in Burn Patients},
journal = {Clinical and Translational Science},
year = {2011},
volume = {4},
pages = {63--68},
number = {1},
abstract = {Abstract Severe burns result in T lymphocyte specific immunologic
changes. In addition to decreased levels of circulating lymphocytes,
changes in cytokine secretion and receptor expression also take place.
Our finer understanding of the inflammatory response has led to the
development of immune-targeted therapeutics, requiring specialized
gene-expression monitoring. The emerging field of bio-micro-electromechanical
systems can be used to isolate highly pure T lymphocytes in a clinically
relevant and timely manner for downstream genomic analysis. Blood
samples from healthy volunteers and burn-injured patients were introduced
into microfluidic devices developed in our laboratory. Utilizing
cell-affinity chromatography for positive selection of T lymphocytes,
the devices served as a platform for RNA extraction and downstream
cytokine analysis via quantitative real-time polymerase chain reaction
(PCR). From a 0.5-mL whole blood sample, the microfluidic devices
captured highly pure T lymphocytes from healthy volunteers and burn-injured
patients. Cell capture was of sufficient quantity, and extracted
RNA was of sufficient quality, for evaluating the gene expression
of cytokines: interferon-gamma, interleukin-2, interleukin-4, and
interleukin-10. Microfluidics is a useful tool in processing blood
from burn-injured patients. Though in its very early stages of development,
cell-specific information obtained by this platform/technology will
likely be an important component of near-patient molecular diagnostics
and personalized medicine. Clin Trans Sci 2011; Volume 4: 63–68},
doi = {10.1111/j.1752-8062.2010.00255.x},
issn = {1752-8062},
keywords = {antibodies, cytokines, immune system, immunocompromised hosts, lymphocytes,
translational research},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1752-8062.2010.00255.x}
}
@ARTICLE{Rosenbaum2009,
author = {Rosenbaum, James T. and Pasadhika, Sirichai and Crouser, Elliott
D. and Choi, Dongseok and Harrington, Christina A. and Lewis, Jinnell
A. and Austin, Carrie R. and Diebel, Tessa N. and Vance, Emily E.
and Braziel, Rita M. and Smith, Justine R. and Planck, Stephen R.},
title = {Hypothesis: Sarcoidosis is a STAT1-mediated disease},
journal = {Clinical Immunology},
year = {2009},
volume = {132},
pages = {174--183},
number = {2},
month = aug,
abstract = {Immunologic pathways involved in sarcoidosis pathogenesis are largely
unknown. We hypothesized that patients with sarcoidosis have characteristic
mRNA profiles. Microarray analysis of gene expression was done on
peripheral blood (12 patients, 12 controls), lung (6 patients, 6
controls) and lymph node (8 patients, 5 controls). Comparing peripheral
blood from patients with sarcoidosis to controls, 872 transcripts
were upregulated and 1039 were downregulated at > 1.5-fold change
and a significant q value. Several transcripts associated with interferon
and STAT1 were upregulated. Lung and lymph node analyses also showed
dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas
in lymph nodes of patients with sarcoidosis expressed abundant STAT1
and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis.
This novel hypothesis unites seemingly disparate observations with
regard to sarcoidosis including implication of a casual role for
interferons, a suspected infectious trigger, TH1 predominating lymphocytes
in bronchoalveolar lavage, and the association with hypercalcemia.},
issn = {1521-6616},
keywords = {Gene expression profiling, Microarray analysis, Sarcoidosis, Uveitis},
url = {http://www.sciencedirect.com/science/article/B6WCJ-4WBR6J5-1/2/eae94d393e8a4cc365eb1e59dd1549f8}
}
@ARTICLE{Rosenberg2011,
author = {Rosenberg, Brad R and Hamilton, Claire E and Mwangi, Michael M and
Dewell, Scott and Papavasiliou, F Nina},
title = {Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing
targets in transcript 3′ UTRs},
journal = {Nat Struct Mol Biol},
year = {2011},
volume = {18},
pages = {230--236},
number = {2},
month = feb,
comment = {10.1038/nsmb.1975},
issn = {1545-9993},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nsmb.1975}
}
@ARTICLE{Rosenberg2010,
author = {Rosenberg, Martina J. and Wolff, Christina R. and El-Emawy, Ahmed
and Staples, Miranda C. and Perrone-Bizzozero, Nora I. and Savage,
Daniel D.},
title = {Effects of moderate drinking during pregnancy on placental gene expression},
journal = {Alcohol},
year = {2010},
volume = {44},
pages = {673--690},
number = {7-8},
month = nov,
abstract = {Many children adversely affected by maternal drinking during pregnancy
cannot be identified early in life using current diagnostic criteria
for fetal alcohol spectrum disorder (FASD). We conducted a preliminary
investigation to determine whether ethanol-induced alterations in
placental gene expression may have some utility as a diagnostic indicator
of maternal drinking during pregnancy and as a prognostic indicator
of risk for adverse neurobehavioral outcomes in affected offspring.
Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol
solution 4 h each day throughout gestation. Ethanol consumption produced
a mean maternal daily intermittent peak serum ethanol concentration
of 84 mg/dL. Placentas were harvested on gestational day 20 for gene
expression studies. Microarray analysis of more than 28,000 genes
revealed that the expression of 304 known genes was altered twofold
or greater in placenta from ethanol-consuming dams compared with
controls. About 76% of these genes were repressed in ethanol-exposed
placentas. Gene expression changes involved proteins associated with
central nervous system development; organ morphogenesis; immunological
responses; endocrine function; ion homeostasis; and skeletal, cardiovascular,
and cartilage development. To date, quantitative real-time polymerase
chain reaction analysis has confirmed significant alterations in
gene expression for 22 genes, including genes encoding for three
calcium binding proteins, two matrix metalloproteinases, the cannabinoid
1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase 2,
11-[beta] hydroxysteroid dehydrogenase 2, placental growth factor,
transforming growth factor alpha, gremlin 1, and epithelial growth
factor (EGF)-containing extracellular matrix protein. These results
suggest that the expression of a sufficiently large number of placental
mRNAs is altered after moderate drinking during pregnancy to warrant
more detailed investigation of the placenta as a biomarker system
for maternal drinking during pregnancy and as an early indicator
of FASD. Furthermore, these results provide new insights into novel
mechanisms on how ethanol may directly or indirectly mediate its
teratogenic effects through alterations in placental function during
pregnancy.},
booktitle = {Special Issue on Fetal Alcohol Spectrum Disorders: Diagnosis and
Intervention},
issn = {0741-8329},
keywords = {Fetal alcohol spectrum disorder, Ethanol, Placenta, Microarray, qRT-PCR,
Biomarker},
url = {http://www.sciencedirect.com/science/article/pii/S0741832909001694}
}
@ARTICLE{Rosic2010,
author = {Rosic, Nedeljka N. and Pernice, Mathieu and Dunn, Simon and Dove,
Sophie and Hoegh-Guldberg, Ove},
title = {Novel cytochrome P450 genes from the symbiotic dinoflagellates of
reef-building corals: Differential regulation by heat stress},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {Epub},
pages = {AEM.02984-09--},
month = mar,
abstract = {Exposure to heat stress has been recognized as one of the major factors
leading to the breakdown of the coral-algal symbiosis and coral bleaching.
Here, we report the presence of three new Cytochrome P450 (CYP) genes
from reef-building coral endosymbiont Symbiodinium (C3) and changes
in their expression during exposure to severe and moderate heat stress
conditions. The sequence analysis of CYP C-terminal region and two
conserved domains, "PERF" and "heme-binding", confirmed the separate
identity of analysed CYP genes. In order to explore the effect of
different heat stress scenarios, samples of the scleractinian coral
Acropora millepora were exposed to elevated temperatures incrementally
over 18 h (rapid thermal stress) and 120 h (gradual thermal stress).
After 18 h of gradual heating and at 26{degrees}C, the Symbiodinium
CYPs mRNA pool increased by approximately 30%, whilst a further rise
in temperature of 6{degrees}C above average sea temperature (29{degrees}C,
after 72 h) increased CYPs expression between 2- and 4-fold. Both
rapid and gradual heat stress scenarios at 32{degrees}C led to a
50% to 90% decrease in CYP genes transcript abundance. Consequently,
initial expression up-regulation of CYPs at moderately elevated temperatures
(26{degrees}C and 29{degrees}C) was followed by decrease in expression
under the higher thermal stress conditions at 32{degrees}C. These
findings indicate the production of chemical stressors and/or the
transcriptional factors within the coral-algal symbiosis under heat
stress that regulate the expression of genes such as cytochrome P450
monoxygenases that are in the first line of an organism's chemical
defence.},
url = {http://aem.asm.org/cgi/content/abstract/AEM.02984-09v1}
}
@ARTICLE{Rosic2010a,
author = {Rosic, Nedeljka N. and Pernice, Mathieu and Dunn, Simon and Dove,
Sophie and Hoegh-Guldberg, Ove},
title = {Differential Regulation by Heat Stress of Novel Cytochrome P450 Genes
from the Dinoflagellate Symbionts of Reef-Building Corals},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {2823--2829},
number = {9},
month = may,
abstract = {Exposure to heat stress has been recognized as one of the major factors
leading to the breakdown of the coral-alga symbiosis and coral bleaching.
Here, we describe the presence of three new cytochrome P450 (CYP)
genes from the reef-building coral endosymbiont Symbiodinium (type
C3) and changes in their expression during exposure to severe and
moderate heat stress conditions. Sequence analysis of the CYP C-terminal
region and two conserved domains, the "PERF" and "heme-binding" domains,
confirmed the separate identities of the CYP genes analyzed. In order
to explore the effects of different heat stress scenarios, samples
of the scleractinian coral Acropora millepora were exposed to elevated
temperatures incrementally over an 18-h period (rapid thermal stress)
and over a 120-h period (gradual thermal stress). After 18 h of gradual
heating and incubation at 26{degrees}C, the Symbiodinium CYP mRNA
pool was approximately 30% larger, while a further 6{degrees}C increase
to a temperature above the average sea temperature (29{degrees}C
after 72 h) resulted in a 2- to 4-fold increase in CYP expression.
Both rapid heat stress and gradual heat stress at 32{degrees}C resulted
in 50% to 90% decreases in CYP gene transcript abundance. Consequently,
the initial upregulation of expression of CYP genes at moderately
elevated temperatures (26{degrees}C and 29{degrees}C) was followed
by a decrease in expression under the greater thermal stress conditions
at 32{degrees}C. These findings indicate that in the coral-alga symbiosis
under heat stress conditions there is production of chemical stressors
and/or transcriptional factors that regulate the expression of genes,
such as the genes encoding cytochrome P450 monooxygenases, that are
involved in the first line of an organism's chemical defense.},
url = {http://aem.asm.org/cgi/content/abstract/76/9/2823}
}
@ARTICLE{Rosinski-Chupin2007,
author = {Rosinski-Chupin, Isabelle and Briolay, Jérôme and Brouilly, Patrick
and Perrot, Sylvie and Gomez, Shawn M. and Chertemps, Thomas and
Roth, Charles W. and Keime, Céline and Gandrillon, Olivier and Couble,
Pierre and Brey, Paul T.},
title = {SAGE analysis of mosquito salivary gland transcriptomes during Plasmodium
invasion},
journal = {Cellular Microbiology},
year = {2007},
volume = {9},
pages = {708--724},
number = {3},
abstract = {Summary Invasion of the vector salivary glands by Plasmodium is a
critical step for malaria transmission. To describe salivary gland
cellular responses to sporozoite invasion, we have undertaken the
analysis of Anopheles gambiae salivary gland transcriptome using
Serial Analysis of Gene Expression (SAGE). Statistical analysis of
the more than 160Â 000 sequenced tags generated from four libraries,
two from glands infected by Plasmodium berghei, two from glands of
controls, revealed that at least 57 Anopheles genes are differentially
expressed in infected salivary glands. Among the 37 immune-related
genes identified by SAGE tags, four (Defensin1, GNBP, Serpin6 and
Cecropin2) were found to be upregulated during salivary gland invasion,
while five genes encoding small secreted proteins display induction
patterns strongly reminiscent of that of Cecropin2. Invasion by Plasmodium
has also an impact on the expression of genes involved in transport,
lipid and energy metabolism, suggesting that the sporozoite may exploit
the metabolism of its host. In contrast, protein composition of saliva
is predicted to be only slightly modified after infection. This study,
which is the first transcriptome analysis of the salivary gland response
to Plasmodium infection, provides a basis for a better understanding
of Plasmodium/Anopheles salivary gland interactions.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2006.00822.x}
}
@ARTICLE{Rosman2008,
author = {Rosman, Diana S. and Phukan, Sharbani and Huang, Chiang-Ching and
Pasche, Boris},
title = {TGFBR1*6A Enhances the Migration and Invasion of MCF-7 Breast Cancer
Cells through RhoA Activation},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {1319--1328},
number = {5},
month = mar,
abstract = {TGFBR1*6A is a common hypomorphic variant of the type 1 transforming
growth factor {beta} receptor (TGFBR1), which has been associated
with increased cancer risk in some studies. Although TGFBR1*6A is
capable of switching TGF-{beta} growth-inhibitory signals into growth-stimulatory
signals when stably transfected into MCF-7 breast cancer cells, the
biological effects of TGFBR1*6A are largely unknown. To broadly explore
the potential oncogenic properties of TGFBR1*6A, we assessed its
effects on NIH-3T3 cells as well as its effect on the migration and
invasion of MCF-7 cells. We found that TGFBR1*6A has decreased oncogenic
properties compared with TGFBR1. However, TGFBR1*6A significantly
enhances MCF-7 cell migration and invasion in a TGF-{beta} signaling-independent
manner. Gene expression profiling studies identified two down-regulated
genes involved in cell migration and invasion: ARHGAP5, encoding
ARHGAP5, and FN1, encoding fibronectin-1 (FN1). ARHGAP5 and FN1 expression
was similarly down-regulated in MCF-7 cells stably transfected with
a kinase-inactivated TGFBR1*6A construct. Functional assays show
that TGFBR1*6A-mediated decreased ARHGAP5 expression is associated
with higher RhoA activation, a crucial mediator of cell migration.
Extracellular signal-regulated kinase (ERK) activation is also higher
in cells that harbor the TGFBR1*6A allele. We conclude that TGFBR1*6A
is not an oncogene but enhances MCF-7 cell migration and invasion
through RhoA and ERK pathway activation and down-regulates two crucial
mediators of this phenotype. These results provide the first evidence
that TGFBR1*6A may contribute to cancer progression in a TGF-{beta}
signaling-independent manner. [Cancer Res 2008;68(5):1319-28]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/5/1319}
}
@ARTICLE{Ross2011a,
author = {Ross, Ashley E. and Marchionni, Luigi and Phillips, Timothy M. and
Miller, Rebecca M. and Hurley, Paula J. and Simons, Brian W. and
Salmasi, Amirali H. and Schaeffer, Anthony J. and Gearhart, John
P. and Schaeffer, Edward M.},
title = {Molecular Effects of Genistein on Male Urethral Development},
journal = {The Journal of Urology},
year = {2011},
volume = {185},
pages = {1894--1899},
number = {5},
month = may,
abstract = {Purpose The increasing incidence of hypospadias is partly attributed
to increased gestational exposure to endocrine disruptors. We investigated
the effects of genistein, the primary phytoestrogen in soy, on the
molecular program of male urethral development.Materials and Methods
Female mice were fed diets supplemented with genistein (500 mg/kg
diet) or control diets before breeding and throughout gestation.
Urethras from embryonic day 17.5 male fetuses were harvested, and
RNA was prepared, amplified, labeled and hybridized on whole genome
microarrays. Data were analyzed using packages from the R/Bioconductor
project. Immunohistochemical analysis and immunoblotting were used
to confirm the activity of MAPK and the presence of Ntrk1 and Ntrk2
during urethral development.Results Gestational exposure to genistein
altered the urethral expression of 277 genes (p <0.008). Among the
most affected were hormonally regulated genes, including IGFBP-1,
Kap and Rhox5. Differentially expressed genes were grouped into functional
pathways of cell proliferation, adhesion, apoptosis and tube morphogenesis
(p <0.0001), and were enriched for members of the MAPK (p <0.00001)
and TGF-[beta] (p <0.01) signaling cascades. Differentially expressed
genes preferentially contained ELK1, Myc/Max, FOXO, HOX and ER control
elements. The MAPK pathway was active, and its upstream genistein
affected tyrosine kinase receptors Ntrk1 and Ntrk2 were present in
the developing male urethra.Conclusions Gestational exposure to genistein
contributes to hypospadias by altering pathways of tissue morphogenesis,
cell proliferation and cell survival. In particular, genes in the
MAPK and TGF-[beta] signaling pathways and those controlled by FOXO,
HOX and ER transcription factors are disrupted.},
issn = {0022-5347},
keywords = {endocrine disruptors, gene expression profiling, genistein, hypospadias},
url = {http://www.sciencedirect.com/science/article/pii/S0022534710054376}
}
@ARTICLE{Ross2007,
author = {Ross, Andrea J. and Dailey, Lisa A. and Brighton, Luisa E. and Devlin,
Robert B.},
title = {Transcriptional Profiling of Mucociliary Differentiation in Human
Airway Epithelial Cells},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2007},
volume = {37},
pages = {169--185},
number = {2},
month = aug,
abstract = {When cultured at an air-liquid interface (ALI) in the appropriate
medium, primary human airway epithelial cells form a polarized, pseudostratified
epithelium composed of ciliated and mucus-secreting cells. This culture
system provides a useful tool for the in vitro study of airway epithelial
biology and differentiation. We have performed microarray analysis
on ALI cultures of human bronchial epithelial cells (HBECs) grown
over a 28-d period to identify genes involved in mucociliary differentiation.
We identified over 2,000 genes that displayed statistically significant
2-fold or greater changes in expression during the time course. Of
the genes showing the largest increases, many are involved in processes
associated with airway epithelial biology, such as cell adhesion,
immunity, transport, and cilia formation; however, many novel genes
were also identified. We compared our results with data from proteomic
analyses of the ciliary axoneme and identified candidate genes that
may have roles in cilia formation or function. Gene networks were
generated using Ingenuity Pathways Analysis (Ingenuity Systems, Redwood
City, CA) to identify signaling pathways involved in mucociliary
cell differentiation or function. Networks containing genes involved
in TGF-[beta], WNT/[beta]-catenin, and epidermal growth factor receptor
(EGFR) pathways were identified, suggesting potential roles for these
families in airway epithelia. Microarray results were validated by
real-time RT-PCR for a number of representative genes. This work
has provided extensive information about gene expression changes
during differentiation of airway epithelial cells, and will be a
useful resource for researchers interested in respiratory function,
pathology, and toxicology.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/37/2/169}
}
@ARTICLE{Ross2011,
author = {Ross, Heather A. and Morris, Wayne L. and Ducreux, Laurence J.M.
and Hancock, Robert D. and Verrall, Susan R. and Morris, Jenny A
and Tucker, Gregory A. and Stewart, Derek and Hedley, Pete E. and
McDougall, Gordon J. and Taylor, Mark A.},
title = {Pectin engineering to modify product quality in potato},
journal = {Plant Biotechnology Journal},
year = {2011},
volume = {9},
pages = {848--856},
number = {8},
abstract = {Although processed potato tuber texture is an important trait that
influences consumer preference, a detailed understanding of tuber
textural properties at the molecular level is lacking. Previous work
has identified tuber pectin methyl esterase (PME) activity as a potential
factor impacting on textural properties, and the expression of a
gene encoding an isoform of PME (PEST1) was associated with cooked
tuber textural properties. In this study, a transgenic approach was
undertaken to investigate further the impact of the PEST1 gene. Antisense
and over-expressing potato lines were generated. In over-expressing
lines, tuber PME activity was enhanced by up to 2.3-fold; whereas
in antisense lines, PME activity was decreased by up to 62%. PME
isoform analysis indicated that the PEST1 gene encoded one isoform
of PME. Analysis of cell walls from tubers from the over-expressing
lines indicated that the changes in PME activity resulted in a decrease
in pectin methylation. Analysis of processed tuber texture demonstrated
that the reduced level of pectin methylation in the over-expressing
transgenic lines was associated with a firmer processed texture.
Thus, there is a clear link between PME activity, pectin methylation
and processed tuber textural properties.},
doi = {10.1111/j.1467-7652.2011.00591.x},
issn = {1467-7652},
keywords = {cell wall, pectin, pectin methyl esterase, potato, texture, tuber},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1467-7652.2011.00591.x}
}
@ARTICLE{Ross2010,
author = {Ross, Jeffrey A. and Blackman, Carl F. and Thai, Sheau-Fung and Li,
Zhiguang and Kohan, Michael and Jones, Carlton P. and Chen, Tao},
title = {A potential microRNA signature for tumorigenic conazoles in mouse
liver},
journal = {Mol. Carcinog.},
year = {2010},
volume = {49},
pages = {320--323},
number = {4},
abstract = {Abstract 10.1002/mc.20620.abs Triadimefon, propiconazole, and myclobutanil
are conazoles, an important class of agricultural fungicides. Triadimefon
and propiconazole are mouse liver tumorigens, while myclobutanil
is not. As part of a coordinated study to understand the molecular
determinants of conazole tumorigenicity, we analyzed the microRNA
expression levels in control and conazole-treated mice after 90 d
of administration in feed. MicroRNAs (miRNAs) are small noncoding
RNAs composed of approximately 19–24 nucleotides in length, and
have been shown to interact with mRNA (usually 3′ UTR) to suppress
its expression. MicroRNAs play a key role in diverse biological processes,
including development, cell proliferation, differentiation, and apoptosis.
Groups of mice were fed either control diet or diet containing 1800 ppm
triadimefon, 2500 ppm propiconazole, or 2000 ppm myclobutanil.
MicroRNA was isolated from livers and analyzed using Superarray whole
mouse genome miRNA PCR arrays from SABioscience. Data were analyzed
using the significance analysis of microarrays (SAM) procedure. We
identified those miRNAs whose expression was either increased or
decreased relative to untreated controls with q ≤ 0.01. The
tumorigenic conazoles induced many more changes in miRNA expression
than the nontumorigenic conazole. A group of 19 miRNAs was identified
whose expression was significantly altered in both triadimefon- and
propiconazole-treated animals but not in myclobutanil-treated animals.
All but one of the altered miRNAs were downregulated compared to
controls. This pattern of altered miRNA expression may represent
a signature for tumorigenic conazole exposure in mouse liver after
90 d of treatment. Published 2010 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {microRNA, conazole, fungicides, tumorigenicity, expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20620}
}
@ARTICLE{Ross2009,
author = {Ross, Jeffrey S. and Slodkowska, Elzbieta A.},
title = {Circulating and Disseminated Tumor Cells in the Management of Breast
Cancer},
journal = {Am J Clin Pathol},
year = {2009},
volume = {132},
pages = {237--245},
number = {2},
month = aug,
abstract = {Despite the advances in early detection and treatment of cancer, patients
continue to die of the disease even when they seek care at an early
stage. For patients with breast cancer, it is now possible to detect
circulating tumor cells (CTCs) in the bloodstream and disseminated
tumor cells (DTCs) in the bone marrow by using immunocytochemical
and molecular methods. CTCs and DTCs have been found to share similar
genotypic and phenotypic characteristics with so-called breast cancer
stem cells, a finding that could potentially explain the eventual
relapse of disease in a patient previously considered to have been
cured by primary therapy. In some studies, the presence of CTCs or
DTCs at the time of diagnosis of breast cancer is an independent
adverse prognostic variable. However, before CTC/DTC testing can
achieve standard-of-care status, there must be improvement in the
sensitivity, precision, and reproducibility of the detection methods.},
url = {http://ajcp.ascpjournals.org/cgi/content/abstract/132/2/237}
}
@ARTICLE{Ross2009a,
author = {Ross, Pamela K. and Woods, Courtney G. and Bradford, Blair U. and
Kosyk, Oksana and Gatti, Daniel M. and Cunningham, Michael L. and
Rusyn, Ivan},
title = {Time-course comparison of xenobiotic activators of CAR and PPAR[alpha]
in mouse liver},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {235},
pages = {199--207},
number = {2},
month = mar,
abstract = {Constitutive androstane receptor (CAR) and peroxisome proliferator
activated receptor (PPAR)[alpha] are transcription factors known
to be primary mediators of liver effects, including carcinogenesis,
by phenobarbital-like compounds and peroxisome proliferators, respectively,
in rodents. Many similarities exist in the phenotypes elicited by
these two classes of agents in rodent liver, and we hypothesized
that the initial transcriptional responses to the xenobiotic activators
of CAR and PPAR[alpha] will exhibit distinct patterns, but at later
time-points these biological pathways will converge. In order to
capture the global transcriptional changes that result from activation
of these nuclear receptors over a time-course in the mouse liver,
microarray technology was used. First, differences in basal expression
of liver genes between C57Bl/6J wild-type and Car-null mice were
examined and 14 significantly differentially expressed genes were
identified. Next, mice were treated with phenobarbital (100 mg/kg
by gavage for 24 h, or 0.085% w/w diet for 7 or 28 days), and liver
gene expression changes with regards to both time and treatment were
identified. While several pathways related to cellular proliferation
and metabolism were affected by phenobarbital in wild-type mice,
no significant changes in gene expression were found over time in
the Car-nulls. Next, we determined commonalities and differences
in the temporal response to phenobarbital and WY-14,643, a prototypical
activator of PPAR [alpha]. Gene expression signatures from livers
of wild-type mice C57Bl6/J mice treated with PB or WY-14,643 were
compared. Similar pathways were affected by both compounds; however,
considerable time-related differences were present. This study establishes
common gene expression fingerprints of exposure to activators of
CAR and PPAR[alpha] in rodent liver and demonstrates that despite
similar phenotypic changes, molecular pathways differ between classes
of chemical carcinogens.},
issn = {0041-008X},
keywords = {Kupffer cells, PPAR[alpha], Toxicogenomics, Microarrays},
url = {http://www.sciencedirect.com/science/article/B6WXH-4V70R7B-1/2/29a7b8dde8b3e8e272262c01dade112f}
}
@ARTICLE{Ross2005,
author = {Ross, T. L. and Merz, W. G. and Farkosh, M. and Carroll, K. C.},
title = {Comparison of an Automated Repetitive Sequence-Based PCR Microbial
Typing System to Pulsed-Field Gel Electrophoresis for Analysis of
Outbreaks of Methicillin-Resistant Staphylococcus aureus},
journal = {J. Clin. Microbiol.},
year = {2005},
volume = {43},
pages = {5642--5647},
number = {11},
month = nov,
abstract = {Rapid and sensitive methods for accurate strain delineation are essential
for monitoring and preventing transmission of methicillin-resistant
Staphylococcus aureus (MRSA). Pulsed-field gel electrophoresis (PFGE)
has been the standard technique for strain typing most bacterial
species including MRSA. The goal of this study was to compare the
performance of the DiversiLab microbial typing system (Bacterial
BarCodes, Inc., Houston, TX) (rep-PCR) to that of PFGE for typing
MRSA isolates from five well-defined outbreaks. The DiversiLab rep-PCR
assay is a rapid, semiautomated method based on PCR amplification
of specific regions between noncoding repetitive sequences in the
bacterial genome. rep-PCR was performed according to the manufacturer's
recommendations, and the results were analyzed and dendrograms were
generated using the DiversiLab analysis software (version 2.1.66a).
PFGE was performed and interpreted according to published procedures.
rep-PCR results using similarity indices (SI) of 80%, 85%, and 90%
were compared to PFGE analysis. In addition, intra- and interrun
reproducibility was determined for rep-PCR. Overall, correct assignment
to outbreak versus nonoutbreak clusters occurred for 91 of 109 isolates
(85% agreement) when using a SI of 85%. For each specific outbreak,
concordance between rep-PCR and PFGE ranged from 73% to 100%. There
were 18 discrepant results (17%). Fourteen isolates were unique by
PFGE, but they were placed in clusters by rep-PCR; the other 4 were
placed in clusters different from those assigned by PFGE. Intra-
and interrun reproducibility was excellent. Times to results were
12 to 24 h for rep-PCR compared to 2 to 4 days for PFGE. Rapid, standardized
results and excellent reproducibility make rep-PCR a valuable tool
for use in MRSA investigations. However, since rep-PCR was less discriminatory
than PFGE, we recommend that it be used to screen isolates, followed
by testing isolates which share the same rep-PCR pattern with a more
sensitive method, such as PFGE or multilocus sequence typing.},
url = {http://jcm.asm.org/cgi/content/abstract/43/11/5642}
}
@ARTICLE{Ross-Macdonald2008,
author = {Ross-Macdonald, Petra and de Silva, Heshani and Guo, Qi and Xiao,
Hong and Hung, Chen-Yi and Penhallow, Becky and Markwalder, Jay and
He, Liqi and Attar, Ricardo M. and Lin, Tai-an and Seitz, Steven
and Tilford, Charles and Wardwell-Swanson, Judith and Jackson, Donald},
title = {Identification of a nonkinase target mediating cytotoxicity of novel
kinase inhibitors},
journal = {Mol. Cancer Ther.},
year = {2008},
volume = {7},
pages = {3490--3498},
number = {11},
month = nov,
abstract = {In developing inhibitors of the LIM kinases, the initial lead molecules
combined potent target inhibition with potent cytotoxic activity.
However, as subsequent compounds were evaluated, the cytotoxic activity
separated from inhibition of LIM kinases. A rapid determination of
the cytotoxic mechanism and its molecular target was enabled by integrating
data from two robust core technologies. High-content assays and gene
expression profiling both indicated an effect on microtubule stability.
Although the cytotoxic compounds are still kinase inhibitors, and
their structures did not predict tubulin as an obvious target, these
results provided the impetus to test their effects on microtubule
polymerization directly. Unexpectedly, we confirmed tubulin itself
as a molecular target of the cytotoxic kinase inhibitor compounds.
This general approach to mechanism of action questions could be extended
to larger data sets of quantified phenotypic and gene expression
data. [Mol Cancer Ther 2008;7(11):3490-8]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/7/11/3490}
}
@ARTICLE{Ross-Macdonald2011,
author = {Petra Ross-Macdonald and Heshani de Silva and Vishal Patel and Amy
Truong and Aiqing He and Isaac Neuhaus and Charles Tilford and RuiRu
Ji and Nathan Siemers and Ann Greer and Joan Carboni and Marco Gottardis
and Krista Menard and Frank Lee and Marco Dodier and David Frennesson
and Anthony Sampognaro and Mark Saulnier and George Trainor and Dolatrai
Vyas and Kurt Zimmermann and Mark Wittman},
title = {Biochemical and transcriptional profiling to triage additional activities
in a series of IGF-1R/IR inhibitors},
journal = {Bioorganic \& Medicinal Chemistry},
year = {2011},
pages = { - },
number = {0},
abstract = {Therapeutic development of a targeted agent involves a series of decisions
over additional activities that may be ignored, eliminated or pursued.
This paper details the concurrent application of two methods that
provide a spectrum of information about the biological activity of
a compound: biochemical profiling on a large panel of kinase assays
and transcriptional profiling of mRNA responses. Our mRNA profiling
studies used a full dose range, identifying subsets of transcriptional
responses with differing EC50s which may reflect distinct targets.
Profiling data allowed prioritization for validation in xenograft
models, generated testable hypotheses for active compounds, and informed
decisions on the general utility of the series.},
doi = {10.1016/j.bmc.2011.10.090},
issn = {0968-0896},
keywords = {Kinase},
url = {http://www.sciencedirect.com/science/article/pii/S0968089611009175}
}
@ARTICLE{Rosseau2007,
author = {Rosseau, Simone and Hocke, Andreas and Mollenkopf, Hans and Schmeck,
Bernd and Suttorp, Norbert and Kaufmann, Stefan H. E. and Zerrahn,
Jens},
title = {Comparative transcriptional profiling of the lung reveals shared
and distinct features of Streptococcus pneumoniae and influenza A
virus infection},
journal = {Immunology},
year = {2007},
volume = {120},
pages = {380--391},
number = {3},
abstract = {Summary Pneumonia is the most common cause of death from infectious
disease in the western hemisphere. Pathophysiological and protective
processes are initiated by pattern recognition of microbial structures.
To provide the molecular framework for a better understanding of
processes relevant to host defence in pneumonia, we performed pulmonary
transcriptome analysis in mice infected with the major bacterial
and viral agents of community-acquired pneumonia, Streptococcus pneumoniae
and influenza A virus. We detected differential expression of 1300
genes after infection with either pathogen. Of these, approximately
36% or 30% were specific for pneumococcal or influenza infection,
respectively, yielding pathogen-specific as well as shared inflammatory
transcriptional signatures. These results not only reveal a differential
response on the cytokine and chemokine levels but also emphasize
the important role of genes implicated in regulation and fine tuning
of inflammation. As one, albeit unexpected, key feature of pneumococcal
pneumonia we discovered down-regulation of B-cell responses, probably
reflecting a pneumococcal virulence strategy. The pathophysiological
consequences of influenza A virus infection were reflected by the
emerging protective T-cell response and differential induction of
genes involved in tissue regeneration and proliferation. These data
provide new insights into pathogenesis of the most common forms of
pneumonia, highlighting the value of transcriptional profiling for
the elucidation of underlying mechanisms.},
issn = {1365-2567},
keywords = {influenza, lung, pneumococci, pneumonia, transcriptome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2006.02514.x}
}
@ARTICLE{Rossel2007,
author = {Rossel, Jan Bart and Wilson, Pip B. and Hussain, Dawar and Woo, Nick
S. and Gordon, Matthew J. and Mewett, Osman P. and Howell, Katharine
A. and Whelan, Jim and Kazan, Kemal and Pogson, Barry J.},
title = {Systemic and Intracellular Responses to Photooxidative Stress in
Arabidopsis},
journal = {PLANT CELL},
year = {2007},
volume = {19},
pages = {4091--4110},
number = {12},
month = dec,
abstract = {As the sun tracks daily through the sky from east to west, different
parts of the canopy are exposed to high light (HL). The extent of
and mechanisms by which a systemic acquired acclimation (SAA) response
might preacclimate shaded leaves that will be subsequently exposed
to full sunlight is largely undefined. We investigated the role of
an Arabidopsis thaliana zinc finger transcription factor, ZAT10,
in SAA. ZAT10 overexpression resulted in enhanced tolerance to photoinhibitory
light and exogenous H2O2, increased expression of antioxidative genes
whose products are targeted to multiple subcellular compartments.
Partial HL exposure of a leaf or leaves rapidly induced ZAT10 mRNA
in distal, shaded photosynthetic tissues, including the floral stem,
cauline leaves, and rosette, but not in roots. Fully 86% of fivefold
HL-upregulated and 71% of HL-downregulated genes were induced and
repressed, respectively, in distal, shaded leaves. Between 15 and
23% of genes whose expression changed in the HL and/or distal tissues
were coexpressed in the ZAT10 overexpression plants, implicating
ZAT10 in modulating the expression of SAA-regulated genes. The SAA
response was detectable in plants with mutations in abscisic acid,
methyl jasmonate, or salicylic acid synthesis or perception, and
systemic H2O2 diffusion was not detected. Hence, SAA is distinct
from pathogen-stimulated systemic acquired resistance and apparently
involves a novel signal or combination of signals that preacclimate
photosynthetic tissues to HL.},
url = {http://www.plantcell.org/cgi/content/abstract/19/12/4091}
}
@ARTICLE{Rosser2009,
author = {Rosser, Charles J. and Liu, Li and Sun, Yijun and Villicana, Patrick
and McCullers, Molly and Porvasnik, Stacy and Young, Paul R. and
Parker, Alexander S. and Goodison, Steve},
title = {Bladder Cancer-Associated Gene Expression Signatures Identified by
Profiling of Exfoliated Urothelia},
journal = {Cancer Epidemiol. Biomarkers Prev.},
year = {2009},
volume = {18},
pages = {444--453},
number = {2},
month = feb,
abstract = {Bladder cancer is the fifth most commonly diagnosed malignancy in
the United States and one of the most prevalent worldwide. It harbors
a probability of recurrence of >50%; thus, rigorous, long-term surveillance
of patients is advocated. Flexible cystoscopy coupled with voided
urine cytology is the primary diagnostic approach, but cystoscopy
is an uncomfortable, invasive procedure and the sensitivity of voided
urine cytology is poor in all but high-grade tumors. Thus, improvements
in noninvasive urinalysis assessment strategies would benefit patients.
We applied gene expression microarray analysis to exfoliated urothelia
recovered from bladder washes obtained prospectively from 46 patients
with subsequently confirmed presence or absence of bladder cancer.
Data from microarrays containing 56,000 targets was subjected to
a panel of statistical analyses to identify bladder cancer-associated
gene signatures. Hierarchical clustering and supervised learning
algorithms were used to classify samples on the basis of tumor burden.
A differentially expressed geneset of 319 gene probes was associated
with the presence of bladder cancer (P < 0.01), and visualization
of protein interaction networks revealed vascular endothelial growth
factor and angiotensinogen as pivotal factors in tumor cells. Supervised
machine learning and a cross-validation approach were used to build
a 14-gene molecular classifier that was able to classify patients
with and without bladder cancer with an overall accuracy of 76%.
Our results show that it is possible to achieve the detection of
bladder cancer using molecular signatures present in exfoliated tumor
urothelia. Further investigation and validation of the cancer-associated
profiles may reveal important biomarkers for the noninvasive detection
and surveillance of bladder cancer. (Cancer Epidemiol Biomarkers
Prev 2009;18(2):444-53)},
url = {http://cebp.aacrjournals.org/cgi/content/abstract/18/2/444}
}
@ARTICLE{Rossetti2011,
author = {Rossetti, C.A. and Galindo, C.L. and Everts, R.E. and Lewin, H.A.
and Garner, H.R. and Adams, L.G.},
title = {Comparative analysis of the early transcriptome of Brucella abortus
- Infected monocyte-derived macrophages from cattle naturally resistant
or susceptible to brucellosis},
journal = {Research in Veterinary Science},
year = {2011},
volume = {91},
pages = {40-51},
abstract = {Brucellosis is a worldwide zoonotic infectious disease that has a
significant economic impact on animal production and human public
health. We characterized the gene expression profile of B. abortus-infected
monocyte-derived macrophages (MDMs) from naïve cattle naturally resistant
(R) or susceptible (S) to brucellosis using a cDNA microarray technology.
Our data indicate that (1) B. abortus induced a slightly increased
genome activation in R MDMs and a down-regulated transcriptome in
S MDMs, during the onset of infection, (2) R MDMs had the ability
to mount a type 1 immune response against B. abortus infection which
was impaired in S cells, and (3) the host cell activity was not altered
after 12 h post-B. abortus infection in R MDMs while the cell cycle
was largely arrested in infected S MDMs at 12 h p.i. These results
contribute to an improved understanding of how host responses may
be manipulated to prevent infection by brucellae.},
issn = {0034-5288},
keywords = {Brucella, Macrophages, Cattle, Resistance, Microarray},
url = {http://www.sciencedirect.com/science/article/pii/S0034528810003073}
}
@ARTICLE{Rossetti2009,
author = {Rossetti, Carlos and Galindo, Cristi and Lawhon, Sara and Garner,
Harold and Adams, L Garry},
title = {Brucella melitensis global gene expression study provides novel information
on growth phase-specific gene regulation with potential insights
for understanding Brucella:host initial interactions},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {81},
number = {1},
abstract = {BACKGROUND:Brucella spp. are the etiological agents of brucellosis,
a zoonotic infectious disease that causes abortion in animals and
chronic debilitating illness in humans. Natural Brucella infections
occur primarily through an incompletely defined mechanism of adhesion
to and penetration of mucosal epithelium. In this study, we characterized
changes in genome-wide transcript abundance of the most and the least
invasive growth phases of B. melitensis cultures to HeLa cells, as
a preliminary approach for identifying candidate pathogen genes involved
in invasion of epithelial cells.RESULTS:B. melitensis at the late
logarithmic phase of growth are more invasive to HeLa cells than
mid-logarithmic or stationary growth phases. Microarray analysis
of B. melitensis gene expression identified 414 up- and 40 down-regulated
genes in late-log growth phase (the most invasive culture) compared
to the stationary growth phase (the least invasive culture). As expected,
the majority of up-regulated genes in late-log phase cultures were
those associated with growth, including DNA replication, transcription,
translation, intermediate metabolism, energy production and conversion,
membrane transport, and biogenesis of the cell envelope and outer
membrane; while the down-regulated genes were distributed among several
functional categories.CONCLUSION:This Brucella global expression
profile study provides novel information on growth phase-specific
gene expression. Further characterization of some genes found differentially
expressed in the most invasive culture will likely bring new insights
into the initial molecular interactions between Brucella and its
host.},
doi = {10.1186/1471-2180-9-81},
issn = {1471-2180},
pubmedid = {19419566},
url = {http://www.biomedcentral.com/1471-2180/9/81}
}
@ARTICLE{Rossi2010,
author = {Rossi, L. and Lapini, I. and Magi, A. and Pratesi, G. and Lavitrano,
M. and Biasi, G.M. and Pulli, R. and Pratesi, C. and Abbate, R. and
Giusti, B.},
title = {Carotid Artery Disease: Novel Pathophysiological Mechanisms Identified
by Gene-expression Profiling of Peripheral Blood},
journal = {Eur J Vasc Endovasc Surg},
year = {2010},
volume = {40},
pages = {549--558},
number = {5},
month = nov,
abstract = {The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms
underlying the different localisation of the atherosclerotic lesions
remains poorly understood. We used microarray technology to identify
novel systemic mediators that could contribute to CAS pathogenesis.
Moreover, we compared gene-expression profile of CAS with that of
patients affected by abdominal aortic aneurysm (AAA), previously
published by our group. By global gene-expression profiling in a
pool of 10 CAS patients and 10 matched controls, we found 82 genes
differentially expressed. Validation study in pools used for profiling
and replication study in larger numbers of CAS patients (n = 40)
and controls (n = 40) of 14 genes by real-time polymerase chain
reaction (RT-PCR) confirmed microarray results. Fourteen out of 82
genes were similarly expressed in AAA patients. Gene ontology analysis
identified a statistically significant enrichment in CAS of differentially
expressed transcripts involved in immune response and oxygen transport.
Whereas alteration of oxygen transport is a common tract of the two
localisations, alteration of immune response in CAS and of lipid
metabolic process in AAA represents distinctive tracts of the two
atherosclerotic diseases. We describe the systemic gene-expression
profile of CAS, which provides an extensive list of potential molecular
markers.},
issn = {1078-5884},
keywords = {Carotid artery stenosis, Abdominal aortic aneurysm, Gene-expression,
Immune response, Whole blood},
publisher = {Elsevier},
refid = {S1078-5884(10)00432-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1078588410004326?showall=true}
}
@ARTICLE{Rossi2007,
author = {Rossi, Lara and Manfredini, Rossella and Bertolini, Francesco and
Ferrari, Davide and Fogli, Miriam and Zini, Roberta and Salati, Simona
and Salvestrini, Valentina and Gulinelli, Sara and Adinolfi, Elena
and Ferrari, Sergio and Di Virgilio, Francesco and Baccarani, Michele
and Lemoli, Roberto M.},
title = {The extracellular nucleotide UTP is a potent inducer of hematopoietic
stem cell migration},
journal = {Blood},
year = {2007},
volume = {109},
pages = {533--542},
number = {2},
month = jan,
abstract = {Homing and engraftment of hematopoietic stem cells (HSCs) to the bone
marrow (BM) involve a complex interplay between chemokines, cytokines,
and nonpeptide molecules. Extracellular nucleotides and their cognate
P2 receptors are emerging as key factors of inflammation and related
chemotactic responses. In this study, we investigated the activity
of extracellular adenosine triphosphate (ATP) and uridine triphosphate
(UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly
improved HSC migration, inhibited cell membrane CXCR4 down-regulation
by migrating CD34+ cells, and increased cell adhesion to fibronectin.
In vivo, preincubation with UTP significantly enhanced the BM homing
efficiency of human CD34+ cells in immunodeficient mice. Pertussis
toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting
that G-protein alpha-subunits (G{alpha}i) may provide a converging
signal for CXCR4- and P2Y-activated transduction pathways. In addition,
gene expression profiling of UTP- and CXCL12-treated CD34+ cells
and in vitro inhibition assays demonstrated that Rho guanosine 5'-triphosphatase
(GTPase) Rac2 and downstream effectors Rho GTPase-activated kinases
1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC
migration. Our data suggest that UTP may physiologically modulate
the homing of HSCs to the BM, in concert with CXCL12, via the activation
of converging signaling pathways between CXCR4 and P2Y receptors,
involving G{alpha}i proteins and RhoGTPases.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/2/533}
}
@ARTICLE{Rossi2005,
author = {Rossi, Marco and Sharkey, Andrew M and Vigano, Paola and Fiore, Giovina
and Furlong, Rob and Florio, Pasquale and Ambrosini, Guido and Smith,
Stephen K and Petraglia, Felice},
title = {Identification of genes regulated by interleukin-1{beta} in human
endometrial stromal cells},
journal = {Reproduction},
year = {2005},
volume = {130},
pages = {721--729},
number = {5},
month = nov,
abstract = {Interleukin-1{beta} (IL-1b) is an important immune regulatory factor
that in human endometrium plays a role in both menstruation and implantation
in the event of pregnancy. It promotes inflammatory-like processes
and also stimulates tissue remodelling. We present a cDNA microarray
study documenting the major effects of IL-1{beta} on gene expression
in stromal cells from human endometrium. Endometrial stromal cells
from five normal healthy women at the mid secretory phase were cultured
with or without IL-1{beta} at 50 and 500 pg/ml for 48 h. cDNA microarrays
were used to compare the levels of gene expression in total RNA isolated
from cells stimulated with IL-1{beta}. These cDNA arrays were produced
containing 15 164 sequence-verified clones, which included genes
known to be important in angiogenesis, immune modulators, apoptosis,
cell signalling, extra-cellular matrix (ECM) remodelling and cell
cycle regulation. Genes which were regulated by IL-1{beta} were identified
by analysis of the microarray data using the Significance Analysis
of Microarrays software package. Upregulated (n = 23) and downregulated
(n = 6) different genes were observed, which changed at least 3-fold,
at a false discovery rate of less than 2% (P < 0.02). Our results
have identified genes regulated by IL-1{beta}, which are involved
in leukocyte recruitment, ECM remodelling and other cellular functions.
Changes in three genes, IL-8, colony-stimulating factor 2 and aldoketo
reductase family 1 member 1, which were upregulated by IL-1{beta},
were verified using real-time PCR. Novel functions regulated by IL-1{beta}
in endometrium, including genes involved in free radical protection,
and fatty acid metabolism were also identified. These results also
provide new insights into the role of IL-1{beta} in disorders of
the endometrium, especially in implantation-related infertility and
endometriosis, in which this cytokine plays a major role.},
url = {http://www.reproduction-online.org/cgi/content/abstract/130/5/721}
}
@ARTICLE{Rossi2005a,
author = {Rossi, Michael R. and La Duca, Jeffrey and Matsui, Sei-Ichi and Nowak,
Norma J. and Hawthorn, Lesleyann and Cowell, John K.},
title = {Novel amplicons on the short arm of chromosome 7 identified using
high resolution array CGH contain over expressed genes in addition
to EGFR in glioblastoma multiforme},
journal = {Genes Chromosom. Cancer},
year = {2005},
volume = {44},
pages = {392--404},
number = {4},
abstract = {Abstract 10.1002/gcc.20256.abs Amplification of a defined chromosome
segment on the short arm of chromosome 7 has frequently been reported
in glioblastoma multiforme (GBM), where it is generally assumed that
it is the result of over expression of the epidermal growth factor
receptor (EGFR) gene that provides the selective pressure to maintain
the amplification event. We have used high resolution array comparative
genomic hybridization (aCGH) to analyze amplification events on chromosome
7p in GBM, which demonstrates that, in fact, several other regions
distinct from EGFR can be amplified. To determine the changes in
gene expression levels associated with these amplification events,
we used oligonucleotide expression arrays to investigate which of
the genes in the amplified regions were also over expressed. These
analyses demonstrated that not all genes in the amplicons showed
increased expression, and we have defined a series of over expressed
genes on 7p that could potentially contribute to the development
of the malignant phenotype in these tumors. The global analysis of
amplification afforded by aCGH analysis has improved our ability
to define numerical chromosome abnormalities in cancer cells and
has raised the possibility that genes other than EGFR may be important.
© 2005 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20256}
}
@ARTICLE{Rossier2008,
author = {Rossier, Joël S. and Baranek, Sophie and Morier, Patrick and Vollet,
Christine and Vulliet, François and De Chastonay, Yves and Reymond,
Frédéric},
title = {GRAVI: Robotized Microfluidics for Fast and Automated Immunoassays
in Low Volume},
journal = {Journal of the Association for Laboratory Automation},
year = {2008},
volume = {13},
pages = {322--329},
number = {6},
month = dec,
abstract = {GRAVI, presented here in its automated version, is a new bench-top
sized immunoassay platform combining the advantages of microfluidics
with those of simplified robotics. Characterized by dramatically
reduced time to result (<10 min) and significantly decreased sample/reagent
consumption, the cost-efficient biosensor instrumentation allows
performing multimenu analysis with minimal laboratory infrastructure.
Coupled to a robotic liquid handler, the system dispenses samples
and reagents from conventional plates or tubes into microchannels
of a microchip (GRAVI-Chip), in which assays are processed and results
readout. As in conventional 96-well microtiter plates, the microchannels
have a standard spacing of 9 mm to facilitate automation. With solely
gravity and capillary force-driven fluidics within the microchannels,
liquids are free to flow while magnetic beads, functionalized with
the antibody of choice, are trapped nearby incorporated electrodes
by virtue of a magnet array. Following assay performance and electrochemical
signal detection in the parallel microchannels, chips are regenerated
by magnet release and rinsing of beads out from the microchannels.
Applicability of the presented immunoassay platform, delivering 100
results per hour, is exemplified here with results from the validation
of an immunoglobulin assay for antibody quantification in mammalian
cell cultures. Adapted to run on the GRAVI platform, this competitive
assay covers a dynamic range of two orders of magnitude.},
issn = {1535-5535},
keywords = {microfluidics, microsensors, magnetic nanoparticles, immunoassay,
automation},
url = {http://www.sciencedirect.com/science/article/B75DF-4V0KV6H-9/2/c58ed733d677d2391db5132dfe40dec2}
}
@ARTICLE{Rossignol2009,
author = {Rossignol, Tristan and Ding, Chen and Guida, Alessandro and d'Enfert,
Christophe and Higgins, Desmond G. and Butler, Geraldine},
title = {Correlation between Biofilm Formation and the Hypoxic Response in
Candida parapsilosis},
journal = {Eukaryot. Cell},
year = {2009},
volume = {8},
pages = {550--559},
number = {4},
month = apr,
abstract = {The ability of Candida parapsilosis to form biofilms on indwelling
medical devices is correlated with virulence. To identify genes that
are important for biofilm formation, we used arrays representing
approximately 4,000 open reading frames (ORFs) to compare the transcriptional
profile of biofilm cells growing in a microfermentor under continuous
flow conditions with that of cells in planktonic culture. The expression
of genes involved in fatty acid and ergosterol metabolism and in
glycolysis, is upregulated in biofilms. The transcriptional profile
of C. parapsilosis biofilm cells resembles that of Candida albicans
cells grown under hypoxic conditions. We therefore subsequently used
whole-genome arrays (representing 5,900 ORFs) to determine the hypoxic
response of C. parapsilosis and showed that the levels of expression
of genes involved in the ergosterol and glycolytic pathways, together
with several cell wall genes, are increased. Our results indicate
that there is substantial overlap between the hypoxic responses of
C. parapsilosis and C. albicans and that this may be important for
biofilm development. Knocking out an ortholog of the cell wall gene
RBT1, whose expression is induced both in biofilms and under conditions
of hypoxia in C. parapsilosis, reduces biofilm development.},
url = {http://ec.asm.org/cgi/content/abstract/8/4/550}
}
@ARTICLE{Rossignol2011,
author = {Rossignol, Tristan and Kelly, Bridie and Dobson, Curtis and d'Enfert,
Christophe},
title = {Endocytosis-Mediated Vacuolar Accumulation of the Human ApoE Apolipoprotein-Derived
ApoEdpL-W Antimicrobial Peptide Contributes to Its Antifungal Activity
in Candida albicans},
journal = {Antimicrob. Agents Chemother.},
year = {2011},
volume = {55},
pages = {4670-4681},
number = {10},
abstract = {The 18-amino-acid cationic, tryptophan-rich ApoEdpL-W peptide derived
from human ApoE apolipoprotein was shown to have antifungal activity
against pathogenic yeasts of the Candida genus (except C. glabrata).
ApoEdpL-W was active against planktonic cells and early-stage biofilms
but less active against mature biofilms, possibly because of its
affinity for extracellular matrix beta-glucans. Moreover, ApoEdpL-W
absorbed to medically relevant materials partially prevented the
formation of biofilms on these materials. The exposure of C. albicans
cells to sublethal doses of ApoEdpL-W triggered a transcriptional
response reminiscent of that associated with the inactivation of
the MYO5 gene required for endocytosis as well as the upregulation
of amino acid transporter genes. A fluorescent derivative of ApoEdpL-W
accumulated at the cytoplasmic membrane and subsequently was translocated
to the vacuole. Strikingly, the inactivation of MYO5 or addition
of latrunculin, an inhibitor of endocytosis, prevented the vacuolar
accumulation of fluorescein-labeled ApoEdpL-W and reduced the antifungal
activity of ApoEdpL-W. This, together with the insensitivity of ApoEdpL-W
to alterations in membrane fluidity and high salt, suggested that
the ApoEdpL-W mode of action was dependent upon vacuolar targeting
and differed significantly from that of other antifungal peptides,
such as Histatin-5 and Magainin 2.},
doi = {10.1128/AAC.00319-11},
eprint = {http://aac.asm.org/cgi/reprint/55/10/4670.pdf},
url = {http://aac.asm.org/cgi/content/abstract/55/10/4670}
}
@ARTICLE{Rossignol2007,
author = {Rossignol, Tristan and Logue, Mary E. and Reynolds, Kieran and Grenon,
Muriel and Lowndes, Noel F. and Butler, Geraldine},
title = {Transcriptional Response of Candida parapsilosis following Exposure
to Farnesol},
journal = {Antimicrob. Agents Chemother.},
year = {2007},
volume = {51},
pages = {2304--2312},
number = {7},
month = jul,
abstract = {In Candida albicans, the quorum-sensing molecule farnesol inhibits
the transition from yeast to hyphae but has no effect on cellular
growth. We show that the addition of exogenous farnesol to cultures
of Candida parapsilosis causes the cells to arrest, but not at a
specific stage in the cell cycle. The cells are not susceptible to
additional farnesol. However, the cells do eventually recover from
arrest. Unlike in C. albicans, in C. parapsilosis sterols are localized
to the tips of budding cells, and this polarization is disrupted
by the addition of farnesol. We used the results of a genome sequence
survey to design and manufacture partial genomic microarrays that
were applied to determining the transcriptional response of C. parapsilosis
to the presence of exogenous farnesol. In both C. albicans and C.
parapsilosis, exposure to farnesol results in increased expression
of the oxidoreductases GRP2 and ADH7 and altered expression of genes
involved in sterol metabolism. There is no effect on expression of
C. parapsilosis orthologs of genes involved in hyphal growth in C.
albicans. Farnesol therefore differs significantly in its effects
on C. parapsilosis and C. albicans.},
url = {http://aac.asm.org/cgi/content/abstract/51/7/2304}
}
@ARTICLE{Rossler2001,
author = {Rossler, Oliver G. and Straka, Andreas and Stahl, Hans},
title = {Rearrangement of structured RNA via branch migration structures catalysed
by the highly related DEAD-box proteins p68 and p72},
journal = {Nucleic Acids Res.},
year = {2001},
volume = {29},
pages = {2088--2096},
number = {10},
month = may,
abstract = {RNA helicases, like their DNA-specific counterparts, can function
as processive enzymes, unwinding RNA with a defined step size in
a unidirectional fashion. Recombinant nuclear DEAD-box protein p68
and its close relative p72 are reported here to function in a similar
fashion, though the processivity of both RNA helicases appears to
be limited to only a few consecutive catalytic steps. The two proteins
resemble each other also with regard to other biochemical properties.
We have found that both proteins exhibit an RNA annealing in addition
to their helicase activity. By using both these activities the enzymes
are able in vitro to catalyse rearrangements of RNA secondary structures
that otherwise are too stable to be resolved by their low processive
helicase activities. RNA rearrangement proceeds via protein induced
formation and subsequent resolution of RNA branch migration structures,
whereby the latter step is dependent on ATP hydrolysis. The analysed
DEAD-box proteins are reminiscent of certain DNA helicases, for example
those found in bacteriophages T4 and T7, that catalyse homologous
DNA strand exchange in cooperation with the annealing activity of
specific single strand binding proteins.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/29/10/2088}
}
@ARTICLE{Rossner2006,
author = {Rossner, Moritz J. and Hirrlinger, Johannes and Wichert, Sven P.
and Boehm, Christine and Newrzella, Dieter and Hiemisch, Holger and
Eisenhardt, Gisela and Stuenkel, Carolin and von Ahsen, Oliver and
Nave, Klaus-Armin},
title = {Global Transcriptome Analysis of Genetically Identified Neurons in
the Adult Cortex},
journal = {J. Neurosci.},
year = {2006},
volume = {26},
pages = {9956--9966},
number = {39},
month = sep,
abstract = {The enormous cellular complexity of the brain is a major obstacle
for gene expression profiling of neurological disease models, because
physiologically relevant changes of transcription in a specific neuronal
subset are likely to be lost in the presence of other neurons and
glia. We solved this problem in transgenic mice by labeling genetically
defined cells with a nuclear variant of GFP. When combined with laser-directed
microdissection, intact RNA from unfixed, freeze-dried sections can
be isolated, which is a prerequisite for high-quality global transcriptome
analysis. Here, we compared gene expression profiles between pyramidal
motor neurons and pyramidal somatosensory neurons captured from layer
V of the adult neocortex. One striking feature of motor neurons is
the elevated expression of ribosomal genes and genes involved in
ATP synthesis. This suggests a molecular adaptation of the upper
motor neurons to longer axonal projections and higher electrical
activity. These molecular signatures were not detected when cortical
layers and microareas were analyzed in toto. Additionally, we used
microarrays to determine the global mRNA expression profiles of microdissected
Purkinje cells and cellularly complex cerebellar cortex microregions.
In summary, our analysis shows that cellularly complex targets lead
to averaged gene expression profiles that lack substantial amounts
of cell type-specific information. Thus, cell type-restricted sampling
strategies are mandatory in the CNS. The combined use of a genetic
label with laser-microdissection offers an unbiased approach to map
patterns of gene expression onto practically any cell type of the
brain.},
url = {http://www.jneurosci.org/cgi/content/abstract/26/39/9956}
}
@ARTICLE{Rosso2008,
author = {Rosso, Marie-Laure and Chauvaux, Sylvie and Dessein, Rodrigue and
Laurans, Caroline and Frangeul, Lionel and Lacroix, Céline and Schiavo,
Angèle and Dillies, Marie-Agnès and Foulon, Jeannine and Coppée,
Jean-Yves and Médigue, Claudine and Carniel, Elisabeth and Simonet,
Michel and Marceau, Michaël},
title = {Growth of Yersinia pseudotuberculosis in human plasma: impacts on
virulence and metabolic gene expression},
journal = {BMC Microbiology},
year = {2008},
volume = {8},
pages = {211},
number = {1},
abstract = {BACKGROUND:In man, infection by the Gram-negative enteropathogen Yersinia
pseudotuberculosis is usually limited to the terminal ileum. However,
in immunocompromised patients, the microorganism may disseminate
from the digestive tract and thus cause a systemic infection with
septicemia.RESULTS:To gain insight into the metabolic pathways and
virulence factors expressed by the bacterium at the blood stage of
pseudotuberculosis, we compared the overall gene transcription patterns
(the transcriptome) of bacterial cells cultured in either human plasma
or Luria-Bertani medium. The most marked plasma-triggered metabolic
consequence in Y. pseudotuberculosis was the switch to high glucose
consumption, which is reminiscent of the acetogenic pathway (known
as "glucose overflow") in Escherichia coli. However, upregulation
of the glyoxylate shunt enzymes suggests that (in contrast to E.
coli) acetate may be further metabolized in Y. pseudotuberculosis.
Our data also indicate that the bloodstream environment can regulate
major virulence genes (positively or negatively); the yadA adhesin
gene and most of the transcriptional units of the pYV-encoded type
III secretion apparatus were found to be upregulated, whereas transcription
of the pH6 antigen locus was strongly repressed.CONCLUSION:Our results
suggest that plasma growth of Y. pseudotuberculosis is responsible
for major transcriptional regulatory events and prompts key metabolic
reorientations within the bacterium, which may in turn have an impact
on virulence.},
doi = {10.1186/1471-2180-8-211},
issn = {1471-2180},
pubmedid = {19055764},
url = {http://www.biomedcentral.com/1471-2180/8/211}
}
@ARTICLE{Rossol-Allison2009,
author = {Rossol-Allison, Jessica and Stemmle, Laura N. and Swenson-Fields,
Katherine I. and Kelly, Patrick and Fields, Patrick E. and McCall,
Shannon J. and Casey, Patrick J. and Fields, Timothy A.},
title = {Rho GTPase activity modulates Wnt3a/[beta]-catenin signaling},
journal = {Cellular Signalling},
year = {2009},
volume = {21},
pages = {1559--1568},
number = {11},
month = nov,
abstract = {Wnt proteins constitute a family of secreted signaling molecules that
regulate highly conserved pathways essential for development and,
when aberrantly activated, drive oncogenesis in a number of human
cancers. A key feature of the most widely studied Wnt signaling cascade
is the stabilization of cytosolic [beta]-catenin, resulting in [beta]-catenin
nuclear translocation and transcriptional activation of multiple
target genes. In addition to this canonical, [beta]-catenin-dependent
pathway, Wnt3A has also been shown to stimulate RhoA GTPase. While
the importance of activated Rho to non-canonical Wnt signaling is
well appreciated, the potential contribution of Wnt3A-stimulated
RhoA to canonical [beta]-catenin-dependent transcription has not
been examined and is the focus of this study. We find that activated
Rho is required for Wnt3A-stimulated osteoblastic differentiation
in C3H10T1/2 mesenchymal stem cells, a biological phenomenon mediated
by stabilized [beta]-catenin. Using expression microarrays and real-time
RT-PCR analysis, we show that Wnt3A-stimulated transcription of a
subset of target genes is Rho-dependent, indicating that full induction
of these Wnt targets requires both [beta]-catenin and Rho activation.
Significantly, neither [beta]-catenin stabilization nor nuclear translocation
stimulated by Wnt3A is affected by inhibition or activation of RhoA.
These findings identify Rho activation as a critical element of the
canonical Wnt3A-stimulated, [beta]-catenin-dependent transcriptional
program.},
issn = {0898-6568},
keywords = {Wnt, RhoA, [beta]-catenin, RhoGTPase, Ctgf, Mesenchymal stem cell},
url = {http://www.sciencedirect.com/science/article/B6T2M-4WD7B6C-1/2/44d9fa71267cbf8e2f484e594b23e8e4}
}
@ARTICLE{Rossouw2008,
author = {Rossouw, Debra and Næs, Tormod and Bauer, Florian},
title = {Linking gene regulation and the exo-metabolome: A comparative transcriptomics
approach to identify genes that impact on the production of volatile
aroma compounds in yeast},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {530},
number = {1},
abstract = {BACKGROUND:'Omics' tools provide novel opportunities for system-wide
analysis of complex cellular functions. Secondary metabolism is an
example of a complex network of biochemical pathways, which, although
well mapped from a biochemical point of view, is not well understood
with regards to its physiological roles and genetic and biochemical
regulation. Many of the metabolites produced by this network such
as higher alcohols and esters are significant aroma impact compounds
in fermentation products, and different yeast strains are known to
produce highly divergent aroma profiles. Here, we investigated whether
we can predict the impact of specific genes of known or unknown function
on this metabolic network by combining whole transcriptome and partial
exo-metabolome analysis.RESULTS:For this purpose, the gene expression
levels of five different industrial wine yeast strains that produce
divergent aroma profiles were established at three different time
points of alcoholic fermentation in synthetic wine must. A matrix
of gene expression data was generated and integrated with the concentrations
of volatile aroma compounds measured at the same time points. This
relatively unbiased approach to the study of volatile aroma compounds
enabled us to identify candidate genes for aroma profile modification.
Five of these genes, namely YMR210W, BAT1, AAD10, AAD14 and ACS1
were selected for overexpression in commercial wine yeast, VIN13.
Analysis of the data show a statistically significant correlation
between the changes in the exo-metabome of the overexpressing strains
and the changes that were predicted based on the unbiased alignment
of transcriptomic and exo-metabolomic data.CONCLUSION:The data suggest
that a comparative transcriptomics and metabolomics approach can
be used to identify the metabolic impacts of the expression of individual
genes in complex systems, and the amenability of transcriptomic data
to direct applications of biotechnological relevance.},
doi = {10.1186/1471-2164-9-530},
issn = {1471-2164},
pubmedid = {18990252},
url = {http://www.biomedcentral.com/1471-2164/9/530}
}
@ARTICLE{Rossouw2009,
author = {Rossouw, Debra and Olivares-Hernandes, Roberto and Nielsen, Jens
and Bauer, Florian F.},
title = {Comparative Transcriptomic Approach To Investigate Differences in
Wine Yeast Physiology and Metabolism during Fermentation},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {6600--6612},
number = {20},
month = oct,
abstract = {Commercial wine yeast strains of the species Saccharomyces cerevisiae
have been selected to satisfy many different, and sometimes highly
specific, oenological requirements. As a consequence, more than 200
different strains with significantly diverging phenotypic traits
are produced globally. This genetic resource has been rather neglected
by the scientific community because industrial strains are less easily
manipulated than the limited number of laboratory strains that have
been successfully employed to investigate fundamental aspects of
cellular biology. However, laboratory strains are unsuitable for
the study of many phenotypes that are of significant scientific and
industrial interest. Here, we investigate whether a comparative transcriptomics
and phenomics approach, based on the analysis of five phenotypically
diverging industrial wine yeast strains, can provide insights into
the molecular networks that are responsible for the expression of
such phenotypes. For this purpose, some oenologically relevant phenotypes,
including resistance to various stresses, cell wall properties, and
metabolite production of these strains were evaluated and aligned
with transcriptomic data collected during alcoholic fermentation.
The data reveal significant differences in gene regulation between
the five strains. While the genetic complexity underlying the various
successive stress responses in a dynamic system such as wine fermentation
reveals the limits of the approach, many of the relevant differences
in gene expression can be linked to specific phenotypic differences
between the strains. This is, in particular, the case for many aspects
of metabolic regulation. The comparative approach therefore opens
new possibilities to investigate complex phenotypic traits on a molecular
level.},
url = {http://aem.asm.org/cgi/content/abstract/75/20/6600}
}
@ARTICLE{Rossouw2012,
author = {Debra Rossouw and Maret Du Toit and Florian F. Bauer},
title = {The impact of co-inoculation with Oenococcus oeni on the trancriptome
of Saccharomyces cerevisiae and on the flavour-active metabolite
profiles during fermentation in synthetic must},
journal = {Food Microbiology},
year = {2012},
volume = {29},
pages = {121 - 131},
number = {1},
abstract = {Co-inoculation of commercial yeast strains with a bacterial starter
culture at the beginning of fermentation of certain varietal grape
juices is rapidly becoming a preferred option in the global wine
industry, and frequently replaces the previously dominant sequential
inoculation strategy where bacterial strains, responsible for malolactic
fermentation, are inoculated after alcoholic fermentation has been
completed. However, while several studies have highlighted potential
advantages of co-inoculation, such studies have mainly focused on
broad fermentation properties of the mixed cultures, and no data
exist regarding the impact of this strategy on many oenologically
relevant attributes of specific wine yeast strains such as aroma
production. Here we investigate the impact of co-inoculation on a
commercial yeast strain during alcoholic fermentation by comparing
the transcriptome of this strain in yeast-only and in co-inoculated
fermentations of synthetic must. The data show that a significant
number of genes are differentially expressed in this strain in these
two conditions. Some of the differentially expressed genes appear
to respond to chemical changes in the fermenting must that are linked
to bacterial metabolic activities, whereas others might represent
a direct response of the yeast to the presence of a competing organism.},
doi = {10.1016/j.fm.2011.09.006},
issn = {0740-0020},
keywords = {Transcriptome},
url = {http://www.sciencedirect.com/science/article/pii/S0740002011002267}
}
@ARTICLE{Rostagno2010,
author = {Rostagno, Philippe and Wolchinsky, Zohar and Vigano, Alessandra M.
and Shivtiel, Shoham and Zhou, Huiqing and Van Bokhoven, Hans and
Ferone, Giustina and Missero, Caterina and Mantovani, Roberto and
Aberdam, Daniel and Virolle, Thierry},
title = {Embryonic stem cells as an ectodermal cellular model of human p63-related
dysplasia syndromes},
journal = {Biochemical and Biophysical Research Communications},
year = {2010},
volume = {395},
pages = {131--135},
number = {1},
month = apr,
abstract = {Heterozygous mutations in the TP63 transcription factor underlie the
molecular basis of several similar autosomal dominant ectodermal
dysplasia (ED) syndromes. Here we provide a novel cellular model
derived from embryonic stem (ES) cells that recapitulates in vitro
the main steps of embryonic skin development. We show that ES cells
carrying AEC or EEC mutations are unable to differentiate into the
epidermal fate. Comparative transcriptome analysis strongly reveals
an embryonic epidermal signature and suggests that mutations in the
SAM domain (AEC) provide activating properties while mutations in
the DBD domain (EEC) induce strong inhibitory capabilities. Our model
uncovers the effect of relevant ED mutations that otherwise are difficult
to evaluate on the ectodermal embryonic stage, an embryonic event
critical for proper skin formation.},
issn = {0006-291X},
keywords = {p63, Embryonic stem cells, Ectodermal dysplasia, Epidermal fate},
url = {http://www.sciencedirect.com/science/article/B6WBK-4YR8RBD-1/2/8e4ccb7c2956920153f9bf102b357ee6}
}
@ARTICLE{Rosti2006,
author = {Rosti, Sandrine and Rudi, Heidi and Rudi, Knut and Opsahl-Sorteberg,
Hilde-Gunn and Fahy, Brendan and Denyer, Kay},
title = {The gene encoding the cytosolic small subunit of ADP-glucose pyrophosphorylase
in barley endosperm also encodes the major plastidial small subunit
in the leaves},
journal = {J. Exp. Bot.},
year = {2006},
volume = {57},
pages = {3619--3626},
number = {14},
month = nov,
abstract = {The barley (Hordeum vulgare) gene Hv.AGP.S.1 produces two different
transcripts encoding small subunits (SSUs) of ADP-glucose pyrophosphorylase
(AGPase). It was shown previously that one of these transcripts,
Hv.1a, encodes the cytosolic SSU in the endosperm. It is shown here
that the other transcript produced from Hv.AGP.S.1, Hv.1b, encodes
a plastidial SSU that is required for >90% of the AGPase activity
in the leaves. Thus, both of the alternative transcripts encoded
by Hv.AGP.S.1 are physiologically relevant: One is important for
starch synthesis in the endosperm and the other for starch synthesis
in the leaves. Although the Hv.1b transcript is abundant in embryos
and present in endosperm, there is no evidence that a protein is
produced from this transcript in these organs. This suggests that
some, as yet unidentified, post-transcriptional control mechanism
prevents the accumulation of the protein encoded by Hv.1b in embryos
and endosperm but not in leaves. There is one other known gene in
barley, Hv.AGP.S.2, encoding a SSU of AGPase. This gene has been
shown to be responsible for the plastidial SSU in the endosperm.
It is shown here that Hv.AGP.S.2 probably also makes some contribution
to the SSU of AGPase in the leaves and may be responsible for most
or all of the plastidial SSU in a range of non-photosynthetic plant
organs including the embryo.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/57/14/3619}
}
@ARTICLE{Roth2011,
author = {Roth, Adrian and Boess, Franziska and Landes, Christian and Steiner,
Guido and Freichel, Christian and Plancher, Jean-Marc and Raab, Susanne
and de Vera Mudry, Cristina and Weiser, Thomas and Suter, Laura},
title = {Gene expression-based in vivo and in vitro prediction of liver toxicity
allows compound selection at an early stage of drug development},
journal = {Journal of Biochemical and Molecular Toxicology},
year = {2011},
volume = {25},
pages = {183--194},
number = {3},
abstract = {We have analyzed gene expression and histopathology of rat liver treated
with a histamine-3 receptor inverse agonist under development for
the treatment of obesity 24 h after a single acute administration.
While histopathology did not identify a clear liver toxicity, analysis
of gene changes strongly suggested the development of toxicity. This
prediction was confirmed in a 2-week repeat-dose rat study where
prominent liver pathology occurred, while gene changes that lead
to the prediction persisted. A subset of these genes was analyzed
in vitro in both rat and human hepatocytes to reveal the potential
relevancy of the findings for the situation in humans. This comprehensive
analysis of the development compound at the gene expression level
allowed interpretation of findings of the follow-up compound in a
frontloaded 24-h single-dose acute study that was initiated before
regular 2-week repeat-dose studies started. The high similarity of
the follow-up compound to the lead compound based on gene expression
lead to the immediate termination of the development program for
this compound series. Our data demonstrate the value of genomics-based
early toxicity prediction in short-term in vivo studies for the characterization
of compounds to allow prioritization and selection of suited candidates
before compound-, animal-, and cost-intensive longer term studies
are undertaken. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol
25:183–194, 2011; View this article online at wileyonlinelibrary.com.
DOI 10.1002/jbt.20375},
doi = {10.1002/jbt.20375},
issn = {1099-0461},
keywords = {Gene Expression, Hepatotoxicity, Hepatocytes, Prediction, Pathway},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jbt.20375}
}
@BOOK{Roth2005,
title = {ELECTROPHORESIS | Nucleic Acids},
publisher = {Elsevier},
year = {2005},
editor = {Worsfold, Paul and Townshend, Alan and Poole, Colin},
author = {Roth, C. M.},
pages = {456--460},
address = {Oxford},
booktitle = {Encyclopedia of Analytical Science},
issn = {978-0-12-369397-6},
url = {http://www.sciencedirect.com/science/article/B7GGK-4G7W8P5-2W/2/291fc05785ca646ecbcaedbcedf92d63}
}
@ARTICLE{Roth2009,
author = {Roth, Mark J. and Wei, Wen-Qiang and Baer, Jessica and Abnet, Christian
C. and Wang, Guo-Qing and Sternberg, Lawrence R. and Warner, Andrew
C. and Johnson, Laura Lee and Lu, Ning and Giffen, Carol A. and Dawsey,
Sanford M. and Qiao, You-Lin and Cherry, James},
title = {Aryl Hydrocarbon Receptor Expression Is Associated with a Family
History of Upper Gastrointestinal Tract Cancer in a High-Risk Population
Exposed to Aromatic Hydrocarbons},
journal = {Cancer Epidemiol. Biomarkers Prev.},
year = {2009},
volume = {18},
pages = {2391--2396},
number = {9},
month = sep,
abstract = {Background: Polycyclic aromatic hydrocarbon (PAH) exposure is a risk
factor for esophageal squamous cell carcinoma, and PAHs are ligands
of the aryl hydrocarbon receptor (AhR). This study measured the expression
of AhR and related genes in frozen esophageal cell samples from patients
exposed to different levels of indoor air pollution, who did or did
not have high-grade squamous dysplasia and who did or did not have
a family history of upper gastrointestinal tract (UGI) cancer. Methods:
147 samples were evaluated, including 23 (16%) from patients with
high-grade dysplasia and 48 (33%) from patients without dysplasia
who heated their homes with coal, without a chimney (a "high" indoor
air pollution group), and 27 (18%) from patients with high-grade
dysplasia and 49 (33%) from patients without dysplasia who did not
heat their homes at all (a "low" indoor air pollution group). Sixty-four
(44%) had a family history of UGI cancer. RNA was extracted and quantitative
PCR analysis was done. Results: AhR gene expression was detectable
in 85 (58%) of the samples and was >9-fold higher in those with a
family history of UGI cancer [median expression (interquartile range),
-1,964 (-18,000, -610) versus -18,000 (-18,000, -1036); P = 0.02,
Wilcoxon rank-sum test]. Heating status, dysplasia category, age,
gender, and smoking were not associated with AhR expression (linear
regression; all P values [≥] 0.1). Conclusion: AhR expression
was higher in patients with a family history of UGI cancer. Such
individuals may be more susceptible to the deleterious effects of
PAH exposure, including PAH-induced cancer. (Cancer Epidemiol Biomarkers
Prev 2009;18(9):2391-6)},
url = {http://cebp.aacrjournals.org/cgi/content/abstract/18/9/2391}
}
@ARTICLE{Rothem2011,
author = {Rothem, David E. and Rothem, Lilah and Dahan, Aviva and Eliakim,
Rami and Soudry, Michael},
title = {Nicotinic modulation of gene expression in osteoblast cells, MG-63},
journal = {Bone},
year = {2011},
volume = {48},
pages = {903--909},
number = {4},
month = apr,
abstract = {Exposure to nicotine causes a broad range of biological and molecular
effects on osteoblasts which are known to play a crucial role in
bone metabolism and fracture healing. Most effects of nicotine on
the osteoblasts are long-term adaptations at the genomic level. To
identify the nicotine-regulated genes, the Agilent technologies whole
human genome gene expression microarray was performed on RNA samples
from osteoblast-like cells, MG-63, exposed to 100 [mu]M nicotine.
Repeat and cross-controlled microarray analyses revealed 842 genes
whose expression was consistently altered at P < 0.05 level following
nicotine treatment. Gene ontology analysis suggested effects of nicotine
on various biological and cellular processes which were associated
with survival, proliferation, differentiation and apoptosis processes
within the cell. Quantitative real-time reverse transcriptase PCR
analysis confirmed altered expression in 7 out of 9 genes tested.
The identified genes tested in the current study support our previous
report that nicotine regulates the expression of genes that promote
osteoblast proliferation and/or anti-apoptosis processes. Furthermore,
using nicotinic acetylcholine receptor antagonists blocked the majority
of the nicotine effects, indicating that these changes are dependent
on nAChR activation. These results established a novel and consistent
nicotinic activation of nAChR in osteoblast cells which has a broad
role affecting cellular physiology through modulation of gene expression.},
issn = {8756-3282},
keywords = {Osteoblast, Nicotine, nAChR, Microarray, Gene expression, nAChR antagonists},
url = {http://www.sciencedirect.com/science/article/pii/S8756328210020934}
}
@ARTICLE{Rothgiesser2010,
author = {Rothgiesser, Karin and Fey, Monika and Hottiger, Michael},
title = {Acetylation of p65 at lysine 314 is important for late NF-?B-dependent
gene expression},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {22},
number = {1},
abstract = {BACKGROUND:NF-?B regulates the expression of a large number of target
genes involved in the immune and inflammatory response, apoptosis,
cell proliferation, differentiation and survival. We have earlier
reported that p65, a subunit of NF-?B, is acetylated in vitro and
in vivo at three different lysines (K310, K314 and K315) by the histone
acetyltransferase p300.RESULTS:In this study, we describe that site-specific
mutation of p65 at lysines 314 and 315 enhances gene expression of
a subset of NF-?B target genes including Mmp10 and Mmp13. Increased
gene expression was mainly observed three hours after TNFa stimulation.
Chromatin immunoprecipitation (ChIP) experiments with an antibody
raised against acetylated lysine 314 revealed that chromatin-bound
p65 is indeed acetylated at lysine 314.CONCLUSIONS:Together, our
results establish acetylation of K314 as an important regulatory
modification of p65 and subsequently of NF-?B-dependent gene expression.},
doi = {10.1186/1471-2164-11-22},
issn = {1471-2164},
pubmedid = {20064247},
url = {http://www.biomedcentral.com/1471-2164/11/22}
}
@ARTICLE{Rottscheidt2007,
author = {Rottscheidt, Ruth and Harr, Bettina},
title = {Extensive Additivity of Gene Expression Differentiates Subspecies
of the House Mouse},
journal = {Genetics},
year = {2007},
volume = {177},
pages = {1553--1567},
number = {3},
month = nov,
abstract = {We have studied different subspecies of the house mouse and their
reciprocal F1 hybrids to estimate the within-locus mode of inheritance
for subspecies differences in gene expression in three tissues (brain,
liver, and testis) of male mice. This study investigates the mode
of inheritance in crosses at a larger taxonomic distance than has
been previously systematically investigated. We found the vast majority
of transcripts to be additively expressed with only a few transcripts
showing dominance or overdominance in expression, except for one
direction of one cross, which showed large mis-expression in the
testis. We suggest that, as time passes, more genes come to influence
expression, and if there is no directional dominance, additivity
becomes increasingly more likely, up to a threshold beyond which
there is F1 hybrid breakdown. Some previous studies on different
organisms have found a large degree of dominance, commonly at shorter
taxonomic differences. We surveyed these findings and show that the
most consistent association exists between the amount of additivity
detected in a study and the expression analysis method (in particular
microarray platform), suggesting that at least some of the differences
among studies might be methodological. Most studies agree with ours
in that within-locus additivity seems to be general mode of inheritance
for transcript expression. Differentially expressed transcripts identified
in our screen among subspecies of house mice are candidate genes
that could be involved in reproductive isolation between these subspecies.},
url = {http://www.genetics.org/cgi/content/abstract/177/3/1553}
}
@ARTICLE{Rouleau2008,
author = {Rouleau, Cecile and Curiel, Maritza and Weber, William and Smale,
Robert and Kurtzberg, Leslie and Mascarello, James and Berger, Carol
and Wallar, Gina and Bagley, Rebecca and Honma, Nakayuki and Hasegawa,
Kazumasa and Ishida, Isao and Kataoka, Shiro and Thurberg, Beth L.
and Mehraein, Khodadad and Horten, Bruce and Miller, Glenn and Teicher,
Beverly A.},
title = {Endosialin Protein Expression and Therapeutic Target Potential in
Human Solid Tumors: Sarcoma versus Carcinoma},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {7223--7236},
number = {22},
month = nov,
abstract = {Purpose: Endosialin/CD248/tumor endothelial marker 1 is expressed
in stromal cells, endothelial cells, and pericytes in various tumors;
however, few studies have focused on expression in malignant cells.
Experimental Design: We studied expression of endosialin in clinical
specimens, cell culture, and animal models and designed an anti-endosialin
therapeutic prototype. Results: Fifty human tumor cell lines and
6 normal cell types in culture were assayed by reverse transcription-PCR
and/or flow cytometry for endosialin. Cell surface protein was found
on 7 sarcoma lines, 1 neuroblastoma, and 4 normal cell types in culture.
A fully human anti-endosialin antibody bound to human A-673 Ewing's
sarcoma cells and SK-N-AS neuroblastoma cells but not HT-1080 cells.
Exposure of cells to an anti-human IgG conjugated to saporin resulted
in growth inhibition only of endosialin-expressing cells. Endosialin
expression was assessed by immunohistochemistry in 250 clinical specimens
of human cancer including 20 cancer subtypes. Endosialin is frequently
found in human cancers. Endosialin expression is mainly a perivascular
feature in carcinomas, with some expression in stromal cells. In
sarcomas, endosialin is expressed by malignant cells, perivascular
cells, and stromal cells. Development and characterization of experimental
models for studying endosialin biology in sarcomas and evaluating
anti-endosialin therapies is presented. Conclusions: Findings suggest
that an anti-endosialin immunotoxin might be a promising therapeutic
approach for endosialin-positive neoplasia, especially synovial sarcoma,
fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, and osteosarcoma.
Thus, a diagnostic/therapeutic targeted therapeutic approach to treatment
of endosialin-expressing tumors may be possible.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/22/7223}
}
@ARTICLE{Rouquie2009,
author = {Rouquie, David and Friry-Santini, Claire and Schorsch, Frederic and
Tinwell, Helen and Bars, Remi},
title = {Standard and Molecular NOAELs for Rat Testicular Toxicity Induced
by Flutamide},
journal = {Toxicol. Sci.},
year = {2009},
volume = {109},
pages = {59--65},
number = {1},
month = may,
abstract = {An important step in the safety assessment of chemicals for humans
is to determine the no observed adverse effect level (NOAEL) in toxicity
studies conducted in animal models. With the increasing use of molecular
tools in toxicity studies, a question often posed is how a NOAEL
derived from molecular data compares to a NOAEL established using
standard methods. The objective of the present study was to address
this question when considering testicular toxicity. To do this, we
assessed the effects of the reference antiandrogen flutamide on rat
testes in a standard 28-day toxicity study using doses of 0.04-150
mg/kg/day. At necropsy, blood samples were collected for testosterone
measurements. The testes were collected for histopathological assessment
as well as for the evaluation of gene expression changes using quantitative
PCR analyses. Results showed that increases in plasma testosterone
level and Leydig cell hyperplasia were detected from 6 mg/kg/day.
An alteration in the level of accumulation of a selection of genes
was also detected from 6 mg/kg/day. This was the case for genes functionally
associated with the testicular lesion, such as lipid metabolism and
cell death/cell proliferation, as well as for genes not functionally
associated with the lesion. Contrary to the misgivings, these data
show that, using a standard 28-day toxicity study and a well-characterized
adverse effect, the NOAEL based on transcript changes is similar
to the NOAELs based on testosterone levels and histopathological
examination.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/109/1/59}
}
@ARTICLE{Rouse2008,
author = {Rouse, Rodney L. and Murphy, Gleeson and Boudreaux, Marc J. and Paulsen,
Daniel B. and Penn, Arthur L.},
title = {Soot Nanoparticles Promote Biotransformation, Oxidative Stress, and
Inflammation in Murine Lungs},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2008},
volume = {39},
pages = {198--207},
number = {2},
month = aug,
abstract = {We previously described the physicochemical characteristics (particle
size, adsorbed polynuclear aromatic hydrocarbons [PAHs], oxygen,
and metal content) of butadiene soot (BDS) nanoparticles generated
during incomplete combustion of the high-volume industrial petrochemical,
1,3-butadiene. We also demonstrated localization of BDS-delivered
PAHs to lipid droplets of murine and human respiratory cells in vitro
and up-regulation of biotransformation and oxidative stress responses
in these cells. Here, the objective was to determine whether inhalation
of BDS nanoparticles promotes up-regulation of Phase I biotransformation
enzymes, oxidative stress responses, and inflammation in the lungs
of mice. Female Balb/c mice exposed to BDS (5 mg/m3, 4 h/d, 4 d)
were killed immediately or 1 day after final exposure; bronchoalveolar
lavage fluid (BALF) was collected from the lungs; total RNA was extracted
from one lung and histopathology performed on the other. Histopathology
and BALF analysis revealed particle-laden macrophages in airways
of BDS-treated mice, accompanied by neutrophilia and epithelial damage.
Microarray and qRT-PCR analyses revealed up-regulation of (1) aryl
hydrocarbon receptor (AhR)-responsive genes: AhR repressor (Ahrr)
and cytochrome P450 IA1 and IB1(Cyp1a1, Cyp1b1); (2) oxidative stress
response genes: heme oxygenase 1 (Hmox1), nuclear factor erythroid-derived
2-like 2 (Nfe2l2), NADPH dehydrogenase quinone 1 (Nqo1), and glutathione
peroxidase 2 (Gpx2); and (3) pro-inflammatory genes: interleukin-6
(IL-6), C-X-C motif ligand 2 (Cxcl2; analog to human IL-8) and ligand
3 (Cxcl3), and granulocyte chemotactic protein (Cxcl6). Inhalation
of PAH-rich, petrochemical combustion-derived nanoparticles causes
airway inflammation and induces expression of AhR-associated and
oxidative stress response genes, as seen in vitro, plus pro-inflammatory
genes.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/39/2/198}
}
@ARTICLE{Rouse2011,
author = {Rouse, Rodney L and Zhang, Jun and Stewart, Sharron R and Rosenzweig,
Barry A and Espandiari, Parvaneh and Sadrieh, Nakissa K},
title = {Comparative profile of commercially available urinary biomarkers
in preclinical drug-induced kidney injury and recovery in rats},
journal = {Kidney Int},
year = {2011},
volume = {79},
pages = {1186--1197},
number = {11},
month = jun,
issn = {0085-2538},
publisher = {International Society of Nephrology},
url = {http://dx.doi.org/10.1038/ki.2010.463}
}
@ARTICLE{Rousseau2010,
author = {Rousseau, Justine and Klinger, Sonia and Rachalski, Adeline and Turgeon,
Benjamin and Deleris, Paul and Vigneault, Erika and Poirier-Heon,
Jean-Francois and Davoli, Maria Antonietta and Mechawar, Naguib and
El Mestikawy, Salah and Cermakian, Nicolas and Meloche, Sylvain},
title = {Targeted Inactivation of Mapk4 in Mice Reveals Specific Nonredundant
Functions of Erk3/Erk4 Subfamily Mitogen-Activated Protein Kinases},
journal = {Mol. Cell. Biol.},
year = {2010},
volume = {30},
pages = {5752--5763},
number = {24},
month = dec,
abstract = {Erk4 and Erk3 are atypical members of the mitogen-activated protein
(MAP) kinase family. The high sequence identity of Erk4 and Erk3
proteins and the similar organization of their genes imply that the
two protein kinases are paralogs. Recently, we have shown that Erk3
function is essential for neonatal survival and critical for the
establishment of fetal growth potential and pulmonary function. To
investigate the specific functions of Erk4, we have generated mice
with a targeted disruption of the Mapk4 gene. We show that Erk4-deficient
mice are viable and fertile and exhibit no gross morphological or
physiological anomalies. Loss of Erk4 is not compensated by changes
in Erk3 expression or activity during embryogenesis or in adult tissues.
We further demonstrate that additional loss of Erk4 does not exacerbate
the fetal growth restriction and pulmonary immaturity phenotypes
of Erk3-/- mice and does not compromise the viability of Erk3+/-
neonates. Interestingly, behavioral phenotyping revealed that Erk4-deficient
mice manifest depression-like behavior in the forced-swimming test.
Our analysis indicates that the MAP kinase Erk4 is dispensable for
mouse embryonic development and reveals that Erk3 and Erk4 have acquired
specialized functions through evolutionary diversification.},
comment = {10.1128/MCB.01147-10},
url = {http://mcb.asm.org/cgi/content/abstract/30/24/5752}
}
@ARTICLE{Rousset2011,
author = {Rousset, B. and Ziercher, L. and Borson-Chazot, F.},
title = {Molecular analyses of thyroid tumors for diagnosis of malignancy
on fine-needle aspiration biopsies and for prognosis of invasiveness
on surgical specimens},
journal = {Annales d'Endocrinologie},
year = {2011},
volume = {72},
pages = {125--128},
number = {2},
month = apr,
abstract = {High throughput genetic and genomic analyses have allowed the identification
of series of genes exhibiting either distinct expression profiles
or a particular mutational status in the different types or subtypes
of thyroid tumors. The use of molecular data to improve the preoperative
diagnosis of thyroid cancer on materiel from fine-needle aspiration
biopsy (FNAB) is in the course of validation by numerous teams throughout
the world. We have proposed a molecular test based on the expression
level of a series of 19 genes, capable of discriminating malignant
from benign tumors [15]. A prospective study aiming at the clinical
validation of the molecular test has been performed on a cohort of
730 patients with a thyroid nodule. In patients subjected to tumor
resection ([approximate] 220), the preoperative molecular diagnosis
(generated on FNAB material from analyses of the expression level
of the 19 genes) was compared to the postoperative diagnosis given
by the pathologist (used as reference). Treatment and follow-up of
the serious forms of thyroid cancer should benefit by the early identification
of tumors with a metastatic potential using molecular characteristics
differentiating invasive and non-invasive thyroid carcinomas. We
have performed genetic and genomic analyses on a series of 200 papillary
thyroid carcinomas (non-invasive or NI-PTC, 50%; invasive or I-PTC,
50%). BRAFV600E mutation or/and RET/PTC gene rearrangement have been
detected in less than 25% of NI-PTC but in more than 75% of I-PTC.
Pan-genomic analyses (Agilent microarray) revealed that 1373 genes
are differentially expressed (fold change greater than 2) in NI-PTC
as compared to I-PTC samples. The majority of genes ([approximate]
1200) are overexpressed in I-PTC. Data related to the two domains:
diagnosis and prognosis of thyroid cancer will be presented at 2011
International H.P. KLOTZ conference on Clinical Endocrinology.},
booktitle = {54es Journees internationales d'Endocrinologie clinique},
issn = {0003-4266},
keywords = {Cancer de la thyroïde, Cytoponction thyroïdienne, Diagnostic moléculaire,
Cancer invasif, Invasivité, Potentiel métastatique, Transcriptome
pan-génomique, Thyroid cancer, Fine-needle aspiration biopsy, Molecular
diagnosis, Papillary thyroid cancer, Invasiveness, Metastatic potential,
Pan-genomic transcript analyses},
url = {http://www.sciencedirect.com/science/article/pii/S0003426611000448}
}
@ARTICLE{Roux2011,
author = {Roux, Anne-Laure and Ray, Aurélie and Pawlik, Alexandre and Medjahed,
Halima and Etienne, Gilles and Rottman, Martin and Catherinot, Emilie
and Coppée, Jean-Yves and Chaoui, Karima and Monsarrat, Bernard
and Toubert, Antoine and Daffé, Mamadou and Puzo, Germain and Gaillard,
Jean-Louis and Brosch, Roland and Dulphy, Nicolas and Nigou, Jérôme
and Herrmann, Jean-Louis},
title = {Overexpression of proinflammatory TLR-2-signalling lipoproteins in
hypervirulent mycobacterial variants},
journal = {Cellular Microbiology},
year = {2011},
volume = {13},
pages = {692--704},
number = {5},
abstract = {Summary Changes in the cell envelope composition of mycobacteria cause
major changes in cytokine profiles of infected antigen presenting
cells. We describe here the modulation of inflammatory responses
by Mycobacterium abscessus, an emerging pathogen in cystic fibrosis.
M. abscessus is able to switch from a smooth (S) to a rough (R) morphotype
by the loss of a surface glycopeptidolipid. R variants are associated
with severe clinical forms and a ‘hyper-proinflammatory’ response
in ex vivo and in vivo models. Using partitioning of cell surface
components we found that a complex fraction, more abundant in R variants
than in S variants, made a major contribution to the TLR-2-dependent
hyper-proinflammatory response induced by R variants. Lipoproteins
were the main TLR-2 agonists in this fraction, consistent with the
larger amounts of 16 lipoproteins in cell surface extracts from R
variants; 15 out of 16 being more strongly induced in R variant than
in S variant. Genetic interruption of glycopeptidolipid pathway in
wild-type S variant resulted in R phenotype with similar induction
of lipoprotein genes. In conclusion, R morphotype in M. abscessus
is associated with increased synthesis/exposure at the cell surface
of lipoproteins, these changes profoundly modifying the innate immune
response through TLR-2-dependent mechanisms.},
doi = {10.1111/j.1462-5822.2010.01565.x},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2010.01565.x}
}
@ARTICLE{Roux2007,
author = {Roux, Christelle M. and Rolán, Hortensia G. and Santos, Renato L.
and Beremand, Phillip D. and Thomas, Terry L. and Adams, L. Garry
and Tsolis, Renée M.},
title = {Brucella requires a functional Type IV secretion system to elicit
innate immune responses in mice},
journal = {Cellular Microbiology},
year = {2007},
volume = {9},
pages = {1851--1869},
number = {7},
abstract = {Summary The virB operon, encoding a Type IV secretion system (T4SS),
is essential for intracellular survival and persistent infection
by Brucella spp. To better understand the role of the T4SS in evading
host defence mechanisms and establishing chronic infection, we compared
transcriptional profiles of the host response to infection with wild-type
and virB mutant Brucella strains. Analysis of gene expression profiles
in murine splenocytes 3Â days after inoculation with wild-type Brucella
strains revealed an inflammatory response, with a prominent upregulation
of genes induced by both type I and type II interferons. Real-time
RT-PCR showed that a group of genes from these pathways were induced
by day 3 post infection and declined to baseline levels by day 7.
In contrast, neither of the two virB mutant strains elicited a proinflammatory
gene expression profile, demonstrating that the T4SS was required
to trigger this response. Infection studies using type I interferon
receptor knockout mice showed that a lack of type I interferon signalling
did not affect Brucella replication during the first 4Â weeks of
infection. Thus, induction of type I interferons does not appear
to be an essential mechanism by which the T4SS promotes persistent
infection by Brucella.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2007.00922.x}
}
@ARTICLE{Roux2012,
author = {Jean-Christophe Roux and Diana Zala and Nicolas Panayotis and Ana
Borges-Correia and Frédéric Saudou and Laurent Villard},
title = {Modification of Mecp2 dosage alters axonal transport through the
Huntingtin/Hap1 pathway},
journal = {Neurobiology of Disease},
year = {2012},
volume = {45},
pages = {786 - 795},
number = {2},
abstract = {Mecp2 deficiency or overexpression causes a wide spectrum of neurological
diseases in humans among which Rett Syndrome is the prototype. Pathogenic
mechanisms are thought to involve transcriptional deregulation of
target genes such as Bdnf together with defects in the general transcriptional
program of affected cells. Here we found that two master genes, Huntingtin
(Htt) and huntingtin-associated protein (Hap1), involved in the control
of Bdnf axonal transport, are altered in the brain of Mecp2-deficient
mice. We also revealed an in vivo defect of Bdnf transport throughout
the cortico striatal pathway of Mecp2-deficient animals. We found
that the velocity of Bdnf-containing vesicles is reduced in vitro
in the Mecp2-deficient axons and this deficit can be rescued by the
re-expression of Mecp2. The defect in axonal transport is not restricted
to Bdnf since transport of the amyloid precursor protein (App) that
is Htt and Hap1-dependent is also altered. Finally, treating Mecp2-deficient
mice with cysteamine, a molecule increasing the secretion of Bdnf
vesicles, improved the lifespan and reduced motor defects, suggesting
a new therapeutic strategy for Rett syndrome.},
doi = {10.1016/j.nbd.2011.11.002},
issn = {0969-9961},
keywords = {Rett syndrome},
url = {http://www.sciencedirect.com/science/article/pii/S0969996111003718}
}
@ARTICLE{Rouzier2005,
author = {Rouzier, Roman and Perou, Charles M. and Symmans, W. Fraser and Ibrahim,
Nuhad and Cristofanilli, Massimo and Anderson, Keith and Hess, Kenneth
R. and Stec, James and Ayers, Mark and Wagner, Peter and Morandi,
Paolo and Fan, Chang and Rabiul, Islam and Ross, Jeffrey S. and Hortobagyi,
Gabriel N. and Pusztai, Lajos},
title = {Breast Cancer Molecular Subtypes Respond Differently to Preoperative
Chemotherapy},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {5678--5685},
number = {16},
month = aug,
abstract = {Purpose: Molecular classification of breast cancer has been proposed
based on gene expression profiles of human tumors. Luminal, basal-like,
normal-like, and erbB2+ subgroups were identified and were shown
to have different prognoses. The goal of this research was to determine
if these different molecular subtypes of breast cancer also respond
differently to preoperative chemotherapy. Experimental Design: Fine
needle aspirations of 82 breast cancers were obtained before starting
preoperative paclitaxel followed by 5-fluorouracil, doxorubicin,
and cyclophosphamide chemotherapy. Gene expression profiling was
done with Affymetrix U133A microarrays and the previously reported
"breast intrinsic" gene set was used for hierarchical clustering
and multidimensional scaling to assign molecular class. Results:
The basal-like and erbB2+ subgroups were associated with the highest
rates of pathologic complete response (CR), 45% [95% confidence interval
(95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the
luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No
pathologic CR was observed among the normal-like cancers (95% CI,
0-31). Molecular class was not independent of conventional cliniocopathologic
predictors of response such as estrogen receptor status and nuclear
grade. None of the 61 genes associated with pathologic CR in the
basal-like group were associated with pathologic CR in the erbB2+
group, suggesting that the molecular mechanisms of chemotherapy sensitivity
may vary between these two estrogen receptor-negative subtypes. Conclusions:
The basal-like and erbB2+ subtypes of breast cancer are more sensitive
to paclitaxel- and doxorubicin-containing preoperative chemotherapy
than the luminal and normal-like cancers.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/16/5678}
}
@ARTICLE{Rovery2005,
author = {Rovery, C And La, M V And Robineau, S And Matsumoto, K And Renesto,
P And Raoult, D},
title = {Preliminary Transcriptional Analysis of spoT Gene Family and of Membrane
Proteins in Rickettsia conorii and Rickettsia felis},
journal = {Annals of the New York Academy of Sciences},
year = {2005},
volume = {1063},
pages = {79--82},
number = {1},
abstract = {Abstract: Rickettsiae survival implicates adaptation to different
environmental conditions. We hypothesized that multiple copies of
genes in bacteria with reduced genomes might account for such a process.
Transcription of spoT and sca paralogs was thus analyzed in R. conorii
and R. felis.},
issn = {1749-6632},
keywords = {Rickettsia conorii, Rickettsia felis, transcriptome, spoT, sca},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1196/annals.1355.011}
}
@ARTICLE{Rovira-Vallbona2011,
author = {Rovira-Vallbona, Eduard and Dobano, Carlota and Bardaji, Azucena
and Cistero, Pau and Romagosa, Cleofe and Serra-Casas, Elisa and
Quinto, Llorenc and Bassat, Quique and Sigauque, Betuel and Alonso,
Pedro L. and Ordi, Jaume and Menendez, Clara and Mayor, Alfredo},
title = {Transcription of var Genes Other Than var2csa in Plasmodium falciparum
Parasites Infecting Mozambican Pregnant Women},
journal = {The Journal of Infectious Disease},
year = {2011},
volume = {204},
pages = {27-35},
number = {1},
abstract = {Background. Increased susceptibility to Plasmodium falciparum infection
during pregnancy has been attributed to the accumulation of infected
erythrocytes in the placenta. This phenomenon is mediated by a var
gene coding for VAR2CSA, which adheres to chondroitin sulphate A.
However, the contribution of parasites transcribing other var genes
to maternal infections has not been well characterized. Methods.
Transcription of var2csa and var groups A, B, and C was measured
by real-time polymerase chain reaction in 30 placental and 21 peripheral
P. falciparum isolates from pregnant women and in 42 isolates from
nonpregnant adults and children. Associations of infections with
non-var2csa isolates with maternal parasitemia and immune responses
were assessed. Results. Placental parasites showed the highest levels
of var2csa. ABC var genes were transcribed by 20 (67%) of 30 placental
isolates and were associated with higher parasitemia compared with
infections by parasites only transcribing var2csa (P = .004). Peripheral
isolates from pregnant women transcribed ABC var genes at levels
similar to those of parasites infecting nonpregnant adults with clinical
malaria (P[varA] = .420, P[varB] = .808, and P[varC] = .619). Conclusions.
Transcripts of var2csa are abundant in pregnancy-associated P. falciparum
infections; however, ABC var types are also common, especially in
peripheral blood, with transcription levels similar to those of infections
out of pregnancy. These findings are of interest for the design of
malaria vaccines for pregnant women.},
doi = {10.1093/infdis/jir217},
eprint = {http://jid.oxfordjournals.org//cgi/reprint/204/1/27.pdf},
url = {http://jid.oxfordjournals.org//cgi/content/abstract/204/1/27}
}
@ARTICLE{Rovsing2011,
author = {Rovsing, Louise and Clokie, Samuel and Bustos, Diego M. and Rohde,
Kristian and Coon, Steven L. and Litman, Thomas and Rath, Martin
F. and Møller, Morten and Klein, David C.},
title = {Crx broadly modulates the pineal transcriptome},
journal = {Journal of Neurochemistry},
year = {2011},
volume = {119},
pages = {262--274},
number = {2},
abstract = {J. Neurochem. (2011) 119, 262–274.AbstractCone-rod homeobox (Crx)
encodes Crx, a transcription factor expressed selectively in retinal
photoreceptors and pinealocytes, the major cell type of the pineal
gland. In this study, the influence of Crx on the mammalian pineal
gland was studied by light and electron microscopy and by use of
microarray and qRTPCR technology, thereby extending previous studies
on selected genes (Furukawa et al. 1999). Deletion of Crx was not
found to alter pineal morphology, but was found to broadly modulate
the mouse pineal transcriptome, characterized by a > 2-fold down-regulation
of 543 genes and a > 2-fold up-regulation of 745 genes (p < 0.05).
Of these, one of the most highly up-regulated (18-fold) was Hoxc4,
a member of the Hox gene family, members of which are known to control
gene expression cascades. During a 24-h period, a set of 51 genes
exhibited differential day/night expression in pineal glands of wild-type
animals; only eight of these were also day/night expressed in the
Crx−/− pineal gland. However, in the Crx−/− pineal gland
41 genes exhibited differential night/day expression that was not
seen in wild-type animals. These findings indicate that Crx broadly
modulates the pineal transcriptome and also influences differential
night/day gene expression in this tissue. Some effects of Crx deletion
on the pineal transcriptome might be mediated by Hoxc4 up-regulation.},
doi = {10.1111/j.1471-4159.2011.07405.x},
issn = {1471-4159},
keywords = {Crx, gene expression, Hoxc4, microarray, pineal gland, transcriptome
profiling},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07405.x}
}
@ARTICLE{Rowe2008,
author = {Rowe, A. and Gondro, C. and Emery, D. and Sangster, N.},
title = {Genomic analyses of Haemonchus contortus infection in sheep: Abomasal
fistulation and two Haemonchus strains do not substantially confound
host gene expression in microarrays},
journal = {Veterinary Parasitology},
year = {2008},
volume = {154},
pages = {71--81},
number = {1-2},
month = jun,
abstract = {To determine whether fistulation and differing strains of Haemonchus
contortus complicate genome analysis of the host response to infection,
two pilot experiments examined parasite development and gene expression
in the abomasal mucosa of parasitised sheep. No significant differentially-expressed
genes were detected in a comparison between ivermectin-susceptible
McMaster and ivermectin-resistant CAVR strains of H. contortus. This
demonstrated that the sheep response was not significantly altered
by the ivermectin-resistance status of the parasite. However, sheep
infected with McMaster strain had a significantly lower proportion
of larvae and a higher mean FEC at post-mortem than sheep infected
with CAVR, suggesting that McMaster larvae advance to patency faster
than CAVR larvae. Abomasal fistulation resulted in significant upregulation
of three genes and significant downregulation of two genes. Fistulated
sheep had significantly lower FEC than the other groups but the proportion
of larvae at post-mortem was not significantly different to other
groups infected with the same strain (CAVR). Hence fistulation does
not alter establishment of the CAVR isolate, but may slow its progression
to patency. The observation that different H. contortus strains and
abomasal fistulation induced minimal changes in mucosal gene expression
validated the design of a subsequent experiment (manuscript in preparation)
where sequential biopsies taken during infection were analysed by
microarray to describe the molecular responses which inhibit larval
establishment.},
issn = {0304-4017},
keywords = {Haemonchus contortus, Strain, Microarray, Abomasal fistula},
url = {http://www.sciencedirect.com/science/article/B6TD7-4RX077C-2/2/2d76a82f8191aa13b8bc0e6fd8ad8951}
}
@ARTICLE{Rowe2008a,
author = {Rowe, Annette R. and Lazar, Brendan J. and Morris, Robert M. and
Richardson, Ruth E.},
title = {Characterization of the Community Structure of a Dechlorinating Mixed
Culture and Comparisons of Gene Expression in Planktonic and Biofloc-Associated
"Dehalococcoides" and Methanospirillum Species},
journal = {Appl. Envir. Microbiol.},
year = {2008},
volume = {74},
pages = {6709--6719},
number = {21},
month = nov,
abstract = {This study sought to characterize bacterial and archaeal populations
in a perchloroethene- and butyrate-fed enrichment culture containing
hydrogen-consuming "Dehalococcoides ethenogenes" strain 195 and a
Methanospirillum hungatei strain. Phylogenetic characterization of
this microbial community was done via 16S rRNA gene clone library
and gradient gel electrophoresis analyses. Fluorescence in situ hybridization
was used to quantify populations of "Dehalococcoides" and Archaea
and to examine the colocalization of these two groups within culture
bioflocs. A technique for enrichment of planktonic and biofloc-associated
biomass was developed and used to assess differences in population
distribution and gene expression patterns following provision of
substrate. On a per-milliliter-of-culture basis, most D. ethenogenes
genes (the hydrogenase gene hupL; the highly expressed gene for an
oxidoreductase of unknown function, fdhA; the RNA polymerase subunit
gene rpoB; and the 16S rRNA gene) showed no statistical difference
in expression between planktonic and biofloc enrichments at either
time point studied (1 to 2 and 6 h postfeeding). Normalization of
transcripts to ribosome (16S rRNA) levels supported that planktonic
and biofloc-associated D. ethenogenes had similar gene expression
profiles, with one notable exception; planktonic D. ethenogenes showed
higher expression of tceA relative to biofloc-associated cells at
6 h postfeeding. These trends were compared to those for the hydrogen-consuming
methanogen in the culture, M. hungatei. The vast majority of M. hungatei
cells, ribosomes (16S rRNA), and transcripts of the hydrogenase gene
mvrD and the housekeeping gene rpoE were observed in the biofloc
enrichments. This suggests that, unlike the comparable activity of
D. ethenogenes from both enrichments, planktonic M. hungatei is responsible
for only a small fraction of the hydrogenotrophic methanogenesis
in this culture.},
url = {http://aem.asm.org/cgi/content/abstract/74/21/6709}
}
@ARTICLE{ROWE2011,
author = {ROWE, KEVIN C. and SINGHAL, SONAL and MACMANES, MATTHEW D. and AYROLES,
JULIEN F. and MORELLI, TONI LYN and RUBIDGE, EMILY M. and BI, KE
and MORITZ, CRAIG C.},
title = {Museum genomics: low-cost and high-accuracy genetic data from historical
specimens},
journal = {Molecular Ecology Resources},
year = {2011},
volume = {11},
pages = {1082--1092},
number = {6},
abstract = {Natural history collections are unparalleled repositories of geographical
and temporal variation in faunal conditions. Molecular studies offer
an opportunity to uncover much of this variation; however, genetic
studies of historical museum specimens typically rely on extracting
highly degraded and chemically modified DNA samples from skins, skulls
or other dried samples. Despite this limitation, obtaining short
fragments of DNA sequences using traditional PCR amplification of
DNA has been the primary method for genetic study of historical specimens.
Few laboratories have succeeded in obtaining genome-scale sequences
from historical specimens and then only with considerable effort
and cost. Here, we describe a low-cost approach using high-throughput
next-generation sequencing to obtain reliable genome-scale sequence
data from a traditionally preserved mammal skin and skull using a
simple extraction protocol. We show that single-nucleotide polymorphisms
(SNPs) from the genome sequences obtained independently from the
skin and from the skull are highly repeatable compared to a reference
genome.},
doi = {10.1111/j.1755-0998.2011.03052.x},
issn = {1755-0998},
keywords = {historical DNA, natural history collections, next-generation sequencing,
Rattus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-0998.2011.03052.x}
}
@ARTICLE{Rowe2007,
author = {Rowe, Wayne B. and Blalock, Eric M. and Chen, Kuey-Chu and Kadish,
Inga and Wang, Daguang and Barrett, James E. and Thibault, Olivier
and Porter, Nada M. and Rose, Gregory M. and Landfield, Philip W.},
title = {Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early,
Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment
in Aged Rats},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {3098--3110},
number = {12},
month = mar,
abstract = {Although expression of some genes is known to change during neuronal
activity or plasticity, the overall relationship of gene expression
changes to memory or memory disorders is not well understood. Here,
we combined extensive statistical microarray analyses with behavioral
testing to comprehensively identify genes and pathways associated
with aging and cognitive dysfunction. Aged rats were separated into
cognitively unimpaired (AU) or impaired (AI) groups based on their
Morris water maze performance relative to young-adult (Y) animals.
Hippocampal gene expression was assessed in Y, AU, and AI on the
fifth (last) day of maze training (5T) or 21 d posttraining (21PT)
and in nontrained animals (eight groups total, one array per animal;
n = 78 arrays). ANOVA and linear contrasts identified genes that
differed from Y generally with aging (differed in both AU and AI)
or selectively, with cognitive status (differed only in AI or AU).
Altered pathways/processes were identified by overrepresentation
analyses of changed genes. With general aging, there was downregulation
of axonal growth, cytoskeletal assembly/transport, signaling, and
lipogenic/uptake pathways, concomitant with upregulation in immune/inflammatory,
lysosomal, lipid/protein degradation, cholesterol transport, transforming
growth factor, and cAMP signaling pathways, primarily independent
of training condition. Selectively, in AI, there was downregulation
at 5T of immediate-early gene, Wnt (wingless integration site), insulin,
and G-protein signaling, lipogenesis, and glucose utilization pathways,
whereas Notch2 (oligodendrocyte development) and myelination pathways
were upregulated, particularly at 21PT. In AU, receptor/signal transduction
genes were upregulated, perhaps as compensatory responses. Immunohistochemistry
confirmed and extended selected microarray results. Together, the
findings suggest a new model, in which deficient neuroenergetics
leads to downregulated neuronal signaling and increased glial activation,
resulting in aging-related cognitive dysfunction.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/12/3098}
}
@ARTICLE{Rowlands2011,
author = {J. Craig Rowlands and Robert Budinsky and Bhaskar Gollapudi and Raymond
Novak and Mohamed Abdelmegeed and Daniela Cukovic and Alan Dombkowski},
title = {Transcriptional profiles induced by the Aryl Hydrocarbon Receptor
agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran
and 2,3,4,7,8-pentachlorodibenzofuran in primary rat hepatocytes},
journal = {Chemosphere},
year = {2011},
volume = {85},
pages = {232 - 238},
number = {2},
note = {Special Issue in Honour and Remembrance of Dr. Larry Needham’},
abstract = {Toxicogenomics was used to examine mRNA expression profiles obtained
from primary rat hepatocytes treated for 24 h with 0.01 or 1.0 nM
2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), 0.02 or 2.0 nM
2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and 0.1 or 10 nM
2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF). The concentrations
of 2,3,4,7,8-PeCDF and 2,3,7,8-TCDF were chosen to be equivalent
to 2,3,7,8-TCDD’s concentration based on the toxic equivalency
factor/toxic equivalent (TEF/TEQ) method for estimating biological
potency. 2,3,7,8-TCDD at 1.0 nM altered the expression of 533
genes; 2,3,4,7,8-PeCDF at 2.0 nM altered 182 genes, and 2,3,7,8-TCDF
at 10 nM altered 154 genes. Of these, 57 genes were affected
by all three congeners. Agglomerative hierarchical clustering revealed
distinct congener-dependent gene subclusters. Principal components
analyses of the microarray data revealed that these congeners cluster
independently of one another. Data presented here demonstrate that
equivalent TEQ concentrations of 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF and
2,3,7,8-TCDF, while altering the expression of a small battery of
genes in common, also produce substantial congener specific alterations
in gene expression.},
doi = {10.1016/j.chemosphere.2011.06.026},
issn = {0045-6535},
keywords = {Genomics},
url = {http://www.sciencedirect.com/science/article/pii/S0045653511006692}
}
@ARTICLE{Rowley2011,
author = {Rowley, Jesse W. and Oler, Andrew J. and Tolley, Neal D. and Hunter,
Benjamin N. and Low, Elizabeth N. and Nix, David A. and Yost, Christian
C. and Zimmerman, Guy A. and Weyrich, Andrew S.},
title = {Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes},
journal = {Blood},
year = {2011},
volume = {118},
pages = {e101-111},
number = {14},
abstract = {Inbred mice are a useful tool for studying the in vivo functions of
platelets. Nonetheless, the mRNA signature of mouse platelets is
not known. Here, we use paired-end next-generation RNA sequencing
(RNA-seq) to characterize the polyadenylated transcriptomes of human
and mouse platelets. We report that RNA-seq provides unprecedented
resolution of mRNAs that are expressed across the entire human and
mouse genomes. Transcript expression and abundance are often conserved
between the 2 species. Several mRNAs, however, are differentially
expressed in human and mouse platelets. Moreover, previously described
functional disparities between mouse and human platelets are reflected
in differences at the transcript level, including protease activated
receptor-1, protease activated receptor-3, platelet activating factor
receptor, and factor V. This suggests that RNA-seq is a useful tool
for predicting differences in platelet function between mice and
humans. Our next-generation sequencing analysis provides new insights
into the human and murine platelet transcriptomes. The sequencing
dataset will be useful in the design of mouse models of hemostasis
and a catalyst for discovery of new functions of platelets. Access
to the dataset is found in the "Introduction."},
doi = {10.1182/blood-2011-03-339705},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/14/e101.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/14/e101}
}
@ARTICLE{Rowzee2009,
author = {Rowzee, Anne M. and Ludwig, Dale L. and Wood, Teresa L.},
title = {Insulin-Like Growth Factor Type 1 Receptor and Insulin Receptor Isoform
Expression and Signaling in Mammary Epithelial Cells},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {3611--3619},
number = {8},
month = aug,
abstract = {The insulin receptor (IR) isoforms and the IGF type 1 receptor (IGF-1R)
share a high degree of structural homology but differ in ligand binding
kinetics and functions. We developed a highly specific quantitative
PCR assay to quantify and compare IR-A, IR-B, and IGF-1R expression
within an RNA population. We determined receptor expression in primary
murine mammary epithelial cells (MECs) during postnatal development.
Both IR isoform mRNAs were 3- to 16-fold higher than IGF-1R expression
at all developmental times. IR protein was also 3- to 10-fold higher
than IGF-1R protein; however, significantly less IGF-1R was found
in hybrid receptors at early (49%) vs. late (79%) pregnancy, indicating
that the amount of hybrid receptor is developmentally regulated.
Despite high IR expression, IGF ligands were more effective than
insulin in stimulating the insulin receptor substrate-1/phosphatidylinositol
3-kinase/Akt pathway in acutely isolated MECs from virgin glands.
Although approximately 40% of IR transcripts were the IGF-II-sensitive
IR-A isoform, IGF-II failed to stimulate IR phosphorylation, and
an IGF-1R-specific blocking antibody completely abrogated IGF-II-mediated
Akt phosphorylation in the virgin MECs. Taken together, these data
suggest that the IGF-1R is more active in signaling than the IR and
is the predominant mediator of IGF actions in virgin MECs.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/8/3611}
}
@ARTICLE{Roxstrom-Lindquist2005,
author = {Roxstrom-Lindquist, Katarina and Ringqvist, Emma and Palm, Daniel
and Svard, Staffan},
title = {Giardia lamblia-Induced Changes in Gene Expression in Differentiated
Caco-2 Human Intestinal Epithelial Cells},
journal = {Infect. Immun.},
year = {2005},
volume = {73},
pages = {8204--8208},
number = {12},
month = dec,
abstract = {The parasitic protozoan Giardia lamblia is a worldwide cause of diarrhea,
but the mechanism of disease remains elusive. The parasite colonizes
the small intestinal epithelium, known to be a sensor for the presence
of enteric pathogens, without invading or causing severe inflammation.
In this study we investigated the epithelial cell response to G.
lamblia. Differentiated Caco-2 cells were infected with G. lamblia
isolate WB-A11, and the transcriptome of the intestinal cells was
analyzed after 1.5, 6, and 18 h of interaction, using oligonucleotide
microarrays. A large number of genes displayed changed expression
patterns, showing the complexity of the interaction between G. lamblia
and intestinal cells. A novel chemokine profile (CCL2, CCL20, CXCL1,
CXCL2, and CXCL3) was induced that was different from the response
induced by enteric pathogens causing intestinal inflammation. Several
genes involved in stress regulation changed their expression. These
findings indicate that the intestinal epithelium senses the G. lamblia
infection, and this is important for induction of innate and adaptive
immunity. The induced stress response can be important in the pathogenesis.},
url = {http://iai.asm.org/cgi/content/abstract/73/12/8204}
}
@ARTICLE{Roy2007,
author = {Roy, Nicole and Barnett, Matthew and Knoch, Bianca and Dommels, Yvonne
and McNabb, Warren},
title = {Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases:
Transcriptomic analysis of the effects of eicosapentaenoic acid-
and arachidonic acid-enriched diets},
journal = {Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis},
year = {2007},
volume = {622},
pages = {103--116},
number = {1-2},
month = sep,
abstract = {In vivo models of Inflammatory Bowel Diseases (IBD) elucidate important
mechanisms of chronic inflammation. Complex intestinal responses
to food components create a unique "fingerprint" discriminating health
from disease. Five-week-old IL10-/- and C57BL/6J (C57; control) mice
were inoculated orally with complex intestinal microflora (CIF) and/or
pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming
for more consistent inflammation of the intestinal mucosa. Inoculation
treatments were compared to non-inoculated IL10-/- and C57 mice,
either kept in specific pathogen free (SPF) or conventional conditions
(2 × 5 factorial design). At 12 weeks of age, mice were sacrificed
for intestinal histological (HIS) and transcriptomic analysis using
limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly
affected (P < 0.05) in inoculated IL10-/- mice and accounted for
approximately 60% of total intestinal HIS. Inoculation showed a strong
effect on colonic gene expression, with more than 2000 genes differentially
expressed in EF·CIF-inoculated IL10-/- mice. Immune response gene
expression was altered (P < 0.05) in these mice. The second study
investigated the effect of arachidonic (AA) and eicosapentaenoic
acid (EPA) on colonic HIS and gene expression to test whether EPA,
contrary to AA, diminished intestinal inflammation in EF·CIF IL10-/-
mice (2 × 4 factorial design). AIN-76A (5% corn oil) and AIN-76A
(fat-free) +1% corn oil supplemented with either 3.7% oleic acid
(OA), AA or EPA were used. IL10-/- mice fed EPA- and AA-enriched
diets had at least 40% lower colonic HIS (P < 0.05) than those fed
control diets (AIN-76A and OA diets). The expression of immune response
and [`]inflammatory disease' genes (down-regulated: TNF[alpha], IL6,
S100A8, FGF7, PTGS2; up-regulated: PPAR[alpha], MGLL, MYLK, PPSS23,
ABCB4 with EPA and/or AA) was affected in IL10-/- mice fed EPA- and
AA-enriched diets, compared to those fed AIN-76A diet.},
booktitle = {Nutrigenomics},
issn = {0027-5107},
keywords = {Inflammatory Bowel Diseases, IL10-/- mice, Colon, Gene expression,
Dietary polyunsaturated fatty acids},
url = {http://www.sciencedirect.com/science/article/B6T2C-4NJ0TTM-5/2/331def5ac12a57448d8403cb8ef48fac}
}
@BOOK{Roy2010,
title = {Genomics as a Tool to Characterize Anti-Inflammatory Nutraceuticals},
publisher = {Wiley-Blackwell},
year = {2010},
author = {Roy, Sashwati},
pages = {73--82},
abstract = {Summary 10.1002/9780813821474.ch7.abs This chapter contains sections
titled:},
booktitle = {Genomics, Proteomics, and Metabolomics in Nutraceuticals and Functional
Foods},
issn = {9780813821474},
keywords = {Genomics as a Tool to Characterize Anti-inflammatory Nutraceuticals,
chronic inflammation in disease, neurodegenerative diseases, nutraceuticals
in the management of chronic inflammation, human microvascular endothelial
cells (HMEC), Chronic stimulation of MMP activities, TNFα-inducible
expression of VCAM-1},
url = {http://dx.doi.org/10.1002/9780813821474.ch7}
}
@ARTICLE{Roy2009,
author = {Roy, Sashwati and Biswas, Sabyasachi and Khanna, Savita and Gordillo,
Gayle and Bergdall, Valerie and Green, Jeanne and Marsh, Clay B.
and Gould, Lisa J. and Sen, Chandan K.},
title = {Characterization of a preclinical model of chronic ischemic wound},
journal = {Physiol Genomics},
year = {2009},
volume = {37},
pages = {211--224},
number = {3},
month = may,
abstract = {Chronic ischemic wounds presenting at wound clinics are heterogeneous
with respect to etiology, age of the wound, and other factors complicating
wound healing. In addition, there are ethical challenges associated
with collecting repeated biopsies from a patient to develop an understanding
of the temporal dynamics of the mechanisms underlying chronic wounds.
The need for a preclinical model of ischemic wound is therefore compelling.
The porcine model is widely accepted as an excellent preclinical
model for human wounds. A full-thickness bipedicle flap approach
was adopted to cause skin ischemia. Closure of excisional wounds
placed on ischemic tissue was severely impaired resulting in chronic
wounds. Histologically, ischemic wounds suffered from impaired re-epithelialization,
delayed macrophage recruitment and poorer endothelial cell abundance
and organization. Compared with the pair-matched nonischemic wound,
unique aspects of the ischemic wound biology were examined on days
3, 7, 14, and 28 by systematic screening of the wound tissue transcriptome
using high-density porcine GeneChips. Ischemia markedly potentiated
the expression of arginase-1, a cytosolic enzyme that metabolizes
the precursor of nitric oxide L-arginine. Ischemia also induced the
SOD2 in the wound tissue perhaps as survival response of the challenged
tissue. Human chronic wounds also demonstrated elevated expression
of SOD2 and arginase-1. This study provides a thorough database that
may serve as a valuable reference tool to develop novel hypotheses
aiming to elucidate the biology of ischemic chronic wounds in a preclinical
setting.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/37/3/211}
}
@ARTICLE{Roy2006,
author = {Roy, Sashwati and Khanna, Savita and Kuhn, Donald E. and Rink, Cameron
and Williams, Willis T. and Zweier, Jay L. and Sen, Chandan K.},
title = {Transcriptome analysis of the ischemia-reperfused remodeling myocardium:
temporal changes in inflammation and extracellular matrix},
journal = {Physiol Genomics},
year = {2006},
volume = {25},
pages = {364--374},
number = {3},
month = may,
abstract = {cDNA microarray analysis was performed to screen 15,000 genes and
expressed sequence tags (ESTs) to identify changes in the ischemia-reperfused
(I-R) rat myocardial transcriptome in the early (day 2) and late
(day 7) inflammatory phases of acute myocardial infarction. Lists
of candidate genes that were affected by I-R transiently (2 or 7
days only) or on a more sustained basis (2 and 7 days) were derived.
The candidate genes represented three major functional categories:
extracellular matrix, apoptosis, and inflammation. To expand on the
findings from microarray studies that dealt with the two above-mentioned
time points, tissues collected from days 0, 0.25, 2, 3, 5, and 7
after reperfusion were examined. Acute myocardial infarction resulted
in upregulation of IL-6 and IL-18. Genes encoding extracellular matrix
proteins such as types I and III collagen were upregulated in day
2, and that response progressively grew stronger until day 7 after
I-R. Comparable response kinetics was exhibited by the candidate
genes of the apoptosis category. Caspases-2, -3, and -8 were induced
in response to acute infarction. Compared with the myocardial tissue
from the sham-operated rats, tissue collected from the infarct region
stained heavily positive for the presence of active caspase-3. Laser
microdissection and pressure catapulting technology was applied to
harvest infarct and adjacent noninfarct control tissue from a microscopically
defined region in the rat myocardium. Taken together, this work presents
the first evidence gained from the use of DNA microarrays to understand
the molecular mechanisms implicated in the early and late inflammatory
phases of the I-R heart.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/25/3/364}
}
@ARTICLE{Roy2008,
author = {Roy, Sashwati and Khanna, Savita and Rink, Cameron and Biswas, Sabyasachi
and Sen, Chandan K.},
title = {Characterization of the acute temporal changes in excisional murine
cutaneous wound inflammation by screening of the wound-edge transcriptome},
journal = {Physiol Genomics},
year = {2008},
volume = {34},
pages = {162--184},
number = {2},
month = jul,
abstract = {This work represents a maiden effort to systematically screen the
transcriptome of the healing wound-edge tissue temporally using high-density
GeneChips. Changes during the acute inflammatory phase of murine
excisional wounds were characterized histologically. Sets of genes
that significantly changed in expression during healing could be
segregated into the following five sets: up-early (6-24 h; cytokine-cytokine
receptor interaction pathway), up-intermediary (12-96 h; leukocyte-endothelial
interaction pathway), up-late (48-96 h; cell-cycle pathway), down-early
(6-12 h; purine metabolism) and down-intermediary (12-96 h; oxidative
phosphorylation pathway). Results from microarray and real-time PCR
analyses were consistent. Results listing all genes that were significantly
changed at any specific time point were further mined for cell-type
(neutrophils, macrophages, endothelial, fibroblasts, and pluripotent
stem cells) specificity. Candidate genes were also clustered on the
basis of their functional annotation, linking them to inflammation,
angiogenesis, reactive oxygen species (ROS), or extracellular matrix
(ECM) categories. Rapid induction of genes encoding NADPH oxidase
subunits and downregulation of catalase in response to wounding is
consistent with the fact that low levels of endogenous H2O2 is required
for wound healing. Angiogenic genes, previously not connected to
cutaneous wound healing, that were induced in the healing wound-edge
included adiponectin, epiregulin, angiomotin, Nogo, and VEGF-B. This
study provides a digested database that may serve as a valuable reference
tool to develop novel hypotheses aiming to elucidate the biology
of cutaneous wound healing comprehensively.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/34/2/162}
}
@ARTICLE{Royaee2004,
author = {Royaee, Atabak R. and Husmann, Robert J. and Dawson, Harry D. and
Calzada-Nova, Gabriela and Schnitzlein, William M. and Zuckermann,
Federico A. and Lunney, Joan K.},
title = {Deciphering the involvement of innate immune factors in the development
of the host response to PRRSV vaccination},
journal = {Veterinary Immunology and Immunopathology},
year = {2004},
volume = {102},
pages = {199--216},
number = {3},
month = dec,
abstract = {The natural response of pigs to porcine reproductive and respiratory
syndrome virus (PRRSV) infections and vaccinations needs to be altered
so that better protection is afforded against both homologous and
heterologous challenges by this pathogen. To address this problem,
real-time gene expression assays were coupled with cytokine Elispot
and protein analyses to assess the nature of the anti-PRRSV response
of pigs immunized with modified live virus (MLV) vaccine. Although
T helper 1 (Th1) immunity was elicited in all vaccinated animals,
as evidenced by the genesis of PRRSV-specific interferon-gamma secreting
cells (IFNG SC), the overall extent of the memory response was variable
and generally weak. Peripheral blood mononuclear cells (PBMC) isolated
from these pigs responded to PRRSV exposure with a limited increase
in their expression of the Th1 immune markers, IFNG, tumor necrosis
factor-alpha and interleukin-15 (IL15), and a reduction in the quantity
of mRNAs encoding the innate and inflammatory proteins, IL1B, IL8
and IFNA. Efforts to enhance Th1 immunity, by utilizing an expression
plasmid encoding porcine IFNA (pINA) as an adjuvant, resulted in
a temporary increase in the frequency of PRRSV-specific IFNG SC but
only minor changes overall in the expression of Th1 associated cytokine
or innate immune marker mRNA by virus-stimulated PBMC. Administration
of pINA, however, did correlate with decreased IL1B secretion by
cultured, unstimulated PBMC but had no effect on their ability to
release IFNG. Thus, while exogenous addition of IFNA during PRRSV
vaccination has an impact on the development of a Th1 immune response,
other alterations will be required for substantial boosting of virus-specific
protection.},
booktitle = {PRRS Immunology and Immunopathology Special Issue},
issn = {0165-2427},
keywords = {Swine, Cytokine gene regulation, T helper 1 immunity, anti-PRRSV immunity,
IFNA adjuvant, Inflammatory cytokines},
url = {http://www.sciencedirect.com/science/article/B6TD5-4DMWDTM-3/2/4eb70f9e88fa6fb8940914cd1470d51c}
}
@ARTICLE{Roychowdhury2011,
author = {Roychowdhury, Sameek and Iyer, Matthew K. and Robinson, Dan R. and
Lonigro, Robert J. and Wu, Yi-Mi and Cao, Xuhong and Kalyana-Sundaram,
Shanker and Sam, Lee and Balbin, O. Alejandro and Quist, Michael
J. and Barrette, Terrence and Everett, Jessica and Siddiqui, Javed
and Kunju, Lakshmi P. and Navone, Nora and Araujo, John C. and Troncoso,
Patricia and Logothetis, Christopher J. and Innis, Jeffrey W. and
Smith, David C. and Lao, Christopher D. and Kim, Scott Y. and Roberts,
J. Scott and Gruber, Stephen B. and Pienta, Kenneth J. and Talpaz,
Moshe and Chinnaiyan, Arul M.},
title = {Personalized Oncology Through Integrative High-Throughput Sequencing:
A Pilot Study},
journal = {Science Translational Medicine},
year = {2011},
volume = {3},
pages = {111ra121},
number = {111},
abstract = {Individual cancers harbor a set of genetic aberrations that can be
informative for identifying rational therapies currently available
or in clinical trials. We implemented a pilot study to explore the
practical challenges of applying high-throughput sequencing in clinical
oncology. We enrolled patients with advanced or refractory cancer
who were eligible for clinical trials. For each patient, we performed
whole-genome sequencing of the tumor, targeted whole-exome sequencing
of tumor and normal DNA, and transcriptome sequencing (RNA-Seq) of
the tumor to identify potentially informative mutations in a clinically
relevant time frame of 3 to 4 weeks. With this approach, we detected
several classes of cancer mutations including structural rearrangements,
copy number alterations, point mutations, and gene expression alterations.
A multidisciplinary Sequencing Tumor Board (STB) deliberated on the
clinical interpretation of the sequencing results obtained. We tested
our sequencing strategy on human prostate cancer xenografts. Next,
we enrolled two patients into the clinical protocol and were able
to review the results at our STB within 24 days of biopsy. The first
patient had metastatic colorectal cancer in which we identified somatic
point mutations in NRAS, TP53, AURKA, FAS, and MYH11, plus amplification
and overexpression of cyclin-dependent kinase 8 (CDK8). The second
patient had malignant melanoma, in which we identified a somatic
point mutation in HRAS and a structural rearrangement affecting CDKN2C.
The STB identified the CDK8 amplification and Ras mutation as providing
a rationale for clinical trials with CDK inhibitors or MEK (mitogen-activated
or extracellular signal-regulated protein kinase kinase) and PI3K
(phosphatidylinositol 3-kinase) inhibitors, respectively. Integrative
high-throughput sequencing of patients with advanced cancer generates
a comprehensive, individual mutational landscape to facilitate biomarker-driven
clinical trials in oncology.},
doi = {10.1126/scitranslmed.3003161},
eprint = {http://stm.sciencemag.org/cgi/reprint/3/111/111ra121.pdf},
url = {http://stm.sciencemag.org/cgi/content/abstract/3/111/111ra121}
}
@ARTICLE{Royer2011,
author = {Royer, Corinne and Briolay, Jérôme and Garel, Annie and Brouilly,
Patrick and Sasanuma, Shun-ichi and Sasanuma, Motoe and Shimomura,
Michihiko and Keime, Céline and Gandrillon, Olivier and Huang, Yongping
and Chavancy, Gérard and Mita, Kazuei and Couble, Pierre},
title = {Novel genes differentially expressed between posterior and median
silk gland identified by SAGE-aided transcriptome analysis},
journal = {Insect Biochemistry and Molecular Biology},
year = {2011},
volume = {41},
pages = {118--124},
number = {2},
month = feb,
abstract = {Serial analysis of gene expression (SAGE) profiles, from posterior
and median cells of the silk gland of Bombyx mori, were analyzed
and compared, so as to identify their respective distinguishing functions.
The annotation of the SAGE libraries was performed with a B. mori
reference tag collection, which was extracted from a novel set of
Bombyx ESTs, sequenced from the 3' side. Most of the tags appeared
at similar relative concentration within the two libraries, and corresponded
with region-specific and highly abundant silk proteins. Strikingly,
in addition to tags from silk protein mRNAs, 19 abundant tags were
found (>=0.1%), in the median cell library, which were absent in
the posterior cell tag collection. With the exception of tags from
SP1 mRNA, no PSG specific tags were found in this subset class. The
analysis of some of the MSG-specific transcripts, suggested that
middle silk gland cells have diversified functions, in addition to
their well characterized role in silk sericins synthesis and secretion.},
issn = {0965-1748},
keywords = {Bombyx, Silk gland, Transcriptome, SAGE},
url = {http://www.sciencedirect.com/science/article/pii/S0965174810002390}
}
@ARTICLE{Royland2008,
author = {Royland, Joyce E. and Kodavanti, Prasada Rao S.},
title = {Gene expression profiles following exposure to a developmental neurotoxicant,
Aroclor 1254: Pathway analysis for possible mode(s) of action},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {231},
pages = {179--196},
number = {2},
month = sep,
abstract = {Epidemiological studies indicate that low levels of polychlorinated
biphenyl (PCB) exposure can adversely affect neurocognitive development.
In animal models, perturbations in calcium signaling, neurotransmitters,
and thyroid hormones have been postulated as potential mechanisms
for PCB-induced developmental neurotoxicity. In order to understand
the role of these proposed mechanisms and to identify other mechanisms
in PCB-induced neurotoxicity, we have chosen a global approach utilizing
oligonucleotide microarrays to examine gene expression profiles in
the brain following developmental exposure to Aroclor 1254 (0 or
6 mg/kg/day from gestation day 6 through postnatal day (PND) 21)
in Long-Evans rats. Gene expression levels in the cerebellum and
hippocampus from PNDs 7 and 14 animals were determined on Affymetrix
rat 230A_2.0 chips. In the cerebellum, 87 transcripts were altered
at PND7 compared to 27 transcripts at PND14 by Aroclor 1254 exposure,
with only one transcript affected at both ages. In hippocampus, 175
transcripts and 50 transcripts were altered at PND7 and PND14, respectively,
by Aroclor 1254 exposure with five genes commonly affected. Functional
analysis suggests that pathways related to calcium homeostasis (Gng3,
Ryr2, Trdn, Cacna1a), intracellular signaling (Camk2d, Stk17b, Pacsin2,
Ryr2, Trio, Fert2, Ptk2b), axonal guidance (Lum, Mxd3, Akap11, Gucy1b3),
aryl hydrocarbon receptor signaling (Nfia, Col1a2), and transcripts
involved in cell proliferation (Gspt2, Cdkn1c, Ptk2b) and differentiation
(Ifitm31, Hpca, Zfp260, Igsf4a, Hes5) leading to the development
of nervous system were significantly altered by Aroclor 1254 exposure.
Of the two brain regions examined, Aroclor 1254-induced genomic changes
were greater in the hippocampus than the cerebellum. The genomic
data suggests that PCB-induced neurotoxic effects were due to disruption
of normal ontogenetic pattern of nervous system growth and development
by altering intracellular signaling pathways but not by endocrine
disruption.},
issn = {0041-008X},
keywords = {Polychlorinated biphenyls, Genomics, Nervous system development, Aroclor
1254, Learning and memory, Mode of action, Calcium signaling},
url = {http://www.sciencedirect.com/science/article/B6WXH-4SFG4JT-2/2/26927ecab526ede0c44b14572e6a5f09}
}
@ARTICLE{Royland2008a,
author = {Royland, J. E. and Parker, J. S. and Gilbert, M. E.},
title = {A Genomic Analysis of Subclinical Hypothyroidism in Hippocampus and
Neocortex of the Developing Rat Brain},
journal = {Journal of Neuroendocrinology},
year = {2008},
volume = {20},
pages = {1319--1338},
number = {12},
abstract = {Hypothyroidism during pregnancy and the early postnatal period has
severe neurological consequences for the developing offspring. The
impact of milder degrees of perturbation of the thyroid axis as encompassed
in conditions of subclinical hypothyroidism and hypothyroxinemia,
however, has not been established. The present investigation examined
the effects of graded levels of hypothyroidism, from subclinical
to severe, on global gene expression in the developing rodent brain.
Thyroid hormone insufficiency was induced by administration of propylthiouracil
(PTU) to pregnant rats via drinking water from gestational day 6
until sacrifice of pups prior to weaning. In the first study a specialised
microarray, the Affymetrix Rat Neurobiology array RN_U34, was used
to contrast gene expression in the hippocampus of animals exposed
to 0 or 10Â ppm (10Â mg/l) PTU, a treatment producing severe hypothyroidism.
In the second study, a more complete genome array (Affymetrix Rat
230A) was used to compare gene expression in the neocortex and hippocampus
of postnatal day (PN) 14 animals experiencing graded degrees of thyroid
hormone insufficiency induced by delivery of 0, 1, 2 or 3Â ppm PTU
to the dam. Dose-dependent up- and down-regulation were observed
for gene transcripts known to play critical roles in brain development
and brain function. Expression levels of a subset of approximately
25 genes in each brain region were altered at a dose of PTU (1Â ppm)
that induced mild hypothyroxinemia in dams and pups. These data indicate
that genes driving important developmental processes are sensitive
to relatively modest perturbations of the thyroid axis, and that
the level of gene expression is related to the degree of hormone
reduction. Altered patterns of gene expression during critical windows
of brain development indicate that thyroid disease must be viewed
as a continuum and that conditions typically considered ‘subclinical’
may induce structural and functional abnormalities in the developing
central nervous system.},
issn = {1365-2826},
keywords = {propylthiouracil, genomics, cortex, hippocampus, subclinical hypothyroidism},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2826.2008.01793.x}
}
@ARTICLE{Royland2008b,
author = {Royland, Joyce E. and Wu, Jinfang and Zawia, Nasser H. and Kodavanti,
Prasada Rao S.},
title = {Gene expression profiles in the cerebellum and hippocampus following
exposure to a neurotoxicant, Aroclor 1254: Developmental effects},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {231},
pages = {165--178},
number = {2},
month = sep,
abstract = {The developmental consequences of exposure to the polychlorinated
biphenyls (PCBs) have been widely studied, making PCBs a unique model
to understand issues related to environmental mixture of persistent
chemicals. PCB exposure in humans adversely affects neurocognitive
development, causes psychomotor difficulties, and contributes to
attention deficits in children, all of which seem to be associated
with altered patterns of neuronal connectivity. In the present study,
we examined gene expression profiles in the rat nervous system following
PCB developmental exposure. Pregnant rats (Long-Evans) were dosed
perinatally with 0 or 6 mg/kg/day of Aroclor 1254 from gestation
day 6 through postnatal day (PND) 21. Gene expression in cerebellum
and hippocampus from PND7 and PND14 animals was analyzed with an
emphasis on developmental aspects. Changes in gene expression (>= 1.5
fold) in control animals identified normal developmental changes.
These basal levels of expression were compared to data from Aroclor
1254-treated animals to determine the impact of gestational PCB exposure
on developmental parameters. The results indicate that the expression
of a number of developmental genes related to cell cycle, synaptic
function, cell maintenance, and neurogenesis is significantly altered
from PND7 to PND14. Aroclor 1254 treatment appears to dampen the
overall growth-related gene expression levels in both regions with
the effect being more pronounced in the cerebellum. Functional analysis
suggests that Aroclor 1254 delays maturation of the developing nervous
system, with the consequences dependent on the ontological state
of the brain area and the functional role of the individual gene.
Such changes may underlie learning and memory deficits observed in
PCB exposed animals and humans.},
issn = {0041-008X},
keywords = {Polychlorinated biphenyls, Genomics, Nervous system, Development,
Aroclor 1254, Learning and memory},
url = {http://www.sciencedirect.com/science/article/B6WXH-4SFG4JT-1/2/eb99a6f0e23e9055be5ed222a5dc236b}
}
@ARTICLE{Roymans2004,
author = {Roymans, Dirk and Van Looveren, Cis and Leone, Angelique and Parker,
J. Brandon and McMillian, Michael and Johnson, Mark D. and Koganti,
Aruna and Gilissen, Ron and Silber, Paul and Mannens, Geert and Meuldermans,
Willem},
title = {Determination of cytochrome P450 1A2 and cytochrome P450 3A4 induction
in cryopreserved human hepatocytes},
journal = {Biochemical Pharmacology},
year = {2004},
volume = {67},
pages = {427--437},
number = {3},
month = feb,
abstract = {Freshly prepared human hepatocytes are considered as the [`]gold standard'
for in vitro testing of drug candidates. However, several disadvantages
are associated with the use of this model system. The availability
of hepatocytes is often low and consequently the planning of the
experiments rendered difficult. In addition, the quality of the available
cells is in some cases poor. As an alternative, cryopreserved human
hepatocytes were validated as a model to study cytochrome P450 1A2
(CYP1A2) and cytochrome P450 3A4 (CYP3A4) induction. In a single
blinded experiment, hepatocytes from three separate lots were incubated
with three concentrations of different compounds, and compared to
non-treated cells and cells incubated with omeprazole or rifampicin.
CYP1A2 and CYP3A4 induction was determined by measuring 7-ethoxyresorufin-O-deethylation
activity and 6[beta]-hydroxytestosterone formation, respectively.
CYP1A2 and CYP3A4 mRNA and protein expression were analyzed by TaqMan
QRT-PCR and immunodetection. Cells responded well to the prototypical
inducers with a mean 38.8- and 6.2-fold induction of CYP1A2 and CYP3A4
activity, respectively. Similar as with fresh human hepatocytes,
high batch-to-batch variation of CYP1A2 and CYP3A4 induction was
observed. Except for 1 and 10 [mu]M rosiglitazone, the glitazones
did not significantly affect CYP1A2. A similar result was observed
for CYP3A4 activity although CYP3A4 mRNA and protein expression were
dose-dependently upregulated. In conclusion, cryopreserved human
hepatocytes may be a good alternative to fresh hepatocytes to study
CYP1A and 3A induction.},
issn = {0006-2952},
keywords = {Cytochrome P450, CYP1A2, CYP3A4, Induction, Human hepatocytes, Gene
and protein expression},
url = {http://www.sciencedirect.com/science/article/B6T4P-4BRCNCP-6/2/4b8efa1831087b2c3f3c9403a6f9805d}
}
@ARTICLE{Roze2007,
author = {Roze, Ludmila V. and Arthur, Anna E. and Hong, Sung-Yong and Chanda,
Anindya and Linz, John E.},
title = {The initiation and pattern of spread of histone H4 acetylation parallel
the order of transcriptional activation of genes in the aflatoxin
cluster},
journal = {Molecular Microbiology},
year = {2007},
volume = {66},
pages = {713--726},
number = {3},
abstract = {Summary The 27 genes involved in aflatoxin biosynthesis are clustered
within a 70Â kb region in the Aspergillus parasiticus genome. Using
chromatin immunoprecipitation, we demonstrated a positive correlation
between the initiation and spread of histone H4 acetylation in aflatoxin
promoters and the onset of accumulation of aflatoxin proteins and
aflatoxin. Histone H4 acetylation in the pksA (encodes an ‘early’
biosynthetic pathway enzyme) promoter peaked at 30Â h, prior to the
increased acetylation in the omtA and ordA (encode ‘late’ enzymes)
promoters detected at 40Â h. The specific order in which pksA, ver-1
(encodes a ‘middle’ enzyme) and omtA transcripts accumulated
in cells paralleled the pattern of spread of histone H4 acetylation.
Binding of AflR, a positive regulator of aflatoxin biosynthesis,
to the ordA promoter showed a positive correlation with the spread
of histone H4 acetylation. The data suggest that the order of genes
within the aflatoxin cluster determines the timing and order of transcriptional
activation, and that the site of initiation and spread of histone
H4 acetylation mediate this process. Our data indicate that the aflatoxin
and adjacent sugar utilization clusters are part of a larger ‘regulatory
unit’.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2007.05952.x}
}
@ARTICLE{Roze2007a,
author = {Roze, Ludmila V. and Beaudry, Randolph M. and Arthur, Anna E. and
Calvo, Ana M. and Linz, John E.},
title = {Aspergillus Volatiles Regulate Aflatoxin Synthesis and Asexual Sporulation
in Aspergillus parasiticus},
journal = {Appl. Envir. Microbiol.},
year = {2007},
volume = {73},
pages = {7268--7276},
number = {22},
month = nov,
abstract = {Aspergillus parasiticus is one primary source of aflatoxin contamination
in economically important crops. To prevent the potential health
and economic impacts of aflatoxin contamination, our goal is to develop
practical strategies to reduce aflatoxin synthesis on susceptible
crops. One focus is to identify biological and environmental factors
that regulate aflatoxin synthesis and to manipulate these factors
to control aflatoxin biosynthesis in the field or during crop storage.
In the current study, we analyzed the effects of aspergillus volatiles
on growth, development, aflatoxin biosynthesis, and promoter activity
in the filamentous fungus A. parasiticus. When colonies of Aspergillus
nidulans and A. parasiticus were incubated in the same growth chamber,
we observed a significant reduction in aflatoxin synthesis and asexual
sporulation by A. parasiticus. Analysis of the headspace gases demonstrated
that A. nidulans produced much larger quantities of 2-buten-1-ol
(CA) and 2-ethyl-1-hexanol (EH) than A. parasiticus. In its pure
form, EH inhibited growth and increased aflatoxin accumulation in
A. parasiticus at all doses tested; EH also stimulated aflatoxin
transcript accumulation. In contrast, CA exerted dose-dependent up-regulatory
or down-regulatory effects on aflatoxin accumulation, conidiation,
and aflatoxin transcript accumulation. Experiments with reporter
strains carrying nor-1 promoter deletions and mutations suggested
that the differential effects of CA were mediated through separate
regulatory regions in the nor-1 promoter. The potential efficacy
of CA as a tool for analysis of transcriptional regulation of aflatoxin
biosynthesis is discussed. We also identify a novel, rapid, and reliable
method to assess norsolorinic acid accumulation in solid culture
using a Chroma Meter CR-300 apparatus.},
url = {http://aem.asm.org/cgi/content/abstract/73/22/7268}
}
@ARTICLE{RozpAe™dowska2011,
author = {Rozpędowska, Elżbieta and Hellborg, Linda and Ishchuk, Olena P.
and Orhan, Furkan and Galafassi, Silvia and Merico, Annamaria and
Woolfit, Megan and Compagno, Concetta and Piškur, Jure},
title = {Parallel evolution of the make–accumulate–consume strategy in
Saccharomyces and Dekkera yeasts},
journal = {Nat Commun},
year = {2011},
volume = {2},
pages = {302--},
month = may,
comment = {10.1038/ncomms1305},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/ncomms1305}
}
@ARTICLE{Ruan2008,
author = {Ruan, Daniel T. and Warren, Robert S. and Moalem, Jacob and Chung,
Ki-Wook and Griffin, Ann C. and Shen, Wen and Duh, Quan-Yang and
Nakakura, Eric and Donner, David B. and Khanafshar, Elham and Weng,
Julie and Clark, Orlo H. and Kebebew, Electron},
title = {Mitogen-inducible gene-6 expression correlates with survival and
is an independent predictor of recurrence in BRAFV600E positive papillary
thyroid cancers},
journal = {Surgery},
year = {2008},
volume = {144},
pages = {908--914},
number = {6},
month = dec,
abstract = {Background Mitogen-inducible gene-6 (Mig-6) is an immediate early
response gene that negatively regulates signaling. EGFR overexpression
and activating mutations in MAPK signaling effectors are common events
in papillary thyroid cancer (PTC). The purpose of this study was
to determine if Mig-6 expression is associated with EGFR expression
or surgical outcomes in PTC.Methods We determined Mig-6 transcript
levels from a microarray in 19 patients with PTC who underwent thyroidectomy.
We established a maximally selected cutoff to discriminate Kaplan-Meier
survival estimates. For cross-validation, we performed quantitative
RT-PCR on resected well-differentiated PTC from an additional 106
patients.Results Mig-6 and EGFR mRNA levels correlated directly (P
< .0001). Mig-6 expression above the cutoff of 1.10 (2^-dCt[Mig6-GUS])
was associated with greater survival (P = .008). When this cutoff
was applied in the cross-validation, high Mig-6 expression was associated
with longer survival (P = .03) and disease-free survival (P = .07).
Furthermore, high Mig-6 expression was independently predictive of
greater disease-free survival in BRAFV600E-positive PTC.Conclusion
High Mig-6 expression in PTC is associated with favorable outcomes.
Mig-6 is a novel tumor suppressor that may be a candidate for targeted
cancer therapeutics in patients with PTC refractory to conventional
therapy.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4V15XKP-F/2/2ff554b43a25cffdb33fa34e814fa576}
}
@ARTICLE{Ruan2011,
author = {Ruan, Lifang and Pleitner, Aaron and Ganzle, Michael G. and McMullen,
Lynn M.},
title = {Solute Transport Proteins and the Outer Membrane Protein NmpC Contribute
to Heat Resistance of Escherichia coli AW1.7},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {2961--2967},
number = {9},
month = may,
abstract = {This study aimed to elucidate determinants of heat resistance in Escherichia
coli by comparing the composition of membrane lipids, as well as
gene expression, in heat-resistant E. coli AW1.7 and heat-sensitive
E. coli GGG10 with or without heat shock. The survival of E. coli
AW1.7 at late exponential phase was 100-fold higher than that of
E. coli GGG10 after incubation at 60{degrees}C for 15 min. The cytoplasmic
membrane of E. coli AW1.7 contained a higher proportion of saturated
and cyclopropane fatty acids than that of E. coli GGG10. Microarray
hybridization of cDNA libraries obtained from exponentially growing
or heat-shocked cultures was performed to compare gene expression
in these two strains. Expression of selected genes from different
functional groups was quantified by quantitative PCR. DnaK and 30S
and 50S ribosomal subunits were overexpressed in E. coli GGG10 relative
to E. coli AW1.7 upon heat shock at 50{degrees}C, indicating improved
ribosome stability. The outer membrane porin NmpC and several transport
proteins were overexpressed in exponentially growing E. coli AW1.7.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
of membrane properties confirmed that NmpC is present in the outer
membrane of E. coli AW1.7 but not in that of E. coli GGG10. Expression
of NmpC in E. coli GGG10 increased survival at 60{degrees}C 50- to
1,000-fold. In conclusion, the outer membrane porin NmpC contributes
to heat resistance in E. coli AW1.7, but the heat resistance of this
strain is dependent on additional factors, which likely include the
composition of membrane lipids, as well as solute transport proteins.},
comment = {10.1128/AEM.01930-10},
url = {http://aem.asm.org/cgi/content/abstract/77/9/2961}
}
@ARTICLE{Rubbia-Brandt2011,
author = {Rubbia-Brandt, Laura and Tauzin, Sebastien and Brezault, Catherine
and Delucinge-Vivier, Celine and Descombes, Patrick and Dousset,
Bertand and Majno, Pietro E. and Mentha, Gilles and Terris, Benoit},
title = {Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related
Sinusoidal Obstruction Syndrome in Humans},
journal = {Mol. Cancer Ther.},
year = {2011},
volume = {10},
pages = {687--696},
number = {4},
month = apr,
abstract = {Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease)
is a well-established complication of hematopoietic stem cell transplantation,
pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic
agents such as oxaliplatin. It is associated with substantial morbidity
and mortality. Pathogenesis of SOS in humans is poorly understood.
To explore its molecular mechanisms, we used Affymetrix U133 Plus
2.0 microarrays to investigate the gene expression profile of 11
human livers with oxaliplatin-related SOS and compared it to 12 matched
controls. Hierarchical clustering analysis showed that profiles from
SOS and controls formed distinct clusters. To identify functional
networks and gene ontologies, data were analyzed by the Ingenuity
Pathway Analysis Tool. A total of 913 genes were differentially expressed
in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR
results showed excellent concordance with microarray data. Pathway
analysis showed major gene upregulation in six pathways in SOS compared
with controls: acute phase response (notably interleukin 6), coagulation
system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate
cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative
stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were
upregulated. The most significant increase was seen in CCL20 mRNA.
In conclusion, oxaliplatin-related SOS can be readily distinguished
according to morphologic characteristics but also by a molecular
signature. Global gene analysis provides new insights into mechanisms
underlying chemotherapy-related hepatotoxicity in humans and potential
targets relating to its diagnosis, prevention, and treatment. Activation
of VEGF and coagulation (vWF) pathways could partially explain at
a molecular level the clinical observations that bevacizumab and
aspirin have a preventive effect in SOS. Mol Cancer Ther; 10(4);
687-96. (C)2011 AACR.},
comment = {10.1158/1535-7163.MCT-10-1072},
url = {http://mct.aacrjournals.org/cgi/content/abstract/10/4/687}
}
@ARTICLE{Rubins2005,
author = {Rubins, Nir E. and Friedman, Joshua R. and Le, Phillip P. and Zhang,
Liping and Brestelli, John and Kaestner, Klaus H.},
title = {Transcriptional Networks in the Liver: Hepatocyte Nuclear Factor
6 Function Is Largely Independent of Foxa2},
journal = {Mol. Cell. Biol.},
year = {2005},
volume = {25},
pages = {7069--7077},
number = {16},
month = aug,
abstract = {A complex network of hepatocyte nuclear transcription factors, including
HNF6 and Foxa2, regulates the expression of liver-specific genes.
The current model, based on in vitro studies, suggests that HNF6
and Foxa2 interact physically. This interaction is thought to synergistically
stimulate Foxa2-dependent transcription through the recruitment of
p300/CBP by HNF6 and to inhibit HNF6-mediated transcription due to
the interference of Foxa2 with DNA binding by HNF6. To test this
model in vivo, we utilized hepatocyte-specific gene ablation to study
the binding of HNF6 to its targets in the absence of Foxa2. Chromatin
immunoprecipitation using anti-HNF6 antibodies was performed on chromatin
isolated from Foxa2loxP/loxP Alfp.Cre and control mouse livers, and
HNF6 binding to its target, Glut2, was determined by quantitative
PCR. In contrast to the current model, we found no significant difference
in HNF6 occupancy at the Glut2 promoter between Foxa2-deficient and
control livers. In order to evaluate the Foxa2/HNF6 interaction model
on a global scale, we performed a location analysis using a microarray
with 7,000 mouse promoter fragments. Again, we found no evidence
that HNF6 binding to its targets in chromatin is reduced in the presence
of Foxa2. We also examined the mRNA levels of HNF6 targets in the
liver using a cDNA array and found that their expression was similar
in Foxa2-deficient and control mice. Overall, our studies demonstrate
that HNF6 binds to and regulates its target promoters in vivo in
the presence and absence of Foxa2.},
url = {http://mcb.asm.org/cgi/content/abstract/25/16/7069}
}
@ARTICLE{Rubio2008,
author = {Rubio, Daniel and Garcia, Silvia and De la Cueva, Teresa and Paz,
M F. and Lloyd, Alison C. and Bernad, Antonio and Garcia-Castro,
Javier},
title = {Human mesenchymal stem cell transformation is associated with a mesenchymal-epithelial
transition},
journal = {Experimental Cell Research},
year = {2008},
volume = {314},
pages = {691--698},
number = {4},
month = feb,
abstract = {Carcinomas are widely thought to derive from epithelial cells with
malignant progression often associated with an epithelial-mesenchymal
transition (EMT). We have characterized tumors generated by spontaneously
transformed human mesenchymal cells (TMC) previously obtained in
our laboratory. Immunohistopathological analyses identified these
tumors as poorly differentiated carcinomas, suggesting that a mesenchymal-epithelial
transition (MET) was involved in the generation of TMC. This was
corroborated by microarray and protein expression analysis that showed
that almost all mesenchymal-related genes were severely repressed
in these TMC. Interestingly, TMC also expressed embryonic antigens
and were able to integrate into developing blastocysts with no signs
of tumor formation, suggesting a dedifferentiation process was associated
with the mesenchymal stem cell (MSC) transformation. These findings
support the hypothesis that some carcinomas are derived from mesenchymal
rather than from epithelial precursors.},
issn = {0014-4827},
keywords = {Transformation, Tumor, Mesenchymal stem cell},
url = {http://www.sciencedirect.com/science/article/B6WFC-4R7NR86-1/2/033c95389257f137a6b641bb0e536327}
}
@ARTICLE{Rubio-Aliaga2011,
author = {Rubio-Aliaga, Isabel and Roos, Baukje de and Sailer, Manuela and
McLoughlin, Gerard A. and Boekschoten, Mark V. and van Erk, Marjan
and Bachmair, Eva-Maria and van Schothorst, Evert M. and Keijer,
Jaap and Coort, Susan L. and Evelo, Chris and Gibney, Michael J.
and Daniel, Hannelore and Muller, Michael and Kleemann, Robert and
Brennan, Lorraine},
title = {Alterations in hepatic one-carbon metabolism and related pathways
following a high-fat dietary intervention},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {408--416},
number = {8},
month = apr,
abstract = {Obesity frequently leads to insulin resistance and the development
of hepatic steatosis. To characterize the molecular changes that
promote hepatic steatosis, transcriptomics, proteomics, and metabolomics
technologies were applied to liver samples from C57BL/6J mice obtained
from two independent intervention trials. After 12 wk of high-fat
feeding the animals became obese, hyperglycemic, and insulin resistant,
had elevated levels of blood cholesterol and VLDL, and developed
hepatic steatosis. Nutrigenomic analysis revealed alterations of
key metabolites and enzyme transcript levels of hepatic one-carbon
metabolism and related pathways. The hepatic oxidative capacity and
the lipid milieu were significantly altered, which may play a key
role in the development of insulin resistance. Additionally, high
choline levels were observed after the high-fat diet. Previous studies
have linked choline levels with insulin resistance and hepatic steatosis
in conjunction with changes of certain metabolites and enzyme levels
of one-carbon metabolism. The present results suggest that the coupling
of high levels of choline and low levels of methionine plays an important
role in the development of insulin resistance and liver steatosis.
In conclusion, the complexities of the alterations induced by high-fat
feeding are multifactorial, indicating that the interplay between
several metabolic pathways is responsible for the pathological consequences.},
comment = {10.1152/physiolgenomics.00179.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/8/408}
}
@ARTICLE{Rubiolo2009,
author = {Rubiolo, Patrizia and Matteodo, Maura and Bicchi, Carlo and Appendino,
Giovanni and Gnavi, Giorgio and Bertea, Cinzia and Maffei, Massimo},
title = {Chemical and Biomolecular Characterization of Artemisia umbelliformis
Lam., an Important Ingredient of the Alpine Liqueur “Genepì�},
journal = {Journal of Agricultural and Food Chemistry},
year = {2009},
volume = {57},
pages = {3436-3443},
number = {9},
note = {PMID: 19326948},
doi = {10.1021/jf803915v},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf803915v},
url = {http://pubs.acs.org/doi/abs/10.1021/jf803915v}
}
@ARTICLE{Rubtsov2011,
author = {Rubtsov, Anatoly V. and Rubtsova, Kira and Fischer, Aryeh and Meehan,
Richard T. and Gillis, Joann Z. and Kappler, John W. and Marrack,
Philippa},
title = {Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+
B-cell population is important for the development of autoimmunity},
journal = {Blood},
year = {2011},
volume = {118},
pages = {1305-1315},
number = {5},
abstract = {Females are more susceptible than males to many autoimmune diseases.
The processes causing this phenomenon are incompletely understood.
Here, we demonstrate that aged female mice acquire a previously uncharacterized
population of B cells that we call age-associated B cells (ABCs)
and that these cells express integrin X chain (CD11c). This unexpected
population also appears in young lupus-prone mice. On stimulation,
CD11c+ B cells, both from autoimmune-prone and healthy strains of
mice, secrete autoantibodies, and depletion of these cells in vivo
leads to reduction of autoreactive antibodies, suggesting that the
cells might have a direct role in the development of autoimmunity.
We have explored factors that contribute to appearance of ABCs and
demonstrated that signaling through Toll-like receptor 7 is crucial
for development of this B cell population. We were able to detect
a similar population of B cells in the peripheral blood of some elderly
women with autoimmune disease, suggesting that there may be parallels
between the creation of ABC-like cells between mice and humans.},
doi = {10.1182/blood-2011-01-331462},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/5/1305.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/5/1305}
}
@ARTICLE{Ruby2006,
author = {Ruby, Thomas and Whittaker, Catherine and Withers, David R. and Chelbi-Alix,
Mounira K. and Morin, Veronique and Oudin, Anne and Young, John R.
and Zoorob, Rima},
title = {Transcriptional Profiling Reveals a Possible Role for the Timing
of the Inflammatory Response in Determining Susceptibility to a Viral
Infection},
journal = {J. Virol.},
year = {2006},
volume = {80},
pages = {9207--9216},
number = {18},
month = sep,
abstract = {Using a novel cDNA microarray prepared from sources of actively responding
immune system cells, we have investigated the changes in gene expression
in the target tissue during the early stages of infection of neonatal
chickens with infectious bursal disease virus. Infections of two
lines of chickens previously documented as genetically resistant
and sensitive to infection were compared in order to ascertain early
differences in the response to infection that might provide clues
to the mechanism of differential genetic resistance. In addition
to major changes that could be explained by previously described
changes in infected tissue, some differences in gene expression on
infection, and differences between the two chicken lines, were observed
that led to a model for resistance in which a more rapid inflammatory
response and more-extensive p53-related induction of apoptosis in
the target B cells might limit viral replication and consequent pathology.
Ironically, the effect in the asymptomatic neonatal infection is
that more-severe B-cell depletion is seen in the more genetically
resistant chicken. Changes of expression of many chicken genes of
unknown function, indicating possible roles in the response to infection,
may aid in the functional annotation of these genes.},
url = {http://jvi.asm.org/cgi/content/abstract/80/18/9207}
}
@ARTICLE{Ruden2009,
author = {Ruden, Douglas M. and Chen, Lang and Possidente, Debra and Possidente,
Bernard and Rasouli, Parsa and Wang, Luan and Lu, Xiangyi and Garfinkel,
Mark D. and Hirsch, Helmut V.B. and Page, Grier P.},
title = {Genetical toxicogenomics in Drosophila identifies master-modulatory
loci that are regulated by developmental exposure to lead},
journal = {NeuroToxicology},
year = {2009},
volume = {30},
pages = {898--914},
number = {6},
month = nov,
abstract = {The genetics of gene expression in recombinant inbred lines (RILs)
can be mapped as expression quantitative trait loci (eQTLs). So-called
"genetical genomics" studies have identified locally acting eQTLs
(cis-eQTLs) for genes that show differences in steady-state RNA levels.
These studies have also identified distantly acting master-modulatory
trans-eQTLs that regulate tens or hundreds of transcripts (hotspots
or transbands). We expand on these studies by performing genetical
genomics experiments in two environments in order to identify trans-eQTL
that might be regulated by developmental exposure to the neurotoxin
lead. Flies from each of 75 RIL were raised from eggs to adults on
either control food (made with 250 [mu]M sodium acetate), or lead-treated
food (made with 250 [mu]M lead acetate, PbAc). RNA expression analyses
of whole adult male flies (5-10 days old) were performed with Affymetrix
DrosII whole genome arrays (18,952 probesets). Among the 1389 genes
with cis-eQTL, there were 405 genes unique to control flies and 544
genes unique to lead-treated ones (440 genes had the same cis-eQTLs
in both samples). There are 2396 genes with trans-eQTL which mapped
to 12 major transbands with greater than 95 genes. Permutation analyses
of the strain labels but not the expression data suggests that the
total number of eQTL and the number of transbands are more important
criteria for validation than the size of the transband. Two transbands,
one located on the 2nd chromosome and one on the 3rd chromosome,
co-regulate 33 lead-induced genes, many of which are involved in
neurodevelopmental processes. For these 33 genes, rather than allelic
variation at one locus exerting differential effects in two environments,
we found that variation at two different loci are required for optimal
effects on lead-induced expression.},
booktitle = {10th International Symposium on Neurobehavioral Methods and Effects
in Environmental and Occupational Health},
issn = {0161-813X},
keywords = {QTL, Expression profiling, Microarray, Heavy metals, Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/B6W81-4X5JSNW-1/2/c560752b2cf6cb26aad28ebd1a1c67eb}
}
@ARTICLE{Rudi2011,
author = {Rudi, Heidi and Sandve, Simen R. and Opseth, Lars M. and Larsen,
Arild and Rognli, Odd Arne},
title = {Identification of candidate genes important for frost tolerance in
Festuca pratensis Huds. by transcriptional profiling},
journal = {Plant Science},
year = {2011},
volume = {180},
pages = {78--85},
number = {1},
month = jan,
abstract = {Studies of differential gene expression between cold acclimated (CA)
and non-cold acclimated (NA) plants yield insight into how plants
prepare for cold stress at the transcriptional level. Furthermore
genes involved in the cold acclimation process are good candidate
loci for genetic variation in frost tolerance and winter survival.
In this study we combine different approaches to try to decode the
genetics of cold acclimation and frost tolerance in meadow fescue
(Festuca pratensis Huds). An EST library of cold acclimation responsive
genes was established by suppression subtractive hybridization (SSH),
and a microarray experiment was used to identify gene expression
differences between high and low frost tolerance genotypes in response
to cold acclimation. Many genes known to be involved in CA in other
species were confirmed to be involved in CA in F. pratensis, however,
18% of the ESTs did not show significant homology to any database
proteins. Seven genes were found to be differentially expressed (>2-fold)
between high and low frost tolerance genotypes. Two of these genes,
FpQM and FpTPT, represent interesting candidate genes for frost tolerance
in perennial forage grasses.},
booktitle = {Plant and Microbe Adaptation to Cold},
issn = {0168-9452},
keywords = {Festuca pratensis, Frost tolerance, Cold acclimation, Winter survival,
Perennial ryegrass, Expressed sequence tags},
url = {http://www.sciencedirect.com/science/article/pii/S0168945210002013}
}
@ARTICLE{Rudinskiy2009,
author = {Rudinskiy, Nikita and Kaneko, Yoshio A. and Beesen, Ayshe Ana and
Gokce, Ozgun and Régulier, Etienne and Déglon, Nicole and Luthi-Carter,
Ruth},
title = {Diminished hippocalcin expression in Huntington´s disease brain does
not account for increased striatal neuron vulnerability as assessed
in primary neurons},
journal = {Journal of Neurochemistry},
year = {2009},
volume = {111},
pages = {460--472},
number = {2},
abstract = {Abstract Hippocalcin is a neuronal calcium sensor protein previously
implicated in regulating neuronal viability and plasticity. Hippocalcin
is the most highly expressed neuronal calcium sensor in the medium
spiny striatal output neurons that degenerate selectively in Huntington’s
disease (HD). We have previously shown that decreased hippocalcin
expression occurs in parallel with the onset of disease phenotype
in mouse models of HD. Here we show by in situ hybridization histochemistry
that hippocalcin RNA is also diminished by 63% in human HD brain.
These findings lead us to hypothesize that diminished hippocalcin
expression might contribute to striatal neurodegeneration in HD.
We tested this hypothesis by assessing whether restoration of hippocalcin
expression would decrease striatal neurodegeneration in cellular
models of HD comprising primary striatal neurons exposed to mutant
huntingtin, the mitochondrial toxin 3-nitropropionic acid or an excitotoxic
concentration of glutamate. Counter to our hypothesis, hippocalcin
expression did not improve the survival of striatal neurons under
these conditions. Likewise, expression of hippocalcin together with
interactor proteins including the neuronal apoptosis inhibitory protein
did not increase the survival of striatal cells in cellular models
of HD. These results indicate that diminished hippocalcin expression
does not contribute to HD-related neurodegeneration.},
issn = {1471-4159},
keywords = {3-nitropropionic acid, calcium, excitotoxicity, hippocalcin, huntingtin,
Huntington’s disease},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2009.06344.x}
}
@ARTICLE{Rudkowska2010,
author = {Rudkowska, Iwona and Marcotte, Bruno and Pilon, Genevieve and Lavigne,
Charles and Marette, Andre and Vohl, Marie-Claude},
title = {Fish nutrients decrease expression levels of tumor necrosis factor-{alpha}
in cultured human macrophages},
journal = {Physiol Genomics},
year = {2010},
volume = {40},
pages = {189--194},
number = {3},
month = feb,
abstract = {Numerous studies have demonstrated the beneficial effects of fish
consumption on inflammatory markers. Until now, these beneficial
effects of fish consumption have been mostly linked to the omega-3
fatty acids (FA). The objective of the present study was to examine,
in vitro, whether expression levels of genes involved in the inflammatory
response differ in human macrophages incubated with casein hydrolysates
(CH) or fish protein hydrolysates (FPH) in the presence or absence
of omega-3 FA compared with omega-3 FA alone. Peripheral blood monocytes
differentiated into macrophages from 10 men were incubated in the
presence of omega-3 FA (10 {micro}M eicosapentaenoic acid and 5 {micro}M
docosahexaenoic acid) or CH or FPH (10, 100, 1,000 {micro}g) with
or without omega-3 FA for 48 h. Results demonstrate that expression
levels of tumor necrosis factor{alpha} (TNF{alpha}) had a tendency
to be lower after the addition of FPH alone or CH with omega-3 FA
compared with omega-3 FA treatment. Furthermore, the combination
of FPH and omega-3 FA synergistically decreased expression levels
of TNF{alpha} compared to treatment with omega-3 FA or FPH alone.
No difference on gene expression levels of interleukin-6 was observed
between treatments. In conclusion, these preliminary results suggest
that the anti-inflammatory effects of fish consumption can be explained
by a synergistic effect of the omega-3 FA with the protein components
of fish on TNF{alpha} expression and therefore contribute to the
beneficial effects of fish consumption. Hence, follow-up studies
should be performed to confirm the effects of a diet rich in FPH
and omega-3 FA on serum proinflammatory cytokine concentrations.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/40/3/189}
}
@ARTICLE{Rudolph2010,
author = {Rudolph, Michael C. and Monks, Jenifer and Burns, Valerie and Phistry,
Meridee and Marians, Russell and Foote, Monica R. and Bauman, Dale
E. and Anderson, Steven M. and Neville, Margaret C.},
title = {Sterol regulatory element binding protein and dietary lipid regulation
of fatty acid synthesis in the mammary epithelium},
journal = {Am J Physiol Endocrinol Metab},
year = {2010},
volume = {299},
pages = {E918--927},
number = {6},
month = dec,
abstract = {The lactating mammary gland synthesizes large amounts of triglyceride
from fatty acids derived from the blood and from de novo lipogenesis.
The latter is significantly increased at parturition and decreased
when additional dietary fatty acids become available. To begin to
understand the molecular regulation of de novo lipogenesis, we tested
the hypothesis that the transcription factor sterol regulatory element
binding factor (SREBF)-1c is a primary regulator of this system.
Expression of Srebf1c mRNA and six of its known target genes increased
[≥]2.5-fold at parturition. However, Srebf1c-null mice showed
only minor deficiencies in lipid synthesis during lactation, possibly
due to compensation by Srebf1a expression. To abrogate the function
of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial
cell-specific deletion of SREBF cleavage-activating protein (SCAP),
the SREBF escort protein. These dams showed a significant lactation
deficiency, and expression of mRNA for fatty acid synthase (Fasn),
insulin-induced gene 1 (Insig1), mitochondrial citrate transporter
(Slc25a1), and stearoyl-CoA desaturase 2 (Scd2) was reduced threefold
or more; however, the mRNA levels of acetyl-CoA carboxylase-1{alpha}
(Acaca) and ATP citrate lyase (Acly) were unchanged. Furthermore,
a 46% fat diet significantly decreased de novo fatty acid synthesis
and reduced the protein levels of ACACA, ACLY, and FASN significantly,
with no change in their mRNA levels. These data lead us to conclude
that two modes of regulation exist to control fatty acid synthesis
in the mammary gland of the lactating mouse: the well-known SREBF1
system and a novel mechanism that acts at the posttranscriptional
level in the presence of SCAP deletion and high-fat feeding to alter
enzyme protein.},
comment = {10.1152/ajpendo.00376.2010},
url = {http://ajpendo.physiology.org/cgi/content/abstract/299/6/E918}
}
@ARTICLE{Rudolph2011,
author = {Rudolph, Michael C. and Russell, Tanya D. and Webb, Patricia and
Neville, Margaret C. and Anderson, Steven M.},
title = {Prolactin-mediated regulation of lipid biosynthesis genes in vivo
in the lactating mammary epithelial cell},
journal = {Am J Physiol Endocrinol Metab},
year = {2011},
volume = {300},
pages = {E1059-1068},
number = {6},
abstract = {Prolactin (PRL) is known to play an essential role in mammary alveolar
proliferation in the pregnant mouse, but its role in lactation has
been more difficult to define. Genetic manipulations that alter expression
of the PRL receptor and its downstream signaling molecules resulted
in developmental defects that may directly or indirectly impact secretory
activation and lactation. To examine the in vivo role of PRL specifically
in lactation, bromocriptine (BrCr) was administered every 8 h to
lactating mice on the second day postpartum, resulting in an [~]95%
decrease in serum PRL levels. Although morphological changes in secretory
alveoli were slight, by 8 h of BrCr, pup growth was inhibited significantly.
Phosphorylated STAT5 fell to undetectable levels within 4 h. Decreased
milk protein gene expression, {beta}-casein, and -lactalbumin, was
observed after 8 h of treatment. To assess mammary-specific effects
on lipid synthesis genes, we isolated mammary epithelial cells (MECs)
depleted of mammary adipocytes. Expression of genes involved in glucose
uptake, glycolysis, pentose phosphate shunt, de novo synthesis of
fatty acids, and biosynthesis of triacylglycerides was decreased
up to 19-fold in MECs by just 8 h of BrCr treatment. Glands from
BrCr-treated mice showed a twofold reduction in intracellular cytoplasmic
lipid droplets and a reduction in cytosolic {beta}-casein. These
data demonstrate that PRL signaling regulates MEC-specific lipogenic
gene expression and that PRL signals coordinate the milk synthesis
and mammary epithelial cell survival during lactation in the mouse.},
doi = {10.1152/ajpendo.00083.2011},
eprint = {http://ajpendo.physiology.org/cgi/reprint/300/6/E1059.pdf},
url = {http://ajpendo.physiology.org/cgi/content/abstract/300/6/E1059}
}
@ARTICLE{Rue2011,
author = {Rue, Cary A. and Susta, Leonardo and Cornax, Ingrid and Brown, Corrie
C. and Kapczynski, Darrell R. and Suarez, David L. and King, Daniel
J. and Miller, Patti J. and Afonso, Claudio L.},
title = {Virulent Newcastle disease virus elicits a strong innate immune response
in chickens},
journal = {J. Gen. Virol.},
year = {2011},
volume = {92},
pages = {931--939},
number = {4},
month = apr,
abstract = {Newcastle disease virus (NDV) is an avian paramyxovirus that causes
significant economic losses to the poultry industry worldwide. There
is limited knowledge about the avian immune response to infection
with virulent NDVs, and how this response may contribute to disease.
In this study, pathogenesis and the transcriptional host response
of chickens to a virulent NDV strain that rapidly causes 100 % mortality
was characterized. Using microarrays, a strong transcriptional host
response was observed in spleens at early times after infection with
the induction of groups of genes involved in innate antiviral and
pro-inflammatory responses. There were multiple genes induced at
48 h post-infection including: type I and II interferons (IFNs),
several cytokines and chemokines, IFN effectors and inducible nitric
oxide synthase (iNOS). The increased transcription of nitric oxide
synthase was confirmed by immunohistochemistry for iNOS in spleens
and measured levels of nitric oxide in serum. In vitro experiments
showed strong induction of the key host response genes, alpha IFN,
beta interferon, and interleukin 1{beta} and interleukin 6, in splenic
leukocytes at 6 h post-infection in comparison to a non-virulent
NDV. The robust host response to virulent NDV, in conjunction with
severe pathological damage observed, is somewhat surprising considering
that all NDV encode a gene, V, which functions as a suppressor of
class I IFNs. Taken together, these results suggest that the host
response itself may contribute to the pathogenesis of this highly
virulent strain in chickens.},
comment = {10.1099/vir.0.025486-0},
url = {http://vir.sgmjournals.org/cgi/content/abstract/92/4/931}
}
@ARTICLE{Ruenwai2011,
author = {Ruenwai, Rawisara and Neiss, Andrea and Laoteng, Kobkul and Vongsangnak,
Wanwipa and Dalfard, Arastoo Badoei and Cheevadhanarak, Supapon and
Petranovic, Dina and Nielsen, Jens},
title = {Heterologous production of polyunsaturated fatty acids in Saccharomyces
cerevisiae causes a global transcriptional response resulting in
reduced proteasomal activity and increased oxidative stress},
journal = {Biotechnology Journal},
year = {2011},
volume = {6},
pages = {343--356},
number = {3},
abstract = {Abstract Due to their health benefits there is much interest in developing
microbial processes for efficient production of polyunsaturated fatty
acids (PUFAs). In this study we co-expressed Mucor rouxii Δ12- and
Δ6-desaturase genes in Saccharomyces cerevisiae, which resulted
in a yeast strain that accumulated linoleic acid and γ-linolenic
acid in the different lipid species. Additionally, the strain contained
higher levels of phospholipids and lower levels of ergosterol than
the reference strain. Integrated analysis of the transcriptome revealed
decreased expression of genes involved in ergosterol biosynthesis,
but more unexpectedly it also pointed towards attenuated activity
of the ubiquitin-proteasome system and a reduced oxidative stress
response. In vitro and in vivo measurements showed reduced levels
of all three proteasomal activities and also increased levels of
reactive oxidative species in the PUFA-producing strain. Overall
our results clearly show that PUFAs in yeast can be detrimental for
several key cellular pathways, such as the oxidative stress response
and proteasomal activity, suggesting that the membrane composition
is of vital importance for these processes.},
doi = {10.1002/biot.201000316},
issn = {1860-7314},
keywords = {Desaturase, Lipid biosynthesis, PUFAs, yeast, Stress response},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/biot.201000316}
}
@ARTICLE{Ruffel2008,
author = {Ruffel, Sandrine and Freixes, Sandra and Balzergue, Sandrine and
Tillard, Pascal and Jeudy, Christian and Martin-Magniette, Marie
Laure and van der Merwe, Margaretha J. and Kakar, Klementina and
Gouzy, Jerome and Fernie, Alisdair R. and Udvardi, Michael and Salon,
Christophe and Gojon, Alain and Lepetit, Marc},
title = {Systemic Signaling of the Plant Nitrogen Status Triggers Specific
Transcriptome Responses Depending on the Nitrogen Source in Medicago
truncatula},
journal = {Plant Physiology},
year = {2008},
volume = {146},
pages = {2020--2035},
number = {4},
month = apr,
abstract = {Legumes can acquire nitrogen (N) from NO3-, NH4+, and N2 (through
symbiosis with Rhizobium bacteria); however, the mechanisms by which
uptake and assimilation of these N forms are coordinately regulated
to match the N demand of the plant are currently unknown. Here, we
find by use of the split-root approach in Medicago truncatula plants
that NO3- uptake, NH4+ uptake, and N2 fixation are under general
control by systemic signaling of plant N status. Indeed, irrespective
of the nature of the N source, N acquisition by one side of the root
system is repressed by high N supply to the other side. Transcriptome
analysis facilitated the identification of over 3,000 genes that
were regulated by systemic signaling of the plant N status. However,
detailed scrutiny of the data revealed that the observation of differential
gene expression was highly dependent on the N source. Localized N
starvation results, in the unstarved roots of the same plant, in
a strong compensatory up-regulation of NO3- uptake but not of either
NH4+ uptake or N2 fixation. This indicates that the three N acquisition
pathways do not always respond similarly to a change in plant N status.
When taken together, these data indicate that although systemic signals
of N status control root N acquisition, the regulatory gene networks
targeted by these signals, as well as the functional response of
the N acquisition systems, are predominantly determined by the nature
of the N source.},
url = {http://www.plantphysiol.org/cgi/content/abstract/146/4/2020}
}
@ARTICLE{Ruger-Herreros2011,
author = {Ruger-Herreros, Carmen and Rodriguez-Romero, Julio and Fernandez-Barranco,
Raul and Olmedo, Maria and Fischer, Reinhard and Corrochano, Luis
M. and Canovas, David},
title = {Regulation of Conidiation by Light in Aspergillus nidulans},
journal = {Genetics},
year = {2011},
volume = {188},
pages = {809-822},
number = {4},
abstract = {Light regulates several aspects of the biology of many organisms,
including the balance between asexual and sexual development in some
fungi. To understand how light regulates fungal development at the
molecular level we have used Aspergillus nidulans as a model. We
have performed a genome-wide expression analysis that has allowed
us to identify >400 genes upregulated and >100 genes downregulated
by light in developmentally competent mycelium. Among the upregulated
genes were genes required for the regulation of asexual development,
one of the major biological responses to light in A. nidulans, which
is a pathway controlled by the master regulatory gene brlA. The expression
of brlA, like conidiation, is induced by light. A detailed analysis
of brlA light regulation revealed increased expression after short
exposures with a maximum after 60 min of light followed by photoadaptation
with longer light exposures. In addition to brlA, genes flbA-C and
fluG are also light regulated, and flbA-C are required for the correct
light-dependent regulation of the upstream regulator fluG. We have
found that light induction of brlA required the photoreceptor complex
composed of a phytochrome FphA, and the white-collar homologs LreA
and LreB, and the fluffy genes flbA-C. We propose that the activation
of regulatory genes by light is the key event in the activation of
asexual development by light in A. nidulans.},
doi = {10.1534/genetics.111.130096},
eprint = {http://www.genetics.org/cgi/reprint/188/4/809.pdf},
url = {http://www.genetics.org/cgi/content/abstract/188/4/809}
}
@ARTICLE{Ruggeri2008,
author = {Ruggeri, B. and Ubaldi, M. and Lourdusamy, A. and Soverchia, L. and
Ciccocioppo, R. and Hardiman, G. and Baker, M.E. and Palermo, F.
and Polzonetti-Magni, A.M.},
title = {Variation of the genetic expression pattern after exposure to estradiol-17[beta]
and 4-nonylphenol in male zebrafish (Danio rerio)},
journal = {General and Comparative Endocrinology},
year = {2008},
volume = {158},
pages = {138--144},
number = {1},
month = aug,
abstract = {There is much concern about the increasing presence in the environment
of synthetic chemicals that are able to disrupt the endocrine system.
Among these compounds, 4-nonylphenol (4-NP) is one of the most studied
xenoestrogens, due to its widespread accumulation in water sediment
and consequent presence in fatty acid of aquatic organisms. Here,
we have used a zebrafish microarray representing 16,399 genes to
study the effects of 4-NP and estradiol-17[beta] (E2) in adult male
zebrafish in order to elucidate the mechanism of action of 4-NP compared
with that of E2. The microarray results showed that both 4-NP and
E2 induced a strong expression of vitellogenin (VTG), the sex related
precursor of the yolk proteins in oviparous vertebrates. Both treatments
induced elevated protein turnover upregulating genes involved in
proteolysis and those that are constituents of the ribosome. Many
genes regulated by 4-NP and E2 are involved in energy metabolism,
oxidative stress defense mechanisms, xenobiotic metabolism, and lipid
metabolism. A different pattern of expression in the two treatments
was found for genes involved in oxidative stress, since E2 seems
to induce the mechanism of detoxification, while 4-NP seems to inhibit
this protective mechanism of the cell. Overall, these findings demonstrate
that the microarray approach can contribute significantly to the
understanding of expression patterns induced by E2 and 4-NP in male
zebrafish. The results also demonstrate that 4-NP is able to act
through an alternative pattern to that of estradiol-17[beta], modulating
the expression of the same genes in a different manner.},
issn = {0016-6480},
keywords = {Zebrafish, 4-Nonyphenol, Estradiol-17[beta], Microarray},
url = {http://www.sciencedirect.com/science/article/B6WG0-4SMDYXN-2/2/cd4bcfe8deb535a9f0947d51f88377ba}
}
@ARTICLE{Ruijter2005,
author = {de Ruijter, Annemieke J.M. and Meinsma, Rutger J. and Bosma, Peter
and Kemp, Stephan and Caron, Huib N. and van Kuilenburg, André B.P.},
title = {Gene expression profiling in response to the histone deacetylase
inhibitor BL1521 in neuroblastoma},
journal = {Experimental Cell Research},
year = {2005},
volume = {309},
pages = {451--467},
number = {2},
month = oct,
abstract = {Neuroblastoma is a childhood tumor with a poor survival in advanced
stage disease despite intensive chemotherapeutic regimes. The new
histone deacetylase (HDAC) inhibitor BL1521 has shown promising results
in neuroblastoma. Inhibition of HDAC resulted in a decrease in proliferation
and metabolic activity, induction of apoptosis and differentiation
of neuroblastoma cells. In order to elucidate the mechanism mediating
the effects of BL1521 on neuroblastoma cells, we investigated the
gene expression profile of an MYCN single copy (SKNAS) and an MYCN
amplified (IMR32) neuroblastoma cell line after treatment with BL1521
using the Affymetrix oligonucleotide array U133A. An altered expression
of 255 genes was observed in both neuroblastoma cell lines. The majority
of these genes were involved in gene expression, cellular metabolism,
and cell signaling. We observed changes in the expression of vital
genes belonging to the cell cycle (cyclin D1 and CDK4) and apoptosis
(BNIP3, BID, and BCL2) pathway in response to BL1521. The expression
of 37 genes was altered by both BL1521 and Trichostatin A, which
could indicate a common gene set regulated by different HDAC inhibitors.
BL1521 treatment changed the expression of a number of MYCN-associated
genes. Several genes in the Wnt and the Delta/Notch pathways were
changed in response to BL1521 treatment, suggesting that BL1521 is
able to induce the differentiation of neuroblastoma cells into a
more mature phenotype.},
issn = {0014-4827},
keywords = {BL1521, Histone deacetylase inhibitor, TSA, Oligonucleotide array,
Neuroblastoma, Differentiation, Apoptosis, Cell cycle},
url = {http://www.sciencedirect.com/science/article/B6WFC-4GTVYTY-2/2/a102a8130a661f6ccfd19169e7ac8cf3}
}
@ARTICLE{Ruijter2009,
author = {Ruijter, J. M. and Ramakers, C. and Hoogaars, W. M. H. and Karlen,
Y. and Bakker, O. and van den Hoff, M. J. B. and Moorman, A. F. M.},
title = {Amplification efficiency: linking baseline and bias in the analysis
of quantitative PCR data},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {e45--},
number = {6},
month = apr,
abstract = {Despite the central role of quantitative PCR (qPCR) in the quantification
of mRNA transcripts, most analyses of qPCR data are still delegated
to the software that comes with the qPCR apparatus. This is especially
true for the handling of the fluorescence baseline. This article
shows that baseline estimation errors are directly reflected in the
observed PCR efficiency values and are thus propagated exponentially
in the estimated starting concentrations as well as fold-difference'
results. Because of the unknown origin and kinetics of the baseline
fluorescence, the fluorescence values monitored in the initial cycles
of the PCR reaction cannot be used to estimate a useful baseline
value. An algorithm that estimates the baseline by reconstructing
the log-linear phase downward from the early plateau phase of the
PCR reaction was developed and shown to lead to very reproducible
PCR efficiency values. PCR efficiency values were determined per
sample by fitting a regression line to a subset of data points in
the log-linear phase. The variability, as well as the bias, in qPCR
results was significantly reduced when the mean of these PCR efficiencies
per amplicon was used in the calculation of an estimate of the starting
concentration per sample.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/6/e45}
}
@ARTICLE{Ruiz2008,
author = {Ruiz, Sergio and Castro-Castro, Antonio and Bustelo, Xose R.},
title = {CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing
Vav1 and Rac1 Downstream Signaling},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {5554--5566},
number = {9},
month = feb,
abstract = {CD147 is a transmembrane protein that plays crucial roles in the development
and function of the reproductive, visual, and nervous systems. CD147
also exerts positive and negative actions in T-cells by still obscure
mechanisms. In this study, we have analyzed the expression, localization,
and function of CD147 during T-cell receptor signaling responses.
We show here that CD147 is an integral component of the T-cell immune
synapse and that its overexpression leads to the inhibition of NF-AT
(nuclear factor of activated T-cells) activity induced by Vav1, a
Rac1 exchange factor. This inhibitory activity is mediated by the
CD147 intracellular tail and is totally independent of its extracellular
or transmembrane regions. The molecular dissection of the influence
of CD147 on the Vav1 pathway indicates that its inhibitory action
takes place downstream of Vav1 and Rac1 but upstream of the serine/threonine
kinases JNK and Pak1. The interference of CD147 with these pathways
is highly specific because the overexpression of CD147 does not affect
the activity of other GDP/GTP exchange factors or the stimulation
of the ERK cascade. Finally, we show that the CD147 knockdown in
Jurkat cells promotes higher levels of NF-AT stimulation and Pak1
phosphorylation upon T-cell receptor cross-linking. Instead, the
lack of CD147 does not affect other signaling cascades that participate
in the same cellular response. Taken together, these results indicate
that CD147, via the selective inhibition of specific downstream elements
of the Vav1/Rac1 route, contributes to the negative regulation of
T-cell responses.},
url = {http://www.jbc.org/cgi/content/abstract/283/9/5554}
}
@ARTICLE{Ruiz2007,
author = {Ruiz, Sergio and Santos, Eugenio and Bustelo, Xose R.},
title = {RasGRF2, a Guanosine Nucleotide Exchange Factor for Ras GTPases,
Participates in T-Cell Signaling Responses},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {8127--8142},
number = {23},
month = dec,
abstract = {The Ras pathway is critical for the development and function of T
lymphocytes. The stimulation of this GTPase in T cells occurs primarily
through the Vav1- and phospholipase C-{gamma}1-dependent activation
of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor.
Here, we show that a second exchange factor, RasGRF2, also participates
in T-cell signaling. RasGRF2 is expressed in T cells, translocates
to immune synapses, activates Ras, and stimulates the transcriptional
factor NF-AT (nuclear factor of activated T cells) through Ras- and
phospholipase C-{gamma}1-dependent routes. T-cell receptor-, Vav1-,
and Ca2+-elicited pathways synergize with RasGRF2 for NF-AT stimulation.
The analysis of RasGRF2-deficient mice indicates that this protein
is required for the induction of bona fide NF-AT targets such as
the cytokines tumor necrosis factor alpha and interleukin 2, while
it plays minor roles in Ras activation itself. The comparison of
lymphocytes from Vav1-/-, Rasgrf2-/-, and Vav1-/-; Rasgrf2-/- mice
demonstrates that the RasGRF2 pathway cooperates with the Vav1/RasGRP1
route in the blasting transformation and proliferation of mature
T cells. These results identify RasGRF2 as an additional component
of the signaling machinery involved in T-cell receptor- and NF-AT-mediated
immune responses.},
url = {http://mcb.asm.org/cgi/content/abstract/27/23/8127}
}
@ARTICLE{Ruiz-Perez2008,
author = {Ruiz-Perez, B. and Dowie, T. and Gee, R. and Isom, P. and Manzo,
M. and Skokanova, E.},
title = {Transscleral Delivery of a 12.4 kDa Protein by Ocular Iontophoresis},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {1813--},
number = {5},
month = apr,
abstract = {PurposeTo test delivery of cytochrome C, a 12.4 kDa protein, into
the eye by iontophoresis. MethodsFor in vitro testing, anodal iontophoresis
was performed using a two chamber Ussing apparatus. 40 mg/mL of cytochrome
C in H2O was used in the donor chamber and phosphate buffered saline
solution was used in the receptor chamber. Visual inspection and
the Agilent Bioanalyzer(R) were used to detect the cytochrome C.
For ex vivo testing, cadaver adult rabbit eyes were dosed with 40
mg/mL of cytochrome C using the EyeGate II device for 15 and 20 mA*mins.
Tissues were harvested and a qualitative measurement of cytochrome
C was obtained via its chromophore on a UV spectrophotometer at 220
nM. For in vivo testing, four rabbits were dosed with 40 mg/mL of
cytochrome C using the EyeGate II device; two rabbits received 15
mA*mins (anodal iontophoresis) while the two control rabbits received
0 mA*mins (passive). Eyes from control and treatment groups were
harvested immediately after dosing and 2 hours post-dosing. ResultsIn
vitro experiments showed a slight red coloring of the cytochrome
C in the passive receptor chambers; red coloring was observed to
be more intense in receptor chambers after anodal iontophoresis was
applied. 3% of the cytochrome C was delivered by iontophoresis while
only 0.27% of the protein was delivered passively. Additionally,
after anodal iontophoresis in cadaver eyes, cytochrome C was detected
in all ocular tissues harvested. Both the 15 and 20 mA/mins treated
eyes showed similar distribution of cytochrome C between tissues
with the exception of the conjunctiva which showed slightly higher
levels at 20 mA/mins. Moreover, in the in vivo rabbit model, the
red coloring of the cytochrome C was clearly observed within each
iontophoretically treated eye while no red color was observed in
the passively treated eyes. ConclusionsThese data indicate successful
transscleral delivery of the 12.4 kDa cytochrome C protein. Additionally,
in vitro results show an 11.2 fold increase in iontophoretic delivery
over passive delivery alone.},
url = {http://abstracts.iovs.org/cgi/content/abstract/49/5/1813}
}
@ARTICLE{Rujkijyanont2007,
author = {Rujkijyanont, Piya and Beyene, Joseph and Wei, Kuiru and Khan, Fahad
and Dror, Yigal},
title = {Leukaemia-related gene expression in bone marrow cells from patients
with the preleukaemic disorder Shwachman–Diamond syndrome},
journal = {British Journal of Haematology},
year = {2007},
volume = {137},
pages = {537--544},
number = {6},
abstract = {Summary Shwachman–Diamond syndrome (SDS) is an inherited bone marrow
failure disorder with cytopenia and a high propensity for myelodysplastic
syndrome (MDS) and leukaemia, particularly acute myeloid leukaemia.
The mechanism of leukaemogenesis in SDS is unknown. In accordance
to the multi-hit theory of carcinogenesis, it is likely that several
molecular and cellular hits occur before MDS/leukaemia become apparent.
This study used oligonucleotide microarray to identify gene expression
patterns, which were shown to be associated with leukaemogenesis,
in marrow mononuclear cells of nine SDS patients without overt transformation
compared to healthy controls. Among 154 known leukaemia-related genes,
several oncogenes were found to be upregulated, including LARG, TAL1
and MLL, and of several tumour suppressor genes were downregulated,
including DLEU1, RUNX1, FANCD2 and DKC1. Real time polymerase chain
reaction confirmed statistically higher expression of LARG and TAL1
in SDS marrows. We conclude that SDS marrow mononuclear cells exhibit
abnormal gene expression patterns, which might result in continuous
stimulation favouring evolution or progression of malignant clones.
Additional molecular and cytogenetic events are probably necessary
for the malignant process to be irreversible and complete.},
issn = {1365-2141},
keywords = {Shwachman–Diamond syndrome, SBDS, Leukaemia, microarray, gene expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2007.06608.x}
}
@ARTICLE{Rul2011,
author = {Rul, Francoise and Ben-Yahia, Leila and Chegdani, Fatima and Wrzosek,
Laura and Thomas, Stephane and Noordine, Marie-Louise and Gitton,
Christophe and Cherbuy, Claire and Langella, Philippe and Thomas,
Muriel},
title = {Impact of the Metabolic Activity of Streptococcus thermophilus on
the Colon Epithelium of Gnotobiotic Rats},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {10288--10296},
number = {12},
month = mar,
abstract = {The thermophilic lactic acid bacterium Streptococcus thermophilus
is widely and traditionally used in the dairy industry. Despite the
vast level of consumption of S. thermophilus through yogurt or probiotic
functional food, very few data are available about its physiology
in the gastrointestinal tract (GIT). The objective of the present
work was to explore both the metabolic activity and host response
of S. thermophilus in vivo. Our study profiles the protein expression
of S. thermophilus after its adaptation to the GIT of gnotobiotic
rats and describes the impact of S. thermophilus colonization on
the colonic epithelium. S. thermophilus colonized progressively the
GIT of germ-free rats to reach a stable population in 30 days (108
cfu/g of feces). This progressive colonization suggested that S.
thermophilus undergoes an adaptation process within GIT. Indeed,
we showed that the main response of S. thermophilus in the rat's
GIT was the massive induction of the glycolysis pathway, leading
to formation of lactate in the cecum. At the level of the colonic
epithelium, the abundance of monocarboxylic acid transporter mRNAs
(SLC16A1 and SLC5A8) and a protein involved in the cell cycle arrest
(p27kip1) increased in the presence of S. thermophilus compared with
germ-free rats. Based on different mono-associated rats harboring
two different strains of S. thermophilus (LMD-9 or LMG18311) or weak
lactate-producing commensal bacteria (Bacteroides thetaiotaomicron
and Ruminococcus gnavus), we propose that lactate could be a signal
produced by S. thermophilus and modulating the colon epithelium.},
comment = {10.1074/jbc.M110.168666},
url = {http://www.jbc.org/cgi/content/abstract/286/12/10288}
}
@ARTICLE{Rull2008,
author = {Rull, K. and Hallast, P. and Uuskula, L. and Jackson, J. and Punab,
M. and Salumets, A. and Campbell, R.K. and Laan, M.},
title = {Fine-scale quantification of HCG beta gene transcription in human
trophoblastic and non-malignant non-trophoblastic tissues},
journal = {Mol. Hum. Reprod.},
year = {2008},
volume = {14},
pages = {23--31},
number = {1},
month = jan,
abstract = {Human chorionic gonadotropin (HCG) is produced by syncytiotrophoblast
of placenta. It delays the apoptosis of corpus luteum and functions
in implantation. Its possible role in male reproduction has been
raised. HCG beta subunit is encoded by CGB, CGB5, CGB7 and CGB8 genes
located at 19q13.3 in a common genome cluster with beta subunit non-coding
CGB1 and CGB2. We conducted a sensitive quantification and comparison
of CGB gene expression in human trophoblastic (blastocysts, n = 6;
normal/failed pregnancy, n = 51) and non-malignant non-trophoblastic
tissues (15 different tissue types, samples n = 241), by real-time
RT-PCR. We showed a wide transcriptional window of CGB genes in normal
pregnancy, a significant reduction in recurrent miscarriages, and
a high expression (especially CGB1/CGB2) in ectopic and molar pregnancies.
Expression was several orders of magnitude lower in the non-placental
tissues, with the highest CGB levels being seen in testis, prostate,
thymus, skeletal muscle and lung samples. The contribution of CGB1/CGB2
to the summarized expression of six CGB genes was not proportional
to their gene dosage: 1/1000 to 1/10 000. An interesting exception
was the testis exhibiting a much higher CGB1/CGB2 to total CGB mRNA
ratio of [~]one-third, corresponding to gene dosage. In conclusion,
the expressional profile of CGB genes, activated already in blastocyst
stage, is associated with the status of pregnancy. The presence of
CGB transcripts in testes, and in particular CGB1/CGB2 transcripts,
may indicate a role in male reproductive tract.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/14/1/23}
}
@ARTICLE{Rumbo2004,
author = {Rumbo, Martin and Sierro, Frédéric and Debard, Nathalie and Kraehenbuhl,
Jean-Pierre and Finke, Daniela},
title = {Lymphotoxin [beta] receptor signaling induces the chemokine CCL20
in intestinal epithelium},
journal = {Gastroenterology},
year = {2004},
volume = {127},
pages = {213--223},
number = {1},
month = jul,
abstract = {: The follicle-associated epithelium (FAE) that overlies Peyer's patches
(PPs) exhibits distinct features compared with the adjacent villus
epithelium. Besides the presence of antigen-sampling membranous M
cells and the down-regulation of digestive functions, it constitutively
expresses the chemokine CCL20. The mechanisms that induce FAE differentiation
and CCL20 expression are poorly understood. The aim of this work
was to test whether lymphotoxin [beta] receptor signaling (LT[beta]R),
which plays a central role in PPs' organogenesis, mediates CCL20
gene expression in intestinal epithelial cells. : CCL20, lymphotoxin
[beta] (LT[beta]) and LT[beta]R expression were monitored during
embryonic development by in situ hybridization of mouse intestine.
The human intestinal epithelial cell line T84 was used to study CCL20
expression following LT[alpha]1/[beta]2 stimulation. In vivo CCL20
expression following agonistic anti-LT[beta]R antibody treatment
was studied by laser microdissection and quantitative RT-PCR. : CCL20
was expressed in the FAE before birth at the time when the first
hematopoietic CD4+CD3- appeared in the PP anlage. LT[beta]R was expressed
in the epithelium during PP organogenesis, making it a putative target
for LT[alpha]1[beta]2signals. In vitro, CCL20 was induced in T84
cells upon LT[beta]R signaling, either using an agonistic ligand
or anti-LT[beta] receptor agonistic antibody. LT[alpha]1[beta]2-induced
CCL20 expression was found to be NF-[kappa]B dependent. LT[beta]R
signaling up-regulated CCL20 expression in the small intestinal epithelium
in vivo. : Our results show that LT[beta]R signaling induces CCL20
expression in intestinal epithelial cells, suggesting that this pathway
triggers constitutive production of CCL20 in the FAE.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4CRXPYD-1D/2/7bf2f4287463edffbc8673b1a8ceb148}
}
@ARTICLE{Rumfelt2006,
author = {Rumfelt, Lynn L. and Zhou, Yan and Rowley, Benjamin M. and Shinton,
Susan A. and Hardy, Richard R.},
title = {Lineage specification and plasticity in CD19- early B cell precursors},
journal = {J. Exp. Med.},
year = {2006},
volume = {203},
pages = {675--687},
number = {3},
month = mar,
abstract = {We describe here three CD19- B cell precursor populations in mouse
bone marrow identified using 12-color flow cytometry. Cell transfer
experiments indicate lineage potentials consistent with multilineage
progenitor (MLP), common lymphoid progenitor (CLP), and B lineage-restricted
pre-pro-B (Fr. A), respectively. However, single cell in vitro assays
reveal lineage plasticity: lymphoid/myeloid lineage potential for
CLP and B/T lineage potential for Fr. A. Despite myeloid potential,
recombination activating gene 2 reporter activation is first detected
at low levels in most MLP cells, with 95% of CLPs showing 10-fold
increased levels. Furthermore, single cell analysis shows that half
of CLP and 90% of Fr. A cells contain heavy chain DJ rearrangements.
These data, together with expression profiles of lineage-specific
genes, demonstrate progressive acquisition of B lineage potential
and support an asynchronous view of early B cell development, in
which B lineage specification initiates in the MLP/CLP stage, whereas
myeloid potential is not lost until the pre-pro-B (Fr. A) stage,
and B/T lymphoid plasticity persists until the CD19+ pro-B stage.
Thus, MLP, CLP, and Fr. A represent progressively B lineage-specified
stages in development, before the CD19+ B lineage-committed pro-B
stage.},
url = {http://jem.rupress.org/cgi/content/abstract/203/3/675}
}
@ARTICLE{Ruminy2007,
author = {Ruminy, Philippe and Jardin, Fabrice and Penther, Dominique and Picquenot,
Jean-Michel and Parmentier, Françoise and Buchonnet, Gérard and
Bertrand, Philippe and Tilly, Hervé and Bastard, Christian},
title = {Recurrent disruption of the Iμ splice donor site in t(14;18) positive
lymphomas : A potential molecular basis for aberrant downstream class
switch recombination},
journal = {Genes Chromosom. Cancer},
year = {2007},
volume = {46},
pages = {735--744},
number = {8},
abstract = {Abstract 10.1002/gcc.20453.abs t(14;18) positive lymphomas are mature
germinal center B-cell neoplasms. In agreement with this cellular
origin, most have somatically mutated immunoglobulin variable genes
and the IGH@ locus has almost always been reorganized by class switch
recombination (CSR). However, contrasting with normal B-cells, a
majority of cases still express an IgM while the constant genes are
normally rearranged only on the non-productive allele. Concurrently,
aberrant intra-allelic junctions involving downstream switch regions,
with a lack of engagement of the switch μ (Sμ), often accumulate
on the functional alleles, suggesting some recurrent CSR perturbation
during the onset of the disease. To clarify these surprising observations,
we addressed the accessibility of the Sμ to the CSR machinery in
a large series of patients by characterizing the mutations that are
expected to accumulate at this place upon CSR activation. Our data
indicate that the Sμ is mutated in a large majority of cases, often
on both alleles, indicating that these cells usually reach a differentiation
stage where CSR is activated and where this region remains accessible.
Interestingly, we also identified a significant cluster of mutations
at the splicing donor site of the first exon of the Sμ germline
transcripts, on the functional allele. This location suggests a possible
relation with CSR perturbations in lymphoma and the clustering points
to a probable mechanism of selection. In conclusion, our data suggest
that an acquired mutation at the splicing donor site of the Sμ transcripts
may participate in the selection of lymphoma cells and play a significant
role during the onset of the disease. © 2007 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20453}
}
@ARTICLE{Rund2011,
author = {Rund, Samuel S. C. and Hou, Tim Y. and Ward, Sarah M. and Collins,
Frank H. and Duffield, Giles E.},
title = {PNAS Plus: Genome-wide profiling of diel and circadian gene expression
in the malaria vector Anopheles gambiae},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {E421-430},
number = {32},
abstract = {Anopheles gambiae, the primary African vector of malaria parasites,
exhibits numerous rhythmic behaviors including flight activity, swarming,
mating, host seeking, egg laying, and sugar feeding. However, little
work has been performed to elucidate the molecular basis for these
daily rhythms. To study how gene expression is regulated globally
by diel and circadian mechanisms, we have undertaken a DNA microarray
analysis of An. gambiae under light/dark cycle (LD) and constant
dark (DD) conditions. Adult mated, non-blood-fed female mosquitoes
were collected every 4 h for 48 h, and samples were processed with
DNA microarrays. Using a cosine wave-fitting algorithm, we identified
1,293 and 600 rhythmic genes with a period length of 20-28 h in the
head and body, respectively, under LD conditions, representing 9.7
and 4.5% of the An. gambiae gene set. A majority of these genes was
specific to heads or bodies. Examination of mosquitoes under DD conditions
revealed that rhythmic programming of the transcriptome is dependent
on an interaction between the endogenous clock and extrinsic regulation
by the LD cycle. A subset of genes, including the canonical clock
components, was expressed rhythmically under both environmental conditions.
A majority of genes had peak expression clustered around the day/night
transitions, anticipating dawn and dusk. Genes cover diverse biological
processes such as transcription/translation, metabolism, detoxification,
olfaction, vision, cuticle regulation, and immunity, and include
rate-limiting steps in the pathways. This study highlights the fundamental
roles that both the circadian clock and light play in the physiology
of this important insect vector and suggests targets for intervention.},
doi = {10.1073/pnas.1100584108},
eprint = {http://www.pnas.org/cgi/reprint/108/32/E421.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/32/E421}
}
@ARTICLE{Rundle2008,
author = {Rundle, Charles H. and Strong, Donna D. and Chen, Shin-Tai and Linkhart,
Thomas A. and Sheng, Matilda H.-C. and Wergedal, Jon E. and Lau,
K.-H. William and Baylink, David J.},
title = {Retroviral-based gene therapy with cyclooxygenase-2 promotes the
union of bony callus tissues and accelerates fracture healing in
the rat},
journal = {J. Gene Med.},
year = {2008},
volume = {10},
pages = {229--241},
number = {3},
abstract = {Abstract 10.1002/jgm.1148.abs Background An in vivo gene therapy strategy
was developed to accelerate bone fracture repair. Methods Direct
injection of a murine leukemia virus-based vector targeted transgene
expression to the proliferating periosteal cells arising shortly
after fracture. Cyclooxygenase-2 (Cox-2) was selected because the
transgene for its prostaglandin products that promote angiogenesis,
bone formation and bone resorption, are all required for fracture
healing. The human (h) Cox-2 transgene was modified to remove AU-rich
elements in the 3′-untranslated region and to improve protein translation.
Results In vitro studies revealed robust and sustained Cox-2 protein
expression, prostaglandin E2 and alkaline phosphatase production
in rat bone marrow stromal cells and osteoblasts transgenic for the
hCox-2 gene. In vivo studies in the rat femur fracture revealed that
Cox-2 transgene expression produced bony union of the fracture by
21 days post-fracture, a time when cartilage persisted within the
fracture tissues of control animals and approximately 1 week earlier
than the healing normally observed in this model. None of the ectopic
bone formation associated with bone morphogenetic protein gene therapy
was observed. Conclusions This study represents the first demonstration
that a single local application of a retroviral vector expressing
a single osteoinductive transgene consistently accelerated fracture
repair. Copyright © 2007 John Wiley & Sons, Ltd.},
issn = {1521-2254},
keywords = {bone, cyclooxygenase-2, fracture healing, gene therapy, prostagland-
ins, retroviral vectors},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jgm.1148}
}
@ARTICLE{Rundle2006,
author = {Rundle, Charles H. and Wang, Hali and Yu, Hongrun and Chadwick, Robert
B. and Davis, Emile I. and Wergedal, Jon E. and Lau, K.-H. William
and Mohan, Subburaman and Ryaby, James T. and Baylink, David J.},
title = {Microarray analysis of gene expression during the inflammation and
endochondral bone formation stages of rat femur fracture repair},
journal = {Bone},
year = {2006},
volume = {38},
pages = {521--529},
number = {4},
month = apr,
abstract = {Microarray analysis of gene expression was performed in the healing
femur fractures of 13-week-old male rats during the inflammatory
stage of repair, at 3 days post-fracture, and the endochondral bone
formation stage of repair, at 11 days post-fracture. Multiple replicate
pairs of fracture tissues paired with unfractured tissues, and unfractured
control bones that had the stabilizing K-wire were introduced. This
approach normalized the marrow contributions to the RNA repertoire.
We identified 6555 genes with significant changes in expression in
fracture tissues at 3 days and 11 days healing. The repertoire of
growth factor genes expressed was also surprisingly restricted at
both post-fracture intervals. The large number of Expressed Sequence
Tags (ESTs) expressed at both post-fracture times indicates that
several molecular pathways yet to be identified regulate fracture
repair. The number of genes expressed during immune responses and
inflammatory processes was restricted with higher expression largely
during the early post-fracture analysis. Several of the genes identified
in this study have been associated with regulation of cell and extracellular
matrix interactions during scarless healing of fetal skin wounds.
These observations suggest that these genes might also regulate the
scarless healing characteristic of bone regeneration by similar mechanisms.},
issn = {8756-3282},
keywords = {Fracture healing, Microarray, Inflammation, Endochondral, Scarless},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4HNYMMX-1/2/bb40ab4d2fdb1f99e2fb5d8e48faf34d}
}
@ARTICLE{Runne2007,
author = {Runne, Heike and Kuhn, Alexandre and Wild, Edward J. and Pratyaksha,
Wirahpati and Kristiansen, Mark and Isaacs, Jeremy D. and Regulier,
Etienne and Delorenzi, Mauro and Tabrizi, Sarah J. and Luthi-Carter,
Ruth},
title = {Analysis of potential transcriptomic biomarkers for Huntington's
disease in peripheral blood},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {14424--14429},
number = {36},
month = sep,
abstract = {Highly quantitative biomarkers of neurodegenerative disease remain
an important need in the urgent quest for disease-modifying therapies.
For Huntington's disease (HD), a genetic test is available (trait
marker), but necessary state markers are still in development. In
this report, we describe a large battery of transcriptomic tests
explored as state biomarker candidates. In an attempt to exploit
the known neuroinflammatory and transcriptional perturbations of
disease, we measured relevant mRNAs in peripheral blood cells. The
performance of these potential markers was weak overall, with only
one mRNA, immediate early response 3 (IER3), showing a modest but
significant increase of 32% in HD samples compared with controls.
No statistically significant differences were found for any other
mRNAs tested, including a panel of 12 RNA biomarkers identified in
a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then
F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, et al. (2005)
Proc Natl Acad Sci USA 102:11023-11028]. The present results may
nonetheless inform the future design and testing of HD biomarker
strategies.},
url = {http://www.pnas.org/cgi/content/abstract/104/36/14424}
}
@ARTICLE{Runne2008,
author = {Runne, Heike and Regulier, Etienne and Kuhn, Alexandre and Zala,
Diana and Gokce, Ozgun and Perrin, Valerie and Sick, Beate and Aebischer,
Patrick and Deglon, Nicole and Luthi-Carter, Ruth},
title = {Dysregulation of Gene Expression in Primary Neuron Models of Huntington's
Disease Shows That Polyglutamine-Related Effects on the Striatal
Transcriptome May Not Be Dependent on Brain Circuitry},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {9723--9731},
number = {39},
month = sep,
abstract = {Gene expression changes are a hallmark of the neuropathology of Huntington's
disease (HD), but the exact molecular mechanisms of this effect remain
uncertain. Here, we report that in vitro models of disease comprised
of primary striatal neurons expressing N-terminal fragments of mutant
huntingtin (via lentiviral gene delivery) faithfully reproduce the
gene expression changes seen in human HD. Neither viral infection
nor unrelated (enhanced green fluorescent protein) transgene expression
had a major effect on resultant RNA profiles. Expression of a wild-type
fragment of huntingtin [htt171-18Q] also caused only a small number
of RNA changes. The disease-related signal in htt171-82Q versus htt171-18Q
comparisons was far greater, resulting in the differential detection
of 20% of all mRNA probe sets. Transcriptomic effects of mutated
htt171 are time- and polyglutamine-length dependent and occur in
parallel with other manifestations of polyglutamine toxicity over
4-8 weeks. Specific RNA changes in htt171-82Q-expressing striatal
cells accurately recapitulated those observed in human HD caudate
and included decreases in PENK (proenkephalin), RGS4 (regulator of
G-protein signaling 4), dopamine D1 receptor (DRD1), DRD2, CNR1 (cannabinoid
CB1 receptor), and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32;
also known as PPP1R1B) mRNAs. HD-related transcriptomic changes were
also observed in primary neurons expressing a longer fragment of
mutant huntingtin (htt853-82Q). The gene expression changes observed
in cultured striatal neurons are not secondary to abnormalities of
neuronal firing or glutamatergic, dopaminergic, or brain-derived
neurotrophic factor signaling, thereby demonstrating that HD-induced
dysregulation of the striatal transcriptome might be attributed to
intrinsic effects of mutant huntingtin.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/39/9723}
}
@ARTICLE{Rupp2006,
author = {Rupp, C and Dolznig, H and Puri, C and Schweifer, N and Sommergruber,
W and Kraut, N and Rettig, WJ and Kerjaschki, D and Garin-Chesa,
P},
title = {Laser capture microdissection of epithelial cancers guided by antibodies
against fibroblast activation protein and endosialin.},
journal = {Diagn Mol Pathol},
year = {2006},
volume = {15},
pages = {35-42--},
number = {1},
month = mar,
abstract = {Transcriptional profiling of cancer biopsies is used extensively to
identify expression signatures for specific cancer types, diagnostic
and prognostic subgroups, and novel molecular targets for therapy.
To broaden these applications, several challenges remain. For example,
the integrity of RNA extracted even from small tissue samples has
to be insured and monitored. Moreover, total tumor RNA may hide the
marked histologic heterogeneity of human cancers. A principle approach
to this heterogeneity has been provided by laser capture microdissection
performed on antibody-stained tissue sections (immuno-LCM; iLCM).
In this study, we have established a procedure to assess the quality
of RNA obtained from tissue sections, coupled with immunostaining
using antibodies to different tumor stromal markers, and subsequent
iLCM to selectively capture the cancer stroma compartments. The procedure
was applied to 53 frozen specimens of human epithelial cancers. Sections
were stained for histopathological evaluation, and RNA was isolated
from adjacent serial sections. RNA quality was assessed by the Agilent-Bioanalyzer
(Agilent, Palo Alto, CA) and by multiplex RT-PCR. Two thirds of the
specimens were found to yield good to excellent RNA quality. For
microdissection of the tumor stroma with reactive fibroblasts and
tumor blood vessels, a rapid incubation protocol with antibodies
against fibroblast activation protein (FAP) and against endosialin
was developed to ensure RNA integrity for subsequent iLCM. Using
these procedures, RNA from distinct tumor compartments can be isolated,
analyzed, amplified, and used for transcription profiling.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16531767}
}
@ARTICLE{Rush2009,
author = {Rush, Catherine and Nyara, Moses and Moxon, Joseph and Trollope,
Alexandra and Cullen, Bradford and Golledge, Jonathan},
title = {Whole genome expression analysis within the angiotensin II-apolipoprotein
E deficient mouse model of abdominal aortic aneurysm},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {298},
number = {1},
abstract = {BACKGROUND:An animal model commonly used to investigate pathways and
potential therapeutic interventions relevant to abdominal aortic
aneurysm (AAA) involves subcutaneous infusion of angiotensin II within
the apolipoprotein E deficient mouse. The aim of this study was to
investigate genes differentially expressed in aneurysms forming within
this mouse model in order to assess the relevance of this model to
human AAA.RESULTS:Using microarrays we identified genes relevant
to aneurysm formation within apolipoprotein E deficient mice. Firstly
we investigated genes differentially expressed in the aneurysm prone
segment of the suprarenal aorta in these mice. Secondly we investigated
genes that were differentially expressed in the aortas of mice developing
aneurysms relative to those that did not develop aneurysms in response
to angiotensin II infusion. Our findings suggest that a host of inflammation
and extracellular matrix remodelling pathways are upregulated within
the aorta in mice developing aneurysms. Kyoto Encyclopedia of Genes
and Genome categories enriched in the aortas of mice with aneurysms
included cytokine-cytokine receptor interaction, leukocyte transendothelial
migration, natural killer cell mediated cytotoxicity and hematopoietic
cell lineage. Genes associated with extracellular matrix remodelling,
such as a range of matrix metalloproteinases were also differentially
expressed in relation to aneurysm formation.CONCLUSION:This study
is the first report describing whole genome expression arrays in
the apolipoprotein E deficient mice in relation to aneurysm formation.
The findings suggest that the pathways believed to be critical in
human AAA are also relevant to aneurysm formation in this mouse model.
The findings therefore support the value of this model to investigate
interventions and mechanisms of human AAA.},
doi = {10.1186/1471-2164-10-298},
issn = {1471-2164},
pubmedid = {19580648},
url = {http://www.biomedcentral.com/1471-2164/10/298}
}
@ARTICLE{Russell2011,
author = {Russell, Joanne and Bayer, Micha and Booth, Clare and Cardle, Linda
and Hackett, Christine and Hedley, Pete and Jorgensen, Linzi and
Morris, Jenny and Brennan, Rex},
title = {Identification, utilisation and mapping of novel transcriptome-based
markers from blackcurrant (Ribes nigrum)},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {147},
number = {1},
abstract = {BACKGROUND:Deep-level second generation sequencing (2GS) technologies
are now being applied to non-model species as a viable and favourable
alternative to Sanger sequencing. Large-scale SNP discovery was undertaken
in blackcurrant (Ribes nigrum L.) using transcriptome-based 2GS 454
sequencing on the parental genotypes of a reference mapping population,
to generate large numbers of novel markers for the construction of
a high-density linkage map.RESULTS:Over 700,000 reads were produced,
from which a total of 7,000 SNPs were found. A subset of polymorphic
SNPs was selected to develop a 384-SNP OPA assay using the Illumina
BeadXpress platform. Additionally, the data enabled identification
of 3,000 novel EST-SSRs. The selected SNPs and SSRs were validated
across diverse Ribes germplasm, including mapping populations and
other selected Ribes species.SNP-based maps were developed from two
blackcurrant mapping populations, incorporating 48% and 27% of assayed
SNPs respectively. A relatively high proportion of visually monomorphic
SNPs were investigated further by quantitative trait mapping of theta
score outputs from BeadStudio analysis, and this enabled additional
SNPs to be placed on the two maps.CONCLUSIONS:The use of 2GS technology
for the development of markers is superior to previously described
methods, in both numbers of markers and biological informativeness
of those markers. Whilst the numbers of reads and assembled contigs
were comparable to similar sized studies of other non-model species,
here a high proportion of novel genes were discovered across a wide
range of putative function and localisation. The potential utility
of markers developed using the 2GS approach in downstream breeding
applications is discussed.},
doi = {10.1186/1471-2229-11-147},
issn = {1471-2229},
pubmedid = {22035129},
url = {http://www.biomedcentral.com/1471-2229/11/147}
}
@ARTICLE{Russell2008,
author = {Russell, Scott D. and Bhalla, Prem L. and Singh, Mohan B.},
title = {Transcriptome-Based Examination of Putative Pollen Allergens of Rice
(Oryza sativa ssp. japonica)},
journal = {Mol Plant},
year = {2008},
volume = {1},
pages = {751--759},
number = {5},
month = sep,
abstract = {Pollen allergens are among the most abundantly transcribed and translated
products in the life history of plants, and particularly grasses.
To identify different pollen allergens in rice, putative allergens
were identified in the rice genome and their expression characterized
using the Affymetrix 57K rice GeneChip microarray. Among the most
abundant pollen-specific candidate transcripts were Ory s 1 beta-expansin,
Ory s 2, Ory s 7 EF hand, Ory s 11, Ory s 12 profilin A, Ory s 23,
glycosyl hydrolase family 28 (polygalacturonase), and FAD binding
proteins. Highly expressed pollen proteins are frequently present
in multiple copy numbers, sometimes with mirror images located on
nearby regions of the opposite DNA strand. Many of these are intronless
and inserted as copies that retain nearly exact copies of their regulatory
elements. Ory s 23 reflects low variability and high copy number,
suggesting recent gene amplification. Some copies contain pseudogenes,
which may reflect their origin through activity of retrotransposition;
some putative allergenic sequences bear fusion products with repeat
sequences of transposable elements (LTRs). The abundance of nearby
repetitive sequences, activation of transposable elements, and high
production of mRNA transcripts appear to coincide in pollen and may
contribute to a syndrome in which highly transcribed proteins may
be copied and inserted with streamlined features for translation,
including grouping and removal of introns.},
url = {http://mplant.oxfordjournals.org/cgi/content/abstract/1/5/751}
}
@ARTICLE{Russo2011,
author = {Russo, L. M. and Sadeghi, N. and Bate, K. and Comper, W. D. and Skog,
J. and Petrylak, D. P. and McKiernan, J. M.},
title = {Use of urinary microvesicles for noninvasive mRNA expression analysis
in patients with prostate cancer.},
journal = {ASCO Meeting Abstracts},
year = {2011},
volume = {29},
pages = {e15033},
number = {15_suppl},
abstract = {e15033 Background: Microvesicles (including exosomes) are small lipid
bilayer vesicles released from all cells into bodily fluids and have
been shown to harbor both RNA and DNA from the parent cell from which
they were released. Recently, a rapid method to extract high integrity
RNA from microvesicles was developed allowing reliable assessment
of their mRNA content. This allows us to gain a transcriptional profile
of organs such as the prostate without the need for invasive biopsy.
Here we use microvesicles to examine the expression pattern of various
genes associated with prostate cancer including the fusion marker
TMPRSS:ERG previously shown to be expressed in ~50% of all prostate
cancer patients. Methods: A voided (without DRE) or catheterized
urine sample was collected from patients with known or suspected
prostate cancer from Columbia University Medical Center under approved
IRB guidelines. Microvesicles were isolated using a rapid in-house
filtration based isolation technique. During RNA extraction a DNase
step was included to remove contaminating DNA. RNA integrity was
assessed using the Agilent Bioanalyzer. Isolated RNA was used to
assess the expression of key prostate markers such as PSA, PCA3 and
TMPRSS:ERG. Results: RNA with visible rRNA peaks was successfully
isolated from all urine samples assessed. Prostate marker transcripts
for PSA, PCA3 and TMPRSS:ERG could be readily detected without the
need for a DRE. An initial blinded pilot study of 11 patients revealed
that 4 patients were shown to express TMPRSS:ERG mRNA and that these
patients corresponded to known prostate cancer patients. TMPRSS:ERG
was undetectable in controls and patients with benign prostatic hyperplasia
or previously removed prostate cancers. Conclusions: The gene expression
profile of prostate cancer patients and controls can be elucidated
by isolation of microvesicle mRNA in a voided sample without the
need for a DRE. This novel diagnostic tool is currently being investigated
in a cohort of 100 cancer patients and controls.},
url = {http://meeting.ascopubs.org/cgi/content/abstract/29/15_suppl/e15033}
}
@ARTICLE{Russom2008,
author = {Russom, Aman and Sethu, Palaniappan and Irimia, Daniel and Mindrinos,
Michael N. and Calvano, Steve E. and Garcia, Iris and Finnerty, Celeste
and Tannahill, Cynthia and Abouhamze, Amer and Wilhelmy, Julie and
Lopez, M. Cecilia and Baker, Henry V. and Herndon, David N. and Lowry,
Stephen F. and Maier, Ronald V. and Davis, Ronald W. and Moldawer,
Lyle L. and Tompkins, Ronald G. and Toner, Mehmet and the Inflammation
and Host Response to Injury Large Scale Collaborative Research Program},
title = {Microfluidic Leukocyte Isolation for Gene Expression Analysis in
Critically Ill Hospitalized Patients},
journal = {Clin. Chem.},
year = {2008},
volume = {54},
pages = {891--900},
number = {5},
month = may,
abstract = {Background: Microarray technology is becoming a powerful tool for
diagnostic, therapeutic, and prognostic applications. There is at
present no consensus regarding the optimal technique to isolate nucleic
acids from blood leukocyte populations for subsequent expression
analyses. Current collection and processing techniques pose significant
challenges in the clinical setting. Here, we report the clinical
validation of a novel microfluidic leukocyte nucleic acid isolation
technique for gene expression analysis from critically ill, hospitalized
patients that can be readily used on small volumes of blood. Methods:
We processed whole blood from hospitalized patients after burn injury
and severe blunt trauma according to the microfluidic and standard
macroscale leukocyte isolation protocol. Side-by-side comparison
of RNA quantity, quality, and genome-wide expression patterns was
used to clinically validate the microfluidic technique. Results:
When the microfluidic protocol was used for processing, sufficient
amounts of total RNA were obtained for genome-wide expression analysis
from 0.5 mL whole blood. We found that the leukocyte expression patterns
from samples processed using the 2 protocols were concordant, and
there was less variability introduced as a result of harvesting method
than there existed between individuals. Conclusions: The novel microfluidic
approach achieves leukocyte isolation in <25 min, and the quality
of nucleic acids and genome expression analysis is equivalent to
or surpasses that obtained from macroscale approaches. Microfluidics
can significantly improve the isolation of blood leukocytes for genomic
analyses in the clinical setting.},
url = {http://www.clinchem.org/cgi/content/abstract/54/5/891}
}
@ARTICLE{Rutar2011a,
author = {Rutar, Matt and Natoli, Riccardo and Kozulin, Peter and Valter, Krisztina
and Gatenby, Paul and Provis, Jan M.},
title = {Analysis of Complement Expression in Light-Induced Retinal Degeneration:
Synthesis and Deposition of C3 by Microglia/Macrophages Is Associated
with Focal Photoreceptor Degeneration},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {5347-5358},
number = {8},
abstract = {Purpose.To investigate the expression and localization of complement
system mRNA and protein in a light-induced model of progressive retinal
degeneration. Methods.Sprague-Dawley (SD) rats were exposed to 1000
lux of bright continuous light (BCL) for up to 24 hours. At time
points during (1-24 hours) and after (3 and 7 days) exposure, the
animals were euthanatized and the retinas processed. Differential
expression of complement genes at 24 hours of exposure was assessed
using microarray analysis. Expression of complement genes was validated
by quantitative PCR, and expression of selected genes was investigated
during and after BCL exposure. Photoreceptor apoptosis was assessed
using TUNEL and C3 was further investigated by spatiotemporal analysis
using in situ hybridization and immunohistochemistry. Results.Exposure
to 24 hours of BCL induced differential expression of a suite of
complement system genes, including classic and lectin components,
regulators, and receptors. C1qr1, MCP, Daf1, and C1qTNF6 all modulated
in concert with photoreceptor death and AP-1 expression, which reached
a peak at 24 hours exposure. C1s and C4a reached peak expression
at 3 days after exposure, while expression of C3, C3ar1, and C5r1
were maximum at 7 days after exposure. C3 mRNA was detected in ED1-
and IBA1-positive microglia/macrophages, in the retinal vessels and
optic nerve head and in the subretinal space, particularly at the
margins of the emerging lesion. Conclusions.The data indicate that
BCL induces the prolonged expression of a range of complement genes
and show that microglia/macrophages synthesize C3 and deposit it
in the ONL after BCL injury. These findings have relevance to the
role of complement in progressive retinal degeneration, including
atrophic AMD.},
doi = {10.1167/iovs.10-7119},
eprint = {http://www.iovs.org/cgi/reprint/52/8/5347.pdf},
url = {http://www.iovs.org/cgi/content/abstract/52/8/5347}
}
@ARTICLE{Rutar2011,
author = {Rutar, Matt and Natoli, Riccardo and Valter, Krisztina and Provis,
Jan M.},
title = {Early Focal Expression of the Chemokine Ccl2 by Muller Cells during
Exposure to Damage-Inducing Bright Continuous Light},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {2379--2388},
number = {5},
month = apr,
abstract = {Purpose.To investigate the time course and localization of Ccl2 expression
and recruitment of inflammatory cells associated with light-induced
photoreceptor degeneration. Methods.Sprague-Dawley (SD) rats were
exposed to 1000 lux light for up to 24 hours, after which some animals
were allowed to recover in dim light (5 lux) for 3 or 7 days. During
and after exposure to light, the animals were euthanatized and the
retinas processed. Ccl2 expression was assessed by qPCR, immunohistochemistry,
and in situ hybridization at each time point. Counts were made of
perivascular monocytes/microglia immunolabeled with ED1, and photoreceptor
apoptosis was assessed with TUNEL. Results.Upregulation of Ccl2 expression
was evident in the retina by 12 hours of exposure and correlated
with increased photoreceptor death. Ccl2 expression reached its maximum
at 24 hours, coinciding with peak cell death. Immunohistochemistry
and in situ hybridization showed that Ccl2 is expressed by Muller
cells from 12 hours of exposure, most intensely in the superior retina,
in the region of the incipient light-induced lesion. After the Muller
cell-driven expression of Ccl2, there was a substantial recruitment
of monocytes to the local retina and choroidal vasculature. This
coincided spatially with the expression of Ccl2 in the superior retina.
Peak monocyte infiltration followed maximum Ccl2 expression by up
to 3 days. Furthermore, Ccl2 immunoreactivity was observed in many
infiltrating monocytes after a 24-hour exposure. Conclusions.The
data indicate that photoreceptor death promotes region-specific expression
of Ccl2 by Muller cells, which facilitates targeting of monocytes
to sites of injury. The data suggest that recruitment of monocytes
to developing lesions is secondary to signaling events in the retina.},
comment = {10.1167/iovs.10-6010},
url = {http://www.iovs.org/cgi/content/abstract/52/5/2379}
}
@ARTICLE{Rutella2006,
author = {Rutella, Sergio and Bonanno, Giuseppina and Procoli, Annabella and
Mariotti, Andrea and de Ritis, Daniela G. and Curti, Antonio and
Danese, Silvio and Pessina, Gloria and Pandolfi, Simona and Natoni,
Federica and Di Febo, Annalaura and Scambia, Giovanni and Manfredini,
Rossella and Salati, Simona and Ferrari, Sergio and Pierelli, Luca
and Leone, Giuseppe and Lemoli, Roberto M.},
title = {Hepatocyte growth factor favors monocyte differentiation into regulatory
interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell
features},
journal = {Blood},
year = {2006},
volume = {108},
pages = {218--227},
number = {1},
month = jul,
abstract = {Several hematopoietic growth factors, including interleukin-10 (IL-10)
and transforming growth factor-[beta]1 (TGF-[beta]1), promote the
differentiation of tolerogenic dendritic cells (DCs). Hepatocyte
growth factor (HGF) is a pleiotropic cytokine whose effects on human
DC differentiation and function have not been investigated. Monocytes
cultured with HGF (HGFMo) differentiated into accessory cells with
DC-like morphology, released low amounts of IL-12p70 and up-regulated
IL-10 both at the mRNA and at the protein level. Upon activation
with HGFMo, allogeneic CD4+CD25- T cells expressed the T regulatory
(Treg)-associated transcription factor FoxP3, proliferated poorly,
and released high levels of IL-10. Interestingly, blockade of surface
immunoglobulin-like transcript 3 (ILT3) on HGFMo or neutralization
of secreted IL-10 translated into partial restoration of T-cell proliferation.
Secondary stimulation of HGFMo-primed CD4+ T cells with immunogenic
DCs differentiated with granulocyte-macrophage colony-stimulating
factor (GM-CSF) and IL-4 from monocytes of the same donor resulted
in measurable T-cell proliferation. HGFMo-primed CD4+ T cells significantly
inhibited the proliferation of naive CD4+CD25- T cells in a cell-contact-dependent
manner. Finally, DNA microarray analysis revealed a unique gene-expression
profile of HGF-activated monocytes. Collectively, our findings point
to a novel role for HGF in the regulation of monocyte/DC functions
that might be exploited therapeutically. (Blood. 2006;108:218-227)},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/108/1/218}
}
@ARTICLE{Rutherford2010,
author = {Rutherford, Becky J. and Dahl, Robert H. and Price, Richard E. and
Szmidt, Heather L. and Benke, Peter I. and Mukhopadhyay, Aindrila
and Keasling, Jay D.},
title = {Functional Genomic Study of Exogenous n-Butanol Stress in Escherichia
coli},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {1935--1945},
number = {6},
month = mar,
abstract = {n-Butanol has been proposed as an alternative biofuel to ethanol,
and several industrially used microbes, including Escherichia coli,
have been engineered to produce it. Unfortunately, n-butanol is more
toxic than ethanol to these organisms. To understand the basis for
its toxicity, cell-wide studies were conducted at the transcript,
protein, and metabolite levels to obtain a global view of the n-butanol
stress response. Analysis of the data indicates that n-butanol stress
has components common to other stress responses, including perturbation
of respiratory functions (nuo and cyo operons), oxidative stress
(sodA, sodC, and yqhD), heat shock and cell envelope stress (rpoE,
clpB, htpG, cpxR, and cpxP), and metabolite transport and biosynthesis
(malE and opp operon). Assays using fluorescent dyes indicated a
large increase in reactive oxygen species during n-butanol stress,
confirming observations from the microarray and proteomics measurements.
Mutant strains with mutations in several genes whose products changed
most dramatically during n-butanol stress were examined for increased
sensitivity to n-butanol. Results from these analyses allowed identification
of key genes that were recruited to alleviate oxidative stress, protein
misfolding, and other causes of growth defects. Cellular engineering
based on these cues may assist in developing a high-titer, n-butanol-producing
host.},
url = {http://aem.asm.org/cgi/content/abstract/76/6/1935}
}
@ARTICLE{Rutherford2006,
author = {Rutherford, R.B. and Foster, B.L. and Bammler, T. and Beyer, R.P.
and Sato, S. and Somerman, M.J.},
title = {Extracellular Phosphate Alters Cementoblast Gene Expression},
journal = {Journal of Dental Research},
year = {2006},
volume = {85},
pages = {505--509},
number = {6},
month = jun,
abstract = {Genetic data from humans and mice reveal that the formation of cementum
is sensitive to intra- and extracellular phosphate/pyrophosphate
distribution. The intracellular molecular pathways whereby altered
levels of extracellular phosphate concentration may affect cementum
formation have not been elucidated. To initiate inquiry, we have
studied the temporal effects of extracellular phosphate on global
patterns of gene expression in a line of immortalized mouse cementoblasts.
Total RNA from cultured cementoblasts treated with 5 mM inorganic
phosphate over a designated time period, from 1-48 hrs, was analyzed
for global patterns of gene expression by means of DNA microarrays
representing the complete mouse genome. Analyses of significant hybridization
signals indicated that 5 mM extracellular phosphate alters the expression
of genes comprising several gene ontology (GO) groups, including
transcription factor activity and Wnt signaling.},
url = {http://jdr.sagepub.com/cgi/content/abstract/85/6/505}
}
@ARTICLE{Ruttink2007,
author = {Ruttink, Tom and Arend, Matthias and Morreel, Kris and Storme, Veronique
and Rombauts, Stephane and Fromm, Jorg and Bhalerao, Rishikesh P.
and Boerjan, Wout and Rohde, Antje},
title = {A Molecular Timetable for Apical Bud Formation and Dormancy Induction
in Poplar},
journal = {PLANT CELL},
year = {2007},
volume = {19},
pages = {2370--2390},
number = {8},
month = aug,
abstract = {The growth of perennial plants in the temperate zone alternates with
periods of dormancy that are typically initiated during bud development
in autumn. In a systems biology approach to unravel the underlying
molecular program of apical bud development in poplar (Populus tremula
x Populus alba), combined transcript and metabolite profiling were
applied to a high-resolution time course from short-day induction
to complete dormancy. Metabolite and gene expression dynamics were
used to reconstruct the temporal sequence of events during bud development.
Importantly, bud development could be dissected into bud formation,
acclimation to dehydration and cold, and dormancy. To each of these
processes, specific sets of regulatory and marker genes and metabolites
are associated and provide a reference frame for future functional
studies. Light, ethylene, and abscisic acid signal transduction pathways
consecutively control bud development by setting, modifying, or terminating
these processes. Ethylene signal transduction is positioned temporally
between light and abscisic acid signals and is putatively activated
by transiently low hexose pools. The timing and place of cell proliferation
arrest (related to dormancy) and of the accumulation of storage compounds
(related to acclimation processes) were established within the bud
by electron microscopy. Finally, the identification of a large set
of genes commonly expressed during the growth-to-dormancy transitions
in poplar apical buds, cambium, or Arabidopsis thaliana seeds suggests
parallels in the underlying molecular mechanisms in different plant
organs.},
url = {http://www.plantcell.org/cgi/content/abstract/19/8/2370}
}
@ARTICLE{Ruzicka2010,
author = {Ruzicka, Daniel and Barrios-Masias, Felipe and Hausmann, Natasha
and Jackson, Louise and Schachtman, Daniel},
title = {Tomato root transcriptome response to a nitrogen-enriched soil patch},
journal = {BMC Plant Biology},
year = {2010},
volume = {10},
pages = {75},
number = {1},
abstract = {BACKGROUND:Nitrogen (N), the primary limiting factor for plant growth
and yield in agriculture, has a patchy distribution in soils due
to fertilizer application or decomposing organic matter. Studies
in solution culture over-simplify the complex soil environment where
microbial competition and spatial and temporal heterogeneity challenge
roots' ability to acquire adequate amounts of nutrients required
for plant growth. In this study, various ammonium treatments (as
15N) were applied to a discrete volume of soil containing tomato
(Solanum lycopersicum) roots to simulate encounters with a localized
enriched patch of soil. Transcriptome analysis was used to identify
genes differentially expressed in roots 53 hrs after treatment.RESULTS:The
ammonium treatments resulted in significantly higher concentrations
of both ammonium and nitrate in the patch soil. The plant roots and
shoots exhibited increased levels of 15N over time, indicating a
sustained response to the enriched environment. Root transcriptome
analysis identified 585 genes differentially regulated 53 hrs after
the treatments. Nitrogen metabolism and cell growth genes were induced
by the high ammonium (65 µg NH4+-N g-1 soil), while stress response
genes were repressed. The complex regulation of specific transporters
following the ammonium pulse reflects a simultaneous and synergistic
response to rapidly changing concentrations of both forms of inorganic
N in the soil patch. Transcriptional analysis of the phosphate transporters
demonstrates cross-talk between N and phosphate uptake pathways and
suggests that roots increase phosphate uptake via the arbuscular
mycorrhizal symbiosis in response to N.CONCLUSION:This work enhances
our understanding of root function by providing a snapshot of the
response of the tomato root transcriptome to a pulse of ammonium
in a complex soil environment. This response includes an important
role for the mycorrhizal symbiosis in the utilization of an N patch.},
doi = {10.1186/1471-2229-10-75},
issn = {1471-2229},
pubmedid = {20423508},
url = {http://www.biomedcentral.com/1471-2229/10/75}
}
@ARTICLE{Ruzinova2003,
author = {Ruzinova, Marianna B. and Schoer, Rebecca A. and Gerald, William
and Egan, James E. and Pandolfi, Pier Paolo and Rafii, Shahin and
Manova, Katia and Mittal, Vivek and Benezra, Robert},
title = {Effect of angiogenesis inhibition by Id loss and the contribution
of bone-marrow-derived endothelial cells in spontaneous murine tumors},
journal = {Cancer Cell},
year = {2003},
volume = {4},
pages = {277--289},
number = {4},
month = oct,
abstract = {Angiogenic defects in Id mutant mice inhibit the growth of tumor xenografts,
providing a genetic model for antiangiogenic stress. Our work tests
the consequences of such stress on progression of more physiological
Pten+/- tumors. While tumor growth occurs despite impaired angiogenesis,
disruption of vasculature by Id loss causes tumor cells to experience
hypoxia and necrosis, the extent of which is tumor dependent. We
show that bone-marrow-derived endothelial precursors contribute functionally
to neovasculature of some but not all Pten+/- tumors, partially rescuing
Id mutant phenotype. We demonstrate that loss of Id1 in tumor endothelial
cells results in downregulation of several proangiogenic genes, including
[alpha]6 and [beta]4 integrins, matrix metalloprotease-2, and fibroblast
growth factor receptor-1. Inhibition of these factors phenocopies
loss of Id in in vivo angiogenesis assays.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-4CYN2PH-5/2/1aedfe37f1e40628b2dacf0080a5f43c}
}
@ARTICLE{Ryan2004,
author = {Ryan, Cindy A. and Gildea, Lucy A. and Hulette, Ben C. and Dearman,
Rebecca J. and Kimber, Ian and Gerberick, G. Frank},
title = {Gene expression changes in peripheral blood-derived dendritic cells
following exposure to a contact allergen},
journal = {Toxicology Letters},
year = {2004},
volume = {150},
pages = {301--316},
number = {3},
month = may,
abstract = {A critical step in the induction of allergic contact allergy is the
activation and subsequent migration of Langerhans cells (LC), an
important antigen presenting dendritic cell (DC) of the skin. As
the Langerhans cells migrate, they undergo a maturation process.
It has been proposed that contact allergen exposure can induce DC
maturation. While changes in DC gene expression profiles induced
by various maturation stimuli have been explored, there are no published
reports describing genomic-scale analysis of the changes induced
by chemical allergen exposure. Therefore, to explore the concept
of chemical allergen-induced DC maturation and to identify genes
that are regulated by exposure to allergens we examined, at the transcriptional
level, the effects of exposure to a contact allergen on DC. Peripheral
blood-derived DC were exposed for 24 h to either 1 mM or 5 mM dinitrobenzenesulfonic
acid (DNBS). Changes in gene expression were analyzed using Affymetrix
U95Av2 GeneChip®. Comparison of mean signal values from replicate
cultures revealed 173 genes that were significantly different (P<=0.001)
between 1 mM DNBS treated and untreated control DC and 1249 significant
gene changes between 5 mM DNBS treated and control DC. Real-time
reverse-transcriptase polymerase chain reaction (RT-PCR) was used
to evaluate the observed transcript changes for selected genes in
DC derived from a second donor. Comparison of the fold-changes in
transcript levels between the two platforms and donors revealed a
good correlation in both direction and magnitude. RT-PCR analysis
was also used to assess the allergen specificity of a selected number
of genes in DC derived from a third donor. Many of the gene expression
changes were found to be induced only by exposure to the allergen,
DNBS, and not by exposure to a structurally similar non-allergen,
benzenesulfonic acid. A number of gene expression changes induced
by allergen exposure were found to be consistent with what is known
of the DC maturation process, and thus provide support for the theory
of contact allergen-induced DC maturation. Additionally, it is hoped
that some of the transcript changes identified through this approach
will be shown to be suitable for use in the development of an in
vitro predictive assay for contact sensitization.},
issn = {0378-4274},
keywords = {Contact allergy, Dendritic cells, Gene expression, In vitro method,
Dinitrobenzenesulfonic acid},
url = {http://www.sciencedirect.com/science/article/B6TCR-4BWYSB8-4/2/42f50c0a90bdab86dfe3735a6f783b6e}
}
@ARTICLE{Ryan2011a,
author = {Ryan, E. J. and Stevenson, N. J. and Hegarty, J. E. and O’Farrelly,
C.},
title = {Chronic hepatitis C infection blocks the ability of dendritic cells
to secrete IFN-α and stimulate T-cell proliferation},
journal = {Journal of Viral Hepatitis},
year = {2011},
volume = {18},
pages = {840--851},
number = {12},
abstract = {Summary.  Dendritic cells (DCs) are likely to play a key role in
the compromised T-cell function associated with hepatitis C Virus
(HCV) infection. However, studies of DC function in HCV-infected
patients to date have yielded conflicting findings possibly because
of patient and virus heterogeneity. Here, we report the characterization
of monocyte-derived DCs obtained from a homogenous cohort of women
who were infected with HCV genotype 1b following exposure to contaminated
anti-D immunoglobulin from a single donor source. Patients included
in the study had not received anti-viral therapy and all had mild
liver disease. We show that phenotypically normal monocyte-derived
dendritic cells (MDDCs) (CD11c+HLA−DR+CD1a+CD14lo) can be obtained
from these patients. These cells respond to both Poly(I:C) and LPS,
by up-regulating expression of CD86. They secrete high levels of
IL-8 and CCL5 in response to LPS, an indication that the MyD88-dependent
and MyD88-independent signalling pathways downstream of TLR4 ligation
are functioning normally. However, these cells are poor stimulators
of T-cell proliferation in allogeneic mixed lymphocyte reactions.
Furthermore, patient MDDCs fail to secrete IFN-α in response to
poly(I:C) or IFN-β stimulation. Altered DC function may contribute
to impaired cellular immune responses and chronicity of disease following
HCV infection in this cohort. An effective therapeutic vaccine for
chronic HCV infection will most likely need to target DCs to elicit
an appropriate cellular response; therefore, it is important to resolve
how the DCs of different patient cohorts respond to stimulation via
TLRs.},
doi = {10.1111/j.1365-2893.2010.01384.x},
issn = {1365-2893},
keywords = {cytokines, dendritic cell, hepatitis C virus, IFN-α, T-cell proliferation,
toll-like receptor},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2893.2010.01384.x}
}
@ARTICLE{Ryan2010,
author = {Ryan, James and Morey, Jeanine and Bottein, Marie-Yasmine and Ramsdell,
John and Van Dolah, Frances},
title = {Gene expression profiling in brain of mice exposed to the marine
neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective
response},
journal = {BMC Neuroscience},
year = {2010},
volume = {11},
pages = {107},
number = {1},
abstract = {BACKGROUND:Ciguatoxins (CTXs) are polyether marine neurotoxins and
potent activators of voltage-gated sodium channels. This toxin is
carried by multiple reef-fish species and human consumption of ciguatoxins
can result in an explosive gastrointestinal/neurologic illness. This
study characterizes the global transcriptional response in mouse
brain to a symptomatic dose of the highly toxic Pacific ciguatoxin
P-CTX-1 and additionally compares this data to transcriptional profiles
from liver and whole blood examined previously. Adult male C57/BL6
mice were injected with 0.26 ng/g P-CTX-1 while controls received
only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional
profiling was performed on brain RNA with Agilent whole genome microarrays.
RT-PCR was used to independently validate gene expression and the
web tool DAVID was used to analyze gene ontology (GO) and molecular
pathway enrichment of the gene expression data.RESULTS:A pronounced
4°C hypothermic response was recorded in these mice, reaching a minimum
at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression
data were filtered by intensity, fold change and p-value, with the
resulting data used for time course analysis, K-means clustering,
ontology classification and KEGG pathway enrichment. Top GO hits
for this gene set included acute phase response and mono-oxygenase
activity. Molecular pathway analysis showed enrichment for complement/coagulation
cascades and metabolism of xenobiotics. Many immediate early genes
such as Fos, Jun and Early Growth Response isoforms were down-regulated
although others associated with stress such as glucocorticoid responsive
genes were up-regulated. Real time PCR confirmation was performed
on 22 differentially expressed genes with a correlation of 0.9 (Spearman's
Rho, p < 0.0001) with microarray results.CONCLUSIONS:Many of the
genes differentially expressed in this study, in parallel with the
hypothermia, figure prominently in protection against neuroinflammation.
Pathologic activity of the complement/coagulation cascade has been
shown in patients suffering from a chronic form of ciguatera poisoning
and is of particular interest in this model. Anti-inflammatory processes
were at work not only in the brain but were also seen in whole blood
and liver of these animals, creating a systemic anti-inflammatory
environment to protect against the initial cellular damage caused
by the toxin.},
doi = {10.1186/1471-2202-11-107},
issn = {1471-2202},
pubmedid = {20796285},
url = {http://www.biomedcentral.com/1471-2202/11/107}
}
@ARTICLE{Ryan2005,
author = {Ryan, J.C. and Morey, J.S. and Ramsdell, J.S. and van Dolah, F.M.},
title = {Acute phase gene expression in mice exposed to the marine neurotoxin
domoic acid},
journal = {Neuroscience},
year = {2005},
volume = {136},
pages = {1121--1132},
number = {4},
abstract = {Domoic acid is a rigid analog of the neurotransmitter glutamate and
a potent agonist of kainate subtype glutamate receptors. Persistent
activation of these receptor subtypes results in rapid excitotoxicity,
calcium dependent cell death and neuronal lesions in areas of the
brain where kainate pathways are concentrated. To better understand
responses to domoic acid induced excitotoxicity, microarrays were
used to profile gene expression in mouse brain following domoic acid
exposure. Adult female mice were subjected intraperitoneally to domoic
acid at the lethal dose 50, killed and dissected at 30, 60 and 240
min post-injection. Total brain RNA from treated mice was compared
with time-matched controls on Agilent 22K feature microarrays. Real-time
PCR was performed on selected genes. For the 30, 60 and 240 min time
points, 3.96%, 3.94% and 4.36% of the genes interrogated were differentially
expressed (P-value<=0.01), respectively. Rigorous filtering of the
data resulted in a set of 56 genes used for trending analysis and
K-medians and agglomerative clustering. The earliest genes induced
consisted primarily of early response gene families (Jun, Fos, Ier,
Egr, growth arrest and DNA damage 45) and the inflammatory response
element cyclooxygenase 2. Some later responding genes involved glucocorticoid
responses (Gilz, Sgk), cold inducible proteins (Cirbp, Rbm3), Map
kinases (Map3k6) and NF-[kappa]B inhibition. Real-time PCR in male
mice from an additional study confirmed the expression of several
of these genes across gender. The transcriptional profile induced
by domoic acid shared similarity with expression profiles of brain
ischemia and other excitotoxins, suggesting a common transcriptional
response.},
issn = {0306-4522},
keywords = {domoic acid, excitotoxicity, microarray, gene expression, ischemia,
marine biotoxin},
url = {http://www.sciencedirect.com/science/article/B6T0F-4H98T9K-6/2/79d150ca1a4c10cfbbbd4f2e73f965e7}
}
@ARTICLE{Ryan2007,
author = {Ryan, James C. and Bottein Dechraoui, Marie-Yasmine and Morey, Jeanine
S. and Rezvani, Amir and Levin, Edward D. and Gordon, Christopher
J. and Ramsdell, John S. and Van Dolah, Frances M.},
title = {Transcriptional profiling of whole blood and serum protein analysis
of mice exposed to the neurotoxin Pacific Ciguatoxin-1},
journal = {NeuroToxicology},
year = {2007},
volume = {28},
pages = {1099--1109},
number = {6},
month = nov,
abstract = {Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced
by the marine dinoflagellate Gambierdiscus sp., are potent activators
of voltage-gated sodium channels and a leading cause of human poisoning
from food fish. This report characterizes the genomic and proteomic
response in whole blood of adult male mice exposed i.p. to 264 ng/kg
of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24 h. Whole
genome microarray expression data were filtered by tightness of fit
between replicates, fold change (1.8) and p-value (10-5), resulting
in 183 annotated genes used for trending analysis, K-means clustering
and ontology classification. Genes involved with cytokine signaling,
proteasome complex and ribosomal function were dominant. qPCR performed
on 19 genes of interest had a correlation of 0.95 to array results
by Pearson's correlation coefficient. Serum protein analysis showed
small but significant changes in 6 of 60 proteins assayed: Ccl2,
Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression
was consistent with a Th2 immune response with interesting similarities
to expression seen in asthmatic models.},
issn = {0161-813X},
keywords = {Ciguatoxin, Microarray, Gene expression, Blood, Ciguatera, Biotoxin},
url = {http://www.sciencedirect.com/science/article/B6W81-4P06C7T-1/2/f950c2c27a889c096847d8654fbf0baf}
}
@ARTICLE{Ryan2005a,
author = {Ryan, Kieran A. and Karim, Najma and Worku, Mulugeta and Moore, Stanley
A. and Penn, Charles W. and O'Toole, Paul W.},
title = {HP0958 is an essential motility gene in Helicobacter pylori},
journal = {FEMS Microbiology Letters},
year = {2005},
volume = {248},
pages = {47--55},
number = {1},
month = jul,
abstract = {Motility is an essential colonization factor for the human gastric
pathogen Helicobacter pylori. The H. pylori genome encodes most known
flagellar proteins, although a number of key transcription regulators,
chaperones, and structural proteins have not yet been identified.
Using recently published yeast two-hybrid data we identified HP0958
as a potential motility-associated protein due to its strong interactions
with RpoN ([sigma]54) and FliH, a flagellar ATPase regulator. HP0958
exhibits no sequence similarity to any published flagellar genes
but contains a carboxy-terminal zinc finger domain that could function
in nucleic acid or protein binding. We created a HP0958 mutant by
inserting a chloramphenicol resistance marker into the gene using
a PCR-based allelic exchange method and the resultant mutant was
non-motile as measured by a BacTracker instrument. Electron microscopic
analysis revealed that the HP0958 mutant cells were aflagellate and
Western blot analysis revealed a dramatic reduction in flagellin
and hook protein production. The HP0958 mutant also showed decreased
transcription of flgE, flaB and flaA as well as the checkpoint genes
flhA and flhF. Expression of flgM was increased relative to the wild-type
and both rpoN and fliA ([sigma]28) expression were unchanged. We
conclude that HP0958 is essential for normal motility and flagella
production, and represents a novel flagellar component in the epsilon
proteobacteria.},
issn = {0378-1097},
keywords = {Helicobacter pylori, Flagella, Motility, Transcription},
url = {http://www.sciencedirect.com/science/article/B6T2W-4G94G83-7/2/f24d23dccb6a699edb72d7a764a87726}
}
@ARTICLE{Ryan2004a,
author = {Ryan, Margaret M. and Huffaker, Stephen J. and Webster, Maree J.
and Wayland, Matt and Freeman, Tom and Bahn, Sabine},
title = {Application and optimization of microarray technologies for human
postmortem brain studies},
journal = {Biological Psychiatry},
year = {2004},
volume = {55},
pages = {329--336},
number = {4},
month = feb,
abstract = {A number of microarray investigations using human postmortem brain
tissue have been published recently, exploring a multitude of human
brain disorders with the aim of unraveling the underlying pathologies.
Although the technology is still developing and lacks sufficient
sensitivity with regard to detecting splice variants and low abundance
transcripts, microarrays are becoming the prominent method for candidate
gene screening in complex neuropsychiatric disorders. The use of
postmortem tissue harbors a variety of potential pitfalls, however,
which could result in unreliable or, at worst, meaningless results.
During the course of our large-scale gene expression study on 150
human postmortem brain samples, using more than 200 Affymetrix GeneChips,
we have identified several aspects within microarray experimental
procedure that allows for the early identification of potentially
unreliable samples. The general application of the guidelines and
technical tips described here increase the efficiency, reliability,
and amount of data generated by this powerful screening technology
while reducing superfluous consumption of time and resources.},
issn = {0006-3223},
keywords = {Microarray, Affymetrix, postmortem, human brain, quality control},
url = {http://www.sciencedirect.com/science/article/B6T4S-4BG8VW2-H/2/960b7da0b1461647faa5a8036d672849}
}
@ARTICLE{Ryan2011,
author = {Ryan, Margaret M. and Mason-Parker, Sara E. and Tate, Warren P. and
Abraham, Wickliffe C. and Williams, Joanna M.},
title = {Rapidly induced gene networks following induction of long-term potentiation
at perforant path synapses in vivo},
journal = {Hippocampus},
year = {2011},
volume = {21},
pages = {541--553},
number = {5},
abstract = {Abstract The canonical view of the maintenance of long-term potentiation
(LTP), a widely accepted experimental model for memory processes,
is that new gene transcription contributes to its consolidation;
however, the gene networks involved are unknown. To address this
issue, we have used high-density Rat 230.2 Affymetrix arrays to establish
a set of genes induced 20-min post-LTP, and using Ingenuity Pathway
network analysis tools we have investigated how these early responding
genes are interrelated. This analysis identified LTP-induced regulatory
networks in which the transcription factors (TFs) nuclear factor-KB
and serum response factor, which, to date, have not been widely recognized
as coordinating the early gene response, play a key role alongside
the more well-known TFs cyclic AMP response element-binding protein,
and early growth response 1. Analysis of gene-regulatory promoter
sites and chromosomal locations of the genes within the dataset reinforced
the importance of these molecules in the early gene response and
predicted that the coordinated action might arise from gene clustering
on particular chromosomes. We have also identified a transcription-based
response that affects mitogen-activated protein kinase signaling
pathways and protein synthesis during the stabilization of the LTP
response. Furthermore, evidence from biological function, networks,
and regulatory analyses showed convergence on genes related to development,
proliferation, and neurogenesis, suggesting that these functions
are regulated early following LTP induction. This raises the interesting
possibility that LTP-related gene expression plays a role in both
synaptic reorganization and neurogenesis. © 2010 Wiley-Liss, Inc.},
doi = {10.1002/hipo.20770},
issn = {1098-1063},
keywords = {microarray, ingenuity pathway analysis, transcription factor, chromosome,
promoter},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hipo.20770}
}
@ARTICLE{Ryden2008,
author = {Ryden, Mikael and Agustsson, Thorhallur and Laurencikiene, Jurga
and Britton, Tom and Sjoelin, Eva and Isaksson, Bengt and Permert,
Johan and Arner, Peter},
title = {Lipolysis - Not inflammation, cell death, or lipogenesis - Is involved
in adipose tissue loss in cancer cachexia},
journal = {Cancer},
year = {2008},
volume = {113},
pages = {1695--1704},
number = {7},
abstract = {Abstract 10.1002/cncr.23802.abs BACKGROUND. Cancer cachexia is an
important, negative prognostic marker that has been linked to systemic
inflammation and cell death through unclear mechanisms. A key feature
of cancer cachexia is loss of white adipose tissue (WAT) because
of increased adipocyte lipolysis and possibly reduced lipid synthesis
(lipogenesis). In this study, the authors investigated whether alterations
in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration
could account for some of the functional changes observed in WAT
in cancer cachexia. METHODS. Blood and subcutaneous WAT samples were
obtained from a 10 weight-stable patients, from 13 weight losing
(cachexia) patients with cancer, and from 5 patients without cancer
(noncancer patients) who initially were classified with cancer. RESULTS.
Systemic inflammation (increased circulating levels of interleukin
6 [IL-6]) and enhanced lipolysis were confirmed in the cachectic
patients compared with the other patients. However, the messenger
RNA expression of IL-6 and other cytokine or leukocyte markers, as
well as WAT secretion of IL-6, were not altered in the patients with
cachexia. Thus, the elevated serum levels of IL-6 that were observed
in cachexia were not derived from WAT. Insulin-induced lipogenesis
in adipocytes from patients with cachexia was the same as that in
adipocytes from patients with weight-stable cancer and from noncancer
patients (2.5-fold maximal stimulation; half-maximum effective concentration,
∼0.03 nmol/L). Fat cell size was decreased but adipocyte numbers
were normal in cancer patients with cachexia, suggesting that there
was no major fat cell death. CONCLUSIONS. The current findings indicated
that subcutaneous WAT does not contribute to the systemic inflammatory
reaction and does not induce adipocyte insulin resistance in cancer
cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis
or adipocyte cell death, appeared to be the primary cause of fat
loss in this condition. Cancer 2008. © 2008 American Cancer Society.},
issn = {1097-0142},
keywords = {adipocyte, cytokine, interleukin 6, tumor necrosis factor α, inflammation,
lipogenesis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.23802}
}
@ARTICLE{Ryden2007,
author = {Ryden, Mikael and Jocken, Johan and van Harmelen, Vanessa and Dicker,
Andrea and Hoffstedt, Johan and Wiren, Mikael and Blomqvist, Lennart
and Mairal, Aline and Langin, Dominique and Blaak, Ellen and Arner,
Peter},
title = {Comparative studies of the role of hormone-sensitive lipase and adipose
triglyceride lipase in human fat cell lipolysis},
journal = {Am J Physiol Endocrinol Metab},
year = {2007},
volume = {292},
pages = {E1847--1855},
number = {6},
month = jun,
abstract = {Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)
regulate adipocyte lipolysis in rodents. The purpose of this study
was to compare the roles of these lipases for lipolysis in human
adipocytes. Subcutaneous adipose tissue was investigated. HSL and
ATGL protein expression were related to lipolysis in isolated mature
fat cells. ATGL or HSL were knocked down by RNA interference (RNAi)
or selectively inhibited, and effects on lipolysis were studied in
differentiated preadipocytes or adipocytes derived from human mesenchymal
stem cells (hMSC). Subjects were all women. There were 12 lean controls,
8 lean with polycystic ovary syndrome (PCOS), and 27 otherwise healthy
obese subjects. We found that norepinephrine-induced lipolysis was
positively correlated with HSL protein levels (P < 0.0001) but not
with ATGL protein. Women with PCOS or obesity had significantly decreased
norepinephrine-induced lipolysis and HSL protein expression but no
change in ATGL protein expression. HSL knock down by RNAi reduced
basal and catecholamine-induced lipolysis. Knock down of ATGL decreased
basal lipolysis but did not change catecholamine-stimulated lipolysis.
Treatment of hMSC with a selective HSL inhibitor during and/or after
differentiation in adipocytes reduced basal lipolysis by 50%, but
stimulated lipolysis was inhibited completely. In contrast to findings
in rodents, ATGL is of less importance than HSL in regulating catecholamine-induced
lipolysis and cannot replace HSL when this enzyme is continuously
inhibited. However, both lipases regulate basal lipolysis in human
adipocytes. ATGL expression, unlike HSL, is not influenced by obesity
or PCOS.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/292/6/E1847}
}
@ARTICLE{Ryge2010,
author = {Ryge, Jesper and Winther, Ole and Wienecke, Jacob and Sandelin, Albin
and Westerdahl, Ann-Charlotte and Hultborn, Hans and Kiehn, Ole},
title = {Transcriptional regulation of gene expression clusters in motor neurons
following spinal cord injury},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {365},
number = {1},
abstract = {BACKGROUND:Spinal cord injury leads to neurological dysfunctions affecting
the motor, sensory as well as the autonomic systems. Increased excitability
of motor neurons has been implicated in injury-induced spasticity,
where the reappearance of self-sustained plateau potentials in the
absence of modulatory inputs from the brain correlates with the development
of spasticity.RESULTS:Here we examine the dynamic transcriptional
response of motor neurons to spinal cord injury as it evolves over
time to unravel common gene expression patterns and their underlying
regulatory mechanisms. For this we use a rat-tail-model with complete
spinal cord transection causing injury-induced spasticity, where
gene expression profiles are obtained from labeled motor neurons
extracted with laser microdissection 0, 2, 7, 21 and 60 days post
injury. Consensus clustering identifies 12 gene clusters with distinct
time expression profiles. Analysis of these gene clusters identifies
early immunological/inflammatory and late developmental responses
as well as a regulation of genes relating to neuron excitability
that support the development of motor neuron hyper-excitability and
the reappearance of plateau potentials in the late phase of the injury
response. Transcription factor motif analysis identifies differentially
expressed transcription factors involved in the regulation of each
gene cluster, shaping the expression of the identified biological
processes and their associated genes underlying the changes in motor
neuron excitability.CONCLUSIONS:This analysis provides important
clues to the underlying mechanisms of transcriptional regulation
responsible for the increased excitability observed in motor neurons
in the late chronic phase of spinal cord injury suggesting alternative
targets for treatment of spinal cord injury. Several transcription
factors were identified as potential regulators of gene clusters
containing elements related to motor neuron hyper-excitability, the
manipulation of which potentially could be used to alter the transcriptional
response to prevent the motor neurons from entering a state of hyper-excitability.},
doi = {10.1186/1471-2164-11-365},
issn = {1471-2164},
pubmedid = {20534130},
url = {http://www.biomedcentral.com/1471-2164/11/365}
}
@ARTICLE{Ryjenkov2006,
author = {Ryjenkov, Dmitri A. and Simm, Roger and Romling, Ute and Gomelsky,
Mark},
title = {The PilZ Domain Is a Receptor for the Second Messenger c-di-GMP:
THE PilZ DOMAIN PROTEIN YcgR CONTROLS MOTILITY IN ENTEROBACTERIA},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {30310--30314},
number = {41},
month = oct,
abstract = {The ubiquitous bacterial second messenger c-di-GMP controls exopolysaccharide
synthesis, flagella- and pili-based motility, gene expression, and
interactions of bacteria with eukaryotic hosts. With the exception
of bacterial cellulose synthases, the identities of c-di-GMP receptors
and end targets have remained unknown. Recently, Amikam and Galperin
(Amikam, D., and Galperin, M. (2006) Bioinformatics 22, 3-6) hypothesized
that the PilZ domains present in the BcsA subunits of bacterial cellulose
synthases function in c-di-GMP binding. This hypothesis has been
tested here using the Escherichia coli PilZ domain protein YcgR,
its individual PilZ domain and the PilZ domain from Gluconacetobacter
xylinus BcsA. YcgR was purified and found to bind c-di-GMP tightly
and specifically, Kd 0.84 {micro}M. Individual PilZ domains from
YcgR and BcsA also bound c-di-GMP, albeit with lesser affinity, indicating
that PilZ is sufficient for binding. The site-directed mutagenesis
performed on YcgR implicated the most conserved residues in the PilZ
domain directly in c-di-GMP binding. It is suggested that c-di-GMP
binding to PilZ brings about conformational changes in the protein
that stabilize the bound ligand and initiate the downstream signal
transduction cascade. While the identity of the downstream partner(s)
of YcgR remains unknown, it is shown that YcgR regulates flagellum-based
motility in a c-di-GMP-dependent manner. The inactivation of ycgR
improves swimming and swarming motility of the poorly motile yhjH
mutants of Salmonella enterica serovar Typhimurium UMR1. Therefore,
biochemical and genetic evidence presented here establishes PilZ
as a long sought after c-di-GMP-binding domain and YcgR as a c-di-GMP
receptor affecting motility in enterobacteria.},
url = {http://www.jbc.org/cgi/content/abstract/281/41/30310}
}
@ARTICLE{Ryjenkov2005,
author = {Ryjenkov, Dmitri A. and Tarutina, Marina and Moskvin, Oleg V. and
Gomelsky, Mark},
title = {Cyclic Diguanylate Is a Ubiquitous Signaling Molecule in Bacteria:
Insights into Biochemistry of the GGDEF Protein Domain},
journal = {J. Bacteriol.},
year = {2005},
volume = {187},
pages = {1792--1798},
number = {5},
month = mar,
abstract = {Proteins containing GGDEF domains are encoded in the majority of sequenced
bacterial genomes. In several species, these proteins have been implicated
in biosynthesis of exopolysaccharides, formation of biofilms, establishment
of a sessile lifestyle, surface motility, and regulation of gene
expression. However, biochemical activities of only a few GGDEF domain
proteins have been tested. These proteins were shown to be involved
in either synthesis or hydrolysis of cyclic-bis(3'[->]5') dimeric
GMP (c-di-GMP) or in hydrolysis of cyclic AMP. To investigate specificity
of the GGDEF domains in Bacteria, six GGDEF domain-encoding genes
from randomly chosen representatives of diverse branches of the bacterial
phylogenetic tree, i.e., Thermotoga, Deinococcus-Thermus, Cyanobacteria,
spirochetes, and {alpha} and {gamma} divisions of the Proteobacteria,
were cloned and overexpressed. All recombinant proteins were purified
and found to possess diguanylate cyclase (DGC) activity involved
in c-di-GMP synthesis. The individual GGDEF domains from two proteins
were overexpressed, purified, and shown to possess a low level of
DGC activity. The oligomeric states of full-length proteins and individual
GGDEF domains were similar. This suggests that GGDEF domains are
sufficient to encode DGC activity; however, enzymatic activity is
highly regulated by the adjacent sensory protein domains. It is shown
that DGC activity of the GGDEF domain protein Rrp1 from Borrelia
burgdorferi is strictly dependent on phosphorylation status of its
input receiver domain. This study establishes that majority of GGDEF
domain proteins are c-di-GMP specific, that c-di-GMP synthesis is
a wide-spread phenomenon in Bacteria, and that it is highly regulated.},
url = {http://jb.asm.org/cgi/content/abstract/187/5/1792}
}
@ARTICLE{Rysa2010,
author = {Rysa, Jaana and Tenhunen, Olli and Serpi, Raisa and Soini, Ylermi
and Nemer, Mona and Leskinen, Hanna and Ruskoaho, Heikki},
title = {GATA-4 Is an Angiogenic Survival Factor of the Infarcted Heart},
journal = {Circ Heart Fail},
year = {2010},
volume = {3},
pages = {440--450},
number = {3},
month = may,
abstract = {Background--Recent data suggest that GATA-4 is an antiapoptotic factor
required for adaptive responses and a key regulator of hypertrophy
and hypertrophy-associated genes in the heart. As a leading cause
of chronic heart failure, reversal of postinfarction left ventricular
remodeling represents an important target for therapeutic interventions.
Here, we studied the role of GATA-4 as a mediator of postinfarction
remodeling in rats. Methods and Results--Myocardial infarction, caused
by ligating the left anterior descending coronary artery, significantly
decreased the DNA binding activity of GATA-4 at day 1, whereas at
2 weeks the GATA-4 DNA binding was significantly upregulated. To
determine the functional role of GATA-4, peri-infarct intramyocardial
delivery of adenoviral vector expressing GATA-4 was done before left
anterior descending coronary artery ligation. Hearts treated with
GATA-4 gene transfer exhibited significantly increased ejection fraction
and fractional shortening. Accordingly, infarct size was significantly
reduced. To determine the cardioprotective mechanisms of GATA-4,
myocardial angiogenesis, rate of apoptosis, c-kit+ cardiac stemlike
cells, and genes regulated by GATA-4 were studied. The number of
capillaries and stemlike cells was significantly increased, and decreased
apoptosis was observed. Conclusion--These results indicate that the
reversal of reduced GATA-4 activity prevents adverse postinfarction
remodeling through myocardial angiogenesis, antiapoptosis, and stem
cell recruitment. GATA-4-based gene transfer may represent a novel,
efficient therapeutic approach for heart failure.},
url = {http://circheartfailure.ahajournals.org/cgi/content/abstract/3/3/440}
}
@ARTICLE{Ryschich2006,
author = {Ryschich, Eduard and Lizdenis, Paulius and Ittrich, Carina and Benner,
Axel and Stahl, Simone and Hamann, Alf and Schmidt, Jan and Knolle,
Percy and Arnold, Bernd and Hammerling, Gunter J. and Ganss, Ruth},
title = {Molecular Fingerprinting and Autocrine Growth Regulation of Endothelial
Cells in a Murine Model of Hepatocellular Carcinoma},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {198--211},
number = {1},
month = jan,
abstract = {In a mouse model of hepatocellular carcinogenesis, highly vascularized
tumors develop through two distinct morphologic phases of neovascularization.
We show that increased vascular caliber occurs first, followed by
extensive vessel sprouting in late-stage carcinomas. To define molecular
pathways in tumor neovascularization, endothelial cells were directly
purified from normal liver and advanced tumors. Gene expression profiling
experiments were then designed to identify genes enriched in the
vascular compartment. We report that Cathepsin S is the major protease
specifically overexpressed during vessel sprouting. We also show
that the CC chemokines CCL2 and CCL3 are secreted by neovessels and
stimulate proliferation through their cognate receptors in an autocrine
fashion. This suggests that chemokine signaling represents the most
prominent signaling pathway in tumor-associated endothelial cells
and directly regulates vessel remodeling. Furthermore, high angiogenic
activity is associated with attenuated lymphocyte extravasation and
correlates with expression of the immunomodulatory cytokine interleukin
10. This is the first comprehensive study addressing liver-specific
vascular changes in a murine autochthonous tumor model. These novel
insights into liver angiogenesis infer an environmental control of
neovascularization and have important implications for the design
of antiangiogenic therapies. (Cancer Res 2006; 66(1): 198-211)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/1/198}
}
@ARTICLE{Ryser2011,
author = {Ryser, Stephan and Glauser, Dominique and Vigier, Michelle and Zhang,
Yong and Tachini, Philippe and Schlegel, Werner and Durand, Philippe
and Irminger-Finger, Irmgard},
title = {Gene expression profiling of rat spermatogonia and Sertoli cells
reveals signaling pathways from stem cells to niche and testicular
cancer cells to surrounding stroma},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {29},
number = {1},
abstract = {BACKGROUND:Stem cells and their niches are studied in many systems,
but mammalian germ stem cells (GSC) and their niches are still poorly
understood. In rat testis, spermatogonia and undifferentiated Sertoli
cells proliferate before puberty, but at puberty most spermatogonia
enter spermatogenesis, and Sertoli cells differentiate to support
this program. Thus, pre-pubertal spermatogonia might possess GSC
potential and pre-pubertal Sertoli cells niche functions. We hypothesized
that the different stem cell pools at pre-puberty and maturity provide
a model for the identification of stem cell and niche-specific genes.
We compared the transcript profiles of spermatogonia and Sertoli
cells from pre-pubertal and pubertal rats and examined how these
related to genes expressed in testicular cancers, which might originate
from inappropriate communication between GSCs and Sertoli cells.RESULTS:The
pre-pubertal spermatogonia-specific gene set comprised known stem
cell and spermatogonial stem cell (SSC) markers. Similarly, the pre-pubertal
Sertoli cell-specific gene set comprised known niche gene transcripts.
A large fraction of these specifically enriched transcripts encoded
trans-membrane, extra-cellular, and secreted proteins highlighting
stem cell to niche communication. Comparing selective gene sets established
in this study with published gene expression data of testicular cancers
and their stroma, we identified sets expressed genes shared between
testicular tumors and pre-pubertal spermatogonia, and tumor stroma
and pre-pubertal Sertoli cells with statistic significance.CONCLUSIONS:Our
data suggest that SSC and their niche specifically express complementary
factors for cell communication and that the same factors might be
implicated in the communication between tumor cells and their micro-enviroment
in testicular cancer.},
doi = {10.1186/1471-2164-12-29},
issn = {1471-2164},
pubmedid = {21232125},
url = {http://www.biomedcentral.com/1471-2164/12/29}
}
@ARTICLE{Ryu2011,
author = {Ryu, Moon-Suhn and Langkamp-Henken, Bobbi and Chang, Shou-Mei and
Shankar, Meena N. and Cousins, Robert J.},
title = {Genomic analysis, cytokine expression, and microRNA profiling reveal
biomarkers of human dietary zinc depletion and homeostasis},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {20970-20975},
number = {52},
abstract = {Implementation of zinc interventions for subjects suspected of being
zinc-deficient is a global need, but is limited due to the absence
of reliable biomarkers. To discover molecular signatures of human
zinc deficiency, a combination of transcriptome, cytokine, and microRNA
analyses was applied to a dietary zinc depletion/repletion protocol
with young male human subjects. Concomitant with a decrease in serum
zinc concentration, changes in buccal and blood gene transcripts
related to zinc homeostasis occurred with zinc depletion. Microarray
analyses of whole blood RNA revealed zinc-responsive genes, particularly,
those associated with cell cycle regulation and immunity. Responses
of potential signature genes of dietary zinc depletion were further
assessed by quantitative real-time PCR. The diagnostic properties
of specific serum microRNAs for dietary zinc deficiency were identified
by acute responses to zinc depletion, which were reversible by subsequent
zinc repletion. Depression of immune-stimulated TNF secretion by
blood cells was observed after low zinc consumption and may serve
as a functional biomarker. Our findings introduce numerous novel
candidate biomarkers for dietary zinc status assessment using a variety
of contemporary technologies and which identify changes that occur
prior to or with greater sensitivity than the serum zinc concentration
which represents the current zinc status assessment marker. In addition,
the results of gene network analysis reveal potential clinical outcomes
attributable to suboptimal zinc intake including immune function
defects and predisposition to cancer. These demonstrate through a
controlled depletion/repletion dietary protocol that the illusive
zinc biomarker(s) can be identified and applied to assessment and
intervention strategies.},
doi = {10.1073/pnas.1117207108},
eprint = {http://www.pnas.org/cgi/reprint/108/52/20970.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/52/20970}
}
@ARTICLE{Racz2011,
author = {Rácz, E. and Prens, E.P. and Kant, M. and Florencia, E. and Jaspers,
N.G. and Laman, J.D. and de Ridder, D. and van der Fits, L.},
title = {Narrowband ultraviolet B inhibits innate cytosolic double-stranded
RNA receptors in psoriatic skin and keratinocytes},
journal = {British Journal of Dermatology},
year = {2011},
volume = {164},
pages = {838--847},
number = {4},
abstract = {Summary Background  The mode of action of narrowband ultraviolet
B (NB-UVB) therapy in clearing psoriasis is incompletely understood,
and in vivo studies at the molecular level in patients undergoing
NB-UVB therapy are limited. We previously demonstrated increased
expression and activity of double-stranded RNA (dsRNA) receptors
in psoriasis lesions, and suggested that this enhanced innate signalling
contributed to the maintenance of psoriatic inflammation.Objectives 
We investigated whether NB-UVB affects dsRNA receptor expression
and function in vivo as well as in vitro.Methods  Skin samples
of patients with psoriasis undergoing NB-UVB treatment were analysed
for epidermal messenger RNA (mRNA) expression of the various dsRNA
receptors by microarray and quantitative reverse transcription–polymerase
chain reaction. Primary human keratinocytes were irradiated with
NB-UVB and stimulated with interferon (IFN)-α or IFN-γ, critical
cytokines in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic
acid was used to assess the functional responsiveness of the cells
to dsRNA.Results  NB-UVB therapy of patients with psoriasis resulted
in a significantly reduced mRNA expression of the activating dsRNA
receptors MDA5 (IFIH1) and RIG-I (DDX58). On the other hand, expression
of LGP2 (DHX58), toll-like receptor 3 (TLR3) and PKR (EIF2AK2) was
not affected. In vitro, NB-UVB irradiation completely blocked the
upregulation of four of the dsRNA receptors in primary human keratinocytes
stimulated with IFN-α or IFN-γ, resulting in an attenuated inflammatory
response to dsRNA.Conclusions  Our results show that NB-UVB irradiation
inhibits the local innate inflammatory response to dsRNA, and suggest
a novel mechanism of action of NB-UVB phototherapy in psoriasis.},
doi = {10.1111/j.1365-2133.2010.10169.x},
issn = {1365-2133},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2133.2010.10169.x}
}
@ARTICLE{Rakosy2007,
author = {Rákosy, Zsuzsa and VÃzkeleti, Laura and Ecsedi, Szilvia and Vokó,
Zoltán and Bégány, �gnes and Barok, Márk and Krekk, Zsuzsa and
Gallai, Mónika and Szentirmay, Zoltán and �dány, Róza and Balázs,
Margit},
title = {EGFR gene copy number alterations in primary cutaneous malignant
melanomas are associated with poor prognosis},
journal = {Int. J. Cancer},
year = {2007},
volume = {121},
pages = {1729--1737},
number = {8},
abstract = {Abstract 10.1002/ijc.22928.abs Copy number alterations of the epidermal
growth factor receptor (EGFR) gene have been extensively analyzed
in different cancers, but no data are available for primary malignant
melanoma. The aim of the present study was to simultaneously investigate
the EGFR gene and chromosome 7 copy number alterations in 81 cutaneous
malignant melanomas by interphase FISH and correlate the data with
clinicopathological parameters of patients. EGFR mRNA levels were
detected by Affymetrix GeneChip Human Genome U133 Plus 2.0 expression
arrays for 16 lesions. Both increased gene dosage and chromosome
7 alterations were found in 70% of tumors. Extra EGFR copies were
detected in an additional 10% of samples. Polysomy 7 was associated
with EGFR gene amplification. Significant correlation was found between
EGFR alterations and histological subtypes, tumor thickness, ulceration
and metastases formation. Amplification was significantly higher
in lesions that developed metastases within 2 years after surgical
excision of the primary tumor. Gene copy alterations were associated
with elevated mRNA expression in 77% of lesions when compared to
tumors with disomic EGFR status, the correlation was not directly
proportional to gene copy number. Associations between protein expression
and mRNA levels were even less prominent. In conclusion, our study
indicates that amplification of the EGFR gene and polysomy 7 are
frequent alterations in primary melanomas and are associated with
bad prognosis. Further studies are required to clarify whether melanoma
patients with EGFR alterations can benefit from anti-EGFR therapy.
© 2007 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {EGFR copy number alterations, chromosome 7 polysomy, primary melanoma,
fluorescence in situ hybridization, gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22928}
}
@ARTICLE{Roedder2009,
author = {Rödder, S. and Scherer, A. and Raulf, F. and Berthier, C. C. and
Hertig, A. and Couzi, L. and Durrbach, A. and Rondeau, E. and Marti,
H.-P.},
title = {Renal Allografts with IF/TA Display Distinct Expression Profiles
of Metzincins and Related Genes},
journal = {American Journal of Transplantation},
year = {2009},
volume = {9},
pages = {517--526},
number = {3},
abstract = {Chronic renal allograft injury is often reflected by interstitial
fibrosis (IF) and tubular atrophy (TA) without evidence of specific
etiology. In most instances, IF/TA remains an irreversible disorder,
representing a major cause of long-term allograft loss. As members
of the protease family metzincins and functionally related genes
are involved in fibrotic and sclerotic processes of the extracellular
matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression
and protein level analyses using allograft biopsies with and without
Banff'05 classified IF/TA illustrated their deregulation. Expression
profiles of these genes differentiated IF/TA from Banff'05 classified
Normal biopsies in three independent microarray studies and demonstrated
histological progression of IF/TA I to III. Significant upregulation
of matrix metalloprotease-7 (MMP-7) and thrombospondin-2 (THBS-2)
in IF/TA biopsies and sera was revealed in two independent patient
sets. Furthermore, elevated THBS-2, osteopontin (SPP1) and β-catenin
may play regulatory roles on MMP. Our findings further suggest that
deregulated ECM remodeling and possibly epithelial to mesenchymal
transition (EMT) are implicated in IF/TA of kidney transplants, and
that metzincins and related genes play an important role in these
processes. Profiling of these genes may be used to complement IF/TA
diagnosis and to disclose IF/TA progression in kidney transplant
recipients.},
issn = {1600-6143},
keywords = {Chronic allograft injury, extracellular matrix, IF/TA, matrix metalloproteases,
MMP-7, transcriptomics},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1600-6143.2008.02512.x}
}
@ARTICLE{Roese2012,
author = {Röse, Lars and Schneider, Claudia and Stock, Christine and Zollner,
Thomas M. and Döcke, Wolf-Dietrich},
title = {Extended DNFB-induced contact hypersensitivity models display characteristics
of chronic inflammatory dermatoses},
journal = {Experimental Dermatology},
year = {2012},
volume = {21},
pages = {25--31},
number = {1},
abstract = {Abstract:  Despite recent developments, there is a high medical
need for new treatment options for chronic inflammatory dermatoses
like allergic contact dermatitis (ACD) and psoriasis. Particularly,
more predictive skin inflammation models are required to facilitate
the process of drug discovery. Murine contact hypersensitivity (CHS)
models adequately reflect ACD and are also used to characterize therapeutic
approaches for psoriasis. Using the hapten 2,4-dinitrofluorobenzene
(DNFB), we established new subacute and subchronic DNFB-induced CHS
models in C57BL/6 mice, which more closely reflect the characteristics
of chronic T-cell-dependent inflammatory dermatoses as pronounced
keratinocyte proliferation, strong hypervascularization, immune cell
infiltration and overexpression of T cell and inflammatory cytokines.
For the subacute DNFB model, we demonstrated anti-inflammatory activity
of the glucocorticoid, prednisolone, as well as of neutralization
of TNFα, IL-12/IL-23 or IL-18. In the subchronic DNFB-induced CHS
model, deficiency for MyD88 and IL-12/IL-35 p35 chain but not IL-12/IL-23
p40 chain led to decreased skin inflammation. Furthermore, as exemplified
by the dose-dependently effective therapeutic prednisolone treatment,
the subchronic model allows the continuous therapy of a pre-established
stable contact dermatitis. Altogether, prolonged DNFB-induced mouse
CHS models closely reflect ACD sensitive to glucocorticoids as standard
therapy, reveal a more chronic skin inflammation and are responsive
to cytokine antagonization.},
doi = {10.1111/j.1600-0625.2011.01395.x},
issn = {1600-0625},
keywords = {2,4-dinitrofluorobenzene, allergic contact dermatitis, mouse model},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0625.2011.01395.x}
}
@ARTICLE{Roedningen2008,
author = {Rødningen, Olaug Kristin and Børresen-Dale, Anne-Lise and Alsner,
Jan and Hastie, Trevor and Overgaard, Jens},
title = {Radiation-induced gene expression in human subcutaneous fibroblasts
is predictive of radiation-induced fibrosis},
journal = {Radiotherapy and Oncology},
year = {2008},
volume = {86},
pages = {314--320},
number = {3},
month = mar,
abstract = {Background and purpose Breast cancer patients show a large variation
in normal tissue reactions after ionizing radiation (IR) therapy.
One of the most common long-term adverse effects of ionizing radiotherapy
is radiation-induced fibrosis (RIF), and several attempts have been
made over the last years to develop predictive assays for RIF. Our
aim was to identify basal and radiation-induced transcriptional profiles
in fibroblasts from breast cancer patients that might be related
to the individual risk of RIF in these patients.Materials and methods
Fibroblast cell lines from 31 individuals with variable risk of RIF
(grouped into five classes from low to high risk) were irradiated
with two different schemes: 1 × 3.5 Gy with RNA isolated 2 and 24 h
after irradiation, and a fractionated scheme with 3 × 3.5 Gy in intervals
of 24 h with RNA isolated 2 h after the last dose. RNA was also isolated
from non-treated fibroblasts. Transcriptional differences in basal
and radiation-induced gene expression profiles were investigated
using 15K cDNA microarrays, and results analyzed by both SAM and
PAM.Results Sixty differentially expressed genes were identified
by applying SAM on 10 patients with the highest risk of RIF and the
four patients with the lowest risk of RIF after the fractionated
scheme. The genes were associated with known functions in processes
like apoptosis, extracellular matrix remodelling/cell adhesion, proliferation
and ROS scavenging. A minimum set of 18 genes were identified that
could differentiate high risk from low risk-patients after the fractionated
scheme.Conclusions The classifier of 18 genes may provide basis for
a predictive assay for normal tissue reactions after radiotherapy,
and provide new insight into the molecular mechanisms of RIF.},
booktitle = {Special Issue: Clinical related radiobiology},
issn = {0167-8140},
keywords = {Ionizing radiation, Radiation-induced fibrosis, Gene expression, cDNA
microarray, Fibroblasts, Prediction},
url = {http://www.sciencedirect.com/science/article/B6TBY-4R05HY7-1/2/8789168660473e20dd17e3479f7d8eae}
}
@ARTICLE{Roee2010,
author = {Røe, Oluf Dimitri and Anderssen, Endre and Sandeck, Helmut and Christensen,
Tone and Larsson, Erik and Lundgren, Steinar},
title = {Malignant pleural mesothelioma: Genome-wide expression patterns reflecting
general resistance mechanisms and a proposal of novel targets},
journal = {Lung Cancer},
year = {2010},
volume = {67},
pages = {57--68},
number = {1},
month = jan,
abstract = {Malignant pleural mesothelioma is an asbestos-related multi-resistant
tumour with increasing incidence worldwide. Well-characterized snap-frozen
normal parietal, visceral pleura and mesothelioma samples were analysed
with Affymetrix Human Genome U133 Plus 2.0 GeneChip oligoarray of
38 500 genes. We discovered a close relation between gene profile
and resistance towards topoisomerase poisons, alkylating agents,
antitubulines, antifolates, platinum compounds and radiation therapy.
Target genes of chemo- (e.g. TOP2A, BIRC5/Survivin and proteasome)
and radiotherapy (e.g. BRCA2, FANCA, FANCD2, CCNB1 and RAD50) were
significantly overexpressed. The Fanconi anemia/BRCA2 pathway, responsible
for homologous recombination DNA repair appears as a key pathway
in both chemo- and radio-resistance of mesothelioma. Leukocyte trans-endothelial
migration gene down-regulation could partly explain resistance against
immunological therapies. Gene expression features found in other
resistant cancer types related to DNA repair and replication are
shared by mesothelioma and could represent general features of tumour
resistance. Targeted suppression of some of those key genes and pathways
combined with chemotherapy or radiation could improve the outcome
of mesothelioma therapy. We propose CHEK1, RAD21, FANCD2 and RAN
as new co-targets for mesothelioma treatment. The pro-angiogenic
AGGF1 mRNA and protein was highly overexpressed in all tumours and
may serve as a target for anti-angiogenic treatment. Overexpression
of NQO1 may render mesothelioma sensitive to the novel compound beta-Lapachone.},
issn = {0169-5002},
keywords = {Chemo-resistance, DNA repair, Drug target, Fanconi anemia, Homologous
recombination, Microarray, Radiation resistance},
url = {http://www.sciencedirect.com/science/article/B6T9C-4W3SNDF-2/2/b572fd013287331199b8b65b9802380d}
}
@ARTICLE{Saad2011,
author = {H. El Sheikh Saad and G. Meduri and P. Phrakonkham and R. Bergès
and S. Vacher and M. Djallali and J. Auger and M.C. Canivenc-Lavier
and M. Perrot-Applanat},
title = {Abnormal peripubertal development of the rat mammary gland following
exposure in utero and during lactation to a mixture of genistein
and the food contaminant vinclozolin},
journal = {Reproductive Toxicology},
year = {2011},
volume = {32},
pages = {15 - 25},
number = {1},
abstract = {The impact of early exposure to endocrine disruptor mixtures on mammary
gland development is poorly known. Here, we identify the effects
of a conception to weaning exposure of rats to the phytoestrogen
genistein (G) and/or the antiandrogen vinclozolin (V) at 1 mg/kg-d,
alone or in association. Using several approaches, we found that
G- and GV-exposed rats displayed significantly greater epithelial
branching and proliferation, wider terminal end buds than controls
at PND35, as well as ductal hyperplasia and periductal fibrosis.
Focal branching defects were present in V-exposed rats. An increased
ER and AR expression was observed in G- and GV- as compared to V-exposed
rats at PND35. Surprisingly, a significant number of GV- and to a
lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar
structures at PND50. Thus, gestational and lactational exposure to
low doses of genistein plus vinclozolin may seriously affect peripubertal
development of the rat mammary gland.},
doi = {10.1016/j.reprotox.2011.03.001},
issn = {0890-6238},
keywords = {Endocrine disruption},
url = {http://www.sciencedirect.com/science/article/pii/S089062381100075X}
}
@ARTICLE{Saal2007,
author = {Saal, Lao H. and Johansson, Peter and Holm, Karolina and Gruvberger-Saal,
Sofia K. and She, Qing-Bai and Maurer, Matthew and Koujak, Susan
and Ferrando, Adolfo A. and Malmstrom, Per and Memeo, Lorenzo and
Isola, Jorma and Bendahl, Par-Ola and Rosen, Neal and Hibshoosh,
Hanina and Ringner, Markus and Borg, Ake and Parsons, Ramon},
title = {Poor prognosis in carcinoma is associated with a gene expression
signature of aberrant PTEN tumor suppressor pathway activity},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {7564--7569},
number = {18},
month = may,
abstract = {Pathway-specific therapy is the future of cancer management. The oncogenic
phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated
in solid tumors; however, currently, no reliable test for PI3K pathway
activation exists for human tumors. Taking advantage of the observation
that loss of PTEN, the negative regulator of PI3K, results in robust
activation of this pathway, we developed and validated a microarray
gene expression signature for immunohistochemistry (IHC)-detectable
PTEN loss in breast cancer (BC). The most significant signature gene
was PTEN itself, indicating that PTEN mRNA levels are the primary
determinant of PTEN protein levels in BC. Some PTEN IHC-positive
BCs exhibited the signature of PTEN loss, which was associated to
moderately reduced PTEN mRNA levels cooperating with specific types
of PIK3CA mutations and/or amplification of HER2. This demonstrates
that the signature is more sensitive than PTEN IHC for identifying
tumors with pathway activation. In independent data sets of breast,
prostate, and bladder carcinoma, prediction of pathway activity by
the signature correlated significantly to poor patient outcome. Stathmin,
encoded by the signature gene STMN1, was an accurate IHC marker of
the signature and had prognostic significance in BC. Stathmin was
also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature
or its components such as stathmin may be clinically useful tests
for stratification of patients for anti-PI3K pathway therapy and
monitoring therapeutic efficacy. This study indicates that aberrant
PI3K pathway signaling is strongly associated with metastasis and
poor survival across carcinoma types, highlighting the enormous potential
impact on patient survival that pathway inhibition could achieve.},
url = {http://www.pnas.org/cgi/content/abstract/104/18/7564}
}
@ARTICLE{Saama2006,
author = {Saama, Peter M. and Patel, Osman V. and Bettegowda, Anilkumar and
Ireland, James J. and Smith, George W.},
title = {Novel algorithm for transcriptome analysis},
journal = {Physiol Genomics},
year = {2006},
volume = {28},
pages = {62--66},
number = {1},
month = dec,
abstract = {A growing body of evidence implicates the oocyte as a key regulator
of ovarian folliculogenesis and early embryonic development. We have
screened bovine cDNA microarrays (containing expressed sequence tags
representing >15,000 unique genes) with Cy3- and Cy5-labeled cDNA
derived from bovine oocyte samples collected at two different stages
of meiotic maturation (germinal vesicle vs. metaphase II; n = 3 samples
per group). Here, we present a novel data analysis approach that
uses all available information from above experiments to obtain and
index the transcriptome of bovine oocytes and changes in transcriptome
composition in response to meiotic maturation. Signal intensities
(Fg) for all housekeeping genes were omitted prior to analysis. A
local threshold for gene expression was computed as background intensity
(Bg) plus 2 times the standard deviation of background and foreground
signals. Within each array, data were normalized by the LOWESS procedure.
Subsequently, a two-stage mixed model was fitted to remove systematic
variations. In the first stage, the response was the LOWESS normalized
Fg with treatment as a fixed effect. In stage 2, the residuals from
stage 1 were analyzed in a gene-specific model that included treatment
group and spots nested within patch and array. A test for the difference
between least squares means for the treatment effect was performed.
A false discovery rate (FDR) adjustment on the p values for the difference
was carried out. This novel algorithm was compared with approaches
that ignore the FDR and the threshold described herein and stark
differences obtained.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/28/1/62}
}
@ARTICLE{Saavedra2005,
author = {Saavedra, Ana and Baltazar, Graça and Carvalho, Caetana M. and Duarte,
Emília P.},
title = {GDNF modulates HO-1 expression in substantia nigra postnatal cell
cultures},
journal = {Free Radical Biology and Medicine},
year = {2005},
volume = {39},
pages = {1611--1619},
number = {12},
month = dec,
abstract = {Heme oxygenase-1 (HO-1) has been strongly highlighted because of its
induction in many cell types by toxic stimuli, including oxidative
stress. The intense HO-1 immunostaining in the substantia nigra of
Parkinson disease (PD) patients suggests its involvement in the pathogenesis
of this neurodegenerative disease. In this work we investigated HO-1
expression in rat substantia nigra postnatal cell cultures under
conditions mimicking dopamine toxicity and its modulation by glial
cell line-derived neurotrophic factor (GDNF), a potent neuroprotective
factor for dopaminergic neurons. In neuron-glia cultures, we found
that H2O2, a product of dopamine metabolism, or l-3,4-dihydroxyphenylalanine
(l-DOPA), the dopamine precursor used in the therapy of PD, induced
a fast up-regulation of HO-1 mRNA and protein levels, followed by
a secondary down-regulation. H2O2 and l-DOPA also increased HO-1
expression in astrocyte cultures, but with a delayed time course
in H2O2-treated cultures. HO-1 expression was decreased in neuron-glia
cultures under conditions under which GDNF up-regulation was observed.
Because exogenously applied GDNF prevented HO-1 up-regulation in
cultures treated with H2O2 or l-DOPA, and antibody neutralization
of GDNF prevented the secondary HO-1 down-regulation observed in
neuron-glia cultures, we propose that GDNF negatively modulates HO-1
expression induced by oxidative stress. To our knowledge, this is
the first report showing the modulation of HO-1 expression by GDNF.},
issn = {0891-5849},
keywords = {Astrocytes, Dopaminergic neurons, Glial cell line-derived neurotrophic
factor, Heme oxygenase-1, Oxidative stress, Parkinson disease, Free
radicals},
url = {http://www.sciencedirect.com/science/article/B6T38-4GY83GS-1/2/965b3339b80f3bb715ddd831da2fcfe7}
}
@ARTICLE{Saavedra2007,
author = {Saavedra, Ana and Baltazar, Graça and Duarte, Emília P.},
title = {Interleukin-1[beta] mediates GDNF up-regulation upon dopaminergic
injury in ventral midbrain cell cultures},
journal = {Neurobiology of Disease},
year = {2007},
volume = {25},
pages = {92--104},
number = {1},
month = jan,
abstract = {We recently proposed the involvement of diffusible modulators in signalling
astrocytes to increase glial cell line-derived neurotrophic factor
(GDNF) expression after selective dopaminergic injury by H2O2 or
l-DOPA. Here we report that interleukin-1[beta] (IL-1[beta]) is involved
in this crosstalk between injured neurons and astrocytes. IL-1[beta]
was detected only in the media from challenged neuron-glia cultures.
Exogenous IL-1[beta] did not change GDNF protein levels in astrocyte
cultures, and diminished GDNF levels in neuron-glia cultures. This
decrease was not due to cell loss, as assessed by the MTT assay and
immunocytochemistry. Neither H2O2 nor l-DOPA induced microglia proliferation
or appeared to change its activation state. The IL-1 receptor antagonist
(IL-1ra) prevented GDNF up-regulation in challenged cultures, showing
that IL-1[beta] is involved in the signalling between injured neurons
and astrocytes. Since IL-1ra decreased the number of dopaminergic
neurons in H2O2-treated cultures, we propose that IL-1 has a neuroprotective
role in this system involving GDNF up-regulation.},
issn = {0969-9961},
keywords = {Astrocytes, Crosstalk, Dopaminergic neurons, GDNF, IL-1[beta], Injury,
Microglia, Neuroprotection},
url = {http://www.sciencedirect.com/science/article/B6WNK-4M21SWS-3/2/7fdd35b177b4419ba34c864915a9fcb5}
}
@ARTICLE{Saavedra2006,
author = {Saavedra, Ana and Baltazar, Graça and Santos, Paulo and Carvalho,
Caetana M. and Duarte, Emília P.},
title = {Selective injury to dopaminergic neurons up-regulates GDNF in substantia
nigra postnatal cell cultures: Role of neuron-glia crosstalk},
journal = {Neurobiology of Disease},
year = {2006},
volume = {23},
pages = {533--542},
number = {3},
month = sep,
abstract = {The effect of selective injury to dopaminergic neurons on the expression
of glial cell line-derived neurotrophic factor (GDNF) was examined
in substantia nigra cell cultures. H2O2, mimicking increased oxidative
stress, or l-DOPA, the main symptomatic treatment for Parkinson's
disease, increased GDNF mRNA and protein levels in a time-dependent
mode in neuron-glia mixed cultures. The concentration dependence
indicated that mild, but not extensive, injury induced GDNF up-regulation.
GDNF neutralization with an antibody decreased dopaminergic cell
viability in H2O2-treated cultures, showing that up-regulation of
GDNF was protecting dopaminergic neurons. Neither H2O2 nor l-DOPA
directly affected GDNF expression in astrocyte cultures, but conditioned
media from challenged mixed cultures increased GDNF mRNA and protein
levels in astrocyte cultures, indicating that GDNF up-regulation
was mediated by neuronal factors. Since pretreatment with 6-OHDA
completely abolished H2O2-induced GDNF up-regulation, we propose
that GDNF up-regulation is triggered by failing dopaminergic neurons
that signal astrocytes to increase GDNF expression.},
issn = {0969-9961},
keywords = {Astrocytes, Crosstalk, Dopaminergic neurons, GDNF, Injury, Neuroprotection,
Parkinson's disease, Substantia nigra},
url = {http://www.sciencedirect.com/science/article/B6WNK-4K5HWBN-8/2/dec052b91f0855f3ec23bdc152d851d4}
}
@ARTICLE{Saavedra-Rodriguez2009,
author = {Saavedra-Rodriguez, Lorena and Vazquez, Adrinel and Ortiz-Zuazaga,
Humberto G. and Chorna, Nataliya E. and Gonzalez, Fernando A. and
Andres, Lissette and Rodriguez, Karen and Ramirez, Fernando and Rodriguez,
Alan and de Ortiz, Sandra Pena},
title = {Identification of Flap Structure-Specific Endonuclease 1 as a Factor
Involved in Long-Term Memory Formation of Aversive Learning},
journal = {J. Neurosci.},
year = {2009},
volume = {29},
pages = {5726--5737},
number = {18},
month = may,
abstract = {We previously proposed that DNA recombination/repair processes play
a role in memory formation. Here, we examined the possible role of
the fen-1 gene, encoding a flap structure-specific endonuclease,
in memory consolidation of conditioned taste aversion (CTA). Quantitative
real-time PCR showed that amygdalar fen-1 mRNA induction was associated
to the central processing of the illness experience related to CTA
and to CTA itself, but not to the central processing resulting from
the presentation of a novel flavor. CTA also increased expression
of the Fen-1 protein in the amygdala, but not the insular cortex.
In addition, double immunofluorescence analyses showed that amygdalar
Fen-1 expression is mostly localized within neurons. Importantly,
functional studies demonstrated that amygdalar antisense knockdown
of fen-1 expression impaired consolidation, but not short-term memory,
of CTA. Overall, these studies define the fen-1 endonuclease as a
new DNA recombination/repair factor involved in the formation of
long-term memories.},
url = {http://www.jneurosci.org/cgi/content/abstract/29/18/5726}
}
@ARTICLE{Sabariego2011,
author = {Marta Sabariego and M. José Gómez and Ignacio Morón and Carmen
Torres and Alberto Fernández-Teruel and Adolfo Tobeña and Toni
Cañete and José A. MartÃnez-Conejero and José A. Horcajadas and
Francisco J. Esteban},
title = {Differential gene expression between inbred Roman high- (RHA-I) and
low- (RLA-I) avoidance rats},
journal = {Neuroscience Letters},
year = {2011},
volume = {504},
pages = {265 - 270},
number = {3},
abstract = {Microarray technology was used to explore differences in brain gene
expression under basal conditions in two strains of psychogenetically
selected rats which differ in anxiety/stress responses, the inbred
Roman High-(RHA-I) and Roman Low-(RLA-I) Avoidance rats. Microarray
analysis detected 14 up-regulated and 24 down-regulated genes in
RLA-I vs. RHA-I rats functionally related to neurobiological processes.
The differentially expressed genes CAMKK2, CRHBP, EPHX2, HOMER3,
NDN, PRL and RPL6 were selected for microarray validation using qRT-PCR.
EPHX2, CAMKK2 (both up-regulated in RLA-I vs. RHA-I rats) and HOMER3
(down-regulated in RLA-I vs. RHA-I rats) showed a similar tendency
and fold-change both in microarray and RT-PCR analyses; PRL (up-regulated
in RLA-I vs. RHA-I rats), CRHBP and RPL6 (both down-regulated in
RLA-I vs. RHA-I animals) showed a similar tendency but a different
order of magnitude of change among experiments; finally, NDN was
validated neither in tendency nor in magnitude of change.},
doi = {10.1016/j.neulet.2011.09.044},
issn = {0304-3940},
keywords = {Anxiety},
url = {http://www.sciencedirect.com/science/article/pii/S0304394011013292}
}
@ARTICLE{Sabater2010,
author = {Sabater, Monica and Moreno-Navarrete, Jose M. and Jose Ortega, Francisco
and Pardo, Gerard and Salvador, Javier and Ricart, Wifredo and Fruhbeck,
Gema and Fernandez-Real, Jose Manuel},
title = {Circulating Pigment Epithelium-Derived Factor Levels Are Associated
with Insulin Resistance and Decrease after Weight Loss},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {4720--4728},
number = {10},
month = oct,
abstract = {Objective: We aimed to study circulating pigment epithelium-derived
factor (PEDF) in vivo in association with insulin resistance and
in vitro in human adipocytes. Methods: Circulating PEDF (ELISA) and
metabolic profile were assessed in 125 Caucasian men. PEDF levels
were also assessed in an independent cohort of subjects (n = 33)
to study the effects of changing insulin action. PEDF gene expression
and secretion were measured during differentiation of human preadipocytes.
Results: In all subjects, PEDF was positively associated with body
mass index (r = 0.326; P < 0.0001), waist-to-hip ratio (r = 0.380;
P < 0.0001), HbA1c, and fasting triglycerides and negatively with
insulin sensitivity (r = -0.320; P < 0.0001). PEDF levels were significantly
increased in subjects with altered glucose tolerance and type 2 diabetes.
Of the inflammatory markers measured, PEDF levels were positively
associated with serum soluble TNF-{alpha} receptor 1 and IL-10 in
obese subjects. Interestingly, weight loss led to significantly decreased
PEDF concentration from 34.8 {+/-} 19.3 to 22.5 {+/-} 14.2 {micro}g/ml
(P < 0.0001). Multiple linear regression analyses revealed that insulin
sensitivity contributed independently to explain 14% of the variance
in PEDF levels after controlling for the effects of body mass index,
age, and log fasting triglycerides. Differences in PEDF observed
after weight loss were related to changes in obesity, insulin resistance,
and blood pressure measures. PEDF gene expression and secretion increased
during differentiation of human preadipocytes. Conclusion: Circulating
PEDF is associated with insulin sensitivity. The findings show, for
the first time in humans, that PEDF concentrations decrease significantly
after weight loss in association with blood pressure. PEDF seems
to be involved in human adipocyte biology.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/10/4720}
}
@ARTICLE{Sabatier2011,
author = {Sabatier, Renaud and Finetti, Pascal and Cervera, Nathalie and Tallet,
Agnes and Benchalal, Mohamed and Houvenaeghel, Gilles and Jacquemier,
Jocelyne and Birnbaum, Daniel and Bertucci, Francois},
title = {Gene Expression Profiling and its Utility in Prediction of Local
Relapse after Breast-conserving Therapy in Early Breast Cancer},
journal = {Cancer Genomics Proteomics},
year = {2011},
volume = {8},
pages = {199-209},
number = {4},
abstract = {Background: Local relapse (LR) after breast-conserving therapy (BCT)
is not accurately predicted by histological/clinical factors. Gene
expression profiling was used here to discover LR-associated transcriptional
alterations. Materials and Methods: Gene expression profiling was
carried out of 81 early breast carcinomas obtained from 30 patients
who developed a LR (LR+) after BCT and 51 who did not (LR-). LR+
and LR- samples were matched for known LR risk features. Results:
LR was not associated with a given molecular subtype. Supervised
analysis identified a 212-gene signature, which was not validated
in independent tumors. No gene set or biological pathway was differentially
expressed between LR+ and LR- groups. Twelve published prognostic
expression signatures failed to distinguish these groups of carcinomas.
The gene expression profiles of 9 cases of LR and the corresponding
primary tumors were very similar despite the delivery of radiotherapy.
Conclusion: In this series, the onset of LR was not predicted by
gene expression alterations.},
eprint = {http://cgp.iiarjournals.org/cgi/reprint/8/4/199.pdf},
url = {http://cgp.iiarjournals.org/cgi/content/abstract/8/4/199}
}
@ARTICLE{Sabatini2007,
author = {Sabatini, Michael J. and Ebert, Philip and Lewis, David A. and Levitt,
Pat and Cameron, Judy L. and Mirnics, Karoly},
title = {Amygdala Gene Expression Correlates of Social Behavior in Monkeys
Experiencing Maternal Separation},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {3295--3304},
number = {12},
month = mar,
abstract = {Children exposed to early parental loss from death or separation carry
a greater risk for developing future psychiatric illnesses, such
as major depression and anxiety. Monkeys experiencing maternal separation
at 1 week of age show fewer social behaviors and an increase in self-comforting
behaviors (e.g., thumb sucking) over development, whereas in contrast,
monkeys experiencing maternal separation at 1 month of age show increased
seeking of social comfort later in life. We sought to identify neural
systems that may underlie these stress-induced behavioral changes
by examining changes in mRNA content in amygdala tissue collected
from 1 week separated, 1 month separated, and maternally reared infants
at 3 months of age. mRNA from the right medial temporal lobe, primarily
the amygdala, was analyzed using Affymetrix U133A 2.0 arrays. One
gene, guanylate cyclase 1 {alpha} 3 (GUCY1A3), showed differential
expression between the 1 week and maternally reared groups and the
1 week and 1 month groups; these changes were confirmed by in situ
hybridization. The expression of this gene was positively correlated
with acute social-comforting behavior (r = 0.923; p = 0.001) and
longer-term close social behavior (r = 0.708; p = 0.015) and negatively
correlated with self-comforting behaviors (r = -0.88; p < 0.001).
Additional in situ hybridization studies of GUCY1A3 in normal monkeys
showed that this gene is expressed at adult levels by 1 week of age
and that its expression is greater in the amygdala than all other
brain areas examined. We conclude that GUCY1A3 may contribute to
the altered behavioral phenotypes that are differentially displayed
depending on the age at which macaque infants experience an early-life
stress.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/12/3295}
}
@ARTICLE{Sabatino2008,
author = {Sabatino, Marianna and Zhao, Yingdong and Voiculescu, Sonia and Monaco,
Alessandro and Robbins, Paul and Karai, Laszlo and Nickoloff, Brian
J. and Maio, Michele and Selleri, Silvia and Marincola, Francesco
M. and Wang, Ena},
title = {Conservation of Genetic Alterations in Recurrent Melanoma Supports
the Melanoma Stem Cell Hypothesis},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {122--131},
number = {1},
month = jan,
abstract = {It is generally accepted that human cancers derive from a mutated
single cell. However, the genetic steps characterizing various stages
of progression remain unclear. Studying a unique case of metastatic
melanoma, we observed that cell lines derived from metachronous metastases
arising over a decade retained a central core of genetic stability
in spite of divergent phenotypes. In the present study, we expanded
our previous observations comparing these autologous cell lines of
clonal derivation with allogeneic ones and correlated array comparative
genomic hybridization (aCGH) with gene expression profiling to determine
their relative contribution to the dynamics of disease progression.
aCGH and gene expression profiling were performed on autologous cell
lines and allogeneic melanoma cell lines originating from other patients.
A striking correlation existed between total extent of genetic imbalances,
global transcriptional patterns, and cellular phenotypes. They did
not follow a strict temporal progression but stemmed independently
at various time points from a central core of genetic stability best
explained according to the cancer stem cell hypothesis. Although
their contribution was intertwined, genomic imbalances detectable
by aCGH contributed only 25% of the transcriptional traits determining
autologous tumor distinctiveness. Our study provides important insights
about the dynamics of cancer progression and supports the development
of targeted anticancer therapies aimed against stable genetic factors
that are maintained throughout the end stage of disease. [Cancer
Res 2008;68(1):122-31]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/1/122}
}
@ARTICLE{Sabbagh2006,
author = {Sabbagh, Fadi and Lecerf, Florence and Maurois, Pierre and Bac, Pierre
and German-Fattal, Michèle},
title = {Allogeneic activation is attenuated in a model of mouse lung perfused
with magnesium-deficient blood},
journal = {Transplant Immunology},
year = {2006},
volume = {16},
pages = {200--207},
number = {3-4},
month = nov,
abstract = {Hypomagnesemia, which is frequently observed in patients treated with
calcineurin inhibitors to prevent rejection after allogeneic transplantation,
has been associated with a faster rate of decline in allograft function.
The effect of hypomagnesemia on lung allograft has not been reported
yet. In our model of isolated mouse lung, we have evaluated the early
effects of allogeneic lung perfusion with blood from magnesium (Mg)-deficient
mice for 3 h on lung activation and remodelling, compared to isogeneic
perfusion. Hypomagnesemia (0.21 ± 0.07 mmol Mg2+/l) was observed
in blood from Mg-deficient mice, but no inflammatory pattern. The
mRNA level of the intercellular adhesion molecule (ICAM)-1, but neither
of the vascular cell adhesion molecule (VCAM)-1, nor of the cytokines
tumor necrosis factor (TNF)[alpha] and interleukin (IL)-2, was enhanced
(p < 0.05). Although caspase-3 mRNA was transiently enhanced, no
apoptotic cells were evidenced in lung tissues even after 3 h. Using
cDNA array, we found that the genes encoding RANKL, RANK, TNFR2,
NFATX, IL-1R2, IL-6R gp130, SOCS3, PDGFRB, P63, CSF3R, CXCL1, CXCL5,
CX3CL1, CSF1, which are involved in inflammation and apoptosis regulation,
were markedly up-regulated in allogeneic conditions. Our results
support a limited allogeneic activation and an early stage of the
inflammatory process in lung, at the time of inflammatory cell recruitment
without lung tissue remodelling, as a result of hypomagnesemia. These
findings suggest that cyclosporine-related hypomagnesemia, observed
in most of the transplanted patients, does not constitute an additional
risk for lung allograft outcome.},
issn = {0966-3274},
keywords = {Gene expression, Inflammation, Hypomagnesemia, Isolated mouse lung,
Allogeneic perfusion},
url = {http://www.sciencedirect.com/science/article/B6W6V-4M1KRC3-1/2/9776daf8f0c5cf5cee69f3b9083c2feb}
}
@ARTICLE{Sabbah2011,
author = {Sabbah, Michele and Prunier, Celine and Ferrand, Nathalie and Megalophonos,
Virginie and Lambein, Kathleen and De Wever, Olivier and Nazaret,
Nicolas and Lachuer, Joel and Dumont, Sylvie and Redeuilh, Gerard},
title = {CCN5, a Novel Transcriptional Repressor of the Transforming Growth
Factor {beta} Signaling Pathway},
journal = {Mol. Cell. Biol.},
year = {2011},
volume = {31},
pages = {1459--1469},
number = {7},
month = apr,
abstract = {CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich
61/nephroblastoma overexpressed) family and was identified as an
estrogen-inducible gene in estrogen receptor-positive cell lines.
However, the role of CCN5 in breast carcinogenesis remains unclear.
We report here that the CCN5 protein is localized mostly in the cytoplasm
and in part in the nucleus of human tumor breast tissue. Using a
heterologous transcription assay, we demonstrate that CCN5 can act
as a transcriptional repressor presumably through association with
histone deacetylase 1 (HDAC1). Microarray gene expression analysis
showed that CCN5 represses expression of genes associated with epithelial-mesenchymal
transition (EMT) as well as expression of key components of the transforming
growth factor {beta} (TGF-{beta}) signaling pathway, prominent among
them TGF-{beta}RII receptor. We show that CCN5 is recruited to the
TGF-{beta}RII promoter, thereby providing a mechanism by which CCN5
restricts transcription of the TGF-{beta}RII gene. Consistent with
this finding, CCN5, we found, functions to suppress TGF-{beta}-induced
transcriptional responses and invasion that is concomitant with EMT.
Thus, our data uncovered CCN5 as a novel transcriptional repressor
that plays an important role in regulating tumor progression functioning,
at least in part, by inhibiting the expression of genes involved
in the TGF-{beta} signaling cascade that is known to promote EMT.},
comment = {10.1128/MCB.01316-10},
url = {http://mcb.asm.org/cgi/content/abstract/31/7/1459}
}
@ARTICLE{Sabino2011,
author = {Gregory J. Sabino and Sonya J. Hwang and Shane C. McAllister and
Patricio Mena and Martha B. Furie},
title = {Interferon-γ Influences the Composition of Leukocytic Infiltrates
in Murine Lyme Carditis},
journal = {The American Journal of Pathology},
year = {2011},
volume = {179},
pages = {1917 - 1928},
number = {4},
abstract = {Interferon (IFN)-γ is present in lesions of patients with Lyme disease
and positively correlates with the severity of manifestations. To
investigate the role of IFNγ in the development of Lyme carditis,
wild-type and IFNγ-deficient C57BL/6 mice were infected with the
causative bacterium, Borrelia burgdorferi. Histological analysis
revealed no change in the severity of carditis between wild-type
and IFNγ-deficient mice at 14, 21, 25, and 28 days after infection.
However, a distinct shift in the types of leukocytes within the hearts
of IFNγ-deficient mice was observed at 25 days. In the absence of
IFNγ, the number of neutrophils in the heart was increased, whereas
the number of T lymphocytes was decreased. Bacterial loads within
hearts were the same as in wild-type mice. Macrophages secrete chemokines
that recruit immune cells, which could contribute to the accumulation
of leukocytes in murine Lyme carditis. The ability of IFNγ and B.
burgdorferi to activate murine macrophages was examined, and the
two stimuli synergistically induced chemoattractants for mononuclear
cells (ie, CXCL9, CXCL10, CXCL11, CXCL16, and CCL12) and decreased
those for neutrophils (ie, CXCL1, CXCL2, and CXCL3). IFNγ and B.
burgdorferi also synergistically enhanced secretion of CXCL9 and
CXCL10 by murine cardiac endothelial cells. These results indicate
that IFNγ influences the composition of inflammatory infiltrates
in Lyme carditis by promoting the accumulation of leukocytes associated
with chronic inflammation and suppressing that of cells that typify
acute inflammation.},
doi = {10.1016/j.ajpath.2011.06.029},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011006481}
}
@ARTICLE{Sabo2008,
author = {Sabo, Edmond and Meitner, Patricia A. and Tavares, Rosemarie and
Corless, Christopher L. and Lauwers, Gregory Y. and Moss, Steven
F. and Resnick, Murray B.},
title = {Expression Analysis of Barrett's Esophagus-Associated High-Grade
Dysplasia in Laser Capture Microdissected Archival Tissue},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6440--6448},
number = {20},
month = oct,
abstract = {Purpose: Identifying genes differentially expressed in nondysplastic
BE (NDBE) from those expressed in high-grade dysplasia (HGD) should
be of value in improving our understanding of this transition and
may yield new diagnostic and/or prognostic markers. The aim of this
study was to determine the differential transcriptome of HGD compared
with NDBE through gene microarray analysis of epithelial cells microdissected
from archival tissue specimens. Experimental Design: Laser capture
microdissection was used to isolate epithelial cells from adjacent
inflammatory and stromal cells. Epithelial mRNA was extracted from
areas of NDBE and HGD in matched biopsies from 11 patients. mRNA
was reverse transcribed and applied on Affymetrix cDNA microarray
chips customized for formalin-exposed tissue. For a subset of these
genes, differential gene expression was confirmed by real-time PCR
and immunohistochemistry. Results: There were 131 genes overexpressed
by at least 2.5-fold in HGD versus NDBE and 16 genes that were underexpressed
by at least 2.5-fold. Among the overexpressed genes are several previously
shown to be increased in the neoplastic progression of BE, as well
as novel genes such as lipocalin-2, S100A9, matrix metallopeptidase
12, secernin 1, and topoisomerase II{alpha}. Genes decreased in dysplastic
epithelium include MUC5AC, trefoil factor 1 (TFF1), meprin A, and
CD13. Real-time PCR validated the changes in expression in 24 of
28 selected genes. Immunohistochemistry confirmed increased protein
expression for topoisomerase II{alpha}, S100A9, and lipocalin-2 and
decreased expression of TFF1 across the spectrum of BE-associated
dysplasia from NDBE through adenocarcinoma. Conclusions: This is
the first study to identify epithelial genes differentially expressed
in HGD versus NDBE in matched patient samples. The genes identified
include several previously implicated in the pathogenesis of BE-associated
dysplasia and new candidates for further investigation.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/20/6440}
}
@ARTICLE{Sabo-Attwood2005,
author = {Sabo-Attwood, Tara and Ramos-Nino, Maria and Bond, Jeffrey and Butnor,
Kelly J. and Heintz, Nicholas and Gruber, Achim D. and Steele, Chad
and Taatjes, Douglas J. and Vacek, Pamela and Mossman, Brooke T.},
title = {Gene Expression Profiles Reveal Increased mClca3 (Gob5) Expression
and Mucin Production in a Murine Model of Asbestos-Induced Fibrogenesis},
journal = {Am. J. Pathol.},
year = {2005},
volume = {167},
pages = {1243--1256},
number = {5},
month = nov,
abstract = {To elucidate genes important in development or repair of asbestos-induced
lung diseases, gene expression was examined in mice after inhalation
of chrysotile asbestos for 3, 9, and 40 days. We identified changes
in the expression of genes linked to proliferation (cyclin B2, CDC20,
and CDC28 protein kinase regulatory subunit 2), inflammation (CCL9,
CCL6, complement component 1, chitinase3-like 3, TNF superfamily
member 10, and IL-1B), and matrix remodeling (MMP12, MMP3, integrin
{alpha}X, and cathepsins K, Z, B, and S). The most highly induced
gene at all time points was mclca3 (gob5), a putative calcium-activated
chloride channel involved in the regulation of mucus production and/or
secretion. Using histochemistry, we demonstrated accumulation of
mucus and increased mClca3 protein in the bronchiolar epithelium
of asbestos-exposed mice at all time points but peaking at 9 days.
Cytokine levels (interleukin-1{beta}, interleukin-4, interleukin-6)
in bronchoalveolar lavage fluid also increased at 9 days, suggesting
Th2-mediated immunity may play a role in asbestos-induced mucus production.
In contrast, levels of cathepsin K, a potent elastase, increased
between 3 and 40 days at both the mRNA and protein levels, localizing
primarily in CD45-positive leukocytes and interstitial cells. Identification
of genes involved in lung injury and remodeling after asbestos exposure
could aid in defining mechanisms of airborne particulate-induced
disease and in developing therapeutic strategies.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/167/5/1243}
}
@ARTICLE{Sabour2011,
author = {Sabour, Davood and Arauzo-Bravo, Marcos J. and Hubner, Karin and
Ko, Kinarm and Greber, Boris and Gentile, Luca and Stehling, Martin
and Scholer, Hans R.},
title = {Identification of genes specific to mouse primordial germ cells through
dynamic global gene expression},
journal = {Hum. Mol. Genet.},
year = {2011},
volume = {20},
pages = {115--125},
number = {1},
month = jan,
abstract = {Molecular mechanisms underlying the commitment of cells to the germ
cell lineage during mammalian embryogenesis remain poorly understood
due to the limited availability of cellular materials to conduct
in vitro analyses. Although primordial germ cells (PGCs)--precursors
to germ cells--have been generated from embryonic stem cells (ESCs)--pluripotent
stem cells derived from the inner cell mass of the blastocyst of
the early embryo in vitro--the simultaneous expression of cell surface
receptors and transcription factors complicates the detection of
PGCs. To date, only a few genes that mark the onset of germ cell
commitment in the epiblast--the outer layer of cells of the embryo--including
tissue non-specific alkaline phosphatase (TNAP), Blimp1, Stella and
Fragilis--have been used with some success to detect PGC formation
in in vitro model systems. Here, we identified 11 genes (three of
which are novel) that are specifically expressed in male and female
fetal germ cells, both in vivo and in vitro, but are not expressed
in ESCs. Expression of these genes allows us to distinguish committed
germ cells from undifferentiated pluripotent cell populations, a
prerequisite for the successful derivation of germ cells and gametes
in vitro.},
comment = {10.1093/hmg/ddq450},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/20/1/115}
}
@ARTICLE{Sachdeva2009,
author = {Sachdeva, Mira M. and Claiborn, Kathryn C. and Khoo, Cynthia and
Yang, Juxiang and Groff, David N. and Mirmira, Raghavendra G. and
Stoffers, Doris A.},
title = {Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER
stress},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {19090--19095},
number = {45},
month = nov,
abstract = {Type 2 diabetes mellitus (T2DM) results from pancreatic {beta} cell
failure in the setting of insulin resistance. Heterozygous mutations
in the gene encoding the {beta} cell transcription factor pancreatic
duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity
onset diabetes of the young (MODY4), and low levels of Pdx1 accompany
{beta} cell dysfunction in experimental models of glucotoxicity and
diabetes. Here, we find that Pdx1 is required for compensatory {beta}
cell mass expansion in response to diet-induced insulin resistance
through its roles in promoting {beta} cell survival and compensatory
hypertrophy. Pdx1-deficient {beta} cells show evidence of endoplasmic
reticulum (ER) stress both in the complex metabolic milieu of high-fat
feeding as well as in the setting of acutely reduced Pdx1 expression
in the Min6 mouse insulinoma cell line. Further, Pdx1 deficiency
enhances {beta} cell susceptibility to ER stress-associated apoptosis.
The results of high throughput expression microarray and chromatin
occupancy analyses reveal that Pdx1 regulates a broad array of genes
involved in diverse functions of the ER, including proper disulfide
bond formation, protein folding, and the unfolded protein response.
These findings suggest that Pdx1 deficiency leads to a failure of
{beta} cell compensation for insulin resistance at least in part
by impairing critical functions of the ER.},
url = {http://www.pnas.org/cgi/content/abstract/106/45/19090}
}
@ARTICLE{Sacks2011,
author = {Peter G. Sacks and Zhong-Lin Zhao and Wieslawa Kosinska and Kenneth
E. Fleisher and Terry Gordon and Joseph B. Guttenplan},
title = {Concentration dependent effects of tobacco particulates from different
types of cigarettes on expression of drug metabolizing proteins,
and benzo(a)pyrene metabolism in primary normal human oral epithelial
cells},
journal = {Food and Chemical Toxicology},
year = {2011},
volume = {49},
pages = {2348 - 2355},
number = {9},
abstract = {The ability of tobacco smoke (TS) to modulate phase I and II enzymes
and affect metabolism of tobacco carcinogens is likely an important
factor in its carcinogenicity. For the first time several types of
TS particulates (TSP) were compared in different primary cultured
human oral epithelial cells (NOE) for their abilities to affect metabolism
of the tobacco carcinogen, (BaP) to genotoxic products, and expression
of drug metabolizing enzymes. TSP from, reference filtered (2RF4),
mentholated (MS), reference unfiltered, (IR3), ultra low tar (UL),
and cigarettes that primarily heat tobacco (ECL) were tested. Cells
pretreated with TSP concentrations of 0.2–10 μg/ml generally
showed increased rates of BaP metabolism; those treated with TSP
concentrations above 10 μg/ml showed decreased rates. Effects
of TSPs were similar when expressed on a weight basis. Weights of
TSP/cigarette varied in the order: MS ≈ IR3 > 2RF4 > ECL > UL.
All TSPs induced the phase I proteins, cytochrome P450 1A1 (CYP1A1)
and 1B1 (CYP1B1), phase II proteins, NAD(P)H dehydrogenase quinone
1 (NQO1), and microsomal glutathione S-transferase 1 (MGST1), and
additionally, hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2),
as assessed by qRT-PCR. The pattern of gene induction at probable
physiological levels favored activation over detoxification.},
doi = {10.1016/j.fct.2011.06.037},
issn = {0278-6915},
keywords = {Tobacco},
url = {http://www.sciencedirect.com/science/article/pii/S027869151100281X}
}
@ARTICLE{Sackton2009,
author = {Sackton, Timothy B. and Kulathinal, Rob J. and Bergman, Casey M.
and Quinlan, Aaron R. and Dopman, Erik B. and Carneiro, Mauricio
and Marth, Gabor T. and Hartl, Daniel L. and Clark, Andrew G.},
title = {Population Genomic Inferences from Sparse High-Throughput Sequencing
of Two Populations of Drosophila melanogaster},
journal = {Genome Biol Evol},
year = {2009},
volume = {1},
pages = {449--465},
number = {0},
month = jan,
abstract = {Short-read sequencing techniques provide the opportunity to capture
genome-wide sequence data in a single experiment. A current challenge
is to identify questions that shallow-depth genomic data can address
successfully and to develop corresponding analytical methods that
are statistically sound. Here, we apply the Roche/454 platform to
survey natural variation in strains of Drosophila melanogaster from
an African (n = 3) and a North American (n = 6) population. Reads
were aligned to the reference D. melanogaster genomic assembly, single
nucleotide polymorphisms were identified, and nucleotide variation
was quantified genome wide. Simulations and empirical results suggest
that nucleotide diversity can be accurately estimated from sparse
data with as little as 0.2x coverage per line. The unbiased genomic
sampling provided by random short-read sequencing also allows insight
into distributions of transposable elements and copy number polymorphisms
found within populations and demonstrates that short-read sequencing
methods provide an efficient means to quantify variation in genome
organization and content. Continued development of methods for statistical
inference of shallow-depth genome-wide sequencing data will allow
such sparse, partial data sets to become the norm in the emerging
field of population genomics.},
url = {http://gbe.oxfordjournals.org/cgi/content/abstract/1/0/449}
}
@ARTICLE{Sadana2011,
author = {Sadana, Prabodh and Hwang, Jong Yeon and Attia, Ramy R. and Arnold,
Leggy A. and Neale, Geoffrey and Guy, R. Kiplin},
title = {Similarities and Differences between Two Modes of Antagonism of the
Thyroid Hormone Receptor},
journal = {ACS Chemical Biology},
year = {2011},
volume = {6},
pages = {1096-1106},
number = {10},
abstract = { Thyroid hormone (T3) mediates diverse physiological functions including
growth, differentiation, and energy homeostasis through the thyroid
hormone receptors (TR). The TR binds DNA at specific recognition
sequences in the promoter regions of their target genes known as
the thyroid hormone response elements (TREs). Gene expression at
TREs regulated by TRs is mediated by coregulator recruitment to the
DNA bound receptor. This TR–coregulator interaction controls transcription
of target genes by multiple mechanisms including covalent histone
modifications and chromatin remodeling. Our previous studies identified
a β-aminoketone as a potent inhibitor of the TR-coactivator interaction.
We describe here the activity of one of these inhibitors in modulating
effects of T3 signaling in comparison to an established ligand-competitive
inhibitor of TR, NH-3. The β-aminoketone was found to reverse thyroid
hormone induced gene expression by inhibiting coactivator recruitment
at target gene promoters, thereby regulating downstream effects of
thyroid hormone. While mimicking the downstream effects of NH-3 at
the molecular level, the β-aminoketone affects only a subset of
the thyroid responsive signaling network. Thus antagonists directed
to the coregulator binding site have distinct pharmacological properties
relative to ligand-based antagonists and may provide complementary
activity in vivo. },
doi = {10.1021/cb200092v},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/cb200092v},
url = {http://pubs.acs.org/doi/abs/10.1021/cb200092v}
}
@ARTICLE{Sadek2008,
author = {Sadek, Mikel and Hynecek, Robert L. and Goldenberg, Sagit and Kent,
K. Craig and Marin, Michael L. and Faries, Peter L.},
title = {Gene expression analysis of a porcine native abdominal aortic aneurysm
model},
journal = {Surgery},
year = {2008},
volume = {144},
pages = {252--258},
number = {2},
month = aug,
abstract = {Introduction We sought to characterize the gene expression patterns
occurring during the development of aneurysms in the native porcine
aorta.Methods In Yorkshire swine, the infrarenal aorta was balloon
dilated and infused with a solution of type I collagenase/pancreatic
porcine elastase (16,000 U/1,000 U). Aneurysmal and control aortic
samples were obtained at 1 (n = 3), 2 (n = 6), and 4 (n = 5) weeks
following aneurysm induction. RNA was isolated, converted to biotin-modified
antisense RNA and hybridized to porcine genome arrays. Aneurysmal
and control gene intensities were compared using the 2-sample-for-means
z-test. P < .01 was considered statistically significant.Results
Extracellular matrix remodeling genes that were upregulated in aneurysmal
compared with control tissue included matrix metalloproteinase-1,
-2, -3, and -9; MT-MMP; cathepsin-D, -H, -K, and -S; tissue inhibitor
of metalloproteinase-1; and collagen I-[alpha]1 chain (P < .01).
Elastin exhibited temporally downregulated gene expression (P < .01).
Inflammatory genes that were upregulated included intercellular adhesion
molecule-2, tumor necrosis factor-[alpha], interleukin (IL)-1[beta],
IL-10, chemokine receptor-4, and tissue plasminogen activator (P
< .01). Atherosclerosis and cancer genes that were upregulated included
apolipoprotein E, acyl-CoA binding protein, friend leukemia virus
integration-1, and E26 transformation-specific sequence (P < .01).Conclusion
The porcine model replicates the gene expression patterns that are
observed during the development of aneurysms in human studies as
well as in rodent models. The porcine model thereby represents a
novel method to study the impact of endovascular, cell-based, and
other therapeutic interventions on AAA pathophysiology.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4T25TDV-G/2/034d7f25132ff1f6e134923b2e32f41d}
}
@ARTICLE{Sadi2011,
author = {Sadi, Al Muktafi and Wang, Dong-Yu and Youngson, Bruce and Miller,
Naomi and Boerner, Scott and Done, Susan and Leong, Wey},
title = {Clinical relevance of DNA microarray analyses using archival formalin-fixed
paraffin-embedded breast cancer specimens},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {253},
number = {1},
abstract = {BACKGROUND:The ability of gene profiling to predict treatment response
and prognosis in breast cancers has been demonstrated in many studies
using DNA microarray analyses on RNA from fresh frozen tumor specimens.
In certain clinical and research situations, performing such analyses
on archival formalin fixed paraffin-embedded (FFPE) surgical specimens
would be advantageous as large libraries of such specimens with long-term
follow-up data are widely available. However, FFPE tissue processing
can cause fragmentation and chemical modifications of the RNA. A
number of recent technical advances have been reported to overcome
these issues. Our current study evaluates whether or not the technology
is ready for clinical applications.METHODS:A modified RNA extraction
method and a recent DNA microarray technique, cDNA-mediated annealing,
selection, extension and ligation (DASL, Illumina Inc) were evaluated.
The gene profiles generated from FFPE specimens were compared to
those obtained from paired fresh fine needle aspiration biopsies
(FNAB) of 25 breast cancers of different clinical subtypes (based
on ER and Her2/neu status). Selected RNA levels were validated using
RT-qPCR, and two public databases were used to demonstrate the prognostic
significance of the gene profiles generated from FFPE specimens.RESULTS:Compared
to FNAB, RNA isolated from FFPE samples was relatively more degraded,
nonetheless, over 80% of the RNA samples were deemed suitable for
subsequent DASL assay. Despite a higher noise level, a set of genes
from FFPE specimens correlated very well with the gene profiles obtained
from FNAB, and could differentiate breast cancer subtypes. Expression
levels of these genes were validated using RT-qPCR. Finally, for
the first time we correlated gene expression profiles from FFPE samples
to survival using two independent microarray databases. Specifically,
over-expression of ANLN and KIF2C, and under-expression of MAPT strongly
correlated with poor outcomes in breast cancer patients.CONCLUSION:We
demonstrated that FFPE specimens retained important prognostic information
that could be identified using a recent gene profiling technology.
Our study supports the use of FFPE specimens for the development
and refinement of prognostic gene signatures for breast cancer. Clinical
applications of such prognostic gene profiles await future large-scale
validation studies.},
doi = {10.1186/1471-2407-11-253},
issn = {1471-2407},
pubmedid = {21679412},
url = {http://www.biomedcentral.com/1471-2407/11/253}
}
@ARTICLE{SadighiAkha2011,
author = {Sadighi Akha, Amir A. and Harper, James M. and Salmon, Adam B. and
Schroeder, Bethany A. and Tyra, Heather M. and Rutkowski, D. Thomas
and Miller, Richard A.},
title = {Heightened Induction of Proapoptotic Signals in Response to Endoplasmic
Reticulum Stress in Primary Fibroblasts from a Mouse Model of Longevity},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {30344-30351},
number = {35},
abstract = {Previous work from our laboratory has shown that primary fibroblasts
from long-lived Snell dwarf mice display a higher sensitivity to
the lethal effects of endoplasmic reticulum (ER) stressors, such
as thapsigargin, than cells from normal mice. Here we show that thapsigargin
induces higher expression of CHOP, enhanced cleavage of caspase-12,
higher caspase-3 activity, and increased phosphorylation of c-JUN,
all indicators of enhanced apoptosis, in dwarf fibroblasts. Dwarf
and normal fibroblasts show no genotypic difference in up-regulating
BiP, GRP94, and ERp72 proteins after exposure to thapsigargin. However,
dwarf fibroblasts express lower basal levels of a number of putative
XBP1 target genes including Armet, Edem1, Erdj3, p58IPK and Sec61a1,
as well as Ire1 itself. Furthermore, when exposed to thapsigargin,
dwarf fibroblasts display attenuated splicing of Xbp1, but similar
phosphorylation of eIF2, in comparison to normal fibroblasts. These
data support the notion that IRE1/XBP1 signaling is set at a lower
level in dwarf fibroblasts. Diminished Xbp1 splicing in dwarf-derived
fibroblasts may tilt the balance between prosurvival and proapoptotic
signals in favor of apoptosis, thereby leading to higher induction
of proapoptotic signals in these cells and ultimately their increased
sensitivity to ER stressors. These results, together with recent
findings in Caenorhabditis elegans daf-2 mutants, point to a potential
interplay between insulin/IGF-1 signals and unfolded protein response
signaling.},
doi = {10.1074/jbc.M111.220541},
eprint = {http://www.jbc.org/cgi/reprint/286/35/30344.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/35/30344}
}
@ARTICLE{Sadikovic2010,
author = {Sadikovic, Bekim and Thorner, Paul and Chilton-MacNeill, Susan and
Martin, Jeff and Cervigne, Nilva and Squire, Jeremy and Zielenska,
Maria},
title = {Expression analysis of genes associated with human osteosarcoma tumors
shows correlation of RUNX2 overexpression with poor response to chemotherapy},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {202},
number = {1},
abstract = {BACKGROUND:Human osteosarcoma is the most common pediatric bone tumor.
There is limited understanding of the molecular mechanisms underlying
osteosarcoma oncogenesis, and a lack of good diagnostic as well as
prognostic clinical markers for this disease. Recent discoveries
have highlighted a potential role of a number of genes including:
RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B,
BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.METHODS:Our objective was to
assess relative expression levels of these 16 genes as potential
biomarkers of osteosarcoma oncogenesis and chemotherapy response
in human tumors. We performed quantitative expression analysis in
a panel of 22 human osteosarcoma tumors with differential response
to chemotherapy, and 5 normal human osteoblasts.RESULTS:RECQL4, SPP1,
RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A,
RB1, P53, and LSAMP showed significant loss of expression relative
to normal osteoblasts. In addition to being overexpressed in osteosarcoma
tumor samples relative to normal osteoblasts, RUNX2 was the only
gene of the 16 to show significant overexpression in tumors that
had a poor response to chemotherapy relative to good responders.CONCLUSION:These
data underscore the loss of tumor suppressive pathways and activation
of specific oncogenic mechanisms associated with osteosarcoma oncogenesis,
while drawing attention to the role of RUNX2 expression as a potential
biomarker of chemotherapy failure in osteosarcoma.},
doi = {10.1186/1471-2407-10-202},
issn = {1471-2407},
pubmedid = {20465837},
url = {http://www.biomedcentral.com/1471-2407/10/202}
}
@ARTICLE{Sadlon2010,
author = {Sadlon, Timothy J. and Wilkinson, Bridget G. and Pederson, Stephen
and Brown, Cheryl Y. and Bresatz, Suzanne and Gargett, Tessa and
Melville, Elizabeth L. and Peng, Kaimen and D'Andrea, Richard J.
and Glonek, Gary G. and Goodall, Gregory J. and Zola, Heddy and Shannon,
M. Frances and Barry, Simon C.},
title = {Genome-Wide Identification of Human FOXP3 Target Genes in Natural
Regulatory T Cells},
journal = {J. Immunol.},
year = {2010},
volume = {185},
pages = {1071--1081},
number = {2},
month = jul,
abstract = {The transcription factor FOXP3 is essential for the formation and
function of regulatory T cells (Tregs), and Tregs are essential for
maintaining immune homeostasis and tolerance. This is demonstrated
by a lethal autoimmune defect in mice lacking Foxp3 and in immunodysregulation
polyendocrinopathy enteropathy X-linked syndrome patients. However,
little is known about the molecular basis of human FOXP3 function
or the relationship between direct and indirect targets of FOXP3
in human Tregs. To investigate this, we have performed a comprehensive
genome-wide analysis for human FOXP3 target genes from cord blood
Tregs using chromatin immunoprecipitation array profiling and expression
profiling. We have identified 5579 human FOXP3 target genes and derived
a core Treg gene signature conserved across species using mouse chromatin
immunoprecipitation data sets. A total of 739 of the 5579 FOXP3 target
genes were differentially regulated in Tregs compared with Th cells,
thus allowing the identification of a number of pathways and biological
functions overrepresented in Tregs. We have identified gene families
including cell surface molecules and microRNAs that are differentially
expressed in FOXP3+ Tregs. In particular, we have identified a novel
role for peptidase inhibitor 16, which is expressed on the cell surface
of >80% of resting human CD25+FOXP3+ Tregs, suggesting that in conjunction
with CD25 peptidase inhibitor 16 may be a surrogate surface marker
for Tregs with potential clinical application.},
url = {http://www.jimmunol.org/cgi/content/abstract/185/2/1071}
}
@ARTICLE{Sadovsky2006,
author = {Sadovsky, Yoel and Wyatt, Solange M. and Collins, Lynne and Elchalal,
Uriel and Kraus, Fredrick T. and Nelson, D. Michael},
title = {The use of needle biopsy for assessment of placental gene expression},
journal = {American Journal of Obstetrics and Gynecology},
year = {2006},
volume = {194},
pages = {1137--1142},
number = {4},
month = apr,
abstract = {Objective The purpose of this study was to test the hypothesis that
placental samples that are obtained by needle aspiration ex vivo
are useful for the determination of villus gene expression.Study
design Placental biopsy was performed with a spinal needle after
uncomplicated deliveries. Villi were inspected microscopically, and
RNA was extracted and analyzed with capillary electrophoresis. Gene
expression was determined with quantitative polymerase chain reaction.Results
We obtained more placental villous fragments per aspiration using
a 20-gauge needle (5.2 ± 1.8 fragments) than with a 22-gauge needle
(3.3 ± 1.6 fragments; P < .01). RNA quality was adequate, based on
the 28S and 18S recombinant RNA bands, with a mean 260/280 ratio
of 1.88. The amount of extracted RNA correlated with the number of
villous fragments per aspirate. Importantly, the expression of NDRG1
and hPL, both markedly altered in hypoxia, was consistent between
villi that were obtained by either needle or standard biopsy.Conclusion
Placental samples that are obtained by ex vivo needle aspiration
are useful for the extraction of RNA and for the determination of
villous gene expression.},
issn = {0002-9378},
keywords = {Placenta, Villus, Needle aspiration, RNA, Quantitative polymerase
chain reaction},
url = {http://www.sciencedirect.com/science/article/B6W9P-4JKRFTC-1K/2/c7bb4b45808630b460f6c2c04fca24cb}
}
@ARTICLE{Saeki2009,
author = {Saeki, Yuko and Endo, Takaho and Ide, Kaori and Nagashima, Takeshi
and Yumoto, Noriko and Toyoda, Tetsuro and Suzuki, Harukazu and Hayashizaki,
Yoshihide and Sakaki, Yoshiyuki and Okada-Hatakeyama, Mariko},
title = {Ligand-specific sequential regulation of transcription factors for
differentiation of MCF-7 cells},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {545},
number = {1},
abstract = {BACKGROUND:Sharing a common ErbB/HER receptor signaling pathway, heregulin
(HRG) induces differentiation of MCF-7 human breast cancer cells
while epidermal growth factor (EGF) elicits proliferation. Although
cell fates resulting from action of the aforementioned ligands completely
different, the respective gene expression profiles in early transcription
are qualitatively similar, suggesting that gene expression during
late transcription, but not early transcription, may reflect ligand
specificity. In this study, based on both the data from time-course
quantitative real-time PCR on over 2,000 human transcription factors
and microarray of all human genes, we identified a series of transcription
factors which may control HRG-specific late transcription in MCF-7
cells.RESULTS:We predicted that four transcription factors including
EGR4, FRA-1, FHL2, and DIPA should have responsibility of regulation
in MCF-7 cell differentiation. Validation analysis suggested that
one member of the activator protein 1 (AP-1) family, FOSL-1 (FRA-1
gene), appeared immediately following c-FOS expression, might be
responsible for expression of transcription factor FHL2 through activation
of the AP-1 complex. Furthermore, RNAi gene silencing of FOSL-1 and
FHL2 resulted in increase of extracellular signal-regulated kinase
(ERK) phosphorylation of which duration was sustained by HRG stimulation.CONCLUSION:Our
analysis indicated that a time-dependent transcriptional regulatory
network including c-FOS, FRA-1, and FHL2 is vital in controlling
the ERK signaling pathway through a negative feedback loop for MCF-7
cell differentiation.},
doi = {10.1186/1471-2164-10-545},
issn = {1471-2164},
pubmedid = {19925682},
url = {http://www.biomedcentral.com/1471-2164/10/545}
}
@ARTICLE{SAFAIYAN2011,
author = {SAFAIYAN, S. and BOLHASSANI, A. and NYLEN, S. and AKUFFO, H. and
RAFATI, S.},
title = {Contribution of human neutrophils in the development of protective
immune response during in vitro Leishmania major infection},
journal = {Parasite Immunology},
year = {2011},
volume = {33},
pages = {609--620},
number = {11},
abstract = {Stimulation of neutrophils may potentiate immunity to Leishmania major.
CpG-containing oligodeoxynucleotide (ODN) has immune stimulatory
effects and has been suggested as adjuvants and therapeutics to potentiate
efficacy of vaccines and treatments against leishmaniasis. Here,
we examined the stimulatory effect of synthetic ODN containing CpG
motifs class A and B on cytokine production by neutrophils. Neutrophils
from healthy donors responded to CpG-ODN type A, but not to class
B, with secretion of IL-8 and following GM-CSF pretreatment with
TNF-α production. To test whether neutrophil responses were altered
in cutaneous leishmaniasis (CL) and to better understand the role
of neutrophils in susceptibility and resistance to disease, we evaluated
cytokine responses in GM-CSF preconditioned neutrophils from asymptomatic
(Leishmanin skin test positive, LST+) and nonhealing CL individuals
to CpG-ODN class A and assessed the expression levels of toll-like
receptors (TLR2), 4 and 9. LST+ and healthy donor, but not nonhealing
CL neutrophils, responded with TNF-α secretion. Neutrophils from
nonhealing CL displayed increased mRNA expression levels of TLR2,
4 and 9 compared to neutrophils from LST+ or healthy donors. Therefore,
failure to cure CL is associated with reduced ability of neutrophils
to secrete TNF-α and correlates with high TLR 2, 4 and 9 expressions.},
doi = {10.1111/j.1365-3024.2011.01321.x},
issn = {1365-3024},
keywords = {cytokines, inflammation, Leishmania major, leishmaniasis, neutrophils,
ODN, TLR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3024.2011.01321.x}
}
@ARTICLE{Safdar2011a,
author = {Safdar, Adeel and Bourgeois, Jacqueline M. and Ogborn, Daniel I.
and Little, Jonathan P. and Hettinga, Bart P. and Akhtar, Mahmood
and Thompson, James E. and Melov, Simon and Mocellin, Nicholas J.
and Kujoth, Gregory C. and Prolla, Tomas A. and Tarnopolsky, Mark
A.},
title = {Endurance exercise rescues progeroid aging and induces systemic mitochondrial
rejuvenation in mtDNA mutator mice},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {4135-4140},
number = {10},
abstract = {A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian
aging is supported by recent studies demonstrating that the mtDNA
mutator mouse, harboring a defect in the proofreading-exonuclease
activity of mitochondrial polymerase gamma, exhibits accelerated
aging phenotypes characteristic of human aging, systemic mitochondrial
dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic
studies in humans have demonstrated that endurance training reduces
the risk of chronic diseases and extends life expectancy. Whether
endurance exercise can attenuate the cumulative systemic decline
observed in aging remains elusive. Here we show that 5 mo of endurance
exercise induced systemic mitochondrial biogenesis, prevented mtDNA
depletion and mutations, increased mitochondrial oxidative capacity
and respiratory chain assembly, restored mitochondrial morphology,
and blunted pathological levels of apoptosis in multiple tissues
of mtDNA mutator mice. These adaptations conferred complete phenotypic
protection, reduced multisystem pathology, and prevented premature
mortality in these mice. The systemic mitochondrial rejuvenation
through endurance exercise promises to be an effective therapeutic
approach to mitigating mitochondrial dysfunction in aging and related
comorbidities.},
doi = {10.1073/pnas.1019581108},
eprint = {http://www.pnas.org/cgi/reprint/108/10/4135.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/10/4135}
}
@ARTICLE{Safdar2011,
author = {Safdar, Adeel and Little, Jonathan P. and Stokl, Andrew J. and Hettinga,
Bart P. and Akhtar, Mahmood and Tarnopolsky, Mark A.},
title = {Exercise Increases Mitochondrial PGC-1{alpha} Content and Promotes
Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {10605--10617},
number = {12},
month = mar,
abstract = {Endurance exercise is known to induce metabolic adaptations in skeletal
muscle via activation of the transcriptional co-activator peroxisome
proliferator-activated receptor {gamma} co-activator 1 (PGC-1). PGC-1
regulates mitochondrial biogenesis via regulating transcription of
nuclear-encoded mitochondrial genes. Recently, PGC-1 has been shown
to reside in mitochondria; however, the physiological consequences
of mitochondrial PGC-1 remain unknown. We sought to delineate if
an acute bout of endurance exercise can mediate an increase in mitochondrial
PGC-1 content where it may co-activate mitochondrial transcription
factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group;
[female] = [male]) were randomly assigned to sedentary (SED), forced-endurance
(END) exercise (15 m/min for 90 min), or forced endurance +3 h of
recovery (END+3h) group. The END group was sacrificed immediately
after exercise, whereas the SED and END+3h groups were euthanized
3 h after acute exercise. Acute exercise coordinately increased the
mRNA expression of nuclear and mitochondrial DNA-encoded mitochondrial
transcripts. Nuclear and mitochondrial abundance of PGC-1 in END
and END+3h groups was significantly higher versus SED mice. In mitochondria,
PGC-1 is in a complex with mitochondrial transcription factor A at
mtDNA D-loop, and this interaction was positively modulated by exercise,
similar to the increased binding of PGC-1 at the NRF-1 promoter.
We conclude that in response to acute altered energy demands, PGC-1
re-localizes into nuclear and mitochondrial compartments where it
functions as a transcriptional co-activator for both nuclear and
mitochondrial DNA transcription factors. These results suggest that
PGC-1 may dynamically facilitate nuclear-mitochondrial DNA cross-talk
to promote net mitochondrial biogenesis.},
comment = {10.1074/jbc.M110.211466},
url = {http://www.jbc.org/cgi/content/abstract/286/12/10605}
}
@ARTICLE{Safdar2008,
author = {Safdar, Adeel and Yardley, Nicholas J. and Snow, Rodney and Melov,
Simon and Tarnopolsky, Mark A.},
title = {Global and targeted gene expression and protein content in skeletal
muscle of young men following short-term creatine monohydrate supplementation},
journal = {Physiol Genomics},
year = {2008},
volume = {32},
pages = {219--228},
number = {2},
month = jan,
abstract = {Creatine monohydrate (CrM) supplementation has been shown to increase
fat-free mass and muscle power output possibly via cell swelling.
Little is known about the cellular response to CrM. We investigated
the effect of short-term CrM supplementation on global and targeted
mRNA expression and protein content in human skeletal muscle. In
a randomized, placebo-controlled, crossover, double-blind design,
12 young, healthy, nonobese men were supplemented with either a placebo
(PL) or CrM (loading phase, 20 g/day x 3 days; maintenance phase,
5 g/day x 7 days) for 10 days. Following a 28-day washout period,
subjects were put on the alternate supplementation for 10 days. Muscle
biopsies of the vastus lateralis were obtained and were assessed
for mRNA expression (cDNA microarrays + real-time PCR) and protein
content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation
significantly increased fat-free mass, total body water, and body
weight of the participants (P < 0.05). Also, CrM supplementation
significantly upregulated (1.3- to 5.0-fold) the mRNA content of
genes and protein content of kinases involved in osmosensing and
signal transduction, cytoskeleton remodeling, protein and glycogen
synthesis regulation, satellite cell proliferation and differentiation,
DNA replication and repair, RNA transcription control, and cell survival.
We are the first to report this large-scale gene expression in the
skeletal muscle with short-term CrM supplementation, a response that
suggests changes in cellular osmolarity.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/32/2/219}
}
@ARTICLE{Sagan2010,
author = {Sagan, Selena M. and Nasheri, Neda and Luebbert, Christian and Pezacki,
John Paul},
title = {The Efficacy of siRNAs against Hepatitis C Virus Is Strongly Influenced
by Structure and Target Site Accessibility},
journal = {Chemistry \& Biology},
year = {2010},
volume = {17},
pages = {515--527},
number = {5},
month = may,
abstract = {Summary Hepatitis C virus (HCV) is a global health problem. Designing
therapeutic agents that target HCV's RNA genome remains challenging.
HCV genomic RNA is large and highly structured with long-range genome-scale
ordered RNA structures. Predicting the secondary- and tertiary-structure
elements that reveal the accessibility of target sites within HCV
RNA is difficult because of the abundance of long-range interactions.
Target site accessibility remains a significant barrier to the design
of effective therapeutics such as small interfering RNAs (siRNAs)
against different strains of HCV. Here we developed two methods that
interrogate the folding of HCV RNA, an approach involving viral RNA
microarrays (VRMs) and an HCV viral RNA-coated magnetic bead-based
(VRB) assay. VRMs and VRBs were used to determine target site accessibility
for siRNAs designed against the HCV genome. Both methods predicted
potency of siRNAs in cell-culture models for HCV replication that
are not easily predicted by informatic means.},
issn = {1074-5521},
keywords = {CHEMBIO, MICROBIO, HUMDISEASE},
url = {http://www.sciencedirect.com/science/article/B6VRP-505NKTB-G/2/afbdae4640ecb6ae0add99b992cc0982}
}
@ARTICLE{Saghir2008,
author = {Saghir, Shakil A. and Charles, Grantley D. and Bartels, Michael J.
and Kan, Lynn H.L. and Dryzga, Mark D. and Brzak, Kathy A. and Clark,
Amy J.},
title = {Mechanism of trifluralin-induced thyroid tumors in rats},
journal = {Toxicology Letters},
year = {2008},
volume = {180},
pages = {38--45},
number = {1},
month = jul,
abstract = {Trifluralin, an herbicide, has been reported to cause a significant
increase in thyroid follicular cell tumors in male Fischer 344 rats.
This study was designed to determine the mechanism of thyroid hyperactivity
after trifluralin exposure. A group of 15 male Fischer 344 rats were
exposed to trifluralin-fortified (6500 ppm) diet for 2 weeks. The
time weighted average daily intake of trifluralin was 441 ± 77 mg/kg/day.
Ten rats of the group were sacrificed and the sera analyzed for T3,
T4, and TSH levels. The livers were also analyzed for selected T4-specific
UGT gene expression and total UGT enzyme activity. In the trifluralin
treated rats, the serum T3 and T4 levels decreased by 17% and 90%,
respectively and TSH increased by 37% more than the control rats.
Trifluralin-induced total hepatic UGT enzymes (2.4-fold) and mRNA
expression of selected hepatic UGT isozymes (UGT1A1, 1.4-fold; UGT1A6,
6.4-fold; UGT2B1, 3.7-fold). For the remaining 5 rats in the group,
bile was collected for 2 h and analyzed for free and conjugated T3
and T4. The total amount of T4 in bile more than doubled in trifluralin
treated rats. Trifluralin treatment increased bile flow, caused a
3.2-fold increase in biliary elimination of conjugated T4 and 63%
increase in conjugated T3. Based on these data, the decrease in total
serum T3 and T4 levels in the trifluralin treated rats was due to
enhanced peripheral metabolism and an increase in bile flow that
results in a compensatory increase in TSH synthesis and secretion.
The increased levels of TSH with chronic exposure to trifluralin
would exert a continuous stimulation of the thyroid gland leading
to cellular hypertrophy and proliferation predisposing to the development
of follicular cell tumors in rats.},
issn = {0378-4274},
keywords = {Trifluralin, Dinitroanilines, Thyroxine (T4), Triiodothyronine (T3),
Thyroid stimulating hormone (TSH), Thyroid tumor in rats},
url = {http://www.sciencedirect.com/science/article/B6TCR-4SP3SPG-1/2/4cd0a2a91ccf4a5242b64a30b91088d3}
}
@ARTICLE{Saghizadeh2009,
author = {Saghizadeh, Mehrnoosh and Akhmedov, Novrouz B. and Yamashita, Clyde
K. and Gribanova, Yekaterina and Theendakara, Veena and Mendoza,
Emmanuel and Nelson, Stanley F. and Ljubimov, Alexander V. and Farber,
Debora B.},
title = {ZBED4, a BED-Type Zinc-Finger Protein in the Cones of the Human Retina},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {3580--3588},
number = {8},
month = aug,
abstract = {PURPOSE. To characterize the ZBED4 cDNA identified by subtractive
hybridization and microarray of retinal cone degeneration (cd) adult
dog mRNA from mRNA of normal dog retina. METHODS. The cDNA library
obtained from subtractive hybridization was arrayed and screened
with labeled amplicons from normal and cd dog retinas. Northern blot
analysis was used to verify ZBED4 mRNA expression in human retina.
Flow cytometry sorted peanut agglutinin (PNA)-labeled cones from
dissociated mouse retinas, and quantitative RT-PCR (QPCR) was used
to measure ZBED4 mRNA levels in these cone cells. Immunohistochemistry
localized ZBED4 in human retinas. Expression of ZBED4 mRNA transiently
transfected into HEK293 cells was analyzed by immunofluorescence.
ZBED4 subcellular localization was determined with Western blot analysis.
RESULTS. One of 80 cDNAs differentially expressed in normal and cd
dog retinas corresponded to a novel gene, ZBED4, which is also expressed
in human and mouse retinas. ZBED4 mRNA was found to be present in
cone photoreceptors. When ZBED4 cDNA was transfected into HEK293
cells, the expressed protein showed nuclear localization. However,
in human retinas, ZBED4 was localized to cone nuclei, inner segments,
and pedicles, as well as to Muller cell endfeet. Confirming these
immunohistochemical results, the 135-kDa ZBED4 was found in both
the nuclear and cytosolic extracts of human retinas. ZBED4 has four
predicted DNA-binding domains, a dimerization domain, and two LXXLL
motifs characteristic of coactivators/corepressors of nuclear hormone
receptors. CONCLUSIONS. ZBED4 cellular/subcellular localization and
domains suggest a regulatory role for this protein, which may exert
its effects in cones and Muller cells through multiple ways of action.},
url = {http://www.iovs.org/cgi/content/abstract/50/8/3580}
}
@ARTICLE{Saghizadeh2005,
author = {Saghizadeh, Mehrnoosh and Kramerov, Andrei A. and Tajbakhsh, Jian
and Aoki, Annette M. and Wang, Charles and Chai, Ning-Ning and Ljubimova,
Julia Y. and Sasaki, Takako and Sosne, Gabriel and Carlson, Marc
R. J. and Nelson, Stanley F. and Ljubimov, Alexander V.},
title = {Proteinase and Growth Factor Alterations Revealed by Gene Microarray
Analysis of Human Diabetic Corneas},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2005},
volume = {46},
pages = {3604--3615},
number = {10},
month = oct,
abstract = {PURPOSE. To identify proteinases and growth factors abnormally expressed
in human corneas of donors with diabetic retinopathy (DR), additional
to previously described matrix metalloproteinase (MMP)-10 and -3
and insulin-like growth factor (IGF)-I. METHODS. RNA was isolated
from 35 normal, diabetic, and DR autopsy human corneas ex vivo or
after organ culture. Amplified cRNA was analyzed using 22,000-gene
microarrays (Agilent Technologies, Palo Alto, CA). Gene expression
in each diabetic corneal cRNA was assessed against pooled cRNA from
7 to 9 normal corneas. Select differentially expressed genes were
validated by quantitative real-time RT-PCR (QPCR) and immunohistochemistry.
Organ cultures were treated with a cathepsin inhibitor, cystatin
C, or MMP-10. RESULTS. More than 100 genes were upregulated and 2200
were downregulated in DR corneas. Expression of cathepsin F and hepatocyte
growth factor (HGF) genes was increased in ex vivo and organ-cultured
DR corneas compared with normal corneas. HGF receptor c-met, fibroblast
growth factor (FGF)-3, its receptor FGFR3, tissue inhibitor of metalloproteinase
(TIMP)-4, laminin {alpha}4 chain, and thymosin {beta}4 genes were
downregulated. The data were corroborated by QPCR and immunohistochemistry
analyses; main changes of these components occurred in corneal epithelium.
In organ-cultured DR corneas, cystatin C increased laminin-10 and
integrin {alpha}3{beta}1, whereas in normal corneas MMP-10 decreased
laminin-10 and integrin {alpha}3{beta}1 expression. CONCLUSIONS.
Elevated cathepsin F and the ability of its inhibitor to produce
a more normal phenotype in diabetic corneas suggest increased proteolysis
in these corneas. Proteinase changes may result from abnormalities
of growth factors, such as HGF and FGF-3, in DR corneas. Specific
modulation of proteinases and growth factors could reduce diabetic
corneal epitheliopathy.},
url = {http://www.iovs.org/cgi/content/abstract/46/10/3604}
}
@ARTICLE{Sagirkaya2007,
author = {Sagirkaya, Hakan and Misirlioglu, Muge and Kaya, Abdullah and First,
Neal L. and Parrish, John J. and Memili, Erdogan},
title = {Developmental potential of bovine oocytes cultured in different maturation
and culture conditions},
journal = {Animal Reproduction Science},
year = {2007},
volume = {101},
pages = {225--240},
number = {3-4},
month = oct,
abstract = {Diverse groups of chemicals in culture media are needed for successful
bovine oocyte maturation and embryo development during which dramatic
cytoplasmic and nuclear reprogramming events take place. In vitro
embryo production (IVP) procedures frequently include supplements
such as serum and/or co-culture with various types of somatic cells.
However, the presence of undefined serum in culture media introduces
a variation from batch to batch, increases viral or prion contamination
risk, and leads to problems during fetal development. The aim of
the present study was to investigate the possibility of using chemically
defined-synthetic serum substitute (SSS) in place of fetal calf serum
(FCS) during maturation and long-term culture to stimulate in vitro
maturation (IVM), fertilization (IVF) and subsequent embryo development.
In Experiment I, the effect of the protein source on in vitro maturation
was tested by maturing oocytes in culture media supplemented with
10% FCS (Control Group), 10% SSS (Group I) and 10% SSS + 10 ng/ml
epidermal growth factor (EGF) (Group II). In Experiment II, effects
of SSS on both oocyte maturation and embryo development during in
vitro culture (IVC) were tested by maturing oocytes in media supplemented
with 10% FCS (FCS Group) or 10% SSS + 10 ng/ml EGF (SSS Group), followed
by IVF and IVC in SOF media supplemented with 10% FCS and 10% SSS
on day 4 for FCS and SSS Groups, respectively. Even though rates
for cleavage and development to blastocyst stage were not different,
blastocyst cell numbers were higher in Group II containing SSS and
EGF. The SSS supplementation group had higher apoptotic nuclei as
compared to the FCS Group in Experiment II. Transcripts for heat
shock protein 70 (Hsp70), interferon tau (IF-[tau]), DNA methyltransferase
3a (Dnmt3a), desmosomal glycoprotein desmocollin III (DcIII) and
insulin-like growth factor II receptor (Igf-2r) were altered in different
culture conditions in Experiment I. However, only glucose transporter-1
(Glut-1) mRNA was different in the SSS and FCS Groups in the second
experiment. In summary, SSS and EGF in maturation medium and replacement
of FCS with SSS alone in culture medium on day 4 of IVC support oocyte
maturation and embryo development in vitro. However, significance
of culture condition induced changes on the genome-wide abundance
of messenger ribonucleic acid and the significance of the apoptotic
nuclei during fetal development still remain to be determined.},
issn = {0378-4320},
keywords = {Early development, Gametogenesis, Oocyte development, Embryo, Developmental
biology},
url = {http://www.sciencedirect.com/science/article/B6T43-4M4TNPR-1/2/3c9ac0b360770ca3ea35532ca6cd8965}
}
@ARTICLE{Sagirkaya2006,
author = {Sagirkaya, Hakan and Misirlioglu, Muge and Kaya, Abdullah and First,
Neal L and Parrish, John J and Memili, Erdogan},
title = {Developmental and molecular correlates of bovine preimplantation
embryos},
journal = {Reproduction},
year = {2006},
volume = {131},
pages = {895--904},
number = {5},
month = may,
abstract = {Expression of embryonic genes is altered in different culture conditions,
which influence developmental potential both during preimplantation
and fetal development. The objective of this study was to define
the effects of culture conditions on: bovine embryonic development
to blastocyst stage, blastocyst cell number, apoptosis and expression
patterns of a panel of developmentally important genes. Bovine embryos
were cultured in vitro in three culture media containing amino acids,
namely potassium simplex optimization medium (KSOMaa), Charles Rosenkrans
1 (CR1aa) and synthetic oviductal fluid (SOFaa). Apoptosis in blastocysts
was determined by TUNEL assay and expression profiles of developmentally
important genes were assayed by real-time PCR. In vivo-produced bovine
blastocysts were used as controls for experiments determining gene
expression patterns. While the cleavage rates did not differ, embryos
cultured in SOFaa had higher rates of development to blastocyst stage
(P < 0.05). Mean cell numbers and percentages of apoptotic cells
per blastocyst did not differ among the groups. Expression of the
heat shock protein 70 (Hsp70) gene was significantly up-regulated
in both CR1aa and KSOMaa when compared with SOFaa (P < 0.001). DNA
methyltransferase 3a (Dnmt3a) expression was higher in embryos cultured
in CR1aa than in those cultured in SOFaa (P < 0.001). Expression
of interferon tau (IF-{tau}) and insulin-like growth factor II receptor
(Igf-2r) genes was significantly up-regulated in KSOMaa when compared
with CR1aa (P < 0.001). Gene expression did not differ between in
vivo-derived blastocysts and their in vitro-derived counterparts.
In conclusion, SOFaa supports higher development to blastocyst stage
than KSOMaa and CR1aa, and the culture conditions influence gene
expression.},
url = {http://www.reproduction-online.org/cgi/content/abstract/131/5/895}
}
@ARTICLE{Sagiv2008,
author = {Sagiv, Eyal and Starr, Alex and Rozovski, Uri and Khosravi, Rami
and Altevogt, Peter and Wang, Timothy and Arber, Nadir},
title = {Targeting CD24 for Treatment of Colorectal and Pancreatic Cancer
by Monoclonal Antibodies or Small Interfering RNA},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {2803--2812},
number = {8},
month = apr,
abstract = {CD24 is a potential oncogene reported to be overexpressed in a large
variety of human malignancies. We have shown that CD24 is overexpressed
in 90% of colorectal tumors at a fairly early stage in the multistep
process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb)
induce a significant growth inhibition in colorectal and pancreatic
cancer cell lines that express the protein. This study is designed
to investigate further the effects of CD24 down-regulation using
mAb or small interfering RNA in vitro and in vivo. Western blot analysis
showed that anti-CD24 mAb induced CD24 protein down-regulation through
lysosomal degradation. mAb augmented growth inhibition in combination
with five classic chemotherapies. Xenograft models in vivo showed
that tumor growth was significantly reduced in mAb-treated mice.
Similarly, stable growth inhibition of cancer cell lines was achieved
by down-regulation of CD24 expression using short hairpin RNA (shRNA).
The produced clones proliferated more slowly, reached lower saturation
densities, and showed impaired motility. Most importantly, down-regulation
of CD24 retarded tumorigenicity of human cancer cell lines in nude
mice. Microarray analysis revealed a similar pattern of gene expression
alterations when cells were subjected to anti-CD24 mAb or shRNA.
Genes in the Ras pathway, mitogen-activated protein kinase, or BCL-2
family and others of oncogenic association were frequently down-regulated.
As a putative new oncogene that is overexpressed in gastrointestinal
malignancies early in the carcinogenesis process, CD24 is a potential
target for early intervention in the prevention and treatment of
cancer. [Cancer Res 2008;68(8):2803-12]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/8/2803}
}
@ARTICLE{Sagstad2007,
author = {Sagstad, A and Sanden, M and Haugland, Ø and Hansen, A-C and Olsvik,
P A and Hemre, G-I},
title = {Evaluation of stress- and immune-response biomarkers in Atlantic
salmon, Salmo salar L., fed different levels of genetically modified
maize (Bt maize), compared with its near-isogenic parental line and
a commercial suprex maize},
journal = {Journal of Fish Diseases},
year = {2007},
volume = {30},
pages = {201--212},
number = {4},
abstract = {Abstract The present study was designed to evaluate if genetically
modified (GM) maize (Bt maize, event MON810) compared with the near-isogenic
non-modified (nGM) maize variety, added as a starch source at low
or high inclusions, affected fish health of post-smolt Atlantic salmon,
Salmo salar L. To evaluate the health impact, selected stress- and
immune-response biomarkers were quantified at the gene transcript
(mRNA) level, and some also at the protein level. The diets with
low or high inclusions of GM maize, and its near-isogenic nGM parental
line, were compared to a control diet containing GM-free suprex maize
(reference diet) as the only starch source. Total superoxide dismutase
(SOD) activity in liver and distal intestine was significantly higher
in fish fed GM maize compared with fish fed nGM maize and with the
reference diet group. Fish fed GM maize showed significantly lower
catalase (CAT) activity in liver compared with fish fed nGM maize
and to the reference diet group. In contrast, CAT activity in distal
intestine was significantly higher for fish fed GM maize compared
with fish fed reference diet. Protein level of heat shock protein
70 (HSP70) in liver was significantly higher in fish fed GM maize
compared with fish fed the reference diet. No diet-related differences
were found in normalized gene expression of SOD, CAT or HSP70 in
liver or distal intestine. Normalized gene expression of interleukin-1
beta in spleen and head-kidney did not vary significantly between
diet groups. Interestingly, fish fed high GM maize showed a significantly
larger proportion of plasma granulocytes, a significantly larger
sum of plasma granulocyte and monocyte proportions, but a significantly
smaller proportion of plasma lymphocytes, compared with fish fed
high nGM maize. In conclusion, Atlantic salmon fed GM maize showed
some small changes in stress protein levels and activities, but none
of these changes were comparable to the normalized gene expression
levels analysed for these stress proteins. GM maize seemed to induce
significant changes in white blood cell populations which are associated
with an immune response.},
issn = {1365-2761},
keywords = {antioxidant enzymes, Atlantic salmon, Bt maize, gene expression, genetically
modified, stress proteins},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2761.2007.00808.x}
}
@ARTICLE{Sagstad2008,
author = {Sagstad, A. And Sanden, M. And Krogdahl, Ã…. And Bakke-mckellep,
A.m. And Frã˜ystad, M. And Hemre, G.-i.},
title = {Organs development, gene expression and health of Atlantic salmon
(Salmo salar L.) fed genetically modified soybeans compared to the
near-isogenic non-modified parental line},
journal = {Aquaculture Nutrition},
year = {2008},
volume = {14},
pages = {556--572},
number = {6},
abstract = {Abstract The present experiment was conducted to study the possible
effects of genetically modified (GM), full-fat soybean meal (FFSBM)
from Round-up Ready® soybeans compared to its parental, and closest
near-isogenic, non-modified (nGM) soybean variety, added at moderate
(150 g kg−1) and high (300 g kg−1) inclusion levels. The
fish showed a high specific growth rate (SGR 1.27–1.52), and nearly
doubled their body weight (BW), with final weights varying from 1009
to 1110Â g. Increased levels of dietary FFSBM, independent of the
soy being GM or not, significantly decreased mean values of SGR,
thermal growth rate, condition factor, final BW, liver somatic index,
lipid efficiency ratio, apparent digestibility coefficients (ADC)
of protein and gross energy, liver lipid content and plasma cholesterol,
and significantly increased ADC of starch and muscle fatty acid levels
of 18:3n-3, 20:4n-6, 20:5n-3 and total n-3. Increasing dietary GM
FFSBM significantly increased feed conversion ratio, and significantly
decreased protein efficiency ratio, ADC of lipid and dry matter and
plasma triacylglycerol (TAG) levels. Spleen somatic index was significantly
larger in fish groups fed GM FFSBM compared to groups fed nGM FFSBM,
which might indicate a possible immune response exerted by the GM
soybeans. Mean normalized expression of heat shock protein 70 mRNA
in distal intestine was significantly up-regulated while normalized
expression of catalase in liver was down-regulated, in fish fed FFSBM
compared to fish fed FM. In conclusion, substituting moderate to
high levels of GM Round-up Ready® FFSBM in diets for Atlantic salmon
and compared to the closest near-isogenic counterpart available,
resulted in many effects independent of the soy being GM or not,
but with the notable exceptions of enlarged spleen and lowered plasma
TAG.},
issn = {1365-2095},
keywords = {Atlantic salmon, gene expression, genetically modified, growth, health,
soybean, stress proteins},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2095.2008.00630.x}
}
@ARTICLE{Saheki2007,
author = {Saheki, Takeyori and Iijima, Mikio and Li, Meng Xian and Kobayashi,
Keiko and Horiuchi, Masahisa and Ushikai, Miharu and Okumura, Fumihiko
and Meng, Xiao Jian and Inoue, Ituro and Tajima, Atsushi and Moriyama,
Mitsuaki and Eto, Kazuhiro and Kadowaki, Takashi and Sinasac, David
S. and Tsui, Lap-Chee and Tsuji, Mihoko and Okano, Akira and Kobayashi,
Tsuyoshi},
title = {Citrin/Mitochondrial Glycerol-3-phosphate Dehydrogenase Double Knock-out
Mice Recapitulate Features of Human Citrin Deficiency},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {25041--25052},
number = {34},
month = aug,
abstract = {Citrin is the liver-type mitochondrial aspartate-glutamate carrier
that participates in urea, protein, and nucleotide biosynthetic pathways
by supplying aspartate from mitochondria to the cytosol.Citrin also
plays a role in transporting cytosolic NADH reducing equivalents
into mitochondria as a component of the malate-aspartate shuttle.
In humans, loss-of-function mutations in the SLC25A13 gene encoding
citrin cause both adult-onset type II citrullinemia and neonatal
intrahepatic cholestasis, collectively referred to as human citrin
deficiency. Citrin knock-out mice fail to display features of human
citrin deficiency. Based on the hypothesis that an enhanced glycerol
phosphate shuttle activity may be compensating for the loss of citrin
function in the mouse, we have generated mice with a combined disruption
of the genes for citrin and mitochondrial glycerol 3-phosphate dehydrogenase.
The resulting double knock-out mice demonstrated citrullinemia, hyperammonemia
that was further elevated by oral sucrose administration, hypoglycemia,
and a fatty liver, all features of human citrin deficiency. An increased
hepatic lactate/pyruvate ratio in the double knock-out mice compared
with controls was also further elevated by the oral sucrose administration,
suggesting that an altered cytosolic NADH/NAD+ ratio is closely associated
with the hyperammonemia observed. Microarray analyses identified
over 100 genes that were differentially expressed in the double knock-out
mice compared with wild-type controls, revealing genes potentially
involved in compensatory or downstream effects of the combined mutations.
Together, our data indicate that the more severe phenotype present
in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double
knock-out mice represents a more accurate model of human citrin deficiency
than citrin knock-out mice.},
url = {http://www.jbc.org/cgi/content/abstract/282/34/25041}
}
@ARTICLE{Saher2009,
author = {Saher, Gesine and Quintes, Susanne and Mobius, Wiebke and Wehr, Michael
C. and Kramer-Albers, Eva-Maria and Brugger, Britta and Nave, Klaus-Armin},
title = {Cholesterol Regulates the Endoplasmic Reticulum Exit of the Major
Membrane Protein P0 Required for Peripheral Myelin Compaction},
journal = {J. Neurosci.},
year = {2009},
volume = {29},
pages = {6094--6104},
number = {19},
month = may,
abstract = {Rapid impulse conduction requires electrical insulation of axons by
myelin, a cholesterol-rich extension of the glial cell membrane with
a characteristic composition of proteins and lipids. Mutations in
several myelin protein genes cause endoplasmic reticulum (ER) retention
and disease, presumably attributable to failure of misfolded proteins
to pass the ER quality control. Because many myelin proteins partition
into cholesterol-rich membrane rafts, their interaction with cholesterol
could potentially be part of the ER quality control system. Here,
we provide in vitro and in vivo evidence that the major peripheral
myelin protein P0 requires cholesterol for exiting the ER and reaching
the myelin compartment. Cholesterol dependency of P0 trafficking
in heterologous cells is mediated by a cholesterol recognition/interaction
amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol
biosynthesis in Schwann cells suffer from severe hypomyelination
with numerous uncompacted myelin stretches. This demonstrates that
high-level cholesterol coordinates P0 export with myelin membrane
synthesis, which is required for the correct stoichiometry of myelin
components and for myelin compaction.},
url = {http://www.jneurosci.org/cgi/content/abstract/29/19/6094}
}
@ARTICLE{Sahu2011,
author = {Sahu, Gautam and Cloyd, Miles},
title = {Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase
inhibitors},
journal = {Virology Journal},
year = {2011},
volume = {8},
pages = {400},
number = {1},
abstract = {Recently, there is considerable interest in the field of anti-HIV
therapy to identify and develop chromatin-modifying histone deacetylase
(HDAC) inhibitors that can effectively reactivate latent HIV in patients.
The hope is that this would help eliminate cells harboring latent
HIV and achieve an eventual cure of the virus. However, how effectively
these drugs can stimulate latent HIVs in quiescent primary CD4 T
cells, despite their relevant potencies demonstrated in cell line
models of HIV latency, is not clear. Here, we show that the HDAC
inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable
to reactivate HIV in latently infected primary CD4 T cells generated
in the H80 co-culture system. This raises a concern that the drugs
inhibiting HDAC function alone might not be sufficient for stimulating
latent HIV in resting CD4 T cells in patients and not achieve any
anticipated reduction in the pool of latent reservoirs.},
doi = {10.1186/1743-422X-8-400},
issn = {1743-422X},
pubmedid = {21838863},
url = {http://www.virologyj.com/content/8/1/400}
}
@ARTICLE{Said2006,
author = {Said, Mahmoud M. and Hokaiwado, Naomi and Tang, Mingxi and Ogawa,
Kumiko and Suzuki, Shugo and Ghanem, Hala M. and Esmat, Amr Y. and
Asamoto, Makoto and Refaie, Fawzia M. and Shirai, Tomoyuki},
title = {Inhibition of prostate carcinogenesis in probasin/SV40 T antigen
transgenic rats by leuprorelin, a luteinizing hormone–releasing
hormone agonist},
journal = {Cancer Science},
year = {2006},
volume = {97},
pages = {459--467},
number = {6},
abstract = {The effects of leuprorelin acetate, a luteinizing hormone-releasing
hormone agonist (LHRH-A), on prostate carcinogenesis in probasin/SV40
Tag transgenic rat was investigated. Fifteen weeks after administration
of 0.28 and 2.8Â mg/kg leuprorelin, prostate weights and serum testosterone
levels were significantly decreased compared to values for transgenic
controls. Histopathological findings revealed that the incidence
of prostatic adenocarcinomas was significantly reduced in ventral,
dorsal and lateral lobes of the prostate, correlating with decreased
expression of SV40 Tag oncoprotein as well as inhibition of DNA synthesis
and proliferation of epithelial cells in neoplastic lesions of the
ventral prostate. Microarray analysis further showed leuprorelin
acetate to significantly inhibit testicular steroidogenesis, suppressing
the expression of SV40 Tag oncoprotein and altering the expression
of a large number of genes which might be involved in the inhibition
of prostate cancer progression in this rat model. (Cancer Sci 2006;
97: 459–467)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2006.00213.x}
}
@ARTICLE{Saidi2009,
author = {Saidi, Ahlame and Hagedorn, Martin and Allain, Nathalie and Verpelli,
Chiara and Sala, Carlo and Bello, Lorenzo and Bikfalvi, Andreas and
Javerzat, Sophie},
title = {Combined targeting of interleukin-6 and vascular endothelial growth
factor potently inhibits glioma growth and invasiveness},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {1054--1064},
number = {5},
abstract = {Abstract 10.1002/ijc.24380.abs Interleukin-6 (IL6) and vascular endothelial
growth factor (VEGFA) are abundantly produced by glioma cells and
contribute to malignancy by promoting angiogenesis, cell proliferation
and resistance to apoptosis. We compared the effect of inhibiting
IL6 and VEGF on U87-derived experimental glioma grown on the chick
chorio-allantoic membrane (CAM) or in the brain of xenografted mice.
Tumor growth was monitored by biomicroscopy and immunohistology.
In vitro, IL6 knockdown had no effect on proliferation but substantially
enhanced invasion. In the CAM experimental glioma, IL6 or VEGF knockdown
reduced growth and vascularization of the tumors with a comparable
efficiency, but increased invasion of residual tumor cells. In contrast,
combined IL6/VEGF knockdown not only showed enhanced reduction of
tumor growth and angiogenesis but also significantly prevented invasion
of residual tumor cells. In mice, combining IL6 knockdown and Avastinâ„¢
treatment completely abrogated tumor development and infiltration.
Molecular response of tumor cells to single or combined treatment
was studied by transcriptomic profiling. Many cell cycle promoting
genes and chromatin components were silenced in the double knockdown.
In addition, specific migratory signatures detected in tumors under
single IL6 or VEGF knockdown were partially erased in combined IL6/VEGF
knockdown tumors. Our results show that treatment with a combination
of IL6 and VEGF inhibitors brings synergistic antitumoral benefit
and reduces global activity of major pathways of cell survival, proliferation
and invasiveness in remaining tumor cells that may be induced by
using VEGF or IL6 inhibitors alone. © 2009 UICC},
issn = {1097-0215},
keywords = {glioblastoma, anti-angiogenesis, invasion, combinatory therapy, vascular
endothelial growth factor, interleukin 6, microarray},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24380}
}
@ARTICLE{Saidi2008,
author = {Saidi, Ahlame and Javerzat, Sophie and Bellahcène, Akeila and De
Vos, John and Bello, Lorenzo and Castronovo, Vincent and Deprez,
Manuel and Loiseau, Hugues and Bikfalvi, Andreas and Hagedorn, Martin},
title = {Experimental anti-angiogenesis causes upregulation of genes associated
with poor survival in glioblastoma},
journal = {Int. J. Cancer},
year = {2008},
volume = {122},
pages = {2187--2198},
number = {10},
abstract = {Abstract Vascular endothelial growth factor (VEGF) inhibitors are
the most promising anti-angiogenic agents used increasingly in the
clinic. However, to be efficient, anti-VEGF agents need to be associated
with classic chemotherapy. Exploring gene regulation in tumor cells
during anti-angiogenesis might help to comprehend the molecular basis
of response to treatment. To generate a defined anti-angiogenic condition
in vivo, we transfected human glioma cells with short-interfering
RNAs against VEGF-A and implanted them on the chick chorio-allantoic
membrane. Gene regulation in avascular tumors was studied using human
Affymetrixâ„¢ GeneChips. Potentially important genes were further
studied in glioma patients. Despite strong VEGF inhibition, we observed
recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin
and CHI3L1, which encodes for YKL-40, a putative prognosticator for
various diseases, including cancer, were strongly up-regulated in
avascular glioma. In glioblastoma patients, these genes showed coregulation
and their expression differed significantly from low-grade glioma.
Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA
(p = 0.0004) were significantly correlated with poor survival. Cox
regression analysis further confirmed that PI3 and CHI3L1 levels
are survival markers independent from patient age and sex. Elafin-positive
tumor cells were only found in glioblastoma, where they were clustered
around necrotic areas. PI3/elafin is strongly induced by serum deprivation
and hypoxia in U87 glioma cells in vitro. Our results indicate that
anti-angiogenesis in experimental glioma drives expression of critical
genes which relate to disease aggressiveness in glioblastoma patients.
In particular, CHI3L1 and PI3/elafin may be useful as new prognostic
markers and new therapeutic targets. © 2007 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {anti-angiogenesis, glioblastoma, microarray, elafin, YKL-40},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23313}
}
@ARTICLE{Saint-Mezard2009,
author = {Saint-Mezard, Pierre and Berthier, Céline C. and Zhang, Hai and
Hertig, Alexandre and Kaiser, Sergio and Schumacher, Martin and Wieczorek,
Grazyna and Bigaud, Marc and Kehren, Jeanne and Rondeau, Eric and
Raulf, Friedrich and Marti, Hans-Peter},
title = {Analysis of independent microarray datasets of renal biopsies identifies
a robust transcript signature of acute allograft rejection},
journal = {Transplant International},
year = {2009},
volume = {22},
pages = {293--302},
number = {3},
abstract = {Summary Transcriptomics could contribute significantly to the early
and specific diagnosis of rejection episodes by defining ‘molecular
Banff’ signatures. Recently, the description of pathogenesis-based
transcript sets offered a new opportunity for objective and quantitative
diagnosis. Generating high-quality transcript panels is thus critical
to define high-performance diagnostic classifier. In this study,
a comparative analysis was performed across four different microarray
datasets of heterogeneous sample collections from two published clinical
datasets and two own datasets including biopsies for clinical indication,
and samples from nonhuman primates. We characterized a common transcriptional
profile of 70 genes, defined as acute rejection transcript set (ARTS).
ARTS expression is significantly up-regulated in all AR samples as
compared with stable allografts or healthy kidneys, and strongly
correlates with the severity of Banff AR types. Similarly, ARTS were
tested as a classifier in a large collection of 143 independent biopsies
recently published by the University of Alberta. Results demonstrate
that the ‘in silico’ approach applied in this study is able to
identify a robust and reliable molecular signature for AR, supporting
a specific and sensitive molecular diagnostic approach for renal
transplant monitoring.},
issn = {1432-2277},
keywords = {acute rejection, biopsies for clinical indication, comparative analysis,
gene expression, kidney, molecular diagnostic, transplantation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1432-2277.2008.00790.x}
}
@ARTICLE{Saintenac2011,
author = {Saintenac, Cyrille and Jiang, Dayou and Akhunov, Eduard},
title = {Targeted analysis of nucleotide and copy number variation by exon
capture in allotetraploid wheat genome},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R88},
number = {9},
abstract = {BACKGROUND:The ability of grass species to adapt to various habitats
is attributed to the dynamic nature of their genomes, which have
been shaped by multiple rounds of ancient and recent polyploidization.
To gain a better understanding of the nature and extent of variation
in functionally relevant regions of a polyploid genome, we developed
a sequence capture assay to compare exonic sequences of allotetraploid
wheat accessions.RESULTS:A sequence capture assay was designed for
the targeted re-sequencing of 3.5 Mb exon regions that surveyed a
total of 3,497 genes from allotetraploid wheat. These data were used
to describe SNPs, copy number variation and homoeologous sequence
divergence in coding regions. A procedure for variant discovery in
the polyploid genome was developed and experimentally validated.
About 1% and 24% of discovered SNPs were loss-of-function and non-synonymous
mutations, respectively. Under-representation of replacement mutations
was identified in several groups of genes involved in translation
and metabolism. Gene duplications were predominant in a cultivated
wheat accession, while more gene deletions than duplications were
identified in wild wheat.CONCLUSIONS:We demonstrate that, even though
the level of sequence similarity between targeted polyploid genomes
and capture baits can bias enrichment efficiency, exon capture is
a powerful approach for variant discovery in polyploids. Our results
suggest that allopolyploid wheat can accumulate new variation in
coding regions at a high rate. This process has the potential to
broaden functional diversity and generate new phenotypic variation
that eventually can play a critical role in the origin of new adaptations
and important agronomic traits.},
doi = {10.1186/gb-2011-12-9-r88},
issn = {1465-6906},
pubmedid = {21917144},
url = {http://genomebiology.com/2011/12/9/R88}
}
@ARTICLE{Saito2006,
author = {Saito, Kiyomi and Arata, Satoru and Hosono, Tomohiko and Sano, Yoshihiro
and Takahashi, Katsuhiko and Choi-Miura, Nam-Ho and Nakano, Yasuko
and Tobe, Takashi and Tomita, Motowo},
title = {Adiponectin plays an important role in efficient energy usage under
energy shortage},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology
of Lipids},
year = {2006},
volume = {1761},
pages = {709--716},
number = {7},
month = jul,
abstract = {Adiponectin is an adipose tissue-specific secretory protein known
to be an insulin-sensitizing protein. In this study, we generated
adiponectin sense and antisense transgenic (Tg) mice to investigate
whether adiponectin plays a role in the regulation of energy homeostasis
during the growth stage. Spontaneous motor activity of antisense
Tg mice were markedly reduced during fasting, particularly in young
female mice, compared with wild type (Wt) and sense Tg mice. Furthermore,
both body weight and adipose tissue mass of the antisense female
Tg mice drastically reduced during fasting. To examine the relationship
between the collapse of abdominal white adipose tissue (WAT) and
serum adiponectin level, we measured the expression of genes related
to energy expenditure, such as uncoupling protein (UCP). Notably,
the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly
less than that of Wt mice and the UCP1 mRNA was strongly increased
during fasting. These findings suggest that the serum adiponectin
is important to maintaining energy homeostasis under energy shortage
conditions, such as over female pubertal development.},
issn = {1388-1981},
keywords = {Adiponectin, Adipose tissue, Fasting, UCP},
url = {http://www.sciencedirect.com/science/article/B6VNN-4K19NRY-1/2/2d7a13f97f37beae16fe874477c58e9a}
}
@ARTICLE{Saito2011a,
author = {Saito, Motonobu and Schetter, Aaron J. and Mollerup, Steen and Kohno,
Takashi and Skaug, Vidar and Bowman, Elise D. and Mathe, Ewy A. and
Takenoshita, Seiichi and Yokota, Jun and Haugen, Aage and Harris,
Curtis C.},
title = {The Association of MicroRNA Expression with Prognosis and Progression
in Early-Stage, Non-Small Cell Lung Adenocarcinoma: A Retrospective
Analysis of Three Cohorts},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {1875--1882},
number = {7},
month = apr,
abstract = {Purpose: There is increasing evidence that altered microRNA expression
is associated with tumor progression and survival in cancer patients.
We tested if the expression of specific microRNAs was associated
with prognosis and disease progression in early-stage lung adenocarcinoma.
Experimental Design: The expression of miR-21, miR-17, and miR-155
was measured by quantitative RT-PCR in tissues from 317 non-small
cell lung cancer (NSCLC) patients that originated from Maryland,
Norway, and Japan. Kaplan-Meier and Cox regression analysis evaluated
associations of microRNA expression with cancer-specific mortality
and disease-free survival. Results: Elevated miR-21 (HR 2.06, 1.13-3.75),
miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was
associated with worse cancer-specific mortality in the Maryland cohort.
These were evaluated in two additional cohorts and only miR-21 was
associated with worse cancer-specific mortality in the Norwegian
cohort (HR 2.78, 1.22-6.31) and worse relapse-free survival in the
Japanese cohort (HR 2.82, 1.57-5.07). More advanced stage tumors
expressed significantly higher levels of miR-21 compared with TNM
stage I tumors. TNM stage I patients were evaluated separately and
high levels of miR-21 was associated with worse cancer-specific mortality
(HR 2.16, 1.11-4.21) and relapse-free survival (3.40, 1.57-7.36)
independent of other clinical factors. Conclusions: This is the first
study to report that increased miR-21 expression is associated with
disease progression and survival in stage I lung cancer. This suggests
that expression of miR-21 may contribute to lung carcinogenesis and
serve as a therapeutic target or early-stage prognostic biomarker
for lung adenocarcinoma. Clin Cancer Res; 17(7); 1875-82. (C)2011
AACR.},
comment = {10.1158/1078-0432.CCR-10-2961},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/7/1875}
}
@ARTICLE{Saito2011b,
author = {Rumiko Saito and Satoshi Hirakawa and Hiroshi Ohara and Makoto Yasuda
and Tomomi Yamazaki and Shigeaki Nishii and Setsuya Aiba},
title = {Nickel differentially regulates NFAT and NF-κB activation in T cell
signaling},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {254},
pages = {245 - 255},
number = {3},
abstract = {Nickel is a potent hapten that induces contact hypersensitivity in
human skin. While nickel induces the maturation of dendritic cells
via NF-κB and p38 MAPK activation, it also exerts immunosuppressive
effects on T cells through an unknown mechanism. To elucidate the
molecular mechanisms of its effects on T cells, we examined the effects
of NiCl2 on mRNA expression in human CD3+ T cells stimulated with
CD3 and CD28 antibodies. Using a DNA microarray and Gene Ontology,
we identified 70 up-regulated (including IL-1β, IL-6 and IL-8) and
61 down-regulated (including IL-2, IL-4, IL-10 and IFN-γ) immune
responsive genes in NiCl2-treated T cells. The DNA microarray results
were verified using real-time PCR and a Bio-PlexTM suspension protein
array. Suppression of IL-2 and IFN-γ gene transcription by NiCl2
was also confirmed using Jurkat T cells transfected with IL-2 or
IFN-γ luciferase reporter genes. To explore the NiCl2-regulated
signaling pathway, we examined the binding activity of nuclear proteins
to NFAT, AP-1, and NF-κB consensus sequences. NiCl2 significantly
and dose-dependently suppressed NFAT- and AP-1-binding activity,
but augmented NF-κB-binding activity. Moreover, NiCl2 decreased
nuclear NFAT expression in stimulated T cells. Using Jurkat T cells
stimulated with PMA/ionomycin, we demonstrated that NiCl2 significantly
suppressed stimulation-evoked cytosolic Ca2+ increases, suggesting
that NiCl2 regulates NFAT signals by acting as a blocker of Ca2+
release-activated Ca2+ (CRAC) channels. These data showed that NiCl2
decreases NFAT and increases NF-κB signaling in T cells. These results
shed light on the effects of nickel on the molecular regulation of
T cell signaling.},
doi = {10.1016/j.taap.2011.04.017},
issn = {0041-008X},
keywords = {nickel},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11001669}
}
@ARTICLE{Saito2011d,
author = {Saito, Rumiko and Hirakawa, Satoshi and Ohara, Hiroshi and Yasuda,
Makoto and Yamazaki, Tomomi and Nishii, Shigeaki and Aiba, Setsuya},
title = {Nickel differentially regulates NFAT and NF-[kappa]B activation in
T cell signaling},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {254, 3},
pages = {245–255},
abstract = {Nickel is a potent hapten that induces contact hypersensitivity in
human skin. While nickel induces the maturation of dendritic cells
via NF-[kappa]B and p38 MAPK activation, it also exerts immunosuppressive
effects on T cells through an unknown mechanism. To elucidate the
molecular mechanisms of its effects on T cells, we examined the effects
of NiCl2 on mRNA expression in human CD3+ T cells stimulated with
CD3 and CD28 antibodies. Using a DNA microarray and Gene Ontology,
we identified 70 up-regulated (including IL-1[beta], IL-6 and IL-8)
and 61 down-regulated (including IL-2, IL-4, IL-10 and IFN-[gamma])
immune responsive genes in NiCl2-treated T cells. The DNA microarray
results were verified using real-time PCR and a Bio-PlexTM suspension
protein array. Suppression of IL-2 and IFN-[gamma] gene transcription
by NiCl2 was also confirmed using Jurkat T cells transfected with
IL-2 or IFN-[gamma] luciferase reporter genes. To explore the NiCl2-regulated
signaling pathway, we examined the binding activity of nuclear proteins
to NFAT, AP-1, and NF-[kappa]B consensus sequences. NiCl2 significantly
and dose-dependently suppressed NFAT- and AP-1-binding activity,
but augmented NF-[kappa]B-binding activity. Moreover, NiCl2 decreased
nuclear NFAT expression in stimulated T cells. Using Jurkat T cells
stimulated with PMA/ionomycin, we demonstrated that NiCl2 significantly
suppressed stimulation-evoked cytosolic Ca2+ increases, suggesting
that NiCl2 regulates NFAT signals by acting as a blocker of Ca2+
release-activated Ca2+ (CRAC) channels. These data showed that NiCl2
decreases NFAT and increases NF-[kappa]B signaling in T cells. These
results shed light on the effects of nickel on the molecular regulation
of T cell signaling.},
issn = {0041-008X},
keywords = {nickel, NFAT, AP-1, NF-[kappa]B, CRAC},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11001669}
}
@ARTICLE{Saito2008,
author = {Saito, Shigeru and Ojima, Hidenori and Ichikawa, Hitoshi and Hirohashi,
Setsuo and Kondo, Tadashi},
title = {Molecular background of α-fetoprotein in liver cancer cells as revealed
by global RNA expression analysis},
journal = {Cancer Science},
year = {2008},
volume = {99},
pages = {2402--2409},
number = {12},
abstract = {α-Fetoprotein (AFP) is considered to be a diagnostic and prognostic
biomarker in hepatocellular carcinoma (HCC). However, the role of
AFP in the development of HCC is presently obscure. We hypothesized
that a certain set of genes is expressed in a manner coordinate with
AFP, and that these genes essentially contribute to the malignant
characteristics of AFP-producing HCC. To address this hypothesis,
we carried out global mRNA expression analysis of 21 liver cancer
cell lines that produce varying levels of AFP. We identified 213
genes whose mRNA expression levels were significantly correlated
with that of AFP (PÂ <Â 0.0001). These included liver-specific transcription
factors for AFP and other albumin family genes. Eighteen HCC-associated
genes and 11 genes associated with malignancies other than HCC showed
significant correlations with AFP production levels. Genes involved
in lipid catabolism, blood coagulation, iron metabolism, angiogenesis,
and the Wnt and mitogen-activated protein kinase pathways were also
identified. Text data mining revealed that participation in the transcription
factor network could explain the connection between 78 of the identified
genes. Glypican 3, which is a component of the Wnt pathway and contributes
to HCC development, had the fifth highest correlation coefficient
with AFP. Reactivity to specific antibodies confirmed the significant
correlation between AFP and glypican 3 expression in HCC tissues.
These observations suggest that AFP-producing liver cancer cells
may have a unique molecular background consisting of cancer-associated
genes. From this genome-wide association study, novel aspects of
the molecular background of AFP were revealed, and thus may lead
to the identification of novel biomarker candidates. (Cancer Sci
2008; 99: 2402–2409)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2008.00973.x}
}
@ARTICLE{Saito2011,
author = {Saito, Sakae and Tomida, Akihiro},
title = {Use of Chemical Genomics in Assessment of the UPR},
journal = {Methods in Enzymology},
year = {2011},
volume = {Volume 491},
pages = {327--341},
abstract = {Glucose deprivation, one of the major physiological conditions in
solid tumor, leads to activation of the unfolded protein response
(UPR) in cancer cells. The UPR occurs through the transcriptional
and translational regulatory mechanisms that improve the capacity
of the endoplasmic reticulum (ER) to fold and traffic proteins and
allows the cell to survive under stress conditions. We previously
reported that the macrocyclic compound versipelostatin and the antidiabetic
biguanides metformin, buformin, and phenformin could inhibit the
UPR during glucose deprivation as well as induce the UPR by treatment
of cells with 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Versipelostatin
and biguanides show highly selective cytotoxicity to glucose-deprived
tumor cells and exert in vivo antitumor activity; thus, these compounds
would be interesting anticancer agent candidates. By microarray analysis,
we demonstrated that cancer cells under glucose deprivation conditions
caused activation of the UPR transcription program, which was suppressed
broadly by versipelostatin and biguanides. We also identified the
drug-driven gene signatures that can be used to discover pharmacologic
UPR modulators. Indeed, we found several bioactive drugs, such as
pyrvinium pamoate, valinomycin, and rottlerin, that selectively suppressed
2DG-induced GRP78 promoter activity as versipelostatin and biguanide
did. Together with growing bioinformatics databases and analytical
tools, our approach could provide a chemical genomic basis for developing
UPR-targeting drugs against solid tumors.},
booktitle = {The Unfolded Protein Response and Cellular Stress, Part C},
editor = {Conn, P. Michael},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/pii/B9780123859280000183}
}
@BOOK{Saito2011c,
title = {Chapter eighteen - Use of Chemical Genomics in Assessment of the
UPR},
publisher = {Academic Press},
year = {2011},
editor = {P. Michael Conn},
author = {Sakae Saito and Akihiro Tomida},
volume = {491},
pages = {327 - 341},
series = {Methods in Enzymology},
abstract = {Abstract Glucose deprivation, one of the major physiological conditions
in solid tumor, leads to activation of the unfolded protein response
(UPR) in cancer cells. The UPR occurs through the transcriptional
and translational regulatory mechanisms that improve the capacity
of the endoplasmic reticulum (ER) to fold and traffic proteins and
allows the cell to survive under stress conditions. We previously
reported that the macrocyclic compound versipelostatin and the antidiabetic
biguanides metformin, buformin, and phenformin could inhibit the
UPR during glucose deprivation as well as induce the UPR by treatment
of cells with 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Versipelostatin
and biguanides show highly selective cytotoxicity to glucose-deprived
tumor cells and exert in vivo antitumor activity; thus, these compounds
would be interesting anticancer agent candidates. By microarray analysis,
we demonstrated that cancer cells under glucose deprivation conditions
caused activation of the UPR transcription program, which was suppressed
broadly by versipelostatin and biguanides. We also identified the
drug-driven gene signatures that can be used to discover pharmacologic
UPR modulators. Indeed, we found several bioactive drugs, such as
pyrvinium pamoate, valinomycin, and rottlerin, that selectively suppressed
2DG-induced GRP78 promoter activity as versipelostatin and biguanide
did. Together with growing bioinformatics databases and analytical
tools, our approach could provide a chemical genomic basis for developing
UPR-targeting drugs against solid tumors.},
booktitle = {The Unfolded Protein Response and Cellular Stress, Part C},
doi = {10.1016/B978-0-12-385928-0.00018-3},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/pii/B9780123859280000183}
}
@ARTICLE{Sajduda2006,
author = {Sajduda, Anna and Dziadek, Jaroslaw and Kotlowski, Roman and Portaels,
Françoise},
title = {Evaluation of multiple genetic markers for typing drug-resistant
Mycobacterium tuberculosis strains from Poland},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2006},
volume = {55},
pages = {59--64},
number = {1},
month = may,
abstract = {In the present study, 77 drug-resistant Mycobacterium tuberculosis
strains isolated in Poland in 2000 were characterized by the mycobacterial
interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR)
typing and our novel method based on PCR amplification of DNA regions
between IS6110 and 16-bp GC-rich frequent repeats (designated IS6110-Mtb1/Mtb2
PCR). The results were compared with previous data of the more commonly
used methods, IS6110 restriction fragment length polymorphism (RFLP)
and spoligotyping. The discriminatory power of IS6110-Mtb1/Mtb2 method
was only slightly lower than that of IS6110 RFLP, whereas MIRU-VNTR
typing was the least discriminative among the 4 methods used. Clustering
of strains by using results of IS6110-Mtb1/Mtb2 PCR correlated well
with RFLP-defined clusters, further confirming epidemiologic relationships
among patients. These results indicate that the novel genotyping
method could be an attractive alternative for other PCR-based typing
procedures, such as spoligotyping and MIRU-VNTR typing. Also, it
seems to be a valuable adjunct to the reference IS6110 RFLP method
for studying the genetic diversity of drug-resistant M. tuberculosis
strains in Poland.},
issn = {0732-8893},
keywords = {Genetic markers, Genotyping, Drug resistance, Mycobacterium tuberculosis,
Poland},
url = {http://www.sciencedirect.com/science/article/B6T60-4J9N0SN-6/2/d82616f60f22e0531b4276a607f00585}
}
@ARTICLE{Sajduda2012,
author = {Anna Sajduda and Anandi Martin and Françoise Portaels and Juan Carlos
Palomino},
title = {hsp65 PCR-restriction analysis (PRA) with capillary electrophoresis
for species identification and differentiation of Mycobacterium kansasii
and Mycobacterium chelonae–Mycobacterium abscessus group},
journal = {International Journal of Infectious Diseases},
year = {2012},
pages = { - },
number = {0},
abstract = {SummaryObjectives The aim of the present study was to identify and
differentiate Mycobacterium kansasii and Mycobacterium chelonae–Mycobacterium
abscessus group strains isolated from clinical and environmental
sources in different countries. Methods PCR-restriction analysis
of the hsp65 gene (PRA) with automated capillary electrophoresis
was applied to the isolates previously identified by conventional
biochemical testing and the molecular INNO-LiPA MYCOBACTERIA assay.
Results PRA performed very well in comparison with the two other
methods (96.4% concordance). Among 27 M. kansasii isolates,
this method detected five genetic types, of which type 1 represented
the most common clinical isolate, as it is worldwide. PRA differentiated
29 M. chelonae–M. abscessus group isolates into Mycobacterium
immunogenum type 2 (n = 13), M. chelonae (n = 12),
and M. abscessus types 1 (n = 1) and 2 (n = 1).
M. immunogenum was the most frequent (69%) isolate from humans, but
only one of 11 cases was clinically significant. M. chelonae was
the most commonly (83%) recovered from water. PRA also identified
two isolates with hsp65 alleles representing previously unreported
patterns. Conclusions PRA based on automated capillary electrophoresis
is a rapid, simple, and reliable method for the identification and
differentiation of both clinically relevant and environmental isolates
of M. kansasii and M. chelonae–M. abscessus group.},
doi = {10.1016/j.ijid.2011.11.011},
issn = {1201-9712},
keywords = {Mycobacterium kansasii},
url = {http://www.sciencedirect.com/science/article/pii/S1201971211002487}
}
@ARTICLE{Sajduda2010,
author = {Sajduda, Anna and Martin, Anandi and Portaels, Françoise and Palomino,
Juan Carlos},
title = {hsp65 PCR-restriction analysis (PRA) with capillary electrophoresis
in comparison to three other methods for identification of Mycobacterium
species},
journal = {Journal of Microbiological Methods},
year = {2010},
volume = {80},
pages = {190--197},
number = {2},
month = feb,
abstract = {We developed a scheme for rapid identification of Mycobacterium species
using an automated fluorescence capillary electrophoresis instrument.
A 441-bp region of the hsp65 gene was examined using PCR-restriction
analysis (PRA). The assay was initially evaluated on 38 reference
strains. The observed sizes of restriction fragments were consistently
smaller than the real sizes for each of the species as deduced from
the sequence analysis (mean variance = 7 bp). Nevertheless, the obtained
PRA patterns were highly reproducible and resulted in correct species
identifications. A blind test was then successfully performed on
64 test isolates previously characterized by conventional biochemical
methods, a commercial INNO-LiPA Mycobacteria assay and/or sequence
determination of the 5' end of 16 S rRNA gene. A total of 14 of 64
isolates were erroneously identified by conventional methods (78%
accuracy). In contrast, PRA performed very well in comparison with
the LiPA (89% concordance) and especially with DNA sequencing (93.3%
of concordant results). Also, PRA identified seven isolates representing
five previously unreported hsp65 alleles. We conclude that hsp65
PRA based on automated capillary electrophoresis is a rapid, simple
and reliable method for identification of mycobacteria.},
issn = {0167-7012},
keywords = {Capillary electrophoresis, hsp65, Non-tuberculous mycobacteria, PRA,
Species identification},
url = {http://www.sciencedirect.com/science/article/B6T30-4Y34PTB-2/2/33f57a9843e684f820e8e82448dcdb31}
}
@ARTICLE{Sakai2005,
author = {Sakai, Kazuko and Arao, Tokuzo and Shimoyama, Tatsu and Murofushi,
Kimiko and Sekijima, Masaru and Kaji, Naoko and Tamura, Tomohide
and Saijo, Nagahiro and Nishio, Kazuto},
title = {Dimerization and the signal transduction pathway of a small in-frame
deletion in the epidermal growth factor receptor},
journal = {FASEB J},
year = {2005},
volume = {20},
pages = {311-313},
month = dec,
abstract = {A short, in-frame deletional mutant (E746-A750del) is one of the major
mutant forms of epidermal growth factor receptor (EGFR) and has been
reported to be a determinant of response to EGFR tyrosine kinase
inhibitors such as gefitinib and erlotinib. However, the biological
and pharmacological functions of mutational EGFR remain unclear.
To clarify these biological functions of deletional EGFR, we examined
the cellular response to EGF ligand stimulation. Dimerization and
phosphorylation of EGFR were observed without any ligand stimulation
in the 293(D) cells transfected with deletional EGFR as compared
with those transfected with wild-type EGFR (293(W) cells). When the
293(D) cells were exposed to gefitinib, an immunoblotting analysis
revealed remarkable inhibition of AKT phosphorylation but not phospho-p44/42
MAPK. To examine the cellular response in a lung cancer cell line
intrinsically expressing deletional EGFR, phospho-EGFR, and downstream
reactions were monitored under EGF stimulation with a beads-based
mulitiplex assay. EGFR and its downstream proteins were constitutively
phosphorylated in the PC-9 cells without any ligand stimulation as
compared with A549 lung cancer cells expressing wild-type EGFR. In
conclusion, deletional EGFR is constitutively active and phosphorylates
p44/42 MAPK and AKT in the cells, although the fact that the EGFR
phosphorylation in the PC-9 cells is still modulated by EGF stimulation
cannot be ignored. Gefitinib-inhibited phospho-AKT predominantly
in deletional EGFR expressing cells. Key words: mutation gefitinib
tyrosine kinase},
url = {http://www.fasebj.org/cgi/content/abstract/05-4034fjev1}
}
@ARTICLE{Sakai2009,
author = {Sakai, Yoshihisa and Goodison, Steve and Kusmartsev, Sergei and Fletcher,
Bradley and Eruslanov, Evgeniy and Cao, Wengang and Porvasnik, Stacy
and Namiki, Kazunori and Anai, Satoshi and Rosser, Charles J.},
title = {Bcl-2 mediated modulation of vascularization in prostate cancer xenografts},
journal = {Prostate},
year = {2009},
volume = {69},
pages = {459--470},
number = {5},
abstract = {Abstract 10.1002/pros.20888.abs PURPOSE We previously demonstrated
that Bcl-2 overexpression enhances the radiation resistance of PC-3
human prostate cancer cells and xenografts by inhibiting apoptosis,
increasing proliferation, and promoting angiogenesis. To further
elucidate the relationship between Bcl-2 expression and the angiogenic
potential of PC-3-Bcl-2 cells, tumorigenicity, angiogenesis, and
lymphangiogenesis were evaluated and compared in a Bcl-2 overexpressing
clone in vitro and in vivo. EXPERIMENTAL DESIGN Human prostate cancer
cells over expressing Bcl-2 were studied in vitro and in vivo to
determine the angiogenic and lymphangiogenic properties of these
cells. RESULTS Increased Bcl-2 expression enhanced the tumorigenicity
of prostate cancer xenografts. It also enhanced the expression and
secretion of key angiogenic and lymphangiogenic factors that stimulated
the synthesis of CD31-positive blood vessels and LYVE-1 positive
lymphatics. Specifically, the increased angiogenic and lymphangiogenic
potential correlated with increased serum levels of basic fibroblast
growth factor (bFGF), interleukin 8 (CXCL8), and matrix metalloproteinase
(MMP 9). In vitro analysis demonstrated that Bcl-2 expressing tumor
cells secreted bFGF and vascular endothelial growth factor (VEGF)
into culture supernatants. Microarray analysis of Bcl-2 expressing
PC-3 cells demonstrated increased transcription of genes involved
in metabolism, such as interleukins, growth factors, tumor necrosis
factors (TNF) family members, and peptidases. CONCLUSIONS Together,
these results demonstrate that Bcl-2 can regulate tumoral angiogenesis
and lymphangiogenesis and suggest that therapy targeted at Bcl-2
expression, angiogenesis, and lymphangiogenesis may synergistically
modulate tumor growth and confirm that Bcl-2 is a pivotal target
for cancer therapy. Prostate 69:459–470, 2009. © 2008 Wiley-Liss,
Inc.},
issn = {1097-0045},
keywords = {Bcl-2, microenvironment, vascular endothelial growth factor, basic
fibroblast growth factor, angiogenesis, lymphangiogenesis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20888}
}
@ARTICLE{Sakairi2007,
author = {Sakairi, Tetsuya and Okada, Miyoko and Ikeda, Itsuko and Utsumi,
Hiroyuki and Kohge, Shin and Sugimoto, Jiro and Sano, Fumiko and
Takagi, Shiro},
title = {Evaluation of gene expression related to hepatic cell maturation
and differentiation in a chemically induced mouse hepatoblastoma
cell line},
journal = {Experimental and Molecular Pathology},
year = {2007},
volume = {83},
pages = {419--427},
number = {3},
month = dec,
abstract = {The MHB-2 cell line, established from a mouse hepatoblastoma (HB),
was subjected to the reverse transcriptase-polymerase chain reaction
(RT-PCR) for evaluation of gene expression related to cell differentiation.
RNAs for c-kit, CD34, thy-1, albumin, cytokeratin (CK) 8, 18 and
19 could be detected, but expression of alpha-fetoprotein, glucose-6-phosphatase,
tyrosine aminotransferase and CK7 was not observed. MHB-2 cells were
positive for CK8/18 but negative for c-kit, CD34, thy-1 and albumin
on protein level. Immunohistochemical staining of the HB in vivo
revealed diffusely expressed c-kit. Thy-1-positive HB cells were
sparsely observed, but the tumor was negative for CD34 and rarely
positive for CK8/18. By in situ hybridization, the HB was positive
for CK18 but negative for CK19. Slight expression of albumin, but
the lack of immature hepatocytic marker suggested some heterogeneous
hepatocyte or an undifferentiated cell from other origin. Furthermore,
positive expression of CK19 as well as CK8 and CK18 in culture strongly
suggested the differentiation into a biliary lineage or the bidirectional
state. In conclusion, the present study indicated the mouse HB to
have de-differentiated, bipotent, or biliary-like cell characteristics,
and considering the histological difference between HB and biliary
tumors, it suggests the mouse HB cells are closely like some sort
of hepatic undifferentiated cells.},
issn = {0014-4800},
keywords = {Mouse, Hepatoblastoma, Gene expression, Differentiation},
url = {http://www.sciencedirect.com/science/article/B6WFB-4NYJ0XD-1/2/4204efc7ab2880da511b3cf4b29fd3ef}
}
@ARTICLE{Sakamaki2006,
author = {Sakamaki, Toshiyuki and Casimiro, Mathew C. and Ju, Xiaoming and
Quong, Andrew A. and Katiyar, Sanjay and Liu, Manran and Jiao, Xuanmao
and Li, Anping and Zhang, Xueping and Lu, Yinan and Wang, Chenguang
and Byers, Stephen and Nicholson, Robert and Link, Todd and Shemluck,
Melvin and Yang, Jianguo and Fricke, Stanley T. and Novikoff, Phyllis
M. and Papanikolaou, Alexandros and Arnold, Andrew and Albanese,
Christopher and Pestell, Richard},
title = {Cyclin D1 Determines Mitochondrial Function In Vivo},
journal = {Mol. Cell. Biol.},
year = {2006},
volume = {26},
pages = {5449--5469},
number = {14},
month = jul,
abstract = {The cyclin D1 gene encodes a regulatory subunit of the holoenzyme
that phosphorylates and inactivates the pRb tumor suppressor to promote
nuclear DNA synthesis. cyclin D1 is overexpressed in human breast
cancers and is sufficient for the development of murine mammary tumors.
Herein, cyclin D1 is shown to perform a novel function, inhibiting
mitochondrial function and size. Mitochondrial activity was enhanced
by genetic deletion or antisense or small interfering RNA to cyclin
D1. Global gene expression profiling and functional analysis of mammary
epithelial cell-targeted cyclin D1 antisense transgenics demonstrated
that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis
in vivo. Reciprocal regulation of these genes was observed in cyclin
D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA
synthesis and mitochondrial function.},
url = {http://mcb.asm.org/cgi/content/abstract/26/14/5449}
}
@ARTICLE{Sakamoto2005,
author = {Sakamoto, Chieko and Yamaguchi, Nobuyasu and Nasu, Masao},
title = {Rapid and Simple Quantification of Bacterial Cells by Using a Microfluidic
Device},
journal = {Appl. Envir. Microbiol.},
year = {2005},
volume = {71},
pages = {1117--1121},
number = {2},
month = feb,
abstract = {This study investigated a microfluidic chip-based system (on-chip
flow cytometry) for quantification of bacteria both in culture and
in environmental samples. Bacterial numbers determined by this technique
were similar to those obtained by direct microscopic count. The time
required for this on-chip flow cytometry was only 30 min per 6 samples.},
url = {http://aem.asm.org/cgi/content/abstract/71/2/1117}
}
@ARTICLE{Sakurai2004,
author = {Sakurai, Takeshi and Nakagawa, Takao and Mitsuno, Hidefumi and Mori,
Hajime and Endo, Yasuhisa and Tanoue, Shintarou and Yasukochi, Yuji
and Touhara, Kazushige and Nishioka, Takaaki},
title = {Identification and functional characterization of a sex pheromone
receptor in the silkmoth Bombyx mori},
journal = {PNAS},
year = {2004},
volume = {101},
pages = {16653--16658},
number = {47},
month = nov,
abstract = {Sex pheromones released by female moths are detected with high specificity
and sensitivity in the olfactory sensilla of antennae of conspecific
males. Bombykol in the silkmoth Bombyx mori was the first sex pheromone
to be identified. Here we identify a male-specific G protein-coupled
olfactory receptor gene, B. mori olfactory receptor 1 (BmOR-1), that
appears to encode a bombykol receptor. The BmOR-1 gene is located
on the Z sex chromosome, has an eight-exon/seven-intron structure,
and exhibits male-specific expression in the pheromone receptor neurons
of male moth antenna during late pupal and adult stages. Bombykol
stimulation of Xenopus laevis oocytes expressing BmOR-1 and BmG{alpha}q
elicited robust dose-dependent inward currents on two-electrode voltage
clamp recordings, demonstrating that the binding of bombykol to BmOR-1
leads to the activation of a BmG{alpha}q-mediated signaling cascade.
Antennae of female moths infected with BmOR-1-recombinant baculovirus
showed electrophysiological responses to bombykol but not to bombykal.
These results provide evidence that BmOR-1 is a G protein-coupled
sex pheromone receptor that recognizes bombykol.},
url = {http://www.pnas.org/cgi/content/abstract/101/47/16653}
}
@ARTICLE{Salajegheh2010,
author = {Salajegheh, Mohammad and Kong, Sek Won and Pinkus, Jack L. and Walsh,
Ronan J. and Liao, Anne and Nazareno, Remedios and Amato, Anthony
A. and Krastins, Bryan and Morehouse, Chris and Higgs, Brandon W.
and Jallal, Bahija and Yao, Yihong and Sarracino, David A. and Parker,
Kenneth C. and Greenberg, Steven A.},
title = {Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis
muscle with perifascicular atrophy},
journal = {Ann Neurol.},
year = {2010},
volume = {67},
pages = {53--63},
number = {1},
abstract = {Abstract 10.1002/ana.21805.abs Objective We investigated interferon-stimulated
gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and
its enzymatic pathway in dermatomyositis (DM), an autoimmune disease
primarily involving muscle and skin. Methods We generated microarray
data measuring transcript abundance for approximately 18,000 genes
in each of 113 human muscle biopsy specimens, and studied biopsy
specimens and cultured skeletal muscle using immunohistochemistry,
immunoblotting proteomics, real-time quantitative polymerase chain
reaction, and laser-capture microdissection. Results Transcripts
encoding ISG15-conjugation pathway proteins were markedly upregulated
in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold,
HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples.
Combined analysis with publicly available microarray datasets showed
that >50-fold ISG15 transcript elevation had 100% sensitivity and
specificity for 28 biopsies from adult DM-PFA and juvenile DM patients
compared with 199 muscle samples from other muscle diseases. Free
ISG15 and ISG15-conjugated proteins were only found on immunoblots
from DM-PFA muscle. Cultured human skeletal muscle exposed to type
1 interferons produced similar transcripts and ISG15 protein and
conjugates. Laser-capture microdissection followed by proteomic analysis
showed deficiency of titin in DM perifascicular atrophic myofibers.
Interpretation A large-scale microarray study of muscle samples demonstrated
that among a diverse group of muscle diseases DM was uniquely associated
with upregulation of the ISG15 conjugation pathway. Exposure of human
skeletal muscle cell culture to type 1 interferons produced a molecular
picture highly similar to that seen in human DM muscle. Perifascicular
atrophic myofibers in DM were deficient in a number of skeletal muscle
proteins including titin. ANN NEUROL 2010;67:53–63},
issn = {1531-8249},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ana.21805}
}
@ARTICLE{Salaria2006,
author = {Salaria, S. and Chana, G. and Caldara, F. and Feltrin, E. and Altieri,
M. and Faggioni, F. and Domenici, E. and Merlo-Pich, E. and Everall,
I.P.},
title = {Microarray analysis of cultured human brain aggregates following
cortisol exposure: Implications for cellular functions relevant to
mood disorders},
journal = {Neurobiology of Disease},
year = {2006},
volume = {23},
pages = {630--636},
number = {3},
month = sep,
abstract = {Increased cortisol levels in humans are often observed in patients
suffering from mood disorders. In this study human fetal brain aggregates
were exposed to cortisol at 500 nM for 3 weeks, as an in-vitro model
of chronic cortisol exposure. Microarray analysis on extracted mRNA
using the Affymetrix U133A platform was then performed. Our results
demonstrated a significant effect of cortisol on 1648 transcripts;
736 up-regulated and 912 down-regulated genes. The most differentially
regulated biological categories were: RNA processing, protein metabolism,
and cell growth. Within these categories we observed a down-regulation
of fibroblast growth factor 2 (FGF2) (-1.5-fold) and aquaporin4 (AQP4)
(-1.7-fold), alongside an up-regulation of fibroblast growth factor
9 (FGF9) (+1.7-fold) and vesicle associated membrane protein2 (VAMP2)
(+1.7-fold). FGF2, FGF9, AQP4 and VAMP2 changes were confirmed at
the protein level by immunohistochemistry. Alterations in FGF transcripts
are in keeping with recent literature demonstrating such effects
in patients with mood disorders.},
issn = {0969-9961},
keywords = {Human Fetal Brain Aggregates, Glucocorticoids, Gene Expression, Microarray
Analysis, Fibroblast Growth Factors, Mood Disorders},
url = {http://www.sciencedirect.com/science/article/B6WNK-4KF1HJF-1/2/3c76692c45cef7a7d5fb355ed154f683}
}
@ARTICLE{Salas2009,
author = {Salas, Sébastien and Jézéquel, Pascal and Campion, Loic and Deville,
Jean-Laurent and Chibon, Frédéric and Bartoli, Catherine and Gentet,
Jean-Claude and Charbonnel, Catherine and Gouraud, Wilfried and Voutsinos-Porche,
Brigitte and Brouchet, Anne and Duffaud, Florence and Figarella-Branger,
Dominique and Bouvier, Corinne},
title = {Molecular characterization of the response to chemotherapy in conventional
osteosarcomas: Predictive value of HSD17B10 and IFITM2},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {851--860},
number = {4},
abstract = {Abstract 10.1002/ijc.24457.abs The therapy regimen of high-grade osteosarcoma
includes chemotherapy followed by surgical resection and postoperative
chemotherapy. The degree of necrosis following definitive surgery
remains the only reliable prognostic factor and is used to guide
the choice of postoperative chemotherapy. The aim of this study was
to find molecular markers able to classify patients with an osteosarcoma
as good or poor responders to chemotherapy before beginning treatment.
Gene expression screening of 20 nonmetastatic high-grade osteosarcoma
patients was performed using cDNA microarray. Expression of selected
relevant genes was validated using QRT-PCR. Immunohistochemistry
on tissue microarrays sections of 73 biopsies was performed to investigate
protein expression. Fluorescent in situ hybridization was performed
for RPL8 gene. We have found that HSD17B10 gene expression was up-regulated
in poor responders and that immunohistochemistry expression of HSD17B10
on biopsy before treatment was correlatedto response to chemotherapy.
Other results include correlationof IFITM2, IFITM3, and RPL8 gene
expression to chemotherapy response. A statistical correlation was
found between polysomy 8 or gain of RPL8 and good response to chemotherapy.
These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes
are involved in the response to the chemotherapy and that HSD17B10
may be a therapeutic target. RPL8 and IFITM2 may be useful in the
assessment at diagnosis and for stratifying patients taking part
in randomized trials. © 2009 UICC},
issn = {1097-0215},
keywords = {conventional osteosarcoma, predictive markers, response to chemotherapy,
cDNA microarray, QRT-PCR, FISH, immunohistochemistry},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24457}
}
@ARTICLE{Salati2008,
author = {Salati, Simona and Zini, Roberta and Bianchi, Elisa and Testa, Anna
and Mavilio, Fulvio and Manfredini, Rossella and Ferrari, Sergio},
title = {Role of CD34 Antigen in Myeloid Differentiation of Human Hematopoietic
Progenitor Cells},
journal = {STEM CELLS},
year = {2008},
volume = {26},
pages = {950--959},
number = {4},
abstract = {Abstract 10.1634/stemcells.2007-0597.abs CD34 is a transmembrane protein
that is strongly expressed on hematopoietic stem/progenitor cells
(HSCs); despite its importance as a marker of HSCs, its function
is still poorly understood, although a role in cell adhesion has
been demonstrated. To characterize the function of CD34 antigen on
human HSCs, we examined, by both inhibition and overexpression, the
role of CD34 in the regulation of HSC lineage differentiation. Our
results demonstrate that CD34 silencing enhances HSC granulocyte
and megakaryocyte differentiation and reduces erythroid maturation.
In agreement with these results, the gene expression profile of these
cells reveals the upregulation of genes involved in granulocyte and
megakaryocyte differentiation and the downregulation of erythroid
genes. Consistently, retroviral-mediated CD34 overexpression leads
to a remarkable increase in erythroid progenitors and a dramatic
decrease in granulocyte progenitors, as evaluated by clonogenic assay.
Together, these data indicate that the CD34 molecule promotes the
differentiation of CD34+ hematopoietic progenitors toward the erythroid
lineage, which is achieved, at least in part, at the expense of granulocyte
and megakaryocyte lineages. Disclosure of potential conflicts of
interest is found at the end of this article.},
issn = {1549-4918},
keywords = {CD34 antigen, Hematopoietic stem cells, Hematopoietic progenitor cells,
Hematopoiesis, Myeloid differentiation, RNA interference},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-0597}
}
@ARTICLE{Salavati2006,
author = {Salavati, Reza and Ernst, Nancy Lewis and O'Rear, Jeff and Gilliam,
Troy and Tarun, Salvador, Jr. and Stuart, Kenneth},
title = {KREPA4, an RNA binding protein essential for editosome integrity
and survival of Trypanosoma brucei},
journal = {RNA},
year = {2006},
volume = {12},
pages = {819--831},
number = {5},
month = may,
abstract = {The 20S editosome, a multiprotein complex, catalyzes the editing of
most mitochondrial mRNAs in trypanosomatids by uridylate insertion
and deletion. RNAi mediated inactivation of expression of KREPA4
(previously TbMP24), a component of the 20S editosome, in procyclic
form Trypanosoma brucei resulted in inhibition of cell growth, loss
of RNA editing, and disappearance of 20S editosomes. Levels of MRP1
and REAP-1 proteins, which may have roles in editing but are not
editosome components, were unaffected. Tagged KREPA4 protein is incorporated
into 20S editosomes in vivo with no preference for either insertion
or deletion subcomplexes. Consistent with its S1-like motif, recombinant
KREPA4 protein binds synthetic gRNA with a preference for the 3'
oligo (U) tail. These data suggest that KREPA4 is an RNA binding
protein that may be specific for the gRNA Utail and also is important
for 20S editosome stability.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/12/5/819}
}
@ARTICLE{Salcedo2010,
author = {Salcedo, Rosalba and Worschech, Andrea and Cardone, Marco and Jones,
Yava and Gyulai, Zsofia and Dai, Ren-Ming and Wang, Ena and Ma, Winnie
and Haines, Diana and O'hUigin, Colm and Marincola, Francesco M.
and Trinchieri, Giorgio},
title = {MyD88-mediated signaling prevents development of adenocarcinomas
of the colon: role of interleukin 18},
journal = {J. Exp. Med.},
year = {2010},
volume = {207},
pages = {1625--1636},
number = {8},
month = aug,
abstract = {Signaling through the adaptor protein myeloid differentiation factor
88 (MyD88) promotes carcinogenesis in several cancer models. In contrast,
MyD88 signaling has a protective role in the development of azoxymethane
(AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC).
The inability of Myd88-/- mice to heal ulcers generated upon injury
creates an altered inflammatory environment that induces early alterations
in expression of genes encoding proinflammatory factors, as well
as pathways regulating cell proliferation, apoptosis, and DNA repair,
resulting in a dramatic increase in adenoma formation and progression
to infiltrating adenocarcinomas with frequent clonal mutations in
the {beta}-catenin gene. Others have reported that toll-like receptor
(Tlr) 4-deficient mice have a similar susceptibility to colitis to
Myd88-deficient mice but, unlike the latter, are resistant to CAC.
We have observed that mice deficient for Tlr2 or Il1r do not show
a differential susceptibility to colitis or CAC. However, upon AOM/DSS
treatment Il18-/- and Il18r1-/- mice were more susceptible to colitis
and polyp formation than wild-type mice, suggesting that the phenotype
of Myd88-/- mice is, in part, a result of their inability to signal
through the IL-18 receptor. This study revealed a previously unknown
level of complexity surrounding MyD88 activities downstream of different
receptors that impact tissue homeostasis and carcinogenesis.},
url = {http://jem.rupress.org/cgi/content/abstract/207/8/1625}
}
@ARTICLE{Saleh2011,
author = {Saleh, Leila and Otti, Gerlinde and Fiala, Christian and Pollheimer,
Jurgen and Knoefler, Martin},
title = {Evaluation of human first trimester decidual and telomerase-transformed
endometrial stromal cells as model systems of in vitro decidualization
},
journal = {Reproductive Biology and Endocrinology},
year = {2011},
volume = {9},
pages = {155},
number = {1},
abstract = {BACKGROUND:Decidualization, the differentiation process of maternal
uterine stromal cells into secretory decidual cells, is a prerequisite
for successful implantation and progression of pregnancy. For in
vitro differentiation mostly primary human endometrial stromal cells
(HESC) isolated from uterine samples after hysterectomy for benign
gynaecological diseases are utilised. However, a continuous supply
of endometrial tissue is often lacking. Hence, we analysed whether
cultivated human decidual stromal cells (HDSC) prepared from first
trimester pregnancy terminations may represent an alternative model
system for in vitro decidualization. Moreover, based on the expression
of critical marker genes these cells were compared to a previously
established endometrial stromal cell line during in vitro differentiation.METHODS:HDSC
isolated from decidual tissue attached to first trimester placentae,
and telomerase-transformed human endometrial stromal cells (THESC)
were characterised by immunofluorescence and differentiated in vitro
using either cyclic adenosine monophosphate (cAMP) and/or estrogen
(E2)/progesterone (P4). Proliferation was measured by analyzing cumulative
cell numbers. Expression of mRNAs encoding progesterone receptor
(PR), prolactin (PRL), insulin-like growth factor binding protein-1
(IGFBP1), and Dickkopf-1 (DKK1) was evaluated using quantitative
PCR after 3, 6, 9 and 12 days of in vitro differentiation. PRL and
IGFBP-1 protein expression was investigated by enzyme-linked immunosorbent
assay (ELISA) and Western blotting, respectively. Furthermore, forkhead
box O1A (FOXO1A), a critical transcription factor in decidualization,
was analysed by immunofluorescence and Western blotting at two different
time points of differentiation.RESULTS:Treatment with cAMP provoked
morphological changes and growth arrest of THESC and HDSC, the latter
showing loss of cells after 6 days of treatment. E2P4 stimulation
did neither affect cell morphology nor proliferation of THESC and
HDSC. Upon cAMP stimulation PR mRNA was suppressed in HDSC but not
in THESC, whereas E2P4 did not alter transcript levels in both cell
types. Protein expression of PR-A and PR-B was detectable in HDSC
and diminished under cAMP, whereas THESC failed to produce the nuclear
receptors. Supplementation of cAMP induced mRNA and protein expression
of PRL and IGFBP-1 in both cell types at day 3, 6, 9, and 12 of treatment.
In HDSC stimulation with E2P4 increased PRL and IGFBP-1 mRNA and
protein production, whereas hormone treatment did not induce the
two factors in THESC. E2P4 increased DKK1 mRNA at all time points
in HDSC and cAMP provoked induction at day 9 and 12 of differentiation.
In contrast, cAMP suppressed DKK1 mRNA in THESC, whereas E2P4 was
ineffective. In both cell types combined treatments with cAMP and
E2P4 provoked higher expression levels of PRL and IGFBP1 mRNA and
protein as compared to cAMP stimulation alone. FOXO1A protein and
its nuclear abundance were increased by cAMP in both cell types.
However, reduction of its nuclear localisation upon E2P4 treatment
could only be observed in HDSC.CONCLUSION:Both HDSC and THESC may
represent suitable model systems for cAMP-dependent in vitro decidualization.
Since cAMP decreases cell viability of HDSC after 6 days of incubation,
this substance should be preferentially used in short-term experiments.
Progesterone treatment of THESC might not be applicable since these
cells lack progesterone response and PR protein. In contrast, stimulation
of PR-expressing HDSC with E2P4 or cAMP/E2P4 may represent an appropriate
protocol for human in vitro decidualization inducing and maintaining
expression of critical marker genes in a time-dependent manner.},
url = {http://www.rbej.com/content/9/1/155}
}
@ARTICLE{Salem2010,
author = {Salem, Mohamed and Rexroad, Caird and Wang, Jiannan and Thorgaard,
Gary and Yao, Jianbo},
title = {Characterization of the rainbow trout transcriptome using Sanger
and 454-pyrosequencing approaches},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {564},
number = {1},
abstract = {BACKGROUND:Rainbow trout are important fish for aquaculture and recreational
fisheries and serves as a model species for research investigations
associated with carcinogenesis, comparative immunology, toxicology
and evolutionary biology. However, to date there is no genome reference
sequence to facilitate the development of molecular technologies
that utilize high-throughput characterizations of gene expression
and genetic variation. Alternatively, transcriptome sequencing is
a rapid and efficient means for gene discovery and genetic marker
development. Although a large number (258,973) of EST sequences are
publicly available, the nature of rainbow trout duplicated genome
hinders assembly and complicates annotation.RESULTS:High-throughput
deep sequencing of the Swanson rainbow trout doubled-haploid transcriptome
using 454-pyrosequencing technology yielded ~1.3 million reads with
an average length of 344 bp, a total of 447 million bases. De novo
assembly of the sequences yielded 151,847 Tentative Consensus (TC)
sequences (average length of 662 bp) and 224,391 singletons. A combination
assembly of both the 454-pyrosequencing ESTs and the pre-existing
sequences resulted in 161,818 TCs (average length of 758 bp) and
261,071 singletons. Gene Ontology analysis of the combination assembly
showed high similarities to transcriptomes of other fish species
with known genome sequences.CONCLUSION:The 454 library significantly
increased the suite of ESTs available for rainbow trout, allowing
improved assembly and annotation of the transcriptome. Furthermore,
the 454 sequencing enables functional genome research in rainbow
trout, providing a wealth of sequence data to serve as a reference
transcriptome for future studies including identification of paralogous
sequences and/or allelic variation, digital gene expression and proteomic
research.},
doi = {10.1186/1471-2164-11-564},
issn = {1471-2164},
pubmedid = {20942956},
url = {http://www.biomedcentral.com/1471-2164/11/564}
}
@ARTICLE{Salem2011,
author = {Salem, Tamer Z. and Zhang, Fengrui and Xie, Yan and Thiem, Suzanne
M.},
title = {Comprehensive analysis of host gene expression in Autographa californica
nucleopolyhedrovirus-infected Spodoptera frugiperda cells},
journal = {Virology},
year = {2011},
volume = {412},
pages = {167--178},
number = {1},
month = mar,
abstract = {Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is
the best-studied baculovirus and most commonly used virus vector
for baculovirus expression vector systems. The effect of AcMNPV infection
on host cells is incompletely understood. A microarray based on Spodoptera
frugiperda ESTs was used to investigate the impact of AcMNPV on host
gene expression in cultured S. frugiperda, Sf21 cells. Most host
genes were down-regulated over the time course of infection, although
a small number were up-regulated. The most highly up-regulated genes
encoded heat shock protein 70s and several poorly characterized proteins.
Regulated genes with the highest score identified by functional annotation
clustering included primarily products required for protein expression
and trafficking in the ER and golgi. All were significantly down-regulated
by approximately 12 h post-infection. Microarray data were validated
by qRT-PCR. This study provides the first comprehensive host transcriptome
overview of Sf21 cells during AcMNPV infection.},
issn = {0042-6822},
keywords = {Microarray, AcMNPV, Sf21 cells, Baculovirus, Host genes, qRT-PCR,
Hsp 70, DAVID, Transcriptome},
url = {http://www.sciencedirect.com/science/article/pii/S0042682211000110}
}
@ARTICLE{Salerno2011,
author = {Salerno, Paolo and Garcia-Rostan, Ginesa and Piccinin, Sara and Bencivenga,
Tammaro Claudio and Di Maro, Gennaro and Doglioni, Claudio and Basolo,
Fulvio and Maestro, Roberta and Fusco, Alfredo and Santoro, Massimo
and Salvatore, Giuliana},
title = {TWIST1 Plays a Pleiotropic Role in Determining the Anaplastic Thyroid
Cancer Phenotype},
journal = {J. Clin. Endocrinol. Metab.},
year = {2011},
volume = {96},
pages = {E772--781},
number = {5},
month = may,
abstract = {ContextAnaplastic thyroid carcinoma (ATC) is one of the most aggressive
human tumors; it is characterized by chemoresistance, local invasion,
and distant metastases. ATC is invariably fatal. ObjectiveThe aim
was to study the role of TWIST1, a basic helix-loop-helix transcription
factor, in ATC. DesignExpression of TWIST1 was studied by immunohistochemistry
and real-time PCR in normal thyroids and well-differentiated, poorly
differentiated, and ATC. The function of TWIST1 was studied by RNA
interference in ATC cells and by ectopic expression in well-differentiated
thyroid carcinoma cells. ResultsATCs up-regulate TWIST1 with respect
to normal thyroids as well as to poorly and well-differentiated thyroid
carcinomas. Knockdown of TWIST1 by RNA interference in ATC cells
reduced cell migration and invasion and increased sensitivity to
apoptosis. The ectopic expression of TWIST1 in thyroid cells induced
resistance to apoptosis and increased cell migration and invasion.
ConclusionsTWIST1 plays a key role in determining malignant features
of the anaplastic phenotype in vitro.},
comment = {10.1210/jc.2010-1182},
url = {http://jcem.endojournals.org/cgi/content/abstract/96/5/E772}
}
@ARTICLE{Saletta2010,
author = {Saletta, Federica and Suryo Rahmanto, Yohan and Noulsri, Egarit and
Richardson, Des R.},
title = {Iron Chelator-Mediated Alterations in Gene Expression: Identification
of Novel Iron-Regulated Molecules That Are Molecular Targets of Hypoxia-Inducible
Factor-1{alpha} and p53},
journal = {Mol. Pharmacol.},
year = {2010},
volume = {77},
pages = {443--458},
number = {3},
month = mar,
abstract = {Iron deficiency affects 500 million people, yet the molecular role
of iron in gene expression remains poorly characterized. In addition,
the alterations in global gene expression after iron chelation remain
unclear and are important to assess for understanding the molecular
pathology of iron deficiency and the biological effects of chelators.
Considering this, we assessed the effect on whole genome gene expression
of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde
isonicotinoyl hydrazone) that have markedly different permeability
properties. Sixteen genes were significantly regulated by both ligands,
whereas a further 50 genes were significantly regulated by either
compound. Apart from iron-mediated regulation of expression via hypoxia
inducible factor-1{alpha}, it was noteworthy that the transcription
factor p53 was also involved in iron-regulated gene expression. Examining
16 genes regulated by both chelators in normal and neoplastic cells,
five genes (APP, GDF15, CITED2, EGR1, and PNRC1) were significantly
differentially expressed between the cell types. In view of their
functions in tumor suppression, proliferation, and apoptosis, these
findings are important for understanding the selective antiproliferative
effects of chelators against neoplastic cells. Most of the genes
identified have not been described previously to be iron-regulated
and are important for understanding the molecular and cellular effects
of iron depletion.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/77/3/443}
}
@ARTICLE{Salhab2011,
author = {Salhab, M. and Tosca, L. and Cabau, C. and Papillier, P. and Perreau,
C. and Dupont, J. and Mermillod, P. and Uzbekova, S.},
title = {Kinetics of gene expression and signaling in bovine cumulus cells
throughout IVM in different mediums in relation to oocyte developmental
competence, cumulus apoptosis and progesterone secretion},
journal = {Theriogenology},
year = {2011},
volume = {75},
pages = {90--104},
number = {1},
month = jan,
abstract = {In vitro maturation of oocytes is a crucial step in assisted reproductive
technologies in cattle; however, the molecular mechanisms of cumulus
contribution to oocyte developmental potential require more investigation.
Based on transcriptomic data, we studied by using real-time RT-PCR
and western blot in bovine cumulus cells, the kinetics of expression
of several candidate genes involved in oxidative stress response,
apoptosis, steroid metabolism and signal transmission throughout
IVM. Phosphorylations of the components of the main signaling pathways
were also analyzed. In addition, IVM was performed in different maturation
mediums which influenced the cumulus apoptosis, progesterone secretion
and oocyte developmental competence. Glutathione-S-transferase A1
(GSTA1) transcript and protein abundance significantly decreased
throughout IVM progression. Similarly, transcript levels of FSH receptor
and aromatase (CYP19A1) and protein levels of three steroidogenic
enzymes (steroidogenic acute regulatory protein, cytochrome P450scc
and 3-beta-hydroxysteroid dehydrogenase) decreased along with progression
of maturation and especially since 10 hours of IVM. Expression of
progesterone receptor (PGR) and clusterin (CLU) mRNA and phosphorylations
of protein kinases AKT, MAPK P38 and SMAD2 were particularly increased
at 10 hours of IVM. This expression pattern supposed the role of
these factors during oocyte metaphase-I check point of meiosis. Levels
of CLU, GSTA1 and FSHR transcripts were higher in 199 basic hormone-free
medium as compared to the medium 199EM, enriched in gonadotropins
and growth factors, in which we recorded the higher developmental
rate and progesterone secretion. Higher phosphorylation levels of
SMAD2, AKT and MAP kinase JNK1, but not of MAP kinases ERK1/ERK2
or P38, was positively correlated with oocyte developmental competence
and progesterone secretion and negatively correlated with cumulus
apoptosis rate. These factors and signaling pathways in cumulus cells
are potentially involved in controlling different stages of oocyte
nuclear maturation and acquirement of its developmental potential.},
issn = {0093-691X},
keywords = {Cow, Oocyte maturation, Cumulus, GSTA1, Clusterin, SMAD2, MAP kinase},
url = {http://www.sciencedirect.com/science/article/pii/S0093691X10003912}
}
@ARTICLE{Salhia2008,
author = {Salhia, Bodour and Tran, Nhan L. and Chan, Amanda and Wolf, Amparo
and Nakada, Mitsutoshi and Rutka, Fiona and Ennis, Matthew and McDonough,
Wendy S. and Berens, Michael E. and Symons, Marc and Rutka, James
T.},
title = {The Guanine Nucleotide Exchange Factors Trio, Ect2, and Vav3 Mediate
the Invasive Behavior of Glioblastoma},
journal = {Am. J. Pathol.},
year = {2008},
volume = {173},
pages = {1828--1838},
number = {6},
month = dec,
abstract = {Malignant gliomas are characterized by their ability to invade normal
brain tissue. We have previously shown that the small GTPase Rac1
plays a role in both migration and invasion in gliomas. Here, we
aim to identify Rac-activating guanine nucleotide exchange factors
(GEFs) that mediate glioblastoma invasiveness. Using a brain tumor
expression database, we identified three GEFs, Trio, Ect2, and Vav3,
that are expressed at higher levels in glioblastoma versus low-grade
glioma. The expression of these GEFs is also associated with poor
patient survival. Quantitative real-time polymerase chain reaction
and immunohistochemical analyses on an independent set of tumors
confirmed that these GEFs are overexpressed in glioblastoma as compared
with either nonneoplastic brain or low-grade gliomas. In addition,
depletion of Trio, Ect2, and Vav3 by siRNA oligonucleotides suppresses
glioblastoma cell migration and invasion. Depletion of either Ect2
or Trio also reduces the rate of cell proliferation. These results
suggest that targeting GEFs may present novel strategies for anti-invasive
therapy for malignant gliomas.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/173/6/1828}
}
@ARTICLE{Salilew-Wondim2010,
author = {Salilew-Wondim, Dessie and Holker, Michael and Rings, Franca and
Ghanem, Nasser and Ulas-Cinar, Mehmet and Peippo, Jaana and Tholen,
Ernst and Looft, Christian and Schellander, Karl and Tesfaye, Dawit},
title = {Bovine pretransfer endometrium and embryo transcriptome fingerprints
as predictors of pregnancy success after embryo transfer},
journal = {Physiol Genomics},
year = {2010},
volume = {42},
pages = {201--218},
number = {2},
month = jul,
abstract = {Aberrant gene expression in the uterine endometrium and embryo has
been the major causes of pregnancy failure in cattle. However, selecting
cows having adequate endometrial receptivity and embryos of better
developmental competence based on the gene expression pattern has
been a greater challenge. To investigate whether pretransfer endometrial
and embryo gene expression pattern has a direct relation with upcoming
pregnancy success, we performed a global endometrial and embryo transcriptome
analysis using endometrial and embryo biopsy technology and the pregnancy
outcome information. For this, endometrial samples were collected
from Simmental heifers at day 7 and 14 of the estrous cycle, one
cycle prior to embryo transfer. In the next cycle, blastocyst stage
embryos were transferred to recipients at day 7 of the estrous cycle
after taking 30-40% of the blastocyst as a biopsy for transcriptome
analysis. The results revealed that at day 7 of the estrous cycle,
the endometrial gene expression pattern of heifers whose pregnancy
resulting in calf delivery was significantly different compared with
those resulting in no pregnancy. These differences were accompanied
by qualitative and quantitative alteration of major biological process
and molecular pathways. However, the transcriptome difference was
minimal between the two groups of animals at day 14 of the estrous
cycle. Similarly, the transcriptome analysis between embryos biopsies
that resulted in calf delivery and those resulted in no pregnancy
revealed a total of 70 differentially expressed genes. Among these,
the transcript levels of 32 genes including SPAG17, PF6, UBE2D3P,
DFNB31, AMD1, DTNBP1, and ARL8B were higher in embryo biopsies resulting
in calf delivery. Therefore, the present study highlights the potential
of pretransfer endometrial and embryo gene expression patterns as
predictors of pregnancy success in cattle.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42/2/201}
}
@ARTICLE{Salimullah2011,
author = {Salimullah, Md and Mizuho, Sakai and Plessy, Charles and Carninci,
Piero},
title = {NanoCAGE: A High-Resolution Technique to Discover and Interrogate
Cell Transcriptomes},
journal = {Cold Spring Harb Protoc},
year = {2011},
volume = {2011},
pages = {pdb.prot5559--},
number = {1},
month = jan,
abstract = {Cap analysis gene expression (CAGE) is a method to identify the 5'
ends of transcripts, allowing the discovery of new promoters and
the quantification of gene activity. Combining promoter location
and their expression levels, CAGE data are essential for annotation-agnostic
studies of regulatory gene networks. However, CAGE requires large
amounts of input RNA, which usually are not obtainable from highly
refined samples such as tissue microdissections or subcellular fractions.
The nanoCAGE method can capture the 5' ends of transcripts from as
little as 10 ng of total RNA and takes advantage of the capacity
of current sequencers to produce longer (50-100 bp) reads. The method
prepares cap-selected cDNAs ready for direct sequencing of their
5' ends (optionally mate-paired with the 3' end) that can provide
information about downstream sequences. This protocol describes how
to prepare nanoCAGE libraries from as little as 50 ng of total RNA
within two working days. The libraries can be sequenced using an
Illumina Gene AmplifierIIx with a level of sensitivity 1000 times
higher than CAGE.},
comment = {10.1101/pdb.prot5559},
url = {http://cshprotocols.cshlp.org/cgi/content/abstract/2011/1/pdb.prot5559}
}
@ARTICLE{Salome2009,
author = {Salome, N. and Hansson, C. and Taube, M. and Gustafsson-Ericson,
L. and Egecioglu, E. and Karlsson-Lindahl, L. and Fehrentz, J. A.
and Martinez, J. and Perrissoud, D. and Dickson, S. L.},
title = {On the Central Mechanism Underlying Ghrelin´s Chronic Pro-Obesity
Effects in Rats: New Insights from Studies Exploiting a Potent Ghrelin
Receptor Antagonist},
journal = {Journal of Neuroendocrinology},
year = {2009},
volume = {21},
pages = {777--785},
number = {9},
abstract = {In the present study, we explore the central nervous system mechanism
underlying the chronic central effects of ghrelin with respect to
increasing body weight and body fat. Specifically, using a recently
developed ghrelin receptor antagonist, GHS-R1A (JMV2959), we investigate
the role of GHS-R1A in mediating the effects of ghrelin on energy
balance and on hypothalamic gene expression. As expected, in adult
male rats, chronic central treatment with ghrelin for 14Â days, when
compared to vehicle-treated control rats, resulted in an increased
body weight, lean mass and fat mass (assessed by dual X-ray absorptiometry),
dissected white fat pad weight, cumulative food intake, food efficiency,
respiratory exchange ratio and a decrease of energy expenditure.
Co-administration of the ghrelin receptor antagonist JMV2959 suppressed/blocked
the majority of these effects, with the notable exception of ghrelin-induced
food intake and food efficiency. The hypothesis emerging from these
data, namely that GHS-R1A mediates the chronic effects of ghrelin
on fat accumulation, at least partly independent of food intake,
is discussed in light of the accompanying data regarding the hypothalamic
genes coding for peptides and receptors involved in energy balance
regulation, which were found to have altered expression in these
studies.},
issn = {1365-2826},
keywords = {growth hormone secretagogue, hypothalamus, ghrelin antagonist, energy
expenditure, appetite, food intake},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2826.2009.01895.x}
}
@ARTICLE{Salome2011,
author = {Salomé, Nicolas and Taube, Magdalena and Egecioglu, Emil and Hansson,
Caroline and Stenström, Björn and Chen, Duan and Andersson, Daniel
R. and Georg Kuhn, H. and Ohlsson, Claes and Dickson, Suzanne L.},
title = {Gastrectomy alters emotional reactivity in rats: neurobiological
mechanisms},
journal = {European Journal of Neuroscience},
year = {2011},
volume = {33},
pages = {1685--1695},
number = {9},
abstract = {Abstract Gastrectomy (Gsx) is associated with altered emotional function
and a predisposition to depression/anxiety disorders. Here we investigated
the effects of Gsx on emotional reactivity in rats and explored the
underlying neurobiological mechanisms. Gsx- and sham-operated rats
were exposed to behavioural tests that explore anxiety- and depression-like
behaviour (open field, black and white box, elevated plus maze, social
interaction, forced swim) as well as memory (object recognition).
The potential neurobiological mechanisms underlying these differences
were explored by measuring (i) turnover of candidate neurotransmitter
systems in the nucleus accumbens, (ii) hippocampal neurogenesis by
BrdU labelling or by analysis of candidate genes involved in neuronal
growth and (iii) changes in mRNA expression of candidate genes in
dissected hippocampal and amygdala tissue. Data from individual behavioural
tests as well as from multivariate analysis revealed differing emotional
reactivity between Gsx- and sham-operated rats. Gsx rats showed reduced
emotional reactivity in a new environment and decreased depression-like
behaviour. Accumbal serotonin and dopamine turnover were both reduced
in Gsx rats. Gsx also led to a memory deficit, although hippocampal
neurogenesis was unaffected. Of the many candidate genes studied
by real-time RT-PCR, we highlight a Gsx-associated decrease in expression
of Egr-1, a transcription factor linked to neural plasticity and
cognition, in the hippocampus and amygdala. Thus, Gsx induces an
alteration of emotional reactivity and a memory/cognitive deficit
that is associated with reduced turnover of serotonin and dopamine
in the nucleus accumbens and decreased expression of Egr-1 in the
hippocampus and amygdala.},
doi = {10.1111/j.1460-9568.2011.07640.x},
issn = {1460-9568},
keywords = {anxiety, depression, gastric surgery, gut hormones},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2011.07640.x}
}
@ARTICLE{Salunkhe2010,
author = {Salunkhe, S and Soorapaneni, S and Prasad, KS and Raiker, VA and
Padmanabhan, S},
title = {Strategies to maximize expression of rightly processed human interferon
alpha2b in Pichia pastoris.},
journal = {Protein Exp Purif.},
year = {2010},
volume = {71},
pages = {139-46--},
number = {2},
month = jun,
abstract = {The human interferon alpha 2b (IFN alpha2b) belongs to the interferon
family of cytokines that exerts many biological functions like inhibition
of virus multiplication, repression of tumour growth and other immunological
functions. Herein, a synthetic gene coding for human IFN alpha2b
was cloned and integrated into a methylotropic yeast-Pichiapastoris.
The recombinant human IFN alpha2b protein (approximately 19kDa) could
be successfully expressed in Pichiapastoris to a level of nearly
300mg/L with nearly 93% recovery on purification using a single anion
exchange chromatography step. A novel media component dimethyl sulphoxide
(DMSO) was found to aid in expression of rightly processed IFN alpha2b
form with dramatic reduction in the expression of a 20kDa IFN isoform
contaminant frequently observed by other workers. The identity of
the 20kDa isoform was confirmed by N terminal sequencing which showed
extra eleven amino acids at the N terminal portion of the IFN molecule
obtained due to incorrect processing by the host KEX2 protease. The
purified IFN alpha2b (19kDa) preparation was confirmed by N terminal
sequencing, and characterized by MALDI-TOF and Agilent 2100 Bioanalyzer.
The bioassay of the recombinant protein gave a specific activity
of >2x10(8)IU/mg.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20159042}
}
@ARTICLE{Salvagiotto2008,
author = {Salvagiotto, Giorgia and Zhao, Yun and Vodyanik, Maxim and Ruotti,
Victor and Stewart, Ronald and Marra, Marco and Thomson, James and
Eaves, Connie and Slukvin, Igor},
title = {Molecular profiling reveals similarities and differences between
primitive subsets of hematopoietic cells generated in vitro from
human embryonic stem cells and in vivo during embryogenesis},
journal = {Experimental Hematology},
year = {2008},
volume = {36},
pages = {1377--1389},
number = {10},
month = oct,
abstract = {Objective Cellular and molecular changes that occur during the genesis
of the hematopoietic system and hematopoietic stem cells in the human
embryo are mostly inaccessible to study and remain poorly understood.
To address this gap we have exploited the human embryonic stem cell
(hESC) system to molecularly characterize the global transcriptomes
of the two functionally discreet and phenotypically separable populations
of multipotent hematopoietic cells that first appear when hESCs are
induced to differentiate on OP9 cells.Materials and Methods We prepared
long serial analysis of gene expression libraries from lin-CD34+CD43+CD45-
and lin-CD34+CD43+CD45+ subsets of primitive hematopoietic cells
derived in vitro from hESCs, sequenced them to a depth of 200,000
tags and compared their content with similar libraries prepared from
highly purified populations of very primitive human fetal liver and
cord blood hematopoietic cells.Results Comparison of libraries obtained
from hESC-derived lin-CD34+CD43+CD45- and lin-CD34+CD43+CD45+ revealed
differences in their expression of genes associated with myeloid
development, cellular biosynthetic processes, and cell-cycle regulation.
Further comparisons with analogous data for primitive hematopoietic
cells isolated from first-trimester human fetal liver and newborn
cord blood showed an apparent similarity between the transcriptomes
of the most primitive hESC- and in vivo-derived populations, with
the main differences involving genes that regulate HSC self-renewal
and homing, chromatin remodeling, AP1 transcription complex genes,
and noncoding RNAs.Conclusion These data suggest that primitive hematopoietic
cells are generated from hESCs in vitro by processes similar to those
operative during human embryogenesis in vivo, although some differences
were also detected.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4THBXHN-2/2/dc045c24b06ec15407c2feebeba53a74}
}
@ARTICLE{Salvesen2009,
author = {Salvesen, H. B. and Carter, S. L. and Mannelqvist, M. and Dutt, A.
and Getz, G. and Stefansson, I. M. and Raeder, M. B. and Sos, M.
L. and Engelsen, I. B. and Trovik, J. and Wik, E. and Greulich, H.
and Bo, T. H. and Jonassen, I. and Thomas, R. K. and Zander, T. and
Garraway, L. A. and Oyan, A. M. and Sellers, W. R. and Kalland, K.
H. and Meyerson, M. and Akslen, L. A. and Beroukhim, R.},
title = {Integrated genomic profiling of endometrial carcinoma associates
aggressive tumors with indicators of PI3 kinase activation},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {4834--4839},
number = {12},
month = mar,
abstract = {Although 75% of endometrial cancers are treated at an early stage,
15% to 20% of these recur. We performed an integrated analysis of
genome-wide expression and copy-number data for primary endometrial
carcinomas with extensive clinical and histopathological data to
detect features predictive of recurrent disease. Unsupervised analysis
of the expression data distinguished 2 major clusters with strikingly
different phenotypes, including significant differences in disease-free
survival. To identify possible mechanisms for these differences,
we performed a global genomic survey of amplifications, deletions,
and loss of heterozygosity, which identified 11 significantly amplified
and 13 significantly deleted regions. Amplifications of 3q26.32 harboring
the oncogene PIK3CA were associated with poor prognosis and segregated
with the aggressive transcriptional cluster. Moreover, samples with
PIK3CA amplification carried signatures associated with in vitro
activation of PI3 kinase (PI3K), a signature that was shared by aggressive
tumors without PIK3CA amplification. Tumors with loss of PTEN expression
or PIK3CA overexpression that did not have PIK3CA amplification also
shared the PI3K activation signature, high protein expression of
the PI3K pathway member STMN1, and an aggressive phenotype in test
and validation datasets. However, mutations of PTEN or PIK3CA were
not associated with the same expression profile or aggressive phenotype.
STMN1 expression had independent prognostic value. The results affirm
the utility of systematic characterization of the cancer genome in
clinically annotated specimens and suggest the particular importance
of the PI3K pathway in patients who have aggressive endometrial cancer.},
url = {http://www.pnas.org/cgi/content/abstract/106/12/4834}
}
@ARTICLE{Salvestrini2012,
author = {Salvestrini, Valentina and Zini, Roberta and Rossi, Lara and Gulinelli,
Sara and Manfredini, Rossella and Bianchi, Elisa and Piacibello,
Wanda and Caione, Luisa and Migliardi, Giorgia and Ricciardi, Maria
Rosaria and Tafuri, Agostino and Romano, Marco and Salati, Simona
and Di Virgilio, Francesco and Ferrari, Sergio and Baccarani, Michele
and Ferrari, Davide and Lemoli, Roberto M.},
title = {Purinergic signaling inhibits human acute myeloblastic leukemia cell
proliferation, migration, and engraftment in immunodeficient mice},
journal = {Blood},
year = {2012},
volume = {119},
pages = {217-226},
number = {1},
abstract = {Extracellular ATP and UTP nucleotides increase the proliferation and
engraftment potential of normal human hematopoietic stem cells via
the engagement of purinergic receptors (P2Rs). In the present study,
we show that ATP and UTP have strikingly opposite effects on human
acute myeloblastic leukemia (AML) cells. Leukemic cells express P2Rs.
ATP-stimulated leukemic cells, but not normal CD34+ cells, undergo
down-regulation of genes involved in cell proliferation and migration,
whereas cell-cycle inhibitors are up-regulated. Functionally, ATP
induced the inhibition of proliferation and accumulation of AML cells,
but not of normal cells, in the G0 phase of the cell cycle. Exposure
to ATP or UTP inhibited AML-cell migration in vitro. In vivo, xenotransplantation
experiments demonstrated that the homing and engraftment capacity
of AML blasts and CD34+CD38- cells to immunodeficient mice BM was
significantly inhibited by pretreatment with nucleotides. P2R-expression
analysis and pharmacologic profiling suggested that the inhibition
of proliferation by ATP was mediated by the down-regulation of the
P2X7R, which is up-regulated on untreated blasts, whereas the inhibition
of chemotaxis was mainly mediated via P2Y2R and P2Y4R subtypes. We
conclude that, unlike normal cells, P2R signaling inhibits leukemic
cells and therefore its pharmacologic modulation may represent a
novel therapeutic strategy.},
doi = {10.1182/blood-2011-07-370775},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/119/1/217.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/119/1/217}
}
@ARTICLE{Salvi2009,
author = {Salvi, Alessandro and Sabelli, Cristiano and Moncini, Silvia and
Venturin, Marco and Arici, Bruna and Riva, Paola and Portolani, Nazario
and Giulini, Stefano M. and De Petro, Giuseppina and Barlati, Sergio},
title = {MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased
migration of human hepatocellular carcinoma cells},
journal = {FEBS Journal},
year = {2009},
volume = {276},
pages = {2966--2982},
number = {11},
abstract = {Urokinase-type plasminogen activator (uPA) and c-met play a major
role in cancer invasion and metastasis. Evidence has suggested that
uPA and c-met overexpression may be coordinated in human hepatocellular
carcinoma (HCC). In the present study, to understand whether the
expression of these genes might be coregulated by specific microRNAs
(miRs) in human cells, we predicted that Homo sapiens microRNA-23b
could recognize two sites in the 3′-UTR of uPA and four sites in
the c-met 3′-UTR by the algorithm pictar. The miR-23b expression
analysis in human tumor and normal cells revealed an inverse trend
with uPA and c-met expression, indicating that uPA and c-met negative
regulation might depend on miR-23b expression. Transfection of miR-23b
molecules in HCC cells (SKHep1C3) led to inhibition of protein expression
of the target genes and caused a decrease in cell migration and proliferation
capabilities. Furthermore, anti-miR-23b transfection in human normal
AB2 dermal fibroblasts upregulated the expression of endogenous uPA
and c-met. Cotransfection experiments in HCC cells of the miR-23b
with pGL4.71 Renilla luciferase reporter gene constructs, containing
the putative uPA and c-met 3′-UTR target sites, and with the pGL3
firefly luciferase-expressing vector showed a decrease in the relative
luciferase activity. This would indicate that miR-23b can recognize
target sites in the 3′-UTR of uPA and of c-met mRNAs and translationally
repress the expression of uPA and c-met in HCC cells. The evidence
obtained shows that overexpression of miR-23b leads to uPA and c-met
downregulation and to decreased migration and proliferation abilities
of HCC cells.},
issn = {1742-4658},
keywords = {c-met, hepatocellular carcinoma cells, microRNA-23b, urokinase},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1742-4658.2009.07014.x}
}
@ARTICLE{Salvo-Chirnside2011,
author = {Salvo-Chirnside, Eliane and Kane, Steven and Kerr, Lorraine},
title = {Protocol: High throughput silica-based purification of RNA from Arabidopsis
seedlings in a 96-well format.},
journal = {Plant Methods},
year = {2011},
volume = {7},
pages = {40},
number = {1},
abstract = {The increasing popularity of systems-based approaches to plant research
has resulted in a demand for high throughput (HTP) methods to be
developed. RNA extraction from multiple samples in an experiment
is a significant bottleneck in performing systems-level genomic studies.
Therefore we have established a high throughput method of RNA extraction
from Arabidopsis thaliana to facilitate gene expression studies in
this widely used plant model. We present optimised manual and automated
protocols for the extraction of total RNA from 9-day-old Arabidopsis
seedlings in a 96 well plate format using silica membrane-based methodology.
Consistent and reproducible yields of high quality RNA are isolated
averaging 8.9 ug total RNA per sample (~20 mg plant tissue). The
purified RNA is suitable for subsequent qPCR analysis of the expression
of over 500 genes in triplicate from each sample. Using the automated
procedure, 192 samples (2x 96 well plates) can easily be fully processed
(samples homogenised, RNA purified and quantified) in less than half
a day. Additionally we demonstrate that plant samples can be stored
in RNAlater at -20 degrees C (but not 4 degrees C) for 10 months
prior to extraction with no significant effect on RNA yield or quality.
Additionally, disrupted samples can be stored in the lysis buffer
at -20 degrees C for at least 6 months prior to completion of the
extraction procedure providing a flexible sampling and storage scheme
to facilitate complex time series experiments.},
doi = {10.1186/1746-4811-7-40},
issn = {1746-4811},
pubmedid = {22136293},
url = {http://www.plantmethods.com/content/7/1/40}
}
@ARTICLE{Salzmann2012,
author = {Salzmann, Annick and Guipponi, Michel and Lyons, Peter J. and Fricker,
Lloyd D. and Sapio, Matthew and Lambercy, Carmen and Buresi, Catherine
and Ouled Amar Bencheikh, Bouchra and Lahjouji, Fatiha and Ouazzani,
Reda and Crespel, Arielle and Chaigne, Denys and Malafosse, Alain},
title = {Carboxypeptidase A6 gene (CPA6) mutations in a recessive familial
form of febrile seizures and temporal lobe epilepsy and in sporadic
temporal lobe epilepsy},
journal = {Human Mutation},
year = {2012},
volume = {33},
pages = {124--135},
number = {1},
abstract = {Febrile seizures (FS) and temporal lobe epilepsy (TLE) were found
in four of the seven siblings born to healthy Moroccan consanguineous
parents. We hypothesized autosomal recessive (AR) inheritance. Combined
linkage analysis and autozygosity mapping of a genome-wide single
nucleotide polymorphism genotyping identified a unique identical
by descent (IBD) locus of 9.6 Mb on human chromosome 8q12.1-q13.2.
Sequencing of the 38 genes mapped within the linked interval revealed
a homozygous missense mutation c.809C>T (p.Ala270Val) in the carboxypeptidase
A6 gene (CPA6). Screening all exons of CPA6 in unrelated patients
with partial epilepsy (n = 195) and FS (n = 145) revealed a new heterozygous
missense mutation c.799G>A (p.Gly267Arg) in three TLE patients. Structural
modeling of CPA6 indicated that both mutations are located near the
enzyme's active site. In contrast to wild-type CPA6, which is secreted
and binds to the extracellular matrix where it is enzymatically active,
Ala270Val CPA6 was secreted at about 40% of the level of the wild-type
CPA6 and was fully active, while Gly267Arg CPA6 was not detected
in the medium or extracellular matrix. This study suggests that CPA6
is genetically linked to an AR familial form of FS and TLE, and is
associated with sporadic TLE cases. Hum Mutat 33:124–135, 2012.
© 2011 Wiley Periodicals, Inc.},
doi = {10.1002/humu.21613},
issn = {1098-1004},
keywords = {Febrile seizures, temporal lobe epilepsy, linkage analysis, autosomal
recessive, autozygosity mapping, CPA6},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.21613}
}
@ARTICLE{Samanta2006,
author = {Samanta, Manoj Pratim and Tongprasit, Waraporn and Sethi, Himanshu
and Chin, Chen-Shan and Stolc, Viktor},
title = {Global identification of noncoding RNAs in Saccharomyces cerevisiae
by modulating an essential RNA processing pathway},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {4192--4197},
number = {11},
month = mar,
abstract = {Noncoding RNAs (ncRNAs) perform essential cellular tasks and play
key regulatory roles in all organisms. Although several new ncRNAs
in yeast were recently discovered by individual studies, to our knowledge
no comprehensive empirical search has been conducted. We demonstrate
a powerful and versatile method for global identification of previously
undescribed ncRNAs by modulating an essential RNA processing pathway
through the depletion of a key ribonucleoprotein enzyme component,
and monitoring differential transcriptional activities with genome
tiling arrays during the time course of the ribonucleoprotein depletion.
The entire Saccharomyces cerevisiae genome was scanned during cell
growth decay regulated by promoter-mediated depletion of Rpp1, an
essential and functionally conserved protein component of the RNase
P enzyme. In addition to most verified genes and ncRNAs, expression
was detected in 98 antisense and intergenic regions, 74 that were
further confirmed to contain previously undescribed RNAs. A class
of ncRNAs, located antisense to coding regions of verified protein-coding
genes, is discussed in this article. One member, HRA1, is likely
involved in 18S rRNA maturation.},
url = {http://www.pnas.org/cgi/content/abstract/103/11/4192}
}
@ARTICLE{Sambanthamoorthy2006,
author = {Sambanthamoorthy, Karthik and Smeltzer, Mark S. and Elasri, Mohamed
O.},
title = {Identification and characterization of msa (SA1233), a gene involved
in expression of SarA and several virulence factors in Staphylococcus
aureus},
journal = {Microbiology},
year = {2006},
volume = {152},
pages = {2559--2572},
number = {9},
month = sep,
abstract = {The staphylococcal accessory regulator (sarA) plays a central role
in the regulation of virulence in Staphylococcus aureus. To date,
studies involving sarA have focused on its activity as a global regulator
that modulates transcription of a wide variety of genes (>100) and
its role in virulence. However, there is also evidence to suggest
the existence of accessory elements that modulate SarA production
and/or function. A reporter system was developed to identify such
elements, and a new gene, msa (SA1233), mutation of which results
in reduced expression of SarA, was identified and characterized.
Additionally, it was shown that mutation of msa resulted in altered
transcription of the accessory gene regulator (agr) and the genes
encoding several virulence factors including alpha toxin (hla) and
protein A (spa). However, the impact of mutating msa was different
in the laboratory strain RN6390 and the clinical isolate UAMS-1.
For instance, mutation of msa caused a decrease in spa and hla transcription
in RN6390 but had a different effect in UAMS-1. The strain-dependent
effects of the msa mutation were similar to those observed previously,
which suggests that msa may modulate the production of specific virulence
factors through its impact on sarA. Interestingly, sequence analysis
of Msa suggests that it is a putative membrane protein with three
membrane-spanning regions, indicating that Msa might interact with
the environment. The findings show that msa is involved in the expression
of SarA and several virulence factors.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/152/9/2559}
}
@ARTICLE{Sampath2011,
author = {Sampath, Harini and Batra, Ayesha K. and Vartanian, Vladimir and
Carmical, J. Russ and Prusak, Deborah and King, Irena B. and Lowell,
Brian and Earley, Lauriel F. and Wood, Thomas G. and Marks, Daniel
L. and McCullough, Amanda K. and R. Stephen, Lloyd},
title = {Variable penetrance of metabolic phenotypes and development of high-fat
diet-induced adiposity in NEIL1-deficient mice},
journal = {Am J Physiol Endocrinol Metab},
year = {2011},
volume = {300},
pages = {E724--734},
number = {4},
month = apr,
abstract = {Exposure to chronic and acute oxidative stress is correlated with
many human diseases, including, but not limited to, cancer, heart
disease, diabetes, and obesity. In addition to cellular lipids and
proteins, cellular oxidative stress can result in damage to DNA bases,
especially in mitochondrial DNA. We previously described the development
of spontaneous late-onset obesity, hepatic steatosis, hyperinsulinemia,
and hyperleptinemia in mice that are deficient in the DNA glycosylase
nei-like 1 (NEIL1), which initiates base excision repair of several
oxidatively damaged bases. In the current study, we report that exposure
to a chronic oxidative stress in the form of a high-fat diet greatly
accelerates the development of obesity in neil1-/- mice. Following
a 5-wk high-fat diet challenge, neil1-/- mice gained significantly
more body weight than neil1+/+ littermates and had increased body
fat accumulation and moderate to severe hepatic steatosis. Analysis
of oxygen consumption by indirect calorimetry indicated a modest
reduction in total oxygen consumption in neil1-/- mice that was abolished
upon correction for lean body mass. Additionally, hepatic expression
of several inflammatory genes was significantly upregulated in neil1-/-
mice following high-fat diet challenge compared with chow-fed or
neil1+/+ counterparts. A long-term high-fat diet also induced glucose
intolerance as well as a significant reduction in mitochondrial DNA
and protein content in neil1-/- mice. Collectively, these data indicate
that NEIL1 deficiency results in an increased susceptibility to obesity
and related complications potentially by lowering the threshold for
tolerance of cellular oxidative stress in neil1-/- mice.},
comment = {10.1152/ajpendo.00387.2010},
url = {http://ajpendo.physiology.org/cgi/content/abstract/300/4/E724}
}
@ARTICLE{Sampath2011a,
author = {Sampath, Prabha and Lee, Qian Yi and Tanavde, Vivek},
title = {Identifying Translationally Regulated Genes During Stem Cell Differentiation},
journal = {Current Protocols in Stem Cell Biology},
year = {2011},
abstract = {This unit describes a protocol for genome-wide identification of translationally
regulated genes during embryonic stem cell differentiation using
integrated transcriptome and translation state profiling. Actively
translated mRNAs associated with multiple ribosomes (known as polysomes)
and translationally inactive mRNAs sequestered in messenger ribonucleoprotein
particles (mRNPs), can be separated by sucrose gradient fractionation
based on size. Because the number of ribosomes on a transcript correlates
with the rate of synthesis of its encoded protein, this allows an
operational distinction between well-translated and poorly translated
mRNA molecules. In this analysis, fractionated mRNA and total RNA
are used to probe microarrays to identify differentially translated
genes. Curr. Protoc. Stem Cell Biol. 18:1B.8.1-1B.8.13. © 2011 by
John Wiley & Sons, Inc.},
booktitle = {Current Protocols in Stem Cell Biology},
doi = {10.1002/9780470151808.sc01b08s18},
isbn = {9780470151808},
keywords = {embryonic stem cells, translational control, polysome analysis},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/9780470151808.sc01b08s18}
}
@ARTICLE{Sampath2008,
author = {Sampath, Prabha and Pritchard, David K. and Pabon, Lil and Reinecke,
Hans and Schwartz, Stephen M. and Morris, David R. and Murry, Charles
E.},
title = {A Hierarchical Network Controls Protein Translation during Murine
Embryonic Stem Cell Self-Renewal and Differentiation},
journal = {Cell Stem Cell},
year = {2008},
volume = {2},
pages = {448--460},
number = {5},
month = may,
abstract = {Summary Stem cell differentiation involves changes in transcription,
but little is known about translational control during differentiation.
We comprehensively profiled gene expression during differentiation
of murine embryonic stem cells (ESCs) into embryoid bodies by integrating
transcriptome analysis with global assessment of ribosome loading.
While protein synthesis was parsimonious during self-renewal, differentiation
induced an anabolic switch, with global increases in transcript abundance,
polysome content, protein synthesis, and protein content. Furthermore,
78% of transcripts showed increased ribosome loading, thereby enhancing
translational efficiency. Transcripts under exclusive translational
control included the transcription factor ATF5, the tumor suppressor
DCC, and the [beta]-catenin agonist Wnt1. We show that a hierarchy
of translational regulators, including mTOR, 4EBP1, and the RNA-binding
proteins DAZL and GRSF1, control global and selective protein synthesis
during ESC differentiation. Parsimonious translation in pluripotent
state and hierarchical translational regulation during differentiation
may be important quality controls for self-renewal and choice of
fate in ESCs.},
issn = {1934-5909},
keywords = {STEMCELL},
url = {http://www.sciencedirect.com/science/article/B8G3V-4SFRC98-D/2/60bedbfcaa37c3c059d190a53db31afa}
}
@ARTICLE{Sampey2011,
author = {Sampey, Brante P. and Vanhoose, Amanda M. and Winfield, Helena M.
and Freemerman, Alex J. and Muehlbauer, Michael J. and Fueger, Patrick
T. and Newgard, Christopher B. and Makowski, Liza},
title = {Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With
Liver and Adipose Inflammation: Comparison to High-Fat Diet},
journal = {Obesity},
year = {2011},
volume = {19},
pages = {1109--1117},
number = {6},
month = jun,
issn = {1930-7381},
publisher = {The Obesity Society},
url = {http://dx.doi.org/10.1038/oby.2011.18}
}
@ARTICLE{Sampson2011,
author = {Sampson, H Wayne and Chaput, Christopher D and Brannen, Jason and
Probe, Robert A and Guleria, Rakeshwar S and Pan, Jing and Baker,
Kenneth M and VanBuren, Vincent},
title = {Alcohol induced epigenetic perturbations during the inflammatory
stage of fracture healing},
journal = {Exp Biol Med},
year = {2011},
volume = {236},
pages = {1389-1401},
number = {12},
abstract = {It is well recognized by orthopedic surgeons that fractures of alcoholics
are more difficult to heal successfully and have a higher incidence
of non-union, but the mechanism of alcohol's effect on fracture healing
is unknown. In order to give direction for the study of the effects
of alcohol on fracture healing, we propose to identify gene expression
and microRNA changes during the early stages of fracture healing
that might be attributable to alcohol consumption. As the inflammatory
stage appears to be the most critical for successful fracture healing,
this paper focuses on the events at day three following fracture
or the stage of inflammation. Sprague-Dawley rats were placed on
an ethanol-containing or pair-fed Lieber and DeCarli diet for four
weeks prior to surgical fracture. Following insertion of a medullary
pin, a closed mid-diaphyseal fracture was induced using a Bonnarens
and Einhorn fracture device. At three days' post-fracture, the region
of the fracture calluses was harvested from the right hind-limb.
RNA was extracted and microarray analysis was conducted against the
entire rat genome. There were 35 genes that demonstrated significant
increased expression due to alcohol consumption and 20 that decreased
due to alcohol. In addition, the expression of 20 microRNAs was increased
and six decreased. In summary, while it is recognized that mRNA levels
may or may not represent protein levels successfully produced by
the cell, these studies reveal changes in gene expression that support
the hypothesis that alcohol consumption affects events involved with
inflammation. MicroRNAs are known to modulate mRNA and these findings
were consistent with much of what was seen with mRNA microarray analysis,
especially the involvement of smad4 which was demonstrated by mRNA
microarray, microRNA and polymerase chain reaction.},
doi = {10.1258/ebm.2011.011207},
eprint = {http://ebm.rsmjournals.com/cgi/reprint/236/12/1389.pdf},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/236/12/1389}
}
@ARTICLE{Sampson2007,
author = {Sampson, Valerie B. and Rong, Nancy H. and Han, Jian and Yang, Qunying
and Aris, Virginie and Soteropoulos, Patricia and Petrelli, Nicholas
J. and Dunn, Stephen P. and Krueger, Leslie J.},
title = {MicroRNA Let-7a Down-regulates MYC and Reverts MYC-Induced Growth
in Burkitt Lymphoma Cells},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {9762--9770},
number = {20},
month = oct,
abstract = {Regulation of the MYC oncogene remains unclear. Using 10058-F4, a
compound that inhibits MYC-MAX transcription factor, MYC protein
and gene expression were down-regulated in Namalwa cells, a Burkitt
lymphoma. Compound 10058-F4 decreased MYC mRNA (45%), MYC protein
(50%), and cell growth (32%). MYC-MAX transcription factor was disrupted
24 h after treatment, resulting in transcriptional inhibition of
target genes. Because microRNAs (miRNA) disrupt mRNA translation,
let-7a, let-7b, and mir-98 were selected using bioinformatics for
targeting MYC. Inhibition of MYC-MAX transcription factor with 10058-F4
increased levels of members of the let-7 family. In inhibited cells
at 24 h, let-7a, let-7b, and mir-98 were induced 4.9-, 1.3-, and
2.4-fold, respectively, whereas mir-17-5p decreased 0.23-fold. These
results were duplicated using microRNA multianalyte suspension array
technology. Regulation of MYC mRNA by let-7a was confirmed by transfections
with pre-let-7a. Overexpression of let-7a (190%) decreased Myc mRNA
(70%) and protein (75%). Down-regulation of Myc protein and mRNA
using siRNA MYC also elevated let-7a miRNA and decreased Myc gene
expression. Inverse coordinate regulation of let-7a and mir-17-5p
versus Myc mRNA by 10058-F4, pre-let-7a, or siRNA MYC suggested that
both miRNAs are Myc-regulated. This supports previous results in
lung and colon cancer where decreased levels of the let-7 family
resulted in increased tumorigenicity. Here, pre-let-7a transfections
led to down-regulation of expression of MYC and its target genes
and antiproliferation in lymphoma cells. These findings with let-7a
add to the complexity of MYC regulation and suggest that dysregulation
of these miRNAs participates in the genesis and maintenance of the
lymphoma phenotype in Burkitt lymphoma cells and other MYC-dysregulated
cancers. [Cancer Res 2007;67(20):9762-70]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/20/9762}
}
@ARTICLE{Samuel2005,
author = {Samuel, Marcus A. and Hall, Hardy and Krzymowska, Magdalena and Drzewiecka,
Kinga and Hennig, Jacek and Ellis, Brian E.},
title = {SIPK signaling controls multiple components of harpin-induced cell
death in tobacco},
journal = {The Plant Journal},
year = {2005},
volume = {42},
pages = {406--416},
number = {3},
abstract = {Summary Harpin from Pseudomonas syringae pv. phaseolicola (HrpZ) elicits
a rapid cell death response in tobacco plants. Multiple signaling
components, including mitogen-activated protein kinase (MAPK), reactive
oxygen species (ROS) and salicylic acid (SA), have been reported
to be involved in this cell death process, but the interaction between
these molecules is poorly understood. Here we show through utilizing
plants manipulated in SIPK expression levels that lack of SIPK results
in increased sensitivity to harpin with concomitant accumulation
of higher levels of ROS. Conversely, SIPK-overexpressing plants show
reduced sensitivity to harpin relative to wild-type plants, and display
reduced ROS accumulation. Harpin-induced cell death was found to
be conditional on the ability of the plant to accumulate SA, whereas
harpin induction of MAPK activation and ROS accumulation are not.
However, harpin-induced ROS accumulation is required for activation
of SIPK and wound-induced protein kinase. Transcriptional profiling
revealed that suppression of SIPK signaling also affects early expression
of a range of pathogen- and stress-responsive genes during harpin
challenge.},
issn = {1365-313X},
keywords = {harpin, reactive oxygen species, SIPK, wound-induced protein kinase,
salicylic acid, cell death},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2005.02382.x}
}
@ARTICLE{Samuels2010,
author = {Samuels, Amy and Peeva, Violet and Papa, Rachael and Firth, Marin
and Francis, Richard and Beesley, Alex and Lock, Richard and Kees,
Ursula},
title = {Validation of a mouse xenograft model system for gene expression
analysis of human acute lymphoblastic leukaemia},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {256},
number = {1},
abstract = {BACKGROUND:Pre-clinical models that effectively recapitulate human
disease are critical for expanding our knowledge of cancer biology
and drug resistance mechanisms. For haematological malignancies,
the non-obese diabetic/severe combined immunodeficient (NOD/SCID)
mouse is one of the most successful models to study paediatric acute
lymphoblastic leukaemia (ALL). However, for this model to be effective
for studying engraftment and therapy responses at the whole genome
level, careful molecular characterisation is essential.RESULTS:Here,
we sought to validate species-specific gene expression profiling
in the high engraftment continuous ALL NOD/SCID xenograft. Using
the human Affymetrix whole transcript platform we analysed transcriptional
profiles from engrafted tissues without prior cell separation of
mouse cells and found it to return highly reproducible profiles in
xenografts from individual mice. The model was further tested with
experimental mixtures of human and mouse cells, demonstrating that
the presence of mouse cells does not significantly skew expression
profiles when xenografts contain 90% or more human cells. In addition,
we present a novel in silico and experimental masking approach to
identify probes and transcript clusters susceptible to cross-species
hybridisation.CONCLUSIONS:We demonstrate species-specific transcriptional
profiles can be obtained from xenografts when high levels of engraftment
are achieved or with the application of transcript cluster masks.
Importantly, this masking approach can be applied and adapted to
other xenograft models where human tissue infiltration is lower.
This model provides a powerful platform for identifying genes and
pathways associated with ALL disease progression and response to
therapy in vivo.},
doi = {10.1186/1471-2164-11-256},
issn = {1471-2164},
pubmedid = {20406497},
url = {http://www.biomedcentral.com/1471-2164/11/256}
}
@ARTICLE{Samulin2009,
author = {Samulin, Johanna and Berget, Ingunn and Grindflek, Eli and Lien,
Sigbjørn and Sundvold, Hilde},
title = {Changes in lipid metabolism associated gene transcripts during porcine
adipogenesis},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2009},
volume = {153},
pages = {8--17},
number = {1},
month = may,
abstract = {Pigs are recognised as suitable biomedical models to study obesity
and obesity-related diseases; however, little is known about adipose
tissue development and adipogenesis in pigs. In this study, the temporal
expression of key genes involved in lipid metabolism was investigated
during porcine adipogenesis and the metabolic fate of exogenously
administered palmitic acid (16:0) was examined in differentiating
preadipocytes. The expression of genes encoding elongases and desaturases
increased simultaneously with those involved in fatty acid and triacylglycerol
synthesis during porcine adipogenesis, and a high biosynthesis of
monounsaturated fatty acids was measured prior to storage in differentiating
preadipocytes. Although the total fatty acid oxidation in differentiating
preadipocytes was low, differentiating cells showed increased expression
of hormone-sensitive lipase and mitochondrial and peroxisomal genes.
These data provide new insight into the temporal expression of genes
involved in lipid metabolism during porcine adipogenesis and suggest
a possible role of elongation and desaturation events prior to lipid
accumulation in porcine adipocytes.},
issn = {1096-4959},
keywords = {Desaturation, Differentiation, Elongation, Fatty acid oxidation, Gene
expression, Lipid metabolism, Pig, Proliferation},
url = {http://www.sciencedirect.com/science/article/B6T2R-4VDH916-1/2/cddb50badf39427fb6e713172d2ada84}
}
@ARTICLE{Samulin2008,
author = {Samulin, Johanna and Berget, Ingunn and Lien, Sigbjørn and Sundvold,
Hilde},
title = {Differential gene expression of fatty acid binding proteins during
porcine adipogenesis},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2008},
volume = {151},
pages = {147--152},
number = {2},
month = oct,
abstract = {Four different subtypes of fatty acid binding proteins i.e. liver-type
FABP1, heart/muscle-type FABP3, adipocyte-type FABP4 and epithelial/epidermal-type
FABP5 are expressed in adipose tissue. However, only the regulatory
role of FABP4 in adipogenesis has been thoroughly investigated. To
increase the knowledge on possible roles of these FABP subtypes in
preadipocyte differentiation, gene expression patterns were examined
during adipogenesis in pig (Sus scrofa). FABP1 expression was induced
in proliferating cells, whereas FABP3, FABP4 and FABP5 expression
increased throughout preadipocyte differentiation. Interestingly,
the FABP4 and FABP5 expression increased early in the differentiation,
followed by FABP3 later in the differentiation process. This indicates
a role of FABP4 and FABP5 in intracellular fatty acid transport during
initiation of differentiation, whereas, FABP3 likely is involved
in the transport of fatty acids during intermediate stages of adipogenesis.
In this study we demonstrate that FABP3, FABP4 and FABP5 expression
is correlated with that of the peroxisome proliferator-activated
receptors alpha and gamma (PPARA and PPARG). Altogether, this suggests
a role of FABP1 during cell proliferation, whereas a coordinated
expression of FABP3, FABP4 and FABP5 together with that of PPARA,
PPARG1 and PPARG2 might be critical for the metabolic regulation
during porcine adipogenesis.},
issn = {1096-4959},
keywords = {Adipogenesis, Differentiation, Fatty acid binding proteins, Gene expression,
Peroxisome proliferator-activated receptors, Pig, Proliferation,
Stromal-vascular cells},
url = {http://www.sciencedirect.com/science/article/B6T2R-4STGRY2-2/2/61c700a7d7abf0a8839d0a104134fc94}
}
@ARTICLE{Samulin2008a,
author = {Samulin, Johanna and Lien, Sigbjørn and Grindflek, Eli and Berget,
Ingunn and Ruyter, Bente and Sundvold, Hilde},
title = {Depot specific differences during adipogenesis of porcine stromal-vascular
cells},
journal = {Cell Biology International},
year = {2008},
volume = {32},
pages = {525--531},
number = {5},
month = may,
abstract = {Recently a role of adipose tissue as an endocrine organ secreting
factors involved in the regulation of whole-body energy homeostasis
has emerged. Preadipocytes in different fat depots have distinct
adipogenic potential and the metabolic activity differs between mature
adipocytes of different depot origins. Here we describe the proliferation
and differentiation of stromal-vascular cells derived from subcutaneous
and visceral fat depots of adult pigs. We demonstrate that subcutaneous
porcine preadipocytes proliferate more actively and that individual
subcutaneous adipocytes have a more rapid accumulation of triacylglycerols
than visceral cells. During differentiation, subcutaneous and visceral
preadipocytes showed similar gene expression patterns with increased
expression of adiponectin (APM1), adipocyte-specific fatty acid binding
protein (FABP4), catalase (CAT), and peroxisome proliferator-activated
receptor gamma 2 (PPARG2). Furthermore, initial data showing depot-originated
effects on the expression of CAT, carnitine palmitoyl transferase
1B (CPT1B) and FABP4 suggest possible depot specific differences
in the function and metabolism of mature porcine adipocytes.},
issn = {1065-6995},
keywords = {Adipocyte differentiation, Porcine, Depot origin, Gene expression,
Subcutaneous, Visceral, Stromal-vascular cells},
url = {http://www.sciencedirect.com/science/article/B6WCB-4RNR6YP-5/2/1d58d714314182c3b429c948791ca581}
}
@ARTICLE{Sanchez2011,
author = {Sanchez, Brian C. and Carter, Barbara and Hammers, Heather R. and
Sepúlveda, MarÃa S},
title = {Transcriptional response of hepatic largemouth bass (Micropterus
salmoides) mRNA upon exposure to environmental contaminants},
journal = {Journal of Applied Toxicology},
year = {2011},
volume = {31},
pages = {108--116},
number = {2},
abstract = {Abstract Microarrays enable gene transcript expression changes in
near-whole genomes to be assessed in response to environmental stimuli.
We utilized oligonucleotide microarrays and subsequent gene set enrichment
analysis (GSEA) to assess patterns of gene expression changes in
male largemouth bass (Micropterus salmoides) hepatic tissues after
a 96 h exposure to common environmental contaminants. Fish were
exposed to atrazine, cadmium chloride, PCB 126, phenanthrene and
toxaphene via intraperitoneal injection with target body burdens
of 3.0, 0.00067, 2.5, 50 and 100 µg g−1, respectively. This
was conducted in an effort to identify potential biomarkers of exposure.
The expressions of 4, 126, 118, 137 and 58 mRNA transcripts were
significantly (P ≤ 0.001, fold change ≥2×) affected by exposure
to atrazine, cadmium chloride, PCB 126, phenanthrene and toxaphene
exposures, respectively. GSEA revealed that none, four, five, five
and three biological function gene ontology categories were significantly
influenced by exposure to these chemicals, respectively. We observed
that cadmium chloride elicited ethanol metabolism responses, and
along with PCB 126 and phenanthrene affected transcripts associated
with protein biosynthesis. PCB 126, phenanthrene and toxaphene also
influenced one-carbon compound metabolism while PCB 126 and phenanthrene
affected mRNA transcription and mRNA export from the nucleus and
may have induced an antiestrogenic response. Atrazine was found to
alter the expression of few hepatic transcripts. This work has highlighted
several biological processes of interest that may be helpful in the
development of gene transcript biomarkers of chemical exposure in
fish. Copyright © 2010 John Wiley & Sons, Ltd.},
doi = {10.1002/jat.1553},
issn = {1099-1263},
keywords = {toxicogenomics, toxaphene, phenanthrene, PCB 126, atrazine, cadmium,
fish, aquatic},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/jat.1553}
}
@ARTICLE{Sanchez2008,
author = {Sanchez, Diego H. and Lippold, Felix and Redestig, Henning and Hannah,
Matthew A. and Erban, Alexander and Krämer, Ute and Kopka, Joachim
and Udvardi, Michael K.},
title = {Integrative functional genomics of salt acclimatization in the model
legume Lotus japonicus},
journal = {The Plant Journal},
year = {2008},
volume = {53},
pages = {973--987},
number = {6},
abstract = {Summary The model legume Lotus japonicus was subjected to non-lethal
long-term salinity and profiled at the ionomic, transcriptomic and
metabolomic levels. Two experimental designs with various stress
doses were tested: a gradual step acclimatization and an initial
acclimatization approach. Ionomic profiling by inductively coupled
plasma/atomic emission spectrometry (ICP-AES) revealed salt stress-induced
reductions in potassium, phosphorus, sulphur, zinc and molybdenum.
Microarray profiling using the Lotus Genechip® allowed the identification
of 912 probesets that were differentially expressed under the acclimatization
regimes. Gas chromatography/mass spectrometry-based metabolite profiling
identified 147 differentially accumulated soluble metabolites, indicating
a change in metabolic phenotype upon salt acclimatization. Metabolic
changes were characterized by a general increase in the steady-state
levels of many amino acids, sugars and polyols, with a concurrent
decrease in most organic acids. Transcript and metabolite changes
exhibited a stress dose-dependent response within the range of NaCl
concentrations used, although threshold and plateau behaviours were
also observed. The combined observations suggest a successive and
increasingly global requirement for the reprogramming of gene expression
and metabolic pathways to maintain ionic and osmotic homeostasis.
A simple qualitative model is proposed to explain the systems behaviour
of plants during salt acclimatization.},
issn = {1365-313X},
keywords = {acclimatization, ionomic, Lotus, metabolomic, salt stress, transcriptomic},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2007.03381.x}
}
@ARTICLE{Sanchez2010,
author = {Sanchez, R.L. and Reddy, A.P. and Bethea, C.L.},
title = {Ovarian steroid regulation of the midbrain corticotropin releasing
factor and urocortin systems in macaques},
journal = {Neuroscience},
year = {2010},
volume = {171},
pages = {893--909},
number = {3},
month = dec,
abstract = {A significant number of postmenopausal women report increased anxiety
and vulnerability to stress, which has been linked to decreased secretion
of ovarian steroids. Communication between the serotonin system and
the corticotropin releasing factor (CRF) system determines stress
sensitivity or resilience. This study examines the effects of the
ovarian steroids, estradiol (E) and progesterone (P) on the CRF system
components that impact serotonin neurons in the midbrain of nonhuman
primates. Ovariectomized rhesus macaques were treated with placebo,
E alone for 1 month, or E supplemented with P for the last 2 weeks.
Quantitative (q)RT-PCR and immunocytochemistry were employed. E±P
treatment decreased CRF-R1 and increased CRF-R2 gene expression in
hemi-midbrain blocks and in laser captured serotonin neurons. Also
in hemi-midbrains, E treatment increased urocortin 1 (UCN1) and CRFBP
gene expression, but supplemental P treatment reversed these effects.
E±P decreased CRF fiber density in the dorsal, interfascicular and
median raphe nuclei and decreased CRF-R1 immunostaining in the dorsal
raphe. E increased CRF-R2 immunostaining in the dorsal and median
raphe. E±P increased UCN1 immunostaining in the cell bodies and increased
UCN1 fiber density in the caudal linear nucleus. Estrogen receptor
beta (ER[beta]), but not ER[alpha] was detected in the nucleus of
UCN1-positive neurons. While the mechanism of ovarian hormone regulation
of the midbrain CRF system requires further investigation, these
studies clearly demonstrate another pathway by which ovarian hormones
may have positive effects on anxiety and mood regulation.},
issn = {0306-4522},
keywords = {serotonin, corticotropin, urocortin, estrogen, progesterone, macaques},
url = {http://www.sciencedirect.com/science/article/pii/S0306452210012091}
}
@ARTICLE{Sanchez-Abarca2010,
author = {Sanchez-Abarca, Luis I. and Gutierrez-Cosio, Silvia and Santamaria,
Carlos and Caballero-Velazquez, Teresa and Blanco, Belen and Herrero-Sanchez,
Carmen and Garcia, Juan L. and Carrancio, Soraya and Hernandez-Campo,
Pilar and Gonzalez, Francisco J. and Flores, Teresa and Ciudad, Laura
and Ballestar, Esteban and del Canizo, Consuelo and San Miguel, Jesus
F. and Perez-Simon, Jose A.},
title = {Immunomodulatory effect of 5-azacytidine (5-azaC): potential role
in the transplantation setting},
journal = {Blood},
year = {2010},
volume = {115},
pages = {107--121},
number = {1},
month = jan,
abstract = {Cytokine genes are targets of multiple epigenetic mechanisms in T
lymphocytes. 5-azacytidine (5-azaC) is a nucleoside-based DNA methyltransferase
inhibitor that induces demethylation and gene reactivation. In the
current study, we analyzed the effect of 5-azaC in T-cell function
and observed that 5-azaC inhibits T-cell proliferation and activation,
blocking cell cycle in the G0 to G1 phase and decreasing the production
of proinflammatory cytokines such as tumor necrosis factor-{alpha}
and interferon-{gamma}. This effect was not attributable to a proapoptotic
effect of the drug but to the down-regulation of genes involved in
T-cell cycle progression and activation such as CCNG2, MTCP1, CD58,
and ADK and up-regulation of genes that induce cell-growth arrest,
such as DCUN1D2, U2AF2, GADD45B, or p53. A longer exposure to the
drug leads to demethylation of FOXP3 promoter, overexpression of
FOXP3, and expansion of regulatory T cells. Finally, the administration
of 5-azaC after transplantation prevented the development of graft-versus-host
disease, leading to a significant increase in survival in a fully
mismatched bone marrow transplantation mouse model. In conclusion,
the current study shows the effect of 5-azaC in T lymphocytes and
illustrates its role in the allogeneic transplantation setting as
an immunomodulatory drug, describing new pathways that must be explored
to prevent graft-versus-host disease.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/1/107}
}
@ARTICLE{Sanchez-Arago2010,
author = {Sanchez-Arago, Maria and Chamorro, Margarita and Cuezva, Jose M.},
title = {Selection of cancer cells with repressed mitochondria triggers colon
cancer progression},
journal = {Carcinogenesis},
year = {2010},
volume = {31},
pages = {567--576},
number = {4},
month = apr,
abstract = {The contribution that mitochondrial bioenergetics could have in cancer
development is debated. Here, we have generated HCT116-derived colocarcinoma
cell lines expressing different levels of the {beta} catalytic subunit
of the mitochondrial H+-adenosine triphosphate synthase to assess
the contribution of mitochondrial bioenergetics in colon cancer progression.
The generated cells exhibit large ultrastructural, transcriptomic,
proteomic and functional differences in their mitochondria and in
their in vivo tumor forming capacity. We show that the activity of
oxidative phosphorylation defines the rate of glucose utilization
by aerobic glycolysis. The aggressive cellular phenotype, which is
highly glycolytic, is bound to the deregulated expression of genes
involved in metabolic processes, the regulation of the cell cycle,
apoptosis, angiogenesis and cell adhesion. Remarkably, the molecular
and ultrastructural analysis of the tumors derived from the three
HCT116 cell lines under study highlight that tumor promotion inevitably
requires the selection of cancer cells with a repressed biogenesis
and functional activity of mitochondria, i.e. the highly glycolytic
phenotype is selected for tumor development. The tumor forming potential
of the cells is a non-genetically acquired condition that provides
the cancer cell with a cell-death resistant phenotype. An abrogated
mitochondrial respiration contributes to a diminished potential for
reactive oxygen species signaling in response to 5-fluorouracil treatment.
Treatment of cancer cells with dichloroacetate partially restores
the functional differentiation of mitochondria and promotes tumor
regression, emphasizing the reversible nature of the metabolic trait
of cancer.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/31/4/567}
}
@ARTICLE{Sanchez-Barbero2005,
author = {Sanchez-Barbero, Fernando and Strassner, Jochen and Garcia-Canero,
Rafael and Steinhilber, Wolfram and Casals, Cristina},
title = {Role of the Degree of Oligomerization in the Structure and Function
of Human Surfactant Protein A},
journal = {J. Biol. Chem.},
year = {2005},
volume = {280},
pages = {7659--7670},
number = {9},
month = mar,
abstract = {The role of the degree of oligomerization in the structure and function
of human surfactant protein A (SP-A) was investigated using a human
SP-A1 mutant (SP-A1{Delta}AVC,C6S), expressed in mammalian cells,
resulting from site-directed substitution of serine for Cys6 and
substitution of a functional signal peptide for the cysteine-containing
SP-A signal sequence. This Cys6 mutant lacked the NH2-terminal Ala-3-Val-2-Cys-1
({Delta}AVC) extension present in some SP-A1 isoforms. SP-A1{Delta}AVC,C6S
was assembled exclusively as trimers as detected by electron microscopy
and size exclusion chromatography. Trimeric SP-A1{Delta}AVC,C6S was
compared with supratrimeric SP-A1, which is structurally and functionally
comparable to the octadecameric protein isolated from human lung
lavages. SP-A1{Delta}AVC,C6S showed reduced thermal stability of
the collagen domain, studied by circular dichroism, and increased
susceptibility to trypsin degradation. The Tm was 32.7 {degrees}C
for SP-A1{Delta}AVC,C6S and 44.5 {degrees}C for SP-A1. Although SP-A1{Delta}AVC,C6S
was capable of binding to calcium, rough lipopolysaccharide, and
phospholipid vesicles, this mutant was unable to induce rough lipopolysaccharide
and phospholipid vesicle aggregation, to enhance the interfacial
adsorption of SP-B/SP-C-surfactant membranes, and to undergo self-association
in the presence of Ca2+. On the other hand, the lack of supratrimeric
assembly hardly affected the ability of SP-A1{Delta}AVC,C6S to inhibit
the production of tumor necrosis factor-{alpha} by macrophage-like
U937 cells stimulated with either smooth or rough lipopolysaccharide.
We conclude that supratrimeric assembly of human SP-A is essential
for collagen triple helix stability at physiological temperatures,
protection against proteases, protein self-association, and SP-A-induced
ligand aggregation. The supratrimeric assembly is not essential for
the binding of SP-A to ligands and anti-inflammatory effects of SP-A.},
url = {http://www.jbc.org/cgi/content/abstract/280/9/7659}
}
@ARTICLE{Sanchez-Carbayo2003,
author = {Sanchez-Carbayo, Marta and Saint, Fabien and Lozano, Juan Jose and
Viale, Agnes and Cordon-Cardo, Carlos},
title = {Comparison of Gene Expression Profiles in Laser-Microdissected, Nonembedded,
and OCT-Embedded Tumor Samples by Oligonucleotide Microarray Analysis},
journal = {Clin. Chem.},
year = {2003},
volume = {49},
pages = {2096--2100},
number = {12},
month = dec,
url = {http://www.clinchem.org/cgi/content/full/49/12/2096}
}
@ARTICLE{Sanchez-Carbayo2007,
author = {Sanchez-Carbayo, Marta and Socci, Nicholas D. and Kirchoff, Thomas
and Erill, Nadina and Offit, Keneth and Bochner, Bernard H. and Cordon-Cardo,
Carlos},
title = {A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial
Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {3215--3220},
number = {11},
month = jun,
abstract = {Purpose: The HDM2 gene represents one of the central nodes in the
p53 pathway. A recent study reported the association of a single
nucleotide polymorphism (SNP309) in the HDM2 promoter region with
accelerated tumor formation in both hereditary and sporadic cancers.
In this study, we aim to evaluate the SNP309 in bladder cancer and
to link it to TP53 status. Experimental Design: SNP309 genotyping
and TP53 mutation status were done on 141 bladder tumors and 8 bladder
cancer cell lines using a RFLP strategy and TP53 genotyping arrays,
respectively. Transcript profiling of a subset of cases (n = 41)
was done using oligonucleotide arrays to identify genes differentially
expressed regarding their SNP309 status. Results: Of 141 bladder
tumors analyzed, 36.9% displayed the SNP309 wild-type (WT; T/T) genotype,
whereas 11.3% were homozygous (G/G) and 51.8% were heterozygous (T/G)
cases. Patients with superficial disease and the G/G genotype had
an earlier age on onset than those with the T/G or T/T genotypes
(P = 0.029). Tumors with SNP309 WT genotype significantly displayed
TP53 mutations when compared with tumors harboring G/G or T/G genotypes
(P < 0.05). SNP309 WT cases had a poorer overall survival than cases
with G/G and T/G genotypes (P < 0.05). TP53 mutation status provided
enhanced prognostic value (P < 0.001). Transcript profiling identified
TP53 targets among those differentially expressed between tumors
displaying G/G or T/G SNP309 versus WT cases. Conclusions: SNP309
is a frequent event in bladder cancer, related to earlier onset of
superficial disease and TP53 mutation status. SNP309 genotypes were
found to be associated with clinical outcome.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/11/3215}
}
@ARTICLE{Sanchez-Carbayo2006,
author = {Sanchez-Carbayo, Marta and Socci, Nicholas D. and Lozano, Juanjo
and Saint, Fabien and Cordon-Cardo, Carlos},
title = {Defining Molecular Profiles of Poor Outcome in Patients With Invasive
Bladder Cancer Using Oligonucleotide Microarrays},
journal = {J. Clin. Oncol.},
year = {2006},
volume = {24},
pages = {778--789},
number = {5},
month = feb,
abstract = {PURPOSE: Bladder cancer is a common malignancy characterized by a
poor clinical outcome when tumors progress into invasive disease.
We sought to define genetic signatures characteristic of aggressive
clinical behavior in advanced bladder tumors. METHODS: Oligonucleotide
arrays were utilized to analyze the transcript profiles of 105 bladder
tumors: 33 superficial, 72 invasive lesions, and 52 normal urothelium.
Hierarchical clustering and supervised algorithms were used to classify
and stratify bladder tumors on the basis of stage, node metastases,
and overall survival. Immunohistochemical analyses on bladder cancer
tissue arrays (n = 294 cases) served to validate associations between
marker expression, staging and outcome. RESULTS: Hierarchical clustering
classified normal urothelium, superficial, and invasive tumors with
82.2% accuracy, and stratified bladder tumors on the basis of clinical
outcome. Predictive algorithms rendered an 89%-correct rate for tumor
staging using genes differentially expressed between superficial
and invasive tumors. Accuracies of 82% and 90% were obtained for
predicting overall survival when considering all patients with bladder
cancer or only patients with invasive disease, respectively. A genetic
profile consisting of 174 probes was identified in those patients
with positive lymph nodes and poor survival. Two independent Global
Test runs confirmed the robust association of this profile with lymph
node metastases (P = 7.3-13) and overall survival (P = 1.9-14) simultaneously.
Immunohistochemical analyses on tissue arrays sustained the significant
association of synuclein with tumor staging and clinical outcome
(P = .002). CONCLUSION: Gene profiling provides a genomic-based classification
scheme of diagnostic and prognostic utility for stratifying advanced
bladder cancer. Identification of this poor outcome profile could
assist in selecting patients who may benefit from more aggressive
therapeutic intervention.},
url = {http://jco.ascopubs.org/cgi/content/abstract/24/5/778}
}
@ARTICLE{Sanchez-Carbayo2006a,
author = {Sanchez-Carbayo, Marta and Socci, Nicholas D. and Lozano, Juan Jose
and Haab, Brian B. and Cordon-Cardo, Carlos},
title = {Profiling Bladder Cancer Using Targeted Antibody Arrays},
journal = {Am. J. Pathol.},
year = {2006},
volume = {168},
pages = {93--103},
number = {1},
month = jan,
abstract = {Bladder cancer is a common malignancy requiring a high degree of surveillance
because of the frequent recurrences and the poor clinical outcome
of invasive disease. To date, serum biomarkers for bladder cancer
lack optimal sensitivity and specificity to assist in diagnosis and
disease categorization. Here, we designed antibody arrays for bladder
cancer by selecting antibodies against targets differentially expressed
in bladder tumors. Serum protein profiles measured by an antibody
array containing 254 antibodies discriminated bladder cancer patients
from controls (n = 95) with a correct classification rate of 93.7%.
A second independent antibody array containing 144 antibodies revealed
that protein profiles provide predictive information by stratifying
patients with bladder tumors (n = 37) based on their overall survival
(P = 0.0479). In addition, serum proteins, such as c-met, that were
top ranked at identifying bladder cancer patients were associated
with pathological stage, tumor grade, and survival when validated
by immunohistochemistry of tissue microarrays containing bladder
tumors (n = 173). This study provides experimental evidence for the
use of several integrated technologies strengthening the process
of biomarker discovery. Serum protein profiles obtained by antibody
arrays represent comprehen-sive means for bladder cancer diagnosis
and clinical outcome stratification, which could potentially assist
in selection of cancer patients who would benefit from early, individualized
therapeutic intervention.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/168/1/93}
}
@ARTICLE{Sanchez-Carbayo2007a,
author = {Sanchez-Carbayo, Marta and Socci, Nicholas D. and Richstone, Lee
and Corton, Marta and Behrendt, Nille and Wulkfuhle, Julia and Bochner,
Bernard and Petricoin, Emmanuel and Cordon-Cardo, Carlos},
title = {Genomic and Proteomic Profiles Reveal the Association of Gelsolin
to TP53 Status and Bladder Cancer Progression},
journal = {Am. J. Pathol.},
year = {2007},
volume = {171},
pages = {1650--1658},
number = {5},
month = nov,
abstract = {Bladder cancer transformation and immortalization require the inactivation
of key regulatory genes, including TP53. Genotyping of a large cohort
of bladder cancer patients (n = 256) using the TP53 GeneChip showed
mutations in 103 cases (40.2%), the majority of them mapping to the
DNA-binding core domain. TP53 mutation status was significantly associated
with tumor stage (P = 0.0001) and overall survival for patients with
advanced disease (P = 0.01). Transcript profiling using oligonucleotide
arrays was performed on a subset of these cases (n = 46). Supervised
analyses identified genes differentially expressed between invasive
bladder tumors with wild-type (n = 24) and mutated TP53 (n = 22).
Pathway analyses of top-ranked genes supported the central role of
TP53 in the functional network of such gene patterns. A proteomic
strategy using reverse phase arrays with protein extracts of bladder
cancer cell lines validated the association of identified differentially
expressed genes, such as gelsolin, to TP53 status. Immunohistochemistry
on tissue microarrays (n = 294) revealed that gelsolin was associated
with tumor stage and overall survival, correlating positively with
TP53 status in a subset of these patients. This study further reveals
that TP53 mutations are frequent events in bladder cancer progression
and identified gelsolin related to TP53 status, tumor staging, and
clinical outcome by independent high-throughput strategies.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/171/5/1650}
}
@ARTICLE{Sanchez-Gurmaches2011,
author = {Sanchez-Gurmaches, Joan and Ostbye, Tone-Kari and Navarro, Isabel
and Torgersen, Jacob and Hevroy, Ernst Morten and Ruyter, Bente and
Torstensen, Bente E.},
title = {In vivo and in vitro insulin and fasting control of the transmembrane
fatty acid transport proteins in Atlantic salmon (Salmo salar)},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {301},
pages = {R947-957},
number = {4},
abstract = {We have examined the nutritional and insulin regulation of the mRNA
expression of transmembrane fatty acid (FA) transporters [FA transport
protein-1 (FATP1) and CD36] together with the lipoprotein lipase
(LPL), the cytosolic FA carrier FA binding protein (FABP3), and mitochondrial
FA-CoA and -carnitine palmitoyl transferase carriers (CPT)1 and -2
in Atlantic salmon tissues and myocyte cell culture. Two weeks of
fasting diminished FATP1, CD36, and LPL in adipose tissue, suggesting
a reduction in FA uptake, while FABP3 increased in liver, probably
enhancing the transport of FA to the mitochondria. Insulin injection
decreased FATP1 and CD36 in white and red muscles, while both transporters
were upregulated in the adipose tissue in agreement with the role
of insulin-inhibiting muscle FA oxidation and stimulating adipose
fat stores. Serum deprivation of 48 h in Atlantic salmon myotubes
increased FATP1, FABP3, and CPT-2, while CPT-1 was diminished. In
myotubes, insulin induced FATP1 expression but decreased CD36, FABP3,
and LPL, suggesting that FATP1 could be more involved in the insulin-stimulated
FA uptake. Insulin increased the FA uptake in myotubes mediated,
at least in part, through the relocation of FATP1 protein to the
plasma membrane. Overall, Atlantic salmon FA transporters are regulated
by fasting and insulin on in vivo and in vitro models.},
doi = {10.1152/ajpregu.00289.2011},
eprint = {http://ajpregu.physiology.org/cgi/reprint/301/4/R947.pdf},
url = {http://ajpregu.physiology.org/cgi/content/abstract/301/4/R947}
}
@ARTICLE{Sanchez-Pons2011,
author = {Sanchez-Pons, Nuria and Irar, Sami and Garcia-Muniz, Nora and Vicient,
Carlos},
title = {Transcriptomic and proteomic profiling of maize embryos exposed to
camptothecin},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {91},
number = {1},
abstract = {BACKGROUND:Camptothecin is a plant alkaloid that specifically binds
topoisomerase I, inhibiting its activity and inducing double stranded
breaks in DNA, activating the cell responses to DNA damage and, in
response to severe treatments, triggering cell death. RESULTS:Comparative
transcriptomic and proteomic analyses of maize embryos that had been
exposed to camptothecin were conducted. Under the conditions used
in this study, camptothecin did not induce extensive degradation
in the genomic DNA but induced the transcription of genes involved
in DNA repair and repressed genes involved in cell division. Camptothecin
also affected the accumulation of several proteins involved in the
stress response and induced the activity of certain calcium-dependent
nucleases. We also detected changes in the expression and accumulation
of different genes and proteins involved in post-translational regulatory
processes.CONCLUSIONS:This study identified several genes and proteins
that participate in DNA damage responses in plants. Some of them
may be involved in general responses to stress, but others are candidate
genes for specific involvement in DNA repair. Our results open a
number of new avenues for researching and improving plant resistance
to DNA injury.},
doi = {10.1186/1471-2229-11-91},
issn = {1471-2229},
pubmedid = {21595924},
url = {http://www.biomedcentral.com/1471-2229/11/91}
}
@ARTICLE{Sanchez-Simon2010,
author = {Sanchez-Simon, Fatima Macho and Arenzana, Francisco J. and Rodriguez,
Raquel E.},
title = {In vivo effects of morphine on neuronal fate and opioid receptor
expression in zebrafish embryos},
journal = {European Journal of Neuroscience},
year = {2010},
volume = {32},
pages = {550--559},
number = {4},
abstract = {Abstract Morphine remains one of the most potent analgesic compounds
used to control chronic pain despite its known adverse effects. It
binds to the opioid receptors mu, delta and kappa, which are involved
in aspects of neuronal fate such as cell proliferation, neuroprotection
and neuronal differentiation. However, the effect of morphine on
these processes is controversial and in vitro studies, as well as
in vivo studies on adults and neonates in mammalian models, have
not been able to clarify the diverse roles of morphine in the central
nervous system. We have used zebrafish embryos to determine in vivo
how morphine affects neuronal fate and opioid receptor gene expression
and to elucidate if there is a link between these processes. Our
results show that at 24 and 48Â h post fertilization (hpf) morphine
enhances cell proliferation, although it has opposing effects as
an inducer of neuronal differentiation at these two stages, increasing
the number of certain neuronal populations at 24Â hpf and decreasing
it at 48Â hpf. The present study also demonstrates that in 24-hpf
embryos morphine acts as a neuroprotector against glutamate damage
in motor neurons and Pax-6-positive neurons. Furthermore, the gene
expression of the opioid receptors is altered by embryonic exposition
to morphine. In conclusion, our study sheds new light on the in vivo
roles of morphine, and it indicates for the first time that its implication
in cell proliferation and neuroprotection might be related to changes
in the gene expression of opioid receptors.},
issn = {1460-9568},
keywords = {cell proliferation, neuronal differentiation, neuroprotection, qPCR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2010.07317.x}
}
@ARTICLE{Sanchez-Vega2006,
author = {Sanchez-Vega, Beatriz and Krett, Nancy and Rosen, Steven T. and Gandhi,
Varsha},
title = {Glucocorticoid receptor transcriptional isoforms and resistance in
multiple myeloma cells},
journal = {Mol. Cancer Ther.},
year = {2006},
volume = {5},
pages = {3062--3070},
number = {12},
month = dec,
abstract = {Although glucocorticoids play an important role in the treatment of
multiple myeloma, some patients do not respond or develop resistance.
The glucocorticoid receptor (GR), a single gene, mediates the effects
of glucocorticoids. Using a model system of a multiple myeloma cell
line sensitive to glucocorticoids and its early and late resistant
variants, we have analyzed mutations in the GR gene, detected the
presence of different transcriptional isoforms, quantified their
levels of expression, and identified the promoters that regulate
their expression. Levels of GR transcripts were comparable with the
expression of total GR protein. Development of resistance correlates
with an overall reduction in GR mRNA levels. This decrease in GR
levels is neither due to mutation of the gene nor due to methylation.
GR{alpha} is the predominant isoform in the sensitive cell line decreasing
in expression in the early resistant cells and virtually undetectable
in late resistant cells. GR-P is expressed at equivalent levels in
both sensitive and early resistant cells, whereas in the late resistant
cells, GR-P is the predominant isoform. GR-A is only expressed in
the early resistant cell line. GR{beta} is the least expressed isoform
in all cell lines. Interestingly, the level of expression of exon
1-exon 2 RNA fragments remains similar in sensitive and resistant
cell lines. Resistant cells became sensitive to glucocorticoids after
GR{alpha} transfection. In conclusion, we show different patterns
of expression of the GR isoforms and provide evidence that a decline
in the expression of GR{alpha} may be associated with development
of resistance. [Mol Cancer Ther 2006;5(12):3062-70]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/5/12/3062}
}
@ARTICLE{Sancho-Bru2007,
author = {Sancho-Bru, Pau and Bataller, Ramón and Fernandez-Varo, Guillermo
and Moreno, Montserrat and Ramalho, Leandra N. and Colmenero, Jordi
and Marí, Montserrat and Clària, Joan and Jiménez, Wladimiro and
Arroyo, Vicente and Brenner, David A. and Ginès, Pere},
title = {Bradykinin Attenuates Hepatocellular Damage and Fibrosis in Rats
With Chronic Liver Injury},
journal = {Gastroenterology},
year = {2007},
volume = {133},
pages = {2019--2028},
number = {6},
month = dec,
abstract = {Background & Aims: Recent studies have suggested that the kallikrein-kinin
system regulates tissue fibrogenesis. We hypothesize that bradykinin
(BK), the main effector peptide of this system, regulates hepatic
fibrogenesis. Methods: Kallikrein-kinin system components were studied
by quantitative reverse-transcription polymerase chain reaction analysis,
immunohistochemistry, and Western blotting. The effect of bradykinin
on liver injury was studied by infusing saline or bradykinin (1 and
100 ng/kg/min) through a subcutaneous pump into carbon tetrachloride-treated
rats and mice treated with Fas-stimulating antibody. Bradykinin effects
were studied in cultured hepatic stellate cells (HSCs) and hepatocytes.
Results: Bradykinin receptors and kallikrein-1 were detected in both
normal and fibrotic human livers and HSCs. BK receptors were up-regulated
in fibrotic livers and activated HSCs. Bradykinin infusion reduced
liver damage, as indicated by decreased aminotransferase serum levels
and reduced histologic necroinflammatory score without inducing changes
in arterial pressure. Moreover, bradykinin attenuated hepatic fibrosis,
as indicated by reduced collagen accumulation, smooth muscle [alpha]-actin
content, as well as decreased pro-collagen-[alpha]1(I) and transforming
growth factor-[beta]1 gene expression. Bradykinin infusion reduced
hepatocellular apoptosis induced by anti-Fas-receptor antibody. HSCs
responded to bradykinin with intracellular calcium mobilization.
Bradykinin reduced procollagen-[alpha]1(I) and transforming growth
factor-[beta]1 gene expression and induced matrix metalloproteinase-2
activation. Finally, BK induced prosurvival and proliferative intracellular
signaling in primary hepatocytes. Conclusions: Bradykinin attenuates
liver damage and fibrosis development in a rat model of chronic liver
injury. Therefore, activation of the kallikrein-kinin system may
be a new therapeutic approach to the management of chronic liver
disease.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4PRYFW2-2/2/98af67291f1f262c2742449700db579f}
}
@ARTICLE{Sanden2009,
author = {Sanden, Monica and Olsvik, Pål},
title = {Intestinal cellular localization of PCNA protein and CYP1A mRNA in
Atlantic salmon Salmo salar L. exposed to a model toxicant},
journal = {BMC Physiology},
year = {2009},
volume = {9},
pages = {3},
number = {1},
abstract = {BACKGROUND:The aim of the study was to examine the intestinal cellular
localization of proliferating cell nuclear antigen (PCNA) and cytochrome
P450 A1 (CYP1A) expression in Atlantic salmon Salmo salar L. exposed
to a model toxicant. The stress response was induced by intraperitoneal
injection of four salmon with a single dose (50 mg/kg) of the CYP1A
inducer ß-naphthoflavone (BNF) and intestinal tissue (mid and distal
intestine; MI and DI) was sampled seven days later. Samples for histology
and gene transcription analysis were collected from four exposed
fish and four control fish. PCNA was assessed by immunohistochemistry,
CYP1A mRNA was studied by in situ hybridization (ISH) and finally
the transcription of five genes was quantified by real-time quantitative
RT-PCR (real-time RT-PCR); two detoxifying genes (CYP1A and glutathione
S-transferase; GST), a stress marker gene (heat shock protein 70;
HSP70), PCNA and a gene marker of apoptosis (caspase 6A).RESULTS:PCNA
protein and CYP1A mRNA were successfully localized in the intestinal
cells (MI) of both experimental groups. At the cellular level, BNF
significantly lowered intestinal cell proliferation and increased
the CYP1A mRNA levels compared to the control group. The real-time
RT-PCR data, which showed an increased mRNA expression both in the
MI and DI of 139- and 62-fold, respectively, confirmed the increased
cellular CYP1A mRNA levels detected using ISH. HSP70 expression was
also up-regulated in the exposed fish. The other examined genes did
not show any differential regulation in the experimental fish group.CONCLUSION:This
study showed that CYP1A mRNA had a specific intestinal cellular transcription
pattern in Atlantic salmon exposed to BNF. At the cellular level
CYP1A mRNA expression was always observed at or around the cell nucleus
close to the basolateral cell membrane and at the tissue level CYP1A
mRNA expression was most frequently observed in the basal and apex
area of the intestinal folds. Taken together, a link between the
intestinal detoxification system (CYP1A) and cell renewal system
(PCNA) is indicated with these two processes being inversely correlated
in BNF exposed fish.},
doi = {10.1186/1472-6793-9-3},
issn = {1472-6793},
pubmedid = {19309504},
url = {http://www.biomedcentral.com/1472-6793/9/3}
}
@ARTICLE{Sander2005,
author = {Sander, Birgitta and Flygare, Jenny and Porwit-MacDonald, Anna and
Smith, C.I. Edvard and Emanuelsson, Emma and Kimby, Eva and Liden,
Johan and Christensson, Birger},
title = {Mantle cell lymphomas with low levels of cyclin D1 long mRNA transcripts
are highly proliferative and can be discriminated by elevated cyclin
A2 and cyclin B1},
journal = {Int. J. Cancer},
year = {2005},
volume = {117},
pages = {418--430},
number = {3},
abstract = {Abstract 10.1002/ijc.21166.abs The role of transcript variants of
cyclin D1 in cancer biology is unclear. Most tumors with high levels
of cyclin D1 express 2 transcripts due to alternative splicing: one
full-length transcript of 4.4 kb and one short transcript of approximately
1.7 kb. The short transcript lacks part of the 3′UTR region regulating
mRNA stability and has a longer half-life. In our study, the contribution
of each of these mRNAs to gene expression and cell proliferation
has been investigated in mantle cell lymphoma (MCL), a B cell lymphoma
characterized by a specific gene translocation resulting in enhanced
expression of cyclin D1. A subset of MCL tumors with low levels of
the long cyclin D1 transcript (cyclin D1 3′UTR) was identified
by quantitative PCR and by oligonucleotide array hybridization. This
tumor-subset had 3.4-fold higher levels of the short form of cyclin
D1 mRNA (p < 0.0001) and had higher expression of cyclin D1 protein.
Gene expression analysis identified a number of cell-cycle regulatory
genes as upregulated. There was a significant difference in frequencies
of cyclin B1 (p = 0.0006) and cyclin A2 (p = 0.0006) positive cells
that discriminated MCL with low cyclin D1 3′UTR from other highly
proliferative MCL. Among differentially expressed genes, there was
a highly upregulated gene with homology to the group of cell-cycle
promoting E2F transcription partners, E2F_TDP5. Several of the upregulated
genes, such as TOP2A, AURORA A and RRM2 may influence a response
to therapy. Identification of MCL with low cyclin D1 3′UTR is important
because it seems to be associated with shorter overall survival.
© 2005 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {mantle cell lymphoma, cyclins, CCND1 3′UTR, pro-liferation, expression
profiling, micro array},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.21166}
}
@ARTICLE{Sanders2000,
author = {Sanders, Giles H. W. and Manz, Andreas},
title = {Chip-based microsystems for genomic and proteomic analysis},
journal = {TrAC Trends in Analytical Chemistry},
year = {2000},
volume = {19},
pages = {364--378},
number = {6},
month = jun,
issn = {0165-9936},
keywords = {Micro total analysis systems, DNA, Protein, Microarrays, Microstructures,
Microfluidics, Hybridisation, PCR, Sequencing, Sizing separations,
Electrophoresis, Immunoassays, Mass spectrometry, Two-dimensional
polyacrylamide electrophoresis},
url = {http://www.sciencedirect.com/science/article/B6V5H-40B2JFS-3/2/86c6d47831d8a69e6a2ef10c9bf13789}
}
@ARTICLE{Sanders2005,
author = {Sanders, J. M. and Burka, L. T. and Smith, C. S. and Black, W. and
James, R. and Cunningham, M. L.},
title = {Differential Expression of CYP1A, 2B, and 3A Genes in the F344 Rat
following Exposure to a Polybrominated Diphenyl Ether Mixture or
Individual Components},
journal = {Toxicol. Sci.},
year = {2005},
volume = {88},
pages = {127--133},
number = {1},
month = nov,
abstract = {Polybrominated diphenyl ethers (PBDEs), used as flame retardants,
have been detected in the environment and in mammalian tissues and
fluids. Evidence indicates that PBDE mixtures induce CYPs through
aryl hydrocarbon receptor (AhR)-dependent and -independent pathways.
The present work has investigated the effects of individual components
of a commercial PBDE mixture (DE71) on expression of CYP1A1, a biomarker
for activation of the AhR (dioxin-like), and CYP2B and CYP3A, biomarkers
for activation of the constitutive androstane and pregnanexreceptors
(CAR and PXR), respectively, in the rat. Male F344 rats were dosed
orally on three consecutive days with either DE71, PBDE components,
2,2',4,4'-tetraBDE (BDE47), 2,2',4,4',5-pentaBDE (BDE99), 2,2',4,4',5,5'-hexaBDE
(BDE153), representative polybrominated dibenzofurans (PBDFs) present
in DE71, or reference PCBs. Differential expression of target genes
was determined in liver 24 h after the last dose. Quantitative PCR
analysis indicated up-regulation of CYP1A1 by DE71; however, the
response was weak compared to that for dioxin-like PCB126. Individual
PBDE components of DE71 up-regulated CYP1A1 only at the highest administered
dose (100 {micro}mol/kg/day). Representative PBDFs efficiently up-regulated
CYP1A1; therefore, they, along with other PBDFs and polybrominated
dibenzodioxins detected in DE71 and individual PBDE components, may
be responsible for most, if not all, dioxin-like properties previously
observed for PBDEs. Conversely, PBDEs appear capable of up-regulating
CYP2B and CYP3A in rats at doses similar to that for non-dioxin-like
PCB153. These results indicate that in vivo PBDE-mediated toxicity
would be better categorized by AhR-independent mechanisms, rather
than the well-characterized AhR-dependent mechanism associated with
exposure to dioxin-like chemicals.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/88/1/127}
}
@ARTICLE{Sanders2009,
author = {Sanders, Laurie H. and Sudhakaran, Julee and Sutton, Mark D.},
title = {The GO system prevents ROS-induced mutagenesis and killing in Pseudomonas
aeruginosa},
journal = {FEMS Microbiology Letters},
year = {2009},
volume = {294},
pages = {89--96},
number = {1},
abstract = {Abstract Inactivation of the Pseudomonas aeruginosa mutM, mutY, or
mutT gene conferred a 2.4-, 17.2-, or 38.1-fold increase in spontaneous
mutation frequency, respectively. Importantly, the mutY and mutT
strains each displayed a robust H2O2-induced mutation frequency.
In addition, the mutM, mutY, and mutT mutations severely sensitized
P. aeruginosa to killing by H2O2, suggesting that these gene products
act to repair one or more cytotoxic lesions in P. aeruginosa. Nucleotide
sequence analysis of a fragment of the rpoB gene from rifampicin
resistant mutM-, mutY-, and, mutT-deficient strains was consistent
with this conclusion. These findings are discussed in terms of possible
roles for mutM, mutY, and mutT in contributing to survival and mutagenesis
of P. aeruginosa colonizing the airways of cystic fibrosis patients.},
issn = {1574-6968},
keywords = {base excision repair, DNA damage, mutations, reactive oxygen species,
pathogenesis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2009.01550.x}
}
@ARTICLE{Sanders2011,
author = {Sanders, Rebecca and Huggett, Jim F. and Bushell, Claire A. and Cowen,
Simon and Scott, Daniel J. and Foy, Carole A.},
title = {Evaluation of Digital PCR for Absolute DNA Quantification},
journal = {Analytical Chemistry},
year = {2011},
volume = {83},
pages = {6474-6484},
number = {17},
abstract = { The emerging technique of microfluidic digital PCR (dPCR) offers
a unique approach to real-time quantitative PCR for measuring nucleic
acids that may be particularly suited for low-level detection. In
this study, we evaluated the quantitative capabilities of dPCR when
measuring small amounts (<200 copies) of DNA and investigated parameters
influencing technical performance. We used various DNA templates,
matrixes, and assays to evaluate the precision, sensitivity and reproducibility
of dPCR, and demonstrate that this technique can be highly reproducible
when performed at different times and when different primer sets
are targeting the same molecule. dPCR exhibited good analytical sensitivity
and was reproducible outside the range recommended by the instrument
manufacturer; detecting 16 estimated targets with high precision.
The inclusion of carrier had no effect on this estimated quantity,
but did improve measurement precision. We report disagreement when
using dPCR to measure different template types and when comparing
the estimated quantities by dPCR and UV spectrophotometry. Finally,
we also demonstrate that preamplification can impose a significant
measurement bias. These findings provide an independent assessment
of low copy molecular measurement using dPCR and underline important
factors for consideration in dPCR experimental design. },
doi = {10.1021/ac103230c},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac103230c},
url = {http://pubs.acs.org/doi/abs/10.1021/ac103230c}
}
@ARTICLE{Sanderson2010,
author = {Sanderson, Linda M. and Boekschoten, Mark V. and Desvergne, Beatrice
and Muller, Michael and Kersten, Sander},
title = {Transcriptional profiling reveals divergent roles of PPAR{alpha}
and PPAR{beta}/{delta} in regulation of gene expression in mouse
liver},
journal = {Physiol Genomics},
year = {2010},
volume = {41},
pages = {42--52},
number = {1},
month = mar,
abstract = {Little is known about the role of the transcription factor peroxisome
proliferator-activated receptor (PPAR) {beta}/{delta} in liver. Here
we set out to better elucidate the function of PPAR{beta}/{delta}
in liver by comparing the effect of PPAR{alpha} and PPAR{beta}/{delta}
deletion using whole genome transcriptional profiling and analysis
of plasma and liver metabolites. In fed state, the number of genes
altered by PPAR{alpha} and PPAR{beta}/{delta} deletion was similar,
whereas in fasted state the effect of PPAR{alpha} deletion was much
more pronounced, consistent with the pattern of gene expression of
PPAR{alpha} and PPAR{beta}/{delta}. Minor overlap was found between
PPAR{alpha}- and PPAR{beta}/{delta}-dependent gene regulation in
liver. Pathways upregulated by PPAR{beta}/{delta} deletion were connected
to innate immunity and inflammation. Pathways downregulated by PPAR{beta}/{delta}
deletion included lipoprotein metabolism and various pathways related
to glucose utilization, which correlated with elevated plasma glucose
and triglycerides and reduced plasma cholesterol in PPAR{beta}/{delta}-/-
mice. Downregulated genes that may underlie these metabolic alterations
included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent
novel PPAR{beta}/{delta} target genes. In contrast to PPAR{alpha}-/-
mice, no changes in plasma free fatty acid, plasma {beta}-hydroxybutyrate,
liver triglycerides, and liver glycogen were observed in PPAR{beta}/{delta}-/-
mice. Our data indicate that PPAR{beta}/{delta} governs glucose utilization
and lipoprotein metabolism and has an important anti-inflammatory
role in liver. Overall, our analysis reveals divergent roles of PPAR{alpha}
and PPAR{beta}/{delta} in regulation of gene expression in mouse
liver.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/41/1/42}
}
@ARTICLE{Sanderson2009,
author = {Sanderson, Linda M. and Degenhardt, Tatjana and Koppen, Arjen and
Kalkhoven, Eric and Desvergne, Beatrice and Muller, Michael and Kersten,
Sander},
title = {Peroxisome Proliferator-Activated Receptor {beta}/{delta} (PPAR{beta}/{delta})
but Not PPAR{alpha} Serves as a Plasma Free Fatty Acid Sensor in
Liver},
journal = {Mol. Cell. Biol.},
year = {2009},
volume = {29},
pages = {6257--6267},
number = {23},
month = dec,
abstract = {Peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is
an important transcription factor in liver that can be activated
physiologically by fasting or pharmacologically by using high-affinity
synthetic agonists. Here we initially set out to elucidate the similarities
in gene induction between Wy14643 and fasting. Numerous genes were
commonly regulated in liver between the two treatments, including
many classical PPAR{alpha} target genes, such as Aldh3a2 and Cpt2.
Remarkably, several genes induced by Wy14643 were upregulated by
fasting independently of PPAR{alpha}, including Lpin2 and St3gal5,
suggesting involvement of another transcription factor. Using chromatin
immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets
of PPAR{beta}/{delta} during fasting, whereas Aldh3a2 and Cpt2 were
exclusive targets of PPAR{alpha}. Binding of PPAR{beta}/{delta} to
the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA)
concentration, consistent with activation of PPAR{beta}/{delta} by
plasma FFAs. Subsequent experiments using transgenic and knockout
mice for Angptl4, a potent stimulant of adipose tissue lipolysis,
confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5
expression levels via PPAR{beta}/{delta}. In contrast, the data did
not support activation of PPAR{alpha} by plasma FFAs. The results
identify Lpin2 and St3gal5 as novel PPAR{beta}/{delta} target genes
and show that upregulation of gene expression by PPAR{beta}/{delta}
is sensitive to plasma FFA levels. In contrast, this is not the case
for PPAR{alpha}, revealing a novel mechanism for functional differentiation
between PPARs.},
url = {http://mcb.asm.org/cgi/content/abstract/29/23/6257}
}
@ARTICLE{Sandford2011,
author = {Sandford, Erin and Orr, Megan and Balfanz, Emma and Bowerman, Nate
and Li, Xianyao and Zhou, Huaijun and Johnson, Timothy and Kariyawasam,
Subhashinie and Liu, Peng and Nolan, Lisa and Lamont, Susan},
title = {Spleen transcriptome response to infection with avian pathogenic
Escherichia coli in broiler chickens},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {469},
number = {1},
abstract = {BACKGROUND:Avian pathogenic Escherichia coli (APEC) is detrimental
to poultry health and its zoonotic potential is a food safety concern.
Regulation of antimicrobials in food-production animals has put greater
focus on enhancing host resistance to bacterial infections through
genetics. To better define effective mechanism of host resistance,
global gene expression in the spleen of chickens, harvested at two
times post-infection (PI) with APEC, was measured using microarray
technology, in a design that will enable investigation of effects
of vaccination, challenge, and pathology level.RESULTS:There were
1,101 genes significantly differentially expressed between severely
infected and non-infected groups on day 1 PI and 1,723 on day 5 PI.
Very little difference was seen between mildly infected and non-infected
groups on either time point. Between birds exhibiting mild and severe
pathology, there were 2 significantly differentially expressed genes
on day 1 PI and 799 on day 5 PI. Groups with greater pathology had
more genes with increased expression than decreased expression levels.
Several predominate immune pathways, Toll-like receptor, Jak-STAT,
and cytokine signaling, were represented between challenged and non-challenged
groups. Vaccination had, surprisingly, no detectible effect on gene
expression, although it significantly protected the birds from observable
gross lesions. Functional characterization of significantly expressed
genes revealed unique gene ontology classifications during each time
point, with many unique to a particular treatment or class contrast.CONCLUSIONS:More
severe pathology caused by APEC infection was associated with a high
level of gene expression differences and increase in gene expression
levels. Many of the significantly differentially expressed genes
were unique to a particular treatment, pathology level or time point.
The present study not only investigates the transcriptomic regulations
of APEC infection, but also the degree of pathology associated with
that infection. This study will allow for greater discovery into
host mechanisms for disease resistance, providing targets for marker
assisted selection and advanced drug development.},
doi = {10.1186/1471-2164-12-469},
issn = {1471-2164},
pubmedid = {21951686},
url = {http://www.biomedcentral.com/1471-2164/12/469}
}
@ARTICLE{Sandu2011,
author = {Sandu, Cristina and Hicks, David and Felder-Schmittbuhl, Marie-Paule},
title = {Rat photoreceptor circadian oscillator strongly relies on lighting
conditions},
journal = {European Journal of Neuroscience},
year = {2011},
volume = {34},
pages = {507--516},
number = {3},
abstract = {Mammalian retina harbours a self-sustained circadian clock able to
synchronize to the light : dark (LD) cycle and to drive cyclic
outputs such as night-time melatonin synthesis. Clock genes are expressed
in distinct parts of the tissue, and it is presently assumed that
the retina contains several circadian oscillators. However, molecular
organization of cell type-specific clockworks has been poorly investigated.
Here, we questioned the presence of a circadian clock in rat photoreceptors
by studying 24-h kinetics of clock and clock output gene expression
in whole photoreceptor layers isolated by vibratome sectioning. To
address the importance of light stimulation towards photoreceptor
clock properties, animals were exposed to 12Â :Â 12Â h LD cycle or
36 h constant darkness. Clock, Bmal1, Per1, Per2, Cry1, Cry2, RevErbα
and Rorβ clock genes were all found to be expressed in photoreceptors
and to display rhythmic transcription in LD cycle. Clock genes in
whole retinas, used as a reference, also showed rhythmic expression
with marked similarity to the profiles in pure photoreceptors. In
contrast, clock gene oscillations were no longer detectable in photoreceptor
layers after 36 h darkness, with the exception of Cry2 and Rorβ.
Importantly, transcripts from two well-characterized clock output
genes, Aanat (arylalkylamine N-acetyltransferase) and c-fos, retained
sustained rhythmicity. We conclude that rat photoreceptors contain
the core machinery of a circadian oscillator likely to be operative
and to drive rhythmic outputs under exposure to a 24-h LD cycle.
Constant darkness dramatically alters the photoreceptor clockwork
and circadian functions might then rely on inputs from extra-photoreceptor
oscillators.},
doi = {10.1111/j.1460-9568.2011.07772.x},
issn = {1460-9568},
keywords = {circadian rhythm, clock gene, photoreceptor, rat, retina},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2011.07772.x}
}
@ARTICLE{Sandusky2009,
author = {Sandusky, G. and Dumaual, C. and Cheng, L.},
title = {Review Paper: Human Tissues for Discovery Biomarker Pharmaceutical
Research: The Experience of the Indiana University Simon Cancer Center--Lilly
Research Labs Tissue/Fluid BioBank},
journal = {Veterinary Pathology},
year = {2009},
volume = {46},
pages = {2--9},
number = {1},
month = jan,
url = {http://vet.sagepub.com}
}
@ARTICLE{Sanford2009,
author = {Sanford, Jeremy R. and Wang, Xin and Mort, Matthew and VanDuyn, Natalia
and Cooper, David N. and Mooney, Sean D. and Edenberg, Howard J.
and Liu, Yunlong},
title = {Splicing factor SFRS1 recognizes a functionally diverse landscape
of RNA transcripts},
journal = {Genome Res.},
year = {2009},
volume = {19},
pages = {381--394},
number = {3},
month = mar,
abstract = {Metazoan genes are encrypted with at least two superimposed codes:
the genetic code to specify the primary structure of proteins and
the splicing code to expand their proteomic output via alternative
splicing. Here, we define the specificity of a central regulator
of pre-mRNA splicing, the conserved, essential splicing factor SFRS1.
Cross-linking immunoprecipitation and high-throughput sequencing
(CLIP-seq) identified 23,632 binding sites for SFRS1 in the transcriptome
of cultured human embryonic kidney cells. SFRS1 was found to engage
many different classes of functionally distinct transcripts including
mRNA, miRNA, snoRNAs, ncRNAs, and conserved intergenic transcripts
of unknown function. The majority of these diverse transcripts share
a purine-rich consensus motif corresponding to the canonical SFRS1
binding site. The consensus site was not only enriched in exons cross-linked
to SFRS1 in vivo, but was also enriched in close proximity to splice
sites. mRNAs encoding RNA processing factors were significantly overrepresented,
suggesting that SFRS1 may broadly influence the post-transcriptional
control of gene expression in vivo. Finally, a search for the SFRS1
consensus motif within the Human Gene Mutation Database identified
181 mutations in 82 different genes that disrupt predicted SFRS1
binding sites. This comprehensive analysis substantially expands
the known roles of human SR proteins in the regulation of a diverse
array of RNA transcripts.},
url = {http://genome.cshlp.org/cgi/content/abstract/19/3/381}
}
@ARTICLE{Sanso2008,
author = {Sanso, Miriam and Gogol, Madelaine and Ayte, Jose and Seidel, Chris
and Hidalgo, Elena},
title = {Transcription Factors Pcr1 and Atf1 Have Distinct Roles in Stress-
and Sty1-Dependent Gene Regulation},
journal = {Eukaryot. Cell},
year = {2008},
volume = {7},
pages = {826--835},
number = {5},
month = may,
abstract = {The mitogen-activated protein kinase Sty1 is essential for the regulation
of transcriptional responses that promote cell survival in response
to different types of environmental stimuli in Schizosaccharomyces
pombe. Upon stress activation, Sty1 reversibly accumulates in the
nucleus, where it stimulates gene expression via the Atf1 transcription
factor. The Atf1 protein forms a heterodimer with Pcr1, but the specific
role of this association is controversial. We have carried out a
comparative analysis of strains lacking these proteins individually.
We demonstrate that Atf1 and Pcr1 have similar but not identical
roles in S. pombe, since cells lacking Pcr1 do not share all the
phenotypes reported for {Delta}atf1 cells. Northern blot and microarray
analyses demonstrate that the responses to specific stresses of cells
lacking either Pcr1 or Atf1 do not fully overlap, and even though
most Atf1-dependent genes induced by osmotic stress are also Pcr1
dependent, a subset of genes require only the presence of Atf1 for
their induction. Whereas binding of Atf1 to most stress-dependent
genes requires the presence of Pcr1, we demonstrate here that Atf1
can bind to the Pcr1-independent promoters in a {Delta}pcr1 strain
in vivo. Furthermore, these analyses show that both proteins have
a global repressive effect on stress-dependent and stress-independent
genes.},
url = {http://ec.asm.org/cgi/content/abstract/7/5/826}
}
@ARTICLE{SantaMaria2011,
author = {Santa Maria, Peter L. and Redmond, Sharon L. and McInnes, Russell
L. and Atlas, Marcus D. and Ghassemifar, Reza},
title = {Tympanic membrane wound healing in rats assessed by transcriptome
profiling},
journal = {The Laryngoscope},
year = {2011},
volume = {121},
pages = {2199--2213},
number = {10},
abstract = {Objectives/Hypothesis:The aim of this study is to elucidate transcriptional
changes that occur in response to tympanic membrane (TM) perforation
in rats and to infer key genes and molecular events in the healing
process.Study Design:A prospective cohort study of 393 male Sprague-Dawley
(Rattus norvegicus) rats.Methods:Sprague-Dawley rats were randomly
allocated into either control or perforation groups spanning a 7-day
time period. Perforation groups consisted of 12-hour, 24-hour, 36-hour,
2-day, 3-day, 4-day, 5-day, six-day, and 7-day time points. The left
TMs of all perforation groups were perforated and the RNA extracted
at the specified time point postperforation. Subsequent analysis
was performed using Agilent's 4 × 44 k whole rat genome arrays (40
in total) to assess wound-healing gene expression over a 7-day time
period.Results:Over a 7-day time course and at nine time points that
encompassed the wounding and progression of healing, a total of 3,262
genes were differentially expressed. In this study the transcripts
most upregulated occurred at 12 hours. These were Stefin A2 (344-fold),
Stefin 2 (143-fold), and Natriuretic peptide precursor type B (222-fold).
Those most downregulated also occurred at 12 hours. These were alcohol
dehydrogenase 7 (13.1-fold) and gamma-butyrobetaine hydroxylase (10.4-fold).
Results were validated by quantitative real-time polymerase chain
reaction.Conclusions:The findings of this study provide a baseline
against which to identify disease-related molecular signatures, biomarkers,
and to develop new treatments for TM conditions based on molecular
evidence.},
doi = {10.1002/lary.22150},
issn = {1531-4995},
keywords = {Microarray, wound healing, tympanic membrane, rats, growth factor,
transcriptome, Evidence Level: 2b},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/lary.22150}
}
@ARTICLE{Santa-Maria2010,
author = {Santa-Maria, Ismael and Avila, Jesus and Rabano, Alberto},
title = {Differential gene expression analysis of human entorhinal cortex
support a possible role of some extracellular matrix proteins in
the onset of Alzheimer disease},
journal = {Neuroscience Letters},
year = {2010},
volume = {468},
pages = {225--228},
number = {3},
month = jan,
abstract = {The onset of Alzheimer's disease (AD) has been associated with the
specific vulnerability of neurons in the upper layers of the entorhinal
cortex. To define the molecular characteristics of those neurons,
we have used microarrays to define the gene expression in that region.
In this way, we identified several genes that are expressed distinctly
in the upper and lower layers of the entorhinal cortex. These include
the genes encoding the matrix Gla protein, collagen type 1[alpha]2,
reelin, semaphorin 3C or the relaxin receptor, all related to the
extracellular matrix. Thus, differences in the extracellular matrix
components between the upper and lower layers of the entorhinal cortex
may in part explain the vulnerability of neurons present in the upper
layers of this brain region in disorders like AD.},
issn = {0304-3940},
keywords = {Alzheimer disease, Entorhinal cortex, Microarrays, Extracellular matrix},
url = {http://www.sciencedirect.com/science/article/B6T0G-4XPB72Y-1/2/25594de9dd7ff7d0a49a4aea3c281a82}
}
@ARTICLE{Santana-Lemos2011,
author = {Santana-Lemos, Barbara Amelia and de Lima Lange, Ana Paula Alencar
and de Lira Benicio, Mariana Tereza and Jose, Thiago Donizete da
Silva and Lucena-Araujo, Antonio Roberto and Krause, Alexandre and
Thome, Carolina Hassibe and Rego, Eduardo Magalhaes},
title = {The CEBPA gene is down-regulated in acute promyelocytic leukemia
and its upstream promoter, but not the core promoter, is highly methylated},
journal = {Haematologica},
year = {2011},
volume = {96},
pages = {617--620},
number = {4},
month = apr,
abstract = {Impairment of CCAAT Enhancer Binding Protein alpha (CEBPA) function
is a common finding in acute myeloid leukemia; nevertheless, its
relevance for acute promyelocytic leukemia pathogenesis is unclear.
We analyzed the expression and assessed the methylation status of
the core and upstream promoters of CEBPA in acute promyelocytic leukemia
at diagnosis. Patients with acute promyelocytic leukemia (n=18) presented
lower levels of CEBPA expression compared to healthy controls (n=5),
but higher levels than those in acute myeloid leukemia with t(8;21)
(n=9) and with inv(16) (n=5). Regarding the core promoter, we detected
no methylation in 39 acute promyelocytic leukemia samples or in 8
samples from controls. In contrast, analysis of the upstream promoter
showed methylation in 37 of 39 samples, with 17 patients showing
methylation levels over 30%. Our results corroborate data obtained
in animal models showing that CEBPA is down-regulated in acute promyelocytic
leukemia stem cells and suggest that epigenetic mechanisms may be
involved.},
comment = {10.3324/haematol.2010.028365},
url = {http://www.haematologica.org/cgi/content/abstract/96/4/617}
}
@ARTICLE{Santarelli2011,
author = {Santarelli, Danielle M. and Beveridge, Natalie J. and Tooney, Paul
A. and Cairns, Murray J.},
title = {Upregulation of Dicer and MicroRNA Expression in the Dorsolateral
Prefrontal Cortex Brodmann Area 46 in Schizophrenia},
journal = {Biological Psychiatry},
year = {2011},
volume = {69},
pages = {180--187},
number = {2},
month = jan,
abstract = {Background MicroRNA (miRNA) are capable of regulating multitudes of
target genes and are essential factors in mediating healthy neurodevelopment.
We hypothesize that abnormal miRNA levels contribute to the complex
global changes in gene expression that underlie the pathophysiology
of schizophrenia.Methods With a commercial bead array platform, we
investigated miRNA expression in 74 samples of postmortem dorsolateral
prefrontal cortex (Brodmann Area 46) (n = 37 matched pairs schizophrenia/schizoaffective
disorder and control subjects). A subset of differentially expressed
miRNA and genes in the miRNA biogenesis pathway was also analyzed
with quantitative reverse transcription-polymerase chain reaction.
Gene targets of miRNAs demonstrating significantly altered expression
were predicted, and pathways analysis was performed.Results After
correction for multiple testing, microarray analysis identified differential
expression of 28 miRNA in the schizophrenia group. Significantly,
89% of these molecules were elevated in accordance with earlier work
in other brain regions that showed a broad increase in miRNA expression
in schizophrenia. These observations were supported by quantitative
reverse transcription-polymerase chain reaction, for miR-328, miR-17-5p,
miR-134, miR-652, miR-382, and miR-107 and were consistent with a
schizophrenia-associated increase in miRNA processing through elevated
Dicer expression. Target and pathways analysis provided insight into
the potential cellular effects, with particular enrichment of miRNA
targets in axon guidance and long-term potentiation.Conclusions These
results suggest that schizophrenia is associated with altered miRNA
biogenesis and expression, which might have important implications
in the complex pathophysiology of the disorder.},
booktitle = {Postmortem Studies of Psychosis: Status, Opportunities, and Challenges},
issn = {0006-3223},
keywords = {BA46, dicer, gene silencing, microRNA, neuropathology, schizophrenia},
url = {http://www.sciencedirect.com/science/article/pii/S0006322310009996}
}
@ARTICLE{Santegoets2008,
author = {Santegoets, Lindy A.M. and van Seters, Manon and Heijmans-Antonissen,
Claudia and KleinJan, Alex and van Beurden, Marc and Ewing, Patricia
C. and Kühne, Liesbeth C.M. and Beckmann, Ilse and Burger, Curt
W. and Helmerhorst, Theo J.M. and Blok, Leen J.},
title = {Reduced local immunity in HPV-related VIN: Expression of chemokines
and involvement of immunocompetent cells},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {616--622},
number = {3},
abstract = {Abstract 10.1002/ijc.23545.abs Usual type VIN is a premalignant disorder
caused by persistent HPV infection. High prevalence of VIN in immuno-suppressed
women suggests that a good innate and adaptive immune response is
important for defense against HPV. Here, we explored expression levels
of chemokines and related these to the presence or absence of immuno-competent
cells (dendritic and T-cells) in affected (HPV-positive VIN) and
non-affected (HPV-negative) vulvar tissues from the same patients.
Combining microarray data with quantitative real-time RT-PCR, it
was observed that several important chemokines were differentially
expressed between VIN and control samples (up-regulation of IL8,
CXCL10, CCL20 and CCL22 and down-regulation of CXCL12, CCL21 and
CCL14). Furthermore, an increased number of mature dendritic cells
(CD208+) seemed to be bottled up in the dermis, and although a T-cell
response (increased CD4+ and CD8+ cells) was observed in VIN, a much
larger response is required to clear the infection. In summary, it
seems that most mature dendritic cells do not receive the proper
chemokine signal for migration and will stay in the dermis, not able
to present viral antigen to naive T-cells in the lymph node. Consequently
the adaptive immune response diminishes, resulting in a persistent
HPV infection with increased risk for neoplasia. © 2008 Wiley-Liss,
Inc.},
issn = {1097-0215},
keywords = {vulvar intraepithelial neoplasia, HPV, immune response, chemokines},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23545}
}
@ARTICLE{Santegoets2007,
author = {Santegoets, Lindy A.M. and Seters, Manon van and Helmerhorst, Theo
J.M. and Heijmans-Antonissen, Claudia and Hanifi-Moghaddam, Payman
and Ewing, Patricia C. and van IJcken, Wilfred F.J. and van der Spek,
Peter J. and van der Meijden, Willem I. and Blok, Leen J.},
title = {HPV related VIN: Highly proliferative and diminished responsiveness
to extracellular signals},
journal = {Int. J. Cancer},
year = {2007},
volume = {121},
pages = {759--766},
number = {4},
abstract = {Abstract 10.1002/ijc.22769.abs Vulvar intraepithelial neoplasia (VIN)
is a premalignant disorder caused by human papillomaviruses. Basic
knowledge about the molecular pathogenesis of VIN is sparse. Therefore,
we have analyzed the gene expression profile of 9 VIN samples in
comparison to 10 control samples by using genome wide Affymetrix
Human U133A plus2 GeneChips. Results were validated by quantitative
real-time RT-PCR analysis and immunostaining of a few representative
genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays
(SAM) showed that 1,497 genes were differentially expressed in VIN
compared to controls. By analyzing the biological processes affected
by the observed differences, we found that VIN appears to be a highly
proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost
all prereplication complex proteins are upregulated. Thereby, VIN
does not seem to depend for its proliferation on paracrine or endocrine
signals. Many receptors (for example ESR1 and AR) and ligands are
downregulated. Furthermore, although VIN is not an invasive disease,
the inhibition of expression of a marked number of cell–cell adhesion
molecules seems to indicate development towards invasion. Upon reviewing
apoptosis and angiogenesis, it was observed that these processes
have not become significantly disregulated in VIN. In conclusion:
although VIN is still a premalignant disease, it already displays
several hallmarks of cancer. © 2007 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {microarray, VIN, vulvar cancer, hallmarks of cancer, gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22769}
}
@ARTICLE{Santegoets2008a,
author = {Santegoets, Saskia J. A. M. and Gibbs, Susan and Kroeze, Kim and
van de Ven, Rieneke and Scheper, Rik J. and Borrebaeck, Carl A. and
de Gruijl, Tanja D. and Lindstedt, Malin},
title = {Transcriptional profiling of human skin-resident Langerhans cells
and CD1a+ dermal dendritic cells: differential activation states
suggest distinct functions},
journal = {J. Leukoc. Biol.},
year = {2008},
volume = {84},
pages = {143--151},
number = {1},
month = jul,
abstract = {In human skin, two main populations of dendritic cells (DC) can be
discriminated: dermal DC (DDC) and epidermal Langerhans cells (LC).
Although extensively studied, most of the knowledge about DDC and
LC phenotype and function is obtained from studying DDC and LC cultured
in vitro or DDC and LC migrated from skin explants. These studies
have left the exact relationship between steady-state human LC and
DDC unclear: in particular, whether CD1a+ DDC represent migrated
LC or whether they constitute a separate subset. To gain further
insight in the kinship between skin-resident CD1a+ DDC and LC, we
analyzed CD1a+ DDC and LC, isolated from steady-state skin samples,
by high-density microarray analysis. Results show that the CD1a+
DDC specifically express markers associated with DDC phenotype, such
as the macrophage mannose receptor, DC-specific ICAM-grabbing nonintegrin,
the scavenger receptor CD36, coagulation factor XIIIa, and chemokine
receptor CCR5, whereas LC specifically express Langerin, membrane
ATPase (CD39), and CCR6, all hallmarks of the LC lineage. In addition,
under steady-state conditions, both DC subsets display a strikingly
different activation status, indicative of distinct functional properties.
CD1a+ DDC exhibit a more activated, proinflammatory, migratory, and
T cell-stimulatory profile, as compared with LC, whereas LC mainly
express molecules involved in cell adhesion and DC retention in the
epidermis. In conclusion, transcriptional profiling is consistent
with the notion that CD1a+ DDC and LC represent two distinct DC subsets
but also that under steady-state conditions, CD1a+ DDC and epidermal
LC represent opposites of the DC activation spectrum.},
url = {http://www.jleukbio.org/cgi/content/abstract/84/1/143}
}
@ARTICLE{Santer2012,
author = {Santer, Deanna M. and Wiedeman, Alice E. and Teal, Thomas H. and
Ghosh, Pradipta and Elkon, Keith B.},
title = {Plasmacytoid Dendritic Cells and C1q Differentially Regulate Inflammatory
Gene Induction by Lupus Immune Complexes},
journal = {J. Immunol.},
year = {2012},
volume = {188},
pages = {902-915},
number = {2},
abstract = {Immune complexes (ICs) play a pivotal role in causing inflammation
in systemic lupus erythematosus (SLE). Yet, it remains unclear what
the dominant blood cell type(s) and inflammation-related gene programs
stimulated by lupus ICs are. To address these questions, we exposed
normal human PBMCs or CD14+ isolated monocytes to SLE ICs in the
presence or absence of C1q and performed microarray analysis and
other tests for cell activation. By microarray analysis, we identified
genes and pathways regulated by SLE ICs that are both type I IFN
dependent and independent. We also found that C1q-containing ICs
markedly reduced expression of the majority of IFN-response genes
and also influenced the expression of multiple other genes induced
by SLE ICs. Surprisingly, IC activation of isolated CD14+ monocytes
did not upregulate CD40 and CD86 and only modestly stimulated inflammatory
gene expression. However, when monocyte subsets were purified and
analyzed separately, the low-abundance CD14dim ("patrolling") subpopulation
was more responsive to ICs. These observations demonstrate the importance
of plasmacytoid dendritic cells, CD14dim monocytes, and C1q as key
regulators of inflammatory properties of ICs and identify many pathways
through which they act.},
doi = {10.4049/jimmunol.1102797},
eprint = {http://www.jimmunol.org/cgi/reprint/188/2/902.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/188/2/902}
}
@ARTICLE{Santi2010,
author = {Santi, Stacey A. and Lee, Hoyun},
title = {The Akt isoforms are present at distinct subcellular locations},
journal = {Am J Physiol Cell Physiol},
year = {2010},
volume = {298},
pages = {C580--591},
number = {3},
month = mar,
abstract = {Akt is involved in the regulation of diverse cellular functions such
as cell proliferation, energy metabolism, and apoptosis. Although
three Akt isoforms are known, the function of each isoform is poorly
understood. To gain a better understanding of each Akt isoform, we
examined the subcellular localization and expression of each isoform
in transformed and nontransformed cells. Akt1 was localized in the
cytoplasm, which is in agreement with the currently accepted model
that cytoplasmic Akt is translocated and activated at the inner leaflet
of the plasma membrane. Interestingly, HEK-293 and HEK-293T cells
contained Akt1 in the nucleus and cytoplasm, respectively, suggesting
that SV40 T-antigen plays a crucial role in the cytoplasmic localization
and activation of Akt1 in HEK-293T. Akt2 was colocalized with the
mitochondria, while Akt3 was localized in both the nucleus and nuclear
membrane. The subcellular localization of the Akt isoforms was not
substantially altered in response to ionizing radiation or EGF. Furthermore,
the ablation of one Akt isoform by small interfering RNA (siRNA)
did not alter the subcellular location of the remaining isoforms,
suggesting that the major function of one isoform is not compensated
for by other isoforms. Together, our data support the notion that
Akt2 and Akt3 are regulated at the mitochondrial and nuclear membranes,
respectively. The mitochondrial localization of Akt2 raises the possibility
that this isoform may be involved in both glucose-based energy metabolism
and suppression of apoptosis, two Akt functions previously identified
with anti-pan-Akt antibodies.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/298/3/C580}
}
@ARTICLE{Santi-Rocca2008,
author = {Santi-Rocca, Julien and Weber, Christian and Guigon, Ghislaine and
Sismeiro, Odile and Coppée, Jean-Yves and Guillén, Nancy},
title = {The lysine- and glutamic acid-rich protein KERP1 plays a role in
Entamoeba histolytica liver abscess pathogenesis},
journal = {Cellular Microbiology},
year = {2008},
volume = {10},
pages = {202--217},
number = {1},
abstract = {Summary The parasite Entamoeba histolytica colonizes the large bowel
where it may persist as an asymptomatic luminal gut infection, which
changes to virulence. Parasite invasion of the intestine leads to
dysentery and spreads to the liver, where amoebae form abscesses.
We took advantage of changes in virulence that occurs after long-term
in vitro culture of E. histolytica strains. Using microarrays, we
concluded that virulence correlates with upregulation of key genes
involved in stress response, including molecular chaperones, ssp1
and peroxiredoxin; as well as the induction of unknown genes encoding
lysine-rich proteins. Seven of these were retained with respect to
their lysine content higher than 25%. Among them, we found KERP1,
formerly identified as associated to parasite surface and involved
in the parasite adherence to host cells. Experimentally induced liver
abscesses, using molecular beacons and protein analysis, allowed
us to draw a parallel between the intricate upregulation of kerp1
gene expression during abscess development and the increased abundance
of KERP1 in virulent trophozoites. Following its characterization
as a marker for the progression of infection, KERP1 was also seen
to be a virulence marker as trophozoites affected in kerp1 expression
by an antisense strategy were unable to form liver abscesses.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2007.01030.x}
}
@ARTICLE{Santini2007,
author = {Santini, Valeria},
title = {A selective activity of DNMTi decitabine on AML1ETO positive cells?},
journal = {Leukemia Research},
year = {2007},
volume = {31},
pages = {741--742},
number = {6},
month = jun,
issn = {0145-2126},
keywords = {p15/INK4B hypermethylation},
url = {http://www.sciencedirect.com/science/article/B6T98-4MW9083-1/2/ed462190430a02fe23f15db80db9b0e4}
}
@ARTICLE{Santora2010,
author = {Santora, Rachel J. and Lie, Mihaela L. and Grigoryev, Dmitry N. and
Nasir, Omer and Moore, Frederick A. and Hassoun, Heitham T.},
title = {Therapeutic distant organ effects of regional hypothermia during
mesenteric ischemia-reperfusion injury},
journal = {J Vasc Surg},
year = {2010},
volume = {52},
pages = {1003--1014},
number = {4},
month = oct,
abstract = {Mesenteric ischemia-reperfusion injury (IRI) leads to systemic inflammation
and multiple organ failure in clinical and laboratory settings. We
investigated the lung structural, functional, and genomic response
to mesenteric IRI with and without regional intraischemic hypothermia
(RIH) in rodents and hypothesized that RIH would protect the lung
and preferentially modulate the distant organ transcriptome under
these conditions. Sprague-Dawley rats underwent sham laparotomy or
superior mesenteric artery occlusion (SMAO) for 60 minutes with or
without RIH. Gut temperature was maintained at 15°-20°C during
SMAO, and systemic normothermia (37°C) was maintained throughout
the study period. At 6 or 24 hours, lung tissue was collected for
(1) histology, (2) myeloperoxidase activity, (3) bronchoalveolar
lavage (BAL) fluid protein concentrations, (4) lung wet/dry ratios,
and (5) total RNA isolation and hybridization to Illumina's Sentrix
BeadChips (>22,000 probes) for gene expression profiling. Significantly
affected genes (false discovery rate <5% and fold change ≥1.5)
were linked to gene ontology (GO) terms using MAPPFinder, and hypothermia-suppressed
genes were further analyzed with Pubmatrix. Mesenteric IRI-induced
lung injury, as evidenced by leukocyte trafficking, alveolar hemorrhage,
and increased BAL protein and wet/dry ratios, and activated a proinflammatory
lung transcriptome compared with sham. In contrast, rats treated
with RIH exhibited lung histology, BAL protein, and wet/dry ratios
similar to sham. At 6 hours, GO analysis identified 232 hypothermia-suppressed
genes related to inflammation, innate immune response, and cell adhesion,
and 33 hypothermia-activated genes related to lipid and amine metabolism
and defense response. Quantitative real-time polymerase chain reaction
validated select array changes in top hypothermia-suppressed genes
lipocalin-2 (lcn-2) and chemokine ligand 1 (CXCL-1), prominent genes
associated with neutrophil activation and trafficking. Therapeutic
hypothermia during SMAO provides distant organ protection and preferentially
modulates the IRI-activated transcriptome in the rat lung. This study
identifies potential novel diagnostic and therapeutic targets of
mesenteric IRI and provides a platform for further mechanistic study
of hypothermic protection at the cellular and subcellular level.
Visceral organ ischemia-reperfusion injury (IRI) is a common clinical
problem in the settings of shock, sepsis, vascular surgery, and organ
transplantation and is a particularly vexing problem in the repair
of complex aortic aneurysms. IRI is associated with considerable
patient morbidity and mortality, for which there are virtually no
therapeutic options. It systematically causes local organ injury
and dysfunction, systemic inflammation, and multiple organ failure.
Clinical trials investigating the efficacy of pharmacologic blockade
of individual downstream inflammatory mediators in critically ill
patients have been largely unsuccessful, and such studies highlight
the need for novel top-down approaches, such as gene expression profiling
for biologic discovery, as well as application of broader therapeutic
interventions, such as targeted hypothermia. In this study, we demonstrate
the potential application of visceral cooling for distant organ protection
during mesenteric IRI, identify broad changes in lung gene expression
under these conditions, and have elucidated potential novel diagnostic
and therapeutic targets for disease targeting.},
issn = {0741-5214},
publisher = {Mosby-Year Book},
refid = {S0741-5214(10)01300-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0741521410013005?showall=true}
}
@ARTICLE{Santoro2011a,
author = {Santoro, Domenico and Bunick, David and Graves, Thomas K. and Campbell,
Karen L.},
title = {Expression and distribution of antimicrobial peptides in the skin
of healthy beagles},
journal = {Veterinary Dermatology},
year = {2011},
volume = {22},
pages = {61--67},
number = {1},
abstract = {Abstract Antimicrobial peptides (AMPs) are small proteins involved
in defense against pathogenic organisms. Defensins and cathelicidin
are the most frequently studied human AMPs. Our goals were to determine
the distribution of AMPs and evaluate their mRNA expression in normal
canine skin. Skin biopsies were taken from six healthy beagles. The
relative transcript level of canine cathelicidin (cCath) and β-defensin
(cBD)-1, cBD2 and cBD3 mRNA was quantified using quantitative real-time
polymerase chain reaction. Indirect immunofluorescence (IIF), using
polyclonal antibodies against cBD2, cBD3 and cCath, was used to evaluate
protein localization in the skin of healthy dogs. The Pfaffl method,
using experimentally determined primer efficiencies of amplification,
was used to determine the expression level of cCath, cBD1 and cDB3
relative to cDB2. The levels of cCath, cBD3 and cBD1 mRNA were 358,
296 and 177 times higher than those of cBD2, respectively. Using
IIF, cBD2 and cBD3 protein fluorescence was detected in all layers
of the epidermis, whereas cCath was detected predominantly in the
stratum granulosum and corneum. In addition, antimicrobial peptide
detection was limited to the infundibular portion of the pilosebaceous
units. We have validated useful methods to evaluate AMPs in canine
skin. Further studies are needed to compare AMP expression in healthy
dogs with that of dogs with inflammatory skin conditions.},
doi = {10.1111/j.1365-3164.2010.00911.x},
issn = {1365-3164},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3164.2010.00911.x}
}
@ARTICLE{Santoro2011,
author = {Domenico Santoro and Rosanna Marsella and David Bunick and Thomas
K. Graves and Karen L. Campbell},
title = {Expression and distribution of canine antimicrobial peptides in the
skin of healthy and atopic beagles},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {144},
pages = {382 - 388},
number = {3–4},
abstract = {Antimicrobial peptides (AMPs) are small immuno-modulatory proteins
important in defense against pathogenic organisms. Defensins and
cathelicidin are the most frequently studied human AMPs. An increase
in AMPs in atopic humans has been reported recently. Our goals were
to determine the distribution of AMPs and evaluate their mRNA and
protein expression in non-lesional (Day 0), acute lesional skin (Day
3) and post-challenged skin after resolution of skin lesions (Day
10) using a canine model of atopic dermatitis (AD). All dogs were
environmentally challenged for three consecutive days with house
dust mite. Clinical evaluation of atopic beagles was performed using
a CADESI score at each time point before and after environmental
challenge. Skin biopsies were taken from six healthy and seven atopic
beagles before and after allergen challenge (Day 0, Day 3 and Day
10). The transcription of canine cathelicidin (cCath) and beta-defensins
(cBD)-1, -2 and -3 mRNA was quantified using quantitative-RT-PCR
while the protein distribution of cBD2, cBD3 and cCath was detected
by indirect immunofluorescence. A significant effect, over-time,
was seen in CADESI score in AD beagles with an increase score after
challenge (Day 3). Quantitative analysis showed a significant difference
in mRNA transcript levels between groups (with atopic dogs having
more than controls) for all AMPs but cBD2. No effect over time was
evident for either group. No significant differences were seen for
the AMP protein patterns of distribution (homogenous distribution).
Although, these results showed no differences in AMP's localization
after allergen exposure in each group; atopic dogs had a higher mRNA
expression of AMPs when compared with healthy dogs, a similar finding
to humans.},
doi = {10.1016/j.vetimm.2011.08.004},
issn = {0165-2427},
keywords = {Antimicrobial peptides},
url = {http://www.sciencedirect.com/science/article/pii/S0165242711002996}
}
@ARTICLE{Santos2010,
author = {Santos, CF and Kurhanewicz, J and Tabatabai, ZL and Simko, JP and
Keshari, KR and Gbegnon, A and Santos, RD and Federman, S and Shinohara,
K and Carroll, PR and Haqq, CM and Swanson, MG},
title = {Metabolic, pathologic, and genetic analysis of prostate tissues:
quantitative evaluation of histopathologic and mRNA integrity after
HR-MAS spectroscopy.},
journal = {NMR Biomed.},
year = {2010},
volume = {23},
pages = {391-8--},
number = {4},
month = may,
abstract = {The impact of high-resolution magic angle spinning (HR-MAS) spectroscopy
on the histopathologic and mRNA integrity of human prostate tissues
was evaluated. Forty prostate tissues were harvested at transrectal
ultrasound (TRUS) guided biopsy (n?=?20) or radical prostatectomy
surgery (n?=?20), snap-frozen on dry ice, and stored at -80°C until
use. Twenty-one samples (n?=?11 biopsy, n?=?10 surgical) underwent
HR-MAS spectroscopy prior to histopathologic and cDNA microarray
analysis, while 19 control samples (n?=?9 biopsy, n?=?10 surgical)
underwent only histopathologic and microarray analysis. Frozen tissues
were sectioned at 14-µm intervals and placed on individual histopathology
slides. Every 8th slide was stained with hematoxylin and eosin (H&E)
and used to target areas of predominantly epithelial tissue on the
remaining slides for mRNA integrity and cDNA microarray analysis.
Histopathologic integrity was graded from 1 (best) to 5 (worst) by
two 'blinded' pathologists. Histopathologic integrity scores were
not significantly different for post-surgical tissues (HR-MAS vs
controls); however, one pathologist's scores were significantly lower
for biopsy tissues following HR-MAS while the other pathologist's
scores were not. mRNA integrity assays were performed using an Agilent
2100 Bioanalyzer and the electrophoretic traces were scored with
an RNA integrity number (RIN) from 1 (degraded) to 10 (intact). RIN
scores were not significantly different for surgical tissues, but
were significantly lower for biopsy tissues following HR-MAS spectroscopy.
The isolated mRNA then underwent two rounds of amplification, conversion
to cDNA, coupling to Cy3 and Cy5 dyes, microarray hybridization,
imaging, and analysis. Significance analysis of microarrays (SAM)
identified no significantly over- or under-expressed genes, including
14 housekeeping genes, between HR-MAS and control samples of surgical
and biopsy tissues (5% false discovery rate). This study demonstrates
that histopathologic and genetic microarray analysis can be successfully
performed on prostate surgical and biopsy tissues following HR-MAS
analysis; however, biopsy tissues are more fragile than surgical
tissues.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20033906}
}
@ARTICLE{Santos2011,
author = {Santos, Fernando and Moreno-Paz, Mercedes and Meseguer, Inmaculada
and Lopez, Cristina and Rossello-Mora, Ramon and Parro, Victor and
Anton, Josefa},
title = {Metatranscriptomic analysis of extremely halophilic viral communities},
journal = {ISME J},
year = {2011},
pages = {--},
month = apr,
issn = {1751-7370},
publisher = {International Society for Microbial Ecology},
url = {http://dx.doi.org/10.1038/ismej.2011.34}
}
@ARTICLE{Santos2009,
author = {Santos, Filipe and Teusink, Bas and Molenaar, Douwe and van Heck,
Maurice and Wels, Michiel and Sieuwerts, Sander and de Vos, Willem
M. and Hugenholtz, Jeroen},
title = {Effect of Amino Acid Availability on Vitamin B12 Production in Lactobacillus
reuteri},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {3930--3936},
number = {12},
month = jun,
abstract = {Recent functional genomics and genome-scale modeling approaches indicated
that B12 production in Lactobacillus reuteri could be improved by
optimization of the medium. Here we show that a series of systematic
single-amino-acid omissions could significantly modulate the production
of B12 from nearly undetectable levels (with omission of isoleucine)
to levels 20-fold higher than the levels previously reported (with
omission of cysteine). Using cDNA microarray experiments, we analyzed
the transcriptional response of L. reuteri to medium lacking cysteine.
The results supported the observed high level of B12 production and
provided new avenues for future improvement of production of vitamin
B12.},
url = {http://aem.asm.org/cgi/content/abstract/75/12/3930}
}
@ARTICLE{Santos2008,
author = {Santos, Filipe and Vera, Jose L. and van der Heijden, Rene and Valdez,
Graciela and de Vos, Willem M. and Sesma, Fernando and Hugenholtz,
Jeroen},
title = {The complete coenzyme B12 biosynthesis gene cluster of Lactobacillus
reuteri CRL1098},
journal = {Microbiology},
year = {2008},
volume = {154},
pages = {81--93},
number = {1},
month = jan,
abstract = {The coenzyme B12 production pathway in Lactobacillus reuteri has been
deduced using a combination of genetic, biochemical and bioinformatics
approaches. The coenzyme B12 gene cluster of Lb. reuteri CRL1098
has the unique feature of clustering together the cbi, cob and hem
genes. It consists of 29 ORFs encoding the complete enzymic machinery
necessary for de novo biosynthesis. Transcriptional analysis showed
it to be expressed as two tandem transcripts of approximately 22
and 4 kb, carrying cobD, cbiABCDETFGHJ, cobA/hemD, cbiKLMNQOP, sirA,
hemACBL, and cobUSC, hemD, cobT, respectively. Both transcripts appear
to be similarly regulated, and under the conditions assayed are induced
in the late-exponential growth phase. Evidence for a regulatory mechanism
of negative feedback inhibition by vitamin B12 itself was observed.
Comparative genomics analysis of the coding sequences showed them
to be most similar to those coding for the anaerobic coenzyme B12
pathways previously characterized in a few representatives of the
genera Listeria and Salmonella. This contrasts with the trusted species
phylogeny and suggests horizontal gene transfer of the B12 biosynthesis
genes. G+C content and codon adaptation index analysis is suggestive
that the postulated transfer of these genes was not a recent event.
Additional comparative genomics and transcriptional analysis of the
sequences acquired during this study suggests a functional link between
coenzyme B12 biosynthesis and reuterin production, which might be
implicated in Lb. reuteri's success in colonizing the gastrointestinal
tract. This information on gene organization, gene transcription
and gene acquisition is relevant for the development of (fermented)
foods and probiotics enriched in B12.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/154/1/81}
}
@ARTICLE{Santos2010a,
author = {Santos, Mário and Cosme, Ana and Becker, Jörg and Medeiros, João
and Mata, Márcia and Moreira, Leonilde},
title = {Absence of functional TolC protein causes increased stress response
gene expression in Sinorhizobium meliloti },
journal = {BMC Microbiology},
year = {2010},
volume = {10},
pages = {180},
number = {1},
abstract = {BACKGROUND:The TolC protein from Sinorhizobium meliloti has previously
been demonstrated to be required for establishing successful biological
nitrogen fixation symbiosis with Medicago sativa. It is also needed
in protein and exopolysaccharide secretion and for protection against
osmotic and oxidative stresses. Here, the transcriptional profile
of free-living S. meliloti 1021 tolC mutant is described as a step
toward understanding its role in the physiology of the cell.RESULTS:Comparison
of tolC mutant and wild-type strains transcriptomes showed 1177 genes
with significantly increased expression while 325 had significantly
decreased expression levels. The genes with an increased expression
suggest the activation of a cytoplasmic and extracytoplasmic stress
responses possibly mediated by the sigma factor RpoH1 and protein
homologues of the CpxRA two-component regulatory system of Enterobacteria,
respectively. Stress conditions are probably caused by perturbation
of the cell envelope. Consistent with gene expression data, biochemical
analysis indicates that the tolC mutant suffers from oxidative stress.
This is illustrated by the elevated enzyme activity levels detected
for catalase, superoxide dismutase and glutathione reductase. The
observed increase in the expression of genes encoding products involved
in central metabolism and transporters for nutrient uptake suggests
a higher metabolic rate of the tolC mutant. We also demonstrated
increased swarming motility in the tolC mutant strain. Absence of
functional TolC caused decreased expression mainly of genes encoding
products involved in nitrogen metabolism and transport.CONCLUSION:This
work shows how a mutation in the outer membrane protein TolC, common
to many bacterial transport systems, affects expression of a large
number of genes that act in concert to restore cell homeostasis.
This finding further underlines the fundamental role of this protein
in Sinorhizobium meliloti biology.},
doi = {10.1186/1471-2180-10-180},
issn = {1471-2180},
pubmedid = {20573193},
url = {http://www.biomedcentral.com/1471-2180/10/180}
}
@ARTICLE{Santos2009a,
author = {dos Santos, Sandra C. and Tenreiro, Sandra and Palma, Margarida and
Becker, Jorg and Sa-Correia, Isabel},
title = {Transcriptomic Profiling of the Saccharomyces cerevisiae Response
to Quinine Reveals a Glucose Limitation Response Attributable to
Drug-Induced Inhibition of Glucose Uptake},
journal = {Antimicrob. Agents Chemother.},
year = {2009},
volume = {53},
pages = {5213--5223},
number = {12},
month = dec,
abstract = {Quinine has been employed in the treatment of malaria for centuries
and is still used against severe Plasmodium falciparum malaria. However,
its interactions with the parasite remain poorly understood and subject
to debate. In this study, we used the Saccharomyces cerevisiae eukaryotic
model to better understand quinine's mode of action and the mechanisms
underlying the cell response to the drug. We obtained a transcriptomic
profile of the yeast's early response to quinine, evidencing a marked
activation of genes involved in the low-glucose response (e.g., CAT8,
ADR1, MAL33, MTH1, and SNF3). We used a low inhibitory quinine concentration
with no detectable effect on plasma membrane function, consistent
with the absence of a general nutrient starvation response and suggesting
that quinine-induced glucose limitation is a specific response. We
have further shown that transport of [14C]glucose is inhibited by
quinine, with kinetic data indicating competitive inhibition. Also,
tested mutant strains deleted for genes encoding high- and low-affinity
hexose transporters (HXT1 to HXT5, HXT8, and HXT10) exhibit resistance
phenotypes, correlating with reduced levels of quinine accumulation
in the mutants examined. These results suggest that the hexose transporters
are facilitators of quinine uptake in S. cerevisiae, possibly through
a competitive inhibition mechanism. Interestingly, P. falciparum
is highly dependent on glucose uptake, which is mediated by the single-copy
transporter PfHT1, a protein with high homology to yeast's hexose
transporters. We propose that PfHT1 is an interesting candidate quinine
target possibly involved in quinine import in P. falciparum, an uptake
mechanism postulated in recent studies to occur through a still-unidentified
importer(s).},
url = {http://aac.asm.org/cgi/content/abstract/53/12/5213}
}
@ARTICLE{Santos-Aberturas2011,
author = {Santos-Aberturas, Javier and Vicente, Claudia M. and Guerra, Susana
M. and Payero, Tamara D. and Martin, Juan F. and Aparicio, Jesus
F.},
title = {Molecular Control of Polyene Macrolide Biosynthesis: DIRECT BINDING
OF THE REGULATOR PimM TO EIGHT PROMOTERS OF PIMARICIN GENES AND IDENTIFICATION
OF BINDING BOXES},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {9150--9161},
number = {11},
month = mar,
abstract = {Control of polyene macrolide production in Streptomyces natalensis
is mediated by the transcriptional activator PimM. This regulator,
which combines an N-terminal PAS domain with a C-terminal helix-turn-helix
motif, is highly conserved among polyene biosynthetic gene clusters.
PimM, truncated forms of the protein without the PAS domain (PimM{Delta}PAS),
and forms containing just the DNA-binding domain (DBD) (PimMDBD)
were overexpressed in Escherichia coli as GST-fused proteins. GST-PimM
binds directly to eight promoters of the pimaricin cluster, as demonstrated
by electrophoretic mobility shift assays. Assays with truncated forms
of the protein revealed that the PAS domain does not mediate specificity
or the distinct recognition of target genes, which rely on the DBD
domain, but significantly reduces binding affinity up to 500-fold.
Transcription start points were identified by 5'-rapid amplification
of cDNA ends, and the binding regions of PimMDBD were investigated
by DNase I protection studies. In all cases, binding took place covering
the -35 hexamer box of each promoter, suggesting an interaction of
PimM and RNA polymerase to cause transcription activation. Information
content analysis of the 16 sequences protected in target promoters
was used to deduce the structure of the PimM-binding site. This site
displays dyad symmetry, spans 14 nucleotides, and adjusts to the
consensus TVGGGAWWTCCCBA. Experimental validation of this binding
site was performed by using synthetic DNA duplexes. Binding of PimM
to the promoter region of one of the polyketide synthase genes from
the Streptomyces nodosus amphotericin cluster containing the consensus
binding site was also observed, thus proving the applicability of
the findings reported here to other antifungal polyketides.},
comment = {10.1074/jbc.M110.182428},
url = {http://www.jbc.org/cgi/content/abstract/286/11/9150}
}
@ARTICLE{Santos-Beneit2011,
author = {Santos-Beneit, Fernando and Barriuso-Iglesias, Monica and Fernandez-Martinez,
Lorena T. and Martinez-Castro, Miriam and Sola-Landa, Alberto and
Rodriguez-Garcia, Antonio and Martin, Juan F.},
title = {The RNA Polymerase Omega Factor RpoZ Is Regulated by PhoP and Has
an Important Role in Antibiotic Biosynthesis and Morphological Differentiation
in Streptomyces coelicolor},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {7586-7594},
number = {21},
abstract = {The RNA polymerase (RNAP) omega factor ({omega}) forms a complex with
the 2{beta}{beta}' core of this enzyme in bacteria. We have characterized
the rpoZ gene of Streptomyces coelicolor, which encodes a small protein
(90 amino acids) identified as the omega factor. Deletion of the
rpoZ gene resulted in strains with a slightly reduced growth rate,
although they were still able to sporulate. The biosynthesis of actinorhodin
and, particularly, that of undecylprodigiosin were drastically reduced
in the {Delta}rpoZ strain, suggesting that expression of these secondary
metabolite biosynthetic genes is dependent upon the presence of RpoZ
in the RNAP complex. Complementation of the {Delta}rpoZ mutant with
the wild-type rpoZ allele restored both phenotype and antibiotic
production. Interestingly, the rpoZ gene contains a PHO box in its
promoter region. DNA binding assays showed that the phosphate response
regulator PhoP binds to such a region. Since luciferase reporter
studies showed that rpoZ promoter activity was increased in a {Delta}phoP
background, it can be concluded that rpoZ is controlled negatively
by PhoP, thus connecting phosphate depletion regulation with antibiotic
production and morphological differentiation in Streptomyces.},
doi = {10.1128/AEM.00465-11},
eprint = {http://aem.asm.org/cgi/reprint/77/21/7586.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/21/7586}
}
@ARTICLE{Santosa2011,
author = {Santosa, Claudia and Rasche, Stefanie and Barakat, Adel and Bellingham,
Shayne A. and Ho, Michael and Tan, Jiangli and Hill, Andrew F. and
Masters, Colin L. and McLean, Catriona and Evin, Geneviève},
title = {Decreased expression of GGA3 Protein in Alzheimer's disease frontal
cortex and increased co-distribution of BACE with the amyloid precursor
protein},
journal = {Neurobiology of Disease},
year = {2011},
volume = {43},
pages = {176--183},
number = {1},
month = jul,
abstract = {BACE initiates the amyloidogenic processing of the amyloid precursor
protein (APP) that results in the production of A[beta] peptides
associated with Alzheimer's disease (AD). Previous studies have indicated
that BACE is elevated in the frontal cortex of AD patients. Golgi-localized
[gamma]-ear containing ADP ribosylation factor-binding proteins (GGA)
control the cellular trafficking of BACE and may alter its levels.
To investigate a link between BACE and GGA expression in AD, frontal
cortex samples from AD (N = 20) and healthy, age-matched controls
(HC, N = 17) were analyzed by immunoblotting. After normalization
to the neuronal marker [beta]-tubulin III, the data indicate an average
two-fold increase of BACE protein (p = 0.01) and a 64% decrease of
GGA3 in the AD group compared to the HC (p = 0.006). GGA1 levels
were also decreased in AD, but a statistical significance was not
achieved. qRT-PCR analysis of GGA3 mRNA showed no difference between
AD and HC. There was a strong correlation between GGA1 and GGA3 in
both AD and HC, but no correlation between BACE and GGA levels. Subcellular
fractionation of AD cortex with low levels of GGA proteins showed
an alteration of BACE distribution and extensive co-localization
with APP. These data suggest that altered compartmentalization of
BACE in AD promotes the amyloidogenic processing of APP.},
booktitle = {Autophagy and protein degradation in neurological diseases},
issn = {0969-9961},
keywords = {BACE1, Secretase, Amyloid precursor protein, Alzheimer's disease},
url = {http://www.sciencedirect.com/science/article/pii/S096999611100091X}
}
@ARTICLE{Santosa2011a,
author = {Claudia Santosa and Stefanie Rasche and Adel Barakat and Shayne A.
Bellingham and Michael Ho and Jiangli Tan and Andrew F. Hill and
Colin L. Masters and Catriona McLean and Geneviève Evin},
title = {Decreased expression of GGA3 Protein in Alzheimer's disease frontal
cortex and increased co-distribution of BACE with the amyloid precursor
protein},
journal = {Neurobiology of Disease},
year = {2011},
volume = {43},
pages = {176 - 183},
number = {1},
note = {Autophagy and protein degradation in neurological diseases},
abstract = {BACE initiates the amyloidogenic processing of the amyloid precursor
protein (APP) that results in the production of Aβ peptides associated
with Alzheimer's disease (AD). Previous studies have indicated that
BACE is elevated in the frontal cortex of AD patients. Golgi-localized
γ-ear containing ADP ribosylation factor-binding proteins (GGA)
control the cellular trafficking of BACE and may alter its levels.
To investigate a link between BACE and GGA expression in AD, frontal
cortex samples from AD (N = 20) and healthy, age-matched
controls (HC, N = 17) were analyzed by immunoblotting.
After normalization to the neuronal marker β-tubulin III, the data
indicate an average two-fold increase of BACE protein (p = 0.01)
and a 64% decrease of GGA3 in the AD group compared to the HC (p = 0.006).
GGA1 levels were also decreased in AD, but a statistical significance
was not achieved. qRT-PCR analysis of GGA3 mRNA showed no difference
between AD and HC. There was a strong correlation between GGA1 and
GGA3 in both AD and HC, but no correlation between BACE and GGA levels.
Subcellular fractionation of AD cortex with low levels of GGA proteins
showed an alteration of BACE distribution and extensive co-localization
with APP. These data suggest that altered compartmentalization of
BACE in AD promotes the amyloidogenic processing of APP.},
doi = {10.1016/j.nbd.2011.03.009},
issn = {0969-9961},
keywords = {BACE1},
url = {http://www.sciencedirect.com/science/article/pii/S096999611100091X}
}
@ARTICLE{Sanz2011,
author = {Sanz, Carmen and Blazquez, Enrique},
title = {New gene targets for glucagon-like peptide-1 during embryonic development
and in undifferentiated pluripotent cells},
journal = {Am J Physiol Endocrinol Metab},
year = {2011},
volume = {301},
pages = {E494-503},
number = {3},
abstract = {In humans, glucagon-like peptide (GLP-1) functions during adult life
as an incretin hormone with anorexigenic and antidiabetogenic properties.
Also, the therapeutic potential of GLP-1 in preventing the adipocyte
hyperplasia associated with obesity and in bolstering the maintenance
of human mesenchymal stem cell (hMSC) stores by promoting the proliferation
and cytoprotection of hMSC seems to be relevant. Since these observations
suggest a role for GLP-1 during developmental processes, the aim
of the present work was to characterize GLP-1 in early development
as well as its gene targets in mouse embryonic stem (mES) cells.
Mouse embryos E6, E8, and E10.5 and pluripotent mES were used for
the inmunodetection of GLP-1 and GLP-1 receptor. Quantitative real-time
PCR was used to determine the expression levels of GLP-1R in several
tissues from E12.5 mouse embryos. Additionally, GLP-1 gene targets
were studied in mES by multiple gene expression analyses. GLP-1 and
its receptors were identified in mES and during embryonic development.
In pluripotent mES, GLP-1 modified the expression of endodermal,
ectodermal, and mesodermal gene markers as well as sonic hedgehog,
noggin, members of the fibroblast and hepatic growth factor families,
and others involved in pancreatic development. Additionally, GLP-1
promoted the expression of the antiapoptotic gene bcl2 and at the
same time reduced proapoptotic caspase genes. Our results indicate
that apart from the effects and therapeutic benefits of GLP-1 in
adulthood, it may have additional gene targets in mES cells during
embryonic life. Furthermore, the pathophysiological implications
of GLP-1 imbalance in adulthood may have a counterpart during development.},
doi = {10.1152/ajpendo.00116.2011},
eprint = {http://ajpendo.physiology.org/cgi/reprint/301/3/E494.pdf},
url = {http://ajpendo.physiology.org/cgi/content/abstract/301/3/E494}
}
@ARTICLE{Sanz2009,
author = {Sanz, Elisenda and Yang, Linghai and Su, Thomas and Morris, David
R. and McKnight, G. Stanley and Amieux, Paul S.},
title = {Cell-type-specific isolation of ribosome-associated mRNA from complex
tissues},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {13939--13944},
number = {33},
month = aug,
abstract = {Gene profiling techniques allow the assay of transcripts from organs,
tissues, and cells with an unprecedented level of coverage. However,
most of these approaches are still limited by the fact that organs
and tissues are composed of multiple cell types that are each unique
in their patterns of gene expression. To identify the transcriptome
from a single cell type in a complex tissue, investigators have relied
upon physical methods to separate cell types or in situ hybridization
and immunohistochemistry. Here, we describe a strategy to rapidly
and efficiently isolate ribosome-associated mRNA transcripts from
any cell type in vivo. We have created a mouse line, called RiboTag,
which carries an Rpl22 allele with a floxed wild-type C-terminal
exon followed by an identical C-terminal exon that has three copies
of the hemagglutinin (HA) epitope inserted before the stop codon.
When the RiboTag mouse is crossed to a cell-type-specific Cre recombinase-expressing
mouse, Cre recombinase activates the expression of epitope-tagged
ribosomal protein RPL22HA, which is incorporated into actively translating
polyribosomes. Immunoprecipitation of polysomes with a monoclonal
antibody against HA yields ribosome-associated mRNA transcripts from
specific cell types. We demonstrate the application of this technique
in brain using neuron-specific Cre recombinase-expressing mice and
in testis using a Sertoli cell Cre recombinase-expressing mouse.},
url = {http://www.pnas.org/cgi/content/abstract/106/33/13939}
}
@ARTICLE{Sanz-Santos2011,
author = {Sanz-Santos, Gema and Jimenez-Marin, Angeles and Bautista, Rocio
and Fernandez, Noe and Claros, Gonzalo and Garrido, Juan},
title = {Gene expression pattern in swine neutrophils after lipopolysaccharide
exposure: a time course comparison},
journal = {BMC Proceedings},
year = {2011},
volume = {5},
pages = {S11},
number = {Suppl 4},
abstract = {BACKGROUND:Experimental exposure of swine neutrophils to bacterial
lipopolysaccharide (LPS) represents a model to study the innate immune
response during bacterial infection. Neutrophils can effectively
limit the infection by secreting lipid mediators, antimicrobial molecules
and a combination of reactive oxygen species (ROS) without new synthesis
of proteins. However, it is known that neutrophils can modify the
gene expression after LPS exposure. We performed microarray gene
expression analysis in order to elucidate the less known transcriptional
response of neutrophils during infection.METHODS:Blood samples were
collected from four healthy Iberian pigs and neutrophils were isolated
and incubated during 6, 9 and 18 hrs in presence or absence of lipopolysaccharide
(LPS) from Salmonella enterica serovar Typhimurium. RNA was isolated
and hybridized to Affymetrix Porcine GeneChip(R). Microarray data
were normalized using Robust Microarray Analysis (RMA) and then,
differential expression was obtained by an analysis of variance (ANOVA).RESULTS:ANOVA
data analysis showed that the number of differentially expressed
genes (DEG) after LPS treatment vary with time. The highest transcriptional
response occurred at 9 hr post LPS stimulation with 1494 DEG whereas
at 6 and 18 hr showed 125 and 108 DEG, respectively. Three different
gene expression tendencies were observed: genes in cluster 1 showed
a tendency toward up-regulation; cluster 2 genes showing a tendency
for down-regulation at 9 hr; and cluster 3 genes were up-regulated
at 9 hr post LPS stimulation. Ingenuity Pathway Analysis revealed
a delay of neutrophil apoptosis at 9 hr. Many genes controlling biological
functions were altered with time including those controlling metabolism
and cell organization, ubiquitination, adhesion, movement or inflammatory
response.CONCLUSIONS:LPS stimulation alters the transcriptional pattern
in neutrophils and the present results show that the robust transcriptional
potential of neutrophils under infection conditions, indicating that
active regulation of gene expression plays a major role in the neutrophil-mediated-
innate immune response.},
doi = {10.1186/1753-6561-5-S4-S11},
issn = {1753-6561},
url = {http://www.biomedcentral.com/1753-6561/5/S4/S11}
}
@ARTICLE{Sapet2006,
author = {Sapet, Cedric and Simoncini, Stephanie and Loriod, Beatrice and Puthier,
Denis and Sampol, Jose and Nguyen, Catherine and Dignat-George, Francoise
and Anfosso, Francine},
title = {Thrombin-induced endothelial microparticle generation: identification
of a novel pathway involving ROCK-II activation by caspase-2},
journal = {Blood},
year = {2006},
volume = {108},
pages = {1868--1876},
number = {6},
month = sep,
abstract = {Thrombin exerts pleiotropic effects on endothelial cells, including
the release of microparticles (EMPs) that disseminate and exchange
information with vascular cells. Nevertheless, the mechanisms leading
to their generation are not elucidated. We performed microarray analysis
to identify genes involved in EMP release by the endothelial cell
line HMEC-1 in response to thrombin. We identified a group of genes
linked to the cytoskeleton reorganization family. Among these, the
Rho-kinase ROCK-II presented a high transcription rate. ROCK-I, another
Rho-kinase isoform, was not modulated by thrombin. Pharmacologic
inhibition of Rho-kinases or specific depletion of ROCK-II by short
interfering (si) RNA inhibited thrombin-induced EMP release. In contrast,
ROCK-I mRNA silencing did not modify EMP generation by thrombin.
Exposure of HMEC-1 to thrombin in presence of the caspase-2 selective
inhibitor Z-VDVAD-FMK prevented ROCK-II cleavage and inhibited the
thrombin-induced EMP release. These events were observed in absence
of cell death. Our data clearly identified ROCK-II as a target of
thrombin in EMP generation. They indicated that the 2 Rho-kinases
did not share identical functions. The involvement of caspase-2 in
ROCK-II activation independently of cell death points out a novel
signaling pathway that emphasizes the proteolytic activity of caspase
in EMP generation in response to cell activation.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/108/6/1868}
}
@ARTICLE{Sapkota2008,
author = {Sapkota, Dipak and Bruland, Ove and Bøe, Olav E. and Bakeer, Hala
and Elgindi, Osman A. A. and Vasstrand, Endre N. and Ibrahim, Salah
O.},
title = {Expression profile of the S100 gene family members in oral squamous
cell carcinomas},
journal = {Journal of Oral Pathology \& Medicine},
year = {2008},
volume = {37},
pages = {607--615},
number = {10},
abstract = {Background:  Several of the S100 gene members have been reported
to be differentially expressed in many human pathological conditions,
in particular, the malignancies. Identification and quantification
of the differentially expressed S100 gene members in oral squamous
cell carcinoma (OSCC) might facilitate their use as potential diagnostic
and/or prognostic markers or targets for therapy. Methods:  we
examined the expression profile of 16 members of the S100 gene family
at the mRNA level by semiquantitative reverse transcription-polymerase
chain reaction (sRT-PCR) in 27 cases of OSCCs/their pair-wised normal
controls obtained from Sudanese patients, and confirmed the sRT-PCR
results by performing quantitative real time-polymerase chain reaction
(qRT-PCR) for 6 of the 16 genes examined. Results:  With sRT-PCR,
4 (25%; S100A4, S100A6, S100A8, S100A14) out of the 16 S100 gene
members examined were found to be significantly down-regulated (PÂ <Â 0.05)
in the tumors compared to the normal controls. None of the S100 gene
members examined were found to be significantly up-regulated in the
tumors. qRT-PCR results confirmed the significant down-regulation
of the S100A4, S100A6, and S100A14 genes in the tumors examined.
Conclusion:  S100 gene family members might play an important role
in the pathogenesis of the OSCCs examined. Findings of the present
work warrant in-depth studies of the S100 gene family members, in
particular, the S100A4, S100A6, S100A8, and S100A14 to further understand
their possible role(s) in OSCC tumorigenesis.},
issn = {1600-0714},
keywords = {down-regulation, oral squamous cell carcinomas, RT-PCR, S100, Sudan},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0714.2008.00683.x}
}
@ARTICLE{Sar2009,
author = {van der Sar, Astrid M. and Spaink, Herman P. and Zakrzewska, Anna
and Bitter, Wilbert and Meijer, Annemarie H.},
title = {Specificity of the zebrafish host transcriptome response to acute
and chronic mycobacterial infection and the role of innate and adaptive
immune components},
journal = {Molecular Immunology},
year = {2009},
volume = {46},
pages = {2317--2332},
number = {11-12},
month = jul,
abstract = {Pathogenic mycobacteria have the ability to survive within macrophages
and persist inside granulomas. The complex host-pathogen interactions
that determine the outcome of a mycobacterial infection process result
in marked alterations of the host gene expression profile. Here we
used the zebrafish model to investigate the specificity of the host
response to infections with two mycobacterium strains that give distinct
disease outcomes: an acute disease with early lethality or a chronic
disease with granuloma formation, caused by Mycobacterium marinum
strains Mma20 and E11, respectively. We performed a microarray study
of different stages of disease progression in adult zebrafish and
found that the acute and the chronic strains evoked partially overlapping
host transcriptome signatures, despite that they induce profoundly
different disease phenotypes. Both strains affected many signaling
cascades, including WNT and TLR pathways. Interestingly, the strongest
differences were observed at the initial stage of the disease. The
immediate response to the acute strain was characterized by higher
expression of genes encoding MHC class I proteins, matrix metalloproteinases,
transcription factors, cytokines and other common immune response
proteins. In contrast, small GTPase and histone gene groups showed
higher expression in response to the chronic strain. We also found
that nearly 1000 mycobacterium-responsive genes overlapped between
the expression signatures of infected zebrafish adults and embryos
at different stages of granuloma formation. Since adult zebrafish
possess an adaptive immune system similar to mammals and zebrafish
embryos rely solely on innate immunity, this overlap indicates a
major contribution of the innate component of the immune system in
the response to mycobacterial infection. Taken together, our comparison
of the transcriptome responses involved in acute versus chronic infections
and in the embryonic versus adult situation provides important new
leads for investigating the mechanism of mycobacterial pathogenesis.},
issn = {0161-5890},
keywords = {Tuberculosis, Microarray, TLR, WNT, Matrix metalloproteinases, Small
GTPase signaling, MHC class I},
url = {http://www.sciencedirect.com/science/article/B6T9R-4W75RM2-1/2/ff4e07694bb2d48a373f981aed1288b5}
}
@ARTICLE{Saravanamuthu2011,
author = {Senthil S. Saravanamuthu and Tien T. Le and Chun Y. Gao and Radu
I. Cojocaru and Pushpa Pandiyan and Chunqiao Liu and Jun Zhang and
Peggy S. Zelenka and Nadean L. Brown},
title = {Conditional ablation of the Notch2 receptor in the ocular lens},
journal = {Developmental Biology},
year = {2011},
pages = { - },
number = {0},
abstract = {Notch signaling is essential for proper lens development, however
the specific requirements of individual Notch receptors have not
been investigated. Here we report the lens phenotypes of Notch2 conditionally
mutant mice, which exhibited severe microphthalmia, reduced pupillary
openings, disrupted fiber cell morphology, eventual loss of the anterior
epithelium, fiber cell dysgenesis, denucleation defects, and cataracts.
Notch2 mutants also had persistent lens stalks as early as E11.5,
and aberrant DNA synthesis in the fiber cell compartment by E14.5.
Gene expression analyses showed that upon loss of Notch2, there were
elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2
(CyclinD2), and Trp63 (p63) that negatively regulates Wnt signaling,
plus down-regulation of Cdh1 (E-Cadherin). Removal of Notch2 also
resulted in an increased proportion of fiber cells, as was found
in Rbpj and Jag1 conditional mutant lenses. However, Notch2 is not
required for AEL proliferation, suggesting that a different receptor
regulates this process. We found that Notch2 normally blocks lens
progenitor cell death. Overall, we conclude that Notch2-mediated
signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal,
and secondary fiber cell differentiation.},
doi = {10.1016/j.ydbio.2011.11.011},
issn = {0012-1606},
keywords = {Notch2},
url = {http://www.sciencedirect.com/science/article/pii/S0012160611013935}
}
@ARTICLE{Saravanan2010,
author = {Saravanan, Chandrassegar and Cao, Zhiyi and Head, Steven R and Panjwani,
Noorjahan},
title = {Analysis of differential expression of glycosyltransferases in healing
corneas by glycogene microarrays},
journal = {Glycobiology},
year = {2010},
volume = {20},
pages = {13--23},
number = {1},
month = jan,
abstract = {It is generally accepted that the glycans on the cell surface and
extracellular matrix proteins play a pivotal role in the events that
mediate re-epithelialization of wounds. Yet, the global alteration
in the structure and composition of glycans, specifically occuring
during corneal wound closure remains unknown. In this study, GLYCOv2
glycogene microarray technology was used for the first time to identify
the differentially expressed glycosylation-related genes in healing
mouse corneas. Of [~]2000 glycogenes on the array, the expression
of 11 glycosytransferase and glycosidase enzymes was upregulated
and that of 19 was downregulated more than 1.5-fold in healing corneas
compared with the normal, uninjured corneas. Among them, notably,
glycosyltransferases, {beta}3GalT5, T-synthase, and GnTIVb, were
all found to be induced in the corneas in response to injury, whereas,
GnTIII and many sialyltransferases were downregulated. Interestingly,
it appears that the glycan structures on glycoproteins and glycolipids,
expressed in healing corneas as a result of differential regulation
of these glycosyltransferases, may serve as specific counter-receptors
for galectin-3, a carbohydrate-binding protein, known to play a key
role in re-epithelialization of corneal wounds. Additionally, many
glycogenes including a proteoglycan, glypican-3, cell adhesion proteins
dectin-1 and -2, and mincle, and mucin 1 were identified for the
first time to be differentially regulated during corneal wound healing.
Results of glycogene microarray data were confirmed by qRT-PCR and
lectin blot analyses. The differentially expressed glycogenes identified
in the present study have not previously been investigated in the
context of wound healing and represent novel factors for investigating
the role of carbohydrate-mediated recognition in corneal wound healing.},
url = {http://glycob.oxfordjournals.org/cgi/content/abstract/20/1/13}
}
@ARTICLE{Saravanan2009,
author = {Saravanan, Chandrassegar and Cao, Zhiyi and Head, Steven R. and Panjwani,
Noorjahan},
title = {Detection of Differentially Expressed Wound-Healing-Related Glycogenes
in Galectin-3-Deficient Mice},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {5690--5696},
number = {12},
month = dec,
abstract = {Purpose.A prior study showed that exogenous galectin-3 (Gal-3) stimulates
re-epithelialization of corneal wounds in wild-type (Gal-3+/+) mice
but, surprisingly, not in galectin-3-deficient (Gal-3-/-) mice. In
an effort to understand why the injured corneas of Gal-3-/- mice
are unresponsive to exogenous Gal-3, the present study was designed
to determine whether genes encoding the enzymes that regulate the
synthesis of glycan ligands of Gal-3 are differentially expressed
in Gal-3-/- corneas compared with the Gal-3+/+ corneas. Methods.Glycogene
microarray technology was used to identify differentially expressed
glycosyltransferases in healing Gal-3+/+ and Gal-3-/- corneas. Results.Of
[~]2000 glycogenes on the array, the expression of 8 was upregulated
and that of 14 was downregulated more than 1.3-fold in healing Gal-3-/-
corneas. A galactosyltransferase, {beta}3GalT5, which has the ability
to synthesize Gal-3 ligands was markedly downregulated in healing
Gal-3-/- corneas. The genes for polypeptide galactosaminyltransferases
(ppGalNAcT-3 and -7) that are known to initiate O-linked glycosylation
and N-aspartyl-{beta}-glucosaminidase, which participates in the
removal of N-glycans, were found to be upregulated in healing Gal-3-/-
corneas. Microarray data were validated by qRT-PCR. Conclusions.Based
on the known functions of the differentially expressed glycogenes,
it appears that the glycan structures on glycoproteins and glycolipids,
synthesized as a result of the differential glycogene expression
pattern in healing Gal-3-/- corneas may lead to the downregulation
of specific counterreceptors for Gal-3. This may explain, at least
in part, why, unlike healing Gal-3+/+ corneas, the healing Gal-3-/-
corneas are unresponsive to the stimulatory effect of exogenous Gal-3
on re-epithelialization of corneal wounds.},
url = {http://www.iovs.org/cgi/content/abstract/50/12/5690}
}
@ARTICLE{Sargeant2010,
author = {Sargeant, Hannah R. and McDowall, Kenneth J. and Miller, Helen M.
and Shaw, Marie-Anne},
title = {Dietary zinc oxide affects the expression of genes associated with
inflammation: Transcriptome analysis in piglets challenged with ETEC
K88},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {137},
pages = {120--129},
number = {1-2},
month = sep,
abstract = {The post-weaning growth check in commercial pig production systems
is often associated with gastrointestinal infection, in particular
that caused by enterotoxigenic Escherichia coli (ETEC) K88. Pharmacological
doses of zinc oxide (ZnO) in the post-weaning diet reduce the incidence
of diarrhoea and improve piglet performance. In the present study,
piglets reared indoors or outdoors and weaned onto diets with or
without pharmacological levels of ZnO were orally challenged with
ETEC K88. Quantitative real-time PCR was performed on RNA extracted
from jejunal lamina propria and Peyer's patch samples, to compare
expression of a variety of candidate genes between treatments. Candidate
genes were selected from an initial microarray study using pooled
RNA to identify differentially expressed genes. Dietary treatment
with ZnO was associated with significant differences in the transcript
abundance of several genes. Zinc supplementation was associated with
a marked decrease in expression of immune response genes concerned
with inflammation, and possibly related to the stage of infection.
Interestingly, evidence was also obtained that a reduced level of
MUC4 (a proposed ETEC K88 receptor) was associated with zinc supplementation
suggesting a mechanism that might influence ETEC infection. These
findings indicate that zinc oxide supplementation may reduce the
level of inflammation caused by ETEC challenge.},
issn = {0165-2427},
keywords = {Porcine post-weaning performance, Small intestine, Zinc oxide, Pre-weaning
outdoor rearing, ETEC K88, Inflammation, Genomics},
url = {http://www.sciencedirect.com/science/article/B6TD5-502V6NY-1/2/5a950b02bb015365150f69ef305fc9e1}
}
@ARTICLE{Sariol2007,
author = {Sariol, Carlos A. and Munoz-Jordan, Jorge L. and Abel, Kristina and
Rosado, Lymarie C. and Pantoja, Petraleigh and Giavedoni, Luis and
Rodriguez, Idia Vanessa and White, Laura J. and Martinez, Melween
and Arana, Teresa and Kraiselburd, Edmundo N.},
title = {Transcriptional Activation of Interferon-Stimulated Genes but Not
of Cytokine Genes after Primary Infection of Rhesus Macaques with
Dengue Virus Type 1},
journal = {Clin. Vaccine Immunol.},
year = {2007},
volume = {14},
pages = {756--766},
number = {6},
month = jun,
abstract = {Macaques are the only animal model used to test dengue virus (DENV)
vaccine candidates. Nevertheless, the pathogenesis of DENV in macaques
is not well understood. In this work, by using Affymetrix oligonucleotide
microarrays, we studied the broad transcriptional modifications and
cytokine expression profile after infecting rhesus macaques with
DENV serotype 1. Five days after infection, these animals produced
a potent, innate antiviral immune response by inducing the transcription
of signature genes from the interferon (IFN) pathway with demonstrated
antiviral activity, such as myxoprotein, 2',5'-oligoadenylate synthetase,
phospholipid scramblase 1, and viperin. Also, IFN regulatory element
7, IFN-stimulated gene 15, and protein ligases linked to the ISGylation
process were up-regulated. Unexpectedly, no up-regulation of IFN-{alpha},
-{beta}, or -{gamma} genes was detected. Transcription of the genes
of interleukin-10 (IL-10), IL-8, IL-6, and tumor necrosis factor
alpha was neither up-regulated nor down-regulated. Results were confirmed
by real-time PCR and by multiplex cytokine detection in serum samples.},
url = {http://cvi.asm.org/cgi/content/abstract/14/6/756}
}
@ARTICLE{Saris2009,
author = {Saris, Christiaan and Horvath, Steve and van Vught, Paul and van
Es, Michael and Blauw, Hylke and Fuller, Tova and Langfelder, Peter
and DeYoung, Joseph and Wokke, John and Veldink, Jan and van den
Berg, Leonard and Ophoff, Roel},
title = {Weighted gene co-expression network analysis of the peripheral blood
from Amyotrophic Lateral Sclerosis patients},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {405},
number = {1},
abstract = {BACKGROUND:Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder
characterized by progressive degeneration of motor neurons in the
brain and spinal cord. Diagnosis is mainly based on clinical symptoms,
and there is currently no therapy to stop the disease or slow its
progression. Since access to spinal cord tissue is not possible at
disease onset, we investigated changes in gene expression profiles
in whole blood of ALS patients.RESULTS:Our transcriptional study
showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%)
showed significant differential expression in a discovery dataset
consisting of 30 ALS patients and 30 healthy controls. Weighted gene
co-expression network analysis (WGCNA) was used to find disease-related
networks (modules) and disease related hub genes. Two large co-expression
modules were found to be associated with ALS. Our findings were replicated
in a second (30 patients and 30 controls) and third dataset (63 patients
and 63 controls), thereby demonstrating a highly significant and
consistent association of two large co-expression modules with ALS
disease status. Ingenuity Pathway Analysis of the ALS related module
genes implicates enrichment of functional categories related to genetic
disorders, neurodegeneration of the nervous system and inflammatory
disease. The ALS related modules contain a number of candidate genes
possibly involved in pathogenesis of ALS.CONCLUSION:This first large-scale
blood gene expression study in ALS observed distinct patterns between
cases and controls which may provide opportunities for biomarker
development as well as new insights into the molecular mechanisms
of the disease.},
doi = {10.1186/1471-2164-10-405},
issn = {1471-2164},
pubmedid = {19712483},
url = {http://www.biomedcentral.com/1471-2164/10/405}
}
@ARTICLE{Saris2006,
author = {Saris, Jasper J. and 't Hoen, Peter A.C. and Garrelds, Ingrid M.
and Dekkers, Dick H.W. and den Dunnen, Johan T. and Lamers, Jos M.J.
and Jan Danser, A.H.},
title = {Prorenin Induces Intracellular Signaling in Cardiomyocytes Independently
of Angiotensin II},
journal = {Hypertension},
year = {2006},
volume = {48},
pages = {564--571},
number = {4},
month = oct,
abstract = {Tissue accumulation of circulating prorenin results in angiotensin
generation, but could also, through binding to the recently cloned
(pro)renin receptor, lead to angiotensin-independent effects, like
p42/p44 mitogen-activated protein kinase (MAPK) activation and plasminogen-activator
inhibitor (PAI)-1 release. Here we investigated whether prorenin
exerts angiotensin-independent effects in neonatal rat cardiomyocytes.
Polyclonal antibodies detected the (pro)renin receptor in these cells.
Prorenin affected neither p42/p44 MAPK nor PAI-1. PAI-1 release did
occur during coincubation with angiotensinogen, suggesting that this
effect is angiotensin mediated. Prorenin concentration-dependently
activated p38 MAPK and simultaneously phosphorylated HSP27. The latter
phosphorylation was blocked by the p38 MAPK inhibitor SB203580. Rat
microarray gene (n=4800) transcription profiling of myocytes stimulated
with prorenin detected 260 regulated genes (P<0.001 versus control),
among which genes downstream of p38 MAPK and HSP27 involved in actin
filament dynamics and (cis-)regulated genes confined in blood pressure
and diabetes QTL regions, like Syntaxin-7, were overrepresented.
Quantitative real-time RT-PCR of 7 selected genes (Opg, Timp1, Best5,
Hsp27, pro-Anp, Col3a1, and Hk2) revealed temporal regulation, with
peak levels occurring after 4 hours of prorenin exposure. This regulation
was not altered in the presence of the renin inhibitor aliskiren
or the angiotensin II type 1 receptor antagonist eprosartan. Finally,
pilot 2D proteomic differential display experiments revealed actin
cytoskeleton changes in cardiomyocytes after 48 hours of prorenin
stimulation. In conclusion, prorenin exerts angiotensin-independent
effects in cardiomyocytes. Prorenin-induced stimulation of the p38
MAPK/HSP27 pathway, resulting in alterations in actin filament dynamics,
may underlie the severe cardiac hypertrophy that has been described
previously in rats with hepatic prorenin overexpression.},
url = {http://hyper.ahajournals.org/cgi/content/abstract/48/4/564}
}
@ARTICLE{Sarkar2011,
author = {Sarkar, M and Schilffarth, S and Schams, D and Meyer, HHD and Berisha,
B},
title = {The Expression of Thrombopoietin and its Receptor During Different
Physiological Stages in the Bovine Ovary},
journal = {Reproduction in Domestic Animals},
year = {2011},
volume = {46},
pages = {757--762},
number = {5},
abstract = {Thrombopoietin (TPO) is known to be involved in megakaryocytopoiesis,
but its role in the control of ovarian function is unknown in cattle.
The aims of this study were to demonstrate the expression of TPO
and its receptor (c-MPL) in detail in bovine corpus luteum (CL) obtained
from different stages of the oestrous cycle and during pregnancy
– and to demonstrate that TPO/c-MPL system is expressed clearly
in bovine follicles. Real-time RT-PCR (qPCR) and ELISA were applied
to investigate mRNA expression of examined factors and TPO protein,
respectively. In this investigation, increases in the concentrations
of TPO protein and the mRNA expression of TPO and c-MPL were noticed
during both early luteal stage and late luteal stage of the oestrous
cycle. Furthermore, the expression of TPO/c-MPL system does not show
any significant regulation in the CL throughout pregnancy. Highest
co-expression of TPO/c-MPL system in both theca interna (TI) and
granulosa cells (GC) in small follicles (<10Â mm in diameter) was
observed in this study that may suggest the possible role of TPO/c-MPL
system in proliferation of TI and GC cells. To conclude, the results
demonstrate the possible involvement of locally produced TPO/c-MPL
system as a ‘physiological filter’ in bovine ovary where they
may promote cell selection by inducing proliferation of viable cells
and scavenging non-viable cells and thereby may play an important
role in modulation of ovarian function.},
doi = {10.1111/j.1439-0531.2010.01736.x},
issn = {1439-0531},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0531.2010.01736.x}
}
@ARTICLE{Sarkar2007,
author = {Sarkar, Suparna A. and Wong, Randall and Hackl, Seija I. and Moua,
Ong and Gill, Ronald G. and Wiseman, Alexander and Davidson, Howard
W. and Hutton, John C.},
title = {Induction of Indoleamine 2,3-Dioxygenase by Interferon-{gamma} in
Human Islets},
journal = {Diabetes},
year = {2007},
volume = {56},
pages = {72--79},
number = {1},
month = jan,
abstract = {Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial, rate-limiting
step of tryptophan (Trp) catabolism along the kynurenine (KYN) pathway,
and its induction in cells of the immune system in response to cytokines
has been implicated in the regulation of antigen presentation and
responses to cell-mediated immune attack. Microarray and quantitative
PCR analyses of isolated human islets incubated with interferon (IFN)-{gamma}
for 24 h revealed increased expression of IDO mRNA (>139-fold) and
Trp-tRNA synthase (WARS) (>17-fold) along with 975 other transcripts
more than threefold, notably the downstream effectors janus kinase
(JAK)2, signal transducer and activator of transcription (STAT)1,
IFN-{gamma} regulatory factor-1, and several chemokines (CXCL9/MIG,
CXCL10/IP10, CXCL11/1-TAC, CCL2, and CCL5/RANTES) and their receptors.
IDO protein expression was upregulated in IFN-{gamma}-treated islets
and accompanied by increased intracellular IDO enzyme activity and
the release of KYN into the media. The response to IFN-{gamma} was
countered by interleukin-4 and 1{alpha}-methyl Trp. Immunohistochemical
localization showed IDO to be induced in cells of both endocrine,
including pancreatic duodenal homeobox 1-positive {beta}-cells, and
nonendocrine origin. We postulate that in the short term, IDO activation
may protect islets from cytotoxic damage, although chronic exposure
to various Trp metabolites could equally lead to {beta}-cell attrition.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/56/1/72}
}
@ARTICLE{Sarmento2008,
author = {Sarmento, Luciana and Afonso, Claudio L. and Estevez, Carlos and
Wasilenko, Jamie and Pantin-Jackwood, Mary},
title = {Differential host gene expression in cells infected with highly pathogenic
H5N1 avian influenza viruses},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {125},
pages = {291--302},
number = {3-4},
month = oct,
abstract = {In order to understand the molecular mechanisms by which different
strains of avian influenza viruses overcome host response in birds,
we used a complete chicken genome microarray to compare early gene
expression levels in chicken embryo fibroblasts (CEF) infected with
two avian influenza viruses (AIV), A/CK/Hong Kong/220/97 and A/Egret/Hong
Kong/757.2/02, with different replication characteristics. Gene ontology
revealed that the genes with altered expression are involved in many
vital functional classes including protein metabolism, translation,
transcription, host defense/immune response, ubiquitination and the
cell cycle. Among the immune-related genes, MEK2, MHC class I, PDCD10
and Bcl-3 were selected for further expression analysis at 24 hpi
using semi-quantitive RT-PCR. Infection of CEF with A/Egret/Hong
Kong/757.2/02 resulted in a marked repression of MEK2 and MHC class
I gene expression levels. Infection of CEF with A/CK/Hong Kong/220/97
induced an increase of MEK2 and a decrease in PDCD10 and Bcl-3 expression
levels. The expression levels of alpha interferon (IFN-[alpha]),
myxovirus resistance 1 (Mx1) and interleukin-8 (IL-8) were also analyzed
at 24 hpi, showing higher expression levels of all of these genes
after infection with A/CK/Hong Kong/220/97 compared to A/Egret/Hong
Kong/757.2/02. In addition, comparison of the NS1 sequences of the
viruses revealed amino acid differences that may explain in part
the differences in IFN-[alpha] expression observed. Microarray gene
expression analysis has proven to be a useful tool on providing important
insights into how different AIVs affect host gene expression and
how AIVs may use different strategies to evade host response and
replicate in host cells.},
issn = {0165-2427},
keywords = {Avian influenza virus, Gene expression, Immune response, Chicken embryo
fibroblasts},
url = {http://www.sciencedirect.com/science/article/B6TD5-4SNGM1C-1/2/c239f36d7cfb855192c99f95c00c350e}
}
@ARTICLE{Sarosiek2010,
author = {Sarosiek, Kristopher A. and Malumbres, Raquel and Nechushtan, Hovav
and Gentles, Andrew J. and Avisar, Eli and Lossos, Izidore S.},
title = {Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis
of diffuse large B-cell lymphomas},
journal = {Blood},
year = {2010},
volume = {115},
pages = {570--580},
number = {3},
month = jan,
abstract = {Interleukin-21 (IL-21), a member of the IL-2 cytokine family, has
diverse regulatory effects on natural killer (NK), T, and B cells.
In contrast to other cytokines that are usually immunostimulatory,
IL-21 can induce apoptosis of murine B cells at specific activation-differentiation
stages. This effect may be used for treatment of B-cell malignancies.
Herein we report that diffuse large B-cell lymphoma (DLBCL) cell
lines exhibit widespread expression of the IL-21 receptor (IL-21R)
and that IL-21 stimulation leads to cell-cycle arrest and caspase-dependent
apoptosis. IL-21 also induces apoptosis in de novo DLBCL primary
tumors but does not affect viability of human healthy B cells. Furthermore,
IL-21 promotes tumor regression and prolongs survival of mice harboring
xenograft DLBCL tumors. The antilymphoma effects of this cytokine
are dependent on a mechanism involving IL-21-activated signal transducer
and activator of transcription 3 (STAT3) up-regulating expression
of c-Myc. This up-regulation promotes a decrease in expression of
antiapoptotic Bcl-2 and Bcl-XL proteins triggering cell death. Our
results represent one of the first examples in which the STAT3-c-Myc
signaling pathway, which can promote survival and oncogenesis, can
induce apoptosis in neoplastic cells. Moreover, based on IL-21's
potency in vitro and in animal models, our findings indicate that
this cytokine should be examined in clinical studies of DLBCL.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/3/570}
}
@ARTICLE{Sarov-Blat2007,
author = {Sarov-Blat, Lea and Kiss, Robert S. and Haidar, Bassam and Kavaslar,
Nihan and Jaye, Michael and Bertiaux, Melissa and Steplewski, Klaudia
and Hurle, Mark R. and Sprecher, Dennis and McPherson, Ruth and Marcel,
Yves L.},
title = {Predominance of a Proinflammatory Phenotype in Monocyte-Derived Macrophages
From Subjects With Low Plasma HDL-Cholesterol},
journal = {Arterioscler Thromb Vasc Biol},
year = {2007},
volume = {27},
pages = {1115--1122},
number = {5},
month = may,
abstract = {Objective-- Reduced plasma concentrations of high-density lipoprotein-cholesterol
(HDL-C) are a significant risk factor for cardiovascular disease.
Mechanisms that regulate HDL-C concentrations represent an important
area of investigation. Methods and Results-- Comparative transcriptome
analyses of monocyte-derived macrophages (MDM) from a large population
of low HDL-C subjects and age- and sex-matched controls revealed
a cluster of inflammatory genes highly expressed in low HDL-C subjects.
The expression levels of peroxisome proliferator activated receptor
(PPAR) {gamma} and several antioxidant metallothionein genes were
decreased in MDM from all low HDL-C groups compared with controls,
as was the expression of other genes regulated by PPAR{gamma}, including
CD36, adipocyte fatty acid binding protein (FABP4), and adipophilin
(ADFP). In contrast, PPAR{delta} expression was increased in MDM
from low HDL-C groups. Quantitative RT-PCR corroborated all major
findings from the microarray analysis in two separate patient cohorts.
Expression of several inflammatory cytokine genes including interleukin
1{beta}, interleukin 8, and tumor necrosis factor {alpha} were highly
increased in low HDL-C subjects. Conclusions-- The activated proinflammatory
state of monocytes and MDM in low HDL-C subjects constitutes a novel
parameter of risk associated with HDL deficiency, related to altered
expression of metallothionein genes and the reciprocal regulation
of PPAR{gamma} and PPAR{delta}. We demonstrate that cholesterol loaded
monocyte-derived macrophages from low HDL-C subjects exhibit a complex
inflammatory gene response, related to altered expression of PPAR{gamma},
PPAR{delta}, and a cluster of metallothionein genes. Our results
suggest that a heightened macrophage inflammatory response may contribute
to the pathophysiological consequences of HDL deficiency.},
url = {http://atvb.ahajournals.org/cgi/content/abstract/27/5/1115}
}
@ARTICLE{Sarr2011,
author = {Sarr, Ousseynou and Gondret, Florence and Jamin, Agnes and Le Huerou-Luron,
Isabelle and Louveau, Isabelle},
title = {A high-protein neonatal formula induces a temporary reduction of
adiposity and changes later adipocyte physiology},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {300},
pages = {R387--397},
number = {2},
month = feb,
abstract = {The high-protein content of formula offered to low-birth weight babies
is suspected to increase the risk of obesity later in life. This
study assesses the immediate and subsequent effects of a protein
intake in excess during suckling on hormonal and metabolic status
and adipose tissue features in a porcine model of intrauterine growth
restriction. Piglets were fed milk replacers formulated to provide
an adequate (AP) or a high (HP) protein supply from day 2 to day
28. A subset of piglets was killed at day 28. After weaning, the
remaining piglets had free access to the same solid high-fat diet
until day 160. From day 2 to day 28, HP piglets had a greater daily
weight gain (P < 0.05). Relative weight of perirenal adipose tissue
(PAT), adipocyte mean diameters, activities of lipogenic enzymes
in PAT and subcutaneous adipose tissue (SCAT), and leptinemia were
lower (P < 0.05) in HP piglets than in AP piglets. Genes related
to glucose utilization and lipid anabolism in PAT and SCAT were (P
< 0.05) or tended (P < 0.1) to be downregulated in HP piglets. At
day 160, adipocytes were enlarged, whereas lipogenic rates in adipocytes
were reduced (P < 0.05) in SCAT of HP compared with AP pigs. Percent
body fat, mRNA levels of genes controlling lipid metabolism, and
plasma concentrations of hormones and metabolites were similar in
HP and AP pigs. In conclusion, a HP neonatal formula induced a temporary
reduction of adiposity and changed adipocyte physiology at peripubertal
age.},
comment = {10.1152/ajpregu.00459.2010},
url = {http://ajpregu.physiology.org/cgi/content/abstract/300/2/R387}
}
@ARTICLE{Sarr2012,
author = {Ousseynou Sarr and Isabelle Louveau and Isabelle Le Huërou-Luron
and Florence Gondret},
title = {Adipose tissue proteomes of intrauterine growth-restricted piglets
artificially reared on a high-protein neonatal formula},
journal = {The Journal of Nutritional Biochemistry},
year = {2012},
pages = { - },
number = {0},
abstract = {The eventuality that adipose tissues adapt to neonatal nutrition in
a way that may program later adiposity or obesity in adulthood is
receiving increasing attention in neonatology. This study assessed
the immediate effects of a high-protein neonatal formula on proteome
profiles of adipose tissues in newborn piglets with intrauterine
growth restriction. Piglets (10th percentile) were fed milk replacers
formulated to provide an adequate (AP) or a high (HP) protein supply
from day 2 to the day prior weaning (day 28, n=5 per group). Adipocytes
with small diameters were present in greater proportions in subcutaneous
and perirenal adipose tissues from HP piglets compared with AP ones
at this age. Two-dimensional gel electrophoresis analysis of adipose
tissue depots revealed a total of 32 protein spots being up- or down-regulated
(P<.10) for HP piglets compared with AP piglets; 18 of them were
unambiguously identified by mass spectrometry. These proteins were
notably related to signal transduction (annexin 2), redox status
(peroxiredoxin 6, glutathione S-transferase omega 1, cyclophilin-A),
carbohydrate metabolism (ribose-5-phosphate dehydrogenase, lactate
dehydrogenase), amino acid metabolism (glutamate dehydrogenase 1)
and cell cytoskeleton dynamics (dynactin and cofilin-1). Proteomic
changes occurred mainly in dorsal subcutaneous adipose tissue, with
the notable exception of annexin 1 involved in lipid metabolic process
having a lower abundance in HP piglets for perirenal adipose tissue
only. Together, modulation in those proteins could represent a novel
starting point for elucidating catch-up fat growth observed in later
life in growing animals having been fed HP formula.},
doi = {10.1016/j.jnutbio.2011.09.002},
issn = {0955-2863},
keywords = {Adipose tissue},
url = {http://www.sciencedirect.com/science/article/pii/S0955286311002622}
}
@ARTICLE{Sarson2009,
author = {Sarson, Aimie and Wang, Ying and Kang, Zhumei and Dowd, Scot and
Lu, Yang and Yu, Hai and Han, Yanming and Zhou, Huaijun and Gong,
Joshua},
title = {Gene expression profiling within the spleen of Clostridium perfringens-challenged
Broilers fed antibiotic-medicated and non-medicated diets},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {260},
number = {1},
abstract = {BACKGROUND:Clostridium perfringens (Cp) is a Gram-positive anaerobic
bacterium that causes necrotic enteritis (NE) in poultry when it
overgrows in the small intestine. NE disease has previously been
controlled through the use of growth-promoting antibiotics. This
practice was recently banned in European countries, leading to significantly
increased incidence of NE threatening the poultry industry. Control
strategies and technology as substitutes to dietary antibiotics are
therefore urgently required. To develop the substitutes, it is important
to understand host immune responses to Cp infection. However, the
knowledge is still lacking. We therefore investigated gene expression
profiles within immunologically-relevant tissue, the spleen, in order
to identify factors that are involved in immunity to NE and have
potential as therapeutic targets.RESULTS:Use of a 44 K Agilent chicken
genome microarray revealed significant up-regulation of many immune-associated
genes in Cp-challenged chickens, including galectin 3, IFNAR1, IgY-receptor,
TCR?, granzyme A, and mannose-6-P-R, which were subsequently validated
by quantitative PCR assays. Functional annotation of differentially
expressed genes was conducted using the High Throughput Gene Ontology
Functional Annotation database. Medicated and Non-medicated chickens
had similar annotation profiles with cell activities and regulation
being the most dominant biological processes following Cp infection.CONCLUSION:Broiler
chickens demonstrated an intricate and holistic magnitude of host
response to Cp challenge and the development of NE. Although the
influence of dietary antibiotics appeared to be less significant
than the disease process, both had a considerable impact on the host
response. Markers previously identified in intestinal inflammatory
diseases of other species, including humans, and indicators of enhanced
antibody responses, appeared to be involved in the chicken response
to Cp challenge. The significance in host immune responses of immune
mediators identified from the present study warrants further studies
to verify their functions during NE development and to determine
their potential application to control NE disease.},
doi = {10.1186/1471-2164-10-260},
issn = {1471-2164},
pubmedid = {19500416},
url = {http://www.biomedcentral.com/1471-2164/10/260}
}
@ARTICLE{Sarvari2010,
author = {Sarvari, Miklos and Hrabovszky, Erik and Kallo, Imre and Galamb,
Orsolya and Solymosi, Norbert and Liko, Istvan and Molnar, Bela and
Tihanyi, Karoly and Szombathelyi, Zsolt and Liposits, Zsolt},
title = {Gene Expression Profiling Identifies Key Estradiol Targets in the
Frontal Cortex of the Rat},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {1161--1176},
number = {3},
month = mar,
abstract = {Estradiol modulates a wide range of neural functions in the frontal
cerebral cortex where subsets of neurons express estrogen receptor-{alpha}
and -{beta}. Through these receptors, estradiol contributes to the
maintenance of normal operation of the frontal cortex. During the
decline of gonadal hormones, the frequency of neurological and psychiatric
disorders increases. To shed light on the etiology of disorders related
to declining levels of estrogens, we studied the genomic responses
to estradiol. Ovariectomized rats were treated with a sc injection
of estradiol. Twenty-four hours later, samples from the frontal cortices
were dissected, and their mRNA content was analyzed. One hundred
thirty-six estradiol-regulated transcripts were identified on Rat
230 2.0 Expression Array. Of the 136 estrogen-regulated genes, 26
and 36 genes encoded proteins involved in the regulation of transcription
and signal transduction, respectively. Thirteen genes were related
to the calcium signaling pathway. They comprised five genes coding
for neurotransmitter receptors. Transcription of three neuropeptides,
including cocaine- and amphetamine-regulated transcript, were up-regulated.
Fifty-two genes were selected for validation, and 12 transcriptional
changes were confirmed. These results provided evidence that estradiol
evokes broad transcriptional response in the cortex. Modulation of
key components of the calcium signaling pathway, dopaminergic, serotonergic,
and glutamatergic neurotransmission, may explain the influence of
estrogens on cognitive function and behavior. Up-regulation of cocaine-
and amphetamine-regulated transcript contributes to the neuroprotective
effects of estradiol. Identification of estradiol-regulated genes
in the frontal cortex helps to understand the pathomechanism of neurological
and psychiatric disorders associated with altered levels of estrogens.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/3/1161}
}
@ARTICLE{Sarvari2011,
author = {Sarvari, Miklos and Hrabovszky, Erik and Kallo, Imre and Solymosi,
Norbert and Toth, Kinga and Liko, Istvan and Szeles, Janos and Maho,
Sandor and Molnar, Bela and Liposits, Zsolt},
title = {Estrogens regulate neuroinflammatory genes via estrogen receptors
alpha and beta in the frontal cortex of middle-aged female rats},
journal = {Journal of Neuroinflammation},
year = {2011},
volume = {8},
pages = {82},
number = {1},
abstract = {BACKGROUND:Estrogens exert anti-inflammatory and neuroprotective effects
in the brain mainly via estrogen receptors alpha (ERalpha) and beta
(ERbeta). These receptors are members of the nuclear receptor superfamily
of ligand-dependent transcription factors. This study was aimed at
the elucidation of the effects of ERalpha and ERbeta agonists on
the expression of neuroinflammatory genes in the frontal cortex of
aging female rats.METHODS:To identify estrogen-responsive immunity/inflammation
genes, we treated middle-aged, ovariectomized rats with 17beta-estradiol
(E2), ERalpha agonist 16alpha-lactone-estradiol (16alpha-LE2) and
ERbeta agonist diarylpropionitrile (DPN), or vehicle by Alzet minipump
delivery for 29 days. Then we compared the transcriptomes of the
frontal cortex of estrogen-deprived versus ER agonist-treated animals
using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative
real-time PCR. Microarray and PCR data were evaluated by using Bioconductor
packages and the RealTime StatMiner software, respectively.RESULTS:Microarray
analysis revealed the transcriptional regulation of 21 immunity/inflammation
genes by 16alpha-LE2. The subsequent comparative real-time PCR study
analyzed the isotype specific effects of ER agonists on neuroinflammatory
genes of primarily glial origin. E2 regulated the expression of sixteen
genes, including down-regulation of complement C3 and C4b, Ccl2,
Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b,
Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b,
IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16alpha-LE2 and
DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation
of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b.CONCLUSIONS:These
findings provide evidence that E2, 16alpha-LE2 and DPN modulate the
expression of neuroinflammatory genes in the frontal cortex of middle-aged
female rats via both ERalpha and ERbeta. We propose that ERbeta is
a promising target to suppress regulatory functions of glial cells
in the E2-deprived female brain and in various neuroinflammatory
diseases.},
doi = {10.1186/1742-2094-8-82},
issn = {1742-2094},
pubmedid = {21774811},
url = {http://www.jneuroinflammation.com/content/8/1/82}
}
@ARTICLE{Sarvari2010a,
author = {Sarvari, Miklos and Kallo, Imre and Hrabovszky, Erik and Solymosi,
Norbert and Toth, Kinga and Liko, Istvan and Molnar, Bela and Tihanyi,
Karoly and Liposits, Zsolt},
title = {Estradiol Replacement Alters Expression of Genes Related to Neurotransmission
and Immune Surveillance in the Frontal Cortex of Middle-Aged, Ovariectomized
Rats},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {3847--3862},
number = {8},
month = aug,
abstract = {Estradiol (E2) modulates a wide range of functions of the frontal
cerebral cortex. From the onset of menopause, declining levels of
E2 can cause cognitive disturbances and changes in behavior that
can be counterbalanced by hormone replacement. To study the effect
of E2 replacement on the cortical transcriptome in a rodent model
with low serum E2 level, we treated middle-aged, ovariectomized rats
with E2 or vehicle using osmotic minipumps for 4 wk. Six animals
for each group were selected, and samples of their frontal cortex
were subjected to expression profiling using oligonucleotide microarrays.
The explored E2-regulated genes were related to neurotransmission
(Adora2a, Cartpt, Drd1a, Drd2, Gjb2, Nts, and Tac1), immunity (C3,
C4b, Cd74, Fcgr2b, Mpeg1, and RT1-Aw2), signal transduction (Igf2,
Igfbp2, Igfbp6, Rgs9, and Sncg), transport (Abca1, Hba-a2, Slc13a3,
and Slc22a8), extracellular matrix (Col1a2, Col3a1, Fmod, and Lum),
and transcription (Irf7 and Nupr1). Seventy-four percent of the transcriptional
changes identified by microarray were confirmed by quantitative real-time
PCR. The genes identified by expression profiling indicated that
chronic E2 replacement significantly altered the transcriptome of
the frontal cortex. The genomic effects of E2 influenced dopaminergic
and peptidergic neurotransmission, immune surveillance, adenosine
and insulin-like growth factor signaling and transport processes,
among other functions. Identification of these novel E2-regulated
mechanisms highlights the wide range of genomic responses of the
aging female frontal cerebral cortex subjected to hormone replacement.
Some of the genomic effects identified in this study may underlie
the beneficial effects of E2 on cognition, behavior, and neuroprotection.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/8/3847}
}
@ARTICLE{Sas2007,
author = {Sas, Filip and Begum, Murshida and Vandersmissen, Tim and Geens,
Marisa and Claeys, Ilse and Van Soest, Sofie and Huybrechts, Jurgen
and Huybrechts, Roger and De Loof, Arnold},
title = {Development of a real-time PCR assay for measurement of yellow protein
mRNA transcription in the desert locust Schistocerca gregaria: A
basis for isolation of a peptidergic regulatory factor},
journal = {Peptides},
year = {2007},
volume = {28},
pages = {38--43},
number = {1},
month = jan,
booktitle = {Invertebrate Neuropeptides VII, Invertebrate Neuropeptide Conference
2006},
issn = {0196-9781},
keywords = {Yellow protein, Phase transition, Insect endocrinology, Cuticle, Juvenile
hormone, Neuropeptides},
url = {http://www.sciencedirect.com/science/article/B6T0M-4MGVT0B-2/2/dc13cac54ecd6e4f37f989ed77bd0e79}
}
@ARTICLE{Sas2010,
author = {Sas, Kelli M. and Baatz, John E.},
title = {Brevetoxin-2 induces an inflammatory response in an alveolar macrophage
cell line},
journal = {International Journal of Hygiene and Environmental Health},
year = {2010},
volume = {213},
pages = {352--358},
number = {5},
month = sep,
abstract = {Brevetoxins, the algal toxins produced by Karenia brevis during red
tide blooms, adversely impact health following ingestion or inhalation.
Inhalation of brevetoxins results in a variety of acute symptoms
including coughing, wheezing, and shortness of breath. Analysis of
manatee lungs following death by purported brevetoxicosis has identified
brevetoxin accumulation within macrophages, with pathological manifestions
of lung congestion, inflammation, and edema. The goals of this work
were to specifically examine effects of brevetoxin-2 on alveolar
macrophages, a key cell in responding to toxins in the lung, as well
as to determine if brevetoxin-2 results in an inflammatory response
and/or direct cytotoxicity. Exposure of an alveolar macrophage cell
line (MH-S) to an environmentally and physiologically relevant dose
of brevetoxin-2 (0.5 [mu]g/ml) did not significantly alter cellular
growth over a 24 h time period. However, exposure of MH-S cells to
brevetoxin-2 for 6 h increased phagocytosis of latex beads, increased
secretion of interleukin (IL)-2, IL-4, and tumor necrosis factor-[alpha],
and decreased secretion of IL-5. Very few changes were seen in gene
expression following 3 or 6 h exposure to brevetoxin-2. These results
show that brevetoxin-2 induced an immune response indicative of inflammation
in an alveolar macrophage cell line, indicating that inhalation of
brevetoxin-2 may lead to lung inflammation through an alveolar macrophage-initiated
pathway.},
issn = {1438-4639},
keywords = {Brevetoxin, Alveolar macrophages, Lung, Inflammation, Red tides},
url = {http://www.sciencedirect.com/science/article/B7GVY-50KMVYB-1/2/c663433f0a9d485dbe811fd60db49b9d}
}
@ARTICLE{Sasai2006,
author = {Sasai, Ken and Romer, Justyna T. and Lee, Youngsoo and Finkelstein,
David and Fuller, Christine and McKinnon, Peter J. and Curran, Tom},
title = {Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma
Cells: Implications for Preclinical Studies},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {4215--4222},
number = {8},
month = apr,
abstract = {Gene expression profiling indicates that the Sonic Hedgehog (Shh)
pathway is active in [~]30% of human medulloblastomas, suggesting
that it could provide a useful therapeutic target. Previously, we
showed that spontaneous medulloblastomas in Ptc1+/-p53-/- mice could
be eradicated by treatment with a small-molecule inhibitor (HhAntag)
of Smoothened (Smo). Here, we compared the responses of mouse medulloblastoma
cells propagated in flank allografts, either directly or after culture
in vitro, to HhAntag. We found that Shh pathway activity was suppressed
in medulloblastoma cells cultured in vitro and it was not restored
when these cells were transplanted into the flank of nude mice. The
growth of these transplanted tumor cells was not inhibited by treatment
of mice with doses of HhAntag that completely suppressed Smo activity.
Interestingly, tumor cells transplanted directly into the flank maintained
Smo activity and were sensitive to treatment with HhAntag. These
findings indicate that propagation of tumor cells in culture inhibits
Smo activity in a way that cannot be reversed by transplantation
in vivo, and they raise concerns about the use of cultured tumor
cells to test the efficacy of Shh pathway inhibitors as anticancer
therapies. (Cancer Res 2006; 66(8): 4215-22)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/8/4215}
}
@ARTICLE{Sasaki2010,
author = {Sasaki, H. and Muramatsu, T. and Kwon, H.-J. and Yamamoto, H. and
Hashimoto, S. and Jung, H.-S. and Shimono, M.},
title = {Down-regulated Genes in Mouse Dental Papillae and Pulp},
journal = {Journal of Dental Research},
year = {2010},
volume = {89},
pages = {679--683},
number = {7},
month = jul,
abstract = {Important factors involved in odontogenesis in mouse dental papillae
disappear between the pre- and post-natal stages of development.
Therefore, we hypothesized that certain genes involved in odontogenesis
in dental papillae were subject to pre-/post-natal down-regulation.
Our goal was to identify, by microarray analysis, which genes were
down-regulated. Dental papillae were isolated from embryonic 16-day-,
18-day- (E16, E18), and post-natal 3-day-old (P3) murine first mandibular
molar germs and analyzed by microarray. The number of down-regulated
genes was 2269 between E16 and E18, and 3130 between E18 and P3.
Drastic down-regulation (fold change > 10.0) of Adamts4, Aldha1a2,
and Lef1 was observed at both E16 and E18, and quantitative RT-PCR
revealed a post-natal reduction in their expression (Adamts4, 1/3;
Aldh1a2, 1/13; and Lef1, 1/37). These results suggest that down-regulation
of these three genes is an important factor in normal odontogenesis
in dental papillae.},
url = {http://jdr.sagepub.com/cgi/content/abstract/89/7/679}
}
@ARTICLE{Sass2011,
author = {Sass, Andrea and Marchbank, Angela and Tullis, Elizabeth and LiPuma,
John and Mahenthiralingam, Eshwar},
title = {Spontaneous and evolutionary changes in the antibiotic resistance
of Burkholderia cenocepacia observed by global gene expression analysis},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {373},
number = {1},
abstract = {BACKGROUND:Burkholderia cenocepacia is a member of the Burkholderia
cepacia complex group of bacteria that cause infections in individuals
with cystic fibrosis. B. cenocepacia isolate J2315 has been genome
sequenced and is representative of a virulent, epidemic CF strain
(ET12). Its genome encodes multiple antimicrobial resistance pathways
and it is not known which of these is important for intrinsic or
spontaneous resistance. To map these pathways, transcriptomic analysis
was performed on: (i) strain J2315 exposed to sub-inhibitory concentrations
of antibiotics and the antibiotic potentiator chlorpromazine, and
(ii) on spontaneous mutants derived from J2315 and with increased
resistance to the antibiotics amikacin, meropenem and trimethoprim-sulfamethoxazole.
Two pan-resistant ET12 outbreak isolates recovered two decades after
J2315 were also compared to identify naturally evolved gene expression
changes.RESULTS:Spontaneous resistance in B. cenocepacia involved
more gene expression changes and different subsets of genes than
those provoked by exposure to sub inhibitory concentrations of each
antibiotic. The phenotype and altered gene expression in the resistant
mutants was also stable irrespective of the presence of the priming
antibiotic. Both known and novel genes involved in efflux, antibiotic
degradation/modification, membrane function, regulation and unknown
functions were mapped. A novel role for the phenylacetic acid (PA)
degradation pathway genes was identified in relation to spontaneous
resistance to meropenem and glucose was found to repress their expression.
Subsequently, 20 mM glucose was found to produce greater that 2-fold
reductions in the MIC of multiple antibiotics against B. cenocepacia
J2315. Mutation of an RND multidrug efflux pump locus (BCAM0925-27)
and squalene-hopene cyclase gene (BCAS0167), both upregulated after
chlorpromazine exposure, confirmed their role in resistance. The
recently isolated outbreak isolates had altered the expression of
multiple genes which mirrored changes seen in the antibiotic resistant
mutants, corroborating the strategy used to model resistance. Mutation
of an ABC transporter gene (BCAS0081) upregulated in both outbreak
strains, confirmed its role in B. cenocepacia resistance.CONCLUSIONS:Global
mapping of the genetic pathways which mediate antibiotic resistance
in B. cenocepacia has revealed that they are multifactorial, identified
potential therapeutic targets and also demonstrated that putative
catabolite repression of genes by glucose can improve antibiotic
efficacy.},
doi = {10.1186/1471-2164-12-373},
issn = {1471-2164},
pubmedid = {21781329},
url = {http://www.biomedcentral.com/1471-2164/12/373}
}
@ARTICLE{Sassano2009,
author = {Sassano, Antonella and Lo Iacono, Marco and Antico, Giovanni and
Jordan, Alison and Uddin, Shahab and Calogero, Raffaele A. and Platanias,
Leonidas C.},
title = {Regulation of leukemic cell differentiation and retinoid-induced
gene expression by statins},
journal = {Mol. Cancer Ther.},
year = {2009},
volume = {8},
pages = {615--625},
number = {3},
month = mar,
abstract = {There is emerging evidence that, beyond their cholesterol-lowering
properties, statins exhibit important antileukemic effects in vitro
and in vivo, but the precise mechanisms by which they generate such
responses remain to be determined. We have previously shown that
statins promote differentiation of acute promyelocytic leukemia cells
and enhance generation of all-trans retinoic acid (ATRA)-dependent
antileukemic responses. We now provide evidence that statin-dependent
leukemic cell differentiation requires engagement and activation
of the c-Jun NH2-terminal kinase kinase pathway. In addition, in
experiments, to define the molecular targets and mediators of statin-induced
differentiation, we found a remarkable effect of statins on ATRA-dependent
gene transcription, evidenced by the selective induction of over
400 genes by the combination of atorvastatin and ATRA. Altogether,
our studies identify novel statin molecular targets linked to differentiation,
establish that statins modulate ATRA-dependent transcription, and
suggest that combined use of statins with retinoids may provide a
novel approach to enhance antileukemic responses in acute promyelocytic
leukemia and possibly other leukemias. [Mol Cancer Ther 2009;8(3):615-25]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/8/3/615}
}
@ARTICLE{Sathiamoorthy2011,
author = {Sathiamoorthy, Sarmitha and Hodgins, Douglas C. and Shewen, Patricia
E. and Highlander, Sarah K. and Lo, Reggie Y.C.},
title = {A snap-shot of Mannheimia hemolyticaA1 gene expression during infection
in the bovine host},
journal = {FEMS Microbiology Letters},
year = {2011},
volume = {325},
pages = {148--154},
number = {2},
abstract = {It is expected that Mannheimia hemolyticaA1 expresses a particular
collection of genes during infection in the host. The bacterial gene
products are produced in the in vivo environment to facilitate growth
and survival. Here, we examined gene expression by M. hemolyticaA1
in the bovine host after 6 days of infection. Total RNA from M. hemolyticaA1
recovered from pneumonic lungs of two animals was used to produce
cDNA to screen a custom M. hemolyticaA1 microarray. The expression
profile was compared to a RNA sample from an in vitro grown culture.
The data showed that 44 genes were differentially expressed by more
than eightfold when compared with the in vitro sample. Seventeen
genes were found to have higher expression in vivo and 27 genes had
lower expression. Several virulence-associated genes including those
encoding leukotoxin, a capsule biosynthetic enzyme and the serotype-specific
antigen, Ssa, had reduced expression, suggesting that their products
may not be important during the later stages of infection. Most of
the genes up-regulated in vivo encoded hypothetical or conserved
hypothetical proteins. Three Mu-like bacteriophage-related genes
were up-regulated in the in vivo sample, suggesting that the prophage
may be transcriptionally active. The results provide a glimpse of
gene expression by the bacterium in the host after pulmonary infection
has been established.},
doi = {10.1111/j.1574-6968.2011.02422.x},
issn = {1574-6968},
keywords = {Pasteurella, Mannheimia, bovine pneumonic pasteurellosis, gene expression,
in vivo, respiratory disease},
url = {http://dx.doi.org/10.1111/j.1574-6968.2011.02422.x}
}
@ARTICLE{Sathira2010,
author = {Sathira, Nuankanya and Yamashita, Riu and Tanimoto, Kousuke and Kanai,
Akinori and Arauchi, Takako and Kanematsu, Soutaro and Nakai, Kenta
and Suzuki, Yutaka and Sugano, Sumio},
title = {Characterization of Transcription Start Sites of Putative Non-coding
RNAs by Multifaceted Use of Massively Paralleled Sequencer},
journal = {DNA Res},
year = {2010},
volume = {17},
pages = {169--183},
number = {3},
month = jun,
abstract = {On the basis of integrated transcriptome analysis, we show that not
all transcriptional start site clusters (TSCs) in the intergenic
regions (iTSCs) have the same properties; thus, it is possible to
discriminate the iTSCs that are likely to have biological relevance
from the other noise-level iTSCs. We used a total of 251 933 381
short-read sequence tags generated from various types of transcriptome
analyses in order to characterize 6039 iTSCs, which have significant
expression levels. We analyzed and found that 23% of these iTSCs
were located in the proximal regions of the RefSeq genes. These RefSeq-linked
iTSCs showed similar expression patterns with the neighboring RefSeq
genes, had widely fluctuating transcription start sites and lacked
ordered nucleosome positioning. These iTSCs seemed not to form independent
transcriptional units, simply representing the by-products of the
neighboring RefSeq genes, in spite of their significant expression
levels. Similar features were also observed for the TSCs located
in the antisense regions of the RefSeq genes. Furthermore, for the
remaining iTSCs that were not associated with any RefSeq genes, we
demonstrate that integrative interpretation of the transcriptome
data provides essential information to specify their biological functions
in the hypoxic responses of the cells.},
url = {http://dnaresearch.oxfordjournals.org/cgi/content/abstract/17/3/169}
}
@ARTICLE{Sathirapongsasuti2011,
author = {Sathirapongsasuti, J. Fah and Sathira, Nuankanya and Suzuki, Yutaka
and Huttenhower, Curtis and Sugano, Sumio},
title = {Ultraconserved cDNA segments in the human transcriptome exhibit resistance
to folding and implicate function in translation and alternative
splicing},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {1967--1979},
number = {6},
month = mar,
abstract = {Ultraconservation, defined as perfect human-to-rodent sequence identity
at least 200-bp long, is a strong indicator of evolutionary and functional
importance and has been explored extensively at the genome level.
However, it has not been investigated at the transcript level, where
such extreme conservation might highlight loci with important post-transcriptional
regulatory roles. We present 96 ultraconserved cDNA segments (UCSs),
stretches of human mature mRNAs that match identically with orthologous
regions in the mouse and rat genomes. UCSs can span multiple exons,
a feature we leverage here to elucidate the role of ultraconservation
in post-transcriptional regulation. UCS sites are implicated in functions
at essentially every post-transcriptional stage: pre-mRNA splicing
and degradation through alternative splicing and nonsense-mediated
decay (AS-NMD), mature mRNA silencing by miRNA, fast mRNA decay rate
and translational repression by upstream AUGs. We also found UCSs
to exhibit resistance to formation of RNA secondary structure. These
multiple layers of regulation underscore the importance of the UCS-containing
genes as key global RNA processing regulators, including members
of the serine/arginine-rich protein and heterogeneous nuclear ribonucleoprotein
(hnRNP) families of essential splicing regulators. The discovery
of UCSs shed new light on the multifaceted, fine-tuned and tight
post-transcriptional regulation of gene families as conserved through
the majority of the mammalian lineage.},
comment = {10.1093/nar/gkq949},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/6/1967}
}
@ARTICLE{Sathish2009,
author = {Sathish, Venkatachalem and Thompson, Michael A. and Bailey, Jeffrey
P. and Pabelick, Christina M. and Prakash, Y. S. and Sieck, Gary
C.},
title = {Effect of proinflammatory cytokines on regulation of sarcoplasmic
reticulum Ca2+ reuptake in human airway smooth muscle},
journal = {Am J Physiol Lung Cell Mol Physiol},
year = {2009},
volume = {297},
pages = {L26--34},
number = {1},
month = jul,
abstract = {Airway inflammation leads to increased intracellular Ca2+ ([Ca2+]i)
levels in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum
Ca2+ release and reuptake are key components of ASM [Ca2+]i regulation.
Ca2+ reuptake occurs via sarcoendoplasmic reticulum Ca2+ ATPase (SERCA)
and is regulated by the inhibitory protein phospholamban (PLB) in
many cell types. In human ASM, we tested the hypothesis that inflammation
increases PLB, thus inhibiting SERCA function, and leading to maintained
[Ca2+]i levels. Surprisingly, we found that human ASM does not express
PLB protein (although mRNA is detectable). Overnight exposure to
the proinflammatory cytokines TNF{alpha} and IL-13 did not induce
PLB expression, raising the issue of how SERCA is regulated. We then
found that direct SERCA phosphorylation (via CaMKII) occurs in human
ASM. In fura-2-loaded human ASM cells, we found that the CaMKII antagonist
KN-93 significantly slowed the rate of fall of [Ca2+]i transients
induced by ACh or bradykinin (in zero extracellular Ca2+), suggesting
a role for CaMKII-mediated SERCA regulation. SERCA expression was
decreased by cytokine exposure, and the rate of fall of [Ca2+]i transients
was slowed in cells exposed to TNF{alpha} and IL-13. Cytokine effects
on Ca2+ reuptake were unaffected by additional exposure to KN-93.
These data indicate that in human ASM, SERCA is regulated by mechanisms
such as CaMKII and that airway inflammation maintains [Ca2+]i levels
by decreasing SERCA expression and slowing Ca2+ reuptake.},
url = {http://ajplung.physiology.org/cgi/content/abstract/297/1/L26}
}
@ARTICLE{Sathyanarayana2007,
author = {Sathyanarayana, Ubaradka and Riley, Janice and Nagle, Raymond and
Miller, Phillip and Pestano, Gary},
title = {Molecular classification of prostate cancer recurrence using multiplexed
mRNA detection from FFPE samples.},
journal = {AACR Meeting Abstracts},
year = {2007},
volume = {2007},
pages = {B8--},
number = {2_Molecular_Diagnostics_Meeting},
month = sep,
url = {http://www.aacrmeetingabstracts.org}
}
@ARTICLE{Satish2011,
author = {Satish, Latha and Gallo, Phillip and Baratz, Mark and Johnson, Sandra
and Kathju, Sandeep},
title = {Reversal of TGF-beta1 stimulation of alpha-smooth muscle actin and
extracellular matrix components by cyclic AMP in Dupuytren's - derived
fibroblasts},
journal = {BMC Musculoskeletal Disorders},
year = {2011},
volume = {12},
pages = {113},
number = {1},
abstract = {BACKGROUND:Myofibroblasts, a derived subset of fibroblasts especially
important in scar formation and wound contraction, have been found
at elevated levels in affected Dupuytren's tissues. Transformation
of fibroblasts to myofibroblasts is characterized by expression of
alpha- smooth muscle actin (alpha-SMA) and increased production of
extracellular matrix (ECM) components, both events of relevance to
connective tissue remodeling. We propose that increasing the activation
of the cyclic AMP (cAMP)/protein kinase A signaling pathway will
inhibit transforming growth factor-beta1 (TGF-beta1)-induced ECM
synthesis and myofibroblast formation and may provide a means to
blunt fibrosis.METHODS:Fibroblasts derived from areas of Dupuytren's
contracture cord (DC), from adjacent and phenotypically normal palmar
fascia (PF), and from palmar fascia from patients undergoing carpal
tunnel release (CTR; CT) were treated with TGF-beta1 (2 ng/ml) and/or
forskolin (10 muM) (a known stimulator of cAMP). Total RNA and protein
extracted was subjected to real time RT-PCR and Western blot analysis.RESULTS:The
basal mRNA expression levels of fibronectin- extra domain A (FN1-EDA),
type I (COL1A2) and type III collagen (COL3A1), and connective tissue
growth factor (CTGF) were all significantly increased in DC- and
in PF-derived cells compared to CT-derived fibroblasts. The TGF-beta1
stimulation of alpha-SMA, CTGF, COL1A2 and COL3A1 was greatly inhibited
by concomitant treatment with forskolin, especially in DC-derived
cells. In contrast, TGF-beta1 stimulation of FN1-EDA showed similar
levels of reduction with the addition of forskolin in all three cell
types.CONCLUSION:In sum, increasing cAMP levels show potential to
inhibit the formation of myofibroblasts and accumulation of ECM components.
Molecular agents that increase cAMP may therefore prove useful in
mitigating DC progression or recurrence.},
doi = {10.1186/1471-2474-12-113},
issn = {1471-2474},
pubmedid = {21612641},
url = {http://www.biomedcentral.com/1471-2474/12/113}
}
@ARTICLE{Satish2008,
author = {Satish, Latha and LaFramboise, William and O'Gorman, David and Johnson,
Sandra and Janto, Benjamin and Gan, Bing and Baratz, Mark and Hu,
Fen and Post, J Christopher and Ehrlich, Garth and Kathju, Sandeep},
title = {Identification of differentially expressed genes in fibroblasts derived
from patients with Dupuytren's Contracture},
journal = {BMC Medical Genomics},
year = {2008},
volume = {1},
pages = {10},
number = {1},
abstract = {Dupuytren's contracture (DC) is the most common inherited connective
tissue disease of humans and is hypothesized to be associated with
aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts
are believed to play an important role in the genesis of DC and the
fibroproliferation and contraction that are hallmarks of this disease.
This study compares the gene expression profiles of fibroblasts isolated
from DC patients and controls in an attempt to identify key genes
whose regulation might be significantly altered in fibroblasts found
within the palmar fascia of Dupuytren's patients. Total RNA isolated
from diseased palmar fascia (DC) and normal palmar fascia (obtained
during carpal tunnel release; 6 samples per group) was subjected
to quantitative analyses using two different microarray platforms
(GE Code Link™ and Illumina™) to identify and validate differentially
expressed genes. The data obtained was analyzed using The Significance
Analysis of Microarrays (SAM) software through which we identified
69 and 40 differentially regulated gene transcripts using the CodeLink™
and Illumina™ platforms, respectively. The CodeLink™ platform identified
18 upregulated and 51 downregulated genes. Using the Illumina™ platform,
40 genes were identified as downregulated, eleven of which were identified
by both platforms. Quantitative RT-PCR confirmed the downregulation
of three high-interest candidate genes which are all components of
the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1)
transcript variant D, and type XV collagen alpha 1 chain. Overall,
our study has identified a variety of candidate genes that may be
involved in the pathophysiology of Dupuytren's contracture and may
ultimately serve as attractive molecular targets for alternative
therapies.},
doi = {10.1186/1755-8794-1-10},
issn = {1755-8794},
pubmedid = {18433489},
url = {http://www.biomedcentral.com/1755-8794/1/10}
}
@ARTICLE{Satish2006,
author = {Satish, Latha and Lyons-Weiler, James and Hebda, Patricia A. and
Wells, Alan},
title = {Gene expression patterns in isolated keloid fibroblasts},
journal = {Wound Repair and Regeneration},
year = {2006},
volume = {14},
pages = {463--470},
number = {4},
abstract = {ABSTRACT Keloid scars after skin trauma are a significant clinical
problem, especially in black populations, in which the incidence
of keloids has been estimated at 4–16%. Keloids are abnormal dermal
proliferative scars secondary to dysregulated wound healing. Despite
several biochemical studies on the role of extracellular matrix proteins
and growth factors during keloid formation, we still do not know
what molecules and signals induce this change. Fibroblasts are thought
to be the major inductive cell for keloid scar formation. The aim
of this study was to identify gene expression patterns that characterize
keloid fibroblasts; identifying such genetic disequilibrium may shed
light on the molecular signaling events responsible for keloid formation.
In this study, we performed gene expression analysis of fibroblasts
isolated from keloid lesions from three individuals in comparison
with the fibroblasts isolated from normal skin using the Affymetrix
U133a chip (22,284 genes and expression sequence tags). We found
through J5 test score expression analysis that among 22,284 genes,
there were 43 genes that were overexpressed and five genes were underexpressed
in keloid fibroblasts when compared with dermal fibroblasts from
persons without keloids. The overexpression of three genes not previously
reported as being up-regulated in keloids (annexin A2, Transgelin,
and RPS18) was confirmed by real-time polymerase chain reaction.
Certain overexpressed genes were similar to previous biochemical
observations on the protein levels of these overexpressed genes during
keloid formation. We also report for the first time that a few tumor-related
genes are overexpressed in keloid fibroblasts.},
issn = {1524-475X},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1743-6109.2006.00135.x}
}
@ARTICLE{Sato2008,
author = {Sato, Akira and Hiramoto, Akiko and Uchikubo, Yusuke and Miyazaki,
Eriko and Satake, Akito and Naito, Tomoharu and Hiraoka, Osamu and
Miyake, Tsuyoshi and Kim, Hye-Sook and Wataya, Yusuke},
title = {Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2'-deoxyuridine},
journal = {Genomics},
year = {2008},
volume = {92},
pages = {9--17},
number = {1},
month = jul,
abstract = {5-Fluoro-2'-deoxyuridine (FUdR), a potent anticancer agent, exerts
its effects by inhibiting thymidylate synthase, an essential machinery
for DNA synthesis in cell proliferation. Also, cell death is caused
by FUdR, primarily due to an imbalance in the nucleotide pool resulting
from this enzyme inhibition. We have investigated the cancer cell
death induced by FUdR, focusing on its molecular mechanisms. Using
mouse mammary tumor FM3A cell lines, the original clone F28-7 and
its variant F28-7-A cells, we previously reported an interesting
observation that FUdR induces a necrotic morphology in F28-7, but
induces, in contrast, an apoptotic morphology in F28-7-A cells. In
the present study, to understand the molecular mechanisms underlying
these differential cell deaths, i.e., necrosis and apoptosis, we
investigated the gene expression changes occurring in these processes.
Using the cDNA microarray technology, we found 215 genes being expressed
differentially in the necrosis and apoptosis. Further analysis revealed
differences between these cell lines in terms of the expressions
of both a cluster of heat shock protein (HSP)-related genes and a
cluster of apoptosis-related genes. Notably, inhibition of HSP90
in F28-7 cells caused a shift from the FUdR-induced necrosis into
apoptosis. These findings are expected to lead to a better understanding
of this anticancer drug FUdR for its molecular mechanisms and also
of the general biological issue, necrosis and apoptosis.},
issn = {0888-7543},
keywords = {5-Fluoro-2'-deoxyuridine, Microarray analysis, Gene expression profile,
Cell death, Necrosis, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6WG1-4ST3VN5-2/2/74db405f21119aadb89acaa54252580f}
}
@ARTICLE{Sato2007,
author = {Sato, Akira and Nishimura, Yukio and Oishi, Takao and Higo, Noriyuki
and Murata, Yumi and Onoe, Hirotaka and Saito, Kimika and Tsuboi,
Fumiharu and Takahashi, Masahito and Isa, Tadashi and Kojima, Toshio},
title = {Differentially expressed genes among motor and prefrontal areas of
macaque neocortex},
journal = {Biochemical and Biophysical Research Communications},
year = {2007},
volume = {362},
pages = {665--669},
number = {3},
month = oct,
abstract = {In higher primates, the motor-related areas of the neocortex are highly
differentiated into several subareas based on both functional and
cytoarchitectural aspects. To assess the molecular basis of this
areal specialization, we investigated the gene expression profiles
of the primary motor area (M1), premotor area (dorsal and ventral,
PMd and PMv, respectively), and prefrontal area (A46) in rhesus monkeys
using DNA microarray. We discovered that 476 genes were differentially
expressed among these 4 areas. More than half of these genes were
most abundantly expressed in M1, and most genes were complementarily
expressed between M1 and A46. The expression profiles of PMd and
PMv were quite similar to each other and different from those of
M1 and A46. The data will provide a fundamental basis for the further
analysis of the structure-function relationship of the primate brain.},
issn = {0006-291X},
keywords = {Gene expression, DNA microarray, Cerebral neocortex, Rhesus monkey,
Primary motor area, Premotor area, Prefrontal area},
url = {http://www.sciencedirect.com/science/article/B6WBK-4PG2JJ9-6/2/76e8dc033aadefafcc6e957f631b771d}
}
@ARTICLE{Sato2011,
author = {Sato, Keiichiro and Awasaki, Yasuyuki and Kandori, Hitoshi and Tanakamaru,
Zen-yo and Nagai, Hirofumi and Baron, David and Yamamoto, Masaki},
title = {Suppressive effects of acid-forming diet against the tumorigenic
potential of pioglitazone hydrochloride in the urinary bladder of
male rats},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {251},
pages = {234--244},
number = {3},
month = mar,
abstract = {Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated
receptor gamma (PPAR[gamma]) agonist, was administered orally for
85 weeks at 16 mg/kg/day to male rats fed either a diet containing
1.5% ammonium chloride (acid-forming diet) or a control diet to investigate
the effects of urinary acidification induced by the acid-forming
diet on the tumorigenic potential of PIO in the urinary bladder.
The surviving animals at the end of the administration period were
followed to the end of the 2-year study period without changes in
the diet and were subjected to terminal necropsy on Week 104. The
number of urinary microcrystals, evaluated by manual counting with
light microscopy and by an objective method with a laser diffraction
particle size analyzer, was increased by PIO on Weeks 12 and 25 and
the increases were markedly suppressed by urinary acidification.
Urinary citrate was decreased by PIO throughout the study period,
but no changes were seen in urinary oxalate at any timepoint. The
incidences of PIO-treated males bearing at least one of the advanced
proliferative changes consisting of papillary hyperplasia, nodular
hyperplasia, papilloma or carcinoma were significantly decreased
from 11 of 82 males fed the control diet to 2 of 80 males fed the
acid-forming diet. The acid-forming diet did not show any effects
on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria
appears to be involved in the development of the advanced stage proliferative
lesions in bladder tumorigenesis induced by PIO in male rats.},
issn = {0041-008X},
keywords = {Pioglitazone, Urinary bladder, Tumor, Hyperplasia, PPAR, Rats},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11000159}
}
@ARTICLE{Sato2011a,
author = {Sato, Shusei and Hirakawa, Hideki and Isobe, Sachiko and Fukai, Eigo
and Watanabe, Akiko and Kato, Midori and Kawashima, Kumiko and Minami,
Chiharu and Muraki, Akiko and Nakazaki, Naomi and Takahashi, Chika
and Nakayama, Shinobu and Kishida, Yoshie and Kohara, Mitsuyo and
Yamada, Manabu and Tsuruoka, Hisano and Sasamoto, Shigemi and Tabata,
Satoshi and Aizu, Tomoyuki and Toyoda, Atsushi and Shin-i, Tadasu
and Minakuchi, Yohei and Kohara, Yuji and Fujiyama, Asao and Tsuchimoto,
Suguru and Kajiyama, Shin'ichiro and Makigano, Eri and Ohmido, Nobuko
and Shibagaki, Nakako and Cartagena, Joyce A. and Wada, Naoki and
Kohinata, Tsutomu and Atefeh, Alipour and Yuasa, Shota and Matsunaga,
Sachihiro and Fukui, Kiichi},
title = {Sequence Analysis of the Genome of an Oil-Bearing Tree, Jatropha
curcas L.},
journal = {DNA Res},
year = {2011},
volume = {18},
pages = {65--76},
number = {1},
month = feb,
abstract = {The whole genome of Jatropha curcas was sequenced, using a combination
of the conventional Sanger method and new-generation multiplex sequencing
methods. Total length of the non-redundant sequences thus obtained
was 285 858 490 bp consisting of 120 586 contigs and 29 831 singlets.
They accounted for [~]95% of the gene-containing regions with the
average G + C content was 34.3%. A total of 40 929 complete and partial
structures of protein encoding genes have been deduced. Comparison
with genes of other plant species indicated that 1529 (4%) of the
putative protein-encoding genes are specific to the Euphorbiaceae
family. A high degree of microsynteny was observed with the genome
of castor bean and, to a lesser extent, with those of soybean and
Arabidopsis thaliana. In parallel with genome sequencing, cDNAs derived
from leaf and callus tissues were subjected to pyrosequencing, and
a total of 21 225 unigene data have been generated. Polymorphism
analysis using microsatellite markers developed from the genomic
sequence data obtained was performed with 12 J. curcas lines collected
from various parts of the world to estimate their genetic diversity.
The genomic sequence and accompanying information presented here
are expected to serve as valuable resources for the acceleration
of fundamental and applied research with J. curcas, especially in
the fields of environment-related research such as biofuel production.
Further information on the genomic sequences and DNA markers is available
at http://www.kazusa.or.jp/jatropha/.},
comment = {10.1093/dnares/dsq030},
url = {http://dnaresearch.oxfordjournals.org/cgi/content/abstract/18/1/65}
}
@ARTICLE{Sato2011d,
author = {Sato, Takatoshi and Iso, Yoshitaka and Uyama, Taro and Kawachi, Keisuke
and Wakabayashi, Kohei and Omori, Yasutoshi and Soda, Teruko and
Shoji, Makoto and Koba, Shinji and Yokoyama, Shin-Ichiro and Fukuda,
Noboru and Saito, Satoshi and Katagiri, Takashi and Kobayashi, Youichi
and Takeyama, Youichi and Umezawa, Akihiro and Suzuki, Hiroshi},
title = {Coronary vein infusion of multipotent stromal cells from bone marrow
preserves cardiac function in swine ischemic cardiomyopathy via enhanced
neovascularization},
journal = {Lab Invest},
year = {2011},
volume = {91},
pages = {553--564},
number = {4},
month = apr,
issn = {0023-6837},
publisher = {United States and Canadian Academy of Pathology, Inc.},
url = {http://dx.doi.org/10.1038/labinvest.2010.202}
}
@ARTICLE{Sato2003,
author = {Sato, Toshiyuki and Odagiri, Hiroki and Ikenaga, Shojiro-Kazunori
and Maruyama, Masateru and Sasaki, Mutsuo},
title = {Chemosensitivity of human pancreatic carcinoma cells is enhanced
by IkBα super-repressor},
journal = {Cancer Science},
year = {2003},
volume = {94},
pages = {467--472},
number = {5},
abstract = {Pancreatic cancer has an unfavorable prognosis; surgery and chemotherapy
at present have only limited value. To improve the prognosis of pancreatic
cancer, effective non-surgical therapy is necessary. NF-kB is reported
to be related to resistance to apopto-sis, but its role in Chemosensitivity
remains controversial. We examined the effects on Chemosensitivity
of inhibition by induction of the super-repressor IkBα in pancreatic
cancer cell lines, BxPC-3, Capan-1 and Panc-1. IkBα protein was
transduced by infection of adenovirus vector AxCAhlkBδN. Sensitivity
to VP-16 and doxorubicin was increased significantly by IkBα induction
in all three pancreatic cell lines. To investigate molecular events
during IkBα induction, we examined the changes in expression of
drug-resistance-related genes by real-time RT-PCR and those in apoptosis-related
genes by cDNA microarray. There was no common change of gene expression
before and after IkBα induction among the three pancreatic cancer
cell lines, except for mdm2. Further examination of other genes is
necessary for a better understanding of the molecular mechanisms
of enhancement of Chemosensitivity through IkBα induction. However,
we have confirmed that IkBα induction leads to an increase of Chemosensitivity
of pancreatic cancer. Many problems remain before clinical application
of this adenoviral system will be feasible, but our results may ultimately
lead to an improved therapy of pancreatic cancer. (Cancer Sci 2003;
94: 467–472)},
issn = {1349-7006},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1349-7006.2003.tb01466.x}
}
@ARTICLE{Sato2008a,
author = {Sato, Takatoshi and Suzuki, Hiroshi and Kusuyama, Taro and Omori,
Yasutoshi and Soda, Teruko and Tsunoda, Fumiyoshi and Shoji, Makoto
and Iso, Yoshitaka and Koba, Shinji and Geshi, Eiichi and Katagiri,
Takashi and Kawachi, Keisuke and Wakabayashi, Kohei and Takeyama,
Youichi},
title = {G-CSF after myocardial infarction accelerates angiogenesis and reduces
fibrosis in swine},
journal = {International Journal of Cardiology},
year = {2008},
volume = {127},
pages = {166--173},
number = {2},
month = jul,
abstract = {Objective Recent studies have suggested that granulocyte colony-stimulating
factor (G-CSF) may improve cardiac function after acute myocardial
infarction (AMI) by accelerating angiogenesis or cardiomyogenesis,
but negative results and side effect of G-CSF have also been reported.
However, no previous studies have used large animal models of ischemia/reperfusion
to investigate the effect and side effect of G-CSF after AMI.Methods
The diagonal branch of the left anterior descending coronary artery
of swine was balloon-occluded for 1 h and then reperfused. The animals
of the G-CSF group were injected with G-CSF subcutaneously (5.0 [mu]g/kg/day)
for 6 days after MI and then sacrificed after 4 weeks. The control
group received the same volume of saline.Results There were no differences
between the groups in the rate of thrombotic obstruction or progression
of stenosis lesion in coronary angiography. The ejection fraction
and end-diastolic volume in the G-CSF group were not significantly
improved over the control values. The fibrotic area was significantly
smaller in the G-CSF group than in the controls (P < 0.05), and the
numbers of vessels counted in anti-von Willebrand factor and anti-[alpha]-smooth
muscle actin-stained sections were significantly larger (P < 0.005
and P < 0.05, respectively). The expression of collagen III mRNA
was significantly lower in the G-CSF group than in the control in
the infarct (P < 0.0005) and border areas (P < 0.005), and TGF-[beta]
mRNA was significantly lower in the G-CSF group in the border area
(P < 0.05).Conclusions G-CSF could modify the healing process after
AMI by accelerating angiogenesis in a swine ischemia/reperfusion
model. At the dose administered, however, G-CSF did not seem to improve
the global cardiac function.},
issn = {0167-5273},
keywords = {G-CSF, Myocardial infarction, Angiogenesis, Remodeling},
url = {http://www.sciencedirect.com/science/article/B6T16-4PCR1HG-1/2/3858a612379be7d3421daf5940e6de4f}
}
@ARTICLE{Sato2011c,
author = {Sato, Yutaka and Antonio, Baltazar and Namiki, Nobukazu and Motoyama,
Ritsuko and Sugimoto, Kazuhiko and Takehisa, Hinako and Minami, Hiroshi
and Kamatsuki, Kaori and Kusaba, Makoto and Hirochika, Hirohiko and
Nagamura, Yoshiaki},
title = {Field transcriptome revealed critical developmental and physiological
transitions involved in the expression of growth potential in japonica
rice},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {10},
number = {1},
abstract = {BACKGROUND:Plant growth depends on synergistic interactions between
internal and external signals, and yield potential of crops is a
manifestation of how these complex factors interact, particularly
at critical stages of development. As an initial step towards developing
a systems-level understanding of the biological processes underlying
the expression of overall agronomic potential in cereal crops, a
high-resolution transcriptome analysis of rice was conducted throughout
life cycle of rice grown under natural field conditions.RESULTS:A
wide range of gene expression profiles based on 48 organs and tissues
at various developmental stages identified 731 organ/tissue specific
genes as well as 215 growth stage-specific expressed genes universally
in leaf blade, leaf sheath, and root. Continuous transcriptome profiling
of leaf from transplanting until harvesting further elucidated the
growth-stage specificity of gene expression and uncovered two major
drastic changes in the leaf transcriptional program. The first major
change occurred before the panicle differentiation, accompanied by
the expression of RFT1, a putative florigen gene in long day conditions,
and the downregulation of the precursors of two microRNAs. This transcriptome
change was also associated with physiological alterations including
phosphate-homeostasis state as evident from the behavior of several
key regulators such as miR399. The second major transcriptome change
occurred just after flowering, and based on analysis of sterile mutant
lines, we further revealed that the formation of strong sink, i.e.,
a developing grain, is not the major cause but is rather a promoter
of this change.CONCLUSIONS:Our study provides not only the genetic
basis for functional genomics in rice but also new insight into understanding
the critical physiological processes involved in flowering and seed
development, that could lead to novel strategies for optimizing crop
productivity.},
doi = {10.1186/1471-2229-11-10},
issn = {1471-2229},
pubmedid = {21226959},
url = {http://www.biomedcentral.com/1471-2229/11/10}
}
@ARTICLE{Sato2011b,
author = {Sato, Youichi and Koshioka, Sakura and Kirino, Yasushi and Kamimoto,
Takayuki and Kawazoe, Kazuyoshi and Abe, Shinji and Minakuchi, Kazuo
and Nakahori, Yutaka},
title = {Role of dipeptidyl peptidase IV (DPP4) in the development of dyslipidemia:
DPP4 contributes to the steroid metabolism pathway},
journal = {Life Sciences},
year = {2011},
volume = {88},
pages = {43--49},
number = {1-2},
month = jan,
abstract = {Aims We previously reported that dipeptidyl peptidase IV (DPP4)-deficient
rats were susceptible to dyslipidemia induced by streptozotocin (STZ).
Hence, it is suggested that DPP4 is important for lipid metabolism.Main
methods In this study, to verify the role of DPP4 in the development
of dyslipidemia, we carried out a microarray analysis of the livers
of STZ-treated wild-type and DPP4-deficient rats and showed that
the expression levels of genes involved in metabolic processes (steroid
metabolic processes and cellular lipid metabolic processes) were
significantly altered by STZ treatment.Key findings In the wild-type
rats, the expression of hydroxysteroid (17-beta) dehydrogenase 2
(Hsd7b2), which catalyzes sex steroid synthesis from cholesterol,
was significantly increased by about 15-fold after STZ treatment;
however, it did not change in the DPP4-deficient rats. In the STZ
untreated group of DPP4-deficient rats, the expression levels of
cytochrome P450, subfamily 51 (Cyp51) and sterol-C4-methyl oxidase-like
(Sc4mol), which catalyze intermediate steps in cholesterol synthesis,
were significantly elevated compared to those of other groups. Similar
results were demonstrated in HuH7-cells after DPP4 overexpression
or the addition of human sera containing DPP4.Significance DPP4 is
crucial for regulating the expression of factors related to steroid
metabolism such as Cyp51, Sc4mol, and Hsd17b2, and DPP4 deficiency
or inhibition may cause dyslipidemia.},
issn = {0024-3205},
keywords = {DPP4 deficient, Streptozotocin, Diabetes, Steroid metabolism, Dyslipidemia},
url = {http://www.sciencedirect.com/science/article/pii/S0024320510004807}
}
@ARTICLE{Satoh2010,
author = {Satoh, Kouji and Kondoh, Hiroaki and Sasaya, Takahide and Shimizu,
Takumi and Choi, Il-Ryong and Omura, Toshihiro and Kikuchi, Shoshi},
title = {Selective modification of rice (Oryza sativa) gene expression by
rice stripe virus infection},
journal = {J. Gen. Virol.},
year = {2010},
volume = {91},
pages = {294--305},
number = {1},
month = jan,
abstract = {Rice stripe disease, caused by rice stripe virus (RSV), is one of
the major virus diseases in east Asia. Rice plants infected with
RSV usually show symptoms such as chlorosis, weakness, necrosis in
newly emerged leaves and stunting. To reveal rice cellular systems
influenced by RSV infection, temporal changes in the transcriptome
of RSV-infected plants were monitored by a customized rice oligoarray
system. The transcriptome changes in RSV-infected plants indicated
that protein-synthesis machineries and energy production in the mitochondrion
were activated by RSV infection, whereas energy production in the
chloroplast and synthesis of cell-structure components were suppressed.
The transcription of genes related to host-defence systems under
hormone signals and those for gene silencing were not activated at
the early infection phase. Together with concurrent observation of
virus concentration and symptom development, such transcriptome changes
in RSV-infected plants suggest that different sets of various host
genes are regulated depending on the development of disease symptoms
and the accumulation of RSV.},
url = {http://vir.sgmjournals.org/cgi/content/abstract/91/1/294}
}
@ARTICLE{Satoh2011,
author = {Satoh, Masaaki and Saito, Makoto and Takano, Takashi and Kasama,
Yuri and Nishimura, Tomohiro and Nishito, Yasumasa and Hirata, Yuichi
and Arai, Masaaki and Sudoh, Masayuki and Kai, Chieko and Kohara,
Michinori and Tsukiyama-Kohara, Kyoko},
title = {Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection
Through Betaine/GABA Transporter-1},
journal = {The Journal of Infectious Disease},
year = {2011},
volume = {204},
pages = {1172-1180},
number = {8},
abstract = {Background. We recently established a monoclonal antibody (2-152a
MAb) that binds to 3{beta}-hydroxysterol-{Delta}24-reductase (DHCR24)
by immunizing mice with cells (RzM6-LC) persistently expressing hepatitis
C virus (HCV). Here, we aimed to analyze the activity of 2-152a MAb
against HCV replication and explore the molecular mechanism underlying
the antiviral activity. Methods. We characterized the effects of
2-152a MAb on HCV replication and performed a microarray analysis
of antibody-treated HCV replicon cells. The molecules showing a significant
change after the antibody treatment were screened to examine their
relationship with HCV replication. Results. The antibody had antiviral
activity both in vitro and in vivo (chimeric mice). In the microarray
analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA
transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured
cells. Silencing of BGT-1 expression by small interfering RNA (siRNA)
revealed significant suppression of HCV replication and infection
without cytotoxicity. Further, BGT-1 expression was significantly
increased in the presence of HCV (P < .05). Conclusions. Our results
suggest that 2-152a MAb suppresses HCV replication and infection
through BGT-1. These findings highlight important roles of BGT-1
in HCV replication and reveal a possible target for anti-HCV therapy.},
doi = {10.1093/infdis/jir501},
eprint = {http://jid.oxfordjournals.org//cgi/reprint/204/8/1172.pdf},
url = {http://jid.oxfordjournals.org//cgi/content/abstract/204/8/1172}
}
@ARTICLE{Satterfield2007,
author = {Satterfield, Brent C. and Stern, Seth and Caplan, Michael R. and
Hukari, Kyle W. and West, Jay A. A.},
title = {Microfluidic Purification and Preconcentration of mRNA by Flow-Through
Polymeric Monolith},
journal = {Analytical Chemistry},
year = {2007},
volume = {79},
pages = {6230-6235},
number = {16},
doi = {10.1021/ac0709201},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac0709201},
url = {http://pubs.acs.org/doi/abs/10.1021/ac0709201}
}
@ARTICLE{Satterfield2009,
author = {Satterfield, M. Carey and Song, Gwonhwa and Kochan, Kelli J. and
Riggs, Penny K. and Simmons, Rebecca M. and Elsik, Christine G. and
Adelson, David L. and Bazer, Fuller W. and Zhou, Huaijun and Spencer,
Thomas E.},
title = {Discovery of candidate genes and pathways in the endometrium regulating
ovine blastocyst growth and conceptus elongation},
journal = {Physiol Genomics},
year = {2009},
volume = {39},
pages = {85--99},
number = {2},
month = oct,
abstract = {Establishment of pregnancy in ruminants requires blastocyst growth
to form an elongated conceptus that produces interferon tau, the
pregnancy recognition signal, and initiates implantation. Blastocyst
growth and development requires secretions from the uterine endometrium.
An early increase in circulating concentrations of progesterone (P4)
stimulates blastocyst growth and elongation in ruminants. This study
utilized sheep as a model to identify candidate genes and regulatory
networks in the endometrium that govern preimplantation blastocyst
growth and development. Ewes were treated daily with either P4 or
corn oil vehicle from day 1.5 after mating to either day 9 or day
12 of pregnancy when endometrium was obtained by hysterectomy. Microarray
analyses revealed many differentially expressed genes in the endometria
affected by day of pregnancy and early P4 treatment. In situ hybridization
analyses revealed that many differentially expressed genes were expressed
in a cell-specific manner within the endometrium. The Database for
Annotation, Visualization, and Integrated Discovery (DAVID) was used
to identify functional groups of genes and biological processes in
the endometrium that are associated with growth and development of
preimplantation blastocysts. Notably, biological processes affected
by day of pregnancy and/or early P4 treatment included lipid biosynthesis
and metabolism, angiogenesis, transport, extracellular space, defense
and inflammatory response, proteolysis, amino acid transport and
metabolism, and hormone metabolism. This transcriptomic data provides
novel insights into the biology of endometrial function and preimplantation
blastocyst growth and development in sheep.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/39/2/85}
}
@ARTICLE{Saturno2007,
author = {Saturno, Grazia and Pesenti, Manuela and Cavazzoli, Cristiano and
Rossi, Anna and Giusti, Anna M. and Gierke, Berthold and Pawlak,
Michael and Venturi, Miro},
title = {Expression of Serine/Threonine Protein-Kinases and Related Factors
in Normal Monkey and Human Retinas: The Mechanistic Understanding
of a CDK2 Inhibitor Induced Retinal Toxicity},
journal = {Toxicol Pathol},
year = {2007},
volume = {35},
pages = {972--983},
number = {7},
month = dec,
abstract = {Protein-kinase inhibitors are among the most advanced compounds in
development using the new drug discovery paradigm of developing small-molecule
drugs against specific molecular targets in cancer. After treatment
with a cyclin dependent kinase CDK2 inhibitor in monkey, histopathological
analysis of the eye showed specific cellular damage in the photoreceptor
layer. Since this CDK2 inhibitor showed activity also on other CDKs,
in order to investigate the mechanism of toxicity of this compound,
we isolated cones and rods from the retina of normal monkey and humans
by Laser Capture Microdissection. Using Real-Time PCR we first measured
the expression of cyclin dependent protein-kinases (CDK)1, 2, 4,
5, Glycogen synthase kinase 3{beta} (GSK3{beta}) and microtubule
associated protein TAU. We additionally verified the presence of
these proteins in monkey eye sections by immunohistochemistry and
immunofluorescence analysis and afterwards quantified GSK3{beta},
phospho-GSK3{beta} and TAU by Reverse Phase Protein Microarrays.
With this work we demonstrate how complementary gene expression and
protein-based technologies constitute a powerful tool for the understanding
of the molecular mechanism of a CDK2 inhibitor induced toxicity.
Moreover, this investigative approach is helpful to better understand
and characterize the mechanism of species-specific toxicities and
further support a rational, molecular mechanism-based safety assessment
in humans.},
url = {http://tpx.sagepub.com/cgi/content/abstract/35/7/972}
}
@ARTICLE{Satyanarayana2012,
author = {Satyanarayana, Ande and Klarmann, Kimberly D. and Gavrilova, Oksana
and Keller, Jonathan R.},
title = {Ablation of the transcriptional regulator Id1 enhances energy expenditure,
increases insulin sensitivity, and protects against age and diet
induced insulin resistance, and hepatosteatosis},
journal = {FASEB J},
year = {2012},
volume = {26},
pages = {309-323},
number = {1},
abstract = {Obesity is a major health concern that contributes to the development
of diabetes, hyperlipidemia, coronary artery disease, and cancer.
Id proteins are helix-loop-helix transcription factors that regulate
the proliferation and differentiation of cells from multiple tissues,
including adipocytes. We screened mouse tissues for the expression
of Id1 and found that Id1 protein is highly expressed in brown adipose
tissue (BAT) and white adipose tissue (WAT), suggesting a role for
Id1 in adipogenesis and cell metabolism. Id1-/- mice are viable but
show a significant reduction in fat mass (P<0.005) over the life
of the animal that was not due to decreased number of adipocytes.
Analysis of Id1-/- mice revealed higher energy expenditure, increased
lipolysis, and fatty acid oxidation, resulting in reduced triglyceride
accumulation in WAT compared to Id1+/+ mice. Serum levels of triglycerides
(193.9{+/-}32.2 vs. 86.5{+/-}33.8, P<0.0005), cholesterol (189.4{+/-}33.8
vs. 110.6{+/-}8.23, P<0.0005) and leptin (1263{+/-}835 vs. 222{+/-}260,
P<0.005) were significantly lower in aged Id1-/- mice compared to
Id1+/+ mice. Id1-deficient mice have higher resting (P<0.005) and
total (P<0.05) O2 consumption and lower respiratory exchange ratio
(P<0.005), confirming that Id1-/- mice use a higher proportion of
lipid as an energy source for the increased energy expenditure. The
expression of PGC1 and UCP1 were 2- to 3-fold up-regulated in Id1-/-
BAT, suggesting that loss of Id1 increases thermogenesis. As a consequence
of higher energy expenditure and reduced fat mass, Id1-/- mice displayed
enhanced insulin sensitivity. Id1 deficiency protected mice against
age- and high-fat-diet-induced adiposity, insulin resistance, and
hepatosteatosis. Our findings suggest that Id1 plays a critical role
in the regulation of energy homeostasis and could be a potential
target in the treatment of insulin resistance and fatty liver disease.--Satyanarayana,
A., Klarmann, K. D., Gavrilova, l O., Keller, J. R. Ablation of the
transcriptional regulator Id1 enhances energy expenditure, increases
insulin sensitivity, and protects against age and diet-induced insulin
resistance and hepatosteatosis.},
doi = {10.1096/fj.11-190892},
eprint = {http://www.fasebj.org/cgi/reprint/26/1/309.pdf},
url = {http://www.fasebj.org/cgi/content/abstract/26/1/309}
}
@ARTICLE{Saul2010,
author = {Saul, Katherine E. and Koke, Joseph R. and García, Dana M.},
title = {Activating transcription factor 3 (ATF3) expression in the neural
retina and optic nerve of zebrafish during optic nerve regeneration},
journal = {Comparative Biochemistry and Physiology - Part A: Molecular \& Integrative
Physiology},
year = {2010},
volume = {155},
pages = {172--182},
number = {2},
month = feb,
abstract = {Fish, unlike mammals, can regenerate axons in the optic nerve following
optic nerve injury. We hypothesized that using microarray analysis
to compare gene expression in fish which had experienced optic nerve
lesion to fish which had undergone a similar operation but without
optic nerve injury would reveal genes specifically involved in responding
to optic nerve injury (including repair), reducing detection of genes
involved in the general stress and inflammatory responses. We discovered
120 genes were significantly (minimally two-fold with a P-value <= 0.05)
differentially expressed (up or down) at one or more time point.
Among these was ATF3, a member of the cAMP-response element binding
protein family. Work by others has indicated that elevated cAMP could
be important in axon regeneration. We investigated ATF3 expression
further by qRT-PCR, in situ hybridization and immunohistochemistry
and found ATF3 expression is significantly upregulated in the ganglion
cell layer of the retina, the nerve fiber layer and the optic nerve
of the injured eye. The upregulation in retina is detectable by qRT-PCR
by 24 h after injury, at which time ATF-3 mRNA levels are 8-fold
higher than in retinas from sham-operated fish. We conclude ATF3
may be an important mediator of optic nerve regeneration-promoting
gene expression in fish, a role which merits further investigation.},
issn = {1095-6433},
keywords = {Optic nerve regeneration, Zebrafish, ATF3, Differential gene expression,
cAMP, Oligodendrocytes, Astrocytes, Retinal ganglion cells},
url = {http://www.sciencedirect.com/science/article/B6VNH-4XMD5RC-4/2/d2767b8b0da1ea301b74962960cc9206}
}
@ARTICLE{Saulnier2007,
author = {Saulnier, Delphine M. A. and Molenaar, Douwe and de Vos, Willem M.
and Gibson, Glenn R. and Kolida, Sofia},
title = {Identification of Prebiotic Fructooligosaccharide Metabolism in Lactobacillus
plantarum WCFS1 through Microarrays},
journal = {Appl. Envir. Microbiol.},
year = {2007},
volume = {73},
pages = {1753--1765},
number = {6},
month = mar,
abstract = {Short-chain fructooligosaccharides (scFOS) and other prebiotics are
used to selectively stimulate the growth and activity of lactobacilli
and bifidobacteria in the colon. However, there is little information
on the mechanisms whereby prebiotics exert their specific effects
upon such microorganisms. To study the genomic basis of scFOS metabolism
in Lactobacillus plantarum WCFS1, two-color microarrays were used
to screen for differentially expressed genes when grown on scFOS
compared to glucose (control). A significant up-regulation (8- to
60-fold) was observed with a set of only five genes located in a
single locus and predicted to encode a sucrose phosphoenolpyruvate
transport system (PTS), a {beta}-fructofuranosidase, a fructokinase,
an {alpha}-glucosidase, and a sucrose operon repressor. Several other
genes were slightly overexpressed, including pyruvate dehydrogenase.
For the latter, no detectable activity in L. plantarum under various
growth conditions has been previously reported. A mannose-PTS likely
to encode glucose uptake was 50-fold down-regulated as well as, to
a lower extent, other PTSs. Chemical analysis of the different moieties
of scFOS that were depleted in the growth medium revealed that the
trisaccharide 1-kestose present in scFOS was preferentially utilized,
in comparison with the tetrasaccharide nystose and the pentasaccharide
fructofuranosylnystose. The main end products of scFOS fermentation
were lactate and acetate. This is the first example in lactobacilli
of the association of a sucrose PTS and a {beta}-fructofuranosidase
that could be used for scFOS degradation.},
url = {http://aem.asm.org/cgi/content/abstract/73/6/1753}
}
@ARTICLE{Saurat2012,
author = {Saurat, Jean-Hilaire and Kaya, Guerkan and Saxer-Sekulic, Nikolina
and Pardo, Bruno and Becker, Minerva and Fontao, Lionel and Mottu,
Florence and Carraux, Pierre and Pham, Xuan-Cuong and Barde, Caroline
and Fontao, Fabienne and Zennegg, Markus and Schmid, Peter and Schaad,
Olivier and Descombes, Patrick and Sorg, Olivier},
title = {The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning
of Victor Yushchenko},
journal = {Toxicol. Sci.},
year = {2012},
volume = {125},
pages = {310-317},
number = {1},
abstract = {Several million people are exposed to dioxin and dioxin-like compounds,
primarily through food consumption. Skin lesions historically called
"chloracne" are the most specific sign of abnormal dioxin exposure
and classically used as a key marker in humans. We followed for 5
years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD), at a single oral dose of 5 million-fold more than the accepted
daily exposure in the general population. We adopted a molecular
medicine approach, aimed at identifying appropriate therapy. Skin
lesions, which progressively covered up to 40% of the body surface,
were found to be hamartomas, which developed parallel to a complete
and sustained involution of sebaceous glands, with concurrent transcriptomic
alterations pointing to the inhibition of lipid metabolism and the
involvement of bone morphogenetic proteins signaling. Hamartomas
created a new compartment that concentrated TCDD up to 10-fold compared
with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome
P450 1A1, thus representing a potentially significant source of enzymatic
activity, which may add to the xenobiotic metabolism potential of
the classical organs such as the liver. This historical case provides
a unique set of data on the human tissue response to dioxin for the
identification of new markers of exposure in human populations. The
herein discovered adaptive cutaneous response to TCDD also points
to the potential role of the skin in the metabolism of food xenobiotics.},
doi = {10.1093/toxsci/kfr223},
eprint = {http://toxsci.oxfordjournals.org/cgi/reprint/125/1/310.pdf},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/125/1/310}
}
@ARTICLE{Sauret-Gueto2006,
author = {Sauret-Gueto, Susanna and Botella-Pavia, Patricia and Flores-Perez,
Ursula and Martinez-Garcia, Jaime F. and San Roman, Carolina and
Leon, Patricia and Boronat, Albert and Rodriguez-Concepcion, Manuel},
title = {Plastid Cues Posttranscriptionally Regulate the Accumulation of Key
Enzymes of the Methylerythritol Phosphate Pathway in Arabidopsis},
journal = {Plant Physiology},
year = {2006},
volume = {141},
pages = {75--84},
number = {1},
month = may,
abstract = {Plastid isoprenoids (including hormones and photosynthetic pigments)
are essential for plant growth and development, but relatively little
is known of how the production of their metabolic precursors via
the recently elucidated methylerythritol phosphate (MEP) pathway
is regulated. We have identified an Arabidopsis (Arabidopsis thaliana)
mutant that survives an otherwise lethal block of the MEP pathway
with fosmidomycin (FSM). In rif10 (resistant to inhibition with FSM
10) plants, the accumulation of flux-controlling enzymes of the pathway
is posttranscriptionally up-regulated. Strikingly, this phenotype
is linked to a lower accumulation of plastidial isoprenoid pigments
such as chlorophylls and carotenoids, resulting in mutant plants
that are paler and smaller than the wild type. The rif10 mutant is
impaired in plastid RNA processing due to a T-DNA insertion in the
coding region of the At3g03710 gene encoding the chloroplast-targeted
exoribonuclease polyribonucleotide phosphorylase. FSM resistance
and other rif10-like phenotypes were also observed in wild-type Arabidopsis,
tomato (Lycopersicon esculentum), and rice (Oryza sativa) seedlings
grown in the presence of sublethal concentrations of chloramphenicol
(an inhibitor of protein synthesis in plastids). By contrast, treatment
with norflurazon (an inhibitor of carotenoid biosynthesis causing
a similar pale cotyledon phenotype) did not result in FSM resistance.
Together, the results support that plastome-encoded proteins are
involved in negatively regulating the posttranscriptional accumulation
of specific nuclear-encoded MEP pathway enzymes in chloroplasts.
Regulation of the MEP pathway by a mechanism dependent on plastid
cues might function under physiological conditions to finely adjust
plastidial isoprenoid biosynthesis to the metabolic capabilities
or requirements of plastids.},
url = {http://www.plantphysiol.org/cgi/content/abstract/141/1/75}
}
@ARTICLE{Savagner2003,
author = {Savagner, Frédérique and Mirebeau, Delphine and Jacques, Caroline
and Guyetant, Serge and Morgan, Catherine and Franc, Brigitte and
Reynier, Pascal and Malthièry, Yves},
title = {PGC-1-related coactivator and targets are upregulated in thyroid
oncocytoma},
journal = {Biochemical and Biophysical Research Communications},
year = {2003},
volume = {310},
pages = {779--784},
number = {3},
month = oct,
abstract = {Thyroid oncocytomas are tumors characterized by dense mitochondrial
accumulation, the cause of which is currently unknown. Members of
the PGC-1 coactivator family have been identified as important mediators
of mitochondrial biogenesis because of their ability to activate
nuclear genes encoding mitochondrial proteins. We have investigated
the influence of the PGC-1 related coactivator (PRC) on the high
mitochondrial content observed in oncocytoma by quantifying the transcripts
of PRC, the nuclear respiratory factor 1 (NRF-1) and the mitochondrial
transcription factor A (TFAM), in 30 oncocytic tumors and corresponding
normal tissues. The three genes studied were found to be significantly
overexpressed in thyroid oncocytomas, concomitantly with an increase
in cytochrome oxidase activity and mitochondrial DNA (mtDNA) content.
However, no mtDNA variant in the D-loop region appeared to be involved
in oncocytic development. We conclude that overexpression of the
PRC pathway is responsible for mitochondrial proliferation in the
context of thyroid oncocytoma.},
issn = {0006-291X},
keywords = {Thyroid, Oncocytoma, Mitochondria, PGC-1 related coactivator, Tumor},
url = {http://www.sciencedirect.com/science/article/B6WBK-49M6MN8-F/2/51cc0633fc1f2c4fb06ed22631cfdaf0}
}
@ARTICLE{Savard2008,
author = {Savard, Martin and Barbaz, David and Bélanger, Simon and Müller-Esterl,
Werner and Bkaily, Ghassan and D'orléans-Juste, Pedro and Coté,
Jérôme and Bovenzi, Veronica and Gobeil, Fernand},
title = {Expression of endogenous nuclear bradykinin B2 receptors mediating
signaling in immediate early gene activation},
journal = {J. Cell. Physiol.},
year = {2008},
volume = {216},
pages = {234--244},
number = {1},
abstract = {Abstract 10.1002/jcp.21398.abs Bradykinin (BK) represents a pro-inflammatory
mediator that partakes in many inflammatory diseases. The mechanism
of action of BK is thought to be primarily mediated by specific cell
surface membrane B2 receptors (B2Rs). Some evidence has suggested,
however, the existence of an intracellular/nuclear B2R population.
Whether these receptors are functional and contribute to BK signaling
remains to be determined. In this study, by mean of Western blotting,
3D-confocal microscopy, receptor autoradiography and radioligand
binding analysis, we showed that plasma membrane and highly purified
nuclei from isolated rat hepatocytes contain specific B2R that bind
BK. The results depicting B2R nuclear expression in isolated nuclear
organelles were reproduced in situ on hepatic sections by immunogold
labeling and transmission electron microscopy. Functional tests on
single nuclei, by means of confocal microscopy and the calcium-sensitive
probe fluo-4AM, showed that BK induces concentration-dependent transitory
mobilization of nucleoplasmic calcium; these responses were blocked
by B2R antagonist HOE 140, not by the B1R antagonist R954 and, were
also found in wild-type C57/Bl6 mice, but not in B2R-KO mice. In
isolated nuclei, BK elicited activation/phosphorylation of Akt, acetylation
of histone H3 and ensuing pro-inflammatory iNOS gene induction as
determined by Western blot and RT-PCR. ChIP assay confirmed binding
of acetylated-histone H3 complexes, but not B2R, to promoter region
of iNOS gene suggesting that B2R-mediated gene expression is bridged
with accessory downstream effectors. This study discloses a previously
undescribed mechanism in BK-induced transcriptional events, via intracrine
B2R-mediated signaling, occurring in rat autologous hepatic cells.
J. Cell. Physiol. 216: 234–244, 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.21398}
}
@ARTICLE{Savci-Heijink2009,
author = {Savci-Heijink, Cemile Dilara and Kosari, Farhad and Aubry, Marie-Christine
and Caron, Bolette L. and Sun, Zhifu and Yang, Ping and Vasmatzis,
George},
title = {The Role of Desmoglein-3 in the Diagnosis of Squamous Cell Carcinoma
of the Lung},
journal = {Am. J. Pathol.},
year = {2009},
volume = {174},
pages = {1629--1637},
number = {5},
month = may,
abstract = {Results from several microarray-based studies have led to the identification
of up-regulated expression levels of the DSG3 gene in pulmonary squamous
cell carcinomas (SQCCs). The purpose of this study was to determine
the role of DSG3 expression in the diagnosis of SQCCs of the lung
and to compare DSG3 with p63, CK5, and CK6, as markers of squamous
cell differentiation. Expression of DSG3 mRNA was evaluated in bulk
laser capture microdissection-derived microarray data and by quantitative
reverse transcription PCR on both SQCCs and adenocarcinomas. Expression
levels of p63, CK5, and CK6 were evaluated in microarray data from
the same set. An immunohistochemical study using antibodies directed
against DSG3, p63, and CK5/6 was also performed. DSG3 was over-expressed
in SQCCs but had very limited expression in both adenocarcinomas
and non-neoplastic lungs. The microarray data showed that DSG3 had
a sensitivity and specificity of 88% and 98%, respectively, in detecting
SQCC versus adenocarcinoma. In comparison, sensitivity and specificity
was 92% and 82% for p63, and 85% and 96% for CK5, respectively. The
correlation coefficient between the microarray and immunohistochemical
data for these genes was greater than or equal to 0.9. Using immunohistochemistry,
sensitivity and specificity of DSG3 for lung cancers were 98% and
99%, respectively. Therefore, DSG3 can be a useful ancillary marker
to separate SQCC from other subtypes of lung cancer.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/174/5/1629}
}
@ARTICLE{Savignac2010,
author = {Savignac, Magali and Mellstrom, Britt and Bebin, Anne-Gaelle and
Oliveros, Juan C. and Delpy, Laurent and Pinaud, Eric and Naranjo,
Jose R.},
title = {Increased B Cell Proliferation and Reduced Ig Production in DREAM
Transgenic Mice},
journal = {J. Immunol.},
year = {2010},
volume = {185},
pages = {7527--7536},
number = {12},
month = dec,
abstract = {DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly
expressed in immune cells. Transgenic mice expressing a dominant
active DREAM mutant show reduced serum Ig levels. In vitro assays
show that reduced Ig secretion is an intrinsic defect of transgenic
B cells that occurs without impairment in plasma cell differentiation,
class switch recombination, or Ig transcription. Surprisingly, transgenic
B cells show an accelerated entry in cell division. Transcriptomic
analysis of transgenic B cells revealed that hyperproliferative B
cell response could be correlated with a reduced expression of Klf9,
a cell-cycle regulator. Pulse-chase experiments demonstrated that
the defect in Ig production is associated with reduced translation
rather than with increased protein degradation. Importantly, transgenic
B cells showed reduced expression of the Eif4g3 gene, which encodes
a protein related to protein translation. Our results disclose, to
our knowledge, a novel function of DREAM in proliferation and Ig
synthesis in B lymphocytes.},
comment = {10.4049/jimmunol.1000152},
url = {http://www.jimmunol.org/cgi/content/abstract/185/12/7527}
}
@ARTICLE{Savino2007,
author = {Savino, Maria and Garrubba, Maria and Parrella, Paola and Baorda,
Filomena and Copetti, Massimiliano and Murgo, Roberto and Zelante,
Leopoldo and Carella, Massimo and Valori, Vanna Maria and Santini,
Stefano Angelo},
title = {Development of real-time quantitative reverse transcription-PCR for
Her2 detection in peripheral blood from patients with breast cancer},
journal = {Clinica Chimica Acta},
year = {2007},
volume = {384},
pages = {52--56},
number = {1-2},
month = sep,
abstract = {Background Amplification of the Her2neu oncogene is a well known indicator
of poor prognosis in breast cancer patients. The implementation into
the clinical setting of therapeutical strategies directly targeting
the Her2neu gene product, has create the need for the development
of non-invasive analytical techniques in order to monitoring minimal
residual disease and response to the treatment.Methods To detect
the expression of Her2neu mRNA in peripheral blood, we developed
a specific real-time quantitative reverse transcription-PCR (QPCR)
assay. The analyses were performed on blood samples obtained from
30 breast cancer patients positive for Her2neu overexpression by
immunohistochemical analysis (IHC), 10 breast cancer patients negative
for Her2neu overexpression, and 24 healthy controls.Results Her2neu
positive tumors showed a significant increase in mRNA transcripts
as compared with both healthy controls (n = 24) and Her2neu negative
patients (n = 10). After establishing a cut-off value, 18 out of
the 30 Her2neu positive patient scored positive for Her2neu expression,
whereas only 1 out of the 10 Her2neu negative patients was weakly
positive.Conclusions Her2neu QPCR is suitable method for Her2neu
overexpression detection in peripheral blood from clinical samples
of breast cancer patients. QPCR could be used to identify breast
cancer patients with poor prognosis and for monitoring response to
the therapy.},
issn = {0009-8981},
keywords = {Breast cancer, Tumoral markers, HER2, Quantitative PCR, IHC},
url = {http://www.sciencedirect.com/science/article/B6T57-4NX2NM2-1/2/bafa21fb88075c7f258d72ae89b2cd12}
}
@ARTICLE{Saviozzi2009,
author = {Saviozzi, Silvia and Ceppi, Paolo and Novello, Silvia and Ghio, Paolo
and Lo Iacono, Marco and Borasio, Piero and Cambieri, Alberto and
Volante, Marco and Papotti, Mauro and Calogero, Raffaele A. and Scagliotti,
Giorgio V.},
title = {Non-Small Cell Lung Cancer Exhibits Transcript Overexpression of
Genes Associated with Homologous Recombination and DNA Replication
Pathways},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {3390--3396},
number = {8},
month = apr,
abstract = {Genes involved in DNA repair and replication have been recently investigated
as predictive markers of response to chemotherapy in non-small cell
lung cancer (NSCLC). However, few data on the expression of these
genes in tumor compared with corresponding normal lung are available.
The aim of this study was to evaluate differential mRNA levels of
22 DNA repair genes of five different DNA repair pathways: direct,
base excision, nucleotide excision (NER), double-strand break (DSBR),
and postreplicative repair. In addition, six genes involved in DNA
replication (REP) and three telomere maintenance genes were investigated.
Total RNAs extracted from fresh-frozen tumors and corresponding normal
tissues of 50 consecutive chemo-naive resected NSCLC patients were
analyzed. Transcript levels were quantified by real-time PCR. A significant
overexpression was detected in 20 of 30 (67%) genes, mostly belonging
to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were
significantly underexpressed. For 7 of 30 (23%) genes, mostly belonging
to NER pathway, no significant difference between paired tumor and
normal samples was observed. Transcript overexpression of DSBR and
REP genes was significantly higher in poorly differentiated carcinomas
and DSBR levels were higher in men compared with women. The transcriptional
overexpression of four genes (XRCC5, TOP3B, TYMS, and UNG) showed
significant correlation with a shorter patients' outcome at the univariate,
whereas only stage of disease appeared as an independent factor affecting
prognosis, as assessed by multivariate analysis. In conclusion, genes
belonging to DNA repair/replication pathways are overexpressed in
NSCLC and are associated with a more aggressive phenotype. [Cancer
Res 2009;69(8):3390-6]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/8/3390}
}
@ARTICLE{Savola2009,
author = {Savola, Suvi and Klami, Arto and Tripathi, Abhishek and Niini, Tarja
and Serra, Massimo and Picci, Piero and Kaski, Samuel and Zambelli,
Diana and Scotlandi, Katia and Knuutila, Sakari},
title = {Combined use of expression and CGH arrays pinpoints novel candidate
genes in Ewing sarcoma family of tumors},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {17},
number = {1},
abstract = {BACKGROUND:Ewing sarcoma family of tumors (ESFT), characterized by
t(11;22)(q24;q12), is one of the most common tumors of bone in children
and young adults. In addition to EWS/FLI1 gene fusion, copy number
changes are known to be significant for the underlying neoplastic
development of ESFT and for patient outcome. Our genome-wide high-resolution
analysis aspired to pinpoint genomic regions of highest interest
and possible target genes in these areas.METHODS:Array comparative
genomic hybridization (CGH) and expression arrays were used to screen
for copy number alterations and expression changes in ESFT patient
samples. A total of 31 ESFT samples were analyzed by aCGH and in
16 patients DNA and RNA level data, created by expression arrays,
was integrated. Time of the follow-up of these patients was 5–192
months. Clinical outcome was statistically evaluated by Kaplan-Meier/Logrank
methods and RT-PCR was applied on 42 patient samples to study the
gene of the highest interest.RESULTS:Copy number changes were detected
in 87% of the cases. The most recurrent copy number changes were
gains at 1q, 2, 8, and 12, and losses at 9p and 16q. Cumulative event
free survival (ESFT) and overall survival (OS) were significantly
better (P < 0.05) for primary tumors with three or less copy number
changes than for tumors with higher number of copy number aberrations.
In three samples copy number imbalances were detected in chromosomes
11 and 22 affecting the FLI1 and EWSR1 loci, suggesting that an unbalanced
t(11;22) and subsequent duplication of the derivative chromosome
harboring fusion gene is a common event in ESFT. Further, amplifications
on chromosomes 20 and 22 seen in one patient sample suggest a novel
translocation type between EWSR1 and an unidentified fusion partner
at 20q. In total 20 novel ESFT associated putative oncogenes and
tumor suppressor genes were found in the integration analysis of
array CGH and expression data. Quantitative RT-PCR to study the expression
levels of the most interesting gene, HDGF, confirmed that its expression
was higher than in control samples. However, no association between
HDGF expression and patient survival was observed.CONCLUSION:We conclude
that array CGH and integration analysis proved to be effective methods
to identify chromosome regions and novel target genes involved in
the tumorigenesis of ESFT.},
doi = {10.1186/1471-2407-9-17},
issn = {1471-2407},
pubmedid = {19144156},
url = {http://www.biomedcentral.com/1471-2407/9/17}
}
@ARTICLE{Sawada2005,
author = {Sawada, Hiroshi and Takami, Kenji and Asahi, Satoru},
title = {A Toxicogenomic Approach to Drug-Induced Phospholipidosis: Analysis
of Its Induction Mechanism and Establishment of a Novel in Vitro
Screening System},
journal = {Toxicol. Sci.},
year = {2005},
volume = {83},
pages = {282--292},
number = {2},
month = feb,
abstract = {Phospholipidosis is a lipid storage disorder in which excess phospholipids
accumulate within cells. Some cationic amphiphilic compounds are
known to have the potential to induce phospholipidosis. This study
was undertaken to examine the molecular mechanisms that contribute
to the development of phospholipidosis and to identify specific markers
that might form the basis of an in vitro screening test. Specifically,
we performed a large-scale gene expression analysis using DNA microarrays
on human hepatoma HepG2 cells after they were treated with each of
12 compounds known to induce phospholipidosis. In electron microscopy,
HepG2 cells developed lamellar myelin-like bodies in their lysosomes,
the characteristic change of phospholipidosis, after treatment with
these compounds for 72 h. DNA microarray analysis performed 6 and
24 h after treatment showed alterations in gene expression reflecting
the inhibition of lysosomal phospholipase activity and lysosomal
enzyme transport, and the induction of phospholipid and cholesterol
biosynthesis. Seventeen genes that showed a similar expression profile
following treatment were selected as candidate markers. Real-time
PCR analysis confirmed that 12 gene markers showed significant concordance
with lamellar myelin-like body formation. Furthermore, the average
fold change values of these markers correlated well with the magnitude
of this pathological change. In conclusion, microarray analysis revealed
that factors such as alterations in lysosomal function and cholesterol
metabolism were involved in the induction of phospholipidosis. Furthermore,
comprehensive gene expression analysis enabled us to identify biomarkers
of this condition that we then used to develop a rapid and sensitive
in vitro screening test for drug-induced phospholipidosis.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/83/2/282}
}
@ARTICLE{Sawada2006,
author = {Sawada, Hiroshi and Taniguchi, Keiko and Takami, Kenji},
title = {Improved toxicogenomic screening for drug-induced phospholipidosis
using a multiplexed quantitative gene expression ArrayPlate assay},
journal = {Toxicology in Vitro},
year = {2006},
volume = {20},
pages = {1506--1513},
number = {8},
month = dec,
abstract = {We previously showed that a toxicogenomics analysis of drug-induced
phospholipidosis enabled the identification of 12 specific gene markers
and the establishment of an in vitro real-time PCR screening assay
for the assessment of the phospholipidosis-inducing potential of
compounds. The purpose of this study was to transfer our PCR-based
assay into a 96-well microplate-based multiple mRNAs measuring assay
(ArrayPlate(TM) assay) in order to increase throughput. Specifically,
we determined the expression of the 12 marker genes using real-time
PCR and ArrayPlate in human hepatoma HepG2 cells that were treated
for 24 h with each of amiodarone and 80 proprietary compounds. The
following three performance criteria were satisfied in the ArrayPlate
analysis: 1. Sensitivity--the expression of mRNA for all target genes
was detected at quantifiable levels. 2. Repeatability--signal intensities
and fold change values of each marker gene were highly repeatable.
3. Correlation--fold change values and their average values, which
were used as indices of phospholipidosis induction potential, showed
apparent correlation between the ArrayPlate and real-time PCR assays.
Thus, the in vitro screening assay for compound-induced phospholipidosis
should be transferable from a PCR-based assay to the higher-throughput
ArrayPlate-based method.},
issn = {0887-2333},
keywords = {Drug-induced phospholipidosis, In vitro screening assay, ArrayPlate
technology, Real-time PCR, Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/B6TCP-4K3N5R2-2/2/30f0a2ee16d13909e37ddae5657a2c9f}
}
@ARTICLE{Sawada2009,
author = {Sawada, Jun and Yamashita, Takenari and Aizawa, Hitoshi and Aburakawa,
Yoko and Hasebe, Naoyuki and Kwak, Shin},
title = {Effects of antidepressants on GluR2 Q/R site-RNA editing in modified
HeLa cell line},
journal = {Neuroscience Research},
year = {2009},
volume = {64},
pages = {251--258},
number = {3},
month = jul,
abstract = {Marked reduction of RNA editing at the glutamine (Q)/arginine (R)
site of the glutamate receptor subunit type 2 (GluR2) in motor neurons
may be a contributory cause of neuronal death specifically in sporadic
ALS. It has been shown that deregulation of RNA editing of several
mRNAs plays a causative role in diseases of the central nervous system
such as depression. We analyzed the effects of eight antidepressants
on GluR2 Q/R site-RNA editing in a modified HeLa cell line that stably
expresses half-edited GluR2 pre-mRNA. We also measured changes in
RNA expression levels of adenosine deaminase acting on RNA type 2
(ADAR2), the specific RNA editing enzyme of the GluR2 Q/R site, and
GluR2, in order to assess the molecular mechanism causing alteration
of this site-editing. The editing efficiency at the GluR2 Q/R site
was significantly increased after treatment with seven out of eight
antidepressants at a concentration of no more than 10 [mu]M for 24 h.
The relative abundance of ADAR2 mRNA to GluR2 pre-mRNA or to [beta]-actin
mRNA was increased after treatment with six of the effective antidepressants,
whereas it was unchanged after treatment with milnacipran. Our results
suggest that antidepressants have the potency to enhance GluR2 Q/R
site-editing by either upregulating the ADAR2 mRNA expression level
or other unidentified mechanisms. It may be worth investigating the
in vivo efficacy of antidepressants with a specific therapeutic strategy
for sporadic ALS in view.},
issn = {0168-0102},
keywords = {AMPA receptor, GluR2, RNA editing, Adenosine deaminase acting on RNA
type 2 (ADAR2), Antidepressant, Amyotrophic lateral sclerosis (ALS)},
url = {http://www.sciencedirect.com/science/article/B6T0H-4VXDTP9-2/2/6c04c14ef6c35353b632bf049889ac27}
}
@ARTICLE{Sawaki2009,
author = {Sawaki, Yoshiharu and Iuchi, Satoshi and Kobayashi, Yasufumi and
Kobayashi, Yuriko and Ikka, Takashi and Sakurai, Nozomu and Fujita,
Miki and Shinozaki, Kazuo and Shibata, Daisuke and Kobayashi, Masatomo
and Koyama, Hiroyuki},
title = {STOP1 Regulates Multiple Genes That Protect Arabidopsis from Proton
and Aluminum Toxicities},
journal = {Plant Physiology},
year = {2009},
volume = {150},
pages = {281--294},
number = {1},
month = may,
abstract = {The Arabidopsis (Arabidopsis thaliana) mutant stop1 (for sensitive
to proton rhizotoxicity1) carries a missense mutation at an essential
domain of the histidine-2-cysteine-2 zinc finger protein STOP1. Transcriptome
analyses revealed that various genes were down-regulated in the mutant,
indicating that STOP1 is involved in signal transduction pathways
regulating aluminum (Al)- and H+-responsive gene expression. The
Al hypersensitivity of the mutant could be caused by down-regulation
of AtALMT1 (for Arabidopsis ALUMINUM-ACTIVATED MALATE TRANSPORTER1)
and ALS3 (ALUMINUM-SENSITIVE3). This hypothesis was supported by
comparison of Al tolerance among T-DNA insertion lines and a transgenic
stop mutant carrying cauliflower mosaic virus 35S::AtALMT1. All T-DNA
insertion lines of STOP1, AtALMT1, and ALS3 were sensitive to Al,
but introduction of cauliflower mosaic virus 35S::AtALMT1 did not
completely restore the Al tolerance of the stop1 mutant. Down-regulation
of various genes involved in ion homeostasis and pH-regulating metabolism
in the mutant was also identified by microarray analyses. CBL-INTERACTING
PROTEIN KINASE23, regulating a major K+ transporter, and a sulfate
transporter, SULT3;5, were down-regulated in the mutant. In addition,
integral profiling of the metabolites and transcripts revealed that
pH-regulating metabolic pathways, such as the{gamma} -aminobutyric
acid shunt and biochemical pH stat pathways, are down-regulated in
the mutant. These changes could explain the H+ hypersensitivity of
the mutant and would make the mutant more susceptible in acid soil
stress than other Al-hypersensitive T-DNA insertion lines. Finally,
we showed that STOP1 is localized to the nucleus, suggesting that
the protein regulates the expression of multiple genes that protect
Arabidopsis from Al and H+ toxicities, possibly as a transcription
factor.},
url = {http://www.plantphysiol.org/cgi/content/abstract/150/1/281}
}
@ARTICLE{Sawicka2005,
author = {Sawicka, Elzbieta and Dubois, Gerald and Jarai, Gabor and Edwards,
Matthew and Thomas, Matthew and Nicholls, Andy and Albert, Rainer
and Newson, Catherine and Brinkmann, Volker and Walker, Christoph},
title = {The Sphingosine 1-Phosphate Receptor Agonist FTY720 Differentially
Affects the Sequestration of CD4+/CD25+ T-Regulatory Cells and Enhances
Their Functional Activity},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {7973--7980},
number = {12},
month = dec,
abstract = {The sphingosine 1-phosphate (S1P) receptor agonist FTY720 is well
known for its immunomodulatory activity, sequestering lymphocytes
from blood and spleen into secondary lymphoid organs and thereby
preventing their migration to sites of inflammation. Because inflammation
is critically dependent on a balance between Ag-specific Th/effector
cells and T-regulatory cells, we investigated the effect of FTY720
on T-regulatory cell trafficking and functional activity. An increased
number of CD4+/CD25+ T cells was found in blood and spleens of FTY720-treated
mice, and transfer of these cells resulted in a significantly more
pronounced accumulation in spleens but not lymph nodes after treatment,
suggesting that this compound differentially affects the homing properties
of T-regulatory cells compared with other T cell subsets. Indeed,
CD4+/CD25+ T cells express lower levels of S1P1 and S1P4 receptors
and demonstrate a reduced chemotactic response to S1P. Moreover,
analysis of the functional response of FTY720-treated CD4+/CD25+
T cells revealed an increased suppressive activity in an in vitro
Ag-specific proliferation assay. This correlated with enhanced function
in vivo, with T-regulatory cells obtained from FTY720-treated mice
being able to suppress OVA-induced airway inflammation. Thus, FTY720
differentially affects the sequestration of T-regulatory cells and
importantly, increases the functional activity of T-regulatory cells,
suggesting that it may have disease-modifying potential in inflammatory
disorders.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/12/7973}
}
@ARTICLE{Sawiris2007,
author = {Sawiris, G. Peter and Becker, Kevin G. and Elliott, Ellen J. and
Moulden, Robert and Rohwer, Robert G.},
title = {Molecular analysis of bovine spongiform encephalopathy infection
by cDNA arrays},
journal = {J. Gen. Virol.},
year = {2007},
volume = {88},
pages = {1356--1362},
number = {4},
month = apr,
abstract = {Here, the first cDNA array analysis of differential gene expression
in bovine spongiform encephalopathy (BSE) is reported, using a spotted
cDNA array platform representing nearly 17 000 mouse genes. Array
analysis identified 296 gene candidates for differential expression
in brain tissue from VM mice in late-stage infection with the 301V
strain of BSE, compared with brain tissue from normal, age-matched
VM mice. Real-time PCR confirmed differential expression of 25 of
31 genes analysed. Some of the genes identified by array analysis
as being expressed differentially are associated with ubiquitin/proteasome
function, lysosomal function, molecular chaperoning of protein folding
or apoptosis. Other genes are involved in calcium ion binding/homeostasis,
zinc ion binding/homeostasis or regulation of transcription. Principal-component
analysis shows that the global gene-expression profiles of the BSE-infected
samples have gene-expression signatures that are markedly different
from, and completely non-overlapping with, those obtained from the
normal controls.},
url = {http://vir.sgmjournals.org/cgi/content/abstract/88/4/1356}
}
@BOOK{Sayavedra-Soto2011,
title = {Dissecting Iron Uptake and Homeostasis in Nitrosomonas europaea},
publisher = {Academic Press},
year = {2011},
editor = {Klotz, Martin G.},
author = {Sayavedra-Soto, Luis A. and Vajrala, Neeraja and Arp, Daniel J.},
volume = {Volume 486},
pages = {403--428},
abstract = {The chemolithoautotroph Nitrosomonas europaea oxidizes about 25 mol
of NH3 for each mole of CO2 that is converted to biomass using an
array of heme and nonheme Fe-containing proteins. Hence mechanisms
of efficient iron (Fe) uptake and homeostasis are particularly important
for this Betaproteobacterium. Among nitrifiers, N. europaea has been
the most studied to date. Characteristics that make N. europaea a
suitable model to study Fe uptake and homeostasis are as follows:
(a) its sequenced genome, (b) its capability to grow relatively well
in 0.2 [mu]M Fe in the absence of heterologous siderophores, and
(c) its amenability to mutagenesis. In this chapter, we describe
the methodology we use in our laboratory to dissect Fe uptake and
homeostasis in the ammonia oxidizer N. europaea.},
booktitle = {Research on Nitrification and Related Processes, Part A},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/pii/B9780123812940000183}
}
@BOOK{Sayavedra-Soto2011a,
title = {Chapter Eighteen - Dissecting Iron Uptake and Homeostasis in Nitrosomonas
europaea},
publisher = {Academic Press},
year = {2011},
editor = {Martin G. Klotz},
author = {Luis A. Sayavedra-Soto and Neeraja Vajrala and Daniel J. Arp},
volume = {486},
pages = {403 - 428},
series = {Methods in Enzymology},
abstract = {Abstract The chemolithoautotroph Nitrosomonas europaea oxidizes about
25 mol of NH3 for each mole of CO2 that is converted to biomass using
an array of heme and nonheme Fe-containing proteins. Hence mechanisms
of efficient iron (Fe) uptake and homeostasis are particularly important
for this Betaproteobacterium. Among nitrifiers, N. europaea
has been the most studied to date. Characteristics that make N. europaea
a suitable model to study Fe uptake and homeostasis are as follows:
(a) its sequenced genome, (b) its capability to grow relatively well
in 0.2 μM Fe in the absence of heterologous siderophores, and
(c) its amenability to mutagenesis. In this chapter, we describe
the methodology we use in our laboratory to dissect Fe uptake and
homeostasis in the ammonia oxidizer N. europaea.},
booktitle = {Research on Nitrification and Related Processes, Part A},
doi = {10.1016/B978-0-12-381294-0.00018-3},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/pii/B9780123812940000183}
}
@ARTICLE{Sayi2009,
author = {Sayi, Ayca and Kohler, Esther and Hitzler, Iris and Arnold, Isabelle
and Schwendener, Reto and Rehrauer, Hubert and Muller, Anne},
title = {The CD4+ T Cell-Mediated IFN-{gamma} Response to Helicobacter Infection
Is Essential for Clearance and Determines Gastric Cancer Risk},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {7085--7101},
number = {11},
month = jun,
abstract = {Chronic infection with the bacterial pathogen Helicobacter pylori
is a risk factor for the development of gastric cancer, yet remains
asymptomatic in the majority of individuals. We report here that
the C57BL/6 mouse model of experimental infection with the closely
related Helicobacter felis recapitulates this wide range in host
susceptibility. Although the majority of infected animals develop
premalignant lesions such as gastric atrophy, compensatory epithelial
hyperplasia, and intestinal metaplasia, a subset of mice is completely
protected from preneoplasia. Protection is associated with a failure
to mount an IFN-{gamma} response to the infection and with a concomitant
high Helicobacter burden. Using a vaccine model as well as primary
infection and adoptive transfer models, we demonstrate that IFN-{gamma},
secreted predominantly by CD4+CD25- effector TH cells, is essential
for Helicobacter clearance, but at the same time mediates the formation
of preneoplastic lesions. We further provide evidence that IFN-{gamma}
triggers a common transcriptional program in murine gastric epithelial
cells in vitro and in vivo and induces their preferential transformation
to the hyperplastic phenotype. In summary, our data suggest a dual
role for IFN-{gamma} in Helicobacter pathogenesis that could be the
basis for the differential susceptibility to H. pylori-induced gastric
pathology in the human population.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/11/7085}
}
@ARTICLE{Sboner2010,
author = {Sboner, Andrea and Habegger, Lukas and Pflueger, Dorothee and Terry,
Stephane and Chen, David and Rozowsky, Joel and Tewari, Ashutosh
and Kitabayashi, Naoki and Moss, Benjamin and Chee, Mark and Demichelis,
Francesca and Rubin, Mark and Gerstein, Mark},
title = {FusionSeq: a modular framework for finding gene fusions by analyzing
paired-end RNA-sequencing data},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R104},
number = {10},
abstract = {We have developed FusionSeq to identify fusion transcripts from paired-end
RNA-sequencing. FusionSeq includes filters to remove spurious candidate
fusions with artifacts, such as misalignment or random pairing of
transcript fragments, and it ranks candidates according to several
statistics. It also has a module to identify exact sequences at breakpoint
junctions. FusionSeq detected known and novel fusions in a specially
sequenced calibration data set, including eight cancers with and
without known rearrangements.},
doi = {10.1186/gb-2010-11-10-r104},
issn = {1465-6906},
pubmedid = {20964841},
url = {http://genomebiology.com/2010/11/10/R104}
}
@ARTICLE{Scantland2011,
author = {Scantland, Sara and Grenon, Jean-Philippe and Desrochers, Marie-Hélène
and Sirard, Marc-André and Khandjian, Edward and Robert, Claude},
title = {Method to isolate polyribosomal mRNA from scarce samples such as
mammalian oocytes and early embryos},
journal = {BMC Developmental Biology},
year = {2011},
volume = {11},
pages = {8},
number = {1},
abstract = {BACKGROUND:Although the transcriptome of minute quantities of cells
can be profiled using nucleic acid amplification techniques, it remains
difficult to distinguish between active and stored messenger RNA.
Transcript storage occurs at specific stages of gametogenesis and
is particularly important in oogenesis as stored maternal mRNA is
used to sustain de novo protein synthesis during the early developmental
stages until the embryonic genome gets activated. In many cases,
stored mRNA can be several times more abundant than mRNA ready for
translation. In order to identify active mRNA in bovine oocytes,
we sought to develop a method of isolating very small amounts of
polyribosome mRNA.RESULTS:The proposed method is based on mixing
the extracted oocyte cytoplasm with a preparation of polyribosomes
obtained from a non-homologous source (Drosophila) and using sucrose
density gradient ultracentrifugation to separate the polyribosomes.
It involves cross-linking the non-homologous polyribosomes and neutralizing
the cross-linking agent. Using this method, we show that certain
stages of oocyte maturation coincide with changes in the abundance
of polyribosomal mRNA but not total RNA or poly(A). We also show
that the abundance of selected sequences matched changes in the corresponding
protein levels.CONCLUSIONS:We report here the successful use of a
method to profile mRNA present in the polyribosomal fraction obtained
from as little as 75 mammalian oocytes. Polyribosomal mRNA fractionation
thus provides a new tool for studying gametogenesis and early development
with better representation of the underlying physiological status.},
doi = {10.1186/1471-213X-11-8},
issn = {1471-213X},
pubmedid = {21324132},
url = {http://www.biomedcentral.com/1471-213X/11/8}
}
@ARTICLE{Scarpa2011,
author = {Scarpa, Marco and Bortolami, Marina and Cecchetto, Attilio and Faggian,
Diego and Kotsafti, Andromachi and Ruffolo, Cesare and Navaglia,
Filippo and Pozza, Anna and D'Incà, Renata and Plebani, Mario and
Sturniolo, Giacomo C. and Angriman, Imerio},
title = {Mucosal immune environment in colonic carcinogenesis: CD80 up-regulation
in colonic dysplasia in ulcerative colitis},
journal = {European Journal of Cancer},
year = {2011},
volume = {47},
pages = {611--619},
number = {4},
month = mar,
abstract = {Background In patients with ulcerative colitis (UC) the inconsistency
between the rate of dysplasia and actual cancer incidence suggests
the presence of an immunosurveillance mechanism. The aim of our study
was to analyse the expression of CD80 and CD86 during the different
stages of UC-associated and in non-inflammatory carcinogenesis.Patients
and methods Sixty-two patients affected with UC, UC with colonic
dysplasia, UC and cancer, colonic adenoma, or colonic cancer and
11 healthy subjects were enroled in our study. Tissue samples were
taken from surgical specimens during colonic resection or during
colonoscopy. Mucosal mRNA expression of CD80 and CD86 was quantified
with real time polymerase chain reaction (RT-PCR). CD80, CD86 and
p53 expressions and lamina propria mononuclear cell populations (CD3,
CD20 and CD68) were analysed by immunohistochemistry. Mucosal levels
of IL-1[beta], IL-2 and IFN-[gamma] were measured with immunometric
assays.Results Among UC patients, CD80 protein expression was higher
in those with dysplasia (p = 0.017). In non-inflammatory carcinogenesis
pathway CD80 protein and mRNA expressions were lower compared to
the corresponding steps in the UC pathway. CD80 expression was directly
correlated with the lamina propria mononuclear cell populations (T
and B lymphocytes and monocytes). CD80 protein, but not CD80 mRNA,
expression was significantly and directly correlated with IL-2 expression.Conclusion
CD80 resulted to be up-regulated in UC with dysplasia, while it was
down-regulated in cancer. CD80 mucosal levels correlate with lamina
propria T-cell and with IL-2 expression suggesting that it may elicit
an active role in the immunosurveillance mechanism.},
issn = {0959-8049},
keywords = {Colonic carcinogenesis, Immunosurveillance, Costimulatory molecules},
url = {http://www.sciencedirect.com/science/article/pii/S0959804910009950}
}
@ARTICLE{Scarpa2009,
author = {Scarpa, Marco and Bortolami, Marina and Morgan, Susan L. and Kotsafti,
Andromachi and Ferraro, Stefania and Ruffolo, Cesare and D'Incà,
Renata and Polese, Lino and Barollo, Michela and D'Amico, Davide
F. and Sturniolo, Giacomo C. and Angriman, Imerio},
title = {TGF-[beta]1 and IGF-1 Production and Recurrence of Crohn's Disease
After Ileo-Colonic Resection},
journal = {Journal of Surgical Research},
year = {2009},
volume = {152},
pages = {26--34},
number = {1},
month = mar,
abstract = {Background Recurrence after surgery is a major problem in the treatment
of Crohn's disease (CD). Alteration of healing processes may play
a role in this phenomenon. Transforming growth factor beta (TGF-[beta])
and insulin-like growth factor (IGF-1) have pro-fibrogenic properties
and are involved in wound-healing mechanisms. The aim of this study
was to assess their role in the CD recurrence after ileo-colonic
resection.Patients and methods Twenty patients with CD, who underwent
ileo-colonic resection in the period between 1999 and 2005, were
enrolled in this study. Tissue samples were obtained from macroscopically
diseased and healthy ileum. The TGF-[beta]1 and IGF-1 mRNAs were
quantified by real-time polymerase chain reaction using glyceraldehyde
3-phosphate dehydrogenase as the housekeeping gene. Histological
severity of the disease was assessed to quantify the ileal inflammation.
Patients' follow-up was investigated. Comparisons and correlations
were carried out with nonparametric tests and survival analysis was
performed.Results Histological inflammation was moderately severe
in the diseased bowel, while it was absent in healthy segments (P
< 0.01). TGF-[beta]1 production in healthy bowels showed a direct
correlation with clinical CD recurrence ([tau] = 0.43, P = 0.04)
and survival analysis showed that patients who expressed high TGF-[beta]1
mRNA transcripts in healthy intestines had higher cumulative recurrence
rates than those who expressed low TGF-[beta]1 mRNA levels (P = 0.02).Conclusion
Our study suggests that the high levels of TGF-[beta]1 in healthy
bowels of patients who undergo ileo-colonic resection for CD are
associated with early clinical disease recurrence, while there seems
to be no association between IGF-1 and CD recurrence.},
issn = {0022-4804},
keywords = {Crohn's disease, recurrence, TGF-[beta]1, IGF-1, myeloperoxidase},
url = {http://www.sciencedirect.com/science/article/B6WM6-4SFRDG2-3/2/eda601c1166ec83ff932b71f0c2069f5}
}
@ARTICLE{Scaruffi2010,
author = {Scaruffi, Paola and Stigliani, Sara and Coco, Simona and Valdora,
Franscesca and De Vecchi, Carla and Bonassi, Stefano and Tonini,
Gian},
title = {Transcribed-ultra conserved region expression profiling from low-input
total RNA},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {149},
number = {1},
abstract = {BACKGROUND:Ultra Conserved Regions (UCRs) are a class of 481 noncoding
sequences located in both intra- and inter-genic regions of the genome.
The recent findings that they are significantly altered in adult
chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas
lead to the hypothesis that UCRs may play a role in tumorigenesis.RESULTS:We
present a novel application of Ribo-SPIA™ isothermal linear amplification
of minute RNA quantities for quantifying Transcribed-UCR (T-UCR)
expression by quantitative PCR. Direct comparison of non-amplified
with amplified cDNA in two neuroblastoma cell lines showed that the
amplification approach increases sensitivity and repeatability in
T-UCR quantification. It is noteworthy that the Ribo-SPIA™ step allowed
us to analyze all 481 T-UCRs by using 150 ng of RNA, while introducing
a minimal bias and preserving the magnitude of relative expression.
Only the less abundant T-UCRs have high intra-assay variability,
consistently with the Poisson distribution statistics and stochastic
effects on PCR repeatability.CONCLUSIONS:We demonstrated that the
quantification procedure shown here is an accurate and reliable technique
for genome-wide non coding gene (i.e., UCRs) profiling using small
amounts of RNA. This issue is particularly important because studies
of transcription regulation are increasingly conducted in small homogeneous
samples, such as laser capture microdissected or sorted cell populations.},
doi = {10.1186/1471-2164-11-149},
issn = {1471-2164},
pubmedid = {20199688},
url = {http://www.biomedcentral.com/1471-2164/11/149}
}
@ARTICLE{Scaruffi2009,
author = {Scaruffi, Paola and Stigliani, Sara and Moretti, Stefano and Coco,
Simona and De Vecchi, Carla and Valdora, Francesca and Garaventa,
Alberto and Bonassi, Stefano and Tonini, Gian},
title = {Transcribed-ultra conserved region expression is associated with
outcome in high-risk neuroblastoma},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {441},
number = {1},
abstract = {BACKGROUND:Neuroblastoma is the most common, pediatric, extra-cranial,
malignant solid tumor. Despite multimodal therapeutic protocols,
outcome for children with a high-risk clinical phenotype remains
poor, with long-term survival still less than 40%. Hereby, we evaluated
the potential of non-coding RNA expression to predict outcome in
high-risk, stage 4 neuroblastoma.METHODS:We analyzed expression of
481 Ultra Conserved Regions (UCRs) by reverse transcription-quantitative
real-time PCR and of 723 microRNAs by microarrays in 34 high-risk,
stage 4 neuroblastoma patients.RESULTS:First, the comparison of 8
short- versus 12 long-term survivors showed that 54 UCRs were significantly
(P < 0.0491) over-expressed in the former group. For 48 Ultra Conserved
Region (UCRs) the expression levels above the cut-off values defined
by ROC curves were strongly associated with good-outcome (OS: 0.0001
31,000 gene probes represented on an Affymetrix
expression microarray, 18,976 exhibited sufficient signal for reliable
analysis and at least 2-fold variation in expression among 120 F2
rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage
analysis with 399 genetic markers revealed significant linkage with
at least one marker for 1,300 probes ({alpha} = 0.001; estimated
empirical false discovery rate = 2%). Both contiguous and noncontiguous
loci were found to be important in regulating mammalian eye gene
expression. We investigated one locus of each type in greater detail
and identified putative transcription-altering variations in both
cases. We found an inserted cREL binding sequence in the 5' flanking
sequence of the Abca4 gene associated with an increased expression
level of that gene, and we found a mutation of the gene encoding
thyroid hormone receptor [beta]2 associated with a decreased expression
level of the gene encoding short-wavelength sensitive opsin (Opn1sw).
In addition to these positional studies, we performed a pairwise
analysis of gene expression to identify genes that are regulated
in a coordinated manner and used this approach to validate two previously
undescribed genes involved in the human disease Bardet-Biedl syndrome.
These data and analytical approaches can be used to facilitate the
discovery of additional genes and regulatory elements involved in
human eye disease.},
url = {http://www.pnas.org/cgi/content/abstract/103/39/14429}
}
@ARTICLE{Scheideler2008,
author = {Scheideler, Marcel and Elabd, Christian and Zaragosi, Laure-Emmanuelle
and Chiellini, Chiara and Hackl, Hubert and Sanchez-Cabo, Fatima
and Yadav, Sunaina and Duszka, Kalina and Friedl, Gerald and Papak,
Christine and Prokesch, Andreas and Windhager, Reinhard and Ailhaud,
Gerard and Dani, Christian and Amri, Ez-Zoubir and Trajanoski, Zlatko},
title = {Comparative transcriptomics of human multipotent stem cells during
adipogenesis and osteoblastogenesis},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {340},
number = {1},
abstract = {BACKGROUND:A reciprocal relationship between bone and fat development
in osteoporosis is clinically well established. Some of the key molecular
regulators involved in this tissue replacement process have been
identified. The detailed mechanisms governing the differentiation
of mesenchymal stem cells (MSC) – the key cells involved – are however
only now beginning to emerge. In an attempt to address the regulation
of the adipocyte/osteoblast balance at the level of gene transcription
in a comprehensive and unbiased manner, we performed a large-scale
gene expression profiling study using a unique cellular model, human
multipotent adipose tissue-derived stem cells (hMADS).RESULTS:The
analysis of 1606 genes that were found to be differentially expressed
between adipogenesis and osteoblastogenesis revealed gene repression
to be most prevalent prior to commitment in both lineages. Computational
analyses suggested that this gene repression is mediated by miRNAs.
The transcriptional activation of lineage-specific molecular processes
in both cases occurred predominantly after commitment. Analyses of
the gene expression data and promoter sequences produced a set of
65 genes that are candidates for genes involved in the process of
adipocyte/osteoblast commitment. Four of these genes were studied
in more detail: LXRa and phospholipid transfer protein (PLTP) for
adipogenesis, the nuclear receptor COUP-TF1 and one uncharacterized
gene, TMEM135 for osteoblastogenesis. PLTP was secreted during both
early and late time points of hMADS adipocyte differentiation. LXRa,
COUP-TF1, and the transmembrane protein TMEM135 were studied in primary
cultures of differentiating bone marrow stromal cells from healthy
donors and were found to be transcriptionally activated in the corresponding
lineages.CONCLUSION:Our results reveal gene repression as a predominant
early mechanism before final cell commitment. We were moreover able
to identify 65 genes as candidates for genes controlling the adipocyte/osteoblast
balance and to further evaluate four of these. Additional studies
will explore the precise role of these candidate genes in regulating
the adipogenesis/osteoblastogenesis switch.},
doi = {10.1186/1471-2164-9-340},
issn = {1471-2164},
pubmedid = {18637193},
url = {http://www.biomedcentral.com/1471-2164/9/340}
}
@ARTICLE{Scheler2009,
author = {Scheler, Ott and Glynn, Barry and Parkel, Sven and Palta, Priit and
Toome, Kadri and Kaplinski, Lauris and Remm, Maido and Maher, Majella
and Kurg, Ants},
title = {Fluorescent labeling of NASBA amplified tmRNA molecules for microarray
applications},
journal = {BMC Biotechnology},
year = {2009},
volume = {9},
pages = {45},
number = {1},
abstract = {BACKGROUND:Here we present a novel promising microbial diagnostic
method that combines the sensitivity of Nucleic Acid Sequence Based
Amplification (NASBA) with the high information content of microarray
technology for the detection of bacterial tmRNA molecules. The NASBA
protocol was modified to include aminoallyl-UTP (aaUTP) molecules
that were incorporated into nascent RNA during the NASBA reaction.
Post-amplification labeling with fluorescent dye was carried out
subsequently and tmRNA hybridization signal intensities were measured
using microarray technology. Significant optimization of the labeled
NASBA protocol was required to maintain the required sensitivity
of the reactions.RESULTS:Two different aaUTP salts were evaluated
and optimum final concentrations were identified for both. The final
2 mM concentration of aaUTP Li-salt in NASBA reaction resulted in
highest microarray signals overall, being twice as high as the strongest
signals with 1 mM aaUTP Na-salt.CONCLUSION:We have successfully demonstrated
efficient combination of NASBA amplification technology with microarray
based hybridization detection. The method is applicative for many
different areas of microbial diagnostics including environmental
monitoring, bio threat detection, industrial process monitoring and
clinical microbiology.},
doi = {10.1186/1472-6750-9-45},
issn = {1472-6750},
pubmedid = {19445684},
url = {http://www.biomedcentral.com/1472-6750/9/45}
}
@ARTICLE{SCHENK2008,
author = {SCHENK, ALEXANDER and WEINGART, HELGE and ULLRICH, MATTHIAS S.},
title = {Extraction of high-quality bacterial RNA from infected leaf tissue
for bacterial in planta gene expression analysis by multiplexed fluorescent
Northern hybridization},
journal = {Molecular Plant Pathology},
year = {2008},
volume = {9},
pages = {227--235},
number = {2},
abstract = {SUMMARY Plant pathogenic bacteria possess a large number of genes
that allow them to grow and cause disease on plants. In planta gene
expression analysis is important to understand the impact of these
genes on bacterial virulence. A new mRNA-based approach using multiplexed
Northern hybridization was developed. High-quality bacterial and
plant total RNA was successfully isolated from leaf tissue infiltrated
with Pseudomonas syringae. The procedure employs a new extraction
buffer formulation containing glycine, sodium dodecylsulphate, cetyltrimethylammonium
bromide, high-molecular-weight polyethylene glycol and β-mercaptoethanol.
Cell lysis and classical acid–phenol extraction steps followed
by LiCl precipitation yielded large amounts of total RNA of high
purity and integrity. Multiplexing of DIG and chemically fluorescently
labelled RNA probes was developed and expression data were normalized
using the 23S rRNA gene as reference. The method was validated by
studying in planta expression of the P. syringae genes mucD, cmaA,
cfl, corR, corS and corP comprising a selection of highly expressed
biosynthetic and low-expressed regulatory genes. The method was assessed
regarding its sensitivity and might by useful for studying a variety
of plant–microbe interactions.},
issn = {1364-3703},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1364-3703.2007.00452.x}
}
@ARTICLE{Schenk2010,
author = {Schenk, Geert J. and Werkman, Taco and Wadman, Wytse and Veldhuisen,
Barbera and Dijkmans, Thomas F. and Blaas, Eva and Kegel, Linde and
de Kloet, E. Ron and Vreugdenhil, Erno},
title = {Over-expression of the DCLK gene transcript CARP decreases CA3/CA1
network excitability},
journal = {Brain Research},
year = {2010},
volume = {1352},
pages = {21--34},
month = sep,
abstract = {Products of the Doublecortin Like Kinase (DCLK) gene are implicated
in cortical migration and hippocampal maturation during embryogenesis.
However, one of its splice variants, called CaMK Related Peptide
(CARP), is expressed during adulthood in response to neurological
stimuli, such as kainic acid-induced seizures and BDNF-LTP. The function
of this transcript of the DCLK gene is poorly understood. To elucidate
its function during adulthood we have created transgenic mice with
over-expression of CARP in the brain. To study potential functions
of CARP in the hippocampus we performed an electrophysiological characterization
of the CA3/CA1 network of transgenic and wild-type mice and showed
that field excitatory post synaptic potentials (fEPSPs) are highly
increased in transgenic mice, while population spike amplitudes (PSAs)
remained equal between genotypes. Consequently, hippocampal CA3/CA1
network excitability was decreased in transgenic mice. In addition
we show a 2-fold up-regulation of the Ca2+-binding protein calretinin
and a down-regulation of Rapgef4, a guanine exchange factor for Rap1,
in the hippocampus. Given previously established conditions during
which CARP is induced and our current data, we propose that this
DCLK gene product affects glutamatergic neuronal transmission in
response to neurological stimuli.},
issn = {0006-8993},
keywords = {Mouse, Field potentials, qPCR, Calretinin, RapGef4},
url = {http://www.sciencedirect.com/science/article/B6SYR-50M1RXB-6/2/61bb0283e2a6106ec08c2321d11b652d}
}
@ARTICLE{Schenk2011,
author = {Schenk, Ursula and Frascoli, Michela and Proietti, Michele and Geffers,
Robert and Traggiai, Elisabetta and Buer, Jan and Ricordi, Camillo
and Westendorf, Astrid M. and Grassi, Fabio},
title = {ATP Inhibits the Generation and Function of Regulatory T Cells Through
the Activation of Purinergic P2X Receptors},
journal = {Sci. Signal.},
year = {2011},
volume = {4},
pages = {ra12--},
number = {162},
month = mar,
comment = {10.1126/scisignal.2001270},
url = {http://stke.sciencemag.org/cgi/content/abstract/sigtrans;4/162/ra12}
}
@ARTICLE{Schepeler2008,
author = {Schepeler, Troels and Reinert, Jorgen T. and Ostenfeld, Marie S.
and Christensen, Lise L. and Silahtaroglu, Asli N. and Dyrskjot,
Lars and Wiuf, Carsten and Sorensen, Frank J. and Kruhoffer, Mogens
and Laurberg, Soren and Kauppinen, Sakari and Orntoft, Torben F.
and Andersen, Claus L.},
title = {Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {6416--6424},
number = {15},
month = aug,
abstract = {MicroRNAs (miRNA) are a class of small noncoding RNAs with important
posttranscriptional regulatory functions. Recent data suggest that
miRNAs are aberrantly expressed in many human cancers and that they
may play significant roles in carcinogenesis. Here, we used microarrays
to profile the expression of 315 human miRNAs in 10 normal mucosa
samples and 49 stage II colon cancers differing with regard to microsatellite
status and recurrence of disease. Several miRNAs were differentially
expressed between normal tissue and tumor microsatellite subtypes,
with miR-145 showing the lowest expression in cancer relative to
normal tissue. Microsatellite status for the majority of cancers
could be correctly predicted based on miRNA expression profiles.
Furthermore, a biomarker based on miRNA expression profiles could
predict recurrence of disease with an overall performance accuracy
of 81%, indicating a potential role of miRNAs in determining tumor
aggressiveness. The expression levels of miR-320 and miR-498, both
included in the predictive biomarker, correlated with the probability
of recurrence-free survival by multivariate analysis. We successfully
verified the expression of selected miRNAs using real-time reverse
transcription-PCR assays for mature miRNAs, whereas in situ hybridization
was used to detect the accumulation of miR-145 and miR-320 in normal
epithelial cells and adenocarcinoma cells. Functional studies showed
that miR-145 potently suppressed growth of three different colon
carcinoma cell lines. In conclusion, our results suggest that perturbed
expression of numerous miRNAs in colon cancer may have a functional
effect on tumor cell behavior, and, furthermore, that some miRNAs
with prognostic potential could be of clinical importance. [Cancer
Res 2008;68(15):6416-24]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/15/6416}
}
@ARTICLE{Scherbik2006,
author = {Scherbik, Svetlana V. and Paranjape, Jayashree M. and Stockman, Bronislava
M. and Silverman, Robert H. and Brinton, Margo A.},
title = {RNase L Plays a Role in the Antiviral Response to West Nile Virus},
journal = {J. Virol.},
year = {2006},
volume = {80},
pages = {2987--2999},
number = {6},
month = mar,
abstract = {Alleles at the Flv locus determine disease outcome after a flavivirus
infection in mice. Although comparable numbers of congenic resistant
and susceptible mouse embryo fibroblasts (MEFs) are infected by the
flavivirus West Nile virus (WNV), resistant MEFs produce [~]100-
to 150-fold lower titers than susceptible ones and flavivirus titers
in the brains of resistant and susceptible animals can differ by
>10,000-fold. The Flv locus was previously identified as the 2'-5'
oligoadenylate synthetase 1b (Oas1b) gene. Oas gene expression is
up-regulated by interferon (IFN), and after activation by double-stranded
RNA, some mouse synthetases produce 2-5A, which activates latent
RNase L to degrade viral and cellular RNAs. To determine whether
the lower levels of intracellular flavivirus genomic RNA from resistant
mice detected in cells at all times after infection were mediated
by RNase L, RNase L activity levels in congenic resistant and susceptible
cells were compared. Similar moderate levels of RNase L activation
by transfected 2-5A were observed in both types of uninfected cells.
After WNV infection, the mRNAs of IFN-{beta} and three Oas genes
were up-regulated to similar levels in both types of cells. However,
significant levels of RNase L activity were not detected until 72
h after WNV infection and the patterns of viral RNA cleavage products
generated were similar in both types of cells. When RNase L activity
was down-regulated in resistant cells via stable expression of a
dominant negative RNase L mutant, [~]5- to 10-times-higher yields
of WNV were produced. Similarly, about [~]5- to 10-times-higher virus
yields were produced by susceptible C57BL/6 RNase L-/- cells compared
to RNase L+/+ cells that were either left untreated or pretreated
with IFN and/or poly(I) {middle dot} poly(C). The data indicate that
WNV genomic RNA is susceptible to RNase L cleavage and that RNase
L plays a role in the cellular antiviral response to flaviviruses.
The results suggest that RNase L activation is not a major component
of the Oas1b-mediated flavivirus resistance phenotype.},
url = {http://jvi.asm.org/cgi/content/abstract/80/6/2987}
}
@ARTICLE{Scherbik2007,
author = {Scherbik, Svetlana V. and Stockman, Bronislava M. and Brinton, Margo
A.},
title = {Differential Expression of Interferon (IFN) Regulatory Factors and
IFN-Stimulated Genes at Early Times after West Nile Virus Infection
of Mouse Embryo Fibroblasts},
journal = {J. Virol.},
year = {2007},
volume = {81},
pages = {12005--12018},
number = {21},
month = nov,
abstract = {Although lineage I West Nile virus (WNV) strain Eg101 induced beta
interferon (IFN-{beta}) production as early as 12 h after infection
in primary mouse embryo fibroblasts and did not inhibit the JAK-STAT
signaling pathway, it was still able to replicate efficiently. To
gain insights about possible viral countermeasures used by this virus
to suppress the host response, the cell transcriptional profile and
the kinetics of IFN regulatory factor (IRF) expression and activation
were examined at early times after infection. By 12 h after WNV infection,
the majority of the up-regulated genes were ones involved in IFN
pathways. However, comparison of IFN-stimulated gene (ISG) expression
levels in mock-infected, IFN-treated, and virus-infected cells indicated
that WNV infection suppressed the up-regulation of a subset of ISGs,
including genes involved in transcriptional regulation, apoptosis,
and stress responses, prior to 24 h after infection. Analysis of
mRNA and protein levels for representative genes indicated that suppression
was at the transcriptional and posttranscriptional levels. Translocation
of IRF-3 to the nucleus was observed beginning at 8 h, IRF-7 expression
was detected by 12 h, but IRF-1 expression was not detected until
24 h after infection. Virus-induced gene suppression was sufficient
to overcome the effect of exogenous IFN pretreatment for 1 h but
not for 4 h prior to infection. These data indicate that WNV can
selectively counteract the host response at early times after infection
by previously unreported mechanisms.},
url = {http://jvi.asm.org/cgi/content/abstract/81/21/12005}
}
@ARTICLE{Scherer2006,
author = {Scherer, Mario and Heimel, Kai and Starke, Verena and Kamper, Jorg},
title = {The Clp1 Protein Is Required for Clamp Formation and Pathogenic Development
of Ustilago maydis},
journal = {PLANT CELL},
year = {2006},
volume = {18},
pages = {2388--2401},
number = {9},
month = sep,
abstract = {In the phytopathogenic fungus Ustilago maydis, pathogenic development
is controlled by a heterodimer of the two homeodomain proteins bE
and bW, encoded by the b-mating-type locus. We have identified a
b-dependently induced gene, clampless1 (clp1), that is required for
the proliferation of dikaryotic filaments in planta. We show that
U. maydis hyphae develop structures functionally equivalent to clamp
cells that participate in the distribution of nuclei during cell
division. In clp1 mutant strains, dikaryotic filaments penetrate
the plant cuticle, but development is stalled before the first mitotic
division, and the clamp-like structures are not formed. Although
clp1 is immediately activated upon b-induction on the transcriptional
level, nuclear-localized Clp1 protein is first observed at the stage
of plant penetration prior to the first cell division. Induced expression
of clp1 strongly interferes with b-dependent gene regulation and
blocks b-dependent filament formation and b-dependent cell cycle
arrest. We speculate that the Clp1 protein inhibits the activity
of the bE/bW heterodimer to facilitate the cell cycle progression
during hyphal growth.},
url = {http://www.plantcell.org/cgi/content/abstract/18/9/2388}
}
@ARTICLE{Scherzer2007,
author = {Scherzer, Clemens R. and Eklund, Aron C. and Morse, Lee J. and Liao,
Zhixiang and Locascio, Joseph J. and Fefer, Daniel and Schwarzschild,
Michael A. and Schlossmacher, Michael G. and Hauser, Michael A. and
Vance, Jeffery M. and Sudarsky, Lewis R. and Standaert, David G.
and Growdon, John H. and Jensen, Roderick V. and Gullans, Steven
R.},
title = {Molecular markers of early Parkinson's disease based on gene expression
in blood},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {955--960},
number = {3},
month = jan,
abstract = {Parkinson's disease (PD) progresses relentlessly and affects five
million people worldwide. Laboratory tests for PD are critically
needed for developing treatments designed to slow or prevent progression
of the disease. We performed a transcriptome-wide scan in 105 individuals
to interrogate the molecular processes perturbed in cellular blood
of patients with early-stage PD. The molecular multigene marker here
identified is associated with risk of PD in 66 samples of the training
set comprising healthy and disease controls [third tertile cross-validated
odds ratio of 5.7 (P for trend 0.005)]. It is further validated in
39 independent test samples [third tertile odds ratio of 5.1 (P for
trend 0.04)]. Insights into disease-linked processes detectable in
peripheral blood are offered by 22 unique genes differentially expressed
in patients with PD versus healthy individuals. These include the
cochaperone ST13, which stabilizes heat-shock protein 70, a modifier
of {alpha}-synuclein misfolding and toxicity. ST13 messenger RNA
copies are lower in patients with PD (mean {+/-} SE 0.59 {+/-} 0.05)
than in controls (0.96 {+/-} 0.09) (P = 0.002) in two independent
populations. Thus, gene expression signals measured in blood can
facilitate the development of biomarkers for PD.},
url = {http://www.pnas.org/cgi/content/abstract/104/3/955}
}
@ARTICLE{Scherzer2008,
author = {Scherzer, Clemens R. and Grass, Jeffrey A. and Liao, Zhixiang and
Pepivani, Imelda and Zheng, Bin and Eklund, Aron C. and Ney, Paul
A. and Ng, Juliana and McGoldrick, Meghan and Mollenhauer, Brit and
Bresnick, Emery H. and Schlossmacher, Michael G.},
title = {GATA transcription factors directly regulate the Parkinson's disease-linked
gene {alpha}-synuclein},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {10907--10912},
number = {31},
month = aug,
abstract = {Increased {alpha}-synuclein gene (SNCA) dosage due to locus multiplication
causes autosomal dominant Parkinson's disease (PD). Variation in
SNCA expression may be critical in common, genetically complex PD
but the underlying regulatory mechanism is unknown. We show that
SNCA and the heme metabolism genes ALAS2, FECH, and BLVRB form a
block of tightly correlated gene expression in 113 samples of human
blood, where SNCA naturally abounds (validated P = 1.6 x 10-11, 1.8
x 10-10, and 6.6 x 10-5). Genetic complementation analysis revealed
that these four genes are co-induced by the transcription factor
GATA-1. GATA-1 specifically occupies a conserved region within SNCA
intron-1 and directly induces a 6.9-fold increase in {alpha}-synuclein.
Endogenous GATA-2 is highly expressed in substantia nigra vulnerable
to PD, occupies intron-1, and modulates SNCA expression in dopaminergic
cells. This critical link between GATA factors and SNCA may enable
therapies designed to lower {alpha}-synuclein production.},
url = {http://www.pnas.org/cgi/content/abstract/105/31/10907}
}
@ARTICLE{Scherzer2003,
author = {Scherzer, Clemens R. and Jensen, Roderick V. and Gullans, Steven
R. and Feany, Mel B.},
title = {Gene expression changes presage neurodegeneration in a Drosophila
model of Parkinson's disease},
journal = {Hum. Mol. Genet.},
year = {2003},
volume = {12},
pages = {2457--2466},
number = {19},
month = oct,
abstract = {Transgenic Drosophila expressing human {alpha}-synuclein faithfully
replicate essential features of human Parkinson's disease, including
age-dependent loss of dopaminergic neurons, Lewy-body-like inclusions
and locomotor impairment. To define the transcriptional program encoding
molecular machinery involved in {alpha}-synuclein pathology, we characterized
expression of the entire Drosophila genome at pre-symptomatic, early
and advanced disease stages. Fifty-one signature transcripts, including
lipid, energy and membrane transport mRNAs, were tightly associated
with {alpha}-synuclein expression. Most importantly, at the pre-symptomatic
stage, when the potential for neuroprotection is greatest, expression
changes revealed specific pathology. In age-matched tau transgenic
Drosophila, the transcription of {alpha}-synuclein associated genes
was normal, suggesting highly distinct pathways of neurodegeneration.
Temporal profiling of progressive gene expression changes in neurodegenerative
disease models provides unbiased starting points for defining disease
mechanisms and for identifying potential targets for neuroprotective
drugs at pre-clinical stages.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/12/19/2457}
}
@ARTICLE{Schiebold2011,
author = {Schiebold, Silke and Tschiersch, Henning and Borisjuk, Ljudmilla
and Heinzel, Nicolas and Radchuk, Ruslana and Rolletschek, Hardy},
title = {A novel procedure for the quantitative analysis of metabolites, storage
products and transcripts of laser microdissected seed tissues of
Brassica napus},
journal = {Plant Methods},
year = {2011},
volume = {7},
pages = {19},
number = {1},
abstract = {BACKGROUND:The biology of the seed is complicated by the extensive
non-homogeneity (spatial gradients) in gene expression, metabolic
conversions and storage product accumulation. The detailed understanding
of the mechanisms underlying seed growth and storage therefore requires
the development of means to obtain tissue-specific analyses. This
approach also represents an important priority in the context of
seed biotechnology.RESULTS:We provide a guideline and detailed procedures
towards the quantitative analysis of laser micro-dissected (LM) tissues
in oilseed rape (Brassica napus). This includes protocols for laser
microdissection of the seed, and the subsequent extraction and quantitative
analysis of lipids, starch and metabolites (sugars, sugar phosphates,
nucleotides, amino acids, intermediates of glycolysis and citric
acid cycle). We have also developed a protocol allowing the parallel
analysis of the transcriptome using Brassica-specific microarrays.
Some data are presented regarding the compartmentation of metabolites
within the oilseed rape embryo.CONCLUSION:The described methodology
allows for the rapid, combined analysis of metabolic intermediates,
major storage products and transcripts in a tissue-specific manner.
The protocols are robust for oilseed rape, and should be readily
adjustable for other crop species. The suite of methods applied to
LM tissues represents an important step in the context of both the
systems biology and the biotechnology of oilseeds.},
doi = {10.1186/1746-4811-7-19},
issn = {1746-4811},
pubmedid = {21718489},
url = {http://www.plantmethods.com/content/7/1/19}
}
@ARTICLE{Schiedlmeier2007,
author = {Schiedlmeier, Bernhard and Santos, Ana Cristina and Ribeiro, Ana
and Moncaut, Natalia and Lesinski, Dietrich and Auer, Herbert and
Kornacker, Karl and Ostertag, Wolfram and Baum, Christopher and Mallo,
Moises and Klump, Hannes},
title = {HOXB4's road map to stem cell expansion},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {16952--16957},
number = {43},
month = oct,
abstract = {Homeodomain-containing transcription factors are important regulators
of stem cell behavior. HOXB4 mediates expansion of adult and embryo-derived
hematopoietic stem cells (HSCs) when expressed ectopically. To define
the underlying molecular mechanisms, we performed gene expression
profiling in combination with subsequent functional analysis with
enriched adult HSCs and embryonic derivatives expressing inducible
HOXB4. Thereby, we identified a set of overlapping genes that likely
represent "universal" targets of HOXB4. A substantial number of loci
are involved in signaling pathways important for controlling self-renewal,
maintenance, and differentiation of stem cells. Functional assays
performed on selected pathways confirmed the biological coherence
of the array results. HOXB4 activity protected adult HSCs from the
detrimental effects mediated by the proinflammatory cytokine TNF-{alpha}.
This protection likely contributes to the competitive repopulation
advantage of HOXB4-expressing HSCs observed in vivo. The concept
of TNF-{alpha} inhibition may also prove beneficial for patients
undergoing bone marrow transplantation. Furthermore, we demonstrate
that HOXB4 activity and FGF signaling are intertwined. HOXB4-mediated
expansion of adult and ES cell-derived HSCs was enhanced by specific
and complete inhibition of FGF receptors. In contrast, the expanding
activity of HOXB4 on hematopoietic progenitors in day 4-6 embryoid
bodies was blunted in the presence of basic FGF (FGF2), indicating
a dominant negative effect of FGF signaling on the earliest hematopoietic
cells. In summary, our results strongly suggest that HOXB4 modulates
the response of HSCs to multiple extrinsic signals in a concerted
manner, thereby shifting the balance toward stem cell self-renewal.},
url = {http://www.pnas.org/cgi/content/abstract/104/43/16952}
}
@ARTICLE{Schielke2011,
author = {Schielke, Stephanie and Spatz, Carolin and Schwarz, Roland Felix
and Joseph, Biju and Schoen, Christoph and Schulz, Sabine Marita
and Hubert, Kerstin and Frosch, Matthias and Schubert-Unkmeir, Alexandra
and Kurzai, Oliver},
title = {Characterization of FarR as a highly specialized, growth phase-dependent
transcriptional regulator in Neisseria meningitidis},
journal = {International Journal of Medical Microbiology},
year = {2011},
volume = {301},
pages = {325--333},
number = {4},
month = apr,
abstract = {Transcriptional regulators play an important role for the survival
of Neisseria meningitidis within its human host. We have recently
shown that FarR acts as transcriptional repressor of the adhesin
nadA in N. meningitidis. Here, we examined the FarR regulon by microarray
analyses, qRT-PCR, and electrophoretic mobility shift assays, revealing
that FarR is a highly specific repressor of nadA. We demonstrate
by reporter gene fusion assays that alterations of the FarR binding
site within the nadA promoter are sufficient to induce transcription
of nadA. Furthermore, farR expression is growth phase-dependent.
The highest transcription rate was observed in the late-exponential
growth phase of meningococci. Upon contact with active components
of the complement system in normal human serum, expression of farR
is slightly downregulated. Concluding, we present FarR as an exquisitely
specialized, growth phase-dependent, possibly complement-responsive
transcriptional regulator in N. meningitidis.},
issn = {1438-4221},
keywords = {Neisseria meningitidis, FarR, Transcriptional regulation, Growth phase
dependency, Regulon},
url = {http://www.sciencedirect.com/science/article/pii/S1438422111000051}
}
@ARTICLE{Schiemann2008,
author = {Schiemann, Y. and Wegmann, M. and Lersch, P. and Heisler, E. and
Farwick, M.},
title = {Polar emollients in cosmetic formulations enhance the penetration
and biological effects of Phytosphingosine on skin},
journal = {Colloids and Surfaces A: Physicochemical and Engineering Aspects},
year = {2008},
volume = {331},
pages = {103--107},
number = {1-2},
month = dec,
abstract = {Recent cosmetic and dermatological science focuses on active ingredients
in order to support the biological function of the skin such as protection
against physical and chemical stress, UV-irradiation and microbes.
Keratinocytes represent key elements of this barrier since they form
the outer water-impermeable layers of the skin. To assure this function
keratinocytes run through a special differentiation process from
stratum basale to the stratum corneum, which is formed only of end-differentiated
keratinocytes, now called corneocytes. The other main constituent
of the water-impermeable barrier of the skin are barrier lipids i.e.
ceramides, cholesterol and free fatty acids. Ceramides are formed
by keratinocytes by amidation of sphingoid bases such as Phytosphingosine
with fatty acids. Furthermore, Phytosphingosine is a natural anti-microbial
compound and it is involved in several cellular processes such as
cell differentiation and anti-inflammation. Based on this information
the present study was aimed to evaluate the effects of Phytosphingosine
as an active ingredient in cosmetic formulations. Furthermore, here
we investigated whether the type of formulation influences the biological
activity of Phytosphingosine. For this purpose cultured keratinocytes
were incubated with Phytosphingosine and gene expression profiling
was performed using DNA micro arrays. Gene expression profiling revealed
that Phytosphingosine significantly promotes cell differentiation.
Additionally penetration studies with Phytosphingosine formulated
with cosmetic oils of different polarity were carried out using dermatomed
pig skin in Franz cells. Penetration experiments clearly showed that
the biological skin delivery of this active ingredient markedly depends
on the polarity of the utilized emollient with best penetration abilities
for polar oils. Further evaluation of the biological effects of Phytosphingosine
was accomplished by applying the different formulations on in vitro
reconstructed human epidermis with subsequent RT-qPCR analysis of
selected genes that are typical for keratinocyte differentiation.
Using this approach we were further able to demonstrate that the
biological effect of Phytosphingosine on keratinocyte differentiation
in reconstructed human epidermis is clearly dependent on the bioavailability,
which in turn is determined by the polarity of the cosmetic oil.
In conclusion, we here demonstrate that Phytosphingosine promotes
keratinocyte differentiation and, therefore, is an ideal active ingredient
for cosmetic applications whose biological activity can be enhanced
by the use of an appropriate formulation.},
booktitle = {Frontiers in Formulation Science (Formula V - 2007) - Selected papers
from the 5th international conference on Formulation Technology,
November 2007, Potsdam, Germany},
issn = {0927-7757},
keywords = {Phytosphingosine, Franz cell, Skin model, Differentiation, Penetration},
url = {http://www.sciencedirect.com/science/article/B6TFR-4T0MMFY-8/2/25b784029db43ebbf9d8d4d903abb250}
}
@ARTICLE{Schievenbusch2009,
author = {Schievenbusch, Stephanie and Strack, Ingo and Scheffler, Melanie
and Wennhold, Kerstin and Maurer, Julia and Nischt, Roswitha and
Dienes, Hans Peter and Odenthal, Margarete},
title = {Profiling of anti-fibrotic signaling by hepatocyte growth factor
in renal fibroblasts},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {385},
pages = {55--61},
number = {1},
month = jul,
abstract = {Hepatocyte growth factor (HGF) is a multifunctional growth factor
affecting cell proliferation and differentiation. Due to its mitogenic
potential, HGF plays an important role in tubular repair and regeneration
after acute renal injury. However, recent reports have shown that
HGF also acts as an anti-inflammatory and anti-fibrotic factor, affecting
various cell types such as renal fibroblasts and triggering tubulointerstitial
fibrosis of the kidney. The present study provides evidence that
HGF stimulation of renal fibroblasts results in the activation of
both the Erk1/2 and the Akt pathways. As previously shown, Erk1/2
phosphorylation results in Smad-linker phosphorylation, thereby antagonizing
cellular signals induced by TGF[beta]. By siRNA mediated silencing
of the Erk1/2-Smad linkage, however, we now demonstrate that Akt
signaling acts as an auxiliary pathway responsible for the anti-fibrotic
effects of HGF. In order to define the anti-fibrotic function of
HGF we performed comprehensive expression profiling of HGF-stimulated
renal fibroblasts by microarray hybridization. Functional cluster
analyses and quantitative PCR assays indicate that the HGF-stimulated
pathways transfer the anti-fibrotic effects in renal interstitial
fibroblasts by reducing expression of extracellular matrix proteins,
various chemokines, and members of the CCN family.},
issn = {0006-291X},
keywords = {Microarray, Smad, Akt, TGF[beta], Fibrogenesis, ECM, CCN family, CTGF,
Nov, Renal fibrosis},
url = {http://www.sciencedirect.com/science/article/B6WBK-4W7B0BR-D/2/6a460ff5371b47cb07c47b0224203edf}
}
@ARTICLE{Schilmiller2009,
author = {Schilmiller, Anthony L. and Schauvinhold, Ines and Larson, Matthew
and Xu, Richard and Charbonneau, Amanda L. and Schmidt, Adam and
Wilkerson, Curtis and Last, Robert L. and Pichersky, Eran},
title = {From the Cover: Monoterpenes in the glandular trichomes of tomato
are synthesized from a neryl diphosphate precursor rather than geranyl
diphosphate},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {10865--10870},
number = {26},
month = jun,
abstract = {We identified a cis-prenyltransferase gene, neryl diphosphate synthase
1 (NDPS1), that is expressed in cultivated tomato (Solanum lycopersicum)
cultivar M82 type VI glandular trichomes and encodes an enzyme that
catalyzes the formation of neryl diphosphate from isopentenyl diphosphate
and dimethylallyl diphosphate. mRNA for a terpene synthase gene,
phellandrene synthase 1 (PHS1), was also identified in these glands.
It encodes an enzyme that uses neryl diphosphate to produce {beta}-phellandrene
as the major product as well as a variety of other monoterpenes.
The profile of monoterpenes produced by PHS1 is identical with the
monoterpenes found in type VI glands. PHS1 and NDPS1 map to chromosome
8, and the presence of a segment of chromosome 8 derived from Solanum
pennellii LA0716 causes conversion from the M82 gland monoterpene
pattern to that characteristic of LA0716 plants. The data indicate
that, contrary to the textbook view of geranyl diphosphate as the
"universal" substrate of monoterpene synthases, in tomato glands
neryl diphosphate serves as a precursor for the synthesis of monoterpenes.},
url = {http://www.pnas.org/cgi/content/abstract/106/26/10865}
}
@ARTICLE{Schimanski2009,
author = {Schimanski, Lisa M. and Drakesmith, Hal and Sweetland, Emma and Bastin,
Judy and Rezgui, Dellel and Edelmann, Mariola and Kessler, Benedikt
and Merryweather-Clarke, Alison T. and Robson, Kathryn J.H. and Townsend,
Alain R.M.},
title = {In vitro binding of HFE to the cation-independent mannose-6 phosphate
receptor},
journal = {Blood Cells, Molecules, and Diseases},
year = {2009},
volume = {43},
pages = {180--193},
number = {2},
month = sep,
abstract = {Hereditary hemochromatosis is most frequently associated with mutations
in HFE, which encodes a class Ib histocompatibility protein. HFE
binds to the transferrin receptor-1 (TfR1) in competition with iron-loaded
transferrin (Fe-Tf). HFE is released from TfR1 by increasing concentrations
of Fe-Tf, and free HFE may then regulate iron homeostasis by binding
other ligands. To search for new HFE ligands we expressed recombinant
forms of HFE in the human cell line 293T. HFE protein was purified,
biotinylated and made into fluorescently labelled tetramers. HFE
tetramers bound to TfR1 in competition with Tf, but in addition we
detected a binding activity on some cell types that was not blocked
by Fe-Tf or by mutations in HFE that prevent binding to TfR1. We
identified this second HFE ligand as the cation independent mannose-6-phosphate
receptor (CI-MPR, also known as the insulin-like growth factor-2
receptor, IGF2R). HFE:CI-MPR binding was mediated through phosphorylated
mannose residues on HFE. Recombinant murine Hfe also bound to CI-MPR.
HFE bound to TfR1 was prevented from binding CI-MPR until released
by increasing concentrations of Fe-Tf, a feature consistent with
an iron sensing mechanism. However, it remains to be determined whether
endogenous HFE in vivo also acquires the mannose-6 phosphate modification
and binds to CI-MPR.},
issn = {1079-9796},
keywords = {HFE, Tetramer, Transferrin receptor, Cation independent mannose-6-phosphate
receptor, Mannose-6 phosphate},
url = {http://www.sciencedirect.com/science/article/B6WBV-4WDNBYF-1/2/c4c9cfbecb6d90a089f6fa0348d313b7}
}
@ARTICLE{Schimmelpfeng2004,
author = {Schimmelpfeng, J. and Weibezahn, K. F. and Dertinger, H.},
title = {Quantification of NGF-dependent neuronal differentiation of PC-12
cells by means of neurofilament-L mRNA expression and neuronal outgrowth},
journal = {Journal of Neuroscience Methods},
year = {2004},
volume = {139},
pages = {299--306},
number = {2},
month = oct,
abstract = {We demonstrate that the degree of neuronal development of PC-12 cell
differentiation can be quantified by the expression of neurofilament-L
(NF-L) mRNA, when an optimal concentration of NGF (50 ng/ml) is used.
During the first 7 days of NGF treatment, the relative amount of
NF-L mRNA was found to increase continuously and to correlate with
the outgrowth of neurites in a statistically significant way. Thus,
mRNA expression is, under these conditions, a suitable means for
reliably monitoring the differentiation of PC-12 cells as early as
after 3 days of NGF treatment. The results obtained with 5 ng/ml
NGF differ from those with 50 ng/ml: during the first 3 days of NGF
treatment, neuronal outgrowth was less than with 50 ng/ml, although
the NF-L mRNA levels did not depend significantly on NGF concentration.
Beyond day 3, NF-L mRNA levels did not increase further at 5 ng/ml
as opposed to 50 ng/ml NGF. These differences point to different
signal transduction processes involved in neuronal differentiation
at high and low NGF concentration. Expression of NF-L protein in
response to NGF treatment was also demonstrated. In summary, our
results stress that stable and sustained differentiation of PC-12
cells can only be achieved with 50 ng/ml NGF.},
issn = {0165-0270},
keywords = {Neuritogenesis, Neurite formation, Gene expression, Dose-response
relations, Pearson's correlation, Quantitative assay for neuronal
differentiation},
url = {http://www.sciencedirect.com/science/article/B6T04-4CS4RY0-1/2/01cd180a71535f64846e7c8af377ad8b}
}
@ARTICLE{Schindler2005,
author = {Schindler, Heike and Wiese, Anja and Auer, Johannes and Burtscher,
Helmut},
title = {cRNA target preparation for microarrays: Comparison of gene expression
profiles generated with different amplification procedures},
journal = {Analytical Biochemistry},
year = {2005},
volume = {344},
pages = {92--101},
number = {1},
month = sep,
abstract = {Microarray technology has become a standard tool for generation of
gene expression profiles to explore human disease processes. Being
able to start from minute amounts of RNA extends the fields of application
to core needle biopsies, laser capture microdissected cells, and
flow-sorted cells. Several RNA amplification methods have been developed,
but no extensive comparability and concordance studies of gene expression
profiles are available. Different amplification methods may produce
differences in gene expression patterns. Therefore, we compared profiles
processed by a standard microarray protocol with three different
types of RNA amplification: (i) two rounds of linear target amplification,
(ii) random amplification, and (iii) amplification based on a template
switching mechanism. The latter two methods accomplish target amplification
in a nonlinear way using PCR technology. Starting from as little
as 50 ng of total RNA, the yield of labeled cRNA was sufficient for
hybridization to Affymetrix HG-U133A GeneChip array using the respective
methods. Replicate experiments were highly reproducible for each
method. In comparison with the standard protocol, all three approaches
are less sensitive and introduced a minor but clearly detectable
bias of the detection call. In conclusion, the three amplification
protocols used are applicable for GeneChip analysis of small tissue
samples.},
issn = {0003-2697},
keywords = {Gene expression, Microarray, RNA amplification},
url = {http://www.sciencedirect.com/science/article/B6W9V-4GFV2BR-1/2/f30bfe5c7ab99f1780a42cff240bb2d7}
}
@ARTICLE{Schinwald2011,
author = {Schinwald, Anja and Murphy, Fiona A. and Jones, Alan and MacNee,
William and Donaldson, Ken},
title = {Graphene-Based Nanoplatelets: A New Risk to the Respiratory System
as a Consequence of Their Unusual Aerodynamic Properties},
journal = {ACS Nano},
year = {2011},
volume = {0},
pages = {null},
number = {0},
abstract = { Graphene is a new nanomaterial with unusual and useful physical and
chemical properties. However, in the form of nanoplatelets this new,
emerging material could pose unusual risks to the respiratory system
after inhalation exposure. The graphene-based nanoplatelets used
in this study are commercially available and consist of several sheets
of graphene (few-layer graphene). We first derived the respirability
of graphene nanoplatelets (GP) from the basic principles of the aerodynamic
behavior of plate-shaped particles which allowed us to calculate
their aerodynamic diameter. This showed that the nanoplatelets, which
were up to 25 μm in diameter, were respirable and so would deposit
beyond the ciliated airways following inhalation. We therefore utilized
models of pharyngeal aspiration and direct intrapleural installation
of GP, as well as an in vitro model, to assess their inflammatory
potential. These large but respirable GP were inflammogenic in both
the lung and the pleural space. MIP-1α, MCP-1, MIP-2, IL-8, and
IL-1β expression in the BAL, the pleural lavage, and cell culture
supernatant from THP-1 macrophages were increased with GP exposure
compared to controls but not with nanoparticulate carbon black (CB).
In vitro, macrophages exposed to GP showed expression of IL-1β.
This study highlights the importance of nanoplatelet form as a driver
for in vivo and in vitro inflammogenicity by virtue of their respirable
aerodynamic diameter, despite a considerable 2-dimensional size which
leads to frustrated phagocytosis when they deposit in the distal
lungs and macrophages attempt to phagocytose them. Our data suggest
that nanoplatelets pose a novel nanohazard and structure-toxicity
relationship in nanoparticle toxicology. },
doi = {10.1021/nn204229f},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/nn204229f},
url = {http://pubs.acs.org/doi/abs/10.1021/nn204229f}
}
@ARTICLE{Schirmer2009,
author = {Schirmer, Stephan H. and Fledderus, Joost O. and van der Laan, Anja
M. and van der Pouw-Kraan, Tineke C.T.M. and Moerland, Perry D. and
Volger, Oscar L. and Baggen, Josefien M. and Böhm, Michael and Piek,
Jan J. and Horrevoets, Anton J.G. and van Royen, Niels},
title = {Suppression of inflammatory signaling in monocytes from patients
with coronary artery disease},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2009},
volume = {46},
pages = {177--185},
number = {2},
month = feb,
abstract = {Monocytes and T-cells play an important role in the development of
atherosclerotic coronary artery disease (CAD). Transcriptome analysis
of circulating mononuclear cells from carefully matched atherosclerotic
and control patients will potentially provide insights into the pathophysiology
of atherosclerosis and supply biomarkers for diagnostic purposes.
From patients undergoing coronary angiography because of anginal
symptoms, we carefully matched 18 patients with severe triple-vessel
CAD to 13 control patients without angiographic signs of CAD. All
patients were on statin and aspirin treatment. Elevated soluble-ICAM
levels demonstrated increased vascular inflammation in atherosclerotic
patients. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated
monocytes, and macrophages was subjected to genome-wide expression
analysis. In CD14+ monocytes, few inflammatory genes were overexpressed
in control patients, while atherosclerotic patients showed overexpression
of a group of Krüppel-associated box - containing transcription factors
involved in negative regulation of gene expression. These differences
disappeared upon LPS-stimulation or differentiation towards macrophages.
No consistent changes in T cell transcriptomes were detected. Large
inter-individual variability prevented the use of single differentially
expressed genes as biomarkers, while monocyte gene expression signature
predicted patient status with an accuracy of 84%. In this comprehensive
analysis of circulating cell transcriptomes in atherosclerotic CAD,
cautious patient matching revealed only small differences in transcriptional
activity in different mononuclear cell types. Only an indication
of a negative feedback to inflammatory gene expression was detected
in atherosclerotic patients. Transcriptome differences of circulating
cells possibly play less of a role than hitherto thought in the individual
patient's susceptibility to atherosclerotic CAD, when appropriately
matched for clinical symptoms and medication taken.},
issn = {0022-2828},
keywords = {Atherosclerosis, Monocytes, Gene expression, Inflammation, Activation,
Vascular biology},
url = {http://www.sciencedirect.com/science/article/B6WK6-4TXF861-2/2/55ec15d77bb2a07d36fa6b3a93a803db}
}
@ARTICLE{Schirra2006,
author = {Schirra, Frank and Richards, Stephen M. and Liu, Meng and Suzuki,
Tomo and Yamagami, H. and Sullivan, David A.},
title = {Androgen regulation of lipogenic pathways in the mouse meibomian
gland},
journal = {Experimental Eye Research},
year = {2006},
volume = {83},
pages = {291--296},
number = {2},
month = aug,
abstract = {We hypothesize that androgens regulate lipogenesis in the meibomian
gland. To test this hypothesis, we sought to determine whether androgens
increase the mRNA levels of key lipogenic enzymes involved in the
synthesis of cholesterol and fatty acids. In addition, we examined
whether androgens stimulate the expression of genes for sterol regulatory
element binding proteins (SREBP) 1 and 2, which are transcription
factors that play an important role in the coordinate regulation
of lipogenic enzymes. Meibomian glands were obtained from castrated
mice, that were treated with vehicle or testosterone for 2 weeks.
Tissues were processed for the analysis of selected mRNAs by real-time
PCR. Our results show that testosterone increases the mRNA levels
of critical lipogenic enzymes, including those related to ATP-citrate
lyase, acetyl-CoA-synthase, acetyl-CoA-carboxylase, acetoacetyl-CoA-synthase
and 3-hydroxy-3-methylglutaryl CoA synthase 1. Our findings also
demonstrate that androgens upregulate the expression of genes encoding
the transcription factors SREBPs 1 and 2. Our results indicate that
androgens may control multiple aspects of lipogenesis in the meibomian
gland.},
issn = {0014-4835},
keywords = {meibomian gland, androgen, lipogenesis, gene expression, SREBP, tear
film, dry eye, real-time PCR, mouse},
url = {http://www.sciencedirect.com/science/article/B6WFD-4JKYWGN-1/2/4b5f6d9beff51abf8a9440169ed13891}
}
@ARTICLE{Schirra2005,
author = {Schirra, Frank and Suzuki, Tomo and Richards, Stephen M. and Jensen,
Roderick V. and Liu, Meng and Lombardi, Michael J. and Rowley, Patricia
and Treister, Nathaniel S. and Sullivan, David A.},
title = {Androgen Control of Gene Expression in the Mouse Meibomian Gland},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2005},
volume = {46},
pages = {3666--3675},
number = {10},
month = oct,
abstract = {PURPOSE. In prior work, it has been found that the meibomian gland
is an androgen target organ, that androgens modulate lipid production
within this tissue, and that androgen deficiency is associated with
glandular dysfunction and evaporative dry eye. This study's purpose
was to test the hypothesis that the androgen control of the meibomian
gland involves the regulation of gene expression. METHODS. Meibomian
glands were obtained from orchiectomized mice that were treated with
placebo or testosterone for 14 days. Tissues were processed for the
analysis of differentially expressed mRNAs by using gene bioarrays,
gene chips, and real-time PCR procedures. Bioarray data were analyzed
with GeneSifter software (VizX Labs LLC, Seattle, WA). RESULTS. The
results show that testosterone influenced the expression of more
than 1590 genes in the mouse meibomian gland. This hormone action
involved a significant upregulation of 1080 genes (e.g., neuromedin
B), and a significant downregulation of 518 genes (e.g., small proline-rich
protein 2A). Some of the most significant androgen effects were directed
toward stimulation of genes associated with lipid metabolism, sterol
biosynthesis, fatty acid metabolism, protein transport, oxidoreductase
activity, and peroxisomes. CONCLUSIONS. These findings demonstrate
that testosterone regulates the expression of numerous genes in the
mouse meibomian gland and that many of these genes are involved in
lipid metabolic pathways.},
url = {http://www.iovs.org/cgi/content/abstract/46/10/3666}
}
@ARTICLE{Schjoldager2008,
author = {Schjoldager, Katrine T.-B. G. and Maltesen, Henrik R. and Balmer,
Sophie and Lund, Leif R. and Claesson, Mogens H. and Sjostrom, Hans
and Troelsen, Jesper T. and Olsen, Jorgen},
title = {Cellular cross talk in the small intestinal mucosa: postnatal lymphocytic
immigration elicits a specific epithelial transcriptional response},
journal = {Am J Physiol Gastrointest Liver Physiol},
year = {2008},
volume = {294},
pages = {G1335--1343},
number = {6},
month = jun,
abstract = {During the early postnatal period lymphocytes migrate into the mouse
small intestine. Migrating infiltrative lymphocytes have the potential
to affect the epithelial cells via secreted cytokines. Such cross
talk can result in the elicitation of an epithelial transcriptional
response. Knowledge about such physiological cross talk between the
immune system and the epithelium in the postnatal small intestinal
mucosa is lacking. We have investigated the transcriptome changes
occurring in the postnatal mouse small intestine using DNA microarray
technology, immunocytochemistry, and quantitative real-time RT-PCR
analysis. The DNA microarray data were analyzed bioinformatically
by using a combination of projections to latent structures analysis
and functional annotation analysis. The results show that infiltrating
lymphocytes appear in the mouse small intestine in the late postweaning
period and give rise to distinct changes in the epithelial transcriptome.
Of particular interest is the expression of three genes encoding
a mucin (Muc4), a mucinlike protein (16000D21Rik), and ATP citrate
lyase (Acly). All three genes were shown to be expressed by the epithelium
and to be upregulated in response to lymphocytic migration into the
small intestinal mucosa.},
url = {http://ajpgi.physiology.org/cgi/content/abstract/294/6/G1335}
}
@ARTICLE{Schlaeger2008,
author = {Schlaeger, Christof and Longerich, Thomas and Schiller, Claudia and
Bewerunge, Peter and Mehrabi, Arianeb and Toedt, Grischa and Kleeff,
Jörg and Ehemann, Volker and Eils, Roland and Lichter, Peter and
Schirmacher, Peter and Radlwimmer, Bernhard},
title = {Etiology-dependent molecular mechanisms in human hepatocarcinogenesis},
journal = {Hepatology},
year = {2008},
volume = {47},
pages = {511--520},
number = {2},
abstract = {Abstract 10.1002/hep.22033.abs Hepatocellular carcinoma (HCC) is one
of the most common cancers worldwide and is characterized by aggressive
tumor behavior coupled with poor prognosis. Various etiologies have
been linked to HCC development, most prominently chronic hepatitis
B and C virus infections as well as chronic alcohol consumption.
In approximately 10% of HCCs, the etiology remains cryptic; however,
recent epidemiological data suggest that most of these cryptogenic
HCCs develop due to nonalcoholic steatohepatitis. To identify etiology-dependent
DNA copy number aberrations and genes relevant to hepatocarcinogenesis,
we performed array-based comparative genomic hybridization of 63
HCCs of well-defined etiology and 4 HCC cell lines followed by gene
expression profiling and functional analyses of candidate genes.
For a 10-megabase chromosome region on 8q24, we observed etiology-dependent
copy number gains and MYC overexpression in viral and alcohol-related
HCCs, resulting in up-regulation of MYC target genes. Cryptogenic
HCCs showed neither 8q24 gains, nor MYC overexpression, nor target
gene activation, suggesting that tumors of this etiology develop
by way of a distinct MYC-independent pathomechanism. Furthermore,
we detected several etiology-independent small chromosome aberrations,
including amplification of MDM4 on 1q32.1 and frequent gains of EEF1A2
on 20q13.33. Both genes were overexpressed in approximately half
the HCCs examined, and gene silencing reduced cell viability as well
as proliferation and increased apoptosis rates in HCC cell lines.
Conclusion: Our findings suggest that MDM4 and EEF1A2 act as etiology-independent
oncogenes in a significant percentage of HCCs. (HEPATOLOGY 2008.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.22033}
}
@ARTICLE{Schlecht2004,
author = {Schlecht, Ulrich and Demougin, Philippe and Koch, Reinhold and Hermida,
Leandro and Wiederkehr, Christa and Descombes, Patrick and Pineau,
Charles and Jegou, Bernard and Primig, Michael},
title = {Expression Profiling of Mammalian Male Meiosis and Gametogenesis
Identifies Novel Candidate Genes for Roles in the Regulation of Fertility},
journal = {Mol. Biol. Cell},
year = {2004},
volume = {15},
pages = {1031--1043},
number = {3},
month = mar,
abstract = {We report a comprehensive large-scale expression profiling analysis
of mammalian male germ cells undergoing mitotic growth, meiosis,
and gametogenesis by using high-density oligonucleotide microarrays
and highly enriched cell populations. Among 11,955 rat loci investigated,
1268 were identified as differentially transcribed in germ cells
at subsequent developmental stages compared with total testis, somatic
Sertoli cells as well as brain and skeletal muscle controls. The
loci were organized into four expression clusters that correspond
to somatic, mitotic, meiotic, and postmeiotic cell types. This work
provides information about expression patterns of [~]200 genes known
to be important during male germ cell development. Approximately
40 of those are included in a group of 121 transcripts for which
we report germ cell expression and lack of transcription in three
somatic control cell types. Moreover, we demonstrate the testicular
expression and transcriptional induction in mitotic, meiotic, and/or
postmeiotic germ cells of 293 as yet uncharacterized transcripts,
some of which are likely to encode factors involved in spermatogenesis
and fertility. This group also contains potential germ cell-specific
targets for innovative contraceptives. A graphical display of the
data is conveniently accessible through the GermOnline database at
http://www.germonline.org.},
url = {http://www.molbiolcell.org/cgi/content/abstract/15/3/1031}
}
@ARTICLE{Schlecht2008,
author = {Schlecht, Ulrich and Erb, Ionas and Demougin, Philippe and Robine,
Nicolas and Borde, Valerie and Nimwegen, Erik van and Nicolas, Alain
and Primig, Michael},
title = {Genome-wide Expression Profiling, In Vivo DNA Binding Analysis, and
Probabilistic Motif Prediction Reveal Novel Abf1 Target Genes during
Fermentation, Respiration, and Sporulation in Yeast},
journal = {Mol. Biol. Cell},
year = {2008},
volume = {19},
pages = {2193--2207},
number = {5},
month = may,
abstract = {The autonomously replicating sequence binding factor 1 (Abf1) was
initially identified as an essential DNA replication factor and later
shown to be a component of the regulatory network controlling mitotic
and meiotic cell cycle progression in budding yeast. The protein
is thought to exert its functions via specific interaction with its
target site as part of distinct protein complexes, but its roles
during mitotic growth and meiotic development are only partially
understood. Here, we report a comprehensive approach aiming at the
identification of direct Abf1-target genes expressed during fermentation,
respiration, and sporulation. Computational prediction of the protein's
target sites was integrated with a genome-wide DNA binding assay
in growing and sporulating cells. The resulting data were combined
with the output of expression profiling studies using wild-type versus
temperature-sensitive alleles. This work identified 434 protein-coding
loci as being transcriptionally dependent on Abf1. More than 60%
of their putative promoter regions contained a computationally predicted
Abf1 binding site and/or were bound by Abf1 in vivo, identifying
them as direct targets. The present study revealed numerous loci
previously unknown to be under Abf1 control, and it yielded evidence
for the protein's variable DNA binding pattern during mitotic growth
and meiotic development.},
url = {http://www.molbiolcell.org/cgi/content/abstract/19/5/2193}
}
@ARTICLE{Schliebe2008,
author = {Schliebe, Nicole and Strotmann, Rainer and Busse, Kathy and Mitschke,
Doreen and Biebermann, Heike and Schomburg, Lutz and Kohrle, Josef
and Bar, Jorg and Rompler, Holger and Wess, Jurgen and Schoneberg,
Torsten and Sangkuhl, Katrin},
title = {V2 vasopressin receptor deficiency causes changes in expression and
function of renal and hypothalamic components involved in electrolyte
and water homeostasis},
journal = {Am J Physiol Renal Physiol},
year = {2008},
volume = {295},
pages = {F1177--1190},
number = {4},
month = oct,
abstract = {Polyuria, hypernatremia, and hypovolemia are the major clinical signs
of inherited nephrogenic diabetes insipidus (NDI). Hypernatremia
is commonly considered a secondary sign caused by the net loss of
water due to insufficient insertion of aquaporin-2 water channels
into the apical membrane of the collecting duct cells. In the present
study, we employed transcriptome-wide expression analysis to study
gene expression in V2 vasopressin receptor (Avpr2)-deficient mice,
an animal model for X-linked NDI. Gene expression changes in NDI
mice indicate increased proximal tubular sodium reabsorption. Expression
of several key genes including Na+-K+-ATPase and carbonic anhydrases
was increased at the mRNA levels and accompanied by enhanced enzyme
activities. In addition, altered expression was also observed for
components of the eicosanoid and thyroid hormone pathways, including
cyclooxygenases and deiodinases, in both kidney and hypothalamus.
These effects are likely to contribute to the clinical NDI phenotype.
Finally, our data highlight the involvement of the renin-angiotensin-aldosterone
system in NDI pathophysiology and provide clues to explain the effectiveness
of diuretics and indomethacin in the treatment of NDI.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/295/4/F1177}
}
@ARTICLE{Schliephake2012,
author = {Henning Schliephake and Christian Bötel and Anne Förster and Bernd
Schwenzer and Judith Reichert and Dieter Scharnweber},
title = {Effect of oligonucleotide mediated immobilization of bone morphogenic
proteins on titanium surfaces},
journal = {Biomaterials},
year = {2012},
volume = {33},
pages = {1315 - 1322},
number = {5},
abstract = {The aim of the present study was to test the hypothesis that oligonucleotides
can be used for anchorage and slow release of osteogenic growth factors
such as BMP to enhance the osteogenic activity of a titanium implant
surface. Strands of 60-mer non-coding DNA oligonucleotides (ODN)
were bound to an acid-etched sandblasted cp Ti-surface by nanomechanical
fixation using anodic polarization. RhBMP2 that had been conjugated
to complementary strands of DNA oligonucleotides was then bound to
the anchored ODN strands by hybridization. Binding studies showed
a higher binding capacity compared to non-conjugated BMP2. Long term
release experiments demonstrated a continuous release from all surfaces
that was lowest for the conjugated BMP2 bound to the ODN anchor strands.
Proliferation of human bone marrow stroma cells (hBMSC) was significantly
increased on these surfaces. Immunofluorescence showed that hBMSC
grown on surfaces coated with specifically bound conjugated BMP2
developed significantly higher numbers of focal adhesion points and
exhibited significantly higher levels of transcription of osteogenic
markers alkaline phosphatase and osteopontin at early intervals.
Biological activity (induction of alkaline phosphatase) of conjugated
BMP2 released from the surface was comparable to released non-conjugated
BMP2, indicating that conjugation did not negatively affect the activity
of the released molecules. In conclusion the present study has shown
that BMP2 conjugated to ODN strands and hybridized to complementary
ODN strands anchored to a titanium surface has led to slow growth
factor release and can enhance the osteogenic activity of the titanium
surface.},
doi = {10.1016/j.biomaterials.2011.10.027},
issn = {0142-9612},
keywords = {Bone morphogenic proteins},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211012300}
}
@ARTICLE{Schling2006,
author = {Schling, Petra and Rudolph, Christian and Heimerl, Susanne and Fruth,
Sabine and Schmitz, Gerd},
title = {Expression of tumor necrosis factor alpha and its receptors during
cellular differentiation},
journal = {Cytokine},
year = {2006},
volume = {33},
pages = {239--245},
number = {5},
month = mar,
abstract = {Tumor necrosis factor alpha (TNF[alpha]) is a potent proinflammatory
cytokine also involved in cellular differentiation processes. TNF[alpha]
and both of its receptors (TNFR1 and TNFR2) can be co-expressed on
the same cell, allowing for local signaling. This study has examined
the expression of all components necessary for autocrine cytokine
regulation during human hematopoietic, epithelial, and mesenchymal
models of cellular differentiation. Macrophage and dendritic differentiation
of human peripheral blood monocytes decreased their TNF[alpha] and
TNFR2 expression while increasing the TNFR1 mRNA. In colon epithelial
cell lines (HT-29 and Caco-2) TNF[alpha]-, TNFR1-, and TNFR2-expression
was decreased upon differentiation. No changes, however, were seen
during human skin keratinocyte differentiation. TNFR1 expression
was unchanged in all three mesenchymal lineages (adipogenesis, chondrogenesis,
osteogenesis) tested. Differentiation decreases the TNF[alpha] message
in adipocytes and the TNFR2 mRNA in adipocytes and osteocytes. Our
results demonstrate that there is no general principle for TNF[alpha]
signaling during conversion of cells from progenitor to a more differentiated
phenotype. Paracrine signaling by TNF[alpha] to orchestrate different
cell types during tissue development and remodeling, therefore, probably
overrides the autocrine regulation of differentiation by TNF[alpha].
Non-signaling TNF-receptors may protect chondrocytes and osteocytes
from the anti-differentiation effects of local TNF[alpha] production.},
issn = {1043-4666},
keywords = {Adipocyte, Chondrocyte, Epithelial cell, Osteocyte, Peripheral blood
monocyte},
url = {http://www.sciencedirect.com/science/article/B6WDF-4JKYTNB-2/2/2a5527517ac15654b3871fe06eeb0329}
}
@ARTICLE{Schlingemann2005,
author = {Schlingemann, Joerg and Thuerigen, Olaf and Ittrich, Carina and Toedt,
Grischa and Kramer, Heidi and Hahn, Meinhard and Lichter, Peter},
title = {Effective transcriptome amplification for expression profiling on
sense-oriented oligonucleotide microarrays},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {e29--},
number = {3},
month = feb,
abstract = {Gene expression analysis using microarrays of synthetic long oligonucleotides
is limited in that it requires substantial amounts of RNA. To obtain
these quantities from minute amounts of starting material, protocols
were developed that linearly amplify mRNA by cDNA synthesis and in
vitro transcription. Since orientation of the product is antisense
(aRNA), it is inapplicable for dye-labelling by reverse transcription
and hybridization to sense-oriented oligonucleotide arrays. Here,
we introduce a novel protocol in which aRNA labelling is achieved
by a combination of two reverse and one forward transcription reactions
followed by dye-incorporation using Klenow fragment, generating fluorescent
antisense cDNA. We demonstrate high fidelity in arrays using up to
105-fold amplification, starting from 2 ng total RNA. The generated
data are highly reproducible and maintain relative gene expression
levels between samples. These results demonstrate that our protocol
describes an efficient and reliable technique to expand the applicability
of oligonucleotide arrays to studies where RNA is the limited source
material.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/3/e29}
}
@ARTICLE{Schlink2011,
author = {Schlink, K.},
title = {Gene expression profiling in wounded and systemic leaves of Fagus
sylvatica reveals up-regulation of ethylene and jasmonic acid signalling},
journal = {Plant Biology},
year = {2011},
volume = {13},
pages = {445--452},
number = {3},
abstract = {Abstract Wounding is a crucial threat to plants because of the physical
damage caused and the possible entry of pathogens. Little is known
about the wound reaction in forest trees. Therefore, leaves of young
beech trees were wounded and the transcriptional response of wounded
leaves and leaves directly above and below was analysed. A total
of 123 genes exhibited significant regulation. The magnitude of regulation
was slightly weaker in the downward leaves but the regulation pattern
resembles that of the local and upward reactions. Thus, the signal
was transduced in both vertical directions. Genes exhibiting major
regulation lacked functional assignment or belonged to signalling,
transcription and defence categories. Signalling included activation
of transcripts in the calcium and ethylene pathways. There was also
evidence for activation of jasmonic acid signalling, but no activation
of jasmonic acid-responsive PR (pathogenesis-related) genes was observed.
Moreover, repression of salicylic acid responsive defence was measured.
Metabolic changes included induction of a core gene of the phenylpropanoid
pathway, while energy metabolism exhibited down-regulation. These
results support the conclusion that young beech trees might give
up leaves and/or reduce leaf energy content after an attack so as
to deprive a putative herbivore of a nutrient supply, instead of
investing much energy in leaf defence.},
doi = {10.1111/j.1438-8677.2010.00397.x},
issn = {1438-8677},
keywords = {European beech, repression of salicylic acid defence and energy metabolism,
vertical signal transduction},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1438-8677.2010.00397.x}
}
@ARTICLE{Schlipf2011,
author = {Schlipf, NA and Schüle, R and Klimpe, S and Karle, KN and Synofzik,
M and Schicks, J and Riess, O and Schöls, L and Bauer, P},
title = {Amplicon-based high-throughput pooled sequencing identifies mutations
in CYP7B1 and SPG7 in sporadic spastic paraplegia patients},
journal = {Clinical Genetics},
year = {2011},
volume = {80},
pages = {148--160},
number = {2},
abstract = {Schlipf NA, Schüle R, Klimpe S, Karle KN, Synofzik M, Schicks J,
Riess O, Schöls L, Bauer P. Amplicon-based high-throughput pooled
sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic
paraplegia patients.Hereditary spastic paraplegia (HSP) is a neurodegenerative
disorder defined clinically by progressive lower limb spasticity
and weakness. HSP is a genetically highly heterogeneous condition
with at least 46 gene loci identified so far, involving X-linked,
autosomal recessive (AR) and autosomal dominant inheritance. For
correct diagnosis, molecular testing is essential because clinical
parameters by themselves are not reliable to differentiate HSP forms.
The purpose of this study was to establish amplicon-based high-throughput
genotyping for AR-HSP. A sample of 187 index cases with apparently
sporadic or recessive spastic paraplegia were analyzed by applying
an array-based amplification strategy. Amplicon libraries of the
CYP7B1–(SPG5) and SPG7–gene were generated followed by a pooled
next-generation sequencing (NGS) approach. We identified three SPG5
and seven SPG7 patients. All had one homozygous or two heterozygous
mutations. In total, 20 distinct mutations (CYP7B1,n = 4and SPG7,n
= 16) including two novel CYP7B1 mutations (p.G51R and p.E211KfsX3)
and eight novel SPG7 mutations (p.Leu8delinsLeuLeu, p.W29X, p.R139X,
p.R247X, p.G344D, p.Leu346_Leu347ins11, p.R398X and p.R398Q) were
detected by this comprehensive genetic testing. Our study illustrates
how amplicon-based NGS can be used as an efficient tool to study
genotypes and mutations in large patient cohorts and complex phenotypes.},
doi = {10.1111/j.1399-0004.2011.01715.x},
issn = {1399-0004},
keywords = {amplicon-based next-generation sequencing, CYP7B1, hereditary spastic
paraplegia, paraplegin, SPG5, SPG7},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-0004.2011.01715.x}
}
@ARTICLE{Schlomm2009,
author = {Schlomm, Thorsten and Hellwinkel, Olaf J.C. and Buness, Andreas and
Ruschhaupt, Markus and Lübke, Andreas M. and Chun, Felix K. and Simon,
Ronald and Budäus, Lars and Erbersdobler, Andreas and Graefen, Markus
and Huland, Hartwig and Poustka, Annemarie and Sültmann, Holger},
title = {Molecular Cancer Phenotype in Normal Prostate Tissue},
journal = {European Urology},
year = {2009},
volume = {55},
pages = {885--891},
number = {4},
month = apr,
abstract = {Background Insufficient sensitivity and specificity of prostate biopsies
for cancer detection.Objectives Based on evidence from our microarray
analyses, we hypothesized that considerable molecular changes precede
morphologically detectable malignant transformation of prostate epithelial
tissues. The identification of such changes could lead to novel strategies
in the clinical management of prostate cancer.Design, Setting, and
Participants Histologically normal, fresh prostate tissue from prostate
cancer patients, healthy donors, and cancer suspect patients with
continuous negative biopsies were analyzed.Measurements To identify
molecular changes between 29 tumor-free prostate tissues from healthy
donors and 27 patients with proven prostate cancer, we performed
a global microarray screening. Based on this screening as well as
literature data, we selected a subset of 29 genes for validation
by arrayed real-time reverse transcription-polymerase chain reaction
(RT-PCR) using histologically tumor-free biopsy samples from 114
patients representing three prostate cancer risk groups.Results and
Limitations We identified five genes (FOS, EGR1, MYC, TFRC, and FOLH1),
which displayed significant differential expression between morphologically
normal prostate tissues from men of each of the three risk groups.
These results were independent from age, prostate-specific antigen
(PSA), frequency and timing of previous prostate biopsies, tissue
composition, tumor stage, and tumor grade. In univariate logistic
regression analyses, the transcript levels of these genes were found
to be highly indicative for the presence or absence of cancer in
the entire prostate. The study was designed as a proof of principle.
The clinical relevance of our results has to be evaluated in a larger
clinical setting.Conclusions Our results suggest a measurable molecular
cancer phenotype in histologically normal prostate tissue indicating
the presence of prostate cancer elsewhere in the organ.},
issn = {0302-2838},
keywords = {Prostate Cancer, RNA, Gene expression, Gene, Normal tissue},
url = {http://www.sciencedirect.com/science/article/B6X10-4SHN8RK-1/2/55cc6adbc998f6bee0bea12c6f3f1b8c}
}
@ARTICLE{Schlomm2008,
author = {Schlomm, Thorsten and Näkel, Esther and Lübke, Andreas and Buness,
Andreas and Chun, Felix K.-H. and Steuber, Thomas and Graefen, Markus
and Simon, Ronald and Sauter, Guido and Poustka, Annemarie and Huland,
Hartwig and Erbersdobler, Andreas and Sültmann, Holger and Hellwinkel,
Olaf J.C.},
title = {Marked Gene Transcript Level Alterations Occur Early During Radical
Prostatectomy},
journal = {European Urology},
year = {2008},
volume = {53},
pages = {333--346},
number = {2},
month = feb,
abstract = {Objectives Gene expression analyses have become an important approach
to understand the biology of cancer. However, transcript level patterns
and RNA quality could rapidly change in response to ischemic and
mechanical stress. Studies have shown that this occurs both perioperatively
and after surgical removal of organs.Methods To better understand
the relative importance of perioperative and postoperative gene expression
changes, we performed quantitative reverse transcription-polymerase
chain reactions on the transcripts of 91 cancer-related genes from
normal and cancerous prostate tissues from 10 patients at eight different
time points during surgical manipulation and after removal of the
prostate.Results The mRNA levels of 8 (EGR1, p21, KRT17, PIM1, S100P,
TNFRSF, WFDC2, and TRIM29) of 91 genes changed significantly with
time of surgery in normal and tumor tissue. Remarkably, all eight
genes were up-regulated, a reaction that was most prominent during
the early intraoperative period. Additional changes occurred but
were much less prominent during the first postoperative hour.Conclusions
Our results substantially challenge the utility of immediate postoperative
tissue sampling. At least for prostate cancer, the data suggest that
preoperative tissue collection by core biopsies is optimal for studying
molecular changes in normal and neoplastic prostate tissues.},
issn = {0302-2838},
keywords = {Degradation, Gene, Gene expression, Ischemia, Prostate cancer, RNA,
Surgery},
url = {http://www.sciencedirect.com/science/article/B6X10-4NFR3YK-1/2/50bc5917f919d03196320cf2bd60f5b4}
}
@ARTICLE{Schlott2005,
author = {Schlott, Thilo and Eiffert, Helmut and Bohne, Wolfgang and Landgrebe,
Jobst and Brunner, Edgar and Spielbauer, Bettina and Knight, Bryan},
title = {Chlamydia trachomatis modulates expression of tumor suppressor gene
caveolin-1 and oncogene C-myc in the transformation zone of non-neoplastic
cervical tissue},
journal = {Gynecologic Oncology},
year = {2005},
volume = {98},
pages = {409--419},
number = {3},
month = sep,
abstract = {Objectives The obligate intracellular bacterium Chlamydia trachomatis
is frequently found in association with benign proliferative, pre-neoplastic
and malignant changes in cervical epithelium. The present study addresses
the possible role of C. trachomatis infection of the uterine cervix
in modulating human cancer gene expression.Methods RNA was extracted
from both C. trachomatis infected and non-infected human fibroblast
cultures treated with ITF[gamma]. The extracted RNA was used for
cDNA microarrays carrying 33,000 human genes to detect abnormal gene
expression induced by Chlamydia. Forty specimens of cervix dissected
from the transformation zone had previously tested negative for HPV
and positive for C. trachomatis by standard DNA PCR (20). These samples
were subjected to RT-PCR to detect the expression of the abnormal
genes induced by Chlamydia infection.Results The ITF[gamma]-induced,
non-replicative Chlamydia-infected fibroblast cultures showed significant
modulation of gene expression. The cultures showed a 2-fold decrease
in the expression of the gene coding for the tumor suppressor caveolin-1,
and increased expression of the oncogene C-myc, a promoter of cervical
carcinogenesis. In tissues from the Chlamydia-infected cervical transformation
zone, real-time RT-PCR demonstrated a highly significant average
4.7-fold reduction of caveolin-1 mRNA (P <= 0.0001) and an average
2.1-fold increase in C-myc (P < 0.05).Conclusions Human ITF[gamma]-treated
fibroblasts as well as non-neoplastic cervical tissues responded
to C. trachomatis with a strong down-regulation of caveolin-1 mRNA
and a light up-regulation of C-myc mRNA. These changes were independent
of the HPV high-risk types. This study reveals possible mechanisms
by which C. trachomatis infection may contribute to neoplastic changes
in the transformation of uterine cervix. These possible mechanisms
require further evaluation.},
issn = {0090-8258},
keywords = {C. trachomatis, Microarray, Real-time RT-PCR, Cervix uteri},
url = {http://www.sciencedirect.com/science/article/B6WG6-4GJV9YR-1/2/a346635c26e53f68d106ae2e1f4ba02d}
}
@ARTICLE{Schlussman2011,
author = {S.D. Schlussman and J. Cassin and Y. Zhang and O. Levran and A. Ho
and M.J. Kreek},
title = {Regional mRNA expression of the endogenous opioid and dopaminergic
systems in brains of C57BL/6J and 129P3/J mice: Strain and heroin
effects},
journal = {Pharmacology Biochemistry and Behavior},
year = {2011},
volume = {100},
pages = {8 - 16},
number = {1},
abstract = {We have previously shown strain and dose differences in heroin-induced
behavior, reward and regional expression of somatostatin receptor
mRNAs in C57BL/6J and 129P3/J mice. Using Real Time PCR we examined
the effects of five doses of heroin on the levels of the transcripts
of endogenous opioid peptides and their receptors and dopaminergic
receptors in the mesocorticolimbic and nigrostriatal pathways in
these same mice. Compared to C57BL/6J animals, 129P3/J mice had higher
mRNA levels of Oprk1 in the nucleus accumbens and of Oprd1 in the
nucleus accumbens and a region containing both the substantia nigra
and ventral tegmental area (SN/VTA). In the cortex of 129P3/J mice,
lower levels of both Oprk1 and Oprd1 mRNAs were observed. Pdyn mRNA
was also lower in the caudate putamen of 129P3/J mice. Strain differences
were not found in the levels of Oprm1, Penk or Pomc mRNAs in any
region examined. Within strains, complex patterns of heroin dose-dependent
changes in the levels of Oprm1, Oprk1 and Oprd1 mRNAs were observed
in the SN/VTA. Additionally, Oprd1 mRNA was dose-dependently elevated
in the hypothalamus. Also in the hypothalamus, we found higher levels
of Drd1a mRNA in C57BL/6J mice than in 129P3/J animals and higher
levels of DAT (Slc6a3) mRNA in the caudate putamen of C57BL/6J animals
than in 129P3/J counterparts. Heroin had dose-related effects on
Drd1a mRNA in the hypothalamus and on Drd2 mRNA in the caudate putamen.},
doi = {10.1016/j.pbb.2011.07.013},
issn = {0091-3057},
keywords = {Endogenous opioid system},
url = {http://www.sciencedirect.com/science/article/pii/S0091305711002498}
}
@ARTICLE{Schlussman2010,
author = {Schlussman, Stefan D. and Cassin, Jared and Levran, Orna and Zhang,
Yong and Ho, Ann and Kreek, Mary Jeanne},
title = {Relative expression of mRNA for the somatostatin receptors in the
caudate putamen of C57BL/6J and 129P3/J mice: Strain and heroin effects},
journal = {Brain Research},
year = {2010},
volume = {1345},
pages = {206--212},
month = jul,
abstract = {Using real time qPCR, we examined the expression of mRNAs for the
five somatostatin receptors (SSTRs) in the caudate putamen of male
C57BL/6J and 129P3/J mice. Animals were exposed to multiple injections
of heroin, or saline, in the setting of a conditioned place preference
study. The relative expression levels of the five SSTR mRNAs differed
between the two strains. In both strains, SSTR-1 mRNA was expressed
at the highest levels and SSTR-5 at the lowest. Interestingly, in
129P3/J mice SSTR-3 mRNA was not detected in the caudate putamen.
We confirmed this finding in the frontal cortex, hypothalamus, nucleus
accumbens and a region containing the substantia nigra and ventral
tegmental area. We also found strain differences in the mRNA levels
of SSTR-2 and -4. Intermittent heroin administration had a dose-dependent
effect on the levels of SSTR-1 and -3 mRNAs. These results demonstrate
strain differences in the expression of specific mRNAs and a heroin-induced
dose-dependent elevation of SSTR-1 and -3 mRNAs in the mouse caudate
putamen.},
issn = {0006-8993},
keywords = {C57BL/6J, 129P3/J, Somatostatin receptor, mRNA},
url = {http://www.sciencedirect.com/science/article/B6SYR-5033XXM-8/2/f05dd615b46b2e333b9b9f4d18a9bcf2}
}
@ARTICLE{Schluter2011,
author = {Schluter, Agatha and Espinosa, Lluis and Fourcade, Stephane and Galino,
Jorge and Lopez, Eva and Ilieva, Ekaterina and Morato, Laia and Asheuer,
Muriel and Cook, Ted and McLaren, Alistair and Reid, Juliet and Kelly,
Fiona and Bates, Stewart and Aubourg, Patrick and Galea, Elena and
Pujol, Aurora},
title = {Functional genomic analysis unravels a metabolic-inflammatory interplay
in adrenoleukodystrophy},
journal = {Hum. Mol. Genet.},
year = {2011},
pages = {ddr536},
abstract = {X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized
by axonopathy and demyelination in the central nervous system and
adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy
(AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain
demyelination (cAMN) and (iii) a childhood variant, cALD, characterized
by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal
fatty acid transporter and subsequent accumulation of very-long-chain
fatty acids (VLCFAs) are the common culprits to all forms of X-ALD,
an aberrant microglial activation accounts for the cerebral forms,
whereas inflammation allegedly plays no role in AMN. How VLCFA accumulation
leads to neurodegeneration and what factors account for the dissimilar
clinical outcomes and prognosis of X-ALD variants remain elusive.
To gain insights into these questions, we undertook a transcriptomic
approach followed by a functional-enrichment analysis in spinal cords
of the animal model of AMN, the Abcd1- null mice, and in normal-appearing
white matter of cAMN and cALD patients. We report that the mouse
model shares with cAMN and cALD a common signature comprising dysregulation
of oxidative phosphorylation, adipocytokine and insulin signaling
pathways, and protein synthesis. Functional validation by quantitative
polymerase chain reaction, western blots and assays in spinal cord
organotypic cultures confirmed the interplay of these pathways through
IkB kinase, being VLCFA in excess a causal, upstream trigger promoting
the altered signature. We conclude that X-ALD is, in all its variants,
a metabolic/inflammatory syndrome, which may offer new targets in
X-ALD therapeutics.},
doi = {10.1093/hmg/ddr536},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/ddr536v2.pdf},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/ddr536v2}
}
@ARTICLE{Schlueter2011,
author = {Schlüter, Holger and Paquet-Fifield, Sophie and Gangatirkar, Pradnya
and Li, Jason and Kaur, Pritinder},
title = {Functional Characterization of Quiescent Keratinocyte Stem Cells
and Their Progeny Reveals a Hierarchical Organization in Human Skin
Epidermis},
journal = {STEM CELLS},
year = {2011},
volume = {29},
pages = {1256--1268},
number = {8},
abstract = {Although homeostatic renewal of human skin epidermis is achieved by
the combined activity of quiescent stem cells (SCs) and their actively
cycling progeny, whether these two populations are equipotent in
their capacity to regenerate tissue has not been determined in biological
assays that mimic lifelong renewal. Using fluorescence activated
cell separation strategy validated previously by us, human epidermis
was fractionated into three distinct subsets: that is, α 6briCD71dim,
α 6briCD71bri, and α 6dim with characteristics of keratinocyte
stem, transient amplifying, and early differentiating cells, respectively.
The global gene expression profile of these fractions was determined
by microarray, confirming that the α 6briCD71dim subset was quiescent,
the α 6briCD71bri was actively cycling, and the α 6dim subset
expressed markers of differentiation. More importantly, functional
evaluation of these populations in an in vivo model for tissue reconstitution
at limiting cell dilutions revealed that the quiescent α 6briCD71dim
fraction was the most potent proliferative and tissue regenerative
population of the epidermis, capable of long-term (LT) epidermal
renewal from as little as 100 cells for up to 10 weeks. In contrast,
the cycling α 6briCD71bri fraction was the first to initiate tissue
reconstitution, although this was not sustained in the LT, while
differentiating α 6dim cells possessed the lowest demonstrable
tissue regenerative capacity. Our data suggest that in human skin,
the epidermal proliferative compartment is not composed of equipotent
cells, but rather is organized in a functionally hierarchical manner
with the most potent quiescent SCs at its apex (i.e., α 6briCD71dim)
followed by cycling progenitors (i.e., α 6briCD71bri) and finally
early differentiating keratinocytes (i.e., α 6dim). STEM CELLS
2011;29:1256–1268},
doi = {10.1002/stem.675},
issn = {1549-4918},
keywords = {Skin, Human, Stem cells, Progenitors, Interfollicular epidermis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/stem.675}
}
@ARTICLE{Schlueter2010,
author = {Schlüter, Jan-Philip and Reinkensmeier, Jan and Daschkey, Svenja
and Evguenieva-Hackenberg, Elena and Janssen, Stefan and Jänicke,
Sebastian and Becker, Jörg and Giegerich, Robert and Becker, Anke},
title = {A genome-wide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium
Sinorhizobium meliloti },
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {245},
number = {1},
abstract = {BACKGROUND:Small untranslated RNAs (sRNAs) are widespread regulators
of gene expression in bacteria. This study reports on a comprehensive
screen for sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium
Sinorhizobium meliloti applying deep sequencing of cDNAs and microarray
hybridizations.RESULTS:A total of 1,125 sRNA candidates that were
classified as trans-encoded sRNAs (173), cis-encoded antisense sRNAs
(117), mRNA leader transcripts (379), and sense sRNAs overlapping
coding regions (456) were identified in a size range of 50 to 348
nucleotides. Among these were transcripts corresponding to 82 previously
reported sRNA candidates. Enrichment for RNAs with primary 5'-ends
prior to sequencing of cDNAs suggested transcriptional start sites
corresponding to 466 predicted sRNA regions. The consensus s70 promoter
motif CTTGAC-N17-CTATAT was found upstream of 101 sRNA candidates.
Expression patterns derived from microarray hybridizations provided
further information on conditions of expression of a number of sRNA
candidates. Furthermore, GenBank, EMBL, DDBJ, PDB, and Rfam databases
were searched for homologs of the sRNA candidates identified in this
study. Searching Rfam family models with over 1,000 sRNA candidates,
re-discovered only those sequences from S. meliloti already known
and stored in Rfam, whereas BLAST searches suggested a number of
homologs in related alpha-proteobacteria.CONCLUSIONS:The screening
data suggests that in S. meliloti about 3% of the genes encode trans-encoded
sRNAs and about 2% antisense transcripts. Thus, this first comprehensive
screen for sRNAs applying deep sequencing in an alpha-proteobacterium
shows that sRNAs also occur in high number in this group of bacteria.},
doi = {10.1186/1471-2164-11-245},
issn = {1471-2164},
pubmedid = {20398411},
url = {http://www.biomedcentral.com/1471-2164/11/245}
}
@ARTICLE{Schlueter2002,
author = {Schlüter, U. and Köpke, D. and Altmann, T. and Müssig, C.},
title = {Analysis of carbohydrate metabolism of CPD antisense plants and the
brassinosteroid-deficient cbb1 mutant},
journal = {Plant, Cell \& Environment},
year = {2002},
volume = {25},
pages = {783--791},
number = {6},
abstract = {Abstract Brassinosteroids (BRs) are essential regulators of growth
and development. BR-deficient mutants such as cpd/cbb3 and dwf4 display
extreme dwarfism due to a failure in cell elongation. To avoid the
severe pleiotropic effects caused by the extreme growth defect, transgenic
Arabidopsis lines carrying a construct for antisense inhibition of
CPD gene expression were established and subjected to physiological
analysis. The CPD-antisense (α-CPD) lines display characteristic
phenotypic alterations of BR-deficient plants such as reduced stem
and petiole growth, smaller leaves, and a slightly delayed development.
The observed changes are intermediate between the corresponding loss-of-function
mutant (cbb3) and wild-type plants. In the present study, the primary
carbon metabolism of the transgenic lines as well as the BR-deficient
cbb1 (dwf1-6/dim) mutant was analysed. Gas exchange measurements
indicated a reduced assimilatory capacity of the α-CPD plants. Soil-grown
α-CPD as well as cbb1 (dwf1-6) mutant plants show a clear reduction
in starch content. The metabolic alterations are accompanied by altered
enzyme activities such as reduced invertase and cytosolic β-amylase
activity, and altered expression patterns of genes such as Atbfruct1,
Asus1, and ct-Bmy (encoding a cell wall invertase, sucrose synthase,
and plastidic β-amylase, respectively). The impaired carbon assimilation,
as well as the altered enzyme activities and gene expression patterns
in the α-CPD and cbb1 (dwf1-6) plants, demonstrate the necessity
of normal CPD and DIM expression for proper carbon uptake and metabolism
and may point to an essential function of BRs. The impaired growth
of BR-deficient plants may be (at least in part) due to reduced photosynthesis.},
issn = {1365-3040},
keywords = {Arabidopsis, brassinosteroids, carbohydrates, CPD, gas exchange},
publisher = {Blackwell Science, Ltd},
url = {http://dx.doi.org/10.1046/j.1365-3040.2002.00860.x}
}
@ARTICLE{Schmalisch2010,
author = {Schmalisch, Matthias and Maiques, Elisa and Nikolov, Lachezar and
Camp, Amy H. and Chevreux, Bastien and Muffler, Andrea and Rodriguez,
Sabrina and Perkins, John and Losick, Richard},
title = {Small Genes under Sporulation Control in the Bacillus subtilis genome},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {5402--5412},
number = {20},
month = oct,
abstract = {Using an oligonucleotide microarray, we searched for previously unrecognized
transcription units in intergenic regions in the genome of Bacillus
subtilis, with an emphasis on identifying small genes activated during
spore formation. Nineteen transcription units were identified, 11
of which were shown to depend on one or more sporulation-regulatory
proteins for their expression. A high proportion of the transcription
units contained small, functional open reading frames (ORFs). One
such newly identified ORF is a member of a family of six structurally
similar genes that are transcribed under the control of sporulation
transcription factor {sigma}E or {sigma}K. A multiple mutant lacking
all six genes was found to sporulate with slightly higher efficiency
than the wild type, suggesting that under standard laboratory conditions
the expression of these genes imposes a small cost on the production
of heat-resistant spores. Finally, three of the transcription units
specified small, noncoding RNAs; one of these was under the control
of the sporulation transcription factor {sigma}E, and another was
under the control of the motility sigma factor {sigma}D.},
url = {http://jb.asm.org/cgi/content/abstract/192/20/5402}
}
@ARTICLE{Schmelzer2010,
author = {Schmelzer, Constance and Döring, Frank},
title = {Identification of LPS-inducible genes downregulated by ubiquinone
in human THP-1 monocytes},
journal = {BioFactors},
year = {2010},
volume = {36},
pages = {222--228},
number = {3},
abstract = {Abstract 10.1002/biof.93.abs Coenzyme Q10 (CoQ10) is an obligatory
element in the respiratory chain and functions as a potent antioxidant
of lipid membranes. More recently, anti-inflammatory effects as well
as an impact of CoQ10 on gene expression have been observed. To reveal
putative effects of Q10 on LPS-induced gene expression, whole genome
expression analysis was performed in the monocytic cell line THP-1.
Thousand one hundred twenty-nine and 710 probe sets have been identified
to be significantly (P ≤ 0.05) up and downregulated in LPS-treated
cells when compared with controls, respectively. Text mining analysis
of the top 50 LPS upregulated genes revealed a functional connection
in the NFκB pathway and confirmed our applied in vitro stimulation
model. Moreover, 33 LPS-sensitive genes have been identified to be
significantly downregulated by Q10-treatment between a factor of
1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve
genes a primary involvement in protein metabolism (e.g., HERC1 and
EPS15), cell proliferation (e.g., CCDC100 and SMURF1), and transcriptional
processes (e.g., CNOT4 and STK4). Three genes were either related
to NFκB transcription factor activity (ERC1), cytokinesis (DIAPH2),
or modulation of oxidative stress (MSRA). In conclusion, our data
provide evidence that Q10 downregulates LPS-inducible genes in the
monocytic cell line THP-1. Thus, the previously described effects
of Q10 on the reduction of proinflammatory mediators might be due
to its antioxidant impact on gene expression.},
issn = {1872-8081},
keywords = {CoQ10, gene expression, inflammation, monocytes, LPS},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/biof.93}
}
@ARTICLE{Schmid2007,
author = {Schmid, Andreas and Sutto, Zoltan and Nlend, Marie-Christine and
Horvath, Gabor and Schmid, Nathalie and Buck, Jochen and Levin, Lonny
R. and Conner, Gregory E. and Fregien, Nevis and Salathe, Matthias},
title = {Soluble Adenylyl Cyclase Is Localized to Cilia and Contributes to
Ciliary Beat Frequency Regulation via Production of cAMP},
journal = {J. Gen. Physiol.},
year = {2007},
volume = {130},
pages = {99--109},
number = {1},
month = jul,
abstract = {Ciliated airway epithelial cells are subject to sustained changes
in intracellular CO2/HCO3- during exacerbations of airway diseases,
but the role of CO2/HCO3--sensitive soluble adenylyl cyclase (sAC)
in ciliary beat regulation is unknown. We now show not only sAC expression
in human airway epithelia (by RT-PCR, Western blotting, and immunofluorescence)
but also its specific localization to the axoneme (Western blotting
and immunofluorescence). Real time estimations of [cAMP] changes
in ciliated cells, using FRET between fluorescently tagged PKA subunits
(expressed under the foxj1 promoter solely in ciliated cells), revealed
CO2/HCO3--mediated cAMP production. This cAMP production was specifically
blocked by sAC inhibitors but not by transmembrane adenylyl cyclase
(tmAC) inhibitors. In addition, this cAMP production stimulated ciliary
beat frequency (CBF) independently of intracellular pH because PKA
and sAC inhibitors were uniquely able to block CO2/HCO3--mediated
changes in CBF (while tmAC inhibitors had no effect). Thus, sAC is
localized to motile airway cilia and it contributes to the regulation
of human airway CBF. In addition, CO2/HCO3- increases indeed reversibly
stimulate intracellular cAMP production by sAC in intact cells.},
url = {http://jgp.rupress.org/cgi/content/abstract/130/1/99}
}
@ARTICLE{Schmid2011,
author = {Schmid, Amy K. and Pan, Min and Sharma, Kriti and Baliga, Nitin S.},
title = {Two transcription factors are necessary for iron homeostasis in a
salt-dwelling archaeon},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {2519--2533},
number = {7},
month = apr,
abstract = {Because iron toxicity and deficiency are equally life threatening,
maintaining intracellular iron levels within a narrow optimal range
is critical for nearly all known organisms. However, regulatory mechanisms
that establish homeostasis are not well understood in organisms that
dwell in environments at the extremes of pH, temperature, and salinity.
Under conditions of limited iron, the extremophile Halobacterium
salinarum, a salt-loving archaeon, mounts a specific response to
scavenge iron for growth. We have identified and characterized the
role of two transcription factors (TFs), Idr1 and Idr2, in regulating
this important response. An integrated systems analysis of TF knockout
gene expression profiles and genome-wide binding locations in the
presence and absence of iron has revealed that these TFs operate
collaboratively to maintain iron homeostasis. In the presence of
iron, Idr1 and Idr2 bind near each other at 24 loci in the genome,
where they are both required to repress some genes. By contrast,
Idr1 and Idr2 are both necessary to activate other genes in a putative
a feed forward loop. Even at loci bound independently, the two TFs
target different genes with similar functions in iron homeostasis.
We discuss conserved and unique features of the Idr1-Idr2 system
in the context of similar systems in organisms from other domains
of life.},
comment = {10.1093/nar/gkq1211},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/7/2519}
}
@ARTICLE{Schmid2010,
author = {Schmid, Fabian and Glaus, Esther and Cremers, Frans P. M. and Kloeckener-Gruissem,
Barbara and Berger, Wolfgang and Neidhardt, John},
title = {Mutation- and Tissue-Specific Alterations of RPGR Transcripts},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {1628--1635},
number = {3},
month = mar,
abstract = {Purpose.The majority of patients with X chromosome-linked retinitis
pigmentosa (XlRP) carry mutations in the RPGR gene. The authors studied
whether patients with RPGR mutations show additional splice defects
that may interfere with RPGR properties. Methods.Patient-derived
cell lines with RPGR mutations were raised in suspension. To verify
mutations, direct sequencing of PCR products was performed. Patient-specific
alterations in RPGR splicing were analyzed by RT-PCR and confirmed
by sequencing. Tissue-specific expression levels of RPGR splice variants
were quantified by real-time PCR using pools of different human donor
tissues. Results.The authors analyzed the splicing of RPGR in seven
RP patient-derived lymphoblastoid cell lines carrying hemizygous
RPGR mutations. In three patient cell lines, they identified and
characterized splice defects that were present in addition to a mutation.
These splice defects were likely to interfere with normal RPGR properties.
Furthermore, they identified four novel RPGR transcripts, either
containing a new exon termed 11a or skipping the constitutive exons
12, 14, and 15. Novel and known RPGR isoforms were found to be differentially
regulated in several human tissues. In human retina, approximately
10% of RPGR transcripts are alternatively spliced between exons 9
and 15. Conclusions.These findings show that splicing of RPGR is
precisely regulated in a tissue-dependent fashion and suggest that
mutations in RPGR frequently interfere with the expression of alternative
transcript isoforms. These results implicate the importance of RPGR
transcript analysis in patients with RP. The authors further discuss
RPGR splicing as a modifier of different disease phenotypes described
in patients with XlRP.},
url = {http://www.iovs.org/cgi/content/abstract/51/3/1628}
}
@ARTICLE{Schmid2010a,
author = {Schmid, Ramona and Baum, Patrick and Ittrich, Carina and Fundel-Clemens,
Katrin and Huber, Wolfgang and Brors, Benedikt and Eils, Roland and
Weith, Andreas and Mennerich, Detlev and Quast, Karsten},
title = {Comparison of normalization methods for Illumina BeadChip HumanHT-12
v3},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {349},
number = {1},
abstract = {BACKGROUND:Normalization of microarrays is a standard practice to
account for and minimize effects which are not due to the controlled
factors in an experiment. There is an overwhelming number of different
methods that can be applied, none of which is ideally suited for
all experimental designs. Thus, it is important to identify a normalization
method appropriate for the experimental setup under consideration
that is neither too negligent nor too stringent. Major aim is to
derive optimal results from the underlying experiment. Comparisons
of different normalization methods have already been conducted, none
of which, to our knowledge, comparing more than a handful of methods.RESULTS:In
the present study, 25 different ways of pre-processing Illumina Sentrix
BeadChip array data are compared. Among others, methods provided
by the BeadStudio software are taken into account. Looking at different
statistical measures, we point out the ideal versus the actual observations.
Additionally, we compare qRT-PCR measurements of transcripts from
different ranges of expression intensities to the respective normalized
values of the microarray data. Taking together all different kinds
of measures, the ideal method for our dataset is identified.CONCLUSIONS:Pre-processing
of microarray gene expression experiments has been shown to influence
further downstream analysis to a great extent and thus has to be
carefully chosen based on the design of the experiment. This study
provides a recommendation for deciding which normalization method
is best suited for a particular experimental setup.},
doi = {10.1186/1471-2164-11-349},
issn = {1471-2164},
pubmedid = {20525181},
url = {http://www.biomedcentral.com/1471-2164/11/349}
}
@ARTICLE{Schmiderer2010,
author = {Schmiderer, Corinna and Grausgruber-Gröger, Sabine and Grassi, Paolo
and Steinborn, Ralf and Novak, Johannes},
title = {Influence of gibberellin and daminozide on the expression of terpene
synthases and on monoterpenes in common sage (Salvia officinalis)},
journal = {Journal of Plant Physiology},
year = {2010},
volume = {167},
pages = {779--786},
number = {10},
month = jul,
abstract = {Common sage (Salvia officinalis L., Lamiaceae) is one of the most
important medicinal and aromatic plants, with antioxidant, antimicrobial,
spasmolytic, astringent, antihidrotic and specific sensorial properties.
The essential oil of the plant, composed mainly of the monoterpenes
1,8-cineole, [alpha]-thujone, [beta]-thujone and camphor, is responsible
for some of these effects. Gibberellins regulate diverse physiological
processes in plants, such as seed germination, shoot elongation and
cell division. In this study, we analyzed the effect of exogenously
applied plant growth regulators, namely gibberellic acid (GA3) and
daminozide, on leaf morphology and essential oil formation of two
leaf stages during the period of leaf expansion. Essential oil content
increased with increasing levels of gibberellins and decreased when
gibberellin biosynthesis was blocked with daminozide. With increasing
levels of gibberellins, 1,8-cineole and camphor contents increased.
Daminozide blocked the accumulation of [alpha]- and [beta]-thujone.
GA3 at the highest level applied also led to a significant decrease
of [alpha]- and [beta]-thujone. Monoterpene synthases are a class
of enzymes responsible for the first step in monoterpene biosynthesis,
competing for the same substrate geranylpyrophosphate. The levels
of gene expression of the three most important monoterpene synthases
in sage were investigated, 1,8-cineole synthase leading directly
to 1,8-cineole, (+)-sabinene synthase responsible for the first step
in the formation of [alpha]- and [beta]-thujone, and (+)-bornyl diphosphate
synthase, the first step in camphor biosynthesis. The foliar application
of GA3 increased, while daminozide significantly decreased gene expression
of the monoterpene synthases. The amounts of two of the end products,
1,8-cineole and camphor, were directly correlated with the levels
of gene expression of the respective monoterpene synthases, indicating
transcriptional control, while the formation of [alpha]- and [beta]-thujone
was not transcriptionally regulated.},
issn = {0176-1617},
keywords = {Daminozide, Gene expression, Gibberellin, Salvia officinalis, Terpene
synthases},
url = {http://www.sciencedirect.com/science/article/B7GJ7-4YD9X8C-1/2/6d3db023eab3f95126c092798ec56675}
}
@ARTICLE{Schmidl2009,
author = {Schmidl, Christian and Klug, Maja and Boeld, Tina J. and Andreesen,
Reinhard and Hoffmann, Petra and Edinger, Matthias and Rehli, Michael},
title = {Lineage-specific DNA methylation in T cells correlates with histone
methylation and enhancer activity},
journal = {Genome Res.},
year = {2009},
volume = {19},
pages = {1165--1174},
number = {7},
month = jul,
abstract = {DNA methylation participates in establishing and maintaining chromatin
structures and regulates gene transcription during mammalian development
and cellular differentiation. With few exceptions, research thus
far has focused on gene promoters, and little is known about the
extent, functional relevance, and regulation of cell type-specific
DNA methylation at promoter-distal sites. Here, we present a comprehensive
analysis of differential DNA methylation in human conventional CD4+
T cells (Tconv) and CD4+CD25+ regulatory T cells (Treg), cell types
whose differentiation and function are known to be controlled by
epigenetic mechanisms. Using a novel approach that is based on the
separation of a genome into methylated and unmethylated fractions,
we examined the extent of lineage-specific DNA methylation across
whole gene loci. More than 100 differentially methylated regions
(DMRs) were identified that are present mainly in cell type-specific
genes (e.g., FOXP3, IL2RA, CTLA4, CD40LG, and IFNG) and show differential
patterns of histone H3 lysine 4 methylation. Interestingly, the majority
of DMRs were located at promoter-distal sites, and many of these
areas harbor DNA methylation-dependent enhancer activity in reporter
gene assays. Thus, our study provides a comprehensive, locus-wide
analysis of lineage-specific methylation patterns in Treg and Tconv
cells, links cell type-specific DNA methylation with histone methylation
and regulatory function, and identifies a number of cell type-specific,
CpG methylation-sensitive enhancers in immunologically relevant genes.},
url = {http://genome.cshlp.org/cgi/content/abstract/19/7/1165}
}
@ARTICLE{Schmidt2005,
author = {Schmidt, Andrew J. and Ryjenkov, Dmitri A. and Gomelsky, Mark},
title = {The Ubiquitous Protein Domain EAL Is a Cyclic Diguanylate-Specific
Phosphodiesterase: Enzymatically Active and Inactive EAL Domains},
journal = {J. Bacteriol.},
year = {2005},
volume = {187},
pages = {4774--4781},
number = {14},
month = jul,
abstract = {The EAL domain (also known as domain of unknown function 2 or DUF2)
is a ubiquitous signal transduction protein domain in the Bacteria.
Its involvement in hydrolysis of the novel second messenger cyclic
dimeric GMP (c-di-GMP) was demonstrated in vivo but not in vitro.
The EAL domain-containing protein Dos from Escherichia coli was reported
to hydrolyze cyclic AMP (cAMP), implying that EAL domains have different
substrate specificities. To investigate the biochemical activity
of EAL, the E. coli EAL domain-containing protein YahA and its individual
EAL domain were overexpressed, purified, and characterized in vitro.
Both full-length YahA and the EAL domain hydrolyzed c-di-GMP into
linear dimeric GMP, providing the first biochemical evidence that
the EAL domain is sufficient for phosphodiesterase activity. This
activity was c-di-GMP specific, optimal at alkaline pH, dependent
on Mg2+ or Mn2+, strongly inhibited by Ca2+, and independent of protein
oligomerization. Linear dimeric GMP was shown to be 5'pGpG. The EAL
domain from Dos was overexpressed, purified, and found to function
as a c-di-GMP-specific phosphodiesterase, not as a cAMP-specific
phosphodiesterase, in contrast to previous reports. The EAL domains
can hydrolyze 5'pGpG into GMP, however, very slowly, thus implying
that this activity is irrelevant in vivo. Therefore, c-di-GMP is
the exclusive substrate of EAL. Multiple-sequence alignment revealed
two groups of EAL domains hypothesized to correspond to enzymatically
active and inactive domains. The domains in the latter group have
mutations in residues conserved in the active domains. The enzymatic
inactivity of EAL domains may explain their coexistence with GGDEF
domains in proteins possessing c-di-GMP synthase (diguanulate cyclase)
activity.},
url = {http://jb.asm.org/cgi/content/abstract/187/14/4774}
}
@ARTICLE{Schmidt2009,
author = {Schmidt, Dominic and Wilson, Michael D. and Spyrou, Christiana and
Brown, Gordon D. and Hadfield, James and Odom, Duncan T.},
title = {ChIP-seq: Using high-throughput sequencing to discover protein-DNA
interactions},
journal = {Methods},
year = {2009},
volume = {48},
pages = {240--248},
number = {3},
month = jul,
abstract = {Chromatin immunoprecipitation (ChIP) allows specific protein-DNA interactions
to be isolated. Combining ChIP with high-throughput sequencing reveals
the DNA sequence involved in these interactions. Here, we describe
how to perform ChIP-seq starting with whole tissues or cell lines,
and ending with millions of short sequencing tags that can be aligned
to the reference genome of the species under investigation. We also
outline additional procedures to recover ChIP-chip libraries for
ChIP-seq and discuss contemporary issues in data analysis.},
booktitle = {Global approaches to study gene regulation},
issn = {1046-2023},
keywords = {ChIPseq, ChIP-seq, Chromatin immunoprecipitation, High-throughput
sequencing},
url = {http://www.sciencedirect.com/science/article/B6WN5-4VT14H0-2/2/c91dc87927c4d544ee0cf12cf292040a}
}
@ARTICLE{Schmidt2011a,
author = {Schmidt, Jonathan A. and Abramowitz, Lara K. and Kubota, Hiroshi
and Wu, Xin and Niu, Zhiyv and Avarbock, Mary R. and Tobias, John
W. and Bartolomei, Marisa S. and Brinster, Ralph L.},
title = {In Vivo and In Vitro Aging Is Detrimental to Mouse Spermatogonial
Stem Cell Function},
journal = {Biol Reprod},
year = {2011},
volume = {84},
pages = {698--706},
number = {4},
month = apr,
abstract = {The development of techniques to maintain the spermatogonial stem
cell (SSC) in vivo and in vitro for extended periods essentially
allows for the indefinite continuation of an individual germline.
Recent evidence indicates that the aging of male reproductive function
is due to failure of the SSC niche. SSCs are routinely cultured for
6 mo, and no apparent effect of culture over this period has been
observed. To determine the effects of SSC aging, we utilized an in
vitro culture system, followed by quantitative transplantation experiments.
After culture for 6 mo, SSCs that had been aged in vivo for 1500
days had a slower proliferation rate than SSCs that were aged in
vivo to 8 or 300 days. Examination of methylation patterns revealed
no apparent difference in DNA methylation between SSCs that were
aged 8, 300, or 1500 days before culture. Long-term culture periods
resulted in a loss of stem cell potential without an obvious change
in the visual appearance of the culture. DNA microarray analysis
of in vivo- and in vitro-aged SSCs identified the differential expression
of several genes important for SSC function, including B-cell CLL/lymphoma
6, member B (Bcl6b), Lim homeobox protein 1 (Lhx1), and thymus cell
antigen 1, theta (Thy1). Collectively, these data indicate that,
although both in vitro and in vivo aging are detrimental to SSC function,
in vitro aging results in greater loss of function, potentially due
to a decrease in core SSC self-renewal gene expression and an increase
in germ cell differentiation gene expression.},
comment = {10.1095/biolreprod.110.088229},
url = {http://www.biolreprod.org/cgi/content/abstract/84/4/698}
}
@ARTICLE{Schmidt2011b,
author = {Schmidt, Lotte M. and Belvisi, Maria G. and Bode, Konrad A. and Bauer,
Judith and Schmidt, Claudia and Suchy, Maria-Theresia and Tsikas,
Dimitrios and Scheuerer, Jutta and Lasitschka, Felix and Grone, Herman-Josef
and Dalpke, Alexander H.},
title = {Bronchial Epithelial Cell-Derived Prostaglandin E2 Dampens the Reactivity
of Dendritic Cells},
journal = {J. Immunol.},
year = {2011},
volume = {186},
pages = {2095--2105},
number = {4},
month = feb,
abstract = {Airway epithelial cells regulate immune reactivity of local dendritic
cells (DCs), thus contributing to microenvironment homeostasis. In
this study, we set out to identify factors that mediate this regulatory
interaction. We show that tracheal epithelial cells secrete soluble
factors that downregulate TNF-{alpha} and IL-12p40 secretion by bone
marrow-derived DCs but upregulate IL-10 and arginase-1. Size exclusion
chromatography identified small secreted molecules having high modulatory
activity on DCs. We observed that airway tracheal epithelial cells
constitutively release the lipid mediator PGE2. Blocking the synthesis
of PGs within airway epithelial cells relieved DCs from inhibition.
Cyclooxygenase-2 was found to be expressed in primary tracheal epithelial
cell cultures in vitro and in vivo as shown by microdissection of
epithelial cells followed by real-time PCR. Paralleling these findings
we observed that DCs treated with an antagonist for E-prostanoid
4 receptor as well as DCs lacking E-prostanoid 4 receptor showed
reduced inhibition by airway epithelial cells with respect to secretion
of proinflammatory cytokines measured by ELISA. Furthermore, PGE2
mimicked the effects of epithelial cells on DCs. The results indicate
that airway epithelial cell-derived PGE2 contributes to the modulation
of DCs under homeostatic conditions.},
comment = {10.4049/jimmunol.1002414},
url = {http://www.jimmunol.org/cgi/content/abstract/186/4/2095}
}
@ARTICLE{Schmidt2011,
author = {Schmidt, Monica A. and Barbazuk, W. Brad and Sandford, Michael and
May, Greg and Song, Zhihong and Zhou, Wenxu and Nikolau, Basil J.
and Herman, Eliot M.},
title = {Silencing of Soybean Seed Storage Proteins Results in a Rebalanced
Protein Composition Preserving Seed Protein Content without Major
Collateral Changes in the Metabolome and Transcriptome},
journal = {Plant Physiology},
year = {2011},
volume = {156},
pages = {330--345},
number = {1},
month = may,
abstract = {The ontogeny of seed structure and the accumulation of seed storage
substances is the result of a determinant genetic program. Using
RNA interference, the synthesis of soybean (Glycine max) glycinin
and conglycinin storage proteins has been suppressed. The storage
protein knockdown (SP-) seeds are overtly identical to the wild type,
maturing to similar size and weight, and in developmental ontogeny.
The SP- seeds rebalance the proteome, maintaining wild-type levels
of protein and storage triglycerides. The SP- soybeans were evaluated
with systems biology techniques of proteomics, metabolomics, and
transcriptomics using both microarray and next-generation sequencing
transcript sequencing (RNA-Seq). Proteomic analysis shows that rebalancing
of protein content largely results from the selective increase in
the accumulation of only a few proteins. The rebalancing of protein
composition occurs with small alterations to the seed's transcriptome
and metabolome. The selectivity of the rebalancing was further tested
by introgressing into the SP- line a green fluorescent protein (GFP)
glycinin allele mimic and quantifying the resulting accumulation
of GFP. The GFP accumulation was similar to the parental GFP-expressing
line, showing that the GFP glycinin gene mimic does not participate
in proteome rebalancing. The results show that soybeans make large
adjustments to the proteome during seed filling and compensate for
the shortage of major proteins with the increased selective accumulation
of other proteins that maintains a normal protein content.},
comment = {10.1104/pp.111.173807},
url = {http://www.plantphysiol.org/cgi/content/abstract/156/1/330}
}
@ARTICLE{Schmidt2008,
author = {Schmidt, Marcus and Bohm, Daniel and von Torne, Christian and Steiner,
Eric and Puhl, Alexander and Pilch, Henryk and Lehr, Hans-Anton and
Hengstler, Jan G. and Kolbl, Heinz and Gehrmann, Mathias},
title = {The Humoral Immune System Has a Key Prognostic Impact in Node-Negative
Breast Cancer},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {5405--5413},
number = {13},
month = jul,
abstract = {Estrogen receptor (ER) expression and proliferative activity are established
prognostic factors in breast cancer. In a search for additional prognostic
motifs, we analyzed the gene expression patterns of 200 tumors of
patients who were not treated by systemic therapy after surgery using
a discovery approach. After performing hierarchical cluster analysis,
we identified coregulated genes related to the biological process
of proliferation, steroid hormone receptor expression, as well as
B-cell and T-cell infiltration. We calculated metagenes as a surrogate
for all genes contained within a particular cluster and visualized
the relative expression in relation to time to metastasis with principal
component analysis. Distinct patterns led to the hypothesis of a
prognostic role of the immune system in tumors with high expression
of proliferation-associated genes. In multivariate Cox regression
analysis, the proliferation metagene showed a significant association
with metastasis-free survival of the whole discovery cohort [hazard
ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40-3.46]. The
B-cell metagene showed additional independent prognostic information
in carcinomas with high proliferative activity (HR, 0.66; 95% CI,
0.46-0.97). A prognostic influence of the B-cell metagene was independently
confirmed by multivariate analysis in a first validation cohort enriched
for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62-0.98) and
a second validation cohort enriched for younger patients (n = 302;
HR, 0.83; 95% CI, 0.7-0.97). Thus, we could show in three cohorts
of untreated, node-negative breast cancer patients that the humoral
immune system plays a pivotal role in metastasis-free survival of
carcinomas of the breast. [Cancer Res 2008;68(13):5405-13]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/13/5405}
}
@ARTICLE{Schmidt2010a,
author = {Schmidt, Mathias V. and Trumbach, Dietrich and Weber, Peter and Wagner,
Klaus and Scharf, Sebastian H. and Liebl, Claudia and Datson, Nicole
and Namendorf, Christian and Gerlach, Tamara and Kuhne, Claudia and
Uhr, Manfred and Deussing, Jan M. and Wurst, Wolfgang and Binder,
Elisabeth B. and Holsboer, Florian and Muller, Marianne B.},
title = {Individual Stress Vulnerability Is Predicted by Short-Term Memory
and AMPA Receptor Subunit Ratio in the Hippocampus},
journal = {J. Neurosci.},
year = {2010},
volume = {30},
pages = {16949--16958},
number = {50},
month = dec,
abstract = {Increased vulnerability to aversive experiences is one of the main
risk factors for stress-related psychiatric disorders as major depression.
However, the molecular bases of vulnerability, on the one hand, and
stress resilience, on the other hand, are still not understood. Increasing
clinical and preclinical evidence suggests a central involvement
of the glutamatergic system in the pathogenesis of major depression.
Using a mouse paradigm, modeling increased stress vulnerability and
depression-like symptoms in a genetically diverse outbred strain,
and we tested the hypothesis that differences in AMPA receptor function
may be linked to individual variations in stress vulnerability. Vulnerable
and resilient animals differed significantly in their dorsal hippocampal
AMPA receptor expression and AMPA receptor binding. Treatment with
an AMPA receptor potentiator during the stress exposure prevented
the lasting effects of chronic social stress exposure on physiological,
neuroendocrine, and behavioral parameters. In addition, spatial short-term
memory, an AMPA receptor-dependent behavior, was found to be predictive
of individual stress vulnerability and response to AMPA potentiator
treatment. Finally, we provide evidence that genetic variations in
the AMPA receptor subunit GluR1 are linked to the vulnerable phenotype.
Therefore, we propose genetic variations in the AMPA receptor system
to shape individual stress vulnerability. Those individual differences
can be predicted by the assessment of short-term memory, thereby
opening up the possibility for a specific treatment by enhancing
AMPA receptor function.},
comment = {10.1523/JNEUROSCI.4668-10.2010},
url = {http://www.jneurosci.org/cgi/content/abstract/30/50/16949}
}
@ARTICLE{Schmidt2010,
author = {Schmidt, Nicole and Gonzalez, Erik and Visekruna, Alexander and Kuhl,
Anja A and Loddenkemper, Christoph and Mollenkopf, Hans and Kaufmann,
Stefan H E and Steinhoff, Ulrich and Joeris, Thorsten},
title = {Targeting the proteasome: partial inhibition of the proteasome by
bortezomib or deletion of the immunosubunit LMP7 attenuates experimental
colitis},
journal = {Gut},
year = {2010},
volume = {59},
pages = {896--906},
number = {7},
month = jul,
abstract = {Background and aimsInflammatory bowel disease (IBD), comprising Crohns
disease and ulcerative colitis, is characterised by chronic relapsing
inflammation of the gut. Increased proteasome activity, associated
with the expression of immunoproteasomes, was found to enhance proinflammatory
signalling and thus promotes inflammation in patients with IBD. The
aim of this study was to explore whether modulation of the proteasomal
activity is a suitable therapeutic approach to limit inflammation
in colitis. MethodsThis concept was assessed in two different experimental
set-ups. Development of dextran sodium sulfate (DSS)-induced colitis
was tested (1) in lmp7-/- mice lacking the immunoproteasome subunit
LMP7 and (2) in wild-type (WT) mice treated with the proteasome inhibitor
bortezomib. ResultsCompared with WT mice, lmp7-/- mice develop significantly
attenuated colitis due to reduced nuclear factor-{kappa}B (NF-{kappa}B)
signalling in the absence of LMP7. Further, treatment with bortezomib
revealed dose-dependent amelioration of DSS-induced inflammation.
In both approaches modulation of the proteasome activity limited
the secretion of proinflammatory cytokines and chemokines. Consequently,
infiltration of the colon by neutrophils and expansion of inflammatory
T helper 1 (Th1) and Th17 T cells was diminished and thus prevented
excessive tissue damage. ConclusionsIt was demonstrated that modulation
of the proteasome activity is effective in attenuating experimental
colitis. The results reveal that reduction of the proteasome activity
either by partial inhibition with bortezomib or by specifically targeting
the immunoproteasome subunit LMP7 is a suitable treatment of intestinal
inflammation.},
url = {http://gut.bmj.com/cgi/content/abstract/59/7/896}
}
@ARTICLE{Schmidt2006,
author = {Schmidt, Stefan and Rainer, Johannes and Riml, Stefan and Ploner,
Christian and Jesacher, Simone and Achmuller, Clemens and Presul,
Elisabeth and Skvortsov, Sergej and Crazzolara, Roman and Fiegl,
Michael and Raivio, Taneli and Janne, Olli A. and Geley, Stephan
and Meister, Bernhard and Kofler, Reinhard},
title = {Identification of glucocorticoid-response genes in children with
acute lymphoblastic leukemia},
journal = {Blood},
year = {2006},
volume = {107},
pages = {2061--2069},
number = {5},
month = mar,
abstract = {The ability of glucocorticoids (GCs) to kill lymphoid cells led to
their inclusion in essentially all chemotherapy protocols for lymphoid
malignancies, particularly childhood acute lymphoblastic leukemia
(ALL). GCs mediate apoptosis via their cognate receptor and subsequent
alterations in gene expression. Previous investigations, including
expression profiling studies with subgenome microarrays in model
systems, have led to a number of attractive, but conflicting, hypotheses
that have never been tested in a clinical setting. Here, we present
a comparative whole-genome expression profiling approach using lymphoblasts
(purified at 3 time points) from 13 GC-sensitive children undergoing
therapy for ALL. For comparisons, expression profiles were generated
from an adult patient with ALL, peripheral blood lymphocytes from
GC-exposed healthy donors, GC-sensitive and -resistant ALL cell lines,
and mouse thymocytes treated with GCs in vivo and in vitro. This
generated an essentially complete list of GC-regulated candidate
genes in clinical settings and experimental systems, allowing immediate
analysis of any gene for its potential significance to GC-induced
apoptosis. Our analysis argued against most of the model-based hypotheses
and instead identified a small number of novel candidate genes, including
PFKFB2, a key regulator of glucose metabolism; ZBTB16, a putative
transcription factor; and SNF1LK, a protein kinase implicated in
cell-cycle regulation.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/107/5/2061}
}
@ARTICLE{Schmidt2004,
author = {Schmidt, Susanne M. and Schag, Kerstin and Muller, Martin R. and
Weinschenk, Toni and Appel, Silke and Schoor, Oliver and Weck, Markus
M. and Grunebach, Frank and Kanz, Lothar and Stevanovic, Stefan and
Rammensee, Hans-Georg and Brossart, Peter},
title = {Induction of Adipophilin-Specific Cytotoxic T Lymphocytes Using a
Novel HLA-A2-Binding Peptide That Mediates Tumor Cell Lysis},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {1164--1170},
number = {3},
month = feb,
abstract = {Identification of tumor-associated antigens and advances in tumor
immunology resulted in the development of vaccination strategies
to treat patients with malignant diseases. Using a novel approach
that combines DNA chip analysis of tumor samples with isolation of
peptides on the surface of tumor cells, a HLA-A*0201-binding peptide
derived from the adipophilin protein was identified. Adipophilin
is involved in lipid storage and was thought to be expressed only
in adipocytes, but it can be found in other cell types such as macrophages
or tumor cells. In the present study, we analyzed the possible use
of this peptide as a T-cell epitope presented by malignant cells.
To accomplish this, we induced CTL responses using this HLA-A*0201-binding
peptide. The in vitro-induced CTLs efficiently lysed cells pulsed
with the adipophilin peptide and HLA-matched tumor cell lines in
an antigen-specific and HLA-restricted manner. Finally, the induced
CTLs recognized autologous dendritic cells (DCs) pulsed with the
antigenic peptide or transfected with tumor RNA purified from an
adipophilin-expressing tumor cell line. To further analyze the possible
use of this peptide in immunotherapies of human malignancies, we
induced adipophilin-specific CTLs using peripheral blood mononuclear
cells and DCs from HLA-A*0201-positive patients with chronic lymphatic
leukemia and plasma cell leukemia. The in vitro-generated CTLs recognized
autologous chronic lymphatic leukemia cells and malignant plasma
cells, whereas they spared nonmalignant resting or activated B and
T lymphocytes, monocytes, or DCs. Our results demonstrate that this
peptide might represent an interesting candidate for the development
of cancer vaccines designed to target adipophilin-derived epitopes
in a wide range of malignancies.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/3/1164}
}
@ARTICLE{Schmidt2008a,
author = {Schmidt, Valentina A. and Chiariello, Carmine S. and Capilla, Encarnacion
and Miller, Frederick and Bahou, Wadie F.},
title = {Development of Hepatocellular Carcinoma in Iqgap2-Deficient Mice
Is IQGAP1 Dependent},
journal = {Mol. Cell. Biol.},
year = {2008},
volume = {28},
pages = {1489--1502},
number = {5},
month = mar,
abstract = {IQGAPs are multidomain scaffolding proteins that integrate Rho GTPase
and Ca2+/calmodulin signals with cell adhesive and cytoskeletal reorganizational
events. Targeted disruption of the murine Iqgap2 gene resulted in
the age-dependent development of apoptosis and hepatocellular carcinoma
(HCC), characterized by the overexpression of IQGAP1, the loss of
membrane E-cadherin expression, the cytoplasmic translocation (and
activation) of {beta}-catenin, and the overexpression of a nuclear
target of {beta}-catenin, cyclin D1. In normal hepatocytes, IQGAP2
was found to exist as one component of a multifunctional scaffolding
complex comprising IQGAP1, {beta}-catenin, and E-cadherin, with no
evidence for direct IQGAP1-IQGAP2 interactions. Interbreeding of
Iqgap2-/- mice into the Iqgap1-/- background resulted in the phenotypic
correction of the preexisting hepatopathy, decreases in the incidence
and sizes of HCC tumors, and the normalization of overall survival
rates compared to those of Iqgap2-/- mice, suggesting that maximal
penetrance of the Iqgap2-/- HCC phenotype requires the coordinate
expression of IQGAP1. These results identify Iqgap2 as a novel tumor
suppressor gene specifically linked to the development of HCC and
the activation of the Wnt/{beta}-catenin signaling pathway, while
also suggesting that IQGAP1 and IQGAP2 retain functionally divergent
roles in hepatocellular carcinogenesis.},
url = {http://mcb.asm.org/cgi/content/abstract/28/5/1489}
}
@ARTICLE{Schmidt2004a,
author = {Schmidt, Wolfgang M. and Kalipciyan, Maria and Dornstauder, Eva and
Rizovski, Blanka and Steger, Guenther G. and Sedivy, Roland and Mueller,
Manfred W. and Mader, Robert M.},
title = {Dissecting progressive stages of 5-fluorouracil resistance in vitro
using RNA expression profiling},
journal = {Int. J. Cancer},
year = {2004},
volume = {112},
pages = {200--212},
number = {2},
abstract = {Abstract 10.1002/ijc.20401.abs Resistance to anticancer drugs such
as the widely used antimetabolite 5-fluorouracil (FU) is one of the
most important obstacles to cancer chemotherapy. Using GeneChip arrays,
we compared the expression profile of different stages of FU resistance
in colon cancer cells after in vitro selection of low-, intermediate-
and high-resistance phenotypes. Drug resistance was associated with
significant changes in expression of 330 genes, mainly during early
or intermediate stage. Functional annotation revealed a majority
of genes involved in signal transduction, cell adhesion and cytoskeleton
with subsequent alterations in apoptotic response, cell cycle control,
drug transport, fluoropyrimidine metabolism and DNA repair. A set
of 33 genes distinguished all resistant subclones from sensitive
progenitor cells. In the early stage, downregulation of collagens
and keratins, together with upregulation of profilin 2 and ICAM-2,
suggested cytoskeletal changes and cell adhesion remodeling. Interestingly,
6 members of the S100 calcium-binding protein family were suppressed.
Acquisition of the intermediate-resistance phenotype included upregulation
of the well-known drug resistance gene ABCC6 (ATP-binding cassette
subfamily C member 6). The very small number of genes affected during
transition to high resistance included the primary FU target thymidylate
synthase. Although limited to an in vitro model, our data suggest
that resistance to FU cannot be explained by known mechanisms alone
and substantially involves a wide molecular repertoire. This study
emphasizes the understanding of resistance as a time-depending process:
the cell is particularly challenged at the beginning of this process,
while acquisition of the high-resistance phenotype seems to be less
demanding. © 2004 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {colon cancer, 5-fluorouracil, drug resistance, expression profiling,
microarray},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.20401}
}
@ARTICLE{Schmidt2006a,
author = {Schmidt, Wolfgang M. and Sedivy, Roland and Forstner, Birgit and
Steger, Guenther G. and Zoechbauer, Sabine and Mader, Robert M.},
title = {The balance of methylation and demethylation in colorectal cancer},
journal = {AACR Meeting Abstracts},
year = {2006},
volume = {2006},
pages = {761-a--},
number = {1},
month = apr,
abstract = {Epigenetic gene silencing is a prominent feature of many types of
cancer. In colorectal cancer, we investigated the expression of the
DNA methyltransferases 1 (DNMT1), 3A, and 3B (DNMT3A and DNMT3B,
respectively) in comparison with methyl-CpG binding domain protein
2 (MBD2), recently described as the only active DNA demethylase.
A total of 102 fresh tissue specimen (mucosa, aberrant crypt foci
[ACF], adenomas, and malignant tissue) from patients scheduled for
routine surgery was shock frozen before isolation of total RNA. After
quality control, 0.25 {micro}g RNA were subjected to multiplex reverse-transcriptase
PCR with subsequent quantification by capillary electrophoresis (Agilent
Bioanalyzer 2100). Data analysis focused on 96 samples characterized
by a strong MBD2 expression. Legend: Numbers represent integrated
peak areas (mean {+/-} 95% confidence interval) No significant difference
between the sample groups was observed for MBD2. In contrast, the
expression of DNMT1 and DNMT3A increased in parallel to the degree
of dysplasia, with a highly significant overexpression in the malignoma
when compared with adjacent mucosa (Kruskal-Wallis test with Dunn's
multiple comparison test; p < 0.01 for both). This was also true
when calculating statistics based on the ratio between DNA methyltransferases
and MBD2. In comparison to MBD2, the cumulative expression of all
three DNA methyltransferases was significantly higher in the malignoma
(21% of MBD2) when compared with both, mucosa (13%, p < 0.01) and
benign neoplasia (12%, p < 0.05). Taken together, this data suggest
a relevant role of the DNA methyltransferases 1 and 3A during colorectal
tumorigenesis. This increase is not counterbalanced by enhanced expression
of the demethylating component MBD2, which was not differentially
regulated during tumorigenesis. As a consequence, epigenetic regulation
in the adenoma-carcinoma sequence may be driven by increased methylating
activity rather than suppressed demethylation. F1"> WIDTH=200 HEIGHT=46
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url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/761-a}
}
@ARTICLE{Schmidt2007,
author = {Schmidt, Wolfgang M. and Sedivy, Roland and Forstner, Birgit and
Steger, Günther G. and Zöchbauer-Müller, Sabine and Mader, Robert
M.},
title = {Progressive up-regulation of genes encoding DNA methyltransferases
in the colorectal adenoma-carcinoma sequence},
journal = {Mol. Carcinog.},
year = {2007},
volume = {46},
pages = {766--772},
number = {9},
abstract = {Abstract 10.1002/mc.20307.abs Epigenetic silencing is a prominent
feature of cancer. Here, we investigated the expression of DNA demethylase
and three DNA methyltransferases during colorectal tumorigenesis
comparing the genes encoding DNA methyltransferases 1 (DNMT1), 3A,
and 3B (DNMT3A and DNMT3B) with methyl-CpG binding domain protein
2 (MBD2), recently described as the only active DNA demethylase.
Total RNA isolated from normal colonic mucosa (n = 24), benign
adenomas (n = 18), and malignant colorectal carcinomas (n = 32)
was analyzed by reverse transcriptase-PCR with subsequent quantification
by capillary gel electrophoresis. In contrast to MBD2, expression
of DNMT1 and DNMT3A increased in parallel to the degree of dysplasia,
with significant overexpression in the malignant lesion when compared
with mucosa or with benign lesions (DNMT1). Pairwise comparisons
between tumors and matched, adjacent healthy mucosa tissue (n = 13)
revealed that expression of all three genes encoding DNA methyltransferases
increased by two- to three-fold. Our data suggest a relevant role
of the DNA methyltransferases during colorectal tumorigenesis. This
increase is not counterbalanced by enhanced expression of the demethylating
component MBD2. As a consequence, epigenetic regulation in the adenoma-carcinoma
sequence may be driven by increased methylating activity rather than
suppressed demethylation. © 2007 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {colorectal tumorigenesis, epigenetics, demethylase},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20307}
}
@ARTICLE{Schmidt2009a,
author = {Schmidt, Wolfgang M. and Spiel, Alexander O. and Jilma, Bernd and
Wolzt, Michael and Müller, Markus},
title = {In vivo profile of the human leukocyte microRNA response to endotoxemia},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {380},
pages = {437--441},
number = {3},
month = mar,
abstract = {To gain insight into microRNAs (miRNAs) involved in the regulation
of the human innate immune response, we screened for differentially
expressed miRNAs in circulating leukocytes in an in vivo model of
acute inflammation triggered by Escherichia coli lipopolysaccharide
(LPS) infusion. Leukocyte RNA was isolated from venous blood samples
obtained from healthy male volunteers before and 4 h after LPS-infusion.
After fluorescence labeling, RNA samples were hybridized to microarrays
containing capture probes for measuring the abundance of more than
600 human miRNAs. Target genes were predicted for differentially
expressed miRNAs and then compared to changes in genome-wide expression
levels, which had been established in a previous study. Data analysis
revealed that five miRNAs consistently responded to LPS-infusion,
four of which were down-regulated (miR-146b, miR-150, miR-342, and
let-7g) and one was up-regulated (miR-143). The miR-150 and mir-342
response was confirmed by real-time PCR. By correlating to measured
LPS-induced changes of the leukocyte transcriptome, we next searched
for predicted target genes, whose stability might be under (co-)
control by these miRNAs. We found that the rapid transcriptional
activation during acute inflammation of select genes, such as the
gene encoding interleukin-1 receptor-associated kinase 2 (IRAK2)
might be facilitated by decreased levels of LPS-responsive miRNAs.
The increased level of miR-143 might be associated with the pronounced
down-regulation of the B-cell CLL/lymphoma 2 (BCL2) gene expression
during LPS endotoxemia, and could further be involved in the translational
silencing of several other predicted inflammation-related target
genes. This is the first in vivo study to demonstrate relative abundance
of miRNA levels in peripheral blood leukocytes during acute LPS-induced
inflammation. The miRNAs and their potential target genes identified
herein contribute to the understanding of the complex transcriptional
program of innate immunity initiated by pathogens.},
issn = {0006-291X},
keywords = {Lipopolysaccharide, Endotoxemia, Inflammation, MicroRNA, Gene expression
profiling},
url = {http://www.sciencedirect.com/science/article/B6WBK-4VGPN2C-1/2/5cd1cd876f5fb3b401a80227e8167e99}
}
@ARTICLE{Schmidt-Kastner2002,
author = {Schmidt-Kastner, Rainald and Zhang, Baotong and Belayev, Ludmila
and Khoutorova, Larissa and Amin, Rupen and Busto, Raul and Ginsberg,
Myron D.},
title = {DNA microarray analysis of cortical gene expression during early
recirculation after focal brain ischemia in rat},
journal = {Molecular Brain Research},
year = {2002},
volume = {108},
pages = {81--93},
number = {1-2},
month = dec,
abstract = {Focal brain ischemia is followed by changes in gene expression as
reflected by altered mRNA levels. DNA microarray analysis can be
used to survey thousands of genes for differential expression triggered
by ischemic metabolic stress. In this study, Sprague-Dawley rats
were subjected to 2 h of middle cerebral artery occlusion (MCAO)
using an intravascular poly--lysine-coated filament, and brains were
removed after 3 h of recirculation for mRNA isolation. A differential
measurement of mRNAs from post-ischemic and sham control animals
was performed using the Mouse UniGene 1 microarray. Established values
for differential expression were used (>=1.7 or <=-1.7 fold), and
hits (n=2-3 arrays) divided into known [`]ischemia-hypoxia response'
genes and [`]newly connected' annotated genes. n=28 ischemia-hypoxia
response genes were up-regulated and n=6 were down-regulated. Regulated
genes comprised immediate early genes, heat shock proteins, anti-oxidative
enzymes, trophic factors, and genes involved in RNA metabolism, inflammation
and cell signaling. Based on the ability of the microarray to replicate
known changes in gene expression, n=35 newly connected genes were
found up-regulated and n=41 down-regulated. DNA microarray analysis
allows one to develop novel working hypotheses for responses to brain
ischemia based on the regulation of annotated genes.},
issn = {0169-328X},
keywords = {Microarray, Ischemia, Gene expression, mRNA},
url = {http://www.sciencedirect.com/science/article/B6T07-478RS8X-7/2/12750bc8bd5d02c82f352e1c1d6bf55a}
}
@ARTICLE{Schmidt-Ott2005,
author = {Schmidt-Ott, Kai M. and Yang, Jun and Chen, Xia and Wang, Howard
and Paragas, Neal and Mori, Kiyoshi and Li, Jau-Yi and Lu, Benson
and Costantini, Frank and Schiffer, Mario and Bottinger, Erwin and
Barasch, Jonathan},
title = {Novel Regulators of Kidney Development from the Tips of the Ureteric
Bud},
journal = {J. Am. Soc. Nephrol.},
year = {2005},
volume = {16},
pages = {1993--2002},
number = {7},
month = jul,
abstract = {Mammalian nephrogenesis depends on the interaction between the ureteric
bud and the metanephric mesenchyme. As the ureteric bud undergoes
branching and segmentation, the stalks differentiate into the collecting
system of the mature kidney, while the tip cells interact with the
adjacent cells of the metanephric mesenchyme, inducing their conversion
into nephrons. This induction is mediated by secreted factors. For
identifying novel mediators, the tips of the ureteric tree were isolated
and microarray analyses were performed using manually refined, multistep
gene ontology annotations. For identifying conserved factors, two
databases were developed, one from mouse E12.5 and one from rat E13.5
ureteric buds. The overlap of mouse and rat data sets yielded 20
different transcripts that were enriched in the ureteric bud compared
with metanephric mesenchyme and predicted to code for secreted proteins.
Real-time reverse transcriptase-PCR and in situ hybridization confirmed
these identifications. One of the genes that was highly specific
to the ureteric bud tip was cytokine-like factor 1 (CLF-1). Recombinant
CLF-1 in complex with its physiologic ligand, cardiotrophin-like
cytokine (CLC), triggered phosphorylation of signal transducer and
activator of transcription 3 in mesenchyme, a pathway characteristic
of mesenchymal-to-epithelial conversion. Indeed, when applied to
isolated rat metanephric mesenchyme, CLF-1/CLC (3 nM) induced mature
nephron structures expressing glomerular and tubular markers. These
results underline the power of this first comprehensive gene expression
analysis of the ureteric bud tip to identify bioactive molecules.},
url = {http://jasn.asnjournals.org/cgi/content/abstract/16/7/1993}
}
@ARTICLE{Schmieder2010,
author = {Schmieder, Robert and Lim, Yan and Rohwer, Forest and Edwards, Robert},
title = {TagCleaner: Identification and removal of tag sequences from genomic
and metagenomic datasets},
journal = {BMC Bioinformatics},
year = {2010},
volume = {11},
pages = {341},
number = {1},
abstract = {BACKGROUND:Sequencing metagenomes that were pre-amplified with primer-based
methods requires the removal of the additional tag sequences from
the datasets. The sequenced reads can contain deletions or insertions
due to sequencing limitations, and the primer sequence may contain
ambiguous bases. Furthermore, the tag sequence may be unavailable
or incorrectly reported. Because of the potential for downstream
inaccuracies introduced by unwanted sequence contaminations, it is
important to use reliable tools for pre-processing sequence data.RESULTS:TagCleaner
is a web application developed to automatically identify and remove
known or unknown tag sequences allowing insertions and deletions
in the dataset. TagCleaner is designed to filter the trimmed reads
for duplicates, short reads, and reads with high rates of ambiguous
sequences. An additional screening for and splitting of fragment-to-fragment
concatenations that gave rise to artificial concatenated sequences
can increase the quality of the dataset. Users may modify the different
filter parameters according to their own preferences.CONCLUSIONS:TagCleaner
is a publicly available web application that is able to automatically
detect and efficiently remove tag sequences from metagenomic datasets.
It is easily configurable and provides a user-friendly interface.
The interactive web interface facilitates export functionality for
subsequent data processing, and is available at http://edwards.sdsu.edu/tagcleaner.},
doi = {10.1186/1471-2105-11-341},
issn = {1471-2105},
pubmedid = {20573248},
url = {http://www.biomedcentral.com/1471-2105/11/341}
}
@ARTICLE{Schmitz2011,
author = {John C. Schmitz and Petr Protiva and Arijeet K. Gattu and Teruo Utsumi
and Yasuko Iwakiri and Antonio G. Neto and Margo Quinn and Mona L.
Cornwell and Philip Fitchev and Aurelia Lugea and Susan E. Crawford
and Chuhan Chung},
title = {Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic
Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1},
journal = {The American Journal of Pathology},
year = {2011},
volume = {179},
pages = {2990 - 2999},
number = {6},
abstract = {Pigment epithelium-derived factor (PEDF) is important for maintaining
the normal extracellular matrix. We hypothesized that the initiation
of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic
PEDF expression was assessed in wild-type mice fed either a control
or ethanol diet using an intragastric feeding model. Pancreatitis
responses were elicited with either a single episode or a repetitive
cerulein-induced (50 μg/kg, 6 hourly i.p. injections) protocol in
wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting
were performed to assess fibrogenic responses. In wild-type animals,
PEDF expression increased with pancreatitis and was more pronounced
in mice fed ethanol. Compared with wild-type mice, α-smooth muscle
actin staining and expression levels of fibrogenic markers (eg, transforming
growth factor-β1, platelet-derived growth factor, collagen I, and
thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius
red staining revealed more fibrosis in PEDF-null versus wild-type
pancreas 1 week after pancreatitis. Differences in tissue fibrosis
resolved with longer recovery periods. PEDF overexpression suppressed
thrombospondin-1 levels in vitro. Ethanol feeding and experimental
pancreatitis increased PEDF expression in wild-type mice. PEDF-null
mice, however, demonstrated enhanced early fibrotic responses compared
with wild-type mice with pancreatitis. These findings indicate that
PEDF acts as a compensatory antifibrotic cytokine in pancreatitis.},
doi = {10.1016/j.ajpath.2011.08.009},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S000294401100811X}
}
@ARTICLE{Schmitz-Winnenthal2007,
author = {Schmitz-Winnenthal, F.H. and Galindo-Escobedo, L.V. and Rimoldi,
D. and Geng, W. and Romero, P. and Koch, M. and Weitz, J. and Krempien,
R. and Niethammer, A.G. and Beckhove, P. and Buchler, M.W. and Z'graggen,
K.},
title = {Potential target antigens for immunotherapy in human pancreatic cancer},
journal = {Cancer Letters},
year = {2007},
volume = {252},
pages = {290--298},
number = {2},
month = jul,
abstract = {Background To be effective and selective, immunotherapy ideally targets
specifically tumor cells and spares normal tissues. Identification
of tumor specific antigens is a prerequisite to establish an effective
immunotherapy. Still very little is known about the expression of
tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens
(CT) are antigens shared by a variety of malignant tumors, but not
by normal tissues with the exception of germ cells in testis. Restricted
expression in neoplastic tissues and inherent immunogenic features
make CT antigens ideal for use in immunotherapy. We analyzed the
expression of a selected panel of nine CT antigens that have been
proven to elicit an efficient immunogenic response in other malignancies.
In addition we analyzed the expression of HERV-K-MEL, an immunogenic
antigen of viral origin.Methods Pancreatic adenocarcinoma tumor samples
(n = 130) were obtained intraoperatively, control tissues (n = 23)
were collected from cadaveric donor and from patients with chronic
pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3,
MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL
was assessed by PCR. Sequencing of PCR products were performed to
assess the expression of SSX-4 in neoplastic and normal pancreatic
tissues.Results Three of 10 tested antigens were expressed in over
10% of malignant pancreatic tissue samples. SSX-4 was found positive
in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No
expression of CT antigens was found in non-malignant pancreatic tissue
with the exception of SSX-4 and and SSX-2.Conclusions Fifty two percentage
of the analyzed tissues expressed at least one CT antigen. The concomitant
expression of SSX-4 in both malignant and non-malignant pancreatic
tissue is a new finding which may raise concerns for immunotherapy.
However, HERV-K-MEL is expressed with a relatively high prevalence
and may be a candidate for specific immunotherapy in a large subgroup
of pancreatic cancer patients. This study advocates the analysis
of patients with regard to their immunogenic profile before the onset
of antigen-specific immunotherapy.},
issn = {0304-3835},
keywords = {Pancreatic cancer, Tumor associated antigens, Specific immune response,
HERV-K-Mel, Cancer testis antigen},
url = {http://www.sciencedirect.com/science/article/B6T54-4N3X0XB-3/2/bcd22975824076ebff95cffefb2ec83f}
}
@ARTICLE{Schmoker2007,
author = {Schmoker, Joseph D. and McPartland, Kenneth J. and Fellinger, Erika
K. and Boyum, Jon and Trombley, Lucy and Ittleman, Frank P. and Terrien
III, Christopher and Stanley, Andrew and Howard, Alan},
title = {Matrix metalloproteinase and tissue inhibitor expression in atherosclerotic
and nonatherosclerotic thoracic aortic aneurysms},
journal = {The Journal of Thoracic and Cardiovascular Surgery},
year = {2007},
volume = {133},
pages = {155--161},
number = {1},
month = jan,
abstract = {Objectives The altered expression of matrix metalloproteinases and
their inhibitors influences the formation of atherosclerotic abdominal
aortic aneurysms. Their association with thoracic aneurysms is less
clear. This study describes the expression of metalloproteinases
and their inhibitors in atherosclerotic and nonatherosclerotic thoracic
aneurysms, and compares these with age-matched controls.Methods Matrix
metalloproteinase-2 and 9 activity were measured by antibody capture,
and tissue inhibitor-1 and 2 levels were measured by enzyme-linked
immunosorbent assay in 24 patients with atherosclerotic aneurysms
and in 63 patients with nonatherosclerotic aneurysms. Gene expression
was assessed with reverse transcriptase polymerase chain reaction.
The results were compared with 17 controls.Results Data are in nanograms
per milligram of protein. Matrix metalloproteinase-2 activity was
greater in controls than in the atherosclerotic and nonatherosclerotic
groups (80 ± 67 vs 49 ± 50 and 35 ± 44, P = .002). Matrix metalloproteinase-9
activity was greater in the atherosclerotic group than in the nonatherosclerotic
group and controls (11.7 ± 15.7 vs 2.5 ± 2.2 and 1.7 ± 1.9, P = .001).
Tissue inhibitor-1 and 2 levels were greater in controls than in
either aneurysm group (tissue inhibitor of metalloproteinase-1: 376
± 192 vs 234 ± 233 and 174 ± 148, P = .003; tissue inhibitor of metalloproteinase-2:
143 ± 74 vs 14 ± 13 and 27 ± 43, P < .001). Atherosclerotic aneurysms
expressed more matrix metalloproteinase mRNA than controls.Conclusions
The metalloproteinase/tissue inhibitor phenotype of atherosclerotic
thoracic aneurysms is similar to that of abdominal aneurysms. The
diminished expression of metalloproteinases and tissue inhibitors
in nonatherosclerotic thoracic aneurysms relative to aged controls
may represent a loss of smooth muscle cells.},
issn = {0022-5223},
url = {http://www.sciencedirect.com/science/article/B6WMF-4MPC36B-V/2/30548d10a113daf2c5aab0eb8cf196c5}
}
@ARTICLE{Schmuck2011,
author = {Schmuck, Rosa and Warneke, Viktoria and Behrens, Hans-Michael and
Simon, Eva and Weichert, Wilko and Röcken, Christoph},
title = {Genotypic and Phenotypic Characterization of Side Population of Gastric
Cancer Cell Lines},
journal = {The American Journal of Pathology},
year = {2011},
volume = {178},
pages = {1792--1804},
number = {4},
month = apr,
abstract = {The side population (SP) of tumor cell lines shares characteristics
with tumor stem cells. The objective of this study was to phenotypically
and genotypically characterize the SP of gastric cancer cell lines.
SP cells were obtained from AGS and MKN45 gastric cancer cells using
Hoechst 33342 staining and fluorescence-activated cell sorting. The
cells were subsequently studied morphologically at cytology and immunocytochemistry,
on the transcriptional level via gene array, and in cell culture
using recultivation assays. Genes differentially expressed in SP
cells were evaluated at immunohistochemistry in tissue samples from
486 patients with gastric cancer. The SP cells were smaller and rounder
then non-SP cells. SP cells self-renewed in recultivation experiments
and differentiated into SP and non-SP cells. Recultivated SP and
non-SP cells exhibited distinct phenotypes in culture insofar as
cell shape and colony formation. SP cells demonstrated increased
levels of the stem cell markers CD133 and Musashi-1. Transcriptional
analyses demonstrated that SP cells express genes that encode for
stem cell properties including FZD7, HEY1, SMO, and ADAM17. It was
observed that ADAM17 and FZD7 are differentially expressed in human
gastric cancer, and FZD7-positive cancers are associated with significantly
shorter patient survival. In conclusion, human gastric cancer cell
lines enclose a phenotypically and genotypically distinct cell population
with tumor stem cell features. Phenotypic characteristics of this
distinct cell population are also present in gastric cancer tissue,
and correlate with patient survival.},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011000435}
}
@ARTICLE{Schmut2002,
author = {Schmut, O and Horwath-Winter, J and Zenker, A and Trummer, G},
title = {The effect of sample treatment on separation profiles of tear fluid
proteins: qualitative and semi-quantitative protein determination
by an automated analysis system.},
journal = {Graefes Arch Clin Exp Ophthalmol},
year = {2002},
volume = {240},
pages = {900-5},
number = {11},
month = nov,
abstract = {PURPOSE: Qualitative and quantitative determination of tear fluid
components is of increasing interest in ophthalmology. Until now,
for diagnosis and course control of some diseases of the anterior
parts of the eye, different methods for tear fluid protein analysis
are available. Results can be obtained by polyacrylamide gel electrophoresis
(PAGE), immunochemistry, and high-performance liquid chromatography
(HPLC). A new method for protein separation, identification and semi-quantitative
determination on a chip-based micro-fluidic technique is used for
the first time to investigate tear fluids. METHODS: Normal human
reflex tears were obtained by stimulation with China mint oil and
collected using glass capillary tubes. A lab-on-a-chip technology
(developed by Agilent Technologies, Waldbronn, Germany, in co-operation
with Caliper Technologies, Mountain View, California, USA) was used
for separation and semi-quantitative determination of tear proteins.
Tear fluid was separated on the Agilent 2100 Bioanalyzer in combination
with the Protein 200 LabChip kit and the dedicated protein assay
software. Time and temperature of the incubation with sample buffer
were varied, and the influence of these parameters on protein separation
profiles was studied. Tear proteins were also analysed by PAGE, and
the results obtained by both methods were compared. RESULTS: The
different proteins of tear fluid can be separated by the Agilent
2100 Bioanalyzer method in very short time. By this method, the molecular
weight as well as the concentration of proteins can be determined.
Data are automatically stored in digital format and can be retrieved
and shared. Results of this technology were comparable with the protein
pattern obtained by PAGE. It was confirmed by both methods that,
depending on incubation time of tear fluid with sample buffer and
on temperature, different protein pattern can be obtained from the
tears of one specimen. CONCLUSION: Tear proteins - in contrast to
serum or aqueous humour proteins - are very sensitive to changes
in sample buffer temperature as well as incubation time with buffer.
To obtain comparable results for tear fluid proteins, the sample
buffer applied and the incubation time and temperature must be observed
carefully. This can be demonstrated by both the new Agilent 2100
Bioanalyzer method and PAGE. These results are of importance when
comparing tear fluid protein pattern for the diagnosis and course
control of dry-eye syndrome and of other diseases of the anterior
part of the eye.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12486511}
}
@ARTICLE{Schnabolk2010,
author = {Schnabolk, Gloriane W. and Gupta, Bhawna and Mulgaonkar, Aditi and
Kulkarni, Mrugaya and Sweet, Douglas H.},
title = {Organic Anion Transporter 6 (Slc22a20) Specificity and Sertoli Cell-Specific
Expression Provide New Insight on Potential Endogenous Roles},
journal = {J. Pharmacol. Exp. Ther.},
year = {2010},
volume = {334},
pages = {927--935},
number = {3},
month = sep,
abstract = {Organic anion transporter 6 (Oat6; Slc22a20), a member of the OAT
family, was demonstrated previously to mediate the transport of organic
anions (Am J Physiol Renal Physiol 291:F314-F321, 2006). In the present
study, we sought to further delineate the function of murine Oat6
(mOat6) by analyzing the effect of select organic anions on mOat6-mediated
transport by using a Chinese hamster ovary (CHO) cell line stably
expressing mOat6 (CHO-mOat6). When examined, kinetic analysis demonstrated
that the mechanism of inhibition of mOat6 and mOat3 was competitive.
Homovanillic acid, 5-hydroxyindole acetic acid, 2,4-dihydroxyphenylacetate,
hippurate, and dehydroepiandrosterone sulfate (DHEAS) each significantly
reduced mOat6 activity with inhibitory constant (Ki) values of 3.0
{+/-} 0.5, 48.9 {+/-} 10.3, 61.4 {+/-} 7.1, 59.9 {+/-} 4.9, and 38.8
{+/-} 3.1 {micro}M, respectively. Comparison to Ki values determined
for mOat3 (67.8 {+/-} 7.2, 134.5 {+/-} 27.0, 346.7 {+/-} 97.9, 79.3
{+/-} 4.0, and 3.8 {+/-} 1.1 {micro}M, respectively) revealed that
there are significant differences in compound affinity between each
transporter. Fluoroquinolone antimicrobials and reduced folates were
without effect on mOat6-mediated uptake. Investigation of testicular
cell type-specific expression of mOat6 by laser capture microdissection
and quantitative polymerase chain reaction revealed significant mRNA
expression in Sertoli cells, but not in Leydig cells or spermatids.
Overall, these data should aid further refinements to the interpretation
and modeling of the in vivo disposition of OAT substrates. Specifically,
expression in Sertoli cells suggests Oat6 may be an important determinant
of blood-testis barrier function, with Oat6-mediated transport of
estrone sulfate and DHEAS possibly representing a critical step in
the maintenance of testicular steroidogenesis.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/334/3/927}
}
@ARTICLE{Schnackenberg2010,
author = {Schnackenberg, B.J. and Saini, U.T. and Robinson, B.L. and Ali, S.F.
and Patterson, T.A.},
title = {An acute dose of gamma-hydroxybutyric acid alters gene expression
in multiple mouse brain regions},
journal = {Neuroscience},
year = {2010},
volume = {170},
pages = {523--541},
number = {2},
month = oct,
abstract = {Gamma-hydroxybutyric acid (GHB) is normally found in the brain in
low concentrations and may function as a neurotransmitter, although
the mechanism of action has not been completely elucidated. GHB has
been used as a general anesthetic and is currently used to treat
narcolepsy and alcoholism. Recreational use of GHB is primarily as
a "club drug" and a "date rape drug," due to its amnesic effects.
For this study, the hypothesis was that behavioral and neurochemical
alterations may parallel gene expression changes in the brain after
GHB administration. Adult male C57/B6N mice (n=5/group) were administered
a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and
4 h after treatment. Control mice were administered saline. Brains
were removed and regionally dissected on ice. Total RNA from the
hippocampus, cortex and striatum was extracted, amplified and labeled.
Gene expression was evaluated using Agilent whole mouse genome 4×44K
oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack(TM)
and differentially expressed genes (DEGs) were identified using P<=0.01
and a fold change >=1.7 as the criteria for significance. Principal
component analysis (PCA) and Hierarchical Cluster Analysis (HCA)
showed that samples from each time point clustered into distinct
treatment groups with respect to sacrifice time. Ingenuity pathways
analysis (IPA) was used to identify involved pathways. The results
show that GHB induces gene expression alterations in hundreds of
genes in the hippocampus, cortex and striatum, and the number of
affected genes increases throughout a 4-h time course. Many of these
DEGs are involved in neurological disease, apoptosis, and oxidative
stress.},
issn = {0306-4522},
keywords = {microarray, PCR array, oxidative stress, memory, long-term potentiation,
GHB},
url = {http://www.sciencedirect.com/science/article/B6T0F-50K5T37-1/2/4054d5c89b3d4271010075a9f257dd16}
}
@ARTICLE{Schneider2009,
author = {Schneider, Claudia and Schuetz, Gunnar and Zollner, Thomas M.},
title = {Acute neuroinflammation in Lewis rats -- A model for acute multiple
sclerosis relapses},
journal = {Journal of Neuroimmunology},
year = {2009},
volume = {213},
pages = {84--90},
number = {1-2},
month = aug,
abstract = {Animal models of experimental allergic encephalomyelitis (EAE) are
the most commonly used animal models for studying the pathogenesis
of human multiple sclerosis (MS) as well as for target validation
and compound characterization in pharmacology. By using an EAE model
in Lewis rats, we focus on its neuroimmunological characterization
with special attention to disease-involved cytokines, chemokines,
and adhesion molecules. Furthermore, we used MR imaging to investigate
macrophage infiltration and ICAM-1 expression in lesional spinal
cord. Overall, due to its inflammatory character, this model is suggested
to be used in early drug discovery particularly directed against
acute inflammatory processes.},
issn = {0165-5728},
keywords = {Multiple sclerosis, Experimental allergic encephalomyelitis, Inflammation,
ICAM-1, Magnetic resonance imaging},
url = {http://www.sciencedirect.com/science/article/B6T03-4WM689H-1/2/e51eacb24165e175b4e8399c5f348a95}
}
@ARTICLE{Schneider2011,
author = {J.S. Schneider and D.W. Anderson and H. Sonnenahalli and R. Vadigepalli},
title = {Sex-based differences in gene expression in hippocampus following
postnatal lead exposure},
journal = {Toxicology and Applied Pharmacology},
year = {2011},
volume = {256},
pages = {179 - 190},
number = {2},
abstract = {The influence of sex as an effect modifier of childhood lead poisoning
has received little systematic attention. Considering the paucity
of information available concerning the interactive effects of lead
and sex on the brain, the current study examined the interactive
effects of lead and sex on gene expression patterns in the hippocampus,
a structure involved in learning and memory. Male or female rats
were fed either 1500 ppm lead-containing chow or control chow
for 30 days beginning at weaning.Blood lead levels were 26.7 ± 2.1 μg/dl
and 27.1 ± 1.7 μg/dl for females and males, respectively.
The expression of 175 unique genes was differentially regulated between
control male and female rats. A total of 167 unique genes were differentially
expressed in response to lead in either males or females. Lead exposure
had a significant effect without a significant difference between
male and female responses in 77 of these genes. In another set of
71 genes, there were significant differences in male vs. female response.
A third set of 30 genes was differentially expressed in opposite
directions in males vs. females, with the majority of genes expressed
at a lower level in females than in males. Highly differentially
expressed genes in males and females following lead exposure were
associated with diverse biological pathways and functions. These
results show that a brief exposure to lead produced significant changes
in expression of a variety of genes in the hippocampus and that the
response of the brain to a given lead exposure may vary depending
on sex.},
doi = {10.1016/j.taap.2011.08.008},
issn = {0041-008X},
keywords = {Rat},
url = {http://www.sciencedirect.com/science/article/pii/S0041008X11003061}
}
@ARTICLE{Schneider2006,
author = {Schneider, Jörg and Ruschhaupt, Markus and Buneß, Andreas and Asslaber,
Martin and Regitnig, Peter and Zatloukal, Kurt and Schippinger, Walter
and Ploner, Ferdinand and Poustka, Annemarie and Sültmann, Holger},
title = {Identification and meta-analysis of a small gene expression signature
for the diagnosis of estrogen receptor status in invasive ductal
breast cancer},
journal = {Int. J. Cancer},
year = {2006},
volume = {119},
pages = {2974--2979},
number = {12},
abstract = {Abstract 10.1002/ijc.22234.abs In breast cancer, the determination
of estrogen receptor (ER) expression is crucial for the decision
on therapeutic strategies. Current ER expression analysis is based
on immunohistochemical (IHC) staining of ER on formalin fixed tissue
sections. However, low levels of ER expression frequently escape
detection because of varying sensitivities of routine histopathological
laboratories. Moreover, in estimating ER by IHC the receptor protein
only is tested instead of the complex underlying ER pathway, which
reflects its biological activity. To overcome this limitation, we
have used the microarray technology to study 56 samples of invasive
ductal carcinoma. We infer a robust and reliable signature of 10
genes, which is associated with ER expression and presumably therapeutically
relevant biological processes. In a meta-analysis, the signature
was tested on 3 further independent microarray gene expression data
sets, covering different laboratories, array platforms, and clinics.
The classification based on the signature showed a very low misclassification
rate. In summary, the expression of few genes is sufficient to determine
ER status. Future decisions on antiestrogen based therapy in breast
cancer could be based on this signature rather than on immunostaining
alone. © 2006 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {gene expression profiling, breast cancer, molecular diagnosis and
prognosis, estrogen receptor, meta-analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22234}
}
@ARTICLE{Schneider2011a,
author = {Schneider, Katherine T. and van de Mortel, Martijn and Bancroft,
Timothy J. and Braun, Edward and Nettleton, Dan and Nelson, Rex T.
and Frederick, Reid D. and Baum, Thomas J. and Graham, Michelle A.
and Whitham, Steven A.},
title = {Biphasic Gene Expression Changes Elicited by Phakopsora pachyrhizi
in Soybean Correlate with Fungal Penetration and Haustoria Formation},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {355-371},
number = {1},
abstract = {Inoculation of soybean (Glycine max) plants with Phakopsora pachyrhizi,
the causal organism of Asian soybean rust, elicits a biphasic response
characterized by a burst of differential gene expression in the first
12 h. A quiescent period occurs from 24 to 48 h after inoculation,
in which P. pachyrhizi continues to develop but does not elicit strong
host responses, followed by a second phase of intense gene expression.
To correlate soybean responses with P. pachyrhizi growth and development,
we inoculated the soybean cultivar Ankur (accession PI462312), which
carries the Rpp3 resistance gene, with avirulent and virulent isolates
of P. pachyrhizi. The avirulent isolate Hawaii 94-1 elicits hypersensitive
cell death that limits fungal growth on Ankur and results in an incompatible
response, while the virulent isolate Taiwan 80-2 grows extensively,
sporulates profusely, and produces a compatible reaction. Inoculated
leaves were collected over a 288-h time course for microarray analysis
of soybean gene expression and microscopic analysis of P. pachyrhizi
growth and development. The first burst in gene expression correlated
with appressorium formation and penetration of epidermal cells, while
the second burst of gene expression changes followed the onset of
haustoria formation in both compatible and incompatible interactions.
The proliferation of haustoria coincided with the inhibition of P.
pachyrhizi growth in the incompatible interaction or the beginning
of accelerated growth in the compatible interaction. The temporal
relationships between P. pachyrhizi growth and host responses provide
an important context in which to view interacting gene networks that
mediate the outcomes of their interactions.},
doi = {10.1104/pp.111.181149},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/1/355.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/1/355}
}
@ARTICLE{Schnitzler2010,
author = {Schnitzler, Christine E. and Weis, Virginia M.},
title = {Coral larvae exhibit few measurable transcriptional changes during
the onset of coral-dinoflagellate endosymbiosis},
journal = {Marine Genomics},
year = {2010},
volume = {3},
pages = {107--116},
number = {2},
month = jun,
abstract = {The cellular mechanisms controlling the successful establishment of
a stable mutualism between cnidarians and their dinoflagellate partners
are largely unknown. The planula larva of the solitary Hawaiian scleractinian
coral Fungia scutaria and its dinoflagellate symbiont Symbiodinium
sp. type C1f represents an ideal model for studying the onset of
cnidarian-dinoflagellate endosymbiosis due to the predictable availability
of gametes, the ability to raise non-symbiotic larvae and establish
the symbiosis experimentally, and the ability to precisely quantify
infection success. The goal of this study was to identify genes differentially
expressed in F. scutaria larvae during the initiation of endosymbiosis
with Symbiodinium sp. C1f. Newly symbiotic larvae were compared to
non-symbiotic larvae using a custom cDNA microarray. The 5184-feature
array was constructed with cDNA libraries from newly symbiotic and
non-symbiotic F. scutaria larvae, including 3072 features (60%) that
were enriched for either state by subtractive hybridization. Our
analyses revealed very few changes in the F. scutaria transcriptome
as a result of infection with Symbiodinium sp. C1f, similar to other
studies focused on the early stages of this symbiotic interaction.
We suggest that these results may be due, in part, to an inability
to detect the transcriptional signal from the small percentage of
infected cells compared to uninfected cells. We discuss several other
potential explanations for this result, including suggesting that
certain types of Symbiodinium sp. may have evolved mechanisms to
suppress or circumvent cnidarian host responses to infection.},
issn = {1874-7787},
keywords = {Coral-dinoflagellate endosymbiosis, Coral larvae, Fungia, Microarray,
Symbiodinium, Transcriptome},
url = {http://www.sciencedirect.com/science/article/B8JG7-511GB9Y-1/2/367b27971e7978cddf56147e82042c38}
}
@ARTICLE{Schober2011,
author = {Schober, Markus and Fuchs, Elaine},
title = {Tumor-initiating stem cells of squamous cell carcinomas and their
control by TGF-{beta} and integrin/focal adhesion kinase (FAK) signaling},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {10544-10549},
number = {26},
abstract = {Cancer stem cells (CSCs) sustain tumor growth through their ability
to self-renew and to generate differentiated progeny. These functions
endow CSCs with the potential to initiate secondary tumors bearing
characteristics similar to those of the parent. Recently the hair
follicle stem cell marker CD34 was used to purify a CSC-like cell
population from early skin tumors arising from treatment with 7,12-dimethylbenz[]anthracene/12-o-tetradecanoylphorbol-13-acetate,
which typically generates benign papillomas that occasionally progress
to squamous cell carcinomas (SCCs). In the present study, we identify
and characterize CSCs purified from malignant SCCs. We show that
SCCs contain two highly tumorigenic CSC populations that differ in
CD34 levels but are enriched for integrins and coexist at the SCC-stroma
interface. Intriguingly, whether CD34lo or CD34hi, 6hi{beta}1hi populations
can initiate secondary tumors by serial limit-dilution transplantation
assays, but 6lo{beta}1lo populations cannot. Moreover, secondary
tumors generated from a single CSC of either subtype contain both
CD34lo and CD34hi 6hi{beta}1hiCSCs, indicating their nonhierarchical
organization. Genomic profiling and hierarchical cluster analysis
show that these two CSC subtypes share a molecular signature distinct
from either the CD34- epidermal or the CD34hi hair follicle stem
cell signature. Although closely related, 6hi{beta}1hiCD34lo and
6hi{beta}1hiCD34hi CSCs differ in cell-cycle gene expression and
proliferation characteristics. Indeed, proliferation and expansion
of 6hi{beta}1hiCD34hi CSCs is sensitive to whether they can initiate
a TGF-{beta} receptor II-mediated response to counterbalance elevated
focal adhesion kinase-mediated integrin signaling within the tumor.
Overall, the coexistence and interconvertibility of CSCs with differing
sensitivities to their microenvironment pose challenges and opportunities
for SCC cancer therapies.},
doi = {10.1073/pnas.1107807108},
eprint = {http://www.pnas.org/cgi/reprint/108/26/10544.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/26/10544}
}
@ARTICLE{Schobesberger2008,
author = {Schobesberger, Martina and Baltzer, Anna and Oberli, Andrea and Kappeler,
Andreas and Gugger, Mathias and Burger, Hana and Jaggi, Rolf},
title = {Gene expression variation between distinct areas of breast cancer
measured from paraffin-embedded tissue cores},
journal = {BMC Cancer},
year = {2008},
volume = {8},
pages = {343},
number = {1},
abstract = {BACKGROUND:Diagnosis and prognosis in breast cancer are mainly based
on histology and immunohistochemistry of formalin-fixed, paraffin-embedded
(FFPE) material. Recently, gene expression analysis was shown to
elucidate the biological variance between tumors and molecular markers
were identified that led to new classification systems that provided
better prognostic and predictive parameters. Archived FFPE samples
represent an ideal source of tissue for translational research, as
millions of tissue blocks exist from routine diagnostics and from
clinical studies. These should be exploited to provide clinicians
with more accurate prognostic and predictive information. Unfortunately,
RNA derived from FFPE material is partially degraded and chemically
modified and reliable gene expression measurement has only become
successful after implementing novel and optimized procedures for
RNA isolation, demodification and detection.METHODS:In this study
we used tissue cylinders as known from the construction of tissue
microarrays. RNA was isolated with a robust protocol recently developed
for RNA derived from FFPE material. Gene expression was measured
by quantitative reverse transcription PCR.RESULTS:Sixteen tissue
blocks from 7 patients diagnosed with multiple histological subtypes
of breast cancer were available for this study. After verification
of appropriate localization, sufficient RNA yield and quality, 30
tissue cores were available for gene expression measurement on TaqMan®
Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal
carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores
were lost. Gene expression values were used to calculate scores representing
the proliferation status (PRO), the estrogen receptor status and
the HER2 status. The PRO scores measured from entire sections were
similar to PRO scores determined from IDC tissue cores. Scores determined
from normal tissue cores consistently revealed lower PRO scores than
cores derived from IDC or DCIS of the same block or from different
blocks of the same patient.CONCLUSION:We have developed optimized
protocols for RNA isolation from histologically distinct areas. RNA
prepared from FFPE tissue cores is suitable for gene expression measurement
by quantitative PCR. Distinct molecular scores could be determined
from different cores of the same tumor specimen.},
doi = {10.1186/1471-2407-8-343},
issn = {1471-2407},
pubmedid = {19032762},
url = {http://www.biomedcentral.com/1471-2407/8/343}
}
@ARTICLE{Schoeftner2009,
author = {Schoeftner, Stefan and Blanco, Raquel and de Silanes, Isabel Lopez
and Munoz, Purificacion and Gomez-Lopez, Gonzalo and Flores, Juana
M. and Blasco, Maria A.},
title = {Telomere shortening relaxes X chromosome inactivation and forces
global transcriptome alterations},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {19393--19398},
number = {46},
month = nov,
abstract = {Telomeres are heterochromatic structures at chromosome ends essential
for chromosomal stability. Telomere shortening and the accumulation
of dysfunctional telomeres are associated with organismal aging.
Using telomerase-deficient TRF2-overexpressing mice (K5TRF2/Terc-/-)
as a model for accelerated aging, we show that telomere shortening
is paralleled by a gradual deregulation of the mammalian transcriptome
leading to cumulative changes in a defined set of genes, including
up-regulation of the mTOR and Akt survival pathways and down-regulation
of cell cycle and DNA repair pathways. Increased DNA damage from
dysfunctional telomeres leads to reduced deposition of H3K27me3 onto
the inactive X chromosome (Xi), impaired association of the Xi with
telomeric transcript accumulations (Tacs), and reactivation of an
X chromosome-linked K5TRF2 transgene that is subjected to X-chromosome
inactivation in female mice with sufficiently long telomeres. Exogenously
induced DNA damage also disrupts Xi-Tacs, suggesting DNA damage at
the origin of these alterations. Collectively, these findings suggest
that critically short telomeres activate a persistent DNA damage
response that alters gene expression programs in a nonstochastic
manner toward cell cycle arrest and activation of survival pathways,
as well as impacts the maintenance of epigenetic memory and nuclear
organization, thereby contributing to organismal aging.},
url = {http://www.pnas.org/cgi/content/abstract/106/46/19393}
}
@ARTICLE{Schoenberg2011b,
author = {K.M. Schoenberg and T.R. Overton},
title = {Effects of plane of nutrition and 2,4-thiazolidinedione on insulin
responses and adipose tissue gene expression in dairy cattle during
late gestation},
journal = {Journal of Dairy Science},
year = {2011},
volume = {94},
pages = {6021 - 6035},
number = {12},
abstract = {Specific mechanisms by which dry period dietary energy affects transition
cow metabolism have been intensively investigated but those of thiazolidinedione
(TZD) administration have not. We hypothesized that effects of both
are mediated via changes in insulin, glucose, or fatty acid metabolism.
The objective of this experiment was to determine the effects of
the insulin-sensitizing agent TZD and dietary energy level on glucose
and fatty acid metabolism during late gestation in dairy cows. Multiparous
Holstein cows (n = 32) approximately 50 d before expected
calving date were dried-off and assigned to 1 of 2 dietary energy
levels for 3 wk (high: 1.52 Mcal/kg of NEL, or low: 1.34 Mcal/kg
of NEL) and treated daily during the final 14 d with 4.0 mg
of TZD/kg of body weight (BW) or saline in a completely randomized
design. Cows fed the low energy diet had lower dry matter intake
(12.8 vs. 16.1 kg/d) and higher plasma nonesterified fatty acid
(NEFA) concentrations (103.3 vs. 82.4 μEq/L) compared with
cows fed the high energy diet. Cows administered TZD had higher plasma
glucose concentrations (62.5 vs. 59.6 mg/dL) than saline controls
and cows fed the high energy diet had higher plasma insulin concentrations
(35.1 vs. 25.3 μU/mL) compared with those fed the low energy
diet. After 2 wk of TZD treatment, all cows were subjected to an
intravenous glucose tolerance test (GTT; 0.25 g of dextrose/kg
of BW) followed 110 min later by an insulin challenge (IC; 1.0 μg
of insulin/kg of BW). Differences in plasma glucose response to GTT
were minimal based on diet; however, cows fed the low energy diet
had more negative NEFA areas under the curve (AUC; −4,838 vs. −2,137 μEq/L
× min over 90 min) and greater rates of NEFA decrease (1.35
vs. 0.63%/min) during GTT, suggesting differential responses of tissue
glucose and fatty acid metabolism in response to dietary energy level.
During IC, the TZD-treated cows tended to have more negative glucose
AUC (−45.0 vs. −12.1 mg/dL × min over 15 min) than
controls, suggesting that TZD-treated cows had greater responses
to insulin. Limited interactions were observed between dietary and
TZD treatments in all response variables measured. Adipose tissue
biopsies performed on the final day of treatment suggested higher
expression of peroxisome proliferator-activated receptor-γ (0.71
vs. 0.50 relative expression) and lipoprotein lipase (0.71 vs. 0.40
relative expression) in cows fed the high energy diet as measured
by quantitative real-time PCR. These results indicate that energy
level and insulin-sensitizing agents affect glucose and lipid metabolism
during the dry period.},
doi = {10.3168/jds.2011-4533},
issn = {0022-0302},
keywords = {thiazolidinedione},
url = {http://www.sciencedirect.com/science/article/pii/S0022030211006357}
}
@ARTICLE{Schoenberg2011a,
author = {K.M. Schoenberg and K.L. Perfield and J.K. Farney and B.J. Bradford
and Y.R. Boisclair and T.R. Overton},
title = {Effects of prepartum 2,4-thiazolidinedione on insulin sensitivity,
plasma concentrations of tumor necrosis factor-α and leptin, and
adipose tissue gene expression},
journal = {Journal of Dairy Science},
year = {2011},
volume = {94},
pages = {5523 - 5532},
number = {11},
abstract = {Administration of peroxisome proliferator-activated receptor gamma
(PPARγ) ligands, thiazolidinediones (TZD), to prepartum dairy cattle
has been shown to improve dry matter intake and decrease circulating
nonesterified fatty acids (NEFA) around the time of calving. The
objective of this work was to elucidate mechanisms of TZD action
in transition dairy cattle by investigating changes in plasma leptin,
tumor necrosis factor-α (TNFα), the revised quantitative insulin
sensitivity check index (RQUICKI), and adipose tissue gene expression
of leptin, PPARγ, lipoprotein lipase (LPL), and fatty acid synthase
(FAS). Multiparous Holstein cows (n = 40) were administered
0, 2.0, or 4.0 mg of TZD/kg of body weight (BW) by intrajugular
infusion once daily from 21 d before expected parturition until
parturition. Plasma samples collected daily from 22 d before
expected parturition through 21 d postpartum were analyzed for
glucose, NEFA, and insulin. Plasma samples collected on d −14,
−3, −1, 1, 3, 7, 14, and 49 relative to parturition were also
analyzed for leptin and TNFα. Adipose tissue was collected on d
7 before expected parturition from a subset of cows, and gene expression
was examined via quantitative real-time PCR. A tendency for a treatment
by time effect on plasma leptin prepartum was observed such that
values were similar on d −14 but cows receiving 2.0 mg/kg
of BW of TZD tended to have lower circulating leptin as calving approached.
Postpartum leptin tended to be increased linearly (2.3, 2.4, and
2.5 ± 0.1 ng/mL for 0, 2.0, and 4.0 mg/kg treatments,
respectively) in cows that received TZD prepartum. Plasma TNFα increased
linearly (2.6, 3.7, and 4.0 ± 0.1 pg/mL) in response to
TZD treatment and decreased through the first week postpartum. Calculation
of RQUICKI 1/[log(glucose) + log(insulin) + log(NEFA)]
suggested altered insulin sensitivity in cows administered TZD that
may depend on day relative to calving. Administration of TZD increased
adipose tissue expression of PPARγ mRNA (11.0, 13.3, and 12.8 ± 1.9).
Administration of TZD had a quadratic effect on gene expression of
leptin (16.2, 10.7, and 17.4 ± 1.6) and no effect on LPL
expression, and expression of FAS was lower for TZD-treated cows
than for controls (8.2, 4.2, and 6.1 ± 1.8, respectively).
Results imply altered expression and plasma concentrations of leptin,
increased plasma TNFα concentrations, and increased expression of
PPARγ in adipose tissue as potential mechanisms for the effects
of TZD administration on transition dairy cattle.},
doi = {10.3168/jds.2011-4501},
issn = {0022-0302},
keywords = {transition period},
url = {http://www.sciencedirect.com/science/article/pii/S0022030211005790}
}
@ARTICLE{Schoenberg2011,
author = {Schoenberg, Katie M. and Giesy, Sarah L. and Harvatine, Kevin J.
and Waldron, Matthew R. and Cheng, Christine and Kharitonenkov, Alexei
and Boisclair, Yves R.},
title = {Plasma FGF21 Is Elevated by the Intense Lipid Mobilization of Lactation},
journal = {Endocrinology},
year = {2011},
volume = {152},
pages = {4652-4661},
number = {12},
abstract = {In many mammals, lactation success depends on substantial use of lipid
reserves and requires integrated metabolic activities between white
adipose tissue (WAT) and liver. Mechanisms responsible for this integration
in lactation are poorly understood, but data collected in other conditions
of elevated lipid use suggest a role for fibroblast growth factor-21
(FGF21). To address this possibility in the context of lactation,
we studied high-yielding dairy cows during the transition from late
pregnancy (LP) to early lactation (EL). Plasma FGF21 was nearly undetectable
in LP, peaked on the day of parturition, and then stabilized at lower,
chronically elevated concentrations during the energy deficit of
EL. Plasma FGF21 was similarly increased in the absence of parturition
when an energy-deficit state was induced by feed restricting late-lactating
dairy cows, implicating energy insufficiency as a cause of chronically
elevated FGF21 in EL. Gene expression studies showed that liver was
a major source of plasma FGF21 in EL with little or no contribution
by WAT, skeletal muscle, and mammary gland. Meaningful expression
of the FGF21 coreceptor {beta}-Klotho was restricted to liver and
WAT in a survey of 15 tissues that included the mammary gland. Expression
of {beta}-Klotho and its subset of interacting FGF receptors was
modestly affected by the transition from LP to EL in liver but not
in WAT. Overall, these data suggest a model whereby liver-derived
FGF21 regulates the use of lipid reserves during lactation via focal
actions on liver and WAT.},
doi = {10.1210/en.2011-1425},
eprint = {http://endo.endojournals.org/cgi/reprint/152/12/4652.pdf},
url = {http://endo.endojournals.org/cgi/content/abstract/152/12/4652}
}
@ARTICLE{Schoggins2011,
author = {Schoggins, John W. and Wilson, Sam J. and Panis, Maryline and Murphy,
Mary Y. and Jones, Christopher T. and Bieniasz, Paul and Rice, Charles
M.},
title = {A diverse range of gene products are effectors of the type I interferon
antiviral response},
journal = {Nature},
year = {2011},
volume = {472},
pages = {481--485},
number = {7344},
month = apr,
comment = {10.1038/nature09907},
issn = {0028-0836},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nature09907}
}
@ARTICLE{Schokker2009,
author = {Schokker, Dirkjan and Hoekman, Arjan J.W. and Smits, Mari A. and
Rebel, Johanna M.J.},
title = {Gene expression patterns associated with chicken jejunal development},
journal = {Developmental \& Comparative Immunology},
year = {2009},
volume = {33},
pages = {1156--1164},
number = {11},
month = nov,
abstract = {Jejunal development occurs in a spatio-temporal pattern and is characterized
by morphological and functional changes. To investigate jejunal development
at the transcriptomic level, we performed microarray studies in 1-21-day-old
chickens. Nine gene clusters were identified, each with a specific
gene expression pattern. Subsequently, groups of genes with similar
functions could be identified. Genes involved in morphological and
functional development were highly expressed immediately after hatch
with declining expression patterns afterwards. Immunological development
can be roughly divided based on expression patterns into three processes
over time; first innate response and immigration of immune cells,
secondly differentiation and specialization, and thirdly maturation
and immune regulation. We conclude that specific gene expression
patterns coincide with the immunological, morphological, and functional
development as measured by other methods. Our data show that transcriptomic
approaches provide more detailed information on the biological processes
underlying jejunal development.},
issn = {0145-305X},
keywords = {Microarray, Time-series, DAVID analysis, Immune system, Jejunum},
url = {http://www.sciencedirect.com/science/article/B6T5X-4WM02X2-1/2/946fe296fe8805a53b61c5a46c8051e8}
}
@ARTICLE{Schokker2010,
author = {Schokker, Dirkjan and Smits, Mari A. and Hoekman, Arjan J.W. and
Parmentier, Henk K. and Rebel, Johanna M.J.},
title = {Effects of Salmonella on spatial-temporal processes of jejunal development
in chickens},
journal = {Developmental \& Comparative Immunology},
year = {2010},
volume = {34},
pages = {1090--1100},
number = {10},
month = oct,
abstract = {To study effects of Salmonella enteritidis on morphological and functional
changes in chicken jejunal development, we analysed gene expression
profiles at seven points post-infection in 1-21 day-old broiler chickens.
Nine clusters with different gene expression patterns were identified,
and the genes in each cluster were further analyzed by a functional
annotation clustering method (DAVID). Functional and morphological
developmental processes dominated in all the nine clusters. Salmonella
infection caused delays in several intestinal-morphological processes,
whereas functional metabolic processes occurred in a similar spatial-temporal
frame compared to normal jejunum development. A clear difference
between normal developing- and Salmonella disturbed jejunum was the
higher expression of genes involved in cell turn-over at early stages
in the infected jejunum. Surprisingly, we found no clustered immune
related processes in the infected birds. To compare the immunological
processes between control and Salmonella infected chickens, the gene
expression data was superimposed on known immunological KEGG pathways.
Furthermore an in-depth analysis on the immune gene level was performed.
As expected, we did find immunological processes in the Salmonella
infected jejunum. Several of these processes could be verified by
immunohistochemistry measurements of different immunological cell
types. However, the well-ordered spatial-temporal development of
the immune system, as observed in control non-infected animals, was
completely abolished in the infected animals. Several immunological
processes started much earlier in time, whereas other processes are
disorganised. These data indicate that normal morphological and immunological
development of jejunum is changed dramatically by a disturbance due
to Salmonella infection. Due to the disturbance, the well-organized
spatial-temporal development of morphological processes are delayed,
those of the immunological development are scattered, whereas metabolic
functional processes are almost not affected. This demonstrates the
flexibility of developmental processes in the broiler chicken intestine.},
issn = {0145-305X},
keywords = {Microarray, Time-series, Intestinal development, DAVID analysis, KEGG
analysis},
url = {http://www.sciencedirect.com/science/article/B6T5X-50B3R03-1/2/4cd0e05eda6d1286a853bd32424c155d}
}
@ARTICLE{Schollaert2004,
author = {Schollaert, Kaila L. and Poisson, Julie M. and Searle, Jennifer S.
and Schwanekamp, Jennifer A. and Tomlinson, Craig R. and Sanchez,
Yolanda},
title = {A Role for Saccharomyces cerevisiae Chk1p in the Response to Replication
Blocks},
journal = {Mol. Biol. Cell},
year = {2004},
volume = {15},
pages = {4051--4063},
number = {9},
month = sep,
abstract = {Replication blocks and DNA damage incurred during S phase activate
the S-phase and intra-S-phase checkpoint responses, respectively,
regulated by the Atrp and Chk1p checkpoint kinases in metazoans.
In Saccharomyces cerevisiae, these checkpoints are regulated by the
Atrp homologue Mec1p and the kinase Rad53p. A conserved role of these
checkpoints is to block mitotic progression until DNA replication
and repair are completed. In S. cerevisiae, these checkpoints include
a transcriptional response regulated by the kinase Dun1p; however,
dun1{Delta} cells are proficient for the S-phase-checkpoint-induced
anaphase block. Yeast Chk1p kinase regulates the metaphase-to-anaphase
transition in the DNA-damage checkpoint pathway via securin (Pds1p)
phosphorylation. However, like Dun1p, yeast Chk1p is not required
for the S-phase-checkpoint-induced anaphase block. Here we report
that Chk1p has a role in the intra-S-phase checkpoint activated when
yeast cells replicate their DNA in the presence of low concentrations
of hydroxyurea (HU). Chk1p was modified and Pds1p was transiently
phosphorylated in this response. Cells lacking Dun1p were dependent
on Chk1p for survival in HU, and chk1{Delta} dun1{Delta} cells were
defective in the recovery from replication interference caused by
transient HU exposure. These studies establish a relationship between
the S-phase and DNA-damage checkpoint pathways in S. cerevisiae and
suggest that at least in some genetic backgrounds, the Chk1p/securin
pathway is required for the recovery from stalled or collapsed replication
forks.},
url = {http://www.molbiolcell.org/cgi/content/abstract/15/9/4051}
}
@ARTICLE{Scholle2008,
author = {Scholle, Michael D. and Banach, Bridget S. and Hamdan, Samir M. and
Richardson, Charles C. and Kay, Brian K.},
title = {Peptide ligands specific to the oxidized form of Escherichia coli
thioredoxin},
journal = {Biochimica et Biophysica Acta (BBA) - Proteins \& Proteomics},
year = {2008},
volume = {1784},
pages = {1735--1741},
number = {11},
month = nov,
abstract = {Thioredoxin (Trx) is a highly conserved redox protein involved in
several essential cellular processes. In this study, our goal was
to isolate peptide ligands to Escherichia coli Trx that mimic protein-protein
interactions, specifically the T7 polymerase-Trx interaction. To
do this, we subjected Trx to affinity selection against a panel of
linear and cysteine-constrained peptides using M13 phage display.
A novel cyclized conserved peptide sequence, with a motif of C(D/N/S/T/G)D(S/T)-hydrophobic-C-X-hydrophobic-P,
was isolated to Trx. These peptides bound specifically to the E.
coli Trx when compared to the human and spirulina homologs. An alanine
substitution of the active site cysteines (CGPC) resulted in a significant
loss of peptide binding affinity to the Cys-32 mutant. The peptides
were also characterized in the context of Trx's role as a processivity
factor of the T7 DNA polymerase (gp5). As the interaction between
gp5 and Trx normally takes place under reducing conditions, which
might interfere with the conformation of the disulfide-bridged peptides,
we made use of a 22 residue deletion mutant of gp5 in the thioredoxin
binding domain (gp5[Delta]22) that bypassed the requirements of reducing
conditions to interact with Trx. A competition study revealed that
the peptide selectively inhibits the interaction of gp5[Delta]22
with Trx, under oxidizing conditions, with an IC50 of ~ 10 [mu]M.},
issn = {1570-9639},
keywords = {Phage display, Peptide, Thioredoxin, T7 DNA polymerase},
url = {http://www.sciencedirect.com/science/article/B73DJ-4SYJS80-2/2/74534028a940340d46518c383f1e5875}
}
@ARTICLE{Scholle2004,
author = {Scholle, Michael D. and Collart, Frank R. and Kay, Brian K.},
title = {In vivo biotinylated proteins as targets for phage-display selection
experiments},
journal = {Protein Expression and Purification},
year = {2004},
volume = {37},
pages = {243--252},
number = {1},
month = sep,
abstract = {Screening phage-displayed combinatorial libraries represents an attractive
method for identifying affinity reagents to target proteins. Two
critical components of a successful selection experiment are having
a pure target protein and its immobilization in a native conformation.
To achieve both of these requirements in a single step, we have devised
cytoplasmic expression vectors for expression of proteins that are
tagged at the amino- or carboxy-terminus (pMCSG16 and 15) via the
AviTag, which is biotinylated in vivo with concurrent expression
of the BirA biotin ligase. To facilitate implementation in high-throughput
applications, the engineered vectors, pMCSG15 and pMCSG16, also contain
a ligase-independent cloning site (LIC), which permits up to 100%
cloning efficiency. The expressed protein can be purified from bacterial
cell lysates with immobilized metal affinity chromatography or streptavidin-coated
magnetic beads, and the beads used directly to select phage from
combinatorial libraries. From selections using the N-terminally biotinylated
version of one target protein, a peptide ligand (Kd=9 [mu]M) was
recovered that bound in a format-dependent manner. To demonstrate
the utility of pMCSG16, a set of 192 open reading frames were cloned,
and protein was expressed and immobilized for use in high-throughput
selections of phage-display libraries.},
issn = {1046-5928},
keywords = {Affinity selection, AviTag, biotinylated proteins, Combinatorial peptides,
Ligation-independent cloning, Target preparation},
url = {http://www.sciencedirect.com/science/article/B6WPJ-4CS4M68-1/2/7e36c43c6886c5b419f742c164d8bc64}
}
@ARTICLE{Schon2008,
author = {Schon, Margarete and Wienrich, B. Gregor and Kneitz, Susanne and
Sennefelder, Helga and Amschler, Katharina and Vohringer, Verena
and Weber, Olaf and Stiewe, Thorsten and Ziegelbauer, Karl and Schon,
Michael P.},
title = {KINK-1, a Novel Small-Molecule Inhibitor of IKK{beta}, and the Susceptibility
of Melanoma Cells to Antitumoral Treatment},
journal = {J Natl Cancer Inst},
year = {2008},
volume = {100},
pages = {862--875},
number = {12},
month = jun,
abstract = {BackgroundIncreasing the efficacy of chemotherapeutics by reducing
chemoresistance may be a useful strategy in cancer therapy. Constitutive
activation of nuclear factor-kappa B (NF-{kappa}B) is a hallmark
of various cancers, including melanoma, which is almost universally
resistant to chemotherapy. NF-{kappa}B is regulated by inhibitory
{kappa}B (I{kappa}B) proteins, which are in turn phosphorylated by
the I{kappa}B kinase (IKK) complex. MethodsThe effect on NF-{kappa}B
activity of a novel small-molecule inhibitor of the {beta} subunit
of IKK (KINK-1; kinase inhibitor of nuclear factor-{kappa}B-1) was
assessed by measuring phosphorylation of the {alpha} subunit of I{kappa}B
by immunoblotting, DNA binding by electrophoretic mobility shift
assays, and nuclear translocation of NF-{kappa}B using immunofluorescence.
Regulation of NF-{kappa}B-dependent gene expression was determined
by microarray analysis, real-time and semiquantitative reverse transcription
polymerase chain reaction (RT-PCR), and Western blot analyses. The
effects of KINK-1 (alone and in combination with cytostatic agents)
on melanoma cells were characterized by assessing proliferation,
soft agar colony formation, and markers of apoptosis. The antitumoral
efficacy of KINK-1 in combination with the cytostatic agents doxorubicin
or camptothecin (all injected intraperitoneally) was tested in vivo
by measuring lung weight and counting metastases in C57BL6 mice (groups
of six) bearing metastases of melanoma cells. All statistical tests
were two-sided. ResultsKINK-1 strongly suppressed both constitutive
and induced NF-{kappa}B activity in melanoma cells. It reduced the
expression of NF-{kappa}B-dependent gene products that regulate proliferation,
cytokine production, and antiapoptotic responses but exhibited little
antiproliferative or proapoptotic activity at the cellular level.
However, KINK-1 markedly increased the activities of some cytostatic
agents in vitro and abrogated doxorubicin-induced NF-{kappa}B activation.
Combined treatment of C57BL6 mice that had been injected with melanoma
cells with KINK-1 and doxorubicin or camptothecin reduced metastases
and pulmonary tumor mass compared with either treatment alone (mean
lung weight 19 days after injection of melanoma cells of mice treated
with 3 mg/kg KINK-1 alone, 1 mg/kg doxorubicin alone, and 1 mg/kg
doxorubicin plus 3 mg/kg KINK-1 = 260 mg, 95% confidence interval
(CI) = 216 to 305 mg; 268 mg, 95% CI = 224 to 313 mg; and 181 mg,
95% CI = 171 to 192 mg, respectively, P < .001 from t tests comparing
mean lung weight of double-treated mice to that in mice treated with
either compound alone). ConclusionInhibition of constitutive and
induced IKK{beta}-activity through treatment with KINK-1 might increase
tumor susceptibility to chemotherapy.},
url = {http://jnci.oxfordjournals.org/cgi/content/abstract/100/12/862}
}
@ARTICLE{Schonbeck2002,
author = {Schonbeck, Uwe and Gerdes, Norbert and Varo, Nerea and Reynolds,
Rebecca S. and Horton, Daniel B. and Bavendiek, Udo and Robbie, Linda
and Ganz, Peter and Kinlay, Scott and Libby, Peter},
title = {Oxidized Low-Density Lipoprotein Augments and 3-Hydroxy-3-Methylglutaryl
Coenzyme A Reductase Inhibitors Limit CD40 and CD40L Expression in
Human Vascular Cells},
journal = {Circulation},
year = {2002},
volume = {106},
pages = {2888--2893},
number = {23},
month = dec,
abstract = {Background-- Although CD40 signaling participates in atherosclerosis,
links between lipid risk factors and this inflammatory pathway remain
obscure. Cardiovascular risk reduction by 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors (statins) may involve actions beyond
lipid lowering, including reduced inflammation. Therefore, this study
analyzed whether oxidized low-density lipoprotein (oxLDL) induces
CD40/CD40L expression on cells implicated in atherogenesis and whether
statins affect their expression in vitro as well as the expression
of soluble CD40L (sCD40L) in vivo. Methods and Results-- Treatment
of human vascular endothelial and smooth muscle cells and mononuclear
phagocytes with oxLDL augmented the basal expression of CD40 and
CD40L mRNA and protein. In contrast, cerivastatin, atorvastatin,
or simvastatin concentration-dependently diminished the constitutive
as well as oxLDL- or cytokine-induced expression of the receptor/ligand
dyad, an effect reversed by mevalonate. Patients treated with statins
had diminished sCD40L plasma levels compared with untreated control
patients (8.3{+/-}3.1 ng/mL [n=11] versus 13.1{+/-}2.5 ng/mL [n=16],
P<0.05), supporting the clinical relevance of the in vitro observations.
Platelet-enriched plasma of mice deficient in CD40L showed markedly
delayed fibrin clot formation, suggesting a role for the ligand in
blood coagulation and supporting the hypothesis that statin-mediated
reduction in CD40/CD40L expression might limit thrombosis. Conclusions--
OxLDL may promote expression of CD40 and CD40L in human atheroma.
Statins may limit the expression of the CD40 receptor/ligand dyad
in two ways, directly as well as through diminished lipoprotein levels.
Thus, reduced CD40 signaling may account for some of the statins'
antiinflammatory action.},
url = {http://circ.ahajournals.org/cgi/content/abstract/106/23/2888}
}
@ARTICLE{Schook2011,
author = {Schook, Paul O. P. and Stohl, Elizabeth A. and Criss, Alison K. and
Seifert, H. Steven},
title = {The DNA-binding activity of the Neisseria gonorrhoeae LexA orthologue
NG1427 is modulated by oxidation},
journal = {Molecular Microbiology},
year = {2011},
volume = {79},
pages = {846--860},
number = {4},
abstract = {Summary Neisseria gonorrhoeae is a human-specific organism that is
not usually exposed to UV light or chemicals but is likely to encounter
reactive oxygen species during infection. Exposure of N. gonorrhoeae
to sublethal hydrogen peroxide revealed that the ng1427 gene was
upregulated sixfold. N. gonorrhoeae was thought to lack an SOS system,
although NG1427 shows amino acid sequence similarity to the SOS response
regulator LexA from Escherichia coli. Similar to LexA and other S24
peptidases, NG1427 undergoes autoproteolysis in vitro, which is facilitated
by either the gonococcal or E. coli RecA proteins or high pH, and
autoproteolysis requires the active and cleavage site residues conserved
between LexA and NG1427. NG1427 controls a three gene regulon: itself;
ng1428, a Neisseria-specific, putative integral membrane protein;
and recN, a DNA repair gene known to be required for oxidative damage
survival. Full NG1427 regulon de-repression requires RecA following
methyl methanesulphonate or mitomycin C treatment, but is largely
RecA-independent following hydrogen peroxide treatment. NG1427 binds
specifically to the operator regions of the genes it controls, and
DNA binding is abolished by oxidation of the single cysteine residue
encoded in NG1427. We propose that NG1427 is inactivated independently
of RecA by oxidation.},
doi = {10.1111/j.1365-2958.2010.07491.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07491.x}
}
@ARTICLE{Schostak2007,
author = {Schostak, Martin and Krause, Hans and Miller, Kurt and Schrader,
Mark and Kempkensteffen, Carsten and Kollermann, Jens},
title = {Does the molecular staging in pelvic lymph nodes improve the detection
of relevant prostate cancer metastases? An assessment after 6Â years},
journal = {BJU International},
year = {2007},
volume = {99},
pages = {1409--1414},
number = {6},
abstract = {OBJECTIVE To assess the course of cancer-free survival and thus determine
how reliably reverse transcriptase-polymerase chain reaction (RT-PCR)
can detect prostate-specific antigen (PSA)-expressing cells, as patients
with untreated lymph node-positive prostate cancer tend to have a
poor prognosis, whereas those treated with radical prostatectomy
(RP) and immediate adjuvant hormonal therapy show excellent local
disease control and a disease-free survival comparable with that
of patients with negative lymph nodes, but the detection of micrometastatic
disease in pelvic lymph nodes remains a major challenge. PATIENTS
AND METHODS Quantitative RT-PCR was used to detect PSA mRNA expression
in total RNA of 457 pelvic lymph nodes from 70 patients who had RP
(53 patients) or laparoscopic lymphadenectomy (17) at our clinic
in 1999/2000. For this purpose, alternate sections of lymph node
tissue were either snap-frozen for later RNA isolation or examined
by standard histopathological methods. Clinicopathological data,
adjuvant treatments and follow-up data were recorded for all patients.
RESULTS After January 2006 (6-year observation period), 13 patients
had no follow-up data, while 27 had biochemical (PSA) recurrence
or other evidence of clinical progression (two died from prostate
cancer), and 30 had no signs of recurrence. Compared to the ‘reference’
standard (histopathology), the PCR method had a sensitivity of 83%
and a specificity of 66%. The method had a positive predictive value
of 52% and a negative predictive value of 57%. CONCLUSION Considered
alone, pelvic lymph node PSA RT-PCR does not predict the clinical
course better than a histopathological assessment of lymph nodes.
However, it also identifies some patients with negative histology
who later show progression. When added to the pathological classification,
PSA RT-PCR improves the detection rate of primary lymphatic dissemination.},
issn = {1464-410X},
keywords = {prostate cancer, molecular staging, PSA, RT-PCR, lymph node metastases,
prognostic significance},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-410X.2007.06861.x}
}
@ARTICLE{Schostak2006,
author = {Schostak, Martin and Miller, Kurt and Krause, Hans and Schrader,
Mark and Kempkensteffen, Carsten and Kollermann, Jens},
title = {Kinetic fluorescence reverse transcriptase-polymerase chain reaction
for alpha-methylacyl CoA racemase distinguishes prostate cancer from
benign lesions},
journal = {Cancer Detection and Prevention},
year = {2006},
volume = {30},
pages = {449--454},
number = {5},
abstract = {Background: High-throughput gene expression profiling has recently
shown that the mRNA for alpha-methylacyl CoA racemase (AMACR or P504S)
is overexpressed in prostate carcinomas (PCa). Several immunohistochemical
studies have reported the usefulness of anti-AMACR/P504S for detecting
prostate cancer over the full range of prostate specimens encountered
in surgical pathology. We tested real-time reverse transcriptase-polymerase
chain reaction (RT-PCR) for specific and sensitive detection of AMACR
transcripts as a supplementary measure for discriminating between
malignant and benign lesions in prostatic tissues. Methods: Total
RNA was isolated from snap-frozen chips in 55 cases of benign prostatic
hyperplasia (BPH) and from frozen sections in 57 prostatectomy cases.
The latter were analyzed by an uropathologist (J.K.) and found to
contain at least 50% malignant epithelia. Relative quantification
of AMACR transcripts was performed by RT-PCR using hybridization
probes for detection and PBGD for normalization. Results: Normalized
AMACR transcript levels showed an average 3.75-fold increase in 57
prostate carcinomas cases when compared to 55 cases of BPH (p < 0.0001).
A 85.6% specificity and 64.9% sensitivity can be achieved if the
cutoff is set at 12.95. AMACR expression levels among PCa cases were
not statistically associated with the tumor and lymph node stage,
the grading, the surgical margins, the Gleason score or progression.
Discussion: The present study demonstrates the usefulness of quantitative
AMACR-mRNA transcript detection in prostatic tissues as an alternative
to immunological staining techniques. Since the latter clearly predominate
in the laboratory routine, PCR-based detection of AMACR has the potential
to gain widespread acceptance as a suitable future tool for monitoring
prostate cancer patients.},
issn = {0361-090X},
keywords = {Prostate cancer, AMACR, P504S, RT-PCR, mRNA, Quantitative detection,
Prostate-specific antigen (PSA), Immunohistochemical antibodies,
Benign prostatic hyperplasia (BPH), Nuclear atypia, Cytokeratin,
mRNA analysis, Tumor stage, Pathological classification, Gleason
score, Clinical progression, Predictive values},
url = {http://www.sciencedirect.com/science/article/B6X28-4M69JDJ-3/2/b83f99c8d5ff2331f3bbf086b840c4e1}
}
@ARTICLE{Schothorst2009,
author = {van Schothorst, Evert and Flachs, Pavel and Franssen-van Hal, Nicole
and Kuda, Ondrej and Bunschoten, Annelies and Molthoff, Jos and Vink,
Carolien and Hooiveld, Guido and Kopecky, Jan and Keijer, Jaap},
title = {Induction of lipid oxidation by polyunsaturated fatty acids of marine
origin in small intestine of mice fed a high-fat diet},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {110},
number = {1},
abstract = {BACKGROUND:Dietary polyunsaturated fatty acids (PUFA), in particular
the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic
(EPA), are linked to many health benefits in humans and in animal
models. Little is known of the molecular response to DHA and EPA
of the small intestine, and the potential contribution of this organ
to the beneficial effects of these fatty acids. Here, we assessed
gene expression changes induced by DHA and EPA in the wildtype C57BL/6J
murine small intestine using whole genome microarrays and functionally
characterized the most prominent biological process.RESULTS:The main
biological process affected based on gene expression analysis was
lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial
beta-oxidation, and omega-oxidation of fatty acids were all increased.
Quantitative real time PCR, and -in a second animal experiment- intestinal
fatty acid oxidation measurements confirmed significant gene expression
differences and showed in a dose-dependent manner significant changes
at biological functional level. Furthermore, no major changes in
the expression of lipid metabolism genes were observed in the colon.CONCLUSION:We
show that marine n-3 fatty acids regulate small intestinal gene expression
and increase fatty acid oxidation. Since this organ contributes significantly
to whole organism energy use, this effect on the small intestine
may well contribute to the beneficial physiological effects of marine
PUFAs under conditions that will normally lead to development of
obesity, insulin resistance and diabetes.},
doi = {10.1186/1471-2164-10-110},
issn = {1471-2164},
pubmedid = {19284886},
url = {http://www.biomedcentral.com/1471-2164/10/110}
}
@ARTICLE{Schotte2011,
author = {Schotte, Diana and De Menezes, Renee X. and Moqadam, Farhad Akbari
and Khankahdani, Leila Mohammadi and Lange-Turenhout, Ellen and Chen,
Caifu and Pieters, Rob and Den Boer, Monique L.},
title = {MicroRNA characterize genetic diversity and drug resistance in pediatric
acute lymphoblastic leukemia},
journal = {Haematologica},
year = {2011},
volume = {96},
pages = {703--711},
number = {5},
month = may,
abstract = {BackgroundMicroRNA regulate the activity of protein-coding genes including
those involved in hematopoietic cancers. The aim of the current study
was to explore which microRNA are unique for seven different subtypes
of pediatric acute lymphoblastic leukemia. Design and MethodsExpression
levels of 397 microRNA (including novel microRNA) were measured by
quantitative real-time polymerase chain reaction in 81 cases of pediatric
leukemia and 17 normal hematopoietic control cases. ResultsAll major
subtypes of acute lymphoblastic leukemia, i.e. T-cell, MLL-rearranged,
TEL-AML1-positive, E2A-PBX1-positive and hyperdiploid acute lymphoblastic
leukemia, with the exception of BCR-ABL-positive and B-other' acute
lymphoblastic leukemias (defined as precursor B-cell acute lymphoblastic
leukemia not carrying the foregoing cytogenetic aberrations), were
found to have unique microRNA-signatures that differed from each
other and from those of healthy hematopoietic cells. Strikingly,
the microRNA signature of TEL-AML1-positive and hyperdiploid cases
partly overlapped, which may suggest a common underlying biology.
Moreover, aberrant down-regulation of let-7b (~70-fold) in MLL-rearranged
acute lymphoblastic leukemia was linked to up-regulation of oncoprotein
c-Myc (PFDR<0.0001). Resistance to vincristine and daunorubicin was
characterized by an approximately 20-fold up-regulation of miR-125b,
miR-99a and miR-100 (PFDR[≤]0.002). No discriminative microRNA
were found for prednisolone response and only one microRNA was linked
to resistance to L-asparaginase. A combined expression profile based
on 14 microRNA that were individually associated with prognosis,
was highly predictive of clinical outcome in pediatric acute lymphoblastic
leukemia (5-year disease-free survival of 89.4%{+/-}7% versus 60.8{+/-}12%,
P=0.001). ConclusionsGenetic subtypes and drug-resistant leukemic
cells display characteristic microRNA signatures in pediatric acute
lymphoblastic leukemia. Functional studies of discriminative and
prognostically important microRNA may provide new insights into the
biology of pediatric acute lymphoblastic leukemia.},
comment = {10.3324/haematol.2010.026138},
url = {http://www.haematologica.org/cgi/content/abstract/96/5/703}
}
@ARTICLE{Schotte2010,
author = {Schotte, Diana and Lange-Turenhout, Ellen A.M. and Stumpel, Dominique
J.P.M. and Stam, Ronald W. and Buijs-Gladdines, Jessica G.C.A.M.
and Meijerink, Jules P.P. and Pieters, Rob and Den Boer, Monique
L.},
title = {Expression of miR-196b is not exclusively MLL-driven but is especially
linked to activation of HOXA genes in pediatric acute lymphoblastic
leukemia},
journal = {Haematologica},
year = {2010},
volume = {95},
pages = {1675--1682},
number = {10},
month = oct,
abstract = {BackgroundDeregulation of microRNA may contribute to hematopoietic
malignancies. MicroRNA-196b (miR-196b) is highly expressed in MLL-rearranged
leukemia and has been shown to be activated by MLL and MLL-fusion
genes. Design and MethodsIn order to determine whether high expression
of miR-196b is restricted to MLL-rearranged leukemia, we used quantitative
stem-loop reverse transcriptase polymerase chain reaction to measure
the expression of this microRNA in 72 selected cases of pediatric
acute lymphoblastic leukemia i.e. MLL-rearranged and non-MLL-rearranged
precursor B-cell and T-cell acute lymphoblastic leukemias. We also
determined the expression of HOXA-genes flanking miR-196 by microarray
and real-time quantitative polymerase chain reaction. Furthermore,
we used CpG island-arrays to explore the DNA methylation status of
miR-196b and HOXA. ResultsWe demonstrated that high expression of
miR-196b is not unique to MLL-rearranged acute lymphoblastic leukemia
but also occurs in patients with T-cell acute lymphoblastic leukemia
patients carrying CALM-AF10, SET-NUP214 and inversion of chromosome
7. Like MLL-rearrangements, these abnormalities have been functionally
linked with up-regulation of HOXA. In correspondence, miR-196b expression
in these patients correlated strongly with the levels of HOXA family
genes (Spearman's correlation coefficient [≥] 0.7; P[≤]0.005).
Since miR-196b is encoded on the HOXA cluster, these data suggest
co-activation of miR-196b and HOXA genes in acute lymphoblastic leukemia.
Up-regulation of miR-196b coincides with reduced DNA methylation
at CpG islands in the promoter regions of miR-196b and the entire
HOXA cluster in MLL-rearranged cases compared to in cases of non-MLL
precursor B-cell acute lymphoblastic leukemia and normal bone marrow
(P<0.05), suggesting an epigenetic origin for miR-196b over-expression.
Although patients with MLL-rearranged acute lymphoblastic leukemia
are highly resistant to prednisolone and L-asparaginase, this resistance
was not attributed to miR-196b expression. ConclusionsHigh expression
of miR-196b is not exclusively MLL-driven but can also be found in
other types of leukemia with aberrant activation of HOXA genes. Since
miR-196b has been shown by others to exert oncogenic activity in
bone marrow progenitor cells, the findings of the present study imply
a potential role for miR-196b in the underlying biology of all HOXA-activated
leukemias.},
url = {http://www.haematologica.org/cgi/content/abstract/95/10/1675}
}
@ARTICLE{Schotte2011a,
author = {Schotte, D and Moqadam, F Akbari and Lange-Turenhout, E A M and Chen,
C and van IJcken, W F J and Pieters, R and den Boer, M L},
title = {Discovery of new microRNAs by small RNAome deep sequencing in childhood
acute lymphoblastic leukemia},
journal = {Leukemia},
year = {2011},
pages = {--},
month = may,
issn = {1476-5551},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/leu.2011.105}
}
@ARTICLE{Schraders2008,
author = {Schraders, Margit and Jares, Pedro and Bea, Silvia and Schoenmakers,
Eric F. P. M. and Van Krieken, Johan H. J. M. and Campo, Elias and
Groenen, Patricia J. T. A.},
title = {Integrated genomic and expression profiling in mantle cell lymphoma:
identification of gene-dosage regulated candidate genes},
journal = {British Journal of Haematology},
year = {2008},
volume = {143},
pages = {210--221},
number = {2},
abstract = {Summary Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32)
translocation and several other cytogenetic aberrations, including
heterozygous loss of chromosomal arms 1p, 6q, 11q and 13q and/or
gains of 3q and 8q. The common intervals of chromosomal imbalance
have been narrowed down using array-comparative genomic hybridization
(CGH). However, the chromosomal intervals still contain many genes
potentially involved in MCL pathogeny. Combined analysis of tiling-resolution
array-CGH with gene expression profiling on 11 MCL tumours enabled
the identification of genomic alterations and their corresponding
gene expression profiles. Only subsets of genes located within given
cytogenetic anomaly-intervals showed a concomitant change in mRNA
expression level. The genes that showed consistent correlation between
DNA copy number and RNA expression levels are likely to be important
in MCL pathology. Besides several ‘anonymous genes’, we also
identified various fully annotated genes, whose gene products are
involved in cyclic adenosine monophosphate-regulated pathways (PRKACB),
DNA damage repair, maintenance of chromosome stability and prevention
of rereplication (ATM, ERCC5, FBXO5), energy metabolism (such as
genes that are involved in the synthesis of proteins encoded by the
mitochondrial genome) and signal transduction (ARHGAP29). Deregulation
of these gene products may interfere with the signalling pathways
that are involved in MCL tumour development and maintenance.},
issn = {1365-2141},
keywords = {mantle cell lymphoma, expression profiling, array-CGH, data integration,
gene-dosage},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2008.07334.x}
}
@ARTICLE{Schreibelt2008,
author = {Schreibelt, Gerty and van Horssen, Jack and Haseloff, Reiner F. and
Reijerkerk, Arie and van der Pol, Susanne M.A. and Nieuwenhuizen,
Orm and Krause, Eberhard and Blasig, Ingolf E. and Dijkstra, Christine
D. and Ronken, Eric and de Vries, Helga E.},
title = {Protective effects of peroxiredoxin-1 at the injured blood-brain
barrier},
journal = {Free Radical Biology and Medicine},
year = {2008},
volume = {45},
pages = {256--264},
number = {3},
month = aug,
abstract = {Reactive oxygen species (ROS) play a pivotal role in the development
of neuroinflammatory disorders, such as multiple sclerosis (MS).
Here, we studied the effect of ROS on protein expression in brain
endothelial cells (BECs) using proteomic techniques and show that
long-term exposure to ROS induces adaptive responses in BECs to counteract
an oxidative attack. ROS induce differential protein expression in
BECs, among which is peroxiredoxin-1 (Prx1). To further study the
role of Prx1 we established a BEC line overexpressing Prx1. Our data
indicate that Prx-1 overexpression protects BECs from ROS-induced
cell death, reduces adhesion and subsequent transendothelial migration
of monocytes by decreasing intercellular adhesion molecule-1 expression,
and enhances the integrity of the BEC layer. Interestingly, vascular
Prx1 immunoreactivity was markedly upregulated in inflammatory lesions
of experimental autoimmune encephalomyelitis (EAE) animals and active
demyelinating MS lesions. These findings indicate that enhanced vascular
Prx1 expression may reflect the occurrence of vascular oxidative
stress in EAE and MS. On the other hand, it may function as an endogenous
defense mechanism to inhibit leukocyte infiltration and counteract
ROS-induced cellular injury.},
issn = {0891-5849},
keywords = {Blood-brain barrier, Multiple sclerosis, Neuroinflammation, Oxidative
stress, Peroxiredoxin-1, Reactive oxygen species},
url = {http://www.sciencedirect.com/science/article/B6T38-4S98TWN-1/2/9761aec912cece98eeef8fc939e20427}
}
@ARTICLE{Schreiber2009,
author = {Schreiber, Taylor H. and Deyev, Vadim V. and Rosenblatt, Joseph D.
and Podack, Eckhard R.},
title = {Tumor-Induced Suppression of CTL Expansion and Subjugation by gp96-Ig
Vaccination},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {2026--2033},
number = {5},
month = mar,
abstract = {Established tumors suppress antitumor immune responses and induce
tolerance by incompletely characterized mechanisms, and this phenomenon
is an important barrier to tumor immunotherapy. Single vaccination
with tumor cells expressing gp96-Ig stimulates robust expansion of
tumor-specific CTLs in tumor-naive mice and this expansion is inhibited
by established tumors. Interestingly, frequent vaccinations restore
antitumor immune responses in the presence of established tumors.
Syngeneic EG7 tumor-bearing mice have heterogeneous responses to
frequent vaccination with EG7-gp96-Ig, with 32% complete responders
and 68% partial responders. Comparison of responders to nonresponders
revealed an inverse correlation between tumor-specific CTL expansion
in the peripheral blood and tumor size. To identify immune cells
and molecules associated with effective antitumor immune responses,
reverse transcription-PCR arrays were performed using cells isolated
from the vaccination site. ELISAs, cellular phenotyping, and tumor
immunohistochemistry were also performed comparing vaccine responders
to nonresponders. These data show that up-regulation of T-bet, ROR{gamma}t,
IFN{gamma}, CCL8, CXCL9, and CXCL10 at the vaccination site are associated
with vaccine-induced antitumor immunity. These data correlate with
increased CTL expansion in the peripheral blood of responders, increased
infiltration of responder tumors by CD8+ cells and interleukin-17+
cells, and decreased infiltration of responder tumors by CD11b+Gr-1+
cells and FoxP3+ cells. Furthermore, serum ELISAs revealed a significant
elevation of transforming growth factor-{beta} in nonresponders as
compared with responders. Interestingly, CD8+ T cells isolated from
responders and nonresponders have equivalent cytotoxic activity in
vitro. Taken together, our data suggest that established tumors may
escape immunosurveillance by preventing clonal expansion of tumor-specific
CTL without inducing anergy. [Cancer Res 2009;69(5):2026-33]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/5/2026}
}
@ARTICLE{Schreiner2009,
author = {Schreiner, Claire M. and Bell, Sheila M. and Scott, William J.},
title = {Microarray analysis of murine limb bud ectoderm and mesoderm after
exposure to cadmium or acetazolamide},
journal = {Birth Defects Research Part A: Clinical and Molecular Teratology},
year = {2009},
volume = {85},
pages = {588--598},
number = {7},
abstract = {Abstract 10.1002/bdra.20577.abs BACKGROUND: A variety of drugs, environmental
chemicals, and physical agents induce a common limb malformation
in the offspring of pregnant mice exposed on day 9 of gestation.
This malformation, postaxial, right-sided forelimb ectrodactyly,
is thought to arise via an alteration of hedgehog signaling. METHODS:
We have studied two of these teratogens, acetazolamide and cadmium,
using the technique of microarray analysis of limb bud ectoderm and
mesoderm to search for changes in gene expression that could indicate
a common pathway to postaxial limb reduction. RESULTS: Results indicated
a generalized up-regulation of gene expression after exposure to
acetazolamide but a generalized down-regulation due to cadmium exposure.
An intriguing observation was a cadmium-induced reduction of Mt1
and Mt2 expression in the limb bud mesoderm indicating a lowering
of embryonic zinc. CONCLUSIONS: We propose that these two teratogens
and others (valproic acid and ethanol) lower sonic hedgehog signaling
by perturbation of zinc function in the sonic hedgehog protein. Birth
Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc.},
issn = {1542-0760},
keywords = {microarray, cadmium, acetazolamide, limb buds},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bdra.20577}
}
@ARTICLE{Schreur2011,
author = {Schreur, Paul J. Wichgers and Rebel, Johanna M. J. and Smits, Mari
A. and van Putten, Jos P. M. and Smith, Hilde E.},
title = {TroA of Streptococcus suis Is Required for Manganese Acquisition
and Full Virulence},
journal = {J. Bacteriol.},
year = {2011},
volume = {193},
pages = {5073-5080},
number = {19},
abstract = {Streptococcus suis causes infections in pigs and occasionally in humans,
resulting in manifestations as meningitis, sepsis, arthritis, and
septic shock. For survival within the host, S. suis requires numerous
nutrients including trace metals. Little is known about the specific
proteins involved in metal scavenging in S. suis. In this study we
evaluated the role of the putative high-affinity metal binding lipoprotein
TroA in metal acquisition and virulence. A mutant strain deficient
in the expression of TroA ({Delta}troA mutant) was constructed. Growth
of the {Delta}troA mutant in Todd-Hewitt broth was similar to wild-type
growth; however, growth of the {Delta}troA mutant in cation-deprived
Todd-Hewitt broth and in porcine serum was strongly reduced compared
to growth of wild-type bacteria. Supplementing the medium with extra
manganese but not with magnesium, zinc, copper, nickel, or iron restored
growth to wild-type levels, indicating that TroA is specifically
required for growth in environments low in manganese. The {Delta}troA
mutant also showed increased susceptibility to H2O2, suggesting that
TroA is involved in counteracting oxidative stress. Furthermore,
the expression of the troA gene was subject to environmental regulation
at the transcript level. In a murine S. suis infection model, the
{Delta}troA mutant displayed a nonvirulent phenotype. These data
indicate that S. suis TroA is involved in manganese acquisition and
is required for full virulence in mice.},
doi = {10.1128/JB.05305-11},
eprint = {http://jb.asm.org/cgi/reprint/193/19/5073.pdf},
url = {http://jb.asm.org/cgi/content/abstract/193/19/5073}
}
@ARTICLE{Schriek2008,
author = {Schriek, Sarah and Aguirre-von-Wobeser, Eneas and Nodop, Anke and
Becker, Anke and Ibelings, Bas W. and Bok, Jasper and Staiger, Dorothee
and Matthijs, Hans C. P. and Pistorius, Elfriede K. and Michel, Klaus-Peter},
title = {Transcript profiling indicates that the absence of PsbO affects the
coordination of C and N metabolism in Synechocystis sp. PCC 6803},
journal = {Physiologia Plantarum},
year = {2008},
volume = {133},
pages = {525--543},
number = {3},
abstract = {Transcript profiling of nitrate-grown Synechocystis sp. PCC 6803 PsbO-free
mutant cells in comparison to wild-type (WT) detected substantial
deviations. Because we had previously observed phenotypical differences
between Synechocystis sp. PCC 6803 WT and its corresponding PsbO-free
mutant when cultivated with l-arginine as sole N source and a light
intensity of 200 μmol photons m−2 s−1, we also performed
transcript profiling for both strains grown either with nitrate or
with l-arginine as sole N source. We observed a total number of 520
differentially regulated transcripts in Synechocystis WT because
of a shift from nitrate- to l-arginine-containing BG11 medium, while
we detected only 13 differentially regulated transcripts for the
PsbO-free mutant. Thus, the PsbO-free Synechocystis mutant had already
undergone a preconditioning process for growth with l-arginine in
comparison to WT. While Synechocystis WT suffered from growth with
l-arginine at a light intensity of 200 μmol photons m−2 s−1,
the PsbO-free mutant developed only a minor stress phenotype. In
summary, our results suggest that the absence of PsbO in Synechocystis
affects the coordination of photosynthesis/respiration and l-arginine
metabolism through complex probably redox-mediated regulatory pathways.
In addition, we show that a comparison of the transcriptomes of nitrate-grown
Synechococcus elongatus PCC 7942 WT cells and its corresponding PsbO-free
mutant cells resulted in only a few differentially regulated transcripts
between both strains. The absence of the manganese/calcium-stabilizing
PsbO protein of PSII with an assigned regulatory function for photosynthetic
water oxidation causes bigger changes in the transcriptome of the
permissive photoheterotrophically growing Synechocystis sp. PCC 6803
than in the transcriptome of the obligate photoautotrophically growing
S. elongatus PCC 7942.},
issn = {1399-3054},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-3054.2008.01119.x}
}
@ARTICLE{Schriek2009,
author = {Schriek, Sarah and Kahmann, Uwe and Staiger, Dorothee and Pistorius,
Elfriede K. and Michel, Klaus-Peter},
title = {Detection of an L-amino acid dehydrogenase activity in Synechocystis
sp. PCC 6803},
journal = {J. Exp. Bot.},
year = {2009},
volume = {60},
pages = {1035--1046},
number = {3},
month = mar,
abstract = {The protein Slr0782 from Synechocystis sp. PCC 6803, which has similarity
to L-amino acid oxidase from Synechococcus elongatus PCC 6301 and
PCC 7942, has been characterized in part. Immunoblot blot analysis
showed that Slr0782 is mainly thylakoid membrane-associated. Moreover,
expression of slr0782 mRNA and Slr0782 protein were analyzed and
an activity assay was developed. Utilizing toluene-permeabilized
cells, an L-arginine-stimulated O2 uptake became detectable in Synechocystis
sp. PCC 6803. Besides oxidizing the basic L-amino acids L-arginine,
L-lysine, L-ornithine, and L-histidine, a number of other L-amino
acids were also substrates, while D-amino acids were not. The best
substrate was L-cysteine, and the second best was L-arginine. The
L-arginine-stimulated O2 uptake was inhibited by cations. The inhibition
by o-phenanthroline and salicylhydroxamic acid suggested the presence
of a transition metal besides FAD in the enzyme. Moreover, it is
shown that inhibitors of the respiratory electron transport chain,
such as KCN and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone,
also inhibited the L-arginine-stimulated O2 uptake, suggesting that
Slr0782 functions as an L-arginine dehydrogenase, mediating electron
transfer from L-arginine into the respiratory electron transport
chain utilizing O2 as electron acceptor via cytochrome oxidase. The
results imply that Slr0782 is an additional substrate dehydrogenase
being able to interact with the electron transport chain of the thylakoid
membrane.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/60/3/1035}
}
@ARTICLE{Schrimpe2009,
author = {Schrimpe, Alexandra C. and Wright, David W.},
title = {Comparative Analysis of Gene Expression Changes Mediated by Individual
Constituents of Hemozoin},
journal = {Chemical Research in Toxicology},
year = {2009},
volume = {22},
pages = {433-445},
number = {3},
note = {PMID: 19191707},
doi = {10.1021/tx8002752},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx8002752},
url = {http://pubs.acs.org/doi/abs/10.1021/tx8002752}
}
@ARTICLE{Schroeckh2009,
author = {Schroeckh, Volker and Scherlach, Kirstin and Nutzmann, Hans-Wilhelm
and Shelest, Ekaterina and Schmidt-Heck, Wolfgang and Schuemann,
Julia and Martin, Karin and Hertweck, Christian and Brakhage, Axel
A.},
title = {Intimate bacterial-fungal interaction triggers biosynthesis of archetypal
polyketides in Aspergillus nidulans},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {14558--14563},
number = {34},
month = aug,
abstract = {Fungi produce numerous low molecular weight molecules endowed with
a multitude of biological activities. However, mining the full-genome
sequences of fungi indicates that their potential to produce secondary
metabolites is greatly underestimated. Because most of the biosynthesis
gene clusters are silent under laboratory conditions, one of the
major challenges is to understand the physiological conditions under
which these genes are activated. Thus, we cocultivated the important
model fungus Aspergillus nidulans with a collection of 58 soil-dwelling
actinomycetes. By microarray analyses of both Aspergillus secondary
metabolism and full-genome arrays and Northern blot and quantitative
RT-PCR analyses, we demonstrate at the molecular level that a distinct
fungal-bacterial interaction leads to the specific activation of
fungal secondary metabolism genes. Most surprisingly, dialysis experiments
and electron microscopy indicated that an intimate physical interaction
of the bacterial and fungal mycelia is required to elicit the specific
response. Gene knockout experiments provided evidence that one induced
gene cluster codes for the long-sought after polyketide synthase
(PKS) required for the biosynthesis of the archetypal polyketide
orsellinic acid, the typical lichen metabolite lecanoric acid, and
the cathepsin K inhibitors F-9775A and F-9775B. A phylogenetic analysis
demonstrates that orthologs of this PKS are widespread in nature
in all major fungal groups, including mycobionts of lichens. These
results provide evidence of specific interaction among microorganisms
belonging to different domains and support the hypothesis that not
only diffusible signals but intimate physical interactions contribute
to the communication among microorganisms and induction of otherwise
silent biosynthesis genes.},
url = {http://www.pnas.org/cgi/content/abstract/106/34/14558}
}
@ARTICLE{Schroeder2006,
author = {Schroeder, A and Mueller, O and Stocker, S and Salowsky, R and Leiber,
M and Gassmann, M and Lightfoot, S and Menzel, W and Granzow, M and
Ragg, T},
title = {The RIN: an RNA integrity number for assigning integrity values to
RNA measurements.},
journal = {BMC Mol Biol},
year = {2006},
volume = {7},
pages = {3--},
month = jan,
abstract = {BACKGROUND: The integrity of RNA molecules is of paramount importance
for experiments that try to reflect the snapshot of gene expression
at the moment of RNA extraction. Until recently, there has been no
reliable standard for estimating the integrity of RNA samples and
the ratio of 28S:18S ribosomal RNA, the common measure for this purpose,
has been shown to be inconsistent. The advent of microcapillary electrophoretic
RNA separation provides the basis for an automated high-throughput
approach, in order to estimate the integrity of RNA samples in an
unambiguous way. METHODS: A method is introduced that automatically
selects features from signal measurements and constructs regression
models based on a Bayesian learning technique. Feature spaces of
different dimensionality are compared in the Bayesian framework,
which allows selecting a final feature combination corresponding
to models with high posterior probability. RESULTS: This approach
is applied to a large collection of electrophoretic RNA measurements
recorded with an Agilent 2100 bioanalyzer to extract an algorithm
that describes RNA integrity. The resulting algorithm is a user-independent,
automated and reliable procedure for standardization of RNA quality
control that allows the calculation of an RNA integrity number (RIN).
CONCLUSION: Our results show the importance of taking characteristics
of several regions of the recorded electropherogram into account
in order to get a robust and reliable prediction of RNA integrity,
especially if compared to traditional methods.},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413964/}
}
@ARTICLE{Schroeder2011,
author = {Schroeder, Diane I. and Lott, Paul and Korf, Ian and LaSalle, Janine
M.},
title = {Large-scale methylation domains mark a functional subset of neuronally
expressed genes},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1583-1591},
number = {10},
abstract = {DNA methylation is essential for embryonic and neuronal differentiation,
but the function of most genomic DNA methylation marks is poorly
understood. Generally the human genome is highly methylated (>70%)
except for CpG islands and gene promoters. However, it was recently
shown that the IMR90 human fetal lung fibroblast cells have large
regions of the genome with partially methylated domains (PMDs, <70%
average methylation), in contrast to the rest of the genome which
is in highly methylated domains (HMDs, >70% average methylation).
Using bisulfite conversion followed by high-throughput sequencing
(MethylC-seq), we discovered that human SH-SY5Y neuronal cells also
contain PMDs. We developed a novel hidden Markov model (HMM) to computationally
map the genomic locations of PMDs in both cell types and found that
autosomal PMDs can be >9 Mb in length and cover 41% of the IMR90
genome and 19% of the SH-SY5Y genome. Genomic regions marked by cell
line specific PMDs contain genes that are expressed in a tissue-specific
manner, with PMDs being a mark of repressed transcription. Genes
contained within N-HMDs (neuronal HMDs, defined as a PMD in IMR90
but HMD in SH-SY5Y) were significantly enriched for calcium signaling,
synaptic transmission, and neuron differentiation functions. Autism
candidate genes were enriched within PMDs and the largest PMD observed
in SH-SY5Y cells marked a 10 Mb cluster of cadherin genes with strong
genetic association to autism. Our results suggest that these large-scale
methylation domain maps could be relevant to interpreting and directing
future investigations into the elusive etiology of autism.},
doi = {10.1101/gr.119131.110},
eprint = {http://genome.cshlp.org/cgi/reprint/21/10/1583.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/10/1583}
}
@ARTICLE{Schroeter2011,
author = {Schroeter, Rebecca and Voigt, Birgit and Jürgen, Britta and Methling,
Karen and Pöther, Dierk-Christoph and Schäfer, Heinrich and Albrecht,
Dirk and Mostertz, Jörg and Mäder, Ulrike and Evers, Stefan and
Maurer, Karl-Heinz and Lalk, Michael and Mascher, Thorsten and Hecker,
Michael and Schweder, Thomas},
title = {The peroxide stress response of Bacillus licheniformis},
journal = {PROTEOMICS},
year = {2011},
volume = {11},
pages = {2851--2866},
number = {14},
abstract = {The oxidative stress response of Bacillus licheniformis after treatment
with hydrogen peroxide was investigated at the transcriptome, proteome
and metabolome levels. In this comprehensive study, 84 proteins and
467 transcripts were found to be up or downregulated in response
to the stressor. Among the upregulated genes were many that are known
to have important functions in the oxidative stress response of other
organisms, such as catalase, alkylhydroperoxide reductase or the
thioredoxin system. Many of these genes could be grouped into putative
regulons by genomic mining. The occurrence of oxidative damage to
proteins was analyzed by a 2-DE-based approach. In addition, we report
the induction of genes with hitherto unknown functions, which may
be important for the specific oxidative stress response of B. licheniformis.
The genes BLi04114 and BLi04115, that are located adjacent to the
catalase gene, were massively induced during peroxide stress. Furthermore,
the genes BLi04207 and BLi04208, which encode proteins homologous
to glyoxylate cycle enzymes, were also induced by peroxide. Metabolomic
analyses support the induction of the glyoxylate cycle during oxidative
stress in B. licheniformis.},
doi = {10.1002/pmic.201000461},
issn = {1615-9861},
keywords = {Bacillus licheniformis, Metabolome, Microbiology, Peroxide stress,
Transcriptome},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.201000461}
}
@ARTICLE{Schroeder2010,
author = {Schröder, Christine and Schumacher, Udo and Müller, Volkmar and Wirtz,
Ralph M. and Streichert, Thomas and Richter, Ulrich and Wicklein,
Daniel and Milde-Langosch, Karin},
title = {The transcription factor Fra-2 promotes mammary tumour progression
by changing the adhesive properties of breast cancer cells},
journal = {European Journal of Cancer},
year = {2010},
volume = {46},
pages = {1650--1660},
number = {9},
month = jun,
abstract = {The transcription factor Fra-2 (Fos-related antigen-2) has been implicated
in invasion of breast cancer cells, but there is only sparse information
about its role in clinical tumours. In the present study, we analysed
Fra-2 mRNA expression in a cohort of 167 patients, and found significant
correlations between high Fra-2 expression and nodal involvement
or reduced disease-free survival. To get more information about the
underlying mechanisms, we generated stably transfected MDA-MB231
breast cancer cells with increased Fra-2 expression. Compared with
the controls, these clones did not differ in proliferation and motility,
but had higher invasive potential. By global gene expression analysis
and subsequent validation of selected genes, we identified a number
of proteins involved in cell-cell or cell-matrix interactions that
were up- or down-regulated in Fra-2 overexpressing cells, e.g. connexin
43, ICAM-1, L1-CAM, integrin beta 2, integrin beta 4, and integrin
alpha 6. The association of Fra-2 overexpression and high ICAM-1
or L1-CAM levels could also be demonstrated in our clinical cohort
of mammary tumours. In both MDA-MB231 and MCF7 cells, we found an
increased attachment of Fra-2 transfectants to components of the
extracellular matrix. In addition, we could show a striking increase
in the number of rolling cells in flow-through assays using E-selectin
coated capillaries, which might indicate a higher capacity of extravasation.
In conclusion, our data obtained on breast cancer cell lines and
clinical tissue samples suggest that overexpression of Fra-2 promotes
breast cancer progression and metastasis by deregulation of genes
involved in cell-cell and cell-ECM contacts.},
issn = {0959-8049},
keywords = {Fra-2, Breast cancer, Metastasis, Adhesion, ICAM-1, L1CAM, c-Fos},
url = {http://www.sciencedirect.com/science/article/pii/S0959804910001115}
}
@ARTICLE{Schubbe2006,
author = {Schubbe, Sabrina and Wurdemann, Chris and Peplies, Jorg and Heyen,
Udo and Wawer, Cathrin and Glockner, Frank Oliver and Schuler, Dirk},
title = {Transcriptional Organization and Regulation of Magnetosome Operons
in Magnetospirillum gryphiswaldense},
journal = {Appl. Envir. Microbiol.},
year = {2006},
volume = {72},
pages = {5757--5765},
number = {9},
month = sep,
abstract = {Genes involved in magnetite biomineralization are clustered within
the genomic magnetosome island of Magnetospirillum gryphiswaldense.
Their transcriptional organization and regulation were studied by
several approaches. Cotranscription of genes within the mamAB, mamDC,
and mms clusters was demonstrated by reverse transcription-PCR (RT-PCR)
of intergenic regions, indicating the presence of long polycistronic
transcripts extending over more than 16 kb. The transcription start
points of the mamAB, mamDC, and mms operons were mapped at 22 bp,
52 bp, and 58 bp upstream of the first genes of the operons, respectively.
Identified -10 and -35 boxes of the PmamAB, PmamDC, and Pmms promoters
showed high similarity to the canonical {sigma}70 recognition sequence.
The transcription of magnetosome genes was further studied in response
to iron and oxygen. Transcripts of magnetosome genes were detected
by RT-PCR both in magnetic cells grown microaerobically under iron-sufficient
conditions and in nonmagnetic cells grown either aerobically or with
iron limitation. The presence of transcripts was found to be independent
of the growth phase. Further results from partial RNA microarrays
targeting the putative magnetosome transcriptome of M. gryphiswaldense
and real-time RT-PCR experiments indicated differences in expression
levels depending on growth conditions. The expression of the mam
and mms genes was down-regulated in nonmagnetic cells under iron
limitation and, to a lesser extent, during aerobic growth compared
to that in magnetite-forming cells grown microaerobically under iron-sufficient
conditions.},
url = {http://aem.asm.org/cgi/content/abstract/72/9/5757}
}
@ARTICLE{Schubert2008,
author = {Schubert, Stephanie and Kamino, Kenji and Bohm, Detlef and Adham,
Ibrahim and Engel, Wolfgang and Wasielewski, Reinhard von and Moharregh-Khiabani,
Darius and Mauceri, Grazia and Vaske, Bernhard and Meinhardt, Andreas
and Schoner, Anja and Gonzalez-Fassrainer, Daniela and Schmidtke,
Jorg},
title = {TSPY Expression Is Variably Altered in Transgenic Mice with Testicular
Feminization},
journal = {Biol Reprod},
year = {2008},
volume = {79},
pages = {125--133},
number = {1},
month = jul,
abstract = {TSPY (testis-specific protein, Y-encoded) genes are expressed in premeiotic
germ cells and round spermatids. The topology and timing of TSPY
expression, and also its homology to members of the TTSN-family,
suggest that TSPY is a proliferation factor for germ cells. There
is also evidence for a role of TSPY in the aetiology of testis cancer.
TSPY is a candidate for GBY, the elusive gonadoblastoma locus on
the human Y chromosome, which is thought to predispose dysgenetic
gonads of 46, XY sex-reversed females to develop gonadoblastoma.
We have previously generated a TSPY transgenic mouse line (Tg(TSPY)9Jshm)
that carries approximately 50 copies of the human TSPY gene on the
mouse Y chromosome. In order to elucidate TSPY expression under complete
androgen insensitivity and to investigate a possible role of TSPY
in gonadal tumorigenesis, we have now generated sex-reversed TSPY
transgenic ArTfm mice hemizygous for the X-linked testicular feminization
mutation (ArTfm). We can show that the TSPY transcript is aberrantly
spliced in the testes of TSPY-ArTfm mice, and that TSPY expression
is upregulated by androgen insensitivity in some but not all animals.
TSPY transgenic mice showed significantly increased testes weights.
In one TSPY transgenic ArTfm animal, spermatogenesis proceeded beyond
meiotic prophase. No tumors of germ cell origin were found in the
testes of TSPY-ArTfm mice. Five out of 46 TSPY transgenic ArTfm mice,
and 3 out of 31 age-related NMRI-ArTfm controls developed Leydig
cell tumors, whereas none of the age-matched ArTfm mice (n = 44)
on a wild type background were affected by Leydig cell tumorigenesis.},
url = {http://www.biolreprod.org/cgi/content/abstract/79/1/125}
}
@ARTICLE{Schuchardt2005,
author = {Schuchardt, Isabel and Assmann, Daniela and Thines, Eckhard and Schuberth,
Christian and Steinberg, Gero},
title = {Myosin-V, Kinesin-1, and Kinesin-3 Cooperate in Hyphal Growth of
the Fungus Ustilago maydis},
journal = {Mol. Biol. Cell},
year = {2005},
volume = {16},
pages = {5191--5201},
number = {11},
month = nov,
abstract = {Long-distance transport is crucial for polar-growing cells, such as
neurons and fungal hyphae. Kinesins and myosins participate in this
process, but their functional interplay is poorly understood. Here,
we investigate the role of kinesin motors in hyphal growth of the
plant pathogen Ustilago maydis. Although the microtubule plus-ends
are directed to the hyphal tip, of all 10 kinesins analyzed, only
conventional kinesin (Kinesin-1) and Unc104/Kif1A-like kinesin (Kinesin-3)
were up-regulated in hyphae and they are essential for extended hyphal
growth. {Delta}kin1 and {Delta}kin3 mutant hyphae grew irregular
and remained short, but they were still able to grow polarized. No
additional phenotype was detected in {Delta}kin1rkin3 double mutants,
but polarity was lost in {Delta}myo5rkin1 and {Delta}myo5rkin3 mutant
cells, suggesting that kinesins and class V myosin cooperate in hyphal
growth. Consistent with such a role in secretion, fusion proteins
of green fluorescent protein and Kinesin-1, Myosin-V, and Kinesin-3
accumulate in the apex of hyphae, a region where secretory vesicles
cluster to form the fungal Spitzenkorper. Quantitative assays revealed
a role of Kin3 in secretion of acid phosphatase, whereas Kin1 was
not involved. Our data demonstrate that just two kinesins and at
least one myosin support hyphal growth.},
url = {http://www.molbiolcell.org/cgi/content/abstract/16/11/5191}
}
@ARTICLE{Schuck2011,
author = {Schuck, Julie and Sun, Huifang and Penberthy, W Todd and Cooper,
Nigel and Li, Xiaohong and Smith, Michael},
title = {Transcriptomic analysis of the zebrafish inner ear points to growth
hormone mediated regeneration following acoustic trauma},
journal = {BMC Neuroscience},
year = {2011},
volume = {12},
pages = {88},
number = {1},
abstract = {BACKGROUND:Unlike mammals, teleost fishes are capable of regenerating
sensory inner ear hair cells that have been lost following acoustic
or ototoxic trauma. Previous work indicated that immediately following
sound exposure, zebrafish saccules exhibit significant hair cell
loss that recovers to pre-treatment levels within 14 days. Following
acoustic trauma in the zebrafish inner ear, we used microarray analysis
to identify genes involved in inner ear repair following acoustic
exposure. Additionally, we investigated the effect of growth hormone
(GH) on cell proliferation in control zebrafish utricles and saccules,
since GH was significantly up-regulated following acoustic trauma.RESULTS:Microarray
analysis, validated with the aid of quantitative real-time PCR, revealed
several genes that were highly regulated during the process of regeneration
in the zebrafish inner ear. Genes that had fold changes of [greater
than or equal to] 1.4 and P -values [less than or equal to] 0.05
were considered significantly regulated and were used for subsequent
analysis. Categories of biological function that were significantly
regulated included cancer, cellular growth and proliferation, and
inflammation. Of particular significance, a greater than 64-fold
increase in growth hormone (gh1) transcripts occurred, peaking at
2 days post-sound exposure (dpse) and decreasing to approximately
5.5-fold by 4 dpse. Pathway Analysis software was used to reveal
networks of regulated genes and showed how GH affected these networks.
Subsequent experiments showed that intraperitoneal injection of salmon
growth hormone significantly increased cell proliferation in the
zebrafish inner ear. Many other gene transcripts were also differentially
regulated, including heavy and light chain myosin transcripts, both
of which were down-regulated following sound exposure, and major
histocompatability class I and II genes, several of which were significantly
regulated on 2 dpse.CONCLUSIONS:Transcripts for GH, MHC Class I and
II genes, and heavy- and light-chain myosins, as well as many others
genes, were differentially regulated in the zebrafish inner ear following
overexposure to sound. GH injection increased cell proliferation
in the inner ear of non-sound-exposed zebrafish, suggesting that
GH could play an important role in sensory hair cell regeneration
in the teleost ear.},
doi = {10.1186/1471-2202-12-88},
issn = {1471-2202},
pubmedid = {21888654},
url = {http://www.biomedcentral.com/1471-2202/12/88}
}
@ARTICLE{Schuenemann2011,
author = {Schuenemann, Verena J. and Bos, Kirsten and DeWitte, Sharon and Schmedes,
Sarah and Jamieson, Joslyn and Mittnik, Alissa and Forrest, Stephen
and Coombes, Brian K. and Wood, James W. and Earn, David J. D. and
White, William and Krause, Johannes and Poinar, Hendrik N.},
title = {PNAS Plus: From the Cover: Targeted enrichment of ancient pathogens
yielding the pPCP1 plasmid of Yersinia pestis from victims of the
Black Death},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {E746-752},
number = {38},
abstract = {Although investigations of medieval plague victims have identified
Yersinia pestis as the putative etiologic agent of the pandemic,
methodological limitations have prevented large-scale genomic investigations
to evaluate changes in the pathogen's virulence over time. We screened
over 100 skeletal remains from Black Death victims of the East Smithfield
mass burial site (1348-1350, London, England). Recent methods of
DNA enrichment coupled with high-throughput DNA sequencing subsequently
permitted reconstruction of ten full human mitochondrial genomes
(16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid
at high coverage. Comparisons of molecular damage profiles between
endogenous human and Y. pestis DNA confirmed its authenticity as
an ancient pathogen, thus representing the longest contiguous genomic
sequence for an ancient pathogen to date. Comparison of our reconstructed
plasmid against modern Y. pestis shows identity with several isolates
matching the Medievalis biovar; however, our chromosomal sequences
indicate the victims were infected with a Y. pestis variant that
has not been previously reported. Our data reveal that the Black
Death in medieval Europe was caused by a variant of Y. pestis that
may no longer exist, and genetic data carried on its pPCP1 plasmid
were not responsible for the purported epidemiological differences
between ancient and modern forms of Y. pestis infections.},
doi = {10.1073/pnas.1105107108},
eprint = {http://www.pnas.org/cgi/reprint/108/38/E746.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/38/E746}
}
@ARTICLE{Schuetz2012,
author = {Audrey N. Schuetz and Richard C. Huard and Mark W. Eshoo and Christian
Massire and Phyllis Della-Latta and Fann Wu and Stephen G. Jenkins},
title = {Identification of a novel Acinetobacter baumannii clone in a US hospital
outbreak by multilocus polymerase chain reaction/electrospray-ionization
mass spectrometry},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2012},
volume = {72},
pages = {14 - 19},
number = {1},
abstract = {We investigated the relatedness of multidrug-resistant Acinetobacter
baumannii isolates from a burn intensive care unit (BICU) outbreak,
control isolates, and isolates from a previous 2007 outbreak by 3
molecular typing methods (repetitive sequence-based polymerase chain
reaction [rep-PCR], broad-range PCR and electrospray ionization mass
spectrometry [PCR/ESI-MS], and pulsed-field gel electrophoresis [PFGE]).
Partial rpoB gene sequencing confirmed all tested isolates as A.
baumannii. Molecular typing analysis showed that 17 of 19 outbreak
isolates were indistinguishable or closely related to each other.
Three of 4 non-BICU outbreak control isolates and 5Â of 6 isolates
from the previous outbreak closely matched the BICU outbreak genotype.
The outbreak strain represented a novel strain type, ST96, on PCR/ESI-MS
with a new combination of alleles not previously seen in the United
States. The ST96 strain also represented a novel rpoB Seqtype. Results
of PCR/ESI-MS and PFGE genotyping were most closely correlated, while
rep-PCR and PCR/ESI-MS systems generated rapid results.},
doi = {10.1016/j.diagmicrobio.2011.09.012},
issn = {0732-8893},
keywords = {Acinetobacter baumannii},
url = {http://www.sciencedirect.com/science/article/pii/S073288931100366X}
}
@ARTICLE{Schuetz2005,
author = {Schuetz, Audrey N. and Yin-Goen, Qiqin and Amin, Mahul B. and Moreno,
Carlos S. and Cohen, Cynthia and Hornsby, Christopher D. and Yang,
Wen Li and Petros, John A. and Issa, Muta M. and Pattaras, John G.
and Ogan, Kenneth and Marshall, Fray F. and Young, Andrew N.},
title = {Molecular Classification of Renal Tumors by Gene Expression Profiling},
journal = {J. Mol. Diagn.},
year = {2005},
volume = {7},
pages = {206--218},
number = {2},
month = may,
abstract = {Renal tumor classification is important because histopathological
subtypes are associated with distinct clinical behavior. However,
diagnosis is difficult because tumor subtypes have overlapping microscopic
characteristics. Therefore, ancillary methods are needed to optimize
classification. We used oligonucleotide microarrays to analyze 31
adult renal tumors, including clear cell renal cell carcinoma (RCC),
papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression
profiles correlated with histopathology; unsupervised algorithms
clustered 30 of 31 tumors according to appropriate diagnostic subtypes
while supervised analyses identified significant, subtype-specific
expression markers. Clear cell RCC overexpressed proximal nephron,
angiogenic, and immune response genes, chromophobe RCC oncocytoma
overexpressed distal nephron and oxidative phosphorylation genes,
papillary RCC overexpressed serine protease inhibitors, and extracellular
matrix products, and angiomyolipoma overexpressed muscle developmental,
lipid biosynthetic, melanocytic, and distinct angiogenic factors.
Quantitative reverse transcriptase-polymerase chain reaction and
immunohistochemistry of formalin-fixed renal tumors confirmed overexpression
of proximal nephron markers (megalin/low-density lipoprotein-related
protein 2, {alpha}-methylacyl CoA racemase) in clear cell and papillary
RCC and distal nephron markers ({beta}-defensin 1, claudin 7) in
chromophobe RCC/oncocytoma. In summary, renal tumor subtypes were
classified by distinct gene expression profiles, illustrating tumor
pathobiology and translating into novel molecular bioassays using
fixed tissue.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/7/2/206}
}
@ARTICLE{Schuetz2004,
author = {Schuetz, Christina and Neubauer, Hans and Bonin, Michael and Clare,
Susan E. and Sotlar, Karl and Riess, Olaf and Wallwiener, Diethelm
and Kurek, Raffael},
title = {Combination of lasermicrodissection and microarray analysis to determine
progression-specific molecular markers in breast cancer.},
journal = {AACR Meeting Abstracts},
year = {2004},
volume = {2004},
pages = {795-b--},
number = {1},
month = mar,
abstract = {Breast cancer is a complex, polygenic disease caused by mostly unknown
combinations of genetic and epigenetic anomalies which lead to lesions
with increasing risk of the development of invasive disease. Currently
used histopathological parameters are insufficient to identify ductal
carcinoma in situ (DCIS) with or without invasive potential. In order
to identify new progression-specific molecular markers, our laboratory
employed laser capture microdissection (LCM) to obtain homogenous
specimens of matched DCIS and invasive cells from five patients.
Approximately 20 000 cells (7000 laser pulses, 30{micro}m, Arcturus
PixCell II) were dissected from hematoxylin/eosin-stained frozen
sections (10{micro}m) and RNA was extracted. For linear amplification
of mRNA a protocol was successfully established starting with 50-100ng
of total RNA. Extensive quality controls before and after LCM, during
and after amplification were performed using the Agilent Bioanalyzer.
3'/5'-ratios of the generated probes, retrieved by hybridization
to Affymetrix test arrays, were uniformly low -indicating good quality
(HUMGAPDH/M33197: [~]1.5-2.5; HSAC07/X00351: [~]9-12). After hybridization
to Affymetrix full-density microarrays (human genome U133A), expression
profiles were analyzed and cluster analysis was performed. Differentially
expressed genes already associated with breast cancer were identified.
Examples are AXL (receptor tyrosine kinase), versican and fibronectin
(extra cellular matrix protein), PLAU (plasminogen activator), IGFBP
7 (insulin-like growth factor binding protein), and MVP (major vault
protein). Unknown and known genes not yet correlated with this disease
were confirmed as interesting candidate genes using quantitative
RT-PCR-analysis (Lightcycler, ROCHE). Functional analysis will be
performed. In summary, we have identified new molecular markers which
may characterize the transition from DCIS to invasive ductal carcinoma.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/795-b}
}
@ARTICLE{Schuetz2006,
author = {Schuetz, Christina S. and Bonin, Michael and Clare, Susan E. and
Nieselt, Kay and Sotlar, Karl and Walter, Michael and Fehm, Tanja
and Solomayer, Erich and Riess, Olaf and Wallwiener, Diethelm and
Kurek, Raffael and Neubauer, Hans J.},
title = {Progression-Specific Genes Identified by Expression Profiling of
Matched Ductal Carcinomas In situ and Invasive Breast Tumors, Combining
Laser Capture Microdissection and Oligonucleotide Microarray Analysis},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {5278--5286},
number = {10},
month = may,
abstract = {Becoming invasive is a crucial step in breast cancer oncogenesis.
At this point, a lesion carries the potential for spreading and metastasis--a
process, whose molecular characteristics still remain poorly understood.
In this article, we describe a matched-pair analysis of ductal carcinoma
in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast
ductal carcinomas to identify novel molecular markers characterizing
the transition from DCIS to IDC. The purpose of this study was to
better understand the molecular biology of this transition and to
identify candidate genes whose products might serve as prognostic
markers and/or as molecular targets for treatment. To obtain cellular-based
gene expression profiles from epithelial tumor cells, we combined
laser capture microdissection with a T7-based two-round RNA amplification
and Affymetrix oligonucleotide microarray analysis. Altogether, a
set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC
and replicate DCIS/IDC preparations from three of the nine tumors.
Cluster analysis on expression data shows the robustness and reproducibility
of the techniques we established. Using multiple statistical methods,
546 significantly differentially expressed probe sets were identified.
Eighteen candidate genes were evaluated by RT-PCR. Examples of genes
already known to be associated with breast cancer invasion are BPAG1,
LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C,
SART2, and TNFAIP6 was localized to epithelial tumor cells by in
situ hybridization and/or immunohistochemistry, confirming the accuracy
of laser capture microdissection sampling and microarray analysis.
(Cancer Res 2006; 66(10): 5278-86)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/10/5278}
}
@ARTICLE{Schuhmacher2010,
author = {Schuhmacher, Tom and Lemuth, Karin and Hardiman, Timo and Vacun,
Gabi and Reuss, Matthias and Siemann-Herzberg, Martin},
title = {Quantifying cytosolic messenger RNA concentrations in Escherichia
coli using real-time polymerase chain reaction for a systems biology
approach},
journal = {Analytical Biochemistry},
year = {2010},
volume = {398},
pages = {212--217},
number = {2},
month = mar,
abstract = {Current messenger RNA (mRNA) quantification methods are sophisticated
tools for the analysis of gene regulation. However, these methods
are not suitable for more complex quantitative approaches such as
the mathematical modeling of the in vivo regulation of transcription
where dynamic cytosolic mRNA concentrations need to be taken into
consideration. In the current study, the "standard curve method"
for quantitative reverse transcription real-time polymerase chain
reaction (qRT-PCR) was extended by including an internal RNA standard.
This standard enables transcript losses that occur during the process,
as well as variations resulting from nonquantitative processes, to
be accounted for. The use of an internal standard yielded transcript
concentration estimates that were on average seven times higher than
those in cases where an internal standard is omitted. Choosing the
cra modulon in Escherichia coli as an example, the method applied
shows that the regulation of the Cra protein, as well as the growth
rate-dependent regulation, need to be taken into consideration. The
new method, which enables the determination of cytosolic mRNA concentrations,
allows the quantitative representation of transcriptional dynamics.
This is an important aspect of the analysis of the complex interactions
of metabolism and regulation and in the application of mathematical
modeling for systems biology.},
issn = {0003-2697},
keywords = {Cytosolic mRNA concentrations, Absolute quantification, qRT-PCR, Internal
standard, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6W9V-4XRJX8Y-4/2/1775c6c7a9014c234435f29983a2ce92}
}
@ARTICLE{Schuierer2006,
author = {Schuierer, Marion M. and Heilmeier, Ursula and Boettcher, Alfred
and Ugocsai, Peter and Bosserhoff, Anja K. and Schmitz, Gerd and
Langmann, Thomas},
title = {Induction of Raf kinase inhibitor protein contributes to macrophage
differentiation},
journal = {Biochemical and Biophysical Research Communications},
year = {2006},
volume = {342},
pages = {1083--1087},
number = {4},
month = apr,
abstract = {Differential gene expression analysis of human blood monocytes has
identified the Raf kinase inhibitor protein (RKIP) as a continuously
upregulated gene in macrophage and dendritic cell maturation. Using
realtime RT-PCR and Western blot analysis we were able to confirm
the initial DNA-microarray findings of RKIP induction on mRNA and
protein levels. RKIP upregulation in primary cells and overexpression
in THP-1 cells did not alter ERK activity but strongly reduced the
amount of the NF[kappa]B subunit p65 in the nucleus. mRNA levels
and cell surface expression of maturation markers including the integrin
CD11c and the scavenger receptor CD36 were significantly increased
in RKIP transfected THP-1 cells. Our data show for the first time
that RKIP is upregulated during macrophage and dendritic cell differentiation
on mRNA and protein levels and we conclude that RKIP contributes
to the monocytic differentiation process via inhibition of the NF[kappa]B
signaling cascade independent from the canonical Ras/Raf/MEK/ERK
pathway.},
issn = {0006-291X},
keywords = {Gene expression, Raf kinase inhibitor protein, Macrophage differentiation,
NF[kappa]B, Scavenger receptors, THP-1 cells},
url = {http://www.sciencedirect.com/science/article/B6WBK-4JB9GR1-D/2/938719435adb27f7cb389b723e7c1638}
}
@ARTICLE{Schuldenfrei2011,
author = {Schuldenfrei, Andrew and Belton, Amy and Kowalski, Jeanne and Talbot,
C Conover and Di Cello, Francescopaolo and Poh, Weijie and Tsai,
Hua-Ling and Shah, Sandeep and Huso, Tait and Huso, David and Resar,
Linda},
title = {HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression
genes during lymphoid tumorigenesis},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {549},
number = {1},
abstract = {BACKGROUND:Although the high mobility group A1 (HMGA1) gene is widely
overexpressed in diverse cancers and portends a poor prognosis in
some tumors, the molecular mechanisms that mediate its role in transformation
have remained elusive. HMGA1 functions as a potent oncogene in cultured
cells and induces aggressive lymphoid tumors in transgenic mice.
Because HMGA1 chromatin remodeling proteins regulate transcription,
HMGA1 is thought to drive malignant transformation by modulating
expression of specific genes. Genome-wide studies to define HMGA1
transcriptional networks during tumorigenesis, however, are lacking.
To define the HMGA1 transcriptome, we analyzed gene expression profiles
in lymphoid cells from HMGA1a transgenic mice at different stages
in tumorigenesis.RESULTS:RNA from lymphoid samples at 2 months (before
tumors develop) and 12 months (after tumors are well-established)
was screened for differential expression of > 20,000 unique genes
by microarray analysis (Affymetrix) using a parametric and nonparametric
approach. Differential expression was confirmed by quantitative RT-PCR
in a subset of genes. Differentially expressed genes were analyzed
for cellular pathways and functions using Ingenuity Pathway Analysis.
Early in tumorigenesis, HMGA1 induced inflammatory pathways with
NFkappaB identified as a major node. In established tumors, HMGA1
induced pathways involved in cell cycle progression, cell-mediated
immune response, and cancer. At both stages in tumorigenesis, HMGA1
induced pathways involved in cellular development, hematopoiesis,
and hematologic development. Gene set enrichment analysis showed
that stem cell and immature T cell genes are enriched in the established
tumors. To determine if these results are relevant to human tumors,
we knocked-down HMGA1 in human T-cell leukemia cells and identified
a subset of genes dysregulated in both the transgenic and human lymphoid
tumors.CONCLUSIONS:We found that HMGA1 induces inflammatory pathways
early in lymphoid tumorigenesis and pathways involved in stem cells,
cell cycle progression, and cancer in established tumors. HMGA1 also
dyregulates genes and pathways involved in stem cells, cellular development
and hematopoiesis at both early and late stages of tumorigenesis.
These results provide insight into HMGA1 function during tumor development
and point to cellular pathways that could serve as therapeutic targets
in lymphoid and other human cancers with aberrant HMGA1 expression.},
doi = {10.1186/1471-2164-12-549},
issn = {1471-2164},
pubmedid = {22053823},
url = {http://www.biomedcentral.com/1471-2164/12/549}
}
@ARTICLE{Schulte2011,
author = {Schulte, Johannes H. and Bachmann, Hagen S. and Brockmeyer, Bent
and DePreter, Katleen and Oberthur, Andre and Ackermann, Sandra and
Kahlert, Yvonne and Pajtler, Kristian and Theissen, Jessica and Westermann,
Frank and Vandesompele, Jo and Speleman, Frank and Berthold, Frank
and Eggert, Angelika and Brors, Benedikt and Hero, Barbara and Schramm,
Alexander and Fischer, Matthias},
title = {High ALK Receptor Tyrosine Kinase Expression Supersedes ALK Mutation
as a Determining Factor of an Unfavorable Phenotype in Primary Neuroblastoma},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {5082-5092},
number = {15},
abstract = {Purpose: Genomic alterations of the anaplastic lymphoma kinase (ALK)
gene have been postulated to contribute to neuroblastoma pathogenesis.
This study aimed to determine the interrelation of ALK mutations,
ALK expression levels, and clinical phenotype in primary neuroblastoma.
Experimental Design: The genomic ALK status and global gene expression
patterns were examined in 263 primary neuroblastomas. Allele-specific
ALK expression was determined by cDNA cloning and sequencing. Associations
of genomic ALK alterations and ALK expression levels with clinical
phenotypes and transcriptomic profiles were compared. Results: Nonsynonymous
point mutations of ALK were detected in 21 of 263 neuroblastomas
(8%). Tumors with ALK mutations exhibited about 2-fold elevated median
ALK mRNA levels in comparison with tumors with wild-type (WT) ALK.
Unexpectedly, the WT allele was preferentially expressed in 12 of
21 mutated tumors. Whereas survival of patients with ALK mutated
tumors was significantly worse as compared with the entire cohort
of WT ALK patients, it was similarly poor in patients with WT ALK
tumors in which ALK expression was as high as in ALK mutated neuroblastomas.
Global gene expression patterns of tumors with ALK mutations or with
high-level WT ALK expression were highly similar, and suggested that
ALK may be involved in cellular proliferation in primary neuroblastoma.
Conclusions: Primary neuroblastomas with mutated ALK exhibit high
ALK expression levels and strongly resemble neuroblastomas with elevated
WT ALK expression levels in both their clinical and molecular phenotypes.
These data suggest that high levels of mutated and WT ALK mediate
similar molecular functions that may contribute to a malignant phenotype
in primary neuroblastoma. Clin Cancer Res; 17(15); 5082-92. (C)2011
AACR.},
doi = {10.1158/1078-0432.CCR-10-2809},
eprint = {http://clincancerres.aacrjournals.org/cgi/reprint/17/15/5082.pdf},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/15/5082}
}
@ARTICLE{Schulte2010,
author = {Schulte, Johannes H. and Marschall, Tobias and Martin, Marcel and
Rosenstiel, Philipp and Mestdagh, Pieter and Schlierf, Stefanie and
Thor, Theresa and Vandesompele, Jo and Eggert, Angelika and Schreiber,
Stefan and Rahmann, Sven and Schramm, Alexander},
title = {Deep sequencing reveals differential expression of microRNAs in favorable
versus unfavorable neuroblastoma},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {5919--5928},
number = {17},
month = sep,
abstract = {Small non-coding RNAs, in particular microRNAs(miRNAs), regulate fine-tuning
of gene expression and can act as oncogenes or tumor suppressor genes.
Differential miRNA expression has been reported to be of functional
relevance for tumor biology. Using next-generation sequencing, the
unbiased and absolute quantification of the small RNA transcriptome
is now feasible. Neuroblastoma(NB) is an embryonal tumor with highly
variable clinical course. We analyzed the small RNA transcriptomes
of five favorable and five unfavorable NBs using SOLiD next-generation
sequencing, generating a total of >188 000 000 reads. MiRNA expression
profiles obtained by deep sequencing correlated well with real-time
PCR data. Cluster analysis differentiated between favorable and unfavorable
NBs, and the miRNA transcriptomes of these two groups were significantly
different. Oncogenic miRNAs of the miR17-92 cluster and the miR-181
family were overexpressed in unfavorable NBs. In contrast, the putative
tumor suppressive microRNAs, miR-542-5p and miR-628, were expressed
in favorable NBs and virtually absent in unfavorable NBs. In-depth
sequence analysis revealed extensive post-transcriptional miRNA editing.
Of 13 identified novel miRNAs, three were further analyzed, and expression
could be confirmed in a cohort of 70 NBs.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/17/5919}
}
@ARTICLE{Schultz2009,
author = {Schultz, Julia and Lorenz, Peter and Ibrahim, Saleh M. and Kundt,
Günther and Gross, Gerd and Kunz, Manfred},
title = {The functional -443T/C osteopontin promoter polymorphism influences
osteopontin gene expression in melanoma cells via binding of c-Myb
transcription factor},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {14--23},
number = {1},
abstract = {Abstract 10.1002/mc.20452.abs In the present report, the possible
role of a recently described functional polymorphism of the osteopontin
(OPN) promoter at position −443 (−443T/C) for OPN expression
in melanoma cells was addressed. As shown by real-time PCR analysis,
melanoma metastases that were homozygous for the −443C allele expressed
significantly higher levels of OPN mRNA compared with those that
were either heterozygous (−443T/C) or homozygous for the −443T
allele. In line with this, immunoblotting showed significantly enhanced
baseline and bFGF-induced OPN protein expression in melanoma cell
lines which were homozygous for the −443C allele, compared with
cell lines with other allelic variants. Similar results were obtained
in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP)
demonstrated binding of c-Myb to the −443 OPN promoter region,
and binding could significantly be enhanced after bFGF stimulation.
Moreover, as shown by electrophoretic mobility shift assays (EMSA),
recombinant DNA-binding domain of c-Myb bound in a sequence-specific
manner to this region. Finally, the role of c-Myb for OPN gene regulation
via binding to the −443 promoter region could be further substantiated
by ectopic overexpression of c-Myb in melanoma cells, using different
reporter gene constructs. Taken together, it is demonstrated that
the −443 promoter region exerts influence on OPN gene expression
in melanoma cells, and differential binding of c-Myb transcription
factor appears to play a major role in this process. These findings
might be a feasible explanation for different OPN expression levels
in metastatic tumors and may also have prognostic and therapeutic
relevance. © 2008 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {carcinogenesis, tumor progression, genetics, gene regulation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20452}
}
@ARTICLE{Schulz2011,
author = {Schulz, Angela and Toedt, Grischa and Zenz, Thorsten and Stilgenbauer,
Stephan and Lichter, Peter and Seiffert, Martina},
title = {Inflammatory cytokines and signaling pathways are associated with
survival of primary chronic lymphocytic leukemia cells in vitro:
a dominant role of CCL2},
journal = {Haematologica},
year = {2011},
volume = {96},
pages = {408--416},
number = {3},
month = mar,
abstract = {BackgroundChronic lymphocytic leukemia cells show prolonged survival
in vivo, but rapidly die by spontaneous apoptosis in vitro, unless
they are co-cultured with stromal cells or non-malignant leukocytes.
The objective of this study was to characterize the survival-inducing
cross-talk of chronic lymphocytic leukemia cells with their microenvironment
to identify novel therapeutic targets. Design and MethodsWe analyzed
and compared microarray-based expression profiles of chronic lymphocytic
leukemia cells before and after three different survival-inducing
culture conditions: (i) stromal cell co-culture, (ii) stromal cell
conditioned medium and (iii) high cell density cultures of unsorted
peripheral blood mononuclear cells. Cytokine antibody arrays were
applied to study the composition of soluble factors present in these
cultures. ResultsThe different survival-supportive culture conditions
induced distinct gene expression changes, the majority of which were
common to all three conditions. Pathway analyses identified - in
addition to known signaling networks in chronic lymphocytic leukemia
- novel pathways, of which Toll-like receptor signaling, nuclear
respiratory factor-2 (NRF2)-mediated oxidative stress response, and
signaling via triggering receptor expressed on myeloid cells-1 (TREM1)
were the most relevant. A high proportion of up-regulated genes were
inflammatory cytokines, of which chemokine (C-C motif) ligand 2 (CCL2)
was shown to be induced in monocytes by the presence of chronic lymphocytic
leukemia cells in vitro. In addition, increased serum levels of this
chemokine were detected in patients with chronic lymphocytic leukemia.
ConclusionsOur data provide several lines of evidence that an inflammatory
microenvironment is induced in survival-supportive cultures of chronic
lymphocytic leukemia cells which might be directly or indirectly
involved in the prolonged survival of the malignant cells.},
comment = {10.3324/haematol.2010.031377},
url = {http://www.haematologica.org/cgi/content/abstract/96/3/408}
}
@ARTICLE{Schulz2010,
author = {Schulz, Martin M. and Buschner, Maximilian G.D. and Leidig, Richard
and Wehner, Heinz-D. and Fritz, Peter and Häbig, Karina and Bonin,
Michael and Schütz, Monika and Shiozawa, Thomas and Wehner, Frank},
title = {A New Approach to the Investigation of Sexual Offenses—Cytoskeleton
Analysis Reveals the Origin of Cells Found on Forensic Swabs*},
journal = {Journal of Forensic Sciences},
year = {2010},
volume = {55},
pages = {492--498},
number = {2},
abstract = {Abstract:  There are forensic inquiries in which an identification
of epithelial cell types would provide important probative evidence.
In cancer diagnosis, this information is yielded by histological
examination of cytokeratin (Ck). Therefore, we tested 19 antibodies
against different Cks (Ck1, Ck2e, Ck4, Ck5-6, Ck7, Ck8, Ck9, CK10,
Ck13, Ck14, Ck15, Ck16, Ck17, Ck18, Ck19, Ck20, Ck903, PanCkAE1_3,
and CAM5-2) on histological sections of epidermis, buccal mucosa,
vaginal mucosa, penis, urogenital tract, and rectum and could identify
two antigens unique to buccal-cell and vaginal-cell (Ck4) and skin
epithelial-cell (Ck10) cytokeratin. Subsequently, we developed an
immunocytological technique for distinguishing swabbed skin and mucosal
cells up to at least 1Â year after sampling. By the detection of
the Ck4 and Ck10 mRNAs in biopsy and laser capture microdissection
collected samples via quantitative real-time polymerase chain reaction,
we were able to confirm our immunological findings. Hence, this study
offers techniques to discriminate between skin and mucosal cells
(buccal and vaginal) in forensic casework.},
issn = {1556-4029},
keywords = {forensic science, immunocytology, cytokeratins, epithelial cells,
sexual offense, DNA, mRNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1556-4029.2009.01071.x}
}
@ARTICLE{Schulz2009,
author = {Schulz, Reiner and McCole, Ruth B. and Woodfine, Kathryn and Wood,
Andrew J. and Chahal, Mandeep and Monk, David and Moore, Gudrun E.
and Oakey, Rebecca J.},
title = {Transcript- and tissue-specific imprinting of a tumour suppressor
gene},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {118--127},
number = {1},
month = jan,
abstract = {The Bladder Cancer-Associated Protein gene (BLCAP; previously BC10)
is a tumour suppressor that limits cell proliferation and stimulates
apoptosis. BLCAP protein or message are downregulated or absent in
a variety of human cancers. In mouse and human, the first intron
of Blcap/BLCAP contains the distinct Neuronatin (Nnat/NNAT) gene.
Nnat is an imprinted gene that is exclusively expressed from the
paternally inherited allele. Previous studies found no evidence for
imprinting of Blcap in mouse or human. Here we show that Blcap is
imprinted in mouse and human brain, but not in other mouse tissues.
Moreover, Blcap produces multiple distinct transcripts that exhibit
reciprocal allele-specific expression in both mouse and human. We
propose that the tissue-specific imprinting of Blcap is due to the
particularly high transcriptional activity of Nnat in brain, as has
been suggested previously for the similarly organized and imprinted
murine Commd1/U2af1-rs1 locus. For Commd1/U2af1-rs1, we show that
it too produces distinct transcript variants with reciprocal allele-specific
expression. The imprinted expression of BLCAP and its interplay with
NNAT at the transcriptional level may be relevant to human carcinogenesis.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/1/118}
}
@ARTICLE{Schulz2006,
author = {Schulz, Reiner and Menheniott, Trevelyan R. and Woodfine, Kathryn
and Wood, Andrew J. and Choi, Jonathan D. and Oakey, Rebecca J.},
title = {Chromosome-wide identification of novel imprinted genes using microarrays
and uniparental disomies},
journal = {Nucleic Acids Res.},
year = {2006},
volume = {34},
pages = {e88--},
number = {12},
month = jul,
abstract = {Genomic imprinting refers to a specialized form of epigenetic gene
regulation whereby the expression of a given allele is dictated by
parental origin. Defining the extent and distribution of imprinting
across genomes will be crucial for understanding the roles played
by imprinting in normal mammalian growth and development. Using mice
carrying uniparental disomies or duplications, microarray screening
and stringent bioinformatics, we have developed the first large-scale
tissue-specific screen for imprinted gene detection. We quantify
the stringency of our methodology and relate it to previous non-tissue-specific
large-scale studies. We report the identification in mouse of four
brain-specific novel paternally expressed transcripts and an additional
three genes that show maternal expression in the placenta. The regions
of conserved linkage in the human genome are associated with the
Prader-Willi Syndrome (PWS) and Beckwith-Wiedemann Syndrome (BWS)
where imprinting is known to be a contributing factor. We conclude
that large-scale systematic analyses of this genre are necessary
for the full impact of genomic imprinting on mammalian gene expression
and phenotype to be elucidated.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/34/12/e88}
}
@ARTICLE{Schulze2009,
author = {Schulze, Holger and Giraud, Gerard and Crain, Jason and Bachmann,
Till T.},
title = {Multiplexed optical pathogen detection with lab-on-a-chip devices},
journal = {J. Biophoton.},
year = {2009},
volume = {2},
pages = {199--211},
number = {4},
abstract = {Abstract 10.1002/jbio.200910009.abs Infectious diseases are still
a main cause of human morbidity and mortality. Advanced diagnostics
is considered to be a key driver to improve the respective therapeutic
outcome. The main factors influencing the impact of diagnostics include:
assay speed, availability, information content, in-vitro diagnostics
and cost, for which molecular assays are providing the most promising
opportunities. Miniaturisation and integration of assay steps into
lab-on-a-chip devices has been described as an appropriate way to
speed up assay time and make assays available onsite at competitive
costs. As meaningful assays for infectious diseases need to include
a whole range of clinical relevant information about the pathogen,
multiplexed functionality is often required for which optical transduction
is particularly well suited. The aim of this review is to assess
existing developments in this field and to give an outlook on future
requirements and solutions. (© 2009 WILEY-VCH Verlag GmbH & Co.
KGaA, Weinheim)},
issn = {1864-0648},
keywords = {infectious diseases, microTAS, in vitro diagnostics, point of care
testing},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/jbio.200910009}
}
@ARTICLE{Schumacher2010,
author = {Schumacher, Marc and Cerella, Claudia and Eifes, Serge and Chateauvieux,
Sébastien and Morceau, Franck and Jaspars, Marcel and Dicato, Mario
and Diederich, Marc},
title = {Heteronemin, a spongean sesterterpene, inhibits TNF[alpha]-induced
NF-[kappa]B activation through proteasome inhibition and induces
apoptotic cell death},
journal = {Biochemical Pharmacology},
year = {2010},
volume = {79},
pages = {610--622},
number = {4},
month = feb,
abstract = {In this study, we investigated the biological effects of heteronemin,
a marine sesterterpene isolated from the sponge Hyrtios sp. on chronic
myelogenous leukemia cells. To gain further insight into the molecular
mechanisms triggered by this compound, we initially performed DNA
microarray profiling and determined which genes respond to heteronemin
stimulation in TNF[alpha]-treated cells and which genes display an
interaction effect between heteronemin and TNF[alpha]. Within the
differentially regulated genes, we found that heteronemin was affecting
cellular processes including cell cycle, apoptosis, mitogen-activated
protein kinases (MAPKs) pathway and the nuclear factor [kappa]B (NF-[kappa]B)
signaling cascade. We confirmed in silico experiments regarding NF-[kappa]B
inhibition by reporter gene analysis, electrophoretic mobility shift
analysis and I-[kappa]B degradation. In order to assess the underlying
molecular mechanisms, we determined that heteronemin inhibits both
trypsin and chymotrypsin-like proteasome activity at an IC50 of 0.4 [mu]M.
Concomitant to the inhibition of the NF-[kappa]B pathway, we also
observed a reduction in cellular viability. Heteronemin induces apoptosis
as shown by annexin V-FITC/propidium iodide-staining, nuclear morphology
analysis, pro-caspase-3, -8 and -9 and poly(ADP-ribose) polymerase
(PARP) cleavage as well as truncation of Bid. Altogether, results
show that this compound has potential as anti-inflammatory and anti-cancer
agent.},
issn = {0006-2952},
keywords = {NF-[kappa]B, Marine natural product, Anti-cancer drug discovery},
url = {http://www.sciencedirect.com/science/article/B6T4P-4XCYJ9Y-2/2/3be3768a0d907c1423497e2b694b7a00}
}
@ARTICLE{Schumacher2011,
author = {Udo Schumacher and Nina Nehmann and Elizabeth Adam and Dhia Mukthar
and Itzchak N. Slotki and Hans-Peter Horny and Marcel J. Flens and
Brigitte Schlegelberger and Doris Steinemann},
title = {MDR-1-overexpression in HT 29 colon cancer cells grown in SCID mice},
journal = {Acta Histochemica},
year = {2011},
pages = { - },
number = {0},
abstract = {The multidrug-resistance 1 (MDR-1) P-glycoprotein (Pgp) is a transmembrane
transporter system, which actively pumps cytotoxic drugs out of the
cell. MDR-1 acquired in vitro differs from MDR-1 acquired in vivo,
but has important consequences on the cellular phenotype and metastatic
behavior. Here we report that the human colonic cancer cell line
HT29 (MDR-1 negative) is more malignant than its MDR-1 overexpressing
variant (HT29 MDR-1 positive). HT29 MDR-1 negative cells produce
undifferentiated signet ring carcinomas when implanted subcutaneously
into SCID mice, while HT29 MDR-1 positive cells form tumors with
tubular structures, but without signet ring cells. Immunohistochemical
proliferation marker analysis revealed that the MDR-1 positive cells
proliferate much more slowly than the MDR-1 negative cells. MDR-1
overexpression results in a less differentiated phenotype at the
cellular level (absence of mucin producing cells) but in a more differentiated
phenotype at the tissue level (tubule formation). In addition, lectin
binding patterns including that of Helix pomatia agglutinin (HPA),
an indicator of metastatic potential, differed between the two cell
lines. HT29 MDR-1 positive cells had less HPA binding sites than
HT29 MDR-1 negative counterparts and metastasized less frequently
in SCID mice. As slow proliferation, low degree of differentiation
and multidrug-resistance is a hallmark of cancer stem cells and all
were present in MDR-1 positive tumors, it is attractive to speculate
that they represent a stem cell rich tumor. As shown by global gene
expression analyses, genes involved, e.g. in cell adhesion, glycosylation
and signal transduction, were deregulated in MDR-1 positive tumors
compared to MDR-negative tumors. Overexpression of E-cadherin and
carcinoembryonic antigen-related cell adhesion molecules 1 (CEACAM1)
may provide clues to the mechanisms responsible for the reduced metastatic
potential of MDR-1 overexpressing tumors. Since drug treatment shifted
the cells towards a less metastatic phenotype in this in vivo model,
it seems conceivable to achieve this using drug treatment also in
a clinical situation.},
doi = {10.1016/j.acthis.2011.11.004},
issn = {0065-1281},
keywords = {Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0065128111001620}
}
@ARTICLE{Schumann2005,
author = {Schumann, Alexandra and Nutten, Sophie and Donnicola, Dominique and
Comelli, Elena M. and Mansourian, Robert and Cherbut, Christine and
Corthesy-Theulaz, Irene and Garcia-Rodenas, Clara},
title = {Neonatal antibiotic treatment alters gastrointestinal tract developmental
gene expression and intestinal barrier transcriptome},
journal = {Physiol Genomics},
year = {2005},
volume = {23},
pages = {235--245},
number = {2},
month = oct,
abstract = {The postnatal maturation of the gut, partially modulated by bacterial
colonization, ends up in the establishment of an efficient barrier
to luminal antigens and bacteria. The use of broad-spectrum antibiotics
in pediatric practices alters the gut bacterial colonization and,
consequently, may impair the maturation of the gut barrier function.
To test this hypothesis, suckling Sprague-Dawley rats received a
daily intragastric gavage of antibiotic (Clamoxyl; an amoxicillin-based
commercial preparation) or saline solution from postnatal day 7 (d7)
until d17 or d21. Luminal microbiota composition and global gene
expression profile were analyzed on samples from small intestine
and colon of each group. The treatment with Clamoxyl resulted in
the almost-complete eradication of Lactobacillus in the whole intestine
and in a drastic reduction of colonic total aerobic and anaerobic
bacteria, in particular Enterobacteriacae and Enterococcus. The global
gene expression analysis revealed that Clamoxyl affects the maturation
process of 249 and 149 Affymetrix probe sets in the proximal and
distal small intestine, respectively, and 163 probe sets in the colon.
The expression of genes coding for Paneth cell products (defensins,
matrilysin, and phospholipase A2) was significantly downregulated
by the Clamoxyl treatment. A significant downregulation of major
histocompatibility complex (MHC) class Ib and II genes, involved
in antigen presentation, was also observed. Conversely, mast cell
proteases expression was upregulated. These results suggest that
early treatment with a large-spectrum antibiotic deeply affects the
gut barrier function at the suckling-weaning interface, a period
during which the gut is challenged by an array of novel food-borne
antigens.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/23/2/235}
}
@ARTICLE{Schumann2011,
author = {Schumann, Gunter and Coin, Lachlan J. and Lourdusamy, Anbarasu and
Charoen, Pimphen and Berger, Karen H. and Stacey, David and Desrivieres,
Sylvane and Aliev, Fazil A. and Khan, Anokhi A. and Amin, Najaf and
Aulchenko, Yurii S. and Bakalkin, Georgy and Bakker, Stephan J. and
Balkau, Beverley and Beulens, Joline W. and Bilbao, Ainhoa and de
Boer, Rudolf A. and Beury, Delphine and Bots, Michiel L. and Breetvelt,
Elemi J. and Cauchi, Stephane and Cavalcanti-Proenca, Christine and
Chambers, John C. and Clarke, Toni-Kim and Dahmen, Norbert and de
Geus, Eco J. and Dick, Danielle and Ducci, Francesca and Easton,
Alanna and Edenberg, Howard J. and Esko, Tonu and Fernandez-Medarde,
Alberto and Foroud, Tatiana and Freimer, Nelson B. and Girault, Jean-Antoine
and Grobbee, Diederick E. and Guarrera, Simonetta and Gudbjartsson,
Daniel F. and Hartikainen, Anna-Liisa and Heath, Andrew C. and Hesselbrock,
Victor and Hofman, Albert and Hottenga, Jouke-Jan and Isohanni, Matti
K. and Kaprio, Jaakko and Khaw, Kay-Tee and Kuehnel, Brigitte and
Laitinen, Jaana and Lobbens, Stephane and Luan, Jian'an and Mangino,
Massimo and Maroteaux, Matthieu and Matullo, Giuseppe and McCarthy,
Mark I. and Mueller, Christian and Navis, Gerjan and Numans, Mattijs
E. and Nunez, Alejandro and Nyholt, Dale R. and Onland-Moret, Charlotte
N. and Oostra, Ben A. and O'Reilly, Paul F. and Palkovits, Miklos
and Penninx, Brenda W. and Polidoro, Silvia and Pouta, Anneli and
Prokopenko, Inga and Ricceri, Fulvio and Santos, Eugenio and Smit,
Johannes H. and Soranzo, Nicole and Song, Kijoung and Sovio, Ulla
and Stumvoll, Michael and Surakk, Ida and Thorgeirsson, Thorgeir
E. and Thorsteinsdottir, Unnur and Troakes, Claire and Tyrfingsson,
Thorarinn and Tonjes, Anke and Uiterwaal, Cuno S. and Uitterlinden,
Andre G. and van der Harst, Pim and van der Schouw, Yvonne T. and
Staehlin, Oliver and Vogelzangs, Nicole and Vollenweider, Peter and
Waeber, Gerard and Wareham, Nicholas J. and Waterworth, Dawn M. and
Whitfield, John B. and Wichmann, Erich H. and Willemsen, Gonneke
and Witteman, Jacqueline C. and Yuan, Xin and Zhai, Guangju and Zhao,
Jing H. and Zhang, Weihua and Martin, Nicholas G. and Metspalu, Andres
and Doering, Angela and Scott, James and Spector, Tim D. and Loos,
Ruth J. and Boomsma, Dorret I. and Mooser, Vincent and Peltonen,
Leena and Stefansson, Kari and van Duijn, Cornelia M. and Vineis,
Paolo and Sommer, Wolfgang H. and Kooner, Jaspal S. and Spanagel,
Rainer and Heberlein, Ulrike A. and Jarvelin, Marjo-Riitta and Elliott,
Paul},
title = {Genome-wide association and genetic functional studies identify autism
susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol
consumption},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {7119-7124},
number = {17},
abstract = {Alcohol consumption is a moderately heritable trait, but the genetic
basis in humans is largely unknown, despite its clinical and societal
importance. We report a genome-wide association study meta-analysis
of [~]2.5 million directly genotyped or imputed SNPs with alcohol
consumption (gram per day per kilogram body weight) among 12 population-based
samples of European ancestry, comprising 26,316 individuals, with
replication genotyping in an additional 21,185 individuals. SNP rs6943555
in autism susceptibility candidate 2 gene (AUTS2) was associated
with alcohol consumption at genome-wide significance (P = 4 x 10-8
to P = 4 x 10-9). We found a genotype-specific expression of AUTS2
in 96 human prefrontal cortex samples (P = 0.026) and significant
(P < 0.017) differences in expression of AUTS2 in whole-brain extracts
of mice selected for differences in voluntary alcohol consumption.
Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity
in Drosophila (P < 0.001). Our finding of a regulator of alcohol
consumption adds knowledge to our understanding of genetic mechanisms
influencing alcohol drinking behavior.},
doi = {10.1073/pnas.1017288108},
eprint = {http://www.pnas.org/cgi/reprint/108/17/7119.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/17/7119}
}
@ARTICLE{Schurko2009,
author = {Schurko, Andrew and Logsdon, John and Eads, Brian},
title = {Meiosis genes in Daphnia pulex and the role of parthenogenesis in
genome evolution},
journal = {BMC Evolutionary Biology},
year = {2009},
volume = {9},
pages = {78},
number = {1},
abstract = {BACKGROUND:Thousands of parthenogenetic animal species have been described
and cytogenetic manifestations of this reproductive mode are well
known. However, little is understood about the molecular determinants
of parthenogenesis. The Daphnia pulex genome must contain the molecular
machinery for different reproductive modes: sexual (both male and
female meiosis) and parthenogenetic (which is either cyclical or
obligate). This feature makes D. pulex an ideal model to investigate
the genetic basis of parthenogenesis and its consequences for gene
and genome evolution. Here we describe the inventory of meiotic genes
and their expression patterns during meiotic and parthenogenetic
reproduction to help address whether parthenogenesis uses existing
meiotic and mitotic machinery, or whether novel processes may be
involved.RESULTS:We report an inventory of 130 homologs representing
over 40 genes encoding proteins with diverse roles in meiotic processes
in the genome of D. pulex. Many genes involved in cell cycle regulation
and sister chromatid cohesion are characterized by expansions in
copy number. In contrast, most genes involved in DNA replication
and homologous recombination are present as single copies. Notably,
RECQ2 (which suppresses homologous recombination) is present in multiple
copies while DMC1 is the only gene in our inventory that is absent
in the Daphnia genome. Expression patterns for 44 gene copies were
similar during meiosis versus parthenogenesis, although several genes
displayed marked differences in expression level in germline and
somatic tissues.CONCLUSION:We propose that expansions in meiotic
gene families in D. pulex may be associated with parthenogenesis.
Taking into account our findings, we provide a mechanistic model
of parthenogenesis, highlighting steps that must differ from meiosis
including sister chromatid cohesion and kinetochore attachment.},
doi = {10.1186/1471-2148-9-78},
issn = {1471-2148},
pubmedid = {19383157},
url = {http://www.biomedcentral.com/1471-2148/9/78}
}
@ARTICLE{Schurman2009,
author = {Schurman, Shepherd H. and Hedayati, Mohammad and Wang, ZhengMing
and Singh, Dharmendra K. and Speina, Elzbieta and Zhang, Yongqing
and Becker, Kevin and Macris, Margaret and Sung, Patrick and Wilson,
David M., III and Croteau, Deborah L. and Bohr, Vilhelm A.},
title = {Direct and indirect roles of RECQL4 in modulating base excision repair
capacity},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {3470--3483},
number = {18},
month = sep,
abstract = {RECQL4 is a human RecQ helicase which is mutated in approximately
two-thirds of individuals with Rothmund-Thomson syndrome (RTS), a
disease characterized at the cellular level by chromosomal instability.
BLM and WRN are also human RecQ helicases, which are mutated in Bloom
and Werner's syndrome, respectively, and associated with chromosomal
instability as well as premature aging. Here we show that primary
RTS and RECQL4 siRNA knockdown human fibroblasts accumulate more
H2O2-induced DNA strand breaks than control cells, suggesting that
RECQL4 may stimulate repair of H2O2-induced DNA damage. RTS primary
fibroblasts also accumulate more XRCC1 foci than control cells in
response to endogenous or induced oxidative stress and have a high
basal level of endogenous formamidopyrimidines. In cells treated
with H2O2, RECQL4 co-localizes with APE1, and FEN1, key participants
in base excision repair. Biochemical experiments indicate that RECQL4
specifically stimulates the apurinic endonuclease activity of APE1,
the DNA strand displacement activity of DNA polymerase {beta}, and
incision of a 1- or 10-nucleotide flap DNA substrate by Flap Endonuclease
I. Additionally, RTS cells display an upregulation of BER pathway
genes and fail to respond like normal cells to oxidative stress.
The data herein support a model in which RECQL4 regulates both directly
and indirectly base excision repair capacity.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/18/3470}
}
@ARTICLE{Schuurhof2010,
author = {Schuurhof, Annemieke and Bont, Louis and Pennings, Jeroen L. A. and
Hodemaekers, Hennie M. and Wester, Piet W. and Buisman, Annemarie
and de Rond, Lia C. G. H. and Widjojoatmodjo, Myra N. and Luytjes,
Willem and Kimpen, Jan L. L. and Janssen, Riny},
title = {Gene Expression Differences in Lungs of Mice during Secondary Immune
Responses to Respiratory Syncytial Virus Infection},
journal = {J. Virol.},
year = {2010},
volume = {84},
pages = {9584--9594},
number = {18},
month = sep,
abstract = {Vaccine-induced immunity has been shown to alter the course of a respiratory
syncytial virus (RSV) infection both in murine models and in humans.
To elucidate which mechanisms underlie the effect of vaccine-induced
immunity on the course of RSV infection, transcription profiles in
the lungs of RSV-infected mice were examined by microarray analysis.
Three models were used: RSV reinfection as a model for natural immunity,
RSV challenge after formalin-inactivated RSV vaccination as a model
for vaccine-enhanced disease, and RSV challenge following vaccination
with recombinant RSV virus lacking the G gene ({Delta}G-RSV) as a
model for vaccine-induced immunity. Gene transcription profiles,
histopathology, and viral loads were analyzed at 1, 2, and 5 days
after RSV challenge. On the first 2 days after challenge, all mice
displayed an expression pattern in the lung similar of that found
in primary infection, showing a strong innate immune response. On
day 5 after RSV reinfection or after challenge following {Delta}G-RSV
vaccination, the innate immune response was waning. In contrast,
in mice with vaccine-enhanced disease, the innate immune response
5 days after RSV challenge was still present even though viral replication
was diminished. In addition, only in this group was Th2 gene expression
induced. These findings support a hypothesis that vaccine-enhanced
disease is mediated by prolonged innate immune responses and Th2
polarization in the absence of viral replication.},
url = {http://jvi.asm.org/cgi/content/abstract/84/18/9584}
}
@ARTICLE{Schuurmans2008,
author = {Schuurmans, J. Merijn and Boorsma, André and Lascaris, Romeo and
Hellingwerf, Klaas J. and Teixeira de Mattos, M. Joost},
title = {Physiological and transcriptional characterization of Saccharomyces
cerevisiae strains with modified expression of catabolic regulators},
journal = {FEMS Yeast Research},
year = {2008},
volume = {8},
pages = {26--34},
number = {1},
abstract = {Abstract A comparative physiological and transcriptional study is
presented on wild-type Saccharomyces cerevisiae and mutants with
altered levels of catabolic regulators: hxk2Δ lacking hexokinase2,
HAP4↑ overproducing hap4p and hxk2ΔHAP4↑. Relative to the wild-type,
HAP4↑ showed the same growth rate with some increased yield on
glucose, and hxk2Δ grew 28% slower but with a dramatically improved
yield. Hxk2ΔHAP4↑ grew 14% slower but showed fully oxidative growth.
A higher yield correlated with increased respiration. For both hxk2Δ
strains, glucose repression was suppressed (upregulation of high-affinity
sugar transporters, invertase and oxidative phosphorylation). T-profiler
analysis showed that genes under control of the hap2/3/4/5-binding
motif were significantly altered in expression in all strains. HAP4
overexpression, directly or in hxk2 knockouts, led to repression
of the genes containing the Zap1p motif including ZAP1 itself, indicating
altered zinc metabolism. Whereas HAP4 overexpression resulted in
a shift towards oxidative metabolism only, deletion of HXK2 resulted
in a strain that, in addition to being oxidative, almost completely
lacked the ability to sense glucose. As the double mutant had an
energy efficiency close to the maximum even with excess glucose and
was derepressed to a larger extent and over a broader range, the
functioning of the two regulators is in general considered to be
additive.},
issn = {1567-1364},
keywords = {hap4p, hxk2p, glucose repression, yield, fermento–respirative metabolism,
T-profiler},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1567-1364.2007.00309.x}
}
@ARTICLE{Schuurmans2008a,
author = {Schuurmans, Jasper Merijn and Rossell, Sergio L. and Van Tuijl, Arjen
and Bakker, Barbara M. and Hellingwerf, Klaas J. and Teixeira de
Mattos, Maarten Joost},
title = {Effect of hxk2 deletion and HAP4 overexpression on fermentative capacity
in Saccharomyces cerevisiae},
journal = {FEMS Yeast Research},
year = {2008},
volume = {8},
pages = {195--203},
number = {2},
abstract = {Abstract To describe the fermentative potential of a yeast cell, the
fermentative capacity (FC) has been defined as the specific rate
of ethanol and CO2 production under anaerobic conditions. The effect
of growth rate on FC of glucose-limited grown Saccharomyces cerevisiae
strains with altered expression of two major glycolytic regulators,
Hap4p and Hxk2p, was compared with their parent strain. Whereas overproduction
of Hap4p behaved similar to the wild-type strain, deletion of hxk2
resulted in a very different FC profile. Most importantly, with maltose
as the carbon and energy source, the latter strain expressed an FC
twofold that of the wild type. Further analysis at the level of gene
expression showed large changes in ADH2 transcripts and to a lesser
extent in hexose transporters and genes involved in the glyoxylate
cycle. With respect to primary glucose metabolism, a shift in the
type of hexose transport to one with high affinity was induced. In
accordance with the phenotype of the mutant strain, the maltose transporter
was constitutively expressed under glucose-limited conditions and
synthesis increased in the presence of maltose.},
issn = {1567-1364},
keywords = {fermentative capacity, maltose, glycolysis, regulation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1567-1364.2007.00319.x}
}
@ARTICLE{Schwaiger2010,
author = {Schwaiger, Rita and Schwarz, Christoph and Furtwängler, Katarina
and Tarasov, Valery and Wende, Andy and Oesterhelt, Dieter},
title = {Transcriptional control by two leucine-responsive regulatory proteins
in Halobacterium salinarum R1},
journal = {BMC Molecular Biology},
year = {2010},
volume = {11},
pages = {40},
number = {1},
abstract = {BACKGROUND:Archaea combine bacterial-as well as eukaryotic-like features
to regulate cellular processes. Halobacterium salinarum R1 encodes
eight leucine-responsive regulatory protein (Lrp)-homologues. The
function of two of them, Irp (OE3923F) and lrpA1 (OE2621R), were
analyzed by gene deletion and overexpression, including genome scale
impacts using microarrays.RESULTS:It was shown that Lrp affects the
transcription of multiple target genes, including those encoding
enzymes involved in amino acid synthesis, central metabolism, transport
processes and other regulators of transcription. In contrast, LrpA1
regulates transcription in a more specific manner. The aspB3 gene,
coding for an aspartate transaminase, was repressed by LrpA1 in the
presence of L-aspartate. Analytical DNA-affinity chromatography was
adapted to high salt, and demonstrated binding of LrpA1 to its own
promoter, as well as L-aspartate dependent binding to the aspB3 promoter.CONCLUSION:The
gene expression profiles of two archaeal Lrp-homologues report in
detail their role in H. salinarum R1. LrpA1 and Lrp show similar
functions to those already described in bacteria, but in addition
they play a key role in regulatory networks, such as controlling
the transcription of other regulators. In a more detailed analysis
ligand dependent binding of LrpA1 was demonstrated to its target
gene aspB3.},
doi = {10.1186/1471-2199-11-40},
issn = {1471-2199},
pubmedid = {20509863},
url = {http://www.biomedcentral.com/1471-2199/11/40}
}
@ARTICLE{Schwalbach2010,
author = {Schwalbach, M. S. and Tripp, H. J. and Steindler, L. and Smith, D.
P. and Giovannoni, S. J.},
title = {The presence of the glycolysis operon in SAR11 genomes is positively
correlated with ocean productivity},
journal = {Environmental Microbiology},
year = {2010},
volume = {12},
pages = {490--500},
number = {2},
abstract = {Summary Bacteria in the SAR11 clade are highly abundant in marine
surface waters, but currently little is known about the carbon compounds
that support these large heterotrophic populations. To better understand
the carbon requirements of these organisms, we conducted a multiphasic
exploration of carbohydrate utilization among SAR11 isolates from
the Northeast Pacific Ocean and the Sargasso Sea. A comparison of
three SAR11 genomes showed they all lacked a recognizable PTS system,
the oxidative portion of the pentose phosphate shunt (zwf-, pgl-),
genes for the Embden–Meyerhoff–Parnas (pfk-, pyk-) and Entner–Doudoroff
(eda-) pathways of glycolysis. Strain HTCC7211, isolated from an
ocean gyre, was missing other glycolysis genes as well. Growth assays,
radioisotopes, metagenomics and microarrays were used to test the
hypothesis that these isolates might be limited in their abilities
to transport and oxidize exogenous carbohydrates. Galactose, fucose,
rhamnose, arabinose, ribose and mannose could not serve as carbon
sources for the isolates tested. However, differences in glucose
utilization were detected between coastal and ocean gyre isolates,
with the coastal isolates capable of transporting, incorporating
and oxidizing glucose while the open ocean isolate could not. Subsequent
microarray analysis of a coastal isolate suggested that an operon
encoding a variant of the Entner–Doudoroff pathway is likely responsible
for the observed differences in glucose utilization. Metagenomic
analysis indicated this operon is more commonly found in coastal
environments and is positively correlated with chlorophyll a concentrations.
Our results indicated that glycolysis is a variable metabolic property
of SAR11 metabolism and suggest that glycolytic SAR11 are more common
in productive marine environments.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2009.02092.x}
}
@ARTICLE{Schwalm2008,
author = {Schwalm, Kurt and Stevens, Junko F. and Jiang, Zeyu and Schuyler,
Mark R. and Schrader, Ron and Randell, Scott H. and Green, Francis
H. Y. and Tesfaigzi, Yohannes},
title = {Expression of the proapoptotic protein Bax is reduced in bronchial
mucous cells of asthmatic subjects},
journal = {Am J Physiol Lung Cell Mol Physiol},
year = {2008},
volume = {294},
pages = {L1102--1109},
number = {6},
month = jun,
abstract = {The present studies were designed to determine whether our findings
in mice showing that the Bcl-2-associated protein X (Bax), which
plays a role in the resolution of allergen-induced mucous cell metaplasia,
can be applied to asthma in humans. Immunostaining of autopsy tissues
from mild and severe asthmatic subjects showed a significant reduction
in the percentage of Bax-positive mucous cells compared with those
from nonasthmatic controls. To exclude the possibility that postmortem
changes may have affected Bax expression, Bax mRNA levels in airway
epithelial cells obtained from nonsmoking asthmatic subjects were
compared with those from nonasthmatic controls. Because the number
of cells obtained by bronchial brushings is limited, we developed
a robust preamplification procedure of cDNA before quantitative real-time
PCR to allow detection of 100 gene targets from limited sample size,
even when it was prepared from partially degraded RNA. cDNA was prepared
by reverse transcription from RNA isolated from bronchial epithelial
cells obtained by bronchial brushings from well-characterized subjects
without lung disease and from subjects with mild asthma. Quantitative
analysis showed that Bax mRNA levels were significantly reduced in
samples obtained from asthma patients compared with nonasthma controls.
Furthermore, Bax mRNA levels were reduced when primary airway epithelial
cells from 10 individuals were treated in culture with the T helper
2 cytokine IL-13. These studies show that Bax expression is reduced
in airway epithelial cells of even mild asthmatic subjects and suggest
that restoring Bax expression may provide a clinical approach for
restoring the normal numbers of epithelial cells and reduced mucous
hypersecretion in asthma.},
url = {http://ajplung.physiology.org/cgi/content/abstract/294/6/L1102}
}
@ARTICLE{Schwanke2006,
author = {Schwanke, Kristin and Wunderlich, Stephanie and Reppel, Michael and
Winkler, Monica E. and Matzkies, Matthias and Groos, Stephanie and
Itskovitz-Eldor, Joseph and Simon, André R. and Hescheler, Jürgen
and Haverich, Axel and Martin, Ulrich},
title = {Generation and Characterization of Functional Cardiomyocytes from
Rhesus Monkey Embryonic Stem Cells},
journal = {STEM CELLS},
year = {2006},
volume = {24},
pages = {1423--1432},
number = {6},
abstract = {Abstract 10.1634/stemcells.2005-0380.abs Embryonic stem cells (ESCs)
from mice and humans (hESCs) have been shown to be able to efficiently
differentiate toward cardiomyocytes (CMs). Because murine ESCs and
hESCs do not allow for establishment of pre-clinical allogeneic transplantation
models, the aim of our study was to generate functional CMs from
rhesus monkey ESCs (rESCs). Although formation of ectodermal and
neuronal/glial cells appears to be the default pathway of the rESC
line R366.4, we were able to change this commitment and to direct
generation of endodermal/mesodermal cells and further differentiation
toward CMs. Differentiation of rESCs resulted in an average of 18%
of spontaneously contracting embryoid bodies (EBs) from rESCs. Semiquantitative
reverse transcription-polymerase chain reaction analyses demonstrated
expression of marker genes typical for endoderm, mesoderm, cardiac
mesoderm, and CMs, including brachyury, goosecoid, Tbx-5, Tbx-20,
Mesp1, Nkx2.5, GATA-4, FOG-2, Mlc2a, MLC2v, ANF, and α-MHC in rESC-derived
CMs. Immunohistological and ultrastructural studies showed expression
of CM-typical proteins, including sarcomeric actinin, troponin T,
titin, connexin 43, and cross-striated muscle fibrils. Electrophysiological
studies by means of multielectrode arrays revealed evidence of functionality,
electrical coupling, and β-adrenergic signaling of the generated
CMs. This is the first study demonstrating generation of functional
CMs derived from rESCs. In contrast to hESCs, rESCs allow for establishment
of pre-clinical allogeneic transplantation models. Moreover, rESC-derived
CMs represent a cell source for the development of high-throughput
assays for cardiac safety pharmacology.},
issn = {1549-4918},
keywords = {Embryonic stem cells, Differentiation, Cardiomyocytes, Primates},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2005-0380}
}
@ARTICLE{Schwartz2007,
author = {Schwartz, Donald R. and Moin, Kamiar and Yao, Bin and Matrisian,
Lynn M. and Coussens, Lisa M. and Bugge, Thomas H. and Fingleton,
Barbara and Acuff, Heath B. and Sinnamon, Mark and Nassar, Hind and
Platts, Adrian E. and Krawetz, Stephen A. and Linebaugh, Bruce E.
and Sloane, Bonnie F.},
title = {Hu/Mu ProtIn Oligonucleotide Microarray: Dual-Species Array for Profiling
Protease and Protease Inhibitor Gene Expression in Tumors and Their
Microenvironment},
journal = {Mol. Cancer Res.},
year = {2007},
volume = {5},
pages = {443--454},
number = {5},
month = may,
abstract = {Proteolysis is a critical regulatory mechanism for a wide variety
of physiologic and pathologic processes. To assist in the identification
of proteases, their endogenous inhibitors, and proteins that interact
with proteases or proteolytic pathways in biological tissues, a dual-species
oligonucleotide microarray has been developed in conjunction with
Affymetrix. The Hu/Mu ProtIn microarray contains 516 and 456 probe
sets that survey human and mouse genes of interest (proteases, protease
inhibitors, or interactors), respectively. To investigate the performance
of the array, gene expression profiles were analyzed in pure mouse
and human samples (reference RNA; normal and tumor cell lines/tissues)
and orthotopically implanted xenografts of human A549 lung and MDA-MB-231
breast carcinomas. Relative gene expression and "present-call" P
values were determined for each probe set using dChip and MAS5 software,
respectively. Despite the high level of sequence identity of mouse
and human protease/inhibitor orthologues and the theoretical potential
for cross-hybridization of some of the probes, >95% of the "present
calls" (P < 0.01) resulted from same-species hybridizations (e.g.,
human transcripts to human probe sets). To further assess the performance
of the microarray, differential gene expression and false discovery
rate analyses were carried out on human or mouse sample groups, and
data processing methods to optimize performance of the mouse and
human probe sets were identified. The Hu/Mu ProtIn microarray is
a valuable discovery tool for the identification of components of
human and murine proteolytic pathways in health and disease and has
particular utility in the determination of cellular origins of proteases
and protease inhibitors in xenograft models of human cancer. (Mol
Cancer Res 2007;5(5):443-54)},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/5/5/443}
}
@ARTICLE{Schwartz2009,
author = {Schwartz, Edward and Voigt, Birgit and Zühlke, Daniela and Pohlmann,
Anne and Lenz, Oliver and Albrecht, Dirk and Schwarze, Alexander
and Kohlmann, Yvonne and Krause, Cornelia and Hecker, Michael and
Friedrich, Bärbel},
title = {A proteomic view of the facultatively chemolithoautotrophic lifestyle
of Ralstonia eutropha H16},
journal = {Proteomics},
year = {2009},
volume = {9},
pages = {5132--5142},
number = {22},
abstract = {Abstract 10.1002/pmic.200900333.abs Ralstonia eutropha H16 is an H2-oxidizing,
facultative chemolithoautotroph. Using 2-DE in conjunction with peptide
mass spectrometry we have cataloged the soluble proteins of this
bacterium during growth on different substrates: (i) H2 and CO2,
(ii) succinate and (iii) glycerol. The first and second conditions
represent purely lithoautotrophic and purely organoheterotrophic
nutrition, respectively. The third growth regime permits formation
of the H2-oxidizing and CO2-fixing systems concomitant to utilization
of an organic substrate, thus enabling mixotrophic growth. The latter
type of nutrition is probably the relevant one with respect to the
situation faced by the organism in its natural habitats, i.e. soil
and mud. Aside from the hydrogenase and Calvin-cycle enzymes, the
protein inventories of the H2-CO2- and succinate-grown cells did
not reveal major qualitative differences. The protein complement
of the glycerol-grown cells resembled that of the lithoautotrophic
cells. Phosphoenolpyruvate (PEP) carboxykinase was present under
all three growth conditions, whereas PEP carboxylase was not detectable,
supporting earlier findings that PEP carboxykinase is alone responsible
for the anaplerotic production of oxaloacetate from PEP. The elevated
levels of oxidative stress proteins in the glycerol-grown cells point
to a significant challenge by ROS under these conditions. The results
reported here are in agreement with earlier physiological and enzymological
studies indicating that R. eutropha H16 has a heterotrophic core
metabolism onto which the functions of lithoautotrophy have been
grafted.},
issn = {1615-9861},
keywords = {Autotrophy, Hydrogenase, Lithotrophy, Microbiology, Oxidative stress,
Phosphoenolpyruvate-pyruvate-oxaloacetate node},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200900333}
}
@ARTICLE{Schwartz2005,
author = {Schwartz, Philip H. and Nethercott, Hubert and Kirov, Ivan I. and
Ziaeian, Boback and Young, Michael J. and Klassen, Henry},
title = {Expression of Neurodevelopmental Markers by Cultured Porcine Neural
Precursor Cells},
journal = {STEM CELLS},
year = {2005},
volume = {23},
pages = {1286--1294},
number = {9},
abstract = {Abstract 10.1634/stemcells.2004-0306.abs Despite the increasing importance
of the pig as a large animal model, little is known about porcine
neural precursor cells. To evaluate the markers expressed by these
cells, brains were dissected from 60-day fetuses, enzymatically dissociated,
and grown in the presence of epidermal growth factor, basic fibroblast
growth factor, and platelet-derived growth factor. Porcine neural
precursors could be grown as suspended spheres or adherent monolayers,
depending on culture conditions. Expanded populations were banked
or harvested for analysis using reverse transcription–polymerase
chain reaction (RT-PCR), immunocytochemistry, microarrays, and flow
cytometry, and results compared with data from analogous human forebrain
progenitor cells. Cultured porcine neural precursors widely expressed
neural cell adhesion molecule (NCAM), polysialic acid (PSA)–NCAM,
vimentin, Ki-67, and Sox2. Minority subpopulations of cells expressed
doublecortin, β-III tubulin, synapsin I, glial fibrillary acidic
protein (GFAP), and aquaporin 4 (AQP4) consistent with increased
lineage restriction. A human microarray detected porcine transcripts
for nogoA (RTN4) and stromal cell–derived factor 1 (SDF1), possibly
cyclin D2 and Pbx1, but not CD133, Ki-67, nestin, or nucleostemin.
Subsequent RT-PCR showed pig forebrain precursors to be positive
for cyclin D2, nucleostemin, nogoA, Pbx1, vimentin, and a faint band
for SDF1, whereas no signal was detected for CD133, fatty acid binding
protein 7 (FABP7), or Ki-67. Human forebrain progenitor cells were
positive for all the genes mentioned. This study shows that porcine
neural precursors share many characteristics with their human counterparts
and, thus, may be useful in porcine cell transplantation studies
potentially leading to the application of this strategy in the setting
of nervous system disease and injury.},
issn = {1549-4918},
keywords = {Neural stem cells, Progenitor cells, Brain, Nestin, Sox2, Pig, Human},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2004-0306}
}
@ARTICLE{Schwartz2010,
author = {Schwartz, Tonia and Tae, Hongseok and Yang, Youngik and Mockaitis,
Keithanne and Van Hemert, John and Proulx, Stephen and Choi, Jeong-Hyeon
and Bronikowski, Anne},
title = {A garter snake transcriptome: pyrosequencing, de novo assembly, and
sex-specific differences},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {694},
number = {1},
abstract = {BACKGROUND:The reptiles, characterized by both diversity and unique
evolutionary adaptations, provide a comprehensive system for comparative
studies of metabolism, physiology, and development. However, molecular
resources for ectothermic reptiles are severely limited, hampering
our ability to study the genetic basis for many evolutionarily important
traits such as metabolic plasticity, extreme longevity, limblessness,
venom, and freeze tolerance. Here we use massively parallel sequencing
(454 GS-FLX Titanium) to generate a transcriptome of the western
terrestrial garter snake (Thamnophis elegans) with two goals in mind.
First, we develop a molecular resource for an ectothermic reptile;
and second, we use these sex-specific transcriptomes to identify
differences in the presence of expressed transcripts and potential
genes of evolutionary interest.RESULTS:Using sex-specific pools of
RNA (one pool for females, one pool for males) representing 7 tissue
types and 35 diverse individuals, we produced 1.24 million sequence
reads, which averaged 366 bp in length after cleaning. Assembly of
the cleaned reads from both sexes with NEWBLER and MIRA resulted
in 96,379 contigs containing 87% of the cleaned reads. Over 34% of
these contigs and 13% of the singletons were annotated based on homology
to previously identified proteins. From these homology assignments,
additional clustering, and ORF predictions, we estimate that this
transcriptome contains ~13,000 unique genes that were previously
identified in other species and over 66,000 transcripts from unidentified
protein-coding genes. Furthermore, we use a graph-clustering method
to identify contigs linked by NEWBLER-split reads that represent
divergent alleles, gene duplications, and alternatively spliced transcripts.
Beyond gene identification, we identified 95,295 SNPs and 31,651
INDELs. From these sex-specific transcriptomes, we identified 190
genes that were only present in the mRNA sequenced from one of the
sexes (84 female-specific, 106 male-specific), and many highly variable
genes of evolutionary interest.CONCLUSIONS:This is the first large-scale,
multi-organ transcriptome for an ectothermic reptile. This resource
provides the most comprehensive set of EST sequences available for
an individual ectothermic reptile species, increasing the number
of snake ESTs 50-fold. We have identified genes that appear to be
under evolutionary selection and those that are sex-specific. This
resource will assist studies on gene expression and comparative genomics,
and will facilitate the study of evolutionarily important traits
at the molecular level.},
doi = {10.1186/1471-2164-11-694},
issn = {1471-2164},
pubmedid = {21138572},
url = {http://www.biomedcentral.com/1471-2164/11/694}
}
@ARTICLE{Schwarz2011,
author = {Schwarz, B. and Ertl, R. and Zimmer, S. and Netzmann, Y. and Klein,
D. and Schwendenwein, I. and Hoven, R. V. D.},
title = {Estimated prevalence of the GYS-1 mutation in healthy Austrian Haflingers},
journal = {Vet Rec},
year = {2011},
volume = {169},
pages = {583},
number = {22},
abstract = {The aim of this study was to determine the occurrence and frequency
of a mutation in the gene coding for skeletal muscle glycogen synthase
type 1 (GYS-1), which is the cause of equine polysaccharide storage
myopathy (PSSM) type 1 in a population of 50 Haflingers. GYS-1 genotyping
of 50 Haflingers was performed with a validated restriction fragment
length polymorphism (RFLP) assay. The second aim was to compare resting
and post-exercise muscle enzyme activities as well as parameters
of glucose metabolism in blood between horses with and without the
mutation. Nine of the 50 Haflingers were identified to be heterozygous
for the mutation (HR). None was homozygous (HH). The estimated HR
prevalence was 18 per cent in this herd. Mean aspartate aminotransferase
(AST) activity at rest and mean creatine kinase and AST activity
after exercise were significantly higher in HR compared with RR (homozygote
normal) horses. No significant differences could be found in the
other parameters.},
doi = {10.1136/vr.d5438},
eprint = {http://veterinaryrecord.bmj.com/cgi/reprint/169/22/583.pdf},
url = {http://veterinaryrecord.bmj.com/cgi/content/abstract/169/22/583}
}
@ARTICLE{Schwarz2008,
author = {Schwarz, Jodi and Brokstein, Peter and Voolstra, Christian and Terry,
Astrid and Miller, David and Szmant, Alina and Coffroth, Mary and
Medina, Mónica},
title = {Coral life history and symbiosis: Functional genomic resources for
two reef building Caribbean corals, Acropora palmata and Montastraea
faveolata},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {97},
number = {1},
abstract = {BACKGROUND:Scleractinian corals are the foundation of reef ecosystems
in tropical marine environments. Their great success is due to interactions
with endosymbiotic dinoflagellates (Symbiodinium spp.), with which
they are obligately symbiotic. To develop a foundation for studying
coral biology and coral symbiosis, we have constructed a set of cDNA
libraries and generated and annotated ESTs from two species of corals,
Acropora palmata and Montastraea faveolata.RESULTS:We generated 14,588
(Ap) and 3,854 (Mf) high quality ESTs from five life history/symbiosis
stages (spawned eggs, early-stage planula larvae, late-stage planula
larvae either infected with symbionts or uninfected, and adult coral).
The ESTs assembled into a set of primarily stage-specific clusters,
producing 4,980 (Ap), and 1,732 (Mf) unigenes. The egg stage library,
relative to the other developmental stages, was enriched in genes
functioning in cell division and proliferation, transcription, signal
transduction, and regulation of protein function. Fifteen unigenes
were identified as candidate symbiosis-related genes as they were
expressed in all libraries constructed from the symbiotic stages
and were absent from all of the non symbiotic stages. These include
several DNA interacting proteins, and one highly expressed unigene
(containing 17 cDNAs) with no significant protein-coding region.
A significant number of unigenes (25) encode potential pattern recognition
receptors (lectins, scavenger receptors, and others), as well as
genes that may function in signaling pathways involved in innate
immune responses (toll-like signaling, NFkB p105, and MAP kinases).
Comparison between the A. palmata and an A. millepora EST dataset
identified ferritin as a highly expressed gene in both datasets that
appears to be undergoing adaptive evolution. Five unigenes appear
to be restricted to the Scleractinia, as they had no homology to
any sequences in the nr databases nor to the non-scleractinian cnidarians
Nematostella vectensis and Hydra magnipapillata.CONCLUSION:Partial
sequencing of 5 cDNA libraries each for A. palmata and M. faveolata
has produced a rich set of candidate genes (4,980 genes from A. palmata,
and 1,732 genes from M. faveolata) that we can use as a starting
point for examining the life history and symbiosis of these two species,
as well as to further expand the dataset of cnidarian genes for comparative
genomics and evolutionary studies.},
doi = {10.1186/1471-2164-9-97},
issn = {1471-2164},
pubmedid = {18298846},
url = {http://www.biomedcentral.com/1471-2164/9/97}
}
@ARTICLE{Schweikl2008,
author = {Schweikl, Helmut and Hiller, Karl-Anton and Eckhardt, Alexander and
Bolay, Carola and Spagnuolo, Gianrico and Stempfl, Thomas and Schmalz,
Gottfried},
title = {Differential gene expression involved in oxidative stress response
caused by triethylene glycol dimethacrylate},
journal = {Biomaterials},
year = {2008},
volume = {29},
pages = {1377--1387},
number = {10},
month = apr,
abstract = {Triethylene glycol dimethacrylate (TEGDMA) is a comonomer that is
released from dental resin-based materials into hydrophilic solvents.
The compound reduces cell vitality, and causes genotoxicity in mammalian
cells in vitro. Here, we used gene expression profiling, combined
with pathway analysis tools, to identify the molecular events associated
with TEGDMA cytotoxicity in human fibroblasts using Affymetrix HG-U133A
2.0 GeneChip arrays. Increased ROS production and a cell cycle delay
caused by 3 mm TEGDMA after a 6 h exposure were related to a cell
response at the transcriptional level. The predominant biological
processes associated with the genes that were differentially expressed
in untreated and treated cell cultures included oxidative stress,
cellular growth, proliferation and morphology, cell death, gene expression
as well as DNA replication and repair. The most significantly upregulated
genes were GEM (17-fold), KLHL24, DDIT4, TGIF, DUSP5 and ATF3, which
are all related to the regulation of the cell structure, stress response,
and cell proliferation. TXNIP was the most downregulated transcript
(five-fold), whose gene product regulates the cellular redox balance.
The downregulation of NRG1, ASPM, FBXO5, and PLK2 is linked to the
regulation of cell proliferation and cell structure. The underlying
mechanisms of the up- and downregulation of genes seem to be activated
by the production of ROS, and the related regulation of the cellular
redox balance disturbed in the presence of TEGDMA appears to be of
the utmost importance. The coordinated induction of genes coding
for oxidative stress response and antioxidant proteins is a critical
mechanism of protection against TEGDMA-induced cell damage.},
issn = {0142-9612},
keywords = {Dental resin, Dimethacrylate, TEGDMA, Oxidative stress, Gene expression,
Affymetrix},
url = {http://www.sciencedirect.com/science/article/B6TWB-4RFKKKM-2/2/a41736ef581fb471132f0171ff3b2e23}
}
@ARTICLE{Schweitzer2006,
author = {Schweitzer, Natalie B. and Alessio, Helaine M. and Berry, Stephen
D. and Roeske, Kirk and Hagerman, Ann E.},
title = {Exercise-induced changes in cardiac gene expression and its relation
to spatial maze performance},
journal = {Neurochemistry International},
year = {2006},
volume = {48},
pages = {9--16},
number = {1},
month = jan,
abstract = {Cognitive performance is sensitive to both neural and non-neural changes
induced by physical activity and inactivity. This study investigated
whether access to physical activity outside a standard laboratory
animal cage affected cognitive performance as measured by navigation
of a spatial maze. It also examined gene expression in heart tissue
for genes associated with cardiovascular function given recent reports
of cognitive impairment associated with hyperlipidemia. Furthermore,
we measured expression of neural-regulatory genes typically expressed
in brain, but also found in cardiac tissue. Male Sprague-Dawley rats
(n = 72) were separated into three groups having different access
to physical activity: none outside a standard cage, twice-weekly
physical activity, and every other day exercise on a running wheel.
Compared with a sedentary group, spatial maze performance was enhanced
in animals that had access to physical activity, either twice-weekly
in a large box or every other day on a running wheel. Both the cardiovascular
and neural-related genes expressed in the heart were distinguished
by access to physical activity. Several genes that are associated
with heart rate, cholesterol biosynthesis, blood pressure, and cell
adhesion regulation, including GJA1, FDFT1, EDN1, and CD36, differed
in animals based on access to physical activity. Neural-related genes
expressed in cardiac tissue associated with neurite outgrowth, neuroplasticity,
and neurogenesis including RTN4, HOMER2, ACTB, NCDN, KIF5B, and HMGB2,
were expressed differently among the three groups. Significant shifts
in ten cardiovascular and neural-related gene expressions in cardiac
tissue were associated with physical activity and may have influenced
learning and performance on a spatial maze.},
issn = {0197-0186},
keywords = {Microarray, Spatial maze, Cardiac, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6T0B-4H7T0BH-1/2/2c40fd2ce45f4b2bd5a2a45b65af988a}
}
@ARTICLE{Schweitzer2005,
author = {Schweitzer, Natalie B. and Alessio, Helaine M. and Hagerman, Ann
E. and Roy, Sashwati and Sen, Chandan K. and Nagy, Szilvia and Byrnes,
Robyn N. and Philip, Ben N. and Woodward, Jane L. and Wiley, Ronald
L.},
title = {Access to exercise and its relation to cardiovascular health and
gene expression in laboratory animals},
journal = {Life Sciences},
year = {2005},
volume = {77},
pages = {2246--2261},
number = {18},
month = sep,
abstract = {The interaction between genes and environment can influence cardiovascular
disease (CVD). This 16 month study investigated if genes associated
with cardiovascular (CV) regulation were expressed differently in
animals having: 1) no access to physical activity or exercise (SED),
2) access to hour-long, twice weekly activity (PA), and 3) access
every-other-day to a running wheel (EX). Out of 31,000 genes, a CV
subset comprising 44 genes was investigated. Ten genes from this
subset were expressed differently in EX compared with SED, and 34
genes were expressed differently in PA compared with SED (p < 0.05).
Total cholesterol (70 ± 8 vs. 101 ± 9 mg dl- 1), triglycerides (104 ± 8
vs. 127 ± 4 mg dl- 1), resting systolic blood pressure (130 ± 3 vs.
141 ± 3 mmHg), mean arterial pressure (110 ± 2 vs. 120 ± 2 mmHg)
and heart rate (380 ± 6 vs. 405 ± 9 beats min- 1) were lower in EX
compared with SED (p < 0.05), but intracellular adhesion molecule
levels did not differ among groups. Mean gene expressions for Gja1,
Fdft1, Edn1, Cd36, and Hmgb2 differed in animals according to access
to physical activity. These genes play roles in heart rate, cholesterol
biosynthesis, blood pressure, cell adhesion, and transcription and
neurogenesis regulation, respectively. In conclusion, a total of
44 CV genes were expressed differently in SED compared to PA and
EX; and SED showed more physiological evidence of CVD.},
issn = {0024-3205},
keywords = {Oxidative stress, Physical activity, Hypokinesis, Cardiovascular,
DNA microarray, Edn1, Hmgb2, Cd36, Gja1, Fdft1},
url = {http://www.sciencedirect.com/science/article/B6T99-4GJM41X-1/2/0741ac048edbd08ec63f8044afc8bf5e}
}
@ARTICLE{Schweizer2008,
author = {Schweizer, Liang and Rizzo, Cheryl and Spires, Thomas and Platero,
J Suso and Wu, Qiuyan and Lin, Tai-An and Gottardis, Marco and Attar,
Ricardo},
title = {The androgen receptor can signal through Wnt/ß-Catenin in prostate
cancer cells as an adaptation mechanism to castration levels of androgens},
journal = {BMC Cell Biology},
year = {2008},
volume = {9},
pages = {4},
number = {1},
abstract = {BACKGROUND:A crucial event in Prostate Cancer progression is the conversion
from a hormone-sensitive to a hormone-refractory disease state. Correlating
with this transition, androgen receptor (AR) amplification and mutations
are often observed in patients failing hormonal ablation therapies.
ß-Catenin, an essential component of the canonical Wnt signaling
pathway, was shown to be a coactivator of the AR signaling in the
presence of androgens. However, it is not yet clear what effect the
increased levels of the AR could have on the Wnt signaling pathway
in these hormone-refractory prostate cells.RESULTS:Transient transfections
of several human prostate cancer cell lines with the AR and multiple
components of the Wnt signaling pathway demonstrate that the AR overexpression
can potentiate the transcriptional activities of Wnt/ß-Catenin signaling.
In addition, the simultaneous activation of the Wnt signaling pathway
and overexpression of the AR promote prostate cancer cell growth
and transformation at castration levels of androgens. Interestingly,
the presence of physiological levels of androgen or other AR agonists
inhibits these effects. These observations are consistent with the
nuclear co-localization of the AR and ß-Catenin shown by immunohistochemistry
in human prostate cancer samples. Furthermore, chromatin immunoprecipitation
assays showed that Wnt3A can recruit the AR to the promoter regions
of Myc and Cyclin D1, which are well-characterized downstream targets
of the Wnt signalling pathway. The same assays demonstrated that
the AR and ß-Catenin can be recruited to the promoter and enhancer
regions of a known AR target gene PSA upon Wnt signaling. These results
suggest that the AR is promoting Wnt signaling at the chromatin level.CONCLUSION:Our
findings suggest that the AR signaling through the Wnt/ß-Catenin
pathway should be added to the well established functional interactions
between both pathways. Moreover, our data show that via this interaction
the AR could promote prostate cell malignancy in a ligand-independent
manner.},
doi = {10.1186/1471-2121-9-4},
issn = {1471-2121},
owner = {Meike Kuschel},
pubmedid = {18218096},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2121/9/4}
}
@ARTICLE{Schwenzer2007,
author = {Schwenzer, Nina F. and Bantleon, Rüdiger and Maurer, Brigitte and
Kehlbach, Rainer and Schraml, Christina and Claussen, Claus D. and
Rodegerdts, Enno},
title = {Do static or time-varying magnetic fields in magnetic resonance imaging
(3.0 T) alter protein–gene expression?—A study on human embryonic
lung fibroblasts},
journal = {J. Magn. Reson. Imaging},
year = {2007},
volume = {26},
pages = {1210--1215},
number = {5},
abstract = {Abstract 10.1002/jmri.21145.abs Purpose To evaluate the influence
of magnetic resonance imaging (MRI) on gene expression in embryonic
human lung fibroblasts (Hel 299). Materials and Methods The cells
were exposed to the static magnetic field and to a turbo spin-echo
sequence of an MR scanner at 3.0 Tesla. An MR group (exposed) and
a control group (sham-exposed) were set up using a special MR-compatible
incubation system. The exposure time was two hours. Gene expression
profiles were studied using a complementary deoxyribonucleic acid
(cDNA) microarray containing 498 known genes involved in transcription,
intracellular transport, structure/junction/adhesion or extracellular
matrix, signaling, host defense, energetics, metabolism, cell shape,
and death. Results No changes in gene expression were found in either
group (exposed or sham-exposed cells) at the end of a two-hour exposure
for any of the 498 tested protein genes. Conclusion The results suggest
that MRI has no influence on protein–gene expression in eugenic
human lung cells. J. Magn. Reson. Imaging 2007;26:1210–1215. ©
2007 Wiley-Liss, Inc.},
issn = {1522-2586},
keywords = {magnetic resonance imaging, safety, cDNA microarray, protein–gene
expression, 3 T},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jmri.21145}
}
@ARTICLE{Schweyer2007,
author = {Schweyer, S and Bachem, A and Bremmer, F and Steinfelder, HJ and
Soruri, A and Wagner, W and Pottek, T and Thelen, P and Hopker, WW
and Radzun, HJ and Fayyazi, A},
title = {Expression and function of protein phosphatase PP2A in malignant
testicular germ cell tumours},
journal = {J. Pathol.},
year = {2007},
volume = {213},
pages = {72--81},
number = {1},
abstract = {Abstract 10.1002/path.2203.abs Testicular germ cell tumours (TGCT)
represent the most common malignancy in young males. We reported
previously that two prototype members of the mitogen-activated protein
kinase (MAPK) family, the MAPK ERK kinase (MEK) and extracellular
signal-regulated kinase (ERK), are inactive in malignant testicular
germ cells and become active after drug stimulation, leading to apoptosis
of tumour cells. In this study, we asked whether the protein phosphatase
PP2A, a known inhibitor of the MEK–ERK pathway, participates in
the proliferation and/or apoptosis of primary TGCT (n = 48) as well
as two TGCT cell lines (NTERA and NCCIT). Quantitative RT–PCR,
immunohistochemistry, western blot analyses and phosphatase assay
indicate that primary TGCT as well as TGCT cell lines express PP2A
and that PP2A is active in TGCT cell lines. The inhibition of PP2A
by application of two PP2A inhibitors, cantharidic acid (CA) and
okadaic acid (OA), results in a significant increase in caspase-3-mediated
apoptosis of TGCT cell lines. Thereby, PP2A inhibition was accompanied
by phosphorylation and activation of MEK and ERK. Functional assays
using the MEK inhibitor PD98059 demonstrated that the phosphorylation
of MEK and ERK was required for the induction of caspase-3-mediated
apoptosis of malignant germ cells. Thus, our data suggest that inhibition
of PP2A mediates its apoptosis-inducing effect on TGCT through activation
of the MEK–ERK signalling pathway that leads to caspase-3-mediated
apoptosis of tumour cells. In addition our results support previous
observations that PP2A exerts an anti-apoptotic effect on malignant
tumour cells. Copyright © 2007 Pathological Society of Great Britain
and Ireland. Published by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {testis, TGCT, immunohistochemistry, real-time PCR, apoptosis, PP2A,
MEK–ERK},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2203}
}
@ARTICLE{Schwinkendorf2009,
author = {Schwinkendorf, D. and Gallant, P.},
title = {The conserved Myc box 2 and Myc box 3 regions are important, but
not essential, for Myc function in vivo},
journal = {Gene},
year = {2009},
volume = {436},
pages = {90--100},
number = {1-2},
month = may,
abstract = {Myc proto-oncoproteins are important regulators of growth and proliferation
in development. Their functions have been evolutionarily conserved
from insects to vertebrates, although the sequence conservation is
limited to a few short domains. Here, we analyze the requirement
for the most highly conserved domains, called Myc boxes 2 and 3 (MB2
and MB3), and for the weakly conserved N-terminus for the biological
activity of the single Drosophila Myc protein in the animal in vivo.
We find that a Myc mutant lacking the N-terminus retains very little
activity, whereas Myc transgenes carrying a deletion of MB3 have
a moderately increased ability to promote growth and apoptosis; mutation
of MB2 reduces transcriptional output and the biological activities
of Myc. Surprisingly though, Myc without MB2 retains enough activity
to partially rescue the lethality of a Myc null mutation. Thus, although
MB2 and MB3 are highly conserved in evolution, loss of either domain
has comparatively mild consequences on Myc activity in vivo.},
issn = {0378-1119},
keywords = {Growth, Apoptosis, Transcription},
url = {http://www.sciencedirect.com/science/article/B6T39-4VP667R-1/2/72a4952f47ef22938bdccdc0b923e810}
}
@ARTICLE{Schwoerer2008,
author = {Schwoerer, Alexander Peter and Melnychenko, Ivan and Goltz, Diane
and Hedinger, Nils and Broichhausen, Irene and El-Armouche, Ali and
Eschenhagen, Thomas and Volk, Tilmann and Ehmke, Heimo},
title = {Unloaded rat hearts in vivo express a hypertrophic phenotype of cardiac
repolarization},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2008},
volume = {45},
pages = {633--641},
number = {5},
month = nov,
abstract = {Cardiac unloading with left ventricular assist devices is increasingly
used to treat patients with severe heart failure. Unloading has been
shown to improve systolic and diastolic function, but its impact
on the repolarization of left ventricular myocytes is not known.
Unloaded hearts exhibit similar patterns of gene expression as hearts
subjected to an increased hemodynamic load. We therefore hypothesized
that cardiac unloading also replicates the alterations in action
potential and underlying repolarizing ionic currents found in pressure-overload
induced cardiac hypertrophy. Left ventricular unloading was induced
by heterotopic heart transplantation in syngenic male Lewis rats.
Action potentials and underlying K+ and Ca2+ currents were investigated
using whole-cell patch-clamp technique. Real-time RT-PCR was used
to quantify mRNA expression of Kv4.2, Kv4.3, and KChIP2. Unloading
markedly prolonged cardiac action potentials and suppressed the amplitude
of several repolarizing K+ currents, in particular of the transient
outward K+ current Ito, in both, epicardial and endocardial myocytes.
The reduction of Ito was associated with significantly lower levels
of Kv4.2 and Kv4.3 mRNAs in epicardial myocytes, and of KChIP2 mRNA
in endocardial myocytes. Concomitantly, the L-type Ca2+ current was
increased in myocytes of unloaded hearts. Collectively, these results
show that left ventricular unloading induces a profound remodelling
of cardiac repolarization with action potential prolongation, downregulation
of repolarizing K+ currents and upregulation of the L-type Ca2+ current.
This indicates that unloaded rat hearts in vivo express a hypertrophic
phenotype of cardiac repolarization at the cellular and the molecular
level.},
issn = {0022-2828},
keywords = {Left ventricular unloading, Heterotopic heart transplantation, Atrophic
remodelling, Repolarization, Cellular electrophysiology, K+ channels,
Ca2+ channels},
url = {http://www.sciencedirect.com/science/article/B6WK6-4S1C8JY-1/2/29b3675006e2043d5835f178cb88917c}
}
@ARTICLE{SchA¤fer2009,
author = {Schäfer, Patrick and Pfiffi, Stefanie and Voll, Lars M. and Zajic,
Doreen and Chandler, Peter M. and Waller, Frank and Scholz, Uwe and
Pons-Kühnemann, Jörn and Sonnewald, Sophia and Sonnewald, Uwe and
Kogel, Karl-Heinz},
title = {Manipulation of plant innate immunity and gibberellin as factor of
compatibility in the mutualistic association of barley roots with
Piriformospora indica},
journal = {The Plant Journal},
year = {2009},
volume = {59},
pages = {461--474},
number = {3},
abstract = {Summary Fungi of the order Sebacinales (Basidiomycota) are involved
in a wide spectrum of mutualistic symbioses with various plants,
thereby exhibiting unique potential for biocontrol strategies. Piriformospora
indica, a model organism of this fungal order, is able to increase
the biomass and grain yield of crop plants, and induces local and
systemic resistance to fungal diseases and tolerance to abiotic stress.
To elucidate the molecular basis for root colonization, we characterized
the interaction of P. indica with barley roots by combining global
gene expression profiling, metabolic profiling, and genetic studies.
At the metabolic level, we show that fungal colonization reduces
the availability of free sugars and amino acids to the root tip.
At the transcriptional level, consecutive interaction stages covering
pre-penetration-associated events and progressing through to root
colonization showed differential regulation of signal perception
and transduction components, secondary metabolism, and genes associated
with membrane transport. Moreover, we observed stage-specific up-regulation
of genes involved in phytohormone metabolism, mainly encompassing
gibberellin, auxin and abscisic acid, but salicylic acid-associated
gene expression was suppressed. The changes in hormone homoeostasis
were accompanied with a general suppression of the plant innate immune
system. Further genetic studies showed reduced fungal colonization
in mutants that are impaired in gibberellin synthesis as well as
perception, and implicate gibberellin as a modulator of the root’s
basal defence. Our data further reveal the complexity of compatibility
mechanisms in host–microbe interactions, and identify gibberellin
signaling as potential target for successful fungi.},
issn = {1365-313X},
keywords = {compatibility, gibberellin, plant defence, plant hormone, symbiosis,
mutualism},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2009.03887.x}
}
@ARTICLE{SchA¤fer-Somi2009,
author = {Schäfer-Somi, S and Klein, D and Beceriklisoy, HB and Sabitzer,
S and Ay, SS and Agaoglu, AR and Kücükaslan, I and Kaya, D and
Aksoy, OA and Aslan, S},
title = {Uterine Progesterone Receptor and Leukaemia Inhibitory Factor mRNA
Expression in Canine Pregnancy},
journal = {Reproduction in Domestic Animals},
year = {2009},
volume = {44},
pages = {109--114},
abstract = {Contents The study investigated the expression of genes for progesterone
receptor (PR) and for the cytokine leukaemia inhibitory factor (LIF)
in the uterine tube and uterine horn tissues from pregnant and non-pregnant
bitches. The aim was to study whether a relation existed between
the likely biological effectiveness of progesterone (P4) and the
change in the uterine expression of LIF mRNA during pregnancy, as
has been described in primates. For this purpose, 20 pregnant bitches
were ovariohysterectomized after being allotted to three groups according
to gestational age (pre-implantation: days 10 to 12, n = 7; peri-implantation:
days 18 to 25, n = 7; post-placentation: days 28 to 45, n = 7).
Tissue samples were obtained from the uterine tubes, one uterine
horn (including placentation sites and interplacental sites in bitches
that had already implanted) and the corpus uteri, stored at −80°C,
and then analysed by qualitative and quantitative PCR for PR and
LIF mRNA expression. From the pre-implantation to the placentation
stage, a decrease in the relative expression of PR mRNA in uterine
tissue was obvious and significant when expressed relative to β-actin
(11.2 ± 6.8 vs 2.7 ± 1.9; p < 0.05). However, over the same
period, the relative expression of LIF mRNA increased (10.1 ± 16.1
vs 50.0 ± 32.3; p < 0.05). In addition, PR mRNA went from being
detectable to no longer detectable in the uterine tube, and no longer
detectable in interplacental-site uterine tissue. We conclude that
LIF is important for the establishment of canine pregnancy; that
decreased uterine PR mRNA expression may contribute to the increase
in uterine LIF mRNA; and, that the ability of the embryo to preserve
PR mRNA expression at implantation and placentation sites while expression
is lost in the remainder of the uterus represent an effect important
to the establishment and maintenance of pregnancy. We additionally
propose that canine embryo secretory proteins have a regulatory effect
on both PR and LIF before as well as at and after implantation.},
issn = {1439-0531},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0531.2009.01390.x}
}
@ARTICLE{SchA¶nfelder2011,
author = {Schönfelder, Martin and Hofmann, Hande and Anielski, Patricia and
Thieme, Detlef and Oberhoffer, Renate and Michna, Horst},
title = {Gene expression profiling in human whole blood samples after controlled
testosterone application and exercise},
journal = {Drug Testing and Analysis},
year = {2011},
volume = {3},
pages = {652--660},
number = {10},
abstract = {Doping with anabolic agents is regulated within a number of sports.
Testosterone and its functional analogs are popular compounds for
increasing muscle mass, physical performance, recovery, and reducing
body fat. While routine tests for anabolic drugs exist (e.g. hair,
urine, and blood analysis), the aim of the present study is to determine
specific gene expression profiles (induced by testosterone and exercise)
which may be used as effective biomarkers to determine the use of
anabolic drugs. In this study, whole blood samples of 19 male volunteers
were analyzed by semi-quantitative real-time polymerase chain reaction
(RT-PCR) for gene expression profiles in the context of exercise
and transdermal testosterone application (1.5 mg/kg body weight).
The hormone application was monitored by urine and saliva analysis
for testosterone. Both urinary and saliva levels indicate that transdermal
testosterone application leads to an increase of testosterone, especially
after exercise. RT-PCR results showed a clear variation in the expression
of target genes as well as established housekeeping genes. Only one
of the nine common housekeeping genes, cyclophilin b (PPIB), appears
to be independent of both exercise and testosterone. Out of 14 candidate
genes, five are unregulated; all others were more or less influenced
by the mentioned variables. Only interleukin-6 appeared to be exclusively
dependent on long-term testosterone application. This study indicates
that many genes are not influenced by testosterone alone while exercise
modulates gene expression in whole blood samples. As such, exercise
must be considered when validating gene expression techniques for
doping analysis. Copyright © 2011 John Wiley & Sons, Ltd.},
doi = {10.1002/dta.360},
issn = {1942-7611},
keywords = {gene expression, testosterone, exercise, doping analysis, whole blood
cell, salivary testosterone, urinary testosterone},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/dta.360}
}
@ARTICLE{Schaefer2010a,
author = {Schäfer, Richard and Bantleon, Rüdiger and Kehlbach, Rainer and Siegel,
Georg and Wiskirchen, Jakub and Wolburg, Hartwig and Kluba, Torsten
and Eibofner, Frank and Northoff, Hinnak and Claussen, Claus and
Schlemmer, Heinz-Peter},
title = {Functional investigations on human mesenchymal stem cells exposed
to magnetic fields and labeled with clinically approved iron nanoparticles},
journal = {BMC Cell Biology},
year = {2010},
volume = {11},
pages = {22},
number = {1},
abstract = {BACKGROUND:For clinical applications of mesenchymal stem cells (MSCs),
labeling and tracking is crucial to evaluate cell distribution and
homing. Magnetic resonance imaging (MRI) has been successfully established
detecting MSCs labeled with superparamagnetic particles of iron oxide
(SPIO). Despite initial reports that labeling of MSCs with SPIO is
safe without affecting the MSC's biology, recent studies report on
influences of SPIO-labeling on metabolism and function of MSCs. Exposition
of cells and tissues to high magnetic fields is the functional principle
of MRI. In this study we established innovative labeling protocols
for human MSCs using clinically established SPIO in combination with
magnetic fields and investigated on functional effects (migration
assays, quantification of colony forming units, analyses of gene
and protein expression and analyses on the proliferation capacity,
the viability and the differentiation potential) of magnetic fields
on unlabeled and labeled human MSCs. To evaluate the imaging properties,
quantification of the total iron load per cell (TIL), electron microscopy,
and MRI at 3.0 T were performed.RESULTS:Human MSCs labeled with SPIO
permanently exposed to magnetic fields arranged and grew according
to the magnetic flux lines. Exposure of MSCs to magnetic fields after
labeling with SPIO significantly enhanced the TIL compared to SPIO
labeled MSCs without exposure to magnetic fields resulting in optimized
imaging properties (detection limit: 1,000 MSCs). Concerning the
TIL and the imaging properties, immediate exposition to magnetic
fields after labeling was superior to exposition after 24 h. On functional
level, exposition to magnetic fields inhibited the ability of colony
formation of labeled MSCs and led to an enhanced expression of lipoprotein
lipase and peroxisome proliferator-activated receptor-? in labeled
MSCs under adipogenic differentiation, and to a reduced expression
of alkaline phosphatase in unlabeled MSCs under osteogenic differentiation
as detected by qRT-PCR. Moreover, microarray analyses revealed that
exposition of labeled MSCs to magnetic fields led to an up regulation
of CD93 mRNA and cadherin 7 mRNA and to a down regulation of Zinc
finger FYVE domain mRNA. Exposition of unlabeled MSCs to magnetic
fields led to an up regulation of CD93 mRNA, lipocalin 6 mRNA, sialic
acid acetylesterase mRNA, and olfactory receptor mRNA and to a down
regulation of ubiquilin 1 mRNA. No influence of the exposition to
magnetic fields could be observed on the migration capacity, the
viability, the proliferation rate and the chondrogenic differentiation
capacity of labeled or unlabeled MSCs.CONCLUSIONS:In our study an
innovative labeling protocol for tracking MSCs by MRI using SPIO
in combination with magnetic fields was established. Both, SPIO and
the static magnetic field were identified as independent factors
which affect the functional biology of human MSCs. Further in vivo
investigations are needed to elucidate the molecular mechanisms of
the interaction of magnetic fields with stem cell biology.},
doi = {10.1186/1471-2121-11-22},
issn = {1471-2121},
pubmedid = {20370915},
url = {http://www.biomedcentral.com/1471-2121/11/22}
}
@ARTICLE{Schuetze2011,
author = {Schütze, Tatjana and Rubelt, Florian and Repkow, Julia and Greiner,
Nicole and Erdmann, Volker A. and Lehrach, Hans and Konthur, Zoltán
and Glökler, Jörn},
title = {A streamlined protocol for emulsion polymerase chain reaction and
subsequent purification},
journal = {Analytical Biochemistry},
year = {2011},
volume = {410},
pages = {155--157},
number = {1},
month = mar,
abstract = {Compartmentalization of polymerase chain reaction (PCR) reduces artifacts,
especially when complex libraries are amplified. It allows clonal
amplification of templates from complex mixtures in a bias-free manner.
Here we describe a rapid, straightforward, and easy protocol for
PCR in a water-in-oil emulsion (ePCR) including sample recovery by
DNA purification. Furthermore, no special laboratory equipment is
needed and inexpensive components are used. Therefore, our flexible
protocol allows ePCR to be readily implemented in daily routine experiments
for a broad range of applications.},
issn = {0003-2697},
url = {http://www.sciencedirect.com/science/article/pii/S0003269710007426}
}
@ARTICLE{Scicchitano2006,
author = {Scicchitano, Marshall S. and Dalmas, Deidre A. and Bertiaux, Melissa
A. and Anderson, Shawn M. and Turner, Leah R. and Thomas, Roberta
A. and Mirable, Rossana and Boyce, Rogely W.},
title = {Preliminary Comparison of Quantity, Quality, and Microarray Performance
of RNA Extracted From Formalin-fixed, Paraffin-embedded, and Unfixed
Frozen Tissue Samples},
journal = {J. Histochem. Cytochem.},
year = {2006},
volume = {54},
pages = {1229--1237},
number = {11},
month = nov,
abstract = {Microarrays have been used to simultaneously monitor the expression
of thousands of genes from biological samples, an approach that can
potentially uncover previously unrecognized functions of genes. Microarray
analyses can rarely be conducted retrospectively because of the requirement
for RNA to be obtained from fresh or unfixed frozen tissues. Archived
pathology specimens would need to be used for retrospective analyses,
and these are typically preserved as formalin-fixed, paraffin-embedded
(FFPE) tissue. Formalin-fixed tissues have been shown to yield compromised
RNA compared with that obtained from frozen tissue. To begin to assess
the performance of RNA extracted from FFPE samples on a microarray
format, we compared RNA from a model system of pelleted lipopolysaccharide-stimulated
human bone marrow stromal cells that were snap frozen with RNA from
FFPE cells. RNA integrity and Affymetrix quality control parameters
were assessed, and differentially regulated genes were analyzed with
Ingenuity Pathway Analysis software. Results demonstrate that both
snap-frozen and FFPE samples yielded intact RNA suitable for amplification
prior to Affymetrix GeneChip analysis. Although some transcriptional
information was lost with RNA extracted from the FFPE samples, Ingenuity
Pathway Analysis revealed that the major pathways identified as affected
by drug treatment were similar. Results show that FFPE samples are
amenable to Affymetrix GeneChip analysis, expanding the possibility
for expression profiling on archived tissue blocks in pathology laboratories.
(J Histochem Cytochem 54:1229-1237, 2006)},
url = {http://www.jhc.org/cgi/content/abstract/54/11/1229}
}
@ARTICLE{Scime2010,
author = {Scimè, Anthony and Desrosiers, Justine and Trensz, Frédéric and Palidwor,
Gareth A. and Caron, Annabelle Z. and Andrade-Navarro, Miguel A.
and Grenier, Guillaume},
title = {Transcriptional profiling of skeletal muscle reveals factors that
are necessary to maintain satellite cell integrity during ageing},
journal = {Mechanisms of Ageing and Development},
year = {2010},
volume = {131},
pages = {9--20},
number = {1},
month = jan,
abstract = {Skeletal muscle ageing is characterized by faulty degenerative/regenerative
processes that promote the decline of its mass, strength, and endurance.
In this study, we used a transcriptional profiling method to better
understand the molecular pathways and factors that contribute to
these processes. To more appropriately contrast the differences in
regenerative capacity of old muscle, we compared it with young muscle,
where robust growth and efficient myogenic differentiation is ongoing.
Notably, in old mice, we found a severe deficit in satellite cells
activation. We performed expression analyses on RNA from the gastrocnemius
muscle of young (3-week-old) and old (24-month-old) mice. The differential
expression highlighted genes that are involved in the efficient functioning
of satellite cells. Indeed, the greatest number of up-regulated genes
in young mice encoded components of the extracellular matrix required
for the maintenance of the satellite cell niche. Moreover, other
genes included Wnt inhibitors (Wif1 and Sfrp2) and Notch activator
(Dner), which are putatively involved in the interconnected signalling
networks that control satellite cell function. The widespread expression
differences for inhibitors of TGFbeta signalling further emphasize
the shortcomings in satellite cell performance. Therefore, we draw
attention to the breakdown of features required to maintain satellite
cell integrity during the ageing process.},
issn = {0047-6374},
keywords = {Stem cell niche, Satellite cell, Ageing, Extracellular matrix, Gene
expression, Wnt, TGFbeta, Notch, Stromal cells},
url = {http://www.sciencedirect.com/science/article/B6T31-4XNW433-1/2/41b14885bc1956d22a60757a69048816}
}
@ARTICLE{Sciuto2005,
author = {Sciuto, Alfred M. and Phillips, Christopher S. and Orzolek, Linda
D. and Hege, Alison I. and Moran, Theodore S. and Dillman, James
F.},
title = {Genomic Analysis of Murine Pulmonary Tissue Following Carbonyl Chloride
Inhalation},
journal = {Chemical Research in Toxicology},
year = {2005},
volume = {18},
pages = {1654-1660},
number = {11},
doi = {10.1021/tx050126f},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx050126f},
url = {http://pubs.acs.org/doi/abs/10.1021/tx050126f}
}
@ARTICLE{Scotlandi2009,
author = {Scotlandi, Katia and Remondini, Daniel and Castellani, Gastone and
Manara, Maria Cristina and Nardi, Filippo and Cantiani, Lara and
Francesconi, Mirko and Mercuri, Mario and Caccuri, Anna Maria and
Serra, Massimo and Knuutila, Sakari and Picci, Piero},
title = {Overcoming Resistance to Conventional Drugs in Ewing Sarcoma and
Identification of Molecular Predictors of Outcome},
journal = {J. Clin. Oncol.},
year = {2009},
volume = {27},
pages = {2209--2216},
number = {13},
month = may,
abstract = {PurposeThe improvement of Ewing sarcoma (EWS) therapy is currently
linked to the discovery of strategies to select patients with poor
and good prognosis and of modified treatment regimens. In this study,
we analyzed the molecular factors governing EWS response to chemotherapy
to identify genetic signatures to be used for risk-adapted therapy.
Patients and MethodsMicroarray technology was used for profiling
30 primary tumors and seven metastases of patients who were classified
according to event-free survival. For selected genes, real-time polymerase
chain reaction was applied in 42 EWS primary tumors as validation
assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
test was used to evaluate in vitro drug sensitivity. ResultsWe identified
molecular signatures that reflect tumor resistance to chemotherapy.
Annotation analysis was applied to reveal the biologic functions
that critically influenced clinical outcome. The prognostic relevance
of glutathione metabolism pathway was validated. The expression of
MGST1, the microsomal glutathione S-transferase (GST), was found
to clearly predict EWS prognosis. MGST1 expression was associated
with doxorubicin chemosensitivity. This prompted us to assess the
in vitro effectiveness of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol
(NBDHEX), a new anticancer agent that efficiently inhibits GST enzymes.
Six cell lines were found to be sensitive to this new drug. ConclusionClassification
of EWS patients into high- and low-risk groups is feasible with restricted
molecular signatures that may have practical value at diagnosis for
selecting patients with EWS who are unresponsive to current treatments.
Glutathione metabolism pathway emerged as one of the most significantly
altered prognosis-associated pathway. NBDHEX is proposed as a new
potential therapeutic possibility.},
url = {http://jco.ascopubs.org/cgi/content/abstract/27/13/2209}
}
@ARTICLE{Scott2009,
author = {Scott, Cinda P. And Williams, Dean A. And Crawford, Douglas L.},
title = {The effect of genetic and environmental variation on metabolic gene
expression},
journal = {Molecular Ecology},
year = {2009},
volume = {18},
pages = {2832--2843},
number = {13},
abstract = {Abstract What is the relationship between genetic or environmental
variation and the variation in messenger RNA (mRNA) expression? To
address this, microarrays were used to examine the effect of genetic
and environmental variation on cardiac mRNA expression for metabolic
genes in three groups of Fundulus heteroclitus: (i) individuals sampled
in the field (field), (ii) field individuals acclimated for 6 months
to laboratory conditions (acclimated), or (iii) individuals bred
for 10 successive generations in a laboratory environment (G10).
The G10 individuals have significantly less genetic variation than
individuals obtained in the field and had a significantly lower variation
in mRNA expression across all genes in comparison to the other two
groups (PÂ =Â 0.001). When examining the gene specific variation,
22 genes had variation in expression that was significantly different
among groups with lower variation in G10 individuals than in acclimated
individuals. Additionally, there were fewer genes with significant
differences in expression among G10 individuals vs. either acclimated
or field individuals: 66 genes have statistically different levels
of expression vs. 107 or 97 for acclimated or field groups. Based
on the permutation of the data, these differences in the number of
genes with significant differences among individuals within a group
are unlikely to occur by chance (PÂ <Â 0.01). Surprisingly, variation
in mRNA expression in field individuals is lower than in acclimated
individuals. Relative to the variation among individual within a
group, few genes have significant differences in expression among
groups (seven, 2.3%) and none of these are different between acclimated
and field individuals. The results support the concept that genetic
variation affects variation in mRNA expression and also suggests
that temporal environmental variation associated with estuarine environments
does not increase the variation among individuals or add to the differences
among groups.},
issn = {1365-294X},
keywords = {Fundulus heteroclitus, gene expression evolutionary genomics, genetic
variation, microarray},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2009.04235.x}
}
@ARTICLE{Scott2011,
author = {D.J. Scott and A.S. Devonshire and Y.A. Adeleye and M.E. Schutte
and M.R. Rodrigues and T.M. Wilkes and M.G. Sacco and L. Gribaldo
and M. Fabbri and S. Coecke and M. Whelan and N. Skinner and A. Bennett
and A. White and C.A. Foy},
title = {Inter- and intra-laboratory study to determine the reproducibility
of toxicogenomics datasets},
journal = {Toxicology},
year = {2011},
volume = {290},
pages = {50 - 58},
number = {1},
abstract = {The application of toxicogenomics as a predictive tool for chemical
risk assessment has been under evaluation by the toxicology community
for more than a decade. However, it predominately remains a tool
for investigative research rather than for regulatory risk assessment.
In this study, we assessed whether the current generation of microarray
technology in combination with an in vitro experimental design was
capable of generating robust, reproducible data of sufficient quality
to show promise as a tool for regulatory risk assessment. To this
end, we designed a prospective collaborative study to determine the
level of inter- and intra-laboratory reproducibility between three
independent laboratories.
All test centres (TCs) adopted the same protocols for all aspects
of the toxicogenomic experiment including cell culture, chemical
exposure, RNA extraction, microarray data generation and analysis.
As a case study, the genotoxic carcinogen benzo[a]pyrene (B[a]P)
and the human hepatoma cell line HepG2 were used to generate three
comparable toxicogenomic data sets. High levels of technical reproducibility
were demonstrated using a widely employed gene expression microarray
platform. While differences at the global transcriptome level were
observed between the TCs, a common subset of B[a]P responsive genes
(n = 400 gene probes) was identified at all TCs which included
many genes previously reported in the literature as B[a]P responsive.
These data show promise that the current generation of microarray
technology, in combination with a standard in vitro experimental
design, can produce robust data that can be generated reproducibly
in independent laboratories. Future work will need to determine whether
such reproducible in vitro model(s) can be predictive for a range
of toxic chemicals with different mechanisms of action and thus be
considered as part of future testing regimes for regulatory risk
assessment.},
doi = {10.1016/j.tox.2011.08.015},
issn = {0300-483X},
keywords = {Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/pii/S0300483X11003192}
}
@ARTICLE{Scott2006,
author = {Scott, Karen P. and Martin, Jennifer C. and Campbell, Gillian and
Mayer, Claus-Dieter and Flint, Harry J.},
title = {Whole-Genome Transcription Profiling Reveals Genes Up-Regulated by
Growth on Fucose in the Human Gut Bacterium "Roseburia inulinivorans"},
journal = {J. Bacteriol.},
year = {2006},
volume = {188},
pages = {4340--4349},
number = {12},
month = jun,
abstract = {"Roseburia inulinivorans" is an anaerobic polysaccharide-utilizing
firmicute bacterium from the human colon that was identified as a
producer of butyric acid during growth on glucose, starch, or inulin.
R. inulinivorans A2-194 is also able to grow on the host-derived
sugar fucose, following a lag period, producing propionate and propanol
as additional fermentation products. A shotgun genomic microarray
was constructed and used to investigate the switch in gene expression
that is involved in changing from glucose to fucose utilization.
This revealed a set of genes coding for fucose utilization, propanediol
utilization, and the formation of propionate and propanol that are
up-regulated during growth on fucose. These include homologues of
genes that are implicated in polyhedral body formation in Salmonella
enterica. Dehydration of the intermediate 1,2-propanediol involves
an enzyme belonging to the new B12-independent glycerol dehydratase
family, in contrast to S. enterica, which relies on a B12-dependent
enzyme. A typical gram-positive agr-type quorum-sensing system was
also up-regulated in R. inulinivorans during growth on fucose. Despite
the lack of genome sequence information for this commensal bacterium,
microarray analysis has provided a powerful tool for obtaining new
information on its metabolic capabilities.},
url = {http://jb.asm.org/cgi/content/abstract/188/12/4340}
}
@ARTICLE{Scott2009a,
author = {Scott, Mary and Knight, Angus},
title = {Quantitative PCR Analysis for Fruit Juice Authentication Using PCR
and Laboratory-on-a-Chip Capillary Electrophoresis According to the
Hardy−Weinberg Law},
journal = {Journal of Agricultural and Food Chemistry},
year = {2009},
volume = {57},
pages = {4545-4551},
number = {11},
note = {PMID: 19438229},
doi = {10.1021/jf9002686},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf9002686},
url = {http://pubs.acs.org/doi/abs/10.1021/jf9002686}
}
@BOOK{Scott2008,
title = {Assaying Pain-Related Genes: Preclinical and Clinical Correlates},
publisher = {Academic Press},
year = {2008},
editor = {Basbaum, Allan I. and Kaneko, Akimichi and Shepherd, Gordon M. and
Westheimer, Gerald and Albright, Thomas D. and Masland, Richard H.
and Dallos, Peter and Oertel, Donata and Firestein, Stuart and Beauchamp,
Gary K. and Bushnell, M. Catherine and Kaas, Jon H. and Gardner,
Esther},
author = {Scott, V.E. and Davis-Taber, R. and Honore, P.},
pages = {165--173},
address = {New York},
abstract = {Identification of therapeutic targets for the treatment of chronic
pain is a major focus of the pharmaceutical industry. In particular
efforts have focused on the discovery of novel agents for the treatment
of neuropathic pain for which there is significant unmet medical
need. Following nerve injury, as neuropathic pain develops many physiological
changes occur in both the peripheral and central nervous system.
To assess the changes, microarray gene chip technology has provided
an excellent opportunity to examine RNA levels for multiple genes
simultaneously. In the pain arena, most studies have focused on the
evaluation of the expression profile of genes from entire tissues
(dorsal root ganglion or spinal cord) that contain heterogeneous
populations of neurons and glial cells, although a small number of
studies have examined subpopulations of neurons that have been isolated
by laser capture microdissection. While microarray is an excellent
tool to identify changes in expression of thousands of transcripts
simultaneously, additional detailed analysis of specific genes of
interest is critical to the usefulness of this approach for new target
identification. Confirmation of gene changes using quantitative reverse
transcriptase polymerase chain reaction is a first step followed
by when possible evaluation of protein levels using Western blot
analysis and immunohistochemistry. Although this approach provides
very useful information, it is not all encompassing as the function
of a protein can change due to post-translational modifications with
the overall level of the transcript being unaltered. However, microarray
gene chip technology offers an excellent opportunity to visualize
the many molecular transcripts that may play a role in the maintenance
of neuropathic pain. Furthermore, recent trends are utilizing microarray
gene chips to interrogate the genetic variability of patient populations
that may lead to both the identification of new disease targets and
tailoring of drug therapies to specific individuals.},
booktitle = {The Senses: A Comprehensive Reference},
issn = {978-0-12-370880-9},
keywords = {Dorsal root ganglion, laser capture microdissection, microarray, neuropathic
pain, quantitative RT-PCR, RNA, spinal nerve ligation},
url = {http://www.sciencedirect.com/science/article/B8SV0-4RD4KNB-4K/2/ae26c3bb1a0934cde266f5ed1c3cd6a0}
}
@ARTICLE{Scurr2008,
author = {Scurr, Lyndee L. and Guminski, Alexander D. and Chiew, Yoke-Eng and
Balleine, Rosemary L. and Sharma, Raghwa and Lei, Ying and Pryor,
Kylie and Wain, Gerard V. and Brand, Alison and Byth, Karen and Kennedy,
Catherine and Rizos, Helen and Harnett, Paul R. and deFazio, Anna},
title = {Ankyrin Repeat Domain 1, ANKRD1, a Novel Determinant of Cisplatin
Sensitivity Expressed in Ovarian Cancer},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6924--6932},
number = {21},
month = nov,
abstract = {Purpose: The standard of care for ovarian cancer includes platinum-based
chemotherapy. It is not possible, however, to predict clinical platinum
sensitivity or to design rational strategies to overcome resistance.
We used a novel approach to identify altered gene expression associated
with high sensitivity to cisplatin, to define novel targets to sensitize
tumor cells to platins and ultimately improve the effectiveness of
this widely used class of chemotherapeutics. Experimental Design:
Using differential display PCR, we identified genes differentially
expressed in a mutagenized cell line with unusual sensitivity to
cisplatin. The most highly differentially expressed gene was selected,
and its role in determining cisplatin sensitivity was validated by
gene transfection and small interfering RNA (siRNA) approaches, by
association of expression levels with cisplatin sensitivity in cell
lines, and by association of tumor expression levels with survival
in a retrospective cohort of 71 patients with serous ovarian adenocarcinoma.
Results: The most highly differently expressed gene identified was
ANKRD1, ankyrin repeat domain 1 (cardiac muscle). ANKRD1 mRNA levels
were correlated with platinum sensitivity in cell lines, and most
significantly, decreasing ANKRD1 using siRNA increased cisplatin
sensitivity >2-fold. ANKRD1 was expressed in the majority of ovarian
adenocarcinomas tested (62/71, 87%), and higher tumor levels of ANKRD1
were found in patients with worse outcome (overall survival, P =
0.013). Conclusions: These findings suggest that ANKRD1, a gene not
previously associated with ovarian cancer or with response to chemotherapy,
is associated with treatment outcome, and decreasing ANKRD1 expression,
or function, is a potential strategy to sensitize tumors to platinum-based
drugs.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/21/6924}
}
@ARTICLE{Scurr2010,
author = {Scurr, Lyndee L. and Pupo, Gulietta M. and Becker, Therese M. and
Lai, Ken and Schrama, David and Haferkamp, Sebastian and Irvine,
Mal and Scolyer, Richard A. and Mann, Graham J. and Becker, Jürgen
C. and Kefford, Richard F. and Rizos, Helen},
title = {IGFBP7 Is Not Required for B-RAF-Induced Melanocyte Senescence},
journal = {Cell},
year = {2010},
volume = {141},
pages = {717--727},
number = {4},
month = may,
abstract = {Summary Induction of senescence permanently restricts cellular proliferation
after oncogenic stimulation thereby acting as a potent barrier to
tumor development. The relevant effector proteins may therefore be
fundamental to cancer development. A recent study identified IGFBP7
as a secreted factor mediating melanocyte senescence induced by oncogenic
B-RAF, which is found commonly in cutaneous nevi. In contrast to
the previous report, we demonstrate that B-RAF signaling does not
induce IGFBP7 expression, nor the expression of the IGFBP7 targets,
BNIP3L, SMARCB1, or PEA15, in human melanocytes or fibroblasts. We
also found no correlation between B-RAF mutational status and IGFBP7
protein expression levels in 22 melanoma cell lines, 90 melanomas,
and 46 benign nevi. Furthermore, using a lentiviral silencing strategy
we show that B-RAF induces senescence in melanocytes and fibroblasts,
irrespective of the presence of IGFBP7. Therefore, we conclude that
the secreted protein IGFBP7 is dispensable for B-RAFV600E-induced
senescence in human melanocytes.},
issn = {0092-8674},
keywords = {HUMDISEASE, CELLBIO, SIGNALING},
url = {http://www.sciencedirect.com/science/article/B6WSN-502P17D-K/2/b902678e013793fb3c8b80fbcc1455ce}
}
@ARTICLE{Seagroves2010,
author = {Seagroves, Tiffany N. and Peacock, Danielle L. and Liao, Debbie and
Schwab, Luciana P. and Krueger, Robin and Handorf, Charles R. and
Haase, Volker H. and Johnson, Randall S.},
title = {VHL Deletion Impairs Mammary Alveologenesis but Is Not Sufficient
for Mammary Tumorigenesis},
journal = {Am. J. Pathol.},
year = {2010},
volume = {176},
pages = {2269--2282},
number = {5},
month = may,
abstract = {Overexpression of hypoxia inducible factor-1 (HIF-1){alpha}, which
is common in most solid tumors, correlates with poor prognosis and
high metastatic risk in breast cancer patients. Because HIF-1{alpha}
protein stability is tightly controlled by the tumor suppressor von
Hippel-Lindau (VHL), deletion of VHL results in constitutive HIF-1{alpha}
expression. To determine whether VHL plays a role in normal mammary
gland development, and if HIF-1{alpha} overexpression is sufficient
to initiate breast cancer, Vhl was conditionally deleted in the mammary
epithelium using the Cre/loxP system. During first pregnancy, loss
of Vhl resulted in decreased mammary epithelial cell proliferation
and impaired alveolar differentiation; despite these phenotypes,
lactation was sufficient to support pup growth. In contrast, in multiparous
dams, Vhl-/- mammary glands exhibited a progressive loss of alveolar
epithelium, culminating in lactation failure. Deletion of Vhl in
the epithelium also impacted the mammary stroma, as there was increased
microvessel density accompanied by hemorrhage and increased immune
cell infiltration. However, deletion of Vhl was not sufficient to
induce mammary tumorigenesis in dams bred continuously for up to
24 months of age. Moreover, co-deletion of Hif1a could not rescue
the Vhl-/--dependent phenotype as dams were unable to successfully
lactate during the first lactation. These results suggest that additional
VHL-regulated genes besides HIF1A function to maintain the proliferative
and regenerative potential of the breast epithelium.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/176/5/2269}
}
@ARTICLE{Searcy2012,
author = {Brian T. Searcy and Stephen M. Beckstrom-Sternberg and James S. Beckstrom-Sternberg
and Phillip Stafford and Angela L. Schwendiman and Jenifer Soto-Pena
and Michael C. Owen and Claire Ramirez and Joel Phillips and Nik
Veldhoen and Caren C. Helbing and Catherine R. Propper},
title = {Thyroid Hormone-Dependent Development in Xenopus laevis: A Sensitive
Screen of Thyroid Hormone Signaling Disruption by Municipal Wastewater
Treatment Plant Effluent},
journal = {General and Comparative Endocrinology},
year = {2012},
pages = { - },
number = {0},
abstract = {Because thyroid hormones (THs) are conserved modulators of development
and physiology, identification of compounds adversely affecting TH
signaling is critical to human and wildlife health. Anurans are an
established model for studying disruption of TH signaling because
metamorphosis is dependent upon the thyroid system. In order to strengthen
this model and identify new gene transcript biomarkers for TH disruption,
we performed DNA microarray analysis of Xenopus laevis tadpole tail
transcriptomes following treatment with triiodothyronine (T3). Comparison
of these results with previous studies in frogs and mammals identified
36 gene transcripts that were TH-sensitive across clades. We then
tested molecular biomarkers for sensitivity to disruption by exposure
to wastewater effluent (WWE). X. laevis tadpoles, exposed to WWE
from embryo through metamorphosis, exhibited an increased developmental
rate compared to controls. Cultured tadpole tails showed dramatic
increases in levels of four TH-sensitive gene transcripts (thyroid
hormone receptor β (TRβ), deiodinase type II (DIO2), and corticotropin
releasing hormone binding protein (CRHBP), fibroblast activation
protein α (FAPα)) when exposed to T3 and WWE extracts. TRβ, DIO2,
and CRHBP were identified as TH sensitive in other studies, while
FAPα mRNA transcripts were highly TH sensitive in our array. The
results validate the array and demonstrate TH-disrupting activity
by WWE. Our findings demonstrate the usefulness of cross-clade analysis
for identification of gene transcripts that provide sensitivity to
endocrine disruption. Further, the results suggest that development
is disrupted by exposure to complex mixes of compounds found in WWE
possibly through interference with TH signaling.},
doi = {10.1016/j.ygcen.2011.12.036},
issn = {0016-6480},
keywords = {Thyroid hormone},
url = {http://www.sciencedirect.com/science/article/pii/S0016648012000056?v=s5}
}
@ARTICLE{Sears2009,
author = {Sears, D. D. and Hsiao, G. and Hsiao, A. and Yu, J. G. and Courtney,
C. H. and Ofrecio, J. M. and Chapman, J. and Subramaniam, S.},
title = {Mechanisms of human insulin resistance and thiazolidinedione-mediated
insulin sensitization},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {18745--18750},
number = {44},
month = nov,
abstract = {Cellular and tissue defects associated with insulin resistance are
coincident with transcriptional abnormalities and are improved after
insulin sensitization with thiazolidinedione (TZD) PPAR{gamma} ligands.
We characterized 72 human subjects by relating their clinical phenotypes
with functional pathway alterations. We transcriptionally profiled
364 biopsies harvested before and after hyperinsulinemic-euglycemic
clamp studies, at baseline and after 3-month TZD treatment. We have
identified molecular and functional characteristics of insulin resistant
subjects and distinctions between TZD treatment responder and nonresponder
subjects. Insulin resistant subjects exhibited alterations in skeletal
muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose
tissue (e.g., mitochondrial metabolism and inflammation) that improved
relative to TZD-induced insulin sensitization. Pre-TZD treatment
expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from
insulin resistant subjects was linearly predictive of post-TZD insulin
sensitization. We have uniquely characterized coordinated cellular
and tissue functional pathways that are characteristic of insulin
resistance, TZD-induced insulin sensitization, and potential TZD
responsiveness.},
url = {http://www.pnas.org/cgi/content/abstract/106/44/18745}
}
@ARTICLE{Sebbane2006,
author = {Sebbane, Florent and Lemaitre, Nadine and Sturdevant, Daniel E. and
Rebeil, Roberto and Virtaneva, Kimmo and Porcella, Stephen F. and
Hinnebusch, B. Joseph},
title = {Adaptive response of Yersinia pestis to extracellular effectors of
innate immunity during bubonic plague},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {11766--11771},
number = {31},
month = aug,
abstract = {Yersinia pestis causes bubonic plague, characterized by an enlarged,
painful lymph node, termed a bubo, that develops after bacterial
dissemination from a fleabite site. In susceptible animals, the bacteria
rapidly escape containment in the lymph node, spread systemically
through the blood, and produce fatal sepsis. The fulminant progression
of disease has been largely ascribed to the ability of Y. pestis
to avoid phagocytosis and exposure to antimicrobial effectors of
innate immunity. In vivo microarray analysis of Y. pestis gene expression,
however, revealed an adaptive response to nitric oxide (NO)-derived
reactive nitrogen species and to iron limitation in the extracellular
environment of the bubo. Polymorphonuclear neutrophils recruited
to the infected lymph node expressed abundant inducible NO synthase,
and several Y. pestis homologs of genes involved in the protective
response to reactive nitrogen species were up-regulated in the bubo.
Mutation of one of these genes, which encodes the Hmp flavohemoglobin
that detoxifies NO, attenuated virulence. Thus, the ability of Y.
pestis to destroy immune cells and remain extracellular in the bubo
appears to limit exposure to some but not all innate immune effectors.
High NO levels induced during plague may also influence the developing
adaptive immune response and contribute to septic shock.},
url = {http://www.pnas.org/cgi/content/abstract/103/31/11766}
}
@ARTICLE{Secchi2011,
author = {Secchi, Francesca and Gilbert, Matthew E. and Zwieniecki, Maciej
A.},
title = {Transcriptome Response to Embolism Formation in Stems of Populus
trichocarpa Provides Insight into Signaling and the Biology of Refilling},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {1419-1429},
number = {3},
abstract = {The mechanism of embolism repair in transpiring plants is still not
understood, despite significant scientific effort. The refilling
process is crucial to maintaining stem transport capacity and ensuring
survival for plants experiencing dynamic changes in water stress.
Refilling air-filled xylem vessels requires an energy and water source
that can only be provided by adjacent living parenchyma cells. Here,
we report an analysis of the transcriptome response of xylem parenchyma
cells after embolism formation in Populus trichocarpa trees. Genes
encoding aquaporins, ion transporters, and carbohydrate metabolic
pathways were up-regulated, and there was a significant reduction
in the expression of genes responding to oxidative stress. Thus,
a novel view of the plant response to embolism emerges that suggests
a role for oxygen in embolized vessels as a signal triggering xylem
refilling and for the activity of cation transport as having a significant
role in the generation of the energy gradient necessary to heal embolized
vessels. These findings redefine current hypotheses surrounding the
refilling phenomenon and provide insight into the complexity of the
biological response to the seemingly simple physical event of xylem
embolism formation.},
doi = {10.1104/pp.111.185124},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/3/1419.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/3/1419}
}
@ARTICLE{Seear2008,
author = {Seear, PJ and Sweeney, GE},
title = {Stability of RNA isolated from post-mortem tissues of Atlantic salmon
(Salmo salar L.).},
journal = {Fish Physiology Biochemistry},
year = {2008},
volume = {34},
pages = {19-24--},
number = {1},
month = mar,
abstract = {Studies of post-mortem interval on the stability of RNA from a number
of various mammals have shown RNA to be stable for between 24 and
48 h following death. As yet there have been no studies looking at
RNA stability in post-mortem tissues of poikilothermic fish. Brain,
kidney, liver and muscle were collected from Atlantic salmon (Salmo
salar) parr and samples of each tissue were placed into RNAlatertrade
mark after 0-24 h post-mortem storage at room temperature. Electrophoretic
analysis of the total RNA showed degradation of ribosomal RNA only
in muscle from 8 h onwards. Probing of northern blots with beta-actin
showed that, in the brain, beta-actin mRNA was stable for 24 h post-mortem
but degradation of mRNA was observed after 8 h with the kidney and
liver and after 4 h with the muscle. Expression of the weakly expressed
thyroid hormone receptor beta (TRbeta) was detected by reverse transcriptase
polymerase chain reaction (RT-PCR) in all tissues up to 24 h post-mortem
although a reduction in PCR product was observed after 8 h with muscle
and 24 h with kidney. Analysis with an Agilent 2100 Bioanalyzer showed
that the RNA integrity number (RIN) of brain total RNA remained constant
for 8 h post-mortem with only a small fall at 24 h post-mortem. The
RINs of the remaining tissues indicated degradation at 8 h post-mortem
with kidney and muscle and at 24 hours post-mortem with liver. Taken
together these findings show that degradation of Atlantic salmon
RNA is tissue dependent but stable for at least one hour post-mortem.},
url = {http://www.springerlink.com/content/6p3014817602253q/}
}
@ARTICLE{Seekallu2010,
author = {Seekallu, Srinivas V and Toosi, Behzad M and Grazul-Bilska, Anna
T and Rawlings, Norman C},
title = {Markers of ovarian antral follicular development in sheep: comparison
of follicles destined to ovulate from the final or penultimate follicular
wave of the estrous cycle},
journal = {Reproduction},
year = {2010},
volume = {140},
pages = {559--568},
number = {4},
month = oct,
abstract = {Treatment of non-prolific western white-faced ewes with prostaglandin
F2{alpha} (PGF2{alpha}) and medroxyprogesterone acetate (MAP) increases
the ovulation rate as a result of ovulations from the penultimate
wave in addition to the final wave of the cycle. The objective of
the current study was to evaluate the expression of markers of vascularization/angiogenesis,
a marker of intercellular communication, and cellular proliferation
and apoptosis in follicles from the penultimate and final waves.
On day 8 of the estrous cycle, 15 ewes were administered a single
injection of PGF2{alpha} and an intravaginal MAP sponge, which remained
in place for 6 days. Two days after sponge removal, ovaries which
contained follicles from the penultimate and final waves were collected
and processed for immunohistochemistry followed by image analysis,
and for quantitative real-time RT-PCR. Expression of factor VIII
(marker of vascularization), proliferating cell nuclear antigen,
and GJA1 (Cx43; marker of gap junctional communication) was greater
(P<0.05) in follicles from the final wave compared with follicles
from the penultimate wave. For theca cells, mRNA expression for vascular
endothelial growth factor (VEGF) was greater (P<0.05) and tended
to be greater (P[≤]0.1 and [≥]0.05) for GJA1 and endothelial
nitric oxide synthase in follicles from the final wave compared with
follicles from the penultimate wave. For granulosa cells, the mRNA
expression for GJA1 was greater (P<0.05) and tended to be greater
(P[≤]0.1 and [≥]0.05) for VEGF in follicles from the final
wave compared with follicles from the penultimate wave. In conclusion,
extension of the lifespan of follicles in the penultimate wave reduces
follicular viability in the ewe.},
url = {http://www.reproduction-online.org/cgi/content/abstract/140/4/559}
}
@ARTICLE{Seelan2008,
author = {Seelan, R.S. and Khalyfa, A. and Lakshmanan, J. and Casanova, M.F.
and Parthasarathy, R.N.},
title = {Deciphering the lithium transcriptome: Microarray profiling of lithium-modulated
gene expression in human neuronal cells},
journal = {Neuroscience},
year = {2008},
volume = {151},
pages = {1184--1197},
number = {4},
month = feb,
abstract = {The mechanisms underlying lithium's therapeutic efficacy in the chronic
treatment of bipolar disorder are not clearly understood. Useful
insights can be obtained by identifying genes that are differentially
regulated during chronic lithium treatment. Toward this end, we have
used microarray technology to identify mRNAs that are differentially
expressed in a human neuronal cell line that has been continuously
maintained in therapeutic levels of lithium for 33 days. Significantly,
unlike other transcriptomes where predominantly rodent cells were
used and a limited number of genes probed, we have used human cells
probed with more extensive 44,000 gene microarrays. A total of 671
differentially regulated transcripts, after correcting for false
discovery rates, were identified, of which 347 and 324, respectively,
were found to be up- and downregulated. Peroxiredoxin 2 (PRDX2),
an antioxidant enzyme, was the most upregulated while tribbles homolog
3 (TRB3), a pro-apoptotic protein, was the most downregulated, implying
a beneficial effect of lithium on neuronal cells. Several of the
most highly regulated genes are novel, uncharacterized and encode
proteins of unknown function. Differentially expressed genes associated
with phosphoinositide metabolism include those encoding phosphatidyl
inositol 4-phosphate 5-kinase type II [alpha] (PIP5K2A), WD repeat
domain, phosphoinositide interacting 1 protein (WIPI49), tribbles
homolog 3 (TRB3) and sorting nexin 14 (SNX14). A protein interactome
using some of the saliently regulated genes identified protein kinase
C (PKC) as a major target for lithium action while a global analysis
of all 671 differentially expressed genes identified the mitogen-activated
protein kinase pathway as the most regulated. The list of highly
regulated genes, besides encoding putative targets for antimanic
agents, should prove useful in defining novel pathways, or to better
understand the mechanisms, underlying the mood stabilization process.},
issn = {0306-4522},
keywords = {autophagy, bipolar disorder, inositol, lithium response element, PRDX2,
TRB3},
url = {http://www.sciencedirect.com/science/article/B6T0F-4R466JR-6/2/f0ed14e018e28f96fcad58d289b3b8b4}
}
@ARTICLE{Seewald2009,
author = {Seewald, Michael J. and Ellinghaus, Peter and Kassner, Astrid and
Stork, Ines and Barg, Martina and Niebrugge, Sylvia and Golz, Stefan
and Summer, Holger and Zweigerdt, Robert and Schrader, Eva-Maria
and Feicht, Samantha and Jaquet, Kornelia and Reis, Stephanie and
Korfer, Reiner and Milting, Hendrik},
title = {Genomic profiling of developing cardiomyocytes from recombinant murine
embryonic stem cells reveals regulation of transcription factor clusters},
journal = {Physiol Genomics},
year = {2009},
volume = {38},
pages = {7--15},
number = {1},
month = jun,
abstract = {Cardiomyocytes derived from pluripotent embryonic stem cells (ESC)
have the advantage of providing a source for standardized cell cultures.
However, little is known on the regulation of the genome during differentiation
of ESC to cardiomyocytes. Here, we characterize the transcriptome
of the mouse ESC line CM7/1 during differentiation into beating cardiomyocytes
and compare the gene expression profiles with those from primary
adult murine cardiomyocytes and left ventricular myocardium. We observe
that the cardiac gene expression pattern of fully differentiated
CM7/1-ESC is highly similar to adult primary cardiomyocytes and murine
myocardium, respectively. This finding is underlined by demonstrating
pharmacological effects of catecholamines and endothelin-1 on ESC-derived
cardiomyocytes. Furthermore, we monitor the temporal changes in gene
expression pattern during ESC differentiation with a special focus
on transcription factors involved in cardiomyocyte differentiation.
Thus, CM7/1-ESC-derived cardiomyocytes are a promising new tool for
functional studies of cardiomyocytes in vitro and for the analysis
of the transcription factor network regulating pluripotency and differentiation
to cardiomyocytes.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/38/1/7}
}
@ARTICLE{Segall2010,
author = {Segall, S. K. and Nackley, A. G. and Diatchenko, L. and Lariviere,
W. R. and Lu, X. and Marron, J. S. and Grabowski-Boase, L. and Walker,
J. R. and Slade, G. and Gauthier, J. and Bailey, J. S. and Steffy,
B. M. and Maynard, T. M. and Tarantino, L. M. and Wiltshire, T.},
title = {Comt1 genotype and expression predicts anxiety and nociceptive sensitivity
in inbred strains of mice},
journal = {Genes, Brain and Behavior},
year = {2010},
volume = {9},
pages = {933--946},
number = {8},
abstract = {Catechol-O-methyltransferase (COMT) is a ubiquitously expressed enzyme
that maintains basic biologic functions by inactivating catechol
substrates. In humans, polymorphic variance at the COMT locus has
been associated with modulation of pain sensitivity and risk for
developing psychiatric disorders. A functional haplotype associated
with increased pain sensitivity was shown to result in decreased
COMT activity by altering mRNA secondary structure-dependent protein
translation. However, the exact mechanisms whereby COMT modulates
pain sensitivity and behavior remain unclear and can be further studied
in animal models. We have assessed Comt1 gene expression levels in
multiple brain regions in inbred strains of mice and have discovered
that Comt1 is differentially expressed among the strains, and this
differential expression is cis-regulated. A B2 short interspersed
nuclear element (SINE) was inserted in the 3′-untranslated region
(3′-UTR) of Comt1 in 14 strains generating a common haplotype that
correlates with gene expression. Experiments using mammalian expression
vectors of full-length cDNA clones with and without the SINE element
show that strains with the SINE haplotype (+SINE) have greater Comt1
enzymatic activity. +SINE mice also exhibit behavioral differences
in anxiety assays and decreased pain sensitivity. These results suggest
that a haplotype, defined by a 3′-UTR B2 SINE element, regulates
Comt1 expression and some mouse behaviors.},
issn = {1601-183X},
keywords = {Anxiety, B2 SINE, behavior, COMT1, eQTL, inbred mice, pain},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1601-183X.2010.00633.x}
}
@ARTICLE{Segev2011,
author = {Einat Segev and Yoav Smith and Sigal Ben-Yehuda},
title = {RNA Dynamics in Aging Bacterial Spores},
journal = {Cell},
year = {2011},
pages = { - },
number = {0},
abstract = {Summary Upon starvation, the bacterium Bacillus subtilis enters the
process of sporulation, lasting several hours and culminating in
formation of a spore, the most resilient cell type known. We show
that a few days following sporulation, the RNA profile of spores
is highly dynamic. In aging spores incubated at high temperatures,
RNA content is globally decreased by degradation over several days.
This degradation might be a strategy utilized by the spore to facilitate
its dormancy. However, spores kept at low temperature exhibit a different
RNA profile with evidence supporting transcription. Further, we demonstrate
that germination is affected by spore age, incubation temperature,
and RNA state, implying that spores can acquire dissimilar characteristics
at a time they are considered dormant. We propose that, in contrast
to current thinking, entering dormancy lasts a few days, during which
spores are affected by the environment and undergo corresponding
molecular changes influencing their emergence from quiescence.},
doi = {10.1016/j.cell.2011.11.059},
issn = {0092-8674},
url = {http://www.sciencedirect.com/science/article/pii/S0092867411015108}
}
@ARTICLE{Segovia-Silvestre2011,
author = {Segovia-Silvestre, Toni and Bonnefond, Caroline and Sondergaard,
Bodil and Christensen, Tjorbjoern and Karsdal, Morten and Bay-Jensen,
Anne},
title = {Identification of the calcitonin receptor in osteoarthritic chondrocytes},
journal = {BMC Research Notes},
year = {2011},
volume = {4},
pages = {407},
number = {1},
abstract = {BACKGROUND:Preclinical and clinical studies have shown that salmon
calcitonin has cartilage protective effects in joint degenerative
diseases, such as osteoarthritis (OA). However, the presence of the
calcitonin receptor (CTR) in articular cartilage chondrocytes is
yet to be identified. In this study, we sought to further investigate
the expression of the CTR in naive human OA articular chondrocytes
to gain further confirmation of the existents of the CTR in articular
cartilage.METHODS:Total RNA was purified from primary chondrocytes
from articular cartilage biopsies from four OA patients undergoing
total knee replacement. High quality cDNA was produced using a dedicated
reverse transcription polymerase chain reaction (RT-PCR) protocol.
From this a nested PCR assay amplifying the full coding region of
the CTR mRNA was completed. Western blotting and immunohistochemistry
were used to characterize CTR protein on protein level in chondrocytes.RESULTS:The
full coding transcript of the CTR isoform 2 was identified in all
four individuals. DNA sequencing revealed a number of allelic variants
of the gene including two potentially novel polymorphisms: a frame
shift mutation, +473del, producing a shorter form of the receptor
protein, and a single nucleotide polymorphism in the 3' non coding
region of the transcript, +1443 C>T. A 53 kDa protein band, consistent
with non-glycosylated CTR isoform 2, was detected in chondrocytes
with a similar size to that expressed in osteoclasts. Moreover the
CTR was identified in the plasma membrane and the chondrocyte lacuna
of both primary chondrocytes and OA cartilage section.CONCLUSIONS:Human
OA articular cartilage chondrocytes do indeed express the CTR, which
makes the articular a pharmacological target of salmon calcitonin.
In addition, the results support previous findings suggesting that
calcitonin has a direct anabolic effect on articular cartilage.},
doi = {10.1186/1756-0500-4-407},
issn = {1756-0500},
pubmedid = {21996094},
url = {http://www.biomedcentral.com/1756-0500/4/407}
}
@ARTICLE{Segrelles2008,
author = {Segrelles, Carmen and Moral, Marta and Lorz, Corina and Santos, Mirentxu
and Lu, Jerry and Cascallana, Jose Luis and Lara, M. Fernanda and
Carbajal, Steve and Martinez-Cruz, Ana Belen and Garcia-Escudero,
Ramon and Beltran, Linda and Segovia, Jose C. and Bravo, Ana and
DiGiovanni, John and Paramio, Jesus M.},
title = {Constitutively Active Akt Induces Ectodermal Defects and Impaired
Bone Morphogenetic Protein Signaling},
journal = {Mol. Biol. Cell},
year = {2008},
volume = {19},
pages = {137--149},
number = {1},
month = jan,
abstract = {Aberrant activation of the Akt pathway has been implicated in several
human pathologies including cancer. However, current knowledge on
the involvement of Akt signaling in development is limited. Previous
data have suggested that Akt-mediated signaling may be an essential
mediator of epidermal homeostasis through cell autonomous and noncell
autonomous mechanisms. Here we report the developmental consequences
of deregulated Akt activity in the basal layer of stratified epithelia,
mediated by the expression of a constitutively active Akt1 (myrAkt)
in transgenic mice. Contrary to mice overexpressing wild-type Akt1
(Aktwt), these myrAkt mice display, in a dose-dependent manner, altered
development of ectodermally derived organs such as hair, teeth, nails,
and epidermal glands. To identify the possible molecular mechanisms
underlying these alterations, gene profiling approaches were used.
We demonstrate that constitutive Akt activity disturbs the bone morphogenetic
protein-dependent signaling pathway. In addition, these mice also
display alterations in adult epidermal stem cells. Collectively,
we show that epithelial tissue development and homeostasis is dependent
on proper regulation of Akt expression and activity.},
url = {http://www.molbiolcell.org/cgi/content/abstract/19/1/137}
}
@ARTICLE{Segui2011,
author = {Segui, N and Stevens, K N and Guino, E and Rozek, L S and Moreno,
V R and Capella, G and Gruber, S B and Valle, L},
title = {No association between germline allele-specific expression of TGFBR1
and colorectal cancer risk in Caucasian and Ashkenazi populations},
journal = {Br J Cancer},
year = {2011},
volume = {104},
pages = {735--740},
number = {4},
month = feb,
issn = {0007-0920},
publisher = {Cancer Research UK},
url = {http://dx.doi.org/10.1038/sj.bjc.6606079}
}
@ARTICLE{Seguin2005,
author = {Seguin, Beatrice and Boutros, Paul C. and Li, Xujian and Okey, Allan
B. and Uetrecht, Jack P.},
title = {Gene Expression Profiling in a Model of d-Penicillamine-Induced Autoimmunity
in the Brown Norway Rat: Predictive Value of Early Signs of Danger},
journal = {Chemical Research in Toxicology},
year = {2005},
volume = {18},
pages = {1193-1202},
number = {8},
note = {PMID: 16097792},
doi = {10.1021/tx050040m},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx050040m},
url = {http://pubs.acs.org/doi/abs/10.1021/tx050040m}
}
@ARTICLE{Sehat2010,
author = {Sehat, Bita and Tofigh, Ali and Lin, Yingbo and Trocme, Eric and
Liljedahl, Ulrika and Lagergren, Jens and Larsson, Olle},
title = {SUMOylation Mediates the Nuclear Translocation and Signaling of the
IGF-1 Receptor},
journal = {Sci. Signal.},
year = {2010},
volume = {3},
pages = {ra10--},
number = {108},
month = feb,
url = {http://stke.sciencemag.org/cgi/content/abstract/sigtrans;3/108/ra10}
}
@ARTICLE{Sehic2009,
author = {Sehic, Amer and Khuu, Cuong and Risnes, Steinar and Osmundsen, Harald},
title = {Differential gene expression profiling of the molar tooth germ in
peroxisome proliferator-activated receptor-α (PPAR-α) knockout
mouse and in wild-type mouse: molar tooth phenotype of PPAR-α knockout
mouse},
journal = {European Journal of Oral Sciences},
year = {2009},
volume = {117},
pages = {93--104},
number = {2},
abstract = {Gene expression profiling of the first molar tooth germ at embryonic
days (E)17.5 and 18.5, and at postnatal days (P)0, 2, and 6 from
peroxisome proliferator-activated receptor-α (PPAR-α) knockout
mouse and from wild-type mouse was carried out using microarrays
and validated using real-time reverse transcription–polymerase
chain reaction (RT-PCR) and western blotting. When comparing expression
profiles at each time-point, a total of 1,235 genes showed significantly
different expression, 772 of which exhibited significantly decreased
expression in tooth germ from knockout mouse. With genes exhibiting
significantly decreased levels of expression in tooth germ from PPAR-α
knockout mouse, bioinformatic analysis using ingenuity pathway analysis
yielded significant associations to cellular functions related to
cellular growth/proliferation and to networks related to regulation
of calcium homeostasis. Using scanning electron microscopy to investigate
molars from adult PPAR-α knockout mouse, the molar size was found
to be slightly reduced, the enamel structure was found to be normal,
but cervical molar enamel exhibited evidence suggesting hypomineralization.
Although the PPAR-α knockout had no significant effect on molar
morphology, the results suggest that active PPAR-α signaling is
required to achieve normal mineralization of molar enamel, most probably
through regulation of calcium homeostasis and metabolism of vitamin
D. Cyp27b1 was expressed in tooth germ, suggesting that tooth germ
can synthesize active vitamin D. Expression of Cyp27b1 was significantly
enhanced in postnatal PPAR-α knockout tooth germ.},
issn = {1600-0722},
keywords = {Ambn, Amelx, Calb1, Cyp27b1, vitamin D},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0722.2009.00615.x}
}
@ARTICLE{Sehic2010,
author = {Sehic, Amer and Risnes, Steinar and Khan, Qalb-E-Saleem and Khuu,
Cuong and Osmundsen, Harald},
title = {Gene expression and dental enamel structure in developing mouse incisor},
journal = {European Journal of Oral Sciences},
year = {2010},
volume = {118},
pages = {118--130},
number = {2},
abstract = {Sehic A, Risnes S, Khan Q-E-S, Khuu C, Osmundsen H. Gene expression
and dental enamel structure in developing mouse incisor. Eur J Oral
Sci 2010; 118: 118–130. © 2010 The Authors. Journal compilation
© 2010 Eur J Oral Sci At the mouse incisor tip the initially differentiated
ameloblasts produce a thin, prism-free enamel, while further apically,
in the immediate adjacent segment, the enamel thickness increases
and the four-layered enamel of mouse incisor is formed. Comparative
gene-expression profiling was carried out on RNA isolated from these
two segments of incisor tooth germs at embryonic day (E)17.5 and
at postnatal days (P)0, 1, 2, and 10 using microarrays to measure
messenger RNA (mRNA) and microRNA (miRNA) species present in the
segments. Validation of expression data was achieved using real-time
reverse transcription–polymerase chain reaction (RT-PCR) and western
blotting. Bioinformatic data suggested enhanced cellular apoptosis
in the incisal tip segment, which, together with diminished expression
of the Amelx and Enam genes, may contribute to the production of
the thin enamel seen in this tooth segment. For genes exhibiting
higher levels of expression in the adjacent segment where complex
enamel is being formed, bioinformatic analysis suggested significant
associations with cellular functions involving the actin cytoskeleton,
cellular development, morphology, and movement. This is suggested
to reflect that ameloblasts with Tomes’ process are being organized
in transverse rows, facilitating the transverse movement that results
in prism decussation in the inner enamel of the adjacent segment.
Bioinformatic analysis of miRNA expression data lends support to
these suggestions.},
issn = {1600-0722},
keywords = {actin, ameloblast, Amelx, Enam, microRNA (miRNA)},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0722.2010.00722.x}
}
@ARTICLE{Sehic2011,
author = {Sehic, Amer and Risnes, Steinar and Khuu, Cuong and Khan, Qalb-E-Saleem
and Osmundsen, Harald},
title = {Effects of in vivo transfection with anti-miR-214 on gene expression
in murine molar tooth germ},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {488--498},
number = {9},
month = may,
abstract = {MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that are
believed to be important in many biological processes through regulation
of gene expression. Little is known of their function in tooth morphogenesis
and differentiation. MicroRNA-214 (miR-214), encoded by the polycistronic
Dnm30os gene, is highly expressed during development of molar tooth
germ and was selected as a target for silencing with anti-miR-214.
Mandibular injection of 1-100 pmol of anti-miR-214 close to the developing
first molar in newborn mice resulted in significant decrease in expression
of miR-214, miR-466h, and miR-574-5p in the tooth germ. Furthermore,
levels of miR-199a-3p, miR-199a-5p, miR-690, miR-720, and miR-1224
were significantly increased. Additionally, the expression of 863
genes was significantly increased and the expression of 305 genes
was significantly decreased. Among the genes with increased expression
was Twist-1 and Ezh2, suggested to regulate expression of miR-214.
Microarray results were validated using real-time RT-PCR and Western
blotting. Among genes with decreased expression were Amelx, Calb1,
Enam, and Prnp; these changes also being reflected in levels of corresponding
encoded proteins in the tooth germ. In the anti-miR-214-treated molars
the enamel exhibited evidence of hypomineralization with remnants
of organic material and reduced surface roughness after acid etching,
possibly due to the transiently decreased expression of Amelx and
Enam. In contrast, several genes encoding contractile proteins exhibited
significantly increased expression. mRNAs involved in amelogenesis
(Ambn, Amelx, Enam) were not found among targets of miRNAs that were
differentially expressed following treatment with anti-miR-214. It
is therefore suggested that effects of miR-214 on amelogenesis are
indirect, perhaps mediated by the observed miR-214-dependent changes
in levels of expression of numerous transcription factors.},
comment = {10.1152/physiolgenomics.00248.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/9/488}
}
@ARTICLE{Sehm2005,
author = {Sehm, Julia and Polster, Jurgen and Pfaffl, Michael W.},
title = {Effects of Varied EGCG and (+)-Catechin Concentrations on Proinflammatory
Cytokines mRNA Expression in ConA-Stimulated Primary White Blood
Cell Cultures},
journal = {Journal of Agricultural and Food Chemistry},
year = {2005},
volume = {53},
pages = {6907-6911},
number = {17},
note = {PMID: 16104819},
doi = {10.1021/jf0503107},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf0503107},
url = {http://pubs.acs.org/doi/abs/10.1021/jf0503107}
}
@ARTICLE{Seidel2006,
author = {Seidel, Shawn D. and Hung, Shao-Ching and Lynn Kan, H and Bhaskar
Gollapudi, B},
title = {Background Gene Expression in Rat Kidney: Influence of Strain, Gender,
and Diet},
journal = {Toxicol. Sci.},
year = {2006},
volume = {94},
pages = {226--233},
number = {1},
month = nov,
abstract = {In order to gain better insight into factors (strain, gender, and
diet) influencing background variability in kidney gene expression,
we examined the transcriptomes of male and female Crl:CD(SD)IGSBR
(Sprague-Dawley [SD]) and CDF(Fischer 344)/CrlBR rats maintained
for 19 days on three different diets (ad libitum [AL], diet restriction--75%
of AL, and casein-based phytoestrogen-free diet). Kidney RNA was
analyzed using Agilent Rat oligo microarrays (approximately 20,000
genes). Principal component analysis demonstrated that strain and
gender have the most impact on the variability in gene expression,
while diet had a lesser effect. The majority of the affected genes
differed by a magnitude of four-fold or less between strains/gender,
with some previously known to be sex-hormone regulated (SLC22A7 and
SLC21A1). One gene of particular interest was ornithine decarboxylase,
a significant marker of cell proliferation and tumor promotion, which
was expressed at an 18-fold greater level in SD rats. Further analysis
revealed that the difference in expression was due to the use of
an alternate polyadenylation signal resulting in the production of
two different sizes of transcripts. These results demonstrate that
gender and strain have significant influence on gene expression which
could be a confounder when comparing results, especially when it
involves predictive fingerprint/patterns.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/94/1/226}
}
@ARTICLE{Seidl2007,
author = {Seidl, Hannes and Richtig, Erika and Tilz, Hemma and Stefan, Martina
and Schmidbauer, Ulrike and Asslaber, Martin and Zatloukal, Kurt
and Herlyn, Meenhard and Schaider, Helmut},
title = {Profiles of chemokine receptors in melanocytic lesions: de novo expression
of CXCR6 in melanoma},
journal = {Human Pathology},
year = {2007},
volume = {38},
pages = {768--780},
number = {5},
month = may,
abstract = {Summary Selective expression of certain chemokine receptors by melanoma
cells and the presence of their ligands in tissues might govern organ
site-specific metastasis. Because the expression profile of chemokine
receptors in tissues of melanocytic origin is unknown, we performed
a comprehensive study on melanocytic tissue samples investigating
the expression of 18 chemokine receptors at the mRNA level by real-time
polymerase chain reaction, using a semiquantitative approach, and
of 3 chemokine receptors (CXCR6, CCR9, and XCR1) at the protein level.
We report on the de novo expression of CXCR6 in primary melanomas
and melanoma metastases, but absence in melanoma cell lines and congenital
nevi. CXCR4 and CCR1 were the only 2 chemokine receptors that were
consistently expressed in melanocytes, melanoma cell lines, primary,
and metastatic melanoma; CCR1 expression increased significantly
over progression. CCR9 and XCR1 transcripts were found in melanocytic
lesions, and expression was confirmed by immunohistochemistry. Transcripts
for CCR10 were not found in any of the lesions, but in some melanoma
cell lines. Expression of CCR7 was observed in primary melanomas
and some metastases. CCR5 was exclusively expressed in primary melanomas
and some cutaneous metastases. Results revealed a restricted and
differential pattern of chemokine receptor expression in melanoma
tissue, which varies substantially from the expression profile of
melanoma cell lines and warrants functional studies on some receptors.},
issn = {0046-8177},
keywords = {Chemokine, Chemokine receptor, Malignant melanoma, Tumor progression,
CXCR6},
url = {http://www.sciencedirect.com/science/article/B6WGD-4N2DRF9-9/2/e32225aac1640cf1d920e14472f0c97c}
}
@ARTICLE{Seierstad2009,
author = {Seierstad, Sverre L. and Haugland, Øyvind and Larsen, Stig and Waagbø,
Rune and Evensen, Øystein},
title = {Pro-inflammatory cytokine expression and respiratory burst activity
following replacement of fish oil with rapeseed oil in the feed for
Atlantic salmon (Salmo salar L.)},
journal = {Aquaculture},
year = {2009},
volume = {289},
pages = {212--218},
number = {3-4},
month = apr,
abstract = {The objective of the present study was to elucidate if modulation
of membrane lipids after replacement of fish oil with rapeseed oil
in the feed, influences pro-inflammatory cytokine expression and
respiratory burst activity. As immune responses of fish show high
degree of individual variation an ex vivo plasma incubation model
was used. Head kidney leukocytes isolated from salmon fed a commercial
diet were incubated for 20 h in diluted plasma obtained from three
groups of adult salmon fed different dietary lipid sources, fish
oil (FO), rapeseed oil (RO), or their 1:1 blend (FO/RO). Plasma obtained
from the feeding studies reflected the fatty acid composition of
the diets with an n-3/n-6 ratio for the FO, FO/RO and RO groups of
13.6, 6.8, and 2.1 respectively. Fatty acid profiles of incubated
leukocytes mirrored the plasma composition with step wise changes
in major fatty acids. Gene expression of TNF-[alpha] and IL-1[beta]
increased significantly in all groups over the 12 h study period
following LPS stimulation. However, there was no significant difference
in expression of the cytokines between the three lipid groups. Similarly,
there were no differences in respiratory burst response between the
lipid groups. A 5-fold reduction in n-3/n-6 fatty acid ratio did
not change said pro-inflammatory cytokines or the respiratory burst
responses following stimulation. Despite a marked change in n-3/n-6
ratio in leukocyte membranes following plasma incubation, there were
less marked alterations in arachidonic acid (AA) and eicosapentaenoic
acid (EPA), key players in modulating phagocyte responses as precursors
to eicosanoid synthesis. This might provide an explanation to the
lack of influence of fatty acid sources on inflammatory responses
in the leukocytes.},
issn = {0044-8486},
keywords = {Membrane lipid modulation, Leukocytes, Cytokine expression, Respiratory
burst, Atlantic salmon},
url = {http://www.sciencedirect.com/science/article/B6T4D-4V59VV5-6/2/11383888b7b5e28789a26cc1c364701f}
}
@ARTICLE{Seiffert2010,
author = {Seiffert, Martina and Schulz, Angela and Ohl, Sibylle and Dohner,
Hartmut and Stilgenbauer, Stephan and Lichter, Peter},
title = {Soluble CD14 is a novel monocyte-derived survival factor for chronic
lymphocytic leukemia cells, which is induced by CLL cells in vitro
and present at abnormally high levels in vivo},
journal = {Blood},
year = {2010},
volume = {116},
pages = {4223--4230},
number = {20},
month = nov,
abstract = {Accumulation of leukemic cells in patients with chronic lymphocytic
leukemia (CLL) is due to prolonged cell survival rather than increased
proliferation. Survival of CLL cells depends on microenvironmental
factors. Even though long-lived in vivo, CLL cells rapidly die by
spontaneous apoptosis in vitro unless cocultured with stromal cells
or their conditioned medium. In the present study, we show that survival
of CLL cells is maintained in high cell density cultures, where the
main prosurvival activity is delivered by monocytes. Cytokine array
and enzyme-linked immunosorbent assay studies revealed increased
expression of soluble CD14 by monocytes in the presence of CLL cells.
The addition of recombinant soluble CD14 to primary CLL cells resulted
in significantly increased cell survival rates, which were associated
with higher activity nuclear factor {kappa}B. Quantification of serum
levels of soluble CD14 revealed abnormally high levels of this protein
in CLL patients, indicating a potential role of soluble CD14 in vivo.
In summary, the presented data show that monocytes help in the survival
of CLL cells by secreting soluble CD14, which induces nuclear factor
{kappa}B activation in these cells, and that CLL cells actively shape
their microenvironment by inducing CD14 secretion in accessory monocytes.},
comment = {10.1182/blood-2010-05-284505},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/116/20/4223}
}
@ARTICLE{Seiler2003,
author = {Seiler, Peter and Aichele, Peter and Bandermann, Silke and Hauser,
Anja E. and Lu, Bao and Gerard, Norma P. and Gerard, Craig and
Ehlers, Stefan and Mollenkopf, Hans J. and Kaufmann, Stefan H. E.},
title = {Early granuloma formation after aerosol Mycobacterium tuberculosis
infection is regulated by neutrophils via CXCR3-signaling chemokines},
journal = {Eur. J. Immunol.},
year = {2003},
volume = {33},
pages = {2676--2686},
number = {10},
abstract = {Abstract 10.1002/eji.200323956.abs Among the first cells to invade
a site of infection, polymorphonuclear neutrophils (PMN) play an
important role in the control of numerous infections. While PMN are
considered critical for control of acute infections, their role in
chronic infections remains less well understood. Here we report that
PMN are essential for accurate early granuloma formation during chronic
M. tuberculosis infection without influencing mycobacterial growth
restriction. The PMN-mediated regulation of granuloma formation depended
on chemokines signaling through CXCR3, in particular MIG, as indicated
by immune histochemical analysis of lung sections from C57BL/6 wild-type
and CXCR3–/– mutant mice and supported by microarray transcriptome
analysis. Hence, PMN play a central role in regulating the focal
granulomatous response in the lung, and this early granuloma formation
can be segregated from long-term protection against pulmonary M.
tuberculosis infection.},
issn = {1521-4141},
keywords = {Neutrophils, CXCR3, Mycobacterium tuberculosis, Granuloma},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200323956}
}
@ARTICLE{Seiser2011,
author = {Seiser, E. L. and Thomas, R. and Richards, K. L. and Kathryn Kelley,
M. and Moore, P. and Suter, S. E. and Breen, M.},
title = {Reading between the lines: molecular characterization of five widely
used canine lymphoid tumour cell lines},
journal = {Veterinary and Comparative Oncology},
year = {2011},
pages = {no--no},
abstract = {Molecular characterization of tumour cell lines is increasingly regarded
as a prerequisite for defining their validity as models of in vivo
neoplasia. We present the first comprehensive catalogue of genomic
and transcriptional characteristics of five widely used canine lymphoid
tumour cell lines. High-resolution microarray-based comparative genomic
hybridization defined their unique profiles of genomic DNA copy number
imbalance. Multicolour fluorescence in situ hybridization identified
aberrant gains of MYC, KIT and FLT3 and deletions of PTEN and CDKN2
in individual cell lines, and also revealed examples of extensive
structural chromosome reorganization. Gene expression profiling and
RT-PCR analyses defined the relationship between genomic imbalance
and transcriptional dysregulation in each cell line, clarifying their
relevance as models of discrete functional pathways with biological
and therapeutic significance. In combination, these data provide
an extensive resource of molecular data for directing the appropriate
use of these cell lines as tools for studying canine lymphoid neoplasia.},
doi = {10.1111/j.1476-5829.2011.00299.x},
issn = {1476-5829},
keywords = {canine, cell line, comparative, lymphoid neoplasia, microarray, model},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1476-5829.2011.00299.x}
}
@ARTICLE{Seitz2010,
author = {Seitz, Sarah J. and Schleithoff, Elisa Schulze and Koch, Andreas
and Schuster, André and Teufel, Andreas and Staib, Frank and Stremmel,
Wolfgang and Melino, Gerry and Krammer, Peter H. and Schilling, Tobias
and Müller, Martina},
title = {Chemotherapy-induced apoptosis in hepatocellular carcinoma involves
the p53 family and is mediated via the extrinsic and the intrinsic
pathway},
journal = {Int. J. Cancer},
year = {2010},
volume = {126},
pages = {2049--2066},
number = {9},
abstract = {Abstract 10.1002/ijc.24861.abs We investigated the downstream mechanisms
by which chemotherapeutic drugs elicit apoptosis in hepatocellular
carcinoma (HCC). Genomic signatures of HCC cell lines treated with
different chemotherapeutic drugs were obtained. Analyses of apoptosis
pathways were performed and RNA interference was used to evaluate
the role of the p53 family. Endogenous p53, p63 and p73 were upregulated
in response to DNA damage by chemotherapeutic drugs. Blocking p53
family function led to chemoresistance in HCC. Stimulation and blocking
experiments of the CD95-, the TNF- and the TRAIL-receptor systems
revealed that cytotoxic drugs, via the p53 family members as transactivators,
can trigger expression of each of these death receptors and consequently
sensitize HCC cells toward apoptosis. Furthermore, our findings demonstrate
a link between chemotherapy, the p53 family and the mitochondrial
apoptosis pathway in HCC. Chemotherapeutic treatment induces expression
of proapoptotic Bcl-2 family members like Bax and BCL2L11 and the
expression of Apaf1, BNIP1, Pdcd8 and RAD. Thus, upon DNA damage,
p53, p63 and p73 promote apoptosis via the extrinsic and the intrinsic
signaling pathway. In addition, not only proapoptotic genes were
upregulated, but also genes known to exert antiapoptotic functions.
Bleomycin-induced upregulation of BCL-XL/BCLXL1 and MDM2 suggests
that it is the ratio of proapoptotic and antiapoptotic proteins that
regulates the apoptosis response of HCC cells toward chemotherapy,
thereby playing a decisive role between treatment sensitivity vs.
drug resistance. The clinical importance of these data is evidenced
by our finding that the bleomycin target gene signature can predict
the prognosis of patients suffering from HCC.},
issn = {1097-0215},
keywords = {apoptosis, chemosensitivity, p53, p63, p73, CD95, TRAIL},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24861}
}
@ARTICLE{Sekido2008,
author = {Sekido, Takako and Bodelier, Paul L.E. and Shoji, Tadashi and Suwa,
Yuichi and Laanbroek, Hendrikus J.},
title = {Limitations of the use of group-specific primers in real-time PCR
as appear from quantitative analyses of closely related ammonia-oxidising
species},
journal = {Water Research},
year = {2008},
volume = {42},
pages = {1093--1101},
number = {4-5},
month = feb,
abstract = {To study the ecology of ammonia-oxidising bacteria (AOB), quantitative
techniques are essential. Real-time PCR assays based on the 16S rRNA
or on the structural amoA gene are routinely used. The CTO primer
set rooted on the 16S rRNA gene has a number of mismatches with some
of the cultures of AOB. To examine if these mismatches have an effect
on the outcome of real-time PCR assays, the assay was tested with
DNA from a number of closely related isolates of AOB. Standard curves
of known amounts of initial DNA were similar among most of the tested
cultures of AOB, except for the standard curves of Nitrosomonas strain
AL212 and Nitrosospira strain NpAV. Nitrosomonas strain AL212 had
3 mismatches with the CTO primer set. Adaptation of the CTO primer
set in order to perfectly match the Nitrosomonas strain AL212 gave
a standard curve similar to the majority of the AOB tested. As Nitrosospira
strain NpAV has no mismatches with the original CTO primer set, there
must be another reason for the less efficient amplification than
the sequence itself. Application of an existing sigmoidal mathematical
model gave no other results with respect to the standard curves of
Nitrosomonas europaea and Nitrosomonas strain AL212, but also demonstrated
that primer mismatches can seriously underestimate the initial target
concentration. It was concluded that in general correct interpretation
of real-time PCR results requires knowledge of the target community
composition, in particular of the target sequences of the dominant
community members.},
issn = {0043-1354},
keywords = {Nitrosomonas, Nitrosospira, Ammonium oxidation, Quantitative PCR,
Primer mismatch},
url = {http://www.sciencedirect.com/science/article/B6V73-4PKXBMR-9/2/6161410ff4ff952d0820c86beb554a09}
}
@ARTICLE{Sekigawa2009,
author = {Sekigawa, T. and Tajima, A. and Hasegawa, T. and Hasegawa, Y. and
Inoue, H. and Sano, Y. and Matsune, S. and Kurono, Y. and Inoue,
I.},
title = {Gene-expression profiles in human nasal polyp tissues and identification
of genetic susceptibility in aspirin-intolerant asthma},
journal = {Clinical \& Experimental Allergy},
year = {2009},
volume = {39},
pages = {972--981},
number = {7},
abstract = {Summary Background Aspirin-intolerant asthma (AIA) is a subtype of
asthma induced by non-steroidal anti-inflammatory drugs and characterized
by an aggressive mucosal inflammation of the lower airway (asthma)
and the upper airways (rhinitis and nasal polyp). The lower airway
lesion and the nasal polyp in AIA are postulated to have common pathogenic
features involving aspirin sensitivity that would be reflected in
the gene expression profile of AIA polyps. Objective This study was
conducted to clarify the pathogenesis of AIA using gene expression
analysis in nasal polyps, and identify genetic susceptibilities underlying
AIA in a case–control association study. Methods Global gene expression
of nasal polyps from nine AIA patients was examined using microarray
technology in comparison with nasal polyps from five eosinophilic
sinusitis (ES) patients, a related disease lacking aspirin sensitivity.
Based on the AIA-specific gene expression profile of nasal polyp,
candidate genes for AIA susceptibility were selected and screened
by a case–control design of 219 AIA patients, 374 non-asthmatic
control (CTR), and 282 aspirin-tolerant asthmatic (ATA) subjects.
Results One hundred and forty-three elevated and three decreased
genes were identified as AIA-specific genes that were enriched in
immune response according to Gene Ontology analysis. In addition,
a k-means-based algorithm was applied to cluster the genes, and a
subclass characteristic of AIA comprising 18 genes that were also
enriched in immune response was identified. By examining the allelic
associations of single nucleotide polymorphisms (SNPs) of AIA candidate
genes relevant to an immune response with AIA, two SNPs, one each
of INDO and IL1R2, showed significant associations with AIA (P=0.011
and 0.026 after Bonferroni's correction, respectively, in AIA vs.
CTR). In AIA–ATA association analysis, modest associations of the
two SNPs with AIA were observed. Conclusion These results indicate
that INDO and IL1R2, which were identified from gene expression analyses
of nasal polyps in AIA, represent susceptibility genes for AIA.},
issn = {1365-2222},
keywords = {aspirin-intolerant asthma, candidate genes, genetic association, genome-wide
gene expression, single nucleotide polymorphism},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2222.2009.03229.x}
}
@ARTICLE{Sekiguchi2008,
author = {Sekiguchi, N. and Kawauchi, S. and Furuya, T. and Inaba, N. and Matsuda,
K. and Ando, S. and Ogasawara, M. and Aburatani, H. and Kameda, H.
and Amano, K. and Abe, T. and Ito, S. and Takeuchi, T.},
title = {Messenger ribonucleic acid expression profile in peripheral blood
cells from RA patients following treatment with an anti-TNF-{alpha}
monoclonal antibody, infliximab},
journal = {Rheumatology},
year = {2008},
volume = {47},
pages = {780--788},
number = {6},
month = jun,
abstract = {Objectives. We monitored the mRNA expression profiles of peripheral
blood cells during treatment with a TNF-{alpha} inhibitor, infliximab,
in patients with RA. Using a DNA microarray analysis, we demonstrated
a unique set of genes, with distinct baseline and post-treatment
changes in expression between responders and non-responders to infliximab
treatment. Methods. Using a customized low-density cDNA microarray
with 747 genes and a reliable data collection system, we monitored
the mRNA expression profiles of whole blood cells from 18 RA patients
before and after the infusion of infliximab for up to 22 weeks. The
clinical response to treatment with infliximab was determined using
the ACR response criteria, the disease activity score of 28 joints
(DAS28), and individual clinical parameters. The patients were classified
as responders or non-responders based on their ACR50% response at
22 weeks. Results. Approximately 15% of the total genes were found
to exhibit a >1.5-fold change, compared with their reference values,
at one or more time points during the 22 weeks of infliximab therapy.
The expression of inflammatory genes, such as IFN-related genes,
was strongly correlated with the serum level of CRP and the DAS28.
The increased expression of inflammatory genes in responders was
normalized within 2 weeks and then remained at a normal level during
the treatment period. In contrast, in the non-responders, the elevated
expression at baseline, although it was significantly decreased at
2 weeks, returned to the baseline level after 14 weeks. In addition
to inflammatory genes, we identified several groups of genes with
distinct differences in expression between the responders and non-responders.
Conclusions. Our results suggest that a customized low-density microarray
is useful for monitoring mRNA expression profiles in peripheral blood
cells, enabling us to identify a unique set of genes with differentially
regulated expressions in responders and non-responders to a TNF inhibitor
among patients with RA.},
url = {http://rheumatology.oxfordjournals.org/cgi/content/abstract/47/6/780}
}
@ARTICLE{Sekine2011,
author = {Sekine, Yoshitaka and Osei-Hwedieh, David and Matsuda, Kant and Raghavachari,
Nalini and Liu, Delong and Furuya, Yosuke and Koike, Hidekazu and
Suzuki, Kazuhiro and Remaley, Alan T.},
title = {High fat diet reduces the expression of glutathione peroxidase 3
in mouse prostate},
journal = {The Prostate},
year = {2011},
volume = {71},
pages = {1499--1509},
number = {14},
abstract = {BACKGROUNDHigh fat diets are known to be a risk factor for prostate
cancer. In this study, we investigated the effect of high fat diet
on mouse prostate gene expression.METHODSC57BL/6J mice were fed either
a control or high fat diet for 12 weeks. Microarray analyses were
performed on mouse ventral prostate (VP) and dorsolateral prostate
(DLP), followed by canonical pathway analysis and regulatory network
identification. mRNA changes were confirmed by real time PCR.RESULTSApproximately
2,125, and 1,194 genes responded significantly to the high fat diet
in VP, DLP, respectively. Pathways and networks related to oxidative
stress, glutathione metabolism, NRF-mediated oxidative stress response
and NF-kappaB were all differentially regulated by high fat diet.
Glutathione peroxidase 3 (GPx3) mRNA levels were decreased by approximately
twofold by high fat diet in all three prostate lobes. In human non-transformed
prostate cells (PrSC, PrEC, and BPH-1), cholesterol loading decreased
GPx3 expression, and increased H2O2 levels of culture medium. Troglitazone
increased GPx3 expression in three normal prostate cells, and decreased
H2O2 levels. In addition, troglitazone attenuated cholesterol-induced
H2O2 increase. Tissue from prostate cancer biopsies had decreased
GPx3 mRNA and its level was inversely related to the Gleason score.CONCLUSIONSHigh
fat diet alters pathways related to many genes concerned with oxidative
stress. GPx3, a gene identified by this analysis, was found to be
down-regulated by high fat diet and appears be decreased in human
prostate cancers, suggesting that GPx3 may have a possible role in
modulating carcinogenesis. Prostate 71:1499–1509, 2011. © 2011
Wiley-Liss, Inc.},
doi = {10.1002/pros.21365},
issn = {1097-0045},
keywords = {high fat diet, prostate, GPx3, cholesterol, mouse},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.21365}
}
@ARTICLE{Sekkai2005,
author = {Sekkaï, Dalila and Gruel, Gaëtan and Herry, Magali and Moucadel,
Virginie and Constantinescu, Stefan N. and Albagli, Olivier and Roux,
Diana Tronik-Le and Vainchenker, William and Bennaceur-Griscelli,
Annelise},
title = {Microarray Analysis of LIF/Stat3 Transcriptional Targets in Embryonic
Stem Cells},
journal = {STEM CELLS},
year = {2005},
volume = {23},
pages = {1634--1642},
number = {10},
abstract = {Abstract 10.1634/stemcells.2005-0182.abs Mouse embryonic stem (ES)
cells can be propagated in vitro while retaining their properties
of pluripotency and self-renewal under the continuous presence of
leukemia inhibitor factor (LIF). An essential role has been attributed
to subsequent activation of the Stat3 transcription factor in mediating
LIF self-renewal response. To date, however, downstream target genes
of Stat3 in ES cells are still unknown. To isolate these genes, we
performed a microarray-based kinetic comparison of LIF-stimulated
(undifferentiated) ES cells versus ES cells induced to differentiate
by shutting down Stat3 activity through either LIF deprivation or,
more specifically, expression of a Stat3 dominant-negative mutant.
In each case, we chose the earliest time at which ES cells lose their
self-renewal properties, as illustrated by a decrease in the number
of embryoid bodies and blast cell colony formation as well as germ
layer marker expression. Comparison of the two independent approaches
revealed similarly regulated genes that are likely to be involved
in the Stat3 effects on ES cell self-renewal. For instance, upregulation
of growth factors such as the transforming growth factor-β relative
Lefty1 or transcriptional regulators such as Id1 and Id2 and down-regulation
of the groucho-like protein Aes1 (grg5) were found. Promoter analysis
of the aes1 gene revealed three functional Stat3 consensus sites,
as shown by luciferase assays. Furthermore, chromatin immunoprecipitation
experiment demonstrated that Stat3 is recruited to the promoter of
aes1 in ES cells. These data demonstrated that the aes1 gene is a
direct transcriptional target of Stat3 in ES cells.},
issn = {1549-4918},
keywords = {Stat3, Self-renewal, Microarray, Leukemia inhibitor factor, grg5},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2005-0182}
}
@ARTICLE{Sela2008,
author = {Sela, D. A. and Chapman, J. and Adeuya, A. and Kim, J. H. and Chen,
F. and Whitehead, T. R. and Lapidus, A. and Rokhsar, D. S. and Lebrilla,
C. B. and German, J. B. and Price, N. P. and Richardson, P. M. and
Mills, D. A.},
title = {The genome sequence of Bifidobacterium longum subsp. infantis reveals
adaptations for milk utilization within the infant microbiome},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {18964--18969},
number = {48},
month = dec,
abstract = {Following birth, the breast-fed infant gastrointestinal tract is rapidly
colonized by a microbial consortium often dominated by bifidobacteria.
Accordingly, the complete genome sequence of Bifidobacterium longum
subsp. infantis ATCC15697 reflects a competitive nutrient-utilization
strategy targeting milk-borne molecules which lack a nutritive value
to the neonate. Several chromosomal loci reflect potential adaptation
to the infant host including a 43 kbp cluster encoding catabolic
genes, extracellular solute binding proteins and permeases predicted
to be active on milk oligosaccharides. An examination of in vivo
metabolism has detected the hallmarks of milk oligosaccharide utilization
via the central fermentative pathway using metabolomic and proteomic
approaches. Finally, conservation of gene clusters in multiple isolates
corroborates the genomic mechanism underlying milk utilization for
this infant-associated phylotype.},
url = {http://www.pnas.org/cgi/content/abstract/105/48/18964}
}
@ARTICLE{Selby2011,
author = {Selby, Katja and Lindstrom, Miia and Somervuo, Panu and Heap, John
T. and Minton, Nigel P. and Korkeala, Hannu},
title = {Important Role of Class I Heat Shock Genes hrcA and dnaK in the Heat
Shock Response and the Response to pH and NaCl Stress of Group I
Clostridium botulinum Strain ATCC 3502},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {2823--2830},
number = {9},
month = may,
abstract = {Class I heat shock genes (HSGs) code for molecular chaperones which
play a major role in the bacterial response to sudden increases of
environmental temperature by assisting protein folding. Quantitative
reverse transcriptase real-time PCR gene expression analysis of the
food-borne pathogen Clostridium botulinum grown at 37{degrees}C showed
that the class I HSGs grpE, dnaK, dnaJ, groEL, and groES and their
repressor, hrcA, were expressed at constant levels in the exponential
and transitional growth phases, whereas strong downregulation of
all six genes was observed during stationary phase. After heat shock
from 37 to 45{degrees}C, all HSGs were transiently upregulated. A
mutant with insertionally inactivated hrcA expressed higher levels
of class I HSGs during exponential growth than the wild type, followed
by upregulation of only groES and groES after heat shock. Inactivation
of hrcA or of dnaK encoding a major chaperone resulted in lower maximum
growth temperatures than for the wild type and reduced growth rates
under optimal conditions compared to the wild type. The dnaK mutant
showed growth inhibition under all tested temperature, pH, and NaCl
stress conditions. In contrast, the growth of an hrcA mutant was
unaffected by mild temperature or acid stress compared to the wild-type
strain, indicating that induced class I HSGs support growth under
moderately nonoptimal conditions. We show that the expression of
class I HSGs plays a major role for survival and growth of C. botulinum
under the stressful environmental conditions that may be encountered
during food processing or growth in food products, in the mammalian
intestine, or in wounds.},
comment = {10.1128/AEM.02633-10},
url = {http://aem.asm.org/cgi/content/abstract/77/9/2823}
}
@ARTICLE{Selenius2011,
author = {Selenius, Markus and Hedman, Mattias and Brodin, David and Gandin,
Valentina and Rigobello, Maria Pia and Flygare, Jenny and Marzano,
Christine and Bindoli, Alberto and Brodin, Ola and Björnstedt, Mikael
and Fernandes, Aristi P},
title = {Effects of redox modulation by inhibition of Thioredoxin reductase
on radiosensitivity and gene expression},
journal = {Journal of Cellular and Molecular Medicine},
year = {2011},
pages = {no--no},
abstract = {The thioredoxin system is a promising target when aiming to overcome
the problem of clinical radiation resistance. Altered cellular redox-status
and redox sensitive thiols contributing to induction of resistance
strongly connects the ubiquitous redox enzyme thioredoxin reductase
to the cellular response to ionizing radiation. To further investigate
possible strategies in combating clinical radiation resistance, human
radio-resistant lung cancer cells were subjected to a combination
of single fractions of γ-radiation at clinically relevant doses
and non-toxic levels of a well-characterized thioredoxin reductase
(TrxR) inhibitor, the phosphine gold(I) compound [Au(SCN)(PEt3)].
The combination of the TrxR-inhibitor and ionizing radiation reduced
the surviving fractions and impaired the ability of the U1810 cells
to repopulate by approximately 50%. In addition, inhibition of thioredoxin
reductase caused changes in the cell cycle distribution, suggesting
a disturbance of the mitotic process. Global gene expression analysis
also revealed clustered genetic expression changes connected to several
major cellular pathways such as cell cycle, cellular response to
stress and DNA-damage. Specific TrxR-inhibition as a factor behind
the achieved results was confirmed by correlation of gene expression
patterns between gold and siRNA treatment. These results clearly
demonstrates TrxR as an important factor conferring resistance to
irradiation and the use of [Au(SCN)(PEt3)] as a promising radiosensitizing
agent.},
doi = {10.1111/j.1582-4934.2011.01469.x},
issn = {1582-4934},
keywords = {ionizing radiation, radiation resistance, lung cancer, Thioredoxin
reductase, radiosensitizer},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2011.01469.x}
}
@ARTICLE{Selga2011,
author = {Selga, Elisabet and Pérez-Cano, Francisco and Franch, Àngels and
Ramírez-Santana, Carolina and Rivero, Montserrat and Ciudad, Carlos
and Castellote, Cristina and Noé, Véronique},
title = {Gene expression profiles in rat mesenteric lymph nodes upon supplementation
with Conjugated Linoleic Acid during gestation and suckling},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {182},
number = {1},
abstract = {BACKGROUND:Diet plays a role on the development of the immune system,
and polyunsaturated fatty acids can modulate the expression of a
variety of genes. Human milk contains conjugated linoleic acid (CLA),
a fatty acid that seems to contribute to immune development. Indeed,
recent studies carried out in our group in suckling animals have
shown that the immune function is enhanced after feeding them with
an 80:20 isomer mix composed of c9,t11 and t10,c12 CLA. However,
little work has been done on the effects of CLA on gene expression,
and even less regarding immune system development in early life.RESULTS:The
expression profile of mesenteric lymph nodes from animals supplemented
with CLA during gestation and suckling through dam's milk (Group
A) or by oral gavage (Group B), supplemented just during suckling
(Group C) and control animals (Group D) was determined with the aid
of the specific GeneChip® Rat Genome 230 2.0 (Affymettrix). Bioinformatics
analyses were performed using the GeneSpring GX software package
v10.0.2 and lead to the identification of 89 genes differentially
expressed in all three dietary approaches. Generation of a biological
association network evidenced several genes, such as connective tissue
growth factor (Ctgf), tissue inhibitor of metalloproteinase 1 (Timp1),
galanin (Gal), synaptotagmin 1 (Syt1), growth factor receptor bound
protein 2 (Grb2), actin gamma 2 (Actg2) and smooth muscle alpha actin
(Acta2), as highly interconnected nodes of the resulting network.
Gene underexpression was confirmed by Real-Time RT-PCR.CONCLUSIONS:Ctgf,
Timp1, Gal and Syt1, among others, are genes modulated by CLA supplementation
that may have a role on mucosal immune responses in early life.},
doi = {10.1186/1471-2164-12-182},
issn = {1471-2164},
pubmedid = {21481241},
url = {http://www.biomedcentral.com/1471-2164/12/182}
}
@ARTICLE{Selgrade2006,
author = {Selgrade, MaryJaneK and Boykin, Elizabeth H. and Haykal-Coates, Najwa
and Woolhiser, Michael R. and Wiescinski, Connie and Andrews, Debora
L. and Farraj, Aimen K. and Doerfler, Donald L. and Gavett, Stephen
H.},
title = {Inconsistencies between Cytokine Profiles, Antibody Responses, and
Respiratory Hyperresponsiveness following Dermal Exposure to Isocyanates},
journal = {Toxicol. Sci.},
year = {2006},
volume = {94},
pages = {108--117},
number = {1},
month = nov,
abstract = {Cytokine profiling of local lymph node responses has been proposed
as a simple test to identify chemicals, such as low molecular weight
diisocyanates, that pose a significant risk of occupational asthma.
Previously, we reported cytokine messenger RNA (mRNA) profiles for
dinitrochlorobenzene (DNCB) and six isocyanates: toluene diisocyanate,
diphenylmethane-4,4'-diisocyanate, dicyclohexylmethane-4,4'-diisocyanate,
isophorone diisocyanate, p-tolyl(mono)isocyanate, and meta-tetramethylene
xylene diisocyanate. The present study was conducted to test the
hypothesis that relative differences in the cytokine profile are
predictive of relative differences in total serum immunoglobulin
(Ig) E and respiratory responses to methacholine (Mch) following
dermal exposure to the chemicals. After a preliminary experiment
to determine an exposure regimen sufficient to achieve responses
to Mch following dermal diisocyanate exposure, BALB/c mice received
nine dermal exposures over a period of 28 days to one of six isocyanates,
DNCB, or vehicle. Mice were then challenged with increasing doses
of Mch and responsiveness was assessed using whole-body plethysmography.
Serum antibody responses and cytokine mRNA profiles in the draining
lymph node were also assessed. In separate experiments, cytokine
protein assays were performed after five dermal exposures over a
14-day period. The response pattern for interleukin (IL)-4, IL-10,
and IL-13 for the different isocyanates was highly reproducible as
determined by RNAse protection assay, reverse transcription-PCR,
or cytokine protein levels. However, the relative differences in
T-helper cytokine profiles were not predictive of relative differences
in either total serum IgE or respiratory responses to Mch following
dermal exposure. The data suggest that the cytokine profiling approach
needs to be further developed and refined before adoption and that
other approaches to hazard identification should be pursued as well.
Based on the weight of evidence from all the assays performed, it
appears that all six isocyanates tested have some potential to cause
respiratory hypersensitivity following dermal exposure.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/94/1/108}
}
@ARTICLE{Sellam2009,
author = {Sellam, Adnane and Al-Niemi, Thamir and McInnerney, Kathleen and
Brumfield, Susan and Nantel, Andre and Suci, Peter},
title = {A Candida albicans early stage biofilm detachment event in rich medium},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {25},
number = {1},
abstract = {BACKGROUND:Dispersal from Candida albicans biofilms that colonize
catheters is implicated as a primary factor in the link between contaminated
catheters and life threatening blood stream infections (BSI). Appropriate
in vitro C. albicans biofilm models are needed to probe factors that
induce detachment events.RESULTS:Using a flow through system to culture
C. albicans biofilms we characterized a detachment process which
culminates in dissociation of an entire early stage biofilm from
a silicone elastomer surface. We analyzed the transcriptome response
at time points that bracketed an abrupt transition in which a strong
adhesive association with the surface is weakened in the initial
stages of the process, and also compared batch and biofilm cultures
at relevant time points. K means analysis of the time course array
data revealed categories of genes with similar patterns of expression
that were associated with adhesion, biofilm formation and glycoprotein
biosynthesis. Compared to batch cultures the biofilm showed a pattern
of expression of metabolic genes that was similar to the C. albicans
response to hypoxia. However, the loss of strong adhesion was not
obviously influenced by either the availability of oxygen in the
medium or at the silicone elastomer surface. The detachment phenotype
of mutant strains in which selected genes were either deleted or
overexpressed was characterized. The microarray data indicated that
changes associated with the detachment process were complex and,
consistent with this assessment, we were unable to demonstrate that
transcriptional regulation of any single gene was essential for loss
of the strong adhesive association.CONCLUSION:The massive dispersal
of the early stage biofilm from a biomaterial surface that we observed
is not orchestrated at the level of transcriptional regulation in
an obvious manner, or is only regulated at this level by a small
subpopulation of cells that mediate adhesion to the surface.},
doi = {10.1186/1471-2180-9-25},
issn = {1471-2180},
pubmedid = {19187560},
url = {http://www.biomedcentral.com/1471-2180/9/25}
}
@ARTICLE{Sellam2010,
author = {Sellam, Adnane and Askew, Christopher and Epp, Elias and Tebbji,
Faiza and Mullick, Alaka and Whiteway, Malcolm and Nantel, Andre},
title = {Role of Transcription Factor CaNdt80p in Cell Separation, Hyphal
Growth, and Virulence in Candida albicans},
journal = {Eukaryot. Cell},
year = {2010},
volume = {9},
pages = {634--644},
number = {4},
month = apr,
abstract = {The NDT80/PhoG transcription factor family includes ScNdt80p, a key
modulator of the progression of meiotic division in Saccharomyces
cerevisiae. In Candida albicans, a member of this family, CaNdt80p,
modulates azole sensitivity by controlling the expression of ergosterol
biosynthesis genes. We previously demonstrated that CaNdt80p promoter
targets, in addition to ERG genes, were significantly enriched in
genes related to hyphal growth. Here, we report that CaNdt80p is
indeed required for hyphal growth in response to different filament-inducing
cues and for the proper expression of genes characterizing the filamentous
transcriptional program. These include noteworthy genes encoding
cell wall components, such as HWP1, ECE1, RBT4, and ALS3. We also
show that CaNdt80p is essential for the completion of cell separation
through the direct transcriptional regulation of genes encoding the
chitinase Cht3p and the cell wall glucosidase Sun41p. Consistent
with their hyphal defect, ndt80 mutants are avirulent in a mouse
model of systemic candidiasis. Interestingly, based on functional-domain
organization, CaNdt80p seems to be a unique regulator characterizing
fungi from the CTG clade within the subphylum Saccharomycotina. Therefore,
this study revealed a new role of the novel member of the fungal
NDT80 transcription factor family as a regulator of cell separation,
hyphal growth, and virulence.},
url = {http://ec.asm.org/cgi/content/abstract/9/4/634}
}
@ARTICLE{Sellam2010a,
author = {Sellam, Adnane and Hogues, Hervé and Askew, Christopher and Tebbji,
Faiza and van het Hoog, Marco and Lavoie, Hugo and Kumamoto, Carol
and Whiteway, Malcolm and Nantel, André},
title = {Experimental annotation of the human pathogen Candida albicans coding
and noncoding transcribed regions using high-resolution tiling arrays},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R71},
number = {7},
abstract = {BACKGROUND:Compared to other model organisms and despite the clinical
relevance of the pathogenic yeast Candida albicans, no comprehensive
analysis has been done to provide experimental support of its in
silico-based genome annotation.RESULTS:We have undertaken a genome-wide
experimental annotation to accurately uncover the transcriptional
landscape of the pathogenic yeast C. albicans using strand-specific
high-density tiling arrays. RNAs were purified from cells growing
under conditions relevant to C. albicans pathogenicity, including
biofilm, lab-grown yeast and serum-induced hyphae, as well as cells
isolated from the mouse caecum. This work provides a genome-wide
experimental validation for a large number of predicted ORFs for
which transcription had not been detected by other approaches. Additionally,
we identified more than 2,000 novel transcriptional segments, including
new ORFs and exons, non-coding RNAs (ncRNAs) as well as convincing
cases of antisense gene transcription. We also characterized the
5' and 3' UTRs of expressed ORFs, and established that genes with
long 5' UTRs are significantly enriched in regulatory functions controlling
filamentous growth. Furthermore, we found that genomic regions adjacent
to telomeres harbor a cluster of expressed ncRNAs. To validate and
confirm new ncRNA candidates, we adapted an iterative strategy combining
both genome-wide occupancy of the different subunits of RNA polymerases
I, II and III and expression data. This comprehensive approach allowed
the identification of different families of ncRNAs.CONCLUSIONS:In
summary, we provide a comprehensive expression atlas that covers
relevant C. albicans pathogenic developmental stages in addition
to the discovery of new ORF and non-coding genetic elements.},
doi = {10.1186/gb-2010-11-7-r71},
issn = {1465-6906},
pubmedid = {20618945},
url = {http://genomebiology.com/2010/11/7/R71}
}
@ARTICLE{Sellam2009a,
author = {Sellam, Adnane and Tebbji, Faiza and Nantel, Andre},
title = {Role of Ndt80p in Sterol Metabolism Regulation and Azole Resistance
in Candida albicans},
journal = {Eukaryot. Cell},
year = {2009},
volume = {8},
pages = {1174--1183},
number = {8},
month = aug,
abstract = {The Ndt80p transcription factor modulates azole tolerance in Candida
albicans by controlling the expression of the gene for the drug efflux
pump Cdr1p. To date, the contribution of this transcriptional modulator
to drug tolerance is not yet well understood. Here, we investigate
the role of Ndt80p in mediating fluconazole tolerance by determining
its genome-wide occupancy using chromatin immunoprecipitation coupled
to high-density tiling arrays. Ndt80p was found to bind a large number
of gene promoters with diverse biological functions. Gene ontology
analysis of these Ndt80p targets revealed a significant enrichment
in gene products related to the cell wall, carbohydrate metabolism,
stress responses, hyphal development, multidrug transport, and the
cell cycle. Ndt80p was found on the promoters of ergosterol biosynthesis
genes, including on the azole target Erg11p. Additionally, expression
profiling was used to identify fluconazole-responsive genes that
require Ndt80p for their proper expression. We found that Ndt80p
is crucial for the expression of numerous fluconazole-responsive
genes, especially genes involved in ergosterol metabolism. Therefore,
by combining genome-wide location and transcriptional profiling,
we have characterized the Ndt80p fluconazole-dependent regulon and
demonstrated the key role of this global transcriptional regulator
in modulating sterol metabolism and drug resistance in C. albicans.},
url = {http://ec.asm.org/cgi/content/abstract/8/8/1174}
}
@ARTICLE{Sellamuthu2011,
author = {Sellamuthu, Rajendran and Umbright, Christina and Roberts, Jenny
R. and Chapman, Rebecca and Young, Shih-Houng and Richardson, Diana
and Leonard, Howard and McKinney, Walter and Chen, Bean and Frazer,
David and Li, Shengqiao and Kashon, Michael and Joseph, Pius},
title = {Blood Gene Expression Profiling Detects Silica Exposure and Toxicity},
journal = {Toxicol. Sci.},
year = {2011},
volume = {122},
pages = {253-264},
number = {2},
abstract = {Blood gene expression profiling was investigated as a minimally invasive
surrogate approach to detect silica exposure and resulting pulmonary
toxicity. Rats were exposed by inhalation to crystalline silica (15
mg/m3, 6 h/day, 5 days), and pulmonary damage and blood gene expression
profiles were determined after latency periods (0-16 weeks). Silica
exposure resulted in pulmonary toxicity as evidenced by histological
and biochemical changes in the lungs. The number of significantly
differentially expressed genes in the blood, identified by microarray
analysis, correlated with the severity of silica-induced pulmonary
toxicity. Functional analysis of the differentially expressed genes
identified activation of inflammatory response as the major biological
signal. Induction of pulmonary inflammation, as suggested by the
blood gene expression data, was supported by significant increases
in the number of macrophages and infiltrating neutrophils as well
as the activity of pro-inflammatory chemokines observed in the lungs
of the silica-exposed rats. A gene expression signature developed
using the blood gene expression data predicted the exposure of rats
to lower, minimally toxic and nontoxic concentrations of silica.
Taken together, our findings suggest the potential application of
peripheral blood gene expression profiling as a minimally invasive
surrogate approach to detect pulmonary toxicity induced by silica
in the rat. However, further research is required to determine the
potential application of our findings specifically to monitor human
exposure to silica and the resulting pulmonary effects.},
doi = {10.1093/toxsci/kfr125},
eprint = {http://toxsci.oxfordjournals.org/cgi/reprint/122/2/253.pdf},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/122/2/253}
}
@ARTICLE{Selley2007,
author = {Selley, Paula and Bruner, Jimmy and Kelly, Fiona and Maurio, Frank
and Waters, Michelle and Strum, Jay},
title = {Automated Solutions for Total RNA Isolation from Diverse Sample Types},
journal = {Clinics in Laboratory Medicine},
year = {2007},
volume = {27},
pages = {155--161},
number = {1},
month = mar,
abstract = {In response to the increasing demands to generate larger amounts of
quality data faster, specifically in the area of RNA isolation to
support gene expression assays, the authors have adopted several
automated solutions for isolating total RNA from a variety of sample
types, (eg, blood, cells, and tissue). By using automated solutions,
the authors were able to increase their throughput without compromising
data integrity.},
booktitle = {Laboratory Automation},
issn = {0272-2712},
url = {http://www.sciencedirect.com/science/article/B75HR-4NF4D3N-F/2/6e6aa8ece9713576e8a8d390586c5380}
}
@ARTICLE{SellinJeffries2011,
author = {Sellin Jeffries, Marlo K. and Mehinto, Alvine C. and Carter, Barbara
and Denslow, Nancy D. and Kolok, Alan S.},
title = {Taking microarrays to the field: Differential hepatic gene expression
of caged fathead minnows from Nebraska watersheds},
journal = {Environmental Science \& Technology},
year = {2011},
volume = {0},
pages = {null},
number = {ja},
abstract = { This study aimed to evaluate the utility of microarrays as a biomonitoring
tool in field studies. A 15,000-oligonucleotide microarray was used
to measure the hepatic gene expression of fathead minnows (Pimephales
promelas) caged in four Nebraska, USA watersheds - the Niobrara and
Dismal Rivers (low-impact agricultural sites) and the Platte and
Elkhorn Rivers (high-impact agricultural sites). Gene expression
profiles were site specific and fish from the low- and high-impact
sites aggregated into distinct groups. Over 1500 genes were differentially
regulated between fish from the low- and high-impact sites. Many
gene expression differences (1218) were also noted when the Platte
and Elkhorn minnows were compared to one another and Platte fish
experienced a higher degree of transcript alterations than Elkhorn
fish. These findings indicate that there are differences between
the low-impact and high-impact sites, as well as between the two
high-impact sites. Historical water quality data supports these results
as only trace levels of agrichemicals have been detected at the low-impact
sites, while substantial levels of agrichemicals have been reported
at the high-impact sites with agrichemical loads at the Platte generally
exceeding those at the Elkhorn. Overall, this study demonstrates
that microarrays can be utilized to discriminate sites with different
contaminant loads from one another. },
doi = {10.1021/es2039097},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/es2039097},
url = {http://pubs.acs.org/doi/abs/10.1021/es2039097}
}
@ARTICLE{Sellman2008,
author = {Sellman, Bret R. and Timofeyeva, Yekaterina and Nanra, Jasdeep and
Scott, Adrienne and Fulginiti, James P. and Matsuka, Yury V. and
Baker, Steve M.},
title = {Expression of Staphylococcus epidermidis SdrG Increases following
Exposure to an In Vivo Environment},
journal = {Infect. Immun.},
year = {2008},
volume = {76},
pages = {2950--2957},
number = {7},
month = jul,
abstract = {SdrG is a surface-associated fibrinogen binding protein present in
most strains of Staphylococcus epidermidis. Surface expression of
SdrG was not detected by flow cytometry or immunofluorescence microscopy
on S. epidermidis 0-47 grown in nutrient broth or in the presence
of human serum. sdrG transcript levels increased 1 hour following
a shift from growth in nutrient broth to growth in the bloodstream
of a mouse and resulted in a concomitant increase in protein levels
as detected by immunofluorescence microscopy. The environmental signal(s)
resulting in the increase in expression is elusive, as growth under
conditions known to mimic in vivo conditions (elevated CO2, iron
limitation, human serum, and citrated human blood) did not affect
expression of SdrG. Immunizing mice with either the N1N2N3 (amino
acids 50 to 597) or N2N3 (amino acids 273 to 597) subdomain of the
N-terminal A domain of recombinant SdrG (rSdrG) elicited a robust
antibody response; however, only mice vaccinated with rSdrGN23 exhibited
a significant reduction in 0-47 recovered after experimental infection.
Since SdrG is expressed early during infection in response to specific
host environmental cues present in the bloodstream and since antibodies
to it are effective in reducing bacteremia, SdrG possesses attributes
of a vaccine component effective against the pathogenic form of the
ubiquitous human commensal S. epidermidis.},
url = {http://iai.asm.org/cgi/content/abstract/76/7/2950}
}
@ARTICLE{Selman2006,
author = {Selman, Colin and Kerrison, Nicola D. and Cooray, Anisha and Piper,
Matthew D. W. and Lingard, Steven J. and Barton, Richard H. and Schuster,
Eugene F. and Blanc, Eric and Gems, David and Nicholson, Jeremy K.
and Thornton, Janet M. and Partridge, Linda and Withers, Dominic
J.},
title = {Coordinated multitissue transcriptional and plasma metabonomic profiles
following acute caloric restriction in mice},
journal = {Physiol Genomics},
year = {2006},
volume = {27},
pages = {187--200},
number = {3},
month = nov,
abstract = {Caloric restriction (CR) increases healthy life span in a range of
organisms. The underlying mechanisms are not understood but appear
to include changes in gene expression, protein function, and metabolism.
Recent studies demonstrate that acute CR alters mortality rates within
days in flies. Multitissue transcriptional changes and concomitant
metabolic responses to acute CR have not been described. We generated
whole genome RNA transcript profiles in liver, skeletal muscle, colon,
and hypothalamus and simultaneously measured plasma metabolites using
proton nuclear magnetic resonance in mice subjected to acute CR.
Liver and muscle showed increased gene expressions associated with
fatty acid metabolism and a reduction in those involved in hepatic
lipid biosynthesis. Glucogenic amino acids increased in plasma, and
gene expression for hepatic gluconeogenesis was enhanced. Increased
expression of genes for hormone-mediated signaling and decreased
expression of genes involved in protein binding and development occurred
in hypothalamus. Cell proliferation genes were decreased and cellular
transport genes increased in colon. Acute CR captured many, but not
all, hepatic transcriptional changes of long-term CR. Our findings
demonstrate a clear transcriptional response across multiple tissues
during acute CR, with congruent plasma metabolite changes. Liver
and muscle switched gene expression away from energetically expensive
biosynthetic processes toward energy conservation and utilization
processes, including fatty acid metabolism and gluconeogenesis. Both
muscle and colon switched gene expression away from cellular proliferation.
Mice undergoing acute CR rapidly adopt many transcriptional and metabolic
changes of long-term CR, suggesting that the beneficial effects of
CR may require only a short-term reduction in caloric intake.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/27/3/187}
}
@ARTICLE{Selman2008,
author = {Selman, Colin and Lingard, Steven and Choudhury, Agharul I. and Batterham,
Rachel L. and Claret, Marc and Clements, Melanie and Ramadani, Faruk
and Okkenhaug, Klaus and Schuster, Eugene and Blanc, Eric and Piper,
Matthew D. and Al-Qassab, Hind and Speakman, John R. and Carmignac,
Danielle and Robinson, Iain C. A. and Thornton, Janet M. and Gems,
David and Partridge, Linda and Withers, Dominic J.},
title = {Evidence for lifespan extension and delayed age-related biomarkers
in insulin receptor substrate 1 null mice},
journal = {FASEB J},
year = {2008},
volume = {22},
pages = {807--818},
number = {3},
month = mar,
abstract = {Recent evidence suggests that alterations in insulin/insulin-like
growth factor 1 (IGF1) signaling (IIS) can increase mammalian life
span. For example, in several mouse mutants, impairment of the growth
hormone (GH)/IGF1 axis increases life span and also insulin sensitivity.
However, the intracellular signaling route to altered mammalian aging
remains unclear. We therefore measured the life span of mice lacking
either insulin receptor substrate (IRS) 1 or 2, the major intracellular
effectors of the IIS receptors. Our provisional results indicate
that female Irs1-/- mice are long-lived. Furthermore, they displayed
resistance to a range of age-sensitive markers of aging including
skin, bone, immune, and motor dysfunction. These improvements in
health were seen despite mild, lifelong insulin resistance. Thus,
enhanced insulin sensitivity is not a prerequisite for IIS mutant
longevity. Irs1-/- female mice also displayed normal anterior pituitary
function, distinguishing them from long-lived somatotrophic axis
mutants. In contrast, Irs2-/- mice were short-lived, whereas Irs1+/-
and Irs2+/- mice of both sexes showed normal life spans. Our results
therefore suggest that IRS1 signaling is an evolutionarily conserved
pathway regulating mammalian life span and may be a point of intervention
for therapies with the potential to delay age-related processes.--Selman,
C., Lingard, S., Choudhury, A. I., Batterham, A. L., Claret, M.,
Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E.,
Piper, M. D., Al-Qassab, H., Speakman, J. R., Carmignac, D., Robinson,
I. C. A., Thornton, J. M., Gems, D., Partridge, L., Withers, D. J.
Evidence for lifespan extension and delayed age-related biomarkers
in insulin receptor substrate 1 null mice.},
url = {http://www.fasebj.org/cgi/content/abstract/22/3/807}
}
@ARTICLE{Selvarajah2007,
author = {Selvarajah, Shamini and Yoshimoto, Maisa and Maire, Georges and Paderova,
Jana and Bayani, Jane and Squire, Jeremy A. and Zielenska, Maria},
title = {Identification of cryptic microaberrations in osteosarcoma by high-definition
oligonucleotide array comparative genomic hybridization},
journal = {Cancer Genetics and Cytogenetics},
year = {2007},
volume = {179},
pages = {52--61},
number = {1},
month = nov,
abstract = {Osteosarcoma (OS) is an aggressive bone tumor characterized by complex
abnormal karyotypes and a high level of genomic instability. Using
high-resolution array comparative genomic hybridization (aCGH), a
novel class of localized copy number variations called microaberrations
has been detected. These genomic anomalies typically involve DNA
imbalances affecting 700 kb to 1 Mb DNA, and are often associated
with some type of genetic syndromes. Because the origin of instability
in OS is poorly understood, we used aCGH to determine whether microaberrations
were a characteristic of four OS cell lines: U-2 OS, HOS, MG-63,
and SAOS-2. TP53 is mutated in SAOS-2, a line in which 17 microaberrations
were found. In contrast, U-2 OS, which has a wild-type TP53, had
only six such anomalies, the lowest incidence. A 500-kb microaberration
within a region of gain at 5p15.33 in SAOS-2 was confirmed by fluorescence
in situ hybridization. Significantly, this genomic location is close
to the TERT gene, a region of gain in all four cell lines. To our
knowledge, this is the first systematic analysis of the incidence
of microaberrations in OS. The high levels of these anomalies detected
suggest that the instability processes in OS that lead to a highly
abnormal karyotypes may also be associated with acquisition of genomic
microaberrations.},
issn = {0165-4608},
url = {http://www.sciencedirect.com/science/article/B6T53-4R1WNX9-B/2/c3ba3ba998c0da29d7c3f6796d0db602}
}
@ARTICLE{Selvaraju2011,
author = {Selvaraju, Suresh B. and Gripka, Megan and Estes, Kristen and Nguyen,
Ashley and Jackson, Mary Anne and Selvarangan, Rangaraj},
title = {Detection of toxigenic Clostridium difficile in pediatric stool samples:
an evaluation of Quik Check Complete Antigen assay, BD GeneOhm Cdiff
PCR, and ProGastro Cd PCR assays},
journal = {Diagn Microbiol Infect Dis},
year = {2011},
volume = {71},
pages = {224--229},
number = {3},
month = nov,
abstract = {The performance of C. Diff Quik Chek Complete (QCC), BD GeneOhm Cdiff
PCR (BD), and ProGastro Cd PCR (PG) assays was evaluated in detecting
Clostridium difficile infection (CDI) in children using 200 frozen
stool specimens. The results of the tests were compared to the toxigenic
culture (TC) as ‘gold standard.’ The sensitivity, specificity,
positive predictive value, and negative predictive value were as
follows. QCC antigen (GDH + Toxin-A/B) = 70.8%, 97.4%, 89.5%, and
91.4%; BD PCR = 89.6%, 96.7%, 89.6%, and 96.7%; PG PCR = 100%, 93.4%,
82.8%, and 100%. Polymerase chain reaction (PCR) assays detected
an additional 11 positives missed by TC, 7 of which were confirmed
positive by an alternate tcdB gene PCR assay. However, retrospective
clinical chart review indicated CDI in only 3 of the 11 patients
in whom C. difficile was detected by PCR only. A 2-step algorithm
utilizing QCC antigen test as a screening test followed by confirmation
of GDH-positive and toxin-negative samples with either BD or PG PCR
assay will provide rapid and accurate results for majority of the
samples and reduce laboratory testing cost.},
issn = {0732-8893},
keywords = {Clostridium difficile, C Diff Quik Check Complete, ProGastro PCR,
BD GeneOhm PCR},
publisher = {Elsevier Biomedical,},
refid = {S0732-8893(11)00310-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0732889311003105?showall=true}
}
@BOOK{Semizarov2008,
title = {Genomics Technologies as Tools in Drug Discovery},
publisher = {John Wiley \& Sons, Inc.},
year = {2008},
author = {Semizarov, Dimitri and Blomme, Eric},
pages = {25--103},
abstract = {Summary 10.1002/9780470409770.ch2.abs This chapter contains sections
titled:},
booktitle = {Genomics in Drug Discovery and Development},
issn = {9780470409770},
keywords = {genomic technologies and methodologies, gene expression microarray
methodologies, gene set enrichment analysis (GSEA)},
url = {http://dx.doi.org/10.1002/9780470409770.ch2}
}
@ARTICLE{Semizarov2004,
author = {Semizarov, Dimitri and Kroeger, Paul and Fesik, Stephen},
title = {siRNA-mediated gene silencing: a global genome view},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {3836--3845},
number = {13},
month = jul,
abstract = {The task of specific gene knockdown in vitro has been facilitated
through the use of short interfering RNA (siRNA), which is now widely
used for studying gene function, as well as for identifying and validating
new drug targets. We explored the possibility of using siRNA for
dissecting cellular pathways by siRNA-mediated gene silencing followed
by gene expression profiling and systematic pathway analysis. We
used siRNA to eliminate the Rb1 gene in human cells and determined
the effects of Rb1 knockdown on the cell by using microarray-based
gene expression profiling coupled with quantitative pathway analysis
using the GenMapp and MappFinder software. Retinoblastoma protein
is one of the key cell cycle regulators, which exerts its function
through its interactions with E2F transcription factors. Rb1 knockdown
affected G1/S and G2/M transitions of the cell cycle, DNA replication
and repair, mitosis, and apoptosis, indicating that siRNA-mediated
transient elimination of Rb1 mimics the control of cell cycle through
Rb1 dissociation from E2F. Additionally, we observed significant
effects on the processes of DNA damage response and epigenetic regulation
of gene expression. Analysis of transcription factor binding sites
was utilized to distinguish between putative direct targets and genes
induced through other mechanisms. Our approach, which combines the
use of siRNA-mediated gene silencing, mediated microarray screening
and quantitative pathway analysis, can be used in functional genomics
to elucidate the role of the target gene in intracellular pathways.
The approach also holds significant promise for compound selection
in drug discovery.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/13/3836}
}
@ARTICLE{Sen2011,
author = {Sen, Anindya and Yokokura, Takakazu and Kankel, Mark W. and Dimlich,
Douglas N. and Manent, Jan and Sanyal, Subhabrata and Artavanis-Tsakonas,
Spyros},
title = {Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling},
journal = {J. Cell Biol.},
year = {2011},
volume = {192},
pages = {481--495},
number = {3},
month = feb,
abstract = {Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder
characterized by motor neuron loss and muscle atrophy, has been linked
to mutations in the Survival Motor Neuron (SMN) gene. Based on an
SMA model we developed in Drosophila, which displays features that
are analogous to the human pathology and vertebrate SMA models, we
functionally linked the fibroblast growth factor (FGF) signaling
pathway to the Drosophila homologue of SMN, Smn. Here, we characterize
this relationship and demonstrate that Smn activity regulates the
expression of FGF signaling components and thus FGF signaling. Furthermore,
we show that alterations in FGF signaling activity are able to modify
the neuromuscular junction defects caused by loss of Smn function
and that muscle-specific activation of FGF is sufficient to rescue
Smn-associated abnormalities.},
comment = {10.1083/jcb.201004016},
url = {http://jcb.rupress.org/cgi/content/abstract/192/3/481}
}
@ARTICLE{Sen2005,
author = {Sen, Banalata and Wang, Amy and Hester, Susan D. and Robertson, John
L. and Wolf, Douglas C.},
title = {Gene expression profiling of responses to dimethylarsinic acid in
female F344 rat urothelium},
journal = {Toxicology},
year = {2005},
volume = {215},
pages = {214--226},
number = {3},
month = nov,
abstract = {Gene expression profiling has been shown to be useful for identifying
underlying mechanisms of toxicity, determining patterns of biological
response, and elucidating candidate markers of exposure and response.
Inorganic arsenic (iAs) is a human carcinogen and epidemiologic evidence
implicates it in the development of urinary bladder cancer. Dimethylarsinic
acid (DMA), the major excreted metabolite of iAs in humans, is a
known rat bladder carcinogen. To examine the changes associated with
DMA exposure, microarray analysis of the urothelium was performed
in female F344 rats exposed to non-toxic and toxic doses of DMA in
their drinking water for 28 days. A novel method for isolating predominantly
urothelial cells was developed. Gene expression profiling of the
urothelium using a custom 2-dye spotted array revealed that DMA treatment
modulated the expression of transcripts of genes that regulate apoptosis,
cell cycle regulation and the oxidative stress response. Expression
of genes mapping to pathways involved in cancer control processes
were also altered after DMA exposure. Morphological data suggested
a dose dependent increase in cellular toxicity. Significant changes
in differential gene expression were present after all treatments
event at doses where standard toxicological responses were not detectable.
The greatest perturbation in gene expression was present in rats
after treatment with 40 ppm DMA. Doses which produced no histologic
or ultrastructural evidence of toxicity (non-toxic) could be differentiated
from toxic doses based on the expression of a subset of genes, which
control cell signaling and the stress response. These reported changes
in gene expression show similarities between the mechanisms of action
of DMA in vivo and those previously described for iAs in vitro. These
data illustrate the utility of transcriptional profiling and its
potential in predicting key mechanistic pathways involved in toxicity
and as a time efficient tool to inform the mode of action analysis
in risk assessment.},
issn = {0300-483X},
keywords = {Dimethylarsinic acid, Arsenic, Urothelium, Urinary bladder, Gene expression,
Microarray},
url = {http://www.sciencedirect.com/science/article/B6TCN-4GY87B1-2/2/b464e536f9c0c703f54e81ea4cdd560d}
}
@ARTICLE{Sen2004,
author = {Sen, Banalata and Wolf, Douglas C. and Hester, Susan D.},
title = {The transcriptional profile of the kidney in Tsc2 heterozygous mutant
Long Evans (Eker) rats compared to wild-type},
journal = {Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis},
year = {2004},
volume = {549},
pages = {213--224},
number = {1-2},
month = may,
abstract = {Hereditary renal cell carcinoma (RCC) in Eker rats results from an
inherited insertional mutation in the Tsc2 tumor suppressor gene
and provides a valuable experimental model to characterize the function
of the Tsc2 gene product, tuberin in vivo. The Tsc2 mutation predisposes
the Eker rat to develop renal tumors at an early age. The exact mechanism
of Tsc2 mediated tumor suppression is not known, however, there is
evidence that it is most likely mediated by changes in cell cycle
regulation via the PI3K/Akt pathway. The present study was designed
to identify if gene expression was different in Tsc2 heterozygous
mutant rat kidney compared to wild-type and if any of those differences
are associated with tumorigenesis. cDNA microarray analysis of the
untreated Tsc2 (+/-) mutant Long Evans (Eker) rat was compared to
the Tsc2 (+/+) wild-type Long Evans rat to search for patterns that
might be indicative of the intrinsic role of Tsc2. Of 4395 genes
queried, 3.2% were significantly altered in kidneys from heterozygous
mutant rats, of which 110 (76%) were up-regulated and 34 (24%) were
down-regulated relative to the wild-type. The genes with altered
expression belonged to the functional categories of cell cycle regulation,
cell proliferation, cell adhesion and endocytosis. Many of these
genes appear to be directly or indirectly regulated by the PI3K/Akt
pathway. In addition to the PI3K/Akt pathway, other signaling pathways
were also differentially expressed in Tsc2 mutant Eker rat kidneys
compared to wild-type rats. The gene expression profiles of the Tsc2
heterozygous mutant and wild-type animals highlights new pathways
for investigation that may be associated with the tumorigenic activity
of tuberin loss and correlate with the enhanced susceptibility of
the Tsc2 mutant animal's tendency to develop renal cell carcinoma.},
booktitle = {Toxicogenomics},
issn = {0027-5107},
keywords = {Tsc2 gene, Mutation, Kidney, Eker rat, Gene expression, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T2C-4C5HW7M-1/2/e6e7b1ad2324e41a1069d0d1adfd5d5b}
}
@ARTICLE{Senanayake2007,
author = {Senanayake, Saranga and Brownrigg, Leon M. and Panicker, Vijay and
Croft, Kevin D. and Joyce, David A. and Steer, James H. and Puddey,
Ian B. and Yeap, Bu B.},
title = {Monocyte-derived macrophages from men and women with Type 2 diabetes
mellitus differ in fatty acid composition compared with non-diabetic
controls},
journal = {Diabetes Research and Clinical Practice},
year = {2007},
volume = {75},
pages = {292--300},
number = {3},
month = mar,
issn = {0168-8227},
keywords = {Type 2 diabetes, Macrophages, Gene expression, Fatty acids},
url = {http://www.sciencedirect.com/science/article/B6T5Y-4KTMTNX-2/2/dc6b31570cc723f7a53e65cc2ef02131}
}
@ARTICLE{SenBanerjee2004,
author = {SenBanerjee, Sucharita and Lin, Zhiyong and Atkins, G. Brandon and
Greif, Daniel M. and Rao, Ravi M. and Kumar, Ajay and Feinberg, Mark
W. and Chen, Zhiping and Simon, Daniel I. and Luscinskas, F. William
and Michel, Thomas M. and Gimbrone, Michael A., Jr. and Garcia-Cardena,
Guillermo and Jain, Mukesh K.},
title = {KLF2 Is a Novel Transcriptional Regulator of Endothelial Proinflammatory
Activation},
journal = {J. Exp. Med.},
year = {2004},
volume = {199},
pages = {1305--1315},
number = {10},
month = may,
abstract = {The vascular endothelium is a critical regulator of vascular function.
Diverse stimuli such as proinflammatory cytokines and hemodynamic
forces modulate endothelial phenotype and thereby impact on the development
of vascular disease states. Therefore, identification of the regulatory
factors that mediate the effects of these stimuli on endothelial
function is of considerable interest. Transcriptional profiling studies
identified the Kruppel-like factor (KLF)2 as being inhibited by the
inflammatory cytokine interleukin-1{beta} and induced by laminar
shear stress in cultured human umbilical vein endothelial cells.
Overexpression of KLF2 in umbilical vein endothelial cells robustly
induced endothelial nitric oxide synthase expression and total enzymatic
activity. In addition, KLF2 overexpression potently inhibited the
induction of vascular cell adhesion molecule-1 and endothelial adhesion
molecule E-selectin in response to various proinflammatory cytokines.
Consistent with these observations, in vitro flow assays demonstrate
that T cell attachment and rolling are markedly attenuated in endothelial
monolayers transduced with KLF2. Finally, our studies implicate recruitment
by KLF2 of the transcriptional coactivator cyclic AMP response element-binding
protein (CBP/p300) as a unifying mechanism for these various effects.
These data implicate KLF2 as a novel regulator of endothelial activation
in response to proinflammatory stimuli.},
url = {http://jem.rupress.org/cgi/content/abstract/199/10/1305}
}
@ARTICLE{Senda2004,
author = {Senda, Kaori and Ogawa, Ken'ichi},
title = {Induction of PR-1 Accumulation Accompanied by Runaway Cell Death
in the lsd1 Mutant of Arabidopsis is Dependent on Glutathione Levels
but Independent of the Redox State of Glutathione},
journal = {Plant Cell Physiol.},
year = {2004},
volume = {45},
pages = {1578--1585},
number = {11},
month = nov,
abstract = {The lesions simulating disease (lsd) mutants of Arabidopsis spontaneously
develop hypersensitive-response-like lesions in the absence of pathogens.
To address the function of the redox regulator glutathione in disease
resistance, we examined the relationship between endogenous glutathione
and PR-1 accumulation using one of these mutants, lsd1, as a disease
resistance model. Lesion formation on lsd1 was suppressed by weak
light and initiated by the subsequent transition to normal light.
The application of buthionine sulfoximine, a specific inhibitor of
glutathione biosynthesis, suppressed conditionally induced runaway
cell death and expression of the PR-1 gene, suggesting that glutathione
regulates the conditional cell death and PR-1 gene expression. The
application of reduced (GSH) or oxidized (GSSG) glutathione to lsd1
upregulated the level of total glutathione ([GSH]+[GSSG]) accompanied
by hastened accumulation of PR-1, and the basal level of total glutathione
in lsd1 was higher than that in wild-type plants. The glutathione
redox state defined as [GSH]/([GSH]+[GSSG]) decreased following the
conditional transition, but the suppression of this decrease by the
application of GSH did not inhibit the accumulation of PR-1. Taken
together, conditional PR-1 accumulation in lsd1 is regulated not
by the redox state but by the endogenous level of glutathione.},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/45/11/1578}
}
@ARTICLE{Sengupta2007,
author = {Sengupta, Anamika and Baker, Tabari and Chakrabarti, Nilkanta and
Whittaker, Joseph A. and Sridaran, Rajagopala},
title = {Localization of Immunoreactive Gonadotropin-releasing Hormone and
Relative Expression of Its mRNA in the Oviduct During Pregnancy in
Rats},
journal = {J. Histochem. Cytochem.},
year = {2007},
volume = {55},
pages = {525--534},
number = {5},
month = may,
abstract = {This study was designed to determine the cellular and ultrastructural
distribution of the gonadotropin-releasing hormone (GnRH) and the
relative expression of its mRNA in the oviduct of rats during different
time points (days 7, 9, 16, and 20) of pregnancy. Immunofluorescent
localization and confocal microscopic techniques were used to determine
the cellular distribution of GnRH in the oviduct. Immunogold electron
microscopy indicated its localization at the ultrastructural level,
and real-time PCR was used to study the expression pattern of GnRH
mRNA in the oviduct during pregnancy. In general, GnRH was localized
within the epithelial cells lining the oviductal lumen at each selected
time point. A strong correlation between the fluorescence intensity
of GnRH-immunoreactive cells and the relative expression of GnRH
mRNA was noted on days 7 and 16, followed by a plateau by day 20.
At the ultrastructural level, uniform labeling of colloidal gold
particles was observed in secretory vesicles and lamella of the luminal
epithelium as well as the lumen of the oviduct. Collectively, these
results demonstrate for the first time that the oviductal epithelium
synthesizes and secretes the decapeptide GnRH during pregnancy in
rats, which may have a possible role in postimplantation embryonic
development and the maintenance of pregnancy. (J Histochem Cytochem
55:525-534, 2007)},
url = {http://www.jhc.org/cgi/content/abstract/55/5/525}
}
@ARTICLE{Sengupta2008,
author = {Sengupta, Anamika and Sridaran, Rajagopala},
title = {Expression and Localization of Gonadotropin-releasing Hormone Receptor
in the Rat Oviduct During Pregnancy},
journal = {J. Histochem. Cytochem.},
year = {2008},
volume = {56},
pages = {25--31},
number = {1},
month = jan,
abstract = {A recent study from our laboratory has shown cellular and ultrastructural
distribution of the gonadotropin-releasing hormone (GnRH) and the
relative expression of its mRNA in the rat oviduct during the postimplantation
period of pregnancy (days 7, 9, 16, and 20). To determine the possible
autocrine/paracrine involvement of the oviductal GnRH during pregnancy
in rats, the present investigation aims at the study of the relative
expression of GnRH receptor (GnRHR) mRNA by real-time PCR followed
by immunolocalization of the peptide in the oviduct during pregnancy.
Semiquantitative analysis of the oviductal GnRHR expression by Western
blot was done by densitometry of the signal intensity. Our results
indicate the expression of GnRHR mRNA in the rat oviduct throughout
the postimplantation period of pregnancy with no significant difference
in expression between the selected time points. Immunoreactive GnRHR
peptide was localized predominantly in the cytoplasm of the luminal
epithelial cells, with less expression in the cytoplasm of the stromal
cells and the smooth muscles throughout the oviduct. Signal intensity
of GnRHR was significantly lower during day 16 when compared to days
7 and 20. These results, for the first time, support the transcription
of GnRHR mRNA and its translation to protein in the rat oviduct throughout
the postimplantation period of pregnancy. The lower protein content
of GnRHR by day 16 may be indicative of ligand-induced downregulation
of the receptor expression. The present investigation thus strengthens
our previously postulated hypothesis regarding the receptor-mediated
autocrine/paracrine role of oviductal GnRH during pregnancy in rats.
(J Histochem Cytochem 56:25-31, 2008)},
url = {http://www.jhc.org/cgi/content/abstract/56/1/25}
}
@ARTICLE{Senju2009,
author = {Senju, Satoru and Haruta, Miwa and Matsunaga, Yusuke and Fukushima,
Satoshi and Ikeda, Tokunori and Takahashi, Kazutoshi and Okita, Keisuke
and Yamanaka, Shinya and Nishimura, Yasuharu},
title = {Characterization of Dendritic Cells and Macrophages Generated by
Directed Differentiation from Mouse Induced Pluripotent Stem Cells},
journal = {STEM CELLS},
year = {2009},
volume = {27},
pages = {1021--1031},
number = {5},
abstract = {Abstract 10.1002/stem.33.abs Methods have been established to generate
dendritic cells (DCs) from mouse and human embryonic stem (ES) cells.
We designated them as ES-DCs and mouse models have demonstrated the
induction of anti-cancer immunity and prevention of autoimmune disease
by in vivo administration of genetically engineered ES-DCs. For the
future clinical application of ES-DCs, the histoincompatibility between
patients to be treated and available human ES cells and the ethical
concerns associated with human ES cells may be serious obstacles.
However, recently developed induced pluripotent stem (iPS) cell technology
is expected to resolve these issues. This report describes the generation
and characterization of DCs derived from mouse iPS cells. The iPS
cell-derived DCs (iPS-DCs) possessed the characteristics of DCs including
the capacity of T-cell-stimulation, antigen-processing and presentation
and cytokine production. DNA microarray analyses revealed the upregulation
of genes related to antigen-presenting functions during differentiation
into iPS-DCs and similarity in gene expression profile in iPS-DCs
and bone marrow cell-derived DCs. Genetically modified iPS-DCs expressing
antigenic protein primed T-cells specific to the antigen in vivo
and elicited efficient antigen-specific anti-tumor immunity. In addition,
macrophages were generated from iPS cells (iPS-MP). iPS-MP were comparable
with bone marrow cell-derived macrophages in the cell surface phenotype,
functions, and gene expression profiles. Stem Cells 2009;27:1021–1031},
issn = {1549-4918},
keywords = {Induced pluripotent stem cells, Dendritic cells, Macrophages, MHC,
Embryonic stem cells, Cell therapy},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/stem.33}
}
@ARTICLE{Senocak2007,
author = {Senocak, Fatih S. and Si, Yaguang and Moya, Colby and Russell, William
K. and Russell, David H. and Lee, Kyongbum and Jayaraman, Arul},
title = {Effect of uncoupling protein-1 expression on 3T3-L1 adipocyte gene
expression},
journal = {FEBS Letters},
year = {2007},
volume = {581},
pages = {5865--5871},
number = {30},
month = dec,
abstract = {The mitochondrial respiratory uncoupling protein 1 (UCP1) partially
uncouples substrate oxidation and oxidative phosphorylation to promote
the dissipation of cellular biochemical energy as heat in brown adipose
tissue. We have recently shown that expression of UCP1 in 3T3-L1
white adipocytes reduces the accumulation of triglycerides. Here,
we investigated the molecular basis underlying UCP1 expression in
3T3-L1 adipocytes. Gene expression data showed that forced UCP1 expression
down-regulated several energy metabolism pathways; but ATP levels
were constant. A metabolic flux analysis model was used to reflect
the gene expression changes onto metabolic processes and concordance
was observed in the down-regulation of energy consuming pathways.
Our data suggest that adipocytes respond to long-term mitochondrial
uncoupling by minimizing ATP utilization.},
issn = {0014-5793},
keywords = {Uncoupling protein 1, Energy metabolism, Adipocytes},
url = {http://www.sciencedirect.com/science/article/B6T36-4R8KP8N-3/2/c8ef716ac8f1f03d8a5fc3d67bd05ae7}
}
@ARTICLE{SenthamaraiKannan2011,
author = {SenthamaraiKannan, Paranthaman and Sartor, Maureen A. and O'Connor,
Kyle T. and Neumann, Jonathan C. and Klyza, James P., Jr. and Succop,
Paul A. and Wagner, Brad D. and Karyala, Saikumar and Medvedovic,
Mario and Menon, Anil G.},
title = {Identification of maternally regulated fetal gene networks in the
placenta with a novel embryo transfer system in mice},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {317--324},
number = {7},
month = apr,
abstract = {The mechanisms for provisioning maternal resources to offspring in
placental mammals involve complex interactions between maternally
regulated and fetally regulated gene networks in the placenta, a
tissue that is derived from the zygote and therefore of fetal origin.
Here we describe a novel use of an embryo transfer system in mice
to identify gene networks in the placenta that are regulated by the
mother. Mouse embryos from the same strain of inbred mice were transferred
into a surrogate mother either of the same strain or from a different
strain, allowing maternal and fetal effects on the placenta to be
separated. After correction for sex and litter size, maternal strain
overrode fetal strain as the key determinant of fetal weight (P <
0.0001). Computational filtering of the placental transcriptome revealed
a group of 81 genes whose expression was solely dependent on the
maternal strain [P < 0.05, false discovery rate (FDR) < 0.10]. Network
analysis of this group of genes yielded highest statistical significance
for pathways involved in the regulation of cell growth (such as insulin-like
growth factors) as well as those involved in regulating lipid metabolism
[such as the low-density lipoprotein receptor-related protein 1 (LRP1),
LDL, and HDL], both of which are known to play a role in fetal development.
This novel technique may be generally applied to identify regulatory
networks involved in maternal-fetal interaction and eventually help
identify molecular targets in disorders of fetal growth.},
comment = {10.1152/physiolgenomics.00078.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/7/317}
}
@ARTICLE{Senti2008,
author = {Senti, Gabriele and Swoboda, Peter},
title = {Distinct Isoforms of the RFX Transcription Factor DAF-19 Regulate
Ciliogenesis and Maintenance of Synaptic Activity},
journal = {Mol. Biol. Cell},
year = {2008},
volume = {19},
pages = {5517--5528},
number = {12},
month = dec,
abstract = {Neurons form elaborate subcellular structures such as dendrites, axons,
cilia, and synapses to receive signals from their environment and
to transmit them to the respective target cells. In the worm Caenorhabditis
elegans, lack of the RFX transcription factor DAF-19 leads to the
absence of cilia normally found on 60 sensory neurons. We now describe
and functionally characterize three different isoforms of DAF-19.
The short isoform DAF-19C is specifically expressed in ciliated sensory
neurons and sufficient to rescue all cilia-related phenotypes of
daf-19 mutants. In contrast, the long isoforms DAF-19A/B function
in basically all nonciliated neurons. We discovered behavioral and
cellular phenotypes in daf-19 mutants that depend on the isoforms
daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent
of synaptic decline seen in many human neurodegenerative disorders.
The C. elegans daf-19 mutant worms can thus serve as a molecular
model for the mechanisms of functional neuronal decline.},
url = {http://www.molbiolcell.org/cgi/content/abstract/19/12/5517}
}
@ARTICLE{Seo2004,
author = {Seo, David and Wang, Tao and Dressman, Holly and Herderick, Edward
E. and Iversen, Edwin S. and Dong, Chunming and Vata, Korkut and
Milano, Carmelo A. and Rigat, Fabio and Pittman, Jennifer and Nevins,
Joseph R. and West, Mike and Goldschmidt-Clermont, Pascal J.},
title = {Gene Expression Phenotypes of Atherosclerosis},
journal = {Arterioscler Thromb Vasc Biol},
year = {2004},
volume = {24},
pages = {1922--1927},
number = {10},
month = oct,
abstract = {Objective-- Fulfilling the promise of personalized medicine by developing
individualized diagnostic and therapeutic strategies for atherosclerosis
will depend on a detailed understanding of the genes and gene variants
that contribute to disease susceptibility and progression. To that
end, our group has developed a nonbiased approach congruent with
the multigenic concept of complex diseases by identifying gene expression
patterns highly associated with disease states in human target tissues.
Methods and Results-- We have analyzed a collection of human aorta
samples with varying degrees of atherosclerosis to identify gene
expression patterns that predict a disease state or potential susceptibility.
We find gene expression signatures that relate to each of these disease
measures and are reliable and robust in predicting the classification
for new samples with >93% in each analysis. The genes that provide
the predictive power include many previously suspected to play a
role in atherosclerosis and additional genes without prior association
with atherosclerosis. Conclusion-- Hence, we are reporting a novel
method for generating a molecular phenotype of disease and then identifying
genes whose discriminatory capability strongly implicates their potential
roles in human atherosclerosis. To improve our understanding of the
genetic factors that influence atherosclerosis, we performed a genomic
analysis of fresh human aorta. We have identified unique gene expression
phenotypes that define disease state and, potentially, disease susceptibility,
and we have generated a novel list of candidate genes for further
study.},
url = {http://atvb.ahajournals.org/cgi/content/abstract/24/10/1922}
}
@ARTICLE{Seo2011,
author = {Seo, Eunjeong and Basu-Roy, Upal and Zavadil, Jiri and Basilico,
Claudio and Mansukhani, Alka},
title = {Distinct Functions of Sox2 Control Self-Renewal and Differentiation
in the Osteoblast Lineage},
journal = {Mol. Cell. Biol.},
year = {2011},
volume = {31},
pages = {4593-4608},
number = {22},
abstract = {The transcription factor Sox2 is a key player in the maintenance of
pluripotency and "stemness." We have previously shown that Sox2 maintains
self-renewal in the osteoblast lineage while inhibiting differentiation
(U. Basu-Roy et al., Cell Death Differ. 17:1345-1353, 2010; A. Mansukhani,
D. Ambrosetti, G. Holmes, L. Cornivelli, and C. Basilico, J. Cell
Biol. 168:1065-1076, 2005). Sox2 also interferes with Wnt signaling
by binding {beta}-catenin, a central mediator of the Wnt pathway.
Here we show that these multiple functions of Sox2 are encoded in
distinct domains. The self-renewal function of Sox2 is dependent
on its transcriptional activity and requires both its DNA-binding
and C-terminal activation regions, while only the third C-terminal
transactivation (TA) region is required for binding {beta}-catenin
and interfering with Wnt-induced transcription. The results of gene
expression analysis upon Sox2 deletion strongly support the notion
that Sox2 maintains stemness. We show also that Sox2 suppresses differentiation
by attenuating Wnt signaling by posttranscriptional and transcriptional
mechanisms and that adenomatous polyposis coli (APC) and GSK3{beta},
which are negative regulators of the Wnt pathway, are direct Sox2
targets in osteoblasts. Several genes, such as the FoxP1 and BMI-1
genes, that are associated with stemness are downregulated upon Sox2
inactivation. Constitutive expression of the Polycomb complex member
BMI-1 can bypass the Sox2 requirement for self-renewal but does not
affect differentiation. Our results establish a connection between
Sox2 and BMI-1 in maintaining self-renewal and identify BMI-1 as
a key mediator of Sox2 function.},
doi = {10.1128/MCB.05798-11},
eprint = {http://mcb.asm.org/cgi/reprint/31/22/4593.pdf},
url = {http://mcb.asm.org/cgi/content/abstract/31/22/4593}
}
@ARTICLE{Seo2008,
author = {Seo, Young-Su and Sriariyanun, Malinee and Wang, Li and Pfeiff, Janice
and Phetsom, Jirapa and Lin, Ye and Jung, Ki-Hong and Chou, Hui Hsien
and Bogdanove, Adam and Ronald, Pamela},
title = {A two-genome microarray for the rice pathogens Xanthomonas oryzae
pv. oryzae and X. oryzae pv. oryzicola and its use in the discovery
of a difference in their regulation of hrp genes},
journal = {BMC Microbiology},
year = {2008},
volume = {8},
pages = {99},
number = {1},
abstract = {BACKGROUND:Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola
(Xoc) are bacterial pathogens of the worldwide staple and grass model,
rice. Xoo and Xoc are closely related but Xoo invades rice vascular
tissue to cause bacterial leaf blight, a serious disease of rice
in many parts of the world, and Xoc colonizes the mesophyll parenchyma
to cause bacterial leaf streak, a disease of emerging importance.
Both pathogens depend on hrp genes for type III secretion to infect
their host. We constructed a 50–70 mer oligonucleotide microarray
based on available genome data for Xoo and Xoc and compared gene
expression in Xoo strains PXO99A and Xoc strain BLS256 grown in the
rich medium PSB vs. XOM2, a minimal medium previously reported to
induce hrp genes in Xoo strain T7174.RESULTS:Three biological replicates
of the microarray experiment to compare global gene expression in
representative strains of Xoo and Xoc grown in PSB vs. XOM2 were
carried out. The non-specific error rate and the correlation coefficients
across biological replicates and among duplicate spots revealed that
the microarray data were robust. 247 genes of Xoo and 39 genes of
Xoc were differentially expressed in the two media with a false discovery
rate of 5% and with a minimum fold-change of 1.75. Semi-quantitative-RT-PCR
assays confirmed differential expression of each of 16 genes each
for Xoo and Xoc selected for validation. The differentially expressed
genes represent 17 functional categories.CONCLUSION:We describe here
the construction and validation of a two-genome microarray for the
two pathovars of X. oryzae. Microarray analysis revealed that using
representative strains, a greater number of Xoo genes than Xoc genes
are differentially expressed in XOM2 relative to PSB, and that these
include hrp genes and other genes important in interactions with
rice. An exception was the rax genes, which are required for production
of the host resistance elicitor AvrXa21, and which were expressed
constitutively in both pathovars.},
doi = {10.1186/1471-2180-8-99},
issn = {1471-2180},
pubmedid = {18564427},
url = {http://www.biomedcentral.com/1471-2180/8/99}
}
@ARTICLE{Seok2012,
author = {Seok, Jae Yeon and Na, Deuk Chae and Woo, Hyun Goo and Roncalli,
Massimo and Kwon, So Mee and Yoo, Jeong Eun and Ahn, Ei Young and
Kim, Gwang Il and Choi, Jin-Sub and Kim, Young Bae and Park, Young
Nyun},
title = {A fibrous stromal component in hepatocellular carcinoma reveals a
cholangiocarcinoma-like gene expression trait and EMT},
journal = {Hepatology},
year = {2012},
pages = {n/a--n/a},
abstract = {Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the
major primary liver cancers in adults. The phenotypic overlap between
HCC and CC has been shown to comprise a continuous liver cancer spectrum.
As a proof of this concept, a recent study demonstrated a genomic
subtype of HCC that expressed CC-like gene expression traits such
as CC-like HCC, which revealed the common genomic trait of stem cell-like
properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC),
a rare variant of HCC, is characterized by abundant fibrous stroma
and has been known to express several liver stem/progenitor cell
markers. This suggests that S-HCC may harbor common intermediate
traits between HCC and CC including stem cell traits, which are similar
to those of CC-like HCC. However, the molecular and pathological
characteristics of S-HCC have not been fully evaluated. By performing
gene expression profiling and immunohistochemical evaluation, we
compared the morphological and molecular features of S-HCC with those
of CC and HCC. S-HCC expresses both CC-like and stem cell-like genomic
traits. In addition, we observed the expression of core epithelial-mesenchymal
transition (EMT)-related genes, which may contribute to the aggressive
behavior of S-HCC. Over-expression of transforming growth factor
β (TGF-β) signaling was also found, implying its regulatory role
in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous
stromal component in HCC may contribute to the acquisition of CC-like
gene expression traits in HCC. The expression of stem cell-like traits
and TGF-β/EMT molecules may play a pivotal role in the aggressive
phenotyping of S-HCC. (HEPATOLOGY 2012.)},
doi = {10.1002/hep.25570},
issn = {1527-3350},
keywords = {Scirrhous, Stem, Progenitor, TGF-β, Gene expression profiling},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.25570}
}
@ARTICLE{Seong2009,
author = {Seong, Kye-Yong and Pasquali, Matias and Zhou, Xiaoying and Song,
Jongwoo and Hilburn, Karen and McCormick, Susan and Dong, Yanhong
and Xu, Jin-Rong and Kistler, H. Corby},
title = {Global gene regulation by Fusarium transcription factors Tri6 and
Tri10 reveals adaptations for toxin biosynthesis},
journal = {Molecular Microbiology},
year = {2009},
volume = {72},
pages = {354--367},
number = {2},
abstract = {Summary Trichothecenes are isoprenoid mycotoxins produced in wheat
infected with the filamentous fungus Fusarium graminearum. Some fungal
genes for trichothecene biosynthesis (Tri genes) are known to be
under control of transcription factors encoded by Tri6 and Tri10.
Tri6 and Tri10 deletion mutants were constructed in order to discover
additional genes regulated by these factors in planta. Both mutants
were greatly reduced in pathogenicity and toxin production and these
phenotypes were largely restored by genetic complementation with
the wild-type gene. Transcript levels for over 200 genes were altered
≥ twofold for Δtri6 or Δtri10 mutants including nearly all known
Tri genes. Also reduced were transcript levels for enzymes in the
isoprenoid biosynthetic pathway leading to farnesyl pyrophosphate,
the immediate molecular precursor of trichothecenes. DNA sequences
5′ to isoprenoid biosynthetic genes were enriched for the Tri6p
DNA binding motif, YNAGGCC, in F. graminearum but not in related
species that do not produce trichothecenes. To determine the effect
of trichothecene metabolites on gene expression, cultures were treated
with trichodiene, the first metabolic intermediate specific to the
trichothecene biosynthetic pathway. A total of 153 genes were upregulated
by added trichodiene and were significantly enriched for genes likely
involved in cellular transport. Differentially regulated genes will
be targeted for functional analysis to discover additional factors
involved in toxin biosynthesis, toxin resistance and pathogenesis.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2009.06649.x}
}
@ARTICLE{Seppa2005,
author = {Seppa, Laura and Makarow, Marja},
title = {Regulation and Recovery of Functions of Saccharomyces cerevisiae
Chaperone BiP/Kar2p after Thermal Insult},
journal = {Eukaryot. Cell},
year = {2005},
volume = {4},
pages = {2008--2016},
number = {12},
month = dec,
abstract = {We described earlier a novel mode of regulation of Hsp104, a cytosolic
chaperone directly involved in the refolding of heat-denatured proteins,
and designated it delayed upregulation, or DUR. When Saccharomyces
cerevisiae cells grown at the physiological temperature of 24{degrees}C,
preconditioned at 37{degrees}C, and treated briefly at 50{degrees}C
were shifted back to 24{degrees}C, Hsp104 expression was strongly
induced after 2.5 h of recovery and returned back to normal after
5 h. Here we show that the endoplasmic reticulum (ER) chaperones
BiP/Kar2p and Lhs1p and the mitochondrial chaperone Hsp78 were also
upregulated at the physiological temperature during recovery from
thermal insult. The heat shock element (HSE) in the KAR2 promoter
was found to be sufficient to drive DUR. The unfolded protein element
could also evoke DUR, albeit weakly, in the absence of a functional
HSE. BiP/Kar2p functions in ER translocation and assists protein
folding. Here we found that the synthesis of new BiP/Kar2p molecules
was negligible for more than an hour after the shift of the cells
from 50{degrees}C to 24{degrees}C. Concomitantly, ER translocation
was blocked, suggesting that preexisting BiP/Kar2p molecules or other
necessary proteins were not functioning. Translocation resumed concomitantly
with enhanced synthesis of BiP/Kar2p after 3 h of recovery, after
which ER exit and protein secretion also resumed. For a unicellular
organism like S. cerevisiae, conformational repair of denatured proteins
is the sole survival strategy. Chaperones that refold proteins in
the cytosol, ER, and mitochondria of S. cerevisiae appear to be subject
to DUR to ensure survival after thermal insults.},
url = {http://ec.asm.org/cgi/content/abstract/4/12/2008}
}
@ARTICLE{Sequeira2006,
author = {Sequeira, Adolfo and Gwadry, Fuad G. and ffrench Mullen, Jarlath
M. H. and Canetti, Lilian and Gingras, Yves and Casero, Robert A.,
Jr and Rouleau, Guy and Benkelfat, Chawki and Turecki, Gustavo},
title = {Implication of SSAT by Gene Expression and Genetic Variation in Suicide
and Major Depression},
journal = {Arch Gen Psychiatry},
year = {2006},
volume = {63},
pages = {35--48},
number = {1},
month = jan,
abstract = {Context A large body of evidence suggests that predisposition to suicide,
an important public health problem, is mediated to a certain extent
by neurobiological factors. Objective To investigate patterns of
expression in suicide with and without major depression and to identify
new molecular targets that may play a role in the neurobiology of
these conditions. Design Brain gene expression analysis was performed
using the Affymetrix HG-U133 chipset in the orbital cortex (Brodmann
area [BA] 11), the dorsolateral prefrontal cortex (BA8/9), and motor
cortex (BA4). Subsequent studies were carried out in independent
samples from adjacent areas to validate positive findings, confirm
their relevance at the protein level, and investigate possible effects
of genetic variation. Subjects We investigated 12 psychiatrically
normal control subjects and 24 suicide victims, including 16 with
and 8 without major depression, in the brain gene expression analysis,
validation, and protein studies. The genetic studies included 181
suicide completers and 80 psychiatrically normal controls. All subjects
investigated were male and of French Canadian origin. Main Outcome
Measures Gene expression measures from microarray, semiquantitative
reverse transcription-polymerase chain reaction, immunohistochemistry,
and Western blot analyses. Results Twenty-six genes were selected
because of the consistency of their expression pattern (fold change,
>1.3 in either direction [P[≤].01] in at least 2 regions). The
spermine/spermidine N1-acetyltransferase gene (SSAT) was successfully
validated by reverse transcription-polymerase chain reaction, immunohistochemistry,
and Western blot analyses. A variant located in the SSAT polyamine-responsive
element regulatory region (SSAT342A/C) demonstrated a significant
effect of genotype on SSAT brain expression levels (F1 = 5.34; P
= .02). Further investigation of this variant in an independent sample
of 181 male suicide completers and 80 male controls showed a higher
frequency of the SSAT342C allele among suicide cases (odds ratio,
2.7; 95% confidence interval, 1.4-5.3; P = .005), suggesting that
this allele may increase predisposition to suicide. Conclusions These
data suggest a role for SSAT, the rate-limiting enzyme in the catabolism
of polyamines, in suicide and depression and a role for the SSAT342
locus in the regulation of SSAT gene expression.},
url = {http://archpsyc.ama-assn.org/cgi/content/abstract/63/1/35}
}
@ARTICLE{Serafimidis2008,
author = {Serafimidis, Ioannis and Rakatzi, Irini and Episkopou, Vasso and
Gouti, Mina and Gavalas, Anthony},
title = {Novel Effectors of Directed and Ngn3-Mediated Differentiation of
Mouse Embryonic Stem Cells into Endocrine Pancreas Progenitors},
journal = {STEM CELLS},
year = {2008},
volume = {26},
pages = {3--16},
number = {1},
abstract = {Abstract 10.1634/stemcells.2007-0194.abs The delineation of regulatory
networks involved in early endocrine pancreas specification will
play a crucial role in directing the differentiation of embryonic
stem cells toward the mature phenotype of β cells for cell therapy
of type 1 diabetes. The transcription factor Ngn3 is required for
the specification of the endocrine lineage, but its direct targets
and the scope of biological processes it regulates remain elusive.
We show that stepwise differentiation of embryonic stem cells using
successive in vivo patterning signals can lead to simultaneous induction
of Ptf1a and Pdx1 expression. In this cellular context, Ngn3 induction
results in upregulation of its known direct target genes within 12
hours. Microarray gene expression profiling at distinct time points
following Ngn3 induction suggested novel and diverse roles of Ngn3
in pancreas endocrine cell specification. Induction of Ngn3 expression
results in regulation of the Wnt, integrin, Notch, and transforming
growth factor β signaling pathways and changes in biological processes
affecting cell motility, adhesion, the cytoskeleton, the extracellular
matrix, and gene expression. Furthermore, the combination of in vivo
patterning signals and inducible Ngn3 expression enhances ESC differentiation
toward the pancreas endocrine lineage. This is shown by strong upregulation
of endocrine lineage terminal differentiation markers and strong
expression of the hormones glucagon, somatostatin, and insulin. Importantly,
all insulin+ cells are also C-peptide+, and glucose-dependent insulin
release was 10-fold higher than basal levels. These data suggest
that bona fide pancreas endocrine cells have been generated and that
timely induction of Ngn3 expression can play a decisive role in directing
ESC differentiation toward the endocrine lineage. Disclosure of potential
conflicts of interest is found at the end of this article.},
issn = {1549-4918},
keywords = {Embryonic stem cells, Directed differentiation, Endocrine pancreas,
Microarrays, Gene regulation, Signaling pathways},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-0194}
}
@ARTICLE{Seredkina2011,
author = {Natalya Seredkina and Ole P. Rekvig},
title = {Acquired Loss of Renal Nuclease Activity Is Restricted to DNaseI
and Is an Organ-Selective Feature in Murine Lupus Nephritis},
journal = {The American Journal of Pathology},
year = {2011},
volume = {179},
pages = {1120 - 1128},
number = {3},
abstract = {An acquired loss of renal DNaseI promotes transformation of mild mesangial
lupus nephritis into membranoproliferative end-stage organ disease.
In this study, we analyzed expression profiles of DNaseI in other
organs of lupus-prone (NZB×NZW)F1 mice during disease progression
to determine whether silencing of the renal DNaseI gene is an organ-specific
feature or whether loss of DNaseI reflects a systemic error in mice
with sever lupus nephritis. The present results demonstrate normal
or elevated levels of DNaseI mRNA and enzyme activity in liver, spleen,
and serum samples from (NZB×NZW)F1 mice throughout all the stages
of lupus nephritis. DNaseI activity was dramatically reduced only
in kidneys of mice with sever nephritis and was the only nuclease
that was down-regulated, whereas six other nucleases (DNaseII1 to
3, caspase-activated DNase, Dnase2a, and endonuclease G) were approximately
normally expressed in kidneys, liver, and spleen. Loss of renal DNaseI
was not accompanied by changes in serum DNaseI activity, suggesting
independent mechanisms of DNaseI regulation in circulation and in
kidneys and an absence of compensatory up-regulation of serum DNaseI
activity in the case of renal DNaseI deficiency. Thus, silencing
of renal DNaseI is a unique renal feature in membranoproliferative
lupus nephritis. Determining the mechanism(s) responsible for DNaseI
down-regulation might lead to the generation of new therapeutic targets
to treat and prevent progressive lupus nephritis.},
doi = {10.1016/j.ajpath.2011.05.011},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011005104}
}
@ARTICLE{Seredkina2009,
author = {Seredkina, Natalya and Zykova, Svetlana N. and Rekvig, Ole P.},
title = {Progression of Murine Lupus Nephritis Is Linked to Acquired Renal
Dnase1 Deficiency and Not to Up-Regulated Apoptosis},
journal = {Am. J. Pathol.},
year = {2009},
volume = {175},
pages = {97--106},
number = {1},
month = jul,
abstract = {The accumulation of apoptotic cells has been suggested as a possible
mechanism of nucleosome conversion into self-antigens that may both
initiate autoimmune responses and participate in immune complex deposition
in lupus nephritis. In this study, we analyzed both the rate of transcription
of apoptosis-related genes and the presence of activated apoptotic
factors within kidneys of lupus-prone (NZBxNZW) F1 mice during disease
progression. The results of this study demonstrated no activation
of apoptotic pathways in kidneys of these lupus-prone mice at the
time of appearance of anti-double standard DNA antibodies in serum,
as well as the formation of mesangial immune deposits in glomeruli.
In contrast, the transition of mesangial into membranoproliferative
lupus nephritis coincided with an accumulation of activated caspase
3-positive cells in kidneys, in addition to a dramatic decrease in
Dnase1 gene transcription. Highly reduced expression levels of the
Dnase1 gene may be responsible for the accumulation of large chromatin-containing
immune complexes in glomerular capillary membranes. Thus, the initiation
of lupus nephritis is not linked to increased apoptotic activity
in kidneys. The combined down-regulation of Dnase1 and the increased
number of apoptotic cells, which is possibly due to their reduced
clearance in affected kidneys, may together be responsible for the
transformation of mild mesangial lupus nephritis into severe membranoproliferative,
end-stage organ disease.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/175/1/97}
}
@ARTICLE{Sergent2010,
author = {Sergent, Thérèse and Piront, Neil and Meurice, Julie and Toussaint,
Olivier and Schneider, Yves-Jacques},
title = {Anti-inflammatory effects of dietary phenolic compounds in an in
vitro model of inflamed human intestinal epithelium},
journal = {Chemico-Biological Interactions},
year = {2010},
volume = {188},
pages = {659--667},
number = {3},
month = dec,
abstract = {Phenolic compounds (PCs) are considered to possess anti-inflammatory
properties and therefore were proposed as an alternative natural
approach to prevent or treat chronic inflammatory diseases. However
their effects are not fully understood, particularly at the intestinal
level. To further understand their mode of action at the molecular
level during intestinal inflammation, an in vitro model of inflamed
human intestinal epithelium was established. Different representative
dietary PCs, i.e. resveratrol, ellagic and ferulic acids, curcumin,
quercetin, chrysin, (-)-epigallocatechin-3-gallate (EGCG) and genistein,
were selected. To mimic intestinal inflammation, differentiated Caco-2
cells cultivated in bicameral inserts, in a serum-free medium, were
treated with a cocktail of pro-inflammatory substances: interleukin
(IL)-1[beta], tumor necrosis factor-[alpha], interferon-[gamma] and
lipopolysaccharides. The inflammatory state was characterized by
a leaky epithelial barrier (attenuation of the transepithelial electrical
resistance) and by an over-expression at the mRNA and protein levels
for pro-inflammatory markers, i.e. IL-6, IL-8 and monocyte chemoattractant
protein-1 (MCP-1), quantified by ELISA and by gene expression analysis
using a low-density array allowing the evaluation of expression level
for 46 genes relevant of the intestinal inflammation and functional
metabolism. Treatment with PCs, used at a realistic intestinal concentration,
did not affect cell permeability. In inflamed cells, the incubation
with genistein reduced the IL-6 and MCP-1 overproduction, to ca.
50% of the control, whereas EGCG provoked a decrease in the IL-6
and IL-8 over-secretion, by 50 and 60%, respectively. This occurred
for both flavonoids without any concomitant inhibition of the corresponding
mRNA expression. All the PCs generated a specific gene expression
profile, with genistein the most efficient in the downregulation
of the expression, or over-expression, of inflammatory genes notably
those linked to the arachidonic metabolism pathway. In conclusion,
this study provides evidence that genistein and EGCG downregulate
the inflammatory response in inflamed intestinal epithelial cells
by a pathway implicating largely a post-transcriptional regulatory
mechanism.},
issn = {0009-2797},
keywords = {Intestinal inflammation, Caco-2 cells, Phenolic compounds, Cytokine
secretion, Low-density array, Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0009279710005272}
}
@ARTICLE{Serrano2008,
author = {Serrano, Elena and Carnicer, Maria J. and Lasa, Adriana and Orantes,
Vanesa and Pena, Jorge and Brunet, Salut and Aventín, Anna and Sierra,
Jorge and Nomdedéu, Josep F.},
title = {Epigenetic-based treatments emphasize the biologic differences of
core-binding factor acute myeloid leukemias},
journal = {Leukemia Research},
year = {2008},
volume = {32},
pages = {944--953},
number = {6},
month = jun,
abstract = {Acute myeloid leukemia (AML) is a heterogeneous group of disorders
characterized by an abnormal proliferation of the myeloid precursors
and a maturation block. The most common chromosomal lesions in AML
are the t(8;21) and inv(16). To better understand the leukemogenic
mechanism of these fusion proteins, we performed gene expression
studies in samples from (8;21), AML1 mutated and inv(16) patients,
as well as from the Kasumi-1 cell line and a U937 cell line expressing
the AML1-ETO fusion gene. To assess the influence of associated epigenetic
lesions, we performed gene expression studies in Kasumi-1 cells and
cells extracted from an Inv(16) patient, both treated with demethylating
and HDAC inhibitor agents. Shared deregulated genes in the different
types of core-binding factor leukemias were identified. We found
a tight link between Inv(16) and mutant AML1 samples. Furthermore,
some of the genes deregulated by the leukemogenic process reverted
to their normal expression with demethylating and HDAC inhibitor
treatment, highlighting the role of chromatin remodeling processes
in AML.},
issn = {0145-2126},
keywords = {Expression profiling, AML1 gene mutation, AML1-ETO fusion gene, Acute
myeloid leukemia, Microarrays},
url = {http://www.sciencedirect.com/science/article/B6T98-4RWK070-2/2/c31ed323a02b216c9e1936802126d06c}
}
@ARTICLE{Serrano2007,
author = {Serrano, Laetitia and Halanych, Kenneth M. and Henry, Raymond P.},
title = {Salinity-stimulated changes in expression and activity of two carbonic
anhydrase isoforms in the blue crab Callinectes sapidus},
journal = {J. Exp. Biol.},
year = {2007},
volume = {210},
pages = {2320--2332},
number = {13},
month = jul,
abstract = {Two isoforms of the enzyme carbonic anhydrase (CA) in the blue crab
gill, CasCAg and CasCAc, were identified, sequenced, and found to
match the membrane-associated and cytoplasmic isoforms, respectively.
The membrane-associated isoform is present in much higher levels
of mRNA expression in both anterior and posterior gills in crabs
acclimated to high salinity (35 p.p.t.), but expression of the cytoplasmic
isoform in the posterior gill undergoes a significantly greater degree
of up-regulation after exposure to low salinity (15 p.p.t.). CasCAc
has the largest scope of induction (100-fold) reported for any transport-related
protein in the gill, and this may be necessary to overcome diffusion
limitations between gill cytoplasm and the apical boundary layer.
Furthermore, the timing of the changes in expression of CasCAc corresponds
to the timing of the induction of protein-specific CA activity and
CA protein concentration. No changes in CA mRNA expression or activity
occur in the anterior gills. The pattern of up-regulation of expression
of mRNA of the {alpha}-subunit of the Na+/K+-ATPase is similar to
that for CasCAc, and both precede the establishment of the new acclimated
physiological state of the crab in low salinity. A putative `housekeeping'
gene, arginine kinase, also showed about a threefold increase in
expression in response to low salinity, but only in the posterior
gills. These results suggest that for studies of expression in crustacean
gill tissue, a control tissue, such as the anterior gill, be used
until an adequate control gene is identified.},
url = {http://jeb.biologists.org/cgi/content/abstract/210/13/2320}
}
@ARTICLE{Serrano2008a,
author = {Serrano, Laetitia and Henry, Raymond P.},
title = {Differential expression and induction of two carbonic anhydrase isoforms
in the gills of the euryhaline green crab, Carcinus maenas, in response
to low salinity},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2008},
volume = {3},
pages = {186--193},
number = {2},
month = jun,
abstract = {Two isoforms of the enzyme carbonic anhydrase (CA) from the gills
of the euryhaline green crab were sequenced and identified; these
were found to match the cytoplasmic (CAc) and membrane-associated
(CAg) isoforms known from other species. The mRNA of the membrane-associated
isoform is present in significantly higher levels of abundance in
gills of crabs acclimated to 32 ppt, at which the crab is an osmotic
and ionic conformer. Upon transfer to low salinity (15 ppt), in which
the crab is an osmoregulator, however, the cytoplasmic isoform undergoes
a rapid 100-fold increase in abundance in the posterior gills, becoming
the dominant isoform. CAg increases 3-fold initially and then remains
elevated through 14 days of low salinity acclimation. The induction
of CAc mRNA is believed to be the molecular basis for the 20 fold
increase in CA protein-specific activity during low salinity acclimation.
The initial increase in CAc mRNA takes place at 6 h, and maximal
levels of expression are achieved by 24 h; this precedes the induction
of CA activity and is within the time in which hemolymph osmotic
and ionic concentrations stabilize at new acclimated levels. The
increase in expression of the CAg isoform is believed to be more
closely related to changes in the population of branchial chloride
cells. Changes in the relative abundance of mRNA for the [alpha]-subunit
of the Na+/K+-ATPase were smaller in magnitude than those for CAc,
but the timing was similar. There were no changes in expression of
a control gene, arginine kinase (AK) in posterior gills, and there
were no significant changes in expression in anterior gills for any
of the genes measured here. These results support the use of a control
tissue (anterior gills) in addition to a control gene for expression
studies.},
issn = {1744-117X},
keywords = {Carbonic anhydrase, Osmoregulation, Crustaceans, Gene expression},
url = {http://www.sciencedirect.com/science/article/B7XM1-4RY6X14-1/2/2c6be4b8a9cf240caff1dca1fc15393f}
}
@ARTICLE{Serrano2007a,
author = {Serrano, L. and Towle, D.W. and Charmantier, G. and Spanings-Pierrot,
C.},
title = {Expression of Na+/K+-ATPase [alpha]-subunit mRNA during embryonic
development of the crayfish Astacus leptodactylus},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2007},
volume = {2},
pages = {126--134},
number = {2},
month = jun,
abstract = {Astacus leptodactylus is a decapod crustacean fully adapted to freshwater
where it spends its entire life cycle after hatching under huge osmoconcentration
differences between the hemolymph and surrounding freshwater. We
investigated the expression of mRNA encoding one ion transport-related
protein, Na+/K+-ATPase [alpha]-subunit, and one putative housekeeping
gene, [beta]-actin, during crayfish ontogenesis using quantitative
real-time PCR. A 216-amino acid part of the open reading frame region
of the cDNA coding for the Na+/K+-ATPase [alpha]-subunit was sequenced
from total embryo, juvenile and adult gill tissues. The predicted
amino acid sequence showed a high percentage similarity to those
of other invertebrates (up to 95%) and vertebrates (up to 69%). [beta]-actin
expression exhibited modest changes through embryonic development
and early post-embryonic stage. The Na+/K+-ATPase [alpha]-subunit
gene was expressed in all studied stages from metanauplius to juvenile.
Two peaks of expression were observed: one in young embryos at 25%
of embryonic development (EI = 100 [mu]m), and one in embryos just
before hatching (at EI = 420 [mu]m), continuing in the freshly hatched
juveniles. The Na+/K+-ATPase expression profile during embryonic
development is time-correlated with the occurrence of other features,
including ontogenesis of excretory antennal glands and differentiation
of gill ionocytes linked to hyperosmoregulation processes and therefore
involved in freshwater adaptation.},
issn = {1744-117X},
keywords = {Astacus leptodactylus, Crustacean, Embryonic development, Na+/K+-ATPase,
Osmoregulation, Real-time PCR},
url = {http://www.sciencedirect.com/science/article/B7XM1-4MYMG41-1/2/c4e8dae07495a6069429b620be5eb54f}
}
@ARTICLE{Serrano2011,
author = {Serrano, Maria J. and So, Sarah and Svoboda, Kathy K.H. and Hinton,
Robert J.},
title = {Cell fate mediators Notch and Twist in mouse mandibular condylar
cartilage},
journal = {Archives of Oral Biology},
year = {2011},
volume = {56},
pages = {607--613},
number = {6},
month = jun,
abstract = {Objective The objectives of this study were to examine if Twist and
Notch 1 are present in the mandibular condylar cartilage (MCC) and
whether their gene expression can be altered by exogenous FGF-2 and
TGF-[beta]2.Design Half-heads from CD-1 mice pups harvested at embryonic
day 17 (E17) were fixed, decalcified, and sectioned in the sagittal
plane for immunohistochemical detection of Notch and Twist using
confocal microscopy. Other mandibular condyles and adjacent ramus
from E17 mice were cultured in serum-free DMEM containing 0, 3, or
30 ng/mL of FGF-2 (10-12 condyles per treatment group). This experimental
design was repeated with medium containing 0, 3, or 30 ng/mL of TGF-[beta]2.
After 3 days of culture, the pooled RNA from each group was extracted
for examination of Notch and Twist gene expression using quantitative
real-time RT-PCR.Results Immunohistochemical examination revealed
that Notch and Twist were localized to the prechondroblastic and
upper chondroblastic layers of the cartilage. Exogenous FGF-2 up-regulated
Notch 1, Twist 1 and Twist 2 gene expression in MCC explants from
E17 mice, whilst TGF-[beta]2 had the opposite effect.Conclusions
The gene expression data demonstrate that MCC explants are sensitive
to growth factors known to affect Notch and Twist in other tissues.
The subset of cells in which Twist and Notch immunoreactivity was
found is suggestive of a role for FGF-2 and TGF-[beta]2 as regulators
of cell differentiation of the bipotent MCC cell population, consistent
with the role of Notch and Twist as downstream mediators of these
growth factors in other tissues.},
issn = {0003-9969},
keywords = {Mandibular condylar cartilage, Notch, Twist},
url = {http://www.sciencedirect.com/science/article/pii/S0003996910003493}
}
@ARTICLE{Serre2010,
author = {Serre, David and Lee, Byron H. and Ting, Angela H.},
title = {MBD-isolated Genome Sequencing provides a high-throughput and comprehensive
survey of DNA methylation in the human genome},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {391--399},
number = {2},
month = jan,
abstract = {DNA methylation is an epigenetic modification involved in both normal
developmental processes and disease states through the modulation
of gene expression and the maintenance of genomic organization. Conventional
methods of DNA methylation analysis, such as bisulfite sequencing,
methylation sensitive restriction enzyme digestion and array-based
detection techniques, have major limitations that impede high-throughput
genome-wide analysis. We describe a novel technique, MBD-isolated
Genome Sequencing (MiGS), which combines precipitation of methylated
DNA by recombinant methyl-CpG binding domain of MBD2 protein and
sequencing of the isolated DNA by a massively parallel sequencer.
We utilized MiGS to study three isogenic cancer cell lines with varying
degrees of DNA methylation. We successfully detected previously known
methylated regions in these cells and identified hundreds of novel
methylated regions. This technique is highly specific and sensitive
and can be applied to any biological settings to identify differentially
methylated regions at the genomic scale.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/2/391}
}
@ARTICLE{Serreze2008,
author = {Serreze, David V. and Choisy-Rossi, Caroline Morgane and Grier, Alexandra
E. and Holl, T. Mathew and Chapman, Harold D. and Gahagan, J. Reed
and Osborne, Melissa A. and Zhang, Weidong and King, Benjamin L.
and Brown, Aaron and Roopenian, Derry and Marron, Michele P.},
title = {Through Regulation of TCR Expression Levels, an Idd7 Region Gene(s)
Interactively Contributes to the Impaired Thymic Deletion of Autoreactive
Diabetogenic CD8+ T Cells in Nonobese Diabetic Mice},
journal = {J. Immunol.},
year = {2008},
volume = {180},
pages = {3250--3259},
number = {5},
month = mar,
abstract = {When expressed in NOD, but not C57BL/6 (B6) genetic background mice,
the common class I variants encoded by the H2g7 MHC haplotype aberrantly
lose the ability to mediate the thymic deletion of autoreactive CD8+
T cells contributing to type 1 diabetes (T1D). This indicated some
subset of the T1D susceptibility (Idd) genes located outside the
MHC of NOD mice interactively impair the negative selection of diabetogenic
CD8+ T cells. In this study, using both linkage and congenic strain
analyses, we demonstrate contributions from a polymorphic gene(s)
in the previously described Idd7 locus on the proximal portion of
Chromosome 7 predominantly, but not exclusively, determines the extent
to which H2g7 class I molecules can mediate the thymic deletion of
diabetogenic CD8+ T cells as illustrated using the AI4 TCR transgenic
system. The polymorphic Idd7 region gene(s) appears to control events
that respectively result in high vs low expression of the AI4 clonotypic
TCR {alpha}-chain on developing thymocytes in B6.H2g7 and NOD background
mice. This expression difference likely lowers levels of the clonotypic
AI4 TCR in NOD, but not B6.H2g7 thymocytes, below the threshold presumably
necessary to induce a signaling response sufficient to trigger negative
selection upon Ag engagement. These findings provide further insight
to how susceptibility genes, both within and outside the MHC, may
interact to elicit autoreactive T cell responses mediating T1D development
in both NOD mice and human patients.},
url = {http://www.jimmunol.org/cgi/content/abstract/180/5/3250}
}
@ARTICLE{Sers2009,
author = {Sers, Christine and Kuner, Ruprecht and Falk, Christine S. and Lund,
Per and Sueltmann, Holger and Braun, Monika and Buness, Andreas and
Ruschhaupt, Markus and Conrad, Janine and Mang-Fatehi, Shila and
Stelniec, Iwona and Krapfenbauer, Ulf and Poustka, Annemarie and
Schäfer, Reinhold},
title = {Down-regulation of HLA Class I and NKG2D ligands through a concerted
action of MAPK and DNA methyltransferases in colorectal cancer cells},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {1626--1639},
number = {7},
abstract = {Abstract 10.1002/ijc.24557.abs Most malignant features of cancer cells
are triggered by activated oncogenes and the loss of tumor suppressors
due to mutation or epigenetic inactivation. It is still unclear,
to what extend the escape of emerging cancer cells from recognition
and elimination by the immune system is determined by similar mechanisms.
We compared the transcriptomes of HCT116 colorectal cancer cells
deficient in DNA methyltransferases (DNMTs) and of cells, in which
the RAS pathway as the major growth-promoting signaling system is
blocked by inhibition of MAPK. We identified the MHC Class I genes
HLA-A1/A2 and the ULBP2 gene encoding 1 of the 8 known ligands of
the activating NK receptor NKG2D among a cluster of immune genes
up-regulated under the conditions of both DNMT-deficiency and MEK-inhibition.
Bisulphite sequencing analyses of HCT116 with DNMT deficiency or
after MEK-inhibition showed that de-methylation of the ULPB2 promoter
correlated with its enhanced surface expression. The HLA-A promoters
were not methylated indicating that components of the HLA assembly
machinery were also suppressed in DNMT-deficient and MEK-inhibited
cells. Increased HLA-A2 surface expression was correlated with enhanced
recognition and lysis by A2-specific CTL. On the contrary, elevated
ULBP2 expression was not reflected by enhanced recognition and lysis
by NK cells. Cosuppression of HLA Class I and NKG2D ligands and genes
encoding peptide transporters or proteasomal genes mediates a strong
functional link between RAS activation, DNMT activity and disruption
of the antigen presenting system controlling immune recognition in
colorectal cancer cells. © 2009 UICC},
issn = {1097-0215},
keywords = {RAS, oncogene, DNA methylation, HLA, immune suppression, signal transduction,
colorectal cancer},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24557}
}
@ARTICLE{SERTEL2011,
author = {SERTEL, SERKAN and EICHHORN, TOLGA and PLINKERT, PETER K. and EFFERTH,
THOMAS},
title = {Chemical Composition and Antiproliferative Activity of Essential
Oil from the Leaves of a Medicinal Herb, Levisticum officinale, against
UMSCC1 Head and Neck Squamous Carcinoma Cells},
journal = {Anticancer Res},
year = {2011},
volume = {31},
pages = {185--191},
number = {1},
month = jan,
abstract = {Background: Oral squamous cell carcinoma (OSCC) is a challenging disease
with a high mortality rate. Natural products represent a valuable
source for the development of novel anticancer drugs. We investigated
the cytotoxic potential of essential oil from the leaves of a medicinal
plant, Levisticum officinale (lovage) on head and neck squamous carcinoma
cells (HNSCC). Materials and Methods: Cytotoxicity of lovage essential
oil was investigated on the HNSCC cell line, UMSCC1. Additionally,
we performed pharmacogenomics analyses. Results: Lovage essential
oil extract had an IC50 value of 292.6 {micro}g/ml. Genes involved
in apoptosis, cancer, cellular growth and cell cycle regulation were
the most prominently affected in microarray analyses. The three pathways
to be most significantly regulated were extracellular signal-regulated
kinase 5 (ERK5) signaling, integrin-linked kinase (ILK) signaling,
virus entry via endocytic pathways and p53 signaling. Conclusion:
Levisticum officinale essential oil inhibits human HNSCC cell growth.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/31/1/185}
}
@ARTICLE{Sertel2011,
author = {Sertel, Serkan And Eichhorn, Tolga And Plinkert, Peter K. And Efferth,
Thomas},
title = {Cytotoxicity of Thymus vulgaris Essential Oil Towards Human Oral
Cavity Squamous Cell Carcinoma},
journal = {Anticancer Res},
year = {2011},
volume = {31},
pages = {81-87},
number = {1},
abstract = {Background: Oral cavity squamous cell carcinoma (OCSCC) accounts for
2% to 3% of all malignancies and has a high mortality rate. The majority
of anticancer drugs are of natural origin. However, it is unknown
whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic
towards head and neck squamous cell carcinoma (HNSCC). Materials
and Methods: Cytotoxicity of thyme essential oil was investigated
on the HNSCC cell line, UMSCC1. The IC50 of thyme essential oil extract
was 369 {micro}g/ml. Moreover, we performed pharmacogenomics analyses.
Results: Genes involved in the cell cycle, cell death and cancer
were involved in the cytotoxic activity of thyme essential oil at
the transcriptional level. The three most significantly regulated
pathways by thyme essential oil were interferon signaling, N-glycan
biosynthesis and extracellular signal-regulated kinase 5 (ERK5) signaling.
Conclusion: Thyme essential oil inhibits human HNSCC cell growth.
Based on pharmacogenomic approaches, novel insights into the molecular
mode of anticancer activity of thyme are presented.},
eprint = {http://ar.iiarjournals.org/cgi/reprint/31/1/81.pdf},
url = {http://ar.iiarjournals.org/cgi/content/abstract/31/1/81}
}
@ARTICLE{Serteyn2010,
author = {Serteyn, Didier and Piquemal, David and Vanderheyden, Laurent and
Lejeune, Jean-Philippe and Verwilghen, Denis and Sandersen, Charlotte},
title = {Gene expression profiling from leukocytes of horses affected by osteochondrosis},
journal = {J. Orthop. Res.},
year = {2010},
volume = {28},
pages = {965--970},
number = {7},
abstract = {Abstract 10.1002/jor.21089.abs Osteochondrosis (OC) is a developmental
disease that affects growing horses and that severely affects their
ability to perform. The genetic basis of its pathogenesis is poorly
understood. The aim of the study was to analyze the transcript profile
of leukocytes from horses affected with OC. Two transcriptome libraries
were constructed from leukocytes of OC-affected and non–OC-affected
horses using digital gene expression analysis (DGE) and real-time
PCR. Statistical analysis allowed selection of 1,008 tags upregulated
in the non–OC-affected group and 1,545 tags upregulated in the
OC-affected group. Among these genes, 16 regulated genes and 5 housekeeping
genes were selected. Metabolic pathways analysis showed an obvious
dysregulation of several signaling pathways related to cartilage
formation or cartilage repair, including Wnt, Indian hedgehog, and
TGF-beta signaling. Other genes, including ISG, ApoB, MGAT4, and
TBC1D9, showed a significantly different expression between groups.
These genes may play a role in high carbohydrate diet, abnormal insulin
metabolism, or inflammation, mechanisms suspected to be involved
in OC. This DGE analysis of the transcript profile of leukocytes
from OC-affected horses demonstrated significant differences in comparison
to the control library. These results open new perspectives for the
understanding of equine OC. © 2010 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 28:965–970, 2010},
issn = {1554-527X},
keywords = {equine, osteochondrosis, digital gene expression analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jor.21089}
}
@ARTICLE{Servinsky2010,
author = {Servinsky, Matthew D. and Kiel, James T. and Dupuy, Nicole F. and
Sund, Christian J.},
title = {Transcriptional analysis of differential carbohydrate utilization
by Clostridium acetobutylicum},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {3478--3491},
number = {11},
month = nov,
abstract = {Transcriptional analysis was performed on Clostridium acetobutylicum
with the goal of identifying sugar-specific mechanisms for the transcriptional
regulation of transport and metabolism genes. DNA microarrays were
used to determine transcript levels from total RNA isolated from
cells grown on media containing eleven different carbohydrates, including
two pentoses (xylose, arabinose), four hexoses (glucose, mannose,
galactose, fructose), four disaccharides (sucrose, lactose, maltose,
cellobiose) and one polysaccharide (starch). Sugar-specific induction
of many transport and metabolism genes indicates that these processes
are regulated at the transcriptional level and are subject to carbon
catabolite repression. The results show that C. acetobutylicum utilizes
symporters and ATP-binding cassette (ABC) transporters for the uptake
of pentose sugars, while disaccharides and hexoses are primarily
taken up by phosphotransferase system (PTS) transporters and a gluconate
: H+ (GntP) transporter. The transcription of some transporter genes
was induced by specific sugars, while others were induced by a subset
of the sugars tested. Sugar-specific transport roles are suggested,
based on expression comparisons, for various transporters of the
PTS, the ABC superfamily and members of the major facilitator superfamily
(MFS), including the GntP symporter family and the glycoside-pentoside-hexuronide
(GPH)-cation symporter family. Additionally, updates to the C. acetobutylicum
genome annotation are proposed, including the identification of genes
likely to encode proteins involved in the metabolism of arabinose
and xylose via the pentose phosphate pathway.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/11/3478}
}
@ARTICLE{Servitja2009,
author = {Servitja, Joan-Marc and Pignatelli, Miguel and Maestro, Miguel Angel
and Cardalda, Carina and Boj, Sylvia F. and Lozano, Juanjo and Blanco,
Enrique and Lafuente, Amalia and McCarthy, Mark I. and Sumoy, Lauro
and Guigo, Roderic and Ferrer, Jorge},
title = {Hnf1{alpha} (MODY3) Controls Tissue-Specific Transcriptional Programs
and Exerts Opposed Effects on Cell Growth in Pancreatic Islets and
Liver},
journal = {Mol. Cell. Biol.},
year = {2009},
volume = {29},
pages = {2945--2959},
number = {11},
month = jun,
abstract = {Heterozygous HNF1A mutations cause pancreatic-islet {beta}-cell dysfunction
and monogenic diabetes (MODY3). Hnf1{alpha} is known to regulate
numerous hepatic genes, yet knowledge of its function in pancreatic
islets is more limited. We now show that Hnf1a deficiency in mice
leads to highly tissue-specific changes in the expression of genes
involved in key functions of both islets and liver. To gain insights
into the mechanisms of tissue-specific Hnf1{alpha} regulation, we
integrated expression studies of Hnf1a-deficient mice with identification
of direct Hnf1{alpha} targets. We demonstrate that Hnf1{alpha} can
bind in a tissue-selective manner to genes that are expressed only
in liver or islets. We also show that Hnf1{alpha} is essential only
for the transcription of a minor fraction of its direct-target genes.
Even among genes that were expressed in both liver and islets, the
subset of targets showing functional dependence on Hnf1{alpha} was
highly tissue specific. This was partly explained by the compensatory
occupancy by the paralog Hnf1{beta} at selected genes in Hnf1a-deficient
liver. In keeping with these findings, the biological consequences
of Hnf1a deficiency were markedly different in islets and liver.
Notably, Hnf1a deficiency led to impaired large-T-antigen-induced
growth and oncogenesis in {beta} cells yet enhanced proliferation
in hepatocytes. Collectively, these findings show that Hnf1{alpha}
governs broad, highly tissue-specific genetic programs in pancreatic
islets and liver and reveal key consequences of Hnf1a deficiency
relevant to the pathophysiology of monogenic diabetes.},
url = {http://mcb.asm.org/cgi/content/abstract/29/11/2945}
}
@ARTICLE{Seseke2004,
author = {Seseke, Florian and Thelen, Paul and Ringert, Rolf-Hermann},
title = {Characterization of an Animal Model of Spontaneous Congenital Unilateral
Obstructive Uropathy by cDNA Microarray Analysis},
journal = {European Urology},
year = {2004},
volume = {45},
pages = {374--381},
number = {3},
month = mar,
abstract = {Introduction: The pathophysiology of congenital obstructive uropathy
has been studied intensively in several animal models. A reliable
parameter for early detection of relevant obstruction is not yet
identified. For further investigation of the complex regulatory events
of obstructive uropathy, we used a cDNA microarray technology for
a parallel differential expression analysis of about 15000 different
genes of obstructed, contralateral and healthy kidneys of rats with
spontaneous congenital obstructive uropathy. Methods: Total cellular
RNA of obstructed, contralateral and healthy control kidneys of 32-35
days old rats was extracted and pooled. RNA quality and quantity
was assessed using a Bioanalyzer 2100. mRNA expression for selected
marker genes was assessed by real time PCR. High throughput gene
expression profiling was performed with cDNA microarrays with differentially
labeled cDNA targets. Results: Beside expected typical alterations
of several growth factors such as TGF-[beta], EGF, IGF-1, PDGF, we
observed overexpression of extracellular matrix proteins and a decreased
activity of antioxidant enzymes. Additionally, NF[kappa]B, a nuclear
transcription factor involved in the development of interstitial
fibrosis, was slightly up-regulated in the obstructed kidneys. Down-regulation
of genes involved in tubular sodium transport indicated impaired
concentration ability of the obstructed kidneys. Furthermore, we
found up-regulation of pro-apoptotic genes including transcripts
for the proapoptotic protein Siva. Interestingly, TNF[alpha], another
factor involved in the pathophysiology of congenital obstructive
uropathy, was not differentially regulated. Conclusions: The alterations
of the genes for growth factors, extracellular matrix proteins, antioxidant
enzymes, sodium transport and genes involved in apoptosis support
the representative character of this animal model for congenital
obstructive uropathy. In the rather advanced stage of congenital
renal obstruction a possible explanation of the lacking differential
regulation of TNF[alpha] highlights it as a possible marker of earlier
stages of obstruction. Furthermore, the possible involvement of the
Siva/CD27 pathway in the apoptotic cascade also offers a new possibility
to find a sensitive marker to detect renal obstruction already in
an earlier stage.},
issn = {0302-2838},
keywords = {Obstructive uropathy, cDNA array, Animal model, Growth factors, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6X10-49YH3PT-2/2/4e75bd2c72f824e3df685f4f2b4fc01f}
}
@ARTICLE{Seta2009,
author = {Seta, Francesca and Chung, Andrew D. and Turner, Patricia V. and
Mewburn, Jeffrey D. and Yu, Ying and Funk, Colin D.},
title = {Renal and cardiovascular characterization of COX-2 knockdown mice},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2009},
volume = {296},
pages = {R1751--1760},
number = {6},
month = jun,
abstract = {Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) increase the
incidence of cardiovascular and cerebrovascular events. Complete
disruption of the murine gene encoding COX-2 (Ptgs2) leads to renal
developmental problems, as well as female reproductive anomalies
and patent ductus arteriosus of variable penetrance in newborns,
thus rendering this genetic approach difficult to compare with coxib
administration. Here, we created hypomorphic Ptgs2 (COX-2Neo/Neo)
mice in which COX-2 expression is suppressed to an extent similar
to that achieved with coxibs, but not eliminated, in an attempt to
circumvent these difficulties. In LPS-challenged macrophages and
cytokine-stimulated endothelial cells obtained from COX-2Neo/Neo
mice, COX-2 expression was reduced 70-90%, and these mice developed
a mild renal phenotype compared with COX-2 mice possessing an active
site mutation (COX-2Y385F/Y385F), with minimal signs of renal dysfunction
as measured by FITC-inulin clearance and blood urea nitrogen. These
COX-2 knockdown mice displayed an increased propensity for thrombogenesis
compared with their wild-type (COX-2+/+) littermates observed by
intravital microscopy in cremaster muscle arterioles upon ferric
chloride challenge. Measurement of urinary prostanoid metabolites
indicated that COX-2Neo/Neo mice produced 50% less prostacyclin but
similar levels of PGE2 and thromboxane compared with COX-2+/+ mice
in the absence of any blood pressure and ex vivo platelet aggregation
abnormalities. COX-2Neo/Neo mice, therefore, provide a genetic surrogate
of coxib therapy with disrupted prostacyclin biosynthesis that predisposes
to induced arterial thrombosis.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/296/6/R1751}
}
@ARTICLE{Seta2004,
author = {Seta, Karen A. and Ferguson, Tsuneo K. and Millhorn, David E.},
title = {Discovery of Oxygen-Responsive Genes in Pheochromocytoma Cells},
journal = {Methods Enzymol},
year = {2004},
volume = {Volume 381},
pages = {449--464},
booktitle = {Oxygen Sensing},
editor = {Sen, Chandan K. and Semenza, Gregg L.},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B7CV2-4C47J7W-1Y/2/a6c565290457c35f06a0d665fff7db34}
}
@ARTICLE{Seth2006,
author = {Seth, Devanshi and Gorrell, Mark D. and Cordoba, Shaun and McCaughan,
Geoffrey W. and Haber, Paul S.},
title = {Intrahepatic gene expression in human alcoholic hepatitis},
journal = {Journal of Hepatology},
year = {2006},
volume = {45},
pages = {306--320},
number = {2},
month = aug,
abstract = {Background/Aims Alcoholic hepatitis remains an important cause of
morbidity and mortality. Treatment remains unsatisfactory, in part,
due to limited understanding of the pathogenesis. The aim of this
study is to define the global intrahepatic expression profile of
human alcoholic hepatitis.Methods Gene expression was analysed by
DNA microarray on RNA isolated from liver of patients with alcoholic
hepatitis (AH, n = 8), alcoholic steatosis (AS, n = 9) and explants
from non-diseased donor liver controls (ND, n = 7). Differential
expression of selected genes was confirmed by real-time RT-PCR and
immunohistochemistry.Results Cluster analysis allowed differentiation
of alcoholic hepatitis from alcoholic steatosis. The gene expression
profile of AH revealed 586 genes differentially expressed from AS
and 211 genes differentially expressed from that of ND liver. In
comparison, only 98 genes were differentially expressed in AS from
ND. Novel differentially expressed genes in AH in comparison to ND
and AS included claudins, osteopontin, CD209, selenoprotein and genes
related to bile duct proliferation. Real-time RT-PCR confirmed up-regulation
of IL-8, osteopontin, and TNFRSF14 and down-regulation of SAMeS and
CD209.Conclusions This study has defined the intrahepatic gene expression
profile of human alcoholic hepatitis and revealed a number of novel
differentially expressed genes.},
issn = {0168-8278},
keywords = {Cirrhosis, Fibrogenesis, Annexin A2, CD209, Osteopontin},
url = {http://www.sciencedirect.com/science/article/B6W7C-4K425VC-1/2/15b61d16c2a7dae66341e4f42abd386a}
}
@ARTICLE{Seth2011,
author = {Seth, Shaguna and Matsui, Yoshiyuki and Fosnaugh, Kathy and Liu,
Yan and Vaish, Narendra and Adami, Roger and Harvie, Pierrot and
Johns, Rachel and Severson, Gregory and Brown, Tod and Takagi, Akihide
and Bell, Susan and Chen, Yan and Chen, Feng and Zhu, Tianying and
Fam, Renata and Maciagiewicz, Iwona and Kwang, Erin and McCutcheon,
Michael and Farber, Ken and Charmley, Patrick and Houston Jr., Michael
E and So, Alan and Templin, Michael V and Polisky, Barry},
title = {RNAi-based Therapeutics Targeting Survivin and PLK1 for Treatment
of Bladder Cancer},
journal = {Mol Ther},
year = {2011},
volume = {19},
pages = {928--935},
number = {5},
month = may,
issn = {1525-0016},
publisher = {The American Society of Gene \& Cell Therapy},
url = {http://dx.doi.org/10.1038/mt.2011.21}
}
@ARTICLE{Sethi2011,
author = {Sethi, Nilay and Dai, Xudong and Winter, Christopher G. and Kang,
Yibin},
title = {Tumor-Derived Jagged1 Promotes Osteolytic Bone Metastasis of Breast
Cancer by Engaging Notch Signaling in Bone Cells},
journal = {Cancer Cell},
year = {2011},
volume = {19},
pages = {192--205},
number = {2},
month = feb,
abstract = {Summary Despite evidence supporting an oncogenic role in breast cancer,
the Notch pathway's contribution to metastasis remains unknown. Here,
we report that the Notch ligand Jagged1 is a clinically and functionally
important mediator of bone metastasis by activating the Notch pathway
in bone cells. Jagged1 promotes tumor growth by stimulating IL-6
release from osteoblasts and directly activates osteoclast differentiation.
Furthermore, Jagged1 is a potent downstream mediator of the bone
metastasis cytokine TGF[beta] that is released during bone destruction.
Importantly, [gamma]-secretase inhibitor treatment reduces Jagged1-mediated
bone metastasis by disrupting the Notch pathway in stromal bone cells.
These findings elucidate a stroma-dependent mechanism for Notch signaling
in breast cancer and provide rationale for using [gamma]-secretase
inhibitors for the treatment of bone metastasis.PaperClip},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/pii/S1535610810005313}
}
@ARTICLE{Sethi2009,
author = {Sethi, Prerna and Lukiw, Walter J.},
title = {Micro-RNA abundance and stability in human brain: Specific alterations
in Alzheimer's disease temporal lobe neocortex},
journal = {Neuroscience Letters},
year = {2009},
volume = {459},
pages = {100--104},
number = {2},
month = aug,
abstract = {Micro-RNA (miRNA) mediated regulation of messenger RNA (mRNA) complexity
in the central nervous system (CNS) is emerging as a critical factor
in the control of CNS-specific gene expression during development,
plasticity, aging and disease. In these studies, miRNA array and
Northern blot based tracking of specific miRNA abundances and decay
kinetics in human neural (HN) cells in primary culture and in short
post-mortem interval (PMI, ~1 h) human brain tissues showed a limited
stability and relatively short half-life (~1-3.5 h) for specific
brain-enriched miRNAs. In short PMI Alzheimer's disease (AD)-affected
temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were
found to be significantly up-regulated, an effect that was not seen
in several related neurological disorders. The results suggest (a)
that unless specifically stabilized, certain brain-enriched miRNAs
represent a rapidly executed signaling system employing highly transient
effectors of CNS gene expression, and (b) that in AD temporal lobe
neocortex specific brain miRNAs are significantly up-regulated in
abundance and strongly correlate with the presence of AD-type neuropatholgical
change.},
issn = {0304-3940},
keywords = {[alpha]-Amanitin, Amyotrophic lateral sclerosis (ALS), AREs (AU-rich
elements), Chromatin structure, Depolymerization, Half-life, Human
brain cells, Human brain tissues, Micro-RNA, miRNA, Parkinson's disease,
Schizophrenia, Transcription factors},
url = {http://www.sciencedirect.com/science/article/B6T0G-4W6X9MS-2/2/7c633487282a915c6f20b9025dab2c8b}
}
@ARTICLE{Sethu2006,
author = {Sethu, Palaniappan and Moldawer, Lyle L. and Mindrinos, Michael N.
and Scumpia, Philip O. and Tannahill, Cynthia L. and Wilhelmy, Julie
and Efron, Philip A. and Brownstein, Bernard H. and Tompkins, Ronald
G. and Toner, Mehmet},
title = {Microfluidic Isolation of Leukocytes from Whole Blood for Phenotype
and Gene Expression Analysis},
journal = {Analytical Chemistry},
year = {2006},
volume = {78},
pages = {5453-5461},
number = {15},
doi = {10.1021/ac060140c},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac060140c},
url = {http://pubs.acs.org/doi/abs/10.1021/ac060140c}
}
@ARTICLE{Sethupathy2007,
author = {Sethupathy, Praveen and Borel, Christelle and Gagnebin, Maryline
and Grant, Gregory R. and Deutsch, Samuel and Elton, Terry S. and
Hatzigeorgiou, Artemis G. and Antonarakis, Stylianos E.},
title = {Human microRNA-155 on Chromosome 21 Differentially Interacts with
Its Polymorphic Target in the AGTR1 3' Untranslated Region: A Mechanism
for Functional Single-Nucleotide Polymorphisms Related to Phenotypes},
journal = {The American Journal of Human Genetics},
year = {2007},
volume = {81},
pages = {405--413},
number = {2},
month = aug,
abstract = {Animal microRNAs (miRNAs) regulate gene expression through base pairing
to their targets within the 3' untranslated region (UTR) of protein-coding
genes. Single-nucleotide polymorphisms (SNPs) located within such
target sites can affect miRNA regulation. We mapped annotated SNPs
onto a collection of experimentally supported human miRNA targets.
Of the 143 experimentally supported human target sites, 9 contain
12 SNPs. We further experimentally investigated one of these target
sites for hsa-miR-155, within the 3' UTR of the human AGTR1 gene
that contains SNP rs5186. Using reporter silencing assays, we show
that hsa-miR-155 down-regulates the expression of only the 1166A,
and not the 1166C, allele of rs5186. Remarkably, the 1166C allele
has been associated with hypertension in many studies. Thus, the
1166C allele may be functionally associated with hypertension by
abrogating regulation by hsa-miR-155, thereby elevating AGTR1 levels.
Since hsa-miR-155 is on chromosome 21, we hypothesize that the observed
lower blood pressure in trisomy 21 is partially caused by the overexpression
of hsa-miR-155 leading to allele-specific underexpression of AGTR1.
Indeed, we have shown in fibroblasts from monozygotic twins discordant
for trisomy 21 that levels of AGTR1 protein are lower in trisomy
21.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4R1VX4P-R/2/583e25bd26bb94251cfe17602b34b8fc}
}
@ARTICLE{Setiawan2010,
author = {Setiawan, Alvin and Lokman, P Mark},
title = {The use of reference gene selection programs to study the silvering
transformation in a freshwater eel Anguilla australis: a cautionary
tale},
journal = {BMC Molecular Biology},
year = {2010},
volume = {11},
pages = {75},
number = {1},
abstract = {BACKGROUND:Quantitative real-time PCR (qPCR) has been the method of
choice for the quantification of mRNA. Due to the various artifactual
factors that may affect the accuracy of qPCR, internal reference
genes are most often used to normalize qPCR data. Recently, many
studies have employed computer programs such as GeNorm, BestKeeper
and NormFinder in selecting reference genes, but very few statistically
validate the outcomes of these programs. Thus, in this study, we
selected reference genes for qPCR of liver and ovary samples of yellow
(juvenile), migratory (silver) and 11-KT treated juveniles of New
Zealand shortfinned eels (Anguilla australis) using the three computer
programs and validate the selected genes statistically using REST
2009 software and the Mann-Whitney test. We also tested for the repeatability
of use for the best reference genes by applying them to a data set
obtained in a similar experiment conducted the previous year.RESULTS:Out
of six candidate genes, the combination of 18 s and eef1 was found
to be the best statistically validated reference for liver, while
in ovary it was l36. However, discrepancies in gene rankings were
found between the different programs. Also, statistical validation
procedures showed that several genes put forward as being the best
by the programs were in fact, regulated, making them unsuitable as
reference genes. Additionally, eef1 which was found to be a suitable
- though not the top ranked - reference gene for liver tissues in
one year, was regulated in another.CONCLUSIONS:Our study highlights
the need for external validations of reference gene selections made
by computer programs. Researchers need to be vigilant in validating
and reporting the rationale for the use of reference gene in published
studies.},
doi = {10.1186/1471-2199-11-75},
issn = {1471-2199},
pubmedid = {20860839},
url = {http://www.biomedcentral.com/1471-2199/11/75}
}
@ARTICLE{Setzer2009,
author = {Setzer, Bernhard and Bächle, Maria and Metzger, Marc C. and Kohal,
Ralf J.},
title = {The gene-expression and phenotypic response of hFOB 1.19 osteoblasts
to surface-modified titanium and zirconia},
journal = {Biomaterials},
year = {2009},
volume = {30},
pages = {979--990},
number = {6},
month = feb,
abstract = {The osteoblastic cell-line hFOB 1.19 with the potential to proliferate
and differentiate revealed that cellular differentiation is not affected
by material and roughness on newly developed zirconia implant materials.
Materials under investigation were surfaces machined titanium (Ti-m),
modified titanium (TiUnite®), machined zirconia (TZP-A-m), modified
zirconia (ZiUnite®), machined alumina-toughened zirconia (ATZ-m)
and modified alumina-toughened zirconia (ATZ-mod). After surface
description by scanning electron microscopy (SEM) and atomic force
microscopy (AFM), cellular proliferation (EZ4U, Casy1) and differentiation
were examined after days 1, 3, 7, 14, 21, and 28. Osteogenic differentiation
was visualized by alkaline phosphatase staining, mineralization assay
(alizarin red) and by expression analysis (RT-PCR) of bone- and extracellular
matrix-related genes. Proliferation on rough surfaces was reduced
on both titanium and zirconia. Cell-attachment and cytoskeleton organization
documented by confocal laser scanning microscopy (CLSM) elucidated
attenuated cell attachment within the first 4 h to be the reason
for impaired proliferation. A specific up-regulation of m-RNAs in
an early event (RUNX2, NELL-1, RUNX3, and BMP7) and a late event
(Integrin B3) could be observed on TiUnite® and ZiUnite®. For titanium
an up-regulation of IBSP and Integrin B1 could be described at day
21. In total, differentiation was neither affected by material nor
by roughness.},
issn = {0142-9612},
keywords = {Zirconia, hFOB 1.19, Cell differentiation, RT-PCR, SEM, CLSM},
url = {http://www.sciencedirect.com/science/article/B6TWB-4V053G0-B/2/7d919a7ced63774951303f7f5fe1acd9}
}
@ARTICLE{Setzer2008,
author = {Setzer, Bernhard and Lebrecht, Dirk and Walker, Ulrich A.},
title = {Pyrimidine Nucleoside Depletion Sensitizes to the Mitochondrial Hepatotoxicity
of the Reverse Transcriptase Inhibitor Stavudine},
journal = {Am. J. Pathol.},
year = {2008},
volume = {172},
pages = {681--690},
number = {3},
month = mar,
abstract = {Stavudine is a hepatotoxic antiretroviral nucleoside analogue that
also inhibits the replication of mitochondrial DNA (mtDNA). To elucidate
the mechanism and consequences of mtDNA depletion, we treated HepG2
cells with stavudine and either redoxal, an inhibitor of de novo
pyrimidine synthesis, or uridine, from which pyrimidine pools are
salvaged. Compared with treatment with stavudine alone, co-treatment
with redoxal accelerated mtDNA depletion, impaired cell division,
and activated caspase 3. These adverse effects were completely abrogated
by uridine. Intracellular ATP levels were unaffected. Transcriptosome
profiling demonstrated that redoxal and stavudine acted synergistically
to induce CDKN2A and p21, indicating cell cycle arrest in G1, as
well as genes involved in intrinsic and extrinsic apoptosis. Moreover,
redoxal and stavudine showed synergistic interaction in the up-regulation
of transcripts encoded by mtDNA and the induction of nuclear transcripts
participating in energy metabolism, mitochondrial biogenesis, oxidative
stress, and DNA repair. Genes involved in nucleotide metabolism were
also synergistically up-regulated by both agents; this effect was
completely antagonized by uridine. Thus, pyrimidine depletion sensitizes
cells to stavudine-mediated mtDNA depletion and enhances secondary
cell toxicity. Our results indicate that drugs that diminish pyrimidine
pools should be avoided in stavudine-treated human immunodeficiency
virus patients. Uridine supplementation reverses this toxicity and,
because of its good tolerability, has potential clinical value for
the treatment of side effects associated with pyrimidine depletion.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/172/3/681}
}
@ARTICLE{Sevastianova2011,
author = {Sevastianova, Ksenia and Sutinen, Jussi and Greco, Dario and Sievers,
Meline and Salmenkivi, Kaisa and Perttila, Julia and Olkkonen, Vesa
M. and Wagsater, Dick and Lidell, Martin E. and Enerback, Sven and
Eriksson, Per and Walker, Ulrich A. and Auvinen, Petri and Ristola,
Matti and Yki-Jarvinen, Hannele},
title = {Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue
in Patients With and Without Antiretroviral Therapy-Associated Lipodystrophy},
journal = {Diabetes},
year = {2011},
volume = {60},
pages = {1894-1900},
number = {7},
abstract = {OBJECTIVECombination antiretroviral therapy (cART) is associated with
lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen,
limbs, and face and its accumulation intra-abdominally. No fat is
lost dorsocervically and it can even accumulate in this region (buffalo
hump). It is unknown how preserved dorsocervical fat differs from
abdominal subcutaneous fat in HIV-1-infected cART-treated patients
with (cART+LD+) and without (cART+LD-) lipodystrophy. RESEARCH DESIGN
AND METHODSWe used histology, microarray, PCR, and magnetic resonance
imaging to compare dorsocervical and abdominal subcutaneous adipose
tissue in cART+LD+ (n = 21) and cART+LD- (n = 11). RESULTSAlbeit
dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy,
its mitochondrial DNA (mtDNA; copies/cell) content was significantly
lower (by 62%) than that of the corresponding tissue in cART+LD-.
Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory
genes in microarray were significantly lower in dorsocervical versus
abdominal subcutaneous adipose tissue. Genes with the greatest difference
in expression between the two depots were those involved in regulation
of transcription and regionalization (homeobox genes), irrespective
of lipodystrophy status. There was negligible mRNA expression of
uncoupling protein 1, a gene characteristic of brown adipose tissue,
in either depot. CONCLUSIONSBecause mtDNA is depleted even in the
nonatrophic dorsocervical adipose tissue, it is unlikely that the
cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue
is less inflamed than lipoatrophic adipose tissue. It does not resemble
brown adipose tissue. The greatest difference in gene expression
between dorsocervical and abdominal subcutaneous adipose tissue is
in expression of homeobox genes.},
doi = {10.2337/db11-0075},
eprint = {http://diabetes.diabetesjournals.org/cgi/reprint/60/7/1894.pdf},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/60/7/1894}
}
@ARTICLE{Severa2007,
author = {Severa, Martina and Remoli, Maria Elena and Giacomini, Elena and
Annibali, Viviana and Gafa, Valerie and Lande, Roberto and Tomai,
Mark and Salvetti, Marco and Coccia, Eliana M.},
title = {Sensitization to TLR7 Agonist in IFN-beta-Preactivated Dendritic
Cells},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {6208--6216},
number = {10},
month = may,
abstract = {TLRs interact with a growing list of pathogen-derived products and
these interactions drive the activation of innate and adaptive immune
responses. Dendritic cells (DC) play a key role in these events expressing
a heterogeneous repertoire of TLRs. We have previously demonstrated
the production of type I IFNs in DC following bacterial infections
and TLR triggering. In this study, we sought to characterize the
transcriptome specifically induced in human DC by IFN-[beta] production
stimulated upon LPS treatment. To this aim, by using cDNA microarrays,
we compared the transcriptome of DC following LPS treatment in the
absence or presence of neutralizing anti-type I IFN Abs. Interestingly,
we found that the expression of TLR7 was induced during LPS-induced
maturation of DC in a type I IFN-dependent manner. The induction
of TLR7 in maturing DC was mainly a consequence of the transcriptional
activity of IRF-1, whose binding site was located within TLR7 promoter.
Moreover, we also demonstrated that "priming" of immature DC, that
usually express TLR8 but not TLR7, with exogenous IFN-[beta] induced
a functionally active TLR7. In fact, treatment with the TLR7-specific
ligand 3M-001 up-regulated the expression of CD83, CD86, and CD38
in IFN-[beta]-primed DC but not in immature DC. Therefore, a robust
enhancement in proinflammatory as well as regulatory cytokines was
observed. These data suggest that TLR4-mediated type I IFN release
activates specific transcription programs in DC amplifying the expression
of pathogen sensors to correctly and combinatorially respond to a
bacterial as well as viral infection.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/10/6208}
}
@ARTICLE{Severgnini2006,
author = {Severgnini, Marco and Bicciato, Silvio and Mangano, Eleonora and
Scarlatti, Francesca and Mezzelani, Alessandra and Mattioli, Michela
and Ghidoni, Riccardo and Peano, Clelia and Bonnal, Raoul and Viti,
Federica and Milanesi, Luciano and De Bellis, Gianluca and Battaglia,
Cristina},
title = {Strategies for comparing gene expression profiles from different
microarray platforms: Application to a case-control experiment},
journal = {Analytical Biochemistry},
year = {2006},
volume = {353},
pages = {43--56},
number = {1},
month = jun,
abstract = {Meta-analysis of microarray data is increasingly important, considering
both the availability of multiple platforms using disparate technologies
and the accumulation in public repositories of data sets from different
laboratories. We addressed the issue of comparing gene expression
profiles from two microarray platforms by devising a standardized
investigative strategy. We tested this procedure by studying MDA-MB-231
cells, which undergo apoptosis on treatment with resveratrol. Gene
expression profiles were obtained using high-density, short-oligonucleotide,
single-color microarray platforms: GeneChip (Affymetrix) and CodeLink
(Amersham). Interplatform analyses were carried out on 8414 common
transcripts represented on both platforms, as identified by LocusLink
ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink
features, respectively. We identified 105 differentially expressed
genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only
9 DEGs were commonly identified by both platforms. Multiple analyses
(BLAST alignment of probes with target sequences, gene ontology,
literature mining, and quantitative real-time PCR) permitted us to
investigate the factors contributing to the generation of platform-dependent
results in single-color microarray experiments. An effective approach
to cross-platform comparison involves microarrays of similar technologies,
samples prepared by identical methods, and a standardized battery
of bioinformatic and statistical analyses.},
issn = {0003-2697},
keywords = {Platform comparison, High-density microarray, Comparison strategy},
url = {http://www.sciencedirect.com/science/article/B6W9V-4JMKP5F-1/2/1e929695ba038c83e1da8f07fc00680f}
}
@ARTICLE{Severin2010,
author = {Severin, Andrew and Woody, Jenna and Bolon, Yung-Tsi and Joseph,
Bindu and Diers, Brian and Farmer, Andrew and Muehlbauer, Gary and
Nelson, Rex and Grant, David and Specht, James and Graham, Michelle
and Cannon, Steven and May, Gregory and Vance, Carroll and Shoemaker,
Randy},
title = {RNA-Seq Atlas of Glycine max: A guide to the soybean transcriptome},
journal = {BMC Plant Biology},
year = {2010},
volume = {10},
pages = {160},
number = {1},
abstract = {BACKGROUND:Next generation sequencing is transforming our understanding
of transcriptomes. It can determine the expression level of transcripts
with a dynamic range of over six orders of magnitude from multiple
tissues, developmental stages or conditions. Patterns of gene expression
provide insight into functions of genes with unknown annotation.RESULTS:The
RNA Seq-Atlas presented here provides a record of high-resolution
gene expression in a set of fourteen diverse tissues. Hierarchical
clustering of transcriptional profiles for these tissues suggests
three clades with similar profiles: aerial, underground and seed
tissues. We also investigate the relationship between gene structure
and gene expression and find a correlation between gene length and
expression. Additionally, we find dramatic tissue-specific gene expression
of both the most highly-expressed genes and the genes specific to
legumes in seed development and nodule tissues. Analysis of the gene
expression profiles of over 2,000 genes with preferential gene expression
in seed suggests there are more than 177 genes with functional roles
that are involved in the economically important seed filling process.
Finally, the Seq-atlas also provides a means of evaluating existing
gene model annotations for the Glycine max genome.CONCLUSIONS:This
RNA-Seq atlas extends the analyses of previous gene expression atlases
performed using Affymetrix GeneChip technology and provides an example
of new methods to accommodate the increase in transcriptome data
obtained from next generation sequencing. Data contained within this
RNA-Seq atlas of Glycine max can be explored at http://www.soybase.org/soyseq.},
doi = {10.1186/1471-2229-10-160},
issn = {1471-2229},
pubmedid = {20687943},
url = {http://www.biomedcentral.com/1471-2229/10/160}
}
@ARTICLE{Severine2005,
author = {Severine, Coulon and Pierre, Saintigny and Bernard, Bazelly and Sylvie,
Ricci and Delphine, Montagnier and Francoise, Le Pimpec-Barthes and
Jean-Luc, Breau and Bernard, Milleron and Jean-Francois, Bernaudin},
title = {Detection of circulating cancer cells by real-time RT-PCR in the
pulmonary vein of patients with non-small cell lung cancer},
journal = {AACR Meeting Abstracts},
year = {2005},
volume = {2005},
pages = {1315-a--},
number = {1},
month = apr,
abstract = {Introduction: Patients with non-small cell lung cancer (NSCLC) have
a high risk of relapse even after complete surgical resection. A
possible explanation is dissemination of cancer cells throughout
the body at the time of surgery. We investigated the primary source
of hematogenous dissemination of cancer cells by studying the pulmonary
venous blood draining the tumor. Material and Methods: Between January
and October 2004, 49 patients with completely resected primary NSCLC
were included in the study. Sixteen milliliters of blood were collected
from the pulmonary vein after vessel ligation. Blood from 25 healthy
volunteers was also collected by venipuncture from the antecubital
vein as negative controls. After erythrocyte lysis, total RNA was
extracted from the cell pellet using the TRIZol reagent (Life Technology,
Inc., Gaithersburg, MD, USA) according to the manufacturer's instructions.
RNA quality and quantity were assessed by capillary electrophoresis-based
labChipRNA (Bioanalyzer, Agilent technology). A real-time reverse
transcription polymerase chain reaction assay using Taqman(R) chemistry
was then performed to detect two validated markers: cytokeratin 19
(CK19) and cytokeratin 7 (CK7) mRNA (Int J Cancer, in press). The
human leucocyte antigen class IC (HLAIC) was used as internal control.
Each amplification of the markers (CK7 and CK19) and HLAIC was performed
in triplicate. The standard curve was performed by serial dilution
of a known number of cells from carcinomatous cell lines (CAPAN I
for CK19 or A549 for CK7) in 5 mL of normal human blood. Samples
were considered positive for threshold cycles under 40 for at least
2 of the triplicates. Results: Circulating tumor cells were detected
in blood samples of 26.5% of patients for the CK9 (11/49) or CK 7
(2/49) markers. No control samples were positive for either of the
two markers. A positive detection was correlated in a multiple logistic
model with age [odds ratio (OR), 1.17; 95 pencent confidence interval
(95% CI), 1.03 to 1.33]; squamous and large cell carcinoma rather
than adenocarcinoma (OR,13.27; 95% CI, 1.49 to 118.50) and stage
(OR, 18.18; 95% CI, 1.70 to 194.95). Moreover a positive detection
was observed in 39% of patients who did not receive neoadjuvant chemotherapy,
whereas only 18% of patients who received neoadjuvant chemotherapy
had detectable circulating tumor cells (p=ns). Conclusion: A significant
percentage (>25%) of patients with resecable NSCLC had detectable
circulating cells expressing CK19 or CK7 mRNA. This detection might
be useful to evaluate the efficacy of neoadjuvant chemotherapy. This
tendency needs to be confirmed in a larger series of patients.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/1315-a}
}
@ARTICLE{Sevetson2004,
author = {Sevetson, Brad and Taylor, Scott and Pan, Yang},
title = {Cbfa1/RUNX2 Directs Specific Expression of the Sclerosteosis Gene
(SOST)},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {13849--13858},
number = {14},
month = apr,
abstract = {Loss-of-function mutations in the sclerosteosis gene (SOST) cause
a rare sclerosing bone dysplasia characterized by skeletal overgrowth.
Cbfa1/RUNX2 is a key transcriptional regulator of osteoblast function.
Here we link these two pathways by demonstrating, via gel shift and
transient transfection analyses, that Cbfa1 binding to the proximal
SOST promoter contributes to differential SOST expression in two
osteosarcoma cell lines. Additionally, an E-box binding motif in
the 1.8-kb proximal SOST promoter appears to be functional in SAOS-2
cells, but does not account for SAOS-specific expression of SOST.
The regulation of SOST expression by Cbfa1 suggests a potential role
for the sclerosteosis gene in homeostatic regulation of osteoblast
differentiation and function. Furthermore, the juxtaposition of Cbfa1,
E-box, and C/EBP binding sites in the SOST proximal promoter bears
an intriguing resemblance to the promoter for osteocalcin, another
osteoblast-specific gene with a loss-of-function phenotype of bone
overgrowth.},
url = {http://www.jbc.org/cgi/content/abstract/279/14/13849}
}
@ARTICLE{Sevilla2010,
author = {Sevilla, Lisa M. and Bayo, Pilar and Latorre, Victor and Sanchis,
Ana and Perez, Paloma},
title = {Glucocorticoid Receptor Regulates Overlapping and Differential Gene
Subsets in Developing and Adult Skin},
journal = {Mol. Endocrinol.},
year = {2010},
volume = {24},
pages = {2166--2178},
number = {11},
month = nov,
abstract = {We have previously shown that the glucocorticoid receptor (GR) is
required for skin homeostasis and epidermal barrier competence. To
understand the transcriptional program by which GR regulates skin
development, we performed a microarray analysis using the skin of
GR-/- and GR+/+ mice of embryonic d 18.5 and identified 442 differentially
expressed genes. Functional clustering demonstrated overrepresentation
of genes involved in ectoderm/epidermis development. We found strong
repression of genes encoding proteins associated with the later stages
of epidermal differentiation, such as several small proline-rich
proteins (Sprrs) and corneodesmosin (Cdsn). This, together with the
up-regulation of genes induced earlier during epidermal development,
including the epithelial-specific gene transcripts E74-like factor
5 (Elf5) and keratin 77 (Krt77), fits with the phenotype of defective
epidermal differentiation observed in the GR-/- mice. We also found
down-regulation of the antimicrobial peptide defensin {beta} 1 (Defb1)
and FK506-binding protein 51 (Fkbp51). Skin developmental expression
profiling of these genes and studies in cultured keratinocytes from
GR-/- and wild type embryos demonstrated that gene regulation occurred
in a cell-autonomous manner. To investigate the consequences of GR
loss in adult epidermis, we generated mice with inducible inactivation
of GR restricted to keratinocytes (K14-cre-ERT2//GRloxP/loxP mice).
K14-cre-ERT2//GRloxP/loxP mice featured thickened skin with increased
keratinocyte proliferation and impaired differentiation. Whereas
Krt77 and Elf5 expression remained unaffected by loss of GR in adult
epidermis, Fkbp51, Sprr2d, and Defb1 were strongly repressed. Importantly,
we have identified both Fkbp51 and Defb1 as direct transcriptional
targets of GR, and we have shown that GR-mediated regulation of these
genes occurs in both developing and adult epidermis. We conclude
that both overlapping and differential GR targets are regulated in
developing vs. adult skin.},
url = {http://mend.endojournals.org/cgi/content/abstract/24/11/2166}
}
@ARTICLE{Sevimli2009,
author = {Sevimli, Sevgi and Diederich, Kai and Strecker, Jan-Kolja and Schilling,
Matthias and Klocke, Rainer and Nikol, Sigrid and Kirsch, Friederike
and Schneider, Armin and Schäbitz, Wolf-Rüdiger},
title = {Endogenous brain protection by granulocyte-colony stimulating factor
after ischemic stroke},
journal = {Experimental Neurology},
year = {2009},
volume = {217},
pages = {328--335},
number = {2},
month = jun,
abstract = {Several lines of evidence have demonstrated beneficial effects of
the hematopoietic factor G-CSF in experimental stroke. A conclusive
demonstration of this effect in G-CSF deficient mice is, however,
lacking. We therefore investigated the effect of G-CSF deficiency
on infarct volumes, functional recovery, mRNA and protein expression
of the matrix metalloproteinase 9 (MMP-9) after stroke. Furthermore
we tested the efficacy of G-CSF substitution in G-CSF deficient animals
to prevent the potential consequences of G-CSF deficiency. In the
present study experimental stroke was induced in female non-treated
wildtype (wt), G-CSF deficient mice and G-CSF substituted G-CSF deficient
mice followed by assessment of infarct volumes, neurological outcome
and sensorimotor function. In addition, immunohistochemistry and
real-time PCR of the peri-ischemic area were performed. G-CSF deficient
mice showed increased infarct volumes, whereas G-CSF substituted
mice had a remarkable reduction in lesion size compared to wt mice.
These findings are accompanied by an improvement in neurological
and sensorimotor function. G-CSF deficiency resulted in an upregulation
of MMP-9 in the direct peri-ischemic tissue. Treatment with G-CSF
suppressed the upregulation of MMP-9. Taken together, G-CSF deficiency
clearly resulted in enlarged infarct volumes, and worsened neurological
outcome. G-CSF substitution abolished these negative effects, led
to significant reduced lesion volumes, and improved neurological
outcome. G-CSF mediated suppression of MMP-9 further demonstrates
that endogenous G-CSF plays a significant role in brain protective
mechanisms. We have shown for the first time that endogenous G-CSF
is required for brain recovery mechanisms after stroke.},
issn = {0014-4886},
keywords = {G-CSF, Ischemic brain injury, MMP-9, Stroke recovery},
url = {http://www.sciencedirect.com/science/article/B6WFG-4VY2CCD-1/2/8d363eaa3503089171523e14462b8090}
}
@ARTICLE{Seyfried2011,
author = {Birgit K. Seyfried and Jürgen Siekmann and Peter L. Turecek and
Hans Peter Schwarz and Friedrich Scheiflinger and Harold Zappe and
Mary L. Bossard and Günter Allmaier},
title = {PEGylated recombinant von Willebrand factor analyzed by means of
MALDI-TOF-MS, CGE-on-a-chip and nES-GEMMA},
journal = {International Journal of Mass Spectrometry},
year = {2011},
volume = {305},
pages = {157 - 163},
number = {2–3},
note = {Special Issue: In Recognition of Catherine Costello, Recipient
of the 2010 Field \& Franklin Award},
abstract = {Recombinant VWF (rVWF) is a candidate for therapy of von Willebrand
disease and the largest known multimeric glycoprotein. In this study
rVWF was covalently linked with a 20 kDa branched polyethylene
glycol (PEG) to obtain PEGylated rVWF (PEGrVWF). This conjugation
results in a further increase of heterogeneity besides glycoheterogeneity
and a challenge in analyzing of such a bioconjugate, particular when
investigated on the intact molecule level. Four different techniques
including SDS-PAGE, MALDI-TOF-MS, capillary-gel-electrophoresis-on-a-chip
(CGE-on-a-chip) and nano electrospray gas-phase electrophoretic mobility
molecular analysis (nES-GEMMA) were applied to determine the molecular
weight (MW) and the PEGylation degree of the monomeric rVWF. The
degree and distribution of PEGylation of rVWF obtained by CGE-on-a-chip
were in good agreement with results obtained by MALDI-TOF-MS with
a special high mass detector. An average PEGylation degree of 3.1
PEG chains coupled to the monomeric glycoforms was found. MW determination
by MALDI-TOF-MS (317.4 ± 1.0 kDa; 3 PEG chains attached)
showed in comparison to CGE-on-a-chip (413.4 ± 2.1 kDa)
the highest precision. Furthermore the orthogonal method, nES-GEMMA
provided first information on the globular size (11.3 ± 0.1 nm)
and based on that the MW (251 ± 7.2 kDa for the average
PEGylation) of the PEGrVWF.},
doi = {10.1016/j.ijms.2010.10.028},
issn = {1387-3806},
keywords = {Von Willebrand factor},
url = {http://www.sciencedirect.com/science/article/pii/S1387380610004094}
}
@ARTICLE{Seyoum2011,
author = {Beza Seyoum and Masahide Yano and Liise-anne Pirofski},
title = {The innate immune response to Streptococcus pneumoniae in the lung
depends on serotype and host response},
journal = {Vaccine},
year = {2011},
volume = {29},
pages = {8002 - 8011},
number = {45},
abstract = {Bacteremic pneumonia with some pneumococcal capsular serotypes, including
serotype 3 (ST3), has been associated with a higher risk of death,
whereas others, such as ST8, are associated with a lower risk. To
provide a molecular basis for understanding such differences, we
used oligo cDNA microarrays to analyze and compare the gene expression
profiles of the lungs of Balb/c mice infected intranasally with either
ST3, strain A66.1, or ST8, strain ATCC 6308 (6308). Compared to uninfected
controls, infection with either A66.1 or 6308 led to inoculum-dependent
expression of IFN-γ inducible CXC chemokines among other pro-inflammatory
genes. To investigate the role that IFN-γ inducible chemokines CXCL9,
CXCL10 and CXCL11 play in A66.1- and 6308-induced pneumonia, we examined
the effect of the absence of their common receptor, CXCR3, on intranasal
infection in CXCR3−/− (Balb/c) mice. Compared to wild type (WT)
mice, virulence of A66.1 but not 6308 was attenuated in CXCR3−/−
mice. A66.1-infected CXCR3−/− mice had fewer lung neutrophils
and more alveolar macrophages 48 h after infection and fewer
blood CFU 72 h after infection. Histopathological examination
of lung sections revealed less inflammation among A66.1-infected
CXCR3−/− than WT mice. The reduced virulence of A66.1 in CXCR3−/−
mice suggests that inhibition of the functional activity of IFN-γ
inducible chemokines modulates the host response to A66.1, in turn
suggesting a novel approach to improve vaccine-mediated protection
against ST3 pneumonia.},
doi = {10.1016/j.vaccine.2011.08.064},
issn = {0264-410X},
keywords = {Serotype 3 pneumococcus},
url = {http://www.sciencedirect.com/science/article/pii/S0264410X11013107}
}
@ARTICLE{Sfanos2008,
author = {Sfanos, Karen Sandell and Bruno, Tullia C. and Maris, Charles H.
and Xu, Lauren and Thoburn, Christopher J. and DeMarzo, Angelo M.
and Meeker, Alan K. and Isaacs, William B. and Drake, Charles G.},
title = {Phenotypic Analysis of Prostate-Infiltrating Lymphocytes Reveals
TH17 and Treg Skewing},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {3254--3261},
number = {11},
month = jun,
abstract = {Purpose: Pathologic examination of prostate glands removed from patients
with prostate cancer commonly reveals infiltrating CD4+ and CD8+
T cells. Little is known about the phenotype of these cells, despite
accumulating evidence suggesting a potential role for chronic inflammation
in the etiology of prostate cancer. Experimental Design: We developed
a technique that samples the majority of the peripheral prostate
through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes
(PIL) were isolated using magnetic beads and analyzed for subset
skewing using both flow cytometry and quantitative reverse transcription-PCR.
The transcriptional profile of fluorescence-activated cell sorted
prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was
compared with naive, peripheral blood T cells using microarray analysis.
Results: CD4+ PIL showed a paucity of TH2 (interleukin-4-secreting)
cells, a surprising finding given the generally accepted association
of these cells with chronic, smoldering inflammation. Instead, CD4+
PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+)
as well as towards the TH17 phenotype (interleukin-17+). We also
found that a preponderance of TH17-mediated inflammation was associated
with a lower pathologic Gleason score. These protein level data were
reflected at the message level, as analyzed by quantitative reverse
transcription-PCR. Microarray analysis of pooled prostate-infiltrating
Treg revealed expected Treg-associated transcripts (FoxP3, CTLA-4,
GITR, LAG-3) as well as a number of unique cell surface markers that
may serve as additional Treg markers. Conclusion: Taken together,
these data suggest that TH17 and/or Treg CD4+ T cells (rather than
TH2 T cells) may be involved in the development or progression of
prostate cancer.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/11/3254}
}
@ARTICLE{Sforza2004,
author = {Sforza, Daniel M. and Smith, Desmond J.},
title = {Voxelation Methods for Genome Scale Imaging of Brain Gene Expression},
journal = {Methods Enzymol},
year = {2004},
volume = {Volume 386},
pages = {314--323},
booktitle = {Imaging in Biological Research, Part B},
editor = {Conn, P. Michael},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B7CV2-4C9C4PY-J/2/47de28dd920b5e3ebd299437a6bd9ef8}
}
@ARTICLE{Sgarlato2005,
author = {Sgarlato, Gregory D. and Eastman, Catharine L. and Sussman, Howard
H.},
title = {Panel of Genes Transcriptionally Up-regulated in Squamous Cell Carcinoma
of the Cervix Identified by Representational Difference Analysis,
Confirmed by Macroarray, and Validated by Real-Time Quantitative
Reverse Transcription-PCR},
journal = {Clin. Chem.},
year = {2005},
volume = {51},
pages = {27--34},
number = {1},
month = jan,
abstract = {Background: The Pap smear is currently the most widely used method
of screening for squamous cell carcinoma of the cervix (SCCC). Because
it is based on cell morphology, it is subject to variability in interpretation.
Sensitive molecular markers capable of differentiating cancerous
samples from noncancerous ones would be beneficial in this regard.
Methods: We performed representational difference analysis (RDA)
using paired, noncancerous (normal) and cancerous (disease) tissues
taken from the same specimen obtained from a single patient with
a confirmed diagnosis of SCCC. Linearly amplified cDNA from normal
and diseased tissues of the original patient and seven others were
hybridized to DNA macroarrays containing the candidate gene transcript
fragments. Real-time quantitative reverse transcription-PCR was used
to validate the macroarray results. Results: RDA identified a candidate
pool of 65 transcript fragments up-regulated in diseased tissue compared
with normal tissue. Forty-one transcripts were found to be up-regulated
in diseased compared with normal tissue in at least one half the
patients by macroarray hybridization. Eleven of those genes were
selected for real-time quantitative reverse transcription-PCR analysis,
and all were confirmed as transcriptionally up-regulated in cancer
compared with normal tissue in at least one half the patients. Conclusions:
RDA using tissues from a single patient identified gene fragments
confirmed to be transcriptionally up-regulated in SCCC both in the
original patient and in seven others. The confirmed genes have a
variety of functions and also have the potential to serve as diagnostic
or prognostic markers.},
url = {http://www.clinchem.org/cgi/content/abstract/51/1/27}
}
@ARTICLE{Sgarlato2006,
author = {Sgarlato, Gregory D. and Sussman, Howard H.},
title = {Representational Fragment Amplification: Exponential Amplification
of Fragmented cDNA Enables Multimillion-Fold Expression Testing},
journal = {Clin. Chem.},
year = {2006},
volume = {52},
pages = {2164--2168},
number = {11},
month = nov,
url = {http://www.clinchem.org}
}
@ARTICLE{Sha2011a,
author = {Sha, Li and Kitchen, Rob and Porteous, David and Blackwood, Douglas
and Muir, Walter and Pickard, Benjamin},
title = {SOX11 target genes: implications for neurogenesis and neuropsychiatric
illness},
journal = {Acta Neuropsychiatrica},
year = {2011},
pages = {no--no},
abstract = {Sha L, Kitchen R, Porteous D, Blackwood D, Muir W, Pickard B. SOX11
target genes: implications for neurogenesis and neuropsychiatric
illness.Objective: Deficits in adult and embryonic neurogenesis have
been linked with neurological and psychiatric disorders, so it is
important to understand the molecular mechanisms underlying this
process. SOX11 is a transcription factor known to play a critical
role in the regulation of the neuronal and glial differentiation
stage of neurogenesis, so we hypothesised that the identification
of its target genes would reveal underlying biological processes
relevant to disease.Methods: SOX11 protein was over-expressed in
HEK293 cells and transcriptional changes assessed by microarray analysis.
Selected candidate genes were further tested for SOX11 activation
in quantitative reverse transcriptase PCR studies of HEK293 cells
and Western analysis of SH-SY5Y cells.Results: Regulated genes included
a previously established SOX11 target, known markers of neurogenesis,
as well as several genes implicated in neuropsychiatric disorders.
Immunofluorescence localised several of the genes within the proliferative
subgranular zone of the hippocampus. We observed multiple histone
and zinc finger genes regulated by SOX11, many of which were located
in two clusters on chromosomes 6 and 19. The chromosome 6 cluster
lies within a region of the genome showing the strongest genetic
association with schizophrenia.Conclusion: SOX11 appears to regulate
a complex programme of chromatin remodelling and downstream gene
expression changes to achieve a mature neuronal phenotype. SOX11
target genes are shown to be involved in neurodevelopmental processes
important in health and, potentially, disease.},
doi = {10.1111/j.1601-5215.2011.00583.x},
issn = {1601-5215},
keywords = {microarray analysis, nervous system disorders, transcription factor},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1601-5215.2011.00583.x}
}
@ARTICLE{Sha2011,
author = {Qiong Sha and Anuradha Gunathilake and Michael R.J. Forstner and
Dittmar Hahn},
title = {Temporal analyses of the distribution and diversity of Salmonella
in natural biofilms},
journal = {Systematic and Applied Microbiology},
year = {2011},
volume = {34},
pages = {353 - 359},
number = {5},
abstract = {The diversity and distribution of salmonellae in freshwater biofilms
were analyzed at a fine scale (i.e. in 20 locations from a 324 cm2
area) for two sites in San Marcos, TX. A concrete storm water overflow
channel (City Park) was sampled 4 times and a concrete surface in
the spring-fed headwaters of the San Marcos River (Spring Lake) 5
times between April and September 2009, and each biofilm sample analyzed
by a combination of traditional enrichment methods and molecular
techniques. PCR detection of the invA gene, that encodes a protein
of a type III secretion system present in salmonellae, after semi-selective
enrichment of salmonellae was achieved in biofilms from all 20 locations
at the City Park site, with locations generally being positive 2–3
times out of 4 sampling times for a total of 59% positive samples.
InvA gene fragment detection in biofilms was less frequent for the
5 sampling times and 20 locations from the Spring Lake site (18%
of all samples), with 1 sampling time being entirely negative and
8 locations remaining negative throughout the study. Rep-PCR fingerprinting
of 491 Salmonella isolates obtained from both sites resulted in 30
distinct profiles, with 26 and 7 profiles retrieved from City Park
and Spring Lake samples, respectively, and thus with 3 profiles present
at both sites, and multiple strains frequently obtained from single
locations at both sites. The composition of Salmonella strains in
the area analyzed changed in time with large differences between
early (April, June) and late sampling times (September) within and
among sites, except for one strain (S12) that was present at almost
all sampling times at both sites, though often at different locations
within the area analyzed. These results demonstrate the presence
of salmonellae in natural biofilms and a significant micro-heterogeneity
with differences in diversity and persistence of salmonellae.},
doi = {10.1016/j.syapm.2011.01.005},
issn = {0723-2020},
keywords = {Biofilms},
url = {http://www.sciencedirect.com/science/article/pii/S0723202011000786}
}
@ARTICLE{Shabala2009,
author = {Shabala, Lana and Bowman, John and Brown, Janelle and Ross, Tom and
McMeekin, Tom and Shabala, Sergey},
title = {Ion transport and osmotic adjustment in Escherichia coli in response
to ionic and non-ionic osmotica},
journal = {Environmental Microbiology},
year = {2009},
volume = {11},
pages = {137--148},
number = {1},
abstract = {Summary Bacteria respond to osmotic stress by a substantial increase
in the intracellular osmolality, adjusting their cell turgor for
altered growth conditions. Using Escherichia coli as a model organism
we demonstrate here that bacterial responses to hyperosmotic stress
specifically depend on the nature of osmoticum used. We show that
increasing acute hyperosmotic NaCl stress above ∼1.0 Os kg−1
causes a dose-dependent K+ leak from the cell, resulting in a substantial
decrease in cytosolic K+ content and a concurrent accumulation of
Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment
(non-ionic osmotica) results in a gradual increase of the net K+
uptake. Ion flux data are consistent with growth experiments showing
that bacterial growth is impaired by NaCl at the concentration resulting
in a switch from net K+ uptake to efflux. Microarray experiments
reveal that about 40% of upregulated genes shared no similarity in
their responses to NaCl and sucrose treatment, further suggesting
specificity of osmotic adjustment in E. coli to ionic and non-ionic
osmotica. The observed differences are explained by the specificity
of the stress-induced changes in the membrane potential of bacterial
cells highlighting the importance of voltage-gated K+ transporters
for bacterial adaptation to hyperosmotic stress.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2008.01748.x}
}
@ARTICLE{Shacklett2004,
author = {Shacklett, Barbara L. and Cox, Catherine A. and Quigley, Maire F.
and Kreis, Christophe and Stollman, Neil H. and Jacobson, Mark A.
and Andersson, Jan and Sandberg, Johan K. and Nixon, Douglas F.},
title = {Abundant Expression of Granzyme A, but Not Perforin, in Granules
of CD8+ T Cells in GALT: Implications for Immune Control of HIV-1
Infection},
journal = {J. Immunol.},
year = {2004},
volume = {173},
pages = {641--648},
number = {1},
month = jul,
abstract = {Because GALT is a major portal of entry for HIV-1 and reservoir for
viral replication, we hypothesized that an ineffective cellular immune
response in intestinal mucosa might partially explain the failure
of immune control in AIDS. In this study, we demonstrate that the
vast majority of CD8+ T cells in rectal tissue, including HIV-1-specific
cells, fail to express the cytolytic protein, perforin. However,
rectal CD8+ T cells do express granzyme A, and are also capable of
releasing IFN-{gamma} upon stimulation with cognate peptide. Confocal
microscopy showed that granzyme A was located in intracellular granules
in the absence of perforin. The majority of rectal CD8+ T cells exhibit
an effector memory phenotype, expressing CD45RO but not CCR7. Quantitative
real-time PCR analysis demonstrated that perforin RNA is expressed
in rectal CD8+ T cells from healthy and HIV-1-positive individuals.
In HIV-1-positive individuals, similar amounts of perforin RNA were
detected in CD8+ T cells from rectal tissue and PBMC, despite a relative
absence of perforin protein in rectal tissue. These findings demonstrate
an important difference in perforin expression between CD8+ T cells
in blood and mucosa. Furthermore, the relative absence of armed effector
cells may serve to protect the integrity of rectal mucosa under normal
conditions, but might also provide an early advantage to HIV-1 and
other sexually transmitted viruses.},
url = {http://www.jimmunol.org/cgi/content/abstract/173/1/641}
}
@ARTICLE{Shah2004,
author = {Shah, Gaurang and Azizian, Maria and Bruch, David and Mehta, Rajil
and Kittur, Dilip},
title = {Cross-species comparison of gene expression between human and porcine
tissue, using single microarray platform – preliminary results},
journal = {Clinical Transplantation},
year = {2004},
volume = {18},
pages = {76--80},
abstract = {Abstract:  Introduction:  Xenotransplantation is a potential solution
for inadequate supply of donor organs. Pigs are considered the ideal
donor for kidney transplantation to human recipients, therefore it
is important to understand the gene regulation in the porcine organs.
Oligonucleotide array technology has been utilized largely for human,
mouse and rat gene expression studies only. Its use with porcine
genes has not been reported. We investigated the possibility of studying
gene regulation in porcine kidney with a human GeneChip microarray®
platform. Methods:  To assess the feasibility of using a single
microarrray platform for comparison of expressing data across different
species (human and pig), we compared the gene expression profiles
of human brain, human kidney and pig kidney using the Affymetrix
U-133 A human GeneChip®, which contains probes for 22 283 genes.
Kidney biopsies from pigs and humans, with normal histology, were
used to obtain RNA for porcine and human samples, while a commercially
available adult whole cortex total RNA sample (Clontech) was used
for the human sample. We assessed the intensity ratio for housekeeping
and tissue specific genes. To examine the potential for non-specific
binding to create false positive errors in our data, we compared
the expression profiles in our experiments to a number of public
databases. Results:  There were approximately the same number of
genes expressed at higher levels in the pig kidney as in the human
kidney and human brain. The major differences in gene expression
were found for genes with tissue specific patterns of expression.
Eighty genes were increased in human brain vs. human and pig kidney
samples. Two hundred and eighty genes were increased in human and
pig kidney vs. human brain samples. Of the top 25 genes increased
in pig kidney compared with human brain, we were able to cross-reference
18 genes to the Unigene and SAGE public databases. We confirmed the
expected higher levels of expression in the kidney in 18 genes. Of
the top 25 genes increased in human brain vs. pig kidney, we were
able to cross-reference 20 genes to the Unigene and SAGE databases
and confirm the expected higher expression levels in brain in 17
genes with three inconclusive genes. Conclusion:  This low level
of false positive findings, at this preliminary stage, supports the
concept of using human GeneChip® microarray platform to compare
gene expression profiles between pig and human tissues in the absence
of a porcine microarray platform. Our study opens a new avenue into
the analysis of porcine genes relevant to xenotransplantation.},
issn = {1399-0012},
keywords = {cross-species, gene expression, microarray},
publisher = {Blackwell Publishers},
url = {http://dx.doi.org/10.1111/j.1399-0012.2004.00223.x}
}
@ARTICLE{Shah2008,
author = {Shah, Gaurang and Middleton, Frank A. and Gentile, Karen L. and Tripathi,
Sudipta and Bruch, David and Maier, Kristopher G. and Kittur, Dilip
S.},
title = {Cyclosporine Inhibition of Angiogenesis Involves the Transcription
Factor HESR1},
journal = {Journal of Surgical Research},
year = {2008},
volume = {149},
pages = {171--176},
number = {2},
month = oct,
abstract = {Purpose Angiogenesis is critical in normal development and in tumor
growth. Experimentally, cyclosporine A (CyA) inhibits angiogenesis
in an in vivo mouse model and an in vitro capillary tube model. The
mechanisms behind its antiangiogenic effects are not well characterized.
To determine which nuclear factor, if any, may be involved in the
antiangiogenic effects of CyA, we performed a microarray analysis
of human aortic endothelial cells (HAEC) subjected to CyA and another
calcineurin inhibitor, FK 506.Methods HAEC were divided into four
groups: (1) HAEC incubated with CyA 2 [mu]g/mL; (2) HAEC incubated
with CyA 10 [mu]g/mL; (3) HAEC incubated with FK 506 1 [mu]g/mLl
for 24 h; and (4) HAEC as control. We used Affymetrix GeneChip U133-A
for gene expression analysis and validated our results with quantitative
reverse transcription-polymerase chain reaction.Results At a 2 [mu]g/mL
dose, CyA treated HAEC revealed a 44-fold increase in the expression
of hairy enhancer of split-related protein 1 (HESR1) and 1.73-fold
down-regulation of transcripts encoding for the vascular endothelial
growth factor (VEGF) receptor (VEGFR2). At 10 [mu]g/mL, the expression
of the HESR1 transcript was 57-fold higher than control, and VEGFR2
exhibited a 1.93-fold down-regulation. Quantitative reverse transcription-polymerase
chain reaction confirmed a significant (P < 0.0001) increase in expression
of HESR1 in CyA treated cells. In contrast, the expression level
of HESR1 was not affected by the FK 506 treatment.Conclusion CyA
demonstrate antiangiogenic activities linked to an overexpression
of HESR1 transcription factor, and down-regulation of VEGFR2. Thus,
use of high-dose CyA may provide a novel treatment in angiogenesis
dependent disease.},
issn = {0022-4804},
keywords = {angiogenesis, cyclosporine A, HESR1, HEY1, VEGFR2},
url = {http://www.sciencedirect.com/science/article/B6WM6-4S7RR7G-3/2/9058547e3db55244fc3d7531501485bc}
}
@ARTICLE{Shah2010,
author = {Shah, G. D. and Socci, N. D. and Gold, J. S. and Wolchok, J. D. and
Carvajal, R. D. and Panageas, K. S. and Viale, A. and Brady, M. S.
and Coit, D. G. and Chapman, P. B.},
title = {Phase II trial of neoadjuvant temozolomide in resectable melanoma
patients},
journal = {Annals of Oncology},
year = {2010},
volume = {21},
pages = {1718--1722},
number = {8},
month = aug,
abstract = {Background: We treated melanoma patients with temozolomide (TMZ) in
the neoadjuvant setting and collected cryopreserved tumor samples
before and after treatment. The primary objective was to determine
whether the response proportion was higher than previously reported
in widely metastatic patients. A secondary objective was to test
the feasibility of obtaining adequate tissue before and after treatment
for genetic testing.Materials and methods: Chemotherapy-naive melanoma
patients who were candidates for surgical resection were eligible.
TMZ was administered orally at 75 mg/m2/day for 6 weeks of every
8-week cycle. Cycles were repeated until complete response (CR),
progression, or stable disease (SD) for two cycles.Results: Of 19
assessable patients, 2 had CRs and 1 had partial response. Four patients
had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase
(MGMT) promoter was unmethylated in all nine patients analyzed including
from the two CR patients. Pretreatment tumor microarray results were
obtained in 16 of 19 patients.Conclusions: The response proportion
to TMZ in the neoadjuvant setting was 16%, not different than in
the metastatic setting. Responses were seen even in tumors with a
methylated MGMT promoter. Pretreatment cryopreserved tumor adequate
for microarray analysis could be obtained in most, but not all, patients.
Post-treatment tumor was unavailable in complete responders.},
url = {http://annonc.oxfordjournals.org/content/21/8/1718.abstract}
}
@ARTICLE{Shah2009,
author = {Shah, Girish V. and Muralidharan, Anbalagan and Gokulgandhi, Mitan
and Soan, Kamal and Thomas, Shibu},
title = {Cadherin Switching and Activation of {beta}-Catenin Signaling Underlie
Proinvasive Actions of Calcitonin-Calcitonin Receptor Axis in Prostate
Cancer},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {1018--1030},
number = {2},
month = jan,
abstract = {Calcitonin, a neuroendocrine peptide, and its receptor are localized
in the basal epithelium of benign prostate but in the secretory epithelium
of malignant prostates. The abundance of calcitonin and calcitonin
receptor mRNA displays positive correlation with the Gleason grade
of primary prostate cancers. Moreover, calcitonin increases tumorigenicity
and invasiveness of multiple prostate cancer cell lines by cyclic
AMP-dependent protein kinase-mediated actions. These actions include
increased secretion of matrix metalloproteinases and urokinase-type
plasminogen activator and an increase in prostate cancer cell invasion.
Activation of calcitonin-calcitonin receptor autocrine loop in prostate
cancer cell lines led to the loss of cell-cell adhesion, destabilization
of tight and adherens junctions, and internalization of key integral
membrane proteins. In addition, the activation of calcitonin-calcitonin
receptor axis induced epithelial-mesenchymal transition of prostate
cancer cells as characterized by cadherin switch and the expression
of the mesenchymal marker, vimentin. The activated calcitonin receptor
phosphorylated glycogen synthase kinase-3, a key regulator of cytosolic
{beta}-catenin degradation within the WNT signaling pathway. This
resulted in the accumulation of intracellular {beta}-catenin, its
translocation in the nucleus, and transactivation of {beta}-catenin-responsive
genes. These results for the first time identify actions of calcitonin-calcitonin
receptor axis on prostate cancer cells that lead to the destabilization
of cell-cell junctions, epithelial-to-mesenchymal transition, and
activation of WNT/{beta}-catenin signaling. The results also suggest
that cyclic AMP-dependent protein kinase plays a key role in calcitonin
receptor-induced destabilization of cell-cell junctions and activation
of WNT-{beta}-catenin signaling.},
url = {http://www.jbc.org/cgi/content/abstract/284/2/1018}
}
@ARTICLE{Shah2008a,
author = {Shah, Girish V and Thomas, Shibu and Muralidharan, Anbalagan and
Liu, Yong and Hermonat, Paul L and Williams, Jill and Chaudhary,
Jaideep},
title = {Calcitonin promotes in vivo metastasis of prostate cancer cells by
altering cell signaling, adhesion, and inflammatory pathways},
journal = {Endocr. Relat. Cancer},
year = {2008},
volume = {15},
pages = {953--964},
number = {4},
month = dec,
abstract = {Expression of calcitonin (CT) and its receptor (CTR) is elevated in
advanced prostate cancer (PC). Although the significance of CT-CTR
axis in PC cell growth, invasion, and epithelial to mesenchymal transition
has been established, its role in tumor metastasis has not been examined.
To examine the role of CT-CTR axis in tumor metastasis, we employed
stable CT-CTR activated and silenced system of three PC cell lines,
LNCaP cells that lack endogenous CT, PC-3 cells that lack endogenous
CTR, and PC-3M cells that co-express CT and CTR. Enforced expression
of CT in LNCaP cells and CTR in PC-3 cells increased their ability
to form orthotopic tumors and distant metastases in multiple organs.
By contrast, silencing of CT expression in PC-3M cells not only reduced
their tumorigenicity, but also completely abrogated their metastatic
potential. To investigate the effect of in vivo silencing of CT expression
on tumor growth, we employed recombinant adeno-associated virus (rAAV)
to deliver anti-CT ribozymes in preexisting tumors of nude mice and
large probasin promoter (LPB)-Tag transgenic mice. rAAV-CT- treatment
not only abrogated the growth of pre-implanted tumors in nude mice,
but also significantly reduced the growth of spontaneous tumors in
LPB-Tag mice. Analysis of CT upregulated and silenced PC-3M transcriptomes
revealed 105 genes affected by the modulation of CT expression. These
CT signature genes generated survival, adhesion, pro-inflammatory,
and pro-metastatic pathways. Added together, these data indicate
a pivotal role for CT-CTR axis in PC metastasis and may serve as
a potential therapeutic target for advanced PC.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/15/4/953}
}
@ARTICLE{Shah2011,
author = {Shah, Manish A. and Khanin, Raya and Tang, Laura and Janjigian, Yelena
Y. and Klimstra, David S. and Gerdes, Hans and Kelsen, David P.},
title = {Molecular Classification of Gastric Cancer: A New Paradigm},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {2693--2701},
number = {9},
month = may,
abstract = {Purpose: Gastric cancer may be subdivided into 3 distinct subtypes--proximal,
diffuse, and distal gastric cancer--based on histopathologic and
anatomic criteria. Each subtype is associated with unique epidemiology.
Our aim is to test the hypothesis that these distinct gastric cancer
subtypes may also be distinguished by gene expression analysis. Experimental
Design: Patients with localized gastric adenocarcinoma being screened
for a phase II preoperative clinical trial (National Cancer Institute,
NCI #5917) underwent endoscopic biopsy for fresh tumor procurement.
Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection
was carried out to ensure more than 80% carcinoma in the sample.
HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis,
and all arrays were processed and analyzed using the Bioconductor
R-package. Results: Between November 2003 and January 2006, 57 patients
were screened to identify 36 patients with localized gastric cancer
who had adequate RNA for expression analysis. Using supervised analysis,
we built a classifier to distinguish the 3 gastric cancer subtypes,
successfully classifying each into tightly grouped clusters. Leave-one-out
cross-validation error was 0.14, suggesting that more than 85% of
samples were classified correctly. Gene set analysis with the false
discovery rate set at 0.25 identified several pathways that were
differentially regulated when comparing each gastric cancer subtype
to adjacent normal stomach. Conclusions: Subtypes of gastric cancer
that have epidemiologic and histologic distinctions are also distinguished
by gene expression data. These preliminary data suggest a new classification
of gastric cancer with implications for improving our understanding
of disease biology and identification of unique molecular drivers
for each gastric cancer subtype. Clin Cancer Res; 17(9); 2693-701.
(C)2011 AACR.},
comment = {10.1158/1078-0432.CCR-10-2203},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/9/2693}
}
@ARTICLE{Shah2009a,
author = {Shah, S.M. and Kang, Y.-J. and Christensen, B.L. and Feng, A.S. and
Kollmar, R.},
title = {Expression of Wnt receptors in adult spiral ganglion neurons: frizzled
9 localization at growth cones of regenerating neurites},
journal = {Neuroscience},
year = {2009},
volume = {164},
pages = {478--487},
number = {2},
month = dec,
abstract = {Little is known about signaling pathways, besides those of neurotrophic
factors, that are operational in adult spiral ganglion neurons. In
patients with sensorineural hearing loss, such pathways could eventually
be targeted to stimulate and guide neurite outgrowth from the remnants
of the spiral ganglion towards a cochlear implant, thereby improving
the fidelity of sound transmission. To systematically identify neuronal
receptors for guidance cues in the adult cochlea, we conducted a
genome-wide cDNA microarray screen with 2-month-old CBA/CaJ mice.
A meta-analysis of our data and those from older mice in two other
studies revealed the presence of neuronal transmembrane receptors
that represent all four established guidance pathways--ephrin, netrin,
semaphorin, and slit--in the mature cochlea as late as 15 months.
In addition, we observed the expression of all known receptors for
the "wingless-related MMTV integration site" (Wnt) morphogens, whose
neuronal guidance function has only recently been recognized. In
situ hybridizations located the mRNAs of the Wnt receptors frizzled
1, 4, 6, 9, and 10 specifically in adult spiral ganglion neurons.
Finally, frizzled 9 protein was found in the growth cones of adult
spiral ganglion neurons that were regenerating neurites in culture.
We conclude from our results that adult spiral ganglion neurons are
poised to respond to neurite damage, owing to the constitutive expression
of a large and diverse collection of guidance receptors. Wnt signaling,
in particular, emerges as a candidate pathway for guiding neurite
outgrowth towards a cochlear implant after sensorineural hearing
loss.},
issn = {0306-4522},
keywords = {cell surface receptors, cochlea, in situ hybridization, mice, microarray
analysis},
url = {http://www.sciencedirect.com/science/article/B6T0F-4X3N460-4/2/cc036ed9fc59eba5df4fd9417f9bcf9c}
}
@ARTICLE{Shahryarinejad2010,
author = {Shahryarinejad, Azin and Gardner, Thomas R. and Cline, J. Mark and
Levine, William N. and Bunting, Haley A. and Brodman, Michael D.
and Ascher-Walsh, Charles J. and Scotti, Richard J. and Vardy, Michael
D.},
title = {Effect of hormone replacement and selective estrogen receptor modulators
(SERMs) on the biomechanics and biochemistry of pelvic support ligaments
in the cynomolgus monkey (Macaca fascicularis)},
journal = {Am J Obstet Gynecol},
year = {2010},
volume = {202},
pages = {485.e1--485.e9},
number = {5},
month = may,
abstract = {To evaluate the effect of selective estrogen receptor modulators and
ethinyl estradiol on the biomechanical and biochemical properties
of the uterosacral and round ligaments in the monkey model of menopause.
A randomized, double-blind, placebo-controlled study on 11 female
macaque monkeys. Ovariectomized monkeys received 12 weeks of placebo,
raloxifene, tamoxifen, or ethinyl estradiol. Biomechanical step-strain
testing and real-time polymerase chain reaction was performed on
the uterosacral and round ligaments. Tamoxifen and raloxifene uterosacrals
expressed differing collagen I /III receptor density ratios, but
both selective estrogen receptor modulators showed decreased tensile
stiffness compared to ethinyl estradiol and controls. These findings
support a possible effect of selective estrogen receptor modulators
on biomechanical and biochemical properties of uterosacrals. This
may play a role in pelvic organ prolapse.},
issn = {0002-9378},
keywords = {macaca fascicularis, pelvic organ prolapse, round ligament, SERMs,
uterosacral ligament},
publisher = {Elsevier,},
refid = {S0002-9378(10)00104-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0002937810001043?showall=true}
}
@ARTICLE{Shajahan2007,
author = {Shajahan, Ayesha N. and Wang, Aifen and Decker, Markus and Minshall,
Richard D. and Liu, Minetta C. and Clarke, Robert},
title = {Caveolin-1 Tyrosine Phosphorylation Enhances Paclitaxel-mediated
Cytotoxicity},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {5934--5943},
number = {8},
month = feb,
abstract = {Caveolin-1 (CAV1), a highly conserved membrane-associated protein,
is a putative regulator of cellular transformation. CAV1 is localized
in the plasmalemma, secretory vesicles, Golgi, mitochondria, and
endoplasmic reticulum membrane and associates with the microtubule
cytoskeleton. Taxanes such as paclitaxel (Taxol) are potent anti-tumor
agents that repress the dynamic instability of microtubules and arrest
cells in the G2/M phase. Src phosphorylation of Tyr-14 on CAV1 regulates
its cellular localization and function. We report that phosphorylation
of CAV1 on Tyr-14 regulates paclitaxel-mediated apoptosis in MCF-7
breast cancer cells. Befitting its role as a multitasking molecule,
we show that CAV1 sensitizes cells to apoptosis by regulating cell
cycle progression and activation of the apoptotic signaling molecules
BCL2, p53, and p21. We demonstrate that phosphorylated CAV1 triggers
apoptosis by inactivating BCL2 and increasing mitochondrial permeability
more efficiently than non-phosphorylated CAV1. Furthermore, expression
of p21, which correlates with taxane sensitivity, is regulated by
CAV1 phosphorylation in a p53-dependent manner. Collectively, our
findings underscore the importance of CAV1 phosphorylation in apoptosis
and suggest that events that negate CAV1 tyrosine phosphorylation
may contribute to anti-microtubule drug resistance.},
url = {http://www.jbc.org/cgi/content/abstract/282/8/5934}
}
@ARTICLE{Shan2008,
author = {Shan, Jinyu and Jia, Ying and Clokie, Martha R.J. and Mann, Nicholas
H.},
title = {Infection by the ‘photosynthetic’ phage S-PM2 induces increased
synthesis of phycoerythrin in Synechococcus sp. WH7803},
journal = {FEMS Microbiology Letters},
year = {2008},
volume = {283},
pages = {154--161},
number = {2},
abstract = {Abstract Phycoerythrin-containing Synechococcus strains are unicellular
cyanobacteria that are of great ecological importance in the marine
environment. These organisms are known to be susceptible to infection
by cyanophages (viruses that infect cyanobacteria). The infection
cycle takes several hours and during this time the cyanophages may
potentially modify the cyanobacterial light-harvesting apparatus.
This study based on a model system consisting of Synechococcus sp.
WH7803 and cyanophage S-PM2 revealed a progressive increase in the
content of phycoerythrin per cell and per phycobilisome postinfection
using absorption and emission spectrophotometry and sodium dodecyl
sulphate-polyacrylamide gel electrophoresis. An increased cellular
content of chlorophyll a was also revealed using absorption spectrophotometry.
The transcript levels of the phycoerythrin-coding operons, mpeBA
and cpeBA, were found to increase after phage infection using quantitative
real-time PCR. This phage-induced increase in light-harvesting capacity
could potentially increase the photosynthetic activity of the host
to satisfy the phage's energy demand for reproduction.},
issn = {1574-6968},
keywords = {Synechococcus, cyanophage, phycobilisome, phycoerythrin, marine, phage},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2008.01148.x}
}
@ARTICLE{Shan2010,
author = {Shan, Jixiu and Lopez, Maria-Cecilia and Baker, Henry V. and Kilberg,
Michael S.},
title = {Expression profiling after activation of amino acid deprivation response
in HepG2 human hepatoma cells},
journal = {Physiol Genomics},
year = {2010},
volume = {41},
pages = {315--327},
number = {3},
month = may,
abstract = {Dietary protein malnutrition is manifested as amino acid deprivation
of individual cells, which activates an amino acid response (AAR)
that alters cellular functions, in part, by regulating transcriptional
and posttranscriptional mechanisms. The AAR was activated in HepG2
human hepatoma cells, and the changes in mRNA content were analyzed
by microarray expression profiling. The results documented that 1,507
genes were differentially regulated by P < 0.001 and by more than
twofold in response to the AAR, 250 downregulated and 1,257 upregulated.
The spectrum of altered genes reveals that amino acid deprivation
has far-reaching implications for gene expression and cellular function.
Among those cellular functions with the largest numbers of altered
genes were cell growth and proliferation, cell cycle, gene expression,
cell death, and development. Potential biological relationships between
the differentially expressed genes were analyzed by computer software
that generates gene networks. Proteins that were central to the most
significant of these networks included c-myc, polycomb group proteins,
transforming growth factor {beta}1, nuclear factor (erythroid-derived
2)-like 2-related factor 2, FOS/JUN family members, and many members
of the basic leucine zipper superfamily of transcription factors.
Although most of these networks contained some genes that were known
to be amino acid responsive, many new relationships were identified
that underscored the broad impact that amino acid stress has on cellular
function.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/41/3/315}
}
@ARTICLE{Shang2012,
author = {Shang, Fengjun and Guihen, Elizabeth and Glennon, Jeremy D.},
title = {Recent advances in miniaturisation – The role of microchip electrophoresis
in clinical analysis},
journal = {ELECTROPHORESIS},
year = {2012},
volume = {33},
pages = {105--116},
number = {1},
abstract = {This review aims to highlight the current role of microchip CE (MCE)
in clinical analysis to date, and also its future potential in this
important area. One of the most notable advancements in separation
science, which has accelerated in the last decade, has been the use
of plastic and glass microchips to achieve high-speed electrophoresis
separations in seconds, requiring only pico or nanolitre sample volumes.
So far, in the clinical laboratory, MCE has lent itself to the resolution
of very complex challenging analytes such as DNA, RNA, protein analysis,
cellular components and other disease biomarkers. At present, most
basic clinical laboratories rely heavily upon various kinds of enzymatic
immunoassays as these methods offer speed, specificity, reliability
and are well established analytical methods. However, this is not
always the case, as with all analytical methods there are limitations,
and sometimes enzymatic-based assays can be challenged by low-level
concentration of target analytes present in samples resulting in
high RSD values and results that cannot be interpreted. In some cases,
this difficulty can be exasperated when complex sample matrices are
presented for analysis, and interfering components result in highly
exaggerated results from unwanted extra enzymatic binding. MCE may
have a role in providing alternative highly sophisticated automated
clinical analysis using state-of-the-art methodologies.},
doi = {10.1002/elps.201100454},
issn = {1522-2683},
keywords = {Clinical analysis, Microchip capillary electrophoresis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.201100454}
}
@ARTICLE{Shang2006,
author = {Shang, X.Z. and Ma, K.Y. and Radewonuk, J. and Li, J. and Song, X.Y.
and Griswold, D.E. and Emmell, E. and Li, L.},
title = {IgE isotype switch and IgE production are enhanced in IL-21-deficient
but not IFN-[gamma]-deficient mice in a Th2-biased response},
journal = {Cellular Immunology},
year = {2006},
volume = {241},
pages = {66--74},
number = {2},
month = jun,
abstract = {IgE plays a critical role in the pathogenesis of allergy and asthma.
Therefore, suppression of IgE production would provide therapeutic
benefits to patients suffering from these diseases. We have reported
that the production of IgE is regulated differently in the spleen
vs. the draining lymph nodes (LN). IgE isotype switch and IgE producing
B cell expansion occur in the draining LN after antigen (Ag) immunization,
but do not happen in the spleen. In addition, a population of pre-existing
IgE+ cells is observed in the spleen of normal or sham immunized
mice, but is not present in the draining LN. To further understand
the regulation of IgE production in different lymphoid organs, and
the potential inhibitory factors of IgE isotype switch in the spleen,
the involvement of IL-21 and IFN-[gamma] in regulating IgE production
was investigated by using the IL-21 and the IFN-[gamma] deficient
mice. We found that in the absence of IL-21 IgE isotype switch and
IgE+ cell clonal expansion were dramatically enhanced in the spleen
and IgE isotype switch was partially increased in the draining LN.
In addition, IgE production of the pre-existing CD19-CD5+B220low
IgE+ cells in the spleen was also increased in the absence of IL-21
under physiological conditions. In contrast, using the IFN-[gamma]
deficient mice, we did not observe a negative impact of IFN-[gamma]
on either IgE isotype switch or IgE production. Our data suggest
that IL-21 appears to be a critical cytokine to keep low IgE levels
under physiological and pathological conditions.},
issn = {0008-8749},
keywords = {IgE, IL-21, IFN-[gamma], Th2},
url = {http://www.sciencedirect.com/science/article/B6WCF-4KXDWMG-1/2/c7704a2cad8d7f1dd26920b3fd8f4a0e}
}
@ARTICLE{Shankar2006,
author = {Shankar, Kartik and Hidestrand, Mats and Haley, Rani and Skinner,
Robert A. and Hogue, William and Jo, Chan-Hee and Simpson, Pippa
and Lumpkin, Charles K., Jr. and Aronson, James and Badger, Thomas
M. and Ronis, Martin J. J.},
title = {Different Molecular Mechanisms Underlie Ethanol-Induced Bone Loss
in Cycling and Pregnant Rats},
journal = {Endocrinology},
year = {2006},
volume = {147},
pages = {166--178},
number = {1},
month = jan,
abstract = {Chronic ethanol (EtOH) consumption can result in osteopenia. In the
current study, we examined the modulation of EtOH-induced bone loss
during pregnancy. Nonpregnant and pregnant dams were intragastrically
infused either control or EtOH-containing diets throughout gestation
(gestation d 5 through 20 or an equivalent period of 15 d) by total
enteral nutrition. The effects of EtOH (8.5 to 14 g/kg/d) on tibial
bone mineral density (BMD), mineral content (BMC), and bone mineral
area were assessed at gestation d 20 via peripheral quantitative
computerized tomography. EtOH caused a dose-dependent decrease in
BMD and BMC without affecting bone mineral area. Trabecular BMD and
BMC were significantly lower in EtOH-treated, nonpregnant dams, compared
with pregnant cohorts at the same infused dose of EtOH and urinary
ethanol concentrations. Static histomorphometric analysis of tibiae
from pregnant rats after EtOH treatment showed decreased osteoblast
and osteoid surface, indicating inhibited bone formation, whereas
EtOH-treated cycling rats showed higher osteoclast and eroded surface,
indicative of increased bone resorption. Circulating osteocalcin
and 1,25-dihydroxyvitamin D3 were lower in both EtOH-fed nonpregnant
and pregnant rats. Gene expression of osteoclast markers, 70 kDa
v-ATPase, and tartrate-resistant acid phosphatase were increased
selectively in nonpregnant EtOH-treated rats but not pregnant rats.
Moreover, only nonpregnant EtOH-fed rats showed induction in bone
marrow receptor activator of nuclear factor-{kappa}B ligand mRNA
and decreased circulating 17{beta}-estradiol levels. Our data suggest
that EtOH-induced bone loss in pregnant rats is mainly due to inhibited
bone formation, whereas in nonpregnant rats, the data are consistent
with increased osteoclast activation and bone resorption concomitant
with decreased estradiol levels.},
url = {http://endo.endojournals.org/cgi/content/abstract/147/1/166}
}
@ARTICLE{Shankar2006a,
author = {Shankar, Kartik and Hidestrand, Mats and Liu, Xiaoli and Xiao, Rijin
and Skinner, Charles M. and Simmen, Frank A. and Badger, Thomas M.
and Ronis, Martin J. J.},
title = {Physiologic and Genomic Analyses of Nutrition-Ethanol Interactions
During Gestation: Implications for Fetal Ethanol Toxicity},
journal = {Exp Biol Med},
year = {2006},
volume = {231},
pages = {1379--1397},
number = {8},
month = sep,
abstract = {Nutrition-ethanol (EtOH) interactions during gestation remain unclear
primarily due to the lack of appropriate rodent models. In the present
report we utilize total enteral nutrition (TEN) to specifically understand
the roles of nutrition and caloric intake in EtOH-induced fetal toxicity.
Time-impregnated rats were intragastrically fed either control or
diets containing EtOH (8-14 g/kg/day) at a recommended caloric intake
for pregnant rats or rats 30% undernourished, from gestation day
(GD) 6-20. Decreased fetal weight and litter size (P < 0.05) and
increased full litter resorptions (33% vs. 0%), were observed in
undernourished dams compared to adequately fed rats given the same
dose of EtOH, while undernutrition alone did not produce any fetal
toxicity. Undernutrition led to impairment of EtOH metabolism, increased
blood EtOH concentrations (160%), and decreased maternal hepatic
ADH1 mRNA, protein, and activity. Microarray analyses of maternal
hepatic gene expression on GD15 revealed that 369 genes were altered
by EtOH in the presence of undernutrition, as compared to only 37
genes by EtOH per se ({+/-}2-fold, P < 0.05). Hierarchical clustering
and gene ontology analysis revealed that stress and external stimulus
responses, transcriptional regulation, cellular homeostasis, and
protein metabolism were affected uniquely in the EtOH-under-nutrition
group, but not by EtOH alone. Microarray data were confirmed using
real-time RT-PCR. Undernourished EtOH-fed animals had 2-fold lower
IGF-1 mRNA and 10-fold lower serum IGF-1 protein levels compared
to undernourished controls (P < 0.0005). Examination of maternal
GH signaling via STAT5a and -5b revealed significant reduction in
both gene and protein expression produced by both EtOH and undernutrition.
However, despite significantly elevated fetal BECs, fetal IGF-1 mRNA
and protein were not affected by EtOH or EtOH-undernutrition combinations.
Our data suggest that undernutrition potentiates the fetal toxicity
of EtOH in part by disrupting maternal GH-IGF-1, signaling thereby
decreasing maternal uterine capacity and placental growth.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/231/8/1379}
}
@ARTICLE{Shankar2008,
author = {Shankar, Kartik and Liu, Xiaoli and Singhal, Rohit and Chen, Jin-Ran
and Nagarajan, Shanmugam and Badger, Thomas M. and Ronis, Martin
J. J.},
title = {Chronic Ethanol Consumption Leads to Disruption of Vitamin D3 Homeostasis
Associated with Induction of Renal 1,25 Dihydroxyvitamin D3-24-Hydroxylase
(CYP24A1)},
journal = {Endocrinology},
year = {2008},
volume = {149},
pages = {1748--1756},
number = {4},
month = apr,
abstract = {Bone loss resulting from chronic ethanol (EtOH) abuse is frequently
accompanied by altered vitamin D3 homeostasis. In the current study,
we examined EtOH effects in a female rat model in which control or
EtOH-containing diets were infused intragastrically. EtOH treatment
reduced plasma 1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) coincident
with a decrease in renal CYP27B1 (25(OH)D3 1{alpha}-hydroxylase)
mRNA and an increase in expression of renal CYP24A1 (1,25 (OH)2 D3-
24-hydroxylase). EtOH induction of CYP24A1 occurred as a result of
increased transcription and was also observed in vitro in primary
cultures of rat renal proximal tubule cells (RPTCs) and in NRK-52E
cells. Synergistic induction of CYP24A1 by EtOH in combination with
1,25 (OH)2 D3 was observed. The major EtOH metabolizing enzymes,
alcohol dehydrogenase-1 and CYP2E1, were induced by EtOH in RPTCs.
Inhibition of EtOH metabolism by 4-methylpyrazole inhibited the induction
of CYP24A1 mRNA. CYP24A1 mRNA induction in RPTCs was also inhibited
by the protein synthesis inhibitor cycloheximide. CYP24A1 was also
induced after hydrogen peroxide treatment, and EtOH treatment of
RPTCs resulted in production of reactive oxygen species as measured
by flow cytometry using the fluorescent probe dichlorofluorescin
acetate. In addition, inhibition of MAPK signaling pathways with
the MAPK kinase inhibitor U0126 or the p38 inhibitor SB203580 inhibited
EtOH induction of CYP24A1. Our data suggest that EtOH reduces circulating
1,25 (OH)2 D3 concentrations as the result of CYP24A1 induction that
is mediated via MAPK activation resulting from renal oxidative stress
produced by local metabolism of EtOH via CYP2E1 and antidiuretic
hormone-1.},
url = {http://endo.endojournals.org/cgi/content/abstract/149/4/1748}
}
@ARTICLE{Shankavaram2007,
author = {Shankavaram, Uma T. and Reinhold, William C. and Nishizuka, Satoshi
and Major, Sylvia and Morita, Daisaku and Chary, Krishna K. and Reimers,
Mark A. and Scherf, Uwe and Kahn, Ari and Dolginow, Douglas and Cossman,
Jeffrey and Kaldjian, Eric P. and Scudiero, Dominic A. and Petricoin,
Emanuel and Liotta, Lance and Lee, Jae K. and Weinstein, John N.},
title = {Transcript and protein expression profiles of the NCI-60 cancer cell
panel: an integromic microarray study},
journal = {Mol. Cancer Ther.},
year = {2007},
volume = {6},
pages = {820--832},
number = {3},
month = mar,
abstract = {To evaluate the utility of transcript profiling for prediction of
protein expression levels, we compared profiles across the NCI-60
cancer cell panel, which represents nine tissues of origin. For that
analysis, we present here two new NCI-60 transcript profile data
sets (A based on Affymetrix HG-U95 and HG-U133A chips; Affymetrix,
Santa Clara, CA) and one new protein profile data set (based on reverse-phase
protein lysate arrays). The data sets are available online at http://discover.nci.nih.gov
in the CellMiner program package. Using the new transcript data in
combination with our previously published cDNA array and Affymetrix
HU6800 data sets, we first developed a "consensus set" of transcript
profiles based on the four different microarray platforms. Using
that set, we found that 65% of the genes showed statistically significant
transcript-protein correlation, and the correlations were generally
higher than those reported previously for panels of mammalian cells.
Using the predictive analysis of microarray nearest shrunken centroid
algorithm for functional prediction of tissue of origin, we then
found that (a) the consensus mRNA set did better than did data from
any of the individual mRNA platforms and (b) the protein data seemed
to do somewhat better (P = 0.027) on a gene-for-gene basis in this
particular study than did the consensus mRNA data, but both did well.
Analysis based on the Gene Ontology showed protein levels of structure-related
genes to be well predicted by mRNA levels (mean r = 0.71). Because
the transcript-based technologies are more mature and are currently
able to assess larger numbers of genes at one time, they continue
to be useful, even when the ultimate aim is information about proteins.
[Mol Cancer Ther 2007;6(3):820-32]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/6/3/820}
}
@ARTICLE{Shanker2007,
author = {Shanker, Anil and Verdeil, Gregory and Buferne, Michel and Inderberg-Suso,
Else-Marit and Puthier, Denis and Joly, Florence and Nguyen, Catherine
and Leserman, Lee and Auphan-Anezin, Nathalie and Schmitt-Verhulst,
Anne-Marie},
title = {CD8 T Cell Help for Innate Antitumor Immunity},
journal = {J. Immunol.},
year = {2007},
volume = {179},
pages = {6651--6662},
number = {10},
month = nov,
abstract = {Innate immunity is considered to initiate adaptive antitumor responses.
We demonstrate that monoclonal CD8 T lymphocytes reactive to tumor
Ag P1A on P815 mastocytoma cells provide essential "help" to NK cells
for rejection of P1A-deficient tumors. RAG-deficient mice have normal
NK cells but do not reject either tumor. Reconstitution of these
mice with P1A-specific T cells conferred resistance to both P1A-expressing
and -deficient tumor cells provided they were present at the same
site. Elimination of Ag-negative tumor variants required both activated
T and NK cells. Gene expression profiling of NK cells infiltrating
P1A-positive tumors in mice with specific CD8 T cells demonstrated
an activated effector phenotype. However, CD8 T cell help to NK cells
appeared ineffective for P1A-negative variants separated from the
P1A-positive tumor. Local tumor Ag-specific T cell-NK cell collaboration
results in the elimination of tumor cells whether they express or
not the T cell tumor Ag epitope, thus containing the emergence of
tumor escape variants before metastasis.},
url = {http://www.jimmunol.org/cgi/content/abstract/179/10/6651}
}
@ARTICLE{Shanks2011,
author = {Shanks, Orin C. and Kelty, Catherine A. and Archibeque, Shawn and
Jenkins, Michael and Newton, Ryan J. and McLellan, Sandra L. and
Huse, Susan M. and Sogin, Mitchell L.},
title = {Community Structures of Fecal Bacteria in Cattle from Different Animal
Feeding Operations},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {2992--3001},
number = {9},
month = may,
abstract = {The fecal microbiome of cattle plays a critical role not only in animal
health and productivity but also in food safety, pathogen shedding,
and the performance of fecal pollution detection methods. Unfortunately,
most published molecular surveys fail to provide adequate detail
about variability in the community structures of fecal bacteria within
and across cattle populations. Using massively parallel pyrosequencing
of a hypervariable region of the rRNA coding region, we profiled
the fecal microbial communities of cattle from six different feeding
operations where cattle were subjected to consistent management practices
for a minimum of 90 days. We obtained a total of 633,877 high-quality
sequences from the fecal samples of 30 adult beef cattle (5 individuals
per operation). Sequence-based clustering and taxonomic analyses
indicate less variability within a population than between populations.
Overall, bacterial community composition correlated significantly
with fecal starch concentrations, largely reflected in changes in
the Bacteroidetes, Proteobacteria, and Firmicutes populations. In
addition, network analysis demonstrated that annotated sequences
clustered by management practice and fecal starch concentration,
suggesting that the structures of bovine fecal bacterial communities
can be dramatically different in different animal feeding operations,
even at the phylum and family taxonomic levels, and that the feeding
operation is a more important determinant of the cattle microbiome
than is the geographic location of the feedlot.},
comment = {10.1128/AEM.02988-10},
url = {http://aem.asm.org/cgi/content/abstract/77/9/2992}
}
@ARTICLE{Shanks2007,
author = {Shanks, Robert M. Q. and Stella, Nicholas A. and Kalivoda, Eric J.
and Doe, Megan R. and O'Dee, Dawn M. and Lathrop, Kira L. and Guo,
Feng Li and Nau, Gerard J.},
title = {A Serratia marcescens OxyR Homolog Mediates Surface Attachment and
Biofilm Formation},
journal = {J. Bacteriol.},
year = {2007},
volume = {189},
pages = {7262--7272},
number = {20},
month = oct,
abstract = {OxyR is a conserved bacterial transcription factor with a regulatory
role in oxidative stress response. From a genetic screen for genes
that modulate biofilm formation in the opportunistic pathogen Serratia
marcescens, mutations in an oxyR homolog and predicted fimbria structural
genes were identified. S. marcescens oxyR mutants were severely impaired
in biofilm formation, in contrast to the hyperbiofilm phenotype exhibited
by oxyR mutants of Escherichia coli and Burkholderia pseudomallei.
Further analysis revealed that OxyR plays a role in the primary attachment
of cells to a surface. Similar to what is observed in other bacterial
species, S. marcescens OxyR is required for oxidative stress resistance.
Mutations in oxyR and type I fimbrial genes resulted in severe defects
in fimbria-associated phenotypes, revealing roles in cell-cell and
cell-biotic surface interactions. Transmission electron microscopy
revealed the absence of fimbria-like surface structures on an OxyR-deficient
strain and an enhanced fimbrial phenotype in strains bearing oxyR
on a multicopy plasmid. The hyperfimbriated phenotype conferred by
the multicopy oxyR plasmid was absent in a type I fimbrial mutant
background. Real-time reverse transcriptase PCR indicated an absence
of transcripts from a fimbrial operon in an oxyR mutant that were
present in the wild type and a complemented oxyR mutant strain. Lastly,
chromosomal Plac-mediated expression of fimABCD was sufficient to
restore wild-type levels of yeast agglutination and biofilm formation
to an oxyR mutant. Together, these data support a model in which
OxyR contributes to early stages of S. marcescens biofilm formation
by influencing fimbrial gene expression.},
url = {http://jb.asm.org/cgi/content/abstract/189/20/7262}
}
@ARTICLE{Shao2010,
author = {Shao, Chunxuan and Liu, Yuting and Ruan, Hongqiang and Li, Ying and
Wang, Haifang and Kohl, Franziska and Goropashnaya, Anna V. and Fedorov,
Vadim B. and Zeng, Rong and Barnes, Brian M. and Yan, Jun},
title = {Shotgun Proteomics Analysis of Hibernating Arctic Ground Squirrels},
journal = {Mol. Cell. Proteomics},
year = {2010},
volume = {9},
pages = {313--326},
number = {2},
month = feb,
abstract = {Mammalian hibernation involves complex mechanisms of metabolic reprogramming
and tissue protection. Previous gene expression studies of hibernation
have mainly focused on changes at the mRNA level. Large scale proteomics
studies on hibernation have lagged behind largely because of the
lack of an adequate protein database specific for hibernating species.
We constructed a ground squirrel protein database for protein identification
and used a label-free shotgun proteomics approach to analyze protein
expression throughout the torpor-arousal cycle during hibernation
in arctic ground squirrels (Urocitellus parryii). We identified more
than 3,000 unique proteins from livers of arctic ground squirrels.
Among them, 517 proteins showed significant differential expression
comparing animals sampled after at least 8 days of continuous torpor
(late torpid), within 5 h of a spontaneous arousal episode (early
aroused), and 1-2 months after hibernation had ended (non-hibernating).
Consistent with changes at the mRNA level shown in a previous study
on the same tissue samples, proteins involved in glycolysis and fatty
acid synthesis were significantly underexpressed at the protein level
in both late torpid and early aroused animals compared with non-hibernating
animals, whereas proteins involved in fatty acid catabolism were
significantly overexpressed. On the other hand, when we compared
late torpid and early aroused animals, there were discrepancies between
mRNA and protein levels for a large number of genes. Proteins involved
in protein translation and degradation, mRNA processing, and oxidative
phosphorylation were significantly overexpressed in early aroused
animals compared with late torpid animals, whereas no significant
changes at the mRNA levels between these stages had been observed.
Our results suggest that there is substantial post-transcriptional
regulation of proteins during torpor-arousal cycles of hibernation.},
url = {http://www.mcponline.org/cgi/content/abstract/9/2/313}
}
@ARTICLE{Shao2008,
author = {Shao, Chenghua and Novakovic, Valerie A. and Head, James F. and Seaton,
Barbara A. and Gilbert, Gary E.},
title = {Crystal Structure of Lactadherin C2 Domain at 1.7A Resolution with
Mutational and Computational Analyses of Its Membrane-binding Motif},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {7230--7241},
number = {11},
month = mar,
abstract = {Lactadherin is a phosphatidyl-L-serine (Ptd-L-Ser)-binding protein
that decorates membranes of milk fat globules. The major Ptd-L-Ser
binding function of lactadherin has been localized to its C2 domain,
which shares homology with the C2 domains of blood coagulation factor
VIII and factor V. Correlating with this homology, purified lactadherin
competes efficiently with factors VIII and V for Ptd-L-Ser binding
sites, functioning as a potent anticoagulant. We have determined
the crystal structure of the lactadherin C2 domain (Lact-C2) at 1.7A
resolution. The bovine Lact-C2 structure has a {beta}-barrel core
that is homologous with the factor VIII C2 (fVIII-C2) and factor
V C2 (fV-C2) domains. Two loops at the end of the {beta}-barrel,
designated spikes 1 and 3, display four water-exposed hydrophobic
amino acids, reminiscent of the membrane-interactive residues of
fVIII-C2 and fV-C2. In contrast to the corresponding loops in fVIII-C2
and fV-C2, spike 1 of Lact-C2 adopts a hairpin turn in which the
7-residue loop is stabilized by internal hydrogen bonds. Further,
central glycine residues in two membrane-interactive loops may enhance
conformability of Lact-C2 to membrane binding sites. Mutagenesis
studies confirmed a membrane-interactive role for the hydrophobic
and/or Gly residues of both spike 1 and spike 3. Substitution of
spike 1 of fVIII-C2 into Lact-C2 also diminished binding. Computational
ligand docking studies identified two prospective Ptd-L-Ser interaction
sites. These results identify two membrane-interactive loops of Lact-C2
and provide a structural basis for the more efficient phospholipid
binding of lactadherin as compared with factor VIII and factor V.},
url = {http://www.jbc.org/cgi/content/abstract/283/11/7230}
}
@ARTICLE{Shao2007,
author = {Shao, Jing and Stapleton, Patricia L. and Lin, Yvonne S. and Gallagher,
Evan P.},
title = {Cytochrome P450 and Glutathione S-Transferase mRNA Expression in
Human Fetal Liver Hematopoietic Stem Cells},
journal = {Drug Metab. Dispos.},
year = {2007},
volume = {35},
pages = {168--175},
number = {1},
month = jan,
abstract = {During fetal development, the liver serves as the primary hematopoietic
organ in which hematopoietic stem cells (HSC) capable of initiating
long-term hematopoiesis comprise a large proportion of the hepatic
cell population. Although HSC are potential targets for transplacental
chemicals, little is known regarding their xenobiotic biotransformation
ability. We quantitated the steady-state mRNA expression of six cytochrome
P450 (P450) and 11 glutathione S-transferase (GST) isoforms in CD34+-selected
HSC isolated from second trimester human fetal liver donors, genotyped
donors for polymorphic hGSTM1 and hGSTT1 status, and analyzed gene
expression in HSC relative to total liver from donors of similar
gestational ages. Several P450 isoforms, including CYP1A1, CYP2E1,
CYP3A4, and CYP3A5, were expressed at low levels in HSC (relative
mRNA expression CYP3A5 > CYP1A1 > CYP2E1 > CYP3A4). CYP1A2 and CYP3A7
were not detected in HSC. The CYP3A4/5 mRNA expression in HSC was
accompanied by detectable CYP3A protein and low midazolam oxidation
activity. Several GST isoforms, including hGSTM1, hGSTM2, hGSTM4,
and hGSTP1, were significantly higher in HSC as compared with total
fetal liver. With the exception of hGSTA4, alpha class GST were not
detected in HSC. GST expression in HSC was accompanied by substantial
GST catalytic activity toward 1-chloro-2,4-dinitrobenzene. In summary,
our data indicate that fetal liver CD34+-derived HSC constitutively
express several P450 isoforms at low levels relative to total hepatic
cell populations but have a higher capacity for GST conjugation reactions
through mu and pi class isoforms. The functional ramifications of
these observations are discussed relative to the sensitivity of human
fetal HSC to transplacental chemical injury.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/35/1/168}
}
@BOOK{Shapiro2005,
title = {Buying Flow Cytometers},
publisher = {John Wiley \& Sons, Inc.},
year = {2005},
author = {Shapiro, Howard M.},
pages = {411--439},
abstract = {Summary 10.1002/0471722731.ch8.abs This chapter includes the following
topics:},
booktitle = {Practical Flow Cytometry},
issn = {9780471722731},
keywords = {orthodiagnostic system, DakoCytomation, gated amplifier},
url = {http://dx.doi.org/10.1002/0471722731.ch8}
}
@ARTICLE{Sharanowski2010,
author = {Sharanowski, Barbara J. and Robbertse, Barbara and Walker, John and
Voss, S. Randal and Yoder, Ryan and Spatafora, Joseph and Sharkey,
Michael J.},
title = {Expressed sequence tags reveal Proctotrupomorpha (minus Chalcidoidea)
as sister to Aculeata (Hymenoptera: Insecta)},
journal = {Molecular Phylogenetics and Evolution},
year = {2010},
volume = {57},
pages = {101--112},
number = {1},
month = oct,
abstract = {Hymenoptera is one of the most diverse groups of animals on the planet
and have vital importance for ecosystem function as pollinators and
parasitoids. Higher-level relationships among Hymenoptera have been
notoriously difficult to resolve with both morphological and traditional
molecular approaches. Here we examined the utility of expressed sequence
tags for resolving relationships among hymenopteran superfamilies.
Transcripts were assembled for 6 disparate Hymenopteran taxa with
additional sequences added from public databases for a final dataset
of 24 genes for 16 taxa and over 10 kb of sequence data. The concatenated
dataset recovered a robust and well-supported topology demonstrating
the monophyly of Holometabola, Hymenoptera, Apocrita, Aculeata, Ichneumonoidea,
and a sister relationship between the two most closely related proctotrupomorphs
in the dataset (Cynipoidea + Proctotrupoidea). The data strongly
supported a sister relationship between Aculeata and Proctotrupomorpha,
contrary to previously proposed hypotheses. Additionally there was
strong evidence indicating Ichneumonoidea as sister to Aculeata + Proctotrupomorpha.
These relationships were robust to missing data, nucleotide composition
biases, low taxonomic sampling, and conflicting signal across gene
trees. There was also strong evidence indicating that Chalcidoidea
is not contained within Proctotrupomorpha.},
issn = {1055-7903},
keywords = {Expressed sequence tags (ESTs), Hymenoptera, Phylogenomics, Gene tree
discordance, Filtered supernetworks},
url = {http://www.sciencedirect.com/science/article/B6WNH-50HYG6R-5/2/afe80fed5435e482d24f84db6b81991b}
}
@ARTICLE{Sharbati2010,
author = {Sharbati, Soroush and Friedländer, Marc and Sharbati, Jutta and Hoeke,
Lena and Chen, Wei and Keller, Andreas and Stähler, Peer and Rajewsky,
Nikolaus and Einspanier, Ralf},
title = {Deciphering the porcine intestinal microRNA transcriptome},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {275},
number = {1},
abstract = {BACKGROUND:While more than 700 microRNAs (miRNAs) are known in human,
a comparably low number has been identified in swine. Because of
the close phylogenetic distance to humans, pigs serve as a suitable
model for studying e.g. intestinal development or disease. Recent
studies indicate that miRNAs are key regulators of intestinal development
and their aberrant expression leads to intestinal malignancy.RESULTS:Here,
we present the identification of hundreds of apparently novel miRNAs
in the porcine intestine. MiRNAs were first identified by means of
deep sequencing followed by miRNA precursor prediction using the
miRDeep algorithm as well as searching for conserved miRNAs. Second,
the porcine miRNAome along the entire intestine (duodenum, proximal
and distal jejunum, ileum, ascending and transverse colon) was unraveled
using customized miRNA microarrays based on the identified sequences
as well as known porcine and human ones. In total, the expression
of 332 intestinal miRNAs was discovered, of which 201 represented
assumed novel porcine miRNAs. The identified hairpin forming precursors
were in part organized in genomic clusters, and most of the precursors
were located on chromosomes 3 and 1, respectively. Hierarchical clustering
of the expression data revealed subsets of miRNAs that are specific
to distinct parts of the intestine pointing to their impact on cellular
signaling networks.CONCLUSIONS:In this study, we have applied a straight
forward approach to decipher the porcine intestinal miRNAome for
the first time in mammals using a piglet model. The high number of
identified novel miRNAs in the porcine intestine points out their
crucial role in intestinal function as shown by pathway analysis.
On the other hand, the reported miRNAs may share orthologs in other
mammals such as human still to be discovered.},
doi = {10.1186/1471-2164-11-275},
issn = {1471-2164},
pubmedid = {20433717},
url = {http://www.biomedcentral.com/1471-2164/11/275}
}
@ARTICLE{Sharbati-Tehrani2008,
author = {Sharbati-Tehrani, Soroush and Kutz-Lohroff, Barbara and Bergbauer,
Ramona and Scholven, Jutta and Einspanier, Ralf},
title = {miR-Q: a novel quantitative RT-PCR approach for the expression profiling
of small RNA molecules such as miRNAs in a complex sample},
journal = {BMC Molecular Biology},
year = {2008},
volume = {9},
pages = {34},
number = {1},
abstract = {BACKGROUND:MicroRNAs (miRNAs) are small endogenous non-coding interfering
RNA molecules regarded as major regulators in eukaryotic gene expression.
Different methods are employed for miRNA expression profiling. For
a better understanding of their role in essential biological processes,
convenient methods for differential miRNA expression analysis are
required.RESULTS:Here, we present the miR-Q assay as a highly sensitive
quantitative reverse transcription PCR (qRT-PCR) for expression analysis
of small RNAs such as miRNA molecules. It shows a high dynamic range
of 6 to 8 orders of magnitude comprising a sensitivity of up to 0.2
fM miRNA, which corresponds to single copies per cell. There is nearly
no cross reaction among closely-related miRNA family members, which
points to the high specificity of the assays. Using this approach,
we quantified the expression of let-7b in different human cell lines
as well as miR-145 and miR-21 expression in porcine intestinal samples.CONCLUSION:miR-Q
is a cost-effective and highly specific approach, which neither requires
the use of fluorochromic probes, nor Locked Nucleic Acid (LNA)-modified
oligonucleotides. Moreover, it provides a remarkable increase in
specificity and simplified detection of small RNAs.},
doi = {10.1186/1471-2199-9-34},
issn = {1471-2199},
pubmedid = {18400113},
url = {http://www.biomedcentral.com/1471-2199/9/34}
}
@ARTICLE{Sharbati-Tehrani2008a,
author = {Sharbati-Tehrani, Soroush and Kutz-Lohroff, Barbara and Scholven,
Jutta and Einspanier, Ralf},
title = {Concatameric cloning of porcine microRNA molecules after assembly
PCR},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {375},
pages = {484--489},
number = {3},
month = oct,
abstract = {While the number of human or murine microRNAs (miRNAs) increases continuously,
there are limited data available from other species. We report a
novel identification method of small RNAs such as miRNAs, which allows
simultaneous cloning of five RNA molecules within the same insert.
First, RNA molecules <40 nt were polyadenylated and five concatamerising
5' DNA adaptors were ligated to the molecules in independent reactions.
Reverse transcription was carried out using oligo d(T)18 primers
with concatamerising 5' overhangs. The introduced complementary termini
in the different reactions enabled the subsequent coupling of five
purified antisense strands to one molecule by means of an assembly
PCR. After cloning, small RNAs were identified by DNA sequencing.
By means of this cloning approach, we identified 10 novel and one
known porcine miRNAs. Furthermore, the endogenous expression of the
cloned miRNAs was quantified in various tissues using a qRT-PCR approach.},
issn = {0006-291X},
keywords = {microRNA, RNA interference, Cloning, Assembly PCR, miR-Q},
url = {http://www.sciencedirect.com/science/article/B6WBK-4T890SC-B/2/0e11e068add0d9ad5c9f4e0266bf1b59}
}
@ARTICLE{Sharbel2010,
author = {Sharbel, Timothy F. and Voigt, Marie-Luise and Corral, Jose M. and
Galla, Giulio and Kumlehn, Jochen and Klukas, Christian and Schreiber,
Falk and Vogel, Heiko and Rotter, Bjorn},
title = {Apomictic and Sexual Ovules of Boechera Display Heterochronic Global
Gene Expression Patterns},
journal = {PLANT CELL},
year = {2010},
volume = {22},
pages = {655--671},
number = {3},
month = mar,
abstract = {We have compared the transcriptomic profiles of microdissected live
ovules at four developmental stages between a diploid sexual and
diploid apomictic Boechera. We sequenced >2 million SuperSAGE tags
and identified (1) heterochronic tags (n = 595) that demonstrated
significantly different patterns of expression between sexual and
apomictic ovules across all developmental stages, (2) stage-specific
tags (n = 577) that were found in a single developmental stage and
differentially expressed between the sexual and apomictic ovules,
and (3) sex-specific (n = 237) and apomixis-specific (n = 1106) tags
that were found in all four developmental stages but in only one
reproductive mode. Most heterochronic and stage-specific tags were
significantly downregulated during early apomictic ovule development,
and 110 were associated with reproduction. By contrast, most late
stage-specific tags were upregulated in the apomictic ovules, likely
the result of increased gene copy number in apomictic (hexaploid)
versus sexual (triploid) endosperm or of parthenogenesis. Finally,
we show that apomixis-specific gene expression is characterized by
a significant overrepresentation of transcription factor activity.
We hypothesize that apomeiosis is associated with global downregulation
at the megaspore mother cell stage. As the diploid apomict analyzed
here is an ancient hybrid, these data are consistent with the postulated
link between hybridization and asexuality and provide a hypothesis
for multiple evolutionary origins of apomixis in the genus Boechera.},
url = {http://www.plantcell.org/cgi/content/abstract/22/3/655}
}
@ARTICLE{Sharbel2009,
author = {Sharbel, Timothy F. and Voigt, Marie-Luise and Corral, José MarÃa
and Thiel, Thomas and Varshney, Alok and Kumlehn, Jochen and Vogel,
Heiko and Rotter, Björn},
title = {Molecular signatures of apomictic and sexual ovules in the Boechera
holboellii complex},
journal = {The Plant Journal},
year = {2009},
volume = {58},
pages = {870--882},
number = {5},
abstract = {Summary Apomixis, a natural form of asexual seed production in plants,
has evolved independently in various taxa, and represents an important
potential technology for agriculture. The switch to apomixis is based
on de-regulation of developmental pathways originally leading to
sexual seed formation. Hybridization and polyploidy, both typical
characteristics of asexual plants and animals, are mechanisms that
could trigger de-regulation. Here we show that up-regulation of alleles
in apomeiotic ovules is mediated by genomic duplication, heterochrony
and the residual effects of ancient hybridization in diploid apomicts
of the Boechera holboellii complex. Using SuperSAGE, we have identified
over 4000 differentially expressed mRNA tags between micro-dissected
ovules from two diploid sexual (Boechera stricta and B. holboellii)
and two diploid apomictic (Boechera divaricarpa) accessions. Pairwise
sequence comparisons between tags enabled identification of allelic
variants of the same loci. Up-regulated candidate apomeiosis alleles
consistently have more than three related alleles, thus demonstrating
transcription from duplicated loci. A further 543 alleles were heterochronically
expressed between sexual and apomeiotic ovules at developmental stages
2-II to 2-IV. Intriguingly, 69 B. holboellii specific alleles were
preferentially up-regulated in apomeiotic ovules, thus showing a
remnant‘parent of origin’ effect stemming from the Pleistocene
origin of the hybrid B. divaricarpa from taxa related to B. holboellii
and B. stricta. These data implicate polyploid gene dosage in the
expression of asexual seed formation, and support hypotheses of de-regulation
of the sexual pathway. The observed ‘parent of origin’ effect
suggests that the genomic memory of hybridization has somehow been
maintained after hundreds, if not thousands, of asexual generations.},
issn = {1365-313X},
keywords = {apomixis, Boechera, hybridization, gene duplication, gene expression,
parent of origin effect},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2009.03826.x}
}
@ARTICLE{Sharif-Askari2007,
author = {Sharif-Askari, Ehssan and Nakhaei, Peyman and Oliere, Stephanie and
Tumilasci, Vanessa and Hernandez, Eduardo and Wilkinson, Peter and
Lin, Rongtuan and Bell, John and Hiscott, John},
title = {Bax-dependent mitochondrial membrane permeabilization enhances IRF3-mediated
innate immune response during VSV infection},
journal = {Virology},
year = {2007},
volume = {365},
pages = {20--33},
number = {1},
month = aug,
abstract = {An effective type I interferon (IFN-[alpha]/[beta]) response is critical
for the control of many viral infections. Using an oncolytic strain
of vesicular stomatitis virus, we have examined the cross-talk between
virus-induced apoptosis and initiation of innate immune response.
The intrinsic apoptotic cascade, specifically the Bax-Bcl-2-Caspase-9
cascade, was revealed as the primary pathway of VSV-induced apoptosis.
Cell death was significantly reduced in BaxBak-/- murine embryonic
fibroblasts (MEFs) and in human A549 epithelial cells treated with
siRNA against Bax. Although inhibition of apoptosis resulted in enhanced
virus replication in the BaxBak-/- MEFs as compared to wild-type
cells, induction of the IFN antiviral response and expression of
cytokine genes were attenuated in virus-infected cells. Moreover,
Bax but not Bak pro-apoptotic protein was required for IRF-3 phosphorylation
and activation, further substantiating a role for the intrinsic mitochondrial
pathway in the innate immune response. Therefore, virus-induced apoptosis
through a Bax-dependent mitochondrial pathway appears to enhance
the full development of the IRF-3 mediated IFN antiviral response.},
issn = {0042-6822},
keywords = {Mitochondria, IRF-3, Innate immunity, VSV, Bax},
url = {http://www.sciencedirect.com/science/article/B6WXR-4NJP3H9-1/2/e4702b9ab1eb7b4e119237a59ccc4048}
}
@ARTICLE{Sharkey2004,
author = {Sharkey, Freddie H. and Banat, Ibrahim M. and Marchant, Roger},
title = {Detection and Quantification of Gene Expression in Environmental
Bacteriology},
journal = {Appl. Envir. Microbiol.},
year = {2004},
volume = {70},
pages = {3795--3806},
number = {7},
month = jul,
url = {http://aem.asm.org}
}
@ARTICLE{Sharkhuu2010,
author = {Sharkhuu, Tuya and Doerfler, Donald L. and Krantz, Q. Todd and Luebke,
Robert W. and Linak, William P. and Gilmour, M. Ian},
title = {Effects of prenatal diesel exhaust inhalation on pulmonary inflammation
and development of specific immune responses},
journal = {Toxicology Letters},
year = {2010},
volume = {196},
pages = {12--20},
number = {1},
month = jun,
abstract = {There is increasing evidence that exposure to air pollutants during
pregnancy can result in a number of deleterious effects including
low birth weight and the incidence of allergic asthma. To investigate
the in utero effects of DE exposure, timed pregnant BALB/c mice were
exposed to 0, 0.8 or 3.1 mg/m3 of DE during gestation days (GD) 9
to GD 18. The number of successful pregnancies was 15/20 in the air
controls and 10/20 in each of the diesel exposures. Immune function
in the 6-week-old offspring as determined by development of delayed
type hypersensitivity (DTH) reactions to bovine serum albumin (BSA),
antibody titers to injected sheep red blood cells (SRBC), splenic
T cells expressing CD45+CD3+CD8+ and CD3+CD25+, and mRNA expression
of TNF-[alpha], TLR2, SP-A, TGF-[beta] and Foxp3 in the lung were
not affected by prenatal DE exposure. On the other hand, lung TLR4
mRNA expression, the number of neutrophils in the bronchoalveolar
lavage fluid (BALF) and splenic T cells expressing CD45+CD3+CD4+
and CD4+CD25+ were differentially affected depending on the DE concentration
and gender. When additional groups of mice were sensitized and challenged
via the respiratory tract with ovalbumin to induce allergic airway
inflammation, female mice had higher protein levels in the BALF compared
to males and this was reduced by prenatal exposure to either concentration
of DE. No other changes in allergen-induced immunity, lung function
or severity of inflammation were noted. Collectively, the results
show that in utero exposure to DE altered some baseline inflammatory
indices in the lung in a gender-specific manner, but had no effect
on development of specific immune responses to experimental antigens,
or the severity of allergic lung inflammation.},
issn = {0378-4274},
keywords = {Diesel, In utero exposure, Toxicity, Immunity, Allergy},
url = {http://www.sciencedirect.com/science/article/B6TCR-4YRPDRX-4/2/6bb6247596fd811522f7316d4845367c}
}
@ARTICLE{Sharma2011a,
author = {Sharma, Amar Deep and Narain, Nidhi and Händel, Eva-Maria and Iken,
Marcus and Singhal, Nishant and Cathomen, Toni and Manns, Michael
P. and Schöler, Hans R. and Ott, Michael and Cantz, Tobias},
title = {MicroRNA-221 regulates FAS-induced fulminant liver failure},
journal = {Hepatology},
year = {2011},
volume = {53},
pages = {1651--1661},
number = {5},
abstract = {Abstract Death receptor-mediated apoptosis of hepatocytes contributes
to hepatitis and fulminant liver failure. MicroRNAs (miRNAs), 19-25
nucleotide-long noncoding RNAs, have been implicated in the posttranscriptional
regulation of the various apoptotic pathways. Here we report that
global loss of miRNAs in hepatic cells leads to increased cell death
in a model of FAS/CD95 receptor-induced apoptosis. miRNA profiling
of murine liver identified 11 conserved miRNAs, which were up-regulated
in response to FAS-induced fulminant liver failure. We show that
ectopic expression of miR-221, one of the highly up-regulated miRNAs
in response to apoptosis, protects primary hepatocytes and hepatoma
cells from apoptosis. Importantly, in vivo overexpression of miR-221
by adeno-associated virus serotype 8 (AAV8) delays FAS-induced fulminant
liver failure in mice. We additionally demonstrate that miR-221 regulates
hepatic expression of p53 up-regulated modulator of apoptosis (Puma),
a well-known proapoptotic member of the Bcl2 protein family. Conclusion:
We identified miR-221 as a potent posttranscriptional regulator of
FAS-induced apoptosis. miR-221 may serve as a potential therapeutic
target for the treatment of hepatitis and liver failure. (HEPATOLOGY
2011;)},
doi = {10.1002/hep.24243},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.24243}
}
@ARTICLE{Sharma2007,
author = {Sharma, Mukesh K. and Mansur, David B. and Reifenberger, Guido and
Perry, Arie and Leonard, Jeffrey R. and Aldape, Kenneth D. and Albin,
Meredith G. and Emnett, Ryan J. and Loeser, Simon and Watson, Mark
A. and Nagarajan, Rakesh and Gutmann, David H.},
title = {Distinct Genetic Signatures among Pilocytic Astrocytomas Relate to
Their Brain Region Origin},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {890--900},
number = {3},
month = feb,
abstract = {Pilocytic astrocytomas (PAs) are the most common glioma in children.
Whereas many PAs are slow-growing or clinically indolent, others
exhibit more aggressive features with tumor recurrence and death.
To identify genetic signatures that might predict PA clinical behavior,
we did gene expression profiling on 41 primary PAs arising sporadically
and in patients with neurofibromatosis type 1 (NF1). Whereas no expression
signature was found that could discriminate clinically aggressive
or recurrent tumors from more indolent cases, PAs arising in patients
with NF1 did exhibit a unique gene expression pattern. In addition,
we identified a gene expression signature that stratified PAs by
location (supratentorial versus infratentorial). Lastly, we also
identified a gene expression pattern common to PAs and normal mouse
astrocytes and neural stem cells from these distinct brain regions
as well as a gene expression pattern shared between PAs and another
human glial tumor (ependymoma) arising supratentorially compared
with those originating in the posterior fossa. These results suggest
that glial tumors share an intrinsic, lineage-specific molecular
signature that reflects the brain region in which their nonmalignant
predecessors originated. [Cancer Res 2007;67(3):890-900]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/3/890}
}
@ARTICLE{Sharma2008,
author = {Sharma, Neeraj K. and Das, Swapan K. and Mondal, Ashis K. and Hackney,
Oksana G. and Chu, Winston S. and Kern, Philip A. and Rasouli, Neda
and Spencer, Horace J. and Yao-Borengasser, Aiwei and Elbein, Steven
C.},
title = {Endoplasmic Reticulum Stress Markers Are Associated with Obesity
in Nondiabetic Subjects},
journal = {J. Clin. Endocrinol. Metab.},
year = {2008},
volume = {93},
pages = {4532--4541},
number = {11},
month = nov,
abstract = {Objective: Adipocyte and hepatocyte endoplasmic reticulum (ER) stress
response is activated in dietary and genetic models of obesity in
mice. We hypothesized that ER stress was also activated and associated
with reduced insulin sensitivity (SI) in human obesity. Research
Design and Methods: We recruited 78 healthy, nondiabetic individuals
over a spectrum of body mass index (BMI) who underwent oral and iv
glucose tolerance tests, and fasting sc adipose and muscle biopsies.
We tested expression of 18 genes and levels of total and phosphorylated
eukaryotic initiation factor 2{alpha}, c-jun, and c-Jun N-terminal
kinase 1 in adipose tissue. We compared gene expression in stromal
vascular and adipocyte fractions in paired samples from 22 individuals,
and tested clustering on gene and protein markers. Results: Adipocyte
expression of most markers of ER stress, including chaperones downstream
of activating transcription factor 6, were significantly correlated
with BMI and percent fat (r > 0.5; P < 0.00001). Phosphorylation
of eukaryotic initiation factor 2{alpha} but not of c-Jun N-terminal
kinase 1 or c-jun was increased with obesity. ER stress response
(as elsewhere) was also increased with obesity in a second set of
86 individuals, and in the combined sample (n = 161). The increase
was only partially attributable to the stromal vascular fraction
and macrophage infiltration. ER stress markers were only modestly
correlated with SI. Clustering algorithms supported ER stress activation
with high BMI but not low SI. Conclusions: Multiple markers of ER
stress are activated in human adipose with obesity, particularly
for protective chaperones downstream of activating transcription
factor 6{alpha}.},
url = {http://jcem.endojournals.org/cgi/content/abstract/93/11/4532}
}
@ARTICLE{Sharma2010a,
author = {Sharma, Neena K. and Ryals, Janelle M. and Gajewski, Byron J. and
Wright, Douglas E.},
title = {Aerobic Exercise Alters Analgesia and Neurotrophin-3 Synthesis in
an Animal Model of Chronic Widespread Pain},
journal = {Physical Therapy},
year = {2010},
volume = {90},
pages = {714--725},
number = {5},
month = may,
abstract = {BackgroundPresent literature and clinical practice provide strong
support for the use of aerobic exercise in reducing pain and improving
function for individuals with chronic musculoskeletal pain syndromes.
However, the molecular basis for the positive actions of exercise
remains poorly understood. Recent studies suggest that neurotrophin-3
(NT-3) may act in an analgesic fashion in various pain states. ObjectiveThe
purpose of the present study was to examine the effects of moderate-intensity
aerobic exercise on pain-like behavior and NT-3 in an animal model
of widespread pain. DesignThis was a repeated-measures, observational
cross-sectional study. MethodsForty female mice were injected with
either normal (pH 7.2; n=20) or acidic (pH 4.0; n=20) saline in the
gastrocnemius muscle to induce widespread hyperalgesia and exercised
for 3 weeks. Cutaneous (von Frey monofilament) and muscular (forceps
compression) mechanical sensitivity were assessed. Neurotrophin-3
was quantified in 2 hind-limb skeletal muscles for both messenger
RNA (mRNA) and protein levels after exercise training. Data were
analyzed with 2-factor analysis of variance for repeated measures
(group x time). ResultsModerate-intensity aerobic exercise reduced
cutaneous and deep tissue hyperalgesia induced by acidic saline and
stimulated NT-3 synthesis in skeletal muscle. The increase in NT-3
was more pronounced at the protein level compared with mRNA expression.
In addition, the increase in NT-3 protein was significant in the
gastrocnemius muscle but not in the soleus muscle, suggesting that
exercise can preferentially target NT-3 synthesis in specific muscle
types. LimitationsResults are limited to animal models and cannot
be generalized to chronic pain syndromes in humans. ConclusionsThis
is the first study demonstrating the effect of exercise on deep tissue
mechanical hyperalgesia in a rodent model of pain and providing a
possible molecular basis for exercise training in reducing muscular
pain.},
url = {http://ptjournal.apta.org/cgi/content/abstract/90/5/714}
}
@ARTICLE{Sharma2011,
author = {Sharma, Sunita and Murphy, Amy and Howrylak, Judie and Himes, Blanca
and Cho, Michael H. and Chu, Jen-Hwa and Hunninghake, Gary M. and
Fuhlbrigge, Anne and Klanderman, Barbara and Ziniti, John and Senter-Sylvia,
Jody and Liu, Andy and Szefler, Stanley J. and Strunk, Robert and
Castro, Mario and Hansel, Nadia N. and Diette, Gregory B. and Vonakis,
Becky M. and Adkinson, N. Franklin and Carey, Vincent J. and Raby,
Benjamin A.},
title = {The impact of self-identified race on epidemiologic studies of gene
expression},
journal = {Genetic Epidemiology},
year = {2011},
volume = {35},
pages = {93--101},
number = {2},
abstract = {Abstract Although population differences in gene expression have been
established, the impact on differential gene expression studies in
large populations is not well understood. We describe the effect
of self-reported race on a gene expression study of lung function
in asthma. We generated gene expression profiles for 254 young adults
(205 non-Hispanic whites and 49 African Americans) with asthma on
whom concurrent total RNA derived from peripheral blood CD4+ lymphocytes
and lung function measurements were obtained. We identified four
principal components that explained 62% of the variance in gene expression.
The dominant principal component, which explained 29% of the total
variance in gene expression, was strongly associated with self-identified
race (P<10−16). The impact of these racial differences was observed
when we performed differential gene expression analysis of lung function.
Using multivariate linear models, we tested whether gene expression
was associated with a quantitative measure of lung function: pre-bronchodilator
forced expiratory volume in one second (FEV1). Though unadjusted
linear models of FEV1 identified several genes strongly correlated
with lung function, these correlations were due to racial differences
in the distribution of both FEV1 and gene expression, and were no
longer statistically significant following adjustment for self-identified
race. These results suggest that self-identified race is a critical
confounding covariate in epidemiologic studies of gene expression
and that, similar to genetic studies, careful consideration of self-identified
race in gene expression profiling studies is needed to avoid spurious
association. Genet. Epidemiol. 32:93–101, 2011. © 2011 Wiley-Liss,
Inc.},
doi = {10.1002/gepi.20560},
issn = {1098-2272},
keywords = {ancestry, gene expression, population stratification, self-identified
race},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gepi.20560}
}
@ARTICLE{Sharma2010b,
author = {Sharma, Sunita and Tantisira, Kelan and Carey, Vincent and Murphy,
Amy J. and Lasky-Su, Jessica and Celedon, Juan C. and Lazarus, Ross
and Klanderman, Barbara and Rogers, Angela and Soto-Quiros, Manuel
and Avila, Lydiana and Mariani, Thomas and Gaedigk, Roger and Leeder,
Stephen and Torday, John and Warburton, David and Raby, Benjamin
and Weiss, Scott T.},
title = {A Role for Wnt Signaling Genes in the Pathogenesis of Impaired Lung
Function in Asthma},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2010},
volume = {181},
pages = {328--336},
number = {4},
month = feb,
abstract = {Rationale: Animal models demonstrate that aberrant gene expression
in utero can result in abnormal pulmonary phenotypes. Objectives:
We sought to identify genes that are differentially expressed during
in utero airway development and test the hypothesis that variants
in these genes influence lung function in patients with asthma. Methods:
Stage 1 (Gene Expression): Differential gene expression analysis
across the pseudoglandular (n = 27) and canalicular (n = 9) stages
of human lung development was performed using regularized t tests
with multiple comparison adjustments. Stage 2 (Genetic Association):
Genetic association analyses of lung function (FEV1, FVC, and FEV1/FVC)
for variants in five differentially expressed genes were conducted
in 403 parent-child trios from the Childhood Asthma Management Program
(CAMP). Associations were replicated in 583 parent-child trios from
the Genetics of Asthma in Costa Rica study. Measurements and Main
Results: Of the 1,776 differentially expressed genes between the
pseudoglandular (gestational age: 7-16 wk) and the canalicular (gestational
age: 17-26 wk) stages, we selected 5 genes in the Wnt pathway for
association testing. Thirteen single nucleotide polymorphisms in
three genes demonstrated association with lung function in CAMP (P
< 0.05), and associations for two of these genes were replicated
in the Costa Ricans: Wnt1-inducible signaling pathway protein 1 with
FEV1 (combined P = 0.0005) and FVC (combined P = 0.0004), and Wnt
inhibitory factor 1 with FVC (combined P = 0.003) and FEV1/FVC (combined
P = 0.003). Conclusions: Wnt signaling genes are associated with
impaired lung function in two childhood asthma cohorts. Furthermore,
gene expression profiling of human fetal lung development can be
used to identify genes implicated in the pathogenesis of lung function
impairment in individuals with asthma.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/181/4/328}
}
@BOOK{Sharma2010,
title = {Experimental Detection and Characterization of Protein Aggregates},
publisher = {John Wiley \& Sons, Inc.},
year = {2010},
author = {Sharma, Vikas K. and Kalonia, Devendra S.},
pages = {205--256},
abstract = {Summary 10.1002/9780470769829.ch5.abs This chapter contains sections
titled:},
booktitle = {Aggregation of Therapeutic Proteins},
issn = {9780470769829},
keywords = {experimental detection and characterization of protein aggregates,
intrinsic tryptophan fluorescence spectroscopy - tryptophan microenvironment
within protein, appropriate analytical techniques - to characterize
and quantitate types of aggregates},
url = {http://dx.doi.org/10.1002/9780470769829.ch5}
}
@ARTICLE{Sharp2011,
author = {Sharp, B. M. and Chen, H. and Gong, S. and Wu, X. and Liu, Z. and
Hiler, K. and Taylor, W. L. and Matta, S. G.},
title = {Gene expression in accumbens GABA neurons from inbred rats with different
drug-taking behavior},
journal = {Genes, Brain and Behavior},
year = {2011},
volume = {10},
pages = {778--788},
number = {7},
abstract = {Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration;
Lewis rats operantly self-administer drugs of abuse including nicotine,
whereas Fisher self-administer poorly. As shown herein, operant food
self-administration is similar. On the basis of their pivotal role
in drug reward, we hypothesized that differences in basal gene expression
in GABAergic neurons projecting from nucleus accumbens (NAcc) to
ventral pallidum (VP) play a role in vulnerability to drug-taking
behavior. The transcriptomes of NAcc shell-VP GABAergic neurons from
these two strains were analyzed in adolescents, using a multidisciplinary
approach that combined stereotaxic ionotophoretic brain microinjections,
laser-capture microdissection (LCM) and microarray measurement of
transcripts. Laser-capture microdissection enriched the gene transcripts
detected in gamma-aminobutyric acid (GABA) neurons compared to the
residual NAcc tissue: a ratio of neuron/residual >1 and false discovery
rate (FDR) <5% yielded 6623 transcripts, whereas a ratio of >3 yielded
3514. Strain-dependent differences in gene expression within GABA
neurons were identified; 322 vs. 60 transcripts showed 1.5-fold vs.
2-fold differences in expression (FDR < 5%). Classification by gene
ontology showed that these 322 transcripts were widely distributed,
without categorical enrichment. This is most consistent with a global
change in GABA neuron function. Literature mining by Chilibot found
38 genes related to synaptic plasticity, signaling and gene transcription,
all of which determine drug abuse; 33 genes have no known association
with addiction or nicotine. In Lewis rats, upregulation of Mint-1,
Cask, CamkII, Ncam1, Vsnl1, Hpcal1 and Car8 indicates that these
transcripts likely contribute to altered signaling and synaptic function
in NAcc GABA projection neurons to VP.},
doi = {10.1111/j.1601-183X.2011.00716.x},
issn = {1601-183X},
keywords = {Addiction, Fisher 344 rats, GABA, laser-capture microdissection, Lewis
rats, nicotine, nucleus accumbens, synapse, transcriptome, ventral
pallidum},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1601-183X.2011.00716.x}
}
@ARTICLE{Sharp2010,
author = {Sharp, Jonathan O. and Sales, Christopher M. and Alvarez-Cohen, Lisa},
title = {Functional characterization of propane-enhanced N-nitrosodimethylamine
degradation by two actinomycetales},
journal = {Biotechnol. Bioeng.},
year = {2010},
volume = {107},
pages = {924--932},
number = {6},
abstract = {Abstract Propane-induced cometabolic degradation of n-nitrosodimethylamine
(NDMA) by two propanotrophs is characterized through kinetic, gene
presence, and expression studies. After growth on propane, resting
cells of Rhodococcus sp. RR1 possessed a maximum transformation rate
(vmax,n) of 44 ± 5 µg NDMA (mg protein)−1 h−1;
the rate for Mycobacterium vaccae (austroafricanum) JOB-5 was modestly
lower with vmax,n of 28 ± 3 µg NDMA (mg protein)−1 h−1.
Both strains were capable of degrading environmentally relevant,
trace quantities of NDMA to below the experimental limit of detection,
calculated as 20 ng NDMA L−1. However, a comparison of half
saturation constants (Ks,n) and NDMA degradation in the presence
of propane revealed pronounced differences between the strains. The
Ks,n for strain RR1 was 36 ± 10 µg NDMA L−1 while the
propane concentration needed to inhibit NDMA rates by 50% (Kinh)
occurred at 7,700 µg propane L−1 (R2 = 0.9669). In contrast,
strain JOB-5 had a markedly lower affinity for NDMA verses propane
with a calculated Ks,n of 2,200 ± 1,000 µg NDMA L−1
and Kinh of 120 µg propane L−1 (R2 = 0.9895). Genomic
and transcriptional investigations indicated that the functional
enzymes involved in NDMA degradation and propane metabolism are different
for each strain. For Rhodococcus sp. RR1, a putative propane monooxygenase
(PrMO) was identified and implicated in NDMA oxidation. In contrast,
JOB-5 was not found to possess a PrMO homologue and two functionally
analogous alkane monoxygenases (AlkMOs) were not induced by growth
on propane. Differences between the PrMO in this Rhodococcus and
the unidentified enzyme(s) in the Mycobacterium may explain differences
in NDMA degradation and inhibition kinetics between these strains.
Biotechnol. Bioeng. 2010;107: 924–932. © 2010 Wiley Periodicals,
Inc.},
issn = {1097-0290},
keywords = {cometabolism, monooxygenase, Monod, biodegradation, competition, NDMA},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22899}
}
@ARTICLE{Shaughnessy2009,
author = {Shaughnessy, Ronan G. and Meade, Kieran G. and Cahalane, Sarah and
Allan, Brenda and Reiman, Carla and Callanan, John J. and O'Farrelly,
Cliona},
title = {Innate immune gene expression differentiates the early avian intestinal
response between Salmonella and Campylobacter},
journal = {Veterinary Immunology and Immunopathology},
year = {2009},
volume = {132},
pages = {191--198},
number = {2-4},
month = dec,
abstract = {Salmonella enterica serovar Typhimurium and Campylobacter jejuni are
major human pathogens, yet colonise chickens without causing pathology.
The aim of this study was to compare intestinal innate immune responses
to both bacterial species, in a 4-week-old broiler chicken model.
Challenged and control birds were sacrificed and tissue samples taken
for histopathology and RNA extraction. No significant clinical or
pathological changes were observed in response to infection with
either bacterial species. Expression of selected genes involved in
pathogen detection and the innate immune response were profiled in
caecal tissues by quantitative real-time PCR. TLR4 and TLR21 gene
expression was transiently increased in response to both bacterial
species (P < 0.05). Significant increases in TLR5 and TLR15 gene
expression were detected in response to S. Typhimurium but not to
C. jejuni. Transient increases of proinflammatory cytokine (IL6 and
IFNG) and chemokine (IL8 and K60) genes increased as early as 6 h
in response to S. Typhimurium. Minimal cytokine gene expression was
detected in response to C. jejuni after 20 h. IL8 gene expression
however, was significantly increased by 24-fold (P < 0.01). The differential
expression profiles of innate immune genes in both infection models
shed light on the tailored responses of the host immune system to
specific microbes. It is further evidence that innate regulation
of these responses is an important prerequisite to preventing development
of disease.},
issn = {0165-2427},
keywords = {Chicken, Commensal, Campylobacter, Salmonella, Innate immune gene
expression},
url = {http://www.sciencedirect.com/science/article/B6TD5-4WK43N8-1/2/100156438f509dd63f4c310800ac91ef}
}
@ARTICLE{Shaughnessy2011,
author = {Ronan G. Shaughnessy and Kieran G. Meade and Beatrice A. McGivney
and Brenda Allan and Cliona O’Farrelly},
title = {Global gene expression analysis of chicken caecal response to Campylobacter
jejuni},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {142},
pages = {64 - 71},
number = {1–2},
abstract = {Campylobacter jejuni colonises the caecum of more than 90% of commercial
chickens. Even though colonisation is asymptomatic, we hypothesised
that it is mediated by activation of several biological pathways.
We therefore used chicken-specific 20K oligonucleotide microarrays
to examine global gene expression in C. jejuni-challenged birds.
Microarray results demonstrate small but significant fold-changes
in expression of 270 genes 20 h post-challenge, corresponding
to a wide range of biological processes including cell growth, nutrient
metabolism and immunological activity. Expression of NOX1 (2.3-fold)
and VCAM1 (1.5-fold) were significantly increased in colonised birds
(P < 0.05), indicating oxidative burst and endothelial
cell activation, respectively. Microarray results, supplemented by
qRT-PCR analyses demonstrated increased TOPK (1.9-fold), IL17 (3.6-fold),
IL21 (2.1-fold), IL7R (4-fold) and CTLA4 (2.5-fold) gene expression
(P < 0.05), which was suggestive of T cell mediated
activity. Combined these results suggest that C. jejuni has nominal
effects on global caecal gene expression in the chicken but significant
changes detected are suggestive of a protective intestinal T cell
response.},
doi = {10.1016/j.vetimm.2011.04.010},
issn = {0165-2427},
keywords = {Chicken},
url = {http://www.sciencedirect.com/science/article/pii/S0165242711001279}
}
@ARTICLE{Shaw2007,
author = {Shaw, A.E. and Monaghan, P. and Alpar, H.O. and Anthony, S. and Darpel,
K.E. and Batten, C.A. and Guercio, A. and Alimena, G. and Vitale,
M. and Bankowska, K. and Carpenter, S. and Jones, H. and Oura, C.A.L.
and King, D.P. and Elliott, H. and Mellor, P.S. and Mertens, P.P.C.},
title = {Development and initial evaluation of a real-time RT-PCR assay to
detect bluetongue virus genome segment 1},
journal = {Journal of Virological Methods},
year = {2007},
volume = {145},
pages = {115--126},
number = {2},
month = nov,
abstract = {Since 1998, multiple strains of bluetongue virus (BTV), belonging
to six different serotypes (types 1, 2, 4, 8, 9 and 16) have caused
outbreaks of disease in Europe, causing one of the largest epizootics
of bluetongue ever recorded, with the deaths of >1.8 million animals
(mainly sheep). The persistence and continuing spread of BTV in Europe
and elsewhere highlights the importance of sensitive and reliable
diagnostic assay systems that can be used to rapidly identify infected
animals, helping to combat spread of the virus and disease. BTV has
a genome composed of 10 linear segments of dsRNA. We describe a real-time
RT-PCR assay that targets the highly conserved genome segment 1 (encoding
the viral polymerase--VP1) that can be used to detect all of the
24 serotypes, as well as geographic variants (different topotypes)
within individual serotypes of BTV. After an initial evaluation using
132 BTV samples including representatives of all 24 BTV serotypes,
this assay was used by the European Community Reference Laboratory
(CRL) at IAH Pirbright to confirm the negative status of 2255 animals
imported to the UK from regions that were considered to be at risk
during the 2006 outbreak of BTV-8 in Northern Europe. All of these
animals were also negative by competition ELISA to detect BTV specific
antibodies and none of them developed clinical signs of infection.
These studies have demonstrated the value of the assay for the rapid
screening of field samples.},
issn = {0166-0934},
keywords = {Bluetongue virus, Real-time RT-PCR, Diagnosis},
url = {http://www.sciencedirect.com/science/article/B6T96-4P18B2H-2/2/f4fe89b396336cec58dbefe6dda77d48}
}
@ARTICLE{Shaw2007a,
author = {Shaw, Joseph and Colbourne, John and Davey, Jennifer and Glaholt,
Stephen and Hampton, Thomas and Chen, Celia and Folt, Carol and Hamilton,
Joshua},
title = {Gene response profiles for Daphnia pulex exposed to the environmental
stressor cadmium reveals novel crustacean metallothioneins},
journal = {BMC Genomics},
year = {2007},
volume = {8},
pages = {477},
number = {1},
abstract = {BACKGROUND:Genomic research tools such as microarrays are proving
to be important resources to study the complex regulation of genes
that respond to environmental perturbations. A first generation cDNA
microarray was developed for the environmental indicator species
Daphnia pulex, to identify genes whose regulation is modulated following
exposure to the metal stressor cadmium. Our experiments revealed
interesting changes in gene transcription that suggest their biological
roles and their potentially toxicological features in responding
to this important environmental contaminant.RESULTS:Our microarray
identified genes reported in the literature to be regulated in response
to cadmium exposure, suggested functional attributes for genes that
share no sequence similarity to proteins in the public databases,
and pointed to genes that are likely members of expanded gene families
in the Daphnia genome. Genes identified on the microarray also were
associated with cadmium induced phenotypes and population-level outcomes
that we experimentally determined. A subset of genes regulated in
response to cadmium exposure was independently validated using quantitative-realtime
(Q-RT)-PCR. These microarray studies led to the discovery of three
genes coding for the metal detoxication protein metallothionein (MT).
The gene structures and predicted translated sequences of D. pulex
MTs clearly place them in this gene family. Yet, they share little
homology with previously characterized MTs.CONCLUSION:The genomic
information obtained from this study represents an important first
step in characterizing microarray patterns that may be diagnostic
to specific environmental contaminants and give insights into their
toxicological mechanisms, while also providing a practical tool for
evolutionary, ecological, and toxicological functional gene discovery
studies. Advances in Daphnia genomics will enable the further development
of this species as a model organism for the environmental sciences.},
doi = {10.1186/1471-2164-8-477},
issn = {1471-2164},
owner = {Meike Kuschel},
pubmedid = {18154678},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2164/8/477}
}
@ARTICLE{Shaw2010,
author = {Shaw, Joseph R. and Bomberger, Jennifer M. and VanderHeide, John
and LaCasse, Taylor and Stanton, Sara and Coutermarsh, Bonita and
Barnaby, Roxanna and Stanton, Bruce A.},
title = {Arsenic inhibits SGK1 activation of CFTR Cl- channels in the gill
of killifish, Fundulus heteroclitus},
journal = {Aquatic Toxicology},
year = {2010},
volume = {98},
pages = {157--164},
number = {2},
month = jun,
abstract = {Seawater acclimation in killifish, Fundulus heteroclitus, is mediated
in part by a rapid (1 h) translocation of CFTR Cl- channels from
an intracellular pool to the plasma membrane in gill and increased
CFTR-mediated Cl- secretion. This effect is mediated by serum and
glucocorticoid-inducible kinase 1 (SGK1), which is stimulated by
plasma hypertonicity rather than cortisol. Since arsenic exposure
prevents acclimation to seawater by decreasing CFTR protein levels
we tested the hypothesis that arsenic (as sodium arsenite) blocks
acclimation to seawater by down regulating SGK1 expression. Freshwater
adapted killifish were exposed to arsenic (48 h) and transferred
to seawater containing arsenic, and SGK and CFTR expression were
measured. Arsenic reduced the seawater induced increase in SGK1 mRNA
and protein abundance, and reduced both the total amount of CFTR
and the amount of CFTR in the plasma membrane. The decrease in membrane
CFTR reduced Cl- secretion. Arsenic also increased the amount of
ubiquitinated CFTR and its degradation by the lysosome. Thus, we
propose a model whereby arsenic reduces the ability of killifish
to acclimate to seawater by blocking the seawater induced increase
in SGK1, which results in increased ubiquitination and degradation
of CFTR.},
issn = {0166-445X},
keywords = {Acclimation, Ubiquitination, Lysosome, Abcc7, Environmental toxicant},
url = {http://www.sciencedirect.com/science/article/B6T4G-4YB5KYY-4/2/d9b5b61bd32c51e364d74d5611f097d9}
}
@ARTICLE{Shaw2007b,
author = {Shaw, Joseph R. and Gabor, Kristen and Hand, Emily and Lankowski,
Alexander and Durant, Lydia and Thibodeau, Renee and Stanton, Caitlin
R. and Barnaby, Roxanna and Coutermarsh, Bonita and Karlson, Katherine
H. and Sato, J. Denry and Hamilton, Joshua W. and Stanton, Bruce
A.},
title = {Role of glucocorticoid receptor in acclimation of killifish (Fundulus
heteroclitus) to seawater and effects of arsenic},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {292},
pages = {R1052--1060},
number = {2},
month = feb,
abstract = {Killifish are euryhaline teleosts that adapt to rapid changes in the
salinity of the seawater. It is generally accepted that acclimation
to seawater is mediated by cortisol activation of the glucocorticoid
receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated
Cl- secretion by the gill. Because there is no direct evidence in
killifish that the GR stimulates CFTR gene expression, quantitative
PCR studies were conducted to test the hypothesis that cortisol activation
of GR upregulates CFTR mRNA expression and that this response is
required for acclimation to seawater. Inhibition of the GR by RU-486
prevented killifish from acclimating to increased salinity and blocked
the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid
receptor by spironolactone had no effect on acclimation to seawater.
Thus acclimation to increased salinity in killifish requires signaling
via the GR and includes an increase in CFTR gene expression. Because
arsenic, a toxic metalloid that naturally occurs in the aquatic environment,
has been shown to disrupt GR transcriptional regulation in avian
and mammalian systems, studies were also conducted to determine whether
arsenic disrupts cortisol-mediated activation of CFTR gene expression
in this in vivo fish model and thereby blocks the ability of killifish
to acclimate to increased salinity. Arsenic prevented acclimation
to seawater and decreased CFTR protein abundance. However, arsenic
did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic
blocks acclimation to seawater in killifish by a mechanism that does
not disrupt GR-mediated induction of CFTR gene expression.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/292/2/R1052}
}
@ARTICLE{Shaw2007c,
author = {Shaw, Joseph R. and Jackson, Brian and Gabor, Kristin and Stanton,
Sara and Hamilton, Joshua W. and Stanton, Bruce A.},
title = {The influence of exposure history on arsenic accumulation and toxicity
in the killifish, Fundulus heteroclitus},
journal = {Environmental Toxicology and Chemistry},
year = {2007},
volume = {26},
pages = {2704--2709},
number = {12},
abstract = {Abstract 10.1897/07-032.1.abs Exposure to arsenic is known to cause
adverse effects in aquatic biota and wildlife and is of major concern
to human health. Although numerous studies have investigated the
toxicity of arsenic, little is known about the effects of acquired
tolerance on arsenic accumulation and toxicity outside of cell culture
models. Accordingly, studies were conducted on the estuarine fish,
Fundulus heteroclitus, that were preexposed to nontoxic concentrations
of arsenic (as sodium arsenite; 0.7 and 106 μmol As/L) for 96 h
or naïve to elevated arsenic to determine the effects of acclimation
on arsenic toxicity and accumulation. Tolerance to arsenic was rapidly
(96 h) acquired in killifish that were preexposed. In toxicity tests
with arsenic-acclimated killifish, preexposure to 106 μmol As/L
resulted in a reduction in toxicity when compared to näive animals.
Toxicity in arsenic-acclimated fish also was distinguished by a delayed
onset of mortality that manifested in dose-dependent fashion and
was significant even for the lower acclimation concentration (0.7
μmol As/L). The increase tolerance acquired following preexposure
to 106 μmol As/L for 96 h was associated with lower concentrations
of arsenic in all monitored tissues (e.g., gill, liver, kidney) and
the whole body when fish were exposed to 240 μmol As/L for an additional
96 h. In accordance with these observations, expression of the multidrug
resistance-associated protein (MRP)-2 gene, which is responsible
for transporting arsenic conjugated to glutathione out of cells,
was increased in the liver of arsenic-acclimated fish.},
issn = {1552-8618},
keywords = {Acclimation, Acquired tolerance, Arsenite, Seawater},
publisher = {Wiley Periodicals, Inc.},
url = {http://dx.doi.org/10.1897/07-032.1}
}
@ARTICLE{Shaw2011,
author = {Shaw, Kirsty J. and Birch, Christopher and Hughes, Elizabeth M. and
Jakes, Adam D. and Greenman, John and Haswell, Stephen J.},
title = {Microsystems for personalized biomolecular diagnostics},
journal = {Engineering in Life Sciences},
year = {2011},
volume = {11},
pages = {121--132},
number = {2},
abstract = {Abstract The development of microfluidic methodology that can be used
in conjunction with drug screening and biomolecular diagnostics offers
a route to evidence-based personalized medical care. Ideally, all
personal diagnostics are best carried out in a rapid and frequent
manner and a microfluidic interface can provide appropriate methodology.
The ability to perform genetic analysis or biomarker detection at
point-of-care would allow the clinician to decide on the most informed
course of treatment. Microfluidic systems for biomolecular analysis
at all levels, from genes to whole tissue biopsies, have been proposed.
Much of the work presented here is at an early stage of development
but will consider the range of design considerations together with
the plethora of potential applications of integrated microfluidic
technology.},
doi = {10.1002/elsc.201000175},
issn = {1618-2863},
keywords = {Diagnostics, Healthcare, Integration, Microfluidics, Personalized
medicine},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elsc.201000175}
}
@ARTICLE{Shaw2009,
author = {Shaw, Patrick J. and Ditewig, Amy C. and Waring, Jeffrey F. and Liguori,
Michael J. and Blomme, Eric A. and Ganey, Patricia E. and Roth, Robert
A.},
title = {Coexposure of Mice to Trovafloxacin and Lipopolysaccharide, a Model
of Idiosyncratic Hepatotoxicity, Results in a Unique Gene Expression
Profile and Interferon Gamma-Dependent Liver Injury},
journal = {Toxicol. Sci.},
year = {2009},
volume = {107},
pages = {270--280},
number = {1},
month = jan,
abstract = {The antibiotic trovafloxacin (TVX) has caused severe idiosyncratic
hepatotoxicity in people, whereas levofloxacin (LVX) has not. Mice
cotreated with TVX and lipopolysaccharide (LPS), but not with LVX
and LPS, develop severe hepatocellular necrosis. Mice were treated
with TVX and/or LPS, and hepatic gene expression changes were measured
before liver injury using gene array. Hepatic gene expression profiles
from mice treated with TVX/LPS clustered differently from those treated
with LPS or TVX alone. Several of the probe sets expressed differently
in TVX/LPS-treated mice were involved in interferon (IFN) signaling
and the janus kinase/signal transducers and activators of transcription
(JAK/STAT) pathway. A time course of plasma concentrations of IFN-{gamma}
and interleukin (IL)-18, which directly induces IFN-{gamma} production,
revealed that both cytokines were selectively increased in TVX/LPS-treated
mice. Both IL-18-/- and IFN-{gamma}-/- mice were significantly protected
from TVX/LPS-induced liver injury. In addition, IFN-{gamma}-/- mice
had decreased plasma concentrations of tumor necrosis factor-{alpha},
IL-18, and IL-1{beta} when compared to wild-type mice. In conclusion,
the altered expression of genes involved in IFN signaling in TVX/LPS-treated
mice led to the finding that IL-18 and IFN-{gamma} play a critical
role in TVX/LPS-induced liver injury.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/107/1/270}
}
@ARTICLE{Shaw2008,
author = {Shaw, Richard J. and Hall, Gillian L. and Lowe, Derek and Liloglou,
Triantafillos and Field, John K. and Sloan, Phillip and Risk, Janet
M.},
title = {The Role of Pyrosequencing in Head and Neck Cancer Epigenetics: Correlation
of Quantitative Methylation Data With Gene Expression},
journal = {Arch Otolaryngol Head Neck Surg},
year = {2008},
volume = {134},
pages = {251--256},
number = {3},
month = mar,
abstract = {Objective To evaluate promoter methylation quantitation using recently
described pyrosequencing techniques by correlation with messenger
RNA (mRNA) expression. Design DNA was extracted from tissue samples
and was subjected to bisulphite conversion. Quantitative methylation
data for multiple CpG sites in each of 9 gene promoters were obtained
for tumors using pyrosequencing. RNA was extracted and converted
to complementary DNA, and this formed the template for relative quantitation
assays of the expression of each gene by real-time reverse transcription-polymerase
chain reaction. Setting Academic research. Patients Thirty-seven
patients with head and neck squamous cell carcinoma. Main Outcome
Measures The genes studied were P16 (OMIM 600160), cyclin A1 (OMIM
604036), RARB (OMIM 180220), E-cadherin (OMIM 192090), MGMT (OMIM
156569), STAT1 (OMIM 600555), ATM (OMIM 607585), hMLH1 (OMIM 120436),
and TIMP3 (OMIM 188826). Immunohistochemistry was also performed
for p16. Results STAT1, TIMP3, ATM, and hMLH1 promoters were essentially
unmethylated in all cases. The data for cyclin A1 (Spearman rank
correlation, {rho} = -0.53; P < .001), MGMT ({rho} = -0.53, P < .001),
and RARB ({rho} = -0.34, P =.02) showed the expected negative correlation
between levels of methylation and mRNA expression. The data relating
to E-cadherin were inconclusive. Surprisingly, P16 expression was
statistically significantly greater in those cases with higher levels
of methylation ({rho} = 0.57, P < .001), a finding at odds with assumptions
usually made in the literature relating gene promoter methylation
to reduced gene expression. The results from p16 immunohistochemistry
were in keeping with the mRNA data, but the number of positive staining
samples proved too few for statistical analysis. Conclusions These
data present a novel perspective on head and neck cancer epigenetics
and reveal new and some unexpected associations and findings. The
advantages of pyrosequencing over nonquantitative techniques are
discussed in analyses of this nature.},
url = {http://archotol.ama-assn.org/cgi/content/abstract/134/3/251}
}
@ARTICLE{Shaykhiev2009,
author = {Shaykhiev, Renat and Krause, Anja and Salit, Jacqueline and Strulovici-Barel,
Yael and Harvey, Ben-Gary and O'Connor, Timothy P. and Crystal, Ronald
G.},
title = {Smoking-Dependent Reprogramming of Alveolar Macrophage Polarization:
Implication for Pathogenesis of Chronic Obstructive Pulmonary Disease},
journal = {J. Immunol.},
year = {2009},
volume = {183},
pages = {2867--2883},
number = {4},
month = aug,
abstract = {When exposed to a specific microenvironment, macrophages acquire either
M1- or M2-polarized phenotypes associated with inflammation and tissue
remodeling, respectively. Alveolar macrophages (AM) directly interact
with environmental stimuli such as cigarette smoke, the major risk
factor for chronic obstructive pulmonary disease (COPD), a disease
characterized by lung inflammation and remodeling. Transcriptional
profiling of AM obtained by bronchoalveolar lavage of 24 healthy
nonsmokers, 34 healthy smokers, and 12 COPD smokers was performed
to test the hypothesis whether smoking alters AM polarization, resulting
in a disease-relevant activation phenotype. The analysis revealed
that AM of healthy smokers exhibited a unique polarization pattern
characterized by substantial suppression of M1-related inflammatory/immune
genes and induction of genes associated with various M2-polarization
programs relevant to tissue remodeling and immunoregulation. Such
reciprocal changes progressed with the development of COPD, with
M1-related gene expression being most dramatically down-regulated
(p < 0.0001 vs healthy nonsmokers, p < 0.002 vs healthy smokers).
Results were confirmed with TaqMan real-time PCR and flow cytometry.
Among progressively down-regulated M1-related genes were those encoding
type I chemokines CXCL9, CXCL10, CXCL11, and CCL5. Progressive activation
of M2-related program was characterized by induction of tissue remodeling
and immunoregulatory genes such as matrix metalloproteinase (MMP)2,
MMP7, and adenosine A3 receptor (ADORA3). Principal component analysis
revealed that differential expression of polarization-related genes
has substantial contribution to global AM phenotypes associated with
smoking and COPD. In summary, the data provide transcriptome-based
evidence that AM likely contribute to COPD pathogenesis in a noninflammatory
manner due to their smoking-induced reprogramming toward M1-deactivated,
partially M2-polarized macrophages.},
url = {http://www.jimmunol.org/cgi/content/abstract/183/4/2867}
}
@ARTICLE{She2011,
author = {She, Pengxiang and Zhang, Zhiyou and Marchionini, Deanna and Diaz,
William C. and Jetton, Thomas J. and Kimball, Scot R. and Vary, Thomas
C. and Lang, Charles H. and Lynch, Christopher J.},
title = {Molecular characterization of skeletal muscle atrophy in the R6/2
mouse model of Huntington's disease},
journal = {Am J Physiol Endocrinol Metab},
year = {2011},
volume = {301},
pages = {E49-61},
number = {1},
abstract = {Huntington's disease (HD), a neurodegenerative disorder caused by
mutant huntingtin, is characterized by a catabolic phenotype. To
determine the mechanisms underlying muscle wasting, we examined key
signal transduction pathways governing muscle protein metabolism,
apoptosis, and autophagy in R6/2 mice, a well-characterized transgenic
model of HD. R6/2 mice exhibited increased adiposity, elevated energy
expenditure, and decreased body weight and lean mass without altered
food intake. Severe skeletal muscle wasting accounted for a majority
of the weight loss. Protein synthesis was unexpectedly increased
19% in gastrocnemius muscle, which was associated with overactivation
of basal and refeeding-stimulated mammalian target of rapamycin (mTOR)
signaling, elevated Akt expression and Ser473 phosphorylation, and
decreased AMPK Thr172 phosphorylation. Moreover, mRNA abundance of
atrogenes muscle ring finger-1 and atrophy F-box, was markedly attenuated
during fasting and refeeding, and the urinary excretion of 3-methylhistidine
was decreased, arguing against a role for the ubiquitin proteasome-mediated
proteolysis in the atrophy. In contrast, mRNA expression of several
caspase genes and genes involved in the extrinsic or intrinsic apoptotic
pathway, caspase-3/7, -8, and -9 activity, protein abundance of caspase-3
and -9, Fas, and Fadd, and cytochrome c release were elevated. Protein
expressions of LC3B-I and -II, beclin-I, and atg5 and -7 in muscle
were upregulated. Thus, mutant huntingtin in skeletal muscle results
in increased protein synthesis and mTOR signaling, which is countered
by activation of the apoptotic and autophagic pathways, contributing
to an overall catabolic phenotype and the severe muscle wasting.},
doi = {10.1152/ajpendo.00630.2010},
eprint = {http://ajpendo.physiology.org/cgi/reprint/301/1/E49.pdf},
url = {http://ajpendo.physiology.org/cgi/content/abstract/301/1/E49}
}
@ARTICLE{Shea2009,
author = {Shea, Jennifer and French, Curtis R and Bishop, Jessica and Martin,
Glynn and Roebothan, Barbara and Pace, David and Fitzpatrick, Donald
and Sun, Guang},
title = {Changes in the transcriptome of abdominal subcutaneous adipose tissue
in response to short-term overfeeding in lean and obese men},
journal = {Am. J. Clinical Nutrition},
year = {2009},
volume = {89},
pages = {407--415},
number = {1},
month = jan,
abstract = {Background: Obesity is caused by the excessive accumulation of adipose
tissue as a result of a chronic energy surplus. Little is known regarding
the molecular mechanisms involved in the response to an energy surplus
in human adipose tissue at the genomic level. Objective: The objective
was to investigate changes in the transcriptome of abdominal subcutaneous
adipose tissue after a positive energy challenge induced by overfeeding
in both lean and obese subjects to identify novel obesity candidate
genes. Design: A total of 26 men were recruited and classified on
the basis of percentage body fat (measured by dual-energy X-ray absorptiometry)
as lean (<20%) or obese (>25%) to participate in the baseline comparison.
Sixteen men participated in the overfeeding study (8 lean and 8 obese).
Adipose tissue biopsy samples were collected from all subjects at
the subumbilical region. Global gene expression profiles were determined
at baseline and after a 7-d hypercaloric diet at 40% above normal
energy requirements by using whole human genome DNA microarrays.
Results: Overfeeding induced differential expression in 45 genes.
Six genes displayed a significant interaction effect between adiposity
status and overfeeding treatment, including transferrin (TF), stearoyl-CoA
desaturase (SCD), transaldolase 1 (TALDO1), cathepsin C (CTSC), insulin
receptor substrate 2 (IRS2), and pyruvate dehydrogenase kinase, isozyme
4 (PDK4). Overfeeding resulted in changes in expression of these
genes in lean subjects, whereas no significant changes were evident
in obese subjects. Conclusions: Differential expression of these
6 genes may represent a protective mechanism at the molecular level
in lean subjects in response to an energy surplus. These genes represent
valuable candidates for downstream studies related to obesity.},
url = {http://www.ajcn.org/cgi/content/abstract/89/1/407}
}
@ARTICLE{Shea2011,
author = {Shea, Patrick R. and Beres, Stephen B. and Flores, Anthony R. and
Ewbank, Amy L. and Gonzalez-Lugo, Javier H. and Martagon-Rosado,
Alexandro J. and Martinez-Gutierrez, Juan C. and Rehman, Hina A.
and Serrano-Gonzalez, Monica and Fittipaldi, Nahuel and Ayers, Stephen
D. and Webb, Paul and Willey, Barbara M. and Low, Donald E. and Musser,
James M.},
title = {Distinct signatures of diversifying selection revealed by genome
analysis of respiratory tract and invasive bacterial populations},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {5039-5044},
number = {12},
abstract = {Many pathogens colonize different anatomical sites, but the selective
pressures contributing to survival in the diverse niches are poorly
understood. Group A Streptococcus (GAS) is a human-adapted bacterium
that causes a range of infections. Much effort has been expended
to dissect the molecular basis of invasive (sterile-site) infections,
but little is known about the genomes of strains causing pharyngitis
(streptococcal "sore throat"). Additionally, there is essentially
nothing known about the genetic relationships between populations
of invasive and pharyngitis strains. In particular, it is unclear
if invasive strains represent a distinct genetic subpopulation of
strains that cause pharyngitis. We compared the genomes of 86 serotype
M3 GAS pharyngitis strains with those of 215 invasive M3 strains
from the same geographical location. The pharyngitis and invasive
groups were highly related to each other and had virtually identical
phylogenetic structures, indicating they belong to the same genetic
pool. Despite the overall high degree of genetic similarity, we discovered
that strains from different host environments (i.e., throat, normally
sterile sites) have distinct patterns of diversifying selection at
the nucleotide level. In particular, the pattern of polymorphisms
in the hyaluronic acid capsule synthesis operon was especially different
between the two strain populations. This finding was mirrored by
data obtained from full-genome analysis of strains sequentially cultured
from nonhuman primates. Our results answer the long-standing question
of the genetic relationship between GAS pharyngitis and invasive
strains. The data provide previously undescribed information about
the evolutionary history of pathogenic microbes that cause disease
in different anatomical sites.},
doi = {10.1073/pnas.1016282108},
eprint = {http://www.pnas.org/cgi/reprint/108/12/5039.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/12/5039}
}
@ARTICLE{Sheader2006,
author = {Sheader, Derek L. and Williams, Timothy D. and Lyons, Brett P. and
Chipman, J. Kevin},
title = {Oxidative stress response of European flounder (Platichthys flesus)
to cadmium determined by a custom cDNA microarray},
journal = {Marine Environmental Research},
year = {2006},
volume = {62},
pages = {33--44},
number = {1},
month = jul,
abstract = {The monitoring of the impact of chemical pollutants upon marine ecosystems
commonly employs a multi-biomarker approach. Functional genomics,
using cDNA microarrays, allows for a comprehensive view of how an
organism is responding to an exposure, with respect to changes in
gene expression. Differentially expressed mRNAs were first isolated
from livers of European flounder by means of suppressive, subtractive
hybridisation. A clone set containing a total of 284 different potentially
differentially expressed mRNAs was produced, of which 84 were tentatively
identified. These were combined with previously cloned known stress
genes isolated by degenerate PCR to produce a custom 500-clone microarray
platform with each clone arrayed to four spots. Subsequent array
experiments using cadmium-treated flounder detected up-regulation
of 27 transcripts, including Cu/Zn superoxide dismutase, thioredoxin,
a peroxiredoxin and a glutathione-S-transferase, reflecting oxidative
stress in exposed flounder, while CYP1A expression was down-regulated.
These changes were confirmed by real-time PCR. The array experiment
highlighted a number of candidate genes for further analysis as potential
novel biomarkers of cadmium exposure and demonstrated the applicability
of the custom microarray approach in the study of the effects of
toxicants.},
issn = {0141-1136},
keywords = {Flounder, Microarray, Cadmium, Oxidative stress, CYP1A, Heavy metals,
Biomarker, Fish, Platichthys flesus},
url = {http://www.sciencedirect.com/science/article/B6V7H-4JF94XM-1/2/720a8d0fd5de92ed845f6f90938aa4ff}
}
@ARTICLE{Sheahan2007,
author = {Sheahan, Sharon and Bellamy, Christopher and Dunbar, Donald and Harrison,
David and Prost, Sandrine},
title = {Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte
sensitivity to TGFß cell cycle arrest},
journal = {BMC Cancer},
year = {2007},
volume = {7},
pages = {215},
number = {1},
abstract = {BACKGROUND:TGFß is critical to control hepatocyte proliferation by
inducing G1-growth arrest through multiple pathways leading to inhibition
of E2F transcription activity. The retinoblastoma protein pRb is
a key controller of E2F activity and G1/S transition which can be
inhibited in viral hepatitis. It is not known whether the impairment
of pRb would alter the growth inhibitory potential of TGFß in disease.
We asked how Rb-deficiency would affect responses to TGFß-induced
cell cycle arrest.RESULTS:Primary hepatocytes isolated from Rb-floxed
mice were infected with an adenovirus expressing CRE-recombinase
to delete the Rb gene. In control cells treatment with TGFß prevented
cells to enter S phase via decreased cMYC activity, activation of
P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes,
cMYC activity decreased slightly but P16INK4A was not activated and
the great majority of cells continued cycling. Rb is therefore central
to TGFß-induced cell cycle arrest in hepatocytes. However some Rb-null
hepatocytes remained sensitive to TGFß-induced cell cycle arrest.
As these hepatocytes expressed very high levels of P21Cip1 and P53
we investigated whether these proteins regulate pRb-independent signaling
to cell cycle arrest by evaluating the consequences of disruption
of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed
diminished growth inhibition by TGFß. Double deficiency had a similar
impact showing that in cells containing functional pRb; P21Cip and
P53 work through the same pathway to regulate G1/S in response to
TGFß. In Rb-deficient cells however, p53 but not p21Cip deficiency
had an additive effect highlighting a pRb-independent-P53-dependent
effector pathway of inhibition of E2F activity.CONCLUSION:The present
results show that otherwise genetically normal hepatocytes with disabled
p53, p21Cip1 or Rb genes respond less well to the antiproliferative
effects of TGFß. As the function of these critical cellular proteins
can be impaired by common causes of chronic liver disease and HCC,
including viral hepatitis B and C proteins, we suggest that disruption
of pRb function, and to a lesser extend P21Cip1 and P53 in hepatocytes
may represent an additional new mechanism of escape from TGFß-growth-inhibition
in the inflammatory milieu of chronic liver disease and contribute
to cancer development.},
doi = {10.1186/1471-2407-7-215},
issn = {1471-2407},
owner = {Meike Kuschel},
pubmedid = {18021445},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2407/7/215}
}
@ARTICLE{Sheedy2012,
author = {Sheedy, Donna and Say, Meichien and Stevens, Julia and Harper, Clive
G. and Kril, Jillian J.},
title = {Influence of Liver Pathology on Markers of Postmortem Brain Tissue
Quality},
journal = {Alcoholism: Clinical and Experimental Research},
year = {2012},
volume = {36},
pages = {55--60},
number = {1},
abstract = {Background:  Postmortem brain tissue provides an important resource
to investigate various brain disorders, including those resulting
from the effects of alcohol abuse. Unlike the traditionally recognized
confounders to tissue quality (e.g., coma, hypoxia), our understanding
of the effects of liver disease is incomplete. The aim of this study
was to determine the effects of liver pathology, and in particular
cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem
brain tissue quality markers, brain pH and RNA integrity.Methods: 
We measured tissue quality markers in a cohort of alcohol abuse and
control cases collected by the NSW Tissue Resource Centre. Cerebellar
tissue was used to evaluate both brain pH and RNA quality (as indicated
by the RNA integrity number: RIN). A histological assessment was
performed on each case to exclude coexisting pathologies (e.g., cerebrovascular
disease, hypoxic encephalopathy, neurodegenerative disease) and to
assess the presence or absence of HE. Autopsy reports were reviewed
for liver pathology and toxicology.Results:  Analysis revealed
that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46
(±0.3) as compared with the control mean 6.64 (±0.2). The mean
RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66
(±0.5). The severity of liver pathology affected both brain pH (p < 0.0001)
and RIN (p < 0.0001). The comparison between cirrhotic cases highlighted
increased degradation of RNA in cases with cirrhosis resulting in
HE (p = 0.0095). A similar effect was seen on brain pH (p = 0.0019).Conclusions: 
The results show that the presence of cirrhosis and, more so, HE
reduces the pH and RIN of postmortem brain tissue.},
doi = {10.1111/j.1530-0277.2011.01580.x},
issn = {1530-0277},
keywords = {Postmortem Brain, Cirrhosis, Hepatic Encephalopathy, Alcohol},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1530-0277.2011.01580.x}
}
@ARTICLE{Sheerin2011,
author = {Sheerin, Angela N. and Smith, S. Kaye and Jennert-Burston, Katrin
and Brook, Amy J. and Allen, Marcus C. and Ibrahim, Badr and Jones,
Dawn and Wallis, Corrin and Engelmann, Katrin and Rhys-Williams,
William and Faragher, Richard G. A. and Kipling, David},
title = {Characterization of cellular senescence mechanisms in human corneal
endothelial cells},
journal = {Aging Cell},
year = {2011},
pages = {no--no},
abstract = {The human cornea is a tri-laminar structure composed of several cell
types with substantial mitotic potential. Age-related changes in
the cornea are associated with declining visual acuity and the onset
of overt age-related corneal diseases. Corneal transplantation is
commonly used to restore vision in patients with damaged or diseased
corneas. However, the supply of donor tissue is limited, and thus
there is considerable interest in the development of tissue-engineered
alternatives. A major obstacle to these approaches is the short replicative
lifespan of primary human corneal endothelial cells (HCEC). Accordingly,
a comprehensive investigation of the signalling pathways and mechanisms
underpinning proliferative lifespan and senescence in HCEC was undertaken.
The effects of exogenous human telomerase reverse transcriptase expression,
p53 knockdown, disruption of the pRb pathway by over-expression of
CDK4 and reduced oxygen concentration on the lifespan of primary
HCEC were evaluated. We provide proof-of-principle that forced expression
of telomerase, when combined with either p53 knockdown or CDK4 over-expression,
is sufficient to produce immortalized HCEC lines. The resultant cell
lines express an HCEC-specific transcriptional fingerprint, and retain
expression of the corneal endothelial temperature-sensitive potassium
channel, suggesting that significant dedifferentiation does not occur
as a result of these modes of immortalization. Exploiting these insights
into proliferative lifespan barriers in HCEC will underpin the development
of novel strategies for cell-based therapies in the human cornea.},
doi = {10.1111/j.1474-9726.2011.00776.x},
issn = {1474-9726},
keywords = {senescence, telomeres, telomerase, p53, oxidative stress, CDK4, replicative
senescence},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1474-9726.2011.00776.x}
}
@ARTICLE{Shehadeh2009,
author = {Shehadeh, Lina and Mitsi, Georgia and Adi, Nikhil and Bishopric,
Nanette and Papapetropoulos, Spyridon},
title = {Expression of Lewy body protein septin 4 in postmortem brain of Parkinson's
disease and control subjects},
journal = {Mov. Disord.},
year = {2009},
volume = {24},
pages = {204--210},
number = {2},
abstract = {Abstract 10.1002/mds.22306.abs In Parkinson's disease (PD) neuronal
degeneration is associated with abnormal protein aggregation in various
forms including Lewy bodies (LBs). A major component of LBs is α-synuclein;
septin 4 (SEPT4), a polymerizing GTP-binding protein that serves
as scaffold for diverse molecules has been found to colocalize with
α-synuclein in LBs. The central role of SEPT4 in the etiopathogenesis
of PD has been suggested since SEPT4 also shows a physiological association
with α-synuclein and serves as a substrate for parkin. To this end,
we studied the expression of septin 4 and α-synuclein in postmortem
human substantia nigra (SN) and amygdala from patients with PD and
healthy controls. Twenty patients (14 men : 6 women, onset 63.0 ±
11.4 years, age 77.3 ± 7.6 years, Hoehn and Yahr 4.05/5) and 9 neurologically
healthy controls (4 men/5 women, age at death 80.1 ± 8.6 years)
were studied. Sporadic PD cases showed a statistically significant
decrease of the fold change (FC) of SNCA (FC = 0.31, P = 0.00001)
and SEPT4 (FC = 0.67, P = 0.054) gene expressions in the SN and the
amygdala (SNCA: FC = 0.49, P = 0.02; SEPT4: FC = 0.32, P = 0.007)
versus healthy controls. However, an increase of both proteins in
PD versus control subjects was observed with immunoblotting. The
semi-quantitative protein ratio calculations revealed more than 10-fold
increases for both SEPT4 and α-synuclein in PD versus control subjects.
We present for the first time similar signal expression patterns
and parallel accumulation of SEPT4 and α-synuclein in well-characterized
postmortem PD brain. Considering the heterogeneous etiology of sporadic
PD and the variability of individual human samples, SEPT4 accumulation
may be regarded as one of the common pathological changes in PD and
should therefore be further explored. © 2008 Movement Disorder Society},
issn = {1531-8257},
keywords = {alpha-synuclein, septin 4, gene expression, mRNA, protein, Parkinson's
disease, postmortem brain, substantia nigra, amygdala},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mds.22306}
}
@ARTICLE{Sheikh2012,
author = {Sheikh, Ahmad Y. and Huber, Bruno C. and Narsinh, Kazim H. and Spin,
Joshua M. and van der Bogt, Koen and de Almeida, Patricia E. and
Ransohoff, Katherine J. and Kraft, Daniel L. and Fajardo, Giovanni
and Ardigo, Diego and Ransohoff, Julia and Bernstein, Daniel and
Fischbein, Michael P. and Robbins, Robert C. and Wu, Joseph C.},
title = {In Vivo Functional and Transcriptional Profiling of Bone Marrow Stem
Cells After Transplantation Into Ischemic Myocardium},
journal = {Arterioscler Thromb Vasc Biol},
year = {2012},
volume = {32},
pages = {92-102},
number = {1},
abstract = {Objective--Clinical trials of bone marrow-derived stem cell therapy
for the heart have yielded variable results. The basic mechanism(s)
that underlies their potential efficacy remains unknown. In the present
study, we evaluated the survival kinetics, transcriptional response,
and functional outcome of intramyocardial bone marrow mononuclear
cell (BMMC) transplantation for cardiac repair in a murine myocardial
infarction model. Methods and Results--We used bioluminescence imaging
and high-throughput transcriptional profiling to evaluate the in
vivo survival kinetics and gene expression changes of transplanted
BMMCs after their engraftment into ischemic myocardium. Our results
demonstrate short-lived survival of cells following transplant, with
less than 1% of cells surviving by 6 weeks posttransplantation. Moreover,
transcriptomic analysis of BMMCs revealed nonspecific upregulation
of various cell regulatory genes, with a marked downregulation of
cell differentiation and maturation pathways. BMMC therapy caused
limited improvement of heart function as assessed by echocardiography,
invasive hemodynamics, and positron emission tomography. Histological
evaluation of cell fate further confirmed findings of the in vivo
cell tracking and transcriptomic analysis. Conclusion--Collectively,
these data suggest that BMMC therapy, in its present iteration, may
be less efficacious than once thought. Additional refinement of existing
cell delivery protocols should be considered to induce better therapeutic
efficacy.},
doi = {10.1161/ATVBAHA.111.238618},
eprint = {http://atvb.ahajournals.org/cgi/reprint/32/1/92.pdf},
url = {http://atvb.ahajournals.org/cgi/content/abstract/32/1/92}
}
@ARTICLE{ShelburneIII2009,
author = {Shelburne III, Samuel A. and Keith, David B. and Davenport, Michael
T. and Beres, Stephen B. and Carroll, Ronan K. and Musser, James
M.},
title = {Contribution of AmyA, an extracellular α-glucan degrading enzyme,
to group A streptococcal host–pathogen interaction},
journal = {Molecular Microbiology},
year = {2009},
volume = {74},
pages = {159--174},
number = {1},
abstract = {Summary α-Glucans such as starch and glycogen are abundant in the
human oropharynx, the main site of group A Streptococcus (GAS) infection.
However, the role in pathogenesis of GAS extracellular α-glucan
binding and degrading enzymes is unknown. The serotype M1 GAS genome
encodes two extracellular proteins putatively involved in α-glucan
binding and degradation; pulA encodes a cell wall anchored pullulanase
and amyA encodes a freely secreted putative cyclomaltodextrin α-glucanotransferase.
Genetic inactivation of amyA, but not pulA, abolished GAS α-glucan
degradation. The ΔamyA strain had a slower rate of translocation
across human pharyngeal epithelial cells. Consistent with this finding,
the ΔamyA strain was less virulent following mouse mucosal challenge.
Recombinant AmyA degraded α-glucans into β-cyclomaltodextrins that
reduced pharyngeal cell transepithelial resistance, providing a physiologic
explanation for the observed transepithelial migration phenotype.
Higher amyA transcript levels were present in serotype M1 GAS strains
causing invasive infection compared with strains causing pharyngitis.
GAS proliferation in a defined α-glucan-containing medium was dependent
on the presence of human salivary α-amylase. These data delineate
the molecular mechanisms by which α-glucan degradation contributes
to GAS host–pathogen interaction, including how GAS uses human
salivary α-amylase for its own metabolic benefit.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2009.06858.x}
}
@ARTICLE{ShelburneIII2011a,
author = {Shelburne III, Samuel A. and Olsen, Randall J. and Makthal, Nishanth
and Brown, Nicholas G. and Sahasrabhojane, Pranoti and Watkins, Ebru
M. and Palzkill, Timothy and Musser, James M. and Kumaraswami, Muthiah},
title = {An amino-terminal signal peptide of Vfr protein negatively influences
RopB-dependent SpeB expression and attenuates virulence in Streptococcus
pyogenes},
journal = {Molecular Microbiology},
year = {2011},
volume = {82},
pages = {1481--1495},
number = {6},
abstract = {Streptococcal pyrogenic exotoxin B (SpeB) is an extracellular cysteine
protease that is a critical virulence factor made by the major human
pathogen group A Streptococcus (GAS). speB expression is dependent
on the regulator of proteinase B (RopB) and is upregulated with increasing
cell density and during infection. Because computer modelling suggested
significant structural similarity between RopB and peptide-sensing
regulatory proteins made by other Gram-positive bacteria, we hypothesized
that speB expression is influenced by RopB–peptide interactions.
Inactivation of the gene (vfr) encoding the virulence factor related
(Vfr) protein resulted in increased speB transcript level during
the exponential growth phase, whereas provision of only the amino-terminal
region of Vfr comprising the secretion signal sequence in trans restored
a wild-type speB expression profile. Addition of the culture supernatant
from a Vfr signal peptide-expressing GAS strain restored wild-type
speB transcript level to a vfr-inactivated isogenic mutant strain.
A distinct peptide in the Vfr secretion signal sequence specifically
bound to recombinant RopB. Finally, overexpression of the Vfr secretion
signal sequence significantly decreased speB transcript level and
attenuated GAS virulence in two mouse models of invasive infection.
Taken together, these data delineate a previously unknown small peptide-mediated
regulatory system that controls GAS virulence factor production.},
doi = {10.1111/j.1365-2958.2011.07902.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2011.07902.x}
}
@ARTICLE{ShelburneIII2011,
author = {Shelburne III, Samuel A. and Sahasrobhajane, Pranoti and Suber, Bryce
and Keith, David B. and Davenport, Michael T. and Horstmann, Nicola
and Kumaraswami, Muthiah and Olsen, Randall J. and Brennan, Richard
G. and Musser, James M.},
title = {Niche-specific contribution to streptococcal virulence of a MalR-regulated
carbohydrate binding protein},
journal = {Molecular Microbiology},
year = {2011},
volume = {81},
pages = {500--514},
number = {2},
abstract = {Low G+C Gram-positive bacteria typically contain multiple LacI/GalR
regulator family members, which often have highly similar amino-terminal
DNA binding domains, suggesting significant overlap in target DNA
sequences. The LacI/GalR family regulator catabolite control protein
A (CcpA) is a global regulator of the Group A Streptococcus (GAS)
transcriptome and contributes to GAS virulence in diverse infection
sites. Herein, we studied the role of the maltose repressor (MalR),
another LacI/GalR family member, in GAS global gene expression and
virulence. MalR inactivation reduced GAS colonization of the mouse
oropharynx but did not detrimentally affect invasive infection. The
MalR transcriptome was limited to only 25 genes, and a highly conserved
MalR DNA-binding sequence was identified. Variation of the MalR binding
sequence significantly reduced MalR binding in vitro. In contrast,
CcpA bound to the same DNA sequences as MalR but tolerated variation
in the promoter sequences with minimal change in binding affinity.
Inactivation of pulA, a MalR regulated gene which encodes a cell
surface carbohydrate binding protein, significantly reduced GAS human
epithelial cell adhesion and mouse oropharyngeal colonization but
did not affect GAS invasive disease. These data delineate a molecular
mechanism by which hierarchical regulation of carbon source utilization
influences bacterial pathogenesis in a site-specific fashion.},
doi = {10.1111/j.1365-2958.2011.07708.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2011.07708.x}
}
@ARTICLE{Shelburne2008,
author = {Shelburne, Samuel A. and Keith, David B. and Davenport, Michael T.
and Horstmann, Nicola and Brennan, Richard G. and Musser, James M.},
title = {Molecular characterization of group A Streptococcus maltodextrin
catabolism and its role in pharyngitis},
journal = {Molecular Microbiology},
year = {2008},
volume = {69},
pages = {436--452},
number = {2},
abstract = {Summary We previously demonstrated that the cell-surface lipoprotein
MalE contributes to GAS maltose/maltodextrin utilization, but MalE
inactivation does not completely abrogate GAS catabolism of maltose
or maltotriose. Using a genome-wide approach, we identified the GAS
phosphotransferase system (PTS) responsible for non-MalE maltose/maltotriose
transport. This PTS is encoded by an open reading frame (M5005_spy1692)
previously annotated as ptsG based on homology with the glucose PTS
in Bacillus subtilis. Genetic inactivation of M5005_spy1692 significantly
reduced transport rates of radiolabelled maltose and maltotriose,
but not glucose, leading us to propose its reannotation as malT for
maltose transporter. The ΔmalT, ΔmalE and ΔmalE:malT strains were
significantly attenuated in their growth in human saliva and in their
ability to catabolize α-glucans digested by purified human salivary
α-amylase. Compared with wild-type, the three isogenic mutant strains
were significantly impaired in their ability to colonize the mouse
oropharynx. Finally, we discovered that the transcript levels of
maltodextrin utilization genes are regulated by competitive binding
of the maltose repressor MalR and catabolite control protein A. These
data provide novel insights into regulation of the GAS maltodextrin
genes and their role in GAS host–pathogen interaction, thereby
increasing the understanding of links between nutrient acquisition
and virulence in common human pathogens.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2008.06290.x}
}
@ARTICLE{Shelburne2008a,
author = {Shelburne, Samuel A., III and Keith, David and Horstmann, Nicola
and Sumby, Paul and Davenport, Michael T. and Graviss, Edward A.
and Brennan, Richard G. and Musser, James M.},
title = {A direct link between carbohydrate utilization and virulence in the
major human pathogen group A Streptococcus},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {1698--1703},
number = {5},
month = feb,
abstract = {Although central to pathogenesis, the molecular mechanisms used by
microbes to regulate virulence factor production in specific environments
during host-pathogen interaction are poorly defined. Several recent
ex vivo and in vivo studies have found that the level of group A
Streptococcus (GAS) virulence factor gene transcripts is temporally
related to altered expression of genes encoding carbohydrate utilization
proteins. These findings stimulated us to analyze the role in pathogenesis
of catabolite control protein A (CcpA), a GAS ortholog of a key global
regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch
as the genomewide effects of CcpA in a human pathogen are unknown,
we analyzed the transcriptome of a {Delta}ccpA isogenic mutant strain
grown in nutrient-rich medium. CcpA influences the transcript levels
of many carbohydrate utilization genes and several well characterized
GAS virulence factors, including the potent cytolysin streptolysin
S. Compared with the wild-type parental strain, the {Delta}ccpA isogenic
mutant strain was significantly less virulent in a mouse model of
invasive infection. Moreover, the isogenic mutant strain was significantly
impaired in ability to colonize the mouse oropharynx. When grown
in human saliva, a nutrient-limited environment, CcpA influenced
production of several key virulence factors not influenced during
growth in nutrient-rich medium. Purified recombinant CcpA bound to
the promoter region of the gene encoding streptolysin S. Our discovery
that GAS virulence and complex carbohydrate utilization are directly
linked through CcpA provides enhanced understanding of a mechanism
used by a Gram-positive pathogen to modulate virulence factor production
in specific environments.},
url = {http://www.pnas.org/cgi/content/abstract/105/5/1698}
}
@ARTICLE{Shelburne2007,
author = {Shelburne, Samuel A., III and Okorafor, Nnaja and Sitkiewicz, Izabela
and Sumby, Paul and Keith, David and Patel, Payal and Austin, Celest
and Graviss, Edward A. and Musser, James M.},
title = {Regulation of Polysaccharide Utilization Contributes to the Persistence
of Group A Streptococcus in the Oropharynx},
journal = {Infect. Immun.},
year = {2007},
volume = {75},
pages = {2981--2990},
number = {6},
month = jun,
abstract = {Group A Streptococcus (GAS) genes that encode proteins putatively
involved in polysaccharide utilization show growth phase-dependent
expression in human saliva. We sought to determine whether the putative
polysaccharide transcriptional regulator MalR influences the expression
of such genes and whether MalR helps GAS infect the oropharynx. Analysis
of 32 strains of 17 distinct M protein serotypes revealed that MalR
is highly conserved across GAS strains. malR transcripts were detectable
in patients with GAS pharyngitis, and the levels increased significantly
during growth in human saliva compared to the levels during growth
in glucose-containing or nutrient-rich media. To determine if MalR
influenced the expression of polysaccharide utilization genes, we
compared the transcript levels of eight genes encoding putative polysaccharide
utilization proteins in the parental serotype M1 strain MGAS5005
and its {Delta}malR isogenic mutant derivative. The transcript levels
of all eight genes were significantly increased in the {Delta}malR
strain compared to the parental strain, especially during growth
in human saliva. Following experimental infection, the {Delta}malR
strain persistently colonized the oropharynx in significantly fewer
mice than the parental strain colonized, and the numbers of {Delta}malR
strain CFU recovered were significantly lower than the numbers of
the parental strain CFU recovered. These data led us to conclude
that MalR influences the expression of genes putatively involved
in polysaccharide utilization and that MalR contributes to the persistence
of GAS in the oropharynx.},
url = {http://iai.asm.org/cgi/content/abstract/75/6/2981}
}
@ARTICLE{Shelburne2005,
author = {Shelburne, Samuel A., III and Sumby, Paul and Sitkiewicz, Izabela
and Granville, Chanel and DeLeo, Frank R. and Musser, James M.},
title = {Central role of a bacterial two-component gene regulatory system
of previously unknown function in pathogen persistence in human saliva},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {16037--16042},
number = {44},
month = nov,
abstract = {The molecular genetic mechanisms used by bacteria to persist in humans
are poorly understood. Group A Streptococcus (GAS) causes the majority
of bacterial pharyngitis cases in humans and is prone to persistently
inhabit the upper respiratory tract. To gain information about how
GAS survives in and infects the oropharynx, we analyzed the transcriptome
of a serotype M1 strain grown in saliva. The dynamic pattern of changes
in transcripts of genes [spy0874/0875, herein named sptR and sptS
(sptR/S), for saliva persistence] encoding a two-component gene regulatory
system of unknown function suggested that SptR/S contributed to persistence
of GAS in saliva. Consistent with this idea, an isogenic nonpolar
mutant strain ({Delta}sptR) was dramatically less able to survive
in saliva compared with the parental strain. Iterative expression
microarray analysis of bacteria grown in saliva revealed that transcripts
of several known and putative GAS virulence factor genes were decreased
significantly in the {Delta}sptR mutant strain. Compared with the
parental strain, the isogenic mutant strain also had altered transcripts
of multiple genes encoding proteins involved in complex carbohydrate
acquisition and utilization pathways. Western immunoblot analysis
and real-time PCR analysis of GAS in throat swabs taken from humans
with pharyngitis confirmed the findings. We conclude that SptR/S
optimizes persistence of GAS in human saliva, apparently by strategically
influencing metabolic pathways and virulence factor production. The
discovery of a genetic program that significantly increased persistence
of a major human pathogen in saliva enhances understanding of how
bacteria survive in the host and suggests new therapeutic strategies.},
url = {http://www.pnas.org/cgi/content/abstract/102/44/16037}
}
@ARTICLE{Shelburne2006,
author = {Shelburne, Samuel A., III and Sumby, Paul and Sitkiewicz, Izabela
and Okorafor, Nnaja and Granville, Chanel and Patel, Payal and Voyich,
Jovanka and Hull, Richard and DeLeo, Frank R. and Musser, James M.},
title = {Maltodextrin Utilization Plays a Key Role in the Ability of Group
A Streptococcus To Colonize the Oropharynx},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {4605--4614},
number = {8},
month = aug,
abstract = {Analysis of multiple group A Streptococcus (GAS) genomes shows that
genes encoding proteins involved in carbohydrate utilization comprise
some 15% of the core GAS genome. Yet there is a limited understanding
of how carbohydrate utilization contributes to GAS pathogenesis.
Previous genome-wide GAS studies led us to a focused investigation
of MalE, a putative maltodextrin-binding protein. Analysis of 28
strains of 22 distinct M protein serotypes showed that MalE is highly
conserved among diverse GAS strains. malE transcript levels were
significantly increased during growth in human saliva compared to
growth in a chemically defined glucose-containing medium or a nutrient-rich
medium. MalE was accessible to antibody binding, indicating that
it is expressed on the GAS cell surface. Moreover, growth in human
saliva appeared to increase MalE surface expression compared to growth
in a nutrient-rich medium. Analysis of a {Delta}malE isogenic mutant
strain revealed decreased growth in human saliva compared to wild-type
GAS. Radiolabeled carbohydrate binding assays showed that MalE was
required for the binding of maltose but not glucose. The {Delta}malE
isogenic mutant strain colonized a lower percentage of GAS-challenged
mice compared to wild-type and genetically complemented strains.
Furthermore, decreased numbers of CFU were recovered from mice infected
with the {Delta}malE strain compared to those infected with wild-type
GAS. These data demonstrate that maltodextrin acquisition is likely
to be a key factor in the ability of GAS to successfully infect the
oropharynx. Further investigation into carbohydrate transport and
metabolism pathways may yield novel insights into GAS pathogenesis.},
url = {http://iai.asm.org/cgi/content/abstract/74/8/4605}
}
@ARTICLE{Shelby2009,
author = {Shelby, Kent S. and Popham, Holly J.R.},
title = {Analysis of ESTs generated from immune-stimulated hemocytes of larval
Heliothis virescens},
journal = {Journal of Invertebrate Pathology},
year = {2009},
volume = {101},
pages = {86--95},
number = {2},
month = jun,
abstract = {Heliothis virescens immunome components responding to baculoviral
and bacterial infection were identified from expressed sequence tags
(ESTs) generated from an immune-stimulated larval hemocyte cDNA library.
A total of 5548 ESTs were generated comprising 448 contigs and 1114
singletons, totaling 1606 putative transcripts 1101 of which had
BLAST scores, including many known orthologs from other insect species.
Orthologs of known or putative immune function were identified among
them melanization pathway components, proteases, antibacterial proteins,
lectins, bacteria-binding proteins, ferritins, scavenger receptors,
cell surface receptors, signaling pathway components, and stress
response enzymes. Additionally, many enzymes of central metabolism,
cytoskeletal, mitochondrial, and ribosomal components, as well as
transcriptional and translational regulators were identified. The
effect of bacterial and baculoviral infection upon transcript levels
of three identified immunome targets from among the ESTs was quantitated
using real time PCR. Scolexin-B, C-type lectin and growth-blocking
peptide binding protein transcripts were significantly elevated by
bacterial infection. Per os infection with the baculovirus Helicoverpa
zea single nucleopolyhedrovirus however did not significantly alter
transcript levels of these three genes. The ESTs reported here are
the first large scale report of the H. virescens immunome responding
to entomopathogens, and represent a first step to a more complete
transcriptome for this pest moth.},
issn = {0022-2011},
keywords = {Expressed sequence tag, Baculovirus, Helicoverpa zea single nucleopolyhedrovirus,
Bacteria, Selenium, Budworm, Hemocyte, Scolexin-B, C-type lectin,
Growth-blocking peptide binding protein},
url = {http://www.sciencedirect.com/science/article/B6WJV-4W8VW85-1/2/628d25fa4fb112cb58cad7c5bae66f60}
}
@ARTICLE{Sheldon2011,
author = {Sheldon, Elizabeth and Vo, Kim Chi and McIntire, Ramsey A. and Aghajanova,
Lusine and Zelenko, Zara and Irwin, Juan C. and Giudice, Linda C.},
title = {Biobanking human endometrial tissue and blood specimens: standard
operating procedure and importance to reproductive biology research
and diagnostic development},
journal = {Fertility and Sterility},
year = {2011},
volume = {95},
pages = {2120--2122.e12},
number = {6},
month = may,
abstract = {Objective To develop a standard operating procedure (SOP) for collection,
transport, storage of human endometrial tissue and blood samples,
subject and specimen annotation, and establishing sample priorities.Design
The SOP synthesizes sound scientific procedures, the literature on
ischemia research, sample collection and gene expression profiling,
good laboratory practices, and the authors' experience of workflow
and sample quality.Setting The National Institutes of Health, University
of California, San Francisco, Human Endometrial Tissue and DNA Bank.Patient(s)
Women undergoing endometrial biopsy or hysterectomy for nonmalignant
indications.Intervention(s) Collecting, processing, storing, distributing
endometrial tissue and blood samples under approved institutional
review board protocols and written informed consent from participating
subjects.Main Outcome Measure(s) Standard operating procedure.Result(s)
The SOP addresses rigorous and consistent subject annotation, specimen
processing and characterization, strict regulatory compliance, and
a reference for researchers to track collection and storage times
that may influence their research.Conclusion(s) The comprehensive
and systematic approach to the procurement of human blood and endometrial
tissue in this SOP ensures the high quality, reliability, and scientific
usefulness of biospecimens made available to investigators by the
National Institutes of Health, University of California, San Francisco,
Human Endometrial Tissue and DNA Bank. The detail and perspective
in this SOP also provides a blueprint for implementation of similar
collection programs at other institutions.},
issn = {0015-0282},
keywords = {Endometrium, biobanking, standard operating procedure},
url = {http://www.sciencedirect.com/science/article/pii/S0015028211002433}
}
@ARTICLE{Shell2007,
author = {Shell, Scott and Park, Sun-Mi and Radjabi, Amir Reza and Schickel,
Robert and Kistner, Emily O. and Jewell, David A. and Feig, Christine
and Lengyel, Ernst and Peter, Marcus E.},
title = {Let-7 expression defines two differentiation stages of cancer},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {11400--11405},
number = {27},
month = jul,
abstract = {The early phases of carcinogenesis resemble embryonic development,
often involving the reexpression of embryonic mesenchymal genes.
The NCI60 panel of human tumor cell lines can genetically be subdivided
into two superclusters (SCs) that correspond to CD95 Type I and II
cells. SC1 cells are characterized by a mesenchymal and SC2 cells
by an epithelial gene signature, suggesting that SC1 cells represent
less differentiated, advanced stages of cancer. miRNAs are small
20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression
at the posttranscriptional level. By performing miRNA expression
analysis on 10 Type I and 10 Type II cells, we have determined that
SC1 cells express low and SC2 cells high levels of the miRNA let-7,
respectively, suggesting that let-7 is a marker for less advanced
cancers. Expression of the let-7 target high-mobility group A2 (HMGA2),
an early embryonic gene, but not of classical epithelial or mesenchymal
markers such as E-cadherin or vimentin, inversely correlated with
let-7 expression in SC1 and SC2 cells. Using ovarian cancer as a
model, we demonstrate that expression of let-7 and HMGA2 is a better
predictor of prognosis than classical markers such as E-cadherin,
vimentin, and Snail. These data identify loss of let-7 expression
as a marker for less differentiated cancer.},
url = {http://www.pnas.org/cgi/content/abstract/104/27/11400}
}
@ARTICLE{Shen2010,
author = {Shen, Duan and Kiehl, Thomas R. and Khattak, Sarwat F. and Li, Zheng
Jian and He, Aiqing and Kayne, Paul S. and Patel, Vishal and Neuhaus,
Isaac M. and Sharfstein, Susan T.},
title = {Transcriptomic responses to sodium chloride-induced osmotic stress:
A study of industrial fed-batch CHO cell cultures},
journal = {Biotechnol Progress},
year = {2010},
volume = {26},
pages = {1104--1115},
number = {4},
abstract = {Abstract 10.1002/btpr.398.abs The rapidly expanding market for monoclonal
antibody and Fc-fusion-protein therapeutics has increased interest
in improving the productivity of mammalian cell lines, both to alleviate
capacity limitations and control the cost of goods. In this study,
we evaluated the responses of an industrial CHO cell line producing
an Fc-fusion-protein to hyperosmotic stress, a well-known productivity
enhancer, and compared them with our previous studies of murine hybridomas
(Shen and Sharfstein, Biotechnol Bioeng. 2006;93:132–145). In batch
culture studies, cells showed substantially increased specific productivity
in response to increased osmolarity as well as significant metabolic
changes. However, the final titer showed no substantial increase
due to the decrease in viable cell density. In fed batch cultures,
hyperosmolarity slightly repressed the cellular growth rate, but
no significant change in productivity or final titer was detected.
To understand the transcriptional responses to increased osmolarity
and relate changes in gene expression to increased productivity and
repressed growth, proprietary CHO microarrays were used to monitor
the transcription profile changes in response to osmotic stress.
A set of osmotically regulated genes was generated and classified
by extracting their annotations and functionalities from online databases.
The gene list was compared with results previously obtained from
similar studies of murine-hybridoma cells. The overall transcriptomic
responses of the two cell lines were rather different, although many
functional groups were commonly perturbed between them. Building
on this study, we anticipate that further analysis will establish
connections between productivity and the expression of specific gene(s),
thus allowing rational engineering of mammalian cells for higher
recombinant-protein productivity. © 2010 American Institute of Chemical
Engineers Biotechnol. Prog., 2010},
issn = {1520-6033},
keywords = {hybridoma, Chinese hamster ovary cell, microarray, transcriptome,
osmotic stress},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/btpr.398}
}
@ARTICLE{Shen2006,
author = {Shen, Duan and Sharfstein, Susan T.},
title = {Genome-wide analysis of the transcriptional response of murine hybridomas
to osmotic shock},
journal = {Biotechnol. Bioeng.},
year = {2006},
volume = {93},
pages = {132--145},
number = {1},
abstract = {Abstract 10.1002/bit.20691.abs Hyperosmotic stress has been shown
to increase specific antibody productivity in murine hybridoma systems;
however, the mechanisms underlying this phenomenon are still poorly
understood. To elucidate the mechanisms for this phenomenon as well
as other physiological changes that occur in response to hyperosmotic
stress, we performed a genome-wide analysis of the transcriptional
response of murine hybridoma OKT3 toward hyperosmotic stress using
DNA microarrays. GeneChip® MOE430A from Affymetrix was used to determine
the differences in transcription patterns between OKT3 in hyperosmotic
culture (∼100 mOsm above control) and control culture. The chip
contains 22,690 probe sets for over 14,000 known genes and more than
4,000 ESTs. Signals were normalized using the GC-RMA algorithm and
the effectiveness of hyperosmotic stress in altering the expression
of each gene was evaluated using one-way ANOVA. 2,793 probe sets
on the chip were differentially expressed with a P < 0.05. Among
them, 349 probe sets exhibited a two-fold or greater change (with
202 up-regulated and 147 down-regulated) at one or more time points.
Within the 215 characterized, differentially expressed genes, many
are involved in metabolism/catabolism (19 induced, 12 repressed),
cell-cycle regulation (10 induced, 5 repressed) and apoptosis (8
induced, 2 repressed), regulation of transcription (18 induced, 13
repressed) and translation (2 induced, 2 repressed), transport and
signaling pathways (24 induced, 12 repressed). Surprisingly, there
were very few changes within the stress-response genes. Interestingly,
the transcription levels of both the immunoglobulin kappa and lambda
light chains showed a significant change in response to hyperosmotic
stress, although there is no detectable lambda chain in the immunoglobulin
produced in this cell line. Quantitative PCR assays with TaqMan®
probes were applied to selected genes to validate the results obtained
from microarray analysis. © 2005 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {hybridoma, microarray, transcriptome, immunoglobulin, quantitative
PCR},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.20691}
}
@ARTICLE{Shen2010a,
author = {Shen, Ding-Wu and Ma, Jichun and Okabe, Mitsunori and Zhang, Guofeng
and Xia, Di and Gottesman, Michael M.},
title = {Elevated expression of TMEM205, a hypothetical membrane protein,
is associated with cisplatin resistance},
journal = {J. Cell. Physiol.},
year = {2010},
volume = {225},
pages = {822--828},
number = {3},
abstract = {Abstract Development of cisplatin resistance in cancer cells appears
to be a consequence of multiple epigenetic alterations in genes involved
in DNA damage repair, proto-oncogenes, apoptosis, transporters, transcription
factors, etc. In this study, we found that expression of the hypothetical
transmembrane protein TMEM205 (previously known as MBC3205) is associated
with cisplatin resistance. TMEM205 was first detected by functional
cloning from a retroviral cDNA library made from human cisplatin-resistant
(CP-r) cells. TMEM205 is predicted to be a transmembrane protein,
but its expression, localization, and function have not previously
been investigated. A polyclonal antibody directed to the TMEM205
protein was raised in our laboratory. Using this antibody, it was
demonstrated that this protein is located at the cell surface. Its
expression is increased in our cisplatin-selected CP-r cell lines,
as demonstrated by immunoblotting, confocal examination, and immuno-electron
microscopy. Stable transfection of the TMEM205 gene confers resistance
to cisplatin by approximately 2.5-fold. Uptake assays with Alexa
Fluor-cisplatin showed reduced accumulation in CP-r KB-CP.3 and KB-CP.5
cells, and in TMEM205-transfected cells. Analysis of TMEM205 expression
profiles in normal human tissues indicates a differential expression
pattern with higher expression levels in the liver, pancreas, and
adrenal glands. These results indicate that a novel mechanism for
cisplatin resistance is mediated by TMEM205, and also suggest that
overexpression of TMEM205 in CP-r cells may be valuable as a biomarker
or target in cancer chemotherapy. J. Cell. Physiol. 225: 822–828,
2010. © 2010 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22287}
}
@ARTICLE{Shen2012,
author = {Shen, Hui and He, Xianzhi and Poovaiah, Charleson R. and Wuddineh,
Wegi A. and Ma, Junying and Mann, David G. J. and Wang, Huanzhong
and Jackson, Lisa and Tang, Yuhong and Neal Stewart, C. and Chen,
Fang and Dixon, Richard A.},
title = {Functional characterization of the switchgrass (Panicum virgatum)
R2R3-MYB transcription factor PvMYB4 for improvement of lignocellulosic
feedstocks},
journal = {New Phytologist},
year = {2012},
volume = {193},
pages = {121--136},
number = {1},
abstract = {* •The major obstacle for bioenergy production from switchgrass
biomass is the low saccharification efficiency caused by cell wall
recalcitrance. Saccharification efficiency is negatively correlated
with both lignin content and cell wall ester-linked p-coumarate:
ferulate (p-CAÂ :Â FA) ratio. In this study, we cloned and functionally
characterized an R2R3-MYB transcription factor from switchgrass and
evaluated its potential for developing lignocellulosic feedstocks.
* •The switchgrass PvMYB4 cDNAs were cloned and expressed in Escherichia
coli, yeast, tobacco and switchgrass for functional characterization.
Analyses included determination of phylogenetic relations, in situ
hybridization, electrophoretic mobility shift assays to determine
binding sites in target promoters, and protoplast transactivation
assays to demonstrate domains active on target promoters. * •PvMYB4
binds to the AC-I, AC-II and AC-III elements of monolignol pathway
genes and down-regulates these genes in vivo. Ectopic overexpression
of PvMYB4 in transgenic switchgrass resulted in reduced lignin content
and ester-linked p-CAÂ :Â FA ratio, reduced plant stature, increased
tillering and an approx. threefold increase in sugar release efficiency
from cell wall residues. * •We describe an alternative strategy
for reducing recalcitrance in switchgrass by manipulating the expression
of a key transcription factor instead of a lignin biosynthetic gene.
PvMYB4-OX transgenic switchgrass lines can be used as potential germplasm
for improvement of lignocellulosic feedstocks and provide a platform
for further understanding gene regulatory networks underlying switchgrass
cell wall recalcitrance.},
doi = {10.1111/j.1469-8137.2011.03922.x},
issn = {1469-8137},
keywords = {bioethanol, cell wall recalcitrance, lignin, MYB transcription factor,
transgenic switchgrass},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2011.03922.x}
}
@ARTICLE{Shen2008,
author = {Shen, H-C Jennifer and Rosen, Jennifer E and Yang, Lauren M and Savage,
Sharon A and Burns, A Lee and Mateo, Carmen M and Agarwal, Sunita
K and Chandrasekharappa, Settara C and Spiegel, Allen M and Collins,
Francis S and Marx, Stephen J and Libutti, Steven K},
title = {Parathyroid tumor development involves deregulation of homeobox genes},
journal = {Endocr. Relat. Cancer},
year = {2008},
volume = {15},
pages = {267--275},
number = {1},
month = mar,
abstract = {Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
syndrome caused by mutations in the MEN1 tumor suppressor gene. Loss
of the functional second copy of the MEN1 gene causes individuals
to develop multiple endocrine tumors, primarily affecting the parathyroid,
pituitary, and pancreas. While it is clear that the protein encoded
by MEN1, menin, suppresses endocrine tumors, its biochemical functions
and direct downstream targets remain unclear. Recent studies have
suggested that menin may act as a scaffold protein to coordinate
gene transcription, and that menin is an oncogenic cofactor for homeobox
(HOX) gene expression in hematopoietic cancer. The role of HOX genes
in adult cell differentiation is still obscure, but growing evidence
suggests that they may play important roles in the development of
cancer. Therefore, we hypothesized that specific HOX genes were regulated
by menin in parathyroid tumor development. Utilizing quantitative
TaqMan RT-PCR, we compared expression profiles of the 39 HOX genes
in human familial MEN1 (fMEN1) parathyroid tumors and sporadic parathyroid
adenomas with normal samples. We identified a large set of 23 HOX
genes whose deregulation is specific for fMEN1 parathyroid tumors,
and only 5 HOX genes whose misexpression are specific for sporadic
parathyroid tumor development. These findings provide the first evidence
that loss of the MEN1 tumor suppressor gene is associated with deregulation
of specific HOX gene expression in the development of familial human
parathyroid tumors. Our results strongly reinforce the idea that
abnormal expression of developmental HOX genes can be critical in
human cancer progression.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/15/1/267}
}
@ARTICLE{Shen2011a,
author = {Shen, Jun and Liu, Ziling and Todd, Nevins and Zhang, Howard and
Liao, Jipei and Yu, Lei and Guarnera, Maria and Li, Ruiyun and Cai,
Ling and Zhan, Min and Jiang, Feng},
title = {Diagnosis of lung cancer in individuals with solitary pulmonary nodules
by plasma microRNA biomarkers},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {374},
number = {1},
abstract = {BACKGROUND:Making a definitive preoperative diagnosis of solitary
pulmonary nodules (SPNs) found by CT has been a clinical challenge.
We previously demonstrated that microRNAs (miRNAs) could be used
as biomarkers for lung cancer diagnosis. Here we investigate whether
plasma microRNAs are useful in identifying lung cancer among individuals
with CT-detected SPNs.METHODS:By using quantitative reverse transcriptase
PCR analysis, we first determine plasma expressions of five miRNAs
in a training set of 32 patients with malignant SPNs, 33 subjects
with benign SPNs, and 29 healthy smokers to define a panel of miRNAs
that has high diagnostic efficiency for lung cancer. We then validate
the miRNA panel in a testing set of 76 patients with malignant SPNs
and 80 patients with benign SPNs.RESULTS:In the training set, miR-21
and miR-210 display higher plasma expression levels, whereas miR-486-5p
has lower expression level in patients with malignant SPNs, as compared
to subjects with benign SPNs and healthy controls (all P [less than
or equal to] 0.001). A logistic regression model with the best prediction
was built on the basis of miR-21, miR-210, and miR-486-5p. The three
miRNAs used in combination produced the area under receiver operating
characteristic curve at 0.86 in distinguishing lung tumors from benign
SPNs with 75.00% sensitivity and 84.95% specificity. Validation of
the miRNA panel in the testing set confirms their diagnostic value
that yields significant improvement over any single one.CONCLUSIONS:The
plasma miRNAs provide potential circulating biomarkers for noninvasively
diagnosing lung cancer among individuals with SPNs, and could be
further evaluated in clinical trials.},
doi = {10.1186/1471-2407-11-374},
issn = {1471-2407},
pubmedid = {21864403},
url = {http://www.biomedcentral.com/1471-2407/11/374}
}
@ARTICLE{Shen2007,
author = {Shen, Jing and Tai, Yan-Chin and Zhou, Jianbiao and Stephen Wong,
Ching-Ho and Cheang, Pek Tan S. and Fred Wong, Wai-Shiu and Xie,
Zhigang and Khan, Matiullah and Han, Jin-Hua and Chen, Chien-Shing},
title = {Synergistic antileukemia effect of genistein and chemotherapy in
mouse xenograft model and potential mechanism through MAPK signaling},
journal = {Experimental Hematology},
year = {2007},
volume = {35},
pages = {75.e1--75.e11},
number = {1},
month = jan,
abstract = {We investigated the antiproliferative effect of genistein, and its
antileukemia effect in combination with cytosine arabinoside (ara-C)
in acute myeloid leukemia (AML). Optimal dosage of genistein as single
agent and in combination with ara-C was first determined in vitro.
Genistein demonstrated a dose- and time-dependent inhibition of cell
proliferation, induction of apoptosis, and cell-cycle arrest at G2/M
phase. Gene-expression profiles revealed mitogen-activated protein
kinase (MAPK) signaling as one of the most affected biological pathways.
Phosphatidylinositol 3 kinase, protein kinase A, protein kinase C,
MAPK kinase 4, KIT, PIM1, and transforming growth factor-[beta] receptor
1, were significantly downregulated by genistein. To test whether
genistein could augment the antiproliferation activity of ara-C,
two groups of severe combined immunodeficient mice were inoculated
with NB4 and HL-60 cells, respectively, followed by treatment with
either genistein or combination of genistein and ara-C. The combination
treatment significantly inhibited tumor growth, and improved survival
of NB4 (p = 0.0031) and HL-60 (p = 0.0007) xenograft mice. Our present
study highlighted the schedule-dependent synergistic antileukemia
effect of genistein with chemotherapy in both in vitro and in vivo
models. This novel combination could potentially be a promising regimen
for treatment of AML.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4MPCXMF-B/2/e0127226570a7da3d0af6c0af380e1c0}
}
@ARTICLE{Shen2011,
author = {Shen, Jun and Todd, Nevins W and Zhang, Howard and Yu, Lei and Lingxiao,
Xing and Mei, Yuping and Guarnera, Maria and Liao, Jipei and Chou,
Amy and Lu, Changwan Larry and Jiang, Zhengran and Fang, HongBin
and Katz, Ruth L and Jiang, Feng},
title = {Plasma microRNAs as potential biomarkers for non-small-cell lung
cancer},
journal = {Lab Invest},
year = {2011},
volume = {91},
pages = {579--587},
number = {4},
month = apr,
issn = {0023-6837},
publisher = {United States and Canadian Academy of Pathology, Inc.},
url = {http://dx.doi.org/10.1038/labinvest.2010.194}
}
@ARTICLE{Shen2005,
author = {Shen, Kai and Antalis, Patricia and Gladitz, John and Sayeed, Sameera
and Ahmed, Azad and Yu, Shujun and Hayes, Jay and Johnson, Sandra
and Dice, Bethany and Dopico, Richard and Keefe, Randy and Janto,
Benjamin and Chong, William and Goodwin, Joseph and Wadowsky, Robert
M. and Erdos, Geza and Post, J. Christopher and Ehrlich, Garth D.
and Hu, Fen Z.},
title = {Identification, Distribution, and Expression of Novel Genes in 10
Clinical Isolates of Nontypeable Haemophilus influenzae},
journal = {Infect. Immun.},
year = {2005},
volume = {73},
pages = {3479--3491},
number = {6},
month = jun,
abstract = {We hypothesize that Haemophilus influenzae, as a species, possesses
a much greater number of genes than that found in any single H. influenzae
genome. This supragenome is distributed throughout naturally occurring
infectious populations, and new strains arise through autocompetence
and autotransformation systems. The effect is that H. influenzae
populations can readily adapt to environmental stressors. The supragenome
hypothesis predicts that significant differences exist between and
among the genomes of individual infectious strains of nontypeable
H. influenzae (NTHi). To test this prediction, we obtained 10 low-passage
NTHi clinical isolates from the middle ear effusions of patients
with chronic otitis media. DNA sequencing was performed with 771
clones chosen at random from a pooled genomic library. Homology searching
demonstrated that [~]10% of these clones were novel compared to the
H. influenzae Rd KW20 genome, and most of them did not match any
DNA sequence in GenBank. Amino acid homology searches using hypothetical
translations of the open reading frames revealed homologies to a
variety of proteins, including bacterial virulence factors not previously
identified in the NTHi isolates. The distribution and expression
of 53 of these genes among the 10 strains were determined by PCR-
and reverse transcription PCR-based analyses. These unique genes
were nonuniformly distributed among the 10 isolates, and transcription
of these genes in planktonic cultures was detected in 50% (177 of
352) of the occurrences. All of the novel sequences were transcribed
in one or more of the NTHi isolates. Seventeen percent (9 of 53)
of the novel genes were identified in all 10 NTHi strains, with each
of the remaining 44 being present in only a subset of the strains.
These genic distribution analyses were more effective as a strain
discrimination tool than either multilocus sequence typing or 23S
ribosomal gene typing methods.},
url = {http://iai.asm.org/cgi/content/abstract/73/6/3479}
}
@ARTICLE{Shen2006a,
author = {Shen, Kai and Gladitz, John and Antalis, Patricia and Dice, Bethany
and Janto, Benjamin and Keefe, Randy and Hayes, Jay and Ahmed, Azad
and Dopico, Richard and Ehrlich, Nathan and Jocz, Jennifer and Kropp,
Laura and Yu, Shujun and Nistico, Laura and Greenberg, David P. and
Barbadora, Karen and Preston, Robert A. and Post, J. Christopher
and Ehrlich, Garth D. and Hu, Fen Z.},
title = {Characterization, Distribution, and Expression of Novel Genes among
Eight Clinical Isolates of Streptococcus pneumoniae},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {321--330},
number = {1},
month = jan,
abstract = {Eight low-passage-number Streptococcus pneumoniae clinical isolates,
each of a different serotype and a different multilocus sequence
type, were obtained from pediatric participants in a pneumococcal
vaccine trial. Comparative genomic analyses were performed with these
strains and two S. pneumoniae reference strains. Individual genomic
libraries were constructed for each of the eight clinical isolates,
with an average insert size of [~]1 kb. A total of 73,728 clones
were picked for arraying, providing more than four times genomic
coverage per strain. A subset of 4,793 clones were sequenced, for
which homology searches revealed that 750 (15.6%) of the sequences
were unique with respect to the TIGR4 reference genome and 263 (5.5%)
clones were unrelated to any available streptococcal sequence. Hypothetical
translations of the open reading frames identified within these novel
sequences showed homologies to a variety of proteins, including bacterial
virulence factors not previously identified in S. pneumoniae. The
distribution and expression patterns of 58 of these novel sequences
among the eight clinical isolates were analyzed by PCR- and reverse
transcriptase PCR-based analyses, respectively. These unique sequences
were nonuniformly distributed among the eight isolates, and transcription
of these genes in planktonic cultures was detected in 81% (172/212)
of their genic occurrences. All 58 novel sequences were transcribed
in one or more of the clinical strains, suggesting that they all
correspond to functional genes. Sixty-five percent (38/58) of these
sequences were found in 50% or less of the clinical strains, indicating
a significant degree of genomic plasticity among natural isolates.},
url = {http://iai.asm.org/cgi/content/abstract/74/1/321}
}
@ARTICLE{Shen2006b,
author = {Shen, Kai and Sayeed, Sameera and Antalis, Patricia and Gladitz,
John and Ahmed, Azad and Dice, Bethany and Janto, Benjamin and Dopico,
Richard and Keefe, Randy and Hayes, Jay and Johnson, Sandra and Yu,
Sujun and Ehrlich, Nathan and Jocz, Jennifer and Kropp, Laura and
Wong, Ray and Wadowsky, Robert M. and Slifkin, Malcolm and Preston,
Robert A. and Erdos, Geza and Post, J. Christopher and Ehrlich, Garth
D. and Hu, Fen Z.},
title = {Extensive Genomic Plasticity in Pseudomonas aeruginosa Revealed by
Identification and Distribution Studies of Novel Genes among Clinical
Isolates},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {5272--5283},
number = {9},
month = sep,
abstract = {The distributed genome hypothesis (DGH) states that each strain within
a bacterial species receives a unique distribution of genes from
a population-based supragenome that is many times larger than the
genome of any given strain. The observations that natural infecting
populations are often polyclonal and that most chronic bacterial
pathogens have highly developed mechanisms for horizontal gene transfer
suggested the DGH and provided the means and the mechanisms to explain
how chronic infections persist in the face of a mammalian host's
adaptive defense mechanisms. Having previously established the validity
of the DGH for obligate pathogens, we wished to evaluate its applicability
to an opportunistic bacterial pathogen. This was accomplished by
construction and analysis of a highly redundant pooled genomic library
containing approximately 216,000 functional clones that was constructed
from 12 low-passage clinical isolates of Pseudomonas aeruginosa,
6 otorrheic isolates and 6 from other body sites. Sequence analysis
of 3,214 randomly picked clones (mean insert size, [~]1.4 kb) from
this library demonstrated that 348 (10.8%) of the clones were unique
with respect to all genomic sequences of the P. aeruginosa prototype
strain, PAO1. Hypothetical translations of the open reading frames
within these unique sequences demonstrated protein homologies to
a number of bacterial virulence factors and other proteins not previously
identified in P. aeruginosa. PCR and reverse transcription-PCR-based
assays were performed to analyze the distribution and expression
patterns of a 70-open reading frame subset of these sequences among
11 of the clinical strains. These sequences were unevenly distributed
among the clinical isolates, with nearly half (34/70) of the novel
sequences being present in only one or two of the individual strains.
Expression profiling revealed that a vast majority of these sequences
are expressed, strongly suggesting they encode functional proteins.},
url = {http://iai.asm.org/cgi/content/abstract/74/9/5272}
}
@ARTICLE{Shen2009,
author = {Shen, Qin and Wang, Xusheng and Chen, Ying and Xu, Lingli and Wang,
Xiaodong and Lu, Lu},
title = {Expression QTL and regulatory network analysis of microtubule-associated
protein tau gene},
journal = {Parkinsonism \& Related Disorders},
year = {2009},
volume = {15},
pages = {525--531},
number = {7},
month = aug,
abstract = {Numerous studies have shown that the microtubule-associated protein
tau (Mapt) gene plays an important role in tauopathies. However,
little is known about the genetic regulatory network. In this study,
we combined array analysis and quantitative trait loci (QTL) mapping
approaches (genetical genomics) to characterize the expression variation
and the regulatory network of Mapt in mouse. Through examining the
probe sets for overlapping single nucleotide polymorphysms (SNPs),
two probe sets without overlapping SNPs were selected for QTL mapping.
Interval mapping results showed that expression quantitative trait
loci (eQTL) mapping for Mapt had a significant linkage score (LRS)
of 27.2. Moreover, the QTL was mapped to within 3 Mb of the location
of the gene itself (Mapt) as a cis-acting QTL. Through mapping the
joint modulation of Mapt, we identified 22 transcripts/genes with
trans-regulated QTLs close to the location of Mapt. By further excluding
the correlated transcripts due to linkage disequilibrium, the result
highlighted three genes as potential downstream genes of Mapt. Expression
correlation and genetic network analysis demonstrated that Mapt co-varies
with many tauopathies-related genes, including Gsk3b, Falz, Apbb2,
Slc1a3, Ntrk2, Pik3ca, and Ikbkap. These results demonstrate that
the genetical genomics approach provides a powerful tool for constructing
pathways that contribute to complex traits, such as neurodegenerative
disorders.},
issn = {1353-8020},
keywords = {Mapt, Expression QTL, Neurodegenerative disorders, Tau, Tauopathies,
Genetic regulatory network},
url = {http://www.sciencedirect.com/science/article/B6TB9-4VP1CT3-1/2/7a29e6655a4f23dfa5c8398a8081e83b}
}
@ARTICLE{Shenton2006,
author = {Shenton, Daniel and Smirnova, Julia B. and Selley, Julian N. and
Carroll, Kathleen and Hubbard, Simon J. and Pavitt, Graham D. and
Ashe, Mark P. and Grant, Chris M.},
title = {Global Translational Responses to Oxidative Stress Impact upon Multiple
Levels of Protein Synthesis},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {29011--29021},
number = {39},
month = sep,
abstract = {Global inhibition of protein synthesis is a common response to stress
conditions. We have analyzed the regulation of protein synthesis
in response to oxidative stress induced by exposure to H2O2 in the
yeast Saccharomyces cerevisiae. Our data show that H2O2 causes an
inhibition of translation initiation dependent on the Gcn2 protein
kinase, which phosphorylates the {alpha}-subunit of eukaryotic initiation
factor-2. Additionally, our data indicate that translation is regulated
in a Gcn2-independent manner because protein synthesis was still
inhibited in response to H2O2 in a gcn2 mutant. Polysome analysis
indicated that H2O2 causes a slower rate of ribosomal runoff, consistent
with an inhibitory effect on translation elongation or termination.
Furthermore, analysis of ribosomal transit times indicated that oxidative
stress increases the average mRNA transit time, confirming a post-initiation
inhibition of translation. Using microarray analysis of polysome-
and monosome-associated mRNA pools, we demonstrate that certain mRNAs,
including mRNAs encoding stress protective molecules, increase in
association with ribosomes following H2O2 stress. For some candidate
mRNAs, we show that a low concentration of H2O2 results in increased
protein production. In contrast, a high concentration of H2O2 promotes
polyribosome association but does not necessarily lead to increased
protein production. We suggest that these mRNAs may represent an
mRNA store that could become rapidly activated following relief of
the stress condition. In summary, oxidative stress elicits complex
translational reprogramming that is fundamental for adaptation to
the stress.},
url = {http://www.jbc.org/cgi/content/abstract/281/39/29011}
}
@ARTICLE{Shepherd2008,
author = {Shepherd, Christopher J. and Rizzo, Siân and Ledaki, Ioanna and
Davies, Melissa and Brewer, Daniel and Attard, Gerhardt and de Bono,
Johann and Hudson, David L.},
title = {Expression profiling of CD133+ and CD133— epithelial cells from
human prostate},
journal = {Prostate},
year = {2008},
volume = {68},
pages = {1007--1024},
number = {9},
abstract = {Abstract 10.1002/pros.20765.abs BACKGROUND Recent evidence suggests
that prostate stem cells in benign and tumor tissue express the cell
surface marker CD133, but these cells have not been well characterized.
The aim of our study was to gene expression profile CD133-expressing
cells. METHODS We analyzed CD133-positive (CD133+) and -negative
(CD133−) sub-populations of high-integrin expressing epithelial
cells isolated from benign human prostate tissue and hormone-refractory
prostate cancer (HRPC). RESULTS CD133+ cells freshly isolated from
benign prostate tissue exhibited an expression profile characteristic
of a putative stem/progenitor cell population, with transcripts involved
in biological processes ranging from development and ion homeostasis
to cell communication. The profile of CD133− cells was consistent
with that of a transit amplifying population, suggesting up-regulated
proliferation and metabolism. Comparison of benign populations to
those from HRPC showed some similarities between CD133+ profiles
but also revealed significant differences that provide a tumor-specific
pattern, which included evidence of increased metabolic activity
and active proliferation. Subsequently, we demonstrated protein expression
of a number of candidate genes in these cell populations and in benign
tissue. In a novel observation we also found expression of some of
these markers in prostate tumors, including the oligodendrocyte lineage
transcription factor OLIG1. CONCLUSIONS This study provides a unique
genome-wide molecular signature of CD133+ and CD133− human prostate
epithelial cells. This will provide a valuable resource for prostate
stem cell biology research and the identification of novel therapeutic
targets for the treatment of prostate cancer. Prostate 68:1007–1024,
2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {prostate, epithelial, stem cells, CD133, microarray},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20765}
}
@ARTICLE{Sher2012,
author = {Sher, Noa and Bell, George W. and Li, Sharon and Nordman, Jared and
Eng, Thomas and Eaton, Matthew L. and MacAlpine, David M. and Orr-Weaver,
Terry L.},
title = {Developmental control of gene copy number by repression of replication
initiation and fork progression},
journal = {Genome Res.},
year = {2012},
volume = {22},
pages = {64-75},
number = {1},
abstract = {Precise DNA replication is crucial for genome maintenance, yet this
process has been inherently difficult to study on a genome-wide level
in untransformed differentiated metazoan cells. To determine how
metazoan DNA replication can be repressed, we examined regions selectively
under-replicated in Drosophila polytene salivary glands, and found
they are transcriptionally silent and enriched for the repressive
H3K27me3 mark. In the first genome-wide analysis of binding of the
origin recognition complex (ORC) in a differentiated metazoan tissue,
we find that ORC binding is dramatically reduced within these large
domains, suggesting reduced initiation as one mechanism leading to
under-replication. Inhibition of replication fork progression by
the chromatin protein SUUR is an additional repression mechanism
to reduce copy number. Although repressive histone marks are removed
when SUUR is mutated and copy number restored, neither transcription
nor ORC binding is reinstated. Tethering of the SUUR protein to a
specific site is insufficient to block replication, however. These
results establish that developmental control of DNA replication,
at both the initiation and elongation stages, is a mechanism to change
gene copy number during differentiation.},
doi = {10.1101/gr.126003.111},
eprint = {http://genome.cshlp.org/cgi/reprint/22/1/64.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/22/1/64}
}
@ARTICLE{Sheridan2006,
author = {Sheridan, Carol and Sadaria, Miral and Bhat-Nakshatri, Poornima and
Goulet, Jr., Robert and Edenberg, Howard J. and McCarthy, Brian P.
and Chang, Cheong-Hee and Srour, Edward F. and Nakshatri, Harikrishna},
title = {Negative regulation of MHC class II gene expression by CXCR4},
journal = {Experimental Hematology},
year = {2006},
volume = {34},
pages = {1085--1092},
number = {8},
month = aug,
abstract = {Objective CXCR4 is overexpressed in 23 types of cancers of both hematopoietic
and nonhematopoietic origin. Based on the known role of CXCR4 and
its ligand CXCL12 in homing of hematopoietic cells, CXCR4 is likely
to play a role in metastasis. We have initiated a study aimed at
dissecting additional functions of CXCR4 in cancer cells, particularly
in relation to the immune system.Materials and Methods RNA from CXCR4+
and CXCR4- subpopulations of MDA-MB-231 breast cancer cells was subjected
to microarray analysis. Cell surface expression of CXCR4 and MHC
class II proteins were determined by flow cytometry. Real-time PCR
was used for measuring mRNA levels of MHC class II and CIITA, the
master regulator of MHC class II gene expression.Results 1988 genes
were differentially expressed (p < 0.001) between CXCR4+ and CXCR4-
cells. The expression of class II genes HLA-DP[alpha]1, HLA-DQ[beta]1,
HLA-DR[alpha], HLA-DR[beta]1, HLA-DR[beta]3, and CD74 was lower by
2.6-fold to eightfold in CXCR4+ cells compared to CXCR4- cells. Basal
and IFN-[gamma]-inducible HLA-DR mRNA and protein levels were lower
in CXCR4+ cells than in CXCR4- cells. HLA-DR mRNA expression in both
cell types was reduced by CXCL12; the ability of CXCL12 to reduce
HLA-DR was lower in cells expressing short interfering RNA against
CXCR4. PKA inhibitor H89 and the SRC kinase inhibitor PP2 increased
HLA-DR expression in CXCR4+ cells. The basal but not IFN-[gamma]-inducible
expression of CIITA was 2.5-fold higher in CXCR4- cells compared
to CXCR4+ cells. CD34+/CD38- hematopoietic cells from the human bone
marrow contain a distinct CXCR4+/HLA-DR- subpopulation of cells.Conclusion
CXCR4 may influence the immune system under physiologic and pathologic
conditions through negative regulation of MHC class II expression,
possibly through PKA and SRC kinase.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4KG44JB-H/2/1b95ac65d5e836097efaf2e766bfff67}
}
@ARTICLE{Sheridan2011,
author = {Michael P. Sheridan and John A. Browne and David E. MacHugh and Eamon
Costello and Eamonn Gormley},
title = {Impact of delayed processing of bovine peripheral blood on differential
gene expression},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
pages = { - },
number = {0},
abstract = {RT-qPCR can be used to accurately determine expression levels of genes
following RNA extraction from tissue samples. If blood is the source
of total RNA, it is often desirable to process the samples immediately
following collection because delays in processing for RNA extraction
may influence mRNA expression estimates obtained from RT-qPCR analyses.
However, this may not be feasible if the site of blood collection
is distant from the processing laboratory. In the present study,
the effects of delays in the processing of blood samples on mRNA
expression data was investigated using a panel of 23 functionally
diverse genes from five different gene ontology (GO) categories in
peripheral blood sampled from ten age-matched healthy cattle. Venous
blood was collected in Tempusâ„¢ Blood RNA tubes, which contain reagents
that lyse blood cells immediately and stabilise the RNA signature
(T0). Blood was also collected in conventional lithium heparin collection
tubes, and stored at ambient temperature for T4, T6 and T8 h,
prior to total RNA extraction. The mRNA expression profiles of these
23 genes were determined by RT-qPCR and compared across the time
course. Thirteen genes showed significant up- or down-fold changes
in mRNA expression over the 8 h time course. Among the GO categories,
genes in the Immune response category showed the most differential
expression. These results also demonstrated that the changes in mRNA
expression for the IFNG gene, which encodes the cytokine IFN-γ,
did not correspond to IFN-γ protein levels estimated using ELISA.},
doi = {10.1016/j.vetimm.2011.11.006},
issn = {0165-2427},
keywords = {mRNA stability},
url = {http://www.sciencedirect.com/science/article/pii/S016524271100451X}
}
@ARTICLE{Sherman-Baust2011,
author = {Sherman-Baust, Cheryl and Becker, Kevin and Wood, William and Zhang,
Yongqing and Morin, Patrice},
title = {Gene Expression and Pathway Analysis of Ovarian Cancer Cells Selected
for Resistance to Cisplatin, Paclitaxel, or Doxorubicin},
journal = {Journal of Ovarian Research},
year = {2011},
volume = {4},
pages = {21},
number = {1},
abstract = {BACKGROUND:Resistance to current chemotherapeutic agents is a major
cause of therapy failure in ovarian cancer patients, but the exact
mechanisms leading to the development of drug resistance remain unclear.METHODS:To
better understand mechanisms of drug resistance, and possibly identify
novel targets for therapy, we generated a series of drug resistant
ovarian cancer cell lines through repeated exposure to three chemotherapeutic
drugs (cisplatin, doxorubicin, or paclitaxel), and identified changes
in gene expression patterns using Illumina whole-genome expression
microarrays. Validation of selected genes was performed by RT-PCR
and immunoblotting. Pathway enrichment analysis using the KEGG, GO,
and Reactome databases was performed to identify pathways that may
be important in each drug resistance phenotype.RESULTS:A total of
845 genes (p<0.01) were found altered in at least one drug resistance
phenotype when compared to the parental, drug sensitive cell line.
Focusing on each resistance phenotype individually, we identified
460, 366, and 337 genes significantly altered in cells resistant
to cisplatin, doxorubicin, and paclitaxel, respectively. Of the 845
genes found altered, only 62 genes were simultaneously altered in
all three resistance phenotypes. Using pathway analysis, we found
many pathways enriched for each resistance phenotype, but some dominant
pathways emerged. The dominant pathways included signaling from the
cell surface and cell movement for cisplatin resistance, proteasome
regulation and steroid biosynthesis for doxorubicin resistance, and
control of translation and oxidative stress for paclitaxel resistance.CONCLUSIONS:Ovarian
cancer cells develop drug resistance through different pathways depending
on the drug used in the generation of chemoresistance. A better understanding
of these mechanisms may lead to the development of novel strategies
to circumvent the problem of drug resistance.},
url = {http://www.ovarianresearch.com/content/4/1/21}
}
@ARTICLE{Sherrin2009,
author = {Sherrin, T. and Blank, T. and Saravana, R. and Rayner, M. and Spiess,
J. and Todorovic, C.},
title = {Region specific gene expression profile in mouse brain after chronic
corticotropin releasing factor receptor 1 activation: the novel role
for diazepam binding inhibitor in contextual fear conditioning},
journal = {Neuroscience},
year = {2009},
volume = {162},
pages = {14--22},
number = {1},
month = aug,
issn = {0306-4522},
keywords = {CRF, priming, prefrontal cortex, hippocampus, anxiety, fear},
url = {http://www.sciencedirect.com/science/article/B6T0F-4W1JW4S-B/2/f755f0dd2d0fb7df7a4ced7b864eea6e}
}
@ARTICLE{Sherwin2008,
author = {Sherwin, J.R.A. and Sharkey, A.M. and Mihalyi, A. and Simsa, P. and
Catalano, R.D. and D'Hooghe, T.M.},
title = {Global gene analysis of late secretory phase, eutopic endometrium
does not provide the basis for a minimally invasive test of endometriosis},
journal = {Hum. Reprod.},
year = {2008},
volume = {23},
pages = {1063--1068},
number = {5},
month = may,
abstract = {BACKGROUNDEndometriosis occurs in 10% of women and is currently diagnosed
by invasive laparoscopic testing. We tested the hypothesis that endometrial
gene expression in late secretory phase endometrium differs between
patients with and without endometriosis. METHODSTen patients with
laparoscopically proven endometriosis (minimal/mild n = 5 and moderate/severe
n = 5) and six controls, underwent endometrial biopsy in the late
secretory phase (Day 23 onwards). Microarray interrogation of eutopic
endometrial gene expression was performed. RESULTSMicroarray data
were obtained for all control samples and eight samples from the
endometriosis patients (n = 4 minimal/mild, n = 4 moderate/severe
disease). Eight genes were identified as up-regulated and one gene
was down-regulated in all endometriotic samples (more than 1.75-fold,
P < 0.01). Real-time PCR analysis of protocadherin-17 (PCDH17), protein
tyrosine phosphatase, receptor type, R (PTPRR) and interleukin-6
signal transducer (IL6ST) expression validated the microarray findings.
CONCLUSIONSExpression of very few transcripts differs, in late secretory
eutopic endometrium, between controls and patients with endometriosis.
The median fold changes of these genes are small. No transcripts
were identified that could discriminate between minimal/mild and
moderate/severe endometriosis. Therefore, interrogation of the late
secretory endometrial transcriptome is not likely to form the basis
of a minimally invasive diagnostic test for endometriosis.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/23/5/1063}
}
@ARTICLE{Sherwin2010,
author = {Sherwin, J. R. A. and Hastings, J. M. and Jackson, K. S. and Mavrogianis,
P. A. and Sharkey, A. M. and Fazleabas, A. T.},
title = {The Endometrial Response to Chorionic Gonadotropin Is Blunted in
a Baboon Model of Endometriosis},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {4982--4993},
number = {10},
month = oct,
abstract = {Endometriosis-associated infertility has a multifactorial etiology.
We tested the hypothesis that the endometrial response to the early
embryonic signal, human chorionic gonadotropin (hCG), alters over
time in a nonhuman primate model of endometriosis. Animals with experimental
or spontaneous endometriosis were treated with hCG (30 IU/d), from
d 6 after ovulation for 5 d, via an oviductal cannula. Microarray
analysis of endometrial transcripts from baboons treated with hCG
at 3 and 6 months of disease (n = 6) identified 22 and 165 genes,
respectively, whose levels differed more than 2-fold compared with
disease-free (DF) animals treated with hCG (P < 0.01). Quantitative
RT-PCR confirmed abnormal responses of known hCG-regulated genes.
APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG
were up-regulated by hCG in animals with endometriosis. In contrast,
the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry
demonstrated dysregulation of C3 and superoxide dismutase 2 proteins.
We demonstrate that this abnormal response to hCG persists for up
to 15 months after disease induction and that the nature of the abnormal
response changes as the disease progresses. Immunohistochemistry
showed that this aberrant gene expression was not a consequence of
altered LH/choriogonadotropin receptor distribution in the endometrium
of animals with endometriosis. We have shown that endometriosis induces
complex changes in the response of eutopic endometrium to hCG, which
may prevent the acquisition of the full endometrial molecular repertoire
necessary for decidualization and tolerance of the fetal allograft.
This may in part explain endometriosis-associated implantation failure.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/10/4982}
}
@ARTICLE{Sherwin2007,
author = {Sherwin, J. R. A. and Sharkey, A. M. and Cameo, P. and Mavrogianis,
P. M. and Catalano, R. D. and Edassery, S. and Fazleabas, A. T.},
title = {Identification of Novel Genes Regulated by Chorionic Gonadotropin
in Baboon Endometrium during the Window of Implantation},
journal = {Endocrinology},
year = {2007},
volume = {148},
pages = {618--626},
number = {2},
month = feb,
abstract = {Chorionic gonadotropin (CG) is an early embryo-derived signal that
is known to support the corpus luteum. An in vivo baboon model was
used to study the direct actions of human CG (hCG) on the endometrium,
during the periimplantation period. Endometrial gene expression was
analyzed using microarrays. The endometrial biopsies were taken from
hCG-treated (n = 5) and control (n = 6) animals on d 10 after ovulation.
Class comparison identified 61 genes whose transcript levels differed
between control and hCG-treated samples (48 increased, 13 decreased
in mean expression level more than 2.5-fold; P < 0.01). Real-time
PCR of transcript abundance confirmed up-regulation of several of
these, including SerpinA3, matrix metalloproteinase 7, leukemia inhibitory
factor (LIF), IL-6, and Complement 3 (P [≤] 0.05). Analysis of
protein abundance in endometrial flushings showed increased LIF and
IL-6 protein in uterine flushings from hCG-treated animals compared
with controls. Complement C3 and Superoxide dismutase 2 that were
also up-regulated, were further evaluated by immunocytochemistry.
Complement C3 showed a marked increase in stromal staining in response
to hCG, whereas and superoxide dismutase 2 localization was most
markedly increased in the glandular epithelial cells. Expression
of Soluble Frizzled Related Protein 4, the most highly down-regulated
gene, was also validated by PCR. Our experiments have shown that
hCG induces alterations in the endometrial expression of genes that
regulate embryo attachment, extracellular matrix remodeling and the
modulation of the immune response around the implanting blastocyst.
Several of these genes, including LIF and gp130, have been shown
to be essential for implantation in other species. This study provides
strong evidence that the preimplantation embryo itself influences
the development of the receptive endometrium via secreted paracrine
signals.},
url = {http://endo.endojournals.org/cgi/content/abstract/148/2/618}
}
@ARTICLE{Sherwood2011b,
author = {Sherwood, Karen and Head, Mark and Walker, Robert and Smith, Colin
and Ironside, James W. and Fazakerley, John K.},
title = {A new Index of Agonal State for neurological disease},
journal = {Neuropathology and Applied Neurobiology},
year = {2011},
pages = {no--no},
doi = {10.1111/j.1365-2990.2011.01163.x},
issn = {1365-2990},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2990.2011.01163.x}
}
@ARTICLE{Sherwood2011,
author = {Sherwood, Karen R. and Head, Mark W. and Walker, Robert and Smith,
Colin and Ironside, James W. and Fazakerley, John K.},
title = {RNA integrity in post-mortem human vCJD and control brain tissue},
journal = {Neuropathology and Applied Neurobiology},
year = {2011},
pages = {no--no},
abstract = {ABSTRACT Aims: To determine pre- and post-mortem factors affecting
quality and yield of RNA isolated from the unique archived brain
material in the UK National CJD Surveillance Unit Brain and Tissue
Bank and to compare this to control brain tissue with no neurological
disease. Methods: In parallel and in replicate, RNA was prepared
from the frontal parasagittal or sub-frontal cortex of samples dissected
from half brains (frozen intact) or from brain samples snap frozen
or placed in RNALater. 350 RNA samples from 78 human autopsy cases;
21 vCJD, 26 other neurological disease (OND) and 31 non-neurological
disease (NND) were studied. Results: There was no difference in the
quality or yield of RNA isolated from vCJD, OND and NND brains. RNA
preparations from archived frozen half brains or snap frozen autopsy
samples were generally of poor quality (RIN <5). There was a highly
significant negative correlation between the number of times frozen
half brains had been sampled and the quality of RNA. Samples stored
in RNALater provided higher quality RNA (RIN >5). Age at death, gender,
post-mortem interval and freezer storage time had no effect on RNA
quality. Conclusion: Reasonable quality RNA can be isolated from
samples dissected from archived frozen human half brains but repeated
sampling results in RNA degradation. Better quality RNA is obtained
from samples placed in RNALater than from snap frozen samples. The
quality and yield of RNA are not affected by age at death, gender,
post-mortem interval of >6 hrs or freezer storage time.},
doi = {10.1111/j.1365-2990.2011.01162.x},
issn = {1365-2990},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2990.2011.01162.x}
}
@ARTICLE{Sherwood2011a,
author = {Sherwood, K. R. and Head, M. W. and Walker, R. and Smith, C. and
Ironside, J. W. and Fazakerley, J. K.},
title = {RNA integrity in post mortem human variant Creutzfeldt–Jakob disease
(vCJD) and control brain tissue},
journal = {Neuropathology and Applied Neurobiology},
year = {2011},
volume = {37},
pages = {633--642},
number = {6},
abstract = {K. R. Sherwood, M. W. Head, R. Walker, C. Smith, J. W. Ironside and
J. K. Fazakerley (2011) Neuropathology and Applied Neurobiology37,
633–642RNA integrity in post mortem human variant Creutzfeldt–Jakob
disease (vCJD) and control brain tissueAims: To determine premortem
and post mortem factors affecting quality and yield of RNA isolated
from the unique archived brain material in the UK National Creutzfeldt–Jakob
Disease Surveillance Unit Brain and Tissue Bank and to compare this
to control brain tissue with no neurological disease. Methods: In
parallel and in replicate, RNA was prepared from the frontal parasagittal
or subfrontal cortex of samples dissected from half brains (frozen
intact) or from brain samples snap frozen or placed in RNALater.
A total of 350 RNA samples from 78 human autopsy cases, 21 variant
Creutzfeldt–Jakob disease, 26 other neurological diseases and 31
non-neurological diseases were studied. Results: There was no difference
in the quality or yield of RNA isolated from variant Creutzfeldt–Jakob
disease, other neurological disease and non-neurological disease
brains. RNA preparations from archived frozen half brains or snap
frozen autopsy samples were generally of poor quality (RNA integrity
number < 5). There was a highly significant negative correlation
between the number of times frozen half brains had been sampled and
the quality of RNA. Samples stored in RNALater provided higher-quality
RNA (RNA integrity number > 5). Age at death, gender, post mortem
interval and freezer storage time had no effect on RNA quality. Conclusion: Reasonable-quality
RNA can be isolated from samples dissected from archived frozen human
half brains but repeated sampling results in RNA degradation. Better-quality
RNA is obtained from samples placed in RNALater than from snap frozen
samples. The quality and yield of RNA are not affected by age at
death, gender, post mortem interval of >6Â h or freezer storage time.},
doi = {10.1111/j.1365-2990.2011.01162.x},
issn = {1365-2990},
keywords = {brain, Creutzfeldt–Jakob, human, post mortem, RNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2990.2011.01162.x}
}
@ARTICLE{Sheth2011,
author = {Sheth, Sachiv and Li, Xinmin and Binder, Scott and Dry, Sarah M},
title = {Differential gene expression profiles of neurothekeomas and nerve
sheath myxomas by microarray analysis},
journal = {Mod Pathol},
year = {2011},
volume = {24},
pages = {343--354},
number = {3},
month = mar,
issn = {0893-3952},
publisher = {United States and Canadian Academy of Pathology, Inc.},
url = {http://dx.doi.org/10.1038/modpathol.2010.203}
}
@ARTICLE{Shetty2005,
author = {Shetty, Ranjit S. and Bose, Soma C. and Nickell, Melissa D. and McIntyre,
Jeremy C. and Hardin, Debra H. and Harris, Andrew M. and McClintock,
Timothy S.},
title = {Transcriptional changes during neuronal death and replacement in
the olfactory epithelium},
journal = {Molecular and Cellular Neuroscience},
year = {2005},
volume = {30},
pages = {90--107},
number = {1},
month = sep,
abstract = {The olfactory epithelium has the unusual ability to replace its neurons.
We forced replacement of mouse olfactory sensory neurons by bulbectomy.
Microarray, bioinformatics, and in situ hybridization techniques
detected a rapid shift in favor of pro-apoptotic proteins, a progressive
immune response by macrophages and dendritic cells, and identified
or predicted 439 mRNAs enriched in olfactory sensory neurons, including
gene silencing factors and sperm flagellar proteins. Transcripts
encoding cell cycle regulators, axonogenesis proteins, and transcription
factors and signaling proteins that promote proliferation and differentiation
were increased at 5-7 days after bulbectomy and were expressed by
basal progenitor cells or immature neurons. The transcription factors
included Nhlh1, Hes6, Lmyc1, c-Myc, Mxd4, Id1, Nmyc1, Cited2, c-Myb,
Mybl1, Tead2, Dp1, Gata2, Lmo1, and Sox11. The data reveal significant
similarities with embryonic neurogenesis and make several mechanistic
predictions, including the roles of the transcription factors in
the olfactory sensory neuron lineage.},
issn = {1044-7431},
url = {http://www.sciencedirect.com/science/article/B6WNB-4GNCGBB-1/2/ea459c245f36fdf01a46a0a199e079a7}
}
@ARTICLE{Shevchuk2005,
author = {Shevchuk, Taras and Kretzner, Leo and Munson, Kristofer and Axume,
John and Clark, Jarrod and Dyachenko, Olga V. and Caudill, Marie
and Buryanov, Yaroslav and Smith, Steven S.},
title = {Transgene-induced CCWGG methylation does not alter CG methylation
patterning in human kidney cells},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {6124--6136},
number = {19},
month = oct,
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/19/6124}
}
@ARTICLE{Shi2009,
author = {Shi, Changbin and Awad, Issam A. and Jafari, Nadereh and Lin, Simon
and Du, Pan and Hage, Ziad A. and Shenkar, Robert and Getch, Christopher
C. and Bredel, Markus and Batjer, H. Hunt and Bendok, Bernard R.},
title = {Genomics of Human Intracranial Aneurysm Wall},
journal = {Stroke},
year = {2009},
volume = {40},
pages = {1252--1261},
number = {4},
month = apr,
abstract = {Background and Purpose-- The pathogenesis of intracranial aneurysms
(IAs) remains elusive. Most studies have focused on individual genes,
or a few interrelated genes or products, at a time in human IA. However,
a broad view of pathologic mechanisms has not been investigated by
identifying pathogenic genes and their interaction in networks. Our
study aimed to analyze global gene expression patterns in the IA
wall. Methods-- To our knowledge, our group was the first to perform
Illumina microarray analysis on human IA via comparison of aneurysm
wall and superficial temporal artery tissues from 6 consecutive patients.
We adopted stringent statistical criteria to the individual genes;
genes with a false discovery rate <0.01 and >2-fold change were selected
as differentially expressed. To identify the overrepresented biologic
pathways with the differentially expressed genes, we performed hypergeometric
testing of the genes selected by relaxed criteria of P<0.01 and fold
change >1.5. Results-- There are 326 distinct differentially expressed
genes between IA and superficial temporal artery tissues (>2-fold
change) with a false discovery rate <0.01. Analysis of the Kyoto
Encyclopedia of Genes and Genomes pathways revealed the most impacted
functional pathways: focal adhesion, extracellular matrix receptor
interaction, and cell communication. Analysis of the Gene Ontology
also supported the involvement of another 2 potentially important
pathways: inflammatory response and apoptosis. Conclusions-- The
differentially expressed genes in the aneurysm wall may shed light
on aneurysm pathobiology and provide novel targets for therapeutic
intervention. These data will help generate hypotheses for future
studies.},
url = {http://stroke.ahajournals.org/cgi/content/abstract/40/4/1252}
}
@ARTICLE{Shi2011a,
author = {Shi, Cheng-Ying and Yang, Hua and Wei, Chao-Ling and Yu, Oliver and
Zhang, Zheng-Zhu and Jiang, Chang-Jun and Sun, Jun and Li, Ye-Yun
and Chen, Qi and Xia, Tao and Wan, Xiao-Chun},
title = {Deep sequencing of the Camellia sinensis transcriptome revealed candidate
genes for major metabolic pathways of tea-specific compounds},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {131},
number = {1},
abstract = {BACKGROUND:Tea is one of the most popular non-alcoholic beverages
worldwide. However, the tea plant, Camellia sinensis, is difficult
to culture in vitro, to transform, and has a large genome, rendering
little genomic information available. Recent advances in large-scale
RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable
approach to generate large expression datasets for functional genomic
analysis, which is especially suitable for non-model species with
un-sequenced genomes.RESULTS:Using high-throughput Illumina RNA-seq,
the transcriptome from poly (A)+ RNA of C. sinensis was analyzed
at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5
million reads were obtained, trimmed, and assembled into 127,094
unigenes, with an average length of 355 bp and an N50 of 506 bp,
which consisted of 788 contig clusters and 126,306 singletons. This
number of unigenes was 10-fold higher than existing C. sinensis sequences
deposited in GenBank (as of August 2010). Sequence similarity analyses
against six public databases (Uniprot, NR and COGs at NCBI, Pfam,
InterPro and KEGG) found 55,088 unigenes that could be annotated
with gene descriptions, conserved protein domains, or gene ontology
terms. Some of the unigenes were assigned to putative metabolic pathways.
Targeted searches using these annotations identified the majority
of genes associated with several primary metabolic pathways and natural
product pathways that are important to tea quality, such as flavonoid,
theanine and caffeine biosynthesis pathways. Novel candidate genes
of these secondary pathways were discovered. Comparisons with four
previously prepared cDNA libraries revealed that this transcriptome
dataset has both a high degree of consistency with previous EST data
and an approximate 20 times increase in coverage. Thirteen unigenes
related to theanine and flavonoid synthesis were validated. Their
expression patterns in different organs of the tea plant were analyzed
by RT-PCR and quantitative real time PCR (qRT-PCR).CONCLUSIONS:An
extensive transcriptome dataset has been obtained from the deep sequencing
of tea plant. The coverage of the transcriptome is comprehensive
enough to discover all known genes of several major metabolic pathways.
This transcriptome dataset can serve as an important public information
platform for gene expression, genomics, and functional genomic studies
in C. sinensis.},
doi = {10.1186/1471-2164-12-131},
issn = {1471-2164},
pubmedid = {21356090},
url = {http://www.biomedcentral.com/1471-2164/12/131}
}
@ARTICLE{Shi2006,
author = {Shi, Guo-Ping and Dolganov, Gregory M.},
title = {Comprehensive Transcriptome of Proteases and Protease Inhibitors
in Vascular Cells},
journal = {Stroke},
year = {2006},
volume = {37},
pages = {537--541},
number = {2},
month = feb,
abstract = {Background and Purpose-- Smooth muscle cells, endothelial cells, and
macrophages are essential components of the vasculature, of which
the homeostatic gene expression participate importantly in the maintenance
of vascular wall integrity. The pathogenesis of vascular diseases,
such as cerebral ischemia, atherosclerosis, and abdominal aortic
aneurysms, often associates with inflammation and altered gene expression,
including proteolytic enzymes that play multiple and important roles
in extracellular matrix degradation, cell proliferation and migration,
and latent enzyme or growth factor activation. Methods and Results--
Human saphenous vein smooth muscle cells, endothelial cells, and
monocyte-derived macrophages from 3 independent donors were stimulated
with interleukin 1{beta}, interferon {gamma}, tumor necrosis factor
{alpha}, basic fibroblast growth factor, and vascular endothelial
growth factor, 5 common proinflammatory mediators often found in
diseased human microvessels and macrovessels. Quantitative real-time
PCR was used to examine the mRNA levels of 49 proteolytic enzymes
and their inhibitors, selected from 4 protease families, in these
vascular cells. Conclusions-- Although primary cultured cells from
different donors may behave differently in response to these proinflammatory
cytokines, data from this study revealed a broad view of vascular
cell protease expression profiles under inflammatory conditions,
critical to studies of inflammation-associated vascular tissue remodeling.},
url = {http://stroke.ahajournals.org/cgi/content/abstract/37/2/537}
}
@ARTICLE{Shi2006a,
author = {Shi, Hongzhen and Cao, Tinghua and Connolly, John E. and Monnet,
Laurence and Bennett, Lynda and Chapel, Sylvie and Bagnis, Claude
and Mannoni, Patrice and Davoust, Jean and Palucka, A. Karolina and
Banchereau, Jacques},
title = {Hyperthermia Enhances CTL Cross-Priming},
journal = {J. Immunol.},
year = {2006},
volume = {176},
pages = {2134--2141},
number = {4},
month = feb,
abstract = {Dendritic cells (DCs) loaded with killed allogeneic melanoma cells
can cross-prime naive CD8+ T cells to differentiate into melanoma-specific
CTLs in 3-wk cultures. In this study we show that DCs loaded with
killed melanoma cells that were heated to 42{degrees}C before killing
are more efficient in cross-priming of naive CD8+ T cells than DCs
loaded with unheated killed melanoma cells. The enhanced cross-priming
was demonstrated by several parameters: 1) induction of naive CD8+
T cell differentiation in 2-wk cultures, 2) enhanced killing of melanoma
peptide-pulsed T2 cells, 3) enhanced killing of HLA-A*0201+ melanoma
cells in a standard 4-h chromium release assay, and 4) enhanced capacity
to prevent tumor growth in vitro in a tumor regression assay. Two
mechanisms might explain the hyperthermia-induced enhanced cross-priming.
First, heat-treated melanoma cells expressed increased levels of
70-kDa heat shock protein (HSP70), and enhanced cross-priming could
be reproduced by overexpression of HSP70 in melanoma cells transduced
with HSP70 encoding lentiviral vector. Second, hyperthermia resulted
in the increased transcription of several tumor Ag-associated Ags,
including MAGE-B3, -B4, -A8, and -A10. Thus, heat treatment of tumor
cells permits enhanced cross-priming, possibly via up-regulation
of both HSPs and tumor Ag expression.},
url = {http://www.jimmunol.org/cgi/content/abstract/176/4/2134}
}
@ARTICLE{Shi2011,
author = {Shi, Qiang and Cox, Laura A. and Hodara, Vida and Wang, Xing Li and
VandeBerg, John L.},
title = {Repertoire of endothelial progenitor cells mobilized by femoral artery
ligation – A nonhuman primate study},
journal = {Journal of Cellular and Molecular Medicine},
year = {2011},
pages = {no--no},
abstract = {To determine in the baboon model the identities and functional characteristics
of endothelial progenitor cells mobilized in response to artery ligation,
we collected peripheral blood mononuclear cells before and 3 days
after a segment of femoral artery was removed. Our goal was to find
EPC subpopulations with highly regenerative capacity. We identified
12 subpopulations of putative EPCs that were altered >1.75 fold;
two subpopulations (CD146+/CD54-/CD45- at 6.63 fold, and CD146+/UEA-1-/CD45-
at 12.21 fold) were dramatically elevated. To investigate the regenerative
capacity of putative EPCs, we devised a new assay that maximally
resembled their in vivo scenario, we purified CD34+ and CD146+ cells
and co-cultured them with basal and mobilized peripheral blood mononuclear
cells; both cell types took up Dil-LDL, but purified CD146+ cells
exhibited accelerated differentiation by increasing expression of
CD31 and CD144, and by exhibiting more active cord-like structure
formation by comparison to the CD34+ subpopulation in a co-culture
with mobilized PBMNCs. We demonstrate that ischemia due to vascular
ligation mobilizes multiple types of cells with distinct roles. Baboon
CD146+ cells exhibit higher reparative capacity than CD34+ cells,
and thus are a potential source for therapeutic application.},
doi = {10.1111/j.1582-4934.2011.01501.x},
issn = {1582-4934},
keywords = {EPC mobilization♦nonhuman primate model♦ischemia},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2011.01501.x}
}
@ARTICLE{Shi2010,
author = {Shi, Q. and Guo, L. and Patterson, T.A. and Dial, S. and Li, Q. and
Sadovova, N. and Zhang, X. and Hanig, J.P. and Paule, M.G. and Slikker
Jr, W. and Wang, C.},
title = {Gene expression profiling in the developing rat brain exposed to
ketamine},
journal = {Neuroscience},
year = {2010},
volume = {166},
pages = {852--863},
number = {3},
month = mar,
abstract = {Ketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist,
is associated with accelerated neuronal apoptosis in the developing
rodent brain. In this study, postnatal day (PND) 7 rats were treated
with 20 mg/kg ketamine or saline in six successive doses (s.c.) at
2-h intervals. Brain frontal cortical areas were collected 6 h after
the last dose and RNA isolated and hybridized to Illumina Rat Ref-12
Expression BeadChips containing 22,226 probes. Many of the differentially
expressed genes were associated with cell death or differentiation
and receptor activity. Ingenuity Pathway Analysis software identified
perturbations in NMDA-type glutamate, GABA and dopamine receptor
signaling. Quantitative polymerase chain reaction (Q-PCR) confirmed
that NMDA receptor subunits were significantly up-regulated. Up-regulation
of NMDA receptor mRNA signaling was further confirmed by in situ
hybridization. These observations support our working hypothesis
that prolonged ketamine exposure produces up-regulation of NMDA receptors
and subsequent over-stimulation of the glutamatergic system by endogenous
glutamate, triggering enhanced apoptosis in developing neurons.},
issn = {0306-4522},
keywords = {ketamine, gene expression, microarray, TaqMan, N-methyl-d-aspartate
(NMDA) receptor},
url = {http://www.sciencedirect.com/science/article/B6T0F-4Y6455H-1/2/0466a93b522d55a2aa2772ad2f094539}
}
@ARTICLE{Shi2003,
author = {Shi, Run Zhang and Morrissey, Joseph M. and Rowley, Janet D.},
title = {Screening and Quantification of Multiple Chromosome Translocations
in Human Leukemia},
journal = {Clin. Chem.},
year = {2003},
volume = {49},
pages = {1066--1073},
number = {7},
month = jul,
abstract = {Background: Characterization of fusion gene transcripts in leukemia
that result from chromosome translocations provides valuable information
regarding appropriate treatment and prognosis. However, screening
for multiple fusion gene transcripts is difficult with conventional
PCR and state-of-the-art real-time PCR and high-density microarrays.
Methods: We developed a multiplex reverse transcription-PCR (RT-PCR)
assay for screening and quantification of fusion gene transcripts
in human leukemia cells. Chimeric primers were used that contained
gene-specific and universal sequences. PCR amplification of fusion
and control gene transcripts was achieved with use of an excess of
universal primers to allow the ratio of abundance of fusion gene
to endogenous or exogenous controls to be maintained throughout PCR.
Multiplex RT-PCR products analyzed by an ABI 310 Genetic Analyzer
were consistent with those of duplex RT-PCR (single analytical sample
plus control). In addition, multiplex RT-PCR results were analyzed
by an assay using an oligonucleotide microarray that contained probes
for the splice-junction sequences of various fusion transcripts.
Results: The multiplex RT-PCR assay enabled screening of >10 different
fusion gene transcripts in a single reaction. RT-PCR followed by
analysis with the ABI Prism 310 Genetic Analyzer consistently detected
1 fusion-transcript-carrying leukemia cell in 100-10 000 cells. The
assay covered a 1000-fold range. Preliminary results indicate that
multiplex RT-PCR products can also be analyzed by hybridization-based
microarray assay. Conclusions: The multiplex RT-PCR analyzed by either
ABI Prism 310 Genetic Analyzer or microarray provides a sensitive
and specific assay for screening of multiple fusion transcripts in
leukemia, with the latter an assay that is adaptable to a high-throughput
system for clinical screening.},
url = {http://www.clinchem.org/cgi/content/abstract/49/7/1066}
}
@ARTICLE{Shi2006b,
author = {Shi, Wei and Bastianutto, Carlo and Li, Anna and Perez-Ordonez, Bayardo
and Ng, Raymond and Chow, Kan-Yan and Zhang, Wendy and Jurisica,
Igor and Lo, Kwok-Wai and Bayley, Andrew and Kim, John and O'Sullivan,
Brian and Siu, Lillian and Chen, Eric and Liu, Fei-Fei},
title = {Multiple dysregulated pathways in nasopharyngeal carcinoma revealed
by gene expression profiling},
journal = {Int. J. Cancer},
year = {2006},
volume = {119},
pages = {2467--2475},
number = {10},
abstract = {Abstract 10.1002/ijc.22107.abs Gene expression profiling was conducted
using primary human nasopharyngeal carcinoma (NPC) biopsy samples
to improve the understanding of the molecular pathways defining NPC
and to identify novel potential therapeutic targets. RNA samples
were extracted from 36 patients suspected to have NPC and hybridized
onto the Affymetrix U133A chip. NPC was diagnosed in 19 patients,
11 had lymphoid hyperplasia (LH), and 6 were “normal� biopsies.
Clinical stages for these NPC patients ranged from I–IV, including
one M1. All NPC patients (except the M1) were treated with curative
intent, which included radiotherapy alone (4 patients), or combined
with chemotherapy (14 patients). Unsupervised clustering demonstrated
a distinct NPC expression pattern, compared to normal biopsies. Subsequent
Significance Analysis of Microarrays (SAM) derived from 14 NPC and
6 normal samples discovered 1,089 differentially regulated genes.
Pathway analyses revealed novel insights into the mechanisms leading
to NPC, whereby upregulation of NFκB2 and survivin play central
roles in increasing resistance to apoptosis, and changes in integrin
and WNT/β-catenin signaling leading to uncontrolled proliferation.
The role of survivin in resisting apoptosis in NPC was confirmed
by RNA interference. Our data provide novel insights into the development
and progression of NPC, and suggest survivin as a novel therapeutic
target for NPC. © 2006 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {gene expression profiling, nasopharyngeal carcinoma, apoptosis, integrin
signaling, β-catenin},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22107}
}
@ARTICLE{Shi2008,
author = {Shi, Zhen and Blaschek, Hans P.},
title = {Transcriptional Analysis of Clostridium beijerinckii NCIMB 8052 and
the Hyper-Butanol-Producing Mutant BA101 during the Shift from Acidogenesis
to Solventogenesis},
journal = {Appl. Envir. Microbiol.},
year = {2008},
volume = {74},
pages = {7709--7714},
number = {24},
month = dec,
abstract = {Clostridium beijerinckii is an anaerobic bacterium used for the fermentative
production of acetone and butanol. The recent availability of genomic
sequence information for C. beijerinckii NCIMB 8052 has allowed for
an examination of gene expression during the shift from acidogenesis
to solventogenesis over the time course of a batch fermentation using
a ca. 500-gene set DNA microarray. The microarray was constructed
using a collection of genes which are orthologs of members of gene
families previously found to be important to the physiology of C.
acetobutylicum ATCC 824. Similar to the onset of solventogenesis
in C. acetobutylicum 824, the onset of solventogenesis in C. beijerinckii
8052 was concurrent with the initiation of sporulation. However,
forespores and endospores developed more rapidly in C. beijerinckii
8052 than in C. acetobutylicum 824, consistent with the accelerated
expression of the sigE- and sigG-regulated genes in C. beijerinckii
8052. The comparison of gene expression patterns and morphological
changes in C. beijerinckii 8052 and the hyper-butanol-producing C.
beijerinckii strain BA101 indicated that BA101 was less efficient
in sporulation and phosphotransferase system-mediated sugar transport
than 8052 but that it exhibited elevated expression of several primary
metabolic genes and chemotaxis/motility genes.},
url = {http://aem.asm.org/cgi/content/abstract/74/24/7709}
}
@ARTICLE{Shi2008a,
author = {Shi, ZhiHua and Rudzinski, Marcelo and Meerovitch, Karen and Lebrun-Julien,
Frederic and Birman, Elena and Di Polo, Adriana and Saragovi, H.
Uri},
title = {{alpha}2-Macroglobulin Is a Mediator of Retinal Ganglion Cell Death
in Glaucoma},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {29156--29165},
number = {43},
month = oct,
abstract = {Glaucoma is defined as a chronic and progressive optic nerve neuropathy,
characterized by apoptosis of retinal ganglion cells (RGC) that leads
to irreversible blindness. Ocular hypertension is a major risk factor,
but in glaucoma RGC death can persist after ocular hypertension is
normalized. To understand the mechanism underlying chronic RGC death
we identified and characterized a gene product, {alpha}2-macroglobulin
({alpha}2M), whose expression is up-regulated early in ocular hypertension
and remains up-regulated long after ocular hypertension is normalized.
In ocular hypertension retinal glia up-regulate {alpha}2M, which
binds to low-density lipoprotein receptor-related protein-1 receptors
in RGCs, and is neurotoxic in a paracrine fashion. Neutralization
of {alpha}2M delayed RGC loss during ocular hypertension; whereas
delivery of {alpha}2M to normal eyes caused progressive apoptosis
of RGC mimicking glaucoma without ocular hypertension. This work
adds to our understanding of the pathology and molecular mechanisms
of glaucoma, and illustrates emerging paradigms for studying chronic
neurodegeneration in glaucoma and perhaps other disorders.},
url = {http://www.jbc.org/cgi/content/abstract/283/43/29156}
}
@ARTICLE{Shi-Wen2009,
author = {Shi-Wen, Xu and Parapuram, Sunil K. and Pala, Daphne and Chen, Yunliang
and Carter, David E. and Eastwood, Mark and Denton, Christopher P.
and Abraham, David J. and Leask, Andrew},
title = {Requirement of transforming growth factor β–activated kinase 1
for transforming growth factor β–induced α-smooth muscle actin
expression and extracellular matrix contraction in fibroblasts},
journal = {Arthritis \& Rheumatism},
year = {2009},
volume = {60},
pages = {234--241},
number = {1},
abstract = {Abstract 10.1002/art.24223.abs Objective Fibrosis is believed to occur
through normal tissue remodeling failing to terminate. Tissue repair
intimately involves the ability of fibroblasts to contract extracellular
matrix (ECM), and enhanced ECM contraction is a hallmark of fibrotic
cells in various conditions, including scleroderma. Some fibrogenic
transcriptional responses to transforming growth factor β (TGFβ),
including α-smooth muscle actin (α-SMA) expression and ECM contraction,
require focal adhesion kinase/Src (FAK/Src). The present study was
undertaken to assess whether TGFβ-activated kinase 1 (TAK1) acts
downstream of FAK/Src to mediate fibrogenic responses in fibroblasts.
Methods We used microarray, real-time polymerase chain reaction,
Western blot, and collagen gel contraction assays to assess the ability
of wild-type and TAK1-knockout fibroblasts to respond to TGFβ1.
Results The ability of TGF to induce TAK1 was blocked by the FAK/Src
inhibitor PP2. JNK phosphorylation in response to TGFβ1 was impaired
in the absence of TAK1. TGFβ could not induce matrix contraction
or expression of a group of fibrotic genes, including α-SMA, in
the absence of TAK1. Conclusion These results suggest that TAK1 operates
downstream of FAK/Src in mediating fibrogenic responses and that
targeting of TAK1 may be a viable antifibrotic strategy in the treatment
of certain disorders, including scleroderma.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.24223}
}
@ARTICLE{Shi-wen2006,
author = {Shi-wen, Xu and Stanton, Lee Anne and Kennedy, Laura and Pala, Daphne
and Chen, Yunliang and Howat, Sarah L. and Renzoni, Elisabetta A.
and Carter, David E. and Bou-Gharios, George and Stratton, Richard
J. and Pearson, Jeremy D. and Beier, Frank and Lyons, Karen M. and
Black, Carol M. and Abraham, David J. and Leask, Andrew},
title = {CCN2 Is Necessary for Adhesive Responses to Transforming Growth Factor-beta1
in Embryonic Fibroblasts},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {10715--10726},
number = {16},
month = apr,
abstract = {CCN2 is induced by transforming growth factor-[beta] (TGF[beta]) in
fibroblasts and is overexpressed in connective tissue disease. CCN2
has been proposed to be a downstream mediator of TGF[beta] action
in fibroblasts; however, the role of CCN2 in regulating this process
unclear. By using embryonic fibroblasts isolated from ccn2-/-mice,
we showed that CCN2 is required for a subset of responses to TGF[beta].
Affymetrix genome-wide expression profiling revealed that 942 transcripts
were induced by TGF[beta] greater than 2-fold in ccn2+/+ fibroblasts,
of which 345 were not induced in ccn2-/-fibroblasts, including pro-adhesive
and matrix remodeling genes. Whereas TGF[beta] properly induced a
generic Smad3-responsive promoter in ccn2-/-fibroblasts, TGF[beta]-induced
activation of focal adhesion kinase (FAK) and Akt was reduced in
ccn2-/-fibroblasts. Emphasizing the importance of FAK and Akt activation
in CCN2-dependent transcriptional responses to TGF[beta] in fibroblasts,
CCN2-dependent transcripts were not induced by TGF[beta] in fak-/-fibroblasts
and were reduced by wortmannin in wild-type fibroblasts. Akt1 overexpression
in ccn2-/-fibroblasts rescued the TGF[beta]-induced transcription
of CCN2-dependent mRNA. Finally, induction of TGF[beta]-induced fibroblast
adhesion to fibronectin and type I collagen was significantly diminished
in ccn2-/-fibroblasts. Thus in embryonic fibroblasts, CCN2 is a necessary
cofactor required for TGF[beta] to activate the adhesive FAK/Akt/phosphatidylinositol
3-kinase cascade, FAK/Akt-dependent genes, and adhesion to matrix.},
url = {http://www.jbc.org/cgi/content/abstract/281/16/10715}
}
@ARTICLE{Shiao2008,
author = {Shiao, Yu-Ming and Chang, Ya-Hui and Liu, Yen-Ming and Li, Jian-Chiuan
and Su, Jih-Shyun and Liu, Ko-Jiunn and Liu, Yu-Fen and Lin, Ming-Wei
and Tsai, Shih-Feng},
title = {Dysregulation of GIMAP genes in non-small cell lung cancer},
journal = {Lung Cancer},
year = {2008},
volume = {62},
pages = {287--294},
number = {3},
month = dec,
abstract = {Summary The GIMAP (GTPase of the immunity-associated protein) gene
family includes seven functional members residing on human chromosome
7. GIMAP genes encode GTP-binding proteins that share a unique primary
structure and whose function is largely unknown. However, gene ablation
studies reveal that Gimap4 plays an important role in regulating
the apoptosis of T cells. In a pilot microarray analysis on six cases
of non-small cell lung cancer (NSCLC), we discovered that the expression
of GIMAP family members, but not the neighboring non-GIMAP genes,
was uniformly lower in the tumor tissues, compared to that in the
adjacent nontumor tissues. This finding was subsequently confirmed
by quantitative PCR assays in a total of twenty NSCLCs, and we found
that GIMAP6 and GIMAP8 showed striking reduction of gene expression
in the tumors. In contrast, GIMAP8 mRNA level was abnormally elevated
in the adjacent nontumor tissues as compared to that in the control
lung tissues. Such reciprocal expression of GIMAPs suggests that
this unique gene family might contribute to the pathogenesis of and
immune reactions to NSCLC.},
issn = {0169-5002},
keywords = {Adenocarcinoma, Gene expression, Immunity, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6T9C-4SFHH9N-1/2/9d5b3e43c738310efef9b15952246900}
}
@ARTICLE{Shiba-Ishii2011,
author = {Shiba-Ishii, Aya and Kano, Junko and Morishita, Yukio and Sato, Yukio
and Minami, Yuko and Noguchi, Masayuki},
title = {High expression of stratifin is a universal abnormality during the
course of malignant progression of early-stage lung adenocarcinoma},
journal = {International Journal of Cancer},
year = {2011},
volume = {129},
pages = {2445--2453},
number = {10},
abstract = {Adenocarcinoma in situ (AIS) of the lung has an extremely favorable
prognosis, with a 5-year survival rate of 100%. However, early invasive
adenocarcinoma (EIA) often has a fatal outcome. In this study, we
compared the expression profiles of AIS with those of EIA showing
lymph node metastasis or a fatal outcome, and screened the differentially
expressed genes by cDNA microarray. From the genes selected, we focused
on Stratifin (SFN, 14-3-3 σ), which showed significantly higher
expression in EIA than in AIS. Immunohistochemistry for SFN revealed
that more than 95% of EIAs were immunopositive for SFN, in comparison
to only 13% of AISs (p <0.05). Interestingly, positivity was detected
not only in the invasive region but also in the in situ spreading
component of EIA. Functionally, SFN facilitates the cell proliferation
capacity of lung adenocarcinoma. These results indicate that SFN
overexpression is a universal abnormality during the stepwise progression
from in situ to invasive adenocarcinoma of the lung.},
doi = {10.1002/ijc.25907},
issn = {1097-0215},
keywords = {lung cancer, tumor promotion and progression, stratifin, adenocarcinoma},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25907}
}
@ARTICLE{Shibata2011,
author = {Shibata, Michio and Ishimatsu-Tsuji, Yumiko and Yokoo, Mihoshi and
Nakai, Yuji and Abe, Keiko and Muta, Keiko},
title = {Effect of oral intake of winged bean extract on a skin lichenification
model: Evaluation by microarray analysis},
journal = {BioFactors},
year = {2011},
volume = {37},
pages = {421--428},
number = {6},
abstract = {Winged bean (WB), Psophocarpus tetragonolobus, is a tropical legume,
the potential of which is not fully understood. We found that 5-week
oral administration of a WB seed extract inhibited wrinkle formation
induced by repeated tape stripping (TS) as a model of lichenification
in human chronic eczematous dermatitis. To elucidate the mechanism
of the effect of WB on this model, we applied microarray analysis.
Hierarchical clustering revealed that each experimental group formed
a distinct cluster, suggesting the presence of a distinct gene expression
profile among the three groups of non-TS, TS, and TS with oral administration
of WB extract (TS/WB). Gene ontology analysis showed that several
gene groups with keratinization and mitosis were significantly upregulated
by TS, while other groups with ATP synthesis and glycolysis were
significantly downregulated by TS/WB. Moreover, WB extract influenced
a number of genes related to epidermal differentiation and inflammation.
This suggests that these changes inhibited wrinkle formation by TS.},
doi = {10.1002/biof.182},
issn = {1872-8081},
keywords = {winged bean, microarray, wrinkle formation, epidermal differentiation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/biof.182}
}
@ARTICLE{Shibata2009,
author = {Shibata, Yasuko and Araki, Hidefumi and Oshitani, Toshiyuki and Imaoka,
Asayo and Matsui, Masaru and Miyazawa, Keiji and Abiko, Yoshimitsu},
title = {Effects of linear polarized infrared light irradiation on the transcriptional
regulation of IL-8 expression in IL-1[beta]-stimulated human rheumatoid
synoviocytes involves phosphorylation of the NF-[kappa]B RelA subunit},
journal = {Journal of Photochemistry and Photobiology B: Biology},
year = {2009},
volume = {94},
pages = {164--170},
number = {3},
month = mar,
abstract = {Although recent clinical studies have shown that laser therapy acts
as an anti-inflammatory effector in the treatment of some diseases,
little is known about the mechanism by which it acts in rheumatoid
arthritis (RA) patients. The purpose of our work was to examine how
irradiation with linear polarized infrared light (LPIL) suppresses
inflammatory responses in the MH7A rheumatoid fibroblast-like synoviocyte
cell line. We initially confirmed the effects of two disease-modifying
anti-rheumatic treatments, LPIL irradiation and dexamethasone (Dex)
administration, under experimental inflammatory conditions using
gene chip technology. We found that LPIL exerted a smaller effect
on gene transcription than Dex; however, IL-1[beta]-inducible target
genes such as the CXCL type chemokines IL-8, IL-1[beta] and IL-6
were all clearly suppressed by LPIL to the same degree as by Dex.
We also found that IL-1[beta]-induced release of IL-8 from MH7A cells
was completely blocked by pretreatment with the (IL-8) inhibitor
Bay11-7085, indicating that activation of NF-[kappa]B signaling plays
an important role in the secretion of IL-8. Although the levels of
NFKB1 and RELA transcription were unaffected by IL-1[beta] stimulation,
phosphorylation of RelA S276 was suppressed by both LPIL and Dex.
Thus LPIL likely exerts its anti-inflammatory effects by inhibiting
the release of the inflammatory chemokine IL-8. A fuller understanding
of the anti-inflammatory mechanism of LPIL in rheumatoid synoviocytes
could serve as the basis for improved treatment of RA patients in
the future.},
issn = {1011-1344},
keywords = {Photodynamic therapy, Rheumatoid arthritis, Interleukin-8, NF-[kappa]B
RelA phosphorylation, GeneChip microarray},
url = {http://www.sciencedirect.com/science/article/B6TH0-4V3HHG3-1/2/b5d3e7355096bc4b65ffd883a40ce4d8}
}
@ARTICLE{Shibru2008,
author = {Shibru, Daniel and Hwang, Jimmy and Khanafshar, Elham and Duh, Quan-Yang
and Clark, Orlo H. and Kebebew, Electron},
title = {Does the 3-gene diagnostic assay accurately distinguish benign from
malignant thyroid neoplasms?},
journal = {Cancer},
year = {2008},
volume = {113},
pages = {930--935},
number = {5},
abstract = {Abstract 10.1002/cncr.23703.abs BACKGROUND. A 3-gene (PCSK2, PLAB,
CCND2) assay has been reported to have high accuracy for distinguishing
benign from malignant thyroid tumors that are often indeterminate
on fine–needle aspiration (FNA) biopsy. The aim of the current
study was to determine the diagnostic accuracy of the 3-gene assay
in thyroid tissue and in FNA biopsy for distinguishing benign from
malignant thyroid neoplasms. METHODS. The messenger ribonucleic acid
(mRNA) expression level of 3 genes (PCSK2, PLAB, CCND2) was analyzed
by real-time quantitative reverse transcriptase–polymerase chain
reaction in 261 frozen thyroid tissue samples (138 benign and 123
malignant), and prospectively, in 144 clinical thyroid FNA samples.
To determine the diagnostic accuracy of the 3-gene assay, the area
under the curve (AUC) of the receiver operating characteristic curve
for each gene individually and in combination was determined. RESULTS.
PCSK2 and CCND2 mRNA expression levels were found to be significantly
different between benign and malignant thyroid tissue samples (P
< .0001 and P = .0007, respectively), but PLAB mRNA expression level
was not (P = .099). In the thyroid tissue samples, the AUC was 0.67
for PCSK2 and 0.62 for CCND2. In the thyroid FNA samples, PCSK2 and
CCND2 were significantly differentially expressed between benign
and malignant samples (P = .039 and P = .023, respectively). The
AUC was 0.59 for PCSK2 and 0.61 for CCND2. CONCLUSIONS. Although
PCSK2 and CCND2 were significantly differentially expressed between
benign and malignant thyroid tumors both in tissue and in FNA samples,
the diagnostic accuracy of the 3-gene assay was low. These findings
demonstrate that it is essential for studies to validate the diagnostic
accuracy and clinical utility of emerging candidate diagnostic thyroid
cancer markers if they are to be translated into clinically useful
markers for making patient care decisions. Cancer 2008. © 2008 American
Cancer Society.},
issn = {1097-0142},
keywords = {3-gene assay, diagnosis, thyroid cancer, polymerase chain reaction,
fine–needle aspiration biopsy},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.23703}
}
@ARTICLE{Shih2009,
author = {Shih, Barbara and Wijeratne, Dulharie and Armstrong, Daniel J. and
Lindau, Tommy and Day, Philip and Bayat, Ardeshir},
title = {Identification of Biomarkers in Dupuytren's Disease by Comparative
Analysis of Fibroblasts Versus Tissue Biopsies in Disease-Specific
Phenotypes},
journal = {The Journal of Hand Surgery},
year = {2009},
volume = {34},
pages = {124--136},
number = {1},
month = jan,
abstract = {Purpose Biomarkers are molecular mediators that can serve as indicators
of normal biological processes, pathologic processes, and therapeutic
interventions. This study aims to identify potential biomarkers in
Dupuytren's disease (DD), a fibroproliferative benign tumor with
an unknown etiology and high recurrence after surgery.Methods Bioinformatic
analytical techniques were employed to identify candidate genes that
may be differentially expressed in DD, which included gene expression
analysis of microarray data and thorough literature searches in genetic
linkage and other related biomolecular studies. All DD cases were
males with advanced DD (n = 5, 66 years ± 14). RNA was extracted
from biopsies and corresponding cultures of normal fascia (unaffected
transverse palmar fascia), palmar nodule and cord from each patient.
Real-time reverse transcription-polymerase chain reactions were performed
to determine the gene expression levels for disease-related transcripts.Results
The bioinformatic analysis revealed 25 candidate genes, which were
further short-listed to 6 genes via functional annotation. The 6
selected candidate genes included: A disintegrin and metalloproteinase
domain (ADAM12), aldehyde dehydrogenase 1 family member (ALDH1) A1,
Iroquois homeobox protein 6 (IRX6), proteoglycan 4 (PRG4), tenascin
C (TNC), and periostin (POSTN). The culturing treatments were shown
to have significant impact on the gene expression for ALDH1A1, PRG4,
and TNC. In tissue biopsies, significant fold changes were observed
for ADAM12, POSTN, and TNC in the cord and/or nodule when compared
with that of normal fascia. ADAM12 and POSTN are associated with
accelerated or abnormal cell growth, whereas TNC has been associated
with fibrotic diseases and cell migration.Conclusions This study
demonstrated differential gene expression results in DD tissue biopsies
compared with that of their corresponding cultures. ADAM12, POSTN,
and TNC were identified from the cord and nodule biopsy samples as
potential biomarkers in relation to DD development.},
issn = {0363-5023},
keywords = {Biomarkers, Dupuytren's contracture, Dupuytren's disease, Dupuytren's
tissue and fibroblasts culture, RT-qPCR},
url = {http://www.sciencedirect.com/science/article/B6WJK-4V8VN9S-N/2/aee1af22859327a1214777aab54e86ed}
}
@ARTICLE{Shih2004,
author = {Shih, Joanna H. and Michalowska, Aleksandra M. and Dobbin, Kevin
and Ye, Yumei and Qiu, Ting Hu and Green, Jeffrey E.},
title = {Effects of pooling mRNA in microarray class comparisons},
journal = {Bioinformatics},
year = {2004},
volume = {20},
pages = {3318--3325},
number = {18},
month = dec,
abstract = {Motivation: In microarray experiments investigators sometimes wish
to pool RNA samples before labeling and hybridization due to insufficient
RNA from each individual sample or to reduce the number of arrays
for the purpose of saving cost. The basic assumption of pooling is
that the expression of an mRNA molecule in the pool is close to the
average expression from individual samples. Recently, a method for
studying the effect of pooling mRNA on statistical power in detecting
differentially expressed genes between classes has been proposed,
but the different sources of variation arising in microarray experiments
were not distinguished. Another paper recently did take different
sources of variation into account, but did not address power and
sample size for class comparison. In this paper, we study the implication
of pooling in detecting differential gene expression taking into
account different sources of variation and check the basic assumption
of pooling using data from both the cDNA and Affymetrix GeneChip
microarray experiments. Results: We present formulas for the required
number of subjects and arrays to achieve a desired power at a specified
significance level. We show that due to the loss of degrees of freedom
for a pooled design, a large increase in the number of subjects may
be required to achieve a power comparable to that of a non-pooled
design. The added expense of additional samples for the pooled design
may outweigh the benefit of saving on microarray cost. The microarray
data from both platforms show that the major assumption of pooling
may not hold. Supplementary information: Supplementary material referenced
in the text is available at http://linus.nci.nih.gov/brb/TechReport.htm},
url = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/20/18/3318}
}
@ARTICLE{Shih2011,
author = {Shih, Karin K. and Qin, Li-Xuan and Tanner, Edward J. and Zhou, Qin
and Bisogna, Maria and Dao, Fanny and Olvera, Narciso and Viale,
Agnes and Barakat, Richard R. and Levine, Douglas A.},
title = {A microRNA survival signature (MiSS) for advanced ovarian cancer},
journal = {Gynecologic Oncology},
year = {2011},
volume = {121},
pages = {444--450},
number = {3},
month = jun,
abstract = {Objectives MicroRNAs (miRNAs) are a class of small non-coding RNAs
that negatively regulate gene expression primarily through post-transcriptional
modification. We tested the hypothesis that miRNA expression is associated
with overall survival in advanced ovarian cancer.Methods Cases included
newly diagnosed patients with stage III or IV serous ovarian cancer.
RNA from a training set of 62 cases was hybridized to an miRNA microarray
containing 470 mature human transcripts. Cox Regression was performed
to identify miRNAs associated with overall survival. External validation
was performed using quantitative RT-PCR miRNA assays in an independent
test set of 123 samples. MiRNA targets and associated biologic pathways
were predicted in silico.Results Of all patients, 80% had high-grade,
stage IIIC tumors and 64% underwent optimal cytoreduction. The median
survival for the entire cohort was 49 ± 4 months. The training set
identified 3 miRNAs associated with survival -- miR-337, miR-410,
and miR-645. An miRNA signature containing miR-410 and miR-645 was
most strongly associated with overall survival in the training set
(HR = 2.96, 95% CI: 1.51-5.78). This miRNA survival signature (MiSS)
was validated in the test set (HR = 1.71, 95% CI: 1.05-2.78). The
MiSS was independent of FIGO stage and surgical debulking.Conclusions
The data suggest that an MiSS that contains miR-410 and miR-645 is
negatively associated with overall survival in advanced serous ovarian
cancer. This signature, when further validated, may be useful in
individualizing care for the ovarian cancer patient. Pathway analyses
identify biologically plausible mechanisms.},
issn = {0090-8258},
keywords = {MicroRNA, Gene expression, Overall survival, Advanced ovarian cancer},
url = {http://www.sciencedirect.com/science/article/pii/S0090825811000692}
}
@ARTICLE{Shiirevnyamba2011,
author = {Shiirevnyamba, A and Takahashi, T and Shan, H and Ogawa, H and Yano,
S and Kanayama, H and Izumi, K and Uehara, H},
title = {Enhancement of osteoclastogenic activity in osteolytic prostate cancer
cells by physical contact with osteoblasts},
journal = {Br J Cancer},
year = {2011},
volume = {104},
pages = {505--513},
number = {3},
month = feb,
issn = {0007-0920},
publisher = {Cancer Research UK},
url = {http://dx.doi.org/10.1038/sj.bjc.6606070}
}
@ARTICLE{Shim2011,
author = {Joong Hyun Shim and Dong Wook Shin and Tae Ryong Lee and Hak Hee
Kang and Sun Hee Jin and Minsoo Noh},
title = {The retinoic acid-induced up-regulation of insulin-like growth factor
1 and 2 is associated with prolidase-dependent collagen synthesis
in UVA-irradiated human dermal equivalents},
journal = {Journal of Dermatological Science},
year = {2011},
pages = { - },
number = {0},
abstract = {Background Ultraviolet (UV) A irradiation causes the degeneration
of extracellular matrix in the skin dermis, mainly due to disrupted
collagen homeostasis, resulting in the photo-aging of human skin.
All-trans retinoic acid (ATRA) improves photo-aged human skin in
vivo. Objectives Although the effects of ATRA on collagen synthesis
and MMP regulation are well known, the effects of ATRA on other collagen
homeostasis-associated genes have not been elucidated. This study
was aimed to study the factors that are pharmacologically associated
with the effect of ATRA on collagen homeostasis. Methods The gene
transcription profile of collagen homeostasis-associated genes was
systematically evaluated in three-dimensional human dermal equivalents
(HDEs) following UVA-irradiation and/or ATRA treatment. Results In
addition to the expected changes in MMPs and collagen synthesis in
HDEs in response to ATRA, prolidase, an important enzyme in the recycling
of proline and hydroxyproline from degraded collagen molecules, was
significantly decreased by UVA irradiation, and its down-regulation
was antagonized by ATRA. Transfection with a prolidase-specific siRNA
led to a significant decrease in procollagen synthesis in human fibroblasts.
ATRA inhibited the UVA irradiation-induced decrease in prolidase
activity through an insulin-like growth factor (IGF) receptor signaling
pathway in HDEs. ARTA increased IGF1 and IGF2 production in HDEs,
and neutralizing IGFs with anti-IGF antibodies abolished the effect
of ATRA on proliase activity. Conclusions These data demonstrate
that ATRA regulates prolidase activity in HDEs via IGF receptor signaling,
suggesting one of the pharmacological mechanisms by which improves
photo-aged human skin.},
doi = {10.1016/j.jdermsci.2011.12.008},
issn = {0923-1811},
keywords = {Prolidase},
url = {http://www.sciencedirect.com/science/article/pii/S0923181111003586}
}
@ARTICLE{Shim2004,
author = {Shim, Mi-Hyun and Hoover, Aubree and Blake, Noel and Drachman, Jonathan
G. and Reems, Jo Anna},
title = {Gene expression profile of primary human CD34+CD38lo cells differentiating
along the megakaryocyte lineage},
journal = {Experimental Hematology},
year = {2004},
volume = {32},
pages = {638--648},
number = {7},
month = jul,
abstract = {Objective To identify genes involved in megakaryopoiesis, high-density
oligonucleotide microarrays were used to compare transcript profiles
from undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes
(MKs).Materials and methods Megakaryocyte differentiation was achieved
in vitro by inducing primary human CD34+CD38lo cells in serum-deprived
media supplemented with the cytokine combination of interleukin-3,
interleukin-6, stem cell factor, and thrombopoietin for 10 days.
Three replicate microarray experiments were performed using hematopoietic
cells isolated from three different organ donors and high-density
oligonucleotide microarrays.Results Analysis of gene array data resulted
in 304 differentially expressed genes (p <= 0.001, fold change >=3).
A third of the 25 most highly up-regulated genes were known to participate
in hemostasis (z = 6.75), and no genes known to be associated with
MKs were among the down-regulated genes. We also found a large proportion
of up-regulated transcripts in gene ontology categories of adhesion
and receptor activity (85%) and signal transduction activity (68%).
At the same time, 70% of genes within transcription factor functions
were down-regulated. Confirmatory studies indicated that the array
results correlated with mRNA and protein expression levels in primary
MKs.Conclusion This study provides a global expression profile of
human MKs and a list of novel and previously uncharacterized candidate
genes that are important components of megakaryopoiesis.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4CTB87T-8/2/340fb3de695133a0dc1725e45f0693bd}
}
@ARTICLE{Shima2008,
author = {Shima, Tatsuichiro and Fukushima, Kouhei and Setoyama, Hiromi and
Imaoka, Akemi and Matsumoto, Satoshi and Hara, Taeko and Suda, Kazunori
and Umesaki, Yoshinori},
title = {Differential effects of two probiotic strains with different bacteriological
properties on intestinal gene expression, with special reference
to indigenous bacteria},
journal = {FEMS Immunology \& Medical Microbiology},
year = {2008},
volume = {52},
pages = {69--77},
number = {1},
abstract = {Abstract Probiotics are used for the improvement of gut disorders.
To explore the potential of probiotics, a gnotobiotic study using
BALB/c mice to analyze epithelial gene expression was performed.
Microarray analysis of probiotic strain-monoassociated mice showed
that Lactobacillus casei Shirota and Bifidobacterium breve Yakult
noticeably affected gene expression in the ileal and colonic epithelial
cells, respectively, although to a smaller extent than segmented
filamentous bacteria (SFB). Lactobacillus casei Shirota enhanced
the gene expression involving defense/immune functions and lipid
metabolism more strongly than B. breve Yakult. In the colon, expression
of a chloride transporter was slightly enhanced, although downregulation
of many genes, such as guanine nucleotide-binding protein, was evident
in mice with B. breve Yakult compared with the ones with L. casei
Shirota. SFB affected gene expression more strongly than the probiotic
strains. In particular, α(1–2) fucosyltransferase and pancreatitis-associated
protein were significantly enhanced only in SFB-monoassociated mice
but not probiotic strain-monoassociated mice. Gene expression of
SFB-monoassociated mice was either stimulated or repressed in a manner
similar to or opposite that of conventional colonized mice. Taken
together, probiotic strains of L. casei Shirota and B. breve Yakult
differentially affect epithelial gene expression in the small intestine
and colon, respectively.},
issn = {1574-695X},
keywords = {gene expression, indigenous bacteria, probiotic, mouse intestine},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-695X.2007.00344.x}
}
@ARTICLE{Shimada2011,
author = {Shimada, Shu and Mimata, Ayako and Sekine, Masaki and Mogushi, Kaoru
and Akiyama, Yoshimitsu and Fukamachi, Hiroshi and Jonkers, Jos and
Tanaka, Hiroshi and Eishi, Yoshinobu and Yuasa, Yasuhito},
title = {Synergistic tumour suppressor activity of E-cadherin and p53 in a
conditional mouse model for metastatic diffuse-type gastric cancer},
journal = {Gut},
year = {2011},
pages = {gutjnl-2011-300050},
abstract = {BackgroundGastric cancer is the second most frequent cause of death
from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting
a poor prognosis. Germline mutations of CDH1, encoding E-cadherin,
have been reported in hereditary DGC, and genetic and/or epigenetic
alterations of CDH1 are frequently detected in sporadic DGC. Genetic
alterations of TP53 are also frequently found in DGC. To examine
the synergistic effect of the loss of E-cadherin and p53 on gastric
carcinogenesis, a mouse line was established in which E-cadherin
and p53 are specifically inactivated in the stomach parietal cell
lineage. MethodsAtp4b-Cre mice were crossed with Cdh1loxP/loxP and
Trp53loxP/loxP mice, and the gastric phenotype of Atp4b-Cre+;Cdh1loxP/loxP;Trp53loxP/loxP
double conditional knockout (DCKO) mice was examined. ResultsNon-polarised
E-cadherin-negative parietal cells and proton pump-negative atypical
foci were observed in DCKO mice. Intramucosal cancers and invasive
cancers composed of poorly differentiated carcinoma cells and signet
ring cells, histologically very similar to those in humans, were
found from 6 to 9 months, respectively. Fatal DGC developed at 100%
penetrance within a year, frequently metastasised to lymph nodes,
and had tumourigenic activity in immunodeficient mice. Gene expression
profiles of DGC in DCKO mice also resembled those of human DGC, and
mesenchymal markers and epithelial-mesenchymal transition-related
genes were highly expressed in mouse DGC as in human DGC. ConclusionThis
mouse line is the first genetically engineered mouse model of DGC
and is very useful for clarifying the mechanism underlying gastric
carcinogenesis, and provides a new approach to the treatment and
prevention of DGC.},
doi = {10.1136/gutjnl-2011-300050},
url = {http://gut.bmj.com/cgi/content/abstract/gutjnl-2011-300050v1}
}
@ARTICLE{Shimada2011a,
author = {Shimada, Tadanaga and Oda, Shigeto and Sadahiro, Tomohito and Nakamura,
Masataka and Hirayama, Yoh and Watanabe, Eizo and Abe, Ryuzo and
Nakada, Taka-aki and Tateishi, Yoshihisa and Otani, Shunsuke and
Hirasawa, Hiroyuki and Tokuhisa, Takeshi and Uno, Hajime},
title = {Outcome prediction in sepsis combined use of genetic polymorphisms
- A study in Japanese population},
journal = {Cytokine},
year = {2011},
volume = {54},
pages = {79--84},
number = {1},
month = apr,
abstract = {Genetic polymorphisms have recently been found to be related to clinical
outcome in septic patients. The present study investigated to evaluate
the influence of genetic polymorphisms in Japanese septic patients
on clinical outcome and whether use of genetic polymorphisms as predictors
would enable more accurate prediction of outcome. Effects of 16 genetic
polymorphisms related to pro-inflammatory mediators and conventional
demographic/clinical parameters (age, sex, past medical history,
and APACHE II score) on ICU mortality as well as disease severity
during ICU stay were examined in the septic patients (n = 123) admitted
to the ICU between October 2001 and November 2007 by multivariable
logistic regression analysis. ICU mortality was significantly associated
with TNF -308GA, IL1[beta] -31CT/TT, and APACHE II score. Receiver-operating
characteristics (ROC) analysis demonstrated that, compared with APACHE
II score alone (ROC-AUC = 0.68), use of APACHE II score and two genetic
parameters (TNF -308 and IL1[beta] -31) enabled more accurate prediction
of ICU mortality (ROC-AUC = 0.80). Significant association of two
genetic polymorphisms, TNF -308 and IL1[beta] -31, with ICU mortality
was observed in septic patients. In addition, combined use of these
genetic parameters with APACHE II score may enable more accurate
prediction of outcome in septic patients.},
issn = {1043-4666},
keywords = {Genetics, Interleukin-1, Tumor necrosis factor, Sepsis, Risk factors},
url = {http://www.sciencedirect.com/science/article/pii/S1043466610007726}
}
@ARTICLE{Shimizu2010,
author = {Shimizu, Satoshi and Takehara, Tetsuo and Hikita, Hayato and Kodama,
Takahiro and Miyagi, Takuya and Hosui, Atsushi and Tatsumi, Tomohide
and Ishida, Hisashi and Noda, Takehiro and Nagano, Hiroaki and Doki,
Yuichiro and Mori, Masaki and Hayashi, Norio},
title = {The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates
sorafenib-induced apoptosis in human hepatocellular carcinoma},
journal = {J Hepatol},
year = {2010},
volume = {52},
pages = {698--704},
number = {5},
month = may,
abstract = {Bcl-xL, an anti-apoptotic member of the Bcl-2 family, is over-expressed
in human hepatocellular carcinoma, conferring a survival advantage
to tumour cells. The mechanisms underlying its dysregulation have
not been clarified. In the present study, we explored the involvement
of microRNAs that act as endogenous sequence-specific suppressors
of gene expression. The expression profiles of microRNAs in Huh7
hepatoma cells and primary human hepatocytes were compared by microarray
analysis. The effect of let-7 on Bcl-xL expression was examined by
Western blot and a reporter assay. The involvement of let-7 microRNAs
in human tissues was analysed by western blot and reverse transcription-PCR.
Microarray analysis, followed by in silico target prediction, identified
let-7 microRNAs as being downregulated in Huh7 hepatoma cells in
comparison with primary human hepatocytes, as well as possessing
a putative target site in the bcl-xl mRNA. Over-expression of let-7c
or let-7g led to a clear decrease of Bcl-xL expression in Huh7 and
HepG2 cell lines. Reporter assays revealed direct post-transcriptional
regulation involving let-7c or let-7g and the 3′-untranslated region
of bcl-xl mRNA. Human hepatocellular carcinoma tissues with low expression
of let-7c displayed higher expression of Bcl-xL protein than those
with high expression of let-7c, suggesting that low let-7 microRNA
expression contributes to Bcl-xL over-expression. Finally, expression
of let-7c enhanced apoptosis of hepatoma cells upon exposure to sorafenib,
which downregulates expression of another anti-apoptotic Bcl-2 protein,
Mcl-1. let-7 microRNAs negatively regulate Bcl-xL expression in human
hepatocellular carcinomas and induce apoptosis in cooperation with
an anti-cancer drug targeting Mcl-1.},
issn = {0168-8278},
keywords = {Liver, Mcl-1, Bcl-2, Tumour, Epigenetic, miRNA, microRNA, 3′UTR,
3′-untranslated region, mRNA, messenger RNA, HCC, hepatocellular
carcinoma, CDK, cyclin-dependent kinase, DMEM, Dulbecco’s modified
Eagle medium, RT, reverse transcription, PCR, polymerase chain reaction,
7-AAD, 7-amino-actinomycin D, DMSO, dimethyl sulfoxide},
publisher = {Elsevier,},
refid = {S0168-8278(10)00082-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0168827810000826?showall=true}
}
@ARTICLE{Shimizu2011,
author = {Shimizu, Taro and Kubota, Takehiko and Nakasone, Naohiro and Abe,
Daisuke and Morozumi, Toshiya and Yoshie, Hiromasa},
title = {Microarray and quantitative RT-PCR analyses in calcium-channel blockers
induced gingival overgrowth tissues of periodontitis patients},
journal = {Archives of Oral Biology},
year = {2011},
volume = {56},
pages = {277--284},
number = {3},
month = mar,
abstract = {Objectives The purpose of the present study was to analyse transcriptomes
and mRNA expression levels for specific genes in calcium-channel
blocker-induced gingival overgrowth (GO) tissues.Design Eight gingival
tissues samples (from both GO negative and positive sites) were harvested
from four GO patients for microarray analyses. Twelve candidate genes
were selected for further quantitative real time reverse transcription-polymerase
chain reaction (qRT-PCR) analyses. Ten GO tissues from periodontitis
patients and ten control gingival tissues from healthy subjects were
compared by qRT-PCR. Mann-Whitney U-test was used for statistical
evaluation.Results In GO positive tissues, 163-1631 up-regulated
and 100-695 down-regulated genes were identified with more than two-fold
changes compared with GO negative tissues amongst patients by microarray
experiments. No commonly expressed genes amongst the eight sets of
microarray data were found. The clustering analysis confirmed that
the entire transcriptome patterns showed similarities in individuals,
but differences amongst the four patients. The qRT-PCR and statistical
analyses for the candidate genes, though, revealed differential gene
expressions between GO-positive and negative tissues. We found that
matrix metalloproteinase (MMP)-1 and MMP-12 as well as cathepsin-L
were significantly up-regulated whilst keratin-10 and transforming
growth factor-[beta]1 were significantly down-regulated in GO tissues
of periodontitis patients compared with the control gingival tissues
of healthy subjects.Conclusion The microarray analyses revealed that
GO pathogenesis was complex and individually varied, though GO-affected
gingival tissues were controlled at least by genes related to collagen
metabolisms including regulated MMPs, cathepsin-L, growth factors,
and keratins to maintain tissue homeostasis in vivo.},
issn = {0003-9969},
keywords = {Gingival overgrowth, Calcium-channel blocker, Microarray analysis},
url = {http://www.sciencedirect.com/science/article/pii/S0003996910003006}
}
@ARTICLE{Shimo2011,
author = {Shimo, Hugo and Ishimaru, Yasuhiro and An, Gynheung and Yamakawa,
Takashi and Nakanishi, Hiromi and Nishizawa, Naoko K.},
title = {Low cadmium (LCD), a novel gene related to cadmium tolerance and
accumulation in rice},
journal = {J. Exp. Bot.},
year = {2011},
volume = {62},
pages = {5727-5734},
number = {15},
abstract = {The contamination of food crops by cadmium (Cd) is a major concern
in food production because it can reduce crop yields and threaten
human health. In this study, knockout rice plants (Oryza sativa)
tagged with the gene trap vector pGA2707 were screened for Cd tolerance,
and the tolerant line lcd was obtained. The lcd mutant showed tolerance
to Cd on agar plates and in hydroponic culture during early plant
development. Metal concentration measurements in hydroponically grown
plants revealed significantly less Cd in the shoots of lcd plants
compared with wild-type (WT) shoots. When cultured in the field in
soil artificially contaminated with low levels of Cd, lcd showed
no significant difference in the Cd content of its leaf blades; however,
the Cd concentration in the grains was 55% lower in 2009 and 43%
lower in 2010. There were no significant differences in plant dry
weight or seed yield between lcd and wild-type plants. LCD, a novel
gene, is not homologous to any other known gene. LCD localized to
the cytoplasm and nucleus, and was expressed mainly in the vascular
tissues in the roots and phloem companion cells in the leaves. These
data indicate that lcd may be useful for understanding Cd transport
mechanisms and is a promising candidate rice line for use in combating
the threat of Cd to human health.},
doi = {10.1093/jxb/err300},
eprint = {http://jxb.oxfordjournals.org/cgi/reprint/62/15/5727.pdf},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/62/15/5727}
}
@ARTICLE{Shin2011c,
author = {Shin, Bo-Moon and Moon, Se Jin and Kim, You Sun and Shin, Won Chang
and Yoo, Hyeon Mi},
title = {Characterization of Cases of Clostridium difficile Infection (CDI)
Presenting at an Emergency Room: Molecular and Clinical Features
Differentiate Community-Onset Hospital-Associated and Community-Associated
CDI in a Tertiary Care Hospital},
journal = {J. Clin. Microbiol.},
year = {2011},
volume = {49},
pages = {2161-2165},
number = {6},
abstract = {Definition of community-onset, hospital-acquired Clostridium difficile
infection (CO-HA-CDI) is difficult in patients presenting with diarrhea
at hospitals or outpatient clinics, especially 4 to 12 weeks after
the last discharge. We performed C. difficile stool culture for 272
diarrheic patients visiting the emergency room (ER) between January
2006 and June 2010. C. difficile was isolated from 36 cases (13.2%),
and isolation rates increased year by year, from 10.1% in 2008 to
12.4% in 2009 and 16.7% in 2010. Among 32 toxin-positive isolates,
13 (40.6%) and 19 (59.4%) were associated with CO-HA-CDI and community-acquired
CDI (CA-CDI), respectively, if cases with CDI diagnosed within 12
weeks after discharge were considered hospital associated. The majority
(70%) of CO-HA-CDI cases occurred within 2 weeks after hospital discharge,
although the interval from discharge to onset of symptoms was as
long as 10 weeks. We found via tcdA and tcdB and repetitive sequence
PCR analysis, that toxin A-positive/toxin B-positive isolates were
the most prevalent in both CO-HA-CDI (53.8%) and CA-CDI (94.7%) cases.
Toxin A-negative/toxin B-positive isolates were also still highly
associated with HA-CDI cases but were also observed in CA-CDI cases.
Younger age, fewer underlying diseases, lack of prior antibiotic
use, and genetic diversity of isolates in repetitive sequence PCR
were the main characteristics in CA-CDI cases visiting the ER.},
doi = {10.1128/JCM.02330-10},
eprint = {http://jcm.asm.org/cgi/reprint/49/6/2161.pdf},
url = {http://jcm.asm.org/cgi/content/abstract/49/6/2161}
}
@ARTICLE{Shin2009,
author = {Shin, Dong Wook and Kim, Su Nam and Lee, Sang Min and Lee, Woojung
and Song, Min Jeong and Park, Sun Mi and Lee, Tae Ryong and Baik,
Joo-Hyun and Kim, Han Kon and Hong, Jeong-Ho and Noh, Minsoo},
title = {(-)-Catechin promotes adipocyte differentiation in human bone marrow
mesenchymal stem cells through PPAR[gamma] transactivation},
journal = {Biochemical Pharmacology},
year = {2009},
volume = {77},
pages = {125--133},
number = {1},
month = jan,
abstract = {Green tea intake has been shown to confer various health benefits
to patients suffering from metabolic disorders. Here, we studied
the effect of several major green tea polyphenols on adipocyte differentiation
in human bone marrow mesenchymal stem cells (hBM-MSCs) and compared
it to the effect of representative antidiabetic drugs. (-)-Catechin
was the most potent of the eight green tea polyphenols evaluated
in promoting adipocyte differentiation in hBM-MSCs, and this effect
was dose-dependent. (-)-Catechin increased the mRNA levels of various
adipogenic markers, such as adiponectin, peroxisome proliferator-activated
receptor gamma (PPAR[gamma]), FABP4, and LPL, as measured during
adipocyte differentiation in hBM-MSCs. In addition, (-)-catechin
upregulated the secretion of adiponectin in hBM-MSC culture. Using
a reporter gene assay and a competitive ligand binding study, (-)-catechin
also significantly activated PPAR[gamma] in a dose-dependent fashion;
however, (+)-catechin, the enantiomer of (-)-catechin, was not effective
as a PPAR[gamma] agonist, which seems to imply that the effect of
(-)-catechin on PPAR[gamma] is stereospecific. In conclusion, our
data suggest that (-)-catechin promotes adipocyte differentiation
and increased sensitivity to insulin in part by direct activation
of PPAR[gamma], which could be at the basis of the observed pharmacological
benefits of green tea intake in reducing the risk of type 2 diabetes.},
issn = {0006-2952},
keywords = {(-)-Catechin, green tea, Human bone marrow mesenchymal stem cells,
Adipocyte differentiation, PPAR[gamma]},
url = {http://www.sciencedirect.com/science/article/B6T4P-4TKPV9T-2/2/1c83eab06b66678557edac5c4fe19a71}
}
@ARTICLE{Shin2008,
author = {Shin, Dong-Mi and Shaffer, Daniel J. and Wang, Hongsheng and Roopenian,
Derry C. and Morse, Herbert C., III},
title = {NOTCH Is Part of the Transcriptional Network Regulating Cell Growth
and Survival in Mouse Plasmacytomas},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {9202--9211},
number = {22},
month = nov,
abstract = {Aside from Myc-activating translocations characteristic of plasmacytomas
(PCT), little is known about genetic factors and signaling pathways
responsible for the development of spontaneous B-cell lineage lymphomas
of mice. Here, we characterized the transcriptional profiles of PCT,
centroblastic diffuse large B-cell lymphomas (CBL), and high-grade
splenic marginal zone B-cell lymphoma (MZL++) using high-throughput
quantitative reverse transcription-PCR. Expression profiles of CBL
and MZL++ were strikingly similar and quite unlike that of PCT. Among
the genes expressed at significantly higher levels by PCT were a
number involved in NOTCH signaling, a finding supported by gene set
enrichment analyses of microarray data. To investigate the importance
of this pathway, NOTCH signaling was blocked in PCT cell lines by
treatment with a {gamma}-secretase inhibitor (GSI) or transduction
of a dominant-negative mutant of MAML1. These treatments resulted
in reduced expression of NOTCH transcriptional targets in association
with impaired proliferation and increased apoptosis. GSI treatment
of transformed plasma cells in a primary PCT also induced apoptosis.
These results integrate NOTCH activation with oncogenic signaling
pathways downstream of translocated Myc in the pathogenesis of mouse
PCT, two signaling pathways also implicated in development of human
multiple myeloma and T-cell lymphoblastic lymphoma. [Cancer Res 2008;68(22):9202-11]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/22/9202}
}
@ARTICLE{Shin2009a,
author = {Shin, Gi Won and Cho, Yang Sook and Hwang, Hee Sung and Oh, Mi-Hwa
and Nam, Hong Gil and Park, Jin Hyun and Jung, Gyoo Yeol},
title = {A new single-step quantitative pathogen detection system: Template-tagging
followed by multiplex asymmetric PCR using common primers and CE-SSCP},
journal = {ELECTROPHORESIS},
year = {2009},
volume = {30},
pages = {2728--2736},
number = {15},
abstract = {Abstract 10.1002/elps.200900074.abs Rapid diagnosis of bacterial infection
is important for patient management and appropriate therapy during
the early phase of bacteria-induced disease. Among the existing techniques
for identifying microbial, CE-SSCP combined with 16S ribosomal RNA
gene-specific PCR has the benefits of excellent sensitivity, resolution,
and reproducibility. However, even though CE-SSCP can separate PCR
products with high-resolution, multiplex detection and quantification
are complicated by primer-dimer formation and non-specific amplification.
Here, we describe a novel technique for multiplex detection and quantification
of pathogens by template-tagging followed by multiplex asymmetric
PCR and subsequent CE-SSCP. More specifically, we reverse transcribed
16S ribosomal RNAs from seven septicemia-inducing pathogens, tagged
the templates with common end sequences, and amplified them using
common primers. The resulting amplicons could be successfully separated
by CE-SSCP and quantified by comparison to an internal standard.
This method yielded results that illustrate the potential of this
system for diagnosing infectious disease.},
issn = {1522-2683},
keywords = {CE-SSCP, Common primer, Diagnosis, Pathogen, Template-tagging},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200900074}
}
@ARTICLE{Shin2010,
author = {Shin, Gi Won and Hwang, Hee Sung and Nam, Hong Gil and Oh, Mi-Hwa
and Jung, Gyoo Yeol},
title = {Sensitive multiplex RNA quantification using capillary electrophoresis-based
single-strand conformation polymorphism},
journal = {Biotechnol. Bioeng.},
year = {2010},
volume = {106},
pages = {167--172},
number = {1},
abstract = {Abstract 10.1002/bit.22646.abs Quantification of RNA provides information
crucial for various biological studies, including analysis of mRNA
expression and that of microRNAs. Reverse transcription (RT) coupled
with real-time polymerase chain reaction (PCR) is known to be the
most accurate method for quantifying nucleic acids, and thus represents
the state-of-the-art for RNA quantification. However, the use of
real-time PCR for RNA quantification is limited to a single target
per analytical run because of reductions in quantification power
and limitations of fluorescence dyes associated with multiplex applications.
Here, we report a novel multiplex RNA quantification method that
uses capillary electrophoresis single-strand conformation polymorphism
(CE-SSCP) coupled with modified RT and asymmetric PCR. The reverse
transcripts of seven in vitro transcribed RNAs were modified with
common sequence tags and amplified by asymmetric PCR using primers
specific to the common tags. The resulting amplicons were separated
and quantified by CE-SSCP. A series of experiments using different
amounts of RNA demonstrated that the assay had a limit of detection
of 2 amol and a dynamic range of ∼105. These results clearly
indicate the potential of this method to provide robust and precise
multiplex RNA quantification. Biotechnol. Bioeng. 2010; 106: 167–172.
© 2009 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {RNA quantification, multiplex analysis, template tagging, CE-SSCP},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22646}
}
@ARTICLE{Shin2008a,
author = {Shin, Heesun and Hirst, Martin and Bainbridge, Matthew and Magrini,
Vincent and Mardis, Elaine and Moerman, Donald and Marra, Marco and
Baillie, David and Jones, Steven},
title = {Transcriptome analysis for Caenorhabditis elegans based on novel
expressed sequence tags},
journal = {BMC Biology},
year = {2008},
volume = {6},
pages = {30},
number = {1},
abstract = {BACKGROUND:We have applied a high-throughput pyrosequencing technology
for transcriptome profiling of Caenorhabditis elegans in its first
larval stage. Using this approach, we have generated a large amount
of data for expressed sequence tags, which provides an opportunity
for the discovery of putative novel transcripts and alternative splice
variants that could be developmentally specific to the first larval
stage. This work also demonstrates the successful and efficient application
of a next generation sequencing methodology.RESULTS:We have generated
over 30 million bases of novel expressed sequence tags from first
larval stage worms utilizing high-throughput sequencing technology.
We have shown that approximately 14% of the newly sequenced expressed
sequence tags map completely or partially to genomic regions where
there are no annotated genes or splice variants and therefore, imply
that these are novel genetic structures. Expressed sequence tags,
which map to intergenic (around 1000) and intronic regions (around
580), may represent novel transcribed regions, such as unannotated
or unrecognized small protein-coding or non-protein-coding genes
or splice variants. Expressed sequence tags, which map across intron-exon
boundaries (around 300), indicate possible alternative splice sites,
while expressed sequence tags, which map near the ends of known transcripts
(around 600), suggest extension of the coding or untranslated regions.
We have also discovered that intergenic and intronic expressed sequence
tags, which are well conserved across different nematode species,
are likely to represent non-coding RNAs. Lastly, we have incorporated
available serial analysis of gene expression data generated from
first larval stage worms, in order to predict novel transcripts that
might be specifically or predominantly expressed in the first larval
stage.CONCLUSION:We have demonstrated the use of a high-throughput
sequencing methodology to efficiently produce a snap-shot of transcriptional
activities occurring in the first larval stage of C. elegans development.
Such application of this new sequencing technique allows for high-throughput,
genome-wide experimental verification of known and novel transcripts.
This study provides a more complete C. elegans transcriptome profile
and, furthermore, gives insight into the evolutionary and biological
complexity of this organism.},
doi = {10.1186/1741-7007-6-30},
issn = {1741-7007},
pubmedid = {18611272},
url = {http://www.biomedcentral.com/1741-7007/6/30}
}
@ARTICLE{Shin2004,
author = {Shin, Ji Hye and Kim, Tae Soo and Kim, Sang Cheol and Yang, Yeon
Ju and Yang, Sang-Hwa and Kim, In Young and Lee, Gui Youn and Jeung,
Heu-Cheul and Jang, Woo-Ick and Chung, Hyun Cheol and Rha, Sun Young},
title = {Vascular genomics using cDNA microarray for identification of angiogenesis-related
genes in in vivo-mimicking model system.},
journal = {AACR Meeting Abstracts},
year = {2004},
volume = {2004},
pages = {832--},
number = {1},
month = mar,
abstract = {With increasing interests in angiogenesis for understanding the cancer
biology and developing targeted anticancer drugs, there have been
many efforts to elucidate the mechanisms of tumor angiogenesis. However,
there is little known about the molecular mechanisms not only tumor
angiogenesis but also normal angiogenesis. Here, we evaluated the
gene expression profiling of HUVECs in various in vitro culture conditions
mimicking the processes of in vivo angiogenesis; 1) culture without
serum as a negative control, 2) conventional condition with 10% serum
and growth factors, 3) culture upon the matrigel for tube formation,
4) co-culture with YCC-3 gastric cancer cells, and 5) co-culture
with cancer cells upon the matrigel. In addition, we evaluated the
gene expression profiling of YCC-3 human gastric cancer cells and
its in vivo tumor compared to HUVEC, to identify the potential genomic
changes in tumor angiogenesis. We amplified 2 ug of total RNA due
to limited amount of HUVEC, resulting in 1.2-4Kb sized mRNA by Bioanalyzer
(Agilent Inc.), and average 2,000 fold amplification. cDNA microarrays
of 3 replicates for each condition were performed with 17K human
gene chips in reference design with Yonsei common reference RNA with
11 cancer cell lines. Mean correlation coefficient of triplicates
was 0.98{+/-}0.01. Using bootstraping resampling method, we identified
sets of genes specific for each condition; 1) 627 up-regulated and
502 down-regulated genes compared to inert HUVEC, 2) 199 genes related
to tube formation, 3) 247 genes related to activated HUVEC from co-culture
with cancer cell line, and 5) 81 genes related to in vivo mimicking
cultures. In addition, after we observed the difference between HUVEC
and YCC-3 cancer cells with 329 differentially expressed genes, we
identified 352 in vivo angiogenesis related genes with 127 known
various biological functions including notch homolog 3, ephrin-B2,
apoptosis inhibitor-4, EGFR and Cyclin B1. When we evaluated the
changes of several protease and known angiogenic molecules such as
MMP-2 or MT1-MMP at each condition, we observed that the difference
of expression is significant between in vitro and in vivo condition.
We confirmed that our RNA amplification system is stable and reliable
for microarray hybridization and could identify the gene sets related
to HUVEC activation which might function significantly for angiogenesis.
Based on the comparison between in vitro and in vivo experiments,
we could identify the significant gene sets related to the cross
talk between tumor cells and the host stromal cells. In conclusion,
we suggest that the well-designed experiment based on the biological
information with clear objective is one of the most significant point
to consider in microarray.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/832}
}
@ARTICLE{Shin2009b,
author = {Shin, Jennifer H. and Shin, Dong Wook and Noh, Minsoo},
title = {Interleukin-17A inhibits adipocyte differentiation in human mesenchymal
stem cells and regulates pro-inflammatory responses in adipocytes},
journal = {Biochemical Pharmacology},
year = {2009},
volume = {77},
pages = {1835--1844},
number = {12},
month = jun,
abstract = {The immune system is closely linked to human metabolic diseases. Serum
levels of IL-6 increase with obesity and insulin resistance. Not
only does IL-6 decrease the insulin sensitivity of human cells such
as adipocytes, but it also regulates the lineage commitment of naïve
T cells into interleukin (IL)-17A-producing CD4(+) T (Th17) cells.
Although IL-17A exerts a variety of effects on somatic tissues, its
functional role in human adipocytes has not been identified. In this
work, we show that IL-17A inhibits adipocyte differentiation in human
bone marrow mesenchymal stem cells (hBM-MSCs), while promoting lipolysis
of differentiated adipocytes. We find that IL-17A increases both
mRNA and protein secretion of IL-6 and IL-8 during adipocyte differentiation
in hBM-MSCs. IL-17A up-regulates cyclooxygenase (COX)-2 gene expression
and thereby increases the level of prostaglandin (PG) E2 in differentiated
adipocyes. The suppression of anti-adipogenic PGE2 by COX inhibitors
such as aspirin and NS-398 partially blocked the effect of IL-17A
on adipocyte differentiation in hBM-MSCs. Therefore, IL-17A exhibits
its inhibitory effect in part via the COX-2 induction in differentiated
adipocytes. In addition, treatment with anti-IL-17A antibody neutralizes
IL-17A-mediated effects on adipocyte differentiation and function.
These results suggest that IL-17A plays a regulatory role in both
the metabolic and inflammatory processes of human adipocytes, similar
to other pro-inflammatory cytokines such as IL-1, IFN[gamma], and
TNF[alpha].},
issn = {0006-2952},
keywords = {IL-17A, Metabolic syndromes, Inflammation, Adipocyte differentiation,
Human bone marrow mesenchymal stem cells},
url = {http://www.sciencedirect.com/science/article/B6T4P-4VW551G-3/2/1a384deebf80e6c5420619990d626505}
}
@ARTICLE{Shin2008b,
author = {Shin, Jay W. and Huggenberger, Reto and Detmar, Michael},
title = {Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic
endothelium reveals endothelial-specific molecule-1 as a novel mediator
of lymphangiogenesis},
journal = {Blood},
year = {2008},
volume = {112},
pages = {2318--2326},
number = {6},
month = sep,
abstract = {Lymphatic vessel growth and activation, mediated by vascular endothelial
growth factor (VEGF)-C and/or VEGF-A, have important roles in metastasis
and in chronic inflammation. We aimed to comprehensively identify
downstream molecular targets induced by VEGF-A or VEGF-C in lymphatic
endothelium by analyzing the time-series transcriptional profile
of treated human dermal lymphatic endothelial cells (LECs). We identified
a number of genes, many not previously known to be involved in lymphangiogenesis,
that were characterized either as early response genes, transiently
induced genes, or progressively induced genes. Endothelial-specific
molecule-1 (ESM-1) was one of the genes that were most potently induced
by both VEGF-A and VEGF-C. Whereas ESM-1 induction by VEGF-A was
mainly dependent on activation of VEGFR-2, VEGF-C-mediated induction
depended on the activity of both VEGFR-2 and VEGFR-3. Incubation
of LECs with ESM-1 increased the stimulatory effects of both VEGF-A
and VEGF-C on LEC proliferation and migration, whereas ESM-1 alone
had no effect. Importantly, VEGF-A (or VEGF-C) induction of LEC proliferation
and migration were significantly inhibited by siRNA-mediated silencing
of ESM-1 in vitro and in vivo. These studies reveal ESM-1 as a novel
mediator of lymphangiogenesis and as a potential target for the inhibition
of pathologic lymphatic vessel activation.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/6/2318}
}
@ARTICLE{Shin2011b,
author = {Shin, Nara and You, Kwon Tae and Lee, Hanna and Kim, Won Kyu and
Song, Meiying and Choi, Hee-Jung and Rhee, Hwanseok and Nam, Suk
Woo and Kim, Hoguen},
title = {Identification of frequently mutated genes with relevance to nonsense
mediated mRNA decay in the high microsatellite instability cancers},
journal = {International Journal of Cancer},
year = {2011},
volume = {128},
pages = {2872--2880},
number = {12},
abstract = {Abstract Frameshift mutations at coding mononucleotide repeats (cMNR)
are frequent in high-microsatellite instability (MSI-H) cancers.
Frameshift mutations in cMNR result in the formation of a premature
termination codon (PTC) in the transcribed mRNA, and these abnormal
mRNAs are generally degraded by nonsense mediated mRNA decay (NMD).
We have identified novel genes that are frequently mutated at their
cMNR by blocking NMD in two MSI-H cancer cell lines. After blocking
NMD, we screened for differentially expressed genes using DNA microarrays,
and then used database analysis to select 28 candidate genes containing
cMNR with more than 9 nucleotide repeats. cMNR mutations have not
been previously reported in MSI-H cancers for 15 of the 28 genes.
We analyzed the cMNR mutation of each of the 15 genes in 10 MSI-H
cell lines and 21 MSI-H cancers, and found frequent mutations of
12 genes in MSI-H cell lines and cancers, but not in microsatellite
stable (MSS) cancers. Among these genes, the most frequently mutated
in MSI-H cell lines were MLL3 (70%), PHACTR4 (70%), RUFY2 (50%) and
TBC1D23 (50%). MLL3, which has already been implicated in cancer,
had the highest mutation frequency in MSI-H cancers (48%). Our combined
approach of NMD block, database search, and mutation analysis has
identified a large number of genes mutated in their cMNR in MSI-H
cancers. The identified mutations are expected to contribute to MSI-H
tumorigenesis by causing an absence of gene expression or low gene
dosage effects.},
doi = {10.1002/ijc.25641},
issn = {1097-0215},
keywords = {MSI-H cancers, NMD, coding mononucleotide repeats, frameshift mutation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25641}
}
@ARTICLE{Shin2011,
author = {Shin, Seung-Hun and Shin, Gi Won and Yim, Seon-Hee and Jung, Seung-Hyun
and Jung, Gyoo Yeol and Chung, Yeun-Jun},
title = {Strategy for high-fidelity multiplex DNA copy number assay system
using capillary electrophoresis devices},
journal = {ELECTROPHORESIS},
year = {2011},
volume = {32},
pages = {1837--1843},
number = {14},
abstract = {Structural variation of human genome such as duplications and deletions,
collectively termed copy number variation (CNV), is one of the major
genetic variations. Reliable and efficient measurement of CNV will
be essential to develop diagnostic tools for CNV-related diseases.
We established a strategy based on multiplex PCR and capillary electrophoresis
(CE) for reliable CNV assay. Multiplex-PCR was performed using five
primer sets for target loci and a diploid control (DC). We designed
primers satisfying three conditions: different size of each PCR product
for CE separation, unified annealing temperature for multiplex PCR,
and suitability for quantitative PCR (qPCR). We defined the accurate
PCR cycles for quantification of copy numbers at which the amplifications
for all targets were supposed to be exponential, named maximum doubling
cycle. CE was carried out with PCR product and the ratio of the peak
areas (target/diploid control) was calculated. Our multiplex PCR-CE
analysis reliably determined copy numbers of X chromosome with variable
copies ranging from 1 to 5 and showed higher reliability than qPCR
(correlation coefficient 0.996 versus 0.898). When measuring the
six randomly selected autosomal CNV targets using our multiplex PCR-CE,
the results agreed with those from qPCR. In addition, our strategy
was validated for the broad application to commonly used CE devices.
Taken together, this assay will be useful for accurate analysis of
multiple disease-associated CNVs in a clinical setting.},
doi = {10.1002/elps.201100093},
issn = {1522-2683},
keywords = {Copy number variation, Maximum doubling cycle, Multiplex PCR-CE analysis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.201100093}
}
@ARTICLE{Shin2011a,
author = {Shin, Su-Kyung and Ha, Tae-Youl and McGregor, Robin A. and Choi,
Myung-Sook},
title = {Long-term curcumin administration protects against atherosclerosis
via hepatic regulation of lipoprotein cholesterol metabolism},
journal = {Molecular Nutrition \& Food Research},
year = {2011},
volume = {55},
pages = {1829--1840},
number = {12},
abstract = {Scope: Atherosclerosis is a major cause of cardiovascular disease
caused by high cholesterol. Stains are widely prescribed to lower
cholesterol levels, but natural dietary compounds may also be effective.
Therefore, we studied the effect of the natural dietary compound
curcumin on atherosclerosis and its underlying mechanisms based on
plasma and hepatic lipid metabolism.Methods and results: LDLR−/−
mice were fed a high-cholesterol diet and treated with curcumin,
lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections
revealed curcumin ameliorated early atherosclerotic lesions, lipid
infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin
treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides,
LDL cholesterol and Apo B levels as well as CETP activity, while
curcumin increased plasma HDL cholesterol and liver Apo A-I expression,
similar to lovastatin treatment. Curcumin caused transcriptional
inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression.
Hepatic PPARα and LXRα expression was upregulated by curcumin treatment.
Hepatic complement factor D (Cfd) and systemic CRP levels, markers
of immune complement pathway activation, were significantly reduced
by curcumin treatment.Conclusion: Long-term curcumin treatment lowers
plasma and hepatic cholesterol and suppresses early atherosclerotic
lesions comparable to the protective effects of lovastatin. The anti-atherogenic
effect of curcumin is mediated via multiple mechanisms including
altered lipid, cholesterol and immune gene expression.},
doi = {10.1002/mnfr.201100440},
issn = {1613-4133},
keywords = {Atherosclerosis, Curcumin, Gene expression, HMG-CoA, Lovastatin},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/mnfr.201100440}
}
@ARTICLE{Shinmura2004,
author = {Shinmura, Kazuya and Tao, Hong and Goto, Masanori and Igarashi, Hisaki
and Taniguchi, Terumi and Maekawa, Masato and Takezaki, Toshiro and
Sugimura, Haruhiko},
title = {Inactivating mutations of the human base excision repair gene NEIL1
in gastric cancer},
journal = {Carcinogenesis},
year = {2004},
volume = {25},
pages = {2311--2317},
number = {12},
month = dec,
abstract = {Oxidized DNA base lesions, such as thymine glycol (Tg) and 8-hydroxyguanine,
are often toxic and mutagenic and have been implicated in carcinogenesis.
To clarify whether NEIL1 protein, which exhibits excision repair
activity towards such base lesions, is involved in gastric carcinogenesis,
we examined 71 primary gastric cancers from Japanese patients and
four gastric cancer cell lines for mutations and genetic polymorphisms
of the NEIL1 gene. We also examined 20 blood samples from Chinese
patients for NEIL1 genetic polymorphisms. Three mutations (c.82_84delGAG:p.Glu28del,
c.936G > A and c.1000A > G:p.Arg334Gly) and two genetic polymorphisms
were identified. When the excision repair activity towards double-stranded
oligonucleotide containing a Tg:A base pair was compared among six
types of recombinant NEIL1 proteins, p.Glu28del-type NEIL1, found
in a primary case, was found to exhibit an extremely low activity
level. Moreover, c.936G > A, located in the last nucleotide of exon
10 and detected in the KATO-III cell line, was shown to be associated
with a splicing abnormality using an in vivo splicing assay. An immunofluorescence
analysis showed that the wild-type NEIL1 protein, but not the truncated
protein encoded by the abnormal transcript arising from the c.936G
> A mutation, was localized in the nucleus, suggesting that the truncated
protein is unlikely to be capable of repairing nuclear DNA. An expression
analysis revealed that NEIL1 mRNA expression was reduced in six of
13 (46%) primary gastric cancer specimens that were examined. These
results suggest that low NEIL1 activities arising from mutations
and reduced expression may be involved in the pathogenesis in a subset
of gastric cancers.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/25/12/2311}
}
@ARTICLE{Shinmura2004a,
author = {Shinmura, Kazuya and Tao, Hong and Yamada, Hidetaka and Kataoka,
Hideki and Sanjar, Ravshanov and Wang, Jiandong and Yoshimura, Kimio
and Sugimura, Haruhiko},
title = {Splice-site genetic polymorphism of the human kallikrein 12 (KLK12)
gene correlates with no substantial expression of KLK12 protein having
serine protease activity},
journal = {Hum. Mutat.},
year = {2004},
volume = {24},
pages = {273--274},
number = {3},
abstract = {Abstract 10.1002/humu.9270.abs The human kallikrein 12 (KLK12) gene
is a new member of the KLK gene family, some members of which are
implicated in the initiation and progression of cancer. In this study,
we examined 50 non-cancerous tissues from Japanese patients with
primary gastric cancer to determine the presence of genetic polymorphisms
in the KLK12 gene using polymerase chain reaction (PCR)-single-strand
conformation polymorphism and sequencing. Four different types of
genetic polymorphisms were identified: one at a splice-donor site
of intron 4 (c.457+2T>C), two in exon 6 (c.618_619delTG:p.Cys206fsX72
and c.735G>A:p.Met245Ile), and one in intron 3. The c.457+2T>C polymorphism
was observed at a high frequency (allele frequency:0.63), compared
to the frequencies of the two polymorphisms in exon 6 (allele frequency:0.01).
Reverse transcriptase (RT)-PCR and Western blot analyses revealed
that the c.457+2T>C polymorphism was associated with a splicing abnormality
and that the expression of the human KLK12 protein (hK12), corresponding
to the putative serine protease, was absent in individuals with a
c.457+2C/C genotype but not in individuals with the T/T or T/C genotypes.
We also found that recombinant His6-tagged hK12 has activity that
cleaves chromogenic substrate (H-D-Pro-L-Phe-L-Arg-p-nitroaniline
dihydrochloride), that is, serine protease activity. These results
indicate that individuals with the c.457+2C/C genotype have no substantial
expression of hK12 serine protease. © 2004 Wiley-Liss, Inc.},
issn = {1098-1004},
keywords = {splice site, genetic polymorphism, kallikrein, serine protease, gastric
cancer, KLK12},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.9270}
}
@ARTICLE{Shinohara2011,
author = {Shinohara, Yoshiaki and Yahagi, Kazuko and Kawano, Mitsuoki and Nishiyori,
Hiromi and Kawazu, Chika and Suzuki, Naoko and Manabe, Ri-ichiroh
and Hirase, Hajime},
title = {miRNA profiling of bilateral rat hippocampal CA3 by deep sequencing},
journal = {Biochemical and Biophysical Research Communications},
year = {2011},
volume = {409},
pages = {293-298},
abstract = {MicroRNAs (miRNAs) have been demonstrated to be potent post-trascriptional
modulators of protein expression. miRNA expression was profiled in
the left and right dorsal hippocampal CA3 of mature rats by high-throughput
deep sequencing. Among the sequenced and cross-mapped small RNAs,
88% belonged to the miRNAs annotated in the miRBase 15 database.
Nearly half of the small RNAs belonged to the let-7 family miRNA.
Seven percent of the sequenced small RNAs were not annotated in miRBase
15. Bioinformatic analysis of the unannotated small RNA sequences
suggested that seventeen novel miRNA candidates with relatively high
expression levels (>100 tags per million). The left:right expression
ratios were similar for all highly expressed miRNAs with less than
10% differences. These results provide a basic idea of the relative
expression strengths of known and unknown miRNAs in the dorsal hippocampal
CA3.},
issn = {0006-291X},
keywords = {Deep sequencing, Hippocampus, Left-right asymmetry, Let-7},
url = {http://www.sciencedirect.com/science/article/pii/S0006291X1100756X}
}
@ARTICLE{Shinojima2010,
author = {Shinojima, Yui and Terui, Tadashi and Hara, Hiroyuki and Kimura,
Makoto and Igarashi, Jun and Wang, Xiaofei and Kawashima, Hiroyuki
and Kobayashi, Yujin and Muroi, Satomi and Hayakawa, Satoshi and
Esumi, Mariko and Fujiwara, Kyoko and Ghosh, Srimoyee and Yamamoto,
Tatsuo and Held, William and Nagase, Hiroki},
title = {Identification and analysis of an early diagnostic marker for malignant
melanoma: ZAR1 intra-genic differential methylation},
journal = {J Dermatol Sci},
year = {2010},
volume = {59},
pages = {98--106},
number = {2},
month = aug,
abstract = {Epigenetic changes such as aberrant DNA methylation and histone modification
have been shown to play an important role in the tumorigenesis of
malignant melanoma. To identify novel tumor-specific differentially
methylated regions (DMRs) in human malignant melanoma. The aberrant
methylation at 14 candidate human genomic regions identified through
a mouse model study with quantitative DNA methylation analysis using
the Sequenom MassARRAY system was performed. The CpG island Exon
1 region of the Zygote arrest 1 (ZAR1) gene, which is responsible
for oocyte-to-embryo transition, showed frequent aberrant methylation
of 28 out of 30 (93%) melanoma surgical specimens, 16 of 17 (94%)
melanoma cell lines, 0% of 4 normal human epidermal melanocyte (NHEM)
cell lines, 0% of 10 melanocytic nevi and 100% of 51 various cancer
cell lines. According to the real-time RT-PCR, the ZAR1 gene was
overexpressed in part of the hypermethylated cell lines, while its
low expression with bivalent histone methylation status was seen
in unmethylated cell lines. Our findings suggest that the ZAR1 intra-genic
differentially methylated region would be a useful tumor marker for
malignant melanoma and may be other type of cancers. The involvement
of ZAR1 in the carcinogenesis of melanoma, still remains unclear,
although we have examined tumorigenic capacities by exogenous full-length
ZAR1 over-expression and siRNA knock-down experiments.},
issn = {0923-1811},
keywords = {Malignant melanoma, Aberrant methylation, Zygote arrest 1 (ZAR1),
Differentially methylated regions (DMRs)},
publisher = {Elsevier,},
refid = {S0923-1811(10)00158-1},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0923181110001581?showall=true}
}
@ARTICLE{Shinozawa2009,
author = {Shinozawa, Tadahiro and Tsuji, Akiko and Imahashi, Kenichi and Nakashima,
Kosuke and Sawada, Hiroshi and Toyoshiba, Hiroyoshi and Yamamoto,
Satoshi and Takami, Kenji and Imai, Ryoetsu},
title = {Gene Expression Profiling of Functional Murine Embryonic Stem Cell-Derived
Cardiomyocytes and Comparison with Adult Heart: Profiling of Murine
ESC-Derived Cardiomyocytes},
journal = {J Biomol Screen},
year = {2009},
volume = {14},
pages = {239--245},
number = {3},
month = mar,
abstract = {Although embryonic stem cell (ESC)--derived cardiomyocytes may be
a powerful tool in drug discovery, their potential has not yet been
fully explored. Nor has a detailed comparison with adult heart tissue
been performed. We have developed a method for efficient production
of cardiomyocyte-rich embryoid bodies (EBs) from murine ESCs. Analysis
of global gene expression profiles showed that EBs on day 7 and/or
21 of differentiation (d7CMs and d21CMs, respectively) were similar
to adult heart tissue for genes categorized as regulators of muscle
contraction or voltage-gated ion channel activity, although d21CMs
were more mature than d7CMs for contractile components related to
morphological structures. Calcium and sodium channel blockers altered
Ca2+ transients, and isoproterenol, a {beta}-adrenergic compound,
increased the rate of beating in d7CMs and d21CMs. Our gene analytic
system therefore enabled us to identify genes that are expressed
in the physiological pathways associated with ion channels and structural
components in d7CMs and d21CMs. We conclude that EBs might be of
use for the basic screening of drugs that might affect contractile
function through ion channels. (Journal of Biomolecular Screening
2009:239-245)},
url = {http://jbx.sagepub.com/cgi/content/abstract/14/3/239}
}
@ARTICLE{Shioya2010,
author = {Shioya, M. and Obayashi, S. and Tabunoki, H. and Arima, K. and Saito,
Y. and Ishida, T. and Satoh, J.},
title = {Aberrant microRNA expression in the brains of neurodegenerative diseases:
miR-29a decreased in Alzheimer disease brains targets neurone navigator
3},
journal = {Neuropathology and Applied Neurobiology},
year = {2010},
volume = {36},
pages = {320--330},
number = {4},
abstract = {M. Shioya, S. Obayashi, H. Tabunoki, K. Arima, Y. Saito, T. Ishida
and J. Satoh (2010) Neuropathology and Applied Neurobiology36, 320–330
Aberrant microRNA expression in the brains of neurodegenerative diseases:
miR-29a decreased in Alzheimer disease brains targets neurone navigator
3 Aims: MicroRNAs (miRNAs) are small non-coding RNAs that regulate
translational repression of target mRNAs. Accumulating evidence indicates
that various miRNAs, expressed in a spatially and temporally controlled
that manner in the brain plays a key role in neuronal development.
However, at present, the pathological implication of aberrant miRNA
expression in neurodegenerative events remains largely unknown. To
identify miRNAs closely associated with neurodegeneration, we performed
miRNA expression profiling of brain tissues of various neurodegenerative
diseases. Methods: We initially studied the frontal cortex derived
from three amyotrophic lateral sclerosis patients by using a microarray
of 723 human miRNAs. This was followed by enlargement of study population
with quantitative RT-PCR analysis (n = 21). Results: By microarray
analysis, we identified up-regulation of miR-29a, miR-29b and miR-338-3p
in amyotrophic lateral sclerosis brains, but due to a great interindividual
variation, we could not validate these results by quantitative RT-PCR.
However, we found significant down-regulation of miR-29a in Alzheimer
disease (AD) brains. The database search on TargetScan, PicTar and
miRBase Target identified neurone navigator 3 (NAV3), a regulator
of axon guidance, as a principal target of miR-29a, and actually
NAV3 mRNA levels were elevated in AD brains. MiR-29a-mediated down-regulation
of NAV3 was verified by the luciferase reporter assay. By immunohistochemistry,
NAV3 expression was most evidently enhanced in degenerating pyramidal
neurones in the cerebral cortex of AD. Conclusions: These observations
suggest the hypothesis that underexpression of miR-29a affects neurodegenerative
processes by enhancing neuronal NAV3 expression in AD brains.},
issn = {1365-2990},
keywords = {Alzheimer disease, bioinformatics, microarray, miR-29a, neurone navigator
3, real-time RT-PCR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2990.2010.01076.x}
}
@ARTICLE{Shiozaki2011,
author = {Shiozaki, Atsushi and Lodyga, Monika and Bai, Xiao-Hui and Nadesalingam,
Jeya and Oyaizu, Takeshi and Winer, Daniel and Asa, Sylvia L. and
Keshavjee, Shaf and Liu, Mingyao},
title = {XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth},
journal = {The American Journal of Pathology},
year = {2011},
volume = {178},
pages = {391--401},
number = {1},
month = jan,
abstract = {Adaptor proteins with multimodular structures can participate in the
regulation of various cellular functions. We have cloned a novel
adaptor protein, XB130, which binds the p85[alpha] subunit of phosphatidyl
inositol 3-kinase and subsequently mediates signaling through RET/PTC
in TPC-1 thyroid cancer cells. In the present study, we sought to
determine the role of XB130 in the tumorigenesis in vivo and in related
molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130
using small interfering RNA inhibited G1-S phase progression, induced
spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic
stimulus-induced cell death. Growth of tumors in nude mice formed
from XB130 shRNA stably transfected WRO cells were significantly
reduced, with decreased cell proliferation and increased apoptosis.
Microarray analysis identified 246 genes significantly changed in
XB130 shRNA transfected cells. Among them, 57 genes are related to
cell proliferation or survival, including many transcription regulators.
Ingenuity Pathway Analysis showed that the top-ranked disease related
to XB130 is cancer, and the top molecular and cellular functions
are cellular growth and proliferation and cell cycle. A human thyroid
tissue microarray study identified expression of XB130 in normal
thyroid tissue as well as in human thyroid carcinomas. These observations
suggest that the expression of XB130 in these cancer cells may affect
cell proliferation and survival by controlling the expression of
multiple genes, especially transcription regulators.},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944010000702}
}
@ARTICLE{Shiraishi2004,
author = {Shiraishi, Munehiro and Harris, R. Adron},
title = {Effects of Alcohols and Anesthetics on Recombinant Voltage-Gated
Na+ Channels},
journal = {J. Pharmacol. Exp. Ther.},
year = {2004},
volume = {309},
pages = {987--994},
number = {3},
month = jun,
abstract = {Voltage-gated Na+ channels (Na+ channels) mediate the rising phase
of action potentials in neurons and excitable cells. Nine subtypes
of the {alpha} subunit (Nav1.1-Nav1.9) have been shown to form functional
Na+ channels to date. Recently, anesthetic concentrations of volatile
anesthetics and ethanol were reported to inhibit Na+ channel functions,
but it is not known whether all subtypes are inhibited by anesthetics.
To investigate possible subtype-specific effects of anesthetics on
Na+ channels, mRNA of Nav1.2, Nav1.4, Nav1.6, and Nav1.8 {alpha}
subunit-encoded genes were injected individually or together with
a {beta} subunit mRNA into Xenopus oocytes. Na+ currents were recorded
using the two-electrode voltage-clamp technique. Isoflurane, at clinically
relevant concentrations, inhibited the currents produced by Nav1.2,
Nav1.4, and Nav1.6 by [~]10% at the holding potential of -90 mV and
by [~]30% at -60 mV, but it did not affect the Nav1.8-mediated current.
An anesthetic fluorocyclobutane (1-chloro-1,2,2-trifluorocyclobutane)
also inhibited the Nav1.2 channel, whereas the nonanesthetic fluorocyclobutane
(1,2-dichlorohexafluorocyclobutane) had no effect. The perfluorinated
heptanol [CF3(CF2)5CH2OH], which produces anesthesia, inhibited the
Nav1.2 channel like other alcohols tested (ethanol, heptanol, and
CF3CH2OH), even though this compound does not affect GABA, glycine,
{alpha}-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, or kainate
receptors. In contrast, most intravenous anesthetics did not have
significant effects on the Nav1.2 channel at clinically relevant
concentrations although urethane inhibited. These results show that
isoflurane inhibits the Na+ channel functions except Nav1.8 in a
voltage-dependent manner. These findings indicate that the Na+ channel
is a neuronal target for anesthetic action.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/309/3/987}
}
@ARTICLE{Shirasawa2010,
author = {Shirasawa, Y. and Shibahara-Sone, H. and Iino, T. and Ishikawa, F.},
title = {Bifidobacterium bifidum BF-1 suppresses Helicobacter pylori-induced
genes in human epithelial cells},
journal = {J Dairy Sci},
year = {2010},
volume = {93},
pages = {4526--4534},
number = {10},
month = oct,
abstract = {Helicobacter pylori infection alters gene expression in host cells.
Specifically, inflammatory chemokines such as IL-8 are upregulated
in the gastric mucosa during H. pylori infection. Although the mechanism
by which H. pylori causes inflammation of the gastric mucosa is not
yet understood, many studies have suggested that nuclear factor kappa
B (NF-κB) plays a key regulatory role in host cells. We have shown
that preincubation with Bifidobacterium bifidum strain BF-1, a probiotic
strain known to improve H. pylori-associated gastritis, suppresses
induction of IL-8 by the pathogen. To investigate how how BF-1 affects
gene expression in H. pylori-infected cells, we performed microarray
analysis to assess gene expression in epithelial cells, which had
been preincubated with BF-1 and infected with H. pylori. We found
that preincubation with BF-1 suppresses the expression of H. pylori-induced
genes in human cells and that most of the affected genes are related
to the NF-κB signaling pathways. These results suggest that BF-1
can affect the regulatory mechanism of the NF-κB signaling pathways.},
issn = {0022-0302},
keywords = {Bifidobacterium bifidum, Helicobacter pylori, probiotics},
publisher = {American Dairy Science Association},
refid = {S0022-0302(10)00483-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0022030210004832?showall=true}
}
@ARTICLE{Shiroguchi2012,
author = {Shiroguchi, Katsuyuki and Jia, Tony Z. and Sims, Peter A. and Xie,
X. Sunney},
title = {Digital RNA sequencing minimizes sequence-dependent bias and amplification
noise with optimized single-molecule barcodes},
journal = {PNAS},
year = {2012},
pages = {1118018109},
abstract = {RNA sequencing (RNA-Seq) is a powerful tool for transcriptome profiling,
but is hampered by sequence-dependent bias and inaccuracy at low
copy numbers intrinsic to exponential PCR amplification. We developed
a simple strategy for mitigating these complications, allowing truly
digital RNA-Seq. Following reverse transcription, a large set of
barcode sequences is added in excess, and nearly every cDNA molecule
is uniquely labeled by random attachment of barcode sequences to
both ends. After PCR, we applied paired-end deep sequencing to read
the two barcodes and cDNA sequences. Rather than counting the number
of reads, RNA abundance is measured based on the number of unique
barcode sequences observed for a given cDNA sequence. We optimized
the barcodes to be unambiguously identifiable, even in the presence
of multiple sequencing errors. This method allows counting with single-copy
resolution despite sequence-dependent bias and PCR-amplification
noise, and is analogous to digital PCR but amendable to quantifying
a whole transcriptome. We demonstrated transcriptome profiling of
Escherichia coli with more accurate and reproducible quantification
than conventional RNA-Seq.},
doi = {10.1073/pnas.1118018109},
eprint = {http://www.pnas.org/cgi/reprint/1118018109v1.pdf},
url = {http://www.pnas.org/cgi/content/abstract/1118018109v1}
}
@ARTICLE{Shiroyanagi2007,
author = {Shiroyanagi, Yoshiyuki and Liu, Benchun and Cao, Mei and Agras, Koray
and Li, Jiang and Hsieh, Michael H. and Willingham, Emily J. and
Baskin, Laurence S.},
title = {Urothelial sonic hedgehog signaling plays an important role in bladder
smooth muscle formation},
journal = {Differentiation},
year = {2007},
volume = {75},
pages = {968--977},
number = {10},
month = dec,
abstract = {During bladder development, primitive mesenchyme differentiates into
smooth muscle (SM) under the influence of urothelium. The gene(s)
responsible for this process have not been elucidated. We propose
that the Sonic hedgehog (Shh) signaling pathway is critical in bladder
SM formation. Herein, we examine the role of the Shh-signaling pathway
during SM differentiation in the embryonic mouse bladder. Genes in
the Shh pathway and SM expression in mouse embryonic (E) bladders
(E12.5, 13.5, and 14.5) were examined by immunohistochemistry (IHC),
in situ hybridization, and reverse transcription polymerase chain
reaction (RT-PCR). To examine the effects of disrupting Shh signaling,
bladder tissues were isolated at E12.5 and E14.5, that is, before
and after bladder SM induction. The embryonic bladders were cultured
on membranes floating on medium with and without 10[thin space][mu]M
of cyclopamine, an Shh inhibitor. After 3 days, SM expression was
examined by assessing the following: SM [alpha]-actin (SMAA), SM
[gamma]-actin (SMGA), SM-myosin heavy chain (SM-MHC), Patched, GLI1,
bone morphogenic protein 4 (BMP4), and proliferating cell nuclear
antigen (PCNA) by IHC and RT-PCR. SM-related genes and proteins were
not expressed in E12.5 mouse embryonic bladder before SM differentiation,
but were expressed by E13.5 when SM differentiation was initiated.
Shh was expressed in the urothelium in E12.5 bladders. Shh-related
gene expression at E12.5 was significantly higher than at E14.5.
In cyclopamine-exposed cultures of E12.5 tissue, SMAA, SMGA, GLI1,
and BMP4 gene expression was significantly decreased compared with
controls, but PCNA gene expression did not change. In cyclopamine-exposed
E14.5 cultures, SMGA and SM-MHC gene expression did not change compared
with controls. Using an in vitro embryonic bladder culture model,
we were able to define the kinetics of SM- and Shh-related gene expression.
Cyclopamine inhibited detrusor SM actin induction, but did not inhibit
SM-MHC induction. SMAA and SMGA genes appear to be induced by Shh-signaling
pathways, but the SM-MHC gene is not. Based on Shh expression by
urothelium and the effects of Shh inhibition on bladder SM induction,
we hypothesize that urothelial-derived Shh orchestrates induction
of SM in the fetal mouse bladder.},
issn = {0301-4681},
keywords = {bladder, smooth muscle, sonic hedgehog, organ culture, development},
url = {http://www.sciencedirect.com/science/article/B983X-4XR8XKR-8/2/a9456880dbb17a2086f48e70cdd3712b}
}
@ARTICLE{Shirra2008,
author = {Shirra, Margaret K. and McCartney, Rhonda R. and Zhang, Chao and
Shokat, Kevan M. and Schmidt, Martin C. and Arndt, Karen M.},
title = {A Chemical Genomics Study Identifies Snf1 as a Repressor of GCN4
Translation},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {35889--35898},
number = {51},
month = dec,
abstract = {The Saccharomyces cerevisiae Snf1 kinase plays a critical role in
recalibrating cellular metabolism in response to glucose depletion.
Hundreds of genes show changes in expression levels when the SNF1
gene is deleted. However, cells can adapt to the absence of a specific
gene when grown in long term culture. Here we apply a chemical genetic
method to rapidly and selectively inactivate a modified Snf1 kinase
using a pyrazolopyrimidine inhibitor. By allowing cells to adjust
to a change in carbon source prior to inhibition of the Snf1 kinase
activity, we identified a set of genes whose expression increased
when Snf1 was inhibited. Prominent in this set are genes that are
activated by Gcn4, a transcriptional activator of amino acid biosynthetic
genes. Deletion of Snf1 increased Gcn4 protein levels without affecting
its mRNA levels. The increased Gcn4 protein levels required the Gcn2
kinase and Gcn20, regulators of GCN4 translation. These data indicate
that Snf1 functions upstream of Gcn20 to regulate control of GCN4
translation in S. cerevisiae.},
url = {http://www.jbc.org/cgi/content/abstract/283/51/35889}
}
@ARTICLE{Shivaprasad2008,
author = {Shivaprasad, Padubidri V. and Rajeswaran, Rajendran and Blevins,
Todd and Schoelz, James and Meins, Frederick, Jr and Hohn, Thomas
and Pooggin, Mikhail M.},
title = {The CaMV transactivator/viroplasmin interferes with RDR6-dependent
trans-acting and secondary siRNA pathways in Arabidopsis},
journal = {Nucleic Acids Res.},
year = {2008},
volume = {36},
pages = {5896--5909},
number = {18},
month = oct,
abstract = {Several RNA silencing pathways in plants restrict viral infections
and are suppressed by distinct viral proteins. Here we show that
the endogenous trans-acting (ta)siRNA pathway, which depends on Dicer-like
(DCL) 4 and RNA-dependent RNA polymerase (RDR) 6, is suppressed by
infection of Arabidopsis with Cauliflower mosaic virus (CaMV). This
effect was associated with overaccumulation of unprocessed, RDR6-dependent
precursors of tasiRNAs and is due solely to expression of the CaMV
transactivator/viroplasmin (TAV) protein. TAV expression also impaired
secondary, but not primary, siRNA production from a silenced transgene
and increased accumulation of mRNAs normally silenced by the four
known tasiRNA families and RDR6-dependent secondary siRNAs. Moreover,
TAV expression upregulated DCL4, DRB4 and AGO7 that mediate tasiRNA
biogenesis. Our findings suggest that TAV is a general inhibitor
of silencing amplification that impairs DCL4-mediated processing
of RDR6-dependent double-stranded RNA to siRNAs. The resulting deficiency
in tasiRNAs and other RDR6-/DCL4-dependent siRNAs appears to trigger
a feedback mechanism that compensates for the inhibitory effects.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/36/18/5896}
}
@ARTICLE{Shkryl2008,
author = {Shkryl, Yuri N. and Veremeichik, Galina N. and Bulgakov, Victor P.
and Tchernoded, Galina K. and Mischenko, Natalia P. and Fedoreyev,
Sergei A. and Zhuravlev, Yuri N.},
title = {Individual and combined effects of the rolA, B, and C genes on anthraquinone
production in Rubia cordifolia transformed calli},
journal = {Biotechnol. Bioeng.},
year = {2008},
volume = {100},
pages = {118--125},
number = {1},
abstract = {Abstract 10.1002/bit.21727.abs It is known that the rolA, rolB, and
rolC genes of Agrobacterium rhizogenes T-DNA affect processes of
plant development and activate the synthesis of secondary metabolites
in transformed plant cells. Although a synergistic activity of the
rol genes on root formation is well-documented, little is known about
their individual and combined action on secondary metabolism. In
the present investigation, we provide evidence indicating that individual
rolA, rolB, and rolC genes are capable of increasing biosynthesis
of anthraquinones (AQs) in transformed calli of Rubia cordifolia.
The stimulatory effect was due to the increased transcription of
a key gene of AQ biosynthesis, the isochorismate synthase (ICS) gene.
The strongest AQ-stimulating activity was shown for an R. cordifolia
culture expressing rolB at high levels, where rolB ensured a 15-fold
increase of AQ accumulation compared with the control, non-transformed
calli. A tyrosine phosphatase inhibitor abolished the rolB-induced
increase of AQ production, thus indicating the involvement of tyrosine
(de)phosphorylation in the rolB-mediated AQ stimulation. The rolA-
and rolC-expressing cultures produced 2.8- and 4.3-fold higher levels
of AQs, respectively, when compared with the control calli. However,
the effect of rolA, rolB, and rolC on AQ biosynthesis was not synergistic
because rolA and rolC apparently attenuated the stimulatory effect
of rolB on AQ biosynthesis. Therefore, the rol-gene-mediated signals
that promote root formation and those which activate biosynthesis
of secondary metabolites seem to have a point of divergence. Biotechnol.
Bioeng. 2008;100: 118–125. © 2007 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {Agrobacterium rhizogenes, rol genes, isochorismate synthase, anthraquinones,
Rubia cordifolia},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.21727}
}
@ARTICLE{Shkumatava2009,
author = {Shkumatava, Alena and Stark, Alexander and Sive, Hazel and Bartel,
David P.},
title = {Coherent but overlapping expression of microRNAs and their targets
during vertebrate development},
journal = {Genes \& Dev.},
year = {2009},
volume = {23},
pages = {466--481},
number = {4},
month = feb,
abstract = {MicroRNAs (miRNAs) are small noncoding RNAs that direct post-transcriptional
repression of protein-coding genes. In vertebrates, each highly conserved
miRNA typically regulates hundreds of target mRNAs. However, the
precise relationship between expression of the miRNAs and that of
their targets has remained unclear, in part because of the scarcity
of quantitative expression data at cellular resolution. Here we report
quantitative analyses of mRNA levels in miRNA-expressing cells of
the zebrafish embryo, capturing entire miRNA expression domains,
purified to cellular resolution using fluorescent-activated cell
sorting (FACS). Focus was on regulation by miR-206 and miR-133 in
the developing somites and miR-124 in the developing central nervous
system. Comparison of wild-type embryos and those lacking miRNAs
revealed predicted targets that responded to the miRNAs and distinguished
miRNA-mediated mRNA destabilization from other regulatory effects.
For all three miRNAs examined, expression of the miRNAs and that
of their predicted targets usually overlapped. A few targets were
expressed at higher levels in miRNA-expressing cells than in the
rest of the embryo, demonstrating that miRNA-mediated repression
can act in opposition to other regulatory processes. However, for
most targets expression was lower in miRNA-expressing cells than
in the rest of the embryo, indicating that miRNAs usually operate
in concert with the other regulatory machinery of the cell.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/23/4/466}
}
@ARTICLE{Shlien2010,
author = {Shlien, Adam and Baskin, Berivan and Achatz, Maria Isabel W. and
Stavropoulos, Dimitrios J. and Nichols, Kim E. and Hudgins, Louanne
and Morel, Chantal F. and Adam, Margaret P. and Zhukova, Nataliya
and Rotin, Lianne and Novokmet, Ana and Druker, Harriet and Shago,
Mary and Ray, Peter N. and Hainaut, Pierre and Malkin, David},
title = {A Common Molecular Mechanism Underlies Two Phenotypically Distinct
17p13.1 Microdeletion Syndromes},
journal = {The American Journal of Human Genetics},
year = {2010},
volume = {87},
pages = {631--642},
number = {5},
month = nov,
abstract = {DNA copy-number variations (CNVs) underlie many neuropsychiatric conditions,
but they have been less studied in cancer. We report the association
of a 17p13.1 CNV, childhood-onset developmental delay (DD), and cancer.
Through a screen of over 4000 patients with diverse diagnoses, we
identified eight probands harboring microdeletions at TP53 (17p13.1).
We used a purpose-built high-resolution array with 93.75% breakpoint
accuracy to fine map these microdeletions. Four patients were found
to have a common phenotype including DD, hypotonia, and hand and
foot abnormalities, constituting a unique syndrome. Notably, these
patients were not affected with cancer. Moreover, none of the TP53-deletion
patients affected with cancer (n = 4) had neurocognitive impairments.
DD patients have larger deletions, which encompass but do not disrupt
TP53, whereas cancer-affected patients harbor CNVs with at least
one breakpoint within TP53. Most 17p13.1 deletions arise by Alu-mediated
nonallelic homologous recombination. Furthermore, we identify a critical
genomic region associated with DD and containing six underexpressed
genes. We conclude that, although they overlap, 17p13.1 CNVs are
associated with distinct phenotypes depending on the position of
the breakpoint with respect to TP53. Further, detailed characterization
of breakpoints revealed a common formation signature. Future studies
should consider whether other loci in the genome also give rise to
phenotypically distinct disorders by means of a common mechanism,
resulting in a similar formation signature.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S0002929710005239}
}
@ARTICLE{Shockley2009,
author = {Shockley, Keith R. and Lazarenko, Oxana P. and Czernik, Piotr J.
and Rosen, Clifford J. and Churchill, Gary A. and Lecka-Czernik,
Beata},
title = {PPAR?2 nuclear receptor controls multiple regulatory pathways of
osteoblast differentiation from marrow mesenchymal stem cells},
journal = {J. Cell. Biochem.},
year = {2009},
volume = {106},
pages = {232--246},
number = {2},
abstract = {Abstract 10.1002/jcb.21994.abs Rosiglitazone (Rosi), a member of the
thiazolidinedione class of drugs used to treat type 2 diabetes, activates
the adipocyte-specific transcription factor peroxisome proliferator-activated
receptor gamma (PPARγ). This activation causes bone loss in animals
and humans, at least in part due to suppression of osteoblast differentiation
from marrow mesenchymal stem cells (MSC). In order to identify mechanisms
by which PPARγ2 suppresses osteoblastogenesis and promotes adipogenesis
in MSC, we have analyzed the PPARγ2 transcriptome in response to
Rosi. A total of 4,252 transcriptional changes resulted when Rosi
(1 µM) was applied to the U-33 marrow stromal cell line stably transfected
with PPARγ2 (U-33/γ2) as compared to non-induced U-33/γ2 cells.
Differences between U-33/γ2 and U-33 cells stably transfected with
empty vector (U-33/c) comprised 7,928 transcriptional changes, independent
of Rosi. Cell type-, time- and treatment-specific gene clustering
uncovered distinct patterns of PPARγ2 transcriptional control of
MSC lineage commitment. The earliest changes accompanying Rosi activation
of PPARγ2 included effects on Wnt, TGFβ/BMP and G-protein signaling
activities, as well as sustained induction of adipocyte-specific
gene expression and lipid metabolism. While suppression of osteoblast
phenotype is initiated by a diminished expression of osteoblast-specific
signaling pathways, induction of the adipocyte phenotype is initiated
by adipocyte-specific transcriptional regulators. This indicates
that distinct mechanisms govern the repression of osteogenesis and
the stimulation of adipogenesis. The co-expression patterns found
here indicate that PPARγ2 has a dominant role in controlling osteoblast
differentiation and suggests numerous gene-gene interactions that
could lead to the identification of a “master� regulatory scheme
directing this process. J. Cell. Biochem. 106: 232–246, 2009. ©
2008 Wiley-Liss, Inc.},
issn = {1097-4644},
keywords = {PPAR gamma, thiazolidinediones, osteoblast, bone marrow mesenchymal
stem cells, gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.21994}
}
@ARTICLE{Shockley2009a,
author = {Shockley, Keith R. and Witmer, David and Burgess-Herbert, Sarah L.
and Paigen, Beverly and Churchill, Gary A.},
title = {Effects of atherogenic diet on hepatic gene expression across mouse
strains},
journal = {Physiol Genomics},
year = {2009},
volume = {39},
pages = {172--182},
number = {3},
month = nov,
abstract = {Diets high in fat and cholesterol are associated with increased obesity
and metabolic disease in mice and humans. To study the molecular
basis of the metabolic response to dietary fat, 10 inbred strains
of mice were fed atherogenic high-fat and control low-fat diets.
Liver gene expression and whole animal phenotypes were measured and
analyzed in both sexes. The effects of diet, strain, and sex on gene
expression were determined irrespective of complex processes, such
as feedback mechanisms, that could have mediated the genomic responses.
Global gene expression analyses demonstrated that animals of the
same strain and sex have similar transcriptional profiles on a low-fat
diet, but strains may show considerable variability in response to
high-fat diet. Functional profiling indicated that high-fat feeding
induced genes in the immune response, indicating liver damage, and
repressed cholesterol biosynthesis. The physiological significance
of the transcriptional changes was confirmed by a correlation analysis
of transcript levels with whole animal phenotypes. The results found
here were used to confirm a previously identified quantitative trait
locus on chromosome 17 identified in males fed a high-fat diet in
two crosses, PERA x DBA/2 and PERA x I/Ln. The gene expression data
and phenotype data have been made publicly available as an online
tool for exploring the effects of atherogenic diet in inbred mouse
strains (http://cgd-array.jax.org/DietStrainSurvey).},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/39/3/172}
}
@ARTICLE{Shoemaker2010,
author = {Shoemaker, Jason and Gayen, Kalyan and Garcia-Reyero, Natàlia and
Perkins, Edward and Villeneuve, Daniel and Liu, Li and Doyle, Francis},
title = {Fathead minnow steroidogenesis: in silico analyses reveals tradeoffs
between nominal target efficacy and robustness to cross-talk},
journal = {BMC Systems Biology},
year = {2010},
volume = {4},
pages = {89},
number = {1},
abstract = {BACKGROUND:Interpreting proteomic and genomic data is a major challenge
in predictive ecotoxicology that can be addressed by a systems biology
approach. Mathematical modeling provides an organizational platform
to consolidate protein dynamics with possible genomic regulation.
Here, a model of ovarian steroidogenesis in the fathead minnow, Pimephales
promelas, (FHM) is developed to evaluate possible transcriptional
regulation of steroid production observed in microarray studies.RESULTS:The
model was developed from literature sources, integrating key signaling
components (G-protein and PKA activation) with their ensuing effect
on steroid production. The model properly predicted trajectory behavior
of estradiol and testosterone when fish were exposed to fadrozole,
a specific aromatase inhibitor, but failed to predict the steroid
hormone behavior occurring one week post-exposure as well as the
increase in steroid levels when the stressor was removed. In vivo
microarray data implicated three modes of regulation which may account
for over-production of steroids during a depuration phase (when the
stressor is removed): P450 enzyme up-regulation, inhibin down-regulation,
and luteinizing hormone receptor up-regulation. Simulation studies
and sensitivity analysis were used to evaluate each case as possible
source of compensation to endocrine stress.CONCLUSIONS:Simulation
studies of the testosterone and estradiol response to regulation
observed in microarray data supported the hypothesis that the FHM
steroidogenesis network compensated for endocrine stress by modulating
the sensitivity of the ovarian network to global cues coming from
the hypothalamus and pituitary. Model predictions of luteinizing
hormone receptor regulation were consistent with depuration and in
vitro data. These results challenge the traditional approach to network
elucidation in systems biology. Generally, the most sensitive interactions
in a network are targeted for further elucidation but microarray
evidence shows that homeostatic regulation of the steroidogenic network
is likely maintained by a mildly sensitive interaction. We hypothesize
that effective network elucidation must consider both the sensitivity
of the target as well as the target's robustness to biological noise
(in this case, to cross-talk) when identifying possible points of
regulation.},
doi = {10.1186/1752-0509-4-89},
issn = {1752-0509},
pubmedid = {20579396},
url = {http://www.biomedcentral.com/1752-0509/4/89}
}
@ARTICLE{Shoemaker2006,
author = {Shoemaker, John and Saraiva, Margarida and O'Garra, Anne},
title = {GATA-3 Directly Remodels the IL-10 Locus Independently of IL-4 in
CD4+ T Cells},
journal = {J. Immunol.},
year = {2006},
volume = {176},
pages = {3470--3479},
number = {6},
month = mar,
abstract = {IL-10 is a major regulator in inflammatory responses. Although various
transcription factors were defined to enhance IL-10, the molecular
mechanism for the initiation of Il-10 transcription, remains unknown.
mRNA profiling of six distinct primary CD4+ T cell populations showed
differential expression of the transcription factor GATA-3 correlated
with levels of IL-10 expression. We showed that ectopic expression
of GATA-3 in naive primary CD4+ T cells enhanced expression of IL-10
by these cells and uncovered a possible mechanism for this effect.
We found that GATA-3 induced changes of the chromatin structure at
the Il-10 locus and that these changes occur even in the absence
of IL-4. Furthermore we found that in the presence of GATA-3 the
histones at the Il-10 locus become acetylated. Despite being recruited
in vivo to two locations on the Il-10 locus, GATA-3 did not transactivate
the IL-10 promoter. We therefore suggest a key role of GATA-3 in
instructing Il-10 gene expression in primary CD4+ T cells, possibly
by switching and stabilizing the Il-10 locus into a transcriptionally
competent status.},
url = {http://www.jimmunol.org/cgi/content/abstract/176/6/3470}
}
@ARTICLE{Shojaei2008,
author = {Shojaei, Farbod and Menendez, Pablo},
title = {Molecular profiling of candidate human hematopoietic stem cells derived
from human embryonic stem cells},
journal = {Experimental Hematology},
year = {2008},
volume = {36},
pages = {1436--1448},
number = {11},
month = nov,
abstract = {Objective Human embryonic stem cells (hESCs) have been differentiated
into CD45+ hematopoietic cells in vitro. A subset of hESC-derived
CD45+ cells coexpresses CD34 and show progenitor function in colony-forming
units assays. These hESC-derived hematopoietic stem (HSC), or progenitor
cells, display, however, distinct functional properties, including
poor repopulation ability; impaired differentiation; and lack of
homing when compared to HSCs from fetal blood (FB) or cord blood.
Whether these differences are cell-autonomous or driven by their
microenvironment remains to be elucidated.Materials and Methods Here,
to gain insight into the molecular determinants accounting for these
functional differences, a gene-expression profiling comparing candidate
hESC-HSCs vs FB-derived HSCs (FB-HSCs) was conducted.Results Only
2.4% of differentially expressed transcripts were common for FB-HSCs
and candidate hESC-HSCs, suggesting a completely different molecular
signature for HSCs isolated from two different in utero ontogeny
stages. Several key hematopoietic transcription factors, apoptosis
and cycle regulators, and cell aggregation and homing genes may contribute
to explain the functional differences between hESC-HSCs and FB-HSCs.
Importantly, components of Notch and Wnt signaling pathways involved
in HSC self-renewal and hematopoietic specification were significantly
underexpressed in candidate hESC-HSCs.Conclusion Our study provides
a platform to understand the molecular basis underlying hESC-HSCs
functional properties. Future studies are needed to address the functional
role of the transcripts identified here, eventually leading to identification
of intrinsic determinants and cytokines driving physiological specification
of hESCs into definitive HSCs.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4T5V9DS-2/2/91812c83c360b59d103ac22f0d014b59}
}
@ARTICLE{Shorts-Cary2007,
author = {Shorts-Cary, Lynnette and Xu, Mei and Ertel, Jessica and Kleinschmidt-Demasters,
B. K. and Lillehei, Kevin and Matsuoka, Ichiro and Nielsen-Preiss,
Sheila and Wierman, Margaret E.},
title = {Bone Morphogenetic Protein and Retinoic Acid-Inducible Neural Specific
Protein-3 Is Expressed in Gonadotrope Cell Pituitary Adenomas and
Induces Proliferation, Migration, and Invasion},
journal = {Endocrinology},
year = {2007},
volume = {148},
pages = {967--975},
number = {3},
month = mar,
abstract = {Pituitary tumors are common intracranial neoplasms that often result
in endocrine dysfunction due to hormone overproduction or deficiencies
from mass effects. Gonadotrope cell or gonadotropinomas are tumors
that produce LH and/or FSH and represent 40% of macroadenomas. Little
is known about their underlying pathogenic mechanisms. We compared
expression profiles of 10 gonadotropinomas with nine normal pituitaries
by cDNA array and identified bone morphogenetic protein- and retinoic
acid-inducible neural-specific protein-3 (BRINP3) as overexpressed
in tumors, compared with normals. BRINP3 is a novel, normally brain
restricted protein of unknown function. BRINP3 mRNA was expressed
selectively in gonadotropinomas. Subcellular localization studies
showed that BRINP3 was targeted to the mitochondria, but BRINP3 overexpression
was unable to protect pituitary cells against programmed cell death
induced by growth factor withdrawal. However, BRINP3 overexpression
in pituitary gonadotrope cells promoted proliferation, migration,
and invasion. A BRINP3 antibody was raised that demonstrated clustered
expression of BRINP3 protein in gonadotropinomas and not in normal
human pituitary samples. Thus, BRINP3 is a mitochondrially localized
protein that is selectively up-regulated in human gonadotropinomas.
Its actions to increase proliferation, migration, and invasion suggest
it may play an important role in pituitary tumorigenesis.},
url = {http://endo.endojournals.org/cgi/content/abstract/148/3/967}
}
@ARTICLE{Shou2008,
author = {Shou, Jian-Zhong and Hu, Nan and Takikita, Mikiko and Roth, Mark
J. and Johnson, Laura Lee and Giffen, Carol and Wang, Quan-Hong and
Wang, Chaoyu and Wang, Yuan and Su, Hua and Kong, Li-Hui and Emmert-Buck,
Michael R. and Goldstein, Alisa M. and Hewitt, Stephen M. and Taylor,
Philip R.},
title = {Overexpression of CDC25B and LAMC2 mRNA and Protein in Esophageal
Squamous Cell Carcinomas and Premalignant Lesions in Subjects from
a High-Risk Population in China},
journal = {Cancer Epidemiol. Biomarkers Prev.},
year = {2008},
volume = {17},
pages = {1424--1435},
number = {6},
month = jun,
abstract = {Molecular events associated with the initiation and progression of
esophageal squamous cell carcinoma (ESCC) remain poorly understood
but likely hold the key to effective early detection approaches for
this almost invariably fatal cancer. CDC25B and LAMC2 are two promising
early detection candidates emerging from new molecular studies of
ESCC. To further elucidate the role of these two genes in esophageal
carcinogenesis, we did a series of studies to (a) confirm RNA overexpression,
(b) establish the prevalence of protein overexpression, (c) relate
protein overexpression to survival, and (d) explore their potential
as early detection biomarkers. Results of these studies indicated
that CDC25B mRNA was overexpressed ([≥]2-fold overexpression in
tumor compared with normal) in 64% of the 73 ESCC cases evaluated,
whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein
expression was categorized as positive in 59% (144 of 243) of ESCC
cases on a tumor tissue microarray, and nonnegative LAMC2 patterns
of protein expression were observed in 82% (225 of 275) of cases.
Multivariate-adjusted proportional hazard regression models showed
no association between CDC25B protein expression score and risk of
death [hazard ratio (HR) for each unit increase in expression score,
1.00; P = 0.90]; however, several of the LAMC2 protein expression
patterns strongly predicted survival. Using the cytoplasmic pattern
as the reference (the pattern with the lowest mortality), cases with
a diffuse pattern had a 254% increased risk of death (HR, 3.52; P
= 0.007), cases with no LAMC2 expression had a 169% increased risk
of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern
had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein
expression scores in subjects with esophageal biopsies diagnosed
as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased
significantly with morphologic progression. For LAMC2, all normal
and dysplastic patients had a continuous pattern of protein expression,
whereas all ESCCs showed alternative, noncontinuous patterns. This
series of studies showed that both CDC25B and LAMC2 overexpress RNA
and protein in a significant majority of ESCC cases. The strong relation
of LAMC2 pattern of protein expression to survival suggests a role
in prognosis, whereas the association of CDC25B with morphologic
progression indicates a potential role as an early detection marker.
(Cancer Epidemiol Biomarkers Prev 2008;17(6):1424-35)},
url = {http://cebp.aacrjournals.org/cgi/content/abstract/17/6/1424}
}
@ARTICLE{Shou2005,
author = {Shou, Siming and Scott, Virginia and Reed, Cheryl and Hitzemann,
Robert and Stadler, H. Scott},
title = {Transcriptome analysis of the murine forelimb and hindlimb autopod},
journal = {Dev. Dyn.},
year = {2005},
volume = {234},
pages = {74--89},
number = {1},
abstract = {Abstract 10.1002/dvdy.20514.abs To gain insight into the coordination
of gene expression profiles during forelimb and hindlimb differentiation,
a transcriptome analysis of mouse embryonic autopod tissues was performed
using Affymetrix Murine Gene Chips (MOE-430). Forty-four transcripts
with expression differences higher than 2-fold (T test, P ≤0.05)
were detected between forelimb and hindlimb tissues including 38
new transcripts such as Rdh10,Frzb, Tbx18, and Hip that exhibit differential
limb expression. A comparison of gene expression profiles in the
forelimb, hindlimb, and brain revealed 24 limb-signature genes whose
expression was significantly enriched in limb autopod versus brain
tissue (fold change >2, P ≤ 0.05). Interestingly, the genes exhibiting
enrichment in the developing autopod also segregated into significant
fore- and hindlimb-specific clusters (P ≤ 0.05) suggesting that
by E 12.5, unique gene combinations are being used during the differentiation
of each autopod type. Developmental Dynamics 234:74–89, 2005. ©
2005 Wiley-Liss, Inc.},
issn = {1097-0177},
keywords = {distal limb development, gene expression, transcriptome, microarray},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.20514}
}
@ARTICLE{Shoulars2010,
author = {Shoulars, Kevin and Rodriguez, Mary Ann and Thompson, Trellis and
Markaverich, Barry M.},
title = {Regulation of cell cycle and RNA transcription genes identified by
microarray analysis of PC-3 human prostate cancer cells treated with
luteolin},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2010},
volume = {118},
pages = {41--50},
number = {1-2},
month = jan,
abstract = {Prostate cancer is the second leading cause of cancer-related deaths
in men in the United States. Our previous studies have shown that
ligands for the nuclear type II [3H]estradiol binding site such as
luteolin significantly inhibit prostate cancer cells in vitro and
in vivo; however, the role of these ligands in cell growth and proliferation
is poorly understood. In order to further elucidate the molecular
mechanism through which luteolin exerts its effects on PC-3 cells,
cRNA microarray analyses was performed on 38,500 genes to determine
the genes altered by luteolin treatment. The expression of 3331 genes
was changed greater than 1.2-fold after luteolin treatment. Analysis
of the altered genes identified two pathways that were significantly
affected by luteolin. The Cell Cycle Pathway contained 22 down-regulated
genes (including polo-like kinase 1, cyclin A2, cyclin E2 and proliferation
cell nuclear antigen) and one up-regulated gene (cyclin-dependent
kinase inhibitor 1B). In addition, 13 genes were down-regulated by
luteolin in the RNA Transcription Pathway. Real-time polymerase chain
reactions and western blots verified the observations from the microarray.
In addition, two synthetic, chemically distinct type II ligands,
ZN-2 and BMHPC, mimicked the effects of luteolin on gene expression
at the mRNA and protein level in PC-3 cells. Finally, chromatin immunoprecipitation
assays indicated that luteolin exerts its effects on genes by altering
the acetylation state of promoter-associated histones. Taken together,
the data suggest that type II ligands inhibit cell growth and proliferation
through epigenetic control of key genes involved in cell cycle progression
and RNA transcription.},
issn = {0960-0760},
keywords = {Bioflavonoid, Nuclear type II [3H]estradiol binding site, Cell cycle,
RNA transcription},
url = {http://www.sciencedirect.com/science/article/B6T8X-4XG3S8J-1/2/acdfe2f11796571dee5bff76264ae0c3}
}
@ARTICLE{Shoulars2008,
author = {Shoulars, Kevin and Rodriguez, Mary Ann and Thompson, Trellis and
Turk, John and Crowley, Jan and Markaverich, Barry M.},
title = {Regulation of the nitric oxide pathway genes by tetrahydrofurandiols:
Microarray analysis of MCF-7 human breast cancer cells},
journal = {Cancer Letters},
year = {2008},
volume = {264},
pages = {265--273},
number = {2},
month = jun,
abstract = {THF-diols (9,12-oxy-10,13-dihydroxyoctadecanoic and 10,13-oxy-9,12-dihydroxyoctadecanoic
acids) are endocrine disrupters in rats and mitogens in breast cancer
cells. Microarray analyses and real-time PCR analyses on RNA from
THF-treated MCF-7 cells revealed a number of genes (caveolin 1, heat
shock protein 90[alpha] and 90[beta], vascular endothelial growth
factor, ATPase, Ca++ transporting, ubiquitous) in the nitric oxide
pathway (NOP) were targets for THF-diols. Chromatin immunoprecipitation
studies suggest THF-diols modify of histone H4 acetylation at the
caveolin 1 promoter via an epigenetic mechanism. These findings are
consistent with the well-known involvement of NOP genes in cell proliferation
and sexual behavior.},
issn = {0304-3835},
keywords = {Tetrahydrofurandiol, Nitric oxide, Human breast cancer, Growth regulation,
Microarray, Reproduction, Endocrine disruptor},
url = {http://www.sciencedirect.com/science/article/B6T54-4S2VMDT-2/2/7ebe2dd9e2bd8ff41847ee435aa0e20b}
}
@ARTICLE{Shrestha2009,
author = {Shrestha, Pravin Malla and Kube, Michael and Reinhardt, Richard and
Liesack, Werner},
title = {Transcriptional activity of paddy soil bacterial communities},
journal = {Environmental Microbiology},
year = {2009},
volume = {11},
pages = {960--970},
number = {4},
abstract = {Summary Bulk mRNA was used to explore the transcriptional activity
of bacterial communities in oxic versus anoxic paddy soil. Two microbial
cDNA libraries were constructed from composite samples using semi-randomly
primed RT-PCR. cDNAs averaged 500–600 bp in length and were treated
as expressed sequence tags (ESTs). Clustering analysis of 805 random
cDNAs resulted in 179 and 155 different ESTs for the oxic and anoxic
zones respectively. Using an E-value threshold of e−10, a total
of 218 different ESTs could be assigned by blastx, while 116 ESTs
were predicted novel. Both the proportion and significance of the
EST assignments increased with cDNA length. Taxonomic assignment
was more powerful in discriminating between the aerobic and anaerobic
bacterial communities than functional inference, as most ESTs in
both oxygen zones were putative indicators of similar housekeeping
functions, in particular ABC-type transporters. A few ESTs were putative
indicators for community function in a biogeochemical context, such
as β-oxidation of long-chain fatty acids specifically in the oxic
zone. Expressed sequence tags assigned to Alpha- and Betaproteobacteria
were predominantly found in the oxic zone, while those affiliated
with Deltaproteobacteria were more frequently detected in the anoxic
zone. At the genus level, multiple assignments to Bradyrhizobium
and Geobacter were unique to the oxic and anoxic zones respectively.
The phylum-level affiliations of 93 16S rRNA sequences corresponded
well with two taxonomically distinct EST patterns. Expressed sequence
tags affiliated with Acidobacteria and Chloroflexi were frequently
detected in both oxygen zones. In summary, the soil metatranscriptome
is accessible for global analysis and such studies have great potential
in elucidating the taxonomic and functional status of soil bacterial
communities, but study significance depends on the number and length
of cDNAs being randomly analysed.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2008.01821.x}
}
@ARTICLE{Shroyer2005,
author = {Shroyer, Noah F. and Wallis, Deeann and Venken, Koen J.T. and Bellen,
Hugo J. and Zoghbi, Huda Y.},
title = {Gfi1 functions downstream of Math1 to control intestinal secretory
cell subtype allocation and differentiation},
journal = {Genes \& Dev.},
year = {2005},
volume = {19},
pages = {2412--2417},
number = {20},
month = oct,
abstract = {Gfi1 is a transcriptional repressor implicated in lymphomagenesis,
neutropenia, and hematopoietic development, as well as ear and lung
development. Here, we demonstrate that Gfi1 functions downstream
of Math1 in intestinal secretory lineage differentiation. Gfi1-/-
mice lack Paneth cells, have fewer goblet cells, and supernumerary
enteroendocrine cells. Gfi1-/- mice show gene expression changes
consistent with this altered cell allocation. These data suggest
that Gfi1 functions to select goblet/Paneth versus enteroendocrine
progenitors. We propose a model of intestinal cell fate choice in
which {beta}-catenin and Cdx function upstream of Math1, and lineage-specific
genes such as Ngn3 act downstream of Gfi1.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/19/20/2412}
}
@ARTICLE{Shui2008,
author = {Shui, Ying-Bo and Arbeit, Jeffrey M. and Johnson, Randall S. and
Beebe, David C.},
title = {HIF-1: An Age-Dependent Regulator of Lens Cell Proliferation},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {4961--4970},
number = {11},
month = nov,
abstract = {PURPOSE. The lens grows throughout life, and lens size is a major
risk factor for nuclear and cortical cataracts. A previous study
showed that the hypoxic environment around the lens suppressed lens
growth in older rats. The present study was conducted to investigate
the mechanism responsible for the age-dependent decline in lens cell
proliferation. METHODS. Transgenic mice expressing Cre recombinase
in the lens were bred to mice containing floxed Hif1a alleles. Transgenic
mice expressing oxygen insensitive forms of HIF-1{alpha} in lens
epithelial cells were exposed to room air or 60% oxygen. Proliferation
was measured by BrdU labeling and cell death by using the TUNEL assay.
Morphology was assessed in histologic sections. HIF-1{alpha} and
p27KIP1 levels were determined by Western blot. The expression of
HIF-regulated genes was assessed on microarrays. RESULTS. Lenses
lacking Hif1a degenerated, precluding study in older animals. Breathing
60% oxygen reduced HIF-1{alpha} levels and HIF-1-regulated transcripts
in lens epithelial cells from young and older lenses. Overexpression
of oxygen-insensitive HIF-1{alpha} had no effect on lens size, but
suppressed increased proliferation in response to oxygen. Systemic
injection of the iron chelator, 1,10-phenanthroline prevented the
degradation of HIF-1{alpha} and reduced oxygen-induced proliferation.
Increasing oxygen decreased levels of p27KIP1 in the epithelial cells
of older mice, which was prevented by expressing oxygen-insensitive
forms of HIF-1{alpha}. CONCLUSIONS. HIF-1{alpha} is present and HIF-1
is transcriptionally active throughout life, but suppresses growth
only in older lenses. Maintaining elevated levels of p27KIP1 in older
lenses requires HIF-1. p27KIP1 and other growth regulators may selectively
suppress the proliferation of older lens epithelial cells.},
url = {http://www.iovs.org/cgi/content/abstract/49/11/4961}
}
@ARTICLE{Shukla2008,
author = {Shukla, Chitranjan J. and Pennington, Caroline J. and Riddick, Antony
C.P. and Sethia, Krishna K. and Ball, Richard Y. and Edwards, Dylan
R.W.},
title = {Laser-capture microdissection in prostate cancer research: establishment
and validation of a powerful tool for the assessment of tumour–stroma
interactions},
journal = {BJU International},
year = {2008},
volume = {101},
pages = {765--774},
number = {6},
abstract = {OBJECTIVES To describe our experience with the optimization and validation
of laser-capture microdissection (LCM) for biomarker analysis in
prostate tissues. As LCM allows the separation of benign and malignant
epithelial structures and stromal elements, it not only allows identification
of the source of the biomarker, but might also accentuate gene or
protein expression changes by reducing contamination by other cellular
elements. MATERIALS AND METHODS In all, 19 fresh-frozen prostate
tissue samples were subjected to LCM, with the cDNA being analysed
using quantitative polymerase chain reaction for several genes, to
identify the optimum number of cells for capture, as well as gene
markers assessing for the purity of the captured cells. The localization
was further confirmed by in situ hybridization. RESULTS Prostate-specific
antigen (PSA) and cytokeratin 8, were expressed solely by epithelial
cells, whereas hepatocyte growth factor (HGF) and tissue inhibitor
of metalloproteinases-3 (TIMP3) were expressed only by stromal cells,
and the levels of transcripts of these genes were unaltered between
benign and malignant tissues. CONCLUSIONS These data suggest that
PSA, cytokeratin 8, HGF and TIMP3 are reliable gene markers of purity
of epithelial and stromal compartments for LCM of prostate tumours.
Although this technique is not new and is increasingly used in laboratories,
it needs optimization and stringent validation criteria before data
analysis. This applies to all tissue types subjected to LCM.},
issn = {1464-410X},
keywords = {prostate, laser-capture microdissection, validation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-410X.2007.07372.x}
}
@ARTICLE{Shum2011,
author = {Shum, Winnie Waichi and Da Silva, Nicolas and Belleannee, Clemence
and McKee, Mary and Brown, Dennis and Breton, Sylvie},
title = {Regulation of V-ATPase recycling via a RhoA- and ROCKII-dependent
pathway in epididymal clear cells},
journal = {Am J Physiol Cell Physiol},
year = {2011},
volume = {301},
pages = {C31-43},
number = {1},
abstract = {Luminal acidification in the epididymis is critical for sperm maturation
and storage. Clear cells express the vacuolar H+-ATPase (V-ATPase)
in their apical membrane and are major contributors to proton secretion.
We showed that this process is regulated via recycling of V-ATPase-containing
vesicles. We now report that RhoA and its effector ROCKII are enriched
in rat epididymal clear cells. In addition, cortical F-actin was
detected beneath the apical membrane and along the lateral membrane
of "resting" clear cells using a pan-actin antibody or phalloidin-TRITC.
In vivo luminal perfusion of the cauda epididymal tubule with the
ROCK inhibitors Y27632 (10-30 {micro}M) and HA1077 (30 {micro}M)
or with the cell-permeable Rho inhibitor Clostridium botulinum C3
transferase (3.75 {micro}g/ml) induced the apical membrane accumulation
of V-ATPase and extension of V-ATPase-labeled microvilli in clear
cells. However, these newly formed microvilli were devoid of ROCKII.
In addition, Y27632 (30 {micro}M) or HA1077 (30 {micro}M) decreased
the ratio of F-actin to G-actin detected by Western blot analysis
in epididymal epithelial cells, and Y27632 also decreased the ratio
of F-actin to G-actin in clear cells isolated by fluorescence activated
cell sorting from B1-enhanced green fluorescence protein (EGFP) transgenic
mice. These results provide evidence that depolymerization of the
cortical actin cytoskeleton via inhibition of RhoA or its effector
ROCKII favors the recruitment of V-ATPase from the cytosolic compartment
into the apical membrane in clear cells. In addition, our data suggest
that the RhoA-ROCKII pathway is not locally involved in the elongation
of apical microvilli. We propose that inhibition of RhoA-ROCKII might
be part of the intracellular signaling cascade that is triggered
upon agonist-induced apical membrane V-ATPase accumulation.},
doi = {10.1152/ajpcell.00198.2010},
eprint = {http://ajpcell.physiology.org/cgi/reprint/301/1/C31.pdf},
url = {http://ajpcell.physiology.org/cgi/content/abstract/301/1/C31}
}
@ARTICLE{Shureiqi2010,
author = {Shureiqi, Imad and Chen, Dongning and Day, R. Sue and Zuo, Xiangsheng
and Hochman, Fredric Lyone and Ross, William A. and Cole, Rhonda
A. and Moy, Ofie and Morris, Jeffrey S. and Xiao, Lianchun and Newman,
Robert A. and Yang, Peiying and Lippman, Scott M.},
title = {Profiling Lipoxygenase Metabolism in Specific Steps of Colorectal
Tumorigenesis},
journal = {Cancer Prevention Research},
year = {2010},
volume = {3},
pages = {829--838},
number = {7},
month = jul,
abstract = {Lipoxygenases (LOX) are key enzymes for the oxidative metabolism of
polyunsaturated fatty acids into biologically active products. Clinical
data on comparative levels of various LOX products in tumorigenesis
are lacking. Therefore, we examined the profiles of several LOX products
(5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2) by liquid chromatography/tandem
mass spectrometry in the major steps of colorectal tumorigenesis
(normal, polyp, and cancer) in a clinical study of 125 subjects (49
with normal colon, 36 with colorectal polyps, and 40 with colorectal
cancer) who underwent prospective colorectal biopsies to control
for various potential confounding factors (e.g., diet, medications).
Mean 13-hydroxyoctadecadienoic acid (13-HODE) levels were significantly
higher in normal colon [mean, 36.11 ng/mg protein; 95% confidence
interval (95% CI), 31.56-40.67] than in paired colorectal cancer
mucosa (mean, 27.01 ng/mg protein; 95% CI, 22.00-32.02; P = 0.0002),
and in normal colon (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.34)
than in paired colorectal polyp mucosa (mean, 28.07 ng/mg protein;
95% CI, 23.66-32.48; P < 0.001). Mean 13-HODE levels, however, were
similar between the left (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.35)
and the right normal colon (mean, 32.46 ng/mg protein; 95% CI, 27.95-36.98;
P = 0.09). No significant differences with regard to 12- or 15-hydroxyeicosatetraenoic
acid or leukotriene B4 levels were detected between normal, polyp,
and cancer mucosae. 15-LOX-1 inhibited interleukin-1{beta} expression.
This study establishes that reduced 13-HODE levels are a specific
alteration in the LOX product profile associated with human colorectal
tumorigenesis. Cancer Prev Res; 3(7); 829-38. (C)2010 AACR.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/3/7/829}
}
@ARTICLE{Shureiqi2005,
author = {Shureiqi, Imad and Wu, Yuanqing and Chen, Dongning and Yang, Xiu
L. and Guan, Baoxiang and Morris, Jeffrey S. and Yang, Peiying and
Newman, Robert A. and Broaddus, Russell and Hamilton, Stanley R.
and Lynch, Patrick and Levin, Bernard and Fischer, Susan M. and Lippman,
Scott M.},
title = {The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell
Terminal Differentiation and Tumorigenesis},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {11486--11492},
number = {24},
month = dec,
abstract = {Terminal differentiation is an important event for maintaining normal
homeostasis in the colorectal epithelium, and the loss of apoptosis
is an important mechanism underlying colorectal tumorigenesis. The
very limited current data on the role of lipoxygenase (LOX) metabolism
in tumorigenesis suggests that the oxidative metabolism of linoleic
and arachidonic acid possibly shifts from producing antitumorigenic
15-LOX-1 and 15-LOX-2 products to producing protumorigenic 5-LOX
and 12-LOX products. We examined whether this shift occurs in vitro
in the human colon cancer cell line Caco-2 in association with the
loss of terminal differentiation and apoptosis, or in vivo during
the formation of colorectal adenomas in patients with familial adenomatous
polyposis (FAP). Restoring terminal differentiation and apoptosis
of Caco-2 cells increased the mRNA levels of 5-LOX, 15-LOX-2, and
15-LOX-1, but the only significant increases in protein expression
and enzymatic activity were of 15-LOX-1. In FAP patients, 15-LOX-1
expression and activity were significantly down-regulated in adenomas
(compared with paired nonneoplastic epithelial mucosa), whereas 5-LOX
and 15-LOX-2 protein expressions and enzymatic activities were not.
We conducted a validation study with immunohistochemical testing
in a second group of FAP patients; 15-LOX-1 expression was down-regulated
in colorectal adenomas (compared with nonneoplastic epithelial mucosa)
in 87% (13 of 15) of this group. We confirmed the mechanistic relevance
of these findings by demonstrating that ectopically restoring 15-LOX-1
expression reestablished apoptosis in Caco-2 cells. Therefore, 15-LOX-1
down-regulation rather than a shift in the balance of LOXs is likely
the dominant alteration in LOX metabolism which contributes to colorectal
tumorigenesis by repressing apoptosis. (Cancer Res 2005; 65(24):
11486-92)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/24/11486}
}
@ARTICLE{Shutt2005,
author = {Shutt, Cheryl K. and Pounder, June I. and Page, Sam R. and Schaecher,
Barbara J. and Woods, Gail L.},
title = {Clinical Evaluation of the DiversiLab Microbial Typing System Using
Repetitive-Sequence-Based PCR for Characterization of Staphylococcus
aureus Strains},
journal = {J. Clin. Microbiol.},
year = {2005},
volume = {43},
pages = {1187--1192},
number = {3},
month = mar,
abstract = {The DiversiLab System, which includes microfluidics-based detection,
reagent kits, and software for data processing and analysis, is an
automated method using repetitive sequence-based PCR (rep-PCR) for
microbial strain typing. To assess the reliability of the DiversiLab
System for strain characterization of Staphylococcus aureus, we tested
clinical isolates sent to ARUP Laboratories for typing and compared
results to those of pulsed field electrophoresis (PFGE) aided by
the cluster analysis provided by BioNumerics software. spa typing
was performed when the results of these two methods for an outbreak
were not concordant. The study included 89 S. aureus isolates (65
mecA positive, 24 mecA negative) from 19 outbreaks (2 to 11 isolates/outbreak).
The DiversiLab and PFGE-BioNumerics results were concordant for 15
of the 19 outbreaks. For the remaining four outbreaks, there was
partial concordance between the two methods. spa typing results were
the same as or more similar to rep-PCR results for three of those
outbreaks and were more similar to PFGE results for one. With regard
to performance, the DiversiLab system was considerably less labor
intensive than PFGE and provided results in less than 24 h, compared
with 2 to 3 days for PFGE. Additionally, the Web-based DiversiLab
software provides standardized comparisons among isolates almost
instantaneously and generates user-friendly, customized reports.},
url = {http://jcm.asm.org/cgi/content/abstract/43/3/1187}
}
@ARTICLE{Siahpoosh2012,
author = {Mohammad R. Siahpoosh and Diego H. Sanchez and Armin Schlereth and
Graham N. Scofield and Robert T. Furbank and Joost T. van Dongen
and Joachim Kopka},
title = {Modification of OsSUT1 gene expression modulates the salt response
of rice Oryza sativa cv. Taipei 309},
journal = {Plant Science},
year = {2012},
volume = {182},
pages = {101 - 111},
number = {0},
note = {Abiotic stress tolerances},
abstract = {A metabolic depletion syndrome was discovered at early vegetative
stages in roots of salt sensitive rice cultivars after prolonged
exposure to 100 mM NaCl. Metabolite profiling analyses demonstrate
that this syndrome is part of the terminal stages of the rice salt
response. The phenotype encompasses depletion of at least 30 primary
metabolites including sucrose, glucose, fructose, glucose-6-P, fructose-6P,
organic- and amino-acids. Based on these observations we reason that
sucrose allocation to the root may modify the rice response to high
salt. This hypothesis was tested using antisense lines of the salt
responsive OsSUT1 gene in the salt sensitive Taipei 309 cultivar.
Contrary to our expectations of a plant system impaired in one component
of sucrose transport, we find improved gas exchange and photosynthetic
performance as well as maintenance of sucrose levels in the root
under high salinity. Two independent OsSUT1 lines with an antisense
inhibition similar to the naturally occurring salt induced reduction
of OsSUT1 gene expression showed these phenomena but not a more extreme
antisense inhibition line. We investigated the metabolic depletion
syndrome by metabolomic and physiological approaches and discuss
our results with regard to the potential role of sucrose transporters
and sucrose transport for rice salt acclimation.},
doi = {10.1016/j.plantsci.2011.01.001},
issn = {0168-9452},
keywords = {Oryza sativa},
url = {http://www.sciencedirect.com/science/article/pii/S0168945211000185}
}
@ARTICLE{Siatskas2005,
author = {Siatskas, Christopher and Underwood, John and Ramezani, Ali and Hawley,
Robert G. and Medin, Jeffrey A.},
title = {Specific pharmacological dimerization of KDR in lentivirally transduced
human hematopoietic cells activates antiapoptotic and proliferative
mechanisms},
journal = {FASEB J},
year = {2005},
volume = {19},
pages = {1752-1754},
month = aug,
abstract = {Selective and regulatable expansion of transduced cells could augment
gene therapy for many disorders. The activation of modified growth
factor receptors via synthetic chemical inducers of dimerization
allows for the coordinated growth of transduced cells. This system
can also provide information on specific receptor-mediated signaling
without interference from other family members. Although several
receptor subunits have been investigated in this context, little
is known about the precise molecular events associated with dimerizer-initiated
signaling. We have constructed and expressed an AP20187-regulated
KDR chimeric receptor in human TF1 cells and analyzed activation
of this gene switch using functional, biochemical, and microarray
analyses. When deprived of natural ligands, GM-CSF, interleukin-3,
or erythropoietin, AP20187 prevented apoptosis of transduced TF1
cells, induced dose-dependent proliferation, and supported long-term
growth. In addition, AP20187 stimulation activated the signaling
molecules associated with mitogen-activated protein kinase and phosphatidyl-inositol
3-kinase/Akt pathways. Microarray analysis determined that a number
of transcripts involved in a variety of cellular processes were differentially
expressed. Notably, mRNAs affiliated with heat stress, including
Hsp70 and Hsp105, were up-regulated. Functional assays showed that
Hsp70 and Hsp105 protected transduced TF1 cells from apoptosis and
premature senescence, in part through regulation of Akt. These observations
delineate specific roles for kinase insert domain-containing receptor,
or KDR, signaling and suggest strategies to endow genetically modified
cells with a survival advantage enabling the generation of adequate
cell numbers for therapeutic outcomes. Key words: heat shock proteins
selective growth advantage gene therapy microarray analysis AP20187},
url = {http://www.fasebj.org/cgi/content/abstract/05-4006fjev1}
}
@ARTICLE{Siboo2008,
author = {Siboo, Ian R. and Chaffin, Donald O. and Rubens, Craig E. and Sullam,
Paul M.},
title = {Characterization of the Accessory Sec System of Staphylococcus aureus},
journal = {J. Bacteriol.},
year = {2008},
volume = {190},
pages = {6188--6196},
number = {18},
month = sep,
abstract = {The SraP adhesin of Staphylococcus aureus is a member of a highly
conserved family of serine-rich surface glycoproteins of gram-positive
bacteria. For streptococci, export of the SraP homologs requires
a specialized transport pathway (the accessory Sec system). Compared
to streptococci, however, SraP is predicted to differ in its signal
peptide and glycosylation, which may affect its dependence on a specialized
system for transport. In addition, two genes (asp4 and asp5) essential
for export in Streptococcus gordonii are missing in S. aureus. Thus,
the selectivity of the accessory Sec system in S. aureus may also
differ compared to streptococci. To address these issues, the five
genes encoding the putative accessory Sec system (secY2, secA2, and
asp1-3) were disrupted individually in S. aureus ISP479C, and the
resultant mutants were examined for SraP export. Disruption of secA2
resulted in the near complete loss of SraP surface expression. Similar
results were seen with disruption of secY2 and asp1, asp2, or asp3.
To assess whether the accessory Sec system transported other substrates,
we compared secreted proteomes of ISP479C and a secA2 isogenic mutant,
by two-dimensional fluorescence difference gel electrophoresis. Although
two consistent differences in proteome content were noted between
the strains, neither protein appeared to be a likely substrate for
accessory Sec export. Thus, the accessory Sec system of S. aureus
is required for the export of SraP, and it appears to be dedicated
to the transport of this substrate exclusively.},
url = {http://jb.asm.org/cgi/content/abstract/190/18/6188}
}
@ARTICLE{Sibug2007,
author = {Sibug, R.M. and Datson, N. and Tijssen, A.M.I. and Morsink, M. and
de Koning, J. and de Kloet, E.R. and Helmerhorst, F.M.},
title = {Effects of urinary and recombinant gonadotrophins on gene expression
profiles during the murine peri-implantation period},
journal = {Hum. Reprod.},
year = {2007},
volume = {22},
pages = {75--82},
number = {1},
month = jan,
abstract = {BACKGROUND: Controlled ovarian stimulation (COS) with urinary gonadotrophins
but not recombinant gonadotrophins, adversely affect the implantation
process. In this study, we investigated the effects of urinary and
recombinant gonadotrophins on gene expression profiles at implantation
sites during the mouse peri-implantation period and the possible
molecular mechanisms involved in the detrimental effects of urinary
gonadotrophins using microarray technology. METHODS: Adult female
CD1 mice were treated with (i) urinary human FSH (hFSH) and urinary
HCG, (ii) recombinant hFSH and recombinant human LH or (iii) saline.
Gene expression profiling with GeneChip mouse genome 430 2.0 arrays,
containing 45 101 probe sets, was performed using implantation sites
on embryonic day 5. Data were statistically analysed using Significance
Analysis of Microarrays. Ten genes from the microarray analysis were
selected for validation using quantitative RT-PCR (qRT-PCR). A parallel
group of pregnant mice was allowed to give birth to study the effect
of gonadotrophins on resorption. RESULTS: Urinary gonadotrophins
differentially up-regulated the expression of 30 genes, increased
resorption and reduced litter size, whereas recombinant gonadotrophins
did not. Nine of the 10 genes were confirmed by qRT-PCR. CONCLUSIONS:
Urinary gonadotrophins, but not recombinant gonadotrophins, exerted
differential effects on gene expression during the murine peri-implantation
period. These findings might contribute to improve protocols for
COS, leading to higher successful pregnancy rates.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/22/1/75}
}
@ARTICLE{Sibut2011,
author = {Sibut, Vonick and Hennequet-Antier, Christelle and Le Bihan-Duval,
Elisabeth and Marthey, Sylvain and Duclos, Michel and Berri, Cécile},
title = {Identification of differentially expressed genes in chickens differing
in muscle glycogen content and meat quality},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {112},
number = {1},
abstract = {BACKGROUND:The processing ability of poultry meat is highly related
to its ultimate pH, the latter being mainly determined by the amount
of glycogen in the muscle at death. The genetic determinism of glycogen
and related meat quality traits has been established in the chicken
but the molecular mechanisms involved in variations in these traits
remain to be fully described. In this study, Chicken Genome Arrays
(20 K) were used to compare muscle gene expression profiles of chickens
from Fat (F) and Lean (L) lines that exhibited high and low muscle
glycogen content, respectively, and of individuals exhibiting extremely
high (G+) or low (G-) muscle glycogen content originating from the
F2 cross between the Fat and Lean lines. Real-time RT-PCR was subsequently
performed to validate the differential expression of genes either
selected from the microarray analysis or whose function in regulating
glycogen metabolism was well known.RESULTS:Among the genes found
to be expressed in chicken P. major muscle, 197 and 254 transcripts
appeared to be differentially expressed on microarrays for the F
vs. L and the G+ vs. G- comparisons, respectively. Some involved
particularly in lipid and carbohydrate metabolism were selected for
further validation studies by real-time RT-PCR. We confirmed that,
as in mammals, the down-regulation of CEBPB and RGS2 coincides with
a decrease in peripheral adiposity in the chicken, but these genes
are also suggested to affect muscle glycogen turnover through their
role in the cAMP-dependent signalling pathway. Several other genes
were suggested to have roles in the regulation of glycogen storage
in chicken muscle. PDK4 may act as a glycogen sensor in muscle, UGDH
may compete for glycogen synthesis by using UDP-glucose for glucoronidation,
and PRKAB1, PRKAG2, and PHKD may impact on glycogen turnover in muscle,
through AMP-activated signalling pathways.CONCLUSIONS:This study
is the first stage in the understanding of molecular mechanisms underlying
variations in poultry meat quality. Large scale analyses are now
required to validate the role of the genes identified and ultimately
to find molecular markers that can be used for selection or to optimize
rearing practices.},
doi = {10.1186/1471-2164-12-112},
issn = {1471-2164},
pubmedid = {21324179},
url = {http://www.biomedcentral.com/1471-2164/12/112}
}
@ARTICLE{Siciliano2007,
author = {Siciliano, Valeria and Genre, Andrea and Balestrini, Raffaella and
Cappellazzo, Gilda and deWit, Pierre J.G.M. and Bonfante, Paola},
title = {Transcriptome Analysis of Arbuscular Mycorrhizal Roots during Development
of the Prepenetration Apparatus},
journal = {Plant Physiology},
year = {2007},
volume = {144},
pages = {1455--1466},
number = {3},
month = jul,
abstract = {Information on changes in the plant transcriptome during early interaction
with arbuscular mycorrhizal (AM) fungi is still limited since infections
are usually not synchronized and plant markers for early stages of
colonization are not yet available. A prepenetration apparatus (PPA),
organized in epidermal cells during appressorium development, has
been reported to be responsible for assembling a trans-cellular tunnel
to accommodate the invading fungus. Here, we used PPAs as markers
for cell responsiveness to fungal contact to investigate gene expression
at this early stage of infection with minimal transcript dilution.
PPAs were identified by confocal microscopy in transformed roots
of Medicago truncatula expressing green fluorescent protein-HDEL,
colonized by the AM fungus Gigaspora margarita. A PPA-targeted suppressive-subtractive
cDNA library was built, the cDNAs were cloned and sequenced, and,
consequently, 107 putative interaction-specific genes were identified.
The expression of a subset of 15 genes, selected by reverse northern
dot blot screening, and five additional genes, potentially involved
in PPA formation, was analyzed by real-time reverse transcription-polymerase
chain reaction and compared with an infection stage, 48 h after the
onset of the PPA. Comparison of the expression profile of G. margarita-inoculated
wild type and the mycorrhiza-defective dmi3-1 mutant of M. truncatula
revealed that an expansin-like gene, expressed in wild-type epidermis
during PPA development, can be regarded as an early host marker for
successful mycorrhization. A putative Avr9/Cf-9 rapidly elicited
gene, found to be up-regulated in the mutant, suggests novel regulatory
roles for the DMI3 protein in the early mycorrhization process.},
url = {http://www.plantphysiol.org/cgi/content/abstract/144/3/1455}
}
@ARTICLE{Siddens2008,
author = {Siddens, Lisbeth K. and Henderson, Marilyn C. and VanDyke, Jonathan
E. and Williams, David E. and Krueger, Sharon K.},
title = {Characterization of mouse flavin-containing monooxygenase transcript
levels in lung and liver, and activity of expressed isoforms},
journal = {Biochemical Pharmacology},
year = {2008},
volume = {75},
pages = {570--579},
number = {2},
month = jan,
abstract = {The significance of active versus inactive flavin-containing monooxygenase
2 (FMO2) for human drug and xenobiotic metabolism and sensitivity
is unknown, but the underlying ethnic polymorphism is well documented.
We used quantitative real-time PCR to measure message levels of Fmo1,
Fmo2, Fmo3 and Fmo5 in lung and liver from eight strains of 8 week
old female mice to determine if a strain could be identified that
predominately expressed Fmo2 in lung, recapitulating the human FMO
expression profile and being the ideal strain for Fmo2 knockout studies.
We also characterized enzyme activity of baculovirus expressed mouse
Fmo1, Fmo2 and Fmo3 to identify a substrate or incubation conditions
capable of discriminating Fmo2 from Fmo mixtures. Fmo transcript
expression patterns were similar for all strains. In lung, 59% of
total FMO message was Fmo2, but Fmo1 levels were also high, averaging
34%, whereas Fmo3 and Fmo5 levels were 2 and 5%, respectively. In
liver, Fmo1, Fmo2, Fmo3 and Fmo5 contributed 16, 1, 7 and 76% respectively,
of detected message. Peak activity varied by isoform and was pH-
and substrate-dependent. Fmo3 oxidation of methyl p-tolyl sulfide
was negligible at pH 9.5, but Fmo3 oxidation of methimazole was comparable
to Fmo1 and Fmo2. Heating microsomes at 50 °C for 10 min eliminated
most Fmo1 and Fmo3 activity, while 94% of Fmo2 activity remained.
Measurement of activity in heated and unheated lung and liver microsomes
verified relative transcript abundance. Our results show that dual
Fmo1/2 knockouts will be required to model the human lung FMO profile.},
issn = {0006-2952},
keywords = {Quantitative real-time PCR, In vitro expression, Flavin-containing
monooxygenase, Mouse, Pulmonary expression, Hepatic expression},
url = {http://www.sciencedirect.com/science/article/B6T4P-4PMJJYG-6/2/ede31bb1ca0cf122532bd731fb932a2c}
}
@ARTICLE{Siddique2009,
author = {Siddique, Shahid and Endres, Stefanie and Atkins, Jamie M. and Szakasits,
Dagmar and Wieczorek, Krzysztof and Hofmann, Julia and Blaukopf,
Claudia and Urwin, Peter E. and Tenhaken, Raimund and Grundler, Florian
M. W. and Kreil, David P. and Bohlmann, Holger},
title = {Myo-inositol oxygenase genes are involved in the development of syncytia
induced by Heterodera schachtii in Arabidopsis roots},
journal = {New Phytologist},
year = {2009},
volume = {184},
pages = {457--472},
number = {2},
abstract = {Summary * • In plants, UDP-glucuronic acid is synthesized by the
oxidation of UDP-glucose by UDP-glucose dehydrogenase or the oxygenation
of free myo-inositol by myo-inositol oxygenase (MIOX). In Arabidopsis,
myo-inositol oxygenase is encoded by four genes. Transcriptome analysis
of syncytia induced by the cyst nematode Heterodera schachtii in
Arabidopsis roots revealed that MIOX genes are among the most strongly
upregulated genes. * • We have used β-glucuronidase (GUS) analysis,
in situ reverse transcription polymerase chain reaction (RT-PCR),
and real-time RT-PCR to study the expression of all four MIOX genes
in syncytia induced by H. schachtii in Arabidopsis roots. All these
methods showed that MIOX genes are strongly induced in syncytia.
GeneChip data were analysed for the expression of genes related to
the MIOX pathway (mapman). * • Two complementary double mutants
were used to study the importance of MIOX genes. Results of the infection
assay with double mutants in two combinations (Δmiox1+2, Δmiox4+5)
showed a significant reduction (PÂ <Â 0.05) in the number of females
per plant when compared with the wild-type. Furthermore, syncytia
in double mutants were significantly smaller than in wild-type plants.
* • Our data demonstrate an important role of the MIOX genes
for syncytium development and for the development of female nematodes.},
issn = {1469-8137},
keywords = {Arabidopsis, Heterodera schachtii, mapman, myo-inositol oxygenase,
syncytium, roots},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2009.02981.x}
}
@ARTICLE{Siddiqui2011,
author = {Siddiqui, Huma and Nederbragt, Alexander and Lagesen, Karin and Jeansson,
Stig and Jakobsen, Kjetill},
title = {Assessing diversity of the female urine microbiota by high throughput
sequencing of 16S rDNA amplicons},
journal = {BMC Microbiology},
year = {2011},
volume = {11},
pages = {244},
number = {1},
abstract = {BACKGROUND:Urine within the urinary tract is commonly regarded as
"sterile" in cultivation terms. Here, we present a comprehensive
in-depth study of bacterial 16S rDNA sequences associated with urine
from healthy females by means of culture-independent high-throughput
sequencing techniques.RESULTS:Sequencing of the V1V2 and V6 regions
of the 16S ribosomal RNA gene using the 454 GS FLX system was performed
to characterize the possible bacterial composition in 8 culture-negative
(<100,000 CFU/ml) healthy female urine specimens. Sequences were
compared to 16S rRNA databases and showed significant diversity,
with the predominant genera detected being Lactobacillus, Prevotella
and Gardnerella. The bacterial profiles in the female urine samples
studied were complex; considerable variation between individuals
was observed and a common microbial signature was not evident. Notably,
a significant amount of sequences belonging to bacteria with a known
pathogenic potential was observed. The number of operational taxonomic
units (OTUs) for individual samples varied substantially and was
in the range of 20 - 500.CONCLUSIONS:Normal female urine displays
a noticeable and variable bacterial 16S rDNA sequence richness, which
includes fastidious and anaerobic bacteria previously shown to be
associated with female urogenital pathology.},
doi = {10.1186/1471-2180-11-244},
issn = {1471-2180},
pubmedid = {22047020},
url = {http://www.biomedcentral.com/1471-2180/11/244}
}
@ARTICLE{Sideri2009,
author = {Sideri, Theodora C. and Willetts, Sylvia A. and Avery, Simon V.},
title = {Methionine sulphoxide reductases protect iron-sulphur clusters from
oxidative inactivation in yeast},
journal = {Microbiology},
year = {2009},
volume = {155},
pages = {612--623},
number = {2},
month = feb,
abstract = {Methionine residues and iron-sulphur (FeS) clusters are primary targets
of reactive oxygen species in the proteins of micro-organisms. Here,
we show that methionine redox modifications help to preserve essential
FeS cluster activities in yeast. Mutants defective for the highly
conserved methionine sulphoxide reductases (MSRs; which re-reduce
oxidized methionines) are sensitive to many pro-oxidants, but here
exhibited an unexpected copper resistance. This phenotype was mimicked
by methionine sulphoxide supplementation. Microarray analyses highlighted
several Cu and Fe homeostasis genes that were upregulated in the
mxr{Delta} double mutant, which lacks both of the yeast MSRs. Of
the upregulated genes, the Cu-binding Fe transporter Fet3p proved
to be required for the Cu-resistance phenotype. FET3 is known to
be regulated by the Aft1 transcription factor, which responds to
low mitochondrial FeS-cluster status. Here, constitutive Aft1p expression
in the wild-type reproduced the Cu-resistance phenotype, and FeS-cluster
functions were found to be defective in the mxr{Delta} mutant. Genetic
perturbation of FeS activity also mimicked FET3-dependent Cu resistance.
55Fe-labelling studies showed that FeS clusters are turned over more
rapidly in the mxr{Delta} mutant than the wild-type, consistent with
elevated oxidative targeting of the clusters in MSR-deficient cells.
The potential underlying molecular mechanisms of this targeting are
discussed. Moreover, the results indicate an important new role for
cellular MSR enzymes in helping to protect the essential function
of FeS clusters in aerobic settings.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/155/2/612}
}
@ARTICLE{Sideridou2011,
author = {Sideridou, Maria and Zakopoulou, Roubini and Evangelou, Konstantinos
and Liontos, Michalis and Kotsinas, Athanassios and Rampakakis, Emmanouil
and Gagos, Sarantis and Kahata, Kaoru and Grabusic, Kristina and
Gkouskou, Kalliopi and Trougakos, Ioannis P. and Kolettas, Evangelos
and Georgakilas, Alexandros G. and Volarevic, Sinisa and Eliopoulos,
Aristides G. and Zannis-Hadjopoulos, Maria and Moustakas, Aristidis
and Gorgoulis, Vassilis G.},
title = {Cdc6 expression represses E-cadherin transcription and activates
adjacent replication origins},
journal = {J. Cell Biol.},
year = {2011},
volume = {195},
pages = {1123-1140},
number = {7},
abstract = {E-cadherin (CDH1) loss occurs frequently in carcinogenesis, contributing
to invasion and metastasis. We observed that mouse and human epithelial
cell lines overexpressing the replication licensing factor Cdc6 underwent
phenotypic changes with mesenchymal features and loss of E-cadherin.
Analysis in various types of human cancer revealed a strong correlation
between increased Cdc6 expression and reduced E-cadherin levels.
Prompted by these findings, we discovered that Cdc6 repressed CDH1
transcription by binding to the E-boxes of its promoter, leading
to dissociation of the chromosomal insulator CTCF, displacement of
the histone variant H2A.Z, and promoter heterochromatinization. Mutational
analysis identified the Walker B motif and C-terminal region of Cdc6
as essential for CDH1 transcriptional suppression. Strikingly, CTCF
displacement resulted in activation of adjacent origins of replication.
These data demonstrate that Cdc6 acts as a molecular switch at the
E-cadherin locus, linking transcriptional repression to activation
of replication, and provide a telling example of how replication
licensing factors could usurp alternative programs to fulfill distinct
cellular functions.},
doi = {10.1083/jcb.201108121},
eprint = {http://jcb.rupress.org/cgi/reprint/195/7/1123.pdf},
url = {http://jcb.rupress.org/cgi/content/abstract/195/7/1123}
}
@ARTICLE{Sieben2005,
author = {Sieben, Nathalie L.G. and Oosting, Jan and Flanagan, Adrienne M.
and Prat, Jaime and Roemen, Guido M.J.M. and Kolkman-Uljee, Sandra
M. and van Eijk, Ronald and Cornelisse, Cees J. and Fleuren, Gert
Jan and van Engeland, Manon},
title = {Differential Gene Expression in Ovarian Tumors Reveals Dusp 4 and
Serpina 5 As Key Regulators for Benign Behavior of Serous Borderline
Tumors},
journal = {J. Clin. Oncol.},
year = {2005},
volume = {23},
pages = {7257--7264},
number = {29},
month = oct,
abstract = {PURPOSE: Ovarian serous borderline tumors (SBT) are characterized
by arborizing papillae lined by stratified epithelial cells, varying
atypia, and absence of stromal invasion. Originally, these tumors
have been classified as borderline because they behaved in a remarkably
indolent manner, even with widespread tumor deposits called implants
and the presence of lymph node involvement. The molecular biology
of these lesions has just begun to be explored. High prevalence of
B-RAF/K-RAS mutations in SBTs in contrast to serous carcinomas (SCAs)
indicates that the mitogenic RAS-RAF-MEK-ERK-MAP kinase pathway is
crucial for the pathogenesis of SBTs. The purpose of this study was
to further unravel the genetic pathways through which SBTs develop,
with a special focus on explaining the generally benign SBT behavior.
MATERIALS AND METHODS: We generated RNA expression profiles of 38
ovarian serous neoplasms. Global Test pathway analysis and significance
analysis of microarrays (SAM) of the expression profiles was performed.
RESULTS: SAM and Global Testing showed that although the mitogenic
pathway is activated in SBTs, activation of downstream genes involved
in extracellular matrix (ECM) degradation is absent, suggesting an
uncoupling of both events. In addition, we show that two genes involved
in regulating this uncoupling, ERK-inhibitor Dusp 4 and uPA-inhibitor
Serpina 5, are downregulated in SCAs in contrast to SBTs. In SCAs,
this was associated with downstream MMP-9 activation at both mRNA
and protein level. CONCLUSION: We propose that the putative tumor
suppressor genes Dusp 4 and Serpina 5 provide a major clue to the
indolent behavior of SBTs.},
url = {http://jco.ascopubs.org/cgi/content/abstract/23/29/7257}
}
@ARTICLE{Sieben2005a,
author = {Sieben, Vincent J. and Backhouse, Christopher J.},
title = {Rapid on-chip postcolumn labeling and high-resolution separations
of DNA},
journal = {ELECTROPHORESIS},
year = {2005},
volume = {26},
pages = {4729--4742},
number = {24},
abstract = {Abstract 10.1002/elps.200500459.abs When performing genetic analysis
on microfluidic systems, labeling the sample DNA for detection is
a critical preparation step. Labeling procedures often involve fluorescently
tagged primers and PCRs, which lengthen experimental run times and
introduce higher levels of complexity, increasing the overall cost
per analysis. Alternatively, on-chip labeling techniques based on
intercalating dyes permit rapid labeling of DNA fragments. However,
as noted in the literature, the stochastic nature of dye-DNA complex
formation hinders the native electrophoretic migration of DNA fragments,
degrading the separation resolution. In this study, we present a
novel method of controllably labeling DNA fragments at the end of
the electrophoretic separation channel in a glass microfluidic chip.
Permitting the DNA to separate and labeling just before detection,
achieves the rapid labeling associated with intercalators while maintaining
the high resolution of native DNA separations. Our analyses are completed
in minutes, rather than the hours typical of sample prelabeling.
We demonstrate an electrophoretic microchip-based intercalator labeling
technique that achieves higher resolution performance than reported
in the literature to date.},
issn = {1522-2683},
keywords = {Capillary electrophoresis, DNA sequencing, Intercalator, Label, Microfluidics},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200500459}
}
@ARTICLE{Sierra2010,
author = {Sierra, Beatriz and Perez, Ana B. and Vogt, Katrin and Garcia, Gissel
and Schmolke, Kathrin and Aguirre, Eglys and Alvarez, Mayling and
Kern, Florian and Kourí, Gustavo and Volk, Hans-Dieter and Guzman,
Maria G.},
title = {Secondary heterologous dengue infection risk: Disequilibrium between
immune regulation and inflammation?},
journal = {Cellular Immunology},
year = {2010},
volume = {262},
pages = {134--140},
number = {2},
abstract = {Increased serum levels of cytokines released by cells of the immune
response have been detected in patients suffering from dengue disease.
Likewise, secondary infections by a different dengue virus serotype
result in a highest risk of development of the severe dengue disease.
Both findings suggest that the memory immune response is one of the
key players in the pathogenesis of this disease. Here we take advantage
of the particular Cuban epidemiological situation in dengue to analyze
a broad spectrum of cell-mediated immune response mediators at mRNA
and protein level. Evidences for a regulatory immune pattern in homologous
(TGF-[beta], IL-10) vs. pro-inflammatory pattern (IFN-[gamma], TNF-[alpha])
in heterologous dengue virus re-challenge were found, suggesting
a possible association with the higher incidence of severe dengue
cases in the latter case.},
issn = {0008-8749},
keywords = {Cytokines, Immunopathogenesis, Dengue},
url = {http://www.sciencedirect.com/science/article/B6WCF-4YC2XJC-3/2/6b3e9036aa98fd99c41afeee9dbaf8b8}
}
@ARTICLE{Sierra2010a,
author = {Sierra, Beatriz and Perez, Ana B. and Vogt, Katrin and Garcia, Gissell
and Schmolke, Kathrin and Aguirre, Eglys and Alvarez, Mayling and
Volk, Hans-Dieter and Guzman, Maria G.},
title = {MCP-1 and MIP-1[alpha] expression in a model resembling early immune
response to dengue},
journal = {Cytokine},
year = {2010},
volume = {52},
pages = {175--183},
number = {3},
month = dec,
abstract = {Dengue virus has become endemic in most tropical urban areas throughout
the world, and DHF has appeared concomitantly with this expansion.
The intensity of dengue virus replication during the early stages
of infection could determine clinical outcomes; therefore, it is
important to understand the impact of dengue virus infection on the
earliest immune defense against microbial infection, which also strongly
regulates the adaptive immune responses. This study was aimed at
evaluating the expression of the CC-chemokines MIP-1[alpha]/CCL3
and MCP-1/CCL2 in peripheral blood leukocytes using an ex vivo model
resembling dengue infection in vivo, in subjects with a well characterized
dengue immune background, due to the exceptional Cuban epidemiological
situation in dengue. The expression of IFN[gamma], TNF[alpha] and
IL10 was also evaluated, giving insight about the role of MCP-1 and
MIP-1[alpha] in the interplay between innate and adaptive immunity.
From individuals with different dengue immune background after dengue
virus challenge, increased and different expression of the chemokines
and cytokines studied was verified in peripheral blood mononuclear
cells, thus demonstrating that the previous immunity to a dengue
virus serotype has a strong influence on the early immune response
after dengue re-infection.},
issn = {1043-4666},
keywords = {Dengue, Chemokines, Cuba, MIP-1[alpha], MCP-1},
url = {http://www.sciencedirect.com/science/article/B6WDF-50KMVS6-1/2/b32b52f60ae2109eb9c0c2074f76f1a5}
}
@ARTICLE{Sierro2009,
author = {Sierro, Nicolas and Li, Shuang and Suzuki, Yutaka and Yamashita,
Riu and Nakai, Kenta},
title = {Spatial and temporal preferences for trans-splicing in Ciona intestinalis
revealed by EST-based gene expression analysis},
journal = {Gene},
year = {2009},
volume = {430},
pages = {44--49},
number = {1-2},
month = feb,
abstract = {Ciona intestinalis is a useful model organism to analyze chordate
development and genetics. However, unlike vertebrates, it shares
a unique mechanism called trans-splicing with lower eukaryotes. In
the computational analysis of trans-splicing in C. intestinalis we
report here, we discovered that although the amount of non-trans-spliced
and trans-spliced genes is usually equivalent, the expression ratio
between the two groups varies significantly with tissues and developmental
stages. Among the seven tissues studied, the observed ratios ranged
from 2.53 in "gonad" to 19.53 in "endostyle", and during development
they increased from 1.68 at the "egg" stage to 7.55 at the "juvenile"
stage. We further hypothesize that this enrichment in trans-spliced
mRNAs in early developmental stages might be related to the abundance
of trans-spliced mRNAs in "gonad". Our analysis indicates that in
C. intestinalis, although there may not exist strong fundamental
requirements for genes to be trans-spliced, the populations of non-trans-spliced
and trans-spliced genes are likely to be spatially and temporally
regulated differently.},
issn = {0378-1119},
keywords = {EST, Regulation, Ascidian, Sequence analysis},
url = {http://www.sciencedirect.com/science/article/B6T39-4TRCYCS-2/2/db4e7e22e565a391defe4210ef72731d}
}
@ARTICLE{Sieuwerts2010a,
author = {Sieuwerts, Sander and Molenaar, Douwe and van Hijum, Sacha A.F.T.
and Beerthuyzen, Marke and Stevens, Marc J.A. and Janssen, Patrick
W.M. and Ingham, Colin J. and de Bok, Frank A.M. and de Vos, Willem
M. and van Hylckama Vlieg, Johan E.T.},
title = {Mixed culture transcriptome analysis reveals molecular basis of mixed
culture growth in Streptococcus thermophilus and Lactobacillus bulgaricus},
journal = {Appl. Envir. Microbiol.},
year = {2010},
pages = {AEM.01122-10--},
month = oct,
abstract = {Many food fermentations are carried out by mixed cultures of lactic
acid bacteria. Interactions between strains are of key importance
for the performance of these fermentations. Yoghurt fermentation
by Streptococcus thermophilus and Lactobacillus delbrueckii subsp.
bulgaricus (L. bulgaricus) is one of the best-described mixed culture
fermentations. These species are believed to stimulate each other's
growth by the exchange of metabolites such as folic acid and carbon
dioxide. Recently, post-genomic studies revealed that an upregulation
of biosynthesis pathways for nucleotides and sulfur-containing amino
acids is part of the global physiological response to mixed culture
growth in S. thermophilus, but an in-depth molecular analysis of
mixed culture growth of both strains remains to be established.Here
we report the application of mixed culture transcriptome profiling
and a systematic analysis of the effect of interaction-related compounds
on growth, which allowed us to unravel of the molecular responses
associated with batch mixed culture growth in milk of S. thermophilus
CNRZ1066 and L. bulgaricus ATCC BAA-365. The results indicate that
interactions between these bacteria are primarily related to purine,
amino acid and long-chain fatty acid metabolism. The results support
a model in which formic acid, folic acid and fatty acids are provided
by S. thermophilus. Proteolysis by L. bulgaricus supplies both strains
with amino acids but is insufficient to meet the biosynthetic demands
for sulfur and branched-chain amino acids, as becomes clear from
the upregulation of genes associated with these amino acids in mixed
culture. Moreover, genes involved in iron uptake in S. thermophilus
are affected by mixed culture growth and genes coding for exopolysaccharide
production were upregulated in both organisms in mixed culture compared
to mono-cultures.The confirmation of previously identified responses
in S. thermophilus using a different strain combination demonstrates
their generic value. In addition, the post-genomic analysis of the
responses of L. bulgaricus to mixed culture growth allows a deeper
understanding of the ecology and interactions of this important industrial
food fermentation process.},
url = {http://aem.asm.org/cgi/content/abstract/AEM.01122-10v1}
}
@ARTICLE{Sieuwerts2010,
author = {Sieuwerts, Sander and Molenaar, Douwe and van Hijum, Sacha A. F.
T. and Beerthuyzen, Marke and Stevens, Marc J. A. and Janssen, Patrick
W. M. and Ingham, Colin J. and de Bok, Frank A. M. and de Vos, Willem
M. and van Hylckama Vlieg, Johan E. T.},
title = {Mixed-Culture Transcriptome Analysis Reveals the Molecular Basis
of Mixed-Culture Growth in Streptococcus thermophilus and Lactobacillus
bulgaricus},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {7775--7784},
number = {23},
month = dec,
abstract = {Many food fermentations are performed using mixed cultures of lactic
acid bacteria. Interactions between strains are of key importance
for the performance of these fermentations. Yogurt fermentation by
Streptococcus thermophilus and Lactobacillus bulgaricus (basonym,
Lactobacillus delbrueckii subsp. bulgaricus) is one of the best-described
mixed-culture fermentations. These species are believed to stimulate
each other's growth by the exchange of metabolites such as folic
acid and carbon dioxide. Recently, postgenomic studies revealed that
an upregulation of biosynthesis pathways for nucleotides and sulfur-containing
amino acids is part of the global physiological response to mixed-culture
growth in S. thermophilus, but an in-depth molecular analysis of
mixed-culture growth of both strains remains to be established. We
report here the application of mixed-culture transcriptome profiling
and a systematic analysis of the effect of interaction-related compounds
on growth, which allowed us to unravel the molecular responses associated
with batch mixed-culture growth in milk of S. thermophilus CNRZ1066
and L. bulgaricus ATCC BAA-365. The results indicate that interactions
between these bacteria are primarily related to purine, amino acid,
and long-chain fatty acid metabolism. The results support a model
in which formic acid, folic acid, and fatty acids are provided by
S. thermophilus. Proteolysis by L. bulgaricus supplies both strains
with amino acids but is insufficient to meet the biosynthetic demands
for sulfur and branched-chain amino acids, as becomes clear from
the upregulation of genes associated with these amino acids in mixed
culture. Moreover, genes involved in iron uptake in S. thermophilus
are affected by mixed-culture growth, and genes coding for exopolysaccharide
production were upregulated in both organisms in mixed culture compared
to monocultures. The confirmation of previously identified responses
in S. thermophilus using a different strain combination demonstrates
their generic value. In addition, the postgenomic analysis of the
responses of L. bulgaricus to mixed-culture growth allows a deeper
understanding of the ecology and interactions of this important industrial
food fermentation process.},
comment = {10.1128/AEM.01122-10},
url = {http://aem.asm.org/cgi/content/abstract/76/23/7775}
}
@ARTICLE{SIEVERS2008,
author = {SIEVERS, SONJA and FRITZSCH, CARLA and KUHNEN, CORNELIUS and MULLER,
OLIVER},
title = {SPMSP: A Solid-phase PCR with Colorimetric Read-out for Quantitative
Methylation Analysis},
journal = {Anticancer Res},
year = {2008},
volume = {28},
pages = {2055--2060},
number = {4B},
month = jul,
abstract = {Background: As DNA methylation has been determined as an important
diagnostic biomarker in cancer management, methods for the detection
of quantitative DNA methylation which are high-throughput and low-cost
are needed. Materials and Methods: In this work, we introduce the
solid-phase methylation-specific PCR (SPMSP) as a method for quantitative
methylation analysis. SPMSP combines methylation-specific DNA amplification
on a solid phase with subsequent colorimetric detection in an ELISA-based
format. Results: In contrast to existing methods for quantitative
methylation analysis, SPMSP can be carried out with standard laboratory
equipment, i.e. a thermocycler and an ELISA reader. With this method,
DNA methylation in the promoter of the APC tumour suppressor gene
was quantified in a set of colorectal carcinoma samples. Conclusion:
As SPMSP can be modified to the analysis of other promoter sequences
and is also adaptable to a high-throughput system, SPMSP offers a
platform for methylation profiling with widespread applications in
cancer research and management.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/28/4B/2055}
}
@ARTICLE{Siggers2011,
author = {Siggers, Jayda and Sangild, Per T. and Jensen, Tim K. and Siggers,
Richard H. and Skovgaard, Kerstin and Stoy, Ann Cathrine F. and Jensen,
Bent B. and Thymann, Thomas and Bering, Stine B. and Boye, Mette},
title = {Transition from parenteral to enteral nutrition induces immediate
diet-dependent gut histological and immunological responses in preterm
neonates},
journal = {Am J Physiol Gastrointest Liver Physiol},
year = {2011},
volume = {301},
pages = {G435-445},
number = {3},
abstract = {Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly
from a mild intolerance to enteral feeding into intestinal mucosal
hemorrhage, inflammation, and necrosis. We hypothesized that immediate
feeding-induced gut responses precede later clinical NEC symptoms
in preterm pigs. Fifty-six preterm pigs were fed total parenteral
nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17,
or 34 h with either colostrum (Colos, n = 20) or formula (Form, n
= 31). Macroscopic NEC lesions were detected in Form pigs throughout
the enteral feeding period (20/31, 65%), whereas most Colos pigs
remained protected (1/20, 5%). Just 8 h of formula feeding induced
histopathological lesions, as evidenced by capillary stasis and necrosis,
epithelial degeneration, edema, and mucosal hemorrhage. These immediate
formula-induced changes were paralleled by decreased digestive enzyme
activities (lactase and dipeptidylpeptidase IV), increased nutrient
fermentation, and altered expression of innate immune defense genes
such as interleukins (IL-1, IL-6, IL-18), nitric oxide synthetase,
tight junction proteins (claudins), Toll-like receptors (TLR-4),
and TNF-. In contrast, the first hours of colostrum feeding induced
no histopathological lesions, increased maltase activity, and induced
changes in gene expressions related to tissue development. Total
bacterial density was high after 2 days of parenteral feeding and
was not significantly affected by diet (colostrum, formula) or length
of enteral feeding (8-34 h), except that a few bacterial groups (Clostridium,
Enterococcus, Streptococcus species) increased with time. We conclude
that a switch from parenteral to enteral nutrition rapidly induces
diet-dependent histopathological, functional, and proinflammatory
insults to the immature intestine. Great care is required when introducing
enteral feeds to TPN-fed preterm infants, particularly when using
formula, because early feeding-induced insults may predispose to
NEC lesions that are difficult to revert by later dietary or medical
interventions.},
doi = {10.1152/ajpgi.00400.2010},
eprint = {http://ajpgi.physiology.org/cgi/reprint/301/3/G435.pdf},
url = {http://ajpgi.physiology.org/cgi/content/abstract/301/3/G435}
}
@ARTICLE{Siggers2008,
author = {Siggers, Richard H. and Siggers, Jayda and Boye, Mette and Thymann,
Thomas and Molbak, Lars and Leser, Thomas and Jensen, Bent B. and
Sangild, Per T.},
title = {Early Administration of Probiotics Alters Bacterial Colonization
and Limits Diet-Induced Gut Dysfunction and Severity of Necrotizing
Enterocolitis in Preterm Pigs},
journal = {J. Nutr.},
year = {2008},
volume = {138},
pages = {1437--1444},
number = {8},
month = aug,
abstract = {Following preterm birth, bacterial colonization and enteral formula
feeding predispose neonates to gut dysfunction and necrotizing enterocolitis
(NEC), a serious gastrointestinal inflammatory disease. We hypothesized
that administration of probiotics would beneficially influence early
bacterial colonization, thereby reducing the susceptibility to formula-induced
gut atrophy, dysfunction, and NEC. Caesarean-delivered preterm pigs
were provided total parenteral nutrition (1.5 d) followed by enteral
feeding (2 d) with porcine colostrum (COLOS; n = 5), formula (FORM;
n = 9), or formula with probiotics (FORM-P; Bifidobacterium animalis
and Lactobacillus: L. acidophilus, L. casei, L. pentosus, L. plantarum;
n = 13). Clinical NEC scores were reduced (P < 0.05) in FORM-P (2.0
{+/-} 0.2) and COLOS groups (1.7 {+/-} 0.5) compared with FORM pigs
(3.4 {+/-} 0.6). Lower NEC scores were associated with elevated intestinal
weight, mucosa proportion, villus height, RNA integrity, and brush
border aminopeptidase A and N activities, and lower gastric organic
acid concentration in the FORM-P and COLOS groups (P < 0.05). Diversity
of the mucosa-associated bacteria in the distal small intestine was
similar among formula-fed pigs, yet the abundance of specific bacterial
groups differed between FORM-P and FORM pigs. FORM-P pigs had lower
colonization density of a potential pathogen, Clostridium perfringens,
and had commensal Lactobacillus bacteria more closely associated
with enterocytes along the villus-crypt axis relative to FORM pigs.
These results suggest that probiotic administration immediately after
birth promotes the colonization of a beneficial commensal microbiota
capable of limiting the formula-induced mucosal atrophy, dysfunction,
and pathogen load in preterm neonates, thereby reducing the incidence
and severity of NEC.},
url = {http://jn.nutrition.org/cgi/content/abstract/138/8/1437}
}
@ARTICLE{Sigoillot2010,
author = {Sigoillot, Severine M. and Bourgeois, Francine and Lambergeon, Monique
and Strochlic, Laure and Legay, Claire},
title = {ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction},
journal = {J. Neurosci.},
year = {2010},
volume = {30},
pages = {13--23},
number = {1},
month = jan,
abstract = {CollagenQ (ColQ) plays an important structural role at vertebrate
neuromuscular junctions (NMJs) by anchoring and accumulating acetylcholinesterase
(AChE) in the extracellular matrix (ECM). Moreover, ColQ interacts
with perlecan/dystroglycan and the muscle-specific receptor tyrosine
kinase (MuSK), key molecules in the NMJ formation. MuSK promotes
acetylcholine receptor (AChR) clustering in a process mediated by
rapsyn, a cytoplasmic protein that stimulates AChR packing in clusters
and regulates synaptic gene transcription. Here, we investigated
a regulatory role for ColQ by comparing the clustering and expression
of synaptic proteins in wild type and ColQ-deficient muscle cells
in culture and at NMJ. We show first that AChR clusters are smaller
and more densely packed in the absence of ColQ both in vitro and
in vivo. Second, we find that like AChRs and rapsyn, MuSK mRNA levels
are increased in cultured cells but not in muscles lacking ColQ.
However, membrane-bound MuSK is decreased both in vitro and in vivo
suggesting that ColQ controls MuSK sorting or stabilization in the
muscle membrane. In line with this, our data show that activation
of the MuSK signaling pathway is altered in the absence of ColQ leading
to (1) perturbation of AChR clustering and/or {beta}-AChR subunit
phosphorylation and (2) modifications of AChR mRNA level due to the
lack of ColQ-MuSK interaction. Together, our results demonstrate
that ColQ, in addition to its structural role, has important regulatory
functions at the synapse by controlling AChR clustering and synaptic
gene expression through its interaction with MuSK.},
url = {http://www.jneurosci.org/cgi/content/abstract/30/1/13}
}
@ARTICLE{Sigoillot2010a,
author = {Sigoillot, Séverine M. and Bourgeois, Francine and Legay, Claire},
title = {Cholinesterases regulation in the absence of ColQ},
journal = {Chemico-Biological Interactions},
year = {2010},
volume = {187},
pages = {84--89},
number = {1-3},
month = sep,
abstract = {Normal physiological activity of the neuromuscular junction (NMJ)
requires that key molecules are clustered at the synapse. One of
these molecules is acetylcholinesterase (AChE) that regulates acetylcholine
levels. This enzyme exists under different isoforms but the predominant
form at the NMJ is a collagen-tailed enzyme. The collagen associated
to AChE (ColQ) fulfills two functions. It anchors and accumulates
AChE in the extracellular matrix. Mutations in ColQ lead to faint
or no activity of AChE in the synaptic cleft. As a consequence, normal
NMJ functioning is impaired and myasthenic syndromes are observed
in patients bearing these mutations. Here, we investigated the effects
of ColQ deficiency on cholinesterases mRNA levels and cluster formation.
We show that overexpression of AChE but not ColQ in muscle cells
is sufficient to drive the formation of AChE clusters. The absence
of ColQ in muscle cells in vitro and in vivo leads to an increase
in AChER and AChET mRNAs, corresponding to two isoforms of AChE.
However, AChE activity is decreased in the medium of ColQ-deficient
cells suggesting that AChE secretion is impaired. Butyrylcholinesterase
(BChE) mRNAs are also upregulated in vivo. Since AChE and BChE can
associate with PRiMA, a membrane anchor, we explored the pattern
of expression of PRiMA in vitro and in vivo. The level of PRiMA transcripts
is downregulated in the absence of ColQ. Therefore, AChE, BChE and
PRiMA mRNA level modifications found in the absence of ColQ cannot
compensate for the physiological defects observed at the ColQ-deficient
NMJs.},
booktitle = {10th International Meeting on Cholinesterases},
issn = {0009-2797},
keywords = {Neuromuscular junction, ColQ, Cholinesterases, Nicotinic acetylcholine
receptor, PRiMA, MLCL},
url = {http://www.sciencedirect.com/science/article/B6T56-4YC80VM-2/2/11cd28480e77398b7851dedb4821a1bb}
}
@ARTICLE{Sikorsky2004,
author = {Sikorsky, Jan A. and Primerano, Donald A. and Fenger, Terry W. and
Denvir, James},
title = {Effect of DNA damage on PCR amplification efficiency with the relative
threshold cycle method},
journal = {Biochemical and Biophysical Research Communications},
year = {2004},
volume = {323},
pages = {823--830},
number = {3},
month = oct,
abstract = {Polymerase stop assays used to quantify DNA damage assume that single
lesions are sufficient to block polymerase progression. To test the
effect of specific lesions on PCR amplification efficiency, we amplified
synthetic 90 base oligonucleotides containing normal or modified
DNA bases using real-time PCR and determined the relative threshold
cycle amplification efficiency of each template. We found that while
the amplification efficiencies of templates containing a single 8-oxo-7,8-dihydro-2'-deoxyguanosine
(8-oxodG) were not significantly perturbed, the presence of a single
8-oxo-7,8-dihydro-2'-deoxyadenosine, abasic site, or a cis-syn thymidine
dimer dramatically reduced amplification efficiency. In addition,
while templates containing two 8-oxodGs separated by 13 bases amplified
as well as the unmodified template, the presence of two tandem 8-oxodGs
substantially hindered amplification. From these findings, we conclude
that the reduction in polymerase progression is dependent on the
type of damage and the relative position of lesions within the template.},
issn = {0006-291X},
keywords = {DNA damage, Base modification, Taq polymerase, Real-time PCR, Amplification
efficiency},
url = {http://www.sciencedirect.com/science/article/B6WBK-4D98VWW-G/2/e90d195b615556e4c60a093cc109e310}
}
@ARTICLE{Silkworth2008,
author = {Silkworth, Jay B. and Carlson, Erik A. and McCulloch, Colin and Illouz,
Kati and Goodwin, Shirlean and Sutter, Thomas R.},
title = {Toxicogenomic Analysis of Gender, Chemical, and Dose Effects in Livers
of TCDD- or Aroclor 1254-Exposed Rats Using a Multifactor Linear
Model},
journal = {Toxicol. Sci.},
year = {2008},
volume = {102},
pages = {291--309},
number = {2},
month = apr,
abstract = {Chronic exposure of Sprague-Dawley (SD) rats to either 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) or Aroclor 1254 results in female-selective induction of hepatic
tumors. The relative potency of dioxins and polychlorinated biphenyl
mixtures, such as Aroclor 1254, is often estimated using the internationally
endorsed toxic equivalency (TEQ) approach. Comparing the genome wide
changes in gene expression in both genders following exposure to
TEQ doses of these chemicals should identify critical sets of early
response genes while further defining the concept of the TEQ of halogenated
aromatic hydrocarbons. Aroclor 1254 at 0.6, 6.0, and 60 mg/kg body
weight and TEQ doses of TCDD (0.3 and 3.0 {micro}g/kg), calculated
to match the top two Aroclor 1254 doses, were orally administered
to SD rats for three consecutive days. Day 4 gene expression in hepatic
tissue was determined using microarrays. A linear mixed-effects statistical
model was developed to analyze the data in relation to treatment,
gender, and gender * treatment (G*T) interactions. The genes most
changed included 54 genes with and 51 genes without a significant
model G*T term. The known aryl hydrocarbon receptor (AHR) battery
genes (Cyp1a1, Cyp1a2, Cyp1b1, Aldh3a1), and novel genes, responded
in a TEQ dose-dependent manner in both genders. However, an important
observation was the apparent disruption of sexually dimorphic basal
gene expression, particularly for female rats. Because many of these
genes are involved in steroid metabolism, exposure to either TCDD
or Aroclor 1254 could disrupt proliferative signals more in female
rats as a possible consequence of altered estrogen metabolism. This
study extends the findings of previous rodent bioassays by identifying
groups of genes, other than the well-characterized AHR response genes,
whose disruption may be important in the tumorigenic mechanism in
this rat strain.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/102/2/291}
}
@ARTICLE{Silva2008,
author = {da Silva, Alexandre A. and do Carmo, Jussara M. and Kanyicska, Bela
and Dubinion, John and Brandon, Elizabeth and Hall, John E.},
title = {Endogenous Melanocortin System Activity Contributes to the Elevated
Arterial Pressure in Spontaneously Hypertensive Rats},
journal = {Hypertension},
year = {2008},
volume = {51},
pages = {884--890},
number = {4},
month = apr,
abstract = {Previous studies suggest that activation of the CNS melanocortin system
reduces appetite while increasing sympathetic activity and arterial
pressure. The present study tested whether endogenous activity of
the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated
arterial pressure in the spontaneously hypertensive rat (SHR), a
model of hypertension with increased sympathetic activity. A cannula
was placed in the lateral ventricle of male SHR and Wistar (WKY)
rats for chronic intracerebroventricular (ICV) infusions (0.5 {micro}L/h).
Mean arterial pressure (MAP) and heart rate (HR) were recorded 24
hour/d using telemetry. After 5-day control period, rats were infused
with MC3/4-R antagonist (SHU-9119, 1 nmol/h-ICV) for 12 days, followed
by 5-day posttreatment period. MC3/4-R antagonism increased food
intake in SHR by 90% and in WKY by 125%, resulting in marked weight
gain, insulin resistance, and hyperleptinemia in SHR and WKY. Despite
weight gain, MC3/4-R antagonism reduced HR in SHR and WKY ({approx}40
bpm), while lowering MAP to a greater extent in SHR (-22{+/-}4 mm
Hg) than WKY (-4{+/-}3 mm Hg). SHU9119 treatment failed to cause
further reductions in MAP during chronic adrenergic blockade with
propranolol and terazosin. These results suggest that endogenous
activity of the CNS melanocortin system contributes to the maintenance
of adrenergic tone and elevated arterial pressure in SHR even though
mRNA levels for POMC and MC4R in the mediobasal hypothalamus were
not increased compared to WKY. These results also support the hypothesis
that weight gain does not raise arterial pressure in the absence
of a functional MC3/4-R.},
url = {http://hyper.ahajournals.org/cgi/content/abstract/51/4/884}
}
@ARTICLE{Silva2011,
author = {Silva, A. P. and Miranda, I. M. and Guida, A. and Synnott, J. and
Rocha, R. and Silva, R. and Amorim, A. and Pina-Vaz, C. and Butler,
G. and Rodrigues, A. G.},
title = {Transcriptional Profiling of Azole-Resistant Candida parapsilosis
Strains},
journal = {Antimicrob. Agents Chemother.},
year = {2011},
volume = {55},
pages = {3546-3556},
number = {7},
abstract = {Herein we describe the changes in the gene expression profile of Candida
parapsilosis associated with the acquisition of experimentally induced
resistance to azole antifungal drugs. Three resistant strains of
C. parapsilosis were obtained following prolonged in vitro exposure
of a susceptible clinical isolate to constant concentrations of fluconazole,
voriconazole, or posaconazole. We found that after incubation with
fluconazole or voriconazole, strains became resistant to both azoles
but not to posaconazole, although susceptibility to this azole decreased,
whereas the strain incubated with posaconazole displayed resistance
to the three azoles. The resistant strains obtained after exposure
to fluconazole and to voriconazole have increased expression of the
transcription factor MRR1, the major facilitator transporter MDR1,
and several reductases and oxidoreductases. Interestingly, and similarly
to what has been described in C. albicans, upregulation of MRR1 and
MDR1 is correlated with point mutations in MRR1 in the resistant
strains. The resistant strain obtained after exposure to posaconazole
shows upregulation of two transcription factors (UPC2 and NDT80)
and increased expression of 13 genes involved in ergosterol biosynthesis.
This is the first study addressing global molecular mechanisms underlying
azole resistance in C. parapsilosis; the results suggest that similarly
to C. albicans, tolerance to azoles involves the activation of efflux
pumps and/or increased ergosterol synthesis.},
doi = {10.1128/AAC.01127-10},
eprint = {http://aac.asm.org/cgi/reprint/55/7/3546.pdf},
url = {http://aac.asm.org/cgi/content/abstract/55/7/3546}
}
@ARTICLE{Silva2009,
author = {Silva, Fernando P. G. and Swagemakers, Sigrid M. A. and Erpelinck-Verschueren,
Claudia and Wouters, Bas J. and Delwel, Ruud and Vrieling, Harry
and van der Spek, Peter and Valk, Peter J. M. and Giphart-Gassler,
Micheline},
title = {Gene expression profiling of minimally differentiated acute myeloid
leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status},
journal = {Blood},
year = {2009},
volume = {114},
pages = {3001--3007},
number = {14},
month = oct,
abstract = {Minimally differentiated acute myeloid leukemia (AML-M0) is defined
by immature morphology and expression of early hematologic markers.
By gene expression profiling (GEP) and subsequent unsupervised analysis
of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate
that AML-M0 cases express a unique signature that is largely separated
from other molecular subtypes. Hematologic transcription regulators
such as CEBPA, CEBPD, and ETV6, and the differentiation associated
gene MPO appeared strongly down-regulated, in line with the primitive
state of this leukemia. AML-M0 frequently carries loss-of-function
RUNX1 mutation. Unsupervised analyses revealed a subdivision between
AML-M0 cases with and without RUNX1 mutations. RUNX1 mutant AML-M0
samples showed a distinct up-regulation of B cell-related genes such
as members of the B-cell receptor complex, transcription regulators
RUNX3, ETS2, IRF8, or PRDM1, and major histocompatibility complex
class II genes. Importantly, prediction with high accuracy of the
AML-M0 subtype and prediction of patients carrying RUNX1 mutation
within this subtype were possible based on the expression level of
only a few transcripts. We propose that RUNX1 mutations in this AML
subgroup cause lineage infidelity, leading to aberrant coexpression
of myeloid and B-lymphoid genes. Furthermore, our results imply that
AML-M0, although originally determined by morphology, constitutes
a leukemia subgroup.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/14/3001}
}
@ARTICLE{Silva2011a,
author = {Silva, Ines N. and Ferreira, Ana S. and Becker, Jorg D. and Zlosnik,
James E. A. and Speert, David P. and He, Ji and Mil-Homens, Dalila
and Moreira, Leonilde M.},
title = {Mucoid morphotype variation of Burkholderia multivorans during chronic
cystic fibrosis lung infection is correlated with changes in metabolism,
motility, biofilm formation and virulence},
journal = {Microbiology},
year = {2011},
volume = {157},
pages = {3124-3137},
number = {11},
abstract = {Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens
infecting hosts such as cystic fibrosis (CF) patients. Long-term
Bcc infection of CF patients' airways has been associated with emergence
of phenotypic variation. Here we studied two Burkholderia multivorans
clonal isolates displaying different morphotypes from a chronically
infected CF patient to evaluate trait development during lung infection.
Expression profiling of mucoid D2095 and non-mucoid D2214 isolates
revealed decreased expression of genes encoding products related
to virulence-associated traits and metabolism in D2214. Furthermore,
D2214 showed no exopolysaccharide production, lower motility and
chemotaxis, and more biofilm formation, particularly under microaerophilic
conditions, than the clonal mucoid isolate D2095. When Galleria mellonella
was used as acute infection model, D2214 at a cell number of approximately
7x106 c.f.u. caused a higher survival rate than D2095, although 6
days post-infection most of the larvae were dead. Infection with
the same number of cells by mucoid D2095 caused larval death by day
4. The decreased expression of genes involved in carbon and nitrogen
metabolism may reflect lower metabolic needs of D2214 caused by lack
of exopolysaccharide, but also by the attenuation of pathways not
required for survival. As a result, D2214 showed higher survival
than D2095 in minimal medium for 28 days under aerobic conditions.
Overall, adaptation during Bcc chronic lung infections gave rise
to genotypic and phenotypic variation among isolates, contributing
to their fitness while maintaining their capacity for survival in
this opportunistic human niche.},
doi = {10.1099/mic.0.050989-0},
eprint = {http://mic.sgmjournals.org/cgi/reprint/157/11/3124.pdf},
url = {http://mic.sgmjournals.org/cgi/content/abstract/157/11/3124}
}
@ARTICLE{Silva2008a,
author = {Silva, L.F.P. and Etchebarne, B.E. and Weber Nielsen, M.S. and Liesman,
J.S. and Kiupel, M. and VandeHaar, M.J.},
title = {Intramammary Infusion of Leptin Decreases Proliferation of Mammary
Epithelial Cells in Prepubertal Heifers},
journal = {Journal of Dairy Science},
year = {2008},
volume = {91},
pages = {3034--3044},
number = {8},
month = aug,
abstract = {High energy intake and excessive body fatness impair mammogenesis
in prepubertal ruminants. High energy intake and excessive fatness
also increase serum leptin. Our objective was to determine if an
infusion of leptin decreases proliferation of mammary epithelial
cells of prepubertal heifers in vivo. Ovine leptin at 100 [mu]g/quarter
per d with or without 10 [mu]g of insulin-like growth factor (IGF)-I
was infused via the teat canal into mammary glands of prepubertal
dairy heifers; contralateral quarters were used as controls. After
7 d of treatment, bromodeoxyuridine was infused intravenously and
heifers were slaughtered ~2 h later. Tissue from 3 regions of the
mammary parenchyma was collected and immunostained for bromodeoxyuridine
(BrdU), proliferating cell nuclear antigen (Ki-67), and caspase-3.
Leptin decreased the number of mammary epithelial cells in the S-phase
of the cell cycle by 48% in IGF-I-treated quarters and by 19% in
saline-treated quarters. Leptin did not alter the number of mammary
epithelial cells within the cell cycle, as indicated by Ki-67 labeling.
Caspase-3 immunostaining within the mammary parenchyma was very low
in these heifers, but leptin significantly increased labeling in
saline-treated quarters. Leptin enhanced SOCS-3 expression in IGF-I-treated
quarters but did not alter SOCS-1 or SOCS-5 expression. We conclude
that a high concentration of leptin in the bovine mammary gland reduces
proliferation of mammary epithelial cells. The reduced proliferation
is accompanied by an increase in SOCS-3 expression, suggesting a
possible mechanism for leptin inhibition of IGF-I action. Whether
leptin might be a physiological regulator of mammogenesis remains
to be determined.},
issn = {0022-0302},
keywords = {mammary gland, leptin, insulin-like growth factor-I, proliferation},
url = {http://www.sciencedirect.com/science/article/B9887-4YBNWSX-D/2/25715c22b01900921bcd598931652fca}
}
@ARTICLE{Silva2011b,
author = {Silva, Mariana and De Souza, Alessandra and Takita, Marco and Labate,
Carlos and Machado, Marcos},
title = {Analysis of the biofilm proteome of Xylella fastidiosa},
journal = {Proteome Science},
year = {2011},
volume = {9},
pages = {58},
number = {1},
abstract = {BACKGROUND:Xylella fastidiosa is limited to the xylem of the plant
host and the foregut of insect vectors (sharpshooters). The mechanism
of pathogenicity of this bacterium differs from other plant pathogens,
since it does not present typical genes that confer specific interactions
between plant and pathogens (avr and/or hrp). The bacterium is injected
directly into the xylem vessels where it adheres and colonizes. The
whole process leads to the formation of biofilms, which are considered
the main mechanism of pathogenicity. Cells in biofilms are metabolically
and phenotypically different from their planktonic condition. The
mature biofilm stage (phase of higher cell density) presents high
virulence and resistance to toxic substances such as antibiotics
and detergents. Here we performed proteomic analysis of proteins
expressed exclusively in the mature biofilm of X. fastidiosa strain
9a5c, in comparison to planktonic growth condition.RESULTS:We found
a total of 456 proteins expressed in the biofilm condition, which
correspond to approximately 10% of total protein in the genome. The
biofilm showed 37% (or 144 proteins) different protein than we found
in the planktonic growth condition. The large difference in protein
pattern in the biofilm condition may be responsible for the physiological
changes of the cells in the biofilm of X. fastidiosa. Mass spectrometry
was used to identify these proteins, while real-time quantitative
polymerase chain reaction monitored expression of genes encoding
them. Most of proteins expressed in the mature biofilm growth were
associated with metabolism, adhesion, pathogenicity and stress conditions.
Even though the biofilm cells in this work were not submitted to
any stress condition, some stress related proteins were expressed
only in the biofilm condition, suggesting that the biofilm cells
would constitutively express proteins in different adverse environments.CONCLUSIONS:We
observed overexpression of proteins related to quorum sensing, proving
the existence of communication between cells, and thus the development
of structuring the biofilm (mature biofilm) leading to obstruction
of vessels and development of disease. This paper reports a first
proteomic analysis of mature biofilm of X. fastidiosa, opening new
perspectives for understanding the biochemistry of mature biofilm
growth in a plant pathogen.},
doi = {10.1186/1477-5956-9-58},
issn = {1477-5956},
pubmedid = {21939513},
url = {http://www.proteomesci.com/content/9/1/58}
}
@ARTICLE{SilveiraMitteldorf2011,
author = {da Silveira Mitteldorf, Cristina Aparecida Troques and de Sousa-Canavez,
Juliana Moreira and Leite, Kátia Ramos Moreira and Massumoto, Celso
and Camara-Lopes, Luis Heraldo},
title = {FN1, GALE, MET, and QPCT overexpression in papillary thyroid carcinoma:
Molecular analysis using frozen tissue and routine fine-needle aspiration
biopsy samples},
journal = {Diagnostic Cytopathology},
year = {2011},
volume = {39},
pages = {556--561},
number = {8},
abstract = {Thyroid nodules are a common clinical problem, and fine-needle aspiration
biopsy (FNAB) is widely used for its evaluation. Only 5% are malignant,
being papillary carcinoma (PC) the most frequent neoplasia. Approximately
20% are classified as indeterminate or suspicious for malignancy.
Gene-expression pattern may be useful for diagnosing PC in difficult
or ambiguous cases. In our prior study, we were able to apply RT-PCR
method in a series of routinely performed FNAB of thyroid nodules
using individual, residual samples. In this study, a total of 70
thyroid samples were evaluated for the expression of MPPED2, H/HBA2,
MET, FN1, GALE, and QPCT genes, including 24 cases of frozen thyroid
tissue, 12 nodular hyperplasia and 12 PC, and the 46 consecutive
thyroid FNAB samples, previously analyzed (3 positive, 10 indeterminate
and 32 negative for malignancy, and 1 insufficient). FN1, GALE, MET,
and QPCT mRNA expression were significantly different in benign and
malignant samples, with similar pattern of overexpression in aspirates
compared to frozen tissue. H/HBA2 and MPPED2 expression varied. Histological
correlation was possible in five indeterminate cases, revealing one
PC and four benign lesions. In conclusion, FN1, GALE, MET, and QPCT
were significantly overexpressed in thyroid PC. RT-PCR method could
be applied to routine FNAB, showing a similar pattern of overexpression.
Despite the small number of cases evaluated, our results suggest
that molecular analysis may be of assistance in patients with indeterminate/suspicious
cytology, adding elements for preoperative diagnosis and better management
of these patients. Diagn. Cytopathol. 2011. © 2010 Wiley-Liss, Inc.},
doi = {10.1002/dc.21423},
issn = {1097-0339},
keywords = {thyroid nodules, papillary carcinoma, RT-PCR, FNAB, molecular analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/dc.21423}
}
@ARTICLE{SilveiraMitteldorf2008,
author = {da Silveira Mitteldorf, Cristina Aparecida Troques and de Sousa-Canavez,
Juliana Moreira and Massumoto, Celso and da Camara-Lopes, Luis Heraldo},
title = {Fine-needle aspiration biopsy of thyroid nodules as a possible source
for molecular studies: Analysis of RNA obtained from routine cases},
journal = {Diagn. Cytopathol.},
year = {2008},
volume = {36},
pages = {899--903},
number = {12},
abstract = {Abstract 10.1002/dc.20939.abs Thyroid nodules are frequent in clinical
practice and fine-needle aspiration biopsy (FNAB) is widely used
for its evaluation, but approximately 20% of the cases are diagnosed
as indeterminate for malignancy. Aspirates from thyroid nodules can
be used for ancillary methods, but molecular techniques are not routinely
applied to these specimens. Forty-six consecutive, routinely performed,
FNAB of thyroid nodules were evaluated for the feasibility of applying
RT-PCR method. RNA was extracted from 1 of 3 fresh residual samples
and analyzed to determine its pureness, integrity, and concentration.
Cellularity was adequate in all 46, except one, specimens analyzed,
scored as 0, 1+, 2+, 3+, and 4+ in 1, 10, 14, 9, and 8 cases, respectively.
Thirty-three nodules measured less than 1.5 cm. Cytological diagnosis
was positive for malignancy in 3 cases, indeterminate for malignancy
in 3, most probably benign follicular lesion in 7, negative for malignancy
in 32, and suggestive of benign follicular lesion in 1. Good quality
RNA was successfully isolated in 45/46 (97.8%) samples, with an average
RNA concentration of 14 ng/μl and detection of B2M mRNA in 97.7%
(44/45). There was no significant correlation between RNA concentration
and nodule size or specimen cellularity. In conclusion, molecular
analysis using individual, residual samples of thyroid nodules aspirates
is feasible and could be employed for molecular preoperative studies
in the future, adding elements for final cytological diagnosis of
indeterminate cases, without altering the routine procedure. Diagn.
Cytopathol. 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-0339},
keywords = {thyroid nodules, fine-needle aspiration biopsy, routine cytological
specimens, molecular analysis, RT-PCR},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/dc.20939}
}
@ARTICLE{Silveira2010,
author = {Silveira, Alexandra C. and Morrison, Margaux A. and Ji, Fei and Xu,
Haiyan and Reinecke, James B. and Adams, Scott M. and Arneberg, Trevor
M. and Janssian, Maria and Lee, Joo-Eun and Yuan, Yang and Schaumberg,
Debra A. and Kotoula, Maria G. and Tsironi, Evangeline E. and Tsiloulis,
Aristoteles N. and Chatzoulis, Dimitrios Z. and Miller, Joan W. and
Kim, Ivana K. and Hageman, Gregory S. and Farrer, Lindsay A. and
Haider, Neena B. and DeAngelis, Margaret M.},
title = {Convergence of linkage, gene expression and association data demonstrates
the influence of the RAR-related orphan receptor alpha (RORA) gene
on neovascular AMD: A systems biology based approach},
journal = {Vision Research},
year = {2010},
volume = {50},
pages = {698--715},
number = {7},
month = mar,
abstract = {To identify novel genes and pathways associated with AMD, we performed
microarray gene expression and linkage analysis which implicated
the candidate gene, retinoic acid receptor-related orphan receptor
alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide
polymorphisms (SNPs) in a family-based cohort, followed by replication
in an unrelated case-control cohort, demonstrated that SNPs and haplotypes
located in intron 1 were significantly associated with neovascular
AMD risk in both cohorts. This is the first report demonstrating
a possible role for RORA, a receptor for cholesterol, in the pathophysiology
of AMD. Moreover, we found a significant interaction between RORA
and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD
pathophysiology.},
booktitle = {Mechanisms in Macular Degeneration},
issn = {0042-6989},
keywords = {Neovascularization, RORA, Single nucleotide polymorphisms, Haplotypes,
Linkage, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T0W-4X9TTRG-1/2/d6b3aac2caa34fce24e86fa728f7f28f}
}
@ARTICLE{Silver2008,
author = {Silver, Nicholas and Cotroneo, Emanuele and Proctor, Gordon and Osailan,
Samira and Paterson, Katherine and Carpenter, Guy},
title = {Selection of housekeeping genes for gene expression studies in the
adult rat submandibular gland under normal, inflamed, atrophic and
regenerative states},
journal = {BMC Molecular Biology},
year = {2008},
volume = {9},
pages = {64},
number = {1},
abstract = {BACKGROUND:Real-time PCR is a reliable tool with which to measure
mRNA transcripts, and provides valuable information on gene expression
profiles. Endogenous controls such as housekeeping genes are used
to normalise mRNA levels between samples for sensitive comparisons
of mRNA transcription. Selection of the most stable control gene(s)
is therefore critical for the reliable interpretation of gene expression
data. For the purpose of this study, 7 commonly used housekeeping
genes were investigated in salivary submandibular glands under normal,
inflamed, atrophic and regenerative states.RESULTS:The program NormFinder
identified the suitability of HPRT to use as a single gene for normalisation
within the normal, inflamed and regenerative states, and GAPDH in
the atrophic state. For normalisation to multiple housekeeping genes,
for each individual state, the optimal number of housekeeping genes
as given by geNorm was: ACTB/UBC in the normal, ACTB/YWHAZ in the
inflamed, ACTB/HPRT in the atrophic and ACTB/GAPDH in the regenerative
state. The most stable housekeeping gene identified between states
(compared to normal) was UBC. However, ACTB, identified as one of
the most stably expressed genes within states, was found to be one
of the most variable between states. Furthermore we demonstrated
that normalising between states to ACTB, rather than UBC, introduced
an approximately 3 fold magnitude of error.CONCLUSION:Using NormFinder,
our studies demonstrated the suitability of HPRT to use as a single
gene for normalisation within the normal, inflamed and regenerative
groups and GAPDH in the atrophic group. However, if normalising to
multiple housekeeping genes, we recommend normalising to those identified
by geNorm. For normalisation across the physiological states, we
recommend the use of UBC.},
doi = {10.1186/1471-2199-9-64},
issn = {1471-2199},
pubmedid = {18637167},
url = {http://www.biomedcentral.com/1471-2199/9/64}
}
@ARTICLE{Silverman2003,
author = {Silverman, Neal and Zhou, Rui and Erlich, Rachel L. and Hunter, Mike
and Bernstein, Erik and Schneider, David and Maniatis, Tom},
title = {Immune Activation of NF-{kappa}B and JNK Requires Drosophila TAK1},
journal = {J. Biol. Chem.},
year = {2003},
volume = {278},
pages = {48928--48934},
number = {49},
month = dec,
abstract = {Stimulation of the Drosophila immune response activates NF-{kappa}B
and JNK signaling pathways. For example, infection by Gram-negative
bacteria induces the Imd signaling pathway, leading to the activation
of the NF-{kappa}B-like transcription factor Relish and the expression
of a battery of genes encoding antimicrobial peptides. Bacterial
infection also activates the JNK pathway, but the role of this pathway
in the immune response has not yet been established. Genetic experiments
suggest that the Drosophila homolog of the mammalian MAPK kinase
kinase, TAK1 (transforming growth factor {beta}-activated kinase
1), activates both the JNK and NF-{kappa}B pathways following immune
stimulation. In this report, we demonstrate that Drosophila TAK1
functions as both the Drosophila I{kappa}B kinase-activating kinase
and the JNK kinase-activating kinase. However, we found that JNK
signaling is not required for antimicrobial peptide gene expression
but is required for the activation of other immune inducible genes,
including Punch, sulfated, and malvolio. Thus, JNK signaling appears
to play an important role in the cellular immune response and the
stress response.},
url = {http://www.jbc.org/cgi/content/abstract/278/49/48928}
}
@ARTICLE{Silveyra2011,
author = {Silveyra, Patricia and Raval, Manmeet and Simmons, Brett and DiAngelo,
Susan and Wang, Guirong and Floros, Joanna},
title = {The untranslated exon B of human surfactant protein A2 mRNAs is an
enhancer for transcription and translation},
journal = {Am J Physiol Lung Cell Mol Physiol},
year = {2011},
volume = {301},
pages = {L795-803},
number = {5},
abstract = {Two human genes, SFTPA1 (SP-A1) and SFTPA2 (SP-A2), encode surfactant
protein A, a molecule of innate immunity and surfactant-related functions.
Several genetic variants have been identified for both genes. These
include nucleotide (nt) polymorphisms, as well as alternative splicing
patterns at the 5' untranslated region (5'UTR). Exon B (eB) is included
in the 5'UTR of most SP-A2, but not SP-A1 splice variants. We investigated
the role of eB in the regulation of gene expression and translation
efficiency. A luciferase (Luc) reporter gene was cloned downstream
of the entire (AeBD) or eB deletion mutants (del_mut) of the SP-A2
5'UTR, or heterologous 5'UTRs containing the eB sequence, or a random
sequence of equal length. The del_mut constructs consisted in consecutive
deletions of five nucleotides (n = 8) within eB and the exon-exon
junctions in the AeBD 5'UTR. Luc activities and mRNA levels were
compared after transfection of NCI-H441 cells. We found that 1) eB
increased Luc mRNA levels when placed upstream of heterologous 5'UTR
sequences or the promoter region, regardless of its position and
orientation; 2) translation efficiency of in vitro-generated mRNAs
containing eB was higher than that of mRNAs without eB; and 3) the
integrity of eB sequence is crucial for transcription and translation
of the reporter gene. Thus eB 1) is a transcription enhancer, because
it increases mRNA content regardless of position and orientation,
2) enhances translation when placed in either orientation within
its natural 5'UTR sequence and in heterologous 5'UTRs, and 3) contains
potential regulatory elements for both transcription and translation.
We conclude that eB sequence and length are determinants of transcription
and translation efficiency.},
doi = {10.1152/ajplung.00439.2010},
eprint = {http://ajplung.physiology.org/cgi/reprint/301/5/L795.pdf},
url = {http://ajplung.physiology.org/cgi/content/abstract/301/5/L795}
}
@ARTICLE{Sim2006,
author = {Sim, Fraser J. and Keyoung, H. Michael and Goldman, James E. and
Kim, Dong Kyu and Jung, Hee-Won and Roy, Neeta S. and Goldman, Steven
A.},
title = {Neurocytoma Is a Tumor of Adult Neuronal Progenitor Cells},
journal = {J. Neurosci.},
year = {2006},
volume = {26},
pages = {12544--12555},
number = {48},
month = nov,
abstract = {Central neurocytoma (CN) is a rare periventricular tumor, whose derivation,
lineage potential, and molecular regulation have been mostly unexplored.
We noted that CN cells exhibited an antigenic profile typical of
neuronal progenitor cells in vivo, yet in vitro generated neurospheres,
divided in response to bFGF (basic fibroblast growth factor), activated
the neuroepithelial enhancer of the nestin gene, and gave rise to
both neuron-like cells and astrocytes. When CN gene expression was
compared with that of both normal adult VZ (ventricular zone) and
E/nestin:GFP (green fluorescent protein)-sorted native neuronal progenitors,
significant overlap was noted. Marker analysis suggested that the
gene expression pattern of CN was that of a proneuronal population;
glial markers were conspicuously absent, suggesting that the emergence
of astroglia from CN occurred only with passage. The expression pattern
of CN was distinguished from that of native progenitor cells by a
cohort of differentially expressed genes potentially involved in
both the oncogenesis and phenotypic restriction of neurocytoma. These
included both IGF2 and several components of its signaling pathway,
whose sharp overexpression implicated dysregulated autocrine IGF2
signaling in CN oncogenesis. Both receptors and effectors of canonical
wnt signaling, as well as GDF8 (growth differentiation factor 8),
PDGF-D, and neuregulin, were differentially overexpressed by CN,
suggesting that CN is characterized by the concurrent overactivation
of these pathways, which may serve to drive neurocytoma expansion
while restricting tumor progenitor phenotype. This strategy of comparing
the gene expression of tumor cells to that of the purified native
progenitors from which they derive may provide a focused approach
to identifying transcripts important to stem and progenitor cell
oncogenesis.},
url = {http://www.jneurosci.org/cgi/content/abstract/26/48/12544}
}
@ARTICLE{Simandi2010,
author = {Simandi, Zoltan and Balint, Balint Laszlo and Poliska, Szilard and
Ruhl, Ralph and Nagy, Laszlo},
title = {Activation of retinoic acid receptor signaling coordinates lineage
commitment of spontaneously differentiating mouse embryonic stem
cells in embryoid bodies},
journal = {FEBS Lett},
year = {2010},
volume = {584},
pages = {3123--3130},
number = {14},
month = jul,
abstract = {Retinoid signaling has been implicated in embryonic stem cell differentiation.
Here we present a systematic analysis of gene expression changes
in mouse embryonic stem cells (mESCs), during their spontaneous differentiation
into embryoid bodies and the effect of all-trans retinoic acid (ATRA)
on this process. We show that retinoic acid is present in the serum
and is sufficient to activate retinoid signaling at a basal level
in undifferentiated mESCs. This signal disappears during embryoid
body formation. However exogenously added ATRA resets the spontaneous
differentiation programs in embryoid bodies and initiates a distinct
genetic program. These data suggest that retinoid signaling not only
promotes a particular pathway but also acts as a context dependent
general coordinator of the differentiation states in embryonic stem
cells.},
issn = {0014-5793},
keywords = {Retinoid signaling, Retinoic acid receptor, All-trans retinoic acid,
Mouse embryonic stem cell, Embryoid body, Transcription},
publisher = {Elsevier Science B.V.},
refid = {S0014-5793(10)00456-4},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0014579310004564?showall=true}
}
@ARTICLE{Simi2010,
author = {Simi, Lisa and Malentacchi, Francesca and Luciani, Paola and Gelmini,
Stefania and Deledda, Cristiana and Arvia, Rosaria and Mannelli,
Massimo and Peri, Alessandro and Orlando, Claudio},
title = {Seladin-1 expression is regulated by promoter methylation in adrenal
cancer},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {201},
number = {1},
abstract = {BACKGROUND:Seladin-1 overexpression exerts a protective mechanism
against apoptosis. Seladin-1 mRNA is variably expressed in normal
human tissues. Adrenal glands show the highest levels of seladin-1
expression, which are significantly reduced in adrenal carcinomas
(ACC). Since up to now seladin-1 mutations were not described, we
investigated whether promoter methylation could account for the down-regulation
of seladin-1 expression in ACC.METHODS:A methylation sensitive site
was identified in the seladin-1 gene. We treated DNA extracted from
two ACC cell lines (H295R and SW13) with the demethylating agent
5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence
of an epigenetic regulation also 'in vivo', seladin-1 methylation
and its mRNA expression were measured in 9 ACC and in 5 normal adrenal
glands.RESULTS:The treatment of cell lines with 5-Aza induced a significant
increase of seladin-1 mRNA expression in H295R (fold increase, F.I.
= 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation
density of seladin-1 promoter was higher (2682 ± 686) than in normal
adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in
ACC (1452 ± 196) was significantly lower than in normal adrenal glands
(3614 ± 949; p = 0.01).CONCLUSION:On this basis, methylation could
be involved in the altered pattern of seladin-1 gene expression in
ACC.},
doi = {10.1186/1471-2407-10-201},
issn = {1471-2407},
pubmedid = {20465827},
url = {http://www.biomedcentral.com/1471-2407/10/201}
}
@ARTICLE{Simi2006,
author = {Simi, Lisa and Venturini, Giulia and Malentacchi, Francesca and Gelmini,
Stefania and Andreani, Matteo and Janni, Alberto and Pastorekova,
Silvia and Supuran, Claudiu T. and Pazzagli, Mario and Orlando, Claudio},
title = {Quantitative analysis of carbonic anhydrase IX mRNA in human non-small
cell lung cancer},
journal = {Lung Cancer},
year = {2006},
volume = {52},
pages = {59--66},
number = {1},
month = apr,
abstract = {Summary Hypoxia is associated with malignant progression and poor
outcome in human cancers. The effects of hypoxia are mediated by
a series of genomic changes that enable tumor cells to survive or
escape their oxygen deficient environment. Recent studies indicated
that carbonic anhydrase IX (CA IX) is an intrinsic marker of hypoxia.
In the present study we investigated with quantitative RT-PCR the
expression of CA IX mRNA in 93 non-small cell lung carcinomas (NSCLC)
and in their paired not affected tissues. CA IX mRNA was expressed
in 100% NSCLC and in 76% of paired not affected tissues, even if
tumoral CA IX expression was found constantly higher (p < 0.02) than
that found in normal tissues. The increase of CA IX mRNA expression
in cancer tissues was significantly correlated to the increase of
corresponding protein, as determined with conventional immunoblotting
(p = 0.027). In addition the expression of CA IX mRNA in NSCLC samples
was significantly correlated to VEGF (p = 0.002) and MMP-9 (p = 0.002)
mRNAs. Whereas CA IX mRNA expression was not associated to any clinical-pathological
parameters in our patients, global survival analysis of cancer-related
death revealed that high expression of CA IX mRNA predicted unfavorable
outcome (p = 0.001) and shorter disease free survival interval (p = 0.004).
A multivariate analysis showed that CA IX expression was the strongest
prognostic parameter (p = 0.000) in comparison to other conventional
predictive markers. In addition, differences emerged on the basis
of clinical-pathological parameters: in fact separate Kaplan-Meyer
analyses of patients indicated that whereas high levels of CA IX
mRNA expression were not predictive of worse prognosis in early NSCLC
(G1, T1, Stage 1 and pN- patients), this parameter appeared highly
significant in advanced NSCLC (G2-G3, T2-T3, Stage 2-3 and pN+ patients).
Finally we demonstrated that CA IX expression was not able to discriminate
different survival probability in adenocarcinomas, whereas the same
parameter was highly predictive in squamous (p = 0.03) and adenosquamous
cell carcinomas (p = 0.001).},
issn = {0169-5002},
keywords = {Hypoxia, Real time RT-PCR, TaqMan probes, Immunoblotting},
url = {http://www.sciencedirect.com/science/article/B6T9C-4JCCJFG-1/2/57af6ebcd8ab4d1893b80a6e347a6e23}
}
@ARTICLE{Simion2010,
author = {Simion, Alexandru and Laudadio, Ilaria and Prévot, Pierre-Paul and
Raynaud, Peggy and Lemaigre, Frédéric P. and Jacquemin, Patrick},
title = {MiR-495 and miR-218 regulate the expression of the Onecut transcription
factors HNF-6 and OC-2},
journal = {Biochemical and Biophysical Research Communications},
year = {2010},
volume = {391},
pages = {293--298},
number = {1},
month = jan,
abstract = {MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate
gene expression mainly by binding to the 3'UTR of their target mRNAs.
Recent data revealed that microRNAs have an important role in pancreas
and liver development and physiology. Using cloning and microarray
profiling approaches, we show that a unique repertoire of microRNAs
is expressed at the onset of liver and pancreas organogenesis, and
in pancreas and liver at key stages of cell fate determination. Among
the microRNAs that are expressed at these stages, miR-495 and miR-218
were predicted to, respectively, target the Onecut (OC) transcription
factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important
regulators of liver and pancreas development. MiR-495 and miR-218
are dynamically expressed in developing liver and pancreas, and by
transient transfection, we show that they target HNF-6 and OC-2 3'UTRs.
Moreover, when overexpressed in cultured cells, miR-495 and miR-218
decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results
indicate that the expression of regulators of liver and pancreas
development is modulated by microRNAs. They also suggest a developmental
role for miR-495 and miR-218.},
issn = {0006-291X},
keywords = {Liver, Pancreas, miRNA, HNF-6, OC-2, Development, Mouse development,
Transcription factor},
url = {http://www.sciencedirect.com/science/article/B6WBK-4XNW435-7/2/221f47b88eb1eaa3c0a3bad249601e0d}
}
@ARTICLE{Simionescu2005,
author = {Simionescu, Agneta and Philips, Katherine and Vyavahare, Narendra},
title = {Elastin-derived peptides and TGF-[beta]1 induce osteogenic responses
in smooth muscle cells},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {334},
pages = {524--532},
number = {2},
month = aug,
abstract = {Elastin degradation associated with matrix metalloproteinase activity
is a cell-mediated process, observed in almost all types of vascular
calcification. In this study, we tested the hypothesis that elastin-derived
peptides induce an osteogenic response in vascular smooth muscle
cells (SMCs) in vitro. Using RT-PCR and specific protein assays,
we demonstrated that rat aortic SMCs incubated with elastin peptides
exhibited an increased expression of the 67 kDa elastin laminin receptor
(ELR) and matrix metalloproteinase-2 and typical bone proteins, such
as core binding factor [alpha]-1, osteocalcin, and alkaline phosphatase.
The osteogenic gene expression in SMCs was further enhanced by the
addition of TGF-[beta]1 along with the elastin peptides, in the absence
of any other mineralizing agent. Conversely, lactose (an ELR antagonist)
down-regulated expression of most investigated proteins. In conclusion,
elastin-derived peptides and TGF-[beta]1 up-regulate the expression
of typical bone proteins in cultured rat aortic SMCs, possibly via
the ELR signaling.},
issn = {0006-291X},
keywords = {Elastin peptides, TGF-[beta]1, Osteogenic phenotype, Cbfa-1, Alkaline
phosphatase, Vascular calcification},
url = {http://www.sciencedirect.com/science/article/B6WBK-4GHR94M-7/2/97d63a3148593a653e0d1bc750215c13}
}
@ARTICLE{Simionescu2007,
author = {Simionescu, Agneta and Simionescu, Dan T. and Vyavahare, Narendra
R.},
title = {Osteogenic Responses in Fibroblasts Activated by Elastin Degradation
Products and Transforming Growth Factor-{beta}1: Role of Myofibroblasts
in Vascular Calcification},
journal = {Am. J. Pathol.},
year = {2007},
volume = {171},
pages = {116--123},
number = {1},
month = jul,
abstract = {Our objective was to establish the role of fibroblasts in medial vascular
calcification, a pathological process known to be associated with
elastin degradation and remodeling. Rat dermal fibroblasts were treated
in vitro with elastin degradation products and transforming growth
factor (TGF)-{beta}1, factors usually present in deteriorated matrix
environments. Cellular changes were monitored at the gene and protein
level by reverse transcriptase-polymerase chain reaction, enzyme-linked
immunosorbent assay, immunofluorescence, and von Kossa staining for
calcium deposits. By 21 days, multicellular calcified nodules were
formed in the presence of elastin degradation products and TGF-{beta}1
separately and to a significantly greater extent when used together.
Before mineralization, cells expressed {alpha}-smooth muscle actin
and large amounts of collagen type I and matrix metalloproteinase-2,
characteristic features of myofibroblasts, key elements in tissue
remodeling and repair. Stimulated cells expressed increased levels
of core-binding factor {alpha}1, osteocalcin, alkaline phosphatase,
and osteoprotegerin, representative bone-regulating proteins. For
most proteins analyzed, TGF-{beta}1 synergistically amplified responses
of fibroblasts to elastin degradation products. In conclusion, elastin
degradation products and TGF-{beta}1 promote myofibroblastic and
osteogenic differentiation in fibroblasts. These results support
the idea that elastin-related calcification involves dynamic remodeling
events and suggest the possibility of a defective tissue repair process.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/171/1/116}
}
@ARTICLE{Simister2011,
author = {Simister, Rachel L. and Schmitt, Susanne and Taylor, Michael W.},
title = {Evaluating methods for the preservation and extraction of DNA and
RNA for analysis of microbial communities in marine sponges},
journal = {Journal of Experimental Marine Biology and Ecology},
year = {2011},
volume = {397},
pages = {38--43},
number = {1},
month = jan,
abstract = {Preservation and extraction of high quality DNA and RNA from biological
samples are becoming increasingly important for genomics, transcriptomics
and microbial community analyses. Of major recent interest, due to
their ecological and biotechnological importance, are the communities
of microorganisms associated with marine sponges. In this study,
we systematically evaluated protocols for the preservation (RNAlater,
liquid nitrogen, lyophilized, frozen) and extraction (CTAB-based
DNA extraction, RNA isolation via TRIzol and two co-extraction methods)
of nucleic acids using samples of the New Zealand high-microbial-abundance
sponge Ancorina alata. The quantity and quality of nucleic acids
were assessed via spectrophotometry, agarose gel electrophoresis
and microcapillary electrophoresis. Although all protocols resulted
in sufficiently high DNA and/or RNA quantity and quality for downstream
applications, there were significant differences in yield of nucleic
acids extracted. All RNA extraction methods maintained mRNA of sufficient
integrity to amplify the prokaryotic glutamine synthetase gene. Denaturing
gradient gel electrophoresis (DGGE) analysis of community 16S rRNA
gene- and 16S rRNA-derived fragments revealed several unique bands
in the rRNA-derived profiles. However, there were no major changes
attributable to either preservation or extraction method. Optimized
methods were successfully tested on three other New Zealand sponges.
Our results suggest that whilst choice of preservation and extraction
method does influence the quantity of nucleic acids isolated from
marine sponges, all protocols performed favorably, therefore the
choice of protocol can be made based on practical considerations
including ease of use, time availability and cost.},
issn = {0022-0981},
keywords = {Bacteria, DNA, Extraction, Preservation, RNA, Sponge},
url = {http://www.sciencedirect.com/science/article/pii/S0022098110004521}
}
@ARTICLE{Simmen2005,
author = {Simmen, Rosalia C.M. and Eason, Renea R. and Till, S. Reneé and Chatman,
Jr., Leon and Velarde, Michael C. and Geng, Yan and Korourian, Sohelia
and Badger, Thomas M.},
title = {Inhibition of NMU-induced mammary tumorigenesis by dietary soy},
journal = {Cancer Letters},
year = {2005},
volume = {224},
pages = {45--52},
number = {1},
month = jun,
abstract = {We previously demonstrated that female Sprague-Dawley rats fed AIN-93G
diets containing soy protein isolate (SPI+) had lower DMBA-induced
mammary tumor incidence than those fed diets containing casein (CAS),
due partly to altered Phase I metabolism with soy. Here, we evaluated
the tumor protective effects of these same diets to the direct-acting
carcinogen N-methyl-nitrosourea (NMU). Tumor incidence was reduced
and tumor latency was enhanced, in NMU-administered female rats lifetime
exposed to SPI+, relative to the CAS group. Tumor multiplicity did
not differ with diet, while tumor grade tended to be more advanced
with SPI+. Normal mammary glands of CAS and SPI+ tumor-bearing rats
had comparable proliferative and apoptotic status. However, mammary
expression of HER-2/neu and progesterone receptor (PR) genes was
higher for SPI+ rats. Moreover, tumored SPI+ rats had lower serum
progesterone levels than those fed CAS, while serum estrogen did
not differ. Serum from tumored SPI+ rats had higher apoptotic activity
towards mammary epithelial MCF-7 cells, than CAS serum. Thus, dietary
soy protects against mammary tumorigenesis induced by a direct-acting
carcinogen and alters signaling pathways involving PR and HER-2/neu.},
issn = {0304-3835},
keywords = {Mammary carcinoma, NMU, Soy proteins, Apoptosis, Progesterone},
url = {http://www.sciencedirect.com/science/article/B6T54-4F1503D-5/2/737432d01a16e499d1d7d7b2b9f79284}
}
@ARTICLE{Simmen2004,
author = {Simmen, Rosalia C. M. and Eason, Renea R. and McQuown, Jennelle R.
and Linz, Amanda L. and Kang, Tae-Jung and Chatman, Leon, Jr. and
Till, S. Renee and Fujii-Kuriyama, Yoshiaki and Simmen, Frank A.
and Oh, S. Paul},
title = {Subfertility, Uterine Hypoplasia, and Partial Progesterone Resistance
in Mice Lacking the Kruppel-like Factor 9/Basic Transcription Element-binding
Protein-1 (Bteb1) Gene},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {29286--29294},
number = {28},
month = jul,
abstract = {Progesterone receptor (PR), a ligand-activated transcription factor,
is a key regulator of cellular proliferation and differentiation
in reproductive tissues. The transcriptional activity of PR is influenced
by co-regulatory proteins typically expressed in a tissue- and cell-specific
fashion. We previously demonstrated that basic transcription element-binding
protein-1 (BTEB1), a member of the Sp/Kruppel-like family of transcription
factors, functionally interacts with the two PR isoforms, PR-A and
PR-B, to mediate progestin sensitivity of target genes in endometrial
epithelial cells in vitro. Here we report that ablation of the Bteb1
gene in female mice results in uterine hypoplasia, reduced litter
size, and increased incidence of neonatal deaths in offspring. The
reduced litter size is solely a maternal genotype effect and results
from fewer numbers of implantation sites, rather than defects in
ovulation. In the early pregnant uterus, Bteb1 expression in stromal
cells temporally coincides with PR-A isoform-dependent decidual formation
at the time of implantation. Expression of two implantation-specific
genes, Hoxa10 and cyclin D3, was decreased in uteri of early pregnant
Bteb1-null mutants, whereas that of Bteb3, a related family member,
was increased, the latter possibly compensating for the loss of Bteb1.
Progesterone responsiveness of several uterine genes was altered
with Bteb1-null mutation. These results identify Bteb1 as a functionally
relevant PR-interacting protein and suggest its selective modulation
of cellular processes that are regulated by PR-A in the uterine stroma.},
url = {http://www.jbc.org/cgi/content/abstract/279/28/29286}
}
@ARTICLE{Simmonds2010,
author = {Simmonds, Charlene S and Karsenty, Gerard and Karaplis, Andrew C
and Kovacs, Christopher S},
title = {Parathyroid hormone regulates fetal-placental mineral homeostasis},
journal = {J Bone Miner Res},
year = {2010},
volume = {25},
pages = {594--605},
number = {3},
abstract = {Abstract Parathyroid hormone (PTH) plays an essential role in regulating
calcium and bone homeostasis in the adult, but whether PTH is required
at all for regulating fetal-placental mineral homeostasis and skeletal
development is uncertain. We hypothesized that despite its low circulating
levels during fetal life, PTH plays a critical role in regulating
these processes. To address this, we examined two different genetic
models of PTH deficiency. Pth null mice have enlarged parathyroids
that are incapable of making PTH, whereas Gcm2 null mice lack parathyroids
but have PTH that arises from the thymus. Pth nulls served as a model
of complete absence of PTH, whereas Gcm2 nulls were a model of severe
hypoparathyroidism. We determined that PTH contributes importantly
to fetal mineral homeostasis because in its absence a fetal hypoparathyroid
phenotype results with hypocalcemia, hypomagnesemia, hyperphosphatemia,
low amniotic fluid mineral content, and reduced skeletal mineral
content. We also determined that PTH is expressed in the placenta,
regulates the placental expression of genes involved in calcium and
other solute transfer, and may directly stimulate placental calcium
transfer. Although parathyroid hormone–related protein (PTHrP)
acts in concert with PTH to regulate fetal mineral homeostasis and
placental calcium transfer, unlike PTH, it does not upregulate in
response to fetal hypocalcemia. © 2010 American Society for Bone
and Mineral Research},
issn = {1523-4681},
keywords = {Fetus, Pth/pthrp, Bone mineralization, Ion Transport/placenta, Knockout,
Animal Models/rodent, Growth and Development},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1359/jbmr.090825}
}
@ARTICLE{Simms2008,
author = {Simms, Amy N. and Mobley, Harry L. T.},
title = {PapX, a P Fimbrial Operon-Encoded Inhibitor of Motility in Uropathogenic
Escherichia coli},
journal = {Infect. Immun.},
year = {2008},
volume = {76},
pages = {4833--4841},
number = {11},
month = nov,
abstract = {Motility and adherence are two integral aspects of bacterial pathogenesis.
Adherence, often mediated by fimbriae, permits bacteria to attach
to host cells and establish infection, whereas flagellum-driven motility
allows bacteria to disseminate to sites more advantageous for colonization.
Both fimbriae and flagella have been proven important for virulence
of uropathogenic Escherichia coli (UPEC). Reciprocal regulation is
one mechanism by which bacteria may reconcile the contradictory actions
of adherence and motility. PapX, a P fimbrial gene product of UPEC
strain CFT073, is a functional homolog of MrpJ of Proteus mirabilis;
ectopic expression of papX in P. mirabilis reduces motility. To define
the connection between P fimbria expression and motility in UPEC,
the role of papX in the regulation of motility of strain CFT073 was
examined. Overexpression of papX decreased motility of CFT073, which
correlated with both a significant reduction in flagellin protein
synthesized and flagella assembled on the cell surface. Conversely,
an increase in motility and flagellin production was seen in an isogenic
papX deletion mutant of CFT073. Microarray and quantitative reverse
transcription-PCR analysis indicated that repression of motility
of CFT073 by PapX appears to occur at the transcriptional level;
expression of many motility-associated genes, including flhDC, the
master regulator of motility, is decreased when papX is overexpressed.
Transcription of motility genes is increased in the papX mutant compared
to wild type. Electrophoretic mobility gel shift analysis revealed
that PapX binds to the flhD promoter. We conclude that synthesis
of P fimbriae regulates flagellum synthesis to repress motility via
PapX.},
url = {http://iai.asm.org/cgi/content/abstract/76/11/4833}
}
@ARTICLE{Simms2008a,
author = {Simms, L A and Doecke, J D and Walsh, M D and Huang, N and Fowler,
E V and Radford-Smith, G L},
title = {Reduced {alpha}-defensin expression is associated with inflammation
and not NOD2 mutation status in ileal Crohn's disease},
journal = {Gut},
year = {2008},
volume = {57},
pages = {903--910},
number = {7},
month = jul,
abstract = {Background and aimsReduced ileal Paneth cell {alpha}-defensin expression
has been reported to be associated with Crohn's disease, especially
in patients carrying NOD2 mutations. The aim of this study was to
independently assess whether NOD2, {alpha}-defensins and Crohn's
disease are linked. MethodsUsing quantitative real-time polymerase
chain reaction (RT-PCR), we measured the mRNA expression levels of
key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A),
inflammatory cytokines [interkelukin 6 (IL6) and IL8], and a marker
of epithelial cell content, villin (VIL1) in 106 samples from both
affected ileum (inflamed Crohn's disease cases, n = 44) and unaffected
ileum (non-inflamed; Crohn's disease cases, n = 51 and controls,
n = 11). Anti-human defensin 5 (HD-5) and haematoxylin/eosin immunohistochemical
staining was performed on parallel sections from NOD2 wild-type and
NOD2 mutant ileal Crohn's disease tissue. ResultsIn Crohn's disease
patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold
lower, respectively, in histologically confirmed inflamed ileal mucosa
after adjustment for confounders (DEFA5, p<0.001; DEFA6, p = 0.001).
In contrast to previous studies, we found no significant association
between {alpha}-defensin expression and NOD2 genotype. HD-5 protein
data supports these RNA findings. The reduction in HD-5 protein expression
appears due to surface epithelial cell loss and reduced Paneth cell
numbers as a consequence of tissue damage. ConclusionsReduction in
{alpha}-defensin expression is independent of NOD2 status and is
due to loss of surface epithelium as a consequence of inflammatory
changes rather than being the inciting event prior to inflammation
in ileal Crohn's disease.},
url = {http://gut.bmj.com/cgi/content/abstract/57/7/903}
}
@ARTICLE{Simon2008,
author = {Simon, Dagmar and Hösli, Susanne and Kostylina, Ganna and Yawalkar,
Nikhil and Simon, Hans-Uwe},
title = {Anti-CD20 (rituximab) treatment improves atopic eczema},
journal = {Journal of Allergy and Clinical Immunology},
year = {2008},
volume = {121},
pages = {122--128},
number = {1},
month = jan,
abstract = {Background Atopic eczema (AE) is a chronic inflammatory skin disorder
characterized by eczematous skin lesions, pruritus, and typical histopathologic
features.Objective We asked whether depletion of B cells by monoclonal
anti-CD20 antibody therapy (rituximab) would improve severe AE.Methods
Six patients (4 women and 2 men) with severe AE received 2 intravenous
applications of rituximab, each 1000 mg, 2 weeks apart. To evaluate
the efficacy of rituximab, we monitored clinical parameters (eczema
area and severity index, pruritus), total and allergen-specific IgE
levels, skin histology, and inflammatory cells and cytokine expression
in the skin and peripheral blood before and after therapy (ClinicalTrials.gov
Identifier: NCT00267826).Results All patients showed an improvement
of their skin symptoms within 4 to 8 weeks. The eczema area and severity
index significantly decreased (before therapy, 29.4 ± 4.3; week 8,
8.4 ± 3.6; P < .001). Histologic alterations such as spongiosis,
acanthosis, and dermal infiltrate, including T and B cell numbers,
also dramatically improved. However, whereas blood B cells were below
detectable levels as a consequence of rituximab administration, skin
B cells were reduced by approximately 50% only. Expression of IL-5
and IL-13 was reduced after therapy. Moreover, whereas allergen-specific
IgE levels were not altered, we observed a slight reduction in total
IgE concentrations in blood.Conclusions B cells play a major role
in AE pathogenesis. Treatment with an anti-CD20 antibody leads to
an impressive improvement of AE in patients with severe disease.},
issn = {0091-6749},
keywords = {Atopic dermatitis, B cells, biologics, cytokines, inflammation, rituximab,
T cells},
url = {http://www.sciencedirect.com/science/article/B6WH4-4RKSKVY-R/2/5054f815c29724e37fe1d27afb6be31e}
}
@ARTICLE{Simon2011,
author = {Dana F. Simon and Thomas A. Davis and Mary-Lou Tercier-Waeber and
Roxane England and Kevin J. Wilkinson},
title = {In situ evaluation of cadmium biomarkers in green algae},
journal = {Environmental Pollution},
year = {2011},
volume = {159},
pages = {2630 - 2636},
number = {10},
note = {Nitrogen Deposition, Critical Loads and Biodiversity},
abstract = {In situ measurements provide data that are the highly representative
of the natural environment. In this paper, laboratory-determined
biomarkers of Cd stress that were previously identified for the green
alga Chlamydomonas reinhardtii, were tested in two French rivers:
a contaminated site on the Riou Mort River and an “uncontaminated�
reference site on the Lot River. Transcript abundance levels were
determined by real time qPCR for biomarkers thought to be Cd sensitive.
Transcript levels were significantly higher (>5 fold) for organisms
exposed to the contaminated site as compared to those exposed at
the uncontaminated site. Biomarker mRNA levels were best correlated
to free Cd (Cd2+) rather than intracellular Cd, suggesting that they
may be useful indicators of in situ stress. The paper shows that
biomarker expression levels increased with time, were sensitive to
metal levels and metal speciation and were higher in the “contaminated�
as opposed to the “reference� site.},
doi = {10.1016/j.envpol.2011.05.028},
issn = {0269-7491},
keywords = {Algae},
url = {http://www.sciencedirect.com/science/article/pii/S0269749111003150}
}
@ARTICLE{Simon2008a,
author = {Simon, Dana F. and Descombes, Patrick and Zerges, William and Wilkinson,
Kevin J.},
title = {Global expression profiling of Chlamydomonas reinhardtii exposed
to trace levels of free cadmium},
journal = {Environmental Toxicology and Chemistry},
year = {2008},
volume = {27},
pages = {1668--1675},
number = {8},
abstract = {Abstract 10.1897/07-649.1.abs In the natural environment, cadmium
is often found as a trace contaminant. Due to the complexity of Cd
speciation and the heterogeneity of natural systems and processes,
it is often difficult to determine clear relationships between analytical
measurements of Cd and its induced biological response. Measurements
of gene induction can be used to identify molecular mechanisms underlying
toxicity and to quantify sublethal responses to trace contaminants.
In the present paper, genes that could be involved in the tolerance
of Cd to green algae were examined using two global transcriptome
profiling strategies. Microarray and differential display techniques
were used for a global transcriptome analysis of Chlamydomonas reinhardtii
exposed to micromolar and lower Cd2+ concentrations for a short period
(2 h). Real-time quantitative polymerase chain reaction analysis
confirmed that a small set of 10 genes was differentially expressed
in response to trace Cd2+ exposures ranging from 7.8 nM to 9.0 μM.
Since induction was only observed for a few genes, none of which
are known to function in a general stress response, it was likely
the result of relevant responses to Cd exposure. The identified genes
are discussed with respect to their possible involvement in Cd tolerance
and to their future use as biomarkers for monitoring Cd bioavailability
in natural soils and waters.},
issn = {1552-8618},
keywords = {Cadmium, Microarrays, Gene expression, Differential display, Speciation},
publisher = {Wiley Periodicals, Inc.},
url = {http://dx.doi.org/10.1897/07-649.1}
}
@ARTICLE{Simon2009,
author = {Simon, Kirk and Mukundan, Anju and Dewundara, Samantha and Van Remmen,
Holly and Dombkowski, Alan A. and Cabelof, Diane C.},
title = {Transcriptional profiling of the age-related response to genotoxic
stress points to differential DNA damage response with age},
journal = {Mechanisms of Ageing and Development},
year = {2009},
volume = {130},
pages = {637--647},
number = {9},
month = sep,
abstract = {The p53 DNA damage response attenuated with age and we have evaluated
downstream factors in the DNA damage response. In old animals p21
protein accumulates in the whole cell fraction but significantly
declines in the nucleus, which may alter cell cycle and apoptotic
programs in response to DNA damage. We evaluated the transcriptional
response to DNA damage in young and old and find 2692 genes are differentially
regulated in old compared to young in response to oxidative stress
(p < 0.005). As anticipated, the transcriptional profile of young
mice is consistent with DNA damage induced cell cycle arrest while
the profile of old mice is consistent with cell cycle progression
in the presence of DNA damage, suggesting the potential for catastrophic
accumulation of DNA damage at the replication fork. Unique sets of
DNA repair genes are induced in response to damage in old and young,
suggesting the types of damage accumulating differs between young
and old. The DNA repair genes upregulated in old animals point to
accumulation of replication-dependent DNA double strand breaks (DSB).
Expression data is consistent with loss of apoptosis following DNA
damage in old animals. These data suggest DNA damage responses differ
greatly in young and old animals.},
issn = {0047-6374},
keywords = {DNA repair, p53, Aging, DNA damage response, Cell cycle},
url = {http://www.sciencedirect.com/science/article/B6T31-4X01P7X-1/2/4204ab3a049a5b880b586e79f3d2b8a9}
}
@ARTICLE{Simon2007,
author = {Simon, W. A. and Herrmann, M. and Klein, T. and Shin, J. M. and Huber,
R. and Senn-Bilfinger, J. and Postius, S.},
title = {Soraprazan: Setting New Standards in Inhibition of Gastric Acid Secretion},
journal = {J. Pharmacol. Exp. Ther.},
year = {2007},
volume = {321},
pages = {866--874},
number = {3},
month = jun,
abstract = {After treatment of millions of patients suffering from gastroesophageal
reflux disease (GERD) and other acid-related ailments with proton
pump inhibitors, there are still unmet medical needs such as rapid
and reliable pain relief, especially for nocturnal acid breakthrough.
In this work, we introduce and characterize the biochemistry and
pharmacology of the potassium-competitive acid blocker (P-CAB) soraprazan,
a novel, reversible, and fast-acting inhibitor of gastric H,K-ATPase.
Inhibitory and binding properties of soraprazan were analyzed together
with its mode of action, its selectivity, and its in vivo potency.
This P-CAB has an IC50 of 0.1 {micro}M if measured with ion leaky
vesicles and of 0.19 {micro}M in isolated gastric glands. With a
Ki of 6.4 nM, a Kd of 26.4 nM, and a Bmax of 2.89 nmol/mg, this compound
is a highly potent and reversible inhibitor of the H,K-ATPase. Soraprazan
shows immediate inhibition of acid secretion in various in vitro
models and in vivo and was found to be more than 2000-fold selective
for H,K-ATPase over Na,K- and Ca-ATPases. Soraprazan is superior
to esomeprazole in terms of onset of action and the extent and duration
of pH elevation in vivo in the dog. Rapid and consistent inhibition
of acid secretion by soraprazan renders the P-CABs a promising group
of compounds for therapy of GERD.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/321/3/866}
}
@ARTICLE{Simoncic2011,
author = {Simoncic, Matjaž and Režen, Tadeja and Juvan, Peter and Rozman, Damjana
and Fazarinc, Gregor and Fievet, Catherine and Staels, Bart and Horvat,
Simon},
title = {Obesity resistant mechanisms in the Lean polygenic mouse model as
indicated by liver transcriptome and expression of selected genes
in skeletal muscle},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {96},
number = {1},
abstract = {BACKGROUND:Divergently selected Lean and Fat mouse lines represent
unique models for a polygenic form of resistance and susceptibility
to obesity development. Previous research on these lines focused
mainly on obesity-susceptible factors in the Fat line. This study
aimed to examine the molecular basis of obesity-resistant mechanisms
in the Lean line by analyzing various fat depots and organs, the
liver transcriptome of selected metabolic pathways, plasma and lipid
homeostasis and expression of selected skeletal muscle genes.RESULTS:Expression
profiling using our custom Steroltalk v2 microarray demonstrated
that Lean mice exhibit a higher hepatic expression of cholesterol
biosynthesis genes compared to the Fat line, although this was not
reflected in elevation of total plasma or liver cholesterol. However,
FPLC analysis showed that protective HDL cholesterol was elevated
in Lean mice. A significant difference between the strains was also
found in bile acid metabolism. Lean mice had a higher expression
of Cyp8b1, a regulatory enzyme of bile acid synthesis, and the Abcb11
bile acid transporter gene responsible for export of acids to the
bile. Additionally, a higher content of blood circulating bile acids
was observed in Lean mice. Elevated HDL and upregulation of some
bile acids synthesis and transport genes suggests enhanced reverse
cholesterol transport in the Lean line - the flux of cholesterol
out of the body is higher which is compensated by upregulation of
endogenous cholesterol biosynthesis. Increased skeletal muscle Il6
and Dio2 mRNA levels as well as increased activity of muscle succinic
acid dehydrogenase (SDH) in the Lean mice demonstrates for the first
time that changes in muscle energy metabolism play important role
in the Lean line phenotype determination and corroborate our previous
findings of increased physical activity and thermogenesis in this
line. Finally, differential expression of Abcb11 and Dio2 identifies
novel strong positional candidate genes as they map within the quantitative
trait loci (QTL) regions detected previously in crosses between the
Lean and Fat mice.CONCLUSION:We identified novel candidate molecular
targets and metabolic changes which can at least in part explain
resistance to obesity development in the Lean line. The major difference
between the Lean and Fat mice was in increased liver cholesterol
biosynthesis gene mRNA expression, bile acid metabolism and changes
in selected muscle genes' expression in the Lean line. The liver
Abcb11 and muscle Dio2 were identified as novel positional candidate
genes to explain part of the phenotypic difference between the Lean
and Fat lines.},
doi = {10.1186/1471-2164-12-96},
issn = {1471-2164},
pubmedid = {21291556},
url = {http://www.biomedcentral.com/1471-2164/12/96}
}
@ARTICLE{Simonet2004,
author = {Simonet, Gert and Claeys, Ilse and Breugelmans, Bert and Van Soest,
Sofie and De Loof, Arnold and Vanden Broeck, Jozef},
title = {Transcript profiling of pacifastin-like peptide precursors in crowd-
and isolated-reared desert locusts},
journal = {Biochemical and Biophysical Research Communications},
year = {2004},
volume = {317},
pages = {565--569},
number = {2},
month = apr,
issn = {0006-291X},
keywords = {Protease inhibitor, Peptide family, Real-time PCR, Gene expression,
Schistocerca gregaria, Phase transition, Solitary, Gregarious},
url = {http://www.sciencedirect.com/science/article/B6WBK-4C0V4YB-B/2/5f404c9784530631b48c7887a7370c50}
}
@ARTICLE{Simonet2004a,
author = {Simonet, Gert and Claeys, Ilse and Van Soest, Sofie and Breugelmans,
Bert and Franssens, Vanessa and De Loof, Arnold and Vanden Broeck,
Jozef},
title = {Molecular identification of SGPP-5, a novel pacifastin-like peptide
precursor in the desert locust},
journal = {Peptides},
year = {2004},
volume = {25},
pages = {941--950},
number = {6},
month = jun,
issn = {0196-9781},
keywords = {Protease inhibitor, Peptide family, Real-time PCR, Gene expression,
Schistocerca gregaria, Cuticle, Entomopathogenic fungus},
url = {http://www.sciencedirect.com/science/article/B6T0M-4C7DH2B-2/2/dc1678f3f0d7bc8ca1e212b0fa7384ac}
}
@ARTICLE{Simonet2011,
author = {Simonet, Thomas and Zaragosi, Laure-Emmanuelle and Philippe, Claude
and Lebrigand, Kevin and Schouteden, Clementine and Augereau, Adeline
and Bauwens, Serge and Ye, Jing and Santagostino, Marco and Giulotto,
Elena and Magdinier, Frederique and Horard, Beatrice and Barbry,
Pascal and Waldmann, Rainer and Gilson, Eric},
title = {The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial
telomeric sequences and satellite repeats},
journal = {Cell Res},
year = {2011},
pages = {--},
month = mar,
issn = {1748-7838},
publisher = {Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences},
url = {http://dx.doi.org/10.1038/cr.2011.40}
}
@ARTICLE{Simonin2007,
author = {Simonin, Yannick and Perrin, Florence E. and Kato, Ann C.},
title = {Axonal involvement in the Wlds neuroprotective effect: analysis of
pure motoneurons in a mouse model protected from motor neuron disease
at a pre-symptomatic age},
journal = {Journal of Neurochemistry},
year = {2007},
volume = {101},
pages = {530--542},
number = {2},
abstract = {Abstract The identification of the Wlds gene that delays axonal degeneration
in several models of neurodegenerative disease provides an interesting
tool to study mechanisms of axonal loss. We showed that crossing
a mouse mutant with a motoneuron disease (pmn for progressive motor
neuronopathy) with mice that express the Wlds gene delayed axonal
loss, increased the life span, partially rescued axonal transport
deficit and prolonged the survival of the motoneuron cell bodies.
To determine factors involved in the neuroprotective effect of Wlds,
we combined laser capture microdissection and microarray analysis
to identify genes that are differentially regulated at a pre-symptomatic
age in motoneuron cell bodies in pmn/pmn,Wlds/Wlds mice as compared
with pmn/pmn mice. Only 56 genes were de-regulated; none of the ‘classical’
genes implicated in apoptosis were de-regulated. Interestingly, a
large proportion of these genes are related to axonal function and
to retrograde and anterograde transport (i.e. members of the dynactin
complex and kinesin family). These results were confirmed by real-time
PCR, in situ hybridization and at protein level in sciatic nerves.
Thus, genes related to axonal function and in particular to axonal
transport may be involved at an early stage in the neuroprotective
property of the Wlds gene and confirm the importance of axonal involvement
in this model of motor neuron disease.},
issn = {1471-4159},
keywords = {axonal transport, laser capture microdissection, microarrays, motoneurons,
progressive motor neuronopathy mice, Wlds},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2006.04366.x}
}
@ARTICLE{Simonsen2010,
author = {Simonsen, Michelle L. and Alessio, Helaine M. and White, Peter and
Newsom, David L. and Hagerman, Ann E.},
title = {Acute physical activity effects on cardiac gene expression},
journal = {Exp Physiol},
year = {2010},
volume = {95},
pages = {1071--1080},
number = {11},
month = nov,
abstract = {Regular bouts of physical activity may cause changes in gene expression
that accumulate over time and ultimately affect phenotypes, such
as body weight, blood lipid profile and tumour development. Furthermore,
acute activity may affect gene expression and phenotypes differently
depending on whether the individual is regularly inactive or active.
One-month-old male Sprague-Dawley rats (n = 72) were equally divided
into SED (standard laboratory cage, n = 24), PA (large activity box,
n = 24) and EX groups (exercise wheel inside standard cage, n = 24).
At 3 months of age, half the animals from each group were killed
at rest and the other half following 30 min of physical activity.
The RNA was extracted from cardiac tissue, and microarray analysis
was performed on 27,000 genes. Select gene results were validated
using quantitative PCR. No gene expression differences occurred when
comparing all 3-month-old groups at rest. A relatively small percentage
of genes (1.9%) were differentially expressed (P < 0.05) following
acute swimming activity in all groups, but only 37 unique and identifiable
genes reached or exceeded twofold differences in expression. The
genes Atf3, Fos, Apold1 and Pxdn were expressed differently among
SED, PA and EX following acute activity, with a clear separation
of the magnitude in gene expression with SED > PA > EX. Differences
in gene expression levels in young physically inactive and active
animals following acute activity have different regulatory roles
in gene networks that affect health-related phenotypes.},
url = {http://ep.physoc.org/cgi/content/abstract/95/11/1071}
}
@ARTICLE{Simpson2003,
author = {Simpson, D.A. and MacFarlane, S. and Stitt, A.W.},
title = {A Microarray Comparison of the Molecular Phenotypes of the RPE Cell
Lines ARPE-19 and D407},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2003},
volume = {44},
pages = {2291--},
number = {5},
month = may,
abstract = {Purpose: ARPE-19 and D407 are two commonly used retinal pigment epithelial
cell lines. Both exhibit, to varying degrees, features of the RPE
in vivo. The aim of this investigation is to analyze whether the
pattern of genes expressed by these cell lines matches the expected
molecular phenotype of the RPE and to determine how differential
gene expression between the two cell lines correlates with their
observed in vitro phenotypes. Methods: The human ARPE-19 cell line
was obtained from the ATCC (Rockville, MD, USA) and maintained in
DMEM/F12 (Life Technologies) with 2% FCS. The human D407 RPE cell
line (Dr Richard Hunt) was maintained in DMEM (Life Technologies)
with 2% fetal calf serum (FCS). Total RNA was isolated with Tri-reagent
(Sigma), followed by DNase treatment and column purification (Qiagen).
RNA quality was assessed using a 2100 Bioanalyzer (Agilent). To measure
changes in gene expression RNA was extracted, reverse transcribed
and hybridized to a cDNA microarray containing 12,000 expressed human
sequences (Agilent human 1). Fluorescent labelling was performed
with a 3DNA Submicro Kit (Genisphere) and spot intensities measured
using ScanAlyze. Fold changes below 2.0 were disregarded. Quantitative
RT-PCR was performed using a LightCycler (Roche). Results: The ARPE-19
and D407 cells both display morphological features of the RPE in
vivo and were demonstrated to also express genes characteristic of
the RPE. In keeping with the contact-inhibited, differentiated nature
of ARPE-19 cultures a number of proteins implicated in cell attachment/matrix
interactions were among the most preferentially expressed relative
to D407. These included thrombospondin 1 precursor (~7 fold higher),
matrilin-2 precursor (~7 fold), Cadherin-related tumor suppressor
homolog precursor (~6 fold) and SPARC precursor (~4 fold). In contrast,
the most highly differentially expressed protein in D407 was the
S100P calcium binding protein (~13 fold) which has been associated
with transformed cells. Other genes associated with greater cell
turnover, such as histones and the MCM2 DNA replication licensing
factor, were also expressed at higher levels in D407. Conclusions:
Microarray analysis of different cell lines has revealed differential
gene expression which will contribute to our understanding of RPE
biology and role in pathology.},
url = {http://abstracts.iovs.org/cgi/content/abstract/44/5/2291}
}
@ARTICLE{Simpson2009,
author = {Simpson, Julie E. and Hosny, Ola and Wharton, Stephen B. and Heath,
Paul R. and Holden, Hazel and Fernando, Malee S. and Matthews, Fiona
and Forster, Gill and O'Brien, John T. and Barber, Robert and Kalaria,
Raj N. and Brayne, Carol and Shaw, Pamela J. and Lewis, Claire E.
and Ince, Paul G. and on behalf of the Medical Research Council Cognitive
Function and Ageing Study Neuropathology Group},
title = {Microarray RNA Expression Analysis of Cerebral White Matter Lesions
Reveals Changes in Multiple Functional Pathways},
journal = {Stroke},
year = {2009},
volume = {40},
pages = {369--375},
number = {2},
month = feb,
abstract = {Background and Purpose-- White matter lesions (WML) in brain aging
are linked to dementia and depression. Ischemia contributes to their
pathogenesis but other mechanisms may contribute. We used RNA microarray
analysis with functional pathway grouping as an unbiased approach
to investigate evidence for additional pathogenetic mechanisms. Methods--
WML were identified by MRI and pathology in brains donated to the
Medical Research Council Cognitive Function and Ageing Study Cognitive
Function and Aging Study. RNA was extracted to compare WML with nonlesional
white matter samples from cases with lesions (WM[L]), and from cases
with no lesions (WM[C]) using RNA microarray and pathway analysis.
Functional pathways were validated for selected genes by quantitative
real-time polymerase chain reaction and immunocytochemistry. Results--
We identified 8 major pathways in which multiple genes showed altered
RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis,
ion transport, cell structure, electron transport, metabolism) among
502 genes that were differentially expressed in WML compared to WM[C].
In WM[L], 409 genes were altered involving the same pathways. Genes
selected to validate this microarray data all showed the expected
changes in RNA levels and immunohistochemical expression of protein.
Conclusion-- WML represent areas with a complex molecular phenotype.
From this and previous evidence, WML may arise through tissue ischemia
but may also reflect the contribution of additional factors like
blood-brain barrier dysfunction. Differential expression of genes
in WM[L] compared to WM[C] indicate a "field effect" in the seemingly
normal surrounding white matter.},
url = {http://stroke.ahajournals.org/cgi/content/abstract/40/2/369}
}
@ARTICLE{Simpson2011,
author = {Julie E. Simpson and Paul G. Ince and Pamela J. Shaw and Paul R.
Heath and Rohini Raman and Claire J. Garwood and Catherine Gelsthorpe
and Lynne Baxter and Gillian Forster and Fiona E. Matthews and Carol
Brayne and Stephen B. Wharton},
title = {Microarray analysis of the astrocyte transcriptome in the aging brain:
relationship to Alzheimer's pathology and APOE genotype},
journal = {Neurobiology of Aging},
year = {2011},
volume = {32},
pages = {1795 - 1807},
number = {10},
abstract = {Astrocytes contribute to a variety of functions in the brain, including
homeostasis, synapse formation, plasticity, and metabolism. Astrocyte
dysfunction may disrupt their normal role, including neuronal support,
thereby contributing to neurodegenerative pathologies, including
Alzheimer's disease (AD). To understand the role of astrocytes in
the pathogenesis of age-related disorders, we isolated astrocytes
by laser capture microdissection, using glial fibrillary acidic protein
(GFAP) as a marker, and characterized the astrocyte transcriptome
at different Braak neurofibrillary tangle stages in postmortem temporal
cortex samples derived from the Medical Research Council Cognitive
Function and Ageing Study (MRC CFAS) cohort, using microarray analysis.
The largest number of significant, differentially expressed genes
were identified when the expression profile of astrocytes from isocortical
stages of neurofibrillary tangle pathology (Braak stages V–VI)
were compared with entorhinal stages (Braak stages I–II). Dysregulation
of genes associated with the actin cytoskeleton, proliferation, apoptosis,
and ubiquitin-mediated proteolysis occurred at low Braak stages,
while altered regulation of intracellular signaling pathways, including
insulin, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated
protein kinase (MAPK) pathways were primarily associated with high
levels of Alzheimer-type pathology, and occurred at lower Braak stages
in individuals with the APOEε4 allele. Our findings implicate astrocyte
dysfunction in the pathogenesis of neurodegenerative pathology in
the aging brain, and provide a basis for future candidate studies
based on specific pathways.},
doi = {10.1016/j.neurobiolaging.2011.04.013},
issn = {0197-4580},
keywords = {Astrocytes},
url = {http://www.sciencedirect.com/science/article/pii/S0197458011001783}
}
@ARTICLE{Sims2008,
author = {Sims, Andrew and Smethurst, Graeme and Hey, Yvonne and Okoniewski,
Michal and Pepper, Stuart and Howell, Anthony and Miller, Crispin
and Clarke, Robert},
title = {The removal of multiplicative, systematic bias allows integration
of breast cancer gene expression datasets – improving meta-analysis
and prediction of prognosis},
journal = {BMC Medical Genomics},
year = {2008},
volume = {1},
pages = {42},
number = {1},
abstract = {BACKGROUND:The number of gene expression studies in the public domain
is rapidly increasing, representing a highly valuable resource. However,
dataset-specific bias precludes meta-analysis at the raw transcript
level, even when the RNA is from comparable sources and has been
processed on the same microarray platform using similar protocols.
Here, we demonstrate, using Affymetrix data, that much of this bias
can be removed, allowing multiple datasets to be legitimately combined
for meaningful meta-analyses.RESULTS:A series of validation datasets
comparing breast cancer and normal breast cell lines (MCF7 and MCF10A)
were generated to examine the variability between datasets generated
using different amounts of starting RNA, alternative protocols, different
generations of Affymetrix GeneChip or scanning hardware. We demonstrate
that systematic, multiplicative biases are introduced at the RNA,
hybridization and image-capture stages of a microarray experiment.
Simple batch mean-centering was found to significantly reduce the
level of inter-experimental variation, allowing raw transcript levels
to be compared across datasets with confidence. By accounting for
dataset-specific bias, we were able to assemble the largest gene
expression dataset of primary breast tumours to-date (1107), from
six previously published studies. Using this meta-dataset, we demonstrate
that combining greater numbers of datasets or tumours leads to a
greater overlap in differentially expressed genes and more accurate
prognostic predictions. However, this is highly dependent upon the
composition of the datasets and patient characteristics.CONCLUSION:Multiplicative,
systematic biases are introduced at many stages of microarray experiments.
When these are reconciled, raw data can be directly integrated from
different gene expression datasets leading to new biological findings
with increased statistical power.},
doi = {10.1186/1755-8794-1-42},
issn = {1755-8794},
pubmedid = {18803878},
url = {http://www.biomedcentral.com/1755-8794/1/42}
}
@ARTICLE{Sims2011,
author = {Sims, David and Mendes-Pereira, Ana and Frankum, Jessica and Burgess,
Darren and Cerone, Maria-Antonietta and Lombardelli, Cristina and
Mitsopoulos, Costas and Hakas, Jarle and Murugaesu, Nirupa and Isacke,
Clare and Fenwick, Kerry and Assiotis, Ioannis and Kozarewa, Iwanka
and Zvelebil, Marketa and Ashworth, Alan and Lord, Christopher},
title = {High-throughput RNA interference screening using pooled shRNA libraries
and next generation sequencing},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R104},
number = {10},
abstract = {RNA interference (RNAi) screening is a state-of-the-art technology
that enables the dissection of biological processes and disease-related
phenotypes. The commercial availability of genome-wide, short hairpin
RNA (shRNA) libraries has fueled interest in this area but the generation
and analysis of these complex data remain a challenge. Here, we describe
complete experimental protocols and novel open source computational
methodologies, shALIGN and shRNAseq, that allow RNAi screens to be
rapidly deconvoluted using next generation sequencing. Our computational
pipeline offers efficient screen analysis and the flexibility and
scalability to quickly incorporate future developments in shRNA library
technology.},
doi = {10.1186/gb-2011-12-10-r104},
issn = {1465-6906},
pubmedid = {22018332},
url = {http://genomebiology.com/2011/12/10/R104}
}
@ARTICLE{Simunovic2009,
author = {Simunovic, Filip and Yi, Ming and Wang, Yulei and Macey, Laurel and
Brown, Lauren T. and Krichevsky, Anna M. and Andersen, Susan L. and
Stephens, Robert M. and Benes, Francine M. and Sonntag, Kai C.},
title = {Gene expression profiling of substantia nigra dopamine neurons: further
insights into Parkinson's disease pathology},
journal = {Brain},
year = {2009},
volume = {132},
pages = {1795--1809},
number = {7},
month = jul,
abstract = {Parkinson's disease is caused by a progressive loss of the midbrain
dopamine (DA) neurons in the substantia nigra pars compacta. Although
the main cause of Parkinson's disease remains unknown, there is increasing
evidence that it is a complex disorder caused by a combination of
genetic and environmental factors, which affect key signalling pathways
in substantia nigra DA neurons. Insights into pathogenesis of Parkinson's
disease stem from in vitro and in vivo models and from postmortem
analyses. Recent technological developments have added a new dimension
to this research by determining gene expression profiles using high
throughput microarray assays. However, many of the studies reported
to date were based on whole midbrain dissections, which included
cells other than DA neurons. Here, we have used laser microdissection
to isolate single DA neurons from the substantia nigra pars compacta
of controls and subjects with idiopathic Parkinson's disease matched
for age and postmortem interval followed by microarrays to analyse
gene expression profiling. Our data confirm a dysregulation of several
functional groups of genes involved in the Parkinson's disease pathogenesis.
In particular, we found prominent down-regulation of members of the
PARK gene family and dysregulation of multiple genes associated with
programmed cell death and survival. In addition, genes for neurotransmitter
and ion channel receptors were also deregulated, supporting the view
that alterations in electrical activity might influence DA neuron
function. Our data provide a molecular fingerprint identity' of late-stage
Parkinson's disease DA neurons that will advance our understanding
of the molecular pathology of this disease.},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/132/7/1795}
}
@ARTICLE{Simo2009,
author = {Simó, Rafael and García-Ramírez, Marta and Higuera, Mónica and Hernández,
Cristina},
title = {Apolipoprotein A1 Is Overexpressed in the Retina of Diabetic Patients},
journal = {American Journal of Ophthalmology},
year = {2009},
volume = {147},
pages = {319--325.e1},
number = {2},
month = feb,
abstract = {Purpose To compare apolipoprotein A1 (ApoA1) expression in the retina
from diabetic and nondiabetic donors.Design Case-control study.Methods
Diabetic postmortem eyes (n = 8) were compared with eyes (n = 8)
from nondiabetic donors matched by age. Messenger ribonucleic acid
(mRNA) of ApoA1 (quantitative reverse-transcriptase polymerase chain
reaction) was measured separately in the neuroretina and retinal
pigment epithelium (RPE). ApoA1 was assessed by immunofluorescence
(confocal laser microscopy) and Western blot analysis. The presence
of early diabetic retinal damage was evaluated by measuring the rate
of apoptosis and glial activation.Results ApoA1 mRNA levels and ApoA1
immunofluorescence obtained in RPEs and in neuroretinas from diabetic
donors were significantly higher than those obtained from nondiabetic
donors. ApoA1 was expressed in all retina layers and it was more
abundant in RPE than in the neuroretina in both diabetic and nondiabetic
donors. In addition, ApoA1 immunofluorescence was significantly higher
in all the layers of the neuroretina from diabetic patients. Densitometric
analysis of immunoblots showed higher ApoA1 in the retinas from diabetic
donors in comparison with nondiabetic donors, but the differences
were at significant levels only for the RPE.Conclusions ApoA1 overexpression
is an early event in the retina of diabetic patients and can be involved
in the physiopathology of diabetic retinopathy. In addition, RPE
is the main source of ApoA1 within the retina. These findings my
be relevant to aiming new treatment strategies toward reducing the
development of diabetic retinopathy.},
issn = {0002-9394},
url = {http://www.sciencedirect.com/science/article/B6VK5-4TMRK42-4/2/3e147a4401db3edefe5bfd1ee4e09805}
}
@ARTICLE{Simoes2008,
author = {Simões, Maria L. and Hockley, Sarah L. and Schwerdtle, Tanja and
Gamboa da Costa, Gonçalo and Schmeiser, Heinz H. and Phillips, David
H. and Arlt, Volker M.},
title = {Gene expression profiles modulated by the human carcinogen aristolochic
acid I in human cancer cells and their dependence on TP53},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {232},
pages = {86--98},
number = {1},
month = oct,
abstract = {Aristolochic acid (AA) is the causative agent of urothelial tumours
associated with aristolochic acid nephropathy. These tumours contain
TP53 mutations and over-express TP53. We compared transcriptional
and translational responses of two isogenic HCT116 cell lines, one
expressing TP53 (p53-WT) and the other with this gene knocked out
(p53-null), to treatment with aristolochic acid I (AAI) (50-100 [mu]M)
for 6-48 h. Modulation of 118 genes was observed in p53-WT cells
and 123 genes in p53-null cells. Some genes, including INSIG1, EGR1,
CAV1, LCN2 and CCNG1, were differentially expressed in the two cell
lines. CDKN1A was selectively up-regulated in p53-WT cells, leading
to accumulation of TP53 and CDKN1A. Apoptotic signalling, measured
by caspase-3 and -7 activity, was TP53-dependent. Both cell types
accumulated in S phase, suggesting that AAI-DNA adducts interfere
with DNA replication, independently of TP53 status. The oncogene
MYC, frequently over-expressed in urothelial tumours, was up-regulated
by AAI, whereas FOS was down-regulated. Observed modulation of genes
involved in endocytosis, e.g. RAB5A, may be relevant to the known
inhibition of receptor-mediated endocytosis, an early sign of AA-mediated
proximal tubule injury. AAI-DNA adduct formation was significantly
greater in p53-WT cells than in p53-null cells. Collectively, phenotypic
anchoring of the AAI-induced expression profiles to DNA adduct formation,
cell-cycle parameters, TP53 expression and apoptosis identified several
genes linked to these biological outcomes, some of which are TP53-dependent.
These results strengthen the importance of TP53 in AA-induced cancer,
and indicate that other alterations, e.g. to MYC oncogenic pathways,
may also contribute.},
issn = {0041-008X},
keywords = {Aristolochic acid, Urothelial cancer, TP53, Gene expression, Apoptosis,
Microarray},
url = {http://www.sciencedirect.com/science/article/B6WXH-4SV5V36-1/2/9cf95fdf6cec4e50626317102a0d24e5}
}
@ARTICLE{Sinchaikul2002,
author = {Sinchaikul, Supachok and Sookkheo, Boonyaras and Phutrakul, Suree
and Pan, Fu-Ming and Chen, Shui-Tein},
title = {Proteomic study of cold shock protein in Bacillus stearothermophilus
P1: Comparison of temperature downshifts},
journal = {Proteomics},
year = {2002},
volume = {2},
pages = {1316--1324},
number = {9},
abstract = {Abstract 10.1002/1615-9861(200209)2:9<1316::AID-PROT1316>3.3.CO;2-S
The thermophilic bacterium Bacillus stearothermophilus P1 is unique
in its ability to thrive in extreme environments such as high temperatures
or high pH conditions. The study of cold shock response is very interesting
and interpreted as a shock response to express the genes involved
in synthesis of specific proteins. This study investigated the study
of cold shock protein of B. stearothermophilus P1 when the cell culture
temperature shifted from 65°C to 37°C and 25°C. Cell growth at
37°C weakly increased in the previous 3 h and then slowly decreased.
In contrast, cell growth at 25°C was slowly decreased. The protein
contents after temperature downshifts were analyzed by proteomic
techniques using protein chip and two-dimensional (2-D) electrophoresis
that are highly effective and useful for protein separation and identification.
The different proteins after a temperature decrease from 65°C to
37°C and 25°C were expressed on 2-D gel patterns and the cold shock
protein was detected in the acidic area with the isoelectric point
and molecular mass approximately 4.5 and 7.3Â kDa, respectively.
The NH2-terminal sequence of a major cold shock protein from B. stearothermophilus
P1 was MQRGKVKWFNNEKGFGFIEVEGGSD, similar to other cold shock proteins
from Bacillus sp. up to 96% identity, but different from the other
bacteria with homology less than 80% identity.},
issn = {1615-9861},
keywords = {Bacillus stearothermophilus, Cold shock protein},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/1615-9861(200209)2:9<1316::AID-PROT1316>3.0.CO;2-0}
}
@ARTICLE{Sinchaikul2002a,
author = {Sinchaikul, Supachok and Sookkheo, Boonyaras and Topanuruk, Supachai
and Juan, Hsueh-Fen and Phutrakul, Suree and Chen, Shui-Tein},
title = {Bioinformatics, functional genomics, and proteomics study of Bacillus
sp.},
journal = {Journal of Chromatography B: Analytical Technologies in the Biomedical
and Life Sciences},
year = {2002},
volume = {771},
pages = {261--287},
number = {1-2},
month = may,
abstract = {The ability of bioinformatics to characterize genomic and proteomic
sequences from bacteria Bacillus sp. for prediction of genes and
proteins has been evaluated. Genomics coupling with proteomics, which
is relied on integration of the significant advances recently achieved
in two-dimensional (2-D) electrophoretic separation of proteins and
mass spectrometry (MS), are now important and high throughput techniques
for qualifying and analyzing gene and protein expression, discovering
new gene or protein products, and understanding of gene and protein
functions including post-genomic study. In addition, the bioinformatics
of Bacillus sp. is embraced into many databases that will facilitate
to rapidly search the information of Bacillus sp. in both genomics
and proteomics. It is also possible to highlight sites for post-translational
modifications based on the specific protein sequence motifs that
play important roles in the structure, activity and compartmentalization
of proteins. Moreover, the secreted proteins from Bacillus sp. are
interesting and widely used in many applications especially biomedical
applications that are the highly advantages for their potential therapeutic
values.},
issn = {1570-0232},
url = {http://www.sciencedirect.com/science/article/B6X0P-4569WX3-3/2/b30d2fffc9677a4306588c06cfb523e4}
}
@ARTICLE{Sindelka2008,
author = {Sindelka, Radek and Jonak, Jiri and Hands, Rebecca and Bustin, Stephen
A. and Kubista, Mikael},
title = {Intracellular expression profiles measured by real-time PCR tomography
in the Xenopus laevis oocyte},
journal = {Nucleic Acids Res.},
year = {2008},
volume = {36},
pages = {387--392},
number = {2},
month = feb,
abstract = {Real-time PCR tomography is a novel, quantitative method for measuring
localized RNA expression profiles within single cells. We demonstrate
its usefulness by dissecting an oocyte from Xenopus laevis into slices
along its animal-vegetal axis, extracting its RNA and measuring the
levels of 18 selected mRNAs by real-time RT-PCR. This identified
two classes of mRNA, one preferentially located towards the animal,
the other towards the vegetal pole. mRNAs within each group show
comparable intracellular gradients, suggesting they are produced
by similar mechanisms. The polarization is substantial, though not
extreme, with around 5% of vegetal gene mRNA molecules detected at
the animal pole, and around 50% of the molecules in the far most
vegetal section. Most animal pole mRNAs were found in the second
section from the animal pole and in the central section, which is
where the nucleus is located. mRNA expression profiles did not change
following in vitro fertilization and we conclude that the cortical
rotation that follows fertilization has no detectable effect on intracellular
mRNA gradients.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/36/2/387}
}
@ARTICLE{Singer2011,
author = {Singer, Katrin and Kastenberger, Michael and Gottfried, Eva and Hammerschmied,
Christine G. and Büttner, Maike and Aigner, Michael and Seliger,
Barbara and Walter, Bernhard and Schlösser, Hans and Hartmann, Arndt
and Andreesen, Reinhard and Mackensen, Andreas and Kreutz, Marina},
title = {Warburg phenotype in renal cell carcinoma: High expression of glucose-transporter
1 (GLUT-1) correlates with low CD8+ T-cell infiltration in the tumor},
journal = {International Journal of Cancer},
year = {2011},
volume = {128},
pages = {2085--2095},
number = {9},
abstract = {Abstract Many tumor cells are characterized by a dysregulated glucose
metabolism associated with increased glycolysis in the presence of
oxygen (“Warburg Effect�). Here, we analyzed for the first time
a possible link between glucose metabolism and immune cell infiltration
in renal cell carcinoma (RCC). RCC specimens revealed a highly significant
increase in the expression of lactate dehydrogenase A (LDHA) and
glucose-transporter 1 (GLUT-1) compared to the corresponding normal
kidney tissue on mRNA level. Accordingly, tumor cell lines of different
origin such as RCC, melanoma and hepatocellular carcinoma strongly
expressed LDHA and GLUT-1 compared to their nonmalignant counterparts.
In line with this finding, tumor cells secreted high amounts of lactate.
High expression of GLUT-1 and LDH5, a tetramer of 4 LDHA subunits,
was confirmed by tissue microarray analysis of 249 RCC specimens.
Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma
showed a constitutive, but heterogeneous expression of GLUT-1 and
LDH5, respectively. The number of CD3+, CD8+ and FOXP3+ T cells was
significantly elevated in RCC lesions compared to normal kidney epithelium,
but effector molecules such as granzyme B and perforin were decreased
in tumor infiltrating T cells. Of interest, further analysis revealed
an inverse correlation between GLUT-1 expression and the number of
CD8+ T cells in RCC lesions. Together, our data suggest that an accelerated
glucose metabolism in RCC tissue is associated with a low infiltration
of CD8+ effector T cells. Targeting the glucose metabolism may represent
an interesting tool to improve the efficacy of specific immunotherapeutic
approaches in RCC.},
doi = {10.1002/ijc.25543},
issn = {1097-0215},
keywords = {glucose-transporter 1, LDHA, TIL, renal cell carcinoma, Warburg, immune
escape},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25543}
}
@ARTICLE{Singer2009,
author = {Singer, Stephan and Malz, Mona and Herpel, Esther and Warth, Arne
and Bissinger, Michaela and Keith, Martina and Muley, Thomas and
Meister, Michael and Hoffmann, Hans and Penzel, Roland and Gdynia,
Georg and Ehemann, Volker and Schnabel, Philipp Albert and Kuner,
Ruprecht and Huber, Peter and Schirmacher, Peter and Breuhahn, Kai},
title = {Coordinated Expression of Stathmin Family Members by Far Upstream
Sequence Element-Binding Protein-1 Increases Motility in Non-Small
Cell Lung Cancer},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {2234--2243},
number = {6},
month = mar,
abstract = {Dynamic instability of the microtubule network modulates processes
such as cell division and motility, as well as cellular morphology.
Overexpression of the microtubule-destabilizing phosphoprotein stathmin
is frequent in human malignancies and represents a promising therapeutic
target. Although stathmin inhibition gives rise to antineoplastic
effects, additional and functionally redundant microtubule-interacting
proteins may attenuate the efficiency of this therapeutic approach.
We have systematically analyzed the expression and potential protumorigenic
effects of stathmin family members in human non-small cell lung cancer
(NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed
in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues
and induced tumor cell proliferation, migration, and matrix invasion
in respective cell lines. Accordingly, reduced stathmin and SCLIP
levels affected cell morphology and were associated with a less malignant
phenotype. Combined inhibition of both factors caused additive effects
on tumor cell motility, indicating partial functional redundancy.
Because stathmin and SCLIP expression significantly correlated in
NSCLC tissues, we searched for common upstream regulators and identified
the far upstream sequence element-binding protein-1 (FBP-1) as a
pivotal inducer of several stathmin family members. Our results indicate
that the coordinated overexpression of microtubule-destabilizing
factors by FBP-1 is a critical step to facilitate microtubule dynamics
and subsequently increases proliferation and motility of tumor cells.
[Cancer Res 2009;69(6):2234-43]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/6/2234}
}
@ARTICLE{Singh2011,
author = {Singh, A. and Friden, V. and Dasgupta, I. and Foster, R. R. and Welsh,
G. I. and Tooke, J. E. and Haraldsson, B. and Mathieson, P. W. and
Satchell, S. C.},
title = {High glucose causes dysfunction of the human glomerular endothelial
glycocalyx},
journal = {Am J Physiol Renal Physiol},
year = {2011},
volume = {300},
pages = {F40--48},
number = {1},
month = jan,
abstract = {The endothelial glycocalyx is a gel-like layer which covers the luminal
side of blood vessels. The glomerular endothelial cell (GEnC) glycocalyx
is composed of proteoglycan core proteins, glycosaminoglycan (GAG)
chains, and sialoglycoproteins and has been shown to contribute to
the selective sieving action of the glomerular capillary wall. Damage
to the systemic endothelial glycocalyx has recently been associated
with the onset of albuminuria in diabetics. In this study, we analyze
the effects of high glucose on the biochemical structure of the GEnC
glycocalyx and quantify functional changes in its protein-restrictive
action. We used conditionally immortalized human GEnC. Proteoglycans
were analyzed by Western blotting and indirect immunofluorescence.
Biosynthesis of GAG was analyzed by radiolabeling and quantified
by anion exchange chromatography. FITC-albumin was used to analyze
macromolecular passage across GEnC monolayers using an established
in vitro model. We observed a marked reduction in the biosynthesis
of GAG by the GEnC under high-glucose conditions. Further analysis
confirmed specific reduction in heparan sulfate GAG. Expression of
proteoglycan core proteins remained unchanged. There was also a significant
increase in the passage of albumin across GEnC monolayers under high-glucose
conditions without affecting interendothelial junctions. These results
reproduce changes in GEnC barrier properties caused by enzymatic
removal of heparan sulfate from the GEnC glycocalyx. They provide
direct evidence of high glucose-induced alterations in the GEnC glycocalyx
and demonstrate changes to its function as a protein-restrictive
layer, thus implicating glycocalyx damage in the pathogenesis of
proteinuria in diabetes.},
comment = {10.1152/ajprenal.00103.2010},
url = {http://ajprenal.physiology.org/cgi/content/abstract/300/1/F40}
}
@ARTICLE{Singh2007,
author = {Singh, Arun D and Sisley, Karen and Xu, Yaomin and Li, Jianbo and
Faber, Pieter and Plummer, Sarah J and Mudhar, Hardeep S and Rennie,
Ian G and Kessler, Patricia M and Casey, Graham and Williams, Bryan
G},
title = {Reduced expression of autotaxin predicts survival in uveal melanoma},
journal = {Br J Ophthalmol},
year = {2007},
volume = {91},
pages = {1385--1392},
number = {10},
month = oct,
abstract = {AimIn an effort to identify patients with uveal melanoma at high risk
of metastasis, the authors undertook correlation of gene expression
profiles with histopathology data and tumour-related mortality. MethodsThe
RNA was isolated from 27 samples of uveal melanoma from patients
who had consented to undergo enucleation, and transcripts profiled
using a cDNA array comprised of sequence-verified cDNA clones representing
approximately 4000 genes implicated in cancer development. Two multivariate
data mining techniques--hierarchical cluster analysis and multidimensional
scaling--were used to investigate the grouping structure in the gene
expression data. Cluster analysis was performed with a subset of
10 000 randomly selected genes and the cumulative contribution of
all the genes in making the correct grouping was recorded. ResultsHierarchical
cluster analysis and multidimensional scaling revealed two distinct
classes. When correlated with the data on metastasis, the two molecular
classes corresponded very well to the survival data for the 27 patients.
Thirty two discrete genes (corresponding to 44 probe sets) that correctly
defined the molecular classes were selected. A single gene (ectonucleotide
pyrophosphatase/phosphodiesterase 2; autotaxin) could classify the
molecular types. The expression pattern was confirmed using real-time
quantitative PCR. ConclusionsGene expression profiling identifies
two distinct prognostic classes of uveal melanoma. Underexpression
of autotaxin in class 2 uveal melanoma with a poor prognosis needs
to be explored further.},
url = {http://bjo.bmj.com/cgi/content/abstract/91/10/1385}
}
@ARTICLE{Singh2007a,
author = {Singh, Amar M. and Hamazaki, Takashi and Hankowski, Katherine E.
and Terada, Naohiro},
title = {A Heterogeneous Expression Pattern for Nanog in Embryonic Stem Cells},
journal = {STEM CELLS},
year = {2007},
volume = {25},
pages = {2534--2542},
number = {10},
abstract = {Abstract 10.1634/stemcells.2007-0126.abs Nanog is a critical homeodomain
factor responsible for maintaining embryonic stem (ES) cell self-renewal
and pluripotency. Of interest, Nanog expression is not homogeneous
in the conventional culture of murine ES cells. A Nanog-high population
expresses markers for pluripotent ES cells, whereas a Nanog-low population
expresses markers for primitive endoderm, such as Gata6. Since the
inner cell mass of early blastocysts has recently been reported to
be heterogeneous in terms of Nanog and Gata6 expression, ES cells
appear to closely resemble the developing stage from which they originate.
We further demonstrate that Nanog can directly repress Gata6 expression
through its binding to the proximal promoter region of the Gata6
gene and that overexpression of Nanog reduces heterogeneity during
ES cell maintenance. Interestingly, Nanog heterogeneity does not
correlate with the heterogeneous expression of stage-specific embryonic
antigen-1, suggesting that multiple but overlapping levels of heterogeneity
may exist in ES cells. These findings provide insight into the factors
that control ES cell self-renewal and the earliest lineage commitment
to primitive endoderm while also suggesting methods to promote homogeneity
during ES cell maintenance. Disclosure of potential conflicts of
interest is found at the end of this article.},
issn = {1549-4918},
keywords = {Embryonic stem cells, Nanog, Gata6, Heterogeneity, Primitive endoderm},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-0126}
}
@ARTICLE{Singh2009,
author = {Singh, Dharam and Chang, Ssu-Jean and Lin, Pei-Hsun and Averina,
Olga V. and Kaberdin, Vladimir R. and Lin-Chao, Sue},
title = {Regulation of ribonuclease E activity by the L4 ribosomal protein
of Escherichia coli},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {864--869},
number = {3},
month = jan,
abstract = {Whereas ribosomal proteins (r-proteins) are known primarily as components
of the translational machinery, certain of these r-proteins have
been found to also have extraribosomal functions. Here we report
the novel ability of an r-protein, L4, to regulate RNA degradation
in Escherichia coli. We show by affinity purification, immunoprecipitation
analysis, and E. coli two-hybrid screening that L4 interacts with
a site outside of the catalytic domain of RNase E to regulate the
endoribonucleolytic functions of the enzyme, thus inhibiting RNase
E-specific cleavage in vitro, stabilizing mRNAs targeted by RNase
E in vivo, and controlling plasmid DNA replication by stabilizing
an antisense regulatory RNA normally attacked by RNase E. Broader
effects of the L4-RNase E interaction on E. coli transcripts were
shown by DNA microarray analysis, which revealed changes in the abundance
of 65 mRNAs encoding the stress response proteins HslO, Lon, CstA,
YjiY, and YaeL, as well as proteins involved in carbohydrate and
amino acid metabolism and transport, transcription/translation, and
DNA/RNA synthesis. Analysis of mRNA stability showed that the half
lives of stress-responsive transcripts were increased by ectopic
expression of L4, which normally increases along with other r-proteins
in E. coli under stress conditions, and also by inactivation of RNase
E. Our finding that L4 can inhibit RNase E-dependent decay may account
at least in part for the elevated production of stress-induced proteins
during bacterial adaptation to adverse environments.},
url = {http://www.pnas.org/cgi/content/abstract/106/3/864}
}
@ARTICLE{Singh2012,
author = {Manjulata Singh and Aditya Arya and Rajesh Kumar and Kalpana Bhargava
and Niroj Kumar Sethy},
title = {Dietary nitrite attenuates oxidative stress and activates antioxidant
genes in rat heart during hypobaric hypoxia},
journal = {Nitric Oxide},
year = {2012},
volume = {26},
pages = {61 - 73},
number = {1},
abstract = {The nitrite anion represents the circulatory and tissue storage form
of nitric oxide (NO) and a signaling molecule, capable of conferring
cardioprotection and many other health benefits. However, molecular
mechanisms for observed cardioprotective properties of nitrite remain
largely unknown. We have evaluated the NO-like bioactivity and cardioprotective
efficacies of sodium nitrite supplemented in drinking water in rats
exposed to short-term chronic hypobaric hypoxia. We observed that,
nitrite significantly attenuates hypoxia-induced oxidative stress,
modulates HIF-1α stability and promotes NO-cGMP signaling in hypoxic
heart. To elucidate potential downstream targets of nitrite during
hypoxia, we performed a microarray analysis of nitrite supplemented
hypoxic hearts and compared with both hypoxic and nitrite supplemented
normoxic hearts respectively. The analysis revealed a significant
increase in the expression of many antioxidant genes, transcription
factors and cardioprotective signaling pathways which was subsequently
confirmed by qRT-PCR and Western blotting. Conversely, hypoxia exposure
increased oxidative stress, activated inflammatory cytokines, downregulated
ion channels and altered expression of both pro- and anti-oxidant
genes. Our results illustrate the physiological function of nitrite
as an eNOS-independent source of NO in heart profoundly modulating
the oxidative status and cardiac transcriptome during hypoxia.},
doi = {10.1016/j.niox.2011.12.002},
issn = {1089-8603},
keywords = {Nitrite},
url = {http://www.sciencedirect.com/science/article/pii/S1089860311005027}
}
@ARTICLE{Singh2007b,
author = {Singh, M.K. and Scott, T.F. and LaFramboise, W.A. and Hu, F.Z. and
Post, J.C. and Ehrlich, G.D.},
title = {Gene expression changes in peripheral blood mononuclear cells from
multiple sclerosis patients undergoing [beta]-interferon therapy},
journal = {Journal of the Neurological Sciences},
year = {2007},
volume = {258},
pages = {52--59},
number = {1-2},
month = jul,
abstract = {Objective Multiple sclerosis (MS) is a disabling idiopathic inflammatory
disorder with evidence of immune dysfunction. Current therapies for
MS include preparations of [beta]-interferon ([beta]IFN). We studied
the gene expression patterns in peripheral blood mononuclear cells
from relapsing-remitting MS patients undergoing weekly [beta]IFN-1a
therapy (Avonex(TM); 30 mg intramuscular) to identify biomarkers
for [beta]IFN responsiveness.Methods Oligonucleotide microarrays
were used for the comparative analysis of gene expression patterns
from longitudinal PBMC samples taken from five patients undergoing
[beta]IFN therapy.Results On the basis of two-fold changes in expression
levels and statistical analyses we selected a candidate diagnostic
set of 136 genes that were differentially expressed between pretreatment
and IFN-[beta]-1a-treated MS patients. When we applied this gene
set to cluster the specimens according to their expression profiles,
the pretreatment samples clustered in one branch, and acute and chronic
samples following treatment clustered in another branch. However,
the chronic samples from the single clinical non-responder clustered
with the pretreatment branch, suggesting that a possible reversal
of [beta]IFN-induced gene expression may be contributing to the poor
clinical response.Conclusions These 136 genes represent potential
targets for new MS therapeutics and the basis for lack of [beta]IFN
response.},
issn = {0022-510X},
keywords = {Multiple sclerosis, Interferon, Microarrays, VCAM-1, Ephrin},
url = {http://www.sciencedirect.com/science/article/B6T06-4NM5SJK-1/2/a3305f7e9e0d4206e9142bf3fbc8722b}
}
@ARTICLE{Singh2008,
author = {Singh, Mahendra K. and Dadke, Disha and Nicolas, Emmanuelle and Serebriiskii,
Ilya G. and Apostolou, Sinoula and Canutescu, Adrian and Egleston,
Brian L. and Golemis, Erica A.},
title = {A Novel Cas Family Member, HEPL, Regulates FAK and Cell Spreading},
journal = {Mol. Biol. Cell},
year = {2008},
volume = {19},
pages = {1627--1636},
number = {4},
month = apr,
abstract = {For over a decade, p130Cas/BCAR1, HEF1/NEDD9/Cas-L, and Efs/Sin have
defined the Cas (Crk-associated substrate) scaffolding protein family.
Cas proteins mediate integrin-dependent signals at focal adhesions,
regulating cell invasion and survival; at least one family member,
HEF1, regulates mitosis. We here report a previously undescribed
novel branch of the Cas protein family, designated HEPL (for HEF1-Efs-p130Cas-like).
The HEPL branch is evolutionarily conserved through jawed vertebrates,
and HEPL is found in some species lacking other members of the Cas
family. The human HEPL mRNA and protein are selectively expressed
in specific primary tissues and cancer cell lines, and HEPL maintains
Cas family function in localization to focal adhesions, as well as
regulation of FAK activity, focal adhesion integrity, and cell spreading.
It has recently been demonstrated that upregulation of HEF1 expression
marks and induces metastasis, whereas high endogenous levels of p130Cas
are associated with poor prognosis in breast cancer, emphasizing
the clinical relevance of Cas proteins. Better understanding of the
complete protein family should help inform prediction of cancer incidence
and prognosis.},
url = {http://www.molbiolcell.org/cgi/content/abstract/19/4/1627}
}
@ARTICLE{Singh2007c,
author = {Singh, Padmasana and Krishna, Amitabh and Sridaran, Rajagopala},
title = {Localization of gonadotrophin-releasing hormone I, bradykinin and
their receptors in the ovaries of non-mammalian vertebrates},
journal = {Reproduction},
year = {2007},
volume = {133},
pages = {969--981},
number = {5},
month = may,
abstract = {GnRH I and its receptors have been demonstrated in the ovaries of
various vertebrates, but their physiological significance in reproductive
cascade is fragmentary. Bradykinin is a potent GnRH stimulator in
the hypothalamus. In the present study, the presence of GnRH I and
its receptor, and bradykinin and its receptor in the ovaries of non-mammalian
vertebrates were investigated to understand their physiological significance.
GnRH I immunoreactivity in the ovaries of fish, frog, reptile and
bird were mainly found in the oocyte of early growing follicles and
granulosa cells and theca cells of previtellogenic follicles. Vitellogenic
follicles showed mild GnRH immunoreactivity. GnRH I-receptor and
bradykinin were localized in the same cell types of the ovaries of
these vertebrates. The presence of GnRH I, GnRH I-receptor and bradykinin
in the ovaries of these vertebrates was confirmed by immunoblotting.
The presence of GnRH I mRNA was demonstrated in the ovary of vertebrates
using RT-PCR. The ovaries of reptiles and birds showed significantly
higher intensity of immunoreactivity for GnRH I-receptor as compared
with the fish and amphibian. This may have a correlation with the
higher yolk content in the ovary of reptile and bird. These results
suggest the possibility of GnRH I and bradykinin as important regulators
of follicular development and vitellogenesis in the vertebrate ovary.},
url = {http://www.reproduction-online.org/cgi/content/abstract/133/5/969}
}
@ARTICLE{Singh2010,
author = {Singh, Ruchi and Kumar, Dhiraj and Duncan, Robert C. and Nakhasi,
Hira L. and Salotra, Poonam},
title = {Overexpression of histone H2A modulates drug susceptibility in Leishmania
parasites},
journal = {Int J Antimicrob Agents},
year = {2010},
volume = {36},
pages = {50--57},
number = {1},
month = jul,
abstract = {Resistance to antimonials has emerged as a major hurdle to the treatment
and control of visceral leishmaniasis (VL), also know as kala-azar
(KA), the disease caused by Leishmania donovani, in India where >60%
of KA patients are unresponsive to sodium antimony gluconate (SAG)
treatment. Determinants of resistance in laboratory strains are partly
known, however the mechanism operating in field isolates is not well
understood. In microarray-based expression profiling with RNA isolated
from field isolates of drug-resistant and -sensitive L. donovani
parasites, genes encoding histone 1 (H1), histone 2A (H2A), histone
4 (H4), mitogen-activated protein kinase 1 (MAPK1) and two hypothetical
proteins showed significantly higher expression in antimony-resistant
parasites, whilst genes encoding an amino acid transporter showed
higher expression in sensitive parasites. The expression level of
these genes was validated by semiquantitative polymerase chain reaction
(PCR). Furthermore, the higher expression of H1, H2A and MAPK1 was
confirmed at the protein level in resistant isolates. Overexpression
of H2A in a drug-sensitive laboratory strain as well as a field isolate
of L. donovani resulted in conversion of SAG-sensitive Leishmania
parasites into a resistant phenotype. Moreover, H2A overexpression
resulted in a significant decrease in susceptibility towards other
antileishmanial drugs currently in use, i.e. amphotericin B and miltefosine,
pointing to its role in drug resistance.},
issn = {0924-8579},
keywords = {Visceral leishmaniasis, Leishmania, Microarray, Histones, Sodium antimony
gluconate, Drug resistance},
publisher = {Elsevier Science Publishers,},
refid = {S0924-8579(10)00145-7},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0924857910001457?showall=true}
}
@ARTICLE{Singh2005,
author = {Singh, Ruchira and Maganti, Rajanikanth J. and Jabba, Sairam V. and
Wang, Martin and Deng, Glenn and Heath, Joe Don and Kurn, Nurith
and Wangemann, Philine},
title = {Microarray-based comparison of three amplification methods for nanogram
amounts of total RNA},
journal = {Am J Physiol Cell Physiol},
year = {2005},
volume = {288},
pages = {C1179--1189},
number = {5},
month = may,
abstract = {Gene expression profiling using microarrays requires microgram amounts
of RNA, which limits its direct application for the study of nanogram
RNA samples obtained using microdissection, laser capture microscopy,
or needle biopsy. A novel system based on Ribo-SPIA technology (RS,
Ovation-Biotin amplification and labeling system) was recently introduced.
The utility of the RS system, an optimized prototype system for picogram
RNA samples (pRS), and two T7-based systems involving one or two
rounds of amplification (OneRA, Standard Protocol, or TwoRA, Small
Sample Prototcol, version II) were evaluated in the present study.
Mouse kidney (MK) and mouse universal reference (MUR) RNA samples,
0.3 ng to 10 {micro}g, were analyzed using high-density Affymetrix
Mouse Genome 430 2.0 GeneChip arrays. Call concordance between replicates,
correlations of signal intensity, signal intensity ratios, and minimal
fold increase necessary for significance were determined. All systems
amplified partially overlapping sets of genes with similar signal
intensity correlations. pRS amplified the highest number of genes
from 10-ng RNA samples. We detected 24 of 26 genes verified by RT-PCR
in samples prepared using pRS. TwoRA yielded somewhat higher call
concordances than did RS and pRS (91.8% vs. 89.3% and 88.1%, respectively).
Although all target preparation methods were suitable, pRS amplified
the highest number of targets and was found to be suitable for amplification
of as little as 0.3 ng of total RNA. In addition, RS and pRS were
faster and simpler to use than the T7-based methods and resulted
in the generation of cDNA, which is more stable than cRNA.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/288/5/C1179}
}
@ARTICLE{Singh2010d,
author = {Singh, Saurabh and Greene, Robert M. and Pisano, M. Michele},
title = {Arsenate-induced apoptosis in murine embryonic maxillary mesenchymal
cells via mitochondrial-mediated oxidative injury},
journal = {Birth Defects Research Part A: Clinical and Molecular Teratology},
year = {2010},
volume = {88},
pages = {25--34},
number = {1},
abstract = {Abstract 10.1002/bdra.20623.abs BACKGROUND: Arsenic is a ubiquitous
element that is a potential carcinogen and teratogen and can cause
adverse developmental outcomes. Arsenic exerts its toxic effects
through the generation of reactive oxygen species (ROS) that include
hydrogen peroxide (H2O2), superoxide-derived hydroxyl ion, and peroxyl
radicals. However, the molecular mechanisms by which arsenic induces
cytotoxicity in murine embryonic maxillary mesenchymal (MEMM) cells
are undefined. METHODS: MEMM cells in culture were treated with different
concentrations of pentavalent sodium arsenate [As (V)] for 24 or
48 hr and various end points measured. RESULTS: Treatment of MEMM
cells with the pentavalent form of inorganic arsenic resulted in
caspase-mediated apoptosis, accompanied by generation of ROS and
disruption of mitochondrial membrane potential. Treatment with caspase
inhibitors markedly blocked apoptosis. In addition, the free radical
scavenger N-acetylcysteine dramatically attenuated arsenic-mediated
ROS production and apoptosis, and exposure to arsenate increased
Bax and decreased Bcl protein levels in MEMM cells. CONCLUSIONS:
Taken together, these findings suggest that in MEMM cells arsenate-mediated
oxidative injury acts as an early and upstream initiator of the cell
death cascade, triggering cytotoxicity, mitochondrial dysfunction,
altered Bcl/Bax protein ratios, and activation of caspase-9. Birth
Defects Research (Part A), 2010. © 2009 Wiley-Liss, Inc.},
issn = {1542-0760},
keywords = {reactive oxygen species, arsenate, mitochondria, apoptosis, caspases},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bdra.20623}
}
@ARTICLE{Singh2010a,
author = {Singh, Shalini and Vinson, Charles and Gurley, Cathy M. and Nolen,
Greg T. and Beggs, Marjorie L. and Nagarajan, Radhakrishnan and Wagner,
Erwin F. and Parham, David M. and Peterson, Charlotte A.},
title = {Impaired Wnt Signaling in Embryonal Rhabdomyosarcoma Cells from p53/c-fos
Double Mutant Mice},
journal = {Am. J. Pathol.},
year = {2010},
volume = {177},
pages = {2055--2066},
number = {4},
month = oct,
abstract = {Rhabdomyosarcoma is a primitive neoplasm with a poorly understood
etiology that exhibits features of fetal skeletal muscle. It represents
the most frequent malignant soft tissue sarcoma affecting the pediatric
population and is often treated very aggressively. Embryonal rhabdomyosarcoma
(ERMS) and alveolar rhabdomyosarcoma constitute the two major subtypes
and exhibit different molecular features. We investigated one potential
molecular basis for ERMS by using cells derived from tumors produced
in p53-/-/c-fos-/- mice. This model closely recapitulates the timing,
location, molecular markers, and histology seen in human ERMS. A
combined chromatin immunoprecipitation/promoter microarray approach
was used to identify promoters bound by the c-Jun-containing AP-1
complex in the tumor-derived cells that lacked c-Fos. Identification
of the Wnt2 gene and its overexpression in ERMS cells was confirmed
in human rhabdomyosarcoma cell lines and prompted further analysis
of the Wnt signaling pathway. Contrary to our expectations, the canonical
Wnt/{beta}-catenin signaling pathway was down-regulated in ERMS cells
compared with normal myoblasts, and activating this pathway promoted
myogenic differentiation. Furthermore, the identification of both
survivin and sfrp2 through promoter and expression analyses suggested
that increased resistance to apoptosis was associated with the inhibition
of the Wnt signaling pathway. These results suggest that altered
AP-1 activity that leads to the down-regulation of the Wnt pathway
may contribute to the inhibition of myogenic differentiation and
resistance to apoptosis in ERMS cases.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/4/2055}
}
@ARTICLE{Singh2011a,
author = {Singh, Sandeep K. and Bhardwaj, Reetika and Wilczynska, Katarzyna
M. and Dumur, Catherine I. and Kordula, Tomasz},
title = {A Complex of Nuclear Factor I-X3 and STAT3 Regulates Astrocyte and
Glioma Migration through the Secreted Glycoprotein YKL-40},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {39893-39903},
number = {46},
abstract = {Nuclear factor I-X3 (NFI-X3) is a newly identified splice variant
of NFI-X that regulates expression of several astrocyte-specific
markers, such as glial fibrillary acidic protein. Here, we identified
a set of genes regulated by NFI-X3 that includes a gene encoding
a secreted glycoprotein YKL-40. Although YKL-40 expression is up-regulated
in glioblastoma multiforme, its regulation and functions in nontransformed
cells of the central nervous system are widely unexplored. We find
that expression of YKL-40 is activated during brain development and
also differentiation of neural progenitors into astrocytes in vitro.
Furthermore, YKL-40 is a migration factor for primary astrocytes,
and its expression is controlled by both NFI-X3 and STAT3, which
are known regulators of gliogenesis. Knockdown of NFI-X3 and STAT3
significantly reduced YKL-40 expression in astrocytes, whereas overexpression
of NFI-X3 dramatically enhanced YKL-40 expression in glioma cells.
Activation of STAT3 by oncostatin M induced YKL-40 expression in
astrocytes, whereas expression of a dominant-negative STAT3 had a
suppressive effect. Mechanistically, NFI-X3 and STAT3 form a complex
that binds to weak regulatory elements in the YKL-40 promoter and
activates transcription. We propose that NFI-X3 and STAT3 control
the migration of differentiating astrocytes as well as migration
and invasion of glioma cells via regulating YKL-40 expression.},
doi = {10.1074/jbc.M111.257451},
eprint = {http://www.jbc.org/cgi/reprint/286/46/39893.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/46/39893}
}
@ARTICLE{Singh2010b,
author = {Singh, Satya P. and de Camargo, Maristela M. and Zhang, Hongwei H.
and Foley, John F. and Hedrick, Michael N. and Farber, Joshua M.},
title = {Changes in histone acetylation and methylation that are important
for persistent but not transient expression of CCR4 in human CD4+
T cells},
journal = {Eur. J. Immunol.},
year = {2010},
volume = {40},
pages = {3183--3197},
number = {11},
abstract = {Abstract Although regulation of CXCR3 and CCR4 is related to Th1 and
Th2 differentiation, respectively, many CXCR3+ and CCR4+ cells do
not express IFN-γ and/or IL-4, suggesting that the chemokine receptor
genes might be inducible by mechanisms that are lineage-independent.
We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus
IL4 in human CD4+ T cells by analyzing modifications of histone H3.
In naïve cord-blood cells, under nonpolarizing conditions not inducing
IL4, CCR4 was induced to high levels without many of the activation-associated
changes in promoter histone H3 found for both IL4 and CCR4 in Th2
cells. Importantly, CCR4 expression was stable in Th2 cells, but
fell in nonpolarized cells after the cells were rested; this decline
could be reversed by increasing histone acetylation using sodium
butyrate. Patterns of histone H3 modifications in CXCR3+CCR4− and
CXCR3−CCR4+ CD4+ T-cell subsets from adult blood matched those
in cells cultured under polarizing conditions in vitro. Our data
show that high-level lineage-independent induction of CCR4 can occur
following T-cell activation without accessibility-associated changes
in histone H3, but that without such changes expression is transient
rather than persistent.},
issn = {1521-4141},
keywords = {Chemokines, Epigenetics, Histones, Human, T cells},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.201040443}
}
@ARTICLE{Singh2010c,
author = {Singh, Shailendra R. and Billington, Charlotte K. and Sayers, Ian
and Hall, Ian P.},
title = {Can lineage-specific markers be identified to characterize mesenchyme-derived
cell populations in the human airways?},
journal = {Am J Physiol Lung Cell Mol Physiol},
year = {2010},
volume = {299},
pages = {L169--183},
number = {2},
month = aug,
abstract = {Mesenchyme-derived cells in the airway wall including airway smooth
muscle cells, fibroblasts, and myofibroblasts are known to play important
roles in airway remodeling. The lack of specific phenotypical markers
makes it difficult to define these cell populations in primary cultures.
Most relevant studies to date have used animal airway tissues, vascular
tissues, or transformed cell lines with only limited studies attempting
to phenotypically characterize human airway mesenchymal cells. The
objectives of this study were to evaluate reported markers and identify
novel markers to define these cell types. We could not identify any
specific marker to define these cell populations in vitro that permitted
unequivocal identification using immunocytochemistry. However, characteristic
filamentous {alpha}-smooth muscle actin distribution was observed
in a significant ([~]25%) proportion of human airway smooth muscle
cells, whereas this was not observed in airway fibroblasts. A significantly
higher proportion of airway fibroblasts expressed {alpha}1- and {alpha}2-integrin
receptors compared with human airway smooth muscle cells as assessed
by fluorescence activated cell sorting. Global gene expression profiling
identified aldo-keto reductase 1C3 (AKR1C3) and cathepsin K as being
novel markers to define airway smooth muscle cells, whereas integrin-{alpha}8
(ITGA8) and thromboxane synthase 1 (TBXAS1) were identified as novel
airway fibroblast-specific markers, and these findings were validated
by RT-PCR. Ex vivo studies in human airway tissue sections identified
high-molecular weight caldesmon and {alpha}-smooth muscle actin as
being expressed in smooth muscle bundles, whereas ITGA8 and TBXAS1
were absent from these.},
url = {http://ajplung.physiology.org/cgi/content/abstract/299/2/L169}
}
@ARTICLE{Singhal2008,
author = {Singhal, Rohit and Shankar, Kartik and Badger, Thomas M. and Ronis,
Martin J.},
title = {Estrogenic status modulates aryl hydrocarbon receptor--mediated hepatic
gene expression and carcinogenicity},
journal = {Carcinogenesis},
year = {2008},
volume = {29},
pages = {227--236},
number = {2},
month = feb,
abstract = {Estrogenic status is thought to influence the cancer risk in women
and has been reported to affect toxicity of carcinogenic polycyclic
aromatic hydrocarbons (PAHs) in animals. The objective of this study
was to examine the influence of estradiol (E2) on hepatic gene expression
changes mediated by 7,12-dimethylbenz(a)anthracene (DMBA), a potent
PAH. Sprague-Dawley rats were ovariectomized on postnatal day 50
and infused with E2 (5 {micro}g/kg/day) or polyethylene glycol using
osmotic pumps and 14 days later gavaged with DMBA (50 mg/kg) or sesame
oil and killed 24 h thereafter. To understand the mechanism of DMBA-mediated
hepatocarcinogenicity in the presence of E2, microarray analysis
(Rat 230 2.0 Affymetrix-GeneChip) was performed. Two hundred and
sixteen genes were downregulated; whereas, 106 genes were upregulated
significantly ({+/-}1.5-fold, P < 0.05) by DMBA treatment. Hierarchical
clustering revealed that the expression profile of 39 genes, regulated
by DMBA, was significantly modified by E2 supplementation. Interestingly,
71 genes were uniquely modulated in the combined treatment of DMBA
and E2, but not by either treatment alone. Results from chromatin
immunoprecipitation assay demonstrate that in animals cotreated with
E2 and DMBA, there was enhanced recruitment of estrogen receptor-{alpha}
to the regulatory regions of CYP1A1 and aryl hydrocarbon receptor
(AhR) genes compared with that observed in animals treated with DMBA
alone. E2 supplementation leads to increased DMBA-induced CYP1A1
transcription, while the AhR gene was upregulated in the presence
of E2 +DMBA only. Our data suggest that estrogenic status is (i)
important in AhR regulation and can influence the effects of xenobiotics
and (ii) may be an important factor in DMBA-mediated carcinogenicity.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/29/2/227}
}
@ARTICLE{Singleton2008,
author = {Singleton, Belinda K. and Burton, Nicholas M. and Green, Carole and
Brady, R. Leo and Anstee, David J.},
title = {Mutations in EKLF/KLF1 form the molecular basis of the rare blood
group In(Lu) phenotype},
journal = {Blood},
year = {2008},
volume = {112},
pages = {2081--2088},
number = {5},
month = sep,
abstract = {Comparison of normal erythroblasts and erythroblasts from persons
with the rare In(Lu) type of Lu(a-b-) blood group phenotype showed
increased transcription levels for 314 genes and reduced levels for
354 genes in In(Lu) cells. Many erythroid-specific genes (including
ALAS2, SLC4A1) had reduced transcript levels, suggesting the phenotype
resulted from a transcription factor abnormality. A search for mutations
in erythroid transcription factors showed mutations in the promoter
or coding sequence of EKLF in 21 of 24 persons with the In(Lu) phenotype.
In all cases the mutant EKLF allele occurred in the presence of a
normal EKLF allele. Nine different loss-of-function mutations were
identified. One mutation abolished a GATA1 binding site in the EKLF
promoter (-124T>C). Two mutations (Leu127X; Lys292X) resulted in
premature termination codons, 2 (Pro190LeufsX47; Arg319GlufsX34)
in frameshifts, and 4 in amino acid substitution of conserved residues
in zinc finger domain 1 (His299Tyr) or domain 2 (Arg328Leu; Arg328His;
Arg331Gly). Persons with the In(Lu) phenotype have no reported pathology,
indicating that one functional EKLF allele is sufficient to sustain
human erythropoiesis. These data provide the first description of
inactivating mutations in human EKLF and the first demonstration
of a blood group phenotype resulting from mutations in a transcription
factor.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/5/2081}
}
@ARTICLE{SinhaRoy2008,
author = {Sinha Roy, Somdutta and Mukhopadhyay, Sutapa and Mukherjee, Shyamali
and Das, Salil K.},
title = {Breast cancer is associated with an increase in the activity and
expression of cholinephosphotransferase in rats},
journal = {Life Sciences},
year = {2008},
volume = {83},
pages = {661--665},
number = {19-20},
month = nov,
abstract = {Aim The present study aims to establish that cholinephosphotransferase
(CPT), the terminal enzyme for the de novo biosynthesis of phosphatidylcholine
(PC), can be used as a biomarker for breast cancer in an animal model.Main
methods Breast cancer was induced by intragastric administration
of dimethylbenz(a)anthracene (DMBA) in rats. The activity and expression
of CPT were compared between normal breast tissues and breast tumors.
To establish possible mechanistic model, we looked into other enzymes
of PC biosynthesis as well as c-fos protein expression and DNA binding.Key
findings CPT enzyme activity and its expression were significantly
higher in breast cancer tissues relative to normal breast tissues.
Corresponding to the increase in the CPT activity and its expression,
c-fos activity and its expression were also increased in breast tumors.Significance
The present study suggests that increased CPT activity and expression
is associated with DMBA-induced breast cancer development.},
issn = {0024-3205},
keywords = {Cholinephosphotransferase, Gene expression, Phosphatidylcholine, Breast
cancer},
url = {http://www.sciencedirect.com/science/article/B6T99-4TJTXDX-2/2/ff874ba6b1d66e7a3be30ebe64a02854}
}
@ARTICLE{Sinha2010,
author = {Sinha, Anshu and Shahzad, Khurram and Latif, Farhana and Cadeiras,
Martin and Von Bayern, Manuel Prinz and Oz, Simin and Naka, Yoshifumi
and Deng, Mario C.},
title = {Peripheral blood mononuclear cell transcriptome profiles suggest
T-cell immunosuppression after uncomplicated mechanical circulatory
support device surgery},
journal = {Human Immunology},
year = {2010},
volume = {71},
pages = {164--169},
number = {2},
month = feb,
abstract = {Mechanical circulatory support device (MCSD) surgery in patients with
advanced heart failure patients is often complicated by infections
that are linked to altered cell-mediated immunity. Using a transcriptome-wide
peripheral blood mononuclear cell (PBMC) gene expression profiling
approach, we analyzed expression patterns directly before and after
MCSD implantation in 11 patients who had an uncomplicated course
after MCSD implantation (Day 0-24 hours before, Day 1-24 hours after,
and Day 7-1 week after implantation). Data were analyzed using Significance
Analysis of Microarrays (SAM) and High-Throughput GoMiner on post-implantation
profiles (Day 1, Day 7) in comparison with baseline (Day 0). Day1
profiles included differential expression of 821 genes (SAM, FDR
<0.1, fold change >1.5), enriching >60 Gene Ontology (GO) categories.
Grouping by component genes revealed GO clusters, which we term "interleukin
related" (primarily upregulated), "T-cell related" (primarily downregulated),
and "apoptosis related" (both up- and down-regulated genes). Day
7 profiles included GO categories related to repair processes. In
conclusion, transcriptome-wide expression profiling of PBMCs suggests
a response pattern to MCSD implantation of inflammatory activation
and simultaneous T-cell suppression.},
issn = {0198-8859},
keywords = {Gene expression profiling, Peripheral blood mononuclear cells, Mechanical
circulatory support device implantation, T-cell immunosuppression,
Infection},
url = {http://www.sciencedirect.com/science/article/B6T3B-4XK455C-4/2/ad8e7856a56a73a93abbbda4b5a02c77}
}
@ARTICLE{Sinicrope2011,
author = {Sinicrope, Frank A. and Broaddus, Russell and Joshi, Nina and Gerner,
Eugene and Half, Elizabeth and Kirsch, Ilan and Lewin, Jan and Morlan,
Bruce and Hong, Waun Ki},
title = {Evaluation of Difluoromethylornithine for the Chemoprevention of
Barrett's Esophagus and Mucosal Dysplasia},
journal = {Cancer Prevention Research},
year = {2011},
volume = {4},
pages = {829-839},
number = {6},
abstract = {Patients with Barrett's esophagus (BE) and dysplasia are candidates
for chemopreventive strategies to reduce cancer risk. We determined
the effects of difluoromethylornithine (DMFO) on mucosal polyamines,
gene expression, and histopathology in BE. Ten patients with BE and
low-grade dysplasia participated in a single-arm study of DFMO (0.5
g/m2/d) given continuously for 6 months. Esophagoscopy with biopsies
was conducted at baseline, 3, 6, and 12 months. Dysplasia was graded
by a gastrointestinal pathologist. Audiology was assessed (at baseline
and at 6 months). Mucosal polyamines were measured by high-performance
liquid chromatography. Microarray-based gene expression was analyzed
using a cDNA two-color chip. DFMO suppressed levels of the polyamines
putrescine (P = 0.02) and spermidine (P = 0.02) and the spermidine/spermine
ratio (P < 0.01) in dysplastic BE (6 months vs. baseline) that persisted
at 6 months following drug cessation. Among the top 25 modulated
genes, we found those regulating p53-mediated cell signaling (RPL11),
cell-cycle regulation (cyclin E2), and cell adhesion and invasion
(Plexin1). DFMO downregulated Kruppel-like factor 5 (KLF5), a transcription
factor promoting cell proliferation, and suppressed RFC5 whose protein
interacts with proliferating cell nuclear antigen. Histopathology
showed regression of dysplasia (n = 1), stable disease (n = 8), and
progression to high-grade dysplasia (n = 1). Polyamines were suppressed
in the responder to a greater extent than in stable cases. DFMO was
well tolerated, and one patient had subclinical, unilateral ototoxicity.
DFMO suppressed mucosal polyamines and modulated genes that may be
mechanistically related to its chemopreventive effect. Further study
of DFMO for the chemoprevention of esophageal cancer in BE patients
is warranted. Cancer Prev Res; 4(6); 829-39. (C)2011 AACR.},
doi = {10.1158/1940-6207.CAPR-10-0243},
eprint = {http://cancerpreventionresearch.aacrjournals.org/cgi/reprint/4/6/829.pdf},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/4/6/829}
}
@ARTICLE{Sinnamon2008,
author = {Sinnamon, Mark J. and Carter, Kathy J. and Sims, Lauren P. and LaFleur,
Bonnie and Fingleton, Barbara and Matrisian, Lynn M.},
title = {A protective role of mast cells in intestinal tumorigenesis},
journal = {Carcinogenesis},
year = {2008},
volume = {29},
pages = {880--886},
number = {4},
month = apr,
abstract = {Mast cells have been observed in numerous types of tumors; however,
their role in carcinogenesis remains poorly understood. The majority
of epidemiological evidence suggests a negative association between
the presence of mast cells and tumor progression in breast, lung
and colonic neoplasms. Intestinal adenomas in the multiple intestinal
neoplasia (Min, APCMin/+) mouse displayed increased numbers of mast
cells and increased abundance of mast cell-associated proteinases
as determined by transcriptional profiling with the Hu/Mu ProtIn
microarray. To examine the role of mast cells in intestinal tumorigenesis,
a mutant mouse line deficient in mast cells, Sash mice (c-kitW-sh/W-sh),
was crossed with the Min mouse, a genetic model of intestinal neoplasia.
The resulting mast cell-deficient Min-Sash mice developed 50% more
adenomas than littermate controls and the tumors were 33% larger
in Min-Sash mice. Mast cell deficiency did not affect tumor cell
proliferation; however, apoptosis was significantly inhibited in
mast cell-deficient mice. Mast cells have been shown to act as critical
upstream regulators of numerous inflammatory cells. Neutrophil, macrophage
and T cell populations were similar between Min and Min-Sash mice;
however, eosinophils were significantly less abundant in tumors obtained
from Min-Sash animals. These results indicate a protective, antitumor
role of mast cells in a genetic model of early-stage intestinal tumorigenesis.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/29/4/880}
}
@ARTICLE{Sinville2007,
author = {Sinville, Rondedrick and Soper, Steven A.},
title = {High resolution DNA separations using microchip electrophoresis},
journal = {J. Sep. Science},
year = {2007},
volume = {30},
pages = {1714--1728},
number = {11},
abstract = {Abstract 10.1002/jssc.200700150.abs Planar microfluidic devices have
emerged as effective tools for the electrophoretic separation of
a variety of different DNA inputs. The advancement of this miniaturized
platform was inspired initially by demands placed on electrophoretic
performance metrics by the human genome project and has provided
a viable alternative to slab gel and even capillary formats due to
its ability to offer high resolution separations of nucleic acid
materials in a fraction of the time associated with its predecessors,
consumption of substantially less sample and reagents while maintaining
the ability to perform many separations in parallel for realizing
ultra-high throughputs. Another compelling advantage of this separation
platform is that it offers the potential for integrating front-end
sample preprocessing steps onto the separation device eliminating
the need for manual sample handling. This review aims to compile
a recent survey of various electrophoretic separations using either
glass or polymer-based microchips in the areas of genotyping and
DNA sequencing as well as those involving the growing field of DNA-based
forensics.},
issn = {1615-9314},
keywords = {DNA diagnostics, DNA forensics, DNA sequencing, Microchip CE},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/jssc.200700150}
}
@ARTICLE{Sinzelle2011,
author = {Sinzelle, L. and Carradec, Q. and Paillard, E. and Bronchain, O.
J. and Pollet, N.},
title = {Characterization of a Xenopus tropicalis Endogenous Retrovirus with
Developmental and Stress-Dependent Expression},
journal = {J. Virol.},
year = {2011},
volume = {85},
pages = {2167--2179},
number = {5},
month = mar,
abstract = {We report on the identification and characterization of XTERV1, a
full-length endogenous retrovirus (ERV) within the genome of the
western clawed frog (Xenopus tropicalis). XTERV1 contains all the
basic genetic elements common to ERVs, including the classical 5'-long
terminal repeat (LTR)-gag-pol-env-3'-LTR architecture, as well as
conserved functional motifs inherent to each retroviral protein.
Using phylogenetic analysis, we show that XTERV1 is related to the
Epsilonretrovirus genus. The X. tropicalis genome harbors a single
full-length copy with intact gag and pol open reading frames that
localizes to the centromeric region of chromosome 5. About 10 full-length
defective copies of XTERV1 are found interspersed in the genome,
and 2 of them could be assigned to chromosomes 1 and 3. We find that
XTERV1 genes are zygotically transcribed in a regulated spatiotemporal
manner during frog development, including metamorphosis. Moreover,
XTERV1 transcription is upregulated under certain cellular stress
conditions, including cytotoxic and metabolic stresses. Interestingly,
XTERV1 Env is found to be homologous to FR47, a protein upregulated
following cold exposure in the freeze-tolerant wood frog (Rana sylvatica).
In addition, we find that R. sylvatica FR47 mRNA originated from
a retroviral element. We discuss the potential role(s) of ERVs in
physiological processes in vertebrates.},
comment = {10.1128/JVI.01979-10},
url = {http://jvi.asm.org/cgi/content/abstract/85/5/2167}
}
@ARTICLE{Sip2010,
author = {Sip, Miroslav and Bystricka, Dagmar and Kmoch, Stanislav and Noskova,
Lenka and Hartmannova, Hana and Dedic, Petr},
title = {Detection of viral infections by an oligonucleotide microarray},
journal = {Journal of Virological Methods},
year = {2010},
volume = {165},
pages = {64--70},
number = {1},
month = apr,
abstract = {The success of DNA expression microarrays has been followed by applications
of this technology to molecular diagnosis, mainly in the fields of
biology and medicine. The experiments described below apply microarray
diagnosis to agriculture. This report presents results of field tests
for a DNA microarray designed to diagnose major viral potato pathogens.
The assays were performed on samples that had been tested previously
for the presence of viral infection by ELISA. RNA isolation methods
were optimised for high sensitivity, using only 3 [mu]g of total
RNA that were reverse transcribed using random hexamers, with the
resulting cDNA hybridised after labelling to an oligonucleotide array.
The results obtained confirm the presence of pathogens indicated
by ELISA and simultaneously reveal other viruses in the same reaction,
showing that this method is appropriate for rapid detection of mixed
viral infections. This observation was verified by subsequent RT-PCR
and sequencing.},
issn = {0166-0934},
keywords = {Parallel detection, Microarrays, Oligonucleotides, Viruses, Potato,
DNA chip},
url = {http://www.sciencedirect.com/science/article/B6T96-4Y7P6PM-1/2/a8d90d0fed2cb8fc5c695d25bad90b08}
}
@ARTICLE{Sipos2010,
author = {Sipos, Wolfgang and Duvigneau, Catharina and Sterz, Fritz and Weihs,
Wolfgang and Krizanac, Danica and Bayegan, Keywan and Graf, Alexandra
and Hartl, Romana and Janata, Andreas and Holzer, Michael and Behringer,
Wilhelm},
title = {Changes in interleukin-10 mRNA expression are predictive for 9-day
survival of pigs in an emergency preservation and resuscitation model},
journal = {Resuscitation},
year = {2010},
volume = {81},
pages = {603--608},
number = {5},
month = may,
abstract = {Aim of the study This study aimed at evaluating (I) the impact of
different intra-arrest hypothermia levels on the expression of selected
cytokines and (II) their prognostic value for 9-day survival.Methods
Female Large White pigs (n = 21, 31-38 kg) were subjected to 15 min
of ventricular fibrillation, followed by intra-arrest cardiopulmonary
bypass cooling for 1, 3, or 5 min achieving brain temperatures (Tbr)
of 30.4 ± 1.6, 24.2 ± 4.6 and 18.8 ± 4.0 °C. After 40 min of controlled
rewarming, pigs were defibrillated and kept at Tbr of 34.5 °C for
20 h, survival was for 9 days. Plasma samples were analysed for interleukin
(IL)-6, tumor necrosis factor-[alpha] (TNF-[alpha]), and IL-10 levels
by ELISA. Total RNA out of peripheral blood mononuclear cells was
analysed by real-time PCR for IL-1, IL-2, IL-4, IL-10, TNF-[alpha],
interferon-[gamma], inducible NO synthase, and heme oxygenase-1 gene
expressions.Results Plasma IL-6 and TNF-[alpha] levels significantly
(p = 0.0001 and 0.0003) increased in all animals within 1 h after
resuscitation with no significant differences between groups. Pigs
surviving exhibited a decrease in IL-10 expression between baseline
and intra-arrest values as compared to non-surviving animals, which
showed a slight increase (p = 0.0078). ROC curve analysis revealed
that changes in IL-10 expression had a good prognostic power for
survival to day 9 (area under the curve = 0.882).Conclusion The systemic
inflammatory response syndrome after cardiac arrest was reflected
by a remarkable increase of plasma IL-6 and TNF-[alpha] levels. Intra-arrest
hypothermia levels did not influence the expression of selected cytokines.
As prognostic marker for survival IL-10 was identified with decreasing
mRNA levels during cardiac arrest in survivors.},
issn = {0300-9572},
keywords = {Cardiopulmonary resuscitation (CPR), Heart arrest, Hypothermia, Inflammatory
response, Outcome, Temperature},
url = {http://www.sciencedirect.com/science/article/B6T19-4YD9XFH-1/2/fd62b3db3fb657a929c59627afeb1cc3}
}
@ARTICLE{Sipos2011,
author = {Sipos, Wolfgang and Duvigneau, Catharina J. and Hartl, Romana T.
and Schwendenwein, Ilse},
title = {Exploratory reference intervals on hematology and cellular immune
system of multiparous Large White sows},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {141},
pages = {307--311},
number = {3-4},
month = jun,
abstract = {There is significant lack of basic hematologic and immunological data
in adult sows. Therefore, aim of this study was to provide respective
reference intervals. 32 clinically healthy multiparous Large White
sows aged 33.5 ± 9.6 months and all of them two months postpartum
were included in this study. Mean erythrocyte count was 5.5 ± 0.7 × 106/[mu]l
and total leukocyte count was 12.1 ± 2.1 × 103/[mu]l. Proportion
of lymphocytes was 44.7 ± 10.2% and of neutrophils 41.6 ± 11.0%.
The ratio of naïve T helper (Th) cells to memory Th cells was 1:3.1
and the ratio of Th cells to cytotoxic T cells (CTLs) was 1:4.2.
Proportions of regulatory T cells, NK cells, and CD21+ B cells were
lower (3.1, 2.6, and 6.0%) than those of memory Th cells ranging
from 8.8 to 27.5% depending on the activation status and CTLs with
37.3%. [gamma][delta] T cells were found at comparably high numbers
(19.1%). Flow cytometric measurement of intracellular cytokines in
PBMCs revealed marginal levels for IL-1[beta], IL-2, IL-4, IL-6,
IL-10, and IL-12p35, but remarkable levels for TNF-[alpha] and IFN-[gamma].
Highest mRNA levels were found for IL-1, IL-10, and TNF-[alpha],
with TNF-[alpha] showing the least inter-individual variation.},
issn = {0165-2427},
keywords = {Cytokines, Leukocyte phenotypes, Pig},
url = {http://www.sciencedirect.com/science/article/pii/S0165242711000900}
}
@ARTICLE{Siracusa2008,
author = {Siracusa, Mark C. and Reece, Joshua J. and Urban, Joseph F., Jr.
and Scott, Alan L.},
title = {Dynamics of lung macrophage activation in response to helminth infection},
journal = {J. Leukoc. Biol.},
year = {2008},
volume = {84},
pages = {1422--1433},
number = {6},
month = dec,
abstract = {Most of our understanding of the development and phenotype of alternatively
activated macrophages (AAMs) has been obtained from studies investigating
the response of bone marrow- and peritoneal-derived cells to IL-4
or IL-13 stimulation. Comparatively little is known about the development
of AAMs in the lungs, and how the complex signals associated with
pulmonary inflammation influence the AAM phenotype. Here, we use
Nippostrongylus brasiliensis to initiate AAM development and define
the dynamics of surface molecules, gene expression, and cell function
of macrophages isolated from lung tissue at different times postinfection
(PI). Initially, lung macrophages take on a foamy phenotype, up-regulate
MHC and costimulatory molecules, express reduced levels of TNF and
IL-12, and undergo proliferation. Cells isolated between days 8 and
15 PI adopt a dense, granular phenotype and exhibit reduced levels
of costimulatory molecules and elevated levels of programmed death
ligand-1 (PDL-1) and PDL-2 and an increase in IL-10 expression. Functionally,
AAMs isolated on days 13-15 PI demonstrate an enhanced capacity to
take up and sequester antigen. However, these same cells did not
mediate antigen-specific T cell proliferation and dampened the proliferation
of CD3/CD28-activated CD4+ T cells. These data indicate that the
alternative activation of macrophages in the lungs, although initiated
by IL-4/IL-13, is a dynamic process that is likely to be influenced
by other immune and nonimmune factors in the pulmonary environment.},
url = {http://www.jleukbio.org/cgi/content/abstract/84/6/1422}
}
@ARTICLE{Sircar2012,
author = {Kanishka Sircar and Heng Huang and Limei Hu and David Cogdell and
Jasreman Dhillon and Vassiliki Tzelepi and Eleni Efstathiou and Ismaël
H. Koumakpayi and Fred Saad and Dijun Luo and Tarek A. Bismar and
Ana Aparicio and Patricia Troncoso and Nora Navone and Wei Zhang},
title = {Integrative Molecular Profiling Reveals Asparagine Synthetase Is
a Target in Castration-Resistant Prostate Cancer},
journal = {The American Journal of Pathology},
year = {2012},
pages = { - },
number = {0},
abstract = {The identification of new and effective therapeutic targets for the
lethal, castration-resistant stage of prostate cancer (CRPC) has
been challenging because of both the paucity of adequate frozen tissues
and a lack of integrated molecular analysis. Therefore, in this study,
we performed a genomewide analysis of DNA copy number alterations
from 34 unique surgical CRPC specimens and 5 xenografts, with matched
transcriptomic profiling of 25 specimens. An integrated analysis
of these data revealed that the asparagine synthetase (ASNS) gene
showed a gain in copy number and was overexpressed at the transcript
level. The overexpression of ASNS was validated by analyzing other
public CRPC data sets. ASNS protein expression, as detected by reversed-phase
protein lysate array, was tightly correlated with gene copy number.
In addition, ASNS protein expression, as determined by IHC analysis,
was associated with progression to a therapy-resistant disease state
in TMAs that included 77 castration-resistant and 40 untreated prostate
cancer patient samples. Knockdown of ASNS by small-interfering RNAs
in asparagine-deprived media led to growth inhibition in both androgen-responsive
lymph node and castration-resistant (ie, C4-2B) prostate cancer cell
lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30).
Together, our results suggest that ASNS is up-regulated in cases
of CRPC and that depletion of asparagine using ASNS inhibitors will
be a novel strategy for targeting CRPC cells.},
doi = {10.1016/j.ajpath.2011.11.030},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011010984}
}
@ARTICLE{Sircoulomb2010,
author = {Sircoulomb, Fabrice and Bekhouche, Ismahane and Finetti, Pascal and
Adélaïde, José and Hamida, Azza and Bonansea, Julien and Raynaud,
Stéphane and Innocenti, Charlène and Charafe-Jauffret, Emmanuelle
and Tarpin, Carole and Ayed, Farhat and Viens, Patrice and Jacquemier,
Jocelyne and Bertucci, François and Birnbaum, Daniel and Chaffanet,
Max},
title = {Genome profiling of ERBB2-amplified breast cancers},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {539},
number = {1},
abstract = {BACKGROUND:Around 20% of breast cancers (BC) show ERBB2 gene amplification
and overexpression of the ERBB2 tyrosine kinase receptor. They are
associated with a poor prognosis but can benefit from targeted therapy.
A better knowledge of these BCs, genomically and biologically heterogeneous,
may help understand their behavior and design new therapeutic strategies.METHODS:We
defined the high resolution genome and gene expression profiles of
54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative
genomic hybridization and whole-genome DNA microarrays. Expression
of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was
assessed by immunohistochemistry to evaluate the functional ERBB2
status and identify co-expressions.RESULTS:First, we identified the
ERBB2-C17orf37-GRB7 genomic segment as the minimal common 17q12-q21
amplicon, and CRKRS and IKZF3 as the most frequent centromeric and
telomeric amplicon borders, respectively. Second, GISTIC analysis
identified 17 other genome regions affected by copy number aberration
(CNA) (amplifications, gains, losses). The expression of 37 genes
of these regions was deregulated. Third, two types of heterogeneity
were observed in ERBB2-amplified BCs. The genomic profiles of estrogen
receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were
different. The WNT/ß-catenin signaling pathway was involved in ER-
ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes
associated with ER+ ERBB2-amplified BCs. The size of the ERBB2 amplicon
was different in inflammatory (IBC) and non-inflammatory BCs. ERBB2-amplified
IBCs were characterized by the downregulated and upregulated mRNA
expression of ten and two genes in proportion to CNA, respectively.
IHC results showed (i) a linear relationship between ERBB2 gene amplification
and its gene and protein expressions with a good correlation between
ERBB2 expression and phosphorylation status; (ii) a potential signaling
cross-talk between EGFR or IGF1R and ERBB2, which could influence
response of ERBB2-positive BCs to inhibitors. FOXA1 was frequently
coexpressed with ERBB2 but its expression did not impact on the outcome
of patients with ERBB2-amplified tumors.CONCLUSION:We have shown
that ER+ and ER- ERBB2-amplified BCs are different, distinguished
ERBB2 amplicons in IBC and non-IBC, and identified genomic features
that may be useful in the design of alternative therapeutical strategies.},
doi = {10.1186/1471-2407-10-539},
issn = {1471-2407},
pubmedid = {20932292},
url = {http://www.biomedcentral.com/1471-2407/10/539}
}
@ARTICLE{Sircoulomb2011,
author = {Sircoulomb, Fabrice and Nicolas, Nathalie and Ferrari, Anthony and
Finetti, Pascal and Bekhouche, Ismahane and Rousselet, Estelle and
Lonigro, Aurélie and Adélaïde, José and Baudelet, Emilie and
Esteyriès, Séverine and Wicinski, Julien and Audebert, Stéphane
and Charafe-Jauffret, Emmanuelle and Jacquemier, Jocelyne and Lopez,
Marc and Borg, Jean-Paul and Sotiriou, Christos and Popovici, Cornel
and Bertucci, François and Birnbaum, Daniel and Chaffanet, Max and
Ginestier, Christophe},
title = {ZNF703 gene amplification at 8p12 specifies luminal B breast cancer},
journal = {EMBO Molecular Medicine},
year = {2011},
volume = {3},
pages = {153--166},
number = {3},
abstract = {Abstract Luminal B breast cancers represent a fraction of oestrogen
receptor (ER)-positive tumours associated with poor recurrence-free
and disease-specific survival in all adjuvant systemic treatment
categories including hormone therapy alone. Identification of specific
signalling pathways driving luminal B biology is paramount to improve
treatment. We have studied 100 luminal breast tumours by combined
analysis of genome copy number aberrations and gene expression. We
show that amplification of the ZNF703 gene, located in chromosomal
region 8p12, preferentially occurs in luminal B tumours. We explored
the functional role of ZNF703 in luminal B tumours by overexpressing
ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we
identified ZNF703 as a co-factor of a nuclear complex comprising
DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation
of stem cell-related gene expression leading to an increase in cancer
stem cells. Moreover, we show that ZNF703 is implicated in the regulation
of ER and E2F1 transcription factor. These findings point out the
prominent role of ZNF703 in transcription modulation, stem cell regulation
and luminal B oncogenesis.→See accompanying Closeup by Vessela
Kristensen DOI 10.1002/emmm201100128},
doi = {10.1002/emmm.201100121},
issn = {1757-4684},
keywords = {8p11 amplification, breast cancer, cancer stem cell, luminal B, ZNF703},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/emmm.201100121}
}
@ARTICLE{Siripurapu2005,
author = {Siripurapu, Veeraiah and Meth, Jennifer and Kobayashi, Noriko and
Hamaguchi, Masaaki},
title = {DBC2 Significantly Influences Cell-cycle, Apoptosis, Cytoskeleton
and Membrane-trafficking Pathways},
journal = {Journal of Molecular Biology},
year = {2005},
volume = {346},
pages = {83--89},
number = {1},
month = feb,
abstract = {The tumor suppressor DBC2 belongs to a previously uncharacterized
gene family, RHOBTB (Bric-a-brac, Tramtrack, Broad-complex). The
biological roles of RHOBTB proteins, including DBC2, remain unclear.
To understand the physiological functions of DBC2, a global approach
was applied. Expression of DBC2 was manipulated in HeLa cells and
RNA profiling of the cells was performed by microarray analyses.
DBC2 was introduced into HeLa cells by a mammalian expression vector
with a constitutive promoter. DBC2 knockdown was achieved by RNA
interference with small interfering RNA. RNA profiles of these samples
were performed by microarray analysis using Affymetrix GeneChip HG-U133A
2.0. The microarray data were analyzed by Microarray Suite 5.0 (MAS
5.0) and Robust Multichip Average (RMA). A list of genes whose expression
was significantly altered (p<0.001) was generated and overlaid onto
a cellular pathway map in the Ingenuity Systems' Pathway Knowledge
Base (Winter'04 Release). Two networks were found to react substantially
to DBC2 expression; namely, more than half of participating genes
are affected. One of the networks regulates cell growth through cell-cycle
control and apoptosis. The other network is related to cytoskeleton
and membrane trafficking. Our findings suggest that the biological
roles of DBC2 are related directly and/or indirectly to these cellular
machineries.},
issn = {0022-2836},
keywords = {DBC2, tumor suppressor, RHOBTB, microarray, pathway analysis},
url = {http://www.sciencedirect.com/science/article/B6WK7-4DXBTC1-2/2/c5f6997da90f3981336994882cdbbbec}
}
@ARTICLE{Sirotnak2004,
author = {Sirotnak, F.M. and She, Yuhong and Khokhar, Nushmia Z. and Hayes,
Paula and Gerald, William and Scher, Howard I.},
title = {Microarray analysis of prostate cancer progression to reduced androgen
dependence: Studies in unique models contrasts early and late molecular
events},
journal = {Mol. Carcinog.},
year = {2004},
volume = {41},
pages = {150--163},
number = {3},
abstract = {Abstract 10.1002/mc.20051.abs Three unique variants of the CWR22 human
prostate cancer xenograft model (CWR22LD1, LD2, and LD3) with a decrease
in dependence on androgens were selected under noncastrate conditions,
i.e., by outgrowth after transplantation into male NCR (AT) nu mice
without testosterone supplementation. These variants were unable
to grow in castrated male mice. For comparison, a second set of variants
with even less dependence on androgens (castrate-resistant) were
derived following outgrowth from CWR22 (CWR22Rv1 and RC) or CWRLD1
(CWR22RS) after transplantion in castrated male mice. The androgen
receptor (AR) gene in the CWR22LD variants was transcriptionally
active and was neither mutated nor significantly overexpressed compared
to CWR22. Oligonucleotide microarray analysis showed distinctly different
profiles of dysregulated gene expression among the CWR22LD variants.
Groups of only 26–41 genes were dysregulated greater than threefold
with a different proportion of up versus downregulated genes in each
variant. Only one of the castrate-resistant variants (CWR22Rv1) had
a highly overexpressed AR gene but AR in this variant and the two
other castrate-resistant variants, CWR22 RS and RC, was not mutated
beyond that seen in CWR22. In contrast to the CWR22LD variants, a
total of 342, 295, and 222 genes were dysregulated at least threefold
in CWR22Rv1, CWR22RS, and CWR22RC, respectively, differing as well
in the proportion of up versus downregulated genes. Many of the genes
dysregulated in CWR22LD1, LD2, and LD3 were further dysregulated
in CWR22Rv1, RC, or RS. The most downregulated gene was microseminoprotein
beta (MSPB). Along with cyclin D1, the most upregulated gene by an
order of magnitude compared to other upregulated genes was hepatocyte
growth factor (HGF) (scatter factor). These results suggest that
the onset in the loss of androgen dependence in CWR22 proceeds through
multiple pathways and does not require any direct change in the status
of AR. However, upregulation of other survival pathways like that
involving HGF in these studies could co-activate AR signaling. The
endogenous overexpression of genes regulating sterol biosynthesis
also observed in castrate-resistant CWR22 variants delineated a clinically
relevant, compensatory mechanism for overcoming androgen deprivation
reaffirming a central role for AR signaling in this process. © 2004
Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {androgen-independent prostate cancer, CWR22 microarray, HGF},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20051}
}
@ARTICLE{Sissener2009,
author = {Sissener, N.H. and Bakke, A.M. and Gu, J. and Penn, M.H. and Eie,
E. and Krogdahl, Å. and Sanden, M. and Hemre, G.I.},
title = {An assessment of organ and intestinal histomorphology and cellular
stress response in Atlantic salmon (Salmo salar L.) fed genetically
modified Roundup Ready® soy},
journal = {Aquaculture},
year = {2009},
volume = {298},
pages = {101--110},
number = {1-2},
month = dec,
abstract = {This study was conducted to investigate potential differences between
genetically modified (GM) Roundup Ready® soy and its near-isogenic
maternal line as feed ingredients for Atlantic salmon, with focus
on intestinal changes commonly caused by soybean meal, histomorphology
of other organs and stress response. A 7-month feeding trial was
conducted with an inclusion level of 25% GM soy in the diet. Samples
for histology were collected after 4 months, after 6 months, when
a cross-over of the diet groups was conducted, and at the end of
the trial of the crossed-over groups. Histomorphology of spleen,
head kidney and mid intestine exhibited no differences between the
diet groups, while glycogen deposits in liver were decreased in the
GM fed fish at the final sampling. Common soybean meal-induced changes
of the distal intestine in Atlantic salmon were observed in both
diet groups at all sampling points, within levels expected at the
current inclusion level of soy in the diets. However, mucosal fold
height in the distal intestine was lower in the GM fed group at one
of the three sampling points, and mucosal fold fusion was more pronounced
in this group overall in the trial. A stress test conducted at the
end of the trial gave responses in haematological parameters, plasma
nutrients and mRNA transcription of heat shock protein (HSP) 27 in
both liver and distal intestine, but responses were similar between
the two diet groups, indicating similar ability to handle stress.
The cross-over design, implemented to look at reversibility of potential
GM-effects, proved to be inadequate as the crossing of diet groups
in itself caused responses that would obscure possible minor diet
effects. In conclusion, minor differences were observed between the
diet groups; however, GM soy did not appear to cause any adverse
effects on organ morphology or stress response compared to non-GM
soy.},
issn = {0044-8486},
keywords = {Atlantic salmon, Genetic modification, Roundup Ready® soy, Stress,
Intestine},
url = {http://www.sciencedirect.com/science/article/B6T4D-4XGH09J-2/2/5c1f7812b5970347108fdabac0c93870}
}
@ARTICLE{Sitarz2008,
author = {Sitarz, R. and de Leng, W.W.J. and Leguit, R. and Morsink, F.H.M.
and Polkowski, W.P. and Maciejewski, R. and Offerhaus, G.J.A. and
Milne, A.N.},
title = {Cyclooxygenase-2 dependent regulation of E-cadherin through the transcription
repressors Snail and ZEB1 is limited to conventional gastric cancers
cell lines},
journal = {European Journal of Cancer Supplements},
year = {2008},
volume = {6},
pages = {149--150},
number = {9},
month = jul,
booktitle = {20th Meeting of the European Association for Cancer Research},
issn = {1359-6349},
url = {http://www.sciencedirect.com/science/article/B75GT-4SYF3GT-R3/2/08bee0e7f09eb7ce9e8f0e7149bdafc3}
}
@ARTICLE{Sitniakowsky2011,
author = {Sitniakowsky, L. S. and Later, A. F. L. and van de Watering, L. M.
G. and Bogaerts, M. and Brand, A. and Klautz, R. J. M. and Smit,
N. P. M. and van Hilten, J. A.},
title = {The effect of RBC transfusions on cytokine gene expression after
cardiac surgery in patients developing post-operative multiple organ
failure},
journal = {Transfusion Medicine},
year = {2011},
volume = {21},
pages = {236--246},
number = {4},
abstract = {Aim: To determine the effect of red blood cell (RBC) transfusions
during cardiac surgery on cytokine gene expression (GE) in relation
to multiple organ failure (MOF) development after systemic inflammatory
response syndrome (SIRS).Background: RBC transfusion in cardiac surgery
patients is dose-dependently associated with post-operative MOF,
possibly acting as a second hit after cardiopulmonary bypass.Methods:
For this observational study, 29 patients divided into four groups
of cardiac surgery patients were selected from a randomised controlled
trial (RCT). Group 1: no-RBC, no-MOF (N = 8); group 2: MOF, no-RBC
(N = 7); group 3: RBC, no-MOF (N = 6); group 4: RBC and MOF (N =
8). Selection was based on age, gender, number of (leukocyte-depleted)
RBC transfusions, type and duration of surgery.A 114 cytokine GE
array was applied to blood samples withdrawn before and 24 h after
surgery. Expression of selected genes was confirmed with reverse
transcriptase real time-polymerase chain reaction (RT-PCR).Results:
Nineteen of the 39 detectable genes showed a significant change in
GE after surgery. Confirmed by RT-PCR, transfused MOF patients exhibit
significantly less downregulation of CD40 ligand than control patients.
Patients who would develop MOF show significantly larger increases
in GE of transforming growth factor-α (TGF-α), tumour necrosis
factor (TNF)-superfamily members 10 and 13B (TNFsf10/13B).Conclusions:
When tested at 24 h after surgery, cytokine GE in peripheral blood
leucocytes showed no significant differences between those transfused
and those not transfused. Some alterations were seen in those developing
MOF compared to those who did not, but the findings offer no role
of leukocyte depleted (LD) RBC transfusion in the development of
MOF.},
doi = {10.1111/j.1365-3148.2011.01075.x},
issn = {1365-3148},
keywords = {cardiac surgery, cytokines, gene expression, multiple organ failure,
RBC transfusion},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3148.2011.01075.x}
}
@ARTICLE{Sitras2008,
author = {Sitras, V. and Paulssen, R.H. and Gronaas, H. and Vartun, A. and
Acharya, G.},
title = {Gene expression profile in labouring and non-labouring human placenta
near term},
journal = {Mol. Hum. Reprod.},
year = {2008},
volume = {14},
pages = {61--65},
number = {1},
month = jan,
abstract = {The duration of pregnancy and initiation of labour are thought to
be controlled by fetal, maternal and placental factors. The aim of
this study was to investigate whether labour influences gene expression
in placenta near term. Placental samples were obtained from 27 women
after vaginal delivery (labouring) and 17 women after elective Caesarean
section (non-labouring). All women were Caucasian and had uncomplicated
pregnancies. For global gene expression analysis, 17 human oligo-arrays
were used, representing 24 650 genes each. An empirical Bayes analysis
was applied in order to find differentially expressed genes. About
8000 genes that were represented on the arrays met our quality criteria.
Ninety two genes were down-regulated and 94 genes were up-regulated
in labouring placentas compared to non-labouring placentas. However,
none of these was differentially expressed at a significant level
(>2.5-fold change and a P-value of <0.01). We conclude that gene
expression in near term human placenta is not significantly altered
by labour.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/14/1/61}
}
@ARTICLE{Sitras2009,
author = {Sitras, V. and Paulssen, R.H. and Grønaas, H. and Leirvik, J. and
Hanssen, T.A. and Vårtun, Å. and Acharya, G.},
title = {Differential Placental Gene Expression in Severe Preeclampsia},
journal = {Placenta},
year = {2009},
volume = {30},
pages = {424--433},
number = {5},
month = may,
abstract = {We investigated the global placental gene expression profile in severe
preeclampsia. Twenty-one women were randomly selected from 50 participants
with uncomplicated pregnancies to match 21 patients with severe preeclampsia.
A 30 K Human Genome Survey Microarray v.2.0 (Applied Biosystems)
was used to evaluate the gene expression profile. After RNA isolation,
five preeclamptic placentas were excluded due to poor RNA quality.
The series composed of 37 hybridizations in a one-channel detection
system of chemiluminescence emitted by the microarrays. An empirical
Bayes analysis was applied to find differentially expressed genes.
In preeclamptic placentas 213 genes were significantly (fold-change >= 2
and p <= 0.01) up-regulated and 82 were down-regulated, compared
with normal placentas. Leptin (40 fold), laeverin (10 fold), different
isoforms of [beta]-hCG (3-6 fold), endoglin (4 fold), FLT1 (3 fold)
and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2
fold). Several differentially expressed genes were associated with
Alzheimer disease, angiogenesis, Notch-, TGF[beta]- and VEGF-signalling
pathways. Sixteen genes best discriminated preeclamptic from normal
placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia
showed 168 differentially expressed genes with oxidative stress,
inflammation, and endothelin signalling pathways mainly involved
in early-onset disease. Validation of the microarray results was
performed by RT-PCR, quantitative urine hCG measurement and placental
histopathologic examination. In summary, placental gene expression
is altered in preeclampsia and we provide a comprehensive list of
the differentially expressed genes. Placental gene expression is
different between early- and late-onset preeclampsia, suggesting
differences in pathophysiology.},
issn = {0143-4004},
keywords = {Gene expression, Microarrays, Placenta, Severe preeclampsia},
url = {http://www.sciencedirect.com/science/article/B6WPD-4VPKPYG-2/2/af5aa427258262cf2d7dfd1b142ae4f4}
}
@ARTICLE{Sitras2009a,
author = {Sitras, Vasilis and Paulssen, Ruth and Leirvik, Jorn and Vartun,
Ase and Acharya, Ganesh},
title = {Placental Gene Expression Profile in Intrauterine Growth Restriction
Due to Placental Insufficiency},
journal = {Reproductive Sciences},
year = {2009},
volume = {16},
pages = {701--711},
number = {7},
month = jul,
abstract = {We evaluated global placental gene expression in intrauterine growth
restriction (IUGR; n = 8) compared to normal pregnancies (n = 8)
and studied possible additional effect of preeclampsia. Placental
samples were collected from IUGR pregnancies due to placental insufficiency
ascertained by hemodynamic studies. Four IUGR pregnancies were associated
with preeclampsia. Gene expression profile was evaluated by 30k oligonucleotide
microarrays. Principal component analysis (PCA) showed good separation
in terms of gene expression patterns between the groups. Pathway
analysis showed upregulation of inflammation mediated by chemokine
and cytokine signaling pathway in the IUGR placentas. Genes involved
in placental glucocorticoid metabolism were also differentially expressed.
None of the known imprinted placental genes were differentially expressed.
Subgroup analysis between IUGR placentas with and without preeclampsia
showed few (n = 27) differentially expressed genes. In conclusion,
IUGR due to placental insufficiency appears to alter placental glucocorticoid
metabolism, upregulates inflammatory response in placenta, and shares
common pathogenic mechanisms with severe early-onset preeclampsia.},
url = {http://rsx.sagepub.com/cgi/content/abstract/16/7/701}
}
@ARTICLE{Sitzmann2010,
author = {Sitzmann, Brandon D. and Lemos, Dario R. and Ottinger, Mary Ann and
Urbanski, Henryk F.},
title = {Effects of age on clock gene expression in the rhesus macaque pituitary
gland},
journal = {Neurobiol Aging},
year = {2010},
volume = {31},
pages = {696--705},
number = {4},
month = apr,
abstract = {Recent studies have shown that circadian clock genes are expressed
in various peripheral tissues, raising the possibility that multiple
clocks regulate circadian physiology. To study clock gene expression
in the rhesus macaque pituitary gland we used gene microarray data
and found that the pituitary glands of young and old adult males
express several components of the circadian clock (Per1, Per2, Cry1,
Bmal1, Clock, Rev-erbα and Csnk1ɛ). Semi-quantitative reverse-transcription
polymerase chain reaction (sqRT-PCR) confirmed the presence of these
core-clock genes and detected significant age-related differences
in the expression of Per2. sqRT-PCR also showed differential expression
of core-clock genes at two opposing time-points over the 24-h day,
with greater expression of Per2 and Bmal1 (P<0.05) at 1300h as compared
to 0100h. Immunohistochemistry revealed rhythmic expression of REV-ERBα
in the pituitary glands of female macaques. These data provide evidence
that the rhesus macaque pituitary gland expresses core-clock genes
and their associated protein products in a 24-h rhythmic pattern,
and that their expression is moderately impacted by aging processes.},
issn = {0197-4580},
keywords = {Circadian, Age, Pituitary, Rhesus macaque},
publisher = {Elsevier},
refid = {S0197-4580(08)00184-X},
url = {http://linkinghub.elsevier.com/retrieve/pii/S019745800800184X?showall=true}
}
@ARTICLE{Sivagnanasundaram2007,
author = {Sivagnanasundaram, Sinthuja and Fletcher, Danielle and Hubank, Mike
and Illingworth, Elizabeth and Skuse, David and Scambler, Peter},
title = {Differential gene expression in the hippocampus of the Df1/+ mice:
A model for 22q11.2 deletion syndrome and schizophrenia},
journal = {Brain Research},
year = {2007},
volume = {1139},
pages = {48--59},
month = mar,
abstract = {Genes and a 3-Mb deletion mapping to human chromosome 22q11.2 have
been implicated in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia.
The Df1 heterozygous (Df1/+) mice, a model for 22q11.2DS, display
specific deficits in hippocampus-dependent learning and memory and
impaired sensorimotor gating, abnormalities observed in patients
with schizophrenia and 22q11.2DS. In light of the analogous behavioral
abnormalities observed between the Df1/+ mice and 22q11.2DS and schizophrenia
respectively, particularly in association with the 22q11.2 deletion,
the Df1/+ mice are suitable for investigating the molecular changes
that may underlie the cognitive deficits and behavioral abnormalities
arising as a result of this deletion. Hence we applied microarray
technology to identify such molecular changes in the hippocampus
at the transcript level. Twelve genes mapping to the deleted region
were reliably identified as expressed in the hippocampus by microarray
analysis. 159 other differentially expressed genes/ESTs were also
identified. Thus far differential expression of fifteen of these
genes involved in signal transduction, synaptic plasticity, neuronal
differentiation, microtubule assembly and ubiquitin pathway relevant
to hippocampus mediated function have been confirmed by real-time
PCR. Of particular interest is the decreased expression (32%) of
calmodulin 1, encoding a calcium-dependent protein involved in the
calmodulin-calcineurin regulated pathway implicated in learning and
memory.},
issn = {0006-8993},
keywords = {Schizophrenia, Gene expression, Memory, Hippocampus, Microarray, 22q11.2
Deletion syndrome},
url = {http://www.sciencedirect.com/science/article/B6SYR-4MSPV5B-2/2/d5d943a29aba3b57fdd61920ed7a6e0c}
}
@ARTICLE{Sivaneson2011,
author = {Sivaneson, Melissa and Mikkelsen, Helga and Ventre, Isabelle and
Bordi, Christophe and Filloux, Alain},
title = {Two-component regulatory systems in Pseudomonas aeruginosa: an intricate
network mediating fimbrial and efflux pump gene expression},
journal = {Molecular Microbiology},
year = {2011},
volume = {79},
pages = {1353--1366},
number = {5},
abstract = {Summary Pseudomonas aeruginosa is responsible for chronic and acute
infections in humans. Chronic infections are associated with production
of fimbriae and the formation of a biofilm. The two-component system
Roc1 is named after its role in the regulation of cup genes, which
encode components of a machinery allowing assembly of fimbriae. A
non-characterized gene cluster, roc2, encodes components homologous
to the Roc1 system. We show that cross-regulation occurs between
the Roc1 and Roc2 signalling pathways. We demonstrate that the sensors
RocS2 and RocS1 converge on the response regulator RocA1 to control
cupC gene expression. This control is independent of the response
regulator RocA2. Instead, we show that these sensors act via the
RocA2 response regulator to repress the mexAB-oprM genes. These genes
encode a multidrug efflux pump and are upregulated in the rocA2 mutant,
which is less susceptible to antibiotics. It has been reported that
in cystic fibrosis lungs, in which P. aeruginosa adopts the biofilm
lifestyle, most isolates have an inactive MexAB-OprM pump. The concomitant
RocS2-dependent upregulation of cupC genes (biofilm formation) and
downregulation of mexAB-oprM genes (antibiotic resistance) is in
agreement with this observation. It suggests that the Roc systems
may sense the environment in the cystic fibrosis lung.},
doi = {10.1111/j.1365-2958.2010.07527.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07527.x}
}
@ARTICLE{Sivapalaratnam2011,
author = {Sivapalaratnam, Suthesh and Farrugia, Rosienne and Nieuwdorp, Max
and Langford, Cordelia and van Beem, Rachel and Maiwald, Stephanie
and Zwaginga, Jaap and Gusnanto, Arief and Watkins, Nicholas and
Trip, Mieke and Ouwehand, Willem},
title = {Identification of candidate genes linking systemic inflammation to
atherosclerosis; results of a human in vivo LPS infusion study},
journal = {BMC Medical Genomics},
year = {2011},
volume = {4},
pages = {64},
number = {1},
abstract = {BACKGROUND:It is widely accepted that atherosclerosis and inflammation
are intimately linked. Monocytes play a key role in both of these
processes and we hypothesized that activation of inflammatory pathways
in monocytes would lead to, among others, proatherogenic changes
in the monocyte transcriptome. Such differentially expressed genes
in circulating monocytes would be strong candidates for further investigation
in disease association studies.METHODS:Endotoxin, lipopolysaccharide
(LPS), or saline control was infused in healthy volunteers. Monocyte
RNA was isolated, processed and hybridized to Hver 2.1.1 spotted
cDNA microarrays. Differential expression of key genes was confirmed
by RT-PCR and results were compared to in vitro data obtained by
our group to identify candidate genes.RESULTS:All subjects who received
LPS experienced the anticipated clinical response indicating successful
stimulation. One hour after LPS infusion, 11 genes were identified
as being differentially expressed; 1 down regulated and 10 up regulated.
Four hours after LPS infusion, 28 genes were identified as being
differentially expressed; 3 being down regulated and 25 up regulated.
No genes were significantly differentially expressed following saline
infusion. Comparison with results obtained in in vitro experiments
lead to the identification of 6 strong candidate genes (BATF, BID,
C3aR1, IL1RN, SEC61B and SLC43A3)CONCLUSION:In vivo endotoxin exposure
of healthy individuals resulted in the identification of several
candidate genes through which systemic inflammation links to atherosclerosis.},
doi = {10.1186/1755-8794-4-64},
issn = {1755-8794},
pubmedid = {21827714},
url = {http://www.biomedcentral.com/1755-8794/4/64}
}
@ARTICLE{Sjoelinder2004,
author = {Sjölinder, Mikael and Uhlmann, Jörg and Ponstingl, Herwig},
title = {Characterisation of an evolutionary conserved protein interacting
with the putative guanine nucleotide exchange factor DelGEF and modulating
secretion},
journal = {Experimental Cell Research},
year = {2004},
volume = {294},
pages = {68--76},
number = {1},
month = mar,
abstract = {A human cDNA library was screened for proteins interacting with the
deafness locus putative guanine nucleotide exchange factor (DelGEF)
using a yeast two-hybrid system. A protein with a predicted size
of 9 kDa was identified as a binding partner, this protein was designated
DelGEF interacting protein 1 (DelGIP1). The interaction between DelGEF
and DelGIP1 was verified by co-immunoprecipitation of a DelGEF-DelGIP1
complex from cell lysates. Highly conserved homologues of DelGIP1
were identified in higher and lower eukaryotes by database searching.
The human DelGIP1 gene is ubiquitously expressed as judged by human
multiple tissue Northern blot analysis. DelGEF was recently shown
to interact with Sec5, a protein involved in secretion, and to regulate
secretion of proteoglycans. Downregulation of endogenous DelGIP1
in HeLa cells induced increased extracellular secretion of proteoglycans
indicating a possible role for DelGIP1 in the secretion process.},
issn = {0014-4827},
keywords = {DelGEF, DelGIP1, Yeast two-hybrid, Secretion, Proteoglycan},
url = {http://www.sciencedirect.com/science/article/B6WFC-4B6KFB0-3/2/971a06f537f392ad2d1e7f9c3e763519}
}
@ARTICLE{Sjoelinder2002,
author = {Sjölinder, Mikael and Uhlmann, Jörg and Ponstingl, Herwig},
title = {DelGEF, a homologue of the Ran guanine nucleotide exchange factor
RanGEF, binds to the exocyst component Sec5 and modulates secretion},
journal = {FEBS Letters},
year = {2002},
volume = {532},
pages = {211--215},
number = {1-2},
month = dec,
abstract = {In order to identify the function of deafness locus putative guanine
nucleotide exchange factor (DelGEF), a protein homologous to the
nucleotide exchange factor for the small GTPase Ran, a cDNA library
was screened for interacting proteins using a yeast two-hybrid system.
The human homologue of Sec5, a protein involved in vesicle transport
and secretion, was identified as a binding partner. The interaction
between DelGEF and Sec5 was found to be dependent on Mg2+ and stimulated
by guanosine triphosphate (GTP) or deoxycytidine triphosphate (dCTP).
Downregulation of endogenous DelGEF in HeLa cells induced increased
extracellular secretion of proteoglycans indicating a possible role
for DelGEF in the secretion process.},
issn = {0014-5793},
keywords = {Deafness locus putative guanine nucleotide exchange factor, Sec5,
Exocyst, Yeast two-hybrid, Deoxycytidine triphosphate, Guanosine
triphosphate},
url = {http://www.sciencedirect.com/science/article/B6T36-4772S3F-2/2/1b2ba2b8f947ee8f7e2e5454d5087528}
}
@ARTICLE{Sjoestrand2006,
author = {Sjöstrand, Christina and Duvefelt, Kristina and Steinberg, Anna and
Remahl, Ingela Nilsson and Waldenlind, Elisabet and Hillert, Jan},
title = {Gene Expression Profiling in Cluster Headache: A Pilot Microarray
Study},
journal = {Headache: The Journal of Head and Face Pain},
year = {2006},
volume = {46},
pages = {1518--1534},
number = {10},
abstract = {Background.—Cluster headache (CH) is a primary neurovascular headache
disorder characterized by attacks of excruciating pain accompanied
by ipsilateral autonomic symptoms. CH pathophysiology is presumed
to involve an activation of hypothalamic and trigeminovascular systems,
but inflammation and immunological mechanisms have also been hypothesized
to be of importance. Objective.—To identify differentially expressed
genes during different clinical phases of CH, assuming that changes
of pathophysiological importance would also be seen in peripheral
venous blood. Methods.—Blood samples were drawn at 3 consecutive
occasions from 3 episodic CH patients: during attacks, between attacks
and in remission, and at 1 occasion from 3 matched controls. Global
gene expression was analyzed with microarray tehnology using the
Affymetrix Human Genome U133 2.0 Plus GeneChip® Set, covering more
than 54,000 gene transcripts, corresponding to almost 22,000 genes.
Quantitative RT-PCR on S100P gene expression was analyzed in 6 patients
and 14 controls. Results.—Overall, quite small differences were
seen intraindividually and large differences interindividually. However,
pairwise comparisons of signal values showed upregulation of several
S100 calcium binding proteins; S100A8 (calgranulin A), S100A12 (calgranulin
C), and S100P during active phase of the disease compared to remission.
Also, annexin A3 (calcium-binding) and ICAM3 showed upregulation.
BIRC1 (neuronal apoptosis inhibitory protein), CREB5, HLA-DQA1, and
HLA-DQB1 were upregulated in patients compared to controls. The upregulation
of S100P during attack versus remission was confirmed by quantitative
RT-PCR analysis. Conclusions.—The S100A8 and S100A12 proteins are
considered markers of non-infectious inflammatory disease, while
the function of S100P is still largely unknown. Furthermore, upregulation
of HLA-DQ genes in CH patients may also indicate an inflammatory
response. Upregulation of these pro-inflammatory genes during the
active phase of CH has not formerly been reported. Data from this
pilot microarray study provide a basis for further studies in CH.},
issn = {1526-4610},
keywords = {cluster headache, pathophysiology, gene expression, inflammation,
S100, HLA},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1526-4610.2006.00611.x}
}
@ARTICLE{Skaggs2010,
author = {Skaggs, Brian J. and Hahn, Bevra H. and Sahakian, Lori and Grossman,
Jennifer and McMahon, Maureen},
title = {Dysfunctional, pro-inflammatory HDL directly upregulates monocyte
PDGFR[beta], chemotaxis and TNF[alpha] production},
journal = {Clinical Immunology},
year = {2010},
volume = {137},
pages = {147--156},
number = {1},
month = oct,
abstract = {Accelerated atherosclerosis is a major co-morbid condition in autoimmune
diseases. Monocytes are the main immune cell involved in atherosclerosis
initiation. We hypothesized that dysfunctional, pro-inflammatory
HDL (piHDL), which occurs in approximately half of SLE patients,
might directly influence monocyte gene expression and function. SLE
subjects were stratified into three groups: 1) carotid artery plaque+piHDL+, 2)
plaque-piHDL+, and 3) plaque-piHDL- (n = 18/group). PDGFR[beta] was
upregulated in primary monocytes from plaque+piHDL+ patients and
in THP-1 cells acutely treated in vitro with piHDL compared to normal
HDL. THP-1 chemotaxis was enhanced after treatment with piHDL versus
normal HDL. Abnormal migration was restored to normal levels by treatment
with imatinib or an apoJ mimetic peptide. Increased piHDL-mediated
TNF[alpha] protein levels were reduced with both inhibitors. Dysfunctional
piHDL directly influences expression of a small number of transcripts
and proteins, and piHDL inhibition through reducing piHDL oxidation
or blocking PDGFR[beta] kinase activity restored normal monocyte
chemotaxis.},
issn = {1521-6616},
keywords = {High-density lipoproteins, Monocyte, PDGFR[beta], Atherosclerosis,
Systemic lupus erythematosus},
url = {http://www.sciencedirect.com/science/article/B6WCJ-50J3D69-1/2/61c3de779eadb7b80fdb06eb753f48f2}
}
@ARTICLE{Skak2009,
author = {Skak, Kresten and Søndergaard, Henrik and Frederiksen, Klaus Stensgaard
and Ehrnrooth, Eva},
title = {In vivo antitumor efficacy of interleukin-21 in combination with
chemotherapeutics},
journal = {Cytokine},
year = {2009},
volume = {48},
pages = {231--238},
number = {3},
month = dec,
abstract = {Interleukin-21 (IL-21) is a class I cytokine with antitumor properties
due to enhanced proliferation and effector function of CD8+ T cells
and natural killer (NK) cells. Here we have explored the magnitude
and time-course of cytostatics-induced lymphopenia in mice and investigated
whether treatment with cytostatics influences the antitumor effect
of IL-21 in mouse tumor models. We show that pegylated liposomal
doxorubicin (PLD), irinotecan and oxaliplatin induced transient lymphopenia,
whereas 5-fluorouracil (5-FU) transiently increased lymphocyte counts.
B cells were more sensitive than T cells towards irinotecan and oxaliplatin.
Additive antitumor effects were observed after combining IL-21 with
PLD, oxaliplatin and to less extent 5-FU but not irinotecan, and
larger effect was observed when IL-21 administration was postponed
relative to chemotherapy, suggesting that these agents may transiently
impair immune function. However, the chemotherapies did not significantly
alter the levels of circulating regulatory T cells and only marginally
affected the ability of CD8+ T cells to respond to IL-21 measured
as increased granzyme B mRNA. Our results show that IL-21 therapy
can be successfully combined with agents from different chemotherapeutic
drug classes, i.e. topoisomerase II inhibitors (PLD), anti-metabolites
(5-FU) and platinum analogs (oxaliplatin) provided that IL-21 therapy
is delayed relative to chemotherapy.},
issn = {1043-4666},
keywords = {Immunotherapy, Cytokines, Chemotherapy, In vivo models},
url = {http://www.sciencedirect.com/science/article/B6WDF-4X30C4T-1/2/578a03deac15e9bc729b7f6b1b4a7b1d}
}
@ARTICLE{Skawran2009,
author = {Skawran, Britta and Dierich, Martin and Steinemann, Doris and Hohlfeld,
Jens and Haverich, Axel and Schlegelberger, Brigitte and Welte, Tobias
and von Neuhoff, Nils},
title = {Bronchial epithelial cells as a new source for differential transcriptome
analysis after lung transplantation},
journal = {European Journal of Cardio-Thoracic Surgery},
year = {2009},
volume = {36},
pages = {715--721},
number = {4},
month = oct,
abstract = {Objective: The early diagnosis of chronic organ rejection after lung
transplantation (LTx) is currently hampered by the lack of reliable
diagnostic markers. The present study aims to establish the procedure
of gene expression profiling in bronchial epithelial cells for the
identification of candidate genes that might prove useful in the
early diagnosis. Methods: Twenty-three patients who underwent lung
transplantations were investigated at a time point when no clinical
signs of bronchiolitis obliterans syndrome (BOS) were apparent. Bronchial
epithelial cells were obtained by bronchial brushing. Gene expression
profiles were determined using a human whole-genome cDNA microarray
(Stanford Faculty, Stanford, CA, USA). Results: Unsupervised hierarchical
cluster analysis revealed that the samples from LTx patients can
be clearly distinguished from the comparison group. We also found
that the samples from LTx patients with the same underlying disease
do not form major clusters of gene expression pattern. Using biostatistical
analysis, [`]haemoglobin beta', expressed by alveolar type II and
Clara cells, and CD99, involved in inflammatory processes, were identified
comparing lung transplantation and comparison group. Conclusions:
Thus, global expression analyses of bronchial epithelial cells might
be a new approach to identify diagnostic markers, especially if patients
with LTx are monitored sequentially and if patients with and without
BOS are compared.},
issn = {1010-7940},
keywords = {Bronchial epithelial cells, Gene expression profiling, Microarray
analysis},
url = {http://www.sciencedirect.com/science/article/B6T35-4WHDHTK-1/2/98c8deb500758aaf4a3e9b816b37655b}
}
@ARTICLE{Skazik2008,
author = {Skazik, Claudia and Heise, Ruth and Bostanci, Öznur and Paul, Nora
and Denecke, Bernd and Joussen, Sylvia and Kiehl, Klaudia and Merk,
Hans F. and Zwadlo-Klarwasser, Gabriele and Baron, Jens Malte},
title = {Differential expression of influx and efflux transport proteins in
human antigen presenting cells},
journal = {Experimental Dermatology},
year = {2008},
volume = {17},
pages = {739--747},
number = {9},
abstract = {Abstract:  Human macrophages (MΦ) express cytochrome P450 enzymes
verifying their capacity to metabolize a variety of endogenous and
exogenous substances. Here we analysed the mRNA and protein expression
of transport proteins involved in the uptake or export of drugs,
hormones and arachidonic acid metabolites in dendritic cells (DC)
and MΦ compared to their precursors – blood monocytes – using
cDNA microarray, RT-PCR, Western-blot and immunostaining techniques.
The transport proteins studied included members of the solute carrier
organic anion transporter family (SLCO) and the multidrug resistance
associated proteins (MRP) 1–6 belonging to the ATP-binding cassette
subfamily C (ABCC). We found that only mRNA for SLCO-2B1, -3A1, and
-4A1 were present in monocytes, MΦ and DC. Most interestingly the
expression of SLCO-2B1 was markedly enhanced in MΦ as compared to
monocytes and DC. The presence of mRNA for ABCC1, 3, 4, 5 and 6 in
all three cell types was demonstrated. On protein level ABCC1/MRP1
which has been identified as leukotriene C4 transporter was found
to be the most abundant transporter in MΦ and DC. Blocking the ABCC1/MRP1
activity with the specific inhibitor MK571 resulted in a phenotypic
change in DC but not in MΦ. Our data show that human blood monocytes
and monocyte derived MΦ as well as DC express a specific profile
of transporters involved in uptake and export of exogenous molecules
like allergens or drugs, but also of endogenous substances in particular
of inflammatory lipid mediators like leukotrienes and prostaglandins.},
issn = {1600-0625},
keywords = {ABCC-transporter, dendritic cells, macrophages, monocytes, SLCO-transporter},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0625.2008.00745.x}
}
@ARTICLE{Skelly2011,
author = {Skelly, Daniel A. and Johansson, Marnie and Madeoy, Jennifer and
Wakefield, Jon and Akey, Joshua M.},
title = {A powerful and flexible statistical framework for testing hypotheses
of allele-specific gene expression from RNA-seq data},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1728-1737},
number = {10},
abstract = {Variation in gene expression is thought to make a significant contribution
to phenotypic diversity among individuals within populations. Although
high-throughput cDNA sequencing offers a unique opportunity to delineate
the genome-wide architecture of regulatory variation, new statistical
methods need to be developed to capitalize on the wealth of information
contained in RNA-seq data sets. To this end, we developed a powerful
and flexible hierarchical Bayesian model that combines information
across loci to allow both global and locus-specific inferences about
allele-specific expression (ASE). We applied our methodology to a
large RNA-seq data set obtained in a diploid hybrid of two diverse
Saccharomyces cerevisiae strains, as well as to RNA-seq data from
an individual human genome. Our statistical framework accurately
quantifies levels of ASE with specified false-discovery rates, achieving
high reproducibility between independent sequencing platforms. We
pinpoint loci that show unusual and biologically interesting patterns
of ASE, including allele-specific alternative splicing and transcription
termination sites. Our methodology provides a rigorous, quantitative,
and high-resolution tool for profiling ASE across whole genomes.},
doi = {10.1101/gr.119784.110},
eprint = {http://genome.cshlp.org/cgi/reprint/21/10/1728.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/10/1728}
}
@ARTICLE{Skelton2010,
author = {Skelton, T. Spencer and Tejpal, Neelam and Gong, Yongquan and Kloc,
Malgorzata and Ghobrial, Rafik M.},
title = {Downregulation of RhoA and changes in T cell cytoskeleton correlate
with the abrogation of allograft rejection},
journal = {Transplant Immunology},
year = {2010},
volume = {23},
pages = {185--193},
number = {4},
month = aug,
abstract = {Proper actin cytoskeleton architecture and dynamics are indispensable
for events in the immunological response such as T cell migration,
redistribution of T cell receptors, and interaction with antigen
presenting cells. Thus, T cell activation, downstream signaling events
and effector functions are all actin-dependent. Actin cytoskeleton
architecture and dynamics are regulated by proteins belonging to
the superfamily of small GTP-binding proteins, such as RhoA GTPase.
We previously showed that the administration of an MHC class I allochimeric
molecule [[alpha]1h1/u]-RT1.Aa, which contains donor-type (Wistar
Furth, WF; RT1u) immunogenic epitopes displayed on recipient-type
(ACI, RT1a) sequences, to the ACI recipient of heterotopic WF heart
resulted in the restriction of the TCR repertoire, inhibition of
T cell infiltration into the heterotopic cardiac allografts, abrogation
of acute and chronic rejection, and induction of indefinite survival
of the allograft. Here we show that the allochimeric molecule treatment
caused downregulation of RhoA GTPase in T cells. This resulted in
dramatic changes in the distribution of actin and the actin-binding
protein, Hip55, in these cells, which in turn, inhibited T cell infiltration
into the graft. This indicates that the immunosuppressive activity
of the allochimeric molecule is achieved via downregulation of the
RhoA pathway and disruption of the proper organization of T cell
actin cytoskeleton to inhibit T cell functions such as motility and/or
TCR signaling events.},
issn = {0966-3274},
keywords = {T cell, Actin, RhoA, Hip55},
url = {http://www.sciencedirect.com/science/article/B6W6V-50G695X-1/2/35580decab9175cf2a01e6d2621f1931}
}
@ARTICLE{Skern-Mauritzen2009,
author = {Skern-Mauritzen, Rasmus and Frost, Petter and Dalvin, Sussie and
Kvamme, Bjørn and Sommerset, Ingunn and Nilsen, Frank},
title = {A trypsin-like protease with apparent dual function in early Lepeophtheirus
salmonis (Krøyer) development},
journal = {BMC Molecular Biology},
year = {2009},
volume = {10},
pages = {44},
number = {1},
abstract = {BACKGROUND:Trypsin-like serine proteases are involved in a large number
of processes including digestive degradation, regulation of developmental
processes, yolk degradation and yolk degradome activation. Trypsin
like peptidases considered to be involved in digestion have been
characterized in Lepeophtheirus salmonis. During these studies a
trypsin-like peptidase which differed in a number of traits were
identified.RESULTS:An intronless trypsin-like serine peptidase (LsTryp10)
from L., salmonis was identified and characterized. LsTryp10 mRNA
is evenly distributed in the ovaries and oocytes, but is located
along the ova periphery. LsTryp10 protein is deposited in the oocytes
and all embryonic cells. LsTryp10 mRNA translation and concurrent
degradation after fertilization was found in the embryos demonstrating
that LsTryp10 protein is produced both by the embryo and maternally.
The results furthermore indicate that LsTryp10 protein of maternal
origin has a distribution pattern different to that of embryonic
origin.CONCLUSION:Based on present data and previous studies of peptidases
in oocytes and embryos, we hypothesize that maternally deposited
LsTryp10 protein is involved in regulation of the yolk degradome.
The function of LsTryp10 produced by the embryonic cells remains
unknown. To our knowledge a similar expression pattern has not previously
been reported for any protease.},
doi = {10.1186/1471-2199-10-44},
issn = {1471-2199},
pubmedid = {19439101},
url = {http://www.biomedcentral.com/1471-2199/10/44}
}
@ARTICLE{Skern-Mauritzen2007,
author = {Skern-Mauritzen, Rasmus and Frost, Petter and Hamre, Lars A. and
Kongshaug, Heidi and Nilsen, Frank},
title = {Molecular characterization and classification of a clip domain containing
peptidase from the ectoparasite Lepeophtheirus salmonis (Copepoda,
Crustacea)},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2007},
volume = {146},
pages = {289--298},
number = {2},
month = feb,
abstract = {Clip domain containing serine peptidases (CSPs) include one or more
N-terminal clip domain(s) and a C-terminal serine peptidase domain
that shares traits with both chymotrypsin and trypsin. CSPs are found
in arthropods and are involved in embryonic patterning, immune responses
and blood clotting. Among crustaceans only one CSP, which activates
prophenoloxidase in crayfish, have previously been reported. We here
present LsCSP1, the first CSP found in copepods. LsCSP1 is expressed
in the subcuticular tissue and the transcription appears to be upregulated
during development. In conjunction with previous studies of CSPs,
this study suggests that LsCSP1 may play a role in the immune responses
of L. salmonis. Phylogenetic and structural analyses indicate that
the CSPs and catalytically inactive CSP homologs (CSPHs) constitute
a monophyletic lineage.},
issn = {1096-4959},
keywords = {Easter, Immune system, Phylogeny, Prophenoloxidase, Proteolytic cascade,
Salmon louse},
url = {http://www.sciencedirect.com/science/article/B6T2R-4MDWY3K-1/2/bbb7a8376ee91d38a938c6d732a86251}
}
@ARTICLE{Skierka2010,
author = {Skierka, Jennifer M. and O'Kane, Dennis J.},
title = {UDP-Glucuronosyltransferase 1A1 and the Glucuronidation in Oncology
Applications and Hyperbilirubinemia},
journal = {Molecular Diagnostics},
year = {2010},
volume = {NA},
pages = {409--419},
address = {San Diego},
booktitle = {Molecular Diagnostics},
editor = {Contributors and Grody, Wayne W. and M.D. and Ph.D. and Nakamura,
Robert M. and M.D. and Strom, Charles M. and M.D. and Ph.D. and Kiechle,
Frederick L. and MD and PhD.},
issn = {978-0-12-369428-7},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B9FBB-4Y59TYN-11/2/dc4bbd9fbcacbe6538171f333e74a302}
}
@ARTICLE{Skipor2010,
author = {Skipor, J. and Misztal, T. and Kaczmarek, M.M.},
title = {Independent changes of thyroid hormones in blood plasma and cerebrospinal
fluid after melatonin treatment in ewes},
journal = {Theriogenology},
year = {2010},
volume = {74},
pages = {236--245},
number = {2},
month = jul,
abstract = {The authors measured the effects of exogenous melatonin treatment
on the concentrations of total (T) and free (f) fractions of thyroxine
(T4) and triiodothyronine (T3) in cerebrospinal fluid (CSF) and blood
plasma as well as the expression of their binding/transporter protein,
transthyretin (TTR), in the choroid plexus of ewes from May to August.
Melatonin implantation in May and July mainly prevented the decrease
in plasma for fT3 and TT3 exhibited in untreated group, and induced
a limited decrease in TT4 in June. By contrast, melatonin implantation
prevented the decrease in CSF fT3 observed in the untreated group.
No effect of melatonin was found on the expression of TTR mRNA in
the choroid plexus There were a correlations between blood fT4 and
CSF TT4 concentrations in both control and melatonin treated group
(r2−0.4; P < 0.01 vs. r2−0.14; P < 0.05), as well as between
blood fT3 and CSF TT3 concentrations but only in the melatonin-treated
group (r2−0.26; P < 0.02). We conclude that T3, the active form
of the hormone within the brain, is regulated by melatonin independently
of the peripheral changes within the blood. The lack of correlation
between plasma fT3 and CSF TT3 in the control group suggests that
an increase in local T3 conversion could contribute as an additional
source of T3 in the CSF during the period of increasing day length.
These data seem to confirm a local nature for recently discovered
connections between the pineal melatonin signal and thyroid-dependent
seasonal biology in mammals.},
issn = {0093-691X},
keywords = {Transthyretin, Thyroxine, Triiodothyronine, Melatonin, Cerebrospinal
fluid, Choroid plexus, Ewe},
publisher = {Elsevier},
refid = {S0093-691X(10)00100-7},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0093691X10001007?showall=true}
}
@ARTICLE{Skjaerven2011,
author = {Skjærven, Kaja H. and Olsvik, Pål A. and Finn, Roderick Nigel and
Holen, Elisabeth and Hamre, Kristin},
title = {Ontogenetic expression of maternal and zygotic genes in Atlantic
cod embryos under ambient and thermally stressed conditions},
journal = {Comparative Biochemistry and Physiology - Part A: Molecular \& Integrative
Physiology},
year = {2011},
volume = {159},
pages = {196--205},
number = {2},
month = jun,
abstract = {The embryonic stages of Atlantic cod (Gadus morhua) are especially
sensitive to incubation temperature. The purpose of the present study
was to follow the ontogenetic expression of selected genes of maternal
(pou2 and nanog) and zygotic origin (hsp70, hsp90[alpha] and stip1),
in Atlantic cod embryos under ambient and thermally stressed conditions.
The study also investigated how reference genes can be applied to
studies on embryonic development, when maternal genes are degraded
and the zygotic transcription stabilizes. Three batches of eggs were
reared and gene expression profiles from the reference and target
genes were determined. The embryos were reared at ambient 6 °C, and
10 °C for continuous long-term and acute short-term heat exposure.
Both pou2 and nanog showed reduced expression whereas the zygotic
and reference genes showed increased expression until stabilizing
at gastrulation, when a normalized ontogenetic expression profile
of target genes could be generated. pou2 and nanog were not affected
by thermal stress. In contrast, hsp70 and hsp90[alpha] were upregulated
after short-term heat exposure at the early blastula (hsp70 only),
late blastula, 50% epiboly and 90% epiboly stages (hsp90[alpha] only).
Long-term heat exposure of Atlantic cod embryos upregulated both
hsp70 (90% epiboly) and hsp90[alpha] (90% epiboly and 20-somites).
The results suggest that a cellular defense mechanism is activated
even in the earliest stages of embryonic development, a period critical
to developmental temperature.},
issn = {1095-6433},
keywords = {Atlantic cod embryos, pou2, nanog, hsp70, hsp90[alpha], Reference
genes},
url = {http://www.sciencedirect.com/science/article/pii/S1095643311000596}
}
@ARTICLE{Skjoelberg2009,
author = {Skjølberg, Henriette and Fensgård, Øyvind and Nilsen, Hilde and Grallert,
Beáta and Boye, Erik},
title = {Global transcriptional response after exposure of fission yeast cells
to ultraviolet light},
journal = {BMC Cell Biology},
year = {2009},
volume = {10},
pages = {87},
number = {1},
abstract = {BACKGROUND:In many cell types, including the fission yeast Schizosaccharomyces
pombe, a set of checkpoints are induced by perturbations of the cell
cycle or by DNA damage. Many of the checkpoint responses include
a substantial change of the transcriptional pattern. As part of characterising
a novel G1/S checkpoint in fission yeast we have investigated whether
a transcriptional response is induced after irradiation with ultraviolet
light.RESULTS:Microarray analyses were used to measure the global
transcription levels of all open reading frames of fission yeast
after 254 nm ultraviolet irradiation, which is known to induce a
G1/S checkpoint. We discovered a surprisingly weak transcriptional
response, which is quite unlike the marked changes detected after
some other types of treatment and in several other checkpoints. Interestingly,
the alterations in gene expression after ultraviolet irradiation
were not similar to those observed after ionising radiation or oxidative
stress. Pathway analysis suggests that there is little systematic
transcriptional response to the irradiation by ultraviolet light,
but a marked, coordinated transcriptional response was noted on progression
of the cells from G1 to S phase.CONCLUSION:There is little response
in fission yeast to ultraviolet light at the transcriptional level.
Amongst the genes induced or repressed after ultraviolet irradiation
we found none that are likely to be involved in the G1/S checkpoint
mechanism, suggesting that the checkpoint is not dependent upon transcriptional
regulation.},
doi = {10.1186/1471-2121-10-87},
issn = {1471-2121},
pubmedid = {20015352},
url = {http://www.biomedcentral.com/1471-2121/10/87}
}
@ARTICLE{Skoglund2007,
author = {Skoglund, Anna and Bjorkholm, Britta and Nilsson, Christina and Andersson,
Anders F. and Jernberg, Cecilia and Schirwitz, Katja and Enroth,
Cristofer and Krabbe, Margareta and Engstrand, Lars},
title = {Functional Analysis of the M.HpyAIV DNA Methyltransferase of Helicobacter
pylori},
journal = {J. Bacteriol.},
year = {2007},
volume = {189},
pages = {8914--8921},
number = {24},
month = dec,
abstract = {A large number of genes encoding restriction-modification (R-M) systems
are found in the genome of the human pathogen Helicobacter pylori.
R-M genes comprise approximately 10% of the strain-specific genes,
but the relevance of having such an abundance of these genes is not
clear. The type II methyltransferase (MTase) M.HpyAIV, which recognizes
GANTC sites, was present in 60% of the H. pylori strains analyzed,
whereof 69% were resistant to restriction enzyme digestion, which
indicated the presence of an active MTase. H. pylori strains with
an inactive M.HpyAIV phenotype contained deletions in regions of
homopolymers within the gene, which resulted in premature translational
stops, suggesting that M.HpyAIV may be subjected to phase variation
by a slipped-strand mechanism. An M.HpyAIV gene mutant was constructed
by insertional mutagenesis, and this mutant showed the same viability
and ability to induce interleukin-8 in epithelial cells as the wild
type in vitro but had, as expected, lost the ability to protect its
self-DNA from digestion by a cognate restriction enzyme. The M.HpyAIV
from H. pylori strain 26695 was overexpressed in Escherichia coli,
and the protein was purified and was able to bind to DNA and protect
GANTC sites from digestion in vitro. A bioinformatic analysis of
the number of GANTC sites located in predicted regulatory regions
of H. pylori strains 26695 and J99 resulted in a number of candidate
genes. katA, a selected candidate gene, was further analyzed by quantitative
real-time reverse transcription-PCR and shown to be significantly
down-regulated in the M.HpyAIV gene mutant compared to the wild-type
strain. This demonstrates the influence of M.HpyAIV methylation in
gene expression.},
url = {http://jb.asm.org/cgi/content/abstract/189/24/8914}
}
@ARTICLE{Skolness2011,
author = {Skolness, Sarah Y. and Durhan, Elizabeth J. and Garcia-Reyero, Natalia
and Jensen, Kathleen M. and Kahl, Michael D. and Makynen, Elizabeth
A. and Martinovic-Weigelt, Dalma and Perkins, Edward and Villeneuve,
Daniel L. and Ankley, Gerald T.},
title = {Effects of a short-term exposure to the fungicide prochloraz on endocrine
function and gene expression in female fathead minnows (Pimephales
promelas)},
journal = {Aquatic Toxicology},
year = {2011},
volume = {103},
pages = {170--178},
number = {3-4},
month = jun,
abstract = {Prochloraz is a fungicide known to cause endocrine disruption through
effects on the hypothalamic-pituitary-gonadal (HPG) axis. To determine
the short-term impacts of prochloraz on gene expression and steroid
production, adult female fathead minnows (Pimephales promelas) were
exposed to the chemical (0 or 300 [mu]g/L) for a time-course of 6,
12 and 24 h. Consistent with inhibition of cytochrome P450 17[alpha]-hydroxylase/17,20-lyase
(CYP17) and aromatase (CYP19), known molecular targets of prochloraz,
plasma 17[beta]-estradiol (E2) was reduced within 6 h. Ex vivo E2
production was significantly reduced at all time-points, while ex
vivo testosterone (T) production remained unchanged. Consistent with
the decrease in E2 levels, plasma concentrations of the estrogen-responsive
protein vitellogenin were significantly reduced at 24 h. Genes coding
for CYP19, CYP17, and steroidogenic acute regulatory protein were
up-regulated in a compensatory manner in ovaries of the prochloraz-treated
fish. In addition to targeted quantitative real-time polymerase chain
reaction analyses, a 15k feature fathead minnow microarray was used
to determine gene expression profiles in ovaries. From time-point
to time-point, the microarray results showed a relatively rapid change
in the differentially expressed gene (DEG) profiles associated with
the chemical exposure. Functional analysis of the DEGs indicated
changes in expression of genes associated with cofactor and coenzyme
binding (GO:0048037 and 0050662), fatty acid binding (GO:0005504)
and organelle organization and biogenesis (GO:0006996). Overall,
the results from this study are consistent with compensation of the
fish HPG axis to inhibition of steroidogenesis by prochloraz, and
provide further insights into relatively rapid, system-wide, effects
of a model chemical stressor on fish.},
issn = {0166-445X},
keywords = {Estrogen, Fish, Microarray, Vitellogenin, Endocrine disruption, Aromatase},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X11000531}
}
@ARTICLE{Skopec2007,
author = {Skopec, Michele M. and Haley, Shannon and Dearing, M. Denise},
title = {Differential hepatic gene expression of a dietary specialist (Neotoma
stephensi) and generalist (Neotoma albigula) in response to juniper
(Juniperus monosperma) ingestion},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2007},
volume = {2},
pages = {34--43},
number = {1},
month = mar,
abstract = {Dietary specialization is thought to be rare in mammalian herbivores
because of limitations of their detoxification system in processing
large doses of a single type of plant secondary compound (PSC). Therefore,
in order to specialize on a single species of plant, mammalian herbivores
must have a highly efficient detoxification system for the particular
types of PSCs they ingest. Using microarray technology, we looked
at the expression of hepatic genes of a dietary specialist, Neotoma
stephensi, and a sympatric generalist, Neotoma albigula, in response
to diets containing different levels of one-seeded juniper (Juniperus
monosperma). We found large between species differences in gene expression,
as well as large within species differences when specialists fed
a low juniper diet (25% juniper) were compared to specialists fed
their ecologically relevant level of juniper (70% juniper). We also
tested the hypothesis that the specialist relies on less costly phase
I detoxification enzymes more than phase II compared to the generalist.
Although we found that the specialist had higher cumulative as well
as average expression of phase I versus phase II enzymes, the generalist
had a similar pattern of expression for phase I versus phase II enzymes.},
issn = {1744-117X},
keywords = {Detoxification, Herbivores, Neotoma, Gene expression, Microarray},
url = {http://www.sciencedirect.com/science/article/B7XM1-4MC81R7-1/2/a539cf512c4f5f6aa2bbe0ace1080107}
}
@ARTICLE{Skory2010,
author = {Skory, Christopher D. and Hector, Ronald E. and Gorsich, Steven W.
and Rich, Joseph O.},
title = {Analysis of a functional lactate permease in the fungus Rhizopus},
journal = {Enzyme and Microbial Technology},
year = {2010},
volume = {46},
pages = {43--50},
number = {1},
month = jan,
abstract = {The fungus Rhizopus is frequently used for fermentative production
of lactic acid, but little is known about the mechanisms or proteins
for transporting this carboxylic acid. Since transport of the lactate
anion across the plasma membrane is critical to prevent acidification
of the cytoplasm, we evaluated the functionality of two lactate-proton
symport paralogs, LacA and LacB, from Rhizopus delemar. Both of these
proteins showed significant ancestral homology to bacterial lactate
permease with 46-50% identity to similar homologs from the genus
Burkholderia. Based on qPCR, the highest level of expression in Rhizopus
for the lacA gene was on complex medium containing pyruvate, while
lacB transcript was barely detected with all of the tested culture
conditions. A Saccharomyces cerevisiae jen1 deletion strain lacking
the ability to transport monocarboxylates was restored for growth
on lactate and pyruvate with the expression of LacA. Expression of
the LacB in this same strain did not confer the ability to grow on
either carbon source. LacA expression also allowed active transport
of L-[14C(U)]-lactate into yeast cells and this accumulation was
inhibited by the proton uncoupler carbonyl cyanide p-(trifluoromethoxy)
phenylhydrazone. Translation fusions with GFP showed that LacA accumulates
primarily in the plasma and vacuolar membrane, while LacB is dispersed
throughout the cytoplasm. These results indicate that the Rhizopus
LacA is a functional lactate symport that is probably involved in
uptake of pyruvate or lactate, while the physiological role of LacB
is unknown.},
issn = {0141-0229},
keywords = {Rhizopus, Lactate permease, Lactate symport},
url = {http://www.sciencedirect.com/science/article/B6TG1-4X3DMXC-1/2/e8647b75c1c99d7fa6791a03d2909292}
}
@ARTICLE{Skotheim2005,
author = {Skotheim, Rolf I. and Lind, Guro E. and Monni, Outi and Nesland,
Jahn M. and Abeler, Vera M. and Fossa, Sophie D. and Duale, Nur and
Brunborg, Gunnar and Kallioniemi, Olli and Andrews, Peter W. and
Lothe, Ragnhild A.},
title = {Differentiation of Human Embryonal Carcinomas In vitro and In vivo
Reveals Expression Profiles Relevant to Normal Development},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {5588--5598},
number = {13},
month = jul,
abstract = {Embryonal carcinoma is a histologic subgroup of testicular germ cell
tumors (TGCTs), and its cells may follow differentiation lineages
in a manner similar to early embryogenesis. To acquire new knowledge
about the transcriptional programs operating in this tumor development
model, we used 22k oligo DNA microarrays to analyze normal and neoplastic
tissue samples from human testis. Additionally, retinoic acid-induced
in vitro differentiation was studied in relevant cell lines. We identified
genes characterizing each of the known histologic subtypes, adding
up to a total set of 687 differentially expressed genes. Among these,
there was a significant overrepresentation of gene categories, such
as genomic imprinting and gene transcripts associated to embryonic
stem cells. Selection for genes highly expressed in the undifferentiated
embryonal carcinomas resulted in the identification of 58 genes,
including pluripotency markers, such as the homeobox genes NANOG
and POU5F1 (OCT3/4), as well as GAL, DPPA4, and NALP7. Interestingly,
abundant expression of several of the pluripotency genes was also
detected in precursor lesions and seminomas. By use of tissue microarrays
containing 510 clinical testicular samples, GAL and POU5F1 were up-regulated
in TGCT also at the protein level and hence validated as diagnostic
markers for undifferentiated tumor cells. The present study shows
the unique gene expression profiles of each histologic subtype of
TGCT from which we have identified deregulated components in selected
processes operating in normal development, such as WNT signaling
and DNA methylation.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/13/5588}
}
@ARTICLE{Skov2007,
author = {Skov, Vibe and Glintborg, Dorte and Knudsen, Steen and Jensen, Thomas
and Kruse, Torben A. and Tan, Qihua and Brusgaard, Klaus and Beck-Nielsen,
Henning and Hojlund, Kurt},
title = {Reduced Expression of Nuclear-Encoded Genes Involved in Mitochondrial
Oxidative Metabolism in Skeletal Muscle of Insulin-Resistant Women
With Polycystic Ovary Syndrome},
journal = {Diabetes},
year = {2007},
volume = {56},
pages = {2349--2355},
number = {9},
month = sep,
abstract = {Insulin resistance in skeletal muscle is a major risk factor for the
development of type 2 diabetes in women with polycystic ovary syndrome
(PCOS). In patients with type 2 diabetes, insulin resistance in skeletal
muscle is associated with abnormalities in insulin signaling, fatty
acid metabolism, and mitochondrial oxidative phosphorylation (OXPHOS).
In PCOS patients, the molecular mechanisms of insulin resistance
are, however, less well characterized. To identify biological pathways
of importance for the pathogenesis of insulin resistance in PCOS,
we compared gene expression in skeletal muscle of metabolically characterized
PCOS patients (n = 16) and healthy control subjects (n = 13) using
two different approaches for global pathway analysis: gene set enrichment
analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP
2.0). We demonstrate that impaired insulin-stimulated total, oxidative
and nonoxidative glucose disposal in PCOS patients are associated
with a consistent downregulation of OXPHOS gene expression using
GSEA and GenMAPP analysis. Quantitative real-time PCR analysis validated
these findings and showed that reduced levels of peroxisome proliferator-activated
receptor {gamma} coactivator {alpha} (PGC-1{alpha}) could play a
role in the downregulation of OXPHOS genes in PCOS. In these women
with PCOS, the decrease in OXPHOS gene expression in skeletal muscle
cannot be ascribed to obesity and diabetes. This supports the hypothesis
of an early association between insulin resistance and impaired mitochondrial
oxidative metabolism, which is, in part, mediated by reduced PGC-1{alpha}
levels. These abnormalities may contribute to the increased risk
of type 2 diabetes observed in women with PCOS.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/56/9/2349}
}
@ARTICLE{Skov2011,
author = {Skov, Vibe and Larsen, Thomas Stauffer and Thomassen, Mads and Riley,
Caroline Hasselbalch and Jensen, Morten K. and Bjerrum, Ole Weis
and Kruse, Torben A. and Hasselbalch, Hans Carl},
title = {Whole-blood transcriptional profiling of interferon-inducible genes
identifies highly upregulated IFI27 in primary myelofibrosis},
journal = {European Journal of Haematology},
year = {2011},
volume = {87},
pages = {54--60},
number = {1},
abstract = {Gene expression profiling studies have unraveled deregulation of several
genes that might be of pathogenetic importance for the development
and phenotype of the Philadelphia-negative chronic myeloproliferative
neoplasms. In the context of interferon-alpha2 as a promising therapeutic
agent, we focused upon the transcriptional profiling of interferon-associated
genes in patients with essential thrombocythemia (ET) (n = 19),
polycythemia vera (PV) (n = 41), and primary myelofibrosis (PMF)
(n = 9). Using whole-blood transcriptional profiling and accordingly
obtaining an integrated signature of genes expressed in several immune
cells (granulocytes, monocytes, B cells, T cells, platelets), we
have identified a number of interferon-associated genes to be significantly
deregulated but with a highly significant deregulation of interferon-inducible
gene 27 (IFI27) (ET, PV, and PMF, fold change 8, 16, and 30, respectively).
The striking deregulation of IFI genes may reflect a hyperstimulated
but insufficient immune system being most enhanced in patients with
advanced myelofibrosis, in whom the IFI27 gene displayed an exceedingly
high expression. The interferon signature may reflect primary myelofibrosis
as the burn-out phase of chronic inflammation which ultimately elicits
clonal evolution and expansion owing to an exaggerated but incompetent
antitumor immune response. Finally, IFI27 may be a novel biomarker
of disease activity and tumor burden in patients with CMPNs.},
doi = {10.1111/j.1600-0609.2011.01618.x},
issn = {1600-0609},
keywords = {interferon-induced genes, IFI27, essential thrombocythemia, polycythemia
vera, primary myelofibrosis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0609.2011.01618.x}
}
@ARTICLE{Skov2011a,
author = {Skov, Vibe and Larsen, Thomas Stauffer and Thomassen, Mads and Riley,
Caroline Hasselbalch and Jensen, Morten K and Bjerrum, Ole Weis and
Kruse, Torben A and Hasselbalch, Hans Carl},
title = {Whole Blood Transcriptional Profiling of Interferon-Inducible Genes
Identifies Highly Upregulated IFI27 in Primary Myelofibrosis},
journal = {European Journal of Haematology},
year = {2011},
pages = {no--no},
abstract = {Abstract Gene expression profiling studies have unravelled deregulation
of several genes which might be of pathogenetic importance for the
development and phenotype of the Philadelphia-negative chronic myeloproliferative
neoplasms. In the context of interferon-alpha2 as a promising therapeutic
agent we focused upon the transcriptional profiling of interferon-associated
genes in patients with ET (n =19), PV (n = 41), and PMF (n = 9).
Using whole blood transcriptional profiling and accordingly obtaining
an integrated signature of genes expressed in several immune cells
(granulocytes,monocytes, B-cells,,T-cells, platelets), we have identified
a number of interferon-associated genes to be significantly deregulated
but with a highly significant deregulation of interferon-inducible
gene 27 (IFI27) (ET, PV, and PMF, fold change 8, 16 and 30, respectively).
The striking deregulation of IFI genes may reflect a hyperstimulated
but insufficient immune system being most enhanced in patients with
advanced myelofibrosis, in whom the IFI27 gene displayed an exceedingly
high expression. The interferon signature may reflect primary myelofibrosis
as the burn-out phase of chronic inflammation which ultimatively
elicits clonal evolution and expansion due to an exaggerated but
incompetent anti-tumor immune response. Finally, IFI27 may be a novel
biomarker of disease activity and tumor burden in patients with CMPNs.},
doi = {10.1111/j.1600-0609.2011.01618.x},
issn = {1600-0609},
keywords = {Interferon-induced genes, IFI27, essential thrombocythemia, polycythemia
vera, primary myelofibrosis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0609.2011.01618.x}
}
@ARTICLE{Skovgaard2006,
author = {Skovgaard, Kerstin and Grell, Susanne Nedergaard and Heegaard, Peter
M.H. and Jungersen, Gregers and Pudrith, Chas B. and Coussens, Paul
M.},
title = {Differential expression of genes encoding CD30L and P-selectin in
cattle with Johne's disease: Progress toward a diagnostic gene expression
signature},
journal = {Veterinary Immunology and Immunopathology},
year = {2006},
volume = {112},
pages = {210--224},
number = {3-4},
month = aug,
abstract = {Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis),
the causative agent of paratuberculosis (paraTB) or Johne's disease
in ruminants, is a health problem for the global cattle industry
with significant economic losses related to decreased milk production
and reduced fertility. Commonly paraTB in cattle is diagnosed by
antibody detection by serum enzyme-linked immunosorbent assay (ELISA),
by detection of the pathogen by cultivation of individual faecal
samples, or by in vitro measurement of cell mediated immune responses
using the IFN-[gamma] test. There is an ongoing need for developing
new diagnostic approaches as all currently available diagnostic tests
for paraTB may fail to detect sub-clinical infection. We used cDNA
microarrays to simultaneously measure expression of over 1300 host
genes to help identify a subset of gene expression changes that might
provide a unique gene expression signature for paraTB infection.
In the present study, non-stimulated leukocytes isolated from 10
sub-clinical paraTB infected cows were examined for genes being expressed
at significantly different levels than in similar cells from control
cows with the same herd background. We included cattle (Holstein)
from two locations (Denmark and USA) for the microarray experiment.
Our results indicate that expression profiles of at least 52 genes
are different in leukocytes from M. paratuberculosis infected cattle
compared to control cattle. Gene expression differences were verified
by quantitative real-time reverse transcriptase polymerase chain
reactions (qRT-PCR) on the same group of cattle (Holstein) used for
the microarray experiment. In order to assess the generality of the
observed gene expression, a second and different group of cattle
(Jersey) was also examined using qRT-PCR. Out of the seven genes
selected for qRT-PCR, CD30 ligand (CD30L) and P-selectin were consistently
differentially expressed in freshly isolated leukocytes from paraTB
infected and control animals of both breeds of cattle. Although further
work is clearly needed to develop a more complete gene expression
signature specific for paraTB, our results demonstrate that a subset
of genes in leukocytes are consistently expressed at different levels,
depending upon M. paratuberculosis infection status.},
issn = {0165-2427},
keywords = {Paratuberculosis, Mycobacteria, Johne's disease, cDNA microarray,
Gene expression signature},
url = {http://www.sciencedirect.com/science/article/B6TD5-4JRVFPP-4/2/14a42833d2ebae68e30be1e1d9ee7ade}
}
@ARTICLE{Skovgaard2010,
author = {Skovgaard, Kerstin and Mortensen, Shila and Boye, Mette and Hedegaard,
Jakob and Heegaard, Peter M.H.},
title = {Hepatic gene expression changes in pigs experimentally infected with
the lung pathogen Actinobacillus pleuropneumoniae as analysed with
an innate immunity focused microarray},
journal = {Innate Immunity},
year = {2010},
volume = {16},
pages = {343--353},
number = {6},
month = dec,
abstract = {Knowledge on gene expression in the liver during respiratory infections
is limited although it is well-established that this organ is an
important site of synthesis of several systemic innate immune components
as response to infections. In the present study, the early transcriptional
hepatic response of genes associated with innate immune responses
was studied in pigs 14--18 h after intranasal inoculation with Actinobacillus
pleuropneumoniae, using innate immune focused microarrays and quantitative
real-time PCR (qPCR). The microarray analysis of liver tissue established
that 51 genes were differentially expressed. A large group of these
genes encoded proteins involved in the acute phase response, including
serum amyloid A, C-reactive protein, fibrinogen, haptoglobin and
tumor necrosis factor-{alpha} the expression of which were all found
to be up-regulated and glutathione S-transferase, transthyretin,
transferrin and albumin which were down-regulated. Additional genes
associated with innate immune responses were investigated using qPCR;
genes encoding interleukin-(IL-)1, IL-6, IL-8, lipopolysaccharide
binding protein, lactotransferrin, and PigMAP were up-regulated and
interferon 1{alpha}, {alpha}1-acid glycoprotein, mannan-binding lectin
A, surfactant protein D, and surfactant protein A1 were down-regulated
in the liver of infected animals. Down-regulation of {alpha}1-acid
glycoprotein during infection has not been described previously in
any species. These results confirm that the liver plays an important
role in initiating and orchestrating the innate immune response to
A. pleuropneumoniae infection.},
comment = {10.1177/1753425909342730},
url = {http://ini.sagepub.com/cgi/content/abstract/16/6/343}
}
@ARTICLE{Skovgaard2007,
author = {Skovgaard, Kerstin and Mortensen, Shila and Poulsen, Karin T. and
Angen, Øystein and Heegaard, Peter M.H.},
title = {Validation of putative reference genes for qRT-PCR normalization
in tissues and blood from pigs infected with Actinobacillus pleuropneumoniae},
journal = {Veterinary Immunology and Immunopathology},
year = {2007},
volume = {118},
pages = {140--146},
number = {1-2},
month = jul,
abstract = {The quantitative real-time reverse transcriptase polymerase chain
reaction (qRT-PCR) is a sensitive and very efficient technique for
quantification of gene expression. However, qRT-PCR relies on accurate
normalization of gene expression data, as RNA recovery and cDNA synthesis
efficiency might vary from sample to sample. In the present study,
six putative reference genes were validated for normalization of
gene expression in three different tissues and in white blood cells
from pigs experimentally infected with the common respiratory pathogen
Actinobacillus pleuropneumoniae. Two dedicated validation programs
(geNorm and Normfinder) were used to rank the six reference genes
from best to worst. qRT-PCR data for the proinflammatory cytokine
IL-6 was normalized using the proposed genes from geNorm and Normfinder
as well as the commonly used reference gene glyceraldehyde-3-phosphate
dehydrogenase (GAPDH). IL-6 expression was quantified in white blood
cells, liver, lymph nodes and tonsils from 10 infected pigs and 5
control pigs. After normalization using either geNorm or Normfinder
IL-6 was shown to be significantly up-regulated (P < 0.05) in all
of the tissues from infected animals compared to non-infected control
animals with a good agreement of expression differences between the
two programs. On the contrary, normalization of IL-6 expression data
from blood using GAPDH rendered the difference between infected and
non-infected groups non-significant, and resulted in significantly
different values compared to geNorm (P = 0.01). Based on these results,
we recommend to validate putative reference genes before normalization.},
issn = {0165-2427},
keywords = {Gene expression, Reference genes, geNorm, Normfinder, Porcine pleuropneumonia,
qRT-PCR},
url = {http://www.sciencedirect.com/science/article/B6TD5-4NMSRS3-2/2/c1e6c08d5fc2743537e0cda26630452e}
}
@ARTICLE{Skretting2009,
author = {Skretting, Grethe and Lien, Trude and Sandset, Per Morten and Iversen,
Nina},
title = {Expression of the V264M TFPI mutant in endothelial cell cultures
may involve mRNA stability},
journal = {Thrombosis Research},
year = {2009},
volume = {123},
pages = {851--855},
number = {6},
month = apr,
abstract = {Introduction Tissue factor (TF) pathway inhibitor (TFPI) is the endogenous
inhibitor regulating TF-induced blood coagulation. Several polymorphisms
have been identified in the TFPI gene and some of them have been
correlated with variations in plasma TFPI levels. The aim of the
present study was to characterize the TFPIV264M mutant in comparison
with the wild type protein (TFPIWT).Materials and Methods We have
overexpressed the TFPIV264M mutant and TFPIWT in human coronary artery
endothelial cells and compared the expression and activity levels
of the mutated protein relative to the TFPIWT. The protein levels
were determined by ELISA, the inhibitory activity of the proteins
was assessed with a chromogenic substrate assay. The mRNA level of
the two TFPI variants was determined using real time RT-PCR. MFOLD
was used to predict mRNA secondary structure.Results and Conclusions
TFPIV264M displayed increased protein levels and activity compared
to TFPIWT accompanied by an increase in mRNA levels of TFPIV264M
due to prolonged stability of TFPIV264M mRNA. The specific activity
of the TFPIV264M was similar to TFPIWT, indicating that the mutation
does not affect the enzymatic function of the protein.},
issn = {0049-3848},
keywords = {Endothelial cells, Expression, mRNA, Stability, Mutant, TFPI},
url = {http://www.sciencedirect.com/science/article/B6T1C-4TX6VXV-1/2/5cefc3ce88e719119d0e27a3a2efa12c}
}
@ARTICLE{Skrzypski2008,
author = {Skrzypski, Marcin},
title = {Quantitative reverse transcriptase real-time polymerase chain reaction
(qRT-PCR) in translational oncology: Lung cancer perspective},
journal = {Lung Cancer},
year = {2008},
volume = {59},
pages = {147--154},
number = {2},
month = feb,
abstract = {Summary Quantitative reverse transcriptase polymerase chain reaction
(qRT-PCR) is rapidly becoming a basic method in lung cancer research.
Analysis of transcriptional activity of tumor cells or detection
of tumor markers by this technique has the potential to change lung
cancer diagnosis and treatment. Quantitative RT-PCR is characterized
by unparalleled sensitivity and specificity, with very reliable reproducibility.
Its prime advantage for gene expression analysis is its broad dynamic
range of 107-fold. Moreover, it is cost-effective, feasible in every
day laboratory routine and efficient in terms of biological material
consumption. Still, there are a number of methodological aspects
that need to be carefully considered before it can sensibly be implemented
into clinical practice. Three major technical issues: the choice
of chemistries, gene expression data normalization and statistical
processing of the results will be specifically highlighted in this
review. Further, clinical applications of qRT-PCR will be thoroughly
discussed: detection and staging of lung cancer and construction
and validation of prognostic and predictive gene expression signatures.},
issn = {0169-5002},
keywords = {Quantitative reverse transcriptase real-time polymerase chain reaction
(qRT-PCR), Lung cancer, Normalization, Detection, Staging, Prognosis,
Predictive factors, Oligonucleotide microarrays},
url = {http://www.sciencedirect.com/science/article/B6T9C-4RH8S9W-2/2/f47314cc6099d9964f0fe4e5553db217}
}
@ARTICLE{Skurk2008,
author = {Skurk, Carsten and Wittchen, Frank and Suckau, Lennart and Witt,
Henning and Noutsias, Michael and Fechner, Henry and Schultheiss,
Heinz-Peter and Poller, Wolfgang},
title = {Description of a local cardiac adiponectin system and its deregulation
in dilated cardiomyopathy},
journal = {Eur. Heart J.},
year = {2008},
volume = {29},
pages = {1168--1180},
number = {9},
month = may,
abstract = {AimsDespite recent advances in medical therapy, heart failure remains
a leading cause for cardiovascular mortality, and its complex pathogenesis
is incompletely understood. This study was performed to identify
possible new therapeutic targets in dilated cardiomyopathy (DCM).
Methods and resultsOligonucleotide microarray analysis was performed
on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD
[≥] 55 mm, LVEF [≤] 55%, n = 5) and control subjects (LVEDD
< 55 mm, LVEF > 60%, no cardiac pathology, n = 4). Adiponectin, an
adipocytokine involved in cellular metabolism, survival, and immunmodulation,
was six-fold downregulated in DCM patients. Microarray data for adiponectin
were confirmed by TaqMan-PCR (9.2-fold downregulation, control n=
9 vs. DCM n= 9, respectively, P < 0.05). Immunohistological analysis
of EMBs showed significant downregulation of cardiac adiponectin
protein expression independent of serum adiponectin (P = 0.36, ns)
or serum TNF{alpha} concentrations (P = 0.46, ns). Neither the adiponectin
receptor 1 (adipo-R1) nor adipo-R2 was deregulated in early DCM.
Adiponectin mRNA and protein downregulation were confirmed in explanted
hearts of patients with advanced DCM (LVEF < 25%, n= 8). In vitro,
adiponectin incubation of neonatal rat ventricular myocytes led to
activation of the pro-survival kinase PKB/Akt, increased eNOS-phosphorylation,
and prevented stress-induced apoptosis of cardiomyocytes in an Akt-dependent
manner. Moreover, inhibition of adiponectin secretion was accompanied
by an increase in the expression of the cytokine and its receptors.
ConclusionThese data indicate the existence of a local cardiac adiponectin
system regulated independent of adiponectin and TNF{alpha} serum
levels and its disturbance in cardiac pathology. The study suggests
a role for adiponectin in the pathogenesis of DCM and implicates
the adipocytokine as a possible future therapeutic target in DCM.},
url = {http://eurheartj.oxfordjournals.org/cgi/content/abstract/29/9/1168}
}
@ARTICLE{Slabakova2011,
author = {Slabáková, Eva and Pernicová, Zuzana and Slaví?ková, Eva and Staršíchová,
Andrea and Kozubík, Alois and Sou?ek, Karel},
title = {TGF-?1-induced EMT of non-transformed prostate hyperplasia cells
is characterized by early induction of SNAI2/Slug},
journal = {The Prostate},
year = {2011},
volume = {71},
pages = {1332--1343},
number = {12},
abstract = {BACKGROUNDEpithelial–mesenchymal transition (EMT) underlying cancer
cell invasion and metastasis has been thoroughly studied in prostate
cancer. Although EMT markers have been clinically observed in benign
prostate hyperplasia, molecular events underlying the onset and progression
of EMT in benign prostate cells have not been described.METHODSEMT
in BPH-1 cells was induced by TGF-β1 treatment and the kinetics
of expression of EMT markers, regulators, and selected miRNAs was
assessed by western blotting and quantitative RT-PCR.RESULTSEMT in
BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug
and ZEB1 transcription factors, while changes in expression levels
of ZEB2 and miR-200 family members were observed after extended time
intervals. Invasive phenotype with EMT hallmarks, characterizing
tumorigenic clones derived from BPH-1 cells, was associated with
increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated
with significant changes in basal levels of miR-200 family members.
RNA interference revealed that SNAI2/Slug is crucial for TGF-β1-induced
vimentin up-regulation and migration of BPH-1 cells.CONCLUSIONSThis
study suggests that in BPH-1 cells the transcription factor SNAI2/Slug
is important for EMT initiation, while the ZEB family of transcription
factors in cooperation with the miR-200 family may oppose the reversal
of the EMT phenotype. Prostate 71:1332–1343, 2011. © 2011 Wiley-Liss,
Inc.},
doi = {10.1002/pros.21350},
issn = {1097-0045},
keywords = {epithelial–mesenchymal transition, miR-200 family, Slug, transforming
growth factor-β1, benign hyperplasia},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.21350}
}
@ARTICLE{Sladek2007,
author = {Sladek, Martin and Jindrakova, Zuzana and Bendova, Zdenka and Sumova,
Alena},
title = {Postnatal ontogenesis of the circadian clock within the rat liver},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {292},
pages = {R1224--1229},
number = {3},
month = mar,
abstract = {In mammals, the circadian oscillator within the suprachiasmatic nuclei
(SCN) entrains circadian clocks in numerous peripheral tissues. Central
and peripheral clocks share a molecular core clock mechanism governing
daily time measurement. In the rat SCN, the molecular clockwork develops
gradually during postnatal ontogenesis. The aim of the present work
was to elucidate when during ontogenesis the expression of clock
genes in the rat liver starts to be rhythmic. Daily profiles of mRNA
expression of clock genes Per1, Per2, Cry1, Clock, Rev-Erb{alpha},
and Bmal1 were analyzed in the liver of fetuses at embryonic day
20 (E20) or pups at postnatal age 2 (P2), P10, P20, P30, and in adults
by real-time RT-PCR. At E20, only a high-amplitude rhythm in Rev-Erb{alpha}
and a low-amplitude variation in Cry1 but no clear circadian rhythms
in expression of other clock genes were detectable. At P2, a high-amplitude
rhythm in Rev-Erb{alpha} and a low-amplitude variation in Bmal1 but
no rhythms in expression of other genes were detected. At P10, significant
rhythms only in Per1 and Rev-Erb{alpha} expression were present.
At P20, clear circadian rhythms in the expression of Per1, Per2,
Rev-Erb{alpha}, and Bmal1, but not yet of Cry1 and Clock, were detected.
At P30, all clock genes were expressed rhythmically. The phase of
the rhythms shifted between all studied developmental periods until
the adult stage was achieved. The data indicate that the development
of the molecular clockwork in the rat liver proceeds gradually and
is roughly completed by 30 days after birth.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/292/3/R1224}
}
@ARTICLE{Slater2010,
author = {Slater, F.R. and Johnson, C.R. and Blackall, L.L. and Beiko, R.G.
and Bond, P.L.},
title = {Monitoring associations between clade-level variation, overall community
structure and ecosystem function in enhanced biological phosphorus
removal (EBPR) systems using terminal-restriction fragment length
polymorphism (T-RFLP)},
journal = {Water Research},
year = {2010},
volume = {44},
pages = {4908--4923},
number = {17},
month = sep,
abstract = {The role of Candidatus "Accumulibacter phosphatis" (Accumulibacter)
in enhanced biological phosphorus removal (EBPR) is well established
but the relevance of different Accumulibacter clades to the performance
of EBPR systems is unknown. We developed a terminal-restriction fragment
length polymorphism (T-RFLP) technique to monitor changes in the
relative abundance of key members of the bacterial community, including
Accumulibacter clades, in four replicate mini-sequencing batch reactors
(mSBRs) operated for EBPR over a 35-day period. The ability of the
T-RFLP technique to detect trends was confirmed using fluorescence
in situ hybridisation (FISH). EBPR performance varied between reactors
and over time; by day 35, performance was maintained in mSBR2 whilst
it had deteriorated in mSBR1. However, reproducible trends in structure-function
relationships were detected in the mSBRs. EBPR performance was strongly
associated with the relative abundance of total Accumulibacter. A
shift in the ratio of the dominant Accumulibacter clades was also
detected, with Type IA associated with good EBPR performance and
Type IIC associated with poor EBPR performance. Changes in ecosystem
function of the mSBRs in the early stages of the experiment were
more closely associated with changes in the abundance of (unknown)
members of the flanking community than of either Accumulibacter or
Candidatus "Competibacter phosphatis". This study therefore reveals
a hitherto unrecorded and complex relationship between Accumulibacter
clades, the flanking community and ecosystem function of laboratory-scale
EBPR systems.},
booktitle = {Microbial ecology of drinking water and waste water treatment processes},
issn = {0043-1354},
keywords = {Ecological selection, Candidatus "Accumulibacter phosphatis" clades,
Candidatus "Competibacter phosphatis", Terminal-restriction fragment
length polymorphism},
url = {http://www.sciencedirect.com/science/article/B6V73-50J9GST-B/2/df07632ed4eb03837b1cdd7d1154d5b7}
}
@ARTICLE{Slebos2006,
author = {Slebos, Robbert J.C. and Yi, Yajun and Ely, Kim and Carter, Jesse
and Evjen, Amy and Zhang, Xueqiong and Shyr, Yu and Murphy, Barbara
M. and Cmelak, Anthony J. and Burkey, Brian B. and Netterville, James
L. and Levy, Shawn and Yarbrough, Wendell G. and Chung, Christine
H.},
title = {Gene Expression Differences Associated with Human Papillomavirus
Status in Head and Neck Squamous Cell Carcinoma},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {701--709},
number = {3},
month = feb,
abstract = {Human papillomavirus (HPV) is associated with a subset of head and
neck squamous cell carcinoma (HNSCC). Between 15% and 35% of HNSCCs
harbor HPV DNA. Demographic and exposure differences between HPV-positive
(HPV+) and negative (HPV-) HNSCCs suggest that HPV+ tumors may constitute
a subclass with different biology, whereas clinical differences have
also been observed. Gene expression profiles of HPV+ and HPV- tumors
were compared with further exploration of the biological effect of
HPV in HNSCC. Thirty-six HNSCC tumors were analyzed using Affymetrix
Human 133U Plus 2.0 GeneChip and for HPV by PCR and real-time PCR.
Eight of 36 (22%) tumors were positive for HPV subtype 16. Statistical
analysis using Significance Analysis of Microarrays based on HPV
status as a supervising variable resulted in a list of 91 genes that
were differentially expressed with statistical significance. Results
for a subset of these genes were verified by real-time PCR. Genes
highly expressed in HPV+ samples included cell cycle regulators (p16INK4A,
p18, and CDC7) and transcription factors (TAF7L, RFC4, RPA2, and
TFDP2). The microarray data were also investigated by mapping genes
by chromosomal location (DIGMAP). A large number of genes on chromosome
3q24-qter had high levels of expression in HPV+ tumors. Further investigation
of differentially expressed genes may reveal the unique pathways
in HPV+ tumors that may explain the different natural history and
biological properties of these tumors. These properties may be exploited
as a target of novel therapeutic agents in HNSCC treatment.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/3/701}
}
@ARTICLE{Slegtenhorst2007,
author = {van Slegtenhorst, Marjon and Khabibullin, Damir and Hartman, Tiffiney
R. and Nicolas, Emmanuelle and Kruger, Warren D. and Henske, Elizabeth
Petri},
title = {The Birt-Hogg-Dube and Tuberous Sclerosis Complex Homologs Have Opposing
Roles in Amino Acid Homeostasis in Schizosaccharomyces pombe},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {24583--24590},
number = {34},
month = aug,
abstract = {Birt-Hogg-Dube (BHD) is a tumor suppressor gene disorder characterized
by skin hamartomas, cystic lung disease, and renal cell carcinoma.
The fact that hamartomas, lung cysts, and renal cell carcinoma can
also occur in tuberous sclerosis complex (TSC) suggests that the
BHD and TSC proteins may function within a common pathway. To evaluate
this hypothesis, we deleted the BHD homolog in Schizosaccharomyces
pombe. Expression profiling revealed that six permease and transporter
genes, known to be down-regulated in {Delta}tsc1 and {Delta}tsc2,
were up-regulated in {Delta}bhd, and levels of specific intracellular
amino acids known to be low in {Delta}tsc1 and {Delta}tsc2 were elevated
in {Delta}bhd. This "opposite" profile was unexpected, given the
overlapping clinical phenotypes. The TSC1/2 proteins inhibit Rheb
in mammals, and Tsc1/Tsc2 inhibit Rhb1 in S. pombe. Expression of
a hypomorphic allele of rhb1+ dramatically increased permease expression
levels in {Delta}bhd but not in wild-type yeast. Loss of Bhd sensitized
yeast to rapamycin-induced increases in permease expression levels,
and rapamycin induced lethality in {Delta}bhd yeast expressing the
hypomorphic Rhb1 allele. In S. pombe, it is known that Rhb1 binds
Tor2, and Tor2 inhibition leads to up-regulation of permeases including
those that are regulated by Bhd. Our data, therefore, suggest that
Bhd activates Tor2. If the mammalian BHD protein, folliculin, similarly
activates mammalian target of rapamycin, it will be of great interest
to determine how mammalian target of rapamycin inhibition in BHD
patients and mammalian target of rapamycin activation in TSC patients
lead to overlapping clinical phenotypes.},
url = {http://www.jbc.org/cgi/content/abstract/282/34/24583}
}
@ARTICLE{Sleiman2011,
author = {Sleiman, Sama F. and Langley, Brett C. and Basso, Manuela and Berlin,
Jill and Xia, Li and Payappilly, Jimmy B. and Kharel, Madan K. and
Guo, Hengchang and Marsh, J. Lawrence and Thompson, Leslie Michels
and Mahishi, Lata and Ahuja, Preeti and MacLellan, W. Robb and Geschwind,
Daniel H. and Coppola, Giovanni and Rohr, Jurgen and Ratan, Rajiv
R.},
title = {Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological
Intersection between Cancer and Neurodegeneration},
journal = {J. Neurosci.},
year = {2011},
volume = {31},
pages = {6858--6870},
number = {18},
month = may,
abstract = {Oncogenic transformation of postmitotic neurons triggers cell death,
but the identity of genes critical for degeneration remain unclear.
The antitumor antibiotic mithramycin prolongs survival of mouse models
of Huntington's disease in vivo and inhibits oxidative stress-induced
death in cortical neurons in vitro. We had correlated protection
by mithramycin with its ability to bind to GC-rich DNA and globally
displace Sp1 family transcription factors. To understand how antitumor
drugs prevent neurodegeneration, here we use structure-activity relationships
of mithramycin analogs to discover that selective DNA-binding inhibition
of the drug is necessary for its neuroprotective effect. We identify
several genes (Myc, c-Src, Hif1, and p21waf1/cip1) involved in neoplastic
transformation, whose altered expression correlates with protective
doses of mithramycin or its analogs. Most interestingly, inhibition
of one these genes, Myc, is neuroprotective, whereas forced expression
of Myc induces Rattus norvegicus neuronal cell death. These results
support a model in which cancer cell transformation shares key genetic
components with neurodegeneration.},
comment = {10.1523/JNEUROSCI.0710-11.2011},
url = {http://www.jneurosci.org/cgi/content/abstract/31/18/6858}
}
@ARTICLE{Slepak2007,
author = {Slepak, Tatiana I. and Tang, Manshu and Slepak, Vladlen Z. and Lai,
Kent},
title = {Involvement of endoplasmic reticulum stress in a novel Classic Galactosemia
model},
journal = {Molecular Genetics and Metabolism},
year = {2007},
volume = {92},
pages = {78--87},
number = {1-2},
month = sep,
abstract = {Inherited deficiency of galactose-1-phosphate uridyltransferase (GALT)
activity in humans leads to a potentially lethal disorder called
Classic Galactosemia. It is well known that patients often accumulate
high levels of galactose metabolites such as galactose-1-phosphate
(gal-1-p) in their tissues. However, specific targets of gal-1-p
and other accumulated metabolites remain uncertain. In this study,
we developed a new model system to study this toxicity using primary
fibroblasts derived from galactosemic patients. GALT activity was
reconstituted in these primary cells through lentivirus-mediated
gene transfer. Gene expression profiling showed that GALT-deficient
cells, but not normal cells, responded to galactose challenge by
activating a set of genes characteristic of endoplasmic reticulum
(ER) stress. Western blot analysis showed that the master regulator
of ER stress, BiP, was up-regulated at least threefold in these cells
upon galactose challenge. We also found that treatment of these cells
with galactose, but not glucose or hexose-free media reduced Ca2+
mobilization in response to activation of Gq-coupled receptors. To
explore whether the muted Ca2+ mobilization is related to reduced
inositol turnover, we discovered that gal-1-p competitively inhibited
human inositol monophosphatase (hIMPase1). We hypothesize that galactose
intoxication under GALT-deficiency resulted from accumulation of
toxic galactose metabolite products, which led to the accumulation
of unfolded proteins, altered calcium homeostasis, and subsequently
ER stress.},
issn = {1096-7192},
keywords = {Galactosemia, Galactose-1-phosphate, Inositol monophosphatase, Endoplasmic
reticulum stress, Unfolded protein response, GRP78},
url = {http://www.sciencedirect.com/science/article/B6WNG-4P7FD3G-2/2/1a46fb2b0cc608898a8b2a8da69552d8}
}
@ARTICLE{Slevin2009,
author = {Slevin, Mark and Krupinski, Jerzy and Rovira, Norma and Turu, Marta
and Luque, Ana and Baldellou, Maribel and Sanfeliu, Coral and de
Vera, Nuria and Badimon, Lina},
title = {Identification of pro-angiogenic markers in blood vessels from stroked-affected
brain tissue using laser-capture microdissection},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {113},
number = {1},
abstract = {BACKGROUND:Angiogenesis correlates with patient survival following
acute ischaemic stroke, and survival of neurons is greatest in tissue
undergoing angiogenesis. Angiogenesis is critical for the development
of new microvessels and leads to re-formation of collateral circulation,
reperfusion, enhanced neuronal survival and improved recovery.RESULTS:Here,
we have isolated active (CD105/Flt-1 positive) and inactive (CD105/Flt-1
minus (n=5) micro-vessel rich-regions from stroke-affected and contralateral
tissue of patients using laser-capture micro-dissection. Areas were
compared for pro- and anti-angiogenic gene expression using targeted
TaqMan microfluidity cards containing 46 genes and real-time PCR.
Further analysis of key gene de-regulation was performed by immunohistochemistry
to define localization and expression patterns of identified markers
and de novo synthesis by human brain microvessel endothelial cells
(HBMEC) was examined following oxygen-glucose deprivation (OGD).
Our data revealed that seven pro-angiogenic genes were notably up-regulated
in CD105 positive microvessel rich regions. These were, beta-catenin,
neural cell adhesion molecule (NRCAM), matrix metalloproteinase-2
(MMP-2), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1),
hepatocyte growth factor-alpha (HGF-alpha), monocyte chemottractant
protein-1 (MCP-1) and and Tie-2 as well as c-kit. Immunohistochemistry
demonstrated strong staining of MMP-2, HGF-alpha, MCP-1 and Tie-2
in stroke-associated regions of active remodeling in association
with CD105 positive staining. In vitro, OGD stimulated production
of Tie-2, MCP-1 and MMP-2 in HBMEC, demonstrated a de novo response
to hypoxia.CONCLUSION:In this work we have identified concurrent
activation of key angiogenic molecules associated with endothelial
cell migration, differentiation and tube-formation, vessel stabilization
and stem cell homing mechanisms in areas of revascularization. Therapeutic
stimulation of these processes in all areas of damaged tissue might
improve morbidity and mortality from stroke.},
doi = {10.1186/1471-2164-10-113},
issn = {1471-2164},
pubmedid = {19292924},
url = {http://www.biomedcentral.com/1471-2164/10/113}
}
@ARTICLE{Sloan2011,
author = {Sloan, Daniel B. And Keller, Stephen R. And Berardi, Andrea E. And
Sanderson, Brian J. And Karpovich, John F. And Taylor, Douglas R.},
title = {De novo transcriptome assembly and polymorphism detection in the
flowering plant Silene vulgaris (Caryophyllaceae)},
journal = {Molecular Ecology Resources},
year = {2011},
pages = {no--no},
abstract = {Members of the angiosperm genus Silene are widely used in studies
of ecology and evolution, but available genomic and population genetic
resources within Silene remain limited. Deep transcriptome (i.e.
expressed sequence tag or EST) sequencing has proven to be a rapid
and cost-effective means to characterize gene content and identify
polymorphic markers in non-model organisms. In this study, we report
the results of 454 GS-FLX Titanium sequencing of a polyA-selected
and normalized cDNA library from Silene vulgaris. The library was
generated from a single pool of transcripts, combining RNA from leaf,
root and floral tissue from three genetically divergent European
subpopulations of S. vulgaris. A single full-plate 454 run produced
959Â 520 reads totalling 363.6Â Mb of sequence data with an average
read length of 379.0Â bp after quality trimming and removal of custom
library adaptors. We assembled 832Â 251 (86.7%) of these reads into
40Â 964 contigs, which have a total length of 25.4Â Mb and can be
organized into 18 178 graph-based clusters or ‘isogroups’. Assembled
sequences were annotated based on homology to genes in multiple public
databases. Analysis of sequence variants identified 13Â 432 putative
single-nucleotide polymorphisms (SNPs) and 1320 simple sequence repeats
(SSRs) that are candidates for microsatellite analysis. Estimates
of nucleotide diversity from 1577 contigs were used to generate genome-wide
distributions that revealed several outliers with high diversity.
All of these resources are publicly available through NCBI and/or
our website (http://silenegenomics.biology.virginia.edu) and should
provide valuable genomic and population genetic tools for the Silene
research community.},
doi = {10.1111/j.1755-0998.2011.03079.x},
issn = {1755-0998},
keywords = {454 sequencing, microsatellites, nucleotide diversity, Silene vulgaris,
single-nucleotide polymorphisms, transcriptome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-0998.2011.03079.x}
}
@ARTICLE{Slofstra2007,
author = {Slofstra, Sjoukje H. and Groot, Angelique P. and Obdeijn, Maartje
H. P. and Reitsma, Pieter H. and ten Cate, Hugo and Spek, C. Arnold},
title = {Gene Expression Profiling Identifies C/EBP{delta} as a Candidate
Regulator of Endotoxin-induced Disseminated Intravascular Coagulation},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2007},
volume = {176},
pages = {602--609},
number = {6},
month = sep,
abstract = {Rationale: A runaway inflammatory response to systemic infection or
severe trauma is characterized by the activation of a diversity of
pathways, ultimately resulting in the development of disseminated
intravascular coagulation (DIC) and multiorgan failure. Objectives:
Despite increased fundamental knowledge of the pathogenesis of DIC,
the exact molecular mechanisms remain elusive. We aimed therefore
to improve our understanding of the molecular pathways underlying
endotoxin-induced DIC. Methods: We performed large-scale gene expression
profiling in the liver of mice during the onset of endotoxin-induced
DIC. The relevance of an identified candidate gene involved in endotoxin-induced
DIC was subsequently assessed in the generalized Shwartzman reaction.
Measurements and Main Results: Approximately 5% of over 20,000 genes
were differentially regulated. In addition to well-established sepsis-associated
genes, such as macrophage inflammatory protein 1, plasminogen activator
inhibitor 1, CD14, and A20, we identified several novel candidates
for inflammatory disease of which the transcription factor C/EBP{delta}
(CAAT/enhancer binding protein {delta}) was studied further. Induction
of DIC in C/EBP{delta}-deficient mice decreased endotoxin-induced
systemic inflammation as compared with wild-type mice, as evident
from decreased plasma levels of tumor necrosis factor-{alpha} and
IL-6. In addition, C/EBP{delta} deficiency partly protected against
DIC-induced mortality. Interestingly, C/EBP{delta} deficiency seemed
mainly protective by improving renal function. This latter notion
was confirmed in an experimental model of renal ischemia/reperfusion
injury in which C/EBP{delta} deficiency reduced ischemia/reperfusion-induced
creatinine and urea levels. Conclusions: Our results endorse the
usefulness of gene expression profiling in identifying novel mediators
of DIC by showing that C/EBP{delta} regulates specific pathologic
features of this endotoxin-induced syndrome.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/176/6/602}
}
@ARTICLE{Slonim2009,
author = {Slonim, Donna K. and Koide, Keiko and Johnson, Kirby L. and Tantravahi,
Umadevi and Cowan, Janet M. and Jarrah, Zina and Bianchi, Diana W.},
title = {Functional genomic analysis of amniotic fluid cell-free mRNA suggests
that oxidative stress is significant in Down syndrome fetuses},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {9425--9429},
number = {23},
month = jun,
abstract = {To characterize the differences between second trimester Down syndrome
(DS) and euploid fetuses, we used Affymetrix microarrays to compare
gene expression in uncultured amniotic fluid supernatant samples.
Functional pathway analysis highlighted the importance of oxidative
stress, ion transport, and G protein signaling in the DS fetuses.
Further evidence supporting these results was derived by correlating
the observed gene expression patterns to those of small molecule
drugs via the Connectivity Map. Our results suggest that there are
secondary adverse consequences of DS evident in the second trimester,
leading to testable hypotheses about possible antenatal therapy for
DS.},
url = {http://www.pnas.org/cgi/content/abstract/106/23/9425}
}
@ARTICLE{Slonimsky2010,
author = {Slonimsky, Alexandra and Levy, Itzchak and Kohn, Yoav and Rigbi,
Amihai and Ben-Asher, Edna and Lancet, Doron and Agam, Galila and
Lerer, Bernard},
title = {Lymphoblast and brain expression of AHI1 and the novel primate-specific
gene, C6orf217, in schizophrenia and bipolar disorder},
journal = {Schizophrenia Research},
year = {2010},
volume = {120},
pages = {159--166},
number = {1-3},
month = jul,
abstract = {Association with schizophrenia of the Abelson Helper Integration Site
1 (AHI1) gene on chromosome 6q23 and the adjacent primate-specific
gene, C6orf217, was demonstrated in an inbred, Arab Israeli family
sample and replicated in an Icelandic case control sample. Further
support was provided by a second replication in a large European
sample and a meta-analysis that supported association with schizophrenia
of all seven alleles overtransmitted to affected subjects in the
original study. We examined constitutive expression of AHI1 and C6orf217
in immortalized lymphoblasts of patients from the Arab Israeli family
sample in which the association with schizophrenia was originally
discovered and population-matched normal controls, and in post-mortem
brain of patients with schizophrenia and bipolar (BP) disorder and
control subjects from the Stanley Medical Research Institute Collection.
We found a significant effect of diagnostic group in the lymphoblast
sample (F = 5.72; df = 2,39; p = 0.006). Patients with early age
of onset had higher AHI1 expression than controls and later onset
patients (p = 0.002; 0.03 respectively). C6orf217 expression in lymphoblasts
was too low to measure. We found no difference in brain expression
of AHI1 in schizophrenia or BP patients compared to controls. However,
there was a genotypic difference in AHI1 expression for SNP rs9321501,
which was strongly associated with schizophrenia in the original
study. Genotypes that included the undertransmitted C allele (CC/AC)
showed lower expression than the homozygous AA genotype (F = 4.73,
df = 2,83; p = 0.028). There was no significant difference in brain
expression of C6orf217 between patients and controls and no genotypic
effect. This study provides further evidence for involvement of AHI1
in susceptibility to schizophrenia.},
issn = {0920-9964},
keywords = {Schizophrenia, AHI1, C6orf217, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6TC2-50237G7-1/2/91bda9f630eb635f7eba0114f29b0632}
}
@ARTICLE{Slotkin2007,
author = {Slotkin, Theodore A. and Seidler, Frederic J.},
title = {Comparative developmental neurotoxicity of organophosphates in vivo:
Transcriptional responses of pathways for brain cell development,
cell signaling, cytotoxicity and neurotransmitter systems},
journal = {Brain Research Bulletin},
year = {2007},
volume = {72},
pages = {232--274},
number = {4-6},
month = may,
abstract = {Organophosphates affect mammalian brain development through a variety
of mechanisms beyond their shared property of cholinesterase inhibition.
We used microarrays to characterize similarities and differences
in transcriptional responses to chlorpyrifos and diazinon, assessing
defined gene groupings for the pathways known to be associated with
the mechanisms and/or outcomes of chlorpyrifos-induced developmental
neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos
(1 mg/kg) or diazinon (1 or 2 mg/kg) on postnatal days 1-4 and evaluated
gene expression profiles in brainstem and forebrain on day 5; these
doses produce little or no cholinesterase inhibition. We evaluated
pathways for general neural cell development, cell signaling, cytotoxicity
and neurotransmitter systems, and identified significant differences
for >60% of 252 genes. Chlorpyrifos elicited major transcriptional
changes in genes involved in neural cell growth, development of glia
and myelin, transcriptional factors involved in neural cell differentiation,
cAMP-related cell signaling, apoptosis, oxidative stress, excitotoxicity,
and development of neurotransmitter synthesis, storage and receptors
for acetylcholine, serotonin, norepinephrine and dopamine. Diazinon
had similar effects on many of the same processes but also showed
major differences from chlorpyrifos. Our results buttress the idea
that different organophosphates target multiple pathways involved
in neural cell development but also that they deviate in key aspects
that may contribute to disparate neurodevelopmental outcomes. Equally
important, these pathways are compromised at exposures that are unrelated
to biologically significant cholinesterase inhibition and its associated
signs of systemic toxicity. The approach used here demonstrates how
planned comparisons with microarrays can be used to screen for developmental
neurotoxicity.},
issn = {0361-9230},
keywords = {Brain development, Chlorpyrifos, Diazinon, Microarrays, Neurotoxicity,
Organophosphate insecticides},
url = {http://www.sciencedirect.com/science/article/B6SYT-4MWY17Y-1/2/e6f444c1f4b5c75e1a2993e849747ca6}
}
@ARTICLE{Slotkin2008,
author = {Slotkin, Theodore A. and Seidler, Frederic J. and Fumagalli, Fabio},
title = {Targeting of neurotrophic factors, their receptors, and signaling
pathways in the developmental neurotoxicity of organophosphates in
vivo and in vitro},
journal = {Brain Research Bulletin},
year = {2008},
volume = {76},
pages = {424--438},
number = {4},
month = jul,
abstract = {Neurotrophic factors control neural cell differentiation and assembly
of neural circuits. We previously showed that organophosphate pesticides
differentially regulate members of the fibroblast growth factor (fgf)
gene family. We administered chlorpyrifos and diazinon to neonatal
rats on postnatal days 1-4 at doses devoid of systemic toxicity or
growth impairment, and spanning the threshold for barely-detectable
cholinesterase inhibition. We evaluated the impact on gene families
for different classes of neurotrophic factors. Using microarrays,
we examined the regional expression of mRNAs encoding the neurotrophins
(ntfs), brain-derived neurotrophic factor (bdnf), nerve growth factor
(ngf), the wnt and fzd gene families and the corresponding receptors.
Chlorpyrifos and diazinon both had widespread effects on the fgf,
ntf, wnt and fzd families but much less on the bdnf and ngf groups.
However, the two organophosphates showed disparate effects on a number
of key neurotrophic factors. To determine if the actions were mediated
directly on differentiating neurons, we tested chlorpyrifos in PC12
cells, an in vitro model of neural cell development. Effects in PC12
cells mirrored many of those for members of the fgf, ntf and wnt
families, as well as the receptors for the ntfs, especially during
early differentiation, the stage known to be most susceptible to
disruption by organophosphates. Our results suggest that actions
on neurotrophic factors provide a mechanism for the developmental
neurotoxicity of low doses of organophosphates, and, since effects
on expression of the affected genes differed with test agent, may
help explain regional disparities in effects and critical periods
of vulnerability.},
issn = {0361-9230},
keywords = {Brain-derived neurotrophic factor, Brain development, Chlorpyrifos,
Diazinon, Fibroblast growth factor, fzd gene family, Microarrays,
Nerve growth factor, Neurotoxicity, Neurotrophic factors, Organophosphate
insecticides, PC12 cells, Tyrosine kinase, wnt gene family},
url = {http://www.sciencedirect.com/science/article/B6SYT-4RR7WHN-1/2/b031a37a3ae48764ab81a10bdc540009}
}
@ARTICLE{Sluimer2007,
author = {Sluimer, Judith C. and Kisters, Natasja and Cleutjens, Kitty B. and
Volger, Oscar L. and Horrevoets, Anton J. and van den Akker, Luc
H. and Bijnens, Ann-Pascale J. and Daemen, Mat J.},
title = {Dead or alive: gene expression profiles of advanced atherosclerotic
plaques from autopsy and surgery},
journal = {Physiol Genomics},
year = {2007},
volume = {30},
pages = {335--341},
number = {3},
month = aug,
abstract = {Since inclusion of atherosclerotic tissues from different sources
is often indispensable to study the full atherogenic spectrum, we
investigated to what extent the expression profiles of advanced,
stable atherosclerotic lesions obtained during autopsy and surgery
are comparable. The gene expression profiles of human carotids with
advanced atherosclerosis obtained at autopsy and at vascular surgery
were studied by microarray analysis. Expression analysis was performed
both at the single gene (Rosetta, Gene Ontology) and at the pathway
level using Ingenuity and Gene Set Enrichment Analysis. In addition,
mRNA and protein expression levels were validated using quantitative
(q) RT-PCR and immunohistochemistry on unrelated advanced carotid
lesions from autopsy and surgery. Microarray analysis indicated that
the 97.2% of genes showed similar expression levels in advanced atherosclerotic
lesions from autopsy and surgery. While the expression data revealed
no differences in common atherosclerotic related pathways such as
lipid metabolism and inflammation, the differentially expressed genes
were mainly involved in basal cell metabolism and hypoxia driven
pathways. qRT-PCR confirmed the differential expression of hypoxia-driven
genes VEGF-A (2.3-fold {uparrow}), glucose transporter (GLUT)-1 (2.5-fold
{uparrow}), GLUT3 (8.3-fold {uparrow}), and hexokinase 1 (2.4-fold
{uparrow}) in autopsy vs. surgical specimens. Immunohistochemistry
revealed that the transcriptional differences in these hypoxia-related
genes were not reflected at the protein level. The gene expression
profiles of advanced atherosclerotic lesions from autopsy and surgery
are largely similar. However, >500 genes, mostly involved in basal
cell metabolism and hypoxia were differentially expressed at mRNA,
but not at the protein level.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/30/3/335}
}
@ARTICLE{Slyvka2011,
author = {Slyvka, Yuriy and Wang, Zhenchao and Yee, Jennifer and Inman, Sharon
R. and Nowak, Felicia V.},
title = {Antioxidant diet, gender and age affect renal expression of nitric
oxide synthases in obese diabetic rats},
journal = {Nitric Oxide},
year = {2011},
volume = {24},
pages = {50--60},
number = {1},
month = jan,
abstract = {Development of diabetic nephropathy (DN) is associated with decreased
renal nitric oxide production and increased oxidative stress. We
studied nitric oxide synthase (NOS) expression in kidney of obese
Zucker fa/fa rats, a model of Type 2 obesity-related DN. Male and
female rats received a regular (REG) or antioxidant-fortified (AO)
diet starting at age 4 weeks. Quantitative PCR and immunoblot analyses
were performed on kidney cortex and medulla to determine levels of
endothelial, neuronal and inducible NOS at 6, 13 and 20 weeks of
age. Multiple antibody-specific proteins were detected for each form.
These may represent monomeric splice forms, post-translationally
modified forms and their dimers, consistent with the known complexity
of regulation of these enzymes. Levels of eNOS and nNOS are higher
in males than females at 6 weeks on the REG diet and 13 weeks on
either diet; the relationship is reversed in females at 6 weeks on
the AO diet. Levels of eNOS and nNOS are lower on the AO diet compared
to REG, in males at 6 and 13 weeks and females at 13 weeks; the reverse
is seen in 6 week females and 20 week males. All three isoforms show
peak levels in the younger animals, at 6 or 13 weeks. Better preservation
of kidney function is associated with higher prevalence of dimers
with potential to increase production of NO and lower levels of potentially
harmful monomers. Differential expression of NOS isoforms may be
linked to renal functional and histopathological changes in this
rat model of DN.},
issn = {1089-8603},
keywords = {Type 2 diabetes, Nephropathy, Antioxidants, Nitric oxide synthase,
Alternative splicing, Obese Zucker rats},
url = {http://www.sciencedirect.com/science/article/pii/S108986031000443X}
}
@ARTICLE{Sladek2007a,
author = {Sládek, Martin and Rybová, Markéta and Jindráková, Zuzana and Zemanová,
Zdena and Polidarová, Lenka and Mrnka, Libor and O'Neill, John and
Pácha, Jirí and Sumová, Alena},
title = {Insight Into the Circadian Clock Within Rat Colonic Epithelial Cells},
journal = {Gastroenterology},
year = {2007},
volume = {133},
pages = {1240--1249},
number = {4},
month = oct,
abstract = {Background & Aims: The gastrointestinal tract exhibits diurnal rhythms
in many physiologic functions. These rhythms are driven by food intake
but are also preserved during food deprivation, suggesting the presence
of endogenous circadian rhythmicity. The aim of the study was to
provide insight into the circadian core clock mechanism within the
rat colon. Moreover, the potency of a restricted feeding regime to
shift the circadian clock in the colon was tested. The question of
whether the colonic clock drives circadian expression in NHE3, an
electroneutral Na+/H+ exchanger, was also addressed. Methods: Daily
profiles in expression of clock genes Per1, Per2, Cry1, Bmal1, Clock,
and Rev-erb[alpha], and the NHE3 transporter were examined by reverse
transcriptase-polymerase chain reaction and their mRNA levels, as
well as PER1 and BMAL1 protein levels, were localized in the colonic
epithelium by in situ hybridization and immunocytochemistry, respectively.
Results: Expression of Per1, Per2, Cry1, Bmal1, Clock, Rev-erb[alpha],
and NHE3, as well as PER1 and BMAL1 protein levels, exhibited circadian
rhythmicity in the colon. The rhythms were in phase with those in
the liver but phase-delayed relative to the master clock in the suprachiasmatic
nucleus. Restricted feeding entrained the clock in the colon, because
rhythms in clock genes as well as in NHE3 expression were phase-advanced
similarly to the clock in the liver. Conclusions: The rat colon harbors
a circadian clock. The colonic clock is likely to drive rhythmic
NHE3 expression. Restricted feeding resets the colonic clock similarly
to the clock in the liver.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4NWCD8R-2/2/a539271ea68406100683d7ff3ed8d681}
}
@ARTICLE{Small2005,
author = {Small, Christopher L. and Shima, James E. and Uzumcu, Mehmet and
Skinner, Michael K. and Griswold, Michael D.},
title = {Profiling Gene Expression During the Differentiation and Development
of the Murine Embryonic Gonad},
journal = {Biol Reprod},
year = {2005},
volume = {72},
pages = {492--501},
number = {2},
month = feb,
abstract = {The application of microarray technology to the study of mammalian
organogenesis can provide greater insights into the steps necessary
to elicit a functionally competent tissue. To this end, a temporal
profile of gene expression was generated with the purpose of identifying
changes in gene expression occurring within the developing male and
female embryonic gonad. Gonad tissue was collected from mouse embryos
at 11.5, 12.5, 14.5, 16.5, and 18.5 days postcoitum (dpc) and relative
steady-state levels of mRNA were determined using the Affymetrix
MGU74v2 microarray platform. Statistical analysis produced 3693 transcripts
exhibiting differential expression during male and/or female gonad
development. At 11.5 dpc, the gonad is morphologically indifferent,
but at 12.5 dpc, transitions to a male or female phenotype are discernible
by the appearance of testicular cords. A number of genes are expressed
during this period and many share similar expression profiles in
both sexes. As expected, the expression of two well-known sex determination
genes, specifically Sry and Sox9, is unique to the testis. Beyond
12.5 dpc, differential gene expression becomes increasingly evident
as the male and female tissue morphologically and physiologically
diverges. This is evident by two unique waves of transcriptional
activity occurring after 14.5 dpc in the male and female. With this
study, a large number of transcripts comprising the murine transcriptome
can be examined throughout male and female embryonic gonad development
and allow for a more complete description of gonad differentiation
and development.},
url = {http://www.biolreprod.org/cgi/content/abstract/72/2/492}
}
@ARTICLE{Smalley2007,
author = {Smalley, Matthew and Iravani, Marjan and Leao, Maria and Grigoriadis,
Anita and Kendrick, Howard and Dexter, Tim and Fenwick, Kerry and
Regan, Joseph and Britt, Kara and McDonald, Sarah and Lord, Christopher
and MacKay, Alan and Ashworth, Alan},
title = {Regulator of G-protein signalling 2 mRNA is differentially expressed
in mammary epithelial subpopulations and over-expressed in the majority
of breast cancers},
journal = {Breast Cancer Research},
year = {2007},
volume = {9},
pages = {R85},
number = {6},
abstract = {INTRODUCTION:To understand which signalling pathways become deregulated
in breast cancer, it is necessary to identify functionally significant
gene expression patterns in the stem, progenitor, transit amplifying
and differentiated cells of the mammary epithelium. We have previously
used the markers 33A10, CD24 and Sca-1 to identify mouse mammary
epithelial cell subpopulations. We now investigate the relationship
between cells expressing these markers and use gene expression microarray
analysis to identify genes differentially expressed in the cell populations.METHODS:Freshly
isolated primary mouse mammary epithelial cells were separated on
the basis of staining with the 33A10 antibody and an a-Sca-1 antibody.
The populations identified were profiled using gene expression microarray
analysis. Gene expression patterns were confirmed on normal mouse
and human mammary epithelial subpopulations and were examined in
a panel of breast cancer samples and cell lines.RESULTS:Analysis
of the separated populations demonstrated that Sca-1- 33A10High stained
cells were estrogen receptor a (Esr1)- luminal epithelial cells,
whereas Sca-1+ 33A10Low/- stained cells were a mix of nonepithelial
cells and Esr1+ epithelial cells. Analysis of the gene expression
data identified the gene Rgs2 (regulator of G-protein signalling
2) as being highly expressed in the Sca-1- 33A10Low/- population,
which included myoepithelial/basal cells. RGS2 has previously been
described as a regulator of angiotensin II receptor signalling. Gene
expression analysis by quantitative real-time RT-PCR of cells separated
on the basis of CD24 and Sca-1 expression confirmed that Rgs2 was
more highly expressed in mouse myoepithelial/basal mammary cells
than luminal cells. This expression pattern was conserved in normal
human breast cells. Functional analysis demonstrated RGS2 to be a
modulator of oxytocin receptor signalling. The potential significance
of RGS2 expression in breast cancer was demonstrated by semi-quantitative
RT-PCR analysis, data mining and quantitative real-time RT-PCR approaches,
which showed that RGS2 was expressed in the majority of solid breast
cancers at much higher levels than in normal human mammary cells.CONCLUSION:Molecular
analysis of prospectively isolated mammary epithelial cells identified
RGS2 as a modulator of oxytocin receptor signalling, which is highly
expressed in the myoepithelial cells. The RGS2 gene, but not the
oxytocin receptor, was also shown to be over-expressed in the majority
of breast cancers, identifying the product of this gene, or the pathway(s)
it regulates, as potentially significant therapeutic targets.},
doi = {10.1186/bcr1834},
issn = {1465-5411},
owner = {Meike Kuschel},
pubmedid = {18067675},
timestamp = {2010.04.07},
url = {http://breast-cancer-research.com/content/9/6/R85}
}
@ARTICLE{Smallwood2011,
author = {Smallwood, Heather S. and López-Ferrer, Daniel and Squier, Thomas
C.},
title = {Aging Enhances the Production of Reactive Oxygen Species and Bactericidal
Activity in Peritoneal Macrophages by Upregulating Classical Activation
Pathways},
journal = {Biochemistry},
year = {2011},
volume = {50},
pages = {9911-9922},
number = {45},
abstract = { Maintenance of macrophages in their basal state and their rapid activation
in response to pathogen detection are central to the innate immune
system, acting to limit nonspecific oxidative damage and promote
pathogen killing following infection. To identify possible age-related
alterations in macrophage function, we have assayed the function
of peritoneal macrophages from young (3–4 months) and aged (14–15
months) Balb/c mice. In agreement with prior suggestions, we observe
age-dependent increases in the extent of recruitment of macrophages
into the peritoneum, as well as ex vivo functional changes involving
enhanced nitric oxide production under resting conditions that contribute
to a reduction in the time needed for full activation of senescent
macrophages following exposure to lipopolysaccharides (LPS). Further,
we observe enhanced bactericidal activity following Salmonella uptake
by macrophages isolated from aged Balb/c mice in comparison with
those isolated from young animals. Pathways responsible for observed
phenotypic changes were interrogated using tandem mass spectrometry,
which identified age-dependent increases in levels of proteins linked
to immune cell pathways under basal conditions and following LPS
activation. Immune pathways upregulated in macrophages isolated from
aged mice include proteins critical to the formation of the immunoproteasome.
Detection of these latter proteins is dramatically enhanced following
LPS exposure for macrophages isolated from aged animals; in comparison,
the identification of immunoproteasome subunits is insensitive to
LPS exposure for macrophages isolated from young animals. Consistent
with observed global changes in the proteome, quantitative proteomic
measurements indicate that there are age-dependent abundance changes
involving specific proteins linked to immune cell function under
basal conditions. LPS exposure selectively increases the levels of
many proteins involved in immune cell function in aged Balb/c mice.
Collectively, these results indicate that macrophages isolated from
old mice are in a preactivated state that enhances their sensitivities
to LPS exposure. The hyper-responsive activation of macrophages in
aged animals may act to minimize infection by general bacterial threats
that arise due to age-dependent declines in adaptive immunity. However,
this hypersensitivity and the associated increase in the level of
formation of reactive oxygen species are likely to contribute to
observed age-dependent increases in the level of oxidative damage
that underlie many diseases of the elderly. },
doi = {10.1021/bi2011866},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi2011866},
url = {http://pubs.acs.org/doi/abs/10.1021/bi2011866}
}
@ARTICLE{Smart2011,
author = {Smart, C E and Wronski, A and French, J D and Edwards, S L and Asselin-Labat,
M-L and Waddell, N and Peters, K and Brewster, B L and Brooks, K
and Simpson, K and Manning, N and Lakhani, S R and Grimmond, S and
Lindeman, G J and Visvader, J E and Brown, M A},
title = {Analysis of Brca1-deficient mouse mammary glands reveals reciprocal
regulation of Brca1 and c-kit},
journal = {Oncogene},
year = {2011},
volume = {30},
pages = {1597--1607},
number = {13},
month = mar,
issn = {0950-9232},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/onc.2010.538}
}
@ARTICLE{Smart2010,
author = {Smart, M. and Roden, L.C.},
title = {A small-scale RNA isolation protocol useful for high-throughput extractions
from recalcitrant plants},
journal = {South African Journal of Botany},
year = {2010},
volume = {76},
pages = {375--379},
number = {2},
month = apr,
abstract = {Many plants indigenous to South Africa are rich in secondary and oxidizing
compounds such as pigments, complex polysaccharides and polyphenols.
This makes isolation of high quality RNA for analysis of gene expression
difficult. Here we describe a cost-effective isolation protocol suitable
for RNA extraction from recalcitrant plant species. This method uses
small amounts of tissue, so is useful when material is limited, and
is easy to process large numbers of samples at once. We have used
the method successfully with mature leaves of Protea hybrid [`]Sylvia',
and species P. repens, Leucospermum hybrid [`]Succession', resurrection
plants Xerophyta humilis and Craterostigma pumilum, and mature needles
of Pine (Pinus radiata). RNA was analyzed spectrophotometrically
and was found to be of high purity with low levels of contaminating
compounds. Electrophoretic analyses on denaturing formaldehyde agarose
gels and an Agilent 2100 Bioanalyzer confirmed the presence of RNA
of high integrity. This is the first description of plant RNA integrity
number (RIN) values for these plants using the algorithm designed
for analyses of plant RNA containing multiple ribosomal bands. The
RNA could successfully be used for reverse transcription and gene
amplification.},
issn = {0254-6299},
keywords = {RNA isolation, Gene expression, RIN value, Proteaceae, Pine, Resurrection
plants},
url = {http://www.sciencedirect.com/science/article/B7XN9-4Y9661D-1/2/7bd4899b05548cad11e9c5e80c00311d}
}
@ARTICLE{Smeds2005,
author = {Smeds, J. and Miller, L. D. and Bjohle, J. and Hall, P. and Klaar,
S. and Liu, E. T. and Pawitan, Y. and Ploner, A. and Bergh, J.},
title = {Breast cancer: Gene profile and response to treatment},
journal = {Ann. Onc.},
year = {2005},
volume = {16},
pages = {ii195--202},
number = {suppl_2},
month = jun,
url = {http://annonc.oxfordjournals.org}
}
@ARTICLE{Smeed2010,
author = {Smeed, J.A. and Watkins, C.A. and Gossner, A.G. and Hopkins, J.},
title = {Expression profiling reveals differences in immuno-inflammatory gene
expression between the two disease forms of sheep paratuberculosis},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {135},
pages = {218--225},
number = {3-4},
month = jun,
abstract = {Paratuberculosis is a chronic enteropathy of ruminants caused by Mycobacterium
avium subspecies paratuberculosis (MAP); infection of sheep results
in two disease forms - paucibacillary (tuberculoid) and multibacillary
(lepromatous) associated with the differential polarization of the
immune response. In addition the majority of MAP-infected animals
show no pathology and remain asymptomatic. Microarray and real-time
RT-qPCR analyses were used to compare gene expression in ileum from
sheep with the two disease forms and asymptomatic sheep, to further
understand the molecular basis of the pathologies. Microarrays identified
36 genes with fold-change of >1.5 and P <= 0.05 in at least one comparison;
eight candidates were chosen for RT-qPCR validation. Sequence analysis
of two candidates, CXCR4 and IGFBP6, identified three SNPs in each;
five were found in all three forms of disease and showed no significant
relationship to pathological type. The IGFBP6 G3743 A SNP was not
detected in asymptomatic sheep. The data show that the two forms
of disease are associated with distinct molecular profiles highlighted
by the differential expression of chemokine and chemokine receptor
transcripts, the protein products of which might be implicated in
the different cell infiltrates of the pathologies. The cells within
the lesions also show evidence of abnormal activation; they express
high levels of cytokine transcripts but have reduced expression levels
of transcripts for T cell receptor associated molecules.},
issn = {0165-2427},
keywords = {Mycobacterium avium subsp. paratuberculosis, MAP, Sheep, Chemokines,
Genomics, Pathology},
url = {http://www.sciencedirect.com/science/article/B6TD5-4XVRYHW-2/2/f6dab5bec28cbca0bd62b0596e55a9b8}
}
@ARTICLE{Smeets2008,
author = {Smeets, Pascal J. H. and de Vogel-van den Bosch, Heleen M. and Willemsen,
Peter H. M. and Stassen, Alphons P. and Ayoubi, Torik and van der
Vusse, Ger J. and van Bilsen, Marc},
title = {Transcriptomic analysis of PPAR{alpha}-dependent alterations during
cardiac hypertrophy},
journal = {Physiol Genomics},
year = {2008},
volume = {36},
pages = {15--23},
number = {1},
month = dec,
abstract = {Peroxisome proliferator-activated receptor (PPAR){alpha} regulates
lipid metabolism at the transcriptional level and modulates the expression
of genes involved in inflammation, cell proliferation, and differentiation.
Although PPAR{alpha} has been shown to mitigate cardiac hypertrophy,
knowledge about underlying mechanisms and the nature of signaling
pathways involved is fragmentary and incomplete. The aim of this
study was to identify the processes and signaling pathways regulated
by PPAR{alpha} in hearts challenged by a chronic pressure overload
by means of whole genome transcriptomic analysis. PPAR{alpha}-/-
and wild-type mice were subjected to transverse aortic constriction
(TAC) for 28 days, and left ventricular gene expression profile was
determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing
>45,000 probe sets. In unchallenged hearts, the mere lack of PPAR{alpha}
resulted in 821 differentially expressed genes, many of which are
related to lipid metabolism and immune response. TAC resulted in
a more pronounced cardiac hypertrophy and more extensive changes
in gene expression (1,910 and 312 differentially expressed genes,
respectively) in PPAR{alpha}-/- mice than in wild-type mice. Many
of the hypertrophy-related genes were related to development, signal
transduction, actin filament organization, and collagen synthesis.
Compared with wild-type hypertrophied hearts, PPAR{alpha}-/- hypertrophied
hearts revealed enrichment of gene clusters related to extracellular
matrix remodeling, immune response, oxidative stress, and inflammatory
signaling pathways. The present study therefore demonstrates that,
in addition to lipid metabolism, PPAR{alpha} is an important modulator
of immune and inflammatory response in cardiac muscle.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/36/1/15}
}
@ARTICLE{Smeianov2007,
author = {Smeianov, Vladimir V. and Wechter, Patrick and Broadbent, Jeffery
R. and Hughes, Joanne E. and Rodriguez, Beatriz T. and Christensen,
Tove K. and Ardo, Ylva and Steele, James L.},
title = {Comparative High-Density Microarray Analysis of Gene Expression during
Growth of Lactobacillus helveticus in Milk versus Rich Culture Medium},
journal = {Appl. Envir. Microbiol.},
year = {2007},
volume = {73},
pages = {2661--2672},
number = {8},
month = apr,
abstract = {Lactobacillus helveticus CNRZ32 is used by the dairy industry to modulate
cheese flavor. The compilation of a draft genome sequence for this
strain allowed us to identify and completely sequence 168 genes potentially
important for the growth of this organism in milk or for cheese flavor
development. The primary aim of this study was to investigate the
expression of these genes during growth in milk and MRS medium by
using microarrays. Oligonucleotide probes against each of the completely
sequenced genes were compiled on maskless photolithography-based
DNA microarrays. Additionally, the entire draft genome sequence was
used to produce tiled microarrays in which noninterrupted sequence
contigs were covered by consecutive 24-mer probes and associated
mismatch probe sets. Total RNA isolated from cells grown in skim
milk or in MRS to mid-log phase was used as a template to synthesize
cDNA, followed by Cy3 labeling and hybridization. An analysis of
data from annotated gene probes identified 42 genes that were upregulated
during the growth of CNRZ32 in milk (P < 0.05), and 25 of these genes
showed upregulation after applying Bonferroni's adjustment. The tiled
microarrays identified numerous additional genes that were upregulated
in milk versus MRS. Collectively, array data showed the growth of
CNRZ32 in milk-induced genes encoding cell-envelope proteinases,
oligopeptide transporters, and endopeptidases as well as enzymes
for lactose and cysteine pathways, de novo synthesis, and/or salvage
pathways for purines and pyrimidines and other functions. Genes for
a hypothetical phosphoserine utilization pathway were also differentially
expressed. Preliminary experiments indicate that cheese-derived,
phosphoserine-containing peptides increase growth rates of CNRZ32
in a chemically defined medium. These results suggest that phosphoserine
is used as an energy source during the growth of L. helveticus CNRZ32.},
url = {http://aem.asm.org/cgi/content/abstract/73/8/2661}
}
@ARTICLE{Smejkal2010,
author = {Smejkal, Petr and Szekrényes, �kos and Ryvolová, Markéta and
Foret, František and Guttman, András and Bek, Fritz and Macka,
Mirek},
title = {Chip-based CE for rapid separation of 8-aminopyrene-1,3,6-trisulfonic
acid (APTS) derivatized glycans},
journal = {ELECTROPHORESIS},
year = {2010},
volume = {31},
pages = {3783--3786},
number = {22},
abstract = {Abstract Fluorescently labeled carbohydrates released from glycoproteins
were separated using a commercially available microfluidic chip electrophoresis
system. While the instrumentation was primarily designed for DNA
analysis it was found that the application base can be easily expanded
using the development software provided by the manufacturer. The
carbohydrates were released by enzymatic digestion (PNGase F) from
glycoproteins present in human plasma after boronic acid – lectin
affinity enrichment. After fluorescent labeling with 8-aminopyrene-1,3,6-trisulfonic
acid the carbohydrates were separated based on capillary gel electrophoresis
mechanism and detected by a fluorescence detector using a blue (470 nm)
LED. The separation was completed in 40 s in a microfluidic channel
of 14 mm length. Glucose ladder carbohydrate oligomers differing
by one glucose unit were baseline separated up to a 20-mer with the
main limitation being the detection sensitivity. As expected, the
observed resolution in these experiments did not approach that of
standard CE with 20 times longer separation distance; however, the
chip-based analysis excelled in the speed of the separation. Similar
electrophoretic profiles of glycans released from plasma glycoproteins
were obtained using a standard CE equipment with 35 cm separation
length and microfluidic chips with a separation distance of only
14 mm.},
doi = {10.1002/elps.201000457},
issn = {1522-2683},
keywords = {APTS, Bioanalyzer, Chip-based analysis, Glycans, PSA},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.201000457}
}
@ARTICLE{Smeti2011,
author = {Smeti, Ibtihel and Savary, Etienne and Capelle, Vincent and Hugnot,
Jean Philippe and Uziel, Alain and Zine, Azel},
title = {Expression of candidate markers for stem/progenitor cells in the
inner ears of developing and adult GFAP and nestin promoter-GFP transgenic
mice},
journal = {Gene Expression Patterns},
year = {2011},
volume = {11},
pages = {22--32},
number = {1-2},
month = jan,
abstract = {Loss of hair cells in the mammalian cochlea leads to permanent sensori-neural
hearing loss. Hair cells degenerate and their places are taken by
phalangeal scars formed by non-sensory supporting cells. Current
data indicate that early postnatal post-mitotic supporting cells
can proliferate and differentiate into hair cell-like cells in culture.
In this study, we used GFAP and nestin promoter-GFP transgenic mice
in combination with other stem cell markers to characterize supporting
cell subtypes in the postnatal day-3 (P3) and adult organs of Corti
with potential stem/progenitor cell phenotype. In P3 organ of Corti,
we show GFAP-GFP signal in all the supporting cell subtypes while
the nestin-GFP was restricted to the supporting cells in the inner
hair cell area. At this stage, GFAP and selected stem/progenitor
markers displayed overlapping expression pattern in the supporting
cell population. In the adult, GFAP expression is down-regulated
from the supporting cells in the outer hair cell area and nestin
expression is down-regulated in the supporting cells of the inner
hair cell area. Sox2 and Jagged1 expression is maintained in the
mature supporting cells, while Abcg2 was down-regulated in these
cells. In contrast, GFAP and Abcg2 expression was up-regulated in
the inner sulcus limbal cells outside the mature organ of Corti's
area. Using quantitative reverse transcription-PCR, we found a decrease
in transcripts for Jagged1 and Sox2 in adult cochleae. Our findings
suggest that the loss of regenerative capacity of the adult organ
of Corti is related to down-regulation of stem/progenitor key-markers
from the mature supporting cells.},
issn = {1567-133X},
keywords = {Stem/progenitor cells, Hair cells, Supporting cells, Spiral ganglion,
Organ of Corti, Development},
url = {http://www.sciencedirect.com/science/article/pii/S1567133X10000876}
}
@ARTICLE{Smirnova2008,
author = {Smirnova, Anna S. and Andrade-Oliveira, Vinicius and Gerbase-DeLima,
Maria},
title = {Identification of new splice variants of the genes BAFF and BCMA},
journal = {Molecular Immunology},
year = {2008},
volume = {45},
pages = {1179--1183},
number = {4},
month = feb,
abstract = {The TNF superfamily ligands BAFF and APRIL and receptors BCMA, TACI
and BAFF-R play an important role in the regulation of B cell immunity.
A number of functionally important splice isoforms have already been
characterized for these molecules, stimulating the search for new
transcript variants (TVs). Here we report two new BAFF TVs and three
BCMA TVs, all potentially codifying new proteins. BAFF TVs were expressed
in peripheral blood mononuclear cells (PBMC) of nearly all the individuals
studied, decreasing in level when PBMC were activated by PMA and
ionomycin. They were also detected in PBMC cytoplasmic RNA. Low levels
of the BAFF TVs in all lymphocyte subpopulations analyzed suggest
that their main source in PBMC are monocytes. BCMA TVs were observed
only in some CD19+ cell samples. Functional studies concerning interaction
between isoforms of BAFF, APRIL and their receptors are needed for
elucidation of their significance in the immune response.},
issn = {0161-5890},
keywords = {BAFF, BCMA, TNF superfamily, Alternative splicing, Splice variants},
url = {http://www.sciencedirect.com/science/article/B6T9R-4PKP489-4/2/d440c0c16619b5e1366bc5ec6f68de8a}
}
@ARTICLE{Smirnova2008a,
author = {Smirnova, Anna S. and Ferreira-Silva, Katia C. and Mine, Karina L.
and Andrade-Oliveira, Vinicius and Shulzhenko, Natalia and Gerbase-DeLima,
Maria and Morgun, Andrey},
title = {Differential expression of new LTA splice variants upon lymphocyte
activation},
journal = {Molecular Immunology},
year = {2008},
volume = {45},
pages = {295--300},
number = {1},
month = jan,
abstract = {Lymphotoxin alpha (LTA) is a member of the TNF cytokine superfamily,
produced principally by lymphocytes. It plays an important role in
immune and inflammatory responses. Many TNF superfamily members have
functionally important isoforms generated by alternative splicing
but alternative splicing of LTA has never been studied. The known
LTA protein is encoded by a transcript containing four exons. Here
we report seven new LTA splice variants, three of them evolutionary
conserved. We demonstrate their presence in cytoplasmic RNA suggesting
that they could be translated into new LTA isoforms. We observed
that their expression is differentially regulated upon activation
of peripheral blood mononuclear cells and lymphocyte subpopulations
(CD4+, CD8+, and CD19+). Our data suggest that the new LTA splice
variants might play a role in the regulation of the immune response.},
issn = {0161-5890},
keywords = {Lymphotoxin alpha, Alternative splicing, Splice variants, Lymphocyte
activation, Evolutionary conservation},
url = {http://www.sciencedirect.com/science/article/B6T9R-4NSV0TX-9/2/6b1480b5ed0b285d74263b28063c166e}
}
@ARTICLE{Smirnova2005,
author = {Smirnova, Anna S. and Morgun, Andrey and Shulzhenko, Natalia and
Silva, Ismael D.C.G. and Gerbase-DeLima, Maria},
title = {Identification of new alternative splice events in the TCIRG1 gene
in different human tissues},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {330},
pages = {943--949},
number = {3},
month = may,
abstract = {Two transcript variants (TV) of the T cell immune regulator gene 1
(TCIRG1) have already been characterized. TV1 encodes a subunit of
the osteoclast vacuolar proton pump and TV2 encodes a T cell inhibitory
receptor. Based on the search in dbEST, we validated by RT-PCR six
new alternative splice events in TCIRG1 in most of the 28 human tissues
studied. In addition, we observed that transcripts using the TV1
transcription start site and two splice forms previously described
in a patient with infantile malignant osteopetrosis are also expressed
in various tissues of healthy individuals. Studies of these nine
splice forms in cytoplasmic RNA of peripheral blood mononuclear cells
showed that at least six of them could be efficiently exported from
the nucleus. Since various products with nearly ubiquitous tissue
distribution are generated from TCIRG1, this gene may be involved
in other processes besides immune response and bone resorption.},
issn = {0006-291X},
keywords = {TCIRG1, Alternative splicing, Splice variants, Cytoplasmic RNA, RNA
degradation},
url = {http://www.sciencedirect.com/science/article/B6WBK-4FRB6PP-J/2/f887622ba3266103310eb3d4b4110ff2}
}
@ARTICLE{Smirnova2005a,
author = {Smirnova, Julia B. and Selley, Julian N. and Sanchez-Cabo, Fatima
and Carroll, Kathleen and Eddy, A. Alan and McCarthy, John E. G.
and Hubbard, Simon J. and Pavitt, Graham D. and Grant, Chris M. and
Ashe, Mark P.},
title = {Global Gene Expression Profiling Reveals Widespread yet Distinctive
Translational Responses to Different Eukaryotic Translation Initiation
Factor 2B-Targeting Stress Pathways},
journal = {Mol. Cell. Biol.},
year = {2005},
volume = {25},
pages = {9340--9349},
number = {21},
month = nov,
abstract = {Global inhibition of protein synthesis is a hallmark of many cellular
stress conditions. Even though specific mRNAs defy this (e.g., yeast
GCN4 and mammalian ATF4), the extent and variation of such resistance
remain uncertain. In this study, we have identified yeast mRNAs that
are translationally maintained following either amino acid depletion
or fusel alcohol addition. Both stresses inhibit eukaryotic translation
initiation factor 2B, but via different mechanisms. Using microarray
analysis of polysome and monosome mRNA pools, we demonstrate that
these stress conditions elicit widespread yet distinct translational
reprogramming, identifying a fundamental role for translational control
in the adaptation to environmental stress. These studies also highlight
the complex interplay that exists between different stages in the
gene expression pathway to allow specific preordained programs of
proteome remodeling. For example, many ribosome biogenesis genes
are coregulated at the transcriptional and translational levels following
amino acid starvation. The transcriptional regulation of these genes
has recently been connected to the regulation of cellular proliferation,
and on the basis of our results, the translational control of these
mRNAs should be factored into this equation.},
url = {http://mcb.asm.org/cgi/content/abstract/25/21/9340}
}
@ARTICLE{Smirnova2009,
author = {Smirnova, Natalia P. and Ptitsyn, Andrey A. and Austin, Kathleen
J. and Bielefeldt-Ohmann, Helle and Van Campen, Hana and Han, Hyungchul
and van Olphen, Alberto L. and Hansen, Thomas R.},
title = {Persistent fetal infection with bovine viral diarrhea virus differentially
affects maternal blood cell signal transduction pathways},
journal = {Physiol Genomics},
year = {2009},
volume = {36},
pages = {129--139},
number = {3},
month = feb,
abstract = {The consequences of viral infection during pregnancy include impact
on fetal and maternal immune responses and on fetal development.
Transplacental infection in cattle with noncytopathic bovine viral
diarrhea virus (ncpBVDV) during early gestation results in persistently
infected (PI) fetuses with life-long viremia and susceptibility to
infections. Infection of the fetus during the third trimester or
after birth leads to a transient infection cleared by a competent
immune system. We hypothesized that ncpBVDV infection and presence
of an infected fetus would alter immune response and lead to downregulation
of proinflammatory processes in pregnant dams. Naive pregnant heifers
were challenged with ncpBVDV2 on day 75 (PI fetus) and day 175 [transiently
infected (TI) fetus] or kept uninfected (healthy control fetus).
Maternal blood samples were collected up to day 190 of gestation.
Genome-wide microarray analysis of gene expression in maternal peripheral
white blood cells, performed on days 160 and 190 of gestation, revealed
multiple signal transduction pathways affected by ncpBVDV infection.
Acute infection and presence of a TI fetus caused upregulation of
the type I interferon (IFN) pathway genes, including dsRNA sensors
and IFN-stimulated genes. The presence of a PI fetus caused prolonged
downregulation of chemokine receptor 4 (CXCR4) and T cell receptor
(TCR) signaling in maternal blood cells. We conclude that: 1) infection
with ncpBVDV induces a vigorous type I IFN response, and 2) presence
of a PI fetus causes downregulation of important signaling pathways
in the blood of the dam, which could have deleterious consequences
on fetal development and the immune response.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/36/3/129}
}
@ARTICLE{SmitvanDixhoorn2008,
author = {Smit van Dixhoorn, Mieneke G.A. and Munir, Riffat and Sussman, Garth
and Stad, Robert and de Haan, Muus and van der Hoeven, Tessa and
Rauwerda, Han and Breit, Timo M. and Thallinger, Gerhard G. and Wadee,
Ahmed A.},
title = {Gene expression profiling of suppressor mechanisms in tuberculosis},
journal = {Molecular Immunology},
year = {2008},
volume = {45},
pages = {1573--1586},
number = {6},
month = mar,
abstract = {Mycobacterium tuberculosis (M.tb) infects 8 million and kills 2.2
million people each year worldwide. M.tb modulates the immune response
of the infected individual. Empirically, suppressor carbohydrates
(SC) produced by CD8+ T cells in response to M.tb were found to induce
a T helper 2 response rather than a protective T helper 1 response
in human mononuclear (MN) cells. This study (1) identifies the genes
that modulate the T helper response, (2) describes their function,
and (3) postulates a detailed model for the M.tb infection mechanism.
MN cells from five healthy donors were pulsed with SC and gene expression
profiles of 18,861 genes were assessed in a micro-array experiment.
Twenty-eight genes were found to be increased and 60 genes were decreased
(FDR = 1%, fold change > 1.4) in response to SC. MIP3alpha and platelet
factor 4 (v1) are both significantly enriched (p <= 0.001) in the
GO category "chemokine activity". Repressed genes were significantly
(p <= 0.001) over-represented in the GO terms "response to pathogenic
bacteria", "inflammatory response", "coagulation" and "apoptosis".
Indeed, SC significantly reduced numbers of Annexin V/CD4+ cells,
while inducing hypoproliferation in CD4+ and non-adherent lymphocytes.
This may indicate that M.tb renders a portion of the CD4+ T cell
population unresponsive. Furthermore, validating QRT-PCR analysis
suggests that monocytes provide an immuno-modulatory signal to CD4+
T cells in M.tb infection. These observations will allow development
of new therapeutic interventions to restore the desired T helper
1 response.},
issn = {0161-5890},
keywords = {Human, T cell, Tuberculosis, Micro-array},
url = {http://www.sciencedirect.com/science/article/B6T9R-4RTVCHB-2/2/0466adb8867891a7ca6811e277844e12}
}
@ARTICLE{Smit-McBride2011,
author = {Smit-McBride, Zeljka and Modjtahedi, Sara P. and Cessna, Christopher
T. and Telander, David G. and Hjelmeland, Leonard M. and Morse, Lawrence
S.},
title = {In Vivo Gene Expression Profiling of Retina Postintravitreal Injections
of Dexamethasone and Triamcinolone at Clinically Relevant Time Points
for Patient Care},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {8965-8978},
number = {12},
abstract = {Purpose.To identify retinal genes and their relevant expression pathways
affected by intravitreal injections of dexamethasone (Dex) and triamcinolone
acetonide (TAA) in mice at clinically relevant time points for patient
care. Methods.Differential gene expressions of over 34,000 well-characterized
mouse genes, in the retinas of 6-week-old C57BL/6J mice, were analyzed
after intravitreal steroid injections at 1 week and 1 month time
points, using mouse genome microarrays. The data were analyzed using
commercial microarray analysis software for biologically relevant
changes in gene expression pathways. Results.A common gene pathway,
with differentially activated genes for both steroids and time points,
was "Semaphorin Signaling in Neurons," a member of the "Axonal Guidance
Signaling System." At 1 week postinjection a common theme was activation
of genes expressed in retinal glial cells, tumor necrosis factor-,
and transforming growth factor-{beta} signaling pathways and upregulation
of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide
signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation
of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin
signaling receptor, whereas EphrinB receptor ephexin 1 (Argef15)
was downregulated. Folate signaling appears to be unique for TAA
at 1 week (Folh1, Cubn), whereas aryl-hydrocarbon receptor signaling
might be important for both steroids at 1 month postinjection. Conclusions.Understanding
the molecular and genetic effects of intraocular steroid treatments
is of clinical relevance. This in vivo study has elucidated several
genes and pathways that are potentially altering the neuroprotective/neurodegenerative
balance between glial and retinal ganglion cells during intravitreal
steroid treatment.},
doi = {10.1167/iovs.10-7084},
eprint = {http://www.iovs.org/cgi/reprint/52/12/8965.pdf},
url = {http://www.iovs.org/cgi/content/abstract/52/12/8965}
}
@ARTICLE{Smit-McBride2007,
author = {Smit-McBride, Zeljka and Oltjen, Sharon L. and LaVail, Matthew M.
and Hjelmeland, Leonard M.},
title = {A Strong Genetic Determinant of Hyperoxia-Related Retinal Degeneration
on Mouse Chromosome 6},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {405--411},
number = {1},
month = jan,
abstract = {PURPOSE. Hyperoxia-related retinal degeneration (HRRD) is a model
system in the mouse in which elevated oxygen levels are used to induce
retinal degeneration. The hypothesis for the present study was that
strain differences in HRRD susceptibility are due to allelic variants
of one or more genes in the mouse genome whose human orthologues
should be important targets for research and drug development. METHODS.
C57BL/6J, A/J, or B.A-Chr6 mice were exposed to 75% oxygen (hyperoxia)
or room air for 14 days. After death, one eye was fixed and processed
for outer nuclear layer (ONL) thickness measurements. The retina
and RPE/choroid were separately dissected from the fellow eye and
processed for microarray analysis. Single nucleotide polymorphism
(SNP) analysis for transcribed sequences from the C57BL/6J and A/J
genomes was conducted using the NIH genome site. RESULTS. C57BL/6J
mice developed a significant retinal degeneration in the inferior
hemisphere after 14 days of hyperoxia. Under identical conditions,
A/J mice exhibited only minor changes. A significant genetic effect
was located on chromosome 6. SNP analysis of known transcribed sequences
on chromosome 6 combined with microarray expression analysis yielded
33 candidate genes. CONCLUSIONS. A significant genetic effect of
susceptibility to HRRD is located on chromosome 6. In silico analysis
of transcribed sequences results in a fairly small number of candidate
genes.},
url = {http://www.iovs.org/cgi/content/abstract/48/1/405}
}
@ARTICLE{Smith2006,
author = {Smith, Allen D. and Dawson, Harry},
title = {Glutathione is required for efficient production of infectious picornavirus
virions},
journal = {Virology},
year = {2006},
volume = {353},
pages = {258--267},
number = {2},
month = sep,
abstract = {Glutathione is an intracellular reducing agent that helps maintain
the redox potential of the cell and is important for immune function.
The drug l-buthionine sulfoximine (BSO) selectively inhibits glutathione
synthesis. Glutathione has been reported to block replication of
HIV, HSV-1, and influenza virus, whereas cells treated with BSO exhibit
increased replication of Sendai virus. Pre-treatment of HeLa cell
monolayers with BSO inhibited replication of CVB3, CVB4, and HRV14
with viral titers reduced by approximately 6, 5, and 3 log10, respectively.
The addition of glutathione ethyl ester, but not dithiothreitol or
2-mercaptoethanol, to the culture medium reversed the inhibitory
effect of BSO. Viral RNA and protein synthesis were not inhibited
by BSO treatment. Fractionation of lysates from CVB3-infected BSO-treated
cells on cesium chloride and sucrose gradients revealed that empty
capsids but not mature virions were being produced. The levels of
the 5S and 14S assembly intermediates, however, were not affected
by BSO treatment. These results demonstrate that glutathione is important
for production of mature infectious picornavirus virions.},
issn = {0042-6822},
keywords = {Coxsackievirus B3, Picornavirus, Glutathione, Replication},
url = {http://www.sciencedirect.com/science/article/B6WXR-4KGG5SF-3/2/523a0ff46669de9bac543a4280dae946}
}
@ARTICLE{Smith2011c,
author = {Smith, Aaron G. and Lim, Wen and Pearen, Michael and Muscat, George
E. O. and Sturm, Richard A.},
title = {Regulation of NR4A nuclear receptor expression by oncogenic BRAF
in melanoma cells},
journal = {Pigment Cell \& Melanoma Research},
year = {2011},
volume = {24},
pages = {551--563},
number = {3},
abstract = {Summary Activating mutations in the MAPK pathway effectors, NRAS or
BRAF, are detected in over 70% of melanomas. Accordingly, the identification
of downstream targets of constitutive MAPK signalling in melanoma
represents a major goal in understanding the genesis of this disease.
We report here the regulation of members of the NR4A family of nuclear
receptors by the BRAF-MEK-ERK cascade in melanoma cells. Expression
profiling of melanoma cells in which both the NR4A1 and NR4A2 family
members have been down-regulated by siRNA revealed alterations in
genes associated with proliferation, survival and invasiveness of
tumour cells. Notably, the up-regulation of Wnt/β-catenin pathway
antagonists, DACT1 and CITED1, following NR4A1/2 ablation suggests
a possible link between NR4A and β-catenin activity in melanoma
cells. Taken together, these data suggest that dysregulation of NR4A
nuclear receptors expression and function by the MAPK pathway may
contribute to melanoma tumourigenicity.},
doi = {10.1111/j.1755-148X.2011.00843.x},
issn = {1755-148X},
keywords = {melanoma, nuclear receptor, NR4A, BRAF, beta-catenin},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-148X.2011.00843.x}
}
@ARTICLE{Smith2009,
author = {Smith, Andrew M. and Rahman, Farooq Z. and Hayee, Bu'Hussain and
Graham, Simon J. and Marks, Daniel J.B. and Sewell, Gavin W. and
Palmer, Christine D. and Wilde, Jonathan and Foxwell, Brian M.J.
and Gloger, Israel S. and Sweeting, Trevor and Marsh, Mark and Walker,
Ann P. and Bloom, Stuart L. and Segal, Anthony W.},
title = {Disordered macrophage cytokine secretion underlies impaired acute
inflammation and bacterial clearance in Crohn's disease},
journal = {J. Exp. Med.},
year = {2009},
volume = {206},
pages = {1883--1897},
number = {9},
month = aug,
abstract = {The cause of Crohn's disease (CD) remains poorly understood. Counterintuitively,
these patients possess an impaired acute inflammatory response, which
could result in delayed clearance of bacteria penetrating the lining
of the bowel and predispose to granuloma formation and chronicity.
We tested this hypothesis in human subjects by monitoring responses
to killed Escherichia coli injected subcutaneously into the forearm.
Accumulation of 111In-labeled neutrophils at these sites and clearance
of 32P-labeled bacteria from them were markedly impaired in CD. Locally
increased blood flow and bacterial clearance were dependent on the
numbers of bacteria injected. Secretion of proinflammatory cytokines
by CD macrophages was grossly impaired in response to E. coli or
specific Toll-like receptor agonists. Despite normal levels and stability
of cytokine messenger RNA, intracellular levels of tumor necrosis
factor (TNF) were abnormally low in CD macrophages. Coupled with
reduced secretion, these findings indicate accelerated intracellular
breakdown. Differential transcription profiles identified disease-specific
genes, notably including those encoding proteins involved in vesicle
trafficking. Intracellular destruction of TNF was decreased by inhibitors
of lysosomal function. Together, our findings suggest that in CD
macrophages, an abnormal proportion of cytokines are routed to lysosomes
and degraded rather than being released through the normal secretory
pathway.},
url = {http://jem.rupress.org/cgi/content/abstract/206/9/1883}
}
@ARTICLE{Smith2011a,
author = {Smith, Barry H. and Gazda, Lawrence S. and Conn, Bryan L. and Jain,
Kanti and Asina, Shirin and Levine, Daniel M. and Parker, Thomas
S. and Laramore, Melissa A. and Martis, Prithy C. and Vinerean, Horatiu
V. and David, Eric M. and Qiu, Suizhen and Cordon-Cardo, Carlos and
Hall, Richard D. and Gordon, Bruce R. and Diehl, Carolyn H. and Stenzel,
Kurt H. and Rubin, Albert L.},
title = {Three-Dimensional Culture of Mouse Renal Carcinoma Cells in Agarose
Macrobeads Selects for a Subpopulation of Cells with Cancer Stem
Cell or Cancer Progenitor Properties},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {716--724},
number = {3},
month = feb,
abstract = {The culture of tumor cell lines in three-dimensional scaffolds is
considered to more closely replicate the in vivo tumor microenvironment
than the standard method of two-dimensional cell culture. We hypothesized
that our method of encapsulating and maintaining viable and functional
pancreatic islets in agarose-agarose macrobeads (diameter 6-8 mm)
might provide a novel method for the culture of tumor cell lines.
In this report we describe and characterize tumor colonies that form
within macrobeads seeded with mouse renal adenocarcinoma cells. Approximately
1% of seeded tumor cells survive in the macrobead and over several
months form discrete elliptical colonies appearing as tumor cell
niches with increasing metabolic activity in parallel to colony size.
The tumor colonies demonstrate ongoing cell turnover as shown by
BrdU incorporation and activated caspase-3 and TUNEL staining. Genes
upregulated in the tumor colonies of the macrobead are likely adaptations
to this novel environment, as well as an amplification of G1/S cell-cycle
checkpoints. The data presented, including SCA-1 and Oct4 positivity
and the upregulation of stem cell-like genes such as those associated
with the Wnt pathway, support the notion that the macrobead selects
for a subpopulation of cells with cancer stem cell or cancer progenitor
properties. Cancer Res; 71(3); 716-24. (C)2011 AACR.},
comment = {10.1158/0008-5472.CAN-10-2254},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/3/716}
}
@ARTICLE{Smith2011d,
author = {Smith, Barry H. and Gazda, Lawrence S. and Conn, Bryan L. and Jain,
Kanti and Asina, Shirin and Levine, Daniel M. and Parker, Thomas
S. and Laramore, Melissa A. and Martis, Prithy C. and Vinerean, Horatiu
V. and David, Eric M. and Qiu, Suizhen and North, Alison J. and Couto,
C. Guillermo and Post, Gerald S. and Waters, David J. and Cordon-Cardo,
Carlos and Hall, Richard D. and Gordon, Bruce R. and Diehl, Carolyn
H. and Stenzel, Kurt H. and Rubin, Albert L.},
title = {Hydrophilic Agarose Macrobead Cultures Select for Outgrowth of Carcinoma
Cell Populations That Can Restrict Tumor Growth},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {725--735},
number = {3},
month = feb,
abstract = {Cancer cells and their associated tumors have long been considered
to exhibit unregulated proliferation or growth. However, a substantial
body of evidence indicates that tumor growth is subject to both positive
and negative regulatory controls. Here, we describe a novel property
of tumor growth regulation that is neither species nor tumor-type
specific. This property, functionally a type of feedback control,
is triggered by the encapsulation of neoplastic cells in a growth-restricting
hydrogel composed of an agarose matrix with a second coating of agarose
to form 6- to 8-mm diameter macrobeads. In a mouse cell model of
renal adenocarcinoma (RENCA cells), this process resulted in selection
for a stem cell-like subpopulation which together with at least one
other cell subpopulation drove colony formation in the macrobeads.
Cells in these colonies produced diffusible substances that markedly
inhibited in vitro and in vivo proliferation of epithelial-derived
tumor cells outside the macrobeads. RENCA cells in monolayer culture
that were exposed to RENCA macrobead-conditioned media exhibited
cell-cycle accumulation in S phase due to activation of a G2/M checkpoint.
At least 10 proteins with known tumor suppression functions were
identified by analysis of RENCA macrobead-conditioned media, the
properties of which offer opportunities to further dissect the molecular
basis for tumor growth control. More generally, macrobead culture
may permit the isolation of cancer stem cells and other cells of
the stem cell niche, perhaps providing strategies to define more
effective biologically based clinical approaches to treat neoplastic
disease. Cancer Res; 71(3); 725-35. (C)2011 AACR.},
comment = {10.1158/0008-5472.CAN-10-2258},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/3/725}
}
@ARTICLE{Smith2010b,
author = {Smith, Brennan M. and Bean, Scott R. and Schober, Tilman J. and Tilley,
Michael and Herald, Thomas J. and Aramouni, Fadi},
title = {Composition and Molecular Weight Distribution of Carob Germ Protein
Fractions},
journal = {Journal of Agricultural and Food Chemistry},
year = {2010},
volume = {58},
pages = {7794-7800},
number = {13},
doi = {10.1021/jf101523p},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf101523p},
url = {http://pubs.acs.org/doi/abs/10.1021/jf101523p}
}
@ARTICLE{Smith2005,
author = {Smith, Frances I. and Qu, Qiang and Hong, Seok Jong and Kim, Kwang-Soo
and Gilmartin, Timothy J. and Head, Steven R.},
title = {Gene expression profiling of mouse postnatal cerebellar development
using oligonucleotide microarrays designed to detect differences
in glycoconjugate expression},
journal = {Gene Expression Patterns},
year = {2005},
volume = {5},
pages = {740--749},
number = {6},
month = aug,
abstract = {Differences in gene expression patterns between adult and postnatal
day 7 (P7) mouse cerebellum, at the peak of granule neuron migration,
were analyzed by hybridization to the GLYCOv2 glycogene array. This
custom designed oligonucleotide array focuses on glycosyl transferases,
carbohydrate-binding proteins, proteoglycans and related genes, and
173 genes were identified as being differentially expressed with
statistical confidence. Expression levels for 11 of these genes were
compared by RT-PCR, and their differential expression between P7
and adult cerebellum confirmed. Within the group of genes showing
differential expression, the sialyltransferases (SiaTs) and GalNAc-Ts
that were elevated at P7 prefer glycoprotein substrates, whilst the
SiaTs and GalNAc-Ts that were elevated in the adult preferentially
modify glycolipids, consistent with a role for gangliosides in maintaining
neuronal function in the adult. Also within this group, three proteoglycans--versican,
bamacan and glypican-2--were elevated at P7, along with growth factor
midkine, which is known to bind to multiple types of proteoglycans,
and fibroblast growth factor receptor 1, whose activity is known
to be influenced by heparan sulfate proteoglycans. Two sulfotransferases
that can modify the extent of proteoglycan sulfation were also differentially
regulated, and may modify the interaction of a subset of proteoglycans
with their binding partners during cerebellar development. Bamacan,
glypican-2 and midkine were shown to be expressed in different cell
types, and their roles in cerebellar development during granule neuron
migration and maturation are discussed.},
issn = {1567-133X},
keywords = {Cerebellum, Microarray, Development, Glycoconjugates, Glycosyltransferases,
Proteoglycans, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6W8W-4G94HPD-3/2/d74903eaac58d5151c5ac6052bc28529}
}
@ARTICLE{Smith2008,
author = {Smith, Judith A. and Barnes, Michael D. and Hong, Dihua and DeLay,
Monica L. and Inman, Robert D. and Colbert, Robert A.},
title = {Gene expression analysis of macrophages derived from ankylosing spondylitis
patients reveals interferon-γ dysregulation},
journal = {Arthritis \& Rheumatism},
year = {2008},
volume = {58},
pages = {1640--1649},
number = {6},
abstract = {Abstract 10.1002/art.23512.abs Objective To determine whether macrophages,
a type of cell implicated in the pathogenesis of ankylosing spondylitis
(AS), exhibit a characteristic gene expression pattern. Methods Macrophages
were derived from the peripheral blood of 8 AS patients (median disease
duration 13 years [range <1–43 years]) and 9 healthy control subjects
over 7 days with the use of granulocyte–macrophage colony-stimulating
factor. Cells were stimulated for 24 hours with interferon-γ (IFNγ;
100 units/ml), were left untreated for 24 hours, or were treated
for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated
and examined by microarray and real-time quantitative reverse transcription–polymerase
chain reaction analysis. Results Microarray analysis revealed 198
probe sets detecting the differential expression of 141 unique genes
in untreated macrophages from AS patients compared with healthy controls.
Clustering and principal components analysis clearly distinguished
AS patients and controls. Of the differentially expressed genes,
78 (55%) were IFN-regulated, and their relative expression indicated
a “reverse� IFN signature in AS patient macrophages, where IFNγ–up-regulated
genes were underexpressed and down-regulated genes were overexpressed.
Treatment of macrophages with exogenous IFNγ normalized the expression
of these genes between patients and controls. In addition, the messenger
RNA encoded by the IFNγ gene was ∼2-fold lower in AS patient macrophages
at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018),
as compared with healthy controls. Conclusions Our findings reveal
consistent differences in gene expression in macrophages from AS
patients, with evidence of a striking “reverse� IFN signature.
Together with poor expression and responsiveness of the IFNγ gene,
these results suggest that there may be a relative defect in IFNγ
gene regulation, with autocrine consequences and implications for
disease pathogenesis.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.23512}
}
@ARTICLE{Smith2011b,
author = {Smith, Jacqueline and Sadeyen, Jean-Remy and Paton, Ian R. and Hocking,
Paul M. and Salmon, Nigel and Fife, Mark and Nair, Venugopal and
Burt, David W. and Kaiser, Pete},
title = {Systems Analysis of Immune Responses in Marek's Disease Virus-Infected
Chickens Identifies a Gene Involved in Susceptibility and Highlights
a Possible Novel Pathogenicity Mechanism},
journal = {J. Virol.},
year = {2011},
volume = {85},
pages = {11146-11158},
number = {21},
abstract = {Marek's disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus
that causes disease that is both a cancer model and a continuing
threat to the world's poultry industry. This comprehensive gene expression
study analyzes the host response to infection in both resistant and
susceptible lines of chickens and inherent expression differences
between the two lines following the infection of the host. A novel
pathogenicity mechanism, involving the downregulation of genes containing
HIC1 transcription factor binding sites as early as 4 days postinfection,
was suggested from this analysis. HIC1 drives antitumor mechanisms,
suggesting that MDV infection switches off genes involved in antitumor
regulation several days before the expression of the MDV oncogene
meq. The comparison of the gene expression data to previous QTL data
identified several genes as candidates for involvement in resistance
to MD. One of these genes, IRG1, was confirmed by single nucleotide
polymorphism analysis to be involved in susceptibility. Its precise
mechanism remains to be elucidated, although the analysis of gene
expression data suggests it has a role in apoptosis. Understanding
which genes are involved in susceptibility/resistance to MD and defining
the pathological mechanisms of the disease gives us a much greater
ability to try to reduce the incidence of this virus, which is costly
to the poultry industry in terms of both animal welfare and economics.},
doi = {10.1128/JVI.05499-11},
eprint = {http://jvi.asm.org/cgi/reprint/85/21/11146.pdf},
url = {http://jvi.asm.org/cgi/content/abstract/85/21/11146}
}
@ARTICLE{Smith2010a,
author = {Smith, Karen and Gould, Katherine A. and Ramage, Gordon and Gemmell,
Curtis G. and Hinds, Jason and Lang, Sue},
title = {Influence of Tigecycline on Expression of Virulence Factors in Biofilm-Associated
Cells of Methicillin-Resistant Staphylococcus aureus},
journal = {Antimicrob. Agents Chemother.},
year = {2010},
volume = {54},
pages = {380--387},
number = {1},
month = jan,
abstract = {Methicillin-resistant Staphylococcus aureus (MRSA) infections are
complicated by the ability of the organism to grow in surface-adhered
biofilms on a multitude of abiotic and biological surfaces. These
multicellular communities are notoriously difficult to eradicate
with antimicrobial therapy. Cells within the biofilm may be exposed
to a sublethal concentration of the antimicrobial due to the metabolic
and phenotypic diversity of the biofilm-associated cells or the protection
offered by the biofilm structure. In the present study, the influence
of a sublethal concentration of tigecycline on biofilms formed by
an epidemic MRSA-16 isolate was investigated by transcriptome analysis.
In the presence of the drug, 309 genes were upregulated and 213 genes
were downregulated by more than twofold in comparison to the levels
of gene regulation detected for the controls not grown in the presence
of the drug. Microarray data were validated by real-time reverse
transcription-PCR and phenotypic assays. Tigecycline altered the
expression of a number of genes encoding proteins considered to be
crucial for the virulence of S. aureus. These included the reduced
expression of icaC, which is involved in polysaccharide intercellular
adhesin production and biofilm development; the upregulation of fnbA,
clfB, and cna, which encode adhesins which attach to human proteins;
and the downregulation of the cap genes, which mediate the synthesis
of the capsule polysaccharide. The expression of tst, which encodes
toxic shock syndrome toxin 1 (TSST-1), was also significantly reduced;
and an assay performed to quantify TSST-1 showed that the level of
toxin production by cells treated with tigecycline decreased by 10-fold
(P < 0.001) compared to the level of production by untreated control
cells. This study suggests that tigecycline may reduce the expression
of important virulence factors in S. aureus and supports further
investigation to determine whether it could be a useful adjunct to
therapy for the treatment of biofilm-mediated infections.},
url = {http://aac.asm.org/cgi/content/abstract/54/1/380}
}
@ARTICLE{Smith2012,
author = {Karen L. Smith and Bruce Herron and Natalie Dowell-Mesfin and Hong
Wu and Sung June Kim and William Shain and Matthew R. Hynd},
title = {Knockdown of cortical transthyretin expression around implanted neural
prosthetic devices using intraventricular siRNA injection in the
brain},
journal = {Journal of Neuroscience Methods},
year = {2012},
volume = {203},
pages = {398 - 406},
number = {2},
abstract = {Neural prosthetic devices are showing increasing clinical use for
the treatment of a variety of neurological disorders. However the
functions on these devices are often limited due to an inability
to effectively and chronically interface with neural tissue. The
insertion of devices has been shown to result in significant cellular
and vascular trauma surrounding the insertion site. In particular,
the up-regulation of genes involved in neuronal degeneration are
believed to contribute to the loss of neuronal tissue. RNA interference
is a novel technique for the development of antisense therapeutics
for the post-transcriptional silencing of specific genes. In order
to demonstrate the feasibility of RNA interference for gene-specific
silencing in vivo, a short interfering RNA targeting transthyretin,
was infused prior to unilateral device insertion. Injection of siRNA
was found to significantly reduce the expression of transthyretin
mRNA when expression was assessed at 1 week following device insertion.
Concomitant decreases in transthyretin protein levels were also observed.
These data demonstrate the feasibility of using RNA interference
to modulate the initial reactive cellular responses that occur in
the brain following insertion of neural prosthetic devices.},
doi = {10.1016/j.jneumeth.2011.09.023},
issn = {0165-0270},
keywords = {RNA interference},
url = {http://www.sciencedirect.com/science/article/pii/S0165027011005711}
}
@ARTICLE{Smith2003,
author = {Smith, Lee and Underhill, Peter and Pritchard, Clare and Tymowska-Lalanne,
Zuzanna and Abdul-Hussein, Saba and Hilton, Helen and Winchester,
Laura and Williams, Deborah and Freeman, Tom and Webb, Sarah and
Greenfield, Andy},
title = {Single primer amplification (SPA) of cDNA for microarray expression
analysis},
journal = {Nucleic Acids Res.},
year = {2003},
volume = {31},
pages = {e9--},
number = {3},
month = feb,
abstract = {The potential of expression analysis using cDNA microarrays to address
complex problems in a wide variety of biological contexts is now
being realised. A limiting factor in such analyses is often the amount
of RNA required, usually tens of micrograms. To address this problem
researchers have turned to methods of improving detection sensitivity,
either through increasing fluorescent signal output per mRNA molecule
or increasing the amount of target available for labelling by use
of an amplification procedure. We present a novel DNA-based method
in which an oligonucleotide is incorporated into the 3' end of cDNA
during second-strand cDNA synthesis. This sequence provides an annealing
site for a single complementary heel primer that directs Taq DNA
polymerase amplification of cDNA following multiple cycles of denaturation,
annealing and extension. The utility of this technique for transcriptome-wide
screening of relative expression levels was compared to two alternative
methodologies for production of labelled cDNA target, namely incorporation
of fluorescent nucleotides by reverse transcriptase or the Klenow
fragment. Labelled targets from two distinct mouse tissues, adult
liver and kidney, were compared by hybridisation to a set of cDNA
microarrays containing 6500 mouse cDNA probes. Here we demonstrate,
through a dilution series of cDNA derived from 10 {micro}g of total
RNA, that it is possible to produce datasets comparable to those
produced with unamplified targets with the equivalent of 30 ng of
total RNA. The utility of this technique for microarray analysis
in cases where sample is limited is discussed.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/31/3/e9}
}
@ARTICLE{Smith2007,
author = {Smith, Laura D. and Hickman, Emma S. and Parry, Richard V. and Westwick,
John and Ward, Stephen G.},
title = {PI3K[gamma] is the dominant isoform involved in migratory responses
of human T lymphocytes: Effects of ex vivo maintenance and limitations
of non-viral delivery of siRNA},
journal = {Cellular Signalling},
year = {2007},
volume = {19},
pages = {2528--2539},
number = {12},
month = dec,
abstract = {Use of mice in which individual PI3K isoforms have been deleted or
mutated by gene targeting, has determined that PI3K[gamma] provides
a key migratory signal for T lymphocyte migration. Since PI3K[gamma]
can be a dispensable signal for directional migration of human T
cells, we have adopted a pharmacological and siRNA strategy to assess
the contribution of individual PI3K isoforms to chemokine-stimulated
migration of human T cells. The broad spectrum PI3K isoform inhibitor
Ly294002 inhibits CXCL12-stimulated migration of freshly isolated
T lymphocytes. Use of second generation inhibitors that can discriminate
between individual PI3K isoforms, revealed that PI3K[gamma] was the
major contributor to CXCL12-induced migration and PI3K/Akt signaling
(as assessed by S6 phosphorylation). Non-viral delivery of siRNA
targeting class I (PI3K[gamma]), class II (PI3KC2[alpha] and PI3KC2[beta])
and class III PI3Ks, followed by 3 days ex vivo culture, reduces
the levels of isoform mRNA, but is insufficient to impact on cell
migration responses. However, ex vivo maintenance of T cells alone,
independently of siRNA treatment, resulted in the migratory response
of T cells toward CXCL12 becoming insensitive to Ly294002. Remarkably,
random migration remains sensitive to Ly294002. This study therefore,
highlights that the migratory response of freshly isolated human
T cells is dependent on PI3K signals that are provided predominantly
by PI3K[gamma]. However, the role of PI3K in cell migration is context-dependent
and diminishes during ex vivo maintenance.},
issn = {0898-6568},
keywords = {T cells, Chemokines, Cell trafficking, Inflammation, Signal transduction},
url = {http://www.sciencedirect.com/science/article/B6T2M-4PGGP3H-1/2/c690392fc0bd5f97db4067bbd517cdf9}
}
@ARTICLE{Smith2010,
author = {Smith, Latasha M. and Yao-Borengasser, Aiwei and Starks, Tasha and
Tripputi, Mark and Kern, Philip A. and Rasouli, Neda},
title = {Insulin Resistance in African-American and Caucasian Women: Differences
in Lipotoxicity, Adipokines, and Gene Expression in Adipose Tissue
and Muscle},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {4441--4448},
number = {9},
month = sep,
abstract = {Objectives: We tested whether African-American (AA) women are different
from Caucasian women in regard to lipotoxicity, adipokines, and gene
expression in adipose tissue and muscle. Design: Insulin sensitivity
(SI), plasma adipocytokine levels, intramyocellular lipid (IMCL),
and the expression of candidate genes in adipose tissue and muscle
were measured in AA and Caucasian women. Setting: This study was
performed in an ambulatory general clinical research center. Subjects:
Subjects were healthy, nondiabetic AA and Caucasian women. Interventions:
There were no interventions. Main Outcome Measures: Comparison of
SI, IMCL, plasma adiponectin, and the expression of candidate genes
regulating adipogenesis, lipogenesis, and inflammation in adipose
tissue and muscle. Results: AA had lower plasma adiponectin and IMCL
when compared with Caucasian women with similar SI. In sc adipose
tissue (SAT), the expression of genes involved in adipogenesis including
peroxisomal proliferator-activated receptor-{gamma} (PPAR{gamma})
and lipin-1{beta} were also reduced in SAT of AA subjects (19%, P
= 0.06, and 25%, P = 0.05, respectively). Similarly, 1-acylglycerol-3-phosphate
acyltransferase 2 (AGPAT 2), stearoyl-coenzyme A desaturase-1 (SCD1),
and CD36 mRNA expression was significantly reduced in SAT by 19,
54, and 28% respectively (P < 0.01 for all) in AA compared with Caucasian
women. Yet the expression of CD68 in SAT was similar in both ethnic
groups. Gene expression studies in muscle revealed a 31% reduction
in expression of AGPAT 2 and a 72% reduction in SCD1 genes in AA.
Conclusion: AA women demonstrated lower expression of several PPAR{gamma}-responsive
genes in adipose tissue, lower plasma adiponectin, and decreased
IMCL levels as compared with Caucasians, which suggests that African-Americans
may be protected from lipotoxicity. Together these data suggest significant
ethnic differences in the pathophysiology of insulin resistance.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/9/4441}
}
@ARTICLE{Smith2009a,
author = {Smith, Lincoln S and Gharib, Sina A and Frevert, Charles W and Martin,
Thomas R},
title = {Effects of Age on the Synergistic Interactions between Lipopolysaccharide
and Mechanical Ventilation in Mice},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2009},
volume = {Epub},
pages = {2009-0039OC--},
month = nov,
abstract = {Rationale. Children have a lower incidence and mortality from acute
lung injury than adults, and infections are the most common event
associated with acute lung injury (ALI). Objectives. To study the
effects of age on susceptibility to ALI, we investigated the responses
to microbial products combined with mechanical ventilation in juvenile
(21 day) and adult (16 week-old) mice. Methods. Juvenile and adult
C57BL/6 mice were treated with inhaled E. coli 0111:B4 lipopolysaccharide
(LPS), then mechanical ventilation using tidal volume = 15 mL/kg.
Comparison groups included mice treated with LPS or mechanical ventilation
alone, and untreated age-matched controls. Measurements and Main
Results. In adult animals treated for 3 hr, LPS plus mechanical ventilation
caused synergistic increases in neutrophils (p < 0.01) and IgM in
bronchoalveolar lavage fluid (p = 0.03), and IL-1{beta} in whole
lung homogenates (p < 0.01) as compared with either modality alone.
Although juvenile and adult mice had similar responses to either
LPS or mechanical ventilation alone, the synergistic interactions
between LPS and mechanical ventilation did not occur in juvenile
mice. Computational analysis of gene expression array data suggest
that the acquisition of synergy with increasing age results, in part,
from the loss of anti-apoptotic responses, and the acquisition of
pro-inflammatory responses to the combination of LPS and mechanical
ventilation. Conclusions. These data suggest that the synergistic
inflammatory and injury responses to inhaled LPS combined with mechanical
ventilation are acquired with age as a result of coordinated changes
in gene expression of inflammatory, apoptotic, and TGF{beta} pathways.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/2009-0039OCv1}
}
@ARTICLE{Smith2006a,
author = {Smith, Laura T. and Lin, Mauting and Brena, Romulo M. and Lang, James
C. and Schuller, David E. and Otterson, Gregory A. and Morrison,
Carl D. and Smiraglia, Dominic J. and Plass, Christoph},
title = {Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24
in lung and head and neck cancer},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {982--987},
number = {4},
month = jan,
abstract = {The identification of tumor suppressor genes has classically depended
on their localization within recurrent regions of loss of heterozygosity.
According to Knudson's two-hit hypothesis, the remaining allele is
lost, either genetically or, more recently identified, through epigenetic
events. To date, retrospective analyses have determined promoter
methylation as a common alternative alteration in cancer cells to
silence cancer-related genes. Here we report an application of restriction
landmark genomic scanning that allows for DNA methylation profiling
along a region of recurrent loss of heterozygosity at chromosome
6q23-q24. This approach resulted in the identification of a tumor
suppressor gene, TCF21, which is frequently lost in human malignancies.
We demonstrate that TCF21 is expressed in normal lung airway epithelial
cells and aberrantly methylated and silenced in the majority of head
and neck squamous cell carcinomas and non-small-cell lung cancers
analyzed. TCF21 is known to regulate mesenchymal cell transition
into epithelial cells, a property that has been shown to be deficient
in carcinomas. We further demonstrate that exogenous expression of
TCF21 in cells that have silenced the endogenous TCF21 locus resulted
in a reduction of tumor properties in vitro and in vivo.},
url = {http://www.pnas.org/cgi/content/abstract/103/4/982}
}
@ARTICLE{Smith2005a,
author = {Smith, M. J. and Jeddeloh, J. A.},
title = {DNA Methylation in Lysogens of Pathogenic Burkholderia spp. Requires
Prophage Induction and Is Restricted to Excised Phage DNA},
journal = {J. Bacteriol.},
year = {2005},
volume = {187},
pages = {1196--1200},
number = {3},
month = feb,
abstract = {Burkholderia mallei-specific phage {Phi}E125 encodes DNA methyltransferases
in both the lysogenic and replication modules within its genome.
Characterization of DNA methylation in recombinant systems, specifically
in {Phi}E125 lysogenic strains of B. mallei and Burkholderia thailandensis,
revealed that, upon induction, cytosine methylation was targeted
specifically to the phage episome but not the phage provirus or the
host chromosome.},
url = {http://jb.asm.org/cgi/content/abstract/187/3/1196}
}
@ARTICLE{Smith2006b,
author = {Smith, Maria W. and Walters, Kathie-Anne and Korth, Marcus J. and
Fitzgibbon, Matthew and Proll, Sean and Thompson, Jill C. and Yeh,
Matthew M. and Shuhart, Margaret C. and Furlong, Jeffrey C. and Cox,
Paula P. and Thomas, David L. and Phillips, John D. and Kushner,
James P. and Fausto, Nelson and Carithers, Jr, Robert L. and Katze,
Michael G.},
title = {Gene Expression Patterns That Correlate With Hepatitis C and Early
Progression to Fibrosis in Liver Transplant Recipients},
journal = {Gastroenterology},
year = {2006},
volume = {130},
pages = {179--187},
number = {1},
month = jan,
abstract = {Background & Aims: Liver transplant recipients infected with hepatitis
C virus (HCV) develop recurrent hepatitis soon after transplantation
and, in some cases, progress to fibrosis within the first 2 years.
Our goals were to identify molecular processes influencing the liver
disease progression and to find potential gene markers of early fibrosis.
Methods: We performed gene expression profiling on serial liver biopsy
specimens obtained from 13 (11 infected and 2 uninfected) transplant
recipients within the first year after transplantation at 0, 3, 6,
and 12 months. The data were compared with clinical observations
and with a gene expression database obtained for 55 nontransplant
HCV-infected and uninfected liver samples. Results: We identified
several specific gene expression patterns. The first pattern was
unique for the transplant recipients regardless of their infection
status. The corresponding genes encoded stress response proteins
and blood proteins involved in coagulation that were differentially
expressed in response to posttransplantation graft recovery. The
second pattern was specific to HCV-infected samples and included
up-regulation of genes encoding components of the interferon-mediated
antiviral response and immune system (antigen presentation, cytotoxic
response). This up-regulation pattern was absent or suppressed in
the patients who developed early fibrosis, indicating that the disease
progression might result from an impaired liver response to infection.
Finally, we identified gene expression patterns that were specific
for 12-month biopsy specimens in all 4 HCV-infected patients who
developed early fibrosis. Conclusions: The identified gene expression
patterns may prove useful for diagnostic and prognostic applications
in HCV-infected patients, including predicting early progression
to fibrosis.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4J08C1C-1B/2/6f8190bd32b610d528e1b21b2f54b6f6}
}
@ARTICLE{Smith2003a,
author = {Smith, Maria W. and Yue, Zhaoxia N. and Geiss, Gary K. and Sadovnikova,
Natalya Y. and Carter, Victoria S. and Boix, Loreto and Lazaro, Catherine
A. and Rosenberg, Gary B. and Bumgarner, Roger E. and Fausto, Nelson
and Bruix, Jordi and Katze, Michael G.},
title = {Identification of Novel Tumor Markers in Hepatitis C Virus-associated
Hepatocellular Carcinoma},
journal = {Cancer Res.},
year = {2003},
volume = {63},
pages = {859--864},
number = {4},
month = feb,
abstract = {Hepatocellular carcinoma (HCC) is a common primary cancer associated
frequently with hepatitis C virus (HCV). To gain insight into the
molecular mechanisms of hepatocarcinogenesis, and to identify potential
HCC markers, we performed cDNA microarray analysis on surgical liver
samples from 20 HCV-infected patients. RNA from individual tumors
was compared with RNA isolated from adjacent nontumor tissue that
was cirrhotic in all of the cases. Gene expression changes related
to cirrhosis were filtered out using experiments in which pooled
RNA from HCV-infected cirrhotic liver without tumors was compared
with pooled RNA from normal liver. Expression of [~]13,600 genes
was analyzed using the advanced analysis tools of the Rosetta Resolver
System. This analysis revealed a set of 50 potential HCC marker genes,
which were up-regulated in the majority of the tumors analyzed, much
more widely than common clinical markers such as cell proliferation-related
genes. This HCC marker set contained several cancer-related genes,
including serine/threonine kinase 15 (STK15), which has been implicated
in chromosome segregation abnormalities but which has not been linked
previously with liver cancer. In addition, a set of genes encoding
secreted or plasma proteins was identified, including plasma glutamate
carboxypeptidase (PGCP) and two secreted phospholipases A2 (PLA2G13
and PLA2G7). These genes may provide potential HCC serological markers
because of their strong up-regulation in more than half of the tumors
analyzed. Thus, high throughput methods coupled with high-order statistical
analyses may result in the development of new diagnostic tools for
liver malignancies.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/63/4/859}
}
@ARTICLE{Smith2003b,
author = {Smith, Maria W. and Yue, Zhaoxia N. and Korth, Marcus J. and Do,
Hao A. and Boix, Loreto and Fausto, Nelson and Bruix, Jordi and Carithers,
Robert L. and Katze, Michael G.},
title = {Hepatitis C virus and liver disease: Global transcriptional profiling
and identification of potential markers},
journal = {Hepatology},
year = {2003},
volume = {38},
pages = {1458--1467},
number = {6},
abstract = {Abstract 10.1002/hep.510380619.abs Microarray analysis of RNA from
hepatitis C virus (HCV)-infected cirrhotic livers was performed to
identify a gene expression signature of liver disease. The expression
levels of approximately 13,600 genes were analyzed using surgical
material and core biopsy specimens from HCV-infected cirrhotic liver
explants in comparison with reference samples of normal nondiseased
liver. In addition, normal liver samples were compared with each
other to determine normal physiologic variation in gene expression.
A set of genes, including some associated with stress, acute-phase
immune response, and hepatic stellate cell activation, had variable
expression levels in normal livers. These genes were subtracted from
the sets of genes differentially expressed in cirrhotic livers. To
exclude cancer-related genes from our marker sets, we subtracted
genes that also were expressed differentially in hepatocellular carcinomas.
The resultant HCV- and liver disease-associated gene set provided
a molecular portrait of several processes occurring in the HCV-infected
liver. It included (1) genes expressed in activated lymphocytes infiltrating
the cirrhotic liver, and activated liver macrophages; (2) genes involved
in remodeling of extracellular matrix-cell and cell-cell interactions
associated with cytoskeleton rearrangements; (3) genes related to
the anti-apoptotic pathway of Bcl-2 signaling; and (4) genes involved
with the interferon response and virus-host interactions. In conclusion,
our microarray analysis identified several potential gene markers
of HCV-associated liver disease and contributed to our rapidly expanding
database of experiments describing HCV pathogenesis.},
issn = {1527-3350},
publisher = {W.B. Saunders},
url = {http://dx.doi.org/10.1016/j.hep.2003.09.024}
}
@ARTICLE{Smith2007a,
author = {Smith, O.P.Milling and Jabbour, H.N. and Critchley, H.O.D.},
title = {Cyclooxygenase enzyme expression and E series prostaglandin receptor
signalling are enhanced in heavy menstruation},
journal = {Hum. Reprod.},
year = {2007},
volume = {22},
pages = {1450--1456},
number = {5},
month = may,
abstract = {BACKGROUNDAlthough the mechanisms underlying the causes of heavy menstrual
blood loss (MBL) remain to be elucidated, prostaglandins have been
previously implicated. This study was initiated to elucidate a pattern
of expression of the various components of the cyclooxygenase (COX)-prostaglandin
signalling pathways present in the endometrium of women with normal
and heavy MBLs. METHODSEndometrial biopsies were collected at different
stages of the menstrual cycle from women who underwent measurement
of MBL. Tissue was divided for either examination of gene expression
by quantitative RT-PCR analysis or in vitro culture experimentation.
RESULTSAnalysis of gene expression demonstrated a significant elevation
in expression of COX-1 and COX-2 mRNA in endometrium obtained from
women with heavy MBL when compared with endometrium obtained from
women with normal MBL. Tissue culture with PGE2 stimulation caused
a significantly elevated production of cyclic AMP (cAMP) by endometrium
of women with heavy MBL when compared with normal MBL. Expression
of phosphodiesterase 4B, an enzyme involved in cAMP breakdown, was
reduced in these same endometrial samples obtained from women with
heavy MBL. CONCLUSIONSThese data identify the E series prostaglandin
receptors and their signalling pathways as potential therapeutic
targets in the treatment of heavy menstruation.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/22/5/1450}
}
@ARTICLE{Smith2008a,
author = {Smith, Pamela D. and Brett, Suzanne E. and Luykenaar, Kevin D. and
Sandow, Shaun L. and Marrelli, Sean P. and Vigmond, Edward J. and
Welsh, Donald G.},
title = {KIR channels function as electrical amplifiers in rat vascular smooth
muscle},
journal = {J. Physiol.},
year = {2008},
volume = {586},
pages = {1147--1160},
number = {4},
month = feb,
abstract = {Strong inward rectifying K+ (KIR) channels have been observed in vascular
smooth muscle and can display negative slope conductance. In principle,
this biophysical characteristic could enable KIR channels to amplify'
responses initiated by other K+ conductances. To test this, we have
characterized the diversity of smooth muscle KIR properties in resistance
arteries, confirmed the presence of negative slope conductance and
then determined whether KIR inhibition alters the responsiveness
of middle cerebral, coronary septal and third-order mesenteric arteries
to K+ channel activators. Our initial characterization revealed that
smooth muscle KIR channels were highly expressed in cerebral and
coronary, but not mesenteric arteries. These channels comprised KIR2.1
and 2.2 subunits and electrophysiological recordings demonstrated
that they display negative slope conductance. Computational modelling
predicted that a KIR-like current could amplify the hyperpolarization
and dilatation initiated by a vascular K+ conductance. This prediction
was consistent with experimental observations which showed that 30
{micro}M Ba2+ attenuated the ability of K+ channel activators to
dilate cerebral and coronary arteries. This attenuation was absent
in mesenteric arteries where smooth muscle KIR channels were poorly
expressed. In summary, smooth muscle KIR expression varies among
resistance arteries and when channel are expressed, their negative
slope conductance amplifies responses initiated by smooth muscle
and endothelial K+ conductances. These findings highlight the fact
that the subtle biophysical properties of KIR have a substantive,
albeit indirect, role in enabling agonists to alter the electrical
state of a multilayered artery.},
url = {http://jp.physoc.org/cgi/content/abstract/586/4/1147}
}
@ARTICLE{Smith2007b,
author = {Smith, Stephen E. P. and Li, Jennifer and Garbett, Krassimira and
Mirnics, Karoly and Patterson, Paul H.},
title = {Maternal Immune Activation Alters Fetal Brain Development through
Interleukin-6},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {10695--10702},
number = {40},
month = oct,
abstract = {Schizophrenia and autism are thought to result from the interaction
between a susceptibility genotype and environmental risk factors.
The offspring of women who experience infection while pregnant have
an increased risk for these disorders. Maternal immune activation
(MIA) in pregnant rodents produces offspring with abnormalities in
behavior, histology, and gene expression that are reminiscent of
schizophrenia and autism, making MIA a useful model of the disorders.
However, the mechanism by which MIA causes long-term behavioral deficits
in the offspring is unknown. Here we show that the cytokine interleukin-6
(IL-6) is critical for mediating the behavioral and transcriptional
changes in the offspring. A single maternal injection of IL-6 on
day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and
latent inhibition (LI) deficits in the adult offspring. Moreover,
coadministration of an anti-IL-6 antibody in the poly(I:C) model
of MIA prevents the PPI, LI, and exploratory and social deficits
caused by poly(I:C) and normalizes the associated changes in gene
expression in the brains of adult offspring. Finally, MIA in IL-6
knock-out mice does not result in several of the behavioral changes
seen in the offspring of wild-type mice after MIA. The identification
of IL-6 as a key intermediary should aid in the molecular dissection
of the pathways whereby MIA alters fetal brain development, which
can shed new light on the pathophysiological mechanisms that predispose
to schizophrenia and autism.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/40/10695}
}
@ARTICLE{Smith2011,
author = {Smith, Susan M. E. and Morgan, Deri and Musset, Boris and Cherny,
Vladimir V. and Place, Allen R. and Hastings, J. Woodland and DeCoursey,
Thomas E.},
title = {Voltage-gated proton channel in a dinoflagellate},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {18162-18167},
number = {44},
abstract = {Fogel and Hastings first hypothesized the existence of voltage-gated
proton channels in 1972 in bioluminescent dinoflagellates, where
they were thought to trigger the flash by activating luciferase.
Proton channel genes were subsequently identified in human, mouse,
and Ciona intestinalis, but their existence in dinoflagellates remained
unconfirmed. We identified a candidate proton channel gene from a
Karlodinium veneficum cDNA library based on homology with known proton
channel genes. K. veneficum is a predatory, nonbioluminescent dinoflagellate
that produces toxins responsible for fish kills worldwide. Patch
clamp studies on the heterologously expressed gene confirm that it
codes for a genuine voltage-gated proton channel, kHV1: it is proton-specific
and activated by depolarization, its gH-V relationship shifts with
changes in external or internal pH, and mutation of the selectivity
filter (which we identify as Asp51) results in loss of proton-specific
conduction. Indirect evidence suggests that kHV1 is monomeric, unlike
other proton channels. Furthermore, kHV1 differs from all known proton
channels in activating well negative to the Nernst potential for
protons, EH. This unique voltage dependence makes the dinoflagellate
proton channel ideally suited to mediate the proton influx postulated
to trigger bioluminescence. In contrast to vertebrate proton channels,
whose main function is acid extrusion, we propose that proton channels
in dinoflagellates have fundamentally different functions of signaling
and excitability.},
doi = {10.1073/pnas.1115405108},
eprint = {http://www.pnas.org/cgi/reprint/108/44/18162.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/44/18162}
}
@ARTICLE{Smith2006c,
author = {Smith, Tim A.D. and Sharma, Rituka I. and Thompson, Alastair M. and
Paulin, Fiona E.M.},
title = {Tumor 18F-FDG Incorporation Is Enhanced by Attenuation of P53 Function
in Breast Cancer Cells In Vitro},
journal = {J. Nucl. Med.},
year = {2006},
volume = {47},
pages = {1525--1530},
number = {9},
month = sep,
abstract = {Mutations in the p53 gene, often resulting in loss of wild-type (WT)
p53 expression, are found at high frequencies in several cancer types.
High uptake of 18F-FDG detected using 18F-FDG PET has been associated
with a poor prognosis. To determine whether high 18F-FDG uptake may
be related to decreased expression of WT p53, we examined 18F-FDG
uptake in cells transfected with dominant negative p53 constructs
that abrogate WT p53 function. Methods: Two clones of MCF-7 breast
cancer cells were stably transfected with a dominant negative p53
construct. 18F-FDG uptake, hexokinase (HK) activity, and glucose
transport were measured in each clone and in the control WT cells
from which the clones had been derived. The expression of glucose
transporters, HKs, and glucose-6-phosphatase was determined using
microarray technology. Results: Microarray experiments revealed that
glucose transporters 1, 8, and 10 were expressed in MCF-7 cells,
whereas glucose-6-phosphatase was absent. HK I was the principal
HK in MCF-7 cells but was not differentially expressed at the messenger
RNA level in the dominant negative p53 clones, compared with WT cells.
However, increased HK activity was observed in both dominant negative
p53 clones, compared with WT MCF-7. 18F-FDG uptake was increased
in both clones expressing the dominant negative p53 constructs. Conclusion:
These data suggest that abrogation of p53 in breast cancer is associated
with specific changes in glucose metabolism detected by PET.},
url = {http://jnm.snmjournals.org/cgi/content/abstract/47/9/1525}
}
@ARTICLE{Smits2005,
author = {Smits, Wiep Klaas and Dubois, Jean-Yves F. and Bron, Sierd and van
Dijl, Jan Maarten and Kuipers, Oscar P.},
title = {Tricksy Business: Transcriptome Analysis Reveals the Involvement
of Thioredoxin A in Redox Homeostasis, Oxidative Stress, Sulfur Metabolism,
and Cellular Differentiation in Bacillus subtilis},
journal = {J. Bacteriol.},
year = {2005},
volume = {187},
pages = {3921--3930},
number = {12},
month = jun,
abstract = {Thioredoxins are important thiol-reactive proteins. Most knowledge
about this class of proteins is derived from proteome studies, and
little is known about the global transcriptional response of cells
to various thioredoxin levels. In Bacillus subtilis, thioredoxin
A is encoded by trxA and is essential for viability. In this study,
we report the effects of minimal induction of a strain carrying an
IPTG (isopropyl-{beta}-D-thiogalactopyranoside)-inducible trxA gene
(ItrxA) on transcription levels, as determined by DNA macroarrays.
The effective depletion of thioredoxin A leads to the induction of
genes involved in the oxidative stress response (but not those dependent
on PerR), phage-related functions, and sulfur utilization. Also,
several stationary-phase processes, such as sporulation and competence,
are affected. The majority of these phenotypes are rescued by a higher
induction level of ItrxA, leading to an approximately wild-type level
of thioredoxin A protein. A comparison with other studies shows that
the effects of thioredoxin depletion are distinct from, but show
some similarity to, oxidative stress and disulfide stress. Some of
the transcriptional effects may be linked to thioredoxin-interacting
proteins. Finally, thioredoxin-linked processes appear to be conserved
between prokaryotes and eukaryotes.},
url = {http://jb.asm.org/cgi/content/abstract/187/12/3921}
}
@ARTICLE{Smoot2002,
author = {Smoot, Laura M. and McCormick, John K. and Smoot, James C. and Hoe,
Nancy P. and Strickland, Ian and Cole, Robert L. and Barbian, Kent
D. and Earhart, Cathleen A. and Ohlendorf, Douglas H. and Veasy,
L. George and Hill, Harry R. and Leung, Donald Y. M. and Schlievert,
Patrick M. and Musser, James M.},
title = {Characterization of Two Novel Pyrogenic Toxin Superantigens Made
by an Acute Rheumatic Fever Clone of Streptococcus pyogenes Associated
with Multiple Disease Outbreaks},
journal = {Infect. Immun.},
year = {2002},
volume = {70},
pages = {7095--7104},
number = {12},
month = dec,
abstract = {The pathogenesis of acute rheumatic fever (ARF) is poorly understood.
We identified two contiguous bacteriophage genes, designated speL
and speM, encoding novel inferred superantigens in the genome sequence
of an ARF strain of serotype M18 group A streptococcus (GAS). speL
and speM were located at the same genomic site in 33 serotype M18
isolates, and no nucleotide sequence diversity was observed in the
33 strains analyzed. Furthermore, the genes were absent in 13 non-M18
strains tested. These data indicate a recent acquisition event by
a distinct clone of serotype M18 GAS. speL and speM were transcribed
in vitro and upregulated in the exponential phase of growth. Purified
SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes
and human peripheral blood mononuclear cells in picogram amounts.
SpeL preferentially expanded human T cells expressing T-cell receptors
V{beta}1, V{beta}5.1, and V{beta}23, and SpeM had specificity for
V{beta}1 and V{beta}23 subsets, indicating that both proteins had
superantigen activity. SpeL was lethal in two animal models of streptococcal
toxic shock, and SpeM was lethal in one model. Serologic studies
indicated that ARF patients were exposed to serotype M18 GAS, SpeL,
and SpeM. The data demonstrate that SpeL and SpeM are pyrogenic toxin
superantigens and suggest that they may participate in the host-pathogen
interactions in some ARF patients.},
url = {http://iai.asm.org/cgi/content/abstract/70/12/7095}
}
@ARTICLE{Smuc2009,
author = {Smuc, Tina and Rizner, Tea Lanisnik},
title = {Aberrant pre-receptor regulation of estrogen and progesterone action
in endometrial cancer},
journal = {Molecular and Cellular Endocrinology},
year = {2009},
volume = {301},
pages = {74--82},
number = {1-2},
month = mar,
abstract = {Endometrial cancer is related to estrogen stimulation not opposed
by progesterone. We have examined expression of the pre-receptor
regulatory enzymes aromatase, 17[beta]-hydroxysteroid dehydrogenases
(17[beta]-HSDs), 20[alpha]-hydroxysteroid dehydrogenases (20[alpha]-HSDs),
sulfatase and sulfotransferase, and estrogen (ERs) and progesterone
(PRs) receptors in samples of endometrial cancer and adjacent normal
endometrium. No significant gene up-regulation was seen, although
aromatase, AKR1C3, a 17[beta]-HSD and 20[alpha]-HSD, and AKR1C1,
the major 20[alpha]-HSD, were up-regulated in 50% of samples. Significant
down-regulation was seen for 17[beta]-HSD types 1 and 7, sulfotransferase,
ER[alpha], ER[beta], PR-AB. Western blotting revealed higher levels
of AKR1C3 and PR-B and lower levels of ER[alpha] in cancerous endometrium,
and immunohistochemistry confirmed expression of AKR1C3, PR-B and
ER[alpha] at the cellular level. Up-regulation of aromatase in concert
with AKR1C3 can lead to increased levels of estradiol, which acts
via ER[alpha]. Up-regulation of AKR1C1 and AKR1C3 can result in lower
levels of the protective progesterone, which acts mainly via PR-B.},
booktitle = {Pre-receptor steroid metabolism as target for pharmacological treatment},
issn = {0303-7207},
keywords = {Pre-receptor regulation, Hydroxysteroid dehydrogenases, Aromatase,
Sulfatase, Sulfotransferase, ER, PR},
url = {http://www.sciencedirect.com/science/article/B6T3G-4TJ6FN8-2/2/50c26d0b7f3943e8e36e8955139e8ce9}
}
@ARTICLE{Sneddon2006,
author = {Sneddon, Alan A. and McLeod, Ewan and Wahle, Klaus W.J. and Arthur,
John R.},
title = {Cytokine-induced monocyte adhesion to endothelial cells involves
platelet-activating factor: Suppression by conjugated linoleic acid},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology
of Lipids},
year = {2006},
volume = {1761},
pages = {793--801},
number = {7},
month = jul,
issn = {1388-1981},
keywords = {CLA, Inflammation, PUFA, Phospholipid, Cell adhesion, PAF antagonist},
url = {http://www.sciencedirect.com/science/article/B6VNN-4K3CM32-2/2/5c0dd2723071dcbf047eb8622ece5467}
}
@ARTICLE{Snell-Rood2011,
author = {Snell-Rood, Emilie C. and Cash, Amy and Han, Mira V. and Kijimoto,
Teiya and Andrews, Justen and Moczek, Armin P.},
title = {Developmental Decoupling Of Alternative Phenotypes: Insights From
The Transcriptomes Of Horn-polyphenic Beetles},
journal = {Evolution},
year = {2011},
volume = {65},
pages = {231--245},
number = {1},
abstract = {Developmental mechanisms play an important role in determining the
costs, limits, and evolutionary consequences of phenotypic plasticity.
One issue central to these claims is the hypothesis of developmental
decoupling, where alternate morphs result from evolutionarily independent
developmental pathways. We address this assumption through a microarray
study that tests whether differences in gene expression between alternate
morphs are as divergent as those between sexes, a classic example
of developmental decoupling. We then examine whether genes with morph-biased
expression are less conserved than genes with shared expression between
morphs, as predicted if developmental decoupling relaxes pleiotropic
constraints on divergence. We focus on the developing horns and brains
of two species of horned beetles with impressive sexual- and morph-dimorphism
in the expression of horns and fighting behavior. We find that patterns
of gene expression were as divergent between morphs as they were
between sexes. However, overall patterns of gene expression were
also highly correlated across morphs and sexes. Morph-biased genes
were more evolutionarily divergent, suggesting a role of relaxed
pleiotropic constraints or relaxed selection. Together these results
suggest that alternate morphs are to some extent developmentally
decoupled, and that this decoupling has significant evolutionary
consequences. However, alternative morphs may not be as developmentally
decoupled as sometimes assumed and such hypotheses of development
should be revisited and refined.},
doi = {10.1111/j.1558-5646.2010.01106.x},
issn = {1558-5646},
keywords = {Developmental decoupling, horned beetles, microarray, Onthophagus,
pleiotropy, polyphenism, relaxed selection, sexual dimorphism},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1558-5646.2010.01106.x}
}
@ARTICLE{Snelling2009,
author = {Snelling, S. and Rout, R. and Xia, Z. and Andrew, C.J. and Hulley,
P.A. and Price, A.J.},
title = {446 a microarray analysis of damaged versus undamaged cartilage in
anteromedial gonarthrosis},
journal = {Osteoarthritis and Cartilage},
year = {2009},
volume = {17},
pages = {S238--S238},
number = {Supplement 1},
month = sep,
booktitle = {ABSTRACTS OF THE 2009 WORLD CONGRESS ON OSTEOARTHRITIS},
issn = {1063-4584},
url = {http://www.sciencedirect.com/science/article/B6WP3-4X6FC1T-JN/2/1237baecd02f4ae79dcb8052035e6ff3}
}
@ARTICLE{Snider2009,
author = {Snider, Lauren and Asawachaicharn, Amy and Tyler, Ashlee E. and Geng,
Linda N. and Petek, Lisa M. and Maves, Lisa and Miller, Daniel G.
and Lemmers, Richard J.L.F. and Winokur, Sara T. and Tawil, Rabi
and van der Maarel, Silvere M. and Filippova, Galina N. and Tapscott,
Stephen J.},
title = {RNA transcripts, miRNA-sized fragments and proteins produced from
D4Z4 units: new candidates for the pathophysiology of facioscapulohumeral
dystrophy},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {2414--2430},
number = {13},
month = jul,
abstract = {Deletion of a subset of the D4Z4 macrosatellite repeats in the subtelomeric
region of chromosome 4q causes facioscapulohumeral muscular dystrophy
(FSHD) when occurring on a specific haplotype of 4qter (4qA161).
Several genes have been examined as candidates for causing FSHD,
including the DUX4 homeobox gene in the D4Z4 repeat, but none have
been definitively shown to cause the disease, nor has the full extent
of transcripts from the D4Z4 region been carefully characterized.
Using strand-specific RT-PCR, we have identified several sense and
antisense transcripts originating from the 4q D4Z4 units in wild-type
and FSHD muscle cells. Consistent with prior reports, we find that
the DUX4 transcript from the last (most telomeric) D4Z4 unit is polyadenylated
and has two introns in its 3-prime untranslated region. In addition,
we show that this transcript generates (i) small si/miRNA-sized fragments,
(ii) uncapped, polyadenylated 3-prime fragments that encode the conserved
C-terminal portion of DUX4 and (iii) capped and polyadenylated mRNAs
that contain the double-homeobox domain of DUX4 but splice-out the
C-terminal portion. Transfection studies demonstrate that translation
initiation at an internal methionine can produce the C-terminal polypeptide
and developmental studies show that this peptide inhibits myogenesis
at a step between MyoD transcription and the activation of MyoD target
genes. Together, we have identified new sense and anti-sense RNA
transcripts, novel mRNAs and mi/siRNA-sized RNA fragments generated
from the D4Z4 units that are new candidates for the pathophysiology
of FSHD.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/13/2414}
}
@ARTICLE{Snoek2009,
author = {Snoek, Robert and Cheng, Helen and Margiotti, Katia and Wafa, Latif
A. and Wong, Charmaine A. and Wong, Erica Chan and Fazli, Ladan and
Nelson, Colleen C. and Gleave, Martin E. and Rennie, Paul S.},
title = {In vivo Knockdown of the Androgen Receptor Results in Growth Inhibition
and Regression of Well-Established, Castration-Resistant Prostate
Tumors},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {39--47},
number = {1},
month = jan,
abstract = {Purpose: Progression to the castration-resistant state is the incurable
and lethal end stage of prostate cancer, and there is strong evidence
that androgen receptor (AR) still plays a central role in this process.
We hypothesize that knocking down AR will have a major effect on
inhibiting growth of castration-resistant tumors. Experimental Design:
Castration-resistant C4-2 human prostate cancer cells stably expressing
a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were
generated to directly test the effects of AR knockdown in C4-2 human
prostate cancer cells and tumors. Results: In vitro expression of
AR shRNA resulted in decreased levels of AR mRNA and protein, decreased
expression of prostate-specific antigen (PSA), reduced activation
of the PSA-luciferase reporter, and growth inhibition of C4-2 cells.
Gene microarray analyses revealed that AR knockdown under hormone-deprived
conditions resulted in activation of genes involved in apoptosis,
cell cycle regulation, protein synthesis, and tumorigenesis. To ensure
that tumors were truly castration-resistant in vivo, inducible AR
shRNA expressing C4-2 tumors were grown in castrated mice to an average
volume of 450 mm3. In all of the animals, serum PSA decreased, and
in 50% of them, there was complete tumor regression and disappearance
of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant
prostate tumors, knockdown of AR can decrease serum PSA, inhibit
tumor growth, and frequently cause tumor regression. This study is
the first direct evidence that knockdown of AR is a viable therapeutic
strategy for treatment of prostate tumors that have already progressed
to the castration-resistant state.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/1/39}
}
@ARTICLE{Snow2009,
author = {Snow, Ayelet B. and Khalyfa, Abdelnaby and Serpero, Laura D. and
Capdevila, Oscar Sans and Kim, Jinkwan and Buazza, Muhamad O. and
Gozal, David},
title = {Catecholamine alterations in pediatric obstructive sleep apnea: Effect
of obesity},
journal = {Pediatr. Pulmonol.},
year = {2009},
volume = {44},
pages = {559--567},
number = {6},
abstract = {Abstract 10.1002/ppul.21015.abs Study Objectives Obstructive sleep
apnea (OSA) elicits increased sympathetic activity in adults and
increased urinary catecholamines. Moreover, urinary catecholamine
excretion is altered in obese patients. We hypothesized that morning
urine catecholamine levels would be correlated with the severity
of obstructive sleep apnea and degree of obesity in children. Methods
Children referred to the pediatric sleep center for habitual snoring
underwent overnight polysomnography, and the first morning voided
urine sample was collected. Urinary concentrations of norepinephrine,
epinephrine and dopamine were measured and corrected for creatinine
levels. In a subset of children, blood samples were drawn and gene
expression of catecholamine-relevant genes analyzed by quantitative
real-time PCR. Results One hundred fifty-nine children were recruited
and completed the protocol. Children with OSA had significantly higher
urinary norepinephrine and epinephrine levels, but not dopamine,
compared to habitual snorers (norepinephrine: 40.1 ± 24.7 ng/mg
creatinine vs. 31.6 ± 16.2 ng/mg creatinine, P < 0.01; epinephrine:
6.4 ± 10.5 ng/mg vs. 4.5 ± 0.5 ng/mg, P < 0.01). There
was a positive correlation between norepinephrine and epinephrine
values and polysomnographic indices, but no effect of obesity on
catecholamine levels. In addition, expression of several of the major
genes involved in synthesis and transport of catecholamines, as well
as in selected receptors were compatible with increased bioavailability
of catecholamines. Conclusions In children with OSA, morning urinary
norepinephrine and epinephrine levels are significantly higher than
those without OSA, and correlate with the severity of the disease.
Gene expression patterns are in agreement with such findings. Urine
catecholamine levels do not appear to be influenced by the presence
of obesity. Thus, altered sympathetic activity in OSA patients appears
to occur independently of the presence of obesity. Pediatr Pulmonol.
2009; 44:559–567. © 2009 Wiley-Liss, Inc.},
issn = {1099-0496},
keywords = {autonomic nervous system, sympathetic, catecholamines, hypoxia, sleep
apnea},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ppul.21015}
}
@ARTICLE{Snowden2005,
author = {Snowden, Kimberley C. and Simkin, Andrew J. and Janssen, Bart J.
and Templeton, Kerry R. and Loucas, Holly M. and Simons, Joanne L.
and Karunairetnam, Sakuntala and Gleave, Andrew P. and Clark, David
G. and Klee, Harry J.},
title = {The Decreased apical dominance1/Petunia hybrida CAROTENOID CLEAVAGE
DIOXYGENASE8 Gene Affects Branch Production and Plays a Role in Leaf
Senescence, Root Growth, and Flower Development},
journal = {PLANT CELL},
year = {2005},
volume = {17},
pages = {746--759},
number = {3},
month = mar,
abstract = {Carotenoids and carotenoid cleavage products play an important and
integral role in plant development. The Decreased apical dominance1
(Dad1)/PhCCD8 gene of petunia (Petunia hybrida) encodes a hypothetical
carotenoid cleavage dioxygenase (CCD) and ortholog of the MORE AXILLARY
GROWTH4 (MAX4)/AtCCD8 gene. The dad1-1 mutant allele was inactivated
by insertion of an unusual transposon (Dad-one transposon), and the
dad1-3 allele is a revertant allele of dad1-1. Consistent with its
role in producing a graft-transmissible compound that can alter branching,
the Dad1/PhCCD8 gene is expressed in root and shoot tissue. This
expression is upregulated in the stems of the dad1-1, dad2, and dad3
increased branching mutants, indicating feedback regulation of the
gene in this tissue. However, this feedback regulation does not affect
the root expression of Dad1/PhCCD8. Overexpression of Dad1/PhCCD8
in the dad1-1 mutant complemented the mutant phenotype, and RNA interference
in the wild type resulted in an increased branching phenotype. Other
differences in phenotype associated with the loss of Dad1/PhCCD8
function included altered timing of axillary meristem development,
delayed leaf senescence, smaller flowers, reduced internode length,
and reduced root growth. These data indicate that the substrate(s)
and/or product(s) of the Dad1/PhCCD8 enzyme are mobile signal molecules
with diverse roles in plant development.},
url = {http://www.plantcell.org/cgi/content/abstract/17/3/746}
}
@ARTICLE{Snyder2010,
author = {Snyder, Elizabeth M. and Small, Christopher L. and Bomgardner, Daniela
and Xu, Bingfang and Evanoff, Ryan and Griswold, Michael D. and Hinton,
Barry T.},
title = {Gene expression in the efferent ducts, epididymis, and vas deferens
during embryonic development of the mouse},
journal = {Dev. Dyn.},
year = {2010},
volume = {239},
pages = {2479--2491},
number = {9},
abstract = {Abstract 10.1002/dvdy.22378.abs The tissues of the male reproductive
tract are characterized by distinct morphologies, from highly coiled
to un-coiled. Global gene expression profiles of efferent ducts,
epididymis, and vas deferens were generated from embryonic day 14.5
to postnatal day 1 as tissue-specific morphologies emerge. Expression
of homeobox genes, potential mediators of tissue-specific morphological
development, was assessed. Twenty homeobox genes were identified
as either tissue-enriched, developmentally regulated, or both. Additionally,
ontology analysis demonstrated cell adhesion to be highly regulated
along the length of the reproductive tract. Regulators of cell adhesion
with variable expression between the three tissues were identified
including Alcam, various cadherins, and multiple integrins. Immunofluorescence
localization of the cell adhesion regulators POSTN and CDH2 demonstrated
cell adhesion in the epithelium and mesenchyme of the epididymis
may change throughout development. These results suggest cell adhesion
may be modulated in a tissue-specific manner, playing an important
role in establishing each tissue's final morphology. Developmental
Dynamics 239:2479–2491, 2010. © 2010 Wiley-Liss, Inc.},
issn = {1097-0177},
keywords = {microarray, epididymis, vas deferens, efferent duct, male reproductive
tract},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.22378}
}
@ARTICLE{Snyder2009,
author = {Snyder, Elizabeth M. and Small, Christopher L. and Li, Ying and Griswold,
Michael D.},
title = {Regulation of Gene Expression by Estrogen and Testosterone in the
Proximal Mouse Reproductive Tract},
journal = {Biol Reprod},
year = {2009},
volume = {81},
pages = {707--716},
number = {4},
month = oct,
abstract = {The role of estrogen and testosterone in the regulation of gene expression
in the proximal reproductive tract is not completely understood.
To address this question, mice were treated with testosterone or
estradiol, and RNA from the efferent ducts and caput epididymides
was processed and hybridized to Affymetrix M430 2.0 microarrays.
Analysis of array output identified probe sets in each tissue with
altered levels in hormone-treated versus control animals. Hormone
treatment efficacy was confirmed by determination of serum hormone
levels before and after treatment and by observed changes in transcript
levels of previously reported hormone-responsive genes. Tissue-specific
hormone sensitivity was observed with 2867 and 3197 probe sets changing
significantly in the efferent ducts after estrogen and testosterone
treatment, respectively. In the caput epididymidis, 117 and 268 probe
sets changed after estrogen and testosterone treatment, respectively,
demonstrating a greater response to hormone in the efferent ducts
than in the caput epididymidis. Transcripts sharing similar profiles
in the intact and hormone-treated animals compared with castrated
controls were also identified. Ontology analysis of probe sets revealed
that a significant number of hormone-regulated transcripts encode
proteins associated with lipid metabolism, transcription, and steroid
metabolism in both tissues. Real-time RT-PCR was used to confirm
array data and to investigate other potential hormone-responsive
regulators of proximal reproductive tract function. The results of
this work reveal previously unknown responses to estrogen in the
caput epididymidis and to testosterone in the efferent ducts, as
well as tissue-specific hormone sensitivity in the proximal reproductive
tract.},
url = {http://www.biolreprod.org/cgi/content/abstract/81/4/707}
}
@ARTICLE{Snyder2009a,
author = {Snyder, Joshua C. and Zemke, Anna C. and Stripp, Barry R.},
title = {Reparative Capacity of Airway Epithelium Impacts Deposition and Remodeling
of Extracellular Matrix},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2009},
volume = {40},
pages = {633--642},
number = {6},
month = jun,
abstract = {Defective epithelial repair in the setting of chronic lung disease
has been suggested to contribute to uncontrolled extracellular matrix
(ECM) deposition and development of fibrosis. We sought to directly
test this hypothesis through gene expression profiling of total lung
RNA isolated from mouse models of selective epithelial cell injury
that are associated with either productive or abortive repair. Analysis
of gene expression in repairing lungs of naphthalene-exposed mice
revealed prominent clusters of up-regulated genes with putative roles
in regulation of the extracellular matrix and cellular proliferation.
Further analysis of tenascin C (Tnc), a representative matrix protein,
in total lung RNA revealed a transient 4.5-fold increase in mRNA
abundance 1 day after injury and a return to steady-state levels
by Recovery Day 3. Tnc was deposited by the peribronchiolar mesenchyme
immediately after injury and was remodeled to basement membrane subtending
the bronchiolar epithelium during epithelial repair. Epithelial restitution
was accompanied by a decrease in Tnc mRNA and protein expression
to steady-state levels. In contrast, abortive repair using a transgenic
model allowing ablation of all reparative cells led to a progressive
increase in Tnc mRNA within lung tissue and accumulation of its gene
product within the subepithelial mesenchyme of both conducting airways
and alveoli. These data demonstrate that the ECM is dynamically remodeled
in response to selective epithelial cell injury and that this process
is activated without resolution in the setting of defective airway
epithelial repair.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/40/6/633}
}
@ARTICLE{Snyder2008,
author = {Snyder, Stacey and Thrall, Donald and Dewhirst, Mark and Owzar, Kouros
and Hauck, Marlene},
title = {Gene expression changes in canine sarcomas treated with radiation
and hyperthermia},
journal = {AACR Meeting Abstracts},
year = {2008},
volume = {2008},
pages = {1753--},
number = {1_Annual_Meeting},
month = apr,
url = {http://www.aacrmeetingabstracts.org}
}
@ARTICLE{Sobata2011,
author = {Sobata, Rieko and Matsumoto, Chieko and Igarashi, Masashi and Uchida,
Shigeharu and Momose, Shunya and Hino, Satoru and Satake, Masahiro
and Tadokoro, Kenji},
title = {No viremia of pandemic (H1N1) 2009 was demonstrated in blood donors
who had donated blood during the probable incubation period},
journal = {Transfusion},
year = {2011},
volume = {51},
pages = {1949--1956},
number = {9},
abstract = {BACKGROUND: In the spring of 2009, the novel swine-origin influenza
A (pandemic [H1N1] 2009) virus emerged and spread globally. Although
no established cases of transfusion-transmitted influenza have been
reported, the widespread outbreak of pandemic (H1N1) 2009 caused
serious concern regarding the safety of blood products. The Japanese
Red Cross Blood Centers have intercepted blood products with accompanying
postdonation information indicating possible pandemic (H1N1) 2009
infection. To study the risk of transmission of pandemic (H1N1) 2009
by blood transfusion, we searched for the viral genome in such products
using nucleic acid amplification technology.STUDY DESIGN AND METHODS:
Between June and December 2009, blood components were collected from
579 blood donors who were diagnosed as or strongly suspected of having
pandemic (H1N1) 2009 within 7 days after donation. Viral RNA was
extracted from plasma and red blood cell (RBC) products, and RNA
samples were subjected to real-time reverse transcription–polymerase
chain reaction of the hemagglutinin and matrix genes of the pandemic
(H1N1) 2009 virus.RESULTS: A total of 565 plasma and 413 RBC products
from the 579 blood donors were available. No viral RNA of the pandemic
(H1N1) 2009 was detected in any of the blood samples from the 579
blood donors.CONCLUSION: No viremia of pandemic (H1N1) 2009 was demonstrated
in any of the 579 blood donors who had most likely donated blood
during the incubation period. It is considered that the risk of transmitting
pandemic (H1N1) 2009 by blood transfusion is extremely low.},
doi = {10.1111/j.1537-2995.2011.03109.x},
issn = {1537-2995},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1537-2995.2011.03109.x}
}
@ARTICLE{Sobesky2007,
author = {Sobesky, Rodolphe and Feray, Cyrille and Rimlinger, François and
Derian, Nicolas and Dos Santos, Alexandre and Roque-Afonso, Anne-Marie
and Samuel, Didier and Bréchot, Christian and Thiers, Valérie},
title = {Distinct hepatitis C virus core and F protein quasispecies in tumoral
and nontumoral hepatocytes isolated via microdissection},
journal = {Hepatology},
year = {2007},
volume = {46},
pages = {1704--1712},
number = {6},
abstract = {Abstract 10.1002/hep.21898.abs Hepatitis C virus (HCV) genetic variability
may be involved in liver carcinogenesis. We investigated HCV core
and corresponding putative F protein genetic variability in hepatocellular
carcinoma (HCC) and cirrhotic nodules. Hepatocyte clusters from 7
patients with HCC and HCV1b-related cirrhosis were isolated via microdissection
of HCC tissues and 2 nontumoral cirrhotic nodules. The HCV core complementary
DNA was cloned and sequenced from each liver compartment and from
the serum of 2 patients. Nucleotide diversity and synonymous and
nonsynonymous substitutions were analyzed within and between compartments
via phylogenetic analysis and Mantel's test. Liver HCV RNA accumulation
was lower in HCC. Increased quasispecies diversity and complexity
was observed with HCC in 6 of 7 patients. Mantel's test demonstrated
marked compartmentalization of quasispecies between HCC and cirrhotic
nodules in all 7 patients and also between the 2 nontumoral nodules
in 5 of them. Synonymous–nonsynonymous substitution analysis indicated
low selection against tumoral core quasispecies in all patients and
a more selective pressure against F protein quasispecies in all compartments.
In the 2 subjects analyzed, HCC and nontumoral hepatocyte quasispecies
were only minor or undetected in serum. Conclusion: In tumoral hepatocytes,
low-replicating hepatitis C quasispecies are compartmentalized and
more diversified and are subjected to low selective pressure. Our
study supports the importance of core genetic variability in hepatocellular
carcinogenesis. (HEPATOLOGY 2007.) This is a corrected version of
the abstract first published online on 12 October 2007 — the corrected
version appears in print.},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.21898}
}
@ARTICLE{Sobreira2011,
author = {Sobreira, Nara L.M. and Gnanakkan, Veena and Walsh, Michael and Marosy,
Beth and Wohler, Elizabeth and Thomas, George and Hoover-Fong, Julie
E. and Hamosh, Ada and Wheelan, Sarah J. and Valle, David},
title = {Characterization of complex chromosomal rearrangements by targeted
capture and next-generation sequencing},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1720-1727},
number = {10},
abstract = {Translocations are a common class of chromosomal aberrations and can
cause disease by physically disrupting genes or altering their regulatory
environment. Some translocations, apparently balanced at the microscopic
level, include deletions, duplications, insertions, or inversions
at the molecular level. Traditionally, chromosomal rearrangements
have been investigated with a conventional banded karyotype followed
by arduous positional cloning projects. More recently, molecular
cytogenetic approaches using fluorescence in situ hybridization (FISH),
array comparative genomic hybridization (aCGH), or whole-genome SNP
genotyping together with molecular methods such as inverse PCR and
quantitative PCR have allowed more precise evaluation of the breakpoints.
These methods suffer, however, from being experimentally intensive
and time-consuming and of less than single base pair resolution.
Here we describe targeted breakpoint capture followed by next-generation
sequencing (TBCS) as a new approach to the general problem of determining
the precise structural characterization of translocation breakpoints
and related chromosomal aberrations. We tested this approach in three
patients with complex chromosomal translocations: The first had craniofacial
abnormalities and an apparently balanced t(2;3)(p15;q12) translocation;
the second has cleidocranial dysplasia (OMIM 119600 ) associated
with a t(2;6)(q22;p12.3) translocation and a breakpoint in RUNX2
on chromosome 6p; and the third has acampomelic campomelic dysplasia
(OMIM 114290 ) associated with a t(5;17)(q23.2;q24) translocation,
with a breakpoint upstream of SOX9 on chromosome 17q. Preliminary
studies indicated complex rearrangements in patients 1 and 3 with
a total of 10 predicted breakpoints in the three patients. By using
TBCS, we quickly and precisely defined eight of the 10 breakpoints.},
doi = {10.1101/gr.122986.111},
eprint = {http://genome.cshlp.org/cgi/reprint/21/10/1720.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/10/1720}
}
@ARTICLE{Soccio2011,
author = {Soccio, Raymond E. and Tuteja, Geetu and Everett, Logan J. and Li,
Zhaoyu and Lazar, Mitchell A. and Kaestner, Klaus H.},
title = {Species-Specific Strategies Underlying Conserved Functions of Metabolic
Transcription Factors},
journal = {Mol. Endocrinol.},
year = {2011},
volume = {25},
pages = {694--706},
number = {4},
month = apr,
abstract = {The winged helix protein FOXA2 and the nuclear receptor peroxisome
proliferator-activated receptor-{gamma} (PPAR{gamma}) are highly
conserved, regionally expressed transcription factors (TFs) that
regulate networks of genes controlling complex metabolic functions.
Cistrome analysis for Foxa2 in mouse liver and PPAR{gamma} in mouse
adipocytes has previously produced consensus-binding sites that are
nearly identical to those used by the corresponding TFs in human
cells. We report here that, despite the conservation of the canonical
binding motif, the great majority of binding regions for FOXA2 in
human liver and for PPAR{gamma} in human adipocytes are not in the
orthologous locations corresponding to the mouse genome, and vice
versa. Of note, TF binding can be absent in one species despite sequence
conservation, including motifs that do support binding in the other
species, demonstrating a major limitation of in silico binding site
prediction. Whereas only approximately 10% of binding sites are conserved,
gene-centric analysis reveals that about 50% of genes with nearby
TF occupancy are shared across species for both hepatic FOXA2 and
adipocyte PPAR{gamma}. Remarkably, for both TFs, many of the shared
genes function in tissue-specific metabolic pathways, whereas species-unique
genes fail to show enrichment for these pathways. Nonetheless, the
species-unique genes, like the shared genes, showed the expected
transcriptional regulation by the TFs in loss-of-function experiments.
Thus, species-specific strategies underlie the biological functions
of metabolic TFs that are highly conserved across mammalian species.
Analysis of factor binding in multiple species may be necessary to
distinguish apparent species-unique noise and reveal functionally
relevant information.},
comment = {10.1210/me.2010-0454},
url = {http://mend.endojournals.org/cgi/content/abstract/25/4/694}
}
@ARTICLE{Sodhi2011,
author = {Monsheel S. Sodhi and Micah Simmons and Robert McCullumsmith and
Vahram Haroutunian and James H. Meador-Woodruff},
title = {Glutamatergic Gene Expression Is Specifically Reduced in Thalamocortical
Projecting Relay Neurons in Schizophrenia},
journal = {Biological Psychiatry},
year = {2011},
volume = {70},
pages = {646 - 654},
number = {7},
note = {Genes, Brain Development, and Schizophrenia},
abstract = {Background Impairment of glutamate neurons that relay sensory and
cognitive information from the medial dorsal thalamus to the dorsolateral
prefrontal cortex and other cortical regions may contribute to the
pathophysiology of schizophrenia. In this study, we have assessed
the cell-specific expression of glutamatergic transcripts in the
medial dorsal thalamus. Methods We used laser capture microdissection
to harvest two populations of medial dorsal thalamic cells, one enriched
with glutamatergic relay neurons and the other with gamma-aminobutyric
acidergic neurons and astroglia, from postmortem brains of subjects
with schizophrenia (n = 14) and a comparison group (n = 20). Quantitative
polymerase chain reaction of extracted RNA was used to assay gene
expression in the different cell populations. Results The transcripts
encoding the ionotropic glutamate receptor subunits NR2D, GluR3,
GluR6, GluR7, and the intracellular proteins GRIP1 and SynGAP1 were
significantly decreased in relay neurons but not in the mixed glial
and interneuron population in schizophrenia. Conclusions Our data
suggest that reduced ionotropic glutamatergic expression occurs selectively
in neurons, which give rise to the cortical projections of the medial
dorsal thalamus in schizophrenia, rather than in thalamic cells that
function locally. Our findings indicate that glutamatergic innervation
is dysfunctional in the circuitry between the medial dorsal thalamus
and cortex.},
doi = {10.1016/j.biopsych.2011.02.022},
issn = {0006-3223},
keywords = {Laser capture microdissection},
url = {http://www.sciencedirect.com/science/article/pii/S0006322311001971}
}
@ARTICLE{Sodowich2007,
author = {Sodowich, BI and Fadl, I and Burns, C},
title = {Method validation of in vitro RNA transcript analysis on the Agilent
2100 Bioanalyzer.},
journal = {Electrophoresis},
year = {2007},
volume = {28},
pages = {2368-78--},
number = {14},
month = jul,
abstract = {The Agilent 2100 Bioanalyzer can characterize in vitro RNA transcripts
for their integrity, purity, concentration, and size. The results
are comparable to denatured agarose electrophoresis with ethidium
bromide staining and UV spectrophotometry combined. In this report,
we describe our strategy for validating this method following the
International Conference on Harmonization guidelines. The assay has
a linear range of quantitation between 500 and 25 ng/microL. Quantitation
accuracy is within +/-20% of measurements produced from spectrophotometry
and sizing accuracy is within +/-7% based on theoretical sizes. Concentration
and sizing measurements within a single assay produce RSDs that are
<10 and <2%, respectively, indicating good precision. The method
also maintains a tolerable precision when altering operator, day,
and reagent kit lot. The RSD for quantitation is Functional Mouse Genomics},
abstract = {Transcription factors (TFs) play a central role in the development
of multicellular organisms. The sequential actions of critical TFs
direct cells to adopt defined differentiation pathways leading to
functional, fully differentiated tissues. Here, we describe a generic
experimental pipeline that integrates biochemistry, genetics and
next generation sequencing with bioinformatics to characterize TF
complexes composition, function and target genes at a genome-wide
scale. We show an application of this experimental pipeline which
aims to unravel the molecular events taking place during hematopoietic
cell differentiation.},
doi = {10.1016/j.ymeth.2010.08.002},
issn = {1046-2023},
keywords = {Transcription factor},
url = {http://www.sciencedirect.com/science/article/pii/S1046202310002033}
}
@ARTICLE{Soler2007,
author = {Soler, Marcal and Serra, Olga and Molinas, Marisa and Huguet, Gemma
and Fluch, Silvia and Figueras, Merce},
title = {A Genomic Approach to Suberin Biosynthesis and Cork Differentiation},
journal = {Plant Physiology},
year = {2007},
volume = {144},
pages = {419--431},
number = {1},
month = may,
abstract = {Cork (phellem) is a multilayered dead tissue protecting plant mature
stems and roots and plant healing tissues from water loss and injuries.
Cork cells are made impervious by the deposition of suberin onto
cell walls. Although suberin deposition and cork formation are essential
for survival of land plants, molecular studies have rarely been conducted
on this tissue. Here, we address this question by combining suppression
subtractive hybridization together with cDNA microarrays, using as
a model the external bark of the cork tree (Quercus suber), from
which bottle cork is obtained. A suppression subtractive hybridization
library from cork tree bark was prepared containing 236 independent
sequences; 69% showed significant homology to database sequences
and they corresponded to 135 unique genes. Out of these genes, 43.5%
were classified as the main pathways needed for cork biosynthesis.
Furthermore, 19% could be related to regulatory functions. To identify
genes more specifically required for suberin biosynthesis, cork expressed
sequence tags were printed on a microarray and subsequently used
to compare cork (phellem) to a non-suberin-producing tissue such
as wood (xylem). Based on the results, a list of candidate genes
relevant for cork was obtained. This list includes genes for the
synthesis, transport, and polymerization of suberin monomers such
as components of the fatty acid elongase complexes, ATP-binding cassette
transporters, and acyltransferases, among others. Moreover, a number
of regulatory genes induced in cork have been identified, including
MYB, No-Apical-Meristem, and WRKY transcription factors with putative
functions in meristem identity and cork differentiation.},
url = {http://www.plantphysiol.org/cgi/content/abstract/144/1/419}
}
@ARTICLE{Solheim2007,
author = {Solheim, Margrete and Aakra, Agot and Vebo, Heidi and Snipen, Lars
and Nes, Ingolf F.},
title = {Transcriptional Responses of Enterococcus faecalis V583 to Bovine
Bile and Sodium Dodecyl Sulfate},
journal = {Appl. Envir. Microbiol.},
year = {2007},
volume = {73},
pages = {5767--5774},
number = {18},
month = sep,
abstract = {Resistance to bile is a prerequisite property of the gastrointestinal
bacterial flora. Bile acids are powerful detergents, and resistance
to sodium dodecyl sulfate (SDS) has therefore often been considered
relevant to studies of bile resistance. We have studied the effects
of bovine bile (BB) and SDS on Enterococcus faecalis V583 by traditional
growth studies and microarrays. Transcriptional responses were studied
by time course experiments. In the presence of BB (V583-BB) or SDS
(V583-SDS), 308 and 209 genes were identified as differentially expressed
at one or more time points, respectively. In V583 treated with both
BB and SDS (V583-BB-SDS), 254 genes showed differential expression.
Detergents exert their toxic effects primarily on the microbial membrane.
The enrichment of differentially transcribed genes that encode proteins
with membrane-associated functions and/or locations indicates a major
impact of all three treatments on the integrity and functionality
of the cell membrane. Two gene clusters involved in fatty acid biosynthesis
were repressed in V583-BB and V583-BB-SDS and partly induced in V583-SDS.
Furthermore, two EmrB/QacA family drug resistance transporters and
a vacuolar-type ATPase were induced in V583-BB and V583-BB-SDS. None
of the putative bile salt hydrolase homologs in V583 showed differential
expression during the bile treatments. The transcriptional profile
of V583-BB-SDS was qualitatively more similar to the response in
V583-BB than to that in V583-SDS, suggesting that the presence of
bile suppresses the effects of SDS in V583-BB-SDS. The overall results
presented here indicate that different mechanisms are involved in
detergent resistance in E. faecalis.},
url = {http://aem.asm.org/cgi/content/abstract/73/18/5767}
}
@ARTICLE{Solis2007,
author = {Solis, Mayra and Romieu-Mourez, Raphaëlle and Goubau, Delphine and
Grandvaux, Nathalie and Mesplede, Thibault and Julkunen, Ilkka and
Nardin, Alessandra and Salcedo, Margarita and Hiscott, John},
title = {Involvement of TBK1 and IKKϵ in lipopolysaccharide-induced activation
of the interferon response in primary human macrophages},
journal = {Eur. J. Immunol.},
year = {2007},
volume = {37},
pages = {528--539},
number = {2},
abstract = {Abstract 10.1002/eji.200636090.abs Interferon (IFN) is an important
effector of the innate immune response, induced by different viral
or bacterial components through Toll-like receptor-dependent and
-independent mechanisms. In human macrophages and macrophage-activated
killer cells, we demonstrate that (i) the type I IFN response to
lipopolysaccharide (LPS) is weak compared to the host response to
virus infection; (ii) there is a temporal difference in the induction
of tank-binding kinase-1 (TBK1) and IkappaB kinase (IKK)-related
kinase epsilon (IKKϵ) kinase activities in response to LPS, with
TBK1 activated early and IKKϵ induced in the late phase of IFN induction;
and (iii) interferon regulatory factor (IRF)-7 is induced following
LPS treatment, but there is no evidence that IRF-7 becomes activated
by phosphorylation in vivo. Specifically, TBK1 kinase activity is
rapidly increased after LPS stimulation (15 min) whereas IKKϵ
activation occurs at 8 h. RNA interference-mediated inhibition
of TBK1 and IKKϵ expression in macrophages interfere with IFNB and
IRF7 gene expression following LPS activation. Macrophage priming
with rIFN-α increased IRF-7 expression, led to a sharp up-regulation
of the IFNB gene and to a rapid induction of IFNA2 upon LPS stimulation.
These data support a differential role of TBK1 and IKKϵ in the downstream
response mediated by IRF-3 and IRF-7 to LPS in primary human macrophages.},
issn = {1521-4141},
keywords = {Lipopolysaccharide, Interferon regulatory factors, Tank-binding kinase-1,
IkappaB kinase (IKK)-related kinase epsilon, Type I interferon},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200636090}
}
@ARTICLE{Sollero2011,
author = {Sollero, B. P. and Guimarães, S. E. F. and Rilington, V. D. and
Tempelman, R. J. and Raney, N. E. and Steibel, J. P. and Guimarães,
J. D. and Lopes, P. S. and Lopes, M. S. and Ernst, C. W.},
title = {Transcriptional profiling during foetal skeletal muscle development
of Piau and Yorkshire–Landrace cross-bred pigs},
journal = {Animal Genetics},
year = {2011},
volume = {42},
pages = {600--612},
number = {6},
abstract = {Skeletal muscle development is a complex process involving the coordinated
expression of thousands of genes. The aim of this study was to identify
differentially expressed genes in longissimus dorsi (LD) muscle of
pigs at 40 and 70Â days (d) of gestation (developmental stages encompassing
primary and secondary fibre formation) in Yorkshire–Landrace (YL)
cross-bred pigs and Piau pigs (a naturalized Brazilian breed), which
are two breed types that differ in muscularity. Foetuses were obtained
from gilts at each gestational age (n = 3 YL; n = 4 Piau), and
transcriptional profiling was performed using the Pigoligoarray microarray
containing 20Â 400 oligonucleotides. A total of 486 oligonucleotides
were differentially expressed (fold change (FC) ≥ 1.5; false
discovery rate (FDR) ≤ 0.05) between 40 and 70 d gestation in
either YL or Piau pigs, and a total of 1300 oligonucleotides were
differentially expressed (FC ≥ 1.5; FDR ≤ 0.05) between YL
and Piau pigs at either age. Gene ontology annotation and pathway
analyses determined functional classifications for differentially
expressed genes and revealed breed type–specific developmental
expression patterns. Thirteen genes were selected for confirmation
by qRT-PCR analyses, and expression patterns for most of these genes
were confirmed, providing further insight into the roles of these
genes in pig muscle development. This study revealed both developmental
and breed type–specific patterns of gene expression in foetal pig
skeletal muscle, including genes not previously associated with myogenesis.
This information will contribute to future pig genetic improvement
efforts.},
doi = {10.1111/j.1365-2052.2011.02186.x},
issn = {1365-2052},
keywords = {foetal skeletal muscle, pig, transcriptional profiling},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2011.02186.x}
}
@ARTICLE{Sollid2005,
author = {Sollid, Jorund and Kjernsli, Aina and De Angelis, Paula M. and Rohr,
Asmund K. and Nilsson, Goran E.},
title = {Cell proliferation and gill morphology in anoxic crucian carp},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2005},
volume = {289},
pages = {R1196--1201},
number = {4},
month = oct,
abstract = {Is DNA replication/cell proliferation in vertebrates possible during
anoxia? The oxygen dependence of ribonucleotide reductase (RNR) could
lead to a stop in DNA synthesis, thereby making anoxic DNA replication
impossible. We have studied this question in an anoxia-tolerant vertebrate,
the crucian carp (Carassius carassius), by examining 5'-bromo-2'-deoxyuridine
incorporation and proliferating cell nuclear antigen levels in the
gills, intestinal crypts, and liver. We exposed crucian carp to 1
and 7 days of anoxia followed by 7 days of reoxygenation. There was
a reduced incidence of S-phase cells (from 12.2 to 5.0%) in gills
during anoxia, which coincided with a concomitant increase of G0
cells. Anoxia also decreased the number of S-phase cells in intestine
(from 8.1 to 1.8%). No change in the fraction of S-phase cells ([~]1%)
in liver was found. Thus new S-phase cells after 7 days of anoxia
were present in all tissues, revealing a considerable rate of DNA
synthesis. Subsequently, the oxygen-dependent subunit of crucian
carp RNR (RNRR2) was cloned. We found no differences in amino acids
involved in radical generation and availability of the iron center
compared with mouse, which could have explained reduced oxygen dependence.
Furthermore, the amount of RNRR2 mRNA in gills did not decrease throughout
anoxia exposure. These results indicate that crucian carp is able
to sustain some cell proliferation in anoxia, possibly because RNRR2
retains its tyrosyl radical in anoxia, and that the replication machinery
is still maintained. Although hypoxia triggers a 7.5-fold increase
of respiratory surface area in crucian carp, this response was not
triggered in anoxia.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/289/4/R1196}
}
@ARTICLE{Solmone2009,
author = {Solmone, Mariacarmela and Vincenti, Donatella and Prosperi, Mattia
Carlo Felice and Bruselles, Alessandro and Ippolito, Giuseppe and
Capobianchi, Maria Rosaria},
title = {Use of Massively Parallel Ultradeep Pyrosequencing To Characterize
the Genetic Diversity of Hepatitis B Virus in Drug-Resistant and
Drug-Naive Patients and To Detect Minor Variants in Reverse Transcriptase
and Hepatitis B S Antigen},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {1718--1726},
number = {4},
month = feb,
abstract = {Direct population sequencing and reverse hybridization (line probe
assay [LiPA])-based methods are the most common methods for detecting
hepatitis B virus (HBV) drug resistance mutations, although only
mutations present in viral quasispecies with a prevalence of [≥]20%
can be detected by sequencing, and only known mutations are detected
by LiPA. Massively parallel ultradeep pyrosequencing (UDPS; GS FLX
platform) was used to analyze HBV quasispecies in reverse transcriptase
(RT) and hepatitis B S antigen (HBsAg) from five drug-naive patients
and eight drug-resistant patients. Eight primer pairs were used to
obtain partially overlapping amplicons, covering the RT gene from
codons 1 to 288 and the complete overlapping HBsAg sequence. A 1%
mutation frequency was selected as the cutoff based on an error rate
estimated on plasmid DNA. This technology enabled simultaneous analysis
of between 2,852 and 18,016 clonally amplified fragments from each
patient. The results indicate that UDPS has a relative sensitivity
much higher than both direct sequencing and LiPA. In addition, the
UDPS results are quantitative, allowing establishment of the relative
frequency of both known mutations and novel substitutions. Some of
the detected RT substitutions led to changes also in HBsAg. On the
whole, genotype D presented a higher heterogeneity than genotype
A. Considering the high quantity of information that can be provided
by a single test from one patient, the short turnaround time, the
information on substitution frequency, and the detection of rare
variants, there are strong advantages conferred by UDPS, and the
new method could play a relevant role in the clinical management
of HBV infection and therapy.},
url = {http://jvi.asm.org/cgi/content/abstract/83/4/1718}
}
@ARTICLE{Soloff2011,
author = {Soloff, Melvyn S. and Jeng, Yow-Jiun and Izban, Michael G. and Sinha,
Mala and Luxon, Bruce A. and Stamnes, Susan J. and England, Sarah
K.},
title = {Effects of Progesterone Treatment on Expression of Genes Involved
in Uterine Quiescence},
journal = {Reproductive Sciences},
year = {2011},
volume = {18},
pages = {781-797},
number = {8},
abstract = {An important action of progesterone during pregnancy is to maintain
the uterus in a quiescent state and thereby prevent preterm labor.
The causes of preterm labor are not well understood, so progesterone
action on the myometrium can provide clues about the processes that
keep the uterus from contracting prematurely. Accordingly, we have
carried out Affymetrix GeneChip analysis of progesterone effects
on gene expression in immortalized human myometrial cells cultured
from a patient near the end of pregnancy. Progesterone appears to
inhibit uterine excitability by a number of mechanisms, including
increased expression of calcium and voltage-operated K+ channels,
which dampens the electrical activity of the myometrial cell, downregulation
of agents, and receptors involved in myometrial contraction, reduction
in cell signal components that lead to increased intracellular Ca2+
concentrations in response to contractile stimuli, and downregulation
of proteins involved in the cross-linking of actin and myosin filaments
to produce uterine contractions.},
doi = {10.1177/1933719111398150},
eprint = {http://rsx.sagepub.com/cgi/reprint/18/8/781.pdf},
url = {http://rsx.sagepub.com/cgi/content/abstract/18/8/781}
}
@ARTICLE{Solomon2011,
author = {Solomon, K. and Murray, S. and Scott, L. and McDermott, S. and Drudy,
D. and Martin, A. and O'Donoghue, C. and Skally, M. and Burns, K.
and Fenelon, L. and Fitzpatrick, F. and Kyne, L. and Fanning, S.},
title = {An investigation of the subtype diversity of clinical isolates of
Irish Clostridium difficile ribotypes 027 and 078 by repetitive-extragenic
palindromic PCR},
journal = {J. Med. Microbiol.},
year = {2011},
volume = {60},
pages = {1080-1087},
number = {8},
abstract = {A repetitive-extragenic palindromic PCR (rep-PCR) subtyping method
(DiversiLab) in conjunction with ribotyping, toxinotyping and antimicrobial-susceptibility
testing was used to detect subtypes within Clostridium difficile
ribotypes 027 and 078. Clinical isolates of ribotypes 027 (toxinotype
III) (n = 30) and 078 (toxinotype V) (n = 23) were provided by health-care
facilities across the Republic of Ireland over 2 months in 2006 and
1 month in 2009. Ribotype 027 isolates were significantly more related
to each other (9 different subtype profiles) when compared to ribotype
078 isolates (14 different profiles) (P = 0.001; cut-off >90 % similarity).
Almost half of ribotype 078 isolates (45.5 %) showed no relationship
to each other. The clonality of ribotype 027 isolates suggests effective
adaptation to the human niche, whereas the considerable genetic diversity
within ribotype 078 isolates suggests that they may have originated
from a variety of sources. Subtyping correlated well with antimicrobial
susceptibility, in particular clindamycin susceptibility for ribotype
027, but diverse antimicrobial-susceptibility profiles were seen
in ribotype 078 isolates, even within a single health-care facility.
Between 2006 and 2009, a change in the predominant subtype of ribotype
027 was seen, with the recent clone representing half of all ribotype
027 isolates studied. This strain exhibited 89 % similarity to a
rep-PCR profile of the North American NAP-1 strain.},
doi = {10.1099/jmm.0.029983-0},
eprint = {http://jmm.sgmjournals.org/cgi/reprint/60/8/1080.pdf},
url = {http://jmm.sgmjournals.org/cgi/content/abstract/60/8/1080}
}
@ARTICLE{Solomon2008,
author = {Solomon, Katie and Robins, Adrian and Mahida, Yashwant R.},
title = {M1177 Cell Surface Binding and Internalisation of Clostridium difficile
Toxin a By Human Intestinal Epithelial Cells},
journal = {Gastroenterology},
year = {2008},
volume = {134},
pages = {A--354-A-355},
number = {4, Supplement 1},
month = apr,
booktitle = {2008 DDW Abstract Supplement},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4T3XF3T-230/2/25f5f27e75f204edb4faa70c18c5c6ee}
}
@BOOK{Soloviev2005,
title = {Chip Based Proteomics Technology},
publisher = {John Wiley \& Sons, Ltd},
year = {2005},
author = {Soloviev, Mikhail and Barry, Richard and Terrett, Jon},
pages = {217--249},
abstract = {Summary 10.1002/0470020202.ch11.abs This chapter contains sections
titled:},
booktitle = {Molecular Analysis and Genome Discovery},
issn = {9780470020203},
keywords = {proteomics, gel–electrophoresis, isoelectric focusing (IEF), miniature
chips, surface plasmon resonance (SPR), protein array, rolling circle
amplification (RCAT), peptidomics},
url = {http://dx.doi.org/10.1002/0470020202.ch11}
}
@ARTICLE{Somervaille2009,
author = {Somervaille, Tim C.P. and Matheny, Christina J. and Spencer, Gary
J. and Iwasaki, Masayuki and Rinn, John L. and Witten, Daniela M.
and Chang, Howard Y. and Shurtleff, Sheila A. and Downing, James
R. and Cleary, Michael L.},
title = {Hierarchical Maintenance of MLL Myeloid Leukemia Stem Cells Employs
a Transcriptional Program Shared with Embryonic Rather Than Adult
Stem Cells},
journal = {Cell Stem Cell},
year = {2009},
volume = {4},
pages = {129--140},
number = {2},
month = feb,
abstract = {Summary The genetic programs that promote retention of self-renewing
leukemia stem cells (LSCs) at the apex of cellular hierarchies in
acute myeloid leukemia (AML) are not known. In a mouse model of human
AML, LSCs exhibit variable frequencies that correlate with the initiating
MLL oncogene and are maintained in a self-renewing state by a transcriptional
subprogram more akin to that of embryonic stem cells (ESCs) than
to that of adult stem cells. The transcription/chromatin regulatory
factors Myb, Hmgb3, and Cbx5 are critical components of the program
and suffice for Hoxa/Meis-independent immortalization of myeloid
progenitors when coexpressed, establishing the cooperative and essential
role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating
MLL/Hox/Meis program. Enriched expression of LSC maintenance and
ESC-like program genes in normal myeloid progenitors and poor-prognosis
human malignancies links the frequency of aberrantly self-renewing
progenitor-like cancer stem cells (CSCs) to prognosis in human cancer.},
issn = {1934-5909},
keywords = {STEMCELL, CELLCYCLE},
url = {http://www.sciencedirect.com/science/article/B8G3V-4VJ5BW9-D/2/f1d27f7058fa303f94a6932ef663b473}
}
@ARTICLE{Sominanda2008,
author = {Sominanda, A and Hillert, J and Fogdell-Hahn, A},
title = {In vivo bioactivity of interferon-beta in multiple sclerosis patients
with neutralising antibodies is titre-dependent},
journal = {J. Neurol. Neurosurg. Psychiatry},
year = {2008},
volume = {79},
pages = {57--62},
number = {1},
month = jan,
abstract = {BackgroundDevelopment of neutralising antibodies (NAbs) against recombinant
interferon-{beta} (IFN{beta}) is a significant clinical problem in
the treatment of multiple sclerosis (MS). Several methods are available
to assess NAbs, but there is a lack of consensus on how the different
NAb titre levels interfere with the efficacy of the drug, especially
in the individual patient. MethodsNAb titres were measured with an
in vitro MxA induction assay and the in vivo IFN{beta} response was
assessed by measuring MxA mRNA expression using real-time PCR. ResultsWe
identified titre levels of NAbs at which the IFN{beta} biological
activity was reduced or abrogated. Patients with NAb titres of up
to 150 TRU/ml (ten times reduction units per ml) still had retained
IFN{beta} bioactivity, whereas greatly reduced levels of IFN{beta}
bioactivity were found in patients with NAbs of 150-600 TRU/ml. Titres
above 600 TRU/ml were associated with loss of IFN{beta} bioactivity.
Similar results were obtained when TRAIL mRNA was used as a marker
of the in vivo response to IFN{beta}. ConclusionThere is a stepwise
loss of IFN{beta} bioactivity with increasing NAb titres and it is
possible to identify functionally critical NAb titre levels that
are useful to support treatment decisions at the individual patient
level.},
url = {http://jnnp.bmj.com/cgi/content/abstract/79/1/57}
}
@ARTICLE{Sommer2009,
author = {Sommer, Sandra and Pudrith, Chas B. and Colvin, Christopher J. and
Coussens, Paul M.},
title = {Mycobacterium avium subspecies paratuberculosis suppresses expression
of IL-12p40 and iNOS genes induced by signalling through CD40 in
bovine monocyte-derived macrophages},
journal = {Veterinary Immunology and Immunopathology},
year = {2009},
volume = {128},
pages = {44--52},
number = {1-3},
month = mar,
abstract = {Mycobacterium avium subspecies paratuberculosis (MAP) is a facultative
intracellular organism that resides in host macrophages. MAP causes
a fatal wasting syndrome in ruminants, typified by granulomatous
enteritis in the small intestine. MAP has also been suspected as
a causative or exacerbating factor in some cases of human Crohn's
disease. In MAP infections, a cytotoxic and proinflammatory Th1-like
response is essential to control disease. While such a response may
initially develop, this typically gives way to a Th2-like response
later in infection. Interaction between CD40 receptors on macrophages
and CD154 (CD40L) on activated T cells is crucial for maintaining
a Th1 response and activation of macrophages. In this report, we
investigated the hypothesis that CD40 signalling is impaired in MAP-infected
macrophages. Uninfected bovine monocyte-derived macrophages (MDM)
responded to CD40L by up-regulating expression of genes encoding
IL-6, TNF[alpha], IL-8, iNOS, IL-10, and IL-12p40. In contrast, MDM
cells infected with MAP failed to up-regulate expression of iNOS
and IL-12p40 genes in response to CD40L. CD40L stimulation caused
a transient activation of the mitogen-activated protein kinase (MAPK)
family member extracellular signal-regulated kinases (ERK) 1/2, stress-activated
protein kinase/Jun N-terminal kinase (SAPK/JNK) and p38 in MDM cells.
In uninfected cells, inhibition of MAPK revealed that CD40L-mediated
increase in IL-6 gene expression was dependent on activation of ERK1/2,
while increases in IL-12p40, iNOS, and IL-10 gene expression were
dependent on activation of p38. Because early activation of p38 was
unimpaired in MAP-infected macrophages, we propose that MAP interferes
with gene expression of iNOS and IL-12p40 genes downstream of p38.},
booktitle = {Special Issue: The 8th International Veterinary Immunology Symposium
(8th IVIS)},
issn = {0165-2427},
keywords = {Mycobacterium avium ssp. paratuberculosis, Macrophage activation,
CD40 signalling, IL-12p40, Inducible NO synthase},
url = {http://www.sciencedirect.com/science/article/B6TD5-4TPF49G-S/2/0c2bf80c53f02bf6e2fba0fac12275eb}
}
@ARTICLE{Sommer2010,
author = {Sommer, Wolfgang H. and Lidström, Jessica and Sun, Hui and Passer,
Derek and Eskay, Robert and Parker, Stephen C.J. and Witt, Stephanie
H. and Zimmermann, Ulrich S. and Nieratschker, Vanessa and Rietschel,
Marcella and Margulies, Elliott H. and Palkovits, Miklós and Laucht,
Manfred and Heilig, Markus},
title = {Human NPY promoter variation rs16147:T>C as a moderator of prefrontal
NPY gene expression and negative affect},
journal = {Hum. Mutat.},
year = {2010},
volume = {31},
pages = {E1594--E1608},
number = {8},
abstract = {Abstract 10.1002/humu.21299.abs Studies in humans and animals suggest
a role for NPY in the mediation of behavioral stress responses. Here,
we examined whether the NPY promoter variant rs16147:T>C is functional
for expression of NPY in a brain region relevant for behavioral control,
anxiety and depression, the anterior cingulate cortex. In silico
analysis of DNA structural profile changes produced by rs16147 variation
suggests allelic differences in protein binding at the rs16147 site.
This was confirmed by electrophoretic mobility shift assay, demonstrating
that the rs16147 C-allele has strongly reduced affinity for a yet
unknown factor compared to the T-allele. Analyzing 107 human post-mortem
brain samples we show that allelic variation at rs16147 contributes
to regulation of NPY mRNA and peptide levels in this region. Specifically,
the C-allele leads to increased gene expression. In agreement with
the molecular findings, rs16147:T>C is associated with anxiety and
depressive symptoms in 314 young adults via a gene x environment
interaction with early childhood adversity, replicating the recent
finding of rs16147-C as a risk factor for stress related psychopathology.
Our results show the importance of rs16147:T>C for regulation of
NPY gene expression and brain function. © 2010 Wiley-Liss, Inc.},
issn = {1098-1004},
keywords = {NPY, promoter variant, brain, gene expression, stress coping},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.21299}
}
@ARTICLE{Son2005,
author = {Son, Chang Gue and Bilke, Sven and Davis, Sean and Greer, Braden
T. and Wei, Jun S. and Whiteford, Craig C. and Chen, Qing-Rong and
Cenacchi, Nicola and Khan, Javed},
title = {Database of mRNA gene expression profiles of multiple human organs},
journal = {Genome Res.},
year = {2005},
volume = {15},
pages = {443--450},
number = {3},
month = mar,
abstract = {Genome-wide expression profiling of normal tissue may facilitate our
understanding of the etiology of diseased organs and augment the
development of new targeted therapeutics. Here, we have developed
a high-density gene expression database of 18,927 unique genes for
158 normal human samples from 19 different organs of 30 different
individuals using DNA microarrays. We report four main findings.
First, despite very diverse sample parameters (e.g., age, ethnicity,
sex, and postmortem interval), the expression profiles belonging
to the same organs cluster together, demonstrating internal stability
of the database. Second, the gene expression profiles reflect major
organ-specific functions on the molecular level, indicating consistency
of our database with known biology. Third, we demonstrate that any
small (i.e., n [~] 100), randomly selected subset of genes can approximately
reproduce the hierarchical clustering of the full data set, suggesting
that the observed differential expression of >90% of the probed genes
is of biological origin. Fourth, we demonstrate a potential application
of this database to cancer research by identifying 19 tumor-specific
genes in neuroblastoma. The selected genes are relatively underexpressed
in all of the organs examined and belong to therapeutically relevant
pathways, making them potential novel diagnostic markers and targets
for therapy. We expect this database will be of utility for developing
rationally designed molecularly targeted therapeutics in diseases
such as cancer, as well as for exploring the functions of genes.},
url = {http://genome.cshlp.org/cgi/content/abstract/15/3/443}
}
@ARTICLE{Son2011,
author = {Ji Woong Son and Kang Jin Jeong and Woo-Sean Jean and Soon Young
Park and Sanghoon Jheon and Hyun Min Cho and Chang Gyo Park and Hoi
Young Lee and Jaeku Kang},
title = {Genome-wide combination profiling of DNA copy number and methylation
for deciphering biomarkers in non-small cell lung cancer patients},
journal = {Cancer Letters},
year = {2011},
volume = {311},
pages = {29 - 37},
number = {1},
abstract = {Early detection of lung cancer provides the highest potential for
saving lives. To date, no routine screening method enabling early
detection is available, which is a key factor in the disease’s
high mortality rate. Copy number changes and DNA methylation alterations
are good indicators of carcinogenesis and cancer prognosis. In this
study, we attempted to combine profiles of DNA copy number and methylation
patterns in 20 paired cancerous and noncancerous tissue samples from
non-small cell lung cancer (NSCLC) patients, and we detected several
clinically important genes with genetic and epigenetic relationships.
Using array comparative genomic hybridization (aCGH), statistically
significant differences were observed across the histological subtypes
for gains at 1p31.1, 3q26.1, and 3q26.31–3q29 as well as for losses
at 1p21.1, 2q33.3, 2q37.3, 3p12.3, 4q35.2, and 13q34 in squamous
cell carcinoma (SQ) patients, and losses at 12q24.33 were measured
in adenocarcinoma (AD) patients (p < 0.05). In an analysis
of DNA methylation at 1505 autosomal CpG loci that are associated
with 807 cancer-related genes, we identified six and nine loci with
higher and lower DNA methylation levels, respectively, in tumor tissue
compared to non-tumor lung tissues from AD patients. In addition,
three loci with higher and seven loci with lower DNA methylation
levels were identified in tumor tissue from SQ patients compared
to non-tumor lung tissue. Subsequently, we searched for regions exhibiting
concomitant hypermethylation and genomic loss in both ADs and SQs.
One clone representing 7p15.2 (which includes candidate genes such
as HOXA9 and HOXA11) and one target ID representing HOXA9_E252_R
were detected. Quantitative real-time PCR identified the potential
candidate gene HOXA9 as being down-regulated in the majority of NSCLC
patients. Moreover, following HOXA9 over-expression, the invasion
of representative cell lines, A549 and HCC95, were significantly
inhibited. Taken together, our results show that the combined profiling
analysis technique is a useful tool for identifying biomarkers in
lung cancer and that HOXA9 might be a potential candidate gene for
the pathogenesis and diagnosis of NSCLC patients.},
doi = {10.1016/j.canlet.2011.06.021},
issn = {0304-3835},
keywords = {Copy number change},
url = {http://www.sciencedirect.com/science/article/pii/S0304383511003661}
}
@ARTICLE{Sonda2010,
author = {Sonda, Sabrina and Morf, Laura and Bottova, Iveta and Baetschmann,
Hansruedi and Rehrauer, Hubert and Caflisch, Amedeo and Hakimi, Mohamed-Ali
and Hehl, Adrian B.},
title = {Epigenetic mechanisms regulate stage differentiation in the minimized
protozoan Giardia lamblia},
journal = {Molecular Microbiology},
year = {2010},
volume = {76},
pages = {48--67},
number = {1},
abstract = {Summary Histone modification is an important mechanism regulating
both gene expression and the establishment and maintenance of cellular
phenotypes during development. Regulation of histone acetylation
via histone acetylases and deacetylases (HDACs) appears to be particularly
crucial in determining gene expression patterns. In this study we
explored the effect of HDAC inhibition on the life cycle of the human
pathogen Giardia lamblia, a highly reduced parasitic protozoan characterized
by minimized cellular processes. We found that the HDAC inhibitor
FR235222 increased the level of histone acetylation and induced transcriptional
regulation of ∼2% of genes in proliferating and encysting parasites.
In addition, our analyses showed that the levels of histone acetylation
decreased during differentiation into cysts, the infective stage
of the parasite. Importantly, FR235222 treatment during encystation
reversed this histone hypo-acetylation and potently blocked the formation
of cysts. These results provide the first direct evidence for epigenetic
regulation of gene expression in this simple eukaryote. This suggests
that regulation of histone acetylation is involved in the control
of Giardia stage differentiation, and identifies epigenetic mechanisms
as a promising target to prevent Giardia transmission.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07062.x}
}
@ARTICLE{Sonderegger2010,
author = {Sonderegger, Stefan and Haslinger, Peter and Sabri, Alia and Leisser,
Christina and Otten, Jan V. and Fiala, Christian and Knofler, Martin},
title = {Wingless (Wnt)-3A Induces Trophoblast Migration and Matrix Metalloproteinase-2
Secretion through Canonical Wnt Signaling and Protein Kinase B/AKT
Activation},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {211--220},
number = {1},
month = jan,
abstract = {Invasion of human trophoblasts is promoted through activation of wingless
(Wnt) signaling, suggesting a role of the pathway in placental development
and morphogenesis. However, details on the process such as involvement
of canonical and/or noncanonical Wnt signaling cascades as well as
their target genes are largely unknown. Hence, signal transduction
via canonical Wnt signaling or phosphatidylinositide 3-kinase (PI3K)/AKT
and their cross talk as well as trophoblast-specific protease expression
were investigated in trophoblastic SGHPL-5 cells and primary extravillous
trophoblasts purified from first-trimester placentas. Western blot
analyses revealed that the recombinant Wnt ligand Wnt-3A increased
phosphorylation of AKT and the downstream kinase glycogen synthase
kinase (GSK)-3{beta} as well as accumulation of activated, nuclear
{beta}-catenin. In accordance, luciferase expression of a canonical
Wnt/TCF reporter and cell migration in first-trimester villous explant
cultures and of SGHPL-5 cells were stimulated. Chemical inhibition
of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3{beta}
and trophoblast motility but did not affect appearance of activated
{beta}-catenin or Wnt/TCF reporter activity. In contrast, inhibition
of the canonical pathway through soluble Dickkopf-1 did not influence
AKT and GSK-3{beta} phosphorylation but reduced Wnt reporter activity,
accumulation of active {beta}-catenin, and cell migration. Both inhibitors
decreased Wnt-3A-induced secretion of pro- and active matrix metalloproteinase-2
from SGHPL-5 cells and pure EVT. The data suggest that Wnt-3A may
activate canonical Wnt signaling and PI3K/AKT through distinct receptors.
The two signaling cascades act independently in trophoblasts; however,
both pathways promote Wnt-dependent migration and the release of
matrix metalloproteinase-2, which has been identified as novel Wnt
target in invasive trophoblasts.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/1/211}
}
@ARTICLE{Sonderegger2007,
author = {Sonderegger, S. and Husslein, H. and Leisser, C. and Knöfler, M.},
title = {Complex Expression Pattern of Wnt Ligands and Frizzled Receptors
in Human Placenta and its Trophoblast Subtypes},
journal = {Placenta},
year = {2007},
volume = {28},
pages = {S97--S102},
number = {Supplement 1},
month = apr,
abstract = {Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous
Wnt ligands was recently shown to play a crucial role in the invasive
differentiation of human trophoblasts. To gain insights into the
expression pattern of the developmental regulators, we analysed all
human Wnt ligands and their frizzled (FZD) receptors in the human
placenta and different trophoblast model systems using semi-quantitative
PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD receptors
were detectable in placental tissues, however, expression patterns
varied with gestational age and between different trophoblast subtypes
suggesting cell-specific functions. Besides Wnt ligands acting through
the canonical pathway, non-canonical ligands such as Wnt-5a, which
may also activate alternative Wnt signalling pathways or inhibit
canonical Wnt signalling, could be identified. Western blot analyses
revealed secretion of Wnt-5a from primary trophoblast cultures and
trophoblastic cell lines. To evaluate the potential role of Wnt-5a,
SGHPL-5 trophoblast cells were transfected with luciferase reporter
plasmids harbouring eight T-cell factor (TCF) DNA-recognition sequences
which are exclusively activated through the canonical Wnt signalling
pathway. Luciferase assays revealed that Wnt-3a-induced reporter
activity was repressed by recombinant Wnt-5a indicating an antagonistic
role in trophoblasts. The data suggest that a complex network of
Wnt ligands and FZD receptors may regulate developmental processes
of the human placenta.},
booktitle = {Trophoblast Research From Bench to Bedside: Comparative, Experimental
and Clinical Aspects},
issn = {0143-4004},
keywords = {Wnt, Frizzled, Placenta, Trophoblast, Differentiation},
url = {http://www.sciencedirect.com/science/article/B6WPD-4MR1P55-1/2/a79a6237c01b80d58baf6ed99b254a78}
}
@ARTICLE{Song2011a,
author = {Song, Chun-Xiao and Szulwach, Keith E and Fu, Ye and Dai, Qing and
Yi, Chengqi and Li, Xuekun and Li, Yujing and Chen, Chih-Hsin and
Zhang, Wen and Jian, Xing and Wang, Jing and Zhang, Li and Looney,
Timothy J and Zhang, Baichen and Godley, Lucy A and Hicks, Leslie
M and Lahn, Bruce T and Jin, Peng and He, Chuan},
title = {Selective chemical labeling reveals the genome-wide distribution
of 5-hydroxymethylcytosine},
journal = {Nat Biotech},
year = {2011},
volume = {29},
pages = {68--72},
number = {1},
month = jan,
comment = {10.1038/nbt.1732},
issn = {1087-0156},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nbt.1732}
}
@ARTICLE{Song2011,
author = {Song, Chun-Yan and Zeng, Xin and Chen, Si-Wen and Hu, Ping-Fang and
Zheng, Zhi-Wu and Ning, Bei-Fang and Shi, Jian and Xie, Wei-Fen and
Chen, Yue-Xiang},
title = {Sophocarpine alleviates non-alcoholic steatohepatitis in rats},
journal = {Journal of Gastroenterology and Hepatology},
year = {2011},
volume = {26},
pages = {765--774},
number = {4},
abstract = {Abstract Background and Aim:  Non-alcoholic steatohepatitis (NASH)
is one entity in the spectrum of non-alcoholic fatty liver disease
(NAFLD). The aim of this study was to explore the prevention and
therapeutic effect of sophocarpine on experimental rat NASH.Methods: 
Sophocarpine with the dosage of 20Â mg/kg/day was injected into NASH
rats. At the end of 12Â weeks, all rats were killed to detect the
degree of fatty degeneration, inflammation and fibrosis.Results: 
Sophocarpine intervention (in the pro-treated and treated groups)
resulted in a significant decrease of liver weight, liver index,
serum transaminase and serum lipids. Messenger RNA expressions of
leptin, interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming
growth factor (TGF)-β1, procollagen-I and α-smooth muscle actin
(SMA) and deposition of IL-6, TNF-α and TGF-β1 in liver decreased,
whereas the messenger RNA expression of adiponectin increased significantly
compared with that in the model group. Moreover, histological improvement
was also observed in the sophocarpine intervention group. In addition,
there was no significant difference in any detected indicator between
the pro-treated and treated group.Conclusions:  Sophocarpine could
decrease the level of serum transaminase, improve lipid metabolism,
reduce synthesis of inflammatory cytokines TNF-α, TGF-β1 and IL-6,
activate protective adipocytokine adiponectin, and might be selected
as a promising agent for the clinical prevention and therapy of NASH.},
doi = {10.1111/j.1440-1746.2010.06561.x},
issn = {1440-1746},
keywords = {adipocytokine, non-alcoholic steatohepatitis, pro-inflammatory cytokine,
sophocarpine},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1440-1746.2010.06561.x}
}
@ARTICLE{Song2010a,
author = {Song, Dongliang and Shen, Junhui and Li, Laigeng},
title = {Characterization of cellulose synthase complexes in Populus xylem
differentiation},
journal = {New Phytologist},
year = {2010},
volume = {187},
pages = {777--790},
number = {3},
abstract = {Summary * •It is generally hypothesized that the synthesis of cellulose
in higher plants is mediated by cellulose synthase complexes (CSCs)
localized on the plasma membrane. However, CSCs have not been investigated
thoroughly through their isolation. The availability of ample Populus
tissue allowed Populus CSCs to be isolated and characterized in association
with xylem differentiation. * •The methods used here included co-immunoprecipitation,
proteomic analysis, laser microdissection, immunolocalization and
others. * •Western blot analysis of the immunoprecipitated CSCs
led to the identification of at least two types of CSC in the membrane
protein of Populus xylem tissue. Proteomic analysis further revealed
that the two types of CSC were assembled from different cellulose
synthase proteins. Immunolocalization confirmed that both types of
CSC were involved in secondary cell wall formation. In addition,
a number of noncellulose synthase proteins were also identified in
association with CSC precipitation. * •The results indicate that
two types of CSC participate in secondary wall formation in Populus,
suggesting a new mechanism of cellulose formation involved in the
thickening of wood cell walls. This study also suggests that the
CSC machinery may be aided by other proteins in addition to cellulose
synthase proteins.},
issn = {1469-8137},
keywords = {cellulose synthase, cellulose synthesis, differentiating xylem, Populus,
primary cell wall, secondary cell walls},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2010.03315.x}
}
@ARTICLE{Song2007,
author = {Song, Eun Sun and Park, Shin Ae and Kim, Su Hee and Cho, Yang Je
and Ahn, Bo Young and Ahn, Byung Cheol and Lee, Na Gyong},
title = {Adjuvant effect of CIA07, a combination of Escherichia coli DNA fragments
and modified lipopolysaccharides, on the immune response to hepatitis
B virus surface antigen},
journal = {FEMS Immunology \& Medical Microbiology},
year = {2007},
volume = {51},
pages = {496--504},
number = {3},
abstract = {Abstract CIA07 is an immunostimulatory agent composed of bacterial
DNA fragments and modified lipopolysaccharide, which has antitumor
activity against bladder cancer in mice. In this study, the adjuvant
activity of CIA07 was evaluated using hepatitis B virus surface antigen
(HBsAg) as the immunogen. Mice were immunized intramuscularly three
times at 1-week intervals with HBsAg alone or in combination with
alum, bacterial DNA fragments, modified lipopolysaccharide, CIA07
or CpG1826, and immune responses were assessed. At 1 week after the
final injection, the HBsAg-specific total serum IgG antibody titer
in CIA07-treated mice was 14 times higher than that in animals administered
antigen alone, six times higher than in mice given alum or bacterial
DNA fragments and twice as high as those treated with modified lipopolysaccharide
or CpG1826, and remained maximal until 8 weeks postimmunization.
Animals receiving antigen alone or plus alum displayed barely detectable
HBsAg-specific serum IgG2a antibody responses. However, coadministration
of CIA07 with antigen led to markedly enhanced serum IgG2a antibody
titer and IFN-γ+ production in splenocytes, indicating that CIA07
effectively induces Th1-type immune responses. In addition, the number
of HBsAg-specific CD8+ T cells in peripheral blood mononuclear cells
was elevated in CIA07-treated mice. These data clearly demonstrate
that CIA07 is able to induce both cellular and humoral immune responses
to HBsAg, and confirm its potential as an adjuvant in therapeutic
vaccines for hepatitis B virus infections.},
issn = {1574-695X},
keywords = {adjuvant, hepatitis B surface antigen, antibody response, cellular
immune response},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-695X.2007.00325.x}
}
@ARTICLE{Song2009,
author = {Song, Fengju and Zheng, Hong and Liu, Ben and Wei, Sheng and Dai,
Hongji and Zhang, Lina and Calin, George A. and Hao, Xishan and Wei,
Qingyi and Zhang, Wei and Chen, Kexin},
title = {An miR-502-Binding Site Single-Nucleotide Polymorphism in the 3'-Untranslated
Region of the SET8 Gene Is Associated with Early Age of Breast Cancer
Onset},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {6292--6300},
number = {19},
month = oct,
abstract = {Purpose: MicroRNAs regulate gene expression by binding to the 3'-untranslated
region (UTR) of target genes. Single-nucleotide polymorphisms of
critical genes may affect their regulation by microRNAs. We have
identified a single-nucleotide polymorphism within the miR-502 seed
binding region in the 3'-UTR of the SET8 gene. SET8 methylates TP53
and regulates genome stability. We investigated the role of this
SET8 single-nucleotide polymorphism and in concert with the TP53
codon 72 single-nucleotide polymorphism in the propensity for onset
of breast cancer. Experimental Design: We measured the SET8 single-nucleotide
polymorphisms in a case-control study on 1,110 breast cancer cases
and 1,097 controls. Results: The SET8 CC and TP53 GG genotypes were
independently associated with an earlier age of breast cancer onset
in an allele-dose-dependent manner (for SET8, 52.2 years for TT,
51.4 for TC, and 49.5 for CC; and for TP53, 53.1 years for CC, 51.5
for GC, 50.7 for GG). Individuals with combined SET8 CC and TP53
GG genotypes developed cancer at a median age of 47.7 years as compared
with 54.6 years for individuals with combined SET8 TT and TP53 CC
genotypes. In the 51 breast cancer tissue samples tested, the SET8
CC genotype was associated with reduced SET8, but not miR-502, transcript
levels. Conclusions: These data suggest that the miR-502-binding
site single-nucleotide polymorphism in the 3'-UTR of SET8 modulates
SET8 expression and contributes to the early development of breast
cancer, either independently or together with the TP53 codon 72 single-nucleotide
polymorphism. Larger studies with multiethnic groups are warranted
to validate our findings. (Clin Cancer Res 2009;15(19):6292-300)},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/19/6292}
}
@ARTICLE{Song2010,
author = {Song, Guisheng and Sharma, Amar Deep and Roll, Garrett R. and Ng,
Raymond and Lee, Andrew Y. and Blelloch, Robert H. and Frandsen,
Niels M. and Willenbring, Holger},
title = {MicroRNAs control hepatocyte proliferation during liver regeneration},
journal = {Hepatology},
year = {2010},
volume = {51},
pages = {1735--1743},
number = {5},
abstract = {Abstract MicroRNAs (miRNAs) constitute a new class of regulators of
gene expression. Among other actions, miRNAs have been shown to control
cell proliferation in development and cancer. However, whether miRNAs
regulate hepatocyte proliferation during liver regeneration is unknown.
We addressed this question by performing 2/3 partial hepatectomy
(2/3 PH) on mice with hepatocyte-specific inactivation of DiGeorge
syndrome critical region gene 8 (DGCR8), an essential component of
the miRNA processing pathway. Hepatocytes of these mice were miRNA-deficient
and exhibited a delay in cell cycle progression involving the G1
to S phase transition. Examination of livers of wildtype mice after
2/3 PH revealed differential expression of a subset of miRNAs, notably
an induction of miR-21 and repression of miR-378. We further discovered
that miR-21 directly inhibits Btg2, a cell cycle inhibitor that prevents
activation of forkhead box M1 (FoxM1), which is essential for DNA
synthesis in hepatocytes after 2/3 PH. In addition, we found that
miR-378 directly inhibits ornithine decarboxylase (Odc1), which is
known to promote DNA synthesis in hepatocytes after 2/3 PH. Conclusion:
Our results show that miRNAs are critical regulators of hepatocyte
proliferation during liver regeneration. Because these miRNAs and
target gene interactions are conserved, our findings may also be
relevant to human liver regeneration. (HEPATOLOGY 2010)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.23547}
}
@ARTICLE{Song2009a,
author = {Song, H and Bergstrasser, C and Rafat, N and Höger, S and Schmidt,
M and Endres, N and Goebeler, M and Hillebrands, JL and Brigelius-Flohé,
R and Banning, A and Beck, G and Loesel, R and Yard, BA},
title = {The carbon monoxide releasing molecule (CORM-3) inhibits expression
of vascular cell adhesion molecule-1 and E-selectin independently
of haem oxygenase-1 expression},
journal = {British Journal of Pharmacology},
year = {2009},
volume = {157},
pages = {769--780},
number = {5},
abstract = {Background and purpose:  Although carbon monoxide (CO) can modulate
inflammatory processes, the influence of CO on adhesion molecules
is less clear. This might be due to the limited amount of CO generated
by haem degradation. We therefore tested the ability of a CO releasing
molecule (CORM-3), used in supra-physiological concentrations, to
modulate the expression of vascular cell adhesion molecule (VCAM)-1
and E-selectin on endothelial cells and the mechanism(s) involved.
Experimental approach:  Human umbilical vein endothelial cells
(HUVECs) were stimulated with tumour necrosis factor (TNF)-α in
the presence or absence of CORM-3. The influence of CORM-3 on VCAM-1
and E-selectin expression and the nuclear factor (NF)-κB pathway
was assessed by flow cytometry, Western blotting and electrophoretic
mobility shift assay. Key results:  CORM-3 inhibited the expression
of VCAM-1 and E-selectin on TNF-α-stimulated HUVEC. VCAM-1 expression
was also inhibited when CORM-3 was added 24 h after TNF-α stimulation
or when TNF-α was removed. This was paralleled by deactivation of
NF-κB and a reduction in VCAM-1 mRNA. Although TNF-α removal was
more effective in this regard, VCAM-1 protein was down-regulated
more rapidly when CORM-3 was added. CORM-3 induced haem oxygenase-1
(HO-1) in a dose- and time-dependent manner, mediated by the transcription
factor, Nrf2. CORM-3 was still able to down-regulate VCAM-1 expression
in HUVEC transfected with siRNA for HO-1 or Nrf2. Conclusions and
implications:  Down-regulation of VCAM and E-selectin expression
induced by CORM-3 was independent of HO-1 up-regulation and was predominantly
due to inhibition of sustained NF-κB activation.},
issn = {1476-5381},
keywords = {endothelial cells, adhesion molecules, inflammation, carbon monoxide},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1476-5381.2009.00215.x}
}
@ARTICLE{Song2006,
author = {Song, Jin and Jie, Chunfa and Polk, Paula and Shridhar, Ravi and
Clair, Timothy and Zhang, Jun and Yin, Lijia and Keppler, Daniel},
title = {The candidate tumor suppressor CST6 alters the gene expression profile
of human breast carcinoma cells: Down-regulation of the potent mitogenic,
motogenic, and angiogenic factor autotaxin},
journal = {Biochemical and Biophysical Research Communications},
year = {2006},
volume = {340},
pages = {175--182},
number = {1},
month = feb,
abstract = {We recently coined CST6 as a novel candidate tumor suppressor gene
for breast cancer. CST6 indeed is expressed in the normal human breast
epithelium, but little or not at all in breast carcinomas and breast
cancer cell lines. Moreover, ectopic expression of CST6 in human
breast cancer cells suppressed cell proliferation, migration, invasion,
and orthotopic tumor growth. To obtain insights into the molecular
mechanism by which CST6 exhibits its pleiotropic effects on tumor
cells, we compared global gene expression profiles in mock- and CST6-transfected
human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed
altered expression. These included genes for extracellular matrix
components, cytokines, kinases, and phosphatases, as well as several
key transcription factors. TaqMan PCR assays were used to confirm
the microarray data for 7 out of 11 genes. One down-regulated gene
product, secreted autotaxin/lyso-phospholipase D, was of particular
interest because its down-regulation by CST6 could explain most of
CST6's effect on the breast cancer cells. This study thus provides
the first evidence that CST6 plays a role in the modulation of genes,
particularly, genes that are highly relevant to breast cancer progression.},
issn = {0006-291X},
keywords = {Tumor suppressors, Cytokines, Signaling, DNA microarrays, Functional
genomics, Breast cancer},
url = {http://www.sciencedirect.com/science/article/B6WBK-4HS39N3-4/2/91a2b24a5c7702ec2ec282322af1ffdd}
}
@ARTICLE{Song2009b,
author = {Song, Min Ok and Li, Jianying and Freedman, Jonathan H.},
title = {Physiological and toxicological transcriptome changes in HepG2 cells
exposed to copper},
journal = {Physiol Genomics},
year = {2009},
volume = {38},
pages = {386--401},
number = {3},
month = aug,
abstract = {Copper is an essential trace element; however, at supraphysiological
levels, it can be extremely toxic. Microarray data from HepG2 cells
exposed to 100, 200, 400, and 600 {micro}M copper for 4, 8, 12 and
24 h were generated and analyzed. Principal components, K-means,
and hierarchical clustering, interactome, and pathway mapping analyses
indicated that these exposure conditions induce physiological and
toxicological changes in the HepG2 transcriptome. As a general trend,
when the level of toxicity increases, the number and diversity of
affected genes, Gene Ontology categories, regulatory pathways, and
complexity of interactomes increase. Physiological responses to copper
include transition metal ion binding and responses to stress/stimulus,
whereas toxicological responses include apoptosis, morphogenesis,
and negative regulation of biomolecule metabolism. The global gene
expression profile was overlaid onto biomolecular interaction networks
and signal transduction cascades using pathway mapping and interactome
identification. This analysis indicated that copper modulates signal
transduction pathways associated with MAPK, NF-{kappa}B, death receptor,
IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein
ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement
and coagulation, and sonic hedgehog signaling. These results provide
insights into the global and molecular mechanisms regulating the
physiological and toxicological responses to metal exposure.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/38/3/386}
}
@ARTICLE{Song2011c,
author = {Renfang Song and Graeme Preston and Ihor V. Yosypiv},
title = {Angiotensin II stimulates in vitro branching morphogenesis of the
isolated ureteric bud},
journal = {Mechanisms of Development},
year = {2011},
volume = {128},
pages = {359 - 367},
number = {7–10},
abstract = {Mutations in the renin–angiotensin system (RAS) genes are associated
with congenital anomalies of the kidney and urinary tract (CAKUT).
As angiotensin (Ang) II, the principal effector peptide growth factor
of the RAS, stimulates ureteric bud (UB) branching in whole intact
embryonic (E) metanephroi, defects in UB morphogenesis may be causally
linked to CAKUT observed under conditions of disrupted RAS. In the
present study, using the isolated intact UB (iUB) assay, we tested
the hypothesis that Ang II stimulates UB morphogenesis by directly
acting on the UB, identified Ang II target genes in the iUB by microarray
and examined the effect of Ang II on UB cell migration in vitro.
We show that isolated E11.5 mouse iUBs express Ang II AT1 and AT2
receptor mRNA. Treatment of E11.5 iUBs grown in collagen matrix gels
with Ang II (10−5 M) increases the number of iUB tips after
48 h of culture compared to control (4.8 ± 0.4 vs.
2.4 ± 0.2, p < 0.01). A number of genes required
for UB branching as well as novel genes whose role in UB development
is currently unknown are targets of Ang II signaling in the iUB.
In addition, Ang II increases UB cell migration (346 ± 5.1
vs. 275 ± 4.4, p < 0.01) in vitro. In summary,
Ang II stimulates UB cell migration and directly induces morphogenetic
response in the iUB. We conclude that Ang II-regulated genes in the
iUB may be important mediators of Ang II-induced UB branching. We
hypothesize that Ang II-dependent cell movements play an important
role in UB branching morphogenesis.},
doi = {10.1016/j.mod.2011.07.002},
issn = {0925-4773},
keywords = {Kidney development},
url = {http://www.sciencedirect.com/science/article/pii/S092547731100089X}
}
@ARTICLE{Song2007a,
author = {Song, Ruo-Hua and D. Tortorella, Micky and Malfait, Anne-Marie and
Alston, James T. and Yang, Zhiyong and Arner, Elizabeth C. and Griggs,
David W.},
title = {Aggrecan degradation in human articular cartilage explants is mediated
by both ADAMTS-4 and ADAMTS-5},
journal = {Arthritis \& Rheumatism},
year = {2007},
volume = {56},
pages = {575--585},
number = {2},
abstract = {Abstract 10.1002/art.22334.abs Objective Recent published studies
have shown that cartilage from ADAMTS-5–knockout mice, but not
ADAMTS-4– or ADAMTS-1–knockout mice, is significantly protected
from degradation. The present study was undertaken to evaluate the
respective roles of these enzymes in human cartilage breakdown, using
a small interfering RNA (siRNA) approach to assess the effects of
inhibition of each enzyme in normal and osteoarthritic (OA) explants.
Methods The activities of siRNA specifically targeting ADAMTS-1,
-4, and -5 were assessed by transfection into primary human chondrocytes
and cultured human cartilage explants. At 24 hours, a cytokine stimulus
was applied to normal, but not OA, samples to initiate a catabolic
response. At designated times, total RNA was isolated and gene expression
was measured by quantitative real-time reverse transcription–polymerase
chain reaction. Aggrecan release and aggrecanase-generated neoepitope
formation were determined by dye binding analysis and Western blotting,
respectively. Results Human chondrocytes and explants were efficiently
transfected with siRNA that specifically decreased the expression
of each targeted gene. Suppression of ADAMTS-4 and ADAMTS-5, individually
or in combination, attenuated the degradation of aggrecan in cytokine-stimulated
normal cartilage. A reduction in aggrecan degradation was also observed
following siRNA-mediated knockdown of either gene in unstimulated
OA cartilage. In contrast, knockdown of ADAMTS-1 failed to inhibit
aggrecan loss. Conclusion Despite the apparent dominant role of ADAMTS-5
in genetically modified mice, our data suggest that both ADAMTS-4
and ADAMTS-5 contribute to the structural damage that characterizes
human OA.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.22334}
}
@ARTICLE{Song2011b,
author = {Song, Shaoming and Abdelmohsen, Kotb and Zhang, Yongqing and Becker,
Kevin G. and Gorospe, Myriam and Bernier, Michel},
title = {Impact of Pyrrolidine Dithiocarbamate and Interleukin-6 on Mammalian
Target of Rapamycin Complex 1 Regulation and Global Protein Translation},
journal = {J. Pharmacol. Exp. Ther.},
year = {2011},
volume = {339},
pages = {905-913},
number = {3},
abstract = {Interleukin-6 (IL-6) is a proinflammatory cytokine that exerts a wide
range of cellular, physiological, and pathophysiological responses.
Pyrrolidine dithiocarbamate (PDTC) antagonizes the cellular responsiveness
to IL-6 through impairment in signal transducer and activator of
transcription-3 activation and downstream signaling. To further elucidate
the biological properties of PDTC, global gene expression profiling
of human HepG2 hepatocellular carcinoma cells was carried out after
treatment with PDTC or IL-6 for up to 8 h. Through an unbiased pathway
analysis method, gene array analysis showed dramatic and temporal
differences in expression changes in response to PDTC versus IL-6.
A significant number of genes associated with metabolic pathways,
inflammation, translation, and mitochondrial function were changed,
with ribosomal protein genes and DNA damage-inducible transcript
4 protein (DDIT4) primarily up-regulated with PDTC but down-regulated
with IL-6. Quantitative polymerase chain reaction and Western blot
analyses validated the microarray data and showed the reciprocal
expression pattern of the mammalian target of rapamycin (mTOR)-negative
regulator DDIT4 in response to PDTC versus IL-6. Cell treatment with
PDTC resulted in a rapid and sustained activation of Akt and subsequently
blocked the IL-6-mediated increase in mTOR complex 1 function through
up-regulation in DDIT4 expression. Conversely, down-regulation of
DDIT4 with small interfering RNA dampened the capacity of PDTC to
block IL-6-dependent mTOR activation. The overall protein biosynthetic
capacity of the cells was severely blunted by IL-6 but increased
in a rapamycin-independent pathway by PDTC. These results demonstrate
a critical effect of PDTC on mTOR complex 1 function and provide
evidence that PDTC can reverse IL-6-related signaling via induction
of DDIT4.},
doi = {10.1124/jpet.111.185678},
eprint = {http://jpet.aspetjournals.org/cgi/reprint/339/3/905.pdf},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/339/3/905}
}
@ARTICLE{Song2009c,
author = {Song, Xuewen and Di Giovanni, Valeria and He, Ning and Wang, Kairong
and Ingram, Alistair and Rosenblum, Norman D. and Pei, York},
title = {Systems biology of autosomal dominant polycystic kidney disease (ADPKD):
computational identification of gene expression pathways and integrated
regulatory networks},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {2328--2343},
number = {13},
month = jul,
abstract = {To elucidate the molecular pathways that modulate renal cyst growth
in ADPKD, we performed global gene profiling on cysts of different
size (<1 ml, n = 5; 10-20 ml, n = 5; >50 ml, n = 3) and minimally
cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys
using Affymetrix HG-U133 Plus 2.0 arrays. We used gene set enrichment
analysis to identify overrepresented signaling pathways and key transcription
factors (TFs) between cysts and MCT. We found down-regulation of
kidney epithelial restricted genes (e.g. nephron segment-specific
markers and cilia-associated cystic genes such as HNF1B, PKHD1, IFT88
and CYS1) in the renal cysts. On the other hand, PKD1 cysts displayed
a rich profile of gene sets associated with renal development, mitogen-mediated
proliferation, cell cycle progression, epithelial-mesenchymal transition,
hypoxia, aging and immune/inflammatory responses. Notably, our data
suggest that up-regulation of Wnt/beta-catenin, pleiotropic growth
factor/receptor tyrosine kinase (e.g. IGF/IGF1R, FGF/FGFR, EGF/EGFR,
VEGF/VEGFR), G-protein-coupled receptor (e.g. PTGER2) signaling was
associated with renal cystic growth. By integrating these pathways
with a number of dysregulated networks of TFs (e.g. SRF, MYC, E2F1,
CREB1, LEF1, TCF7, HNF1B/ HNF1A and HNF4A), our data suggest that
epithelial dedifferentiation accompanied by aberrant activation and
cross-talk of specific signaling pathways may be required for PKD1
cyst growth and disease progression. Pharmacological modulation of
some of these signaling pathways may provide a potential therapeutic
strategy for ADPKD.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/13/2328}
}
@ARTICLE{Sonis2007,
author = {Sonis, S. and Haddad, R. and Posner, M. and Watkins, B. and Fey,
E. and Morgan, T.V. and Mookanamparambil, L. and Ramoni, M.},
title = {Gene expression changes in peripheral blood cells provide insight
into the biological mechanisms associated with regimen-related toxicities
in patients being treated for head and neck cancers},
journal = {Oral Oncology},
year = {2007},
volume = {43},
pages = {289--300},
number = {3},
month = mar,
abstract = {Summary Patients treated with radiotherapy are prone to a constellation
of local and systemic toxicities including mucositis, xerostomia,
fatigue and anorexia. The biological complexities and similarities
underlying the development of toxicities have recently been realized.
Mucosal barrier injury is one of the best studied, and gene expression
patterns, based on animal tissue samples, have added to its understanding.
While investigations gene expression based on tissue samples was
valuable, its use precludes more generalizable conclusions relative
to common pathogenic mechanisms. Additionally, attempting to define
the kinetics of changes in gene expression by sequential sampling
is pragmatically unrealistic. Our objectives were: 1. to determine
if changes in gene expression could be detected during toxicity development
using PBM from patients receiving chemoradiation; 2. to characterize
the relationship of expressed genes using graph theory and pathway
analysis; and 3. to evaluate potential relationships between the
expression of particular genes, canonical pathways, and functional
networks in explaining the pathogenesis of regimen-related toxicities.DESIGN:
Microarray analysis was performed using PBM-derived cRNA obtained
before and 2 weeks after the initiation of chemoradiation in five
patients with head and neck cancer who developed documented regimen-related
toxicities. We created a database of those genes newly expressed
at 2 weeks and evaluated their potential significance relative to
toxicity, by canonical pathway analysis, compilation of regional
networks around focus genes, and development of a model globalizing
the individual functional networks. There was strong concordance
between known pathogenic mechanisms of toxicity and the genes, pathways,
and networks developed by our data. A role was elicited for unsuspected
genes in toxicity development. Our results support the concept that
radiation induced toxicities have common underlying mechanisms and
demonstrate the utility of PBM as an RNA source for genetic studies.
This methodology could be broadly applicable to the study of regimen-related
toxicities.},
issn = {1368-8375},
keywords = {Gene expression, Radiation, Toxicity, Head and neck cancer},
url = {http://www.sciencedirect.com/science/article/B6TB6-4KPNHSG-3/2/98364ea00a61d18385bf44f89f88c07f}
}
@ARTICLE{Sonne2009,
author = {Sonne, Si Brask and Almstrup, Kristian and Dalgaard, Marlene and
Juncker, Agnieszka Sierakowska and Edsgard, Daniel and Ruban, Ludmila
and Harrison, Neil J. and Schwager, Christian and Abdollahi, Amir
and Huber, Peter E. and Brunak, Soren and Gjerdrum, Lise Mette and
Moore, Harry D. and Andrews, Peter W. and Skakkebaek, Niels E. and
Meyts, Ewa Rajpert-De and Leffers, Henrik},
title = {Analysis of Gene Expression Profiles of Microdissected Cell Populations
Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {5241--5250},
number = {12},
month = jun,
abstract = {Testicular germ cell cancers in young adult men derive from a precursor
lesion called carcinoma in situ (CIS) of the testis. CIS cells were
suggested to arise from primordial germ cells or gonocytes. However,
direct studies on purified samples of CIS cells are lacking. To overcome
this problem, we performed laser microdissection of CIS cells. Highly
enriched cell populations were obtained and subjected to gene expression
analysis. The expression profile of CIS cells was compared with microdissected
gonocytes, oogonia, and cultured embryonic stem cells with and without
genomic aberrations. Three samples of each tissue type were used
for the analyses. Unique expression patterns for these developmentally
very related cell types revealed that CIS cells were very similar
to gonocytes because only five genes distinguished these two cell
types. We did not find indications that CIS was derived from a meiotic
cell, and the similarity to embryonic stem cells was modest compared
with gonocytes. Thus, we provide new evidence that the molecular
phenotype of CIS cells is similar to that of gonocytes. Our data
are in line with the idea that CIS cells may be gonocytes that survived
in the postnatal testis. We speculate that disturbed development
of somatic cells in the fetal testis may play a role in allowing
undifferentiated cells to survive in the postnatal testes. The further
development of CIS into invasive germ cell tumors may depend on signals
from their postpubertal niche of somatic cells, including hormones
and growth factors from Leydig and Sertoli cells. [Cancer Res 2009;69(12):5241-50]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/12/5241}
}
@ARTICLE{Sonnleitner2011,
author = {Sonnleitner, Elisabeth and Gonzalez, Nicolas and Sorger-Domenigg,
Theresa and Heeb, Stephan and Richter, Andreas S. and Backofen, Rolf
and Williams, Paul and Hüttenhofer, Alexander and Haas, Dieter and
Bläsi, Udo},
title = {The small RNA PhrS stimulates synthesis of the Pseudomonas aeruginosa
quinolone signal},
journal = {Molecular Microbiology},
year = {2011},
volume = {80},
pages = {868--885},
number = {4},
abstract = {Summary Quorum sensing, a cell-to-cell communication system based
on small signal molecules, is employed by the human pathogen Pseudomonas
aeruginosa to regulate virulence and biofilm development. Moreover,
regulation by small trans-encoded RNAs has become a focal issue in
studies of virulence gene expression of bacterial pathogens. In this
study, we have identified the small RNA PhrS as an activator of PqsR
synthesis, one of the key quorum-sensing regulators in P. aeruginosa.
Genetic studies revealed a novel mode of regulation by a sRNA, whereby
PhrS uses a base-pairing mechanism to activate a short upstream open
reading frame to which the pqsR gene is translationally coupled.
Expression of phrS requires the oxygen-responsive regulator ANR.
Thus, PhrS is the first bacterial sRNA that provides a regulatory
link between oxygen availability and quorum sensing, which may impact
on oxygen-limited growth in P. aeruginosa biofilms.},
doi = {10.1111/j.1365-2958.2011.07620.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2011.07620.x}
}
@ARTICLE{Sontag2009,
author = {Sontag, Werner and Kruglikov, Ilja L.},
title = {Expression of Heat Shock Proteins after Ultrasound Exposure in HL-60
Cells},
journal = {Ultrasound in Medicine \& Biology},
year = {2009},
volume = {35},
pages = {1032--1041},
number = {6},
month = jun,
abstract = {One of the important cellular defense mechanisms against stress is
the induction of heat shock proteins (HSPs). We have recently demonstrated
that a low frequency electromagnetic field is unable to induce the
heat shock response (HSR). In the present study, we expanded our
investigations to the induction of HSPs, particularly Hsp72, by ultrasound
(US). Human promyelocytic leukemia HL-60 cells were exposed in suspension
to US at 1, 3 and 10 MHz, as well as combinations of two of these
frequencies. The ability of US to induce Hsp72 was tested for different
frequencies, intensities and exposure times. In addition, the water
bath temperature was varied from 30 to 36°C. The Hsp72 protein expression
was determined 4 and 24 h after treatment. We found that the amount
of Hsp72 increased with increasing US frequency, reaching its highest
level of about 1800%, induced by 10 MHz. After increasing the temperature
of the water bath, the amount of Hsp72 in the treated cells was also
increased, whereas no induction was observed at 30°C. For all treatment
conditions, ultrasound of 1 MHz was unable to significantly induce
Hsp72. At 10 MHz, the exposure time was varied from 0 to 20 min.
We found that the induction of Hsp72 took place after 5 min of exposure.
For a fixed level of absorbed US energy, the continuous regime, as
well as a pulsation of 1:2 (5 ms on and 5 ms off) induced the same
Hsp72 level. Pulsation of 1:5 (2 ms on and 8 ms off) and 1:10 (1
ms on and 9 ms off) did not show any effect. A single sonication
of 20 min, as well as a fractionated sonication of two 10 min exposures
induced the same level of Hsp72, whereas four exposures of 5 min
reduced the Hsp72 level. At the optimum exposure conditions (10 MHz,
10 min), the concentration of other HSPs was also determined. Hsp27
showed no effect but Hsp32, Hsp40 and Hsp72 were induced. Taken together,
these results suggest a synergistic interaction between heat and
US. (E-mail: werner.sontag@ibg.fzk.de)},
issn = {0301-5629},
keywords = {Ultrasound, Mammalian cells, Induction, Heat shock proteins, Heat},
url = {http://www.sciencedirect.com/science/article/B6TD2-4VTVJW1-3/2/13eb4a77078269edb773530660a194d9}
}
@ARTICLE{Soo2011,
author = {Soo, Julia K. and MacKenzie Ross, Alastair D. and Kallenberg, David
M. and Milagre, Carla and Heung Chong, W. and Chow, Jade and Hill,
Lucy and Hoare, Stacey and Collinson, Rebecca S. and Hossain, Mehnaz
and Keith, W. Nicol and Marais, Richard and Bennett, Dorothy C.},
title = {Malignancy without immortality? Cellular immortalization as a possible
late event in melanoma progression},
journal = {Pigment Cell \& Melanoma Research},
year = {2011},
volume = {24},
pages = {490--503},
number = {3},
abstract = {Summary Cell senescence is a permanent growth arrest following extended
proliferation. Cultured cancer cells including metastatic melanoma
cells often appear immortal (proliferate indefinitely), while uncultured
benign nevi (moles) show senescence markers. Here, with new explantation
methods, we investigated which classes of primary pigmented lesions
are typically immortal. Nevi yielded a few proliferating cells, consistent
with most nevus cells being senescent. No nevus culture (0/28) appeared
immortal. Some thin and thick melanoma cultures proved immortal under
these conditions, but surprisingly few (4/37). All arrested cultures
displayed three senescence markers in some cells: β-galactosidase,
nuclear p16, and heterochromatic foci/aggregates. However, melanoma
cultures also showed features of telomeric crisis (arrest because
of ultrashort telomeres). Moreover, crisis markers including anaphase
bridges were frequent in uncultured vertical growth-phase (VGP) melanomas.
Conversely, all immortal melanoma cultures expressed telomerase reverse
transcriptase and telomerase, showing aneuploidy. The findings suggest
that primary melanomas are typically precrisis, with immortalization/telomere
maintenance as a late event.},
doi = {10.1111/j.1755-148X.2011.00850.x},
issn = {1755-148X},
keywords = {cell senescence, crisis, immortalization, primary melanoma, radial
growth-phase, nevus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-148X.2011.00850.x}
}
@ARTICLE{Sood2006,
author = {Sood, Raman and English, Milton A. and Jones, MaryPat and Mullikin,
James and Wang, Duen-Mei and Anderson, Maria and Wu, Dongying and
Chandrasekharappa, Settara C. and Yu, Jun and Zhang, Jinghui and
Paul Liu, P.},
title = {Methods for reverse genetic screening in zebrafish by resequencing
and TILLING},
journal = {Methods},
year = {2006},
volume = {39},
pages = {220--227},
number = {3},
month = jul,
abstract = {Animal models provide an in vivo system to study gene function by
transgenic and knockout approaches. Targeted knockout approaches
have been very successful in mice, but are currently not feasible
in zebrafish due to the inability to grow embryonic stem cells. As
an alternative, a reverse genetic approach that utilizes screening
by resequencing and/or TILLING (Targeting Induced Local Lesions IN
Genomes) of mutagenized genomes has recently gained popularity in
the zebrafish field. Spermatogonia of healthy males are mutagenized
using ENU (N-ethyl-N-nitrosourea) and F1 progeny is collected by
breeding treated males with healthy wild type females. Sperm and
DNA banks are generated from F1 males. DNA is screened for ENU-induced
mutations by sequencing or TILLING. These mutations can then be studied
by in vitro fertilization (IVF) from the cryopreserved sperm of the
corresponding F1 male followed by breeding to homozygosity. A high-throughput
method of screening for rare heterozygotes and efficient recovery
of mutant lines are important in identification of a large number
of mutations using this approach. This article provides optimized
protocols for resequencing and TILLING based on our experiences.
We performed a pilot screen on 1235 F1 males by resequencing 54 exons
from 17 genes and analyzed the sequencing data using multiple programs
to maximize the mutation detection with minimal false positive detection.
As an alternative to sequencing, we developed the protocols for TILLING
by capillary electrophoresis using an ABI Genetic analyzer 3100 platform
followed by fragment analysis using GeneScan and Genotyper softwares.
PCR products generated by fluorescently labeled universal primers
and tailed exon-specific primers were pooled 4-fold prior to heteroduplex
formation. Overall, our pilot screen shows that a combination of
TILLING and sequencing is optimal for achieving cost-effective, high-throughput
screening of a large number of samples. Amplicons with fewer common
SNPs are ideal for TILLING whereas amplicons with multiple SNPs and
in/del polymorphisms are best suited for sequencing followed by analysis
with SNPdetector.},
booktitle = {Zebrafish as a Model for Development},
issn = {1046-2023},
keywords = {Resequencing, TILLING, SNPdetector, Zebrafish, ENU mutagenesis, Testes
cryopreservation},
url = {http://www.sciencedirect.com/science/article/B6WN5-4KMHV46-8/2/54fa9ae8fbe84e8927dbed9694e0346e}
}
@ARTICLE{Soon2009,
author = {Soon, P S H and Gill, A J and Benn, D E and Clarkson, A and Robinson,
B G and McDonald, K L and Sidhu, S B},
title = {Microarray gene expression and immunohistochemistry analyses of adrenocortical
tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas
from adenomas},
journal = {Endocr. Relat. Cancer},
year = {2009},
volume = {16},
pages = {573--583},
number = {2},
month = jun,
abstract = {The management of adrenocortical tumors (ACTs) is complex. The Weiss
score is the present most widely used system for ACT diagnosis. An
ACT is scored from 0 to 9, with a higher score correlating with increased
malignancy. However, ACTs with a score of 3 can be phenotypically
benign or malignant. Our objective is to use microarray profiling
of a cohort of adrenocortical carcinomas (ACCs) and adrenocortical
adenomas (ACAs) to identify discriminatory genes that could be used
as an adjunct to the Weiss score. A cohort of Weiss score defined
ACCs and ACAs were profiled using Affymetrix HGU133plus2.0 genechips.
Genes with high-discriminatory power were identified by univariate
and multivariate analyses and confirmed by quantitative real-time
reverse transcription PCR and immunohistochemistry (IHC). The expression
of IGF2, MAD2L1, and CCNB1 were significantly higher in ACCs compared
with ACAs while ABLIM1, NAV3, SEPT4, and RPRM were significantly
lower. Several proteins, including IGF2, MAD2L1, CCNB1, and Ki-67
had high-diagnostic accuracy in differentiating ACCs from ACAs. The
best results, however, were obtained with a combination of IGF2 and
Ki-67, with 96% sensitivity and 100% specificity in diagnosing ACCs.
Microarray gene expression profiling accurately differentiates ACCs
from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate
in distinguishing between the two groups and is particularly helpful
in ACTs with Weiss score of 3.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/16/2/573}
}
@ARTICLE{Soon2009a,
author = {Soon, Patsy Siok Hwa and Tacon, Lyndal J. and Gill, Anthony J. and
Bambach, Christopher P. and Sywak, Mark S. and Campbell, Peter R.
and Yeh, Michael W. and Wong, Steven G. and Clifton-Bligh, Roderick
J. and Robinson, Bruce G. and Sidhu, Stan B.},
title = {miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis
in Adrenocortical Cancer},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {7684--7692},
number = {24},
month = dec,
abstract = {Purpose: Adrenocortical adenomas are common, whereas adrenocortical
carcinomas are rare. Discriminating between benign and malignant
adrenocortical tumors using conventional histology can be difficult.
In addition, adrenocortical carcinomas generally have poor prognosis
and limited treatment options. MicroRNAs are short noncoding RNAs
that are involved in regulation of gene transcription. Experimental
Design: To identify microRNAs involved in the pathogenesis of adrenocortical
tumors, expression profiling of microRNAs was done on a cohort of
22 adrenocortical carcinomas, 27 adrenocortical adenomas, and 6 normal
adrenal cortices. Results: Twenty-three microRNAs were found to be
significantly differentially expressed between adrenocortical carcinomas
and adrenocortical adenomas. miR-335 and miR-195 were significantly
downregulated in adrenocortical carcinomas compared with adrenocortical
adenomas. This result was further validated in an external cohort
of six adrenocortical carcinomas and four adrenocortical adenomas.
Using Kaplan-Meier analysis, downregulation of miR-195 and upregulation
of miR-483-5p in adrenocortical carcinomas were significantly associated
with poorer disease-specific survival. Conclusions: These findings
indicate that deregulation of microRNAs is a recurring event in human
adrenocortical carcinomas and that aberrant expression of miR-195
and miR-483-5p identifies a subset of poorer prognosis adrenocortical
carcinomas. (Clin Cancer Res 2009;15(24):7684-92)},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/24/7684}
}
@ARTICLE{Sooriakumaran2009,
author = {Sooriakumaran, P. And Macanas-pirard, P. And Bucca, G. And Henderson,
A. And Langley, S.e.m. And Laing, R.w. And Smith, C.p. And Laing,
E.e. And Coley, H.m.},
title = {A Gene Expression Profiling Approach Assessing Celecoxib in a Randomized
Controlled Trial in Prostate Cancer},
journal = {Cancer Genomics Proteomics},
year = {2009},
volume = {6},
pages = {93--99},
number = {2},
month = mar,
abstract = {Background: We performed a pilot study, looking at the COX-2 inhibitor
celecoxib, on newly diagnosed prostate cancer patients in the neo-adjuvant
setting using DNA microarray analysis. Patients and Methods: This
was a single-blinded, randomized controlled phase II presurgical
(radical prostatectomy) 28-day trial of celecoxib versus no drug
in patients with localized T1-2 N0 M0 prostate cancer. cDNA microarray
analysis was carried out on prostate cancer biopsies taken from freshly
obtained radical prostatectomy samples. Results were confirmed by
qPCR analysis of a selection of genes. Results: Multiple genes were
differentially expressed in response to celecoxib treatment. Statistical
analysis of microarray data indicated 24 genes were up-regulated
and 4 genes down-regulated as a consequence of celecoxib treatment.
Gene changes e.g. survivin, SRP72kDa, were associated with promoting
apoptotic cell death, enhancement of antioxidant processes and tumour
suppressor function (p73 and cyclin B1 up-regulation). Conclusion:
Celecoxib at 400 mg b.i.d. for 4 weeks perioperatively gave rise
to changes in gene expression in prostate cancer tissue consistent
with enhancement of apoptosis and tumour suppressor function. Given
the short time interval for the duration of this study, the data
are encouraging and provide a good rationale for conducting further
trials of celecoxib in prostate cancer.},
url = {http://cgp.iiarjournals.org/cgi/content/abstract/6/2/93}
}
@ARTICLE{Soos2010,
author = {Soos, Vilmos and Sebestyen, Endre and Juhasz, Angela and Light, Marnie
and Kohout, Ladislav and Szalai, Gabriella and Tandori, Julia and
van Staden, Johannes and Balazs, Ervin},
title = {Transcriptome analysis of germinating maize kernels exposed to smoke-water
and the active compound KAR1},
journal = {BMC Plant Biology},
year = {2010},
volume = {10},
pages = {236},
number = {1},
abstract = {BACKGROUND:Smoke released from burning vegetation functions as an
important environmental signal promoting the germination of many
plant species following a fire. It not only promotes the germination
of species from fire-prone habitats, but several species from non-fire-prone
areas also respond, including some crops. The germination stimulatory
activity can largely be attributed to the presence of a highly active
butenolide compound, 3-methyl-2H-furo[2,3-c]pyran-2-one (referred
to as karrikin 1 or KAR1), that has previously been isolated from
plant-derived smoke. Several hypotheses have arisen regarding the
molecular background of smoke and KAR1 action. RESULTS:In this paper
we demonstrate that although smoke-water and butenolide treatment
of maize kernels result in a similar physiological response, the
gene expression and the protein ubiquitination patterns are quite
different. Treatment with smoke-water enhanced the ubiquitination
of proteins and activated protein-degradation-related genes. This
effect was completely absent from butenolide-treated kernels, in
which a specific aquaporin gene was distinctly upregulated. CONCLUSIONS:Our
findings indicate that the array of bioactive compounds present in
smoke-water form an environmental signal and may act together in
germination stimulation. It is highly possible that the smoke/butenolide
'signal' is perceived by a receptor that is shared with the signal
transduction system implied in perceiving environmental cues (especially
stresses and light), or some kind of specialized receptor exists
in fire-prone plant species which diverged from a more general one
present in a common ancestor, and also found in the non fire-prone
plants allowing for a somewhat weaker but still significant response.
Besides their obvious use in agricultural practices, smoke and butenolide
can be used in studies to gain further insight into the transcriptional
changes during germination.},
doi = {10.1186/1471-2229-10-236},
issn = {1471-2229},
pubmedid = {21044315},
url = {http://www.biomedcentral.com/1471-2229/10/236}
}
@ARTICLE{Sopher2004,
author = {Sopher, Bryce L and Thomas Jr., Patrick S and LaFevre-Bernt, Michelle
A and Holm, Ida E and Wilke, Scott A and Ware, Carol B and Jin, Lee-Way
and Libby, Randell T and Ellerby, Lisa M and La Spada, Albert R},
title = {Androgen Receptor YAC Transgenic Mice Recapitulate SBMA Motor Neuronopathy
and Implicate VEGF164 in the Motor Neuron Degeneration},
journal = {Neuron},
year = {2004},
volume = {41},
pages = {687--699},
number = {5},
month = mar,
abstract = {X-linked spinal and bulbar muscular atrophy (SBMA) is an inherited
neuromuscular disorder characterized by lower motor neuron degeneration.
SBMA is caused by polyglutamine repeat expansions in the androgen
receptor (AR). To determine the basis of AR polyglutamine neurotoxicity,
we introduced human AR yeast artificial chromosomes carrying either
20 or 100 CAGs into mouse embryonic stem cells. The AR100 transgenic
mice developed a late-onset, gradually progressive neuromuscular
phenotype accompanied by motor neuron degeneration, indicating striking
recapitulation of the human disease. We then tested the hypothesis
that polyglutamine-expanded AR interferes with CREB binding protein
(CBP)-mediated transcription of vascular endothelial growth factor
(VEGF) and observed altered CBP-AR binding and VEGF reduction in
AR100 mice. We found that mutant AR-induced death of motor neuron-like
cells could be rescued by VEGF. Our results suggest that SBMA motor
neuronopathy involves altered expression of VEGF, consistent with
a role for VEGF as a neurotrophic/survival factor in motor neuron
disease.},
issn = {0896-6273},
url = {http://www.sciencedirect.com/science/article/B6WSS-4BW0SV4-5/2/8274d4c9bc1ab9e09cebcfa7fb66af86}
}
@ARTICLE{SORBY2011,
author = {SORBY, LISE AAGAARD and KLEIVELAND, CHARLOTTE RAMSTAD and ANDERSEN,
SOLVEIG NORHEIM and BUKHOLM, IDA RASHIDA KHAN and JACOBSEN, MORTEN
BJ.},
title = {The Endothelin Axis in the Metastatic Process of Colon Carcinoma},
journal = {Anticancer Res},
year = {2011},
volume = {31},
pages = {861--869},
number = {3},
month = mar,
abstract = {Background: The endothelin axis has recently emerged as an important
factor in tumour metastasis. The aim of this study was to investigate
the endothelin axis and its downstream pathways related to metastasis
in colon carcinoma. Materials and Methods: mRNA expression of 36
genes associated with the endothelin axis in 18 non-metastatic and
20 metastatic colon carcinomas with individual-matched normal mucosa
were evaluated using real-time reverse transcription polymerase chain
reaction. Results: Seventeen out of 36 genes, including endothelin
A receptor, were significantly overexpressed in the tumour tissue
compared to the individual-matched normal mucosa. Seven out of 36
genes, including endothelin B receptor, were significantly down-regulated
in tumour tissue. Phosphatase and tensin homolog (PTEN) was significantly
down-regulated in the metastatic patients compared to the non-metastatic
patients. Conclusion: This study indicated that central genes in
the endothelin axis are overexpressed when colon tissue becomes malignant.
Down-regulation of PTEN may promote a progressive phenotype of colon
carcinomas.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/31/3/861}
}
@ARTICLE{Sormani2011,
author = {Sormani, R. and Delannoy, E. and Lageix, S. and Bitton, F. and Lanet,
E. and Saez-Vasquez, J. and Deragon, J. M. and Renou, J. P. and Robaglia,
C.},
title = {Sublethal Cadmium Intoxication In Arabidopsis thaliana Impacts Translation
at Multiple Levels},
journal = {Plant Cell Physiol.},
year = {2011},
volume = {52},
pages = {436--447},
number = {2},
month = feb,
abstract = {To study the impact of translational regulation during heavy metal
poisoning, Arabidopsis thaliana cell cultures were submitted to sublethal
cadmium stress. At the concentration used, cadmium had a minimal
impact on the growth of the culture but induced an accumulation of
high molecular weight polysomes without de novo production of new
ribosomes together with a reduction of protein synthesis. In addition,
cadmium stress induces phosphorylation of eukaryotic initiation factor
2{alpha} by GCN2 and, in planta, gcn2 mutants are more sensitive
to cadmium stress, suggesting a role for this translational regulation
mechanism in the response to cadmium stress. Microarray analysis
of total and polysomal RNAs in control and cadmium-treated cells
reveals a large class of genes for which a variation in total RNA
abundance is not linked to a variation in polysomal loading, suggesting
that transcription and translation are uncoupled and that these genes
are not recruited at the initiation step of translation.},
comment = {10.1093/pcp/pcr001},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/52/2/436}
}
@ARTICLE{Sorsa2007,
author = {Sorsa, Liisa Johanna and Feldmann, Friederike and Hildinger, Kirsten
and Dufke, Severin and Schubert, Sören},
title = {Characterization of four novel genomic regions of uropathogenic Escherichia
coli highly associated with the extraintestinal virulent phenotype:
A jigsaw puzzle of genetic modules},
journal = {International Journal of Medical Microbiology},
year = {2007},
volume = {297},
pages = {83--95},
number = {2},
month = apr,
abstract = {Extraintestinal pathogenic Escherichia coli (ExPEC) are a major cause
of urinary tract infections, sepsis, and neonatal meningitis. A variety
of virulence factors in these strains is encoded by mobile genetic
elements, such as transposons or pathogenicity islands (PAIs). Using
subtractive cloning of ExPEC genomes, we recently detected short
DNA fragments, which were significantly associated with the extraintestinal
virulent phenotype. In this study, we identified four novel genomic
DNA regions of the highly virulent uropathogenic E. coli strain JS299
carrying these previously identified DNA fragments. Characterization
of the partial sequences of the genomic DNA regions revealed complex
DNA arrangements with variable genetic compositions regarding the
G+C contents and codon usage patterns. The prevalence of 15 previously
uncharacterized genes was determined in a collection of clinical
ExPECs and commensal E. coli strains by means of DNA microarray analyses.
From this, 13 novel DNA sequences were demonstrated to be significantly
associated with extraintestinal virulent strains, and thus may represent
new virulence traits. Beside genes predicted to play a role in metabolic
functions, such as sucrose utilization (scr), we identified DNA sequences
shared by both ExPEC and enteropathogenic E. coli (EPEC). These sequences
were significantly more prevalent among ExPECs when compared to commensal
E. coli isolates. Our results support the idea of a considerable
genetic variability among ExPEC strains and suggest that the novel
genomic determinants described in this study may contribute to the
ExPEC virulence.},
issn = {1438-4221},
keywords = {Genomic variation, Virulence determinant, Extraintestinal pathogenic
Escherichia coli, DNA microarray},
url = {http://www.sciencedirect.com/science/article/B7GW0-4N08X7Y-1/2/4c3fc1af9a917024f489d5cc5eb29748}
}
@ARTICLE{Sorwell2011,
author = {Krystina G. Sorwell and Steven G. Kohama and Henryk F. Urbanski},
title = {Perimenopausal regulation of steroidogenesis in the nonhuman primate},
journal = {Neurobiology of Aging},
year = {2011},
pages = { - },
number = {0},
abstract = {Human aging is characterized by a marked decrease in circulating levels
of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), hormonal
changes associated with cognitive decline. Despite beneficial effects
of DHEA supplementation in rodents, studies in elderly humans have
generally failed to show cognitive improvement after treatment. In
the present study we evaluate the effects of age and estradiol supplementation
on expression of genes involved in the de novo synthesis of DHEA
and its conversion to estradiol in the rhesus macaque hippocampus.
Using reverse transcription polymerase chain reaction (RT-PCR) we
demonstrate the expression of genes associated with this synthesis
in several areas of the rhesus brain. Furthermore, real-time PCR
reveals an age-related attenuation of hippocampal expression level
of the genes CYP17A1, STS, and 3BHSD1/2. Additionally, short-term
administration of estradiol is associated with decreased expression
of CYP17A1, STS, SULT2B1, and AROMATASE, consistent with a downregulation
not only of estrogen synthesis from circulating DHEA, but also of
de novo DHEA synthesis within the hippocampus. These findings suggest
a decline in neurosteroidogenesis may account for the inefficacy
of DHEA supplementation in elderly humans, and that central steroidogenesis
may be a function of circulating hormones and menopausal status.},
doi = {10.1016/j.neurobiolaging.2011.05.004},
issn = {0197-4580},
keywords = {Aging},
url = {http://www.sciencedirect.com/science/article/pii/S0197458011001710}
}
@ARTICLE{Sosniyenko2010,
author = {Sosniyenko, Serhiy and Parkanova, Daniela and Illnerova, Helena and
Sladek, Martin and Sumova, Alena},
title = {Different mechanisms of adjustment to a change of the photoperiod
in the suprachiasmatic and liver circadian clocks},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2010},
volume = {298},
pages = {R959--971},
number = {4},
month = apr,
abstract = {Changes in photoperiod modulate the circadian system, affecting the
function of the central clock located in the suprachiasmatic nucleus
(SCN) of the hypothalamus. The aim of the present study was to elucidate
the dynamics of adjustment to a change of a long photoperiod with
18 h of light to a short photoperiod with 6 h of light of clock gene
expression rhythms in the mouse SCN and in the peripheral clock in
the liver, as well as of the locomotor activity rhythm. Three, five,
and thirteen days after the photoperiod change, daily profiles of
Per1, Per2, and Rev-erb{alpha} expression in the rostral, middle,
and caudal parts of the SCN and of Per2 and Rev-erb{alpha} in the
liver were determined by in situ hybridization and real-time RT-PCR,
respectively. The clock gene expression rhythms in the different
SCN regions, desynchronized under the long photoperiod, attained
synchrony gradually following the transition from long to short days,
mostly via advancing the expression decline. The photoperiodic modulation
of the SCN was due not only to the degree of synchrony among the
SCN regions but also to different waveforms of the rhythms in the
individual SCN parts. The locomotor activity rhythm adjusted gradually
to short days by advancing the activity onset, and the liver rhythms
adjusted by advancing the Rev-erb{alpha} expression rise and Per2
decline. These data indicate different mechanisms of adjustment to
a change of the photoperiod in the central SCN clock and the peripheral
liver clock.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/298/4/R959}
}
@ARTICLE{Sosnoski2007,
author = {Sosnoski, Donna M. and Gay, Carol V.},
title = {Evaluation of bone-derived and marrow-derived vascular endothelial
cells by microarray analysis},
journal = {J. Cell. Biochem.},
year = {2007},
volume = {102},
pages = {463--472},
number = {2},
abstract = {Abstract 10.1002/jcb.21307.abs This study focused on the differential
expression levels of proteins that may exist between bone-derived
and marrow-derived vascular endothelial cells (BVEC and MVEC). The
vascular cells were isolated from trabecular bone regions and central
marrow cavity regions of mouse long bones. Cells were cultured for
1 week to expand the population then separated from non-vascular
cells using biotinylated isolectin B4, streptavidin-coated metallic
microbeads, and a magnetic column. After an additional week of culture
time, RNA was isolated from both cell types and compared using microarray
analysis. RT-PCR was used to confirm and relatively quantitate the
RNA messages. The bone-derived cells expressed more aldehyde dehydrogenase
3A1 (ALDH3A1), Secreted Modular Calcium-2 (SMOC-2), CCAAT enhancer
binding protein (C/EBP-β), matrix metalloproteinase 13 (MMP-13),
and annexin 8 (ANX8) than the marrow-derived cells. Spα and matrix
GLA-protein (MGP) were produced in greater abundance by the marrow-derived
cells. This study reveals that there are profound and unique differences
between the vasculature of the metaphysis as compared to that of
the central marrow cavity. The unique array of proteins expressed
by the bone-derived endothelial cells may support growth of tumors
from cancer cells that frequently metastasize and lodge in the trabecular
bone regions. J. Cell. Biochem. 102: 463–472, 2007. © 2007 Wiley-Liss,
Inc.},
issn = {1097-4644},
keywords = {vascular endothelial cells, bone vasculature, microarray},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.21307}
}
@ARTICLE{Sotelo2010,
author = {Sotelo, Jose and Esposito, Dominic and Duhagon, Maria Ana and Banfield,
Kelley and Mehalko, Jennifer and Liao, Hongling and Stephens, Robert
M. and Harris, Timothy J. R. and Munroe, David J. and Wu, Xiaolin},
title = {Long-range enhancers on 8q24 regulate c-Myc},
journal = {PNAS},
year = {2010},
volume = {107},
pages = {3001--3005},
number = {7},
month = feb,
abstract = {Recent genomewide association studies have found multiple genetic
variants on chromosome 8q24 that are significantly associated with
an increased susceptibility to prostate, colorectal, and breast cancer.
These risk loci are located in a "gene desert," a few hundred kilobases
telomeric to the Myc gene. To date, the biological mechanism(s) underlying
these associations remain unclear. It has been speculated that these
8q24 genetic variant(s) might affect Myc expression by altering its
regulation or amplification status. Here, we show that multiple enhancer
elements are present within this region and that they can regulate
transcription of Myc. We also demonstrate that one such enhancer
element physically interacts with the Myc promoter via transcription
factor Tcf-4 binding and acts in an allele specific manner to regulate
Myc expression.},
url = {http://www.pnas.org/cgi/content/abstract/107/7/3001}
}
@ARTICLE{Sotiriou2006,
author = {Sotiriou, Christos and Wirapati, Pratyaksha and Loi, Sherene and
Harris, Adrian and Fox, Steve and Smeds, Johanna and Nordgren, Hans
and Farmer, Pierre and Praz, Viviane and Haibe-Kains, Benjamin and
Desmedt, Christine and Larsimont, Denis and Cardoso, Fatima and Peterse,
Hans and Nuyten, Dimitry and Buyse, Marc and Van de Vijver, Marc
J. and Bergh, Jonas and Piccart, Martine and Delorenzi, Mauro},
title = {Gene Expression Profiling in Breast Cancer: Understanding the Molecular
Basis of Histologic Grade To Improve Prognosis},
journal = {J Natl Cancer Inst},
year = {2006},
volume = {98},
pages = {262--272},
number = {4},
month = feb,
abstract = {Background: Histologic grade in breast cancer provides clinically
important prognostic information. However, 30%-60% of tumors are
classified as histologic grade 2. This grade is associated with an
intermediate risk of recurrence and is thus not informative for clinical
decision making. We examined whether histologic grade was associated
with gene expression profiles of breast cancers and whether such
profiles could be used to improve histologic grading. Methods: We
analyzed microarray data from 189 invasive breast carcinomas and
from three published gene expression datasets from breast carcinomas.
We identified differentially expressed genes in a training set of
64 estrogen receptor (ER)-positive tumor samples by comparing expression
profiles between histologic grade 3 tumors and histologic grade 1
tumors and used the expression of these genes to define the gene
expression grade index. Data from 597 independent tumors were used
to evaluate the association between relapse-free survival and the
gene expression grade index in a Kaplan-Meier analysis. All statistical
tests were two-sided. Results: We identified 97 genes in our training
set that were associated with histologic grade; most of these genes
were involved in cell cycle regulation and proliferation. In validation
datasets, the gene expression grade index was strongly associated
with histologic grade 1 and 3 status; however, among histologic grade
2 tumors, the index spanned the values for histologic grade 1-3 tumors.
Among patients with histologic grade 2 tumors, a high gene expression
grade index was associated with a higher risk of recurrence than
a low gene expression grade index (hazard ratio = 3.61, 95% confidence
interval = 2.25 to 5.78; P<.001, log-rank test). Conclusions: Gene
expression grade index appeared to reclassify patients with histologic
grade 2 tumors into two groups with high versus low risks of recurrence.
This approach may improve the accuracy of tumor grading and thus
its prognostic value.},
url = {http://jnci.oxfordjournals.org/cgi/content/abstract/98/4/262}
}
@ARTICLE{Soto-Pantoja2009,
author = {Soto-Pantoja, David R. and Menon, Jyotsana and Gallagher, Patricia
E. and Tallant, E. Ann},
title = {Angiotensin-(1-7) inhibits tumor angiogenesis in human lung cancer
xenografts with a reduction in vascular endothelial growth factor},
journal = {Mol. Cancer Ther.},
year = {2009},
volume = {8},
pages = {1676--1683},
number = {6},
month = jun,
abstract = {Angiotensin-(1-7) [Ang-(1-7)] is an endogenous seven-amino acid peptide
hormone with antiproliferative properties. Our previous studies showed
that Ang-(1-7) inhibits the growth of human lung cancer cells in
vitro and reduces the size of human lung tumor xenografts in vivo.
In the current study, s.c. injection of Ang-(1-7) not only caused
a significant reduction in human A549 lung tumor growth but also
markedly decreased vessel density, suggesting that the heptapeptide
inhibits angiogenesis to reduce tumor size. A decrease in human endothelial
cell tubule formation in Matrigel was observed following a 16 h incubation
with Ang-(1-7), with a maximal reduction at a 10 nmol/L concentration.
Ang-(1-7) had similar antiangiogenic effects in the chick chorioallantoic
membrane, causing a >50% decrease in neovascularization. The Ang-(1-7)-induced
reduction in both endothelial cell tubule formation and vessel formation
in the chick was completely blocked by the specific Ang-(1-7) receptor
antagonist [D-proline7]-Ang-(1-7), suggesting that these biological
actions are mediated by an AT(1-7) receptor. Ang-(1-7) significantly
reduced vascular endothelial growth factor-A protein and mRNA in
tumors from mice treated with the heptapeptide compared with saline
controls as well as in the parent A549 human lung cancer cells in
culture. These results suggest that Ang-(1-7) may attenuate tumor
angiogenesis by reducing vascular endothelial growth factor-A, a
primary proangiogenic protein. Taken together, this study shows that
Ang-(1-7) exhibits significant antiangiogenic activity and may be
a novel therapeutic agent for lung cancer treatment targeting a specific
AT(1-7) receptor. [Mol Cancer Ther 2009;8(6):1676-83]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/8/6/1676}
}
@ARTICLE{Sotoca2011,
author = {Sotoca, Ana M. and Sollewijn Gelpke, Maarten D. and Boeren, Sjef
and Strom, Anders and Gustafsson, Jan-Ake and Murk, Albertinka J.
and Rietjens, Ivonne M. C. M. and Vervoort, Jacques},
title = {Quantitative Proteomics and Transcriptomics Addressing the Estrogen
Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed
to the Phytoestrogen Genistein},
journal = {Mol. Cell. Proteomics},
year = {2011},
volume = {10},
pages = {M110.002170--},
number = {1},
month = jan,
abstract = {The present study addresses, by transcriptomics and quantitative stable
isotope labeling by amino acids in cell culture (SILAC)-based proteomics,
the estrogen receptor {alpha} (ER{alpha}) and {beta} (ER{beta})-mediated
effects on gene and protein expression in T47D breast cancer cells
exposed to the phytoestrogen genistein. Using the T47D human breast
cancer cell line with tetracycline-dependent ER{beta} expression
(T47D-ER{beta}), the effect of a varying intracellular ER{alpha}/ER{beta}
ratio on genistein-induced gene and protein expression was characterized.
Results obtained reveal that in ER{alpha}-expressing T47D-ER{beta}
cells with inhibited ER{beta} expression genistein induces transcriptomics
and proteomics signatures pointing at rapid cell growth and migration
by dynamic activation of cytoskeleton remodeling. The data reveal
an interplay between integrins, focal adhesion kinase, CDC42, and
actin cytoskeleton signaling cascades, occurring upon genistein treatment,
in the T47D-ER{beta} breast cancer cells with low levels of ER{alpha}
and no expression of ER{beta}. In addition, data from our study indicate
that ER{beta}-mediated gene and protein expression counteracts ER{alpha}-mediated
effects because in T47D-ER{beta} cells expressing ER{beta} and exposed
to genistein transcriptomics and proteomics signatures pointing at
a clear down-regulation of cell growth and induction of cell cycle
arrest and apoptosis were demonstrated. These results suggest that
ER{beta} decreases cell motility and metastatic potential as well
as cell survival of the breast cancer cell line. It is concluded
that the effects of genistein on proteomics and transcriptomics end
points in the T47D-ER{beta} cell model are comparable with those
reported previously for estradiol with the ultimate estrogenic effect
being dependent on the relative affinity for both receptors and on
the receptor phenotype (ER{alpha}/ER{beta} ratio) in the cells or
tissue of interest.},
comment = {10.1074/mcp.M110.002170},
url = {http://www.mcponline.org/cgi/content/abstract/10/1/M110.002170}
}
@ARTICLE{Soualhine2005,
author = {Soualhine, Hafid and Brochu, Vicky and Ménard, François and Papadopoulou,
Barbara and Weiss, Karl and Bergeron, Michel G. and Légaré, Danielle
and Drummelsmith, Jolyne and Ouellette, Marc},
title = {A proteomic analysis of penicillin resistance in Streptococcus pneumoniae
reveals a novel role for PstS, a subunit of the phosphate ABC transporter},
journal = {Molecular Microbiology},
year = {2005},
volume = {58},
pages = {1430--1440},
number = {5},
abstract = {Summary Resistance to penicillin is widespread in the Gram-positive
bacterium Streptococcus pneumoniae, and while several mutations are
known to be implicated in resistance other mechanisms are likely
to occur. We used a proteomic screen of two independent mutants in
which resistance was selected in vitro. We found a number of differentially
expressed proteins including PstS, a subunit of the phosphate ABC
transporter of S. pneumoniae. This protein was increased in both
mutants, a phenotype correlated to increased RNA expression of the
entire phosphate ABC transporter operon. Inactivation of the pstS
gene led to increased susceptibility to penicillin in the wild-type
strain. To further link the expression of the ABC phosphate transporter
with penicillin resistance, we looked at pstS mRNA levels in 12 independent
clinical isolates sensitive and resistant to penicillin and found
an excellent correlation between resistance and increased expression
of pstS. Inactivation of pstS in one of the clinical isolates significantly
reduced penicillin resistance. Global approaches are ideally suited
for the discovery of novel factors in the biology of resistance.},
issn = {1365-2958},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2005.04914.x}
}
@ARTICLE{Soubeyran2011,
author = {Soubeyran, Isabelle and Mahouche, Isabelle and Grigoletto, Aude and
Leste-Lasserre, Thierry and Drutel, Guillaume and Rey, Christophe
and Pedeboscq, Stephane and Blanchard, France and Brouste, Veronique
and Sabourin, Jean-Christophe and Bécouarn, Yves and Reiffers, Josy
and Ichas, François and De Giorgi, Francesca},
title = {Tissue Microarray Cytometry Reveals Positive Impact of Homeodomain
Interacting Protein Kinase 2 in Colon Cancer Survival Irrespective
of p53 Function},
journal = {The American Journal of Pathology},
year = {2011},
volume = {178},
pages = {1986--1998},
number = {5},
month = may,
abstract = {The human p53 gene is a tumor suppressor mutated in half of colon
cancers. Although p53 function appears important for proliferation
arrest and apoptosis induced by cancer therapeutics, the prognostic
significance of p53 mutations remains elusive. This suggests that
p53 function is modulated at a posttranslational level and that dysfunctions
affecting its modulators can have a prognostic impact. Among p53
modulators, homeodomain interacting protein kinase (HIPK) 2 emerges
as a candidate "switch" governing p53 transition from a cytostatic
to a proapoptotic function. Thus, we investigated the possible prognostic
role of HIPK2 on a retrospective series of 80 colon cancer cases
by setting up a multiplexed cytometric approach capable of exploring
correlative protein expression at the single tumor cell level on
TMA. Crossing the data with quantitative PCR and p53 gene sequencing
and p53 functional assays, we observed the following: despite a strong
impact on p21 transcription, the presence of disabling p53 mutations
has no prognostic value, and the increased expression of the HIPK2
protein in tumor cells compared with paired normal tissue cells has
a strong impact on survival. Unexpectedly, HIPK2 effect does not
appear to be mediated by p53 function because it is also observed
in p53-disabling mutated backgrounds. Thus, our results point to
a prominent and p53-independent role of HIPK2 in colon cancer survival.},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011001301}
}
@ARTICLE{Souda2009,
author = {Souda, Masakazu and Umekita, Yoshihisa and Abeyama, Kazuhiro and
Yoshida, Hiroki},
title = {Gene expression profiling during rat mammary carcinogenesis induced
by 7,12-dimethylbenz[a]anthracene},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {1285--1297},
number = {6},
abstract = {Abstract 10.1002/ijc.24396.abs 7,12-Dimethylbenz[a]anthracene (DMBA)-induced
rat mammary carcinoma is a well-recognized model; however, the genetic
alterations during its carcinogenesis have yet to be determined.
We used laser capture microdissection to specifically isolate cells
from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks
after sesame oil treatment (control) or DMBA treatment (DMBA-TEBs),
ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC).
Using an oligonucleotide microarray representing 20,600 rat probe
sequences, we analyzed gene expression profiles and validated mRNA
and protein levels of genes of interest byreal-time quantitative
PCR and immunohistochemistry. The number of differentially expressed
genes dramatically increased from DMBA-TEBs (63) to DCIS (798) and
MC (981). Only the expression of PEP-19, an anti-apoptotic gene,
showed significant increases in DMBA-TEBs (4-fold), DCIS (10-fold)
and MC (16-fold). MMP-13 expression was increased markedly in DCIS
(19-fold) and MC (61-fold) while OPN expression was increased 6-fold
in DCIS and 8-fold in MC. MMP-7 expression was increased 4-fold in
MC. Nidogen-1; a participant in the assembly of basement membranes,
TSP-2; an inhibitor of angiogenesis and COUP-TFI; a transcription
repressor showed significant decreases in DCIS (4-, 9- and 17-fold,
respectively) and MC (10-, 37- and 100-fold). Network analyses with
IPA software revealed that the most significant network included
Akt groups in DCIS and ERK groups in MC. The present findings provide
us with a better understanding of the molecular alteration that occur
during mammary carcinogenesis and suggest the importance of PEP-19
overexpression in the very early stage of mammary carcinogenesis.
© 2009 UICC},
issn = {1097-0215},
keywords = {mammary carcinoma, microarray, laser microdissection, 7,12-dimethylbenz[a]anthracene,
terminal end buds, ductal carcinoma in situ},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24396}
}
@ARTICLE{Soule2009,
author = {Soule, Tanya and Garcia-Pichel, Ferran and Stout, Valerie},
title = {Gene Expression Patterns Associated with the Biosynthesis of the
Sunscreen Scytonemin in Nostoc punctiforme ATCC 29133 in Response
to UVA Radiation},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {4639--4646},
number = {14},
month = jul,
abstract = {Under exposure to UV radiation, some cyanobacteria synthesize sunscreen
compounds. Scytonemin is a heterocyclic indole-alkaloid sunscreen,
the synthesis of which is induced upon exposure to UVA (long-wavelength
UV) radiation. We previously identified and characterized an 18-gene
cluster associated with scytonemin biosynthesis in the cyanobacterium
Nostoc punctiforme ATCC 29133; we now report on the expression response
of these genes to a step-up shift in UVA exposure. Using quantitative
PCR on cDNAs from the N. punctiforme transcriptome and primers targeting
each of the 18 genes in the cluster, we followed their differential
expression in parallel subcultures incubated with and without UVA.
All 18 genes are induced by UVA irradiation, with relative transcription
levels that generally peak after 48 h of continuous UVA exposure.
A five-gene cluster implicated in the process of scytonemin biosynthesis
solely on the basis of comparative genomics was also upregulated.
Furthermore, we demonstrate that all of the genes in the18-gene region
are cotranscribed as part of a single transcriptional unit.},
url = {http://jb.asm.org/cgi/content/abstract/191/14/4639}
}
@ARTICLE{SousaAbreu2009,
author = {de Sousa Abreu, Raquel and Sanchez-Diaz, Patricia C. and Vogel, Christine
and Burns, Suzanne C. and Ko, Daijin and Burton, Tarea L. and Vo,
Dat T. and Chennasamudaram, Soudhamini and Le, Shu-Yun and Shapiro,
Bruce A. and Penalva, Luiz O. F.},
title = {Genomic Analyses of Musashi1 Downstream Targets Show a Strong Association
with Cancer-related Processes},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {12125--12135},
number = {18},
month = may,
abstract = {Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal
functions in stem cell maintenance, nervous system development, and
tumorigenesis. Despite its importance, only three direct mRNA targets
have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has
been shown to affect their translation by binding to short elements
located in the 3'-untranslated region. To better understand Msi1
functions, we initially performed an RIP-Chip analysis in HEK293T
cells; this method consists of isolation of specific RNA-protein
complexes followed by identification of the RNA component via microarrays.
A group of 64 mRNAs was found to be enriched in the Msi1-associated
population compared with controls. These genes belong to two main
functional categories pertinent to tumorigenesis: 1) cell cycle,
cell proliferation, cell differentiation, and apoptosis and 2) protein
modification (including ubiquitination and ubiquitin cycle). To corroborate
our findings, we examined the impact of Msi1 expression on both mRNA
(transcriptomic) and protein (proteomic) expression levels. Genes
whose mRNA levels were affected by Msi1 expression have a Gene Ontology
distribution similar to RIP-Chip results, reinforcing Msi1 participation
in cancer-related processes. The proteomics study revealed that Msi1
can have either positive or negative effects on gene expression of
its direct targets. In summary, our results indicate that Msi1 affects
a network of genes and could function as a master regulator during
development and tumor formation.},
url = {http://www.jbc.org/cgi/content/abstract/284/18/12125}
}
@ARTICLE{Sousa2010,
author = {Sousa, Silvia A. and Ramos, Christian G. and Moreira, Leonilde M.
and Leitao, Jorge H.},
title = {The hfq gene is required for stress resistance and full virulence
of Burkholderia cepacia to the nematode Caenorhabditis elegans},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {896--908},
number = {3},
month = mar,
abstract = {The Burkholderia cepacia complex (Bcc) emerged as problematic opportunistic
pathogens to cystic fibrosis (CF) patients. Although several virulence
factors have been identified in Bcc, the knowledge of their relative
contribution to Bcc pathogenicity remains scarce. In this work, we
describe the identification and characterization of a B. cepacia
IST408 mutant containing a disruption in the hfq gene. In other bacteria,
Hfq is a global regulator of metabolism, acting as an RNA chaperone
involved in the riboregulation of target mRNAs by small regulatory
non-coding RNAs (sRNAs). The B. cepacia Hfq protein was overproduced
as a histidine-tagged derivative, and we show evidence that the protein
forms hexamers and binds sRNAs. When provided in trans, the B. cepacia
IST408 hfq gene complemented the Escherichia coli hfq mutant strain
GS081. Our results also show that the B. cepacia hfq mutant is more
susceptible to stress conditions mimicking those faced by Bcc bacteria
when infecting the CF host. In addition, the B. cepacia hfq mutant
and two hfq mutants derived from B. dolosa and B. ambifaria clinical
isolates also exhibited a reduced ability to colonize and kill the
nematode Caenorhabditis elegans, used as an infection model. These
data, together with the conservation of Hfq orthologues among Bcc,
strongly suggest that Hfq plays a major role in the survival of Bcc
under stress conditions, contributing to the success of Bcc as CF
pathogens.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/3/896}
}
@ARTICLE{Southern2006,
author = {Southern, Paul B. and Argonza-Barrett, Rhodora H. and Lewis, Fraser
and Love, William and Sharma-Oates, Archana and Bailey, Jerome and
Quirke, Philip},
title = {RNA gene expression signatures and DNA copy number changes in hepatocellular
carcinoma formalin-fixed paraffin-embedded archived samples compared
to fresh and normal tissues from the same patients},
journal = {AACR Meeting Abstracts},
year = {2006},
volume = {2006},
pages = {40--},
number = {1},
month = apr,
abstract = {About 17,500 new cases of primary liver cancer are diagnosed every
year in the United States; twice the number for men as in women.
According to the American Cancer Society, 15,420 people will die
of liver cancer in the US for 2005. In the developing countries of
Africa and East Asia, it is the most common type of cancer with higher
occurrences than in the US per year. Despite improvements made in
the treatment and therapy for liver cancer over the years, many patients
still undergo expensive chemotherapy even though their particular
cancer is resistant to such treatment. The side-effects are devastating
without having any benefit to the patient. Using formalin-fixed Paraffin-embedded
(FFPE) samples, patient outcomes can be linked to the changes seen
in the DNA and the RNA levels from these archived tissues. We have
used paraffin-embedded tissue human hepatocellular carcinoma (HCC)
and cirrhosis to produce RNA and DNA of sufficient quantity and quality
to yield distinct genetic signatures specific to HCC and liver cirrhosis
when hybridized to the whole transcriptome (RNA) and whole genome
(DNA) Agilent microarrays. The gene expression signatures and copy
number changes were highly correlated for fresh tumor samples from
the same biopsy with the archived material. Normal liver samples
from the peripheral sites of the biopsy, as determined by histology
and FISH, were similarly obtained as both frozen and paraffin-embedded
material. DNA and RNA were similarly extracted and used on the microarrays.
For RNA, an HCC-specific genetic expression signature was seen consisting
of a candidate gene set. The 2,530 candidate genes represent features
whose differential expression is both significant (>2 fold change)
and conserved across both fresh and FFPE sources of RNA. Most of
the DNA copy number changes seen are de novo and specific to the
HCC tumors, both fresh and FFPE, but are not present in either fresh
or FFPE normal specimen. For FFPE extractions, only 73% of the specimen
extracted yielded the quality and quantity required by whole genome
and whole transcriptome microarray analysis. Quality measurements
with UV spectrophotometer and with the Agilent 2100 Bioanalyzer correctly
predicted the successful hybridizations. This combined DNA and RNA
analyses show the powerful potential in using archived samples for
a retrospective study in cancer regimes. By analyzing FFPE DNA, it
may help determine why some patients respond and others are resistant
to treatments. Analysis of tumor DNA, together with RNA gene expression
alterations, may aid in predicting which immunotherapy and chemotherapy
would be of the highest benefit to the individual patients.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/40}
}
@ARTICLE{Soverchia2006,
author = {Soverchia, L. and Mosconi, G. and Ruggeri, B. and Ballarini, P. and
Catone, G. and Degl'Innocenti, S. and Nabissi, M. and Polzonetti-Magni,
A.M.},
title = {Proopiomelanocortin gene expression and β-endorphin localization
in the pituitary, testis, and epididymis of stallion},
journal = {Mol. Reprod. Dev.},
year = {2006},
volume = {73},
pages = {1--8},
number = {1},
abstract = {Abstract 10.1002/mrd.20341.abs Proopiomelanocortin (POMC) is a precursor
protein that contains the sequences of several bioactive peptides
including adrenocorticotropin (ACTH), β-endorphin (β-EP), and melanocyte-stimulating-hormone
(MSH). POMC is synthesized in the pituitary gland, brain, and many
peripheral tissues. Immunoreactive POMC-derived peptides as well
as POMC-like mRNA have been evidenced in several nonpituitary tissues,
thus suggesting that POMC is actively synthesized by these tissues.
The present study was aimed at evaluating if also in the case of
stallion POMC-derived peptide, β-EP, is produced locally in the
testis, thus playing effects in a paracrine/autocrine fashion. To
investigate this hypothesis the POMC gene expression was analyzed
using 3′ RACE-PCR and Northern Blot approaches in the testis and
epididimys of stallion; moreover, immunocytochemical localization
for β-EP was also performed through confocal laser microscopy. The
immunofluorescence results showed a positive β-EP reaction not only
in cellular nest of pituitary but also in the testis and genital
tract of stallion, which function could be related with sperm mobility.
Such role seem not to be no dependent on the peptide synthesized
locally, because the molecular biology approach demonstrated the
presence of POMC transcript in the pituitary only. In fact the Northern
Blot analysis showed the presence of a single POMC transcript in
the pituitary while no signal was detected in the testis and epididimys.
The same results were obtained by applied 3′ RACE-PCR analysis.
In conclusion, opioid-derived peptide β-EP is present in the genital
tract of stallion, but is not locally produced as in other mammalian,
and nonmammalian models; its possible biological function at testicular
level could be linked to a long-loop feed-back mechanisms. Mol. Reprod.
Dev. © 2005 Wiley-Liss, Inc.},
issn = {1098-2795},
keywords = {stallion, POMC mRNA, β-endorphin, pituitary, testis, epididymis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mrd.20341}
}
@ARTICLE{Soyfoo2007,
author = {Soyfoo, Muhammad S. and De Vriese, Carine and Debaix, Huguette and
Martin-Martinez, Maria D. and Mathieu, Chantal and Devuyst, Olivier
and Steinfeld, Serge D. and Delporte, Christine},
title = {Modified aquaporin 5 expression and distribution in submandibular
glands from NOD mice displaying autoimmune exocrinopathy},
journal = {Arthritis \& Rheumatism},
year = {2007},
volume = {56},
pages = {2566--2574},
number = {8},
abstract = {Abstract 10.1002/art.22826.abs Objective To investigate the expression
and localization of aquaporin 5 (AQP5) in salivary glands and salivary
gland function in the NOD mouse. Methods All experiments were performed
using NOD and BALB/c mice (ages 8 weeks and 24 weeks). Real-time
reverse transcription–polymerase chain reaction, Western blotting,
and immunohistochemical analysis were used to study the expression
and distribution of AQP5 in salivary glands. In addition, salivary
gland function was determined. Results Compared with the levels in
BALB/c mice, relative AQP5 messenger RNA levels were not significantly
modified in the parotid glands from NOD mice of both ages but were
significantly increased in the submandibular glands from NOD mice
of both ages. Western blot analyses of both salivary gland membranes
revealed that the level of AQP5 protein was increased in 24-week-old
NOD mice. Important inflammatory infiltrates were observed in the
submandibular glands, but not in the parotid glands, from 24-week-old
NOD mice. The 8-week-old and 24-week-old BALB/c mice and the 8-week-old
NOD mice showed AQP5 primarily at the apical membrane of the salivary
gland acinus. In contrast, in acini from the submandibular glands
(but not the parotid glands) from 24-week-old NOD mice, AQP5 staining
was reduced at the apical membrane but was increased at the basal
membrane. A moderately statistically significant decrease in pilocarpine-stimulated
salivary flow was observed in 24-week-old NOD mice compared with
that in age-matched BALB/c mice. Conclusion Submandibular glands
from 24-week-old NOD mice displayed inflammatory infiltrates, increased
AQP5 protein expression, and impaired AQP5 distribution. However,
the moderately statistically significant decrease in the salivary
flow rate in these mice did not match the extent of AQP5 misdistribution.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.22826}
}
@ARTICLE{Spade2011,
author = {Spade, Daniel J. and Knoebl, Iris and Denslow, Nancy D.},
title = {Cesium chloride gradient centrifugation improves the quality of total
RNA preparations from the gastropod Strombus gigas and the coral
Montastraea faveolata},
journal = {Journal of Experimental Marine Biology and Ecology},
year = {2011},
volume = {402},
pages = {43--48},
number = {1-2},
month = jun,
abstract = {RNA preparation from marine invertebrate samples including gastropods
and cnidarians is often difficult, producing low-purity RNA samples
that perform poorly in downstream procedures. This is increasingly
problematic given the current interest in transcriptional studies
of marine invertebrates. We report an RNA preparation method using
a phenol/chloroform extraction followed by CsCl gradient centrifugation,
modified from previous reports and adapted for a modern benchtop
ultracentrifuge. This method produced improved spectrophotometric
indicators of RNA quality (A260/A280 and A260/A230) for Strombus
gigas Linnaeus, 1758, testis samples and improved RNA integrity number
(RIN) for Montastraea faveolata Ellis, 1786, samples, relative to
a preparation procedure that relies solely on chemical extraction
of RNA. Rate of success in microarray labeling reactions was slightly,
but not significantly, improved following CsCl gradient centrifugation.
A real-time RT-PCR assay performed using CsCl-prepared samples was
efficient (92.5%) and produced consistent and reproducible results.},
issn = {0022-0981},
keywords = {Cnidaria, Corals, Gastropods, Methods, Mollusca, RNA preparation},
url = {http://www.sciencedirect.com/science/article/pii/S0022098111001274}
}
@ARTICLE{Spade2011a,
author = {Daniel J. Spade and Iris Knoebl and Nancy D. Denslow},
title = {Cesium chloride gradient centrifugation improves the quality of total
RNA preparations from the gastropod Strombus gigas and the coral
Montastraea faveolata},
journal = {Journal of Experimental Marine Biology and Ecology},
year = {2011},
volume = {402},
pages = {43 - 48},
number = {1–2},
abstract = {RNA preparation from marine invertebrate samples including gastropods
and cnidarians is often difficult, producing low-purity RNA samples
that perform poorly in downstream procedures. This is increasingly
problematic given the current interest in transcriptional studies
of marine invertebrates. We report an RNA preparation method using
a phenol/chloroform extraction followed by CsCl gradient centrifugation,
modified from previous reports and adapted for a modern benchtop
ultracentrifuge. This method produced improved spectrophotometric
indicators of RNA quality (A260/A280 and A260/A230) for Strombus
gigas Linnaeus, 1758, testis samples and improved RNA integrity number
(RIN) for Montastraea faveolata Ellis, 1786, samples, relative to
a preparation procedure that relies solely on chemical extraction
of RNA. Rate of success in microarray labeling reactions was slightly,
but not significantly, improved following CsCl gradient centrifugation.
A real-time RT-PCR assay performed using CsCl-prepared samples was
efficient (92.5%) and produced consistent and reproducible results.},
doi = {10.1016/j.jembe.2011.03.015},
issn = {0022-0981},
keywords = {Cnidaria},
url = {http://www.sciencedirect.com/science/article/pii/S0022098111001274}
}
@ARTICLE{Spahn2010,
author = {Spahn, Martin and Kneitz, Susanne and Scholz, Claus-Jürgen and Stenger,
Nico and Rüdiger, Thomas and Ströbel, Philipp and Riedmiller, Hubertus
and Kneitz, Burkhard},
title = {Expression of microRNA-221 is progressively reduced in aggressive
prostate cancer and metastasis and predicts clinical recurrence},
journal = {Int. J. Cancer},
year = {2010},
volume = {127},
pages = {394--403},
number = {2},
abstract = {Abstract 10.1002/ijc.24715.abs Emerging evidence shows that microRNAs
(miR) are involved in the pathogenesis of a variety of cancers, including
prostate carcinoma (PCa). Little information is available regarding
miR expression levels in lymph node metastasis of prostate cancer
or the potential of miRs as prognostic markers in this disease. Therefore,
we analyzed the global expression of miRs in benign, hyperplastic
prostate tissue (BPH), primary PCa of a high risk group of PCa patients,
and corresponding metastatic tissues by microarray analysis. Consistent
with the proposal that some miRs are oncomirs, we found aberrant
expression of several miRs, including the downregulation of miR-221,
in PCa metastasis. Downregulation of miR-221 was negatively correlated
with the expression of the proto-oncogen c-kit in primary carcinoma.
In a large study cohort, the prostate-specific oncomir miR-221 was
progressively downregulated in aggressive forms of PCa. Downregulation
of miR-221 was associated with clinicopathological parameters, including
the Gleason score and the clinical recurrence during follow up. Kaplan–Meier
estimates and Cox proportional hazard models showed that miR-221
downregulation was linked to tumor progression and recurrence in
a high risk prostate cancer cohort. Our results showed that progressive
miR-221 downregulation hallmarks metastasis and presents a novel
prognostic marker in high risk PCa. This suggests that miR-221 has
potential as a diagnostic marker and therapeutic target in PCa.},
issn = {1097-0215},
keywords = {microRNA, high risk prostate carcinoma, metastasis, miR-221, prognosis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24715}
}
@ARTICLE{Spalenza2011,
author = {Veronica Spalenza and Flavia Girolami and Claudia Bevilacqua and
Fulvio Riondato and Roberto Rasero and Carlo Nebbia and Paola Sacchi
and Patrice Martin},
title = {Identification of internal control genes for quantitative expression
analysis by real-time PCR in bovine peripheral lymphocytes},
journal = {The Veterinary Journal},
year = {2011},
volume = {189},
pages = {278 - 283},
number = {3},
abstract = {Gene expression studies in blood cells, particularly lymphocytes,
are useful for monitoring potential exposure to toxicants or environmental
pollutants in humans and livestock species. Quantitative PCR is the
method of choice for obtaining accurate quantification of mRNA transcripts
although variations in the amount of starting material, enzymatic
efficiency, and the presence of inhibitors can lead to evaluation
errors. As a result, normalization of data is of crucial importance.
The most common approach is the use of endogenous reference genes
as an internal control, whose expression should ideally not vary
among individuals and under different experimental conditions. The
accurate selection of reference genes is therefore an important step
in interpreting quantitative PCR studies.
Since no systematic investigation in bovine lymphocytes has been performed,
the aim of the present study was to assess the expression stability
of seven candidate reference genes in circulating lymphocytes collected
from 15 dairy cows. Following the characterization by flow cytometric
analysis of the cell populations obtained from blood through a density
gradient procedure, three popular softwares were used to evaluate
the gene expression data. The results showed that two genes are sufficient
for normalization of quantitative PCR studies in cattle lymphocytes
and that YWAHZ, S24 and PPIA are the most stable genes.},
doi = {10.1016/j.tvjl.2010.11.017},
issn = {1090-0233},
keywords = {Reference genes},
url = {http://www.sciencedirect.com/science/article/pii/S1090023310004041}
}
@ARTICLE{Span2009,
author = {Span, P.N. and Sieuwerts, A.M. and Heuvel, J.J.T.M. and Spyratos,
F. and Duffy, M.J. and Eppenberger-Castori, S. and Vacher, S. and
O'Brien, K. and McKiernan, E. and Pierce, A. and Vuaroqueaux, V.
and Foekens, J.A. and Sweep, F.C.G.J. and Martens, J.W.M.},
title = {Harmonisation of multi-centre real-time reverse-transcribed PCR results
of a candidate prognostic marker in breast cancer: An EU-FP6 supported
study of members of the EORTC - PathoBiology Group},
journal = {European Journal of Cancer},
year = {2009},
volume = {45},
pages = {74--81},
number = {1},
month = jan,
abstract = {Aim Assessment of intra- and inter-laboratory variation in multi-centre
real-time reverse-transcribed PCR (qRT-PCR)-based mRNA quantification
of a prognostic marker in breast cancer using external quality assurance
(EQA).Methods A questionnaire on the methodologies used and EQA calibrators
were sent to 5 participating laboratories from 4 European countries,
which measured mRNA levels of PITX2 splice variants and reference
genes by qRT-PCR.Results Differences in the methodology included
PCR quantification methodology and equipment, RNA extraction and
cDNA synthesis procedures. The intra-laboratory coefficient of variation
(CV) ranged from 5 to 23%, and the inter-laboratory CV ranged from
17 to 30%. The inter-laboratory CV was reduced to 13% by using prediluted
calibrators and by harmonising the data in the central QA laboratory.
Additional normalisation using reference genes did not decrease the
variation further.Conclusions Both externally provided calibrators
and centralised harmonisation are required to reduce the intra-laboratory
variation in multi-centre qRT-PCR results to an acceptable level.},
issn = {0959-8049},
keywords = {Quality assurance, Quality control, Multi-centre studies, Reverse
transcriptase polymerase chain reaction, Biomarkers},
url = {http://www.sciencedirect.com/science/article/B6T68-4TX12DX-5/2/2d0ff2b9bd788509db4911962065c557}
}
@ARTICLE{Spaniolas2006,
author = {Spaniolas, Stelios and May, Sean T. and Bennett, Malcolm J. and Tucker,
Gregory A.},
title = {Authentication of Coffee by Means of PCR-RFLP Analysis and Lab-on-a-Chip
Capillary Electrophoresis},
journal = {Journal of Agricultural and Food Chemistry},
year = {2006},
volume = {54},
pages = {7466-7470},
number = {20},
doi = {10.1021/jf061164n},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf061164n},
url = {http://pubs.acs.org/doi/abs/10.1021/jf061164n}
}
@ARTICLE{Spaniolas2008,
author = {Spaniolas, Stelios and Tsachaki, Maroussa and Bennett, Malcolm J.
and Tucker, Gregory A.},
title = {Toward the Authentication of Wines of Nemea Denomination of Origin
through Cleaved Amplified Polymorphic Sequence (CAPS)-Based Assay},
journal = {Journal of Agricultural and Food Chemistry},
year = {2008},
volume = {56},
pages = {7667-7671},
number = {17},
note = {PMID: 18698791},
doi = {10.1021/jf801036f},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf801036f},
url = {http://pubs.acs.org/doi/abs/10.1021/jf801036f}
}
@ARTICLE{Sparfel2010,
author = {Sparfel, Lydie and Pinel-Marie, Marie-Laure and Boize, Magali and
Koscielny, Serge and Desmots, Sophie and Pery, Alexandre and Fardel,
Olivier},
title = {Transcriptional Signature of Human Macrophages Exposed to the Environmental
Contaminant Benzo(a)pyrene},
journal = {Toxicol. Sci.},
year = {2010},
volume = {114},
pages = {247--259},
number = {2},
month = apr,
abstract = {Polycyclic aromatic hydrocarbons (PAHs) are widely distributed immunotoxic
and carcinogenic environmental contaminants, known to affect macrophages.
In order to identify their molecular targets in such cells, we have
analyzed gene expression profile of primary human macrophages treated
by the prototypical PAH benzo(a)pyrene (BaP), using pangenomic oligonucleotides
microarrays. Exposure of macrophages to BaP for 8 and 24 h resulted
in 96 and 1100 genes, differentially expressed by at least a twofold
change factor, respectively. Some of these targets, including the
chemokine receptor CXCR5, the G protein-coupled receptor 35 (GPR35),
and the Ras regulator RASAL1, have not been previously shown to be
affected by PAHs, in contrast to others, such as interleukin-1{beta}
and the aryl hydrocarbon receptor (AhR) repressor. These BaP-mediated
gene regulations were fully validated by reverse transcription-quantitative
polymerase chain reaction assays for some selected genes. Their bioinformatic
analysis indicated that biological functions linked to immunity,
inflammation, and cell death were among the most affected by BaP
in human macrophages and that the AhR and p53 signaling pathways
were the most significant canonical pathways activated by the PAH.
AhR and p53 implications were moreover fully confirmed by the prevention
of BaP-related upregulation of some selected target genes by AhR
silencing or the use of pifithrin-{alpha}, an inhibitor of PAH bioactivation-related
DNA damage/p53 pathways. Overall, these data, through identifying
genes and signaling pathways targeted by PAHs in human macrophages,
may contribute to better understand the molecular basis of the immunotoxicity
of these environmental contaminants.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/114/2/247}
}
@ARTICLE{Sparks2009,
author = {Sparks, Lauren M. and Pasarica, Magdalena and Sereda, Olga and deJonge,
Lilian and Thomas, Shantele and Loggins, Heather and Xie, Hui and
Miles, John M. and Smith, Steven R.},
title = {Effect of adipose tissue on the sexual dimorphism in metabolic flexibility},
journal = {Metabolism},
year = {2009},
volume = {58},
pages = {1564--1571},
number = {11},
month = nov,
abstract = {Metabolic flexibility is the ability to transition between fat oxidation
(fasting state) and glucose oxidation (fed state). We hypothesized
that adipose tissue inflammation and lipid metabolism contribute
to sexual dimorphism in metabolic flexibility. Respiratory quotient
([Delta]RQ, metabolic flexibility) and nonesterified fatty acids
(NEFAs) before and during euglycemic-hyperinsulinemic clamp were
measured in healthy young women (n = 22) and men (n = 56). Adiponectin
levels were measured in plasma. Abdominal subcutaneous adipose tissue
gene expression was measured by quantitative reverse transcriptase
polymerase chain reaction. As compared with men, women had higher
[Delta]RQ (0.14 ± 0.04 vs 0.09 ± 0.04, P < .01). Fasting RQ and fat
cell size were not different between sexes. As compared with men,
women had lower insulin-suppressed NEFAs (P < .05); greater adiponectin
levels; and higher expression of adipogenesis, fatty acid storage,
and oxidation genes (PPAR[gamma]2, PCK1, SCD1, and PPAR[alpha]; P
< .05). There were no sex differences in messenger RNA of macrophage
markers or chemokines. Stepwise regression analysis revealed that
the only adipose tissue characteristics that influenced metabolic
flexibility in women were SCD1 and PCK1 messenger RNA (model R2 =
0.49, P < .05); in men, these were serum adiponectin and insulin-suppressed
NEFAs (model R2 = 0.34, P < .05). Healthy young women are more metabolically
flexible than men, driven by an increase in insulin-stimulated glucose
oxidation rather than differences in fasting fat oxidation. Women
have greater capacity for insulin suppression of NEFAs despite similar
chemokine and macrophage content in adipose tissue. Combined, these
results provide evidence for a role of adipose tissue characteristics
in the sexual dimorphism of metabolic flexibility.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/B6WN4-4WRD6DM-3/2/cb04aa7de714630add4bdcafe7d77c06}
}
@ARTICLE{Sparks2009a,
author = {Sparks, Lauren M. and Ukropcova, Barbara and Smith, Jana and Pasarica,
Magdalena and Hymel, David and Xie, Hui and Bray, George A. and Miles,
John M. and Smith, Steven R.},
title = {Relation of adipose tissue to metabolic flexibility},
journal = {Diabetes Research and Clinical Practice},
year = {2009},
volume = {83},
pages = {32--43},
number = {1},
month = jan,
abstract = {Metabolic flexibility is the capacity for skeletal muscle to shift
reliance between lipids and glucose during fasting or in response
to insulin. We hypothesized that body fat, adipose tissue characteristics,
e.g. larger adipocytes, presence of inflammatory gene markers and
impaired suppression of non-esterified fatty acids (NEFAs) during
insulin infusion might be related to metabolic flexibility. We measured
changes in respiratory quotient ([Delta]RQ) before and during euglycemic-hyperinsulinemic
clamp in healthy young males. Body fat by DXA, laboratory measurements,
abdominal subcutaneous adipose tissue biopsies and fat cell size
(FCS) were obtained after an overnight fast. Gene expression for
17 adipose tissue genes related to lipid synthesis, uptake, oxidation
and storage, lipolysis and inflammation were measured. Reduced metabolic
flexibility was associated with higher body fat, larger FCS and impaired
insulin suppression of NEFAs. Metabolic flexibility was associated
with higher serum adiponectin levels. Lower adipose tissue gene expression
for inflammation markers was associated with greater NEFA suppression
by insulin and metabolic flexibility. Combined, these results indicate
that body fat, larger adipocytes, failure of insulin to suppress
NEFAs, decreased adiponectin levels and inflammation markers in adipose
tissue are associated with decreased insulin-stimulated glucose uptake
and oxidation, which is an important component of reduced metabolic
flexibility.},
issn = {0168-8227},
keywords = {Fat cell size, Non-esterified free fatty acids, Euglycemic-hyperinsulinemic
clamp, Adipose tissue, Metabolic flexibility, Inflammatory markers,
Adiponectin},
url = {http://www.sciencedirect.com/science/article/B6T5Y-4V11H90-1/2/591fff930fdc78698d717351762ae4ae}
}
@ARTICLE{Sparks2006,
author = {Sparks, Lauren M. and Xie, Hui and Koza, Robert A. and Mynatt, Randall
and Bray, George A. and Smith, Steven R.},
title = {High-fat/low-carbohydrate diets regulate glucose metabolism via a
long-term transcriptional loop},
journal = {Metabolism},
year = {2006},
volume = {55},
pages = {1457--1463},
number = {11},
month = nov,
abstract = {Insulin sensitivity is characterized by insulin-stimulated glucose
metabolism in skeletal muscle. We hypothesized that carbohydrate
metabolism and storage might be under transcriptional control. To
test this hypothesis, we fed insulin-sensitive males (glucose disposal
rate, 14.7 ± 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic
high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies
before and after intervention. Oligonucleotide microarrays revealed
a total of 369 genes of 18 861 genes on the arrays were differentially
regulated in response to diet (Bonferonni adjusted P < .01). A similar
experiment was conducted in mice with a 3-week intervention using
a control group and an HF/LCD group to offset the lack of a control
group within the human cohort. As part of an analysis of results
previously published from this data set, 7 genes in the carbohydrate
metabolism pathway changed in response to the HF/LCD, and 3 genes
were confirmed by quantitative reverse transcriptase-polymerase chain
reaction: fructose-2,6-biphosphatase 3 (PFKFB3), pyruvate dehydrogenase
kinase, isoenzyme 4 (PDK4), and glycogen synthase 1 (muscle). In
a separate experiment, we fed C57Bl/6J mice an HF/LCD for 3 weeks
and found that the same glucose metabolism genes were changed by
~70% on average. Fructose-2,6-biphosphatase 3 and pyruvate dehydrogenase
kinase, isoenzyme 4 increased and glycogen synthase 1 (muscle) decreased.
Combined, these results suggest a mechanism whereby HF/LCD regulates
the genes necessary for glucose utilization and storage vis-á-vis
transcriptional control.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/B6WN4-4M3YXH7-8/2/15665eb6d2bc4b11027667209047a8bd}
}
@ARTICLE{Sparks2005,
author = {Sparks, Lauren M. and Xie, Hui and Koza, Robert A. and Mynatt, Randall
and Hulver, Matthew W. and Bray, George A. and Smith, Steven R.},
title = {A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial
Oxidative Phosphorylation in Skeletal Muscle},
journal = {Diabetes},
year = {2005},
volume = {54},
pages = {1926--1933},
number = {7},
month = jul,
abstract = {Obesity and type 2 diabetes have been associated with a high-fat diet
(HFD) and reduced mitochondrial mass and function. We hypothesized
a HFD may affect expression of genes involved in mitochondrial function
and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive
males an isoenergetic HFD for 3 days with muscle biopsies before
and after intervention. Oligonucleotide microarray analysis revealed
297 genes were differentially regulated by the HFD (Bonferonni adjusted
P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS)
decreased. Four were members of mitochondrial complex I: NDUFB3,
NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial
carrier protein SLC25A12. Peroxisome proliferator-activated receptor
{gamma} coactivator-1 (PGC1) {alpha} and PGC1{beta} mRNA were decreased
by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate
experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that
the same OXPHOS and PGC1 mRNAs were downregulated by [~]90%, cytochrome
C and PGC1{alpha} protein by [~]40%. Combined, these results suggest
a mechanism whereby HFD downregulates genes necessary for OXPHOS
and mitochondrial biogenesis. These changes mimic those observed
in diabetes and insulin resistance and, if sustained, may result
in mitochondrial dysfunction in the prediabetic/insulin-resistant
state.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/54/7/1926}
}
@ARTICLE{Spee2010,
author = {Spee, Bart and Carpino, Guido and Schotanus, Baukje A and Katoonizadeh,
Azeam and Borght, Sara Vander and Gaudio, Eugenio and Roskams, Tania},
title = {Characterisation of the liver progenitor cell niche in liver diseases:
potential involvement of Wnt and Notch signalling},
journal = {Gut},
year = {2010},
volume = {59},
pages = {247--257},
number = {2},
month = feb,
abstract = {BackgroundHepatic progenitor cells (HPCs) hold a great potential for
therapeutic intervention for currently untreatable liver diseases.
However, in human diseases molecular mechanisms involved in proliferation
and differentiation of HPCs are poorly understood. Methods and resultsIn
the present study activated HPCs and their microenvironment (niche)
were investigated in acute and chronic human liver disease by gene-expression
analysis and immunohistochemistry/immunofluorescence. Cryopreserved
liver tissues were used from patients with parenchymal versus biliary
diseases: acute necrotising hepatitis (AH), cirrhosis after hepatitis
C infection, and primary biliary cirrhosis in order to study differentiation
of HPCs towards hepatocytic versus biliary lineage. Keratin 7 positive
HPCs/reactive ductules were captured by means of laser capture microdissection
and gene-expression profiles were obtained by using a customised
PCR array. Gene expression results were confirmed by immunohistochemistry
and immunofluorescence double staining. In all disease groups, microdissected
HPCs expressed progenitor cell markers such as KRT7, KRT19, NCAM,
ABCG2, LIF, KIT, OCT4, CD44 and TERT. In AH, HPCs were most activated
and showed a high expression of prominin-1 (CD133) and{alpha} -fetoprotein,
and a strong activation of the Wnt pathway. In contrast to parenchymal
diseases, HPCs in primary biliary cirrhosis (biliary differentiation)
showed a high activation of Notch signalling. ConclusionA distinct
pattern of HPC surface markers was found between acute and chronic
liver diseases. Similar to what is known from animal experiments,
strong evidence has been found signifying the role of Wnt signalling
in proliferation of human HPCs whereas Notch signalling is involved
in biliary differentiation. These pathways can be targeted in future
therapies.},
url = {http://gut.bmj.com/cgi/content/abstract/59/2/247}
}
@ARTICLE{Spehlmann2009,
author = {Spehlmann, Martina E. and Dann, Sara M. and Hruz, Petr and Hanson,
Elaine and McCole, Declan F. and Eckmann, Lars},
title = {CXCR2-Dependent Mucosal Neutrophil Influx Protects against Colitis-Associated
Diarrhea Caused by an Attaching/Effacing Lesion-Forming Bacterial
Pathogen},
journal = {J. Immunol.},
year = {2009},
volume = {183},
pages = {3332--3343},
number = {5},
month = sep,
abstract = {Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal
disease in young children, yet symptoms and duration are highly variable
for unknown reasons. Citrobacter rodentium, a murine model pathogen
that shares important functional features with EPEC, colonizes mice
in colon and cecum and causes inflammation, but typically little
or no diarrhea. We conducted genome-wide microarray studies to define
mechanisms of host defense and disease in C. rodentium infection.
A significant fraction of the genes most highly induced in the colon
by infection encoded CXC chemokines, particularly CXCL1/2/5 and CXCL9/10,
which are ligands for the chemokine receptors CXCR2 and CXCR3, respectively.
CD11b+ dendritic cells were the major producers of CXCL1, CXCL5,
and CXCL9, while CXCL2 was mainly induced in macrophages. Infection
of gene-targeted mice revealed that CXCR3 had a significant but modest
role in defense against C. rodentium, whereas CXCR2 had a major and
indispensable function. CXCR2 was required for normal mucosal influx
of neutrophils, which act as direct antibacterial effectors. Moreover,
CXCR2 loss led to severe diarrhea and failure to express critical
components of normal ion and fluid transport, including ATPase {beta}2-subunit,
CFTR, and DRA. The antidiarrheal functions were unique to CXCR2,
since other immune defects leading to increased bacterial load and
inflammation did not cause diarrhea. Thus, CXCR2-dependent processes,
particularly mucosal neutrophil influx, not only contribute to host
defense against C. rodentium, but provide protection against infection-associated
diarrhea.},
url = {http://www.jimmunol.org/cgi/content/abstract/183/5/3332}
}
@ARTICLE{Spellmann2011,
author = {Spellmann, Ilja and Rujescu, Dan and Musil, Richard and Mayr, Andreas
and Giegling, Ina and Genius, Just and Zill, Peter and Dehning, Sandra
and Opgen-Rhein, Markus and Cerovecki, Anja and Hartmann, Annette
M. and Schäfer, Martin and Bondy, Brigitta and Müller, Norbert and
Möller, Hans-Jürgen and Riedel, Michael},
title = {Homer-1 polymorphisms are associated with psychopathology and response
to treatment in schizophrenic patients},
journal = {Journal of Psychiatric Research},
year = {2011},
volume = {45},
pages = {234--241},
number = {2},
month = feb,
abstract = {The HOMER 1 protein plays a crucial role in mediating glutamatergic
neurotransmission. It has previously shown to be a candidate gene
for etiology and pathophysiology of different psychiatric diseases
such as schizophrenia. To identify genes involved in response to
antipsychotics, subgroups of animals were treated with haloperidol
(1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray
data, we replicated the observed increase of Homer 1 gene expression.
Furthermore, we genotyped 267 schizophrenic patients, who were treated
monotherapeutically with different antipsychotics within randomized-controlled
trials. Psychopathology was measured weekly using the PANSS for a
minimum of four and a maximum of twelve weeks. Correlations between
PANSS subscale scores at baseline and PANSS improvement scores after
four weeks of treatment and genotypes were calculated by using a
linear model for all investigated SNP's. We found an association
between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different
PANSS subscales at baseline. Furthermore all seven investigated polymorphisms
were found to be associated with therapy response in terms of a significant
correlation with different PANSS improvement subscores after four
weeks of antipsychotic treatment. Most significant associations have
been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales
both at baseline conditions and after four weeks of antipsychotic
treatment. This is the first study which shows an association between
HOMER 1 polymorphisms and psychopathology data at baseline and therapy
response in a clinical sample of schizophrenic patients. Thus, these
data might further help in detecting differential therapy response
in individuals with schizophrenia.},
issn = {0022-3956},
keywords = {Homer 1, Schizophrenia, Antipsychotics, Therapy response, Pharmacogenetics,
Glutamate},
url = {http://www.sciencedirect.com/science/article/pii/S0022395610001822}
}
@ARTICLE{Spencer2011,
author = {Spencer, Carrie and Montalvo, John and Mclaughlin, Sarah R. and Bryan,
Brad A.},
title = {Small Molecule Inhibition of Cytoskeletal Dynamics in Melanoma Tumors
Results in Altered Transcriptional Expression Patterns of Key Genes
Involved in Tumor Initiation and Progression},
journal = {Cancer Genomics Proteomics},
year = {2011},
volume = {8},
pages = {77--85},
number = {2},
month = mar,
abstract = {Background: Rho kinase signaling plays an important role in the oncogenic
process largely through its regulation of F-actin dynamics, and inhibition
of this pathway results in reduction in tumor volume and metastasis
across a number of tumor types. While the cytoskeletal-regulatory
role of Rho kinase has been a topic of in-depth study, the mechanisms
linking Rho kinase to altered gene expression are largely unknown.
Materials and Methods: Global gene expression analysis was performed
on melanoma tumors treated with sham or the small molecule inhibitor
Y27632. Results: Inhibition of Rho kinase activity in melanoma tumors
results in a statistically significant change in gene transcription
of 94 genes, many of which are critically involved in tumor initiation
and progression. Conclusion: In addition to regulating tumorigenesis
through modulation of the phosphoproteome, Rho kinase signaling also
contributes to the regulation of the tumor transcriptome.},
url = {http://cgp.iiarjournals.org/cgi/content/abstract/8/2/77}
}
@ARTICLE{Spencer2010,
author = {Spencer, Michael and Yao-Borengasser, Aiwei and Unal, Resat and Rasouli,
Neda and Gurley, Catherine M. and Zhu, Beibei and Peterson, Charlotte
A. and Kern, Philip A.},
title = {Adipose tissue macrophages in insulin-resistant subjects are associated
with collagen VI and fibrosis and demonstrate alternative activation},
journal = {Am J Physiol Endocrinol Metab},
year = {2010},
volume = {299},
pages = {E1016--1027},
number = {6},
month = dec,
abstract = {Adipose tissue macrophages are associated with insulin resistance
and are linked to changes in the extracellular matrix. To better
characterize adipose macrophages, the extracellular matrix, and adipocyte-macrophage
interactions, gene expression from adipose tissue and the stromal
vascular fraction was assessed for markers of inflammation and fibrosis,
and macrophages from obese and lean subjects were counted and characterized
immunohistochemically. Coculture experiments examined the effects
of adipocyte-macrophage interaction. Collagen VI gene expression
was associated with insulin sensitivity and CD68 (r = -0.56 and 0.60,
P < 0.0001) and with other markers of inflammation and fibrosis.
Compared with adipose tissue from lean subjects, adipose tissue from
obese subjects contained increased areas of fibrosis, which correlated
inversely with insulin sensitivity (r = -0.58, P < 0.02) and positively
with macrophage number (r = 0.70, P < 0.01). Although macrophages
in crownlike structures (CLS) were more abundant in obese adipose
tissue, the majority of macrophages were associated with fibrosis
and were not organized in CLS. Macrophages in CLS were predominantly
M1, but most other macrophages, particularly those in fibrotic areas,
were M2 and also expressed CD150, a marker of M2c macrophages. Coculture
of THP-1 macrophages with adipocytes promoted the M2 phenotype, with
a lower level of IL-1 expression and a higher ratio of IL-10 to IL-12.
Transforming growth factor-{beta} (TGF-{beta}) was more abundant
in M2 macrophages and was further increased by coculture with adipocytes.
Downstream effectors of TGF-{beta}, such as plasminogen activator
inhibitor-1, collagen VI, and phosphorylated Smad, were increased
in macrophages and adipocytes. Thus adipose tissue of insulin-resistant
humans demonstrated increased fibrosis, M2 macrophage abundance,
and TGF-{beta} activity.},
comment = {10.1152/ajpendo.00329.2010},
url = {http://ajpendo.physiology.org/cgi/content/abstract/299/6/E1016}
}
@ARTICLE{Spencer2007,
author = {Spencer, Matthew W.B. and Casson, Stuart A. and Lindsey, Keith},
title = {Transcriptional Profiling of the Arabidopsis Embryo},
journal = {Plant Physiology},
year = {2007},
volume = {143},
pages = {924--940},
number = {2},
month = feb,
abstract = {We have used laser-capture microdissection to isolate RNA from discrete
tissues of globular, heart, and torpedo stage embryos of Arabidopsis
(Arabidopsis thaliana). This was amplified and analyzed by DNA microarray
using the Affymetrix ATH1 GeneChip, representing approximately 22,800
Arabidopsis genes. Cluster analysis showed that spatial differences
in gene expression were less significant than temporal differences.
Time course analysis reveals the dynamics and complexity of gene
expression in both apical and basal domains of the developing embryo,
with several classes of synexpressed genes identifiable. The transition
from globular to heart stage is associated in particular with an
up-regulation of genes involved in cell cycle control, transcriptional
regulation, and energetics and metabolism. The transition from heart
to torpedo stage is associated with a repression of cell cycle genes
and an up-regulation of genes encoding storage proteins, and pathways
of cell growth, energy, and metabolism. The torpedo stage embryo
shows strong functional differentiation in the root and cotyledon,
as inferred from the classes of genes expressed in these tissues.
The time course of expression of the essential EMBRYO-DEFECTIVE genes
shows that most are expressed at unchanging levels across all stages
of embryogenesis. We show how identified genes can be used to generate
cell type-specific markers and promoter activities for future application
in cell biology.},
url = {http://www.plantphysiol.org/cgi/content/abstract/143/2/924}
}
@ARTICLE{Spens2009,
author = {Spens, Erika and Häggström, Lena},
title = {Proliferation of NS0 cells in protein-free medium: The role of cell-derived
proteins, known growth factors and cellular receptors},
journal = {Journal of Biotechnology},
year = {2009},
volume = {141},
pages = {123--129},
number = {3-4},
month = may,
abstract = {NS0 cells proliferate without external supply of growth factors in
protein-free media. We hypothesize that the cells produce their own
factors to support proliferation. Understanding the mechanisms behind
this autocrine regulation of proliferation may open for the novel
approaches to improve animal cell processes. The following proteins
were identified in NS0 conditioned medium (CM): cyclophilin A, cyclophilin
B (CypB), cystatin C, D-dopachrome tautomerase, IL-25, isopentenyl-diphosphate
delta-isomerase, macrophage migration inhibitory factor (MIF), [beta]2-microglobulin,
Niemann pick type C2, secretory leukocyte protease inhibitor, thioredoxin-1,
TNF-[alpha], tumour protein translationally controlled 1 and ubiquitin.
Further, cDNA microarray analysis indicated that the genes for IL-11,
TNF receptor 6, TGF-[beta] receptor 1 and the IFN-[gamma] receptor
were transcribed. CypB, IFN-[alpha]/[beta]/[gamma], IL-11, IL-25,
MIF, TGF-[beta] and TNF-[alpha] as well as the known growth factors
EGF, IGF-I/II, IL-6, leukaemia inhibitory factor and oncostatin M
(OSM) were excluded as involved in autocrine regulation of NS0 cell
proliferation. The receptors for TGF-[beta], IGF and OSM are however
present in NS0 cell membranes since TGF-[beta]1 caused cell death,
and IGF-I/II and OSM improved cell growth. Even though no ligand
was found, the receptor subunit gp130, active in signal transduction
of the IL-6 like proteins, was shown to be essential for NS0 cells
as demonstrated by siRNA gene silencing.},
issn = {0168-1656},
keywords = {NS0 myeloma cells, Autocrine growth factors, Regulation of proliferation,
Conditioned medium, gp130},
url = {http://www.sciencedirect.com/science/article/B6T3C-4VXB8PD-1/2/ea0d1e4ab6cca7da718a6c416f819816}
}
@ARTICLE{Sperandio2008,
author = {Sperandio, Brice and Regnault, Beatrice and Guo, Jianhua and Zhang,
Zhi and Stanley, Samuel L., Jr. and Sansonetti, Philippe J. and Pedron,
Thierry},
title = {Virulent Shigella flexneri subverts the host innate immune response
through manipulation of antimicrobial peptide gene expression},
journal = {J. Exp. Med.},
year = {2008},
volume = {205},
pages = {1121--1132},
number = {5},
month = may,
abstract = {Antimicrobial factors are efficient defense components of the innate
immunity, playing a crucial role in the intestinal homeostasis and
protection against pathogens. In this study, we report that upon
infection of polarized human intestinal cells in vitro, virulent
Shigella flexneri suppress transcription of several genes encoding
antimicrobial cationic peptides, particularly the human {beta}-defensin
hBD-3, which we show to be especially active against S. flexneri.
This is an example of targeted survival strategy. We also identify
the MxiE bacterial regulator, which controls a regulon encompassing
a set of virulence plasmid-encoded effectors injected into host cells
and regulating innate signaling, as being responsible for this dedicated
regulatory process. In vivo, in a model of human intestinal xenotransplant,
we confirm at the transcriptional and translational level, the presence
of a dedicated MxiE-dependent system allowing S. flexneri to suppress
expression of antimicrobial cationic peptides and promoting its deeper
progression toward intestinal crypts. We demonstrate that this system
is also able to down-regulate additional innate immunity genes, such
as the chemokine CCL20 gene, leading to compromised recruitment of
dendritic cells to the lamina propria of infected tissues. Thus,
S. flexneri has developed a dedicated strategy to weaken the innate
immunity to manage its survival and colonization ability in the intestine.},
url = {http://jem.rupress.org/cgi/content/abstract/205/5/1121}
}
@ARTICLE{Sperandio2009,
author = {Sperandio, Sabina and Fortin, Jessyka and Sasik, Roman and Robitaille,
Lynda and Corbeil, Jacques and de Belle, Ian},
title = {The transcription factor Egr1 regulates the HIF-1α gene during hypoxia},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {38--44},
number = {1},
abstract = {Abstract 10.1002/mc.20454.abs Using oligonucleotide expression microarrays
we have examined the modulation of gene expression in the DU145 prostate
cancer cell line. Our findings confirm that the Egr1 transcription
factor is rapidly and transiently upregulated by hypoxia. Furthermore,
we have demonstrated that HIF-1α mRNA is also transiently upregulated,
as is its target gene VEGF. To elucidate the mechanism of the transcriptional
upregulation of the HIF-1α gene, we have shown that Egr1 is able
to directly bind to the HIF-1α promoter using chromatin immunoprecipitation.
We also provide evidence that the binding of Egr1 is necessary for
the trans-activation of the HIF-1α promoter. These studies highlight
the importance for the Egr1 transcription factor in the hypoxic response
in cultured prostate cancer cell lines, and indicate that the response
of Egr1 is upstream of HIF-1 in these cells. These studies are the
first demonstration that the HIF-1α transcription factor is targeted
directly by Egr1 in hypoxia. © 2008 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {Erg1, hypoxia, HIF1},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20454}
}
@ARTICLE{Speziani2007,
author = {Speziani, Carole and Rivollier, Aymeric and Gallois, Anne and Coury,
Fabienne and Mazzorana, Marlène and Azocar, Olga and Flacher, Monique
and Bella, Chantal and Tebib, Jacques and Jurdic, Pierre and Rabourdin-Combe,
Chantal and Delprat, Christine},
title = {Murine dendritic cell transdifferentiation into osteoclasts is differentially
regulated by innate and adaptive cytokines},
journal = {Eur. J. Immunol.},
year = {2007},
volume = {37},
pages = {747--757},
number = {3},
abstract = {Abstract 10.1002/eji.200636534.abs Dendritic cells (DC) are the mononuclear
cells that initiate adaptive immune responses. Osteoclasts (OC) are
the multinucleated giant cells that resorb bone. As previously described
for human conventional DC (cDC), we demonstrate that murine cDC,
either in vitro generated from Fms-like tyrosine kinase 3 (Flt3)+
bone marrow progenitors or ex vivo purified from spleen, are able
to develop into OC in response to M-CSF and receptor activator of
NF-κB ligand (RANKL) in vitro. This transdifferentiation is driven
by the immune environment that controls cDC maturation, cell fusion,
tartrate-resistant acid phosphatase (TRAP) and bone resorption activities.
Only immature cDC have the capacity to become OC since mature cDC
or plasmacytoid DC do not. Additions of the pro-inflammatory cytokines,
such as IL-1β and TNF-α, or human rheumatoid synovial fluid, increase
murine cDC transdifferentiation into OC, whereas IFN-α inhibits
it. The adaptive cytokine, IFN-γ, inhibits cDC fusion while IL-4
increases it. IL-2, IFN-γ and IL-4 inhibit TRAP and bone resorption
activities contrary to IL-10, which enhances both activities. A putative
new “immune multinucleated giant cell� unable to resorb bone,
which is formed owing to IL-4, is underlined. The future analysis
of cDC transdifferentiation into OC in murine models of inflammatory
arthritis will give us the quantitative importance of this phenomenon
in vivo.},
issn = {1521-4141},
keywords = {Cell differentiation, Cytokines, Dendritic cells, Rheumatoid arthritis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200636534}
}
@ARTICLE{Spicker2008,
author = {Spicker, Jeppe S. and Brunak, Soren and Frederiksen, Klaus S. and
Toft, Henrik},
title = {Integration of Clinical Chemistry, Expression, and Metabolite Data
Leads to Better Toxicological Class Separation},
journal = {Toxicol. Sci.},
year = {2008},
volume = {102},
pages = {444--454},
number = {2},
month = apr,
abstract = {A large number of databases are currently being implemented within
toxicology aiming to integrate diverse biological data, such as clinical
chemistry, expression, and other types of data. However, for these
endeavors to be successful, tools for integration, visualization,
and interpretation are needed. This paper presents a method for data
integration using a hierarchical model based on either principal
component analysis or partial least squares discriminant analysis
of clinical chemistry, expression, and nuclear magnetic resonance
data using a toxicological study as case. The study includes the
three toxicants alpha-naphthyl-isothiocyanate, dimethylnitrosamine,
and N-methylformamide administered to rats. Improved predictive ability
of the different classes is seen, suggesting that this approach is
a suitable method for data integration and visualization of biological
data. Furthermore, the method allows for correlation of biological
parameters between the different data types, which could lead to
an improvement in biological interpretation.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/102/2/444}
}
@ARTICLE{Spierings2011,
author = {Spierings, Diana C. and McGoldrick, Daniel and Hamilton-Easton, Ann
Marie and Neale, Geoffrey and Murchison, Elizabeth P. and Hannon,
Greg J. and Green, Douglas R. and Withoff, Sebo},
title = {Ordered progression of stage-specific miRNA profiles in the mouse
B2 B-cell lineage},
journal = {Blood},
year = {2011},
volume = {117},
pages = {5340--5349},
number = {20},
month = may,
abstract = {Micro-RNAs (miRNAs) have been recognized as critical regulators of
gene expression, and deregulation of miRNA expression has been implicated
in a wide spectrum of diseases. To provide a framework for the role
of miRNAs in B-cell development and malignancy, we deep-sequenced
miRNAs from B1 cells and 10 developmental stages that can be identified
within the mouse B2 B-cell lineage. The expression profiles of the
232 known miRNAs that are expressed during B-cell development display
stage-specific induction patterns, yet hierarchical clustering analysis
showed relationships that are in full agreement with the model of
the B2 B-cell developmental pathway. Analysis of exemplary miRNA
expression profiles (miR-150, miR-146a, miR-155, miR-181) confirmed
that our data are in agreement with previous results. The high resolution
of the expression data allowed for the identification of the sequential
expression of oncomir-1/miR-17-92 and its paralogs miR-106a-363 and
miR-106b-25 in subsequent developmental stages in the BM. Further,
we have identified and validated 45 novel miRNAs and 6 novel miRNA
candidates expressed in developing B cells.},
comment = {10.1182/blood-2010-10-316034},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/20/5340}
}
@ARTICLE{Spies2010,
author = {Spies, Cornelia M. and Gaber, Timo and Hahne, Martin and Naumann,
Lydia and Tripmacher, Robert and Schellmann, Saskia and Stahn, Cindy
and Burmester, Gerd-Rüdiger and Radbruch, Andreas and Buttgereit,
Frank},
title = {Rimexolone inhibits proliferation, cytokine expression and signal
transduction of human CD4+ T-cells},
journal = {Immunology Letters},
year = {2010},
volume = {131},
pages = {24--32},
number = {1},
month = jun,
abstract = {Rimexolone is a lipophilic glucocorticoid drug used for local application.
Only few data are available describing its effects on immune cell
functions. In this study we investigated the effects of rimexolone
on the proliferation of human CD4+ T-cells using dexamethasone as
standard reference. Isolated CD4+ T-cells were pre-incubated with
rimexolone or dexamethasone at different concentrations for 10 min
(10-11/10-8/10-5 M) and stimulated with anti-CD3/anti-CD28 for 96 h.
Proliferation was determined by flow cytometry. The percentage of
dividing cells was significantly reduced by 10-5 M rimexolone and
dexamethasone; however, the average number of cell divisions was
unchanged. In addition, production of IL-2 and other cytokines was
reduced by both glucocorticoids at 10-5 M. Interestingly, we observed
a rimexolone-induced down-regulation of CD4 expression in unstimulated
and non-dividing cells. The inhibitory effects on proliferation and
CD4 expression could be blocked by the glucocorticoid-antagonist
RU486 and were not due to glucocorticoid-induced apoptosis. Rimexolone
and dexamethasone showed a similar potential to induce I[kappa]B[alpha]
gene expression. We demonstrate rimexolone and dexamethasone to impair
T-cell signalling pathways by rapid non-genomic suppression of the
phosphorylation of Akt, p38 and ERK. We conclude that rimexolone
and dexamethasone inhibit T-cell proliferation as well as cytokine
production of activated CD4+ T-cells in a similar manner. As these
inhibitory effects predominantly occur at high concentrations, a
relatively high occupation-rate of cytosolic glucocorticoid receptors
is needed, but receptor-mediated non-genomic effects may also be
involved. It is implied that these effects contribute to the well-known
beneficial anti-inflammatory and immunomodulatory effects of glucocorticoid
therapy.},
issn = {0165-2478},
keywords = {Glucocorticoid, Dexamethasone, Rimexolone, T-cells, Proliferation,
Cytokine, Genomic, Non-genomic, CD4 expression},
url = {http://www.sciencedirect.com/science/article/B6T75-4YRXCXF-1/2/016346b6a2db572208c0a73e32416052}
}
@ARTICLE{Spiess2008,
author = {Spiess, Andrej-Nikolai and Feig, Caroline and Ritz, Christian},
title = {Highly accurate sigmoidal fitting of real-time PCR data by introducing
a parameter for asymmetry},
journal = {BMC Bioinformatics},
year = {2008},
volume = {9},
pages = {221},
number = {1},
abstract = {BACKGROUND:Fitting four-parameter sigmoidal models is one of the methods
established in the analysis of quantitative real-time PCR (qPCR)
data. We had observed that these models are not optimal in the fitting
outcome due to the inherent constraint of symmetry around the point
of inflection. Thus, we found it necessary to employ a mathematical
algorithm that circumvents this problem and which utilizes an additional
parameter for accommodating asymmetrical structures in sigmoidal
qPCR data.RESULTS:The four-parameter models were compared to their
five-parameter counterparts by means of nested F-tests based on the
residual variance, thus acquiring a statistical measure for higher
performance. For nearly all qPCR data we examined, five-parameter
models resulted in a significantly better fit. Furthermore, accuracy
and precision for the estimation of efficiencies and calculation
of quantitative ratios were assessed with four independent dilution
datasets and compared to the most commonly used quantification methods.
It could be shown that the five-parameter model exhibits an accuracy
and precision more similar to the non-sigmoidal quantification methods.CONCLUSION:The
five-parameter sigmoidal models outperform the established four-parameter
model with high statistical significance. The estimation of essential
PCR parameters such as PCR efficiency, threshold cycles and initial
template fluorescence is more robust and has smaller variance. The
model is implemented in the qpcR package for the freely available
statistical R environment. The package can be downloaded from the
author's homepage.},
doi = {10.1186/1471-2105-9-221},
issn = {1471-2105},
pubmedid = {18445269},
url = {http://www.biomedcentral.com/1471-2105/9/221}
}
@ARTICLE{Spiess2007,
author = {Spiess, Andrej-Nikolai and Feig, Caroline and Schulze, Wolfgang and
Chalmel, Frederic and Cappallo-Obermann, Heike and Primig, Michael
and Kirchhoff, Christiane},
title = {Cross-platform gene expression signature of human spermatogenic failure
reveals inflammatory-like response},
journal = {Hum. Reprod.},
year = {2007},
volume = {22},
pages = {2936--2946},
number = {11},
month = nov,
abstract = {BACKGROUNDThe molecular basis of human testicular dysfunction is largely
unknown. Global gene expression profiling of testicular biopsies
might reveal an expression signature of spermatogenic failure in
azoospermic men. METHODSSixty-nine individual testicular biopsy samples
were analysed on two microarray platforms; selected genes were validated
by quantitative real-time PCR and immunohistochemistry. RESULTSA
minimum of 188 transcripts were significantly increased on both platforms.
Their levels increased with the severity of spermatogenic damage
and reached maximum levels in samples with Sertoli-cell-only appearance,
pointing to genes expressed in somatic testicular cells. Over-represented
functional annotation terms were steroid metabolism, innate defence
and immune response, focal adhesion, antigen processing and presentation
and mitogen-activated protein kinase K signalling pathway. For a
considerable proportion of genes included in the expression signature,
individual transcript levels were in keeping with the individual
mast cell numbers of the biopsies. When tested on three disparate
microarray data sets, the gene expression signature was able to clearly
distinguish normal from defective spermatogenesis. More than 90%
of biopsy samples clustered correctly into the corresponding category,
emphasizing the robustness of our data. CONCLUSIONSA gene expression
signature of human spermatogenic failure was revealed which comprised
well-studied examples of inflammation-related genes also increased
in other pathologies, including autoimmune diseases.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/22/11/2936}
}
@ARTICLE{Spijker2010,
author = {Spijker, Sabine and Zanten, Jeroen S. Van and Jong, Simone De and
Penninx, Brenda W.J.H. and van Dyck, Richard and Zitman, Frans G.
and Smit, Jan H. and Ylstra, Bauke and Smit, August B. and Hoogendijk,
Witte J.G.},
title = {Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive
Disorder},
journal = {Biol Psychiatry},
year = {2010},
volume = {68},
pages = {179--186},
number = {2},
month = jul,
abstract = {Major depressive disorder (MDD) is a moderately heritable disorder
with a high lifetime prevalence. At present, laboratory blood tests
to support MDD diagnosis are not available. We used a classifier
approach on blood gene expression profiles of a unique set of unmedicated
subjects (MDD patients and control subjects) to select genes with
expression predictive for disease status. To reveal blood gene expression
changes related to major depressive disorder-disease, we applied
a powerful ex vivo stimulus to the blood: incubation with lipopolysaccharide
(LPS; 10 ng/mL blood). Based on LPS-stimulated blood gene expression
using whole-genome microarrays (primary cohort; 21 MDD patients,
21 healthy control subjects), we identified a set of genes (CAPRIN1,
CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular
signature of MDD. These findings were validated using an independent
quantitative polymerase chain reaction method (primary cohort, p
= .007). The difference between depressive patients and control subjects
was confirmed (p = .019) in a replication cohort of 13 MDD patients
and 14 control subjects. The MDD signature score comprised expression
levels of seven genes could discriminate depressive patients from
control subjects with sensitivity of 76.9% and specificity of 71.8%.
We have shown for the first time that molecular analysis of stimulated
blood cells can be used as an endophenotype for MDD diagnosis, which
is a milestone in establishing biomarkers for neuropsychiatric disorders
with moderate heritability in general. Our results may provide a
new entry point for following and predicting treatment outcome, as
well as prediction of severity and recurrence of major depressive
disorder.},
issn = {0006-3223},
keywords = {Biomarker, genomics, LPS challenge, major depressive disorder, microarray,
real-time quantitative polymerase chain reaction},
publisher = {Elsevier,},
refid = {S0006-3223(10)00246-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0006322310002465?showall=true}
}
@ARTICLE{Spiliotopoulos2009,
author = {Spiliotopoulos, D. and Goffredo, D. and Conti, L. and Di Febo, F.
and Biella, G. and Toselli, M. and Cattaneo, E.},
title = {An optimized experimental strategy for efficient conversion of embryonic
stem (ES)-derived mouse neural stem (NS) cells into a nearly homogeneous
mature neuronal population},
journal = {Neurobiology of Disease},
year = {2009},
volume = {34},
pages = {320--331},
number = {2},
month = may,
abstract = {NS cells are a homogeneous population of neural stem cells which were
previously derived from embryonic stem cells as well as from the
fetal and adult brain. Our previous reports have described a 21 day
long neuronal differentiation protocol able to reproducibly convert
adult SVZ-derived NS (aNS) cells into a population composed of 65%
mature neurons and 35% glial cells. Here we have developed a different
procedure specifically applicable to ES-derived NS cells in order
to fully explore their neurogenic capacity. Differently from the
aNS differentiation procedure, optimized neuronal output from ES-derived
NS cells requires replating of the cells on appropriate substrates
followed by sequential exposure to modified media. In these conditions,
ES-derived NS cells differentiate into neurons with a barely appreciable
quota of astrocytes and occasional oligodendrocytes. In particular,
21 days after the beginning of the treatment, 85% of the cells has
differentiated into molecularly and electrophysiologically mature
neurons belonging to the GABAergic lineage. The procedure, which
is applicable with no considerable differences to different ES-derived
NS cell lines and to NS cells at different passages, opens to the
possibility of molecular and biochemical studies on close-to-uniform
stem cell derived neurons.},
issn = {0969-9961},
keywords = {Neural differentiation, Neural stem cell, NS cells, In vitro differentiation,
Neurons},
url = {http://www.sciencedirect.com/science/article/B6WNK-4VNK67S-1/2/b9ae5e0efb05ac020e5e7e857765c547}
}
@ARTICLE{Spillman2010,
author = {Spillman, Monique A. and Manning, Nicole G. and Dye, Wendy W. and
Sartorius, Carol A. and Post, Miriam D. and Harrell, Joshua Chuck
and Jacobsen, Britta M. and Horwitz, Kathryn B.},
title = {Tissue-Specific Pathways for Estrogen Regulation of Ovarian Cancer
Growth and Metastasis},
journal = {Cancer Res.},
year = {2010},
volume = {70},
pages = {8927--8936},
number = {21},
month = nov,
abstract = {Menopausal estrogen (E2) replacement therapy increases the risk of
estrogen receptor (ER)-positive epithelial ovarian cancers (EOC).
Whether E2 is tumorigenic or promotes expansion of undiagnosed preexisting
disease is unknown. To determine E2 effects on tumor promotion, we
developed an intraperitoneal mouse xenograft model using ZsGreen
fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was
quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly
increased size, induced progesterone receptors, and promoted lymph
node metastasis, confirming that ERs are functional and foster aggressiveness.
Laser-captured human EOC cells from ER- and ER+ xenografted tumors
were profiled for expression of E2-regulated genes. Three classes
of E2-regulated EOC genes were defined, but <10% were shared with
E2-regulated breast cancer genes. Because breast cancer selective
ER modulators (SERM) are therapeutically ineffective in EOC, we suggest
that our EOC-specific E2-regulated genes can assist pharmacologic
discovery of ovarian-targeted SERM. Cancer Res; 70(21); 8927-36.
(C)2010 AACR.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/70/21/8927}
}
@ARTICLE{Spin2011,
author = {Spin, Joshua M. and Hsu, Mark and Azuma, Junya and Tedesco, Maureen
M. and Deng, Alicia and Dyer, Justin S. and Maegdefessel, Lars and
Dalman, Ronald L. and Tsao, Philip S.},
title = {Transcriptional profiling and network analysis of the murine angiotensin
II-induced abdominal aortic aneurysm},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {993-1003},
number = {17},
abstract = {We sought to characterize temporal gene expression changes in the
murine angiotensin II (ANG II)-ApoE-/- model of abdominal aortic
aneurysm (AAA). Aortic ultrasound measurements were obtained over
the 28-day time-course. Harvested suprarenal aortic segments were
evaluated with whole genome expression profiling at 7, 14, and 28
days using the Agilent Whole Mouse Genome microarray platform and
Statistical Analysis of Microarrays at a false discovery rate of
<1%. A group of angiotensin-treated mice experienced contained rupture
(CR) within 7 days and were analyzed separately. Progressive aortic
dilatation occurred throughout the treatment period. However, the
numerous early expression differences between ANG II-treated and
control were not sustained over time. Ontologic analysis revealed
widespread upregulation of inflammatory, immune, and matrix remodeling
genes with ANG II treatment, among other pathways such as apoptosis,
cell cycling, angiogenesis, and p53 signaling. CR aneurysms displayed
significant decreases in TGF-{beta}/BMP-pathway signaling, MAPK signaling,
and ErbB signaling genes vs. non-CR/ANG II-treated samples. We also
performed literature-based network analysis, extracting numerous
highly interconnected genes associated with aneurysm development
such as Spp1, Myd88, Adam17 and Lox. 1) ANG II treatment induces
extensive early differential expression changes involving abundant
signaling pathways in the suprarenal abdominal aorta, particularly
wide-ranging increases in inflammatory genes with aneurysm development.
2) These gene expression changes appear to dissipate with time despite
continued growth, suggesting that early changes in gene expression
influence disease progression in this AAA model, and that the aortic
tissue adapts to prolonged ANG II infusion. 3) Network analysis identified
nexus genes that may constitute aneurysm biomarkers or therapeutic
targets.},
doi = {10.1152/physiolgenomics.00044.2011},
eprint = {http://physiolgenomics.physiology.org/cgi/reprint/43/17/993.pdf},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/17/993}
}
@ARTICLE{Spink2009,
author = {Spink, Barbara C. and Bennett, James A. and Pentecost, Brian T. and
Lostritto, Nicole and Englert, Neal A. and Benn, Geoffrey K. and
Goodenough, Angela K. and Turesky, Robert J. and Spink, David C.},
title = {Long-term estrogen exposure promotes carcinogen bioactivation, induces
persistent changes in gene expression, and enhances the tumorigenicity
of MCF-7 human breast cancer cells},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {240},
pages = {355--366},
number = {3},
month = nov,
abstract = {The cumulative exposure to estrogens is an important determinant in
the risk of breast cancer, yet the full range of mechanisms involving
estrogens in the genesis and progression of breast cancer remains
a subject of debate. Interactions of estrogens and environmental
toxicants have received attention as putative factors contributing
to carcinogenesis. Mechanistic studies have demonstrated interactions
between estrogen receptor [alpha] (ER[alpha]) and the aryl hydrocarbon
receptor (AhR), with consequences on the genes that they regulate.
Many studies of ER[alpha] and AhR-mediated effects and crosstalk
between them have focused on the initial molecular events. In this
study, we investigated ER[alpha]- and AhR-mediated effects in long-term
estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were
obtained by continuous culturing for at least 12 weeks in medium
supplemented with 1 nM of 17[beta]-estradiol (E2). With these LTEE
cells and with parallel control cells cultured without E2 supplementation,
we performed an extensive study of cytochrome P450 (CYP) induction,
carcinogen bioactivation, global gene expression, and tumorigenicity
in immunocompromised mice. We found that LTEE cells, in comparison
with control cells, had higher levels of AhR mRNA and protein, greater
responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold
higher initial level of benzo(a)pyrene-DNA adducts as determined
by liquid chromatography tandem mass spectrometry, marked differences
in the expression of numerous genes, and a higher rate of E2-dependent
tumor growth as xenografts. These studies indicate that LTEE causes
adaptive responses in MCF-7 cells, which may reflect processes that
contribute to the overall carcinogenic effect of E2.},
issn = {0041-008X},
keywords = {Breast cancer, MCF-7 cells, Long-term estrogen exposure, Benzo(a)pyrene,
DNA adducts},
url = {http://www.sciencedirect.com/science/article/B6WXH-4WSY48W-1/2/df29cb9792a79a6c97e8a11f0e473fbe}
}
@ARTICLE{Spinnewyn2011,
author = {Spinnewyn, Brigitte and Mautino, Gisele and Marin, Jean-Gregoire
and Rocher, Marie Noëlle and Grandoulier, Anne Sophie and Ferrandis,
Eric and Auguet, Michel and Chabrier, Pierre-Etienne},
title = {BN82451 attenuates l-dopa-induced dyskinesia in 6-OHDA-lesioned rat
model of Parkinson's disease},
journal = {Neuropharmacology},
year = {2011},
volume = {60},
pages = {692--700},
number = {4},
month = mar,
abstract = {The development of l-dopa-induced dyskinesia (LID) remains a major
problem in the long-term treatment of Parkinson's disease (PD). This
study aimed to assess the effect of the multitargeting molecule BN82451
on LID and to measure striatal mRNA expression of several genes in
a rat model of PD. Rats were administered two unilateral injections
of 6-OHDA in the striatum. After four weeks, the animals started
a chronic daily treatment with increasing doses of l-dopa over a
further four-week period. Over the course of l-dopa treatment, the
rats developed abnormal involuntary movements (AIMs) classified as
locomotive, axial, orolingual and forelimb dyskinesia. In animals
rendered dyskinetic by l-dopa, administration of BN82451 at doses
ranging from 1 to 10 mg/kg p.o. attenuated the severity of fully-established
AIMs in a dose-related manner. This anti-dyskinetic effect could
be achieved with lower doses of BN82451 administered sub chronically
vs. acute single treatment. The improvement of AIMs is not due to
a reduction in the general motor activity of dyskinetic rats. BN82451
treatment significantly reversed the overexpression of c-Fos, FosB
and Arc mRNA associated with the dyskinesiogenic action of l-dopa.
A significant correlation between the degree of overexpression of
c-Fos, FosB and Arc mRNA and the dyskinesiogenic action of l-dopa
was observed. The data demonstrate that BN82451 effectively attenuates
LID and the associated molecular alterations in an animal model of
PD and may represent a treatment option for managing dyskinesia.},
issn = {0028-3908},
keywords = {BN82451, Dyskinesia, l-dopa, FosB, c-Fos, 6-OHDA},
url = {http://www.sciencedirect.com/science/article/pii/S0028390810003187}
}
@ARTICLE{Spinola2010,
author = {Spinola, Stanley M. and Fortney, Kate R. and Baker, Beth and Janowicz,
Diane M. and Zwickl, Beth and Katz, Barry P. and Blick, Robert J.
and Munson, Robert S., Jr.},
title = {Activation of the CpxRA System by Deletion of cpxA Impairs the Ability
of Haemophilus ducreyi To Infect Humans},
journal = {Infect. Immun.},
year = {2010},
volume = {78},
pages = {3898--3904},
number = {9},
month = sep,
abstract = {Haemophilus ducreyi must adapt to the environment of the human host
to establish and maintain infection in the skin. Bacteria generally
utilize stress response systems, such as the CpxRA two-component
system, to adapt to hostile environments. CpxRA is the only obvious
two-component system contained in the H. ducreyi genome and negatively
regulates the lspB-lspA2 operon, which encodes proteins that enable
the organism to resist phagocytosis. We constructed an unmarked,
in-frame H. ducreyi cpxA deletion mutant, 35000HP{Delta}cpxA. In
human inoculation experiments, 35000HP{Delta}cpxA formed papules
at a rate and size that were significantly less than its parent and
was unable to form pustules compared to the parent. CpxA usually
has kinase and phosphatase activities for CpxR, and the deletion
of CpxA leads to the accumulation of activated CpxR due to the loss
of phosphatase activity and the ability of CpxR to accept phosphate
groups from other donors. Using a reporter construct, the lspB-lspA2
promoter was downregulated in 35000HP{Delta}cpxA, confirming that
CpxR was activated. Deletion of cpxA downregulated DsrA, the major
determinant of serum resistance in the organism, causing the mutant
to become serum susceptible. Complementation in trans restored parental
phenotypes. 35000HP{Delta}cpxA is the first H. ducreyi mutant that
is impaired in its ability to form both papules and pustules in humans.
Since a major function of CpxRA is to control the flow of protein
traffic across the periplasm, uncontrolled activation of this system
likely causes dysregulated expression of multiple virulence determinants
and cripples the ability of the organism to adapt to the host.},
url = {http://iai.asm.org/cgi/content/abstract/78/9/3898}
}
@ARTICLE{Spitzner2010,
author = {Spitzner, Melanie and Emons, Georg and Kramer, Frank and Gaedcke,
Jochen and Rave-Fränk, Margret and Scharf, Jens-Gerd and Burfeind,
Peter and Becker, Heinz and Beissbarth, Tim and Ghadimi, B. Michael
and Ried, Thomas and Grade, Marian},
title = {A Gene Expression Signature for Chemoradiosensitivity of Colorectal
Cancer Cells},
journal = {Int J Radiat Oncol Biol Phys},
year = {2010},
volume = {78},
pages = {1184--1192},
number = {4},
month = nov,
abstract = {The standard treatment of patients with locally advanced rectal cancers
comprises preoperative 5-fluorouracil–based chemoradiotherapy followed
by standardized surgery. However, tumor response to multimodal treatment
has varied greatly, ranging from complete resistance to complete
pathologic regression. The prediction of the response is, therefore,
an important clinical need. To establish in vitro models for studying
the molecular basis of this heterogeneous tumor response, we exposed
12 colorectal cancer cell lines to 3 μM of 5-fluorouracil and 2
Gy of radiation. The differences in treatment sensitivity were then
correlated with the pretherapeutic gene expression profiles of these
cell lines. We observed a heterogeneous response, with surviving
fractions ranging from 0.28 to 0.81, closely recapitulating clinical
reality. Using a linear model analysis, we identified 4,796 features
whose expression levels correlated significantly with the sensitivity
to chemoradiotherapy (Q <.05), including many genes involved in the
mitogen-activated protein kinase signaling pathway or cell cycle
genes. These data have suggested a potential relevance of the insulin
and Wnt signaling pathways for treatment response, and we identified
STAT3, RASSF1, DOK3, and ERBB2 as potential therapeutic targets.
The microarray measurements were independently validated for a subset
of these genes using real-time polymerase chain reactions. We are
the first to report a gene expression signature for the in vitro
chemoradiosensitivity of colorectal cancer cells. We anticipate that
this analysis will unveil molecular biomarkers predictive of the
response of rectal cancers to chemoradiotherapy and enable the identification
of genes that could serve as targets to sensitize a priori resistant
primary tumors.},
issn = {0360-3016},
keywords = {Colorectal cancer, chemoradiotherapy, response, resistance, gene expression
profiling},
publisher = {Elsevier Science Inc.},
refid = {S0360-3016(10)00872-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0360301610008722?showall=true}
}
@ARTICLE{Spivey2011,
author = {Spivey, Vicky L. and Molle, Virginie and Whalan, Rachael H. and Rodgers,
Angela and Leiba, Jade and Stach, Lasse and Walker, K. Barry and
Smerdon, Stephen J. and Buxton, Roger S.},
title = {Forkhead-associated (FHA) Domain Containing ABC Transporter Rv1747
Is Positively Regulated by Ser/Thr Phosphorylation in Mycobacterium
tuberculosis},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {26198-26209},
number = {29},
abstract = {One major signaling method employed by Mycobacterium tuberculosis,
the causative agent of tuberculosis, is through reversible phosphorylation
of proteins mediated by protein kinases and phosphatases. This study
concerns one of these enzymes, the serine/threonine protein kinase
PknF, that is encoded in an operon with Rv1747, an ABC transporter
that is necessary for growth of M. tuberculosis in vivo and contains
two forkhead-associated (FHA) domains. FHA domains are phosphopeptide
recognition motifs that specifically recognize phosphothreonine-containing
epitopes. Experiments to determine how PknF regulates the function
of Rv1747 demonstrated that phosphorylation occurs on two specific
threonine residues, Thr-150 and Thr-208. To determine the in vivo
consequences of phosphorylation, infection experiments were performed
in bone marrow-derived macrophages and in mice using threonine-to-alanine
mutants of Rv1747 that prevent specific phosphorylation and revealed
that phosphorylation positively modulates Rv1747 function in vivo.
The role of the FHA domains in this regulation was further demonstrated
by isothermal titration calorimetry, using peptides containing both
phosphothreonine residues. FHA-1 domain mutation resulted in attenuation
in macrophages highlighting the critical role of this domain in Rv1747
function. A mutant deleted for pknF did not, however, have a growth
phenotype in an infection, suggesting that other kinases can fulfill
its role when it is absent. This study provides the first information
on the molecular mechanism(s) regulating Rv1747 through PknF-dependent
phosphorylation but also indicates that phosphorylation activates
Rv1747, which may have important consequences in regulating growth
of M. tuberculosis.},
doi = {10.1074/jbc.M111.246132},
eprint = {http://www.jbc.org/cgi/reprint/286/29/26198.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/29/26198}
}
@ARTICLE{Sponheim2010,
author = {Sponheim, Jon and Pollheimer, Jurgen and Olsen, Trine and Balogh,
Johanna and Hammarstrom, Clara and Loos, Tamara and Kasprzycka, Monika
and Sorensen, Dag Reidar and Nilsen, Hogne Roed and Kuchler, Axel
M. and Vatn, Morten H. and Haraldsen, Guttorm},
title = {Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially
Expressed in Ulceration-Associated Myofibroblasts},
journal = {Am. J. Pathol.},
year = {2010},
volume = {177},
pages = {2804--2815},
number = {6},
month = dec,
abstract = {Interleukin-33 (IL-33) is a novel member of the interleukin-1 family
that induces mucosal pathology in vivo and may drive fibrosis development
and angiogenesis. To address its potential role in inflammatory bowel
disease, we explored its tissue expression in biopsy specimens from
untreated ulcerative colitis patients, observing a 2.6-fold up-regulation
of IL-33 mRNA levels, compared to controls. Immunohistochemical analyses
of surgical specimens showed that a prominent source of IL-33 in
ulcerative colitis lesions were ulceration-associated myofibroblasts
that co-expressed the fibroblast marker heat shock protein 47, platelet-derived
growth factor receptor (PDGFR){beta}, and, in part, the myofibroblast
marker {alpha}-smooth muscle actin (SMA). In contrast, IL-33-positive
myofibroblasts were almost absent near the deep fissures seen in
Crohn's disease. A screen of known and putative activators of IL-33
in cultured fibroblasts revealed that the Toll-like receptor-3 agonist
poly (I:C) was among the strongest inducers of IL-33 and that it
synergized with transforming growth factor-{beta}, a combination
also known to boost myofibroblast differentiation. Experimental wound
healing in rat skin revealed that the de novo induction of IL-33
in pericytes and the possible activation of scattered, tissue-resident
IL-33+PDGFR{beta}+{alpha}SMA- fibroblast-like cells were early events
that preceded the later appearance of IL-33+PDGFR{beta}+{alpha}SMA+
cells. In conclusion, our data point to a novel role for IL-33 in
mucosal healing and wound repair and to an interesting difference
between ulcerative colitis and Crohn's disease.},
comment = {10.2353/ajpath.2010.100378},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/6/2804}
}
@ARTICLE{Sporer2011,
author = {Sporer, Kelly and Tempelman, Robert and Ernst, Catherine and Reed,
Kent and Velleman, Sandra and Strasburg, Gale},
title = {Transcriptional profiling identifies differentially expressed genes
in developing turkey skeletal muscle},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {143},
number = {1},
abstract = {BACKGROUND:Skeletal muscle growth and development from embryo to adult
consists of a series of carefully regulated changes in gene expression.
Understanding these developmental changes in agriculturally important
species is essential to the production of high quality meat products.
For example, consumer demand for lean, inexpensive meat products
has driven the turkey industry to unprecedented production through
intensive genetic selection. However, achievements of increased body
weight and muscle mass have been countered by an increased incidence
of myopathies and meat quality defects. In a previous study, we developed
and validated a turkey skeletal muscle-specific microarray as a tool
for functional genomics studies. The goals of the current study were
to utilize this microarray to elucidate functional pathways of genes
responsible for key events in turkey skeletal muscle development
and to compare differences in gene expression between two genetic
lines of turkeys. To achieve these goals, skeletal muscle samples
were collected at three critical stages in muscle development: 18d
embryo (hyperplasia), 1d post-hatch (shift from myoblast-mediated
growth to satellite cell-modulated growth by hypertrophy), and 16wk
(market age) from two genetic lines: a randombred control line (RBC2)
maintained without selection pressure, and a line (F) selected from
the RBC2 line for increased 16wk body weight. Array hybridizations
were performed in two experiments: Experiment 1 directly compared
the developmental stages within genetic line, while Experiment 2
directly compared the two lines within each developmental stage.RESULTS:A
total of 3474 genes were differentially expressed (false discovery
rate; FDR < 0.001) by overall effect of development, while 16 genes
were differentially expressed (FDR < 0.10) by overall effect of genetic
line. Ingenuity Pathways Analysis was used to group annotated genes
into networks, functions, and canonical pathways. The expression
of 28 genes involved in extracellular matrix regulation, cell death/apoptosis,
and calcium signaling/muscle function, as well as genes with miscellaneous
function was confirmed by qPCR.CONCLUSIONS:The current study identified
gene pathways and uncovered novel genes important in turkey muscle
growth and development. Future experiments will focus further on
several of these candidate genes and the expression and mechanism
of action of their protein products.},
doi = {10.1186/1471-2164-12-143},
issn = {1471-2164},
pubmedid = {21385442},
url = {http://www.biomedcentral.com/1471-2164/12/143}
}
@ARTICLE{Sporer2008,
author = {Sporer, K.R. Buckham and Xiao, L. and Tempelman, R.J. and Burton,
J.L. and Earley, B. and Crowe, M.A.},
title = {Transportation stress alters the circulating steroid environment
and neutrophil gene expression in beef bulls},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {121},
pages = {300--320},
number = {3-4},
month = feb,
abstract = {Stress and its association with altered immune function and incidence
of respiratory diseases in cattle have lead to concerns over animal
health and welfare during truck transportation. Previously, bulls
subjected to transportation stress displayed altered expression of
candidate neutrophil genes, warranting a broader investigation of
the neutrophil transcriptome and possible associations with fluctuations
in circulating steroid hormones. In the current study, blood was
collected from six Belgian Blue × Friesian bulls at -24, 0, 4.5,
9.75, 14.25, 24, and 48 h relative to initiation of 9 h of truck
transportation. Plasma concentrations of cortisol, dehydroepiandrosterone
(DHEA), progesterone, and testosterone were measured; cortisol:DHEA
ratios were computed. Neutrophil gene expression was monitored by
microarray analysis using bovine immunobiology (BOTL-5) microarrays.
Eighty-eight genes were identified as being differentially expressed
at P < 0.05. Putatively affected genes were grouped into ontological
clusters; those of greatest interest for qRT-PCR validation were
involved in immune response, apoptosis, wound healing, and several
of currently unknown function. Confirmed gene expression changes
supported the dramatic effects of transportation stress on the bovine
neutrophil transcriptome. Temporal correlations between gene expression
profiles and circulating total leukocyte and neutrophil counts were
apparent. However, few relationships between gene expression and
plasma steroid profiles were detected, possibly due to the biological
time-lag between these variables not captured by the blood collection
schedule. Further investigation into the factors underlying neutrophil
gene expression changes and validations at the protein and cell behavior
levels will lead to a better understanding of altered innate immunity
in cattle during transportation stress.},
issn = {0165-2427},
keywords = {Transportation stress, Steroids, Neutrophils, cDNA microarray, Beef
cattle},
url = {http://www.sciencedirect.com/science/article/B6TD5-4PYP6WX-1/2/54c96ad8cdc9242ab50a29d42432d55b}
}
@ARTICLE{Sporer2011a,
author = {Sporer, K. R. B. and Chiang, W. and Tempelman, R. J. and Ernst, C.
W. and Reed, K. M. and Velleman, S. G. and Strasburg, G. M.},
title = {Characterization of a 6K oligonucleotide turkey skeletal muscle microarray},
journal = {Animal Genetics},
year = {2011},
volume = {42},
pages = {75--82},
number = {1},
abstract = {Summary Consumer demand for lean, inexpensive meat products has driven
the domestic turkey (Meleagris gallopavo) industry to unprecedented
production; however, this has coincided with an increase in growth-induced
myopathies and meat quality defects. With the aim of developing a
new tool for the study of turkey growth and development at the muscle
transcriptome level, a 6K oligonucleotide microarray was constructed,
the Turkey Skeletal Muscle Long Oligo (TSKMLO) microarray. Skeletal
muscle samples were collected at three critical stages in muscle
development: 18-day embryo (hyperplasia), 1-day post-hatch (hypertrophy),
and 16-week (market age) from two genetic lines of turkeys: RBC2,
a line maintained without selection pressure, and F, a line selected
from the RBC2 line for increased 16-week body weight. Oligonucleotides
were designed from sequences obtained from skeletal muscle cDNA libraries
from the three developmental stages. Several unique controls, including
mismatch and distance controls and scrambled sequences, were designed
for 30 genes. Quality control hybridizations were completed, confirming
the validity and repeatability of the array. Control features were
evaluated across two larger experiments comparing developmental stage
within genetic line or genetic line within each developmental stage,
totaling 70 arrays. Mismatch and scrambled sequences appeared to
be useful controls of specific hybridization for most genes. In addition,
quantitative real-time RT-PCR confirmed microarray results. This
creation and assessment of the TSKMLO array provides a valuable community
resource for the study of gene expression changes related to turkey
muscle growth and development.},
doi = {10.1111/j.1365-2052.2010.02085.x},
issn = {1365-2052},
keywords = {growth and development, microarray, skeletal muscle, turkey},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2010.02085.x}
}
@ARTICLE{Sporn2011,
author = {Sporn, Judith C. and Hothorn, Torsten and Jung, Barbara},
title = {BARD1 Expression Predicts Outcome in Colon Cancer},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {5451-5462},
number = {16},
abstract = {Purpose: BARD1 is a BRCA1-binding partner with tumor suppressive properties.
Aberrant splice variants of BARD1 have been detected in various cancers,
and it has been postulated that the presence of some splice variants
is cancer specific. This is the first study assessing BARD1 expression
patterns and correlation with clinical outcome in colon cancer. Experimental
Design: We analyzed colon cancer samples for the occurrence of BARD1
splice variants, characterized novel BARD1 splice variants, and quantified
the mRNA expression levels of these isoforms in primary colon cancers
and their corresponding normal tissue. We tested the correlation
of full-length BARD1 protein expression and clinical outcome in primary
colon cancer samples. Results: In addition to the full-length BARD1
mRNA, we now find 19 distinct BARD1 splice variants in colon cancer.
Contrary to previous assumptions, these splice variants also occur
in the adjacent normal colon tissue. Although BARD1 splice variants
account for a considerable amount of BARD1 mRNA in both cancer and
normal colon samples, distinct variants show a cancer-specific regulation
pattern. Consistent with its role as tumor suppressor, we further
find that the expression of the full-length BARD1 protein predicts
outcome in colon cancer and that loss of full-length BARD1 protein
is associated with a poor prognosis (P = 0.0002). Conclusion: Taken
together, this is the first report to suggest that BARD1 regulation
is an important pathway in colon cancer and that the BARD1 full-length
protein may be a useful marker to improve risk stratification in
colon cancer patients. Clin Cancer Res; 17(16); 5451-62. (C)2011
AACR.},
doi = {10.1158/1078-0432.CCR-11-0263},
eprint = {http://clincancerres.aacrjournals.org/cgi/reprint/17/16/5451.pdf},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/16/5451}
}
@ARTICLE{Sposny2011,
author = {Sposny, Alexandra and Schmitt, Christina S. and Hewitt, Philip G.},
title = {Mechanistic Investigation of EMD335823s Hepatotoxicity Using Multiple
Omics Profiling Technologies},
journal = {General, Applied and Systems Toxicology},
year = {2011},
volume = {na},
abstract = {We have used modern omics technologies (including Toxicogenomics,
proteomics, metabonomics and profiling from FFPE tissues) to ascertain
whether a systems biology approach would improve our understanding
of the mechanism of toxicity of a compound.Wistar rats were treated
for up to 14 days with a non-toxic dose (15 mg kg−1) or a high
dose (350 mg kg−1) of a known hepatotoxic compound (EMD 335823),
chosen to ensure significant hepatotoxicity (liver necrosis, fibrosis,
and bile duct necrosis/hyperplasia).Genomics, proteomics, and metabonomics
identified animals with the most severe effects, in good agreement
with pathological findings. Protein expression changes correlated
well with gene expression changes, indicating that EMD 335823 regulated
PPARα signaling. EMD 335823 is an aldose reductase inhibitor resulting
in increased glucose metabolism and alterations in fatty acid metabolism.
These disturbances result in lower energy resources, contributing
to the pathogenesis of liver damage. Proteomics and metabonomics
also showed clear separation of the most severely affected animals,
although the limited numbers of molecules identified could not reveal
the mechanism of toxicity alone.The combination of omics technologies
allowed a more detailed analysis and identification of potential
mechanisms of action, improving the overall understanding of the
compounds toxicity. Additionally, there are indications that a compound-specific
signature was visible earlier, when no histopathological changes
occurred.},
booktitle = {General, Applied and Systems Toxicology},
doi = {10.1002/9780470744307.gat224},
isbn = {9780470744307},
keywords = {cross-omics comparison, genomics, hepatotoxicity, metabonomics, proteomics,
systems toxicology},
publisher = {John Wiley \& Sons, Ltd},
url = {http://onlinelibrary.wiley.com/doi/10.1002/9780470744307.gat224/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+14+Jan+from+10-12+GMT+for+monthly+maintenance}
}
@ARTICLE{Spradling2011,
author = {Spradling, Kimberly and Lumley, Lucille and Robison, Christopher
and Meyerhoff, James and Dillman, James},
title = {Transcriptional responses of the nerve agent-sensitive brain regions
amygdala, hippocampus, piriform cortex, septum, and thalamus following
exposure to the organophosphonate anticholinesterase sarin},
journal = {Journal of Neuroinflammation},
year = {2011},
volume = {8},
pages = {84},
number = {1},
abstract = {BACKGROUND:Although the acute toxicity of organophosphorus nerve agents
is known to result from acetylcholinesterase inhibition, the molecular
mechanisms involved in the development of neuropathology following
nerve agent-induced seizure are not well understood. To help determine
these pathways, we previously used microarray analysis to identify
gene expression changes in the rat piriform cortex, a region of the
rat brain sensitive to nerve agent exposure, over a 24-h time period
following sarin-induced seizure. We found significant differences
in gene expression profiles and identified secondary responses that
potentially lead to brain injury and cell death. To advance our understanding
of the molecular mechanisms involved in sarin-induced toxicity, we
analyzed gene expression changes in four other areas of the rat brain
known to be affected by nerve agent-induced seizure (amygdala, hippocampus,
septum, and thalamus).METHODS:We compared the transcriptional response
of these four brain regions to sarin-induced seizure with the response
previously characterized in the piriform cortex. In this study, rats
were challenged with 1.0 x LD50 sarin and subsequently treated with
atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam.
The four brain regions were collected at 0.25, 1, 3, 6, and 24 h
after seizure onset, and total RNA was processed for microarray analysis.RESULTS:Principal
component analysis identified brain region and time following seizure
onset as major sources of variability within the dataset. Analysis
of variance identified genes significantly changed following sarin-induced
seizure, and gene ontology analysis identified biological pathways,
functions, and networks of genes significantly affected by sarin-induced
seizure over the 24-h time course. Many of the molecular functions
and pathways identified as being most significant across all of the
brain regions were indicative of an inflammatory response. There
were also a number of molecular responses that were unique for each
brain region, with the thalamus having the most distinct response
to nerve agent-induced seizure.CONCLUSIONS:Identifying the molecular
mechanisms involved in sarin-induced neurotoxicity in these sensitive
brain regions will facilitate the development of novel therapeutics
that can potentially provide broad-spectrum protection in five areas
of the central nervous system known to be damaged by nerve agent-induced
seizure.},
doi = {10.1186/1742-2094-8-84},
issn = {1742-2094},
pubmedid = {21777430},
url = {http://www.jneuroinflammation.com/content/8/1/84}
}
@ARTICLE{Springer2012,
author = {Alexander Springer and Klaus Kratochwill and Helga Bergmeister and
Dagmar Csaicsich and Johann Huber and Martin Bilban and Bernd Mayer
and Irmgard Mühlberger and Gabriele Amann and Ernst Horcher and
Christoph Aufricht},
title = {A Combined Transcriptome and Bioinformatics Approach to Unilateral
Ureteral Obstructive Uropathy in the Fetal Sheep Model},
journal = {The Journal of Urology},
year = {2012},
volume = {187},
pages = {751 - 756},
number = {2},
abstract = {Purpose Fetal obstructive uropathy is a leading cause of loss of renal
function. Characterizing the molecular fingerprint of cellular responses
to obstruction in a fetal model of complete unilateral ureteral obstruction
may help elucidate the activated mechanisms and suggest new therapeutic
interventions. Material and Methods Unilateral ureteral obstruction
was created in 3 sheep fetuses at day 60 of gestation. For transcriptome
analysis total RNA was extracted from vital renal biopsies 2 weeks
after intervention from obstructed kidneys and from control kidneys
of untreated twins. cDNA preparation, hybridization to the GeneChip®
Bovine Genome Array and array scanning were done according to manufacturer
protocols. Bioinformatics analysis was used to derive functional
biological processes linked to obstructive uropathy. Quantitative
reverse-transcriptase-polymerase chain reaction and immunohistochemistry
were used to validate microarray results. Results Seven biological
processes were identified as significantly affected by differentially
regulated features that characterize unilateral ureteral obstruction,
namely protein metabolism and modification, other metabolism, neuronal
activity, ligand mediated signaling, amino acid metabolism, coenzyme/prosthetic
group metabolism and rRNA metabolism. Literature mining identified
17 candidate genes previously reported as key in the context of unilateral
ureteral obstruction, related pathological mechanisms or other kidney
diseases. Conclusions Combined transcriptome and bioinformatics analysis
allowed the identification of enriched processes in the fetal sheep
model of unilateral ureteral obstruction that are likely associated
with renal damage but to our knowledge have not been previously identified.
Future clarification of these molecular fingerprints may eventually
provide therapeutic targets and early predictive markers involved
in the pathogenesis of fetal uropathy.},
doi = {10.1016/j.juro.2011.09.148},
issn = {0022-5347},
keywords = {ureter},
url = {http://www.sciencedirect.com/science/article/pii/S0022534711052049}
}
@ARTICLE{Sprogar2008,
author = {Sprogar, Spela and Vaupotic, Tomaz and Cör, Andrej and Drevensek,
Martina and Drevensek, Gorazd},
title = {The endothelin system mediates bone modeling in the late stage of
orthodontic tooth movement in rats},
journal = {Bone},
year = {2008},
volume = {43},
pages = {740--747},
number = {4},
month = oct,
abstract = {The endothelin system is involved in orthodontic tooth movement (OTM).
The aim of the study was to examine the role of ET-1, ETA and ETB
in bone modeling during OTM in rats. Male Wistar rats (n = 62) were
divided into three groups: control animals (n = 10; control group)
without appliance, and two groups of experimental animals, which
were applied a super-elastic closed-coil spring between the first
left maxillary molar and the incisors and were treated daily with
either TBC3214 (n = 10; TBC3214 group) or with saline (n = 42; appliance
only group). TBC3214 is a highly selective antagonist on ETA receptors.
The distance between teeth was measured on days 0 and 42. On days
0, 14, 28 and 42 animals of the appliance only group (n = 8) were
sacrificed and tissue samples were taken. Total RNA and protein contents
were isolated. Gene expression levels of ET-1, ETA and ETB were assessed
by means of relative RT-PCR. Protein levels of ETA and ETB were examined
by immunoblotting. Ten animals of each group were sacrificed on day
42 and tissue samples were prepared for histological analysis. Alveolar
bone volume, osteoblast and osteoclast volume were determined histomorphometrically.
Gene expression levels of ET-1, ETA and ETB varied throughout the
experiment and were significantly up-regulated on day 42 (p < 0.001).
The immunoreactivity of ETA and ETB significantly decreased on day
14 (p < 0.001) and increased on day 28 (p < 0.001). Alveolar bone
volume was significantly higher in the TBC3214 group compared to
the appliance only group (p < 0.001). Osteoclast volume was significantly
lower in the TBC3214 group compared to the appliance only group (p < 0.05).
Gene and protein expression levels of ET-1, ETA and ETB varied significantly
during OTM, suggesting their different roles in the various stages
of OTM. TBC3214 significantly increased alveolar bone volume and
significantly decreased osteoclast volume, indicating that it decreased
bone resorption in stage three of OTM. These data suggest that ET-1
increases osteoclastic bone resorption via ETA in the late stage
of OTM.},
issn = {8756-3282},
keywords = {Bone modeling, Osteoclast, Orthodontic tooth movement, Endothelin
system, Rat},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4SX3P06-1/2/fa880fe10608af4bc45b85a8bc6fe857}
}
@ARTICLE{Sprong2012,
author = {Sprong, H. and Tijsse-Klasen, E. and Langelaar, M. and De Bruin,
A. and Fonville, M. and Gassner, F. and Takken, W. and Van Wieren,
S. and Nijhof, A. and Jongejan, F. and Maassen, C. B. M. and Scholte,
E.-J. and Hovius, J. W. and Emil Hovius, K. and Špitalská, E. and
Van Duynhoven, Y. T.},
title = {Prevalence of Coxiella Burnetii in Ticks After a Large Outbreak of
Q Fever},
journal = {Zoonoses and Public Health},
year = {2012},
volume = {59},
pages = {69--75},
number = {1},
abstract = {Q fever has emerged as an important human and veterinary public health
problem in the Netherlands with major outbreaks in three consecutive
years. Goat farms are probably the prime source from which Coxiella
burnetii have spread throughout the environment, infecting people
living in the vicinity. Coxiella burnetii infection not only spilled
over from animal husbandry to humans but could also have spread to
neighbouring wildlife and pets forming novel reservoirs and consequently
posing another and lingering threat to humans, companion animals
and livestock. In these cases, transmission routes other than airborne
spread of contaminated aerosols may become significant. Therefore,
the role of ticks in the transmission of Coxiella burnetii in the
current situation was investigated. A total of 1891 questing Ixodes
ricinus ticks and 1086 ticks feeding on pets, wildlife and livestock
were tested by a recently developed multiplex Q-PCR. All ticks were
negative, except for a few ticks feeding on a herd of recently vaccinated
sheep. Coxiella-positive ticks were not detected after resampling
this particular herd three months later. Based on these data we conclude
that the current risk of acquiring Q fever from questing ticks in
the Netherlands is negligible. However, for future risk assessments,
it might be relevant to sample more ticks in the vicinity of previously
C. burnetii infected goat farms and to assess whether C. burnetii
can be transmitted transovarially and transstadially in I. ricinus
ticks.},
doi = {10.1111/j.1863-2378.2011.01421.x},
issn = {1863-2378},
keywords = {Ixodes ricinus, ticks, Coxiella burnetii, ruminants, transmission},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1863-2378.2011.01421.x}
}
@ARTICLE{Sprong2010,
author = {Sprong, R.C. and Schonewille, A.J. and van der Meer, R.},
title = {Dietary cheese whey protein protects rats against mild dextran sulfate
sodium-induced colitis: Role of mucin and microbiota},
journal = {Journal of Dairy Science},
year = {2010},
volume = {93},
pages = {1364--1371},
number = {4},
month = apr,
abstract = {Data from the literature suggest that the availability of the amino
acids threonine, cysteine, or both, is limiting for mucin synthesis
under conditions of chronic inflammatory bowel disease. Unlike casein,
cheese whey protein is rich in these amino acids. The protective
effect of cheese whey protein was examined using dextran sulfate
sodium (DSS)-induced inflammation of the large intestine in rats
that were fed a diet containing casein, cheese whey protein, or casein
supplemented with threonine and cysteine. The clinical markers diarrhea
and fecal blood were determined using biochemical assays, and gene
expression of inflammation markers was used to quantify inflammation.
The effect of dairy protein on mucin production was determined by
gene expression of rat mucin 2 (MUC2) and by quantifying fecal mucin
excretion. Fecal lactobacilli and bifidobacteria were determined
using quantitative PCR. Dietary cheese whey protein reduced DSS-induced
gene expression of the inflammation markers interleukin 1[beta],
calprotectin, and inducible nitric oxide synthase, and diminished
the clinical symptoms diarrhea and fecal blood loss. Moreover, cheese
whey protein increased fecal mucin secretion without affecting gene
expression of MUC2, suggesting enhanced mucin synthesis. In addition,
cheese whey protein increased fecal lactobacilli and bifidobacteria
counts. Supplementation of threonine and cysteine showed comparable
effects. In conclusion, cheese whey protein protected rats against
DSS-induced gut inflammation. This can most likely be explained by
its threonine and cysteine content. Protection can be the result
of both the stimulation of intestinal mucin synthesis and modification
of microflora composition.},
issn = {0022-0302},
keywords = {colitis, mucin, microbiota, cheese whey protein},
url = {http://www.sciencedirect.com/science/article/B9887-4YR8NJ3-8/2/f7d1c9223423ff4fff45f3da6e699cc7}
}
@ARTICLE{Spugnini2006,
author = {Spugnini, Enrico P. and Cardillo, Irene and Verdina, Alessandra and
Crispi, Stefania and Saviozzi, Silvia and Calogero, Raffaele and
Nebbioso, Angela and Altucci, Lucia and Cortese, Giancarlo and Galati,
Rossella and Chien, Jeremy and Shridhar, Viji and Vincenzi, Bruno
and Citro, Gennaro and Cognetti, Francesco and Sacchi, Ada and Baldi,
Alfonso},
title = {Piroxicam and Cisplatin in a Mouse Model of Peritoneal Mesothelioma},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {6133--6143},
number = {20},
month = oct,
abstract = {Purpose: The aim of the present study was to evaluate the effects
of piroxicam, a widely used nonsteroidal anti-inflammatory drug,
alone and in combination with cisplatin (CDDP), on cell growth of
mesothelioma cells. Experimental Design: Cell proliferation, cell
cycle analysis, and microarray technology were done on MSTO-211H
and NCI-H2452 cells treated with piroxicam. Moreover, the effects
of piroxicam and CDDP on tumor growth and survival of mouse xenograft
models of mesothelioma were determined. Results: Piroxicam treatment
of MSTO-211H and NCI-H2452 cells resulted in a significant inhibition
of proliferation. Cell cycle analysis revealed that there was an
increase in the rate of apoptosis in MSTO-211H cells and an increase
in the cells accumulating in G2-M in NCI-H2452. Moreover, a marked
tumor growth inhibition and an extended survival of mice treated
with a combination of piroxicam and CDDP in MSTO-211H cell-induced
peritoneal mesotheliomas was observed. Last, GeneChip array analysis
of MSTO-211H mesothelioma cell line revealed that piroxicam treatment
caused up-regulation of metabolic pathway-associated genes and down-regulation
of genes related to RNA processing apparatus. Of note, epidermal
growth factor receptor, one of the new biological targets of chemotherapy
for mesothelioma, was down-regulated and HtrA1, a serine protease
recently shown to be an endogenous mediator of CDDP cytotoxicity,
was up-regulated following piroxicam treatment both in vitro and
in vivo. Conclusion: These data suggest that piroxicam sensitizes
mesothelioma cells to CDDP-induced cytotoxicity by modulating the
expression of several target genes. Therefore, piroxicam in combination
with CDDP might potentially be useful in the treatment of patients
with mesothelioma.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/20/6133}
}
@ARTICLE{Sreenivasulu2008,
author = {Sreenivasulu, Nese and Usadel, Bjorn and Winter, Andreas and Radchuk,
Volodymyr and Scholz, Uwe and Stein, Nils and Weschke, Winfriede
and Strickert, Marc and Close, Timothy J. and Stitt, Mark and Graner,
Andreas and Wobus, Ulrich},
title = {Barley Grain Maturation and Germination: Metabolic Pathway and Regulatory
Network Commonalities and Differences Highlighted by New MapMan/PageMan
Profiling Tools},
journal = {Plant Physiology},
year = {2008},
volume = {146},
pages = {1738--1758},
number = {4},
month = apr,
abstract = {Plant seeds prepare for germination already during seed maturation.
We performed a detailed transcriptome analysis of barley (Hordeum
vulgare) grain maturation, desiccation, and germination in two tissue
fractions (starchy endosperm/aleurone and embryo/scutellum) using
the Affymetrix Barley1 GeneChip. To aid data evaluation, Arabidopsis
thaliana MapMan and PageMan tools were adapted to barley. The analyses
allow a number of conclusions: (1) Cluster analysis revealed a smooth
transition in transcription programs between late seed maturation
and germination within embryo tissues, but not in the endosperm/aleurone.
(2) More than 12,000 transcripts are stored in the embryo of dry
barley grains, many of which are presumably activated during germination.
(3) Transcriptional activation of storage reserve mobilization events
occurs at an early stage of germination, well before radicle protrusion.
(4) Key genes of gibberellin (GA) biosynthesis are already active
during grain maturation at a time when abscisic acid peaks suggesting
the formation of an endogenous store of GA in the aleurone. This
GA probably acts later during germination in addition to newly synthesized
GA. (5) Beside the well-known role of GA in gene activation during
germination spatiotemporal expression data and cis-element searches
in homologous rice promoters confirm an equally important gene-activating
role of abscisic acid during this developmental period. The respective
regulatory webs are linked to auxin and ethylene controlled networks.
In summary, new bioinformatics PageMan and MapMan tools developed
in barley have been successfully used to investigate in detail the
transcriptome relationships between seed maturation and germination
in an important crop plant.},
url = {http://www.plantphysiol.org/cgi/content/abstract/146/4/1738}
}
@ARTICLE{Sriburi2007,
author = {Sriburi, Rungtawan and Bommiasamy, Hemamalini and Buldak, Gerald
L. and Robbins, Gregory R. and Frank, Matthew and Jackowski, Suzanne
and Brewer, Joseph W.},
title = {Coordinate Regulation of Phospholipid Biosynthesis and Secretory
Pathway Gene Expression in XBP-1(S)-induced Endoplasmic Reticulum
Biogenesis},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {7024--7034},
number = {10},
month = mar,
abstract = {Development of the expansive endoplasmic reticulum (ER) present in
specialized secretory cell types requires X-box-binding protein-1
(Xbp-1). Enforced expression of XBP-1(S), a transcriptional activator
generated by unfolded protein response-mediated splicing of Xbp-1
mRNA, is sufficient to induce proliferation of rough ER. We previously
showed that XBP-1(S)-induced ER biogenesis in fibroblasts correlates
with increased production of phosphatidylcholine (PtdCho), the primary
phospholipid of the ER membrane, and enhanced activities of the choline
cytidylyltransferase (CCT) and cholinephosphotransferase enzymes
in the cytidine diphosphocholine (CDP-choline) pathway of PtdCho
biosynthesis. Here, we report that the level and synthesis of CCT,
the rate-limiting enzyme in the CDP-choline pathway, is elevated
in fibroblasts overexpressing XBP-1(S). Furthermore, overexpression
experiments demonstrated that raising the activity of CCT, but not
cholinephosphotransferase, is sufficient to augment PtdCho biosynthesis
in fibroblasts, indicating that XBP-1(S) increases the output of
the CDP-choline pathway primarily via its effects on CCT. Finally,
fibroblasts overexpressing CCT up-regulated PtdCho synthesis to a
level similar to that in XBP-1(S)-transduced cells but exhibited
only a small increase in rough ER and no induction of secretory pathway
genes. The more robust XBP-1(S)-induced ER expansion was accompanied
by induction of a wide array of genes encoding proteins that function
either in the ER or at other steps in the secretory pathway. We propose
that XBP-1(S) regulates ER abundance by coordinately increasing the
supply of membrane phospholipids and ER proteins, the key ingredients
for ER biogenesis.},
url = {http://www.jbc.org/cgi/content/abstract/282/10/7024}
}
@ARTICLE{Sridhar2009,
author = {Sridhar, Kunju and Ross, Douglas T. and Tibshirani, Robert and Butte,
Atul J. and Greenberg, Peter L.},
title = {Relationship of differential gene expression profiles in CD34+ myelodysplastic
syndrome marrow cells to disease subtype and progression},
journal = {Blood},
year = {2009},
volume = {114},
pages = {4847--4858},
number = {23},
month = nov,
abstract = {Microarray analysis with 40 000 cDNA gene chip arrays determined differential
gene expression profiles (GEPs) in CD34+ marrow cells from myelodysplastic
syndrome (MDS) patients compared with healthy persons. Using focused
bioinformatics analyses, we found 1175 genes significantly differentially
expressed by MDS versus normal, requiring a minimum of 39 genes to
separately classify these patients. Major GEP differences were demonstrated
between healthy and MDS patients and between several MDS subgroups:
(1) those whose disease remained stable and those who subsequently
transformed (tMDS) to acute myeloid leukemia; (2) between del(5q)
and other MDS patients. A 6-gene "poor risk" signature was defined,
which was associated with acute myeloid leukemia transformation and
provided additive prognostic information for International Prognostic
Scoring System Intermediate-1 patients. Overexpression of genes generating
ribosomal proteins and for other signaling pathways was demonstrated
in the tMDS patients. Comparison of del(5q) with the remaining MDS
patients showed 1924 differentially expressed genes, with underexpression
of 1014 genes, 11 of which were within the 5q31-32 commonly deleted
region. These data demonstrated (1) GEPs distinguishing MDS patients
from healthy and between those with differing clinical outcomes (tMDS
vs those whose disease remained stable) and cytogenetics [eg, del(5q)];
and (2) molecular criteria refining prognostic categorization and
associated biologic processes in MDS.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/23/4847}
}
@ARTICLE{Srikhanta2005,
author = {Srikhanta, Yogitha N. and Maguire, Tina L. and Stacey, Katryn J.
and Grimmond, Sean M. and Jennings, Michael P.},
title = {The phasevarion: A genetic system controlling coordinated, random
switching of expression of multiple genes},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {5547--5551},
number = {15},
month = apr,
abstract = {Several host-adapted bacterial pathogens contain methyltransferases
associated with type III restriction-modification (R-M) systems that
are subject to reversible, high-frequency on/off switching of expression
(phase variation). To investigate the role of phase-variable expression
of R-M systems, we made a mutant strain lacking the methyltransferase
(mod) associated with a type III R-M system of Haemophilus influenzae
and analyzed its phenotype. By microarray analysis, we identified
a number of genes that were either up- or down-regulated in the mod
mutant strain. This system reports the coordinated random switching
of a set of genes in a bacterial pathogen and may represent a widely
used mechanism.},
url = {http://www.pnas.org/cgi/content/abstract/102/15/5547}
}
@ARTICLE{Sripichai2009,
author = {Sripichai, Orapan and Kiefer, Christine M. and Bhanu, Natarajan V.
and Tanno, Toshihiko and Noh, Seung-Jae and Goh, Sung-Ho and Russell,
J. Eric and Rognerud, Cheryl L. and Ou, Ching-Nan and Oneal, Patricia
A. and Meier, Emily R. and Gantt, Nicole M. and Byrnes, Colleen and
Lee, Y. Terry and Dean, Ann and Miller, Jeffery L.},
title = {Cytokine-mediated increases in fetal hemoglobin are associated with
globin gene histone modification and transcription factor reprogramming},
journal = {Blood},
year = {2009},
volume = {114},
pages = {2299--2306},
number = {11},
month = sep,
abstract = {Therapeutic regulation of globin genes is a primary goal of translational
research aimed toward hemoglobinopathies. Signal transduction was
used to identify chromatin modifications and transcription factor
expression patterns that are associated with globin gene regulation.
Histone modification and transcriptome profiling were performed using
adult primary CD34+ cells cultured with cytokine combinations that
produced low versus high levels of gamma-globin mRNA and fetal hemoglobin
(HbF). Embryonic, fetal, and adult globin transcript and protein
expression patterns were determined for comparison. Chromatin immunoprecipitation
assays revealed RNA polymerase II occupancy and histone tail modifications
consistent with transcriptional activation only in the high-HbF culture
condition. Transcriptome profiling studies demonstrated reproducible
changes in expression of nuclear transcription factors associated
with high HbF. Among the 13 genes that demonstrated differential
transcript levels, 8 demonstrated nuclear protein expression levels
that were significantly changed by cytokine signal transduction.
Five of the 8 genes are recognized regulators of erythropoiesis or
globin genes (MAFF, ID2, HHEX, SOX6, and EGR1). Thus, cytokine-mediated
signal transduction in adult erythroid cells causes significant changes
in the pattern of globin gene and protein expression that are associated
with distinct histone modifications as well as nuclear reprogramming
of erythroid transcription factors.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/11/2299}
}
@ARTICLE{Sriraman2010,
author = {Sriraman, Venkataraman and Sinha, Mala and Richards, JoAnne S.},
title = {Progesterone Receptor-Induced Gene Expression in Primary Mouse Granulosa
Cell Cultures},
journal = {Biol Reprod},
year = {2010},
volume = {82},
pages = {402--412},
number = {2},
month = feb,
abstract = {The progesterone receptor (PGR) is induced by luteinizing hormone
(LH) in granulosa cells of preovulatory follicles, and the PGR-A
isoform is essential for ovulation based on the phenotypes of Pgr
isoform-specific knockout mice. Although several genes regulated
by PGR-A in vivo have been identified, whether these genes are primary
targets of PGR-A or if their expression also depends on other signaling
molecules that are induced by the LH surge has not been resolved.
Therefore, to identify genes that are either induced or repressed
by PGR in the absence of LH-mediated signaling cascades, we infected
primary cultures of mouse granulosa cells with either PGR-A or PGR-B
adenoviral vectors without or with R-5020 as a PGR ligand. Total
RNA was extracted from infected cells at 16 h and analyzed by Affymetrix
Mouse 430 2.0 microarrays. PGR-A in the presence or absence of ligand
significantly induced approximately 50 genes 2-fold or more (local
pooled error test at P [≤] 0.01). Fewer and different genes were
induced by PGR-B in the absence of ligand. Edn1, Apoa1, and Cited1
were primarily regulated by PGR-A as verified by additional RT-PCR
analyses, suppression by the PGR antagonist RU486, and the lack of
induction by protein kinase A, protein kinase C, or epidermal growth
factor (EGF)-like factors pathways. PGR regulation of these genes
was confirmed further by gene expression analyses in hormonally primed
Pgr mutant mouse ovaries. Because Edn1, Apoa1, and Cited1 are known
to regulate angiogenesis, PGR may affect the neovascularization of
follicles that is initiated with ovulation.},
url = {http://www.biolreprod.org/cgi/content/abstract/82/2/402}
}
@ARTICLE{Sritanaudomchai2010,
author = {Sritanaudomchai, Hathaitip and Ma, Hong and Clepper, Lisa and Gokhale,
Sumita and Bogan, Randy and Hennebold, Jon and Wolf, Don and Mitalipov,
Shoukhrat},
title = {Discovery of a novel imprinted gene by transcriptional analysis of
parthenogenetic embryonic stem cells},
journal = {Hum. Reprod.},
year = {2010},
volume = {25},
pages = {1927--1941},
number = {8},
month = aug,
abstract = {BACKGROUNDParthenogenetic embryonic stem cells (PESCs) may have future
utilities in cell replacement therapies since they are closely related
to the female from which the activated oocyte was obtained. Furthermore,
the avoidance of parthenogenetic development in mammals provides
the most compelling rationale for the evolution of genomic imprinting,
and the biological process of parthenogenesis raises complex issues
regarding differential gene expression. METHODS AND RESULTSWe describe
here homozygous rhesus monkey PESCs derived from a spontaneously
duplicated, haploid oocyte genome. Since the effect of homozygosity
on PESCs pluripotency and differentiation potential is unknown, we
assessed the similarities and differences in pluripotency markers
and developmental potential by in vitro and in vivo differentiation
of homozygous and heterozygous PESCs. To understand the differences
in gene expression regulation between parthenogenetic and biparental
embryonic stem cells (ESCs), we conducted microarray analysis of
genome-wide mRNA profiles of primate PESCs and ESCs derived from
fertilized embryos using the Affymetrix Rhesus Macaque Genome array.
Several known paternally imprinted genes were in the highly down-regulated
group in PESCs compared with ESCs. Furthermore, allele-specific expression
analysis of other genes whose expression is also down-regulated in
PESCs, led to the identification of one novel imprinted gene, inositol
polyphosphate-5-phosphatase F (INPP5F), which was exclusively expressed
from a paternal allele. CONCLUSIONOur findings suggest that PESCs
could be used as a model for studying genomic imprinting, and in
the discovery of novel imprinted genes.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/25/8/1927}
}
@ARTICLE{Srivastava2011,
author = {Srivastava, Anuj and Rogers, Willie L. and Breton, Catherine M. and
Cai, Liming and Malmberg, Russell L.},
title = {Transcriptome Analysis of Sarracenia, an Insectivorous Plant},
journal = {DNA Res},
year = {2011},
volume = {18},
pages = {253-261},
number = {4},
abstract = {Sarracenia species (pitcher plants) are carnivorous plants which obtain
a portion of their nutrients from insects captured in the pitchers.
To investigate these plants, we sequenced the transcriptome of two
species, Sarracenia psittacina and Sarracenia purpurea, using Roche
454 pyrosequencing technology. We obtained 46 275 and 36 681 contigs
by de novo assembly methods for S. psittacina and S. purpurea, respectively,
and further identified 16 163 orthologous contigs between them. Estimation
of synonymous substitution rates between orthologous and paralogous
contigs indicates the events of genome duplication and speciation
within the Sarracenia genus both occurred [~]2 million years ago.
The ratios of synonymous and non-synonymous substitution rates indicated
that 491 contigs have been under positive selection (Ka/Ks > 1).
Significant proportions of these contigs were involved in functions
related to binding activity. We also found that the greatest sequence
similarity for both of these species was to Vitis vinifera, which
is most consistent with a non-current classification of the order
Ericales as an asterid. This study has provided new insights into
pitcher plants and will contribute greatly to future research on
this genus and its distinctive ecological adaptations.},
doi = {10.1093/dnares/dsr014},
eprint = {http://dnaresearch.oxfordjournals.org/cgi/reprint/18/4/253.pdf},
url = {http://dnaresearch.oxfordjournals.org/cgi/content/abstract/18/4/253}
}
@ARTICLE{Srivastava2008,
author = {Srivastava, Alaka and Wang, Jianghua and Zhou, Hui and Melvin, James
E. and Wong, David T.},
title = {Age and gender related differences in human parotid gland gene expression},
journal = {Archives of Oral Biology},
year = {2008},
volume = {53},
pages = {1058--1070},
number = {11},
month = nov,
abstract = {Objective The present study evaluated differences in gene expression
associated with age and gender in the human parotid gland.Design
Parotid gland tissue was analysed using the Affymetrix® GeneChip®
HGU133plus2.0 array.Results Differential gene expression, defined
as a statistically significant difference with a 1.5-fold or greater
change, was detected in 787 gene probe sets; 467 (~59%) showed higher
expression in females. Several genes associated with saliva secretion
were differentially expressed in male and female parotid glands including
vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated
protein SNAP23, RAS oncogene family member RAB1A and the syntaxin
binding protein STXBP1. Evaluation of gene expression in the youngest
and the oldest female subjects revealed that the expression of 228
probe sets were altered during aging; 155 genes were up-regulated
in the aged female parotid gland. However, of the genes that were
altered during aging, 22 of the 30 probes (73%) classified as being
associated with immune responses were down-regulated in the aged
parotid gland. A panel of differentially expressed, age- and gender-related
genes was selected for validation by quantitative, real-time RT-PCR.
Comparable differences in gene expression were detected by both Affymetrix®
array and quantitative, real-time RT-PCR methods.Conclusions Our
data suggest that salivary gland function may be adversely affected
in the aged population due, at least in part, to the altered regulation
of several categories of genes. Moreover, the gender specific differences
in gene expression identified in the present study correlate with
the previously observed sexual dimorphism in salivary gland function.},
issn = {0003-9969},
keywords = {Human parotid, Salivary gland, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6T4J-4ST4CG7-1/2/5213e225ea37c9e685f7eb41283399f7}
}
@ARTICLE{Srivastava2007,
author = {Srivastava, Apurva K. and Qin, Xuezhong and Wedhas, Nia and Arnush,
Marc and Linkhart, Thomas A. and Chadwick, Robert B. and Kumar, Ashok},
title = {Tumor Necrosis Factor-{alpha} Augments Matrix Metalloproteinase-9
Production in Skeletal Muscle Cells through the Activation of Transforming
Growth Factor- -activated Kinase 1 (TAK1)-dependent Signaling Pathway},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {35113--35124},
number = {48},
month = nov,
abstract = {We have investigated the effect of tumor necrosis factor-{alpha} (TNF-{alpha})
on the production of extracellular matrix-degrading proteases in
skeletal muscles. Using microarray, quantitative PCR, Western blotting,
and zymography, we found that TNF-{alpha} drastically increases the
production of matrix metalloproteinase (MMP)-9 from C2C12 myotubes.
In vivo administration of TNF-{alpha} in mice increased the transcript
level of MMP-9 in skeletal muscle tissues. Although TNF-{alpha} activated
all the three MAPKs (i.e. ERK1/2, JNK, and p38), inhibition of ERK1/2
or p38 but not JNK blunted the TNF-{alpha}-induced production of
MMP-9 from myotubes. Inhibition of Akt also inhibited the TNF-{alpha}-induced
production of MMP-9. TNF-{alpha} increased the activation of transcription
factors NF-{kappa}B and AP-1 but not SP-1 in myotubes. Overexpression
of a dominant negative inhibitor of NF-{kappa}B or AP-1 blocked the
TNF-{alpha}-induced expression of MMP-9 in myotubes. Similarly, point
mutations in AP-1- or NF-{kappa}B-binding sites in MMP-9 promoter
inhibited the TNF-{alpha}-induced expression of a reporter gene.
TNF-{alpha} increased the activity of transforming growth factor-{beta}-activating
kinase-1 (TAK1). Furthermore, overexpression of a dominant negative
mutant of TAK1 blocked the TNF-{alpha}-induced expression of MMP-9
and activation of NF-{kappa}B and AP-1. Our results also suggest
that TNF-{alpha} induces MMP-9 expression in muscle cells through
the recruitment of TRAF-2, Fas-associated protein with death domain,
and TNF receptor-associated protein with death domain but not NIK
or TRAF-6 proteins. We conclude that TAK1-mediated pathways are involved
in TNF-{alpha}-induced MMP-9 production in skeletal muscle cells.},
url = {http://www.jbc.org/cgi/content/abstract/282/48/35113}
}
@ARTICLE{Srivastava2010a,
author = {Srivastava, A. K. and Ramaswamy, N. K. and Suprasanna, P. and D'Souza,
S. F.},
title = {Genome-wide analysis of thiourea-modulated salinity stress-responsive
transcripts in seeds of Brassica juncea: identification of signalling
and effector components of stress tolerance},
journal = {Ann. Bot.},
year = {2010},
volume = {106},
pages = {663--674},
number = {5},
month = nov,
abstract = {Background and AimsAbiotic stresses including salinity are the major
constraints to crop production. In this regard, the use of thiourea
(TU) in imparting salinity-stress tolerance to Indian mustard (Brassica
juncea) has been demonstrated earlier. To gain an insight into the
mechanism of TU action, various molecular and biochemical studies
were conducted. MethodsMicroarray analysis was performed in seeds
subjected to distilled water (control), 1 M NaCl, 1 M NaCl + 6{middle
dot}5 mM TU and 6{middle dot}5 mM TU alone for 1 h. Real-time PCR
validation of selected genes and biochemical studies were conducted
under similar treatments at 1 h and 6 h. Key ResultsThe microarray
analysis revealed a differential expression profile of 33 genes in
NaCl- and NaCl + TU-treated seeds, most of which are established
markers of stress tolerance. The temporal regulation of eight selected
genes by real-time PCR indicated their early and co-ordinated induction
at 1 h in NaCl + TU only. Besides, NaCl + TU-treated seeds also maintained
a higher level of abscisic acid, reduced to oxidized glutathione
(GSH : GSSG) ratio and activities of catalase, phenylalanine ammonia
lyase and glutathione-S-transferases, as compared with that of NaCl
treatment. The addition of LaCl3 (a specific calcium-channel blocker)
restricted the responses of TU both at molecular and biochemical
level suggesting the possible involvement of a cytosolic calcium
burst in the TU-mediated response. The TU-alone treatment was comparable
to that of the control; however, it reduced the expression of some
transcription factors and heat-shock proteins presumably due to the
stabilization of the corresponding proteins. ConclusionsThe TU treatment
co-ordinately regulates different signalling and effector mechanisms
at an early stage to alleviate stress even under a high degree of
salinity. This also indicates the potential of TU to be used as an
effective bioregulator to impart salinity tolerance under field conditions.},
url = {http://aob.oxfordjournals.org/cgi/content/abstract/106/5/663}
}
@ARTICLE{Srivastava2005,
author = {Srivastava, Mrigank and Jung, Steffen and Wilhelm, Jochen and Fink,
Ludger and Buhling, Frank and Welte, Tobias and Bohle, Rainer M.
and Seeger, Werner and Lohmeyer, Jurgen and Maus, Ulrich A.},
title = {The Inflammatory versus Constitutive Trafficking of Mononuclear Phagocytes
into the Alveolar Space of Mice Is Associated with Drastic Changes
in Their Gene Expression Profiles},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {1884--1893},
number = {3},
month = aug,
abstract = {Mononuclear phagocytes enter the lungs both constitutively to maintain
alveolar macrophage and dendritic cell homeostasis, as well as during
lung inflammation, where the role of these cells is less well defined.
We used a transgenic mouse strain (CX3CR1+/GFP) that harbors a GFP
label in circulating monocytes to identify and sort these cells from
the vascular and alveolar compartments under both constitutive and
acute lung inflammatory conditions. Using nylon arrays combined with
real-time RT-PCR for gene expression profiling, we found that flow-sorted,
highly purified mononuclear phagocytes recruited to acutely inflamed
mouse lungs showed strongly up-regulated mRNA levels of the neutrophil
chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar
mononuclear phagocytes that immigrated in steady state. Similar observations
were made for the lysosomal cathepsins B, L, and K being strongly
up-regulated in mononuclear phagocytes upon recruitment to inflamed
lungs but not during constitutive alveolar immigration. Inflammatory
elicited mononuclear phagocytes also demonstrated significantly increased
mRNA levels of the cytokine TNF-{alpha} and the PRR-associated molecules
CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear
phagocytes exhibit strongly increased neutrophil chemoattractants,
lysosomal proteases, and LPS signaling mRNA transcripts, suggesting
that these cells may play a major role in acute lung inflammatory
processes.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/3/1884}
}
@ARTICLE{Srivastava2007a,
author = {Srivastava, Mrigank and Meinders, Antje and Steinwede, Kathrin and
Maus, Regina and Lucke, Nadine and Bühling, Frank and Ehlers, Stefan
and Welte, Tobias and Maus, Ulrich A.},
title = {Mediator responses of alveolar macrophages and kinetics of mononuclear
phagocyte subset recruitment during acute primary and secondary mycobacterial
infections in the lungs of mice},
journal = {Cellular Microbiology},
year = {2007},
volume = {9},
pages = {738--752},
number = {3},
abstract = {Summary Little is known about the activation programme induced in
alveolar macrophages upon phagocytosis of mycobacteria and the concomitant
mononuclear phagocyte migratory responses that shape the acute phase
of mycobacterial infection. Using high-speed cell sorting in conjunction
with real-time RT-PCR analysis, we show that sorted alveolar macrophages
of transgenic CX3CR1+/GFP mice infected with red fluorescent-labelled
Mycobacterium bovis BCG exhibited weak transcriptional changes of
lysosomal cathepsins B, L, D, K and S, whereas antimicrobial cathepsin
G was strongly induced upon infection. Moreover, mRNA levels of pattern
recognition receptors TLR2, TLR4 and NOD2 were downregulated as were
neutrophil chemoattractants KC, MIP-2 and IP-10, whereas highly upregulated
mRNA levels of the monocyte chemoattractant CCL2 were observed. M. bovis
BCG infection of the mice elicited the alveolar accumulation of highly
CX3CR1-positive alveolar dendritic cells but not neutrophils within
the alveolar compartment, whereas no increased accumulation of CX3CR1high
lung parenchymal dendritic cells (lung DC) or CX3CR1neg lung macrophages
compared with controls was noted. In contrast, CX3CR1+/GFP mice previously
immunized with M. bovis BCG rapidly responded with increased accumulations
of both CX3CR1high alveolar and lung parenchymal DC and CX3CR1neg
lung macrophages upon intratracheal M. bovis BCG challenge. Moreover,
alveolar and lung macrophages and lung DC were found to contribute
to early uptake of M. bovis BCG. Together, acute mycobacterial infection
triggers both rapid changes in gene expression profiles in infected
alveolar macrophages and a compartment-specific accumulation of mononuclear
phagocyte subsets contributing to M. bovis BCG uptake in vivo.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2006.00824.x}
}
@ARTICLE{Srivastava2008a,
author = {Srivastava, Mrigank and Steinwede, Kathrin and Kiviranta, Riku and
Morko, Jukka and Hoymann, Heinz-Gerd and Länger, Florian and Buhling,
Frank and Welte, Tobias and Maus, Ulrich},
title = {Overexpression of cathepsin K in mice decreases collagen deposition
and lung resistance in response to bleomycin-induced pulmonary fibrosis},
journal = {Respiratory Research},
year = {2008},
volume = {9},
pages = {54},
number = {1},
abstract = {BACKGROUND:Lung fibrosis is a devastating pulmonary disorder characterized
by alveolar epithelial injury, extracellular matrix deposition and
scar tissue formation. Due to its potent collagenolytic activity,
cathepsin K, a lysosomal cysteine protease is an interesting target
molecule with therapeutic potential to attenuate bleomycin-induced
pulmonary fibrosis in mice. We here tested the hypothesis that over-expression
of cathepsin K in the lungs of mice is protective in bleomycin-induced
pulmonary fibrosis.METHODS:Wild-type and cathepsin K overexpressing
(cathepsin K transgenic; cath K tg) mice were challenged intratracheally
with bleomycin and sacrificed at 1, 2, 3 and 4 weeks post-treatment
followed by determination of lung fibrosis by estimating lung collagen
content, lung histopathology, leukocytic infiltrates and lung function.
In addition, changes in cathepsin K protein levels in the lung were
determined by immunohistochemistry, real time RT-PCR and western
blotting.RESULTS:Cathepsin K protein levels were strongly increased
in alveolar macrophages and lung parenchymal tissue of mock-treated
cathepsin K transgenic (cath K tg) mice relative to wild-type mice
and further increased particularly in cath K tg but also wild-type
mice in response to bleomycin. Moreover, cath K tg mice responded
with a lower collagen deposition in their lungs, which was accompanied
by a significantly lower lung resistance (RL) compared to bleomycin-treated
wild-type mice. In addition, cath K tg mice responded with a lower
degree of lung fibrosis than wild-type mice, a process that was found
to be independent of inflammatory leukocyte mobilization in response
to bleomycin challenge.CONCLUSION:Over-expression of cathepsin K
reduced lung collagen deposition and improved lung function parameters
in the lungs of transgenic mice, thereby providing at least partial
protection against bleomycin-induced lung fibrosis.},
doi = {10.1186/1465-9921-9-54},
issn = {1465-9921},
pubmedid = {18638383},
url = {http://respiratory-research.com/content/9/1/54}
}
@ARTICLE{Srivastava2008b,
author = {Srivastava, Prashant K. and Küffer, Stefan and Brors, Benedikt and
Shahi, Priyanka and Li, Li and Kenzelmann, Marc and Gretz, Norbert
and Gröne, Hermann-Josef},
title = {A cut-off based approach for gene expression analysis of formalin-fixed
and paraffin-embedded tissue samples},
journal = {Genomics},
year = {2008},
volume = {91},
pages = {522--529},
number = {6},
month = jun,
abstract = {Microarray analysis of formalin-fixed and paraffin-embedded (FFPE)
tissue seems to be of importance for the detection of molecular marker
sets in prostate cancer (PC). The compromised RNA integrity of FFPE
tissue results in a high degree of variability at the probe level
of microarray data as shown by degradation plot. We tested methods
that reduce the variability by including all probes within 300 nucleotides,
within 600 nucleotides, or up to a calculated breakpoint with reference
to the 3'-end. Accepted PC pathways such as the Wnt signaling pathway
could be observed to be significantly regulated within FFPE microarray
datasets. The best representation of PC gene expression, as well
as better comparability to meta-analysis and fresh-frozen microarray
data, could be obtained with a 600-nucleotide cutoff. Beyond the
specific impact for PC microarray data analysis we propose a cutoff
of 600 nucleotides for samples for which the integrity of the RNA
cannot be guaranteed.},
issn = {0888-7543},
keywords = {Formalin-fixed paraffin embedded tissue, Microarray, Degradation plot,
Constant cut-off, Breakpoint},
url = {http://www.sciencedirect.com/science/article/B6WG1-4SJ9G7C-1/2/529864af68847a11ba89da33df6e34c5}
}
@ARTICLE{Srivastava2010,
author = {Srivastava, Shivani and Macaubas, Claudia and Deshpande, Chetan and
Alexander, Heather C. and Chang, Sheng-Yung and Sun, Yue and Park,
Jane L. and Lee, Tzielan and Begovich, Ann and Mellins, Elizabeth
D.},
title = {Monocytes are resistant to apoptosis in systemic juvenile idiopathic
arthritis},
journal = {Clinical Immunology},
year = {2010},
volume = {136},
pages = {257--268},
number = {2},
month = aug,
abstract = {We investigated whether circulating monocytes from patients with systemic
juvenile idiopathic arthritis (SJIA) are resistant to apoptosis and
which apoptotic pathway(s) may mediate this resistance. A microarray
analysis of peripheral blood mononuclear cells (PBMC) of SJIA samples
and RT-PCR analysis of isolated monocytes showed that monocytes from
active SJIA patients express transcripts that imply resistance to
apoptosis. SJIA monocytes incubated in low serum show reduced annexin
binding and diminished FasL up-regulation compared to controls. SJIA
monocytes are less susceptible to anti-Fas-induced apoptosis and,
upon activation of the mitochondrial pathway with staurosporine,
show diminished Bid cleavage and Bcl-w down-regulation compared to
controls. Exposure to SJIA plasma reduces responses to apoptotic
triggers in normal monocytes. Thus, SJIA monocytes are resistant
to apoptosis due to alterations in both the extrinsic and intrinsic
apoptosis pathways, and circulating factors associated with active
SJIA may confer this phenotype.},
issn = {1521-6616},
keywords = {Systemic juvenile arthritis, Monocytes, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6WCJ-5027F29-1/2/ab4ddcad4d1ad66d244a7d2c154be25c}
}
@ARTICLE{Sriwijitkamol2007,
author = {Sriwijitkamol, Apiradee and Coletta, Dawn K. and Wajcberg, Estela
and Balbontin, Gabriela B. and Reyna, Sara M. and Barrientes, John
and Eagan, Phyllis A. and Jenkinson, Christopher P. and Cersosimo,
Eugenio and DeFronzo, Ralph A. and Sakamoto, Kei and Musi, Nicolas},
title = {Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of
Subjects With Type 2 Diabetes: A Time-Course and Dose-Response Study},
journal = {Diabetes},
year = {2007},
volume = {56},
pages = {836--848},
number = {3},
month = mar,
abstract = {Activation of AMP-activated protein kinase (AMPK) by exercise induces
several cellular processes in muscle. Exercise activation of AMPK
is unaffected in lean (BMI [~]25 kg/m2) subjects with type 2 diabetes.
However, most type 2 diabetic subjects are obese (BMI >30 kg/m2),
and exercise stimulation of AMPK is blunted in obese rodents. We
examined whether obese type 2 diabetic subjects have impaired exercise
stimulation of AMPK, at different signaling levels, spanning from
the upstream kinase, LKB1, to the putative AMPK targets, AS160 and
peroxisome proliferator-activated receptor coactivator (PGC)-1{alpha},
involved in glucose transport regulation and mitochondrial biogenesis,
respectively. Twelve type 2 diabetic, eight obese, and eight lean
subjects exercised on a cycle ergometer for 40 min. Muscle biopsies
were done before, during, and after exercise. Subjects underwent
this protocol on two occasions, at low (50% VO2max) and moderate
(70% VO2max) intensities, with a 4-6 week interval. Exercise had
no effect on LKB1 activity. Exercise had a time- and intensity-dependent
effect to increase AMPK activity and AS160 phosphorylation. Obese
and type 2 diabetic subjects had attenuated exercise-stimulated AMPK
activity and AS160 phosphorylation. Type 2 diabetic subjects had
reduced basal PGC-1 gene expression but normal exercise-induced increases
in PGC-1 expression. Our findings suggest that obese type 2 diabetic
subjects may need to exercise at higher intensity to stimulate the
AMPK-AS160 axis to the same level as lean subjects.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/56/3/836}
}
@ARTICLE{StMartin2007,
author = {St Martin, Jessie L. and Klucken, Jochen and Outeiro, Tiago F. and
Nguyen, Paul and Keller-McGandy, Christine and Cantuti-Castelvetri,
Ippolita and Grammatopoulos, Tom N. and Standaert, David G. and Hyman,
Bradley T. and McLean, Pamela J.},
title = {Dopaminergic neuron loss and up-regulation of chaperone protein mRNA
induced by targeted over-expression of alpha-synuclein in mouse substantia
nigra},
journal = {Journal of Neurochemistry},
year = {2007},
volume = {100},
pages = {1449--1457},
number = {6},
abstract = {Abstract Several transgenic mouse lines with altered α-synuclein
expression have been developed that show a variety of Parkinson’s
disease-like symptoms without specific loss of dopaminergic neurons.
Targeted over-expression of human α-synuclein using viral-vector
mediated gene delivery into the substantia nigra of rats and non-human
primates leads to dopaminergic cell loss and the formation of α-synuclein
aggregates reminiscent of Lewy bodies. In the context of these recent
findings, we used adeno-associated virus (AAV) to over-express wild
type human α-synuclein in the substantia nigra of mice. We hypothesized
that this over-expression would recapitulate pathological hallmarks
of Parkinson’s disease, creating a mouse model to further characterize
the disease pathogenesis. Recombinant AAV expressing α-synuclein
was stereotaxically injected into the substantia nigra of mice, leading
to a 25% reduction of dopaminergic neurons after 24Â weeks of transduction.
Furthermore, examination of mRNA levels of stress-related proteins
using laser capture microdissection and quantitative PCR revealed
a positive correlation of Hsp27 expression with the extent of viral
transduction at 4Â weeks and a positive correlation of Hsp40, Hsp70
and caspase 9 with the extent of viral transduction at 24Â weeks.
Taken together, our findings suggest that targeted over-expression
of α-synuclein can induce pathology at the gross anatomical and
molecular level in the substantia nigra, providing a mouse model
in which upstream changes in Parkinson’s disease pathogenesis can
be further elucidated.},
issn = {1471-4159},
keywords = {adeno-associated virus, heat shock proteins, laser capture microdissection,
Parkinson’s disease, substantia nigra, α-synuclein},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2006.04310.x}
}
@ARTICLE{ST-CYR2008,
author = {ST-CYR, J. and DEROME, N. and BERNATCHEZ, L.},
title = {The transcriptomics of life-history trade-offs in whitefish species
pairs (Coregonus sp.)},
journal = {Molecular Ecology},
year = {2008},
volume = {17},
pages = {1850--1870},
number = {7},
abstract = {Abstract Despite the progress achieved in elucidating the ecological
mechanisms of adaptive radiation, there has been little focus on
documenting the extent of adaptive differentiation in physiological
functions during this process. Moreover, a thorough understanding
of the genomic basis underlying phenotypic adaptive divergence is
still in its infancy. One important evolutionary process for which
causal genetic mechanisms are largely unknown pertains to life-history
trade-offs. We analysed patterns of gene transcription in liver tissue
of sympatric dwarf and normal whitefish from two natural lakes, as
well as from populations reared in controlled environments, using
a 16Â 006-gene cDNA microarray in order to: (i) document the extent
of physiological adaptive divergence between sympatric dwarf and
normal species pairs, and (ii) explore the molecular mechanisms of
differential life history trade-offs between growth and survival
potentially involved in their adaptive divergence. In the two natural
lakes, 6.45% of significantly transcribed genes showed regulation
either in parallel fashion (2.39%) or in different directions (4.06%).
Among genes showing parallelism in regulation patterns, we observed
a higher proportion of over-expressed genes in dwarf relative to
normal whitefish (70.6%). Patterns observed in controlled conditions
were also generally congruent with those observed in natural populations.
Dwarf whitefish consistently showed significant over-expression of
genes potentially associated with survival through enhanced activity
(energy metabolism, iron homeostasis, lipid metabolism, detoxification),
whereas more genes associated with growth (protein synthesis, cell
cycle, cell growth) were generally down-regulated in dwarf relative
to normal whitefish. Overall, parallelism in patterns of gene transcription,
as well as patterns of interindividual variation across controlled
and natural environments, provide strong indirect evidence for the
role of selection in the evolution of differential regulation of
genes involving a vast array of potentially adaptive physiological
processes between dwarf and normal whitefish. Our results also provide
a first mechanistic, genomic basis for the observed trade-off in
life-history traits distinguishing dwarf and normal whitefish species
pairs, wherein enhanced survival via more active swimming, necessary
for increased foraging and predator avoidance, engages energetic
costs that translate into slower growth rate and reduced fecundity
in dwarf relative to normal whitefish.},
issn = {1365-294X},
keywords = {adaptive radiation, fish, functional genomics, life history trade-offs,
microarray, parallel evolution, speciation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2008.03696.x}
}
@ARTICLE{Staab2007,
author = {Staab, Claudia A. and Ceder, Rebecca and Jägerbrink, Theres and
Nilsson, Jan-Anders and Roberg, Karin and Jörnvall, Hans and Höög,
Jan-Olov and Grafström, Roland C.},
title = {Bioinformatics Processing of Protein and Transcript Profiles of Normal
and Transformed Cell Lines Indicates Functional Impairment of Transcriptional
Regulators in Buccal Carcinoma},
journal = {Journal of Proteome Research},
year = {2007},
volume = {6},
pages = {3705-3717},
number = {9},
doi = {10.1021/pr070308q},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr070308q},
url = {http://pubs.acs.org/doi/abs/10.1021/pr070308q}
}
@ARTICLE{Staal2007,
author = {Staal, Yvonne C.M. and Hebels, Dennie G.A.J. and van Herwijnen, Marcel
H.M. and Gottschalk, Ralph W.H. and van Schooten, Frederik J. and
van Delft, Joost H.M.},
title = {Binary PAH mixtures cause additive or antagonistic effects on gene
expression but synergistic effects on DNA adduct formation},
journal = {Carcinogenesis},
year = {2007},
volume = {28},
pages = {2632--2640},
number = {12},
month = dec,
abstract = {Polycyclic aromatic hydrocarbons (PAHs) cover a wide range of structurally
related compounds which differ greatly in their carcinogenic potency.
PAH exposure usually occurs through mixtures rather than individual
compounds. Therefore, we assessed whether the effects of binary PAH
mixtures on gene expression, DNA adduct formation, apoptosis and
cell cycle are additive compared with the effects of the individual
compounds in human hepatoma cells (HepG2). Equimolar and equitoxic
mixtures of benzo[a]pyrene (B[a]P) with either dibenzo[a,l]pyrene
(DB[a,l]P), dibenzo[a,h]anthracene (DB[a,h]A), benzo[b]fluoranthene
(B[b]F), fluoranthene (FA) or 1-methylphenanthrene (1-MPA) were studied.
DB[a,l]P, B[a]P, DB[a,h]A and B[b]F dose-dependently increased apoptosis
and blocked cells cycle in S-phase. PAH mixtures showed an additive
effect on apoptosis and on cell cycle blockage. DNA adduct formation
in mixtures was higher than expected based on the individual compounds,
indicating a synergistic effect of PAH mixtures. Equimolar mixtures
of B[a]P and DB[a,l]P (0.1, 0.3 and 1.0 {micro}M) were assessed for
their effects on gene expression. Only at 1.0 {micro}M, the mixture
showed antagonism. All five compounds were also tested as a binary
mixture with B[a]P in equitoxic concentrations. The combinations
of B[a]P with B[b]F, DB[a,h]A or FA showed additivity, whereas B[a]P
with DB[a,l]P or 1-MPA showed antagonism. Many individual genes showed
additivity in mixtures, but some genes showed mostly antagonism or
synergism. Our results show that the effects of binary mixtures of
PAHs on gene expression are generally additive or slightly antagonistic,
suggesting no effect or decreased carcinogenic potency, whereas the
effects on DNA adduct formation show synergism, which rather indicates
increased carcinogenic potency.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/28/12/2632}
}
@ARTICLE{Staal2007a,
author = {Staal, Yvonne C.M. and van Herwijnen, Marcel H.M. and Pushparajah,
Daphnee S. and Umachandran, Meera and Ioannides, Costas and van Schooten,
Frederik J. and van Delft, Joost H.M.},
title = {Modulation of gene expression and DNA-adduct formation in precision-cut
liver slices exposed to polycyclic aromatic hydrocarbons of different
carcinogenic potency},
journal = {Mutagenesis},
year = {2007},
volume = {22},
pages = {55--62},
number = {1},
month = jan,
abstract = {Polycyclic aromatic hydrocarbons (PAHs) differ markedly in their carcinogenic
potencies. Differences in transcriptomic responses upon PAH exposures
might improve our current understanding of the differences in carcinogenicity,
and therefore gene expression modulation by six PAHs in precision-cut
rat liver slices was investigated. Gene expression modulation by
benzo[a]pyrene (B[a]P), dibenzo[a,l]pyrene (DB[a,l]P), benzo[b]fluoranthene
(B[b]F), fluoranthene (FA), dibenzo[a,h]anthracene (DB[a,h]A) and
1-methylphenanthrene (1-MPA) was assessed after 6- (B[a]P, DB[a,l]P)
and 24-h (all compounds) exposure, using oligonucleotide arrays.
DNA-adduct formation was determined using 32P-post-labelling. The
effects of PAHs on gene expression and on DNA-adduct formation were
much more pronounced after 24-h exposure than after a 6-h exposure.
Each compound induced gene expression changes dose-dependently and
gene expression profiles were generally compound-specific. B[a]P,
B[b]F and DB[a,h]A displayed comparable gene expression profiles,
and so did DB[a,l]P, FA and 1-MPA. Only the carcinogenic PAHs (B[a]P,
B[b]F, DB[a,l]P and DB[a,h]A) induced the oxidative stress pathway.
DNA-adduct levels were: DB[a,l]P >> B[a]P > B[b]F [≥] DB[a,h]A
> FA [≥] 1-MPA. The expression of only a few genes was found to
correlate significantly with DNA-adduct formation, carcinogenic potency
or Ah-receptor binding capacity (the last two taken from literature).
These genes differed between the parameters. Our results indicate
that PAHs generally induce a compound-specific response on gene expression
and that discrimination of carcinogenic from non-carcinogenic compounds
is partly feasible using this approach. Only at a specific pathway
level, namely oxidative stress response, PAHs with high and low carcinogenic
potency could be discriminated.},
url = {http://mutage.oxfordjournals.org/cgi/content/abstract/22/1/55}
}
@ARTICLE{Staal2006,
author = {Staal, Yvonne C.M. and van Herwijnen, Marcel H.M. and van Schooten,
Frederik J. and van Delft, Joost H.M.},
title = {Modulation of gene expression and DNA adduct formation in HepG2 cells
by polycyclic aromatic hydrocarbons with different carcinogenic potencies},
journal = {Carcinogenesis},
year = {2006},
volume = {27},
pages = {646--655},
number = {3},
month = mar,
abstract = {Polycyclic aromatic hydrocarbons (PAHs) can occur in relatively high
concentrations in the air, and many PAHs are known or suspected carcinogens.
In order to better understand differences in carcinogenic potency
between PAHs, we investigated modulation of gene expression in human
HepG2 cells after 6 h incubation with varying doses of benzo[a]pyrene
(B[a]P), benzo[b]fluoranthene (B[b]F), fluoranthene (FA), dibenzo[a,h]anthracene
(DB[a,h]A), 1-methylphenanthrene (1-MPA) or dibenzo[a,l]pyrene (DB[a,l]P),
by using cDNA microarrays containing 600 toxicologically relevant
genes. Furthermore, DNA adduct levels induced by the compounds were
assessed with 32P-post-labeling, and carcinogenic potency was determined
by literature study. All tested PAHs, except 1-MPA, induced gene
expression changes in HepG2 cells, although generally no dose-response
relationship could be detected. Clustering and principal component
analysis showed that gene expression changes were compound specific,
since for each compound all concentrations grouped together. Furthermore,
it showed that the six PAHs can be divided into three groups, first
FA and 1-MPA, second B[a]P, B[b]F and DB[a,h]A, and third DB[a,l]P.
This grouping corresponds with the carcinogenic potencies of the
individual compounds. Many of the modulated genes are involved in
biological pathways like apoptosis, cholesterol biosynthesis and
fatty acid synthesis. The order of DNA adduct levels induced by the
PAHs was: B[a]P >> DB[a,l]P > B[b]F > DB[a,h]A > 1-MPA [≥] FA.
When comparing the expression change of individual genes with DNA
adduct levels, carcinogenic potency or Ah-receptor antagonicity (the
last two were taken from literature), several highly correlated genes
were found, of which CYP1A1, PRKCA, SLC22A3, NFKB1A, CYP1A2 and CYP2D6
correlated with all parameters. Our data indicate that discrimination
of high and low carcinogenic PAHs by gene expression profiling is
feasible. Also, the carcinogenic PAHs induce several pathways that
were not affected by the least carcinogenic PAHs.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/27/3/646}
}
@ARTICLE{Staal2008,
author = {Staal, Yvonne C. M. and Pushparajah, Daphnee S. and van Herwijnen,
Marcel H. M. and Gottschalk, Ralph W. H. and Maas, Lou M. and Ioannides,
Costas and van Schooten, Frederik J. and van Delft, Joost H. M.},
title = {Interactions between polycyclic aromatic hydrocarbons in binary mixtures:
Effects on gene expression and DNA adduct formation in precision-cut
rat liver slices},
journal = {Mutagenesis},
year = {2008},
volume = {23},
pages = {491--499},
number = {6},
month = nov,
abstract = {Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs
mostly through mixtures, hazard and risk assessment are mostly based
on the effects caused by individual compounds. The objective of the
current study was to investigate whether interactions between PAHs
occur, focusing on gene expression (as measured by cDNA microarrays)
and DNA adduct formation. The effects of benzo[a]pyrene or dibenzo[a,h]anthracene
(DB[a,h]A) alone and in binary mixtures with another PAH (DB[a,h]A,
benzo[b]fluoranthene, fluoranthene or dibenzo[a,l]pyrene) were investigated
using precision-cut rat liver slices. All compounds significantly
modulated the expression of several genes, but overlap between genes
affected by the mixture and by the individual compounds was relatively
small. All mixtures showed an antagonistic response on total gene
expression profiles. Moreover, at the level of individual genes,
mostly antagonism was evident, with additivity and synergism observed
for only a few genes. As far as DNA adduct formation is concerned,
the binary mixtures generally caused antagonism. The effects in liver
slices suggest a lower carcinogenic potency of PAH mixtures than
estimated based on additivity of individual compounds.},
url = {http://mutage.oxfordjournals.org/cgi/content/abstract/23/6/491}
}
@ARTICLE{Stables2011,
author = {Stables, Melanie J. and Shah, Sonia and Camon, Evelyn B. and Lovering,
Ruth C. and Newson, Justine and Bystrom, Jonas and Farrow, Stuart
and Gilroy, Derek W.},
title = {Transcriptomic analyses of murine resolution-phase macrophages},
journal = {Blood},
year = {2011},
volume = {118},
pages = {e192-208},
number = {26},
abstract = {Macrophages are either classically (M1) or alternatively-activated
(M2). Whereas this nomenclature was generated from monocyte-derived
macrophages treated in vitro with defined cytokine stimuli, the phenotype
of in vivo-derived macrophages is less understood. We completed Affymetrix-based
transcriptomic analysis of macrophages from the resolution phase
of a zymosan-induced peritonitis. Compared with macrophages from
hyperinflamed mice possessing a pro-inflammatory nature as well as
naive macrophages from the uninflamed peritoneum, resolution-phase
macrophages (rM) are similar to monocyte-derived dendritic cells
(DCs), being CD209a positive but lacking CD11c. They are enriched
for antigen processing/presentation (MHC class II [H2-Eb1, H2-Ab1,
H2-Ob, H2-Aa], CD74, CD86), secrete T- and B-lymphocyte chemokines
(Xcl1, Ccl5, Cxcl13) as well as factors that enhance macrophage/DC
development, and promote DC/T cell synapse formation (Clec2i, Tnfsf4,
Clcf1). rM are also enriched for cell cycle/proliferation genes as
well as Alox15, Timd4, and Tgfb2, key systems in the termination
of leukocyte trafficking and clearance of inflammatory cells. Finally,
comparison with in vitro-derived M1/M2 shows that rM are neither
classically nor alternatively activated but possess aspects of both
definitions consistent with an immune regulatory phenotype. We propose
that macrophages in situ cannot be rigidly categorized as they can
express many shades of the inflammatory spectrum determined by tissue,
stimulus, and phase of inflammation.},
doi = {10.1182/blood-2011-04-345330},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/26/e192.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/26/e192}
}
@ARTICLE{Stachowska2008,
author = {Stachowska, Ewa and Baskiewicz-Masiuk, Magdalena and Dziedziejko,
Violetta and Gutowska, Izabela and Baranowska-Bosiacka, Irena and
Marchlewicz, Mariola and Dolegowska, Barbara and Wiszniewska, Barbara
and Machalinski, Boguslaw and Chlubek, Dariusz},
title = {Conjugated linoleic acid increases intracellular ROS synthesis and
oxygenation of arachidonic acid in macrophages},
journal = {Nutrition},
year = {2008},
volume = {24},
pages = {187--199},
number = {2},
month = feb,
issn = {0899-9007},
keywords = {Macrophages, Conjugated linoleic acid, Reactive oxygen species, Isoprostanes},
url = {http://www.sciencedirect.com/science/article/B6TB0-4RFSVWY-B/2/f05a46c4225a72be5cf6a79aa95d31c5}
}
@ARTICLE{Staffas2011,
author = {Staffas, Anna and Kanduri, Meena and Hovland, Randi and Rosenquist,
Richard and Ommen, Hans Beier and Abrahamsson, Jonas and Forestier,
Erik and Jahnukainen, Kirsi and Jonsson, Olafur G. and Zeller, Bernward
and Palle, Josefine and Lonnerholm, Gudmar and Hasle, Henrik and
Palmqvist, Lars and Ehrencrona, Hans and on behalf of the Nordic
Society of Pediatric Hematology and Oncology (NOPHO), },
title = {Presence of FLT3-ITD and high BAALC expression are independent prognostic
markers in childhood acute myeloid leukemia},
journal = {Blood},
year = {2011},
volume = {118},
pages = {5905-5913},
number = {22},
abstract = {Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression
levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as
possible prognostic markers in acute myeloid leukemia (AML). We have
performed a thorough prognostic evaluation of these genetic markers
in patients with pediatric AML enrolled in the Nordic Society of
Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols.
Mutation status and expression levels were analyzed in 185 and 149
patients, respectively. Presence of FLT3-internal tandem duplication
(ITD) was associated with significantly inferior event-free survival
(EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD
correlated with significantly improved EFS. Furthermore, high levels
of ERG and BAALC transcripts were associated with inferior EFS. No
significant correlation with survival was seen for mutations in CEBPA
and WT1 or with gene expression levels of MN1, FLT3, and WT1. In
multivariate analysis, the presence of FLT3-ITD and high BAALC expression
were identified as independent prognostic markers of inferior EFS.
We conclude that analysis of the mutational status of FLT3 and NPM1
at diagnosis is important for prognostic stratification of patients
with pediatric AML and that determination of the BAALC gene expression
level can add valuable information.},
doi = {10.1182/blood-2011-05-353185},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/22/5905.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/22/5905}
}
@ARTICLE{Stagliano2001,
author = {Stagliano, Nancy E. And Carpino, Alan J. And Ross, Jeffrey S. And
Donovan, Michael},
title = {Vascular Gene Discovery Using Laser Capture Microdissection of Human
Blood Vessels and Quantitative PCR},
journal = {Annals of the New York Academy of Sciences},
year = {2001},
volume = {947},
pages = {344--349},
number = {1},
abstract = {Abstract: Recent approaches to candidate gene identification and cellular
localization have included RNA derived from complex whole tissue
profiling on cDNA microarrays followed by in situ hybridization with
riboprobes. In this study, the Arcturus PixCell IIâ„¢ laser capture
microdissection (LCM) system, an argon-based laser-assisted method
for the isolation of specific cell types from heterogeneous tissue
samples, was used to microdissect the tunica media from normal human
arteries and veins (n= 5 in each group). Total RNA was extracted
from the sum of 10,000 shots for each blood vessel using the Strataprep
MicroKit. RNA was reverse-transcribed, and the resulting cDNA was
analyzed using the Applied Biosystems 7700 quantitative PCR system
(Q-PCR). Control genes, such as the L-type calcium channel, PECAM
(CD-31), and beta-2 microglobulin, were used to assess sample quality
and purity. Of 10 laser-captured media samples, five (50%) showed
a gene profile that indicated high- quality RNA (abundance of housekeeping
genes) and smooth muscle cell enrichment (low levels of PECAM and
high levels of the L-type calcium channel). We conclude that the
application of the LCM technique to collect smooth muscle cell RNA
from the tunica media of human blood vessels can assist in the validation
of gene expression and potentially expedite the identification of
novel, regulated genes present within vascular smooth muscle.},
issn = {1749-6632},
keywords = {laser capture microdissection, Taqman, RT-PCR, blood vessels},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1749-6632.2001.tb03960.x}
}
@ARTICLE{Stahl2012,
author = {Stahl, Maximilian and Stahl, Klaus and Brubacher, Marie B. and Forrest,
John N., Jr.},
title = {Divergent CFTR orthologs respond differently to the channel inhibitors
CFTRinh-172, glibenclamide, and GlyH-101},
journal = {Am J Physiol Cell Physiol},
year = {2012},
volume = {302},
pages = {C67-76},
number = {1},
abstract = {Comparison of diverse orthologs is a powerful tool to study the structure
and function of channel proteins. We investigated the response of
human, killifish, pig, and shark cystic fibrosis transmembrane conductance
regulator (CFTR) to specific inhibitors of the channel: CFTRinh-172,
glibenclamide, and GlyH-101. In three systems, including organ perfusion
of the shark rectal gland, primary cultures of shark rectal gland
tubules, and expression studies of each ortholog in cRNA microinjected
Xenopus laevis oocytes, we observed fundamental differences in the
sensitivity to inhibition by these channel blockers. In organ perfusion
studies, shark CFTR was insensitive to inhibition by CFTRinh-172.
This insensitivity was also seen in short-circuit current experiments
with cultured rectal gland tubular epithelial cells (maximum inhibition
4 {+/-} 1.3%). In oocyte expression studies, shark CFTR was again
insensitive to CFTRinh-172 (maximum inhibition 10.3 {+/-} 2.5% at
25 M), pig CFTR was insensitive to glibenclamide (maximum inhibition
18.4 {+/-} 4.4% at 250 M), and all orthologs were sensitive to GlyH-101.
The amino acid residues considered responsible by previous site-directed
mutagenesis for binding of the three inhibitors are conserved in
the four CFTR isoforms studied. These experiments demonstrate a profound
difference in the sensitivity of different orthologs of CFTR proteins
to inhibition by CFTR blockers that cannot be explained by mutagenesis
of single amino acids. We believe that the potency of the inhibitors
CFTRinh-172, glibenclamide, and GlyH-101 on the CFTR chloride channel
protein is likely dictated by the local environment and the three-dimensional
structure of additional residues that form the vestibules, the chloride
pore, and regulatory regions of the channel.},
doi = {10.1152/ajpcell.00225.2011},
eprint = {http://ajpcell.physiology.org/cgi/reprint/302/1/C67.pdf},
url = {http://ajpcell.physiology.org/cgi/content/abstract/302/1/C67}
}
@ARTICLE{Stahl2005,
author = {Stahl, Sabine and Ittrich, Carina and Marx-Stoelting, Philip and
Köhle, Christoph and Altug-Teber, Özge and Riess, Olaf and Bonin,
Michael and Jobst, Jürgen and Kaiser, Stephan and Buchmann, Albrecht
and Schwarz, Michael},
title = {Genotype–phenotype relationships in hepatocellular tumors from
mice and man},
journal = {Hepatology},
year = {2005},
volume = {42},
pages = {353--361},
number = {2},
abstract = {Abstract 10.1002/hep.20768.abs Experimentally induced liver tumors
in mice harbor activating mutations in either Catnb (β-catenin)
or Ha-ras, according to the carcinogenic treatment. We have now investigated
by microarray analysis the gene expression profiles in tumors of
the two genotypes. In total, 364 genes or expressed sequences with
aberrant expression relative to normal liver were identified, but
only 30 of these demonstrated unidirectional changes in both tumor
types. Several functional clusters were identified that involve changes
in amino acid utilization and ammonia disposition in Catnb-mutated
tumors as opposed to alterations in lipid and cholesterol metabolism
in Ha-ras–mutated tumors. Moreover, several genes coding for inhibitory
molecules within the Wnt-signaling pathway were upregulated in Catnb-mutated
tumors, suggesting induction of a negative feedback loop, whereas
Ha-ras–mutated tumors showed alterations in the expression of several
genes functional in monomeric G-protein signaling. We conclude that
mouse hepatoma cells adopt different evolutionary strategies that
allow for their selective outgrowth under variable environmental
conditions. Human hepatocellular cancers (HCC) lack RAS mutations
but are frequently mutated in CTNNB1, the human Catnb ortholog. The
set of genes aberrantly expressed in Catnb-mutated mouse tumors was
used to screen, by expression profiling, for dysregulation of orthologous
genes within a panel of 25 HCCs, of which 10 were CTNNB1-mutated.
HCCs with activated β-catenin displayed a gene expression profile
that was similar to Catnb-mutated mouse tumors but distinct from
the other human HCCs. In conclusion, expression fingerprints may
be used for diagnostic purposes and potential new therapeutic intervention
strategies. Supplementary material for this article can be found
on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index/html).
(HEPATOLOGY 2005.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.20768}
}
@ARTICLE{Stahl2005a,
author = {Stahl, Sabine and Ittrich, Carina and Marx-Stoelting, Philip and
Köhle, Christoph and Ott, Thomas and Buchmann, Albrecht and Schwarz,
Michael},
title = {Effect of the tumor promoter phenobarbital on the pattern of global
gene expression in liver of connexin32-wild-type and connexin32-deficient
mice},
journal = {Int. J. Cancer},
year = {2005},
volume = {115},
pages = {861--869},
number = {6},
abstract = {Abstract 10.1002/ijc.20815.abs The antiepileptic drug phenobarbital
(PB) is used frequently as a model tumor promoter in rodent liver.
It is believed to increase the probability of cancer by accelerating
the clonal expansion of cells transformed during tumor initiation.
The molecular mechanism underlying this process is only partly understood
but seems to require the function of connexin32 (Cx32), one of the
2 gap junction proteins expressed in hepatocytes. PB mediates transcriptional
activation of various genes in liver but which of these are relevant
for tumor promotion is unknown. We have used oligonucleotide microarrays
to identify genes differentially modulated in expression by PB in
liver of Cx32-wild-type and Cx32-null mice. Mice of both strains
were kept on PB containing (0.05%) or control diet for 2 weeks. Total
liver RNA was isolated from 3 mice per experimental group and reverse
transcribed; cDNAs were hybridized to oligonucleotide microarrays
and a gene-by-gene linear model was used for statistical analysis
of data. Five genes were identified as induced or repressed in untreated
Cx32-null as compared to untreated Cx32-wild-type mice. PB affected
the expression of 53 genes, of which 13 code for members of Phase-I/II
of drug metabolism, and 12 genes were differentially affected in
expression by PB in Cx32-null as compared to Cx32-wild-type mice.
Among the differentially affected genes that could be verified by
quantitative RT-PCR or Western analysis were the insulin like growth
factor binding protein-1, retinol dehydrogenase-6 and the Y-chromosomally
located gene Dby, among which may be a candidate of relevance for
PB-mediated tumor promotion. © 2005 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {Connexin32, phenobarbital, hepatocarcinogenesis, gene expression profiling},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.20815}
}
@ARTICLE{Staib2010,
author = {Staib, Peter and Zaugg, Christophe and Mignon, Bernard and Weber,
Johann and Grumbt, Maria and Pradervand, Sylvain and Harshman, Keith
and Monod, Michel},
title = {Differential gene expression in the pathogenic dermatophyte Arthroderma
benhamiae in vitro versus during infection},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {884--895},
number = {3},
month = mar,
abstract = {Although dermatophytes are the most common agents of superficial mycoses
in humans and animals, the molecular basis of the pathogenicity of
these fungi is largely unknown. In vitro digestion of keratin by
dermatophytes is associated with the secretion of multiple proteases,
which are assumed to be responsible for their particular specialization
to colonize and degrade keratinized host structures during infection.
To investigate the role of individual secreted proteases in dermatophytosis,
a guinea pig infection model was established for the zoophilic dermatophyte
Arthroderma benhamiae, which causes highly inflammatory cutaneous
infections in humans and rodents. By use of a cDNA microarray covering
approximately 20-25 % of the A. benhamiae genome and containing sequences
of at least 23 protease genes, we revealed a distinct in vivo protease
gene expression profile in the fungal cells, which was surprisingly
different from the pattern elicited during in vitro growth on keratin.
Instead of the major in vitro-expressed proteases, others were activated
specifically during infection. These enzymes are therefore suggested
to fulfil important functions that are not exclusively associated
with the degradation of keratin. Most notably, the gene encoding
the serine protease subtilisin 6, which is a known major allergen
in the related dermatophyte Trichophyton rubrum and putatively linked
to host inflammation, was found to be the most strongly upregulated
gene during infection. In addition, our approach identified other
candidate pathogenicity-related factors in A. benhamiae, such as
genes encoding key enzymes of the glyoxylate cycle and an opsin-related
protein. Our work provides what we believe to be the first broad-scale
gene expression profile in human pathogenic dermatophytes during
infection, and points to putative virulence-associated mechanisms
that make these micro-organisms the most successful aetiological
agents of superficial mycoses.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/3/884}
}
@ARTICLE{Stam2010,
author = {Stam, Ronald W. and Schneider, Pauline and Hagelstein, Jill A. P.
and van der Linden, Marieke H. and Stumpel, Dominique J. P. M. and
de Menezes, Renee X. and de Lorenzo, Paola and Valsecchi, Maria G.
and Pieters, Rob},
title = {Gene expression profiling-based dissection of MLL translocated and
MLL germline acute lymphoblastic leukemia in infants},
journal = {Blood},
year = {2010},
volume = {115},
pages = {2835--2844},
number = {14},
month = apr,
abstract = {Acute lymphoblastic leukemia (ALL) in infants (< 1 year) is characterized
by a poor prognosis and a high incidence of MLL translocations. Several
studies demonstrated the unique gene expression profile associated
with MLL-rearranged ALL, but generally small cohorts were analyzed
as uniform patient groups regardless of the type of MLL translocation,
whereas the analysis of translocation-negative infant ALL remained
unacknowledged. Here we generated and analyzed primary infant ALL
expression profiles (n = 73) typified by translocations t(4;11),
t(11;19), and t(9;11), or the absence of MLL translocations. Our
data show that MLL germline infant ALL specifies a gene expression
pattern that is different from both MLL-rearranged infant ALL and
pediatric precursor B-ALL. Moreover, we demonstrate that, apart from
a fundamental signature shared by all MLL-rearranged infant ALL samples,
each type of MLL translocation is associated with a translocation-specific
gene expression signature. Finally, we show the existence of 2 distinct
subgroups among t(4;11)-positive infant ALL cases characterized by
the absence or presence of HOXA expression, and that patients lacking
HOXA expression are at extreme high risk of disease relapse. These
gene expression profiles should provide important novel insights
in the complex biology of MLL-rearranged infant ALL and boost our
progress in finding novel therapeutic solutions.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/14/2835}
}
@ARTICLE{Stamova2009,
author = {Stamova, Boryana and Apperson, Michelle and Walker, Wynn and Tian,
Yingfang and Xu, Huichun and Adamczy, Peter and Zhan, Xinhua and
Liu, Da-Zhi and Ander, Bradley and Liao, Isaac and Gregg, Jeffrey
and Turner, Renee and Jickling, Glen and Lit, Lisa and Sharp, Frank},
title = {Identification and validation of suitable endogenous reference genes
for gene expression studies in human peripheral blood},
journal = {BMC Medical Genomics},
year = {2009},
volume = {2},
pages = {49},
number = {1},
abstract = {BACKGROUND:Gene expression studies require appropriate normalization
methods. One such method uses stably expressed reference genes. Since
suitable reference genes appear to be unique for each tissue, we
have identified an optimal set of the most stably expressed genes
in human blood that can be used for normalization.METHODS:Whole-genome
Affymetrix Human 2.0 Plus arrays were examined from 526 samples of
males and females ages 2 to 78, including control subjects and patients
with Tourette syndrome, stroke, migraine, muscular dystrophy, and
autism. The top 100 most stably expressed genes with a broad range
of expression levels were identified. To validate the best candidate
genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1,
DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT),
4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and
PPIB, previously reported to be stably expressed in blood. Expression
stability and ranking analysis were performed using GeNorm and NormFinder
algorithms.RESULTS:Reference genes were ranked based on their expression
stability and the minimum number of genes needed for nomalization
as calculated using GeNorm showed that the fewest, most stably expressed
genes needed for acurate normalization in RNA expression studies
of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB.
We confirmed the ranking of the best candidate control genes by using
an alternative algorithm (NormFinder).CONCLUSION:The reference genes
identified in this study are stably expressed in whole blood of humans
of both genders with multiple disease conditions and ages 2 to 78.
Importantly, they also have different functions within cells and
thus should be expressed independently of each other. These genes
should be useful as normalization genes for microarray and RT-PCR
whole blood studies of human physiology, metabolism and disease.},
doi = {10.1186/1755-8794-2-49},
issn = {1755-8794},
pubmedid = {19656400},
url = {http://www.biomedcentral.com/1755-8794/2/49}
}
@ARTICLE{Stamper2010,
author = {Stamper, Brendan D. and Bammler, Theo K. and Beyer, Richard P. and
Farin, Frederico M. and Nelson, Sidney D.},
title = {Differential Regulation of Mitogen-Activated Protein Kinase Pathways
by Acetaminophen and Its Nonhepatotoxic Regioisomer 3'-Hydroxyacetanilide
in TAMH Cells},
journal = {Toxicol. Sci.},
year = {2010},
volume = {116},
pages = {164--173},
number = {1},
month = jul,
abstract = {Acetaminophen (APAP), a widely used analgesic and antipyretic that
is considered to be relatively safe at recommended doses, is the
leading cause of drug-induced liver failure in the United States.
3'-Hydroxyacetanilide (AMAP), a regioisomer of APAP, is useful as
a comparative tool for studying APAP-induced toxicity because it
is nontoxic relative to APAP. Transforming growth factor-alpha transgenic
mouse hepatocytes were treated with both isomers to investigate mitogen-activated
protein kinase (MAPK) cascades in order to differentiate their toxicological
outcomes. Posttranslational modifications of MAPK signaling were
assessed using immunoblotting and Bioplex technology, whereas gene
expression changes were measured using Affymetrix Mouse Gene 1.0
ST arrays. APAP treatment led to higher levels of glutathione depletion
at 6 and 24 h compared with AMAP in mitochondria. Glutathione depletion
was preceded by increased levels of c-Jun N-terminal kinase (JNK)
phosphorylation at 2 and 6 h after APAP treatment compared with AMAP,
whereas AMAP treatment led to increased extracellular signal-regulated
protein kinase (ERK) phosphorylation at 2 and 6 h compared with APAP.
Furthermore, APAP treatment significantly upregulated jun oncogene
(c-Jun) gene expression, which was confirmed by Western blotting
for both the phosphorylated and the nonphosphorylated forms of c-Jun
protein. Transfection with JNK siRNA attenuated APAP toxicity after
24 h, suggesting that higher levels of APAP-induced activation of
JNK were related to higher rates of cell death. In summary, genomic
regulation of MAPK-related transcription factors coupled with posttranslational
activation of their upstream kinases is critical in differentiating
the toxicities of APAP and AMAP.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/116/1/164}
}
@ARTICLE{Stan2006,
author = {Stan, Ana D. and Ghose, Subroto and Gao, Xue-Min and Roberts, Rosalinda
C. and Lewis-Amezcua, Kelly and Hatanpaa, Kimmo J. and Tamminga,
Carol A.},
title = {Human postmortem tissue: What quality markers matter?},
journal = {Brain Research},
year = {2006},
volume = {1123},
pages = {1--11},
number = {1},
month = dec,
abstract = {Postmortem human brain tissue is used for the study of many different
brain diseases. A key factor in conducting postmortem research is
the quality of the tissue. Unlike animal tissue, whose condition
at death can be controlled and influenced, human tissue can only
be collected naturalistically. This introduces potential confounds,
based both on pre- and postmortem conditions, that may influence
the quality of tissue and its ability to yield accurate results.
The traditionally recognized confounds that reduce tissue quality
are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time
of death), and long postmortem interval (PMI). We measured tissue
quality parameters in over 100 postmortem cases collected from different
sources and correlated them with RNA quality (as indicated by the
RNA Integrity Number (RIN)) and with protein quality (as measured
by the level of representative proteins). Our results show that the
most sensible indicator of tissue quality is RIN and that there is
a good correlation between RIN and the pH. No correlation developed
between protein levels and the aforementioned factors. Moreover,
even when RNA was degraded, the protein levels remained stable. However,
these correlations did not prove true under all circumstances (e.g.,
thawed tissue, surgical tissue), that yielded unexpected quality
indicators. These data also suggest that cases whose source was a
Medical Examiner's office represent high tissue quality.},
issn = {0006-8993},
keywords = {Brain, RIN, PMI, pH},
url = {http://www.sciencedirect.com/science/article/B6SYR-4M3J0YF-3/2/0332936f47871323492b66beeb12cb85}
}
@ARTICLE{Stanczyk2008,
author = {Stanczyk, Joanna and Pedrioli, Deena M. Leslie and Brentano, Fabia
and Sanchez-Pernaute, Olga and Kolling, Christoph and Gay, Renate
E. and Detmar, Michael and Gay, Steffen and Kyburz, Diego},
title = {Altered expression of MicroRNA in synovial fibroblasts and synovial
tissue in rheumatoid arthritis},
journal = {Arthritis \& Rheumatism},
year = {2008},
volume = {58},
pages = {1001--1009},
number = {4},
abstract = {Abstract 10.1002/art.23386.abs Objective MicroRNAs (miRNA) have recently
emerged as a new class of modulators of gene expression. In this
study we investigated the expression, regulation, and function of
miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts
(RASFs) and RA synovial tissue. Methods Locked nucleic acid microarray
was used to screen for differentially expressed miRNA in RASFs treated
with tumor necrosis factor α (TNFα). TaqMan-based real-time polymerase
chain reaction was applied to measure the levels of miR-155 and miR-146a.
Enforced overexpression of miR-155 was used to investigate the function
of miR-155 in RASFs. Results Microarray analysis of miRNA expressed
in RASFs treated with TNFα revealed a prominent up-regulation of
miR-155. Constitutive expression of both miR-155 and miR-146a was
higher in RASFs than in those from patients with osteoarthritis (OA),
and expression of miR-155 could be further induced by TNFα, interleukin-1β,
lipopolysaccharide, poly(I-C), and bacterial lipoprotein. The expression
of miR-155 in RA synovial tissue was higher than in OA synovial tissue.
Enforced expression of miR-155 in RASFs was found to repress the
levels of matrix metalloproteinase 3 (MMP-3) and reduce the induction
of MMPs 3 and 1 by Toll-like receptor ligands and cytokines. Moreover,
compared with monocytes from RA peripheral blood, RA synovial fluid
monocytes displayed higher levels of miR-155. Conclusion This study
provides the first description of increased expression of miRNA miR-155
and miR-146a in RA. Based on these findings, we postulate that the
inflammatory milieu may alter miRNA expression profiles in resident
cells of the rheumatoid joints. Considering the repressive effect
of miR-155 on the expression of MMPs 3 and 1 in RASFs, we hypothesize
that miR-155 may be involved in modulation of the destructive properties
of RASFs.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.23386}
}
@ARTICLE{Stanke-Labesque2009,
author = {Stanke-Labesque, Françoise and Bäck, Magnus and Lefebvre, Blandine
and Tamisier, Renaud and Baguet, Jean-Philippe and Arnol, Nathalie
and Lévy, Patrick and Pépin, Jean-Louis},
title = {Increased urinary leukotriene E4 excretion in obstructive sleep apnea:
Effects of obesity and hypoxia},
journal = {Journal of Allergy and Clinical Immunology},
year = {2009},
volume = {124},
pages = {364--370.e2},
number = {2},
month = aug,
abstract = {Background Low-grade inflammation may potentially explain the relationship
between obstructive sleep apnea syndrome (OSA) and cardiovascular
events. However, the respective contribution of intermittent hypoxia
and confounders, such as obesity, is still debated.Objectives To
monitor urinary leukotriene E4 (U-LTE4), a validated marker of proinflammatory
cysteinyl leukotriene production, in OSA; to determine the influence
of obesity and other confounders on U-LTE4 concentrations; to examine
the mechanisms involved through transcriptional profiling of the
leukotriene pathway in peripheral blood mononuclear cells (PBMCs);
and to investigate the effect of continuous positive air pressure
(CPAP) on U-LTE4 concentrations.Methods We measured U-LTE4 by liquid
chromatography-tandem mass spectrometry.Results The U-LTE4 concentrations
were increased (P = .019) in 40 nonobese patients with OSA carefully
matched for age, sex, and body mass index (BMI) to 25 control subjects,
and correlated (r = 0.0312; P = .017) to the percentage of time spent
with mean oxygen saturation (SaO2) less than 90%. In a larger cohort
of patients with OSA (n = 72), U-LTE4 increased as a function of
BMI (r = 0.445; P = .0002). In those patients, the expression levels
of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited
a similar pattern. A stepwise multiple linear regression analysis
performed in this cohort identified BMI (P = .001; regression coefficient,
3.33) and percentage of time spent with SaO2 <90% (P = .001; regression
coefficient, 1.01) as independent predictors of U-LTE4 concentrations.
Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE4 concentrations
only in patients with OSA with normal BMI.Conclusion Obesity, and
to a lesser extent hypoxia severity, are determinant of U-LTE4 production
in patients with OSA.},
issn = {0091-6749},
keywords = {Leukotriene E4, obstructive sleep apnea syndrome, nocturnal oxygen
desaturation, obesity},
url = {http://www.sciencedirect.com/science/article/B6WH4-4WRKF5X-2/2/1ed3180fd26ca8e668af9fa2a0fae951}
}
@ARTICLE{Stankiewicz2009,
author = {Stankiewicz, Monika J. and Crispino, John D.},
title = {ETS2 and ERG promote megakaryopoiesis and synergize with alterations
in GATA-1 to immortalize hematopoietic progenitor cells},
journal = {Blood},
year = {2009},
volume = {113},
pages = {3337--3347},
number = {14},
month = apr,
abstract = {ETS2 and ERG are transcription factors, encoded on human chromosome
21 (Hsa21), that have been implicated in human cancer. People with
Down syndrome (DS), who are trisomic for Hsa21, are predisposed to
acute megakaryoblastic leukemia (AMKL). DS-AMKL blasts harbor a mutation
in GATA1, which leads to loss of full-length protein but expression
of the GATA-1s isoform. To assess the consequences of ETS protein
misexpression on megakaryopoiesis, we expressed ETS2, ERG, and the
related protein FLI-1 in wild-type and Gata1 mutant murine fetal
liver progenitors. These studies revealed that ETS2, ERG, and FLI-1
facilitated the expansion of megakaryocytes from wild-type, Gata1-knockdown,
and Gata1s knockin progenitors, but none of the genes could overcome
the differentiation block characteristic of the Gata1-knockdown megakaryocytes.
Although overexpression of ETS proteins increased the proportion
of CD41+ cells generated from Gata1s-knockin progenitors, their expression
led to a significant reduction in the more mature CD42 fraction.
Serial replating assays revealed that overexpression of ERG or FLI-1
immortalized Gata1-knockdown and Gata1s knockin, but not wild-type,
fetal liver progenitors. Immortalization was accompanied by activation
of the JAK/STAT pathway, commonly seen in megakaryocytic malignancies.
These findings provide evidence for synergy between alterations in
GATA-1 and overexpression of ETS proteins in aberrant megakaryopoiesis.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/14/3337}
}
@ARTICLE{Stankovic2004,
author = {Stankovic, Konstantina and Rio, Carlos and Xia, Anping and Sugawara,
Mitsuru and Adams, Joe C. and Liberman, M. Charles and Corfas, Gabriel},
title = {Survival of Adult Spiral Ganglion Neurons Requires erbB Receptor
Signaling in the Inner Ear},
journal = {J. Neurosci.},
year = {2004},
volume = {24},
pages = {8651--8661},
number = {40},
month = oct,
abstract = {Degeneration of cochlear sensory neurons is an important cause of
hearing loss, but the mechanisms that maintain the survival of adult
cochlear sensory neurons are not clearly defined. We now provide
evidence implicating the neuregulin (NRG)-erbB receptor signaling
pathway in this process. We found that NRG1 is expressed by spiral
ganglion neurons (SGNs), whereas erbB2 and erbB3 are expressed by
supporting cells of the organ of Corti, suggesting that these molecules
mediate interactions between these cells. Transgenic mice in which
erbB signaling in adult supporting cells is disrupted by expression
of a dominant-negative erbB receptor show severe hearing loss and
80% postnatal loss of type-I SGNs without concomitant loss of the
sensory cells that they contact. Quantitative RT-PCR analysis of
neurotrophic factor expression shows a specific downregulation in
expression of neurotrophin-3 (NT3) in the transgenic cochleas before
the onset of neuronal death. Because NT3 is critical for survival
of type I SGNs during development, these results suggest that it
plays similar roles in the adult. Together, the data indicate that
adult cochlear supporting cells provide critical trophic support
to the neurons, that survival of postnatal cochlear sensory neurons
depends on reciprocal interactions between neurons and supporting
cells, and that these interactions are mediated by NRG and neurotrophins.},
url = {http://www.jneurosci.org/cgi/content/abstract/24/40/8651}
}
@ARTICLE{Stankovic2010,
author = {Stankovic, Konstantina M. and Adachi, Osamu and Tsuji, Kunikazu and
Kristiansen, Arthur G. and Adams, Joe C. and Rosen, Vicki and McKenna,
Michael J.},
title = {Differences in gene expression between the otic capsule and other
bones},
journal = {Hearing Research},
year = {2010},
volume = {265},
pages = {83--89},
number = {1-2},
month = jun,
abstract = {Our long term goal is to understand the molecular pathology of otosclerosis
and to develop better forms of therapy. Toward this goal, the current
study focused on characterizing the molecular factors responsible
for the unique biological features of the otic capsule: its minimal
rate of remodeling, and lack of healing capacity when fractured.
We compared expression levels of 62 genes involved in bone metabolism
between the adult murine otic capsule and the tibia and parietal
bones; the latter exemplify bones formed by endochondral and intramembranous
ossification, respectively. Gene expression levels were measured
using real-time quantitative RT-PCR and analyzed using tools of bioinformatics.
Expression patterns of key genes were verified with in situ hybridization.
The molecular profile of the otic capsule was distinctly different
from that of the tibia and parietal bone. Genes found to be most
characteristic of the otic capsule were: osteoprotegerin (opg), bone
morphogenetic protein receptor 1b (bmpr1b) and bone morphogenetic
protein 3 (bmp3). Expression levels were high for opg and bmpr1b,
and minimal for bmp3 within the otic capsule. We concluded that opg
and bmpr1b likely play important roles in inhibition of remodeling
within the otic capsule.},
issn = {0378-5955},
keywords = {Otic capsule, opg, Bmpr1b, Otosclerosis},
url = {http://www.sciencedirect.com/science/article/B6T73-4YBKG3T-2/2/23c42cebea88106e23f47a7659bf3645}
}
@ARTICLE{Stankovic2003,
author = {Stankovic, Konstantina M. and Corfas, Gabriel},
title = {Real-time quantitative RT-PCR for low-abundance transcripts in the
inner ear: analysis of neurotrophic factor expression},
journal = {Hearing Research},
year = {2003},
volume = {185},
pages = {97--108},
number = {1-2},
month = nov,
abstract = {Real-time quantitative reverse transcription-PCR is a highly sensitive
technology that allows high throughput quantification of gene expression.
Application of this technique to the inner ear is potentially very
important, but is not straightforward because tissue harvesting can
be challenging, RNA yield from individual inner ears is low, and
cDNA synthesis from scant RNA can be inefficient. To overcome these
challenges, we tested many parameters and reagents, and developed
an approach to reliably quantitate small changes in low-abundance
transcripts. Using this technique we demonstrate the presence and
quantify amounts of the neurotrophic factors neurotrophin 3 (NT-3),
brain-derived neurotrophic factor (BDNF) and glial cell-line-derived
neurotrophic factor (GDNF), in the cochlea and vestibular end organs
of postnatal murine inner ear (P26). We show that out of the factors
tested, BDNF is the only one differentially expressed between the
cochlea and vestibular end organs, being 23.4±0.3 times more abundant
in the vestibular end organs. Within the cochlea, GDNF gene expression
is 4.9±0.2 times greater than NT-3 expression. Within the combined
vestibular end organs, BDNF expression is 43.0±1.5 times greater
than NT-3 expression. Our results suggest that neurotrophic factors
continue to play a role in the postnatal inner ear, in addition to
their previously shown essential role during development.},
issn = {0378-5955},
keywords = {Real-time quantitative reverse transcription-polymerase chain reaction,
Neurotrophin 3, Brain-derived neurotrophic factor, Glial cell-line-derived
neurotrophic factor, Postnatal inner ear},
url = {http://www.sciencedirect.com/science/article/B6T73-49W204T-2/2/5d0518ff710e46189ceb02fc43dc8664}
}
@ARTICLE{Stankovic2008,
author = {Stankovic, Konstantina M. and Goldsztein, Hernan and Reh, Douglas
D. and Platt, Michael P. and Metson, Ralph},
title = {Gene Expression Profiling of Nasal Polyps Associated With Chronic
Sinusitis and Aspirin-Sensitive Asthma},
journal = {The Laryngoscope},
year = {2008},
volume = {118},
pages = {881--889},
number = {5},
abstract = {Abstract 10.1097/MLG.0b013e31816b4b6f.abs Objective: To identify genes
whose expression is most characteristic of chronic rhinosinusitis
and aspirin-sensitive asthma through genome-wide transcriptional
profiling of nasal polyp tissue. Study Design: Prospective, controlled
study conducted at a tertiary care institution. Methods: Thirty genome-wide
expression microarrays were used to compare nasal polyp tissue from
patients with chronic rhinosinusitis alone (CRS, n = 10) or chronic
rhinosinusitis and a history of aspirin-sensitive asthma (ASA, n
= 10) to normal sinonasal mucosa from patients who underwent surgery
for non-sinus related conditions (controls, n = 10). Genes found
to be most characteristic of each polyp phenotype, as determined
from bioinformatic analyses, were validated using real-time quantitative
polymerase chain reaction (RT-PCR) and immunohistochemistry in different
patient sets. Results: The transcriptional signature of the control
mucosa was distinctly different from that of either polyp phenotype.
Genes most characteristic of the CRS phenotype included two upregulated
genes—met proto-oncogene (MET) and protein phosphatase 1 regulatory
subunit 9B (PPP1R9B)—and two downregulated genes— prolactin-induced
protein (PIP) and zinc alpha2-glycoprotein (AZGP1). The gene most
characteristic of the ASA phenotype was periostin (POSTN), which
was upregulated relative to controls. Differences between the CRS
and ASA phenotypes were associated with alterations in the 6p22,
22q13, and 1q23 chromosomal regions. Conclusions: Nasal polyps appear
to have characteristic transcriptional signatures compared to normal
sinonasal mucosa. The five genes identified in this study likely
play roles in the pathogenesis of polyps associated with CRS and
ASA, and are therefore attractive targets for novel medical therapies
for these common debilitating diseases.},
issn = {1531-4995},
keywords = {Sinonasal polyposis, chronic rhinosinusitis, sinusitis, asthma, triad
asthma, aspirin-sensitive asthma, microarray, periostin, POSTN, c-Met,
met proto-oncogene, prolactin-induced protein, zinc alpha2-glycoprotein,
protein phosphatase 1},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1097/MLG.0b013e31816b4b6f}
}
@ARTICLE{Stanley2011,
author = {Stanley, Erin L. and Johnston, Daniel S. and Fan, Jinjiang and Papadopoulos,
Vassilios and Chen, Haolin and Ge, Ren-Shan and Zirkin, Barry R.
and Jelinsky, Scott A.},
title = {Stem Leydig Cell Differentiation: Gene Expression During Development
of the Adult Rat Population of Leydig Cells},
journal = {Biol Reprod},
year = {2011},
volume = {85},
pages = {1161-1166},
number = {6},
abstract = {Leydig cells are the testosterone-producing cells in the adult male.
Adult Leydig cells (ALCs) develop from stem Leydig cells (SLCs) through
at least two intermediate cells, progenitor Leydig cells (PLCs) and
immature Leydig cells (ILCs). Microarray gene expression was used
to identify the transcriptional changes that occur with the differentiation
of SLCs to PLCs and, thus, with the entry of SLCs into the Leydig
cell lineage; to comprehensively examine differentiation through
the development of ALCs; and to relate the pattern of gene expression
in SLCs to that in a well-established stem cell, bone marrow stem
cells (BSCs). We show that the pattern of gene expression by SLCs
was more similar to the expression by BSCs, an established stem cell
outside the male reproductive tract, than to any of the cells in
the Leydig cell developmental lineage. These results indicated that
the SLCs have many of the molecular characteristics of other stem
cells. Pathway analysis indicated that development of Leydig cells
from SLCs to PLCs was associated with decreased expression of genes
related to adhesion and increased expression of genes related to
steroidogenesis. Gene expression changes between PLCs and ILCs and
between ILCs and ALCs were relatively minimal, suggesting that these
cells are highly similar. In contrast, gene expression changes between
SLCs and ALCs were quite distinct.},
doi = {10.1095/biolreprod.111.091850},
eprint = {http://www.biolreprod.org/cgi/reprint/85/6/1161.pdf},
url = {http://www.biolreprod.org/cgi/content/abstract/85/6/1161}
}
@ARTICLE{Stanley2005,
author = {Stanley, Keith K. and Szewczuk, Elektra},
title = {Multiplexed tandem PCR: gene profiling from small amounts of RNA
using SYBR Green detection},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {e180--},
number = {20},
month = nov,
abstract = {Multiplexed tandem PCR (MT-PCR) is a process for highly multiplexed
gene expression profiling. In the first step, multiple primer pairs
are added to the RNA to be analysed together with reverse transcriptase
and Taq DNA polymerase. Following reverse transcription, the multiplexed
amplicons are simultaneously amplified for a small number of cycles
so as to avoid competition between amplicons. The reaction product
is then diluted and analysed in multiple individual PCRs using primers
nested inside the primers used for the multiplexed amplification.
As the second PCR uses a template enriched in the amplicons of interest,
the conditions can be optimized to significantly reduce primer dimer'
formation allowing SYBR Green chemistry to be used for quantification.
MT-PCR can be configured for as little as 10 pg RNA (equivalent to
a single mammalian cell) and works well with RNA extracted from archival
formalin-fixed paraffin-embedded sections. We illustrate MT-PCR with
gene expression profiles of breast cancer cell lines.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/20/e180}
}
@ARTICLE{Stansberg2011,
author = {Stansberg, Christine and Ersland, Kari and van der Valk, Paul and
Steen, Vidar},
title = {Gene expression in the rat brain: High similarity but unique differences
between frontomedial-, temporal- and occipital cortex},
journal = {BMC Neuroscience},
year = {2011},
volume = {12},
pages = {15},
number = {1},
abstract = {BACKGROUND:The six-layered neocortex of the mammalian brain may appear
largely homologous, but is in reality a modular structure of anatomically
and functionally distinct areas. However, global gene expression
seems to be almost identical across the cerebral cortex and only
a few genes have so far been reported to show regional enrichment
in specific cortical areas.RESULTS:In the present study on adult
rat brain, we have corroborated the strikingly similar gene expression
among cortical areas. However, differential expression analysis has
allowed for the identification of 30, 24 and 11 genes enriched in
frontomedial -, temporal- or occipital cortex, respectively. A large
proportion of these 65 genes appear to be involved in signal transduction,
including the ion channel Fxyd6, the neuropeptide Grp and the nuclear
receptor Rorb. We also find that the majority of these genes display
increased expression levels around birth and show distinct preferences
for certain cortical layers and cell types in rodents.CONCLUSIONS:Since
specific patterns of expression often are linked to equally specialised
biological functions, we propose that these cortex sub-region enriched
genes are important for proper functioning of the cortical regions
in question.},
doi = {10.1186/1471-2202-12-15},
issn = {1471-2202},
pubmedid = {21269499},
url = {http://www.biomedcentral.com/1471-2202/12/15}
}
@ARTICLE{Stansfield2009,
author = {Stansfield, William E. and Andersen, Nancy M. and Tang, Ru-Hang and
Selzman, Craig H.},
title = {Periostin Is a Novel Factor in Cardiac Remodeling After Experimental
and Clinical Unloading of the Failing Heart},
journal = {The Annals of Thoracic Surgery},
year = {2009},
volume = {88},
pages = {1916--1921},
number = {6},
month = dec,
abstract = {Background Maladaptive left ventricular hypertrophy (LVH) remains
a prevalent and highly morbid condition associated with end-stage
heart disease. Originally evaluated in the context of bone development,
periostin is important in endocardial cushion formation and has recently
been implicated in heart failure. Because of its potential role in
cardiovascular development, we sought to establish the role of periostin
after relief of pressure overload in animal and human models.Methods
Pressure overload induction of LVH was performed by minimally invasive
aortic arch banding of C57Bl6 mice. Bands were removed 1 month later
to allow regression. Cardiac tissue was procured in paired samples
of patients receiving LV assist devices (LVAD), with subsequent reanalysis
at the time of explant for transplantation.Results One week after
debanding, heart weight/body weight ratios and echocardiography confirmed
decreased LV mass relative to hypertrophied animals. Gene and protein
expression of periostin was measured by real-time polymerase chain
reaction and Western blot, and was similarly decreased compared with
LVH mice. Immunohistochemical localization of periostin showed it
was exclusively in the extracellular matrix of the myocardium. The
decrease in periostin with pressure relief paralleled changes in
interstitial fibrosis observed by picrosirius red staining. Corroborating
the murine data, periostin expression was significantly reduced after
LVAD-afforded pressure relief in patients.Conclusions Periostin is
closely associated with pressure overload-induced LVH and LVH regression
in both animal and human models. The magnitude of expression changes
and the consistent nature of these changes indicate that periostin
may be a mediator of cardiac remodeling.},
issn = {0003-4975},
url = {http://www.sciencedirect.com/science/article/B6T11-4XRHS3G-1G/2/e1918858b65903ef473508eaf67f584c}
}
@ARTICLE{Stansfield2009a,
author = {Stansfield, William E. and Charles, Peter C. and Tang, Ru-hang and
Rojas, Mauricio and Bhati, Rajendra and Moss, Nancy C. and Patterson,
Cam and Selzman, Craig H.},
title = {Regression of pressure-induced left ventricular hypertrophy is characterized
by a distinct gene expression profile},
journal = {J. Thorac. Cardiovasc. Surg.},
year = {2009},
volume = {137},
pages = {232--238},
number = {1},
month = jan,
abstract = {ObjectiveLeft ventricular hypertrophy is a highly prevalent and robust
predictor of cardiovascular morbidity and mortality. Existing studies
have finely detailed mechanisms involved with its development, yet
clinical translation of these findings remains unsatisfactory. We
propose an alternative strategy focusing on mechanisms of left ventricular
hypertrophy regression rather than its progression and hypothesize
that left ventricular hypertrophy regression is associated with a
distinct genomic profile. MethodsMinimally invasive transverse arch
banding and debanding (or their respective sham procedures) were
performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed
physiologically by means of transthoracic echocardiographic analysis,
structurally by means of histology, and molecularly by means of real-time
polymerase chain reaction. Mouse hearts were genomically analyzed
with Agilent (Santa Clara, Calif) mouse 44k developmental gene chips.
ResultsCompared with control animals, animals banded for 28 days
had a robust hypertrophic response, as determined by means of heart
weight/body weight ratio, histologic analysis, echocardiographic
analysis, and fetal gene expression. These parameters were reversed
within 1 week of debanding. Whole-genome arrays on left ventricular
tissue revealed 288 genes differentially expressed during progression,
265 genes differentially expressed with regression, and only 23 genes
shared by both processes. Signaling-related expression patterns were
more prevalent with regression rather than the structure-related
patterns associated with left ventricular hypertrophy progression.
In addition, regressed hearts showed comparatively more changes in
energy metabolism and protein production. ConclusionsThis study demonstrates
an effective model for characterizing left ventricular hypertrophy
and reveals that regression is genomically distinct from its development.
Further examination of these expression profiles will broaden our
understanding of left ventricular hypertrophy and provide a novel
therapeutic paradigm focused on promoting regression of left ventricular
hypertrophy and not just halting its progression.},
url = {http://jtcs.ctsnetjournals.org/cgi/content/abstract/137/1/232}
}
@ARTICLE{Stanton2009,
author = {Stanton, Brynne C. and Giles, Steven S. and Kruzel, Emilia K. and
Warren, Christopher L. and Ansari, Aseem Z. and Hull, Christina M.},
title = {Cognate Site Identifier analysis reveals novel binding properties
of the Sex Inducer homeodomain proteins of Cryptococcus neoformans},
journal = {Molecular Microbiology},
year = {2009},
volume = {72},
pages = {1334--1347},
number = {6},
abstract = {Summary Homeodomain proteins function in fungi to specify cell types
and control sexual development. In the meningoencephalitis-causing
fungal pathogen Cryptococcus neoformans, sexual development leads
to the production of spores (suspected infectious particles). Sexual
development is controlled by the homeodomain transcription factors
Sxi1α and Sxi2a, but the mechanism by which they act is unknown.
To understand how the Sxi proteins regulate development, we characterized
their binding properties in vitro, showing that Sxi2a does not require
a partner to bind DNA with high affinity. We then utilized a novel
approach, Cognate Site Identifier (CSI) arrays, to define a comprehensive
DNA-binding profile for Sxi2a, revealing a consensus sequence distinct
from those of other fungal homeodomain proteins. Finally, we show
that the homeodomains of both Sxi proteins are required for sexual
development, a departure from related fungi. Our findings support
a model in which Sxi1α and Sxi2a control sexual development in a
homeodomain-dependent manner by binding to DNA sequences that differ
from those defined in previously established fungal paradigms.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2009.06719.x}
}
@ARTICLE{Starkey2008,
author = {Starkey, Jean R. and Rebane, Aleksander K. and Drobizhev, Mikhail
A. and Meng, Fanqing and Gong, Aijun and Elliott, Aleisha and McInnerney,
Kate and Spangler, Charles W.},
title = {New Two-Photon Activated Photodynamic Therapy Sensitizers Induce
Xenograft Tumor Regressions after Near-IR Laser Treatment through
the Body of the Host Mouse},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6564--6573},
number = {20},
month = oct,
abstract = {Purpose: The aim of this study was to show that novel photodynamic
therapy (PDT) sensitizers can be activated by two-photon absorption
in the near-IR region of the spectrum and to show, for the first
time, that such activation can lead to tumor regressions at significant
tissue depth. These experiments also evaluated effects of high-energy
femtosecond pulsed laser irradiation on normal tissues and characterized
the response of xenograft tumors to our PDT protocols. Experimental
Design: Human small cell lung cancer (NCI-H69), non-small cell lung
cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced
in SCID mice. Irradiation of sensitized tumors was undertaken through
the bodies of tumor-bearing mice to give a treatment depth of 2 cm.
Posttreatment tumor regressions and histopathology were carried out
to determine the nature of the response to these new PDT agents.
Microarray expression profiles were conducted to assess the similarity
of responses to single and two-photon activated PDT. Results: Regressions
of all tumor types tested were seen. Histopathology was consistent
with known PDT effects, and no, or minimal, changes were noted in
irradiated normal tissues. Cluster analysis of microarray expression
profiling showed reproducible changes in transcripts associated with
apoptosis, stress, oxygen transport, and gene regulation. Conclusions:
These new PDT sensitizers can be used at a depth of 2 cm to produce
excellent xenograft regressions. The tumor response was consistent
with known responses to single-photon activated PDT. Experiments
in larger animals are warranted to determine the maximal achievable
depth of treatment.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/20/6564}
}
@ARTICLE{Starkey2010,
author = {Starkey, M. P. and Murphy, S.},
title = {Using lymph node fine needle aspirates for gene expression profiling
of canine lymphoma},
journal = {Veterinary and Comparative Oncology},
year = {2010},
volume = {8},
pages = {56--71},
number = {1},
abstract = {Conventional classification schemes for canine lymphomas do not discriminate
between phenotypically indistinct tumours that may exhibit differences
in behaviour. Transcriptional profiling has the potential to afford
objective clinically relevant stratification of canine lymphomas,
and its sensitivity means that prognostic assays could be performed
on tumour needle aspirates collected without anaesthesia. In this
pilot study, we compared the expression profiles derived from surgical
biopsies and fine needle aspirates of five lymphomas. The aspirates
yielded expression profiles of equivalent complexity and strong similarity
(median correlation Coefficient = 0.911) to those generated from
corresponding surgical biopsies. Differences in gene expression observed
between the two tissue sources suggest that the aspirates represent
a purer source of lymphocytes. Despite the absence of a standardized
sample collection protocol, the aspirates yielded expression profiles
of consistently high quality suggesting that they represent a robust
source of tumour tissue for a potential transcriptional profile-based
prognostic assay for canine lymphomas},
issn = {1476-5829},
keywords = {canine, fine needle aspirate, gene expression profiling, lymphoma},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1476-5829.2009.00205.x}
}
@ARTICLE{Starmans2009,
author = {Starmans, Maud H.W. and Zips, Daniel and Wouters, Bradly G. and Baumann,
Michael and Lambin, Philippe},
title = {The use of a comprehensive tumour xenograft dataset to validate gene
signatures relevant for radiation response},
journal = {Radiotherapy and Oncology},
year = {2009},
volume = {92},
pages = {417--422},
number = {3},
month = sep,
abstract = {Purpose To investigate the use of xenograft models in a novel gene
signature validation method using gene expression microarrays.Materials
and methods Gene expression profiles of ten human Head and Neck squamous
cell carcinomas (HNSCCs) were obtained. Several published prognostic
gene expression signatures were evaluated within this set. These
consisted of different radiotherapy relevant signatures (i.e. for
hypoxia, proliferation and [`]stemness'). Signatures were correlated
with various endpoints that have been determined in the ten different
xenograft models. These include immunohistochemical measures for
hypoxia and proliferation, volume doubling time (VDT) and local tumour
control after fractionated irradiation or after single dose irradiation
under clamp hypoxia.Results We found several significant correlations
between the published gene expression signatures and tumour parameters.
Several signatures, like the proliferation and wound signature correlated
with BrdU labelling index. Further a [`]stemness'-related gene signature
showed a strong negative correlation with hypoxic fraction.Conclusions
Simultaneous assessment of immunohistochemistry, in vivo tumour properties
and gene expression profiling in a comprehensive set of xenograft
models can be used to validate and potentially infer biological information
about prognostic gene signatures.},
booktitle = {Special Issue on Molecular and Experimental Radiobiology Including
papers from the 11th International Wolfsberg Meeting on Molecular
Radiation Biology/Oncology},
issn = {0167-8140},
keywords = {Gene expression signature, Human tumour xenograft, Proliferation,
Hypoxia, Stemness, Immunohistochemistry},
url = {http://www.sciencedirect.com/science/article/B6TBY-4WSBD6C-1/2/acc6b2ee127d247f7537cdf24797773f}
}
@ARTICLE{Starossom2011,
author = {Sarah C. Starossom and Jaime Imitola and Yue Wang and Li Cao and
Samia J. Khoury},
title = {Subventricular zone microglia transcriptional networks},
journal = {Brain, Behavior, and Immunity},
year = {2011},
volume = {25},
pages = {991 - 999},
number = {5},
note = {Special Issue: Adaptive Immunity in the Central Nervous
System Function},
abstract = {Microglia play an important role in inflammatory diseases of the central
nervous system. There is evidence of microglial diversity with distinct
phenotypes exhibiting either neuroprotection and repair or neurotoxicity.
However the precise molecular mechanisms underlying this diversity
are still unknown.
Using a model of experimental autoimmune encephalomyelitis (EAE) we
performed transcriptional profiling of isolated subventricular zone
microglia from the acute and chronic disease phases of EAE. We found
that microglia exhibit disease phase specific gene expression signatures,
that correspond to unique gene ontology functions and genomic networks.
Our data demonstrate for the first time, distinct transcriptional
networks of microglia activation in vivo, that suggests a role as
mediators of injury or repair.},
doi = {10.1016/j.bbi.2010.11.002},
issn = {0889-1591},
keywords = {EAE},
url = {http://www.sciencedirect.com/science/article/pii/S0889159110005337}
}
@ARTICLE{Stasakova2005,
author = {Stasakova, Jana and Ferko, Boris and Kittel, Christian and Sereinig,
Sabine and Romanova, Julia and Katinger, Hermann and Egorov, Andrej},
title = {Influenza A mutant viruses with altered NS1 protein function provoke
caspase-1 activation in primary human macrophages, resulting in fast
apoptosis and release of high levels of interleukins 1{beta} and
18},
journal = {J. Gen. Virol.},
year = {2005},
volume = {86},
pages = {185--195},
number = {1},
month = jan,
abstract = {Several NS1 mutant viruses of human influenza A/PR/8/34 (H1N1) virus
were tested for their ability to induce pro-inflammatory cytokines
in primary human macrophages. The findings revealed a pronounced
difference in the virus-induced cytokine pattern, depending on the
functionality of the NS1 protein-encoded domains. The PR8/NS1-125
mutant virus, which encodes the first 125 aa of the NS1 protein,
thus lacking the C-terminal domains, induced significantly higher
amounts of beta interferon, interleukin (IL) 6, tumour necrosis factor
alpha and CCL3 (MIP-1{alpha}) when compared with the A/PR/8/34 wild-type
virus. However, this mutant virus was as efficient as wild-type virus
in the inhibition of IL1{beta} and IL18 release from infected macrophages.
Another group of viral mutants either lacking or possessing non-functional
RNA-binding and dimerization domains induced 10-50 times more biologically
active IL1{beta} and five times more biologically active IL18 than
the wild-type or PR8/NS1-125 viruses. The hallmark of infection with
this group of mutant viruses was the induction of rapid apoptosis
in infected macrophages, which correlated with the enhanced activity
of caspase-1. These results indicated that the NS1 protein, through
the function of its N-terminal domains, might control caspase-1 activation,
thus repressing the maturation of pro-IL1{beta}-, pro-IL18- and caspase-1-dependent
apoptosis in infected primary human macrophages.},
url = {http://vir.sgmjournals.org/cgi/content/abstract/86/1/185}
}
@ARTICLE{Stasiewicz2011,
author = {Stasiewicz, Matthew J. and Wiedmann, Martin and Bergholz, Teresa
M.},
title = {The Transcriptional Response of Listeria monocytogenes during Adaptation
to Growth on Lactate and Diacetate Includes Synergistic Changes That
Increase Fermentative Acetoin Production},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {5294-5306},
number = {15},
abstract = {The organic acids lactate and diacetate are commonly used in combination
in ready-to-eat foods because they show synergistic ability to inhibit
the growth of Listeria monocytogenes. Full-genome microarrays were
used to investigate the synergistic transcriptomic responses of two
L. monocytogenes strains, H7858 (serotype 4b) and F6854 (serotype
1/2a), to these two organic acids under conditions representing osmotic
and cold stress encountered in foods. Strains were exposed to brain
heart infusion (BHI) broth at 7{degrees}C with 4.65% water-phase
(w.p.) NaCl at pH 6.1 with (i) 2% w.p. potassium lactate, (ii) 0.14%
w.p. sodium diacetate, (iii) the combination of both at the same
levels, or (iv) no organic acids as a control. RNA was extracted
8 h after exposure, during lag phase, to capture gene transcription
changes during adaptation to the organic acid stress. Significant
differential transcription of 1,041 genes in H7858 and 640 genes
in F6854 was observed in at least one pair of the 4 different treatments.
The effects of combined treatment with lactate and diacetate included
(i) synergistic transcription differences for 474 and 209 genes in
H7858 and F6854, respectively, (ii) differential transcription of
genes encoding cation transporters and ABC transporters of metals,
and (iii) altered metabolism, including induction of a nutrient-limiting
stress response, reduction of menaquinone biosynthesis, and a shift
from fermentative production of acetate and lactate to energetically
less favorable, neutral acetoin. These data suggest that additional
treatments that interfere with cellular energy generation processes
could more efficiently inhibit the growth of L. monocytogenes.},
doi = {10.1128/AEM.02976-10},
eprint = {http://aem.asm.org/cgi/reprint/77/15/5294.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/15/5294}
}
@ARTICLE{Stauffer2008,
author = {Stauffer, Brian L and Kushner, Erich J. and Wulfman, Ted and Zeller,
Thomas and Sobus, Rebecca and Westby, Christian M.},
title = {Transcriptional Regulation of β2-Microglobulin Demonstrated Via
a Novel Genomic and Proteomic Analysis of Percutaneously Collected
Peripheral Atheroma},
journal = {Clinical and Translational Science},
year = {2008},
volume = {1},
pages = {240--244},
number = {3},
issn = {1752-8062},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1752-8062.2008.00071.x}
}
@ARTICLE{Stauffer2010,
author = {Stauffer, Eva and Westermann, Alexander and Wagner, Gabriele and
Wachter, Andreas},
title = {Polypyrimidine tract-binding protein homologues from Arabidopsis
underlie regulatory circuits based on alternative splicing and downstream
control},
journal = {The Plant Journal},
year = {2010},
volume = {64},
pages = {243--255},
number = {2},
abstract = {Summary Alternative splicing (AS) of precursor mRNAs is a widespread
phenomenon in plants; however, many questions, especially regarding
its regulation and functional implications, remain to be elucidated.
In vertebrates, polypyrimidine tract-binding proteins (PTBs) have
been identified as key splicing factors influencing splice site selection
and orchestrating coordinated splicing programmes during developmental
processes. Here, we analysed three PTB homologues from Arabidopsis
thaliana and provide evidence for their gene regulatory potential
based on AS and a splicing-independent mechanism. Our data reveal
that Arabidopsis PTB homologues are subject to extensive auto- and
cross-regulation via AS-coupled nonsense-mediated decay, thereby
establishing a basis for interlinking their expression. Furthermore,
the multiple modes of action of Arabidopsis PTB homologues are reflected
in their subcellular localization in the nucleus, cytosol and processing
bodies. This work provides insight into the regulation of AS in plants
and highlights the regulatory potential of the multifunctional plant
PTB homologues, which might have important implications in diverse
biological processes.},
issn = {1365-313X},
keywords = {polypyrimidine, splicing, nonsense-mediated decay, P-body, gene regulation,
Arabidopsis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04321.x}
}
@ARTICLE{Stavang2007,
author = {Stavang, Jon Anders and Junttila, Olavi and Moe, Roar and Olsen,
Jorunn E.},
title = {Differential temperature regulation of GA metabolism in light and
darkness in pea},
journal = {J. Exp. Bot.},
year = {2007},
volume = {58},
pages = {3061--3069},
number = {11},
month = aug,
abstract = {In greenhouse production of a number of flowering plant species, a
short diurnal temperature drop in the morning is commonly used to
reduce stem elongation. Earlier studies of pea (Pisum sativum) exposed
to different combinations of day and night temperature, indicate
that light, temperature, and gibberellin (GA) interact in the control
of stem elongation. However, the mechanisms behind the effects of
short-term temperature drops and differential sensitivity depending
on the timing of the drop treatment have not been reported. Here,
the involvement of GA metabolism in this has been investigated by
exposing pea to short-term temperature drops in light or darkness.
A 2 h temperature drop from 21 {degrees}C to 13 {degrees}C in the
middle of the light period rapidly reduced the rate of stem elongation
temporarily by 55% and increased mRNA levels of the GA-deactivation
gene PsGA2ox2 by 2-fold within 30 min and up to 4-fold within 1.5
h. GA1 levels were reduced by 36% after a 3-4 h time lag. A temperature
drop in the night reduced stem elongation by 27%, but had no effect
on transcript levels of PsGA2ox2. Instead, steady-state expression
of the GA-biosynthesis genes NA, PsGA20ox1, and PsGA3ox1 was slightly
stimulated, but there was no effect on GA1 level. In conclusion,
the effect of a temperature drop on GA metabolism in pea is qualitatively
different in light and dark. Light is required for deactivation of
GA1 resulting from increased expression of PsGA2ox2. This suggests
that GA-metabolism is a component in the short-term adaptation to
changes in ambient temperature and putatively in low temperature-light
stress responses.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/58/11/3061}
}
@ARTICLE{Stavang2005,
author = {Stavang, Jon Anders and Lindgard, Bente and Erntsen, Arild and Lid,
Stein Erik and Moe, Roar and Olsen, Jorunn E.},
title = {Thermoperiodic Stem Elongation Involves Transcriptional Regulation
of Gibberellin Deactivation in Pea},
journal = {Plant Physiology},
year = {2005},
volume = {138},
pages = {2344--2353},
number = {4},
month = aug,
abstract = {The physiological basis of thermoperiodic stem elongation is as yet
poorly understood. Thermoperiodic control of gibberellin (GA) metabolism
has been suggested as an underlying mechanism. We have investigated
the influence of different day and night temperature combinations
on GA levels, and diurnal steady-state expression of genes involved
in GA biosynthesis (LS, LH, NA, PSGA20ox1, and PsGA3ox1) and GA deactivation
(PsGA2ox1 and PsGA2ox2), and related this to diurnal stem elongation
in pea (Pisum sativum L. cv Torsdag). The plants were grown under
a 12-h light period with an average temperature of 17{degrees}C.
A day temperature/night temperature combination of 13{degrees}C/21{degrees}C
reduced stem elongation after 12 d by 30% as compared to 21{degrees}C/13{degrees}C.
This was correlated with a 55% reduction of GA1. Although plant height
correlated with GA1 content, there was no correlation between diurnal
growth rhythms and GA1 content. NA, PsGA20ox1, and PsGA2ox2 showed
diurnal rhythms of expression. PsGA2ox2 was up-regulated in 13{degrees}C/21{degrees}C
(compared to 21{degrees}C/13{degrees}C), at certain time points,
by up to 19-fold. Relative to PsGA2ox2, the expression of LS, LH,
NA, PSGA20ox1, PsGA3ox1, and PsGA2ox1 was not or only slightly affected
by the different temperature treatments. The sln mutant having a
nonfunctional PsGA2ox1 gene product showed the same relative stem
elongation response to temperature as the wild type. This supports
the importance of PsGA2ox2 in mediating thermoperiodic stem elongation
responses in pea. We present evidence for an important role of GA
catabolism in thermoperiodic effect on stem elongation and conclude
that PsGA2ox2 is the main mediator of this effect in pea.},
url = {http://www.plantphysiol.org/cgi/content/abstract/138/4/2344}
}
@ARTICLE{Stead2006,
author = {Stead, John D. H. and Neal, Charles and Meng, Fan and Wang, Yongjia
and Evans, Simon and Vazquez, Delia M. and Watson, Stanley J. and
Akil, Huda},
title = {Transcriptional Profiling of the Developing Rat Brain Reveals That
the Most Dramatic Regional Differentiation in Gene Expression Occurs
Postpartum},
journal = {J. Neurosci.},
year = {2006},
volume = {26},
pages = {345--353},
number = {1},
month = jan,
abstract = {Neural development involves the expression of ensembles of regulatory
genes that control the coordinate and region-specific expression
of a host of other genes, resulting in the unique structure, connectivity,
and function of each brain region. Although the role of some specific
genes in neural development has been studied in detail, we have no
global view of the orchestration of spatial and temporal aspects
of gene expression across multiple regions of the developing brain.
To this end, we used transcriptional profiling to examine expression
levels of 9955 genes in the hypothalamus, hippocampus, and frontal
cortex across seven stages of postnatal development and up to four
stages of prenatal development in individual male rats (six per group).
The results reveal dramatic changes across development in >97% of
the neurally expressed genes. They also uncover a surprising degree
of regional differentiation occurring after birth and through the
first 2 weeks of life. Cluster analysis identifies 20 clusters of
transcripts enriched in genes related to particular functions, such
as DNA metabolism, nuclear function, synaptic vesicle transport,
myelination, and neuropeptide hormone activity. Thus, groups of genes
with related functions change in the brain at specific times, possibly
marking critical periods for each function. These findings can broadly
serve as a backdrop for studying the role of individual genes in
neural development. They also underscore the importance of early
postnatal life in the rat, which corresponds to late gestation in
the human, as a critical late phase of neural organization and differentiation,
even in subcortical regions.},
url = {http://www.jneurosci.org/cgi/content/abstract/26/1/345}
}
@ARTICLE{Stead2011,
author = {Stead, Mark B. and Marshburn, Sarah and Mohanty, Bijoy K. and Mitra,
Joydeep and Castillo, Lourdes Pena and Ray, Debashish and van Bakel,
Harm and Hughes, Timothy R. and Kushner, Sidney R.},
title = {Analysis of Escherichia coli RNase E and RNase III activity in vivo
using tiling microarrays},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {3188--3203},
number = {8},
month = apr,
abstract = {Tiling microarrays have proven to be a valuable tool for gaining insights
into the transcriptomes of microbial organisms grown under various
nutritional or stress conditions. Here, we describe the use of such
an array, constructed at the level of 20 nt resolution for the Escherichia
coli MG1655 genome, to observe genome-wide changes in the steady-state
RNA levels in mutants defective in either RNase E or RNase III. The
array data were validated by comparison to previously published results
for a variety of specific transcripts as well as independent northern
analysis of additional mRNAs and sRNAs. In the absence of RNase E,
60% of the annotated coding sequences showed either increases or
decreases in their steady-state levels. In contrast, only 12% of
the coding sequences were affected in the absence of RNase III. Unexpectedly,
many coding sequences showed decreased abundance in the RNase E mutant,
while more than half of the annotated sRNAs showed changes in abundance.
Furthermore, the steady-state levels of many transcripts showed overlapping
effects of both ribonucleases. Data are also presented demonstrating
how the arrays were used to identify potential new genes, RNase III
cleavage sites and the direct or indirect control of specific biological
pathways.},
comment = {10.1093/nar/gkq1242},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/8/3188}
}
@ARTICLE{Stearman2008,
author = {Stearman, Robert S. and Dwyer-Nield, Lori and Grady, Michael C. and
Malkinson, Alvin M. and Geraci, Mark W.},
title = {A Macrophage Gene Expression Signature Defines a Field Effect in
the Lung Tumor Microenvironment},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {34--43},
number = {1},
month = jan,
abstract = {One area of intensive investigation is to understand complex cellular
and signaling interactions in the tumor microenvironment. Using a
novel, although straightforward, microarray approach, we defined
a gene expression signature from the lung tumor microenvironment
in the murine A/J-urethane model of human lung adenocarcinoma. The
tumor microenvironment is reflected by the composition of the cell
types present and alterations in mRNA levels, resulting in a "Field
Effect" around the tumor. The genes composing the Field Effect expression
signature include proteases and their inhibitors, inflammation markers,
and immune signaling molecules. By several criteria, the Field Effect
expression signature can be attributed to the macrophage lineage,
suggesting a qualitative change in the expression pattern of tumor-associated
macrophages (TAM) observed in lung tumors. The protein expression
levels for a number of Field Effect genes were verified by Western
blot analysis of lung homogenates, and for their expression in macrophages
and parenchymal cells outside of the tumors by immunohistochemistry.
In addition, the Field Effect expression signature was used to classify
bronchoalveolar lavage (BAL) cells from tumor-bearing or age-matched
control mice. Using a variety of statistical measures, the Field
Effect expression signature correctly classified the BAL cells >94%
of the time. Finally, the protein levels for several Field Effect
genes were higher in cell-free BAL fluid, indicating they may be
secreted by the TAMs. This work suggests that TAMs generate a unique
gene expression signature within the tumor microenvironment, and
this signature could potentially be used for identifying lung cancer
from BAL cells and/or fluid. [Cancer Res 2008;68(1):34-43]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/1/34}
}
@ARTICLE{Stearman2005,
author = {Stearman, Robert S. and Dwyer-Nield, Lori and Zerbe, Laura and Blaine,
Stacy A. and Chan, Zeng and Bunn, Paul A., Jr. and Johnson, Gary
L. and Hirsch, Fred R. and Merrick, Daniel T. and Franklin, Wilbur
A. and Baron, Anna E. and Keith, Robert L. and Nemenoff, Raphael
A. and Malkinson, Alvin M. and Geraci, Mark W.},
title = {Analysis of Orthologous Gene Expression between Human Pulmonary Adenocarcinoma
and a Carcinogen-Induced Murine Model},
journal = {Am. J. Pathol.},
year = {2005},
volume = {167},
pages = {1763--1775},
number = {6},
month = dec,
abstract = {Human adenocarcinoma (AC) is the most frequently diagnosed human lung
cancer, and its absolute incidence is increasing dramatically. Compared
to human lung AC, the A/J mouse-urethane model exhibits similar histological
appearance and molecular changes. We examined the gene expression
profiles of human and murine lung tissues (normal or AC) and compared
the two species' datasets after aligning [~]7500 orthologous genes.
A list of 409 gene classifiers (P value <0.0001), common to both
species (joint classifiers), showed significant, positive correlation
in expression levels between the two species. A number of previously
reported expression changes were recapitulated in both species, such
as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly,
joint classifiers in angiogenesis were uniformly down-regulated in
tumor tissues. The eicosanoid pathway enzymes prostacyclin synthase
(PGIS) and inducible prostaglandin E2 synthase (PGES) were joint
classifiers that showed opposite effects in lung AC (PGIS down-regulated;
PGES up-regulated). Finally, tissue microarrays identified the same
protein expression pattern for PGIS and PGES in 108 different non-small
cell lung cancer biopsies, and the detection of PGIS had statistically
significant prognostic value in patient survival. Thus, the A/J mouse-urethane
model reflects significant molecular details of human lung AC, and
comparison of changes in orthologous gene expression may provide
novel insights into lung carcinogenesis.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/167/6/1763}
}
@ARTICLE{Stearman2007,
author = {Stearman, Robert S. and Grady, Michael C. and Nana-Sinkam, Patrick
and Varella-Garcia, Marileila and Geraci, Mark W.},
title = {Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase
Promoter in Lung Cancer Cell Lines},
journal = {Mol. Cancer Res.},
year = {2007},
volume = {5},
pages = {295--308},
number = {3},
month = mar,
abstract = {The importance of the arachidonic acid pathway has been established
in colon and lung cancers, as well as in inflammatory diseases. In
these diseases, prostacyclin I2 (PGI2) and prostaglandin E2 (PGE2)
are thought to have antagonistic activities, with PGI2 exerting anti-inflammatory
and antiproliferative activities, whereas PGE2 is proinflammatory
and antiapoptotic. In human lung cancer, prostacyclin synthase (PGIS)
and PGI2 are down-regulated, whereas PGE2 synthase (PGES) and PGE2
are up-regulated. Murine carcinogenesis models of human lung cancer
reciprocate the relationship between PGIS and PGES expression. PGIS-overexpressing
transgenic mice are protected from carcinogen- and tobacco smoke-induced
lung tumor formation, suggesting that PGI2 may play a role in chemoprevention.
We investigated several potential mechanisms for the down-regulation
of PGIS in human lung cancer. Using transcription reporter assays,
we show that single nucleotide polymorphisms in the PGIS promoter
can affect transcriptional activity. In addition, PGIS expression
in several human lung cancer cell lines is silenced by CpG methylation,
and we have mapped these sites across the variable number of tandem
repeats (VNTR) sequence in the promoter, as well as CpGs within exon
1 and the first intron. Finally, using fluorescence in situ hybridization,
we show that human lung cancer cell lines and lung cancer tissues
do not have a loss of the PGIS genomic region but multiple copies.
These results show that an individual's PGIS promoter haplotype can
play an important role in the predisposition for lung cancer and
CpG methylation provides an epigenetic mechanism for the down-regulated
PGIS expression. (Mol Cancer Res 2007;5(3):295-308)},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/5/3/295}
}
@ARTICLE{Stec2005,
author = {Stec, James and Wang, Jing and Coombes, Kevin and Ayers, Mark and
Hoersch, Sebastian and Gold, David L. and Ross, Jeffrey S and Hess,
Kenneth R. and Tirrell, Stephen and Linette, Gerald and Hortobagyi,
Gabriel N. and Symmans, W. Fraser and Pusztai, Lajos},
title = {Comparison of the Predictive Accuracy of DNA Array-Based Multigene
Classifiers across cDNA Arrays and Affymetrix GeneChips},
journal = {J. Mol. Diagn.},
year = {2005},
volume = {7},
pages = {357--367},
number = {3},
month = aug,
abstract = {We examined how well differentially expressed genes and multigene
outcome classifiers retain their class-discriminating values when
tested on data generated by different transcriptional profiling platforms.
RNA from 33 stage I-III breast cancers was hybridized to both Affymetrix
GeneChip and Millennium Pharmaceuticals cDNA arrays. Only 30% of
all corresponding gene expression measurements on the two platforms
had Pearson correlation coefficient r [≥] 0.7 when UniGene was
used to match probes. There was substantial variation in correlation
between different Affymetrix probe sets matched to the same cDNA
probe. When cDNA and Affymetrix probes were matched by basic local
alignment tool (BLAST) sequence identity, the correlation increased
substantially. We identified 182 genes in the Affymetrix and 45 in
the cDNA data (including 17 common genes) that accurately separated
91% of cases in supervised hierarchical clustering in each data set.
Cross-platform testing of these informative genes resulted in lower
clustering accuracy of 45 and 79%, respectively. Several sets of
accurate five-gene classifiers were developed on each platform using
linear discriminant analysis. The best 100 classifiers showed average
misclassification error rate of 2% on the original data that rose
to 19.5% when tested on data from the other platform. Random five-gene
classifiers showed misclassification error rate of 33%. We conclude
that multigene predictors optimized for one platform lose accuracy
when applied to data from another platform due to missing genes and
sequence differences in probes that result in differing measurements
for the same gene.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/7/3/357}
}
@ARTICLE{Stechova2012,
author = {Stechova, K. and Kolar, M. and Blatny, R. and Halbhuber, Z. and Vcelakova,
J. and Hubackova, M. and Petruzelkova, L. and Sumnik, Z. and Obermannova,
B. and Pithova, P. and Stavikova, V. and Krivjanska, M. and Neuwirth,
A. and Kolouskova, S. and Filipp, D.},
title = {Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit
Significant Differences in Basal Gene Expression Pattern of Immunocompetent
Cells Compared to Controls: Expression Pattern as Predeterminant
of Autoimmune Diabetes},
journal = {Scandinavian Journal of Immunology},
year = {2012},
volume = {75},
pages = {210--219},
number = {2},
abstract = {Expression features of genetic landscape which predispose an individual
to the type 1 diabetes are poorly understood. We addressed this question
by comparing gene expression profile of freshly isolated peripheral
blood mononuclear cells isolated from either patients with type 1
diabetes (T1D), or their first-degree relatives or healthy controls.
Our aim was to establish whether a distinct type of ‘prodiabetogenic’
gene expression pattern in the group of relatives of patients with
T1D could be identified. Whole-genome expression profile of nine
patients with T1D, their ten first-degree relatives and ten healthy
controls was analysed using the human high-density expression microarray
chip. Functional aspects of candidate genes were assessed using the
MetaCore software. The highest number of differentially expressed
genes (547) was found between the autoantibody-negative healthy relatives
and the healthy controls. Some of them represent genes critically
involved in the regulation of innate immune responses such as TLR
signalling and CCR3 signalling in eosinophiles, humoral immune reactions
such as BCR pathway, costimulation and cytokine responses mediated
by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway.
Our data demonstrate that expression profile of healthy relatives
of patients with T1D is clearly distinct from the pattern found in
the healthy controls. That especially concerns differential activation
status of genes and signalling pathways involved in proinflammatory
processes and those of innate immunity and humoral reactivity. Thus,
we posit that the study of the healthy relative’s gene expression
pattern is instrumental for the identification of novel markers associated
with the development of diabetes.},
doi = {10.1111/j.1365-3083.2011.02637.x},
issn = {1365-3083},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3083.2011.02637.x}
}
@ARTICLE{Stecyk2012,
author = {Jonathan A.W. Stecyk and Christine S. Couturier and Cathrine E. Fagernes
and Stian Ellefsen and Göran E. Nilsson},
title = {Quantification of heat shock protein mRNA expression in warm and
cold anoxic turtles (Trachemys scripta) using an external RNA control
for normalization},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2012},
volume = {7},
pages = {59 - 72},
number = {1},
abstract = {The mRNA expression of heat-shock protein 90 (HSP90) and heat-shock
cognate 70 (HSC70) was examined in cardiac chambers and telencephalon
of warm- (21 °C) and cold-acclimated (5 °C) turtles (Trachemys
scripta) exposed to normoxia, prolonged anoxia or anoxia followed
by reoxygenation. Additionally, the suitability of total RNA as well
as mRNA from β-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
and cyclophilin A (PPIA) for normalizing gene expression data was
assessed, as compared to the use of an external RNA control. Measurements
of HSP90 and HSC70 mRNA expression revealed that anoxia and reoxygenation
have tissue- and gene-specific effects. By and large, the alterations
support previous investigations on HSP protein abundance in the anoxic
turtle heart and brain, as well as the hypothesized roles of HSP90
and HSC70 during stress and non-stress conditions. However, more
prominent was a substantially increased HSP90 and HSC70 mRNA expression
in the cardiac chambers with cold acclimation. The finding provides
support for the notion that cold temperature induces a number of
adaptations in tissues of anoxia-tolerant vertebrates that precondition
them for winter anoxia. β-actin, GAPDH and PPIA mRNA expression
and total RNA also varied with oxygenation state and acclimation
temperature in a tissue- and gene-specific manner, as well as among
tissue types, thus disqualifying them as suitable for real-time RT-PCR
normalization. Thus, the present data highlights the advantages of
normalizing real-time RT-PCR data to an external RNA control, an
approach that also allows inter-tissue and potentially inter-species
comparisons of target gene expression.},
doi = {10.1016/j.cbd.2011.11.001},
issn = {1744-117X},
keywords = {Anoxia},
url = {http://www.sciencedirect.com/science/article/pii/S1744117X11000852}
}
@ARTICLE{Steele2011a,
author = {Steele, Michael A. and Croom, Jim and Kahler, Melissa and AlZahal,
Ousama and Hook, Sarah E. and Plaizier, Kees and McBride, Brian W.},
title = {Bovine rumen epithelium undergoes rapid structural adaptations during
grain-induced subacute ruminal acidosis},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {300},
pages = {R1515-1523},
number = {6},
abstract = {Alterations in rumen epithelial structure and function during grain-induced
subacute ruminal acidosis (SARA) are largely undescribed. In this
study, four mature nonlactating dairy cattle were transitioned from
a high-forage diet (HF; 0% grain) to a high-grain diet (HG; 65% grain).
After feeding the HG diet for 3 wk, the cattle were transitioned
back to the original HF diet, which was fed for an additional 3 wk.
Continuous ruminal pH was measured on a weekly basis, and rumen papillae
were biopsied during the baseline and at the first and final week
of each diet. The mean, minimum, and maximum daily ruminal pH were
depressed (P < 0.01) in the HG period compared with the HF period.
During the HG period, SARA was diagnosed only during week 1, indicating
ruminal adaptation to the HG diet. Microscopic examination of the
papillae revealed a reduction (P < 0.01) in the stratum basale, spinosum,
and granulosum layers, as well as total depth of the epithelium during
the HG period. The highest (P < 0.05) papillae lesion scores were
noted during week 1 when SARA occurred. Biopsied papillae exhibited
a decline in cellular junctions, extensive sloughing of the stratum
corneum, and the appearance of undifferentiated cells near the stratum
corneum. Differential mRNA expression of candidate genes, including
desmoglein 1 and IGF binding proteins 3, 5, and 6, was detected between
diets using qRT-PCR. These results suggest that the structural integrity
of the rumen epithelium is compromised during grain feeding and is
associated with the differential expression of genes involved in
epithelial growth and structure.},
doi = {10.1152/ajpregu.00120.2010},
eprint = {http://ajpregu.physiology.org/cgi/reprint/300/6/R1515.pdf},
url = {http://ajpregu.physiology.org/cgi/content/abstract/300/6/R1515}
}
@ARTICLE{Steele2011,
author = {Steele, Michael A. and Vandervoort, Gordon and AlZahal, Ousama and
Hook, Sarah E. and Matthews, James C. and McBride, Brian W.},
title = {Rumen epithelial adaptation to high-grain diets involves the coordinated
regulation of genes involved in cholesterol homeostasis},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {308--316},
number = {6},
month = mar,
abstract = {The molecular mechanisms underlying rumen epithelial adaption to high-grain
(HG) diets are unknown. To gain insight into the metabolic mechanisms
governing epithelial adaptation, mature nonlactating dairy cattle
(n = 4) were transitioned from a high-forage diet (HF, 0% grain)
to an HG diet (65% grain). After the cattle were fed the HG diet
for 3 wk, they returned to the original HF diet, which they were
fed for an additional 3 wk. Continuous ruminal pH, ruminal short
chain fatty acids, and plasma {beta}-hydroxybutyrate were measured
on a weekly basis, and rumen papillae were biopsied from the ventral
sac to assess alterations in mRNA expression profiles. The subacute
form of ruminal acidosis was diagnosed during the first week of the
HG period (4.6 {+/-} 1.6 h/day 1000 {micro}g/ml).
Many glomerular ultrastructural changes were seen in mutants, including
focal subendothelial delamination and widespread podocyte foot process
broadening, and glomerular basement membranes (GBMs) were significantly
thicker in 16-week-old mutants compared with controls. Moreover,
immunoelectron microscopy showed ectopic deposition of collagen {alpha}1{alpha}2{alpha}1(IV)
in GBM humps beneath podocytes. Significant increases in the number
of Ki-67-positive mesangial cells were also found, but glomerular
WT1 expression was significantly decreased, signifying podocyte death
and/or de-differentiation. Indeed, expression profiling of mutant
glomeruli suggested a negative regulatory feedback loop involving
the HIF{alpha} prolyl hydroxylase, Egln3. In addition, the brain
oxygen-binding protein, Neuroglobin, was induced in mutant podocytes.
We conclude that podocyte VHL is required for normal maintenance
of podocytes, GBM composition and ultrastructure, and glomerular
barrier properties.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/1/84}
}
@ARTICLE{Steenhard2009,
author = {Steenhard, Nina R. and Jungersen, Gregers and Kokotovic, Branko and
Beshah, Ethiopia and Dawson, Harry D. and Urban Jr., Joseph F. and
Roepstorff, Allan and Thamsborg, Stig M.},
title = {Ascaris suum infection negatively affects the response to a Mycoplasma
hyopneumoniae vaccination and subsequent challenge infection in pigs},
journal = {Vaccine},
year = {2009},
volume = {27},
pages = {5161--5169},
number = {37},
month = aug,
abstract = {Since their first introduction more than a century ago, vaccines have
become one of the most cost-effective tools to prevent and manage
infectious diseases in human and animal populations. It is vital
to understand the possible mechanisms that may impair optimal vaccine
efficacy. The hypothesis posed in this study was that a concurrent
Ascaris suum infection of pigs vaccinated with a Mycoplasma hyopneumoniae
(Mh) vaccine would modulate the protective immune response to a subsequent
challenge infection. Four groups of pigs were either (1) untreated
(group C), (2) vaccinated against Mh 3 weeks after the start of the
study (group V), (3) given a trickle infection with A. suum throughout
the study (group A), or (4) given a trickle infection with A. suum
and vaccinated against Mh (group AV). All pigs were subsequently
inoculated with live Mh bacteria 4 weeks after the Mh vaccination
and necropsied after another 4 weeks. All pigs in group V sero-converted
3 weeks after vaccination (100%), as opposed to only 33% of group
AV pigs that were Mh-vaccinated and given A. suum. At the end of
the study, only 78% of pigs in group AV had sero-converted. Pigs
in group AV had a higher mean percentage of lung pathology and the
variation was significantly higher in these pigs compared to pigs
in group V. The pattern of gene expression in the lungs and draining
lymph nodes indicated a local Th2-skewed response induced by A. suum.
Our study indicated that A. suum significantly compromised the effect
of Mh vaccination. The impact of reduced vaccine efficacy caused
by a common gastrointestinal helminth emphasises the importance of
parasite control. More focus should be put into this area of research
to outline the practical consequences of this interaction, and to
be able to predict, prevent and correct negative interactions.},
issn = {0264-410X},
keywords = {Ascaris suum, Mycoplasma hyopneumoniae, Vaccination, ELISA, Gene expression,
Lung pathology, Co-infection},
url = {http://www.sciencedirect.com/science/article/B6TD4-4WH6GG4-1/2/0fade7ce80a54e66eafb9601bd729087}
}
@ARTICLE{Steensma2007,
author = {Steensma, David P. and Hecksel, Kathleen A. and Porcher, Julie C.
and Lasho, Terra L.},
title = {Candidate gene mutation analysis in idiopathic acquired sideroblastic
anemia (refractory anemia with ringed sideroblasts)},
journal = {Leukemia Research},
year = {2007},
volume = {31},
pages = {623--628},
number = {5},
month = may,
abstract = {Background For most cases of idiopathic acquired sideroblastic anemia
(IASA), the molecular pathogenesis is unknown, despite the consistent
morphological signature of abundant pathological ringed sideroblasts
with their characteristic iron-engorged mitochondria. Moderately
elevated free erythrocyte protoporphyrin (FEP) levels have been described
in IASA, suggesting that the activity of ferrochelatase, the enzyme
that catalyzes the final step in heme biosynthesis (incorporation
of ferrous iron into protoporphyrin), might be diminished in erythroid
progenitor cells from IASA patients.Methods We confirmed FEP elevation
in IASA, then pursued a candidate gene approach that included screening
the gene encoding ferrochelatase, FECH, for promoter and coding region
mutations and mRNA expression changes in bone marrow from 37 patients
with IASA.Results The analytical techniques employed detected mutations
in a test cohort of previously undiagnosed patients with biochemical
evidence for erythropoietic protoporphyria, a condition resulting
from germline mutations in FECH, but somatic missense mutations of
FECH and its promoter were not observed in IASA patients. FECH was
modestly overexpressed in progenitor cells from patients with IASA,
compared with MDS patients without sideroblasts and healthy controls.
In addition, we analyzed ABCB7 and PUS1, genes implicated in congenital
sideroblastic anemia syndromes, but again found no coding mutations
in acquired cases.Conclusion We conclude that acquired mutations
in the factors currently known to cause inherited sideroblastic anemias
are uncommon in IASA.},
issn = {0145-2126},
keywords = {Sideroblastic anemia, Ferrochelatase, Erythropoietic protoporphyria,
Mutation analysis},
url = {http://www.sciencedirect.com/science/article/B6T98-4KGPPFX-1/2/c05c1d6bbe5ebcc0dc292e2ca7745673}
}
@ARTICLE{Steensma2009,
author = {Steensma, David P. and Neiger, Jessemy D. and Porcher, Julie C. and
Keats, J. Jonathan and Bergsagel, P. Leif and Dennis, Thomas R. and
Knudson, Ryan A. and Jenkins, Robert B. and Santana-Davila, Rafael
and Kumar, Rajiv and Ketterling, Rhett P.},
title = {Rearrangements and Amplification of IER3 (IEX-1) Represent a Novel
and Recurrent Molecular Abnormality in Myelodysplastic Syndromes},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {7518--7523},
number = {19},
month = oct,
abstract = {IER3 (formerly IEX-1) encodes a 27-kDa glycoprotein that regulates
death receptor-induced apoptosis, interacts with NF-{kappa}B pathways,
and increases expression rapidly in response to cellular stresses
such as irradiation. Animal models, gene expression microarray experiments,
and functional studies in cell lines have suggested a potential role
for IER3 in oncogenesis, but, to date, no abnormalities of IER3 at
the DNA level have been reported in patients with neoplasia. Here,
we describe breakpoint cloning of a t(6;9)(p21;q34) translocation
from a patient with a myelodysplastic syndrome (MDS), facilitated
by conversion technology and array-based comparative genomic hybridization,
which revealed a rearrangement translocating the IER3 coding region
away from critical flanking/regulatory elements and to a transcript-poor
chromosomal region, markedly decreasing expression. Using split-signal
and locus-specific fluorescence in situ hybridization (FISH) probes,
we analyzed 204 patients with diverse hematological malignancies
accompanied by clonal chromosome 6p21 abnormalities, and found 8
additional patients with MDS with IER3 rearrangements (translocations
or amplification). Although FISH studies on 157 additional samples
from patients with MDS and a normal-karyotype were unrevealing, and
sequencing the IER3 coding and proximal promoter regions of 74 MDS
patients disclosed no point mutations, reverse transcription-PCR
results suggested that dysregulated expression of IER3 is common
in MDS (61% >4-fold increase or decrease in expression with decreased
expression primarily in early MDS and increased expression primarily
in later MDS progressing toward leukemia), consistent with findings
in previous microarray experiments. These data support involvement
of IER3 in the pathobiology of MDS. [Cancer Res 2009;69(19):7518-23]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/19/7518}
}
@ARTICLE{Stefani2007,
author = {Stefani, Maurizio And Markus, M. Andrea And Lin, Ruby C. Y. And Pinese,
Mark And Dawes, Ian W. And Morris, Brian J.},
title = {The Effect of Resveratrol on a Cell Model of Human Aging},
journal = {Annals of the New York Academy of Sciences},
year = {2007},
volume = {1114},
pages = {407--418},
number = {1},
abstract = {Abstract: The natural polyphenol resveratrol stimulates sirtuins
and extends lifespan. Here resveratrol inhibited expression of replicative
senescence marker INK4a in human dermal fibroblasts, and 47 of 19,000
genes from microarray experiments were differentially expressed.
These included genes for growth, cell division, cell signaling, apoptosis,
and transcription. Genes involved in Ras and ubiquitin pathways,
Ras-GRF1, RAC3, and UBE2D3, were downregulated. The changes suggest
resveratrol might alter sirtuin-regulated downstream pathways, rather
than sirtuin activity. Serum deprivation and high confluency caused
nuclear translocation of the SIRT1-regulated transcription factor
FOXO3a. Our data indicate resveratrol's actions might cause FOXO
recruitment to the nucleus.},
issn = {1749-6632},
keywords = {resveratrol, nicotinamide, senescence, cell culture, microarray, fibroblasts},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1196/annals.1396.001}
}
@ARTICLE{Stefanic2010,
author = {Stefanic, Sasa and Spycher, Cornelia and Morf, Laura and Fabrias,
Gemma and Casas, Josefina and Schraner, Elisabeth and Wild, Peter
and Hehl, Adrian B. and Sonda, Sabrina},
title = {Glucosylceramide synthesis inhibition affects cell cycle progression,
membrane trafficking, and stage differentiation in Giardia lamblia},
journal = {J. Lipid Res.},
year = {2010},
volume = {51},
pages = {2527--2545},
number = {9},
month = sep,
abstract = {Synthesis of glucosylceramide via glucosylceramide synthase (GCS)
is a crucial event in higher eukaryotes, both for the production
of complex glycosphingolipids and for regulating cellular levels
of ceramide, a potent antiproliferative second messenger. In this
study, we explored the dependence of the early branching eukaryote
Giardia lamblia on GCS activity. Biochemical analyses revealed that
the parasite has a GCS located in endoplasmic reticulum (ER) membranes
that is active in proliferating and encysting trophozoites. Pharmacological
inhibition of GCS induced aberrant cell division, characterized by
arrest of cytokinesis, incomplete cleavage furrow formation, and
consequent block of replication. Importantly, we showed that increased
ceramide levels were responsible for the cytokinesis arrest. In addition,
GCS inhibition resulted in prominent ultrastructural abnormalities,
including accumulation of cytosolic vesicles, enlarged lysosomes,
and clathrin disorganization. Moreover, anterograde trafficking of
the encystations-specific protein CWP1 was severely compromised and
resulted in inhibition of stage differentiation. Our results reveal
novel aspects of lipid metabolism in G. lamblia and specifically
highlight the vital role of GCS in regulating cell cycle progression,
membrane trafficking events, and stage differentiation in this parasite.
In addition, we identified ceramide as a potent bioactive molecule,
underscoring the universal conservation of ceramide signaling in
eukaryotes.},
url = {http://www.jlr.org/cgi/content/abstract/51/9/2527}
}
@ARTICLE{Stefanovic2008,
author = {Stefanovic, Dragana and Kusic, Jelena and Divac, Aleksandra and Tomic,
Branko},
title = {Formation of Noncanonical DNA Structures Mediated by Human ORC4,
a Protein Component of the Origin Recognition Complex†},
journal = {Biochemistry},
year = {2008},
volume = {47},
pages = {8760-8767},
number = {33},
note = {PMID: 18652488},
doi = {10.1021/bi800684f},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi800684f},
url = {http://pubs.acs.org/doi/abs/10.1021/bi800684f}
}
@ARTICLE{Stegall2002,
author = {Stegall, Mark and Park, Walter and Kim, Dean and Kremers, Walter},
title = {Gene Expression During Acute Allograft Rejection: Novel Statistical
Analysis of Microarray Data},
journal = {American Journal of Transplantation},
year = {2002},
volume = {2},
pages = {913--925},
number = {10},
abstract = {High-throughput microarrays promise a comprehensive analysis of complex
biological processes, yet their applicability is hampered by problems
of reproducibility and data management. The current study examines
some of the major questions of microarray use in a well-described
model of allograft rejection. Using the Brown Norway to Lewis heterotopic
heart transplant model, highly purified RNA was isolated from cardiac
tissue at postoperative days (POD) 3, 5 and 7 and hybridized onto
Affymetrix U34A microarrays. Using the log average ratio (LAR), changes
in gene expression were monitored at each timepoint and p-values
generated through statistical analysis. Microarray data were verified
for 13 significant transcripts using RT-PCR. Of the 8800 transcripts
studied, 2864 were increased on POD 3, 1418 on POD 5 and 2745 on
POD 7. Verifying previous studies, many up-regulated genes appeared
to be associated with the inflammatory process and graft infiltrating
cells. Down-regulated transcripts included many novel molecules such
as SC1 and decorin. LAR analysis provides a useful approach to analyze
microarray data. Results were reproducible and correlated well with
both RT-PCR and prior studies. Most importantly, these results provide
new insights into the pathogenesis of acute rejection and suggest
new molecules for future studies.},
issn = {1600-6143},
keywords = {Bioinformatics, cardiac transplantation, gene expression, immune response,
microarray},
publisher = {Munksgaard International Publishers},
url = {http://dx.doi.org/10.1034/j.1600-6143.2002.21007.x}
}
@ARTICLE{Stegk2009,
author = {Stegk, J.P. and Ebert, B. and Martin, H.-J. and Maser, E.},
title = {Expression profiles of human 11[beta]-hydroxysteroid dehydrogenases
type 1 and type 2 in inflammatory bowel diseases},
journal = {Molecular and Cellular Endocrinology},
year = {2009},
volume = {301},
pages = {104--108},
number = {1-2},
month = mar,
abstract = {Inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative
colitis (UC) are characterized by an increase in pro-inflammatory
cytokines. On the other hand, endogenous cortisol is regarded as
physiological compound to combat inflammation. The local activation
of glucocorticoids is mediated by 11[beta]-hydroxysteroid dehydrogenase
type 1 (11[beta]-HSD1) which increases cortisol, and 11[beta]-HSD2
which decreases cortisol concentrations. We hypothesized that in
inflamed tissues of patients suffering from inflammatory bowel diseases
11[beta]-HSD1 is upregulated whereas 11[beta]-HSD2 is downregulated.
By using quantitative real-time PCR, we investigated the transcription
levels of 11[beta]-HSD1 and 11[beta]-HSD2 in patients diagnosed with
CD or UC. Expression of 11[beta]-HSD1 was significantly elevated
in inflamed tissue compared to non-inflamed colonic tissue in both,
CD (2.7-fold) and UC (3.8-fold), whereas 11[beta]-HSD2 expression
was decreased in the same samples. In both diseases, male patients
showed a more pronounced upregulation of 11[beta]-HSD1 (CD: 4.8-fold,
UC: 6.5-fold) compared to females (CD: 1.8-fold, UC: 1.8-fold), a
fact which might be due to the higher levels of circulating anti-inflammatory
estrogens in women. Our data support the hypothesis that both enzymes
play a crucial role in inflammation by affecting local tissue ratios
between active and inactive glucocorticoids.},
booktitle = {Pre-receptor steroid metabolism as target for pharmacological treatment},
issn = {0303-7207},
keywords = {11[beta]-Hydroxysteroid dehydrogenase, Inflammation, Inflammatory
bowel disease, Crohn's disease, Ulcerative colitis, Cortisol},
url = {http://www.sciencedirect.com/science/article/B6T3G-4TTHWH0-4/2/a86d7ab0f76bbd37402d24d2c8569bc4}
}
@ARTICLE{Stehle2010,
author = {Stehle, Melanie E. and Hanczaruk, Matthias and Schwarz, Susanne C.
N. and Göbel, Thomas W. and Mueller, Ralf S.},
title = {Effects of polyunsaturated fatty acids on isolated canine peripheral
blood mononuclear cells and cytokine expression (IL-4, IFN-γ, TGF-β)
in healthy and atopic dogs},
journal = {Veterinary Dermatology},
year = {2010},
volume = {21},
pages = {113--118},
number = {1},
abstract = {Abstract Polyunsaturated fatty acids (PUFA) have been used to treat
dogs with atopic dermatitis but the mechanism of action has not been
well understood. The aim of this study was to evaluate the in vitro
influence of PUFA on canine peripheral blood mononuclear cells (PBMC).
PBMC isolated from eleven dogs with atopic dermatitis and eleven
healthy control dogs were stimulated with concanavalin A and Dermatophagoides
farinae extract in the presence of linoleic acid (LA), γ-linolenic
acid (GLA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA)/docosahexaenoic
acid (DHA) and GLA/EPA/DHA. Subsequently, quantitative polymerase
chain reaction (qPCR) for interferon (IFN)-γ, interleukin (IL)-4
and transforming growth factor (TGF)-β m-RNA was performed. In the
presence of concanavalin A, only PBMC of healthy dogs showed a gradual
reduction in proliferation index from incubation without PUFA to
incubation with ALA, EPA/DHA and GLA/EPA/DHA, respectively. A similar
reduction was seen in normal and in atopic dogs in the presence of
D. farinae allergen after incubation with ALA, EPA/DHA and GLA/EPA/DHA.
In both groups IL-4 and IFN-γ but not TGF-β gene transcription
was upregulated, when cells were incubated with D. farinae. Allergen-induced
upregulation was not influenced by incubation with PUFA. These findings
suggest that PUFA are able to influence proliferation of peripheral
blood mononuclear cells in healthy and atopic dogs but do not seem
to influence gene transcription of IL-4, IFN-γ and TGF-β.
Résumé Les acides gras polyinsaturés (PUFA) ont été utilisés
pour traiter les chiens atteints de dermatite atopique mais leur
mécanisme d’action reste mal compris. L’objectif de cette étude
était d’évaluer l’influence in vitro des PUFA sur les cellules
mononucléées (PBMC) du sang périphérique canin. Les PBMC isolées
de onze chiens atopiques et onze chiens sains contrôles ont été
stimulés avec la concanavalin A et un extrait de Dermatophagoides
farinae en présence d’acide linoleique (LA), d’acide γ-linolenique
(GLA), d’acide α-linolenique (ALA), d’acide eicosapentaenoique
(EPA)/acide docosahexaenoique (DHA) and GLA/EPA/DHA. Par la suite,
une PCR quantitative (Polymerase Chain Reaction) a été réalisée
pour l’interféron (IFN)-γ, interleukin (IL)-4, et le transforming
growth factor (TGF)-β m-RNA. En présence de concanavalin A, seuls
les PBMC des chiens sains ont montrés une diminution graduelle de
l’index de prolifération depuis l’incubation sans PUFA à l’incubation
avec ALA, EPA/DHA et GLA/EPA/DHA respectivement. Une réduction similaire
a été observée chez les chiens normaux et atopiques en présence
de l’allergène D. farinae après incubation avec ALA, EPA/DHA
and GLA/EPA/DHA. Dans les deux groupes IL-4 et IFN-γ mais pas dans
le groupe TGF- β, la transcription a été régulée à la hausse
lorsque les cellules étaient incubées avec D. farinae. Cette régulation
induite par l’allergène n’a pas été influencée par l’incubation
avec les PUFA. Ces résultats suggèrent que les PUFA peuvent influencer
la prolifération des cellules mononucléées du sang périphérique
chez les chiens sains et les chiens atopiques mais ne semblent pas
influencer la transcription des gènes de IL-4, IFN-γ et TGF-β.
Resumen Los ácidos grasos poliinsaturados (PUFA) han sido utilizados
en el tratamiento de perros con dermatitis atópica, pero el mecanismo
de acción no ha sido bien elucidado. El propósito de este estudio
fue evaluar la influencia in vitro de PUFA en células mononucleares
caninas de sangre periférica (PBMC). PBMC se aislaron de once perros
con dermatitis atópica y de once perros sanos como control. Estos
se estimularon con concanavalina A y extracto de Dermatophagoides
faringe en presencia de acido linoleico (LA), acido γ-linoleico
(GLA), acido α-linoelico (ALA), ácido eicosapentanoico (EPA)/ácido
docosahexanoico (DHA) y GLA/EPA/DHA. Posteriormente se realizó una
reacción de polimerasa en cadena cuantitativa para el RNA mensajero
de IFN- γ, IL-4 y factor transformador de crecimiento (TGF-β).
En presencia de concanavalina A, sólo los PBMC de perros sanos mostraron
una reducción gradual del Ãndice proliferativo de la incubación
sin PUFA a la incubación con ALA, EPA/DHA y GLA/EPA/DHA, respectivamente.
Una reducción similar se observo en perros normales y atópicos
en presencia del extracto de D. farinae tras la incubacion con ALA,
EPA/DHA y GLA/EPA/DHA. En ambos grupos la transcripción de los genes
de IL-4 e IFN- γ, pero no TGF- β estaba aumentada cuando las células
se incubaron con D. farinae. La elevación de la transcripción inducida
por el alergeno no estuvo afectada por la incubación con PUFA. Estos
hallazgos indican que PUFA son capaces de afectar la proliferación
de celulas mononucleares de sangre periférica en perros sanos y
atópicos pero no parece afectar las transcripcion de los genes de
IL-4, IFN- γ y TGF- β.
Zusammenfassung Mehrfach-ungesättigte Fettsäuren (PUFA) werden verwendet,
um Hunde mit atopischer Dermatitis zu behandeln, wobei aber der Aktionsmechanismus
nicht sehr gut verstanden wird. Das Ziel dieser Studie war es, den
in vitro Einfluss von PUFA auf canine periphere mononukleäre Blutzellen
(PBMC) zu evaluieren. PBMC, die von elf Hunden mit atopischer Dermatitis
und von elf gesunden Hunden als Kontrollen isoliert worden waren,
wurden mit Concanavalin A und Dermatophagoides farinae Extrakt im
Beisein von Linolsäure (LA), γ-Linolsäure (GLA), α-Linolsäure
(ALA), Eicosapentaensäure (EPA)/Docosahexaensäure (DHA) und GLA/EPA/DHA
stimuliert. In der Folge wurde eine quantitative Polymerasekettenreaktion
(qPCR) für Interferon (IFN)-γ, Interleukin (IL)-4 und Transforming
Growth Faktor(TGF)-β mRNA durchgeführt. Mit Concanavalin A zeigten
nur die PBMC der gesunden Hunde von der Inkubation ohne PUFA bis
zur Inkubation mit ALA bzw. EPA/DHA bzw. GLA/EPA/DHA. eine graduelle
Reduktion des Proliferationsindex. Eine ähnliche Reduktion wurde
bei normalen und atopischen Hunden im Beisein von D. farinae Allergen
nach der Inkubation mit ALA, EPA/DHA und GLA/EPA/DHA gefunden. In
beiden Gruppen war die IL-4 und die IFN-γ, aber nicht die TGF-β
Gen Transkription erhöht, wenn die Zellen mit D. farinae inkubiert
wurden. Die Allergen-induzierte Erhöhung wurde von einer Inkubation
mit PUFA nicht beeinflusst. Diese Ergebnisse weisen darauf hin, dass
PUFA die Proliferation der peripheren mononukleären Blutzellen bei
gesunden und atopischen Hunden beeinflussen können, dass sie aber
die Gen Transkription von IL-4, IFN-γ und TGF-β scheinbar nicht
beeinflussen.},
issn = {1365-3164},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3164.2009.00860.x}
}
@ARTICLE{Steibel2009,
author = {Steibel, J. P. and Wysocki, M. and Lunney, J. K. and Ramos, A. M.
and Hu, Z.-L. and Rothschild, M. F. and Ernst, C. W.},
title = {Assessment of the swine protein-annotated oligonucleotide microarray},
journal = {Animal Genetics},
year = {2009},
volume = {40},
pages = {883--893},
number = {6},
abstract = {Summary The specificity and utility of the swine protein-annotated
oligonucleotide microarray, or Pigoligoarray (http://www.pigoligoarray.org),
has been evaluated by profiling the expression of transcripts from
four porcine tissues. Tools for comparative analyses of expression
on the Pigoligoarray were developed including HGNC identities and
comparative mapping alignments with human orthologs. Hybridization
results based on the Pigoligoarray’s sets of control, perfect match
(PM) and deliberate mismatch (MM) probes provide an important means
of assessing non-specific hybridization. Simple descriptive diagnostic
analyses of PM/MM probe sets are introduced in this paper as useful
tools for detecting non-specific hybridization. Samples of RNA from
liver, brain stem, longissimus dorsi muscle and uterine endothelium
from four pigs were prepared and hybridized to the arrays. Of the
total 20Â 400 oligonucleotides on the Pigoligoarray, 12Â 429 transcripts
were putatively differentially expressed (DE). Analyses for tissue-specific
expression [over-expressed in one tissue with respect to all the
remaining three tissues (q < 0.01)] identified 958 DE transcripts
in liver, 726 in muscle, 286 in uterine endothelium and 1027 in brain
stem. These hybridization results were confirmed by quantitative
PCR (QPCR) expression patterns for a subset of genes after affirming
that cDNA and amplified antisense RNA (aRNA) exhibited similar QPCR
results. Comparison to human ortholog expression confirmed the value
of this array for experiments of both agricultural importance and
for tests using pigs as a biomedical model for human disease.},
issn = {1365-2052},
keywords = {amplified antisense RNA, long oligo array, pig, quantitative PCR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2009.01928.x}
}
@ARTICLE{Steig2011,
author = {Steig, Amy J. and Jackman, Matthew R. and Giles, Erin D. and Higgins,
Janine A. and Johnson, Ginger C. and Mahan, Chad and Melanson, Edward
L. and Wyatt, Holly R. and Eckel, Robert H. and Hill, James O. and
MacLean, Paul S.},
title = {Exercise reduces appetite and traffics excess nutrients away from
energetically efficient pathways of lipid deposition during the early
stages of weight regain},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {301},
pages = {R656-667},
number = {3},
abstract = {The impact of regular exercise on energy balance, fuel utilization,
and nutrient availability, during weight regain was studied in obese
rats, which had lost 17% of their weight by a calorie-restricted,
low-fat diet. Weight reduced rats were maintained for 6 wk with and
without regular treadmill exercise (1 h/day, 6 days/wk, 15 m/min).
In vivo tracers and indirect calorimetry were then used in combination
to examine nutrient metabolism during weight maintenance (in energy
balance) and during the first day of relapse when allowed to eat
ad libitum (relapse). An additional group of relapsing, sedentary
rats were provided just enough calories to create the same positive
energy imbalance as the relapsing, exercised rats. Exercise attenuated
the energy imbalance by 50%, reducing appetite and increasing energy
requirements. Expenditure increased beyond the energetic cost of
the exercise bout, as exercised rats expended more energy to store
the same nutrient excess in sedentary rats with the matched energy
imbalance. Compared with sedentary rats with the same energy imbalance,
exercised rats exhibited the trafficking of dietary fat toward oxidation
and away from storage in adipose tissue, as well as a higher net
retention of fuel via de novo lipogenesis in adipose tissue. These
metabolic changes in relapse were preceded by an increase in the
skeletal muscle expression of genes involved in lipid uptake, mobilization,
and oxidation. Our observations reveal a favorable shift in fuel
utilization with regular exercise that increases the energetic cost
of storing excess nutrients during relapse and alterations in circulating
nutrients that may affect appetite. The attenuation of the biological
drive to regain weight, involving both central and peripheral aspects
of energy homeostasis, may explain, in part, the utility of regular
exercise in preventing weight regain after weight loss.},
doi = {10.1152/ajpregu.00212.2011},
eprint = {http://ajpregu.physiology.org/cgi/reprint/301/3/R656.pdf},
url = {http://ajpregu.physiology.org/cgi/content/abstract/301/3/R656}
}
@ARTICLE{Steil2003,
author = {Steil, Leif and Hoffmann, Tamara and Budde, Ina and Volker, Uwe and
Bremer, Erhard},
title = {Genome-Wide Transcriptional Profiling Analysis of Adaptation of Bacillus
subtilis to High Salinity},
journal = {J. Bacteriol.},
year = {2003},
volume = {185},
pages = {6358--6370},
number = {21},
month = nov,
abstract = {The gram-positive soil bacterium Bacillus subtilis often faces increases
in the salinity in its natural habitats. A transcriptional profiling
approach was utilized to investigate both the initial reaction to
a sudden increase in salinity elicited by the addition of 0.4 M NaCl
and the cellular adaptation reactions to prolonged growth at high
salinity (1.2 M NaCl). Following salt shock, a sigB mutant displayed
immediate and transient induction and repression of 75 and 51 genes,
respectively. Continuous propagation of this strain in the presence
of 1.2 M NaCl triggered the induction of 123 genes and led to the
repression of 101 genes. In summary, our studies revealed (i) an
immediate and transient induction of the SigW regulon following salt
shock, (ii) a role of the DegS/DegU two-component system in sensing
high salinity, (iii) a high-salinity-mediated iron limitation, and
(iv) a repression of chemotaxis and motility genes by high salinity,
causing severe impairment of the swarming capability of B. subtilis
cells. Initial adaptation to salt shock and continuous growth at
high salinity share only a limited set of induced and repressed genes.
This finding strongly suggests that these two phases of adaptation
require distinctively different physiological adaptation reactions
by the B. subtilis cell. The large portion of genes with unassigned
functions among the high-salinity-induced or -repressed genes demonstrates
that major aspects of the cellular adaptation of B. subtilis to high
salinity are unexplored so far.},
url = {http://jb.asm.org/cgi/content/abstract/185/21/6358}
}
@ARTICLE{Steilmann2010,
author = {Steilmann, Cornelia and Cavalcanti, Marcia C O and Bartkuhn, Marek
and Pons-Kuhnemann, Jorn and Schuppe, Hans-Christian and Weidner,
Wolfgang and Steger, Klaus and Paradowska, Agnieszka},
title = {The interaction of modified histones with the bromodomain testis-specific
(BRDT) gene and its mRNA level in sperm of fertile donors and subfertile
men},
journal = {Reproduction},
year = {2010},
volume = {140},
pages = {435--443},
number = {3},
month = sep,
abstract = {As histone modifications have been suggested to be involved in the
regulation of gene expression after fertilisation, the present study
aimed to analyze the interaction between the bromodomain testis-specific
(BRDT) gene and differentially modified histones in human spermatozoa.
The BRDT transcript level was studied to identify possible correlations
between epigenetic changes, mRNA level and subfertility associated
with impaired sperm chromatin condensation. Chromatin immunoprecipitation
(ChIP) was performed with ejaculates from fertile and subfertile
men using antibodies against specifically acetylated and methylated
histone H3. Immunoprecipitated DNA was analysed by real-time quantitative
PCR with primer pairs for BRDT. The BRDT mRNA level was screened
by real-time RT-PCR. ChIP assay revealed co-localisation of acetylated
and methylated histones within promoter and exon regions of the BRDT
gene in fertile men. Interestingly, reduced binding of investigated
modified histone modifications was observed in the BRDT promoter
of subfertile patients. Different mRNA levels of BRDT have been detected
in a group of infertile patients, as well as in fertile men. Enrichment
of methylated histones within the BRDT promoter of fertile sperm
suggests that this epigenetic mark may cause repression of BRDT after
fertilisation, and may be changed in infertile patients. Our data
suggest that reduced histone methylation in the promoter of BRDT
may be associated with increased transcript levels in subfertile
patients.},
url = {http://www.reproduction-online.org/cgi/content/abstract/140/3/435}
}
@ARTICLE{Stein2011,
author = {Katrin Stein and Anke Borowicki and Daniel Scharlau and Anika Schettler
and Kerstin Scheu and Ursula Obst and Michael Glei},
title = {Effects of synbiotic fermentation products on primary chemoprevention
in human colon cells},
journal = {The Journal of Nutritional Biochemistry},
year = {2011},
pages = { - },
number = {0},
abstract = {The consumption of synbiotics, a mixture of probiotics and indigestible
food constituents such as dietary fiber, has been reported to reduce
colon cancer risk. We investigated the effects of fermented wheat
aleurone enriched with the probiotics Lactobacillus rhamnosus GG/Bifidobacterium
animalis supsp. lactis on the gene expression and functional end
points related to cellular defence in HT29 and primary human colon
cells. Aleurone was digested and fermented in vitro with/without
probiotics. The resulting fermentation supernatants (fs) were analyzed
for concentrations of deoxycholic acid and ammonia. The cells were
treated with the fs, and effects on gene expression of catalase,
GSTP1 and SULT2B1, enzyme activity of catalase and glutathione S-transferase
as well as H2O2-induced DNA damage were examined. Fermentation of
aleurone reduced deoxycholic acid concentration by 84%, while the
probiotics enhanced this effect. Ammonia was increased by fs aleurone,
whereas a reduction occurred by the addition of L. rhamnosus GG/B.
animalis supsp. lactis 12. GSTP1 expression tended to result in an
increase by the fs aleurone in both cell types, whereas the probiotics
could not additionally increase the effect. Catalase was not modulated
by fs aleurone enriched with probiotics. Only in HT29 cells, expression
of SULT2B1 was enhanced by fs aleurone. Enzyme activity of catalase
and glutathione S-transferase was induced (2–3.6 fold, 72 h) in
HT29 cells only. Addition of probiotics had no influence on this
effect. In HT29 cells, a reduced H2O2-induced DNA damage by the fs
aleurone after 48 h, enhanced by the addition of probiotics, was
detected. The observed effects could improve detoxification of xenobiotics
and therefore may lower colon cancer risk.},
doi = {10.1016/j.jnutbio.2011.03.022},
issn = {0955-2863},
keywords = {Wheat aleurone},
url = {http://www.sciencedirect.com/science/article/pii/S0955286311001276}
}
@ARTICLE{Stein2012,
author = {Stein, Ricardo J. and Waters, Brian M.},
title = {Use of natural variation reveals core genes in the transcriptome
of iron-deficient Arabidopsis thaliana roots},
journal = {J. Exp. Bot.},
year = {2012},
volume = {63},
pages = {1039-1055},
number = {2},
abstract = {Iron (Fe) is an essential mineral micronutrient for plants and animals.
Plants respond to Fe deficiency by increasing root uptake capacity.
Identification of gene networks for Fe uptake and homeostasis could
result in improved crop growth and nutritional value. Previous studies
have used microarrays to identify a large number of genes regulated
by Fe deficiency in roots of three Arabidopsis ecotypes. However,
a large proportion of these genes may be involved in secondary or
genotype-influenced responses rather than in a universal role in
Fe uptake or homeostasis. Here we show that a small percentage of
the Fe deficiency transcriptome of two contrasting ecotypes, Kas-1
and Tsu-1, was shared with other ecotypes. Kas-1 and Tsu-1 had different
timing and magnitude of ferric reductase activity upon Fe withdrawal,
and different categories of overrepresented Fe-regulated genes. To
gain insights into universal responses of Arabidopsis to Fe deficiency,
the Kas-1 and Tsu-1 transcriptomes were compared with those of Col-0,
Ler, and C24. In early Fe deficiency (24-48 h), no Fe-downregulated
genes and only 10 upregulated genes were found in all ecotypes, and
only 20 Fe-downregulated and 58 upregulated genes were found in at
least three of the five ecotypes. Supernode gene networks were constructed
to visualize conserved Fe homeostasis responses. Contrasting gene
expression highlighted different responses to Fe deficiency between
ecotypes. This study demonstrates the use of natural variation to
identify central Fe-deficiency-regulated genes in plants, and identified
genes with potential new roles in signalling during Fe deficiency.},
doi = {10.1093/jxb/err343},
eprint = {http://jxb.oxfordjournals.org/cgi/reprint/63/2/1039.pdf},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/63/2/1039}
}
@ARTICLE{Stein2006,
author = {Stein, Ulrike and Arlt, Franziska and Walther, Wolfgang and Smith,
Janice and Waldman, Todd and Harris, Erik D. and Mertins, Susan D.
and Heizmann, Claus W. and Allard, David and Birchmeier, Walter and
Schlag, Peter M. and Shoemaker, Robert H.},
title = {The Metastasis-Associated Gene S100A4 Is a Novel Target of [beta]-catenin/T-cell
Factor Signaling in Colon Cancer},
journal = {Gastroenterology},
year = {2006},
volume = {131},
pages = {1486--1500},
number = {5},
month = nov,
abstract = {Background & Aims: Activation of the Wnt/[beta]-catenin pathway is
frequently observed in colorectal cancers. Our aim was to elucidate
the impact of gain-of-function [beta]-catenin on the metastasis-associated
gene S100A4 in human colon cancer cell lines and tumors. Methods:
We analyzed cell lines heterozygous for gain-of-function and wild-type
[beta]-catenin, and variants homozygous for gain- or loss-of-function
mutation in [beta]-catenin, for S100A4 expression, cell motility,
and in vivo metastasis. [beta]-catenin-mediated S100A4 promoter activation
was tested by reporter assays. For human colon carcinomas, S100A4
expression, [beta]-catenin genotype, and metachronous metastasis
were correlated. Results: We identified S100A4 as the most regulated
gene by gain-of-function [beta]-catenin using a 10K microarray. Cell
lines with gain-of-function [beta]-catenin expressed up to 60-fold
elevated S100A4 levels, displayed strongly increased migration and
invasion in vitro, and induced metastasis in mice. S100A4 small interfering
RNA, [beta]-catenin small interfering RNA, or dominant negative T-cell
factor (TCF) knocked down S100A4 and blocked biological effects.
S100A4 complementary DNA transfection increased migration and invasion.
We identified a TCF binding site within the S100A4 promoter and demonstrated
the direct binding of heterodimeric [beta]-catenin/TCF complexes.
Reporter assays confirmed the [beta]-catenin-induced S100A4 promoter
activity. Furthermore, S100A4 mRNA expression was increased in primary
colon cancers, which later developed distant metastases, compared
to non-metastasizing tumors. Colon tumors heterozygous for gain-of-function
[beta]-catenin showed concomitant nuclear [beta]-catenin localization,
high S100A4 expression, and metastases. Conclusions: S100A4 is a
direct [beta]-catenin/TCF target, induces migration and invasion
in vitro and metastasis in vivo, and has value for prognosis of metastasis
formation in colon cancer patients.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4KPN45R-4/2/fcb223f585e914f36fb37353991902ae}
}
@ARTICLE{Stein2011a,
author = {Stein, Ulrike and Burock, Susen and Herrmann, Pia and Wendler, Ina
and Niederstrasser, Markus and Wernecke, Klaus-Dieter and Schlag,
Peter M.},
title = {Diagnostic and Prognostic Value of Metastasis Inducer S100A4 Transcripts
in Plasma of Colon, Rectal, and Gastric Cancer Patients},
journal = {The Journal of Molecular Diagnostics},
year = {2011},
volume = {13},
pages = {189--198},
number = {2},
month = mar,
abstract = {Early detection of tumors and metastases is critical for improving
treatment strategies and patient outcomes. The development of molecular
markers and simple tests that are clinically applicable for detection,
prognostication, and therapy monitoring is strongly needed. The gene
S100A4 has long been known to act as a metastasis inducer. High S100A4
levels in the primary tumor are prognostic for metachronous metastasis
and correlate with reduced patient survival. We provide, for the
first time, a plasma-based assay for transcript quantification of
S100A4 in gastrointestinal patients' plasma. We conducted a study
to define the diagnostic and prognostic power of S100A4 transcripts
using 466 plasma samples from colon, rectal, and gastric cancer patients.
Plasma was separated, RNA was isolated, and S100A4 mRNA was determined
by quantitative RT-PCR. S100A4 transcripts were increased in cancer
patients of each entity (P < 0.0001) and all disease stages (P <
0.05), compared with tumor-free volunteers (sensitivities of 96%,
74%, and 90% and specificities of 59%, 82%, and 71%, for colon, rectal,
and gastric cancer patients, respectively). Prospectively analyzed
follow-up patients who later experienced metastasis showed higher
S100A4 levels than follow-up patients without metastasis. Disease-free
survival was decreased in high S100A4-expressing follow-up colorectal
cancer patients (P = 0.013). In summary, we developed a method for
quantitative S100A4 transcript determination in plasma that allows
clinical application routinely. We demonstrated the diagnostic and
prognostic potential of this method for early defining cancer staging
and patients' risk for metastasis.},
issn = {1525-1578},
url = {http://www.sciencedirect.com/science/article/pii/S1525157810000577}
}
@ARTICLE{Steiner2009,
author = {Steiner, Alexandre A. and Hunter, John C. and Phipps, Sean M. and
Nucci, Tatiane B. and Oliveira, Daniela L. and Roberts, Jennifer
L. and Scheck, Adrienne C. and Simmons, Daniel L. and Romanovsky,
Andrej A.},
title = {Cyclooxygenase-1 or -2--which one mediates lipopolysaccharide-induced
hypothermia?},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2009},
volume = {297},
pages = {R485--494},
number = {2},
month = aug,
abstract = {Systemic inflammation is associated with either fever or hypothermia.
Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase
(COX)-2 and not by COX-1. However, it is still disputed whether COX-2,
COX-1, neither, or both mediate(s) responses to severe systemic inflammation,
and, in particular, the hypothermic response. We compared the effects
of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep
body temperature (Tb) of rats injected with a lower (10 {micro}g/kg
iv) or higher (1,000 {micro}g/kg iv) dose of LPS at different ambient
temperatures (Tas). At a neutral Ta (30{degrees}C), the rats responded
to LPS with a polyphasic fever (lower dose) or a brief hypothermia
followed by fever (higher dose). SC-236 (2.5 mg/kg iv) blocked the
fever induced by either LPS dose, whereas SC-560 (5 mg/kg iv) altered
neither the febrile response to the lower LPS dose nor the fever
component of the response to the higher dose. However, SC-560 blocked
the initial hypothermia caused by the higher LPS dose. At a subneutral
Ta (22{degrees}C), the rats responded to LPS with early (70-90 min,
nadir) dose-dependent hypothermia. The hypothermic response to either
dose was enhanced by SC-236 but blocked by SC-560. The hypothermic
response to the higher LPS dose was associated with a fall in arterial
blood pressure. This hypotensive response was attenuated by either
SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension,
the functional activity of the COX-1 pathway (COX-1-mediated PGE2
synthesis ex vivo) increased in the spleen but not liver, lung, kidney,
or brain. The expression of splenic COX-1 was unaffected by LPS.
We conclude that COX-1, but not COX-2, mediates LPS hypothermia,
and that both COX isoforms are required for LPS hypotension.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/297/2/R485}
}
@ARTICLE{Steiner2011a,
author = {Steiner, Elisabeth and Dago, Angel E. and Young, Danielle I. and
Heap, John T. and Minton, Nigel P. and Hoch, James A. and Young,
Michael},
title = {Multiple orphan histidine kinases interact directly with Spo0A to
control the initiation of endospore formation in Clostridium acetobutylicum},
journal = {Molecular Microbiology},
year = {2011},
volume = {80},
pages = {641--654},
number = {3},
abstract = {Summary The phosphorylated Spo0A transcription factor controls the
initiation of endospore formation in Clostridium acetobutylicum,
but genes encoding key phosphorelay components, Spo0F and Spo0B,
are missing in the genome. We hypothesized that the five orphan histidine
kinases of C. acetobutylicum interact directly with Spo0A to control
its phosphorylation state. Sequential targeted gene disruption and
gene expression profiling provided evidence for two pathways for
Spo0A activation, one dependent on a histidine kinase encoded by
cac0323, the other on both histidine kinases encoded by cac0903 and
cac3319. Purified Cac0903 and Cac3319 kinases autophosphorylated
and transferred phosphoryl groups to Spo0A in vitro, confirming their
role in Spo0A activation in vivo. A cac0437 mutant hyper-sporulated,
suggesting that Cac0437 is a modulator that prevents sporulation
and maintains cellular Spo0A∼P homeostasis during growth. Accordingly,
Cac0437 has apparently lost the ability to autophosphorylate in vitro;
instead it catalyses the ATP-dependent dephosphorylation of Spo0A∼P
releasing inorganic phosphate. Direct phosphorylation of Spo0A by
histidine kinases and dephosphorylation by kinase-like proteins may
be a common feature of the clostridia that may represent the ancestral
state before the great oxygen event some 2.4 billion years ago, after
which additional phosphorelay proteins were recruited in the evolutionary
lineage that led to the bacilli.},
doi = {10.1111/j.1365-2958.2011.07608.x},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2011.07608.x}
}
@ARTICLE{Steiner2011,
author = {Steiner, Laurie A. and Schulz, Vincent P. and Maksimova, Yelena and
Wong, Clara and Gallagher, Patrick G.},
title = {Patterns of Histone H3 Lysine 27 Monomethylation and Erythroid Cell
Type-specific Gene Expression},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {39457-39465},
number = {45},
abstract = {Post-translational histone modifications, acting alone or in a context-dependent
manner, influence numerous cellular processes via their regulation
of gene expression. Monomethylation of histone H3 lysine 27 (K27me1)
is a poorly understood histone modification. Some reports describe
depletion of K27Me1 at promoters and transcription start sites (TSS),
implying its depletion at TSS is necessary for active transcription,
while others have associated enrichment of H3K27me1 at TSS with increased
levels of mRNA expression. Tissue- and gene-specific patterns of
H3K27me1 enrichment and their correlation with gene expression were
determined via chromatin immunoprecipitation on chip microarray (ChIP-chip)
and human mRNA expression array analyses. Results from erythroid
cells were compared with those in neural and muscle cells. H3K27me1
enrichment varied depending on levels of cell-type specific gene
expression, with highest enrichment over transcriptionally active
genes. Over individual genes, the highest levels of H3K27me1 enrichment
were found over the gene bodies of highly expressed genes. In contrast
to H3K4me3, which was highly enriched at the TSS of actively transcribing
genes, H3K27me1 was selectively depleted at the TSS of actively transcribed
genes. There was markedly decreased to no H3K27me1 enrichment in
genes with low expression. At some locations, H3K27 monomethylation
was also found to be associated with chromatin signatures of gene
enhancers.},
doi = {10.1074/jbc.M111.243006},
eprint = {http://www.jbc.org/cgi/reprint/286/45/39457.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/45/39457}
}
@ARTICLE{Steinle2003,
author = {Steinle, Jena J. and Meininger, Cynthia J. and Chowdhury, Usha and
Wu, Guoyao and Granger, Harris J.},
title = {Role of ephrin B2 in human retinal endothelial cell proliferation
and migration},
journal = {Cellular Signalling},
year = {2003},
volume = {15},
pages = {1011--1017},
number = {11},
month = nov,
abstract = {This study was designed to determine the presence of Eph B4 or ephrin
B2 in human retinal endothelial cells (REC) and their signal transduction.
Human retinal endothelial cells were stimulated with an Eph B4/Fc
chimera and probed for phosphorylation of phosphatidylinositol-3-kinase
(PI3K), Src, and mitogen-activated protein kinase (MAPK) pathways.
Proliferation and migration were investigated after Eph B4/Fc stimulation
in the presence of various pathway inhibitors. Human retinal endothelial
cells express ephrin B2, with little expression of Eph B4. Treatment
with EphB4/Fc chimera resulted in activation of PI3K, Src, and MAPK
pathways. Eph B4-stimulated endothelial cell proliferation was mediated
via PI3K, nitric oxide synthase, and extracellular signal-regulated
kinase 1/2 (ERK1/2). Blockade of Src-PI3K pathways produced significant
attenuation of Eph B4/Fc-stimulated migration. These results demonstrate
for the first time that ephrin B2 is present in human retinal endothelial
cells. Additionally, it appears that vascular growth may be modulated
in the retina through activation of the PI3K pathway and its downstream
components.},
issn = {0898-6568},
keywords = {Retina, Endothelial cell, Angiogenesis, Matrix metalloproteinase,
Eye, Blood vessel},
url = {http://www.sciencedirect.com/science/article/B6T2M-48NKTYN-2/2/cf21e3ec3d03354e6fc97270e09b8a82}
}
@ARTICLE{Stella2009,
author = {Stella, Maria Cristina and Trusolino, Livio and Comoglio, Paolo M.},
title = {The Slit/Robo System Suppresses Hepatocyte Growth Factor-dependent
Invasion and Morphogenesis},
journal = {Mol. Biol. Cell},
year = {2009},
volume = {20},
pages = {642--657},
number = {2},
month = jan,
abstract = {The Slit protein acts through the Roundabout receptor as a paracrine
chemorepellent in axon guidance and as an inhibitor in leukocyte
chemotaxis, but its role in epithelial cell motility and morphogenesis
remains largely unexplored. We report that nontransformed epithelial
cells and cancerous cells empower the Slit-2/Robo1 signaling system
to limit outward migration in response to motogenic attractants and
to remain positionally confined within their primitive location.
Short hairpin RNA-mediated depletion of SLIT-2 or ectopic expression
of a soluble decoy Robo enhance hepatocyte growth factor (HGF)-induced
migration, matrix invasion, and tubulogenesis, concomitantly with
the up-regulation of Cdc-42 and the down-modulation of Rac-1 activities.
Accordingly, autocrine overexpression or exogenous administration
of Slit-2 prevent HGF-triggered motile responses, reduce Cdc-42 activation,
and stimulate Rac-1. This antimigratory activity of Slit-2 derives
from the inhibition of actin-based protrusive forces and from an
increased adhesive strength of cadherin-mediated intercellular contacts.
These results disclose a novel function for Slit and Robo in the
inhibition of growth factor-mediated epithelial cell motility and
morphogenesis, invoking a critical role for both molecules as natural
antagonists of neoplastic invasive growth.},
url = {http://www.molbiolcell.org/cgi/content/abstract/20/2/642}
}
@ARTICLE{Stelow2007,
author = {Stelow, Edward B. and Hong, Sueng-Mo and Covell, Jamie L. and Moskaluk,
Christopher A.},
title = {The feasibility of gene expression profiling generated in fine-needle
aspiration specimens from patients with follicular lymphoma and diffuse
large B-cell lymphoma},
journal = {Cancer},
year = {2007},
volume = {111},
pages = {200--201},
number = {3},
issn = {1097-0142},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.22693}
}
@ARTICLE{Stemmer2006,
author = {Stemmer, Kerstin and Ellinger-Ziegelbauer, Heidrun and Lotz, Kerstin
and Ahr, Hans-J. and Dietrich, Daniel R.},
title = {Establishment of a protocol for the gene expression analysis of laser
microdissected rat kidney samples with affymetrix genechips},
journal = {Toxicology and Applied Pharmacology},
year = {2006},
volume = {217},
pages = {134--142},
number = {1},
month = nov,
abstract = {Laser microdissection in conjunction with microarray technology allows
selective isolation and analysis of specific cell populations, e.g.,
preneoplastic renal lesions. To date, only limited information is
available on sample preparation and preservation techniques that
result in both optimal histomorphological preservation of sections
and high-quality RNA for microarray analysis. Furthermore, amplification
of minute amounts of RNA from microdissected renal samples allowing
analysis with genechips has only scantily been addressed to date.
The objective of this study was therefore to establish a reliable
and reproducible protocol for laser microdissection in conjunction
with microarray technology using kidney tissue from Eker rats p.o.
treated for 7 days and 6 months with 10 and 1 mg Aristolochic acid/kg
bw, respectively. Kidney tissues were preserved in RNAlater or snap
frozen. Cryosections were cut and stained with either H&E or cresyl
violet for subsequent morphological and RNA quality assessment and
laser microdissection. RNA quality was comparable in snap frozen
and RNAlater-preserved samples, however, the histomorphological preservation
of renal sections was much better following cryopreservation. Moreover,
the different staining techniques in combination with sample processing
time at room temperature can have an influence on RNA quality. Different
RNA amplification protocols were shown to have an impact on gene
expression profiles as demonstrated with Affymetrix Rat Genome 230_2.0
arrays. Considering all the parameters analyzed in this study, a
protocol for RNA isolation from laser microdissected samples with
subsequent Affymetrix chip hybridization was established that was
also successfully applied to preneoplastic lesions laser microdissected
from Aristolochic acid-treated rats.},
issn = {0041-008X},
keywords = {Laser capture microdissection, Laser microdissection and pressure
catapulting, Kidney, RNA amplification, RNA integrity, Affymetrix,
Microarray},
url = {http://www.sciencedirect.com/science/article/B6WXH-4KKNDVS-1/2/661fd4a00c305816888295b32954e4e6}
}
@ARTICLE{Stenslokken2010,
author = {Stenslokken, Kare-Olav and Ellefsen, Stian and Larsen, Helene Kile
and Vaage, Jarle and Nilsson, Goran E.},
title = {Expression of heat shock proteins in anoxic crucian carp (Carassius
carassius): support for cold as a preparatory cue for anoxia},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2010},
volume = {298},
pages = {R1499--1508},
number = {6},
month = jun,
abstract = {The crucian carp (Carassius carassius) tolerates anoxia for days to
months depending on temperature. During episodes of stress, heat
shock proteins (HSPs) are important for limiting cellular damage,
mainly by ensuring protein function. Accordingly, we hypothesized
that anoxia would change the expression of HSPs and that this response
would be temperature dependent. Real-time RT-PCR was used to investigate
the effects of 1 and 7 days anoxia (A1 and A7) on the expression
of HSP70a, HSP70b, HSC70, HSP90, and HSP30 in the brain and heart
of 8{degrees}C- and 13{degrees}C-acclimated crucian carp. In general,
the expression of all HSPs changed in response to anoxia, although
varying in size and direction, and with organ and temperature. HSP70a
expression increased drastically ([~]10-fold) in A7 brains and hearts
at 13{degrees}C but not at 8{degrees}C. HSC70 and HSP90 expression
decreased in A7 brains (by 60-70%), but not in A7 hearts. HSC70 expression
increased in A1 brains and hearts at both temperatures (by 60-160%),
and HSP30 expression decreased in A7 brains and hearts at both temperatures
(by 50-80%). Notably, normoxic fish showed 7- and 11-fold higher
HSP70a expression in the brain and heart at 8{degrees}C compared
with 13{degrees}C. This difference disappeared during anoxia, suggesting
that cold may function as a cue for preconditioning the crucian carp's
HSP70a expression to the approaching anoxic winter period.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/298/6/R1499}
}
@ARTICLE{Stenslokken2008,
author = {Stenslokken, Kare-Olav and Ellefsen, Stian and Stecyk, Jonathan A.
W. and Dahl, Mai Britt and Nilsson, Goran E. and Vaage, Jarle},
title = {Differential regulation of AMP-activated kinase and AKT kinase in
response to oxygen availability in crucian carp (Carassius carassius)},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2008},
volume = {295},
pages = {R1803--1814},
number = {6},
month = dec,
abstract = {We investigated whether two kinases critical for survival during periods
of energy deficiency in anoxia-intolerant mammalian species, AMP-activated
kinase (AMPK), and protein kinase B (AKT), are equally important
for hypoxic/anoxic survival in the extremely anoxia-tolerant crucian
carp (Carassius carassius). We report that phosphorylation of AMPK
and AKT in heart and brain showed small changes after 10 days of
severe hypoxia (0.3 mg O2/l at 9{degrees}C). In contrast, anoxia
exposure (0.01 mg O2/l at 8{degrees}C) substantially increased AMPK
phosphorylation but decreased AKT phosphorylation in carp heart and
brain, indicating activation of AMPK and deactivation of AKT. In
agreement, blocking the activity of AMPK in anoxic fish in vivo with
20 mg/kg Compound C resulted in an elevated metabolic rate (as indicated
by increased ethanol production) and tended to reduce energy charge.
This is the first in vivo experiment with Compound C in a nonmammalian
vertebrate, and it appears that AMPK plays a role in mediating anoxic
metabolic depression in crucian carp. Real-time RT-PCR analysis of
the investigated AMPK subunit revealed that the most likely composition
of subunits in the carp heart is {alpha}2, {beta}1B, {gamma}2a, whereas
a more even expression of subunits was found in the brain. In the
heart, expression of the regulatory {gamma}2-subunit increased in
the heart during anoxia. In the brain, expression of the {alpha}1-,
{alpha}2-, and {gamma}1-subunits decreased with anoxia exposure,
but expression of the {gamma}2-subunit remained constant. Combined,
our findings suggest that AMPK and AKT may play important, but opposing
roles for hypoxic/anoxic survival in the anoxia-tolerant crucian
carp.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/295/6/R1803}
}
@ARTICLE{Stenvall2005,
author = {Stenvall, Maria and Steen, Johanna and Uhlén, Mathias and Hober,
Sophia and Ottosson, Jenny},
title = {High-throughput solubility assay for purified recombinant protein
immunogens},
journal = {Biochimica et Biophysica Acta (BBA) - Proteins \& Proteomics},
year = {2005},
volume = {1752},
pages = {6--10},
number = {1},
month = aug,
abstract = {A high-throughput assay is described for analysis of the solubility
of purified recombinant proteins. The assay is based on affinity
purification of proteins in the presence of chaotropic agents followed
by a dilution and incubation step to investigate the solubility in
the absence of high concentrations of such agents. The assay can
be performed in a 96-well format, which makes it well suited for
high-throughput applications. For 125 recombinant proteins expressed
as part of an antibody-based proteomics effort, experimental solubility
data were compared to calculated hydrophobicity values based on the
amino acid sequence of each protein. This comparison showed only
weak correlation between the theoretical and experimental values,
which emphasizes the importance of experimental assays to determine
the solubility of recombinant proteins.},
issn = {1570-9639},
keywords = {Protein solubility, High-throughput, In vitro assay, Urea},
url = {http://www.sciencedirect.com/science/article/B73DJ-4GP272J-1/2/18c1b150f632f93b0e79de110c1d069e}
}
@ARTICLE{Stepan2011,
author = {Stepan, Lara P. and Trueblood, Esther S. and Hale, Kari and Babcook,
John and Borges, Luis and Sutherland, Claire L.},
title = {Expression of Trop2 Cell Surface Glycoprotein in Normal and Tumor
Tissues: Potential Implications as a Cancer Therapeutic Target},
journal = {Journal of Histochemistry \& Cytochemistry},
year = {2011},
volume = {59},
pages = {701-710},
number = {7},
abstract = {Trop2 is a cell-surface glycoprotein reported to be overexpressed
in various types of adenocarcinomas with minimal expression in normal
tissues. Recent findings that Trop2 expression correlates with tumor
aggressiveness have increased interest in Trop2 as a potential target
for cancer immunotherapy. The goal of this study was to extensively
evaluate Trop2 expression at the transcript and protein levels in
normal and tumor tissues. It was determined that Trop2 is overexpressed
on some carcinomas relative to the corresponding normal tissue. However,
in human and mouse, Trop2 is highly expressed at both the transcript
and protein levels on several essential normal tissues. The findings
suggest that the development of therapeutic agents to target Trop2
may require strategies that target Trop2 on malignant tissues in
order to minimize potential toxicities to essential normal tissues
that also express high levels of Trop2.},
doi = {10.1369/0022155411410430},
eprint = {http://jhc.sagepub.com/cgi/reprint/59/7/701.pdf},
url = {http://jhc.sagepub.com/cgi/content/abstract/59/7/701}
}
@ARTICLE{Stepanov2008,
author = {Stepanov, Alexander and Nitiss, Karin C. and Neale, Geoffrey and
Nitiss, John L.},
title = {Enhancing Drug Accumulation in Saccharomyces cerevisiae by Repression
of Pleiotropic Drug Resistance Genes with Chimeric Transcription
Repressors},
journal = {Mol. Pharmacol.},
year = {2008},
volume = {74},
pages = {423--431},
number = {2},
month = aug,
abstract = {Yeast is a powerful model system for studying the action of small-molecule
therapeutics. An important limitation has been low efficacy of many
small molecules in yeast due to limited intracellular accumulation.
We used the DNA binding domain of the pleiotropic drug resistance
regulator pleiotropic drug resistance 1 (Pdr1) fused in-frame to
transcription repressors to repress Pdr1-regulated genes. Expression
of these chimeric regulators conferred dominant enhancement of sensitivity
to a different class of compounds and led to greatly diminished levels
of Pdr1p-regulated transcripts, including the yeast p-glycoprotein
homolog Pdr5. Enhanced sensitivity was seen for a wide range of small
molecules. Biochemical measurements demonstrated enhanced accumulation
of rhodamine in yeast cells expressing the chimeric repressors. These
repressors of Pdr1p-regulated transcripts can be introduced into
large collections of strains such as the Saccharomyces cerevisiae
deletion set and enhance the utility of yeast for studying drug action
and for mechanism-based drug discovery.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/74/2/423}
}
@ARTICLE{Stephens2011,
author = {Stephens, Alexandre S. and Stephens, Sebastien R. and Hobbs, Carl
and Hutmacher, Deitmar W. and Bacic-Welsh, Desa and Woodruff, Maria
Ann and Morrison, Nigel A.},
title = {Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified
by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {30071-30086},
number = {34},
abstract = {Rapid mineralization of cultured osteoblasts could be a useful characteristic
in stem cell-mediated therapies for fracture and other orthopedic
problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent
molecule capable of stimulating cell differentiation. We report that,
in primary human osteoblasts, DMSO dose-dependently enhanced the
expression of osteoblast differentiation markers alkaline phosphatase
activity and extracellular matrix mineralization. Furthermore, similar
DMSO-mediated mineralization enhancement was observed in primary
osteoblast-like cells differentiated from mouse mesenchymal cells
derived from fat, a promising source of starter cells for cell-based
therapy. Using a convenient mouse pre-osteoblast model cell line
MC3T3-E1, we further investigated this phenomenon showing that numerous
osteoblast-expressed genes were elevated in response to DMSO treatment
and correlated with enhanced mineralization. Myocyte enhancer factor
2c (Mef2c) was identified as the transcription factor most induced
by DMSO, among the numerous DMSO-induced genes, suggesting a role
for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed
expression of Mef2c in osteoblast-like cells in mouse mandible, cortical,
and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted
in defective osteoblast differentiation, decreased alkaline phosphatase
activity, and matrix mineralization and knockdown of osteoblast specific
gene expression, including osteocalcin and bone sialoprotein. A flow
on knockdown of bone-specific transcription factors, Runx2 and osterix
by shRNAi knockdown of Mef2c, suggests that Mef2c lies upstream of
these two important factors in the cascade of gene expression in
osteoblasts.},
doi = {10.1074/jbc.M111.253518},
eprint = {http://www.jbc.org/cgi/reprint/286/34/30071.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/34/30071}
}
@ARTICLE{Stephens2010a,
author = {Stephens, Kenyatta W. and Hutchins, Rebecca J. and Dauphin, Leslie
A.},
title = {Cross-platform evaluation of commercial real-time reverse transcription
PCR master mix kits using a quantitative 5'nuclease assay for Ebola
virus},
journal = {Molecular and Cellular Probes},
year = {2010},
volume = {24},
pages = {370--375},
number = {6},
month = dec,
abstract = {Selection of optimal reaction master mix reagents is essential to
obtain the best performance with diagnostic real-time reverse transcription
polymerase chain reaction (RT-PCR) assays. Every year the number
of commercially available master mix kits increases, so it is prudent
to periodically evaluate kits on the market. In this study we evaluated
five commercial real-time RT-PCR master mix kits, the RealMasterMix
RT-PCR ROX kit, the AgPath-ID One-Step RT-PCR kit, the SuperScript
III Platinum One-step Quantitative RT-PCR system, the QuantiTect
Probe RT-PCR kit, and the LightCycler RNA HybProbe amplification
kit, using a 5'nuclease assay for Ebola virus. The kits were evaluated
using the manufacturer's recommended conditions, as well as conditions
which have been used with the Ebola virus assay during outbreaks.
When evaluated for use in Ebola virus RNA detection, the AgPath-ID
kit resulted in the greatest sensitivity in comparison to the other
four kits. The efficacy of the AgPath-ID kit was instrument-independent
in the five real-time PCR platforms tested. This study demonstrated
that Ebola virus RNA detection was not equivalent among the master
mix reagents studied and, thus, that this variable can affect real-time
RT-PCR assay sensitivity. Furthermore, this study rates the master
mix reagents for their suitability, providing diagnostic laboratories
the option to select from these kits to suit their specific laboratory
needs for real-time RT-PCR.},
issn = {0890-8508},
keywords = {Master mix, Ebola virus, Real-time RT-PCR, Bioterrorism},
url = {http://www.sciencedirect.com/science/article/B6WNC-50V20BJ-2/2/987aab7cf36ed6535004c2d28ee88a62}
}
@ARTICLE{Stephens2010,
author = {Stephens, Nathan and Gallagher, Iain and Rooyackers, Olav and Skipworth,
Richard and Tan, Ben and Marstrand, Troels and Ross, James and Guttridge,
Denis and Lundell, Lars and Fearon, Kenneth and Timmons, James},
title = {Using transcriptomics to identify and validate novel biomarkers of
human skeletal muscle cancer cachexia},
journal = {Genome Medicine},
year = {2010},
volume = {2},
pages = {1},
number = {1},
abstract = {BACKGROUND:Cancer cachexia is a multi-organ tissue wasting syndrome
that contributes to morbidity and mortality in many cancer patients.
Skeletal muscle loss represents an established key feature yet there
is no molecular understanding of the disease process. In fact, the
postulated molecular regulators of cancer cachexia originate largely
from pre-clinical models and it is unclear how these translate to
the clinical environment.METHODS:Rectus abdominis muscle biopsies
were obtained from 65 upper gastrointestinal (UGI) cancer patients
during open surgery and RNA profiling was performed on a subset of
this cohort (n = 21) using the Affymetrix U133+2 platform. Quantitative
analysis revealed a gene signature, which underwent technical validation
and independent confirmation in a separate clinical cohort.RESULTS:Quantitative
significance analysis of microarrays produced an 83-gene signature
that was able to identify patients with greater than 5% weight loss,
while this molecular profile was unrelated to markers of systemic
inflammation. Selected genes correlating with weight loss were validated
using quantitative real-time PCR and independently studied as general
cachexia biomarkers in diaphragm and vastus lateralis from a second
cohort (n = 13; UGI cancer patients). CaMKIIß correlated positively
with weight loss in all muscle groups and CaMKII protein levels were
elevated in rectus abdominis. TIE1 was also positively associated
with weight loss in both rectus abdominis and vastus lateralis muscle
groups while other biomarkers demonstrated tissue-specific expression
patterns. Candidates selected from the pre-clinical literature, including
FOXO protein and ubiquitin E3 ligases, were not related to weight
loss in this human clinical study. Furthermore, promoter analysis
identified that the 83 weight loss-associated genes had fewer FOXO
binding sites than expected by chance.CONCLUSION:We were able to
discover and validate new molecular biomarkers of human cancer cachexia.
The exercise activated genes CaMKIIß and TIE1 related positively
to weight-loss across muscle groups, indicating that this cachexia
signature is not simply due to patient inactivity. Indeed, excessive
CaMKIIß activation is a potential mechanism for reduced muscle protein
synthesis. Our genomics analysis also supports the view that the
available preclinical models do not accurately reflect the molecular
characteristics of human muscle from cancer cachexia patients.},
doi = {10.1186/gm122},
issn = {1756-994X},
pubmedid = {20193046},
url = {http://genomemedicine.com/content/2/1/1}
}
@ARTICLE{Stephensen2007,
author = {Stephensen, Charles B. and Borowsky, Alexander D. and Lloyd, Kevin
C. Kent},
title = {Disruption of Rxra gene in thymocytes and T lymphocytes modestly
alters lymphocyte frequencies, proliferation, survival and T helper
type 1/type 2 balance},
journal = {Immunology},
year = {2007},
volume = {121},
pages = {484--498},
number = {4},
abstract = {Summary Retinoid X receptor (RXR) agonists, including the vitamin
A metabolite 9-cis retinoic acid, decrease T-lymphocyte apoptosis
and promote T helper type 2 (Th2) development ex vivo. To examine
the in vivo role of RXR-α in T-lymphocyte development and function,
we disrupted the Rxra gene in thymocytes and T lymphocytes using
cyclization recombinase (Cre)-loxP-mediated excision of Rxra exon
4. Expression of Cre was targeted to these cells using the Lck promoter.
Successful disruption of exon 4 was seen in thymus and T lymphocytes.
Mice were healthy and the thymus, spleen and lymph nodes appeared
normal. However, knockout mice had a lower percentage of double-positive
(CD4+Â CD8+) and a higher percentage of double-negative thymocytes
than wild-type mice. The percentage of splenic B lymphocytes was
lower in unimmunized and ovalbumin-immunized knockout mice and the
percentage of T lymphocytes was lower in immunized knockout mice.
Ex vivo proliferation was decreased and apoptosis was increased in
T lymphocytes from knockout mice. Memory CD4+ T lymphocytes from
knockout mice produced more interferon-γ and interleukin-2 (IL-2)
and less IL-5 and IL-10 than memory cells from wild-type mice, indicating
a Th1 bias in vivo. However, Rxra disruption did not similarly bias
ex vivo differentiation of naive CD4+ T lymphocytes, nor did Rxra
disruption alter the serum immunoglobulin G1/immunoglobulin G2a response
to immunization. In summary, disruption of Rxra altered the percentages
of T and B lymphocytes, produced a Th1 bias in vivo, and altered
T-lymphocyte proliferation and apoptosis ex vivo. These differences
were modest in magnitude and their impact on disease resistance is
yet to be examined.},
issn = {1365-2567},
keywords = {knockout mice, retinoid X receptor-α, T helper type 1/T helper type
2, T lymphocyte, vitamin A},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2007.02595.x}
}
@ARTICLE{Sterbis2008,
author = {Sterbis, Joseph R. and Gao, Chunling and Furusato, Bungo and Chen,
Yongmei and Shaheduzzaman, Syed and Ravindranath, Lakshmi and Osborn,
David J. and Rosner, Inger L. and Dobi, Albert and McLeod, David
G. and Sesterhenn, Isabell A. and Srivastava, Shiv and Cullen, Jennifer
and Petrovics, Gyorgy},
title = {Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in
Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {758--763},
number = {3},
month = feb,
abstract = {Purpose: Alterations of the androgen receptor (AR)-mediated signaling
through numerous mechanisms are increasingly recognized in prostate
cancer (CaP) progression. We hypothesized that the assessment of
well-defined AR transcriptional targets (e.g., PSA/HK3 mRNA) in CaP
tissues will provide in vivo readout of AR dysfunctions. Moreover,
quantitative expression features of PSA/HK3 mRNA in prostate tumor
cells may serve as a prognostic indicator of disease progression.
Experimental Design: Paired benign and malignant epithelial cells
(242 specimens) were obtained from laser capture microdissection
of frozen OCT-embedded tissue sections prepared from radical prostatectomy
specimens of 121 patients. Quantitative expression of PSA/HK3 mRNA
in the matched malignant and benign cells was analyzed by real-time
reverse transcription-PCR. Results: CaP cells express significantly
lower PSA/HK3 mRNA levels than matched benign cells (P = 0.0133).
Moreover, low PSA/HK3 mRNA expression in malignant cells was associated
with increased risk of biochemical recurrence (P = 0.0217), as well
as with time to recurrence (P = 0.0371), in patients with intermediate
preoperative serum prostate-specific antigen levels (2-10 ng/mL).
The expression of androgen-dependent genes in clinical samples correlates
with each other in patients with higher expression of PSA/HK3 mRNA
but not in patients with lower expression of PSA/HK3 mRNA reflecting
AR pathway dysfunction. Conclusions: Our study has unraveled a novel
prognostic utility of quantitative measurements of PSA/HK3 mRNA reflecting
AR transcriptional activity in CaP cells, which is independent of
serum prostate-specific antigen. It also has potential in stratifying
subsets of patients exhibiting progressive disease associated with
dampened AR transcriptional functions who may be targeted by tailored
therapeutic strategies.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/3/758}
}
@ARTICLE{Stergiopoulos2009,
author = {Stergiopoulos, Konstantinos and Cabrero, Pablo and Davies, Shireen-Anne
and Dow, Julian A. T.},
title = {Salty dog, an SLC5 symporter, modulates Drosophila response to salt
stress},
journal = {Physiol Genomics},
year = {2009},
volume = {37},
pages = {1--11},
number = {1},
month = mar,
abstract = {To regulate their internal environments, organisms must adapt to varying
ion levels in their diet. Adult Drosophila were exposed to dietary
salt stress, and their physiological, survival, and gene expression
responses monitored. Insects continued to feed on NaCl-elevated diet,
although levels >4% wt/vol ultimately proved fatal. Affymetrix microarray
analysis of flies fed on diet containing elevated NaCl showed a phased
response: the earliest response was widespread upregulation of immune
genes, followed by upregulation of carbohydrate metabolism as the
immune response was downregulated, then finally a switch to amino
acid catabolism and inhibition of genes associated with the reproductive
axis. Significantly, the online transcriptomic resource FlyAtlas
reports that most of the modulated genes are predominantly expressed
in hindgut or Malpighian (renal) tubule, implicating these excretory
tissues as the major responders to salt stress. Three genes were
selected for further study: the SLC5 symporter CG2196, the GLUT transporter
CG6484, and the transcription factor sugarbabe (previously implicated
in starvation and stress responses). Expression profiles predicted
by microarray were validated by quantitative PCR (qPCR); expression
was mapped to the alimentary canal by in situ hybridization. CG2196::eYFP
overexpression constructs were localized to the basolateral membrane
of the Malpighian (renal) tubules, and RNAi against CG2196 improved
survival on high-salt diet, even when driven specifically to just
principal cells of the Malpighian tubule, confirming both this tissue
and this transporter as major determinants of survival upon salt
stress. Accordingly, CG2196 was renamed salty dog (salt).},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/37/1/1}
}
@ARTICLE{Sterling2004,
author = {Sterling, James D.},
title = {Laboratory automation curriculum at Keck Graduate Institute},
journal = {Journal of the Association for Laboratory Automation},
year = {2004},
volume = {9},
pages = {331--335},
number = {5},
month = oct,
abstract = {A novel curriculum in laboratory automation and high-throughput technologies
has been developed at the Keck Graduate Institute (KGI) over the
past five years as part of the professional masters degree program
in applied life sciences. The goal of this curriculum has been four-fold:
(1) motivate study by describing the need for automation through
several example problems in combinatorial biological discovery, (2)
provide elements of fundamental engineering science that are required
for the development of the technologies and tools that enable automation,
(3) provide opportunities for the students to see and use state-of-the-art
instruments, learn about existing industry standards, and to visit
integrated laboratories that perform high-throughput research, and
(4) introduce scientific discoveries and new technologies that could
have future impact on laboratory automation and discuss current trends,
and project future trends in this field.},
issn = {1535-5535},
keywords = {automation, high-throughput screening, life sciences curriculum, bioengineering
curriculum, automation education},
url = {http://www.sciencedirect.com/science/article/B75DF-4DGSX88-H/2/15edaca99b9d6f90a4065a1e346f358d}
}
@ARTICLE{Stern2009,
author = {Stern, Michael Zeev and Gupta, Sachin Kumar and Salmon-Divon, Mali
and Haham, Tomer and Barda, Omer and Levi, Sarit and Wachtel, Chaim
and Nilsen, Timothy W. and Michaeli, Shulamit},
title = {Multiple roles for polypyrimidine tract binding (PTB) proteins in
trypanosome RNA metabolism},
journal = {RNA},
year = {2009},
volume = {15},
pages = {648--665},
number = {4},
month = apr,
abstract = {Trypanosomatid genomes encode for numerous proteins containing an
RNA recognition motif (RRM), but the function of most of these proteins
in mRNA metabolism is currently unknown. Here, we report the function
of two such proteins that we have named PTB1 and PTB2, which resemble
the mammalian polypyrimidine tract binding proteins (PTB). RNAi silencing
of these factors indicates that both are essential for life. PTB1
and PTB2 reside mostly in the nucleus, but are found in the cytoplasm,
as well. Microarray analysis performed on PTB1 and PTB2 RNAi silenced
cells indicates that each of these factors differentially affects
the transcriptome, thus regulating a different subset of mRNAs. PTB1
and PTB2 substrates were categorized bioinformatically, based on
the presence of PTB binding sites in their 5' and 3' flanking sequences.
Both proteins were shown to regulate mRNA stability. Interestingly,
PTB proteins are essential for trans-splicing of genes containing
C-rich polypyrimidine tracts. PTB1, but not PTB2, also affects cis-splicing.
The specificity of binding of PTB1 was established in vivo and in
vitro using a model substrate. This study demonstrates for the first
time that trans-splicing of only certain substrates requires specific
factors such as PTB proteins for their splicing. The trypanosome
PTB proteins, like their mammalian homologs, represent multivalent
RNA binding proteins that regulate mRNAs from their synthesis to
degradation.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/15/4/648}
}
@ARTICLE{Stern-Straeter2011,
author = {Stern-Straeter, Jens and Bonaterra, Gabriel Alejandro and Kassner,
Stefan S. and Zügel, Stefanie and Hörmann, Karl and Kinscherf,
Ralf and Goessler, Ulrich Reinhart},
title = {Characterization of human myoblast differentiation for tissue-engineering
purposes by quantitative gene expression analysis},
journal = {Journal of Tissue Engineering and Regenerative Medicine},
year = {2011},
volume = {5},
pages = {e197--e206},
number = {8},
abstract = {Tissue engineering of skeletal muscle is an encouraging possibility
for the treatment of muscle loss through the creation of functional
muscle tissue in vitro from human stem cells. Currently, the preferred
stem cells are primary, non-immunogenic satellite cells ( = myoblasts).
The objective of this study was to determine the expression patterns
of myogenic markers within the human satellite cell population during
their differentiation into multinucleated myotubes for an accurate
characterization of stem cell behaviour. Satellite cells were incubated
(for 1, 4, 8, 12 or 16 days) with a culture medium containing either
a low [ = differentiation medium (DM)] or high [ = growth medium
(GM)] concentration of growth factors. Furthermore, we performed
a quantitative gene expression analysis of well-defined differentiation
makers: myogenic factor 5 (MYF5), myogenin (MYOG), skeletal muscle
αactin1 (ACTA1), embryonic (MYH3), perinatal (MYH8) and adult skeletal
muscle myosin heavy chain (MYH1). Additionally, the fusion indices
of forming myotubes of MYH1, MYH8 and ACTA1 were calculated. We show
that satellite cells incubated with DM expressed multiple characteriztic
features of mature skeletal muscles, verified by time-dependent upregulation
of MYOG, MYH1, MYH3, MYH8 and ACTA1. However, satellite cells incubated
with GM did not reveal all morphological aspects of muscle differentiation.
Immunocytochemical investigations with antibodies directed against
the differentiation markers showed correlations between the gene
expression and differentiation. Our data provide information about
time-dependent gene expression of differentiation markers in human
satellite cells, which can be used for maturation analyses in skeletal
muscle tissue-engineering applications. Copyright © 2011 John Wiley
& Sons, Ltd.},
doi = {10.1002/term.417},
issn = {1932-7005},
keywords = {real-time PCR, reference gene, skeletal muscle, satellite cells, differentiation},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/term.417}
}
@ARTICLE{Stern-Straeter2009,
author = {Stern-Straeter, Jens and Bonaterra, Gabriel and Hörmann, Karl and
Kinscherf, Ralf and Goessler, Ulrich},
title = {Identification of valid reference genes during the differentiation
of human myoblasts},
journal = {BMC Molecular Biology},
year = {2009},
volume = {10},
pages = {66},
number = {1},
abstract = {BACKGROUND:Analysis of RNA expression using real-time PCR (qRT-PCR)
traditionally includes reference genes (RG) as an internal control.
This practice is being questioned as it becomes increasingly clear
that RG may vary considerably under certain experimental conditions.
Thus, the validity of a particular RG must be determined for each
experimental setting. We used qRT-PCR to measure the levels of six
RG, which have been reported in the literature to be invariant. The
RG were analyzed in human myoblast cultures under differentiation
conditions. We examined the expression by qRT-PCR of mRNA encoding
Beta-actin (ACTB), Beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate
dehydrogenase (GAPDH), peptidylprolyl isomerase A (PPIA), TATA box
binding protein (TBP) and ribosomal protein, large, P0 (RPLPO). The
mRNA expression of the following genes of interest (GOI) were analyzed:
skeletal muscle alpha 1 actin (ACTA1), myogenin/myogenic factor 4
(MYOG), embryonic skeletal muscle myosin heavy chain 3 (MYH3) and
the activity of creatine phosphokinase (CK). The geNorm, NormFinder
and BestKeeper software programs were used to ascertain the most
suitable RG to normalize the RNA input.RESULTS:Using the geNorm program,
RPLPO and TBP were found to be the most stable genes, additionally
a suitable normalization factor (NF) was calculated. The NormFinder
software showed that RPLPO was the most stable, whereas TBP ranked
second. BestKeeper program also revealed that RPLPO and TBP as stable
genes, but PPIA was the most stable reference gene, whereas GAPDH
and ACTB were the worst ranked.CONCLUSION:RNA expression analyses
including three independent softwares revealed that RPLPO, TBP as
reference genes or NF calculated by geNorm software, are suitable
to normalize the mRNA expression in myoblast after culture under
differentiation conditions. Significant correlations can be identified
between the differentiations markers ACTA1, MYOG, MYH3 and creatine
phosphokinase (CK) activity, when the expression is normalized with
the NF calculated with RPLPO and TBP.},
doi = {10.1186/1471-2199-10-66},
issn = {1471-2199},
pubmedid = {19573231},
url = {http://www.biomedcentral.com/1471-2199/10/66}
}
@ARTICLE{Sternberg2012,
author = {Sternberg, Katrin and Gratz, Matthias and Koeck, Kathleen and Mostertz,
Joerg and Begunk, Robert and Loebler, Marian and Semmling, Beatrice
and Seidlitz, Anne and Hildebrandt, Petra and Homuth, Georg and Grabow,
Niels and Tuemmler, Conny and Weitschies, Werner and Schmitz, Klaus-Peter
and Kroemer, Heyo K.},
title = {Magnesium used in bioabsorbable stents controls smooth muscle cell
proliferation and stimulates endothelial cells in vitro},
journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials},
year = {2012},
volume = {100B},
pages = {41--50},
number = {1},
abstract = {Magnesium-based bioabsorbable cardiovascular stents have been developed
to overcome limitations of permanent metallic stents, such as late
stent thrombosis. During stent degradation, endothelial and smooth
muscle cells will be exposed to locally high magnesium concentrations
with yet unknown physiological consequences. Here, we investigated
the effects of elevated magnesium concentrations on human coronary
artery endothelial and smooth muscle cell (HCAEC, HCASMC) growth
and gene expression. In the course of 24 h after incubation with
magnesium chloride solutions (1 or 10 mM) intracellular magnesium
level in HCASMC raised from 0.55 ± 0.25 mM (1 mM) to 1.38 ± 0.95
mM (10 mM), while no increase was detected in HCAEC. Accordingly,
a DNA microarray-based study identified 69 magnesium regulated transcripts
in HCAEC, but 2172 magnesium regulated transcripts in HCASMC. Notably,
a significant regulation of various growth factors and extracellular
matrix components was observed. In contrast, viability and proliferation
of HCAEC were increased at concentrations of up to 25 mM magnesium
chloride, while in HCASMC viability and proliferation appeared to
be unaffected. Taken together, our data indicate that magnesium halts
smooth muscle cell proliferation and stimulates endothelial cell
proliferation, which might translate into a beneficial effect in
the setting of stent associated vascular injury. © 2011 Wiley Periodicals,
Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.},
doi = {10.1002/jbm.b.31918},
issn = {1552-4981},
keywords = {magnesium, bioabsorbable metal stent, stent, in-stent restenosis,
cell cycle},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jbm.b.31918}
}
@ARTICLE{Sternberg2011,
author = {Robin M. Sternberg and Kara R. Thoemke and Joseph J. Korte and Scott
M. Moen and Jessica M. Olson and Lisa Korte and Joseph E. Tietge
and Sigmund J. Degitz Jr.},
title = {Control of pituitary thyroid-stimulating hormone synthesis and secretion
by thyroid hormones during Xenopus metamorphosis},
journal = {General and Comparative Endocrinology},
year = {2011},
volume = {173},
pages = {428 - 437},
number = {3},
abstract = {We used ex vivo and in vivo experiments with Xenopus laevis tadpoles
to examine the hypothesis that the set-point for negative feedback
on pituitary thyroid-stimulating hormone (TSH) synthesis and secretion
by thyroid hormones (THs) increases as metamorphosis progresses to
allow for the previously documented concomitant increase in serum
TH concentrations and pituitary TSH mRNA expression during this transformative
process. First, pituitaries from climactic tadpoles were cultured
for up to 96 h to characterize the ability of pituitary explants
to synthesize and secrete TSHβ in the absence of hypothalamic and
circulating hormones. Next, pituitary explants from tadpoles NF stages
54–66 were exposed to physiologically-relevant concentrations of
THs to determine whether stage-specific differences exist in pituitary
sensitivity to negative feedback by THs. Finally, in vivo exposures
of tadpoles to THs were conducted to confirm the results of the ex
vivo experiments. When pituitaries from climactic tadpoles were removed
from the influence of endogenous hormones, TSHβ mRNA expression
increased late or not at all whereas the rate of TSHβ secreted into
media increased dramatically, suggesting that TSH secretion, but
not TSH mRNA expression, is under the negative regulation of an endogenous
signal during the climactic stages of metamorphosis. Pituitaries
from pre- and prometamorphic tadpoles were more sensitive to TH-induced
inhibition of TSHβ mRNA expression and secretion than pituitaries
from climactic tadpoles. The observed decrease in sensitivity of
pituitary TSHβ mRNA expression to negative feedback by THs from
premetamorphosis to metamorphic climax was confirmed by in vivo experiments
in which tadpoles were reared in water containing THs. Based on the
results of this study, a model is proposed to explain the seemingly
paradoxical, concurrent rise in serum TH concentrations and pituitary
TSH mRNA expression during metamorphosis in larval anurans.},
doi = {10.1016/j.ygcen.2011.06.020},
issn = {0016-6480},
keywords = {Hypothalamo-pituitary-thyroid (HPT) axis},
url = {http://www.sciencedirect.com/science/article/pii/S0016648011002668}
}
@ARTICLE{Sterne-Weiler2011,
author = {Sterne-Weiler, Timothy and Howard, Jonathan and Mort, Matthew and
Cooper, David N. and Sanford, Jeremy R.},
title = {Loss of exon identity is a common mechanism of human inherited disease},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1563-1571},
number = {10},
abstract = {It is widely accepted that at least 10% of all mutations causing human
inherited disease disrupt splice-site consensus sequences. In contrast
to splice-site mutations, the role of auxiliary cis-acting elements
such as exonic splicing enhancers (ESE) and exonic splicing silencers
(ESS) in human inherited disease is still poorly understood. Here
we use a top-down approach to determine rates of loss or gain of
known human exonic splicing regulatory (ESR) sequences associated
with either disease-causing mutations or putatively neutral single
nucleotide polymorphisms (SNPs). We observe significant enrichment
toward loss of ESEs and gain of ESSs among inherited disease-causing
variants relative to neutral polymorphisms, indicating that exon
skipping may play a prominent role in aberrant gene regulation. Both
computational and biochemical approaches underscore the relevance
of exonic splicing enhancer loss and silencer gain in inherited disease.
Additionally, we provide direct evidence that both SRp20 (SRSF3)
and possibly PTB (PTBP1) are involved in the function of a splicing
silencer that is created de novo by a total of 83 different inherited
disease mutations in 67 different disease genes. Taken together,
we find that [~]25% (7154/27,681) of known mis-sense and nonsense
disease-causing mutations alter functional splicing signals within
exons, suggesting a much more widespread role for aberrant mRNA processing
in causing human inherited disease than has hitherto been appreciated.},
doi = {10.1101/gr.118638.110},
eprint = {http://genome.cshlp.org/cgi/reprint/21/10/1563.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/10/1563}
}
@ARTICLE{Sterneckert2010,
author = {Sterneckert, Jared and Stehling, Martin and Bernemann, Christof and
Araúzo-Bravo, Marcos J. and Greber, Boris and Gentile, Luca and
Ortmeier, Claudia and Sinn, Martina and Wu, Guangming and Ruau, David
and Zenke, Martin and Brintrup, Rhea and Klein, Diana C. and Ko,
Kinarm and Schöler, Hans R.},
title = {Neural Induction Intermediates Exhibit Distinct Roles of Fgf Signaling},
journal = {STEM CELLS},
year = {2010},
volume = {28},
pages = {1772--1781},
number = {10},
abstract = {Abstract Formation of the neural plate is an intricate process in
early mammalian embryonic development mediated by cells of the inner
cell mass and involving a series of steps, including development
of the epiblast. Here, we report on the creation of an embryonic
stem (ES) cell-based system to isolate and identify neural induction
intermediates with characteristics of epiblast cells and neural plate.
We demonstrate that neural commitment requires prior differentiation
of ES cells into epiblast cells that are indistinguishable from those
derived from natural embryos. We also demonstrate that epiblast cells
can be isolated and cultured as epiblast stem cell lines. Fgf signaling
is shown to be required for the differentiation of ES cells into
these epiblast cells. Fgf2, widely used for maintenance of both human
ES cells and epiblast stem cells, inhibits formation of early neural
cells by epiblast intermediates in a dose-dependent manner and is
sufficient to promote transient self-renewal of epiblast stem cells.
In contrast, Fgf8, the endogenous embryonic neural inducer, fails
to promote epiblast self-renewal, but rather promotes more homogenous
neural induction with transient self-renewal of early neural cells.
Removal of Fgf signaling entirely from epiblast cells promotes rapid
neural induction and subsequent neurogenesis. We conclude that Fgf
signaling plays different roles during the differentiation of ES
cells, with an initial requirement in epiblast formation and a subsequent
role in self-renewal. Fgf2 and Fgf8 thus stimulate self-renewal in
different cell types. STEM CELLS 2010;28:1772–1781},
issn = {1549-4918},
keywords = {Embryonic stem cells, Neural induction, Pluripotent stem cells, Neural
differentiation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/stem.498}
}
@ARTICLE{Sterrenburg2004,
author = {Sterrenburg, Ellen and Turk, Rolf and 't Hoen, Peter A. C. and van
Deutekom, Judith C. T. and Boer, Judith M. and van Ommen, Gert-Jan
B. and den Dunnen, Johan T.},
title = {Large-scale gene expression analysis of human skeletal myoblast differentiation},
journal = {Neuromuscular Disorders},
year = {2004},
volume = {14},
pages = {507--518},
number = {8-9},
month = sep,
abstract = {To study pathways involved in human skeletal myogenesis, we profiled
gene expression in human primary myoblast cells derived from three
individuals using both oligonucleotide and cDNA microarrays. Following
stringent statistical testing (false-positive rate 0.4%), we identified
146 genes differentially expressed over time. Interestingly, 86 of
these genes have not been reported to be involved in myogenesis in
mouse cell lines. This demonstrates the additional value of human
primary cell cultures in the study of muscle differentiation. Many
of the identified genes play a role in muscle regeneration, indicating
the close relationship of this process with muscle development. In
addition, we found overlap with expression profiling studies in muscle
from Duchenne muscular dystrophy patients, confirming ongoing muscle
regeneration in Duchenne muscular dystrophy. Further study of these
genes can bring new insights into the process of muscle differentiation,
and they are candidate genes for neuromuscular disorders with an
as yet unidentified cause.},
issn = {0960-8966},
keywords = {Myogenesis, Muscle differentiation, Gene expression, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T9T-4CHRDCB-4/2/683edecd290e8d628830d15801cc82d7}
}
@ARTICLE{Sterrenburg2006,
author = {Sterrenburg, Ellen and van der Wees, Caroline G.C. and White, Stefan
J. and Turk, Rolf and de Menezes, Renée X. and van Ommen, Gert-Jan
B. and den Dunnen, Johan T. and 't Hoen, Peter A.C.},
title = {Gene expression profiling highlights defective myogenesis in DMD
patients and a possible role for bone morphogenetic protein 4},
journal = {Neurobiology of Disease},
year = {2006},
volume = {23},
pages = {228--236},
number = {1},
month = jul,
abstract = {Duchenne Muscular Dystrophy (DMD) is characterized by progressive
muscle weakness and wasting. Despite the sustained presence of satellite
cells in their skeletal muscles, muscle regeneration in DMD patients
seems inefficient and unable to compensate for the continuous muscle
fiber loss. To find a molecular explanation, we compared the gene
expression profiles of myoblasts from healthy individuals and DMD
patients during activation and differentiation in culture. DMD cultures
showed significant gene expression changes, even before dystrophin
is expressed. We found a higher expression level of bone morphogenetic
protein 4 (BMP4) in DMD cultures, which we demonstrate to inhibit
differentiation into myotubes. In the later stages of differentiation,
we observed a significant decline in expression of sarcomeric genes
in the absence of dystrophin, probably contributing to sarcomeric
instability. These results support the hypothesis that inefficient
muscle regeneration is caused by impaired myoblast differentiation
and impaired maintenance of the myotubes.},
issn = {0969-9961},
url = {http://www.sciencedirect.com/science/article/B6WNK-4JWMT3K-2/2/dcb589d1867e62bffc3748a3208d495c}
}
@ARTICLE{Stettner2007,
author = {Stettner, Mark and Kaulfuss, Silke and Burfeind, Peter and Schweyer,
Stefan and Strauss, Arne and Ringert, Rolf-Hermann and Thelen, Paul},
title = {The relevance of estrogen receptor-{beta} expression to the antiproliferative
effects observed with histone deacetylase inhibitors and phytoestrogens
in prostate cancer treatment},
journal = {Mol. Cancer Ther.},
year = {2007},
volume = {6},
pages = {2626--2633},
number = {10},
month = oct,
abstract = {In the prostate, estrogen receptor {beta} (ER{beta}), the preferred
receptor for phytoestrogens, has features of a tumor suppressor.
To investigate the mechanisms underlying the beneficial effects on
prostate cancer of histone deacetylase inhibitor valproic acid (VPA)
and phytoestrogen tectorigenin, we analyzed the expression of ER{beta}
after tectorigenin or VPA treatment. For further functional analysis,
we knocked down ER{beta} expression by RNA interference. LNCaP prostate
cancer cells were treated with 5 mmol/L VPA or 100 {micro}mol/L tectorigenin
and transfected with small interfering RNA (siRNA) against ER{beta}.
Control transfections were done with luciferase (LUC) siRNA. Expression
of ER{beta} was assessed by Western blot. mRNA expression was quantitated
by real-time reverse transcription-PCR. Expression of ER{beta} mRNA
and protein markedly increased after VPA or tectorigenin treatment.
When ER{beta} was knocked down by siRNA, the expression of prostate-derived
Ets factor, prostate-specific antigen, prostate cancer-specific indicator
gene DD3PCA3, insulin-like growth factor-1 receptor, the catalytic
subunit of the telomerase, and ER{alpha} was up-regulated and the
tectorigenin effects were abrogated. ER{beta} levels were diminished
in prostate cancer and loss of ER{beta} was associated with proliferation.
Here, we show that siRNA-mediated knockdown of ER{beta} increases
the expression of genes highly relevant to tumor cell proliferation.
In addition, we show that one prominent result of treatment with
VPA or tectorigenin is the up-regulation of ER{beta} resulting in
antiproliferative effects. Thus, these drugs, by restoring the regulatory
function of ER{beta} in tumor cells, could become useful in the intervention
of prostate cancer. [Mol Cancer Ther 2007;6(10):2626-33]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/6/10/2626}
}
@ARTICLE{Steuerwald2010,
author = {Steuerwald, Nury M. and Parsons, Judith C. and Bennett, Kristen and
Bates, Tonya C. and Bonkovsky, Herbert L.},
title = {Parallel microRNA and mRNA expression profiling of (genotype 1b)
human hepatoma cells expressing hepatitis C virus},
journal = {Liver International},
year = {2010},
volume = {30},
pages = {1490--1504},
number = {10},
abstract = {Abstract Background & aims: MicroRNAs (miRNAs) are members of a class
of small noncoding functional RNAs that modulate gene regulation
at the post-transcriptional level in a sequence specific manner.
miRNA dysfunction has been linked to the pathophysiology of human
diseases including those resulting from viral infections. The objective
of this study was to investigate changes in miRNA profiles that occur
in hepatoma cells expressing hepatitis C virus (HCV) and identify
anticorrelated mRNAs, which may be their regulatory targets. Methods:
Microarrays were used to perform global miRNA and mRNA expression
analysis. Fold changes and pairwise statistics were computed for
the resulting datasets. Hierarchical cluster and pathway analyses
were performed to assess the degree of differential expression and
identify regulatory networks. Bioinformatics tools were used to integrate
mRNA profiling results with miRNA target predictions. Results: Replication
of the Con1 strain of HCV virus in hepatoma cells elicited extensive
differential expression of both miRNAs and mRNAs. Forty-three differentially
expressed miRNAs (P≤0.001) were identified by microarray analysis
in HCV expressing cells. Six thousand eight hundred and fifteen differentially
expressed mRNAs (P≤0.05) were identified. Computational analyses
revealed anticorrelated miRNA:mRNA pairs for each target prediction
algorithm used. Pathway analysis generated a filtered pathway with
120 entities, including seven major regulators and nine major targets
potentially under the control of at least 11 miRNAs. Conclusions:
The expression of a number of anticorrelated miRNAs:mRNA pairs are
affected by the presence of HCV. These miRNAs and their putative
targets are attractive candidates for being involved in the pathogenesis
and/or progression of HCV-induced chronic hepatitis.},
issn = {1478-3231},
keywords = {Con1, hepatitis C virus, microarray, microRNA, mRNA, systems biology},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1478-3231.2010.02321.x}
}
@ARTICLE{Stevanato2009,
author = {Stevanato, Lara and Corteling, Randolph and Stroemer, Paul and Hope,
Andrew and Heward, Julie and Miljan, Erik and Sinden, John},
title = {c-MycERTAM transgene silencing in a genetically modified human neural
stem cell line implanted into MCAo rodent brain},
journal = {BMC Neuroscience},
year = {2009},
volume = {10},
pages = {86},
number = {1},
abstract = {BACKGROUND:The human neural stem cell line CTX0E03 was developed for
the cell based treatment of chronic stroke disability. Derived from
fetal cortical brain tissue, CTX0E03 is a clonal cell line that contains
a single copy of the c-mycERTAM transgene delivered by retroviral
infection. Under the conditional regulation by 4-hydroxytamoxifen
(4-OHT), c-mycERTAM enabled large-scale stable banking of the CTX0E03
cells. In this study, we investigated the fate of this transgene
following growth arrest (EGF, bFGF and 4-OHT withdrawal) in vitro
and following intracerebral implantation into a mid-cerebral artery
occluded (MCAo) rat brain. In vitro, 4-weeks after removing growth
factors and 4-OHT from the culture medium, c-mycERTAM transgene transcription
is reduced by ~75%. Furthermore, immunocytochemistry and western
blotting demonstrated a concurrent decrease in the c-MycERTAM protein.
To examine the transcription of the transgene in vivo, CTX0E03 cells
(450,000) were implanted 4-weeks post MCAo lesion and analysed for
human cell survival and c-mycERTAM transcription by qPCR and qRT-PCR,
respectively.RESULTS:The results show that CTX0E03 cells were present
in all grafted animal brains ranging from 6.3% to 39.8% of the total
cells injected. Prior to implantation, the CTX0E03 cell suspension
contained 215.7 (SEM = 13.2) copies of the c-mycERTAM transcript
per cell. After implantation the c-mycERTAM transcript copy number
per CTX0E03 cell had reduced to 6.9 (SEM = 3.4) at 1-week and 7.7
(SEM = 2.5) at 4-weeks. Bisulfite genomic DNA sequencing of the in
vivo samples confirmed c-mycERTAM silencing occurred through methylation
of the transgene promoter sequence.CONCLUSION:In conclusion the results
confirm that CTX0E03 cells downregulated c-mycERTAM transgene expression
both in vitro following EGF, bFGF and 4-OHT withdrawal and in vivo
following implantation in MCAo rat brain. The silencing of the c-mycERTAM
transgene in vivo provides an additional safety feature of CTX0E03
cells for potential clinical application.},
doi = {10.1186/1471-2202-10-86},
issn = {1471-2202},
pubmedid = {19622162},
url = {http://www.biomedcentral.com/1471-2202/10/86}
}
@ARTICLE{Stevens2010a,
author = {Stevens, Jonathan and Ermakov, Alexander and Braganca, Jose and Hilton,
Helen and Underhill, Peter and Bhattacharya, Shoumo and Brown, Nigel
and Norris, Dominic},
title = {Analysis of the asymmetrically expressed Ablim1 locus reveals existence
of a lateral plate Nodal-independent left sided signal and an early,
left-right independent role for nodal flow},
journal = {BMC Developmental Biology},
year = {2010},
volume = {10},
pages = {54},
number = {1},
abstract = {BACKGROUND:Vertebrates show clear asymmetry in left-right (L-R) patterning
of their organs and associated vasculature. During mammalian development
a cilia driven leftwards flow of liquid leads to the left-sided expression
of Nodal, which in turn activates asymmetric expression of the transcription
factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric
morphogenesis, it is clear from published data that additional asymmetrically
expressed loci must exist.RESULTS:A L-R expression screen identified
the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1),
as asymmetrically expressed in both the node and left lateral plate
mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly,
Ablim1 LPM asymmetry was detected in the absence of detectable Nodal.
In the node, Ablim1 was initially expressed symmetrically across
the entire structure, resolving to give a peri-nodal ring at the
headfold stage in a flow and Pkd2-dependent manner. The peri-nodal
ring of Ablim1 expression became asymmetric by the mid-headfold stage,
showing stronger right than left-sided expression. Node asymmetry
became more apparent as development proceeded; expression retreated
in an anticlockwise direction, disappearing first from the left anterior
node. Indeed, at early somite stages Ablim1 shows a unique asymmetric
expression pattern, in the left lateral plate and to the right side
of the node.CONCLUSION:Left LPM Ablim1 is expressed in the absence
of detectable LPM Nodal, clearly revealing existence of a Pitx2 and
Nodal-independent left-sided signal in mammals. At the node, a previously
unrecognised action of early nodal flow and Pkd2 activity, within
the pit of the node, influences gene expression in a symmetric manner.
Subsequent Ablim1 expression in the peri-nodal ring reveals a very
early indication of L-R asymmetry. Ablim1 expression analysis at
the node acts as an indicator of nodal flow. Together these results
make Ablim1 a candidate for controlling aspects of L-R identity and
patterning.},
doi = {10.1186/1471-213X-10-54},
issn = {1471-213X},
pubmedid = {20487527},
url = {http://www.biomedcentral.com/1471-213X/10/54}
}
@ARTICLE{Stevens2010,
author = {Stevens, Marc J. A. and Molenaar, Douwe and de Jong, Anne and De
Vos, Willem M. and Kleerebezem, Michiel},
title = {{sigma}54-mediated control of the mannose phosphotransferase sytem
in Lactobacillus plantarum impacts on carbohydrate metabolism},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {695--707},
number = {3},
month = mar,
abstract = {Sigma factors direct specific binding of the bacterial RNA polymerase
to the promoter. Here we present the elucidation of the{sigma} 54
regulon in Lactobacillus plantarum. A sequence-based regulon prediction
of{sigma} 54-dependent promoters revealed an operon encoding a mannose
phosphotransferase system (PTS) as the best candidate for{sigma}
54-mediated control. A{sigma} 54 (rpoN) mutant derivative did not
grow on mannose, confirming this prediction. Additional mutational
analyses established the presence of one functional mannose PTS in
L. plantarum, the expression of which is controlled by{sigma} 54
in concert with the {sigma}54-activator ManR. Genome-wide transcription
comparison of the wild-type and the rpoN-deletion strain revealed
nine upregulated genes in the wild-type, including the genes of the
mannose PTS, and 21 upregulated genes in the rpoN mutant. The{sigma}
54-controlled mannose PTS was shown also to transport glucose in
L. plantarum wild-type cells, and its presence causes a lag phase
when cultures are transferred from glucose- to galactose-containing
media. The mannose PTS appeared to drain phosphoenolpyruvate (PEP)
pools in resting cells, since no PEP could be detected in resting
wild-type cells, while mannose PTS mutant derivatives contained 1-3
{micro}M PEP (mg protein)-1. Our data provide new insight into the
role of{sigma} 54 in L. plantarum and possibly other Gram-positive
bacteria in the control of expression of an important glucose transporter
that contributes to glucose-mediated catabolite control via modulation
of the PEP pool.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/3/695}
}
@ARTICLE{Stevens2008,
author = {Stevens, Tina and Krantz, Quentin T. and Linak, William P. and Hester,
Susan and Gilmour, M. Ian},
title = {Increased Transcription of Immune and Metabolic Pathways in Naive
and Allergic Mice Exposed to Diesel Exhaust},
journal = {Toxicol. Sci.},
year = {2008},
volume = {102},
pages = {359--370},
number = {2},
month = apr,
abstract = {Diesel exhaust (DE) has been shown to enhance allergic sensitization
in animals following high-dose instillation or chronic inhalation
exposure scenarios. The purpose of this study was to determine if
short-term exposures to diluted DE enhance allergic immune responses
to antigen, and identify possible mechanisms using microarray technology.
BALB/c mice were exposed to filtered air or diluted DE to yield particle
concentrations of 500 or 2000 {micro}g/m3 4 h/day on days 0-4. Mice
were immunized intranasally with ovalbumin (OVA) antigen or saline
on days 0-2, challenged on day 18 with OVA or saline, and all mice
were challenged with OVA on day 28. Mice were necropsied either 4
h after the last DE exposure on day 4, or 18, 48, and 96 h after
the last challenge. Immunological endpoints included OVA-specific
serum IgE, biochemical and cellular profiles of bronchoalveolar lavage
(BAL), and cytokine production in the BAL. OVA-immunized mice exposed
to both concentrations of DE had increased eosinophils, neutrophils,
lymphocytes, and interleukin-6 (high dose only) post-challenge compared
with OVA control, whereas DE/saline exposure yielded increases in
neutrophils at the high dose only. Transcriptional microarray analysis
4 h after the last DE exposure demonstrated distinct gene expression
profiles for the high-dose DE/OVA and DE/saline groups. DE/OVA induced
oxidative stress and metabolism pathways, whereas DE in the absence
of immunization modulated cell cycle control, growth and differentiation,
G-proteins, and cell adhesion pathways. This study shows for the
first time early changes in gene expression induced by the combination
of DE inhalation and mucosal immunization, which resulted in stronger
development of allergic eosinophilia.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/102/2/359}
}
@ARTICLE{Stewart2008,
author = {Stewart, Candace K. and Li, Julang and Golovan, Serguei P.},
title = {Adverse effects induced by short hairpin RNA expression in porcine
fetal fibroblasts},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {370},
pages = {113--117},
number = {1},
month = may,
abstract = {RNA interference is a recent, gene silencing technique that could
be extremely valuable in studying gene function, treating diseases,
and developing novel animal models for human diseases. Here, we investigated
the feasibility of applying shRNA-mediated RNA interference in fetal
fibroblasts for silencing of the myostatin gene and investigate adverse
effects of RNAi. We report that up to 97% silencing of myostatin
mRNA was achieved using shRNA constructs in transiently and stably
transfected fetal fibroblasts (p < 0.05). At the same time we also
demonstrate that high level of shRNA expression resulted in 10- to
1000-fold induction of interferon responsive genes (OAS1, IFN-[beta])
(p < 0.05). In addition we also report novel adverse effect of shRNA
expression in stably transfected cells--interference with microRNA
processing/transport which led to 500-fold increase in the level
of miR21 precursors (p < 0.05). Reduction of these side effects will
be essential to obtain long term stable RNAi silencing.},
issn = {0006-291X},
keywords = {RNA interference, shRNA, Myostatin, Interferon, MicroRNA},
url = {http://www.sciencedirect.com/science/article/B6WBK-4S3G8H5-1/2/33dfb66ba4a5aed45ae74310ab0cdad2}
}
@ARTICLE{Stickler2010,
author = {Stickler, P. and Visscher, G. De and Mesure, L. and Famaey, N. and
Martin, D. and Campbell, J.H. and Oosterwyck, H. Van and Meuris,
B. and Flameng, W.},
title = {Cyclically stretching developing tissue in vivo enhances mechanical
strength and organization of vascular grafts},
journal = {Acta Biomater},
year = {2010},
volume = {6},
pages = {2448--2456},
number = {7},
month = jul,
abstract = {Tissue-engineered vascular grafts must have qualities that rival native
vasculature, specifically the ability to remodel, the expression
of functional endothelial components and a dynamic and functional
extracellular matrix (ECM) that resists the forces of the arterial
circulation. We have developed a device that when inserted into the
peritoneal cavity, attracts cells around a tubular scaffold to generate
autologous arterial grafts. The device is capable of cyclically stretching
(by means of a pulsatile pump) developing tissue to increase the
mechanical strength of the graft. Pulsed (n=8) and unpulsed (n=8)
devices were implanted for 10days in Lovenaar sheep (n=8). Pulsation
occurred for a period of 5–8days before harvest. Thick unadhered
autologous tissue with cells residing in a collagen ECM was produced
in all devices. Collagen organization was greater in the circumferential
direction of pulsed tissue. Immunohistochemical labelling revealed
the hematopoietic origin of >90% cells and a significantly higher
coexpression with vimentin in pulsed tissue. F-actin expression,
mechanical failure strength and strain were also significantly increased
by pulsation. Moreover, tissue could be grafted as carotid artery
patches. This paper shows that unadhered tissue tubes with increased
mechanical strength and differentiation in response to pulsation
can be produced with every implant after a period of 10days. However,
these tissue tubes require a more fine-tuned exposure to pulsation
to be suitable for use as vascular grafts.},
issn = {1742-7061},
keywords = {Tissue engineering, Arterial grafts, Implantable bioreactor, Cyclic
stress},
publisher = {Elsevier,},
refid = {S1742-7061(10)00056-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1742706110000565?showall=true}
}
@ARTICLE{Stiening2008,
author = {Stiening, C.M. and Hoying, J.B. and Abdallah, M.B. and Hoying, A.M.
and Pandey, R. and Greer, K. and Collier, R.J.},
title = {The Effects of Endocrine and Mechanical Stimulation on Stage I Lactogenesis
in Bovine Mammary Epithelial Cells},
journal = {Journal of Dairy Science},
year = {2008},
volume = {91},
pages = {1053--1066},
number = {3},
month = mar,
abstract = {The study objective was to evaluate the effect of endocrine and mechanical
(gel release) signaling on bovine mammary epithelial cell ultrastructure
and gene expression. Cultures receiving only one stimulus demonstrated
partially differentiated ultrastructure, which included abundant
polysomes, limited rough endoplasmic reticulum, and absence of secretory
products, whereas the 2 stimuli together induced a more complete
lactogenic phenotype that included increased rough endoplasmic reticulum,
abundant lipid droplets, and secretory vesicles containing casein
micelles. The structural data indicated that although synthesis of
milk components was initiated, the copious synthesis and secretion
associated with stage II lactogenesis was not evident. Microarray
analysis revealed that both prolactin and gel release independently
regulated several genes linked to a wide array of cellular activities.
In combination, they regulated fewer genes targeted to lactogenesis.
Genes regulated by the combination treatment included claudin 7,
multiple caseins, xanthine oxidoreductase, and several protein synthesis,
packaging, and transport genes. Genes related to structural activity
including keratin 15 (morphogenesis), [alpha]-spectrin (cell shape
via actin cytoskeleton), and chitinase-like protein 1 (tissue remodeling)
were up-regulated by the combination treatment as was the transcription
factor Kruppel-like factor 2 (KLF-2). However, Snail 2, which down-regulates
and inhibits tight junction components, was repressed in response
to the combination treatment. These results suggest coordination
between endocrine and physical signals at the genomic level that
produces a more specific and targeted transcriptional response associated
with stage I lactogenesis. A molecular pathway analysis of the differentially
expressed genes revealed that genes regulating cell signaling were
linked to those regulating cell structure and adhesion.},
issn = {0022-0302},
keywords = {bovine, mammary, functional genomics, lactogenesis},
url = {http://www.sciencedirect.com/science/article/B9887-4YBKYSS-P/2/b4b035b14da49861be4a5e121aa677d3}
}
@ARTICLE{Stienstra2008,
author = {Stienstra, Rinke and Duval, Caroline and Keshtkar, Shohreh and van
der Laak, Jeroen and Kersten, Sander and Muller, Michael},
title = {Peroxisome Proliferator-activated Receptor {gamma} Activation Promotes
Infiltration of Alternatively Activated Macrophages into Adipose
Tissue},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {22620--22627},
number = {33},
month = aug,
abstract = {Obesity is associated with infiltration of macrophages into adipose
tissue. Adipose macrophages may contribute to an elevated inflammatory
status by secreting a variety of proinflammatory mediators, including
tumor necrosis factor {alpha} and interleukin-6 (IL-6). Recent data
suggest that during diet-induced obesity the phenotype of adipose-resident
macrophages changes from alternatively activated macrophages toward
a more classical and pro-inflammatory phenotype. Here, we explore
the effect of peroxisome proliferator-activated receptor {gamma}
activation on obesity-induced inflammation in 129SV mice fed a high
fat diet for 20 weeks. High fat feeding increased bodyweight gain,
adipose tissue mass, and liver triglycerides. Rosiglitazone treatment
further increased adipose mass, reduced liver triglycerides, and
changed adipose tissue morphology toward smaller adipocytes. Surprisingly,
rosiglitazone markedly increased the number of macrophages in adipose
tissue, as shown by immunohistochemical analysis and quantification
of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers
for classically activated macrophages including IL-18 were down-regulated,
whereas markers characteristic for alternatively activated macrophages
(arginase 1, IL-10) were up-regulated by rosiglitazone. Importantly,
conditioned media from rosiglitazone-treated alternatively activated
macrophages neutralized the inhibitory effect of macrophages on 3T3-L1
adipocyte differentiation, suggesting that alternatively activated
macrophages may be involved in mediating the effects of rosiglitazone
on adipose tissue morphology and mass. Our results suggest that short
term rosiglitazone treatment increases infiltration of alternatively
activated macrophages in adipose tissue. The alternatively activated
macrophages might play a role in peroxisome proliferator-activated
receptor{gamma}-dependent expansion and remodeling of adipose tissue.},
url = {http://www.jbc.org/cgi/content/abstract/283/33/22620}
}
@ARTICLE{Stienstra2007,
author = {Stienstra, Rinke and Mandard, Stephane and Patsouris, David and Maass,
Cathy and Kersten, Sander and Muller, Michael},
title = {Peroxisome Proliferator-Activated Receptor {alpha} Protects against
Obesity-Induced Hepatic Inflammation},
journal = {Endocrinology},
year = {2007},
volume = {148},
pages = {2753--2763},
number = {6},
month = jun,
abstract = {Recently it has become evident that obesity is associated with low-grade
chronic inflammation. The transcription factor peroxisome proliferator-activated
receptor {alpha} (PPAR{alpha}) has been shown to have a strong antiinflammatory
action in liver. However, the role of PPAR{alpha} in obesity-induced
inflammation is much less clear. Therefore, the aim of our study
was to determine whether PPAR{alpha} plays a role in obesity-induced
hepatic inflammation. To induce obesity, wild-type sv129 and PPAR{alpha}-/-
mice were exposed to a chronic high-fat diet (HFD), using a low-fat
diet (LFD) as control. In wild-type mice, HFD significantly increased
the hepatic and adipose expression of numerous genes involved in
inflammation. Importantly, this effect was amplified in PPAR{alpha}-/-
mice, suggesting an antiinflammatory role of PPAR{alpha} in liver
and adipose tissue. Further analysis identified specific chemokines
and macrophage markers, including monocyte chemotactic protein 1
and F4/80+, that were elevated in liver and adipose tissue of PPAR{alpha}-/-
mice, indicating increased inflammatory cell recruitment in the knockout
animals. When all groups of mice were analyzed together, a significant
correlation between hepatic triglycerides and expression of inflammatory
markers was observed. Many inflammatory genes that were up-regulated
in PPAR{alpha}-/- livers by HFD were down-regulated by treatment
with the PPAR{alpha} ligand Wy-14643 under normal nonsteatotic conditions,
either in vivo or in vitro, suggesting an antiinflammatory effect
of PPAR{alpha} that is independent of reduction in liver triglycerides.
In conclusion, our results suggest that PPAR{alpha} protects against
obesity-induced chronic inflammation in liver by reducing hepatic
steatosis, by direct down-regulation of inflammatory genes, and by
attenuating inflammation in adipose tissue.},
url = {http://endo.endojournals.org/cgi/content/abstract/148/6/2753}
}
@ARTICLE{Stienstra2007a,
author = {Stienstra, Rinke and Mandard, Stéphane and Tan, Nguan Soon and Wahli,
Walter and Trautwein, Christian and Richardson, Terrilyn A. and Lichtenauer-Kaligis,
Elgin and Kersten, Sander and Müller, Michael},
title = {The Interleukin-1 receptor antagonist is a direct target gene of
PPAR[alpha] in liver},
journal = {Journal of Hepatology},
year = {2007},
volume = {46},
pages = {869--877},
number = {5},
month = may,
abstract = {Background/Aims The Peroxisome Proliferator-Activated Receptor (PPAR)
[alpha] belongs to the superfamily of Nuclear Receptors and plays
an important role in numerous cellular processes, including lipid
metabolism. It is known that PPAR[alpha] also has an anti-inflammatory
effect, which is mainly achieved by down-regulating pro-inflammatory
genes. The objective of this study was to further characterize the
role of PPAR[alpha] in inflammatory gene regulation in liver.Results
According to Affymetrix micro-array analysis, the expression of various
inflammatory genes in liver was decreased by treatment of mice with
the synthetic PPAR[alpha] agonist Wy14643 in a PPAR[alpha]-dependent
manner. In contrast, expression of Interleukin-1 receptor antagonist
(IL-1ra), which was acutely stimulated by LPS treatment, was induced
by PPAR[alpha]. Up-regulation of IL-1ra by LPS was lower in PPAR[alpha]
-/- mice compared to Wt mice. Transactivation and chromatin immunoprecipitation
studies identified IL-1ra as a direct positive target gene of PPAR[alpha]
with a functional PPRE present in the promoter. Up-regulation of
IL-1ra by PPAR[alpha] was conserved in human HepG2 hepatoma cells
and the human monocyte/macrophage THP-1 cell line.Conclusions In
addition to down-regulating expression of pro-inflammatory genes,
PPAR[alpha] suppresses the inflammatory response by direct up-regulation
of genes with anti-inflammatory properties.},
issn = {0168-8278},
keywords = {PPAR, Liver, Inflammation, Microarray, Interleukin-1 receptor antagonist},
url = {http://www.sciencedirect.com/science/article/B6W7C-4MNHXG1-1/2/4bbc1499e0b1127e89eb13ee67973495}
}
@ARTICLE{Stimpson2009,
author = {Stimpson, Alexander J. and Pereira, Rhea S. and Kiss, John Z. and
Correll, Melanie J.},
title = {Extraction and labeling methods for microarrays using small amounts
of plant tissue},
journal = {Physiologia Plantarum},
year = {2009},
volume = {135},
pages = {229--236},
number = {3},
abstract = {Procedures were developed to maximize the yield of high-quality RNA
from small amounts of plant biomass for microarrays. Two disruption
techniques (bead milling and pestle and mortar) were compared for
the yield and the quality of RNA extracted from 1-week-old Arabidopsis
thaliana seedlings (approximately 0.5–30 mg total biomass). The
pestle and mortar method of extraction showed enhanced RNA quality
at the smaller biomass samples compared with the bead milling technique,
although the quality in the bead milling could be improved with additional
cooling steps. The RNA extracted from the pestle and mortar technique
was further tested to determine if the small quantity of RNA (500 ng–7 μg)
was appropriate for microarray analyses. A new method of low-quantity
RNA labeling for microarrays (NuGEN Technologies, Inc.) was used
on five 7-day-old seedlings (approximately 2.5Â mg fresh weight total)
of Arabidopsis that were grown in the dark and exposed to 1Â h of
red light or continued dark. Microarray analyses were performed on
a small plant sample (five seedlings; approximately 2.5Â mg) using
these methods and compared with extractions performed with larger
biomass samples (approximately 500 roots). Many well-known light-regulated
genes between the small plant samples and the larger biomass samples
overlapped in expression changes, and the relative expression levels
of selected genes were confirmed with quantitative real-time polymerase
chain reaction, suggesting that these methods can be used for plant
experiments where the biomass is extremely limited (i.e. spaceflight
studies).},
issn = {1399-3054},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-3054.2008.01191.x}
}
@ARTICLE{Stirewalt2008,
author = {Stirewalt, Derek L. and Meshinchi, Soheil and Kopecky, Kenneth J.
and Fan, Wenhong and Pogosova-Agadjanyan, Era L. and Engel, Julia
H. and Cronk, Michelle R. and Dorcy, Kathleen Shannon and McQuary,
Amy R. and Hockenbery, David and Wood, Brent and Heimfeld, Shelly
and Radich, Jerald P.},
title = {Identification of genes with abnormal expression changes in acute
myeloid leukemia},
journal = {Genes Chromosom. Cancer},
year = {2008},
volume = {47},
pages = {8--20},
number = {1},
abstract = {Abstract 10.1002/gcc.20500.abs Acute myeloid leukemia (AML) is one
of the most common and deadly forms of hematopoietic malignancies.
We hypothesized that microarray studies could identify previously
unrecognized expression changes that occur only in AML blasts. We
were particularly interested in those genes with increased expression
in AML, believing that these genes may be potential therapeutic targets.
To test this hypothesis, we compared gene expression profiles between
normal hematopoietic cells from 38 healthy donors and leukemic blasts
from 26 AML patients. Normal hematopoietic samples included CD34+
selected cells (N = 18), unselected bone marrows (N = 10), and unselected
peripheral bloods (N = 10). Twenty genes displayed AML-specific expression
changes that were not found in the normal hematopoietic cells. Subsequent
analyses using microarray data from 285 additional AML patients confirmed
expression changes for 13 of the 20 genes. Seven genes (BIK, CCNA1,
FUT4, IL3RA, HOMER3, JAG1, WT1) displayed increased expression in
AML, while 6 genes (ALDHA1A, PELO, PLXNC1, PRUNE, SERPINB9, TRIB2)
displayed decreased expression. Quantitative RT/PCR studies for the
7 over-expressed genes were performed in an independent set of 9
normal and 21 pediatric AML samples. All 7 over-expressed genes displayed
an increased expression in the AML samples compared to normals. Three
of the 7 over-expressed genes (WT1, CCNA1, and IL3RA) have already
been linked to leukemogenesis and/or AML prognosis, while little
is known about the role of the other 4 over-expressed genes in AML.
Future studies will determine their potential role in leukemogenesis
and their clinical significance. This article contains Supplementary
Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
© 2007 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20500}
}
@ARTICLE{Stirewalt2008a,
author = {Stirewalt, Derek L. and Mhyre, Andrew J. and Marcondes, Mario and
Pogosova-Agadjanyan, Era and Abbasi, Nissa and Radich, Jerald P.
and Deeg, H. Joachim},
title = {Tumour necrosis factor-induced gene expression in human marrow stroma:
clues to the pathophysiology of MDS?},
journal = {British Journal of Haematology},
year = {2008},
volume = {140},
pages = {444--453},
number = {4},
abstract = {Summary Aberrant regulation of the tumour necrosis factor alpha gene
(TNF) and stroma-derived signals are involved in the pathophysiology
of myelodysplasia. Therefore, KG1a, a myeloid leukaemia cell line,
was exposed to Tnf in the absence or presence of either HS-5 or HS-27a
cells, two human stroma cell lines. While KG1a cells were resistant
to Tnf-induced apoptosis in the absence of stroma cells, Tnf-promoted
apoptosis of KG1a cells in co-culture experiments with stroma cells.
To investigate the Tnf-induced signals from the stroma cells, we
examined expression changes in HS-5 and HS-27a cells after Tnf exposure.
DNA microarray studies found both discordant and concordant Tnf-induced
expression responses in the two stroma cell lines. Tnf promoted an
increased mRNA expression of pro-inflammatory cytokines [e.g. interleukin
(IL)6, IL8 and IL32]. At the same time, Tnf decreased the mRNA expression
of anti-apoptotic genes (e.g. BCL2L1) and increased the mRNA expression
of pro-apoptotic genes (e.g. BID). Overall, the results suggested
that Tnf induced a complex set of pro-inflammatory and pro-apoptotic
signals in stroma cells that promote apoptosis in malignant myeloid
clones. Additional studies will be required to determine which of
these signals are critical for the induction of apoptosis in the
malignant clones. Those insights, in turn, may point the way to novel
therapeutic approaches.},
issn = {1365-2141},
keywords = {stroma, tumour necrosis factor alpha gene, expression, myelodysplasia,
apoptosis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2007.06923.x}
}
@ARTICLE{Stirewalt2004,
author = {Stirewalt, Derek L and Pogosova-Agadjanyan, Era L and Khalid, Najma
and Hare, Dan R and Ladne, Paula A and Sala-Torra, Olga and Zhao,
Lue Ping and Radich, Jerald P},
title = {Single-stranded linear amplification protocol results in reproducible
and reliable microarray data from nanogram amounts of starting RNA},
journal = {Genomics},
year = {2004},
volume = {83},
pages = {321--331},
number = {2},
month = feb,
abstract = {The range of scientific questions utilizing DNA microarray techniques
is limited by the fact that these methods require 5-40 [mu]g of high-quality
total RNA. Thus, methods that reliably amplify the starting RNA amount
could expand the applicability of DNA microarray technology. We developed
a single-stranded linear amplification protocol (SLAP) that combines
the reproducibility of in vitro transcription and the amplification
robustness of polymerase chain reactions. We compared SLAP to the
NIH-IVT amplification protocol. SLAP displayed excellent conservation
of the 5'/3' signal and demonstrated the most robust amplification,
producing the recommended amounts of biotin-labeled RNA with as little
as 0.002 [mu]g of starting RNA. Both SLAP and NIH-IVT methods demonstrated
good reproducibility, but SLAP maintained the highest level of reliability
with RNA starting amounts of <0.05 [mu]g. These results suggest that
SLAP is an excellent alternative to IVT-based amplification protocols
when RNA is limited by small sample size.},
issn = {0888-7543},
keywords = {Microarray, In vitro transcription, Affymetrix, RNA amplification,
Eberwine, Array},
url = {http://www.sciencedirect.com/science/article/B6WG1-49JX80S-2/2/2dc9336b43f878daa63f875cd2339e0f}
}
@ARTICLE{Stock2007,
author = {Stock, Sarah J. and Kelly, Rodney W. and Riley, Simon C. and Calder,
Andrew A.},
title = {Natural antimicrobial production by the amnion},
journal = {American Journal of Obstetrics and Gynecology},
year = {2007},
volume = {196},
pages = {255.e1--255.e6},
number = {3},
month = mar,
abstract = {Objective The purpose of this study was to determine the expression
of natural antimicrobials in primary cultured amnion epithelial cells
and to examine their regulation by interleukin-1 beta (IL-1[beta]).Study
design Primary amnion epithelial cells were cultured from samples
that were obtained at prelabor cesarean section (n = 12) and stimulated
with IL-1[beta]. Natural antimicrobial messenger RNA expression was
determined by real-time quantitative polymerase chain reaction, and
protein was measured by enzyme-linked immunosorbent assay. Data was
analyzed by analysis of variance.Results Primary amnion epithelial
cells express messenger RNA for human beta defensin (HBD) 1 to 3,
secretory leukocyte protease inhibitor and elafin, but not HBD4.
IL-1[beta] 10 ng/mL stimulates HBD2 messenger RNA in a biphasic pattern,
with a 51-fold increase at 6 hours and a 67-fold at 12 hours (P <
.001). HBD2 protein production is significantly increased by 24 hours
(P < .05).Conclusion The amnion produces potent natural antimicrobials
that may help protect the pregnancy from infection. HBD2 production
is dramatically upregulated by the labor-associated inflammatory
cytokine IL-1[beta].},
issn = {0002-9378},
keywords = {amnion, defensin, infection, natural antimicrobial, pregnancy},
url = {http://www.sciencedirect.com/science/article/B6W9P-4N6FDG2-10/2/c64d4274da5087e8cfad21bf8fd1c5cc}
}
@ARTICLE{Stockel2008,
author = {Stockel, Jana and Welsh, Eric A. and Liberton, Michelle and Kunnvakkam,
Rangesh and Aurora, Rajeev and Pakrasi, Himadri B.},
title = {Global transcriptomic analysis of Cyanothece 51142 reveals robust
diurnal oscillation of central metabolic processes},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {6156--6161},
number = {16},
month = apr,
abstract = {Cyanobacteria are photosynthetic organisms and are the only prokaryotes
known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria
such as Cyanothece sp. ATCC 51142 produce oxygen and can also fix
atmospheric nitrogen, a process exquisitely sensitive to oxygen.
To accommodate such antagonistic processes, the intracellular environment
of Cyanothece oscillates between aerobic and anaerobic conditions
during a day-night cycle. This is accomplished by temporal separation
of the two processes: photosynthesis during the day and nitrogen
fixation at night. Although previous studies have examined periodic
changes in transcript levels for a limited number of genes in Cyanothece
and other unicellular diazotrophic cyanobacteria, a comprehensive
study of transcriptional activity in a nitrogen-fixing cyanobacterium
is necessary to understand the impact of the temporal separation
of photosynthesis and nitrogen fixation on global gene regulation
and cellular metabolism. We have examined the expression patterns
of nearly 5,000 genes in Cyanothece 51142 during two consecutive
diurnal periods. Our analysis showed that {approx}30% of these genes
exhibited robust oscillating expression profiles. Interestingly,
this set included genes for almost all central metabolic processes
in Cyanothece 51142. A transcriptional network of all genes with
significantly oscillating transcript levels revealed that the majority
of genes encoding enzymes in numerous individual biochemical pathways,
such as glycolysis, oxidative pentose phosphate pathway, and glycogen
metabolism, were coregulated and maximally expressed at distinct
phases during the diurnal cycle. These studies provide a comprehensive
picture of how a physiologically relevant diurnal light-dark cycle
influences the metabolism in a photosynthetic bacterium.},
url = {http://www.pnas.org/cgi/content/abstract/105/16/6156}
}
@ARTICLE{Stocker2006,
author = {Stocker, Gisela and Vandevyver, Caroline and Hilbrig, Frank and Freitag,
Ruth},
title = {Purification of RT-PCR Competent Poly(A) mRNA from Crude Cell Lysate
by Affinity Precipitation},
journal = {Biotechnol Progress},
year = {2006},
volume = {22},
pages = {1621--1629},
number = {6},
abstract = {Abstract 10.1002/btpr.60095.abs Stimuli-responsive bioconjugates consisting
of avidin covalently linked to poly(N-isopropylacrylamide) were used
for the recovery of poly(A) mRNA hybridized to biotinylated poly(dT)-tags
from crude cell lysates (Jurkat cells) by affinity precipitation.
The bioconjugates are soluble in cold water but precipitate readily
once a critical solution temperature (33 °C in pure water) is surpassed.
The process is fully reversible and shows the expected dependencies
on the composition of the aqueous solution and the bioconjugate chemistry.
The results of the affinity precipitation were compared to those
achieved with an accepted standard purification of poly(A) mRNA using
avidin-activated magnetic beads. Both yield and quality/purity of
the affinity precipitated poly(A) mRNA were found to be similar or
better (especially removal of rRNA) than for poly(A) mRNA prepared
by the magnetic particle-based protocol, while both mRNA isolates
performed equally well in standard reverse transcriptase amplification
(RT-PCR) of a β actin transcript fragment. Poly(A) mRNA purification
schemes based on affinity precipitation require no dedicated equipment
and should have advantages in terms of scalability, handling, and
costs.},
issn = {1520-6033},
publisher = {American Chemical Society},
url = {http://dx.doi.org/10.1021/bp060095u}
}
@ARTICLE{Stockhammer2010,
author = {Stockhammer, Oliver W. and Rauwerda, Han and Wittink, Floyd R. and
Breit, Timo M. and Meijer, Annemarie H. and Spaink, Herman P.},
title = {Transcriptome analysis of Traf6 function in the innate immune response
of zebrafish embryos},
journal = {Molecular Immunology},
year = {2010},
volume = {48},
pages = {179--190},
number = {1-3},
month = nov,
abstract = {TRAF6 is a key player at the cross-roads of development and immunity.
The analysis of its in vivo molecular function is a great challenge
since severe developmental defects and early lethality caused by
Traf6 deficiency in knock-out mice interfere with analyses of the
immune response. In this study we have used a new strategy to analyze
the function of Traf6 in a zebrafish-Salmonella infectious disease
model. In our approach the effect of a Traf6 translation-blocking
morpholino was titrated down to avoid developmental defects and the
response to infection under these conditions was studied using the
combination of microarray analysis and whole transcriptome deep sequencing.
Transcriptome profiling of the traf6 knock-down allowed the identification
of a gene set whose responsiveness during infection is highly dependent
on Traf6. Expression trend analysis based on the resulting datasets
identified nine clusters of genes with characteristic transcription
response profiles, demonstrating Traf6 has a dynamic role as a positive
and negative regulator. Among the Traf6-dependent genes was a large
set of well known anti-microbial and inflammatory genes. Additionally,
we identified several genes which were not previously linked to a
response to microbial infection, such as the fertility hormone gene
gnrh2 and the DNA-damage regulated autophagy modulator 1 gene dram1.
With the use of the zebrafish embryo model we have now analyzed the
in vivo function of Traf6 in the innate immune response without interference
of adaptive immunity.},
issn = {0161-5890},
keywords = {Bacterial infection, Gene regulation, Signal transduction, Toll-like
receptors, RNAseq, Microarray},
url = {http://www.sciencedirect.com/science/article/pii/S0161589010005559}
}
@ARTICLE{Stockhammer2009,
author = {Stockhammer, Oliver W. and Zakrzewska, Anna and Hegedus, Zoltan and
Spaink, Herman P. and Meijer, Annemarie H.},
title = {Transcriptome Profiling and Functional Analyses of the Zebrafish
Embryonic Innate Immune Response to Salmonella Infection},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {5641--5653},
number = {9},
month = may,
abstract = {Due to the clear separation of innate immunity from adaptive responses,
the externally developing zebrafish embryo represents a useful in
vivo model for identification of innate host determinants of the
response to bacterial infection. Here we performed a time-course
transcriptome profiling study and gene ontology analysis of the embryonic
innate immune response to infection with two model Salmonella strains
that elicit either a lethal infection or an attenuated response.
The transcriptional response to infection with both the lethal strain
and the avirulent LPS O-Ag mutant strain showed clear conservation
with host responses detected in other vertebrate models and human
cells, including induction of genes encoding cell surface receptors,
signaling intermediates, transcription factors, and inflammatory
mediators. Furthermore, our study led to the identification of a
large set of novel immune response genes and infection markers, the
future functional characterization of which will support vertebrate
genome annotation. From the time series and bacterial strain comparisons,
matrix metalloproteinase genes, including mmp9, were among the most
consistent infection-responsive genes. Purified Salmonella flagellin
also strongly induced mmp9 expression. Using knockdown analysis,
we showed that this gene was downstream of the zebrafish homologs
of the flagellin receptor TLR5 and the adaptor MyD88. Additionally,
flagellin-mediated induction of other inflammation markers, including
il1b, il8, and cxcl-C1c, was reduced upon Tlr5 knockdown as well
as expression of irak3, a putative negative TLR pathway regulator.
Finally, we showed that induction of il1b, mmp9, and irak3 requires
Myd88-dependent signaling, while ifn1 and il8 were induced Myd88
independently during Salmonella infection.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/9/5641}
}
@ARTICLE{Stoebner2008,
author = {Stoebner, Pierre E. and Le Gallic, Lionel and Berthe, Marie L. and
Boulle, Nathalie and Lallemant, Benjamin and Marque, Myriam and Gaspard,
Catherine and Delfour, Christophe and Lavabre-Bertrand, Thierry and
Martinez, Jean and Meunier, Laurent},
title = {Decreased expression of thymidine phosphorylase/platelet-derived
endothelial cell growth factor in basal cell carcinomas},
journal = {Experimental Dermatology},
year = {2008},
volume = {17},
pages = {908--915},
number = {11},
abstract = {Abstract:  Thymidine phosphorylase (TP)/platelet-derived endothelial
cell growth factor is associated with tumor angiogenesis. We evaluated
the TP mRNA and protein expression in basal cell carcinomas (BCC)
and in various skin tumors including numerous BCC histological simulants.
Immunohistochemistry was performed on 99 paraffin sections of formalin-fixed
skin tumors using monoclonal antibodies (mAb) against TP. TP mRNA
levels were measured by real time RT-PCR in whole BCCs (wBCC) and
laser capture microdissected (LCM) BCC tumor cells. TP immunostaining
was negative in all BCC variants and in most of the benign trichogeneic
tumors studied. By contrast, TP was constantly immunodetected in
actinic keratosis (AK), squamous cell carcinomas (SCC), syringomatous
carcinomas (SC), basosquamous carcinomas (BSC) and melanomas. TP
mRNA levels were low and statistically not different in wBCC and
normal skin but were strongly downregulated in LCM-BCC as compared
with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an
useful marker to differentiate BCC from AK, SCC, BSC and SC but not
from trichoblastic tumors, (ii) the lack of TP protein expression
in BCC tumoral cells is linked to transcriptional regulatory mechanisms,
(iii) the low TP mRNA levels in whole BCC may be related to the low
intra-tumoral microvessel density, the slow growth and the very low
metastatic potential of these tumors.},
issn = {1600-0625},
keywords = {angiogenesis, basal cell carcinoma, immunohistochemistry, platelet-derived
endothelial cell growth factor, thymidine phosphorylase},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0625.2008.00718.x}
}
@ARTICLE{STOECK2010,
author = {STOECK, THORSTEN and BASS, DAVID and NEBEL, MARKUS and CHRISTEN,
RICHARD and JONES, MEREDITH D. M. and BREINER, HANS-WERNER and RICHARDS,
THOMAS A.},
title = {Multiple marker parallel tag environmental DNA sequencing reveals
a highly complex eukaryotic community in marine anoxic water},
journal = {Molecular Ecology},
year = {2010},
volume = {19},
pages = {21--31},
abstract = {Abstract Sequencing of ribosomal DNA clone libraries amplified from
environmental DNA has revolutionized our understanding of microbial
eukaryote diversity and ecology. The results of these analyses have
shown that protist groups are far more genetically heterogeneous
than their morphological diversity suggests. However, the clone library
approach is labour-intensive, relatively expensive, and methodologically
biased. Therefore, even the most intensive rDNA library analyses
have recovered only small samples of much larger assemblages, indicating
that global environments harbour a vast array of unexplored biodiversity.
High-throughput parallel tag 454 sequencing offers an unprecedented
scale of sampling for molecular detection of microbial diversity.
Here, we report a 454 protocol for sampling and characterizing assemblages
of eukaryote microbes. We use this approach to sequence two SSU rDNA
diversity markers—the variable V4 and V9 regions—from 10 L of
anoxic Norwegian fjord water. We identified 38Â 116Â V4 and 15Â 156Â V9
unique sequences. Both markers detect a wide range of taxonomic groups
but in both cases the diversity detected was dominated by dinoflagellates
and close relatives. Long-tailed rank abundance curves suggest that
the 454 sequencing approach provides improved access to rare genotypes.
Most tags detected represent genotypes not currently in GenBank,
although many are similar to database sequences. We suggest that
current understanding of the ecological complexity of protist communities,
genetic diversity, and global species richness are severely limited
by the sequence data hitherto available, and we discuss the biological
significance of this high amplicon diversity.},
issn = {1365-294X},
keywords = {marine anoxic, microbial eukaryotes, 454 sequencing, V4 SSU rDNA,
V9 SSU rDNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2009.04480.x}
}
@ARTICLE{Stoeck2009,
author = {Stoeck, Thorsten and Behnke, Anke and Christen, Richard and Amaral-Zettler,
Linda and Rodriguez-Mora, Maria and Chistoserdov, Andrei and Orsi,
William and Edgcomb, Virginia},
title = {Massively parallel tag sequencing reveals the complexity of anaerobic
marine protistan communities},
journal = {BMC Biology},
year = {2009},
volume = {7},
pages = {72},
number = {1},
abstract = {BACKGROUND:Recent advances in sequencing strategies make possible
unprecedented depth and scale of sampling for molecular detection
of microbial diversity. Two major paradigm-shifting discoveries include
the detection of bacterial diversity that is one to two orders of
magnitude greater than previous estimates, and the discovery of an
exciting 'rare biosphere' of molecular signatures ('species') of
poorly understood ecological significance. We applied a high-throughput
parallel tag sequencing (454 sequencing) protocol adopted for eukaryotes
to investigate protistan community complexity in two contrasting
anoxic marine ecosystems (Framvaren Fjord, Norway; Cariaco deep-sea
basin, Venezuela). Both sampling sites have previously been scrutinized
for protistan diversity by traditional clone library construction
and Sanger sequencing. By comparing these clone library data with
454 amplicon library data, we assess the efficiency of high-throughput
tag sequencing strategies. We here present a novel, highly conservative
bioinformatic analysis pipeline for the processing of large tag sequence
data sets.RESULTS:The analyses of ca. 250,000 sequence reads revealed
that the number of detected Operational Taxonomic Units (OTUs) far
exceeded previous richness estimates from the same sites based on
clone libraries and Sanger sequencing. More than 90% of this diversity
was represented by OTUs with less than 10 sequence tags. We detected
a substantial number of taxonomic groups like Apusozoa, Chrysomerophytes,
Centroheliozoa, Eustigmatophytes, hyphochytriomycetes, Ichthyosporea,
Oikomonads, Phaeothamniophytes, and rhodophytes which remained undetected
by previous clone library-based diversity surveys of the sampling
sites. The most important innovations in our newly developed bioinformatics
pipeline employ (i) BLASTN with query parameters adjusted for highly
variable domains and a complete database of public ribosomal RNA
(rRNA) gene sequences for taxonomic assignments of tags; (ii) a clustering
of tags at k differences (Levenshtein distance) with a newly developed
algorithm enabling very fast OTU clustering for large tag sequence
data sets; and (iii) a novel parsing procedure to combine the data
from individual analyses.CONCLUSION:Our data highlight the magnitude
of the under-sampled 'protistan gap' in the eukaryotic tree of life.
This study illustrates that our current understanding of the ecological
complexity of protist communities, and of the global species richness
and genome diversity of protists, is severely limited. Even though
454 pyrosequencing is not a panacea, it allows for more comprehensive
insights into the diversity of protistan communities, and combined
with appropriate statistical tools, enables improved ecological interpretations
of the data and projections of global diversity.},
doi = {10.1186/1741-7007-7-72},
issn = {1741-7007},
pubmedid = {19886985},
url = {http://www.biomedcentral.com/1741-7007/7/72}
}
@ARTICLE{Stoecker2009,
author = {Stoecker, Katharina and Weigelt, Karin and Ebert, Stefanie and Karlstetter,
Marcus and Walczak, Yana and Langmann, Thomas},
title = {Induction of STAP-1 promotes neurotoxic activation of microglia},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {379},
pages = {121--126},
number = {1},
month = jan,
abstract = {Activated microglia contribute to neurodegenerative processes in the
brain and the retina. Via DNA-microarray analysis, we have previously
identified up-regulation of several immune-related genes in the dystrophic
retina of retinoschisin-deficient (Rs1h-/Y) mice. Here we report
a strong overexpression of transcripts for the signal-transducing
adaptor protein-1 (STAP-1) in isolated Rs1h-/Y microglia. Furthermore,
STAP-1 expression was induced in activated bone marrow-derived macrophages
as well as LPS-, interferon-[gamma]-, and CpG-stimulated myeloid
cell lines. Ectopic expression of STAP-1 in BV-2 microglia changed
the morphology and cytoskeletal organization of the cells and transformed
ramified cells to an activated state. STAP-1 overexpression also
leads to an interaction with the M-CSF receptor/c-Fms diminishing
its ligand-dependent phosphorylation. Finally, STAP-1 expressing
cells showed strongly reduced migration with increased cytotoxicity
against 661W photoreceptor like cells. Taken together, our study
implicates a previously unknown role of STAP-1 in pro-inflammatory
microglia activation potentially contributing to neuronal apoptosis
and degeneration.},
issn = {0006-291X},
keywords = {Microglia, Adaptor protein, Migration, Phagocytosis, c-Fms, NO secretion,
Photoreceptors, Neurotoxicity, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6WBK-4V5N7M2-2/2/d4beffb15c4b37538ea04f6dbb21bf1c}
}
@ARTICLE{Stoecklin2008,
author = {Stoecklin, Georg and Tenenbaum, Scott A. and Mayo, Thomas and Chittur,
Sridar V. and George, Ajish D. and Baroni, Timothy E. and Blackshear,
Perry J. and Anderson, Paul},
title = {Genome-wide Analysis Identifies Interleukin-10 mRNA as Target of
Tristetraprolin},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {11689--11699},
number = {17},
month = apr,
abstract = {Tristetraprolin (TTP) is an RNA-binding protein required for the rapid
degradation of mRNAs containing AU-rich elements. Targets regulated
by TTP include the mRNAs encoding tumor necrosis factor-{alpha},
granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2),
and immediate early response 3. To identify novel target mRNAs of
TTP in macrophages, we used a genome-wide approach that combines
RNA immunoprecipitation and microarray analysis. A list was compiled
of 137 mRNAs that are associated with TTP with an estimated accuracy
on the order of 90%. Sequence analysis revealed a highly significant
enrichment of AU-rich element motifs, with AUUUA pentamers present
in 96% and UUAUUUAUU nonamers present in 44% of TTP-associated mRNAs.
We further show that IL-10 is a novel target regulated by TTP. IL-10
mRNA levels were found to be elevated because of a reduced decay
rate in primary macrophages from TTP-/- mice. Our study demonstrates
the importance of experimental approaches for identifying targets
of RNA-binding proteins.},
url = {http://www.jbc.org/cgi/content/abstract/283/17/11689}
}
@ARTICLE{Stohl2005,
author = {Stohl, Elizabeth A. and Criss, Alison K. and Seifert, H. Steven},
title = {The transcriptome response of Neisseria gonorrhoeae to hydrogen peroxide
reveals genes with previously uncharacterized roles in oxidative
damage protection},
journal = {Molecular Microbiology},
year = {2005},
volume = {58},
pages = {520--532},
number = {2},
abstract = {Summary Symptomatic gonococcal infection, caused by the pathogen Neisseria
gonorrhoeae (Gc), is characterized by the influx of polymorphonuclear
leukocytes (PMNs) to the site of infection. Although PMNs possess
several mechanisms of oxidative killing, intact Gc can be found associated
with PMNs, suggesting that gonococcal defences against oxidative
stress are crucial for its ability to evade killing by PMNs. We used
microarrays to identify genes that were differentially expressed
after transient exposure of Gc to hydrogen peroxide (H2O2). Of the
75 genes found to be upregulated after H2O2 treatment, over one-quarter,
including two of the most highly upregulated genes (NGO1686 and NGO554),
were predicted to encode proteins with unknown functions. Further
characterization of a subset of these upregulated genes demonstrated
that NGO1686, a putative zinc metalloprotease, protects against oxidative
damage caused by both H2O2 and cumene hydroperoxide, and that NGO554,
a Gc-specific protein, acts to protect against damage caused by high
levels of H2O2. Our current study also ascribes a role in H2O2 damage
protection to recN, a gene previously characterized for its role
in DNA repair. A PMN survival assay demonstrated that the recN and
NGO1686 mutants were more susceptible to killing than the parent
strain FA1090. These results define for the first time the robust
transcriptional response to H2O2 by this strict human pathogen and
underscore the importance of this system for survival to host defences.},
issn = {1365-2958},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2005.04839.x}
}
@ARTICLE{Stoiber2010,
author = {Stoiber, Tasha L. and Shafer, Martin M. and Armstrong, David E.},
title = {Differential effects of copper and cadmium exposure on toxicity endpoints
and gene expression in Chlamydomonas reinhardtii},
journal = {Environmental Toxicology and Chemistry},
year = {2010},
volume = {29},
pages = {191--200},
number = {1},
abstract = {Abstract 10.1002/etc.6.abs The toxicity of cadmium to aquatic organisms
is well known, but the mechanisms of toxicity are not as clearly
understood. In the present study, Cd bioassay experiments incorporating
both traditional endpoints and novel thiol-based endpoints were conducted
with Chlamydomonas reinhardtii. The results were compared with results
from previous bioassay experiments to probe the apparent contrasting
biochemical mechanisms of toxicity of copper and cadmium as expressed
in cellular glutathione and the glutathione cycle. Total glutathione
and reduced to oxidized glutathione ratio (GSH/GSSG) measurements
were remarkably different in Cd- compared with Cu-exposed cells.
Whereas total glutathione in cells decreased with increasing Cu concentration,
Cd caused dramatic increases. Total glutathione increased by 4.5-fold
with 80 nM Cd treatment over concentrations in Cd-free controls.
Glutathione reductase (GR) enzyme activity was positively correlated
(r2Cu = 0.96, r2Cd = 0.85) with glutathione concentrations
for both metals. Measurements of mRNA for GR were increased 2-fold
in response to Cd exposure (80 nM) and correlated well with GR enzyme
activity. Glutathione concentrations and GR enzyme activity are useful
endpoints for both Cu and Cd toxicity in algae, even though the metals
elicit opposing responses. We conclude that Cu decreases glutathione
concentrations by inhibiting GR enzyme activity. In contrast, Cd
stimulates GR enzyme activity and increases glutathione concentrations
as cells respond to Cd-induced stress by producing increased antioxidant
capacity. The present study demonstrates that determining the glutathione
response in cells is important for understanding the metal-specific
mechanisms of toxicity and that these associated novel endpoints
may be useful metrics for accurately predicting toxicity. Environ.
Toxicol. Chem. 2010;29:191–200. © 2009 SETAC},
issn = {1552-8618},
keywords = {Glutathione, Cadmium, Chlamydomonas reinhardtii, Trace metals},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/etc.6}
}
@ARTICLE{Stolc2005,
author = {Stolc, Viktor and Samanta, Manoj Pratim and Tongprasit, Waraporn
and Marshall, Wallace F.},
title = {Genome-wide transcriptional analysis of flagellar regeneration in
Chlamydomonas reinhardtii identifies orthologs of ciliary disease
genes},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {3703--3707},
number = {10},
month = mar,
abstract = {The important role that cilia and flagella play in human disease creates
an urgent need to identify genes involved in ciliary assembly and
function. The strong and specific induction of flagellar-coding genes
during flagellar regeneration in Chlamydomonas reinhardtii suggests
that transcriptional profiling of such cells would reveal new flagella-related
genes. We have conducted a genome-wide analysis of RNA transcript
levels during flagellar regeneration in Chlamydomonas by using maskless
photolithography method-produced DNA oligonucleotide microarrays
with unique probe sequences for all exons of the 19,803 predicted
genes. This analysis represents previously uncharacterized whole-genome
transcriptional activity profiling study in this important model
organism. Analysis of strongly induced genes reveals a large set
of known flagellar components and also identifies a number of important
disease-related proteins as being involved with cilia and flagella,
including the zebrafish polycystic kidney genes Qilin, Reptin, and
Pontin, as well as the testis-expressed tubby-like protein TULP2.},
url = {http://www.pnas.org/cgi/content/abstract/102/10/3703}
}
@ARTICLE{Stolc2005a,
author = {Stolc, Viktor and Samanta, Manoj Pratim and Tongprasit, Waraporn
and Sethi, Himanshu and Liang, Shoudan and Nelson, David C. and Hegeman,
Adrian and Nelson, Clark and Rancour, David and Bednarek, Sebastian
and Ulrich, Eldon L. and Zhao, Qin and Wrobel, Russell L. and Newman,
Craig S. and Fox, Brian G. and Phillips, George N., Jr. and Markley,
John L. and Sussman, Michael R.},
title = {Identification of transcribed sequences in Arabidopsis thaliana by
using high-resolution genome tiling arrays},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {4453--4458},
number = {12},
month = mar,
abstract = {Using a maskless photolithography method, we produced DNA oligonucleotide
microarrays with probe sequences tiled throughout the genome of the
plant Arabidopsis thaliana. RNA expression was determined for the
complete nuclear, mitochondrial, and chloroplast genomes by tiling
5 million 36-mer probes. These probes were hybridized to labeled
mRNA isolated from liquid grown T87 cells, an undifferentiated Arabidopsis
cell culture line. Transcripts were detected from at least 60% of
the nearly 26,330 annotated genes, which included 151 predicted genes
that were not identified previously by a similar genome-wide hybridization
study on four different cell lines. In comparison with previously
published results with 25-mer tiling arrays produced by chromium
masking-based photolithography technique, 36-mer oligonucleotide
probes were found to be more useful in identifying intron-exon boundaries.
Using two-dimensional HPLC tandem mass spectrometry, a small-scale
proteomic analysis was performed with the same cells. A large amount
of strongly hybridizing RNA was found in regions "antisense" to known
genes. Similarity of antisense activities between the 25-mer and
36-mer data sets suggests that it is a reproducible and inherent
property of the experiments. Transcription activities were also detected
for many of the intergenic regions and the small RNAs, including
tRNA, small nuclear RNA, small nucleolar RNA, and microRNA. Expression
of tRNAs correlates with genome-wide amino acid usage.},
url = {http://www.pnas.org/cgi/content/abstract/102/12/4453}
}
@ARTICLE{Stolhaug2006,
author = {Stolhaug, Anne and Bergh, Kare},
title = {Identification and Differentiation of Legionella pneumophila and
Legionella spp. with Real-Time PCR Targeting the 16S rRNA Gene and
Species Identification by mip Sequencing},
journal = {Appl. Envir. Microbiol.},
year = {2006},
volume = {72},
pages = {6394--6398},
number = {9},
month = sep,
abstract = {Fluorescent resonance energy transfer probes targeting the 16S rRNA
gene were constructed for a sensitive and specific real-time PCR
for identification and differentiation of Legionella pneumophila
from other Legionella spp. For identification of non-L. pneumophila
spp. by direct amplicon sequencing, two conventional PCR assays targeting
the mip gene were established.},
url = {http://aem.asm.org/cgi/content/abstract/72/9/6394}
}
@ARTICLE{Stoltz2010,
author = {Stoltz, David A. and Meyerholz, David K. and Pezzulo, Alejandro A.
and Ramachandran, Shyam and Rogan, Mark P. and Davis, Greg J. and
Hanfland, Robert A. and Wohlford-Lenane, Chris and Dohrn, Cassie
L. and Bartlett, Jennifer A. and Nelson, George A., IV and Chang,
Eugene H. and Taft, Peter J. and Ludwig, Paula S. and Estin, Mira
and Hornick, Emma E. and Launspach, Janice L. and Samuel, Melissa
and Rokhlina, Tatiana and Karp, Philip H. and Ostedgaard, Lynda S.
and Uc, Aliye and Starner, Timothy D. and Horswill, Alexander R.
and Brogden, Kim A. and Prather, Randall S. and Richter, Sandra S.
and Shilyansky, Joel and McCray, Paul B., Jr. and Zabner, Joseph
and Welsh, Michael J.},
title = {Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial
Eradication at Birth},
journal = {Science Translational Medicine},
year = {2010},
volume = {2},
pages = {29ra31--},
number = {29},
month = apr,
abstract = {Lung disease causes most of the morbidity and mortality in cystic
fibrosis (CF). Understanding the pathogenesis of this disease has
been hindered, however, by the lack of an animal model with characteristic
features of CF. To overcome this problem, we recently generated pigs
with mutated CFTR genes. We now report that, within months of birth,
CF pigs spontaneously developed hallmark features of CF lung disease,
including airway inflammation, remodeling, mucus accumulation, and
infection. Their lungs contained multiple bacterial species, suggesting
that the lungs of CF pigs have a host defense defect against a wide
spectrum of bacteria. In humans, the temporal and causal relations
between inflammation and infection have remained uncertain. To investigate
these processes, we studied newborn pigs. Their lungs showed no inflammation
but were less often sterile than controls. Moreover, after introduction
of bacteria into their lungs, pigs with CF failed to eradicate bacteria
as effectively as wild-type pigs. These results suggest that impaired
bacterial elimination is the pathogenic event that initiates a cascade
of inflammation and pathology in CF lungs. Our finding that pigs
with CF have a host defense defect against bacteria within hours
of birth provides an opportunity to further investigate CF pathogenesis
and to test therapeutic and preventive strategies that could be deployed
before secondary consequences develop.},
url = {http://stm.sciencemag.org/cgi/content/abstract/2/29/29ra31}
}
@ARTICLE{Stommel2009,
author = {Stommel, John R. and Lightbourn, Gordon J. and Winkel, Brenda S.
and Griesbach, Robert J.},
title = {Transcription Factor Families Regulate the Anthocyanin Biosynthetic
Pathway in Capsicum annuum},
journal = {J. Amer. Soc. Hort. Sci.},
year = {2009},
volume = {134},
pages = {244--251},
number = {2},
month = mar,
abstract = {Anthocyanin structural gene transcription requires the expression
of at least one member of each of three transcription factor families:
MYC, MYB, and WD40. These transcription factors form a complex that
binds to structural gene promoters, thereby modulating gene expression.
Capsicum annuum L. (pepper) displays a wide spectrum of tissue-specific
anthocyanin pigmentation, making it a useful model for the study
of anthocyanin accumulation. To determine the genetic basis for tissue-specific
pigmentation, we used real-time polymerase chain reaction to evaluate
the expression of anthocyanin biosynthetic (Chs, Dfr, and Ans) and
regulatory (Myc, MybA, and Wd) genes in flower, fruit, and foliar
tissue from pigmented and nonpigmented C. annuum genotypes. No differences
were observed in expression of the Wd gene among these tissues. However,
in all cases, biosynthetic gene transcript levels were significantly
higher in anthocyanin-pigmented tissue than in nonpigmented tissues.
MybA and Myc transcript levels were also substantially higher in
anthocyanin-pigmented floral and fruit tissues. Our results demonstrate
that differential expression of C. annuum MybA as well as Myc occurs
coincident with anthocyanin accumulation in C. annuum flower and
fruit tissues. In contrast to the situation in flowers and fruit,
differential expression of MybA and Myc was not observed in foliar
tissue, suggesting that different mechanisms contribute to the regulation
of anthocyanin biosynthesis in different parts of the C. annuum plant.
Cloning and sequencing of MybA genomic and cDNA clones revealed two
introns of 249 and 441 bp between the R2R3 domains. Whereas the Myb
R2R3 domains were conserved between C. annuum and Petunia xhybrida
Vilm., the sequence of the non-R2R3 domains was not conserved, with
very little homology in these related Solanaceous species.},
url = {http://journal.ashspublications.org/cgi/content/abstract/134/2/244}
}
@ARTICLE{Stone2007,
author = {Stone, Austin V. and Ma, Jianjun and Whitlock, Patrick W. and Koman,
L. Andrew and Smith, Thomas L. and Smith, Beth P. and Callahan, Michael
F.},
title = {Effects of Botox® and Neuronox® on muscle force generation in mice},
journal = {J. Orthop. Res.},
year = {2007},
volume = {25},
pages = {1658--1664},
number = {12},
abstract = {Abstract 10.1002/jor.20450.abs The current study determined the dose–response
relationship for inhibition of muscle force of two commercially available
botulinum neurotoxin type-A (BoNTA) preparations (Botox® and Neuronox®)
in a murine model and characterized the time course of recovery from
the toxin-induced muscle paralysis. The effect of freezing reconstituted
toxin on toxin potency was also determined. The gastrocnemius muscles
in male CD-1 mice were injected with either saline or BoNTA (0.3–3.0
U/kg), and muscle force generation was examined following stimulation
of the tibial nerve (single twitch and 15–200 Hz tetany). Botox
and Neuronox produced nearly equivalent decrements in muscle force
(30%–90%) at 4 days after toxin injection. At 28 days after injection
(1 U/kg), muscle force had recovered from the effects of both toxin
preparations. Maintaining reconstituted toxin at −80°C for up
to 5 months did not result in significant loss of toxin activity.
The results of this study suggest that Botox and Neuronox produce
equivalent responses in a murine model, and, in contrast to other
models, muscle recovery is rapid with doses of toxin that produce
less than maximal decrements in muscle force. © 2007 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
25:1658–1664, 2007},
issn = {1554-527X},
keywords = {botulinum toxin, botulinum neurotoxin A, dose, muscle recovery, mouse},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jor.20450}
}
@ARTICLE{Stone2011,
author = {Stone, Richard A. and McGlinn, Alice M. and Baldwin, Donald A. and
Tobias, John W. and Iuvone, P. Michael and Khurana, Tejvir S.},
title = {Image Defocus and Altered Retinal Gene Expression in Chick: Clues
to the Pathogenesis of Ametropia},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {5765-5777},
number = {8},
abstract = {Purpose.Because of the retina's role in refractive development, this
study was conducted to analyze the retinal transcriptome in chicks
wearing a spectacle lens, a well-established means of inducing refractive
errors, to identify gene expression alterations and to develop novel
mechanistic hypotheses about refractive development. Methods.One-week-old
white Leghorn chicks wore a unilateral spectacle lens of +15 or -15
D for 6 hours or 3 days. With total RNA from the retina/(retinal
pigment epithelium, RPE), chicken gene microarrays were used to compare
gene expression levels between lens-wearing and contralateral control
eyes (n = 6 chicks for each condition). Normalized microarray signal
intensities were evaluated by analysis of variance, using a false
discovery rate of <10% as the statistical criterion. Selected differentially
expressed genes were validated by qPCR. Results.Very few retina/RPE
transcripts were differentially expressed after plus lens wear. In
contrast, approximately 1300 transcripts were differentially expressed
under each of the minus lens conditions, with minimal overlap. For
each condition, low fold-changes typified the altered transcriptome.
Differentially regulated genes under the minus lens conditions included
many potentially informative signaling molecules and genes whose
protein products have roles in intrinsic retinal circadian rhythms.
Conclusions.Plus or minus lens wear induce markedly different, not
opposite, alterations in retina/RPE gene expression. The initial
retinal responses to defocus are quite different from those when
the eye growth patterns are well established, suggesting that different
mechanisms govern the initiation and persistence or progression of
refractive errors. The gene lists identify promising signaling candidates
and regulatory pathways for future study, including a potential role
for circadian rhythms in refractive development.},
doi = {10.1167/iovs.10-6727},
eprint = {http://www.iovs.org/cgi/reprint/52/8/5765.pdf},
url = {http://www.iovs.org/cgi/content/abstract/52/8/5765}
}
@ARTICLE{Stoodley2011,
author = {Stoodley, Paul and Conti, Stephen F. and DeMeo, Patrick J. and Nistico,
Laura and Melton-Kreft, Rachael and Johnson, Sandra and Darabi, Ali
and Ehrlich, Garth D. and Costerton, J. William and Kathju, Sandeep},
title = {Characterization of a mixed MRSA/MRSE biofilm in an explanted total
ankle arthroplasty},
journal = {FEMS Immunology \& Medical Microbiology},
year = {2011},
volume = {62},
pages = {66--74},
number = {1},
abstract = {Abstract Bacterial biofilms have been observed in many prosthesis-related
infections, and this mode of growth renders the infection both difficult
to treat and especially difficult to detect and diagnose using standard
culture methods. We (1) tested a novel coupled PCR-mass spectrometric
(PCR-MS) assay (the Ibis T5000) on an ankle arthroplasty that was
culture negative on preoperative aspiration and then (2) confirmed
that the Ibis assay had in fact detected a viable multispecies biofilm
by further micrographic and molecular examinations, including confocal
microscopy using Live/Dead stain, bacterial FISH, and reverse-transcriptase-PCR
(RT-PCR) assay for bacterial mRNA. The Ibis technology detected Staphylococcus
aureus, Staphylococcus epidermidis, and the methicillin resistance
gene mecA in soft tissues associated with the explanted hardware.
Viable S. aureus were confirmed using RT-PCR, and viable cocci in
the biofilm configuration were detected microscopically on both tissue
and hardware. Species-specific bacterial FISH confirmed a polymicrobial
biofilm containing S. aureus. A novel culture method recovered S.
aureus and S. epidermidis (both methicillin resistant) from the tibial
metal component. These observations suggest that molecular methods,
particularly the new Ibis methodology, may be a useful adjunct to
routine cultures in the detection of biofilm bacteria in prosthetic
joint infection.},
doi = {10.1111/j.1574-695X.2011.00793.x},
issn = {1574-695X},
keywords = {biofilm, joint infection, prosthetic, arthroplasty, PCR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-695X.2011.00793.x}
}
@ARTICLE{Stoodley2008,
author = {Stoodley, Paul and Nistico, Laura and Johnson, Sandra and Lasko,
Leslie-Ann and Baratz, Mark and Gahlot, Vikram and Ehrlich, Garth
D. and Kathju, Sandeep},
title = {Direct Demonstration of Viable Staphylococcus aureus Biofilms in
an Infected Total Joint Arthroplasty. A Case Report},
journal = {J. Bone Joint Surg. Am.},
year = {2008},
volume = {90},
pages = {1751--1758},
number = {8},
month = aug,
url = {http://www.ejbjs.org}
}
@ARTICLE{Stopfer2004,
author = {Stopfer, Peter and Mannel, Daniela N. and Hehlgans, Thomas},
title = {Lymphotoxin-{beta} Receptor Activation by Activated T Cells Induces
Cytokine Release from Mouse Bone Marrow-Derived Mast Cells},
journal = {J. Immunol.},
year = {2004},
volume = {172},
pages = {7459--7465},
number = {12},
month = jun,
abstract = {Lymphotoxin-{beta} receptor (LT{beta}R) signaling is known to play
a key role in embryonic lymphoid organ formation as well as maintenance
of lymphoid architecture. Activation of the LT{beta}R is induced
by either the heterotrimeric lymphotoxin-{alpha}1{beta}2 (LT{alpha}1{beta}2)
or the homotrimeric LIGHT (homologous to lymphotoxins, exhibits inducible
expression, and competes with HSV gpD for herpes virus entry mediator,
a receptor expressed by T lymphocyte). Both ligands are expressed
on activated lymphocytes. As mast cells reside in close proximity
to activated T cells in some inflammatory tissues, we examined the
expression of LT{beta}R on bone marrow-derived mast cells and asked
whether the LT{beta}R-ligand interaction would allow communication
between mast cells and activated T cells. We found that mast cells
express LT{beta}R at the mRNA as well as at the protein level. To
investigate LT{beta}R-specific mast cell activation, the LT{beta}R
on BMMC from either wild-type or LT{beta}R-deficient mice was stimulated
with recombinant mouse LIGHT or agonistic mAbs in the presence of
ionomycin. LT{beta}R-specific release of the cytokines IL-4, IL-6,
TNF, and the chemokines macrophage inflammatory protein 2 and RANTES
was detected. Moreover, coculture of mast cells with T cells expressing
the LT{beta}R ligands also entailed the release of these cytokines.
Interference with a specific LT{beta}R inhibitor resulted in significant
suppression of mast cell cytokine release. These data clearly show
that LT{beta}R expressed on mast cells can transduce a costimulatory
signal in T cell-dependent mast cell activation.},
url = {http://www.jimmunol.org/cgi/content/abstract/172/12/7459}
}
@ARTICLE{Stopfer2004a,
author = {Stopfer, P. and Obermeier, F. and Dunger, N. and Falk, W. and Farkas,
S. and Janotta, M. and Möller, A. and Männel, D. N. and Hehlgans,
T.},
title = {Blocking lymphotoxin-β receptor activation diminishes inflammation
via reduced mucosal addressin cell adhesion molecule-1 (MAdCAM-1)
expression and leucocyte margination in chronic DSS-induced colitis},
journal = {Clinical \& Experimental Immunology},
year = {2004},
volume = {136},
pages = {21--29},
number = {1},
abstract = {SUMMARY The lymphotoxin-β receptor (LTβR) pathway is critical for
maintenance of organized lymphoid structures and is involved in the
development of colitis. To investigate the mechanisms by which LTβR
activation contributes to the pathology of chronic inflammation we
used a soluble LTβR-Ig fusion protein as a competitive inhibitor
of LTβR activation in the mouse model of chronic colitis induced
by oral administration of dextran sulphate sodium. Strong expression
of LTβ which constitutes part of the LTα1β2 ligand complex was
detected in colonic tissue of mice with chronic colitis. Treatment
with LTβR-Ig significantly attenuated the development and histological
manifestations of the chronic inflammation and reduced the production
of inflammatory cytokines such as TNF, IL-1β, and IL-6. Moreover,
LTβR-Ig treatment significantly down-regulated mucosal addressin
cell adhesion molecule-1 (MAdCAM-1) expression, leading to reduced
leucocyte rolling and sticking in postcapillary and collecting venules
and reduced extravasation into the intestinal mucosa as quantified
by in vivo fluorescence microscopy. Thus, LTβR pathway inhibition
ameliorates DSS-induced experimental chronic colitis in mice by MAdCAM-1
down-regulation entailing reduced lymphocyte margination and extravasation
into the inflamed mucosa. Therefore, a combined treatment with reagents
blocking T cell-mediated perpetuation of chronic inflammation such
as LTβR-Ig together with direct anti-inflammatory reagents such
as TNF inhibitors could constitute a promising treatment strategy
for chronic colitis.},
issn = {1365-2249},
keywords = {DSS-induced colitis, LIGHT, LTα1β2, LTβR, MAdCAM-1},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2249.2004.02402.x}
}
@ARTICLE{Storey2007,
author = {Storey, John D. and Madeoy, Jennifer and Strout, Jeanna L. and Wurfel,
Mark and Ronald, James and Akey, Joshua M.},
title = {Gene-Expression Variation Within and Among Human Populations},
journal = {The American Journal of Human Genetics},
year = {2007},
volume = {80},
pages = {502--509},
number = {3},
month = mar,
abstract = {Understanding patterns of gene-expression variation within and among
human populations will provide important insights into the molecular
basis of phenotypic diversity and the interpretation of patterns
of expression variation in disease. However, little is known about
how gene-expression variation is apportioned within and among human
populations. Here, we characterize patterns of natural gene-expression
variation in 16 individuals of European and African ancestry. We
find extensive variation in gene-expression levels and estimate that
~83% of genes are differentially expressed among individuals and
that ~17% of genes are differentially expressed among populations.
By decomposing total gene-expression variation into within- versus
among-population components, we find that most expression variation
is due to variation among individuals rather than among populations,
which parallels observations of extant patterns of human genetic
variation. Finally, we performed allele-specific quantitative polymerase
chain reaction to demonstrate that cis-regulatory variation in the
lymphocyte adaptor protein (SH2B adapter protein 3) contributes to
differential expression between European and African samples. These
results provide the first insight into how human population structure
manifests itself in gene-expression levels and will help guide the
search for regulatory quantitative trait loci.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4RDPP3P-D/2/2ed04a86f69ab9c2c1f8851e3230b616}
}
@ARTICLE{Storr2011,
author = {Sarah J. Storr and Rabab A.A. Mohammed and Caroline M. Woolston and
Andrew R. Green and Tim Parr and Inmaculada Spiteri and Carlos Caldas
and Graham R. Ball and Ian O. Ellis and Stewart G. Martin},
title = {Calpastatin is associated with lymphovascular invasion in breast
cancer},
journal = {The Breast},
year = {2011},
volume = {20},
pages = {413 - 418},
number = {5},
abstract = {Metastasis of breast cancer is a major contributor to mortality. Histological
assessment of vascular invasion (VI) provides important prognostic
information and demonstrates that VI occurs predominantly via lymphatics
in breast cancer. We sought to examine genes and proteins involved
in lymphovascular invasion (LVI) to understand the mechanisms of
this key disease process. A gene expression array of 91 breast cancer
patients was analysed by an Artificial Neural Network (ANN) approach
using LVI to supervise the analysis. 89 transcripts were significantly
associated (p < 0.001) with the presence of LVI. Calpastatin,
a specific calpain inhibitor, had the second lowest selection error
and was investigated in breast cancer specimens using real-time PCR
(n = 56) and immunohistochemistry (n = 53). Both calpastatin
mRNA and protein levels were significantly associated with the presence
of LVI (p = 0.014 and p = 0.025 respectively). The data supports
the hypothesis that calpastatin may play a role in regulating the
initial metastatic dissemination of breast cancer.},
doi = {10.1016/j.breast.2011.04.002},
issn = {0960-9776},
keywords = {Breast cancer},
url = {http://www.sciencedirect.com/science/article/pii/S0960977611000920}
}
@ARTICLE{Storvik2010,
author = {Storvik, Markus and Arguel, Marie-Jeanne and Schmieder, Sandra and
Delerue-Audegond, Audrey and Li, Qin and Qin, Chuan and Vital, Anne
and Bioulac, Bernard and Gross, Christian E. and Wong, Garry and
Nahon, Jean-Louis and Bezard, Erwan},
title = {Genes regulated in MPTP-treated macaques and human Parkinson's disease
suggest a common signature in prefrontal cortex},
journal = {Neurobiology of Disease},
year = {2010},
volume = {38},
pages = {386--394},
number = {3},
month = jun,
abstract = {The presymptomatic phase of Parkinson's disease (PD) is now recognized
as a prodromal phase, with compensatory mechanism masking its progression
and non-motor early manifestations, such as depression, cognitive
disturbances and apathy. Those mechanisms were thought to be strictly
dopamine-mediated until recent advances have shed light upon involvement
of putative outside-basal ganglia, i.e. cortical, structures. We
took advantage of our progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated macaque model to monitor whole genome transcriptional
changes in several brain areas. Our data reveals that transcriptomic
activity changes take place from early stages, suggesting very early
compensatory mechanisms or pathological activity outside the basal
ganglia, including the PFC. Specific transcriptomic changes occurring
in the PFC of fully parkinsonian MPTP-treated macaques have been
identified. Interestingly, a large part of these transcriptomic changes
were also observed in human post-mortem samples of patients with
neurodegenerative diseases analysed by quantitative PCR. These results
suggest that the PFC is able to detect the progression of dopamine
denervation even at very early time points. There are therefore mechanisms,
within the PFC, leading to compensatory alterations and/or participating
to pathophysiology of prodromal PD manifestations.},
booktitle = {Frontiers in Brain Stimulation},
issn = {0969-9961},
keywords = {Microarray, Quantitative PCR, Monkey, Human, Parkinson's disease,
MPTP, Brain, Prefrontal cortex},
url = {http://www.sciencedirect.com/science/article/B6WNK-4YH99M8-1/2/9163c05f64c35c6bfa88ee83e6eb3347}
}
@ARTICLE{Stoss2006,
author = {Stoss, O. and Albers, P. and Werther, M. and Zielinsky, D. and Jost,
N. and Rueschoff, J. and Henkel, T.},
title = {Gene profiling in transurethral resection samples of patients with
hormone-refractory prostate cancer (HRPC)},
journal = {ASCO Meeting Abstracts},
year = {2006},
volume = {24},
pages = {4641--},
number = {18_suppl},
month = jun,
abstract = {4641 Background: Patients with metastatic carcinoma of the prostate
(CaP) develop after a mean of 15 months resistance to hormone ablation
therapy. However, the underlying molecular mechanisms are still unknown.
Our goal was to identify the transcriptional changes that are characteristic
for the transition to hormone resistant prostate cancer (HRPC) using
oligonucleotide microarrays. Here, we report the attempt to profile
fresh frozen tissue obtained by palliative transurethral resection
(TUR) in patients with HRPC and concomittant urinary obstruction.
Methods: Indications for palliative TUR were locally progressive
tumors with obstruction and voiding problems. HRPC was defined according
to the criteria of Scher et al. 1995. Samples of 8 HRPC patients
were compared to tissues from 8 hormone-sensitive CaP patients including
biological and technical replicates. All tissue samples had been
pathologically evaluated. Only macrodissected prostate samples with
at least 70% tumor content were used for RNA extraction. RNA quality
was controlled using the Bioanalyzer Nanochip (Agilent Technologies,
Palo Alto). Expression analysis was performed on Affymetrix oligonucleotide
arrays. Results: We identified 323 genes being significantly deregulated
(corrected p-value <0.05, false discovery rate <0.05). These genes
were mapped to cellular pathways using the KEGG annotation and the
most significantly deregulated pathways were identified. Deregulation
of metabolic pathways included fatty acid metabolism as well as oxidative
phosphorylation and ATP synthesis. Cell cycle control seems to be
further suppressed by the downregulation of JNK-pathway via MEKK4
and JUND, the downregulation of p21 (CDKN1A) and the induction of
Cylcin D1. We also present evidence for a significant downregulation
of actin cyctoskeleton components. Deregulated genes likely to be
specific for the transition from prostate carcinoma to HRPC will
be presented. Conclusions: Gene expression profiling has been successfully
standardised using fresh TUR material of HRPC patients. Deregulated
genes have been mapped to specific signal transduction pathways.
On this platform, clinical trials in patients with HRPC using specific
inhibitors of cell signalling are being developed. Author Disclosure
Employment or Leadership Consultant or Advisory Role Stock Ownership
Honoraria Research Funding Expert Testimony Other Remuneration Novartis},
url = {http://meeting.ascopubs.org/cgi/content/abstract/24/18_suppl/4641}
}
@ARTICLE{Stoss2007,
author = {Stoss, O. and Zielinski, D. and Czeloth, K. and Middel, P. and Henkel,
T. and Albers, P.},
title = {Molecular analysis of hormone refractory prostate cancer biopsies
supports the rationale of using mTOR inhibitors},
journal = {ASCO Meeting Abstracts},
year = {2007},
volume = {25},
pages = {21126--},
number = {18_suppl},
month = jun,
abstract = {21126 Background: The aim of our group is to identify molecular signatures
in samples of hormone refractory prostate cancer (HRPC) patients
(pts) that lead to novel rationales for medical treatment. We have
previously shown that transurethral resections (TUR) of the prostate
in HRPC pts are useful specimens for gene expression profiling using
microarrays (ASCO 2006). Aim of this study was to prove the feasibility
of gene expression profiling on prostate biopsies and to develop
a standardised tissue handling protocol in order to facilitate multicenter
research. Methods: Biopsy material and corresponding TUR chips or
classical specimens from 8 pts with HRPC, 13 pts with localized PCA,
6 pts with benign prostatic hyperplasia (BPH) and 11 pts without
cancer or BPH were investigated and compared. The tumor type and
content was evaluated by a pathologist. Tissues were preserved in
liquid nitrogen or RNAlater. Different tissue lysis and RNA purification
methods were compared by the quantity (NanoDrop measurement) and
quality (Bioanalyser, Agilent) of isolated RNA. Gene expression profiling
occurred on Affymetrix HG-FOCUS arrays. Results: Most reliable gene
expression results were obtained by biopsy lysis in Trizol using
the QIAshredder. A total of more than 1 {micro}g RNA was isolated
from one biopsy. RNA quality fulfilled pre-defined criteria such
as a 28S/18S rRNA ratio of > 0.8, an area under the curve of > 10%
and a RNA integrity number > 6.5. A comparison of HRPC and PCA samples
clearly confirmed previous results of a deregulation of protein biosynthesis
(translation initiation and elongation factors, ribosome biogenesis)
and PI3K signalling pathway components. Conclusions: Gene expression
profiling supports the induction of the PI3K-AKT-mTOR pathway in
HRPC. A standardised protocol for gene expression profiling from
prostate biopsy samples applicable for translational research programs
within multicenter clinical trials is now available. As a part of
a clinical phase II trial that aims to investigate survival benefits
on HRPC pts treated with docetaxel {+/-} RAD001, a translational
research program is now set up in parallel to identify biomarkers
for response prediction using microarray gene expression analysis
from prostate biopsies. No significant financial relationships to
disclose.},
url = {http://meeting.ascopubs.org/cgi/content/abstract/25/18_suppl/21126}
}
@ARTICLE{Stothard2011,
author = {Stothard, Paul and Choi, Jung-Woo and Basu, Urmila and Sumner-Thomson,
Jennifer and Meng, Yan and Liao, Xiaoping and Moore, Stephen},
title = {Whole genome resequencing of black Angus and Holstein cattle for
SNP and CNV discovery},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {559},
number = {1},
abstract = {BACKGROUND:One of the goals of livestock genomics research is to identify
the genetic differences responsible for variation in phenotypic traits,
particularly those of economic importance. Characterizing the genetic
variation in livestock species is an important step towards linking
genes or genomic regions with phenotypes. The completion of the bovine
genome sequence and recent advances in DNA sequencing technology
allow for in-depth characterization of the genetic variations present
in cattle. Here we describe the whole-genome resequencing of two
Bos taurus bulls from distinct breeds for the purpose of identifying
and annotating novel forms of genetic variation in cattle.RESULTS:The
genomes of a Black Angus bull and a Holstein bull were sequenced
to 22-fold and 19-fold coverage, respectively, using the ABI SOLiD
system. Comparisons of the sequences with the Btau4.0 reference assembly
yielded 7 million single nucleotide polymorphisms (SNPs), 24% of
which were identified in both animals. Of the total SNPs found in
Holstein, Black Angus, and in both animals, 81%, 81%, and 75% respectively
are novel. In-depth annotations of the data identified more than
16 thousand distinct non-synonymous SNPs (85% novel) between the
two datasets. Alignments between the SNP-altered proteins and orthologues
from numerous species indicate that many of the SNPs alter well-conserved
amino acids. Several SNPs predicted to create or remove stop codons
were also found. A comparison between the sequencing SNPs and genotyping
results from the BovineHD high-density genotyping chip indicates
a detection rate of 91% for homozygous SNPs and 81% for heterozygous
SNPs. The false positive rate is estimated to be about 2% for both
the Black Angus and Holstein SNP sets, based on follow-up genotyping
of 422 and 427 SNPs, respectively. Comparisons of read depth between
the two bulls along the reference assembly identified 790 putative
copy-number variations (CNVs). Ten randomly selected CNVs, five genic
and five non-genic, were successfully validated using quantitative
real-time PCR. The CNVs are enriched for immune system genes and
include genes that may contribute to lactation capacity. The majority
of the CNVs (69%) were detected as regions with higher abundance
in the Holstein bull.CONCLUSIONS:Substantial genetic differences
exist between the Black Angus and Holstein animals sequenced in this
work and the Hereford reference sequence, and some of this variation
is predicted to affect evolutionarily conserved amino acids or gene
copy number. The deeply annotated SNPs and CNVs identified in this
resequencing study can serve as useful genetic tools, and as candidates
in searches for phenotype-altering DNA differences.},
doi = {10.1186/1471-2164-12-559},
issn = {1471-2164},
pubmedid = {22085807},
url = {http://www.biomedcentral.com/1471-2164/12/559}
}
@ARTICLE{Stotz2011,
author = {Stotz, Henrik U. and Sawada, Yuji and Shimada, Yukihisa and Hirai,
Masami Y. and Sasaki, Eriko and Krischke, Markus and Brown, Paul
D. and Saito, Kazuki and Kamiya, Yuji},
title = {Role of camalexin, indole glucosinolates, and side chain modification
of glucosinolate-derived isothiocyanates in defense of Arabidopsis
against Sclerotinia sclerotiorum},
journal = {The Plant Journal},
year = {2011},
volume = {67},
pages = {81--93},
number = {1},
abstract = {Plant secondary metabolites are known to facilitate interactions with
a variety of beneficial and detrimental organisms, yet the contribution
of specific metabolites to interactions with fungal pathogens is
poorly understood. Here we show that, with respect to aliphatic glucosinolate-derived
isothiocyanates, toxicity against the pathogenic ascomycete Sclerotinia
sclerotiorum depends on side chain structure. Genes associated with
the formation of the secondary metabolites camalexin and glucosinolate
were induced in Arabidopsis thaliana leaves challenged with the necrotrophic
pathogen S. sclerotiorum. Unlike S. sclerotiorum, the closely related
ascomycete Botrytis cinerea was not identified to induce genes associated
with aliphatic glucosinolate biosynthesis in pathogen-challenged
leaves. Mutant plant lines deficient in camalexin, indole, or aliphatic
glucosinolate biosynthesis were hypersusceptible to S. sclerotiorum,
among them the myb28 mutant, which has a regulatory defect resulting
in decreased production of long-chained aliphatic glucosinolates.
The antimicrobial activity of aliphatic glucosinolate-derived isothiocyanates
was dependent on side chain elongation and modification, with 8-methylsulfinyloctyl
isothiocyanate being most toxic to S. sclerotiorum. This information
is important for microbial associations with cruciferous host plants
and for metabolic engineering of pathogen defenses in cruciferous
plants that produce short-chained aliphatic glucosinolates.},
doi = {10.1111/j.1365-313X.2011.04578.x},
issn = {1365-313X},
keywords = {mustard oil bomb, glucosinolate structure and function, natural plant
products, necrotrophic ascomycetes, white mold, antifungal activity},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2011.04578.x}
}
@ARTICLE{Stowers2007,
author = {Stowers, Chris C. and Boczko, Erik M.},
title = {Reliable cell disruption in yeast},
journal = {Yeast},
year = {2007},
volume = {24},
pages = {533--541},
number = {6},
abstract = {Abstract 10.1002/yea.1491.abs We report the results of an optical
assay to determine the degree of cell wall disruption in yeast. The
results indicate that cell wall disruption with glass beads yields
reproducible results that can be modelled with an integral measure
of time to failure that implies a decreasing failure rate. It is
shown that a standard protocol results in only 60% disruption, with
a relatively large coefficient of variation. The data show that the
yield of total RNA harvested is proportional to the degree of cellular
disruption, and that there is no loss of RNA quality with > 90% disruption.
The data also show that cell disruption of a synchronous culture
varies with the cell cycle. We speculate that the decreasing failure
rate is related to the cell cycle phase-dependent disruptability.
Copyright © 2007 John Wiley & Sons, Ltd.},
issn = {1097-0061},
keywords = {RNA extraction, protein purification, quantitative biology, Weibull
distribution, aniline blue},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/yea.1491}
}
@ARTICLE{Straat2009,
author = {Straat, Klas and de Klark, Rainier and Gredmark-Russ, Sara and Eriksson,
Per and Soderberg-Naucler, Cecilia},
title = {Infection with Human Cytomegalovirus Alters the MMP-9/TIMP-1 Balance
in Human Macrophages},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {830--835},
number = {2},
month = jan,
abstract = {Human cytomegalovirus (HCMV) has been suggested to contribute to the
development of vascular diseases. Since matrix metalloproteinases
(MMPs) have been implicated in atherosclerosis and plaque rupture,
we investigated the effect of HCMV infection on MMP expression in
human macrophages. We used quantitative real-time PCR, Western blotting,
and gelatin zymography to study the expression and activity of MMP-2,
-3, -7, -9, -12, -13, and -14 and of tissue inhibitor of metalloproteinase
1 (TIMP-1), -2, -3, and -4. HCMV infection reduced MMP-9 mRNA, protein,
and activity levels but increased TIMP-1 mRNA and protein levels.
Furthermore, a decrease in MMP-12, MMP-14, TIMP-2, and TIMP-3 mRNA
levels could be detected. The MMP-9 and TIMP-1 mRNA alterations required
viral replication. MMP-9 mRNA expression was affected by an immediate-early
or early viral gene product, whereas TIMP-1 mRNA expression was affected
by late viral gene products. We conclude that HCMV infection specifically
alters the MMP-9/TIMP-1 balance in human macrophages, which in turn
reduces MMP-9 activity in infected cells. Since MMP-9 prevents atherosclerotic
plaque development in mice, these results suggest that HCMV may contribute
to atherogenesis through specific effects on MMP-9 activity.},
url = {http://jvi.asm.org/cgi/content/abstract/83/2/830}
}
@ARTICLE{Strasser2010,
author = {Strasser, Geraldine A. and Kaminker, Joshua S. and Tessier-Lavigne,
Marc},
title = {Microarray analysis of retinal endothelial tip cells identifies CXCR4
as a mediator of tip cell morphology and branching},
journal = {Blood},
year = {2010},
volume = {115},
pages = {5102--5110},
number = {24},
month = jun,
abstract = {The development of the vertebrate vascular system is mediated by both
genetic patterning of vessels and by angiogenic sprouting in response
to hypoxia. Both of these processes depend on the detection of environmental
guidance cues by endothelial cells. A specialized subtype of endothelial
cell known as the tip cell is thought to be involved in the detection
and response to these cues, but the molecular signaling pathways
used by tip cells to mediate tissue vascularization remain largely
uncharacterized. To identify genes critical to tip cell function,
we have developed a method to isolate them using laser capture microdissection,
permitting comparison of RNA extracted from endothelial tip cells
with that of endothelial stalk cells using microarray analysis. Genes
enriched in tip cells include ESM-1, angiopoietin-2, and SLP-76.
CXCR4, a receptor for the chemokine stromal-cell derived factor-1,
was also identified as a tip cell-enriched gene, and we provide evidence
for a novel role for this receptor in mediating tip cell morphology
and vascular patterning in the neonatal retina.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/24/5102}
}
@ARTICLE{Strat2006,
author = {Strat, Aurel and Gao, Lu and Utsuki, Tada and Cheng, Bing and Nuthalapaty,
Sam and Mathis, J. Mike and Odaka, Yoshinobu and Giordano, Tony},
title = {Specific and nontoxic silencing in mammalian cells with expressed
long dsRNAs},
journal = {Nucleic Acids Res.},
year = {2006},
volume = {34},
pages = {3803--3810},
number = {13},
month = aug,
abstract = {A number of groups have developed libraries of siRNAs to identify
genes through functional genomics. While these studies have validated
the approach of making functional RNAi libraries to understand fundamental
cellular mechanisms, they require information and knowledge of existing
sequences since the RNAi sequences are generated synthetically. An
alternative strategy would be to create an RNAi library from cDNA.
Unfortunately, the complexity of such a library of siRNAs would make
screening difficult. To reduce the complexity, longer dsRNAs could
be used; however, concerns of induction of the interferon response
and off-target effects of long dsRNAs have prevented their use. As
a first step in creating such libraries, long dsRNA was expressed
in mammalian cells. The 250 nt dsRNAs were capable of efficiently
silencing a luciferase reporter gene that was stably transfected
in MDA-MB-231 cells without inducing the interferon response or off-target
effects any more than reported for siRNAs. In addition, a long dsRNA
expressed in the same cell line was capable of silencing endogenous
c-met expression and inhibited cell migration, whereas the dsRNA
against luciferase had no effect on c-met or cell migration. The
studies suggest that large dsRNA libraries are feasible and that
functional selection of genes will be possible.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/34/13/3803}
}
@ARTICLE{Stratmann2011,
author = {Stratmann, Johannes and Wang, Chao-Jie and Gnosa, Sebastian and Wallin,
Asa and Hinselwood, David and Sun, Xiao-Feng and Zhang, Hong},
title = {Dicer and miRNA in relation to clinicopathological variables in colorectal
cancer patients},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {345},
number = {1},
abstract = {BACKGROUND:Dicer is aberrantly expressed in several types of cancers.
Applying real-time PCR, we detected the expression of Dicer mRNA
in normal mucosa (n = 162), primary colorectal cancer (CRC) (n =
162) and liver metastasis (n = 37), and analysed the relationship
between Dicer expression and clinicopathological features. We also
correlated the expression of Dicer mRNA to the miRNA expression of
miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.METHODS:RT-PCR
and qPCR were used to analyse the Dicer expression in normal mucosa,
primary tumour and liver metastasis by using the High Capacity cDNA
Reverse Transcription Kit and TaqManTM(R) Gene Expression assays
for Dicer and GAPDH. RT-PCR and qPCR were used to detect miRNA expression
in liver metastases by utilizing TaqMan(R) MicroRNA Reverse Transcription
Kit and TaqMan(R) miRNA Assays. Statistical analyses were performed
with STATISTICA.RESULTS:Dicer expression in rectal cancer (3.146
+/- 0.953) was higher than in colon cancer (2.703 +/- 1.204, P =
0.018). Furthermore the Dicer expression was increased in primary
tumours (3.146 +/- 0.952) in comparison to that in normal mucosa
from rectal cancer patients (2.816 +/- 1.009, P = 0.034) but this
is not evident in colon cancer patients. Dicer expression in liver
metastases was decreased in comparison to that of either normal mucosa
or primary tumour in both colon and rectal cancers (P < 0.05). Patients
with a high Dicer expression in normal mucosa had a worse prognosis
compared to those with a low Dicer expression, independently of gender,
age, tumour site, stage and differentiation (P < 0.001, RR 3.682,
95% CI 1.749 - 7.750). In liver metastases, Dicer was positively
related to miR-141 (R = 0.419, P = 0.015).CONCLUSION:Dicer is up-regulated
in the early development of rectal cancers. An increased expression
of Dicer mRNA in normal mucosa from CRC patients is significantly
related to poor survival independently of gender, age, tumour site,
stage and differentiation.},
doi = {10.1186/1471-2407-11-345},
issn = {1471-2407},
pubmedid = {21827717},
url = {http://www.biomedcentral.com/1471-2407/11/345}
}
@ARTICLE{Streefland2009,
author = {Streefland, M. and Van Herpen, P.F.G. and Van de Waterbeemd, B. and
Van der Pol, L.A. and Beuvery, E.C. and Tramper, J. and Martens,
D.E. and Toft, M.},
title = {A practical approach for exploration and modeling of the design space
of a bacterial vaccine cultivation process},
journal = {Biotechnol. Bioeng.},
year = {2009},
volume = {104},
pages = {492--504},
number = {3},
abstract = {Abstract 10.1002/bit.22425.abs A licensed pharmaceutical process is
required to be executed within the validated ranges throughout the
lifetime of product manufacturing. Changes to the process, especially
for processes involving biological products, usually require the
manufacturer to demonstrate that the safety and efficacy of the product
remains unchanged by new or additional clinical testing. Recent changes
in the regulations for pharmaceutical processing allow broader ranges
of process settings to be submitted for regulatory approval, the
so-called process design space, which means that a manufacturer can
optimize his process within the submitted ranges after the product
has entered the market, which allows flexible processes. In this
article, the applicability of this concept of the process design
space is investigated for the cultivation process step for a vaccine
against whooping cough disease. An experimental design (DoE) is applied
to investigate the ranges of critical process parameters that still
result in a product that meets specifications. The on-line process
data, including near infrared spectroscopy, are used to build a descriptive
model of the processes used in the experimental design. Finally,
the data of all processes are integrated in a multivariate batch
monitoring model that represents the investigated process design
space. This article demonstrates how the general principles of PAT
and process design space can be applied for an undefined biological
product such as a whole cell vaccine. The approach chosen for model
development described here, allows on line monitoring and control
of cultivation batches in order to assure in real time that a process
is running within the process design space. Biotechnol. Bioeng. 2009;
104: 492–504 © 2009 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {process analytical technology, PAT, Bordetella pertussis, process
design space, process model, cultivation, DoE},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22425}
}
@ARTICLE{Streefland2007,
author = {Streefland, Mathieu and van de Waterbeemd, Bas and Happé, Hester
and van der Pol, Leo A. and Beuvery, E. Coen and Tramper, Johannes
and Martens, Dirk E.},
title = {PAT for vaccines: The first stage of PAT implementation for development
of a well-defined whole-cell vaccine against whooping cough disease},
journal = {Vaccine},
year = {2007},
volume = {25},
pages = {2994--3000},
number = {16},
month = apr,
abstract = {Since variation in process time and process output is commonly accepted
to be inevitable for biological processes, application of Process
Analytical Technologies (PAT) on these processes is challenging.
In this paper the applicability of PAT on the cultivation of Bordetella
pertussis bacteria as part of the manufacture of a vaccine against
whooping cough disease is investigated. Scrutinizing and eliminating
the most prominent sources of variance make the cultivation process
step highly reproducible. Furthermore, the use of DNA microarrays
allows investigation of how disturbances influence cellular physiology
and product quality. Marker genes for product quality were identified,
providing the means to quantitatively assess product quality, which
is hardly possible using the mandatory animal tests for product quality.
The tools and results described in this paper, combined with suitable
on line measurements, can make full PAT application for this process
step possible. Ultimately, the process can be designed and controlled
towards consistent end product quality.},
booktitle = {Vaccines, Immunisation and Immunotherapy - Based on the Fifth World
Congress on Vaccines, Immunisation and Immunotherapy},
issn = {0264-410X},
keywords = {Process Analytical Technology, Bordetella pertussis, Bioreactor, Cultivation,
Microarray, Virulence, Product quality},
url = {http://www.sciencedirect.com/science/article/B6TD4-4MW8WKS-8/2/ca534b4031ab1b35b67c1e9c1b5e48fd}
}
@ARTICLE{Streefland2009a,
author = {Streefland, Mathieu and van de Waterbeemd, Bas and Kint, Joeri and
van der Pol, Leo A. and Beuvery, E. Coen and Tramper, Johannes and
Martens, Dirk E.},
title = {Evaluation of a critical process parameter: Oxygen limitation during
cultivation has a fully reversible effect on gene expression of Bordetella
pertussis},
journal = {Biotechnol. Bioeng.},
year = {2009},
volume = {102},
pages = {161--167},
number = {1},
abstract = {Abstract 10.1002/bit.22030.abs Modern (bio)pharmaceutical process
development requires thorough investigation of all process parameters
that are critical to product quality. The impact of a disturbance
of such a parameter during processing needs to be known so that a
rational decision can be made about the release of the product. In
cultivation processes the dissolved oxygen (DO) concentration is
generally accepted as being a critical parameter. In this article
the impact of a 90 min period of oxygen limitation during the cultivation
of the strictly aerobic Bordetella pertussis bacterium is investigated.
The cultivation is the most important process step for the manufacturing
of a vaccine against whooping cough disease. Samples were taken immediately
before and after oxygen limitation and at the end of cultivation
of four oxygen limited and three control cultivations. DNA microarray
analysis of the full transcriptome of the B. pertussis bacterium
revealed that a 90 min period of oxygen limitation has a substantial
effect on overall gene expression patterns. In total 104 genes were
identified as a significant hit at any of the sample points, of which
58 were directly related to oxygen limitation. The other genes were
mainly affected towards the end of cultivation. Of all genes involved
in oxygen limitation none were identified to show a significant difference
between the oxygen limited and control cultivations at the end of
the batch. This indicates a fully reversible effect of oxygen limitation
on gene expression. This finding has implications for the risk assessment
of dissolved oxygen concentration as a critical process parameter.
Biotechnol. Bioeng. 2009;102: 161–167. © 2008 Wiley Periodicals,
Inc.},
issn = {1097-0290},
keywords = {process analytical technology, PAT, Bordetella pertussis, vaccine,
cultivation, biopharmaceutical, DNA microarray, virulence, oxygen
limitation, dissolved oxygen concentration},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22030}
}
@ARTICLE{Street2006,
author = {Street, Nathaniel Robert and Skogström, Oskar and Sjödin, Andreas
and Tucker, James and RodrÃguez-Acosta, Maricela and Nilsson, Peter
and Jansson, Stefan and Taylor, Gail},
title = {The genetics and genomics of the drought response in Populus},
journal = {The Plant Journal},
year = {2006},
volume = {48},
pages = {321--341},
number = {3},
abstract = {Summary The genetic nature of tree adaptation to drought stress was
examined by utilizing variation in the drought response of a full-sib
second generation (F2) mapping population from a cross between Populus
trichocarpa (93-968) and P. deltoides Bart (ILL-129) and known to
be highly divergent for a vast range of phenotypic traits. We combined
phenotyping, quantitative trait loci (QTL) analysis and microarray
experiments to demonstrate that ‘genetical genomics’ can be used
to provide information on adaptation at the species level. The grandparents
and F2 population were subjected to soil drying, and contrasting
responses to drought across genotypes, including leaf coloration,
expansion and abscission, were observed, and QTL for these traits
mapped. A subset of extreme genotypes exhibiting extreme sensitivity
and insensitivity to drought on the basis of leaf abscission were
defined, and microarray experiments conducted on these genotypes
and the grandparent species. The extreme genotype groups induced
a different set of genes: 215 and 125 genes differed in their expression
response between groups in control and drought, respectively, suggesting
species adaptation at the gene expression level. Co-location of differentially
expressed genes with drought-specific and drought-responsive QTLs
was examined, and these may represent candidate genes contributing
to the variation in drought response.},
issn = {1365-313X},
keywords = {poplar, microarray, QTL, transcriptome, drought},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2006.02864.x}
}
@ARTICLE{Strefford2006,
author = {Strefford, Jon C. and van Delft, Frederik W. and Robinson, Hazel
M. and Worley, Helen and Yiannikouris, Olga and Selzer, Rebecca and
Richmond, Todd and Hann, Ian and Bellotti, Tony and Raghavan, Manoj
and Young, Bryan D. and Saha, Vaskar and Harrison, Christine J.},
title = {Complex genomic alterations and gene expression in acute lymphoblastic
leukemia with intrachromosomal amplification of chromosome 21},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {8167--8172},
number = {21},
month = may,
abstract = {We have previously identified a unique subtype of acute lymphoblastic
leukemia (ALL) associated with a poor outcome and characterized by
intrachromosomal amplification of chromosome 21 including the RUNX1
gene (iAMP21). In this study, array-based comparative genomic hybridization
(aCGH) (n = 10) detected a common region of amplification (CRA) between
33.192 and 39.796 Mb and a common region of deletion (CRD) between
43.7 and 47 Mb in 100% and 70% of iAMP21 patients, respectively.
High-resolution genotypic analysis (n = 3) identified allelic imbalances
in the CRA. Supervised gene expression analysis showed a distinct
signature for eight patients with iAMP21, with 10% of overexpressed
genes located within the CRA. The mean expression of these genes
was significantly higher in iAMP21 when compared to other ALL samples
(n = 45). Although genomic copy number correlated with overall gene
expression levels within areas of loss or gain, there was considerable
individual variation. A unique subset of differentially expressed
genes, outside the CRA and CRD, were identified when gene expression
signatures of iAMP21 were compared to ALL samples with ETV6-RUNX1
fusion (n = 21) or high hyperdiploidy with additional chromosomes
21 (n = 23). From this analysis, LGMN was shown to be overexpressed
in patients with iAMP21 (P = 0.0012). Genomic and expression data
has further characterized this ALL subtype, demonstrating high levels
of 21q instability in these patients leading to proposals for mechanisms
underlying this clinical phenotype and plausible alternative treatments.},
url = {http://www.pnas.org/cgi/content/abstract/103/21/8167}
}
@ARTICLE{Strickland2011,
author = {E.R. Strickland and M.A. Hook and S. Balaraman and J.R. Huie and
J.W. Grau and R.C. Miranda},
title = {MicroRNA dysregulation following spinal cord contusion: implications
for neural plasticity and repair},
journal = {Neuroscience},
year = {2011},
volume = {186},
pages = {146 - 160},
number = {0},
abstract = {Spinal cord injury (SCI) is medically and socioeconomically debilitating.
Currently, there is a paucity of effective therapies that promote
regeneration at the injury site, and limited understanding of mechanisms
that can be utilized to therapeutically manipulate spinal cord plasticity.
MicroRNAs (miRNAs) constitute novel targets for therapeutic intervention
to promote repair and regeneration. Microarray comparisons of the
injury sites of contused and sham rat spinal cords, harvested 4 and
14 days following SCI, showed that 32 miRNAs, including miR124, miR129,
and miR1, were significantly down-regulated, whereas SNORD2, a translation-initiation
factor, was induced. Additionally, three miRNAs including miR21 were
significantly induced, indicating adaptive induction of an anti-apoptotic
response in the injured cord. Validation of miRNA expression by qRT-PCR
and in situ hybridization assays revealed that the influence of SCI
on miRNA expression persists up to 14 days and expands both anteriorly
and caudally beyond the lesion site. Specifically, changes in miR129-2
and miR146a expression significantly explained the variability in
initial injury severity, suggesting that these specific miRNAs may
serve as biomarkers and therapeutic targets for SCI. Moreover, the
pattern of miRNA changes coincided spatially and temporally with
the appearance of SOX2, nestin, and REST immunoreactivity, suggesting
that aberrant expression of these miRNAs may not only reflect the
emergence of stem cell niches, but also the reemergence in surviving
neurons of a pre-neuronal phenotype. Finally, bioinformatics analysis
of validated miRNA-targeted genes indicates that miRNA dysregulation
may explain apoptosis susceptibility and aberrant cell cycle associated
with a loss of neuronal identity, which underlies the pathogenesis
of secondary SCI.},
doi = {10.1016/j.neuroscience.2011.03.063},
issn = {0306-4522},
keywords = {spinal cord contusion},
url = {http://www.sciencedirect.com/science/article/pii/S030645221100371X}
}
@ARTICLE{Stringer2008,
author = {Stringer, Kathleen A and Tobias, Meghan and Dunn, John S and Campos,
Jackie and Van Rheen, Zachary and Mosharraf, Mitra and Nayar, Rajiv},
title = {Accelerated dosing frequency of a pulmonary formulation of tissue
plasminogen activator is well-tolerated in mice},
journal = {Clinical and Experimental Pharmacology and Physiology},
year = {2008},
volume = {35},
pages = {1454--1460},
number = {12},
abstract = {SUMMARY * 1Tissue plasminogen activator (tPA) has both fibrinolytic
and anti-inflammatory activity. These properties may be useful in
treating inflammatory lung diseases, such as acute respiratory distress
syndrome (ARDS). * 2We have previously demonstrated the feasibility
of targeted pulmonary delivery of tPA. As part of our research to
develop a clinically viable pulmonary formulation of tPA, we assessed
the tolerability and incidence of haemorrhage associated with the
administration of a pulmonary formulation of mouse tPA (pf-mtPA).
* 3Intratracheal doses of nebulized pf-mtPA or sterile saline were
administered with increasing frequency to male and female B6C3F1
mice. After dosing, the mice entered a recovery period, after which
they were killed and their lungs were lavaged and harvested. Post-mortem
gross necropsy was performed and all major organs were assessed histologically
for haemorrhage. The bronchoalveolar lavage fluid was assessed for
markers of lung injury. * 4Mouse tPA that was formulated to mimic
a previously characterized human pf-tPA was well tolerated when given
intratracheally with increasing dosing frequency. The administration
of pf-mtPA did not result in any detectable haemorrhagic-related
events or signs of lung injury. * 5The results of the present longitudinal
study demonstrate that a maximally feasible dose of pf-mtPA (3Â mg/kg)
can be given frequently over a short period of time (12Â h) without
haemorrhagic complications. Although these data were generated in
a healthy mouse model, they provide support for the continued evaluation
of pf-tPA for the treatment of pulmonary diseases, such as ARDS.},
issn = {1440-1681},
keywords = {B6C3F1 mice, haemorrhage, nebulization, pulmonary drug delivery, tissue
plasminogen activator},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1440-1681.2008.05011.x}
}
@ARTICLE{Strommenger2003,
author = {Strommenger, Birgit and Kettlitz, Christiane and Werner, Guido and
Witte, Wolfgang},
title = {Multiplex PCR Assay for Simultaneous Detection of Nine Clinically
Relevant Antibiotic Resistance Genes in Staphylococcus aureus},
journal = {J. Clin. Microbiol.},
year = {2003},
volume = {41},
pages = {4089--4094},
number = {9},
month = sep,
abstract = {In this study we describe a multiplex PCR assay for the detection
of nine clinically relevant antibiotic resistance genes of Staphylococcus
aureus. Conditions were optimized to amplify fragments of mecA (encoding
methicillin resistance), aacA-aphD (aminoglycoside resistance), tetK,
tetM (tetracycline resistance), erm(A), erm(C) (macrolide-lincosamide-streptogramin
B resistance), vat(A), vat(B), and vat(C) (streptogramin A resistance)
simultaneously in one PCR amplification. An additional primer pair
for the amplification of a fragment of the staphylococcal 16S rDNA
was included as a positive control. The multiplex PCR assay was evaluated
on 30 different S. aureus isolates, and the PCR results correlated
with the phenotypic antibiotic resistance data obtained by the broth
microdilution assay. The multiplex PCR assay offers a rapid, simple,
and accurate identification of antibiotic resistance profiles and
could be used in clinical diagnosis as well as for the surveillance
of the spread of antibiotic resistance determinants in epidemiological
studies.},
url = {http://jcm.asm.org/cgi/content/abstract/41/9/4089}
}
@ARTICLE{Strommenger2007,
author = {Strommenger, Birgit and Schmidt, Christiane and Werner, Guido and
Roessle-Lorch, Beate and Bachmann, Till T. and Witte, Wolfgang},
title = {DNA microarray for the detection of therapeutically relevant antibiotic
resistance determinants in clinical isolates of Staphylococcus aureus},
journal = {Molecular and Cellular Probes},
year = {2007},
volume = {21},
pages = {161--170},
number = {3},
month = jun,
abstract = {An oligonucleotide microarray was constructed for the rapid and sensitive
molecular detection of antibiotic resistance determinants in Staphylococcus
aureus. The array is equipped with oligonucleotide capture probes
for the detection of 10 clinically and therapeutically relevant antibiotic
resistance genes and -mutations (mecA, aacA-aphD, tetK, tetM, vat(A),
vat(B), vat(C), erm(A), erm(C), grlA-mutation) as well as several
control probes. A microarray concept was established including multiplexed
PCR amplification, DNA labeling, hybridization and data processing.
This concept was applied to clinical Staphylococcus aureus isolates
and results were concordant with those from standard genotypic and
phenotypic resistance testing. Our microarray concept offers rapid
and accurate identification of antibiotic resistance profiles. It
is easily expandable and thus can be adapted to changing clinical
and epidemiological requirements in clinical diagnosis as well as
in epidemiological studies.},
issn = {0890-8508},
keywords = {DNA microarray, Staphylococcus aureus, Antibiotic resistance, Diagnostic},
url = {http://www.sciencedirect.com/science/article/B6WNC-4M5238W-1/2/ec75dc43b73023dbde7e682fdbbfda91}
}
@ARTICLE{Stroncek2011,
author = {Stroncek, David F. and Xing, Lu and Chau, Quyen and Zia, Nausheen
and McKelvy, Alyce and Pracht, Leigh and Sabatino, Marianna and Jin,
Ping},
title = {Stability of cryopreserved white blood cells (WBCs) prepared for
donor WBC infusions},
journal = {Transfusion},
year = {2011},
volume = {51},
pages = {2647--2655},
number = {12},
abstract = {BACKGROUND: White blood cells (WBCs) collected from hematopoietic
stem cell transplant donors are often given to the recipient to speed
immune recovery or treat disease relapse. The postthaw recovery and
viability of cryopreserved donor WBCs, stored for as long as 7 years,
were assessed.STUDY DESIGN AND METHODS: Total nucleated cell (TNC)
cell recovery, CD3+ cell recovery, and TNC viability were measured
in 311 clinical donor WBC products: 168 products were unmanipulated
or minimally manipulated and 143 products were extensively manipulated.
An additional 45 products were selected because they were stored
for a longer duration; these were tested using both standard methods
and global transcriptional analysis. All products were cryopreserved
in 5% dimethyl sulfoxide (DMSO) plus 6% pentastarch and stored in
liquid nitrogen.RESULTS: The mean duration of storage of the 311
products was 143 days. Their TNC recovery was 92 ± 17%, CD3+ cell
recovery was 76 ± 19%, and the TNC viability was 84 ± 6%. Duration
of storage had no effect on TNC recovery, CD3+ cell recovery, or
TNC viability of the 311 products. The mean duration of storage of
the long-term stored products was 5.2 years; their TNC recovery (93 ± 14%)
and the TNC viability (78 ± 13%) did not differ from the 311 products,
but their CD3 cell recovery was greater (86 ± 22%; p = 0.0042).
Gene expression profiles of the long-term-stored products revealed
no differences due to storage duration.CONCLUSIONS: Donor WBC products
cryopreserved in 5% DMSO and 6% pentastarch can be stored in liquid
nitrogen for at least 7 years.},
doi = {10.1111/j.1537-2995.2011.03210.x},
issn = {1537-2995},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1537-2995.2011.03210.x}
}
@ARTICLE{Stroo2010,
author = {Stroo, Ingrid and Stokman, Geurt and Teske, Gwen J. D. and Raven,
Anje and Butter, Loes M. and Florquin, Sandrine and Leemans, Jaklien
C.},
title = {Chemokine expression in renal ischemia/reperfusion injury is most
profound during the reparative phase},
journal = {Int. Immunol.},
year = {2010},
volume = {22},
pages = {433--442},
number = {6},
month = jun,
abstract = {Chemokines are important players in the migration of leukocytes to
sites of injury and are also involved in angiogenesis, development
and wound healing. In this study, we performed microarray analyses
to identify chemokines that play a role during the inflammatory and
repair phase after renal ischemia/reperfusion (I/R) injury and investigated
the temporal relationship between chemokine expression, leukocyte
accumulation and renal damage/repair. C57Bl/6 mice were subjected
to unilateral ischemia for 45 min and sacrificed 3 h, 1 day and 7
days after reperfusion. From ischemic and contralateral kidney, RNA
was isolated and hybridized to a microarray. Microarray results were
validated with quantitative real-time reverse transcription-PCR (QRT-PCR)
on RNA from an independent experiment. (Immuno)histochemical analyses
were performed to determine renal damage/repair and influx of leukocytes.
Twenty out of 114 genes were up-regulated at one or more reperfusion
periods. All these genes were up-regulated 7 days after I/R. Up-regulated
genes included CC chemokines MCP-1 and TARC, CXC chemokines KC and
MIP-2{alpha}, chemokine receptors Ccr1 and Cx3cr1 and related genes
like matrix metalloproteinases. Microarray data of 1 and 7 days were
confirmed for 17 up-regulated genes by QRT-PCR. (Immuno)histochemical
analysis showed that the inflammatory and repair phase after renal
I/R injury take place after, respectively, 1 and 7 days. Interestingly,
chemokine expression was highest during the repair phase. In addition,
expression profiles showed a biphasic expression of all up-regulated
CXC chemokines coinciding with the early inflammatory and late repair
phase. In conclusion, we propose that temporal expression of chemokines
is a crucial factor in the regulation of renal I/R injury and repair.},
url = {http://intimm.oxfordjournals.org/cgi/content/abstract/22/6/433}
}
@ARTICLE{Strulovici-Barel2010,
author = {Strulovici-Barel, Yael and Omberg, Larsson and O'Mahony, Michael
and Gordon, Cynthia and Hollmann, Charleen and Tilley, Ann E and
Salit, Jacqueline and Mezey, Jason and Harvey, Ben-Gary and Crystal,
Ronald G},
title = {Threshold of Biologic Responses of the Small Airway Epithelium to
Low Levels of Tobacco Smoke},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2010},
pages = {201002-0294OC--},
month = aug,
abstract = {Rationale: Epidemiologic data demonstrate that individuals exposed
to low levels of tobacco smoke have decrements in lung function and
higher risk for lung disease compared to unexposed individuals. Although
this risk is small, low level tobacco smoke exposure is so widespread,
it is a significant public health concern. Objectives: To identify
biologic correlates of this risk, we hypothesized that, compared
to un-exposed individuals, individuals exposed to low levels of tobacco
smoke have biologic changes in the small airway epithelium, the site
of the first abnormalities associated with smoking. Methods: Small
airway epithelium was obtained by bronchoscopy from 121 individuals;
microarrays were used to assess genome wide gene expression; urine
nicotine and cotinine were used to categorize subjects as "nonsmokers,"
"active smokers," and "low exposure." Gene expression data was used
to determine the threshold and induction half maximal level (ID50)
of urine nicotine and cotinine at which the small airway epithelium
showed abnormal responses. Results: There was no threshold of urine
nicotine without a small airway epithelial response, and only slightly
above detectable urine cotinine threshold with a small airway epithelium
response. The ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml.
Conclusions: The small airway epithelium detects and responds to
low levels of tobacco smoke with transcriptome modifications. This
provides biologic correlates of epidemiologic studies linking low
level tobacco smoke exposure to lung health risk, identifies the
genes most sensitive to tobacco smoke and defines thresholds at which
the lung epithelium responds to low levels of tobacco smoke.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/201002-0294OCv1}
}
@ARTICLE{Strunk2004,
author = {Strunk, Karen E. and Amann, Vicky and Threadgill, David W.},
title = {Phenotypic Variation Resulting From a Deficiency of Epidermal Growth
Factor Receptor in Mice Is Caused by Extensive Genetic Heterogeneity
That Can Be Genetically and Molecularly Partitioned},
journal = {Genetics},
year = {2004},
volume = {167},
pages = {1821--1832},
number = {4},
month = aug,
abstract = {The timing of lethality caused by homozygosity for a null allele of
the epidermal growth factor receptor (Egfrtm1Mag) in mice is strongly
dependent on genetic background. Initial attempts to genetically
map background modifiers using Swiss-derived, outbred CD-1 mice were
unsuccessful. To investigate the genetic architecture contributing
to survival of Egfrtm1Mag homozygous embryos, the genetic variability
segregating within the outbred population was partitioned by surveying
viability of Egfrtm1Mag mutants using intercrosses between 129S6/SvEvTAC-Egfrtm1Mag
and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS,
ICR/HaRos, NOD/LtJ, NON/LtJ, SJL/J, and SWR/J. The observations showed
that these strains support varying levels of survival of Egfrtm1Mag
homozygous embryos, suggesting that genetic heterogeneity within
the CD-1 stock contributed to the original lack of Egfrtm1Mag modifier
detection. Similar to the Swiss-derived intercrosses, nine congenic
strains, derived from 129S6/SvEvTAC, AKR/J, APN, BALB/cJ, BTBR-T+
tf/tf, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ inbred backgrounds,
also supported varying levels of survival of Egfrtm1Mag mutants.
By intercrossing the congenic lines to create hybrid F1 embryos,
different genetic backgrounds were found to have complementary modifiers.
Analysis of the congenic lines argues against heterosis of outbred
backgrounds contributing to Egfrtm1Mag phenotypic variability. A
detailed analysis of the crosses suggests that modifiers function
at three distinct stages of development. One class of modifiers supports
survival of Egfrtm1Mag homozygous embryos to mid-gestation, another
class supports development through the mid-gestation transition from
yolk-sac to placental-derived nutrient sources, and a third class
supports survival through later stages of gestation. Data from microarray
analysis using RNA from wild-type and Egfrtm1Mag mutant placentas
support the existence of extensive genetic heterogeneity and suggest
that it can be molecularly partitioned. This method should be generally
useful to partition heterogeneity contributing to other complex traits.},
url = {http://www.genetics.org/cgi/content/abstract/167/4/1821}
}
@ARTICLE{Strunnikova2010,
author = {Strunnikova, N.V. and Maminishkis, A. and Barb, J.J. and Wang, F.
and Zhi, C. and Sergeev, Y. and Chen, W. and Edwards, A.O. and Stambolian,
D. and Abecasis, G. and Swaroop, A. and Munson, P.J. and Miller,
S.S.},
title = {Transcriptome analysis and molecular signature of human retinal pigment
epithelium},
journal = {Hum. Mol. Genet.},
year = {2010},
volume = {19},
pages = {2468--2486},
number = {12},
month = jun,
abstract = {Retinal pigment epithelium (RPE) is a polarized cell layer critical
for photoreceptor function and survival. The unique physiology and
relationship to the photoreceptors make the RPE a critical determinant
of human vision. Therefore, we performed a global expression profiling
of native and cultured human fetal and adult RPE and determined a
set of highly expressed signature' genes by comparing the observed
RPE gene profiles to the Novartis expression database (SymAtlas:
http://wombat.gnf.org/index.html) of 78 tissues. Using stringent
selection criteria of at least 10-fold higher expression in three
distinct preparations, we identified 154 RPE signature genes, which
were validated by qRT-PCR analysis in RPE and in an independent set
of 11 tissues. Several of the highly expressed signature genes encode
proteins involved in visual cycle, melanogenesis and cell adhesion
and Gene ontology analysis enabled the assignment of RPE signature
genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20)
or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes
were associated with known ophthalmic diseases, and 25 others were
mapped to regions of disease loci. An evaluation of the RPE signature
genes in a recently completed AMD genomewide association (GWA) data
set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes
may have potential roles in AMD pathogenesis and deserve further
examination. We propose that RPE signature genes are excellent candidates
for retinal diseases and for physiological investigations (e.g. dopachrome
tautomerase in melanogenesis). The RPE signature gene set should
allow the validation of RPE-like cells derived from human embryonic
or induced pluripotent stem cells for cell-based therapies of degenerative
retinal diseases.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/19/12/2468}
}
@ARTICLE{Struve2009,
author = {Struve, Melanie F. and Gaido, Kevin W. and Hensley, Janan B. and
Lehmann, Kim P. and Ross, Susan M. and Sochaski, Mark A. and Willson,
Gabrielle A. and Dorman, David C.},
title = {Reproductive toxicity and pharmacokinetics of di-n-butyl phthalate
(DBP) following dietary exposure of pregnant rats},
journal = {Birth Defects Research Part B: Developmental and Reproductive Toxicology},
year = {2009},
volume = {86},
pages = {345--354},
number = {4},
abstract = {Abstract 10.1002/bdrb.20199.abs Most rodent developmental toxicity
studies of dibutylphthalate (DBP) have relied on bolus gavage dosing.
This study characterized the developmental toxicity of dietary DBP.
Pregnant CD rats were given nominal doses of 0, 100, or 500 mg
DBP/kg/day in diet (actual intake 0, 112, and 582 mg/kg/day) from
gestational day (GD) 12 through the morning of GD 19. Rats were killed
4 or 24 hr thereafter. DBP dietary exposure resulted in significant
dose-dependent reductions in testicular mRNA concentration of scavenger
receptor class B, member 1; steroidogenic acute regulatory protein;
cytochrome P450, family 11, subfamily a, polypeptide 1; and cytochrome
P450 family 17, subfamily a, polypeptide 1. These effects were most
pronounced 4 hr after the end of exposure. Testicular testosterone
was reduced 24 hr post-exposure in both DBP dose groups and 4 hr
after termination of the 500-mg DBP/kg/day exposure. Maternal exposure
to 500 mg DBP/kg/day induced a significant reduction in male offspring's
anogenital distance indicating in utero disruption of androgen function.
Leydig cell aggregates, increased cord diameters, and multinucleated
gonocytes were present in DBP-treated rats. Monobutyl phthalate,
the developmentally toxic metabolite of DBP, and its glucuronide
conjugate were found in maternal and fetal plasma, amniotic fluid,
and maternal urine. Our results, when compared to previously conducted
gavage studies, indicate that approximately equal doses of oral DBP
exposure of pregnant rats, from diet or gavage, result in similar
responses in male offspring. Birth Defects Res (Part B), 86:345–354,
2009. © 2009 Wiley-Liss, Inc.},
issn = {1542-9741},
keywords = {anti-androgen, endocrine disruptor, phthalate},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bdrb.20199}
}
@ARTICLE{StrA¶mberg2008,
author = {Strömberg, Sara and Björklund, Marcus Gry and Asplund, Anna and
Rimini, Rebecca and Lundeberg, Joakim and Nilsson, Peter and Pontén,
Fredrik and Olsson, Mats J.},
title = {Transcriptional profiling of melanocytes from patients with vitiligo
vulgaris},
journal = {Pigment Cell \& Melanoma Research},
year = {2008},
volume = {21},
pages = {162--171},
number = {2},
abstract = {Summary Vitiligo is a complex, polygenic disorder characterized by
patchy loss of skin pigmentation due to abnormal melanocyte function.
Both genetic and environmental etiological factors have been proposed
for vitiligo and lack of molecular markers renders difficulties to
predict development and progression of the disease. Identification
of dysregulated genes has the potential to unravel biological pathways
involved in vitiligo pathogenesis, facilitating discovery of potential
biomarkers and novel therapeutic approaches. In this study, we characterized
the transcriptional profile of melanocytes from vitiligo patients.
Oligonucleotide microarrays containing ∼16 000 unique genes were
used to analyse mRNA expression in melanocytes from vitiligo patients
and age-matched healthy controls. In total, 859 genes were identified
as differentially expressed. A substantial number of these genes
were involved in (i) melanocyte development, (ii) intracellular processing
and trafficking of tyrosinase gene family proteins, (iii) packing
and transportation of melanosomes, (iv) cell adhesion and (v) antigen
processing and presentation. In conclusion, our results show a significantly
different transcription profile in melanocytes from vitiligo patients
compared with controls. Several genes of potential importance for
the pathogenesis and development of vitiligo were identified. Our
data indicate that autoimmunity involving melanocytes may be a secondary
event in vitiligo patients caused by abnormal melanocyte function.},
issn = {1755-148X},
keywords = {vitiligo, melanocytes, microarray, transcription profiling, tyrosinase
gene family, melanosome transport, cell adhesion, antigen presentation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-148X.2007.00429.x}
}
@ARTICLE{StrA¶mberg2007,
author = {Strömberg, Sara and Björklund, Marcus Gry and Asplund, Caroline
and Sköllermo, Anna and Persson, Anja and Wester, Kenneth and Kampf,
Caroline and Nilsson, Peter and Andersson, Ann-Catrin and Uhlen,
Mathias and Kononen, Juha and Ponten, Fredrik and Asplund, Anna},
title = {A high-throughput strategy for protein profiling in cell microarrays
using automated image analysis},
journal = {Proteomics},
year = {2007},
volume = {7},
pages = {2142--2150},
number = {13},
abstract = {Abstract Advances in antibody production render a growing supply of
affinity reagents for immunohistochemistry (IHC), and tissue microarray
(TMA) technologies facilitate simultaneous analysis of protein expression
in a multitude of tissues. However, collecting validated IHC data
remains a bottleneck problem, as the standard method is manual microscopical
analysis. Here we present a high-throughput strategy combining IHC
on a recently developed cell microarray with a novel, automated image-analysis
application (TMAx). The software was evaluated on 200 digital images
of IHC-stained cell spots, by comparing TMAx annotation with manual
annotation performed by seven human experts. A high concordance between
automated and manual annotation of staining intensity and fraction
of IHC-positive cells was found. In a limited study, we also investigated
the possibility to assess the correlation between mRNA and protein
levels, by using TMAx output results for relative protein quantification
and quantitative real-time PCR for the quantification of corresponding
transcript levels. In conclusion, automated analysis of immunohistochemically
stained in vitro-cultured cells in a microarray format can be used
for high-throughput protein profiling, and extraction of RNA from
the same cell lines provides a basis for comparing transcription
and protein expression on a global scale.},
issn = {1615-9861},
keywords = {Antibody proteomics, Automated image analysis, Cell line, Immunohistochemistry,
Tissue microarray},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200700199}
}
@ARTICLE{Struebing2010,
author = {Strübing, Uta and Lucius, Richard and Hoerauf, Achim and Pfarr, Kenneth
M.},
title = {Mitochondrial genes for heme-dependent respiratory chain complexes
are up-regulated after depletion of Wolbachia from filarial nematodes},
journal = {International Journal for Parasitology},
year = {2010},
volume = {40},
pages = {1193--1202},
number = {10},
month = aug,
abstract = {The filarial nematodes Brugia malayi, Wuchereria bancrofti and Onchocerca
volvulus cause elephantiasis or dermatitis and blindness resulting
in severe morbidity. Annually, 1.3 billion people are at risk of
infection. Targeting the essential Wolbachia endobacteria of filarial
nematodes with doxycycline has proven to be an effective therapy
resulting in a block in embryogenesis, worm development and macrofilaricidal
effects. However, doxycycline is contraindicated for a large portion
of the at risk population. To identify new targets for anti-wolbachial
therapy, understanding the molecular basis of the Wolbachia-filaria
symbiosis is required. Using the B. malayi microarray we identified
differentially expressed genes in the rodent filaria Litomosoides
sigmodontis after depletion of Wolbachia which might have a role
in symbiosis. The microarray data were filtered for regulated genes
with a false discovery rate <5% and a [greater-or-equal, slanted]2-fold-change.
Most of the genes were differentially expressed at day 36 of tetracycline
treatment, when 99.8% of Wolbachia were depleted. Several classes
of genes were affected, including genes for translation, transcription,
folding/sorting of proteins, motility, structure and metabolic and
signalling pathways. Quantitative PCR validated 60% of the genes
found to be regulated in the microarray. A nuclear encoded heme-binding
protein of the globin family was up-regulated upon loss of Wolbachia.
Interestingly, mitochondrial encoded subunits of respiratory chain
complexes containing heme and riboflavin were also up-regulated.
No change in the expression of these genes was seen in tetracycline
treated Wolbachia-free Acanthocheilonema viteae. As Wolbachia synthesise
heme and filaria do not, we hypothesise that without the endosymbionts
no functional heme-containing enzymes can be formed, leading to loss
of energy metabolism which then results in up-regulation of the mitochondrial
encoded subunits in an attempt to correct the deviation from homeostasis.
Our results support targeting the Wolbachia heme synthesis pathway
for the discovery of new anti-filarial drugs.},
booktitle = {ICOPA XII, ICOPA XII},
issn = {0020-7519},
keywords = {Filariasis, Litomosoides sigmodontis, Wolbachia, Symbiosis, Microarray,
Heme, Tetracycline, Mitochondria},
url = {http://www.sciencedirect.com/science/article/B6T7F-4YRPDXJ-1/2/020d379d522b995647d408dddb2fcaff}
}
@ARTICLE{Stuart2009,
author = {Stuart, Charles A. and Howell, Mary E. A. and Zhang, Yi and Yin,
Deling},
title = {Insulin-Stimulated Translocation of Glucose Transporter (GLUT) 12
Parallels That of GLUT4 in Normal Muscle},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {3535--3542},
number = {9},
month = sep,
abstract = {Context: GLUT4 is the predominant glucose transporter isoform expressed
in fat and muscle. In GLUT4 null mice, insulin-stimulated glucose
uptake into muscle was diminished but not eliminated, suggesting
that another insulin-sensitive system was present. Objective: This
study was intended to determine whether insulin caused GLUT12 translocation
in muscle. Design: Six normal volunteers had muscle biopsies before
and after euglycemic insulin infusions. Setting: Infusions and biopsies
were performed in an outpatient clinic. Participants: Subjects were
nonobese, young adults with no family history of diabetes. Main Outcome
Measures: GLUT12, GLUT4, and GLUT1 proteins were quantified in muscle
biopsy fractions. Cultured myoblasts were used to determine whether
GLUT12 translocation was phosphatidyl inositol-3 kinase (PI3-K)-dependent.
Intervention. Insulin was infused at 40 mU/m2 {middle dot} min for
3 h. Results: In human muscle, insulin caused a shift of a portion
of GLUT12 from intracellular low-density microsomes to the plasma
membrane (PM) fraction (17% in PM at baseline, 38% in PM after insulin).
Insulin increased GLUT4 in PM from 13 to 42%. GLUT1 was predominantly
in the PM fractions at baseline and did not change significantly
after insulin. L6 myoblasts in culture also expressed and translocated
GLUT12 in response to insulin, but inhibiting PI3-K prevented the
translocation of GLUT12 and GLUT4. Conclusions: Insulin causes GLUT12
to translocate from an intracellular location to the plasma membrane
in normal human skeletal muscle. Translocation of GLUT12 in cultured
myoblasts was dependent on activation of PI3-K. GLUT12 may have evolutionarily
preceded GLUT4 and now provides redundancy to the dominant GLUT4
system in muscle.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/9/3535}
}
@ARTICLE{Stuart2009a,
author = {Stuart, Gregory R. and Humble, Margaret M. and Strand, Micheline
K. and Copeland, William C.},
title = {Transcriptional response to mitochondrial NADH kinase deficiency
in Saccharomyces cerevisiae},
journal = {Mitochondrion},
year = {2009},
volume = {9},
pages = {211--221},
number = {3},
month = jun,
abstract = {Yeast cells lacking the mitochondrial NADH kinase encoded by POS5
display increased sensitivity to hydrogen peroxide, a slow-growth
phenotype, reduced mitochondrial function and increased levels of
mitochondrial protein oxidation and mtDNA mutations. Here we examined
gene expression in pos5[Delta] cells, comparing these data to those
from cells containing deletions of superoxide dismutase-encoding
genes SOD1 or SOD2. Surprisingly, stress-response genes were down-regulated
in pos5[Delta], sod1[Delta] and sod2[Delta] cells, implying that
cells infer stress levels from mitochondrial activity rather than
sensing reactive oxygen species directly. Additionally, pos5[Delta],
but not sod1 or sod2, cells displayed an anaerobic expression profile,
indicating a defect in oxygen sensing that is specific to pos5, and
is not a general stress-response. Finally, the pos5[Delta] expression
profile is quite similar to the hap1[Delta] expression profile previously
reported, which may indicate a shared mechanism.},
issn = {1567-7249},
keywords = {Cytoscape, Microarray, Mitochondria, NADH kinase, Oxidative stress,
POS5},
url = {http://www.sciencedirect.com/science/article/B6W8G-4VR247Y-1/2/4f3ecf7293fcefb9483aecaff528865f}
}
@ARTICLE{Stuart2004,
author = {Stuart, Robert O. and Wachsman, William and Berry, Charles C. and
Wang-Rodriguez, Jessica and Wasserman, Linda and Klacansky, Igor
and Masys, Dan and Arden, Karen and Goodison, Steven and McClelland,
Michael and Wang, Yipeng and Sawyers, Anne and Kalcheva, Iveta and
Tarin, David and Mercola, Dan},
title = {In silico dissection of cell-type-associated patterns of gene expression
in prostate cancer},
journal = {PNAS},
year = {2004},
volume = {101},
pages = {615--620},
number = {2},
month = jan,
abstract = {Prostate tumors are complex entities composed of malignant cells mixed
and interacting with nonmalignant cells. However, molecular analyses
by standard gene expression profiling are limited because spatial
information and nontumor cell types are lost in sample preparation.
We scored 88 prostate specimens for relative content of tumor, benign
hyperplastic epithelium, stroma, and dilated cystic glands. The proportions
of these cell types were then linked in silico to gene expression
levels determined by microarray analysis, revealing unique cell-specific
profiles. Gene expression differences for malignant and nonmalignant
epithelial cells (tumor versus benign hyperplastic epithelium) could
be identified without being confounded by contributions from stroma
that dominate many samples or sacrificing possible paracrine influences.
Cell-specific expression of selected genes was validated by immunohistochemistry
and quantitative PCR. The results provide patterns of gene expression
for these three lineages with relevance to pathogenetic, diagnostic,
and therapeutic considerations.},
url = {http://www.pnas.org/cgi/content/abstract/101/2/615}
}
@ARTICLE{Stuckenholz2009,
author = {Stuckenholz, Carsten and Lu, Lili and Thakur, Prakash and Kaminski,
Naftali and Bahary, Nathan},
title = {FACS-Assisted Microarray Profiling Implicates Novel Genes and Pathways
in Zebrafish Gastrointestinal Tract Development},
journal = {Gastroenterology},
year = {2009},
volume = {137},
pages = {1321--1332},
number = {4},
month = oct,
abstract = {Background & Aims The zebrafish Danio rerio is an excellent model
system for mammalian gastrointestinal development. To identify differentially
regulated genes important in gastrointestinal organogenesis, we profiled
the transcriptome of the zebrafish developing gastrointestinal tract.Methods
Embryos from a transgenic zebrafish line expressing green fluorescent
protein (GFP) in the developing intestine, liver, and pancreas were
dissociated at 4 developmental time points, their cells sorted based
on GFP expression with fluorescence-activated cell sorting (FACS),
and analyzed with microarrays. To improve our analysis, we annotated
the Affymetrix Zebrafish GeneChip with human orthologs.Results Transcriptional
profiling showed significant differences between GFP+ and GFP- cells.
Up-regulated genes and pathways were consistent with mammalian gastrointestinal
development, such as hepatic nuclear factor gene networks and cancer.
We implicate the phosphatidylinositol 3 kinase (PI3K) pathway and
show that inhibition with LY294002 causes gastrointestinal defects
in zebrafish. We identified novel genes, such as the microRNAs miR-217
and miR-122, the tight junction protein claudin c, the gene fam136a,
and a zebrafish tetraspanin. Novel pathways include genes containing
a putative transcription factor binding sequence, GGAANCGGAANY, and
a nucleolar gene network. The zebrafish microarrays also identify
a set of 32 genes that may mediate the effects of gain of chromosome
arm 8q in human colon, liver, and pancreatic cancers.Conclusions
We successfully combine FACS and microarray profiling to follow organogenesis
throughout development. These experiments identify novel genes and
pathways that probably play a role in mammalian gastrointestinal
development and are potential targets for therapeutic intervention
in the management of gastrointestinal disease and cancer.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4WMDHG8-1/2/802b8323a1365c11dc64962085bf6ec1}
}
@ARTICLE{Stuckey2011,
author = {Stuckey, Ashley and Fischer, Andrew and Miller, Daniel and Hillenmeyer,
Sara and Kim, Kyu and Ritz, Anna and Singh, Rakesh and Raphael, Benjamin
and Brard, Laurent and Brodsky, Alexander},
title = {Integrated genomics of ovarian xenograft tumor progression and chemotherapy
response},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {308},
number = {1},
abstract = {BACKGROUND:Ovarian cancer is the most deadly gynecological cancer
with a very poor prognosis. Xenograft mouse models have proven to
be one very useful tool in testing candidate therapeutic agents and
gene function in vivo. In this study we identify genes and gene networks
important for the efficacy of a pre-clinical anti-tumor therapeutic,
MT19c.METHODS:In order to understand how ovarian xenograft tumors
may be growing and responding to anti-tumor therapeutics, we used
genome-wide mRNA expression and DNA copy number measurements to identify
key genes and pathways that may be critical for SKOV-3 xenograft
tumor progression. We compared SKOV-3 xenografts treated with the
ergocalciferol derived, MT19c, to untreated tumors collected at multiple
time points. Cell viability assays were used to test the function
of the PPARgamma agonist, Rosiglitazone, on SKOV-3 cell growth.RESULTS:These
data indicate that a number of known survival and growth pathways
including Notch signaling and general apoptosis factors are differentially
expressed in treated vs. untreated xenografts. As tumors grow, cell
cycle and DNA replication genes show increased expression, consistent
with faster growth. The steroid nuclear receptor, PPARgamma, was
significantly up-regulated in MT19c treated xenografts. Surprisingly,
stimulation of PPARgamma with Rosiglitazone reduced the efficacy
of MT19c and cisplatin suggesting that PPARgamma is regulating a
survival pathway in SKOV-3 cells. To identify which genes may be
important for tumor growth and treatment response, we observed that
MT19c down-regulates some high copy number genes and stimulates expression
of some low copy number genes suggesting that these genes are particularly
important for SKOV-3 xenograft growth and survival.CONCLUSIONS:We
have characterized the time dependent responses of ovarian xenograft
tumors to the vitamin D analog, MT19c. Our results suggest that PPARgamma
promotes survival for some ovarian tumor cells. We propose that a
combination of regulated expression and copy number can identify
genes that are likely important for chemotherapy response. Our findings
suggest a new approach to identify candidate genes that are critical
for anti-tumor therapy.},
doi = {10.1186/1471-2407-11-308},
issn = {1471-2407},
pubmedid = {21781307},
url = {http://www.biomedcentral.com/1471-2407/11/308}
}
@ARTICLE{Stucky2011,
author = {Stucky, Nicholas L. and Gregory, Eugene and Winter, Michelle K. and
He, Yong-Yue and Hamilton, Eric S. and McCarson, Kenneth E. and Berman,
Nancy E.J.},
title = {Sex Differences in Behavior and Expression of CGRP-Related Genes
in a Rodent Model of Chronic Migraine},
journal = {Headache: The Journal of Head and Face Pain},
year = {2011},
volume = {51},
pages = {674--692},
number = {5},
abstract = {(Headache 2011;51:674-692)Objective.— The objectives of this study
were to develop a preclinical rodent model that produces migraine-like
behaviors based on International Headache Society diagnostic criteria,
to determine whether sex differences are present, and to determine
whether expression of calcitonin gene-related peptide (CGRP) and
the genes encoding its receptor in trigeminal ganglion or medulla
correlates with those behaviors.Background.— Few animal studies
of migraine have tested behaviors associated with migraine diagnostic
criteria. In this study, changes in activity and in mechanical sensitivity
of facial regions following application of inflammatory soup (IS)
or vehicle (phosphate-buffered saline [PBS]) to the dura were measured
to model changes in routine activity and allodynia. CGRP, an important
mediator of migraine pathogenesis, and the 3 components of its receptor,
calcitonin-like receptor (CLR), receptor activity-modifying protein
1 (RAMP1), and receptor component protein (RCP) mRNAs were quantified
in the trigeminal ganglion and medulla to identify baseline sex differences
and changes associated with application of IS or PBS to the dura.Methods.—
Male and female Sprague-Dawley rats were implanted with a dural cannula.
Groups of rats were treated with 10 or 20 µL volumes of IS or PBS.
Baseline behavioral testing was conducted prior to surgery and again
at 7 days postsurgery, and dural application of IS or PBS was performed
repeatedly for a total of 8 applications. Locomotor activity was
assessed using force plate actimetry during and following application
to provide information on distance traveled, bouts of low mobility,
spatial confinement, and focused energy. Periorbital and perimasseter
sensory testing was performed 20 minutes post-application to measure
allodynia. The rats were sacrificed 30 minutes following the final
dural treatment, tissue was dissected and total RNAs were isolated
from ipsilateral trigeminal ganglia and ipsilateral medulla. Quantitative
real-time polymerase chain reactions were used to measure the expression
of amplified constructs using gene-specific primers for CGRP, RAMP1,
CLR, and RCP.Results.— Both males and females showed behavioral
effects of IS application, but there were pronounced sex differences.
Females showed effects at the lower dose, and activity changes were
present for a longer duration, but males required fewer applications
of IS to exhibit behavioral changes. Females showed increased withdrawal
responses for periorbital and perimasseter mechanical testing (10 µL
IS groups), and males showed increased perimasseter withdrawal responses
(20 µL IS group). In the trigeminal ganglion, there were no baseline
sex differences in CGRP-encoding mRNA, but females had lower baseline
expression of RAMP1, CLR, and RCP-encoding mRNAs. In the medulla,
females had higher baseline levels of CGRP-encoding mRNAs and lower
baseline levels of RAMP1, CLR, and RCP-encoding mRNAs than males.
Both IS and PBS increased expression of mRNAs encoding CGRP, RAMP1,
RCP, and CLR in the trigeminal ganglion in males, but in females,
only CLR and RCP were increased. In the medulla both IS and PBS increased
expression of CGRP, CLR in males and CLR and RCP in females. Thus,
expression of CGRP-related genes did not mirror the behavioral differences
between IS and PBS groups. Instead, CGRP-related genes were upregulated
by both IS and PBS applications.Conclusions.— This study demonstrates
significant changes in locomotor activity and facial allodynia associated
with application of IS to the dura as well as significant sex differences,
demonstrating that International Headache Society diagnostic criteria
can be used to design a rodent behavioral model of migraine. In addition,
there were prominent baseline sex differences in expression of CGRP
and its receptor in both the trigeminal ganglion and medulla, but
the majority of changes in expression of CGRP and its receptor were
present in both the IS and PBS treated rats. This suggests that the
CGRP pathway responds to changes in intracranial pressure or meningeal
stretch, while migraine-like behaviors occur after meningeal inflammation.},
doi = {10.1111/j.1526-4610.2011.01882.x},
issn = {1526-4610},
keywords = {chronic migraine, inflammatory soup, facial allodynia, locomotor activity,
sex difference, calcitonin gene-related peptide},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1526-4610.2011.01882.x}
}
@ARTICLE{Stuiver2011,
author = {Stuiver, Marchel and Lainez, Sergio and Will, Constanze and Terryn,
Sara and Günzel, Dorothee and Debaix, Huguette and Sommer, Kerstin
and Kopplin, Kathrin and Thumfart, Julia and Kampik, Nicole B. and
Querfeld, Uwe and Willnow, Thomas E. and Nemec, Vladimír and Wagner,
Carsten A. and Hoenderop, Joost G. and Devuyst, Olivier and Knoers,
Nine V.A.M. and Bindels, René J. and Meij, Iwan C. and Müller, Dominik},
title = {CNNM2, Encoding a Basolateral Protein Required for Renal Mg2+ Handling,
Is Mutated in Dominant Hypomagnesemia},
journal = {The American Journal of Human Genetics},
year = {2011},
volume = {88},
pages = {333--343},
number = {3},
month = mar,
abstract = {Familial hypomagnesemia is a rare human disorder caused by renal or
intestinal magnesium (Mg2+) wasting, which may lead to symptoms of
Mg2+ depletion such as tetany, seizures, and cardiac arrhythmias.
Our knowledge of the physiology of Mg2+ (re)absorption, particularly
the luminal uptake of Mg2+ along the nephron, has benefitted from
positional cloning approaches in families with Mg2+ reabsorption
disorders; however, basolateral Mg2+ transport and its regulation
are still poorly understood. Here, by using a candidate screening
approach, we identified CNNM2 as a gene involved in renal Mg2+ handling
in patients of two unrelated families with unexplained dominant hypomagnesemia.
In the kidney, CNNM2 was predominantly found along the basolateral
membrane of distal tubular segments involved in Mg2+ reabsorption.
The basolateral localization of endogenous and recombinant CNNM2
was confirmed in epithelial kidney cell lines. Electrophysiological
analysis showed that CNNM2 mediated Mg2+-sensitive Na+ currents that
were significantly diminished in mutant protein and were blocked
by increased extracellular Mg2+ concentrations. Our data support
the findings of a recent genome-wide association study showing the
CNNM2 locus to be associated with serum Mg2+ concentrations. The
mutations found in CNNM2, its observed sensitivity to extracellular
Mg2+, and its basolateral localization signify a critical role for
CNNM2 in epithelial Mg2+ transport.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S000292971100053X}
}
@ARTICLE{Stushnoff2010,
author = {Stushnoff, Cecil and Ducreux, Laurence J. M. and Hancock, Robert
D. and Hedley, Pete E. and Holm, David G. and McDougall, Gordon J.
and McNicol, James W. and Morris, Jenny and Morris, Wayne L. and
Sungurtas, Julie A. and Verrall, Susan R. and Zuber, Tatiana and
Taylor, Mark A.},
title = {Flavonoid profiling and transcriptome analysis reveals new gene-metabolite
correlations in tubers of Solanum tuberosum L.},
journal = {J. Exp. Bot.},
year = {2010},
volume = {61},
pages = {1225--1238},
number = {4},
month = mar,
abstract = {Anthocyanin content of potato tubers is a trait that is attracting
increasing attention as the potential nutritional benefits of this
class of compound become apparent. However, our understanding of
potato tuber anthocyanin accumulation is not complete. The aim of
this study was to use a potato microarray to investigate gene expression
patterns associated with the accumulation of purple tuber anthocyanins.
The advanced potato selections, CO97216-3P/PW and CO97227-2P/PW,
developed by conventional breeding procedures, produced tubers with
incomplete expression of tuber flesh pigmentation. This feature permits
sampling pigmented and non-pigmented tissues from the same tubers,
in essence, isolating the factors responsible for pigmentation from
confounding genetic, environmental, and developmental effects. An
examination of the transcriptome, coupled with metabolite data from
purple pigmented sectors and from non-pigmented sectors of the same
tuber, was undertaken to identify these genes whose expression correlated
with elevated or altered polyphenol composition. Combined with a
similar study using eight other conventional cultivars and advanced
selections with different pigmentation, it was possible to produce
a refined list of only 27 genes that were consistently differentially
expressed in purple tuber tissues compared with white. Within this
list are several new candidate genes that are likely to impact on
tuber anthocyanin accumulation, including a gene encoding a novel
single domain MYB transcription factor.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/61/4/1225}
}
@ARTICLE{Stygar2007,
author = {Stygar, Denis and Masironi, Britt and Eriksson, Hakan and Sahlin,
Lena},
title = {Studies on estrogen receptor (ER) {alpha} and {beta} responses on
gene regulation in peripheral blood leukocytes in vivo using selective
ER agonists},
journal = {J. Endocrinol.},
year = {2007},
volume = {194},
pages = {101--119},
number = {1},
month = jul,
abstract = {Major reproductive events such as menstruation, ovulation, implantation,
and cervical ripening are characterized by an increased number of
invading leukocytes in the tissues. Sex steroid hormones, particularly
estrogens, play an important role in these dynamic changes in the
female reproductive tract. Estrogens have also been implicated in
the pathogenesis of many common pathological conditions associated
with leukocyte infiltration and immunological dysfunction, such as
auto-immune diseases and atherosclerosis. Although the two estrogen
receptor (ER) subtypes, ER{alpha} and ER{beta}, have been found in
different leukocyte populations in tissues and in peripheral blood,
there is still very little known about functional activity and importance
of ERs in blood cells. To elucidate the different roles for ER{alpha}
and ER{beta} in peripheral blood leukocytes, we used microarray gene
expression profiling of rat peripheral blood leukocytes subjected
to in vivo treatment with estradiol (E2), the selective ER{alpha}
agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT),
and the selective ER{beta} agonist 2,3-bis(4-hydroxyphenyl)-propionitrile
(DPN). We report the identification of genes that were commonly regulated
by E2, PPT, and DPN, and genes that were regulated either by the
ER{alpha} or ER{beta} agonist. Further confirmatory analyses of the
selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin
B are also presented. These results were then compared with those
from the uterine tissue of the same animals. Our study demonstrates
that peripheral blood leukocytes are responsive to estrogens. E2
and selective ER{alpha} and ER{beta} agonists regulate a number of
genes that may contribute to inflammation and remodeling of the extracellular
matrix.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/194/1/101}
}
@ARTICLE{Stylianou2008,
author = {Stylianou, Ioannis M. and Affourtit, Jason P. and Shockley, Keith
R. and Wilpan, Robert Y. and Abdi, Fadi A. and Bhardwaj, Sanjeev
and Rollins, Jarod and Churchill, Gary A and Paigen, Beverly},
title = {Applying Gene Expression, Proteomics and Single-Nucleotide Polymorphism
Analysis for Complex Trait Gene Identification},
journal = {Genetics},
year = {2008},
volume = {178},
pages = {1795--1805},
number = {3},
month = mar,
abstract = {Previous quantitative trait locus (QTL) analysis of an intercross
involving the inbred mouse strains NZB/BlNJ and SM/J revealed QTL
for a variety of complex traits. Many QTL have large intervals containing
hundreds of genes, and methods are needed to rapidly sort through
these genes for probable candidates. We chose nine QTL: the three
most significant for high-density lipoprotein (HDL) cholesterol,
gallstone formation, and obesity. We searched for candidate genes
using three different approaches: mRNA microarray gene expression
technology to assess >45,000 transcripts, publicly available SNPs
to locate genes that are not identical by descent and that contain
nonsynonymous coding differences, and a mass-spectrometry-based proteomics
technology to interrogate nearly 1000 proteins for differential expression
in the liver of the two parental inbred strains. This systematic
approach reduced the number of candidate genes within each QTL from
hundreds to a manageable list. Each of the three approaches selected
candidates that the other two approaches missed. For example, candidate
genes such as Apoa2 and Acads had differential protein levels although
the mRNA levels were similar. We conclude that all three approaches
are important and that focusing on a single approach such as mRNA
expression may fail to identify a QTL gene.},
url = {http://www.genetics.org/cgi/content/abstract/178/3/1795}
}
@ARTICLE{Stylianou2008a,
author = {Stylianou, Ioannis M. and Langley, Sarah R. and Walsh, Kenneth and
Chen, Yuan and Revenu, Celine and Paigen, Beverly},
title = {Differences in DBA/1J and DBA/2J reveal lipid QTL genes},
journal = {J. Lipid Res.},
year = {2008},
volume = {49},
pages = {2402--2413},
number = {11},
month = nov,
abstract = {Recent advances in mouse genomics have revealed considerable variation
in the form of single-nucleotide polymorphisms (SNPs) among common
inbred strains. This has made it possible to characterize closely
related strains and to identify genes that differ; such genes may
be causal for quantitative phenotypes. The mouse strains DBA/1J and
DBA/2J differ by just 5.6% at the SNP level. These strains exhibit
differences in a number of metabolic and lipid phenotypes, such as
plasma levels of triglycerides (TGs) and HDL. A cross between these
strains revealed multiple quantitative trait loci (QTLs) in 294 progeny.
We identified significant TG QTLs on chromosomes (Chrs) 1, 2, 3,
4, 8, 9, 10, 11, 12, 13, 14, 16, and 19, and significant HDL QTLs
on Chrs 3, 9, and 16. Some QTLs mapped to chromosomes with limited
variability between the two strains, thus facilitating the identification
of candidate genes. We suggest that Tshr is the QTL gene for Chr
12 TG and HDL levels and that Ihh may account for the TG QTL on Chr
1. This cross highlights the advantage of crossing closely related
strains for subsequent identification of QTL genes.},
url = {http://www.jlr.org/cgi/content/abstract/49/11/2402}
}
@ARTICLE{Staalberg2006,
author = {Stålberg, Peter and Santesson, Mårten and Ekeblad, Sara and Lejonklou,
Margareta Halin and Skogseid, Britt},
title = {Recognizing genes differentially regulated in vitro by the multiple
endocrine neoplasia type 1 (MEN1) gene, using RNA interference and
oligonucleotide microarrays},
journal = {Surgery},
year = {2006},
volume = {140},
pages = {921--931},
number = {6},
month = dec,
abstract = {Background Data on downstream effects of MEN1 gene inactivation is
scarce. In an effort to identify genes regulated by MEN1, we designed
a silencing experiment in a human endocrine pancreatic tumor cell
line (BON1).Methods By using RNA interference, MEN1 mRNA expression
was knocked-down by >85%. Gene expression was assessed by oligonucleotide
microarrays and compared to expression in nonsilenced controls. We
also investigated if genes were differentially expressed in 6 malignant
endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation
compared to 2 without MEN1 gene alterations.Results Using a cut-off
of >=2 times, 66 genes were found to be upregulated, and 22 were
downregulated in the MEN1-silenced clones. We corroborated the microarray
findings by performing quantitative-PCR on the RNA from the silencing
experiments for 7 of the 88 differentially regulated genes. Genes
involved in endocrine cell fate determination, as well as genes known
to be involved in NFkappaB, Notch, and Wnt signaling pathways, were
among genes verified as differentially regulated in vitro.Conclusions
The demonstration of pathways affected by silencing of MEN1 in vitro
provides novel insight into neoplastic processes of potential importance
in vivo, which warrants further study.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4M7V9XT-3/2/4e7e2c191f98a015d5d53c79c8827b3c}
}
@ARTICLE{Su2004,
author = {Su, Andrew I. and Wiltshire, Tim and Batalov, Serge and Lapp, Hilmar
and Ching, Keith A. and Block, David and Zhang, Jie and Soden, Richard
and Hayakawa, Mimi and Kreiman, Gabriel and Cooke, Michael P. and
Walker, John R. and Hogenesch, John B.},
title = {A gene atlas of the mouse and human protein-encoding transcriptomes},
journal = {PNAS},
year = {2004},
volume = {101},
pages = {6062--6067},
number = {16},
month = apr,
abstract = {The tissue-specific pattern of mRNA expression can indicate important
clues about gene function. High-density oligonucleotide arrays offer
the opportunity to examine patterns of gene expression on a genome
scale. Toward this end, we have designed custom arrays that interrogate
the expression of the vast majority of protein-encoding human and
mouse genes and have used them to profile a panel of 79 human and
61 mouse tissues. The resulting data set provides the expression
patterns for thousands of predicted genes, as well as known and poorly
characterized genes, from mice and humans. We have explored this
data set for global trends in gene expression, evaluated commonly
used lines of evidence in gene prediction methodologies, and investigated
patterns indicative of chromosomal organization of transcription.
We describe hundreds of regions of correlated transcription and show
that some are subject to both tissue and parental allele-specific
expression, suggesting a link between spatial expression and imprinting.},
url = {http://www.pnas.org/cgi/content/abstract/101/16/6062}
}
@ARTICLE{Su2010,
author = {Su, Chin-Fen and Wang, Yi-Chieh and Hsieh, Tsai-Hung and Lu, Chung-An
and Tseng, Tung-Hai and Yu, Su-May},
title = {A Novel MYBS3-Dependent Pathway Confers Cold Tolerance in Rice},
journal = {Plant Physiology},
year = {2010},
volume = {153},
pages = {145--158},
number = {1},
month = may,
abstract = {Rice (Oryza sativa) seedlings are particularly sensitive to chilling
in early spring in temperate and subtropical zones and in high-elevation
areas. Improvement of chilling tolerance in rice may significantly
increase rice production. MYBS3 is a single DNA-binding repeat MYB
transcription factor previously shown to mediate sugar signaling
in rice. In this study, we observed that MYBS3 also plays a critical
role in cold adaptation in rice. Gain- and loss-of-function analyses
indicated that MYBS3 was sufficient and necessary for enhancing cold
tolerance in rice. Transgenic rice constitutively overexpressing
MYBS3 tolerated 4{degrees}C for at least 1 week and exhibited no
yield penalty in normal field conditions. Transcription profiling
of transgenic rice overexpressing or underexpressing MYBS3 led to
the identification of many genes in the MYBS3-mediated cold signaling
pathway. Several genes activated by MYBS3 as well as inducible by
cold have previously been implicated in various abiotic stress responses
and/or tolerance in rice and other plant species. Surprisingly, MYBS3
repressed the well-known DREB1/CBF-dependent cold signaling pathway
in rice, and the repression appears to act at the transcriptional
level. DREB1 responded quickly and transiently while MYBS3 responded
slowly to cold stress, which suggests that distinct pathways act
sequentially and complementarily for adapting short- and long-term
cold stress in rice. Our studies thus reveal a hitherto undiscovered
novel pathway that controls cold adaptation in rice.},
url = {http://www.plantphysiol.org/cgi/content/abstract/153/1/145}
}
@ARTICLE{Su2011a,
author = {Su, Chun-lin and Chao, Ya-Ting and Alex Chang, Yao-Chien and Chen,
Wan-Chieh and Chen, Chun-Yi and Lee, Ann-Ying and Hwa, Kee Tuan and
Shih, Ming-Che},
title = {De Novo Assembly of Expressed Transcripts and Global Analysis of
the Phalaenopsis aphrodite Transcriptome},
journal = {Plant Cell Physiol.},
year = {2011},
volume = {52},
pages = {1501-1514},
number = {9},
abstract = {Being one of the largest families in the angiosperms, Orchidaceae
display a great biodiversity resulting from adaptation to diverse
habitats. Genomic information on orchids is rather limited, despite
their unique and interesting biological features, thus impeding advanced
molecular research. Here we report a strategy to integrate sequence
outputs of the moth orchid, Phalaenopsis aphrodite, from two high-throughput
sequencing platform technologies, Roche 454 and Illumina/Solexa,
in order to maximize assembly efficiency. Tissues collected for cDNA
library preparation included a wide range of vegetative and reproductive
tissues. We also designed an effective workflow for annotation and
functional analysis. After assembly and trimming processes, 233,823
unique sequences were obtained. Among them, 42,590 contigs averaging
875 bp in length were annotated to protein-coding genes, of which
7,263 coding genes were found to be nearly full length. The sequence
accuracy of the assembled contigs was validated to be as high as
99.9%. Genes with tissue-specific expression were also categorized
by profiling analysis with RNA-Seq. Gene products targeted to specific
subcellular localizations were identified by their annotations. We
concluded that, with proper assembly to combine outputs of next-generation
sequencing platforms, transcriptome information can be enriched in
gene discovery, functional annotation and expression profiling of
a non-model organism.},
doi = {10.1093/pcp/pcr097},
eprint = {http://pcp.oxfordjournals.org/cgi/reprint/52/9/1501.pdf},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/52/9/1501}
}
@ARTICLE{Su2011,
author = {Su, Hua and Hu, Nan and Yang, Howard H. and Wang, Chaoyu and Takikita,
Mikiko and Wang, Quan-Hong and Giffen, Carol and Clifford, Robert
and Hewitt, Stephen M. and Shou, Jian-Zhong and Goldstein, Alisa
M. and Lee, Maxwell P. and Taylor, Philip R.},
title = {Global Gene Expression Profiling and Validation in Esophageal Squamous
Cell Carcinoma and Its Association with Clinical Phenotypes},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {2955--2966},
number = {9},
month = may,
abstract = {Purpose: Esophageal squamous cell carcinoma (ESCC) is an aggressive
tumor with poor prognosis. Understanding molecular changes in ESCC
will enable identification of molecular subtypes and provide potential
targets for early detection and therapy. Experimental Design: We
followed up a previous array study with additional discovery and
confirmatory studies in new ESCC cases by using alternative methods.
We profiled global gene expression for discovery and confirmation,
and validated selected dysregulated genes with additional RNA and
protein studies. Results: A total of 159 genes showed differences
with extreme statistical significance (P < E-15) and 2-fold differences
or more in magnitude (tumor/normal RNA expression ratio, N = 53 cases),
including 116 upregulated and 43 downregulated genes. Of 41 genes
dysregulated in our prior array study, all but one showed the same
fold change directional pattern in new array studies, including 29
with 2-fold changes or more. Alternative RNA expression methods validated
array results: more than two thirds of 51 new cases examined by real-time
PCR (RT-PCR) showed 2-fold differences or more for all seven genes
assessed. Immunohistochemical protein expression results in 275 cases
which were concordant with RNA for five of six genes. Conclusion:
We identified an expanded panel of genes dysregulated in ESCC and
confirmed previously identified differentially expressed genes. Microarray-based
gene expression results were confirmed by RT-PCR and protein expression
studies. These dysregulated genes will facilitate molecular categorization
of tumor subtypes and identification of their risk factors, and serve
as potential targets for early detection, outcome prediction, and
therapy. Clin Cancer Res; 17(9); 2955-66. (C)2011 AACR.},
comment = {10.1158/1078-0432.CCR-10-2724},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/9/2955}
}
@ARTICLE{Su2004a,
author = {Su, Jack Meng Fen and Perlaky, Laszlo and Li, Xiao-Nan and Leung,
Hon-Chiu Eastwood and Antalffy, Barbara and Armstrong, Dawna and
Lau, Ching C.},
title = {Comparison of Ethanol Versus Formalin Fixation on Preservation of
Histology and RNA in Laser Capture Microdissected Brain Tissues},
journal = {Brain Pathology},
year = {2004},
volume = {14},
pages = {175--182},
number = {2},
abstract = {Although RNA can be retrieved from formalin-fixed, paraffin-embedded
(FFPE) tissues, the yield is low, and the RNA is fragmented. Recent
advances in gene expression profiling underscore the importance of
identifying a fixative that preserves histology and mRNA. We demonstrated
that, for immersion fixation of brains, 70% ethanol is superior to
formalin for mRNA preservation. RNA yield from ethanol-fixed tissues
was 70% of the yield from fresh frozen specimens, but only a negligible
quantity was recovered from formalin-fixed tissues. RNA from ethanol-fixed
brains showed integrity comparable to RNA from fresh frozen tissues,
and RT-PCR using RNA from ethanol-fixed tissues was consistently
successful. RNA from FFPE tissues composed of low-molecular weight
fragments, and their use in RT-PCR failed repeatedly. The yield and
quality of RNA from ethanol-fixed brains were unaffected after immersion
at 4°C for 2 weeks. In a blinded comparison to FFPE tissues, ethanol-fixed
specimens were judged to show comparable histology and superior immunostaining.
After laser capture microdissection (LCM), we failed to recover mRNA
from FFPE tissues but retrieved mRNA from ethanol-fixed tissues for
RT-PCR and cDNA microarray analysis. We conclude that 70% ethanol
preserves RNA integrity and is suitable for expression profiling
of brain tissues by LCM and cDNA microarray.},
issn = {1750-3639},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2004.tb00050.x}
}
@ARTICLE{Su2011b,
author = {Su, Li-Hsin and Pan, Yu-Jiao and Huang, Yu-Chang and Cho, Chao-Cheng
and Chen, Chia-Wei and Huang, Shao-Wei and Chuang, Sheng-Fung and
Sun, Chin-Hung},
title = {A Novel E2F-like Protein Involved in Transcriptional Activation of
Cyst Wall Protein Genes in Giardia lamblia},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {34101-34120},
number = {39},
abstract = {Giardia lamblia differentiates into resistant walled cysts for survival
outside the host and transmission. During encystation, synthesis
of cyst wall proteins is coordinately induced. The E2F family of
transcription factors in higher eukaryotes is involved in cell cycle
progression and cell differentiation. We asked whether Giardia has
E2F-like genes and whether they influence gene expression during
Giardia encystation. Blast searches of the Giardia genome database
identified one gene (e2f1) encoding a putative E2F protein with two
putative DNA-binding domains. We found that the e2f1 gene expression
levels increased significantly during encystation. Epitope-tagged
E2F1 was found to localize to nuclei. Recombinant E2F1 specifically
bound to the thymidine kinase and cwp1-3 gene promoters. E2F1 contains
several key residues for DNA binding, and mutation analysis revealed
that its binding sequence is similar to those of the known E2F family
proteins. The E2F1-binding sequences were positive cis-acting elements
of the thymidine kinase and cwp1 promoters. We also found that E2F1
transactivated the thymidine kinase and cwp1 promoters through its
binding sequences in vivo. Interestingly, E2F1 overexpression resulted
in a significant increase of the levels of CWP1 protein, cwp1-3 gene
mRNA, and cyst formation. We also found E2F1 can interact with Myb2,
a transcription factor that coordinate up-regulates the cwp1-3 genes
during encystation. Our results suggest that E2F family has been
conserved during evolution and that E2F1 is an important transcription
factor in regulation of the Giardia cwp genes, which are key to Giardia
differentiation into cysts.},
doi = {10.1074/jbc.M111.280206},
eprint = {http://www.jbc.org/cgi/reprint/286/39/34101.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/39/34101}
}
@ARTICLE{Su2008,
author = {Su, Shih-Chi and Mendoza, E. Adriana and Kwak, Hyeong-il and Bayless,
Kayla J.},
title = {Molecular profile of endothelial invasion of three-dimensional collagen
matrices: insights into angiogenic sprout induction in wound healing},
journal = {Am J Physiol Cell Physiol},
year = {2008},
volume = {295},
pages = {C1215--1229},
number = {5},
month = nov,
abstract = {Sprouting angiogenesis is a multistep process consisting of basement
membrane degradation, endothelial cell (EC) activation, proliferation,
invasion, lumen formation, and sprout stabilization. Such complexity
is consistent with a requirement for orchestration of individual
gene expression alongside multiple signaling pathways. To better
understand the mechanisms that direct the transformation of adherent
ECs on the surface of collagen matrices to develop multicellular
invading sprouts, we analyzed differential gene expression with time
using a defined in vitro model of EC invasion driven by the combination
of sphingosine-1-phosphate, basic FGF, and VEGF. Gene expression
changes were confirmed by real-time PCR and Western blot analyses.
A cohort of cell adhesion molecule genes involved in adherens junction
and cell-extracellular matrix (ECM) interactions were upregulated,
whereas a set of genes associated with tight junctions were downregulated.
Numerous genes encoding ECM proteins and proteases were induced,
indicating that biosynthesis and remodeling of ECM is indispensable
for sprouting angiogenesis. Knockdown of a highly upregulated gene,
a disintegrin and metalloproteinase with thrombospondin-type repeats-1
(ADAMTS1), decreased invasion responses, confirming a role for ADAMTS1
in mediating EC invasion. Furthermore, differential expression of
multiple members of the Wnt and Notch pathways was observed. Functional
experiments indicated that inhibition and activation of the Notch
signaling pathway stimulated and inhibited EC invasion responses,
respectively. This study has enhanced the molecular road map of gene
expression changes that occur during endothelial invasion and highlighted
the utility of three-dimensional models to study EC morphogenesis.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/295/5/C1215}
}
@ARTICLE{Su2009,
author = {Su, Shan-Yu and Hsieh, Ching-Liang and Wu, Shih-Lu and Cheng, Wen-Yu
and Li, Chia-Cheng and Lo, Hsin-Yi and Ho, Tin-Yun and Hsiang, Chien-Yun},
title = {Transcriptomic analysis of EGb 761-regulated neuroactive receptor
pathway in vivo},
journal = {Journal of Ethnopharmacology},
year = {2009},
volume = {123},
pages = {68--73},
number = {1},
month = may,
abstract = {Ethnopharmacological relevance EGb 761, a well-defined extract from
Ginkgo biloba, has been widely used in patients with cerebral disorders.Aim
of the study Although EGb 761 exhibits neuroprotective effects and
exerts beneficial effects on many neurological disorders, its mechanism
on the neuronal functions is unclear so far.Materials and methods
In this study, we used oligonucleotide microarray technique to investigate
the effect of EGb 761 on the transcriptional profile of mouse genes.
RNA samples were obtained from frontal cortex, straitum, and kidneys
after the oral administration of EGb 761 for seven consecutive days.Results
Our data showed that EGb 761 significantly altered the neuroactive
ligand-receptor interaction pathway in frontal cortex but not in
straitum and kidney. Then we analyzed 26 receptor genes that were
significantly altered by EGb 761 in this pathway and found that EGb
761 treatment highly up-regulated the subgroup of dopamine receptors,
especially dopamine receptor 1a (Drd1a), in frontal cortex. Quantitative
real-time reverse transcription-polymerase chain reaction and immunohistochemical
staining confirmed the increased level of Drd1a expression after
EGb 761 treatment.Conclusions In summary, we investigated for the
first time the overall effects of EGb 761 on the gene expression
in brain using a powerful systemic biological technique. Our results
suggested that EGb 761 altered unique pathways and regulated the
expressions of some specific neuronal receptor genes exclusively
in frontal cortex.},
issn = {0378-8741},
keywords = {Ginkgo biloba, EGb 761, Microarray, Neuroactive ligand-receptor interaction,
Dopamine receptor 1a},
url = {http://www.sciencedirect.com/science/article/B6T8D-4VRX672-2/2/fecbdd071200152d766a7da244cf0ceb}
}
@ARTICLE{Su2007,
author = {Su, Ying and Eason, Renea R. and Geng, Yan and Till, SR and Badger,
Thomas M. and Simmen, Rosalia C.M.},
title = {In utero exposure to maternal diets containing soy protein isolate,
but not genistein alone, protects young adult rat offspring from
NMU-induced mammary tumorigenesis},
journal = {Carcinogenesis},
year = {2007},
volume = {28},
pages = {1046--1051},
number = {5},
month = may,
abstract = {The linkage of nutrition and cancer prevention is an intriguing concept
that is gaining widespread support. Here, we investigated the influence
of developmental context on dietary protection against tumorigenesis
initiated by the direct-acting carcinogen N-methyl-N-nitrosourea
(NMU), and examined potential mechanisms underlying these effects.
Rats were exposed only in utero or for lifetime to American Institute
of Nutrition-93G diets made with casein (CAS), soy protein isolate
(SPI) or CAS supplemented with genistein (GEN). Mammary glands of
post-natal day (PND) 50 rats prior to NMU administration were examined
for apoptotic status, pro-apoptotic gene expression and immunoreactive
phosphatase and tensin homolog deleted on chromosome ten (PTEN) and
epithelial cadherin (E-cadherin) levels, whereas mammary tumor parameters
were evaluated 99 days post-NMU. Animals exposed only in utero to
SPI had increased tumor latency, decreased tumor multiplicity and
lower higher grade tumors, than those fed CAS. In utero exposure
to GEN resulted in similar tumor parameters as the CAS group, whereas
lifetime SPI exposure decreased tumor incidence that was not mimicked
by in utero exposure alone. Mammary glands of PND50 rats fed lifetime
SPI had increased terminal end bud apoptotic status and PTEN expression,
than the other diet groups. Rats exposed only in utero to SPI or
GEN had higher membrane E-cadherin in mammary structures than those
lifetime-fed CAS or SPI. Thus, limited exposure during gestation
to SPI can positively influence resistance to chemically induced
mammary tumorigenesis later in life. Preventative strategies against
mammary and other types of cancer might be uncovered by refinement
of the developmental window for dietary factor exposure.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/28/5/1046}
}
@ARTICLE{Su2009a,
author = {Su, Ying and Shankar, Kartik and Simmen, Rosalia C. M.},
title = {Early Soy Exposure via Maternal Diet Regulates Rat Mammary Epithelial
Differentiation by Paracrine Signaling from Stromal Adipocytes},
journal = {J. Nutr.},
year = {2009},
volume = {139},
pages = {945--951},
number = {5},
month = may,
abstract = {Diet-mediated changes in transcriptional programs that promote the
early differentiation of the mammary gland may lead to reduced breast
cancer risk. The disparity in adult breast cancer incidence between
Asian women and Western counterparts is attributed partly to high
soy food intake. Here, we conducted genome-wide profiling of mammary
tissues of weanling rats exposed to soy protein isolate (SPI) or
control casein (CAS) via maternal diet to evaluate the contribution
of early exposure on mammary gene expression. Of the identified 18
up- and 39 downregulated genes with SPI relative to CAS, a subset
was associated with lipid metabolic pathways, consistent with reduced
mammary adipocyte size and suggesting stromal adipocyte-specific
genomic changes. Female offspring of rats fed SPI tended to have
fewer terminal end buds (P = 0.06) and had significantly lower body
weight and abdominal fat mass. To demonstrate the functional consequence
of SPI-mediated adipocyte metabolic changes on neighboring mammary
epithelium, the expression of in vivo regulated genes in 3T3-L1 adipocytes
treated with soy isoflavone genistein and effects of the resultant
conditioned medium (CM) on the differentiation of HC11 mammary epithelial
cells were evaluated by quantitative RT-PCR and/or Western immunoblots.
In differentiated 3T3-L1, genistein decreased fatty acid synthase
and stearoyl-CoA desaturase and increased hydroxysteroid 11-{beta}
dehydrogenase 1 expression. CM from genistein-treated adipocytes
had higher adiponectin levels and augmented prolactin-induced, glucocorticoid-regulated
{beta}-casein levels. These findings suggest that soy-associated
components, by targeting mammary adipocytes, alter paracrine signaling
to enhance mammary epithelial differentiation, with important implications
for the prevention of breast cancer associated with obesity and obesity-related
diseases.},
url = {http://jn.nutrition.org/cgi/content/abstract/139/5/945}
}
@ARTICLE{Su2007a,
author = {Su, Ying and Simmen, Frank A. and Xiao, Rijin and Simmen, Rosalia
C. M.},
title = {Expression profiling of rat mammary epithelial cells reveals candidate
signaling pathways in dietary protection from mammary tumors},
journal = {Physiol Genomics},
year = {2007},
volume = {30},
pages = {8--16},
number = {1},
month = jun,
abstract = {The role of diet in the prevention of breast cancer is widely accepted,
yet little is known about how its biological effects mitigate susceptibility
to this disease. Soy consumption is associated with reduced breast
cancer risk in women, an effect largely attributed to the soy isoflavone
genistein (Gen). We previously showed reduced incidence of chemically
induced mammary tumors in young adult rats with lifetime dietary
intake of soy protein isolate (SPI) than in those fed the control
diet containing casein (Cas). To gain insight into signaling pathways
underlying dietary tumor protection, we performed genome-wide expression
profiling of mammary epithelial cells from young adult rats lifetime
fed Cas, SPI, or Cas supplemented with Gen. We identified mammary
epithelial genes regulated by SPI (79 total) and Gen (96 total) using
Affymetrix rat 230A GeneChip arrays and found minimal overlap in
gene expression patterns. We showed that the regulated transcripts
functionally clustered in biochemical pathways involving metabolism,
immune response, signal transduction, and ion transport. We confirmed
the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2,
Hes1) signaling components by SPI and/or Gen using quantitative real-time
PCR. Wnt pathway inhibition by Gen was supported by reduced cyclin
D1 immunoreactivity in mammary ductal epithelium of Gen relative
to Cas and SPI groups, despite comparable levels of membrane-localized
E-cadherin and {beta}-catenin. Identification of distinct Gen and
SPI responsive genes in mammary epithelial cells may define early
events contributing to tumor protection by diet relevant to the prevention
of breast and other types of cancer.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/30/1/8}
}
@ARTICLE{Su2009b,
author = {Su, Ying and Simmen, Rosalia C.M.},
title = {Soy isoflavone genistein upregulates epithelial adhesion molecule
E-cadherin expression and attenuates {beta}-catenin signaling in
mammary epithelial cells},
journal = {Carcinogenesis},
year = {2009},
volume = {30},
pages = {331--339},
number = {2},
month = feb,
abstract = {Breast cancer risk is highly modifiable by diet; however, mechanisms
underlying dietary protection against mammary tumorigenesis remain
poorly understood. A proportion of breast carcinomas is associated
with deregulation of {beta}-catenin stability and amplification of
c-Myc expression. We recently showed that dietary exposure to the
soy isoflavone genistein (Gen) inhibited Wnt transduction in rat
mammary epithelial cells in vivo. Here, we explored the role of Gen
on cell adhesion protein, E-cadherin, expression to downregulate
{beta}-catenin proto-oncogene function. In mammary glands of female
rats exposed to dietary Gen, E-cadherin and {beta}-catenin protein
levels were increased, concurrent with higher {beta}-casein gene
expression. In HC11 mouse mammary epithelial cells, Gen diminished
basal and Wnt-1-induced cell proliferation and attenuated Wnt-1 targets
c-Myc and Cyclin D1 expression. Whereas, Gen had no effect on E-cadherin
transcript levels, the abundance of membrane E-cadherin protein and
of E-cadherin-{beta}-catenin adhesion complex was increased by Gen,
attendant with downregulation of Wnt-1-induced free {beta}-catenin
accumulation in cytosol. Gen inhibition of Wnt-induced c-Myc expression
was mimicked by an estrogen receptor (ER)-{beta}-specific but not
ER-{alpha}-specific agonist and was attenuated with loss of ER-{beta}
expression, concordant with decreased E-cadherin expression. E-cadherin
small-interfering RNA targeting eliminated Gen inhibition of Wnt-stimulated
c-Myc expression and promoted Gen induction of basal c-Myc transcript
levels and subsequent proliferation. Our studies identify E-cadherin
as a Gen cellular target and demonstrate that the dichotomy in mammary
epithelial response to Gen may be a function of cellular E-cadherin
expression.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/30/2/331}
}
@ARTICLE{Su2005,
author = {Su, Yan Ru and Dove, Dwayne E. and Major, Amy S. and Hasty, Alyssa
H. and Boone, Branden and Linton, MacRae F. and Fazio, Sergio},
title = {Reduced ABCA1-Mediated Cholesterol Efflux and Accelerated Atherosclerosis
in Apolipoprotein E-Deficient Mice Lacking Macrophage-Derived ACAT1},
journal = {Circulation},
year = {2005},
volume = {111},
pages = {2373--2381},
number = {18},
month = may,
abstract = {Background-- Macrophage acyl-coenzyme A:cholesterol acyltransferase
1 (ACAT1) and apolipoprotein E (apoE) have been implicated in regulating
cellular cholesterol homeostasis and therefore play critical roles
in foam cell formation. Deletion of either ACAT1 or apoE results
in increased atherosclerosis in hyperlipidemic mice, possibly as
a consequence of altered cholesterol processing. We have studied
the effect of macrophage ACAT1 deletion on atherogenesis in apoE-deficient
(apoE-/-) mice with or without the restoration of macrophage apoE.
Methods and Results-- We used bone marrow transplantation to generate
apoE-/- mice with macrophages of 4 genotypes: apoE+/+/ACAT1+/+ (wild
type), apoE+/+/ACAT1-/- (ACAT-/-), apoE-/-/ACAT1+/+ (apoE-/-), and
apoE-/-/ACAT1-/- (2KO). When macrophage apoE was present, plasma
cholesterol levels normalized, and ACAT1 deficiency did not have
significant effects on atherogenesis. However, when macrophage apoE
was absent, ACAT1 deficiency increased atherosclerosis and apoptosis
in the proximal aorta. Cholesterol efflux to apoA-I was significantly
reduced (30% to 40%; P<0.001) in ACAT1-/- peritoneal macrophages
compared with ACAT1+/+ controls regardless of apoE expression. 2KO
macrophages had a 3- to 4-fold increase in ABCA1 message levels but
decreased ABCA1 protein levels relative to ACAT1+/+ macrophages.
Microarray analyses of ACAT1-/- macrophages showed increases in proinflammatory
and procollagen genes and decreases in genes regulating membrane
integrity, protein biosynthesis, and apoptosis. Conclusions-- Deficiency
of macrophage ACAT1 accelerates atherosclerosis in hypercholesterolemic
apoE-/- mice but has no effect when the hypercholesterolemia is corrected
by macrophage apoE expression. However, ACAT1 deletion impairs ABCA1-mediated
cholesterol efflux in macrophages regardless of apoE expression.
Changes in membrane stability, susceptibility to apoptosis, and inflammatory
response may also be important in this process.},
url = {http://circ.ahajournals.org/cgi/content/abstract/111/18/2373}
}
@ARTICLE{Su2008a,
author = {Su, You-Qiang and Sugiura, Koji and Wigglesworth, Karen and O'Brien,
Marilyn J. and Affourtit, Jason P. and Pangas, Stephanie A. and Matzuk,
Martin M. and Eppig, John J.},
title = {Oocyte regulation of metabolic cooperativity between mouse cumulus
cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis
in cumulus cells},
journal = {Development},
year = {2008},
volume = {135},
pages = {111--121},
number = {1},
month = jan,
abstract = {Oocyte-derived bone morphogenetic protein 15 (BMP15) and growth differentiation
factor 9 (GDF9) are key regulators of follicular development. Here
we show that these factors control cumulus cell metabolism, particularly
glycolysis and cholesterol biosynthesis before the preovulatory surge
of luteinizing hormone. Transcripts encoding enzymes for cholesterol
biosynthesis were downregulated in both Bmp15-/- and Bmp15-/- Gdf9+/-
double mutant cumulus cells, and in wild-type cumulus cells after
removal of oocytes from cumulus-cell-oocyte complexes. Similarly,
cholesterol synthesized de novo was reduced in these cumulus cells.
This indicates that oocytes regulate cumulus cell cholesterol biosynthesis
by promoting the expression of relevant transcripts. Furthermore,
in wild-type mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol and Ebp,
which encode enzymes required for cholesterol synthesis, were highly
expressed in cumulus cells compared with oocytes; and oocytes, in
the absence of the surrounding cumulus cells, synthesized barely
detectable levels of cholesterol. Furthermore, coincident with reduced
cholesterol synthesis in double mutant cumulus cells, lower levels
were also detected in cumulus-cell-enclosed double mutant oocytes
compared with wild-type oocytes. Levels of cholesterol synthesis
in double mutant cumulus cells and oocytes were partially restored
by co-culturing with wild-type oocytes. Together, these results indicate
that mouse oocytes are deficient in synthesizing cholesterol and
require cumulus cells to provide products of the cholesterol biosynthetic
pathway. Therefore, oocyte-derived paracrine factors, particularly,
BMP15 and GDF9, promote cholesterol biosynthesis in cumulus cells,
probably as compensation for oocyte deficiencies in cholesterol production.},
url = {http://dev.biologists.org/cgi/content/abstract/135/1/111}
}
@ARTICLE{Su2007b,
author = {Su, You-Qiang and Sugiura, Koji and Woo, Yong and Wigglesworth, Karen
and Kamdar, Sonya and Affourtit, Jason and Eppig, John J.},
title = {Selective degradation of transcripts during meiotic maturation of
mouse oocytes},
journal = {Developmental Biology},
year = {2007},
volume = {302},
pages = {104--117},
number = {1},
month = feb,
abstract = {There is massive destruction of transcripts during the maturation
of mouse oocytes. The objective of this project was to identify and
characterize the transcripts that are degraded versus those that
are stable during the transcriptionally silent germinal vesicle (GV)-stage
to metaphase II (MII)-stage transition using a microarray approach.
A system for oocyte transcript amplification using both internal
and 3'-poly(A) priming was utilized to minimize the impact of complex
variations in transcript polyadenylation prevalent during this transition.
Transcripts were identified and quantified using the Affymetrix Mouse
Genome 430 v2.0 GeneChip. The significantly changed and stable transcripts
were analyzed using Ingenuity Pathways Analysis and GenMAPP/MAPPFinder
to characterize the biological themes underlying global changes in
oocyte transcripts during maturation. It was concluded that the destruction
of transcripts during the GV to MII transition is a selective rather
than promiscuous process in mouse oocytes. In general, transcripts
involved in processes that are associated with meiotic arrest at
the GV-stage and the progression of oocyte maturation, such as oxidative
phosphorylation, energy production, and protein synthesis and metabolism,
were dramatically degraded. In contrast, transcripts encoding participants
in signaling pathways essential for maintaining the unique characteristics
of the MII-arrested oocyte, such as those involved in protein kinase
pathways, were the most prominent among the stable transcripts.},
issn = {0012-1606},
keywords = {Oocyte maturation, Metaphase II, Transcriptome, Polyadenylation, Mouse},
url = {http://www.sciencedirect.com/science/article/B6WDG-4KW5FH0-6/2/f1df0dfb23efcfa93919f428467b5c97}
}
@ARTICLE{Su2008b,
author = {Su, Zhiguang and Tsaih, Shirng-wern and Szatkiewicz, Jin and Shen,
Yuan and Paigen, Beverly},
title = {Candidate genes for plasma triglyceride, FFA, and glucose revealed
from an intercross between inbred mouse strains NZB/B1NJ and NZW/LacJ},
journal = {J. Lipid Res.},
year = {2008},
volume = {49},
pages = {1500--1510},
number = {7},
month = jul,
abstract = {To identify the genes controlling plasma concentrations of triglycerides
(TGs), FFAs, and glucose, we carried out a quantitative trait loci
(QTL) analysis of the closely related mouse strains New Zealand Black
(NZB/B1NJ) and New Zealand White (NZW/LacJ), which share 63% of their
genomes. The NZB x NZW F2 progeny were genotyped and phenotyped to
detect QTL, and then comparative genomics, bioinformatics, and sequencing
were used to narrow the QTL and reduce the number of candidate genes.
Triglyceride concentrations were linked to loci on chromosomes (Chr)
4, 7, 8, 10, and 18. FFA concentrations were affected by a significant
locus on Chr 4, a suggestive locus on Chr 16, and two interacting
loci on Chr 2 and 15. Plasma glucose concentrations were affected
by QTL on Chr 2, 4, 7, 8, 10, 15, 17, and 18. Comparative genomics
narrowed the QTL by 31% to 86%; haplotype analysis was usually able
to further narrow it by 80%. We suggest several candidate genes:
Gba2 on Chr 4, Irs2 on Chr 8, and Ppargc1b on Chr 18 for TG; A2bp1
on Chr 16 for FFA; and G6pc2 on Chr 2 and Timp3 on Chr 10 for glucose.},
url = {http://www.jlr.org/cgi/content/abstract/49/7/1500}
}
@ARTICLE{Suarez-Merino2005,
author = {Suarez-Merino, Blanca and Hubank, Mike and Revesz, Tamas and Harkness,
William and Hayward, Richard and Thompson, Dominic and Darling, John
L. and Thomas, David G.T. and Warr, Tracy J.},
title = {Microarray analysis of pediatric ependymoma identifies a cluster
of 112candidate genes including four transcripts at 22q12.1-q13.3},
journal = {Neuro Oncology},
year = {2005},
volume = {7},
pages = {20--31},
number = {1},
month = jan,
abstract = {Ependymomas are glial cell-derived tumors characterized by varying
degreesof chromosomal abnormalities and variability in clinical behavior.
Cytogeneticanaly-sis of pediatric ependymoma has failed to identify
consistent patternsof abnormalities, with the exception of monosomy
of 22 or structuralabnormalities of 22q. In this study, a total of
19 pediatric ependymomasamples were used in a series of expression
profiling, quantitative real-timePCR (Q-PCR), and loss of heterozygosity
experiments to identify candidategenes involved in the development
of this type of pediatric malignancy. Of the12,627 genes analyzed,
a subset of 112 genes emerged as being abnormallyexpressed when compared
to three normal brain controls. Genes with increasedexpression included
the oncogene WNT5A; the p53 homologuep63; and several cell cycle,
cell adhesion, and proliferation genes.Underexpressed genes comprised
the NF2 interact-ing geneSCHIP-1 and the adenomatous polyposis coli
(APC)-associatedgene EB1 among others. We validated the abnormal
expression of six ofthese genes by Q-PCR. The subset of differentially
expressed genes alsoincluded four underexpressed transcripts mapping
to 22q12.3-13.3. By Q-PCR weshow that one of these genes, CBX7 (22q13.1),
was deleted in 55% ofcases. Other genes mapping to cytogenetic hot
spots included two overexpressedand three underexpressed genes mapping
to 1q31-41 and 6q21-q24.3,respectively. These genes represent candidate
genes involved in ependymomatumorigenesis. To the authors' knowledge,
this is the first time microarrayanalysis and Q-PCR have been linked
to identify heterozygous/homozygousdeletions.},
url = {http://neuro-oncology.oxfordjournals.org/cgi/content/abstract/7/1/20}
}
@ARTICLE{Subbaiyan2012,
author = {Subbaiyan, Gopala K. and Waters, Daniel L. E. and Katiyar, Sanjay
K. and Sadananda, Ajanahalli R. and Vaddadi, Satyadev and Henry,
Robert J.},
title = {Genome-wide DNA polymorphisms in elite indica rice inbreds discovered
by whole-genome sequencing},
journal = {Plant Biotechnology Journal},
year = {2012},
pages = {no--no},
abstract = {Advances in next-generation sequencing technologies have aided discovery
of millions of genome-wide DNA polymorphisms, single nucleotide polymorphisms
(SNPs) and insertions–deletions (InDels), which are an invaluable
resource for marker-assisted breeding. Whole-genome resequencing
of six elite indica rice inbreds (three cytoplasmic male sterile
and three restorer lines) resulted in the generation of 338Â million
75-bp paired-end reads, which provided 85.4% coverage of the Nipponbare
genome. A total of 2Â 819Â 086 nonredundant DNA polymorphisms including
2Â 495Â 052 SNPs, 160Â 478 insertions and 163Â 556 deletions were
discovered between the inbreds and Nipponbare, providing an average
of 6.8 SNPs/kb across the genome. Distribution of SNPs and InDels
in the chromosome was nonrandom with SNP-rich and SNP-poor regions
being evident across the genome. A contiguous 4.3-Mb region on chromosome
5 with extremely low SNP density was identified. Overall, 83Â 262
nonsynonymous SNPs spanning 16Â 379 genes and 3620 nonsynonymous
InDels in 2625 genes have been discovered which provide valuable
insights into the basis underlying performance of the inbreds and
the hybrids between these inbred combinations. SNPs and InDels discovered
from this diverse set of indica rice inbreds not only enrich SNP
resources for molecular breeding but also enable the study of genome-wide
variations on hybrid performance.},
doi = {10.1111/j.1467-7652.2011.00676.x},
issn = {1467-7652},
keywords = {deletions, genome-wide variations, insertions, next-generation sequencing,
rice (Oryza sativa L.), single nucleotide polymorphism},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1467-7652.2011.00676.x}
}
@ARTICLE{Subramanian2009,
author = {Subramanian, Venkataramanan and Yadav, Jagjit S.},
title = {Role of P450 Monooxygenases in the Degradation of the Endocrine-Disrupting
Chemical Nonylphenol by the White Rot Fungus Phanerochaete chrysosporium},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {5570--5580},
number = {17},
month = sep,
abstract = {The white rot fungus Phanerochaete chrysosporium extensively degraded
the endocrine disruptor chemical nonylphenol (NP; 100% of 100 ppm)
in both nutrient-limited cultures and nutrient-sufficient cultures.
The P450 enzyme inhibitor piperonyl butoxide caused significant inhibition
([~]75%) of the degradation activity in nutrient-rich malt extract
(ME) cultures but no inhibition in defined low-nitrogen (LN) cultures,
indicating an essential role of P450 monooxygenase(s) in NP degradation
under nutrient-rich conditions. A genome-wide analysis using our
custom-designed P450 microarray revealed significant induction of
multiple P450 monooxygenase genes by NP: 18 genes were induced (2-
to 195-fold) under nutrient-rich conditions, 17 genes were induced
(2- to 6-fold) in LN cultures, and 3 were induced under both nutrient-rich
and LN conditions. The P450 genes Pff 311b (corresponding to protein
identification number [ID] 5852) and Pff 4a (protein ID 5001) showed
extraordinarily high levels of induction (195- and 167-fold, respectively)
in ME cultures. The P450 oxidoreductase (POR), glutathione S-transferase
(gst), and cellulose metabolism genes were also induced in ME cultures.
In contrast, certain metabolic genes, such as five of the peroxidase
genes, showed partial downregulation by NP. This study provides the
first evidence for the involvement of P450 enzymes in NP degradation
by a white rot fungus and the first genome-wide identification of
specific P450 genes responsive to an environmentally significant
toxicant.},
url = {http://aem.asm.org/cgi/content/abstract/75/17/5570}
}
@ARTICLE{Such2011,
author = {Such, Esperanza and Cervera, Jose and Valencia, Ana and Barragan,
Eva and Ibanez, Mariam and Luna, Irene and Fuster, Oscar and Perez-Sirvent,
Maria Luz and Senent, Leonor and Sempere, Amparo and Martinez, Jesus
and Martin-Aragones, Guillermo and Sanz, Miguel A.},
title = {A novel NUP98/RARG gene fusion in acute myeloid leukemia resembling
acute promyelocytic leukemia},
journal = {Blood},
year = {2011},
volume = {117},
pages = {242--245},
number = {1},
month = jan,
abstract = {Chromosomal translocations in hematological malignancies often result
in novel fusion chimeric genes. We report a case of acute myeloid
leukemia with a clonal translocation t(11;12)(p15;q13) displaying
morphologic and immunophenotypic features resembling the classical
hypergranular subtype of acute promyelocytic leukemia. The gene fused
to NUP98 (nucleoporin 98) was detected by comparative genomic hybridization
array as the retinoid acid receptor gamma gene (RARG). The involvement
of RARG in a chimeric fusion transcript has not been reported previously
in human leukemia.},
comment = {10.1182/blood-2010-06-291658},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/1/242}
}
@ARTICLE{Suchak2009,
author = {Suchak, Archna and Hunt, Nigel P. and Shah, Rishma and Sinanan, Andrea
C. M. and Lloyd, Tim and Lewis, Mark P.},
title = {Myosin proteins identified from masseter muscle using quantitative
reverse transcriptase-polymerase chain reaction--a pilot study of
the relevance to orthodontics},
journal = {Eur J Orthod},
year = {2009},
volume = {31},
pages = {196--201},
number = {2},
month = apr,
abstract = {There is a clearly established relationship between masticatory muscle
structure and facial form. Human studies in this area, however, have
been limited, especially in consideration of the myosin heavy chain
(MyHC) family of contractile proteins. The aim of this pilot study
was to assess if differences were detectable between genotype with
respect to MyHC isoforms and the vertical facial phenotype in a sample
of nine Caucasian female patients, age range 18-49 years, using a
novel rapid technique. Masseter muscle biopsies were taken from patients
with a range of vertical facial form. The levels of expression of
the MyHC isoform genes MYH 1, 2, 3, 6, 7, and 8 were compared with
the expression in a female calibrator patient aged 23 years with
normal vertical facial form, using quantitative reverse transcriptase-polymerase
chain reaction (RT-PCR) analysis. Statistical analysis was undertaken
using Pearson correlation coefficient. The results showed that there
were distinct differences in gene expression between patients with
a wide range of variation although changes in MYH1 were consistent
with one cephalometric variable, the maxillo-mandibular angle. The
full procedure, from start to finish, can be completed within half
a day. Rapid genotyping of patients in this way could reveal important
information of relevance to treatment. This technology has potential
as a diagnostic and prognostic aid when considering correction of
certain malocclusions.},
url = {http://ejo.oxfordjournals.org/cgi/content/abstract/31/2/196}
}
@ARTICLE{Sudre2005,
author = {Sudre, Karine and Cassar-Malek, Isabelle and Listrat, Anne and Ueda,
Yasuko and Leroux, Christine and Jurie, Catherine and Auffray, Charles
and Renand, Gilles and Martin, Patrice and Hocquette, Jean-François},
title = {Biochemical and transcriptomic analyses of two bovine skeletal muscles
in Charolais bulls divergently selected for muscle growth},
journal = {Meat Science},
year = {2005},
volume = {70},
pages = {267--277},
number = {2},
month = jun,
abstract = {This work aimed to investigate the consequences of muscle growth selection
on muscle characteristics. An oxidative muscle (Rectus abdominis,
RA) and a glycolytic one (Semitendinosus, ST) were studied in two
groups of six extreme young Charolais bulls of high or low muscle
growth. Mitochondrial activity was lower in muscles of bulls with
high muscle growth. Transcriptomic studies allowed the identification
of putatively differentially expressed genes. The differential expression
between genetic types of two genes in RA (a heat shock protein and
a thyroid receptor interacting protein) and of seven genes in ST
(including LEU5, tropomyosin 2, and sarcosin) was confirmed by different
statistical approaches or Northern blot analysis, as well as the
differential expression of five genes (including PSMD4 and DPM synthase)
between RA and ST. Both biochemical and transcriptomic results indicate
that selection on muscle growth potential is associated with reduced
slow-oxidative muscle characteristics. Further studies are required
to understand the physiological importance of genes whose expression
is changed by selection.},
issn = {0309-1740},
keywords = {Beef, Muscle growth, Transcriptomic analysis, Selection},
url = {http://www.sciencedirect.com/science/article/B6T9G-4FPX2W8-1/2/366223cad6b1b460c2ff7fea30277bcc}
}
@ARTICLE{Sudre2003,
author = {Sudre, Karine and Leroux, Christine and Pietu, Genevieve and Cassar-Malek,
Isabelle and Petit, Elisabeth and Listrat, Anne and Auffray, Charles
and Picard, Brigitte and Martin, Patrice and Hocquette, Jean-Francois},
title = {Transcriptome Analysis of Two Bovine Muscles during Ontogenesis},
journal = {J. Biochem.},
year = {2003},
volume = {133},
pages = {745--756},
number = {6},
month = jun,
abstract = {Macro-arrays, on which 1339 human skeletal muscle cDNA clone inserts
had been spotted as PCR products, were used to make large-scale measurement
of gene expression in bovine muscles during ontogenesis. Ten complex
cDNA targets derived from two mixed muscle samples, Rectus abdominis
(rather red oxidative muscle, RA) and Semitendinosus (rather white
glycolytic muscle, ST), were taken from foetuses at 4 different stages
(110, 180, 210, and 260 days post-conception) and from 15-month-old
young bulls to generate differential expression patterns. Each sample
analysed was prepared from a pool of RNA extracted from muscle tissues
sampled from at least 6 different animals. Approximately 200 expression
signals were validated and taken into account to provide a first
"bovine" muscle gene repertoire. Despite the relatively small number
of probes and the heterologous approach, this made it possible to
identify up to 7 genes differentially expressed between RA and ST,
depending on age. From 110 days post-conception to 15 months of age,
differences in the expression levels of 110 genes were detected in
the four comparisons between two consecutive ages. By comparing 260
days post-conception foetal muscles and adult muscles, up to 87 genes
were overexpressed, whereas only 7 genes were shown to be down-regulated.
Among these genes, 33% have unknown biological functions. Taken together,
the results reported here underline the importance of the last three
months of gestation in muscle myogenesis, and highlight new genes
involved in this process.},
url = {http://jb.oxfordjournals.org/cgi/content/abstract/133/6/745}
}
@ARTICLE{Suematsu2007,
author = {Suematsu, Nobuhiro and Ojaimi, Caroline and Kinugawa, Shintaro and
Wang, Zipping and Xu, Xiaobin and Koller MD, Akos and Recchia, Fabio
A. and Hintze, Thomas H.},
title = {Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing
Nitric Oxide Bioavailability Through Oxidative Stress},
journal = {Circulation},
year = {2007},
volume = {115},
pages = {255--262},
number = {2},
month = jan,
abstract = {Background-- Hyperhomocysteinemia (HHcy) has been considered a vascular
disease associated with increased levels of oxidative stress that
results in scavenging of NO. However, little is known of the impact
of HHcy on cardiac function and especially myocardial metabolism.
Methods and Results-- L-Homocysteine was intravenously infused into
conscious dogs, and the dogs were fed methionine to increase plasma
homocysteine to 10 {micro}mol/L for acute and 24 {micro}mol/L for
chronic HHcy. There was no significant change in hemodynamics with
HHcy. Veratrine-induced, NO-dependent, coronary vasodilation (Bezold-Jarisch
reflex) was reduced by 32% but was restored by simultaneous intravenous
infusion of ascorbic acid or apocynin. Acute and chronic HHcy significantly
increased uptake of glucose and lactate and decreased uptake of free
fatty acid by the heart. HHcy significantly decreased bradykinin-
or carbachol-induced reduction of myocardial oxygen consumption in
vitro, and this effect was completely restored by coincubation with
ascorbic acid, Tempol, or apocynin. Western blot analysis indicated
an increase in Nox2 (82%) and a reduction in endothelial nitric oxide
synthase (39%), phospho-endothelial nitric oxide synthase (39%),
and superoxide dismutase-1 (45%). Microarray analysis of gene expression
in heart tissue from chronic HHcy indicated a switch in cardiac phenotype
to enzymes that metabolize glucose. Conclusions-- HHcy directly modulates
substrate use by the heart independent of changes in hemodynamics
or ventricular function by reducing NO bioavailability through the
generation of superoxide. The progression of cardiac or coronary
heart disease associated with HHcy should be evaluated in light of
the impact of alterations in the regulation of cardiac metabolism
and substrate use.},
url = {http://circ.ahajournals.org/cgi/content/abstract/115/2/255}
}
@ARTICLE{Suenaga2005,
author = {Suenaga, Emi and Nakamura, Hiroshi},
title = {Evaluation of three methods for effective extraction of DNA from
human hair},
journal = {Journal of Chromatography B},
year = {2005},
volume = {820},
pages = {137--141},
number = {1},
month = jun,
abstract = {In this paper we evaluate three different methods for extracting DNA
from human hair i.e. the Chelex method, the QIAamp® DNA Mini Kit
method and the ISOHAIR® method. Analysis of DNA prepared from dyed
hairs with the ISOHAIR® method suggested that the DNA extracts contained
PCR inhibitors. On the other hand, few inhibition was observed when
DNA from dyed hairs were extracted using the Chelex method and the
QIAamp® DNA Mini Kit method. In conclusion, the Chelex method is
recommended for PCR experiments in view of its simplicity and cost-effectiveness.
To assess the reliability of the Chelex method for the extraction
of genomic DNA from both natural and dyed hair samples, minisatellite
variant repeat (MVR)-polymerase chain reaction (PCR) patterns of
Chelex-extracted DNA were compared using hairs (three natural black
hairs and three dyed hairs) with buccal swabs from six individuals.
Complete agreement was observed between hair and swab samples in
each individual, proving the utility of the Chelex method.},
issn = {1570-0232},
keywords = {DNA extraction, Hair analysis, Polymerase chain reaction inhibitor},
url = {http://www.sciencedirect.com/science/article/B6X0P-4FXHJBW-1/2/dd211c2fb751cc640953773e2198c166}
}
@ARTICLE{Suenaga2005a,
author = {Suenaga, Hikaru and Liu, Rui and Shiramasa, Yuko and Kanagawa, Takahiro},
title = {Novel Approach to Quantitative Detection of Specific rRNA in a Microbial
Community, Using Catalytic DNA},
journal = {Appl. Envir. Microbiol.},
year = {2005},
volume = {71},
pages = {4879--4884},
number = {8},
month = aug,
abstract = {We developed a novel method for the quantitative detection of the
16S rRNA of a specific bacterial species in the microbial community
by using deoxyribozyme (DNAzyme), which possesses the catalytic function
to cleave RNA in a sequence-specific manner. A mixture of heterogeneous
16S rRNA containing the target 16S rRNA was incubated with a species-specific
DNAzyme. The cleaved target 16S rRNA was separated from the intact
16S rRNA by electrophoresis, and then their amounts were compared
for the quantitative detection of target 16S rRNA. This method was
used to determine the abundance of the 16S rRNA of a filamentous
bacterium, Sphaerotilus natans, in activated sludge, which is a microbial
mixture used in wastewater treatment systems. The result indicated
that this DNAzyme-based approach would be applicable to actual microbial
communities.},
url = {http://aem.asm.org/cgi/content/abstract/71/8/4879}
}
@ARTICLE{Sueyoshi2010,
author = {Sueyoshi, Sumihisa and Mitsumata, Masako and Kusumi, Yoshiaki and
Niihashi, Mari and Esumi, Mariko and Yamada, Tsutomu and Sakurai,
Isamu},
title = {Increased expression of peroxisome proliferator-activated receptor
(PPAR)-[alpha] and PPAR-[gamma] in human atherosclerosis},
journal = {Pathology - Research and Practice},
year = {2010},
volume = {206},
pages = {429--438},
number = {7},
month = jul,
abstract = {To clarify the mechanism of atherosclerosis development in humans,
we studied the mRNA and protein expression of PPAR subtypes in various
types of atherosclerotic lesions and their correlation with cell
proliferation and macrophage invasion. Human aortas were obtained
from 35 autopsied cases, and each sample was divided into halves.
One half was used for the analysis of mRNA or protein expression
with RT-PCR or Western blotting, respectively. The other was microscopically
classified into atheromatous plaque (AP), fatty streak (FS), and
diffuse intimal thickening (DIT), and was analyzed immunohistochemically.
The mRNA levels of both PPARs increased significantly in atherosclerosis
and tended to increase in proportion to the severity of the lesion,
and the expression of PPAR-[alpha] correlated with that of PPAR-[gamma]
in FS and AP. The PPAR-[gamma] protein increased in AP. Monocytes/macrophages,
as well as endothelial and smooth muscle cells, expressed the PPAR-[gamma]
protein in plaques. This expression in the DIT was noted mainly in
macrophages but was not correlated with the density of macrophages,
suggesting that only certain macrophages express the PPARs in DIT.
Cell proliferation did not correlate with PPARs expression in any
lesion type. These findings suggest that PPARs may be associated
with atheromatous plaque formation, and that PPAR-[gamma] may be
involved in the early stages of human atherosclerosis.},
issn = {0344-0338},
keywords = {PPAR-[alpha] and PPAR-[gamma], Atherosclerosis, Human aorta, Macrophages,
Cell proliferation},
url = {http://www.sciencedirect.com/science/article/B7GW5-4YW37KJ-1/2/a7648e210dbb90c28edb8e556cb4f894}
}
@ARTICLE{Sugai2004,
author = {Sugai, Tetsuji And Kawamura, Meiko And Iritani, Shuji And Araki,
Kazuaki And Makifuchi, Takao And Imai, China And Nakamura, Ryosuke
And Kakita, Akiyoshi And Takahashi, Hitoshi And Nawa, Hiroyuki},
title = {Prefrontal Abnormality of Schizophrenia Revealed by DNA Microarray:
Impact on Glial and Neurotrophic Gene Expression},
journal = {Annals of the New York Academy of Sciences},
year = {2004},
volume = {1025},
pages = {84--91},
number = {1},
abstract = {Abstract: DNA microarrays with isotope labeling from gene-specific
primers enable sensitive detection of rare mRNAs, including neurotrophin
and cytokine mRNAs in the brain. Using high-quality RNA from postmortem
brains, gene-expression profiles covering 1373 genes were assessed
in the dorsoprefrontal cortex of schizophrenic patients and compared
with those of nonpsychiatric subjects. Statistical analysis of the
DNA microarray data confirmed the findings of a previous GeneChip
study by Hakak et al. (Proc. Natl. Acad. Sci. USA Vol. 98, pp. 4746-4751,
2001). The highest frequency of mRNA expression alterations occurred
in oligodendrocyte- and astrocyte-related genes in the prefrontal
cortex of schizophrenic patients, followed by the category for the
genes for growth factors/neurotrophic factors and their receptors.
Whether each mRNA signal represents the expression of the individual
genes or homologous genes in the category remains to be determined,
however. To control for potential medication effects on patients,
RNA from cynomolgus monkeys that were treated with haloperidol for
3 months was also subjected to DNA microarray analysis. A few genes
overlapped between the gene-expression profiles of the monkeys and
patients. The present profiling study suggests a potential biological
link between abnormal neurotrophic signals and impaired glial functions
in schizophrenic pathology.},
issn = {1749-6632},
keywords = {haloperidol, psychosis, oligodendrocyte, astrocyte, growth factor},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1196/annals.1316.011}
}
@ARTICLE{Sugarbaker2008,
author = {Sugarbaker, David J. and Richards, William G. and Gordon, Gavin J.
and Dong, Lingsheng and De Rienzo, Assunta and Maulik, Gautam and
Glickman, Jonathan N. and Chirieac, Lucian R. and Hartman, Mor-Li
and Taillon, Bruce E. and Du, Lei and Bouffard, Pascal and Kingsmore,
Stephen F. and Miller, Neil A. and Farmer, Andrew D. and Jensen,
Roderick V. and Gullans, Steven R. and Bueno, Raphael},
title = {Transcriptome sequencing of malignant pleural mesothelioma tumors},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {3521--3526},
number = {9},
month = mar,
abstract = {Cancers arise by the gradual accumulation of mutations in multiple
genes. We now use shotgun pyrosequencing to characterize RNA mutations
and expression levels unique to malignant pleural mesotheliomas (MPMs)
and not present in control tissues. On average, 266 Mb of cDNA were
sequenced from each of four MPMs, from a control pulmonary adenocarcinoma
(ADCA), and from normal lung tissue. Previously observed differences
in MPM RNA expression levels were confirmed. Point mutations were
identified by using criteria that require the presence of the mutation
in at least four reads and in both cDNA strands and the absence of
the mutation from sequence databases, normal adjacent tissues, and
other controls. In the four MPMs, 15 nonsynonymous mutations were
discovered: 7 were point mutations, 3 were deletions, 4 were exclusively
expressed as a consequence of imputed epigenetic silencing, and 1
was putatively expressed as a consequence of RNA editing. Notably,
each MPM had a different mutation profile, and no mutated gene was
previously implicated in MPM. Of the seven point mutations, three
were observed in at least one tumor from 49 other MPM patients. The
mutations were in genes that could be causally related to cancer
and included XRCC6, PDZK1IP1, ACTR1A, and AVEN.},
url = {http://www.pnas.org/cgi/content/abstract/105/9/3521}
}
@ARTICLE{Sugawara2010,
author = {Sugawara, Michiko and Okamoto, Kiyoshi and Kadowaki, Tadashi and
Kusano, Kazutomi and Fukamizu, Akiyoshi and Yoshimura, Tsutomu},
title = {Expressions of Cytochrome P450, UDP-Glucuronosyltranferase, and Transporter
Genes in Monolayer Carcinoma Cells Change in Subcutaneous Tumors
Grown As Xenografts in Immunodeficient Nude Mice},
journal = {Drug Metab. Dispos.},
year = {2010},
volume = {38},
pages = {526--533},
number = {3},
month = mar,
abstract = {Human tumors grown as xenografts in immunodeficient nude mice are
widely used to investigate the pharmacological activities of anticancer
drugs. Drug-metabolizing enzymes and transporters are expressed in
tumor cell lines and changes in drug metabolism and pharmacokinetics
(DMPK)-related gene expression after inoculation of the tumor cell
may affect the pharmacological activity of the drug under consideration.
The aims of the current study were to characterize DMPK-related gene
expression profiles and responses to typical cytochrome P450 inducers
in monolayer carcinoma cells grown in tissue culture versus those
inoculated into a xenograft model. We used the human hepatocellular
carcinoma cell line PLC/PRF/5 for this study and comprehensively
assessed changes in DMPK-related gene expression by reverse transcription-polymerase
chain reaction quantitation. CYP3A4 and UDP-glucuronosyltransferase
1A protein amounts were also analyzed by immunoprecipitation followed
by immunoblotting. We found that the expression of many DMPK-related
genes was elevated in the inoculated tumor compared with the monolayer
carcinoma cells, indicating changes in their gene regulation pathways,
presumably due to modulation of the nuclear receptor family of transcription
factors. In addition, monolayer carcinoma versus inoculated tumor
cells showed different responses to rifampicin, but similar responses
to dexamethasone or 3-methylcholanthrene. These results suggest that
inoculation of tumor cells results in the activation of drug metabolism
and transport function, leading to changes in the responses to pregnane
X receptor ligands and consequent discrepancies in the pharmacological
activities between in vitro monolayer carcinoma cells and in vivo
xenograft models.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/38/3/526}
}
@ARTICLE{Sugawara2009,
author = {Sugawara, Michiko and Okamoto, Kiyoshi and Kadowaki, Tadashi and
Kusano, Kazutomi and Fukamizu, Akiyoshi and Yoshimura, Tsutomu},
title = {Inoculation of Human Tumor Cells Alters the Basal Expression but
Not the Inducibility of Cytochrome P450 Enzymes in Tumor-Bearing
Mouse Liver},
journal = {Drug Metab. Dispos.},
year = {2009},
volume = {37},
pages = {2244--2254},
number = {11},
month = nov,
abstract = {The athymic nude mouse is often used to grow tumors for in vivo oncology
research, including the identification of anticancer drugs, whereas
wild-type mice are usually used to assess the pharmacokinetics (PK)
of new chemical entities. The relationship between PK and pharmacodynamics
(PD) provides useful mechanistic information and helps guide of the
clinical regimen. The aim of this study was to assess whether the
inoculation of human hepatocellular carcinoma cells (PLC/PRF/5) into
athymic nude mice alters the expression of genes encoding the drug-metabolizing
enzymes and transporters in host liver. The livers from nontumor-
and tumor-bearing mice were initially subjected to drug metabolism
gene microarray analysis. Microarray analysis indicated that tumor
inoculation had little effect on drug metabolism-related genes, including
several cytochrome P450s: Cyp1a, Cyp2b, and Cyp3a. This result was
further confirmed by reverse transcription-polymerase chain reaction
(RT-PCR). However, immunoreactive proteins of Cyp1a, Cyp2b, and Cyp3a
were suppressed by tumor inoculation. RT-PCR and Western immunoblotting
analysis showed that the inducibility of Cyp1a, Cyp2b, and Cyp3a
by 3-methylcholanthrene, phenobarbital, and dexamethasone, respectively,
was similar between nontumor- and tumor-bearing mice. These results
suggest that inoculation of human tumor cells into athymic nude mice
suppresses the expression of certain drug-metabolizing enzymes, which
may alter the PK and PD of antitumor drugs.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/37/11/2244}
}
@ARTICLE{Suggs2011,
author = {M. Jeanann L. Suggs and Vikas Majithia and Robert E. Lewis and Julius
M. Cruse},
title = {HLA DRB1*1503 allelic haplotype predominance and associated immunodysregulation
in systemic lupus erythematosus},
journal = {Experimental and Molecular Pathology},
year = {2011},
volume = {91},
pages = {548 - 562},
number = {2},
abstract = {Systemic lupus erythematosus (SLE) is a chronic, relapsing, and remitting
disease affecting primarily African American females of child bearing
age. Familial aggregation of this disease suggests that at least
part of the susceptibility for this disease is genetic, although
environmental and hormonal influences are also likely to play a role.
Early studies of genetic susceptibility to SLE revealed several of
the major histocompatibility complex molecules, namely HLA DR, to
be linked to SLE. Meta-analysis of genome scans has yielded loci
significant for lupus patients, one of which includes the MHC region.
Regulatory T cells are immunoregulatory cells that modulate activated
immune cells. These cells play a large role in homeostasis of the
immune responses and maintenance of immunologic tolerance, i.e.,
prevention of autoimmunity. Decreased numbers of regulatory T cells
have been described in many autoimmune diseases, including systemic
lupus erythematosus.
Autoantibody production in systemic lupus erythematosus and the resulting
immune complex formation and complex deposition into tissues are
arguably the central core of immune dysregulation leading to disease
manifestations and symptoms. Inability of the immune system to recognize
and inhibit autoreactive immune cells in this particular autoimmune
disease may be the result of inappropriate numbers and function of
regulatory T cells.
This study aims to characterize the immune cell population in patients
from our community suffering from systemic lupus erythematosus and
to prove that these patients exhibit a unique cellular profile compared
to healthy age, race and gender matched control subjects. Surprisingly,
our findings demonstrate that patients from the local Mississippi
area exhibit increased proportions of CD25+ FoxP3+ regulatory T cells
and CD25+ FoxP3− T cells (of CD45+ CD3+ CD4+ helper T cells) as
compared to healthy controls.
HLA tissue-typing of these lupus patients revealed a prominent subgroup
(~ 30%) of patients possessing the HLA DRB1*1503 allele. The
investigation of this subgroup demonstrated regulatory T cell composition
similar to that of the total lupus group and to that of the non-HLA
DRB1*1503 subgroup.
Genetic analysis for molecular gene expression levels of various lupus-associated
genes by real-time PCR demonstrated a unique profile as compared
to healthy controls. Increased gene expression of FoxP3 together
with decreased gene expression levels of GATA3, TNFAIP3, and TNFSF4
suggest that variations in gene products compared to healthy controls
may be playing a role in the immune cell dysregulation and disproportionate
CD25+ FoxP3+ regulatory T cells.},
doi = {10.1016/j.yexmp.2011.03.006},
issn = {0014-4800},
keywords = {Systemic lupus erythematosus},
url = {http://www.sciencedirect.com/science/article/pii/S0014480011000293}
}
@ARTICLE{Suggs2011a,
author = {Suggs, M. Jeanann L. and Majithia, Vikas and Lewis, Robert E. and
Cruse, Julius M.},
title = {HLA DRB*1503 allelic haplotype predominance and associated immunodysregulation
in systemic lupus erythematosus},
journal = {Experimental and Molecular Pathology},
year = {2011},
volume = {91, 2},
pages = {548–562},
abstract = {Systemic lupus erythematosus (SLE) is a chronic, relapsing, and remitting
disease affecting primarily African American females of child bearing
age. Familial aggregation of this disease suggests that at least
part of the susceptibility for this disease is genetic, although
environmental and hormonal influences are also likely to play a role.
Early studies of genetic susceptibility to SLE revealed several of
the major histocompatibility complex molecules, namely HLA DR, to
be linked to SLE. Meta-analysis of genome scans has yielded loci
significant for lupus patients, one of which includes the MHC region.
Regulatory T cells are immunoregulatory cells that modulate activated
immune cells. These cells play a large role in homeostasis of the
immune responses and maintenance of immunologic tolerance, i.e.,
prevention of autoimmunity. Decreased numbers of regulatory T cells
have been described in many autoimmune diseases, including systemic
lupus erythematosus. Autoantibody production in systemic lupus erythematosus
and the resulting immune complex formation and complex deposition
into tissues are arguably the central core of immune dysregulation
leading to disease manifestations and symptoms. Inability of the
immune system to recognize and inhibit autoreactive immune cells
in this particular autoimmune disease may be the result of inappropriate
numbers and function of regulatory T cells. This study aims to characterize
the immune cell population in patients from our community suffering
from systemic lupus erythematosus and to prove that these patients
exhibit a unique cellular profile compared to healthy age, race and
gender matched control subjects. Surprisingly, our findings demonstrate
that patients from the local Mississippi area exhibit increased proportions
of CD25+ FoxP3+ regulatory T cells and CD25+ FoxP3- T cells (of CD45+
CD3+ CD4+ helper T cells) as compared to healthy controls. HLA tissue-typing
of these lupus patients revealed a prominent subgroup (~ 30%) of
patients possessing the HLA DRB1*1503 allele. The investigation of
this subgroup demonstrated regulatory T cell composition similar
to that of the total lupus group and to that of the non-HLA DRB1*1503
subgroup. Genetic analysis for molecular gene expression levels of
various lupus-associated genes by real-time PCR demonstrated a unique
profile as compared to healthy controls. Increased gene expression
of FoxP3 together with decreased gene expression levels of GATA3,
TNFAIP3, and TNFSF4 suggest that variations in gene products compared
to healthy controls may be playing a role in the immune cell dysregulation
and disproportionate CD25+ FoxP3+ regulatory T cells.},
issn = {0014-4800},
keywords = {Systemic lupus erythematosus, Regulatory T cells, Tregs, HLA, Immune
dysregulation},
url = {http://www.sciencedirect.com/science/article/pii/S0014480011000293}
}
@ARTICLE{Sugimori2009,
author = {Sugimori, Daisuke},
title = {Purification, characterization, and gene cloning of sphingomyelinase
C from Streptomyces griseocarneus NBRC13471},
journal = {Journal of Bioscience and Bioengineering},
year = {2009},
volume = {108},
pages = {293--298},
number = {4},
month = oct,
abstract = {Sphingomyelinase C (SMC) was purified to homogeneity from the culture
supernatant of Streptomyces griseocarneus NBRC13471. The purified
enzyme appeared as a single band of 38 kDa by using an electropherogram
trace. The molecular mass of the enzyme as determined by MALDI-TOF
MS was 32,102 Da, indicating that SMC is monomeric in nature. Under
experimental conditions, the highest enzyme activity was found at
pH 9.0 and 50-55 °C, and the enzyme was stable from pH 5 to 10 and
up to 37 °C. The SMC activity requires Mg2+ or Mn2+ and the order
of potency to enhance the activity was Zn2+ >= Mn2+ > Cu2+ >= Fe2+.
Phenylmethylsulfonyl fluoride and EDTA inhibited the enzyme activity,
showing that SMC belongs to a group of metalloenzymes and a class
of serine hydrolases. The enzyme activity was inhibited by DTT, but
not by mercaptoethanol and iodoacetamide. SDS inhibited the enzyme
activity; by contrast, Triton X-100 stimulated the activity. The
N-terminal and internal amino-acid sequences were determined as H2N-APAAATPSLK,
AREIAAAGFFQGND, and NTVVQETSAP. The gene encoding SMC consisted of
1020 bp encoding a signal peptide of 42 amino acids and a mature
protein of 297 amino acids with a calculated molecular mass of 32,125 Da.
The conserved region of DNase I-like family enzymes and the amino
acid residues that are highly conserved in the active center of other
bacterial SMCs were also found in the deduced amino acid sequence
of S. griseocarneus SMC.},
issn = {1389-1723},
keywords = {Sphingomyelinase C, Streptomyces, Purification, Characterization,
Gene cloning},
url = {http://www.sciencedirect.com/science/article/B6VSD-4X372N3-5/2/8c6ec25adb78daeaa7dcf1f71875a594}
}
@ARTICLE{Sugimoto2010,
author = {Sugimoto, Kaoru and Jiao, Yuling and Meyerowitz, Elliot M.},
title = {Arabidopsis Regeneration from Multiple Tissues Occurs via a Root
Development Pathway},
journal = {Developmental Cell},
year = {2010},
volume = {18},
pages = {463--471},
number = {3},
month = mar,
abstract = {Summary Unlike most animal cells, plant cells can easily regenerate
new tissues from a wide variety of organs when properly cultured.
The common elements that provide varied plant cells with their remarkable
regeneration ability are still largely unknown. Here we describe
the initial process of Arabidopsis in vitro regeneration, where a
pluripotent cell mass termed callus is induced. We demonstrate that
callus resembles the tip of a root meristem, even if it is derived
from aerial organs such as petals, which clearly shows that callus
formation is not a simple reprogramming process backward to an undifferentiated
state as widely believed. Furthermore, callus formation in roots,
cotyledons, and petals is blocked in mutant plants incapable of lateral
root initiation. It thus appears that the ectopic activation of a
lateral root development program is a common mechanism in callus
formation from multiple organs.},
issn = {1534-5807},
keywords = {DEVBIO, SIGNALING, STEMCELL},
url = {http://www.sciencedirect.com/science/article/B6WW3-4YM3SYC-H/2/9616edc9d790321bccd5b448b5da4b65}
}
@ARTICLE{Sugimoto2009,
author = {Sugimoto, Takashi and Seki, Naohiko and Shimizu, Satoya and Kikkawa,
Naoko and Tsukada, Jun and Shimada, Hideaki and Sasaki, Keita and
Hanazawa, Toyoyuki and Okamoto, Yoshitaka and Hata, Akira},
title = {The galanin signaling cascade is a candidate pathway regulating oncogenesis
in human squamous cell carcinoma},
journal = {Genes Chromosom. Cancer},
year = {2009},
volume = {48},
pages = {132--142},
number = {2},
abstract = {Abstract 10.1002/gcc.20626.abs To identify putative biomarkers in
squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations
and gene expression studies in 10 SCC cell lines were performed using
array–comparative genomic hybridization (CGH) and oligo-microarray
techniques. The most frequent changes were gains of 11q13.1-13.3
and losses of 18q12.1-23 in SCC. Furthermore, the expression levels
of the sets of genes at both these loci in SCC were measured using
microarray analysis. By combining the array-CGH with the microarray
data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression
correlated with chromosomal alterations were identified. To verify
the expression levels of the identified genes, we used expression
analysis data derived from our earlier study of clinical specimens.
In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF3B2,
and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a
significant difference between normal and tumor samples. GAL, coding
for the neuropeptide galanin, and GALR1, a galanin receptor, were
identified as candidate genes of oncogenesis in SCC. The expression
levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time
PCR. The expression ratio between GAL and GALR1 showed a significant
negative correlation. GALR1 is a G-protein-coupled receptor that
activates GTP-binding proteins to trigger signaling cascades such
as the mitogen-activated protein kinase pathway, and is a well-established
mitogenic pathway. This further supports the hypothesis that the
genes involved in the GAL signaling cascade are candidates for regulation
of oncogenesis in SCC. © 2008 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20626}
}
@ARTICLE{Sugulle2009,
author = {Sugulle, Meryam and Dechend, Ralf and Herse, Florian and Weedon-Fekjaer,
M. Susanne and Johnsen, Guro M. and Brosnihan, K. Bridget and Anton,
Lauren and Luft, Friedrich C. and Wollert, Kai C. and Kempf, Tibor
and Staff, Anne Cathrine},
title = {Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia
and in Pregnancy Complicated by Diabetes Mellitus},
journal = {Hypertension},
year = {2009},
volume = {54},
pages = {106--112},
number = {1},
month = jul,
abstract = {Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming
growth factor-{beta}-related cytokine, is emerging as a new risk
marker in patients with cardiovascular disease. We explored GDF-15
in preeclampsia and in diabetic pregnancies, because these conditions
are associated with augmented risk for cardiovascular disease, both
in mother and in offspring. Plasma from pregnant women (n=267; controls:
n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed
preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and
amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental
GDF-15 mRNA and protein expression levels were analyzed by quantitative
real-time PCR and immunoblots in 78 and 18 pregnancies, respectively.
Conditioned media from preeclamptic (n=6) and control (n=6) villous
placenta explants were analyzed by immunoassay for GDF-15. Median
maternal GDF-15 concentration was elevated in those with diabetes
mellitus, as compared with controls (91 549 versus 79 875 ng/L; P=0.02).
Median GDF-15 concentration was higher in patients with preeclampsia
than in controls in term maternal blood samples (127 061 versus 80
319 ng/L; P<0.001). In the fetal circulation and amniotic fluid,
GDF-15 was elevated in preeclampsia and superimposed preeclampsia
in diabetes mellitus, as compared with controls. GDF-15 placental
mRNA expression was elevated in preeclampsia, as compared with controls
(P=0.002). Placenta immunoblots confirmed a single GDF-15 protein
band, and a time-dependent increase in GDF-15 protein was detected
in the conditioned media. Our study is the first to show that GDF-15
is dysregulated, both in preeclampsia and in diabetic pregnancies.
The mechanisms and diagnostic implications of these findings remain
to be explored.},
url = {http://hyper.ahajournals.org/cgi/content/abstract/54/1/106}
}
@ARTICLE{Suleman2012,
author = {Suleman, Farhana and Gualeni, Benedetta and Gregson, Hannah J. and
Leighton, Matthew P. and Piróg, Katarzyna A. and Edwards, Sarah
and Holden, Paul and Boot-Handford, Raymond P. and Briggs, Michael
D.},
title = {A novel form of chondrocyte stress is triggered by a COMP mutation
causing pseudoachondroplasia},
journal = {Human Mutation},
year = {2012},
volume = {33},
pages = {218--231},
number = {1},
abstract = {Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric
matrix protein (COMP) and the p.D469del mutation within the type
III repeats of COMP accounts for approximately 30% of PSACH. To determine
disease mechanisms of PSACH in vivo, we introduced the Comp D469del
mutation into the mouse genome. Mutant animals were normal at birth
but grew slower than their wild-type littermates and developed short-limb
dwarfism. In the growth plates of mutant mice chondrocyte columns
were reduced in number and poorly organized, while mutant COMP was
retained within the endoplasmic reticulum (ER) of cells. Chondrocyte
proliferation was reduced and apoptosis was both increased and spatially
dysregulated. Previous studies on COMP mutations have shown mutant
COMP is co-localized with chaperone proteins, and we have reported
an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple
epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3,
Comp etc (V194D). However, we found no evidence of UPR in this mouse
model of PSACH. In contrast, microarray analysis identified expression
changes in groups of genes implicated in oxidative stress, cell cycle
regulation, and apoptosis, which is consistent with the chondrocyte
pathology. Overall, these data suggest that a novel form of chondrocyte
stress triggered by the expression of mutant COMP is central to the
pathogenesis of PSACH. Hum Mutat 33:218–231, 2012. © 2011 Wiley
Periodicals, Inc.},
doi = {10.1002/humu.21631},
issn = {1098-1004},
keywords = {pseudoachondroplasia, cartilage oligomeric matrix protein, chondrocyte
stress},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.21631}
}
@ARTICLE{Sullivan2007,
author = {Sullivan, B. D. and Richards, S. M. and Talbot, D. and Schmidt, T.
A. and Sullivan, D. A.},
title = {Proteoglycan 4 mRNA Expression in Human Corneal and Conjunctival
Epithelial Cells},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {795--},
number = {5},
month = may,
abstract = {PurposeProteoglycan 4 (PRG4) may play a critical role as a boundary
lubricant in articulating joints. This secreted glycoprotein, which
is also called lubricin and superficial zone protein, protects cartilaginous
surfaces against frictional forces, cell adhesion and protein deposition.
We hypothesize that PRG4 may serve an analogous role on the ocular
surface and protect the cornea and conjunctiva against significant
shear forces generated during an eyelid blink. We also hypothesize
that PRG4 is synthesized by corneal and conjunctival epithelial cells
and secreted onto the ocular surface. The purpose of this study was
to determine whether ocular surface cells express the gene for PRG4.
MethodsHuman corneal epithelial cells were isolated from the corneoscleral
rims of male and female donors. Cells were processed either directly
(n = 8), or first cultured (n = 2). We also obtained bulbar conjunctivae
during surgical procedures (n = 2), conjunctival impression cytology
samples (n = 9), and immortalized human conjunctival epithelial cells
after culture (n = 1). Samples were processed for the analysis of
PRG4 mRNA by using primarily RT-PCR (n = 18), but also Affymetrix
gene chips (n = 4). The PRG4 primers for PCR spanned over 1 kbp of
intron sequences, in order to suppress amplification of contaminating
chromosomal DNA. Amplified samples were screened for the presence
of PRG4 products by using agarose gel electrophoresis and an Agilent
2100 Bioanalyzer. To confirm the identity of amplicons, PCR products
from cornea samples (n = 2) and conjunctival epithelial cells (n
= 1) were sequenced with a 3100 Genetic Analyzer and resulting data
were analyzed with BLASTn searches. ResultsOur findings demonstrate
that PRG4 mRNA is present in all human corneal and conjunctival epithelial
cell and impression cytology samples. The identity of PRG4 PCR products
was confirmed by DNA sequence analysis. ConclusionsOur results show
that PRG4 is transcribed in human corneal and conjunctival epithelial
cells. (The authors thank Sandra Michaud and Pablo Argueso for their
assistance.)},
url = {http://abstracts.iovs.org/cgi/content/abstract/48/5/795}
}
@ARTICLE{Sullivan2005,
author = {Sullivan, Chris J. and Teal, Thomas H. and Luttrell, Ian P. and Tran,
Khoa B. and Peters, Mette A. and Wessells, Hunter},
title = {Microarray analysis reveals novel gene expression changes associated
with erectile dysfunction in diabetic rats},
journal = {Physiol Genomics},
year = {2005},
volume = {23},
pages = {192--205},
number = {2},
month = oct,
abstract = {To investigate the full range of molecular changes associated with
erectile dysfunction (ED) in Type 1 diabetes, we examined alterations
in penile gene expression in streptozotocin-induced diabetic rats
and littermate controls. With the use of Affymetrix GeneChip arrays
and statistical filtering, 529 genes/transcripts were considered
to be differentially expressed in the diabetic rat cavernosum compared
with control. Gene Ontology (GO) classification indicated that there
was a decrease in numerous extracellular matrix genes (e.g., collagen
and elastin related) and an increase in oxidative stress-associated
genes in the diabetic rat cavernosum. In addition, PubMatrix literature
mining identified differentially expressed genes previously shown
to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein
lipase, and Cd36] as well as genes involved in the modulation of
the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine
C-X3-C motif ligand 1). Real-time PCR was used to confirm changes
in expression for 23 relevant genes. Further validation of Cp expression
in the diabetic rat cavernosum demonstrated increased mRNA levels
of the secreted and anchored splice variants of Cp. CP protein levels
showed a 1.9-fold increase in tissues from diabetic rats versus controls.
Immunohistochemistry demonstrated localization of CP protein in cavernosal
sinusoids of control and diabetic animals, including endothelial
and smooth muscle layers. Overall, this study broadens the scope
of candidate genes and pathways that may be relevant to the pathophysiology
of diabetes-induced ED as well as highlights the potential complexity
of this disorder.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/23/2/192}
}
@ARTICLE{Sullivan2010,
author = {Sullivan, Matthew B. and Huang, Katherine H. and Ignacio-Espinoza,
Julio C. and Berlin, Aaron M. and Kelly, Libusha and Weigele, Peter
R. and DeFrancesco, Alicia S. and Kern, Suzanne E. and Thompson,
Luke R. and Young, Sarah and Yandava, Chandri and Fu, Ross and Krastins,
Bryan and Chase, Michael and Sarracino, David and Osburne, Marcia
S. and Henn, Matthew R. and Chisholm, Sallie W.},
title = {Genomic analysis of oceanic cyanobacterial myoviruses compared with
T4-like myoviruses from diverse hosts and environments},
journal = {Environmental Microbiology},
year = {2010},
volume = {12},
pages = {3035--3056},
number = {11},
abstract = {Summary T4-like myoviruses are ubiquitous, and their genes are among
the most abundant documented in ocean systems. Here we compare 26
T4-like genomes, including 10 from non-cyanobacterial myoviruses,
and 16 from marine cyanobacterial myoviruses (cyanophages) isolated
on diverse Prochlorococcus or Synechococcus hosts. A core genome
of 38 virion construction and DNA replication genes was observed
in all 26 genomes, with 32 and 25 additional genes shared among the
non-cyanophage and cyanophage subsets, respectively. These hierarchical
cores are highly syntenic across the genomes, and sampled to saturation.
The 25 cyanophage core genes include six previously described genes
with putative functions (psbA, mazG, phoH, hsp20, hli03, cobS), a
hypothetical protein with a potential phytanoyl-CoA dioxygenase domain,
two virion structural genes, and 16 hypothetical genes. Beyond previously
described cyanophage-encoded photosynthesis and phosphate stress
genes, we observed core genes that may play a role in nitrogen metabolism
during infection through modulation of 2-oxoglutarate. Patterns among
non-core genes that may drive niche diversification revealed that
phosphorus-related gene content reflects source waters rather than
host strain used for isolation, and that carbon metabolism genes
appear associated with putative mobile elements. As well, phages
isolated on Synechococcus had higher genome-wide %G+C and often contained
different gene subsets (e.g. petE, zwf, gnd, prnA, cpeT) than those
isolated on Prochlorococcus. However, no clear diagnostic genes emerged
to distinguish these phage groups, suggesting blurred boundaries
possibly due to cross-infection. Finally, genome-wide comparisons
of both diverse and closely related, co-isolated genomes provide
a locus-to-locus variability metric that will prove valuable for
interpreting metagenomic data sets.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2010.02280.x}
}
@ARTICLE{Sulonen2011,
author = {Sulonen, Anna-Maija and Ellonen, Pekka and Almusa, Henrikki and Lepisto,
Maija and Eldfors, Samuli and Hannula, Sari and Miettinen, Timo and
Tyynismaa, Henna and Salo, Perttu and Heckman, Caroline and Joensuu,
Heikki and Raivio, Taneli and Suomalainen, Anu and Saarela, Janna},
title = {Comparison of solution-based exome capture methods for next generation
sequencing},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R94},
number = {9},
abstract = {BACKGROUND:Techniques enabling targeted re-sequencing of the protein
coding sequences of the human genome on next generation sequencing
instruments are of great interest. We conducted a systematic comparison
of the solution-based exome capture kits provided by Agilent and
Roche NimbleGen. A control DNA sample was captured with all four
capture methods and prepared for Illumina GAII sequencing. Sequence
data from additional samples prepared with the same protocols were
also used in the comparison.RESULTS:We developed a bioinformatics
pipeline for quality control, short read alignment, variant identification
and annotation of the sequence data. In our analysis, a larger percentage
of the high quality reads from the NimbleGen captures than from the
Agilent captures aligned to the capture target regions. High GC content
of the target sequence was associated with poor capture success in
all exome enrichment methods. Comparison of mean allele balances
for heterozygous variants indicated a tendency to have more reference
bases than variant bases in the heterozygous variant positions within
the target regions in all methods. There was virtually no difference
in the genotype concordance compared to genotypes derived from SNP
arrays. A minimum of 11x coverage was required to make a heterozygote
genotype call with 99% accuracy when compared to common SNPs on genome-wide
association arrays.CONCLUSIONS:Libraries captured with NimbleGen
kits aligned more accurately to the target regions. The updated NimbleGen
kit most efficiently covered the exome with a minimum coverage of
20x, yet none of the kits captured all the Consensus Coding Sequence
annotated exons.},
doi = {10.1186/gb-2011-12-9-r94},
issn = {1465-6906},
pubmedid = {21955854},
url = {http://genomebiology.com/2011/12/9/R94}
}
@ARTICLE{Sultmann2005,
author = {Sultmann, Holger and Heydebreck, Anja von and Huber, Wolfgang and
Kuner, Ruprecht and Buness, Andreas and Vogt, Markus and Gunawan,
Bastian and Vingron, Martin and Fuzesi, Laszlo and Poustka, Annemarie},
title = {Gene Expression in Kidney Cancer Is Associated with Cytogenetic Abnormalities,
Metastasis Formation, and Patient Survival},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {646--655},
number = {2},
month = jan,
abstract = {Current diagnosis of renal cancer consists of histopathologic examination
of tissue sections and classification into tumor stages and grades
of malignancy. Until recently, molecular differences between tumor
types were largely unknown. To examine such differences, we did gene
expression measurements of 112 renal cell carcinoma and normal kidney
samples on renal cell carcinoma-specific cDNA microarrays containing
4,207 genes and expressed sequence tags. The gene expression patterns
showed deregulation of complete biological pathways in the tumors.
Many of the molecular changes corresponded well to the histopathologic
tumor types, and a set of 80 genes was sufficient to classify tumors
with a very low error rate. Distinct gene expression signatures were
associated with chromosomal abnormalities of tumor cells, metastasis
formation, and patient survival. The data highlight the benefit of
microarrays to detect novel tumor classes and to identify genes that
are associated with patient variables and tumor properties.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/2/646}
}
@ARTICLE{Sumegi2011,
author = {Sumegi, Janos and Barnes, Michael G. and Nestheide, Shawnagay V.
and Molleran-Lee, Susan and Villanueva, Joyce and Zhang, Kejian and
Risma, Kimberly A. and Grom, Alexei A. and Filipovich, Alexandra
H.},
title = {Gene expression profiling of peripheral blood mononuclear cells from
children with active hemophagocytic lymphohistiocytosis},
journal = {Blood},
year = {2011},
volume = {117},
pages = {e151--160},
number = {15},
month = apr,
abstract = {Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically
heterogeneous autosomal recessive immune disorder that results when
the critical regulatory pathways that mediate immune defense mechanisms
and the natural termination of immune/inflammatory responses are
disrupted or overwhelmed. To advance the understanding of FHL, we
performed gene expression profiling of peripheral blood mononuclear
cells from 11 children with untreated FHL. Total RNA was isolated
and gene expression levels were determined using microarray analysis.
Comparisons between patients with FHL and normal pediatric controls
(n = 30) identified 915 down-regulated and 550 up-regulated genes
with more than or equal to 2.5-fold difference in expression (P [≤]
.05). The expression of genes associated with natural killer cell
functions, innate and adaptive immune responses, proapoptotic proteins,
and B- and T-cell differentiation were down-regulated in patients
with FHL. Genes associated with the canonical pathways of interleukin-6
(IL-6), IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling
and genes encoding of antiapoptotic proteins were overexpressed in
patients with FHL. This first study of genome-wide expression profiling
in children with FHL demonstrates the complexity of gene expression
patterns, which underlie the immunobiology of FHL.},
comment = {10.1182/blood-2010-08-300046},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/15/e151}
}
@ARTICLE{Sumida2011,
author = {Sumida, Kayo and Igarashi, Yoshinobu and Toritsuka, Naoki and Matsushita,
Tomochika and Abe-Tomizawa, Kaori and Aoki, Mikio and Urushidani,
Tetsuro and Yamada, Hiroshi and Ohno, Yasuo},
title = {Effects of DMSO on gene expression in human and rat hepatocytes},
journal = {Human and Experimental Toxicology},
year = {2011},
volume = {30},
pages = {1701-1709},
number = {10},
abstract = {Dimethyl sulfoxide (DMSO) is a very common organic solvent used for
dissolving lipophilic substances, for example for in vitro cell-based
assays. At the same time, DMSO is known to be cytotoxic at high concentrations.
Therefore, it is important to define threshold concentrations of
DMSO for cells but relevant data at the molecular level are very
limited. We have focused on conducting microarray analyses of human
and rat hepatocytes treated with more than 100 chemicals in attempts
to identify candidate biomarker genes. In the present study, the
effects of DMSO on gene expression and cytotoxicity were assessed
in human cryopreserved hepatocytes and rat primary cultured hepatocytes.
A cytotoxicity test with lactate dehydrogenase (LDH) activity demonstrated
DMSO to be noncytotoxic up to a concentration of 2% (v/v) in both
cases and there were only few effects on the gene expression profiles
up to 0.5% (v/v). The observed differences from controls were considered
to be of little toxicological importance, but still need to be taken
into account in interpretation of findings when DMSO is used at high
concentration.},
doi = {10.1177/0960327111399325},
eprint = {http://het.sagepub.com/cgi/reprint/30/10/1701.pdf},
url = {http://het.sagepub.com/cgi/content/abstract/30/10/1701}
}
@ARTICLE{Summerer2010,
author = {Summerer, Daniel and Schracke, Nadine and Wu, Haiguo and Cheng, Yang
and Bau, Stephan and Stähler, Cord F. and Stähler, Peer F. and Beier,
Markus},
title = {Targeted high throughput sequencing of a cancer-related exome subset
by specific sequence capture with a fully automated microarray platform},
journal = {Genomics},
year = {2010},
volume = {95},
pages = {241--246},
number = {4},
month = apr,
abstract = {Sequence capture methods for targeted next generation sequencing promise
to massively reduce cost of genomics projects compared to untargeted
sequencing. However, evaluated capture methods specifically dedicated
to biologically relevant genomic regions are rare. Whole exome capture
has been shown to be a powerful tool to discover the genetic origin
of disease and provides a reduction in target size and thus calculative
sequencing capacity of > 90-fold compared to untargeted whole genome
sequencing. For further cost reduction, a valuable complementing
approach is the analysis of smaller, relevant gene subsets but involving
large cohorts of samples. However, effective adjustment of target
sizes and sample numbers is hampered by the limited scalability of
enrichment systems. We report a highly scalable and automated method
to capture a 480 Kb exome subset of 115 cancer-related genes using
microfluidic DNA arrays. The arrays are adaptable from 125 Kb to
1 Mb target size and/or one to eight samples without barcoding strategies,
representing a further 26 - 270-fold reduction of calculative sequencing
capacity compared to whole exome sequencing. Illumina GAII analysis
of a HapMap genome enriched for this exome subset revealed a completeness
of > 96%. Uniformity was such that > 68% of exons had at least half
the median depth of coverage. An analysis of reference SNPs revealed
a sensitivity of up to 93% and a specificity of 98.2% or higher.},
issn = {0888-7543},
keywords = {Exome Sequencing, Genomics, Next-Generation Sequencing, Sequence capture,
Microarrays, Microfluidics},
url = {http://www.sciencedirect.com/science/article/B6WG1-4YB5M2P-1/2/6b0ba4bf9fecd042d38037e952c83ebc}
}
@ARTICLE{Summerer2009,
author = {Summerer, Daniel and Wu, Haiguo and Haase, Bettina and Cheng, Yang
and Schracke, Nadine and Stahler, Cord F. and Chee, Mark S. and Stahler,
Peer F. and Beier, Markus},
title = {Microarray-based multicycle-enrichment of genomic subsets for targeted
next-generation sequencing},
journal = {Genome Res.},
year = {2009},
volume = {19},
pages = {1616--1621},
number = {9},
month = sep,
abstract = {The lack of efficient high-throughput methods for enrichment of specific
sequences from genomic DNA represents a key bottleneck in exploiting
the enormous potential of next-generation sequencers. Such methods
would allow for a systematic and targeted analysis of relevant genomic
regions. Recent studies reported sequence enrichment using a hybridization
step to specific DNA capture probes as a possible solution to the
problem. However, so far no method has provided sufficient depths
of coverage for reliable base calling over the entire target regions.
We report a strategy to multiply the enrichment performance and consequently
improve depth and breadth of coverage for desired target sequences
by applying two iterative cycles of hybridization with microfluidic
Geniom biochips. Using this strategy, we enriched and then sequenced
the cancer-related genes BRCA1 and TP53 and a set of 1000 individual
dbSNP regions of 500 bp using Illumina technology. We achieved overall
enrichment factors of up to 1062-fold and average coverage depths
of 470-fold. Combined with high coverage uniformity, this resulted
in nearly complete consensus coverages with >86% of target region
covered at 20-fold or higher. Analysis of SNP calling accuracies
after enrichment revealed excellent concordance, with the reference
sequence closely mirroring the previously reported performance of
Illumina sequencing conducted without sequence enrichment.},
url = {http://genome.cshlp.org/cgi/content/abstract/19/9/1616}
}
@ARTICLE{Sun2011e,
author = {Sun, Bing and Zhang, Feng and Wu, Shi-kai and Guo, Xiaohong and Zhang,
Li-li and Jiang, Ze-fei and Wang, Duen-mei and Song, San-tai},
title = {Gene Expression Profiling for Breast Cancer Prognosis in Chinese
Populations},
journal = {The Breast Journal},
year = {2011},
volume = {17},
pages = {172--179},
number = {2},
abstract = {Abstract:  To investigate a quantitative reverse transcription polymerase
chain reaction (QRT-PCR) assay different from 21-gene assay which
can be used to prognosticate the risk of recurrence in patients with
estrogen receptor (ER) positive, lymph node (LN) negative breast
cancer. To accurately determine the relationship between the Recurrence
Score (RS) derived from our assay and the risk of distant recurrence
in Chinese patients with LN negative and positive breast cancer through
the analysis of paraffin tissues. We obtained archival paraffin-embedded
tissues from patients with invasive breast cancer and varying axillary
lymph node involvement. QRT-PCR reaction was performed by using the
method of SYBR Green I dye with primers. Expression of the 21-genes
was converted to RS by a prespecified algorithm. We then assessed
the probability of the test to accurately predict distant recurrence-free
survival in this retrospective cohort. Ninety-three patients were
eligible based on gene expression profiles. In our population, most
breast cancer patients were premenopausal (82.6%), at early stage
(93.6%) and ER positive (91.4%). Median follow-up was 65.9Â months.
The 5-year recurrence-free survival rate for the group was 58.8%.
The concordance between the reverse transcription-PCR and immunohistochemical
(IHC) measurement for ER, progesterone receptor (PgR), and HER-2
determinations was high and comparable. High RS was predictive of
an elevated risk of relapse (p < 0.001). In subgroups of patients,
RS had significantly predictive performance both in node-negative
(p = 0.009) and node-positive patients (p = 0.038). Multivariable
analysis showed that nodal status, adjuvant hormonal therapy and
RS were significantly related to prognosis. RS category is a better
predictor than the other risk assessment criteria or clinicopatholic
features, with which we can determine more accurately the risks for
recurrence of various patients. We have established an easy and economical
QRT-PCR assay and validated in concordance with IHC measurements
for ER, PgR, and HER-2. RS was associated with distant recurrence
among Chinese patients with hormone receptor (HR) positive breast
cancer. This study may promote the use of RS estimated from the expression
of the 21-gene set for prognostication and routine clinical diagnostic
application in Chinese populations.},
doi = {10.1111/j.1524-4741.2010.01049.x},
issn = {1524-4741},
keywords = {breast cancer, gene expression, paraffin-embedded tissues, real-time
reverse transcription polymerase chain reaction},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1524-4741.2010.01049.x}
}
@ARTICLE{Sun2010c,
author = {Sun, Chuan Bao and Du, Xian Ming and He, Yu Ke},
title = {A novel method for constructing pathogen-regulated small RNA cDNA
library},
journal = {Biochemical and Biophysical Research Communications},
year = {2010},
volume = {397},
pages = {532--536},
number = {3},
month = jul,
abstract = {Pathogen-responsive endogenous small non-coding RNAs regulate gene
expression in relation to plant immune responses by serving as RNA
silencing machinery. Decay caused by the bacterium, Erwinia carotovora
subsp. carotovora (Ecc), often leads to soft rot disease in the plant
Brassica campestris L. ssp. pekinensis (Bcp). To discover endogenous
small RNA species in Bcp in response to Ecc infection, we developed
a highly efficient approach for cloning pathogen-regulated small
RNAs. A group of degenerate stem-loop reverse primers was designed
to synthesize first single-stranded cDNA (sscDNA) and the sscDNA
was then tailed with a poly(C) at its 3' end to create a forward
priming site. A novel cDNA/RNA subtractive hybridization was performed
to capture Ecc-regulated small RNAs and this subsequently allowed
construction of small RNA cDNA libraries for sequencing.},
issn = {0006-291X},
keywords = {Small non-coding RNA, cDNA/RNA subtractive hybridization, Stem-loop
primer},
url = {http://www.sciencedirect.com/science/article/B6WBK-506J3M6-F/2/35e1e689070c513816a0c41138a58f09}
}
@ARTICLE{Sun2006,
author = {Sun, Chi-Chin and Su Pang, Jong-Hwei and Cheng, Ching-Yi and Cheng,
Hsiao-Fen and Lee, Yun-Shien and Ku, Wan-Chen and Hsiao, Ching-Hsi
and Chen, Jen-Kan and Yang, Chuen-Mao},
title = {Interleukin-1 Receptor Antagonist (IL-1RA) Prevents Apoptosis in
Ex Vivo Expansion of Human Limbal Epithelial Cells Cultivated on
Human Amniotic Membrane},
journal = {STEM CELLS},
year = {2006},
volume = {24},
pages = {2130--2139},
number = {9},
abstract = {Abstract 10.1634/stemcells.2005-0590.abs Stem cells of the corneal
epithelium have been found to be located exclusively at the anatomical
junction between the cornea and the conjunctiva, the limbus. Ex vivo
expanded limbal epithelial cells on amniotic membrane (AM) are capable
of restoring the corneal surface with limbal stem cell deficiency.
Recent studies indicate that intact AM preserves the limbal epithelial
phenotype and that distinct epithelial morphology is noted among
various culture matrix. However, the factors in response to the interaction
between limbal epithelial cells and AM were not well understood.
Using Annexin V-fluorescein isothiocyanate staining, we found that
human limbal epithelial cells expanded on intact human AM demonstrated
fewer apoptotic cells as compared with those on plastic dishes. To
identify the anti-apoptotic factors, we performed cDNA microarray
analysis and showed that interleukin-1 receptor antagonist (IL-1RA)
was overexpressed in cultures on intact AM, which was confirmed by
reverse transcription-polymerase chain reaction (RT-PCR), real-time
quantitative PCR (Q-PCR) and enzyme-linked immunosorbent assay. In
addition, we also noted that the phenomenon of apoptosis detected
in cultures on plastic dishes could be reversed by adding recombinant
IL-1RA protein into the media, whereas apoptosis of limbal epithelial
cells cultivated on intact AM could be induced by exogenous neutralizing
IL-1RA neutralizing antibody. These results demonstrated that intact
human AM may prevent cultured human limbal epithelial cells from
undergoing apoptosis. IL-1RA might be a candidate mediator to exert
as an anti-apoptotic molecule during the interaction between human
limbal epithelial cells and intact human AM.},
issn = {1549-4918},
keywords = {Limbal epithelial cells, Amniotic membrane, Interleulin-1 receptor
antagonist, Cytokines, Extracellular matrix},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2005-0590}
}
@ARTICLE{Sun2010a,
author = {Sun, Dong and Yang, Yang-Ming and Jiang, Houli and Wu, Hongyan and
Ojaimi, Caroline and Kaley, Gabor and Huang, An},
title = {Roles of CYP2C29 and RXR{gamma} in vascular EET synthesis of female
mice},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2010},
volume = {298},
pages = {R862--869},
number = {4},
month = apr,
abstract = {We aimed to identify which cytochrome P-450 (CYP) family/subfamily,
as well as related transcription factor(s), is responsible for the
estrogen-dependent synthesis of epoxyeicosatrienoic acids (EETs)
to initiate shear stress-induced vasodilation. Microarray analysis
indicated a significant upregulation of CYP2C29 and retinoid X receptor
{gamma} (RXR{gamma}) in isolated mesenteric arteries/arterioles of
female endothelial nitric oxide synthase-knockout mice, a result
that was validated by real-time RT-PCR. The cannulated vessels were
then perfused with 2 and 10 dyn/cm2 shear stress, followed by collection
of the perfusate to determine EET concentrations and isoforms. Shear
stress dose-dependently stimulated the release of EETs into the perfusate,
associated with an EET-mediated vasodilation, in which predominantly
14,15-EET and 11,12-EET contributed to the responses ([~]87.4% of
total EETs). Transfection of vessels with CYP2C29 siRNA eliminated
the release of EETs into the perfusate, which was evidenced by an
abolished vasodilation, and confirmed by RT-PCR and Western blot
analyses. Knockdown of RXR{gamma} in these vessels significantly
inhibited the production of EETs, parallel to a reduced vasodilation.
RXR{gamma} siRNA not only silenced the vascular RXR{gamma} expression,
but synchronously downregulated CYP2C29 expression, leading to a
reduced EET synthesis. In conclusion, our data provide the first
evidence for a specific signaling cascade, by which estrogen potentially
activates the CYP2C29 gene in the absence of nitric oxide, to synthesize
EETs in response to shear stress, via an RXR{gamma}-related regulatory
mechanism.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/298/4/R862}
}
@ARTICLE{Sun2006a,
author = {Sun, Guobin and Thai, Sheau-Fung and Lambert, Guy R. and Wolf, Douglas
C. and Tully, Douglas B. and Goetz, Amber K. and George, Michael
H. and Grindstaff, Rachel D. and Dix, David J. and Nesnow, Stephen},
title = {Fluconazole-induced hepatic cytochrome P450 gene expression and enzymatic
activities in rats and mice},
journal = {Toxicology Letters},
year = {2006},
volume = {164},
pages = {44--53},
number = {1},
month = jun,
abstract = {This study was undertaken to examine the effects of the triazole antifungal
agent fluconazole on the expression of hepatic cytochrome P450 (Cyp)
genes and the activities of Cyp enzymes in male Sprague-Dawley rats
and male CD-1 mice. Alkoxyresorufin O-dealkylation (AROD) methods
were used as measures of Cyp enzyme activities. Western analyses
identified specific Cyp isoforms. Quantitative real-time reverse-transcription
polymerase chain reaction (quantitative real time-RT-PCR) assays
were used to quantitate the mRNA expression of specific Cyp genes
induced by this conazole. Rats and mice were administered fluconazole
2, 25, or 50 mg/kg bw/d by gavage daily for 14 days. In rats, fluconazole
treatment (50 mg/kg bw/d) significantly induced pentoxyresorufin
O-dealkylation (PROD), benzyloxyresorufin O-dealkylation (BROD),
and ethoxyresorufin O-dealkylation (EROD) hepatic microsomal activities.
Fluconazole treatment significantly increased rat hepatic mRNA expression
of CYP2B1 and CYP3A23/3A1 with dose-related responses. The highest
dose of fluconazole gave a 128-fold induction of CYP2B1 and a 4.6-fold
induction of CYP3A23/3A1 mRNA. CYP3A2 mRNA levels were also overexpressed
5.6-7.2-fold depending on dose. Western immunoblots of rat hepatic
microsomal proteins identified Cyp isoforms: CYP1A1, CYP1A2, CYP2B1/2,
CYP3A23/3A1, and Cyp3A2 with increased levels of CYP2B1/2 and CYP3A23/3A1
proteins. In mice, fluconazole induced BROD, PROD, EROD, and methoxyresorufin
O-dealkylation hepatic microsomal activities after treatment with
25 and 50 mg/kg bw/d. Fluconazole increased mouse hepatic mRNA expression
of Cyp2b10 (1.9-fold) and Cyp3a11 (2.6-fold) in the 50 mg/kg bw/d
treatment group. In summary, these results indicated that fluconazole,
a triazole-containing conazole, clearly induced CYP2B and CYP3A families
of isoforms in rat liver and Cyp2b and Cyp3a families of isoforms
in mouse liver.},
issn = {0378-4274},
keywords = {Fluconazole, PCR, P450, Cyp, Alkoxyresorufin O-dealkylation, Western},
url = {http://www.sciencedirect.com/science/article/B6TCR-4J021PS-2/2/8f225827fcc402afcb63e4b36d3d7208}
}
@ARTICLE{Sun2005,
author = {Sun, Guobin and Thai, Sheau-Fung and Tully, Douglas B. and Lambert,
Guy R. and Goetz, Amber K. and Wolf, Douglas C. and Dix, David J.
and Nesnow, Stephen},
title = {Propiconazole-induced cytochrome P450 gene expression and enzymatic
activities in rat and mouse liver},
journal = {Toxicology Letters},
year = {2005},
volume = {155},
pages = {277--287},
number = {2},
month = feb,
abstract = {Propiconazole is a N-substituted triazole used as a fungicide on fruits,
grains, seeds, hardwoods, and conifers. In the present study, propiconazole
was examined for its effects on the expression of hepatic cytochrome
P450 genes and on the activities of P450 enzymes in male Sprague-Dawley
rats and male CD-1 mice. Rats and mice were administered propiconazole
by gavage daily for 14 days at doses of 10, 75, and 150 mg/kg body
weight/day. Quantitative real time RT-PCR assays of rat hepatic RNA
samples from animals treated at the 150 mg/kg body weight/day dose
revealed significant mRNA overexpression of the following genes compared
to control: CYP1A2 (1.62-fold), CYP2B1 (10.8-fold), CYP3A1/CYP3A23
(2.78-fold), and CYP3A2 (1.84-fold). In mouse liver, propiconazole
produced mRNA overexpression of Cyp2b10 (2.39-fold) and Cyp3a11 (5.19-fold).
mRNA expression of CYP1A1 was not detected in liver tissues from
treated or controls animals from either species. Propiconazole significantly
induced both pentoxyresorufin O-dealkylation (PROD) and methoxyresorufin
O-dealkylation (MROD) activities in both rat and mouse liver at the
150 mg/kg body weight/day and 75 mg/kg body weight/day doses. In
summary, these results indicated that propiconazole induced CYP1A2
in rat liver and CYP2B and CYP3A families of isoforms in rat and
mouse liver.},
issn = {0378-4274},
keywords = {Propiconazole, PCR, P450, Alkoxyresorufin O-dealkylation, Gene expression
quantitative real-time RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6TCR-4DW8YH6-2/2/35e2a53d7c47cbcfa9bce679c7f8971c}
}
@ARTICLE{Sun2008,
author = {Sun, Hongxia and Chung, Wen-Cheng and Ryu, Seung-Hee and Ju, Zhenlin
and Tran, Hai T. and Kim, Edward and Kurie, Jonathan M. and Koo,
Ja Seok},
title = {Cyclic AMP-Responsive Element Binding Protein- and Nuclear Factor-{kappa}B-Regulated
CXC Chemokine Gene Expression in Lung Carcinogenesis},
journal = {Cancer Prevention Research},
year = {2008},
volume = {1},
pages = {316--328},
number = {5},
month = oct,
abstract = {The recognition of the importance of angiogenesis in tumor progression
has led to the development of antiangiogenesis as a new strategy
for cancer treatment and prevention. By modulating tumor microenvironment
and inducing angiogenesis, the proinflammatory cytokine interleukine
(IL)-1{beta} has been reported to promote tumor development. However,
the factors mediating IL-1{beta}-induced angiogenesis in non-small
cell lung cancer (NSCLC) and the regulation of these angiogenic factors
by IL-1{beta} are less clear. Here, we report that IL-1{beta} up-regulated
an array of proangiogenic CXC chemokine genes in the NSCLC cell line
A549 and in normal human tracheobronchial epithelium cells, as determined
by microarray analysis. Further analysis revealed that IL-1{beta}
induced much higher protein levels of CXC chemokines in NSCLC cells
than in normal human tracheobronchial epithelium cells. Conditioned
medium from IL-1{beta}-treated A549 cells markedly increased endothelial
cell migration, which was suppressed by neutralizing antibodies against
CXCL5 and CXCR2. We also found that IL-1{beta}-induced CXC chemokine
gene overexpression in NSCLC cells was abrogated with the knockdown
of cyclic AMP-responsive element binding protein (CREB) or nuclear
factor {kappa}B (NF-{kappa}B). Moreover, the expression of the CXC
chemokine genes as well as CREB and NF-{kappa}B activities was greatly
increased in the tumorigenic NSCLC cell line compared with normal,
premalignant immortalized or nontumorigenic cell lines. A disruptor
of the interaction between CREB-binding protein and transcription
factors such as CREB and NF-{kappa}B, 2-naphthol-AS-E-phosphate (KG-501),
inhibited IL-1{beta}-induced CXC chemokine gene expression and angiogenic
activity in NSCLC. We propose that targeting CREB or NF-{kappa}B
using small-molecule inhibitors, such as KG-501, holds promise as
a preventive and/or therapeutic approach for NSCLC.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/1/5/316}
}
@ARTICLE{Sun2004,
author = {Sun, Jiying and Brand, Marjorie and Zenke, Yukari and Tashiro, Satoshi
and Groudine, Mark and Igarashi, Kazuhiko},
title = {Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors
in the Maf transcription factor network},
journal = {PNAS},
year = {2004},
volume = {101},
pages = {1461--1466},
number = {6},
month = feb,
abstract = {Small Maf proteins serve as dual-function transcription factors through
an exchange of their heterodimerization partners. For example, as
heterodimers with hematopoietic cell-specific p45 NF-E2 or NF-E2-related
factors (Nrf), they activate the {beta}-globin or antioxidative stress
enzyme heme oxygenase 1 (HO-1) genes, respectively. In contrast,
together with Bach1, they repress these same genes. However, the
signals leading to this partner exchange are not known. Using chromatin
immunoprecipitation assays in NIH 3T3 cells, we show that heme, an
inducer of ho-1, promotes displacement of Bach1 from the MafK-occupied
ho-1 enhancers, which is followed by Nrf2 binding to these elements.
Whereas histone H3 at the ho-1 enhancers and promoter is hyperacetylated
irrespective of gene activity, exposure of cells to heme results
in de novo hyperacetylation and hypermethylation of histone H3 in
the transcribed region. These data indicate that, under normal conditions,
the chromatin structure of ho-1 is in a preactivation state, but
transcription is repressed by Bach1. Heme induces switching of Maf
dimers, resulting in ho-1 expression. Heme also promotes displacement
of Bach1 from the {beta}-globin locus control region without affecting
MafK binding in murine erythroleukemia cells. Thus, heme functions
as a signaling molecule for gene expression in higher eukaryotes.},
url = {http://www.pnas.org/cgi/content/abstract/101/6/1461}
}
@ARTICLE{Sun2010b,
author = {Sun, Jianlong and Li, Rong},
title = {Human Negative Elongation Factor Activates Transcription and Regulates
Alternative Transcription Initiation},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {6443--6452},
number = {9},
month = feb,
abstract = {The human negative elongation factor (NELF) is a four-subunit protein
complex that inhibits the movement of RNA polymerase II (RNAPII)
at an early elongation stage in vitro. NELF-mediated stalling of
RNAPII also attenuates transcription of a number of inducible genes
in human cells. To obtain a genome-wide understanding of human NELF-mediated
transcriptional regulation in vivo, we carried out an exon array
study in T47D breast cancer cells with transient small interfering
RNA knockdown of individual NELF subunits. Upon depletion of NELF-A,
-C, or -E, the vast majority of NELF-regulated genes were down-regulated.
Many of the down-regulated genes encode proteins that play key roles
in cell cycle progression. Consequently, NELF knockdown resulted
in significant reduction in DNA synthesis and cell proliferation.
Chromatin immunoprecipitation showed that NELF knockdown led to dissociation
of RNAPII from the promoter-proximal region of the cell cycle-regulating
genes. This was accompanied by decreased histone modifications associated
with active transcription initiation (H3K9Ac) and elongation (H3K36Me3),
as well as reduced recruitment of the general transcription factor
TFIIB and increased overall histone occupancy at a subset of the
down-regulated promoters. Lastly, our study indicates that NELF regulates
alternative transcription initiation of BSG (Basigin) gene by differentially
influencing RNAPII density at the two neighboring exons at the 5'
end of the gene. Taken together, our data suggest a diverse transcriptional
consequence of NELF-mediated RNAPII pausing in the human genome.},
url = {http://www.jbc.org/cgi/content/abstract/285/9/6443}
}
@ARTICLE{Sun2009,
author = {Sun, Liou and Sadighi Akha, Amir A. and Miller, Richard A. and Harper,
James M.},
title = {Life-Span Extension in Mice by Preweaning Food Restriction and by
Methionine Restriction in Middle Age},
journal = {J Gerontol A Biol Sci Med Sci},
year = {2009},
volume = {64A},
pages = {711--722},
number = {7},
month = jul,
abstract = {Life span can be extended in rodents by restricting food availability
(caloric restriction [CR]) or by providing food low in methionine
(Meth-R). Here, we show that a period of food restriction limited
to the first 20 days of life, via a 50% enlargement of litter size,
shows extended median and maximal life span relative to mice from
normal sized litters and that a Meth-R diet initiated at 12 months
of age also significantly increases longevity. Furthermore, mice
exposed to a CR diet show changes in liver messenger RNA patterns,
in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation
of mammalian target of rapamycin and its substrate 4EBP1, HE-binding
protein 1 that are not observed in liver from age-matched Meth-R
mice. These results introduce new protocols that can increase maximal
life span and suggest that the spectrum of metabolic changes induced
by low-calorie and low-methionine diets may differ in instructive
ways.},
url = {http://biomedgerontology.oxfordjournals.org/cgi/content/abstract/64A/7/711}
}
@ARTICLE{Sun2006b,
author = {Sun, Liwen and Wang, Li and Sun, Yong and Tang, Syao-wei and Hu,
Yinghe},
title = {Protective effects of EUK4010 on β-amyloid(1–42) induced degeneration
of neuronal cells},
journal = {European Journal of Neuroscience},
year = {2006},
volume = {24},
pages = {1011--1019},
number = {4},
abstract = {Abstract EUK4010 has been identified to exhibit an inhibitory effect
on β-amyloid (Aβ)1−42-induced loss of neuronal cell viability.
Further studies demonstrated that EUK4010 attenuated the Aβ1−42-induced
degeneration in both cultured rat hippocampal neurons and human neuroblastoma
cells, as demonstrated by typical morphological changes, cell viability
and the chip-based flow cytometric assay. Gene expression analysis
using DNA microarray showed that the senescence marker calcium-binding
protein, regucalcin (Rgn), GABA-A receptor pi subunit (Gabrp), the
huntingtin binding protein, optineurin (Optn) and a semaphorin family
plexin A3 similar protein (Plex-similar) changed their expression
levels significantly in cultured neurons after Aβ1−42 treatment.
In this report, we have undertaken a chemical genetic approach to
study the molecular basis of Aβ1−42 effects on the neuronal degeneration.
Our results demonstrate that EUK4010 completely blocked the Aβ1−42-induced
up-regulation of GABA-A receptor pi subunit and the semaphorin family
plexin A3 similar protein, and partially attenuated the down-regulation
of senescence marker calcium-binding protein, regucalcin. These observations
suggest that EUK4010 may prevent or reduce the Aβ toxicity by regulating
the expression of genes involved in the Aβ induced neuronal degeneration.
These genes may represent a promising target for the therapeutic
drug development for Alzheimer's disease (AD) and other neurological
disorders. Furthermore, EUK4010 and its analogues could potentially
be developed as neuronal protective agents for the treatment of these
diseases.},
issn = {1460-9568},
keywords = {Alzheimer's disease, amyloid-beta1−42, chemical genetics, EUK4010,
neuronal degeneration},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2006.04951.x}
}
@ARTICLE{Sun2008a,
author = {Sun, Michael and Estrov, Zeev and Ji, Yuan and Coombes, Kevin R.
and Harris, David H. and Kurzrock, Razelle},
title = {Curcumin (diferuloylmethane) alters the expression profiles of microRNAs
in human pancreatic cancer cells},
journal = {Mol. Cancer Ther.},
year = {2008},
volume = {7},
pages = {464--473},
number = {3},
month = mar,
abstract = {Background: A major challenge in cancer chemotherapy has been developing
safe and clinically efficacious chemotherapeutic agents. With its
low toxicity profile, curcumin (diferuloylmethane), a naturally occurring
flavinoid derived from the rhizome of Curcuma longa, has great promise.
In vitro and in vivo preclinical studies have shown its inhibitory
anticancer, antioxidant, anti-inflammatory, antiproliferative, and
proapoptotic activities. The multiple mechanisms of the antitumor
effect of curcumin putatively include down-regulating the expression
of gene products such as nuclear factor-{kappa}B, growth suppression,
inducing apoptosis, and modulating various signal transduction pathways
and the expression of many oncogenes. The mechanisms underlying the
antitumor activity of curcumin have not, however, been completely
delineated. Methods: An oligonucleotide microarray chip was developed
and used to profile microRNA (miRNA) expressions in pancreatic cells
treated with curcumin. Transcripts with regulated expression patterns
on the arrays were validated by real-time PCRs. Additionally, potential
mRNA targets were analyzed bioinformatically and confirmed with flow
cytometry experiments. Results: Curcumin alters miRNA expression
in human pancreatic cells, up-regulating miRNA-22 and down-regulating
miRNA-199a*, as confirmed by TaqMan real-time PCR. Upregulation of
miRNA-22 expression by curcumin or by transfection with miRNA-22
mimetics in the PxBC-3 pancreatic cancer cell line suppressed expression
of its target genes SP1 transcription factor (SP1) and estrogen receptor
1 (ESR1), while inhibiting miRNA-22 with antisense enhanced SP1 and
ESR1 expression. Conclusions: These observations suggest that modulation
of miRNA expression may be an important mechanism underlying the
biological effects of curcumin. [Mol Cancer Ther 2008;7(3):464-73]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/7/3/464}
}
@ARTICLE{Sun2011,
author = {Sun, Mingyun and Lin, Jennifer S. and Barron, Annelise E.},
title = {Ultrafast, efficient separations of large-sized dsDNA in a blended
polymer matrix by microfluidic chip electrophoresis: A design of
experiments approach},
journal = {ELECTROPHORESIS},
year = {2011},
volume = {32},
pages = {3233--3240},
number = {22},
abstract = {Double-stranded (ds) DNA fragments over a wide size range were successfully
separated in blended polymer matrices by microfluidic chip electrophoresis.
Novel blended polymer matrices composed of two types of polymers
with three different molar masses were developed to provide improved
separations of large dsDNA without negatively impacting the separation
of small dsDNA. Hydroxyethyl celluloses with average molar masses
of ∼27 kDa and ∼1 MDa were blended with a second class of
polymer, high-molar mass (∼7 MDa) linear polyacrylamide. Fast
and highly efficient separations of commercially available DNA ladders
were achieved on a borosilicate glass microchip. A distinct separation
of a 1-kb DNA extension ladder (200–40 000 bp) was completed
in 2 min. An orthogonal design of experiments was used to optimize
experimental parameters for DNA separations over a wide size range.
We find that the two dominant factors are the applied electric field
strength and the inclusion of a high concentration of low-molar mass
polymer in the matrix solution. These two factors exerted different
effects on the separations of small dsDNA fragments below 1 kbp,
medium dsDNA fragments between 1 and 10 kbp, and large dsDNA fragments
above 10 kbp.},
doi = {10.1002/elps.201100260},
issn = {1522-2683},
keywords = {Blended polymer, Chip electrophoresis, Design of experiments, Large
DNA separation},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.201100260}
}
@ARTICLE{Sun2011d,
author = {Sun, Maoyun and Yan, Xinhua and Bian, Yun and Caggiano, Anthony O.
and Morgan, James P.},
title = {Improving murine embryonic stem cell differentiation into cardiomyocytes
with neuregulin-1: differential expression of microRNA},
journal = {Am J Physiol Cell Physiol},
year = {2011},
volume = {301},
pages = {C21-30},
number = {1},
abstract = {Identification of factors that direct embryonic stem (ES) cell (ESC)
differentiation into functional cardiomyocytes is essential for successful
use of ESC-based therapy for cardiac repair. Neuregulin-1 (NRG1)
and microRNA play important roles in the cardiac differentiation
of ESCs. Understanding how NRG1 regulates microRNA will provide new
mechanistic insights into the role of NRG1 on ESCs. It may also lead
to the discovery of novel microRNAs that are important for ESC cardiac
differentiation. The objective of this study was to assess the microRNA
expression profile during NRG1-induced ESC cardiac differentiation.
Murine ESCs were incubated with a recombinant NRG1{beta} or an inhibitor
of ErbB2 or ErbB4 during hanging drop-induced cardiac differentiation.
The expression of cardiac-specific markers and microRNAs was analyzed
by RT-PCR and microRNA array, respectively. We found that the expression
of NRG1 and the ErbB receptors was increased during hanging drop-induced
cardiac differentiation of ESCs. NRG1 stimulation during a specific
developmental window enhanced, while inhibition of the ErbB2 or ErbB4
receptor inhibited, cardiac differentiation of ESCs. NRG1 increased
the expression of mmu-miR-296-3p and mmu-miR-200c*, and decreased
mmu-miR-465b-5p. Inhibition of mmu-miR-296-3p or mmu-miR-200c* decreased,
while inhibition of mmu-miR-465-5p increased, the differentiation
of ESCs into the cardiac lineage. This is the first report demonstrating
that microRNAs are differentially regulated by NRG1-ErbB signaling
during cardiac differentiation of ESCs. This study has also identified
new microRNAs that are important for ESC cardiac differentiation.},
doi = {10.1152/ajpcell.00141.2010},
eprint = {http://ajpcell.physiology.org/cgi/reprint/301/1/C21.pdf},
url = {http://ajpcell.physiology.org/cgi/content/abstract/301/1/C21}
}
@ARTICLE{Sun2005a,
author = {Sun, Michael M. C. and Beam, Kevin S. and Cerveny, Charles G. and
Hamblett, Kevin J. and Blackmore, Richard S. and Torgov, Michael
Y. and Handley, Felicia G. M. and Ihle, Nathan C. and Senter, Peter
D. and Alley, Stephen C.},
title = {Reduction−Alkylation Strategies for the Modification of Specific
Monoclonal Antibody Disulfides},
journal = {Bioconjugate Chemistry},
year = {2005},
volume = {16},
pages = {1282-1290},
number = {5},
note = {PMID: 16173809},
doi = {10.1021/bc050201y},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bc050201y},
url = {http://pubs.acs.org/doi/abs/10.1021/bc050201y}
}
@ARTICLE{Sun2009a,
author = {Sun, Stella and Yi, Xin and Poon, Ronnie and Yeung, Chun and Day,
Philip and Luk, John},
title = {A protein-based set of reference markers for liver tissues and hepatocellular
carcinoma},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {309},
number = {1},
abstract = {BACKGROUND:During the last decade, investigations have focused on
revealing genes or proteins that are involved in HCC carcinogenesis
using either genetic or proteomic techniques. However, these studies
are overshadowed by a lack of good internal reference standards.
The need to identify "housekeeping" markers, whose expression is
stable in various experimental and clinical conditions, is therefore
of the utmost clinical relevance in quantitative studies. This is
the first study employed 2-DE analysis to screen for potential reference
markers and aims to correlate the abundance of these proteins with
their level of transcript expression.METHODS:A Chinese cohort of
224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic,
and 16 normal) was profiled using 2-DE analysis. Expression of the
potential reference markers was confirmed by western blot, immunohistochemistry
and real-time quantitative PCR. geNorm algorithm was employed for
gene stability measure of the identified reference markers.RESULTS:The
expression levels of three protein markers beta-actin (ACTB), heat
shock protein 60 (HSP60), and protein disulphide isomerase (PDI)
were found to be stable using p-values (p > 0.99) as a ranking tool
in all 224 human liver tissues examined by 2-DE analysis. Of high
importance, ACTB and HSP 60 were successfully validated at both protein
and mRNA levels in human hepatic tissues by western blot, immunohistochemistry
and real-time quantitative PCR. In addition, no significant correlation
of these markers with any clinicopathological features of HCC and
cirrhosis was found. Gene stability measure of these two markers
with other conventionally applied housekeeping genes was assessed
by the geNorm algorithm, which ranked ACTB and HSP60 as the most
stable genes among this cohort of clinical samples.CONCLUSION:Our
findings identified 2 reference markers that exhibited stable expression
across human liver tissues with different conditions thus should
be regarded as reliable reference moieties for normalisation of gene
and protein expression in clinical research employing human hepatic
tissues.},
doi = {10.1186/1471-2407-9-309},
issn = {1471-2407},
pubmedid = {19725976},
url = {http://www.biomedcentral.com/1471-2407/9/309}
}
@ARTICLE{Sun2011a,
author = {Sun, Su M. and Dijkstra, Menno K. and Bijkerk, André C. and Brooimans,
Rik A. and Valk, Peter J. M. and Erkeland, Stefan J. and Löwenberg,
Bob and Jongen-Lavrencic, Mojca},
title = {Transition of highly specific microRNA expression patterns in association
with discrete maturation stages of human granulopoiesis},
journal = {British Journal of Haematology},
year = {2011},
volume = {155},
pages = {395--398},
number = {3},
doi = {10.1111/j.1365-2141.2011.08682.x},
issn = {1365-2141},
keywords = {granulocytes, haematopoiesis, gene arrays, gene expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2141.2011.08682.x}
}
@ARTICLE{Sun2008b,
author = {Sun, Xiaocun and Zemel, Michael B.},
title = {Calcitriol and calcium regulate cytokine production and adipocyte-macrophage
cross-talk},
journal = {The Journal of Nutritional Biochemistry},
year = {2008},
volume = {19},
pages = {392--399},
number = {6},
month = jun,
abstract = {Objective The objective of this study was to investigate the effects
of calcitriol on adipocyte and macrophage cytokine expression as
well as release and on adipocyte-macrophage cross-talk in local modulation
of inflammation.Research Procedures and Results We investigated calcitriol
modulation of the expression of macrophage inhibitory factor (MIF)
and macrophage surface-specific protein CD14, two key factors in
regulating macrophage function and survival, in differentiated human
adipocytes. Calcitriol significantly increased MIF and CD14 expression
by 59% and 33%, respectively, while calcium-channel antagonism with
nifedipine completely reversed these effects, indicating that calcitriol
stimulates MIF and CD14 expression via a calcium-dependent mechanism.
Similar results were also found in cultured 3T3-L1 adipocytes; in
addition, calcitriol also up-regulated macrophage colony-stimulating
factor, macrophage inflammatory protein, interleukin-6 (IL-6) as
well as monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes
and stimulated tumor necrosis factor as well as IL-6 expression in
RAW 264 macrophages. These effects were blocked by either a calcium-channel
antagonist (nifedipine) or a mitochondrial uncoupler (dinitrophenol).
Moreover, co-culture of 3T3-L1 adipocytes with RAW 264 macrophages
significantly increased the expression and production of multiple
inflammatory cytokines in response to calcitriol in both cell types.Conclusions
These data demonstrate that calcitriol regulates local inflammation
via modulating the interaction between adipocytes and macrophages
as well as regulating inflammatory cytokine production in each cell
type via calcium-dependent and mitochondrial uncoupling-dependent
mechanisms. These data provide further mechanistic explanation for
our recent observations that suppression of calcitriol by dietary
calcium reduces inflammatory cytokine expression and oxidative stress
in adipose tissue.},
issn = {0955-2863},
keywords = {Calcitriol, Calcium, Adipocyte, Macrophage, Cytokine},
url = {http://www.sciencedirect.com/science/article/B6T8P-4PNF2KX-3/2/273baf7aabf174b5193138e7243f8bd0}
}
@ARTICLE{Sun2011c,
author = {Xianyun Sun and Hanxing Zhang and Zhenying Zhang and Yong Wang and
Shaojie Li},
title = {Involvement of a helix–loop–helix transcription factor CHC-1
in CO2-mediated conidiation suppression in Neurospora crassa},
journal = {Fungal Genetics and Biology},
year = {2011},
volume = {48},
pages = {1077 - 1086},
number = {12},
abstract = {The morphological switch from vegetative growth to conidiation in
filamentous fungi is highly regulated, but the understanding of the
regulatory mechanisms is limited. In this study, by screening a set
of knock-out mutants corresponding to 103 transcription factor encoding
genes in Neurospora crassa, a mutant was found to produce abundant
conidia in race tubes in which conidiation in the wild-type strain
was suppressed. The corresponding gene NCU00749 encodes a protein
containing a helix–loop–helix DNA binding region. Unlike enhanced
conidiation in ras-1 and sod-1 mutants, which was completely suppressed
by antioxidant N-acetyl cysteine, enhanced conidiation in the NCU00749
mutant was only slightly affected by N-acetyl cysteine. When grown
on slants, the NCU00749 deletion mutant exhibited earlier conidial
formation than the wild-type strain, and this was more evident at
a higher (5%) CO2 concentration. Therefore, we named NCU00749 as
conidiation at high carbon dioxide-1 (chc-1). Genes that are highly
expressed during conidial development, eas, con-6, con-8 and con-10,
were transcribed at a higher rate in the chc-1 deletion mutant than
the wild-type strain in response to conidiation induction. To determine
the mechanisms by which CHC-1 regulates conidiation, we conducted
a RNA sequencing analysis and found that 404 genes exhibited ⩾
2 fold changes in transcription in response to chc-1 deletion. Among
them, fluffy and ada-6, two transcription factor genes that positively
regulate conidiation in N. crassa, and rca-1, whose homolog flbD
in Aspergillus nidulans is essential for conidiation, were upregulated
in the chc-1 deletion mutant. Results of RNA sequencing also suggest
that signal transduction via the cAMP and the MAK-2 mediated signal
pathways, and ROS generation and removal, mechanisms known to regulate
conidiation, are not involved in chc-1 mediated control of conidiation.
In addition, chc-1 also influences expression of genes involved in
other important biological processes besides conidiation such as
carbon metabolism, sphingolipid synthesis, cell wall synthesis, and
calcium signaling.},
doi = {10.1016/j.fgb.2011.09.003},
issn = {1087-1845},
keywords = {Conidiation},
url = {http://www.sciencedirect.com/science/article/pii/S1087184511001733}
}
@ARTICLE{Sun2010,
author = {Sun, Yu and Almomani, Rowida and Aten, Emmelien and Celli, Jacopo
and van der Heijden, Jaap and Venselaar, Hanka and Robertson, Stephen
P. and Baroncini, Anna and Franco, Brunella and Basel-Vanagaite,
Lina and Horii, Emiko and Drut, Ricardo and Ariyurek, Yavuz and den
Dunnen, Johan T. and Breuning, Martijn H.},
title = {Terminal Osseous Dysplasia Is Caused by a Single Recurrent Mutation
in the FLNA Gene},
journal = {The American Journal of Human Genetics},
year = {2010},
volume = {87},
pages = {146--153},
number = {1},
month = jul,
abstract = {Terminal osseous dysplasia (TOD) is an X-linked dominant male-lethal
disease characterized by skeletal dysplasia of the limbs, pigmentary
defects of the skin, and recurrent digital fibroma with onset in
female infancy. After performing X-exome capture and sequencing,
we identified a mutation at the last nucleotide of exon 31 of the
FLNA gene as the most likely cause of the disease. The variant c.5217G>A
was found in six unrelated cases (three families and three sporadic
cases) and was not found in 400 control X chromosomes, pilot data
from the 1000 Genomes Project, or the FLNA gene variant database.
In the families, the variant segregated with the disease, and it
was transmitted four times from a mildly affected mother to a more
seriously affected daughter. We show that, because of nonrandom X
chromosome inactivation, the mutant allele was not expressed in patient
fibroblasts. RNA expression of the mutant allele was detected only
in cultured fibroma cells obtained from 15-year-old surgically removed
material. The variant activates a cryptic splice site, removing the
last 48 nucleotides from exon 31. At the protein level, this results
in a loss of 16 amino acids (p.Val1724_Thr1739del), predicted to
remove a sequence at the surface of filamin repeat 15. Our data show
that TOD is caused by this single recurrent mutation in the FLNA
gene.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-50F4J67-8/2/5bf3d40e77e6da7bfcdeae5a8c145556}
}
@ARTICLE{Sun2006c,
author = {Sun, Yi and Boyd, Kelli and Xu, Wu and Ma, Jing and Jackson, Carl
W. and Fu, Amina and Shillingford, Jonathan M. and Robinson, Gertraud
W. and Hennighausen, Lothar and Hitzler, Johann K. and Ma, Zhigui
and Morris, Stephan W.},
title = {Acute Myeloid Leukemia-Associated Mkl1 (Mrtf-a) Is a Key Regulator
of Mammary Gland Function},
journal = {Mol. Cell. Biol.},
year = {2006},
volume = {26},
pages = {5809--5826},
number = {15},
month = aug,
abstract = {Transcription of immediate-early genes--as well as multiple genes
affecting muscle function, cytoskeletal integrity, apoptosis control,
and wound healing/angiogenesis--is regulated by serum response factor
(Srf). Extracellular signals regulate Srf in part via a pathway involving
megakaryoblastic leukemia 1 (Mkl1, also known as myocardin-related
transcription factor A [Mrtf-a]), which coactivates Srf-responsive
genes downstream of Rho GTPases. Here we investigate Mkl1 function
using gene targeting and show the protein to be essential for the
physiologic preparation of the mammary gland during pregnancy and
the maintenance of lactation. Lack of Mkl1 causes premature involution
and impairs expression of Srf-dependent genes in the mammary myoepithelial
cells, which control milk ejection following oxytocin-induced contraction.
Despite the importance of Srf in multiple transcriptional pathways
and widespread Mkl1 expression, the spectrum of abnormalities associated
with Mkl1 absence appears surprisingly restricted.},
url = {http://mcb.asm.org/cgi/content/abstract/26/15/5809}
}
@ARTICLE{Sun2011f,
author = {Sun, Yi and Dhumpa, Raghuram and Bang, Dang Duong and Handberg, Kurt
and Wolff, Anders},
title = {DNA microarray-based solid-phase RT-PCR for rapid detection and identification
of influenza virus type A and subtypes H5 and H7},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2011},
volume = {69},
pages = {432--439},
number = {4},
month = apr,
abstract = {Endemic of avian influenza virus (AIV) in Asia and epizootics in some
European regions have caused considerable public concern on a possible
pandemic of AIV. A rapid method for virus detection and effective
surveillance in wild avian, poultry production as well as in humans
is required. In this article, a DNA microarray-based solid-phase
polymerase chain reaction (PCR) approach has been developed for rapid
detection of influenza virus type A and for simultaneous identification
of pathogenic virus subtypes H5 and H7. This solid-phase RT-PCR method
combined reverse-transcription amplification of RNA extract in the
liquid phase with sequence-specific nested PCR on the solid phase.
A simple ultraviolet cross-linking method was used to immobilize
the DNA probes over an unmodified glass surface, which makes solid-phase
PCR a convenient possibility for AIV screening. The testing of 33
avian fecal and tracheal swab specimens was completed in less than
2 h with 94% accuracy.},
issn = {0732-8893},
keywords = {Avian influenza virus, Solid-phase RT-PCR, DNA microarray},
url = {http://www.sciencedirect.com/science/article/pii/S0732889310005420}
}
@ARTICLE{Sun2011b,
author = {Yunguang Sun and Siyuan Zheng and Artour Torossian and Christina
K. Speirs and Stephen Schleicher and Nicholas J. Giacalone and David
P. Carbone and Zhongming Zhao and Bo Lu},
title = {Role of Insulin-Like Growth Factor-1 Signaling Pathway in Cisplatin-Resistant
Lung Cancer Cells},
journal = {International Journal of Radiation Oncology*Biology*Physics},
year = {2011},
pages = { - },
number = {0},
abstract = {Purpose The development of drug-resistant phenotypes has been a major
obstacle to cisplatin use in non–small-cell lung cancer. We aimed
to identify some of the molecular mechanisms that underlie cisplatin
resistance using microarray expression analysis. Methods and Materials
H460 cells were treated with cisplatin. The differences between cisplatin-resistant
lung cancer cells and parental H460 cells were studied using Western
blot, MTS, and clonogenic assays, in vivo tumor implantation, and
microarray analysis. The cisplatin-R cells were treated with human
recombinant insulin-like growth factor (IGF) binding protein-3 and
siRNA targeting IGF-1 receptor. Results Cisplatin-R cells illustrated
greater expression of the markers CD133 and aldehyde dehydrogenase,
more rapid in vivo tumor growth, more resistance to cisplatin- and
etoposide-induced apoptosis, and greater survival after treatment
with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R
demonstrated decreased expression of insulin-like growth factor binding
protein-3 and increased activation of IGF-1 receptor signaling compared
with parental H460 cells in the presence of IGF-1. Human recombinant
IGF binding protein-3 reversed cisplatin resistance in cisplatin-R
cells and targeting of IGF-1 receptor using siRNA resulted in sensitization
of cisplatin-R-cells to cisplatin and radiation. Conclusions The
IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and
radiation. Thus, this pathway represents a potential target for improved
lung cancer response to treatment.},
doi = {10.1016/j.ijrobp.2011.06.1999},
issn = {0360-3016},
keywords = {Cisplatin resistance},
url = {http://www.sciencedirect.com/science/article/pii/S0360301611029300}
}
@ARTICLE{Sundstroem2010,
author = {Sundström, Mia and Lejon, Kristina},
title = {The prolonged and enhanced immune response in the non-obese diabetic
mouse is dependent on genes in the Idd1/24, Idd12 and Idd18 regions},
journal = {Journal of Autoimmunity},
year = {2010},
volume = {35},
pages = {375--382},
number = {4},
month = dec,
abstract = {In non-obese diabetic (NOD) mice B cells are an absolute requirement
for T1D development. NOD mice display various B cell related immune
deviations when compared to normal mice such as an enhanced and prolonged
immune response towards several antigens, including non-self immunoglobulins.
We hypothesized that this trait contributes to diabetes pathogenesis,
and investigated the genetic factor(s) governing the altered immune
response. A (NODxC57BL/6)F2 cohort (n = 214) were analyzed for its
primary immune response against a BALB/c derived monoclonal antibody,
and a genome wide linkage analysis was performed. Significant linkage
to the Idd1/Idd24, Idd12 and Idd18.1 regions as well as to a proximal
region (marker D2Mit367, 33.5 Mb) on chromosome 2 was detected. We
verified the observed linkage by analyzing a set of H2 congenic NOD
and C57BL/6 mice and narrowed down the region to 8 Mb. Interaction
between Idd1/24 and Idd12, as well as the novel locus on chromosome
2 was observed. However, the action by Idd18.1 was not influenced
by any of the other loci. In addition to the known H2 I-A[beta]g7
allelic variant of Idd1 in NOD, candidate gene analysis revealed
a significant difference in the transcription of the H2-O/DO molecule.
We hypothesize that multiple mechanisms contribute to the loss of
immune response control, including that peptide loading on MHC class
II in B cells of NOD is altered.},
issn = {0896-8411},
keywords = {NOD, Idd, B cell, Immune response, H2-O},
url = {http://www.sciencedirect.com/science/article/B6WHC-511H39V-1/2/3c1efe425b93bbb262b6d60a34c6633c}
}
@ARTICLE{Sundvold2011,
author = {Sundvold, Hilde and Helgeland, Hanna and Baranski, Matthew and Omholt,
Stig and Vage, Dag},
title = {Characterisation of a novel paralog of scavenger receptor class B
member I (SCARB1) in Atlantic salmon (Salmo salar)},
journal = {BMC Genetics},
year = {2011},
volume = {12},
pages = {52},
number = {1},
abstract = {BACKGROUND:Red flesh colour is a unique trait found in some salmonid
genera. Carotenoid pigments are not synthesized de novo in the fish,
but are provided by dietary uptake. A better understanding of the
molecular mechanisms underlying the cellular uptake and deposition
of carotenoids could potentially be used to improve the low muscle
deposition rate that is typically found in farmed Atlantic salmon.
In addition, from an evolutionary point of view, the establishment
and maintenance of this trait is still poorly understood. It has
been demonstrated in several species that scavenger receptor class
B, member 1 (SCARB1) is involved in intestinal absorption of carotenoids,
which makes this gene a possible source of genetic variation in salmonid
flesh pigmentation.RESULTS:In this study, a novel paralog of SCARB1
(SCARB1-2) was detected through screening for genetic variation in
Atlantic salmon SCARB1. Full length SCARB1-2 encodes a protein with
89% identity to Atlantic salmon SCARB1, except for the C-terminal
cytoplasmic tail that shows only 12% identity. The most prominent
site of SCARB1 mRNA expression was in the mid gut, while a five-fold
lower level was detected in Atlantic salmon skeletal muscle and liver.
The SCARB1-2 mRNA was equally expressed in liver, muscle and mid
gut, and at a lower level than SCARB1 mRNA. A total of seven different
SCARB1-2 alleles comprising repetitive enhancer of zeste motifs (EZH2)
were identified in the founding parents of a resource Atlantic salmon
population. We mapped the SCARB1-2 paralog to a region on Atlantic
salmon chromosome 1, containing a putative QTL for flesh colour.
Addition of the SCARB1-2 marker increased the significance of this
QTL, however the large confidence interval surrounding the QTL precludes
confirmation of SCARB1-2 as a causative gene underlying variation
in this trait.CONCLUSION:We have characterised a novel paralog of
SCARB1 (SCARB1-2), have mapped it to Atlantic salmon chromosome 1
and have described its expression in various tissues. Mapping with
SCARB1-2 alleles added further evidence for a QTL affecting flesh
colour on this chromosome, however further studies are needed to
confirm a functional role for this gene in flesh colour pigmentation.},
doi = {10.1186/1471-2156-12-52},
issn = {1471-2156},
pubmedid = {21619714},
url = {http://www.biomedcentral.com/1471-2156/12/52}
}
@ARTICLE{Sundvold2010,
author = {Sundvold, Hilde and Ruyter, Bente and Østbye, Tone-Kari and Moen,
Thomas},
title = {Identification of a novel allele of peroxisome proliferator-activated
receptor gamma (PPARG) and its association with resistance to Aeromonas
salmonicida in Atlantic salmon (Salmo salar)},
journal = {Fish \& Shellfish Immunology},
year = {2010},
volume = {28},
pages = {394--400},
number = {2},
month = feb,
abstract = {Bacterial and viral diseases are major problems in Atlantic salmon
aquaculture, but may be challenged through selection of brood stock
with enhanced survival to diseases. Today's selection strategy is
based on controlled challenge tests using siblings of the breeding
candidates, and is thus indirect. Direct trait records on breeding
candidates can potentially be provided through identification of
genetic variation linked to the susceptibility to the disease. Peroxisome
proliferator-activated receptor gamma (PPARG) is a lipid-sensing
transcription factor primarily known for inducing fat-accumulation
in adipocytes, but also in lipid-accumulating macrophages, in mammalian
species. Here we report a novel allele of PPARG, pparg-2, in Atlantic
salmon. pparg-2 has an insertion of sixty nucleotides that encodes
two additional copies of the almost perfect decapeptide motif, (F/C/Y)NHSPDR(S/N)HS,
compared to the previously described pparg-1. pparg-1 contains six
copies of this repeat unit whereas eight copies are present in the
novel pparg-2 allele. pparg-2 mRNA was detectable in kidney and spleen
of random Atlantic salmon samples. Here, we studied the effect of
pparg-1 and pparg-2 on survival upon challenge to a highly virulent
bacterium, Aeromonas salmonicida, causing furunculosis, and the virus
causing infectious salmon anaemia (ISA), respectively, in a Norwegian
aquaculture population of Atlantic salmon. ppar alleles were found
to be significantly associated with survival upon challenge to A.
salmonicida, but not to ISA. pparg-2 was the better allele in terms
of survival in the challenge test for furunculosis, survival rates
being 0.32, 0.40 and 0.42 for animals with the pparg-1,-1, pparg-1,
-2 and pparg-2, -2 genotypes, respectively. We conclude that pparg-2
is in linkage disequilibrium (LD) with, or identical to, a locus
contributing to different susceptibility to furunculosis in Atlantic
salmon. PPARG was mapped to linkage group eight (LG8) but could only
be positioned on the male linkage map since all the informative parents
in the mapping families were males. This is the first report showing
an association between pparg alleles and an enhanced immune response
in fish.},
issn = {1050-4648},
keywords = {Atlantic salmon, Disease resistance, Furunculosis, Peroxisome proliferator-activated
receptor gamma, Alleles, Challenge test, Genetic mapping},
url = {http://www.sciencedirect.com/science/article/B6WFN-4XWMNCD-3/2/fc4d1839e90a130e20af0af158cebccb}
}
@ARTICLE{Sung2007,
author = {Sung, Fion L. and Hui, Edwin P. and Tao, Qian and Li, Hongyu and
Tsui, Nancy B.Y. and Dennis Lo, Y.M. and Ma, Brigette B.Y. and To,
Ka F. and Harris, Adrian L. and Chan, Anthony T.C.},
title = {Genome-wide expression analysis using microarray identified complex
signaling pathways modulated by hypoxia in nasopharyngeal carcinoma},
journal = {Cancer Letters},
year = {2007},
volume = {253},
pages = {74--88},
number = {1},
month = aug,
abstract = {Previously, we showed that hypoxia-inducible factor (HIF)-1[alpha],
HIF-2[alpha], carbonic anhydrase IX (CA IX), and vascular endothelial
growth factor (VEGF) were frequently coexpressed in tumor biopsies
from patients of nasopharyngeal carcinoma (NPC) and were associated
with poor outcome after radiotherapy. Here, we further studied hypoxic
induction of HIF-1[alpha], HIF-2[alpha], CA IX, and VEGF in NPC cell
lines, investigated hypoxia-modulated gene expression in NPC cell
lines by Affymetrix GeneChip Array expression profiling, and identified
pathways influenced by hypoxia and novel genes not previously recognized
as hypoxia-inducible. Differentially regulated genes under hypoxia
were identified genome widely and selected genes validated by RT-PCR.
We found that hypoxia induced HIF-1[alpha], CA IX and VEGF expression
but not HIF-2[alpha] in NPC cells. Microarray expression analysis
showed that 222 genes were commonly up-regulated and 137 genes down-regulated
in hypoxic-treated CNE-2 and HONE-1 cells. Hypoxia induced broad
changes of both up- and down-regulated gene expressions involved
in diverse biological processes in NPC cells. Elucidation of the
coordinated functions modulated by hypoxia could lead to a better
understanding of the clinical significance of the hypoxic tumor phenotype.},
issn = {0304-3835},
keywords = {Hypoxia, Nasopharyngeal carcinoma, Microarray, Gene expression, Gene
ontology, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6T54-4N3X0XB-4/2/239b461106a7ccb1921c46a698a3a476}
}
@ARTICLE{Sung2009,
author = {Sung, Kai-Feng and Odinokova, Irina V. and Mareninova, Olga A. and
Rakonczay Jr, Zoltán and Hegyi, Péter and Pandol, Stephen J. and
Gukovsky, Ilya and Gukovskaya, Anna S.},
title = {Prosurvival Bcl-2 proteins stabilize pancreatic mitochondria and
protect against necrosis in experimental pancreatitis},
journal = {Experimental Cell Research},
year = {2009},
volume = {315},
pages = {1975--1989},
number = {11},
month = jul,
abstract = {Acinar cells in pancreatitis die through apoptosis and necrosis, the
roles of which are different. The severity of experimental pancreatitis
correlates directly with the extent of necrosis and inversely, with
apoptosis. Apoptosis is mediated by the release of cytochrome c into
the cytosol followed by caspase activation, whereas necrosis is associated
with the mitochondrial membrane potential ([Delta][Psi]m) loss leading
to ATP depletion. Here, we investigate the role of Bcl-2 proteins
in apoptosis and necrosis in pancreatitis. We found up-regulation
of prosurvival Bcl-2 proteins in pancreas in various experimental
models of acute pancreatitis, most pronounced for Bcl-xL. This up-regulation
translated into increased levels of Bcl-xL and Bcl-2 in pancreatic
mitochondria. Bcl-xL/Bcl-2 inhibitors induced [Delta][Psi]m loss
and cytochrome c release in isolated mitochondria. Corroborating
the results on mitochondria, Bcl-xL/Bcl-2 inhibitors induced [Delta][Psi]m
loss, ATP depletion and necrosis in pancreatic acinar cells, both
untreated and hyperstimulated with CCK-8 (in vitro pancreatitis model).
Together Bcl-xL/Bcl-2 inhibitors and CCK induced more necrosis than
either treatment alone. Bcl-xL/Bcl-2 inhibitors also stimulated cytochrome
c release in acinar cells leading to caspase-3 activation and apoptosis.
However, different from their effect on pronecrotic signals, the
stimulation by Bcl-xL/Bcl-2 inhibitors of apoptotic responses was
less in CCK-treated than control cells. Therefore, Bcl-xL/Bcl-2 inhibitors
potentiated CCK-induced necrosis but not apoptosis. Correspondingly,
transfection with Bcl-xL siRNA stimulated necrosis but not apoptosis
in the in vitro pancreatitis model. Further, in animal models of
pancreatitis Bcl-xL up-regulation inversely correlated with necrosis,
but not apoptosis. Results indicate that Bcl-xL and Bcl-2 protect
acinar cells from necrosis in pancreatitis by stabilizing mitochondria
against death signals. We conclude that Bcl-xL/Bcl-2 inhibition would
aggravate acute pancreatitis, whereas Bcl-xL/Bcl-2 up-regulation
presents a strategy to prevent or attenuate necrosis in pancreatitis.},
issn = {0014-4827},
keywords = {Pancreatic acinar cell, Bcl-xL, CCK, Mitochondrial membrane potential,
Cytochrome c release, Caspase-3},
url = {http://www.sciencedirect.com/science/article/B6WFC-4VFK80J-1/2/45a1862127fcb790fe10e65a4e645370}
}
@ARTICLE{Sung2003,
author = {Sung, Su Whan and Park, Sunwon and Yoon, Dae Sung and Lee, Youngsun
and Lim, Geunbae},
title = {Modeling and Control of a Microthermal Cycler for DNA Polymerase
Chain Reaction},
journal = {Industrial \& Engineering Chemistry Research},
year = {2003},
volume = {42},
pages = {6104-6111},
number = {24},
doi = {10.1021/ie030031d},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ie030031d},
url = {http://pubs.acs.org/doi/abs/10.1021/ie030031d}
}
@ARTICLE{Sung2006,
author = {Sung, Sun-Sang J. and Fu, Shu Man and Rose, C. Edward, Jr. and Gaskin,
Felicia and Ju, Shyr-Te and Beaty, Steven R.},
title = {A Major Lung CD103 ({alpha}E)-beta7 Integrin-Positive Epithelial
Dendritic Cell Population Expressing Langerin and Tight Junction
Proteins},
journal = {J. Immunol.},
year = {2006},
volume = {176},
pages = {2161--2172},
number = {4},
month = feb,
abstract = {Dendritic cells (DC) mediate airway Ag presentation and play key roles
in asthma and infections. Although DC subsets are known to perform
different functions, their occurrence in mouse lungs has not been
clearly defined. In this study, three major lung DC populations have
been found. Two of them are the myeloid and plasmacytoid DC (PDC)
well-characterized in other lymphoid organs. The third and largest
DC population is the integrin {alpha}E (CD103) [beta]7-positive and
I-AhighCD11chigh-DC population. This population was found to reside
in the lung mucosa and the vascular wall, express a wide variety
of adhesion and costimulation molecules, endocytose avidly, present
Ag efficiently, and produce IL-12. Integrin {alpha}E[beta]7+ DC ({alpha}E-DC)
were distinct from intraepithelial lymphocytes and distinguishable
from CD11bhigh myeloid and mPDCA-1+B220+Gr-1+ PDC populations in
surface marker phenotype, cellular functions, and tissue localization.
Importantly, this epithelial DC population expressed high levels
of the Langerhans cell marker Langerin and the tight junction proteins
Claudin-1, Claudin-7, and ZO-2. In mice with induced airway hyperresponsiveness
and eosinophilia, {alpha}E-DC numbers were increased in lungs, and
their costimulation and adhesion molecules were up-regulated. These
studies show that {alpha}E-DC is a major and distinct lung DC population
and a prime candidate APC with the requisite surface proteins for
migrating across the airway epithelia for Ag and pathogen capture,
transport, and presentation. They exhibit an activated phenotype
in allergen-induced lung inflammation and may play significant roles
in asthma pathogenesis.},
url = {http://www.jimmunol.org/cgi/content/abstract/176/4/2161}
}
@ARTICLE{Surace2004,
author = {Surace, Ezequiel I. and Lusis, Eriks and Haipek, Carrie A. and Gutmann,
David H.},
title = {Functional significance of S6K overexpression in meningioma progression},
journal = {Ann Neurol.},
year = {2004},
volume = {56},
pages = {295--298},
number = {2},
abstract = {Abstract 10.1002/ana.20201.abs One common genetic change in anaplastic
meningiomas is amplification of chromosome 17q23 containing the S6
kinase (S6K) gene. We show, for the first time to our knowledge,
increased S6K mRNA expression in anaplastic meningiomas compared
with benign tumors. To evaluate S6K as a candidate meningioma progression
gene, we generated IOMM-Lee human meningioma cell lines overexpressing
S6K. Whereas no effect of S6K overexpression on meningioma cell growth,
motility, or adhesion was observed in vitro, S6K overexpression resulted
in increased tumor size in vivo. Collectively, these results suggest
that S6K is functionally important for meningioma progression and
may represent a target for future meningioma therapy. Ann Neurol
2004},
issn = {1531-8249},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ana.20201}
}
@ARTICLE{Surgucheva2008,
author = {Surgucheva, Irina and Shestopalov, Valery I. and Surguchov, Andrei},
title = {Effect of {gamma}-Synuclein Silencing on Apoptotic Pathways in Retinal
Ganglion Cells},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {36377--36385},
number = {52},
month = dec,
abstract = {{gamma} -Synuclein (Syn G) is highly expressed in retinal ganglion
cells and the loss of these cells in glaucoma is associated with
significant reduction of the intracellular Syn G level. However,
a causative relationship between these two events has not been established.
Here we show that the knockdown of Syn G results in a decreased viability
of the immortalized retinal ganglion cells (RGC-5). The Syn G silencing
reduces phosphorylation of serine 112 (Ser112) in Bad protein, a
member of the Bcl-2 family that plays a critical role in apoptotic
cell death signaling. Our gene expression analysis data suggests
that changes in Bad phosphorylation status may be caused by a coordinated
shift in activities of kinases controlling Bad phosphorylation and
phosphatases catalyzing its dephosphorylation. Moreover, increased
phosphorylation of Bad-sequestering protein 14-3-3 detected in these
cells is also pro-apoptotic. These results suggest that the homeostatic
level of Syn G in RGC-5 cells is required for transcriptional regulation
of protein kinases and phosphatases, controlling phosphorylation
of Bad and 14-3-3. Lowering Syn G causes Bad dephosphorylation, dissociation
from phosphorylated 14-3-3, and translocation to mitochondria where
it initiates apoptotic death cascade.},
url = {http://www.jbc.org/cgi/content/abstract/283/52/36377}
}
@ARTICLE{Surridge2011,
author = {Surridge, Alison and Lopez-Gomollon, Sara and Moxon, Simon and Maroja,
Luana and Rathjen, Tina and Nadeau, Nicola and Dalmay, Tamas and
Jiggins, Chris},
title = {Characterisation and expression of microRNAs in developing wings
of the neotropical butterfly Heliconius melpomene },
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {62},
number = {1},
abstract = {BACKGROUND:Heliconius butterflies are an excellent system for studies
of adaptive convergent and divergent phenotypic traits. Wing colour
patterns are used as signals to both predators and potential mates
and are inherited in a Mendelian manner. The underlying genetic mechanisms
of pattern formation have been studied for many years and shed light
on broad issues, such as the repeatability of evolution. In Heliconius
melpomene, the yellow hindwing bar is controlled by the HmYb locus.
MicroRNAs (miRNAs) are important post-transcriptional regulators
of gene expression that have key roles in many biological processes,
including development. miRNAs could act as regulators of genes involved
in wing development, patterning and pigmentation. For this reason
we characterised miRNAs in developing butterfly wings and examined
differences in their expression between colour pattern races.RESULTS:We
sequenced small RNA libraries from two colour pattern races and detected
142 Heliconius miRNAs with homology to others found in miRBase. Several
highly abundant miRNAs were differentially represented in the libraries
between colour pattern races. These candidates were tested further
using Northern blots, showing that differences in expression were
primarily due to developmental stage rather than colour pattern.
Assembly of sequenced reads to the HmYb region identified hme-miR-193
and hme-miR-2788; located 2380 bp apart in an intergenic region.
These two miRNAs are expressed in wings and show an upregulation
between 24 and 72 hours post-pupation, indicating a potential role
in butterfly wing development. A search for miRNAs in all available
H. melpomene BAC sequences (~ 2.5 Mb) did not reveal any other miRNAs
and no novel miRNAs were predicted.CONCLUSIONS:Here we describe the
first butterfly miRNAs and characterise their expression in developing
wings. Some show differences in expression across developing pupal
stages and may have important functions in butterfly wing development.
Two miRNAs were located in the HmYb region and were expressed in
developing pupal wings. Future work will examine the expression of
these miRNAs in different colour pattern races and identify miRNA
targets among wing patterning genes.},
doi = {10.1186/1471-2164-12-62},
issn = {1471-2164},
pubmedid = {21266089},
url = {http://www.biomedcentral.com/1471-2164/12/62}
}
@ARTICLE{Suslov2005,
author = {Suslov, Oleg and Steindler, Dennis A.},
title = {PCR inhibition by reverse transcriptase leads to an overestimation
of amplification efficiency},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {e181--},
number = {20},
month = nov,
abstract = {This study addresses the problem of PCR inhibition by reverse transcriptase.
It has been shown that the inhibition occurs mostly when a small
amount of RNA is taken for RT reaction, and it is more visible for
rarely expressed transcripts. We show here that the inhibition takes
place regardless of what amount of template is utilized for RT. The
inhibition possesses a global nature, i.e. the amplification of any
given transcript may be compromised with different levels of inhibition.
The process of inhibition also explains wrongfully derived PCR amplification
efficiencies, sometimes more than 100%, when the sequential dilutions
of unpurified RT sample are utilized to build the calibration curve.
The RT influences PCR not only by inhibiting it. When microgram(s)
of RNA are taken for RT reaction, reverse transcriptase may cause
overamplification of some transcripts under certain PCR conditions.
The possible mechanism of RT influence on PCR is presented, and a
purification method is implemented to remove the effects of RT on
PCR.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/20/e181}
}
@ARTICLE{Sussarellu2010,
author = {Sussarellu, Rossana and Fabioux, Caroline and Le Moullac, Gilles
and Fleury, Elodie and Moraga, Dario},
title = {Transcriptomic response of the Pacific oyster Crassostrea gigas to
hypoxia},
journal = {Marine Genomics},
year = {2010},
volume = {3},
pages = {133--143},
number = {3-4},
month = sep,
abstract = {Marine intertidal organisms commonly face hypoxic stress during low
tide emersion; moreover, eutrophic conditions and sediment nearness
could lead to hypoxic phenomena; it is indeed important to understand
the molecular processes involved in the response to hypoxia. In this
study the molecular response of the Pacific oyster Crassostrea gigas
to prolonged hypoxia (2 mg O2 L- 1 for 20 d) was investigated under
experimental conditions. A transcriptomic approach was employed using
a cDNA microarray of 9058 C. gigas clones to highlight the genetic
expression patterns of the Pacific oyster under hypoxic conditions.
Lines of oysters resistant (R) and susceptible (S) to summer mortality
were used in this study. ANOVA analysis was used to identify the
genes involved in the response to hypoxia in comparison to normoxic
conditions. The hypoxic response was maximal at day 20. The principal
biological processes up-regulated by hypoxic stress were antioxidant
defense and the respiratory chain compartment, suggesting oxidative
stress caused by hypoxia or an anticipatory response for normoxic
recovery. This is the first study employing microarrays to characterize
the genetic markers and metabolic pathways responding to hypoxic
stress in C. gigas.},
issn = {1874-7787},
keywords = {Mollusca, Hypoxia, cDNA microarray, Gene expression, Oxidative stress,
Respiratory chain},
url = {http://www.sciencedirect.com/science/article/pii/S1874778710000292}
}
@ARTICLE{Sussarellu2012,
author = {Rossana Sussarellu and Caroline Fabioux and Miguel Camacho Sanchez
and Nelly Le Goïc and Christophe Lambert and Philippe Soudant and
Dario Moraga},
title = {Molecular and cellular response to short-term oxygen variations in
the Pacific oyster Crassostrea gigas},
journal = {Journal of Experimental Marine Biology and Ecology},
year = {2012},
volume = {412},
pages = {87 - 95},
number = {0},
abstract = {Intertidal organisms have to face daily high oxygen variations from
hypoxic to hyperoxic conditions. To cope with such constraints, these
organisms must have well developed compensatory mechanisms involving
antioxidant and energetic adjustments. The oyster Crassostrea gigas
is regularly exposed to high oxygen fluctuations and is a good model
to understand these physiological regulations. This study aimed to
explore the mechanisms involved in response to short-term oxygen
variations in the digestive gland and hemocytes of C. gigas. The
effects of returning into water after an emersion period were tested
for 24 h at two different oxygen concentrations (normoxic 8.8 mg O2 L−1
and hypoxic 2.6 mg O2 L−1). Gene expression on several
antioxidant enzymes was performed. In addition, a marker of oxidative
damage, the malondialdehyde (MDA) was quantified. Hemocyte parameters
measured were viability, concentration of different cellular sub-populations
and oxidative activity. Changes in energetic metabolism were investigated
measuring mRNA levels of pyruvate kinase (PK) and phosphoenolpyruvate
carboxykinase (PEPCK). Moreover, mRNA levels of the transcription
factor HIFα were analyzed. Higher levels of the alternative oxidase
(AOX) mRNA in normoxic conditions corroborate the hypothesis of the
AOX having a role in the redox balance. MDA levels did not show any
condition effect, suggesting that hypoxic conditions did not cause
oxidative stress. mRNA levels of antioxidant enzymes and hemocyte
oxidative activity increased during the 24 h of immersion. This
suggests that the disruption of tidal cycles by maintaining oysters
immersed resulted in an increase of oxygen-dependent activities.
No clear hypoxic responses were detected neither in a switch of PEPCK
and PK toward anaerobic metabolism, nor in HIFα regulation. PK mRNA
levels were significantly higher in nomoxic conditions, suggesting
that more elevated oxygen concentrations would lead to higher energetic
metabolism. Hemocyte concentrations were higher in hypoxic conditions
suggesting an increased hematopoiesis. This study brings new insights
in understanding how oysters, and more in general intertidal molluscs,
cope with short-term oxygen variations.},
doi = {10.1016/j.jembe.2011.11.007},
issn = {0022-0981},
keywords = {Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0022098111005065}
}
@ARTICLE{Susuki2011,
author = {Susuki, Dai and Kimura, Sotai and Naganuma, Seiji and Tsuchiyama,
Katsuki and Tanaka, Toshiaki and Kitamura, Naomi and Fujieda, Shigeharu
and Itoh, Hiroshi},
title = {Regulation of microRNA expression by hepatocyte growth factor in
human head and neck squamous cell carcinoma},
journal = {Cancer Science},
year = {2011},
volume = {102},
pages = {2164--2171},
number = {12},
abstract = {Hepatocyte growth factor (HGF) is a multifunctional molecule that
acts as mitogen, motogen, and/or morphogen in a variety of cells.
MET, a specific receptor tyrosine kinase for HGF, is upregulated
in various tumors including squamous cell carcinoma of the human
head and neck (HNSCC), but how HGF affects the expression of downstream
functional genes has not yet been elucidated in detail. In the present
study, we examined the expression of microRNA (miRNA), non-coding
small RNA that regulate cell proliferation and functions by interfering
with the translation of target mRNA, with or without HGF stimulation
in HNSCC cell line HSC3. Among several miRNAs, in which the expression
was altered after HGF stimulation, we focused on miR-200c and miR-27b,
both of which were drastically downregulated after HGF stimulation.
Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3
and 6Â h after HGF stimulation, and that of E-cadherin, a downstream
molecule of ZEB1, was downregulated 12Â h after HGF stimulation.
Expression of ST14/matriptase, an enzyme for extracellular matrix
(ECM) degradation and HGF activation and a target mRNA for miR-27b,
was drastically upregulated in the protein level after HGF stimulation,
although it was not statistically altered in the mRNA level. These
results suggest that miR-200c and miR-27b downregulated by HGF might
play an important role in epithelial–mesenchymal transition mediated
by ZEB1/E-cadherin and ECM degradation and HGF autoactivation mediated
by ST14/matriptase, respectively. Altered expression of miRNA directly
regulated by HGF might contribute enhanced progressive and invasive
characteristics of HNSCC by regulating the translation of HGF-induced
functional molecules. (Cancer Sci 2011; 102: 2164–2171)},
doi = {10.1111/j.1349-7006.2011.02096.x},
issn = {1349-7006},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1349-7006.2011.02096.x}
}
@ARTICLE{Sutherland2011,
author = {Sutherland, Allison and Thomas, Mervyn and Brandon, Roslyn and Brandon,
Richard and Lipman, Jeffrey and Tang, Benjamin and McLean, Anthony
and Pascoe, Ranald and Price, Gareth and Nguyen, Thu and Stone, Glenn
and Venter, Deon},
title = {Development and validation of a novel molecular biomarker diagnostic
test for the early detection of sepsis},
journal = {Critical Care},
year = {2011},
volume = {15},
pages = {R149},
number = {3},
abstract = {INTRODUCTION:Sepsis is a complex immunological response to infection
characterized by early hyper-inflammation followed by severe and
protracted immunosuppression, suggesting that a multi-marker approach
has the greatest clinical utility for early detection, within a clinical
environment focused on Systemic Inflammatory Response Syndrome (SIRS)
differentiation. Pre-clinical research using an equine sepsis model
identified a panel of gene expression biomarkers that define the
early aberrant immune activation. Thus, the primary objective was
to apply these gene expression biomarkers to distinguish patients
with sepsis from those who had undergone major open surgery and had
clinical outcomes consistent with systemic inflammation due to physical
trauma and wound healing.METHODS:This was a multi-centre, prospective
clinical trial conducted across four tertiary critical care settings
in Australia. Sepsis patients were recruited if they met the 1992
Consensus Statement criteria and had clinical evidence of systemic
infection based on microbiology diagnoses (n = 27). Participants
in the post-surgical (PS) group were recruited pre-operatively and
blood samples collected within 24 hours following surgery (n = 38).
Healthy controls (HC) included hospital staff with no known concurrent
illnesses (n = 20). Each participant had minimally 5 ml of PAXgene
blood collected for leucocyte RNA isolation and gene expression analyses.
Affymetrix array and multiplex tandem (MT)-PCR studies were conducted
to evaluate transcriptional profiles in circulating white blood cells
applying a set of 42 molecular markers that had been identified a
priori. A LogitBoost algorithm was used to create a machine learning
diagnostic rule to predict sepsis outcomes.RESULTS:Based on preliminary
microarray analyses comparing HC and sepsis groups, a panel of 42-gene
expression markers were identified that represented key innate and
adaptive immune function, cell cycling, WBC differentiation, extracellular
remodelling and immune modulation pathways. Comparisons against GEO
data confirmed the definitive separation of the sepsis cohort. Quantitative
PCR results suggest the capacity for this test to differentiate severe
systemic inflammation from HC is 92%. The area under the curve (AUC)
receiver operator characteristics (ROC) curve findings demonstrated
sepsis prediction within a mixed inflammatory population, was between
86 and 92%.CONCLUSIONS:This novel molecular biomarker test has a
clinically relevant sensitivity and specificity profile, and has
the capacity for early detection of sepsis via the monitoring of
critical care patients.},
doi = {10.1186/cc10274},
issn = {1364-8535},
pubmedid = {21682927},
url = {http://ccforum.com/content/15/3/R149}
}
@ARTICLE{Sutherland2010,
author = {Sutherland, Katherine M. and Combs, Trenton J. and Edwards, Patricia
C. and Laura, S. Van Winkle},
title = {Site-specific Differences in Gene Expression of Secreted Proteins
in the Mouse Lung: Comparison of Methods to Show Differences by Location},
journal = {Journal of Histochemistry \& Cytochemistry},
year = {2010},
volume = {58},
pages = {1107--1119},
number = {12},
month = dec,
abstract = {Studies on the effects of pulmonary toxicants on the lung often overlook
the fact that site-specific changes are likely to occur in response
to chemical exposure. These changes can be highly focal and may be
undetected by methods that do not examine specific lung regions.
This problem is especially acute for studies of the conducting airways.
In this study, differential gene expression of secreted proteins
in the lung by different methods of collection (whole lung, gross
airway microdissection, and laser capture microdissection) and by
airway levels (whole lobe, whole airway tree, proximal airways, airway
bifurcations, and terminal bronchioles) was examined. Site-specific
sampling approaches were combined with methods to detect both gene
and corresponding protein expression in different lung regions. Differential
expression of mRNA by both airway level and lung region was determined
for Clara cell secretory protein, calcitonin gene-related peptide,
uteroglobin-related protein 2, surfactant protein A, and surfactant
protein C. Therefore, for maximal enrichment of mRNA and maximal
ability to identify changes in mRNA levels in the diseased state
or in response to chemical exposure, it is critical to choose the
appropriate airway region and sample collection method to enrich
detection of the transcript(s) of interest. (J Histochem Cytochem
58:1107-1119, 2010)},
comment = {10.1369/jhc.2010.956052},
url = {http://jhc.sagepub.com/cgi/content/abstract/58/12/1107}
}
@ARTICLE{Sutton2008,
author = {Sutton, Thomas L. and Zhao, Aiping and Madden, Kathleen B. and Elfrey,
Justin E. and Tuft, Blaine A. and Sullivan, Carolyn A. and Urban,
Joseph F., Jr. and Shea-Donohue, Terez},
title = {Anti-Inflammatory Mechanisms of Enteric Heligmosomoides polygyrus
Infection against Trinitrobenzene Sulfonic Acid-Induced Colitis in
a Murine Model},
journal = {Infect. Immun.},
year = {2008},
volume = {76},
pages = {4772--4782},
number = {10},
month = oct,
abstract = {Recent studies showed that enteric helminth infection improved symptoms
in patients with inflammatory bowel disease as well as in experimental
models of colitis. The aim of this study was to determine the mechanism
of the protective effect of helminth infection on colitis-induced
changes in immune and epithelial cell function. BALB/c mice received
an oral infection of Heligmosomoides polygyrus third-stage larvae,
were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS)
on day 10 postinfection, and were studied 4 days later. Separate
groups of mice received intrarectal saline or TNBS on day 10 and
were studied on day 14. Muscle-free colonic mucosae were mounted
in Ussing chambers to measure mucosal permeability and secretion.
Expression of cytokines was assessed by quantitative real-time PCR,
and mast cells were visualized by immunohistochemistry. TNBS-induced
colitis induced mucosal damage, upregulated Th1 cytokines, and depressed
secretory responses. Heligmosomoides polygyrus elevated Th2 cytokine
expression, increased mast cell infiltration and mucosal resistance,
and also reduced some secretory responses. Prior H. polygyrus infection
prevented TNBS-induced upregulation of Th1 cytokines and normalized
secretory responses to specific agonists. TNBS-induced colitis did
not alter H. polygyrus-induced mast cell infiltration or upregulation
of Th2 cytokine expression. The results indicate that the protective
mechanism of enteric nematode infection against TNBS-induced colitis
involves prevention of Th1 cytokine expression and improved colonic
function by a mechanism that may involve mast cell-mediated protection
of neural control of secretory function. Similar response patterns
could account for the clinical improvement seen in inflammatory bowel
disease with helminthic therapy.},
url = {http://iai.asm.org/cgi/content/abstract/76/10/4772}
}
@ARTICLE{Suvorov2011,
author = {Suvorov, Alexander and Bissonnette, Cyntia and Takser, Larissa and
Langlois, Marie-France},
title = {Does 2,2',4,4'-tetrabromodiphenyl ether interact directly with thyroid
receptor?},
journal = {Journal of Applied Toxicology},
year = {2011},
volume = {31},
pages = {179--184},
number = {2},
abstract = {Abstract 2,2′,4,4′-tetrabromodiphenyl Ether (BDE-47) is a flame-retardant
chemical appearing at increasing concentrations and frequency in
the environment and human samples. A number of health effects of
exposure to BDE-47 have been observed, thyroid disruption being the
most sensitive. Our objective was to examine BDE-47 interaction with
thyroid receptor beta (TRβ). We used a variety of approaches, including
in vitro binding assays, luciferase reporter-gene transcriptional
assays, and analysis of expression of thyroid responsive genes in
rat offspring exposed perinatally to BDE-47. We found that BDE-47
alone or in mixture with 2,2′,4,4′,5-pentabromodiphenyl ether
(BDE-99), 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100), and
2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE-153) does not compete
with [125I]T3 for TRβ-binding even at 4000 fold higher concentrations.
Also, BDE-47 does not affect thyroid responsive genes through TRβ
in in vitro studies of transcription regulation. A subset of thyroid
responsive genes were significantly differentially expressed in liver
and frontal lobe brain samples of exposed pups, however, the action
of BDE-47 was neither agonistic or antagonistic to that of thyroid
hormone. We conclude that BDE-47 does not interact directly with
TRβ1 nor does it influence its transcriptional activity. Developmental
exposure of rats to BDE-47 leads to differential expression of thyroid
responsive genes in liver and brain due to unknown mechanism. Copyright
© 2010 John Wiley & Sons, Ltd.},
doi = {10.1002/jat.1580},
issn = {1099-1263},
keywords = {PBDE, thyroid hormone receptor, environmental toxicology, thyroid
hormone response element, gene expression, microarrays},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/jat.1580}
}
@ARTICLE{Suvorov2011a,
author = {Suvorov, Alexander and Takser, Larissa},
title = {Delayed response in the rat frontal lobe transcriptome to perinatal
exposure to the flame retardant BDE-47},
journal = {Journal of Applied Toxicology},
year = {2011},
volume = {31},
pages = {477--483},
number = {5},
abstract = {BDE-47 is the most prevalent congener of polybrominated diphenyl ethers,
which are widely used flame retardants, and is known for endocrine
and behavioral disrupting properties in animals. Transient effect
on spontaneous motor activity in rats following perinatal exposure
to BDE-47 at low doses, relevant to human exposure, was reported
in our previous study. The objective of this study was to screen
for the long-term effects on gene expression in the brain of rats
perinatally exposed to BDE-47. Wistar dams were exposed to BDE-47
(0.002 and 0.2 mg kg−1 body weight) from gestation day 15 to
postnatal day (PND) 20. Total RNA was extracted from the whole brain
at PND10 and the brain frontal lobes at PND41 and hybridized to whole-genome
RNA expression microarrays. The genes, differentially expressed 1.5-fold,
were analyzed with the DAVID bioinformatics resources for cluster
and gene-term enrichment. At PND41, clusters of genes involved in
nerve impulse transmission, nervous system development and functioning,
and core biosynthetic process were altered, including several downregulated
genes of cation channels. Representation of LINE1 RNA was decreased
significantly. Altered expression of genes involved in neurodevelopment
occured at least 3 weeks after the last exposure and the behavioral
manifestation of low dose BDE-47 toxicity. Copyright © 2011 John
Wiley & Sons, Ltd.},
doi = {10.1002/jat.1667},
issn = {1099-1263},
keywords = {genomics, neurodevelopment, microarray, gene expression, rat, PBDE},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/jat.1667}
}
@ARTICLE{Suwanwela2011,
author = {Suwanwela, Jaijam and Farber, Charles R and Haung, Bau-lin and Song,
Buer and Pan, Calvin and Lyons, Karen M and Lusis, Aldons J},
title = {Systems genetics analysis of mouse chondrocyte differentiation},
journal = {Journal of Bone and Mineral Research},
year = {2011},
volume = {26},
pages = {747--760},
number = {4},
abstract = {Abstract One of the goals of systems genetics is the reconstruction
of gene networks that underlie key processes in development and disease.
To identify cartilage gene networks that play an important role in
bone development, we used a systems genetics approach that integrated
microarray gene expression profiles from cartilage and bone phenotypic
data from two sets of recombinant inbred strains. Microarray profiles
generated from isolated chondrocytes were used to generate weighted
gene coexpression networks. This analysis resulted in the identification
of subnetworks (modules) of coexpressed genes that then were examined
for relationships with bone geometry and density. One module exhibited
significant correlation with femur length (r = 0.416), anteroposterior
diameter (r = 0.418), mediolateral diameter (r = 0.576),
and bone mineral density (r = 0.475). Highly connected genes
(n = 28) from this and other modules were tested in vitro using
prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes
were found to play a role in chondrocyte differentiation. Two of
these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte
development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3,
are novel genes. Our integrative analysis provided a systems-level
view of cartilage development and identified genes that may be involved
in bone development. © 2011 American Society for Bone and Mineral
Research.},
doi = {10.1002/jbmr.271},
issn = {1523-4681},
keywords = {CARTILAGE DEVELOPMENT, SYSTEMS GENETICS, COEXPRESSION NETWORK, MODULE,
QUANTITATIVE TRAIT LOCUS, GENE KNOCKDOWN},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jbmr.271}
}
@ARTICLE{Suyama2010,
author = {Suyama, Takahito and Shiraishi, Takumi and Zeng, Yu and Yu, Wayne
and Parekh, Nehal and Vessella, Robert L. and Luo, Jun and Getzenberg,
Robert H. and Kulkarni, Prakash},
title = {Expression of cancer/testis antigens in prostate cancer is associated
with disease progression},
journal = {Prostate},
year = {2010},
volume = {70},
pages = {1778--1787},
number = {16},
abstract = {Abstract BACKGROUND The cancer/testis antigens (CTAs) are a unique
group of proteins normally expressed in germ cells but aberrantly
expressed in several types of cancers including prostate cancer (PCa).
However, their role in PCa has not been fully explored. METHODS CTA
expression profiling in PCa samples and cell lines was done utilizing
a custom microarray that contained probes for two-thirds of all CTAs.
The data were validated by quantitative PCR (Q-PCR). Functional studies
were carried out by silencing gene expression with siRNA. DNA methylation
was determined by methylation-specific PCR. RESULTS A majority of
CTAs expressed in PCa are located on the X chromosome (CT-X antigens).
Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately
upregulated in castrate-resistant prostate cancer (CRPC) but not
in primary PCa. In contrast, PAGE4 is highly upregulated in primary
PCa but is virtually silent in CRPC. Further, there was good correlation
between the extent of promoter DNA methylation and CTA expression.
Finally, silencing the expression of MAGEA2 the most highly upregulated
member, significantly impaired proliferation of prostate cancer cells
while increasing their chemosensitivity. CONCLUSIONS Considered together,
the remarkable stage-specific expression patterns of the CT-X antigens
strongly suggests that these CTAs may serve as unique biomarkers
that could potentially be used to distinguish men with aggressive
disease who need treatment from men with indolent disease not requiring
immediate intervention. The data also suggest that the CT-X antigens
may be novel therapeutic targets for CRPC for which there are currently
no effective therapeutics. Prostate 70: 1778–1787, 2010. © 2010
Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {cancer/testis antigens, prostate cancer, castrate-resistant prostate
cancer, biomarker},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.21214}
}
@ARTICLE{Suzuki2007,
author = {Suzuki, Atsuko and Urushitani, Hiroshi and Sato, Tomomi and Kobayashi,
Tomohiro and Watanabe, Hajime and Ohta, Yasuhiko and Iguchi, Taisen},
title = {Gene Expression Change in the Mullerian Duct of the Mouse Fetus Exposed
to Diethylstilbestrol In Utero},
journal = {Exp Biol Med},
year = {2007},
volume = {232},
pages = {503--514},
number = {4},
month = apr,
abstract = {In utero exposure to diethylstilbestrol (DES) induces various abnormalities
in the Mullerian duct of the mouse. In order to understand the underlying
molecular mechanisms associated with DES-induced abnormalities of
the Mullerian duct, gene expression was examined on Gestation Day
(GD) 19 in mouse fetuses exposed to DES (67 {micro}g/kg body weight)
from GDs 10 to 18. Microarray analysis revealed that 387, 387, and
225 genes were upregulated and 177, 172, and 75 genes were downregulated
by DES in the oviduct, uterus, and vagina, respectively. DES exposure
in utero commonly upregulated 72 genes and downregulated 15 genes
in these three organs. The present study demonstrated that organ-specific
gene expression patterns in the mouse Mullerian duct were altered
by in utero DES exposure. DES-induced changes in expression of genes
such as Dkk2, Nkd2, and sFRP1 as well as changes in genes of the
Hox, Wnt, and Eph families in the female mouse fetal reproductive
tract could be the basis for various abnormalities in reproductive
tracts following exposure to this estrogenic drug.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/232/4/503}
}
@ARTICLE{Suzuki2006,
author = {Suzuki, Atsuko and Watanabe, Hajime and Mizutani, Takeshi and Sato,
Tomomi and Ohta, Yasuhiko and Iguchi, Taisen},
title = {Global Gene Expression in Mouse Vaginae Exposed to Diethylstilbestrol
at Different Ages},
journal = {Exp Biol Med},
year = {2006},
volume = {231},
pages = {632--640},
number = {5},
month = may,
abstract = {Estrogens regulate proliferation and differentiation of cells in target
organs such as the female reproductive tract. In mature mice, estrogens
stimulate cell proliferation, whereas ovariectomy results in atrophy
of the female reproductive tract. In contrast, perinatal exposure
to estrogens, including diethylstilbestrol (DES), induces persistent,
ovary-independent vaginal stratification and cervico-vaginal tumors
later in life. These effects are due to altered cell fate following
DES exposure during a critical developmental period. The detailed
mechanisms underlying the reversible and irreversible cell proliferation
in vaginae induced by DES at different ages has not been clarified.
Therefore, we examined differences in gene expression pattern using
DNA microarray analysis in mouse vaginae 6 hrs after a single injection
of 2 {micro}g DES per gram of body weight, and proliferation of vaginal
epithelial and stromal cells 24 hrs after the injection at postnatal
days (PNDs) 0, 5, 20, and 70. After DES stimulation, vaginal epithelial
and stromal cells showed cell proliferation at PNDs 20 and 70, and
at PNDs 0 and 5, respectively. DNA microarray analysis exhibited
54 DES-induced genes and 9 DES-repressed genes in vaginae at PND
0, whereas more than 200 DES-induced genes were found in vaginae
at PNDs 5 and 20, and 350 genes at PND 70. Clustering analysis of
DES-induced genes in the vaginae at different ages revealed that
genes induced by DES at PND 5 were closer to the adult type than
that of PND 0. Genes related to keratinocyte differentiation, such
as Gadd45{alpha}, p21, 14-3-3 sigma, small proline-rich protein 2f
(Sprr2f), and Krupple-like factor 4 (Klf4), were induced by DES.
The number of DES-induced genes during the critical period, PND 0,
was smaller than those found after the critical period. These results
give insight toward understanding the molecular mechanisms underlying
the critical period in mouse vaginae.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/231/5/632}
}
@ARTICLE{Suzuki2010,
author = {Suzuki, Masahiro And Sugimoto, Kazushi And Tanaka, Junichiro And
Tameda, Masahiko And Inagaki, Yuji And Kusagawa, Satoko And Nojiri,
Keiichiro And Beppu, Tetsuya And Yoneda, Kentaro And Yamamoto, Norihiko
And Ito, Masaaki And Yoneda, Misao And Uchida, Kazuhiko And Takase,
Koujiro And Shiraki, Katsuya},
title = {Up-regulation of Glypican-3 in Human Hepatocellular Carcinoma},
journal = {Anticancer Res},
year = {2010},
volume = {30},
pages = {5055--5061},
number = {12},
month = dec,
abstract = {Aim: To investigate the expression and significance of glypican-3
(GPC3) in human hepatocellular carcinoma (HCC). Materials and Methods:
DNA chips were used to measure the expression of mRNAs for members
of the glypican and syndecan families of heparan sulfate proteoglycans
(HSPGs) in normal liver tissue, non-tumor tissues and HCC. GPC3 protein
expression was investigated by immunohistochemical staining in the
tissues samples and Western blotting in human HCC cell lines. In
addition, the levels of GPC3 protein in the blood were determined
by ELISA. Results: Only the expression of GPC3 was found to be markedly
elevated in HCCs. In the human HCC cell lines, GPC3 expression was
consistently observed, and was mainly located in the cell membrane
and cytoplasm. Immunohistochemistry showed a tendency for overall
staining of the cytoplasm of cells in the liver carcinoma tissues,
but the cell membrane was preferentially stained in poorly differentiated
HCC when compared with well-differentiated HCC. Moreover, the cell
membrane was preferentially stained in metastatic lesions of HCC
when compared with primary HCC lesions. Non-tumor tissues and cholangiocellular
carcinoma tissues were not stained. In addition, using HepG2 cells,
AG490 and piceatannol, which are signal transducer and activator
of transcription 3 (STAT3) inhibitors, each increased the amount
of GPC3 mRNA expressed. Assay of the circulating levels of GPC3 protein
in chronic liver disease and HCC found that serum GPC3 protein levels
were significantly elevated in the latter. Conclusion: GPC3 is highly
expressed in HCC, and its expression pattern differs according to
the degree of cell differentiation. In addition, the expression of
GPC3 is regulated by Janus kinase-STAT signaling. GPC3 shows potential
as a tumor biomarker for HCC that can be used for molecularly targeted
therapy.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/30/12/5055}
}
@ARTICLE{Suzuki2011,
author = {Suzuki, Masaru and Zeskind, Julie E. and McDonough, John E. and Gosselink,
John V. and Elliott, W M. and Hayashi, Shizu and Cooper, Joel D.
and Lenburg, Marc E. and Spira, Avrum and Hogg, James C.},
title = {Macrophage Polarization During Centrilobular Emphysematous Destruction
In COPD},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2011},
volume = {183},
pages = {A3004--},
number = {1_MeetingAbstracts},
month = may,
url = {http://ajrccm.atsjournals.org}
}
@ARTICLE{Suzuki2012,
author = {Naoki Suzuki and Tetsuya Akiyama and Toshiaki Takahashi and Hazuki
Komuro and Hitoshi Warita and Maki Tateyama and Yasuto Itoyama and
Masashi Aoki},
title = {Continuous administration of poloxamer 188 reduces overload-induced
muscular atrophy in dysferlin-deficient SJL mice},
journal = {Neuroscience Research},
year = {2012},
volume = {72},
pages = {181 - 186},
number = {2},
abstract = {Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy.
We demonstrated that poloxamer 188 (P188), a membrane sealant, is
effective in reducing the loss of muscle mass in SJL mice when administered
using an osmotic pump for 6 weeks. We did not observe significant
changes over a 2-week administration period, suggesting that longthier
observation is necessary to determine the effectiveness of P188.
We also examined exercise endurance in P188-administered SJL mice
using a rolling cage. Phosphorylated p38 was found to be reduced
in P188-administered SJL mice; additionally, using microarray analysis,
we found diminished expression of atrogin-1, an E3 ubiquitin ligase,
as the effector of muscular atrophy. Chronic infusion of P188 to
dysferlin-deficient SJL mice reduced muscular atrophy, and administering
p38 and atrogin-1 in the gastrocnemius muscle improved its motor
function. These results provide a basis for potential treatments
for dysferlin-deficient skeletal muscle fibers.},
doi = {10.1016/j.neures.2011.10.005},
issn = {0168-0102},
keywords = {Dysferlinopathy},
url = {http://www.sciencedirect.com/science/article/pii/S0168010211021109}
}
@ARTICLE{Suzuki2004,
author = {Suzuki, Shugo and Asamoto, Makoto and Tsujimura, Kazunari and Shirai,
Tomoyuki},
title = {Specific differences in gene expression profile revealed by cDNA
microarray analysis of glutathione S-transferase placental form (GST-P)
immunohistochemically positive rat liver foci and surrounding tissue},
journal = {Carcinogenesis},
year = {2004},
volume = {25},
pages = {439--443},
number = {3},
month = mar,
abstract = {Glutathione S-transferase placental form (GST-P), one of the glutathione
S-transferases family of detoxification enzymes, is a very useful
marker of rat liver pre-neoplastic lesions. We here investigated
the gene expression profile in GST-P positive foci as compared with
surrounding GST-P negative areas in the same liver of rats treated
with diethylnitrosamine and then 2-acetylaminofluorene combined with
partical hepatectomy. GST-P positive foci were harvested by laser
microdissection and total RNAs were extracted to allow gene expression
profiles to be assessed by cDNA microarray assays. Transaldolase,
rat aflatoxin B1 aldehyde reductase and gamma-glutamylcysteine synthetase
were found as up-regulated genes and regucalcin as a down-regulated
gene, in line with findings for hepatocellular carcinomas. The results
indicate that the approach adopted is useful for understanding mechanisms
of hepatocarcinogenesis and identification of new markers for rat
liver pre-neoplastic foci.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/25/3/439}
}
@ARTICLE{Suzuki2008,
author = {Suzuki, Tomo and Schirra, Frank and Richards, Stephen M. and Jensen,
Roderick V. and Sullivan, David A.},
title = {Estrogen and Progesterone Control of Gene Expression in the Mouse
Meibomian Gland},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {1797--1808},
number = {5},
month = may,
abstract = {PURPOSE. The purpose of the study was to test the hypothesis that
estrogen and progesterone regulate gene expression in the meibomian
gland. METHODS. Meibomian glands were obtained from young adult,
ovariectomized mice that were administered 17{beta}-estradiol, progesterone,
17{beta}-estradiol plus progesterone, or vehicle for 14 days. Glands
were pooled according to treatment, processed for the extraction
of RNA, and analyzed for differentially expressed mRNAs by using
mouse gene microarrays. Bioarray data were evaluated with sophisticated
bioinformatics software and statistical programs. The expression
of selected genes was confirmed with gene chips and quantitative
real-time PCR techniques. RESULTS. The findings show that 17{beta}-estradiol,
progesterone, or both hormones administered together significantly
influenced the expression of numerous genes in the mouse meibomian
gland. Notable were the effects of 17{beta}-estradiol on genes related
to lipid metabolism, tyrosine kinases, immune factors, extracellular
matrix components, steroidogenesis, and prolactin dynamics. Also
very significant were the actions of progesterone or 17{beta}-estradiol
plus progesterone on ribosome or localization gene ontologies, respectively.
The various hormone treatments led to many analogous, opposite, or
unique effects on gene expression. CONCLUSIONS. These findings support
the study hypothesis that estrogen and progesterone modulate gene
expression in the meibomian gland.},
url = {http://www.iovs.org/cgi/content/abstract/49/5/1797}
}
@ARTICLE{Suzuki2006a,
author = {Suzuki, Tomo and Schirra, Frank and Richards, Stephen M. and Treister,
Nathaniel S. and Lombardi, Michael J. and Rowley, Patricia and Jensen,
Roderick V. and Sullivan, David A.},
title = {Estrogen's and Progesterone's Impact on Gene Expression in the Mouse
Lacrimal Gland},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2006},
volume = {47},
pages = {158--168},
number = {1},
month = jan,
abstract = {PURPOSE. The hypothesis tested in the study was that the effect of
estrogen and progesterone on the lacrimal gland is mediated through
specific receptors and that hormonal effects involve the regulation
of gene expression and protein synthesis. METHODS. Lacrimal glands
were collected from young adult, ovariectomized mice, that were treated
with 17{beta}-estradiol, progesterone, 17{beta}-estradiol plus progesterone
or vehicle for 2 weeks. Glands were pooled according to treatment,
processed for the isolation of RNA, and evaluated for differentially
expressed mRNAs by using gene microarrays. Bioarray data were analyzed
with sophisticated bioinformatics and statistical programs. The expression
of selected genes was verified by using gene chips and quantitative
real-time PCR methods. RESULTS. The results demonstrate that 17{beta}-estradiol,
progesterone, or both hormones together significantly influences
the expression of hundreds of genes in the mouse lacrimal gland.
Sex steroid treatment led to numerous alterations in gene activities
related to transcriptional control, cell growth and/or maintenance,
cell communication, signal transduction, enzyme catalysis, immune
expression, and the binding and metabolism of nucleic acids and proteins.
A number of the 17{beta}-estradiol, progesterone or 17{beta}-estradiol
plus progesterone effects on gene expression were similar, but most
were unique to each treatment. Of particular interest was the finding
that these hormones seem to contribute little to the known sex-related
differences in gene expression of the lacrimal gland. CONCLUSIONS.
These results support the hypothesis that estrogen's and progesterone's
action on the lacrimal gland involves the regulation of numerous
genes. However, these hormone effects do not appear to represent
a major factor underlying the sexual dimorphism of gene expression
in lacrimal tissue.},
url = {http://www.iovs.org/cgi/content/abstract/47/1/158}
}
@ARTICLE{Suzuki2007a,
author = {Suzuki, Tatsuo and Tian, Qing Bao and Kuromitsu, Junro and Kawai,
Takatoshi and Endo, Shogo},
title = {Characterization of mRNA species that are associated with postsynaptic
density fraction by gene chip microarray analysis},
journal = {Neuroscience Research},
year = {2007},
volume = {57},
pages = {61--85},
number = {1},
month = jan,
abstract = {We previously reported the partial identification by random sequencing
of mRNA species that are associated with the postsynaptic density
(PSD) fraction prepared from the rat forebrain [Tian et al., 1999.
Mol. Brain Res. 72, 147-157]. We report here further characterization
by gene chip analysis of the PSD fraction-associated mRNAs, which
were prepared in the presence of RNase inhibitor. We found that mRNAs
encoding various postsynaptic proteins, such as channels, receptors
for neurotransmitters and neuromodulators, proteins involved in signaling,
scaffold and adaptor proteins and cytoskeletal proteins, were highly
concentrated in the PSD fraction, whereas those encoding housekeeping
proteins, such as enzymes in the glycolytic pathway, were not. We
extracted ~1900 mRNA species that were highly concentrated in the
PSD fraction. mRNAs related to certain neuronal diseases were also
enriched in the PSD fraction. We also constructed a cDNA library
using the PSD fraction-associated mRNAs as templates, and identified
1152 randomly selected clones by sequencing. Our data suggested that
the PSD fraction-associated mRNAs are a very useful resource, in
which a number of as yet uncharacterized mRNAs are concentrated.
Identification and functional characterization of them are essential
for complete understanding of synaptic function.},
issn = {0168-0102},
keywords = {Local protein synthesis, PSD, Dendrite, mRNA, Synaptic plasticity},
url = {http://www.sciencedirect.com/science/article/B6T0H-4M4KK03-2/2/4dd9367c15d521e1fa34804d53f6d4b5}
}
@ARTICLE{Svec2010,
author = {Svec, Jiri and Ergang, Peter and Mandys, Vaclav and Kment, Milan
and Pacha, Jiri},
title = {Expression profiles of proliferative and antiapoptotic genes in sporadic
and colitis-related mouse colon cancer models},
journal = {International Journal of Experimental Pathology},
year = {2010},
volume = {91},
pages = {44--53},
number = {1},
abstract = {Summary Elevated levels of survivin, telomerase catalytic subunit
(TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible
nitric oxide synthase (iNOS) and the regulatory factors c-MYB and
Tcf-4 are often found in human cancers including colorectal cancer
(CRC) and have been implicated in the development and progression
of tumorigenesis. The aim of this study was to determine the expression
of these genes in mouse models of sporadic and colitis-associated
CRC. To address these issues, we used qRT-PCR approach to determine
changes in gene expression patterns of neoplastic cells (high-grade
dysplasia/intramucosal carcinoma) and surrounding normal epithelial
cells in A/J and ICR mouse strains using laser microdissection. Both
strains were injected with azoxymethane and ICR mice were also given
drinking water that contained 2% dextran sodium sulphate. In both
sporadic (A/J mice) and colitis-associated (ICR mice) models of CRC,
the levels of TERT mRNA, COX-2 mRNA and Tcf-4 mRNA were higher in
neoplastic cells than in surrounding normal epithelial cells. In
contrast, survivin mRNA was upregulated only in neoplastic cells
from A/J mice and ILK mRNA was upregulated only in neoplastic cells
from ICR mice. However, the expression of iNOS mRNA was similar in
normal and neoplastic cells in both models and c-MYB mRNA was actually
downregulated in neoplastic cells compared with normal cells in both
models. These findings suggest that the genetic background and/or
the molecular mechanisms of tumorigenesis associated with genotoxic
insults and colonic inflammation influence the gene expression of
mTERT, COX-2, Tcf-4, c-MYB, ILK and survivin in colon epithelial
neoplasia.},
issn = {1365-2613},
keywords = {colon cancer, gene expression, mouse},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2613.2009.00698.x}
}
@ARTICLE{Svec2010a,
author = {Svec, Jiri and Musilkova, Jana and Bryndova, Jana and Jirasek, Tomas
and Mandys, Vaclav and Kment, Milan and Pacha, Jiri},
title = {Enhanced expression of proproliferative and antiapoptotic genes in
ulcerative colitis-associated neoplasia},
journal = {Inflamm Bowel Dis},
year = {2010},
volume = {16},
pages = {1127--1137},
number = {7},
abstract = {Abstract 10.1002/ibd.21178.abs Background: Inflammatory bowel diseases
including long-standing ulcerative colitis (UC) have an increased
risk of evolving into colorectal cancer (CRC). The overexpression
of some proproliferative and antiapoptotic genes, such as survivin,
telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK),
and regulatory factors c-MYB and Tcf-4, has been implicated in the
development and progression of several human malignancies including
CRC. Methods: In this study we analyzed the expression alterations
of these markers and proinflammatory enzymes cyclooxygenase 2 (COX-2)
and inducible nitric oxide synthase (iNOS) during the transition
of colonic mucosa from chronic inflammation to epithelial neoplasia
in biopsies of UC patients using quantitative real-time polymerase
chain reaction and immunohistochemistry; additionally, we compared
the expression profiles of this gene panel in samples of patients
with CRC after tumor resection and in human tumor xenografts of SW620
malignant colonic cells. Results: The transcript levels of survivin,
c-MYB, COX-2, iNOS, and Tcf-4 showed a statistically significant
increase during neoplastic transformation of UC patient colonic mucosa,
whereas hTERT and ILK were not elevated. In contrast, the specimens
of CRC showed upregulated expression of not only survivin, c-MYB,
Tcf-4, COX-2, and iNOS but also hTERT. A similar expression profile
was observed in human tumor xenografts in which all transcripts with
the exception of c-MYB were upregulated. Conclusions: These results
suggest that telomerase and ILK activation occurs during the later
stages of carcinoma progression, whereas upregulation of survivin,
c-MYB, and Tcf-4 is a feature of the early stage of development of
neoplasia, and thus, they might serve as early indicators for UC-associated
colorectal carcinogenesis. (Inflamm Bowel Dis 2010)},
issn = {1536-4844},
keywords = {ulcerative colitis, colorectal cancer, proproliferative and antiapoptotic
markers},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.21178}
}
@ARTICLE{Svensson2011,
author = {Svensson, Judit and Jenmalm, Maria C. and Matussek, Andreas and Geffers,
Robert and Berg, Goran and Ernerudh, Jan},
title = {Macrophages at the Fetal-Maternal Interface Express Markers of Alternative
Activation and Are Induced by M-CSF and IL-10},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {3671-3682},
number = {7},
abstract = {During pregnancy, the maternal immune system is challenged by the
presence of the fetus, which must be tolerated despite being semiallogeneic.
Uterine mucosal (or decidual) macrophages (M{phi}), one of the major
leukocyte populations at the fetal-maternal interface, have been
implicated in fetal tolerance, but information regarding their regulation
is scarce. In this study, we investigated the role of several factors
potentially involved in the differentiation and polarization of decidual
M{phi} with an in vitro M{phi} differentiation model. By using flow
cytometry, we showed that M-CSF and IL-10 were potent inducers of
M2 (immunoregulatory) M{phi} markers expressed on human decidual
M{phi} (CD14, CD163, CD206, CD209). In contrast, proinflammatory
stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13,
induced different patterns of expression, indicating that a Th2-dominated
environment is not required for decidual M{phi} polarization. M-CSF/IL-10-stimulated
and decidual M{phi} also showed similar cytokine secretion patterns,
with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely,
the proinflammatory, LPS/IFN-{gamma}-stimulated M{phi} produced significantly
higher levels of TNF and no IL-10. We also used a gene array with
420 M{phi}-related genes, of which 100 were previously reported to
be regulated in a global gene expression profiling of decidual M{phi},
confirming that M-CSF/IL-10-induced M{phi} are closely related to
decidual M{phi}. Taken together, our results consistently point to
a central role for M-CSF and in particular IL-10 in the shaping of
decidual M{phi} with regulatory properties. These cytokines may therefore
play an important role in supporting the homeostatic and tolerant
immune milieu required for a successful pregnancy.},
doi = {10.4049/jimmunol.1100130},
eprint = {http://www.jimmunol.org/cgi/reprint/187/7/3671.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/7/3671}
}
@ARTICLE{Svensson2006,
author = {Svensson, Jan T. and Crosatti, Cristina and Campoli, Chiara and Bassi,
Roberto and Stanca, Antonio Michele and Close, Timothy J. and Cattivelli,
Luigi},
title = {Transcriptome Analysis of Cold Acclimation in Barley Albina and Xantha
Mutants},
journal = {Plant Physiology},
year = {2006},
volume = {141},
pages = {257--270},
number = {1},
month = may,
abstract = {Previously, we have shown that barley (Hordeum vulgare) plants carrying
a mutation preventing chloroplast development are completely frost
susceptible as well as impaired in the expression of several cold-regulated
genes. Here we investigated the transcriptome of barley albina and
xantha mutants and the corresponding wild type to assess the effect
of the chloroplast on expression of cold-regulated genes. First,
by comparing control wild type against cold-hardened wild-type plants
2,735 probe sets with statistically significant changes (P = 0.05;
[≥]2-fold change) were identified. Expression of these wild-type
cold-regulated genes was then analyzed in control and cold-hardened
mutants. Only about 11% of the genes cold regulated in wild type
were regulated to a similar extent in all genotypes (chloroplast-independent
cold-regulated genes); this class includes many genes known to be
under C-repeat binding factor control. C-repeat binding factor genes
were also equally induced in mutants and wild-type plants. About
67% of wild-type cold-regulated genes were not regulated by cold
in any mutant (chloroplast-dependent cold-regulated genes). We found
that the lack of cold regulation in the mutants is due to the presence
of signaling pathway(s) normally cold activated in wild type but
constitutively active in the mutants, as well as to the disruption
of low-temperature signaling pathway(s) due to the absence of active
chloroplasts. We also found that photooxidative stress signaling
pathway is constitutively active in the mutants. These results demonstrate
the major role of the chloroplast in the control of the molecular
adaptation to cold.},
url = {http://www.plantphysiol.org/cgi/content/abstract/141/1/257}
}
@ARTICLE{Swafford2011,
author = {Swafford, Austin D.-E. and Howson, Joanna M.M. and Davison, Lucy
J. and Wallace, Chris and Smyth, Deborah J. and Schuilenburg, Helen
and Maisuria-Armer, Meeta and Mistry, Trupti and Lenardo, Michael
J. and Todd, John A.},
title = {An Allele of IKZF1 (Ikaros) Conferring Susceptibility to Childhood
Acute Lymphoblastic Leukemia Protects Against Type 1 Diabetes},
journal = {Diabetes},
year = {2011},
volume = {60},
pages = {1041--1044},
number = {3},
month = mar,
abstract = {OBJECTIVEIKZF1 encoding Ikaros, an essential regulator of lymphopoiesis
and immune homeostasis, has been implicated in the development of
childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide
association (GWA) studies have linked a region of the 3'-UTR of IKZF1
with C-ALL susceptibility, we tested whether IKZF1 is associated
with the autoimmune disease type 1 diabetes. RESEARCH DESIGN AND
METHODSrs10272724 (T>C) near IKZF1 at 7p12 was genotyped in 8,333
individuals with type 1 diabetes, 9,947 control subjects, and 3,997
families of European ancestry. Association was tested using logistic
regression in the case-control data and by the transmission disequilibrium
test in the families. Expression data for IKZF1 by rs10272724 genotype
were obtained using quantitative PCR of mRNA/cDNA generated from
peripheral blood mononuclear cells from 88 individuals, whereas expression
data for five other neighboring genes were obtained from the online
Genevar dataset. RESULTSThe minor allele of rs10272724 (C) was found
to be protective from type 1 diabetes (odds ratio 0.87 [95% CI 0.83-0.91];
P = 1.1 x 10-11). rs10272724 was not correlated with levels of two
transcripts of IKZF1 in peripheral blood mononuclear cells. CONCLUSIONSThe
major susceptibility genotype for C-ALL confers protection from type
1 diabetes. Our finding strengthens the link between autoimmunity
and lymphoid cancers. Further investigation is warranted for the
genetic effect marked by rs10272724, its impact on IKZF1, and the
role of Ikaros and other family members, Ailios (IKZF3) and Eos (IKZF4),
in autoimmunity.},
comment = {10.2337/db10-0446},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/60/3/1041}
}
@ARTICLE{Swain2011,
author = {Swain, Steve D and Meissner, Nicole N and Siemsen, Dan W and McInnerney,
Kate and Harmsen, Allen G},
title = {Pneumocystis elicits a STAT6-dependent strain specific innate immune
response and airway hyperresponsiveness},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2011},
pages = {2011-0154OC},
abstract = {It is widely held that exposure to pathogens such as fungi can be
an agent of co-morbidity, such as exacerbation of asthma or COPD.
While many studies have examined allergic responses to fungi and
their effects on pulmonary function, possible pathologic implications
of the early innate responses to fungal pathogens has not been explored.
We examined early responses to the atypical fungus Pneumocystis in
two common strains of mice, in terms of overall immunological response
and related pathology such as cell damage and airway hyperresponsiveness
(AHR). We found a strong strain-specific response in BALB/c mice
that included recruitment of neutrophils, NK, NKT, and CD4 T cells.
This response was accompanied by elevated indicators of lung damage
(BALF albumin and LDH), and a profound AHR. This early response was
absent in C57BL/6 mice, although both strains exhibited a later response
associated with the clearance of Pneumocystis. We found that this
AHR could not be attributed exclusively to the presence of recruited
neutrophils, NKT, NK or CD4 cells, or to the actions of IFN-{gamma}
or IL-4. However, in the absence of STAT6 signaling, both AHR and
inflammatory cell recruitment was virtually absent. Interestingly,
gene expression analysis indicated that this early response also
included activation of several transcription factors that could be
involved in pulmonary remodeling. These results show that exposure
to a fungus such as Pneumocystis can elicit pulmonary responses that
may contribute to morbidity, even without prior sensitization, in
the context of certain genetic backgrounds.},
doi = {10.1165/rcmb.2011-0154OC},
eprint = {http://ajrcmb.atsjournals.org/cgi/reprint/2011-0154OCv1.pdf},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/2011-0154OCv1}
}
@ARTICLE{Swainston2010,
author = {Swainston, Neil and Golebiewski, Martin and Messiha, Hanan L. and
Malys, Naglis and Kania, Renate and Kengne, Sylvestre and Krebs,
Olga and Mir, Saqib and Sauer-Danzwith, Heidrun and Smallbone, Kieran
and Weidemann, Andreas and Wittig, Ulrike and Kell, Douglas B. and
Mendes, Pedro and Müller, Wolfgang and Paton, Norman W. and Rojas,
Isabel},
title = {Enzyme kinetics informatics: from instrument to browser},
journal = {FEBS Journal},
year = {2010},
volume = {277},
pages = {3769--3779},
number = {18},
abstract = {A limited number of publicly available resources provide access to
enzyme kinetic parameters. These have been compiled through manual
data mining of published papers, not from the original, raw experimental
data from which the parameters were calculated. This is largely due
to the lack of software or standards to support the capture, analysis,
storage and dissemination of such experimental data. Introduced here
is an integrative system to manage experimental enzyme kinetics data
from instrument to browser. The approach is based on two interrelated
databases: the existing SABIO-RK database, containing kinetic data
and corresponding metadata, and the newly introduced experimental
raw data repository, MeMo-RK. Both systems are publicly available
by web browser and web service interfaces and are configurable to
ensure privacy of unpublished data. Users of this system are provided
with the ability to view both kinetic parameters and the experimental
raw data from which they are calculated, providing increased confidence
in the data. A data analysis and submission tool, the kineticswizard,
has been developed to allow the experimentalist to perform data collection,
analysis and submission to both data resources. The system is designed
to be extensible, allowing integration with other manufacturer instruments
covering a range of analytical techniques.},
issn = {1742-4658},
keywords = {data analysis, database, enzyme, kinetics, metadata},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1742-4658.2010.07778.x}
}
@ARTICLE{Swamynathan2008,
author = {Swamynathan, Shivalingappa K. and Davis, Janine and Piatigorsky,
Joram},
title = {Identification of Candidate Klf4 Target Genes Reveals the Molecular
Basis of the Diverse Regulatory Roles of Klf4 in the Mouse Cornea},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {3360--3370},
number = {8},
month = aug,
abstract = {PURPOSE. Kruppel-like factor 4 (Klf4) plays a crucial role in the
development and maintenance of the mouse cornea. In the current study,
wild-type (WT) and Klf4-conditional null (Klf4CN) corneal gene expression
patterns were examined, to gain understanding of the molecular basis
of the Klf4CN corneal phenotype. METHODS. Expression of more than
22,000 genes in 10 WT and Klf4CN corneas was compared by microarrays,
analyzed using BRB ArrayTools (National Cancer Institute, Bethesda,
MD) and validated by Q-RT-PCR. Transient cotransfections were used
to test whether Klf4 activates the aquaporin-3, Aldh3a1, and TKT
promoters. RESULTS. Scatterplot analysis identified 740 and 529 genes
up- and downregulated by more than twofold, respectively, in the
Klf4CN corneas. Cell cycle activators were upregulated, whereas the
inhibitors were downregulated, consistent with the increased Klf4CN
corneal epithelial cell proliferation. Desmosomal components were
downregulated, consistent with the Klf4CN corneal epithelial fragility.
Downregulation of aquaporin-3, detected by microarray, was confirmed
by immunoblot and immunohistochemistry. Aquaporin-3 promoter activity
was stimulated 7- to 10-fold by cotransfection with pCI-Klf4. The
corneal crystallins Aldh3A1 and TKT were downregulated in the Klf4CN
cornea, and their respective promoter activities were upregulated
16- and 9-fold by pCI-Klf4 in cotransfections. The expression of
epidermal keratinocyte differentiation markers was affected in the
Klf4CN cornea. Although the cornea-specific keratin-12 was downregulated,
most other keratins were upregulated, suggesting hyperkeratosis.
CONCLUSIONS. Functionally diverse candidate Klf4 target genes were
identified, revealing the molecular basis of the diverse aspects
of the Klf4CN corneal phenotype. These results establish Klf4 as
an important node in the genetic network of transcription factors
regulating the corneal homeostasis.},
url = {http://www.iovs.org/cgi/content/abstract/49/8/3360}
}
@ARTICLE{Swanson2011,
author = {Swanson, Todd A. and Krueger, Sarah A. and Galoforo, Sandra and Thibodeau,
Bryan J. and Martinez, Alvaro A. and Wilson, George D. and Marples,
Brian},
title = {TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness
in cell culture models of androgen independent prostate cancer},
journal = {The Prostate},
year = {2011},
volume = {71},
pages = {1548--1558},
number = {14},
abstract = {PURPOSE/OBJECTIVESThe androgen regulated transmembrane serine protease
(TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong
prognostic factor for disease recurrence following prostatectomy.
Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts
is linked with tumor proliferation, invasion, and an aggressive phenotype.
The aim of this study was to define the effect of TMPRSS2/ERG fusion
gene expression on chemo- and radiosensitivity in prostate tumor
cell lines.MATERIALS/METHODSClonogenic survival of PC3 and DU145
cells stably expressing TMPRSS2/ERG Types III and VI fusion genes
was measured after X-irradiation (0–8 Gy) and Paclitaxel. Cell
cycle changes and DNA double-strand break induction and repair were
assessed. Differential gene expression was measured by microarray
analysis. ERG signaling pathway interactions were studied using Ariadne
Pathway Studio.RESULTSExpression of the TMPRSS2/ERG fusions in PC3
cells increased radiation sensitivity and decreased paclitaxel sensitivity.
Increased radiosensitivity was associated with persistent DNA breaks
24 hr post-irradiation, down-regulation of genes involved in DNA
repair and mitosis and up-regulation of ETV, an ETS transcription
factor. However, DU145 Types III and VI demonstrated a different
sensitivity phenotype and gene expression changes. Pathway analysis
of ERG signaling further illustrated the variation between the PC3
and DU145 cell lines containing TMPRSS2/ERG fusions.CONCLUSIONSThe
effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity
and chemosensitivity depending on cell line and fusion type. Further
work is needed with clinical samples to establish whether TMPRSS2/ERG
gene fusions affect radio- and chemosensitivity in vivo. Prostate
71:1548–1558, 2011. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/pros.21371},
issn = {1097-0045},
keywords = {prostate, cell lines, TMPRSS2/ERG, radiosensitivity, paclitaxel},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.21371}
}
@ARTICLE{Swarbrick2008,
author = {Swarbrick, P. J. and Huang, K. and Liu, G. and Slate, J. and Press,
M. C. and Scholes, J. D.},
title = {Global patterns of gene expression in rice cultivars undergoing a
susceptible or resistant interaction with the parasitic plant Striga
hermonthica},
journal = {New Phytologist},
year = {2008},
volume = {179},
pages = {515--529},
number = {2},
abstract = {Summary * • Striga hermonthica is a root hemiparasite of cereals
that causes devastating loss of yield. Recently, a rice cultivar,
Nipponbare, was discovered, which exhibits post-attachment resistance
to this parasite and quantitative trait loci (QTL) associated with
the resistance were identified. * • Changes in gene expression
in susceptible (IAC 165) and resistant (Nipponbare) rice cultivars
were profiled using rice whole-genome microarrays. In addition to
a functional categorization of changes in gene expression, genes
that were significantly up-regulated within resistance QTL were identified.
* • The resistance reaction was characterized by up-regulation
of defence genes, including pathogenesis-related proteins, pleiotropic
drug resistance ABC transporters, genes involved in phenylpropanoid
metabolism and WRKY transcription factors. These changes in gene
expression resemble those associated with resistance to microbial
pathogens. Three genes encoding proteins of unknown function, within
a major resistance QTL on chromosome 12, were highly up-regulated
and are excellent candidate resistance genes. * • The susceptible
interaction was characterized by large-scale down-regulation of gene
expression, particularly within the functional categories plant growth
regulator signalling and metabolism, biogenesis of cellular components
and cell division. Up-regulated genes included nutrient transporters,
enzymes of amino acid metabolism and some abiotic stress genes.},
issn = {1469-8137},
keywords = {gene expression, microarray, quantitative trait loci (QTL), resistant,
susceptible, Striga},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2008.02484.x}
}
@ARTICLE{Swarup2011,
author = {Swarup, Vivek and Phaneuf, Daniel and Bareil, Christine and Robertson,
Janice and Rouleau, Guy A. and Kriz, Jasna and Julien, Jean-Pierre},
title = {Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal
lobar degeneration in transgenic mice produced with TDP-43 genomic
fragments},
journal = {Brain},
year = {2011},
volume = {134},
pages = {2610-2626},
number = {9},
abstract = {Transactive response DNA-binding protein 43 ubiquitinated inclusions
are a hallmark of amyotrophic lateral sclerosis and of frontotemporal
lobar degeneration with ubiquitin-positive inclusions. Yet, mutations
in TARDBP, the gene encoding these inclusions are associated with
only 3% of sporadic and familial amyotrophic lateral sclerosis. Recent
transgenic mouse studies have revealed a high degree of toxicity
due to transactive response DNA-binding protein 43 proteins when
overexpressed under the control of strong neuronal gene promoters,
resulting in early paralysis and death, but without the presence
of amyotrophic lateral sclerosis-like ubiquitinated transactive response
DNA-binding protein 43-positive inclusions. To better mimic human
amyotrophic lateral sclerosis, we generated transgenic mice that
exhibit moderate and ubiquitous expression of transactive response
DNA-binding protein 43 species using genomic fragments that encode
wild-type human transactive response DNA-binding protein 43 or familial
amyotrophic lateral sclerosis-linked mutant transactive response
DNA-binding protein 43 (G348C) and (A315T). These novel transgenic
mice develop many age-related pathological and biochemical changes
reminiscent of human amyotrophic lateral sclerosis including ubiquitinated
transactive response DNA-binding protein 43-positive inclusions,
transactive response DNA-binding protein 43 cleavage fragments, intermediate
filament abnormalities, axonopathy and neuroinflammation. All three
transgenic mouse models (wild-type, G348C and A315T) exhibited impaired
learning and memory capabilities during ageing, as well as motor
dysfunction. Real-time imaging with the use of biophotonic transactive
response DNA-binding protein 43 transgenic mice carrying a glial
fibrillary acidic protein-luciferase reporter revealed that the behavioural
defects were preceded by induction of astrogliosis, a finding consistent
with a role for reactive astrocytes in amyotrophic lateral sclerosis
pathogenesis. These novel transactive response DNA-binding protein
43 transgenic mice mimic several characteristics of human amyotrophic
lateral sclerosis-frontotemporal lobar degeneration and they should
provide valuable animal models for testing therapeutic approaches.},
doi = {10.1093/brain/awr159},
eprint = {http://brain.oxfordjournals.org/cgi/reprint/134/9/2610.pdf},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/134/9/2610}
}
@ARTICLE{Swarup2011a,
author = {Swarup, Vivek and Phaneuf, Daniel and Dupre, Nicolas and Petri, Susanne
and Strong, Michael and Kriz, Jasna and Julien, Jean-Pierre},
title = {Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers
nuclear factor {kappa}B-mediated pathogenic pathways},
journal = {J. Exp. Med.},
year = {2011},
volume = {208},
pages = {2429-2447},
number = {12},
abstract = {TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic
lateral sclerosis (ALS). In this study, we report that TDP-43 and
nuclear factor {kappa}B (NF-{kappa}B) p65 messenger RNA and protein
expression is higher in spinal cords in ALS patients than healthy
individuals. TDP-43 interacts with and colocalizes with p65 in glial
and neuronal cells from ALS patients and mice expressing wild-type
and mutant TDP-43 transgenes but not in cells from healthy individuals
or nontransgenic mice. TDP-43 acted as a co-activator of p65, and
glial cells expressing higher amounts of TDP-43 produced more proinflammatory
cytokines and neurotoxic mediators after stimulation with lipopolysaccharide
or reactive oxygen species. TDP-43 overexpression in neurons also
increased their vulnerability to toxic mediators. Treatment of TDP-43
mice with Withaferin A, an inhibitor of NF-{kappa}B activity, reduced
denervation in the neuromuscular junction and ALS disease symptoms.
We propose that TDP-43 deregulation contributes to ALS pathogenesis
in part by enhancing NF-{kappa}B activation and that NF-{kappa}B
may constitute a therapeutic target for the disease.},
doi = {10.1084/jem.20111313},
eprint = {http://jem.rupress.org/cgi/reprint/208/12/2429.pdf},
url = {http://jem.rupress.org/cgi/content/abstract/208/12/2429}
}
@ARTICLE{Swayze2007,
author = {Swayze, Eric E. and Siwkowski, Andrew M. and Wancewicz, Edward V.
and Migawa, Michael T. and Wyrzykiewicz, Tadeusz K. and Hung, Gene
and Monia, Brett P. and Bennett and Frank, C.},
title = {Antisense oligonucleotides containing locked nucleic acid improve
potency but cause significant hepatotoxicity in animals},
journal = {Nucleic Acids Res.},
year = {2007},
volume = {35},
pages = {687--700},
number = {2},
month = jan,
abstract = {A series of antisense oligonucleotides (ASOs) containing either 2'-O-methoxyethylribose
(MOE) or locked nucleic acid (LNA) modifications were designed to
investigate whether LNA antisense oligonucleotides (ASOs) have the
potential to improve upon MOE based ASO therapeutics. Some, but not
all, LNA containing oligonucleotides increased potency for reducing
target mRNA in mouse liver up to 5-fold relative to the corresponding
MOE containing ASOs. However, they also showed profound hepatotoxicity
as measured by serum transaminases, organ weights and body weights.
This toxicity was evident for multiple sequences targeting three
different biological targets, as well as in mismatch control sequences
having no known mRNA targets. Histopathological evaluation of tissues
from LNA treated animals confirmed the hepatocellular involvement.
Toxicity was observed as early as 4 days after a single administration.
In contrast, the corresponding MOE ASOs showed no evidence for toxicity
while maintaining the ability to reduce target mRNA. These studies
suggest that while LNA ASOs have the potential to improve potency,
they impose a significant risk of hepatotoxicity.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/35/2/687}
}
@ARTICLE{Swiatecka-Urban2007,
author = {Swiatecka-Urban, Agnieszka and Talebian, Laleh and Kanno, Eiko and
Moreau-Marquis, Sophie and Coutermarsh, Bonita and Hansen, Karyn
and Karlson, Katherine H. and Barnaby, Roxanna and Cheney, Richard
E. and Langford, George M. and Fukuda, Mitsunori and Stanton, Bruce
A.},
title = {Myosin Vb Is Required for Trafficking of the Cystic Fibrosis Transmembrane
Conductance Regulator in Rab11a-specific Apical Recycling Endosomes
in Polarized Human Airway Epithelial Cells},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {23725--23736},
number = {32},
month = aug,
abstract = {Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated
Cl- secretion across fluid-transporting epithelia is regulated, in
part, by modulating the number of CFTR Cl- channels in the plasma
membrane by adjusting CFTR endocytosis and recycling. However, the
mechanisms that regulate CFTR recycling in airway epithelial cells
remain unknown, at least in part, because the recycling itineraries
of CFTR in these cells are incompletely understood. In a previous
study, we demonstrated that CFTR undergoes trafficking in Rab11a-specific
apical recycling endosomes in human airway epithelial cells. Myosin
Vb is a plus-end-directed, actin-based mechanoenzyme that facilitates
protein trafficking in Rab11a-specific recycling vesicles in several
cell model systems. There are no published studies examining the
role of myosin Vb in airway epithelial cells. Thus, the goal of this
study was to determine whether myosin Vb facilitates CFTR recycling
in polarized human airway epithelial cells. Endogenous CFTR formed
a complex with endogenous myosin Vb and Rab11a. Silencing myosin
Vb by RNA-mediated interference decreased the expression of wild-type
CFTR and {Delta}F508-CFTR in the apical membrane and decreased CFTR-mediated
Cl- secretion across polarized human airway epithelial cells. A recombinant
tail domain fragment of myosin Vb attenuated the plasma membrane
expression of CFTR by arresting CFTR recycling. The dominant-negative
effect was dependent on the ability of the myosin Vb tail fragment
to interact with Rab11a. Taken together, these data indicate that
myosin Vb is required for CFTR recycling in Rab11a-specific apical
recycling endosomes in polarized human airway epithelial cells.},
url = {http://www.jbc.org/cgi/content/abstract/282/32/23725}
}
@ARTICLE{Swiatek-DeLange2007,
author = {Swiatek-De Lange, Magdalena and Stampfl, Andreas and Hauck, Stefanie
M. and Zischka, Hans and Gloeckner, Christian J. and Deeg, Cornelia
A. and Ueffing, Marius},
title = {Membrane-initiated effects of progesterone on calcium dependent signaling
and activation of VEGF gene expression in retinal glial cells},
journal = {Glia},
year = {2007},
volume = {55},
pages = {1061--1073},
number = {10},
abstract = {Abstract 10.1002/glia.20523.abs Neurosteroids, such as progesterone,
influence central nervous system development and function by regulating
a broad spectrum of physiological processes. Here, we investigated
membrane-initiated actions of progesterone in the retina and identified
the membrane-associated progesterone receptor component 1 (PGRMC1).
We found PGRMC1 expressed mainly in retinal Muller glia (RMG) and
retinal pigment epithelium, and localized uniquely to microsomal
and plasma membrane fractions. In RMG, membrane-impermeable progesterone
conjugate induced calcium influx and subsequent phosphatidylinositol
3-kinase-mediated phosphorylation of PKC and ERK-1/2. Induction by
progesterone also led to PKC-dependent activation of VEGF gene expression
and protein synthesis, suggesting a contribution of membrane-initiated
hormone effects to VEGF induced neovascularization within retina.
© 2007 Wiley-Liss, Inc.},
issn = {1098-1136},
keywords = {neurosteroids, transmembrane receptor, intracellular calcium, retinal
glial cells},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.20523}
}
@ARTICLE{Swiderek2007,
author = {Swiderek, Halina and Al-Rubeai, Mohamed},
title = {Functional genome-wide analysis of antibody producing NS0 cell line
cultivated at different temperatures},
journal = {Biotechnol. Bioeng.},
year = {2007},
volume = {98},
pages = {616--630},
number = {3},
abstract = {Abstract 10.1002/bit.21445.abs Lowering culture temperature has been
reported as a significant factor in the improvement of mammalian
cell productivity. To determine the physiological changes which take
place at different temperature cultivations, an NS0 cell line producing
human-mouse chimeric antibody was cultured at 22, 34 and 37°C. Various
cellular parameters such as viability, productivity, metabolism,
apoptosis and cell cycle were studied and notable changes were shown
to be accompanied by changes in metabolic rates. Reduction of the
temperature to 22°C resulted in a decrease in the growth rate, inhibition
of antibody production, arrest of cell cycle in G2 phase and delay
in apoptosis. A slight increase in antibody production was observed
at 34°C due to the increase of growth rate and prolonged stationary
phase. To better understand and explore the mechanisms underpinning
these biological alterations and to identify the genes involved in
the genetic reprogramming, genome-wide analyses were performed using
GeneChip Mouse Genome arrays. The examination of differential gene
expression induced by temperature reduction demonstrated a specific
pattern of gene expression in NS0 cells in response to temperature
stress. The effect of temperature on transcription induced changes
within a wide range of genes involved in metabolic and signalling
pathways. Most deregulated genes involved in essential metabolic
pathways (i.e. glycolysis/gluconeogenesis, pentose phosphate pathway
and inositol metabolism) were repressed in cells cultured at 22°C.
By combining gene expression and physiological changes at different
temperatures it was possible to provide greater understanding of
cell response to hypothermic conditions. Biotechnol. Bioeng. 2007;98:
616–630. © 2007 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {cell culture, NS0, genomics, microarrays, gene expression, low temperature},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.21445}
}
@ARTICLE{Swiderek2008,
author = {Swiderek, Halina and Logan, Anna and Al-Rubeai, Mohamed},
title = {Cellular and transcriptomic analysis of NS0 cell response during
exposure to hypoxia},
journal = {Journal of Biotechnology},
year = {2008},
volume = {134},
pages = {103--111},
number = {1-2},
month = mar,
abstract = {Mammalian cells have the ability to alter their gene expression in
order to survive or adapt to a variety of environment stresses including
hypoxic stress. Maintaining oxygen supply has been accepted as essential
for cell survival and growth. To determine the cellular and molecular
changes which take place under oxygen deprivation, an NS0 cell line
producing a human-mouse chimeric antibody was cultured under hypoxic
conditions (<1%). Various cellular parameters such as viability,
productivity, metabolism, apoptosis and cell cycle were studied and
notable changes were shown to be accompanied by changes in metabolic
rates. When the cells where exposed to hypoxia for 48 h, cell growth
was suppressed and cell death was detected. To better understand
and explore the mechanisms underpinning these biological alterations
and to identify the genes involved in the genetic reprogramming,
genome-wide analyses were performed using GeneChip Mouse Genome arrays.
The gene expression profiling generated by the microarray technique
revealed that hypoxia, even in the early stages (12 h), induces significant
changes in gene expression in NS0 cells. The primary responses to
hypoxia within the cells were: (1) the up-regulation of pathways
such as glycolysis that ultimately lead to alternative routes of
ATP generation and increased oxygen availability; and (2) the down-regulation
of genes involved in purine/pyrimidine and one carbon pool metabolisms
required for DNA and RNA synthesis. By combining gene expression
and physiological changes under hypoxia, it was possible to explore
the mechanisms of hypoxia-induced alterations in more depth.},
issn = {0168-1656},
keywords = {Cell culture, NS0, Genomics, Microarrays, Gene expression, Hypoxia},
url = {http://www.sciencedirect.com/science/article/B6T3C-4RKMHTW-2/2/754a502ab91fd4f15fb3ada81b799b66}
}
@ARTICLE{Swiderski2007,
author = {Swiderski, Ruth E. and Nishimura, Darryl Y. and Mullins, Robert F.
and Olvera, Marissa A. and Ross, Jean L. and Huang, Jian and Stone,
Edwin M. and Sheffield, Val C.},
title = {Gene Expression Analysis of Photoreceptor Cell Loss in Bbs4-Knockout
Mice Reveals an Early Stress Gene Response and Photoreceptor Cell
Damage},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {3329--3340},
number = {7},
month = jul,
abstract = {PURPOSE. To identify and characterize gene expression changes associated
with photoreceptor cell loss in a Bbs4-knockout mouse model of retinal
degeneration. METHODS. Differential gene expression in the eyes of
5-month-old Bbs4-/- mice undergoing retinal degeneration were analyzed
using gene microarrays (Affymetrix, Santa Clara, CA). Elevated ocular
transcripts were confirmed by Northern blotting of RNA from Bbs4-/-
and three additional mouse models of Bardet-Biedl Syndrome (BBS).
TUNEL assays and transmission electron microscopy were used to study
cell death and photoreceptor morphology in these mice. RESULTS. Three
hundred fifty-four probes were differentially expressed in Bbs4-/-
eyes compared with controls using a twofold cutoff. Numerous vision-related
transcripts decreased because of photoreceptor cell loss. Increased
expression of the stress response genes Edn2, Lcn2, Serpina3n, and
Socs3 was noted at 5 months of age and as early as postnatal week
4 in the eyes of four BBS mouse model strains. A burst of apoptotic
activity in the photoreceptor outer nuclear layer at postnatal week
2 and highly disorganized outer segments by postnatal weeks 4 to
6 was observed in all four strains. CONCLUSIONS. The specific loss
of photoreceptors in Bbs4-/- mice allows us to identify a set of
genes that are preferentially expressed in photoreceptors compared
with other cell types found in the eye and is a valuable resource
in the continuing search for genes involved in retinal disease. The
molecular and morphologic changes observed in young BBS animal model
eyes implies that BBS proteins play a critical, early role in establishing
the correct structure and function of photoreceptors.},
url = {http://www.iovs.org/cgi/content/abstract/48/7/3329}
}
@ARTICLE{Swift2008,
author = {Swift, Steven M. and Gaume, Brigitte R. and Small, Kersten M. and
Aronow, Bruce J. and Liggett, Stephen B.},
title = {Differential coupling of Arg- and Gly389 polymorphic forms of the
{beta}1-adrenergic receptor leads to pathogenic cardiac gene regulatory
programs},
journal = {Physiol Genomics},
year = {2008},
volume = {35},
pages = {123--131},
number = {1},
month = sep,
abstract = {The {beta}1-adrenergic receptor ({beta}1AR; ADRB1) polymorphism Arg389Gly
is located in an intracellular loop and is associated with distinct
human and mouse cardiovascular phenotypes. To test the hypothesis
that {beta}1-Arg389 and {beta}1-Gly389 alleles could differentially
couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP
signaling, we performed comparative gene expression profile analyses
on hearts from wild-type and transgenic mice that expressed either
human {beta}1-Arg389 or {beta}1-Gly389 receptors, or AC5, sampling
at an early age prior to the onset of pathological features. All
three models upregulated the expression of genes associated with
RNA metabolism and translation and downregulated genes associated
with mitochondria and energy metabolism, consistent with shared cAMP-driven
increase in cardiac contractility, protein synthesis, and compensatory
downregulation of mitochondrial energy production. Both {beta}1AR
alleles activated additional genes associated with other pathways.
Uniquely, {beta}1-Arg389 hearts exhibited upregulated expression
of genes associated with inflammation, programmed cell death, and
extracellular matrix. These observations expand the scope of 7-transmembrane
domain receptor signaling propagation beyond known cognate G protein
couplings. Moreover, they implicate alterations of a repertoire of
processes evoked by a single amino acid variation in the cardiac
{beta}1AR that might be exploited for genotype-specific heart failure
diagnostics and therapeutics.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/35/1/123}
}
@BOOK{Syagailo2008,
title = {Microarray-based Expression Profiling: From Technological Basics
to Diagnostic Perspectives},
publisher = {Wiley-VCH Verlag GmbH},
year = {2008},
author = {Syagailo, Yana V. and Kusnezow, Wlad and Hoheisel, Jörg D.},
pages = {728--754},
abstract = {Summary 10.1002/9783527619665.ch28.abs This chapter contains sections
titled:},
booktitle = {Apoptosis and Cancer Therapy},
issn = {9783527619665},
keywords = {microarray, expression profiling, diagnostic perspectives, prognostic
techniques, molecular components},
url = {http://dx.doi.org/10.1002/9783527619665.ch28}
}
@ARTICLE{Syed2010,
author = {Syed, Farhan A and Mödder, Ulrike IL and Roforth, Matthew and Hensen,
Ira and Fraser, Daniel G and Peterson, James M and Oursler, Merry
Jo and Khosla, Sundeep},
title = {Effects of chronic estrogen treatment on modulating age-related bone
loss in female mice},
journal = {J Bone Miner Res},
year = {2010},
volume = {25},
pages = {2438--2446},
number = {11},
abstract = {Abstract While female mice do not have the equivalent of a menopause,
they do undergo reproductive senescence. Thus, to dissociate the
effects of aging versus estrogen deficiency on age-related bone loss,
we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced
female C57/BL6 mice at 6 months of age and followed them to age 18
to 22 months. Lumbar spines and femurs were excised for analysis,
and bone marrow hematopoietic lineage negative (lin–) cells (enriched
for osteoprogenitor cells) were isolated for gene expression studies.
Six-month-old intact control mice were euthanized to define baseline
parameters. Compared with young mice, aged/sham-operated mice had
a 42% reduction in lumbar spine bone volume/total volume (BV/TV),
and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated
mice did not prevent age-related trabecular bone loss at this site.
By contrast, lifelong estrogen treatment of ovariectomized mice completely
prevented the age-related reduction in cortical volumetric bone mineral
density (vBMD) and thickness at the tibial diaphysis present in the
aged/sham-operated mice. As compared with cells from young mice,
lin– cells from aged/sham-operated mice expressed significantly
higher mRNA levels for osteoblast differentiation and proliferation
marker genes. These data thus demonstrate that, in mice, age-related
loss of cortical bone in the appendicular skeleton, but not loss
of trabecular bone in the spine, can be prevented by maintaining
constant estrogen levels over life. The observed increase in osteoblastic
differentiation and proliferation marker gene expression in progenitor
bone marrow cells from aged versus young mice may represent a compensatory
mechanism in response to ongoing bone loss. © 2010 American Society
for Bone and Mineral Research.},
issn = {1523-4681},
keywords = {aging, estrogen, bone, mice, ovariectomy},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jbmr.129}
}
@ARTICLE{Sylla2006,
author = {Sylla, Patricia and Nihalani, Anish and Whelan, Richard L.},
title = {Microarray analysis of the differential effects of open and laparoscopic
surgery on murine splenic T-cells},
journal = {Surgery},
year = {2006},
volume = {139},
pages = {92--103},
number = {1},
month = jan,
abstract = {Background Surgical trauma depresses cell-mediated immunity of a duration
and magnitude proportional to the degree of injury. However, the
cellular mechanism underlying this effect is poorly understood. Microarrays
were used to survey gene expression in murine splenic T-cells after
pneumoperitoneum and laparotomy.Methods C3H/HeJ mice were assigned
randomly to undergo anesthesia alone, sham laparotomy, or CO2 pneumoperitoneum
and sacrificed 12 or 24 hours later. RNA was isolated from purified
splenic T-cells and hybridized to Affymetrix oligonucleotide microarrays.Results
Relative to anesthesia, 116 genes after pneumoperitoneum and 398
genes after laparotomy showed a >=2-fold change in expression at
12 hours. One hundred thirty-two genes after pneumoperitoneum and
157 genes after laparotomy met those criteria at 24 hours. Comparing
surgical modalities, 177 genes were increased and 15 decreased >=2-fold
after laparotomy relative to pneumoperitoneum at 12 hours, compared
with 44 and 5 genes respectively at 24 hours. Expression changes
for 8 genes were validated by quantitative real-time polymerase chain
reaction.Conclusions Laparotomy and pneumoperitoneum alter splenic
T-cell gene expression, with the most extensive changes occurring
12 hours after laparotomy. This study is one of the first comprehensive
genomic studies of the molecular effects of surgical manipulation
on immune function. The genes identified are potential targets for
modulating the immune response to surgery.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4HTPV1G-N/2/786125b6a59a4a678a1c9f73f819ccea}
}
@ARTICLE{Sylvius2011,
author = {Sylvius, Nicolas and Bonne, Gisele and Straatman, Kees and Reddy,
Thimma and Gant, Timothy W. and Shackleton, Sue},
title = {MicroRNA expression profiling in patients with lamin A/C-associated
muscular dystrophy},
journal = {FASEB J},
year = {2011},
volume = {25},
pages = {3966-3978},
number = {11},
abstract = {Mutations in the lamin A/C gene (LMNA) cause several disorders referred
to as laminopathies, which include premature aging syndromes, lipodystrophy,
and striated muscle disorders. There is evidence that lamin A/C plays
a role in gene expression. MicroRNAs (miRNAs) are short noncoding
RNAs regulating mRNAs involved in various biological processes, including
the pathophysiology of striated muscles. Here, we profiled the expression
of the miRNA transcriptome in skeletal muscle from patients with
LMNA-related muscular dystrophy. Results show that control and patient
groups can be distinguished based on their miRNA expression profile.
Sixteen miRNAs are significantly dysregulated in patients compared
with controls. Pathway enrichment analysis in the predicted targets
of these miRNAs revealed pathways involved in muscle repair, such
as MAPK, transforming growth factor-{beta}, and Wnt signaling. Interestingly,
9 of these miRNAs (hsa-miR-100, -127-3p, -148a, -136*, -192, -335,
-376c, -489, and -502-3p) are highly expressed in fetal muscle, suggesting
that the fetal miRNA gene program mediates a regenerative process.
Overexpression of these miRNAs in C2C12 mouse myoblasts revealed
that 3 of them (miR-100, -192, and -335) participate in muscle proliferation
and differentiation. We identified target genes that likely mediate
this effect, which include the calcineurin gene PPP3CA. Our findings
are the first to demonstrate that miRNA expression is affected in
laminopathies.--Sylvius, N., Bonne, G., Straatman, K., Reddy, T.,
Gant, T. W., Shackleton, S. MicroRNA expression profiling in patients
with lamin A/C-associated muscular dystrophy.},
doi = {10.1096/fj.11-182915},
eprint = {http://www.fasebj.org/cgi/reprint/25/11/3966.pdf},
url = {http://www.fasebj.org/cgi/content/abstract/25/11/3966}
}
@ARTICLE{Symmans2003,
author = {Symmans, W. Fraser and Ayers, Mark and Clark, Edwin A. and Stec,
James and Hess, Kenneth R. and Sneige, Nour and Buchholz, Thomas
A. and Krishnamurthy, Savitri and Ibrahim, Nuhad K. and Buzdar, Aman
U. and Theriault, Richard L. and Rosales, Marguerite F.M. and Thomas,
Eva S. and Gwyn, Karin M. and Green, Marjorie C. and Syed, Abdul
R. and Hortobagyi, Gabriel N. and Pusztai, Lajos},
title = {Total RNA yield and microarray gene expression profiles from fine-needle
aspiration biopsy and core-needle biopsy samples of breast carcinoma},
journal = {Cancer},
year = {2003},
volume = {97},
pages = {2960--2971},
number = {12},
abstract = {Abstract 10.1002/cncr.11435.abs BACKGROUND Gene expression profiling
should be applicable to needle biopsy samples if microarray technology
is to become practically useful for clinical research or management
of breast carcinoma. This study compared gene expression profiles
derived from fine-needle aspiration biopsy (FNAB) and from core needle
biopsy (CBX). METHODS Total RNA was extracted from single FNAB and
CBX samples. Corresponding pairs of FNAB and CBX were analyzed for
similarity of gene expression profiles using cDNA microarrays that
contain 30,721 human sequences. A subset of genes that distinguished
CBX samples from FNAB samples was evaluated in a larger group of
needle biopsy samples and in a published genomic database derived
from 78 sporadic breast carcinomas with known clinical outcome. RESULTS
Sixty-eight patients with newly diagnosed breast carcinoma were included
in the current study. Sixty-five patients underwent FNAB (17 had
both FNAB and CBX) and 3 underwent CBX only. Extracted RNA was of
suitable quality for hybridization in 46 (71%) FNABs and 15 (75%)
CBXs. Total RNA yield in those samples was similar for single-pass
FNAB (mean = 3.6 μg and median = 2.2 μg; n = 46) and CBX (mean
= 2.8 μg and median = 2.0 μg; n = 15), with 1 μg or more of total
RNA in all cases. Transcriptional profiling was performed successfully
in all cases when it was attempted, in a total of 50 samples (38
FNABs and 12 CBXs), including matched FNAB and CBX samples from 10
patients. There were differences in gene expression profiles in 10
matched FNAB and CBX sample pairs. Genes that were expressed differently
in CBX samples, compared with FNAB samples, were recognized as being
predominantly from the endothelium, fibroblasts, myofibroblasts or
smooth muscle, and histiocytes. Corresponding microscopic cell counts
from FNABs demonstrated means of 80% tumor cells, 15% lymphocytes,
and 5% stromal cells, whereas CBXs contained 50% tumor cells, 20%
lymphocytes, and 30% stromal cells. Considering that CBXs are approximately
six-fold richer in nonlymphoid stromal cells than FNABs and that
CBXs differentially express a set of recognized stromal genes, the
authors used these biopsies to define a transcriptional profile of
breast carcinoma stroma. A set of 120 genes differentially expressed
in CBXs was assessed independently in a published breast carcinoma
genomic database to classify breast carcinomas based on stromal gene
expression. Subgroups of tumors with low or high stromal signal were
identified, but there was no correlation with the development of
systemic metastases within 5 years. CONCLUSIONS Both FNAB and CBX
yield a similar quality and quantity of total RNA and are suitable
for cDNA microarray analyses in approximately 70–75% of single-pass
samples. Transcriptional profiles from FNAB and CBX of the same tumor
generally are similar and are driven by the tumor cell population.
The authors concluded that each technique has relative advantages.
The FNABs provide transcriptional profiles that are a purer representation
of the tumor cell population, whereas transcriptional profiles from
CBXs include more repre sentation from nonlymphoid stromal elements.
Selection of the preferred needle biopsy sampling technique for genomic
studies of breast carcinomas should depend on whether variable stromal
gene expression is desirable in the samples. Cancer 2003;97:2960–71.
© 2003 American Cancer Society.DOI 10.1002/cncr.11435},
issn = {1097-0142},
keywords = {needle biopsy, comparison, microarray, transcriptional profiles},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.11435}
}
@ARTICLE{Symmans2005,
author = {Symmans, W F and Fiterman, D J and Anderson, S K and Ayers, M and
Rouzier, R and Dunmire, V and Stec, J and Valero, V and Sneige, N
and Albarracin, C and Wu, Y and Ross, J S and Wagner, P and Theriault,
R L and Arun, B and Kuerer, H and Hess, K R and Zhang, W and Hortobagyi,
G N and Pusztai, L},
title = {A single-gene biomarker identifies breast cancers associated with
immature cell type and short duration of prior breastfeeding},
journal = {Endocr. Relat. Cancer},
year = {2005},
volume = {12},
pages = {1059--1069},
number = {4},
month = dec,
abstract = {The pathogenesis of breast cancers that do not express estrogen receptors
or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood.
We had observed markedly elevated gene expression of gamma-aminobutyric
acid type A (GABAA) receptor subunit {pi} (GABA{pi}, GABRP) in some
breast cancers with ER-/HER2- phenotype. In this study, transcriptional
profiles (TxPs) were obtained from 82 primary invasive breast cancers
by oligonucleotide microarrays. Real-time reverse transcription-polymerase
chain reaction (RT-PCR) was used to measure GABA{pi} gene expression
in a separate cohort of 121 invasive breast cancers. GABA{pi} gene
expression values from TxP and RT-PCR were standardized and compared
with clinicopathologic characteristics in the 203 patients. GABA{pi}
gene expression was increased in 16% of breast cancers (13/82 TxP,
20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype
(60%), and breast cancers with basal-like genomic profile (60%).
The profile of genes coexpressed with GABA{pi} in these tumors was
consistent with an immature cell type. In multivariate linear regression
analysis, the level of GABA{pi} gene expression was associated with
ER-/HER2- phenotype (P<0.0001), younger age at diagnosis (P=0.0003),
and shorter lifetime duration of breastfeeding ([≤] 6 months)
in all women (P=0.017) and specifically in parous women (P=0.013).
GABA{pi} gene expression was also associated with combinations of
high grade with ER-/HER2- phenotype (P=0.002), and with Hispanic
ethnicity (P=0.036). GABA{pi} gene expression is increased in breast
cancers of immature (undifferentiated) cell type and is significantly
associated with shorter lifetime history of breastfeeding and with
high-grade breast cancer in Hispanic women.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/12/4/1059}
}
@ARTICLE{Synnergren2011,
author = {Synnergren, Jane and Ameen, Caroline and Lindahl, Anders and Olsson,
Bjorn and Sartipy, Peter},
title = {Expression of microRNAs and their target mRNAs in human stem cell-derived
cardiomyocyte clusters and in heart tissue},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {581-594},
number = {10},
abstract = {Recent studies have shown that microRNAs (miRNAs) act as posttranscriptional
regulators and that they play important roles during heart development
and in cardiac function. Thus, they may provide new means of altering
stem cell fate and differentiation processes. However, information
about the correlation between global miRNA and mRNA expression in
cardiomyocyte clusters (CMCs) derived from human embryonic stem cells
(hESC) and in fetal and adult heart tissue is lacking. In the present
study the global miRNA and mRNA expression in hESC-derived CMCs and
in fetal and adult heart tissue was investigated in parallel using
microarrays. Target genes for the differentially expressed miRNAs
were predicted using computational methods, and the concordance in
miRNA expression and mRNA levels of potential target genes was determined
across the experimental samples. The biology of the predicted target
genes was further explored regarding their molecular functions and
involvement in known regulatory pathways. A clear correlation between
the global miRNA expression and corresponding target mRNA expression
was observed. Using three different sources of cardiac tissue-like
samples, we defined the similarities between in vitro hESC-derived
CMCs and their in vivo counterparts. The results are in line with
previously reported observations that miRNAs repress mRNA expression
and additionally identify a number of novel miRNAs with potential
important roles in human cardiac tissue. The concordant miRNA expression
pattern observed among all the cardiac tissue-like samples analyzed
here provide a starting point for future ambitious studies aiming
towards assessment of the functional roles of specific miRNAs during
cardiomyocyte differentiation.},
doi = {10.1152/physiolgenomics.00074.2010},
eprint = {http://physiolgenomics.physiology.org/cgi/reprint/43/10/581.pdf},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/10/581}
}
@ARTICLE{Synnergren2007,
author = {Synnergren, Jane and Giesler, Theresa L. and Adak, Sudeshna and Tandon,
Reeti and Noaksson, Karin and Lindahl, Anders and Nilsson, Patric
and Nelson, Deirdre and Olsson, Björn and Englund, Mikael C.O. and
Abbot, Stewart and Sartipy, Peter},
title = {Differentiating Human Embryonic Stem Cells Express a Unique Housekeeping
Gene Signature},
journal = {STEM CELLS},
year = {2007},
volume = {25},
pages = {473--480},
number = {2},
abstract = {Abstract 10.1634/stemcells.2006-0247.abs Housekeeping genes (HKGs)
are involved in basic functions needed for the sustenance of the
cell and are assumed to be constitutively expressed at a constant
level. Based on these features, HKGs are frequently used for normalization
of gene expression data. In the present study, we used the CodeLink
Gene Expression Bioarray system to interrogate changes in gene expression
occurring during differentiation of human ESCs (hESCs). Notably,
in the three hESC lines used for the study, we observed that the
RNA levels of 56 frequently used HKGs varied to a degree that rendered
them inappropriate as reference genes. Therefore, we defined a novel
set of HKGs specifically for hESCs. Here we present a comprehensive
list of 292 genes that are stably expressed (coefficient of variation
<20%) in differentiating hESCs. These genes were further grouped
into high-, medium-, and low-expressed genes. The expression patterns
of these novel HKGs show very little overlap with results obtained
from somatic cells and tissues. We further explored the stability
of this novel set of HKGs in independent, publicly available gene
expression data from hESCs and observed substantial similarities
with our results. Gene expression was confirmed by real-time quantitative
polymerase chain reaction analysis. Taken together, these results
suggest that differentiating hESCs have a unique HKG signature and
underscore the necessity to validate the expression profiles of putative
HKGs. In addition, this novel set of HKGs can preferentially be used
as controls in gene expression analyses of differentiating hESCs.},
issn = {1549-4918},
keywords = {Gene expression, Microarray, In vitro differentiation, Human embryonic
stem cells, Housekeeping gene Normalization},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2006-0247}
}
@ARTICLE{Synnergren2008,
author = {Synnergren, Jane and Ã…kesson, Karolina and Dahlenborg, Kerstin and
Vidarsson, Hilmar and Améen, Caroline and Steel, Daniella and Lindahl,
Anders and Olsson, Björn and Sartipy, Peter},
title = {Molecular Signature of Cardiomyocyte Clusters Derived from Human
Embryonic Stem Cells},
journal = {STEM CELLS},
year = {2008},
volume = {26},
pages = {1831--1840},
number = {7},
abstract = {Abstract 10.1634/stemcells.2007-1033.abs Human embryonic stem cells
(hESCs) can differentiate in vitro into spontaneously contracting
cardiomyocytes (CMs). These cells may prove extremely useful for
various applications in basic research, drug discovery, and regenerative
medicine. To fully use the potential of the cells, they need to be
extensively characterized, and the regulatory mechanisms that control
hESC differentiation toward the cardiac lineage need to be better
defined. In this study, we used microarrays to analyze, for the first
time, the global gene expression profile of isolated hESC-derived
CM clusters. By comparing the clusters with undifferentiated hESCs
and using stringent selection criteria, we identified 530 upregulated
and 40 downregulated genes in the contracting clusters. To further
characterize the family of upregulated genes in the hESC-derived
CM clusters, the genes were classified according to their Gene Ontology
annotation. The results indicate that the hESC-derived CM clusters
display high similarities, on a molecular level, to human heart tissue.
Moreover, using the family of upregulated genes, we created protein
interaction maps that revealed topological characteristics. We also
searched for cellular pathways among the upregulated genes in the
hESC-derived CM clusters and identified eight significantly upregulated
pathways. Real-time quantitative polymerase chain reaction and immunohistochemical
analysis confirmed the expression of a subset of the genes identified
by the microarrays. Taken together, the results presented here provide
a molecular signature of hESC-derived CM clusters and further our
understanding of the biological processes that are active in these
cells. Disclosure of potential conflicts of interest is found at
the end of this article.},
issn = {1549-4918},
keywords = {Human embryonic stem cells, Differentiation, Cardiomyocytes, Gene
expression},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-1033}
}
@ARTICLE{Syre2009,
author = {Syre, H. and Myneedu, V. P. and Arora, V. K. and Grewal, H. M. S.},
title = {Direct Detection of Mycobacterial Species in Pulmonary Specimens
by Two Rapid Amplification Tests, the Gen-Probe Amplified Mycobacterium
tuberculosis Direct Test and the GenoType Mycobacteria Direct Test},
journal = {J. Clin. Microbiol.},
year = {2009},
volume = {47},
pages = {3635--3639},
number = {11},
month = nov,
abstract = {Nucleic acid amplification tests have improved tuberculosis diagnostics
considerably. This study evaluates a new amplification test, the
GenoType Mycobacteria Direct (GTMD) test, for detection of the Mycobacterium
tuberculosis complex, Mycobacterium avium, Mycobacterium intracellulare,
Mycobacterium kansasii, and Mycobacterium malmoense directly in 61
sputum samples. Thirty (49.2%) samples were auramine smear positive,
and 31 (50.8%) were smear negative. The GTMD results were compared
to the Gen-Probe Amplified M. tuberculosis Direct (MTD) test results,
using culturing and sequencing of the 16S rRNA gene as reference
methods. The GTMD test could identify 28 of 29 samples containing
the M. tuberculosis complex and was negative in a sputum sample containing
M. intracellulare. The overall sensitivity and specificity results
were 93.3% and 90.0% for the GTMD test, respectively, and 93.1% and
93.5% for the MTD test, respectively. The GTMD test is rapid and
can be easily included in routine clinical laboratories for the direct
detection of the M. tuberculosis complex in smear-positive sputum
samples as an adjunct to microscopy and culture. Further studies
are needed to evaluate the performance of the GTMD test for the detection
of atypical mycobacteria.},
url = {http://jcm.asm.org/cgi/content/abstract/47/11/3635}
}
@ARTICLE{Szuecs2010,
author = {Sz?cs, Attila and Jäger, Katalin and Jurca, Manuela E. and Fábián,
Attila and Bottka, Sándor and Zvara, Á?gnes and Barnabás, Beáta and
Fehér, Attila},
title = {Histological and microarray analysis of the direct effect of water
shortage alone or combined with heat on early grain development in
wheat (Triticum aestivum)},
journal = {Physiologia Plantarum},
year = {2010},
volume = {140},
pages = {174--188},
number = {2},
abstract = {Based on the in silico analysis of the representation of expressed
sequence tags (ESTs) in wheat grain-related cDNA libraries, a specific
15k oligonucleotide microarray has been developed in order to monitor
environmental stress-dependent gene expression changes in the wheat
caryopses. Using this array, the effect of water withdrawal, with
and without additional heat stress, has been investigated during
the first five days of kernel development on two wheat cultivars
differing in their drought sensitivity. Water shortage affected (more
than twofold change) the expression of only 0.5% of the investigated
genes. A parallel heat treatment increased the ratio of responding
genes to 5-7% because of the temperature stress and/or the increased
water deficit because of enhanced evaporation. It could be established
that the two cultivars, differing in their long-term adaptation capabilities
to drought, responded to the short and direct stress treatments on
the same way. In response to the combined drought and heat treatment,
the coordinately altered expression of genes coding for storage proteins,
enzymes involved in sugar/starch metabolism, histone proteins, heat
shock proteins, proteases, tonoplast aquaporins as well as several
transcription factors has been observed. These gene expression changes
were in agreement with histological data that demonstrated the accelerated
development of the embryo as well as the endosperm.},
issn = {1399-3054},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-3054.2010.01394.x}
}
@ARTICLE{Szabo2009,
author = {Szabo, David T. and Richardson, Vicki M. and Ross, David G. and Diliberto,
Janet J. and Kodavanti, Prasada R. S. and Birnbaum, Linda S.},
title = {Effects of Perinatal PBDE Exposure on Hepatic Phase I, Phase II,
Phase III, and Deiodinase 1 Gene Expression Involved in Thyroid Hormone
Metabolism in Male Rat Pups},
journal = {Toxicol. Sci.},
year = {2009},
volume = {107},
pages = {27--39},
number = {1},
month = jan,
abstract = {Previous studies demonstrated that perinatal exposure to polybrominated
diphenyl ethers (PBDEs), a major class of brominated flame retardants,
may affect thyroid hormone (TH) concentrations by inducing hepatic
uridinediphosphate-glucoronosyltransferases (UGTs). This study further
examines effects of the commercial penta mixture, DE-71, on genes
related to TH metabolism at different developmental time points in
male rats. DE-71 is predominately composed of PBDE congeners 47,
99, 100, 153, 154 with low levels of brominated dioxin and dibenzofuran
contaminants. Pregnant Long-Evans rats were orally administered 1.7
(low), 10.2 (mid), or 30.6 (high) mg/kg/day of DE-71 in corn oil
from gestational day (GD) 6 to postnatal day (PND) 21. Serum and
liver were collected from male pups at PND 4, 21, and 60. Total serum
thyroxine (T4) decreased to 57% (mid) and 51% (high) on PND 4, and
46% (mid) dose and 25% (high) on PND 21. Cyp1a1, Cyp2b1/2, and Cyp3a1
enzyme and mRNA expression, regulated by aryl hydrocarbon receptor,
constitutive androstane receptor, and pregnane xenobiotic receptor,
respectively, increased in a dose-dependent manner. UGT-T4 enzymatic
activity significantly increased, whereas age and dose-dependent
effects were observed for Ugt1a6, 1a7, and 2b mRNA. Sult1b1 mRNA
expression increased, whereas that of transthyretin (Ttr) decreased
as did both the deiodinase I (D1) enzyme activity and mRNA expression.
Hepatic efflux transporters Mdr1 (multidrug resistance), Mrp2 (multidrug
resistance-associated protein), and Mrp3 and influx transporter Oatp1a4
mRNA expression increased. In this study the most sensitive responses
to PBDEs following DE-71 exposure were CYP2B and D1 activities and
Cyb2b1/2, d1, Mdr1, Mrp2, and Mrp3 gene expression. All responses
were reversible by PND 60. In conclusion, deiodination, active transport,
and sulfation, in addition to glucuronidation, may be involved in
disruption of TH homeostasis due to perinatal exposure to DE-71 in
male rat offspring.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/107/1/27}
}
@ARTICLE{Szabo2010,
author = {Szabo, Eva and Rampalli, Shravanti and Risueno, Ruth M. and Schnerch,
Angelique and Mitchell, Ryan and Fiebig-Comyn, Aline and Levadoux-Martin,
Marilyne and Bhatia, Mickie},
title = {Direct conversion of human fibroblasts to multilineage blood progenitors},
journal = {Nature},
year = {2010},
volume = {468},
pages = {521--526},
number = {7323},
month = nov,
comment = {10.1038/nature09591},
issn = {0028-0836},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nature09591}
}
@ARTICLE{Szabo-Fresnais2010,
author = {Szabo-Fresnais, Nicolas and Lefebvre, Florence and Germain, Aurore
and Fischmeister, Rodolphe and Pomérance, Martine},
title = {A new regulation of IL-6 production in adult cardiomyocytes by [beta]-adrenergic
and IL-1[beta] receptors and induction of cellular hypertrophy by
IL-6 trans-signalling},
journal = {Cellular Signalling},
year = {2010},
volume = {22},
pages = {1143--1152},
number = {7},
month = jul,
abstract = {The sympathetic nervous system and pro-inflammatory cytokines play
key roles in numerous cardiovascular disorders. Chronic [beta]-adrenergic
receptor ([beta]-AR) stimulation in myocardium induces expression
of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and interleukin-6
(IL-6), which contribute to cardiac hypertrophy and failure. To evaluate
the relationship between [beta]-AR stimulation and pro-inflammatory
cytokines, we studied the effects of the [beta]-AR agonist isoprenaline
(ISO) on IL-1-induced IL-6 production in adult rat ventricular myocytes
(ARVMs). We report that ISO and IL-1 synergistically enhanced IL-6
gene expression and secretion. The synergistic effect of ISO was
mimicked by cAMP elevating agents and involved the Gs protein/cAMP/PKA
signalling pathway, but not the exchange factor EPAC. To evaluate
the contribution of IL-6 to cellular hypertrophy, we examined the
signalling pathways stimulated by the membrane-bound IL-6 receptor
(IL-6R), and the IL-6 soluble receptor (sIL-6R) involved in the mechanism
named IL-6 trans-signalling. The IL-6/sIL-6R complex promoted a rapid
and persistent phosphorylation of STAT3Tyr705 in ARVMs. Moreover,
IL-6 trans-signalling increased protein synthesis, c-fos gene expression
and B-type natriuretic peptide secretion, three markers of cardiac
hypertrophy. IL-6 trans-signalling also increased cell size. In contrast,
IL-6 alone had no significant effect on either cell size or STAT3
phosphorylation although it induced phosphorylation of ERK1/2, AKT
and S6K, demonstrating the presence of a functional IL-6R in ARVMs.
Taken together, these results demonstrate that [beta]-AR stimulation
synergises with IL-1 for IL-6 secretion in adult ventricular myocytes
and indicate that IL-6 induces cardiac hypertrophy only via IL-6
trans-signalling. The IL-6 soluble receptor may thus serve as a switch
for IL-6 to activate STAT3 phosphorylation and hypertrophy.},
issn = {0898-6568},
keywords = {[beta]-Adrenergic receptors, cAMP, IL-6, IL-1, STAT3, Cardiac hypertrophy},
url = {http://www.sciencedirect.com/science/article/B6T2M-4YK7J49-2/2/5abb6e11c8c13f171e7ffa87a6242c19}
}
@ARTICLE{SzabA³2011,
author = {Szabó, Pavol and Kolář, Michal and Dvořánková, Barbora and
Lacina, Lukáš and Å tork, Jiřà and VlÄ?ek, ÄŒestmÃr and Strnad,
Hynek and Tvrdek, Miroslav and Smetana, Karel},
title = {Mouse 3T3 fibroblasts under the influence of fibroblasts isolated
from stroma of human basal cell carcinoma acquire properties of multipotent
stem cells},
journal = {Biology of the Cell},
year = {2011},
volume = {103},
pages = {233--248},
number = {5},
abstract = {Background information. Multipotent mesenchymal stem cells can participate
in the formation of a microenvironment stimulating the aggressive
behaviour of cancer cells. Moreover, cells exhibiting pluripotent
ESC (embryonic stem cell) markers (Nanog and Oct4) have been observed
in many tumours. Here, we investigate the role of cancer-associated
fibroblasts in the formation of stem cell supporting properties of
tumour stroma. We test the influence of fibroblasts isolated from
basal cell carcinoma on mouse 3T3 fibroblasts, focusing on the expression
of stem cell markers and plasticity in vitro by means of microarrays,
qRT-PCR (quantitative real-time PCR) and immunohistochemistry.Results.
We demonstrate the biological activity of the cancer stromal fibroblasts
by influencing the 3T3 fibroblasts to express markers such as Oct4,
Nanog and Sox2 and to show differentiation potential similar to mesenchymal
stem cells. The role of growth factors such as IGF2 (insulin-like
growth factor 2), FGF7 (fibroblast growth factor 7), LEP (leptin),
NGF (nerve growth factor) and TGFβ (transforming growth factor β),
produced by the stromal fibroblasts, is established to participate
in their bioactivity. Uninduced 3T3 do not express the stem cell
markers and show minimal differentiation potential.Conclusions. Our
observations indicate the pro-stem cell activity of cancer-associated
fibroblasts and underline the role of epithelial—mesenchymal interaction
in tumour biology.},
doi = {10.1042/BC20100113},
issn = {1768-322X},
keywords = {basal cell carcinoma (BCC), keratinocyte, stem cell plasticity, stem
cell, tumour stroma},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1042/BC20100113}
}
@ARTICLE{Szafranska2008,
author = {Szafranska, Anna E. and Davison, Timothy S. and Shingara, Jaclyn
and Doleshal, Martina and Riggenbach, Judith A. and Morrison, Carl
D. and Jewell, Scott and Labourier, Emmanuel},
title = {Accurate Molecular Characterization of Formalin-Fixed, Paraffin-Embedded
Tissues by microRNA Expression Profiling},
journal = {J. Mol. Diagn.},
year = {2008},
volume = {10},
pages = {415--423},
number = {5},
month = sep,
abstract = {Formalin-fixed, paraffin-embedded tissues are an invaluable tool for
biomarker discovery and validation. As these archived specimens are
not always compatible with modern genomic techniques such as gene
expression arrays, we assessed the use of microRNA (miRNA) as an
alternative means for the reliable molecular characterization of
formalin-fixed, paraffin-embedded tissues. Expression profiling using
two different microarray platforms and multiple mouse and human formalin-fixed,
paraffin-embedded tissue types resulted in the correlation ratios
of miRNA expression levels between frozen and fixed tissue pairs
ranging from 0.82 to 0.99, depending on the cellular heterogeneity
of the tissue type. The same miRNAs were identified as differentially
expressed between tissues using both fixed and frozen specimens.
While formalin fixation time had only marginal effects on microarray
performance, extended storage times for tissue blocks (up to 11 years)
resulted in a gradual loss of detection of miRNAs expressed at low
levels. Method reproducibility and accuracy were also evaluated in
two different tissues stored for different lengths of time. The technical
variation between full process replicates, including independent
RNA isolation methods, was approximately 5%, and the correlation
of expression levels between microarray and real-time quantitative
reverse transcriptase polymerase chain reaction was 0.98. Together,
these data demonstrate that miRNA expression profiling is an accurate
and robust method for the molecular analysis of archived clinical
specimens, potentially extending the use of miRNAs as new diagnostic,
prognostic, and treatment response biomarkers.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/10/5/415}
}
@ARTICLE{Szafranska2008a,
author = {Szafranska, Anna E. and Doleshal, Martina and Edmunds, Hayward S.
and Gordon, Stuart and Luttges, Jutta and Munding, Johanna B. and
Barth, Richard J., Jr and Gutmann, Edward J. and Suriawinata, Arief
A. and Marc Pipas, J. and Tannapfel, Andrea and Korc, Murray and
Hahn, Stephan A. and Labourier, Emmanuel and Tsongalis, Gregory J.},
title = {Analysis of MicroRNAs in Pancreatic Fine-Needle Aspirates Can Classify
Benign and Malignant Tissues},
journal = {Clin. Chem.},
year = {2008},
volume = {54},
pages = {1716--1724},
number = {10},
month = oct,
abstract = {Background: MicroRNAs (miRNAs) are RNA molecules that are involved
in the regulation of many cellular processes, including those related
to human cancers. The aim of this study was to determine, as a proof
of principle, whether specific candidate miRNAs could be detected
in fine-needle aspirate (FNA) biopsies of pancreatic ductal adenocarcinoma
(PDAC) and could accurately differentiate malignant from benign pancreatic
tissues. Methods: We used TaqMan(R) assays to quantify miRNA levels
in FNA samples collected in RNARetain (n = 16) and compared the results
with a training set consisting of frozen macrodissected pancreatic
samples (n = 20). Results: Quantitative reverse-transcription PCR
analysis confirmed that miRNA levels are affected in PDAC FNAs and
correlate well with the changes observed in the training set of frozen
pancreatic samples. Analysis of the amounts produced for a few specific
miRNAs enabled identification of PDAC samples. The combination of
miR-196a and miR-217 biomarkers further improved the ability to distinguish
between healthy tissue, PDAC, and chronic pancreatitis in the training
set (P = 8.2 x 10-10), as well as segregate PDAC FNA samples from
other FNA samples (P = 1.1 x 10-5). Furthermore, we showed that miR-196a
production is likely specific to PDAC cells and that its incidence
paralleled the progression of PDAC. Conclusions: To the best of our
knowledge, this study is the first to evaluate the diagnostic potential
of miRNAs in a clinical setting and has shown that miRNA analysis
of pancreatic FNA biopsy samples can aid in the pathologic evaluation
of suspicious cases and may provide a new strategy for improving
the diagnosis of pancreatic diseases.},
url = {http://www.clinchem.org/cgi/content/abstract/54/10/1716}
}
@ARTICLE{Szakasits2009,
author = {Szakasits, Dagmar and Heinen, Petra and Wieczorek, Krzysztof and
Hofmann, Julia and Wagner, Florian and Kreil, David P. and Sykacek,
Peter and Grundler, Florian M. W. and Bohlmann, Holger},
title = {The transcriptome of syncytia induced by the cyst nematode Heterodera
schachtii in Arabidopsis roots},
journal = {The Plant Journal},
year = {2009},
volume = {57},
pages = {771--784},
number = {5},
abstract = {Summary Arabidopsis thaliana is a host for the sugar beet cyst nematode
Heterodera schachtii. Juvenile nematodes invade the roots and induce
the development of a syncytium, which functions as a feeding site
for the nematode. Here, we report on the transcriptome of syncytia
induced in the roots of Arabidopsis. Microaspiration was employed
to harvest pure syncytium material, which was then used to prepare
RNA for hybridization to Affymetrix GeneChips. Initial data analysis
showed that the gene expression in syncytia at 5 and 15Â days post-infection
did not differ greatly, and so both time points were compared together
with control roots. Out of a total of 21Â 138 genes, 18.4% (3893)
had a higher expression level and 15.8% (3338) had a lower expression
level in syncytia, as compared with control roots, using a multiple-testing
corrected false discovery rate of below 5%. A gene ontology (GO)
analysis of up- and downregulated genes showed that categories related
to high metabolic activity were preferentially upregulated. A principal
component analysis was applied to compare the transcriptome of syncytia
with the transcriptome of different Arabidopsis organs (obtained
by the AtGenExpress project), and with specific root tissues. This
analysis revealed that syncytia are transcriptionally clearly different
from roots (and all other organs), as well as from other root tissues.},
issn = {1365-313X},
keywords = {Arabidopsis, plant pathogen, Heterodera schachtii, syncytium, transcriptome,
Affymetrix GeneChip},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2008.03727.x}
}
@ARTICLE{Szakacs2004,
author = {Szakács, Gergely and Annereau, Jean-Philippe and Lababidi, Samir
and Shankavaram, Uma and Arciello, Angela and Bussey, Kimberly J.
and Reinhold, William and Guo, Yanping and Kruh, Gary D. and Reimers,
Mark and Weinstein, John N. and Gottesman, Michael M.},
title = {Predicting drug sensitivity and resistance: Profiling ABC transporter
genes in cancer cells},
journal = {Cancer Cell},
year = {2004},
volume = {6},
pages = {129--137},
number = {2},
month = aug,
abstract = {For analysis of multidrug resistance, a major barrier to effective
cancer chemotherapy, we profiled mRNA expression of the 48 known
human ABC transporters in 60 diverse cancer cell lines (the NCI-60)
used by the National Cancer Institute to screen for anticancer activity.
The use of real-time RT-PCR avoided artifacts commonly encountered
with microarray technologies. By correlating the results with the
growth inhibitory profiles of 1,429 candidate anticancer drugs tested
against the cells, we identified which transporters are more likely
than others to confer resistance to which agents. Unexpectedly, we
also found and validated compounds whose activity is potentiated,
rather than antagonized, by the MDR1 multidrug transporter. Such
compounds may serve as leads for development.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-4D4KPHG-7/2/9b534289b74fe060c397a688478a642b}
}
@ARTICLE{Szalowska2011a,
author = {Szalowska, Ewa and Dijkstra, Martijn and Elferink, Marieke and Weening,
Desiree and de Vries, Marcel and Bruinenberg, Marcel and Hoek, Annemieke
and Roelofsen, Han and Groothuis, Geny and Vonk, Roel},
title = {Comparative analysis of the human hepatic and adipose tissue transcriptomes
during LPS-induced inflammation leads to the identification of differential
biological pathways and candidate biomarkers},
journal = {BMC Medical Genomics},
year = {2011},
volume = {4},
pages = {71},
number = {1},
abstract = {BACKGROUND:Insulin resistance (IR) is accompanied by chronic low grade
systemic inflammation, obesity, and deregulation of total body energy
homeostasis. We induced inflammation in adipose and liver tissues
in vitro in order to mimic inflammation in vivo with the aim to identify
tissue-specific processes implicated in IR and to find biomarkers
indicative for tissue-specific IR.METHODS:Human adipose and liver
tissues were cultured in the absence or presence of LPS and DNA Microarray
Technology was applied for their transcriptome analysis. Gene Ontology
(GO), gene functional analysis, and prediction of genes encoding
for secretome were performed using publicly available bioinformatics
tools (DAVID, STRING, SecretomeP). The transcriptome data were validated
by proteomics analysis of the inflamed adipose tissue secretome.RESULTS:LPS
treatment significantly affected 667 and 483 genes in adipose and
liver tissues respectively. The GO analysis revealed that during
inflammation adipose tissue, compared to liver tissue, had more significantly
upregulated genes, GO terms, and functional clusters related to inflammation
and angiogenesis. The secretome prediction led to identification
of 399 and 236 genes in adipose and liver tissue respectively. The
secretomes of both tissues shared 66 genes and the remaining genes
were the differential candidate biomarkers indicative for inflamed
adipose or liver tissue. The transcriptome data of the inflamed adipose
tissue secretome showed excellent correlation with the proteomics
data.CONCLUSIONS:The higher number of altered proinflammatory genes,
GO processes, and genes encoding for secretome during inflammation
in adipose tissue compared to liver tissue, suggests that adipose
tissue is the major organ contributing to the development of systemic
inflammation observed in IR. The identified tissue-specific functional
clusters and biomarkers might be used in a strategy for the development
of tissue-targeted treatment of insulin resistance in patients.},
doi = {10.1186/1755-8794-4-71},
issn = {1755-8794},
pubmedid = {21978410},
url = {http://www.biomedcentral.com/1755-8794/4/71}
}
@ARTICLE{Szalowska2011,
author = {Szalowska, Ewa and Meijer, Kees and Kloosterhuis, Niels and Razaee,
Farhad and Priebe, Marion and Vonk, Roel J.},
title = {Sub-chronic administration of stable GIP analog in mice decreases
serum LPL activity and body weight},
journal = {Peptides},
year = {2011},
volume = {32},
pages = {938--945},
number = {5},
month = may,
abstract = {GIP receptor knockout mice were shown to be protected from the development
of obesity on a high fat diet, suggesting a role of GIP in the development
of obesity. In our study we aimed to test the hypothesis if excess
of GIP could accelerate development of obesity and to identify GIP
gene targets in adipose tissue. Therefore, mice were kept on a chow
or a high fat diet and during the last 2 weeks D-Ala2-GIP or PBS
injections were performed. Afterwards, serum LPL activity and several
biochemical parameters (TG, FFA, cholesterol, glucose, insulin, resistin,
IL-6, IL-1[beta], TNF[alpha], GIP) were measured. Fat tissue was
isolated and QPCR was performed for a set of genes involved in energy
metabolism and inflammation. A DNA-microarray was used to identify
GIP gene targets in adipose tissue of the chow diet group. We found
that the D-Ala2-GIP injections caused a significant decrease in both
body weight and LPL activity compared to controls. Serum biochemical
parameters were not affected by D-Ala2-GIP, with an exception for
resistin and insulin. The set of inflammatory genes were significantly
decreased in adipose tissue in the D-Ala2-GIP injected animals on
a chow diet. A DNA-microarray revealed that APO-genes and CYP-genes
were affected by D-Ala2-GIP treatment in adipose tissue. These results
suggest that the body weight-reducing effect of D-Ala2-GIP may be
explained by lower LPL activity and insulin serum level. Moreover,
the identified GIP candidate gene targets in adipose tissue link
GIP action to lipid metabolism exerted by APO and CYP genes.},
issn = {0196-9781},
keywords = {GIP, Insulin resistance, Type 2 diabetes, Adipose tissue, Lipid metabolism},
url = {http://www.sciencedirect.com/science/article/pii/S0196978111000805}
}
@ARTICLE{Szaniszlo2009,
author = {Szaniszlo, Peter and German, Peter and Hajas, Gyorgy and Saenz, David
N. and Woodberry, Mitchell W. and Kruzel, Marian L. and Boldogh,
Istvan},
title = {Effects of Colostrinin(TM) on gene expression-transcriptomal network
analysis},
journal = {International Immunopharmacology},
year = {2009},
volume = {9},
pages = {181--193},
number = {2},
month = feb,
abstract = {Colostrinin(TM) (CLN) is a uniform mixture of low-molecular weight
proline-rich polypeptides isolated from the mother's first milk,
colostrum. Exposure of cells to CLN decreases intracellular levels
of reactive oxygen species by regulating glutathione metabolism and
modulating activities of antioxidant enzymes and mitochondrial function.
It also inhibits beta amyloid-induced apoptosis and induces neurite
outgrowth of pheochromocytoma cells. Administration of CLN to Alzheimer's
disease patients has resulted in a stabilizing effect on cognitive
function. We analyzed CLN-induced gene expression changes using high-density
oligonucleotide arrays and transcriptomal network analysis. We found
that CLN elicited highly complex and multiphasic changes in the gene
expression profile of treated cells. CLN treatment affected a total
of 58 molecular networks, 27 of which contained at least 10 differentially
expressed genes. Here we present CLN-modulated gene networks as potential
underlying molecular mechanisms leading to the reported effects of
CLN on cellular oxidative state, chemokine and cytokine production,
and cell differentiation, as well as on pathological processes like
allergy, asthma, Alzheimer's, and other neurological diseases. Based
on our results, we also predict possible modulatory effects of CLN
on adipocytokine gene networks that play a crucial role in the pathobiology
of diabetes, cardiovascular disorders, obesity, and inflammation.
Taken together, CLN-altered gene expression networks presented here
provide the molecular basis for previously described biological phenomena
and predict potential fields of application for CLN in the prevention
and treatment of diseases.},
issn = {1567-5769},
keywords = {Colostrinin, Microarray, Transcriptomal network analysis},
url = {http://www.sciencedirect.com/science/article/B6W7N-4TY3WV7-3/2/42bb04851a8e634ddcd14b9aae2b9cce}
}
@ARTICLE{Szauter2010,
author = {Szauter, K.M. and Ordas, A. and Laxer, R.M. and Pope, E. and Wherrett,
D. and Alman, B. and Mink, M. and Boyd, C.D. and Csiszar, K. and
Hinek, A.},
title = {A novel fibrotic disorder associated with increased dermal fibroblast
proliferation and downregulation of genes of the microfibrillar network},
journal = {British Journal of Dermatology},
year = {2010},
volume = {163},
pages = {1102--1115},
number = {5},
abstract = {Summary Clinical evaluation of a young woman with subcutaneous fibrotic
nodules, progressive distal joint contractures and marfanoid stature
revealed a previously unrecognized fibrotic disorder characterized
by several unique phenotypic features and some features overlapping
with known disorders. Mutational analysis of the FBN1 and FBN2 genes
excluded Marfan syndrome and congenital contractural arachnodactyly.
MMP2 gene sequence analysis excluded multicentric osteolysis, nodulosis
and arthropathy. The lack of mutations within the MAGP2 gene also
excluded an MAGP2-associated disorder. In order to establish the
mechanistic basis for the severe skin pathology noted in this patient,
we performed transcriptional profiling of dermal fibroblasts, and
candidate gene expression studies in conjunction with immunocytochemistry
and cell-based and functional assays. Data from these experiments
have further excluded any previously recognized fibrotic disorder
and identified a unique pattern of gene expression in this patient
consistent with progressive fibrosis. The pathogenic mechanisms included
persistent proliferation of dermal fibroblasts in coexistence with
a disarray of the microfibrillar network. Collagen accumulation,
moreover, could be linked to extensive crosslinking resulting from
increased activities of lysyl oxidases (LOX and LOXL), and lack of
remodelling due to deficiencies in collagenolytic matrix metalloproteinases.
The disorder may represent a novel syndrome in which transforming
growth factor-β1-independent dermal fibrosis, unlike known microfibrillar
disorders caused by single gene deficiencies, associates with a disarray
of the microfibrillar network.},
issn = {1365-2133},
keywords = {fibrosis, LOX, LOXL, microfibrillar, scleroderma, transforming growth
factor-β},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2133.2010.09911.x}
}
@ARTICLE{Sze2004,
author = {Sze, Heven and Padmanaban, Senthilkumar and Cellier, Francoise and
Honys, David and Cheng, Ning-Hui and Bock, Kevin W. and Conejero,
Genevieve and Li, Xiyan and Twell, David and Ward, John M. and Hirschi,
Kendal D.},
title = {Expression Patterns of a Novel AtCHX Gene Family Highlight Potential
Roles in Osmotic Adjustment and K+ Homeostasis in Pollen Development},
journal = {Plant Physiology},
year = {2004},
volume = {136},
pages = {2532--2547},
number = {1},
month = sep,
abstract = {A combined bioinformatic and experimental approach is being used to
uncover the functions of a novel family of cation/H+ exchanger (CHX)
genes in plants using Arabidopsis as a model. The predicted protein
(85-95 kD) of 28 AtCHX genes after revision consists of an amino-terminal
domain with 10 to 12 transmembrane spans (approximately 440 residues)
and a hydrophilic domain of approximately 360 residues at the carboxyl
end, which is proposed to have regulatory roles. The hydrophobic,
but not the hydrophilic, domain of plant CHX is remarkably similar
to monovalent cation/proton antiporter-2 (CPA2) proteins, especially
yeast (Saccharomyces cerevisiae) KHA1 and Synechocystis NhaS4. Reports
of characterized fungal and prokaryotic CPA2 indicate that they have
various transport modes, including K+/H+ (KHA1), Na+/H+-K+ (GerN)
antiport, and ligand-gated ion channel (KefC). The expression pattern
of AtCHX genes was determined by reverse transcription PCR, promoter-driven{beta}
-glucuronidase expression in transgenic plants, and Affymetrix ATH1
genome arrays. Results show that 18 genes are specifically or preferentially
expressed in the male gametophyte, and six genes are highly expressed
in sporophytic tissues. Microarray data revealed that several AtCHX
genes were developmentally regulated during microgametogenesis. An
exciting idea is that CHX proteins allow osmotic adjustment and K+
homeostasis as mature pollen desiccates and then rehydrates at germination.
The multiplicity of CHX-like genes is conserved in higher plants
but is not found in animals. Only 17 genes, OsCHX01 to OsCHX17, were
identified in rice (Oryza sativa) subsp. japonica, suggesting diversification
of CHX in Arabidopsis. These results reveal a novel CHX gene family
in flowering plants with potential functions in pollen development,
germination, and tube growth.},
url = {http://www.plantphysiol.org/cgi/content/abstract/136/1/2532}
}
@ARTICLE{Szewczuk2010,
author = {Szewczuk, Elektra and Thapa, Kiran and Anninos, Terry and McPhie,
Kenneth and Higgins, Geoff and Dwyer, Dominic and Stanley, Keith
and Iredell, Jonathan},
title = {Rapid semi-automated quantitative multiplex tandem PCR (MT-PCR) assays
for the differential diagnosis of influenza-like illness},
journal = {BMC Infectious Diseases},
year = {2010},
volume = {10},
pages = {113},
number = {1},
abstract = {BACKGROUND:Influenza A, including avian influenza, is a major public
health threat in developed and developing countries. Rapid and accurate
detection is a key component of strategies to contain spread of infection,
and the efficient diagnosis of influenza-like-illness is essential
to protect health infrastructure in the event of a major influenza
outbreak.METHODS:We developed a multiplexed PCR (MT-PCR) assay for
the simultaneous diagnosis of respiratory viruses causing influenza-like
illness, including the specific recognition of influenza A haemagglutinin
subtypes H1, H3, and H5. We tested several hundred clinical specimens
in two diagnostic reference laboratories and compared the results
with standard techniques.RESULTS:The sensitivity and specificity
of these assays was higher than individual assays based on direct
antigen detection and standard PCR against a range of control templates
and in several hundred clinical specimens. The MT-PCR assays provided
differential diagnoses as well as potentially useful quantitation
of virus in clinical samples.CONCLUSIONS:MT-PCR is a potentially
powerful tool for the differential diagnosis of influenza-like illness
in the clinical diagnostic laboratory.},
doi = {10.1186/1471-2334-10-113},
issn = {1471-2334},
pubmedid = {20459845},
url = {http://www.biomedcentral.com/1471-2334/10/113}
}
@ARTICLE{Szodoray2006,
author = {Szodoray, P. and Alex, P. and Frank, M. B. and Turner, M. and Turner,
S. and Knowlton, N. and Cadwell, C. and Dozmorov, I. and Tang, Y.
and Wilson, P. C. and Jonsson, R. and Centola, M.},
title = {A genome-scale assessment of peripheral blood B-cell molecular homeostasis
in patients with rheumatoid arthritis},
journal = {Rheumatology},
year = {2006},
volume = {45},
pages = {1466--1476},
number = {12},
month = dec,
abstract = {Objective. While rheumatoid arthritis (RA) is considered a prototypical
autoimmune disease, the specific roles of B-cells in RA pathogenesis
is not fully delineated. Methods. We performed microarray expression
profiling of peripheral blood B-cells from RA patients and controls.
Data were analysed using differential gene expression analysis and
gene networking' analysis (characterizing clusters of functionally
inter-relelated genes) to identify both regulatory genes and the
pathways in which they participate. Results were confirmed by quantitative
real-time polymerase chain reaction and by measuring the levels of
10 serum cytokines involved in the pathways identified. Results.
Genes regulating and effecting the cell-cycle, proliferation, apoptosis,
autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation
were differentially expressed in RA B-cells. Moreover, the serum
levels of several soluble factors that modulate these pathways, including
IL-1{beta}, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly
increased in this cohort of RA patients. Conclusions. These results
outline aspects of the multifaceted role B-cells play in RA pathogenesis
in which immune dysregulation in RA modulates B-cell biology and
thereby contributes to the induction and perpetuation of a pathogenic
humoral immune response.},
url = {http://rheumatology.oxfordjournals.org/cgi/content/abstract/45/12/1466}
}
@ARTICLE{Sztajer2008,
author = {Sztajer, Helena and Lemme, Andre and Vilchez, Ramiro and Schulz,
Stefan and Geffers, Robert and Yip, Cindy Ying Yin and Levesque,
Celine M. and Cvitkovitch, Dennis G. and Wagner-Dobler, Irene},
title = {Autoinducer-2-Regulated Genes in Streptococcus mutans UA159 and Global
Metabolic Effect of the luxS Mutation},
journal = {J. Bacteriol.},
year = {2008},
volume = {190},
pages = {401--415},
number = {1},
month = jan,
abstract = {Autoinducer 2 (AI-2) is the only species-nonspecific autoinducer known
in bacteria and is produced by both gram-negative and gram-positive
organisms. Consequently, it is proposed to function as a universal
quorum-sensing signal for interaction between bacterial species.
AI-2 is produced as the by-product of a metabolic transformation
carried out by the LuxS enzyme. To separate the metabolic function
of the LuxS enzyme from the signaling role of AI-2, we carried out
a global transcriptome analysis of a luxS null mutant culture of
Streptococcus mutans UA159, an important cariogenic bacterium and
a crucial component of the dental plaque biofilm community, in comparison
to a luxS null mutant culture supplemented with chemically pure 4,5-dihydroxy-2,3-pentanedione,
the precursor of AI-2. The data revealed fundamental changes in gene
expression affecting 585 genes (30% of the genome) which could not
be restored by the signal molecule AI-2 and are therefore not caused
by quorum sensing but by lack of the transformation carried out by
the LuxS enzyme in the activated methyl cycle. All functional classes
of enzymes were affected, including genes known to be important for
biofilm formation, bacteriocin synthesis, competence, and acid tolerance.
At the same time, 59 genes were identified whose transcription clearly
responded to the addition of AI-2. Some of them were related to protein
synthesis, stress, and cell division. Three membrane transport proteins
were upregulated which are not related to any of the known AI-2 transporters.
Three transcription factors were identified whose transcription was
stimulated repeatedly by AI-2 addition during growth. Finally, a
global regulatory protein, the {delta} subunit of the RNA polymerase
(rpoE), was induced 147-fold by AI-2, representing the largest differential
gene expression observed. The data show that many phenotypes related
to the luxS mutation cannot be ascribed to quorum sensing and have
identified for the first time regulatory proteins potentially mediating
AI-2-based signaling in gram-positive bacteria.},
url = {http://jb.asm.org/cgi/content/abstract/190/1/401}
}
@ARTICLE{Szuchet2011,
author = {Szuchet, Sara and Nielsen, Joseph A. and Lovas, Gabor and Domowicz,
Miriam S. and de Velasco, Javier M. and Maric, Dragan and Hudson,
Lynn D.},
title = {The genetic signature of perineuronal oligodendrocytes reveals their
unique phenotype},
journal = {European Journal of Neuroscience},
year = {2011},
volume = {34},
pages = {1906--1922},
number = {12},
abstract = {Oligodendrocytes – best known for assembling central nervous system
myelin – can be categorized as precursors, myelin-forming cells
and non-myelinating perineuronal cells. Perineuronal oligodendrocytes
have been well characterized morphologically and ultrastructurally,
but knowledge about their function remains scanty. It has been proposed
that perineuronal oligodendrocytes support neurons and, following
injury, transform into myelin-synthesizing cells. Recent findings
implicating perineuronal oligodendrocytes in cytoarchitectural abnormalities
in the prefrontal cortex of schizophrenia and other psychiatric disorders
shed new light on these cells. We have obtained the genetic signature
of perineuronal oligodendrocytes by identifying gene expression differences
between oligodendrocyte subpopulations using cell-specific tags,
microarray technology, quantitative time-resolved polymerase chain
reaction and bioinformatics tools. We show that perineuronal cells
are the progeny of oligodendrocyte progenitors and, hence, are members
of the oligodendrocyte lineage. Physiologically they exhibit a novel
phenotype. Their expression of PDGFR-αβ and its growth factor ligand
PDGF-CC sets them apart from members of their lineage as this receptor
precludes their response to the same growth factors that act on myelinating
cells. Their coordinate expression and context-specific usage of
transcription factors Olig2, Ascl1 and Pax6, together with the prominent
presence of transcription factors Pea3, Lhx2 and Otx2 – not hitherto
linked to the oligodendrocyte lineage – suggested a cell with features
that blur the boundary between a neuron and a glial cell. But they
also maintain a reservoir of untranslated transcripts encoding major
myelin proteins presumably for a demyelinating episode. This first
molecular characterization of perineuronal oligodendrocytes revealed
the striking difference between the myelinating and non-myelinating
phenotypes.},
doi = {10.1111/j.1460-9568.2011.07922.x},
issn = {1460-9568},
keywords = {cell fate specification, glial cells, oligodendrocyte–neuron interaction,
rat, remyelination, signaling, transcription factors},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2011.07922.x}
}
@ARTICLE{Szyszko2006,
author = {Szyszko, E. and Brokstad, K. and Cox, R. J. and Hovden, A.-O. and
Madhun, A. and Haaheim, L. R.},
title = {Impact of Influenza Vaccine Formulation with a Detailed Analysis
of the Cytokine Response},
journal = {Scandinavian Journal of Immunology},
year = {2006},
volume = {64},
pages = {467--475},
number = {5},
abstract = {Abstract Vaccination provides the most effective method of limiting
the impact of influenza. Inactivated influenza vaccines are available
in three formulations and more information needs to be generated
on how antigen presented in different vaccine formulations influences
the subsequent immune response. In the present study, we have investigated
the effect of two different influenza vaccine formulations on the
resulting antibody and cytokine responses and compared these responses
with influenza infection. Mice were vaccinated intramuscularly with
one or two doses of whole or split virus vaccine or alternatively
intranasally infected with influenza virus. Lymphocytes were isolated
from spleen cells and stimulated in vitro for 24 or 72Â h for analysis
of cytokine profile at the gene expression and at the protein level.
Additionally, whole blood was collected and the serum antibody response
investigated by haemagglutination inhibition (HI) and enzyme-linked
immunosorbent assay (ELISA). We found that one dose of whole virus
vaccine induced higher antibody and cytokine responses and thus was
more immunogenic in unprimed mice than split virus vaccine. Whole
virus vaccine induced a strong IFN-γ (type 1) immune response after
one dose of vaccine and a more mixed cytokine response after the
second dose. Split virus vaccine induced a type 2 response, particularly
after two vaccine doses. Our results show that two doses of vaccine
(both vaccine formulation) were more effective in induction of Th2
type of cytokines and thus indicate that both the formulation and
also the number of vaccine doses substantially influences the magnitude
and quality of the immune response.},
issn = {1365-3083},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3083.2006.01805.x}
}
@ARTICLE{Sa2011,
author = {Vanessa Karen de Sá and Eloísa Olivieri and Edwin Roger Parra and
Alexandre Muxfeldt Ab'Saber and Teresa Takagaki and Fernando Augusto
Soares and Dirce Carraro and Lina Carvalho and Vera Luiza Capelozzi},
title = {Hyaluronidase splice variants are associated with histology and outcome
in adenocarcinoma and squamous cell carcinoma of the lung},
journal = {Human Pathology},
year = {2011},
volume = {na},
pages = { - },
number = {0},
abstract = {Summary Heterogeneity of hyaluronidase (HYAL) expression has been
identified in tumors and shows promise as an indicator of disease
progression. The expression profile of alternatively spliced forms
of HYAL was evaluated in tumors and normal lung tissue from 69 resected
tumors of patients with adenocarcinomas and squamous cell carcinomas.
HYAL1-wild-type (wt) and variants 1 to 5, HYAL2-wt, and HYAL3-wt,
and variants 1 to 3 were identified by polymerase chain reaction
and direct sequencing. Different proportions of the 3 HYAL-wt and
variants were expressed in tumor and normal lung tissues. HYAL1-wt
was associated with a poorer prognosis and HYAL3-v1 with a better
prognosis. HYAL splice variants are associated with histology and
outcome, suggesting that strategies aimed at modulating their levels
may be effective for lung cancer treatment.},
doi = {10.1016/j.humpath.2011.06.010},
issn = {0046-8177},
keywords = {Hyaluronidases},
url = {http://www.sciencedirect.com/science/article/pii/S0046817711002826}
}
@ARTICLE{Saele2009,
author = {Sæle, Øystein and Nordgreen, Andreas and Hamre, Kristin and Olsvik,
Pål A.},
title = {Evaluation of candidate reference genes in Q-PCR studies of Atlantic
cod (Gadus morhua) ontogeny, with emphasis on the gastrointestinal
tract},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2009},
volume = {152},
pages = {94--101},
number = {1},
month = jan,
abstract = {To obtain reliable relative qPCR data in developing fish larvae, stable
reference genes have to be found. This study is focused on finding
good candidates for normalization of qPCR data for ontogenetic studies
of Atlantic cod. Ten commonly used reference genes; Acidic ribosomal
protein, Actin-related protein 2, [beta]-actin, Elongation factor
1 A, Glyceraldehyde-3-phosphate dehydrogenase, Ribosomal protein
37, Ribosomal protein 4, Ribosomal protein S9, [beta] 2-Tubulin and
Ubiquitin were analyzed in developing larvae from 3 to 97 day post
hatch (DPH). Two different tools were used to evaluate the stabilities
of these genes; the geNorm software ranks the most stable genes based
on a pair-wise analysis whereas NormFinder uses a model-based approach.
The same genes were also analyzed in GI tract homogenates and compared
to whole larvae homogenates. During Atlantic cod larval development
there are several strong candidates with Ubiquitin as the most stable.
The ribosomal proteins RPL4 and RPS9 are also strong candidates.
RPL37 may be used but only when normalizing qRT-PCR results from
one type of tissue. We also suggest the use of multiple genes for
normalization of qRT-PCR. Our study suggests that whole-larvae samples
can be used to study relative expression of genes that are expressed
only in certain tissues.},
issn = {1096-4959},
keywords = {Quantitative real-time PCR, Normalization, Development, GI tract,
Larvae},
url = {http://www.sciencedirect.com/science/article/B6T2R-4TNWH45-2/2/9abff189d97bda3d92a87cfa72054a7e}
}
@ARTICLE{Saele2010,
author = {Sæle, Øystein and Nordgreen, Andreas and Olsvik, Pål A. and Hamre,
Kristin},
title = {Characterization and expression of digestive neutral lipases during
ontogeny of Atlantic cod (Gadus morhua)},
journal = {Comparative Biochemistry and Physiology - Part A: Molecular \& Integrative
Physiology},
year = {2010},
volume = {157},
pages = {252--259},
number = {3},
month = nov,
abstract = {The major neutral lipase excreted by the pancreas in fish, is bile
activated lipase (BAL). Here we present evidence that cod have a
functional BAL and a non-functional pancreatic lipase related protein
(PLRP). The Atlantic cod genome does not seem to contain colipase
which is essential for pancreatic lipase activity. During the larval
stages, the gene expression of BAL was low until the point when pyloric
caeca started to differentiate and develop (~ 20 mm standard length
(SL)). Then the expression increased until ~ 50 mm SL. The PLRP gene
was expressed but showed very little regulation. The activity of
neutral lipase did not increase in parallel to gene expression. The
mismatch between activity and gene expression measurements may be
partly explained by the unspecific analytical method, when analysing
lipase activity in larva whole body. There is neutral lipase activity
in numerous tissues in the fish larvae and the lipase activity in
the gut, relatively to activity in the whole body, decreased with
age. Furthermore, neutral lipase activity in rotifers was ten times
higher than in whole cod larvae with full guts. Activity originating
from the live prey may therefore explain the high whole body lipase
activity from 3 to 20 dph. The results also indicate that "adult
type" digestion of neutral lipid develops late in the larval period
(from 20 mm SL), while other mechanisms of lipid uptake are active
at the early larval stage.},
issn = {1095-6433},
keywords = {Bile activated lipase, Carboxylic ester hydrolase, Pancreatic lipase,
Pancreatic lipase-related protein, Colipase},
url = {http://www.sciencedirect.com/science/article/B6VNH-50H1WVH-1/2/f4ae0c48fa00fbfcfc72644699802664}
}
@ARTICLE{Soederholm2011,
author = {Söderholm, H. and Lindström, M. and Somervuo, P. and Heap, J. and
Minton, N. and Lindén, J. and Korkeala, H.},
title = {cspB encodes a major cold shock protein in Clostridium botulinum
ATCC 3502},
journal = {International Journal of Food Microbiology},
year = {2011},
volume = {146},
pages = {23--30},
number = {1},
month = mar,
abstract = {The relative expression of three cold shock protein coding genes (cspA,
cspB and cspC) of Clostridium botulinum ATCC 3502 was studied with
quantitative RT-PCR analysis following a cold shock shift from 37 °C
to 15 °C. A significant increase in the relative expression of all
three genes was observed upon the temperature downshift. To validate
these findings, single-gene insertional inactivation of cspA, cspB
and cspC was undertaken with the ClosTron gene knock-out system.
In growth experiments, mutations in cspB or cspC, but not cspA, resulted
in a cold-sensitive phenotype. No growth of the cspB mutant was observed
at 15 °C over a ten day period, whereas at 20 °C the growth rate
was 70% lower than that of wild type strain. The growth rate of cspC
mutant was 70% and 80% lower than the growth rate of the wild type
strain at 15 °C and 20 °C, respectively. At 37 °C the growth of cspB
mutant did not differ from, but the growth rate of cspC mutant was
30% lower than, that of the wild type strain. The cspA mutant grew
somewhat faster than the wild type strain at all studied temperatures.
Since the inactivation of cspB resulted in the most prominent defect
in growth at low temperatures, we suggest that cspB encodes the major
cold shock protein of C. botulinum ATCC 3502. Understanding the mechanisms
behind cold tolerance of C. botulinum helps to evaluate the safety
risks this foodborne pathogen poses in the modern food industry.},
issn = {0168-1605},
keywords = {Clostridium botulinum, Cold shock protein, csp},
url = {http://www.sciencedirect.com/science/article/pii/S0168160511000407}
}
@ARTICLE{Soerensen2010,
author = {Sörensen, Meike and Mak, Tim N. and Hurwitz, Robert and Ogilvie,
Lesley A. and Mollenkopf, Hans J. and Meyer, Thomas F. and Brüggemann,
Holger},
title = {Mutagenesis of Propionibacterium acnes and analysis of two CAMP factor
knock-out mutants},
journal = {Journal of Microbiological Methods},
year = {2010},
volume = {83},
pages = {211--216},
number = {2},
month = nov,
abstract = {P. acnes is a skin commensal that is frequently associated with inflammatory
diseases such as acne vulgaris. Despite the availability of the genome
sequence functional studies on P. acnes are scarce due to a lack
of methods for genetic manipulation of this bacterium. Here we present
an insertional mutagenesis approach for the inactivation of specific
P. acnes genes. The gene of interest can be disrupted and replaced
with an erythromycin-resistance cassette by employing homologous
recombination. We used this method to generate knock-out mutants
of camp2 (PPA0687) and camp4 (PPA1231), encoding CAMP factor homologs
with predicted co-hemolytic activities. The successful inactivation
of the two genes was confirmed by PCR and Western blotting experiments
using specific anti-CAMP2/CAMP4 sera. The [Delta]camp2 but not the
[Delta]camp4 mutant exhibited reduced hemolytic activity in the CAMP
reaction with sheep erythrocytes, indicating that CAMP2 is the major
active co-hemolytic factor of P. acnes. The biological relevance
of the CAMP factors remains unclear as disruption of camp2 or camp4
did not significantly alter the transcriptome response of HaCaT cells
to P. acnes. The here presented insertional mutagenesis approach
will facilitate future studies on P. acnes.},
issn = {0167-7012},
keywords = {Propionibacterium acnes, Insertional mutagenesis, Co-hemolysin, acne
vulgaris},
url = {http://www.sciencedirect.com/science/article/B6T30-511R9H4-1/2/45a9d6c10b3c6de7c93c2228791cec7a}
}
@ARTICLE{Soefteland2009,
author = {Søfteland, Liv and Eide, Ingvar and Olsvik, Pål A.},
title = {Factorial design applied for multiple endpoint toxicity evaluation
in Atlantic salmon (Salmo salar L.) hepatocytes},
journal = {Toxicology in Vitro},
year = {2009},
volume = {23},
pages = {1455--1464},
number = {8},
month = dec,
abstract = {The toxic equivalent (TEQ) approach is traditionally used in risk
evaluation of dioxins. Non-dioxin-like PCBs are not included in this
approach and TEQ can therefore underestimate toxicity. In this study,
a factorial design and multiple endpoint strategy have been used
to evaluate the combined toxicity and possible interactions between
the non-dioxin-like PCB 138 and the potent AhR agonists 2,3,7,8-TCDF
(TCDF) and 1,2,3,7,8-PeCDD (PCDD). Primary hepatocyte cultures from
Atlantic salmon were exposed for 24 h and qPCR was employed to create
CYP1A dose-response curves and to quantify the transcriptional levels
of eight genes (CYP1A, UDPGT, HSP70, GR, GPX, MnSOD, GST and p53).
Principal component analysis (PCA) was used to evaluate response
similarities between genes. PLS regression was used to model CYP1A
and UDPGT responses to the three chemicals. The contour plot examinations
of the CYP1A model indicated an antagonism between PCDD and TCDF
and in the UDPGT model a possibly synergistic interaction between
PCB 138 and PCDD. The results indicate that PCB 138, in combination
with TCDF and PCDD, can contribute to the measured CYP1A and UDPGT
responses. Using primary cell cultures, multivariate data analysis
of qPCR data is shown to be a useful tool in toxicological studies.
A multiple endpoints strategy can enhance the quality of risk evaluation
of chemical compounds.},
booktitle = {Proceedings of ESTIV 2008, the 15th International Congress on In
Vitro Toxicology, 25 to 28 Sept 2008 Stockholm, Sweden},
issn = {0887-2333},
keywords = {Atlantic salmon hepatocytes, Gene expression, Dioxins, PCB 138, CYP1A,
UDPGT, Factorial design, TEQ},
url = {http://www.sciencedirect.com/science/article/B6TCP-4WS2HV8-3/2/ff981aca20a8b0b36f82bbdf710fd86d}
}
@ARTICLE{Soefteland2010,
author = {Søfteland, Liv and Holen, Elisabeth and Olsvik, Pål A.},
title = {Toxicological application of primary hepatocyte cell cultures of
Atlantic cod (Gadus morhua) -- Effects of BNF, PCDD and Cd},
journal = {Comparative Biochemistry and Physiology Part C: Toxicology \& Pharmacology},
year = {2010},
volume = {151},
pages = {401--411},
number = {4},
month = may,
abstract = {Fish primary hepatocyte cultures are commonly used for toxicological
assessment of contaminants. So far no one has described a protocol
on how to use Atlantic cod hepatocytes in bioassays. In this work
we describe an experiment in which we were able to isolate intact
liver cells from mature individuals. Hepatic cytochrome P450 1A (CYP1A)
expression in the isolated cells was evaluated with in situ hybridization
after intraperitoneal injection with the strong CYP1A inducer ß-naphthoflavone
(BNF). Cod hepatocytes were further exposed to 1,2,3,7,8-polychlorinated
dibenzo-p-dioxin (PCDD) and cadmium (Cd). Transcriptional responses
of 11 genes were quantified (CYP1A, metallothionein (MT), aryl hydrocarbon
receptor 2 (AhR2), UDP-glucuronosyltransferase (UGT), glutathione
S-transferase (GST), vitellogenin B (VTGB), hypoxia-inducible factor
1 (HIF1), heme oxygenase 1 (HO-1), transferrin, glutathione peroxidase
(GPx) and heat shock protein 70 (HSP70)). Immunohistochemisty evaluation
clearly showed elevated CYP1A mRNA expression in primary hepatocytes
isolated from BNF-exposed fish. The transcriptional results showed
that PCDD exposure resulted in a 311-fold up-regulation of CYP1A
and Cd a 1.82-fold increase of MT. Unexpectedly, AhR2 and UGT mRNA
levels were not significantly up-regulated in PCDD-exposed cod hepatocytes.
HO-1 and transferrin showed a dose-dependent transcriptional response
to Cd exposure. Cd appears to act as an endocrine-disrupting metal
in exposed primary Atlantic cod hepatocytes. This study demonstrates
the use of Atlantic cod primary hepatocyte cultures in toxicological
research.},
issn = {1532-0456},
keywords = {Atlantic cod primary hepatocyte culture, Bioassay, BNF, Cd, PCDD,
Exposure, CYP1A, MT, HO-1},
url = {http://www.sciencedirect.com/science/article/B6W89-4Y4PVNN-1/2/24e5eddabaf6cb2a42f3e868da304352}
}
@ARTICLE{Soefteland2011,
author = {Søfteland, Liv and Petersen, Kjell and Stavrum, Anne-Kristin and
Wu, Terence and Olsvik, Pål A.},
title = {Hepatic in vitro toxicity assessment of PBDE congeners BDE47, BDE153
and BDE154 in Atlantic salmon (Salmo salar L.)},
journal = {Aquatic Toxicology},
year = {2011},
volume = {105, 3-4},
pages = {246–263},
abstract = {The brominated flame retardant congeners BDE47, BDE153 and BDE154
are among the congeners accumulating to the highest degree in fish.
In order to gain knowledge about the toxicological effects of PBDEs
in fish, microarray-based transcriptomic and 2D-DIGE/ MALDI-TOF/TOF
proteomic approaches were used to screen for effects in primary Atlantic
salmon hepatocytes exposed to these congeners alone or in combination
(PBDE-MIX). A small set of stress related transcripts and proteins
were differentially expressed in the PBDE exposed hepatocytes. The
PBDE-MIX, and BDE153 to a lesser degree, seems to have induced metabolic
disturbances by affecting several pathways related to glucose homeostasis.
Further, effects on cell cycle control and proliferation signal pathways
in PBDE-MIX-exposed hepatocytes clearly suggest that the PBDE exposure
affected cell proliferation processes. CYP1A was 7.41- and 7.37-fold
up-regulated in hepatocytes exposed to BDE47 and PBDE-MIX respectively,
and was the only biotransformation pathway affected by the PBDE exposure.
The factorial design and PLS regression analyses of the effect of
the PBDE-MIX indicated that BDE47 contributed the most to the observed
CYP1A response, suggesting that this congener should be incorporated
in the toxic equivalent (TEQ) concept in future risk assessment of
dioxin-like chemicals. Additionally, a significant up-regulation
of the ER-responsive genes VTG and ZP3 were observed in cells exposed
to BDE47 and PBDE-MIX. Further analyses suggested that BDE47 and
BDE154 have an estrogenic effect in male fish. The data also suggested
an antagonistic interaction between BDE153 and BDE154. In conclusion,
this study shows that PBDEs can affect several biological systems
in Atlantic salmon cells, and demonstrates the need for more studies
on the simultaneous exposure to chemical mixtures to identify combined
effects of chemicals.},
issn = {0166-445X},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X11000919}
}
@ARTICLE{Taaffe2011,
author = {Taaffe, Jessica E. and Bosinger, Steven E. and Del Prete, Gregory
Q. and Else, James G. and Ratcliffe, Sarah and Ward, Christopher
D. and Migone, Thi and Paiardini, Mirko and Silvestri, Guido},
title = {CCR5 blockade is well tolerated and induces changes in the tissue
distribution of CCR5+ and CD25+ T cells in healthy, SIV-uninfected
rhesus macaques},
journal = {Journal of Medical Primatology},
year = {2011},
pages = {no--no},
abstract = {Background  CCR5 is a main co-receptor for HIV, but also homes lymphocytes
to sites of inflammation. We hypothesized that inhibition of CCR5
signaling would reduce HIV-associated chronic immune activation.Methods 
To test this hypothesis, we administered an antagonistic anti-CCR5
monoclonal antibody (HGS101) to five uninfected rhesus macaques (RMs)
and monitored lymphocyte dynamics in blood and tissue.Results 
CCR5 blockade resulted in decreased levels of CCR5+ T cells in blood
and, at later timepoints, in lymph nodes. Additionally, the levels
of CD25+ T cells increased in lymph nodes, but decreased in blood,
bone marrow, and rectal mucosa. Finally, a profile of gene expression
from HGS101-treated RMs revealed a subtle, but consistent, in vivo
signature of CCR5 blockade that suggests a mild immune-modulatory
effect.Conclusions  Treatment with anti-CCR5 antibody induces changes
in the tissue distribution of CCR5+ and CD25+ T cells that may impact
on the overall levels of immune activation during HIV and SIV infection.},
doi = {10.1111/j.1600-0684.2011.00521.x},
issn = {1600-0684},
keywords = {HIV, immune activation, trafficking},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0684.2011.00521.x}
}
@ARTICLE{Tabakoff2009,
author = {Tabakoff, Boris and Saba, Laura and Printz, Morton and Flodman, Pam
and Hodgkinson, Colin and Goldman, David and Koob, George and Richardson,
Heather and Kechris, Katerina and Bell, Richard and Hübner, Norbert
and Heinig, Matthias and Pravenec, Michal and Mangion, Jonathan and
Legault, Lucie and Dongier, Maurice and Conigrave, Katherine and
Whitfield, John and Saunders, John and Grant, Bridget and Hoffman,
Paula and WHO/ISBRA Study on State and Trait Markers of Alcoholism},
title = {Genetical genomic determinants of alcohol consumption in rats and
humans},
journal = {BMC Biology},
year = {2009},
volume = {7},
pages = {70},
number = {1},
abstract = {BACKGROUND:We have used a genetical genomic approach, in conjunction
with phenotypic analysis of alcohol consumption, to identify candidate
genes that predispose to varying levels of alcohol intake by HXB/BXH
recombinant inbred rat strains. In addition, in two populations of
humans, we assessed genetic polymorphisms associated with alcohol
consumption using a custom genotyping array for 1,350 single nucleotide
polymorphisms (SNPs). Our goal was to ascertain whether our approach,
which relies on statistical and informatics techniques, and non-human
animal models of alcohol drinking behavior, could inform interpretation
of genetic association studies with human populations.RESULTS:In
the HXB/BXH recombinant inbred (RI) rats, correlation analysis of
brain gene expression levels with alcohol consumption in a two-bottle
choice paradigm, and filtering based on behavioral and gene expression
quantitative trait locus (QTL) analyses, generated a list of candidate
genes. A literature-based, functional analysis of the interactions
of the products of these candidate genes defined pathways linked
to presynaptic GABA release, activation of dopamine neurons, and
postsynaptic GABA receptor trafficking, in brain regions including
the hypothalamus, ventral tegmentum and amygdala. The analysis also
implicated energy metabolism and caloric intake control as potential
influences on alcohol consumption by the recombinant inbred rats.
In the human populations, polymorphisms in genes associated with
GABA synthesis and GABA receptors, as well as genes related to dopaminergic
transmission, were associated with alcohol consumption.CONCLUSION:Our
results emphasize the importance of the signaling pathways identified
using the non-human animal models, rather than single gene products,
in identifying factors responsible for complex traits such as alcohol
consumption. The results suggest cross-species similarities in pathways
that influence predisposition to consume alcohol by rats and humans.
The importance of a well-defined phenotype is also illustrated. Our
results also suggest that different genetic factors predispose alcohol
dependence versus the phenotype of alcohol consumption.},
doi = {10.1186/1741-7007-7-70},
issn = {1741-7007},
pubmedid = {19874574},
url = {http://www.biomedcentral.com/1741-7007/7/70}
}
@ARTICLE{Tabatabaie2009,
author = {Tabatabaie, L. and de Koning, T.J. and Geboers, A.J.J.M. and van
den Berg, I.E.T. and Berger, R. and Klomp, L.W.J.},
title = {Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed
throughout the protein and result in altered enzyme kinetics},
journal = {Hum. Mutat.},
year = {2009},
volume = {30},
pages = {749--756},
number = {5},
abstract = {Abstract 10.1002/humu.20934.abs Three-phosphoglycerate dehydrogenase
(3-PGDH) deficiency is a rare recessive inborn error in the biosynthesis
of the amino acid L-serine characterized clinically by congenital
microcephaly, psychomotor retardation, and intractable seizures.
The biochemical abnormalities associated with this disorder are low
concentrations of L-serine, D-serine, and glycine in cerebrospinal
fluid (CSF). Only two missense mutations (p.V425M and p.V490M) have
been identified in PHGDH, the gene encoding 3-PGDH, but it is currently
unclear how these mutations in the carboxy-terminal regulatory domain
of the protein affect enzyme function. We now describe five novel
mutations in five patients with 3-PGDH deficiency; one frameshift
mutation (p.G238fsX), and four missense mutations (p.R135W, p.V261M,
p.A373T, and p.G377S). The missense mutations were located in the
nucleotide binding and regulatory domains of 3-PGDH and did not affect
steady-state expression, protein stability, and protein degradation
rates. Patients' fibroblasts displayed a significant, but incomplete,
reduction in maximal enzyme activities associated with all missense
mutations. In transient overexpression studies in HEK293T cells,
the p.A373T, p.V425M, and p.V490M mutations resulted in almost undetectable
enzyme activities. Molecular modeling of the p.R135W and p.V261M
mutations onto the partial crystal structure of 3-PGDH predicted
that these mutations affect substrate and cofactor binding. This
prediction was confirmed by the results of kinetic measurements in
fibroblasts and transiently transfected HEK293T cells, which revealed
a markedly decreased Vmax and an increase in Km values, respectively.
Taken together, these data suggest that missense mutations associated
with 3-PGDH deficiency either primarily affect substrate binding
or result in very low residual enzymatic activity. Hum Mutat 0, 1–8,
2009. © 2009 Wiley-Liss, Inc.},
issn = {1098-1004},
keywords = {PHGDH, 3-PGDH deficiency, serine deficiency, kinetics},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/humu.20934}
}
@ARTICLE{Tabernero2007,
author = {Tabernero, Maria Dolores and Espinosa, Ana Belen and Maillo, Angel
and Rebelo, Olinda and Vera, Jaime Fernandez and Sayagues, Jose Maria
and Merino, Marta and Diaz, Pedro and Sousa, Pablo and Orfao, Alberto},
title = {Patient Gender Is Associated with Distinct Patterns of Chromosomal
Abnormalities and Sex Chromosome Linked Gene-Expression Profiles
in Meningiomas},
journal = {Oncologist},
year = {2007},
volume = {12},
pages = {1225--1236},
number = {10},
month = oct,
abstract = {The female predominance of meningiomas has been established, but how
this is affected by hormones is still under discussion. We analyzed
the characteristics of meningiomas from male (n = 53) and female
(n = 111) patients by interphase fluorescence in situ hybridization
(iFISH). In addition, in a subgroup of 45 (12 male and 33 female)
patients, tumors were hybridized with the Affymetrix U133A chip.
We show a higher frequency of larger tumors (p = .01) and intracranial
meningiomas (p = .04) together with a higher relapse rate (p = .03)
in male than in female patients. Male patients had a higher percentage
of del(1p36) (p < .001), while loss of an X chromosome was restricted
to tumors from female patients (p = .008). In turn, iFISH studies
showed a higher frequency of chromosome losses, other than monosomy
22 alone, in meningiomas from male patients (p = .002), while female
patients displayed a higher frequency of chromosome gains (p = .04)
or monosomy 22 alone (p = .03) in the ancestral tumor clone. Interestingly,
individual chromosomal abnormalities had a distinct impact on the
recurrence-free survival rate of male versus female patients. In
turn, gene expression showed that eight genes (RPS4Y1, DDX3Y, JARID1D,
DDX3X, EIF1AY, XIST, USP9Y, and CYorf15B) had significantly different
expression patterns (R2 > 0.80; p < .05) in tumors from male and
female patients. In summary, we show the existence of different patterns
of chromosome abnormalities and gene-expression profiles associated
with patient gender, which could help to explain the slightly different
clinical behavior of these two patient groups.},
url = {http://theoncologist.alphamedpress.org/cgi/content/abstract/12/10/1225}
}
@ARTICLE{Tabernero2009,
author = {Tabernero, Maria Dolores and Maillo, Angel and Gil-Bellosta, Carlos
J. and Castrillo, Abel and Sousa, Pablo and Merino, Marta and Orfao,
Alberto},
title = {Gene Expression Profiles of Meningiomas are Associated with Tumor
Cytogenetics and Patient Outcome},
journal = {Brain Pathology},
year = {2009},
volume = {19},
pages = {409--420},
number = {3},
abstract = {Abstract Cytogenetic analysis is a powerful tool for predicting recurrence
in meningiomas, even among histologically benign/grade I tumors.
Despite this, no study has been reported in which the impact of tumor
cytogenetics on the gene expression profiles (GEP) has been analyzed
in meningiomas. Here, we analyzed the GEP of 47 tumors and correlated
them with the most clinical relevant cytogenetic subgroups of meningiomas,
as confirmed through the analysis of 172 patients. Additionally three
normal meningeal samples were also studied. Overall, our results
show a clear association between the clinically relevant cytogenetic
subgroups of meningiomas including diploid tumors (n = 18), isolated
−22/22q− (n = 12), del(1p36) alone (n = 4) and complex karyotypes
associated with del(1p36) and/or −14q (n = 13) and their GEP.
Accordingly, based on the expression of 85 genes (40 of which were
coded in the altered chromosomes used for patient stratification)
the cytogenetic class of the tumor could be predicted with an error
of <1%, a clear association being found between the GEP and patient
outcome (PÂ =Â 0.03) but not tumor histopathology. In summary, we
show a clear association between GEP of neoplastic cells and clinically
relevant cytogenetic subgroups of meningiomas.},
issn = {1750-3639},
keywords = {array, cytogenetics, gene expression, histopathology, meningioma},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2008.00191.x}
}
@ARTICLE{Tabibiazar2005,
author = {Tabibiazar, Raymond and Wagner, Roger A. and Ashley, Euan A. and
King, Jennifer Y. and Ferrara, Rossella and Spin, Joshua M. and Sanan,
David A. and Narasimhan, Balasubramanian and Tibshirani, Robert and
Tsao, Philip S. and Efron, Bradley and Quertermous, Thomas},
title = {Signature patterns of gene expression in mouse atherosclerosis and
their correlation to human coronary disease},
journal = {Physiol Genomics},
year = {2005},
volume = {22},
pages = {213--226},
number = {2},
month = jul,
abstract = {The propensity for developing atherosclerosis is dependent on underlying
genetic risk and varies as a function of age and exposure to environmental
risk factors. Employing three mouse models with different disease
susceptibility, two diets, and a longitudinal experimental design,
it was possible to manipulate each of these factors to focus analysis
on genes most likely to have a specific disease-related function.
To identify differences in longitudinal gene expression patterns
of atherosclerosis, we have developed and employed a statistical
algorithm that relies on generalized regression and permutation analysis.
Comprehensive annotation of the array with ontology and pathway terms
has allowed rigorous identification of molecular and biological processes
that underlie disease pathophysiology. The repertoire of atherosclerosis-related
immunomodulatory genes has been extended, and additional fundamental
pathways have been identified. This highly disease-specific group
of mouse genes was combined with an extensive human coronary artery
data set to identify a shared group of genes differentially regulated
among atherosclerotic tissues from different species and different
vascular beds. A small core subset of these differentially regulated
genes was sufficient to accurately classify various stages of the
disease in mouse. The same gene subset was also found to accurately
classify human coronary lesion severity. In addition, this classifier
gene set was able to distinguish with high accuracy atherectomy specimens
from native coronary artery disease vs. those collected from in-stent
restenosis lesions, thus identifying molecular differences between
these two processes. These studies significantly focus efforts aimed
at identifying central gene regulatory pathways that mediate atherosclerotic
disease, and the identification of classification gene sets offers
unique insights into potential diagnostic and therapeutic strategies
in atherosclerotic disease.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/22/2/213}
}
@ARTICLE{Taboada2012,
author = {Xoana Taboada and Diego Robledo and Lorena Del Palacio and Antonio
Rodeiro and Alicia Felip and Paulino MartÃnez and Ana Viñas},
title = {Comparative expression analysis in mature gonads, liver and brain
of turbot (Scophthalmus maximus) by cDNA-AFLPS},
journal = {Gene},
year = {2012},
volume = {492},
pages = {250 - 261},
number = {1},
abstract = {Turbot is one of the most important farmed fish in Europe. This species
exhibits a considerable sexual dimorphism in growth and sexual maturity
that makes the all-female production recommended for turbot farming.
Our knowledge about the genetic basis of sex determination and the
molecular regulation of gonad differentiation in this species is
still limited. Our goal was to identify and compare gene expression
and functions between testes and ovaries in adults in order to ascertain
the relationship between the genes that could be involved in the
gonad differentiation or related to the sex determination system.
The identification of differentially expressed sex related genes
is an initial step towards understanding the molecular mechanisms
of gonad differentiation. For this, we carried out a transcriptome
analysis based on cDNA-AFLP technique which allowed us to obtain
an initial frame on sex-specific gene expression that will facilitate
further analysis especially along the critical gonad differentiating
period. With the aim of widening the study on sex-biased gene expression
we reproduced the same experiments in two somatic tissues: liver
and brain. We have selected the liver because it is the most analyzed
one regarding sexual dimorphic gene expression and due to its importance
in steroid hormones metabolism and the brain because the functional
relationship between brain and gonad is documented. We found slight
but important differences between sexes which deserve further investigation.},
doi = {10.1016/j.gene.2011.10.020},
issn = {0378-1119},
keywords = {DNA markers},
url = {http://www.sciencedirect.com/science/article/pii/S037811191100597X}
}
@ARTICLE{Tabor2011,
author = {Tabor, Mark H. and Clay, Matthew R. and Owen, John H. and Bradford,
Carol R. and Carey, Thomas E. and Wolf, Gregory T. and Prince, Mark
E.},
title = {Head and neck cancer stem cells: The side population},
journal = {The Laryngoscope},
year = {2011},
volume = {121},
pages = {527--533},
number = {3},
abstract = {Abstract Objectives/Hypothesis:The cancer stem cell (CSC) theory concludes
that a subpopulation of cancer cells, the cancer stem cells, can
self-renew and are responsible for tumor growth. Previous studies
have identified cells able to efflux Hoechst 33342 dye as the side
population (SP). SP cells and CSCs share many characteristics, suggesting
the SP isolated from malignant tumors contains CSCs.Study Design:Experimental
Study.Methods:The SP was isolated from a head and neck cancer cell
line and analyzed for CSC-like characteristics.Results:The SP demonstrated
the ability to reproduce both SP and non-side population (NSP) cells
from as few as one cell. The SP had lower expression of active β-catenin
and more resistance to 5-fluorouracil; the SP also demonstrated greater
expression of Bmi-1 (4.3-fold) and ABCG2 (1.4-fold). SP cells were
able to produce tumors in an animal model, whereas NSP were not.
SPs were identified in two primary human tumors.Conclusions:This
work adds to the evidence that the SP in head and neck cancer represents
cells with CSC properties and provides a method by which CSCs can
be isolated and studied. Laryngoscope, 2011},
doi = {10.1002/lary.21032},
issn = {1531-4995},
keywords = {Head and neck cancer, cancer stem cell, side population, Hoechst 33342,
Bmi-1, Level of Evidence: 1c},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/lary.21032}
}
@ARTICLE{Tabruyn2007,
author = {Tabruyn, Sebastien P. and Sabatel, Celine and Nguyen, Ngoc-Quynh-Nhu
and Verhaeghe, Catherine and Castermans, Karolien and Malvaux, Ludovic
and Griffioen, Arjan W. and Martial, Joseph A. and Struman, Ingrid},
title = {The Angiostatic 16K Human Prolactin Overcomes Endothelial Cell Anergy
and Promotes Leukocyte Infiltration via Nuclear Factor-{kappa}B Activation},
journal = {Mol. Endocrinol.},
year = {2007},
volume = {21},
pages = {1422--1429},
number = {6},
month = jun,
abstract = {The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a
potent angiostatic factor that inhibits tumor growth in mouse models.
Using microarray experiments, we have dissected how the endothelial-cell
genome responds to 16K hPRL treatment. We found 216 genes that show
regulation by 16K hPRL, of which a large proportion turned out to
be associated with the process of immunity. 16K hPRL induces expression
of various chemokines and endothelial adhesion molecules. These expressions,
under the control of nuclear factor-{kappa}B, result in an enhanced
leukocyte-endothelial cell interaction. Furthermore, analysis of
B16-F10 tumor tissues reveals a higher expression of adhesion molecules
(intercellular adhesion molecule 1, vascular cell adhesion molecule
1, or E-selectin) in endothelial cells and a significantly higher
number of infiltrated leukocytes within the tumor treated with 16K
hPRL compared with the untreated ones. In conclusion, this study
describes a new antitumor mechanism of 16K hPRL. Because cellular
immunity against tumor cells is a crucial step in therapy, the discovery
that treatment with 16K hPRL overcomes tumor-induced anergy may become
important for therapeutic perspectives.},
url = {http://mend.endojournals.org/cgi/content/abstract/21/6/1422}
}
@ARTICLE{Tabuchi2004,
author = {Tabuchi, Mari and Baba, Yoshinobu},
title = {Self-Contained On-Chip Cell Culture and Pretreatment System},
journal = {Journal of Proteome Research},
year = {2004},
volume = {3},
pages = {871-877},
number = {4},
note = {PMID: 15359743},
doi = {10.1021/pr0499500},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr0499500},
url = {http://pubs.acs.org/doi/abs/10.1021/pr0499500}
}
@ARTICLE{Tabuchi2003,
author = {Tabuchi, Mari and Kuramitsu, Yasuhiro and Nakamura, Kazuyuki and
Baba, Yoshinobu},
title = {Rapid Subpicogram Protein Detection on a Microchip without Denaturing},
journal = {Journal of Proteome Research},
year = {2003},
volume = {2},
pages = {431-435},
number = {4},
doi = {10.1021/pr034009m},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr034009m},
url = {http://pubs.acs.org/doi/abs/10.1021/pr034009m}
}
@ARTICLE{Tabuse2011,
author = {Tabuse, Masanao and Ohta, Shigeki and Ohashi, Yohei and Fukaya, Raita
and Misawa, Aya and Yoshida, Kazunari and Kawase, Takeshi and Saya,
Hideyuki and Thirant, Cecile and Chneiweiss, Herve and Matsuzaki,
Yumi and Okano, Hideyuki and Kawakami, Yutaka and Toda, Masahiro},
title = {Functional analysis of HOXD9 in human gliomas and glioma cancer stem
cells},
journal = {Molecular Cancer},
year = {2011},
volume = {10},
pages = {60},
number = {1},
abstract = {BACKGROUND:HOX genes encode a family of homeodomain-containing transcription
factors involved in the determination of cell fate and identity during
embryonic development. They also behave as oncogenes in some malignancies.RESULTS:In
this study, we found high expression of the HOXD9 gene transcript
in glioma cell lines and human glioma tissues by quantitative real-time
PCR. Using immunohistochemistry, we observed HOXD9 protein expression
in human brain tumor tissues, including astrocytomas and glioblastomas.
To investigate the role of HOXD9 in gliomas, we silenced its expression
in the glioma cell line U87 using HOXD9-specific siRNA, and observed
decreased cell proliferation, cell cycle arrest, and induction of
apoptosis. It was suggested that HOXD9 contributes to both cell proliferation
and/or cell survival. The HOXD9 gene was highly expressed in a side
population (SP) of SK-MG-1 cells that was previously identified as
an enriched-cell fraction of glioma cancer stem-like cells. HOXD9
siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation.
Finally, we cultured human glioma cancer stem cells (GCSCs) from
patient specimens found with high expression of HOXD9 in GCSCs compared
with normal astrocyte cells and neural stem/progenitor cells (NSPCs).CONCLUSIONS:Our
results suggest that HOXD9 may be a novel marker of GCSCs and cell
proliferation and/or survival factor in gliomas and glioma cancer
stem-like cells, and a potential therapeutic target.},
doi = {10.1186/1476-4598-10-60},
issn = {1476-4598},
pubmedid = {21600039},
url = {http://www.molecular-cancer.com/content/10/1/60}
}
@ARTICLE{Tacchi2011,
author = {Luca Tacchi and Ralph Bickerdike and Alex Douglas and Christopher
J. Secombes and Samuel A.M. Martin},
title = {Transcriptomic responses to functional feeds in Atlantic salmon (Salmo
salar)},
journal = {Fish \& Shellfish Immunology},
year = {2011},
volume = {31},
pages = {704 - 715},
number = {5},
note = {1st EOFFI Symposium},
abstract = {Functional feeds are diets that have positive effects on both health
and growth promoting performance of the animals ingesting them, by
supplying additional compounds above and beyond the basic nutritional
requirements for animal growth alone. The most common additives used
in aquaculture diets are probiotics, prebiotics, immunostimulants,
vitamins and nucleotides. Inclusion of these components to fish diets
can increase feed conversion efficiency and growth, as well as having
positive effects on the fish immune system. This review discusses
the results from previous studies on fish nutrition and includes
a novel genomic approach, using microarray analysis, to elucidate
nutritional responses in Atlantic salmon (Salmo salar) fed a newly
developed functional feed health premix diet. The transcriptome analysis
demonstrated that compared to the standard diet feeding with the
functional feed had significant effects on biological processes in
the liver. This resulted in a reduction of the expression of genes
related to protein turnover, reduced circulating plasma proteins
and a down regulation of genes involved in the immune response. These
results suggest that the functional feed may infer a decrease in
whole body metabolic demands, suppressing both protein turnover and
whole body oxygen demand, as well as down regulating several genes
involved in the innate immune system. Together these changes appear
to result in less energy wastage in fish and an enhanced growth and
performance.},
doi = {10.1016/j.fsi.2011.02.023},
issn = {1050-4648},
keywords = {Atlantic salmon},
url = {http://www.sciencedirect.com/science/article/pii/S1050464811000866}
}
@ARTICLE{Tacchi2010,
author = {Tacchi, Luca and Bickerdike, Ralph and Secombes, Christopher J. and
Pooley, Nicholas J. and Urquhart, Katy L. and Collet, Bertrand and
Martin, Samuel A.M.},
title = {Ubiquitin E3 ligase atrogin-1 (Fbox-32) in Atlantic salmon (Salmo
salar): Sequence analysis, genomic structure and modulation of expression},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2010},
volume = {157},
pages = {364--373},
number = {4},
month = dec,
abstract = {E3 ubiquitin ligases are central for the selection of proteins targeted
for degradation by the ubiquitin proteasome pathway. In this study
atrogin-1 (Fbox-32), a major E3 ligase in muscle, has been characterized
in Atlantic salmon (Salmo salar). The protein sequence is highly
conserved between teleosts and mammals and is characterized by the
presence of five conserved motifs related to the identification of
protein targets. The genomic structure is conserved between teleosts
and mammals and contains 9 exon and 8 introns. The phylogenetic relationship
between atrogin-1 and two other closely related ubiquitin E3 ligases
FBXO25 and MuRF1 showed atrogin-1 and FBXO25 grouped together with
MuRF1 being more distant. The mRNAs were expressed in multiple tissues,
atrogin-1 and MuRF1 were most abundant in white muscle and heart
whereas FBXO25 had greatest expression in brain, white muscle and
heart. The transcriptional modulation of these E3 ligases was examined
in starved fish and fish following different immune stimulations.
Expression of atrogin-1 and MuRF1 was increased following food deprivation,
implementing these two genes in degradation of muscle protein during
starvation. During viral infection atrogin-1 expression was not altered,
whereas it was increased following stimulation with LPS, indicating
an onset of catabolic processes during inflammatory responses.},
issn = {1096-4959},
keywords = {Atlantic salmon, Proteasome, Atrogin-1, Protein degradation, E3 ubiquitin
ligase},
url = {http://www.sciencedirect.com/science/article/B6T2R-50TRXDF-2/2/3a08ffbea740d44090ccd012724d0e48}
}
@ARTICLE{Tacchi2011a,
author = {Tacchi, Luca and Bron, James E. and Taggart, John B. and Secombes,
Christopher J. and Bickerdike, Ralph and Adler, Michael A. and Takle,
Harald and Martin, Samuel A. M.},
title = {Multiple tissue transcriptomic responses to Piscirickettsia salmonis
in Atlantic salmon (Salmo salar)},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {1241-1254},
number = {21},
abstract = {The bacterium Piscirickettsia salmonis is the etiological agent of
salmonid rickettsial septicemia (SRS), a severe disease that causes
major economic losses to the Atlantic salmon aquaculture industry
every year. Little is known about the infective strategy of P. salmonis,
which is able to infect, survive within, and replicate inside salmonid
macrophages as an intracellular parasite. Similarly there is little
knowledge concerning the fish host's response to invasion by this
pathogen. We have examined the transcriptional response of postsmolt
Atlantic salmon (Salmo salar) to P. salmonis at 48 h following infection
in three tissues, liver, head kidney, and muscle, using an Atlantic
salmon oligonucleotide microarray (Salar_2, Agilent 4x44K). The infection
led to a large alteration of transcriptional activity in all the
tissues studied. In infected salmon 886, 207, and 153 transcripts
were differentially expressed in liver, head kidney, and muscle,
respectively. Assessment of enrichment for particular biological
pathways by gene ontology analysis showed an upregulation of genes
involved in oxidative and inflammatory responses in infected fish,
indicative of the activation of the innate immune response. The downregulation
of genes involved in the adaptive immune response, G protein signaling
pathway, and apoptotic process in infected fish may be reflective
of mechanisms used by P. salmonis to survive, replicate, and escape
host defenses. There was also evidence of differential responses
between studied tissues, with protein metabolism being decreased
in muscle of infected fish and with a concomitant increase being
shown in liver.},
doi = {10.1152/physiolgenomics.00086.2011},
eprint = {http://physiolgenomics.physiology.org/cgi/reprint/43/21/1241.pdf},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/21/1241}
}
@ARTICLE{Tacchi2011b,
author = {Luca Tacchi and Elisa Casadei and Ralph Bickerdike and Christopher
J. Secombes and Samuel A.M. Martin},
title = {Cloning and expression analysis of the Mitochondrial Ubiquitin Ligase
Activator of NF-κB (MULAN) in Atlantic salmon (Salmo salar)},
journal = {Molecular Immunology},
year = {2011},
volume = {49},
pages = {558 - 565},
number = {3},
abstract = {Nuclear factor-κB (NF-κB) is a transcription factor involved in
the regulation of a large number of genes including many involved
in bacterial and viral infections. NF-κB is normally sequestered
by inhibitory proteins (IκBs) in the cytoplasm of non-stimulated
cells. The degradation of IκBs by the ubiquitin proteasome pathway
leads to the rapid translocation of NF-κB to the nucleous where
it regulates gene transcription. The Mitochondrial Ubiquitin Ligase
Activator of NF-κB, (MULAN), is an E3 ubiquitin ligase believed
to be central in controlling activation of NF-κB, and regulating
the mitochondrial dynamics and apoptosis process. We report, for
the first time in fish, the characterization of a MULAN cDNA in Atlantic
salmon and rainbow trout. The salmonid MULAN sequences encode predicted
proteins of 352 amino acids. The mRNA of MULAN was expressed in multiple
tissues, with the highest abundance in brain and white muscle. An
Aeromonas salmonicida bacterial challenge increased expression of
this gene in head kidney, liver and gill both at 6 and at 24 h
following the infection. In vitro experiments using the salmonid
cell line RTG-2 indicated MULAN was increased in expression following
4 h stimulation with LPS and recombinant trout IL-1β. MULAN
expression remained increased 24 h post-stimulation with both
LPS and IL-1β, but was down regulated by PolyI:C at this time. These
results suggest an active role of the MULAN gene in the activation
of the NF-κB pathway during piscine immune responses.},
doi = {10.1016/j.molimm.2011.10.005},
issn = {0161-5890},
keywords = {Atlantic salmon},
url = {http://www.sciencedirect.com/science/article/pii/S016158901100784X}
}
@ARTICLE{Taccioli2009,
author = {Taccioli, Cristian and Wan, Shao-Gui and Liu, Chang-Gong and Alder,
Hansjuerg and Volinia, Stefano and Farber, John L. and Croce, Carlo
M. and Fong, Louise Y.Y.},
title = {Zinc Replenishment Reverses Overexpression of the Proinflammatory
Mediator S100A8 and Esophageal Preneoplasia in the Rat},
journal = {Gastroenterology},
year = {2009},
volume = {136},
pages = {953--966},
number = {3},
month = mar,
abstract = {Background & Aims Zinc deficiency is implicated in the pathogenesis
of human esophageal cancer. In the rat esophagus, it induces cell
proliferation, modulates genetic expression, and enhances carcinogenesis.
Zinc-replenishment reverses proliferation and inhibits carcinogenesis.
The zinc-deficient rat model allows the identification of biological
differences affected by zinc during early esophageal carcinogenesis.Methods
We evaluated gene expression profiles of esophageal epithelia from
zinc-deficient and replenished rats vs zinc-sufficient rats using
microarray analysis. We characterized the role of the top-up-regulated
gene S100A8 in esophageal hyperplasia/reversal and in chemically
induced esophageal carcinogenesis in zinc-modulated animals by immunohistochemistry
and real-time quantitative polymerase chain reaction.Results The
hyperplastic-deficient esophagus has a distinct expression signature
with the proinflammation genes S100 calcium binding protein A8 (S100A8)
and A9 (S100A9) up-regulated 57-fold and 5-fold, respectively. Zinc
replenishment rapidly restored to control levels the expression of
S100A8/A9 and 27 other genes and reversed the hyperplastic phenotype.
With its receptor for advanced glycation end products (RAGE), colocalization
and overexpression of S100A8 protein occurred in the deficient esophagus
that overexpressed nuclear factor [kappa][Beta] p65 and cyclooxygenase-2
(COX-2) protein. Zinc replenishment, but not a COX-2 inhibitor, reduced
the overexpression of these 4 proteins. Additionally, esophageal
S100A8/A9 messenger RNA levels were associated directly with the
diverse tumorigenic outcome in zinc-deficient and zinc-replenished
rats.Conclusions In vivo zinc regulates S100A8 expression and modulates
the link between S100A8-RAGE interaction and downstream nuclear factor
[kappa][Beta]/COX-2 signaling. The finding that zinc regulates an
inflammatory pathway in esophageal carcinogenesis may lead to prevention
and therapy for this cancer.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4V0MM79-2/2/50829f4c67854f6a79cfad594fa62667}
}
@ARTICLE{Tachikawa2008,
author = {Tachikawa, Kashiko and Sasaki, Shinji and Maeda, Takuya and Nakajima,
Kazunori},
title = {Identification of molecules preferentially expressed beneath the
marginal zone in the developing cerebral cortex},
journal = {Neuroscience Research},
year = {2008},
volume = {60},
pages = {135--146},
number = {2},
month = feb,
abstract = {During cerebral cortical development, the majority of excitatory neurons
are born near the ventricle and migrate radially toward the marginal
zone (MZ). Since the cells invariably stop migrating beneath the
MZ, neurons are aligned in an "inside-out" manner in the cortical
plate (CP); that is, the early-born and late-born neurons are ultimately
positioned in the deep and superficial layers, respectively. Since
dramatic morphological changes occur in cells beneath the MZ, several
events critical for proper neuronal maturation and layer formation
must take place. In this study, we screened for molecules strongly
expressed beneath the MZ, and identified 28 genes that are preferentially
expressed in the upper half of the mouse CP on both embryonic day
(E) 16.5 and E18.5. Expression analyses in reeler and yotari mice,
in which neurons terminate migration throughout the CP, suggested
that these genes were indeed related to the events beneath the MZ
rather than unrelatedly induced by the structures near the brain
surface. Pathway analyses suggested calcium signaling to have an
important role in cells beneath the MZ. The gene list presented here
will be useful for clarifying the molecular mechanisms that control
cortical development.},
issn = {0168-0102},
keywords = {Cerebral cortex, Neuronal migration, Marginal zone, DNA microarray,
Calcium signal, Protein-protein interaction (PPI)},
url = {http://www.sciencedirect.com/science/article/B6T0H-4R063TC-1/2/c2a771f3daa5e8e1d2676c2d6e18d5f1}
}
@ARTICLE{Tacon2009,
author = {Tacon, Lyndal J. and Soon, Patsy S. and Gill, Anthony J. and Chou,
Angela S. and Clarkson, Adele and Botling, Johan and Stalberg, Peter
L. H. and Skogseid, Britt M. and Robinson, Bruce G. and Sidhu, Stanley
B. and Clifton-Bligh, Roderick J.},
title = {The Glucocorticoid Receptor Is Overexpressed in Malignant Adrenocortical
Tumors},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {4591--4599},
number = {11},
month = nov,
abstract = {Context: Adrenocortical carcinoma (ACC) is a rare tumor with a poor
prognosis. The Weiss score is the most widely accepted method for
distinguishing an ACC from an adrenocortical adenoma (ACA); however,
in borderline cases, accurate diagnosis remains problematic. We recently
discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly
up-regulated in ACCs compared with ACAs in global gene expression
studies. Objective: Our objective was to study GR expression in adrenocortical
tumors (ACTs) and to assess its utility as an adjunct to the Weiss
score. Design: Microarray analysis, real-time quantitative RT-PCR
(qPCR), immunohistochemistry, Western blot, and direct sequencing
were performed. Results: Analysis of 28 ACTs by microarray and 49
ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared
with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the
presence of the GR{alpha} isoform in ACCs, and no mutations were
detected on direct sequencing. Immunohistochemistry for GR in an
overlapping cohort of ACTs demonstrated strongly positive nuclear
staining in 31 of 33 ACCs (94%), with negative staining in 40 of
41 ACAs (98%) (P < 0.001). This finding was validated in an external
cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive
nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001).
Conclusions: The immunohistochemical finding of nuclear GR staining
identified ACCs with high diagnostic accuracy. We propose that GR
immunohistochemistry may complement the Weiss score in the diagnosis
of ACC in cases that display borderline histology. The possibility
that GR is transcriptionally active in these tumors, and may therefore
be a therapeutic target, requires further study.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/11/4591}
}
@ARTICLE{Tada2011,
author = {Tada, Ko-ichi and Kawahara, Ko-ichi and Matsushita, Shigeto and Hashiguchi,
Teruto and Maruyama, Ikuro and Kanekura, Takuro},
title = {MK615, a Prunus mume Steb. Et Zucc (`Ume`) Extract, Attenuates the
Growth of A375 Melanoma Cells by Inhibiting the ERK1/2-Id-1 Pathway},
journal = {Phytotherapy Research},
year = {2011},
volume = {na},
pages = {n/a--n/a},
abstract = {The Japanese apricot, a commonly consumed food called ‘Ume’ in
Japan, has been used for a traditional Japanese medicine for centuries.
MK615, an extract of compounds from ‘Ume’, has strong antitumorigenic
and antiinflammatory effects including the induction of apoptosis
and autophagy, and inhibition of cytokine production mediated via
the inhibition of MAPKs signaling including ERK-1/2, JNK and p38MAPK.
The inhibitor of DNA binding 1 (Id-1), a basic helix-loop-helix (bHLH)
transcription factor family, is essential for DNA binding and the
transcriptional regulation of various proteins that play important
roles in the development, progression and invasion of tumors. In
melanoma, Id-1 is constitutively expressed in the late and early
stages, suggesting it as a therapeutic target in patients with melanoma.
This study reports that MK615 profoundly reduced both the mRNA- and
protein expression levels of Id-1 and inhibited cell growth in A375
melanoma cells. MK615 markedly inhibited the phosphorylation of ERK1/2,
which is associated with Id-1 protein expression in A375 cells. Id-1-specific
RNAi induced the death of A375 cells. Moreover, the expression of
Bcl-2 was decreased by both MK615 and Id-1-specific RNAi in A375
cells. The results suggest that MK615 is a potential therapeutic
agent for treating malignant melanoma. Copyright © 2011 John Wiley
& Sons, Ltd.},
doi = {10.1002/ptr.3645},
issn = {1099-1573},
keywords = {MK615, inhibitor of DNA binding 1 (Id-1), melanoma, ERK1/2},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/ptr.3645}
}
@ARTICLE{Tadin-Strapps2011,
author = {Tadin-Strapps, Marija and Peterson, Laurence B. and Cumiskey, Anne-Marie
and Rosa, Raymond L. and Mendoza, Vivienne Halili and Castro-Perez,
Jose and Puig, Oscar and Zhang, Liwen and Strapps, Walter R. and
Yendluri, Satyasri and Andrews, Lori and Pickering, Victoria and
Rice, Julie and Luo, Lily and Chen, Zhu and Tep, Samnang and Ason,
Brandon and Somers, Elizabeth Polizzi and Sachs, Alan B. and Bartz,
Steven R. and Tian, Jenny and Chin, Jayne and Hubbard, Brian K. and
Wong, Kenny K. and Mitnaul, Lyndon J.},
title = {siRNA-induced liver ApoB knockdown lowers serum LDL-cholesterol in
a mouse model with human-like serum lipids},
journal = {J. Lipid Res.},
year = {2011},
volume = {52},
pages = {1084--1097},
number = {6},
month = jun,
abstract = {Increased serum apolipoprotein (apo)B and associated LDL levels are
well-correlated with an increased risk of coronary disease. ApoE-/-
and low density lipoprotein receptor (LDLr)-/- mice have been extensively
used for studies of coronary atherosclerosis. These animals show
atherosclerotic lesions similar to those in humans, but their serum
lipids are low in apoB-containing LDL particles. We describe the
development of a new mouse model with a human-like lipid profile.
Ldlr CETP+/- hemizygous mice carry a single copy of the human CETP
transgene and a single copy of a LDL receptor mutation. To evaluate
the apoB pathways in this mouse model, we used novel short-interfering
RNAs (siRNA) formulated in lipid nanoparticles (LNP). ApoB siRNAs
induced up to 95% reduction of liver ApoB mRNA and serum apoB protein,
and a significant lowering of serum LDL in Ldlr CETP+/- mice. ApoB
targeting is specific and dose-dependent, and it shows lipid-lowering
effects for over three weeks. Although specific triglycerides (TG)
were affected by ApoB mRNA knockdown (KD) and the total plasma lipid
levels were decreased by 70%, the overall lipid distribution did
not change. Results presented here demonstrate a new mouse model
for investigating additional targets within the ApoB pathways using
the siRNA modality.},
comment = {10.1194/jlr.M012872},
url = {http://www.jlr.org/cgi/content/abstract/52/6/1084}
}
@ARTICLE{Tadiso2011a,
author = {Tadiso, Tariku and Krasnov, Aleksei and Skugor, Stanko and Afanasyev,
Sergey and Hordvik, Ivar and Nilsen, Frank},
title = {Gene expression analyses of immune responses in Atlantic salmon during
early stages of infection by salmon louse (Lepeophtheirus salmonis)
revealed bi-phasic responses coinciding with the copepod-chalimus
transition},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {141},
number = {1},
abstract = {BACKGROUND:The salmon louse (Lepeophtheirus salmonis Kroyer), an ectoparasitic
copepod with a complex life cycle causes significant losses in salmon
aquaculture. Pesticide treatments against the parasite raise environmental
concerns and their efficacy is gradually decreasing. Improvement
of fish resistance to lice, through biological control methods, needs
better understanding of the protective mechanisms. We used a 21 k
oligonucleotide microarray and RT-qPCR to examine the time-course
of immune gene expression changes in salmon skin, spleen, and head
kidney during the first 15 days after challenge, which encompassed
the copepod and chalimus stages of lice development.RESULTS:Large
scale and highly complex transcriptome responses were found already
one day after infection (dpi). Many genes showed bi-phasic expression
profiles with abrupt changes between 5 and 10 dpi (the copepod-chalimus
transitions); the greatest fluctuations (up- and down-regulation)
were seen in a large group of secretory splenic proteases with unknown
roles. Rapid sensing was witnessed with induction of genes involved
in innate immunity including lectins and enzymes of eicosanoid metabolism
in skin and acute phase proteins in spleen. Transient (1-5 dpi) increase
of T-cell receptor alpha, CD4-1, and possible regulators of lymphocyte
differentiation suggested recruitment of T-cells of unidentified
lineage to the skin. After 5 dpi the magnitude of transcriptomic
responses decreased markedly in skin. Up-regulation of matrix metalloproteinases
in all studied organs suggested establishment of a chronic inflammatory
status. Up-regulation of putative lymphocyte G0/G1 switch proteins
in spleen at 5 dpi, immunoglobulins at 15 dpi; and increase of IgM
and IgT transcripts in skin indicated an onset of adaptive humoral
immune responses, whereas MHCI appeared to be down-regulated.CONCLUSIONS:Atlantic
salmon develops rapid local and systemic reactions to L. salmonis,
which, however, do not result in substantial level of protection.
The dramatic changes observed after 5 dpi can be associated with
metamorphosis of copepod, immune modulation by the parasite, or transition
from innate to adaptive immune responses.},
doi = {10.1186/1471-2164-12-141},
issn = {1471-2164},
pubmedid = {21385383},
url = {http://www.biomedcentral.com/1471-2164/12/141}
}
@ARTICLE{Tadiso2011,
author = {Tadiso, Tariku Markos and Lie, Kai Kristoffer and Hordvik, Ivar},
title = {Molecular cloning of IgT from Atlantic salmon, and analysis of the
relative expression of [tau], [mu] and [delta] in different tissues},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {139},
pages = {17--26},
number = {1},
month = jan,
abstract = {In the present study, IgT genes of Atlantic salmon were cloned and
characterised. Analysis of our sequence data as well as ESTs reported
to the databases revealed three distinct IgT heavy chain sub-variants
in salmon, as opposed to two of IgM and IgD. The IgT sub-variants
in salmon are 76-80% identical to each other, and 75-82% identical
to the reported rainbow trout sequences, whereas the similarity to
the orthologous molecules in zebrafish, grass carp, mandarin fish,
and grouper is 25-41%. The heavy chains of both secreted and membrane
anchored forms of salmon IgT include four constant Ig domains, [tau]1-[tau]4.
This parallels the IgM heavy chains in elasmobranch fish and higher
vertebrates, but differs from IgM in teleost fish where the membrane
anchored form include only three constant Ig domains, [mu]1-[mu]3.
The similarity between [tau]1 and [mu]1 in salmon is relatively high
(52%) when compared to the remaining part of the molecules ([tau]2-[tau]4
and [mu]2-[mu]4 are 13-24% similar). To compare [tau], [mu] and [delta]
expressions in different tissues (head kidney, thymus, spleen, gill,
skin, hind gut, brain and muscle) of Atlantic salmon, RT-qPCR assays
were designed and evaluated. The analyses revealed that IgM transcripts
are most abundant (up to 200 times more than IgD) followed by IgT
(up to 20 times more than IgD) in most tissues. Highest expression
of IgM, IgT, and IgD was in head kidney and spleen.},
issn = {0165-2427},
keywords = {IgT, IgM, IgD, Atlantic salmon, Teleost},
url = {http://www.sciencedirect.com/science/article/pii/S0165242710002758}
}
@ARTICLE{Tadros2007,
author = {Tadros, Sherif F. and D'Souza, Mary and Zettel, Martha L. and Zhu,
XiaoXia and Lynch-Erhardt, Martha and Frisina, Robert D.},
title = {Serotonin 2B receptor: Upregulated with age and hearing loss in mouse
auditory system},
journal = {Neurobiology of Aging},
year = {2007},
volume = {28},
pages = {1112--1123},
number = {7},
month = jul,
abstract = {Serotonin (5-HT) is a monoamine neurotransmitter. Serotonin may modulate
afferent fiber discharges in the cochlea, inferior colliculus (IC)
and auditory cortex. Specific functions of serotonin are exerted
upon its interaction with specific receptors; one of those receptors
is the serotonin 2B receptor. The aim of this study was to investigate
the differences in gene expression of serotonin 2B receptors with
age in cochlea and IC, and the possible correlation between gene
expression and functional hearing measurements in CBA/CaJ mice. Immunohistochemical
examinations of protein expression of IC in mice of different age
groups were also performed. Gene expression results showed that serotonin
2B receptor gene was upregulated with age in both cochlea and IC.
A significant correlation between gene expression and functional
hearing results was established. Immunohistochemical protein expression
studies of IC showed more serotonin 2B receptor cells in old mice
relative to young adult mice, particularly in the external nucleus.
We conclude that serotonin 2B receptors may play a role in the pathogenesis
of age-related hearing loss.},
issn = {0197-4580},
keywords = {Presbycusis, Cochlea, Inferior colliculus, Gene microarray, Immunohistochemistry,
Otoacoustic emissions},
url = {http://www.sciencedirect.com/science/article/B6T09-4KBDW86-2/2/ac673910c576124d30d11d70eed9b3e5}
}
@ARTICLE{Tadros2007a,
author = {Tadros, Sherif F. and D'Souza, Mary and Zettel, Martha L. and Zhu,
XiaoXia and Waxmonsky, Nicole C. and Frisina, Robert D.},
title = {Glutamate-related gene expression changes with age in the mouse auditory
midbrain},
journal = {Brain Research},
year = {2007},
volume = {1127},
pages = {1--9},
month = jan,
abstract = {Glutamate is the main excitatory neurotransmitter in both the peripheral
and central auditory systems. Changes of glutamate and glutamate-related
genes with age may be an important factor in the pathogenesis of
age-related hearing loss--presbycusis. In this study, changes in
glutamate-related mRNA gene expression in the CBA mouse inferior
colliculus with age and hearing loss were examined and correlations
were sought between these changes and functional hearing measures,
such as the auditory brainstem response (ABR) and distortion product
otoacoustic emissions (DPOAEs). Gene expression of 68 glutamate-related
genes was investigated using both genechip microarray and real-time
PCR (qPCR) molecular techniques for four different age/hearing loss
CBA mouse subject groups. Two genes showed consistent differences
between groups for both the genechip and qPCR. Pyrroline-5-carboxylate
synthetase enzyme (Pycs) showed down-regulation with age and a high-affinity
glutamate transporter (Slc1a3) showed up-regulation with age and
hearing loss. Since Pycs plays a role in converting glutamate to
proline, its deficiency in old age may lead to both glutamate increases
and proline deficiencies in the auditory midbrain, playing a role
in the subsequent inducement of glutamate toxicity and loss of proline
neuroprotective effects. The up-regulation of Slc1a3 gene expression
may reflect a cellular compensatory mechanism to protect against
age-related glutamate or calcium excitoxicity.},
issn = {0006-8993},
keywords = {Gene expression, Functional hearing, Presbycusis, Inferior colliculus,
Aging, Real-time PCR, Auditory brainstem response, Distortion-product
otoacoustic emissions, ABR, DPOAE},
url = {http://www.sciencedirect.com/science/article/B6SYR-4MC71PM-4/2/aed983d84aed8b34be880bf834bef8ff}
}
@ARTICLE{Tagaya2009,
author = {Tagaya, Mitsuhiro and Oka, Michiko and Ueda, Makoto and Takagaki,
Kazuchika and Tanaka, Mitsushi and Ohgi, Tadaaki and Yano, Junichi},
title = {Eviprostat suppresses proinflammatory gene expression in the prostate
of rats with partial bladder-outlet obstruction: A genome-wide DNA
microarray analysis},
journal = {Cytokine},
year = {2009},
volume = {47},
pages = {185--193},
number = {3},
month = sep,
abstract = {Prostatic inflammation plays a role in the progression of benign prostatic
hyperplasia (BPH). Eviprostat is an antioxidant, antiinflammatory
phytotherapeutic agent widely used to treat lower urinary tract symptoms
in BPH. Because Eviprostat is a mixture of compounds from multiple
natural sources, however, its mechanism of action has been difficult
to investigate. Here, we describe the use of oligonucleotide microarrays
to investigate changes in gene expression in the prostate of rats
with surgically induced partial bladder-outlet obstruction and the
effect of Eviprostat on those changes. Several dozen proinflammatory
genes were activated in obstructed rats, including cytokine, arachidonic
acid cascade enzyme, Toll-like receptor (TLR), and transcription
factor genes, and their expression was suppressed by Eviprostat.
Pathway analysis revealed that several proinflammatory pathways were
activated, including cytokine and TLR signaling pathways. The differential
expression of selected genes was verified by real-time reverse-transcriptase
polymerase chain reaction. Our findings suggest that prostate inflammation
in our rat model of partial bladder-outlet obstruction is related
to the increased expression of nuclear factor [kappa]B (NF-[kappa]B)
and the induction of proinflammatory cytokines, and that Eviprostat
suppresses their expression at the transcriptional level. The prostate
inflammation seen in BPH and the clinical benefits of Eviprostat
may be similarly explained.},
issn = {1043-4666},
keywords = {Eviprostat, Bladder-outlet obstruction, Benign prostatic hyperplasia,
Microarray, Pathway analysis},
url = {http://www.sciencedirect.com/science/article/B6WDF-4WSR0RK-2/2/7e270761ad868f7248fe3e62aa9301ee}
}
@ARTICLE{Taggart2008,
author = {Taggart, J. B. and Bron, J. E. and Martin, S. A. M. and Seear, P.
J. and Høyheim, B. and Talbot, R. and Carmichael, S. N. and Villeneuve,
L. A. N. and Sweeney, G. E. and Houlihan, D. F. and Secombes, C.
J. and Tocher, D. R. and Teale, A. J.},
title = {A description of the origins, design and performance of the TRAITS–SGP
Atlantic salmon Salmo salar L. cDNA microarray},
journal = {Journal of Fish Biology},
year = {2008},
volume = {72},
pages = {2071--2094},
number = {9},
abstract = {The origins, design, fabrication and performance of an Atlantic salmon
microarray are described. The microarray comprises 16 950 Atlantic
salmon-derived cDNA features, printed in duplicate and mostly sourced
from pre-existing expressed sequence tag (EST) collections [SALGENE
and salmon genome project (SGP)] but also supplemented with cDNAs
from suppression subtractive hybridization libraries and candidate
genes involved in immune response, protein catabolism, lipid metabolism
and the parr–smolt transformation. A preliminary analysis of a
dietary lipid experiment identified a number of genes known to be
involved in lipid metabolism. Significant fold change differences
(as low as 1·2×) were apparent from the microarray analysis and
were confirmed by quantitative real-time polymerase chain reaction
analysis. The study also highlighted the potential for obtaining
artefactual expression patterns as a result of cross-hybridization
of similar transcripts. Examination of the robustness and sensitivity
of the experimental design employed demonstrated the greater importance
of biological replication over technical (dye flip) replication for
identification of a limited number of key genes in the studied system.
The TRAITS (TRanscriptome Analysis of Important Traits of Salmon)–salmon
genome project microarray has been proven, in a number of studies,
to be a powerful tool for the study of key traits of Atlantic salmon
biology. It is now available for use by researchers in the wider
scientific community.},
issn = {1095-8649},
keywords = {Atlantic salmon, DNA microarray, gene expression, immune response,
lipid metabolism, smoltification},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1095-8649.2008.01876.x}
}
@ARTICLE{Tagliafico2004,
author = {Tagliafico, Enrico and Brunelli, Silvia and Bergamaschi, Anna and
De Angelis, Luciana and Scardigli, Raffaella and Galli, Daniela and
Battini, Renata and Bianco, Paolo and Ferrari, Sergio and Cossu,
Giulio and Ferrari, Stefano},
title = {TGF{beta}/BMP activate the smooth muscle/bone differentiation programs
in mesoangioblasts},
journal = {J. Cell Sci.},
year = {2004},
volume = {117},
pages = {4377--4388},
number = {19},
month = sep,
abstract = {Mesoangioblasts are vessel-derived stem cells that can be induced
to differentiate into different cell types of the mesoderm such as
muscle and bone. The gene expression profile of four clonal derived
lines of mesoangioblasts was determined by DNA micro-array analysis:
it was similar in the four lines but different from 10T1/2 embryonic
fibroblasts, used as comparison. Many known genes expressed by mesoangioblasts
belong to response pathways to developmental signalling molecules,
such as Wnt or TGF{beta}/BMP. Interestingly, mesoangioblasts express
receptors of the TGF{beta}/BMP family and several Smads and, accordingly,
differentiate very efficiently into smooth muscle cells in response
to TGF{beta} and into osteoblasts in response to BMP. In addition,
insulin signalling promotes adipogenic differentiation, possibly
through the activation of IGF-R. Several Wnts and Frizzled, Dishevelled
and Tcfs are expressed, suggesting the existence of an autocrine
loop for proliferation and indeed, forced expression of Frzb-1 inhibits
cell division. Mesoangioblasts also express many neuro-ectodermal
genes and yet undergo only abortive neurogenesis, even after forced
expression of neurogenin 1 or 2, MASH or NeuroD. Finally, mesoangioblasts
express several pro-inflammatory genes, cytokines and cytokine receptors,
which may explain their ability to be recruited by tissue inflammation.
Our data define a unique phenotype for mesoangioblasts, explain several
of their biological features and set the basis for future functional
studies on the role of these cells in tissue histogenesis and repair.},
url = {http://jcs.biologists.org/cgi/content/abstract/117/19/4377}
}
@ARTICLE{Tahira2011,
author = {Tahira, Ana and Kubrusly, Marcia and Faria, Michele and Dazzani,
Bianca and Fonseca, Rogerio and Maracaja-Coutinho, Vinicius and Verjovski-Almeida,
Sergio and Machado, Marcel and Reis, Eduardo},
title = {Long noncoding intronic RNAs are differentially expressed in primary
and metastatic pancreatic cancer},
journal = {Molecular Cancer},
year = {2011},
volume = {10},
pages = {141},
number = {1},
abstract = {BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is known by its
aggressiveness and lack of effective therapeutic options. Thus, improvement
in current knowledge of molecular changes associated with pancreatic
cancer is urgently needed to explore novel venues of diagnostics
and treatment of this dismal disease. While there is mounting evidence
that long noncoding RNAs (lncRNAs) transcribed from intronic and
intergenic regions of the human genome may play different roles in
the regulation of gene expression in normal and cancer cells, their
expression pattern and biological relevance in pancreatic cancer
is currently unknown. In the present work we investigated the relative
abundance of a collection of lncRNAs in patients' pancreatic tissue
samples aiming at identifying gene expression profiles correlated
to pancreatic cancer and metastasis.METHODS:Custom 3,355-element
spotted cDNA microarray interrogating protein-coding genes and putative
lncRNA were used to obtain expression profiles from 38 clinical samples
of tumor and non-tumor pancreatic tissues. Bioinformatics analyses
were performed to characterize structure and conservation of lncRNAs
expressed in pancreatic tissues, as well as to identify expression
signatures correlated to tissue histology. Strand-specific reverse
transcription followed by PCR and qRT-PCR were employed to determine
strandedness of lncRNAs and to validate microarray results, respectively.RESULTS:We
show that subsets of intronic/intergenic lncRNAs are expressed across
tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated
chromatin marks and over-representation of conserved DNA elements
and stable secondary structure predictions suggest that these transcripts
are generated from independent transcriptional units and that at
least a fraction is under evolutionary selection, and thus potentially
functional.Statistically significant expression signatures comprising
protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic
cancer metastasis were identified. Interestingly, loci harboring
intronic lncRNAs differentially expressed in PDAC metastases were
enriched in genes associated to the MAPK pathway. Orientation-specific
RT-PCR documented that intronic transcripts are expressed in sense,
antisense or both orientations relative to protein-coding mRNAs.
Differential expression of a subset of intronic lncRNAs (PPP3CB,
MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time
PCR.CONCLUSION:Our findings reveal sets of intronic lncRNAs expressed
in pancreatic tissues whose abundance is correlated to PDAC or metastasis,
thus pointing to the potential relevance of this class of transcripts
in biological processes related to malignant transformation and metastasis
in pancreatic cancer.},
doi = {10.1186/1476-4598-10-141},
issn = {1476-4598},
pubmedid = {22078386},
url = {http://www.molecular-cancer.com/content/10/1/141}
}
@ARTICLE{Tahoe2004,
author = {Tahoe, Nuzha M. A. and Mokhtarzadeh, Ali and Curtsinger, James W.},
title = {Age-Related RNA Decline in Adult Drosophila melanogaster},
journal = {J Gerontol A Biol Sci Med Sci},
year = {2004},
volume = {59},
pages = {B896--901},
number = {9},
month = sep,
abstract = {We investigated the correlation between age and total RNA levels in
long-lived and control lines of Drosophila melanogaster. Total RNA
was extracted at 10 ages from 1-63 days posteclosion from 3 inbred
lines, with replication. Three different methods of RNA quantitation
gave highly correlated estimates. Total RNA declined substantially
with age, exhibiting a dramatic drop in the first few days of adult
life. We find no evidence for a causal relationship between adult
longevity and total RNA levels, since long-lived and control lines
exhibited similar patterns of age-related RNA decline. These observations
suggest that the dramatic decline in total RNA that occurs early
in adult life does not explain the twofold differences in life span
between lines. The pattern of age-specific decline coincides with
published observations on age-specific metabolic rates, and suggests
that 14-day-old flies are functionally senescent.},
url = {http://biomedgerontology.oxfordjournals.org/cgi/content/abstract/59/9/B896}
}
@ARTICLE{Tai2007,
author = {Tai, Siew Leng and Daran-Lapujade, Pascale and Luttik, Marijke A.
H. and Walsh, Michael C. and Diderich, Jasper A. and Krijger, Gerard
C. and van Gulik, Walter M. and Pronk, Jack T. and Daran, Jean-Marc},
title = {Control of the Glycolytic Flux in Saccharomyces cerevisiae Grown
at Low Temperature: A MULTI-LEVEL ANALYSIS IN ANAEROBIC CHEMOSTAT
CULTURES},
journal = {J. Biol. Chem.},
year = {2007},
volume = {282},
pages = {10243--10251},
number = {14},
month = apr,
abstract = {Growth temperature has a profound impact on the kinetic properties
of enzymes in microbial metabolic networks. Activities of glycolytic
enzymes in Saccharomyces cerevisiae were up to 7.5-fold lower when
assayed at 12 {degrees}C than at 30 {degrees}C. Nevertheless, the
in vivo glycolytic flux in chemostat cultures (dilution rate: 0.03
h-1) grown at these two temperatures was essentially the same. To
investigate how yeast maintained a constant glycolytic flux despite
the kinetic challenge imposed by a lower growth temperature, a systems
approach was applied that involved metabolic flux analysis, transcript
analysis, enzyme activity assays, and metabolite analysis. Expression
of hexose-transporter genes was affected by the growth temperature,
as indicated by differential transcription of five HXT genes and
changed zero trans-influx kinetics of [14C]glucose transport. No
such significant changes in gene expression were observed for any
of the glycolytic enzymes. Fermentative capacity (assayed off-line
at 30 {degrees}C), which was 2-fold higher in cells grown at 12 {degrees}C,
was therefore probably controlled predominantly by glucose transport.
Massive differences in the intracellular concentrations of nucleotides
(resulting in an increased adenylate energy charge at low temperature)
and glycolytic intermediates indicated a dominant role of metabolic
control as opposed to gene expression in the adaptation of glycolytic
enzyme activity to different temperatures. In evolutionary terms,
this predominant reliance on metabolic control of a central pathway,
which represents a significant fraction of the cellular protein of
the organism, may be advantageous to limit the need for protein synthesis
and degradation during adaptation to diurnal temperature cycles.},
url = {http://www.jbc.org/cgi/content/abstract/282/14/10243}
}
@ARTICLE{Tai2007a,
author = {Tai, Siew Leng and Daran-Lapujade, Pascale and Walsh, Michael C.
and Pronk, Jack T. and Daran, Jean-Marc},
title = {Acclimation of Saccharomyces cerevisiae to Low Temperature: A Chemostat-based
Transcriptome Analysis},
journal = {Mol. Biol. Cell},
year = {2007},
volume = {18},
pages = {5100--5112},
number = {12},
month = dec,
abstract = {Effects of suboptimal temperatures on transcriptional regulation in
yeast have been extensively studied in batch cultures. To eliminate
indirect effects of specific growth rates that are inherent to batch-cultivation
studies, genome-wide transcriptional responses to low temperatures
were analyzed in steady-state chemostats, grown at a fixed specific
growth rate (0.03 h-1). Although in vivo metabolic fluxes were essentially
the same in cultures grown at 12 and at 30{degrees}C, concentrations
of the growth-limiting nutrients (glucose or ammonia) were higher
at 12{degrees}C. This difference was reflected by transcript levels
of genes that encode transporters for the growth-limiting nutrients.
Several transcriptional responses to low temperature occurred under
both nutrient-limitation regimes. Increased transcription of ribosome-biogenesis
genes emphasized the importance of adapting protein-synthesis capacity
to low temperature. In contrast to observations in cold-shock and
batch-culture studies, transcript levels of environmental stress
response genes were reduced at 12{degrees}C. Transcription of trehalose-biosynthesis
genes and intracellular trehalose levels indicated that, in contrast
to its role in cold-shock adaptation, trehalose is not involved in
steady-state low-temperature adaptation. Comparison of the chemostat-based
transcriptome data with literature data revealed large differences
between transcriptional reprogramming during long-term low-temperature
acclimation and the transcriptional responses to a rapid transition
to low temperature.},
url = {http://www.molbiolcell.org/cgi/content/abstract/18/12/5100}
}
@ARTICLE{Taildeman2010,
author = {Taildeman, Jasmien and Demetter, Pieter and Rottiers, Isabelle and
Holtappels, Gabriele and Bachert, Claus and Cuvelier, Claude A and
Pérez-Novo, Claudina A},
title = {Identification of the nasal mucosa as a new target for leptin action},
journal = {Histopathology},
year = {2010},
volume = {56},
pages = {789--798},
number = {6},
abstract = {Taildeman J, Demetter P, Rottiers I, Holtappels G, Bachert C, Cuvelier
C A & Pérez-Novo C A (2010) Histopathology 56, 789–798 Identification
of the nasal mucosa as a new target for leptin action Aims:  Leptin
is a key molecule in the regulation of energy homeostasis. Furthermore,
several studies indicate that leptin also plays a pivotal role in
immune and inflammatory responses. The aim of this study was to examine
systemic and local nasal leptin and leptin receptor expression in
patients with nasal polyposis and healthy controls. Methods and results: 
Serum leptin and soluble leptin receptor levels were examined by
enzyme-linked immunosorbent assay (ELISA). The presence of leptin
and leptin receptor mRNA was investigated using reverse transcriptase-polymerase
chain reaction (RT-PCR), and tissue leptin and leptin receptor protein
expression was analysed by immunohistochemistry and ELISA. Serum
levels of biologically active leptin were significantly elevated
in patients with nasal polyps compared with control subjects. These
serum leptin levels were strongly correlated with the levels found
in tissue in both study groups, although leptin was not significantly
elevated in nasal polyp tissue. Using RT-PCR, we showed that both
leptin and its receptors were produced in nasal mucosa. Finally,
immunohistochemistry showed that leptin and leptin receptor protein
were expressed in several cells of the normal and inflamed nasal
mucosa. Conclusions:  Leptin receptors and their biological ligand
leptin are expressed in the nasal mucosa, suggesting a possible role
in upper airway immunology.},
issn = {1365-2559},
keywords = {leptin, leptin receptor, nasal polyps},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2559.2010.03552.x}
}
@ARTICLE{Taira2012,
author = {Junsei Taira and Wakana Ohmine and Takayuki Ogi and Hitoshi Nanbu
and Katsuhiro Ueda},
title = {Suppression of nitric oxide production on LPS/IFN-γ -stimulated
RAW264.7 macrophages by a novel catechin, pilosanol N, from Agrimonia
pilosa Ledeb},
journal = {Bioorganic \& Medicinal Chemistry Letters},
year = {2012},
pages = { - },
number = {0},
abstract = {A novel catechin, pilosanol N (1), was isolated from Agrimonia pilosa
Ledeb and its structure was determined by 1H, 13C-NMR and HRESI-MS
analyses. Compound 1 inhibited nitric oxide (NO) production in LPS/IFN-γ
-induced RAW264.7 macrophages, and then the iNOS gene expression
and its protein production with LPS/IFN-γ treatment cells were also
suppressed in the presence of 1. In addition, compound 1 scavenged
NO or nitrogen radicals generated from NOR3 (4-ethyl-2-hydroxyamino-5-nitro-3-hexenamide)
as an NO donor. These results indicated that pilosanol N can decrease
the level of NO through a mechanism that involved both a decrease
in the NO production and NO scavenging.},
doi = {10.1016/j.bmcl.2011.12.086},
issn = {0960-894X},
keywords = {Nitric oxide},
url = {http://www.sciencedirect.com/science/article/pii/S0960894X11017677?v=s5}
}
@ARTICLE{Tajeddine2005,
author = {Tajeddine, Nicolas and Gala, Jean-Luc and Louis, Magali and Van Schoor,
Monique and Tombal, Bertrand and Gailly, Philippe},
title = {Tumor-Associated Antigen Preferentially Expressed Antigen of Melanoma
(PRAME) Induces Caspase-Independent Cell Death In vitro and Reduces
Tumorigenicity In vivo},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {7348--7355},
number = {16},
month = aug,
abstract = {Preferentially expressed antigen of melanoma (PRAME) is expressed
in a wide variety of tumors, but in contrast with most other tumor
associated antigens, it is also expressed in leukemias. The physiologic
role of PRAME remains elusive. Interestingly, PRAME expression is
correlated with a favorable prognosis in childhood acute leukemias.
Moreover, a high expression of PRAME seems to be predominantly found
in acute leukemias carrying a favorable prognosis. On these clinical
observations, we assumed that PRAME could be involved in the regulation
of cell death or cell cycle. In this study, we show that transient
overexpression of PRAME induces a caspase-independent cell death
in cultured cell lines (CHO-K1 and HeLa). Cells stably transfected
with PRAME also exhibit a decreased proliferation rate due, at least
partially, to an elevated basal rate of cell death. Immunocytochemistry
of a FLAG-tagged PRAME, in vivo imaging of an enhanced green fluorescent
protein-tagged PRAME, and Western blotting after cell fractionation
reveal a nuclear localization of the protein. Using a microarray-based
approach, we show that KG-1 leukemic cells stably transfected with
PRAME present a significant decrease of expression of the heat-shock
protein Hsp27, the cyclin-dependent kinase inhibitor p21, and the
calcium-binding protein S100A4. The expression of these three proteins
is known to inhibit apoptosis and has been associated with an unfavorable
prognosis in a series of cancers. Finally, repression of PRAME expression
by a short interfering RNA strategy increases tumorigenicity of K562
leukemic cells in nude mice. We suggest that all these observations
might explain the favorable prognosis of the leukemias expressing
high levels of PRAME.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/16/7348}
}
@ARTICLE{Tajes2010,
author = {Tajes, M. and Gutierrez-Cuesta, J. and Folch, J. and Ortuño-Sahagun,
D. and Verdaguer, E. and Jiménez, A. and Junyent, F. and Lau, A.
and Camins, A. and Pallàs, M.},
title = {Neuroprotective role of intermittent fasting in senescence-accelerated
mice P8 (SAMP8)},
journal = {Experimental Gerontology},
year = {2010},
volume = {45},
pages = {702--710},
number = {9},
month = sep,
abstract = {Dietary interventions have been proposed as a way to increase lifespan
and improve health. The senescence-accelerated prone 8 (SAMP8) mice
have a shorter lifespan and show alterations in the central nervous
system. Moreover, this mouse strain shows decreased sirtuin 1 protein
expression and elevated expression of the acetylated targets NF[kappa]B
and FoxO1, which are implicated in transcriptional control of key
genes in cell proliferation and cell survival, in reference to control
strain, SAMR1. After eight weeks of intermittent fasting, sirtuin
1 protein expression was recovered in SAMP8. This recovery was accompanied
by a reduction in the two acetylated targets. Furthermore, SAMP8
showed a lower protein expression of BDNF and HSP70 while intermittent
fasting re-established normal values. The activation of JNK and FoxO1
was also reduced in SAMP8 mice subjected to an IF regimen, compared
with control SAMP8. Our findings provide new insights into the participation
of sirtuin 1 in ageing and point to a potential novel application
of this enzyme to prevent frailty due to ageing processes in the
brain.},
issn = {0531-5565},
keywords = {Ageing, Neurodegeneration, NF[kappa]B, ADAM10, BDNF, Sirtuin 1},
url = {http://www.sciencedirect.com/science/article/B6T6J-5025V9N-1/2/da0ed0a0929699f536ee7783172f5a75}
}
@ARTICLE{Tajouri2003,
author = {Tajouri, Lotti and Mellick, Albert S. and Ashton, Kevin J. and Tannenberg,
Anthony E. G. and Nagra, Rashed M. and Tourtellotte, Wallace W. and
Griffiths, Lyn R.},
title = {Quantitative and qualitative changes in gene expression patterns
characterize the activity of plaques in multiple sclerosis},
journal = {Molecular Brain Research},
year = {2003},
volume = {119},
pages = {170--183},
number = {2},
month = nov,
abstract = {Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS
with both genetic and environmental contributing factors. Clinical
symptoms are broadly characterized by initial onset, and progressive
debilitating neurological impairment. In this study, RNA from MS
chronic active and MS acute lesions was extracted, and compared with
patient matched normal white matter by fluorescent cDNA microarray
hybridization analysis. This resulted in the identification of 139
genes that were differentially regulated in MS plaque tissue compared
to normal tissue. Of these, 69 genes showed a common pattern of expression
in the chronic active and acute plaque tissues investigated (Pvalue<0.0001,
[rho]=0.73, by Spearman's [rho] analysis); while 70 transcripts were
uniquely differentially expressed (>=1.5-fold) in either acute or
chronic active tissues. These results included known markers of MS
such as the myelin basic protein (MBP) and glutathione S-transferase
(GST) M1, nerve growth factors, such as nerve injury-induced protein
1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5)
and X-linked genes such as the ribosomal protein, RPS4X. Primers
were then designed for seven array-selected genes, including transferrin
(TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1),
GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and
tubulin [beta]-5 (TBB5), and real time quantitative (Q)-PCR analysis
was performed. The results of comparative Q-PCR analysis correlated
significantly with those obtained by array analysis (r=0.75, Pvalue<0.01,
by Pearson's bivariate correlation). Both chronic active and acute
plaques shared the majority of factors identified suggesting that
quantitative, rather than gross qualitative differences in gene expression
pattern may define the progression from acute to chronic active plaques
in MS.},
issn = {0169-328X},
keywords = {Multiple sclerosis, Plaque, Chronic active, Acute, cDNA microarray,
Quantitative PCR analysis},
url = {http://www.sciencedirect.com/science/article/B6T07-49W36KG-1/2/8661b5bbc7f0dd437e9afd5a29d26319}
}
@ARTICLE{Takacs2011,
author = {Takacs, Lili and Toth, Eniko and Losonczy, Gergely and Szanto, Attila
and Bahr-Ivacevic, Tomi and Benes, Vladimir and Berta, Andras and
Vereb, Gyorgy},
title = {Differentially Expressed Genes Associated with Human Limbal Epithelial
Phenotypes: New Molecules That Potentially Facilitate Selection of
Stem Cell-Enriched Populations},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {1252--1260},
number = {3},
month = mar,
abstract = {Purpose.The aim of this study was to identify differentially expressed
genes in the human limbal epithelium by microarray analysis. Methods.Total
RNA isolates of human limbal and central corneal epithelia were used
after transcription for hybridization on whole human genome expression
microarrays. A set of differentially expressed genes detected by
both microarrays was established. In the case of eight selected molecules,
microarray results were confirmed by qRT-PCR, and protein expression
in the cornea was examined by confocal immunofluorescence microscopy.
Colocalization with the putative stem cell marker C/EBP{delta} was
also examined. Results.The authors established a database of 126
limbal overexpressed genes. qRT-PCR confirmed microarray results
in all examined cases (SPON1, IFITM1, ITM2A, PHLDA1, CXCR4, FZD7,
DCT, DKK4). Limbal localization of the protein product of SPON1,
IFITM1, ITM2A, CXCR4, and DKK4 was shown with confocal immunofluorescence
microscopy. SPON1, IFITM1, and ITM2A signals mostly colocalized with
C/EBP{delta}-positive putative resting limbal stem cells. Conclusions.By
detecting several new differentially expressed genes in the human
corneal limbus, this study further expands current knowledge on the
molecular signature of limbal epithelial stem cells. Plasma membrane
localization of IFITM1 and ITM2A suggests their potential usefulness
as targets to select stem cell-enriched populations from the limbal
epithelium.},
comment = {10.1167/iovs.10-5242},
url = {http://www.iovs.org/cgi/content/abstract/52/3/1252}
}
@ARTICLE{Takada2004,
author = {Takada, Kazuki and Arefayene, Million and Desta, Zeruesenay and Yarboro,
Cheryl H. and Boumpas, Dimitrios T. and Balow, James E. and Flockhart,
David A. and Illei, Gabor G.},
title = {Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical
response to pulse cyclophosphamide in lupus nephritis},
journal = {Arthritis \& Rheumatism},
year = {2004},
volume = {50},
pages = {2202--2210},
number = {7},
abstract = {Abstract 10.1002/art.20338.abs Objective Pulse cyclophosphamide is
the treatment of choice for severe lupus nephritis. However, not
all patients respond to this therapy, and gonadal toxicity is of
particular concern. Cyclophosphamide is a prodrug that requires activation
by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort
study to test whether genetic polymorphisms of these enzymes are
associated with the toxicity of, and clinical response to, cyclophosphamide
in patients with lupus nephritis. Methods Sixty-two patients with
proliferative lupus nephritis treated with cyclophosphamide were
genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5.
We examined the association between these genotypes and the following
clinical end points: development of premature ovarian failure, end-stage
renal disease (ESRD), doubling of serum creatinine level, and achievement
of complete renal response. Results The observed frequencies of the
variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were
12.1%, 25.0%, 4.0%, and 75.8%, respectively. Patients who were either
heterozygous or homozygous for CYP2C19*2 had a significantly lower
risk of developing premature ovarian failure (relative risk 0.10;
95% confidence interval 0.02–0.52), after adjustment for age and
total number of cyclophosphamide pulses received. In a survival analysis,
patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had
a higher probability of reaching ESRD (P = 0.0005) and of doubling
the creatinine level (P = 0.0005) as well as a trend toward a lower
probability of achieving a complete renal response (P = 0.051). Conclusion
Determination of selected cytochrome P450 enzyme genotypes may be
valuable for predicting the risk of premature ovarian failure in
lupus nephritis patients treated with cyclophosphamide. The association
of these genotypes with renal response needs further validation.},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.20338}
}
@ARTICLE{Takahara2009,
author = {Takahara, Hiroyuki and Dolf, Andreas and Endl, Elmar and O’Connell,
Richard},
title = {Flow cytometric purification of Colletotrichum higginsianum biotrophic
hyphae from Arabidopsis leaves for stage-specific transcriptome analysis},
journal = {The Plant Journal},
year = {2009},
volume = {59},
pages = {672--683},
number = {4},
abstract = {Summary Generation of stage-specific cDNA libraries is a powerful
approach to identify pathogen genes that are differentially expressed
during plant infection. Biotrophic pathogens develop specialized
infection structures inside living plant cells, but sampling the
transcriptome of these structures is problematic due to the low ratio
of fungal to plant RNA, and the lack of efficient methods to isolate
them from infected plants. Here we established a method, based on
fluorescence-activated cell sorting (FACS), to purify the intracellular
biotrophic hyphae of Colletotrichum higginsianum from homogenates
of infected Arabidopsis leaves. Specific selection of viable hyphae
using a fluorescent vital marker provided intact RNA for cDNA library
construction. Pilot-scale sequencing showed that the library was
enriched with plant-induced and pathogenicity-related fungal genes,
including some encoding small, soluble secreted proteins that represent
candidate fungal effectors. The high purity of the hyphae (94%) prevented
contamination of the library by sequences derived from host cells
or other fungal cell types. RT-PCR confirmed that genes identified
in the FACS-purified hyphae were also expressed in planta. The method
has wide applicability for isolating the infection structures of
other plant pathogens, and will facilitate cell-specific transcriptome
analysis via deep sequencing and microarray hybridization, as well
as proteomic analyses.},
issn = {1365-313X},
keywords = {fluorescence-activated cell sorting (FACS), flow cytometry, biotrophy,
expressed sequence tags (ESTs), fungal effectors, Colletotrichum
higginsianum},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2009.03896.x}
}
@ARTICLE{Takahashi2011,
author = {Takahashi, Hirokazu and Saika, Hiroaki and Matsumura, Hideo and Nagamura,
Yoshiaki and Tsutsumi, Nobuhiro and Nishizawa, Naoko K. and Nakazono,
Mikio},
title = {Cell division and cell elongation in the coleoptile of rice alcohol
dehydrogenase 1-deficient mutant are reduced under complete submergence},
journal = {Ann. Bot.},
year = {2011},
volume = {108},
pages = {253-261},
number = {2},
abstract = {Background and AimsWhen rice seeds germinate under complete submergence,
only the coleoptile elongates efficiently. It has been reported previously
that coleoptile elongation is reduced in the rice alcohol dehydrogenase
1 (ADH1)-deficient mutant, reduced adh activity (rad). The aim of
this study was to elucidate how expressions of genes responsible
for coleoptile elongation are affected by the ADH1 deficiency in
the rad mutant under submergence. MethodsTo identify genes whose
expressions are changed in the rad coleoptile at an early stage in
germination (i.e. 1 d after imbibition), coleoptiles of the rad mutant
and its wild type (WT) were isolated by laser microdissection, and
their mRNA levels were examined with a microarray. Key ResultsThe
microarray analysis identified 431 genes whose transcript levels
were different between rad and WT. Interestingly, among the down-regulated
genes in the rad coleoptile, 17{middle dot}5 % were cell division-related
genes and 5{middle dot}1 % were cell elongation-related genes. It
was found that cell division started at 1 d after imbibition and
then gradually ceased, whereas in the WT coleoptile cell elongation
started between 1 d and 2 d after imbibition and then continued.
However, neither cell division nor cell elongation actively occurred
in the rad coleoptile, in which the amounts of ATP were reduced.
ConclusionsThese results indicate that cell division, as well as
cell elongation, occur during coleoptile elongation in rice under
complete submergence, and that the reduced ATP levels caused by the
ADH1 deficiency repress both of them, thereby impairing coleoptile
elongation in the rad mutant under submerged conditions.},
doi = {10.1093/aob/mcr137},
eprint = {http://aob.oxfordjournals.org/cgi/reprint/108/2/253.pdf},
url = {http://aob.oxfordjournals.org/cgi/content/abstract/108/2/253}
}
@ARTICLE{Takahashi2009,
author = {Takahashi, Hideyuki and Takahara, Kentaro and Hashida, Shin-nosuke
and Hirabayashi, Takayuki and Fujimori, Tamaki and Kawai-Yamada,
Maki and Yamaya, Tomoyuki and Yanagisawa, Shuichi and Uchimiya, Hirofumi},
title = {Pleiotropic Modulation of Carbon and Nitrogen Metabolism in Arabidopsis
Plants Overexpressing the NAD kinase2 Gene},
journal = {Plant Physiology},
year = {2009},
volume = {151},
pages = {100--113},
number = {1},
month = sep,
abstract = {Nicotinamide nucleotides (NAD and NADP) are important cofactors in
many metabolic processes in living organisms. In this study, we analyzed
transgenic Arabidopsis (Arabidopsis thaliana) plants that overexpress
NAD kinase2 (NADK2), an enzyme that catalyzes the synthesis of NADP
from NAD in chloroplasts, to investigate the impacts of altering
NADP level on plant metabolism. Metabolite profiling revealed that
NADP(H) concentrations were proportional to NADK activity in NADK2
overexpressors and in the nadk2 mutant. Several metabolites associated
with the Calvin cycle were also higher in the overexpressors, accompanied
by an increase in overall Rubisco activity. Furthermore, enhanced
NADP(H) production due to NADK2 overexpression increased nitrogen
assimilation. Glutamine and glutamate concentrations, as well as
some other amino acids, were higher in the overexpressors. These
results indicate that overexpression of NADK2 either directly or
indirectly stimulates carbon and nitrogen assimilation in Arabidopsis
under restricted conditions. Importantly, since neither up-regulation
nor down-regulation of NADK2 activity affected the sum amount of
NAD and NADP or the redox state, the absolute level of NADP and/or
the NADP/NAD ratio likely plays a key role in regulating plant metabolism.},
url = {http://www.plantphysiol.org/cgi/content/abstract/151/1/100}
}
@ARTICLE{Takahashi2010,
author = {Takahashi, Makoto and Hayashi, Hiroshi and Watanabe, Yuichiro and
Sawamura, Kazushi and Fukui, Naoki and Watanabe, Junzo and Kitajima,
Tsuyoshi and Yamanouchi, Yoshio and Iwata, Nakao and Mizukami, Katsuyoshi
and Hori, Takafumi and Shimoda, Kazutaka and Ujike, Hiroshi and Ozaki,
Norio and Iijima, Kentarou and Takemura, Kazuo and Aoshima, Hideyuki
and Someya, Toshiyuki},
title = {Diagnostic classification of schizophrenia by neural network analysis
of blood-based gene expression signatures},
journal = {Schizophrenia Research},
year = {2010},
volume = {119},
pages = {210--218},
number = {1-3},
month = jun,
abstract = {Gene expression profiling with microarray technology suggests that
peripheral blood cells might be a surrogate for postmortem brain
tissue in studies of schizophrenia. The development of an accessible
peripheral biomarker would substantially help in the diagnosis of
this disease. We used a bioinformatics approach to examine whether
the gene expression signature in whole blood contains enough information
to make a specific diagnosis of schizophrenia. Unpaired t-tests of
gene expression datasets from 52 antipsychotics-free schizophrenia
patients and 49 normal controls identified 792 differentially expressed
probes. Functional profiling with DAVID revealed that eleven of these
genes were previously reported to be associated with schizophrenia,
and 73 of them were expressed in the brain tissue. We analyzed the
datasets with one of the supervised classifiers, artificial neural
networks (ANNs). The samples were subdivided into training and testing
sets. Quality filtering and stepwise forward selection identified
14 probes as predictors of the diagnosis. ANNs were then trained
with the selected probes as the input and the training set for known
diagnosis as the output. The constructed model achieved 91.2% diagnostic
accuracy in the training set and 87.9% accuracy in the hold-out testing
set. On the other hand, hierarchical clustering, a standard but unsupervised
classifier, failed to separate patients and controls. These results
suggest analysis of a blood-based gene expression signature with
the supervised classifier, ANNs, might be a diagnostic tool for schizophrenia.},
issn = {0920-9964},
keywords = {Schizophrenia, cDNA microarray, Artificial neural network, Bioinformatics,
Biomarker},
url = {http://www.sciencedirect.com/science/article/B6TC2-4Y64DHW-2/2/6d404dfc64c4ee15c52057ef5384b135}
}
@ARTICLE{Takahashi2009a,
author = {Takahashi, Masaki and Negishi, Takayuki and Imamura, Makoto and Sawano,
Erika and Kuroda, Yoichiro and Yoshikawa, Yasuhiro and Tashiro, Tomoko},
title = {Alterations in gene expression of glutamate receptors and exocytosis-related
factors by a hydroxylated-polychlorinated biphenyl in the developing
rat brain},
journal = {Toxicology},
year = {2009},
volume = {257},
pages = {17--24},
number = {1-2},
month = mar,
abstract = {Polychlorinated biphenyls (PCBs), major environmental hormonally active
agents, are metabolized into hydroxylated PCBs in the liver to facilitate
excretion. Some of hydroxylated PCBs also have potencies disturbing
endogenous hormonal activities at least in vitro. Hormonal activities
of hydroxylated PCBs raise a possibility of their interfering with
normal brain development which is strictly regulated by endogenous
hormones. We investigated whether and how prenatal exposure to a
congener of hydroxylated PCBs (4-OH-2',3,3',4',5'-penta CB; 4-OH-PCB106)
having activities to disrupt thyroid hormone-dependent signals in
vitro could perturb normal gene expression in the developing brain
in vivo. Pregnant rats were exposed to 4-OH-PCB106 subcutaneously
at the dose of 1.0 mg/(kg day) from day 7 of gestation to postnatal
day 1. Then three brain regions (cerebral cortex, hippocampus and
striatum) were obtained from offspring on postnatal day 1 and subjected
to further gene expression analyses. Comprehensive analyses of mRNA
expression by oligo DNA microarrays and subsequent validations by
quantitative RT-PCR revealed that prenatal exposure to 4-OH-PCB106
affected mRNA expression of glutamate receptors as well as that of
thyroid hormone-responsive genes in region-specific manners. Concomitantly
4-OH-PCB106 exposure increased mRNA expression of genes related to
exocytosis in the three brain regions. These results raise the possibility
that prenatal exposure to some hydroxylated PCBs with thyroid hormone-disrupting
potencies leads to abnormal brain development via perturbations on
the expression of genes involved in glutamatergic neurotransmission.},
issn = {0300-483X},
keywords = {Hydroxylated-polychlorinated biphenyl, Gene expression profiling,
Thyroid hormone, Glutamate, Prenatal exposure, Brain development},
url = {http://www.sciencedirect.com/science/article/B6TCN-4V3SY86-4/2/5f9730cb27a5437cb61da4533a1b18dc}
}
@ARTICLE{Takahashi2008,
author = {Takahashi, Masaki and Negishi, Takayuki and Tashiro, Tomoko},
title = {Identification of genes mediating thyroid hormone action in the developing
mouse cerebellum},
journal = {Journal of Neurochemistry},
year = {2008},
volume = {104},
pages = {640--652},
number = {3},
abstract = {Abstract Despite the indispensable role thyroid hormone (TH) plays
in brain development, only a small number of genes have been identified
to be directly regulated by TH and its precise mechanism of action
remains largely unknown, partly because most of the previous studies
have been carried out at postnatal day 15 or later. In the present
study, we screened for TH-responsive genes in the developing mouse
cerebellum at postnatal day 4 when morphological alterations because
of TH status are not apparent. Among the new candidate genes selected
by comparing gene expression profiles of experimentally hypothyroid,
hypothyroid with postnatal thyroxine replacement, and control animals
using oligoDNA microarrays, six genes were confirmed by real-time
PCR to be positively (orc1l, galr3, sort1, nlgn3, cdk5r2, and zfp367)
regulated by TH. Among these, sort1, cdk5r2, and zfp367 were up-regulated
already at 1Â h after a single injection of thyroxine to the hypothyroid
or control animal, suggesting them to be possible primary targets
of the hormone. Cell proliferation and apoptosis examined by BrdU
incorporation and terminal deoxynucleotide transferase-mediated dUTP
nick-end labeling assay revealed that hypothyroidism by itself did
not enhance apoptosis at this stage, but rather increased cell survival,
possibly through regulation of these newly identified genes.},
issn = {1471-4159},
keywords = {apoptosis, cell proliferation, cerebellum, development, DNA microarray,
thyroid hormone},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2007.05049.x}
}
@ARTICLE{Takahashi2004,
author = {Takahashi, Naoko and Kobayashi, Shinya and Jiang, Xu and Kitagori,
Koji and Imai, Kenichi and Hibi, Yurina and Okamoto, Takashi},
title = {Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative
splicing},
journal = {Biochemical and Biophysical Research Communications},
year = {2004},
volume = {315},
pages = {434--438},
number = {2},
month = mar,
abstract = {The p53 binding protein 2 (53BP2) has been initially identified as
an interacting protein to p53 and subsequent studies have shown that
it also interacts with Bcl-2 and NF-[kappa]B p65 subunit. We have
previously found that the TP53BP2 gene encoding 53BP2 protein is
a single copy gene and has been mapped to the long arm of chromosome
1 at q42.1. The subsequent studies revealed that TP53BP2 encodes
two proteins, 53BP2 and ASPP2, of 1005 and 1128 amino acids, respectively.
ASPP2 contains additional 123 amino acids to the N-terminus of 53BP2.
In this study, we have examined the genomic organization of TP53BP2
transcripts and found that it encodes two mRNA species, either with
(53BP2) or without exon 3 (ASPP2), by alternative splicing in various
cell lines and tissues. Thus, we propose to call these proteins as
53BP2S (short) and 53BP2L (long), respectively.},
issn = {0006-291X},
keywords = {TP53BP2, 53BP2, ASPP 2, Apoptosis, p53, Alternative splicing},
url = {http://www.sciencedirect.com/science/article/B6WBK-4BKN0FM-2/2/4374fa9deb47ea3afaba90d57df5ecca}
}
@ARTICLE{Takahashi2008a,
author = {Takahashi, N. and Tsuyama, N. and Sasaki, K. and Kodaira, M. and
Satoh, Y. and Kodama, Y. and Sugita, K. and Katayama, H.},
title = {Segmental Copy-Number Variation Observed in Japanese by Array-CGH},
journal = {Annals of Human Genetics},
year = {2008},
volume = {72},
pages = {193--204},
number = {2},
abstract = {Summary Segmental copy-number variations (CNVs) may contribute to
genetic variation in humans. In this study, we examined 80 unrelated
Japanese individuals using a microarray (2,238 Bac-clones) based
comparative genomic hybridization (array-CGH) assay. We found a total
of 251 CNVs at 30 different regions in the genome; of these, 14 (termed
‘rare’ CNVs) were found individually located within distinct
genomic regions of 14 individuals, while the remaining 16 CNV regions
(termed ‘polymorphic’ CNVs) were observed in two or more individuals.
The rare CNVs were confirmed by quantitative polymerase chain reactions,
and characterized more precisely than in previous reports using array
CGH. Distinctive features of these CNVs were observed: most prominent
was that the majority of the rare CNVs presented on Bac-clones that
did not overlap with regions of segmental duplication. About 90%
of the polymorphic CNVs observed in this population had been previously
identified, with the majority of those polymorphic CNVs located in
regions of segmental duplication. It is likely, therefore, that rare
and polymorphic CNVs arise through different genetic mechanisms.
Since more than half of the rare CNVs are novel, it is also likely
that different human populations bear different CNVs, as is the case
for single-nucleotide-polymorphisms (SNPs) and insertion-deletion
(indel) polymorphisms.},
issn = {1469-1809},
keywords = {Array-CGH, copy-number variation (CNV), Japanese, ethnic difference,
population study},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-1809.2007.00415.x}
}
@ARTICLE{Takahashi2009b,
author = {Takahashi, Shunsuke and Ando, Akira and Takagi, Hiroshi and Shima,
Jun},
title = {Insufficiency of Copper Ion Homeostasis Causes Freeze-Thaw Injury
of Yeast Cells as Revealed by Indirect Gene Expression Analysis},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {6706--6711},
number = {21},
month = nov,
abstract = {Saccharomyces cerevisiae is exposed to freeze-thaw stress in commercial
processes, including frozen dough baking. Cell viability and fermentation
activity after a freeze-thaw cycle were dramatically decreased due
to freeze-thaw injury. Because this type of injury involves complex
phenomena, the injury mechanisms are not fully understood. We examined
freeze-thaw injury by indirect gene expression analysis during postthaw
incubation after freeze-thaw treatment using DNA microarray profiling.
The results showed that genes involved in the homeostasis of metal
ions were frequently contained in genes that were upregulated, depending
on the freezing period. We assessed the phenotype of deletion mutants
of the metal ion homeostasis genes that exhibited freezing period-dependent
upregulation and found that the strains with deletion of the MAC1
and CTR1 genes involved in copper ion homeostasis exhibited freeze-thaw
sensitivity, suggesting that copper ion homeostasis is required for
freeze-thaw tolerance. We found that supplementation with copper
ions during postthaw incubation increased intracellular superoxide
dismutase activity and intracellular levels of reactive oxygen species
were decreased. Moreover, cell viability was increased by supplementation
with copper ions. These results suggest that insufficiency of copper
ion homeostasis may be one of the causes of freeze-thaw injury.},
url = {http://aem.asm.org/cgi/content/abstract/75/21/6706}
}
@ARTICLE{Takahashi2008b,
author = {Takahashi, Shin and Moriya, Takuya and Ishida, Takanori and Shibata,
Hiroyuki and Sasano, Hironobu and Ohuchi, Noriaki and Ishioka, Chikashi},
title = {Prediction of breast cancer prognosis by gene expression profile
of TP53 status},
journal = {Cancer Science},
year = {2008},
volume = {99},
pages = {324--332},
number = {2},
abstract = {TP53 mutations are a poor prognostic factor in breast cancers. The
present study sets out to identify the gene set that determines the
expression signature of the TP53 status (TP53 signature) and to correlate
it with clinical outcome. Using comprehensive expression analysis
and DNA sequencing of the TP53 gene in 38 Japanese breast cancer
patients, a gene set from differentially expressed genes was isolated,
depending on the TP53 status. As independent external datasets, two
published datasets were introduced for validation of TP53 status
predictions (251 Swedish samples) and survival analysis (both the
Swedish and 295 Dutch samples). Thirty-three gene sets were identified
from microarray analysis. Predictive accuracy of the TP53 status
by gene expression profiling was 83.3% in the test set (n = 12).
TP53 signature has the ability to predict recurrence-free survival
(RFS) of 29 stage I and stage II Japanese breast cancers (log rank,
PÂ =Â 0.032), and RFS, overall survival of two independently published
datasets (log rank, both PÂ <Â 0.0001). Multivariate analysis has
shown that the TP53 signature an independent and significant prognostic
factor with a hazard ratio (HR) for recurrence and survival in two
external datasets (PÂ <Â 0.0001). The TP53 signature is also a strong
prognostic factor in the subgroups: estrogen-receptor positive, lymph
node positive and negative, intermediate/high risk in St. Gallen
criteria, and high risk in National Cancer Institute (NCI) criteria
(log rank, PÂ <Â 0.0001). TP53 signature is a reliable and independent
predictor of the outcome of disease in operated breast cancer. (Cancer
Sci 2008; 99: 324–332)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2007.00691.x}
}
@ARTICLE{Takahashi2005,
author = {Takahashi, T. and Nakayama, T. and Tamura, M. and Ogawa, K. and Tsuda,
H. and Morita, A. and Hara, M. and Togo, M. and Shiota, H. and Suzuki,
Y. and Minami, M. and Ishikawa, H. and Miki, K. and Shikata, E. and
Takahashi, S. and Kuragano, T. and Matsumoto, K. and Sawada, S. and
Mizutani, T.},
title = {Nested polymerase chain reaction for assessing the clinical course
of tuberculous meningitis},
journal = {Neurology},
year = {2005},
volume = {64},
pages = {1789--1793},
number = {10},
month = may,
abstract = {The authors examined the usefulness of nested PCR (N-PCR) to detect
Mycobacterium tuberculosis (MTB) DNA in CSF for assessing the clinical
course of tuberculous meningitis (TBM). N-PCR successfully detected
MTB DNA in all nine CSF samples from patients with suspected TBM.
During anti-tuberculosis treatments, N-PCR results converted from
positive to negative, correlating with the improvement of the patient's
clinical condition.},
url = {http://www.neurology.org/cgi/content/abstract/64/10/1789}
}
@ARTICLE{Takahashi2008c,
author = {Takahashi, Teruyuki and Tamura, Masato and Asami, Yukihiro and Kitamura,
Eiko and Saito, Kosuke and Suzuki, Tsukasa and Takahashi, Sachiko
Nonaka and Matsumoto, Koichi and Sawada, Shigemasa and Yokoyama,
Eise and Takasu, Toshiaki},
title = {Novel Wide-Range Quantitative Nested Real-Time PCR Assay for Mycobacterium
tuberculosis DNA: Clinical Application for Diagnosis of Tuberculous
Meningitis},
journal = {J. Clin. Microbiol.},
year = {2008},
volume = {46},
pages = {1698--1707},
number = {5},
month = may,
abstract = {Although the "gold standard" for diagnosis of tuberculous meningitis
(TBM) is bacterial isolation of Mycobacterium tuberculosis, there
are still several complex issues. Recently, we developed an internally
controlled novel wide-range quantitative nested real-time PCR (WR-QNRT-PCR)
assay for M. tuberculosis DNA in order to rapidly diagnose TBM. For
use as an internal control calibrator to measure the copy number
of M. tuberculosis DNA, an original new-mutation plasmid (NM-plasmid)
was developed. Due to the development of the NM-plasmid, the WR-QNRT-PCR
assay demonstrated statistically significant accuracy over a wide
detection range (1 to 105 copies). In clinical applications, the
WR-QNRT-PCR assay revealed sufficiently high sensitivity (95.8%)
and specificity (100%) for 24 clinically suspected TBM patients.
In conditional logistic regression analysis, a copy number of M.
tuberculosis DNA (per 1 ml of cerebrospinal fluid) of >8,000 was
an independent risk factor for poor prognosis for TBM (i.e., death)
(odds ratio, 16.142; 95% confidence interval, 1.191 to 218.79; P
value, 0.0365). In addition, the copy numbers demonstrated by analysis
of variance statistically significant alterations (P < 0.01) during
the clinical treatment course for 10 suspected TBM patients. In simple
regression analysis, the significant correlation (R2 = 0.597; P <
0.0001) was demonstrated between copy number and clinical stage of
TBM. We consider the WR-QNRT-PCR assay to be a useful and advanced
assay technique for assessing the clinical treatment course of TBM.},
url = {http://jcm.asm.org/cgi/content/abstract/46/5/1698}
}
@ARTICLE{Takahashi2007,
author = {Takahashi, Teruyuki and Tamura, Masato and Takahashi, Sachiko Nonaka
and Matsumoto, Koichi and Sawada, Shigemasa and Yokoyama, Eise and
Nakayama, Tomohiro and Mizutani, Tomohiko and Takasu, Toshiaki and
Nagase, Hiroki},
title = {Quantitative nested real-time PCR assay for assessing the clinical
course of tuberculous meningitis},
journal = {Journal of the Neurological Sciences},
year = {2007},
volume = {255},
pages = {69--76},
number = {1-2},
month = apr,
abstract = {Although the "gold standard" for diagnosis of tuberculous meningitis
(TBM) is bacterial isolation of Mycobacterium tuberculosis (M. Tb),
there are still several complex issues. Recently, in the diagnosis
of TBM, the detection of M. Tb DNA in cerebrospinal fluid (CSF) samples
using PCR has been widely performed as more rapid, sensitive, and
specific diagnostic method. Based on Taq Man® PCR, the authors developed
a novel technique of internally controlled quantitative nested real-time
(QNRT) PCR assay that provided a prominent improvement in detection
sensitivity and quantification. Total 43 CSF samples from 8 serial
patients with suspected TBM were analyzed. The CSF samples were collected
before and during standard anti-tuberculosis treatments (ATT). The
QNRT-PCR assay revealed positive results for 24 out of 43 serial
CSF samples (55.8%) collected during the treatment course of ATT.
Moreover, the bacterial cell (BC) numbers of M. Tb analyzed by the
QNRT-PCR assay decreased gradually, correlating with the improvements
of the patient's clinical conditions. Since the QNRT-PCR assay provides
the ability to calculate a numerical value for the initial BC numbers
of M. Tb in CSF samples, this method is an extremely useful and advanced
technique for use in assessing the clinical course of TBM.},
issn = {0022-510X},
keywords = {Quantitative nested real-time (QNRT) PCR, TaqMan® PCR, Nested PCR,
Mycobacterium tuberculosis, Tuberculous meningitis, Cerebrospinal
fluid},
url = {http://www.sciencedirect.com/science/article/B6T06-4N74JDS-4/2/6ed8f6c22bfd99fee5c0990b1c7844ca}
}
@ARTICLE{Takai2005,
author = {Takai, Noriyuki and Kawamata, Norihiko and Walsh, Christine S. and
Gery, Sigal and Desmond, Julian C. and Whittaker, Sadie and Said,
Jonathan W. and Popoviciu, Laura M. and Jones, Peter A. and Miyakawa,
Isao and Koeffler, H. Phillip},
title = {Discovery of Epigenetically Masked Tumor Suppressor Genes in Endometrial
Cancer},
journal = {Mol. Cancer Res.},
year = {2005},
volume = {3},
pages = {261--269},
number = {5},
month = may,
abstract = {Realization that many tumor suppressor genes are silenced by epigenetic
mechanisms has stimulated the discovery of novel tumor suppressor
genes. We used a variety of research tools to search for genes that
are epigenetically silenced in human endometrial cancers. Changes
in global gene expression of the endometrial cancer cell line Ishikawa
was analyzed after treatment with the demethylating agent 5-aza-2'-deoxycytidine
combined with the histone deacetylase inhibitor suberoylanilide bishydroxamide.
By screening over 22,000 genes, candidate tumor suppressor genes
were identified. Additional microarray analysis and real-time reverse
transcription-PCR of normal and cancerous endometrial samples and
search for CpG islands further refined the list. Tazarotene-induced
gene-1 (Tig1) and CCAAT/enhancer binding protein-{alpha} (C/ebp{alpha})
were chosen for further study. Expression of both genes was low in
endometrial cancer cell lines and clinical samples but high in normal
endometrial tissues. Bisulfite sequencing, restriction analysis,
and/or methylation-specific PCR revealed aberrant methylation of
the CpG island in the Tig1 gene of all 6 endometrial cancer cell
lines examined and 4 of 18 clinical endometrial cancers, whereas
the C/ebp{alpha} promoter remained unmethylated in endometrial cancers.
Chromatin immunoprecipitation showed increased acetylated histone
H3 bound to both Tig1 and C/ebp{alpha} genes after treatment with
5-aza-2'-deoxycytidine and/or suberoylanilide bishydroxamide. Forced
expression of either TIG1 or C/EBP{alpha} led to significant growth
reduction of Ishikawa cells. Our data suggest that C/ebp{alpha} and
Tig1 function as tumor suppressor proteins in endometrial cancers
and that their reexpression may be a therapeutic target.},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/3/5/261}
}
@ARTICLE{Takaku2005,
author = {Takaku, Tomoiku and Ohyashiki, Junko H. and Zhang, Yu and Ohyashiki,
Kazuma},
title = {Estimating immunoregulatory gene networks in human herpesvirus type
6-infected T cells},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {336},
pages = {469--477},
number = {2},
month = oct,
abstract = {The immune response to viral infection involves complex network of
dynamic gene and protein interactions. We present here the dynamic
gene network of the host immune response during human herpesvirus
type 6 (HHV-6) infection in an adult T-cell leukemia cell line. Using
a pathway-focused oligonucleotide DNA microarray, we found a possible
association between chemokine genes regulating Th1/Th2 balance and
genes regulating T-cell proliferation during HHV-6B infection. Gene
network analysis using an integrated comprehensive workbench, VoyaGene,
revealed that a gene encoding a TEC-family kinase, ITK, might be
a putative modulator in the host immune response against HHV-6B infection.
We conclude that Th2-dominated inflammatory reaction in host cells
may play an important role in HHV-6B-infected T cells, thereby suggesting
the possibility that ITK might be a therapeutic target in diseases
related to dysregulation of Th1/Th2 balance. This study describes
a novel approach to find genes related with the complex host-virus
interaction using microarray data employing the Bayesian statistical
framework.},
issn = {0006-291X},
keywords = {DNA microarray, Human herpesvirus type 6, Bayesian network model,
Th2 response},
url = {http://www.sciencedirect.com/science/article/B6WBK-4GY8433-6/2/f10ee37c539fc23082a8a3cb195e65a7}
}
@ARTICLE{Takamiya2007,
author = {Takamiya, Minako and Lambard, Sophie and Huhtaniemi, Ilpo T.},
title = {Effect of bisphenol A on human chorionic gonadotrophin-stimulated
gene expression of cultured mouse Leydig tumour cells},
journal = {Reproductive Toxicology},
year = {2007},
volume = {24},
pages = {265--275},
number = {2},
month = aug,
abstract = {Endocrine disrupting chemicals (EDCs) have been reported to affect
the reproductive system of various animal species. However, their
specific effects and modes of action on gonadal function remain largely
unclear. We studied the effects of a model EDC, bisphenol A (BPA),
on human chorionic gonadotrophin (hCG)-stimulated global gene expression
of cultured mouse Leydig tumour cells (mLTC-1). The time and dose
of BPA exposure were set after semiquantitative (sq) RT-PCR analysis
of response of candidate genes (StAR, Cyp17a1 and AR) to 3 h at 10 [mu]g/l
hCG ± 10-5 M BPA. Affymetrix microarray analysis demonstrated >=1.5-fold
up-regulation of 8- and <=1.5-fold down-regulated of 16 genes by
BPA. Several of these genes were related to steroid/cholesterol metabolism/transport
and cell cycle regulation. sqRT-PCR demonstrated induction of StAR
expression by hCG stimulation and no effect of BPA. In conclusion,
our results indicate that BPA has only subtle modulating effects
on gene expression of gonadotrophin-stimulated mLTC-1 cells.},
issn = {0890-6238},
keywords = {Affymetrix, Bisphenol A (BPA), Human chorionic gonadotrophin (hCG),
Endocrine disrupting chemicals (EDCs), Mouse Leydig tumour cells
(mLTC-1), Steroidogenic acute regulatory protein (StAR), Steroidogenesis,
Microarray, Semiquantitative RT-PCR (sqRT-PCR)},
url = {http://www.sciencedirect.com/science/article/B6TC0-4P59X65-1/2/f0760b2d08a74bf95a5915551d20dab9}
}
@ARTICLE{Takano2007,
author = {Takano, Masashi and Lu, Zhenxiao and Goto, Tomoko and Fusi, Luca
and Higham, Jenny and Francis, Julia and Withey, Anna and Hardt,
Jennifer and Cloke, Brianna and Stavropoulou, Alexandra V. and Ishihara,
Osamu and Lam, Eric W.-F. and Unterman, Terry G. and Brosens, Jan
J. and Kim, J. Julie},
title = {Transcriptional Cross Talk between the Forkhead Transcription Factor
Forkhead Box O1A and the Progesterone Receptor Coordinates Cell Cycle
Regulation and Differentiation in Human Endometrial Stromal Cells},
journal = {Mol. Endocrinol.},
year = {2007},
volume = {21},
pages = {2334--2349},
number = {10},
month = oct,
abstract = {Differentiation of human endometrial stromal cells (HESCs) into decidual
cells is associated with induction of the forkhead transcription
factor forkhead box O1A (FOXO1). We performed a genomic screen to
identify decidua-specific genes under FOXO1 control. Primary HESCs
were transfected with small interfering RNA targeting FOXO1 or with
nontargeting control small interfering RNA before treatment with
a cAMP analogue and the progestin, medroxyprogesterone acetate for
72 h. Total RNA was processed for whole genome analysis using high-density
oligonucleotide arrays. We identified 3405 significantly regulated
genes upon decidualization of HESCs, 507 (15.3%) of which were aberrantly
expressed upon FOXO1 knockdown. Among the most up-regulated FOXO1-dependent
transcriptional targets were WNT signaling-related genes (WNT4, WNT16
), the insulin receptor (INSR), differentiation markers (PRL, IGFBP1,
and LEFTY2), and the cyclin-dependent kinase inhibitor p57Kip2 (CDKN1C).
Analysis of FOXO1-dependent down-regulated genes uncovered several
factors involved in cell cycle regulation, including CCNB1, CCNB2,
MCM5, CDC2 and NEK2. Cell viability assay and cell cycle analysis
demonstrated that FOXO1 silencing promotes proliferation of differentiating
HESCs. Using a glutathione-S-transferase pull-down assay, we confirmed
that FOXO1 interacts with progesterone receptor, irrespectively of
the presence of ligand. In agreement, knockdown of PR disrupted the
regulation of FOXO1 target genes involved in differentiation (IGFBP1,
PRL, and WNT4) and cell cycle regulation (CDKN1, CCNB2 and CDC2)
in HESCs treated with either cAMP plus medroxyprogesterone acetate
or with cAMP alone. Together, the data demonstrate that FOXO1 engages
in transcriptional cross talk with progesterone receptor to coordinate
cell cycle regulation and differentiation of HESCs.},
url = {http://mend.endojournals.org/cgi/content/abstract/21/10/2334}
}
@ARTICLE{Takatsu2004,
author = {Takatsu, Kyoko and Yokomaku, Toyokazu and Kurata, Shinya and Kanagawa,
Takahiro},
title = {A FRET-based analysis of SNPs without fluorescent probes},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {e156--},
number = {19},
month = nov,
abstract = {Fluorescence resonance energy transfer (FRET) is a simple procedure
for detecting specific DNA sequences, and is therefore used in many
fields. However, the cost is relatively high, because FRET-based
methods usually require fluorescent probes. We have designed a cost-effective
way of using FRET, and developed a novel approach for the genotyping
of single nucleotide polymorphisms (SNPs) and allele frequency estimation.
The key feature of this method is that it uses a DNA-binding fluorogenic
molecule, SYBR Green I, as an energy donor for FRET. In this method,
single base extension is performed with dideoxynucleotides labeled
with an orange dye and a red dye in the presence of SYBR Green I.
The dyes incorporated into the extended products accept energy from
SYBR Green I and emit fluorescence. We have validated the method
with ten SNPs, which were successfully discriminated by end-point
measurements of orange and red fluorescence intensity in a microplate
fluorescence reader. Using a mixture of homozygous samples, we also
confirmed the potential of this method for estimation of allele frequency.
Application of this strategy to large-scale studies will reduce the
time and cost of genotyping a vast number of SNPs.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/19/e156}
}
@ARTICLE{Takayama2009,
author = {Takayama, Tomohiro and Takada, Naoki and Suzuki, Rie and Nagaoka,
Shunsuke and Watanabe, Yoshihisa and Kumagai, Reiko and Aoki, Yasuhiro
and Butler, John M.},
title = {Determination of deleted regions from Yp11.2 of an amelogenin negative
male},
journal = {Legal Medicine},
year = {2009},
volume = {11},
pages = {S578--S580},
number = {Supplement 1},
month = apr,
abstract = {The use of short tandem repeat (STR) multiplexes with the incorporated
gender marker amelogenin is now common practice in forensic laboratories.
The amelogenin locus is encoded by two single copy genes located
on Xp22.1-Xp22.3 (AMELX) and Yp11.2 (AMELY). There are differences
in size and sequence between AMELX and AMELY that can be used for
sex-typing tests. A sized-based difference for AMELX and AMELY is
an integral part of most PCR multiplex kits that are used for DNA
profiling. However, we experienced a case of a normal male being
typed as female (dropout of the amelogenin Y allele) with AmpFlSTR
Profiler kit, AmpFlSTR Identifiler kit and PowerPlex 16 System. Further
testing with Y-STR loci using the AmpFlSTR Yfiler kit revealed an
additional null at DYS458 locus in this amelogenin negative male.
We examined the deleted regions using a total of 60 loci from Y-STRs,
STSs (sequence tagged sites) and newly designed primer sets. Three
deleted regions in Yp11.2 were seen in this sample. The sizes of
these deletions were approximately 2.51 Mb, 25 kb and 834b, respectively.
The deletions did not belong to the five reported patterns in a collection
of 45 deletion males from 12 populations described by Jobling et
al.},
booktitle = {Selected papers from the 7th International Symposium ADVANCES IN
LEGAL MEDICINE (ISALM), 7th International Symposium ADVANCES IN LEGAL
MEDICINE (ISALM)},
issn = {1344-6223},
keywords = {Amelogenin, Deletion, Yp11.2, DYS458, AMELY negative},
url = {http://www.sciencedirect.com/science/article/B6W7W-4VS9M2K-F/2/d9cad5dfd08addbdba1d7f202dacce84}
}
@ARTICLE{Takehisa2012,
author = {Takehisa, Hinako and Sato, Yutaka and Igarashi, Motoko and Abiko,
Tomomi and Antonio, Baltazar A. and Kamatsuki, Kaori and Minami,
Hiroshi and Namiki, Nobukazu and Inukai, Yoshiaki and Nakazono, Mikio
and Nagamura, Yoshiaki},
title = {Genome-wide transcriptome dissection of the rice root system: implications
for developmental and physiological functions},
journal = {The Plant Journal},
year = {2012},
volume = {69},
pages = {126--140},
number = {1},
abstract = {The root system is a crucial determinant of plant growth potential
because of its important functions, e.g. uptake of water and nutrients,
structural support and interaction with symbiotic organisms. Elucidating
the molecular mechanism of root development and functions is therefore
necessary for improving plant productivity, particularly for crop
plants, including rice (Oryza sativa). As an initial step towards
developing a comprehensive understanding of the root system, we performed
a large-scale transcriptome analysis of the rice root via a combined
laser microdissection and microarray approach. The crown root was
divided into eight developmental stages along the longitudinal axis
and three radial tissue types at two different developmental stages,
namely: epidermis, exodermis and sclerenchyma; cortex; and endodermis,
pericycle and stele. We analyzed a total of 38 microarray data and
identified 22Â 297 genes corresponding to 17Â 010 loci that showed
sufficient signal intensity as well as developmental- and tissue
type-specific transcriptome signatures. Moreover, we clarified gene
networks associated with root cap function and lateral root formation,
and further revealed antagonistic and synergistic interactions of
phytohormones such as auxin, cytokinin, brassinosteroids and ethylene,
based on the expression pattern of genes related to phytohormone
biosynthesis and signaling. Expression profiling of transporter genes
defined not only major sites for uptake and transport of water and
nutrients, but also distinct signatures of the radial transport system
from the rhizosphere to the xylem vessel for each nutrient. All data
can be accessed from our gene expression profile database, RiceXPro
(http://ricexpro.dna.affrc.go.jp), thereby providing useful information
for understanding the molecular mechanisms involved in root system
development of crop plants.},
doi = {10.1111/j.1365-313X.2011.04777.x},
issn = {1365-313X},
keywords = {transcriptome, rice, root, laser microdissection, microarray, database},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2011.04777.x}
}
@BOOK{Takematsu2007,
title = {DNA Microarrays in Glycobiology},
publisher = {Elsevier},
year = {2007},
editor = {Kamerling, Johannis P.},
author = {Takematsu, H. and Kozutsumi, Y.},
pages = {427--448},
address = {Oxford},
booktitle = {Comprehensive Glycoscience},
issn = {978-0-44-451967-2},
url = {http://www.sciencedirect.com/science/article/B8SB9-4PGB1SG-3Y/2/95f697d74558c991e6b0f07e5d93f9d1}
}
@ARTICLE{Takemura2005,
author = {Takemura, Fumiyo and Inaba, Niro and Miyoshi, Eiji and Furuya, Takako
and Terasaki, Hiroshi and Ando, Satoshi and Kinoshita, Noriaki and
Ogawa, Yoshiyasu and Taniguchi, Naoyuki and Ito, Satoru},
title = {Optimization of liver biopsy RNA sampling and use of reference RNA
for cDNA microarray analysis},
journal = {Analytical Biochemistry},
year = {2005},
volume = {337},
pages = {224--234},
number = {2},
month = feb,
abstract = {In this study, we used the rat liver as a model system to optimize
the conditions for extracting RNA from liver biopsies for use in
cDNA microarrays. We found that a 5-mm biopsy with a 16-gauge needle
and storage in RNAlater at 4 °C were optimal conditions for RNA extraction.
The most important factor for the quantity and quality of RNA extraction
was the sample diameter. Using the optimized sampling conditions
and a cDNA microarray, we compared the expression of genes in the
normal and the fibrotic tissues of the LEC rat liver, a model of
liver tumorigenesis, with SD rat liver RNA as a reference. We found
29 genes that were up-regulated and 33 genes that were down-regulated
in the fibrotic part of the liver. Furthermore, with the help of
the reference RNA, we were able to classify the expression profiles
into five groups without complex mathematical analyses; without the
reference RNA, the genes could be classified into only two groups.
Finally, we found that osteopontin was expressed at a very high level
in the fibrotic portion of the LEC rat liver. This cDNA microarray
result was validated by immunohistochemistry, which showed an elevated
expression of osteopontin in the region of cholangiocarcinoma and
a lack of expression in normal tissues. With optimized conditions,
we should be able to apply the microarray system for routine practice.},
issn = {0003-2697},
keywords = {RNA handling conditions, cDNA microarray, Reference RNA, LEC rat model,
Tumorigenesis, Osteopontin},
url = {http://www.sciencedirect.com/science/article/B6W9V-4F00PM5-1/2/4e344d73fb0af03b7486e93a6f8ceddd}
}
@ARTICLE{Takeuchi2008,
author = {Takeuchi, Kengo and Choi, Young Lim and Soda, Manabu and Inamura,
Kentaro and Togashi, Yuki and Hatano, Satoko and Enomoto, Munehiro
and Takada, Shuji and Yamashita, Yoshihiro and Satoh, Yukitoshi and
Okumura, Sakae and Nakagawa, Ken and Ishikawa, Yuichi and Mano, Hiroyuki},
title = {Multiplex Reverse Transcription-PCR Screening for EML4-ALK Fusion
Transcripts},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6618--6624},
number = {20},
month = oct,
abstract = {Purpose: EML4-ALK is a fusion-type protein tyrosine kinase that is
generated by inv(2)(p21p23) in the genome of non-small cell lung
cancer (NSCLC). To allow sensitive detection of EML4-ALK fusion transcripts,
we have now developed a multiplex reverse transcription-PCR (RT-PCR)
system that captures all in-frame fusions between the two genes.
Experimental Design: Primers were designed to detect all possible
in-frame fusions of EML4 to exon 20 of ALK, and a single-tube multiplex
RT-PCR assay was done with total RNA from 656 solid tumors of the
lung (n = 364) and 10 other organs. Results: From consecutive lung
adenocarcinoma cases (n = 253), we identified 11 specimens (4.35%)
positive for fusion transcripts, 9 of which were positive for the
previously identified variants 1, 2, and 3. The remaining two specimens
harbored novel transcript isoforms in which exon 14 (variant 4) or
exon 2 (variant 5) of EML4 was connected to exon 20 of ALK. No fusion
transcripts were detected for other types of lung cancer (n = 111)
or for tumors from 10 other organs (n = 292). Genomic rearrangements
responsible for the fusion events in NSCLC cells were confirmed by
genomic PCR analysis and fluorescence in situ hybridization. The
novel isoforms of EML4-ALK manifested marked oncogenic activity,
and they yielded a pattern of cytoplasmic staining with fine granular
foci in immunohistochemical analysis of NSCLC specimens. Conclusions:
These data reinforce the importance of accurate diagnosis of EML4-ALK-positive
tumors for the optimization of treatment strategies.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/20/6618}
}
@ARTICLE{Takeyama2006,
author = {Takeyama, Kazuhide and Yoshikawa, Masanobu and Oka, Tetsuo and Kawaguchi,
Mitsuru and Suzuki, Toshiyasu and Hashimoto, Atsushi},
title = {Ketamine enhances the expression of serine racemase and d-amino acid
oxidase mRNAs in rat brain},
journal = {European Journal of Pharmacology},
year = {2006},
volume = {540},
pages = {82--86},
number = {1-3},
month = jul,
abstract = {We have evaluated the effects of the acute administration of noncompetitive
N-methyl-d-aspartate receptor antagonist, ketamine, on the expression
of serine racemase and d-amino acid oxidase mRNAs in several brain
areas of rats. The ketamine administration produced a dose-dependent
and transient elevation in the levels of serine racemase and d-amino
acid oxidase mRNAs in all the brain areas. These findings suggest
that there is a relationship between the gene expression of the d-serine-related
enzymes and the blockade of the N-methyl-d-aspartate receptors.},
issn = {0014-2999},
keywords = {d-Amino acid oxidase, Anesthetics, Ketamine, NMDA receptor, Schizophrenia,
Serine racemase},
url = {http://www.sciencedirect.com/science/article/B6T1J-4JTXCTD-1/2/68dec1c7f8385dcdf39ba58baa32ae4a}
}
@ARTICLE{Takikawa2009,
author = {Takikawa, Masako and Akiyama, Yasuto and Ashizawa, Tadashi and Yamamoto,
Akifumi and Yamazaki, Naoya and Kiyohara, Yoshio and Oku, Naoto and
Yamaguchi, Ken},
title = {Identification of melanoma-specific serological markers using proteomic
analyses},
journal = {Prot. Clin. Appl.},
year = {2009},
volume = {3},
pages = {552--562},
number = {5},
abstract = {Abstract The discovery of novel melanoma markers for not only early
detection but also monitoring disease status is promising to improve
the clinical outcome of patients. In the present study, we performed
proteomic comparative analysis of plasma proteins between healthy
volunteers and melanoma patients using NanoLC and MALDI-TOF-MS. As
a result, we were successful in identifying nine proteins that were
specifically expressed in melanoma plasma compared with healthy plasma,
most of which had not previously been identified as plasma markers
of melanoma. The mRNA expression levels of four proteins [pro-platelet
basic protein precursor (PPBP), serum amyloid A2 (SAA2), complement
factor H-related protein 1 precursor (FHR1), inter-alpha-trypsin
inhibitor heavy chain H4 precursor (IAIH4)] were prominently up-regulated
in several melanoma cell lines compared with melanocytes. Moreover,
two proteins (PPBP, SAA) were shown to be expressed in tumor specimens
from melanoma patients. In the survival time analysis regarding melanoma
patients, the semi-quantified plasma PPBP levels were statistically
negatively correlated with the survival time. Most interestingly,
the significant survival benefit was seen in low PBPP level group
(< index 20) versus high level (≥ index 20) group. The results
suggest that PPBP might be a novel promising serological marker and
a prognostic factor specific to melanomas.},
issn = {1862-8354},
keywords = {Chemokine, Metastatic melanoma, Nano-LC-MS/MS, Plasma marker, Proteomics},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/prca.200800165}
}
@ARTICLE{Takle2006,
author = {Takle, Harald and McLeod, Anette and Andersen, Oivind},
title = {Cloning and characterization of the executioner caspases 3, 6, 7
and Hsp70 in hyperthermic Atlantic salmon (Salmo salar) embryos},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2006},
volume = {144},
pages = {188--198},
number = {2},
month = jun,
abstract = {Hyperthermia during embryogenesis has been reported to induce deformities
in Atlantic salmon (Salmo salar). To examine the involvement of executioner
caspases in hyperthermia-induced cell-death in a poikilotherm vertebrate
species, five genes encoding caspase-3,-6, and -7 were cloned from
Atlantic salmon, and the expression was studied in thermal stressed
salmon embryos. The salmon genome contained two genetically distinct
variants of both salmon caspase-3 and caspase-6 that is likely the
result of two independent chromosome or genome duplications. Whereas
only partial caspase-3A encoding sequences were isolated, the full-length
caspase-3B cDNA encodes the inactive proenzyme of 279 amino acids
(aa) consisting of an N-terminal prodomain and the large and the
small subunit. The salmon caspase-6A and caspase-6B proenzymes include
an additional linker region between the two subunits. The deduced
salmon caspase-7 consists of only 245 aa and lacks the prodomain
and part of the large subunit similar to the predicted caspase-7
of the puffer fish Tetraodon sp.. Increased apoptotic activity as
evidenced by cleavage of nuclear DNA was demonstrated in salmon embryos
incubated at 18-20 °C for 84 h after acclimatization at 8 °C. Hyperthermia-induced
activation of the executioner caspases was indicated by the increased
mRNA levels of caspase-3B, caspase-6A/B and caspase-7 after 54 h
heat exposure as quantified by real-time RT-PCR. The 2-2.5 fold increase
in the mRNA expression of the heat shock protein Hsp70 gene coincided
with the peak mRNA values of the executioner caspases. Whole-mount
in situ hybridization of the salmon embryo identified caspase-7 mRNA
in the lens exclusively, while caspase-3B and caspase-6A/B were expressed
in multiple tissues of exposed and control embryos. Interestingly,
cardiac expression of caspase-6A/B was only identified in heat stressed
embryos. Altogether, these results shed light on evolutionary aspects
of the executioner caspases in vertebrates and their expression in
salmon embryos exposed to hyperthermia. In particular, the heat sensitive
caspase-6 expression in the embryonic heart is of interest since
cardiac malformations are an emergent problem in salmon aquaculture.},
issn = {1096-4959},
keywords = {Apoptosis, Caspase-3, Caspase-6, Caspase-7, Deformities, Development,
Heat exposure, Hsp70},
url = {http://www.sciencedirect.com/science/article/B6T2R-4JDN6K7-2/2/e752ab134f7cafb83528422aa6688515}
}
@ARTICLE{Talantov2006,
author = {Talantov, Dimitri and Baden, Jonathan and Jatkoe, Tim and Hahn, Kristina
and Yu, Jack and Rajpurohit, Yashoda and Jiang, Yiqiu and Choi, Chang
and Ross, Jeffrey S. and Atkins, David and Wang, Yixin and Mazumder,
Abhijit},
title = {A Quantitative Reverse Transcriptase-Polymerase Chain Reaction Assay
to Identify Metastatic Carcinoma Tissue of Origin},
journal = {J. Mol. Diagn.},
year = {2006},
volume = {8},
pages = {320--329},
number = {3},
month = jul,
abstract = {Identifying the primary site in patients with metastatic carcinoma
of unknown primary origin can enable more specific therapeutic regimens
and may prolong survival. Twenty-three putative tissue-specific markers
for lung, colon, pancreatic, breast, prostate, and ovarian carcinomas
were nominated by querying a gene expression profile database and
by performing a literature search. Ten of these marker candidates
were then selected based on validation by reverse transcriptase-polymerase
chain reaction (RT-PCR) on 205 formalin-fixed, paraffin-embedded
metastatic carcinoma specimens originating from these six and from
other cancer types. Next, we optimized the RNA isolation and quantitative
RT-PCR methods for these 10 markers and applied the quantitative
RT-PCR assay to a set of 260 metastatic tumors. We then built a gene-based
algorithm that predicted the tissue of origin of metastatic carcinomas
with an overall leave-one-out cross-validation accuracy of 78%. Lastly,
our assay demonstrated an accuracy of 76% when tested on an independent
set of 48 metastatic samples, 37 of which were either a known primary
or initially presented as carcinoma of unknown primary but were subsequently
resolved.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/8/3/320}
}
@ARTICLE{Talantov2005,
author = {Talantov, Dmitri and Mazumder, Abhijit and Yu, Jack X. and Briggs,
Thomas and Jiang, Yuqiu and Backus, John and Atkins, David and Wang,
Yixin},
title = {Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic
Lesions},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {7234--7242},
number = {20},
month = oct,
abstract = {Purpose: Cutaneous melanoma is a common, aggressive cancer with increasing
incidence. The identification of melanoma-specific deregulated genes
could provide molecular markers for lymph node staging assays and
further insight into melanoma tumorigenesis. Experimental Design:
Total RNA isolated from 45 primary melanoma, 18 benign skin nevi,
and 7 normal skin tissue specimens were analyzed on an Affymetrix
Hu133A microarray containing 22,000 probe sets. Results: Hierarchical
clustering revealed a distinct separation of the melanoma samples
from the benign and normal specimens. Novel genes associated with
malignant melanoma were identified. Differential gene expression
of two melanoma-specific genes, PLAB and L1CAM, were tested by a
one-step quantitative reverse transcription-PCR assay on primary
malignant melanoma, benign nevi, and normal skin samples, as well
as on malignant melanoma lymph node metastasis and melanoma-free
lymph nodes. The performance of the markers was compared with conventional
melanoma markers such as tyrosinase, gp100, and MART1. Conclusion:
Our study systematically identified novel melanoma-specific genes
and showed the feasibility of using a combination of PLAB and L1CAM
in a reverse transcription-PCR assay to differentiate clinically
relevant samples containing benign or malignant melanocytes.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/20/7234}
}
@ARTICLE{Talbot2009,
author = {Talbot, Anita T. and Pottinger, Tom G. and Smith, Terry J. and Cairns,
Michael T.},
title = {Acute phase gene expression in rainbow trout (Oncorhynchus mykiss)
after exposure to a confinement stressor: A comparison of pooled
and individual data},
journal = {Fish \& Shellfish Immunology},
year = {2009},
volume = {27},
pages = {309--317},
number = {2},
month = aug,
abstract = {This study set out to investigate whether differential expression
of genes for acute phase proteins in rainbow trout (Oncorhynchus
mykiss) could be induced by confinement stress, a non-invasive method
of activating the neuroendocrine stress response. In addition, a
second objective was to assess the variation in gene expression between
individual fish within the population of stressed fish in an attempt
to identify APP genes having uniform and consistent changes in expression
during stress. The liver was chosen for this investigation as it
is the primary site of acute phase protein synthesis. Relative expression
of the eight genes including transferrin, fibrinogen-like protein
2 (flp2), [alpha]-1-anti-proteinase-like protein ([alpha]1-antiprot),
leukocyte cell-derived chemotaxin 2 (LECT2), pentraxin, serum amyloid
A (SAA), haptoglobin (Hp), and differentially regulated trout protein
1 (DRTP1) was analysed by quantitative real-time PCR (qPCR) over
5 experimental time points spanning the course of a week. The results
showed that the expression of three genes, SAA, haptoglobin and DRTP1,
were most altered as a result of exposure to confinement stress.
A correlation was identified between the expression of haptoglobin
and DRTP1. Gene expression analyses in individual fish found that
the transcript levels of haptoglobin and DRTP1 genes varied much
less between individuals than was the case for SAA. The increase
of haptoglobin and DRTP1 gene expression and its uniformity in response
to stress make these genes potential biomarkers for stress in trout.},
issn = {1050-4648},
keywords = {Gene expression, Confinement, Stress, Acute phase response},
url = {http://www.sciencedirect.com/science/article/B6WFN-4WGK4HT-2/2/9de28aea9f3afc00d569aa4ce5e1955f}
}
@ARTICLE{Talbot2009a,
author = {Talbot, Anita T. and Smith, Terry J. and Cairns, Michael T.},
title = {Characterisation of the differentially regulated trout protein 1
(DRTP1) gene in rainbow trout (Oncorhynchus mykiss)},
journal = {Fish \& Shellfish Immunology},
year = {2009},
volume = {26},
pages = {589--598},
number = {4},
month = apr,
issn = {1050-4648},
keywords = {Quantitative real-time PCR (qPCR), Promoter, Genome walking, Transfection,
Luciferase, Ly-6/uPAR},
url = {http://www.sciencedirect.com/science/article/B6WFN-4TKPVCV-1/2/eecd6555c1436955eb3f5f29dfe1597c}
}
@ARTICLE{Talbot2005,
author = {Talbot, Simon G. and Estilo, Cherry and Maghami, Ellie and Sarkaria,
Inderpal S. and Pham, Duy Khanh and O-charoenrat, Pornchai and Socci,
Nicholas D. and Ngai, Ivan and Carlson, Diane and Ghossein, Ronald
and Viale, Agnes and Park, Bernard J. and Rusch, Valerie W. and Singh,
Bhuvanesh},
title = {Gene Expression Profiling Allows Distinction between Primary and
Metastatic Squamous Cell Carcinomas in the Lung},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {3063--3071},
number = {8},
month = apr,
abstract = {Lung neoplasms commonly develop in patients previously treated for
head and neck carcinomas. The derivation of these tumors, either
as new primary lung cancers or as metastatic head and neck cancers,
is difficult to establish based on clinical or histopathologic criteria
since both are squamous cell carcinomas and have identical features
under light microscopy. However, this distinction has significant
treatment and prognostic implications. Gene expression profiling
was performed on a panel of 52 sequentially collected patients with
either primary lung (n = 21) or primary head and neck (n = 31) carcinomas
using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray.
Unsupervised hierarchical clustering with Ward linkage and the Pearson
correlation metric was performed. To assess robustness, bootstrap
resampling was performed with 1,000 iterations. A t test of the normalized
values for each gene was used to determine the genes responsible
for segregating head and neck from lung primary carcinomas, and those
with the most differential expression were used for later analyses.
In the absence of a large "test" set of tumors, we used a supervised
leave-one-out cross-validation to test how well we could predict
the tumor origin. Once a gene expression profile was established,
12 lung lesions taken from patients with previously treated head
and neck cancers were similarly analyzed by gene expression profiling
to determine their sites of origin. Unsupervised clustering analysis
separated the study cohort into two distinct groups which reliably
remained segregated with bootstrap resampling. Group 1 consisted
of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and
1 tongue carcinoma. The clustering was not changed even when normal
lung or tongue profiles were subtracted from the corresponding carcinomatous
lesions, and a leave-one-out cross-validation showed a 98% correct
prediction (see Supplementary Data 1). A minimum set of 500 genes
required to distinguish these groups was established. Given the ability
to segregate these lesions using molecular profiling, we analyzed
the lung tumors of undetermined origin. All cases clearly clustered
with either lung or tongue tumor subsets, strongly supporting our
hypothesis that this technique could elucidate the tissue of origin
of metastatic lesions. Although histologically similar, squamous
cell carcinomas have distinct gene expression profiles based on their
anatomic sites of origin. Accordingly, the application of gene expression
profiling may be useful in identifying the derivation of lung nodules
and consequently enhances treatment planning.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/8/3063}
}
@ARTICLE{Taleb2006,
author = {Taleb, S. and Van Haaften, R. and Henegar, C. and Hukshorn, C. and
Cancello, R. and Pelloux, V. and Hanczar, B. and Viguerie, N. and
Langin, D. and Evelo, C. and Zucker, J. and Clément, K. and Saris,
W. H. M.},
title = {Microarray profiling of human white adipose tissue after exogenous
leptin injection},
journal = {European Journal of Clinical Investigation},
year = {2006},
volume = {36},
pages = {153--163},
number = {3},
abstract = {Abstract Background  Leptin is a secreted adipocyte hormone that
plays a key role in the regulation of body weight homeostasis. The
leptin effect on human white adipose tissue (WAT) is still debated.
Objective  The aim of this study was to assess whether the administration
of polyethylene glycol-leptin (PEG-OB) in a single supraphysiological
dose has transcriptional effects on genes of WAT and to identify
its target genes and functional pathways in WAT. Materials and methods 
Blood samples and WAT biopsies were obtained from 10 healthy nonobese
men before treatment and 72Â h after the PEG-OB injection, leading
to an approximate 809-fold increase in circulating leptin. The WAT
gene expression profile before and after the PEG-OB injection was
compared using pangenomic microarrays. Functional gene annotations
based on the gene ontology of the PEG-OB regulated genes were performed
using both an ‘in house’ automated procedure and GenMAPP (Gene
Microarray Pathway Profiler), designed for viewing and analyzing
gene expression data in the context of biological pathways. Results 
Statistical analysis of microarray data revealed that PEG-OB had
a major down-regulated effect on WAT gene expression, as we obtained
1822 and 100 down- and up-regulated genes, respectively. Microarray
data were validated using reverse transcription quantitative PCR.
Functional gene annotations of PEG-OB regulated genes revealed that
the functional class related to immunity and inflammation was among
the most mobilized PEG-OB pathway in WAT. These genes are mainly
expressed in the cell of the stroma vascular fraction in comparison
with adipocytes. Conclusion  Our observations support the hypothesis
that leptin could act on WAT, particularly on genes related to inflammation
and immunity, which may suggest a novel leptin target pathway in
human WAT.},
issn = {1365-2362},
keywords = {Adipose tissue, inflammation and gene profiling, PEG-OB},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2362.2006.01614.x}
}
@ARTICLE{Talebizadeh2008,
author = {Talebizadeh, Zohreh and Butler, Merlin G. and Theodoro, Mariana F.},
title = {Feasibility and relevance of examining lymphoblastoid cell lines
to study role of microRNAs in autism},
journal = {Autism Res},
year = {2008},
volume = {1},
pages = {240--250},
number = {4},
abstract = {Abstract 10.1002/aur.33.abs To assess the feasibility and relevance
of using lymphoblastoid cell lines to study the role of noncoding
RNAs in the etiology of autism, we evaluated global expression profiling
of 470 mature human microRNAs from six subjects with autism compared
with six matched controls. Differential expression (either higher
or lower) for 9 of the 470 microRNAs was observed in our autism samples
compared with controls. Potential target genes for these microRNAs
were identified using computer tools, which included several autism
susceptibility genes. Our preliminary results indicate microRNAs
should be considered and evaluated in the etiology of autism. In
addition, analysis of this class of noncoding RNAs in lymphoblastoid
cells has the potential to reveal at least a subset of brain-related
microRNAs implicated in autism. Subsequently, this model system should
allow for detection of complex subtle changes in susceptibility genes/pathways
contributing to autism.},
issn = {1939-3806},
keywords = {microRNA, autism, lymphoblastoid cell lines, differential expression},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/aur.33}
}
@ARTICLE{Taliaferro2011,
author = {Taliaferro, J. Matthew and Alvarez, Nehemiah and Green, Richard E.
and Blanchette, Marco and Rio, Donald C.},
title = {Evolution of a tissue-specific splicing network},
journal = {Genes \& Dev.},
year = {2011},
volume = {25},
pages = {608--620},
number = {6},
month = mar,
abstract = {Alternative splicing of precursor mRNA (pre-mRNA) is a strategy employed
by most eukaryotes to increase transcript and proteomic diversity.
Many metazoan splicing factors are members of multigene families,
with each member having different functions. How these highly related
proteins evolve unique properties has been unclear. Here we characterize
the evolution and function of a new Drosophila splicing factor, termed
LS2 (Large Subunit 2), that arose from a gene duplication event of
dU2AF50, the large subunit of the highly conserved heterodimeric
general splicing factor U2AF (U2-associated factor). The quickly
evolving LS2 gene has diverged from the splicing-promoting, ubiquitously
expressed dU2AF50 such that it binds a markedly different RNA sequence,
acts as a splicing repressor, and is preferentially expressed in
testes. Target transcripts of LS2 are also enriched for performing
testes-related functions. We therefore propose a path for the evolution
of a new splicing factor in Drosophila that regulates specific pre-mRNAs
and contributes to transcript diversity in a tissue-specific manner.},
comment = {10.1101/gad.2009011},
url = {http://genesdev.cshlp.org/cgi/content/abstract/25/6/608}
}
@ARTICLE{Taliercio2009,
author = {Taliercio, Earl and Romano, Gabriela and Scheffler, Jodi and Ayre,
Brian},
title = {Expression of genes associated with carbohydrate metabolism in cotton
stems and roots},
journal = {BMC Plant Biology},
year = {2009},
volume = {9},
pages = {11},
number = {1},
abstract = {BACKGROUND:Cotton (Gossypium hirsutum L) is an important crop worldwide
that provides fiber for the textile industry. Cotton is a perennial
plant that stores starch in stems and roots to provide carbohydrates
for growth in subsequent seasons. Domesticated cotton makes these
reserves available to developing seeds which impacts seed yield.
The goals of these analyses were to identify genes and physiological
pathways that establish cotton stems and roots as physiological sinks
and investigate the role these pathways play in cotton development
during seed set.RESULTS:Analysis of field-grown cotton plants indicated
that starch levels peaked about the time of first anthesis and then
declined similar to reports in greenhouse-grown cotton plants. Starch
accumulated along the length of the stem and the shape and size of
the starch grains from stems were easily distinguished from transient
starch. Microarray analyses compared gene expression in tissues containing
low levels of starch with tissues rapidly accumulating starch. Statistical
analysis of differentially expressed genes indicated increased expression
among genes associated with starch synthesis, starch degradation,
hexose metabolism, raffinose synthesis and trehalose synthesis. The
anticipated changes in these sugars were largely confirmed by measuring
soluble sugars in selected tissues.CONCLUSION:In domesticated cotton
starch stored prior to flowering was available to support seed production.
Starch accumulation observed in young field-grown plants was not
observed in greenhouse grown plants. A suite of genes associated
with starch biosynthesis was identified. The pathway for starch utilization
after flowering was associated with an increase in expression of
a glucan water dikinase gene as has been implicated in utilization
of transient starch. Changes in raffinose levels and levels of expression
of genes controlling trehalose and raffinose biosynthesis were also
observed in vegetative cotton tissues as plants age.},
doi = {10.1186/1471-2229-9-11},
issn = {1471-2229},
pubmedid = {19161628},
url = {http://www.biomedcentral.com/1471-2229/9/11}
}
@ARTICLE{Talkowski2011,
author = {Talkowski, Michael E. and Ernst, Carl and Heilbut, Adrian and Chiang,
Colby and Hanscom, Carrie and Lindgren, Amelia and Kirby, Andrew
and Liu, Shangtao and Muddukrishna, Bhavana and Ohsumi, Toshiro K.
and Shen, Yiping and Borowsky, Mark and Daly, Mark J. and Morton,
Cynthia C. and Gusella, James F.},
title = {Next-Generation Sequencing Strategies Enable Routine Detection of
Balanced Chromosome Rearrangements for Clinical Diagnostics and Genetic
Research},
journal = {The American Journal of Human Genetics},
year = {2011},
volume = {88},
pages = {469--481},
number = {4},
month = apr,
abstract = {The contribution of balanced chromosomal rearrangements to complex
disorders remains unclear because they are not detected routinely
by genome-wide microarrays and clinical localization is imprecise.
Failure to consider these events bypasses a potentially powerful
complement to single nucleotide polymorphism and copy-number association
approaches to complex disorders, where much of the heritability remains
unexplained. To capitalize on this genetic resource, we have applied
optimized sequencing and analysis strategies to test whether these
potentially high-impact variants can be mapped at reasonable cost
and throughput. By using a whole-genome multiplexing strategy, rearrangement
breakpoints could be delineated at a fraction of the cost of standard
sequencing. For rearrangements already mapped regionally by karyotyping
and fluorescence in situ hybridization, a targeted approach enabled
capture and sequencing of multiple breakpoints simultaneously. Importantly,
this strategy permitted capture and unique alignment of up to 97%
of repeat-masked sequences in the targeted regions. Genome-wide analyses
estimate that only 3.7% of bases should be routinely omitted from
genomic DNA capture experiments. Illustrating the power of these
approaches, the rearrangement breakpoints were rapidly defined to
base pair resolution and revealed unexpected sequence complexity,
such as co-occurrence of inversion and translocation as an underlying
feature of karyotypically balanced alterations. These findings have
implications ranging from genome annotation to de novo assemblies
and could enable sequencing screens for structural variations at
a cost comparable to that of microarrays in standard clinical practice.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S0002929711001054}
}
@ARTICLE{Tallant2005,
author = {Tallant, E. Ann and Ferrario, Carlos M. and Gallagher, Patricia E.},
title = {Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation
of the mas receptor},
journal = {Am J Physiol Heart Circ Physiol},
year = {2005},
volume = {289},
pages = {H1560--1566},
number = {4},
month = oct,
abstract = {Peptide hormones such as ANG II and endothelin contribute to cardiac
remodeling after myocardial infarction by stimulating myocyte hypertrophy
and myofibroblast proliferation. In contrast, angiotensin-(1-7) [ANG-(1-7)]
infusion after myocardial infarction reduced myocyte size and attenuated
ventricular dysfunction and remodeling. We measured the effect of
ANG-(1-7) on protein and DNA synthesis in cultured neonatal rat myocytes
to assess the role of the heptapeptide in cell growth. ANG-(1-7)
significantly attenuated either fetal bovine serum- or endothelin-1-stimulated
[3H]leucine incorporation into myocytes with no effect on [3H]thymidine
incorporation. [D-Ala7]-ANG-(1-7), the selective ANG type 1-7 (AT1-7)
receptor antagonist, blocked the ANG-(1-7)-mediated reduction in
protein synthesis in cardiac myocytes, whereas the AT1 and AT2 angiotensin
peptide receptors were ineffective. Serum-stimulated ERK1/ERK2 mitogen-activated
protein kinase activity was significantly decreased by ANG-(1-7)
in myocytes, a response that was also blocked by [D-Ala7]-ANG-(1-7).
Both rat heart and cardiac myocytes express the mRNA for the mas
receptor, and a 59-kDa immunoreactive protein was identified in both
extracts of rat heart and cultured myocytes by Western blot hybridization
with the use of an antibody to mas, an ANG-(1-7) receptor. Transfection
of cultured myocytes with an antisense oligonucleotide to the mas
receptor blocked the ANG-(1-7)-mediated inhibition of serum-stimulated
MAPK activation, whereas a sense oligonucleotide was ineffective.
These results suggest that ANG-(1-7) reduces the growth of cardiomyocytes
through activation of the mas receptor. Because ANG-(1-7) is elevated
after treatment with angiotensin-converting enzyme inhibitors or
AT1 receptor blockers, ANG-(1-7) may contribute to their beneficial
effects on cardiac dysfunction and ventricular remodeling after myocardial
infarction.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/289/4/H1560}
}
@ARTICLE{Tam2006,
author = {Tam, Le Thi and Eymann, Christine and Albrecht, Dirk and Sietmann,
Rabea and Schauer, Frieder and Hecker, Michael and Antelmann, Haike},
title = {Differential gene expression in response to phenol and catechol reveals
different metabolic activities for the degradation of aromatic compounds
in Bacillus subtilis},
journal = {Environmental Microbiology},
year = {2006},
volume = {8},
pages = {1408--1427},
number = {8},
abstract = {Summary Aromatic organic compounds that are present in the environment
can have toxic effects or provide carbon sources for bacteria. We
report here the global response of Bacillus subtilis 168 to phenol
and catechol using proteome and transcriptome analyses. Phenol induced
the HrcA, σB and CtsR heat-shock regulons as well as the Spx disulfide
stress regulon. Catechol caused the activation of the HrcA and CtsR
heat-shock regulons and a thiol-specific oxidative stress response
involving the Spx, PerR and FurR regulons but no induction of the
σB regulon. The most surprising result was that several catabolite-controlled
genes are derepressed by catechol, even if glucose is taken up under
these conditions. This derepression of the carbon catabolite control
was dependent on the glucose concentration in the medium, as glucose
excess increased the derepression of the CcpA-dependent lichenin
utilization licBCAH operon and the ribose metabolism rbsRKDACB operon
by catechol. Growth and viability experiments with catechol as sole
carbon source suggested that B. subtilis is not able to utilize
catechol as a carbon-energy source. In addition, the microarray results
revealed the very strong induction of the yfiDE operon by catechol
of which the yfiE gene shares similarities to glyoxalases/bleomycin
resistance proteins/extradiol dioxygenases. Using recombinant His6-YfiEBs
we demonstrate that YfiE shows catechol-2,3-dioxygenase activity
in the presence of catechol as the metabolite 2-hydroxymuconic semialdehyde
was measured. Furthermore, both genes of the yfiDE operon are essential
for the growth and viability of B. subtilis in the presence of catechol.
Thus, our studies revealed that the catechol-2,3-dioxygenase YfiE
is the key enzyme of a meta cleavage pathway in B. subtilis involved
in the catabolism of catechol.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2006.01034.x}
}
@ARTICLE{Tam2010,
author = {Tam, Vincent H. and Chang, Kai-Tai and Abdelraouf, Kamilia and Brioso,
Cristina G. and Ameka, Magdalene and McCaskey, Laurie A. and Weston,
Jaye S. and Caeiro, Juan-Pablo and Garey, Kevin W.},
title = {Prevalence, Resistance Mechanisms, and Susceptibility of Multidrug-Resistant
Bloodstream Isolates of Pseudomonas aeruginosa},
journal = {Antimicrob. Agents Chemother.},
year = {2010},
volume = {54},
pages = {1160--1164},
number = {3},
month = mar,
abstract = {Pseudomonas aeruginosa is an important pathogen commonly implicated
in nosocomial infections. The occurrence of multidrug-resistant (MDR)
P. aeruginosa strains is increasing worldwide and limiting our therapeutic
options. The MDR phenotype can be mediated by a variety of resistance
mechanisms, and the corresponding relative biofitness is not well
established. We examined the prevalence, resistance mechanisms, and
susceptibility of MDR P. aeruginosa isolates (resistant to [≥]3
classes of antipseudomonal agents [penicillins/cephalosporins, carbapenems,
quinolones, and aminoglycosides]) obtained from a large, university-affiliated
hospital. Among 235 nonrepeat bloodstream isolates screened between
2005 and 2007, 33 isolates (from 20 unique patients) were found to
be MDR (crude prevalence rate, 14%). All isolates were resistant
to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins,
and 21% were resistant to the aminoglycosides. By using the first
available isolate for each bacteremia episode (n = 18), 13 distinct
clones were revealed by repetitive-element-based PCR. Western blotting
revealed eight isolates (44%) to have MexB overexpression. Production
of a carbapenemase (VIM-2) was found in one isolate, and mutations
in gyrA (T83I) and parC (S87L) were commonly found. Growth rates
of most MDR isolates were similar to that of the wild type, and two
isolates (11%) were found to be hypermutable. All available isolates
were susceptible to polymyxin B, and only one isolate was nonsusceptible
to colistin (MIC, 3 mg/liter), but all isolates were nonsusceptible
to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring
of the prevalence and resistance mechanisms of MDR P. aeruginosa
would enable us to formulate rational treatment strategies to combat
nosocomial infections.},
url = {http://aac.asm.org/cgi/content/abstract/54/3/1160}
}
@ARTICLE{Tam2007,
author = {Tam, Vincent H. and Chang, Kai-Tai and LaRocco, Mark T. and Schilling,
Amy N. and McCauley, Shana K. and Poole, Keith and Garey, Kevin W.},
title = {Prevalence, mechanisms, and risk factors of carbapenem resistance
in bloodstream isolates of Pseudomonas aeruginosa},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2007},
volume = {58},
pages = {309--314},
number = {3},
month = jul,
abstract = {We examined the prevalence of various carbapenem resistance mechanisms
in Pseudomonas aeruginosa bloodstream isolates from a university-affiliated
hospital. Isolates obtained in 2003 and 2004 were screened for meropenem/imipenem
resistance, and clonality was assessed by repetitive-element-based
polymerase chain reaction. The presence of carbapenemase and AmpC
overexpression was ascertained by spectrophotometric assays. Outer
membrane protein profiles were examined by sodium dodecyl sulfate
polyacrylamide gel electrophoresis, and efflux pump overexpression
was confirmed by Western blotting. We examined 129 nonrepeat isolates;
21 isolates (from 13 distinct clones) were resistant to meropenem
or imipenem (prevalence rate = 16.3%). Nineteen (90.5%) carbapenem-resistant
isolates had reduced OprD expression, and 6 (28.6%) isolates had
overexpression of MexB. Increased length of hospital stay was identified
as a significant risk factor for bacteremia due to carbapenem-resistant
P. aeruginosa. Understanding the prevalence and mechanism of carbapenem
resistance in P. aeruginosa may guide empiric therapy for nosocomial
infections in our hospital.},
issn = {0732-8893},
keywords = {Pseudomonas aeruginosa, Bloodstream infection, Carbapenem resistance,
Prevalence},
url = {http://www.sciencedirect.com/science/article/B6T60-4P48RC8-3/2/2d61d19c92cc8c8097a79f580adb0fed}
}
@ARTICLE{Tam2009,
author = {Tam, Vincent H. and Chang, Kai-Tai and Schilling, Amy N. and LaRocco,
Mark T. and Genty, Layne O. and Garey, Kevin W.},
title = {Impact of AmpC overexpression on outcomes of patients with Pseudomonas
aeruginosa bacteremia},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2009},
volume = {63},
pages = {279--285},
number = {3},
month = mar,
abstract = {AmpC overexpression (AmpC++) is a significant mechanism of [beta]-lactam
resistance in Pseudomonas aeruginosa, but its impact on clinical
outcomes is not well established. To examine the influence of AmpC++
on clinical outcomes of patients with P. aeruginosa bacteremia, we
screened all bloodstream P. aeruginosa isolates obtained from 2003
to 2006 for AmpC++. Demographics and outcomes were retrospectively
compared between patients with P. aeruginosa bacteremia caused by
AmpC++ and pan-susceptible strains (wild-type controls). Of the 263
isolates screened, 63 (24.0%) were nonsusceptible to ceftazidime.
Clinical data of 42 AmpC++ isolates from 21 patients were compared
with 33 control patients. The 2 groups were similar in sex and race.
Patients in the AmpC++ group was more likely to receive inappropriate
empiric antibiotics (odds ratio [OR] = 67.5; 95% confidence interval
[CI], 6.3-720.0) and experience microbiologic persistence (OR = 12.2;
95% CI, 1.7-87.7). In institutions with a high prevalence of AmpC++,
empiric therapy with agents with activity against AmpC++ strains
may be warranted.},
issn = {0732-8893},
keywords = {AmpC overexpression, Pseudomonas aeruginosa, Outcomes},
url = {http://www.sciencedirect.com/science/article/B6T60-4VB559T-1/2/e5f0266c8f76a2f1cb6fdd80b5463ff8}
}
@ARTICLE{Tam2010a,
author = {Tam, Vincent H. and Rogers, Cary A. and Chang, Kai-Tai and Weston,
Jaye S. and Caeiro, Juan-Pablo and Garey, Kevin W.},
title = {Impact of Multidrug-Resistant Pseudomonas aeruginosa Bacteremia on
Patient Outcomes},
journal = {Antimicrob. Agents Chemother.},
year = {2010},
volume = {54},
pages = {3717--3722},
number = {9},
month = sep,
abstract = {Trends of rising rates of resistance in Pseudomonas aeruginosa make
selection of appropriate empirical therapy increasingly difficult,
but whether multidrug-resistant (MDR) P. aeruginosa is associated
with worse clinical outcomes is not well established. The objective
of this study was to determine the impact of MDR (resistance to three
or more classes of antipseudomonal agents) P. aeruginosa bacteremia
on patient outcomes. We performed a retrospective cohort study of
adult patients with P. aeruginosa bacteremia from 2005 to 2008. Patients
were identified by the microbiology laboratory database, and pertinent
clinical data were collected. Logistic regression was used to explore
independent risk factors for 30-day mortality. Classification and
regression tree analysis was used to determine threshold breakpoints
for continuous variables. Kaplan-Meier survival analysis was used
to compare time to mortality, after normalization of the patients'
underlying risks by propensity scoring. A total of 109 bacteremia
episodes were identified; 25 episodes (22.9%) were caused by MDR
P. aeruginosa. Patients with MDR P. aeruginosa bacteremia were more
likely to receive inappropriate empirical therapy (44.0% and 6.0%,
respectively; P < 0.001) and had longer prior hospital stays (32.6
{+/-} 37.3 and 14.4 {+/-} 43.6 days, respectively; P = 0.046). Multivariate
regression revealed that 30-day mortality was associated with multidrug
resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9
to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an
APACHE II score of [≥]22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time
to mortality was also shorter in the MDR cohort (P = 0.011). Multidrug
resistance is a significant risk factor for 30-day mortality in patients
with P. aeruginosa bacteremia; efforts to curb the spread of MDR
P. aeruginosa could be beneficial.},
url = {http://aac.asm.org/cgi/content/abstract/54/9/3717}
}
@ARTICLE{Tamaoki2009,
author = {Tamaoki, D. and Karahara, I. and Nishiuchi, T. and De Oliveira, S.
and Schreiber, L. and Wakasugi, T. and Yamada, K. and Yamaguchi,
K. and Kamisaka, S.},
title = {Transcriptome profiling in Arabidopsis inflorescence stems grown
under hypergravity in terms of cell walls and plant hormones},
journal = {Advances in Space Research},
year = {2009},
volume = {44},
pages = {245--253},
number = {2},
month = jul,
abstract = {Land plants rely on lignified secondary cell walls in supporting their
body weight on the Earth. Although gravity influences the formation
of the secondary cell walls, the regulatory mechanism of their formation
by gravity is not yet understood. We carried out a comprehensive
analysis of gene expression in inflorescence stems of Arabidopsis
thaliana L. using microarray (22 K) to identify genes whose expression
is modulated under hypergravity condition (300 g). Total RNA was
isolated from the basal region of inflorescence stems of plants grown
for 24 h at 300 g or 1 g. Microarray analysis showed that hypergravity
up-regulated the expression of 403 genes to more than 2-fold. Hypergravity
up-regulated the genes responsible for the biosynthesis or modification
of cell wall components such as lignin, xyloglucan, pectin and structural
proteins. In addition, hypergravity altered the expression of genes
related to the biosynthesis of plant hormones such as auxin and ethylene
and that of genes encoding hormone-responsive proteins. Our transcriptome
profiling indicates that hypergravity influences the formation of
secondary cell walls by modulating the pattern of gene expression,
and that auxin and/or ethylene play an important role in signaling
hypergravity stimulus.},
booktitle = {Life Sciences in Space},
issn = {0273-1177},
keywords = {Arabidopsis, Auxin, Cell wall, Hypergravity, Lignin, Microarray},
url = {http://www.sciencedirect.com/science/article/B6V3S-4VXTSRH-1/2/cbdfdd411cd23792aa07e4402052e7a9}
}
@ARTICLE{Tamasi2009,
author = {Tamasi, Viola and Juvan, Peter and Beer, Markus and Rozman, Damjana
and Meyer, Urs A.},
title = {Transcriptional Activation of PPARa by Phenobarbital in the Absence
of CAR and PXR},
journal = {Molecular Pharmaceutics},
year = {2009},
volume = {6},
pages = {1573-1581},
number = {5},
note = {PMID: 19708687},
doi = {10.1021/mp9001552},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/mp9001552},
url = {http://pubs.acs.org/doi/abs/10.1021/mp9001552}
}
@ARTICLE{Tamguney2009,
author = {Tamguney, Gultekin and Francis, Kevin P. and Giles, Kurt and Lemus,
Azucena and DeArmond, Stephen J. and Prusiner, Stanley B.},
title = {Measuring prions by bioluminescence imaging},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {15002--15006},
number = {35},
month = sep,
abstract = {Prions are infectious proteins that cause fatal neurodegenerative
diseases. Because astrocytic gliosis marked by the deposition of
fibrils composed of GFAP is a prominent feature of prion disease,
we asked whether GFAP might be used as a surrogate marker for prions.
To interrogate this posit, we inoculated prions into transgenic (Tg)
mice expressing luciferase (luc) under the GFAP gene (Gfap) promoter,
denoted Tg(Gfap-luc) mice. Weekly noninvasive, bioluminescence imaging
(BLI) detected an increase in light emitted from the brains of Tg(Gfap-luc)
mice at {approx}55 d after inoculation and {approx}62 d before neurologic
deficits appeared. To determine whether BLI could be used as a proxy
bioassay for prion infectivity, we performed endpoint titrations
of prions in Tg(Gfap-luc) mice. BLI bioassays were as or more sensitive
than those determined by the onset of neurological dysfunction, and
were completed in approximately half the time. Our studies argue
that BLI is likely to be a suitable surrogate for measuring prion
infectivity, and might be useful in the study of Tg mouse models
for other neurodegenerative illnesses.},
url = {http://www.pnas.org/cgi/content/abstract/106/35/15002}
}
@ARTICLE{Tamiya2005,
author = {Tamiya, Gen and Shinya, Minori and Imanishi, Tadashi and Ikuta, Tomoki
and Makino, Satoshi and Okamoto, Koichi and Furugaki, Koh and Matsumoto,
Toshiko and Mano, Shuhei and Ando, Satoshi and Nozaki, Yasuyuki and
Yukawa, Wataru and Nakashige, Ryo and Yamaguchi, Daisuke and Ishibashi,
Hideo and Yonekura, Manabu and Nakami, Yuu and Takayama, Seiken and
Endo, Takaho and Saruwatari, Takuya and Yagura, Masaru and Yoshikawa,
Yoko and Fujimoto, Kei and Oka, Akira and Chiku, Suenori and Linsen,
Samuel E.V. and Giphart, Marius J. and Kulski, Jerzy K. and Fukazawa,
Toru and Hashimoto, Hiroshi and Kimura, Minoru and Hoshina, Yuuichi
and Suzuki, Yasuo and Hotta, Tomomitsu and Mochida, Joji and Minezaki,
Takatoshi and Komai, Koichiro and Shiozawa, Shunichi and Taniguchi,
Atsuo and Yamanaka, Hisashi and Kamatani, Naoyuki and Gojobori, Takashi
and Bahram, Seiamak and Inoko, Hidetoshi},
title = {Whole genome association study of rheumatoid arthritis using 27 039
microsatellites},
journal = {Hum. Mol. Genet.},
year = {2005},
volume = {14},
pages = {2305--2321},
number = {16},
month = aug,
abstract = {A major goal of current human genome-wide studies is to identify the
genetic basis of complex disorders. However, the availability of
an unbiased, reliable, cost efficient and comprehensive methodology
to analyze the entire genome for complex disease association is still
largely lacking or problematic. Therefore, we have developed a practical
and efficient strategy for whole genome association studies of complex
diseases by charting the human genome at 100 kb intervals using a
collection of 27 039 microsatellites and the DNA pooling method in
three successive genomic screens of independent case-control populations.
The final step in our methodology consists of fine mapping of the
candidate susceptible DNA regions by single nucleotide polymorphisms
(SNPs) analysis. This approach was validated upon application to
rheumatoid arthritis, a destructive joint disease affecting up to
1% of the population. A total of 47 candidate regions were identified.
The top seven loci, withstanding the most stringent statistical tests,
were dissected down to individual genes and/or SNPs on four chromosomes,
including the previously known 6p21.3-encoded Major Histocompatibility
Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association
analysis complemented by end stage SNP typing provides a new tool
for genetic dissection of multifactorial pathologies including common
diseases.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/14/16/2305}
}
@ARTICLE{Tamplin2011,
author = {Owen J. Tamplin and Brian J. Cox and Janet Rossant},
title = {Integrated microarray and ChIP analysis identifies multiple Foxa2
dependent target genes in the notochord},
journal = {Developmental Biology},
year = {2011},
volume = {360},
pages = {415 - 425},
number = {2},
abstract = {The node and notochord are key tissues required for patterning of
the vertebrate body plan. Understanding the gene regulatory network
that drives their formation and function is therefore important.
Foxa2 is a key transcription factor at the top of this genetic hierarchy
and finding its targets will help us to better understand node and
notochord development. We performed an extensive microarray-based
gene expression screen using sorted embryonic notochord cells to
identify early notochord-enriched genes. We validated their specificity
to the node and notochord by whole mount in situ hybridization. This
provides the largest available resource of notochord-expressed genes,
and therefore candidate Foxa2 target genes in the notochord. Using
existing Foxa2 ChIP-seq data from adult liver, we were able to identify
a set of genes expressed in the notochord that had associated regions
of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription
factor, we reasoned that these sites might represent notochord-specific
enhancers. Candidate Foxa2-bound regions were tested for notochord
specific enhancer function in a zebrafish reporter assay and 7 novel
notochord enhancers were identified. Importantly, sequence conservation
or predictive models could not have readily identified these regions.
Mutation of putative Foxa2 binding elements in two of these novel
enhancers abrogated reporter expression and confirmed their Foxa2
dependence. The combination of highly specific gene expression profiling
and genome-wide ChIP analysis is a powerful means of understanding
developmental pathways, even for small cell populations such as the
notochord.},
doi = {10.1016/j.ydbio.2011.10.002},
issn = {0012-1606},
keywords = {Noto},
url = {http://www.sciencedirect.com/science/article/pii/S0012160611012978}
}
@ARTICLE{Tan2008,
author = {Tan, Benita K.T. and Tan, Lay Keng and Yu, Kun and Tan, Puay Hoon
and Lee, Ming and Sii, Lang Hiong and Wong, Chow Yin and Ho, Gay
Hui and Yeo, Allen W.Y. and Chow, Pierce K.H. and Koong, Heng Nung
and Yong, Wei Sean and Lim, Dennis T.H. and Ooi, London L.P.J. and
Soo, Khee Chee and Tan, Patrick},
title = {Clinical Validation of a Customized Multiple Signature Microarray
for Breast Cancer},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {461--469},
number = {2},
month = jan,
abstract = {Purpose: Current histopathologic systems for classifying breast tumors
require evaluation of multiple variables and are often associated
with significant interobserver variability. Recent studies suggest
that gene expression profiles may represent a promising alternative
for clinical cancer classification. Here, we investigated the use
of a customized microarray as a potential tool for clinical practice.
Experimental Design: We fabricated custom 188-gene microarrays containing
expression signatures for three breast cancer molecular subtypes
[luminal/estrogen receptor (ER) positive, human epidermal growth
factor receptor 2 (HER2), and "basaloid"], the Nottingham prognostic
index (NPI-ES), and low histologic grade (TuM1). The reliability
of these multiple-signature arrays (MSA) was tested in a prospective
cohort of 165 patients with primary breast cancer. Results: The MSA-ER
signature exhibited a high concordance of 90% with ER immunohistochemistry
reported on diagnosis (P < 0.001). This remained unchanged at 89%
(P < 0.001) when the immunohistochemistry was repeated using current
laboratory standards. Expression of the HER2 signature showed a good
correlation of 76% with HER2 fluorescence in situ hybridization (FISH;
ratio [≥]2.2; P < 0.001), which further improved to 89% when the
ratio cutoff was raised to [≥]5. A proportion of low-level FISH-amplified
samples (ratio, 2.2-5) behaved comparably to FISH-negative samples
by HER2 signature expression, HER2 quantitative reverse transcription-PCR,
and HER2 immunohistochemistry. Luminal/ER+ tumors with high NPI-ES
expression were associated with high NPI scores (P = 0.001), and
luminal/ER+ TuM1-expressing tumors were significantly correlated
with low histologic grade (P = 0.002) and improved survival outcome
in an interim analysis (hazard ratio, 0.2; P = 0.019). Conclusion:
The consistency of the MSA platform in an independent patient population
suggests that custom microarrays could potentially function as an
adjunct to standard immunohistochemistry and FISH in clinical practice.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/2/461}
}
@ARTICLE{Tan2009,
author = {Tan, David S.P. and Lambros, Maryou B.K. and Rayter, Sydonia and
Natrajan, Rachael and Vatcheva, Radost and Gao, Qiong and Marchio,
Caterina and Geyer, Felipe C. and Savage, Kay and Parry, Suzanne
and Fenwick, Kerry and Tamber, Narinder and Mackay, Alan and Dexter,
Tim and Jameson, Charles and McCluggage, W. Glenn and Williams, Alistair
and Graham, Ashley and Faratian, Dana and El-Bahrawy, Mona and Paige,
Adam J. and Gabra, Hani and Gore, Martin E. and Zvelebil, Marketa
and Lord, Christopher J. and Kaye, Stanley B. and Ashworth, Alan
and Reis-Filho, Jorge S.},
title = {PPM1D Is a Potential Therapeutic Target in Ovarian Clear Cell Carcinomas},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {2269--2280},
number = {7},
month = apr,
abstract = {Purpose: To identify therapeutic targets in ovarian clear cell carcinomas,
a chemoresistant and aggressive type of ovarian cancer. Experimental
Design: Twelve ovarian clear cell carcinoma cell lines were subjected
to tiling path microarray comparative genomic hybridization and genome-wide
expression profiling analysis. Regions of high-level amplification
were defined and genes whose expression levels were determined by
copy number and correlated with gene amplification were identified.
The effects of inhibition of PPM1D were assessed using short hairpin
RNA constructs and a small-molecule inhibitor (CCT007093). The prevalence
of PPM1D amplification and mRNA expression was determined using chromogenic
in situ hybridization and quantitative real-time reverse transcription-PCR
in a cohort of pure ovarian clear cell carcinomas and on an independent
series of unselected epithelial ovarian cancers. Results: Array-based
comparative genomic hybridization analysis revealed regions of high-level
amplification on 1q32, 1q42, 2q11, 3q24-q26, 5p15, 7p21-p22, 11q13.2-q13.4,
11q22, 17q21-q22, 17q23.2, 19q12-q13, and 20q13.2. Thirty-four genes
mapping to these regions displayed expression levels that correlated
with copy number gains/amplification. PPM1D had significantly higher
levels of mRNA expression in ovarian clear cell carcinoma cell lines
harboring gains/amplifications of 17q23.2. PPM1D inhibition revealed
that PPM1D expression and phosphatase activity are selectively required
for the survival of ovarian clear cell carcinoma cell lines with
17q23.2 amplification. PPM1D amplification was significantly associated
with ovarian clear cell carcinoma histology (P = 0.0003) and found
in 10% of primary ovarian clear cell carcinomas. PPM1D expression
levels were significantly correlated with PPM1D gene amplification
in primary ovarian clear cell carcinomas. Conclusion: Our data provide
strong circumstantial evidence that PPM1D is a potential therapeutic
target for a subgroup of ovarian clear cell carcinomas.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/7/2269}
}
@ARTICLE{Tan2010a,
author = {Tan, E.-H. and Ramlau, R. and Pluzanska, A. and Kuo, H.-P. and Reck,
M. and Milanowski, J. and Au, J. S.-K. and Felip, E. and Yang, P.-C.
and Damyanov, D. and Orlov, S. and Akimov, M. and Delmar, P. and
Essioux, L. and Hillenbach, C. and Klughammer, B. and McLoughlin,
P. and Baselga, J.},
title = {A multicentre phase II gene expression profiling study of putative
relationships between tumour biomarkers and clinical response with
erlotinib in non-small-cell lung cancer},
journal = {Annals of Oncology},
year = {2010},
volume = {21},
pages = {217--222},
number = {2},
month = feb,
abstract = {Background: Identification of appropriate markers for predicting clinical
benefit with erlotinib in non-small-cell lung cancer (NSCLC) may
be able to guide patient selection for treatment. This open-label,
multicentre, phase II trial aimed to identify genes with potential
use as biomarkers for clinical benefit from erlotinib therapy.Methods:
Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy
regimen had failed were treated with erlotinib (150 mg/day). Tumour
biopsies were analysed using gene expression profiling with Affymetrix
GeneChip® microarrays. Differentially expressed genes were verified
using quantitative RT–PCR (qRT–PCR).Results: A total of 264 patients
were enrolled in the study. Gene expression profiles found no statistically
significant differentially expressed genes between patients with
and without clinical benefit. In an exploratory analysis in responding
versus nonresponding patients, three genes on chromosome 7 were expressed
at higher levels in the responding group [epidermal growth factor
receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine
nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification
using qRT–PCR validated the association between EGFR and PSPH overexpression,
but not RAPGEF5 overexpression, and clinical outcome.Conclusions:
This study supports the use of erlotinib as an alternative to chemotherapy
for patients with relapsed advanced NSCLC. Genetic amplification
of the EGFR region of chromosome 7 may be associated with response
to erlotinib therapy.},
url = {http://annonc.oxfordjournals.org/content/21/2/217.abstract}
}
@ARTICLE{Tan2011,
author = {Tan, Fei and Naciri, Mariam and Al-Rubeai, Mohamed},
title = {Osteoconductivity and growth factor production by MG63 osteoblastic
cells on bioglass-coated orthopedic implants},
journal = {Biotechnology and Bioengineering},
year = {2011},
volume = {108},
pages = {454--464},
number = {2},
abstract = {Abstract We have produced Bioglass coatings for Orthopedic implants
by using a novel coating technique, CoBlast. The two resultant surfaces,
designated BG and hydroxyapatite (HA)/BG, were compared with their
HA counterpart, OsteoZip in terms of osteoblastic cell attachment,
adhesion, proliferation, differentiation, and growth factor production.
BG and HA/BG were demonstrated by goniometry to be more hydrophilic
than OsteoZip. This corresponded to enhanced protein adsorption,
cell attachment, and cell adhesion documented by both quantitative
and qualitative assessments. BG and HA/BG surfaces had a significant
initial release of Si and Ca ions, and this was consistent with elevated
cell proliferation and basic fibroblast growth factor levels. However,
OsteoZip, being similar to HA/BG, exhibited better osteogenic differentiation
than BG did, shown by augmented differentiation marker activity at
both protein and mRNA levels. Sandwich ELISA was used to quantify
angiopoietin and inducible nitric oxide synthase which are involved
in peri-prosthetic angiogenesis and aseptic loosening of total hip
replacement, respectively. Both Bioglass-derived coatings provide
superior initial osteoconductivity to OsteoZip, and HA/Bioglass composite
coating outruns in long-term osteogenic differentiation and prognostic
bioprocesses. The novel coatings discovered in this study have significant
potential in providing both orthopedic and therapeutic functions.
Biotechnol. Bioeng. 2011;108: 454–464. © 2010 Wiley Periodicals,
Inc.},
doi = {10.1002/bit.22955},
issn = {1097-0290},
keywords = {bioactive glass, growth factors, osteoconduction, hydroxyapatite coating,
mRNA},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22955}
}
@ARTICLE{Tan2012,
author = {Fei Tan and Mariam Naciri and Denis Dowling and Mohamed Al-Rubeai},
title = {In vitro and in vivo bioactivity of CoBlast hydroxyapatite coating
and the effect of impaction on its osteoconductivity},
journal = {Biotechnology Advances},
year = {2012},
volume = {30},
pages = {352 - 362},
number = {1},
note = {Systems Biology for Biomedical Innovation},
abstract = {The novel non-thermal CoBlast process has been used recently to create
a hydroxyapatite coating on metallic substrates with improved biological
response compared to an uncoated implant. In this study, we compared
the biological effect of coatings deposited by this process and the
industrial standard technique — plasma-spray. Physicochemical properties
of these two coatings have been found to be significantly different
in that CoBlast HA is less rough but more hydrophilic than the plasma-spray
HA as evidenced by data obtained from profilometry and goniometry.
Mesenchymal stem cell attachment and adhesion are enhanced on CoBlast
HA. Analysis by a combination of EDX and ICP suggests that the higher
crystallinity retained by the CoBlast HA result in slower coating
dissolution. Detailed in vitro evaluation reveals that plasma-spray
HA might induce slightly faster cell proliferation and earlier osteogenic
differentiation, but CoBlast HA becomes equivalent to it by the late
osteogenic stage. PCR array facilitated the identification of differentially
regulated genes involved in various functional aspects of in vitro
osteogenesis by the CoBlast HA coating. The expression level of the
functional protein products of these genes are in agreement with
the PCR data. Coating metallic screws with HA significantly improves
the in vivo osseointegration. By measuring of removal force using
torque measurement instrument and analyzing the patterns found in
X-ray images it is demonstrated that the two HA coatings elicit comparable
osseointegration. Using simulated impaction model, CoBlast HA is
shown to maintain better performance in cell attachment and mineralization
than plasma-spray HA, especially following significant impactions.
This might indicate a potentially greater osteoconductivity of CoBlast
HA coating in shear-stress associated surgical applications. Collectively,
it was demonstrated that CoBlast HA is an effective alternative to
plasma-spray HA coating and a promising replacement for specialized
surgical applications.},
doi = {10.1016/j.biotechadv.2011.07.008},
issn = {0734-9750},
keywords = {Biomaterial},
url = {http://www.sciencedirect.com/science/article/pii/S0734975011001182}
}
@ARTICLE{Tan2011a,
author = {Fei Tan and Feidhlim O’Neill and Mariam Naciri and Denis Dowling
and Mohamed Al-Rubeai},
title = {Cellular and transcriptomic analysis of human mesenchymal stem cell
response to plasma-activated hydroxyapatite coating},
journal = {Acta Biomaterialia},
year = {2011},
pages = { - },
number = {0},
abstract = {Atmospheric pressure plasma has recently emerged as a technique with
a promising future in the medical field. In this work we used the
technique as a post-deposition modification process as a means to
activate hydroxyapatite (HA) coatings. Contact angle goniometry,
optical profilometry, scanning electron microscopy morphology imaging
and X-ray photoelectron spectroscopy analysis demonstrate that surface
wettability is improved after treatment, without inducing any concomitant
damage to the coating. The protein adsorption pattern has been found
to be preferable for MSC, and this may result in greater cell attachment
and adhesion to plasma-activated HA than to untreated samples. Cell
cycle distribution analysis using flow cytometry reveals a faster
transition from G1 to S phase, thus leading to a faster cell proliferation
rate on plasma-activated HA. This indicates that the improvement
in surface wettability independently enhances cell attachment and
cell proliferation, which is possibly mediated by FAK phosphorylation.
Pathway-specific polymerase chain reaction arrays revealed that wettability
has a substantial influence on gene expression during osteogenic
differentiation of human MSC. Plasma-activated HA tends to enhance
this process by systemically deregulating multiple genes. In addition,
the majority of these deregulated genes had been appropriately translated,
as confirmed by ELISA protein quantification. Lastly, alizarin red
staining showed that plasma-activated HA is capable of improving
mineralization for up to 3 weeks of in vitro culture. It was
concluded from this study that atmospheric pressure plasma is a potent
tool for modifying the biological function of a material without
causing thermal damage, such that adhesion molecules and drugs might
be deposited on the original coating to improve performance.},
doi = {10.1016/j.actbio.2011.12.014},
issn = {1742-7061},
keywords = {Plasma activation},
url = {http://www.sciencedirect.com/science/article/pii/S1742706111005502}
}
@ARTICLE{Tan2005,
author = {Tan, K.A.L. and Turner, K.J. and Saunders, P.T.K. and Verhoeven,
G. and De Gendt, K. and Atanassova, N. and Sharpe, R.M.},
title = {Androgen Regulation of Stage-Dependent Cyclin D2 Expression in Sertoli
Cells Suggests a Role in Modulating Androgen Action on Spermatogenesis},
journal = {Biol Reprod},
year = {2005},
volume = {72},
pages = {1151--1160},
number = {5},
month = may,
abstract = {Regulation of spermatogenesis involves stage-dependent androgen action
on Sertoli cells, but the pathways involved are unclear. We assessed
if cyclin D2 could play a role. In rats, Sertoli cell nuclear, stage-dependent
immunoexpression of cyclin D2 switched on after Day 10 and persisted
through Day 35, but disappeared by adulthood. However, ethane dimethane
sulfonate (EDS)-induced testosterone withdrawal in adult rats for
6 days induced stage-dependent cyclin D2 immunoexpression in Sertoli
cells, with highest expression at stages IX-XII and nondetectable
at stages VI-VIII (opposite that for androgen receptor [AR] immunoexpression).
In EDS-treated rats, a single injection of testosterone but not of
estrogen reversed this change in 4 h, and testosterone administration
from the time of EDS treatment prevented expression of cyclin D2
in Sertoli cells. The EDS-induced changes in cyclin D2 immunoexpression
were matched by changes in expression of Ccnd2 (cyclin D2) mRNA in
isolated stage-dissected tubules. Treatment of adult rats with flutamide
induced stage-dependent cyclin D2 immunoexpression in Sertoli cells
within 18 h, and confocal microscopy revealed that immunoexpression
of AR and cyclin D2 were mutually exclusive within individual seminiferous
tubules in these animals. Sertoli cell-selective ablation of the
AR in mice using Cre/loxP technology also resulted in stage-dependent
Sertoli cell cyclin D2 immunoexpression. Downstream from cyclin D2
action is retinoblastoma 1 (RB1), a tumor suppressor protein, immunoexpression
of which paralleled stage-dependent AR expression in Sertoli cells;
RB1 stage specificity disappeared after EDS treatment. These results
point to a non-cell cycle role for cyclin D2 and RB1 in mature Sertoli
cells in the stage-dependent mechanisms regulated by AR expression
and androgen action.},
url = {http://www.biolreprod.org/cgi/content/abstract/72/5/1151}
}
@ARTICLE{Tan2009a,
author = {Tan, Lu Ping and Seinen, Erwin and Duns, Gerben and de Jong, Debora
and Sibon, Ody C. M. and Poppema, Sibrand and Kroesen, Bart-Jan and
Kok, Klaas and van den Berg, Anke},
title = {A high throughput experimental approach to identify miRNA targets
in human cells},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {e137--},
number = {20},
month = nov,
abstract = {The study of human microRNAs is seriously hampered by the lack of
proper tools allowing genome-wide identification of miRNA targets.
We performed Ribonucleoprotein ImmunoPrecipitation--gene Chip (RIP-Chip)
using antibodies against wild-type human Ago2 in untreated Hodgkin
lymphoma (HL) cell lines. Ten to thirty percent of the gene transcripts
from the genome were enriched in the Ago2-IP fraction of untreated
cells, representing the HL miRNA-targetome. In silico analysis indicated
that [~]40% of these gene transcripts represent targets of the abundantly
co-expressed miRNAs. To identify targets of miR-17/20/93/106, RIP-Chip
with anti-miR-17/20/93/106 treated cells was performed and 1189 gene
transcripts were identified. These genes were analyzed for miR-17/20/93/106
target sites in the 5'-UTRs, coding regions and 3'-UTRs. Fifty-one
percent of them had miR-17/20/93/106 target sites in the 3'-UTR while
19% of them were predicted miR-17/20/93/106 targets by TargetScan.
Luciferase reporter assay confirmed targeting of miR-17/20/93/106
to the 3'-UTRs of 8 out of 10 genes. In conclusion, we report a method
which can establish the miRNA-targetome in untreated human cells
and identify miRNA specific targets in a high throughput manner.
This approach is applicable to identify miRNA targets in any human
tissue sample or purified cell population in an unbiased and physiologically
relevant manner.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/20/e137}
}
@ARTICLE{Tan2010,
author = {Tan, Michelle G. and Chua, Wei-Ting and Esiri, Margaret M. and Smith,
A. David and Vinters, Harry V. and Lai, Mitchell K.},
title = {Genome wide profiling of altered gene expression in the neocortex
of Alzheimer's disease},
journal = {J. Neurosci. Res.},
year = {2010},
volume = {88},
pages = {1157--1169},
number = {6},
abstract = {Abstract 10.1002/jnr.22290.abs Alzheimer's disease (AD) is characterized
by a complex neurodegenerative process affecting multiple genes and
proteins in the neocortex, many of which have not been well-studied.
In this study, we investigated genome-wide gene alterations in the
temporal cortex of a well-characterized cohort of AD patients using
a recently developed microarray platform, and compared some of the
transcript changes with immunoblotting. Of the 5485 genes found to
be significantly altered in AD, there were consistent patterns of
changes which show that the AD transcriptome in neocortex is characterized
by changes indicative of synaptic dysfunction, perturbed neurotransmission
and activation of neuroinflammation. We also highlighted several
genes of potential pathogenic significance which have not been well
studied in AD. The current study aims to add to the growing body
of knowledge relating to gene changes in AD and provide further insights
into pathogenic mechanisms and potential targets of pharmacotherapy.
© 2009 Wiley-Liss, Inc.},
issn = {1097-4547},
keywords = {Alzheimer's Disease, gene expression, microarray, neocortex, neuroinflammation,
neurotrans-mission, synapse},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.22290}
}
@ARTICLE{Tan2003,
author = {Tan, Paul K. and Downey, Thomas J. and Spitznagel, Edward L., Jr
and Xu, Pin and Fu, Dadin and Dimitrov, Dimiter S. and Lempicki,
Richard A. and Raaka, Bruce M. and Cam, Margaret C.},
title = {Evaluation of gene expression measurements from commercial microarray
platforms},
journal = {Nucleic Acids Res.},
year = {2003},
volume = {31},
pages = {5676--5684},
number = {19},
month = oct,
abstract = {Multiple commercial microarrays for measuring genome-wide gene expression
levels are currently available, including oligonucleotide and cDNA,
single- and two-channel formats. This study reports on the results
of gene expression measurements generated from identical RNA preparations
that were obtained using three commercially available microarray
platforms. RNA was collected from PANC-1 cells grown in serum-rich
medium and at 24 h following the removal of serum. Three biological
replicates were prepared for each condition, and three experimental
replicates were produced for the first biological replicate. RNA
was labeled and hybridized to microarrays from three major suppliers
according to manufacturers' protocols, and gene expression measurements
were obtained using each platform's standard software. For each platform,
gene targets from a subset of 2009 common genes were compared. Correlations
in gene expression levels and comparisons for significant gene expression
changes in this subset were calculated, and showed considerable divergence
across the different platforms, suggesting the need for establishing
industrial manufacturing standards, and further independent and thorough
validation of the technology.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/31/19/5676}
}
@ARTICLE{Tan2008a,
author = {Tan, Xiaojie and Zhai, Yujia and Chang, Wenjun and Hou, Jianguo and
He, Songqin and Lin, Liping and Yu, Yongwei and Xu, Danfeng and Xiao,
Jianru and Ma, Liye and Wang, Guoping and Cao, Tinghu and Cao, Guangwen},
title = {Global analysis of metastasis-associated gene expression in primary
cultures from clinical specimens of clear-cell renal-cell carcinoma},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {1080--1088},
number = {5},
abstract = {Abstract 10.1002/ijc.23637.abs Metastatic clear-cell renal-cell carcinoma
(ccRCC) has a poor prognosis and unpredictable course, and there
are no molecular markers that reliably predict ccRCC metastasis.
In this study, ccRCC specimens from 84 patients were directly cultured
in vitro. Primary cultures from 38 of 94 specimens contained more
than 90% tumor cells at the fourth passage. After identification
by immunostaining, the primary cultures of metastatic and nonmetastatic
ccRCC specimens from the age- and gender-matched patients were subjected
to cDNA microarray assays. A total of 842 differentially expressed
genes with a FDR (false discovery rate) of 4.79% were identified.
Pathway analysis and co-occurrence with “cancer�, “metastasis�
and “invasion� in the literature annotations functionally enriched
the 842 genes and provided an indication of the reliability of our
microarray assays. Novel genes associated with metastasis were selected
based on protein-protein interactions between 205 differentially
expressed genes that co-occurred with “metastasis� and those
that did not co-occur with “metastasis� on Medline, and the results
of co-expression analysis between the co-occurred genes and unpublished
genes. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1 were found
to be potential ccRCC metastasis-associated novel genes, according
to expression patterns in cultures and tumor tissues. Interestingly,
the upregulated genes (CAV1, PKMYT1 and ORC2L) were also upregulated
and the downregulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783)
were also downregulated in the primary ccRCC specimens compared with
expression in adjacent renal tissues in 37 patients. This study has
identified new candidate biomarkers and targets for the early diagnosis
and treatment of ccRCC metastasis. © 2008 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {renal-cell carcinoma, clear cell, metastasis, primary culture, gene
expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23637}
}
@ARTICLE{Tanackovic2011,
author = {Tanackovic, Goranka and Ransijn, Adriana and Thibault, Philippe and
Abou Elela, Sherif and Klinck, Roscoe and Berson, Eliot L. and Chabot,
Benoit and Rivolta, Carlo},
title = {PRPF mutations are associated with generalized defects in spliceosome
formation and pre-mRNA splicing in patients with retinitis pigmentosa},
journal = {Hum. Mol. Genet.},
year = {2011},
volume = {20},
pages = {2116--2130},
number = {11},
month = jun,
abstract = {Proteins PRPF31, PRPF3 and PRPF8 (RP-PRPFs) are ubiquitously expressed
components of the spliceosome, a macromolecular complex that processes
nearly all pre-mRNAs. Although these spliceosomal proteins are conserved
in eukaryotes and are essential for survival, heterozygous mutations
in human RP-PRPF genes lead to retinitis pigmentosa, a hereditary
disease restricted to the eye. Using cells from patients with 10
different mutations, we show that all clinically relevant RP-PRPF
defects affect the stoichiometry of spliceosomal small nuclear RNAs
(snRNAs), the protein composition of tri-small nuclear ribonucleoproteins
and the kinetics of spliceosome assembly. These mutations cause inefficient
splicing in vitro and affect constitutive splicing ex-vivo by impairing
the removal of at least 9% of endogenously expressed introns. Alternative
splicing choices are also affected when RP-PRPF defects are present.
Furthermore, we show that the steady-state levels of snRNAs and processed
pre-mRNAs are highest in the retina, indicating a particularly elevated
splicing activity. Our results suggest a role for PRPFs defects in
the etiology of PRPF-linked retinitis pigmentosa, which appears to
be a truly systemic splicing disease. Although these mutations cause
widespread and important splicing defects, they are likely tolerated
by the majority of human tissues but are critical for retinal cell
survival.},
comment = {10.1093/hmg/ddr094},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/20/11/2116}
}
@ARTICLE{Tanaka2010,
author = {Tanaka, Karo and Terryn, Sara and Geffers, Lars and Garbay, Serge
and Pontoglio, Marco and Devuyst, Olivier},
title = {The transcription factor HNF1{alpha} regulates expression of chloride-proton
exchanger ClC-5 in the renal proximal tubule},
journal = {Am J Physiol Renal Physiol},
year = {2010},
volume = {299},
pages = {F1339--1347},
number = {6},
month = dec,
abstract = {The Cl-/H+ exchanger ClC-5 is essential for the endocytic activity
of the proximal tubule cells and the tubular clearance of proteins
filtered in the glomeruli. The mechanisms that regulate the expression
of ClC-5 in general and its specific expression in the proximal tubule
are unknown. In this study, we investigated the hypothesis that the
hepatocyte nuclear transcription factor HNF1{alpha}, which is predominantly
expressed in proximal tubule segments, may directly regulate the
expression of ClC-5. In situ hybridization demonstrated that the
expression of Clcn5 overlaps with that of Hnf1{alpha} in the developing
kidney as well as in absorptive epithelia, including the digestive
tract and yolk sac. Multiple binding sites for HNF1 were mapped in
the 5'-regulatory sequences of the mouse and human Clcn5/CLCN5 genes.
The transactivation of the Clcn5/CLCN5 promoter by HNF1{alpha} was
verified in vitro, and the binding of HNF1{alpha} to the Clcn5 promoter
in vivo was confirmed by chromatin immunoprecipitation in mouse kidney.
The expression of Clcn5 was reduced in the proximal tubule segments
of HNF1{alpha}-null kidneys, and it was rescued upon transfection
of HNF1{alpha}-null cells with wild-type but not with mutant HNF1{alpha}.
These data demonstrate that HNF1{alpha} directly regulates the expression
of ClC-5 in the renal proximal tubule and yield insights into the
mechanisms governing epithelial differentiation and specialized transport
activities in the kidney.},
comment = {10.1152/ajprenal.00077.2010},
url = {http://ajprenal.physiology.org/cgi/content/abstract/299/6/F1339}
}
@ARTICLE{Tanaka2009,
author = {Tanaka, Kathleen Kelly and Hall, John K. and Troy, Andrew A. and
Cornelison, D.D.W. and Majka, Susan M. and Olwin, Bradley B.},
title = {Syndecan-4-Expressing Muscle Progenitor Cells in the SP Engraft as
Satellite Cells during Muscle Regeneration},
journal = {Cell Stem Cell},
year = {2009},
volume = {4},
pages = {217--225},
number = {3},
month = mar,
abstract = {Summary Skeletal muscle satellite cells, located between the basal
lamina and plasma membrane of myofibers, are required for skeletal
muscle regeneration. The capacity of satellite cells as well as other
cell lineages including mesoangioblasts, mesenchymal stem cells,
and side population (SP) cells to contribute to muscle regeneration
has complicated the identification of a satellite stem cell. We have
characterized a rare subset of the muscle SP that efficiently engrafts
into the host satellite cell niche when transplanted into regenerating
muscle, providing 75% of the satellite cell population and 30% of
the myonuclear population, respectively. These cells are found in
the satellite cell position, adhere to isolated myofibers, and spontaneously
undergo myogenesis in culture. We propose that this subset of SP
cells (satellite-SP cells), characterized by ABCG2, Syndecan-4, and
Pax7 expression, constitutes a self-renewing muscle stem cell capable
of generating both satellite cells and their myonuclear progeny in vivo.},
issn = {1934-5909},
keywords = {STEMCELL},
url = {http://www.sciencedirect.com/science/article/B8G3V-4VS4BH0-F/2/18095a174e03c63bfda97dde5ba7497a}
}
@ARTICLE{Tanaka2008,
author = {Tanaka, S. and Arii, S. and Yasen, M. and Mogushi, K. and Su, N.
T. and Zhao, C. and Imoto, I. and Eishi, Y. and Inazawa, J. and Miki,
Y. and Tanaka, H.},
title = {Aurora kinase B is a predictive factor for the aggressive recurrence
of hepatocellular carcinoma after curative hepatectomy},
journal = {Br J Surg},
year = {2008},
volume = {95},
pages = {611--619},
number = {5},
abstract = {Abstract 10.1002/bjs.6011.abs Background: Patterns of cancer recurrence
hold the key to prognosis after curative resection. This retrospective
study aimed to identify a predictor and therapeutic candidate for
aggressive recurrence of hepatocellular carcinoma (HCC). Methods:
Primary HCC tissues from 107 patients who had curative resection
were analysed. Genome-wide gene expression profiles were investigated
using a microarray technique, and clustering analysis was carried
out based on the first diagnosis of recurrence according to the Milan
criteria. Immunohistochemical expression and array-based comparative
genomic hybridization (array-CGH) were also assessed. Results: Microarray
analysis revealed overexpression of Aurora kinase B, a chromosome
passenger protein kinase, as the most significant predictor of the
aggressive recurrence of HCC. Aurora kinase B protein expression
was significantly associated with aggressive recurrence (P < 0·001)
and prognosis (P < 0·001). Multivariable analysis identified Aurora
kinase B as the only independent predictor of aggressive recurrence
of HCC (P = 0·031). Array-CGH analysis showed that genomic instability
was closely related to Aurora kinase B expression (P = 0·011). Conclusion:
Aurora kinase B is an effective predictor of aggressive HCC recurrence,
in relation to the genomic instability. It might be worth considering
as a molecular target for the adjuvant therapy of HCC. Copyright
© 2008 British Journal of Surgery Society Ltd. Published by John
Wiley & Sons, Ltd.},
issn = {1365-2168},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/bjs.6011}
}
@ARTICLE{Tanaka2011,
author = {Tanaka, Shinji and Mogushi, Kaoru and Yasen, Mahmut and Ban, Daisuke
and Noguchi, Norio and Irie, Takumi and Kudo, Atsushi and Nakamura,
Noriaki and Tanaka, Hiroshi and Yamamoto, Masakazu and Kokudo, Norihiro
and Takayama, Tadatoshi and Kawasaki, Seiji and Sakamoto, Michiie
and Arii, Shigeki},
title = {Oxidative stress pathways in noncancerous human liver tissue to predict
hepatocellular carcinoma recurrence: A prospective, multicenter study},
journal = {Hepatology},
year = {2011},
volume = {54},
pages = {1273--1281},
number = {4},
abstract = {The prediction of cancer recurrence holds the key to improvement of
the postoperative prognosis of patients. In this study, the recurrence
of early-stage hepatocellular carcinoma (HCC) after curative hepatectomy
was analyzed by the genome-wide gene-expression profiling on cancer
tissue and the noncancerous liver tissue. Using the training set
of 78 cases, the cytochrome P450 1A2 (CYP1A2) gene in noncancerous
liver tissue was identified as the predictive candidate for postoperative
recurrence (hazard ratio [HR], 0.447; 95% confidence interval [CI],
0.249-0.808; P = 0.010). Multivariate analysis revealed the statistically
significant advantage of CYP1A2 down-regulation to predict recurrence
(odds ratio, 0.534; 95% CI, 0.276-0.916; P = 0.036), and the expression
of CYP1A2 protein was confirmed immunohistochemically. An independently
multi-institutional cohort of 211 patients, using tissue microarrays,
validated that loss of expression of CYP1A2 in noncancerous liver
tissue as the only predictive factor of recurrence after curative
hepatectomy for early-stage HCC (HR, 0.480; 95% CI, 0.256-0.902;
P = 0.038). Gene set-enrichment analysis revealed close association
of CYP1A2 down-regulation with oxidative stress pathways in liver
tissue (P < 0.001, false discovery rate [FDR] = 0.042; P = 0.006,
FDR = 0.035). Our results indicate these pathways as the molecular
targets to prevent recurrence, as well as the potential prediction
of the super high-risk population of HCC using liver tissue. (HEPATOLOGY
2011;54:1273–1281)},
doi = {10.1002/hep.24536},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.24536}
}
@ARTICLE{Tanaka2009a,
author = {Tanaka, Shinji and Mogushi, Kaoru and Yasen, Mahmut and Noguchi,
Norio and Kudo, Atsushi and Kurokawa, Toshiaki and Nakamura, Noriaki
and Inazawa, Johji and Tanaka, Hiroshi and Arii, Shigeki},
title = {Surgical Contribution to Recurrence-Free Survival in Patients with
Macrovascular-Invasion-Negative Hepatocellular Carcinoma},
journal = {Journal of the American College of Surgeons},
year = {2009},
volume = {208},
pages = {368--374.e128},
number = {3},
month = mar,
abstract = {Background Macroscopic vascular invasion (MVI) is a well-known indicator
of recurrence of hepatocellular carcinoma (HCC) even after curative
hepatectomy, but the clinicopathologic and molecular features of
the recurrence remain unclear in MVI-negative HCC.Study Design Two
hundred seven consecutive patients with confirmed primary MVI-negative
HCC were retrospectively assessed after curative resection, with
special emphasis on the importance of anatomically systematized hepatectomy.
HCC tissues were also analyzed for genome-wide gene expression profile
of each tumor using a microarray technique.Results Univariant analysis
of HCC recurrence revealed multiple tumors (p < 0.001), moderate
to poor differentiation (p = 0.044), Child-Pugh B/C (p = 0.047),
[alpha]-fetoprotein elevation (p = 0.007), and nonanatomic hepatectomy
(p = 0.010) as risk factors. According to Cox hazard multivariant
analysis, multiple tumors (p = 0.002), [alpha]-fetoprotein elevation
(p < 0.001), and nonanatomic hepatectomy (p = 0.002) were identified
as independent factors of the recurrence. In the recurrent cases
after anatomic hepatectomy for HCC, local recurrence was significantly
infrequent compared with those after nonanatomic hepatectomy (p <
0.001). Network expression analysis using cDNA microarray revealed
distinct signaling pathways of epithelial-mesenchymal transitions
are associated with recurrence after anatomically systematized hepatectomy.Conclusions
Anatomically systematized hepatectomy might contribute to recurrence-free
survival of HCC patients of HCC without MVI. Local recurrence could
be mostly averted by anatomic hepatectomy, although specific epithelial-mesenchymal
transitions signaling might regulate the biologic aggressiveness
of HCC.},
issn = {1072-7515},
url = {http://www.sciencedirect.com/science/article/B6T91-4VNGRRX-4/2/ae7fed376f0288bd9550f546eb0930de}
}
@ARTICLE{Tanaka2010a,
author = {Tanaka, Shinji and Mogushi, Kaoru and Yasen, Mahmut and Noguchi,
Norio and Kudo, Atsushi and Nakamura, Noriaki and Ito, Koji and Miki,
Yoshio and Inazawa, Johji and Tanaka, Hiroshi and Arii, Shigeki},
title = {Gene-expression phenotypes for vascular invasiveness of hepatocellular
carcinomas},
journal = {Surgery},
year = {2010},
volume = {147},
pages = {405--414},
number = {3},
month = mar,
abstract = {Background Gross vascular invasion is a well-established prognostic
indicator in hepatocellular carcinoma (HCC), but the biological significance
of microscopic invasion remains unclear.Methods Curatively resected
primary HCCs were classified retrospectively into 3 groups: HCCs
without vascular invasion (V0), HCCs with microvascular invasion
(V1), and HCCs with macrovascular invasion (V2). Microarray profiling
of patients with V0, V1, and V2 using Jonckheere-Terpstra (JT) tests
and Wilcoxon rank sum tests was performed.Results Distinct patterns
of gene expression were demonstrated between V0 and V2 groups; less
(L) and highly (H) invasive phenotypes, respectively. It is noteworthy
that 2 dendrograms by the hierarchical clustering provided exactly
the same assignment results for V1 cases that were thus separated
into L and H gene-expression phenotypes. Marked differences were
found in overall (P < .001) and tumor-free survival (P < .001) between
L and H gene-expression phenotypes. Multivariate analyses indicated
that the phenotypes of the patterns of gene expression, rather than
the clinicopathologic markers of vascular invasion, were independent
predictors of tumor recurrence (P = .031). Using the gene-expression
patterns identified by both JT and Wilcoxon rank sum test analyses,
other V1 cases validated these differences in tumor-free survivals
between gene-expression phenotypes within the group (P = .039).Conclusion
Gene profiling suggested that microvascular invasiveness consisted
of a classable mixture of 2 distinct phenotypes. Thus, gene-array
analyses may have clinical benefit, because they may in fact be more
predictive than other clinical factors.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4XT2CJJ-1/2/11ebe55df5c46bce16d548a09d59f3ed}
}
@ARTICLE{Tanaka2002,
author = {Tanaka, Tetsuya S. and Kunath, Tilo and Kimber, Wendy L. and Jaradat,
Saied A. and Stagg, Carole A. and Usuda, Masayuki and Yokota, Takashi
and Niwa, Hitoshi and Rossant, Janet and Ko, Minoru S.H.},
title = {Gene Expression Profiling of Embryo-Derived Stem Cells Reveals Candidate
Genes Associated With Pluripotency and Lineage Specificity},
journal = {Genome Res.},
year = {2002},
volume = {12},
pages = {1921--1928},
number = {12},
month = dec,
abstract = {Large-scale gene expression profiling was performed on embryo-derived
stem cell lines to identify molecular signatures of pluripotency
and lineage specificity. Analysis of pluripotent embryonic stem (ES)
cells, extraembryonic-restricted trophoblast stem (TS) cells, and
terminally-differentiated mouse embryo fibroblast (MEF) cells identified
expression profiles unique to each cell type, as well as genes common
only to ES and TS cells. Whereas most of the MEF-specific genes had
been characterized previously, the majority (67%) of the ES-specific
genes were novel and did not include known differentiated cell markers.
Comparison with microarray data from embryonic material demonstrated
that ES-specific genes were underrepresented in all stages sampled,
whereas TS-specific genes included known placental markers. Investigation
of four novel TS-specific genes showed trophoblast-restricted expression
in cell lines and in vivo, whereas one uncharacterized ES-specific
gene, Esg-1, was found to be exclusively associated with pluripotency.
We suggest that pluripotency requires a set of genes not expressed
in other cell types, whereas lineage-restricted stem cells, like
TS cells, express genes predictive of their differentiated lineage.[Supplemental
material is available online at www.genome.org and http://lgsun.grc.nia.nih.gov/microarray/data.html]},
url = {http://genome.cshlp.org/cgi/content/abstract/12/12/1921}
}
@ARTICLE{Tanaka-Tsuno2007,
author = {Tanaka-Tsuno, Fumiko and Mizukami-Murata, Satomi and Murata, Yoshinori
and Nakamura, Toshihide and Ando, Akira and Takagi, Hiroshi and Shima,
Jun},
title = {Functional genomics of commercial baker's yeasts that have different
abilities for sugar utilization and high-sucrose tolerance under
different sugar conditions},
journal = {Yeast},
year = {2007},
volume = {24},
pages = {901--911},
number = {10},
abstract = {Abstract 10.1002/yea.1541.abs In the modern baking industry, high-sucrose-tolerant
(HS) and maltose-utilizing (LS) yeast were developed using breeding
techniques and are now used commercially. Sugar utilization and high-sucrose
tolerance differ significantly between HS and LS yeasts. We analysed
the gene expression profiles of HS and LS yeasts under different
sucrose conditions in order to determine their basic physiology.
Two-way hierarchical clustering was performed to obtain the overall
patterns of gene expression. The clustering clearly showed that the
gene expression patterns of LS yeast differed from those of HS yeast.
Quality threshold clustering was used to identify the gene clusters
containing upregulated genes (cluster 1) and downregulated genes
(cluster 2) under high-sucrose conditions. Clusters 1 and 2 contained
numerous genes involved in carbon and nitrogen metabolism, respectively.
The expression level of the genes involved in the metabolism of glycerol
and trehalose, which are known to be osmoprotectants, in LS yeast
was higher than that in HS yeast under sucrose concentrations of
5–40%. No clear correlation was found between the expression level
of the genes involved in the biosynthesis of the osmoprotectants
and the intracellular contents of the osmoprotectants. The present
gene expression data were compared with data previously reported
in a comprehensive analysis of a gene deletion strain collection.
Welch's t-test for this comparison showed that the relative growth
rates of the deletion strains whose deletion occurred in genes belonging
to cluster 1 were significantly higher than the average growth rates
of all deletion strains. Copyright © 2007 John Wiley & Sons, Ltd.},
issn = {1097-0061},
keywords = {baker's yeast, gene expression, high-sucrose stress, DNA microarray,
bread baking},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/yea.1541}
}
@ARTICLE{Tanas2011,
author = {Tanas, Munir R. and Sboner, Andrea and Oliveira, Andre M. and Erickson-Johnson,
Michele R. and Hespelt, Jessica and Hanwright, Philip J. and Flanagan,
John and Luo, Yuling and Fenwick, Kerry and Natrajan, Rachael and
Mitsopoulos, Costas and Zvelebil, Marketa and Hoch, Benjamin L. and
Weiss, Sharon W. and Debiec-Rychter, Maria and Sciot, Raf and West,
Rob B. and Lazar, Alexander J. and Ashworth, Alan and Reis-Filho,
Jorge S. and Lord, Christopher J. and Gerstein, Mark B. and Rubin,
Mark A. and Rubin, Brian P.},
title = {Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma},
journal = {Science Translational Medicine},
year = {2011},
volume = {3},
pages = {98ra82},
number = {98},
abstract = {Integrating transcriptomic sequencing with conventional cytogenetics,
we identified WWTR1 (WW domain-containing transcription regulator
1) (3q25) and CAMTA1 (calmodulin-binding transcription activator
1) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal
translocation that is characteristic of epithelioid hemangioendothelioma
(EHE), a vascular sarcoma. This WWTR1/CAMTA1 gene fusion is under
the transcriptional control of the WWTR1 promoter and encodes a putative
chimeric transcription factor that joins the amino terminus of WWTR1,
a protein that is highly expressed in endothelial cells, in-frame
to the carboxyl terminus of CAMTA1, a protein that is normally expressed
only in brain. Thus, CAMTA1 expression is activated inappropriately
through a promoter-switch mechanism. The gene fusion is present in
virtually all EHEs tested but is absent from all other vascular neoplasms,
demonstrating it to be a disease-defining genetic alteration. A sensitive
and specific break-apart fluorescence in situ hybridization assay
was also developed to detect the translocation and will assist in
the evaluation of this diagnostically challenging neoplasm. The chimeric
WWTR1/CAMTA1 transcription factor may represent a therapeutic target
for EHE and offers the opportunity to shed light on the functions
of two poorly characterized proteins.},
doi = {10.1126/scitranslmed.3002409},
eprint = {http://stm.sciencemag.org/cgi/reprint/3/98/98ra82.pdf},
url = {http://stm.sciencemag.org/cgi/content/abstract/3/98/98ra82}
}
@ARTICLE{Taneda2008,
author = {Taneda, Sekiko and Hudkins, Kelly L. and Muhlfeld, Anja S. and Kowalewska,
Jolanta and Pippin, Jeffrey W. and Shankland, Stuart J. and Alpers,
Charles E.},
title = {Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic
Membranoproliferative Glomerulonephritis},
journal = {J. Am. Soc. Nephrol.},
year = {2008},
volume = {19},
pages = {243--251},
number = {2},
month = feb,
url = {http://jasn.asnjournals.org}
}
@ARTICLE{Tanetani2009,
author = {Tanetani, Yoshitaka and Kaku, Koichiro and Kawai, Kiyoshi and Fujioka,
Tomonori and Shimizu, Tsutomu},
title = {Action mechanism of a novel herbicide, pyroxasulfone},
journal = {Pesticide Biochemistry and Physiology},
year = {2009},
volume = {95},
pages = {47--55},
number = {1},
month = sep,
abstract = {The mechanism of action of pyroxasulfone was studied by examination
of the inhibitory effects of this herbicide on the biosynthesis of
very-long-chain fatty acids (VLCFAs) both in vivo and in vitro. Pyroxasulfone
treatment drastically reduced the biosynthesis of VLCFAs and caused
a buildup of fatty acid precursors in cultured rice cells. Pyroxasulfone
specifically inhibited the elongation steps from C18:0 to C20:0,
C20:0 to C22:0, C22:0 to C24:0, C24:0 to C26:0 and C26:0 to C28:0,
catalyzed by VLCFA elongases (VLCFAEs) in plants including rice.
These results suggested that pyroxasulfone is a potent inhibitor
of VLCFA biosynthesis, and should be categorized within the K3 group
of herbicides. Twenty putative VLCFAEs of rice were identified by
blastp search with the amino acid sequences of Arabidopsis VLCFAEs.
Oligo microarray and real time RT-PCR analysis revealed that Q5Z6S3
and Q8H7Z0, which were identified by their Uniplot ID number, might
play important roles during the biosynthesis of C28:0 and C30:0 VLCFAs
in shoot formation, and biosynthesis of C20:1 and C22:1 VLCFAs in
cell proliferation, respectively. These VLCFAEs are likely targets
for pyroxasulfone.},
issn = {0048-3575},
keywords = {Pyroxasulfone, KIH-485, Very-long-chain fatty acid, VLCFA, Elongase,
VLCFAE, Uniplot ID number, Mode of action, MOA},
url = {http://www.sciencedirect.com/science/article/B6WP8-4WGMB3Y-4/2/7b907cf1f918a6f6f870511e6002e8f7}
}
@ARTICLE{Tang2009,
author = {Tang, Junxia and LeGros, Robert P. and Louneva, Natalia and Yeh,
Lilly and Cohen, Julia W. and Hahn, Chang-Gyu and Blake, Derek J.
and Arnold, Steven E. and Talbot, Konrad},
title = {Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases
is reduced in an isoform-specific manner unrelated to dysbindin-1
mRNA expression},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {3851--3863},
number = {20},
month = oct,
abstract = {DTNBP1 (dystrobrevin binding protein 1) remains a top candidate gene
in schizophrenia. Reduced expression of this gene and of its encoded
protein, dysbindin-1, have been reported in the brains of schizophrenia
cases. It has not been established, however, if the protein reductions
encompass all dysbindin-1 isoforms or if they are associated with
decreased DTNBP1 gene expression. Using a matched pairs design in
which each of 28 Caucasian schizophrenia cases was matched in age
and sex to a normal Caucasian control, Western blotting of whole-tissue
lysates of dorsolateral prefrontal cortex (DLPFC) revealed significant
reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia
(P = 0.022). These reductions occurred without any significant change
in levels of the encoding transcript in the same tissue samples and
in the absence of the only DTNBP1 risk haplotype for schizophrenia
reported in the USA. Indeed, no significant correlations were found
between case-control differences in any dysbindin-1 isoform and the
case-control differences in its encoding mRNA. Consequently, the
mean 60% decrease in dysbindin-1C observed in 71% of our case-control
pairs appears to reflect abnormalities in mRNA translation and/or
processes promoting dysbindin-1C degradation (e.g. oxidative stress,
phosphorylation and/or ubiquitination). Given the predominantly post-synaptic
localization of dysbindin-1C and known post-synaptic effects of dysbindin-1
reductions in the rodent equivalent of the DLPFC, the present findings
suggest that decreased dysbindin-1C in the DLPFC may contribute to
the cognitive deficits of schizophrenia by promoting NMDA receptor
hypofunction in fast-spiking interneurons.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/20/3851}
}
@ARTICLE{Tang2011,
author = {Tang, Jianwei and Ohyama, Kiyoshi and Kawaura, Kanako and Hashinokuchi,
Hiromi and Kamiya, Yoko and Suzuki, Masashi and Muranaka, Toshiya
and Ogihara, Yasunari},
title = {A New Insight into Application for Barley Chromosome Addition Lines
of Common Wheat: Achievement of Stigmasterol Accumulation},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {1555-1567},
number = {3},
abstract = {Barley (Hordeum vulgare) has a much higher content of bioactive substances
than wheat (Triticum aestivum). In order to investigate additive
and/or synergistic effect(s) on the phytosterol content of barley
chromosomes, we used a series of barley chromosome addition lines
of common wheat that were produced by normal crossing. In determining
the plant sterol levels in 2-week-old seedlings and dry seeds, we
found that the level of stigmasterol in the barley chromosome 3 addition
(3H) line in the seedlings was 1.5-fold higher than that in the original
wheat line and in the other barley chromosome addition lines, but
not in the seeds. Simultaneously, we determined the overall expression
pattern of genes related to plant sterol biosynthesis in the seedlings
of wheat and each addition line to assess the relative expression
of each gene in the sterol pathway. Since we elucidated the CYP710A8
(cytochrome P450 subfamily)-encoding sterol C-22 desaturase as a
key characteristic for the higher level of stigmasterol, full-length
cDNAs of wheat and barley CYP710A8 genes were isolated. These CYP710A8
genes were mapped on chromosome 3 in barley (3H) and wheat (3A, 3B,
and 3D), and the expression of CYP710A8 genes increased in the 3H
addition line, indicating that it is responsible for stigmasterol
accumulation. Overexpression of the CYP710A8 genes in Arabidopsis
increased the stigmasterol content but did not alter the total sterol
level. Our results provide new insight into the accumulation of bioactive
compounds in common wheat and a new approach for assessing plant
metabolism profiles.},
doi = {10.1104/pp.111.183533},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/3/1555.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/3/1555}
}
@ARTICLE{TANG2007,
author = {TANG, Rongying and DODD, Andrew and LAI, Daniel and MCNABB, Warren
C. and LOVE, Donald R.},
title = {Validation of Zebrafish (Danio rerio) Reference Genes for Quantitative
Real-time RT-PCR Normalization},
journal = {Acta Biochimica et Biophysica Sinica},
year = {2007},
volume = {39},
pages = {384--390},
number = {5},
abstract = {Abstract The normalization of quantitative real time RT-PCR (qRT-PCR)
is important to obtain accurate gene expression data. The most common
method for qRT-PCR normalization is to use reference, or house keeping
genes. However, there is emerging evidence that even reference genes
can be regulated under different conditions. qRT-PCR has only recently
been used in terms of zebrafish gene expression studies and there
is no validated set of reference genes. This study characterizes
the expression of nine possible reference genes during zebrafish
embryonic development and in a zebrafish tissue panel. All nine reference
genes exhibited variable expression. The β-actin, EF1α and Rpl13α
genes comprise a validated reference gene panel for zebrafish developmental
time course studies, and the EF1α, Rpl13α and 18S rRNA genes are
more suitable as a reference gene panel for zebrafish tissue analysis.
Importantly, the zebrafish GAPDH gene appears unsuitable as reference
gene for both types of studies.},
issn = {1745-7270},
keywords = {zebrafish, quantitative real-time RT-PCR, housekeeping genes, GAPDH
gene, GeNorm},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1745-7270.2007.00283.x}
}
@ARTICLE{Tang2007,
author = {Tang, Sung-Chun and Arumugam, Thiruma V. and Xu, Xiangru and Cheng,
Aiwu and Mughal, Mohamed R. and Jo, Dong Gyu and Lathia, Justin D.
and Siler, Dominic A. and Chigurupati, Srinivasulu and Ouyang, Xin
and Magnus, Tim and Camandola, Simonetta and Mattson, Mark P.},
title = {Pivotal role for neuronal Toll-like receptors in ischemic brain injury
and functional deficits},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {13798--13803},
number = {34},
month = aug,
abstract = {The innate immune system senses the invasion of pathogenic microorganisms
and tissue injury through Toll-like receptors (TLR), a mechanism
thought to be limited to immune cells. We now report that neurons
express several TLRs, and that the levels of TLR2 and -4 are increased
in neurons in response to IFN-{gamma} stimulation and energy deprivation.
Neurons from both TLR2 knockout and -4 mutant mice were protected
against energy deprivation-induced cell death, which was associated
with decreased activation of a proapoptotic signaling cascade involving
jun N-terminal kinase and the transcription factor AP-1. TLR2 and
-4 expression was increased in cerebral cortical neurons in response
to ischemia/reperfusion injury, and the amount of brain damage and
neurological deficits caused by a stroke were significantly less
in mice deficient in TLR2 or -4 compared with WT control mice. Our
findings establish a proapoptotic signaling pathway for TLR2 and
-4 in neurons that may render them vulnerable to ischemic death.},
url = {http://www.pnas.org/cgi/content/abstract/104/34/13798}
}
@ARTICLE{Tang2009a,
author = {Tang, Weining and David, Freedom B. and Wilson, Malania M. and Barwick,
Benjamin G. and Leyland-Jones, Brian R. and Bouzyk, Mark M.},
title = {DNA Extraction from Formalin-Fixed, Paraffin-Embedded Tissue},
journal = {Cold Spring Harb Protoc},
year = {2009},
volume = {2009},
pages = {pdb.prot5138--},
number = {2},
month = feb,
abstract = {IntroductionFormalin-fixed, paraffin-embedded (FFPE) tissue is one
of the most widely practiced methods for clinical sample preservation
and archiving. It is estimated that, worldwide, over a billion tissue
samples, most of them FFPE, are being stored in numerous hospitals,
tissue banks, and research laboratories. These archived samples could
potentially provide a wealth of information in retrospective molecular
studies of diseased tissues. While standard for histopathology and
microscopic investigation (e.g., hematoxylin and eosin [H&E] staining,
immunohistochemistry [IHC], and tissue microarray [TMA]), FFPE samples
pose a major challenge for molecular pathologists, because nucleic
acids are heavily modified and trapped by extensive protein-nucleic
acid and protein-protein cross linking. Historically, FFPE samples
were not considered to be a viable source for molecular analyses.
Recently, however, it has been discovered that with appropriate protease
digestion, it is possible to release microgram amounts of DNA and
RNA from FFPE samples. The purified nucleic acids, although highly
fragmented, are suitable for a variety of downstream genomic and
gene expression analyses, such as polymerase chain reaction (PCR),
quantitative reverse transcription PCR (qRT-PCR), microarray, array
comparative genomic hybridization (CGH), microRNA, and methylation
profiling. Several commercial kits are currently available for FFPE
extraction. The protocol reported here is adapted from the Ambion
RecoverAll Total Nucleic Acid Isolation Kit, but includes several
modifications. Although our protocol focuses on DNA isolation, the
RecoverAll Kit can also be utilized to recover RNA, including microRNA.},
url = {http://cshprotocols.cshlp.org/cgi/content/abstract/2009/2/pdb.prot5138}
}
@ARTICLE{Tang2012,
author = {Weihua Tang and Zhiyuan Hu and Hind Muallem and Margaret L. Gulley},
title = {Quality Assurance of RNA Expression Profiling in Clinical Laboratories},
journal = {The Journal of Molecular Diagnostics},
year = {2012},
volume = {14},
pages = {1 - 11},
number = {1},
abstract = {RNA expression profiles are increasingly used to diagnose and classify
disease, based on expression patterns of as many as several thousand
RNAs. To ensure quality of expression profiling services in clinical
settings, a standard operating procedure incorporates multiple quality
indicators and controls, beginning with preanalytic specimen preparation
and proceeding thorough analysis, interpretation, and reporting.
Before testing, histopathological examination of each cellular specimen,
along with optional cell enrichment procedures, ensures adequacy
of the input tissue. Other tactics include endogenous controls to
evaluate adequacy of RNA and exogenous or spiked controls to evaluate
run- and patient-specific performance of the test system, respectively.
Unique aspects of quality assurance for array-based tests include
controls for the pertinent outcome signatures that often supersede
controls for each individual analyte, built-in redundancy for critical
analytes or biochemical pathways, and software-supported scrutiny
of abundant data by a laboratory physician who interprets the findings
in a manner facilitating appropriate medical intervention. Access
to high-quality reagents, instruments, and software from commercial
sources promotes standardization and adoption in clinical settings,
once an assay is vetted in validation studies as being analytically
sound and clinically useful. Careful attention to the well-honed
principles of laboratory medicine, along with guidance from government
and professional groups on strategies to preserve RNA and manage
large data sets, promotes clinical-grade assay performance.},
doi = {10.1016/j.jmoldx.2011.09.003},
issn = {1525-1578},
url = {http://www.sciencedirect.com/science/article/pii/S1525157811002637}
}
@ARTICLE{Tang2007a,
author = {Tang, Xiaoqing and Gal, Jozsef and Zhuang, Xun and Wang, Wangxia
and Zhu, Haining and Tang, Guiliang},
title = {A simple array platform for microRNA analysis and its application
in mouse tissues},
journal = {RNA},
year = {2007},
volume = {13},
pages = {1803--1822},
number = {10},
month = oct,
abstract = {MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that
regulate gene expression at the post-transcriptional level and play
a critical role in many important biological processes. Most miRNAs
are conserved between humans and mice, which makes it possible to
analyze their expressions with a set of selected array probes. Here,
we report a simple array platform that can detect 553 nonredundant
miRNAs encompassing the entire set of miRNAs for humans and mice.
The platform features carefully selected and designed probes with
optimized hybridization parameters. Potential cross-reaction between
mature miRNAs and their precursors was investigated. The array platform
was used to analyze miRNAs in the mouse central nervous system (CNS,
spinal cord and brain), and two other non-CNS organs (liver and heart).
Two types of miRNAs, differentially expressed organ/tissue-associated
miRNAs and ubiquitously expressed miRNAs, were detected in the array
analysis. In addition to the previously reported neuron-related miR-124a,
liver-related miR-122a, and muscle-related miR-133a, we also detected
new tissue-associated miRNAs (e.g., liver-associated miR-194). Interestingly,
while the majority of pre-miRNAs were undetectable, miR690, miR709,
and miR720 were clearly detected at both mature and precursor levels
by the array analysis, indicating a limited cross-reaction between
pre-miRNAs and their mature miRNAs. The reliability of this array
technology was validated by comparing the results with independent
Northern blot analyses and published data. A new approach of data
normalization based on Northern blot analysis of one ubiquitously
expressed miRNA is introduced and compared with traditional approaches.
We expect this miRNA array platform to be useful for a wide variety
of biological studies.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/13/10/1803}
}
@ARTICLE{Tang2010,
author = {Tang, Xiang and Zhang, Zhi-Yong and Zhang, Wen-Juan and Zhao, Xing-Ming
and Li, Xuan and Zhang, Dong and Liu, Qiao-Quan and Tang, Wei-Hua},
title = {Global Gene Profiling of Laser-Captured Pollen Mother Cells Indicates
Molecular Pathways and Gene Subfamilies Involved in Rice Meiosis},
journal = {Plant Physiology},
year = {2010},
volume = {154},
pages = {1855--1870},
number = {4},
month = dec,
abstract = {Pollen mother cells (PMCs) represent a critical early stage in plant
sexual reproduction in which the stage is set for male gamete formation.
Understanding the global molecular genetics of this early meiotic
stage has so far been limited to whole stamen or floret transcriptome
studies, but since PMCs are a discrete population of cells in developmental
synchrony, they provide the potential for precise transcriptome analysis
and for enhancing our understanding of the transition to meiosis.
As a step toward identifying the premeiotic transcriptome, we performed
microarray analysis on a homogenous population of rice (Oryza sativa)
PMCs isolated by laser microdissection and compared them with those
of tricellular pollen and seedling. Known meiotic genes, including
OsSPO11-1, PAIR1, PAIR2, PAIR3, OsDMC1, OsMEL1, OsRAD21-4, OsSDS,
and ZEP1, all showed preferential expression in PMCs. The Kyoto Encyclopedia
of Genes and Genomes pathways significantly enriched in PMC-preferential
genes are DNA replication and repair pathways. Our genome-wide survey
showed that, in the buildup to meiosis, PMCs accumulate the molecular
machinery for meiosis at the mRNA level. We identified 1,158 PMC-preferential
genes and suggested candidate genes and pathways involved in meiotic
recombination and meiotic cell cycle control. Regarding the developmental
context for meiosis, the DEF-like, AGL2-like, and AGL6-like subclades
of MADS box transcription factors are PMC-preferentially expressed,
the trans-zeatin type of cytokinin might be preferentially synthesized,
and the gibberellin signaling pathway is likely active in PMCs. The
ubiquitin-mediated proteolysis pathway is enriched in the 127 genes
that are expressed in PMCs but not in tricellular pollen or seedling.},
comment = {10.1104/pp.110.161661},
url = {http://www.plantphysiol.org/cgi/content/abstract/154/4/1855}
}
@ARTICLE{Tang2005,
author = {Tang, Yang and Gilbert, Donald L. and Glauser, Tracy A. and Hershey,
Andrew D. and Sharp, Frank R.},
title = {Blood Gene Expression Profiling of Neurologic Diseases: A Pilot Microarray
Study},
journal = {Arch Neurol},
year = {2005},
volume = {62},
pages = {210--215},
number = {2},
month = feb,
abstract = {Background Tissue gene expression profiling with arrays measures the
transcription of thousands of genes. However, this approach cannot
be readily used to guide clinical neurologic practice. Objectives
To determine whether clinical neurologic diseases are associated
with unique patterns of up- and down-regulated genes in whole blood
and to explore the possibility of using peripheral blood as a surrogate
tissue in these diseases. Design Case-control study. Setting University-based
pediatric and adult neurology clinics. Participants Patients with
neurofibromatosis type 1, epilepsy, or Tourette syndrome diagnosed
using traditional clinical criteria; controls without disease; and
controls with neurologic disease. Main Outcome Measure Blood gene
expression levels of greater than 12 000 genes, measured using U95A
arrays. Results Neurofibromatosis type 1 and childhood epilepsy treated
with carbamazepine or valproic acid are associated with distinct
patterns of blood gene expression. Patients with valproic acid-responsive
vs valproic acid-refractory epilepsy formed distinct subclusters.
Tourette syndrome was characterized by several gene expression clusters.
In 1 cluster, 6 genes--all associated with immune cell function--were
overexpressed. Conclusion Blood gene expression profiling can provide
surrogate markers for neurologic diseases without obvious blood phenotypes.},
url = {http://archneur.ama-assn.org/cgi/content/abstract/62/2/210}
}
@ARTICLE{Tang2004,
author = {Tang, Y. and Glauser, T. A. and Gilbert, D. L. and Hershey, A. D.
and Privitera, M. D. and Ficker, D. M. and Szaflarski, J. P. and
Sharp, F. R.},
title = {Valproic acid blood genomic expression patterns in children with
epilepsy – a pilot study},
journal = {Acta Neurologica Scandinavica},
year = {2004},
volume = {109},
pages = {159--168},
number = {3},
abstract = {Objective – Valproic acid (VPA) is a commonly used anticonvulsant
with multiple systemic effects. The purpose of this pilot study is
to examine the blood genomic expression pattern associated with VPA
therapy in general and secondly VPA efficacy in children with epilepsy.
Materials and methods – Using oligonucleotide microarrays, gene
expression in whole blood was assessed in pediatric epilepsy patients
following treatment with VPA compared with children with epilepsy
prior to initiation of anticonvulsant therapy (drug free patients).
Results – The expression of 461 genes was altered in VPA patients
(n = 11) compared with drug free patients (n = 7), among which
a significant number of serine threonine kinases were down-regulated.
Expression patterns in children seizure free on VPA therapy (n = 8)
demonstrated 434 up-regulated genes, many in mitochondria, compared
with VPA children with continuing seizures (n = 3) and drug free
seizure patients (n = 7). Conclusion – VPA therapy is associated
with two significant and unique blood gene expression patterns: chronic
VPA monotherapy in general and a separate blood genomic profile correlated
with seizure freedom. These expression patterns provide new insight
into previously undetected mechanisms of VPA anticonvulsant activity.},
issn = {1600-0404},
keywords = {epilepsy, seizure, anticonvulsant, Valproic Acid, carbamazepine, gene
expression, microarray, blood marker},
publisher = {Munksgaard International Publishers},
url = {http://dx.doi.org/10.1046/j.1600-0404.2003.00253.x}
}
@ARTICLE{Tang2008,
author = {Tang, Yi and Kitisin, Krit and Jogunoori, Wilma and Li, Cuiling and
Deng, Chu-Xia and Mueller, Susette C. and Ressom, Habtom W. and Rashid,
Asif and He, Aiwu Ruth and Mendelson, Jonathan S. and Jessup, John
M. and Shetty, Kirti and Zasloff, Michael and Mishra, Bibhuti and
Reddy, E. P. and Johnson, Lynt and Mishra, Lopa},
title = {Progenitor/stem cells give rise to liver cancer due to aberrant TGF-{beta}
and IL-6 signaling},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {2445--2450},
number = {7},
month = feb,
abstract = {Cancer stem cells (CSCs) are critical for the initiation, propagation,
and treatment resistance of multiple cancers. Yet functional interactions
between specific signaling pathways in solid organ "cancer stem cells,"
such as those of the liver, remain elusive. We report that in regenerating
human liver, two to four cells per 30,000-50,000 cells express stem
cell proteins Stat3, Oct4, and Nanog, along with the prodifferentiation
proteins TGF-{beta}-receptor type II (TBRII) and embryonic liver
fodrin (ELF). Examination of human hepatocellular cancer (HCC) reveals
cells that label with stem cell markers that have unexpectedly lost
TBRII and ELF. elf+/- mice spontaneously develop HCC; expression
analysis of these tumors highlighted the marked activation of the
genes involved in the IL-6 signaling pathway, including IL-6 and
Stat3, suggesting that HCC could arise from an IL-6-driven transformed
stem cell with inactivated TGF-{beta} signaling. Similarly, suppression
of IL-6 signaling, through the generation of mouse knockouts involving
a positive regulator of IL-6, Inter-alpha-trypsin inhibitor-heavy
chain-4 (ITIH4), resulted in reduction in HCC in elf+/- mice. This
study reveals an unexpected functional link between IL-6, a major
stem cell signaling pathway, and the TGF-{beta} signaling pathway
in the modulation of mammalian HCC, a lethal cancer of the foregut.
These experiments suggest an important therapeutic role for targeting
IL-6 in HCCs lacking a functional TGF-{beta} pathway.},
url = {http://www.pnas.org/cgi/content/abstract/105/7/2445}
}
@ARTICLE{Tang2004a,
author = {Tang, Yang and Lu, Aigang and Ran, Ruiqiong and Aronow, Bruce J.
and Schorry, Elizabeth K. and Hopkin, Robert J. and Gilbert, Donald
L. and Glauser, Tracy A. and Hershey, Andrew D. and Richtand, Neil
W. and Privitera, Michael and Dalvi, Arif and Sahay, Alok and Szaflarski,
Jerzy P. and Ficker, David M. and Ratner, Nancy and Sharp, Frank
R.},
title = {Human blood genomics: distinct profiles for gender, age and neurofibromatosis
type 1},
journal = {Molecular Brain Research},
year = {2004},
volume = {132},
pages = {155--167},
number = {2},
month = dec,
abstract = {Application of gene expression profiling to human diseases will be
limited by availability of tissue samples. It was postulated that
germline genetic defects affect blood cells to produce unique expression
patterns. This hypothesis was addressed by using a test neurological
disease-neurofibromatosis type 1 (NF1), an autosomal dominant genetic
disease caused by mutations of the NF1 gene at chromosome 17q11.2.
Oligonucleotide arrays were used to survey the blood gene expression
pattern of 12 NF1 patients compared to 96 controls. A group of genes
related to tissue remodeling, bone development and tumor suppression
were down-regulated in NF1 blood samples. In addition, there were
blood genomic patterns for gender and age: Y chromosome genes showing
higher expression in males, indicating a gene-dosage effect; and
genes related to lymphocyte functions showing higher expression in
children. The results suggest that genetic mutations can be manifested
at the transcriptional level in peripheral blood cells and blood
gene expression profiling may be useful for studying phenotypic differences
of human genetic diseases and possibly providing diagnostic and prognostic
markers.},
booktitle = {Neurogenomics},
issn = {0169-328X},
keywords = {Neurofibromatosis, Age, Gender, Genomics, Microarray, Blood, Gene
expression profiling, Marker},
url = {http://www.sciencedirect.com/science/article/B6T07-4BC2MB8-1/2/fe350fa827a21c59c8cdbeb326661620}
}
@ARTICLE{Tang2004b,
author = {Tang, Zhonghua and McGowan, Brian S. and Huber, Sally A. and McTiernan,
Charles F. and Addya, Sankar and Surrey, Saul and Kubota, Toru and
Fortina, Paolo and Higuchi, Yoshihiro and Diamond, Maura A. and Wyre,
Dwayne S. and Feldman, Arthur M.},
title = {Gene expression profiling during the transition to failure in TNF-[alpha]
over-expressing mice demonstrates the development of autoimmune myocarditis},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2004},
volume = {36},
pages = {515--530},
number = {4},
month = apr,
abstract = {Transgenic mice with cardiac-specific over-expression of tumor necrosis
factor-[alpha] (TNF1.6) progress to dilated heart failure. A significant
inflammatory response precedes functional deterioration, and may
contribute to cardiac damage in this model. To evaluate the underlying
molecular mechanisms, we assessed the gene expression in six groups
of mouse hearts defined by age, gender, and phenotype (n = 3/group)
using Affymetrix microarray analysis. Phenotype was defined as compensated
(in young TNF1.6) or decompensated (in older TNF1.6) via echocardiogram.
Of the >1000 transcripts altered in the compensated hearts (fold
change > 2, P < 0.05 vs. wild-type (WT)), 102 were identified as
immune response genes, 20 of which function in antigen presentation
and processing. When comparing the compensated and decompensated
hearts, >50 genes were differentially regulated, including seven
immunoglobulin genes. Real-time reverse transcriptase-polymerase
chain reaction and cDNA microarray confirmed the Affymetrix data.
Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells were identified
in both compensated and decompensated hearts. However, a large amount
of IgG was found deposited in areas devoid of B-lymphocytes in the
myocardium of decompensated TNF1.6 mice; no such accumulation was
seen in the compensated or age-matched controls. Furthermore, nuclei
density analyses showed a two-fold increase in the myocardium of
both compensated and decompensated TNF1.6 mice (vs. WT). This study
suggests that TNF-[alpha] over-expression activates not only the
inflammatory response, but also humoral immune responses within the
transgenic hearts. The autoimmune response occurs concomitantly with
cardiac decompensation and may participate in triggering the transition
to failure in TNF1.6 mice.},
issn = {0022-2828},
keywords = {Cytokines, Inflammation, Hypertrophy, Cardiomyopathy, Microarray,
Gene expression},
url = {http://www.sciencedirect.com/science/article/B6WK6-4BYRS5M-1/2/defba54e050b9e64e7204dcd6b22e11d}
}
@ARTICLE{Tang2006,
author = {Tang, Zhihui and Sahu, Surasri Nandan and Khadeer, Mohammed Abdul
and Bai, Guang and Franklin, Renty B. and Gupta, Anandarup},
title = {Overexpression of the ZIP1 zinc transporter induces an osteogenic
phenotype in mesenchymal stem cells},
journal = {Bone},
year = {2006},
volume = {38},
pages = {181--198},
number = {2},
month = feb,
abstract = {Zinc is an essential trace element that is involved in diverse metabolic
and signaling pathways. Zinc deficiency is associated with retardation
of bone growth. Previous in vitro studies have suggested a direct
effect of zinc on both the proliferation and differentiation of osteoblast-like
cells. However, the mechanisms for uptake of zinc into osteoblasts
have not been examined in detail. Several families of zinc transporters
have previously been characterized in mammalian cells; such transporters
function in the uptake, intracellular sequestration or efflux of
zinc. In the current study, we examined zinc transport in osteoprogenitor
cells and have attempted to define a functional role for a zinc transport
mechanism in osteogenic differentiation. We identified at least two
zinc transporters in both human mesenchymal stem cells (MSCs) and
in osteoblastic cells--the ubiquitous zinc transporter, ZIP1, and
LIV-1, which was previously characterized as a protein that is expressed
in breast cancer cells. The subcellular localization of both these
zinc transporters suggested distribution in both the plasma membrane
and also diffusely in the cytoplasm. During the differentiation process
of pluripotent MSCs into osteoblast-like cells, both zinc uptake
and expression of the ZIP1 protein were increased. An adenoviral-mediated
overexpression of ZIP1 in MSCs resulted in Alizarin-red-positive
mineralization and also increased expression of specific osteoblast-associated
markers, such as alkaline phosphatase, and of several osteoblast
differentiation genes, including osteopontin, Cbfa1/Runx2, promyelocytic
leukemia zinc finger and bone sialoprotein. An siRNA-mediated reduction
of ZIP1 protein expression in MSCs caused decreased zinc uptake and
inhibition of osteoblastic differentiation under osteogenic culture
conditions. Finally, following overexpression of ZIP1 in MSCs, cDNA
microarray analysis revealed differential regulation of several genes
associated with the proliferation of osteoprogenitor cells and osteoblast
differentiation. In conclusion, these studies provide important insights
into the role of a plasma membrane zinc transporter in the initiation
of an osteogenic lineage from MSCs.},
issn = {8756-3282},
keywords = {MSCs, mesenchymal stem cells, ZIP1, Zrt/Irt-like protein, LIV-1, BGM,
basal growth medium, OSM, osteogenic medium, OPN, osteopontin, ALP,
alkaline phosphatase, AR, Alizarin red, rAd, recombinant adenovirus},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4H7TD1B-1/2/21bf1e92f046b9d4838a5cda95945d07}
}
@ARTICLE{Tangrea2011,
author = {Tangrea, Michael A. and Mukherjee, Sumana and Gao, Bing and Markey,
Sanford P. and Du, Qiang and Armani, Michael and Kreitman, Matthew
S. and Rosenberg, Alex M. and Wallis, Benjamin S. and Eberle, Franziska
C. and Duncan, Francesca C. and Hanson, Jeffrey C. and Chuaqui, Rodrigo
F. and Rodriguez-Canales, Jaime and Emmert-Buck, Michael R.},
title = {Effect of Immunohistochemistry on Molecular Analysis of Tissue Samples:
Implications for Microdissection Technologies},
journal = {Journal of Histochemistry \& Cytochemistry},
year = {2011},
volume = {59},
pages = {591--600},
number = {6},
month = jun,
abstract = {Laser-based tissue microdissection is an important tool for the molecular
evaluation of histological sections. The technology has continued
to advance since its initial commercialization in the 1990s, with
improvements in many aspects of the process. More recent developments
are tailored toward an automated, operator-independent mode that
relies on antibodies as targeting probes, such as immuno-laser capture
microdissection or expression microdissection (xMD). Central to the
utility of expression-based dissection techniques is the effect of
the staining process on the biomolecules in histological sections.
To investigate this issue, the authors analyzed DNA, RNA, and protein
in immunostained, microdissected samples. DNA was the most robust
molecule, exhibiting no significant change in quality after immunostaining
but a variable 50% to 75% decrease in the total yield. In contrast,
RNA in frozen and ethanol-fixed, paraffin-embedded samples was susceptible
to hydrolysis and digestion by endogenous RNases during the initial
steps of staining. Proteins from immunostained tissues were successfully
analyzed by one-dimensional electrophoresis and mass spectrometry
but were less amenable to solution phase assays. Overall, the results
suggest investigators can use immunoguided microdissection methods
for important analytic techniques; however, continued improvements
in staining protocols and molecular extraction methods are key to
further advancing the capability of these methods.},
comment = {10.1369/0022155411404704},
url = {http://jhc.sagepub.com/cgi/content/abstract/59/6/591}
}
@ARTICLE{Tani2007,
author = {Tani, Hidenori and Kanagawa, Takahiro and Kurata, Shinya and Teramura,
Tatsuya and Nakamura, Kazunori and Tsuneda, Satoshi and Noda, Naohiro},
title = {Quantitative Method for Specific Nucleic Acid Sequences Using Competitive
Polymerase Chain Reaction with an Alternately Binding Probe},
journal = {Analytical Chemistry},
year = {2007},
volume = {79},
pages = {974-979},
number = {3},
doi = {10.1021/ac061506o},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac061506o},
url = {http://pubs.acs.org/doi/abs/10.1021/ac061506o}
}
@ARTICLE{Tani2009,
author = {Tani, Hidenori and Miyata, Ryo and Ichikawa, Kouhei and Morishita,
Soji and Kurata, Shinya and Nakamura, Kazunori and Tsuneda, Satoshi
and Sekiguchi, Yuji and Noda, Naohiro},
title = {Universal Quenching Probe System: Flexible, Specific, and Cost-Effective
Real-Time Polymerase Chain Reaction Method},
journal = {Analytical Chemistry},
year = {2009},
volume = {81},
pages = {5678-5685},
number = {14},
note = {PMID: 19530673},
doi = {10.1021/ac900414u},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac900414u},
url = {http://pubs.acs.org/doi/abs/10.1021/ac900414u}
}
@ARTICLE{Taniguchi2008,
author = {Taniguchi, Masaaki and Guan, Le Luo and Zhang, Bing and Dodson, Michael
V. and Okine, Erasmus and Moore, Stephen S.},
title = {Adipogenesis of bovine perimuscular preadipocytes},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {366},
pages = {54--59},
number = {1},
month = feb,
abstract = {In this study, non-transformed progeny adipofibroblasts, derived from
mature adipocyte dedifferentiation, was used as a novel in vitro
model to study adipogenic gene expression in cattle. Adipofibroblasts
from dedifferentiated mature perimuscular fat (PMF) tissue were cultured
with differentiation stimulants until the cells exhibited morphological
differentiation. Treated cells were harvested from day 2 to 16 for
RNA extraction, whereas control cells were cultured without addition
of stimulants. Results from time course gene expression assays by
quantitative real-time PCR revealed that peroxisome proliferator-activated
receptor gamma (PPAR-[gamma]), sterol regulatory element binding
protein 1 (SREBP-1) and their six down-stream genes were co-expressed
at day 2 post-differentiation induction. When compared to other adipogenesis
culture systems, the adipogenic gene expression of bovine PMF adipofibroblasts
culture was different, especially to the rodent model. Collectively,
these results demonstrated PPAR-[gamma] and SREBP-1 cooperatively
play a key role to regulate the re-differentiation of bovine adipofibroblasts,
during early conversion stages in vitro.},
issn = {0006-291X},
keywords = {Adipocyte, Bovine, Differentiation, Fat development, Gene expression,
PPAR-[gamma], SREBP-1, Transcription factor},
url = {http://www.sciencedirect.com/science/article/B6WBK-4R8KNK1-7/2/6583afa7a5109a69712d62b18a671dba}
}
@ARTICLE{Tannemaat2007,
author = {Tannemaat, Martijn R. and Korecka, Joanna and Ehlert, Erich M. E.
and Mason, Matthew R. J. and van Duinen, Sjoerd G. and Boer, Gerard
J. and Malessy, Martijn J. A. and Verhaagen, Joost},
title = {Human Neuroma Contains Increased Levels of Semaphorin 3A, Which Surrounds
Nerve Fibers and Reduces Neurite Extension In Vitro},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {14260--14264},
number = {52},
month = dec,
abstract = {Neuroma formation after peripheral nerve injury is detrimental to
functional recovery and is therefore a significant clinical problem.
The molecular basis for this phenomenon is not fully understood.
Here, we show that the expression of the chemorepulsive protein semaphorin
3A (sema3A), but not semaphorin 3F, is increased in human neuroma
tissue that has formed in severe obstetric brachial plexus lesions.
Sema3A is produced by fibroblasts in the epineurial space and appears
to be secreted into the extracellular matrix. It surrounds fascicles,
minifascicles, or single axons, suggesting a role in fasciculation
and inhibition of neurite outgrowth. Lentiviral vector-mediated knock-down
of Neuropilin 1, the receptor for sema3A, leads to increased neurite
outgrowth of F11 cells cultured on neuroma tissue, but not of F11
cells cultured on normal nerve tissue. These findings demonstrate
the putative inhibitory role of sema3A in human neuroma tissue. Our
observations are the first demonstration of the expression of sema3A
in human neural scar tissue and support a role for this protein in
the inhibition of axonal regeneration in injured human peripheral
nerves. These findings contribute to the understanding of the outgrowth
inhibitory properties of neuroma tissue.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/52/14260}
}
@ARTICLE{Tanney2008,
author = {Tanney, Austin and Oliver, Gavin and Farztdinov, Vadim and Kennedy,
Richard and Mulligan, Jude and Fulton, Ciaran and Farragher, Susan
and Field, John and Johnston, Patrick and Harkin, D Paul and Proutski,
Vitali and Mulligan, Karl},
title = {Generation of a non-small cell lung cancer transcriptome microarray},
journal = {BMC Medical Genomics},
year = {2008},
volume = {1},
pages = {20},
number = {1},
abstract = {BACKGROUND:Non-small cell lung cancer (NSCLC) is the leading cause
of cancer mortality worldwide. At present no reliable biomarkers
are available to guide the management of this condition. Microarray
technology may allow appropriate biomarkers to be identified but
present platforms are lacking disease focus and are thus likely to
miss potentially vital information contained in patient tissue samples.METHODS:A
combination of large-scale in-house sequencing, gene expression profiling
and public sequence and gene expression data mining were used to
characterise the transcriptome of NSCLC and the data used to generate
a disease-focused microarray – the Lung Cancer DSA research tool.RESULTS:Built
on the Affymetrix GeneChip platform, the Lung Cancer DSA research
tool allows for interrogation of ~60,000 transcripts relevant to
Lung Cancer, tens of thousands of which are unavailable on leading
commercial microarrays.CONCLUSION:We have developed the first high-density
disease specific transcriptome microarray. We present the array design
process and the results of experiments carried out to demonstrate
the array's utility. This approach serves as a template for the development
of other disease transcriptome microarrays, including non-neoplastic
diseases.},
doi = {10.1186/1755-8794-1-20},
issn = {1755-8794},
pubmedid = {18513400},
url = {http://www.biomedcentral.com/1755-8794/1/20}
}
@ARTICLE{Tantin2005,
author = {Tantin, Dean and Schild-Poulter, Caroline and Wang, Victoria and
Hache, Robert J.G. and Sharp, Phillip A.},
title = {The Octamer Binding Transcription Factor Oct-1 Is a Stress Sensor},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {10750--10758},
number = {23},
month = dec,
abstract = {The POU-domain transcription factor Oct-1 is widely expressed in adult
tissues and has been proposed to regulate a large group of target
genes. Microarray expression profiling was used to evaluate gene
expression changes in Oct-1-deficient mouse fibroblasts. A number
of genes associated with cellular stress exhibited altered expression.
Consistent with this finding, Oct-1-deficient fibroblasts were hypersensitive
to {gamma} radiation, doxorubicin, and hydrogen peroxide and harbored
elevated reactive oxygen species. Expression profiling identified
a second group of genes dysregulated in Oct-1-deficient fibroblasts
following irradiation, including many associated with oxidative and
metabolic stress. A number of these genes contain octamer sequences
in their immediate 5' regulatory regions, some of which are conserved
in human. These results indicate that Oct-1 modulates the activity
of genes important for the cellular response to stress.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/23/10750}
}
@ARTICLE{Tantiwong2010,
author = {Tantiwong, Puntip and Shanmugasundaram, Karthigayan and Monroy, Adriana
and Ghosh, Sangeeta and Li, Mengyao and DeFronzo, Ralph A. and Cersosimo,
Eugenio and Sriwijitkamol, Apiradee and Mohan, Sumathy and Musi,
Nicolas},
title = {NF-{kappa}B activity in muscle from obese and type 2 diabetic subjects
under basal and exercise-stimulated conditions},
journal = {Am J Physiol Endocrinol Metab},
year = {2010},
volume = {299},
pages = {E794--801},
number = {5},
month = nov,
abstract = {NF-{kappa}B is a transcription factor that controls the gene expression
of several proinflammatory proteins. Cell culture and animal studies
have implicated increased NF-{kappa}B activity in the pathogenesis
of insulin resistance and muscle atrophy. However, it is unclear
whether insulin-resistant human subjects have abnormal NF-{kappa}B
activity in muscle. The effect that exercise has on NF-{kappa}B activity/signaling
also is not clear. We measured NF-{kappa}B DNA-binding activity and
the mRNA level of putative NF-{kappa}B-regulated myokines interleukin
(IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples
from T2DM, obese, and lean subjects immediately before, during (40
min), and after (210 min) a bout of moderate-intensity cycle exercise.
At baseline, NF-{kappa}B activity was elevated 2.1- and 2.7-fold
in obese nondiabetic and T2DM subjects, respectively. NF-{kappa}B
activity was increased significantly at 210 min following exercise
in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-{kappa}B
activity did not change in T2DM. Exercise increased MCP-1 mRNA levels
significantly in the three groups, whereas IL-6 gene expression increased
significantly only in lean and obese subjects. MCP-1 and IL-6 gene
expression peaked at the 40-min exercise time point. We conclude
that insulin-resistant subjects have increased basal NF-{kappa}B
activity in muscle. Acute exercise stimulates NF-{kappa}B in muscle
from nondiabetic subjects. In T2DM subjects, exercise had no effect
on NF-{kappa}B activity, which could be explained by the already
elevated NF-{kappa}B activity at baseline. Exercise-induced MCP-1
and IL-6 gene expression precedes increases in NF-{kappa}B activity,
suggesting that other factors promote gene expression of these cytokines
during exercise.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/299/5/E794}
}
@ARTICLE{Tao2011,
author = {Tao, Jiong and Deng, Nian Tao and Ramnarayanan, Kalpana and Huang,
Baohua and Oh, Hue Kian and Leong, Siew Hong and Lim, Seong Soo and
Tan, Iain Beehuat and Ooi, Chia Huey and Wu, Jeanie and Lee, Minghui
and Zhang, Shenli and Rha, Sun Young and Chung, Hyun Cheol and Smoot,
Duane T. and Ashktorab, Hassan and Kon, Oi Lian and Cacheux, Valere
and Yap, Celestial and Palanisamy, Nallasivam and Tan, Patrick},
title = {CD44-SLC1A2 Gene Fusions in Gastric Cancer},
journal = {Science Translational Medicine},
year = {2011},
volume = {3},
pages = {77ra30--},
number = {77},
month = apr,
abstract = {Fusion genes are chimeric genes formed in cancers through genomic
aberrations such as translocations, amplifications, and rearrangements.
To identify fusion genes in gastric cancer, we analyzed regions of
chromosomal imbalance in a cohort of 106 primary gastric cancers
and 27 cell lines derived from gastric cancers. Multiple samples
exhibited genomic breakpoints in the 5' region of SLC1A2/EAAT2, a
gene encoding a glutamate transporter. Analysis of a breakpoint-positive
SNU16 cell line revealed expression of a CD44-SLC1A2 fusion transcript
caused by a paracentric chromosomal inversion, which was predicted
to produce a truncated but functional SLC1A2 protein. In primary
tumors, CD44-SLC1A2 gene fusions were detected in 1 to 2% of gastric
cancers, but not in adjacent matched normal gastric tissues. When
we specifically silenced CD44-SLC1A2, cellular proliferation, invasion,
and anchorage-independent growth were significantly reduced. Conversely,
CD44-SLC1A2 overexpression in gastric cells stimulated these pro-oncogenic
traits. CD44-SLC1A2 silencing caused significant reductions in intracellular
glutamate concentrations and sensitized SNU16 cells to cisplatin,
a commonly used chemotherapeutic agent in gastric cancer. We conclude
that fusion of the SLC1A2 gene coding region to CD44 regulatory elements
likely causes SLC1A2 transcriptional dysregulation, because tumors
expressing high SLC1A2 levels also tended to be CD44-SLC1A2-positive.
CD44-SLC1A2 may represent a class of gene fusions in cancers that
establish a pro-oncogenic metabolic milieu favoring tumor growth
and survival.},
comment = {10.1126/scitranslmed.3001423},
url = {http://stm.sciencemag.org/cgi/content/abstract/3/77/77ra30}
}
@ARTICLE{Tao2008,
author = {Tao, Kai and Fang, Min and Alroy, Joseph and Sahagian, G Gary},
title = {Imagable 4T1 model for the study of late stage breast cancer},
journal = {BMC Cancer},
year = {2008},
volume = {8},
pages = {228},
number = {1},
abstract = {BACKGROUND:The 4T1 mouse mammary tumor cell line is one of only a
few breast cancer models with the capacity to metastasize efficiently
to sites affected in human breast cancer. Here we describe two 4T1
cell lines modified to facilitate analysis of tumor growth and metastasis
and evaluation of gene function in vivo. New information regarding
the involvement of innate and acquired immunity in metastasis and
other characteristics of the model relevant to its use in the study
of late stage breast cancer are reported.METHODS:The lines were engineered
for stable expression of firefly luciferase to allow tracking and
quantitation of the cells in vivo. Biophotonic imaging was used to
characterize growth and metastasis of the lines in vivo and an improved
gene expression approach was used to characterize the basis for the
metastatic phenotype that was observed.RESULTS:Growth of cells at
the primary site was biphasic with metastasis detected during the
second growth phase 5–6 weeks after introduction of the cells. Regression
of growth, which occurred in weeks 3–4, was associated with extensive
necrosis and infiltration of leukocytes. Biphasic tumor growth did
not occur in BALB/c SCID mice indicating involvement of an acquired
immune response in the effect. Hematopoiesis in spleen and liver
and elevated levels of circulating leukocytes were observed at week
2 and increased progressively until death at week 6–8. Gene expression
analysis revealed an association of several secreted factors including
colony stimulatory factors, cytokines and chemokines, acute phase
proteins, angiogenesis factors and ECM modifying proteins with the
4T1 metastatic phenotype. Signaling pathways likely to be responsible
for production of these factors were also identified.CONCLUSION:The
production of factors that stimulate angiogenesis and ECM modification
and induce hematopoiesis, recruitment and activation of leukocytes
suggest that 4T1 tumor cells play a more direct role than previously
appreciated in orchestrating changes in the tumor environment conducive
to tumor cell dissemination and metastasis. The new cell lines will
greatly facilitate the study of late stage breast and preclinical
assessment of cancer drugs and other therapeutics particularly those
targeting immune system effects on tumor metastasis.},
doi = {10.1186/1471-2407-8-228},
issn = {1471-2407},
pubmedid = {18691423},
url = {http://www.biomedcentral.com/1471-2407/8/228}
}
@ARTICLE{Tao2007,
author = {Tao, Wenjing and Mallard, Bonnie},
title = {Differentially expressed genes associated with Staphylococcus aureus
mastitis of Canadian Holstein cows},
journal = {Veterinary Immunology and Immunopathology},
year = {2007},
volume = {120},
pages = {201--211},
number = {3-4},
month = dec,
abstract = {To study pathway specific gene expression within the immune-endocrine
axis of dairy cows with Staphylococcus aureus mastitis, mRNA was
collected from blood mononuclear cells (BMCs) and milk somatic cells
(MSCs) of cows (n = 7) identified as culture positive for S. aureus
and their matched negative control cows (n = 7) with no evidence
of S. aureus mastitis. Labeled cDNA probes derived from BMCs and
MSCs of infected and healthy cows were applied to a bovine immune-endocrine
cDNA array containing 167 genes. Genes with a log2 ratio >= 0.5 were
considered to be up-regulated and genes with a log2 ratio <= -0.5
to be down-regulated. In total, 22 genes were differentially displayed
in BMCs and 16 genes in MSCs of case versus controls. Expression
of selected genes in BMCs and MSCs were confirmed by real-time PCR.
The RT-PCR results were highly correlated with microarray measurements.
Some of these genes, such as interleukin (IL)-8 have been previously
implicated in other bacterial diseases, and are known to regulate
immune responses; whereas, others may reflect novel pathways or genes
involved in progressive mammary gland disease. For example, IL-18
was up-regulated in BMCs but not MSCs of mastitic quarters, while
IL-17 was more highly expressed in MSCs compared to BMCs. This study
identified a number of differentially expressed genes associated
with bovine S. aureus mastitis and demonstrates the intricacy of
the patterns of gene expression that influence host response to a
complex pathogen of significant relevance to both human and veterinary
medicine.},
issn = {0165-2427},
keywords = {Bovine, Staphylococcus aureus mastitis, Endocrine-immune microarray,
Gene expression, Immune response},
url = {http://www.sciencedirect.com/science/article/B6TD5-4P1G9F2-3/2/840180efcd102d9ce2cbb75ae91a2fe9}
}
@ARTICLE{Tao2006,
author = {Tao, Yun and Drabik, Kenneth A. and Waypa, Tonya S. and Musch, Mark
W. and Alverdy, John C. and Schneewind, Olaf and Chang, Eugene B.
and Petrof, Elaine O.},
title = {Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective
heat shock proteins in intestinal epithelial cells},
journal = {Am J Physiol Cell Physiol},
year = {2006},
volume = {290},
pages = {C1018--1030},
number = {4},
month = apr,
abstract = {Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce
heat shock protein (Hsp) expression in intestinal epithelial cells.
LGG-CM induces both Hsp25 and Hsp72 in a time- and concentration-dependent
manner. These effects are mediated by a low-molecular-weight peptide
that is acid and heat stable. DNA microarray experiments demonstrate
that Hsp72 is one of the most highly upregulated genes in response
to LGG-CM treatment. Real-time PCR and electrophoretic mobility shift
assay confirm that regulation of Hsp induction is at least in part
transcriptional in nature, involving heat shock factor-1. Although
Hsps are not induced for hours after exposure, transient exposure
to LGG-CM is sufficient to initiate the signal for Hsp induction,
suggesting that signal transduction pathways may be involved. Experiments
confirm that LGG-CM modulates the activity of certain signaling pathways
in intestinal epithelial cells by activating MAP kinases. Inhibitors
of p38 and JNK block the expression of Hsp72 normally induced by
LGG-CM. Functional studies indicate that LGG-CM treatment of gut
epithelial cells protects them from oxidant stress, perhaps by preserving
cytoskeletal integrity. By inducing the expression of cytoprotective
Hsps in gut epithelial cells, and by activating signal transduction
pathways, the peptide product(s) secreted by LGG may contribute to
the beneficial clinical effects attributed to this probiotic.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/290/4/C1018}
}
@ARTICLE{Tap2011,
author = {Tap, William D. and Eilber, Fritz C. and Ginther, Charles and Dry,
Sarah M. and Reese, Nicholas and Barzan-Smith, Kate and Chen, Hsiao-Wang
and Wu, Hong and Eilber, Frederick R. and Slamon, Dennis J. and Anderson,
Lee},
title = {Evaluation of well-differentiated/de-differentiated liposarcomas
by high-resolution oligonucleotide array-based comparative genomic
hybridization},
journal = {Genes, Chromosomes and Cancer},
year = {2011},
volume = {50},
pages = {95--112},
number = {2},
abstract = {Abstract Well-differentiated/de-differentiated liposarcomas (WDLS/DDLS)
encompass an intriguing disease model in which a temporal intersection
occurs between the malignant transformation of mesenchymal cells
and the process of adipogenesis. Deciphering the molecular events
that trigger and are characteristic of the intersection of these
oncogenic and normal processes is critical to affect the often morbid
and lethal consequences of malignant tumors of fat. High-resolution
genome-wide oligonucleotide array-based comparative genomic hybridization
(aCGH) with matched gene expression analyses was performed on seven
lipomas, one hibernoma, and 38 WD and DDLS to define and compare
the genomic events associated with these tumors. WD and DDLS had
complex karyotypes. On average, WDLS had 11.1 and DDLS had 22.7 chromosomal
copy number aberrations. All of the liposarcomas had 12q13-q15 amplifications
with varying peaks at CDK4 (12q14.1), HMGA2 (12q14.3), and MDM2 (12q15);
24% of the DDLS and no WDLS had 1p32.2 (JUN) amplifications; 33%
WDLS and 35% DDLS had 1q24.3 amplifications involving DNM3 and miR-214/miR-199a2;
24% of the liposarcomas had 6q23-q24 amplifications (including MAP3K5).
Amplifications in GLI1 (12q13.3), JUN, and MAP3K5 (6q23.3) were mutually
exclusive and occurred predominately in the DDLS. 6q amplifications
occurred primarily in retroperitoneal tumors and females represented
the majority of those patients who developed fatty tumors prior to
the age of 50 years old. This detailed genetic mapping provides insight
into the heterogeneity of WD and DDLS and the chromosomal and genetic
abnormalities that are present in and distinguish these mesenchymal
malignancies. © 2010 Wiley-Liss,Inc.},
doi = {10.1002/gcc.20835},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20835}
}
@ARTICLE{Taraktsoglou2011,
author = {Taraktsoglou, Maria and Szalabska, Urszula and Magee, David A. and
Browne, John A. and Sweeney, Torres and Gormley, Eamonn and MacHugh,
David E.},
title = {Transcriptional profiling of immune genes in bovine monocyte-derived
macrophages exposed to bacterial antigens},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {140},
pages = {130--139},
number = {1-2},
month = mar,
abstract = {The involvement of Toll-like receptors (TLRs) and other immune signalling
genes during challenge of bovine macrophages with bacterial products
derived from disease-causing bacteria in cattle was investigated.
An in vitro cell culture model of bovine monocyte derived macrophages
(MDM) was established and these cells were exposed to purified protein
derivative (PPD-b) derived from Mycobacterium bovis and to lipopolysachharide
(LPS) derived from Escherichia coli. Following 24 h incubation, total
RNA was extracted and expression of immune related genes was determined
by real time quantitative reverse transcription PCR (qRT-PCR). Expression
of a selection of genes spanning the TLR-2 and TLR-4 pathways, from
the initial activation of the receptors to the production of pro-inflammatory
cytokines and chemokines was determined. Results from repeat experiments
using MDM from seven different age-matched dairy cattle showed that
PPD-b treatment caused significant up-regulation of the TLR2 and
TLR4 genes and the expression profile of TLR adaptor molecules suggested
that this signalling is MYD88-dependent. Conversely, LPS caused significant
up-regulation of TLR4 via a MYD88-independent signalling pathway.
Significant up-regulation of genes involved with NF-[kappa]B signalling
was also detected in PPD-b- and LPS-treated samples accompanied by
the expression of pro-inflammatory cytokine (TNF, IL1B, IL6) and
chemokine genes (IL8, CCL5, CCL3). Overall, LPS challenge resulted
in a more marked up-regulation of immune-related genes. Furthermore,
the magnitude fold-change difference in gene expression suggests,
at least in part, that bovine macrophages produce IFN-[gamma] as
a result of LPS challenge.},
issn = {0165-2427},
keywords = {Cattle, Macrophage, Monocyte, Toll-like receptor, Real time quantitative
reverse transcription PCR, Purified protein derivative, Lipopolysaccharide},
url = {http://www.sciencedirect.com/science/article/pii/S0165242710004101}
}
@ARTICLE{Taraktsoglou2011a,
author = {Maria Taraktsoglou and Urszula Szalabska and David A. Magee and John
A. Browne and Torres Sweeney and Eamonn Gormley and David E. MacHugh},
title = {Transcriptional profiling of immune genes in bovine monocyte-derived
macrophages exposed to bacterial antigens},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {140},
pages = {130 - 139},
number = {1–2},
abstract = {The involvement of Toll-like receptors (TLRs) and other immune signalling
genes during challenge of bovine macrophages with bacterial products
derived from disease-causing bacteria in cattle was investigated.
An in vitro cell culture model of bovine monocyte derived macrophages
(MDM) was established and these cells were exposed to purified protein
derivative (PPD-b) derived from Mycobacterium bovis and to lipopolysachharide
(LPS) derived from Escherichia coli. Following 24 h incubation,
total RNA was extracted and expression of immune related genes was
determined by real time quantitative reverse transcription PCR (qRT-PCR).
Expression of a selection of genes spanning the TLR-2 and TLR-4 pathways,
from the initial activation of the receptors to the production of
pro-inflammatory cytokines and chemokines was determined. Results
from repeat experiments using MDM from seven different age-matched
dairy cattle showed that PPD-b treatment caused significant up-regulation
of the TLR2 and TLR4 genes and the expression profile of TLR adaptor
molecules suggested that this signalling is MYD88-dependent. Conversely,
LPS caused significant up-regulation of TLR4 via a MYD88-independent
signalling pathway. Significant up-regulation of genes involved with
NF-κB signalling was also detected in PPD-b- and LPS-treated samples
accompanied by the expression of pro-inflammatory cytokine (TNF,
IL1B, IL6) and chemokine genes (IL8, CCL5, CCL3). Overall, LPS challenge
resulted in a more marked up-regulation of immune-related genes.
Furthermore, the magnitude fold-change difference in gene expression
suggests, at least in part, that bovine macrophages produce IFN-γ
as a result of LPS challenge.},
doi = {10.1016/j.vetimm.2010.12.002},
issn = {0165-2427},
keywords = {Cattle},
url = {http://www.sciencedirect.com/science/article/pii/S0165242710004101}
}
@ARTICLE{Tararam2010,
author = {Tararam, Cibele Aparecida and Farias, Leonardo Paiva and Wilson,
R. Alan and Leite, Luciana Cezar de Cerqueira},
title = {Schistosoma mansoni Annexin 2: Molecular characterization and immunolocalization},
journal = {Experimental Parasitology},
year = {2010},
volume = {126},
pages = {146--155},
number = {2},
month = oct,
abstract = {We here describe the cloning and characterization of the Schistosoma
mansoni Annexin 2, previously identified in the tegument by proteomic
studies, and as an up-regulated gene in schistosomulum stage by microarray
data. In silico analysis predicts a conserved core containing four
repeat domains of Annexin (ANX) and a variable N-terminal region
similar to that described for mammalian isoforms. Real-time RT-PCR
and Western blot analysis determined that S. mansoni Annexin 2 is
significantly up-regulated in the transition from free-living cercaria
to schistosomulum and adult worm parasitic stages. Immunolocalization
experiments and tegument membrane preparations confirmed Annexin
2 as a protein mainly localized in the tegument of schistosomula
and adult worms. Furthermore, it binds to the tegument surface membranes
in a calcium-dependent manner. These results suggest that S. mansoni
Annexin 2 is closely associated to the tegument arrangement, being
a potential target for immune intervention.},
issn = {0014-4894},
keywords = {Annexin, Tegument, Schistosoma mansoni, Vaccine candidate, Ca+2-dependent
membrane-binding},
url = {http://www.sciencedirect.com/science/article/B6WFH-4YX7KK1-1/2/aeb2fe7d1cc134f8fda1eb6e721eab3a}
}
@ARTICLE{Tarasov2008,
author = {Tarasov, Valery Y. and Besir, Hüseyin and Schwaiger, Rita and Klee,
Kathrin and Furtwängler, Katarina and Pfeiffer, Friedhelm and Oesterhelt,
Dieter},
title = {A small protein from the bop–brp intergenic region of Halobacterium
salinarum contains a zinc finger motif and regulates bop and crtB1
transcription},
journal = {Molecular Microbiology},
year = {2008},
volume = {67},
pages = {772--780},
number = {4},
abstract = {Summary Bacteriorhodopsin, the photosynthetic protein of Halobacterium
salinarum, is optimally expressed under anaerobic growth conditions.
We identified Brz (OE3104F, bacteriorhodopsin-regulating zinc finger
protein), a new regulator of the bop gene. It is a small protein
with a zinc finger motif, encoded directly upstream of the bop gene
in the same orientation. Deletion of the brz gene caused a large
decrease of bop mRNA levels as shown by Northern blot and microarray
analysis. A similar effect was obtained by site-directed mutagenesis
of Cys and His residues in the zinc finger motif, indicating the
importance of this motif for the function of the protein. In silico
analysis of the genomes from H. salinarum and other archaea revealed
a large family of similar small zinc finger motif proteins, some
of which may also be involved in transcription regulation of their
adjacent genes.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2007.06081.x}
}
@ARTICLE{Tarassishin2011,
author = {Tarassishin, Leonid and Loudig, Olivier and Bauman, Avital and Shafit-Zagardo,
Bridget and Suh, Hyeon-Sook and Lee, Sunhee C.},
title = {Interferon regulatory factor 3 inhibits astrocyte inflammatory gene
expression through suppression of the proinflammatory miR-155 and
miR-155*},
journal = {Glia},
year = {2011},
volume = {59},
pages = {1911--1922},
number = {12},
abstract = {Astrocytes, together with microglia and macrophages, participate in
innate inflammatory responses in the CNS. Although inflammatory mediators
such as interferons generated by astrocytes may be critical in the
defense of the CNS, sustained unopposed cytokine signaling could
result in harmful consequences. Interferon regulatory factor 3 (IRF3)
is a transcription factor required for IFNβ production and antiviral
immunity. Most cells express low levels of IRF3 protein, and the
transcriptional mechanism that upregulates IRF3 expression is not
known. In this study, we explored the consequence of adenovirus-mediated
IRF3 gene transfer (Ad-IRF3) in primary human astrocytes. We show
that IRF3 transgene expression suppresses proinflammatory cytokine
gene expression upon challenge with IL-1/IFNγ and alters astrocyte
activation phenotype from a proinflammatory to an anti-inflammatory
one, akin to an M1–M2 switch in macrophages. This was accompanied
by the rescue of neurons from cytokine-induced death in glial-neuronal
co-cultures. Furthermore, Ad-IRF3 suppressed the expression of microRNA-155
and its star-form partner miR-155*, immunoregulatory miRNAs highly
expressed in multiple sclerosis lesions. Astrocyte miR-155/miR155*
were induced by cytokines and TLR ligands with a distinct hierarchy
and involved in proinflammatory cytokine gene induction by targeting
suppressor of cytokine signaling 1, a negative regulator of cytokine
signaling and potentially other factors. Our results demonstrate
a novel proinflammatory role for miR-155/miR-155* in human astrocytes
and suggest that IRF3 can suppress neuroinflammation through regulating
immunomodulatory miRNA expression. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/glia.21233},
issn = {1098-1136},
keywords = {interferon, human, microRNA, neuroinflammation, glia, cytokines},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.21233}
}
@ARTICLE{Tardin2009,
author = {Tardin, A. and Dominicé Dao, M. and Ninet, B. and Janssens, J.-P.},
title = {Conglomerado de Tuberculosis en una comunidad de inmigrantes: problemas
con la identificación de casos y perspectiva transcultural},
journal = {Tropical Medicine \& International Health},
year = {2009},
volume = {14},
pages = {995--1002},
number = {9},
abstract = {Summary Objectives  In a low incidence area for tuberculosis (TB),
a computerized database identified an unusually high proportion of
patients coming from one single country between 2004 and 2006. To
determine whether they constituted a cluster, whether clustering
was due to recent transmission, and to understand what undermined
the efficacy of the contact tracing procedure, we conducted a retrospective
study of all patients with TB from this country. Methods Mycobacterium
tuberculosis isolates of 15 TB cases originating from the same country
over a 2½ year period were analysed by restriction fragment length
polymorphism (RFLP) and/or Rep-PCR. To identify links between patients,
we revisited the social worker’s files, cross-matched contacts’
databases, and performed internet searches. A cultural evaluation
was conducted by an anthropologist and an expert physician, through
patient and community key informant interviews and a literature review.
Results  Genotyping confirmed that 11 of 15 patients had identical
isolates. Additional data revealed an unsuspected complex network
of social links between 9 of these 11 patients. The transcultural
evaluation pointed out the major obstacles to efficient contact tracing,
such as importance of social stigma related to TB, differences in
communication style and health beliefs, and linguistic barriers.
Conclusion  The combined finding of identical genotypes and important
social links between patients confirmed the suspicion of a TB cluster
due to recent transmission. The cultural evaluation helped to explain
the difficulties encountered during the contact tracing procedure,
and offered strategies to improve its efficacy despite the magnitude
of the social stigma attached to TB in this community.
Objectifs:  Dans une zone à faible incidence de la tuberculose
(TB), une base de données informatique a identifié une proportion
exceptionnellement élevée de patients provenant du même pays entre
2004 et 2006. Afin de déterminer s’ils constituent un même groupe,
si le regroupement est dûà une transmission récente et de comprendre
ce qui a compromis l’efficacité de la procédure de recherche
des contacts, nous avons mené une étude rétrospective sur tous
les patients atteints de TB provenant de ce pays.Méthodes:  Des
isolats de Mycobacterium tuberculosis de 15 cas de TB originaires
du même pays au cours d’une période de deux ans et demi ont été
analysés par polymorphisme de la taille des fragments de restriction
(RFLP) de l’ADN et/ou par Rep-PCR. Afin d’identifier les liens
entre les patients, nous avons revu les dossiers de l’assistant
social, comparé les bases de données des contacts et effectué
des recherches sur Internet. Une évaluation culturelle a été menée
par un anthropologue et un médecin expert, par le biais des informateurs
clés sur le patient et la collectivité et d’une revue de la littérature.Résultats: 
Le génotypage a confirmé que 11 des 15 patients avaient des isolats
identiques. Des données complémentaires ont révélé un réseau
complexe insoupçonné de liens sociaux entre 9 de ces 11 patients.
L’évaluation transculturelle a souligné les principaux obstacles
à l’efficacité de la recherche des contacts, tels que l’importance
de la stigmatisation sociale liée à la TB, les différences de
style de communication et des croyances sur la santé et les barrières
linguistiques.Conclusion:  La combinaison de la constatation des
génotypes identiques et des importants liens sociaux entre les patients
a confirmé la suspicion d’un regroupement de TB dûà une transmission
récente. L’évaluation culturelle a aidéà expliquer les difficultés
rencontrées lors de la procédure de recherche des contacts et a
proposé des stratégies pour améliorer son efficacité en dépit
de l’ampleur de la stigmatisation sociale attachée à la TB dans
la communauté.
Objetivos:  En un área con una baja incidencia de tuberculosis
(TB), mediante una base de datos computarizada se identificó una
proporción inusualmente alta de pacientes que provenÃan de un solo
paÃs entre el 2004 y 2006. Con el fin de determinar si podÃan constituirse
en un conglomerado, si la agrupación se debÃa a una reciente transmisión,
y con el fin de entender que minaba la eficacia del procedimiento
de seguimiento de contactos, condujimos un estudio retrospectivo
de todos los pacientes con TB de este paÃs.Métodos:  Cepas de
Mycobacterium tuberculosis, provenientes de 15 casos de TB originados
en el mismo paÃs durante un periodo de dos años y medio, fueron
analizadas mediante polimorfismo de longitud de fragmentos de restricción
(RFLP) y/o Rep-PCR. Con el fin de identificar el nexo entre pacientes,
se revisaron los archivos de trabajadores sociales, se compararon
con las bases de datos de contactos, y se realizaron búsquedas en
internet. Mediante entrevistas a informantes claves y la revisión
de literatura se hizo una evaluación cultural con un antropólogo
y un médico experto.Resultados:  El genotipaje confirmó que 11
de los 15 pacientes tenÃan cepas idénticas. Datos adicionales revelaron
un insospechada y compleja trama de nexos sociales entre 9 de estos
11 pacientes. La evaluación transcultural mostró los principales
obstáculos para el seguimiento eficiente de contactos, tales como
la importancia del estigma social relacionado con la TB, diferencias
en el estilo de comunicación y creencias sobre la salud, y barreras
lingüÃsticas.Conclusión:  El hallazgo combinado de genotipos
idénticos y los nexos sociales importantes entre pacientes, confirmaron
la sospecha de un conglomerado de TB debido a una reciente transmisión.
La evaluación cultural ayudó a explicar las dificultades encontradas
durante el procedimiento de seguimiento de contactos, y ofreció
estrategias para mejorar su eficacia a pesar de la magnitud del estigma
social que tiene la TB en esta comunidad.},
issn = {1365-3156},
keywords = {tuberculosis, contact tracing, genotyping, transcultural medicine,
tuberculose, recherche des contacts, génotypage, médecine transculturelle,
tuberculosis, seguimiento de contactos, genotipaje, medicina transcultural},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3156.2009.02325.x}
}
@ARTICLE{Tariq2011,
author = {Tariq, Muhammad A. and Kim, Hyunsung J. and Jejelowo, Olufisayo and
Pourmand, Nader},
title = {Whole-transcriptome RNAseq analysis from minute amount of total RNA},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {e120},
number = {18},
abstract = {RNA sequencing approaches to transcriptome analysis require a large
amount of input total RNA to yield sufficient mRNA using either poly-A
selection or depletion of rRNA. This feature makes it difficult to
miniaturize transcriptome analysis for greater efficiency. To address
this challenge, we devised and validated a simple procedure for the
preparation of whole-transcriptome cDNA libraries from a minute amount
(500 pg) of total RNA. We compared a single-sample library prepared
by this Ovation(R) RNA-Seq system with two available methods of mRNA
enrichment (TruSeqTM poly-A enrichment and RiboMinusTM rRNA depletion).
Using the Ovation(R) preparation method for a set of eight mouse
tissue samples, the RNA sequencing data obtained from two different
next-generation sequencing platforms (SOLiD and Illumina Genome Analyzer
IIx) yielded negligible rRNA reads (<3.5%) while retaining transcriptome
sequencing fidelity. We further validated the Ovation(R) amplification
technique by examining the resulting library complexity, reproducibility,
evenness of transcript coverage, 5' and 3' bias and platform-specific
biases. Notably, in this side-by-side comparison, SOLiD sequencing
chemistry is biased toward higher GC content of transcriptome and
Illumina Genome analyzer IIx is biased away from neutral to lower
GC content of the transcriptomics regions.},
doi = {10.1093/nar/gkr547},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/18/e120.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/18/e120}
}
@ARTICLE{Tarroni2012,
author = {Tarroni, Paola and Villa, Isabella and Mrak, Emanuela and Zolezzi,
Francesca and Mattioli, Michela and Gattuso, Claudio and Rubinacci,
Alessandro},
title = {Microarray analysis of 1,25(OH)2D3 regulated gene expression in human
primary osteoblasts},
journal = {Journal of Cellular Biochemistry},
year = {2012},
volume = {113},
pages = {640--649},
number = {2},
abstract = {Though extensive studies have been conducted, questions regarding
the molecular effectors and pathways underlying the regulatory role
of 1,25(OH)2D3 in human osteoblasts other than cell differentiation
and matrix protein production remain unanswered. This study aims
to identify genes and pathways that are modulated by 1,25(OH)2D3
treatment in human osteoblasts. Primary osteoblast cultures obtained
from human bone tissue samples were treated with 1,25(OH)2D3 (10−7 M)
for 24 h and their transcritptomes were profiled by microarray
analysis using the Affymetrix GeneChip®. Statistical analysis was
conducted to identify genes whose expression is significantly modulated
following 1,25(OH)2D3 treatment. One hundred and fifty-eight genes
were found to be differentially expressed. Of these, 136 were upregulated,
indicating clear transcriptional activation by 1,25(OH)2D3. Biostatistical
evaluation of microarray data by Ingenuity Pathways Analysis (IPA)
revealed a relevant modulation of genes involved in vitamin D metabolism
(CYP24), immune functions (CD14), neurotransmitter transporters (SLC1A1,
SLC22A3), and coagulation [thrombomodulin (THBD), tissue plasminogen
activator (PLAT), endothelial protein C receptor (PROCR), thrombin
receptor (F2R)]. We identified a restricted number of highly regulated
genes and confirmed their differential expression by real-time quantitative
PCR (RT qPCR). The present genome-wide microarray analysis on 1,25(OH)2D3-treated
human osteoblasts reveals an interplay of critical regulatory and
metabolic pathways and supports the hypothesis that 1,25(OH)2D3 can
modulate the coagulation process through osteoblasts, activates osteoclastogenesis
through inflammation signaling, modulates the effects of monoamines
by affecting their reuptake. J. Cell. Biochem. 113: 640–649, 2012.
© 2011 Wiley Periodicals, Inc.},
doi = {10.1002/jcb.23392},
issn = {1097-4644},
keywords = {1,25(OH)2D3, HUMAN PRIMARY OSTEOBLASTS, TRANSCRIPTIONAL PROFILING,
MICROARRAY},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.23392}
}
@ARTICLE{Tarry-Adkins2009,
author = {Tarry-Adkins, J. L. and Chen, J. H. and Smith, N. S. and Jones, R.
H. and Cherif, H. and Ozanne, S. E.},
title = {Poor maternal nutrition followed by accelerated postnatal growth
leads to telomere shortening and increased markers of cell senescence
in rat islets},
journal = {FASEB J},
year = {2009},
volume = {23},
pages = {1521--1528},
number = {5},
month = may,
abstract = {Low birth weight (LBW) followed by accelerated postnatal growth is
associated with increased risk of developing age-associated diseases
such as type 2 diabetes. Gestational protein restriction in rats
causes LBW, {beta}-cell dysfunction, and reduced longevity. These
effects may be mediated by accelerated cellular aging. This study
tested the hypothesis that LBW followed by rapid postnatal catch-up
growth leads to islet telomere shortening through alterations in
antioxidant defense capacity, stress/senescence marker proteins,
and DNA repair mechanisms at the gene expression level. We used our
rat model of gestational protein restriction (recuperated offspring)
and control offspring. Southern blotting revealed shorter (P<0.001)
islet telomeres in recuperated animals compared to controls. This
was associated with increased expression of peroxiredoxin 1 (P<0.05),
peroxiredoxin 3 (P<0.01), and heme oxygenase-1 (HO-1) (P<0.05), which
are up-regulated under stress conditions. MnSOD expression was significantly
(P<0.05) decreased in recuperated offspring, suggesting partial impairment
of mitochondrial antioxidant defenses. Markers of cellular senescence
p21 and p16 were also increased (P<0.01 and P<0.05, respectively)
in the recuperated group. We conclude that maternal diet influences
expression of markers of cellular stress and telomere length in pancreatic
islets. This may provide a mechanistic link between early nutrition
and growth and type 2 diabetes.--Tarry-Adkins, J. L., Chen, J. H.,
Smith, N. S., Jones, R. H., Cherif, H., Ozanne, S. E. Poor maternal
nutrition followed by accelerated postnatal growth leads to telomere
shortening and increased markers of cell senescence in rat islets.},
url = {http://www.fasebj.org/cgi/content/abstract/23/5/1521}
}
@ARTICLE{Tarry-Adkins2010,
author = {Tarry-Adkins, Jane L. and Chen, Jian-Hua and Jones, Richard H. and
Smith, Noel H. and Ozanne, Susan E.},
title = {Poor maternal nutrition leads to alterations in oxidative stress,
antioxidant defense capacity, and markers of fibrosis in rat islets:
potential underlying mechanisms for development of the diabetic phenotype
in later life},
journal = {FASEB J},
year = {2010},
volume = {24},
pages = {2762--2771},
number = {8},
month = aug,
abstract = {Low birth weight is associated with glucose intolerance, insulin resistance,
and type 2 diabetes (T2D) in later life. Good evidence indicates
that the environment plays an important role in this relationship.
However, the mechanisms underlying these relationships are defined
poorly. Islets are particularly susceptible to oxidative stress,
and this condition combined with fibrosis is thought to be instrumental
in T2D pathogenesis. Here we use our maternal low-protein (LP) rat
model to determine the effect of early diet on oxidative stress and
fibrosis in pancreatic islets of male offspring at 3 and 15 mo of
age. Islet xanthine oxidase (XO) expression was increased in 15-mo
LP offspring, which suggests increased oxidative-stress. Manganese
superoxide-dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD),
and heme oxygenase-1 (HO-1) (antioxidant enzymes) were reduced significantly
in LP offspring, which indicated impairment of oxidative defense.
Expression of fibrosis markers collagen I and collagen III also increased
in 15-mo LP offspring. Angiotensin II receptor type I (ATIIR1), induced
by hyperglycemia and oxidative-stress, was significantly up-regulated
in 15-mo LP offspring. Lipid peroxidation was also increased in 15-mo
LP animals. We conclude that maternal protein restriction causes
age-associated increased oxidative stress, impairment of oxidative
defense, and fibrosis. These findings provide mechanisms by which
suboptimal early nutrition can lead to T2D development later in life.--Tarry-Adkins,
J. L., Chen, J.-H., Jones, R. H., Smith, N. H., Ozanne, S. E. Poor
maternal nutrition leads to alterations in oxidative stress, antioxidant
defense capacity, and markers of fibrosis in rat islets: potential
underlying mechanisms for development of the diabetic phenotype in
later life.},
url = {http://www.fasebj.org/cgi/content/abstract/24/8/2762}
}
@ARTICLE{Tartagni2003,
author = {Tartagni, Marco and Altomare, Luigi and Guerrieri, Roberto and Fuchs,
Alexandra and Manaresi, Nicolò and Medoro, Gianni and Thewes, Roland},
title = {Microelectronic Chips for Molecular and Cell Biology},
journal = {Sensors Update},
year = {2003},
volume = {13},
pages = {155--200},
number = {1},
abstract = {Abstract 10.1002/seup.200390015.abs The development of microfabricated
devices manufactured in silicon, glass, or plastic materials is a
well-known trend in the research of novel biological techniques and
tools over the last two decades, resulting in a multitude of start-up
companies serving the pharmaceutical, biotechnology, and diagnostics
markets. However, the idea of implementing such devices on microelectronic
substrates has been introduced only recently. This chapter aims to
describe the state-of-the-art of microsystems for molecular and cell
biology produced in general purpose CMOS (complementary metal oxide
semiconductor) technology, emphasizing the advantages of this approach
along with their challenges and limitations. This chapter discusses
significant examples of fully tested devices in comparison with existing
state-of-the-art techniques.},
issn = {1616-8984},
keywords = {microelectronics, chips, molecular biology, cell biology},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/seup.200390015}
}
@ARTICLE{Tarun2008,
author = {Tarun, Alice S. and Peng, Xinxia and Dumpit, Ronald F. and Ogata,
Yuko and Silva-Rivera, Hilda and Camargo, Nelly and Daly, Thomas
M. and Bergman, Lawrence W. and Kappe, Stefan H. I.},
title = {A combined transcriptome and proteome survey of malaria parasite
liver stages},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {305--310},
number = {1},
month = jan,
abstract = {For 50 years since their discovery, the malaria parasite liver stages
(LS) have been difficult to analyze, impeding their utilization as
a critical target for antiinfection vaccines and drugs. We have undertaken
a comprehensive transcriptome analysis in combination with a proteomic
survey of LS. Green fluorescent protein-tagged Plasmodium yoelii
(PyGFP) was used to efficiently isolate LS-infected hepatocytes from
the rodent host. Genome-wide LS gene expression was profiled and
compared with other parasite life cycle stages. The analysis revealed
{approx}2,000 genes active during LS development, and proteomic analysis
identified 816 proteins. A subset of proteins appeared to be expressed
in LS only. The data revealed exported parasite proteins and LS metabolic
pathways including expression of FASII pathway enzymes. The FASII
inhibitor hexachlorophene and the antibiotics, tetracycline and rifampicin,
that target the apicoplast inhibited LS development, identifying
FASII and other pathways localized in the apicoplast as potential
drug targets to prevent malaria infection.},
url = {http://www.pnas.org/cgi/content/abstract/105/1/305}
}
@ARTICLE{Tarun2008a,
author = {Tarun, Salvador Zipagan, Jr and Schnaufer, Achim and Ernst, Nancy
Lewis and Proff, Rosemary and Deng, Junpeng and Hol, Wim and Stuart,
Kenneth},
title = {KREPA6 is an RNA-binding protein essential for editosome integrity
and survival of Trypanosoma brucei},
journal = {RNA},
year = {2008},
volume = {14},
pages = {347--358},
number = {2},
month = feb,
abstract = {Most mitochondrial mRNAs in kinetoplastid protozoa require post-transcriptional
RNA editing that inserts and deletes uridylates, a process that is
catalyzed by multiprotein editosomes. KREPA6 is the smallest of six
editosome proteins that have predicted oligonucleotide-binding (OB)
folds. Inactivation of KREPA6 expression results in disruption and
ultimate loss of [~]20S editosomes and inhibition of procyclic form
cell growth. Gel shift studies show that recombinant KREPA6 binds
RNA, but not DNA, with a preference for oligo-(U) whether on the
3' end of gRNA or as a (UU)12 homopolymer. Thus, KREPA6 is essential
for the structural integrity and presence of [~]20S editosomes and
for cell viability. It functions in RNA binding perhaps primarily
through the gRNA 3' oligo(U) tail. The significance of these findings
to key steps in editing is discussed.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/14/2/347}
}
@ARTICLE{Tarutina2006,
author = {Tarutina, Marina and Ryjenkov, Dmitri A. and Gomelsky, Mark},
title = {An Unorthodox Bacteriophytochrome from Rhodobacter sphaeroides Involved
in Turnover of the Second Messenger c-di-GMP},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {34751--34758},
number = {46},
month = nov,
abstract = {Bacteriophytochromes are bacterial photoreceptors that sense red/far
red light using the biliverdin chromophore. Most bacteriophytochromes
work as photoactivated protein kinases. The Rhodobacter sphaeroides
bacteriophytochrome BphG1 is unconventional in that it has GGDEF
and EAL output domains, which are involved, respectively, in synthesis
(diguanylate cyclase) and degradation (phosphodiesterase) of the
bacterial second messenger c-di-GMP. The GGDEF-EAL proteins studied
to date displayed either diguanylate cyclase or phosphodiesterase
activity but not both. To elucidate the function of BphG1, the holoprotein
was purified from an Escherichia coli overexpression system designed
to produce biliverdin. The holoprotein contained covalently bound
biliverdin and interconverted between the red (dark) and far red
(light-activated) forms. BphG1 had c-di-GMP-specific phosphodiesterase
activity. Unexpectedly for a photochromic protein, this activity
was essentially light-independent. BphG1 expressed in E. coli was
found to undergo partial cleavage into two species. The smaller species
was identified as the EAL domain of BphG1. It possessed c-di-GMP
phosphodiesterase activity. Surprisingly, the larger species lacking
EAL possessed diguanylate cyclase activity, which was dependent on
biliverdin and strongly activated by light. BphG1 therefore is the
first phytochrome with a non-kinase photoactivated enzymatic activity.
This shows that the photosensory modules of phytochromes can transmit
light signals to various outputs. BphG1 is potentially the first
"bifunctional" enzyme capable of both c-di-GMP synthesis and hydrolysis.
A model for the regulation of the "opposite" activities of BphG1
is presented.},
url = {http://www.jbc.org/cgi/content/abstract/281/46/34751}
}
@ARTICLE{Tassi2007,
author = {Tassi, Renata A. and Bignotti, Eliana and Rossi, Elisa and Falchetti,
Marcella and Donzelli, Carla and Calza, Stefano and Ravaggi, Antonella
and Bandiera, Elisabetta and Pecorelli, Sergio and Santin, Alessandro
D.},
title = {Overexpression of mammaglobin B in epithelial ovarian carcinomas},
journal = {Gynecologic Oncology},
year = {2007},
volume = {105},
pages = {578--585},
number = {3},
month = jun,
abstract = {Objective Mammaglobin B is a uteroglobin gene family member recently
found highly differentially expressed in serous papillary ovarian
cancer by gene expression profiling. In order to evaluate its potential
as a novel ovarian cancer biomarker, in this study we quantified
and compared Mammaglobin B expression in various histologic types
of epithelial ovarian carcinomas (EOC).Methods Mammaglobin B expression
was evaluated by real-time PCR and/or immunohistochemistry in fresh-frozen
biopsies and paraffin-embedded tissues derived from a total of 137
patients including 69 primary EOC with different histologies, 28
serous papillary omental metastasis, 8 borderline tumors, 26 benign
cystadenomas and 14 normal ovaries.Results High levels of Mammaglobin
B gene expression were detected in 100% (68 out of 68) of the ovarian
cancer biopsies tested by real-time PCR. In contrast, normal human
ovarian surface epithelium (HOSE) expressed negligible levels of
Mammaglobin B mRNA (EOC versus HOSE, p < 0.01). Although Mammaglobin
B gene expression levels were higher in endometrioid, mucinous and
undifferentiated tumors when compared to serous papillary tumors,
clear cell tumors and those with mixed histology, these differences
were not statistically significant. In agreement with real-time PCR
results, EOC were found to express significantly higher levels of
Mammaglobin B protein when compared to normal ovaries and benign
cystadenomas (p < 0.01). However, only 29 out of 68 (42%) of the
EOC samples found positive for Mammaglobin B by real-time PCR showed
immunoreactivity by IHC.Conclusions Mammaglobin B gene is highly
expressed in EOC and may represent a novel molecular marker for multiple
histological types of ovarian cancer. Additional studies to evaluate
the clinical utility of Mammaglobin B as a diagnostic and/or therapeutic
target in ovarian cancer are warranted.},
issn = {0090-8258},
keywords = {Mammaglobin B, Epithelial ovarian cancer, qRT-PCR, Ovarian tumor marker},
url = {http://www.sciencedirect.com/science/article/B6WG6-4N6FNRV-1/2/46fa1e4bed36ed8df2f2cc4ea6392249}
}
@ARTICLE{TASSI2008,
author = {TASSI, R.A. and BIGNOTTI, E. and FALCHETTI, M. and CALZA, S. and
RAVAGGI, A. and ROSSI, E. and MARTINELLI, F. and BANDIERA, E. and
PECORELLI, S. and SANTIN, A.D.},
title = {Mammaglobin B expression in human endometrial cancer},
journal = {International Journal of Gynecological Cancer},
year = {2008},
volume = {18},
pages = {1090--1096},
number = {5},
abstract = {Abstract Mammaglobin B (MGB-2) is an uteroglobin gene family member
recently found highly differentially expressed in ovarian cancer
by gene expression profiling. To evaluate its potential as a novel
endometrial cancer biomarker, in this study we quantified and compared
MGB-2 expression at messenger RNA and protein levels in endometrial
tumors (endometrioid endometrial cancer [EEC]) with different grades
of differentiation. MGB-2 expression was evaluated by real-time polymerase
chain reaction (PCR) and immunohistochemistry (IHC) in fresh frozen
biopsies and paraffin-embedded tissues derived from a total of 70
patients including 50 primary EEC and 20 normal endometria (NECs).
High levels of MGB-2 gene expression were detected in 10 of 11 EEC
G1 cases (91%), 16 of 17 EEC G2 cases (94%), and 6 of 22 EEC G3 cases
(27%) by real-time PCR. In contrast, normal endometrial cells expressed
low to negligible levels of MGB-2 by real-time PCR (P = 0.002 EEC
vs NEC). Well- and moderately differentiated EECs overexpressed MGB-2
gene at significant higher levels when compared to NECs (P < 0.01).
Pairwise differences between both G2 and G1 vs G3 cases for MGB-2
relative gene expression values were also statistically significant
(G2 vs G3 P < 0.001, G1 vs G3 P = 0.016). MGB-2 protein expression
was detected in 31 (86%) of 36 EEC and 0 of 5 atrophic NEC controls,
while seven of eight (88%) of the proliferative/secretory/hyperplastic
NECs focally expressed MGB-2 by IHC. MGB-2 is highly expressed in
EEC, particularly in well- and moderately differentiated tumors,
and may represent a novel molecular marker for EEC.},
issn = {1525-1438},
keywords = {differential expression, endometrioid endometrial cancer, mammaglobin
B, tumor marker},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1525-1438.2007.01137.x}
}
@ARTICLE{TASSI2008a,
author = {TASSI, R.A. and BIGNOTTI, E. and FALCHETTI, M. and RAVANINI, M. and
CALZA, S. and RAVAGGI, A. and BANDIERA, E. and FACCHETTI, F. and
PECORELLI, S. and SANTIN, A.D.},
title = {Claudin-7 expression in human epithelial ovarian cancer},
journal = {International Journal of Gynecological Cancer},
year = {2008},
volume = {18},
pages = {1262--1271},
number = {6},
abstract = {Abstract Claudin-7 (CLDN-7) is a tight junction protein recently found
highly differentially expressed in ovarian carcinoma. To evaluate
its potential as a novel biomarker, in this study, we quantified
and compared claudin-7 expression at messenger RNA and protein level
in 110 patients harboring various histologic types of epithelial
ovarian carcinomas (EOC). CLDN-7 transcript was found significantly
overexpressed in both primary and metastatic EOCs compared to normal
human ovarian surface epithelium cell lines (fold change = 111.4,
P < 0.001) by reverse transcription–polymerase chain reaction.
At the protein level, CLDN-7 expression was found significantly higher
in tumors of primary and metastatic origin when compared to normal
ovaries (P < 0.001), regardless of the histologic type, the grade
of differentiation, and the pathologic stage of the disease (P =
0.12). Moreover, a strong immunoreactivity for CLDN-7 was detected
in EOC cells present in ascites fluids, whereas ascites-derived inflammatory
cells, histiocytes, and reactive mesothelial cells were negative.
Finally, immunohistochemical expression of CLDN-7 was observed in
several human normal epithelial control tissues analyzed. CLDN-7
is significantly overexpressed in all main histologic types of EOC
and in single neoplastic cells disseminated in peritoneal cavity
and pleural effusions, suggesting its potential role as novel diagnostic
marker in ovarian cancer. Despite widespread expression of CLDN-7
in several human normal tissues, the high density of CLDN-7 molecules,
their membranous localization on EOC cells, and their lack of expression
on the celomic epithelium in the peritoneal cavity suggest that this
target could be potentially suitable for antibody-mediated localized
therapies of ovarian adenocarcinoma.},
issn = {1525-1438},
keywords = {Claudin-7 (CLDN-7), differential gene expression, epithelial ovarian
cancer, immunohistochemistry, ovarian tumor marker, tight junctions,
quantitative reverse transcription–polymerase chain reaction},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1525-1438.2008.01194.x}
}
@ARTICLE{Tassi2009,
author = {Tassi, Renata and Calza, Stefano and Ravaggi, Antonella and Bignotti,
Eliana and Odicino, Franco and Tognon, Germana and Donzelli, Carla
and Falchetti, Marcella and Rossi, Elisa and Todeschini, Paola and
Romani, Chiara and Bandiera, Elisabetta and Zanotti, Laura and Pecorelli,
Sergio and Santin, Alessandro},
title = {Mammaglobin B is an independent prognostic marker in epithelial ovarian
cancer and its expression is associated with reduced risk of disease
recurrence},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {253},
number = {1},
abstract = {BACKGROUND:Traditional prognostic factors in epithelial ovarian cancer
(EOC) are inadequate in predicting recurrence and long-term prognosis,
but genome-wide cancer research has recently provided multiple potentially
useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has
been selected from our previous microarray analysis performed on
19 serous papillary epithelial ovarian cancers and its expression
has been further investigated on multiple histological subtypes,
both at mRNA and protein level. Since, to date, there is no information
available on the prognostic significance of MGB-2 expression in cancer,
the aim of this study was to determine its prognostic potential on
survival in a large cohort of well-characterized EOC patients.METHODS:MGB-2
expression was evaluated by quantitative real time-PCR in fresh-frozen
tissue biopsies and was validated by immunohistochemistry in matched
formalin fixed-paraffin embedded tissue samples derived from a total
of 106 EOC patients and 27 controls. MGB-2 expression was then associated
with the clinicopathologic features of the tumors and was correlated
with clinical outcome.RESULTS:MGB-2 expression was found significantly
elevated in EOC compared to normal ovarian controls, both at mRNA
and protein level. A good correlation was detected between MGB-2
expression data obtained by the two different techniques. MGB-2 expressing
tumors were significantly associated with several clinicopathologic
characteristics defining a less aggressive tumor behavior. Univariate
survival analysis revealed a decreased risk for cancer-related death,
recurrence and disease progression in MGB-2-expressing patients (p
< 0.05). Moreover, multivariate analysis indicated that high expression
levels of MGB-2 transcript (HR = 0.25, 95%, 0.08–0.75, p = 0.014)
as well as positive immunostaining for the protein (HR = 0.41, 95%CI,
0.17–0.99, p = 0.048) had an independent prognostic value for disease-free
survival.CONCLUSION:This is the first report documenting that MGB-2
expression characterizes less aggressive forms of EOC and is correlated
with a favorable outcome. These findings suggest that the determination
of MGB-2, especially at molecular level, in EOC tissue obtained after
primary surgery can provide additional prognostic information about
the risk of recurrence.},
doi = {10.1186/1471-2407-9-253},
issn = {1471-2407},
pubmedid = {19635143},
url = {http://www.biomedcentral.com/1471-2407/9/253}
}
@ARTICLE{Tasso2012,
author = {Roberta Tasso and Massimiliano Gaetani and Erica Molino and Angela
Cattaneo and Massimiliano Monticone and Angela Bachi and Ranieri
Cancedda},
title = {The role of bFGF on the ability of MSC to activate endogenous regenerative
mechanisms in an ectopic bone formation model},
journal = {Biomaterials},
year = {2012},
volume = {33},
pages = {2086 - 2096},
number = {7},
abstract = {The view depicting bone marrow (BM)-derived mesenchymal stem cells
(MSC) as a uniform population differentiating into new-tissue builder
cells is evolving toward the concept of a heterogeneous population
of stem/progenitor cells secreting bioactive molecules, and contributing
to establish an on-site regenerative microenvironment. We report
that in an ectopic bone formation model the intrinsic MSC capability
to activate endogenous regenerative mechanisms is critically dependent
on the commitment level of implanted MSC. We demonstrate that the
presence of bFGF in the culture medium during mouse MSC expansion
in vitro is the key factor for the selection of subpopulations inducing
host regenerative responses. We developed a novel strategy combining
SILAC-LC-MS/MS quantitative proteomics of conditioned culture media
and gene expression profiling to disentangle the major role of MSC
in modulating the microenvironment toward the damage resolution.
The correspondence between results provided by the applied techniques
proved that the most statistically significant biological processes
favored by the bFGF treatment were carried out by secreted factors.
In particular, the immune response, the inflammatory response, the
response to wounding and chemotaxis were all upregulated in bFGF-selected
MSC. We propose these processes as majorly involved in activating
the endogenous responses triggered by trophic effects of implanted
bFGF-selected MSC.},
doi = {10.1016/j.biomaterials.2011.11.043},
issn = {0142-9612},
keywords = {Bone regeneration},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211013974}
}
@ARTICLE{Tassone2011,
author = {Tassone, Flora and De Rubeis, Silvia and Carosi, Chiara and La Fata,
Giorgio and Serpa, Gisele and Raske, Christopher and Willemsen, Rob
and Hagerman, Paul J. and Bagni, Claudia},
title = {Differential usage of transcriptional start sites and polyadenylation
sites in FMR1 premutation alleles},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {6172-6185},
number = {14},
abstract = {5'- and 3'-untranslated regions (UTRs) are important regulators of
gene expression and play key roles in disease progression and susceptibility.
The 5'-UTR of the fragile X mental retardation 1 (FMR1) gene contains
a CGG repeat element that is expanded (>200 CGG repeats; full mutation)
and methylated in fragile X syndrome (FXS), the most common form
of inherited intellectual disability (ID) and known cause of autism.
Significant phenotypic involvement has also emerged in some individuals
with the premutation (55-200 CGG repeats), including fragile X-associated
premature ovarian insufficiency (FXPOI) in females, and the neurodegenerative
disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), in
older adult carriers. Here, we show that FMR1 mRNA in human and mouse
brain is expressed as a combination of multiple isoforms that use
alternative transcriptional start sites and different polyadenylation
sites. Furthermore, we have identified a novel human transcription
start site used in brain but not in lymphoblastoid cells, and have
detected FMR1 isoforms generated through the use of both canonical
and non-canonical polyadenylation signals. Importantly, in both human
and mouse, a specific regulation of the UTRs is observed in brain
of FMR1 premutation alleles, suggesting that the transcript variants
may play a role in premutation-related pathologies.},
doi = {10.1093/nar/gkr100},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/14/6172.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/14/6172}
}
@ARTICLE{Tatebe2010,
author = {Tatebe, Ken and Zeytun, Ahmet and Ribeiro, Ruy and Hoffmann, Robert
and Harrod, Kevin and Forst, Christian},
title = {Response network analysis of differential gene expression in human
epithelial lung cells during avian influenza infections},
journal = {BMC Bioinformatics},
year = {2010},
volume = {11},
pages = {170},
number = {1},
abstract = {BACKGROUND:The recent emergence of the H5N1 influenza virus from avian
reservoirs has raised concern about future influenza strains of high
virulence emerging that could easily infect humans. We analyzed differential
gene expression of lung epithelial cells to compare the response
to H5N1 infection with a more benign infection with Respiratory Syncytial
Virus (RSV). These gene expression data are then used as seeds to
find important nodes by using a novel combination of the Gene Ontology
database and the Human Network of gene interactions. Additional analysis
of the data is conducted by training support vector machines (SVM)
with the data and examining the orientations of the optimal hyperplanes
generated.RESULTS:Analysis of gene clustering in the Gene Ontology
shows no significant clustering of genes unique to H5N1 response
at 8 hours post infection. At 24 hours post infection, however, a
number of significant gene clusters are found for nodes representing
"immune response" and "response to virus" terms. There were no significant
clusters of genes in the Gene Ontology for the control (Mock) or
RSV experiments that were unique relative to the H5N1 response. The
genes found to be most important in distinguishing H5N1 infected
cells from the controls using SVM showed a large degree of overlap
with the list of significantly regulated genes. However, though none
of these genes were members of the GO clusters found to be significant.CONCLUSIONS:Characteristics
of H5N1 infection compared to RSV infection show several immune response
factors that are specific for each of these infections. These include
faster timescales within the cell as well as a more focused activation
of immunity factors. Many of the genes that are found to be significantly
expressed in H5N1 response relative to the control experiments are
not found to cluster significantly in the Gene Ontology. These genes
are, however, often closely linked to the clustered genes through
the Human Network. This may suggest the need for more diverse annotations
of these genes and verification of their action in immune response.},
doi = {10.1186/1471-2105-11-170},
issn = {1471-2105},
pubmedid = {20370926},
url = {http://www.biomedcentral.com/1471-2105/11/170}
}
@ARTICLE{Tategu2008,
author = {Tategu, Moe and Nakagawa, Hiroki and Hayashi, Reiko and Yoshida,
Kenichi},
title = {Transcriptional co-factor CDCA4 participates in the regulation of
JUN oncogene expression},
journal = {Biochimie},
year = {2008},
volume = {90},
pages = {1515--1522},
number = {10},
month = oct,
abstract = {CDCA4, a member of the TRIP-Br transcriptional co-factor family, has
been shown to possess a unique role in regulating the transcriptional
activities of p53 as well as E2F1 transcription factors. In this
study, we aimed to identify a pivotal transcriptional target gene
regulated by CDCA4, so we suppressed CDCA4 expression by CDCA4-specific
short interference RNA (siRNA) in HeLa cells, and then performed
a DNA microarray analysis. Among the identified genes, we focused
on JUN, 14-3-3eta, and IL6ST (gp130) mRNAs which were up-regulated
in CDCA4-specific siRNA-transfected cells compared to control siRNA-transfected
cells. We confirmed that JUN, 14-3-3eta, and IL6ST proteins were
up-regulated when cells were transfected with CDCA4-specific siRNA.
14-3-3eta and IL6ST protein levels were unchanged upon on transfection
of cells with JUN-specific siRNA, indicating that 14-3-3eta and IL6ST
genes are not a direct target of JUN. Serine 63 and 73 phosphorylation
of JUN was unchanged when cells were transfected with CDCA4-specific
siRNA. In addition, JUN-driven reporter activity was unaffected by
CDCA4 co-transfection, suggesting that CDCA4 affects solely JUN mRNA
expression. Finally, by preparing various JUN promoter reporter constructs,
we minimized the JUN promoter sequence that was affected by CDCA4
co-expression. Together, these results add an important role of CDCA4
in the context of transcriptional regulation and cell fate determination
through the JUN oncogene.},
issn = {0300-9084},
keywords = {Transcriptional regulation, Jun, Promoter, DNA microarray},
url = {http://www.sciencedirect.com/science/article/B6VRJ-4SNGM9R-1/2/38168c331e6154c21f367b24ae8ea55d}
}
@ARTICLE{Tattersall2005,
author = {Tattersall, Elizabeth A.R. and Ergul, Ali and AlKayal, Fadi and DeLuc,
Laurent and Cushman, John C. and Cramer, Grant R.},
title = {Comparison of Methods for Isolating High-Quality RNA from Leaves
of Grapevine},
journal = {Am. J. Enol. Vitic.},
year = {2005},
volume = {56},
pages = {400--406},
number = {4},
month = dec,
abstract = {High concentrations of polyphenols and polysaccharides make it challenging
to extract high-quality RNA from grape organs. To determine an optimal
protocol for grape leaves, 15 different methods of RNA extraction
were evaluated based on cost, time to complete the extraction, and
quality of the RNA isolated. The addition of specific compounds to
the extraction buffer to remove polyphenols and polysaccharides is
often critical for downstream applications such as polymerase chain
reaction (PCR) and microarray hybridization. RNA quality was assessed
using spectrophotometric methods, formaldehyde-agarose gel electrophoresis,
reverse transcription (RT)-PCR reactions, and Agilent 2100 Bioanalyzer.
Large differences in RNA yield and quality among protocols were found.
Some protocols that are commonly used for other species did not yield
usable RNA from grapevine leaves. The optimum methods were Tris-lithium
chloride, which, while relatively time-consuming, gave consistently
high yields of quality RNA at very low cost and was suitable for
PCR and microarray hybridization, and RNeasy Midi + polyethylene
glycol, which rapidly provided high-quality RNA, but with lower yields.},
url = {http://www.ajevonline.org/cgi/content/abstract/56/4/400}
}
@ARTICLE{Taub2011,
author = {Taub, Mitchell E. and Mease, Kirsten and Sane, Rucha S. and Watson,
Cory A. and Chen, Liangfu and Ellens, Harma and Hirakawa, Brad and
Reyner, Eric L. and Jani, Marton and Lee, Caroline A.},
title = {Digoxin Is Not a Substrate for Organic Anion-Transporting Polypeptide
Transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but Is a Substrate
for a Sodium-Dependent Transporter Expressed in HEK293 Cells},
journal = {Drug Metab. Dispos.},
year = {2011},
volume = {39},
pages = {2093-2102},
number = {11},
abstract = {Digoxin, an orally administered cardiac glycoside cardiovascular drug,
has a narrow therapeutic window. Circulating digoxin levels (maximal
concentration of [~]1.5 ng/ml) require careful monitoring, and the
potential for drug-drug interactions (DDI) is a concern. Increases
in digoxin plasma exposure caused by inhibition of P-glycoprotein
(P-gp) have been reported. Digoxin has also been described as a substrate
of various organic anion-transporting polypeptide (OATP) transporters,
posing a risk that inhibition of OATPs may result in a clinically
relevant DDI similar to what has been observed for P-gp. Although
studies in rats have shown that Oatps contribute to the disposition
of digoxin, the role of OATPs in the disposition of digoxin in humans
has not been clearly defined. Using two methods, Boehringer Ingelheim,
GlaxoSmithKline, Pfizer, and Solvo observed that digoxin is not a
substrate of OATP1A2, OATP1B1, OATP1B3, and OATP2B1. However, digoxin
inhibited the uptake of probe substrates of OATP1B1 (IC50 of 47 M),
OATP1B3 (IC50 > 8.1 M), and OATP2B1 (IC50 > 300 M), but not OATP1A2
in transfected cell lines. It is interesting to note that digoxin
is a substrate of a sodium-dependent transporter endogenously expressed
in HEK293 cells because uptake of digoxin was significantly greater
in cells incubated with sodium-fortified media compared with incubations
conducted in media in which sodium was absent. Thus, although digoxin
is not a substrate for the human OATP transporters evaluated in this
study, in addition to P-gp-mediated efflux, its uptake and pharmacokinetic
disposition may be partially facilitated by a sodium-dependent transporter.},
doi = {10.1124/dmd.111.040816},
eprint = {http://dmd.aspetjournals.org/cgi/reprint/39/11/2093.pdf},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/39/11/2093}
}
@ARTICLE{Tauris2009,
author = {Tauris, Birgitte and Borg, Soren and Gregersen, Per L. and Holm,
Preben B.},
title = {A roadmap for zinc trafficking in the developing barley grain based
on laser capture microdissection and gene expression profiling},
journal = {J. Exp. Bot.},
year = {2009},
volume = {60},
pages = {1333--1347},
number = {4},
month = mar,
abstract = {Nutrients destined for the developing cereal grain encounter several
restricting barriers on their path towards their final storage sites
in the grain. In order to identify transporters and chelating agents
that may be involved in transport and deposition of zinc in the barley
grain, expression profiles have been generated of four different
tissue types: the transfer cells, the aleurone layer, the endosperm,
and the embryo. Cells from these tissues were isolated with the laser
capture microdissection' technology and the extracted RNA was subjected
to three rounds of T7-based amplification. The amplified RNA was
subsequently hybridized to Affymetrix 22K Barley GeneChips. Due to
the short average length of the amplified transcripts and the positioning
of numerous probe sets at locations more than 400 base pairs (bp)
from the poly(A)-tail, a normalization approach was used where the
probe positions were taken into account. On the basis of the expression
levels of a number of metal homeostasis genes, a working model is
proposed for the translocation of zinc from the phloem to the storage
sites in the developing grain.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/60/4/1333}
}
@ARTICLE{Tauzin2007,
author = {Tauzin, Loic and Graf, Christine and Sun, Mei and Rovina, Philipp
and Bouveyron, Nicolas and Jaritz, Markus and Winiski, Anthony and
Hartmann, Nicole and Staedtler, Frank and Billich, Andreas and Baumruker,
Thomas and Zhang, Mei and Bornancin, Frederic},
title = {Effects of ceramide-1-phosphate on cultured cells: dependence on
dodecane in the vehicle},
journal = {J. Lipid Res.},
year = {2007},
volume = {48},
pages = {66--76},
number = {1},
month = jan,
abstract = {Ceramide-1-phosphate (C1P), the product of ceramide kinase, is a sphingophospholipid
with recently recognized signaling properties. In particular, it
was reported to be mitogenic and capable of direct stimulation of
cytosolic phospholipase A2{alpha}. Much of the present knowledge
has relied on the use of C1P of various acyl chain lengths, together
with diverse protocols to deliver it to cultured cells. A mixture
of ethanol (or methanol) with dodecane, as the vehicle, has become
popular. However, the contribution of this solvent to the observed
effects of C1P has not been documented. Here, we show that addition
of C1P in ethanol-dodecane to culture medium leads to irreversible
cytotoxic effects. These culminate in mitochondrial swelling, vacuole
formation, and cell death. Not only the toxicity of C1P, but also
its ability to trigger prostaglandin E2 release, is fully dependent
upon addition of a premade C1P-dodecane mixture. Furthermore, we
show that these effects are not restricted to C1P. They result from
the capacity of dodecane to interact with phospholipids; hence, they
go undetected with a vehicle control. This study should raise awareness
about the use of dodecane for phospholipid delivery and, in turn,
help in unraveling C1P signaling, which is still poorly understood.},
url = {http://www.jlr.org/cgi/content/abstract/48/1/66}
}
@ARTICLE{Tavakoli2009,
author = {Tavakoli, Tahereh and Xu, Xiangru and Derby, Eric and Serebryakova,
Yevgeniya and Reid, Yvonne and Rao, Mahendra and Mattson, Mark and
Ma, Wu},
title = {Self-renewal and differentiation capabilities are variable between
human embryonic stem cell lines I3, I6 and BG01V},
journal = {BMC Cell Biology},
year = {2009},
volume = {10},
pages = {44},
number = {1},
abstract = {BACKGROUND:A unique and essential property of embryonic stem cells
is the ability to self-renew and differentiate into multiple cell
lineages. However, the possible differences in proliferation and
differentiation capabilities among independently-derived human embryonic
stem cells (hESCs) are not well known because of insufficient characterization.
To address this question, a side-by-side comparison of 1) the ability
to maintain an undifferentiated state and to self-renew under standard
conditions; 2) the ability to spontaneously differentiate into three
primary embryonic germ lineages in differentiating embryoid bodies;
and 3) the responses to directed neural differentiation was made
between three NIH registered hES cell lines I3 (TE03), I6 (TE06)
and BG01V. Lines I3 and I6 possess normal XX and a normal XY karyotype
while BG01V is a variant cell line with an abnormal karyotype derived
from the karyotypically normal cell line BG01.RESULTS:Using immunocytochemistry,
flow cytometry, qRT-PCR and MPSS, we found that all three cell lines
actively proliferated and expressed similar "stemness" markers including
transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4
and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated
into three embryonic germ lineages in embryoid bodies and into neural
cell lineages when cultured in neural differentiation medium. However,
a profound variation in colony morphology, growth rate, BrdU incorporation,
and relative abundance of gene expression in undifferentiated and
differentiated states of the cell lines was observed. Undifferentiated
I3 cells grew significantly slower but their differentiation potential
was greater than I6 and BG01V. Under the same neural differentiation-promoting
conditions, the ability of each cell line to differentiate into neural
progenitors varied.CONCLUSION:Our comparative analysis provides further
evidence for similarities and differences between three hESC lines
in self-renewal, and spontaneous and directed differentiation. These
differences may be associated with inherited variation in the sex,
stage, quality and genetic background of embryos used for hESC line
derivation, and/or changes acquired during passaging in culture.},
doi = {10.1186/1471-2121-10-44},
issn = {1471-2121},
pubmedid = {19500347},
url = {http://www.biomedcentral.com/1471-2121/10/44}
}
@ARTICLE{Taylor2009,
author = {Taylor, Anne M. and Berchtold, Nicole C. and Perreau, Victoria M.
and Tu, Christina H. and Li Jeon, Noo and Cotman, Carl W.},
title = {Axonal mRNA in Uninjured and Regenerating Cortical Mammalian Axons},
journal = {J. Neurosci.},
year = {2009},
volume = {29},
pages = {4697--4707},
number = {15},
month = apr,
abstract = {Using a novel microfluidic chamber that allows the isolation of axons
without contamination by nonaxonal material, we have for the first
time purified mRNA from naive, matured CNS axons, and identified
the presence of >300 mRNA transcripts. We demonstrate that the transcripts
are axonal in nature, and that many of the transcripts present in
uninjured CNS axons overlap with those previously identified in PNS
injury-conditioned DRG axons. The axonal transcripts detected in
matured cortical axons are enriched for protein translational machinery,
transport, cytoskeletal components, and mitochondrial maintenance.
We next investigated how the axonal mRNA pool changes after axotomy,
revealing that numerous gene transcripts related to intracellular
transport, mitochondria and the cytoskeleton show decreased localization
2 d after injury. In contrast, gene transcripts related to axonal
targeting and synaptic function show increased localization in regenerating
cortical axons, suggesting that there is an increased capacity for
axonal outgrowth and targeting, and increased support for synapse
formation and presynaptic function in regenerating CNS axons after
injury. Our data demonstrate that CNS axons contain many mRNA species
of diverse functions, and suggest that, like invertebrate and PNS
axons, CNS axons synthesize proteins locally, maintaining a degree
of autonomy from the cell body.},
url = {http://www.jneurosci.org/cgi/content/abstract/29/15/4697}
}
@ARTICLE{Taylor2011,
author = {Taylor, David and Wilkison, Michelle and Voyich, Jovanka and Meissner,
Nicole},
title = {Prevention of Bone Marrow Cell Apoptosis and Regulation of Hematopoiesis
by Type I IFNs during Systemic Responses to Pneumocystis Lung Infection},
journal = {J. Immunol.},
year = {2011},
volume = {186},
pages = {5956--5967},
number = {10},
month = may,
abstract = {We recently demonstrated that lack of type I IFN signaling (IFNAR
knockout) in lymphocyte-deficient mice (IFrag-/-) results in bone
marrow (BM) failure after Pneumocystis lung infection, whereas lymphocyte-deficient
mice with intact IFNAR (RAG-/-) had normal hematopoiesis. In the
current work, we performed studies to define further the mechanisms
involved in the induction of BM failure in this system. BM chimera
experiments revealed that IFNAR expression was required on BM-derived
but not stroma-derived cells to prevent BM failure. Signals elicited
after day 7 postinfection appeared critical in determining BM cell
fate. We observed caspase-8- and caspase-9-mediated apoptotic cell
death, beginning with neutrophils. Death of myeloid precursors was
associated with secondary oxidative stress, and decreasing colony-forming
activity in BM cell cultures. Treatment with N-acetylcysteine could
slow the progression of, but not prevent, BM failure. Type I IFN
signaling has previously been shown to expand the neutrophil life
span and regulate the expression of some antiapoptotic factors. Quantitative
RT-PCR demonstrated reduced mRNA abundance for the antiapoptotic
factors BCL-2, IAP2, MCL-1, and others in BM cells from IFrag-/-
compared with that in BM cells from RAG-/- mice at day 7. mRNA and
protein for the proapoptotic cytokine TNF- was increased, whereas
mRNA for the growth factors G-CSF and GM-CSF was reduced. In vivo
anti-TNF- treatment improved precursor cell survival and activity
in culture. Thus, we propose that lack of type I IFN signaling results
in decreased resistance to inflammation-induced proapoptotic stressors
and impaired replenishment by precursors after systemic responses
to Pneumocystis lung infection. Our finding may have implications
in understanding mechanisms underlying regenerative BM depression/failure
during complex immune deficiencies such as AIDS.},
comment = {10.4049/jimmunol.1003558},
url = {http://www.jimmunol.org/cgi/content/abstract/186/10/5956}
}
@ARTICLE{Taylor2010,
author = {Taylor, Douglas D. and Gercel-Taylor, Cicek},
title = {Corrigendum to "MicroRNA signatures of tumor-derived exosomes as
diagnostic biomarkers of ovarian cancer" [Gynecologic Oncology 110:
13-21, 2008]},
journal = {Gynecologic Oncology},
year = {2010},
volume = {116},
pages = {153--153},
number = {1},
month = jan,
issn = {0090-8258},
url = {http://www.sciencedirect.com/science/article/B6WG6-4XJN4N4-5/2/8fdf0c15fe0515eca19ad36714018264}
}
@ARTICLE{Taylor2008,
author = {Taylor, Douglas D. and Gercel-Taylor, Cicek},
title = {MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers
of ovarian cancer},
journal = {Gynecologic Oncology},
year = {2008},
volume = {110},
pages = {13--21},
number = {1},
month = jul,
abstract = {Objectives Most ovarian cancer patients are diagnosed at an advanced
stage (67%) and prospects for significant improvement in survival
reside in early diagnosis. While expression patterns of a recently
identified biomarker family, microRNA, appear to be characteristic
of tumor type and developmental origin, microRNA profiling has been
limited to tissue specimens. Tumors actively release exosomes into
the peripheral circulation and we now demonstrate the association
of microRNAs with circulating tumor-derived exosomes.Methods Circulating
tumor exosomes were isolated using a modified MACS procedure with
anti-EpCAM. Initially, microRNA profiles of ovarian tumors were compared
to those of tumor exosomes isolated from the same patients. Levels
of 8 microRNAs (miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203,
miR-205 and miR-214) previously demonstrated as diagnostic, were
compared in exosomes isolated from sera specimens of women with benign
disease and various stages of ovarian cancer.Results MicroRNA from
ovarian tumor cells and exosomes from the same patients were positive
for 218 of 467 mature microRNAs analyzed. The levels of the 8 specific
microRNAs were similar between cellular and exosomal microRNAs (exhibiting
correlations from 0.71 to 0.90). While EpCAM-positive exosomes were
detectable in both patients with benign ovarian disease and ovarian
cancer, exosomal microRNA from ovarian cancer patients exhibited
similar profiles, which were significantly distinct from profiles
observed in benign disease. Exosomal microRNA could not be detected
in normal controls.Conclusions These results suggest that microRNA
profiling of circulating tumor exosomes could potentially be used
as surrogate diagnostic markers for biopsy profiling, extending its
utility to screening asymptomatic populations.},
issn = {0090-8258},
keywords = {MicroRNA, Ovarian cancer, Diagnosis, Screening, Exosomes},
url = {http://www.sciencedirect.com/science/article/B6WG6-4SV7KB6-6/2/4b0a8aa9018f1786ede3a894f95f0dea}
}
@ARTICLE{Taylor2005,
author = {Taylor, Gail and Street, Nathaniel R. and Tricker, Penny J. and Sjödin,
Andreas and Graham, Laura and Skogström, Oskar and Calfapietra,
Carlo and Scarascia-Mugnozza, Giuseppe and Jansson, Stefan},
title = {The transcriptome of Populus in elevated CO2},
journal = {New Phytologist},
year = {2005},
volume = {167},
pages = {143--154},
number = {1},
abstract = {Summary * • The consequences of increasing atmospheric carbon
dioxide for long-term adaptation of forest ecosystems remain uncertain,
with virtually no studies undertaken at the genetic level. A global
analysis using cDNA microarrays was conducted following 6Â yr exposure
of Populus × euramericana (clone I-214) to elevated [CO2] in a
FACE (free-air CO2 enrichment) experiment. * • Gene expression
was sensitive to elevated [CO2] but the response depended on the
developmental age of the leaves, and <Â 50 transcripts differed significantly
between different CO2 environments. For young leaves most differentially
expressed genes were upregulated in elevated [CO2], while in semimature
leaves most were downregulated in elevated [CO2]. * • For transcripts
related only to the small subunit of Rubisco, upregulation in LPI
3 and downregulation in LPI 6 leaves in elevated CO2 was confirmed
by anova. Similar patterns of gene expression for young leaves were
also confirmed independently across year 3 and year 6 microarray
data, and using real-time RT–PCR. * • This study provides the
first clues to the long-term genetic expression changes that may
occur during long-term plant response to elevated CO2.},
issn = {1469-8137},
keywords = {elevated [CO2], FACE (free-air CO2 enrichment), gene expression, leaf
development, microarray, Populus},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2005.01450.x}
}
@ARTICLE{Taylor2007,
author = {Taylor, Milton W. and Tsukahara, Takuma and Brodsky, Leonid and Schaley,
Joel and Sanda, Corneliu and Stephens, Matthew J. and McClintick,
Jeanette N. and Edenberg, Howard J. and Li, Lang and Tavis, John
E. and Howell, Charles and Belle, Steven H. and for the Virahep-C
Study Group},
title = {Changes in Gene Expression during Pegylated Interferon and Ribavirin
Therapy of Chronic Hepatitis C Virus Distinguish Responders from
Nonresponders to Antiviral Therapy},
journal = {J. Virol.},
year = {2007},
volume = {81},
pages = {3391--3401},
number = {7},
month = apr,
abstract = {Treating chronic hepatitis C virus (HCV) infection using pegylated
alpha interferon and ribavirin leads to sustained clearance of virus
and clinical improvement in approximately 50% of patients. Response
rates are lower among patients with genotype 1 than with genotypes
2 and 3 and among African-American (AA) patients compared to Caucasian
(CA) patients. Using DNA microarrays, gene expression was assessed
for a group of 33 African-American and 36 Caucasian American patients
with chronic HCV genotype 1 infection during the first 28 days of
treatment. Results were examined with respect to treatment responses
and to race. Patients showed a response to treatment at the gene
expression level in RNA isolated from peripheral blood mononuclear
cells irrespective of degree of decrease in HCV RNA levels. However,
gene expression responses were relatively blunted in patients with
poor viral response (<1.5 log10-IU/ml decrease at 28 days) compared
to those in patients with a marked (>3.5 log10-IU/ml decrease) or
intermediate (1.5 to 3.5 log10-IU/ml decrease) response. The number
of genes that were up- or down-regulated by pegylated interferon
and ribavirin treatment was fewer in patients with a poor response
than in those with an intermediate or marked viral response. However
AA patients had a stronger interferon response than CA patients in
general. The induced levels of known interferon-stimulated genes
such as the 2'5'-oligoadenylate synthetase, MX1, IRF-7, and toll-like
receptor TLR-7 genes was lower in poor-response patients than in
marked- or intermediate-response patients. Thus, the relative lack
of viral response to interferon therapy of hepatitis C virus infection
is associated with blunted interferon cell signaling. No specific
regulatory gene could be identified as responsible for this global
blunting or the racial differences.},
url = {http://jvi.asm.org/cgi/content/abstract/81/7/3391}
}
@ARTICLE{Taylor2004,
author = {Taylor, Theresa B. and Nambiar, Prashant R. and Raja, Rajiv and Cheung,
Evelyn and Rosenberg, Daniel W. and Anderegg, Birgit},
title = {Microgenomics: Identification of new expression profiles via small
and single-cell sample analyses},
journal = {Cytometry},
year = {2004},
volume = {59A},
pages = {254--261},
number = {2},
abstract = {Abstract 10.1002/cyto.a.20051.abs Background Since the sequencing
of the human genome has been finished, microgenomics has been booming,
employing highly sophisticated, high-throughput platforms. But these
mainly chip-based methods can only generate biologically relevant
data if the samples investigated consist of homogenous cell populations,
in which no unwanted cells of different specificity and/or developmental
stage obscure the results. Methods Different sampling methods have
been routinely applied to overcome the problem presented by heterogeneous
samples, e.g., global surveys, cell cultures, and microdissection.
Various methods of laser-assisted microdissection, employing either
positive or negative selection of tissue areas or even single cells,
are available. Results These laser-assisted microdissection methods
allow for fast and precise procurement of extremely small samples.
Through subsequent application of recently developed methods of linear
mRNA amplification in a pool of isolated total RNA, it has now become
possible to perform complex high-throughput RNA expression profiling
by microdissecting and processing even single-cell samples. Conclusions
Studies using the tools and methods of microgenomics have shed light
on how those new approaches will eventually aid in the development
of a new generation of diagnostics, e.g., leading to new patient-specific
drugs tailored to the requirements assessed by assaying only a few
biopsy cells. © 2004 Wiley-Liss, Inc.},
issn = {1552-4930},
keywords = {microgenomics, laser-assisted microdissection, homogenous samples,
single-cell samples, linear amplication, high-throughput platform},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cyto.a.20051}
}
@ARTICLE{Taylor-Edwards2010,
author = {Taylor-Edwards, C.C. and Burrin, D.G. and Matthews, J.C. and McLeod,
K.R. and Holst, J.J. and Harmon, D.L.},
title = {Expression of mRNA for proglucagon and glucagon-like peptide-2 (GLP-2)
receptor in the ruminant gastrointestinal tract and the influence
of energy intake},
journal = {Domest Anim Endocrinol},
year = {2010},
volume = {39},
pages = {181--193},
number = {3},
month = oct,
abstract = {Glucagon-like peptide-2 (GLP-2) is a potent trophic gut hormone, yet
its function in ruminants is relatively unknown. Experiment 1 was
conducted as a pilot study to establish the presence of GLP-2 in
ruminants and to ascertain whether it was responsive to increased
nutrition, as in non-ruminants. Concentrations of intact GLP-2 in
the blood and gut epithelial mRNA expression of proglucagon (GCG)
and the GLP-2 receptor (GLP2R) were measured in 4 ruminally, duodenally,
and ileally cannulated steers. Steers were fed to meet 0.75 × NEM
for 21 d, and then increased to 1.75 × NEM requirement for another
29 d. Blood samples and ruminal, duodenal, and ileal epithelium biopsies
were collected at low intake (Days −6 and −3), acute high intake
(Days 1 and 3), and chronic high intake (Days 7 and 29) periods.
Experiment 2 investigated the mRNA expression pattern of GCG and
GLP2R in epithelial tissue obtained from the forestomachs (rumen,
omasum, and abomasum) and intestines (duodenum, jejunum, ileum, and
colon) of 18 forage-fed Angus steers (260 kg BW). In Experiments
1 and 2, real-time polymerase chain reaction showed that expression
of GCG and GLP2R mRNA was detectable in forestomach tissues, but
expression was greater (P < 0.001) in small intestinal and colon
tissue. High energy intake tended (P = 0.07) to increase plasma GLP-2
during the acute period and was paralleled by a 78% increase (P =
0.07) in ileal GCG mRNA expression. After this initial adaptation,
duodenal GCG mRNA expression increased (P = 0.08) during the chronic
high intake period. Duodenal GLP2R mRNA expression was not affected
by energy intake, but ileal GLP2R expression was increased after
29 d of high energy intake compared to both the low and acute high
intake periods (P = 0.001 and P = 0.01, respectively). These data
demonstrate that cattle express GCG and GLP2R mRNA primarily in small
intestinal and colon tissues. Increased nutrient intake increases
ileal GCG mRNA and plasma GLP-2, suggesting that GLP-2 may play a
role in the trophic response of the ruminant gastrointestinal tract
to increased feed intake.},
issn = {0739-7240},
keywords = {Gut, Growth, Cattle, Nutrition},
publisher = {Elsevier},
refid = {S0739-7240(10)00052-4},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0739724010000524?showall=true}
}
@ARTICLE{Tayrac2011,
author = {de Tayrac, Marie and Aubry, Marc and Saikali, Stephan and Etcheverry,
Amandine and Surbled, Cyrille and Guenot, Frederique and Galibert,
Marie-Dominique and Hamlat, Abderrahmane and Lesimple, Thierry and
Quillien, Veronique and Menei, Philippe and Mosser, Jean},
title = {A 4-Gene Signature Associated with Clinical Outcome in High-Grade
Gliomas},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {317--327},
number = {2},
month = jan,
abstract = {Purpose: Gene expression studies provide molecular insights improving
the classification of patients with high-grade gliomas. We have developed
a risk estimation strategy based on a combined analysis of gene expression
data to search for robust biomarkers associated with outcome in these
tumors. Experimental Design: We performed a meta-analysis using 3
publicly available malignant gliomas microarray data sets (267 patients)
to define the genes related to both glioma malignancy and patient
outcome. These biomarkers were used to construct a risk-score equation
based on a Cox proportional hazards model on a subset of 144 patients.
External validations were performed on microarray data (59 patients)
and on RT-qPCR data (194 patients). The risk-score model performances
(discrimination and calibration) were evaluated and compared with
that of clinical risk factors, MGMT promoter methylation status,
and IDH1 mutational status. Results: This interstudy cross-validation
approach allowed the identification of a 4-gene signature highly
correlated to survival (CHAF1B, PDLIM4, EDNRB, and HJURP), from which
an optimal survival model was built (P < 0.001 in training and validation
sets). Multivariate analysis showed that the 4-gene risk score was
strongly and independently associated with survival (hazard ratio
= 0.46; 95% CI, 0.26-0.81; P = 0.007). Performance estimations indicated
that this score added beyond standard clinical parameters and beyond
both the MGMT methylation status and the IDH1 mutational status in
terms of discrimination (C statistics, 0.827 versus 0.835; P < 0.001).
Conclusion: The 4-gene signature provides an independent risk score
strongly associated with outcome of patients with high-grade gliomas.
Clin Cancer Res; 17(2); 317-27. (C)2011 AACR.},
comment = {10.1158/1078-0432.CCR-10-1126},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/2/317}
}
@ARTICLE{Tayrac2009,
author = {Tayrac, Marie de and Etcheverry, Amandine and Aubry, Marc and Saïkali,
Stephan and Hamlat, Abderrahmane and Quillien, Veronique and Treut,
André Le and Galibert, Marie-Dominique and Mosser, Jean},
title = {Integrative genome-wide analysis reveals a robust genomic glioblastoma
signature associated with copy number driving changes in gene expression},
journal = {Genes Chromosom. Cancer},
year = {2009},
volume = {48},
pages = {55--68},
number = {1},
abstract = {Abstract 10.1002/gcc.20618.abs Glioblastoma multiforme shows multiple
chromosomal aberrations, the impact of which on gene expression remains
unclear. To investigate this relationship and to identify putative
initiating genomic events, we integrated a paired copy number and
gene expression survey in glioblastoma using whole human genome arrays.
Loci of recurrent copy number alterations were combined with gene
expression profiles obtained on the same tumor samples. We identified
a set of 406 “cis-acting DNA targeted genes� corresponding to
genomic aberrations with direct copy-number-driving changes in gene
expression, defined as genes with either significantly concordant
or correlated changes in DNA copy number and expression. Functional
annotation revealed that these genes participate in key processes
of cancer cell biology, providing insights into the genetic mechanisms
driving glioblastoma. The robustness of the gene selection was validated
on an external microarray data set including 81 glioblastomas and
23 non-neoplastic brain samples. The integration of array CGH and
gene expression data highlights a robust cis-acting DNA targeted
genes signature that may be critical for glioblastoma progression,
with two tumor suppressor genes PCDH9 and STARD13 that could be involved
in tumor invasiveness and resistance to etoposide. © 2008 Wiley-Liss,
Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20618}
}
@ARTICLE{Tazreiter2008,
author = {Tazreiter, Margit and Leitsch, David and Hatzenbichler, Evelyn and
Mair-Scorpio, Georg E. and Steinborn, Ralf and Schreiber, Martin
and Duchêne, Michael},
title = {Entamoeba histolytica: Response of the parasite to metronidazole
challenge on the levels of mRNA and protein expression},
journal = {Experimental Parasitology},
year = {2008},
volume = {120},
pages = {403--410},
number = {4},
month = dec,
abstract = {Entamoeba histolytica remains a cause of significant morbidity and
mortality in many countries. Although metronidazole has been used
for the treatment of amoebiasis for several decades, little is known
on how the amoebae react to this challenge on the levels of mRNA
and protein expression. In this study, we examined their response
using a focused microarray, quantitative RT-PCR, and two-dimensional
gel electrophoresis (2DE). The amoebae modestly increased the levels
of mRNA coding for superoxide dismutase, peroxiredoxin, ferredoxin,
thioredoxin reductase, and the galactose/N-acetylgalactosamine specific
lectin light and heavy chains. The mRNAs encoding actin and the 70 kDa
and 101 kDa heat shock proteins were decreased. All the changes occured
within 1 h of exposition, with very little further changes. In addition,
the proteome revealed only very few changes. Taken together, E. histolytica
appears to make only modest mRNA and protein expression changes when
confronted with an unknown chemical stress.},
issn = {0014-4894},
keywords = {Entamoeba histolytica, Metronidazole, Microarray, Proteomics, 2DE,
two-dimensional electrophoresis, EC number, enzyme commission number,
DTT, dithiothreitol, IPG, immobilized pH gradient, PFOR, pyruvate
ferredoxin oxidoreductase, qRT-PCR, quantitative real-time reverse
transcription polymerase chain reaction, REST, Relative Expression
Software Tool, RIN, RNA integrity number},
url = {http://www.sciencedirect.com/science/article/B6WFH-4TJ1HPC-4/2/b3fecee66ad46871853773aeba540dac}
}
@ARTICLE{Taibi2011,
author = {Taïbi, Amel and Dabour, Nassra and Lamoureux, Maryse and Roy, Denis
and LaPointe, Gisèle},
title = {Comparative transcriptome analysis of Lactococcus lactis subsp. cremoris
strains under conditions simulating Cheddar cheese manufacture},
journal = {International Journal of Food Microbiology},
year = {2011},
volume = {146},
pages = {263--275},
number = {3},
month = apr,
abstract = {Gene expression in response to technological variations can influence
fermentation and flavor generation in Cheddar cheese, and can vary
from one lactococcal strain to another, perceived as differences
in starter performance. The aim of this study was to determine the
influence of cheese cooking temperature at 38 °C and salting on the
transcriptional profiles of four closely related strains of L. lactis
subsp. cremoris under simulated conditions of Cheddar cheese manufacture.
Two responses could be distinguished, a core gene expression, corresponding
to the common response of all strains and strain-specific response
during the Cheddar simulating process. For the core gene expression
after heating of inoculated milk at 38 °C, two groups of differentially
expressed genes were identified: i) stress response and ii) carbohydrate
and amino acid metabolism. The response to combined stresses of heat,
acid and salt resulted in: i) general decrease of functions linked
to cell division and metabolism, ii) specific responses related to
stress such as the induction of genes coding for chaperones and proteases
and iii) expression of prophage lytic systems for certain strains.
Strain-specific responses were mainly observed in three of the four
tested strains. These responses were the induction of genes related
to osmotic stress or the release of CodY repression leading to the
activation of oligopeptide transporters as well as the bcaT gene,
related to amino acid degradation for the production of flavor. Comparing
transcriptomes provides a core expression profile that contributes
to understanding gene expression responses to environmental variations.
The strain-specific responses identify predictive markers for the
transcriptional state of starter strains before they enter the cheese
ripening phase.},
issn = {0168-1605},
keywords = {Lactococcus lactis subsp. cremoris, Cheese, Comparative transcriptome
hybridization, Core transcriptome, RT-qPCR},
url = {http://www.sciencedirect.com/science/article/pii/S0168160511001140}
}
@ARTICLE{Tchaparian2011,
author = {Tchaparian, Eskouhie H. and Houghton, Jessica S. and Uyeda, Craig
and Grillo, Mark P. and Jin, Lixia},
title = {Effect of Culture Time on the Basal Expression Levels of Drug Transporters
in Sandwich-Cultured Primary Rat Hepatocytes},
journal = {Drug Metab. Dispos.},
year = {2011},
volume = {39},
pages = {2387-2394},
number = {12},
abstract = {Sandwich-cultured rat hepatocytes are used in drug discovery for pharmacological
and toxicological assessment of drug candidates, yet their utility
as a functional model for drug transporters has not been fully characterized.
To evaluate the system as an in vitro model for drug transport, expression
changes of hepatic transporters relative to whole liver and freshly
isolated hepatocytes (day 0) were examined by real-time quantitative
reverse transcription-polymerase chain reaction for 4 consecutive
days of culture. No significant differences in transporter expression
levels were observed between freshly isolated hepatocytes and whole
liver. Two distinct mRNA profiles were detected over time showing
1) a more than 5-fold decline in levels of uptake transporters such
as Na+-taurocholate cotransporting polypeptide (Ntcp), organic anion
transporter (Oat) 2, organic anion-transporting polypeptide (Oatp)
1a1, Oatp1a4, and Oatp1b2 and 2) a greater than 5-fold increase of
efflux transporters P-glycoprotein (P-gp), breast cancer resistance
protein (Bcrp), and multidrug resistance-related proteins (Mrp) 1,
2, 3, and 4. In addition, protein levels and functional activities
for selected transporters were also determined. Protein levels for
Mrp2, Bcrp, P-gp, Ntcp, and Oatp1a4 corresponded to changes in mRNA.
Functional activities of Oatps and Oct1 exhibited a 3- and 4-fold
decrease on day 2 and day 4, respectively, relative to that on day
0, whereas a more than 10-fold reduction in Oat2 activity was observed.
These results indicate that the cell culture conditions used herein
did not provide an optimal environment for expression of all hepatic
transporters. Significant time-dependent alterations in basal gene
expression patterns of transporters were detected compared with those
in liver or freshly isolated hepatocytes. Further work and new strategies
are required to improve the validity of this model as an in vitro
tool for in vivo drug transport or biliary clearance prediction.},
doi = {10.1124/dmd.111.039545},
eprint = {http://dmd.aspetjournals.org/cgi/reprint/39/12/2387.pdf},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/39/12/2387}
}
@ARTICLE{Tchatalbachev2010,
author = {Tchatalbachev, Svetlin and Ghai, Rohit and Hossain, Hamid and Chakraborty,
Trinad},
title = {Gram-positive pathogen bacteria induce a common early response in
human monocytes},
journal = {BMC Microbiology},
year = {2010},
volume = {10},
pages = {275},
number = {1},
abstract = {BACKGROUND:We infected freshly isolated human peripheral monocytes
with live bacteria of three clinically important gram-positive bacterial
species, Staphylococcus aureus, Streptococcus pneumoniae and Listeria
monocytogenes and studied the ensuing early transcriptional response
using expression microarrays. Thus the observed response was unbiased
by signals originating from other helper and effector cells of the
host and was not limited to induction by solitary bacterial constituents.
Results: Activation of monocytes was demonstrated by the upregulation
of chemokine rather than interleukin genes except for the prominent
expression of interleukin 23, marking it as the early lead cytokine.
This activation was accompanied by cytoskeleton rearrangement signals
and a general anti-oxidative stress and anti-apoptotic reaction.
Remarkably, the expression profiles also provide evidence that monocytes
participate in the regulation of angiogenesis and endothelial function
in response to these pathogens. Conclusion: Regardless of the invasion
properties and survival mechanisms of the pathogens used, we found
that the early response comprised of a consistent and common response.
The common response was hallmarked by the upregulation of interleukin
23, a rather unexpected finding regarding Listeria infection, as
this cytokine has been linked primarily to the control of extracellular
bacterial dissemination.},
doi = {10.1186/1471-2180-10-275},
issn = {1471-2180},
pubmedid = {21044323},
url = {http://www.biomedcentral.com/1471-2180/10/275}
}
@ARTICLE{Tchernitsa2010,
author = {Tchernitsa, Oleg and Kasajima, Atsuko and Schäfer, Reinhold and
Kuban, Ralf-Jürgen and Ungethüm, Ute and Györffy, Balazs and Neumann,
Ulf and Simon, Eva and Weichert, Wilko and Ebert, Matthias PA and
Röcken, Christoph},
title = {Systematic evaluation of the miRNA-ome and its downstream effects
on mRNA expression identifies gastric cancer progression},
journal = {J. Pathol.},
year = {2010},
volume = {222},
pages = {310--319},
number = {3},
abstract = {Abstract We investigated the differential expression of Dicer and
Drosha, as well as that of microRNA (miRNA), in adjacent normal and
tumour samples of patients with gastric cancer. The expression of
Dicer and Drosha was studied by immunohistochemistry in 332 gastric
cancers and correlated with clinico-pathological patient characteristics.
Differential expression of miRNAs was studied using the Invitrogen
NCodeâ„¢ Multi-Species miRNA Microarray Probe Set containing 857
mammalian probes in a test set of six primary gastric cancers (three
with and three without lymph node metastases). Differential expression
was validated by RT-PCR on an independent validation set of 20 patients
with gastric cancer. Dicer and Drosha were differentially expressed
in non-neoplastic and neoplastic gastric tissue. The expression of
Drosha correlated with local tumour growth and was a significant
independent prognosticator of patient survival. Twenty miRNAs were
up- and two down-regulated in gastric carcinoma compared with non-neoplastic
tissue. Six of these miRNAs separated node-positive from node-negative
gastric cancers, ie miR-103, miR-21, miR-145, miR-106b, miR-146a,
and miR-148a. Five miRNAs expressed differentially in node-positive
cancers had conserved binding sites for mRNAs differentially expressed
in the same set of tumour samples. Gastric cancer shows a complex
derangement of the miRNA-ome, including Dicer and Drosha. These changes
correlate independently with patient prognosis and probably influence
local tumour growth and nodal spread. Copyright © 2010 Pathological
Society of Great Britain and Ireland. Published by John Wiley & Sons,
Ltd.},
issn = {1096-9896},
keywords = {gastric cancer, lymph node metastases, miRNA, prognosis, Dicer, Drosha},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2759}
}
@ARTICLE{Tchoghandjian2009,
author = {Tchoghandjian, Aurelie and Fernandez, Carla and Colin, Carole and
El Ayachi, Ikbale and Voutsinos-Porche, Brigitte and Fina, Frederic
and Scavarda, Didier and Piercecchi-Marti, Marie-Dominique and Intagliata,
Dominique and Ouafik, L'Houcine and Fraslon-Vanhulle, Caroline and
Figarella-Branger, Dominique},
title = {Pilocytic astrocytoma of the optic pathway: a tumour deriving from
radial glia cells with a specific gene signature},
journal = {Brain},
year = {2009},
volume = {132},
pages = {1523--1535},
number = {6},
month = jun,
abstract = {Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly
in childhood. They share features of both astroglial and oligodendroglial
lineages. These tumours affect preferentially the cerebellum (benign
clinical course) and the optic pathway, especially the hypothalamo-chiasmatic
region (poor prognosis). Understanding the molecular basis responsible
for the aggressive behaviour of hypothalamo-chiasmatic pilocytic
astrocytomas is a prerequisite to setting up new molecular targeted
therapies. We used the microarray technique to compare the transcriptional
profiles of five hypothalamo-chiasmatic and six cerebellar pilocytic
astrocytomas. Validation of the microarray results and comparison
of the tumours with normal developing tissue was done by quantitative
real-time PCR and immunohistochemistry. Results demonstrate that
cerebellar and hypothalamo-chiasmatic pilocytic astrocytomas are
two genetically distinct and topography-dependent entities. Numerous
genes upregulated in hypothalamo-chiasmatic pilocytic astrocytomas
also increased in the developing chiasm, suggesting that developmental
genes mirror the cell of origin whereas migrative, adhesive and proliferative
genes reflect infiltrative properties of these tumours. Of particular
interest, NOTCH2, a gene expressed in radial glia and involved in
gliomagenesis, was upregulated in hypothalamo-chiasmatic pilocytic
astrocytomas. In order to find progenitor cells that could give rise
to hypothalamo-chiasmatic pilocytic astrocytomas, we performed a
morphological study of the hypothalamo-chiasmatic region and identified,
in the floor of the third ventricle, a unique population of vimentin-
and glial fibrillary acidic protein-positive cells highly suggestive
of radial glia cells. Therefore, pilocytic astrocytomas of the hypothalamo-chiasmatic
region should be considered as a distinct entity which probably originates
from a unique population of cells with radial glia phenotype.},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/132/6/1523}
}
@ARTICLE{Teaster2007,
author = {Teaster, Neal D. and Motes, Christy M. and Tang, Yuhong and Wiant,
William C. and Cotter, Matthew Q. and Wang, Yuh-Shuh and Kilaru,
Aruna and Venables, Barney J. and Hasenstein, Karl H. and Gonzalez,
Gabriel and Blancaflor, Elison B. and Chapman, Kent D.},
title = {N-Acylethanolamine Metabolism Interacts with Abscisic Acid Signaling
in Arabidopsis thaliana Seedlings},
journal = {PLANT CELL},
year = {2007},
volume = {19},
pages = {2454--2469},
number = {8},
month = aug,
abstract = {N-Acylethanolamines (NAEs) are bioactive acylamides that are present
in a wide range of organisms. In plants, NAEs are generally elevated
in desiccated seeds, suggesting that they may play a role in seed
physiology. NAE and abscisic acid (ABA) levels were depleted during
seed germination, and both metabolites inhibited the growth of Arabidopsis
thaliana seedlings within a similar developmental window. Combined
application of low levels of ABA and NAE produced a more dramatic
reduction in germination and growth than either compound alone. Transcript
profiling and gene expression studies in NAE-treated seedlings revealed
elevated transcripts for a number of ABA-responsive genes and genes
typically enriched in desiccated seeds. The levels of ABI3 transcripts
were inversely associated with NAE-modulated growth. Overexpression
of the Arabidopsis NAE degrading enzyme fatty acid amide hydrolase
resulted in seedlings that were hypersensitive to ABA, whereas the
ABA-insensitive mutants, abi1-1, abi2-1, and abi3-1, exhibited reduced
sensitivity to NAE. Collectively, our data indicate that an intact
ABA signaling pathway is required for NAE action and that NAE may
intersect the ABA pathway downstream from ABA. We propose that NAE
metabolism interacts with ABA in the negative regulation of seedling
development and that normal seedling establishment depends on the
reduction of the endogenous levels of both metabolites.},
url = {http://www.plantcell.org/cgi/content/abstract/19/8/2454}
}
@ARTICLE{Tebbji2010,
author = {Tebbji, Faiza and Nantel, André and Matton, Daniel},
title = {Transcription profiling of fertilization and early seed development
events in a solanaceous species using a 7.7 K cDNA microarray from
Solanum chacoense ovules},
journal = {BMC Plant Biology},
year = {2010},
volume = {10},
pages = {174},
number = {1},
abstract = {BACKGROUND:To provide a broad analysis of gene expression changes
in developing embryos from a solanaceous species, we produced amplicon-derived
microarrays with 7741 ESTs isolated from Solanum chacoense ovules
bearing embryos from all developmental stages. Our aims were to:
1) identify genes expressed in a tissue-specific and temporal-specific
manner; 2) define clusters of genes showing similar patterns of spatial
and temporal expression; and 3) identify stage-specific or transition-specific
candidate genes for further functional genomic analyses.RESULTS:We
analyzed gene expression during S. chacoense embryogenesis in a series
of experiments with probes derived from ovules isolated before and
after fertilization (from 0 to 22 days after pollination), and from
leaves, anthers, and styles. From the 6374 unigenes present in our
array, 1024 genes were differentially expressed (= ± 2 fold change,
p value = 0.01) in fertilized ovules compared to unfertilized ovules
and only limited expression overlap was observed between these genes
and the genes expressed in the other tissues tested, with the vast
majority of the fertilization-regulated genes specifically or predominantly
expressed in ovules (955 genes). During embryogenesis three major
expression profiles corresponding to early, middle and late stages
of embryo development were identified. From the early and middle
stages, a large number of genes corresponding to cell cycle, DNA
processing, signal transduction, and transcriptional regulation were
found. Defense and stress response-related genes were found in all
stages of embryo development. Protein biosynthesis genes, genes coding
for ribosomal proteins and other components of the translation machinery
were highly expressed in embryos during the early stage. Genes for
protein degradation were overrepresented later in the middle and
late stages of embryo development. As expected, storage protein transcripts
accumulated predominantly in the late stage of embryo development.CONCLUSION:Our
analysis provides the first study in a solanaceous species of the
transcriptional program that takes place during the early phases
of plant reproductive development, including all embryogenesis steps
during a comprehensive time-course. Our comparative expression profiling
strategy between fertilized and unfertilized ovules identified a
subset of genes specifically or predominantly expressed in ovules
while a closer analysis between each consecutive time point allowed
the identification of a subset of stage-specific and transition-specific
genes.},
doi = {10.1186/1471-2229-10-174},
issn = {1471-2229},
pubmedid = {20704744},
url = {http://www.biomedcentral.com/1471-2229/10/174}
}
@ARTICLE{Tedeschi2011,
author = {P. Tedeschi and J.D. Coïsson and A. Maietti and E. Cereti and C.
Stagno and F. Travaglia and M. Arlorio and V. Brandolini},
title = {Chemotype and genotype combined analysis applied to tomato (Lycopersicon
esculentum Mill.) analytical traceability},
journal = {Journal of Food Composition and Analysis},
year = {2011},
volume = {24},
pages = {131 - 139},
number = {2},
abstract = {A large number of fresh fruits and vegetables are primary sources
of antioxidants; tomato (Lycopersicon esculentum Mill.) is accepted
worldwide as a significant source of antioxidant functional compounds
(vitamin C, lycopene, rutin). Many cultivars and hybrids of tomato,
having different chemical and nutritional characteristics, are available
on the market. Tomato cultivars for industrial processing are very
different, not only in fruit characteristics (size, shape), but also
in lycopene and antioxidant contents. The aim of this study was the
chemotyping and genotyping of the tomato varieties Heinz 3402, Leader
and Perfectpeel, (1) to evaluate the genetic traceability of these
varieties, and (2) to determine whether their functional antioxidants
compounds are useful markers of traceability. Principal component
analysis (PCA) was first applied to the Random Polymorphic DNA (RAPD)
fingerprints, confirming that this approach is a powerful identification
method at intra-specific level. Heinz 3402 showed the highest antioxidant
activity, followed by Perfectpeel and Leader varieties. Perfectpeel
showed the lower lycopene content, while Leader and Heinz 3402 showed
significantly higher values (13.68 and 15.78 mg/100 g,
fresh weight, respectively). The highest rutin content was observed
in Heinz 3402 (12.46 ± 0.69, mg/100 g, fresh weight),
followed by Leader (7.87 ± 0.72) and Perfectpeel (2.70 ± 0.68).
Antioxidant capacity was significantly correlated with the lycopene
and rutin content. Finally, PCA was applied to chemotype data-sets,
confirming both mineral content and functional antioxidant compounds
as useful markers to unambiguously identify these high-lycopene content
varieties.},
doi = {10.1016/j.jfca.2010.06.008},
issn = {0889-1575},
keywords = {Tomato (Lycopersicon esculentum
Mill.)},
url = {http://www.sciencedirect.com/science/article/pii/S0889157510002681}
}
@ARTICLE{Teekakirikul2011,
author = {Teekakirikul, Polakit and Cox, Stephanie and Funke, Birgit and Rehm,
Heidi L.},
title = {Targeted Sequencing Using Affymetrix CustomSeq Arrays},
journal = {Current Protocols in Human Genetics},
year = {2011},
abstract = {This unit provides a basic protocol for oligo hybridization-based
sequencing technology and resulting data analysis specific to the
Affymetrix GeneChip CustomSeq Resequencing Array platform. All steps
and critical aspects related to array design, experimental protocols,
data management, and base-calling algorithms are addressed. This
unit is particularly appropriate for sequencing targeted regions
of the genome of up to 300 kilobases. The basic technology is most
suitable for detecting substitution mutations, unless targeted indel
probes are added. Curr. Protoc. Hum. Genet. 69:7.18.1-7.18.17 ©
2011 by John Wiley & Sons, Inc.},
booktitle = {Current Protocols in Human Genetics},
doi = {10.1002/0471142905.hg0718s69},
isbn = {9780471142904},
keywords = {resequencing microarrays, CustomSeq, base-calling, sequence-specific,
hybridization, mutation detection},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/0471142905.hg0718s69}
}
@INBOOK{Teekakirikul2001,
title = {Targeted Sequencing Using Affymetrix CustomSeq Arrays},
publisher = {John Wiley \& Sons, Inc.},
year = {2001},
author = {Teekakirikul, Polakit and Cox, Stephanie and Funke, Birgit and Rehm,
Heidi L.},
abstract = {This unit provides a basic protocol for oligo hybridization-based
sequencing technology and resulting data analysis specific to the
Affymetrix GeneChip CustomSeq Resequencing Array platform. All steps
and critical aspects related to array design, experimental protocols,
data management, and base-calling algorithms are addressed. This
unit is particularly appropriate for sequencing targeted regions
of the genome of up to 300 kilobases. The basic technology is most
suitable for detecting substitution mutations, unless targeted indel
probes are added. Curr. Protoc. Hum. Genet. 69:7.18.1-7.18.17 ©
2011 by John Wiley & Sons, Inc.},
booktitle = {Current Protocols in Human Genetics},
doi = {10.1002/0471142905.hg0718s69},
isbn = {9780471142904},
keywords = {resequencing microarrays, CustomSeq, base-calling, sequence-specific,
hybridization, mutation detection},
url = {http://dx.doi.org/10.1002/0471142905.hg0718s69}
}
@ARTICLE{Teer2010,
author = {Teer, Jamie K. and Bonnycastle, Lori L. and Chines, Peter S. and
Hansen, Nancy F. and Aoyama, Natsuyo and Swift, Amy J. and Abaan,
Hatice Ozel and Albert, Thomas J. and NISC Comparative Sequencing
Program and Margulies, Elliott H. and Green, Eric D. and Collins,
Francis S. and Mullikin, James C. and Biesecker, Leslie G.},
title = {Systematic comparison of three genomic enrichment methods for massively
parallel DNA sequencing},
journal = {Genome Res.},
year = {2010},
volume = {20},
pages = {1420--1431},
number = {10},
month = oct,
abstract = {Massively parallel DNA sequencing technologies have greatly increased
our ability to generate large amounts of sequencing data at a rapid
pace. Several methods have been developed to enrich for genomic regions
of interest for targeted sequencing. We have compared three of these
methods: Molecular Inversion Probes (MIP), Solution Hybrid Selection
(SHS), and Microarray-based Genomic Selection (MGS). Using HapMap
DNA samples, we compared each of these methods with respect to their
ability to capture an identical set of exons and evolutionarily conserved
regions associated with 528 genes (2.61 Mb). For sequence analysis,
we developed and used a novel Bayesian genotype-assigning algorithm,
Most Probable Genotype (MPG). All three capture methods were effective,
but sensitivities (percentage of targeted bases associated with high-quality
genotypes) varied for an equivalent amount of pass-filtered sequence:
for example, 70% (MIP), 84% (SHS), and 91% (MGS) for 400 Mb. In contrast,
all methods yielded similar accuracies of >99.84% when compared to
Infinium 1M SNP BeadChip-derived genotypes and >99.998% when compared
to 30-fold coverage whole-genome shotgun sequencing data. We also
observed a low false-positive rate with all three methods; of the
heterozygous positions identified by each of the capture methods,
>99.57% agreed with 1M SNP BeadChip, and >98.840% agreed with the
whole-genome shotgun data. In addition, we successfully piloted the
genomic enrichment of a set of 12 pooled samples via the MGS method
using molecular bar codes. We find that these three genomic enrichment
methods are highly accurate and practical, with sensitivities comparable
to that of 30-fold coverage whole-genome shotgun data.},
url = {http://genome.cshlp.org/cgi/content/abstract/20/10/1420}
}
@ARTICLE{Tefferi2004,
author = {Tefferi, Ayalew and Lasho, Terra L. and Wolanskyj, Alexandra P. and
Mesa, Ruben A.},
title = {Neutrophil PRV-1 expression across the chronic myeloproliferative
disorders and in secondary or spurious polycythemia},
journal = {Blood},
year = {2004},
volume = {103},
pages = {3547--3548},
number = {9},
month = may,
abstract = {Recent studies have demonstrated neutrophil overexpression of the
polycythemia rubra vera-1 (PRV-1) gene in polycythemia vera (PV)
but not in secondary or spurious polycythemia (SP). To validate as
well as expand upon this novel observation, we conducted a prospective
study of 88 subjects: 30 with PV, 22 with SP, 14 with essential thrombocythemia
(ET), 12 with myelofibrosis with myeloid metaplasia (MMM), and 10
controls. To minimize interstudy methodologic differences, we used
a published real-time polymerase chain reaction (PCR)-based assay.
The proportion of patients with increased neutrophil PRV-1 expression
was 83% in PV, 21% in ET, 42% in MMM, 18% in SP, and 0% in controls.
All 5 MMM patients with PRV-1 up-regulation had an antecedent history
of PV. We conclude that neutrophil PRV-1 up-regulation is a characteristic
feature of PV that may not be affected by fibrotic transformation.
However, quantifying neutrophil PRV-1 mRNA, while complementary to
other tests, is not in itself sufficient for the diagnosis of PV.
(Blood. 2004;103:3547-3548)},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/103/9/3547}
}
@ARTICLE{Tegel2010,
author = {Tegel, Hanna and Tourle, Samuel and Ottosson, Jenny and Persson,
Anja},
title = {Increased levels of recombinant human proteins with the Escherichia
coli strain Rosetta(DE3)},
journal = {Protein Expression and Purification},
year = {2010},
volume = {69},
pages = {159--167},
number = {2},
month = feb,
abstract = {The effect of two Escherichia coli expression strains on the production
of recombinant human protein fragments was evaluated. High-throughput
protein production projects, such as the Swedish Human Protein Atlas
project, are dependent on high protein yield and purity. By changing
strain from E. coli BL21(DE3) to E. coli Rosetta(DE3) the overall
success rate of the protein production has increased dramatically.
The Rosetta(DE3) strain compensates for a number of rare codons.
Here, we describe how the protein expression of human gene fragments
in E. coli strains BL21(DE3) and Rosetta(DE3) was evaluated in two
stages. Initially a test set of 68 recombinant proteins that previously
had been expressed in BL21(DE3) was retransformed and expressed in
Rosetta(DE3). The test set generated very positive results with an
improved expression yield and a significantly better purity of the
protein product which prompted us to implement the Rosetta(DE3) strain
in the high-throughput protein production. Except for analysis of
protein yield and purity the sequences were also analyzed regarding
number of rare codons and rare codon clusters. The content of rare
codons showed to have a significant effect on the protein purity.
Based on the results of this study the atlas project permanently
changed expression strain to Rosetta(DE3).},
issn = {1046-5928},
keywords = {E. coli, BL21(DE3), Rosetta(DE3), Expression strain, Protein production,
High-throughput},
url = {http://www.sciencedirect.com/science/article/B6WPJ-4X54JR3-1/2/37f7de82019a59e53eb60ca78182cf2c}
}
@ARTICLE{Teixeira2011,
author = {Teixeira, Cristina C. and Xiang, Jenny and Roy, Rani and Kudrashov,
Valery and Binderman, Itzhak and Mayer-Kuckuk, Philipp and Boskey,
Adele L.},
title = {Changes in matrix protein gene expression associated with mineralization
in the differentiating chick limb-bud micromass culture system},
journal = {Journal of Cellular Biochemistry},
year = {2011},
volume = {112},
pages = {607--613},
number = {2},
abstract = {Abstract Chick limb-bud mesenchymal stem cells plated in high density
culture in the presence of 4 mM inorganic phosphate and vitamin
C differentiate and form a mineralizable matrix, resembling that
of the chick growth plate. To further elucidate the mechanism that
allows these cultures to form physiologic hydroxyapatite deposits,
and how the process can be manipulated to gain insight into mineralization
mechanisms, we compared gene expression in mineralizing (with 4 mM
inorganic phosphate) and non-mineralizing cultures (containing only
1 mM inorganic phosphate) at the start of mineralization (day 11)
and after mineralization reached a plateau (day 17) using a chick
specific microarray. Based on replicate microarray experiments and
K-cluster analysis, several genes associated with the mineralization
process were identified, and their expression patterns confirmed
throughout the culture period by quantitative RT-PCR. The functions
of bone morphogenetic protein 1, BMP1, dentin matrix protein 1, DMP1,
the sodium phosphate co-transporter, NaPi IIb, matrix metalloprotease
13. MMP-13, and alkaline phosphatase, along with matrix protein genes
(type X collagen, bone sialoprotein, and osteopontin) usually associated
with initiation of mineralization are discussed. J. Cell. Biochem.
112: 607–613, 2011. © 2010 Wiley-Liss, Inc.},
doi = {10.1002/jcb.22951},
issn = {1097-4644},
keywords = {chick limb-bud, micromass culture, mineralization, microarray, gene
expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.22951}
}
@ARTICLE{Teixeira2006,
author = {Teixeira, Miguel Cacho and Fernandes, Alexandra Ramos and Mira, Nuno
Pereira and Becker, Jörg Dieter and Sá-Correia, Isabel},
title = {Early transcriptional response of Saccharomyces cerevisiae to stress
imposed by the herbicide 2,4-dichlorophenoxyacetic acid},
journal = {FEMS Yeast Research},
year = {2006},
volume = {6},
pages = {230--248},
number = {2},
abstract = {Abstract The global gene transcription pattern of the eukaryotic experimental
model Saccharomyces cerevisiae in response to sudden aggression with
the widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)
was analysed. Under acute stress, 14% of the yeast transcripts suffered
a greater than twofold change. The yeastract database was used to
predict the transcription factors mediating the response registered
in this microarray analysis. Most of the up-regulated genes in response
to 2,4-D are known targets of Msn2p, Msn4p, Yap1p, Pdr1p, Pdr3p,
Stp1p, Stp2p and Rpn4p. The major regulator of ribosomal protein
genes, Sfp1p, is known to control 60% of the down-regulated genes,
in particular many involved in the transcriptional and translational
machinery and in cell division. The yeast response to the herbicide
includes the increased expression of genes involved in the oxidative
stress response, the recovery or degradation of damaged proteins,
cell wall remodelling and multiple drug resistance. Although the
protective role of TPO1 and PDR5 genes was confirmed, the majority
of the responsive genes encoding multidrug resistance do not confer
resistance to 2,4-D. The increased expression of genes involved in
alternative carbon and nitrogen source metabolism, fatty acid β-oxidation
and autophagy was also registered, suggesting that acute herbicide
stress leads to nutrient limitation.},
issn = {1567-1364},
keywords = {yeast, 2,4-D, microarrays, oxidative stress, nutrient limitation,
multidrug resistance transporters, response to chemical stress, environmental
toxicology},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1567-1364.2006.00041.x}
}
@ARTICLE{Teles2011,
author = {Teles, M. and Mackenzie, S. and Boltaña, S. and Callol, A. and Tort,
L.},
title = {Gene expression and TNF-alpha secretion profile in rainbow trout
macrophages following exposures to copper and bacterial lipopolysaccharide},
journal = {Fish \& Shellfish Immunology},
year = {2011},
volume = {30},
pages = {340--346},
number = {1},
month = jan,
abstract = {Fish macrophage function can be altered after exposure to pathogens
as well as to xenobiotics. Considering that wild and farmed fish
can be exposed in their habitats simultaneously to different types
of stressors, including chemical contaminants (e.g. heavy metals)
and pathogens (e.g. bacteria), it is fundamental to study their impact
either isolated or in combination. Therefore, the present study aimed
to evaluate the effects of copper and bacterial lipopolysaccharide
(LPS), alone and in combination, on the transcription of target genes
related with immune system, respiratory burst activity and cell death,
using rainbow trout macrophages as in vitro model. A cell viability
experiment was performed to determine the sub-lethal concentrations
of copper for rainbow trout macrophages and the LC50-24 h was estimated
at 60 [mu]M. The expression of proinflammatory cytokines, such as
interleukin-1[beta] (IL-1[beta]), interleukin-6 (IL-6) and tumour
necrosis factor-[alpha] (TNF[alpha]) increased after copper and copper
plus LPS exposure. Copper and LPS interact positively inducing an
increase in cytokine expression, which may be indicative of an increased
inflammatory response. However, the increase in TNF[alpha] mRNA expression
induced by 50 [mu]M copper was not accompanied by protein secretion
indicating that mRNA abundance does not always reflect the level
of protein and that the translation of the TNF[alpha] mRNA is somehow
inhibited. Serum amyloid A (SAA) and trout C-polysaccharide binding
protein (TCPBP) mRNA expression also increased after copper, LPS
or LPS plus copper exposure, indicating a role of acute phase proteins
in the local response to inflammation. NADPH oxidase and glutathione
peroxidase gene expression increased in macrophages after 24 h exposure
to copper, LPS or LPS plus copper. The results from the present study
improve the understanding of mechanisms involved in copper toxicity,
as well as the interaction with a simulated-inflammatory process.},
issn = {1050-4648},
keywords = {Rainbow trout, Macrophages, Lipopolysaccharide, Copper, Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S1050464810003487}
}
@ARTICLE{Telias2011,
author = {Telias, Adriana and White, James and Pahl, Donna and Ottesen, Andrea
and Walsh, Christopher},
title = {Bacterial community diversity and variation in spray water sources
and the tomato fruit surface},
journal = {BMC Microbiology},
year = {2011},
volume = {11},
pages = {81},
number = {1},
abstract = {BACKGROUND:Tomato (Solanum lycopersicum) consumption has been one
of the most common causes of produce-associated salmonellosis in
the United States. Contamination may originate from animal waste,
insects, soil or water. Current guidelines for fresh tomato production
recommend the use of potable water for applications coming in direct
contact with the fruit, but due to high demand, water from other
sources is frequently used. We sought to describe the overall bacterial
diversity on the surface of tomato fruit and the effect of two different
water sources (ground and surface water) when used for direct crop
applications by generating a 454-pyrosequencing 16S rRNA dataset
of these different environments. This study represents the first
in depth characterization of bacterial communities in the tomato
fruit surface and the water sources commonly used in commercial vegetable
production.RESULTS:The two water sources tested had a significantly
different bacterial composition. Proteobacteria was predominant in
groundwater samples, whereas in the significantly more diverse surface
water, abundant phyla also included Firmicutes, Actinobacteria and
Verrucomicrobia. The fruit surface bacterial communities on tomatoes
sprayed with both water sources could not be differentiated using
various statistical methods. Both fruit surface environments had
a high representation of Gammaproteobacteria, and within this class
the genera Pantoea and Enterobacter were the most abundant.CONCLUSIONS:Despite
the major differences observed in the bacterial composition of ground
and surface water, the season long use of these very different water
sources did not have a significant impact on the bacterial composition
of the tomato fruit surface. This study has provided the first next-generation
sequencing database describing the bacterial communities living in
the fruit surface of a tomato crop under two different spray water
regimes, and therefore represents an important step forward towards
the development of science-based metrics for Good Agricultural Practices.},
doi = {10.1186/1471-2180-11-81},
issn = {1471-2180},
pubmedid = {21510867},
url = {http://www.biomedcentral.com/1471-2180/11/81}
}
@ARTICLE{Tellez2011,
author = {Tellez, Noelia and Joanny, Geraldine and Escoriza, Jessica and Vilaseca,
Marina and Montanya, Eduard},
title = {Gastrin Treatment Stimulates {beta}-Cell Regeneration and Improves
Glucose Tolerance in 95% Pancreatectomized Rats},
journal = {Endocrinology},
year = {2011},
volume = {152},
pages = {2580-2588},
number = {7},
abstract = {{beta}-Cell mass reduction is a central aspect in the development
of type 1 and type 2 diabetes, and substitution or regeneration of
the lost {beta}-cells is a potentially curative treatment of diabetes.
To study the effects of gastrin on {beta}-cell mass in rats with
95% pancreatectomy (95%-Px), a model of pancreatic regeneration,
rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17
(Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats,
gastrin treatment reduced hyperglycemia (280 {+/-} 52 mg vs. 436
{+/-} 51 mg/dl, P < 0.05), and increased {beta}-cell mass (1.15 {+/-}
0.15 mg)) compared with vehicle-treated rats (0.67 {+/-} 0.15 mg,
P < 0.05). Gastrin treatment induced {beta}-cell regeneration by
enhancing {beta}-cell neogenesis (increased number of extraislet
{beta}-cells in Px+G: 0.42 {+/-} 0.05 cells/mm2 vs. Px+V: 0.27 {+/-}
0.07 cells/mm2, P < 0.05, and pancreatic and duodenal homeobox 1
expression in ductal cells of Px+G: 1.21 {+/-} 0.38% vs. Px+V: 0.23
{+/-} 0.10%, P < 0.05) and replication (Px+G: 1.65 {+/-} 0.26% vs.
S+V: 0.64 {+/-} 0.14%; P < 0.05). In addition, reduced {beta}-cell
apoptosis contributed to the increased {beta}-cell mass in gastrin-treated
rats (Px+G: 0.07 {+/-} 0.02%, Px+V: 0.23 {+/-} 0.05%; P < 0.05).
Gastrin action on {beta}-cell regeneration and survival increased
{beta}-cell mass and improved glucose tolerance in 95% Px rats, supporting
a potential role of gastrin in the treatment of diabetes.},
doi = {10.1210/en.2011-0066},
eprint = {http://endo.endojournals.org/cgi/reprint/152/7/2580.pdf},
url = {http://endo.endojournals.org/cgi/content/abstract/152/7/2580}
}
@ARTICLE{Tello2008,
author = {Tello, Javier A. and Wu, Sheng and Rivier, Jean E. and Sherwood,
Nancy M.},
title = {Four functional GnRH receptors in zebrafish: analysis of structure,
signaling, synteny and phylogeny},
journal = {Integr. Comp. Biol.},
year = {2008},
volume = {48},
pages = {570--587},
number = {5},
month = nov,
abstract = {Reproduction in all vertebrates requires the brain hormone gonadotropin-releasing
hormone (GnRH) to activate a cascade of events leading to gametogenesis.
All vertebrates studied to date have one to three forms of GnRH in
specific but different neurons in the brain. In addition, at least
one type of GnRH receptor is present in each vertebrate for activation
of specific physiological events within a target cell. Humans possess
two types of GnRH (GnRH1 and GnRH2) but only one functional GnRH
receptor. Zebrafish, Danio rerio, also have two types of GnRH (GnRH2
and GnRH3), although in contrast to humans, zebrafish appear to have
four different GnRH receptors in their genome. To characterize the
biological significance of multiple GnRH receptors within a single
species, we cloned four GnRH receptor cDNAs from zebrafish and compared
their structures, expression, and cell physiology. The zebrafish
receptors are 7-transmembrane G-protein coupled receptors with amino-acid
sequence identities ranging from 45 to 71% among the four receptors.
High sequence similarity was observed among the seven helices of
zebrafish GnRHRs compared with the human GnRHR, the green monkey
type II GnRHR, and the two goldfish GnRHRs. Also, key amino acids
for putative ligand binding, disulfide bond formation, N-glycosylation,
and G-protein coupling were present in the extracellular and intracellular
domains. The four zebrafish receptors were expressed in a variety
of tissues including the brain, eye, and gonads. In an inositol phosphate
assay, each receptor was functional as shown by its response to physiological
doses of native GnRH peptides; two receptors showed selectivity between
GnRH2 and GnRH3. Each of the four receptor genes was mapped to distinct
chromosomes. Our phylogenetic and syntenic analysis segregated the
four zebrafish GnRH receptors into two distinct phylogenetic groups
that are separate gene lineages conserved throughout vertebrate evolution.
We suggest the maintenance of four functional GnRH receptors in zebrafish
compared with only one in humans may depend either on subfunctionalization
or neofunctionalization in fish compared with mammalian GnRH receptors.
The differences in structure, location, and response to GnRH forms
strongly suggests that the four zebrafish GnRH receptors have novel
functions in addition to the conventional activation of the pituitary
gland in the reproductive axis.},
url = {http://icb.oxfordjournals.org/cgi/content/abstract/48/5/570}
}
@ARTICLE{Telonis-Scott2009,
author = {Telonis-Scott, M. and Hallas, R. and McKechnie, S.W. and Wee, C.W.
and Hoffmann, A.A.},
title = {Selection for cold resistance alters gene transcript levels in Drosophila
melanogaster},
journal = {Journal of Insect Physiology},
year = {2009},
volume = {55},
pages = {549--555},
number = {6},
month = jun,
abstract = {Microarrays have been used to examine changes in gene expression underlying
responses to selection for increased stress resistance in Drosophila
melanogaster, but changes in expression patterns associated with
increased resistance to cold stress have not been previously reported.
Here we describe such changes in basal expression levels in replicate
lines following selection for increased resistance to chill coma
stress. We found significant up- or down-regulation of expression
in 94 genes on the Affymetrix Genome 2.0 array. Quantitative RT-PCR
was used to confirm changes in expression of six genes. Some of the
identified genes had previously been associated with stress resistance
but no previously identified candidate genes for cold resistance
showed altered patterns of expression. Seven differentially expressed
genes that form a tight chromosomal cluster and an unlinked gene
AnnX may be potentially important for cold adaptation in natural
populations. Artificial selection for chill coma resistance therefore
altered basal patterns of gene expression, but we failed to link
these changes to plastic changes in expression under cold stress
or to previously identified candidate genes for components of cold
resistance.},
issn = {0022-1910},
keywords = {Gene expression, Drosophila, Selection, Plasticity, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T3F-4VM2YT6-6/2/87adbc25d96b6d9a9cb74781900d74f4}
}
@ARTICLE{Telonis-Scott2009a,
author = {Telonis-Scott, Marina and Kopp, Artyom and Wayne, Marta L. and Nuzhdin,
Sergey V. and McIntyre, Lauren M.},
title = {Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue
Specificity and Evolutionary Conservation},
journal = {Genetics},
year = {2009},
volume = {181},
pages = {421--434},
number = {2},
month = feb,
abstract = {Many genes in eukaryotic genomes produce multiple transcripts through
a variety of molecular mechanisms including alternative splicing.
Alternatively spliced transcripts often encode functionally distinct
proteins, indicating that gene regulation at this level makes an
important contribution to organismal complexity. The multilevel splicing
cascade that regulates sex determination and sex-specific development
in Drosophila is a classical example of the role of alternative splicing
in cell differentiation. Recent evidence suggests that a large proportion
of genes in the Drosophila genome may be spliced in a sex-biased
fashion, raising the possibility that alternative splicing may play
a more general role in sexually dimorphic development and physiology.
However, the prevalence of sex-specific splicing and the extent to
which it is shared among genotypes are not fully understood. Genetic
variation in the splicing of key components of the sex determination
pathway is known to influence the expression of downstream target
genes, suggesting that alternative splicing at other loci may also
vary in functionally important ways. In this study, we used exon-specific
microarrays to examine 417 multitranscript genes for evidence of
sex-specific and genotype-specific splicing in 80 different genotypes
of Drosophila melanogaster. Most of these loci showed sex-biased
splicing, whereas genotype-specific splicing was rare. One hundred
thirty-five genes showed different alternative transcript use in
males vs. females. Real-time PCR analysis of 6 genes chosen to represent
a broad range of biological functions showed that most sex-biased
splicing occurs in the gonads. However, somatic tissues, particularly
adult heads, also show evidence of sex-specific splicing. Comparison
of splicing patterns at orthologous loci in seven Drosophila species
shows that sexual biases in alternative exon representation are highly
conserved, indicating that sex-specific splicing is an ancient feature
of Drosophila biology. To investigate potential mechanisms of sex-biased
splicing, we used real-time PCR to examine the expression of six
known regulators of alternative splicing in males vs. females. We
found that all six loci are themselves spliced sex specifically in
gonads and heads, suggesting that regulatory hierarchies based on
alternative splicing may be an important feature of sexual differentiation.},
url = {http://www.genetics.org/cgi/content/abstract/181/2/421}
}
@ARTICLE{Templeton2009,
author = {Templeton, Justin and Nassr, Mohamed and Vazquez-Chona, Felix and
Freeman-Anderson, Natalie and Orr, William and Williams, Robert and
Geisert, Eldon},
title = {Differential response of C57BL/6J mouse and DBA/2J mouse to optic
nerve crush},
journal = {BMC Neuroscience},
year = {2009},
volume = {10},
pages = {90},
number = {1},
abstract = {BACKGROUND:Retinal ganglion cell (RGC) death is the final consequence
of many blinding diseases, where there is considerable variation
in the time course and severity of RGC loss. Indeed, this process
appears to be influenced by a wide variety of genetic and environmental
factors. In this study we explored the genetic basis for differences
in ganglion cell death in two inbred strains of mice.RESULTS:We found
that RGCs are more susceptible to death following optic nerve crush
in C57BL/6J mice (54% survival) than in DBA/2J mice (62% survival).
Using the Illumina Mouse-6 microarray, we identified 1,580 genes
with significant change in expression following optic nerve crush
in these two strains of mice. Our analysis of the changes occurring
after optic nerve crush demonstrated that the greatest amount of
change (44% of the variance) was due to the injury itself. This included
changes associated with ganglion cell death, reactive gliosis, and
abortive regeneration. The second pattern of gene changes (23% of
the variance) was primarily related to differences in gene expressions
observed between the C57BL/6J and DBA/2J mouse strains. The remaining
changes in gene expression represent interactions between the effects
of optic nerve crush and the genetic background of the mouse. We
extracted one genetic network from this dataset that appears to be
related to tissue remodeling. One of the most intriguing sets of
changes included members of the crystallin family of genes, which
may represent a signature of pathways modulating the susceptibility
of cells to death.CONCLUSION:Differential responses to optic nerve
crush between two widely used strains of mice were used to define
molecular networks associated with ganglion cell death and reactive
gliosis. These results form the basis for our continuing interest
in the modifiers of retinal injury.},
doi = {10.1186/1471-2202-10-90},
issn = {1471-2202},
pubmedid = {19643015},
url = {http://www.biomedcentral.com/1471-2202/10/90}
}
@ARTICLE{Templin2011,
author = {Templin, Thomas and Paul, Sunirmal and Amundson, Sally A. and Young,
Erik F. and Barker, Christopher A. and Wolden, Suzanne L. and Smilenov,
Lubomir B.},
title = {Radiation-Induced Micro-RNA Expression Changes in Peripheral Blood
Cells of Radiotherapy Patients},
journal = {International Journal of Radiation Oncology*Biology*Physics},
year = {2011},
volume = {80},
pages = {549--557},
number = {2},
month = jun,
abstract = {Purpose MicroRNAs (miRNAs), a class of noncoding small RNAs that regulate
gene expression, are involved in numerous physiologic processes in
normal and malignant cells. Our in vivo study measured miRNA and
gene expression changes in human blood cells in response to ionizing
radiation, to develop miRNA signatures that can be used as biomarkers
for radiation exposure.Methods and Materials Blood from 8 radiotherapy
patients in complete remission 1 or 2 was collected immediately before
and 4 hours after total body irradiation with 1.25 Gy x-rays. Both
miRNA and gene expression changes were measured by means of quantitative
polymerase chain reaction and microarray hybridization, respectively.
Hierarchic clustering, multidimensional scaling, class prediction,
and gene ontology analysis were performed to investigate the potential
of miRNAs to serve as radiation biomarkers and to elucidate their
likely physiologic roles in the radiation response.Results The expression
levels of 45 miRNAs were statistically significantly upregulated
4 hours after irradiation with 1.25 Gy x-rays, 27 of them in every
patient. Nonirradiated and irradiated samples form separate clusters
in hierarchic clustering and multidimensional scaling. Out of 223
differentially expressed genes, 37 were both downregulated and predicted
targets of the upregulated miRNAs. Paired and unpaired miRNA-based
classifiers that we developed can predict the class membership of
a sample with unknown irradiation status, with accuracies of 100%
when all 45 upregulated miRNAs are included. Both miRNA control of
and gene involvement in biologic processes such as hemopoiesis and
the immune response are increased after irradiation, whereas metabolic
processes are underrepresented among all differentially expressed
genes and the genes controlled by miRNAs.Conclusions Exposure to
ionizing radiation leads to the upregulation of the expression of
a considerable proportion of the human miRNAome of peripheral blood
cells. These miRNA expression signatures can be used as biomarkers
of radiation exposure.},
issn = {0360-3016},
keywords = {miRNA expression, Gene expression, Peripheral blood cells, Radiotherapy
patients, Biodosimetry},
url = {http://www.sciencedirect.com/science/article/pii/S0360301611000654}
}
@ARTICLE{Tenea2011,
author = {Tenea, Gabriela and Peres Bota, Adrian and Cordeiro Raposo, Fernando
and Maquet, Alain},
title = {Reference genes for gene expression studies in wheat flag leaves
grown under different farming conditions},
journal = {BMC Research Notes},
year = {2011},
volume = {4},
pages = {373},
number = {1},
abstract = {BACKGROUND:Internal control genes with highly uniform expression throughout
the experimental conditions are required for accurate gene expression
analysis as no universal reference genes exists. In this study, the
expression stability of 24 candidate genes from Triticum aestivum
cv. Cubus flag leaves grown under organic and conventional farming
systems was evaluated in two locations in order to select suitable
genes that can be used for normalization of real-time quantitative
reverse-transcription PCR (RT-qPCR) reactions. The genes were selected
among the most common used reference genes as well as genes encoding
proteins involved in several metabolic pathways.FINDINGS:Individual
genes displayed different expression rates across all samples assayed.
Applying geNorm, a set of three potential reference genes were suitable
for normalization of RT-qPCR reactions in winter wheat flag leaves
cv. Cubus: TaFNRII (ferredoxin-NADP(H) oxidoreductase; AJ457980.1),
ACT2 (actin 2; TC234027), and rrn26 (a putative homologue to RNA
26S gene; AL827977.1). In addition of these three genes that were
also top-ranked by NormFinder, two extra genes: CYP18-2 (Cyclophilin
A, AY456122.1) and TaWIN1 (14-3-3 like protein, AB042193) were most
consistently stably expressed.Furthermore, we showed that TaFNRII,
ACT2, and CYP18-2 are suitable for gene expression normalization
in other two winter wheat varieties (Tommi and Centenaire) grown
under three treatments (organic, conventional and no nitrogen) and
a different environment than the one tested with cv. Cubus.CONCLUSIONS:This
study provides a new set of reference genes which should improve
the accuracy of gene expression analyses when using wheat flag leaves
as those related to the improvement of nitrogen use efficiency for
cereal production.},
doi = {10.1186/1756-0500-4-373},
issn = {1756-0500},
pubmedid = {21951810},
url = {http://www.biomedcentral.com/1756-0500/4/373}
}
@ARTICLE{Teng2010,
author = {Teng, Allen C. T. and Kuraitis, Drew and Deeke, Shelley A. and Ahmadi,
Ali and Dugan, Stephen G. and Cheng, Brian L. M. and Crowson, Matthew
G. and Burgon, Patrick G. and Suuronen, Erik J. and Chen, Hsiao-Huei
and Stewart, Alexandre F. R.},
title = {IRF2BP2 is a skeletal and cardiac muscle-enriched ischemia-inducible
activator of VEGFA expression},
journal = {FASEB J},
year = {2010},
pages = {fj.10-167049--},
month = aug,
abstract = {We sought to identify an essential component of the TEAD4/VGLL4 transcription
factor complex that controls vascular endothelial growth factor A
(VEGFA) expression in muscle. A yeast 2-hybrid screen was used to
clone a novel component of the TEAD4 complex from a human heart cDNA
library. We identified interferon response factor 2 binding protein
2 (IRF2BP2) and confirmed its presence in the TEAD4/VGLL4 complex
in vivo by coimmunoprecipitation and mammalian 2-hybrid assays. Coexpression
of IRF2BP2 with TEAD4/VGLL4 or TEAD1 alone potently activated, whereas
knockdown of IRF2BP2 reduced, VEGFA expression in C2C12 muscle cells.
Thus, IRF2BP2 is required to activate VEGFA expression. In mouse
embryos, IRF2BP2 was ubiquitously expressed but became progressively
enriched in the fetal heart, skeletal muscles, and lung. Northern
blot analysis revealed high levels of IRF2BP2 mRNA in adult human
heart and skeletal muscles, but immunoblot analysis showed low levels
of IRF2BP2 protein in skeletal muscle, indicating post-transcriptional
regulation of IRF2BP2 expression. IRF2BP2 protein levels are markedly
increased by ischemia in skeletal and cardiac muscle compared to
normoxic controls. IRF2BP2 is a novel ischemia-induced coactivator
of VEGFA expression that may contribute to revascularization of ischemic
cardiac and skeletal muscles.--Teng, A. C. T., Kuraitis, D., Deeke,
S. A., Ahmadi, A., Dugan, S. G., Cheng, B. L. M., Crowson, M. G.,
Burgon, P. G., Suuronen, E. J., Chen, H.-H., Stewart, A. F. R. IRF2BP2
is a skeletal and cardiac muscle-enriched ischemia-inducible activator
of VEGFA expression.},
url = {http://www.fasebj.org/cgi/content/abstract/fj.10-167049v2}
}
@ARTICLE{Tenger2005,
author = {Tenger, Charlotta and Sundborger, Anna and Jawien, Jacek and Zhou,
Xinghua},
title = {IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN-{gamma}
and CXCL16 Expression Independently of T Cells},
journal = {Arterioscler Thromb Vasc Biol},
year = {2005},
volume = {25},
pages = {791--796},
number = {4},
month = apr,
abstract = {Objective-- The proatherogenic effect of IL-18 is shown to be dependent
on IFN-{gamma} production. It is believed that activated T cells
play a proatherogenic role through secretion of IFN-{gamma}. However,
recent studies in vitro have shown that macrophages, NK cells, and
even vascular smooth muscle cells may also secrete IFN-{gamma} after
stimulation by cytokines like IL-18. We therefore investigated whether
cells other than activated T cells can play a proatherogenic role
via IFN-{gamma} secretion under the stimulation of IL-18 in vivo.
Methods and Results-- SCID/apoE knockout mice were injected intraperitoneally
with either IL-18 or phosphate-buffered saline 3 times per week for
7 weeks. Our results show that administration of IL-18 leads to 3-fold
larger lesions and 2-fold higher circulating IFN-{gamma} despite
the absence of T cells. In addition, increased IFN-{gamma}, accompanied
by elevation of the scavenger receptor/chemokine CXCL16, was observed
in both lesions and spleens. Furthermore, our findings revealed that
macrophages, NK cells, and vascular cells were the source of IFN-{gamma}
under the stimulation of IL-18 in the absence of T cells in vivo.
Conclusion-- The current data suggest that the proatherogenic effect
of IL-18 can occur in the absence of T cells and that IFN-{gamma}
secreted by macrophages, NK cells, and vascular cells is sufficient
for the disease progression. To investigate whether cells other than
T cells play a proatherogenic role via secretion of IFN-{gamma},
we used SCID/apoE knockout mice. Administration of IL-18 resulted
in larger lesions and elevated IFN-{gamma}. Our data suggest that
IFN-{gamma} from macrophages, NK cells, and vascular cells in vivo
is sufficient for the disease progression.},
url = {http://atvb.ahajournals.org/cgi/content/abstract/25/4/791}
}
@ARTICLE{Teoh2011,
author = {Teoh, Deanna and Ayeni, Tina A. and Rubatt, Jennifer M. and Adams,
David J. and Grace, Lisa and Starr, Mark D. and Barry, William T.
and Berchuck, Andrew and Murphy, Susan K. and Secord, Angeles Alvarez},
title = {Dasatinib (BMS-35482) has synergistic activity with paclitaxel and
carboplatin in ovarian cancer cells},
journal = {Gynecologic Oncology},
year = {2011},
volume = {121},
pages = {187--192},
number = {1},
month = apr,
abstract = {Purpose To explore the activity of dasatinib alone and in combination
with paclitaxel and carboplatin in ovarian cancer cells and to determine
if dasatinib activity can be predicted based on evaluation of the
SRC pathway.Experimental design Microarray analysis was performed
for IGROV1, OVCAR3, A2780 and SKOV3 ovarian cancer cells and the
status of the genomic SRC signature pathway was determined. Cells
were treated with carboplatin, paclitaxel and dasatinib individually
and in combination. Pre- and post-treatment phospho-SRC (pSRC) and
SRC protein expression was determined. Dose-response curves were
constructed, and drug interaction was assessed by the Combination
Index (CI) method.Results SRC protein expression levels reflected
the SRC pathway genomic signature in the cell lines with the lowest
(SKOV3) and highest (IGROV1) pathway expression, but not in those
with intermediate expression (OVCAR3, A2780). Dasatinib treatment
caused loss of pSRC in all cell lines, with 50% growth inhibition
for IGROV1 at 70 nM, OVCAR3 at 34 nM, A2780 at 4.1 [mu]M and SKOV3
at 530 nM. Dasatinib combined with cytotoxics yielded a synergistic
effect (CI = 0.46 to 0.79) in all cell lines except SKOV3.Conclusion
Dasatinib in combination with standard chemotherapeutic agents appears
to interact in a synergistic manner in some ovarian cancer cell lines.
Further research is needed to evaluate tumor cell characteristics
which predict response to dasatinib.},
booktitle = {New Biomarkers and Risk Predictors for Prevention and Early Detection
of Gynecologic Cancers},
issn = {0090-8258},
keywords = {SRC pathway, Dasatinib, Ovarian cancer},
url = {http://www.sciencedirect.com/science/article/pii/S0090825810008437}
}
@ARTICLE{Tepaamorndech2011,
author = {Surapun Tepaamorndech and Liping Huang and Catherine P. Kirschke},
title = {A null-mutation in the Znt7 gene accelerates prostate tumor formation
in a transgenic adenocarcinoma mouse prostate model},
journal = {Cancer Letters},
year = {2011},
volume = {308},
pages = {33 - 42},
number = {1},
abstract = {Decrease of cellular zinc in the epithelium of the prostate has been
implicated in the development of prostate cancer. To investigate
whether ZnT7, a zinc transporter involved in intracellular zinc accumulation,
played a role in prostate cancer development, we generated and characterized
a transgenic adenocarcinoma mouse prostate (TRAMP) model with a Znt7-null
genetic background. TRAMP mice (TRAMP/Znt7−/− and TRAMP/Znt7+/+)
were euthanized at 6, 8, 16, and 28 weeks of age for histopathological
analysis of the prostates and for the presence of prostate tumors
and metastasis. At 6 and 8 weeks of age, TRAMP/Znt7−/− mice
displayed higher frequencies of low grade prostatic intraepithelial
neoplasia (PIN) and high grade PIN, respectively, in the prostates
than the age-matched TRAMP/Znt7+/+ mice. At 16 weeks of age,
33% TRAMP/Znt7−/− mice had prostate tumors and one half of the
mice with prostate tumors had tumor metastasized to the draining
lymph nodes while no prostate tumor was detected in the control TRAMP
mice. By 28 weeks, 67% TRAMP/Znt7−/− mice developed prostate
tumors while only 22% control TRAMP mice had prostate tumors. Furthermore,
apoptosis was reduced in the prostates of TRAMP/Znt7−/− mice.
In conclusion, a null-mutation of the Znt7 gene accelerates prostate
tumor formation in TRAMP mice.},
doi = {10.1016/j.canlet.2011.04.011},
issn = {0304-3835},
keywords = {Znt7},
url = {http://www.sciencedirect.com/science/article/pii/S0304383511002229}
}
@ARTICLE{Teramoto2009,
author = {Teramoto, Maki and Suzuki, Masahito and Okazaki, Fumiyoshi and Hatmanti,
Ariani and Harayama, Shigeaki},
title = {Oceanobacter-related bacteria are important for the degradation of
petroleum aliphatic hydrocarbons in the tropical marine environment},
journal = {Microbiology},
year = {2009},
volume = {155},
pages = {3362--3370},
number = {10},
month = oct,
abstract = {Petroleum-hydrocarbon-degrading bacteria were obtained after enrichment
on crude oil (as a chocolate mousse') in a continuous supply of Indonesian
seawater amended with nitrogen, phosphorus and iron nutrients. They
were related to Alcanivorax and Marinobacter strains, which are ubiquitous
petroleum-hydrocarbon-degrading bacteria in marine environments,
and to Oceanobacter kriegii (96.4-96.5 % similarities in almost full-length
16S rRNA gene sequences). The Oceanobacter-related bacteria showed
high n-alkane-degrading activity, comparable to that of Alcanivorax
borkumensis strain SK2. On the other hand, Alcanivorax strains exhibited
high activity for branched-alkane degradation and thus could be key
bacteria for branched-alkane biodegradation in tropical seas. Oceanobacter-related
bacteria became most dominant in microcosms that simulated a crude
oil spill event with Indonesian seawater. The dominance was observed
in microcosms that were unamended or amended with fertilizer, suggesting
that the Oceanobacter-related strains could become dominant in the
natural tropical marine environment after an accidental oil spill,
and would continue to dominate in the environment after biostimulation.
These results suggest that Oceanobacter-related bacteria could be
major degraders of petroleum n-alkanes spilt in the tropical sea.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/155/10/3362}
}
@ARTICLE{Terrat2010,
author = {Terrat, Sébastien and Peyretaillade, Eric and Gonçalves, Olivier
and Dugat-Bony, Eric and Gravelat, Fabrice and Moné, Anne and Biderre-Petit,
Corinne and Boucher, Delphine and Troquet, Julien and Peyret, Pierre},
title = {Detecting variants with Metabolic Design, a new software tool to
design probes for explorative functional DNA microarray development},
journal = {BMC Bioinformatics},
year = {2010},
volume = {11},
pages = {478},
number = {1},
abstract = {BACKGROUND:Microorganisms display vast diversity, and each one has
its own set of genes, cell components and metabolic reactions. To
assess their huge unexploited metabolic potential in different ecosystems,
we need high throughput tools, such as functional microarrays, that
allow the simultaneous analysis of thousands of genes. However, most
classical functional microarrays use specific probes that monitor
only known sequences, and so fail to cover the full microbial gene
diversity present in complex environments. We have thus developed
an algorithm, implemented in the user-friendly program Metabolic
Design, to design efficient explorative probes.RESULTS:First we have
validated our approach by studying eight enzymes involved in the
degradation of polycyclic aromatic hydrocarbons from the model strain
Sphingomonas paucimobilis sp. EPA505 using a designed microarray
of 8,048 probes. As expected, microarray assays identified the targeted
set of genes induced during biodegradation kinetics experiments with
various pollutants. We have then confirmed the identity of these
new genes by sequencing, and corroborated the quantitative discrimination
of our microarray by quantitative real-time PCR. Finally, we have
assessed metabolic capacities of microbial communities in soil contaminated
with aromatic hydrocarbons. Results show that our probe design (sensitivity
and explorative quality) can be used to study a complex environment
efficiently.CONCLUSIONS:We successfully use our microarray to detect
gene expression encoding enzymes involved in polycyclic aromatic
hydrocarbon degradation for the model strain. In addition, DNA microarray
experiments performed on soil polluted by organic pollutants without
prior sequence assumptions demonstrate high specificity and sensitivity
for gene detection. Metabolic Design is thus a powerful, efficient
tool that can be used to design explorative probes and monitor metabolic
pathways in complex environments, and it may also be used to study
any group of genes. The Metabolic Design software is freely available
from the authors and can be downloaded and modified under general
public license.},
doi = {10.1186/1471-2105-11-478},
issn = {1471-2105},
pubmedid = {20860850},
url = {http://www.biomedcentral.com/1471-2105/11/478}
}
@ARTICLE{Terreni2003,
author = {Terreni, Liana and Fogliarino, Sergio and Quadri, Pierluigi and Ruggieri,
Rosa Maria and Piccoli, Federico and Tettamanti, Mauro and Lucca,
Ugo and Forloni, Gianluigi},
title = {Tumor necrosis factor [alpha] polymorphism C-850T is not associated
with Alzheimer's disease and vascular dementia in an Italian population},
journal = {Neuroscience Letters},
year = {2003},
volume = {344},
pages = {135--137},
number = {2},
month = jun,
abstract = {A pathogenic role of inflammatory factors has been proposed both in
Alzheimer's disease (AD) and vascular dementia (VD). A previous report
indicated the presence of polymorphism C-850T of tumor necrosis factor
(TNF) [alpha] as a genetic risk factor for VD and, associated with
apolipoprotein E [var epsilon]4, for AD. We have assessed the association
between TNF-[alpha] polymorphism and dementias in Italian populations
of AD, VD and elderly controls. The influence of TNF-[alpha] polymorphism
on dementia has not been confirmed in this segment of the Italian
population.},
issn = {0304-3940},
keywords = {Neuroinflammation, Dementia, Cytokines, Genetic risk, Apolipoprotein
E},
url = {http://www.sciencedirect.com/science/article/B6T0G-48N3H2W-2/2/417ef62634857d6d7db954eac724dd3f}
}
@ARTICLE{Terreros2011,
author = {Terreros, Maria C and Rowold, Diane J and Mirabal, Sheyla and Herrera,
Rene J},
title = {Mitochondrial DNA and Y-chromosomal stratification in Iran: relationship
between Iran and the Arabian Peninsula},
journal = {J Hum Genet},
year = {2011},
volume = {56},
pages = {235--246},
number = {3},
month = mar,
issn = {1434-5161},
publisher = {The Japan Society of Human Genetics},
url = {http://dx.doi.org/10.1038/jhg.2010.174}
}
@ARTICLE{Terribas2010,
author = {Terribas, Ernest and Bonache, Sandra and Garcia-arevalo, Marta and
Sanchez, Josvany and Franco, Eladio and Bassas, Lluis and Larriba,
Sara},
title = {Changes in the Expression Profile of the Meiosis-Involved Mismatch
Repair Genes in Impaired Human Spermatogenesis},
journal = {J Androl},
year = {2010},
volume = {31},
pages = {346--357},
number = {4},
month = jul,
abstract = {DNA mismatch repair (MMR) genes have been described to participate
in crossover events during meiotic recombination, which is, in turn,
a key step of spermatogenesis. This evidence suggests that MMR family
gene expression may be altered in infertile men with defective sperm
production. In order to determine the expression profile of MMR genes
in impaired human spermatogenesis, we performed transcript levels
analysis of MMR genes (MLH1, MLH3, PMS2, MSH4, and MSH5), and other
meiosis-involved genes (ATR, HSPA2, and SYCP3) as controls, by real-time
reverse transcription-polymerase chain reaction in testis from 13
patients with spermatogenic failure, 5 patients with primary germ
cell tumors, and 10 controls with conserved spermatogenesis. Correlation
of the expression values with the histological findings was also
performed. The MMR gene expression values, with the exception of
PMS2, are significantly decreased in men with spermatogenic failure.
The pattern of MMR reduction correlates with the severity of damage,
being maximum in maturation arrest. Specifically, expression of the
testicular MSH4 gene could be useful as a surrogate marker for the
presence of intratesticular elongated spermatid in patients with
nonobstructive azoospermia, contributing to predict the viability
of assisted reproduction. Interestingly, a reduction in the MSH4
and MSH5 transcript concentration per spermatocyte was also observed.
The decreased expression level of other meiosis-specific genes, such
as HSPA2 and SYCP3, suggests that the spermatocyte capacity to express
meiosis-related genes is markedly reduced in spermatogenic failure,
contributing to meiosis impairment and spermatogenic blockade.},
url = {http://www.andrologyjournal.org/cgi/content/abstract/31/4/346}
}
@ARTICLE{Terrien2011,
author = {Xavier Terrien and Jean-Baptiste Fini and Barbara A. Demeneix and
Karl-Werner Schramm and Patrick Prunet},
title = {Generation of fluorescent zebrafish to study endocrine disruption
and potential crosstalk between thyroid hormone and corticosteroids},
journal = {Aquatic Toxicology},
year = {2011},
volume = {105},
pages = {13 - 20},
number = {1–2},
abstract = {Several environmental chemicals disrupt thyroid function, a key regulator
of normal development involved in many physiological processes in
fish. We studied the effects of such chemicals in vivo using transient
transgenic zebrafish (Danio rerio), expressing Green Fluorescent
Protein (GFP) under the control of a TH/bZIP promoter from Xenopus
laevis. Exposure to thyroid hormone (T3) at 10−8 M increased
GFP fluorescence in F0 embryos and larvae. Transient transgenic embryos
were exposed to a T3 signaling agonist (TRIAC) or antagonists (NH3
or NaClO4), or to the endocrine disruptor Bisphenol A (BPA). When
tested alone, TRIAC increased fluorescence, confirming the specificity
of our model. Exposure to NH3 or NaClO4 decreased fluorescence, reflecting
inhibition of thyroid function. When tested alone, BPA did not modify
fluorescence, but when tested with T3, it significantly reduced T3-induced
fluorescence, suggesting disruption of the thyroid function by BPA.
The expression of genes involved in the TH axis (TR-alpha, TR-beta,
TSH) and the corticoid axis (GR and MR) was followed by q-PCR after
T3 or BPA exposure (24 or 48 h) and at different developmental
stages (0, 1, or 5 days post-fertilization). Expression of TR-alpha,
TR-beta, and TSH genes increased after 48 h T3 exposure in 1-day-old
larvae. When tested alone, BPA only slightly affected gene expression.
When applied with T3, BPA decreased expression of all candidate genes
in 1-day-old embryos compared to the T3 treated group, in agreement
with data obtained with the TH/bZIP-eGFP zebrafish model. Finally,
we show that T3 exposure leads to up-regulation of MR and GR genes.
This study provides a new rapid diagnostic tool for characterizing
the disrupting effects of toxicants on thyroid function and suggests
possible crosstalk between the TR and Corticoid Signaling system.},
doi = {10.1016/j.aquatox.2011.04.007},
issn = {0166-445X},
keywords = {Zebrafish},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X11001056}
}
@ARTICLE{Terrier2011,
author = {Terrier, Benjamin and Joly, Florence and Vazquez, Thomas and Benech,
Philippe and Rosenzwajg, Michelle and Carpentier, Wassila and Garrido,
Marlene and Ghillani-Dalbin, Pascale and Klatzmann, David and Cacoub,
Patrice and Saadoun, David},
title = {Expansion of Functionally Anergic CD21-/low Marginal Zone-like B
Cell Clones in Hepatitis C Virus Infection-Related Autoimmunity},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {6550-6563},
number = {12},
abstract = {Homeostasis of peripheral B cell subsets is disturbed during chronic
hepatitis C virus (HCV) infection, leading to the occurrence of autoimmunity
and B cell lymphoproliferation. However, mechanisms by which HCV
causes lymphoproliferation remain controversial. We report in this
article on the elevated number of clonal CD21-/lowIgM+CD27+ marginal
zone (MZ)-like B cells, which correlates with autoimmunity and lymphoproliferation
in HCV patients. We found an increase in autoreactive BCRs using
VH1-69 and VH4-34 genes in CD21-/low MZ B cells. CD21-/low MZ B cells
showed impaired calcium-mediated signaling, did not upregulate activation
markers, and did not proliferate in response to BCR triggering. CD21-/low
MZ B cells also were prone to dying faster than their CD21+ counterparts,
suggesting that these B cells were anergic. CD21-/low MZ B cells,
in contrast, remained responsive to TLR9 stimulation. Gene array
analyses revealed the critical role of Early growth response 2 and
Cbl-b in the induction of anergy. Therefore, HCV patients who display
high frequencies of unresponsive CD21-/low MZ B cells are more susceptible
to developing autoimmunity and/or lymphoproliferation. These cells
remain in peripheral blood controlled by functional anergy instead
of being eliminated, and chronic antigenic stimulation through TLR
stimulation may create a favorable environment for breaking tolerance
and activating these cells.},
doi = {10.4049/jimmunol.1102022},
eprint = {http://www.jimmunol.org/cgi/reprint/187/12/6550.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/12/6550}
}
@ARTICLE{Terry2006,
author = {Terry, Jonathan G. and Campbell, Colin J. and Ross, Alan J. and Livingston,
Andrew D. and Buck, Amy H. and Dickinson, Paul and Mountford, Christopher
P. and Evans, Stuart A. G. and Mount, Andrew R. and Beattie, John
S. and Crain, Jason and Ghazal, Peter and Walton, Anthony J.},
title = {Improved Silicon Nitride Surfaces for Next-Generation Microarrays},
journal = {Langmuir},
year = {2006},
volume = {22},
pages = {11400-11404},
number = {26},
doi = {10.1021/la060489v},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/la060489v},
url = {http://pubs.acs.org/doi/abs/10.1021/la060489v}
}
@ARTICLE{Tesarova2011,
author = {Tesarova, Lenka and Koutna, Irena and Koristek, Zdenek and Klabusay,
Martin},
title = {Multiple myeloma patients at peripheral blood stem cell harvest:
Restricted usage of TCR beta variable families},
journal = {Clinical Immunology},
year = {2011},
volume = {138},
pages = {67--76},
number = {1},
month = jan,
abstract = {The immune systems of multiple myeloma patients are suppressed by
the disease itself, and this immunosuppression is further enhanced
by standard therapies. The aim of our study was to evaluate the effects
of initial chemotherapy and a peripheral blood mobilisation regimen
on T-cell population diversity. Reverse transcription-polymerase
chain reaction (RT-PCR) with a new set of primers, in combination
with capillary electrophoresis, was established. The methodology
was used to analyse the relative expression of 27 T-cell receptor
beta variable gene families (BV families) in multiple myeloma patients
undergoing peripheral blood stem cell harvest. We found that the
overall BV family usage in these patients was restricted; the relative
expression of 10 BV families was significantly depressed in patients
compared to healthy donors. These findings demonstrate that the preparative
regimen for autologous stem cell transplantation affects the T-cell
population in terms of the restriction of its T-cell receptor diversity.},
issn = {1521-6616},
keywords = {T-cell receptor, Beta variable families, Multiple myeloma, Reverse
transcription-polymerase chain reaction, Capillary electrophoresis},
url = {http://www.sciencedirect.com/science/article/pii/S1521661610007187}
}
@ARTICLE{Tesfai2011,
author = {Yordanos Tesfai and Jette Ford and Kim W. Carter and Martin J. Firth
and Rebecca A. O’Leary and Nicholas G. Gottardo and Catherine Cole
and Ursula R. Kees},
title = {Interactions between acute lymphoblastic leukemia and bone marrow
stromal cells influence response to therapy},
journal = {Leukemia Research},
year = {2011},
pages = { - },
number = {0},
abstract = {The cure rate for pediatric patients with B precursor acute lymphoblastic
leukemia (pre-B ALL) is steadily improving, however relapses do occur
despite initial response to therapy. To identify links between drug
resistance and gene deregulation we used oligonucleotide microarray
technology and determined in 184 pre-B ALL specimen genes differentially
expressed compared to normal CD34+ specimens. We identified 20 signature
genes including CTGF, BMP-2, CXCR4 and IL7R, documented to regulate
interactions in the bone marrow. We recorded remarkably similar levels
of expression in three independent patient cohorts, and found distinct
patterns in cytogenetically defined subgroups of pre-B ALL. The canonical
pathways that were affected are involved in inter- and intra-cellular
communication, regulating signaling within the microenvironment.
We tested experimentally whether interaction with stromal cells conferred
protection to four drugs used in current ALL therapy, and demonstrated
that bone marrow stromal cells significantly influenced resistance
to vincristine and cytosine arabinoside. Compounds designed to block
the identified cellular interactions within the bone marrow microenvironment
are expected to mobilise the leukemic cells and make them more accessible
to contemporary antileukemic agents. The data provide novel insight
into the pathobiology of ALL and indicate new therapeutic targets
for patients with ALL.},
doi = {10.1016/j.leukres.2011.08.001},
issn = {0145-2126},
keywords = {Acute lymphoblastic leukemia},
url = {http://www.sciencedirect.com/science/article/pii/S0145212611003900}
}
@ARTICLE{Tessema2008,
author = {Tessema, Mathewos and Willink, Randy and Do, Kieu and Yu, Yang Y.
and Yu, Wayne and Machida, Emi O. and Brock, Malcolm and Van Neste,
Leander and Stidley, Christine A. and Baylin, Stephen B. and Belinsky,
Steven A.},
title = {Promoter Methylation of Genes in and around the Candidate Lung Cancer
Susceptibility Locus 6q23-25},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {1707--1714},
number = {6},
month = mar,
abstract = {Chromosomal aberrations associated with lung cancer are frequently
observed in the long arm of chromosome 6. A candidate susceptibility
locus at 6q23-25 for lung cancer was recently identified; however,
no tumor suppressor genes inactivated by mutation have been identified
in this locus. Genetic, epigenetic, gene expression, and in silico
screening approaches were used to select 43 genes located in 6q12-27
for characterization of methylation status. Twelve (28%) genes were
methylated in at least one lung cancer cell line, and methylation
of 8 genes was specific to lung cancer cell lines. Five of the 8
genes with the highest prevalence for methylation in cell lines (TCF21,
SYNE1, AKAP12, IL20RA, and ACAT2) were examined in primary lung adenocarcinoma
samples from smokers (n = 100) and never smokers (n = 75). The prevalence
for methylation of these genes was 81%, 50%, 39%, 26%, and 14%, respectively,
and did not differ by smoking status or age at diagnosis. Transcription
of SYNE1, AKAP12, and IL20RA was completely silenced by hypermethylation
and could be restored after treatment with 5-aza-2-deoxycytidine.
Significant associations were found between methylation of SYNE1
and TCF21, SYNE1 and AKAP12, and AKAP12 and IL20RA, indicating a
coordinated inactivation of these genes in tumors. A higher prevalence
for methylation of these genes was not associated with early-onset
lung cancer cases, most likely precluding their involvement in familial
susceptibility to this disease. Together, our results indicate that
frequent inactivation of multiple candidate tumor suppressor genes
within chromosome 6q likely contributes to development of sporadic
lung cancer. [Cancer Res 2008;68(6):1707-14]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/6/1707}
}
@ARTICLE{Teste2009,
author = {Teste, Marie-Ange and Duquenne, Manon and François, Jean and Parrou,
Jean-Luc},
title = {Validation of reference genes for quantitative expression analysis
by real-time RT-PCR in Saccharomyces cerevisiae},
journal = {BMC Molecular Biology},
year = {2009},
volume = {10},
pages = {99},
number = {1},
abstract = {BACKGROUND:Real-time RT-PCR is the recommended method for quantitative
gene expression analysis. A compulsory step is the selection of good
reference genes for normalization. A few genes often referred to
as HouseKeeping Genes (HSK), such as ACT1, RDN18 or PDA1 are among
the most commonly used, as their expression is assumed to remain
unchanged over a wide range of conditions. Since this assumption
is very unlikely, a geometric averaging of multiple, carefully selected
internal control genes is now strongly recommended for normalization
to avoid this problem of expression variation of single reference
genes. The aim of this work was to search for a set of reference
genes for reliable gene expression analysis in Saccharomyces cerevisiae.RESULTS:From
public microarray datasets, we selected potential reference genes
whose expression remained apparently invariable during long-term
growth on glucose. Using the algorithm geNorm, ALG9, TAF10, TFC1
and UBC6 turned out to be genes whose expression remained stable,
independent of the growth conditions and the strain backgrounds tested
in this study. We then showed that the geometric averaging of any
subset of three genes among the six most stable genes resulted in
very similar normalized data, which contrasted with inconsistent
results among various biological samples when the normalization was
performed with ACT1. Normalization with multiple selected genes was
therefore applied to transcriptional analysis of genes involved in
glycogen metabolism. We determined an induction ratio of 100-fold
for GPH1 and 20-fold for GSY2 between the exponential phase and the
diauxic shift on glucose. There was no induction of these two genes
at this transition phase on galactose, although in both cases, the
kinetics of glycogen accumulation was similar. In contrast, SGA1
expression was independent of the carbon source and increased by
3-fold in stationary phase.CONCLUSION:In this work, we provided a
set of genes that are suitable reference genes for quantitative gene
expression analysis by real-time RT-PCR in yeast biological samples
covering a large panel of physiological states. In contrast, we invalidated
and discourage the use of ACT1 as well as other commonly used reference
genes (PDA1, TDH3, RDN18, etc) as internal controls for quantitative
gene expression analysis in yeast.},
doi = {10.1186/1471-2199-10-99},
issn = {1471-2199},
pubmedid = {19874630},
url = {http://www.biomedcentral.com/1471-2199/10/99}
}
@ARTICLE{Teste2010,
author = {Teste, Marie-Ange and Francois, Jean Marie and Parrou, Jean-Luc},
title = {Characterization of a New Multigene Family Encoding Isomaltases in
the Yeast Saccharomyces cerevisiae, the IMA Family},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {26815--26824},
number = {35},
month = aug,
abstract = {It has been known for a long time that the yeast Saccharomyces cerevisiae
can assimilate {alpha}-methylglucopyranoside and isomaltose. We here
report the identification of 5 genes (YGR287c, YIL172c, YJL216c,
YJL221c and YOL157c), which, similar to the SUCx, MALx, or HXTx multigene
families, are located in the subtelomeric regions of different chromosomes.
They share high nucleotide sequence identities between themselves
(66-100%) and with the MALx2 genes (63-74%). Comparison of their
amino acid sequences underlined a substitution of threonine by valine
in region II, one of the four highly conserved regions of the {alpha}-glucosidase
family. This change was previously shown to be sufficient to discriminate
{alpha}-1,4- to {alpha}-1,6-glucosidase activity in YGR287c (Yamamoto,
K., Nakayama, A., Yamamoto, Y., and Tabata, S. (2004) Eur. J. Biochem.
271, 3414-3420). We showed that each of these five genes encodes
a protein with {alpha}-glucosidase activity on isomaltose, and we
therefore renamed these genes IMA1 to IMA5 for IsoMAltase. Our results
also illustrated that sequence polymorphisms among this family led
to interesting variability of gene expression patterns and of catalytic
efficiencies on different substrates, which altogether should account
for the absence of functional redundancy for growth on isomaltose.
Indeed, deletion studies revealed that IMA1/YGR287c encodes the major
isomaltase and that growth on isomaltose required the presence of
AGT1, which encodes an {alpha}-glucoside transporter. Expressions
of IMA1 and IMA5/YJL216c were strongly induced by maltose, isomaltose,
and {alpha}-methylglucopyranoside, in accordance with their regulation
by the Malx3p-transcription system. The physiological relevance of
this IMAx multigene family in S. cerevisiae is discussed.},
url = {http://www.jbc.org/cgi/content/abstract/285/35/26815}
}
@ARTICLE{Teuffel2004,
author = {Teuffel, O and Dettling, M and Cario, G and Stanulla, M and Schrappe,
M and Buhlmann, P and Niggli, FK and Schafer, BW},
title = {Gene expression profiles and risk stratification in childhood acute
lymphoblastic leukemia},
journal = {Haematologica},
year = {2004},
volume = {89},
pages = {801--808},
number = {7},
month = jul,
abstract = {BACKGROUND AND OBJECTIVES: Childhood acute lymphoblastic leukemia
(ALL) is a heterogeneous disease. There are several distinct genetic
subtypes, characterized by typical changes in gene expression pattern.
In addition to cytogenetic markers, the in vivo response to treatment
is an emerging prognostic marker for risk stratification. However,
it has not yet been reported whether gene expression profiles can
predict risk group stratification already at the time of diagnosis.
DESIGN AND METHODS: We analyzed bone marrow samples of 31 ALL patients
to identify changes in gene expression that are associated with the
current risk assignment, irrespective of the genetic subtype. Gene
expression profiles were established using oligonucleotide microarrays.
RESULTS: Considering all low- and high-risk patients, no gene was
capable of predicting the risk assignment already at time of diagnosis.
However, screening for risk group associated genes using more homogeneous
subsets of patients revealed 10(6) discriminatory probe sets. The
prognostic significance of these probe sets was subsequently determined
for the entire series of patients. Using the selected subgroups as
the training set and the remaining samples as an independent test
set, logistic regression using 3 predictor variables could accurately
predict current risk assignment for 10 out of 12 patients. INTERPRETATION
AND CONCLUSIONS: Gene expression profiles established from a cytogenetically
heterogeneous study group are not, as yet, sufficiently accurate
to be used prognostically in a clinical setting. Additional risk-associated
gene expression analyses need to be performed in more homogeneous
sets of patients.},
url = {http://www.haematologica.org/cgi/content/abstract/89/7/801}
}
@ARTICLE{Tew2011,
author = {S.R. Tew and O. Vasieva and M.J. Peffers and P.D. Clegg},
title = {Post-transcriptional gene regulation following exposure of osteoarthritic
human articular chondrocytes to hyperosmotic conditions},
journal = {Osteoarthritis and Cartilage},
year = {2011},
volume = {19},
pages = {1036 - 1046},
number = {8},
abstract = {SummaryObjective Osmolarity is a major biophysical regulator of chondrocyte
function. Modulation of chondrocytic marker gene expression occurs
at the post-transcriptional level following exposure of human articular
chondrocytes (HAC) to hyperosmotic conditions. This study aims to
further characterise the post-transcriptional response of HAC to
hyperosmolarity. Methods Gene expression and microRNA (miRNA) levels
in freshly isolated HAC after 5 h under control or hyperosmotic
conditions were measured using microarrays. Regulated genes were
checked for the presence of AU rich elements (AREs) in their 3′
untranslated regions (3′UTR), whilst gene ontology was examined
using Ingenuity Pathway Analysis (IPA). RNA decay rates of candidate
ARE-containing genes were determined in HAC using actinomycin D chase
experiments and the involvement of the p38 mitogen-activated protein
kinase (MAPK) and extracellular signal-regulated kinases 1 and 2
(ERK1/2) pathways were investigated using pharmacological inhibitors.
Results Hyperosmolarity led to the regulation of a wide variety of
genes. IPA identified enrichment of genes involved with cell stress
responses, cell signalling and transforming growth factor β (TGFβ)
signalling. Importantly, upregulated genes were over-represented
with those containing AREs, and RNA decay analysis demonstrated that
many of these were regulated post-transcriptionally by hyperosmolarity
in HAC. Analysis of miRNA levels in HAC indicated that they are only
modestly regulated by hyperosmotic conditions, whilst inhibitor studies
showed that p38 MAPK and ERK1/2 were able to block hyperosmotic induction
of many of these genes. Conclusion Through microarray and bioinformatics
analysis we have identified genes which are post-transcriptionally
regulated in HAC following exposure to hyperosmotic conditions. These
genes have a range of functions, and their regulation involves transduction
through the p38 MAPK and ERK1/2 pathways. Interestingly, our results
suggest that miRNA regulation is not key to the process. Overall,
this work illustrates the range of processes regulated in chondrocytes
by changes in their osmotic environment, and underlines the importance
of post-transcriptional mRNA regulation to chondrocyte function.},
doi = {10.1016/j.joca.2011.04.015},
issn = {1063-4584},
keywords = {Chondrocyte},
url = {http://www.sciencedirect.com/science/article/pii/S1063458411001324}
}
@ARTICLE{Tewari2005,
author = {Tewari, Devansu and Monk, Bradley J. and Al-Ghazi, Muthana S. and
Parker, Ricardo and Heck, J. Denis and Burger, Robert A. and Fruehauf,
John P.},
title = {Gene expression profiling of in vitro radiation resistance in cervical
carcinoma: A feasibility study},
journal = {Gynecologic Oncology},
year = {2005},
volume = {99},
pages = {84--91},
number = {1},
month = oct,
abstract = {Objective(s). To determine the feasibility of integrating an in vitro
chemo-radiation response assay (IVRRA) with a gene microarray system
to investigate the molecular patterns of expression that contribute
to radiation resistance in cervical cancer.Methods. Viable primary
untreated cervical cancer specimens were obtained and exposed to
gamma irradiation at a dose of 3 Gy in the IVRRA to determine in
vitro radiation sensitivity. RNA was purified for microarray analysis
with the Affymetrix Human Genome U95A Array carrying more than 12,000
gene probes. Gene expression analysis was performed, and specimen
transcript patterns were correlated with radiation response using
an iteration analysis model and Pearson's correlation coefficient.Results.
A feasibility set of eight tumor specimens was studied. Tumors were
classified into 4 extreme (ERR), 2 intermediate (IRR) and 2 low radiation
resistance (LRR) categories. An intrinsic radiation response gene
set of 54 genes transcripts with 100% accuracy for the classification
of each tumor's radiation response category was identified.Conclusion(s).
Gene sets associated with in vitro radiation response profiles in
cervical cancer can be generated using the IVRRA and microarray technology.
This has direct applications to the study of the biological pathways
contributing to radiation resistance and may lead to the development
of alternative treatment modalities. The potential of these technologies
for cancers in which radiotherapy is employed warrants further investigation.},
issn = {0090-8258},
keywords = {Gene expression profiling, Radiation resistance, Cervical carcinoma},
url = {http://www.sciencedirect.com/science/article/B6WG6-4GX0C2D-1/2/4e7ca5c7495e2e6b9ba5a4e7a7626096}
}
@ARTICLE{Tfelt-Hansen2005,
author = {Tfelt-Hansen, Jacob and Ferreira, Ana and Yano, Shozo and Kanuparthi,
Deephti and Romero, Jose R. and Brown, Edward M. and Chattopadhyay,
Naibedya},
title = {Calcium-sensing receptor activation induces nitric oxide production
in H-500 Leydig cancer cells},
journal = {Am J Physiol Endocrinol Metab},
year = {2005},
volume = {288},
pages = {E1206--1213},
number = {6},
month = jun,
abstract = {Nitric oxide (NO) is a versatile second messenger. NO is produced
by Leydig cells, where NO is a negative regulator of steroidogenesis.
In cancer cells, NO is thought to have mutagenic and proliferative
effects. We have previously shown that the calcium-sensing receptor
(CaR) has promalignant effects in rat H-500 Leydig cancer cells,
a model for humoral hypercalcemia of malignancy. Calcium, the major
physiological ligand of the CaR, is a recognized intracellular cofactor
in the process of NO production by virtue of its positive modulation
of neuronal and endothelial nitric oxide synthase (NOS), but importantly,
not of inducible (i) NOS activity. iNOS activity is regulated by
changes in its expression level. Therefore, we investigated whether
CaR activation changes iNOS expression. We found that high extracellular
calcium (Ca[IMG]f1.gif" BORDER="0">) upregulates the level of mRNA
for iNOS, whereas no change was seen in neuronal or endothelial NOS,
as assessed by microarray and real-time PCR, respectively. The high
Ca[IMG]f1.gif" BORDER="0">-induced iNOS upregulation was also detected
by Northern and Western blotting. By quantitative real-time PCR,
we showed that calcium maximally upregulates iNOS at 18 h. The effect
of calcium was abolished by overexpression of a dominant-negative
CaR (R185Q), confirming that the effect of Ca[IMG]f1.gif" BORDER="0">
was mediated by the CaR. Cells treated with high calcium had higher
NO production than those treated with low calcium, as detected with
the NO-specific DAF2-AM dye. This was confirmed in single-cell fluorescence
determinations using confocal microscopy. In conclusion, high calcium
upregulates the levels of iNOS mRNA and protein as well as NO production
in H-500 cells, and the effect of Ca[IMG]f1.gif" BORDER="0"> on iNOS
expression is mediated by the CaR.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/288/6/E1206}
}
@ARTICLE{Thach2003,
author = {Thach, Dzung C. and Lin, Baochuan and Walter, Elizabeth and Kruzelock,
Rusty and Rowley, Robb K. and Tibbetts, Clark and Stenger, David
A.},
title = {Assessment of two methods for handling blood in collection tubes
with RNA stabilizing agent for surveillance of gene expression profiles
with high density microarrays},
journal = {Journal of Immunological Methods},
year = {2003},
volume = {283},
pages = {269--279},
number = {1-2},
month = dec,
abstract = {Genome-wide expression studies of human blood samples in the context
of epidemiologic surveillance are confronted by numerous challenges--one
of the foremost being the capability to produce reliable detection
of transcript levels. This led us to consider the Paxgene(TM) Blood
RNA System, which consists of a stabilizing additive in an evacuated
blood collection tube (PAX tube) and a sample processing kit (PAX
kit). The PAX tube contains a solution that inhibits RNA degradation
and gene induction as blood is drawn into the tube. The stability
of RNA in PAX tubes under conditions for practical clinical applications
has been determined by RT-PCR (Clin. Chem. 48 (2002) 1883), but has
not been assessed at the transcriptome level on Affymetrix® microarrays.
Here, we report a quality assured and controlled protocol that is
capable of producing reliable gene expression profiles using the
GeneChip® system with RNA isolated from PAX tubes. Using this protocol,
we compared quality metrics and gene-expression profiles of RNA,
extracted from blood in PAX tubes that sat at room temperature for
2 h, with that of blood in PAX tubes incubated at room temperature
for 9 h followed by storage at -20 °C for 6 days. Of numerous metrics,
differences between the two handling methods were detected for the
level of DNA contamination, RNA yield, and double stranded cDNA yield.
Analysis of variance of gene-expression revealed small but significant
differences between the handling methods. These results contribute
to the determination of protocols for clinical studies and progress
us towards the goal of using the transcriptome in diagnosis and surveillance.},
issn = {0022-1759},
keywords = {Gene expression, Paxgene RNA tube, Fresh versus frozen},
url = {http://www.sciencedirect.com/science/article/B6T2Y-49YD2B9-9/2/2f8c15a86796df59dd09417798ec425a}
}
@ARTICLE{Thacker2009,
author = {Thacker, Michael A. and Clark, Anna K. and Bishop, Thomas and Grist,
John and Yip, Ping K. and Moon, Lawrence D.F. and Thompson, Stephen
W.N. and Marchand, Fabien and McMahon, Stephen B.},
title = {CCL2 is a key mediator of microglia activation in neuropathic pain
states},
journal = {European Journal of Pain},
year = {2009},
volume = {13},
pages = {263--272},
number = {3},
month = mar,
abstract = {While neuroimmune interactions are increasingly recognized as important
in nociceptive processing, the nature and functional significance
of these interactions is not well defined. There are multiple reports
that the activation of spinal microglia is a critical event in the
generation of neuropathic pain behaviors but the mediators of this
activation remain disputed. Here we show that the chemokine CCL2,
produced by both damaged and undamaged primary sensory neurons in
neuropathic pain states in rats, is released in an activity dependent
manner from the central terminals of these fibres. We also demonstrate
that intraspinal CCL2 in naïve rats leads to activation of spinal
microglia and neuropathic pain-like behavior. An essential role for
spinal CCL2 is demonstrated by the inhibition of neuropathic pain
behavior and microglial activation by a specific neutralising antibody
to CCL2 administered intrathecally. Thus, the neuronal expression
of CCL2 provides a mechanism for immune activation, which in turn
regulates the sensitivity of pain signaling systems in neuropathic
pain states.},
issn = {1090-3801},
keywords = {CCL2, Microglia, Neuropathic pain, Rat},
url = {http://www.sciencedirect.com/science/article/B6WF3-4SRDFK2-2/2/b152c421ed196416d421f78536de8d35}
}
@ARTICLE{Thacker2010,
author = {Thacker, Seth G. and Berthier, Celine C. and Mattinzoli, Deborah
and Rastaldi, Maria Pia and Kretzler, Matthias and Kaplan, Mariana
J.},
title = {The Detrimental Effects of IFN-{alpha} on Vasculogenesis in Lupus
Are Mediated by Repression of IL-1 Pathways: Potential Role in Atherogenesis
and Renal Vascular Rarefaction},
journal = {J. Immunol.},
year = {2010},
volume = {185},
pages = {4457--4469},
number = {7},
month = oct,
abstract = {Systemic lupus erythematosus (SLE) is characterized by increased vascular
risk due to premature atherosclerosis independent of traditional
risk factors. We previously proposed that IFN-{alpha} plays a crucial
role in premature vascular damage in SLE. IFN-{alpha} alters the
balance between endothelial cell apoptosis and vascular repair mediated
by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic
cells (CACs). In this study, we demonstrate that IFN-{alpha} promotes
an antiangiogenic signature in SLE and control EPCs/CACs, characterized
by transcriptional repression of IL-1{alpha} and {beta}, IL-1R1,
and vascular endothelial growth factor A, and upregulation of IL-1R
antagonist and the decoy receptor IL-1R2. IL-1{beta} promotes significant
improvement in the functional capacity of lupus EPCs/CACs, therefore
abrogating the deleterious effects of IFN-{alpha}. The beneficial
effects from IL-1 are mediated, at least in part, by increases in
EPC/CAC proliferation, by decreases in EPC/CAC apoptosis, and by
preventing the skewing of CACs toward nonangiogenic pathways. IFN-{alpha}
induces STAT2 and 6 phosphorylation in EPCs/CACs, and JAK inhibition
abrogates the transcriptional antiangiogenic changes induced by IFN-{alpha}
in these cells. Immunohistochemistry of renal biopsies from patients
with lupus nephritis, but not anti-neutrophil cytoplasmic Ab-positive
vasculitis, showed this pathway to be operational in vivo, with increased
IL-1R antagonist, downregulation of vascular endothelial growth factor
A, and glomerular and blood vessel decreased capillary density, compared
with controls. Our study introduces a novel putative pathway by which
type I IFNs may interfere with vascular repair in SLE through repression
of IL-1-dependent pathways. This could promote atherosclerosis and
loss of renal function in this disease.},
url = {http://www.jimmunol.org/cgi/content/abstract/185/7/4457}
}
@ARTICLE{Thaisuchat2011,
author = {Thaisuchat, Haruthai and Baumann, Martina and Pontiller, Jens and
Hesse, Friedemann and Ernst, Wolfgang},
title = {Identification of a Novel Temperature Sensitive Promoter in CHO cells},
journal = {BMC Biotechnology},
year = {2011},
volume = {11},
pages = {51},
number = {1},
abstract = {BACKGROUND:The Chinese hamster ovary (CHO) expression system is the
leading production platform for manufacturing biopharmaceuticals
for the treatment of numerous human diseases. Efforts to optimize
the production process also include the genetic construct encoding
the therapeutic gene. Here we report about the successful identification
of an endogenous highly active gene promoter obtained from CHO cells
which shows conditionally inducible gene expression at reduced temperature.
RESULTS:Based on CHO microarray expression data abundantly transcribed
genes were selected as potential promoter candidates. The S100a6
(calcyclin) and its flanking regions were identified from a genomic
CHO-K1 lambda-phage library. Computational analyses showed a predicted
TSS, a TATA-box and several TFBSs within the 1.5 kb region upstream
the ATG start signal. Various constructs were investigated for promoter
activity at 37degreesC and 33degreesC in transient luciferase reporter
gene assays. Most constructs showed expression levels even higher
than the SV40 control and on average a more than two-fold increase
at lower temperature. We identified the core promoter sequence (222
bp) comprising two SP1 sites and could show a further increase in
activity by duplication of this minimal sequence. CONCLUSIONS:This
novel CHO promoter permits conditionally high-level gene expression.
Upon a shift to 33degreesC, a two to three-fold increase of basal
productivity (already higher than SV40 promoter) is achieved. This
property is of particular advantage for a process with reduced expression
during initial cell growth followed by the production phase at low
temperature with a boost in expression. Additionally, production
of toxic proteins becomes feasible, since cell metabolism and gene
expression do not directly interfere. The CHO S100a6 promoter can
be characterized as cold-shock responsive with the potential for
improving process performance of mammalian expression systems. },
doi = {10.1186/1472-6750-11-51},
issn = {1472-6750},
pubmedid = {21569433},
url = {http://www.biomedcentral.com/1472-6750/11/51}
}
@ARTICLE{Thakur2009,
author = {Thakur, Sheetal A. and Beamer, Celine A. and Migliaccio, Christopher
T. and Holian, Andrij},
title = {Critical Role of MARCO in Crystalline Silica-Induced Pulmonary Inflammation},
journal = {Toxicol. Sci.},
year = {2009},
volume = {108},
pages = {462--471},
number = {2},
month = apr,
abstract = {Chronic exposure to crystalline silica can lead to the development
of silicosis, an irreversible, inflammatory and fibrotic pulmonary
disease. Although, previous studies established the macrophage receptor
with collagenous structure (MARCO) as an important receptor for binding
and uptake of crystalline silica particles in vitro, the role of
MARCO in regulating the inflammatory response following silica exposure
in vivo remains unknown. Therefore, we determined the role of MARCO
in crystalline silica-induced pulmonary pathology using C57Bl/6 wild-type
(WT) and MARCO-/- mice. Increased numbers of MARCO+ pulmonary macrophages
were observed following crystalline silica, but not phosphate-buffered
saline and titanium dioxide (TiO2), instillation in WT mice, highlighting
a specific role of MARCO in silica-induced pathology. We hypothesized
that MARCO-/- mice will exhibit diminished clearance of silica leading
to enhanced pulmonary inflammation and exacerbation of silicosis.
Alveolar macrophages isolated from crystalline silica-exposed mice
showed diminished particle uptake in vivo as compared with WT mice,
indicating abnormalities in clearance mechanisms. Furthermore, MARCO-/-
mice exposed to crystalline silica showed enhanced acute inflammation
and lung injury marked by increases in early response cytokines and
inflammatory cells compared with WT mice. Similarly, histological
examination of MARCO-/- lungs at 3 months post-crystalline silica
exposure showed increased chronic inflammation compared with WT;
however, only a small difference was observed with respect to development
of fibrosis as measured by hydroxyproline content. Altogether, these
results demonstrate that MARCO is important for clearance of crystalline
silica in vivo and that the absence of MARCO results in exacerbations
in innate pulmonary immune responses.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/108/2/462}
}
@ARTICLE{Thalacker-Mercer2010,
author = {Thalacker-Mercer, Anna E. and Dell'Italia, Louis J. and Cui, Xiangqin
and Cross, James M. and Bamman, Marcas M.},
title = {Differential genomic responses in old vs. young humans despite similar
levels of modest muscle damage after resistance loading},
journal = {Physiol Genomics},
year = {2010},
volume = {40},
pages = {141--149},
number = {3},
month = feb,
abstract = {Across numerous model systems, aging skeletal muscle demonstrates
an impaired regenerative response when exposed to the same stimulus
as young muscle. To better understand the impact of aging in a human
model, we compared changes to the skeletal muscle transcriptome induced
by unaccustomed high-intensity resistance loading (RL) sufficient
to cause moderate muscle damage in young (37 yr) vs. older (73 yr)
adults. Serum creatine kinase was elevated 46% 24 h after RL in all
subjects with no age differences, indicating similar degrees of myofiber
membrane wounding by age. Despite this similarity, from genomic microarrays
318 unique transcripts were differentially expressed after RL in
old vs. only 87 in young subjects. Follow-up pathways analysis and
functional annotation revealed among old subjects upregulation of
transcripts related to stress and cellular compromise, inflammation
and immune responses, necrosis, and protein degradation and changes
in expression (up- and downregulation) of transcripts related to
skeletal and muscular development, cell growth and proliferation,
protein synthesis, fibrosis and connective tissue function, myoblast-myotube
fusion and cell-cell adhesion, and structural integrity. Overall
the transcript-level changes indicative of undue inflammatory and
stress responses in these older adults were not mirrored in young
subjects. Follow-up immunoblotting revealed higher protein expression
among old subjects for NF-{kappa}B, heat shock protein (HSP)70, and
IL-6 signaling [total and phosphorylated signal transducer and activator
of transcription (STAT)3 at Tyr705]. Together, these novel findings
suggest that young and old adults are equally susceptible to RL-mediated
damage, yet the muscles of older adults are much more sensitive to
this modest degree of damage--launching a robust transcriptome-level
response that may begin to reveal key differences in the regenerative
capacity of skeletal muscle with advancing age.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/40/3/141}
}
@ARTICLE{Thamatrakoln2012,
author = {Thamatrakoln, Kimberlee and Korenovska, Olga and Niheu, A. Kalani
and Bidle, Kay D.},
title = {Whole-genome expression analysis reveals a role for death-related
genes in stress acclimation of the diatom Thalassiosira pseudonana},
journal = {Environmental Microbiology},
year = {2012},
volume = {14},
pages = {67--81},
number = {1},
abstract = {Low iron (Fe) availability critically limits diatom distribution and
productivity in vast regions of the modern ocean, such as open-ocean,
high nutrient low chlorophyll areas and coastal regimes characterized
as Fe limitation ‘mosaics’. While unique strategies of Fe uptake
and storage confer competitive advantages to pennate diatoms, the
molecular determinants of low Fe acclimation are largely unknown
in centric diatoms. We combined genome-wide and targeted comparative
transcriptomic analysis with diagnostic biochemistry and in vivo
cell staining as a platform to identify the suite of genes involved
in acclimation to Fe and associated oxidative stress in Thalassiosira
pseudonana. A total of 1312 genes, nearly 12% of the total genome
content, responded to Fe starvation in growing cells characterized
by low photosynthetic efficiency and enhanced oxidative stress, caspase
activity and metacaspase expression. While 82% of the most highly
upregulated genes were also represented in EST libraries derived
from diverse diatoms grown under various stress conditions (e.g.
silicon, CO2 and nitrogen limitation), our analysis suggests that
T. pseudonana mounts a unique molecular response to Fe starvation
that includes a number of genes distinct from those of the model
pennate diatom, Phaeodactylum tricornutum, which diverged ∼90 million
years ago. Homologues to ∼50% of the upregulated genes were also
identified in a metatranscriptome of eukaryotic phytoplankton communities
from a chronically Fe-limited region in the Northeast Pacific. Furthermore,
we provide experimental evidence that a subset of putative death-related
genes participate in the cellular acclimation to low Fe and associated
oxidative damage, suggesting that they co-evolved with other metabolic
pathways and play adaptive roles in the success of diatoms.},
doi = {10.1111/j.1462-2920.2011.02468.x},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2011.02468.x}
}
@ARTICLE{Thambisetty2010,
author = {Thambisetty, Madhav and Simmons, Andrew and Velayudhan, Latha and
Hye, Abdul and Campbell, James and Zhang, Yi and Wahlund, Lars-Olof
and Westman, Eric and Kinsey, Anna and Guntert, Andreas and Proitsi,
Petroula and Powell, John and Causevic, Mirsada and Killick, Richard
and Lunnon, Katie and Lynham, Steven and Broadstock, Martin and Choudhry,
Fahd and Howlett, David R. and Williams, Robert J. and Sharp, Sally
I. and Mitchelmore, Cathy and Tunnard, Catherine and Leung, Rufina
and Foy, Catherine and O'Brien, Darragh and Breen, Gerome and Furney,
Simon J. and Ward, Malcolm and Kloszewska, Iwona and Mecocci, Patrizia
and Soininen, Hilkka and Tsolaki, Magda and Vellas, Bruno and Hodges,
Angela and Murphy, Declan G. M. and Parkins, Sue and Richardson,
Jill C. and Resnick, Susan M. and Ferrucci, Luigi and Wong, Dean
F. and Zhou, Yun and Muehlboeck, Sebastian and Evans, Alan and Francis,
Paul T. and Spenger, Christian and Lovestone, Simon},
title = {Association of Plasma Clusterin Concentration With Severity, Pathology,
and Progression in Alzheimer Disease},
journal = {Arch Gen Psychiatry},
year = {2010},
volume = {67},
pages = {739--748},
number = {7},
month = jul,
abstract = {Context Blood-based analytes may be indicators of pathological processes
in Alzheimer disease (AD). Objective To identify plasma proteins
associated with AD pathology using a combined proteomic and neuroimaging
approach. Design Discovery-phase proteomics to identify plasma proteins
associated with correlates of AD pathology. Confirmation and validation
using immunodetection in a replication set and an animal model. Setting
A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal
Study of Aging. Participants Patients with AD, subjects with mild
cognitive impairment, and healthy controls with standardized clinical
assessments and structural neuroimaging. Main Outcome Measures Association
of plasma proteins with brain atrophy, disease severity, and rate
of clinical progression. Extension studies in humans and transgenic
mice tested the association between plasma proteins and brain amyloid.
Results Clusterin/apolipoprotein J was associated with atrophy of
the entorhinal cortex, baseline disease severity, and rapid clinical
progression in AD. Increased plasma concentration of clusterin was
predictive of greater fibrillar amyloid-{beta} burden in the medial
temporal lobe. Subjects with AD had increased clusterin messenger
RNA in blood, but there was no effect of single-nucleotide polymorphisms
in the gene encoding clusterin with gene or protein expression. APP/PS1
transgenic mice showed increased plasma clusterin, age-dependent
increase in brain clusterin, as well as amyloid and clusterin colocalization
in plaques. Conclusions These results demonstrate an important role
of clusterin in the pathogenesis of AD and suggest that alterations
in amyloid chaperone proteins may be a biologically relevant peripheral
signature of AD.},
url = {http://archpsyc.ama-assn.org/cgi/content/abstract/67/7/739}
}
@ARTICLE{Than2008,
author = {Than, Nandor Gabor and Kim, Sung-Su and Abbas, Asad and Han, Yu Mi
and Hotra, John and Tarca, Adi L. and Erez, Offer and Wildman, Derek
E. and Kusanovic, Juan Pedro and Pineles, Beth and Montenegro, Daniel
and Edwin, Samuel S. and Mazaki-Tovi, Shali and Gotsch, Francesca
and Espinoza, Jimmy and Hassan, Sonia S. and Papp, Zoltan and Romero,
Roberto},
title = {ORIGINAL ARTICLE: Chorioamnionitis and Increased Galectin-1 Expression
in PPROM – An Anti-Inflammatory Response in the Fetal Membranes?},
journal = {American Journal of Reproductive Immunology},
year = {2008},
volume = {60},
pages = {298--311},
number = {4},
abstract = {Problem Galectin-1 can regulate immune responses upon infection and
inflammation. We determined galectin-1 expression in the chorioamniotic
membranes and its changes during histological chorioamnionitis. Method
of study Chorioamniotic membranes were obtained from women with normal
pregnancy (n = 5) and from patients with pre-term pre-labor rupture
of the membranes (PPROM) with (n = 8) and without histological
chorioamnionitis (n = 8). Galectin-1 mRNA and protein were localized
by in situ hybridization and immunohistochemistry. Galectin-1 mRNA
expression was also determined by quantitative reverse transcriptase
polymerase chain reaction. Results Galectin-1 mRNA and protein were
detected in the amniotic epithelium, chorioamniotic fibroblasts/myofibroblasts
and macrophages, chorionic trophoblasts, and decidual stromal cells.
In patients with PPROM, galectin-1 mRNA expression in the fetal membranes
was higher (2.07-fold, P = 0.002) in those with chorioamnionitis
than in those without. Moreover, chorioamionitis was associated with
a strong galectin-1 immunostaining in amniotic epithelium, chorioamniotic
mesodermal cells, and apoptotic bodies. Conclusion Chorioamnionitis
is associated with an increased galectin-1 mRNA expression and strong
immunoreactivity of the chorioamniotic membranes; thus, galectin-1
may be involved in the regulation of the inflammatory responses to
chorioamniotic infection.},
issn = {1600-0897},
keywords = {Chorioamniotic fibroblast/myofibroblast and macrophage, chorioamniotic
membranes, inflammation, lectin, pre-labor rupture of membranes,
pre-term delivery},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0897.2008.00624.x}
}
@ARTICLE{Than2008a,
author = {Than, Nandor Gabor and Romero, Roberto and Erez, Offer and Weckle,
Amy and Tarca, Adi L. and Hotra, John and Abbas, Asad and Han, Yu
Mi and Kim, Sung-Su and Kusanovic, Juan Pedro and Gotsch, Francesca
and Hou, Zhuocheng and Santolaya-Forgas, Joaquin and Benirschke,
Kurt and Papp, Zoltan and Grossman, Lawrence I. and Goodman, Morris
and Wildman, Derek E.},
title = {Emergence of hormonal and redox regulation of galectin-1 in placental
mammals: Implication in maternal-fetal immune tolerance},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {15819--15824},
number = {41},
month = oct,
abstract = {Galectin-1 is an anti-inflammatory lectin with pleiotropic regulatory
functions at the crossroads of innate and adaptive immunity. It is
expressed in immune privileged sites and is implicated in establishing
maternal-fetal immune tolerance, which is essential for successful
pregnancy in eutherian mammals. Here, we show conserved placental
localization of galectin-1 in primates and its predominant expression
in maternal decidua. Phylogenetic footprinting and shadowing unveil
conserved cis motifs, including an estrogen responsive element in
the 5' promoter of LGALS1, that were gained during the emergence
of placental mammals and could account for sex steroid regulation
of LGALS1 expression, thus providing additional evidence for the
role of galectin-1 in immune-endocrine cross-talk. Maximum parsimony
and maximum likelihood analyses of 27 publicly available vertebrate
and seven newly sequenced primate LGALS1 coding sequences reveal
that intense purifying selection has been acting on residues in the
carbohydrate recognition domain and dimerization interface that are
involved in immune functions. Parsimony- and codon model-based phylogenetic
analysis of coding sequences show that amino acid replacements occurred
in early mammalian evolution on key residues, including gain of cysteines,
which regulate immune functions by redox status-mediated conformational
changes that disable sugar binding and dimerization, and that the
acquired immunoregulatory functions of galectin-1 then became highly
conserved in eutherian lineages, suggesting the emergence of hormonal
and redox regulation of galectin-1 in placental mammals may be implicated
in maternal-fetal immune tolerance.},
url = {http://www.pnas.org/cgi/content/abstract/105/41/15819}
}
@ARTICLE{Thasler2005,
author = {Thasler, W E and Schlott, T and Thelen, P and Hellerbrand, C and
Bataille, F and Lichtenauer, M and Schlitt, H-J and Jauch, K-W and
Weiss, T S},
title = {Expression of augmenter of liver regeneration (ALR) in human liver
cirrhosis and carcinoma},
journal = {Histopathology},
year = {2005},
volume = {47},
pages = {57--66},
number = {1},
abstract = {Aims : To determine the expression of a protein termed augmenter
of liver regeneration (ALR), recently found to have a specific and
beneficial effect on the process of liver regeneration in normal
and diseased human liver. Methods and results : ALR expression
in normal and cirrhotic human livers with various underlying diseases
as well as in tissue samples of hepatocellular carcinoma (HCC) and
cholangiocellular carcinoma (CCC) was analysed by immunohistochemistry
and quantitative reverse transciptase-polymerase chain reaction (RT-PCR).
Expression analysis of ALR in total liver protein extracts by Western
blotting showed mainly dimeric ALR protein. Immunohistochemically,
cytosolic and perinuclear immunosignals were found in hepatocytes
and cholangiocytes in normal, cirrhotic or cancerous liver tissue
and only weak signals in some endothelial cells in normal livers.
Quantitative mRNA analysis revealed significantly increased ALR expression
in cirrhosis compared with normal liver tissue. In HCC and CCC ALR
mRNA expression was also significantly enhanced compared with normal
liver tissue, but expression levels did not differ from the matching
non-neoplastic tissue in the same patient. Conclusions : The findings
suggest an important role for ALR in hepatocellular regeneration
in liver cirrhosis as well as in hepatocarcinogenesis and therefore
its potential value in the clinical diagnosis of hepatic cirrhosis
and cancer.},
issn = {1365-2559},
keywords = {augmenter of liver regeneration, immunohistochemistry, liver carcinoma,
liver cirrhosis, real-time RT-PCR},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2559.2005.02172.x}
}
@ARTICLE{Thedrez2009,
author = {Thedrez, Aurelie and Harly, Christelle and Morice, Alexis and Salot,
Samuel and Bonneville, Marc and Scotet, Emmanuel},
title = {IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory
Responses of Human V{gamma}9V{delta}2 T Cells for Adoptive Immunotherapy},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {3423--3431},
number = {6},
month = mar,
abstract = {V{gamma}9V{delta}2 T lymphocytes are a major human {gamma}{delta}
T cell subset that react against a wide array of tumor cells, through
recognition of phosphorylated isoprenoid pathway metabolites called
phosphoantigens. Immunotherapeutic protocols targeting V{gamma}9V{delta}2
T cells have yielded promising, yet limited, signs of antitumor efficacy.
To improve these approaches, we analyzed the effects on {gamma}{delta}
T cells of IL-21, a cytokine known to enhance proliferation and effector
functions of CD8+ T cells and NK cells. IL-21 induced limited division
of phosphoantigen-stimulated V{gamma}9V{delta}2 T cells, but did
not modulate their sustained expansion induced by exogenous IL-2.
V{gamma}9V{delta}2 T cells expanded in the presence of IL-21 and
IL-2 showed enhanced antitumor cytolytic responses, associated with
increased expression of CD56 and several lytic molecules, and increased
tumor-induced degranulation capacity. IL-21 plus IL-2-expanded V{gamma}9V{delta}2
T cells expressed higher levels of inhibitory receptors (e.g., ILT2
and NKG2A) and lower levels of the costimulatory molecule NKG2D.
Importantly, these changes were rapidly and reversibly induced after
short-term culture with IL-21. Finally, IL-21 irreversibly enhanced
the proinflammatory Th1 polarization of expanded V{gamma}9V{delta}2
T cells when added at the beginning of the culture. These data suggest
a new role played by IL-21 in the cytotoxic and Th1 programming of
precommitted Ag-stimulated {gamma}{delta} T cells. On a more applied
standpoint, IL-21 could be combined to IL-2 to enhance {gamma}{delta}
T cell-mediated antitumor responses, and thus represents a promising
way to optimize immunotherapies targeting this cell subset.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/6/3423}
}
@ARTICLE{Thelen2007,
author = {Thelen, Paul and Peter, Thomas and Hünermund, Anika and Kaulfuß,
Silke and Seidlová-Wuttke, Dana and Wuttke, Wolfgang and Ringert,
Rolf-Hermann and Seseke, Florian},
title = {Phytoestrogens from Belamcanda chinensis regulate the expression
of steroid receptors and related cofactors in LNCaP prostate cancer
cells},
journal = {BJU International},
year = {2007},
volume = {100},
pages = {199--203},
number = {1},
abstract = {OBJECTIVE To investigate the changes in expression underlying the
marked reduction of tumour growth in vivo, by analysing the effect
of Belamcanda chinensis extract (BCE) on LNCaP cells in vitro, as
phytoestrogens are chemopreventive in prostate cancer, and in previous
studies we examined the effects of the isoflavone tectorigenin isolated
from B. chinensis on LNCaP prostate cancer cells, and a BCE consisting
of 13 phytoestrogenic compounds on tumour-bearing nude mice. MATERIALS
AND METHODS LNCaP cells were treated with 100, 400 or 1400 µg/mL
BCE; proliferation was assessed with an Alamar Blue assay. We used
real-time reverse transcription-polymerase chain reaction to quantify
mRNA expression of the androgen receptor (AR), the AR coactivator
prostate derived Ets transcription factor (PDEF), NKX3.1, prostate
specific antigen (PSA) and oestrogen receptor-β (ER-β) compared
with the expression of the housekeeping gene porphobilinogen deaminase
(PBGD). PSA secretion from LNCaP cells was measured and protein expression
of the AR investigated by Western blot analysis. RESULTS Concomitant
with a marked decrease of tumour cell proliferation BCE down-regulated
the expression of the AR, PDEF, NKX3.1 and PSA. In the same experiments,
the expression of PBGD was unaltered, whereas ER-β expression increased.
Furthermore, AR protein and PSA secretion were markedly diminished
after treatments with the BCE. CONCLUSION BCE, comprising 13 different
phytoestrogens, decreases the expression of the AR and its co-activator
PDEF concomitant with diminished cell proliferation and PSA secretion.
NKX3.1 expression was also reduced by BCE. We hypothesise that the
positive effects of BCE are initiated by up-regulation of the ER-β,
a putative tumour-suppressor gene.},
issn = {1464-410X},
keywords = {prostate cancer, LNCaP, phytoestrogens, androgen receptor, oestrogen,
proliferation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-410X.2007.06924.x}
}
@ARTICLE{Thelen2005,
author = {Thelen, Paul and Scharf, Jens-Gerd and Burfeind, Peter and Hemmerlein,
Bernhard and Wuttke, Wolfgang and Spengler, Barbara and Christoffel,
Volker and Ringert, Rolf-Hermann and Seidlova-Wuttke, Dana},
title = {Tectorigenin and other phytochemicals extracted from leopard lily
Belamcanda chinensis affect new and established targets for therapies
in prostate cancer},
journal = {Carcinogenesis},
year = {2005},
volume = {26},
pages = {1360--1367},
number = {8},
month = aug,
abstract = {Isoflavones have been shown to exert antiproliferative effects on
cancer cells by steroid receptor signaling. In this study, we demonstrate
the potential of plant constituents extracted from Belamcanda chinensis
as anticancer drugs, which regulate the aberrant expression of genes
relevant in proliferation, invasion, immortalization and apoptosis.
LNCaP cells were treated with B.chinensis extract, tectorigenin or
other isoflavones and mRNA expression was quantified by using real
time RT-PCR. In addition, ELISA, TRAP assays and western blots were
used to measure protein expression or activity. Male nude mice (n
= 18) were injected subcutaneously with LNCaP cells and were fed
with extracts from B.chinensis, and tumor development was monitored
versus a control animal group (n = 18). Tectorigenin and several
other phytochemicals downregulated PDEF, PSA and IGF-1 receptor mRNA
expression in vitro. Furthermore, PSA secretion and IGF-1 receptor
protein expression were diminished, and hTERT mRNA expression and
telomerase activity decreased after tectorigenin treatments. However,
TIMP-3 mRNA was upregulated on tectorigenin treatment. Growth of
subcutaneous tumors in nude mice was delayed and diminished in animals
fed with extracts from B.chinensis. The downregulation of PDEF, PSA,
hTERT and IGF-1 receptor gene expression by tectorigenin demonstrates
the antiproliferative potential of these agents. The upregulation
of TIMP-3 gene expression indicates a pro-apoptotic function of the
drug and a reduction of the invasiveness of tumors. The animal experiments
demonstrate that B.chinensis markedly inhibited the development of
tumors in vivo. Thus, these compounds may be useful for the prevention
or treatment of human prostate cancer.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/26/8/1360}
}
@ARTICLE{THELEN2004,
author = {THELEN, P. and WUTTKE, W. and JARRY, H. and GRZMIL, M. and RINGERT,
R.-H.},
title = {Inhibition of Telomerase Activity and Secretion of Prostate Specific
Antigen by Silibinin in Prostate Cancer Cells},
journal = {The Journal of Urology},
year = {2004},
volume = {171},
pages = {1934--1938},
number = {5},
month = may,
abstract = {ABSTRACTPurpose The androgen sensitive prostate cancer cell line LNCaP
is strongly positive for dihydrotestosterone (DHT) dependent telomerase
activity, which is an important factor in cellular immortality and
carcinogenesis. In this study we determined the potential of silibinin
as an anticancer drug that down-regulates telomerase activity and
prostate specific antigen (PSA) together with the co-activator of
the androgen receptor prostate epithelium specific Ets transcription
factor.Materials and Methods LNCaP cells were treated with various
concentrations of silibinin in the presence or absence of 5[alpha]-DHT.
We used real-time reverse transcriptase-polymerase chain reaction
to quantify mRNA expression of PSA, prostate epithelium specific
Ets transcription factor and the catalytic subunit of telomerase
vs the housekeeping gene porphobilinogen deaminase with gene specific,
dual labeled fluorescence probes. PSA secretion from LNCaP cells
in conditioned medium was measured with an Elecsys System 2010 (Roche
Diagnostics, Mannheim, Germany) and telomerase activity in extracts
from LNCaP cells was measured with a TRAP (telomeric repeat amplification
protocol) assay.Results Silibinin down-regulated PSA mRNA expression
and PSA secretion in conditioned medium. Simultaneous stimulation
with silibinin and 10-8 M DHT also resulted in PSA down-regulation,
whereas DHT alone increased PSA secretion. Telomerase catalytic subunit
mRNA decreased significantly after silibinin stimulation. Telomerase
activity was down-regulated by silibinin and stimulated by DHT. The
2 agents in combination resulted in telomerase down-regulation.Conclusions
The down-regulation of PSA by silibinin and its counteraction on
DHT effects indicate that this compound can interact with the expression
of genes that are regulated through the androgen receptor. Silibinin
can also inhibit the telomerase activity that mediates cell immortality
and carcinogenesis. The 2 effects underline the possible therapeutic
use of silibinin as an antiproliferative agent in intervention for
prostate cancer.},
issn = {0022-5347},
keywords = {prostate, prostate-specific antigen, telomerase, prostatic neoplasms},
url = {http://www.sciencedirect.com/science/article/B7XMT-4HGCK44-1K/2/afcd0ee80083ea88f204ada91c40aceb}
}
@ARTICLE{Thelie2009,
author = {Thelie, Aurore and Papillier, Pascal and Perreau, Christine and Uzbekova,
Svetlana and Hennequet-Antier, Christelle and Dalbies-Tran, Rozenn},
title = {Regulation of bovine oocyte-specific transcripts during in vitro
oocyte maturation and after maternal–embryonic transition analyzed
using a transcriptomic approach},
journal = {Mol. Reprod. Dev.},
year = {2009},
volume = {76},
pages = {773--782},
number = {8},
abstract = {Abstract 10.1002/mrd.21031.abs Oocyte/embryo genomics in mammals faces
specific challenges due to limited biological material, to the comparison
of models with different total RNA contents, and to expression of
a specific set of genes often absent from commercially available
microarrays. Here, we report experimental validation of a RNA amplification
protocol for bovine oocytes and blastocysts. Using real-time PCR,
we have confirmed that the profile of both abundant and scarce polyadenylated
transcripts was conserved after RNA amplification. Next, amplified
probes generated from immature oocytes, in vitro matured oocytes,
and in vitro produced hatched blastocysts were hybridized onto a
macroarray that included oocyte-specific genes. Following an original
approach, we have compared two normalization procedures, based on
the median signal or an exogenous standard. We have evidenced the
expected difference in sets of differential genes depending on the
normalization procedure. Using a 1.5-fold threshold, no transcript
was found to be upregulated when data were normalized to an exogenous
standard, which reflects the absence of transcription during in vitro
oocyte maturation. In blastocysts, the majority of oocyte-preferentially
expressed genes were not activated, as previously observed in mouse.
Finally, microarray data were validated by real-time PCR on a random
subset of genes. Our study sheds new light on and complements previous
transcriptomic analyses of bovine oocyte to embryo transition using
commercial platforms. Mol. Reprod. Dev. 76: 773–782, 2009. © 2009
Wiley-Liss, Inc.},
issn = {1098-2795},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mrd.21031}
}
@ARTICLE{Theunissen2010,
author = {Theunissen, P.T. and Schulpen, S.H.W. and van Dartel, D.A.M. and
Hermsen, S.A.B. and van Schooten, F.J. and Piersma, A.H.},
title = {An abbreviated protocol for multilineage neural differentiation of
murine embryonic stem cells and its perturbation by methyl mercury},
journal = {Reproductive Toxicology},
year = {2010},
volume = {29},
pages = {383--392},
number = {4},
month = jul,
abstract = {Alternative assays are highly desirable to reduce the extensive experimental
animal use in developmental toxicity testing. In the present study,
we developed an improved test system for assessing neurodevelopmental
toxicity using differentiating embryonic stem cells. We advanced
previously established methods by merging, modifying and abbreviating
the original 20-day protocol into a more efficient 13-day neural
differentiation protocol. Using morphological observation, immunocytochemistry,
gene expression and flow cytometry, it was shown predominantly multiple
lineages of neuroectodermal cells were formed in our protocol and
to a lower extent, endodermal and mesodermal differentiated cell
types. This abbreviated protocol should lead to an advanced screening
method using morphology in combination with selected differentiation
markers aimed at predicting neurodevelopmental toxicity. Finally,
the assay was shown to express differential sensitivity to a model
developmental neurotoxicant, methyl mercury.},
issn = {0890-6238},
keywords = {Embryonic stem cells, Developmental toxicity, Alternative test method,
Neural differentiation, Methyl mercury},
url = {http://www.sciencedirect.com/science/article/B6TC0-4YWXSDB-1/2/8eda981801739020dd17fe860e2cae07}
}
@ARTICLE{Theunissen2011,
author = {Theunissen, Peter T. and Pennings, Jeroen L. A. and Robinson, Joshua
F. and Claessen, Sandra M. H. and Kleinjans, Jos C. S. and Piersma,
Aldert H.},
title = {Time-Response Evaluation by Transcriptomics of Methylmercury Effects
on Neural Differentiation of Murine Embryonic Stem Cells},
journal = {Toxicol. Sci.},
year = {2011},
volume = {122},
pages = {437-447},
number = {2},
abstract = {Current globally harmonized Organisation for Economic Co-operation
and Development (OECD) animal test guidelines for developmental toxicity
require high numbers of experimental animals. To reduce animal use
in this field, alternative developmental toxicity assays are highly
desirable. We previously developed a dynamic in vitro model for screening
effects of possible neurodevelopmental toxicants, using neural cell
differentiation of pluripotent murine embryonic stem cells. To further
mechanistically characterize the mouse neural embryonic stem cell
test (ESTn) and to improve detection of possible neurodevelopmental
toxicants, gene expression patterns were studied describing neural
cell differentiation over time, as well as the impact on gene expression
of exposure to the well-known neurotoxicant methylmercury (MeHg).
A transcriptomics study was performed to examine whole-genome expression
changes during the first 7 days of the cell differentiation protocol.
Specific gene clusters were identified and enrichment analysis of
Gene Ontology (GO) terms and gene sets derived from literature was
performed using DAVID and T-profiler. Over time, a decrease of blastocyst
and trophectoderm GO terms was observed, which included well-characterized
pluripotency genes. Furthermore, an increase in the range of neural
development-related GO terms, such as neuron differentiation and
the wnt pathway, was observed. Analysis of gene expression using
principle component analysis showed a time-dependent track in untreated
cells, describing the process of neural differentiation. Furthermore,
MeHg was shown to induce deviation from the predefined differentiation
track. The compound inhibited general development GO terms and induced
neural GO terms over time. This system appears promising for studying
compound effects on neural differentiation in a mechanistic approach.},
doi = {10.1093/toxsci/kfr134},
eprint = {http://toxsci.oxfordjournals.org/cgi/reprint/122/2/437.pdf},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/122/2/437}
}
@ARTICLE{Theuwissen2009,
author = {Theuwissen, Elke and Plat, Jogchum and Mensink, Ronald P.},
title = {Consumption of oat β-glucan with or without plant stanols did not
influence inflammatory markers in hypercholesterolemic subjects},
journal = {Mol. Nutr. Food Res.},
year = {2009},
volume = {53},
pages = {370--376},
number = {3},
abstract = {Abstract 10.1002/mnfr.200800132.abs We have earlier demonstrated that
muesli enriched with oat β-glucan effectively lowered serum LDL
cholesterol. Addition of plant stanols further lowered LDL cholesterol.
Besides these hypocholesterolemic effects, β-glucan and plant stanol
esters (PSE) may also affect inflammatory processes. Forty-two mildly
hypercholesterolemic subjects randomly consumed for 4 wk (crossover
design) control muesli (4.8 g control fiber), β-glucan muesli (4.8
g oat β-glucan), or combination muesli (4.8 g oat β-glucan plus
1.4 g stanol as PSE). Changes in cytokine production (IL-6, IL-8,
and TNF-α) of LPS-stimulated peripheral blood mononuclear cells
(PBMC) and whole blood were evaluated, as well as changes in plasma
high-sensitivity (hs)-CRP. Additionally, changes in expression profiles
of 84 genes involved in atherosclerosis metabolism were assessed
in isolated PBMC. IL-6, IL-8, and TNF-α production by PBMC and whole
blood after LPS stimulation did not differ between the treatments.
Also high-sensitivity C-reactive protein (hs-CRP) levels were similar.
β-Glucan consumption did not change gene expression, while only
3 genes (ADFP, CDH5, CSF2) out of the 84 genes from the atherosclerotic
risk panel were differentially expressed (p < 0.05) after consumption
of PSE. Consumption of β-glucan with or without PSE did not influence
inflammatory parameters in mildly hypercholesterolemic subjects.},
issn = {1613-4133},
keywords = {Hs-CRP, Human atherosclerosis PCR array, Oat β-glucan, Plant stanol
esters, Proinflammatory cytokines},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/mnfr.200800132}
}
@ARTICLE{Thevenard2011,
author = {Benoît Thevenard and Niriaina Rasoava and Pascal Fourcassié and
Véronique Monnet and Patrick Boyaval and Françoise Rul},
title = {Characterization of Streptococcus thermophilus two-component systems:
In silico analysis, functional analysis and expression of response
regulator genes in pure or mixed culture with its yogurt partner,
Lactobacillus delbrueckii subsp. bulgaricus},
journal = {International Journal of Food Microbiology},
year = {2011},
volume = {151},
pages = {171 - 181},
number = {2},
abstract = {The lactic acid bacterium Streptococcus thermophilus (S. thermophilus)
is widely used in the dairy industry. As a food bacterium, it has
to cope with changing environments such as milk, yogurt, as well
as the digestive tract, after the product has been ingested. In bacteria,
two-component systems (TCS) are one of the most prevalent mechanisms
to sense and respond appropriately to a wide range of signals. They
are typically composed of a sensor kinase (HK) that detects a stimulus
and a response regulator (RR) which acts as a transcriptional regulator.
Our objective was to make an inventory of the TCS present in S. thermophilus
LMD-9 and investigate the contribution of each TCS to LMD-9 growth
in milk. For that purpose, we performed in silico, transcriptomic
as well as functional analysis.
The LMD-9 genome presented 6 complete TCS with both HK and RR (TCS
2, 4, 5, 6, 7, and 9) and 2 orphan RRs (RR01 and 08) with truncated
HK. Our in silico analysis revealed that for 5 TCS out of the 8,
orthologs with known functions were found in other bacterial species
whereas for TCS02, 4 and 6 the function of the orthologs are unidentified.
Transcriptomic studies (using quantitative PCR) revealed that all
S. thermophilus LMD-9 response regulator genes were expressed in
milk; they were expressed at different levels and with different
profiles during growth. In mixed culture with Lactobacillus delbrueckii
subsp. bulgaricus (L. bulgaricus), the S. thermophilus partner in
yogurt, the expression of four S. thermophilus LMD-9 response regulator
increased; two of them, rr02 and rr09, increased by a factor of 6.
These results indicate that the presence of L. bulgaricus induces
regulatory changes in S. thermophilus. We also demonstrated that
a response regulator (rr02) can exert its regulatory function on
its target genes even when expressed at very low levels. We showed
that RR05—an ortholog of Bacillus subtilis YycF or Staphylococcus
aureus WalR—was essential for the growth of S. thermophilus. For
the 7 other RRs, the absence of a single response regulator gene
was insufficient to notably impact the growth of LMD-9 in milk, with
or without supplementation with purines, formate, or stress agents
(lactate, H2O2).
We demonstrated here that the 8 response regulators of LMD-9 are expressed—and
thus potentially active—during growth in milk and suggested that
the response regulators have possibly overlapping regulons and/or
functions not essential under the conditions tested.},
doi = {10.1016/j.ijfoodmicro.2011.08.019},
issn = {0168-1605},
keywords = {Mixed culture},
url = {http://www.sciencedirect.com/science/article/pii/S0168160511004922}
}
@ARTICLE{Thieblemont2011,
author = {Thieblemont, Catherine and Briere, Josette and Mounier, Nicolas and
Voelker, Hans-Ullrich and Cuccuini, Wendy and Hirchaud, Edouard and
Rosenwald, Andreas and Jack, Andrew and Sundstrom, Christer and Cogliatti,
Sergio and Trougouboff, Philippe and Boudova, Ludmila and Ysebaert,
Loic and Soulier, Jean and Chevalier, Catherine and Bron, Dominique
and Schmitz, Norbert and Gaulard, Philippe and Houlgatte, Remi and
Gisselbrecht, Christian},
title = {The Germinal Center/Activated B-Cell Subclassification Has a Prognostic
Impact for Response to Salvage Therapy in Relapsed/Refractory Diffuse
Large B-Cell Lymphoma: A Bio-CORAL Study},
journal = {J. Clin. Oncol.},
year = {2011},
volume = {29},
pages = {4079-4087},
number = {31},
abstract = {PurposeTo evaluate the prognostic value of the cell of origin (COO)
in patients with relapsed/refractory diffuse large B-cell lymphoma
(DLBLC), prospectively treated by rituximab, dexamethasone, high-dose
cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide,
carboplatin, and etoposide and followed by intensive therapy plus
autologous stem-cell transplantation on the Collaborative Trial in
Relapsed Aggressive Lymphoma (CORAL) trial. Patients and MethodsAmong
the 396 patients included on the trial, histologic material was available
for a total of 249 patients at diagnosis (n = 189 patients) and/or
at relapse (n = 147 patients), which included 87 matched pairs. The
patient data were analyzed by immunochemistry for CD10, BCL6, MUM1,
FOXP1, and BCL2 expression and by fluorescent in situ hybridization
for BCL2, BCL6 and c-MYC breakpoints. The correlation with survival
data was performed by using the log-rank test and the Cox model.
ResultsCharacteristics of immunophenotype and chromosomal abnormalities
were statistically highly concordant in the matched biopsies. In
univariate analysis, the presence of c-MYC gene rearrangement was
the only parameter to be significantly correlated with a worse progression-free
survival (PFS; P = .02) and a worse overall survival (P = .04). When
treatment interaction was tested, the germinal center B (GCB) -like
DLBCL that was based on the algorithm by Hans was significantly associated
with a better PFS in the R-DHAP arm. In multivariate analysis, independent
prognostic relevance was found for the GCB/non-GCB the Hans phenotype
interaction treatment (P = .04), prior rituximab exposure (P = .0052),
secondary age-adjusted International Prognostic Index (P = .039),
and FoxP1 expression (P = .047). Confirmation was obtained by gene
expression profiling in a subset of 39 patients. ConclusionCOO remains
a major and independent factor in relapsed/refractory DLBCL, with
a better response to R-DHAP in GCB-like DLBCL. This needs confirmation
by a prospective study.},
doi = {10.1200/JCO.2011.35.4423},
eprint = {http://jco.ascopubs.org/cgi/reprint/29/31/4079.pdf},
url = {http://jco.ascopubs.org/cgi/content/abstract/29/31/4079}
}
@ARTICLE{Thieblemont2004,
author = {Thieblemont, Catherine and Nasser, Valery and Felman, Pascale and
Leroy, Karen and Gazzo, Sophie and Callet-Bauchu, Evelyne and Loriod,
Beatrice and Granjeaud, Samuel and Gaulard, Philippe and Haioun,
Corinne and Traverse-Glehen, Alexandra and Baseggio, Lucile and Bertucci,
Francois and Birnbaum, Daniel and Magrangeas, Florence and Minvielle,
Stephane and Avet-Loiseau, Herve and Salles, Gilles and Coiffier,
Bertrand and Berger, Francoise and Houlgatte, Remi},
title = {Small lymphocytic lymphoma, marginal zone B-cell lymphoma, and mantle
cell lymphoma exhibit distinct gene-expression profiles allowing
molecular diagnosis},
journal = {Blood},
year = {2004},
volume = {103},
pages = {2727--2737},
number = {7},
month = apr,
abstract = {Non-germinal center small B-cell lymphomas represent a heterogeneous
group of non-Hodgkin lymphomas, the most frequent histologic subtypes
being small lymphocytic lymphoma (SLL), splenic marginal zone B-cell
lymphoma (MZL), and mantle cell lymphoma (MCL). In order to identify
genomic signatures specific for each disease, we analyzed 128 primary
tumors using high-density microarrays. Several clusters of genes
significantly discriminated the 3 histologic subtypes. Genes associated
with cell adhesion, angiogenesis, and inhibition of apoptosis were
up-regulated in SLL. Genes associated with intracellular signaling
via the AKT1 pathway were up-regulated in splenic MZL. Genes associated
with cell cycle control and multidrug resistance were up-regulated
in MCL. Using 44 genes selected within the gene clusters discriminant
for the 3 lymphoma subtypes, we generated a class prediction score
that allowed us to classify the 3 entities in 96% of the cases, including
borderline cases. Whereas specific transcriptional profiles easily
distinguished all MZL samples, SLL samples, and most of the MCL samples
into separate groups, few MCL cases exhibited MZL-type transcriptional
profiles. This study demonstrates that SLL, splenic MZL, and MCL
possess specific transcriptional profiles that may be relevant to
the pathogenesis and the diagnosis of these histologic subtypes.
(Blood. 2004;103:2727-2737)},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/103/7/2727}
}
@ARTICLE{Thiel2011,
author = {Thiel, Johannes and Rolletschek, Hardy and Friedel, Svetlana and
Lunn, John and Nguyen, Thuy and Feil, Regina and Tschiersch, Henning
and Muller, Martin and Borisjuk, Ljudmilla},
title = {Seed-specific elevation of non-symbiotic hemoglobin AtHb1: beneficial
effects and underlying molecular networks in Arabidopsis thaliana},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {48},
number = {1},
abstract = {BACKGROUND:Seed metabolism is dynamically adjusted to oxygen availability.
Processes underlying this auto-regulatory mechanism control the metabolic
efficiency under changing environmental conditions/stress and thus,
are of relevance for biotechnology. Non-symbiotic hemoglobins have
been shown to be involved in scavenging of nitric oxide (NO) molecules,
which play a key role in oxygen sensing/balancing in plants and animals.
Steady state levels of NO are suggested to act as an integrator of
energy and carbon metabolism and subsequently, influence energy-demanding
growth processes in plants.RESULTS:We aimed to manipulate oxygen
stress perception in Arabidopsis seeds by overexpression of the non-symbiotic
hemoglobin AtHb1 under the control of the seed-specific LeB4 promoter.
Seeds of transgenic AtHb1 plants did not accumulate NO under transient
hypoxic stress treatment, showed higher respiratory activity and
energy status compared to the wild type. Global transcript profiling
of seeds/siliques from wild type and transgenic plants under transient
hypoxic and standard conditions using Affymetrix ATH1 chips revealed
a rearrangement of transcriptional networks by AtHb1 overexpression
under non-stress conditions, which included the induction of transcripts
related to ABA synthesis and signaling, receptor-like kinase- and
MAP kinase-mediated signaling pathways, WRKY transcription factors
and ROS metabolism. Overexpression of AtHb1 shifted seed metabolism
to an energy-saving mode with the most prominent alterations occurring
in cell wall metabolism. In combination with metabolite and physiological
measurements, these data demonstrate that AtHb1 overexpression improves
oxidative stress tolerance compared to the wild type where a strong
transcriptional and metabolic reconfiguration was observed in the
hypoxic response.CONCLUSIONS:AtHb1 overexpression mediates a pre-adaptation
to hypoxic stress. Under transient stress conditions transgenic seeds
were able to keep low levels of endogenous NO and to maintain a high
energy status, in contrast to wild type. Higher weight of mature
transgenic seeds demonstrated the beneficial effects of seed-specific
overexpression of AtHb1.},
doi = {10.1186/1471-2229-11-48},
issn = {1471-2229},
pubmedid = {21406103},
url = {http://www.biomedcentral.com/1471-2229/11/48}
}
@ARTICLE{Thierry2011,
author = {Thierry, Dulermo and Jean-Marc, Nicaud},
title = {Involvement of the G3P shuttle and [beta]-oxidation pathway in the
control of TAG synthesis and lipid accumulation in Yarrowia lipolytica},
journal = {Metabolic Engineering},
year = {2011},
volume = {13, 5},
pages = {482–491},
abstract = {The oleaginous yeast Yarrowia lipolytica can accumulate up to 38%
of its dry weight (DW) as lipids. Factors involved in lipid accumulation,
particularly triglycerides, are not well identified. Using different
mutations in the glycerol-3-phosphate (G3P) shuttle pathway ([Delta]gut2
affecting the anabolic dehydrogenase or overexpressing GPD1 affecting
the catabolic dehydrogenase), we were able to modulate G3P concentration.
We show that in a Po1d genetic background, GPD1 overexpression, GUT2
inactivation or both mutations together result in 1.5, 2.9 and 5.6-fold
respective increases in the level of G3P leading to an increase of
triacylglyceride (TAG) accumulation. Moreover, our results indicate
that each strain with an increased concentration of G3P, also presented
a decreased concentration of glycerol. Analysis of the different
genes involved in glycerol metabolism indicated that Y. lipolytica
does not possess a gene for glycerol-3-phosphatase. These findings
suggest that Y. lipolytica has a modified and unique metabolism of
glycerol that is dedicated to G3P synthesis (and also to TAG synthesis)
which may contribute to its oleaginous character. Furthermore, coupling
the G3P shuttle disorders to a deficient [beta]-oxidation pathway
(by inactiving POX1-6 or MFE1 genes) increased TAG and free fatty
acids content. Finally we obtained strains that accumulated up to
65-75% of their DW as lipid. Transcriptional analysis in these strains,
revealed that the high levels of lipids resulted from over-expression
of genes involved in TAG synthesis (SCT1, encoding a sn-1 acyltransferase;
and DGA1, encoding an acylCoA diacylglycerol acyltransferase) and
the repression of genes involved in the degradation of TAG (TGL3
and TGL4, encoding triacylglycerol lipases). These findings indicate
that TAG synthesis is limited by the availability of G3P and fatty
acids, and that the expression of genes involved in TAG homeostasis
is regulated by the G3P shuttle and the [beta]-oxidation pathway.
Finally, the synergistic contribution of acyltransferase gene expression
to G3P synthesis is required for high levels of TAG synthesis and
lipid accumulation in Y. lipolytica.},
issn = {1096-7176},
keywords = {Triacylglyceride, Glycerol metabolism, Lipids, Yarrowia lipolytica,
Glycerol-3-phosphate, Glycerol-3-phosphate shuttle},
url = {http://www.sciencedirect.com/science/article/pii/S1096717611000516}
}
@ARTICLE{Thierry2004,
author = {Thierry, Francoise and Benotmane, Mohammed Abderrafi and Demeret,
Caroline and Mori, Marcella and Teissier, Sebastien and Desaintes,
Christian},
title = {A Genomic Approach Reveals a Novel Mitotic Pathway in Papillomavirus
Carcinogenesis},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {895--903},
number = {3},
month = feb,
abstract = {More than 90% of cervical carcinomas are associated with human papillomavirus
(HPV) infection. The two viral oncogenes E6 and E7 play a major role
in transforming the cells by disrupting p53- and pRb-dependent cell
cycle checkpoints. A hallmark of HPV-associated cervical carcinoma
is loss of the expression of the viral E2 protein, often by disruption
of E2-encoding gene. We showed previously that reintroduction of
E2 in HPV18-associated cervical carcinoma cells induces cell cycle
arrest in G1 because of the transcriptional repression of the viral
oncogenes E6 and E7 and concomitant reactivation of the p53 and pRb
pathways. Here we describe global gene profiling of HeLa cells expressing
different HPV18 E2 mutants to study the effects of repression of
the viral oncogenes. We identified 128 genes transcriptionally regulated
by the viral oncogenes in cervical carcinoma. Surprisingly, E2 repressed
a subset of E2F-regulated mitotic genes in an E6/E7-dependent pathway.
This was corroborated by the observation that E2 delayed mitotic
progression, suggesting the involvement of a mitotic pathway in HPV
carcinogenesis. These mitotic genes constitute an as yet unrecognized
set of genes, which were also found deregulated in other HPV-associated
cervical carcinoma cell lines and therefore represent new targets
for both diagnosis and therapeutic approaches in cervical cancer.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/3/895}
}
@ARTICLE{Thimm2004,
author = {Thimm, Oliver and Bläsing, Oliver and Gibon, Yves and Nagel, Axel
and Meyer, Svenja and Krüger, Peter and Selbig, Joachim and Müller,
Lukas A. and Rhee, Seung Y. and Stitt, Mark},
title = {mapman: a user-driven tool to display genomics data sets onto diagrams
of metabolic pathways and other biological processes},
journal = {The Plant Journal},
year = {2004},
volume = {37},
pages = {914--939},
number = {6},
abstract = {Summary mapman is a user-driven tool that displays large data sets
onto diagrams of metabolic pathways or other processes. SCAVENGER
modules assign the measured parameters to hierarchical categories
(formed ‘BINs’, ‘subBINs’). A first build of transcriptscavenger
groups genes on the Arabidopsis Affymetrix 22K array into >200 hierarchical
categories, providing a breakdown of central metabolism (for several
pathways, down to the single enzyme level), and an overview of secondary
metabolism and cellular processes. metabolitescavenger groups hundreds
of metabolites into pathways or groups of structurally related compounds.
An imageannotator module uses these groupings to organise and display
experimental data sets onto diagrams of the users' choice. A modular
structure allows users to edit existing categories, add new categories
and develop SCAVENGER modules for other sorts of data. mapman is
used to analyse two sets of 22K Affymetrix arrays that investigate
the response of Arabidopsis rosettes to low sugar: one investigates
the response to a 6-h extension of the night, and the other compares
wild-type Columbia-0 (Col-0) and the starchless pgm mutant (plastid
phosphoglucomutase) at the end of the night. There were qualitatively
similar responses in both treatments. Many genes involved in photosynthesis,
nutrient acquisition, amino acid, nucleotide, lipid and cell wall
synthesis, cell wall modification, and RNA and protein synthesis
were repressed. Many genes assigned to amino acid, nucleotide, lipid
and cell wall breakdown were induced. Changed expression of genes
for trehalose metabolism point to a role for trehalose-6-phosphate
(Tre6P) as a starvation signal. Widespread changes in the expression
of genes encoding receptor kinases, transcription factors, components
of signalling pathways, proteins involved in post-translational modification
and turnover, and proteins involved in the synthesis and sensing
of cytokinins, abscisic acid (ABA) and ethylene revealing large-scale
rewiring of the regulatory network is an early response to sugar
depletion.},
issn = {1365-313X},
keywords = {data display, expression profiling, metabolite profiling, sugar sensing},
publisher = {Blackwell Science, Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2004.02016.x}
}
@ARTICLE{Thimm2001,
author = {Thimm, Oliver and Essigmann, Bernd and Kloska, Sebastian and Altmann,
Thomas and Buckhout, Thomas J.},
title = {Response of Arabidopsis to Iron Deficiency Stress as Revealed by
Microarray Analysis},
journal = {Plant Physiology},
year = {2001},
volume = {127},
pages = {1030--1043},
number = {3},
month = nov,
abstract = {Gene expression in response to Fe deficiency was analyzed in Arabidopsis
roots and shoots through the use of a cDNA collection representing
at least 6,000 individual gene sequences. Arabidopsis seedlings were
grown 1, 3, and 7 d in the absence of Fe, and gene expression in
roots and shoots was investigated. Following confirmation of data
and normalization methods, expression of several sequences encoding
enzymes known to be affected by Fe deficiency was investigated by
microarray analysis. Confirmation of literature reports, particularly
for changes in enzyme activity, was not always possible, but changes
in gene expression could be confirmed. An expression analysis of
genes in glycolysis, the tricarboxylic acid cycle, and oxidative
pentose phosphate pathway revealed an induction of several enzymes
within 3 d of Fe-deficient growth, indicating an increase in respiration
in response to Fe deficiency. In roots, transcription of sequences
corresponding to enzymes of anaerobic respiration was also induced,
whereas in shoots, the induction of several genes in gluconeogenesis,
starch degradation, and phloem loading was observed. Thus, it seemed
likely that the energy demand in roots required for the Fe deficiency
response exceeded the capacity of oxidative phosphorylation, and
an increase in carbon import and anaerobic respiration were required
to maintain metabolism.},
url = {http://www.plantphysiol.org/cgi/content/abstract/127/3/1030}
}
@ARTICLE{Thimon2008,
author = {Thimon, Veronique and Calvo, Ezequiel and Koukoui, Omedine and Legare,
Christine and Sullivan, Robert},
title = {Effects of Vasectomy on Gene Expression Profiling along the Human
Epididymis},
journal = {Biol Reprod},
year = {2008},
volume = {79},
pages = {262--273},
number = {2},
month = aug,
abstract = {Worldwide, almost 100 million men rely on vasectomy for male contraceptive
purposes. Due to changes in their personal lives, an increasing number
of these men request surgical vasectomy reversal. Unfortunately,
a significant proportion of these men remain infertile, despite the
reestablishment of patent ducts, possibly due to epididymal damage
caused by vasectomy. In animal models, vasectomy affects different
epididymal physiological and biochemical parameters. However, the
consequences of vasectomy on epididymal function are poorly understood.
Furthermore, results obtained with animal models cannot be extrapolated
to humans to understand the consequences of vasectomy on epididymal
function. Gene expression along the epididymis is highly regulated.
We previously showed that the human epididymal expression pattern
of two genes is altered after vasectomy. To complete the list of
epididymal genes affected by vasectomy, we analyzed the epididymal
gene expression pattern of three vasectomized donors using the Affymetrix
human GeneChip U133 Plus 2. These results were compared with the
gene expression pattern of three "normal" donors. The data generated
allowed the identification of many human epididymal genes for which
expression is modified after vasectomy. Quantitative (Qt)-PCR and
Western blot analysis of six selected genes known to be expressed
in specific epididymal segments were performed. The Qt-PCR results
confirmed the selected transcripts expression pattern deduced from
microarray data. However, Western blot analysis revealed some differences
in protein distribution along the epididymis when compared with the
encoding transcripts expression pattern. These results contribute
to an understanding of the reasons why fertility is not recovered
in vasovasostomized men, even though spermogram values suggest surgical
success of vasectomy reversal.},
url = {http://www.biolreprod.org/cgi/content/abstract/79/2/262}
}
@ARTICLE{Thimon2007,
author = {Thimon, Veronique and Koukoui, Omedine and Calvo, Ezequiel and Sullivan,
Robert},
title = {Region-specific gene expression profiling along the human epididymis},
journal = {Mol. Hum. Reprod.},
year = {2007},
volume = {13},
pages = {691--704},
number = {10},
month = oct,
abstract = {During their transit through the epididymis, spermatozoa undergo many
biochemical modifications necessary to acquire flagellar motility
and fertilizing ability. These modifications, collectively called
sperm maturation, are well orchestrated along the epididymis and
depend on highly regionalized gene expression patterns. Based on
clinical observations, the role of the epididymis in human sperm
maturation has been questioned. To further understand the function
of the excurrent duct in humans, we analysed gene expression of three
donors on Affymetrix human GeneChip U133 plus 2' representing 47
000 transcriptional variants. More than 50% of transcripts were detected
in each epididymal region. The analysis of hierarchical clustering
performed from 2274 modulated qualifers between the three regions
revealed that 1184, 713 and 269 were highly expressed in the caput,
corpus and cauda region, respectively, in a very specific manner.
The expressed qualifers were grouped according their similarity by
Gene Ontology to give an overview of the functional features of the
encoded proteins and to elucidate their potential roles in the epididymis.
Northern blot analysis of eight gene transcripts predicted by microarray
data to be highly expressed in the human epididymis was performed.
All the transcript expression patterns confirmed the microarrays
results. The data generated in this study demonstrate a region-specific
gene expression pattern along the human epididymis that seems to
coincide with the morphologically distinctive features of the excurrent
duct.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/13/10/691}
}
@ARTICLE{Thirlwell2010,
author = {Thirlwell, Christina and Eymard, Marianne and Feber, Andrew and Teschendorff,
Andrew and Pearce, Kerra and Lechner, Matthias and Widschwendter,
Martin and Beck, Stephan},
title = {Genome-wide DNA methylation analysis of archival formalin-fixed paraffin-embedded
tissue using the Illumina Infinium HumanMethylation27 BeadChip},
journal = {Methods},
year = {2010},
volume = {52},
pages = {248--254},
number = {3},
month = nov,
abstract = {Aberrant DNA methylation of promoter and other genomic regions can
lead to changes in gene expression, such as over-expression of oncogenes
and the silencing of tumour suppressor genes in the context of cancer.
Ability to accurately assess the DNA methylation status is therefore
of great importance in health and disease. Recently, various platforms
for genome-wide analysis of promoter DNA methylation have been developed,
including the Illumina Infinium platform. While some of these platforms
can be used with formalin-fixed paraffin-embedded (FFPE) tissue,
no protocol has yet been developed for the analysis of FFPE-derived
DNA on the Infinium platform using the HumanMethylation27 BeadChip
which interrogates 27,578 cytosine-guanine (CpG) dinucleotide sites,
selected predominantly from the promoter regions of 14,000 annotated
genes. As FFPE preservation has been the method of choice for the
archiving of clinical samples, the ability to analyse such samples
opens the possibility to study large numbers of clinically well annotated
samples which can be expected to lead to more powerful and robust
data, particularly for rare cancers. Here, we describe a protocol
for the analysis of FFPE samples using the Infinium HumanMethylation27
BeadChip.},
booktitle = {DNA Methylation Analysis},
issn = {1046-2023},
keywords = {CpG dinucleotide, Genome-wide analysis, DNA methylation, Differentially
methylated region (DMR), Formalin-fixed paraffin-embedded (FFPE)
tissue, Methylome},
url = {http://www.sciencedirect.com/science/article/B6WN5-4YYRMR8-1/2/70e57d042aa1fd103a7bf387dfbf68af}
}
@ARTICLE{Thirunavukkarasu2008,
author = {Thirunavukkarasu, M. and Addya, S. and Juhasz, B. and Pant, R. and
Zhan, L. and Surrey, S. and Maulik, G. and Menon, V. P. and Maulik,
N.},
title = {Heterozygous disruption of Flk-1 receptor leads to myocardial ischaemia
reperfusion injury in mice: application of affymetrix gene chip analysis},
journal = {Journal of Cellular and Molecular Medicine},
year = {2008},
volume = {12},
pages = {1284--1302},
number = {4},
abstract = {Abstract This study addresses an important clinical issue by identifying
potential candidates of vascular endothelial growth factor (VEGF)
signalling through the Flk-1 receptor that trigger cardioprotective
signals under ischaemic stress. Isolated working mouse hearts of
both wild-type (WT) and Flk-1+/− were subjected to global ischaemia
(I) for 30 min. followed by 2 hrs of reperfusion (R). Flk-1+/−
myocardium displayed almost 50% reduction in Flk-1 mRNA as examined
by quantitative real-time RT-PCR at the baseline level. Flk-1+/−
mouse hearts displayed reduction in left ventricular functional recovery
throughout reperfusion (dp/dt 605 versus 884), after 2 hrs (P < 0.05).
Coronary (1.9 versus 2.4 ml) and aortic flow (AF) (0.16 versus 1.2
ml) were reduced in Flk-1+/− after 2 hrs of reperfusion. In addition,
increased infarct size (38.4%versus 28.41%, P < 0.05) and apoptotic
cardiomyocytes (495 versus 213) were observed in Flk-1+/− knockout
(KO) mice. We also examined whether ischaemic preconditioning (PC),
a novel method to induce cardioprotection against ischaemia reperfusion
injury, through stimulating the VEGF signalling pathway might function
in Flk-1+/− mice. We found that knocking down Flk-1 resulted in
significant reduction in the cardioprotective effect by PC compared
to WT. Affymetrix gene chip analysis demonstrated down-regulation
of important genes after IR and preconditioning followed by ischaemia
reperfusion in Flk-1+/− mice compared to WT. To get insight into
the underlying molecular pathways involved in ischaemic PC, we determined
the distinct and overlapping biological processes using Ingenuity
pathway analysis tool. Independent evidence at the mRNA level supporting
the Affymetrix results were validated using real-time RT-PCR for
selected down-regulated genes, which are thought to play important
roles in cardioprotection after ischaemic insult. In summary, our
data indicated for the first time that ischaemic PC modifies genomic
responses in heterozygous VEGFR-2/Flk-1 KO mice and abolishes its
cardioprotective effect on ischaemic myocardium.},
issn = {1582-4934},
keywords = {ischaemia, reperfusion, Flk-1, myocardium, affymetrix gene chip, gene
expression},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2008.00269.x}
}
@ARTICLE{Thomas2007,
author = {Thomas, B. and Eyries, M. and Montagne, K. and Martin, S. and Agrapart,
M. and Simerman-François, R. and Letarte, M. and Soubrier, F.},
title = {Altered endothelial gene expression associated with hereditary haemorrhagic
telangiectasia},
journal = {European Journal of Clinical Investigation},
year = {2007},
volume = {37},
pages = {580--588},
number = {7},
abstract = {Abstract Background  Mutations in endoglin (ENG) and activin receptor-like
kinase 1 (ALK-1 or ACVRL1) genes are the underlying basis of hereditary
haemorrhagic telangiectasia (HHT) types 1 and 2, respectively. Both
genes belong to the transforming growth factor-β (TGF-β) receptors
superfamily and are expressed in endothelial cells. The current model
for HHT is that ENG or ALK-1 haplo-insufficiency affects angiogenesis
and predisposes to vascular dysplasia and arteriovenous malformations.
Materials and methods  Using microarray technology, we compared
human umbilical vein endothelial cells (HUVEC) from newborns with
ENG or ALK-1 mutations to control cells to search for gene profiles
associated with early stages of the disease. Real-time polymerase
chain reaction and Western blot analysis were used to validate a
subset of the modulated genes and functionally related genes. Results 
Our results indicate that HHT endothelial cells in vitro display
several gene expression disturbances, including genes associated
with the activation phase of angiogenesis, with cell guidance and
intercellular connections, and also with the TGF-β pathway. Hierarchical
clustering using modulated genes enables discrimination between affected
and non-affected samples. Conclusion  HHT HUVECs display gene modulations
which can suggest that ENG and ALK-1 haplo-insufficiency induces
compensatory regulatory mechanisms at the expression levels.},
issn = {1365-2362},
keywords = {expression profiling, Rendu-Osler-Weber disease, vascular hereditary
disease.},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2362.2007.01824.x}
}
@ARTICLE{Thomas2008,
author = {Thomas, Catherine A. and Grant, Stephen G. and Pflug, Beth R. and
Getzenberg, Robert H. and Day, Billy W.},
title = {(Z)-1,1-Dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane induces
concentration-dependent growth inhibition, apoptosis, and coordinates
regulation of apoptotic genes in TRAMP cells},
journal = {Urologic Oncology: Seminars and Original Investigations},
year = {2008},
volume = {26},
pages = {378--385},
number = {4},
month = jul,
abstract = {(Z)-1-1-Dichloro-2,3-diphenylcyclopropane (AII) and (Z)-1,1-dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane
[2-(4-methoxyphenyl)-AII] inhibit tubulin polymerization, PSA production,
and the proliferation of human prostate cancer cells. The actions
of the agents were studied in three transgenic adenocarcinomas of
the mouse prostate (TRAMP) cell lines. Antiproliferative potencies
were determined and cells treated with the more potent 2-(4-methoxyphenyl)-AII
were examined for induction of apoptosis. Microarray analyses were
conducted to determine the apoptosis-related genes up- and down-regulated
by the agent. 2-(4-Methoxyphenyl)-AII concentration-dependently inhibited
growth of all three cell lines. Fifty percent and 100% growth inhibitory
and 50% lethal concentrations were determined to be 0.3, 1.5, and
5 [mu]M, respectively. Minimum detectable apoptosis-inducing concentrations
by ELISA were 0.10 to 0.14 [mu]M. PARP cleavage and two-color flow
cytometry assays verified apoptosis induction. Microarray analyses
showed Bok and Siva-pending to be up-regulated and that Birc, Dad1,
and Atf5 were down-regulated. 2-(4-methoxyphenyl)-AII inhibits proliferation
and induces apoptosis in the in vivo-adaptable TRAMP cells, suggesting
the compound should be further examined in preclinical models.},
booktitle = {Evolving New Treatments For Patients With Prostate Cancer: The Advanced
Disease Paradigm of the PSA Era},
issn = {1078-1439},
keywords = {Prostate cancer, Microtubule inhibitor, Microarray, TRAMP cells, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6TD3-4RD9FMG-1/2/09a0264decbe792e8e196c358e72cdb8}
}
@ARTICLE{Thomas2004,
author = {Thomas, David M. and Francescutti-Verbeem, Dina M. and Liu, Xiuli
and Kuhn, Donald M.},
title = {Identification of differentially regulated transcripts in mouse striatum
following methamphetamine treatment – an oligonucleotide microarray
approach},
journal = {Journal of Neurochemistry},
year = {2004},
volume = {88},
pages = {380--393},
number = {2},
abstract = {Abstract Methamphetamine is an addictive drug of abuse that can produce
neurotoxic effects in dopamine nerve endings of the striatum. The
purpose of this study was to identify new genes that may play a role
in the highly complex cascade of events associated with methamphetamine
intoxication. Using Affymetrix oligonucleotide arrays, 12Â 488 genes
were simultaneously interrogated and there were 152 whose expression
levels were changed following methamphetamine treatment. The genes
are grouped into broad functional categories with inflammatory/immune
response elements, receptor/signal transduction components and ion
channel/transport proteins among the most populated. Many genes within
these categories can be linked to ion regulation and apoptosis, both
of which have been implicated in methamphetamine toxicity, and numerous
factors associated with microglial activation emerged with significant
changes in expression. For example, brain-derived neurotrophic factor
(BDNF), chemokine (C-C) receptor 6 (CCr6) and numerous chemokine
transcripts were increased or decreased in expression more than 2.8-fold.
These results point to activated microglia as a potential source
of the reactive oxygen/nitrogen species and cytokines that have been
previously associated with methamphetamine toxicity and other neurotoxic
conditions.},
issn = {1471-4159},
keywords = {chemokines, cytokines, inflammation, methamphetamine, microarray,
striatum},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1046/j.1471-4159.2003.02182.x}
}
@ARTICLE{Thomas2008a,
author = {Thomas, Elizabeth A. and Coppola, Giovanni and Desplats, Paula A.
and Tang, Bin and Soragni, Elisabetta and Burnett, Ryan and Gao,
Fuying and Fitzgerald, Kelsey M. and Borok, Jenna F. and Herman,
David and Geschwind, Daniel H. and Gottesfeld, Joel M.},
title = {The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional
abnormalities in Huntington's disease transgenic mice},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {15564--15569},
number = {40},
month = oct,
abstract = {Transcriptional dysregulation has emerged as a core pathologic feature
of Huntington's disease (HD), one of several triplet-repeat disorders
characterized by movement deficits and cognitive dysfunction. Although
the mechanisms contributing to the gene expression deficits remain
unknown, therapeutic strategies have aimed to improve transcriptional
output via modulation of chromatin structure. Recent studies have
demonstrated therapeutic effects of commercially available histone
deacetylase (HDAC) inhibitors in several HD models; however, the
therapeutic value of these compounds is limited by their toxic effects.
Here, beneficial effects of a novel pimelic diphenylamide HDAC inhibitor,
HDACi 4b, in an HD mouse model are reported. Chronic oral administration
of HDACi 4b, beginning after the onset of motor deficits, significantly
improved motor performance, overall appearance, and body weight of
symptomatic R6/2300Q transgenic mice. These effects were associated
with significant attenuation of gross brain-size decline and striatal
atrophy. Microarray studies revealed that HDACi 4b treatment ameliorated,
in part, alterations in gene expression caused by the presence of
mutant huntingtin protein in the striatum, cortex, and cerebellum
of R6/2300Q transgenic mice. For selected genes, HDACi 4b treatment
reversed histone H3 hypoacetylation observed in the presence of mutant
huntingtin, in association with correction of mRNA expression levels.
These findings suggest that HDACi 4b, and possibly related HDAC inhibitors,
may offer clinical benefit for HD patients and provide a novel set
of potential biomarkers for clinical assessment.},
url = {http://www.pnas.org/cgi/content/abstract/105/40/15564}
}
@ARTICLE{Thomas2011,
author = {Thomas, Elizabeth A. and Coppola, Giovanni and Tang, Bin and Kuhn,
Alexandre and Kim, SoongHo and Geschwind, Daniel H. and Brown, Timothy
B. and Luthi-Carter, Ruth and Ehrlich, Michelle E.},
title = {In vivo cell-autonomous transcriptional abnormalities revealed in
mice expressing mutant huntingtin in striatal but not cortical neurons},
journal = {Hum. Mol. Genet.},
year = {2011},
volume = {20},
pages = {1049--1060},
number = {6},
month = mar,
abstract = {Huntington's disease (HD), caused by a CAG repeat expansion in the
huntingtin (HTT) gene, is characterized by abnormal protein aggregates
and motor and cognitive dysfunction. Htt protein is ubiquitously
expressed, but the striatal medium spiny neuron (MSN) is most susceptible
to dysfunction and death. Abnormal gene expression represents a core
pathogenic feature of HD, but the relative roles of cell-autonomous
and non-cell-autonomous effects on transcription remain unclear.
To determine the extent of cell-autonomous dysregulation in the striatum
in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q
(a.k.a. DE5) transgenic mice in which the forebrain expression of
the first 171 amino acids of human Htt with a 98Q repeat expansion
is limited to MSNs. Microarray data generated from these mice were
compared with those generated on the identical array platform from
a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat
lengths, and a relatively high degree of overlap of changes in gene
expression was revealed. We further focused on known canonical pathways
associated with excitotoxicity, oxidative stress, mitochondrial dysfunction,
dopamine signaling and trophic support. While genes related to excitotoxicity,
dopamine signaling and trophic support were altered in both DE5 and
R6/2 mice, which may be either cell autonomous or non-cell autonomous,
genes related to mitochondrial dysfunction, oxidative stress and
the peroxisome proliferator-activated receptor are primarily affected
in DE5 transgenic mice, indicating cell-autonomous mechanisms. Overall,
HD-induced dysregulation of the striatal transcriptome can be largely
attributed to intrinsic effects of mutant Htt, in the absence of
expression in cortical neurons.},
comment = {10.1093/hmg/ddq548},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/20/6/1049}
}
@ARTICLE{Thomas2007a,
author = {Thomas, Geraldine A. and Tuttle, Michael},
title = {The Chernobyl Tissue Bank, an international collaboration to investigate
the relationship between the exposure to radiation in childhood and
thyroid cancer},
journal = {International Congress Series},
year = {2007},
volume = {1299},
pages = {167--173},
month = feb,
abstract = {The only unequivocal radiological effect of the Chernobyl accident
on human health is the increase in thyroid cancer in those exposed
in childhood. In response to the scientific interest in studying
the molecular biology of thyroid cancer post-Chernobyl, the Chernobyl
Tissue Bank (CTB: www.chernobyltissuebank.com) was established. The
project is supported by the governments of Ukraine and Russia, and
financially supported (US$3 M) by the European Commission, the National
Cancer Institute of the USA, the Sasakawa Memorial Health Foundation
of Japan and the World Health Organization. Full informed consent
is obtained from donors; each case is subject to pathological review
by an international panel. Aliquots of extracted nucleic acid (RNA
and DNA from tissue, DNA from blood) serum are made available to
researchers worldwide. Quality control is carried out on each extracted
tissue and blood sample; the presence of tumour is confirmed by frozen
section prior to extraction. 1605 cases have been pathologically
reviewed so far; frozen samples are available on 1254. The majority
of the cases are papillary carcinomas (924). Paired tumour-normal
samples are available; extracted nucleic acid is available on 337
cases. Samples of blood are available from 711 of the 1605 reviewed
cases. Material from the project is currently being used for a variety
of scientific projects in Europe, the US and Japan, using techniques
from cDNA array and comparative genomic hybridization to immunocytochemistry.
More than 2000 aliquots of nucleic acid and 5000 paraffin sections
have been released. Researchers using the resource agree to provide
their results back to the project on a case-by-case basis for entry
into the project database in Swansea.},
booktitle = {Radiation Risk Perspectives: Proceedings of the Second Nagasaki Symposium
of International Consortium for Medical Care of Hibakusha and Radiation
Life Science, Nagasaki, Japan, 26-27 July 2006},
issn = {0531-5131},
keywords = {Chernobyl, Tissue bank, Molecular biology},
url = {http://www.sciencedirect.com/science/article/B7581-4N7YJVJ-12/2/97e3d4ecfe80320bc8f3d47ea5a97909}
}
@ARTICLE{Thomas2012,
author = {Michael A. Thomas and Parag P. Joshi and Rebecca D. Klaper},
title = {Gene-class analysis of expression patterns induced by psychoactive
pharmaceutical exposure in fathead minnow (Pimephales promelas) indicates
induction of neuronal systems},
journal = {Comparative Biochemistry and Physiology Part C: Toxicology \&
Pharmacology},
year = {2012},
volume = {155},
pages = {109 - 120},
number = {1},
note = {Special Issue dedicated to 5th Aquatic Animal Models of
Human Disease meeting: Corvallis, OR, USA, September 20-22, 2010},
abstract = {Psychoactive pharmaceuticals are among the most frequently prescribed
drugs, contributing to persistent measurable concentrations in aquatic
systems. Typically, it is assumed that such contaminants have no
human health implications because they exist in extremely low concentrations.
We exposed juvenile fathead minnows (Pimephales promelas) to three
pharmaceuticals, fluoxetine, venlafaxine and carbamazepine, individually
and in a mixture, and measured their effect on the induction of gene
expression in fish brains using microarray analysis. Gene expression
changes were accompanied by behavioral changes and validated by qPCR
analysis. Gene Set Enrichment Analysis was used to perform gene-class
analysis of gene expression, testing for enrichment of gene sets
known to be involved in human neuronal development, regulation and
growth. We found significant enrichment of gene sets for each of
the treatments, with the largest induction of expression by the mixture
treatment. These results suggest that the psychoactive pharmaceuticals
are able to alter expression of fish genes associated with development,
regulation and differentiation of synapses, neurons and neurotransmitters.
The results provide a new perspective for the consideration of potential
consequence for human health due to environmental exposure to unmetabolized
psychoactive pharmaceuticals.},
doi = {10.1016/j.cbpc.2011.05.014},
issn = {1532-0456},
keywords = {GSEA},
url = {http://www.sciencedirect.com/science/article/pii/S1532045611001037}
}
@ARTICLE{Thomas2006,
author = {Thomas, Matthew J. and Agy, Michael B. and Proll, Sean C. and Paeper,
Bryan W. and Li, Yu and Jensen, Kara L. and Korth, Marcus J. and
Katze, Michael G.},
title = {Functional gene analysis of individual response to challenge of SIVmac239
in M. mulatta PBMC culture},
journal = {Virology},
year = {2006},
volume = {348},
pages = {242--252},
number = {1},
month = apr,
abstract = {It has previously been shown in macaques that individual animals exhibit
varying responses to challenge with the same strain of SIV. We attempted
to elucidate these differences using functional genomics and correlate
them to biological response. Unfractionated PBMC from three rhesus
macaques were isolated, activated, and infected with SIVmac239. Interestingly,
one of the three animals used for these experiments exhibited a completely
unique response to infection relative to the other two. After repeated
attempts to infect the PBMC from this animal, little or no infectivity
was seen across the time points considered, and corresponding to
this apparent lack of infection, few genes were seen to be differentially
expressed when compared to mock-infected cells. For the remaining
two animals, gene expression analysis showed that while they exhibited
responses for the same groups of pathways, these responses included
differences specific to the individual animal at the gene level.
In instances where the patterns of differential gene expression differed
between these animals, the genes being differentially expressed were
associated with the same categories of biological process, mainly
immune response and cell signaling. At the pathway level, these animals
again exhibited similar responses that could be predicted based on
the experimental conditions. Even in these expected results, the
degree of response and the specific genes being regulated differed
greatly from animal to animal. The differences in gene expression
on an individual level have the potential to be used as markers in
identification of animals suitable for lentiviral infection experiments.
Our results highlight the importance of individual variation in response
to viral challenge.},
issn = {0042-6822},
keywords = {Gene expression, Microarray, Peripheral blood mononuclear cells, Simian
immunodeficiency virus},
url = {http://www.sciencedirect.com/science/article/B6WXR-4J3NY28-2/2/ce292b8d091820145be9d4aeb4139abc}
}
@ARTICLE{Thomas2009,
author = {Thomas, Reuben and Gohlke, Julia and Stopper, Geffrey and Parham,
Frederick and Portier, Christopher},
title = {Choosing the right path: enhancement of biologically relevant sets
of genes or proteins using pathway structure},
journal = {Genome Biology},
year = {2009},
volume = {10},
pages = {R44},
number = {4},
abstract = {A method is proposed that finds enriched pathways relevant to a studied
condition using the measured molecular data and also the structural
information of the pathway viewed as a network of nodes and edges.
Tests are performed using simulated data and genomic data sets and
the method is compared to two existing approaches. The analysis provided
demonstrates the method proposed is very competitive with the current
approaches and also provides biologically relevant results.},
doi = {10.1186/gb-2009-10-4-r44},
issn = {1465-6906},
pubmedid = {19393085},
url = {http://genomebiology.com/2009/10/4/R44}
}
@ARTICLE{Thomas2006a,
author = {Thomas, Ronald D. and Green, Mario R. and Wilson, Chantell and Weckle,
Amy L. and Duanmu, Zhengbo and Kocarek, Thomas A. and Runge-Morris,
Melissa},
title = {Cytochrome P450 expression and metabolic activation of cooked food
mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in
MCF10A breast epithelial cells},
journal = {Chemico-Biological Interactions},
year = {2006},
volume = {160},
pages = {204--216},
number = {3},
month = apr,
abstract = {The cytochrome P450 expression profile was determined in the MCF10A
human breast epithelial cell line, as was the ability of this cell
line to catalyze the bioactivation of the cooked food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
(PhIP). Using non-quantitative reverse transcription-polymerase chain
reaction (RT-PCR), transcripts for CYP1B1, CYP2J2, CYP2R1, CYP2U1,
CYP2W1, CYP4B1, CYP4F, CYP4V2, CYP4X1 and CYP4Z1 were detected in
both sub-confluent and confluent MCF10A cells. By contrast, CYP1A2
mRNA was detected only in confluent MCF10A cells, while CYP1A1, CYP2S1
and CYP2F1 were detected predominantly or exclusively in sub-confluent
cultures. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment of confluent
MCF10A cells markedly induced microsomal ethoxyresorufin O-deethylase
activity and CYP1A1, CYP1A2 and CYP1B1 mRNA levels, as determined
by real-time RT-PCR, while treatment with 10-4 M PhIP had little
effect on these P450 transcript levels. Treatment of confluent MCF10A
cells with PhIP (10-4 M) for 24, 48 or 72 h produced time-dependent
increases in the amounts of DNA adducts, as measured by 32P-post-labeling.
These results indicate that multiple P450s, including those known
to catalyze PhIP N-oxidation, are expressed in MCF10A cells, and
that this non-neoplastic human breast epithelial cell line contains
sufficient enzymatic machinery to support PhIP bioactivation and
generate DNA damage.},
issn = {0009-2797},
keywords = {PhIP, Heterocyclic amines, Cooked food mutagens, DNA adducts, Human
breast epithelial cells, CYP, P450, Breast carcinogenesis},
url = {http://www.sciencedirect.com/science/article/B6T56-4JF8HJH-1/2/038d53f425e3187c34b33d48cad562cc}
}
@ARTICLE{Thomas2007b,
author = {Thomas, Russell S. and Allen, Bruce C. and Nong, Andy and Yang, Longlong
and Bermudez, Edilberto and Clewell, Harvey J., III and Andersen,
Melvin E.},
title = {A Method to Integrate Benchmark Dose Estimates with Genomic Data
to Assess the Functional Effects of Chemical Exposure},
journal = {Toxicol. Sci.},
year = {2007},
volume = {98},
pages = {240--248},
number = {1},
month = jul,
abstract = {The use of genomic technology for assessing health risks associated
with chemical exposure has significant potential, but its direct
application has proven to be challenging for the toxicology and risk
assessment communities. In this study, a method was established for
analyzing dose-response microarray data using benchmark dose (BMD)
calculations and gene ontology (GO) classification. Gene expression
changes in the rat nasal epithelium following acute formaldehyde
exposure were used as a case study. The gene expression data were
first analyzed using a one-way ANOVA to identify genes that showed
significant dose-response behavior. These genes were then fit to
a series of four statistical models (linear, second-degree polynomial,
third-degree polynomial, and power models) and the least complex
model that best described the data was selected. The genes were matched
to their associated GO categories, and the average BMD and benchmark
dose lower confidence limit (BMDL) were calculated for each GO category.
The results were used to identify doses at which individual cellular
processes were altered. For the formaldehyde exposures, the BMD estimates
for the GO categories related to cell proliferation and DNA damage
were similar to those measured in previous studies using cell labeling
indices and DNA-protein cross-links and consistent with the BMD estimated
for rat nasal tumors. The method represents a significant advance
in applying genomic information to risk assessment by allowing a
comprehensive survey of molecular changes associated with chemical
exposure and providing the capability to identify reference doses
at which particular cellular processes are altered.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/98/1/240}
}
@ARTICLE{Thomas2009a,
author = {Thomas, Russell S. and Bao, Wenjun and Chu, Tzu-Ming and Bessarabova,
Marina and Nikolskaya, Tatiana and Nikolsky, Yuri and Andersen, Melvin
E. and Wolfinger, Russell D.},
title = {Use of Short-term Transcriptional Profiles to Assess the Long-term
Cancer-Related Safety of Environmental and Industrial Chemicals},
journal = {Toxicol. Sci.},
year = {2009},
volume = {112},
pages = {311--321},
number = {2},
month = dec,
abstract = {The process for evaluating chemical safety is inefficient, costly,
and animal intensive. There is growing consensus that the current
process of safety testing needs to be significantly altered to improve
efficiency and reduce the number of untested chemicals. In this study,
the use of short-term gene expression profiles was evaluated for
predicting the increased incidence of mouse lung tumors. Animals
were exposed to a total of 26 diverse chemicals with matched vehicle
controls over a period of 3 years. Upon completion, significant batch-related
effects were observed. Adjustment for batch effects significantly
improved the ability to predict increased lung tumor incidence. For
the best statistical model, the estimated predictive accuracy under
honest fivefold cross-validation was 79.3% with a sensitivity and
specificity of 71.4 and 86.3%, respectively. A learning curve analysis
demonstrated that gains in model performance reached a plateau at
25 chemicals, indicating that the size of current data set was sufficient
to provide a robust classifier. The classification results showed
that a small subset of chemicals contributed disproportionately to
the misclassification rate. For these chemicals, the misclassification
was more closely associated with genotoxicity status than with efficacy
in the original bioassay. Statistical models were also used to predict
dose-response increases in tumor incidence for methylene chloride
and naphthalene. The average posterior probabilities for the top
models matched the results from the bioassay for methylene chloride.
For naphthalene, the average posterior probabilities for the top
models overpredicted the tumor response, but the variability in predictions
was significantly higher. The study provides both a set of gene expression
biomarkers for predicting chemically induced mouse lung tumors and
a broad assessment of important experimental and analysis criteria
for developing microarray-based predictors of safety-related end
points.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/112/2/311}
}
@ARTICLE{Thomas2011a,
author = {Thomas, Russell S. and Clewell, Harvey J., III and Allen, Bruce C.
and Wesselkamper, Scott C. and Wang, Nina Ching Y. and Lambert, Jason
C. and Hess-Wilson, Janet K. and Zhao, Q. Jay and Andersen, Melvin
E.},
title = {Application of Transcriptional Benchmark Dose Values in Quantitative
Cancer and Noncancer Risk Assessment},
journal = {Toxicol. Sci.},
year = {2011},
volume = {120},
pages = {194--205},
number = {1},
month = mar,
abstract = {The traditional approach for estimating noncancer and cancer reference
values in quantitative chemical risk assessment is time and resource
intensive. The extent and nature of the studies required under the
traditional approach has limited the number of chemicals with published
risk assessments. In this study, female mice were exposed for 13
weeks to multiple concentrations of five chemicals that were positive
in a 2-year cancer bioassay. Traditional histological and organ weight
changes were evaluated, and gene expression microarray analysis was
performed on the target tissues. The histological, organ weight changes,
and the original tumor incidences in the original cancer bioassay
were analyzed using standard benchmark dose (BMD) methods to identify
noncancer and cancer points of departure, respectively. The dose-related
changes in gene expression were also analyzed using a BMD approach
and the responses grouped based on cellular biological processes.
A comparison of the transcriptional BMD values with those for the
traditional noncancer and cancer apical endpoints showed a high degree
of correlation for specific cellular biological processes. For chemicals
with human exposure data, the transcriptional BMD values were also
used to calculate a margin of exposure. The margins of exposure ranged
from 1900 to 54,000. Both the correlation between the BMD values
for the transcriptional and apical endpoints and the margin of exposure
analysis suggest that transcriptional BMD values may be used as potential
points of departure for noncancer and cancer risk assessment.},
comment = {10.1093/toxsci/kfq355},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/120/1/194}
}
@ARTICLE{Thomas2007c,
author = {Thomas, Russell S. and O'Connell, Thomas M. and Pluta, Linda and
Wolfinger, Russell D. and Yang, Longlong and Page, Todd J.},
title = {A Comparison of Transcriptomic and Metabonomic Technologies for Identifying
Biomarkers Predictive of Two-Year Rodent Cancer Bioassays},
journal = {Toxicol. Sci.},
year = {2007},
volume = {96},
pages = {40--46},
number = {1},
month = mar,
abstract = {Two-year rodent bioassays play a central role in evaluating the carcinogenic
potential of both commercial products and environmental contaminants.
The bioassays are expensive and time consuming, requiring years to
complete and costing $2-4 million. In this study, we compare transcriptomic
and metabonomic technologies for discovering biomarkers that can
efficiently and economically identify chemical carcinogens without
performing a standard two-year rodent bioassay. Animals were exposed
subchronically to two chemicals (one genotoxic and one nongenotoxic)
that were positive for lung and liver tumors in a standard two-year
bioassay, two chemicals that were negative, and two control groups.
Microarray analysis performed on liver and lung tissues identified
multiple biomarkers in each tissue that could discriminate between
carcinogenic and noncarcinogenic treatments. The discriminating biomarkers
shared a common expression profile among carcinogenic treatments
despite different genotoxicity categories and potential modes of
action, suggesting that they reflect underlying cellular changes
in the transition toward neoplasia. Statistical classification analysis
exhibited 100% accuracy in both tissues when the number of genes
was less than 5000. Additional genes reduced the predictive accuracy
of the model. Serum samples were analyzed by 1H nuclear magnetic
resonance (NMR) spectroscopy, and chemical-specific metabolites were
removed from the spectra. The statistical classification analysis
of the endogenous serum metabolites showed relatively low predictive
accuracy with few metabolites in the model, but the accuracy increased
to a maximum of 94% when all metabolites were added. These results
suggest that individual endogenous metabolites are relatively poor
biomarkers, but the metabolite profile as a whole is altered following
carcinogen treatment.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/96/1/40}
}
@ARTICLE{Thomas2007d,
author = {Thomas, Russell S. and Pluta, Linda and Yang, Longlong and Halsey,
Thomas A.},
title = {Application of Genomic Biomarkers to Predict Increased Lung Tumor
Incidence in 2-Year Rodent Cancer Bioassays},
journal = {Toxicol. Sci.},
year = {2007},
volume = {97},
pages = {55--64},
number = {1},
month = may,
abstract = {Rodent cancer bioassays are part of a legacy of safety testing that
has not changed significantly over the past 30 years. The bioassays
are expensive, time consuming, and use hundreds of animals. Fewer
than 1500 chemicals have been tested in a rodent cancer bioassay
compared to the thousands of environmental and industrial chemicals
that remain untested for carcinogenic activity. In this study, we
used existing data generated by the National Toxicology Program (NTP)
to identify gene expression biomarkers that can predict results from
a rodent cancer bioassay. A set of 13 diverse chemicals was selected
from those tested by the NTP. Seven chemicals were positive for increased
lung tumor incidence in female B6C3F1 mice and six were negative.
Female mice were exposed subchronically to each of the 13 chemicals,
and microarray analysis was performed on the lung. Statistical classification
analysis using the gene expression profiles identified a set of eight
probe sets corresponding to six genes whose expression correctly
predicted the increase in lung tumor incidence with 93.9% accuracy.
The sensitivity and specificity were 95.2 and 91.8%, respectively.
Among the six genes in the predictive signature, most were enzymes
involved in endogenous and xenobiotic metabolism, and one gene was
a growth factor receptor involved in lung development. The results
demonstrate that increases in chemically induced lung tumor incidence
in female mice can be predicted using gene biomarkers from a subchronic
exposure and may form the basis of a more efficient and economical
approach for evaluating the carcinogenic activity of chemicals.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/97/1/55}
}
@ARTICLE{Thomassen2007,
author = {Thomassen, Mads and Tan, Qihua and Eiriksdottir, Freyja and Bak,
Martin and Cold, Søren and Kruse, Torben A.},
title = {Prediction of metastasis from low-malignant breast cancer by gene
expression profiling},
journal = {Int. J. Cancer},
year = {2007},
volume = {120},
pages = {1070--1075},
number = {5},
abstract = {Abstract 10.1002/ijc.22449.abs Promising results for prediction of
outcome in breast cancer have been obtained by genome wide gene expression
profiling. Some studies have suggested that an extensive overtreatment
of breast cancer patients might be reduced by risk assessment with
gene expression profiling. A patient group hardly examined in these
studies is the low-risk patients for whom outcome is very difficult
to predict with currently used methods. These patients do not receive
adjuvant treatment according to the guidelines of the Danish Breast
Cancer Cooperative Group (DBCG). In this study, 26 tumors from low-risk
patients were examined with gene expression profiling. An intermediate
risk group of 34 low-malignant T2 tumors that fulfilled all other
low-risk criteria than tumor size was included to increase statistical
power. A 32-gene classifier, HUMAC32, was identified and it predicted
metastases with 80% sensitivity and 77% specificity. The classifier
was also validated in an independent group of high-risk tumors resulting
in comparable performance of HUMAC32 and a 70-gene classifier developed
for this group. Furthermore, the 70-gene signature was tested in
our low- and intermediate-risk samples. The results demonstrated
high cross-platform consistency of the classifiers. Higher performance
of HUMAC32 was demonstrated among the low-malignant cancers compared
with the 70-gene classifier. This suggests that although the metastatic
potential to some extend is determined by the same genes in groups
of tumors with different characteristics and risk, expression-based
classification specifically developed in low-risk patients have higher
predictive power in this group. © 2006 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {low risk, breast cancer, microarray, prognosis, meta-stasizing},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22449}
}
@ARTICLE{Thompson2005,
author = {Thompson, A. M.},
title = {Microarray technology for surgeons},
journal = {Br J Surg},
year = {2005},
volume = {92},
pages = {387--388},
number = {4},
abstract = {Abstract 10.1002/bjs.4958.abs Continuing the Journal's 2005 series
of leading articles highlighting areas where laboratory science meets
clinical practice, Professor Alastair Thompson of Dundee outlines
the present and future prospects for microarray technology. Copyright
© 2005 British Journal of Surgery Society Ltd. Published by John
Wiley & Sons, Ltd.},
issn = {1365-2168},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/bjs.4958}
}
@ARTICLE{Thompson2008,
author = {Thompson, Colin A. and Burcham, Philip C.},
title = {Genome-Wide Transcriptional Responses to Acrolein},
journal = {Chemical Research in Toxicology},
year = {2008},
volume = {21},
pages = {2245-2256},
number = {12},
doi = {10.1021/tx8001934},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx8001934},
url = {http://pubs.acs.org/doi/abs/10.1021/tx8001934}
}
@ARTICLE{Thompson2005a,
author = {Thompson, Christopher J. and Ross, Susan M. and Hensley, Janan and
Liu, Kejun and Heinze, Susanna C. and Young, S. Stanley and Gaido,
Kevin W.},
title = {Differential Steroidogenic Gene Expression in the Fetal Adrenal Gland
Versus the Testis and Rapid and Dynamic Response of the Fetal Testis
to Di(n-butyl) Phthalate},
journal = {Biol Reprod},
year = {2005},
volume = {73},
pages = {908--917},
number = {5},
month = nov,
abstract = {The phthalate ester di(n-butyl) phthalate (DBP) causes feminization
of male rats upon in utero exposure by repressing expression of genes
required for testicular steroidogenesis. Previous work in our laboratory
has shown that repression of gene expression and steroidogenesis
in the fetal testis is apparent within a few hours of DBP exposure.
The purpose of this study was to determine the precise timing of
DBP-associated gene expression changes in the fetal testis using
transcriptional profiling and to determine whether DBP exerts similar
effects on steroidogenesis in the fetal adrenal. A DBP time-course
experiment showed that testicular steroidogenesis was decreased within
1 h of DBP exposure and that this decrease preceded the repressed
transcription of Star (steroidogenic acute regulatory protein); Scarb1
(scavenger receptor class B, member 1; also know as Sr-b1); Cyp11a1
(cytochrome P450, family 11, subfamily a, polypeptide 1; also known
as P450SCC); and Cyp17a1 (cytochrome P450 family 17, subfamily a,
polypeptide 1; also known as Cyp17). Gene expression profiling demonstrated
rapid (within 1 to 3 h) and transient induction of immediate early
genes in the fetal testis after administration of DBP to the pregnant
dam. There was a statistically insignificant decrease in corticosterone
production by the fetal adrenal after in utero exposure to DBP from
Gestation Day 12 to Gestation Day 19. The extent of steroidogenesis
diminution was much less in the adrenal than in the testis (approximately
45% decrease in the adrenal versus 87% decrease in the testis) and
expression of genes required for steroidogenesis in the adrenal was
unaffected by DBP. Together, these studies demonstrate that DBP initiates
a rapid and dynamic change in gene expression in the fetal testis
that likely plays a role in the reduction in steroidogenesis that
is unique to the fetal testis relative to the steroidogenically active
fetal adrenal.},
url = {http://www.biolreprod.org/cgi/content/abstract/73/5/908}
}
@ARTICLE{Thompson2010,
author = {Thompson, Dylan and Markovitch, Daniella and Betts, James A. and
Mazzatti, Dawn and Turner, James and Tyrrell, Rex M.},
title = {Time course of changes in inflammatory markers during a 6-mo exercise
intervention in sedentary middle-aged men: a randomized-controlled
trial},
journal = {J Appl Physiol},
year = {2010},
volume = {108},
pages = {769--779},
number = {4},
month = apr,
abstract = {Regular exercise may improve systemic markers of chronic inflammation,
but direct evidence and dose-response information is lacking. The
objective of this study was to examine the effect and time course
of changes in markers of chronic inflammation in response to progressive
exercise training (and subsequent detraining). Forty-one sedentary
men 45-64 yr of age completed either a progressive 24-wk exercise
intervention or control followed by short-term removal of the intervention
(2-wk detraining). Serum IL-6 fell by -0.4 pg/ml (SD 0.6) after 12
wk and responded to moderate-intensity exercise. Serum alanine aminotransferase
(ALT) activity fell -7 U/l (SD 11) at 24 wk although there was no
evidence of any change by week 12 (and therefore ALT required more
vigorous-intensity activity and/or a more prolonged intervention).
The effect on IL-6 was lost after 2-wk detraining whereas the change
in ALT was retained. The temporal fall and rise in IL-6 with training
and subsequent detraining in men with high IL-6 at baseline provided
a retrospective opportunity to examine parallel genomic changes in
peripheral mononuclear cells. A subset of 53 probes was differentially
regulated by at least twofold after training with 31 of these changes
being lost after detraining (n = 6). IL-6 responded quickly to the
carefully monitored exercise intervention (within weeks) and required
only moderate-intensity exercise, whereas ALT took longer to change
and/or required more vigorous-intensity exercise. Further work is
required to determine whether any of the genes that temporally changed
in parallel with changes in IL-6 are a cause or consequence of this
response.},
url = {http://jap.physiology.org/cgi/content/abstract/108/4/769}
}
@BOOK{Thompson2008a,
title = {Sources of Variability in Toxicogenomic Assays},
publisher = {John Wiley \& Sons, Ltd},
year = {2008},
author = {Thompson, Karol and Pine, P. Scott and Rosenzweig, Barry},
pages = {101--109},
abstract = {Summary 10.1002/9780470699638.ch5.abs This chapter contains sections
titled:},
booktitle = {Toxicogenomics},
issn = {9780470699638},
keywords = {toxicogenomic assay and source variability, Kyoto Encyclopedia of
Genes and Genomes (KEGG) pathways, Microarray Quality Control (MAQC)
Consortium, HESI Technical Committee and doxorubicin cardiotoxicity,
RNA integrity effect and microarray data sensitivity, toxicogenomic
study design RNA quality threshold, signal uniformity across array
assessment},
url = {http://dx.doi.org/10.1002/9780470699638.ch5}
}
@ARTICLE{Thompson2005b,
author = {Thompson, Karol L. and Rosenzweig, Barry A. and Pine, P. Scott and
Retief, Jacques and Turpaz, Yaron and Afshari, Cynthia A. and Hamadeh,
Hisham K. and Damore, Michael A. and Boedigheimer, Michael and Blomme,
Eric and Ciurlionis, Rita and Waring, Jeffrey F. and Fuscoe, James
C. and Paules, Richard and Tucker, Charles J. and Fare, Thomas and
Coffey, Ernest M. and He, Yudong and Collins, Patrick J. and Jarnagin,
Kurt and Fujimoto, Susan and Ganter, Brigitte and Kiser, Gretchen
and Kaysser-Kranich, Tamma and Sina, Joseph and Sistare, Frank D.},
title = {Use of a mixed tissue RNA design for performance assessments on multiple
microarray formats},
journal = {Nucleic Acids Res.},
year = {2005},
volume = {33},
pages = {e187--},
number = {22},
month = dec,
abstract = {The comparability and reliability of data generated using microarray
technology would be enhanced by use of a common set of standards
that allow accuracy, reproducibility and dynamic range assessments
on multiple formats. We designed and tested a complex biological
reagent for performance measurements on three commercial oligonucleotide
array formats that differ in probe design and signal measurement
methodology. The reagent is a set of two mixtures with different
proportions of RNA for each of four rat tissues (brain, liver, kidney
and testes). The design provides four known ratio measurements of
>200 reference probes, which were chosen for their tissue-selectivity,
dynamic range coverage and alignment to the same exemplar transcript
sequence across all three platforms. The data generated from testing
three biological replicates of the reagent at eight laboratories
on three array formats provides a benchmark set for both laboratory
and data processing performance assessments. Close agreement with
target ratios adjusted for sample complexity was achieved on all
platforms and low variance was observed among platforms, replicates
and sites. The mixed tissue design produces a reagent with known
gene expression changes within a complex sample and can serve as
a paradigm for performance standards for microarrays that target
other species.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/33/22/e187}
}
@ARTICLE{Thompson2007,
author = {Thompson, Nichola M. and Norman, Amy M. and Donkin, Shawn S. and
Shankar, Ravi R. and Vickers, Mark H. and Miles, Jennifer L. and
Breier, Bernhard H.},
title = {Prenatal and Postnatal Pathways to Obesity: Different Underlying
Mechanisms, Different Metabolic Outcomes},
journal = {Endocrinology},
year = {2007},
volume = {148},
pages = {2345--2354},
number = {5},
month = may,
abstract = {Obesity and type 2 diabetes are worldwide health issues. The present
paper investigates prenatal and postnatal pathways to obesity, identifying
different metabolic outcomes with different effects on insulin sensitivity
and different underlying mechanisms involving key components of insulin
receptor signaling pathways. Pregnant Wistar rats either were fed
chow ad libitum or were undernourished throughout pregnancy, generating
either control or intrauterine growth restricted (IUGR) offspring.
Male offspring were fed either standard chow or a high-fat diet from
weaning. At 260 d of age, whole-body insulin sensitivity was assessed
by hyperinsulinemic-euglycemic clamp, and other metabolic parameters
were measured. As expected, high-fat feeding caused diet-induced
obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity
of IUGR offspring was similar to that of control offspring, despite
fasting insulin hypersecretion and increased adiposity, irrespective
of postnatal nutrition. Real-time PCR and Western blot analyses of
key markers of insulin sensitivity and metabolic regulation showed
that IUGR offspring had increased hepatic levels of atypical protein
kinase C {zeta} (PKC {zeta}) and increased expression of fatty acid
synthase mRNA. In contrast, DIO led to decreased expression of fatty
acid synthase mRNA and hepatic steatosis. The decrease in hepatic
PKC {zeta} with DIO may explain, at least in part, the insulin resistance.
Our data suggest that the mechanisms of obesity induced by prenatal
events are fundamentally different from those of obesity induced
by postnatal high-fat nutrition. The origin of insulin hypersecretion
in IUGR offspring may be independent of the mechanistic events that
trigger the insulin resistance commonly observed in DIO.},
url = {http://endo.endojournals.org/cgi/content/abstract/148/5/2345}
}
@ARTICLE{Thompson2010b,
author = {Thompson, Reid F. and Fazzari, Melissa J. and Greally, John M.},
title = {Experimental approaches to the study of epigenomic dysregulation
in ageing},
journal = {Experimental Gerontology},
year = {2010},
volume = {45},
pages = {255--268},
number = {4},
month = apr,
abstract = {In this review, we describe how normal ageing may involve the acquisition
of epigenetic errors over time, akin to the accumulation of genetic
mutations with ageing. We describe how such experiments are currently
performed, their limitations technically and analytically and their
application to ageing research.},
booktitle = {Special Issue: Epigenetic Mechanisms of Aging and Age-related Diseases},
issn = {0531-5565},
keywords = {Epigenetic, DNA methylation, Chromatin, Aging, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T6J-4Y4DDS6-1/2/4ff2fe30ecfc11aaca8c2cd058df0a8f}
}
@ARTICLE{Thompson2010a,
author = {Thompson, Reid F. and Fazzari, Melissa J. and Niu, Hongshun and Barzilai,
Nir and Simmons, Rebecca A. and Greally, John M.},
title = {Experimental Intrauterine Growth Restriction Induces Alterations
in DNA Methylation and Gene Expression in Pancreatic Islets of Rats},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {15111--15118},
number = {20},
month = may,
abstract = {Intrauterine growth restriction (IUGR) increases susceptibility to
age-related diseases, including type 2 diabetes (T2DM), and is associated
with permanent and progressive changes in gene expression. Our study
was designed to test whether epigenomic dysregulation mediates the
cellular memory of this intrauterine event. To test this hypothesis,
we isolated pancreatic islets from control and IUGR (induced by bilateral
uterine artery ligation at day 18 of fetal life) animals at 7 weeks
of age. Using the HELP (HpaII tiny fragment enrichment by ligation-mediated
PCR) assay, we generated the first DNA methylation map at almost
1 million unique sites throughout the rat genome in normal pancreatic
islet cells, allowing us to identify the changes that occur as a
consequence of IUGR. We validated candidate dysregulated loci with
quantitative assays of cytosine methylation and gene expression.
IUGR changes cytosine methylation at [~]1,400 loci (false discovery
rate of 4.2%) in male rats at 7 weeks of age, preceding the development
of diabetes and thus representing candidate loci for mediating the
pathogenesis of metabolic disease that occurs later in life. Epigenetic
dysregulation occurred preferentially at conserved intergenic sequences,
frequently near genes regulating processes known to be abnormal in
IUGR islets, such as vascularization, {beta}-cell proliferation,
insulin secretion, and cell death, associated with concordant changes
in mRNA expression. These results demonstrate that epigenetic dysregulation
is a strong candidate for propagating the cellular memory of intrauterine
events, causing changes in expression of nearby genes and long term
susceptibility to type 2 diabetes.},
url = {http://www.jbc.org/cgi/content/abstract/285/20/15111}
}
@ARTICLE{Thorell2009,
author = {Thorell, Kaisa and Bergman, Annika and Carén, Helena and Nilsson,
Staffan and Kogner, Per and Martinsson, Tommy and Abel, Frida},
title = {Verification of genes differentially expressed in neuroblastoma tumours:
a study of potential tumour suppressor genes},
journal = {BMC Medical Genomics},
year = {2009},
volume = {2},
pages = {53},
number = {1},
abstract = {BACKGROUND:One of the most striking features of the childhood malignancy
neuroblastoma (NB) is its clinical heterogeneity. Although there
is a great need for better clinical and biological markers to distinguish
between tumours with different severity and to improve treatment,
no clear-cut prognostic factors have been found. Also, no major NB
tumour suppressor genes have been identified.METHODS:In this study
we performed expression analysis by quantitative real-time PCR (QPCR)
on primary NB tumours divided into two groups, of favourable and
unfavourable outcome respectively. Candidate genes were selected
on basis of lower expression in unfavourable tumour types compared
to favourables in our microarray expression analysis. Selected genes
were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA)
targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes
were selected from the TLDA analysis for verification using individual
TaqMan assays in a new set of 13 NB tumour samples.RESULTS:By TLDA
analysis, 81 out of 87 genes were found to be significantly differentially
expressed between groups, of which 14 have previously been reported
as having an altered gene expression in NB. In the second verification
round, seven out of 12 transcripts showed significantly lower expression
in unfavourable NB tumours, ATBF1, CACNA2D3, CNTNAP2, FUSIP1, GNB1,
SLC35E2, and TFAP2B. The gene that showed the highest fold change
in the TLDA analysis, POU4F2, was investigated for epigenetic changes
(CpG methylation) and mutations in order to explore the cause of
the differential expression. Moreover, the fragile site gene CNTNAP2
that showed the largest fold change in verification group 2 was investigated
for structural aberrations by copy number analysis. However, the
analyses of POU4F2 and CNTNAP2 showed no genetic alterations that
could explain a lower expression in unfavourable NB tumours.CONCLUSION:Through
two steps of verification, seven transcripts were found to significantly
discriminate between favourable and unfavourable NB tumours. Four
of the transcripts, CACNA2D3, GNB1, SLC35E2, and TFAP2B, have been
observed in previous microarray studies, and are in this study independently
verified. Our results suggest these transcripts to be markers of
malignancy, which could have a potential usefulness in the clinic.},
doi = {10.1186/1755-8794-2-53},
issn = {1755-8794},
pubmedid = {19686582},
url = {http://www.biomedcentral.com/1755-8794/2/53}
}
@ARTICLE{Thormann2001,
author = {Thormann, Wolfgang and Lurie, Ira S. and McCord, Bruce and Marti,
Ulrich and Cenni, Bruno and Malik, Naseem},
title = {Advances of capillary electrophoresis in clinical and forensic analysis
(1999–2000)},
journal = {ELECTROPHORESIS},
year = {2001},
volume = {22},
pages = {4216--4243},
number = {19},
abstract = {Abstract 10.1002/1522-2683(200111)22:19<4216::AID-ELPS4216>3.3.CO;2-N
In this paper, capillary electrophoresis in clinical and forensic
analysis is reviewed on the basis of the literature of 1999, 2000
and the first papers in 2001. An overview of progress and relevant
examples for each major field of application, namely (i) analysis
of drug seizures, explosives residues, gunshot residues and inks,
(ii) monitoring of drugs, endogenous small molecules and ions in
biofluids and tissues, (iii) general screening for serum proteins
and analysis of specific proteins (carbohydrate deficient transferrin,
α1-antitrypsin, lipoproteins and hemoglobins) in biological fluids,
and (iv) analysis of nucleic acids and oligonucleotides in biological
samples, including oligonucleotide therapeutics, are presented.},
issn = {1522-2683},
keywords = {Capillary electrophoresis, Clinical analysis, Forensic analysis, Review},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/1522-2683(200111)22:19<4216::AID-ELPS4216>3.0.CO;2-W}
}
@ARTICLE{Thorn2009,
author = {Thorn, C C and Freeman, T C and Scott, N and Guillou, P J and Jayne,
D G},
title = {Laser microdissection expression profiling of marginal edges of colorectal
tumours reveals evidence of increased lactate metabolism in the aggressive
phenotype},
journal = {Gut},
year = {2009},
volume = {58},
pages = {404--412},
number = {3},
month = mar,
abstract = {BackgroundThe morphology of the invasive margin in colorectal cancer
can be described as either pushing or infiltrative. These phenotypes
carry prognostic significance, particularly in node negative disease,
and provide an excellent model for the study of invasive behaviour
in vivo. MethodsThe marginal edges of 16 stage-matched tumours exhibiting
these contrasting growth patterns were microdissected. The extracted
mRNA was amplified and hybridised to a 9546 feature oligonucleotide
array. Selected differentials were validated using real-time polymerase
chain reaction and the protein product was interrogated by using
immunohistochemistry. ResultsAfter stringent quality control and
filtering of data generated, 39 genes were identified as being significantly
differentially expressed between the two types of marginal edge.
Several genes involved in cellular metabolism were identified as
differentials including lactate dehydrogenase B (LDHB) and modulators
of glucose transport. ConclusionsThe LDH expression profile differs
between the invasive phenotypes. A hypothesis is proposed in which
altered metabolism is a cause of contrasting invasive behaviour independent
of the hypoxia-inducible factor mediated hypoxic response, consistent
with the Warburg phenomenon.},
url = {http://gut.bmj.com/cgi/content/abstract/58/3/404}
}
@ARTICLE{Thorn2005,
author = {Thorn, I and Olsson-Stromberg, U and Ohlsen, C and Jonsson, AM and
Klangby, U and Simonsson, B and Barbany, G},
title = {The impact of RNA stabilization on minimal residual disease assessment
in chronic myeloid leukemia},
journal = {Haematologica},
year = {2005},
volume = {90},
pages = {1471--1476},
number = {11},
month = nov,
abstract = {BACKGROUND AND OBJECTIVES: Accurate quantification of BCR-ABL mRNA
is of critical importance for managing patients with chronic myeloid
leukemia (CML) who are receiving imatinib therapy. RNA degradation
thus constitutes a potential problem for laboratories quantifying
minimal residual disease (MRD). Patients' samples that take a long
time to be transported from the hospital to the analyzing laboratory
may be subject to RNA degradation with a corresponding loss in sensitivity
and possible generation of false negative results. Recently, RNA
preservation systems have been developed in order to improve RNA
stability. The aim of the present study was to investigate such a
system. DESIGN AND METHODS: We evaluated the performance of the PAXgene
Blood RNA Kit in follow-up CML peripheral blood samples and compared
the results to those from unstabilized parallel Trizol extracted
samples. The different sample processing methods were evaluated by
real-time polymerase chain reaction (PCR) analysis. RESULTS: RNA
isolated with the PAXgene system gave a superior yield per milliliter
of blood than did the routine Trizol extraction method. However,
although of comparable quality, the RNA did not PCR-amplify as efficiently
as equal amounts of RNA from routinely processed samples. Therefore,
RNA processed with the PAXgene system showed decreased sensitivity
for MRD detection, resulting in false negative results. The sensitivity
was comparable to that of samples processed routinely 20-30 hours
after phlebotomy. INTERPRETATION AND CONCLUSIONS: We conclude that
routinely processed, i.e. unstabilized, peripheral blood that reaches
the laboratory and is processed within 30 hours is preferable for
MRD detection. Optimal results were achieved with fresh samples processed
within 5 hours with the Trizol method. However, RNA stabilization
may be useful if sample transit is expected to exceed 30 hours.},
url = {http://www.haematologica.org/cgi/content/abstract/90/11/1471}
}
@ARTICLE{Thorn2007,
author = {Thorn, S.R. and Meyer, M.J. and Van Amburgh, M.E. and Boisclair,
Y.R.},
title = {Effect of Estrogen on Leptin and Expression of Leptin Receptor Transcripts
in Prepubertal Dairy Heifers},
journal = {Journal of Dairy Science},
year = {2007},
volume = {90},
pages = {3742--3750},
number = {8},
month = aug,
abstract = {Plasma leptin concentrations increase as growing dairy heifers approach
puberty and have greater plasma estrogen. In intact and ovariectomized
rodents, estrogen has been shown to modulate expression of leptin
and its receptor (Ob-R). To determine if estrogen regulates the bovine
leptin system, prepubertal dairy heifers were ovariectomized at 140
d of age or left intact. A month later, both groups received a subcutaneous
injection of excipient or 17[beta]-estradiol for 3 consecutive days.
Neither ovarian status nor 17[beta]-estradiol injection altered plasma
leptin or leptin mRNA abundance in adipose tissue depots. To assess
whether these factors affected Ob-R expression, we tested 20 bovine
tissues for leptin receptor (Ob-R) by using quantitative real-time
PCR assays for the short receptor isoform (Ob-Ra), the long receptor
isoform (Ob-Rb), and all receptor isoforms (Ob-RTOTAL). Ob-RTOTAL
was detected in all tissues, with copy numbers covering 3 orders
of magnitude between the lowest and highest expressing tissues (kidney
cortex vs. liver). The Ob-Rb isoform accounted for 40% of Ob-RTOTAL
in the hypothalamus, but averaged less than 3% of Ob-RTOTAL in peripheral
tissues. Reciprocally, Ob-Ra accounted for only 19% of Ob-RTOTAL
in the hypothalamus and for nearly all of Ob-RTOTAL in most peripheral
tissues. Finally, we evaluated the effects of ovarian status and
17[beta]-estradiol on Ob-R expression in selected tissues. Treatment
with 17[beta]-estradiol reduced Ob-RTOTAL, Ob-Rb, and Ob-Ra expression
by 70% in the uterine endometrium and tended to do the same in mammary
adipose tissue. There was no effect of 17[beta]-estradiol on Ob-R
in the hypothalamus, liver, soleus muscle, or subcutaneous adipose
tissue. We conclude that greater estrogen secretion does not cause
increased plasma leptin in prepubertal dairy heifers but estradiol
can modulate Ob-R expression in some estrogen-responsive tissues.},
issn = {0022-0302},
keywords = {spatial, hypothalamus, uterus, mammary gland},
url = {http://www.sciencedirect.com/science/article/B9887-4YDKGYM-T/2/1008727c2dd94bfea55c999296bc5f8f}
}
@ARTICLE{Thorn2008,
author = {Thorn, Stephanie R. and Ehrhardt, Richard A. and Butler, W. Ronald
and Quirk, Susan M. and Boisclair, Yves R.},
title = {Insulin regulates hepatic leptin receptor expression in early lactating
dairy cows},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2008},
volume = {295},
pages = {R1455--1462},
number = {5},
month = nov,
abstract = {Energy balance controls the expression of the leptin receptor (Lepr)
in the ruminant hypothalamus but whether similar regulation occurs
in peripheral tissues is unknown. To address this issue, we measured
Lepr expression in the liver and adipose tissue of dairy cows during
the transition from late pregnancy (LP) to early lactation (EL).
This period is characterized by the development of a profound state
of energy insufficiency and is associated with reduced plasma insulin
and leptin and with increased plasma growth hormone. Hepatic expression
of the short (Lepr-a) and long (Lepr-b) isoforms was 40% higher during
EL (8 days postpartum) than LP (30 days prepartum). A similar effect
was observed when negative energy balance was induced in nonpregnant,
late-lactation dairy cows by food restriction, implicating energy
insufficiency as a specific cause in EL. The stimulation of hepatic
Lepr expression was reversed after a 48-h period of hyperinsulinemic
euglycemia in EL. Changes in hepatic Lepr expression during chronic
elevation of plasma leptin in EL or plasma growth hormone in nonpregnant,
late-lactation cows did not support a role for these hormones in
mediating the effects of energy insufficiency on hepatic Lepr expression.
In adipose tissue, Lepr expression was increased 10-fold during the
transition from LP to EL. Overall, these data indicate that hypoinsulinemia
is partly responsible for the induction of Lepr expression in the
liver, and perhaps adipose tissue, of energy-deficient dairy cows.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/295/5/R1455}
}
@ARTICLE{Thorn2010,
author = {Thorn, Stephanie R. and Giesy, Sarah L. and Myers, Martin G., Jr.
and Boisclair, Yves R.},
title = {Mammary Ductal Growth Is Impaired in Mice Lacking Leptin-Dependent
Signal Transducer and Activator of Transcription 3 Signaling},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {3985--3995},
number = {8},
month = aug,
abstract = {Mice lacking leptin (ob/ob) or its full-length receptor (db/db) are
obese and reproductively incompetent. Fertility, pregnancy, and lactation
are restored, respectively, in ob/ob mice treated with leptin through
mating, d 6.5 post coitum, and pregnancy. Therefore, leptin signaling
is needed for lactation, but the timing of its action and the affected
mammary process remain unknown. To address this issue, we used s/s
mice lacking only leptin-dependent signal transducer and activator
of transcription (STAT)3 signaling. These mice share many features
with db/db mice, including obesity, but differ by retaining sufficient
activity of the hypothalamic-pituitary-ovarian axis to support reproduction.
The s/s mammary epithelium was normal at 3 wk of age but failed to
expand through the mammary fat pad (MFP) during the subsequent pubertal
period. Ductal growth failure was not corrected by estrogen therapy
and did not relate to inadequate IGF-I production by the MFP or to
the need for epithelial or stromal leptin-STAT3 signaling. Ductal
growth failure coincided with adipocyte hypertrophy and increased
MFP production of leptin, TNF{alpha}, and IL6. These cytokines, however,
were unable to inhibit the proliferation of a collection of mouse
mammary epithelial cell lines. In conclusion, the very first step
of postnatal mammary development fails in s/s mice despite sufficient
estrogen IGF-I and an hypothalamic-pituitary-ovarian axis capable
of supporting reproduction. This failure is not caused by mammary
loss of leptin-dependent STAT3 signaling or by the development of
inflammation. These data imply the existence of an unknown mechanism
whereby leptin-dependent STAT3 signaling and obesity alter mammary
ductal development.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/8/3985}
}
@ARTICLE{Thornburg2010,
author = {Thornburg, Natalie J. and Shepherd, Bryan and Crowe, James E., Jr.},
title = {Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal
Immune Responses following Respiratory Syncytial Virus Infection},
journal = {J. Virol.},
year = {2010},
volume = {84},
pages = {12895--12902},
number = {24},
month = dec,
abstract = {Respiratory syncytial virus (RSV) is a major cause of morbidity and
mortality. Previous studies have suggested that T-cell responses
may contribute to RSV immunopathology, which could be driven by dendritic
cells (DCs). DCs are productively infected by RSV, and during RSV
infections, there is an increase of DCs in the lungs with a decrease
in the blood. Pediatric populations are particularly susceptible
to severe RSV infections; however, DC responses to RSV from pediatric
populations have not been examined. In this study, primary isolated
DCs from cord blood and adult peripheral blood were compared after
RSV infection. Transcriptional profiling and biological network analysis
identified transforming growth factor beta (TGF-{beta}) and associated
signaling molecules as differentially regulated in the two age groups.
TGF-{beta}1 was decreased in RSV-infected adult-blood DCs but increased
in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs
with autologous T cells induced secretion of gamma interferon (IFN-{gamma}),
interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha
(TNF-{alpha}). Conversely, coculture of cord RSV-infected DCs and
autologous T cells induced secretion of IL-4, IL-6, IL-1{beta}, and
IL-17. Addition of purified TGF-{beta}1 to adult DC-T-cell cocultures
reduced secretion of IFN-{gamma}, IL-12p70, IL-2, and TNF-{alpha},
while addition of a TGF-{beta} chemical inhibitor to cord DC-T-cell
cocultures increased secretion of IL-12p70. These data suggest that
TGF-{beta} acts as a major regulator of RSV DC-T-cell responses,
which could contribute to immunopathology during infancy.},
comment = {10.1128/JVI.01273-10},
url = {http://jvi.asm.org/cgi/content/abstract/84/24/12895}
}
@ARTICLE{Thornburg2010a,
author = {Thornburg, Natalie J. and Shepherd, Bryan and Crowe, James E., Jr.},
title = {TGF-{beta} is a major regulator of neonatal human immune responses
following respiratory syncytial virus infection},
journal = {J. Virol.},
year = {2010},
pages = {JVI.01273-10--},
month = oct,
abstract = {Respiratory syncytial virus (RSV) is a major cause of morbidity and
mortality. Previous studies have suggested that T cell responses
may contribute to RSV immunopathology, which could be driven by dendritic
cells (DCs). DCs are productively infected by RSV, and during RSV
infections, there is an increase of DCs in the lungs with a decrease
in the blood. Pediatric populations are particularly susceptible
to severe RSV infections, however DC responses to RSV from pediatric
populations have not been examined. In this study, primary isolated
DCs from cord blood and adult peripheral blood were compared after
RSV-infection. Transcriptional profiling and biological network analysis
identified transforming growth factor (TGF)-{beta} and associated
signaling molecules as differentially regulated in the two age groups.
TGF-{beta}1 was decreased in RSV-infected adult blood DCs, but increased
in RSV-infected cord blood DCs. Co-culture of adult RSV-infected
DCs with autologous T-cells induced secretion of interferon gamma
(IFN{gamma}), IL-12p70, IL-2, and tumor necrosis factor alpha (TNF{alpha}).
Conversely, co-culture of cord RSV-infected DCs and autologous T-cells
induced secretion of IL-4, IL-6, IL-1{beta}, and IL-17. Addition
of purified TGF-{beta}1 to adult DC-T cell co-cultures reduced secretion
of IFN{gamma}, IL-12p70, IL-2, and TNF{alpha}, which addition of
a TGF-{beta} chemical inhibitor to cord DC-T cell co-cultures increased
secretion of IL-12p70. These data suggest that TGF-{beta} acts as
a major regulator of RSV DC-T cell responses, which could contribute
to immunopathology during infancy.},
url = {http://jvi.asm.org/cgi/content/abstract/JVI.01273-10v1}
}
@ARTICLE{Thornley2011,
author = {Jessica A. Thornley and Heidi W. Trask and Christian J.A. Ridley
and Murray Korc and Jiang Gui and Carol S. Ringelberg and Sinny Wang
and Craig R. Tomlinson},
title = {Differential regulation of polysome mRNA levels in mouse Hepa-1C1C7
cells exposed to dioxin},
journal = {Toxicology in Vitro},
year = {2011},
volume = {25},
pages = {1457 - 1467},
number = {7},
abstract = {The environmental agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD
or dioxin) causes a multitude of human illnesses. In order to more
fully understand the underlying biology of TCDD toxicity, we tested
the hypothesis that new candidate genes could be identified using
polysome RNA from TCDD-treated mouse Hepa-1c1c7 cells. We found that
(i) differentially expressed whole cell and cytoplasm RNA levels
are both poor predictors of polysome RNA levels; (ii) for a majority
of RNAs, differential RNA levels are regulated independently in the
nucleus, cytoplasm, and polysomes; (iii) for the remaining polysome
RNAs, levels are regulated via several different mechanisms, including
a “tagging� of mRNAs in the nucleus for immediate polysome entry;
and (iv) most importantly, a gene list derived from differentially
expressed polysome RNA generated new genes and cell pathways potentially
related to TCDD biology.},
doi = {10.1016/j.tiv.2011.04.020},
issn = {0887-2333},
keywords = {Polysomes},
url = {http://www.sciencedirect.com/science/article/pii/S0887233311001160}
}
@ARTICLE{Thorrez2011,
author = {Thorrez, Lieven and Laudadio, Ilaria and Van Deun, Katrijn and Quintens,
Roel and Hendrickx, Nico and Granvik, Mikaela and Lemaire, Katleen
and Schraenen, Anica and Van Lommel, Leentje and Lehnert, Stefan
and Aguayo-Mazzucato, Cristina and Cheng-Xue, Rui and Gilon, Patrick
and Van Mechelen, Iven and Bonner-Weir, Susan and Lemaigre, Frederic
and Schuit, Frans},
title = {Tissue-specific disallowance of housekeeping genes: The other face
of cell differentiation},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {95--105},
number = {1},
month = jan,
abstract = {We report on a hitherto poorly characterized class of genes that are
expressed in all tissues, except in one. Often, these genes have
been classified as housekeeping genes, based on their nearly ubiquitous
expression. However, the specific repression in one tissue defines
a special class of "disallowed genes." In this paper, we used the
intersection-union test to screen for such genes in a multi-tissue
panel of genome-wide mRNA expression data. We propose that disallowed
genes need to be repressed in the specific target tissue to ensure
correct tissue function. We provide mechanistic data of repression
with two metabolic examples, exercise-induced inappropriate insulin
release and interference with ketogenesis in liver. Developmentally,
this repression is established during tissue maturation in the early
postnatal period involving epigenetic changes in histone methylation.
In addition, tissue-specific expression of microRNAs can further
diminish these repressed mRNAs. Together, we provide a systematic
analysis of tissue-specific repression of housekeeping genes, a phenomenon
that has not been studied so far on a genome-wide basis and, when
perturbed, can lead to human disease.},
comment = {10.1101/gr.109173.110},
url = {http://genome.cshlp.org/cgi/content/abstract/21/1/95}
}
@ARTICLE{Thorsen2006,
author = {Thorsen, Jim and Høyheim, Bjørn and Koppang, Erling O.},
title = {Isolation of the Atlantic salmon tyrosinase gene family reveals heterogenous
transcripts in a leukocyte cell line},
journal = {Pigment Cell Research},
year = {2006},
volume = {19},
pages = {327--336},
number = {4},
abstract = {Summary In ectothermic vertebrates, visceral organs harbor melanin-containing
cells. Their ability as pigment producers is nevertheless disputed.
To address expression of the key genes for melanogenesis in Atlantic
salmon (Salmo salar), a tyrosinase-positive leukocyte cell line (SHK-1)
and skin were used to obtain full-length tyrosinase (Tyr), tyrosinase-like
protein-1 (Tyrp1), and dopachrome tautomerase (Dct) mRNA transcripts.
In the SHK-1 cells, two different Tyrp1 transcripts were identified,
one lacking exon 1. However, only the full-length version of Tyrp1
was identified in the skin. Sequencing of Tyrp1 genomic region revealed
that the two Tyrp1 transcripts might originate from two different
loci, possibly a result of pseudo-tetraploidity of the Atlantic salmon
genome. Expression of Tyr, Tyrp1 and Dct was investigated by quantitative
real-time reverse transcriptase polymerase cain reaction showing
highest expression in the SHK-1 cell line and skin, intermediate
in pronephros, and negligible or absent in liver and muscle. Histological
approaches were used to demonstrate melanin and revealed presence
of melanized cells in skin, kidney and liver, and absence of such
cells in muscle. In addition to verify melanin synthesis abilities
of visceral-located cells, our results indicate loci-specific transcription
differences between populations of melanin-producing cells in Atlantic
salmon.},
issn = {1600-0749},
keywords = {Atlantic salmon, Dct, leukocyte, melanogenesis, melanomacrophage,
tyrosinase, Tyrp1},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0749.2006.00319.x}
}
@ARTICLE{Thorsen2011a,
author = {Thorsen, Kasper and Mansilla, Francisco and Schepeler, Troels and
Oster, Bodil and Rasmussen, Mads H. and Dyrskjot, Lars and Karni,
Rotem and Akerman, Martin and Krainer, Adrian R. and Laurberg, Soren
and Andersen, Claus L. and Orntoft, Torben F.},
title = {Alternative Splicing of SLC39A14 in Colorectal Cancer is Regulated
by the Wnt Pathway},
journal = {Mol. Cell. Proteomics},
year = {2011},
volume = {10},
pages = {M110.002998--},
number = {1},
month = jan,
abstract = {Alternative splicing is a crucial step in the generation of protein
diversity and its misregulation is observed in many human cancer
types. By analyzing 143 colorectal samples using exon arrays, SLC39A14,
a divalent cation transporter, was identified as being aberrantly
spliced in tumor samples. SLC39A14 contains two mutually exclusive
exons 4A and 4B and the exon 4A/4B ratio was significantly altered
in adenomas (p = 3.6 x 10-10) and cancers (p = 9.4 x 10-11), independent
of microsatellite stability status. The findings were validated in
independent exon array data sets and by quantitative real-time reverse-transcription
PCR (qRT-PCR). Aberrant Wnt signaling is a hallmark of colorectal
tumorigenesis and is characterized by nuclear {beta}-catenin. Experimental
inactivation of Wnt signaling in DLD1 and Ls174T cells by knockdown
of {beta}-catenin or overexpression of dominant negative TCFs (TCF1
and TCF4) altered the 4A/4B ratio, indicating that SLC39A14 splicing
is regulated by the Wnt pathway. An altered 4A/4B ratio was also
observed in gastric and lung cancer where Wnt signaling is also known
to be aberrantly activated. The splicing factor SRSF1 and its regulator,
the kinase SRPK1, were found to be deregulated upon Wnt inactivation
in colorectal carcinoma cells. SRPK1 was also found up-regulated
in both adenoma samples (p = 1.5 x 10-5) and cancer samples (p =
5 x 10-4). In silico splicing factor binding analysis predicted SRSF1
to bind predominantly to the cancer associated exon 4B, hence, it
was hypothesized that SRPK1 activates SRSF1 through phosphorylation,
followed by SRSF1 binding to exon 4B and regulation of SLC39A14 splicing.
Indeed, siRNA-mediated knockdown of SRPK1 and SRSF1 in DLD1 and SW480
colorectal cancer cells led to a change in the 4A/4B isoform ratio,
supporting a role of these factors in the regulation of SLC39A14
splicing. In conclusion, alternative splicing of SLC39A14 was identified
in colorectal tumors and found to be regulated by the Wnt pathway,
most likely through regulation of SRPK1 and SRSF1.},
comment = {10.1074/mcp.M110.002998},
url = {http://www.mcponline.org/cgi/content/abstract/10/1/M110.002998}
}
@ARTICLE{Thorsen2011,
author = {Thorsen, Kasper and Schepeler, Troels and Oster, Bodil and Rasmussen,
Mads and Vang, Soren and Wang, Kai and Hansen, Kristian and Lamy,
Philippe and Pedersen, Jakob and Eller, Asger and Mansilla, Francisco
and Laurila, Kirsti and Wiuf, Carsten and Laurberg, Soren and Dyrskjot,
Lars and Orntoft, Torben and Andersen, Claus},
title = {Tumor-specific usage of alternative transcription start sites in
colorectal cancer identified by genome-wide exon array analysis},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {505},
number = {1},
abstract = {BACKGROUND:Approximately half of all human genes use alternative transcription
start sites (TSSs) to control mRNA levels and broaden the transcriptional
output in healthy tissues. Aberrant expression patterns promoting
carcinogenesis, however, may arise from alternative promoter usage.RESULTS:By
profiling 108 colorectal samples using exon arrays, we identified
nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5,
and SCIN) showing tumor-specific alternative TSS usage in both adenoma
and cancer samples relative to normal mucosa. Analysis of independent
exon array data sets corroborated these findings. Additionally, we
confirmed the observed patterns for selected mRNAs using quantitative
real-time reverse-transcription PCR. Interestingly, for some of the
genes, the tumor-specific TSS usage was not restricted to colorectal
cancer. A comprehensive survey of the nine genes in lung, bladder,
liver, prostate, gastric, and brain cancer revealed significantly
altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset
of these cancer types.To identify the mechanism responsible for the
shift in alternative TSS usage, we antagonized the Wnt-signaling
pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably
led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This
indicated a regulatory role of the Wnt pathway in selecting TSS,
possibly also involving TP53 and SOX9, as their transcription binding
sites were enriched in the promoters of the tumor preferred isoforms
together with their mRNA levels being increased in tumor samples.Finally,
to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry
was used to show deregulation of the total protein levels of both
TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore,
the level of nuclear TCF12 had a significant correlation to progression
free survival in a cohort of 248 stage II colorectal cancer samples.CONCLUSIONS:Alternative
TSS usage in colorectal adenoma and cancer samples has been shown
for nine genes, and OSBPL1A and TRAK1 were found to be regulated
in vitro by Wnt signaling. TCF12 protein expression was upregulated
in cancer samples and correlated with progression free survival.},
doi = {10.1186/1471-2164-12-505},
issn = {1471-2164},
pubmedid = {21999571},
url = {http://www.biomedcentral.com/1471-2164/12/505}
}
@ARTICLE{Thorsen2008,
author = {Thorsen, Kasper and Sorensen, Karina D. and Brems-Eskildsen, Anne
Sofie and Modin, Charlotte and Gaustadnes, Mette and Hein, Anne-Mette
K. and Kruhoffer, Mogens and Laurberg, Soren and Borre, Michael and
Wang, Kai and Brunak, Soren and Krainer, Adrian R. and Torring, Niels
and Dyrskjot, Lars and Andersen, Claus L. and Orntoft, Torben F.},
title = {Alternative Splicing in Colon, Bladder, and Prostate Cancer Identified
by Exon Array Analysis},
journal = {Mol. Cell. Proteomics},
year = {2008},
volume = {7},
pages = {1214--1224},
number = {7},
month = jul,
abstract = {Alternative splicing enhances proteome diversity and modulates cancer-associated
proteins. To identify tissue- and tumor-specific alternative splicing,
we used the GeneChip Human Exon 1.0 ST Array to measure whole-genome
exon expression in 102 normal and cancer tissue samples of different
stages from colon, urinary bladder, and prostate. We identified 2069
candidate alternative splicing events between normal tissue samples
from colon, bladder, and prostate and selected 15 splicing events
for RT-PCR validation, 10 of which were successfully validated by
RT-PCR and sequencing. Furthermore 23, 19, and 18 candidate tumor-specific
splicing alterations in colon, bladder, and prostate, respectively,
were selected for RT-PCR validation on an independent set of 81 normal
and tumor tissue samples. In total, seven genes with tumor-specific
splice variants were identified (ACTN1, CALD1, COL6A3, LRRFIP2, PIK4CB,
TPM1, and VCL). The validated tumor-specific splicing alterations
were highly consistent, enabling clear separation of normal and cancer
samples and in some cases even of different tumor stages. A subset
of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL)
was found in all three organs and may represent general cancer-related
splicing events. In silico protein predictions suggest that the identified
cancer-specific splice variants encode proteins with potentially
altered functions, indicating that they may be involved in pathogenesis
and hence represent novel therapeutic targets. In conclusion, we
identified and validated alternative splicing between normal tissue
samples from colon, bladder, and prostate in addition to cancer-specific
splicing events in colon, bladder, and prostate cancer that may have
diagnostic and prognostic implications.},
url = {http://www.mcponline.org/cgi/content/abstract/7/7/1214}
}
@ARTICLE{Throude2009,
author = {Throude, Mickael and Bolot, Stephanie and Bosio, Mickael and Pont,
Caroline and Sarda, Xavier and Quraishi, Umar Masood and Bourgis,
Fabienne and Lessard, Philippe and Rogowsky, Peter and Ghesquiere,
Alain and Murigneux, Alain and Charmet, Gilles and Perez, Pascual
and Salse, Jerome},
title = {Structure and expression analysis of rice paleo duplications},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {1248--1259},
number = {4},
month = mar,
abstract = {Having a well-known history of genome duplication, rice is a good
model for studying structural and functional evolution of paleo duplications.
Improved sequence alignment criteria were used to characterize 10
major chromosome-to-chromosome duplication relationships associated
with 1440 paralogous pairs, covering 47.8% of the rice genome, with
12.6% of genes that are conserved within sister blocks. Using a micro-array
experiment, a genome-wide expression map has been produced, in which
2382 genes show significant differences of expression in root, leaf
and grain. By integrating both structural (1440 paralogous pairs)
and functional information (2382 differentially expressed genes),
we identified 115 paralogous gene pairs for which at least one copy
is differentially expressed in one of the three tissues. A vast majority
of the 115 paralogous gene pairs have been neofunctionalized or subfunctionalized
as 88%, 89% and 96% of duplicates, respectively, expressed in grain,
leaf and root show distinct expression patterns. On the basis of
a Gene Ontology analysis, we have identified and characterized the
gene families that have been structurally and functionally preferentially
retained in the duplication showing that the vast majority (>85%)
of duplicated have been either lost or have been subfunctionalized
or neofunctionalized during 50-70 million years of evolution.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/4/1248}
}
@ARTICLE{Thukral2005,
author = {Thukral, Sushil K. and Nordone, Paul J. and Hu, Rong and Sullivan,
Leah and Galambos, Eric and Fitzpatrick, Vincent D. and Healy, Laura
and Bass, Michael B. and Cosenza, Mary E. and Afshari, Cynthia A.},
title = {Prediction of Nephrotoxicant Action and Identification of Candidate
Toxicity-Related Biomarkers},
journal = {Toxicol Pathol},
year = {2005},
volume = {33},
pages = {343--355},
number = {3},
month = apr,
abstract = {A vast majority of pharmacological compounds and their metabolites
are excreted via the urine, and within the complex structure of the
kidney, the proximal tubules are a main target site of nephrotoxic
compounds. We used the model nephrotoxicants mercuric chloride, 2-bromoethylamine
hydrobromide, hexachlorobutadiene, mitomycin, amphotericin, and puromycin
to elucidate time- and dose-dependent global gene expression changes
associated with proximal tubular toxicity. Male Sprague-Dawley rats
were dosed via intraperitoneal injection once daily for mercuric
chloride and amphotericin (up to 7 doses), while a single dose was
given for all other compounds. Animals were exposed to 2 different
doses of these compounds and kidney tissues were collected on day
1, 3, and 7 postdosing. Gene expression profiles were generated from
kidney RNA using 17K rat cDNA dual dye microarray and analyzed in
conjunction with histopathology. Analysis of gene expression profiles
showed that the profiles clustered based on similarities in the severity
and type of pathology of individual animals. Further, the expression
changes were indicative of tubular toxicity showing hallmarks of
tubular degeneration/regeneration and necrosis. Use of gene expression
data in predicting the type of nephrotoxicity was then tested with
a support vector machine (SVM)-based approach. A SVM prediction module
was trained using 120 profiles of total profiles divided into four
classes based on the severity of pathology and clustering. Although
mitomycin C and amphotericin B treatments did not cause toxicity,
their expression profiles were included in the SVM prediction module
to increase the sample size. Using this classifier, the SVM predicted
the type of pathology of 28 test profiles with 100% selectivity and
82% sensitivity. These data indicate that valid predictions could
be made based on gene expression changes from a small set of expression
profiles. A set of potential biomarkers showing a time- and dose-response
with respect to the progression of proximal tubular toxicity were
identified. These include several transporters (Slc21a2, Slc15, Slc34a2),
Kim 1, IGFbp-1, osteopontin, {alpha}-fibrinogen, and Gst{alpha}.},
url = {http://tpx.sagepub.com/cgi/content/abstract/33/3/343}
}
@ARTICLE{Thulin2008,
author = {Thulin, Petra and Rafter, Ingalill and Stockling, Kenneth and Tomkiewicz,
Celine and Norjavaara, Ensio and Aggerbeck, Martine and Hellmold,
Heike and Ehrenborg, Ewa and Andersson, Ulf and Cotgreave, Ian and
Glinghammar, Björn},
title = {PPAR[alpha] regulates the hepatotoxic biomarker alanine aminotransferase
(ALT1) gene expression in human hepatocytes},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {231},
pages = {1--9},
number = {1},
month = aug,
abstract = {In this work, we investigated a potential mechanism behind the observation
of increased aminotransferase levels in a phase I clinical trial
using a lipid-lowering drug, the peroxisome proliferator-activated
receptor (PPAR) [alpha] agonist, AZD4619. In healthy volunteers treated
with AZD4619, serum alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) activities were elevated without an increase
in other markers for liver injury. These increases in serum aminotransferases
have previously been reported in some patients receiving another
PPAR[alpha] agonist, fenofibrate. In subsequent in vitro studies,
we observed increased expression of ALT1 protein and mRNA in human
hepatocytes after treatment with fenofibric acid. The PPAR effect
on ALT1 expression was shown to act through a direct transcriptional
mechanism involving at least one PPAR response element (PPRE) in
the proximal ALT1 promoter, while no effect of fenofibrate and AZD4619
was observed on the ALT2 promoter. Binding of PPARs to the PPRE located
at - 574 bp from the transcriptional start site was confirmed on
both synthetic oligonucleotides and DNA in hepatocytes. These data
show that intracellular ALT expression is regulated by PPAR agonists
and that this mechanism might contribute to increased ALT activity
in serum.},
issn = {0041-008X},
keywords = {Alanine aminotransferase, Hepatotoxicity, Liver injury, ALT, AST,
Clinical trial, GPT1, GPT2, Regulation, Serum, PPAR},
url = {http://www.sciencedirect.com/science/article/B6WXH-4S4TNTJ-1/2/f48ee32a0ca4cfe6a7e59861c5933bd4}
}
@ARTICLE{Thum2008,
author = {Thum, Thomas and Borlak, Jurgen},
title = {LOX-1 Receptor Blockade Abrogates oxLDL-induced Oxidative DNA Damage
and Prevents Activation of the Transcriptional Repressor Oct-1 in
Human Coronary Arterial Endothelium},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {19456--19464},
number = {28},
month = jul,
abstract = {Activation of the lectin-like oxLDL receptor (LOX-1) promotes atherosclerosis.
Oxidized LDL (oxLDL) increases production of reactive oxygen species
(ROS) and leads to the development of endothelial dysfunction. The
molecular causes for oxLDL to induce oxidative DNA damage and metabolic
dysfunction remain uncertain. Here we report treatment of cultured
human coronary arterial endothelial cells (HCAEC) with oxLDL to cause
oxidative DNA damage as determined by a 3-fold increase in 8-OH-desoxyguanosine
adduct formation and a 4-fold induction of the growth arrest and
DNA damage-inducible transcripts GADD45 and GADD153. Oxidative stress
resulted in activation of Oct-1, a transcriptional repressor of various
vascular cytochrome P450 (CYP) monooxygenases. Activation of Oct-1
was protein kinase C (PKC)-mediated. Binding of Oct-1 to promoter
sequences of CYP monooxygenases was increased upon treatment of HCAEC
with oxLDL. This resulted in repressed production of endothelium-derived
hyperpolarization factor 11,12-epoxyeicosatrieonic acid. Small interference
RNA-mediated functional knockdown of Oct-1 prevented oxLDL-mediated
silencing of CYP expression. Inhibition of LOX-1 attenuated oxLDL-mediated
endothelial DNA damage, Oct-1/DNA binding, and reversed impaired
production of EDHF. Taken collectively, oxLDL induced oxidative DNA
damage and activation of Oct-1 to result in metabolic dysfunction
of coronary arterial endothelium.},
url = {http://www.jbc.org/cgi/content/abstract/283/28/19456}
}
@ARTICLE{Thum2004,
author = {Thum, Thomas and Borlak, Jurgen},
title = {Mechanistic Role of Cytochrome P450 Monooxygenases in Oxidized Low-Density
Lipoprotein-Induced Vascular Injury: Therapy Through LOX-1 Receptor
Antagonism?},
journal = {Circ. Res.},
year = {2004},
volume = {94},
pages = {e1--13},
number = {1},
month = jan,
abstract = {Oxidized low-density lipoprotein (oxLDL) is an important risk factor
for vascular injury. Its role on coronary vasoconstriction remains
speculative. Endothelial monooxygenases (cytochrome P450s [CYPs])
are regulators of vascular tonus through production of epoxy fatty
acids. We investigated the effects of oxLDL on CYP monooxygenases
in human arterial coronary endothelial cells and explanted healthy
and atherosclerotic aortae. We found oxLDL to induce radical oxygen
species production via the action of NADPH oxidase NOX4. Intracellular
radical oxygen species production prompted reduced protein expression
of the transcriptional regulator nuclear factor 1 (NF-1). We identified
novel DNA binding sites for NF-1 in promoter regions of CYPs. DNA
binding of NF-1 was confirmed by electromobility shift assays. OxLDL
repressed DNA binding of NF-1 and diminished transcript level of
CYP genes targeted by this factor. The production of endothelial-derived
hyperpolarization factor, a key regulator of vascular tonus, was
also reduced. Repression of CYP monooxygenases was reversed, and
production of endothelial-derived hyperpolarization factor was normalized
after treatment of endothelium with the lectin-like oxLDL receptor
antagonist {kappa}-carrageenan or blocking of LOX-1 with a specific
antibody. This suggests a mechanistic role of CYP monooxygenases
in oxLDL-induced vascular injury. Therapy of endothelial dysfunction
through LOX-1 receptor antagonism will be an interesting avenue to
explore. The full text of this article is available online at http://www.circresaha.org.},
url = {http://circres.ahajournals.org/cgi/content/abstract/94/1/e1}
}
@ARTICLE{Thum2007,
author = {Thum, Thomas and Galuppo, Paolo and Wolf, Christian and Fiedler,
Jan and Kneitz, Susanne and van Laake, Linda W. and Doevendans, Pieter
A. and Mummery, Christine L. and Borlak, Jurgen and Haverich, Axel
and Gross, Carina and Engelhardt, Stefan and Ertl, Georg and Bauersachs,
Johann},
title = {MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming
in Heart Failure},
journal = {Circulation},
year = {2007},
volume = {116},
pages = {258--267},
number = {3},
month = jul,
abstract = {Background-- Chronic heart failure is characterized by left ventricular
remodeling and reactivation of a fetal gene program; the underlying
mechanisms are only partly understood. Here we provide evidence that
cardiac microRNAs, recently discovered key regulators of gene expression,
contribute to the transcriptional changes observed in heart failure.
Methods and Results-- Cardiac transcriptome analyses revealed striking
similarities between fetal and failing human heart tissue. Using
microRNA arrays, we discovered profound alterations of microRNA expression
in failing hearts. These changes closely mimicked the microRNA expression
pattern observed in fetal cardiac tissue. Bioinformatic analysis
demonstrated a striking concordance between regulated messenger RNA
expression in heart failure and the presence of microRNA binding
sites in the respective 3' untranslated regions. Messenger RNAs upregulated
in the failing heart contained preferentially binding sites for downregulated
microRNAs and vice versa. Mechanistically, transfection of cardiomyocytes
with a set of fetal microRNAs induced cellular hypertrophy as well
as changes in gene expression comparable to the failing heart. Conclusions--
Our data support a novel mode of regulation for the transcriptional
changes in cardiac failure. Reactivation of a fetal microRNA program
substantially contributes to alterations of gene expression in the
failing human heart.},
url = {http://circ.ahajournals.org/cgi/content/abstract/116/3/258}
}
@ARTICLE{Thum2003,
author = {Thum, Thomas and Tsikas, Dimitris and Frölich, Jürgen C and Borlak,
Jürgen},
title = {Growth hormone induces eNOS expression and nitric oxide release in
a cultured human endothelial cell line},
journal = {FEBS Letters},
year = {2003},
volume = {555},
pages = {567--571},
number = {3},
month = dec,
abstract = {Growth hormone deficiency is linked to cardiovascular disease and
particularly increased peripheral vascular resistance. Surprisingly,
its role in endothelial nitric oxide (NO) synthetase (eNOS) regulation
and NO release is basically unknown. We therefore studied the effects
of different doses of somatotropin in cultures of a human endothelial
cell line (EAhy926). We investigated expression and activity of eNOS,
as well as other target genes known to be deregulated in cardiovascular
disease including E-selectin and the lectin-like oxidized low density
lipoprotein receptor. Treatment of cultured human endothelial cells
with somatotropin resulted in significant (P<0.05) increases of eNOS
gene and protein expression, as well as NO release, whereas production
of intracellular reactive oxygen species was significantly reduced,
at the highest somatotropin dose level. The enhanced eNOS gene/protein
expression and enzyme activity correlate well. Our findings are suggestive
for a novel role of growth hormone in endothelial biology, and particularly
NO production.},
issn = {0014-5793},
keywords = {Growth hormone, Somatotropin, Endothelial nitric oxide synthetase,
Nitric oxide, Growth hormone deficiency, Reactive oxygen species,
Endothelial cell},
url = {http://www.sciencedirect.com/science/article/B6T36-4B3MMPW-5/2/619bb2b84c2d5efb5c009eb53bc9a3fd}
}
@ARTICLE{Thurman2007,
author = {Thurman, Joshua M. and Lenderink, Amanda M. and Royer, Pamela A.
and Coleman, Kathrin E. and Zhou, Jian and Lambris, John D. and Nemenoff,
Raphael A. and Quigg, Richard J. and Holers, V. Michael},
title = {C3a Is Required for the Production of CXC Chemokines by Tubular Epithelial
Cells after Renal Ishemia/Reperfusion},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {1819--1828},
number = {3},
month = feb,
abstract = {The complement system is one of the major ways by which the body detects
injury to self cells, and the alternative pathway of complement is
rapidly activated within the tubulointerstitium after renal ischemia/reperfusion
(I/R). In the current study, we investigate the hypothesis that recognition
of tubular injury by the complement system is a major mechanism by
which the systemic inflammatory response is initiated. Gene array
analysis of mouse kidney following I/R initially identified MIP-2
(CXCL2) and keratinocyte-derived chemokine (KC or CXCL1) as factors
that are produced in a complement-dependent fashion. Using in situ
hybridization, we next demonstrated that these factors are expressed
in tubular epithelial cells of postischemic kidneys. Mouse proximal
tubular epithelial cells (PTECs) in culture were then exposed to
an intact alternative pathway and were found to rapidly produce both
chemokines. Selective antagonism of the C3a receptor significantly
attenuated production of MIP-2 and KC by PTECs, whereas C5a receptor
antagonism and prevention of membrane attack complex (MAC) formation
did not have a significant effect. Treatment of PTECs with an NF-{kappa}B
inhibitor also prevented full expression of these factors in response
to an intact alternative pathway. In summary, alternative pathway
activation after renal I/R induces production of MIP-2 and KC by
PTECs. This innate immune system thereby recognizes hypoxic injury
and triggers a systemic inflammatory response through the generation
of C3a and subsequent activation of the NF-{kappa}B system.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/3/1819}
}
@ARTICLE{Thurmond2008,
author = {Thurmond, John and Butchbach, Matthew E. R. and Palomo, Marty and
Pease, Brian and Rao, Munagala and Bedell, Louis and Keyvan, Monica
and Pai, Grace and Mishra, Rama and Haraldsson, Magnus and Andresson,
Thorkell and Bragason, Gisli and Thosteinsdottir, Margret and Bjornsson,
Jon Mar and Coovert, Daniel D. and Burghes, Arthur H. M. and Gurney,
Mark E. and Singh, Jasbir},
title = {Synthesis and Biological Evaluation of Novel 2,4-Diaminoquinazoline
Derivatives as SMN2 Promoter Activators for the Potential Treatment
of Spinal Muscular Atrophy},
journal = {Journal of Medicinal Chemistry},
year = {2008},
volume = {51},
pages = {449-469},
number = {3},
note = {PMID: 18205293},
doi = {10.1021/jm061475p},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jm061475p},
url = {http://pubs.acs.org/doi/abs/10.1021/jm061475p}
}
@ARTICLE{Theron2009,
author = {Théron, Laetitia and Chevarin, Laetitia and Robert, Nathalie and
Dutertre, Christophe and Santé-Lhoutellier, Véronique},
title = {Time course of peptide fingerprints in semimembranosus and biceps
femoris muscles during Bayonne ham processing},
journal = {Meat Science},
year = {2009},
volume = {82},
pages = {272--277},
number = {2},
month = jun,
abstract = {The aim of this work was to define reliable markers of muscle and
processing time in dry-cured ham using a rapid, precise semi quantitative
method for the protein fraction soluble in low ionic strength buffer.
For this purpose protein labchip Agilent was used to separate proteins
and peptides and accurately determine their molecular weights and
concentrations electrophoretically. In this way the protein fingerprinting
of dry-cured ham at different process times was characterised, together
with targets and products of proteolysis. In addition, the comparison
of all the electrophoregrams indicated muscle and dry-curing process
markers.},
issn = {0309-1740},
keywords = {Dry-cured ham, Bayonne ham, Proteolysis, Protein fingerprinting, semimembranosus,
biceps femoris},
url = {http://www.sciencedirect.com/science/article/B6T9G-4VFK82K-3/2/21a61cc9e5d08c8bc685e952690ed64e}
}
@ARTICLE{Tiago2011,
author = {Tiago, Daniel and Laize, Vincent and Bargelloni, Luca and Ferraresso,
Serena and Romualdi, Chiara and Cancela, M},
title = {Global analysis of gene expression in mineralizing fish vertebra-derived
cell lines: new insights into anti-mineralogenic effect of vanadate},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {310},
number = {1},
abstract = {BACKGROUND:Fish has been deemed suitable to study the complex mechanisms
of vertebrate skeletogenesis and gilthead seabream (Sparus aurata),
a marine teleost with acellular bone, has been successfully used
in recent years to study the function and regulation of bone and
cartilage related genes during development and in adult animals.
Tools recently developed for gilthead seabream, e.g. mineralogenic
cell lines and a 4 x 44K Agilent oligo-array, were used to identify
molecular determinants of in vitro mineralization and genes involved
in anti-mineralogenic action of vanadate.RESULTS:Global analysis
of gene expression identified 4,223 and 4,147 genes differentially
expressed (fold change - FC > 1.5) during in vitro mineralization
of VSa13 (pre-chondrocyte) and VSa16 (pre-osteoblast) cells, respectively.
Comparative analysis indicated that nearly 45% of these genes are
common to both cell lines and gene ontology (GO) classification is
also similar for both cell types. Up-regulated genes (FC > 10) were
mainly associated with transport, matrix/membrane, metabolism and
signaling, while down-regulated genes were mainly associated with
metabolism, calcium binding, transport and signaling. Analysis of
gene expression in proliferative and mineralizing cells exposed to
vanadate revealed 1,779 and 1,136 differentially expressed genes,
respectively. Of these genes, 67 exhibited reverse patterns of expression
upon vanadate treatment during proliferation or mineralization.CONCLUSIONS:Comparative
analysis of expression data from fish and data available in the literature
for mammalian cell systems (bone-derived cells undergoing differentiation)
indicate that the same type of genes, and in some cases the same
orthologs, are involved in mechanisms of in vitro mineralization,
suggesting their conservation throughout vertebrate evolution and
across cell types. Array technology also allowed identification of
genes differentially expressed upon exposure of fish cell lines to
vanadate and likely involved in its anti-mineralogenic activity.
Many were found to be unknown or they were never associated to bone
homeostasis previously, thus providing a set of potential candidates
whose study will likely bring insights into the complex mechanisms
of tissue mineralization and bone formation.},
doi = {10.1186/1471-2164-12-310},
issn = {1471-2164},
pubmedid = {21668972},
url = {http://www.biomedcentral.com/1471-2164/12/310}
}
@ARTICLE{Tian2011,
author = {Fei Tian and Juan Luo and Huanmin Zhang and Jiuzhou Song},
title = {MiRNA expression signatures induced by Marek's disease virus infection
in chickens},
journal = {Genomics},
year = {2011},
pages = { - },
number = {0},
abstract = {MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression
at the post-transcriptional level. Emerging evidence suggests that
differential miRNA expression is associated with viral infection
and cancer. Marek's disease virus infection induces lymphoma in chickens.
However, the host defense response against Marek's disease (MD) progression
remains poorly understood. Here, we utilized microarrays to screen
miRNAs that were sensitive to Marek's disease virus (MDV) infection.
QRT-PCR analysis confirmed the microarray data and revealed expression
patterns of some miRNAs in tumor samples. Chicken miRNA gga-miR-15b,
which is reduced in infected susceptible chickens and splenic tumors,
controls the expression of ATF2 (activating transcription factor
2). ATF2 is significantly increased in the same group. Our results
indicated that differential expression of miRNA in resistant and
susceptible chickens was caused by MDV infection, which effectively
influenced protein expression of ATF2. This latter result might be
related to Marek's disease resistance/susceptibility.},
doi = {10.1016/j.ygeno.2011.11.004},
issn = {0888-7543},
keywords = {MicroRNA},
url = {http://www.sciencedirect.com/science/article/pii/S0888754311002618}
}
@ARTICLE{Tian2011d,
author = {Tian, Jing and Fratz, Sohrab and Hou, Yali and Lu, Qing and Gorlach,
Agnes and Hess, John and Schreiber, Christian and Datar, Sanjeev
A. and Oishi, Peter and Nechtman, John and Podolsky, Robert and She,
Jin-Xiong and Fineman, Jeffrey R. and Black, Stephen M.},
title = {Delineating the angiogenic gene expression profile before pulmonary
vascular remodeling in a lamb model of congenital heart disease},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {87--98},
number = {2},
month = jan,
abstract = {Disordered angiogenesis is implicated in pulmonary vascular remodeling
secondary to congenital heart diseases (CHD). However, the underlying
genes are not well delineated. We showed previously that an ovine
model of CHD with increased pulmonary blood flow (PBF, Shunt) has
an "angiogenesis burst" between 1 and 4 wk of age. Thus we hypothesized
that the increased PBF elicited a proangiogenic gene expression profile
before onset of vessel growth. To test this we utilized microarray
analysis to identify genes that could be responsible for the angiogenic
response. Total RNA was isolated from lungs of Shunt and control
lambs at 3 days of age and hybridized to Affymetrix gene chips for
microarray analyses (n = 8/group). Eighty-nine angiogenesis-related
genes were found to be upregulated and 26 angiogenesis-related genes
downregulated in Shunt compared with control lungs (cutting at 1.2-fold
difference, P < 0.05). We then confirmed upregulation of proangiogenic
genes FGF2, Angiopoietin2 (Angpt2), and Birc5 at mRNA and protein
levels and upregulation of ccl2 at mRNA level in 3-day Shunt lungs.
Furthermore, we found that pulmonary arterial endothelial cells (PAEC)
isolated from fetal lambs exhibited increased expression of FGF2,
Angpt2, Birc5, and ccl2 and enhanced angiogenesis when exposed to
elevated shear stress (35 dyn/cm2) compared with cells exposed to
more physiological shear stress (20 dyn/cm2). Finally, we demonstrated
that blocking FGF2, Angpt2, Birc5, or ccl2 signaling with neutralizing
antibodies or small interfering RNA (siRNA) significantly decreased
the angiogenic response induced by shear stress. In conclusion, we
have identified a "proangiogenic" gene expression profile in a lamb
model of CHD with increased PBF that precedes onset of pulmonary
vascular remodeling. Our data indicate that FGF2, Angpt2, Birc5,
and ccl2 may play important roles in the angiogenic response.},
comment = {10.1152/physiolgenomics.00135.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/2/87}
}
@ARTICLE{Tian2005,
author = {Tian, Jane and Ishibashi, Kazuki and Ishibashi, Kazuko and Reiser,
Karen and Grebe, Rhonda and Biswal, Shyam and Gehlbach, Peter and
Handa, James T.},
title = {Advanced glycation endproduct-induced aging of the retinal pigment
epithelium and choroid: A comprehensive transcriptional response},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {11846--11851},
number = {33},
month = aug,
abstract = {Advanced glycation endproduct (AGE) formation is a trigger for the
onset of age-related disease. To evaluate AGE-induced change in the
ocular fundus, 5-mo-old C57BL/6 mice were given low-dose D-galactose
(D-gal) for 8 wk and evaluated by AGE fluorescence, electroretinography
(ERG), electron microscopy, and microarray analysis for 20 wk. Although
AGE fluorescence was increased in D-gal-treated retinal pigment epithelium
(RPE)-choroid compared with controls at all time points, ERG showed
no AGE-induced functional toxicity. Progressive ultrastructural aging
in the RPE-choroid was associated temporally with a transcriptional
response of early inflammation, matrix expansion, and aberrant lipid
processing and, later, down-regulation of energy metabolism genes,
up-regulation of crystallin genes, and altered expression of cell
structure genes. The overall transcriptome is similar to the generalized
aging response of unrelated cell types. A subset of transcriptional
changes is similar to early atherosclerosis, a chronic inflammatory
disease characterized by matrix expansion and lipid deposition. These
changes suggest an important contribution of a single environmental
stimulus to the complex aging response.},
url = {http://www.pnas.org/cgi/content/abstract/102/33/11846}
}
@ARTICLE{Tian2009,
author = {Tian, Jing and Smith, Anita and Nechtman, John and Podolsky, Robert
and Aggarwal, Saurabh and Snead, Connie and Kumar, Sanjiv and Elgaish,
Manal and Oishi, Peter and Goerlach, Agnes and Fratz, Sohrab and
Hess, John and Catravas, John D. and Verin, Alexander. D. and Fineman,
Jeffrey R. and She, Jin-Xiong and Black, Stephen M.},
title = {Effect of PPAR{gamma} inhibition on pulmonary endothelial cell gene
expression: gene profiling in pulmonary hypertension},
journal = {Physiol Genomics},
year = {2009},
volume = {40},
pages = {48--60},
number = {1},
month = dec,
abstract = {Peroxisome proliferator-activated receptor type gamma (PPAR{gamma})
is a subgroup of the PPAR transcription factor family. Recent studies
indicate that loss of PPAR{gamma} is associated with the development
of pulmonary hypertension (PH). We hypothesized that the endothelial
dysfunction associated with PPAR{gamma} inhibition may play an important
role in the disease process by altering cellular gene expression
and signaling cascades. We utilized microarray analysis to determine
if PPAR{gamma} inhibition induced changes in gene expression in pulmonary
arterial endothelial cells (PAEC). We identified 100 genes and expressed
sequence tags (ESTs) that were upregulated by >1.5-fold and 21 genes
and ESTs that were downregulated by >1.3-fold (P < 0.05) by PPAR{gamma}
inhibition. The upregulated genes can be broadly classified into
four functional groups: cell cycle, angiogenesis, ubiquitin system,
and zinc finger proteins. The genes with the highest fold change
in expression: hyaluronan-mediated motility receptor (HMMR), VEGF
receptor 2 (Flk-1), endothelial PAS domain protein 1 (EPAS1), basic
fibroblast growth factor (FGF-2), and caveolin-1 in PAEC were validated
by real time RT-PCR. We further validated the upregulation of HMMR,
Flk-1, FGF2, and caveolin-1 by Western blot analysis. In keeping
with the microarray results, PPAR{gamma} inhibition led to re-entry
of cell cycle at G1/S phase and cyclin C upregulation. PPAR{gamma}
inhibition also exacerbated VEGF-induced endothelial barrier disruption.
Finally we confirmed the downregulation of PPAR{gamma} and the upregulation
of HMMR, Flk-1, FGF2, and Cav-1 proteins in the peripheral lung tissues
of an ovine model of PH. In conclusion, we have identified an array
of endothelial genes modulated by attenuated PPAR{gamma} signaling
that may play important roles in the development of PH.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/40/1/48}
}
@ARTICLE{Tian2010,
author = {Tian, Xiaolin and Jin, Ramon U. and Bredemeyer, Andrew J. and Oates,
Edward J. and Blazewska, Katarzyna M. and McKenna, Charles E. and
Mills, Jason C.},
title = {RAB26 and RAB3D Are Direct Transcriptional Targets of MIST1 That
Regulate Exocrine Granule Maturation},
journal = {Mol. Cell. Biol.},
year = {2010},
volume = {30},
pages = {1269--1284},
number = {5},
month = mar,
abstract = {Little is known about how differentiating cells reorganize their cellular
structure to perform specialized physiological functions. MIST1,
an evolutionarily conserved transcription factor, is required for
the formation of large, specialized secretory vesicles in gastric
zymogenic (chief) cells (ZCs) as they differentiate from their mucous
neck cell progenitors. Here, we show that MIST1 binds to highly conserved
CATATG E-boxes to directly activate transcription of 6 genes, including
those encoding the small GTPases RAB26 and RAB3D. We next show that
RAB26 and RAB3D expression is significantly downregulated in Mist1-/-
ZCs, suggesting that MIST1 establishes large secretory granules by
inducing RAB transcription. To test this hypothesis, we transfected
human gastric cancer cell lines stably expressing MIST1 with red
fluorescent protein (RFP)-tagged pepsinogen C, a key secretory product
of ZCs. Those cells upregulate expression of RAB26 and RAB3D to form
large secretory granules, whereas control, non-MIST1-expressing cells
do not. Moreover, granule formation in MIST1-expressing cells requires
RAB activity because treatment with a RAB prenylation inhibitor and
transfection of dominant negative RAB26 abrogate granule formation.
Together, our data establish the molecular process by which a transcription
factor can directly induce fundamental cellular architecture changes
by increasing transcription of specific cellular effectors that act
to organize a unique subcellular compartment.},
url = {http://mcb.asm.org/cgi/content/abstract/30/5/1269}
}
@ARTICLE{Tian2011c,
author = {Tian, Yingfang and Apperson, Michelle L. and Ander, Bradley P. and
Liu, Dazhi and Stomova, Boryana S. and Jickling, Glen C. and Enriquez,
Richelle and Agius, Mark A. and Sharp, Frank R.},
title = {Differences in exon expression and alternatively spliced genes in
blood of multiple sclerosis compared to healthy control subjects},
journal = {Journal of Neuroimmunology},
year = {2011},
volume = {230},
pages = {124--129},
number = {1-2},
month = jan,
abstract = {Using whole genome exon microarrays 120 exons were differentially
expressed between medication-free multiple sclerosis (MS) subjects
in remission and healthy control subjects (HS) (p < 0.001, fold change > 1.2).
These exons differentiated MS from HS using cluster analyses, principal
components analyses (PCAs) and cross-validation. In addition, 340
genes (transcripts) were predicted to be alternatively spliced in
MS compared to HS. These findings may provide insight into the pathophysiology
of MS and potentially provide prognostic and diagnostic biomarkers.
However, given that multiple comparisons were performed on a very
small sample, these preliminary findings require confirmation using
a much larger independent cohort.},
issn = {0165-5728},
keywords = {Multiple sclerosis, Gene expression profiling, Exon expression profiles,
Alternative splicing, Blood biomarker},
url = {http://www.sciencedirect.com/science/article/pii/S0165572810004091}
}
@ARTICLE{Tian2011a,
author = {Tian, Yingfang and Gunther, Joan R. and Liao, Isaac H. and Liu, Dazhi
and Ander, Bradley P. and Stamova, Boryana S. and Lit, Lisa and Jickling,
Glen C. and Xu, Huichun and Zhan, Xinhua and Sharp, Frank R.},
title = {GABA- and acetylcholine-related gene expression in blood correlate
with tic severity and microarray evidence for alternative splicing
in Tourette syndrome: A pilot study},
journal = {Brain Research},
year = {2011},
volume = {1381},
pages = {228--236},
month = mar,
abstract = {Tourette syndrome (TS) is a complex childhood neurodevelopmental disorder
characterized by motor and vocal tics. Recently, altered numbers
of GABAergic-parvalbumin (PV) and cholinergic interneurons were observed
in the basal ganglia of individuals with TS. Thus, we postulated
that gamma-amino butyric acid (GABA)- and acetylcholine (ACh)-related
genes might be associated with the pathophysiology of TS. Total RNA
isolated from whole blood of 26 un-medicated TS subjects and 23 healthy
controls (HC) was processed on Affymetrix Human Exon 1.0 ST arrays.
Data were analyzed to identify genes whose expression correlated
with tic severity in TS, and to identify genes differentially spliced
in TS compared to HC subjects. Many genes (3627) correlated with
tic severity in TS (p < 0.05) among which GABA- (p = 2.1 × 10-3)
and ACh- (p = 4.25 × 10-8) related genes were significantly over-represented.
Moreover, several GABA and ACh-related genes were predicted to be
alternatively spliced in TS compared to HC including GABA receptors
GABRA4 and GABRG1, the nicotinic ACh receptor CHRNA4 and cholinergic
differentiation factor (CDF). This pilot study suggests that at least
some of these GABA- and ACh-related genes observed in blood that
correlate with tics or are alternatively spliced are involved in
the pathophysiology of TS and tics.},
issn = {0006-8993},
keywords = {Gene expression profiling, Tourette syndrome, Blood, GABA, Acetylcholine,
Alternative splicing},
url = {http://www.sciencedirect.com/science/article/pii/S000689931100062X}
}
@ARTICLE{Tian2011b,
author = {Tian, Yingfang and Liao, Isaac H. and Zhan, Xinhua and Gunther, Joan
R. and Ander, Bradley P. and Liu, Dazhi and Lit, Lisa and Jickling,
Glen C. and Corbett, Blythe A. and Bos-Veneman, Netty G.P. and Hoekstra,
Pieter J. and Sharp, Frank R.},
title = {Exon expression and alternatively spliced genes in tourette syndrome},
journal = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics},
year = {2011},
volume = {156},
pages = {72--78},
number = {1},
abstract = {Abstract Tourette Syndrome (TS) is diagnosed based upon clinical criteria
including motor and vocal tics. We hypothesized that differences
in exon expression and splicing might be useful for pathophysiology
and diagnosis. To demonstrate exon expression and alternatively spliced
gene differences in blood of individuals with TS compared to healthy
controls (HC), RNA was isolated from the blood of 26 un-medicated
TS subjects and 23 HC. Each sample was run on Affymetrix Human Exon
1.0 ST (HuExon) arrays and on 3′ biased U133 Plus 2.0 (HuU133)
arrays. To investigate the differentially expressed exons and transcripts,
analyses of covariance (ANCOVA) were performed, controlling for age,
gender, and batch. Differential alternative splicing patterns between
TS and HC were identified using analyses of variance (ANOVA) models
in Partek. Three hundred and seventy-six exon probe sets were differentially
expressed between TS and HC (raw P < 0.005, fold change >|1.2|)
that separated TS and HC subjects using hierarchical clustering and
Principal Components Analysis. The probe sets predicted TS compared
to HC with a >90% sensitivity and specificity using a 10-fold cross-validation.
Ninety genes (transcripts) had differential expression of a single
exon (raw P < 0.005) and were predicted to be alternatively spliced
(raw P < 0.05) in TS compared to HC. These preliminary findings
might provide insight into the pathophysiology of TS and potentially
provide prognostic and diagnostic biomarkers. However, the findings
are tempered by the small sample size and multiple comparisons and
require confirmation using PCR or deep RNA sequencing and a much
larger patient population. © 2010 Wiley-Liss, Inc.},
doi = {10.1002/ajmg.b.31140},
issn = {1552-485X},
keywords = {Tourette Syndrome, gene expression profiling, exon expression profiles,
alternative splicing, blood biomarker},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.31140}
}
@ARTICLE{Tiede2009,
author = {Tiede, Stephan and Koop, Norbert and Kloepper, Jennifer E. and Fässler,
Reinhard and Paus, Ralf},
title = {Nonviral In Situ Green Fluorescent Protein Labeling and Culture of
Primary, Adult Human Hair Follicle Epithelial Progenitor Cells},
journal = {STEM CELLS},
year = {2009},
volume = {27},
pages = {2793--2803},
number = {11},
abstract = {Abstract 10.1002/stem.213.abs In this article we show that cloning
of the human K15 promoter before a green fluorescence protein (GFP)/geneticin-resistance
cassette and transfection of microdissected, organ-cultured adult
human scalp hair follicles generates specific K15 promoter–driven
GFP expression in their stem cell–rich bulge region. K15-GFP+ cells
can be visualized in situ by GFP fluorescence and 2-photon laser
scanning microscopy. Vital K15-GFP+ progenitor cells can then be
selected by using the criteria of their green fluorescence, adhesion
to collagen type IV and fibronectin, and geneticin resistance. Propagated
K15-GFP+ cells express epithelial progenitor markers, show the expected
differential gene expression profile of human bulge epithelium, and
form holoclones. This application of nonretroviral, K15 promoter–driven,
GFP labeling to adult human hair follicles facilitates the characterization
and manipulation of human epithelial stem cells, both in situ and
in vitro, and should be transferable to other complex human tissues.
STEM CELLS 2009;27:2793–2803},
issn = {1549-4918},
keywords = {Adult stem cells, Clonal assays, Differentiation, Gene targeting,
Green fluorescent protein, In vivo optical imaging, Progenitor cells,
Tissue-specific stem cells},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/stem.213}
}
@ARTICLE{Tienen2010,
author = {van Tienen, Florence H. and Lindsey, Patrick J. and van der Kallen,
Carla J. and Smeets, Hubert J.},
title = {Prolonged Nrf1 overexpression triggers adipocyte inflammation and
insulin resistance},
journal = {Journal of Cellular Biochemistry},
year = {2010},
volume = {111},
pages = {1575--1585},
number = {6},
abstract = {Abstract Adipose tissue is currently being recognized as an important
endocrine organ, carrying defects in a number of metabolic diseases.
Mitochondria play a key role in normal adipose tissue function and
mitochondrial alterations can result in pathology, like lipodystrophy
or type 2 diabetes. Although Pgc1α is regarded as the main regulator
of mitochondrial function, downstream Nrf1 is the key regulator of
mitochondrial biogenesis. Nrf1 is also involved in a wide range of
other processes, including proliferation, innate immune response,
and apoptosis. To determine transcriptional targets of Nrf1, 3T3-L1
preadipocytes were transfected with either pNrf1 or a control vector.
Two days post-confluence, 3T3-L1 preadipocytes were allowed to differentiate.
At day 8 of differentiation, Nrf1 overexpressing cells had an increased
mtDNA copy number and reduced lipid content. This was not associated
with an increased ATP production rate per cell. Using global gene
expression analysis, we observed that Nrf1 overexpression stimulated
cell proliferation, apoptosis, and cytokine expression. In addition,
prolonged Nrf1 induced an adipokine expression profile of insulin
resistant adipocytes. Nrf1 has a wide range of transcriptional targets,
stimulators as well as inhibitors of adipose tissue functioning.
Therefore, post-transcriptional regulation of Nrf1, or stimulating
specific Nrf1 targets may be a more suitable approach for stimulating
mitochondrial biogenesis and treating adipose tissue defects, instead
of directly stimulating Nrf1 expression. In addition, our results
show that short-term effects can drastically differ from long-term
effects. J. Cell. Biochem. 111: 1575–1585, 2010. © 2010 Wiley-Liss,
Inc.},
doi = {10.1002/jcb.22889},
issn = {1097-4644},
keywords = {adipocytes, gene expression, mitochondria, Nrf1},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.22889}
}
@ARTICLE{Tienen2011,
author = {van Tienen, F H J and van der Kallen, C J H and Lindsey, P J and
Wanders, R J and van Greevenbroek, M M and Smeets, H J M},
title = {Preadipocytes of type 2 diabetes subjects display an intrinsic gene
expression profile of decreased differentiation capacity},
journal = {Int J Obes},
year = {2011},
pages = {--},
month = feb,
issn = {1476-5497},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/ijo.2010.275}
}
@ARTICLE{Tijet2006,
author = {Tijet, Nathalie and Boutros, Paul C. and Moffat, Ivy D. and Okey,
Allan B. and Tuomisto, Jouko and Pohjanvirta, Raimo},
title = {Aryl Hydrocarbon Receptor Regulates Distinct Dioxin-Dependent and
Dioxin-Independent Gene Batteries},
journal = {Mol. Pharmacol.},
year = {2006},
volume = {69},
pages = {140--153},
number = {1},
month = jan,
abstract = {Conventional biochemical and molecular techniques identified previously
several genes whose expression is regulated by the aryl hydrocarbon
receptor (AHR). We sought to map the complete spectrum of AHR-dependent
genes in male adult liver using expression arrays to contrast mRNA
profiles in Ahr-null mice (Ahr-/-) with those in mice with wild-type
AHR (Ahr+/+). Transcript profiles were determined both in untreated
mice and in mice treated 19 h earlier with 1000 {micro}g/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD). Expression of 456 ProbeSets was significantly altered by
TCDD in an AHR-dependent manner, including members of the classic
AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In
the absence of exogenous ligand, AHR status alone affected expression
of 392 ProbeSets, suggesting that the AHR has multiple functions
in normal physiology. In Ahr-/- mice, only 32 ProbeSets exhibited
responses to TCDD, indicating that the AHR is required for virtually
all transcriptional responses to dioxin exposure in liver. The flavin-containing
monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible,
were highly induced by TCDD in an AHR-dependent manner. The estrogen
receptor {alpha} as well as two estrogen-receptor-related genes ({alpha}
and {gamma}) exhibit AHR-dependent expression, thereby extending
cross-talk opportunities between the intensively studied AHR and
estrogen receptor pathways. p53 binding sites are over-represented
in genes down-regulated by TCDD, suggesting that TCDD inhibits p53
transcriptional activity. Overall, our study identifies a wide range
of genes that depend on the AHR, either for constitutive expression
or for response to TCDD.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/69/1/140}
}
@ARTICLE{Tiller2012,
author = {Tiller, Nadine and Weingartner, Magdalena and Thiele, Wolfram and
Maximova, Eugenia and Schöttler, Mark A. and Bock, Ralph},
title = {The plastid-specific ribosomal proteins of Arabidopsis thaliana can
be divided into non-essential proteins and genuine ribosomal proteins},
journal = {The Plant Journal},
year = {2012},
volume = {69},
pages = {302--316},
number = {2},
abstract = {Plastid translation occurs on bacterial-type 70S ribosomes consisting
of a large (50S) subunit and a small (30S) subunit. The vast majority
of plastid ribosomal proteins have orthologs in bacteria. In addition,
plastids also possess a small set of unique ribosomal proteins, so-called
plastid-specific ribosomal proteins (PSRPs). The functions of these
PSRPs are unknown, but, based on structural studies, it has been
proposed that they may represent accessory proteins involved in translational
regulation. Here we have investigated the functions of five PSRPs
using reverse genetics in the model plant Arabidopsis thaliana. By
analyzing T-DNA insertion mutants and RNAi lines, we show that three
PSRPs display characteristics of genuine ribosomal proteins, in that
down-regulation of their expression led to decreased accumulation
of the 30S or 50S subunit of the plastid ribosomes, resulting in
plastid translational deficiency. In contrast, two other PSRPs can
be knocked out without visible or measurable phenotypic consequences.
Our data suggest that PSRPs fall into two types: (i) PSRPs that have
a structural role in the ribosome and are bona fide ribosomal proteins,
and (ii) non-essential PSRPs that are not required for stable ribosome
accumulation and translation under standard greenhouse conditions.},
doi = {10.1111/j.1365-313X.2011.04791.x},
issn = {1365-313X},
keywords = {chloroplast, translation, ribosome, ribosomal protein, PSRP, plastid-specific
ribosomal protein.},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2011.04791.x}
}
@ARTICLE{Tillett2012,
author = {Tillett, Richard L. and Wheatley, Matthew D. and Tattersall, Elizabeth
A. R. and Schlauch, Karen A. and Cramer, Grant R. and Cushman, John
C.},
title = {The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional
factor enhances freezing tolerance in wine grape},
journal = {Plant Biotechnology Journal},
year = {2012},
volume = {10},
pages = {105--124},
number = {1},
abstract = {Chilling and freezing can reduce significantly vine survival and fruit
set in Vitis vinifera wine grape. To overcome such production losses,
a recently identified grapevine C-repeat binding factor (CBF) gene,
VvCBF4, was overexpressed in grape vine cv. ‘Freedom’ and found
to improve freezing survival and reduced freezing-induced electrolyte
leakage by up to 2 °C in non-cold-acclimated vines. In addition,
overexpression of this transgene caused a reduced growth phenotype
similar to that observed for CBF overexpression in Arabidopsis and
other species. Both freezing tolerance and reduced growth phenotypes
were manifested in a transgene dose-dependent manner. To understand
the mechanistic basis of VvCBF4 transgene action, one transgenic
line (9–12) was genotyped using microarray-based mRNA expression
profiling. Forty-seven and 12 genes were identified in unstressed
transgenic shoots with either a >1.5-fold increase or decrease in
mRNA abundance, respectively. Comparison of mRNA changes with characterized
CBF regulons in woody and herbaceous species revealed partial overlaps,
suggesting that CBF-mediated cold acclimation responses are widely
conserved. Putative VvCBF4-regulon targets included genes with functions
in cell wall structure, lipid metabolism, epicuticular wax formation
and stress-responses suggesting that the observed cold tolerance
and dwarf phenotypes are the result of a complex network of diverse
functional determinants.},
doi = {10.1111/j.1467-7652.2011.00648.x},
issn = {1467-7652},
keywords = {CBF transcription factor, freezing, cold tolerance, dwarf, wine grape,
Vitis vinifera},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1467-7652.2011.00648.x}
}
@ARTICLE{Tilley2009,
author = {Tilley, Ann E. and Harvey, Ben-Gary and Heguy, Adriana and Hackett,
Neil R. and Wang, Rui and O'Connor, Timothy P. and Crystal, Ronald
G.},
title = {Down-regulation of the Notch Pathway in Human Airway Epithelium in
Association with Smoking and Chronic Obstructive Pulmonary Disease},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2009},
volume = {179},
pages = {457--466},
number = {6},
month = mar,
abstract = {Rationale: The airway epithelium of smokers is subject to a variety
of mechanisms of injury with consequent modulation of epithelial
regeneration and disordered differentiation. Several signaling pathways,
including the Notch pathway, control epithelial differentiation in
lung morphogenesis, but little is known about the role of these pathways
in adults. Objectives: We tested the hypotheses that Notch-related
genes are expressed in the normal nonsmoker small airway epithelium
of human adults, and that Notch-related gene expression is down-regulated
in healthy smokers and smokers with chronic obstructive pulmonary
disease (COPD). Methods: We used microarray technology to evaluate
the expression of 55 Notch-related genes in the small airway epithelium
of nonsmokers. We used TaqMan quantitative polymerase chain reaction
(PCR) to confirm the expression of key genes and we used immunohistochemistry
to assess the expression of Notch-related proteins in the airway
epithelium. Changes in expression of Notch genes in healthy smokers
and smokers with COPD compared with nonsmokers were evaluated by
PCR. Measurements and Main Results: Microarray analysis demonstrated
that 45 of 55 Notch-related genes are expressed in the small airway
epithelium of adults. TaqMan PCR confirmed the expression of key
genes with highest expression of the ligand DLL1, the receptor NOTCH2,
and the downstream effector HES1. Immunohistochemistry demonstrated
the expression of Jag1, Notch2, Hes1, and Hes5 in airway epithelium.
Several Notch ligands, receptors, and downstream effector genes were
down-regulated in smokers, with more genes down-regulated in smokers
with COPD than in healthy smokers. Conclusions: These observations
are consistent with the hypothesis that the Notch pathway likely
plays a role in the human adult airway epithelium, with down-regulation
of Notch pathway gene expression in association with smoking and
COPD.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/179/6/457}
}
@ARTICLE{Tilley2007,
author = {Tilley, R.E. and McNeil, C.J. and Ashworth, C.J. and Page, K.R. and
McArdle, H.J.},
title = {Altered muscle development and expression of the insulin-like growth
factor system in growth retarded fetal pigs},
journal = {Domestic Animal Endocrinology},
year = {2007},
volume = {32},
pages = {167--177},
number = {3},
month = apr,
issn = {0739-7240},
keywords = {Growth retardation, IGF, Fetus, Pig, Skeletal muscle},
url = {http://www.sciencedirect.com/science/article/B6T62-4JFGCNX-1/2/aca26ea85fea5905d5a2a1ed173e7e92}
}
@ARTICLE{Tilton2011,
author = {Tilton, Fred A. and Tilton, Susan C. and Bammler, Theo K. and Beyer,
Richard P. and Stapleton, Patricia L. and Scholz, Nathaniel L. and
Gallagher, Evan P.},
title = {Transcriptional impact of organophosphate and metal mixtures on olfaction:
Copper dominates the chlorpyrifos-induced response in adult zebrafish},
journal = {Aquatic Toxicology},
year = {2011},
volume = {102},
pages = {205--215},
number = {3-4},
month = apr,
abstract = {Chemical exposures in fish have been linked to loss of olfaction leading
to an inability to detect predators and prey and decreased survival.
However, the mechanisms underlying olfactory neurotoxicity are not
well characterized, especially in environmental exposures which involve
chemical mixtures. We used zebrafish to characterize olfactory transcriptional
responses by two model olfactory inhibitors, the pesticide chlorpyrifos
(CPF) and mixtures of CPF with the neurotoxic metal copper (Cu).
Microarray analysis was performed on RNA from olfactory tissues of
zebrafish exposed to CPF alone or to a mixture of CPF and Cu. Gene
expression profiles were analyzed using principal component analysis
and hierarchical clustering, whereas gene set analysis was used to
identify biological themes in the microarray data. Microarray results
were confirmed by real-time PCR on genes serving as potential biomarkers
of olfactory injury. In addition, we mined our previously published
Cu-induced zebrafish olfactory transcriptional response database
(Tilton et al., 2008) for the purposes of discriminating pathways
of olfaction impacted by either the individual agents or the CPF-Cu
mixture transcriptional signatures. CPF exposure altered the expression
of gene pathways associated with cellular morphogenesis and odorant
binding, but not olfactory signal transduction, a known olfactory
pathway for Cu. The mixture profiles shared genes from the Cu and
CPF datasets, whereas some genes were altered only by the mixtures.
The transcriptional signature of the mixtures was more similar to
that in zebrafish exposed to Cu alone than for CPF. In conclusion,
exposure to a mixture containing a common environmental metal and
pesticide causes a unique transcriptional signature that is heavily
influenced by the metal, even when organophosphate predominates.},
issn = {0166-445X},
keywords = {Copper, Chlorpyrifos, Organophosphate pesticide, Zebrafish, Olfaction,
Toxicity, Mixtures},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X11000191}
}
@ARTICLE{Tilton2008,
author = {Tilton, Fred and Tanguay, Robert L.},
title = {Exposure to Sodium Metam during Zebrafish Somitogenesis Results in
Early Transcriptional Indicators of the Ensuing Neuronal and Muscular
Dysfunction},
journal = {Toxicol. Sci.},
year = {2008},
volume = {106},
pages = {103--112},
number = {1},
month = nov,
abstract = {Exposures to sodium metam (NaM) within the developmental period of
somitogenesis (10- to 18-h postfertilization [hpf]) results in easily
detectable distortions of the notochord by 24 hpf in the developing
zebrafish. We hypothesized that NaM-induced transcriptional changes
during somitogenesis would reveal the major molecular targets in
the zebrafish embryo. Embryos were exposed to NaM beginning at 4
hpf (1000 cells) and total RNA was isolated from embryos at the 3
somite (11 hpf), 10 somite (14 hpf), 18 somite (18 hpf), and larval
(24 hpf) stages of development. Using the Affymetrix zebrafish gene
array we observed relatively few mRNAs differentially regulated at
least twofold at each time point (11 hpf, 101 genes; 14 hpf, 151;
18 hpf, 154; 24 hpf, 33). The transcriptional profiles reveal neurodevelopment
and myogenesis as the two primary targets of NaM developmental exposure.
Quantitative PCR of several muscle and neuronal genes confirmed the
array response. We also followed the structural development of the
peripheral nervous system under NaM exposure using antibodies against
neuronal structural proteins. Although there was no change in the
onset of antibody staining, profound alterations became apparent
during the period in which the notochord becomes distorted (> 18
hpf). Motor neuron development observed with the Tg(NBT:MAPT-GFP)zc1
transgenic zebrafish and a primary motor neuron specific antibody
showed similar timing in the structural alterations observed in these
cell types. Further study of the interactions of dithiocarbamates
with the regulatory elements of fast muscle development and neurodevelopment
is warranted.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/106/1/103}
}
@ARTICLE{Tilton2006,
author = {Tilton, Susan C. and Givan, Scott A. and Pereira, Cliff B. and Bailey,
George S. and Williams, David E.},
title = {Toxicogenomic Profiling of the Hepatic Tumor Promoters Indole-3-Carbinol,
17{beta}-Estradiol and {beta}-Naphthoflavone in Rainbow Trout},
journal = {Toxicol. Sci.},
year = {2006},
volume = {90},
pages = {61--72},
number = {1},
month = mar,
abstract = {Indole-3-carbinol (I3C), from cruciferous vegetables, has been found
to suppress or enhance tumors in several animal models. We previously
reported that dietary I3C promotes hepatocarcinogenesis in rainbow
trout (Oncorhynchus mykiss) at concentrations that differentially
activated estrogen receptor (ER) or aryl hydrocarbon receptor (AhR)-mediated
responses based on individual protein biomarkers. In this study,
we evaluated the relative importance of these pathways as potential
mechanisms for I3C on a global scale. Hepatic gene expression profiles
were examined in trout after dietary exposure to 500 and 1500 ppm
I3C and 3,3'-diindolylmethane (DIM), a major in vivo component of
I3C, and were compared to the transcriptional signatures of two model
hepatic tumor promoters: 17{beta}-estradiol (E2), an ER agonist,
and {beta}-naphthoflavone, an AhR agonist. We demonstrate that I3C
and DIM acted similar to E2 at the transcriptional level based on
correlation analysis of expression profiles and clustering of gene
responses. Of the genes regulated by E2 (fold change [≥]2.0 or
[≤]0.50), most genes were regulated similarly by DIM (87-92%)
and I3C (71%), suggesting a common mechanism of action. Of interest
were upregulated genes associated with signaling pathways for cell
growth and proliferation, vitellogenesis, and protein folding, stability,
and transport. Other genes downregulated by E2, including those involved
in acute-phase immune response, were also downregulated by DIM and
I3C. Gene regulation was confirmed by qRT-PCR and Western blot. These
data indicate I3C promotes hepatocarcinogenesis through estrogenic
mechanisms in trout liver and suggest DIM may be an even more potent
hepatic tumor promoter in this model.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/90/1/61}
}
@ARTICLE{Timke2008,
author = {Timke, Carmen and Zieher, Heike and Roth, Alexandra and Hauser, Kai
and Lipson, Kenneth E. and Weber, Klaus J. and Debus, Jurgen and
Abdollahi, Amir and Huber, Peter E.},
title = {Combination of Vascular Endothelial Growth Factor Receptor/Platelet-Derived
Growth Factor Receptor Inhibition Markedly Improves Radiation Tumor
Therapy},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {2210--2219},
number = {7},
month = apr,
abstract = {Purpose: Investigations on the combination of radiotherapy with vascular
endothelial growth factor (VEGF) and platelet-derived growth factor
(PDGF) antiangiogenic agents, which has the potential to improve
the clinical outcome in cancer patients. Experimental Design: Here,
we analyze the combined VEGF (SU5416) and PDGF (SU6668) receptor
tyrosine kinase inhibition with irradiation in human endothelium
(HUVEC), prostate cancer (PC3), and glioblastoma (U87) in vitro and
in vivo. Results: Combined inhibition of VEGF and PDGF signaling
resulted in enhanced apoptosis, reduced cell proliferation, and clonogenic
survival as well as reduced endothelial cell migration and tube formation
compared with single pathway inhibition. These effects were further
enhanced by additional irradiation. Likewise, in PC3 and U87 tumors
growing s.c. on BALB/c nu/nu mice, dual inhibition of VEGF and PDGF
signaling significantly increased tumor growth delay versus each
monotherapy. Interestingly, radiation at [~]20% of the dose necessary
to induce local tumor control exerts similar tumor growth-inhibitory
effects as the antiangiogenic drugs given at their maximum effective
dose. Addition of radiotherapy to both mono- as well as dual-antiangiogenic
treatment markedly increased tumor growth delay. With respect to
tumor angiogenesis, radiation further decreased microvessel density
(CD31 count) and tumor cell proliferation (Ki-67 index) in all drug-treated
groups. Of note, the slowly growing PC3 tumor responded better to
the antiangiogenic drug treatments than the faster-growing U87 tumor.
In addition to the beneficial effect of abrogating VEGF survival
signaling when combined with radiation, we identified here a novel
mechanism for the tumor escape from radiation damage. We found that
radiation induced up-regulation of all four isoforms of PDGF (A-D)
in endothelial cells supporting adjacent smooth muscle cells resulting
in a prosurvival effect of radiation. The addition of SU6668 attenuated
this undesirable paracrine radiation effect, which may rationalize
the combined application of radiation with PDGF signaling inhibition
to increase antitumor effects. Conclusion: A relative low radiation
dose markedly enhances local antitumor effects of combined VEGF and
PDGF signaling inhibition, suggesting a promising combination regimen
for local tumor treatment with radiotherapy remaining an essential
element.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/7/2210}
}
@ARTICLE{Timmerhaus2011,
author = {Timmerhaus, Gerrit and Krasnov, Aleksei and Nilsen, Pal and Alarcon,
Marta and Afanasyev, Sergey and Rode, Marit and Takle, Harald and
Jorgensen, Sven},
title = {Transcriptome profiling of immune responses to cardiomyopathy syndrome
(CMS) in Atlantic salmon},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {459},
number = {1},
abstract = {BACKGROUND:Cardiomyopathy syndrome (CMS) is a disease associated with
severe myocarditis primarily in adult farmed Atlantic salmon (Salmo
salar L.), caused by a double-stranded RNA virus named piscine myocarditis
virus (PMCV) with structural similarities to the Totiviridae family.
Here we present the first characterisation of host immune responses
to CMS assessed by microarray transcriptome profiling.RESULTS:Unvaccinated
farmed Atlantic salmon post-smolts were infected by intraperitoneal
injection of PMCV and developed cardiac pathology consistent with
CMS. From analysis of heart samples at several time points and different
tissues at early and clinical stages by oligonucleotide microarrays
(SIQ2.0 chip), six gene sets representing a broad range of immune
responses were identified, showing significant temporal and spatial
regulation. Histopathological examination of cardiac tissue showed
myocardial lesions from 6 weeks post infection (wpi) that peaked
at 8-9 wpi and was followed by a recovery. Viral RNA was detected
in all organs from 4 wpi suggesting a broad tissue tropism. High
correlation between viral load and cardiac histopathology score suggested
that cytopathic effect of infection was a major determinant of the
myocardial changes. Strong and systemic induction of antiviral and
IFN-dependent genes from 2 wpi that levelled off during infection,
was followed by a biphasic activation of pathways for B cells and
MHC antigen presentation, both peaking at clinical pathology. This
was preceded by a distinct cardiac activation of complement at 6
wpi, suggesting a complement-dependent activation of humoral Ab-responses.
Peak of cardiac pathology and viral load coincided with cardiac-specific
upregulation of T cell response genes and splenic induction of complement
genes. Preceding the reduction in viral load and pathology, these
responses were probably important for viral clearance and recovery.CONCLUSIONS:By
comparative analysis of gene expression, histology and viral load,
the temporal and spatial regulation of immune responses were characterised
and novel immune genes identified, ultimately leading to a more complete
understanding of host-virus responses and pathology and protection
in Atlantic salmon during CMS.},
doi = {10.1186/1471-2164-12-459},
issn = {1471-2164},
pubmedid = {21943289},
url = {http://www.biomedcentral.com/1471-2164/12/459}
}
@ARTICLE{Timmermans2009,
author = {Timmermans, M. J. T. N. and Roelofs, D. and Nota, B. and Ylstra,
B. and Holmstrup, M.},
title = {Sugar sweet springtails: on the transcriptional response of Folsomia
candida (Collembola) to desiccation stress},
journal = {Insect Molecular Biology},
year = {2009},
volume = {18},
pages = {737--746},
number = {6},
abstract = {Abstract Several species of Collembola survive stressful desiccating
conditions by absorbing water vapour from the environment. To obtain
insight into the transcriptomic responses underlying this ‘water
vapour absorption’ mechanism we subjected Folsomia candida (Collembola)
to transcriptome profiling. We show that ecologically relevant desiccation
stress leads to strong time-dependent transcriptomic changes. Exposure
of F. candida to 98.2% relative humidity over an interval of 174Â h
resulted in a high number of gene transcripts being differentially
expressed (up to 41%; P-value < 0.05). Additional Gene Ontology
analyses suggest that carbohydrate transport, sugar catabolism and
cuticle maintenance are biological processes involved in combating
desiccation. However, many additional pathways seem to be affected;
additional experiments are needed to elucidate which responses are
primarily linked to desiccation resistance.},
issn = {1365-2583},
keywords = {transcription profiling, Folsomia candida, desiccation, water vapour
absorption},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2583.2009.00916.x}
}
@ARTICLE{Timmons2006,
author = {Timmons, James A. and Sundberg, Carl Johan},
title = {Oligonucleotide microarray expression profiling: Human skeletal muscle
phenotype and aerobic exercise training},
journal = {IUBMB Life},
year = {2006},
volume = {58},
pages = {15--24},
number = {1},
abstract = {Abstract 10.1080/15216540500507390.abs Regular aerobic exercise reduces
risk of cardiovascular disease far more effectively than any pharmaceutical
agent. The precise mechanisms contributing to these health benefits
are unknown. Currently, much of our knowledge regarding the molecular
regulators of skeletal muscle phenotype remodeling in response to
muscle activity is derived from rodent models. Over the past five
years large scale gene analysis has emerged as a promising research
strategy for studying complex processes in human tissue. This review
will principally discuss the application of large scale gene expression
profiling to study the molecular responses to longitudinal aerobic
exercise training studies in humans. The focus is largely on the
Affymetrix technology platform, as this can be most easily compared,
in a quantitative manner, across laboratories. Indeed, there are
compelling reasons to adopt a common standard to obtain maximum synergy
across complex, expensive and invasive human studies. Direct comparisons
between array data sets can be made, and these should be considered
novel 'experiments', often providing great insight into disease mechanisms.
Weaknesses in existing human studies are identified and future objectives
are discussed. IUBMB Life, 58: 15 - 24, 2006},
issn = {1521-6551},
keywords = {Affymetrix, transcriptome, endurance performance, gene, microarray,
skeletal muscle},
publisher = {Informa Healthcare},
url = {http://dx.doi.org/10.1080/15216540500507390}
}
@ARTICLE{Ting2008,
author = {Ting, Angela H. and Suzuki, Hiromu and Cope, Leslie and Schuebel,
Kornel E. and Lee, Byron H. and Toyota, Minoru and Imai, Kohzoh and
Shinomura, Yasuhisa and Tokino, Takashi and Baylin, Stephen B.},
title = {A Requirement for DICER to Maintain Full Promoter CpG Island Hypermethylation
in Human Cancer Cells},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {2570--2575},
number = {8},
month = apr,
abstract = {Promoter hypermethylation is a prevalent phenomenon, found in virtually
all cancer types studied thus far, and accounts for tumor suppressor
gene silencing in the absence of genetic mutations. The mechanism
behind the establishment and maintenance of such aberrant hypermethylation
has been under intense study. Here, we have uncovered a link between
aberrant gene silencing associated with promoter CpG island DNA methylation
and the siRNA/miRNA processing enzyme, DICER, in human cancer cells.
By comparing demethylated HCT116 colon cancer cells with HCT116 cells
genetically rendered hypomorphic for DICER, we identified a group
of epigenetically silenced genes that became reactivated in the absence
of functional DICER. This reactivation is associated with a dramatic
loss of localized promoter DNA hypermethylation. Thus, intact DICER
is required to maintain full promoter DNA hypermethylation of select
epigenetically silenced loci in human cancer cells. [Cancer Res 2008;68(8):2570-5]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/8/2570}
}
@ARTICLE{Tingaud-Sequeira2009,
author = {Tingaud-Sequeira, Angèle and Chauvigné, François and Lozano, Juanjo
and Agulleiro, María and Asensio, Esther and Cerdà, Joan},
title = {New insights into molecular pathways associated with flatfish ovarian
development and atresia revealed by transcriptional analysis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {434},
number = {1},
abstract = {BACKGROUND:The Senegalese sole (Solea senegalensis) is a marine flatfish
of increasing commercial interest. However, the reproduction of this
species in captivity is not yet controlled mainly because of the
poor knowledge on its reproductive physiology, as it occurs for other
non-salmonid marine teleosts that exhibit group-synchronous ovarian
follicle development. In order to investigate intra-ovarian molecular
mechanisms in Senegalese sole, the aim of the present study was to
identify differentially expressed genes in the ovary during oocyte
growth (vitellogenesis), maturation and ovarian follicle atresia
using a recently developed oligonucleotide microarray.RESULTS:Microarray
analysis led to the identification of 118 differentially expressed
transcripts, of which 20 and 8 were monitored by real-time PCR and
in situ hybridization, respectively. During vitellogenesis, many
up-regulated ovarian transcripts had putative mitochondrial function/location
suggesting high energy production (NADH dehydrogenase subunits, cytochromes)
and increased antioxidant protection (selenoprotein W2a), whereas
other regulated transcripts were related to cytoskeleton and zona
radiata organization (zona glycoprotein 3, alpha and beta actin,
keratin 8), intracellular signalling pathways (heat shock protein
90, Ras homolog member G), cell-to-cell and cell-to-matrix interactions
(beta 1 integrin, thrombospondin 4b), and the maternal RNA pool (transducer
of ERBB2 1a, neurexin 1a). Transcripts up-regulated in the ovary
during oocyte maturation included ion transporters (Na+-K+-ATPase
subunits), probably required for oocyte hydration, as well as a proteinase
inhibitor (alpha-2-macroglobulin) and a vesicle calcium sensor protein
(extended synaptotagmin-2-A). During follicular atresia, few transcripts
were found to be up-regulated, but remarkably most of them were localized
in follicular cells of atretic follicles, and they had inferred roles
in lipid transport (apolipoprotein C-I), chemotaxis (leukocyte cell-derived
chemotaxin 2,), angiogenesis (thrombospondin), and prevention of
apoptosis (S100a10 calcium binding protein).CONCLUSION:This study
has identified a number of differentially expressed genes in the
ovary that were not previously found to be regulated during ovarian
development in marine fish. Specifically, we found evidence, for
the first time in teleosts, of the activation of chemoattractant,
angiogenic and antiapoptotic pathways in hypertrophied follicular
cells at the onset of ovarian atresia.},
doi = {10.1186/1471-2164-10-434},
issn = {1471-2164},
pubmedid = {19754951},
url = {http://www.biomedcentral.com/1471-2164/10/434}
}
@ARTICLE{Tinwell2011,
author = {Tinwell, H. and Rascle, J. B. and Colombel, S. and Al Khansa, I.
and Freyberger, A. and Bars, R.},
title = {A novel method for measuring aromatase activity in tissue samples
by determining estradiol concentrations},
journal = {Journal of Applied Toxicology},
year = {2011},
volume = {31},
pages = {446--454},
number = {5},
abstract = {Increasing scrutiny of endocrine disrupters has led to changes to
European pesticide and biocide legislation and to the introduction
of the Endocrine Disrupter Screening Program by the US EPA. One element
of endocrine disrupter identification is to determine its effects
on aromatase, but most available assays are limited as they depend
on tritiated water production to indicate enzyme activity. Whilst
acceptable for determining aromatase effects using a cell-free approach,
this method is unreliable for cell or tissue-based investigations
as other cytochrome P-450 isoenzyme activities can similarly produce
tritiated water and consequently confound interpretation of the aromatase
data. To address this lack of specificity an assay directly measuring
the final estrogen product by incubating rat tissue protein with
testosterone and measuring the resultant estradiol concentration
was developed. Using this approach we demonstrated marked increases
in enzyme activity in pregnant rat ovary samples and dose-related
inhibitions when incubating non-pregnant rat ovary samples with known
aromatase inhibitors. Hepatic aromatase activity was investigated
using our method and by tritiated water production with microsomes
from rats dosed with the antiandrogen 1,1-dichloro-2,2-bis(4 chlorophenyl)ethane.
Additional cytochrome P-450s were also measured. Treatment-related
increased tritiated water production and general hepatic enzyme activity
were recorded but estradiol was not increased, indicating that the
increased tritiated water was due to general enzyme activity and
not aromatase activity. A simple and specific method has been developed
that can detect aromatase inhibition and induction, which when applied
to tissue samples, provides a means of generating relevant animal
data concerning chemical effects on the aromatase enzyme.},
doi = {10.1002/jat.1623},
issn = {1099-1263},
keywords = {aromatase, endocrine disruption, estradiol, liver, 1,1-dichloro-2,2-bis(4
chlorophenyl)ethane (DDE)},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/jat.1623}
}
@ARTICLE{TiongOng2003,
author = {Tiong Ong, S. and Ly, Chi and Nguyen, Mark and Kay Brightman, B.
and Fan, Hung},
title = {Expression profiling of a transformed thymocyte cell line undergoing
maturation in vitro identifies multiple genes involved in positive
selection},
journal = {Cellular Immunology},
year = {2003},
volume = {221},
pages = {64--79},
number = {1},
month = jan,
abstract = {Biochemical and genetic studies of thymocyte maturation would be facilitated
by the development of cultured cell lines that reflect stages of
positive selection. We have derived a CD4+CD8+TCR+ T-lymphoid cell
line (M20) from a murine thymic tumor induced by a retrovirus carrying
the v-myc oncogene (M-MuLV(myc)). M20 subclones undergo several aspects
of positive selection in response to co-culture with a thymic stromal
cell line (St3), including down-regulation of CD4 and CD8, and up-regulation
of CD5 and TCR. M20 possesses a functional TCR complex, and ligation
of this complex produces changes similar to co-culture with St3 stroma.
Expression profiling of M20 cells in this system identified 23 genes
previously shown to be important in thymocyte maturation, as well
as several novel candidate genes. This system provides a new model
to elucidate the molecular mechanisms of thymocyte maturation and
TCR-mediated cell signaling in double-positive thymocytes.},
issn = {0008-8749},
keywords = {Thymocyte, Gene expression, Maturation},
url = {http://www.sciencedirect.com/science/article/B6WCF-4893XYY-6/2/02015fab27ed43fdcd7f38c2b1388527}
}
@ARTICLE{Tirosh2011,
author = {Tirosh, Itay and Wong, Koon Ho and Barkai, Naama and Struhl, Kevin},
title = {Extensive divergence of yeast stress responses through transitions
between induced and constitutive activation},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {16693-16698},
number = {40},
abstract = {Closely related species show a high degree of differences in gene
expression, but the functional significance of these differences
remains unclear. Similarly, stress responses in yeast typically involve
differential expression of numerous genes, and it is unclear how
many of these are functionally significant. To address these issues,
we compared the expression programs of four yeast species under different
growth conditions, and found that the response of these species to
stress has diverged extensively. On an individual gene basis, most
transcriptional responses are not conserved in any pair of species,
and there are very limited common responses among all four species.
We present evidence that many evolutionary changes in stress responses
are compensated either (i) by the response of related genes or (ii)
by changes in the basal expression levels of the genes whose responses
have diverged. Thus, stress-related genes are often induced upon
stress in some species but maintain high levels even in the absence
of stress at other species, indicating a transition between induced
and constitutive activation. In addition, [~]15% of the stress responses
are specific to only one of the four species, with no evidence for
compensating effects or stress-related annotations, and these may
reflect fortuitous regulation that is unimportant for the stress
response (i.e., biological noise). Frequent compensatory changes
and biological noise may explain how diverged expression responses
support similar physiological responses.},
doi = {10.1073/pnas.1113718108},
eprint = {http://www.pnas.org/cgi/reprint/108/40/16693.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/40/16693}
}
@ARTICLE{Tisserand2011,
author = {Tisserand, Johan and Khetchoumian, Konstantin and Thibault, Christelle
and Dembele, Doulaye and Chambon, Pierre and Losson, Regine},
title = {Tripartite Motif 24 (Trim24/Tif1{alpha}) Tumor Suppressor Protein
Is a Novel Negative Regulator of Interferon (IFN)/Signal Transducers
and Activators of Transcription (STAT) Signaling Pathway Acting through
Retinoic Acid Receptor {alpha} (Rar{alpha}) Inhibition},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {33369-33379},
number = {38},
abstract = {Recent genetic studies in mice have established that the nuclear receptor
coregulator Trim24/Tif1 suppresses hepatocarcinogenesis by inhibiting
retinoic acid receptor (Rara)-dependent transcription and cell proliferation.
However, Rara targets regulated by Trim24 remain unknown. We report
that the loss of Trim24 resulted in interferon (IFN)/STAT pathway
overactivation soon after birth (week 5). Despite a transient attenuation
of this pathway by the induction of several IFN/STAT pathway repressors
later in the disease, this phenomenon became more pronounced in tumors.
Remarkably, Rara haplodeficiency, which suppresses tumorigenesis
in Trim24-/- mice, prevented IFN/STAT overactivation. Moreover, together
with Rara, Trim24 bound to the retinoic acid-responsive element of
the Stat1 promoter and repressed its retinoic acid-induced transcription.
Altogether, these results identify Trim24 as a novel negative regulator
of the IFN/STAT pathway and suggest that this repression through
Rara inhibition may prevent liver cancer.},
doi = {10.1074/jbc.M111.225680},
eprint = {http://www.jbc.org/cgi/reprint/286/38/33369.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/38/33369}
}
@ARTICLE{Tisserand2003,
author = {Tisserand, Pascaline and Fouquet, Coralie and Marck, Veronique and
Mallard, Christine and Fabre, Monique and Vielh, Philippe and Soussi,
Thierry},
title = {ThinPrep®-processed fine-needle samples of breast are effective material
for RNA- and DNA-based molecular diagnosis},
journal = {Cancer},
year = {2003},
volume = {99},
pages = {223--232},
number = {4},
abstract = {Abstract 10.1002/cncr.11258.abs BACKGROUND Fine-needle sampling is
the least invasive method of in vivo breast carcinoma sampling and
can provide material for breast carcinoma diagnosis. The aim of the
current study was to assess the accuracy of molecular diagnosis techniques
using fine-needle sample (FNS) material stored in PreservCyt® (Cytyc
Corp., Boxborough, MA). METHODS The p53 tumor suppressor gene was
chosen as a model because it can be used for DNA, RNA, and protein
analysis. Molecular analysis was performed using a yeast functional
assay and DNA sequencing. p53 accumulation was evaluated by immunocytochemistry.
RESULTS DNA and protein analysis indicated that samples stored for
periods of several months, either at room temperature, 4 °C, or
−20 °C, can be processed reliably. For RNA-based diagnosis, samples
were still intact after 5 months of storage in PreservCyt® at 4
°C. In addition, using FNS material that was stored for 16 months
at 4 °C, the authors detected p53 mutations with either the functional
assay for separating alleles in yeast (an RNA-based functional assay)
or direct cDNA sequencing. CONCLUSIONS Fine-needle samples stored
in PreservCyt® at 4 °C are very good material for molecular diagnosis
techniques. In addition, it is feasible to adopt a strategy of storing
excess FNS material to create cellular banks that will be invaluable
for future gene studies. Cancer (Cancer Cytopathol) 2003;99:223–32.
© 2003 American Cancer Society.DOI 10.1002/cncr.11258},
issn = {1097-0142},
keywords = {fine-needle sampling, cytology, p53 tumor suppressor gene, ThinPrep®,
molecular diagnosis, immunocytochemistry, cellular banking},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.11258}
}
@ARTICLE{Tissing2007,
author = {Tissing, Wim J. E. and den Boer, Monique L. and Meijerink, Jules
P. P. and Menezes, Renee X. and Swagemakers, Sigrid and van der Spek,
Peter J. and Sallan, Stephen E. and Armstrong, Scott A. and Pieters,
Rob},
title = {Genomewide identification of prednisolone-responsive genes in acute
lymphoblastic leukemia cells},
journal = {Blood},
year = {2007},
volume = {109},
pages = {3929--3935},
number = {9},
month = may,
abstract = {Glucocorticoids are keystone drugs in the treatment of childhood acute
lymphoblastic leukemia (ALL). To get more insight in signal transduction
pathways involved in glucocorticoid-induced apoptosis, Affymetrix
U133A GeneChips were used to identify transcriptionally regulated
genes on 3 and 8 hours of prednisolone exposure in leukemic cells
of 13 children as compared with nonexposed cells. Following 3 hours
of exposure no significant changes in gene expression could be identified.
Following 8 hours of exposure, 51 genes were differentially expressed
(P < .001 and false discovery rate < 10%) with 39 genes being up-regulated
(median, 2.4-fold) and 12 genes were down-regulated (median, 1.7-fold).
Twenty-one of those genes have not been identified before to be transcriptionally
regulated by prednisolone. Two of the 3 most highly up-regulated
genes were tumor suppressor genes, that is, thioredoxin-interacting
protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing
16 (ZBTB16; 8.8-fold). About 50% of the differentially expressed
genes were functionally categorized in 3 major routes, namely MAPK
pathways (9 genes), NF-{kappa}B signaling (11 genes), and carbohydrate
metabolism (5 genes). Biologic characterization of these genes and
pathways might elucidate the action of glucocorticoids in ALL cells,
possibly suggesting causes of glucocorticoid resistance and new potential
targets for therapy.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/9/3929}
}
@ARTICLE{Titgemeyer2011,
author = {E.C. Titgemeyer and L.K. Mamedova and K.S. Spivey and J.K. Farney
and B.J. Bradford},
title = {An unusual distribution of the niacin receptor in cattle},
journal = {Journal of Dairy Science},
year = {2011},
volume = {94},
pages = {4962 - 4967},
number = {10},
abstract = {Responses to pharmacological doses of niacin, an agonist for GPR109A
(niacin receptor), were different in cattle than in humans and rodents.
Thus, the tissue distribution of GPR109A was investigated in cattle.
Samples of tail head fat, back fat, perirenal fat, longissimus muscle,
and liver were analyzed for abundance of GPR109A mRNA by quantitative
real-time reverse transcription-PCR and for abundance of GPR109A
protein by Western blotting. Niacin receptor transcript and protein
were detected in all tissues analyzed. The mRNA for GPR109A was more
abundant in liver than in the other tissues sampled (GPR109A:RPS9
mRNA abundance = 0.56 in liver compared with 0.06 in longissimus
muscle, 0.15 in kidney fat, 0.11 in back fat, 0.23 in tail head fat;
standard error of the mean = 0.028). Additionally, mRNA
for GPR109A was found (GPR109A:RPS9 mRNA abundance ≥0.004) in each
of the 5 regions of bovine brain that were analyzed: cerebral cortex,
cerebellum, thalamus, hypothalamus, and brain stem. Evaluation of
liver tissue by immunofluorescence suggested that GPR109A was expressed
in parenchymal cells and not localized exclusively to immune-system
cells. Finally, analysis of the putative bovine GPR109A sequence
verified that AA residues required for binding niacin in human GPR109A
are conserved, suggesting that the bovine sequence identified encodes
a functional niacin receptor. The identification of GPR109A in bovine
liver, muscle, and brain is a novel finding.},
doi = {10.3168/jds.2011-4193},
issn = {0022-0302},
keywords = {nicotinic acid},
url = {http://www.sciencedirect.com/science/article/pii/S0022030211005170}
}
@ARTICLE{Titos2010,
author = {Titos, Esther and Ferré, Natàlia and Lozano, Juan José and Horrillo,
Raquel and López-Parra, Marta and Arroyo, Vicente and Clària, Joan},
title = {Protection from hepatic lipid accumulation and inflammation by genetic
ablation of 5-lipoxygenase},
journal = {Prostaglandins \& Other Lipid Mediators},
year = {2010},
volume = {92},
pages = {54--61},
number = {1-4},
month = jun,
abstract = {Five-lipoxygenase (5-LO) has been postulated as a pathogenic factor
in liver injury. Indeed, Alox5, the gene coding for 5-LO, is heavily
over-expressed in experimental liver disease, in which 5-LO inhibition
consistently ameliorates hepatic steatosis, inflammation and fibrosis.
Herein, we report the findings in mice with targeted deletion of
Alox5 as a proof of concept of the role of 5-LO in liver injury.
Our findings demonstrate that ablation of Alox5 in mice confers protection
against carbon tetrachloride-induced liver injury since hepatic necroinflammation,
inflammatory infiltrate, hepatocyte ballooning and serum ALT levels
were significantly reduced in Alox5-deficient mice. These mice also
showed a lower degree of hepatic steatosis, which affected micro-
and macrosteatosis to a similar extent. Moreover, microarray analysis
revealed a differential profile of hepatic gene expression in Alox5-deficient
mice, with a total of 117 genes differentially expressed in these
animals. Functional grouping of these genes revealed that 28 (approximately
24% of total changes) were related to the category of lipid metabolism,
including the lipogenic factors Lpin1, C/EBP, Fasn, Acly and Elovl6.
Moreover, Ingenuity Pathway Analysis revealed lipid metabolism as
the molecular/cellular function most affected by the loss of Alox5.
These findings confirm at a genetic level that Alox5 plays a pathogenic
role in the response of the liver to injury.},
issn = {1098-8823},
keywords = {5-Lipoxygenase, Knockout mice, Lipid metabolism},
url = {http://www.sciencedirect.com/science/article/B6T3H-4YKGJC0-1/2/c2833c1909e51f637a11ea354d57fe30}
}
@ARTICLE{Titos2011,
author = {Titos, Esther and Rius, Bibiana and Gonzalez-Periz, Ana and Lopez-Vicario,
Cristina and Moran-Salvador, Eva and Martinez-Clemente, Marcos and
Arroyo, Vicente and Claria, Joan},
title = {Resolvin D1 and Its Precursor Docosahexaenoic Acid Promote Resolution
of Adipose Tissue Inflammation by Eliciting Macrophage Polarization
toward an M2-Like Phenotype},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {5408-5418},
number = {10},
abstract = {We recently demonstrated that {omega}-3-polyunsaturated fatty acids
ameliorate obesity-induced adipose tissue inflammation and insulin
resistance. In this study, we report novel mechanisms underlying
{omega}-3-polyunsaturated fatty acid actions on adipose tissue, adipocytes,
and stromal vascular cells (SVC). Inflamed adipose tissue from high-fat
diet-induced obese mice showed increased F4/80 and CD11b double-positive
macrophage staining and elevated IL-6 and MCP-1 levels. Docosahexaenoic
acid (DHA; 4 g/g) did not change the total number of macrophages
but significantly reduced the percentage of high CD11b/high F4/80-expressing
cells in parallel with the emergence of low-expressing CD11b/F4/80
macrophages in the adipose tissue. This effect was associated with
downregulation of proinflammatory adipokines in parallel with increased
expression of IL-10, CD206, arginase 1, resistin-like molecule ,
and chitinase-3 like protein, indicating a phenotypic switch in macrophage
polarization toward an M2-like phenotype. This shift was confined
to the SVC fraction, in which secretion of Th1 cytokines (IL-6, MCP-1,
and TNF-) was blocked by DHA. Notably, resolvin D1, an anti-inflammatory
and proresolving mediator biosynthesized from DHA, markedly attenuated
IFN-{gamma}/LPS-induced Th1 cytokines while upregulating arginase
1 expression in a concentration-dependent manner. Resolvin D1 also
stimulated nonphlogistic phagocytosis in adipose SVC macrophages
by increasing both the number of macrophages containing ingested
particles and the number of phagocytosed particles and by reducing
macrophage reactive oxygen species production. No changes in adipocyte
area and the phosphorylation of hormone-sensitive lipase, a rate-limiting
enzyme regulating adipocyte lipolysis, were observed. These findings
illustrate novel mechanisms through which resolvin D1 and its precursor
DHA confer anti-inflammatory and proresolving actions in inflamed
adipose tissue.},
doi = {10.4049/jimmunol.1100225},
eprint = {http://www.jimmunol.org/cgi/reprint/187/10/5408.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/10/5408}
}
@ARTICLE{Titus2009,
author = {Titus, Mark A. and Tan, Jiann-an and Gregory, Christopher W. and
Ford, O. Harris and Subramanian, Romesh R. and Fu, Haian and Wilson,
Elizabeth M. and Mohler, James L. and French, Frank S.},
title = {14-3-3{eta} Amplifies Androgen Receptor Actions in Prostate Cancer},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {7571--7581},
number = {24},
month = dec,
abstract = {Purpose: Androgen receptor abundance and androgen receptor-regulated
gene expression in castration-recurrent prostate cancer are indicative
of androgen receptor activation in the absence of testicular androgen.
Androgen receptor transactivation of target genes in castration-recurrent
prostate cancer occurs in part through mitogen signaling that amplifies
the actions of androgen receptor and its coregulators. Herein we
report on the role of 14-3-3{eta} in androgen receptor action. Experimental
Design and Results: Androgen receptor and 14-3-3{eta} colocalized
in COS cell nuclei with and without androgen, and 14-3-3{eta} promoted
androgen receptor nuclear localization in the absence of androgen.
14-3-3{eta} interacted with androgen receptor in cell-free binding
and coimmunoprecipitation assays. In the recurrent human prostate
cancer cell line, CWR-R1, native endogenous androgen receptor transcriptional
activation was stimulated by 14-3-3{eta} at low dihydrotestosterone
concentrations and was increased by epidermal growth factor. Moreover,
the dihydrotestosterone- and epidermal growth factor-dependent increase
in androgen receptor transactivation was inhibited by a dominant
negative 14-3-3{eta}. In the CWR22 prostate cancer xenograft model,
14-3-3{eta} expression was increased by androgen, suggesting a feed-forward
mechanism that potentiates both 14-3-3{eta} and androgen receptor
actions. 14-3-3{eta} mRNA and protein decreased following castration
of tumor-bearing mice and increased in tumors of castrate mice after
treatment with testosterone. CWR22 tumors that recurred 5 months
after castration contained 14-3-3{eta} levels similar to the androgen-stimulated
tumors removed before castration. In a human prostate tissue microarray
of clinical specimens, 14-3-3{eta} localized with androgen receptor
in nuclei, and the similar amounts expressed in castration-recurrent
prostate cancer, androgen-stimulated prostate cancer, and benign
prostatic hyperplasia were consistent with androgen receptor activation
in recurrent prostate cancer. Conclusion: 14-3-3{eta} enhances androgen-
and mitogen-induced androgen receptor transcriptional activity in
castration-recurrent prostate cancer. (Clin Cancer Res 2009;15(24):7571-81)},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/24/7571}
}
@ARTICLE{Tiu2006,
author = {Tiu, Jeremy and Li, Hongli and Rassekh, Christopher and van der Sloot,
Paul and Kovach, Rodney and Zhang, Peilin},
title = {Molecular Basis of Posttransplant Squamous Cell Carcinoma: The Potential
Role of Cyclosporine A in Carcinogenesis},
journal = {The Laryngoscope},
year = {2006},
volume = {116},
pages = {762--769},
number = {5},
abstract = {Abstract 10.1097/01.mlg.0000205170.24517.28.abs Cyclosporine (CSA)
is a widely used immunosuppressive agent, predominantly for transplant
patients. It is well recognized that transplant patients are prone
to develop squamous carcinoma of the skin and mucosa, and this high
incidence of squamous carcinoma in the transplant population cannot
be explained by immunosuppression alone. We hypothesize that CSA
may play a significant role in the transformation of normal epidermal
squamous cells to carcinoma. CSA is a specific ligand for calcineurin,
a ubiquitously expressed cellular serine/threonine phosphatase, that
plays important roles in the immune system and cardiac muscles. Using
global gene-profiling methods, we studied the short-time CSA effect
on the squamous cell line (SCC-015) using Affymetrix human gene chips
(Human U133, 2.0 plus chip). Multiple groups of genes were identified
to be responsive to CSA treatment, including many genes of unknown
functions. We then used reverse transcriptase–polymerase chain
reaction and immunoblot analyses to selectively confirm the results
from the chips analyses with emphasis on the regulatory molecules
important for cellular functions of apoptosis, DNA damage repair,
and cellular transformation. This global gene-profiling study indicated
that CSA not only functions as an immunosuppressant on the immune
system, but also activates/inhibits a wide array of genes important
for cell-cycle regulation, apoptosis, and oncogene/tumor-suppressor
activation. These functions of CSA on skin and mucosa systems at
the molecular level are likely important in the pathogenesis of squamous
carcinoma in transplant patients.},
issn = {1531-4995},
keywords = {Squamous cell carcinoma, transplant, cyclosporine A, chip analysis},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1097/01.mlg.0000205170.24517.28}
}
@ARTICLE{Tiwari2011,
author = {Tiwari, Krishnaraj and Paliyath, Gopinadhan},
title = {Microarray analysis of ripening-regulated gene expression and its
modulation by 1-MCP and hexanal},
journal = {Plant Physiology and Biochemistry},
year = {2011},
volume = {49},
pages = {329--340},
number = {3},
month = mar,
abstract = {Hexanal, an inhibitor of phospholipase D, has been successfully applied
for the pre- and post-harvest treatment of fruits, vegetables and
flowers. Changes in gene expression induced by hexanal and the ethylene
antagonist 1-MCP, were analyzed by microarray using TOM2 tomato oligo-array
containing approximately 12 000 unigenes. Mature green tomato fruits
were treated with 1-MCP and hexanal, RNA isolated after 10 days of
storage, and labeled cDNA synthesized for microarray analysis. A
large variation in gene expression profile was observed in 1-MCP-treated
fruits. Genes for ethylene biosynthetic pathway enzymes such as ACC-
synthase/oxidase, ethylene receptor and ethylene response factors
were heavily down-regulated in 1-MCP-treated fruits. In addition,
genes for key enzymes involved in cell wall degradation and carotenoid
development pathways were down-regulated. Hexanal treatment significantly
down-regulated ACC-synthase, and to a lesser extent, other components
of ethylene signal transduction. By contrast to MCP-treated fruits,
hexanal-treated fruits gradually ripened and showed higher levels
of lycopene and [beta]-carotene. GC-MS analysis of volatiles showed
a higher level of major volatile components in hexanal-treated fruits.
Similarities in the modulation of gene expression by hexanal and
1-MCP suggest that hexanal, in addition to being a PLD inhibitor,
may also act as a weak ethylene inhibitor.},
issn = {0981-9428},
keywords = {Ethylene antagonist, Phospholipase D, Fruit ripening, Fruit quality,
Biochemical pathways},
url = {http://www.sciencedirect.com/science/article/pii/S0981942811000088}
}
@ARTICLE{Tiwari2011a,
author = {Krishnaraj Tiwari and Gopinadhan Paliyath},
title = {Microarray analysis of ripening-regulated gene expression and its
modulation by 1-MCP and hexanal},
journal = {Plant Physiology and Biochemistry},
year = {2011},
volume = {49},
pages = {329 - 340},
number = {3},
abstract = {Hexanal, an inhibitor of phospholipase D, has been successfully applied
for the pre- and post-harvest treatment of fruits, vegetables and
flowers. Changes in gene expression induced by hexanal and the ethylene
antagonist 1-MCP, were analyzed by microarray using TOM2 tomato oligo-array
containing approximately 12Â 000 unigenes. Mature green tomato fruits
were treated with 1-MCP and hexanal, RNA isolated after 10 days of
storage, and labeled cDNA synthesized for microarray analysis. A
large variation in gene expression profile was observed in 1-MCP-treated
fruits. Genes for ethylene biosynthetic pathway enzymes such as ACC-
synthase/oxidase, ethylene receptor and ethylene response factors
were heavily down-regulated in 1-MCP-treated fruits. In addition,
genes for key enzymes involved in cell wall degradation and carotenoid
development pathways were down-regulated. Hexanal treatment significantly
down-regulated ACC-synthase, and to a lesser extent, other components
of ethylene signal transduction. By contrast to MCP-treated fruits,
hexanal-treated fruits gradually ripened and showed higher levels
of lycopene and β-carotene. GC–MS analysis of volatiles showed
a higher level of major volatile components in hexanal-treated fruits.
Similarities in the modulation of gene expression by hexanal and
1-MCP suggest that hexanal, in addition to being a PLD inhibitor,
may also act as a weak ethylene inhibitor.},
doi = {10.1016/j.plaphy.2011.01.007},
issn = {0981-9428},
keywords = {Ethylene antagonist},
url = {http://www.sciencedirect.com/science/article/pii/S0981942811000088}
}
@ARTICLE{Tiwari2008,
author = {Tiwari, Vijay K. and Cope, Leslie and McGarvey, Kelly M. and Ohm,
Joyce E. and Baylin, Stephen B.},
title = {A novel 6C assay uncovers Polycomb-mediated higher order chromatin
conformations},
journal = {Genome Res.},
year = {2008},
volume = {18},
pages = {1171--1179},
number = {7},
month = jul,
abstract = {We describe construction of a novel modification, "6C," of chromatin
looping assays that allows specific proteins that may mediate long-range
chromatin interactions to be defined. This approach combines the
standard looping approaches previously defined with an immunoprecipitation
step to investigate involvement of the specific protein. The efficacy
of this approach is demonstrated by using a Polycomb group (PcG)
protein, Enhancer of Zeste (EZH2), as an example of how our assay
might be used. EZH2, as a protein of the PcG complex, PRC2, has an
important role in the propagation of epigenetic memory through deposition
of the repressive mark, histone H3, lysine 27, tri-methylation (H3K27me3).
Using our new 6C assay, we show how EZH2 is a direct mediator of
long-range intra- and interchromosomal interactions that can regulate
transcriptional down-regulation of multiple genes by facilitating
physical proximities between distant chromatin regions, thus targeting
sites within to PcG machinery.},
url = {http://genome.cshlp.org/cgi/content/abstract/18/7/1171}
}
@ARTICLE{Tkalcevic2007,
author = {Tkalcevic, Vanesa Ivetic and Cuzic, Snjezana and Brajsa, Karmen and
Mildner, Boris and Bokulic, Ana and Situm, Kristina and Perovic,
Daniela and Glojnaric, Ines and Parnham, Michael J.},
title = {Enhancement by PL 14736 of granulation and collagen organization
in healing wounds and the potential role of egr-1 expression},
journal = {European Journal of Pharmacology},
year = {2007},
volume = {570},
pages = {212--221},
number = {1-3},
month = sep,
abstract = {Apart from becaplermin (recombinant human platelet-derived growth
factor homodimer of B chains, PDGF-BB), for the treatment of lower
extremity diabetic ulcers, few agents are available for pharmacological
stimulation of wound healing. We have compared the mechanism of action
of the potential wound healing agent, PL 14736 (G E P P P G K P A
D D A G L V), with that of PDGF-BB on granulation tissue formation
following sponge implantation in the normoglycemic rat and in healing
full-thickness excisional wounds in db/db genetically diabetic mice.
Expression of the immediate response gene, early growth response
gene-1 (egr-1) was studied in Caco-2 cells in vitro. While PDGF-BB
and PL 14736 had similar selectivity for stimulation of granulation
tissue in both sponge granuloma and in healing wounds in db/db mice,
PL 14736 was more active in stimulating early collagen organization.
It also stimulated expression of egr-1 and its repressor nerve growth
factor 1-A binding protein-2 (nab2) in non-differentiated Caco-2
cells more rapidly than PDGF-BB. EGR-1 induces cytokine and growth
factor generation and early extracellular matrix (collagen) formation,
offering an explanation for the beneficial effects of PL 14736 on
wound healing.},
issn = {0014-2999},
keywords = {Collagen, egr-1 expression, Granulation tissue, PDGF-BB, PL 14736,
Wound healing},
url = {http://www.sciencedirect.com/science/article/B6T1J-4P06CKS-1/2/f69c4bbc7bd5674a790b63e9db514a27}
}
@ARTICLE{Tochio2011,
author = {Tochio, Takumi and Tanaka, Hiroshi and Nakata, Satoru and Yoshizato,
Katsutoshi},
title = {Presence of amplifiable mRNA in acellular hair shafts: utilization
to analyze gene expression profiles of black and white hairs},
journal = {International Journal of Dermatology},
year = {2011},
volume = {50},
pages = {530--534},
number = {5},
abstract = {Abstract Background  We postulated that hair shafts preserve amplifiable
messenger RNAs (mRNAs) and that these mRNAs could be utilized to
characterize phenotypic differences in hairs at the gene expression
level.Objectives  This study aimed to prove the presence of amplifiable
mRNAs in the hair shaft and then to utilize them to characterize
black and white hairs at the gene expression level.Methods  RNAs
were extracted from black and white scalp hair shafts and amplified
by quantitative real-time polymerase chain reaction (qRT-PCR). Microarray
analysis was performed using T7 RNA polymerase-amplified mRNAs derived
from the hair shaft to examine the gene expression profiles of black
and white hairs.Results  We showed that hair shaft RNAs contained
trace amounts of mRNAs and concluded that the acellular hair shaft
contained mRNAs usable for microarray analysis. We termed the mRNA
“fossil mRNA� (fmRNA) in this study. Totals of 10 and 2% of the
detected genes were expressed at levels more than two-fold higher
in black and white hairs compared with white and black hairs, respectively.
We selected five genes and examined their expression levels in five
donors by qRT-PCR. Among them, only hypothetical protein (L1H3 region)
human was found to be expressed at 2.69 ± 1.81 (relative ratio)
in black hairs.Conclusions  We demonstrated that the scalp hair
shaft conserves fmRNAs which are probably remnants that have been
expressed during hair differentiation. Consequently, fmRNA is expected
to be a useful source of information for the study of phenotypic
changes in hairs at the molecular level.},
doi = {10.1111/j.1365-4632.2010.04749.x},
issn = {1365-4632},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-4632.2010.04749.x}
}
@ARTICLE{Toedter2011,
author = {Toedter, Gary and Li, Katherine and Marano, Colleen and Ma, Keying
and Sague, Sarah and Huang, C Chris and Song, Xiao-Yu and Rutgeerts,
Paul and Baribaud, Frederic},
title = {Gene Expression Profiling and Response Signatures Associated With
Differential Responses to Infliximab Treatment in Ulcerative Colitis},
journal = {Am J Gastroenterol},
year = {2011},
pages = {--},
month = mar,
issn = {1572-0241},
publisher = {American College of Gastroenterology},
url = {http://dx.doi.org/10.1038/ajg.2011.83}
}
@ARTICLE{Toedter2012,
author = {Toedter, Gary and Li, Katherine and Sague, Sarah and Ma, Keying and
Marano, Colleen and Macoritto, Michael and Park, Jennifer and Deehan,
Renée and Matthews, Andrea and Wu, Gary D. and Lewis, James D. and
Arijs, Ingrid and Rutgeerts, Paul and Baribaud, Frédéric},
title = {Genes associated with intestinal permeability in ulcerative colitis:
Changes in expression following infliximab therapy},
journal = {Inflammatory Bowel Diseases},
year = {2012},
pages = {n/a--n/a},
abstract = {Background:Alterations in intestinal permeability have been implicated
in ulcerative colitis (UC). Infliximab, a monoclonal anti-tumor necrosis
factor alpha (TNFα) antibody, can induce clinical response in UC.
Gene expression in colonic biopsies taken from responders and nonresponders
to infliximab can provide insight into the mechanisms of the altered
intestinal permeability at a molecular level.Methods:Colonic biopsies
(n = 18 anti-TNFα naïve UC patients; n = 8 normal controls; n =
80 Active Ulcerative Colitis Trial [ACT] 1 patients) were analyzed
for mRNA expression using gene expression microarrays. Computational
reverse causal reasoning was applied to build causal network models
of UC and response and nonresponse of UC to treatment. Quantitative
reverse-transcription polymerase chain reaction (qPCR) was used to
confirm differentially expressed genes.Results:Reverse causal reasoning
on mRNA expression data from anti-TNFα-naïve UC and normal samples
provided a mechanistic disease model of the biology of gene expression
observed in UC. mRNA expression data from the ACT 1 study enabled
construction of a mechanistic model describing the biology of nonresponders
to infliximab, including evidence for increased intestinal permeability
compared with normal and responder samples. Gene expression changes
identified as central to intestinal permeability dysregulation were
confirmed in normal, UC, and infliximab-treated patients by qPCR
analysis. Gene expression returned toward normal levels in infliximab
responders, but not in nonresponders.Conclusion:Gene expression analysis
and causal network modeling in combination showed that aberrant mRNA
expression of genes involved in intestinal epithelial permeability
for infliximab responders was restored toward levels observed in
normal samples. Infliximab nonresponders showed no equivalent restoration
in the expression of these genes. (Inflamm Bowel Dis 2012;)},
doi = {10.1002/ibd.22853},
issn = {1536-4844},
keywords = {ulcerative colitis, infliximab, tight junction, epithelial-mesenchymal
transition},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.22853}
}
@ARTICLE{Toegel2010,
author = {Toegel, S. and Pabst, M. and Wu, S.Q. and Grass, J. and Goldring,
M.B. and Chiari, C. and Kolb, A. and Altmann, F. and Viernstein,
H. and Unger, F.M.},
title = {Phenotype-related differential [alpha]-2,6- or [alpha]-2,3-sialylation
of glycoprotein N-glycans in human chondrocytes},
journal = {Osteoarthritis and Cartilage},
year = {2010},
volume = {18},
pages = {240--248},
number = {2},
month = feb,
abstract = {SummaryObjective Sialic acids frequently occur at the terminal positions
of glycoprotein N-glycans present at chondrocyte surfaces or in the
cartilage matrix. Sialic acids are transferred to glycoproteins in
either [alpha]-2,3 or [alpha]-2,6 linkage by specific sialyltransferases
(SiaTs) and can potentially affect cell functions and cell-matrix
interactions. The present study aimed to assess the relationship
between the expression of the human chondrocyte phenotype and the
sialylation of chondrocyte glycoprotein N-glycans.Methods The transcription
of 5 SiaT was quantified using real-time Reverse transcription polymerase
chain reaction (RT-PCR) assays. N-glycan analysis was performed using
LC-ESI-MS. Primary human chondrocytes were cultured in monolayer
or alginate beads and compared to the chondrocyte cell lines C-28/I2
and SW1353. In addition, effects of interleukin-1[beta] (IL-1[beta])
or tumour necrosis factor-[alpha] (TNF-[alpha]) on primary cells
were assessed.Results Primary human chondrocytes predominantly express
[alpha]-2,6-specific SiaTs and accordingly, [alpha]-2,6-linked sialic
acid residues in glycoprotein N-glycans. In contrast, the preponderance
of [alpha]-2,3-linked sialyl residues and, correspondingly, reduced
levels of [alpha]-2,6-specific SiaTs are associated with the altered
chondrocyte phenotype of C-28/I2 and SW1353 cells. Importantly, a
considerable shift towards [alpha]-2,3-linked sialic acids and [alpha]-2,3-specific
SiaT mRNA levels occurred in primary chondrocytes treated with IL-1[beta]
or tumour necrosis factor-alpha (TNF-[alpha]).Conclusion The expression
of the differentiated chondrocyte phenotype is linked to the ratio
of [alpha]-2,6- to [alpha]-2,3-linked sialic acids in chondrocyte
glycoprotein N-glycans. A shift towards altered sialylation might
contribute to impaired cell-matrix interactions in disease conditions.},
issn = {1063-4584},
keywords = {Chondrocytes, Extracellular matrix, Cell-matrix interaction, Glycoproteins,
Sialic acids, Sialyltransferases, Differentiation, Phenotype},
url = {http://www.sciencedirect.com/science/article/B6WP3-4X908XG-2/2/fc00210773265c125cdb0f3c6fab1df4}
}
@ARTICLE{Toffanin2011,
author = {Toffanin, Sara and Hoshida, Yujin and Lachenmayer, Anja and Villanueva,
Augusto and Cabellos, Laia and Minguez, Beatriz and Savic, Radoslav
and Ward, Stephen C. and Thung, Swan and Chiang, Derek Y. and Alsinet,
Clara and Tovar, Victoria and Roayaie, Sasan and Schwartz, Myron
and Bruix, Jordi and Waxman, Samuel and Friedman, Scott L. and Golub,
Todd and Mazzaferro, Vincenzo and Llovet, Josep M.},
title = {MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic
Role of miR-517a},
journal = {Gastroenterology},
year = {2011},
volume = {140},
pages = {1618--1628.e16},
number = {5},
month = may,
abstract = {Background & Aims Hepatocellular carcinoma (HCC) is a heterogeneous
tumor that develops via activation of multiple pathways and molecular
alterations. It has been a challenge to identify molecular classes
of HCC and design treatment strategies for each specific subtype.
MicroRNAs (miRNAs) are involved in HCC pathogenesis, and their expression
profiles have been used to classify cancers. We analyzed miRNA expression
in human HCC samples to identify molecular subclasses and oncogenic
miRNAs.Methods We performed miRNA profiling of 89 HCC samples using
a ligation-mediated amplification method. Subclasses were identified
by unsupervised clustering analysis. We identified molecular features
specific for each subclass using expression pattern (Affymetrix U133
2.0; Affymetrix, Santa Clara, CA), DNA change (Affymetrix STY Mapping
Array), mutation (CTNNB1), and immunohistochemical (phosphor[p]-protein
kinase B, p-insulin growth factor-IR, p-S6, p-epidermal growth factor
receptor, [beta]-catenin) analyses. The roles of selected miRNAs
were investigated in cell lines and in an orthotopic model of HCC.Results
We identified 3 main clusters of HCCs: the wingless-type MMTV integration
site (32 of 89; 36%), interferon-related (29 of 89; 33%), and proliferation
(28 of 89; 31%) subclasses. A subset of patients with tumors in the
proliferation subclass (8 of 89; 9%) overexpressed a family of poorly
characterized miRNAs from chr19q13.42. Expression of miR-517a and
miR-520c (from ch19q13.42) increased proliferation, migration, and
invasion of HCC cells in vitro. MiR-517a promoted tumorigenesis and
metastatic dissemination in vivo.Conclusions We propose miRNA-based
classification of 3 subclasses of HCC. Among the proliferation class,
miR-517a is an oncogenic miRNA that promotes tumor progression. There
is rationale for developing therapies that target miR-517a for patients
with HCC.},
issn = {0016-5085},
keywords = {Liver Cancer, Tumor Profiling, OncomiR, Oncogenesis},
url = {http://www.sciencedirect.com/science/article/pii/S0016508511001466}
}
@ARTICLE{Tohda2008,
author = {Tohda, Michihisa and Hayashi, Hisae and Sukma, Monrudee and Tanaka,
Ken},
title = {BNIP-3: A novel candidate for an intrinsic depression-related factor
found in NG108-15 cells treated with Hochu-ekki-to, a traditional
oriental medicine, or typical antidepressants},
journal = {Neuroscience Research},
year = {2008},
volume = {62},
pages = {1--8},
number = {1},
month = sep,
abstract = {Wakan-yaku is a type of Japanese and Sino traditional, systematized
medical care that has been practiced for hundreds of years. To search
for novel intrinsic factors related to the action of antidepressants,
we used Hochu-ekki-to (HET), a Wakan-yaku medicine with antidepressive
effects. First, we verified the quality of the HET by three-dimensional
high-performance liquid chromatography and a cytotoxicity check in
NG108-15 cells. We performed a DNA microarray analysis of the gene
expression in cells treated with 50 [mu]/ml HET for more than 20
days. HET enhanced the expression of 125 (2.9%) genes and decreased
the expression of 255 (6.0%) genes among the 4277 genes that were
tested. The concentration-dependent increase in the expression of
BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP-3)
mRNA was particularly remarkable. A concentration-dependent increase
in the expression of BNIP-3 mRNA was also observed when cells were
treated with imipramine, mianserin, or milnacipran. These results
suggest that BNIP-3 is a candidate for an intrinsic factor related
to antidepressive effects and that Wakan-yaku theory may be useful
for the identification of other intrinsic functional molecules.},
issn = {0168-0102},
keywords = {DNA array, Semi-quantitative RT-PCR, Depressive disorder, Sino-Japanese
traditional medicines, NG108-15 cells, BNIP-3},
url = {http://www.sciencedirect.com/science/article/B6T0H-4SMWF6G-1/2/4c3a6c6784c5f75b051c9cd005b6f7e3}
}
@ARTICLE{Toillon2007,
author = {Toillon, Robert-Alain and Magné, Nicolas and Laïos, Ioanna and Castadot,
Pierre and Kinnaert, Eric and Van Houtte, Paul and Desmedt, Christine
and Leclercq, Guy and Lacroix, Marc},
title = {Estrogens decrease [gamma]-ray-induced senescence and maintain cell
cycle progression in breast cancer cells independently of p53},
journal = {International Journal of Radiation Oncology*Biology*Physics},
year = {2007},
volume = {67},
pages = {1187--1200},
number = {4},
month = mar,
abstract = {Purpose: Sequential administration of radiotherapy and endocrine therapy
is considered to be a standard adjuvant treatment of breast cancer.
Recent clinical reports suggest that radiotherapy could be more efficient
in association with endocrine therapy. The aim of this study was
to evaluate the estrogen effects on irradiated breast cancer cells
(IR-cells). Methods and Materials: Using functional genomic analysis,
we examined the effects of 17-[beta]-estradiol (E2, a natural estrogen)
on MCF-7 breast cancer cells. Results: Our results showed that E2
sustained the growth of IR-cells. Specifically, estrogens prevented
cell cycle blockade induced by [gamma]-rays, and no modification
of apoptotic rate was detected. In IR-cells we observed the induction
of genes involved in premature senescence and cell cycle progression
and investigated the effects of E2 on the p53/p21waf1/cip1/Rb pathways.
We found that E2 did not affect p53 activation but it decreased cyclin
E binding to p21waf1/cip1 and sustained downstream Rb hyperphosphorylation
by functional inactivation of p21waf1/cip1. We suggest that Rb inactivation
could decrease senescence and allow cell cycle progression in IR-cells.
Conclusion: These results may help to elucidate the molecular mechanism
underlying the maintenance of breast cancer cell growth by E2 after
irradiation-induced damage. They also offer clinicians a rational
basis for the sequential administration of ionizing radiation and
endocrine therapies.},
issn = {0360-3016},
keywords = {Estrogen, Senescence, Breast cancer, Radiation, p53, p21waf1/cip1,
DNA damage, Rb, Cyclin},
url = {http://www.sciencedirect.com/science/article/B6T7X-4N5631F-C/2/a539aae0c42474fbd3b9c2443008b0a7}
}
@ARTICLE{Tojo2009,
author = {Tojo, Yosuke and Hamase, Kenji and Konno, Ryuichi and Koyanagi, Satoru
and Ohdo, Shigehiro and Zaitsu, Kiyoshi},
title = {Simple and rapid genotyping of D-amino acid oxidase gene recognizing
a crucial variant in the ddY strain using microchip electrophoresis},
journal = {J. Sep. Science},
year = {2009},
volume = {32},
pages = {430--436},
number = {3},
abstract = {Abstract 10.1002/jssc.200800587.abs A rapid genotyping method of D-amino
acid oxidase (DAO), an enzyme that catalyzes the oxidative degradation
of most of the D-amino acids in mammals, has been established. This
method employs a one-step PCR, restriction enzyme digestion and rapid
microchip electrophoresis (MCE), and the DAO genotype of the living
individual mice was definitely determined within a day by clearly
separating the 95 and 107 bp Hpa II digested DNA fragments. For verification
of the method, the DAO activity in the kidney of individual mice
was also determined, and the obtained values completely matched the
estimated genotypes (DAO+/+, DAO+/–, and DAO–/–). The intrinsic
amounts of D-Pro in the serum and kidney of mice with three DAO genotypes
were compared for the first time, and demonstrated that the D-amino
acid amounts in the DAO+/+ mice (1.93 ± 0.66 nmol/mL serum, not
detectable in the kidney) and DAO+/– mice (1.50 ± 0.24 nmol/mL
serum, not detectable in the kidney) were almost the same. The present
method should be a powerful tool to establish various pathologic-model
animals under the complete care of their intrinsic DAO activity,
which are useful for the screening of D-amino acids having physiological
activity and/or diagnostic values.},
issn = {1615-9314},
keywords = {D-Amino acid, D-Amino acid oxidase, Genotyping, Microchip electrophoresis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/jssc.200800587}
}
@ARTICLE{Tokarska-Schlattner2010,
author = {Tokarska-Schlattner, Malgorzata and Lucchinetti, Eliana and Zaugg,
Michael and Kay, Laurence and Gratia, Severine and Guzun, Rita and
Saks, Valdur and Schlattner, Uwe},
title = {Early effects of doxorubicin in perfused heart: transcriptional profiling
reveals inhibition of cellular stress response genes},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2010},
volume = {298},
pages = {R1075--1088},
number = {4},
month = apr,
abstract = {Doxorubicin (DXR) belongs to the most efficient anticancer drugs.
However, its clinical application is limited by the risk of severe
cardiac-specific toxicity, for which an efficient treatment is missing.
Underlying molecular mechanisms are not sufficiently understood so
far, but nonbiased, systemic approaches can yield new clues to develop
targeted therapies. Here, we applied a genome-wide transcriptome
analysis to determine the early cardiac response to DXR in a model
characterized earlier, that is, rat heart perfusion with 2 {micro}M
DXR, leading to only mild cardiac dysfunction. Single-gene and gene
set enrichment analysis of DNA microarrays yielded robust data on
cardiac transcriptional reprogramming, including novel DXR-responsive
pathways. Main characteristics of transcriptional reprogramming were
1) selective upregulation of individual genes or gene sets together
with widespread downregulation of gene expression; 2) repression
of numerous transcripts involved in cardiac stress response and stress
signaling; 3) modulation of genes with cardiac remodeling capacity;
4) upregulation of "energy-related" pathways; and 5) similarities
to the transcriptional response of cancer cells. Some early responses
like the induction of glycolytic and Krebs cycle genes may have compensatory
function. Only minor changes in the cardiac energy status or the
respiratory activity of permeabilized cardiac fibers have been observed.
Other responses potentially contribute to acute and also chronic
toxicity, in particular, those in stress-responsive and cardiac remodeling
transcripts. We propose that a blunted response to stress and reduced
"danger signaling" is a prime component of toxic DXR action and can
drive cardiac cells into pathology.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/298/4/R1075}
}
@ARTICLE{Toki2005,
author = {Toki, Tsutomu and Katsuoka, Fumiki and Kanezaki, Rika and Xu, Gang
and Kurotaki, Hidekachi and Sun, Jiying and Kamio, Takuya and Watanabe,
Seiji and Tandai, Satoru and Terui, Kiminori and Yagihashi, Soroku
and Komatsu, Norio and Igarashi, Kazuhiko and Yamamoto, Masayuki
and Ito, Etsuro},
title = {Transgenic expression of BACH1 transcription factor results in megakaryocytic
impairment},
journal = {Blood},
year = {2005},
volume = {105},
pages = {3100--3108},
number = {8},
month = apr,
abstract = {Both nuclear factor erythroid 2 45 kDa subunit (p45) and BTB and CNC
homolog 1 (Bach) transcription factors can form dimers with one of
the small Maf proteins, and these heterodimers bind to the musculoaponeurotic
fibrosarcoma oncogene (Maf) recognition element (MARE). MARE is known
to act as a critical cis-regulatory element of erythroid and megakaryocytic
genes. Although detailed analyses of p45-null mutant mice and small
maf compound mutant mice revealed that these factors are both critical
for platelet production, the functional contributions of Bach1 and
the relationship or redundancy between Bach1 and p45 in megakaryocytes
remain to be clarified. To address these issues, we generated transgenic
lines of mice bearing human BACH1 cDNA under the control of the GATA-1
locus hematopoietic regulatory domain. The transgenic mouse lines
showed significant thrombocytopenia associated with impaired maturation
of the megakaryocytes, and they developed myelofibrosis. The megakaryocytes
in the transgenic mice exhibited reduced proplatelet formation, and
the modal ploidy class of megakaryocytes was 2N, indicating the impairment
of endomitosis. Transcription of the p45 target genes was down-regulated
and we indeed found that BACH1 binds to the thromboxane synthase
gene, one of the target genes for p45 in megakaryocytes. These findings
thus provide evidence that BACH1 acts as a transcriptional repressor
in the regulation of MARE-dependent genes in megakaryocytes.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/105/8/3100}
}
@ARTICLE{Tokunaga2007,
author = {Tokunaga, Takaaki and Esaka, Muneharu},
title = {Induction of a Novel XIP-Type Xylanase Inhibitor by External Ascorbic
Acid Treatment and Differential Expression of XIP-Family Genes in
Rice},
journal = {Plant Cell Physiol.},
year = {2007},
volume = {48},
pages = {700--714},
number = {5},
month = may,
abstract = {Rice microarray analysis showed that a number of stress-related genes
are induced by external addition of L-ascorbic acid (AsA). The gene
designated as AK073843 which is homologous to class [SHcy] chitinase
was found to exhibit the highest induction among these genes. However,
its crucial residues within the chitinase active site are substituted
with other residues, suggesting that the protein has no chitinase
activity. The recombinant protein which is encoded by the AK073843
gene produced in Escherichia coli has xylanase inhibitor activity,
indicating that the gene encodes a novel rice XIP-type xylanase inhibitor
protein (OsXIP). The expression of OsXIP was enhanced not only by
exogenous AsA treatment but also by various stresses such as citrate
and sodium chloride treatments, and wounding; however, it was not
influenced by increasing endogenous AsA content. External AsA treatment
caused a significant increase in electrolyte leakage from rice root.
These results suggested that OsXIP was induced by stress which is
caused by external AsA treatment. Rice XIP-family genes, OsXIP, riceXIP
and RIXI, showed differential organ-specific expression. Also, these
genes were differentially induced by stress and stress-related phytohormones.
The transcripts of OsXIP and riceXIP were undetectable under normal
conditions, and were drastically induced by wounding and methyl jasmonate
(MeJA) treatment in the root. RIXI was constitutively expressed in
the shoot but not induced by wounding and stress-related phytohormones.
Thus, XIP-type xylanase inhibitors were suggested to be specialized
in their function and involved in defense mechanisms in rice.},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/48/5/700}
}
@ARTICLE{Tokuyama2008,
author = {Tokuyama, Y. and Reddy, A.P. and Bethea, C.L.},
title = {Neuroprotective actions of ovarian hormones without insult in the
raphe region of rhesus macaques},
journal = {Neuroscience},
year = {2008},
volume = {154},
pages = {720--731},
number = {2},
month = jun,
abstract = {Using a nonhuman primate model of surgical menopause, our laboratory
has shown that ovarian hormone treatment (HT) improves 5-HT neural
function in the dorsal raphe nucleus (DRN). We further hypothesize
that HT may increase 5-HT neuronal resilience. Recent data from microarray
analysis indicated that HT regulates gene expression in pathways
that lead to apoptosis. In this study, we questioned whether HT alters
protein expression in caspase-dependent and independent pathways.
Ovariectomized monkeys received Silastic implants containing placebo
(empty), estrogen (E) or E+ progesterone (P). A small block of the
midbrain containing the DRN was dissected and subjected to subcellular
fractionation, yielding cytosolic, nuclear and mitochondrial fractions
(n=4/group). The pro-apoptotic protein, c-jun n-terminal kinase (JNK1)
and its phosphorylation were decreased by E+P treatment in the cytosolic
fraction. Downstream of JNK are proteins in the caspase-dependent
and -independent pathways. First, in the caspase-dependent pathway,
cytoplasmic and mitochondrial fractions were immunoblotted for Bcl-2
family members, cytochrome c, Apaf1 and XIAP. However, the expression
of these proteins did not differ among treatments. Pro-caspase 3
was decreased by E+P, but there was no evidence of active caspase
in any group. Then, we examined the involvement of a protein in the
caspase-independent pathway, called apoptosis-inducing factor (AIF).
AIF mRNA (n=3/group) and AIF mitochondrial protein tended to decrease
with hormone treatment. However, AIF protein in the nuclear fraction
in E+P treated monkeys was significantly reduced. This indicates
that HT is reducing the translocation of AIF from mitochondria to
nucleus, thus inhibiting AIF-mediated apoptosis. AIF was immunocytochemically
localized to large 5-HT-like neurons of the dorsal raphe. These data
suggest that in the absence of global trauma or ischemia, HT may
act through the caspase-independent pathway to promote neuroprotection
in the 5-HT system.},
issn = {0306-4522},
keywords = {estrogen, 5-HT, apoptosis, neuroprotection, AIF, JNK},
url = {http://www.sciencedirect.com/science/article/B6T0F-4S6G93F-1/2/a642575b2c0e56b8422ba787e2a689e4}
}
@ARTICLE{Tolley2011,
author = {Tolley, Ben J. and Woodfield, Helen and Wanchana, Samart and Bruskiewich,
Richard and Hibberd, Julian M.},
title = {Light-regulated and cell-specific methylation of the maize PEPC promoter},
journal = {J. Exp. Bot.},
year = {2011},
pages = {err367},
abstract = {The molecular mechanisms governing PEPC expression in maize remain
to be fully defined. Differential methylation of a region in the
PEPC promoter has been shown to correlate with transcript accumulation,
however, to date, investigations into the role of DNA methylation
in maize PEPC expression have relied on the use of methylation-sensitive
restriction enzymes. Bisulphite sequencing was used here to provide
a single-base resolution methylation map of the maize PEPC promoter.
It is shown that four cytosine residues in the PEPC promoter are
heavily methylated in maize root tissue. In leaves, de-methylation
of these cytosines is dependent on illumination and is coincident
with elevated PEPC expression. Furthermore, light-regulated de-methylation
of these cytosines occurs only in mesophyll cells. No methylation
was discovered in the 0.6 kb promoter required for mesophyll-specific
expression indicating that cytosine methylation is not required to
direct the cell-specificity of PEPC expression. This raises interesting
questions regarding the function of the cell-specific cytosine de-methylation
observed in the upstream region of the PEPC promoter.},
doi = {10.1093/jxb/err367},
eprint = {http://jxb.oxfordjournals.org/cgi/reprint/err367v1.pdf},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/err367v1}
}
@ARTICLE{Toloubeydokhti2008,
author = {Toloubeydokhti, Tannaz and Qun Pan and Xiaoping Luo and Bukulmez,
Orhan and Chegini, Nasser},
title = {The Expression and Ovarian Steroid Regulation of Endometrial Micro-RNAs},
journal = {Reproductive Sciences},
year = {2008},
volume = {15},
pages = {993--1001},
number = {10},
month = dec,
abstract = {MicroRNAs (miRNAs) which regulate gene expression stability displayed
an aberrant expression profile in ectopic endometrium (ECE) as compared
to eutopic (EUE) and normal endometrium (NE). We assessed the expression
of miR-17-5p, miR-23a, miR-23b and miR-542-3p, their predicted target
genes, steroidogenic acute regulatory protein, aromatase and cyclooxygenase-2,
and influence of ovarian steroids on their expression in endometrial
stromal (ESC) and glandular epithelial cells (GEC). The results indicated
a lower expression of miR-23b and miR-542-3p and higher level of
miR-17-5p in paired ECE and EUE as compared with NE. These levels
were elevated and inversely correlated with the level of expression
of their respective target genes in ECE. The expression of these
miRNAs and genes was differentially regulated by 17{beta}- estradiol,
medroxyprogesterone acetate, ICI-182780 and RU-486, or their respective
combinations in ESC and GEC. We concluded that altered expression
of specific miRNAs in ECE, affecting the stability of their target
genes expression, has direct implications in pathogenesis of endometriosis.},
url = {http://rsx.sagepub.com/cgi/content/abstract/15/10/993}
}
@ARTICLE{Tom-KunYamagishi2011,
author = {Tom-Kun Yamagishi, Valerie and Torneck, Calvin D. and Friedman, Shimon
and Huang, George T.-J. and Glogauer, Michael},
title = {Blockade of TLR2 Inhibits Porphyromonas gingivalis Suppression of
Mineralized Matrix Formation by Human Dental Pulp Stem Cells},
journal = {Journal of Endodontics},
year = {2011},
volume = {37},
pages = {812--818},
number = {6},
month = jun,
abstract = {Introduction Human dental pulp stem/progenitor cells (hDPSC) can differentiate
into odontoblast-like cells and express dentin sialophosphoprotein
(DSPP) and osteocalcin (OCN); thus, they may be used to regenerate
dentin. However, residual bacterial components in the root canal
may suppress this activity.Purpose This study investigated the effect
of a Porphyromonas gingivalis component on the expression of DSPP
and OCN by stimulated hDPSCs and the influence of blockade of TLR2-mediated
P. gingivalis host recognition.Methods Stimulated hDPSCs were exposed
to varying concentrations of P. gingivalis lipopolysaccharide (LPS),
and the expression of DSPP and OCN was measured. Similar groups of
stimulated hDPSCs were exposed to TLR2 blocking agents before exposure
to LPS.Results hDPSCs exposed to 5, 10, and 20 [mu]g/mL LPS exhibited
a dose-dependent reduction in the expression of DSPP (3.19 ± 0.18,
2.60 ± 0.49, and 1.15 ± 0.29, respectively) and OCN (3.51 ± 1.18,
2.60 ± 0.67 and 1.66 ± 0.89, respectively). The expression of DSPP
and OCN after exposure to 20 [mu]g/mL of LPS was significantly lower
than measured for unexposed stimulated cells (analysis of variance
and post hoc Tukey test, P < .05). The blockade of TLR2 using an
extra- and intracellular agent affected DSPP (4.67 ± 0.97 and 5.29
± 1.66, respectively) and OCN (5.25 ± 1.69 and 5.82 ± 2.38, respectively)
expression at levels comparable to stimulated cells unexposed to
20 [mu]g/mL LPS (6.32 ± 2.47 and 4.70 ± 1.60 for DSPP and OCN, respectively).Conclusions
The suppressing effect of P. gingivalis on mineralized matrix formation
by hDPSCs is confirmed, and this suppression can be moderated by
TLR2 blockade.},
issn = {0099-2399},
keywords = {Dental pulp stem cells, dentin sialophosphoprotein, osteocalcin, Porphyromonas
gingivalis, TLR2},
url = {http://www.sciencedirect.com/science/article/pii/S0099239911003712}
}
@ARTICLE{Tomasson2008,
author = {Tomasson, Michael H. and Xiang, Zhifu and Walgren, Richard and Zhao,
Yu and Kasai, Yumi and Miner, Tracie and Ries, Rhonda E. and Lubman,
Olga and Fremont, Daved H. and McLellan, Michael D. and Payton, Jacqueline
E. and Westervelt, Peter and DiPersio, John F. and Link, Daniel C.
and Walter, Matthew J. and Graubert, Timothy A. and Watson, Mark
and Baty, Jack and Heath, Sharon and Shannon, William D. and Nagarajan,
Rakesh and Bloomfield, Clara D. and Mardis, Elaine R. and Wilson,
Richard K. and Ley, Timothy J.},
title = {Somatic mutations and germline sequence variants in the expressed
tyrosine kinase genes of patients with de novo acute myeloid leukemia},
journal = {Blood},
year = {2008},
volume = {111},
pages = {4797--4808},
number = {9},
month = may,
abstract = {Activating mutations in tyrosine kinase (TK) genes (eg, FLT3 and KIT)
are found in more than 30% of patients with de novo acute myeloid
leukemia (AML); many groups have speculated that mutations in other
TK genes may be present in the remaining 70%. We performed high-throughput
resequencing of the kinase domains of 26 TK genes (11 receptor TK;
15 cytoplasmic TK) expressed in most AML patients using genomic DNA
from the bone marrow (tumor) and matched skin biopsy samples ("germline")
from 94 patients with de novo AML; sequence variants were validated
in an additional 94 AML tumor samples (14.3 million base pairs of
sequence were obtained and analyzed). We identified known somatic
mutations in FLT3, KIT, and JAK2 TK genes at the expected frequencies
and found 4 novel somatic mutations, JAK1V623A, JAK1T478S, DDR1A803V,
and NTRK1S677N, once each in 4 respective patients of 188 tested.
We also identified novel germline sequence changes encoding amino
acid substitutions (ie, nonsynonymous changes) in 14 TK genes, including
TYK2, which had the largest number of nonsynonymous sequence variants
(11 total detected). Additional studies will be required to define
the roles that these somatic and germline TK gene variants play in
AML pathogenesis.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/9/4797}
}
@ARTICLE{Tombol2009,
author = {Tombol, Zsofia and Szabo, Peter M and Molnar, Viktor and Wiener,
Zoltan and Tolgyesi, Gergely and Horanyi, Janos and Riesz, Peter
and Reismann, Peter and Patocs, Attila and Liko, Istvan and Gaillard,
Rolf-Christian and Falus, Andras and Racz, Karoly and Igaz, Peter},
title = {Integrative molecular bioinformatics study of human adrenocortical
tumors: microRNA, tissue-specific target prediction, and pathway
analysis},
journal = {Endocr. Relat. Cancer},
year = {2009},
volume = {16},
pages = {895--906},
number = {3},
month = sep,
abstract = {MicroRNAs (miRs) are involved in the pathogenesis of several neoplasms;
however, there are no data on their expression patterns and possible
roles in adrenocortical tumors. Our objective was to study adrenocortical
tumors by an integrative bioinformatics analysis involving miR and
transcriptomics profiling, pathway analysis, and a novel, tissue-specific
miR target prediction approach. Thirty-six tissue samples including
normal adrenocortical tissues, benign adenomas, and adrenocortical
carcinomas (ACC) were studied by simultaneous miR and mRNA profiling.
A novel data-processing software was used to identify all predicted
miR-mRNA interactions retrieved from PicTar, TargetScan, and miRBase.
Tissue-specific target prediction was achieved by filtering out mRNAs
with undetectable expression and searching for mRNA targets with
inverse expression alterations as their regulatory miRs. Target sets
and significant microarray data were subjected to Ingenuity Pathway
Analysis. Six miRs with significantly different expression were found.
miR-184 and miR-503 showed significantly higher, whereas miR-511
and miR-214 showed significantly lower expression in ACCs than in
other groups. Expression of miR-210 was significantly lower in cortisol-secreting
adenomas than in ACCs. By calculating the difference between dCTmiR-511
and dCTmiR-503 (delta cycle threshold), ACCs could be distinguished
from benign adenomas with high sensitivity and specificity. Pathway
analysis revealed the possible involvement of G2/M checkpoint damage
in ACC pathogenesis. To our knowledge, this is the first report describing
miR expression patterns and pathway analysis in sporadic adrenocortical
tumors. miR biomarkers may be helpful for the diagnosis of adrenocortical
malignancy. This tissue-specific target prediction approach may be
used in other tumors too.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/16/3/895}
}
@ARTICLE{Tombolan2011,
author = {Lucia Tombolan and Francesca Orso and Vincenza Guzzardo and Silvia
Casara and Angelica Zin and Massimo Bonora and Chiara Romualdi and
Carlotta Giorgi and Gianni Bisogno and Rita Alaggio and Paolo Pinton
and Cristiano De Pittà and Daniela Taverna and Angelo Rosolen and
Gerolamo Lanfranchi},
title = {High IGFBP2 Expression Correlates with Tumor Severity in Pediatric
Rhabdomyosarcoma},
journal = {The American Journal of Pathology},
year = {2011},
volume = {179},
pages = {2611 - 2624},
number = {5},
abstract = {Rhabdomyosarcoma (RMS) is the most common childhood sarcoma and is
identified as either the embryonal or alveolar (ARMS) subtype. In
approximately 75% of cases, ARMSs are characterized by specific chromosomal
translocations that involve PAX and FKHR genes. ARMS gene expression
signatures vary, depending on the presence or absence of the translocations.
Insulin-like growth factor–binding protein 2 (IGFBP2) is strongly
overexpressed in translocation-negative RMS. Because IGFBP2 is associated
with tumorigenesis, we investigated its functional role in RMS. An
analysis of IGFBP2 distribution in RMS cell lines revealed a strong
accumulation in the Golgi complex, in which morphological characteristics
appeared peculiarly modified. After silencing IGFBP2 expression,
our microarray analysis revealed mostly cell cycle and actin cytoskeleton
gene modulations. In parallel, IGFBP2-silenced cells showed reduced
cell cycle and rates of invasion and decreased seeding in the lungs
after tail vein injections in immunodeficient mice. An analysis of
IGFBP2 mRNA and protein localization in human tumors showed abnormal
protein accumulation in the Golgi complex, mostly in PAX/FKHR-negative
RMS. Moreover, an analysis of patients with RMS revealed the presence
of conspicuous circulating levels of IGFBP2 proteins in children
with highly aggressive RMS tumors. Taken together, our data provide
evidence that IGFBP2 contributes to tumor progression and that it
could be used as a marker to better classify clinical and biological
risks in RMS.},
doi = {10.1016/j.ajpath.2011.07.018},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011007371}
}
@ARTICLE{Tominaga2010,
author = {Tominaga, Ei-ichiro and Tsuda, Hiroshi and Arao, Tokuzo and Nishimura,
Sadako and Takano, Masashi and Kataoka, Fumio and Nomura, Hiroyuki
and Hirasawa, Akira and Aoki, Daisuke and Nishio, Kazuto},
title = {Amplification of GNAS may be an independent, qualitative, and reproducible
biomarker to predict progression-free survival in epithelial ovarian
cancer},
journal = {Gynecologic Oncology},
year = {2010},
volume = {118},
pages = {160--166},
number = {2},
month = aug,
abstract = {Objectives The purpose of this study was to identify genes that predict
progression-free survival (PFS) in advanced epithelial ovarian cancer
(aEOC) receiving standard therapy.Methods We performed microarray
analysis on laser microdissected aEOC cells. All cases received staging
laparotomy and adjuvant chemotherapy (carboplatin + paclitaxel) as
primary therapy.Results Microarray analysis identified 50 genes differentially
expressed between tumors of patients with no evidence of disease
(NED) or evidence of disease (ED) (p < 0.001). Six genes (13%) were
located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected
gene set/analyzed gene set in chromosomes 8 and 20 are significantly
higher than that in other chromosome regions (6/606 vs. 32/13656,
p = 0.01) and (12/383 vs. 32/13656, p = 1.3 × 10-16). We speculate
that the abnormal chromosomal distribution is due to genomic alteration
and that these genes may play an important role in aEOC and choose
GNAS (GNAS complex locus, NM_000516) on 20q13 based on the p value
and fold change. Genomic PCR of aEOC cells also showed that amplification
of GNAS was significantly correlated with unfavorable PFS (p = 0.011).
Real-time quantitative RT-PCR analysis of independent samples revealed
that high mRNA expression levels of the GNAS genes, located at chromosome
20q13, was significantly unfavorable indicators of progression-free
survival (PFS). Finally, GNAS amplification was an independent prognostic
factor for PFS.Conclusions Our results suggest that GNAS gene amplification
may be an independent, qualitative, and reproducible biomarker of
PFS in aEOC.},
issn = {0090-8258},
keywords = {Ovarian cancer, Prognosis, Amplification, Biomarker, Carboplatin,
Paclitexal},
url = {http://www.sciencedirect.com/science/article/B6WG6-505G2BV-1/2/bbb28e63a7220467720215cdcb03f658}
}
@ARTICLE{Tominaga2005,
author = {Tominaga, Yuichi and Tamguney, Tanja and Kolesnichenko, Marina and
Bilanges, Benoit and Stokoe, David},
title = {Translational Deregulation in PDK-1-/- Embryonic Stem Cells},
journal = {Mol. Cell. Biol.},
year = {2005},
volume = {25},
pages = {8465--8475},
number = {19},
month = oct,
abstract = {PDK-1 is a protein kinase that is critical for the activation of many
downstream protein kinases in the AGC superfamily, through phosphorylation
of the activation loop site on these substrates. Cells lacking PDK-1
show decreased activity of these protein kinases, including protein
kinase B (PKB) and p70S6K, whereas mTOR activity remains largely
unaffected. Here we show, by assessing both association of cellular
RNAs with polysomes and by metabolic labeling, that PDK-1-/- embryonic
stem (ES) cells exhibit defects in mRNA translation. We identify
which mRNAs are most dramatically translationally regulated in cells
lacking PDK-1 expression by performing microarray analysis of total
and polysomal RNA in these cells. In addition to the decreased translation
of many RNAs, a smaller number of RNAs show increased association
with polyribosomes in PDK-1-/- ES cells relative to PDK-1+/+ ES cells.
We show that PKB activity is a critical downstream component of PDK-1
in mediating translation of cystatin C, RANKL, and Rab11a, whereas
mTOR activity is less important for effective translation of these
targets.},
url = {http://mcb.asm.org/cgi/content/abstract/25/19/8465}
}
@ARTICLE{Tomita2004,
author = {Tomita, Akihiro and Buchholz, Daniel R. and Shi, Yun-Bo},
title = {Recruitment of N-CoR/SMRT-TBLR1 Corepressor Complex by Unliganded
Thyroid Hormone Receptor for Gene Repression during Frog Development},
journal = {Mol. Cell. Biol.},
year = {2004},
volume = {24},
pages = {3337--3346},
number = {8},
month = apr,
abstract = {The corepressors N-CoR (nuclear receptor corepressor) and SMRT (silencing
mediator for retinoid and thyroid hormone receptors) interact with
unliganded nuclear hormone receptors, including thyroid hormone (T3)
receptor (TR). Several N-CoR/SMRT complexes containing histone deacetylases
have been purified. The best studied among them are N-CoR/SMRT complexes
containing TBL1 (transducin beta-like protein 1) or TBLR1 (TBL1-related
protein). Despite extensive studies of these complexes, there has
been no direct in vivo evidence for the interaction of TBL1 or TBLR1
with TR or the possible involvement of such complexes in gene repression
by any nuclear receptors in any animals. Here, we used the frog oocyte
system to demonstrate that unliganded TR interacts with TBLR1 and
recruits TBLR1 to its chromatinized target promoter in vivo, accompanied
by histone deacetylation and gene repression. We further provide
evidence to show that the recruitment of TBLR1 or related proteins
is important for repression by unliganded TR. To investigate the
potential role for TBLR1 complexes during vertebrate development,
we made use of T3-dependent amphibian metamorphosis as a model. We
found that TBLR1, SMRT, and N-CoR are recruited to T3-inducible promoters
in premetamorphic tadpoles and are released upon T3 treatment, which
induces metamorphosis. More importantly, we demonstrate that the
dissociation of N-CoR/SMRT-TBLR1 complexes from endogenous TR target
promoters is correlated with the activation of these genes during
spontaneous metamorphosis. Taken together, our studies provide in
vivo evidence for targeted recruitment of N-CoR/SMRT-TBLR1 complexes
by unliganded TR in transcriptional repression during vertebrate
development.},
url = {http://mcb.asm.org/cgi/content/abstract/24/8/3337}
}
@ARTICLE{Tomita2004a,
author = {Tomita, Hiroaki and Vawter, Marquis P. and Walsh, David M. and Evans,
Simon J. and Choudary, Prabhakara V. and Li, Jun and Overman, Kevin
M. and Atz, Mary E. and Myers, Richard M. and Jones, Edward G. and
Watson, Stanley J. and Akil, Huda and Bunney, William E.},
title = {Effect of agonal and postmortem factors on gene expression profile:
quality control in microarray analyses of postmortem human brain},
journal = {Biological Psychiatry},
year = {2004},
volume = {55},
pages = {346--352},
number = {4},
month = feb,
abstract = {There are major concerns that specific agonal conditions, including
coma and hypoxia, might affect ribonucleic acid (RNA) integrity in
postmortem brain studies. We report that agonal factors significantly
affect RNA integrity and have a major impact on gene expression profiles
in microarrays. In contrast to agonal factors, gender, age, and postmortem
factors have less effect on gene expression profiles. The Average
Correlation Index is proposed as a method for evaluating RNA integrity
on the basis of similarity of microarray profiles. Reducing the variance
due to agonal factors is critical in investigating small but validated
gene expression differences in messenger RNA levels between psychiatric
patients and control subjects.},
issn = {0006-3223},
keywords = {Adenine-Uracil-rich elements, bipolar disorder, freezer interval,
iron-responsive element, major depressive disorder, postmortem interval},
url = {http://www.sciencedirect.com/science/article/B6T4S-4BGHM5N-2/2/2ed2822d6a157757d3482c3489daa61e}
}
@ARTICLE{Tomlinson2008,
author = {Tomlinson, Chris and Thimma, Manjula and Alexandrakis, Stelios and
Castillo, Tito and Dennis, Jayne and Brooks, Anthony and Bradley,
Thomas and Turnbull, Carly and Blaveri, Ekaterini and Barton, Geraint
and Chiba, Norie and Maratou, Klio and Soutter, Pat and Aitman, Tim
and Game, Laurence},
title = {MiMiR – an integrated platform for microarray data sharing, mining
and analysis},
journal = {BMC Bioinformatics},
year = {2008},
volume = {9},
pages = {379},
number = {1},
abstract = {BACKGROUND:Despite considerable efforts within the microarray community
for standardising data format, content and description, microarray
technologies present major challenges in managing, sharing, analysing
and re-using the large amount of data generated locally or internationally.
Additionally, it is recognised that inconsistent and low quality
experimental annotation in public data repositories significantly
compromises the re-use of microarray data for meta-analysis. MiMiR,
the Microarray data Mining Resource was designed to tackle some of
these limitations and challenges. Here we present new software components
and enhancements to the original infrastructure that increase accessibility,
utility and opportunities for large scale mining of experimental
and clinical data.RESULTS:A user friendly Online Annotation Tool
allows researchers to submit detailed experimental information via
the web at the time of data generation rather than at the time of
publication. This ensures the easy access and high accuracy of meta-data
collected. Experiments are programmatically built in the MiMiR database
from the submitted information and details are systematically curated
and further annotated by a team of trained annotators using a new
Curation and Annotation Tool. Clinical information can be annotated
and coded with a clinical Data Mapping Tool within an appropriate
ethical framework. Users can visualise experimental annotation, assess
data quality, download and share data via a web-based experiment
browser called MiMiR Online. All requests to access data in MiMiR
are routed through a sophisticated middleware security layer thereby
allowing secure data access and sharing amongst MiMiR registered
users prior to publication. Data in MiMiR can be mined and analysed
using the integrated EMAAS open source analysis web portal or via
export of data and meta-data into Rosetta Resolver data analysis
package.CONCLUSION:The new MiMiR suite of software enables systematic
and effective capture of extensive experimental and clinical information
with the highest MIAME score, and secure data sharing prior to publication.
MiMiR currently contains more than 150 experiments corresponding
to over 3000 hybridisations and supports the Microarray Centre's
large microarray user community and two international consortia.
The MiMiR flexible and scalable hardware and software architecture
enables secure warehousing of thousands of datasets, including clinical
studies, from microarray and potentially other -omics technologies.},
doi = {10.1186/1471-2105-9-379},
issn = {1471-2105},
pubmedid = {18801157},
url = {http://www.biomedcentral.com/1471-2105/9/379}
}
@ARTICLE{Tomokuni2011,
author = {Akira Tomokuni and Hidetoshi Eguchi and Yoshito Tomimaru and Hiroshi
Wada and Koichi Kawamoto and Shogo Kobayashi and Shigeru Marubashi
and Masahiro Tanemura and Hiroaki Nagano and Masaki Mori and Yuichiro
Doki},
title = {miR-146a suppresses the sensitivity to interferon-α in hepatocellular
carcinoma cells},
journal = {Biochemical and Biophysical Research Communications},
year = {2011},
volume = {414},
pages = {675 - 680},
number = {4},
abstract = {Background Interferon-based (IFN-based) therapy is effective in the
treatment of advanced hepatocellular carcinoma (HCC). However, the
issue of resistance to this therapy remains to be solved. The aim
of this study was to identify microRNAs (miRNAs) that govern the
sensitivity to IFN-α in HCC cells. Methods miRNA microarray analysis
using IFN-α-resistant clones of PLC/PRF/5 (PLC-Rs) and their parental
cells (PLC-P) was conducted. Changes in the anti-cancer effects of
IFN-α were studied after gain-of-function and loss-of-function of
the candidate miRNA. Results miR-146a expression was significantly
higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity
to IFN-α through the suppression of apoptosis. Further experiments
showed that miR-146a-related resistance to IFN-α was mediated through
SMAD4. Conclusions The results indicated that miR-146a regulated
the sensitivity of HCC cells to the cytotoxic effects of IFN-α through
SMAD4, suggesting that this miRNA could be suitable for prediction
of the clinical response and potential therapeutic target in HCC
patients on IFN-based therapy.},
doi = {10.1016/j.bbrc.2011.09.124},
issn = {0006-291X},
keywords = {MicroRNA},
url = {http://www.sciencedirect.com/science/article/pii/S0006291X11017396}
}
@ARTICLE{Tomsic2010,
author = {Tomsic, Jerneja and Guda, Kishore and Liyanarachchi, Sandya and Hampel,
Heather and Natale, Leanna and Markowitz, Sanford D. and Tanner,
Stephan M. and de la Chapelle, Albert},
title = {Allele-specific expression of TGFBR1 in colon cancer patients},
journal = {Carcinogenesis},
year = {2010},
volume = {31},
pages = {1800--1804},
number = {10},
month = oct,
abstract = {The genetic component of colorectal cancer (CRC) predisposition has
been only partially explained. We recently suggested that a subtle
decrease in the expression of one allele of the TGFBR1 gene was a
heritable quantitative trait predisposing to CRC. Here, we refined
the measurements of allele-specific expression (ASE) of TGFBR1 in
a population-based series of CRC patients and controls. Five single-nucleotide
polymorphisms (SNPs) in the 3'-untranslated region of the gene were
genotyped and used for ASE determination by pyrosequencing. After
eliminating non-informative samples and samples with RNA of insufficient
quality 109 cases and 125 controls were studied. Allelic ratios ranged
between 0.74 and 1.69 without evidence of bimodality or cutoff points
for ASE' versus non-ASE'. Treating ASE as a continuous variable,
cases had non-significantly different values than controls (P = 0.081
when comparing means by permutation test). However, cases had significantly
higher ASE values when comparing medians by permutation test (P =
0.0027) and when using Wilcoxon test (P = 0.0094). We conclude that
with the present-day technology, ASE differences between individuals
and between cases and controls are too subtle to be used to assess
CRC risk. More advanced technology is expected to resolve this issue
as well as the low informativity caused by the limited heterozygosity
of transcribed SNPs.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/31/10/1800}
}
@ARTICLE{Tomte2006,
author = {Tomte, Laurice T. and Annatshah, Yaser and Schluter, Nadine K. and
Miosge, Nicolai and Herken, Rainer and Quondamatteo, Fabio},
title = {Hematopoietic Cells Are a Source of Nidogen-1 and Nidogen-2 during
Mouse Liver Development},
journal = {J. Histochem. Cytochem.},
year = {2006},
volume = {54},
pages = {593--604},
number = {5},
month = may,
abstract = {Nidogen-1 and -2 are key components of basement membranes (BMs). Despite
the presence of nidogen molecules in the parenchyma of the developing
liver, no BMs are formed therein. This suggests that, in the liver,
nidogens may also have functions other than BM formation. As a first
step toward the elucidation of the possible cell biological functions
of nidogens in the developing liver, we aimed to study their cellular
origin. We localized expression of nidogen-1 and nidogen-2 on prenatal
days 12, 14, and 16 in the developing mouse liver using in situ hybridization
at the light and electron microscopic level and light microscopic
immunohistochemistry. Our results show that nidogens are produced
both in portal anlagen and in the parenchyma during liver development.
In the parenchyma, transcripts can be found in hepatocytes, precursors
of stellate cells, endothelial cells and, most interestingly, hematopoietic
cells. Using real-time PCR, we found that the gene expression for
both proteins shows a decrease from day 14 to day 16 concomitant
with a decrease in the hepatic hematopoiesis. We suggest that nidogens
may, to some extent, take part in the regulation of hepatic hematopoiesis.
(J Histochem Cytochem 54:593-604, 2006)},
url = {http://www.jhc.org/cgi/content/abstract/54/5/593}
}
@ARTICLE{Tonacchera2009,
author = {Tonacchera, Massimo and De Marco, Giuseppina and Agretti, Patrizia
and Montanelli, Lucia and Di Cosmo, Caterina and Freitas Ferreira,
Andrea Claudia and Dimida, Antonio and Ferrarini, Eleonora and Ramos,
Helton Estrela and Ceccarelli, Claudia and Brozzi, Federica and Pinchera,
Aldo and Vitti, Paolo},
title = {Identification and Functional Studies of Two New Dual-Oxidase 2 (DUOX2)
Mutations in a Child with Congenital Hypothyroidism and a Eutopic
Normal-Size Thyroid Gland},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {4309--4314},
number = {11},
month = nov,
abstract = {Context: Some cases of congenital hypothyroidism (CH) are associated
with a gland of normal size. Objective: To explore the cause of organification
defect in one child with CH and a eutopic thyroid gland, genetic
analyses of TPO, DUOX2, and DUOXA2 genes were performed. Patient:
One child with CH, a eutopic thyroid gland, and a partial organification
defect was shown after 123I scintigraphy and perchlorate test. Methods:
In the child with the organification defect, TPO, DUOX2, and DUOXA2
genes were analyzed. The functional activity of the DUOX2 mutants
was studied after expression in eukaryotic cells. Results: No TPO
or DUOXA2 gene mutations were identified. Direct sequencing of the
DUOX2 gene revealed a compound heterozygous genotype for S911L and
C1052Y substitutions. S911L and C1052Y caused a partial defect in
H2O2 production after transient expression in HeLa cells. Conclusions:
We performed a genetic analysis in one child with CH and a eutopic
thyroid gland. Two new mutations in DUOX2 gene responsible for the
partial deficit in the organification process were identified.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/11/4309}
}
@ARTICLE{Tonacchera2007,
author = {Tonacchera, Massimo and Di Cosmo, Caterina and De Marco, Giuseppina
and Agretti, Patrizia and Banco, Mariaelena and Perri, Anna and Gianetti,
Elena and Montanelli, Lucia and Vitti, Paolo and Pinchera, Aldo},
title = {Identification of TSH receptor mutations in three families with resistance
to TSH},
journal = {Clinical Endocrinology},
year = {2007},
volume = {67},
pages = {712--718},
number = {5},
abstract = {Summary Objective  Genetic analysis of the TSH receptor gene in
seven subjects with subclinical hypothyroidism (SH), in whom the
diagnosis of autoimmune thyroid disease had been excluded by laboratory
and instrumental techniques currently available. Patients  Three
families where different members (2 children and 5 adults) affected
by SH were studied. Genetic analysis  Genomic DNA was extracted
from peripheral lymphocytes and the entire coding sequence of the
TSHr gene was sequenced. pSVL-TSHr construct harbouring a Q8fsX62
insertion was obtained by site-directed mutagenesis. COS-7 cells
transfected with wild-type and mutant receptor were used for binding
studies, flow cytometry, and cyclic AMP (cAMP) determination. Results 
A four base pair (bp) duplication in position 41 (41TGCAins), leading
to a premature stop of translation at codon 62 (Q8fsX62), was found
to be heterozygous in the proband, the father and the sister in Family
1. In Family 2 the proband and the sister were heterozygous for the
mutation D410N. In Family 3 the proband and the father were heterozygous
for the mutation P162A. After transfection in COS-7 cells, the mutant
receptor Q8fsX62 displayed a low expression at the cell surface,
and a reduced response to bovine TSH (bTSH) in terms of cAMP production.
Conclusions  We identified TSH receptor mutations in seven members
of three families with subclinical hypothyroidism.},
issn = {1365-2265},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2265.2007.02950.x}
}
@ARTICLE{Tone2008,
author = {Tone, Alicia A. and Begley, Heather and Sharma, Monika and Murphy,
Joan and Rosen, Barry and Brown, Theodore J. and Shaw, Patricia A.},
title = {Gene Expression Profiles of Luteal Phase Fallopian Tube Epithelium
from BRCA Mutation Carriers Resemble High-Grade Serous Carcinoma},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {4067--4078},
number = {13},
month = jul,
abstract = {Purpose: To identify molecular alterations potentially involved in
predisposition to adnexal serous carcinoma (SerCa) in the nonmalignant
fallopian tube epithelium (FTE) of BRCA1/2 mutation carriers, given
recent evidence implicating the distal FTE as a common source for
SerCa. Experimental Design: We obtained and compared gene expression
profiles of laser capture microdissected nonmalignant distal FTE
from 12 known BRCA1/2 mutation carriers (FTEb) and 12 control women
(FTEn) during the luteal and follicular phase, as well as 13 high-grade
tubal and ovarian SerCa. Results: Gene expression profiles of tubal
and ovarian SerCa specimens were indistinguishable by unsupervised
cluster analysis and significance analysis of microarrays. FTEb samples
as a group, and four individual FTEb samples from the luteal phase
in particular, clustered closely with SerCa rather than normal control
FTE. Differentially expressed genes from these four samples relative
to other FTEb samples, as well as differentially expressed genes
in all FTEb luteal samples relative to follicular samples, were mapped
to the I2D protein-protein interaction database, revealing a complex
network affecting signaling pathways previously implicated in tumorigenesis.
Two candidates, disabled homolog 2 mitogen-responsive phosphoprotein
(DAB2) and Ski-like (SKIL), were further validated by real-time reverse
transcription-PCR and tissue arrays. FTEb luteal and SerCa samples
expressed higher levels of oncogenic SKIL and decreased levels of
tumor suppressor DAB2, relative to FTEb follicular samples. Conclusions:
These findings support a common molecular pathway for adnexal SerCa
and implicate factors associated with the luteal phase in predisposition
to ovarian cancer in BRCA mutation carriers.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/13/4067}
}
@ARTICLE{Tonelli2008,
author = {Tonelli, L. H. and Stiller, J. and Rujescu, D. and Giegling, I. and
Schneider, B. and Maurer, K. and Schnabel, A. and Möller, H.-J.
and Chen, H. H. and Postolache, T. T.},
title = {Elevated cytokine expression in the orbitofrontal cortex of victims
of suicide},
journal = {Acta Psychiatrica Scandinavica},
year = {2008},
volume = {117},
pages = {198--206},
number = {3},
abstract = {Objective:  Based on the reported association between cytokines
with depression and suicide, and evidence of increased markers of
inflammation in the brain of suicide victims, the present study examined
the expression of cytokines in the orbitofrontal cortex of suicide
victims. Method:  In a postmortem sample obtained from the Brodman
area 11 of suicides (n = 34) and controls (n = 17), real-time
RT-PCR was used to compare the expression of mRNA species for tumor
necrosis factor-α (TNF-α), interleukin (IL)-1β, 4, 5, 6, and 13.
Results:  Increased expression of IL-4 was found in women suicide
victims and IL-13 in men suicide victims. Elevated but not significant
cytokine expression was also observed for TNF-α in women suicide
victims. Conclusion:  To our knowledge, these results provide the
first evidence of the presence of mRNA transcripts of type 2 T-helper
cytokines in the human orbitofrontal cortex and their increased expression
in the brain of suicides.},
issn = {1600-0447},
keywords = {suicide, postmortem, gene expression, brain, neuroimmune},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0447.2007.01128.x}
}
@ARTICLE{TonettodeFreitas2011,
author = {Tonetto de Freitas, Sergio and Padda, Malkeet and Wu, Qingyu and
Park, Sunghun and Mitcham, Elizabeth J.},
title = {Dynamic Alternations in Cellular and Molecular Components during
Blossom-End Rot Development in Tomatoes Expressing sCAX1, a Constitutively
Active Ca2+/H+ Antiporter from Arabidopsis},
journal = {Plant Physiology},
year = {2011},
volume = {156},
pages = {844-855},
number = {2},
abstract = {Although calcium (Ca) concentration in cellular compartments has been
suggested to be tightly regulated, Ca deficiency disorders such as
blossom-end rot (BER) in tomato (Solanum lycopersicum) fruit may
be induced by abnormal regulation of Ca partitioning and distribution
in the cell. The objectives of this work were to analyze the effects
of high expression of the constitutively functional Arabidopsis (Arabidopsis
thaliana) Ca2+/H+ exchanger (sCAX1) tonoplast protein in tomato fruit
on cellular Ca partitioning and distribution, membrane integrity,
and the transcriptional profile of genes potentially involved in
BER development. Wild-type and sCAX1-expressing tomato plants were
grown in a greenhouse. Wild-type plants did not develop BER, whereas
sCAX1-expressing plants reached 100% BER incidence at 15 d after
pollination. The sCAX1-expressing fruit pericarp had higher total
tissue and water-soluble Ca concentrations, lower apoplastic and
cytosolic Ca concentrations, higher membrane leakage, and Ca accumulation
in the vacuole of sCAX1-expressing cells. Microarray analysis of
healthy sCAX1-expressing fruit tissue indicated down-regulation of
genes potentially involved in BER development, such as genes involved
in membrane structure and repair and cytoskeleton metabolism, as
well as up-regulation of genes that may have limited BER damage expansion,
such as genes coding for heat shock proteins, glutathione S-transferases,
and peroxidases. The results indicate that the high expression of
the sCAX1 gene reduces cytosolic and apoplastic Ca concentrations,
affecting plasma membrane structure and leading to BER symptom development
in the fruit tissue.},
doi = {10.1104/pp.111.175208},
eprint = {http://www.plantphysiol.org/cgi/reprint/156/2/844.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/156/2/844}
}
@ARTICLE{Tong2006,
author = {Tong, Dan and Czerwenka, Klaus and Heinze, Georg and Ryffel, Martin
and Schuster, Eva and Witt, Armin and Leodolter, Sepp and Zeillinger,
Robert},
title = {Expression of KLF5 is a Prognostic Factor for Disease-Free Survival
and Overall Survival in Patients with Breast Cancer},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {2442--2448},
number = {8},
month = apr,
abstract = {Purpose: Kruppel-like factor (KLF5) is a cell growth mediator in various
epithelial cells. Higher KLF5 increases cell growth rate and leads
to transformed phenotypes. Because tumor cell proliferation is tightly
associated with tumor progression, and consequently, with survival
of cancer patients, we wanted to examine the prognostic value of
KLF5 gene expression for patients with breast cancer. Experimental
Design: The gene expression levels of KLF5, ER, PR, HER2, and MKI67
were quantified in the tumor tissues of 90 patients with breast cancer
and correlated with disease-free survival and overall survival of
the patients. The correlations of gene expression between KLF5 and
ER, PR, HER2, and MKI67 were analyzed. In addition, KLF5 expression
was also compared with clinical data and age of patients. Results:
Statistically significant correlations were found between gene expression
of KLF5 and both disease-free survival (univariate analysis) and
overall survival (univariate and multivariate analysis). Patients
with higher KLF5 expression had shorter disease-free survival and
overall survival time, whereas patients with lower KLF5 expression
had better survival. Moreover, KLF5 was also found to be positively
correlated with HER2 and MKI67, and negatively correlated with age
of the patients at diagnosis. Conclusion: The gene expression of
KLF5 is directly correlated with cell proliferation in vivo and is
a prognostic factor for patients with breast cancer. Patients with
higher KLF5 expression have shorter disease-free survival and overall
survival than patients with lower KLF5 expression. In addition, KLF5
has higher expression in patients ages [≤]50 years old than in
patients >50 years old.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/8/2442}
}
@ARTICLE{Tong2010,
author = {Tong, Dan and Heinze, Georg and Pils, Dietmar and Wolf, Andrea and
Singer, Christian and Concin, Nicole and Hofstetter, Gerda and Schiebel,
Ingrid and Rudas, Margaretha and Zeillinger, Robert},
title = {Gene expression of PMP22 is an independent prognostic factor for
disease-free and overall survival in breast cancer patients},
journal = {BMC Cancer},
year = {2010},
volume = {10},
pages = {682},
number = {1},
abstract = {BACKGROUND:Gene expression of peripheral myelin protein 22 (PMP22)
and the epithelial membrane proteins (EMPs) was found to be differentially
expressed in invasive and non-invasive breast cell lines in a previous
study. We want to evaluate the prognostic impact of the expression
of these genes on breast cancer.METHODS:In a retrospective multicenter
study, gene expression of PMP22 and the EMPs was measured in 249
primary breast tumors by real-time PCR. Results were statistically
analyzed together with clinical data.RESULTS:In univariable Cox regression
analyses PMP22 and the EMPs were not associated with disease-free
survival or tumor-related mortality. However, multivariable Cox regression
revealed that patients with higher than median PMP22 gene expression
have a 3.47 times higher risk to die of cancer compared to patients
with equal values on clinical covariables but lower PMP22 expression.
They also have a 1.77 times higher risk to relapse than those with
lower PMP22 expression. The proportion of explained variation in
overall survival due to PMP22 gene expression was 6.5% and thus PMP22
contributes equally to prognosis of overall survival as nodal status
and estrogen receptor status. Cross validation demonstrates that
5-years survival rates can be refined by incorporating PMP22 into
the prediction model.CONCLUSIONS:PMP22 gene expression is a novel
independent prognostic factor for disease-free survival and overall
survival for breast cancer patients. Including it into a model with
established prognostic factors will increase the accuracy of prognosis.},
doi = {10.1186/1471-2407-10-682},
issn = {1471-2407},
pubmedid = {21159173},
url = {http://www.biomedcentral.com/1471-2407/10/682}
}
@ARTICLE{Tonge2008,
author = {Tonge, David and Chan, Kevin and Zhu, Ning and Panjwani, Aliza and
Arno, Mathew and Lynham, Steven and Ward, Malcolm and Snape, Alison
and Pizzey, John},
title = {Enhancement of axonal regeneration by in vitro conditioning and its
inhibition by cyclopentenone prostaglandins},
journal = {J. Cell Sci.},
year = {2008},
volume = {121},
pages = {2565--2577},
number = {15},
month = aug,
abstract = {Axonal regeneration is enhanced by the prior `conditioning' of peripheral
nerve lesions. Here we show that Xenopus dorsal root ganglia (DRG)
with attached peripheral nerves (PN-DRG) can be conditioned in vitro,
thereafter showing enhanced neurotrophin-induced axonal growth similar
to preparations conditioned by axotomy in vivo. Actinomycin D inhibits
axonal outgrowth from freshly dissected PN-DRG, but not from conditioned
preparations. Synthesis of mRNAs that encode proteins necessary for
axonal elongation might therefore occur during the conditioning period,
a suggestion that was confirmed by oligonucleotide microarray analysis.
Culturing PN-DRG in a compartmentalized system showed that inhibition
of protein synthesis (but not RNA synthesis) in the distal nerve
impaired the conditioning response, suggesting that changes in gene
expression in cultured DRG depend on the synthesis and retrograde
transport of protein(s) in peripheral nerves. The culture system
was also used to demonstrate retrograde axonal transport of several
proteins, including thioredoxin (Trx). Cyclopentenone prostaglandins,
which react with Trx, blocked the in vitro conditioning effect, whereas
inhibition of other signalling pathways thought to be involved in
axonal regeneration did not. This suggests that Trx and/or other
targets of these electrophilic prostaglandins regulate axonal regeneration.
Consistent with this hypothesis, morpholino-induced suppression of
Trx expression in dissociated DRG neurons was associated with reduced
neurite outgrowth.},
url = {http://jcs.biologists.org/cgi/content/abstract/121/15/2565}
}
@ARTICLE{Top2011,
author = {Top, S. and Foulon, E. and Pignolet, B. and Deplanche, M. and Caubet,
C. and Tasca, C. and Bertagnoli, S. and Meyer, G. and Foucras, G.},
title = {Infection of Nonhost Species Dendritic Cells In Vitro with an Attenuated
Myxoma Virus Induces Gene Expression That Predicts Its Efficacy as
a Vaccine Vector},
journal = {J. Virol.},
year = {2011},
volume = {85},
pages = {12982-12994},
number = {24},
abstract = {Recombinant myxoma virus (MYXV) can be produced without a loss of
infectivity, and its highly specific host range makes it an ideal
vaccine vector candidate, although careful examination of its interaction
with the immune system is necessary. Similar to rabbit bone marrow-derived
dendritic cells (BM-DCs), ovine dendritic cells can be infected by
SG33, a MYXV vaccine strain, and support recombinant antigen expression.
The frequency of infected cells in the nonhost was lower and the
virus cycle was abortive in these cell types. Among BM-DC subpopulations,
Langerhans cell-like DCs were preferentially infected at low multiplicities
of infection. Interestingly, ovine BM-DCs remained susceptible to
MYXV after maturation, although apoptosis occurred shortly after
infection as a function of the virus titer. When gene expression
was assessed in infected BM-DC cultures, type I interferon (IFN)-related
and inflammatory genes were strongly upregulated. DC gene expression
profiles were compared with the profiles produced by other poxviruses
in interaction with DCs, but very few commonalities were found, although
genes that were previously shown to predict vaccine efficacy were
present. Collectively, these data support the idea that MYXV permits
efficient priming of adaptive immune responses and should be considered
a promising vaccine vector along with other poxviruses.},
doi = {10.1128/JVI.00128-11},
eprint = {http://jvi.asm.org/cgi/reprint/85/24/12982.pdf},
url = {http://jvi.asm.org/cgi/content/abstract/85/24/12982}
}
@ARTICLE{Topol2009,
author = {Topol, Lilia and Chen, Wen and Song, Hai and Day, Timothy F. and
Yang, Yingzi},
title = {Sox9 Inhibits Wnt Signaling by Promoting {beta}-Catenin Phosphorylation
in the Nucleus},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {3323--3333},
number = {5},
month = jan,
abstract = {Chondrocyte fate determination and maintenance requires Sox9, an intrinsic
transcription factor, but is inhibited by Wnt/{beta}-catenin signaling
activated by extrinsic Wnt ligands. Here we explored the underlying
molecular mechanism by which Sox9 antagonizes the Wnt/{beta}-catenin
signaling in chondrocyte differentiation. We found that Sox9 employed
two distinct mechanisms to inhibit Wnt/{beta}-catenin signaling:
the Sox9 N terminus is necessary and sufficient to promote {beta}-catenin
degradation, whereas the C terminus is required to inhibit {beta}-catenin
transcriptional activity without affecting its stability. Sox9 binds
to {beta}-catenin and components of the {beta}-catenin "destruction
complex," glycogen synthase kinase 3 and {beta}-transducin repeat
containing protein, to promote their nuclear localization. Independent
of its DNA binding ability, nuclear localization of Sox9 is both
necessary and sufficient to enhance {beta}-catenin phosphorylation
and its subsequent degradation. Thus, one mechanism whereby Sox9
regulates chondrogenesis is to promote efficient {beta}-catenin phosphorylation
in the nucleus. This mechanism may be broadly employed by other intrinsic
cell fate determining transcription factors to promptly turn off
extrinsic inhibitory Wnt signaling mediated by {beta}-catenin.},
url = {http://www.jbc.org/cgi/content/abstract/284/5/3323}
}
@ARTICLE{Torbica2010,
author = {Torbica, Aleksandra M. and ZÌŒivancÌŒev, Dragan R. and NikolicÌ?,
Zorica T. and Ä?orÄ‘evicÌ?, Vuk B. and Nikolovski, Branislava G.},
title = {Advantages of the Lab-on-a-Chip Method in the Determination of the
Kunitz Trypsin Inhibitor in Soybean Varieties},
journal = {Journal of Agricultural and Food Chemistry},
year = {2010},
volume = {58},
pages = {7980-7985},
number = {13},
doi = {10.1021/jf100830m},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf100830m},
url = {http://pubs.acs.org/doi/abs/10.1021/jf100830m}
}
@ARTICLE{Torchia2007,
author = {Torchia, Enrique C. and Boyd, Kelli and Rehg, Jerold E. and Qu, Chunxu
and Baker, Suzanne J.},
title = {EWS/FLI-1 Induces Rapid Onset of Myeloid/Erythroid Leukemia in Mice},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {7918--7934},
number = {22},
month = nov,
abstract = {EWS/FLI-1 is a chimeric oncogene generated by chromosomal translocation
in Ewing tumors, a family of poorly differentiated pediatric tumors
arising predominantly in bone but also in soft tissue. The fusion
gene combines sequences encoding a strong transactivating domain
from the EWS protein with the DNA binding domain of FLI-1, an ETS
transcription factor. A related fusion, TLS/ERG, has been found in
myeloid leukemia. To determine EWS/FLI-1 function in vivo, we engineered
mice with Cre-inducible expression of EWS/FLI-1 from the ubiquitous
Rosa26 locus. When crossed with Mx1-cre mice, Cre-mediated activation
of EWS/FLI-1 resulted in the rapid development of myeloid/erythroid
leukemia characterized by expansion of primitive mononuclear cells
causing hepatomegaly, splenomegaly, severe anemia, and death. The
disease could be transplanted serially into naive recipients. Gene
expression profiles of primary and transplanted animals were highly
similar, suggesting that activation of EWS/FLI-1 was the primary
event leading to disease in this model. The Cre-inducible EWS/FLI-1
mouse provides a novel model system to study the contribution of
this oncogene to malignant disease in vivo.},
url = {http://mcb.asm.org/cgi/content/abstract/27/22/7918}
}
@ARTICLE{Tordera2011,
author = {Tordera, R.M. and Garcia-García, A.L. and Elizalde, N. and Segura,
V. and Aso, E. and Venzala, E. and Ramírez, M.J. and Del Rio, J.},
title = {Chronic stress and impaired glutamate function elicit a depressive-like
phenotype and common changes in gene expression in the mouse frontal
cortex},
journal = {European Neuropsychopharmacology},
year = {2011},
volume = {21},
pages = {23--32},
number = {1},
month = jan,
abstract = {Major depression might originate from both environmental and genetic
risk factors. The environmental chronic mild stress (CMS) model mimics
some environmental factors contributing to human depression and induces
anhedonia and helplessness. Mice heterozygous for the synaptic vesicle
protein (SVP) vesicular glutamate transporter 1 (VGLUT1) have been
proposed as a genetic model of deficient glutamate function linked
to depressive-like behaviour. Here, we aimed to identify, in these
two experimental models, gene expression changes in the frontal cortex,
common to stress and impaired glutamate function. Both VGLUT1+/-
and CMS mice showed helpless and anhedonic-like behavior. Microarray
studies in VGLUT1+/- mice revealed regulation of genes involved in
apoptosis, neurogenesis, synaptic transmission, protein metabolic
process or learning and memory. In addition, RT-PCR studies confirmed
gene expression changes in several glutamate, GABA, dopamine and
serotonin neurotransmitter receptors. On the other hand, CMS affected
the regulation of 147 transcripts, some of them involved in response
to stress and oxidoreductase activity. Interestingly, 52 genes were
similarly regulated in both models. Specifically, a dowregulation
in genes that promote cell proliferation (Anapc7), cell growth (CsnK1g1),
cell survival (Hdac3), and inhibition of apoptosis (Dido1) was observed.
Genes linked to cytoskeleton (Hspg2, Invs), psychiatric disorders
(Grin1, MapK12) or an antioxidant enzyme (Gpx2) were also downregulated.
Moreover, genes that inhibit the MAPK pathways (Dusp14), stimulate
oxidative metabolism (Eif4a2) and enhance glutamate transmission
(Rab8b) were upregulated. We suggest that these genes could form
part of the altered "molecular context" underlying depressive-like
behaviour in animal models. The clinical relevance of these findings
is discussed.},
booktitle = {NewMood (New Molecules for Mood Disorders)},
issn = {0924-977X},
keywords = {Chronic mild stress, VGLUT1, Major depression, Animal models, Gene
expression},
url = {http://www.sciencedirect.com/science/article/pii/S0924977X10001434}
}
@ARTICLE{Tordjman2012,
author = {Tordjman, Joan and Divoux, Adeline and Prifti, Edi and Poitou, Christine
and Pelloux, Veronique and Hugol, Danielle and Basdevant, Arnaud
and Bouillot, Jean-Luc and Chevallier, Jean-Marc and Bedossa, Pierre
and Guerre-Millo, Michèle and Clement, Karine},
title = {Structural and inflammatory heterogeneity in subcutaneous adipose
tissue: relation with liver histopathology in morbid obesity},
journal = {J Hepatol},
year = {2012},
pages = {--},
month = jan,
abstract = {In addition to total body fat, the regional distribution and inflammatory
status of enlarged adipose tissue are strongly associated with metabolic
co-morbidities of obesity. We recently showed that the severity of
histological liver lesions related to obesity increases with the
amounts of macrophage accumulation in visceral adipose tissue (VAT),
while no association was found with the subcutaneous adipose tissue
(SAT). In the abdominal region, SAT is anatomically divided in two
layers, i.e. superficial (sSAT) and deep (dSAT) SAT. The aim of the
present study was to test the hypothesis that these distinct compartments
differentially contribute to hepatic alterations in obesity. Biopsies
of liver, sSAT, dSAT and VAT were collected in 45 subjects with morbid
obesity (Age 43.7 ± 1.6 years; BMI 48.5 ± 1.2 kg/m2) during bariatric
surgery. Large scale gene expression analysis was performed to identify
the pathways that discriminate sSAT from dSAT. Adipose tissue macrophages
were quantified by immunohistochemistry using HAM56 antibody in subjects
scored for liver histopathology. An inflammatory gene pattern discriminates
between sSAT and dSAT. dSAT displayed an intermediate level of macrophage
accumulation between sSAT and VAT. The abundance of macrophages in
dSAT, but not in sSAT, was significantly increased in patients with
non-alcoholic steatohepatitis (NASH) and/or fibroinflammatory hepatic
lesions. These data show distinct gene signature and macrophage abundance
in the two compartments of SAT, with dSAT more closely related to
VAT than to sSAT in terms of inflammation and relation with the severity
of liver diseases in morbid obesity.},
issn = {0168-8278},
keywords = {Obesity, Adipose tissue subcompartment, Nash, Inflammation, Macrophages},
publisher = {Elsevier,},
refid = {S0168-8278(12)00054-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0168827812000542?showall=true}
}
@ARTICLE{Torisu-Itakura2007,
author = {Torisu-Itakura, Hitoe and Lee, Jonathan H. and Scheri, Randall P.
and Huynh, Young and Ye, Xing and Essner, Richard and Morton, Donald
L.},
title = {Molecular Characterization of Inflammatory Genes in Sentinel and
Nonsentinel Nodes in Melanoma},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {3125--3132},
number = {11},
month = jun,
abstract = {Purpose: Identification of regional node metastasis is important for
accurate staging and optimal treatment of early melanoma. We hypothesize
that the nodal profile of immunoregulatory cytokines can confirm
the identity of the first tumor-draining regional node, i.e., the
sentinel node (SN) and indicate its tumor status. Experimental Design:
RNA was extracted from freshly dissected and preserved nodal tissue
of 13 tumor-negative SNs, 10 tumor-positive SNs (micrometastases
<2 mm), and 11 tumor-negative non-SNs (NSN). RNA was converted into
cDNA and then amplified by PCR. Expression of 96 cytokines and chemokines
was assessed using cDNA microarray and compared by using hierarchical
clustering. Results: Fifty-seven genes were expressed at significantly
(P < 0.05) different levels in SNs and NSNs (4 genes had higher expression,
and 53 genes had lower expression in SNs). Expression levels of interleukin-13
(IL-13), leptin, lymphotoxin {beta} receptor (LTbR), and macrophage
inflammatory protein 1b (MIP1b) were significantly higher (P < 0.04,
P < 0.01, P < 0.05, and P < 0.01, respectively), and expression level
of IL-11Ra was lower (P < 0.03) for tumor-positive as compared with
tumor-negative SN. Receiver-operator characteristics curve analyses
showed that the area under the curve (AUC) for IL-13, leptin, LTbR,
MIP1b, and IL-11Ra was 0.79, 0.83, 0.75, 0.81, and 0.77, respectively.
The AUC for the five genes in combination was 0.973, suggesting high
concordance of gene-expression profiles with SN staging. Conclusions:
SNs have a different immunoregulatory cytokine profile than NSNs.
The cytokine profile of tumor-positive SNs; increased expression
of IL-13, leptin, LTbR, and MIP1b and decreased expression of IL-11Ra,
may provide clues to the local tumor lymph node interaction seen
in the earliest steps of melanoma metastasis.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/11/3125}
}
@ARTICLE{Torkildsen2010,
author = {Torkildsen, Øivind and Stansberg, Christine and Angelskår, Solveig
M. and Kooi, Evert-Jan and Geurts, Jeroen J.G. and Van Der Valk,
Paul and Myhr, Kjell-Morten and Steen, Vidar M. and Bø, Lars},
title = {Upregulation of Immunoglobulin-related Genes in Cortical Sections
from Multiple Sclerosis Patients},
journal = {Brain Pathology},
year = {2010},
volume = {20},
pages = {720--729},
number = {4},
abstract = {Abstract Multiple sclerosis (MS) is a demyelinating disease of the
central nervous system (CNS). Microarray-based global gene expression
profiling is a promising method, used to study potential genes involved
in the pathogenesis of the disease. In the present study, we have
examined global gene expression in normal-appearing gray matter and
gray matter lesions from the cortex of MS patients, and compared
them with cortical gray matter samples from controls. We observed
a massive upregulation of immunoglobulin (Ig)-related genes in cortical
sections of MS patients. Using immunohistochemistry, the activation
of Ig genes seems to occur within plasma cells in the meninges. As
synthesis of oligoclonal IgGs has been hypothesized to be caused
by the activation of Epstein–Barr virus (EBV)-infected B-cells,
we screened the brain samples for the presence of EBV by real-time
quantitative polymerase chain reaction (qPCR) and immunohistochemistry,
but no evidence of active or latent EBV infection was detected. This
study demonstrates that genes involved in the synthesis of Igs are
upregulated in MS patients and that this activation is caused by
a small number of meningeal plasma cells that are not infected by
EBV. The findings indicate that the Ig-producing B-cells found in
the cerebrospinal fluid (CSF) of MS patients could have meningeal
origin.},
issn = {1750-3639},
keywords = {EBV, Epstein–Barr virus, immunoglobulin, microarray, multiple sclerosis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2009.00343.x}
}
@ARTICLE{Toro2010,
author = {del Toro, Raquel and Prahst, Claudia and Mathivet, Thomas and Siegfried,
Geraldine and Kaminker, Joshua S. and Larrivee, Bruno and Breant,
Christiane and Duarte, Antonio and Takakura, Nobuyuki and Fukamizu,
Akiyoshi and Penninger, Josef and Eichmann, Anne},
title = {Identification and functional analysis of endothelial tip cell-enriched
genes},
journal = {Blood},
year = {2010},
volume = {116},
pages = {4025--4033},
number = {19},
month = nov,
abstract = {Sprouting of developing blood vessels is mediated by specialized motile
endothelial cells localized at the tips of growing capillaries. Following
behind the tip cells, endothelial stalk cells form the capillary
lumen and proliferate. Expression of the Notch ligand Delta-like-4
(Dll4) in tip cells suppresses tip cell fate in neighboring stalk
cells via Notch signaling. In DLL4+/- mouse mutants, most retinal
endothelial cells display morphologic features of tip cells. We hypothesized
that these mouse mutants could be used to isolate tip cells and so
to determine their genetic repertoire. Using transcriptome analysis
of retinal endothelial cells isolated from DLL4+/- and wild-type
mice, we identified 3 clusters of tip cell-enriched genes, encoding
extracellular matrix degrading enzymes, basement membrane components,
and secreted molecules. Secreted molecules endothelial-specific molecule
1, angiopoietin 2, and apelin bind to cognate receptors on endothelial
stalk cells. Knockout mice and zebrafish morpholino knockdown of
apelin showed delayed angiogenesis and reduced proliferation of stalk
cells expressing the apelin receptor APJ. Thus, tip cells may regulate
angiogenesis via matrix remodeling, production of basement membrane,
and release of secreted molecules, some of which regulate stalk cell
behavior.},
comment = {10.1182/blood-2010-02-270819},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/116/19/4025}
}
@ARTICLE{Torocsik2010,
author = {Torocsik, Daniel and Barath, Monika and Benko, Szilvia and Szeles,
Lajos and Dezso, Balazs and Poliska, Szilard and Hegyi, Zoltan and
Homolya, Laszlo and Szatmari, Istvan and Lanyi, Arpad and Nagy, Laszlo},
title = {Activation of Liver X Receptor Sensitizes Human Dendritic Cells to
Inflammatory Stimuli},
journal = {J. Immunol.},
year = {2010},
volume = {184},
pages = {5456--5465},
number = {10},
month = may,
abstract = {Dendritic cells (DCs) respond to changes in their lipid environment
by altering gene expression and immunophenotype. Some of these alterations
are mediated via the nuclear receptor superfamily. However, little
is known about the contribution of liver X receptor (LXR) to DC biology.
In this study, we present a systematic analysis of LXR, activated
by synthetic ligands or naturally occurring oxysterols in developing
human monocyte-derived DCs. We found that LXRs are present and can
be activated throughout DC differentiation in monocyte- and blood-derived
DCs. Administration of LXR-specific natural or synthetic activators
induced target gene expression accompanied by increased expression
of DC maturation markers, such as CD80 and CD86. In mature DCs, LXR
activation augmented the production of inflammatory cytokines IL-12,
TNF-{alpha}, IL-6, and IL-8 and resulted in an increased capacity
to activate CD4+ T cell proliferation upon ligation with TLR4 or
TLR3 ligands. These effects appear to be underpinned by prolonged
NF-{kappa}B signaling. Supporting such an inflammatory role, we found
that LXR positive DCs are present in reactive lymph nodes in vivo.
We propose that activation of LXR represents a novel lipid-signaling
paradigm that alters the inflammatory response of human DCs.},
url = {http://www.jimmunol.org/cgi/content/abstract/184/10/5456}
}
@ARTICLE{Torrentino-Madamet2011,
author = {Torrentino-Madamet, Marylin and Almeras, Lionel and Desplans, Jerome
and Priol, Yannick and Belghazi, Maya and Pophillat, Matthieu and
Fourquet, Patrick and Jammes, Yves and Parzy, Daniel},
title = {Global response of Plasmodium falciparum to hyperoxia: a combined
transcriptomic and proteomic approach},
journal = {Malaria Journal},
year = {2011},
volume = {10},
pages = {4},
number = {1},
abstract = {BACKGROUND:Over its life cycle, the Plasmodium falciparum parasite
is exposed to different environmental conditions, particularly to
variations in O2 pressure. For example, the parasite circulates in
human venous blood at 5% O2 pressure and in arterial blood, particularly
in the lungs, at 13% O2 pressure. Moreover, the parasite is exposed
to 21% O2 levels in the salivary glands of mosquitoes.METHODS:To
study the metabolic adaptation of P. falciparum to different oxygen
pressures during the intraerythrocytic cycle, a combined approach
using transcriptomic and proteomic techniques was undertaken.RESULTS:Even
though hyperoxia lengthens the parasitic cycle, significant transcriptional
changes were detected in hyperoxic conditions in the late-ring stage.
Using PS 6.0TM software (Ariadne Genomics) for microarray analysis,
this study demonstrate up-expression of genes involved in antioxidant
systems and down-expression of genes involved in the digestive vacuole
metabolism and the glycolysis in favour of mitochondrial respiration.
Proteomic analysis revealed increased levels of heat shock proteins,
and decreased levels of glycolytic enzymes. Some of this regulation
reflected post-transcriptional modifications during the hyperoxia
response.CONCLUSIONS:These results seem to indicate that hyperoxia
activates antioxidant defence systems in parasites to preserve the
integrity of its cellular structures. Moreover, environmental constraints
seem to induce an energetic metabolism adaptation of P. falciparum.
This study provides a better understanding of the adaptive capabilities
of P. falciparum to environmental changes and may lead to the development
of novel therapeutic targets.},
doi = {10.1186/1475-2875-10-4},
issn = {1475-2875},
pubmedid = {21223545},
url = {http://www.malariajournal.com/content/10/1/4}
}
@ARTICLE{Torres2010,
author = {Torres, Davi Coe and Adaui, Vanessa and Ribeiro-Alves, Marcelo and
Romero, Gustavo A.S. and Arévalo, Jorge and Cupolillo, Elisa and
Dujardin, Jean-Claude},
title = {Targeted gene expression profiling in Leishmania braziliensis and
Leishmania guyanensis parasites isolated from Brazilian patients
with different antimonial treatment outcomes},
journal = {Infection, Genetics and Evolution},
year = {2010},
volume = {10},
pages = {727--733},
number = {6},
month = aug,
abstract = {In Brazil, cutaneous leishmaniasis represents a serious public health
problem, and chemotherapy is an important element of the clinical
management of this disease. However, treatment efficacy is variable,
a phenomenon that might be due to host and parasite (e.g., drug resistance)
factors. To better understand the possible contribution of parasite
factors to this phenomenon, we characterised 12 Leishmania braziliensis
(LB) and 25 Leishmania guyanensis (LG) isolates collected from patients
experiencing different antimonial treatment outcomes. For each isolate,
promastigote cultures were grown in duplicate and were harvested
at the late-log and stationary phases of growth. The RNA expression
profiles of six genes encoding proteins with roles in antimony metabolism
(AQP1, MRPA, GSH1, GSH2, TRYR and TDR1) were assessed by means of
real-time quantitative PCR. Molecular data were compared to the clinical
phenotypes. Within LB, we did not find statistically significant
differences in the expression levels of the examined genes among
isolates from patients with different treatment outcomes. In LG,
GSH1 (encoding gamma-glutamylcysteine synthetase, [gamma]-GCS) was
overexpressed in therapeutic failure isolates regardless of the growth
curve phase. This finding reveals the predictive potential of promastigote
expression curves for the prognosis of cutaneous leishmaniasis caused
by LG in Brazil.},
booktitle = {MEEGID IX, M. Tibayrenc},
issn = {1567-1348},
keywords = {Cutaneous leishmaniasis, Treatment failure, Targeted gene expression
profiling, Leishmania braziliensis, Leishmania guyanensis},
url = {http://www.sciencedirect.com/science/article/B6W8B-5033XWX-4/2/a09ec6d07fb45addcb217911198a8878}
}
@ARTICLE{Tortosa2011,
author = {Tortosa, Raul and Castells, Xavier and Vidal, Enric and Costa, Carme
and Ruiz de Villa, Maria and Sanchez, Alex and Barcelo, Anna and
Torres, Juan and Pumarola, Marti and Arino, Joaquin},
title = {Central nervous system gene expression changes in a transgenic mouse
model for bovine spongiform encephalopathy},
journal = {Veterinary Research},
year = {2011},
volume = {42},
pages = {109},
number = {1},
abstract = {Gene expression analysis has proven to be a very useful tool to gain
knowledge of the factors involved in the pathogenesis of diseases,
particularly in the initial or preclinical stages. With the aim of
finding new data on the events occurring in the Central Nervous System
in animals affected with Bovine Spongiform Encephalopathy, a comprehensive
genome wide gene expression study was conducted at different time
points of the disease on mice genetically modified to model the bovine
species brain in terms of cellular prion protein. An accurate analysis
of the information generated by microarray technique was the key
point to assess the biological relevance of the data obtained in
terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation
of the microarray technique was achieved by RT-PCR confirming the
RNA change and immunohistochemistry techniques that verified that
expression changes were translated into variable levels of protein
for selected genes. Our study reveals changes in the expression of
genes, some of them not previously associated with prion diseases,
at early stages of the disease previous to the detection of the pathological
prion protein, that might have a role in neuronal degeneration and
several transcriptional changes showing an important imbalance in
the Central Nervous System homeostasis in advanced stages of the
disease. Genes whose expression is altered at early stages of the
disease should be considered as possible therapeutic targets and
potential disease markers in preclinical diagnostic tool development.
Genes non-previously related to prion diseases should be taken into
consideration for further investigations.},
doi = {10.1186/1297-9716-42-109},
issn = {1297-9716},
pubmedid = {22035425},
url = {http://www.veterinaryresearch.org/content/42/1/109}
}
@ARTICLE{Tosetto2009,
author = {Tosetto, E and Ceol, M and Mezzabotta, F and Ammenti, A and Peruzzi,
L and Caruso, MR and Barbano, G and Vezzoli, G and Colussi, G and
Vergine, G and Giordano, M and Glorioso, N and Degortes, S and Soldati,
L and Sayer, J and D'Angelo, A and Anglani, F},
title = {Novel mutations of the CLCN5 gene including a complex allele and
A 5′ UTR mutation in Dent disease 1},
journal = {Clinical Genetics},
year = {2009},
volume = {76},
pages = {413--416},
number = {4},
issn = {1399-0004},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-0004.2009.01212.x}
}
@ARTICLE{Tosetto2006,
author = {Tosetto, Enrica and Ghiggeri, Gian Marco and Emma, Francesco and
Barbano, Giancarlo and Carrea, Alba and Vezzoli, Giuseppe and Torregrossa,
Rossella and Cara, Marilena and Ripanti, Gabriele and Ammenti, Anita
and Peruzzi, Licia and Murer, Luisa and Ratsch, Ilse Maria and Citron,
Lorenzo and Gambaro, Giovanni and D'angelo, Angela and Anglani, Franca},
title = {Phenotypic and genetic heterogeneity in Dent's disease--the results
of an Italian collaborative study},
journal = {Nephrol. Dial. Transplant.},
year = {2006},
volume = {21},
pages = {2452--2463},
number = {9},
month = sep,
abstract = {Background. Dent's disease is an inherited tubulopathy caused by CLCN5
gene mutations. While a typical phenotype characterized by low-molecular-weight
(LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis,
rickets and progressive renal failure in various combinations often
enables a clinical diagnosis, less severe sub-clinical cases may
go under-diagnosed. Methods. By single-strand conformation polymorphism
analysis and direct sequencing, we screened 40 male patients from
40 unrelated families for CLCN5 gene mutations. Twenty-four of these
patients had the prominent features of Dent's disease, including
LMW proteinuria, hypercalciuria and nephrocalcinosis. Results. We
identified 24 mutations in the CLCN5 gene in 21/24 patients with
a typical phenotype and in 3/16 patients with a partial clinical
picture of Dent's disease. Overall, 10 novel CLCN5 mutations were
identified (E6fsX11, W58fsX97, 267 del E, Y272C, N340K, F444fsX448,
W547X, Q600X, IVS3 +2 G>C and IVS3 -1 G>A), extending the number
of mutations identified so far from 75 to 85. The CLCN5 coding sequence
was normal in three patients. In the group with an incomplete Dent's
disease phenotype, we detected two intronic mutations and one silent
substitution leading to the up regulation of an alternatively spliced
isoform. Conclusions. Our data confirm the genetic heterogeneity
of Dent's disease. In most classic cases, the clinical diagnosis
is confirmed by genetic tests.},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/21/9/2452}
}
@ARTICLE{Tosolini2011,
author = {Tosolini, Marie and Kirilovsky, Amos and Mlecnik, Bernhard and Fredriksen,
Tessa and Mauger, Stephanie and Bindea, Gabriela and Berger, Anne
and Bruneval, Patrick and Fridman, Wolf-Herman and Pages, Franck
and Galon, Jerome},
title = {Clinical Impact of Different Classes of Infiltrating T Cytotoxic
and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal
Cancer},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {1263--1271},
number = {4},
month = feb,
abstract = {The tumor microenvironment includes a complex network of immune T-cell
subpopulations. In this study, we systematically analyzed the balance
between cytotoxic T cells and different subsets of helper T cells
in human colorectal cancers and we correlated their impact on disease-free
survival. A panel of immune related genes were analyzed in 125 frozen
colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg,
Th1, and Th17 cells were also quantified in the center and the invasive
margin of the tumors. By hierarchical clustering of a correlation
matrix we identified functional clusters of genes associated with
Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2,
STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression
of the Th17 cluster had a poor prognosis, whereas patients with high
expression of the Th1 cluster had prolonged disease-free survival.
In contrast, none of the Th2 clusters were predictive of prognosis.
Combined analysis of cytotoxic/Th1 and Th17 clusters improved the
ability to discriminate relapse. In situ analysis of the density
of IL17+ cells and CD8+ cells in tumor tissues confirmed the results.
Our findings argue that functional Th1 and Th17 clusters yield opposite
effects on patient survival in colorectal cancer, and they provide
complementary information that may improve prognosis. Cancer Res;
71(4); 1263-71. (C)2011 AACR.},
comment = {10.1158/0008-5472.CAN-10-2907},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/4/1263}
}
@ARTICLE{Tost2010,
author = {Tost, Jörg and Gut, Ivo G.},
title = {Molecular Techniques for DNA Methylation Studies},
journal = {Molecular Diagnostics},
year = {2010},
volume = {NA},
pages = {199--228},
address = {San Diego},
booktitle = {Molecular Diagnostics (Second Edition)},
editor = {Patrinos, George P. and Ansorge, Wilhelm J.},
issn = {978-0-12-374537-8},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B9FC0-4Y59TWJ-B/2/ef813a84f7921ce36d2f0dd4da6ee17e}
}
@ARTICLE{Tothill2008,
author = {Tothill, Richard W. and Tinker, Anna V. and George, Joshy and Brown,
Robert and Fox, Stephen B. and Lade, Stephen and Johnson, Daryl S.
and Trivett, Melanie K. and Etemadmoghadam, Dariush and Locandro,
Bianca and Traficante, Nadia and Fereday, Sian and Hung, Jillian
A. and Chiew, Yoke-Eng and Haviv, Izhak and Australian Ovarian Cancer
Study Group and Gertig, Dorota and deFazio, Anna and Bowtell, David
D.L.},
title = {Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer
Linked to Clinical Outcome},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {5198--5208},
number = {16},
month = aug,
abstract = {Purpose: The study aim to identify novel molecular subtypes of ovarian
cancer by gene expression profiling with linkage to clinical and
pathologic features. Experimental Design: Microarray gene expression
profiling was done on 285 serous and endometrioid tumors of the ovary,
peritoneum, and fallopian tube. K-means clustering was applied to
identify robust molecular subtypes. Statistical analysis identified
differentially expressed genes, pathways, and gene ontologies. Laser
capture microdissection, pathology review, and immunohistochemistry
validated the array-based findings. Patient survival within k-means
groups was evaluated using Cox proportional hazards models. Class
prediction validated k-means groups in an independent dataset. A
semisupervised survival analysis of the array data was used to compare
against unsupervised clustering results. Results: Optimal clustering
of array data identified six molecular subtypes. Two subtypes represented
predominantly serous low malignant potential and low-grade endometrioid
subtypes, respectively. The remaining four subtypes represented higher
grade and advanced stage cancers of serous and endometrioid morphology.
A novel subtype of high-grade serous cancers reflected a mesenchymal
cell type, characterized by overexpression of N-cadherin and P-cadherin
and low expression of differentiation markers, including CA125 and
MUC1. A poor prognosis subtype was defined by a reactive stroma gene
expression signature, correlating with extensive desmoplasia in such
samples. A similar poor prognosis signature could be found using
a semisupervised analysis. Each subtype displayed distinct levels
and patterns of immune cell infiltration. Class prediction identified
similar subtypes in an independent ovarian dataset with similar prognostic
trends. Conclusion: Gene expression profiling identified molecular
subtypes of ovarian cancer of biological and clinical importance.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/16/5198}
}
@ARTICLE{Totoki2011,
author = {Totoki, Yasushi and Tatsuno, Kenji and Yamamoto, Shogo and Arai,
Yasuhito and Hosoda, Fumie and Ishikawa, Shumpei and Tsutsumi, Shuichi
and Sonoda, Kohtaro and Totsuka, Hirohiko and Shirakihara, Takuya
and Sakamoto, Hiromi and Wang, Linghua and Ojima, Hidenori and Shimada,
Kazuaki and Kosuge, Tomoo and Okusaka, Takuji and Kato, Kazuto and
Kusuda, Jun and Yoshida, Teruhiko and Aburatani, Hiroyuki and Shibata,
Tatsuhiro},
title = {High-resolution characterization of a hepatocellular carcinoma genome},
journal = {Nat Genet},
year = {2011},
volume = {43},
pages = {464--469},
number = {5},
month = may,
comment = {10.1038/ng.804},
issn = {1061-4036},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/ng.804}
}
@ARTICLE{Tougan2008,
author = {Tougan, Takahiro and Okuzaki, Daisuke and Nojima, Hiroshi},
title = {Chum-RNA allows preparation of a high-quality cDNA library from a
single-cell quantity of mRNA without PCR amplification},
journal = {Nucleic Acids Res.},
year = {2008},
volume = {36},
pages = {e92--},
number = {15},
month = sep,
abstract = {Linear RNA amplification using T7 RNA polymerase is useful in genome-wide
analysis of gene expression using DNA microarrays, but exponential
amplification using polymerase chain reaction (PCR) is still required
for cDNA library preparation from single-cell quantities of RNA.
We have designed a small RNA molecule called chum-RNA that has enabled
us to prepare a single-cell cDNA library after four rounds of T7-based
linear amplification, without using PCR amplification. Chum-RNA drove
cDNA synthesis from only 0.49 femtograms of mRNA (730 mRNA molecules)
as a substrate, a quantity that corresponds to a minor population
of mRNA molecules in a single mammalian cell. Analysis of the independent
cDNA clone of this library (6.6 x 105 cfu) suggests that 30-fold
RNA amplification occurred in each round of the amplification process.
The size distribution and representation of mRNAs in the resulting
one-cell cDNA library retained its similarity to that of the million-cell
cDNA library. The use of chum-RNA might also facilitate reactions
involving other DNA/RNA modifying enzymes whose Michaelis constant
(Km) values are around 1 mM, allowing them to be activated in the
presence of only small quantities of substrate.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/36/15/e92}
}
@ARTICLE{Tougan2008a,
author = {Tougan, Takahiro and Onda, Hiroaki and Okuzaki, Daisuke and Kobayashi,
Shigeto and Hashimoto, Hiroshi and Nojima, Hiroshi},
title = {Focused Microarray Analysis of Peripheral Mononuclear Blood Cells
from Churg-Strauss Syndrome Patients},
journal = {DNA Res},
year = {2008},
volume = {15},
pages = {103--114},
number = {2},
month = apr,
abstract = {DNA diagnostics are useful but are hampered by difficult ethical issues.
Moreover, it cannot provide enough information on the environmental
factors that are important for pathogenesis of certain diseases.
However, this is not a problem for RNA diagnostics, which evaluate
the expression of the gene in question. We here report a novel RNA
diagnostics tool that can be employed with peripheral blood mononuclear
cells (PBMCs). To establish this tool, we identified 290 genes that
are highly expressed in normal PBMCs but not in TIG-1, a normal human
fibroblast cell. These genes were entitled PREP after predominantly
expressed in PBMC and included 50 uncharacterized genes. We then
conducted PREP gene-focused microarray analysis on PBMCs from seven
cases of Churg-Strauss syndrome (CSS), which is a small-vessel necrotizing
vasculitis. We found that PREP135 (coactosin-like protein), PREP77
(prosaposin), PREP191 (cathepsin D), PREP234 (c-fgr), and PREP136
(lysozyme) were very highly up-regulated in all seven CSS patients.
Another 28 genes were also up-regulated, albeit more moderately,
and three were down-regulated in all CSS patients. The nature of
these up- and down-regulated genes suggest that the immune systems
of the patients are activated in response to invading microorganisms.
These observations indicate that focused microarray analysis of PBMCs
may be a practical, useful, and low-cost bedside diagnostics tool.},
url = {http://dnaresearch.oxfordjournals.org/cgi/content/abstract/15/2/103}
}
@ARTICLE{Toullec2010,
author = {Toullec, Aurore and Gerald, Damien and Despouy, Gilles and Bourachot,
Brigitte and Cardon, Melissa and Lefort, Sylvain and Richardson,
Marion and Rigaill, Guillem and Parrini, Maria-Carla and Lucchesi,
Carlo and Bellanger, Dorine and Stern, Marc-Henri and Dubois, Thierry
and Sastre-Garau, Xavier and Delattre, Olivier and Vincent-Salomon,
Anne and Mechta-Grigoriou, Fatima},
title = {Oxidative stress promotes myofibroblast differentiation and tumour
spreading},
journal = {EMBO Mol Med},
year = {2010},
volume = {2},
pages = {211--230},
number = {6},
abstract = {Abstract 10.1002/emmm.201000073.abs JunD regulates genes involved
in antioxidant defence. We took advantage of the chronic oxidative
stress resulting from junD deletion to examine the role of reactive
oxygen species (ROS) in tumour development. In a model of mammary
carcinogenesis, junD inactivation increased tumour incidence and
revealed an associated reactive stroma. junD-inactivation in the
stroma was sufficient to shorten tumour-free survival rate and enhance
metastatic spread. ROS promoted conversion of fibroblasts into highly
migrating myofibroblasts through accumulation of the hypoxia-inducible
factor (HIF)-1α transcription factor and the CXCL12 chemokine. Accordingly,
treatment with an antioxidant reduced the levels of HIF and CXCL12
and numerous myofibroblast features. CXCL12 accumulated in the stroma
of HER2-human breast adenocarcinomas. Moreover, HER2 tumours exhibited
a high proportion of myofibroblasts, which was significantly correlated
to nodal metastases. Interestingly, this subset of tumours exhibited
a significant nuclear exclusion of JunD and revealed an associated
oxido-reduction signature, further demonstrating the relevance of
our findings in human cancers. Collectively, our data uncover a new
mechanism by which oxidative stress increases the migratory properties
of stromal fibroblasts, which in turn potentiate tumour dissemination.},
issn = {1757-4684},
keywords = {AP-1, SDF-1, HIF-1, stroma, metastasis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/emmm.201000073}
}
@ARTICLE{Toulza2005,
author = {Toulza, Frédéric and Eliaou, Jean-François and Pinet, Valérie},
title = {Breast tumor cell soluble factors induce monocytes to produce angiogenic
but not angiostatic CXC chemokines},
journal = {Int. J. Cancer},
year = {2005},
volume = {115},
pages = {429--436},
number = {3},
abstract = {Abstract 10.1002/ijc.20705.abs Tumor cells are known to interact closely
with nontumoral infiltrating cells in order to grow and proliferate.
Monocyte-derived cells constitute a major component of the tumoral
infiltrate and a high level of these cells has been associated with
increased tumor growth and poor prognosis in patients with breast
cancer. For their growth and metastatic propagation, solid tumors
are dependant on angiogenesis and accumulated evidences suggest that
monocyte-derived cells could also play an important role in this
phenomenon. However, the precise nature of proangiogenic factors
secreted by these cells in breast carcinomas, and their direct influence
on vessel formation, has not been determined. In the present study,
we show that soluble factors secreted by breast tumor cells induce
monocytes to produce a variety of proangiogenic CXC chemokines without
secretion of angiostatic CXC chemokines. Using in vitro tubule formation
in Matrigel, we demonstrated that the CXC chemokines secreted by
MTSs (monocytes cultured with tumor cell supernatants) were able
to induce microvessel formation. The profile of secreted CXC chemokines
was characteristic for each tumor cell line or fresh tumor cells.
This last result points out that a precise profiling of secreted
proangiogenic factors inside the tumor, by tumor cells themselves
or tumor-infiltrating monocyte-derived cells, is important for a
precise targeting of therapeutic agents against neovascularization.
© 2005 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {monocytes/macrophages, tumor immunity, chemokines, human},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.20705}
}
@ARTICLE{Toussaint2009,
author = {Toussaint, Jérôme and Sieuwerts, Anieta and Haibe-Kains, Benjamin
and Desmedt, Christine and Rouas, Ghizlane and Harris, Adrian and
Larsimont, Denis and Piccart, Martine and Foekens, John and Durbecq,
Virginie and Sotiriou, Christos},
title = {Improvement of the clinical applicability of the Genomic Grade Index
through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded
tissues},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {424},
number = {1},
abstract = {BACKGROUND:Proliferation and tumor differentiation captured by the
genomic grade index (GGI) are important prognostic indicators in
breast cancer (BC) especially for the estrogen receptor positive
(ER+) disease. The aims of this study were to convert this microarray
index to a qRT-PCR assay (PCR-GGI), which could be realized on formalin
fixed paraffin embedded samples (FFPE), and to assess its prognostic
performance and predictive value of clinical benefit in early and
advanced ER+ BC patients treated with tamoxifen.METHODS:The accuracy
and concordance of the PCR-GGI with the GGI was assessed using BC
patients for which frozen and FFPE tissues as well as microarray
data were available (n = 19). The evaluation of the prognostic value
of the PCR-GGI was assessed on FFPE material using a consecutive
series of 212 systemically treated early BC patients. The predictive
performance for tamoxifen benefit was assessed using two ER+ BC populations
treated either with adjuvant tamoxifen only (n = 77+139) or first-line
tamoxifen for advanced disease (n = 270).RESULTS:The PCR-GGI is based
on the expression of 8 genes (4 representative of the GGI and 4 reference
genes). A significant correlation was observed between the microarray-derived
GGI and the qRT-PCR assay using frozen (? = 0.95, p < 10E-06) and
FFPE material (? = 0.89, p < 10E-06). The prognostic performance
of the PCR-GGI was confirmed on FFPE samples (HRunivar. = 1.89; [95CI:1.01-3.54],
p = 0.05). The PCR-GGI further identified two subgroups of patients
with statistically different time to distant metastasis free survival
(DMFS) across the two cohorts of ER+ BC patients treated with adjuvant
tamoxifen. Additionally, the PCR-GGI was associated with response
to tamoxifen in the advanced setting (HRunivar. = 1.98; [95CI:1.51-2.59],
p = 6.9E-07).CONCLUSION:PCR-GGI recapitulates in an accurate and
reproducible manner the performances of the GGI using frozen and
FFPE samples.},
doi = {10.1186/1471-2164-10-424},
issn = {1471-2164},
pubmedid = {19744330},
url = {http://www.biomedcentral.com/1471-2164/10/424}
}
@ARTICLE{Towle2011,
author = {Towle, David W. and Henry, Raymond P. and Terwilliger, Nora B.},
title = {Microarray-detected changes in gene expression in gills of green
crabs (Carcinus maenas) upon dilution of environmental salinity},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2011},
volume = {6},
pages = {115--125},
number = {2},
month = jun,
abstract = {The interaction between environmental salinity and gene expression
was studied in gills of the euryhaline green shore crab Carcinus
maenas. A 4462-feature oligonucleotide microarray was used to analyze
changes in transcript abundance in posterior ion-transporting gills
at 8 time periods following transfer of animals from 32 to 10 or
15 ppt salinity. Transcripts encoding Na+/K+-ATPase [alpha]-subunit
and cytoplasmic carbonic anhydrase were upregulated with significant
changes between 6 and 24 h post-transfer. Other transport proteins
showing similar transcriptional upregulation were an organic cation
transporter, a sodium/glucose cotransporter, an endomembrane protein
associated with regulating plasma membrane protein composition, and
a voltage-gated calcium channel. Transport proteins showing little
transcriptional response included Na+/H+ exchanger, Na+/K+/2Cl- cotransporter,
and V-type H+-ATPase B subunit, all of which have been implicated
in osmoregulatory ion transport across crustacean gill. Interestingly,
there was little affect of salinity dilution on transcriptional expression
of stress proteins, suggesting that salinity acclimation is part
of normal physiology for C. maenas. Expression of transcripts encoding
a variety of mitochondrial proteins was significantly upregulated
between 4 days and 7 days post-transfer, consistent with the proliferation
of mitochondria-rich cells previously observed at this time.},
issn = {1744-117X},
keywords = {Crustacean, Osmoregulation, Ion transporters, Stress proteins, Mitochondrial
proteins},
url = {http://www.sciencedirect.com/science/article/pii/S1744117X10001048}
}
@ARTICLE{Towle2006,
author = {Towle, David W. and Smith, Christine M.},
title = {Gene discovery in Carcinus maenas and Homarus americanus via expressed
sequence tags},
journal = {Integr. Comp. Biol.},
year = {2006},
volume = {46},
pages = {912--918},
number = {6},
month = dec,
abstract = {Expressed sequence tags (ESTs) were produced for normalized cDNA libraries
prepared from several tissues of 2 marine crustaceans, the green
shore crab Carcinus maenas and the American lobster Homarus americanus.
Tissues represented in the Carcinus library were anterior and posterior
gills, hypodermis, heart, hepatopancreas, antennal gland, brain,
testis, and skeletal muscle, obtained from animals acclimated to
35 and 10{per thousand} salinity. Tissues represented in the Homarus
library were gill, epipodite, branchiostegite, heart, ovary, testis,
antennal gland, skeletal muscle, hepatopancreas, and brain, obtained
from intermolt and post-molt animals. Directional libraries from
oligo-dT-primed cDNA were constructed in the pCMVsport6.1 vector
and normalized by self-subtraction at 2 different Cot values. Randomly
picked clones were single-pass sequenced from the 5' end. Raw sequence
data were trimmed and prepared for submission to dbEST using phred,
cross-match, and blastx protocols embedded within trace2dbest software.
A total of 4604 Homarus and 12 401 Carcinus ESTs produced 540 and
2651 clusters, respectively, as determined by TIGR Gene Index Clustering
software. Gene Ontology analysis with reference to a Drosophila melanogaster
database using GOblet revealed 187 positive hits (35%) with the Homarus
clusters and 1037 positive hits (39%) with the Carcinus clusters.
Combining the number of assembled sequences with the number of singlets
obtained after cluster analysis suggested that transcripts representing
as much as 25% of the total number of genes in Carcinus have been
isolated.},
url = {http://icb.oxfordjournals.org/cgi/content/abstract/46/6/912}
}
@ARTICLE{Toyooka2003,
author = {Toyooka, Kazuhiko and Watanabe, Yuichiro and Iritani, Shuji and Shimizu,
Eiji and Iyo, Masaomi and Nakamura, Ryosuke and Asama, Koue and Makifuchi,
Takao and Kakita, Akiyoshi and Takahashi, Hitoshi and Someya, Toshiyuki
and Nawa, Hiroyuki},
title = {A decrease in interleukin-1 receptor antagonist expression in the
prefrontal cortex of schizophrenic patients},
journal = {Neuroscience Research},
year = {2003},
volume = {46},
pages = {299--307},
number = {3},
month = jul,
abstract = {Interleukin-1 (IL-1) mediates psychological stress responses by regulating
monoamine metabolism and secretion of corticotropin-releasing factor,
and is therefore, implicated in various psychiatric diseases. To
evaluate the contribution of IL-1 signaling to the brain pathology
of schizophrenia, we measured protein and/or mRNA levels for IL-1[beta]
and endogenous IL-1 receptor antagonist (IL-1RA) in the postmortem
brain tissues of prefrontal and parietal cortex, putamen, and hypothalamus.
Both protein and mRNA levels of IL-1RA were specifically decreased
in the prefrontal cortex of schizophrenic patients, whereas IL-1[beta]
levels were not significantly altered in all the regions examined.
The IL-1RA decrease was not correlated with the dose of antipsychotics
given to patients. There was no influence of this illness on protein
levels for IL-1 receptor type 1 in the prefrontal cortex, either.
In contrast, IL-1RA serum levels were increased in schizophrenic
patients, especially in drug-free patients, as reported previously.
These findings suggest that chronic schizophrenia down-regulates
IL-1RA production the prefrontal cortex, irrespective of its impact
on the periphery. IL-1RA reduction might reflect an immunopathologic
trait of the prefrontal region in schizophrenic patients.},
issn = {0168-0102},
keywords = {Cytokine, IL-1, IL-1RA, Inflammation, Postmortem brain, Prefrontal
cortex, Schizophrenia},
url = {http://www.sciencedirect.com/science/article/B6T0H-48FCJCC-1/2/7893e533831182fe81a02e9338aa7529}
}
@ARTICLE{Tozakidou2010,
author = {Tozakidou, Magdalini and Goltz, Diane and Hagenström, Till and Budack,
Mareike K. and Vitzthum, Helga and Szlachta, Kamila and Bähring,
Robert and Ehmke, Heimo},
title = {Molecular and functional remodeling of Ito by angiotensin II in the
mouse left ventricle},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2010},
volume = {48},
pages = {140--151},
number = {1},
month = jan,
abstract = {The transient outward potassium current (Ito) in cardiac myocytes
is mainly mediated by members of the Kv4 subfamily of voltage-gated
potassium channels. Several in vitro studies have shown that angiotensin
II (Ang II), which plays an important role in the development of
cardiac hypertrophy, rapidly downregulates Kv4.3 mRNA expression.
However, it is not clear whether Ang II regulates Ito in vivo and
whether this regulation may depend on alterations in Kv4.3 gene expression.
To address this question, we determined the effects of acute (24 h)
and chronic (14 days) exogenous infusions of Ang II on Ito and the
expression of its channel subunits in the mouse left ventricle. Ang
II rapidly increased blood pressure and reduced Kv4.2 but not Kv4.3
mRNA levels in the absence of cardiac hypertrophy. In response to
chronically elevated Ang II levels cardiac hypertrophy developed,
which was associated with a downregulation of Kv4.2 and Kv4.3 mRNA
levels, and an upregulation of Kv1.4 mRNA levels. In contrast, neither
KChIP2 mRNA levels nor amplitude or macroscopic inactivation kinetics
of Ito were affected by the acute or chronic Ang II treatments. Consistent
with the unchanged Ito amplitude, Kv4.2, Kv4.3, and KChIP protein
expression levels were similar after chronic Ang II and sham treatment.
Our findings demonstrate that elevations of Ang II concentrations
that induce hypertension and cardiac hypertrophy do not alter the
amplitude of Ito in the mouse left ventricle. Furthermore, they suggest
that functional expression of cardiac Ito in mice is stabilized by
KChIP2.},
booktitle = {Special Issue: Ion Channels},
issn = {0022-2828},
keywords = {Angiotensin II, Gene expression, Hypertrophy, Ito, Potassium channel},
url = {http://www.sciencedirect.com/science/article/pii/S0022282809003708}
}
@ARTICLE{Tozlu-Kara2007,
author = {Tozlu-Kara, S and Roux, V and Andrieu, C and Vendrell, J and Vacher,
S and Lazar, V and Spyratos, F and Tubiana-Hulin, M and Cohen, P
and Dessen, P and Lidereau, R and Bieche, I},
title = {Oligonucleotide microarray analysis of estrogen receptor {alpha}-positive
postmenopausal breast carcinomas: identification of HRPAP20 and TIMELESS
as outstanding candidate markers to predict the response to tamoxifen},
journal = {J. Mol. Endocrinol.},
year = {2007},
volume = {39},
pages = {305--318},
number = {4},
month = oct,
abstract = {The estrogen receptor {alpha} (ER{alpha}) status of breast tumors
is used to identify patients who may respond to endocrine agents
such as tamoxifen. However, ER{alpha} status alone is not perfectly
predictive, and there is a pressing need for more reliable markers
of endocrine responsiveness. In this aim, we used a two-step strategy.
We first screened genes of interest by a pangenomic 44 K oligonucleotide
microarray in a series of ten ER{alpha}-positive tumors from five
tamoxifen-treated postmenopausal patients who relapsed (distant metastasis)
and five tamoxifen-treated postmenopausal patients who did not relapse,
matched with respect to age, Scarff-Bloom-Richardson grade, lymph
node status, and macroscopic tumor size. Genes of interest (n=24)
were then investigated in an independent well-characterized series
of ER{alpha}-positive unilateral invasive primary breast tumors from
postmenopausal women who received tamoxifen alone as adjuvant hormone
therapy after primary surgery. We identified four genes (HRPAP20,
TIMELESS, PTPLB, and MGC29814) for which high mRNA levels were significantly
associated with shorter relapse-free survival (log-rank test). We
also showed that hormone-regulated proliferation-associated 20 kDa
protein (HRPAP20) and TIMELESS are 17{beta}-estradiol-regulated in
vitro and are ectopically expressed in OH-Tam-resistant cell lines.
In conclusion, these findings point to HRPAP20 and TIMELESS as promising
markers of tamoxifen resistance in women with ER{alpha}-positive
breast tumors.},
url = {http://jme.endocrinology-journals.org/cgi/content/abstract/39/4/305}
}
@ARTICLE{Trabzuni2011,
author = {Trabzuni, Daniah and Ryten, Mina and Walker, Robert and Smith, Colin
and Imran, Sabaena and Ramasamy, Adaikalavan and Weale, Michael E.
and Hardy, John},
title = {Quality control parameters on a large dataset of regionally dissected
human control brains for whole genome expression studies},
journal = {Journal of Neurochemistry},
year = {2011},
volume = {119},
pages = {275--282},
number = {2},
abstract = {J. Neurochem. (2011) 119, 275–282.AbstractWe are building an open-access
database of regional human brain expression designed to allow the
genome-wide assessment of genetic variability on expression. Array
and RNA sequencing technologies make assessment of genome-wide expression
possible. Human brain tissue is a challenging source for this work
because it can only be obtained several and variable hours post-mortem
and after varying agonal states. These variables alter RNA integrity
in a complex manner. In this report, we assess the effect of post-mortem
delay, agonal state and age on gene expression, and the utility of
pH and RNA integrity number as predictors of gene expression as measured
on 1266 Affymetrix Exon Arrays. We assessed the accuracy of the array
data using QuantiGene, as an independent non-PCR-based method. These
quality control parameters will allow database users to assess data
accuracy. We report that within the parameters of this study post-mortem
delay, agonal state and age have little impact on array quality,
array data are robust to variable RNA integrity, and brain pH has
only a small effect on array performance. QuantiGene gave very similar
expression profiles as array data. This study is the first step in
our initiative to make human, regional brain expression freely available.},
doi = {10.1111/j.1471-4159.2011.07432.x},
issn = {1471-4159},
keywords = {brain pH, microarray validation, post-mortem human brain, QTL, RIN,
RNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07432.x}
}
@ARTICLE{Trainor2007,
author = {Trainor, Brian C. and Hofmann, Hans A.},
title = {Somatostatin and somatostatin receptor gene expression in dominant
and subordinate males of an African cichlid fish},
journal = {Behavioural Brain Research},
year = {2007},
volume = {179},
pages = {314--320},
number = {2},
month = may,
abstract = {Somatostatin is a neuropeptide best known for its inhibitory effects
on growth hormone secretion and has recently been implicated in the
control of social behavior. Several somatostatin receptor subtypes
have been identified in vertebrates, but the functional basis for
this diversity is still unclear. Here we investigate the expression
levels of the somatostatin prepropeptide and two of its receptors,
sstR2, and sstR3, in the brains of socially dominant and subordinate
Astatotilapia burtoni males using real-time PCR. Dominant males had
higher somatostatin prepropeptide and sstR3 expression in hypothalamus
compared to subordinate males. Hypothalamic sstR2 expression did
not differ. There were no differences in gene expression in the telencephalon.
We also observed an interesting difference between dominants and
subordinates in the relationship between hypothalamic sstR2 expression
and body size. As would be predicted based on the inhibitory effects
of somatostatin on somatic growth, sstR2 expression was negatively
correlated with body size in dominant males. In contrast sstR2 expression
was positively correlated with body size in subordinate males. These
results suggest that in A. burtoni social status affects the relationships
between somatostatin prepropeptide and receptor gene expression in
the hypothalamus and the control of somatic growth.},
issn = {0166-4328},
keywords = {Aggression, Growth, Social behavior, Pre-optic area, Astatotilapia
burtoni},
url = {http://www.sciencedirect.com/science/article/B6SYP-4N3GF9V-1/2/bd507a35d34287a10e7dec7d5706de42}
}
@ARTICLE{Trainor2006,
author = {Trainor, Brian C. and Hofmann, Hans A.},
title = {Somatostatin Regulates Aggressive Behavior in an African Cichlid
Fish},
journal = {Endocrinology},
year = {2006},
volume = {147},
pages = {5119--5125},
number = {11},
month = nov,
abstract = {Animals respond to environmental and social change with plasticity
in the neural substrates underlying particular behavioral states.
In the African cichlid fish Astatotilapia burtoni, social dominance
status in males is accompanied by reduced somatic growth rate as
well as increased somatostatin neuron size in the preoptic area.
Although somatostatin is commonly studied within the context of growth,
we show here for the first time that this ancient neuropeptide also
plays a role in controlling social behavior. Somatostatin antagonists
increased aggressive behavior in a dose-dependent fashion and the
potent somatostatin agonist octreotide decreased aggression. We cloned
and sequenced the genes encoding two somatostatin receptor subtypes
in this species to study transcription in the gonads. When we examined
somatostatin receptor gene expression in testes, expression of the
somatostatin type 3 receptor was negatively correlated with an aggressive
display and androgen levels. However, octreotide treatment did not
reduce plasma testosterone or 11-ketotestosterone levels, suggesting
that the behavioral effects of somatostatin are not mediated by androgens.
These results show that somatostatin has important effects on social
behavior. In dominant male A. burtoni, somatostatin may function
to contain energetically costly processes such as somatic growth
and aggressive behavior.},
url = {http://endo.endojournals.org/cgi/content/abstract/147/11/5119}
}
@ARTICLE{Traka2005,
author = {Traka, Maria and Gasper, Amy V. and Smith, Julie A. and Hawkey, Chris
J. and Bao, Yongping and Mithen, Richard F.},
title = {Transcriptome Analysis of Human Colon Caco-2 Cells Exposed to Sulforaphane},
journal = {J. Nutr.},
year = {2005},
volume = {135},
pages = {1865--1872},
number = {8},
month = aug,
abstract = {Sulforaphane (SF), a dietary phytochemical obtained from broccoli,
has been implicated in several physiological processes consistent
with anticarcinogenic activity, including enhanced xenobiotic metabolism,
cell cycle arrest, and apoptosis. In this study, we report changes
in global gene expression in Caco-2 cells exposed to physiologically
appropriate concentrations of SF, through the use of replicated Affymetrix
array and RT-PCR experiments. After exposure to 50 {micro}mol/L SF,
106 genes exhibited a >2-fold increase in expression and 63 genes
exhibited a >2-fold decrease in expression. There were fewer changes
in gene expression at lower SF concentrations. The majority of these
genes had not previously been shown to be modulated by SF, suggesting
novel mechanisms of possible anticarcinogenic activity, including
induction of differentiation and modulation of fatty acid metabolism.
The changes in the expression of 10 of these genes, together with
4 additional genes of biological interest, were further quantified
in independent studies with RT-PCR. These genes include several that
have recently become associated with carcinogenesis, such as Kruppel-like
factor (KLF)4, a gut-enriched transcription factor associated with
induction of differentiation and reduction in cellular proliferation;
DNA (cytosine-5-)-methyltransferase 1, associated with methylation;
and {alpha}-methylacyl-CoA racemase (AMACR), a marker associated
with the development of colon and prostate cancer. The expression
of 5 of these genes [caudal type homeo box transcription factor 2
(CDX-2), KLF4, KLF5, cyclin-dependent kinase inhibitor 1A (p21),
and AMACR] was additionally studied after in vitro exposure to SF
of surgically resected healthy and cancerous colon tissue from each
of 3 patients. The study suggests the complex effects that SF has
on gene expression and highlights several potential mechanisms by
which the consumption of broccoli may reduce the risk of carcinogenesis.},
url = {http://jn.nutrition.org/cgi/content/abstract/135/8/1865}
}
@ARTICLE{Trakooljul2010,
author = {Trakooljul, N. and Hicks, J. A. and Liu, H.-C.},
title = {Identification of target genes and pathways associated with chicken
microRNA miR-143},
journal = {Animal Genetics},
year = {2010},
volume = {41},
pages = {357--364},
number = {4},
abstract = {Summary MicroRNA (miRNA) is a family of small regulatory RNAs that
post-transcriptionally regulate many biological functions including
growth and development. Recently, the expression of chicken miRNA
miR-143 was identified by using a deep sequencing approach. In other
vertebrate species, miR-143 functions as a regulator of adipocyte
differentiation and as a tumour suppressor. However, little is known
about the biological function(s) of miR-143 in chickens. To study
the functions of chicken miR-143, DNA microarray analysis and a dual
luciferase reporter assay were employed to identify genes directly
targeted by miR-143 as well as other biologically relevant genes.
Microarray analysis indicated that 124 genes were differentially
expressed upon in vitro anti-miR-143 treatment in embryonic chick
splenocytes (P-value cutoff <0.01). Many of these genes are associated
with cell proliferation, apoptosis and tumourigenesis. Six of the
up-regulated genes possess at least one potential miR-143 binding
site in their 3′UTRs, of these the binding sites of PYCR2, PSTPIP1
and PDCD5 were validated by an in vitro luciferase reporter assay.
In addition, several potential targets with important biological
functions were identified by the miRanda algorithm and experimentally
confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3,
which have conserved miR-143 binding sites across multiple vertebrate
species. Potential chicken specific miR-143 target sites were also
validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall,
the current study suggests that miR-143 is ubiquitously expressed
among tissues and is likely to be involved in the regulation of cell
proliferation and apoptosis.},
issn = {1365-2052},
keywords = {chicken, microRNA, miR-143},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2052.2009.02015.x}
}
@ARTICLE{Tramontana2008,
author = {Tramontana, S. and Bionaz, M. and Sharma, A. and Graugnard, D.E.
and Cutler, E.A. and Ajmone-Marsan, P. and Hurley, W.L. and Loor,
J.J.},
title = {Internal Controls for Quantitative Polymerase Chain Reaction of Swine
Mammary Glands During Pregnancy and Lactation},
journal = {Journal of Dairy Science},
year = {2008},
volume = {91},
pages = {3057--3066},
number = {8},
month = aug,
abstract = {High-throughput microarray analysis is an efficient means of obtaining
a genome-wide view of transcript profiles across physiological states.
However, quantitative PCR (qPCR) remains the chosen method for high-precision
mRNA abundance analysis. Essential for reliability of qPCR data is
normalization using appropriate internal control genes (ICG), which
is now, more than ever before, a fundamental step for accurate gene
expression profiling. We mined mammary tissue microarray data on
>13,000 genes at -34, -14, 0, 7, 14, 21, and 28 d relative to parturition
in 27 crossbred primiparous gilts to identify suitable ICG. Initial
analysis revealed TBK1, PCSK2, PTBP1, API5, VAPB, QTRT1, TRIM41,
TMEM24, PPP2R5B, and AP1S1 as the most stable genes (sample/reference = 1 ± 0.2).
We also included 9 genes previously identified as ICG in bovine mammary
tissue. Gene network analysis of the 19 genes identified AP1S1, API5,
MTG1, VAPB, TRIM41, MRPL39, and RPS15A as having no known co-regulation.
In addition, UXT and ACTB were added to this list, and mRNA abundance
of these 9 genes was measured by qPCR. Expression of all 9 of these
genes was decreased markedly during lactation. In a previous study
with bovine mammary tissue, mRNA of stably expressed genes decreased
during lactation due to a dilution effect brought about by large
increases in expression of highly abundant genes. To verify this
effect, highly abundant mammary genes such as CSN1S2, SCD, FABP3,
and LTF were evaluated by qPCR. The tested ICG had a negative correlation
with these genes, demonstrating a dilution effect in the porcine
mammary tissue. Gene stability analysis identified API5, VABP, and
MRPL39 as the most stable ICG in porcine mammary tissue and indicated
that the use of those 3 genes was most appropriate for calculating
a normalization factor. Overall, results underscore the importance
of proper validation of internal controls for qPCR and highlight
the limitations of using absence of time effects as the criteria
for selection of appropriate ICG. Further, we showed that use of
the same ICG from one organism might not be suitable for qPCR normalization
in other species.},
issn = {0022-0302},
keywords = {internal control gene, quantitative polymerase chain reaction},
url = {http://www.sciencedirect.com/science/article/B9887-4YBNWSX-G/2/fbbb8563366bc292770b17f8aa94d4ca}
}
@ARTICLE{Tran2011,
author = {Tran, J. and Waddell, L. and North, K.N. and Clarke, N.F.},
title = {P5.63. RNAlater® simplifies the transport of muscle sections for
mRNA analysis over long distances},
journal = {Neuromuscul Disord},
year = {2011},
volume = {21},
pages = {743--},
number = {9},
month = oct,
issn = {0960-8966},
publisher = {Pergamon Press,},
refid = {S0960-8966(11)01281-8},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0960896611012818?showall=true}
}
@ARTICLE{Tran2010a,
author = {Tran, K.V. and Nguyen, S.T.B. and Tran, T.H. and Nguyen, H.T. and
Vu, D.C. and Ta, V.T. and Matsuo, M.},
title = {P4.04 Deletion mutation analysis of dystrophin gene in Vietnamese
DMD patients – identification of female carriers in their families
by capillary electrophoresis},
journal = {Neuromuscul Disord},
year = {2010},
volume = {20},
pages = {659--},
number = {9},
month = oct,
issn = {0960-8966},
publisher = {Pergamon Press,},
refid = {S0960-8966(10)00471-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0960896610004712?showall=true}
}
@ARTICLE{Tran2010,
author = {Tran, Nguyet Thuy and Ayed, Ichraf and Pallandre, Antoine and Taverna,
Myriam},
title = {Recent innovations in protein separation on microchips by electrophoretic
methods: An update},
journal = {ELECTROPHORESIS},
year = {2010},
volume = {31},
pages = {147--173},
number = {1},
abstract = {Abstract 10.1002/elps.200900465.abs Lab-on-a-chip electrophoresis
is becoming increasingly useful for protein analysis, thanks to recent
developments in this field. This review is an update of the review
we published at the start of 2008 [Peng, Y., Pallandre, A., Tran,
N. T., Taverna, M., Electrophoresis 2008, 29, 156–177]. The superiority
of polymers for the manufacture of analytical microchips has been
confirmed. This trend implies several modifications to the processes
previously used with glass/silicon chips and requires a better understanding
of the interfacial phenomena of these materials. Significant progress
in chip-based techniques for protein analysis has been made in the
last 2 years. In addition to advances in traditional electrokinetic
modes, counter-flow gradient focusing techniques have emerged as
useful methods not only for separation, but also for the online preconcentration
of samples. This review, with more than 175 references, presents
recent advances and novel strategies for EOF measurement, surface
treatment, sample pretreatment, detection and innovations relating
to the different modes of separation.},
issn = {1522-2683},
keywords = {Chip, Detection, Electrophoretic separation, Miniaturization, Proteins},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200900465}
}
@ARTICLE{Tran2007,
author = {Tran, Phan-Kiet and Agardh, Hanna E. and Tran-Lundmark, Karin and
Ekstrand, Johan and Roy, Joy and Henderson, Bimma and Gabrielsen,
Anders and Hansson, Göran K. and Swedenborg, Jesper and Paulsson-Berne,
Gabrielle and Hedin, Ulf},
title = {Reduced perlecan expression and accumulation in human carotid atherosclerotic
lesions},
journal = {Atherosclerosis},
year = {2007},
volume = {190},
pages = {264--270},
number = {2},
month = feb,
abstract = {Heparan sulfate in the extracellular matrix of the artery wall has
been proposed to possess anti-atherogenic properties by interfering
with lipoprotein retention, suppression of inflammation, and inhibition
of smooth muscle cell growth. Previously, the amount of heparan sulfate
in atherosclerotic lesions from humans and animals has been shown
to be reduced but the identity or identities of the heparan sulfate
molecules being down regulated in this disease are not known. In
this study, atherosclerotic lesions were retrieved from 44 patients
undergoing surgery for symptomatic carotid stenosis. Normal iliac
arteries from organ donors were used as controls. Analysis of the
specimens by gene microarray showed a selective reduction in perlecan
gene expression, whereas, expression of the other heparan sulfate
proteoglycans in the artery wall, agrin and collagen XVIII, remained
unchanged. Expression of the large chondroitin sulfate proteoglycan,
versican, also remained unchanged. Real-time PCR confirmed the decrease
in perlecan gene expression and the unchanged expression of versican.
The findings were supported by immunohistochemical analysis demonstrating
a reduced accumulation of both perlecan core protein and heparan
sulfate in carotid lesions. The study demonstrates a reduction of
perlecan mRNA-expression and protein deposition in human atherosclerosis,
which in part explains the low levels of heparan sulfate in this
disease.},
issn = {0021-9150},
keywords = {Atherosclerosis, Perlecan, Heparan sulfate, Microarray, Carotid stenosis},
url = {http://www.sciencedirect.com/science/article/B6T12-4JRVD7N-8/2/e3f9b98624c44c8c2647c53757b4893d}
}
@ARTICLE{Tran2006,
author = {Tran, Van Khanh and Takeshima, Yasuhiro and Zhang, Zhujun and Yagi,
Mariko and Nishiyama, Atsushi and Habara, Yasuaki and Matsuo, Masafumi},
title = {Splicing analysis disclosed a determinant single nucleotide for exon
skipping caused by a novel intraexonic four-nucleotide deletion in
the dystrophin gene},
journal = {J. Med. Genet.},
year = {2006},
volume = {43},
pages = {924--930},
number = {12},
month = dec,
abstract = {Background: Mutations in exonic splicing enhancer sequences are known
to cause splicing errors. Although exonic splicing enhancers have
been identified as a stretch of purine-rich sequences, it has been
difficult to precisely pinpoint the determinant nucleotides in these
sequences. This article reports that a 4-bp deletion in exon 38 of
the dystrophin gene induced complete exon 38 skipping in vivo. Moreover,
the third nucleotide of the deletion was shown to be determinant
for the exonic splicing enhancer activity in in vivo splicing analysis
of hybrid minigenes encoding mutant exons. Method: Genomic DNA analysis
of a 2-year-old boy with a raised level of serum creatine kinase
yielded a 4-bp deletion 11 bp upstream of the 3' end of exon 38 of
the dystrophin gene (c. 5434-5437del TTCA), disrupting a predicted
SC35-binding site. Result: Interestingly, his dystrophin mRNA was
shown to completely lack exon 38 (exon 38- transcript). As the exon
38- transcript coded for a truncated dystrophin protein, this exon
skipping was determined to be a modifying factor of his phenotype.
In an in vivo splicing assay, a hybrid minigene encoding exon 38
with the 4-bp deletion was shown to induce complete exon 38 skipping,
confirming the deleted region as a splicing enhancer sequence. Site-directed
mutagenesis of the deleted sequence showed that the complete exon
38 skipping was caused by mutation of the third nucleotide position
of the deletion (C5436), whereas mutations at the other three nucleotide
positions induced partial exon skipping. Conclusion: Our results
underline the potential of understanding the regulation of exonic
splicing enhancer sequences and exon skipping therapy for treatment
of Duchenne's muscular dystrophy.},
url = {http://jmg.bmj.com/cgi/content/abstract/43/12/924}
}
@ARTICLE{Tran-Dinh2009,
author = {Tran-Dinh, N. and Carole, M. and Uthayakumaran, S. and Batey, I.L.
and Wrigley, C.W.},
title = {Rapid DNA-based identification of wheat and barley varieties},
journal = {Journal of Cereal Science},
year = {2009},
volume = {50},
pages = {388--391},
number = {3},
month = nov,
abstract = {Micro-fluidic capillary electrophoresis methodology was developed
to analyse grain DNA composition, thus to provide unequivocal distinction
between varieties of wheat (Triticum aestivum L.) and of barley (Hordeum
vulgare L.). This [`]Lab-on-a-chip' technology complements protein
composition analysis by micro-fluidic capillary electrophoresis,
which is already in routine use for variety identification. Whereas
it had been difficult to distinguish between some varieties by protein
analysis using the Lab-on-a-chip system, distinctions proved to be
possible using a combination of DNA extraction and microsatellite
analysis, taking advantage of the speed and convenience of DNA chips.
Several combinations of microsatellites permitted the DNA analysis
system to provide distinction between two wheat varieties and between
all but two (Chebec and Schooner) of the main eleven Australian barley
varieties (Arapiles, Baudin, Barque, Chebec, Gairdner, Grimmett,
Lindwall, Parwan, Schooner, Skiff and Sloop).},
booktitle = {Special Section: Enzymes in Grain Processing},
issn = {0733-5210},
keywords = {Micro-fluidic capillary electrophoresis, Lab-on-a-chip analysis, Grain
DNA, Microsatellite analysis},
url = {http://www.sciencedirect.com/science/article/B6WHK-4X5JR5M-1/2/17866eb4486fccbe0b60f713099ad6ee}
}
@ARTICLE{Tran-Lundmark2008,
author = {Tran-Lundmark, Karin and Tran, Phan-Kiet and Paulsson-Berne, Gabrielle
and Friden, Vincent and Soininen, Raija and Tryggvason, Karl and
Wight, Thomas N. and Kinsella, Michael G. and Boren, Jan and Hedin,
Ulf},
title = {Heparan Sulfate in Perlecan Promotes Mouse Atherosclerosis: Roles
in Lipid Permeability, Lipid Retention, and Smooth Muscle Cell Proliferation},
journal = {Circ. Res.},
year = {2008},
volume = {103},
pages = {43--52},
number = {1},
month = jul,
abstract = {Heparan sulfate (HS) has been proposed to be antiatherogenic through
inhibition of lipoprotein retention, inflammation, and smooth muscle
cell proliferation. Perlecan is the predominant HS proteoglycan in
the artery wall. Here, we investigated the role of perlecan HS chains
using apoE null (ApoE0) mice that were cross-bred with mice expressing
HS-deficient perlecan (Hspg2{Delta}3/{Delta}3). Morphometry of cross-sections
from aortic roots and en face preparations of whole aortas revealed
a significant decrease in lesion formation in ApoE0/Hspg2{Delta}3/{Delta}3
mice at both 15 and 33 weeks. In vitro, binding of labeled mouse
triglyceride-rich lipoproteins and human LDL to total extracellular
matrix, as well as to purified proteoglycans, prepared from ApoE0/Hspg2{Delta}3/{Delta}3
smooth muscle cells was reduced. In vivo, at 20 minutes influx of
human 125I-LDL or mouse triglyceride-rich lipoproteins into the aortic
wall was increased in ApoE0/Hspg2{Delta}3/{Delta}3 mice compared
to ApoE0 mice. However, at 72 hours accumulation of 125I-LDL was
similar in ApoE0/Hspg2{Delta}3/{Delta}3 and ApoE0 mice. Immunohistochemistry
of lesions from ApoE0/Hspg2{Delta}3/{Delta}3 mice showed decreased
staining for apoB and increased smooth muscle {alpha}-actin content,
whereas accumulation of CD68-positive inflammatory cells was unchanged.
We conclude that the perlecan HS chains are proatherogenic in mice,
possibly through increased lipoprotein retention, altered vascular
permeability, or other mechanisms. The ability of HS to inhibit smooth
muscle cell growth may also influence development as well as instability
of lesions.},
url = {http://circres.ahajournals.org/cgi/content/abstract/103/1/43}
}
@ARTICLE{Trandem2011,
author = {Trandem, Kathryn and Zhao, Jingxian and Fleming, Erica and Perlman,
Stanley},
title = {Highly Activated Cytotoxic CD8 T Cells Express Protective IL-10 at
the Peak of Coronavirus-Induced Encephalitis},
journal = {J. Immunol.},
year = {2011},
volume = {186},
pages = {3642--3652},
number = {6},
month = mar,
abstract = {Acute viral encephalitis requires rapid pathogen elimination without
significant bystander tissue damage. In this article, we show that
IL-10, a potent anti-inflammatory cytokine, is produced transiently
at the peak of infection by CD8 T cells in the brains of coronavirus-infected
mice. IL-10+CD8 and IL-10-CD8 T cells interconvert during acute disease,
possibly based on recent Ag exposure. Strikingly, IL-10+CD8 T cells
were more highly activated and cytolytic than IL-10-CD8 T cells,
expressing greater levels of proinflammatory cytokines and chemokines,
as well as cytotoxic proteins. Even though these cells are highly
proinflammatory, IL-10 expressed by these cells was functional. Furthermore,
IL-10 produced by CD8 T cells diminished disease severity in mice
with coronavirus-induced acute encephalitis, suggesting a self-regulatory
mechanism that minimizes immunopathological changes.},
comment = {10.4049/jimmunol.1003292},
url = {http://www.jimmunol.org/cgi/content/abstract/186/6/3642}
}
@ARTICLE{Tranter2010,
author = {Tranter, Michael and Ren, Xiaoping and Forde, Tiffany and Wilhide,
Michael E. and Chen, Jing and Sartor, Maureen A. and Medvedovic,
Mario and Jones, W. Keith},
title = {NF-?B driven cardioprotective gene programs; Hsp70.3 and cardioprotection
after late ischemic preconditioning},
journal = {J Mol Cell Cardiol},
year = {2010},
volume = {49},
pages = {664--672},
number = {4},
month = oct,
abstract = {It has been shown that the transcription factor NF-κB is necessary
for late phase cardioprotection after ischemic preconditioning (IPC)
in the heart, and yet is injurious after ischemia/reperfusion (I/R).
However the downstream gene expression programs that underlie the
contribution of NF-κB to cardioprotection after late IPC are incompletely
understood. The objective of this study was to delineate the specific
genes that are regulated by NF-κB immediately after a late IPC stimulus
and validate the methodology for the identification of NF-κB-dependent
genes that contribute to cardioprotection. A directed microarray
analysis identified 238 genes as up or downregulated in an NF-κB-dependent
manner 3.5h after late IPC. Among these are several genes previously
implicated in late IPC. Gene ontological analysis showed that the
most significant group of NF-κB-dependent genes are heat shock response
genes, including the genes encoding Hsp70.1 and Hsp70.3. Though an
Hsp70.1/70.3 double knockout failed to exhibit cardioprotection,
late IPC was intact in the Hsp70.1 single knockout. After I/R, the
Hsp70.1/70.3 double knockout and the Hsp70.1 single knockout had
significantly increased and reduced infarct size, respectively. These
results delineate the immediate NF-κB-dependent transcriptome after
late IPC. One of the major categories of NF-κB-dependent genes induced
by late IPC is the heat shock response. The results of infarct studies
confirm that Hsp70.3 is protective after IPC. However, though Hsp70.1
and Hsp70.3 are coordinately regulated, their functions are opposing
after I/R injury. ►Our results show that NF-κB regulates a unique
set of 238 genes after late IPC; several of these have been previously
implicated in late IPC. ►NF-κB regulates genes that fall primarily
into three functional categories; angiogenesis, programmed cell death
and heat shock response. â–ºOne of these genes, Hsp70.3, is shown
to be functionally cardioprotective, while the related Hsp70.1 is
not. â–ºHsp 70.1 is injurious after I/R injury, and thus functionally
opposed to Hsp70.3. ►NF-κB thus regulates multiple genes which
contribute to late IPC.},
issn = {0022-2828},
keywords = {Cardioprotection, Late ischemic preconditioning, NF-κB, Gene expression,
Heat shock protein 70},
publisher = {Academic Press.},
refid = {S0022-2828(10)00250-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0022282810002506?showall=true}
}
@ARTICLE{Trantow2011,
author = {Trantow, Colleen M. and Cuffy, Tryphena L. and Fingert, John H. and
Kuehn, Markus H. and Anderson, Michael G.},
title = {Microarray Analysis of Iris Gene Expression in Mice with Mutations
Influencing Pigmentation},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {237--248},
number = {1},
month = jan,
abstract = {Purpose.Several ocular diseases involve the iris, notably including
oculocutaneous albinism, pigment dispersion syndrome, and exfoliation
syndrome. To screen for candidate genes that may contribute to the
pathogenesis of these diseases, genome-wide iris gene expression
patterns were comparatively analyzed from mouse models of these conditions.
Methods.Iris samples from albino mice with a Tyr mutation, pigment
dispersion-prone mice with Tyrp1 and Gpnmb mutations, and mice resembling
exfoliation syndrome with a Lyst mutation were compared with samples
from wild-type mice. All mice were strain (C57BL/6J), age (60 days
old), and sex (female) matched. Microarrays were used to compare
transcriptional profiles, and differentially expressed transcripts
were described by functional annotation clustering using DAVID Bioinformatics
Resources. Quantitative real-time PCR was performed to validate a
subset of identified changes. Results.Compared with wild-type C57BL/6J
mice, each disease context exhibited a large number of statistically
significant changes in gene expression, including 685 transcripts
differentially expressed in albino irides, 403 in pigment dispersion-prone
irides, and 460 in exfoliative-like irides. Conclusions.Functional
annotation clusterings were particularly striking among the overrepresented
genes, with albino and pigment dispersion-prone irides both exhibiting
overall evidence of crystallin-mediated stress responses. Exfoliative-like
irides from mice with a Lyst mutation showed overall evidence of
involvement of genes that influence immune system processes, lytic
vacuoles, and lysosomes. These findings have several biologically
relevant implications, particularly with respect to secondary forms
of glaucoma, and represent a useful resource as a hypothesis-generating
dataset.},
comment = {10.1167/iovs.10-5479},
url = {http://www.iovs.org/cgi/content/abstract/52/1/237}
}
@ARTICLE{Trappe2011,
author = {Trappe, Todd A. and Carroll, Chad C. and Dickinson, Jared M. and
LeMoine, Jennifer K. and Haus, Jacob M. and Sullivan, Bridget E.
and Lee, Jonah D. and Jemiolo, Bozena and Weinheimer, Eileen M. and
Hollon, Chris J.},
title = {Influence of acetaminophen and ibuprofen on skeletal muscle adaptations
to resistance exercise in older adults},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {300},
pages = {R655--662},
number = {3},
month = mar,
abstract = {Evidence suggests that consumption of over-the-counter cyclooxygenase
(COX) inhibitors may interfere with the positive effects that resistance
exercise training has on reversing sarcopenia in older adults. This
study examined the influence of acetaminophen or ibuprofen consumption
on muscle mass and strength during 12 wk of knee extensor progressive
resistance exercise training in older adults. Thirty-six individuals
were randomly assigned to one of three groups and consumed the COX-inhibiting
drugs in double-blind placebo-controlled fashion: placebo (67 {+/-}
2 yr; n = 12), acetaminophen (64 {+/-} 1 yr; n = 11; 4 g/day), and
ibuprofen (64 {+/-} 1 yr; n = 13; 1.2 g/day). Compliance with the
resistance training program (100%) and drug consumption (via digital
video observation, 94%), and resistance training intensity were similar
(P > 0.05) for all three groups. Drug consumption unexpectedly increased
muscle volume (acetaminophen: 109 {+/-} 14 cm3, 12.5%; ibuprofen:
84 {+/-} 10 cm3, 10.9%) and muscle strength (acetaminophen: 19 {+/-}
2 kg; ibuprofen: 19 {+/-} 2 kg) to a greater extent (P < 0.05) than
placebo (muscle volume: 69 {+/-} 12 cm3, 8.6%; muscle strength: 15
{+/-} 2 kg), when controlling for initial muscle size and strength.
Follow-up analysis of muscle biopsies taken from the vastus lateralis
before and after training showed muscle protein content, muscle water
content, and myosin heavy chain distribution were not influenced
(P > 0.05) by drug consumption. Similarly, muscle content of the
two known enzymes potentially targeted by the drugs, COX-1 and -2,
was not influenced (P > 0.05) by drug consumption, although resistance
training did result in a drug-independent increase in COX-1 (32 {+/-}
8%; P < 0.05). Drug consumption did not influence the size of the
nonresistance-trained hamstring muscles (P > 0.05). Over-the-counter
doses of acetaminophen or ibuprofen, when consumed in combination
with resistance training, do not inhibit and appear to enhance muscle
hypertrophy and strength gains in older adults. The present findings
coupled with previous short-term exercise studies provide convincing
evidence that the COX pathway(s) are involved in the regulation of
muscle protein turnover and muscle mass in humans.},
comment = {10.1152/ajpregu.00611.2010},
url = {http://ajpregu.physiology.org/cgi/content/abstract/300/3/R655}
}
@ARTICLE{Trask2009,
author = {Trask, Heidi W. and Cowper-Sal-lari, Richard and Sartor, Maureen
A. and Gui, Jiang and Heath, Catherine V. and Renuka, Janhavi and
Higgins, Azara-Jane and Andrews, Peter and Korc, Murray and Moore,
Jason H. and Tomlinson, Craig R.},
title = {Microarray analysis of cytoplasmic versus whole cell RNA reveals
a considerable number of missed and false positive mRNAs},
journal = {RNA},
year = {2009},
volume = {15},
pages = {1917--1928},
number = {10},
month = oct,
abstract = {With no known exceptions, every published microarray study to determine
differential mRNA levels in eukaryotes used RNA extracted from whole
cells. It is assumed that the use of whole cell RNA in microarray
gene expression analysis provides a legitimate profile of steady-state
mRNA. Standard labeling methods and the prevailing dogma that mRNA
resides almost exclusively in the cytoplasm has led to the long-standing
belief that the nuclear RNA contribution is negligible. We report
that unadulterated cytoplasmic RNA uncovers differentially expressed
mRNAs that otherwise would not have been detected when using whole
cell RNA and that the inclusion of nuclear RNA has a large impact
on whole cell gene expression microarray results by distorting the
mRNA profile to the extent that a substantial number of false positives
are generated. We conclude that to produce a valid profile of the
steady-state mRNA population, the nuclear component must be excluded,
and to arrive at a more realistic view of a cell's gene expression
profile, the nuclear and cytoplasmic RNA fractions should be analyzed
separately.},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/15/10/1917}
}
@ARTICLE{Tree2009,
author = {Tree, Jai J. and Wang, Dai and McInally, Carol and Mahajan, Arvind
and Layton, Abigail and Houghton, Irene and Elofsson, Mikael and
Stevens, Mark P. and Gally, David L. and Roe, Andrew J.},
title = {Characterization of the Effects of Salicylidene Acylhydrazide Compounds
on Type III Secretion in Escherichia coli O157:H7},
journal = {Infect. Immun.},
year = {2009},
volume = {77},
pages = {4209--4220},
number = {10},
month = oct,
abstract = {Recent work has highlighted a number of compounds that target bacterial
virulence by affecting gene regulation. In this work, we show that
small-molecule inhibitors affect the expression of the type III secretion
system (T3SS) of Escherichia coli O157:H7 in liquid culture and when
this bacterium is attached to bovine epithelial cells. Inhibition
of T3SS expression resulted in a reduction in the capacity of the
bacteria to form attaching and effacing lesions. Our results show
that there is marked variation in the abilities of four structurally
related compounds to inhibit the T3SS of a panel of isolates. Using
transcriptomics, we performed a comprehensive analysis of the conserved
and inhibitor-specific transcriptional responses to these four compounds.
These analyses of gene expression show that numerous virulence genes,
located on horizontally acquired DNA elements, are affected by the
compounds, but the number of genes significantly affected varied
markedly for the different compounds. Overall, we highlight the importance
of assessing the effect of such "antivirulence" agents on a range
of isolates and discuss the possible mechanisms which may lead to
the coordinate downregulation of horizontally acquired virulence
genes.},
url = {http://iai.asm.org/cgi/content/abstract/77/10/4209}
}
@ARTICLE{TrehanPati2009,
author = {TrehanPati, Nirupma and Geffers, Robert and Sukriti and Hissar, Syed
and Riese, Peggy and Toepfer, Tanja and Buer, Jan and Kumar, Manoj
and Guzman, Carlos A. and Sarin, Shiv Kumar},
title = {Gene expression signatures of peripheral CD4+ T cells clearly discriminate
between patients with acute and chronic hepatitis B infection},
journal = {Hepatology},
year = {2009},
volume = {49},
pages = {781--790},
number = {3},
abstract = {Abstract 10.1002/hep.22696.abs CD4+ T and regulatory T cells (Tregs)
seem to play a key role in persistence of hepatitis B virus (HBV)
infection. However, the molecular events by which Tregs exert their
modulatory activity are largely unknown. The transcriptional profiles
of CD4+ T cells of healthy controls (HCs) and patients affected by
acute hepatitis B (AVH-B) or chronic hepatitis B (CHB) infection
were established using a custom expression array consisting of 350
genes relevant for CD4+ T cell and Treg function. These studies were
complemented by real-time reverse-transcription polymerase chain
reaction. Peripheral blood mononuclear cells (PBMCs) were also analyzed
for the presence of Tregs, which were more abundant in the acute
stage of the disease (7%) than in HCs and CHB infection (HCs versus
AVH-B, P = 0.003; AVH-B versus CHB, P = 0.04). One hundred eighteen
genes (34%) intrinsically differentiate HBV-infected patients from
HCs. Using gene ontology, we identified T cell receptor signaling
and clusterization, mitogen-activated protein kinase kinase signaling,
cell adhesion, cytokines and inflammatory responses, cell cycle/cell
proliferation, and apoptosis as the most prominent affected modules.
A higher expression of CCR1, CCR3, CCR4, CCR5, and CCR8 was seen
in AVH-B than in CHB-infected patients and HCs. Annotation of the
interconnected functional network of genes provided a unique representation
of global immune activation during acute infection. Almost all genes
were down-regulated in patients with CHB infection. Conclusion: The
fingerprints enable clear discrimination between patients suffering
from AVH-B or CHB infection. The observed profiles suggest accumulation
of effector T cells with a potential role in necro-inflammation during
the acute stage. Subsequent down-regulated effector functions support
the hypothesis of suppressed CD4+ effector T cells favoring viral
persistence in the chronic infection stage. (HEPATOLOGY 2009.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.22696}
}
@ARTICLE{Treister2005,
author = {Treister, N.S. and Richards, S.M. and Lombardi, M.J. and Rowley,
P. and Jensen, R.V. and Sullivan, D.A.},
title = {Sex-related Differences in Gene Expression in Salivary Glands of
BALB/c Mice},
journal = {Journal of Dental Research},
year = {2005},
volume = {84},
pages = {160--165},
number = {2},
month = feb,
abstract = {Sex-related differences exist in the structure and function of the
major glands in a variety of species. Moreover, many of these variations
appear to be unique to each tissue. We hypothesized that this sexual
dimorphism is due, at least in part, to gland-specific differences
in gene expression between males and females. Glands were collected
from male and female BALB/c mice (n = 5/sex/experiment), and total
RNA was isolated. Samples were analyzed for differentially expressed
mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter.
Our results demonstrate that significant (P < 0.05) sex-related differences
exist in the expression of numerous genes in the major salivary glands,
and many of these differences were tissue-specific. These findings
support our hypothesis that sex-related differences in the salivary
glands are due, at least in part, to tissue-specific variations in
gene expression.},
url = {http://jdr.sagepub.com/cgi/content/abstract/84/2/160}
}
@ARTICLE{Tremblay2011,
author = {Tremblay, Andre J. and Lamarche, Benoit and Lemelin, Valery and Hoos,
Lizbeth and Benjannet, Suzanne and Seidah, Nabil G. and Davis, Harry
R., Jr. and Couture, Patrick},
title = {Atorvastatin increases intestinal expression of NPC1L1 in hyperlipidemic
men},
journal = {J. Lipid Res.},
year = {2011},
volume = {52},
pages = {558--565},
number = {3},
month = mar,
abstract = {Inhibition of cholesterol synthesis by 3-hydroxy-3-methylglutaryl-CoA
reductase (HMG-CoAR) inhibitors has been associated with an increase
in intestinal cholesterol absorption. This study examined how HMG-CoAR
inhibition by atorvastatin modulates expression of key genes involved
in intestinal cholesterol metabolism. A crossover study was conducted
in which 22 hyperlipidemic men received atorvastatin, 40 mg/day,
or placebo, each for 12 weeks. Gene expression was assessed by real-time
PCR using duodenal biopsy samples obtained at the end of each phase
of treatment. Treatment with atorvastatin was associated with a 76%
reduction in lathosterol and significant increases in sitosterol
(70%). Atorvastatin significantly increased intestinal mRNA levels
of HMG-CoAR (59%), LDL receptor (LDLR) (52%), PCSK9 (187%), SREBP-2
(44%), and HNF-4[α] (13%). Furthermore, atorvastatin significantly
increased intestinal mRNA levels of NPC1L1 by 19% and decreased mRNA
levels of both ABCG5 and ABCG8 by 14%. Positive correlations were
observed between changes in SREBP-2 and HNF-4[α] expression
and concurrent changes in the intestinal mRNA levels of HMG-CoAR,
LDLR, and NPC1L1. These results indicate that HMG-CoAR inhibition
with atorvastatin stimulates the intestinal expression of NPC1L1,
LDLR, and PCSK9; increases cholesterol absorption; and reduces expression
of ABCG5/8; these effects are most likely mediated by upregulation
of the transcription factors SREBP-2 and HNF-4[α].},
comment = {10.1194/jlr.M011080},
url = {http://www.jlr.org/cgi/content/abstract/52/3/558}
}
@ARTICLE{Tremblay2010,
author = {Tremblay, Julien and Deziel, Eric},
title = {Gene expression in Pseudomonas aeruginosa swarming motility},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {587},
number = {1},
abstract = {BACKGROUND:The bacterium Pseudomonas aeruginosa is capable of three
types of motilities: swimming, twitching and swarming. The latter
is characterized by a fast and coordinated group movement over a
semi-solid surface resulting from intercellular interactions and
morphological differentiation. A striking feature of swarming motility
is the complex fractal-like patterns displayed by migrating bacteria
while they move away from their inoculation point. This type of group
behaviour is still poorly understood and its characterization provides
important information on bacterial structured communities such as
biofilms. Using GeneChip(R) Affymetrix microarrays, we obtained the
transcriptomic profiles of both bacterial populations located at
the tip of migrating tendrils and swarm center of swarming colonies
and compared these profiles to that of a bacterial control population
grown on the same media but solidified to not allow swarming motility.RESULTS:Microarray
raw data were corrected for background noise with the RMA algorithm
and quantile normalized. Differentially expressed genes between the
three conditions were selected using a threshold of 1.5 log2-fold,
which gave a total of 378 selected genes (6.3% of the predicted open
reading frames of strain PA14). Major shifts in gene expression patterns
are observed in each growth conditions, highlighting the presence
of distinct bacterial subpopulations within a swarming colony (tendril
tips vs. swarm center). Unexpectedly, microarrays expression data
reveal that a minority of genes are up-regulated in tendril tip populations.
Among them, we found energy metabolism, ribosomal protein and transport
of small molecules related genes. On the other hand, many well-known
virulence factors genes were globally repressed in tendril tip cells.
Swarm center cells are distinct and appear to be under oxidative
and copper stress responses.CONCLUSIONS:Results reported in this
study show that, as opposed to swarm center cells, tendril tip populations
of a swarming colony displays general down-regulation of genes associated
with virulence and up-regulation of genes involved in energy metabolism.
These results allow us to propose a model where tendril tip cells
function as "scouts" whose main purpose is to rapidly spread on uncolonized
surfaces while swarm center population are in a state allowing a
permanent settlement of the colonized area (biofilm-like).},
doi = {10.1186/1471-2164-11-587},
issn = {1471-2164},
pubmedid = {20961425},
url = {http://www.biomedcentral.com/1471-2164/11/587}
}
@ARTICLE{Trenerry2007,
author = {Trenerry, Marissa K. and Carey, Kate A. and Ward, Alister C. and
Cameron-Smith, David},
title = {STAT3 signaling is activated in human skeletal muscle following acute
resistance exercise},
journal = {J Appl Physiol},
year = {2007},
volume = {102},
pages = {1483--1489},
number = {4},
month = apr,
abstract = {The transcription factor signal transducer and activator of transcription
3 (STAT3) has been identified as a mediator of cytokine signaling
and implicated in hypertrophy; however, the importance of this pathway
following resistance exercise in human skeletal muscle has not been
investigated. In the present study, the phosphorylation and nuclear
localization of STAT3, together with STAT3-regulated genes, were
measured in the early recovery period following intense resistance
exercise. Muscle biopsy samples from healthy subjects (7 males, 23.0
+ 0.9 yr) were harvested before and again at 2, 4, and 24 h into
recovery following a single bout of maximal leg extension exercise
(3 sets, 12 repetitions). Rapid and transient activation of phosphorylated
(tyrosine 705) STAT3 was observed at 2 h postexercise. STAT3 phosphorylation
paralleled the transient localization of STAT3 to the nucleus, which
also peaked at 2 h postexercise. Downstream transcriptional events
regulated by STAT3 activation peaked at 2 h postexercise, including
early responsive genes c-FOS (800-fold), JUNB (38-fold), and c-MYC
(140-fold) at 2 h postexercise. A delayed peak in VEGF (4-fold) was
measured 4 h postexercise. Finally, genes associated with modulating
STAT3 signaling were also increased following exercise, including
the negative regulator SOCS3 (60-fold). Thus, following a single
bout of intense resistance exercise, a rapid phosphorylation and
nuclear translocation of STAT3 are evident in human skeletal muscle.
These data suggest that STAT3 signaling is an important common element
and may contribute to the remodeling and adaptation of skeletal muscle
following resistance exercise.},
url = {http://jap.physiology.org/cgi/content/abstract/102/4/1483}
}
@ARTICLE{Trent2006,
author = {Trent, Jonathan C. and Ramdas, Latha and Dupart, Jheri and Hunt,
Kelly and Macapinlac, Homer and Taylor, Ellen and Hu, Limei and Salvado,
August and Abbruzzese, James L. and Pollock, Raphael and Benjamin,
Robert S. and Zhang, Wei},
title = {Early effects of imatinib mesylate on the expression of insulin-like
growth factor binding protein-3 and positron emission tomography
in patients with gastrointestinal stromal tumor},
journal = {Cancer},
year = {2006},
volume = {107},
pages = {1898--1908},
number = {8},
abstract = {Abstract 10.1002/cncr.22214.abs BACKGROUND. Imatinib has demonstrated
marked clinical efficacy against gastrointestinal stromal tumor (GIST).
Microarray technology, real-time polymerase chain reaction (PCR)
validation, and fluorodeoxyglucose-positron emission tomography (FDG-PET)
imaging were used to study the early molecular effects of imatinib
antitumor activity in GIST. METHODS. After exposure of sensitive
and resistant sarcoma cell lines to imatinib for 24 to 48 hours,
the changes in gene expression were evaluated using a 1146 unique
pathway array with Western blot validation. Real-time PCR was used
to confirm changes in gene expression in human GIST samples (preimatinib
biopsy and postimatinib surgical specimen after 3–7 days of therapy).
FDG-PET was performed to correlate radiographic findings with the
effects of imatinib on gene expression in GIST. RESULTS. In all,
55 genes demonstrated a ≥ 2-fold change after imatinib treatment
of the GIST882 cells. Among these genes there was up-regulation of
insulin-like growth factor binding protein-3 (IGFBP-3), a protein
that modulates proliferation and apoptosis. Western blot analysis
confirmed the increase of IGFBP-3 only in imatinib-sensitive GIST882
cells. Up to a 7-fold induction (49% mean increase; P = .08) of IGFBP-3
mRNA was found in tumor samples from patients with low residual FDG
uptake, whereas there was an up to 12-fold reduction (−102% mean
decrease; P = .03) in IGFBP-3 in those patients with high residual
FDG uptake after imatinib therapy. CONCLUSIONS. In the current study,
imatinib appears to regulate numerous genes and specifically induces
IGFBP-3 in GIST cells and tumor samples. IGFBP-3 levels also were
found to be inversely correlated with residual FDG uptake in GIST
patients early in imatinib therapy. These initial observations suggest
that IGFBP-3 is an important early marker of antitumor activity of
imatinib in GIST. Cancer 2006. © 2006 American Cancer Society.},
issn = {1097-0142},
keywords = {gastrointestinal stromal tumor, gene expression, imatinib mesylate,
insulin-like growth factor binding protein-3, positron emission tomography},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cncr.22214}
}
@ARTICLE{Trentin2009,
author = {Trentin, Luca and Giordan, Marco and Dingermann, Theo and Basso,
Giuseppe and Te Kronnie, Geertruy and Marschalek, Rolf},
title = {Two independent gene signatures in pediatric t(4;11) acute lymphoblastic
leukemia patients},
journal = {European Journal of Haematology},
year = {2009},
volume = {83},
pages = {406--419},
number = {5},
abstract = {Abstract Objective:  Gene expression profiles become increasingly
more important for diagnostic procedures, allowing clinical predictions
including treatment response and outcome. However, the establishment
of specific and robust gene signatures from microarray data sets
requires the analysis of large numbers of patients and the application
of complex biostatistical algorithms. Especially in case of rare
diseases and due to these constrains, diagnostic centers with limited
access to patients or bioinformatic resources are excluded from implementing
these new technologies. Method:  In our study we sought to overcome
these limitations and for proof of principle, we analyzed the rare
t(4;11) leukemia disease entity. First, gene expression data of each
t(4;11) leukemia patient were normalized by pairwise subtraction
against normal bone marrow (n = 3) to identify significantly deregulated
gene sets for each patient. Result:  A ‘core signature’ of
186 commonly deregulated genes present in each investigated t(4;11)
leukemia patient was defined. Linking the obtained gene sets to four
biological discriminators (HOXA gene expression, age at diagnosis,
fusion gene transcripts and chromosomal breakpoints) divided patients
into two distinct subgroups: the first one comprised infant patients
with low HOXA genes expression and the MLL breakpoints within introns
11/12. The second one comprised non-infant patients with high HOXA
expression and MLL breakpoints within introns 9/10. Conclusion: 
A yet homogeneous leukemia entity was further subdivided, based on
distinct genetic properties. This approach provided a simplified
way to obtain robust and disease-specific gene signatures even in
smaller cohorts.},
issn = {1600-0609},
keywords = {acute leukemia, gene expression profiles, t(4;11), MLL gene, AF4 gene},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0609.2009.01305.x}
}
@ARTICLE{Tretiakova2010,
author = {Tretiakova, Maria S and Shabani-Rad, Meer T and Guggisberg, Kelly
and Hart, John and Anders, Robert A and Gao, Zu-hua},
title = {Genomic and immunophenotypical differences between hepatocellular
carcinoma with and without cirrhosis},
journal = {Histopathology},
year = {2010},
volume = {56},
pages = {683--693},
number = {6},
abstract = {Tretiakova M S, Shabani-Rad M T, Guggisberg K, Hart J, Anders R A
& Gao Z-h (2010) Histopathology 56, 683–693 Genomic and immunophenotypical
differences between hepatocellular carcinoma with and without cirrhosis
Aims:  To compare the expression of genes involved in p53, Wnt/β-catenin,
and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular
carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic
liver (HCC-NC). Methods and results:  The gene expression profile
was analysed using oligo-DNA arrays, and then validated at protein
level in a tissue microarray using immunohistochemistry. Compared
with their background non-neoplastic liver tissue, HCC-C showed a
significantly higher rate of p53, β-catenin (protein only) and cyclin
D1 expression, whereas HCC-NC showed a significantly higher rate
of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly
higher rate of p53 expression and a significantly lower rate of p21waf1/cip1
expression than HCC-NC. There was no statistically significant association
between the expression of genetic markers and tumour histological
grade, underlying aetiology, or lymphovascular invasion. Aberrant
β-catenin expression was more commonly seen in single tumours in
comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1
expression was more commonly observed in large-sized tumours (>50Â mm)
than small-sized tumours. Conclusions:  Alteration of the p53 pathway
plays a more important role in the pathogenesis of HCC-C, whereas
alterations in cell cycle regulators p21waf1/cip1 and p27Kip1 play
a more important role in the pathogenesis of HCC-NC.},
issn = {1365-2559},
keywords = {carcinogenesis, cirrhosis, gene profiling, hepatocellular carcinoma,
tissue microarray},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2559.2010.03554.x}
}
@ARTICLE{Trevaskis2005,
author = {Trevaskis, James and Walder, Ken and Foletta, Victoria and Kerr-Bayles,
Lyndal and McMillan, Janine and Cooper, Adrian and Lee, Scott and
Bolton, Kristy and Prior, Matthew and Fahey, Richard and Whitecross,
Kate and Morton, Gregory J. and Schwartz, Michael W. and Collier,
Greg R.},
title = {Src Homology 3-Domain Growth Factor Receptor-Bound 2-Like (Endophilin)
Interacting Protein 1, a Novel Neuronal Protein that Regulates Energy
Balance},
journal = {Endocrinology},
year = {2005},
volume = {146},
pages = {3757--3764},
number = {9},
month = sep,
abstract = {To identify genes involved in the central regulation of energy balance,
we compared hypothalamic mRNA from lean and obese Psammomys obesus,
a polygenic model of obesity, using differential display PCR. One
mRNA transcript was observed to be elevated in obese, and obese diabetic,
P. obesus compared with lean animals and was subsequently found to
be increased 4-fold in the hypothalamus of lethal yellow agouti (Ay/a)
mice, a murine model of obesity and diabetes. Intracerebroventricular
infusion of antisense oligonucleotide targeted to this transcript
selectively suppressed its hypothalamic mRNA levels and resulted
in loss of body weight in both P. obesus and Sprague Dawley rats.
Reductions in body weight were mediated by profoundly reduced food
intake without a concomitant reduction in metabolic rate. Yeast two-hybrid
screening, and confirmation in mammalian cells by bioluminescence
resonance energy transfer analysis, demonstrated that the protein
it encodes interacts with endophilins, mediators of synaptic vesicle
recycling and receptor endocytosis in the brain. We therefore named
this transcript Src homology 3-domain growth factor receptor-bound
2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes
a large proline-rich protein that is expressed predominantly in the
brain and is highly conserved between species. Together these data
suggest that SGIP1 is an important and novel member of the group
of neuronal molecules required for the regulation of energy homeostasis.},
url = {http://endo.endojournals.org/cgi/content/abstract/146/9/3757}
}
@ARTICLE{Trevino2010,
author = {Trevino, Jeanette and Perez, Nataly and Sumby, Paul},
title = {The 4.5S RNA component of the signal recognition particle is required
for group A Streptococcus virulence},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {1342--1350},
number = {5},
month = may,
abstract = {The signal recognition particle (SRP) is a ribonucleoprotein complex
that targets proteins for secretion in a co-translational manner.
While originally thought to be essential in all bacteria, recent
data show that the SRP is dispensable in at least some streptococcal
species. The SRP from the human pathogen group A Streptococcus (GAS,
Streptococcus pyogenes) is predicted to be composed of protein Ffh
and 4.5S RNA. Deletion of ffh alters the secretion of several GAS
proteins, and leads to a severe reduction in virulence. Here, we
report that mutation of the gene encoding 4.5S RNA results in phenotypes
both similar to and distinct from that observed following ffh mutation.
Similarities include a reduction in secretion of the haemolysin streptolysin
O, and attenuation of virulence as assessed by a murine soft tissue
infection model. Differences include a reduction in transcript levels
for the genes encoding streptolysin O and NAD-glycohydrolase, and
the reduced secretion of the SpeB protease. Several differences in
transcript abundance between the parental and mutant strain were
shown to be dependent on the sensor-kinase-encoding gene covS. Using
growth in human saliva as an ex vivo model of upper respiratory tract
infection we identified that 4.5S RNA mutation leads to a 10-fold
reduction in colony-forming units over time, consistent with the
4.5S RNA contributing to GAS growth and persistence during upper
respiratory tract infections. Finally, we determined that the 4.5S
RNA was essential for GAS to cause lethal infections in a murine
bacteraemia model of infection. The data presented extend our knowledge
of the contribution of the SRP to the virulence of an important Gram-positive
pathogen.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/5/1342}
}
@ARTICLE{Trevino2009,
author = {Trevino, Lindsey S. and Wang, Wei and Urick, Mary Ellen and Johnson,
Patricia A.},
title = {Global Gene Expression Analysis in Ovarian Cancer of the Hen.},
journal = {Biol Reprod},
year = {2009},
volume = {81},
pages = {535--},
number = {1_MeetingAbstracts},
month = jul,
url = {http://www.biolreprod.org}
}
@ARTICLE{Tribulatti2007,
author = {Tribulatti, Maria Virginia and Mucci, Juan and Cattaneo, Valentina
and Aguero, Fernan and Gilmartin, Tim and Head, Steven R. and Campetella,
Oscar},
title = {Galectin-8 Induces Apoptosis in the CD4highCD8high Thymocyte Subpopulation},
journal = {Glycobiology},
year = {2007},
volume = {17},
pages = {1404--1412},
number = {12},
month = dec,
abstract = {In the present work, we followed a microarray approach to analyze
the expression of glycosylation-related genes on different cell populations
obtained from mouse thymus. Among other genes, transcription of the
two-domain type galectin-8 was detected both in thymocytes and thymic
epithelial cells (TECs), which was confirmed by reverse transcriptase
(RT)-PCR assays independently carried out on both cell populations.
Two splice variants, differing solely in the presence of a nine amino
acid insertion in the linker peptide region connecting the two carbohydrate
recognition domains (CRDs), were identified from purified thymocytes.
Expression of galectin-8 was verified at the protein level in total
organ extracts by western-blots of lactosyl-Sepharose purified binders.
To explore the possible biological roles of locally produced galectin-8,
both splice variants were recombinantly expressed in bacteria and
assayed over cultured thymocytes. In spite of their binding to all
cell populations, addition of either isoform of galectin-8 to thymocyte
cultures induced apoptosis only of the CD4highCD8high cells through
caspases pathway activation. All of these effects were prevented
by the addition of thiodigalactoside (TDG) or lactose, thus indicating
that the proapoptotic activity of galectin-8 was due to the specific
interaction of its CRDs with defined cell surface glycans. Together,
our results demonstrate intrathymic expression of galectin-8 in mouse,
and suggest an active role for this lectin in shaping the mature
T cell repertoire.},
url = {http://glycob.oxfordjournals.org/cgi/content/abstract/17/12/1404}
}
@ARTICLE{Tricarico2002,
author = {Tricarico, Carmela and Pinzani, Pamela and Bianchi, Simonetta and
Paglierani, Milena and Distante, Vito and Pazzagli, Mario and Bustin,
Stephen A. and Orlando, Claudio},
title = {Quantitative real-time reverse transcription polymerase chain reaction:
normalization to rRNA or single housekeeping genes is inappropriate
for human tissue biopsies},
journal = {Analytical Biochemistry},
year = {2002},
volume = {309},
pages = {293--300},
number = {2},
month = oct,
issn = {0003-2697},
url = {http://www.sciencedirect.com/science/article/B6W9V-470TXY4-G/2/be315e29297edf6e84115f9d20bc1b6d}
}
@ARTICLE{Trick2009,
author = {Trick, Martin and Cheung, Foo and Drou, Nizar and Fraser, Fiona and
Lobenhofer, Edward and Hurban, Patrick and Magusin, Andreas and Town,
Christopher and Bancroft, Ian},
title = {A newly-developed community microarray resource for transcriptome
profiling in Brassica species enables the confirmation of Brassica-specific
expressed sequences},
journal = {BMC Plant Biology},
year = {2009},
volume = {9},
pages = {50},
number = {1},
abstract = {BACKGROUND:The Brassica species include an important group of crops
and provide opportunities for studying the evolutionary consequences
of polyploidy. They are related to Arabidopsis thaliana, for which
the first complete plant genome sequence was obtained and their genomes
show extensive, although imperfect, conserved synteny with that of
A. thaliana. A large number of EST sequences, derived from a range
of different Brassica species, are available in the public database,
but no public microarray resource has so far been developed for these
species.RESULTS:We assembled unigenes using ~800,000 EST sequences,
mainly from three species: B. napus, B. rapa and B. oleracea. The
assembly was conducted with the aim of co-assembling ESTs of orthologous
genes (including homoeologous pairs of genes in B. napus from each
of the A and C genomes), but resolving assemblies of paralogous,
or paleo-homoeologous, genes (i.e. the genes related by the ancestral
genome triplication observed in diploid Brassica species). 90,864
unique sequence assemblies were developed. These were incorporated
into the BAC sequence annotation for the Brassica rapa Genome Sequencing
Project, enabling the identification of cognate genomic sequences
for a proportion of them. A 60-mer oligo microarray comprising 94,558
probes was developed using the unigene sequences. Gene expression
was analysed in reciprocal resynthesised B. napus lines and the B.
oleracea and B. rapa lines used to produce them. The analysis showed
that significant expression could consistently be detected in leaf
tissue for 35,386 unigenes. Expression was detected across all four
genotypes for 27,355 unigenes, genome-specific expression patterns
were observed for 7,851 unigenes and 180 unigenes displayed other
classes of expression pattern. Principal component analysis (PCA)
clearly resolved the individual microarray datasets for B. rapa,
B. oleracea and resynthesised B. napus. Quantitative differences
in expression were observed between the resynthesised B. napus lines
for 98 unigenes, most of which could be classified into non-additive
expression patterns, including 17 that showed cytoplasm-specific
patterns. We further characterized the unigenes for which A genome-specific
expression was observed and cognate genomic sequences could be identified.
Ten of these unigenes were found to be Brassica-specific sequences,
including two that originate from complex loci comprising gene clusters.CONCLUSION:We
succeeded in developing a Brassica community microarray resource.
Although expression can be measured for the majority of unigenes
across species, there were numerous probes that reported in a genome-specific
manner. We anticipate that some proportion of these will represent
species-specific transcripts and the remainder will be the consequence
of variation of sequences within the regions represented by the array
probes. Our studies demonstrated that the datasets obtained from
the arrays can be used for typical analyses, including PCA and the
analysis of differential expression. We have also demonstrated that
Brassica-specific transcripts identified in silico in the sequence
assembly of public EST database accessions are indeed reported by
the array. These would not be detectable using arrays designed using
A. thaliana sequences.},
doi = {10.1186/1471-2229-9-50},
issn = {1471-2229},
pubmedid = {19426481},
url = {http://www.biomedcentral.com/1471-2229/9/50}
}
@ARTICLE{Triebel2009,
author = {Triebel, Jakob and Huefner, Michael and Ramadori, Giuliano},
title = {Investigation of prolactin-related vasoinhibin in sera from patients
with diabetic retinopathy},
journal = {Eur. J. Endocrinol.},
year = {2009},
volume = {161},
pages = {345--353},
number = {2},
month = aug,
abstract = {ObjectiveIn vitro experiments and in vivo studies on rodents demonstrate
that N-terminal 14, 15, 16, 17, and 18 kDa fragments prolactin-related
vasoinhibin (PRL-V) of human PRL are natural inhibitors of neovascularization
in the retina and elsewhere. These N-terminal PRL fragments belong
to a family of peptides named vasoinhibins, which act as endogenous
regulators of angiogenesis and vascular function. These observations
led to the hypothesis that PRL-V could play a role in the pathophysiology
of diabetic retinopathy in humans. The purpose of this study was
to investigate whether patients with diabetes mellitus and diabetic
retinopathy have aberrant concentrations of PRL-V in the circulating
blood. Research designWe performed a case-control study and developed
a new technique to semi-quantitatively determine PRL-V in serum samples
from 48 male subjects. The case group consisted of 21 patients with
diabetes mellitus and proliferative or non-proliferative diabetic
retinopathy. The control group consisted of 27 healthy subjects with
no history of diabetes mellitus. MethodsFor the detection of PRL-V,
we developed a new analytical method, consisting of immunologic and
laser-induced fluorescence techniques. ResultsThe case group had
significantly lower PRL-V serum concentrations than the control group
(P=0.041). There was no significant difference between patients with
proliferative and those with non-proliferative diabetic retinopathy.
ConclusionWe conclude that given the antiangiogenic and antivasopermeability
actions of PRL-V, the decreased serum levels of PRL-V in patients
with diabetes mellitus could contribute to the development and progression
of diabetic retinopathy.},
url = {http://www.eje-online.org/cgi/content/abstract/161/2/345}
}
@ARTICLE{Trietsch2011,
author = {S.J. Trietsch and T. Hankemeier and H.J. van der Linden},
title = {Lab-on-a-chip technologies for massive parallel data generation in
the life sciences: A review},
journal = {Chemometrics and Intelligent Laboratory Systems},
year = {2011},
volume = {108},
pages = {64 - 75},
number = {1},
note = {Analytical Platforms for Providing and Handling Massive
Chemical Data},
abstract = {Lab-on-a-chip (LOC) technology is an important and rapidly developing
research field focused on improving experimentation and analysis
in the life sciences through miniaturization of full analytical systems
into (monolithic) chip substrates. Since its emergence in the 1970s
[1], the field has matured, gaining tremendous momentum in the last
two decades. Miniaturization and integration of analytical processes
on a chip can offer enormous advantages over existing technologies
and can create a range of novel opportunities in the life sciences.
The developments in the field have led to significant increases in
analysis throughput, more than billion-fold sample volume reductions
and increased separation efficiency. Despite its potential for the
life sciences, the existence and the implications of LOCs are not
widely known outside its community.
The aim of this review is to introduce scientists from different disciplines
to LOC technology. We will discuss the most important LOCs, their
physical operating principles and the unique benefits that can be
gained through miniaturization. We will conclude this review with
a discussion of the potential of LOCs for massive parallel data generation
and their potential implications for the life sciences.},
doi = {10.1016/j.chemolab.2011.03.005},
issn = {0169-7439},
keywords = {Micro total analysis systems},
url = {http://www.sciencedirect.com/science/article/pii/S0169743911000554}
}
@ARTICLE{Trimarco2008,
author = {Trimarco, Amelia and Torella, Annalaura and Piluso, Giulio and Maria
Ventriglia, Vega and Politano, Luisa and Nigro, Vincenzo},
title = {Log-PCR: A New Tool for Immediate and Cost-Effective Diagnosis of
up to 85% of Dystrophin Gene Mutations},
journal = {Clin. Chem.},
year = {2008},
volume = {54},
pages = {973--981},
number = {6},
month = jun,
abstract = {Background: Duchenne (DMD) and Becker (BMD) muscular dystrophies are
caused by mutations in the dystrophin gene. Despite the progress
in the technologies of mutation detection, the disease of one third
of patients escapes molecular definition because the labor and expense
involved has precluded analyzing the entire gene. Novel techniques
with higher detection rates, such as multiplex ligation-dependent
probe amplification and multiplex amplifiable probe hybridization,
have been introduced. Methods: We approached the challenge of multiplexing
by modifying the PCR chemistry. We set up a rapid protocol that analyzes
all dystrophin exons and flanking introns (57.5 kb). We grouped exons
according to their effect on the reading frame and ran 2 PCR reactions
for DMD mutations and 2 reactions for BMD mutations under the same
conditions. The PCR products are evenly spaced logarithmically on
the gel (Log-PCR) in an order that reproduces their chromosomal locations.
This strategy enables both simultaneous mapping of all the mutation
borders and distinguishing between DMD and BMD. As a proof of principle,
we reexamined samples from 506 patients who had received a DMD or
BMD diagnosis. Results: We observed gross rearrangements in 428 of
the patients (84.6%; 74.5% deletions and 10.1% duplications). We
also recognized a much broader spectrum of mutations and identified
14.6% additional cases. Conclusions: This study is the first exhaustive
investigation of this subject and has made possible the development
of a cost-effective test for diagnosing a larger proportion of cases.
The benefit of this approach may allow more focused efforts for discovering
small or deep-intronic mutations among the few remaining undiagnosed
cases. The same protocol can be extended to set up Log-PCRs for other
high-throughput applications.},
url = {http://www.clinchem.org/cgi/content/abstract/54/6/973}
}
@ARTICLE{Tringe2006,
author = {Tringe, Susannah Green and Willis, Jason and Liberatore, Katie L.
and Ruby, Stephanie W.},
title = {The WTM Genes in Budding Yeast Amplify Expression of the Stress-Inducible
Gene RNR3},
journal = {Genetics},
year = {2006},
volume = {174},
pages = {1215--1228},
number = {3},
month = nov,
abstract = {Cellular responses to DNA damage and inhibited replication are evolutionarily
conserved sets of pathways that are critical to preserving genome
stability. To identify new participants in these responses, we undertook
a screen for regulators that, when present on a high-copy vector,
alter expression of a DNA damage-inducible RNR3-lacZ reporter construct
in Saccharomyces cerevisiae. From this screen we isolated a plasmid
encoding two closely related paralogs, WTM1 and WTM2, that greatly
increases constitutive expression of RNR3-lacZ. Moderate overexpression
of both genes together, or high-level expression of WTM2 alone from
a constitutive promoter, upregulates RNR3-lacZ in the absence of
DNA damage. Overexpressed, tagged Wtm2p is associated with the RNR3
promoter, indicating that this effect is likely direct. Further investigation
reveals that Wtm2p and Wtm1p, previously described as regulators
of meiotic gene expression and transcriptional silencing, amplify
transcriptional induction of RNR3 in response to replication stress
and modulate expression of genes encoding other RNR subunits.},
url = {http://www.genetics.org/cgi/content/abstract/174/3/1215}
}
@ARTICLE{Tripathi2012,
author = {Ajai K. Tripathi and Prakash G. Koringa and Subhash J. Jakhesara
and Viral B. Ahir and Umed V. Ramani and Vaibhav D. Bhatt and Manisha
R. Sajnani and Drashti A. Patel and Akash J. Joshi and Sundaram J.
Shanmuga and Dharamshi N. Rank and Chaitanya G. Joshi},
title = {A preliminary sketch of horn cancer transcriptome in Indian zebu
cattle},
journal = {Gene},
year = {2012},
volume = {493},
pages = {124 - 131},
number = {1},
abstract = {Horn cancer, a type of squamous cell carcinoma, in zebu cattle is
an expensive affair in Indian agriculture sector, which accounts
for 83.34% of total tumors found. In general, cancer tissue confirms
considerably different expression patterns when compared to a normal
stage. This includes not only up/down regulation, but also, the aberrant
gene expression, the presence of different non-coding RNAs (ncRNAs),
pseudogenes expression and genes involved in unusual pathways. We
employed Roche 454 next generation sequencing platform to sequence
Bos indicus cancerous and normal horn tissue transcripts. This resulted
into a total of 909,345 high-confidence deep sequencing reads and
detected a range of unusual transcriptional events including tumor
associated genes. We also validated expression of two of the four
tested genes in five other similar tissue samples by RT-qPCR. Further,
seven cancer specific non-coding transcripts were accessed and a
few of them have been suggested as cancer specific markers. This
study for the first time provides primary transcriptome sketch of
Bos indicus horn cancer tissue, and also demonstrates the suitability
of the 454 sequencer for transcriptome analysis, which supports the
concept of varied gene expression in cancerous condition.},
doi = {10.1016/j.gene.2011.11.007},
issn = {0378-1119},
keywords = {Transcriptome},
url = {http://www.sciencedirect.com/science/article/pii/S0378111911006639}
}
@ARTICLE{Tripathi2009,
author = {Tripathi, Abhai K. and Sha, Wei and Shulaev, Vladimir and Stins,
Monique F. and Sullivan, David J., Jr},
title = {Plasmodium falciparum-infected erythrocytes induce NF-{kappa}B regulated
inflammatory pathways in human cerebral endothelium},
journal = {Blood},
year = {2009},
volume = {114},
pages = {4243--4252},
number = {19},
month = nov,
abstract = {Cerebral malaria is a severe multifactorial condition associated with
the interaction of high numbers of infected erythrocytes to human
brain endothelium without invasion into the brain. The result is
coma and seizures with death in more than 20% of cases. Because the
brain endothelium is at the interface of these processes, we investigated
the global gene responses of human brain endothelium after the interaction
with Plasmodium falciparum-infected erythrocytes with either high-
or low-binding phenotypes. The most significantly up-regulated transcripts
were found in gene ontology groups comprising the immune response,
apoptosis and antiapoptosis, inflammatory response, cell-cell signaling,
and signal transduction and nuclear factor {kappa}B (NF-{kappa}B)
activation cascade. The proinflammatory NF-{kappa}B pathway was central
to the regulation of the P falciparum-modulated endothelium transcriptome.
The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2,
IL-6, and IL-8, were increased more than 100-fold, suggesting an
important role of blood-brain barrier (BBB) endothelium in the innate
defense during P falciparum-infected erythrocyte (Pf-IRBC) sequestration.
However, some of these diffusible molecules could have reversible
effects on brain tissue and thus on neurologic function. The inflammatory
pathways were validated by direct measurement of proteins in brain
endothelial supernatants. This study delineates the strong inflammatory
component of human brain endothelium contributing to cerebral malaria.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/19/4243}
}
@ARTICLE{Tripmacher2008,
author = {Tripmacher, Robert and Gaber, Timo and Dziurla, René and Häupl,
Thomas and Erekul, Kerem and Grützkau, Andreas and Tschirschmann,
Miriam and Scheffold, Alexander and Radbruch, Andreas and Burmester,
Gerd-Rüdiger and Buttgereit, Frank},
title = {Human CD4+ T cells maintain specific functions even under conditions
of extremely restricted ATP production},
journal = {Eur. J. Immunol.},
year = {2008},
volume = {38},
pages = {1631--1642},
number = {6},
abstract = {Abstract We investigated the energy-adaptive potential of human CD4+
T cells under conditions of impaired oxidative phosphorylation (OXPHOS)
and/or low glucose (inhibiting glycolysis). These cells often encounter
these conditions when executing their functions in injured/inflamed
tissues, even though T cells themselves require constant and adequate
energy supply via ATP. We assessed two specific functions, cytokine
synthesis and proliferation, and addressed whether adaptive characteristics
also emerged in vivo. In glucose-containing medium, both cytokine
production and proliferation were unaffected, even under complete
OXPHOS suppression. Only when glucose was also absent were these
functions significantly decreased. Partial recovery of OXPHOS and
induced glycolysis were crucial for the maintenance of cellular energy
supply. Adaptive regulatory mechanisms are clinically relevant because
hypoxia up-regulates glycolytic genes but down-regulates OXPHOS genes
in vivo. Our data demonstrate an unexpectedly high, clinically relevant
adaptive potential of human CD4+ T cells to maintain specific functions
even under severely impaired bioenergetic conditions. Supporting
Information for this article is available at www.wiley-vch.de/contents/jc_2040/200838047_s.pdf},
issn = {1521-4141},
keywords = {Cell activation, Cytokines, Oxidative phosphorylation, Rheumatoid
arthritis, T helper cells},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200738047}
}
@ARTICLE{Tripodi2009,
author = {Tripodi, Dominique and Quéméner, Sylvia and Renaudin, Karine and
Ferron, Christophe and Malard, Olivier and Guisle-Marsollier, Isabelle
and Sébille-Rivain, Véronique and Verger, Christian and Géraut, Christian
and Gratas-Rabbia-Ré, Catherine},
title = {Gene expression profiling in sinonasal adenocarcinoma},
journal = {BMC Medical Genomics},
year = {2009},
volume = {2},
pages = {65},
number = {1},
abstract = {BACKGROUND:Sinonasal adenocarcinomas are uncommon tumors which develop
in the ethmoid sinus after exposure to wood dust. Although the etiology
of these tumors is well defined, very little is known about their
molecular basis and no diagnostic tool exists for their early detection
in high-risk workers.METHODS:To identify genes involved in this disease,
we performed gene expression profiling using cancer-dedicated microarrays,
on nine matched samples of sinonasal adenocarcinomas and non-tumor
sinusal tissue. Microarray results were validated by quantitative
RT-PCR and immunohistochemistry on two additional sets of tumors.RESULTS:Among
the genes with significant differential expression we selected LGALS4,
ACS5, CLU, SRI and CCT5 for further exploration. The overexpression
of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed
by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4
(Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins:
LGALS4 was highly up-regulated, particularly in the most differentiated
tumors, while CLU was lost in all tumors. The expression of ACS5,
was more heterogeneous and no correlation was observed with the tumor
type.CONCLUSION:Within our microarray study in sinonasal adenocarcinoma
we identified two proteins, LGALS4 and CLU, that were significantly
differentially expressed in tumors compared to normal tissue. A further
evaluation on a new set of tissues, including precancerous stages
and low grade tumors, is necessary to evaluate the possibility of
using them as diagnostic markers.},
doi = {10.1186/1755-8794-2-65},
issn = {1755-8794},
pubmedid = {19903339},
url = {http://www.biomedcentral.com/1755-8794/2/65}
}
@ARTICLE{Tripp2011,
author = {Tripp, Adam and Kota, Rama S. and Lewis, David A. and Sibille, Etienne},
title = {Reduced somatostatin in subgenual anterior cingulate cortex in major
depression},
journal = {Neurobiology of Disease},
year = {2011},
volume = {42},
pages = {116--124},
number = {1},
month = apr,
abstract = {Converging evidence suggests a central role for dysfunction of the
subgenual anterior cingulate cortex (sgACC) in the pathophysiology
of major depressive disorder (MDD). Underlying mechanisms may include
altered GABAergic function. Expression of somatostatin (SST), an
inhibitory neuropeptide localized to a subset of GABA neurons, has
been shown to be lower in the dorsolateral prefrontal cortex of male
MDD subjects. Here, to investigate whether alterations in SST may
contribute to sgACC dysfunction in MDD, and whether the alterations
display sex-specificity, we measured sgACC SST at the mRNA and precursor
peptide levels in a large cohort of subjects with MDD. SST mRNA levels
were analyzed by quantitative PCR (qPCR) in the postmortem sgACC
from male (n = 26) and female (n = 25) subjects with MDD and sex-matched
subjects with no psychiatric diagnosis (n = 51). Prepro-SST protein
levels were assessed in a subset of subjects (n = 42 pairs) by semi-quantitative
Western blot. The mRNA expression of SST was significantly reduced
by 38% in female subjects and by 27% in male subjects with MDD. The
characteristic age-related decline in SST expression was observed
in control (Pearson R = - 0.357, p = 0.005) but not MDD (R = - 0.104,
p = 0.234) subjects, as low expression was detected across ages in
MDD subjects. Protein expression was similarly reduced by 19% in
both MDD groups, and findings were more robust in female (p = 0.0056)
than in males (p = 0.0373) compared to respective controls. In conclusion,
low SST represents a robust pathological finding in MDD. Specifically,
alterations in SST signaling and/or SST-bearing GABA neurons may
represent a critical pathophysiological entity that contributes to
sgACC dysfunction and that matches to the high female vulnerability
to develop MDD.},
issn = {0969-9961},
keywords = {Somatostatin, Major depression, Postmortem, Cingulate, Interneuron,
GABA, Male, Female, Age},
url = {http://www.sciencedirect.com/science/article/pii/S0969996111000155}
}
@ARTICLE{Trmcic2011,
author = {Trmcic, A. and Monnet, C. and Rogelj, I. and Bogovic Matijasic, B.},
title = {Expression of nisin genes in cheese--A quantitative real-time polymerase
chain reaction approach},
journal = {Journal of Dairy Science},
year = {2011},
volume = {94},
pages = {77--85},
number = {1},
month = jan,
abstract = {The role of bacteriocins in different environments has not been thoroughly
explained, mainly because of the difficulties related to the detection
of their production. Nisin, an antimicrobial peptide produced by
Lactococcus lactis has a long history of safe use in food products
and has been studied from many aspects of genetics, biosynthesis,
immunity, regulation, and mode of action. Still, some aspects concerning
the dynamics of nisin gene expression remain unknown, especially
in complex media like cheese. The main objective of the present study
was to quantify in a cheese-like medium the expression of nisin genes
in L. lactis M78, a well-characterized nisin A producer isolated
from raw milk. The expression of all 11 genes involved in nisin biosynthesis
was evaluated during cheese production by real-time reverse transcription-PCR.
Total RNA was extracted from cheeses using a direct extraction method
without prior separation of microbial cells. The M78 strain grew
well in experimental cheeses, producing detectable amounts of nisin
after 4 h of fermentation. The presence of nisin as an activator
modified both the expression of nisin genes and the accumulation
of active nisin. Four groups could be distinguished based on gene
expression as a function of time: nisA, nisFEG, nisRK and nisBTCIP.
Based on nisin-producing strain growth, nisin activity, function
of nisin genes, and their location, correlations were established
that contribute to the explanation of regulation of nisin biosynthesis
and immunity. This study is the first in which the evolution of bacteriocin
gene transcripts has been quantified rigorously in a cheese-like
medium.},
issn = {0022-0302},
keywords = {nisin, gene expression, real-time reverse transcription-polymerase
chain reaction, cheese},
url = {http://www.sciencedirect.com/science/article/pii/S0022030210006764}
}
@ARTICLE{Troadec2008,
author = {Troadec, Marie-Bérengère and Fautrel, Alain and Drénou, Bernard and
Leroyer, Patricia and Camberlein, Emilie and Turlin, Bruno and Guillouzo,
André and Brissot, Pierre and Loréal, Olivier},
title = {Transcripts of ceruloplasmin but not hepcidin, both major iron metabolism
genes, exhibit a decreasing pattern along the portocentral axis of
mouse liver},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
year = {2008},
volume = {1782},
pages = {239--249},
number = {4},
month = apr,
abstract = {Background/aims During iron overload of dietary origin, iron accumulates
predominantly in periportal hepatocytes. A gradient in the basal
and normal transcriptional control of genes involved in iron metabolism
along the portocentral axis of liver lobules could explain this feature.
Therefore, we aimed at characterizing, by quantitative RT-PCR, the
expression of iron metabolism genes in adult C57BL/6 mouse hepatocytes
regarding lobular localisation, with special emphasis to cell ploidy,
considering its possible relationship with lobular zonation.Methods
We used two methods to analyse separately periportal and perivenous
liver cells: 1) a selective liver zonal destruction by digitonin
prior to a classical collagenase dissociation, and 2) laser capture
microdissection. We also developed a method to separate viable 4N
and 8N polyploid hepatocytes by flow cytometer.Results Transcripts
of ceruloplasmin, involved in iron efflux, were overexpressed in
periportal areas and the result was confirmed by in situ hybridization
study. By contrast, hepcidin 1, hemojuvelin, ferroportin, transferrin
receptor 2, hfe and l-ferritin mRNAs were not differentially expressed
according to either lobular zonation or polyploidisation level.Conclusions
At variance with glutamine or urea metabolism, iron metabolism is
not featured by a metabolic zonation lying only on a basal transcriptional
control. The preferential periportal expression of ceruloplasmin
raises the issue of its special role in iron overload disorders involving
a defect in cellular iron export.},
issn = {0925-4439},
keywords = {Iron metabolism, Liver zonation, Ploidy, Ceruloplasmin, Hepcidin,
Gene expression, Laser microdissection, Cytometry, Mouse},
url = {http://www.sciencedirect.com/science/article/B6T1Y-4RH37VX-1/2/9aae58e4249925e8e245dfda85bbc442}
}
@ARTICLE{Troadec2006,
author = {Troadec, Marie-Bérengère and Glaise, Denise and Lamirault, Guillaume
and Le Cunff, Martine and Guérin, Emilie and Le Meur, Nolwenn and
Détivaud, Lénaïck and Zindy, Pierre and Leroyer, Patricia and Guisle,
Isabelle and Duval, Hélène and Gripon, Philippe and Théret, Nathalie
and Boudjema, Karim and Guguen-Guillouzo, Christiane and Brissot,
Pierre and Léger, Jean J. and Loréal, Olivier},
title = {Hepatocyte iron loading capacity is associated with differentiation
and repression of motility in the HepaRG cell line},
journal = {Genomics},
year = {2006},
volume = {87},
pages = {93--103},
number = {1},
month = jan,
abstract = {High liver iron content is a risk factor for developing hepatocellular
carcinoma (HCC). However, HCC cells are always iron-poor. Therefore,
an association between hepatocyte iron storage capacity and differentiation
is suggested. To characterize biological processes involved in iron
loading capacity, we used a cDNA microarray to study the differentiation
of the human HepaRG cell line, from undifferentiated proliferative
cells to hepatocyte differentiated cells. We were able to identify
genes modulated along HepaRG differentiation, leading us to propose
new genes not previously associated with HCC. Moreover, using Gene
Ontology annotations, we demonstrated that HepaRG hepatocyte iron
loading capacity occurred both with the repression of genes involved
in cell motility, signal transduction, and biosynthesis and with
the appearance of genes linked to lipid metabolism and immune response.
These results provide new insights in the understanding of the relationship
between iron and hepatocyte differentiation during iron-related hepatic
diseases.},
issn = {0888-7543},
keywords = {Hepatocyte, Iron metabolism disorders, Cell differentiation, Cell
cycle, Cell motility, Gene expression, cDNA microarrays, Microarray
analysis, Hepatocellular carcinoma},
url = {http://www.sciencedirect.com/science/article/B6WG1-4HPD3NG-1/2/d9aedab0073f49b9e105a9d985e5c1bc}
}
@ARTICLE{Trogan2006,
author = {Trogan, Eugene and Feig, Jonathan E. and Dogan, Snjezana and Rothblat,
George H. and Angeli, Veronique and Tacke, Frank and Randolph, Gwendalyn
J. and Fisher, Edward A.},
title = {Gene expression changes in foam cells and the role of chemokine receptor
CCR7 during atherosclerosis regression in ApoE-deficient mice},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {3781--3786},
number = {10},
month = mar,
abstract = {Atherosclerosis regression is an important clinical goal. In previous
studies of regression in mice, the rapid loss of plaque foam cells
was explained by emigration to lymph nodes, a process reminiscent
of dendritic cells. In the present study, plaque-containing arterial
segments from apoE-/- mice were transplanted into WT recipient normolipidemic
mice or apoE-/- mice. Three days after transplant, in the WT regression
environment, plaque size decreased by {approx}40%, and foam cell
content by {approx}75%. In contrast, both parameters increased in
apoE-/- recipients. Foam cells were isolated by laser capture microdissection.
In WT recipients, there were 3- to 6-fold increases in foam cells
of mRNA for liver X receptor {alpha} and cholesterol efflux factors
ABCA1 and SR-BI. Although liver X receptor {alpha} was induced, there
was no detectable expression of its putative activator, peroxisome
proliferator-activated receptor {gamma}. Expression levels of VCAM
or MCP-1 were reduced to 25% of levels in pretransplant or apoE-/-
recipient samples, but there was induction at the mRNA and protein
levels of chemokine receptor CCR7, an essential factor for dendritic
cell migration. Remarkably, when CCR7 function was abrogated in vivo
by treatment of WT recipients with antibodies to CCR7 ligands CCL19
and CCL21, lesion size and foam cell content were substantially preserved.
In summary, in foam cells during atherosclerosis regression, there
is induction of CCR7 and a requirement for its function. Taken with
the other gene expression data, these results in vivo point to complex
relationships among the immune system, nuclear hormone receptors,
and inflammation during regression.},
url = {http://www.pnas.org/cgi/content/abstract/103/10/3781}
}
@ARTICLE{Trollmann2010,
author = {Trollmann, Regina and Rehrauer, Hubert and Schneider, Christina and
Krischke, Gudrun and Huemmler, Nicolas and Keller, Stephan and Rascher,
Wolfgang and Gassmann, Max},
title = {Late-gestational systemic hypoxia leads to a similar early gene response
in mouse placenta and developing brain},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2010},
volume = {299},
pages = {R1489--1499},
number = {6},
month = dec,
abstract = {Late-gestational intrauterine hypoxia represents a well-known risk
factor of acquired perinatal brain injury. Cell type and age-specific
sensitivity of hypoxia-responsive genes to low-oxygen partial pressure
is to be considered in the screening for early indicators of fetoplacental
tissue hypoxia. To identify early hypoxia-induced alterations in
gene expression during late-gestational hypoxia (6% O2, 6 h; gestational
day 20) we compared primary mouse placenta and brain transcriptomes
using high-density oligonucleotide microarrays. Upregulation of candidate
marker genes for hypoxia was confirmed by quantitative RT-PCR and
immunohistochemistry. Both developing brain and placenta were highly
responsive to systemic hypoxia at the level of gene expression involving
hypoxia-inducible transcription factor (HIF)-dependent genes and
immediate early genes (IEG) (Fos, Jun, Egr1, Bhlhb2), apoptosis-promoting
factors (Bnip3, Dusp1, Ier3) that were all upregulated, and genes
modulating RNA binding and translation (Rbm3, Thap2, Lig4, Rbm12b)
that mainly were downregulated. Functional activity of the HIF system
was obvious from elevated expression of various known HIF target
genes (Adm, Vegf, Hk2, Pdk1, Bnip3, Ier3, Dusp-1), indicating immediate
availability among early response to acute hypoxia. In addition,
genes not yet described as being hypoxia related were identified
that are involved in angiogenesis/cell differentiation (Gna13, Gab2),
mRNA processing, and embryonic development. RT-PCR of placenta and
brain tissues confirmed upregulation of selected HIF target genes
and IEG. These data indicate that the early hypoxia-induced genomic
response of the placenta mirrors that of developing brain in a temporally
parallel manner. Our observations implicate future diagnostic options
to identify fetal and cerebral tissue hypoxia.},
comment = {10.1152/ajpregu.00697.2009},
url = {http://ajpregu.physiology.org/cgi/content/abstract/299/6/R1489}
}
@ARTICLE{Tronche2004,
author = {Tronche, Francois and Opherk, Christian and Moriggl, Richard and
Kellendonk, Christoph and Reimann, Andreas and Schwake, Lukas and
Reichardt, Holger M. and Stangl, Katharina and Gau, Daniel and Hoeflich,
Andreas and Beug, Hartmut and Schmid, Wolfgang and Schutz, Gunther},
title = {Glucocorticoid receptor function in hepatocytes is essential to promote
postnatal body growth},
journal = {Genes \& Dev.},
year = {2004},
volume = {18},
pages = {492--497},
number = {5},
month = mar,
abstract = {Mice carrying a hepatocyte-specific inactivation of the glucorticoid
receptor (GR) gene show a dramatic reduction in body size. Growth
hormone signaling mediated by the Stat5 transcription factors is
impaired. We show that Stat5 proteins physically interact with GR
and GR is present in vivo on Stat5-dependent IGF-I and ALS regulatory
regions. Interestingly, mice with a DNA-binding-deficient GR but
an unaltered ability to interact with STAT5 (GRdim/dim) have a normal
body size and normal levels of Stat5-dependent mRNAs. These findings
strongly support the model in which GR acts as a coactivator for
Stat5-dependent transcription upon GH stimulation and reveal an essential
role of hepatic GR in the control of body growth.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/18/5/492}
}
@ARTICLE{Troncoso-Ponce2011,
author = {Troncoso-Ponce, Manuel A. and Kilaru, Aruna and Cao, Xia and Durrett,
Timothy P. and Fan, Jilian and Jensen, Jacob K. and Thrower, Nick
A. and Pauly, Markus and Wilkerson, Curtis and Ohlrogge, John B.},
title = {Comparative deep transcriptional profiling of four developing oilseeds},
journal = {The Plant Journal},
year = {2011},
volume = {68},
pages = {1014--1027},
number = {6},
abstract = {Transcriptome analysis based on deep expressed sequence tag (EST)
sequencing allows quantitative comparisons of gene expression across
multiple species. Using pyrosequencing, we generated over 7 million
ESTs from four stages of developing seeds of Ricinus communis, Brassica
napus, Euonymus alatus and Tropaeolum majus, which differ in their
storage tissue for oil, their ability to photosynthesize and in the
structure and content of their triacylglycerols (TAG). The larger
number of ESTs in these 16 datasets provided reliable estimates of
the expression of acyltransferases and other enzymes expressed at
low levels. Analysis of EST levels from these oilseeds revealed both
conserved and distinct species-specific expression patterns for genes
involved in the synthesis of glycerolipids and their precursors.
Independent of the species and tissue type, ESTs for core fatty acid
synthesis enzymes maintained a conserved stoichiometry and a strong
correlation in temporal profiles throughout seed development. However,
ESTs associated with non-plastid enzymes of oil biosynthesis displayed
dissimilar temporal patterns indicative of different regulation.
The EST levels for several genes potentially involved in accumulation
of unusual TAG structures were distinct. Comparison of expression
of members from multi-gene families allowed the identification of
specific isoforms with conserved function in oil biosynthesis. In
all four oilseeds, ESTs for Rubisco were present, suggesting its
possible role in carbon metabolism, irrespective of light availability.
Together, these data provide a resource for use in comparative and
functional genomics of diverse oilseeds. Expression data for more
than 350 genes encoding enzymes and proteins involved in lipid metabolism
are available at the ‘ARALIP’ website (http://aralip.plantbiology.msu.edu/).},
doi = {10.1111/j.1365-313X.2011.04751.x},
issn = {1365-313X},
keywords = {lipid metabolism, triacylglycerol synthesis, fatty acid biosynthesis,
pyrosequencing, expressed sequence tags, comparative transcriptomics},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2011.04751.x}
}
@ARTICLE{Tronel2010,
author = {Tronel, Sophie and Belnoue, Laure and Grosjean, Noelle and Revest,
Jean-Michel and Piazza, Pier-Vincenzo and Koehl, Muriel and Abrous,
Djoher Nora},
title = {Adult-born neurons are necessary for extended contextual discrimination},
journal = {Hippocampus},
year = {2010},
pages = {n/a--n/a},
abstract = {Abstract New neurons are continuously produced in the adult dentate
gyrus of the hippocampus. It has been shown that one of the functions
of adult neurogenesis is to support spatial pattern separation, a
process that transforms similar memories into nonoverlapping representations.
This prompted us to investigate whether adult-born neurons are required
for discriminating two contexts, i.e., for identifying a familiar
environment and detect any changes introduced in it. We show that
depleting adult-born neurons impairs the animal's ability to disambiguate
two contexts after extensive training. These data suggest that the
continuous production of new dentate neurons plays a crucial role
in extracting and separating efficiently contextual representation
in order to discriminate features within events. © 2010 Wiley-Liss,
Inc.},
issn = {1098-1063},
keywords = {adult neurogenesis, hippocampus, mice, contextual discrimination},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hipo.20895}
}
@ARTICLE{Troost2008,
author = {Troost, Freddy and van Baarlen, Peter and Lindsey, Patrick and Kodde,
Andrea and de Vos, Willem and Kleerebezem, Michiel and Brummer, Robert-Jan},
title = {Identification of the transcriptional response of human intestinal
mucosa to Lactobacillus plantarum WCFS1 in vivo},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {374},
number = {1},
abstract = {BACKGROUND:There is limited knowledge on the extent and dynamics of
the mucosal response to commensal and probiotic species in the human
intestinal lumen. This study aimed to identify the acute, time-dependent
responses of intestinal mucosa to commensal Lactobacillus plantarum
WCFS1 in vivo in two placebo-controlled human intervention studies
in healthy volunteers. Transcriptional changes in duodenal mucosa
upon continuous intraduodenal infusion of L. plantarum WCFS1 for
one- and six h, respectively, were studied using oro- and nasogastric
intubations with dedicated orogastric catheters and tissue sampling
by standard flexible gastroduodenoscopy.RESULTS:One- and six-h exposure
of small intestinal mucosa to L. plantarum WCFS1 induced differential
expression of 669 and 424 gene reporters, respectively. While short-term
exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and
cell cycle progression, cells switched to a more proliferative phase
after prolonged exposure with an overall expression profile characterized
by upregulation of genes involved in lipid metabolism, cellular growth
and development. Cell death and immune responses were triggered,
but cell death-executing genes or inflammatory signals were not expressed.
Proteome analysis showed differential expression of several proteins.
Only the microsomal protein 'microsomal triglyceride transfer protein'
was regulated on both the transcriptional and the protein level in
all subjects.CONCLUSION:Overall, this study showed that intestinal
exposure to L. plantarum WCFS1 induced consistent, time-dependent
transcriptional responses in healthy intestinal mucosa. This extensive
exploration of the human response to L. plantarum WCFS1 could eventually
provide molecular support for specific or probiotic activity of this
strain or species, and exemplifies the strength of the applied technology
to identify the potential bio-activity of microbes in the human intestine.},
doi = {10.1186/1471-2164-9-374},
issn = {1471-2164},
pubmedid = {18681965},
url = {http://www.biomedcentral.com/1471-2164/9/374}
}
@ARTICLE{Trost2008,
author = {Trost, Zoran and Marc, Janja and Sok, Miha and Cerne, Darko},
title = {Increased Apolipoprotein E Gene Expression and Protein Concentration
in Lung Cancer Tissue Do Not Contribute to the Clinical Assessment
of Non-small Cell Lung Cancer Patients},
journal = {Archives of Medical Research},
year = {2008},
volume = {39},
pages = {663--667},
number = {7},
month = oct,
abstract = {Background We tested the hypothesis that apolipoprotein E (apo E)
gene expression and protein concentration are increased in resectable
non-small cell lung cancer tissue and that these apo E tissue estimations
may be benefitially used in clinical assessment of non-small cell
lung cancer patients.Methods Paired samples of lung cancer and adjacent,
appartently healthy, non-cancer lung tissue were collected from 42
patients with resectable non-small cell lung cancer. Apo E gene expression
in tissue was measured by quantitative PCR. Apo E protein in tissue
and serum was quantified by a nephelometric method. Patients were
followed for 3 years.Results Apo E gene expression and protein concentration
were 1.6 and 4.1-fold higher in the cancer tissue than in the adjacent
non-cancer tissue (p <0.0001 in both cases). Increase of apo E protein
concentration in the cancer tissue (relative to the non-cancer tissue)
correlated with the decrease of apo E protein concentration in the
serum (p = 0.021). However, none of these apo E estimations related
to stage of cancer or histological type of tumor and do not predict
patient survival.Conclusions Our preliminary study shows that despite
the distinct increase of apo E gene expression and protein concentration
in the cancer tissue and the concurrent decrease of apo E protein
concentration in the serum, the measured apo E values have limited
usefulness in clinical assessment of patients with resectable non-small
cell lung cancer.},
issn = {0188-4409},
keywords = {Apolipoprotein E, Gene expression, Protein concentration, Non-small
cell lung cancer tissue, Clinical assessment of patient},
url = {http://www.sciencedirect.com/science/article/B6VNM-4T9M280-8/2/2a65f5ba2b96ec12bae2e62c4c00e082}
}
@ARTICLE{Trost2010,
author = {Trost, Zoran and Trebse, Rihard and Prezelj, Janez and Komadina,
Radko and Logar, Darja Bitenc and Marc, Janja},
title = {A microarray based identification of osteoporosis-related genes in
primary culture of human osteoblasts},
journal = {Bone},
year = {2010},
volume = {46},
pages = {72--80},
number = {1},
month = jan,
abstract = {Genetic factors influencing the pathogenesis of osteoporosis are still
largely unknown. We employed genome-wide gene expression approach
in order to discover novel genes involved in the pathogenesis of
osteoporosis. To this end, primary cultures of osteoblasts isolated
from osteoporotic and non-osteoporotic human bone tissue samples
were prepared. One thousand six hundred six genes were found to be
differentially expressed, indicating increased demand for protein
synthesis and decreased cell proliferation rate in osteoblasts from
osteoporotic tissue as compared to osteoblasts from non-osteoporotic
tissue. At first, top four genes, based on the microarray data and
potential role in bone metabolism, were further studied in bone tissue
samples of 55 patients. PTN and COL15A1 were both downregulated in
osteoporotic bone tissue (6.2- and 3.4-fold, respectively, both p < 0.05),
while IBSP and CXCL2 were both upregulated (5.7-fold, p < 0.05, and
2.1-fold, p > 0.05). Further biostatistical analysis of the microarray
data by gene set enrichment analysis suggested oxidative stress may
have an important part in the pathogenesis of osteoporosis. Thus,
secondly, we tested it by an in vitro assay on human osteosarcoma
cell line cells treated with hydrogen peroxide. After 72 h of treatment
with 500 [mu]M hydrogen peroxide, the upregulation of the same genes
involved in the response to oxidative stress as on the microarrays
was observed: MT1G (metallothionein 1G, 22.1-fold, p < 0.05), TXNRD1
(thioredoxin reductase 1, 3.7-fold, p < 0.05), AOX1 (aldehyde oxidase
1, 24.5-fold, p < 0.05) and GSR (glutathione reductase, 4.7-fold,
p < 0.05). Our results present a novel list of genes and metabolic
pathways that may be associated with the pathogenesis of osteoporosis.
PTN, CXCL2, COL15A1, IBSP, AOX1, MT1G, GSR and TXNRD1 are candidate
genes for further studies in the assessment of the genetic susceptibility
to osteoporosis. In addition, differences in protein synthesis, cell
proliferation rate and response to oxidative stress may also be involved
in the pathogenesis of osteoporosis.},
issn = {8756-3282},
keywords = {Bone tissue, Oxidative stress, Gene expression, PTN, CXCL2},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4X97D0V-1/2/067ad6d0977a4b7b4e2d4ef79ea4b02a}
}
@ARTICLE{Trotter2005,
author = {Trotter, James Raffaello and Ernst, Nancy Lewis and Carnes, Jason
and Panicucci, Brian and Stuart, Kenneth},
title = {A Deletion Site Editing Endonuclease in Trypanosoma brucei},
journal = {Molecular Cell},
year = {2005},
volume = {20},
pages = {403--412},
number = {3},
month = nov,
abstract = {Summary RNA editing in Trypanosoma brucei inserts and deletes uridines
in mitochondrial mRNAs by a series of enzymatic steps that are catalyzed
by a multiprotein complex, the editosome. KREPB1 and two related
editosome proteins KREPB2 and KREPB3 contain motifs that suggest
endonuclease and RNA/protein interaction functions. Repression of
KREPB1 expression in procyclic forms by RNAi inhibited growth, in
vivo editing, and in vitro endoribonucleolytic cleavage of deletion
substrates. However, cleavage of insertion substrates and the exoUase,
TUTase, and ligase catalytic activities of editing were retained
by 20S editosomes. Repression of expression of an ectopic KREPB1
allele in bloodstream forms lacking both endogenous alleles or exclusive
expression of KREPB1 with point mutations in the putative RNase III
catalytic domain also blocked growth, in vivo editing, and abolished
cleavage of deletion substrates, without affecting the other editing
steps. These data indicate that KREPB1 is an endoribonuclease that
is specific for RNA editing deletion sites.},
issn = {1097-2765},
url = {http://www.sciencedirect.com/science/article/B6WSR-4HHX2B2-7/2/0b8baba4bc44aa6efd58df326a008f4a}
}
@ARTICLE{Trougakos2010,
author = {Trougakos, Ioannis P. and Chondrogianni, Niki and Amarantos, Ioannis
and Blake, Jonathon and Schwager, Christian and Wirkner, Ute and
Ansorge, Wilhelm and Gonos, Efstathios S.},
title = {Genome-wide transcriptome profile of the human osteosarcoma Sa OS
and U-2 OS cell lines},
journal = {Cancer Genet Cytogenet},
year = {2010},
volume = {196},
pages = {109--118},
number = {2},
month = jan,
abstract = {With the use of genome-wide cDNA microarrays, we investigated the
transcriptome profile of the human osteosarcoma Sa OS and U-2 OS
cell lines. In all, 1,098 chip entries were differentially regulated
in the two cell lines; of these, 796 entries corresponded to characterized
mRNAs. The identified genes are mostly expressed in epithelial tissues
and localize on chromosomes 1, 10, and 20. Furthermore, signaling
cascades for cell cycle, glycolysis, and gluconeogenesis, the p53
pathway, cell communication, and focal adhesion were found to be
differently regulated in the two cell lines. The transcriptome profiles
reported here provide novel information about the considerable molecular
differences between these two widely used human osteosarcoma cell
lines.},
issn = {0165-4608},
publisher = {Elsevier/North-Holland.},
refid = {S0165-4608(09)00576-7},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0165460809005767?showall=true}
}
@ARTICLE{Trouve2007,
author = {Trouvé, Pascal and Le Drévo, Marie-Anne and Kerbiriou, Mathieu and
Friocourt, Gaëlle and Fichou, Yann and Gillet, Danièle and Férec,
Claude},
title = {Annexin V is directly involved in cystic fibrosis transmembrane conductance
regulator's chloride channel function},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
year = {2007},
volume = {1772},
pages = {1121--1133},
number = {10},
month = oct,
abstract = {The cystic fibrosis transmembrane conductance regulator (CFTR) functions
as a cAMP-activated chloride channel, which is regulated by protein-protein
interactions. The extent to which CFTR is regulated by these interactions
remains unknown. Annexin V is overexpressed in cystic fibrosis (CF),
and given the functional properties of annexin V and CFTR we considered
whether they are associated and if so whether this has implications
for CFTR function. Using co-immunoprecipitation and overlay experiments,
we show that annexin V is associated with nucleotide-binding domain
1 (NBD1) of CFTR. Surface plasmon resonance (SPR) indicated different
KD values in the absence and presence of both calcium and ATP, suggesting
that this interaction is calcium- and ATP-dependent. Using an siRNA
approach and overexpression, we showed that CFTR chloride channel
function and its localization in the cell membranes were dependent
on annexin V expression. We concluded that annexin V is necessary
for normal CFTR chloride channel activity. Furthermore, we show that
CFTR and annexin V are partially co-distributed in normal epithelial
cells in human bronchi. In conclusion, we show for the first time
that annexin V is associated with CFTR and is involved in its function.},
issn = {0925-4439},
keywords = {Protein-protein interaction, Normal CFTR function, Protein localization},
url = {http://www.sciencedirect.com/science/article/B6T1Y-4PD4XCK-1/2/3b3a823e5213f2873e9c60f856bd0b1a}
}
@ARTICLE{Trubiroha2010,
author = {Trubiroha, Achim and Kroupova, Hana and Wuertz, Sven and Frank, Sabrina
N. and Sures, Bernd and Kloas, Werner},
title = {Naturally-induced endocrine disruption by the parasite Ligula intestinalis
(Cestoda) in roach (Rutilus rutilus)},
journal = {General and Comparative Endocrinology},
year = {2010},
volume = {166},
pages = {234--240},
number = {2},
month = apr,
issn = {0016-6480},
keywords = {Endocrine disruption, Tapeworm, Reproduction, Biomarker, Fish, Roach,
Rutilus rutilus, Vitellogenin, Aromatase, Oestrogens, Androgens},
url = {http://www.sciencedirect.com/science/article/B6WG0-4X49YC1-1/2/10e881cb5464bd009b9495d8d01bb771}
}
@ARTICLE{Trubiroha2009,
author = {Trubiroha, Achim and Wuertz, Sven and Frank, Sabrina N. and Sures,
Bernd and Kloas, Werner},
title = {Expression of gonadotropin subunits in roach (Rutilus rutilus, Cyprinidae)
infected with plerocercoids of the tapeworm Ligula intestinalis (Cestoda)},
journal = {International Journal for Parasitology},
year = {2009},
volume = {39},
pages = {1465--1473},
number = {13},
month = nov,
abstract = {Plerocercoids of the tapeworm Ligula intestinalis (Cestoda: Bothriocephalidea)
have been reported to inhibit gametogenesis of their intermediate
fish hosts. However, mechanistic studies are rare and the proximate
cues leading to impaired reproduction still remain unknown. In the
present study we investigated the effects of infection by L. intestinalis
on reproductive parameters of roach (Rutilus rutilus, Cyprinidae),
a common fish host of this parasite. Field studies on roach demonstrated
that in both genders infection prevented gonad development. As revealed
by quantitative PCR, infection was accompanied by essentially lower
pituitary expression of follicle-stimulating hormone [beta]-subunit
(FSH[beta]) and luteinizing hormone [beta]-subunit (LH[beta]) mRNA
compared with uninfected roach, providing clear evidence for gonadotropin-insufficiency
as the cause of arrested gametogenesis. Under controlled laboratory
conditions infected roach showed lower mRNA levels of FSH[beta] but
not of LH[beta], despite histology revealing similar gonad stages
as in uninfected conspecifics. These findings indicate the involvement
of FSH rather than LH in mediating effects of infection early during
gonad development in roach. Moreover, the impact of L. intestinalis
on reproductive parameters of roach appeared to be independent of
the parasite burden. Together, these data provide valuable information
on the role of FSH and LH as mediators of parasite-induced sterilization
in a vertebrate and implicate the selective inhibition of host reproduction
by L. intestinalis as a natural source of endocrine disruption in
fish.},
issn = {0020-7519},
keywords = {Host-parasite interaction, Roach, Rutilus rutilus, Ligula intestinalis,
Plerocercoid, Reproduction, Gonadotropin, Host sterilization},
url = {http://www.sciencedirect.com/science/article/B6T7F-4WCBVGS-2/2/953f8895a5fd879c1b4e16c326565a87}
}
@ARTICLE{Trujillo2011,
author = {Trujillo, Kristina A. and Heaphy, Christopher M. and Mai, Minh and
Vargas, Keith M. and Jones, Anna C. and Vo, Phung and Butler, Kimberly
S. and Joste, Nancy E. and Bisoffi, Marco and Griffith, Jeffrey K},
title = {Markers of fibrosis and epithelial to mesenchymal transition demonstrate
field cancerization in histologically normal tissue adjacent to breast
tumors},
journal = {International Journal of Cancer},
year = {2011},
volume = {129},
pages = {1310--1321},
number = {6},
abstract = {Previous studies have shown that a field of genetically altered but
histologically normal tissue extends 1 cm or more from the margins
of human breast tumors. The extent, composition and biological significance
of this field are only partially understood, but the molecular alterations
in affected cells could provide mechanisms for limitless replicative
capacity, genomic instability and a microenvironment that supports
tumor initiation and progression. We demonstrate by microarray, qRT-PCR
and immunohistochemistry a signature of differential gene expression
that discriminates between patient-matched, tumor-adjacent histologically
normal breast tissues located 1 cm and 5 cm from the margins of breast
adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature
includes genes involved in extracellular matrix remodeling, wound
healing, fibrosis and epithelial to mesenchymal transition (EMT).
Myofibroblasts, which are mediators of wound healing and fibrosis,
and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which
are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse
in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty.
Accordingly, EMT markers S100A4 and vimentin were elevated in both
luminal and myoepithelial cells, and EMT markers α-smooth muscle
actin and SNAIL were elevated in luminal epithelial cells of TAHN-1
tissues. These results identify cellular processes that are differentially
activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts
as likely mediators of these processes, provide evidence that EMT
is occurring in histologically normal tissues within the affected
field and identify candidate biomarkers to investigate whether or
how field cancerization contributes to the development of primary
or recurrent breast tumors.},
doi = {10.1002/ijc.25788},
issn = {1097-0215},
keywords = {field cancerization, wound healing, fibrosis, breast cancer, epithelial
to mesenchymal transition},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25788}
}
@ARTICLE{Truman2006,
author = {Truman, William and de Zabala, Marta Torres and Grant, Murray},
title = {Type III effectors orchestrate a complex interplay between transcriptional
networks to modify basal defence responses during pathogenesis and
resistance},
journal = {The Plant Journal},
year = {2006},
volume = {46},
pages = {14--33},
number = {1},
abstract = {Summary To successfully infect a plant, bacterial pathogens inject
a collection of Type III effector proteins (TTEs) directly into the
plant cell that function to overcome basal defences and redirect
host metabolism for nutrition and growth. We examined (i) the transcriptional
dynamics of basal defence responses between Arabidopsis thaliana
and Pseudomonas syringae and (ii) how basal defence is subsequently
modulated by virulence factors during compatible interactions. A
set of 96 genes displaying an early, sustained induction during basal
defence was identified. These were also universally co-regulated
following other bacterial basal resistance and non-host responses
or following elicitor challenges. Eight hundred and eighty genes
were conservatively identified as being modulated by TTEs within
12Â h post-inoculation (hpi), 20% of which represented transcripts
previously induced by the bacteria at 2Â hpi. Significant over-representation
of co-regulated transcripts encoding leucine rich repeat receptor
proteins and protein phosphatases were, respectively, suppressed
and induced 12Â hpi. These data support a model in which the pathogen
avoids detection through diminution of extracellular receptors and
attenuation of kinase signalling pathways. Transcripts associated
with several metabolic pathways, particularly plastid based primary
carbon metabolism, pigment biosynthesis and aromatic amino acid metabolism,
were significantly modified by the bacterial challenge at 12Â hpi.
Superimposed upon this basal response, virulence factors (most likely
TTEs) targeted genes involved in phenylpropanoid biosynthesis, consistent
with the abrogation of lignin deposition and other wall modifications
likely to restrict the passage of nutrients and water to the invading
bacteria. In contrast, some pathways associated with stress tolerance
are transcriptionally induced at 12Â hpi by TTEs.},
issn = {1365-313X},
keywords = {Pseudomonas syringae, type III effector, basal defence, pathogenicity,
transcriptional reprogramming, Arabidopsis thaliana},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2006.02672.x}
}
@ARTICLE{Trummer2008,
author = {Trummer, Evelyn and Ernst, Wolfgang and Hesse, Friedemann and Schriebl,
Kornelia and Lattenmayer, Christine and Kunert, Renate and Vorauer-Uhl,
Karola and Katinger, Hermann and Müller, Dethardt},
title = {Transcriptional profiling of phenotypically different Epo-Fc expressing
CHO clones by cross-species microarray analysis},
journal = {Biotechnology Journal},
year = {2008},
volume = {3},
pages = {924--937},
number = {7},
abstract = {Abstract 10.1002/biot.200800038.abs Chinese hamster ovary (CHO) cells
exhibit large variabilities regarding growth, recombinant protein
production and post-translational processing during cell line development
and clone selection. To accelerate the development of stable high
quality cell factories, new efficient strategies for cell screening
and clone selection are required. In our work, we combined phenotypic
characterisation of recombinant CHO clones during early cell line
development with transcription profile analysis using cross-species
microarrays. The objective was to identify genes or gene patterns
that correlate with clone specific alterations in terms of productivity,
sialylation capacity and stress resistance. In all high producer
clones transcriptional profiling revealed a common enrichment of
gene ontology categories related to protein metabolism, transcription,
nucleus and nucleolus, whereas no common genes were differentially
regulated in clones showing higher sialylation capacities. Furthermore,
we identified predictive stress-related marker genes that were up-regulated
in one clone without showing the corresponding phenotype at an early
stage of development. Thus, we successfully applied gene expression
profiling to allocate transcriptomal differences to specific phenotypes
that changed during cell line development. These promising results
will further increase our efforts to develop CHO specific microarrays
that deliver information about the suitability of a clone candidate
for industrial production.},
issn = {1860-7314},
keywords = {Chinese hamster ovary cells, Cross-species, Oligonucleotide microarray,
Recombinant protein production, Transcription analysis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/biot.200800038}
}
@ARTICLE{Truong2011,
author = {Truong, Thuy T. and Huynh, Kyle and Nakatsu, Martin N. and Deng,
Sophie X.},
title = {SSEA4 Is a Potential Negative Marker for the Enrichment of Human
Corneal Epithelial Stem/Progenitor Cells},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {6315-6320},
number = {9},
abstract = {Purpose.To examine the expression of stage-specific embryonic antigen-4
(SSEA4) in the epithelium of the human ocular surface and characterize
SSEA4+ and SSEA4- limbal epithelial cells. Methods.SSEA4 expression
in the human cornea and limbus was examined by RT-PCR and immunohistochemistry.
SSEA4+ and SSEA4- cells were then separated by using magnetic beads.
The phenotypes of these two cell populations were evaluated on the
basis of cell size, clonogenic assay, and expression of putative
limbal stem cell (LSC) and corneal epithelial differentiation markers.
Results.SSEA4 was expressed in all layers of the corneal and anterior
limbal epithelia. Discrete clusters of SSEA4+ cells were present
in the central and posterior limbal epithelia. SSEA4+ cells accounted
for an average of 40% of the total limbal epithelial cells. The SSEA4-
population contained five times more small cells ([≤]11 {micro}m
in diameter) than did the SSEA4+ population. The expression levels
of the putative LSC markers ABCG2, {Delta}Np63, and cytokeratin (K)14
were significantly higher in the SSEA4- population than in the SSEA4+
population. The SSEA4- cells also expressed a significantly higher
level of N-cadherin, but a lower level of the differentiation marker
K12. The colony-forming efficiency in the SSEA4- population was 25.2%
(P = 0.04) and 1.6-fold (P < 0.05) higher than in the unsorted population
and the SSEA4+ population, respectively. Conclusions.SSEA4 is highly
expressed in differentiated corneal epithelial cells, and SSEA4-
limbal epithelial cells contain a higher proportion of limbal stem/progenitor
cells. SSEA4 could be used as a negative marker to enrich the isolation
of LSCs.},
doi = {10.1167/iovs.11-7518},
eprint = {http://www.iovs.org/cgi/reprint/52/9/6315.pdf},
url = {http://www.iovs.org/cgi/content/abstract/52/9/6315}
}
@ARTICLE{Trzeciakiewicz2010,
author = {Trzeciakiewicz, Anna and Habauzit, Veronique and Mercier, Sylvie
and Barron, Denis and Urpi-Sarda, Mireia and Manach, Claudine and
Offord, Elizabeth and Horcajada, Marie-Noelle},
title = {Molecular Mechanism of Hesperetin-7-O-glucuronide, the Main Circulating
Metabolite of Hesperidin, Involved in Osteoblast Differentiation},
journal = {Journal of Agricultural and Food Chemistry},
year = {2010},
volume = {58},
pages = {668-675},
number = {1},
note = {PMID: 19921838},
doi = {10.1021/jf902680n},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf902680n},
url = {http://pubs.acs.org/doi/abs/10.1021/jf902680n}
}
@ARTICLE{Trzeciakiewicz2010a,
author = {Trzeciakiewicz, Anna and Habauzit, Veronique and Mercier, Sylvie
and Lebecque, Patrice and Davicco, Marie-Jeanne and Coxam, Veronique
and Demigne, Christian and Horcajada, Marie-Noëlle},
title = {Hesperetin stimulates differentiation of primary rat osteoblasts
involving the BMP signalling pathway},
journal = {J Nutr Biochem},
year = {2010},
volume = {21},
pages = {424--431},
number = {5},
month = may,
abstract = {Hesperidin found in citrus fruits has been reported to be a promising
bioactive compound for maintaining an optimal bone status in ovariectomized
rodent models. In this study, we examined the capacity of hesperetin
(Hp) to affect the proliferation, differentiation and mineralization
of rodent primary osteoblasts. Then, the impact of Hp on signalling
pathways known to be implicated in bone formation was explored. We
exposed osteoblasts to physiological concentrations of 1 μM Hp (Hp1)
and 10 μM Hp (Hp10). Neither proliferation nor mineralization was
affected by Hp at either dose during 19 days of exposure. Hp at both
doses enhanced differentiation by significantly increasing alkaline
phosphatase (ALP) activity from Day 14 of exposure (Day 19: Hp1:
+9%, Hp10: +14.8% vs. control; P<.05). However, Hp did not induce
an obvious formation of calcium nodules. The effect of Hp10 on ALP
was inhibited by addition of noggin protein, suggesting a possible
action of this flavanone through the bone morphogenetic protein (BMP)
pathway. Indeed, Hp10 significantly induced (1.2- to 1.4-fold) mRNA
expression of genes involved in this signalling pathway (i.e., BMP2,
BMP4, Runx2 and Osterix) after 48 h of exposure. This was strengthened
by enhanced phosphorylation of the complex Smad1/5/8. Osteocalcin
mRNA level was up-regulated by Hp only at 10 μM (2.2 fold vs. control).
The same dose of Hp significantly decreased osteopontin (OPN) protein
level (50% vs. control) after 14 days of culture. Our findings suggest
that Hp may regulate osteoblast differentiation through BMP signalling
and may influence the mineralization process by modulating OPN expression.},
issn = {0955-2863},
keywords = {Hesperetin, Flavonoid, Osteoblast, Differentiation, Bone morphogenetic
proteins (BMP)},
publisher = {Elsevier Science,},
refid = {S0955-2863(09)00033-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0955286309000333?showall=true}
}
@ARTICLE{Treton2011,
author = {Tréton, Xavier and Pédruzzi, Eric and Cazals-Hatem, Dominique and
Grodet, Alain and Panis, Yves and Groyer, André and Moreau, Richard
and Bouhnik, Yoram and Daniel, Fanny and Ogier-Denis, Eric},
title = {Altered Endoplasmic Reticulum Stress Affects Translation in Inactive
Colon Tissue From Patients With Ulcerative Colitis},
journal = {Gastroenterology},
year = {2011},
volume = {141},
pages = {1024--1035},
number = {3},
month = sep,
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disorder that affects
the colonic epithelium. Epidemiology studies indicate an environmental
component is involved in pathogenesis, although the primary changes
in the digestive epithelium that cause an uncontrolled inflammatory
response are not known. Animal studies have shown that altered endoplasmic
reticulum (ER) stress response initiates intestinal inflammation
in epithelial tissues, but abnormalities associated with ER stress
have not been identified in patients with UC. Using immunoblotting,
real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence
analyses, we assessed ER stress signaling in uninflammed colonic
mucosa from patients with UC and controls. Genome-wide microarray
analysis of actively translated polysome-bound messenger RNA was
performed using samples of unaffected mucosa from patients with UC,
and data were compared with those from controls. Inositol-requiring
kinase and activating transcription factor signaling pathways were
activated in inactive colonic epithelium from patients with UC; these
mediate proinflammatory and regenerative responses. Blocking phosphorylation
of the translation initiation factor 2 (eIF2α), which mediates the
integrated stress response, deregulated initiation of translation
and reduced the numbers of stress granules in colonic epithelial
cells from patients with UC. Genome-wide microarray analysis of actively
translated, polysome-bound messenger RNA from patients revealed changes
in protein translation that altered colonic epithelial barrier function
(levels of detoxification and antioxidant enzymes and proteins that
regulate the cell cycle, cell-cell adhesion, and secretion), compared
with controls. Colonic mucosa samples from patients with UC have
defects in the eIF2α pathway that controls protein translation and
the cell stress response. This pathway might be investigated to identify
new therapeutic targets for patients with UC.},
issn = {0016-5085},
keywords = {Integrated Stress Response, Inflammatory Bowel Disease, Unfolded Protein
Response, Proteostasis, ATF4, activating transcription factor 4,
ATF6, activating factor 6, CHOP, CCAAT/-enhancer-binding protein
homologous protein, eIF2, eukaryotic initiation factor 2, ER, endoplasmic
reticulum, IBD, inflammatory bowel disease, Ig, immunoglobulin, IRE1,
inositol-requiring kinase 1, ISR, integrated stress response, JNK,
c-Jun-N-terminal kinases, miRNAs, microRNAs, mRNA, messenger RNA,
PERK, protein kinase RNA-like endoplasmic reticulum kinase, SG, stress
granule, UC, ulcerative colitis, UPR, unfolded protein response,
XBP-1, X-box binding protein},
publisher = {W.B. Saunders},
refid = {S0016-5085(11)00698-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0016508511006986?showall=true}
}
@ARTICLE{Tsai2010a,
author = {Tsai, Hsiang-Jung and Chiu, Chih-Hsien and Wang, Chia-Lan and Chou,
Chung-Hsi},
title = {A time-course study of gene responses of chicken granulosa cells
to Salmonella Enteritidis infection},
journal = {Veterinary Microbiology},
year = {2010},
volume = {144},
pages = {325--333},
number = {3-4},
month = aug,
abstract = {Consumption of eggs contaminated with Salmonella Enteritidis (SE)
has been recognized as one of the important causes of human foodborne
salmonellosis. Chicken granulosa cells (cGCs) comprise the last tissue
layer surrounding the yolk in preovulatory follicles and are a preferred
site for SE invasion. To understand the cGC response to SE infection,
we conducted an in vitro time-course study to identify cGC transcriptional
changes using chicken whole genome microarrays. The expression of
135 (4 h postinfection) and 120 cGC genes (48 h postinfection) were
altered (P < .01) compared to uninfected cells. Many of the altered
genes were related to immune response, physiological processes, signal
transduction, and transcription. Furthermore, we also found that
the Jak-STAT pathway, which is essential in the regulation of cellular
cytokines and growth factors, was highly active in this study. Among
the genes identified by microarray, the mRNA levels of TLR15, IL-6,
CXCLi1, CXCLi2, and K203 were shown to be upregulated by real-time
RT-PCR (qRT-PCR). In contrast, the mRNA levels of RASD1 and HB-EGF
decreased according to both microarray and qRT-PCR analyses. These
results suggest that during the SE infection, cGCs recruit cells
of the innate immune responses; the infection may also induce suppression
of cGC cell proliferation, which alters follicular development and
ovulation.},
issn = {0378-1135},
keywords = {Salmonella Enteritidis, Chicken granulosa cell, Microarray, qRT-PCR,
Gene expression},
url = {http://www.sciencedirect.com/science/article/B6TD6-4Y7P4M0-1/2/379bb592e37c68980021c22b2604ae9d}
}
@ARTICLE{Tsai2009,
author = {Tsai, K.-J. and Yang, C.-H. and Lee, P.-C. and Wang, W.-T. and Chiu,
M.-J. and Shen, C.-K.J.},
title = {Asymmetric expression patterns of brain transthyretin in normal mice
and a transgenic mouse model of Alzheimer's disease},
journal = {Neuroscience},
year = {2009},
volume = {159},
pages = {638--646},
number = {2},
month = mar,
abstract = {Brain asymmetry is linked with several neurological diseases, and
transthyretin (TTR) is a protein sequestering [beta]-amyloid (A[beta])
and helping to prevent the Alzheimer's disease (AD). We show, by
real time reverse transcription-polymerase chain reaction (RT-PCR),
in situ hybridization and Western blotting, that TTR exhibits a pattern
of adult male-specific, leftward distribution in the mouse brain.
This asymmetry appeared to be mainly due to the asymmetric distribution
of the choroid plexus cells in the ventricles. Unlike the normal
mice, however, the hemispheric levels of TTR transcripts of 2- and
6-month-old Tg2576 mice, a transgenic AD mouse model overexpressing
A[beta], were symmetric in both sexes. Furthermore, at the age of
10 months when the pathological AD-like features had developed, the
level of TTR transcripts in the left hemisphere of the male Tg2576
became significantly lower than the right one. This lowering of TTR
transcript is accompanied with a higher A[beta] level in the left
hemisphere of the 10-month Tg2576 males. Finally, for both genders,
the TTR transcript levels in the two hemispheres of aged Tg2576 mice
were lower than either the adult Tg2576 or the aged nontransgenic
controls. Based on the above, we suggest scenarios to correlate the
changes in the levels and hemispheric patterns of TTR expression
to the pathogenesis of AD.},
issn = {0306-4522},
keywords = {Alzheimer's disease, asymmetry, gene expression, mouse brain, transthyretin},
url = {http://www.sciencedirect.com/science/article/B6T0F-4V94X23-2/2/2266725da84f67cf6f3657bf2d76453d}
}
@ARTICLE{Tsai2007,
author = {Tsai, Ming-Song and Hwang, Shiaw-Min and Chen, Kuang-Den and Lee,
Yun-Shien and Hsu, Li-Wen and Chang, Yu-Jen and Wang, Chao-Nin and
Peng, Hsiu-Huei and Chang, Yao-Lung and Chao, An-Shine and Chang,
Shuenn-Dyh and Lee, Kuan-Der and Wang, Tzu-Hao and Wang, Hsin-Shih
and Soong, Yung-Kuei},
title = {Functional Network Analysis of the Transcriptomes of Mesenchymal
Stem Cells Derived from Amniotic Fluid, Amniotic Membrane, Cord Blood,
and Bone Marrow},
journal = {STEM CELLS},
year = {2007},
volume = {25},
pages = {2511--2523},
number = {10},
abstract = {Abstract 10.1634/stemcells.2007-0023.abs Using high-density oligonucleotide
microarrays and functional network analyses, we examined whether
MSCs derived from four different origins exhibited unique gene expression
profiles individually and then compared the gene expression profiles
of all MSCs with those of fetal organs. Our results indicated that
within each group of MSCs from the same origin, the variability of
the gene expression levels was smaller than that between groups of
different origins. Functional genomic studies revealed the specific
roles of MSCs from different origins. Our results suggest that amniotic
fluid MSCs may initiate interactions with the uterus by upregulating
oxytocin and thrombin receptors. Amniotic membrane MSCs may play
a role in maintaining homeostasis of fluid and electrolytes by regulating
the networks of endothelin, neprilysin, bradykinin receptors, and
atrial natriuretic peptide. Cord blood MSCs may be involved in innate
immune systems as the neonatal defense system against the earliest
encountered pathogens. Adult bone marrow MSCs may be an important
source not only of all blood lineages but also of bone formation.
However, in spite of the different gene expression profiles seen
in MSCs derived from different origins, a set of core gene expression
profiles was preserved in these four kinds of MSCs. The core signature
transcriptomes of all MSCs, when contrasted against those of fetal
organs, included genes involved in the regulation of extracellular
matrix and adhesion, transforming growth factor-β receptor signaling,
and the Wnt signaling pathways. Disclosure of potential conflicts
of interest is found at the end of this article.},
issn = {1549-4918},
keywords = {Mesenchymal stem cells, Microarray, Transcriptome, Functional network
analysis},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-0023}
}
@ARTICLE{Tsai2011,
author = {Tsai, S. and Hardison, N.E. and James, A.H. and Motsinger-Reif, A.A.
and Bischoff, S.R. and Thames, B.H. and Piedrahita, J.A.},
title = {Transcriptional profiling of human placentas from pregnancies complicated
by preeclampsia reveals disregulation of sialic acid acetylesterase
and immune signalling pathways},
journal = {Placenta},
year = {2011},
volume = {32},
pages = {175--182},
number = {2},
month = feb,
abstract = {The placenta plays an important role as a regulator of fetal nutrition
and growth throughout development and placental factors contribute
to gestational abnormalities such as preeclampsia. This study describes
the genome-wide gene expression profiles of a large (n = 60) set
of human placentas in order to uncover gene expression patterns associated
with preeclampsia. In addition to confirming changes in expression
of soluble factors associated with preeclampsia such as sFLT1 (soluble
fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin
alpha), we also find changes in immune-associated signaling pathways,
offering a potential upstream explanation for the shallow trophoblast
invasion and inadequate uterine remodeling typically observed in
pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated
placental upregulation of sialic acid acetylesterase (SIAE), a gene
functionally associated with autoimmune diseases.},
issn = {0143-4004},
keywords = {Placenta, Preeclampsia, Maternal hypertension, Sialic acid acetylesterase},
url = {http://www.sciencedirect.com/science/article/pii/S0143400410004455}
}
@ARTICLE{Tsai2010,
author = {Tsai, Yueh-Ting and Cheng, Po-Ching and Liao, Jiunn-Wang and Pan,
Tzu-Ming},
title = {Effect of the administration of Lactobacillus paracasei subsp. paracasei
NTU 101 on Peyer's patch-mediated mucosal immunity},
journal = {International Immunopharmacology},
year = {2010},
volume = {10},
pages = {791--798},
number = {7},
month = jul,
abstract = {The role of lactic acid bacteria in gut mucosal immunity was investigated
by comparing the enhanced effects in the Peyer's patches and spleen
of BALB/c mice fed daily with Lactobacillus paracasei subsp. paracasei
NTU 101 for 3 to 9 weeks. After feeding with Lactobacillus, the percentage
of CD4+ T cells in both Peyer's patches and the spleen was significantly
increased; however, expression of CD 154 molecules, which play a
pivotal role in cell-to-cell communication, on CD4+ T cells and the
percentage of B220+ B cells increased only in Peyer's patches. Compared
with systemic serum IgA, Peyer's patch-derived immunomodulation induced
higher levels of intestinal IgA+-producing cells in the lamina propria.
Our data also showed that feeding with Lactobacillus induced stronger
CD4+ T cell-dendritic cell interaction, enhanced CD4+ T cell and
B cell proliferation, and increased IL-1[beta], IL-10, IL-12, IFN-[gamma],
and TNF-[alpha] mRNA expression in Peyer's patches, but not in the
spleen. Here, we demonstrate that following Lactobacillus treatment,
Peyer's patches exhibited a more distinct capacity to induce CD4+
T cell-dendritic cell interactions, lymphocyte proliferation, and
cytokine secretion than the spleen, and thereby promoted greater
intestinal IgA production that could enhance immunosurveillance to
prevent intestinal infections or other intestinal pathologies.},
issn = {1567-5769},
keywords = {Peyer's patches, Mucosal immunity, Immunomodulation, Probiotics},
url = {http://www.sciencedirect.com/science/article/B6W7N-4YXK4HP-1/2/af5424f279bfea4eb73acb9a219a0d2a}
}
@ARTICLE{Tsai2011a,
author = {Tsai, Yen-Yin and Huang, Yi-Huei and Chao, Ya-Li and Hu, Kuang-Yu
and Chin, Li-Te and Chou, Shiu-Huey and Hour, Ai-Ling and Yao, Yeong-Der
and Tu, Chi-Shun and Liang, Yao-Jen and Tsai, Cheng-Yuh and Wu, Hao-Yu
and Tan, Shan-Wen and Chen, Han-Min},
title = {Identification of the Nanogold Particle-Induced Endoplasmic Reticulum
Stress by Omic Techniques and Systems Biology Analysis},
journal = {ACS Nano},
year = {2011},
volume = {5},
pages = {9354-9369},
number = {12},
abstract = { Growth inhibition and apoptotic/necrotic phenotype was observed in
nanogold particle (AuNP)-treated human chronic myelogenous leukemia
cells. To elucidate the underlying cellular mechanisms, proteomic
techniques including two-dimensional electrophoresis/mass spectrometry
and protein microarrays were utilized to study the differentially
expressed proteome and phosphoproteome, respectively. Systems biology
analysis of the proteomic data revealed that unfolded protein-associated
endoplasmic reticulum (ER) stress response was the predominant event.
Concomitant with transcriptomic analysis using mRNA expression, microarrays
show ER stress response in the AuNP-treated cells. The ER stress
protein markers’ expression assay unveiled AuNPs as an efficient
cellular ER stress elicitor. Upon ER stress, cellular responses,
including reactive oxygen species increase, mitochondrial cytochrome
c release, and mitochondria damage, chronologically occurred in the
AuNP-treated cells. Conclusively, this study demonstrates that AuNPs
cause cell death through induction of unmanageable ER stress. },
doi = {10.1021/nn2027775},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/nn2027775},
url = {http://pubs.acs.org/doi/abs/10.1021/nn2027775}
}
@ARTICLE{Tsangaris2006,
author = {Tsangaris, George T. And Kolialexi, Ageliki And Karamessinis, Panagiotis
M. And Anagnostopoulos, Athanasios K. And Antsaklis, Aris And Fountoulakis,
Michael And Mavrou, Ariadni},
title = {The Normal Human Amniotic Fluid Supernatant Proteome},
journal = {In Vivo},
year = {2006},
volume = {20},
pages = {479--490},
number = {4},
month = jul,
abstract = {Proteomic analysis combining two-dimentional electrophoresis (2DE)
and mass spectrometry (MS) has the potential for a wide range of
applications in biological and medical sciences, as protein screening
in tissues obtained from healthy and diseased conditions can determine
drug targets and diagnostic markers. Conventionally, amniotic fluid
(AF) samples are routinely used for prenatal diagnosis of a wide
range of fetal abnormalities. Proteomics have already been applied
in the analysis of tissues from fetuses with Down's syndrome, in
order to detect differences in their protein profile as compared
to the normal profiles and to determine possible diagnostic tools.
A detailed protein 2DE for the normal human AF has not been reported.
In the present study, the 2D protein database of the normal human
AF supernatant (AFS) was constructed. Ten AFS samples from women
carrying normal fetuses were analysed by 2DE. A mean of 412 spots
per gel were analyzed and protein identification was carried out
by MALDI-MS and MALDI-MS-MS. A 2D protein map comprising of 136 different
gene products was constructed. The majority of the identified proteins
are regulatory proteins, enzymes, secreted proteins, carriers and
immunoglobulins. Twelve hypothetical proteins were also included.
The normal AFS proteome map is a valuable tool for the study of aberrant
protein expression and the search for proteins as possible markers
for the prediction of abnormal fetuses.},
url = {http://iv.iiarjournals.org/cgi/content/abstract/20/4/479}
}
@ARTICLE{Tsao2011,
author = {Tsao, Douglas and Shabalina, Svetlana A. and Gauthier, Josee and
Dokholyan, Nikolay V. and Diatchenko, Luda},
title = {Disruptive mRNA folding increases translational efficiency of catechol-O-methyltransferase
variant},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {6201-6212},
number = {14},
abstract = {Catechol-O-methyltransferase (COMT) is a major enzyme controlling
catecholamine levels that plays a central role in cognition, affective
mood and pain perception. There are three common COMT haplotypes
in the human population reported to have functional effects, divergent
in two synonymous and one nonsynonymous position. We demonstrate
that one of the haplotypes, carrying the non-synonymous variation
known to code for a less stable protein, exhibits increased protein
expression in vitro. This increased protein expression, which would
compensate for lower protein stability, is solely produced by a synonymous
variation (C166T) situated within the haplotype and located in the
5' region of the RNA transcript. Based on mRNA secondary structure
predictions, we suggest that structural destabilization near the
start codon caused by the T allele could be related to the observed
increase in COMT expression. Our folding simulations of the tertiary
mRNA structures demonstrate that destabilization by the T allele
lowers the folding transition barrier, thus decreasing the probability
of occupying its native state. These data suggest a novel structural
mechanism whereby functional synonymous variations near the translation
initiation codon affect the translation efficiency via entropy-driven
changes in mRNA dynamics and present another example of stable compensatory
genetic variations in the human population.},
doi = {10.1093/nar/gkr165},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/14/6201.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/14/6201}
}
@ARTICLE{Tsapara2010,
author = {Tsapara, Anna and Luthert, Phillip and Greenwood, John and Hill,
Caroline S. and Matter, Karl and Balda, Maria S.},
title = {The RhoA Activator GEF-H1/Lfc Is a Transforming Growth Factor-{beta}
Target Gene and Effector That Regulates {alpha}-Smooth Muscle Actin
Expression and Cell Migration},
journal = {Mol. Biol. Cell},
year = {2010},
volume = {21},
pages = {860--870},
number = {6},
month = mar,
abstract = {Maintenance of the epithelial phenotype is crucial for tissue homeostasis.
In the retina, dedifferentiation and loss of integrity of the retinal
pigment epithelium (RPE) leads to retinal dysfunction and fibrosis.
Transforming growth factor (TGF)-{beta} critically contributes to
RPE dedifferentiation and induces various responses, including increased
Rho signaling, up-regulation of {alpha}-smooth muscle actin (SMA),
and cell migration and dedifferentiation. Cellular TGF-{beta} responses
are stimulated by different signal transduction pathways: some are
Smad dependent and others Smad independent. Alterations in Rho signaling
are crucial to both types of TGF-{beta} signaling, but how TGF-{beta}-stimulates
Rho signaling is poorly understood. Here, we show that primary RPE
cells up-regulated GEF-H1 in response to TGF-{beta}. GEF-H1 was the
only detectable Rho exchange factor increased by TGF-{beta}1 in a
genome-wide expression analysis. GEF-H1 induction was Smad4-dependant
and led to Rho activation. GEF-H1 inhibition counteracted {alpha}-SMA
up-regulation and cell migration. In patients with retinal detachments
and fibrosis, migratory RPE cells exhibited increased GEF-H1 expression,
indicating that induction occurs in diseased RPE in vivo. Our data
indicate that GEF-H1 is a target and functional effector of TGF-{beta}
by orchestrating Rho signaling to regulate gene expression and cell
migration, suggesting that it represents a new marker and possible
therapeutic target for degenerative and fibrotic diseases.},
url = {http://www.molbiolcell.org/cgi/content/abstract/21/6/860}
}
@ARTICLE{Tsaur2007,
author = {Tsaur, Grigory and Semenikhina, Elizaveta and Ivanova, Anna and Nasedkina,
Tatiana and Popov, Alexander and Shorikov, Egor and Saveliev, Leonid
and Fechina, Larisa},
title = {Molecular Remission in MLL/AF4-Positive Infant Leukemia Treated with
the All Trans-Retinoic Acid Based MLL-Baby Protocol.},
journal = {Blood (ASH Annual Meeting Abstracts)},
year = {2007},
volume = {110},
pages = {4254--},
number = {11},
month = nov,
abstract = {Statement. We recently developed a new treatment approach for infant
leukemia with MLL rearrangements (MLL-Baby) that consists of intermittent
pulses of all-trans retinoic acid (ATRA) and conventional chemotherapy.
Here, we present data on the molecular remission status of patients
with the MLL/AF4 rearrangement enrolled in this study. Materials
and methods. Six patients with MLL/AF4 rearrangement have been enrolled
in the MLL-Baby study in Ekaterinburg and Moscow since September
2003. Median age was 6.5 months (range 1.5-10 months). All have had
the BI immunophenotype. Leucocytes from bone marrow (BM) and peripheral
blood (PB) were obtained. Quality and integrity of RNA was estimated
using RNA 6000 Nano LabChip kit and 2100 Bioanalyzer (Agilent Technologies).
Only RNA with RNA integrity number more than 4.5 was taken further.
Qualitative PCR for MLL/AF4 fusion gene (FG) was performed either
by nested PCR (4 patients) (A. Borkhardt et al, 1994) or by low-density
biochips (2 patients). Conditions of qualitative real-time PCR (qRT-PCR)
for MLL-AF4 FG detection were previously described (J. Gabert et
al., 2003). {beta}2-microglobulin was used as the control gene. Normalized
copy number (NCN) of MLL/AF4 was calculated. Sensitivity of qRT-PCR
for BM specimens was 1x10-4 - 6x10-5, for PB was 1x10-4 - 7x10-4.
In accordance with the treatment design all patients were enrolled
on the high risk (HR) schedule as approved by Local and Federal Ethics
committees. Parents' informed consent was obtained. Results. We found
2 types of MLL/AF4 FG clearance. In 4 patients the elimination rate
of FG transcripts was very high. In this group FG could not be detected
after 1 course of ATRA that followed induction therapy or after HR
1 (I); in 1 patient with MLL/AF4, FG total clearance was achieved
after HR block 3 (VI) respectively; 1 patient currently under treatment
has few copies of MLL/AF4 after HR block 2 (V). There was no correlation
between the rate of elimination of MLL/AF4 FG with age, initial WBC
count or type of MLL/AF4 transcript. Once achieved, the molecular
remission in 5 patients has remained PCR negative. Conclusions. Achievement
of molecular remission is one of the most important steps toward
long-term survival and cure. Despite differences in the rate of elimination
of MLL/AF4 FG, 5 of 6 patients treated on the MLL-Baby protocol have
remained in hematological and molecular remission with a median follow-up
18 months (range 6-45 months). None have relapsed. Moreover, the
youngest patient, a girl who was 2 months old at the time of diagnosis,
has had the longest continuous molecular remission of up to 45 months.
The 6th patient has single copies of MLL/AF4 after HR block 2 (V)
and is currently receiving therapy.},
url = {http://abstracts.hematologylibrary.org/cgi/content/abstract/110/11/4254}
}
@ARTICLE{Tseng2006,
author = {Tseng, Hsiang-Wen and Juan, Hsueh-Fen and Huang, Hsuan-Cheng and
Lin, John Yi-Chung and Sinchaikul, Supachok and Lai, Tzi-Chung and
Chen, Chieh-Fu and Chen, Shui-Tein and Wang, Guei-Jane},
title = {Lipopolysaccharide-stimulated responses in rat aortic endothelial
cells by a systems biology approach},
journal = {Proteomics},
year = {2006},
volume = {6},
pages = {5915--5928},
number = {22},
abstract = {Abstract The vascular endothelium plays an important role in regulating
immune and inflammatory responses to resist pathogens infection.
Although it has been known that lipopolysaccharide (LPS) is a critical
inducer of sepsis or endotoxemia, the systematic responses of LPS-stimulation
in endothelial cells (ECs) are still unclear. The present study aims
to analyze the late-phase responses of LPS-induced rat aortic ECs
by using systematic biology approaches, including rat cDNA microarray,
2-DE and MALDI-TOF MS/MS, and cytokine protein array. Furthermore,
to improve the efficiency of analysis of the bulk systematic data
of rat, we designed a set of bioinformatic tools to convert and integrate
these rat data into the corresponding human genes or proteins IDs
based on BioCarta, KEGG, and Gene Ontology databases. Using the systematic
analysis, it was shown that LPS could promote some signaling or metabolic
pathways as well as pathophysiologic phenomena of proliferation,
atherogenesis, inflammation, and apoptosis through activated nuclear
factor-κB pathway in ECs. Interestingly, ECs also activated the
mediators of anti-inflammation, antiapoptosis, and antioxidation
to protect themselves. Moreover, the expressions of altered genes,
proteins, and their involvement in the hypothetical signaling pathway
can provide further understanding of inflammation associated responses
in ECs.},
issn = {1615-9861},
keywords = {Endothelial cells, Inflammation, Lipopolysaccharide, Systems biology},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200600296}
}
@ARTICLE{Tserel2010,
author = {Tserel, Liina and Kolde, Raivo and Rebane, Ana and Kisand, Kai and
Org, Tõnis and Peterson, Hedi and Vilo, Jaak and Peterson, Pärt},
title = {Genome-wide promoter analysis of histone modifications in human monocyte-derived
antigen presenting cells},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {642},
number = {1},
abstract = {BACKGROUND:Monocyte-derived macrophages and dendritic cells (DCs)
are important in inflammatory processes and are often used for immunotherapeutic
approaches. Blood monocytes can be differentiated into macrophages
and DCs, which is accompanied with transcriptional changes in many
genes, including chemokines and cell surface markers.RESULTS:To study
the chromatin modifications associated with this differentiation,
we performed a genome wide analysis of histone H3 trimethylation
on lysine 4 (H3K4me3) and 27 (H3K27me3) as well as acetylation of
H3 lysines (AcH3) in promoter regions. We report that both H3K4me3
and AcH3 marks significantly correlate with transcriptionally active
genes whereas H3K27me3 mark is associated with inactive gene promoters.
During differentiation, the H3K4me3 levels decreased on monocyte-specific
CD14, CCR2 and CX3CR1 but increased on DC-specific TM7SF4/DC-STAMP,
TREM2 and CD209/DC-SIGN genes. Genes associated with phagocytosis
and antigen presentation were marked by H3K4me3 modifications. We
also report that H3K4me3 levels on clustered chemokine and surface
marker genes often correlate with transcriptional activity.CONCLUSION:Our
results provide a basis for further functional correlations between
gene expression and histone modifications in monocyte-derived macrophages
and DCs.},
doi = {10.1186/1471-2164-11-642},
issn = {1471-2164},
pubmedid = {21087476},
url = {http://www.biomedcentral.com/1471-2164/11/642}
}
@ARTICLE{Tserel2011,
author = {Tserel, Liina and Runnel, Toomas and Kisand, Kai and Pihlap, Maire
and Bakhoff, Lairi and Kolde, Raivo and Peterson, Hedi and Vilo,
Jaak and Peterson, Part and Rebane, Ana},
title = {MicroRNA Expression Profiles of Human Blood Monocyte-derived Dendritic
Cells and Macrophages Reveal miR-511 as Putative Positive Regulator
of Toll-like Receptor 4},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {26487-26495},
number = {30},
abstract = {Dendritic cells (DCs) and macrophages (MFs) are important multifunctional
immune cells. Like other cell types, they express hundreds of different
microRNAs (miRNAs) that are recently discovered post-transcriptional
regulators of gene expression. Here we present updated miRNA expression
profiles of monocytes, DCs and MFs. Compared with monocytes, [~]50
miRNAs were found to be differentially expressed in immature and
mature DCs or MFs, with major expression changes occurring during
the differentiation. Knockdown of DICER1, a protein needed for miRNA
biosynthesis, led to lower DC-specific intercellular adhesion molecule-3-grabbing
non-integrin (DC-SIGN) and enhanced CD14 protein levels, confirming
the importance of miRNAs in DC differentiation in general. Inhibition
of the two most highly up-regulated miRNAs, miR-511 and miR-99b,
also resulted in reduced DC-SIGN level. Prediction of miRNA-511 targets
revealed a number of genes with known immune functions, of which
TLR4 and CD80 were validated using inhibition of miR-511 in DCs and
luciferase assays in HEK293 cells. Interestingly, under the cell
cycle arrest conditions, miR-511 seems to function as a positive
regulator of TLR4. In conclusion, we have identified miR-511 as a
novel potent modulator of human immune response. In addition, our
data highlight that miRNA influence on gene expression is dependent
on the cellular environment.},
doi = {10.1074/jbc.M110.213561},
eprint = {http://www.jbc.org/cgi/reprint/286/30/26487.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/30/26487}
}
@ARTICLE{Tseveleki2010,
author = {Tseveleki, Vivian and Rubio, Renee and Vamvakas, Sotiris-Spyros and
White, Joseph and Taoufik, Era and Petit, Edwige and Quackenbush,
John and Probert, Lesley},
title = {Comparative gene expression analysis in mouse models for multiple
sclerosis, Alzheimer's disease and stroke for identifying commonly
regulated and disease-specific gene changes},
journal = {Genomics},
year = {2010},
volume = {96},
pages = {82--91},
number = {2},
month = aug,
abstract = {The brain responds to injury and infection by activating innate defense
and tissue repair mechanisms. Working upon the hypothesis that the
brain defense response involves common genes and pathways across
diverse pathologies, we analysed global gene expression in brain
from mouse models representing three major central nervous system
disorders, cerebral stroke, multiple sclerosis and Alzheimer's disease
compared to normal brain using DNA microarray expression profiling.
A comparison of dysregulated genes across disease models revealed
common genes and pathways including key components of estrogen and
TGF-[beta] signaling pathways that have been associated with neuroprotection
as well as a neurodegeneration mediator, TRPM7. Further, for each
disease model, we discovered collections of differentially expressed
genes that provide novel insight into the individual pathology and
its associated mechanisms. Our data provide a resource for exploring
the complex molecular mechanisms that underlie brain neurodegeneration
and a new approach for identifying generic and disease-specific targets
for therapy.},
issn = {0888-7543},
keywords = {cDNA microarrays, Brain inflammation, Cerebral stroke, Alzheimer's
disease, Systems biology, Gene expression profiling},
url = {http://www.sciencedirect.com/science/article/B6WG1-4YYXJMJ-1/2/378fce0e15b26acb9a2c8e74a44571ae}
}
@ARTICLE{Tsika2010,
author = {Tsika, Richard W. and Ma, Lixin and Kehat, Izhak and Schramm, Christine
and Simmer, Gretchen and Morgan, Brandon and Fine, Deborah M. and
Hanft, Laurin M. and McDonald, Kerry S. and Molkentin, Jeffery D.
and Krenz, Maike and Yang, Steve and Ji, Juan},
title = {TEAD-1 Overexpression in the Mouse Heart Promotes an Age-dependent
Heart Dysfunction},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {13721--13735},
number = {18},
month = apr,
abstract = {TEA domain transcription factor-1 (TEAD-1) is essential for proper
heart development and is implicated in cardiac specific gene expression
and the hypertrophic response of primary cardiomyocytes to hormonal
and mechanical stimuli, and its activity increases in the pressure-overloaded
hypertrophied rat heart. To investigate whether TEAD-1 is an in vivo
modulator of cardiac specific gene expression and hypertrophy, we
developed transgenic mice expressing hemagglutinin-tagged TEAD-1
under the control of the muscle creatine kinase promoter. We show
that a sustained increase in TEAD-1 protein leads to an age-dependent
dysfunction. Magnetic resonance imaging revealed decreases in cardiac
output, stroke volume, ejection fraction, and fractional shortening.
Isolated TEAD-1 hearts revealed decreased left ventricular power
output that correlated with increased {beta}MyHC protein. Histological
analysis showed altered alignment of cardiomyocytes, septal wall
thickening, and fibrosis, although electrocardiography displayed
a left axis shift of mean electrical axis. Transcripts representing
most members of the fetal heart gene program remained elevated from
fetal to adult life. Western blot analyses revealed decreases in
p-phospholamban, SERCA2a, p-CX43, p-GSK-3{alpha}/{beta}, nuclear
{beta}-catenin, GATA4, NFATc3/c4, and increased NCX1, nuclear DYKR1A,
and Pur{alpha}/{beta} protein. TEAD-1 mice did not display cardiac
hypertrophy. TEAD-1 mice do not tolerate stress as they die over
a 4-day period after surgical induction of pressure overload. These
data provide the first in vivo evidence that increased TEAD-1 can
induce characteristics of cardiac remodeling associated with cardiomyopathy
and heart failure.},
url = {http://www.jbc.org/cgi/content/abstract/285/18/13721}
}
@ARTICLE{Tsika2008,
author = {Tsika, Richard W. and Schramm, Christine and Simmer, Gretchen and
Fitzsimons, Daniel P. and Moss, Richard L. and Ji, Juan},
title = {Overexpression of TEAD-1 in Transgenic Mouse Striated Muscles Produces
a Slower Skeletal Muscle Contractile Phenotype},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {36154--36167},
number = {52},
month = dec,
abstract = {TEA domain (TEAD) transcription factors serve important functional
roles during embryonic development and in striated muscle gene expression.
Our previous work has implicated a role for TEAD-1 in the fast-to-slow
fiber-type transition in response to mechanical overload. To investigate
whether TEAD-1 is a modulator of slow muscle gene expression in vivo,
we developed transgenic mice expressing hemagglutinin (HA)-tagged
TEAD-1 under the control of the muscle creatine kinase promoter.
We show that striated muscle-restricted HA-TEAD-1 expression induced
a transition toward a slow muscle contractile protein phenotype,
slower shortening velocity (Vmax), and longer contraction and relaxation
times in adult fast twitch extensor digitalis longus muscle. Notably,
HA-TEAD-1 overexpression resulted in an unexpected activation of
GSK-3{alpha}/{beta} and decreased nuclear {beta}-catenin and NFATc1/c3
protein. These effects could be reversed in vivo by mechanical overload,
which decreased muscle creatine kinase-driven TEAD-1 transgene expression,
and in cultured satellite cells by TEAD-1-specific small interfering
RNA. These novel in vivo data support a role for TEAD-1 in modulating
slow muscle gene expression.},
url = {http://www.jbc.org/cgi/content/abstract/283/52/36154}
}
@ARTICLE{Tsinkalovsky2005,
author = {Tsinkalovsky, Oleg and Rosenlund, Benedikte and Laerum, Ole Didrik
and Eiken, Hans Geir},
title = {Clock gene expression in purified mouse hematopoietic stem cells},
journal = {Experimental Hematology},
year = {2005},
volume = {33},
pages = {100--107},
number = {1},
month = jan,
abstract = {Objective Circadian genes have recently been characterized in many
tissues, but not in hematopoietic stem cells. These cells are rare
in the bone marrow (BM), which makes it difficult to collect enough
cells for detailed molecular analysis in a short period of time without
reduced RNA quality. The aim was to improve methodology and reliability
of clock gene expression analysis in purified mouse hematopoietic
stem cells.Methods Stem cells were highly enriched by high-speed
flow cytometric cell sorting of the side population (SP) cells from
Hoechst 33342 (Hoechst)-stained mouse BM. Total RNA was isolated
from sorted SP and whole BM cells and exposed to DNase treatment.
The relative mRNA levels of major clock genes mPer1, mPer2, mBmal1,
mCry1, mClock, and mRev-erb [alpha] were measured with real-time
quantitative reverse transcription polymerase chain reaction (Q-RT-PCR)
and normalized to m36B4, used as a reference gene. The clonogenity
of sorted SP cells and whole BM; cells taken before and after sorting,
were tested in colony-formation assay.Results Clock gene activity
in sorted SP cells showed pronounced relative differences compared
with whole BM for mPer1 and mCry1. The high-speed sorting procedure
did not influence clock gene expression or cell clonogenity, even
when this was performed with a delay period up to 24 hours.Conclusions
We demonstrated expression of six clock genes in mouse hematopoietic
stem cells. A combination of high-speed flow cytometric sorting and
Q-RT-PCR was shown to be useful and reliable for analysis of clock
gene activity in small stem cell fractions.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4F8SXDF-D/2/9835e3c2f757bf6c1bee3c4bc664e5f1}
}
@ARTICLE{Tsinkalovsky2007,
author = {Tsinkalovsky, Oleg and Smaaland, Rune and Rosenlund, Benedikte and
Sothern, Robert B. and Hirt, Asle and Steine, Solrun and Badiee,
Azadeh and Foss Abrahamsen, Jenny and Eiken, Hans Geir and Laerum,
Ole Didrik},
title = {Circadian Variations in Clock Gene Expression of Human Bone Marrow
CD34+ Cells},
journal = {J Biol Rhythms},
year = {2007},
volume = {22},
pages = {140--150},
number = {2},
month = apr,
abstract = {Time-dependent variations in clock gene expression have recently been
observed in mouse hematopoietic cells, but the activity of these
genes in human bone marrow (BM) has so far not been investigated.
Since such data can be of considerable clinical interest for monitoring
the dynamics in stem/progenitor cells, the authors have studied mRNA
expression of the clock genes hPer1 , hPer2, hCry1, hCry2, hBmal1,
hRev-erb {alpha}, and hClock in human hematopoietic CD34-positive
(CD34 +) cells. CD34+ cells were isolated from the BM samples obtained
from 10 healthy men at 6 times over 24 h. In addition, clock gene
mRNA expression was analyzed in the whole BM in 3 subjects. Rhythms
in serum cortisol, growth hormone, testosterone, and leukocyte counts
documented that subjects exhibited standardized circadian patterns.
All 7 clock genes were expressed both in CD34+ cells and the whole
BM, with some differences in magnitude between the 2 cell populations.
A clear circadian rhythm was shown for hPer1, hPer2, and hCry2 expression
in CD34+ cells and for hPer1 in the whole BM, with maxima from early
morning to midday. Similar to mouse hematopoietic cells, h Bmal1
was not oscillating rhythmically. The study demonstrates that clock
gene expression in human BM stem/progenitor cells may be developmentally
regulated, with strong or weaker circadian profiles as compared to
those reported in other mature tissues.},
url = {http://jbr.sagepub.com/cgi/content/abstract/22/2/140}
}
@ARTICLE{Tsitsiou2012,
author = {Eleni Tsitsiou and Andrew E. Williams and Sterghios A. Moschos and
Ketan Patel and Christos Rossios and Xiaoying Jiang and Oona-Delpuech
Adams and Patricia Macedo and Richard Booton and David Gibeon and
Kian Fan Chung and Mark A. Lindsay},
title = {Transcriptome analysis shows activation of circulating CD8+ T cells
in patients with severe asthma},
journal = {Journal of Allergy and Clinical Immunology},
year = {2012},
volume = {129},
pages = {95 - 103},
number = {1},
abstract = {Background Although previous studies have implicated tissue CD4+ T
cells in the development and maintenance of the inflammatory response
in asthmatic patients, little is known about the role of CD8+ T cells.
There is now accumulating evidence that microRNAs and other noncoding
RNAs are important regulators of T-cell function. Objectives We sought
to use transcriptomics to determine the activation state of circulating
CD4+ and CD8+ T cells in patients with nonsevere and severe asthma.
Methods mRNA and noncoding RNA expression in circulating T cells
was measured by means of microarray, quantitative real-time PCR,
or both. Results Comparison of mRNA expression showed widespread
changes in the circulating CD8+ but not CD4+ T cells from patients
with severe asthma. No changes were observed in the CD4+ and CD8+
T cells in patients with nonsevere asthma versus those in healthy
control subjects. Bioinformatics analysis showed that the changes
in CD8+ T-cell mRNA expression were associated with multiple pathways
involved in T-cell activation. As with mRNAs, we also observed widespread
changes in expression of noncoding RNA species, including natural
antisense, pseudogenes, intronic long noncoding RNAs (lncRNAs), and
intergenic lncRNAs in CD8+ T cells from patients with severe asthma.
Measurement of the microRNA expression profile showed selective downregulation
of miR-28-5p in CD8+ T cells and reduction of miR-146a and miR-146b
in both CD4+ and CD8+ T cells. Conclusions Severe asthma is associated
with the activation of circulating CD8+ T cells but not CD4+ T cells.
This response is correlated with the downregulation of miR-146a/b
and miR-28-5p, as well as changes in the expression of multiple species
of lncRNA that might regulate CD8+ T-cell function.},
doi = {10.1016/j.jaci.2011.08.011},
issn = {0091-6749},
keywords = {Severe asthma},
url = {http://www.sciencedirect.com/science/article/pii/S0091674911013108}
}
@ARTICLE{Tsubota2010,
author = {Tsubota, Akihito and Matsumoto, Kenji and Mogushi, Kaoru and Nariai,
Koichi and Namiki, Yoshihisa and Hoshina, Sadayori and Hano, Hiroshi
and Tanaka, Hiroshi and Saito, Hirohisa and Tada, Norio},
title = {IQGAP1 and vimentin are key regulator genes in naturally occurring
hepatotumorigenesis induced by oxidative stress},
journal = {Carcinogenesis},
year = {2010},
volume = {31},
pages = {504--511},
number = {3},
month = mar,
abstract = {To identify key genes involved in the complex multistep process of
hepatotumorigenesis, we reduced multivariate clinicopathological
variables by using the Long-Evans Cinnamon rat, a model with naturally
occurring and oxidative stress-induced hepatotumorigenesis. Gene
expression patterns were analyzed serially by profiling liver tissues
from rats of a naive status (4 weeks old), through to those with
chronic hepatitis (26 and 39 weeks old) to tumor development (67
weeks old). Of 31 099 probe sets used for microarray analysis, 87
were identified as being upregulated in a stepwise manner during
disease progression and tumor development. Quantitative real-time
reverse transcription-polymerase chain reaction and statistical analyses
verified that IQGAP1 and vimentin mRNA expression levels increased
significantly throughout hepatotumorigenesis. A hierarchical clustering
algorithm showed both genes clustered together and in the same cluster
group. Immunohistochemical and western blot analyses showed similar
increases in protein levels of IAGAP1 and vimentin. Finally, pathway
analyses using text-mining technology with more comprehensive and
recent gene-gene interaction data identified IQGAP1 and vimentin
as important nodes in underlying gene regulatory networks. These
findings enhance our understanding of the multistep hepatotumorigenesis
and identification of target molecules for novel treatments.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/31/3/504}
}
@ARTICLE{Tsuchida2009,
author = {Tsuchida, Takayuki and Miyamoto, Tatsuya and Yamagishi, Takashi and
Kira, Satoru and Kayanuma, Kenji and Haneda, Yaburu and Kobayashi,
Hideki and Zakoji, Hidenori and Araki, Isao and Takeda, Masayuki},
title = {The effect of chinese herbal medicine containing aconitine on the
pain relief in interstitial cystitis patients. - a preliminary study
-},
journal = {The Journal of Urology},
year = {2009},
volume = {181},
pages = {23--24},
number = {4, Supplement 1},
month = apr,
booktitle = {AUA Annual Meeting Program Abstracts, 2009 AUA Annual Meeting},
issn = {0022-5347},
url = {http://www.sciencedirect.com/science/article/B7XMT-4VTWN64-2F/2/2e17382e9ae98c4a62f3e8d0bfa1bb57}
}
@ARTICLE{Tsuchihara2009,
author = {Tsuchihara, Katsuya and Suzuki, Yutaka and Wakaguri, Hiroyuki and
Irie, Takuma and Tanimoto, Kousuke and Hashimoto, Shin-ichi and Matsushima,
Kouji and Mizushima-Sugano, Junko and Yamashita, Riu and Nakai, Kenta
and Bentley, David and Esumi, Hiroyasu and Sugano, Sumio},
title = {Massive transcriptional start site analysis of human genes in hypoxia
cells},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {2249--2263},
number = {7},
month = apr,
abstract = {Combining our full-length cDNA method and the massively parallel sequencing
technology, we developed a simple method to collect precise positional
information of transcriptional start sites (TSSs) together with digital
information of the gene-expression levels in a high throughput manner.
We applied this method to observe gene-expression changes in a colon
cancer cell line cultured in normoxic and hypoxic conditions. We
generated more than 100 million 36-base TSS-tag sequences and revealed
comprehensive features of hypoxia responsive alterations in the transcriptional
landscape of the human genome. The features include presence of inducible
hot regions' in 54 genomic regions, 220 novel hypoxia inducible promoters
that may drive non-protein-coding transcripts, 191 hypoxia responsive
alternative promoters and detailed views of 120 novel as well as
known hypoxia responsive genes. We further analyzed hypoxic response
of different cells using additional 60 million TSS-tags and found
that the degree of the gene-expression changes were different among
cell lines, possibly reflecting cellular robustness against hypoxia.
The novel dynamic figure of the human gene transcriptome will deepen
our understanding of the transcriptional program of the human genome
as well as bringing new insights into the biology of cancer cells
in hypoxia.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/7/2249}
}
@ARTICLE{Tsuchiya2011,
author = {Hiroyoshi Tsuchiya and Kentarou Ushijima and Yoko Fujiwara and Akio
Fujimura and Taka-aki Koshimizu},
title = {Chronic ritodrine treatment induces refractoriness of glucose-lowering
β2 adrenoceptor signal in female mice},
journal = {Regulatory Toxicology and Pharmacology},
year = {2011},
pages = { - },
number = {0},
abstract = {Adverse events in tocolytic therapy with β2-adrenergic agents compromise
cardiovascular and non-cardiovascular functions, including blood
glucose regulation and liver function. Here, we have examined the
effects of the β2 agonist ritodrine on glucose metabolism and liver
injury in mice. Under fasting conditions, ritodrine significantly
increased serum insulin levels and decreased glucose concentrations.
This contrasts with the β2 agonist-induced hyperglycemia observed
in previous studies on humans and other animals. After 14 days
of ritodrine treatment, the mice showed a decrease in the total mass
of epididymal fat pads, whereas their body weights increased significantly.
Chronic ritodrine treatment attenuated the glucose-lowering effect
observed during acute administration. Ritodrine also significantly
increased serum levels of liver enzymes, which returned to control
levels after 14 days of treatment. Thus, ritodrine responsiveness
changes between acute and chronic treatment, indicating that close
monitoring of blood glucose and serum liver enzymes is necessary
in patients with reduced glucose tolerance. The findings reported
here of glucose homeostasis in mice provide a unique opportunity
to understand refractoriness of β2-adrenoceptor signaling in response
to β2 agonists during the course of treatment.},
doi = {10.1016/j.yrtph.2011.11.011},
issn = {0273-2300},
keywords = {β2-Adrenergic receptor},
url = {http://www.sciencedirect.com/science/article/pii/S0273230011002406}
}
@ARTICLE{Tsuchiya2008,
author = {Tsuchiya, Masato and Kono, Hiroshi and Matsuda, Masanori and Fujii,
Hideki and Rusyn, Ivan},
title = {Protective effect of Juzen-taiho-to on hepatocarcinogenesis is mediated
through the inhibition of Kupffer cell-induced oxidative stress},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {2503--2511},
number = {11},
abstract = {Abstract 10.1002/ijc.23828.abs Traditional herbal formulations, such
as Juzen-taiho-to (TJ-48), are used extensively in medical practice
in Asia even though their mechanism of action remains elusive. This
study tested a hypothesis that TJ-48 is protective against hepatocarcinogenesis
by impeding Kupffer cell-induced oxidative stress. Forty-eight patients
were randomly assigned to receive TJ-48 (n = 10), or no supplementation
(n = 38) for up to 6 years after surgical treatment for hepatocellular
carcinoma (HCC). In addition, to investigate the mechanism of protective
action of TJ-48, diethylnitrosamine-containing water was administered
for 22 weeks to male mice that were fed regular chow or TJ-48-containing
diet. Liver tumor incidence, cell proliferation, number of 8-hydroxy-2′-deoxyguanosine-
or F4/80-positive cells, and cytokine expression were evaluated.
Although most of the patients experienced recurrence of HCC, a significantly
longer intrahepatic recurrence-free survival was observed in the
TJ-48 group. In mice, TJ-48 inhibited the development of liver tumors,
reduced oxidative DNA damage, inflammatory cell infiltration and
cytokine expression. Administration of TJ-48 improves intrahepatic
recurrence-free survival after surgical treatment of hepatocellular
carcinoma. On the basis of animal experiments, we reason that the
protective mechanism of TJ-48 involves inhibition of Kupffer cells.
This leads to lower levels of pro-inflammatory cytokines and oxidants
in liver which may slow down the process of hepatocarcinogenesis
and improves hepatic recurrence-free survival in patients with HCC.
© 2008 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {TJ-48, hepatocellular carcinoma, Kupffer cell, intrahepatic recurrence-free
survival},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23828}
}
@ARTICLE{Tsuchiya2009,
author = {Tsuchiya, Soken and Tachida, Yuki and Segi-Nishida, Eri and Okuno,
Yasushi and Tamba, Shigero and Tsujimoto, Gozoh and Tanaka, Satoshi
and Sugimoto, Yukihiko},
title = {Characterization of gene expression profiles for different types
of mast cells pooled from mouse stomach subregions by an RNA amplification
method},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {35},
number = {1},
abstract = {BACKGROUND:Mast cells (MCs) play pivotal roles in allergy and innate
immunity and consist of heterogenous subclasses. However, the molecular
basis determining the different characteristics of these multiple
MC subclasses remains unclear.RESULTS:To approach this, we developed
a method of RNA extraction/amplification for intact in vivo MCs pooled
from frozen tissue sections, which enabled us to obtain the global
gene expression pattern of pooled MCs belonging to the same subclass.
MCs were isolated from the submucosa (sMCs) and mucosa (mMCs) of
mouse stomach sections, respectively, 15 cells were pooled, and their
RNA was extracted, amplified and subjected to microarray analysis.
Known marker genes specific for mMCs and sMCs showed expected expression
trends, indicating accuracy of the analysis.We identified 1,272 genes
showing significantly different expression levels between sMCs and
mMCs, and classified them into clusters on the basis of similarity
of their expression profiles compared with bone marrow-derived MCs,
which are the cultured MCs with so-called 'immature' properties.
Among them, we found that several key genes such as Notch4 had sMC-biased
expression and Ptgr1 had mMC-biased expression. Furthermore, there
is a difference in the expression of several genes including extracellular
matrix protein components, adhesion molecules, and cytoskeletal proteins
between the two MC subclasses, which may reflect functional adaptation
of each MC to the mucosal or submucosal environment in the stomach.CONCLUSION:By
using the method of RNA amplification from pooled intact MCs, we
characterized the distinct gene expression profiles of sMCs and mMCs
in the mouse stomach. Our findings offer insight into possible unidentified
properties specific for each MC subclass.},
doi = {10.1186/1471-2164-10-35},
issn = {1471-2164},
pubmedid = {19154611},
url = {http://www.biomedcentral.com/1471-2164/10/35}
}
@ARTICLE{Tsui2011,
author = {Tsui, Kyle and Dubuis, Sebastien and Gebbia, Marinella and Morse,
Randall H. and Barkai, Naama and Tirosh, Itay and Nislow, Corey},
title = {Evolution of Nucleosome Occupancy: Conservation of Global Properties
and Divergence of Gene-Specific Patterns},
journal = {Mol. Cell. Biol.},
year = {2011},
volume = {31},
pages = {4348-4355},
number = {21},
abstract = {To examine the role of nucleosome occupancy in the evolution of gene
expression, we measured the genome-wide nucleosome profiles of four
yeast species, three belonging to the Saccharomyces sensu stricto
lineage and the more distantly related Candida glabrata. Nucleosomes
and associated promoter elements at C. glabrata genes are typically
shifted upstream by [~]20 bp, compared to their orthologs from sensu
stricto species. Nonetheless, all species display the same global
organization features first described for Saccharomyces cerevisiae:
a stereotypical nucleosome organization along genes and a division
of promoters into those that contain or lack a pronounced nucleosome-depleted
region (NDR), with the latter displaying a more dynamic pattern of
gene expression. Despite this global similarity, however, nucleosome
occupancy at specific genes diverged extensively between sensu stricto
and C. glabrata orthologs ([~]50 million years). Orthologs with dynamic
expression patterns tend to maintain their lack of NDR, but apart
from that, sensu stricto and C. glabrata orthologs are nearly as
similar in nucleosome occupancy patterns as nonorthologous genes.
This extensive divergence in nucleosome occupancy contrasts with
a conserved pattern of gene expression. Thus, while some evolutionary
changes in nucleosome occupancy contribute to gene expression divergence,
nucleosome occupancy often diverges extensively with apparently little
impact on gene expression.},
doi = {10.1128/MCB.05276-11},
eprint = {http://mcb.asm.org/cgi/reprint/31/21/4348.pdf},
url = {http://mcb.asm.org/cgi/content/abstract/31/21/4348}
}
@ARTICLE{Tsukamoto2011,
author = {Tsukamoto, Shunsuke and Ishikawa, Toshiaki and Iida, Satoru and Ishiguro,
Megumi and Mogushi, Kaoru and Mizushima, Hiroshi and Uetake, Hiroyuki
and Tanaka, Hiroshi and Sugihara, Kenichi},
title = {Clinical Significance of Osteoprotegerin Expression in Human Colorectal
Cancer},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {2444--2450},
number = {8},
month = apr,
abstract = {Purpose: This study aimed to identify a novel biomarker or a target
of treatment for colorectal cancer (CRC). Experimental Design: The
expression profiles of cancer cells in 104 patients with CRC were
examined using laser microdissection and oligonucleotide microarray
analysis. Overexpression in CRC cells, especially in patients with
distant metastases, was a prerequisite to select candidate genes.
The mRNA expression of candidate genes was investigated by quantitative
reverse transcriptase PCR (RT-PCR) in 77 patients as a validation
study. We analyzed the protein expression and localization of the
candidate gene by immunohistochemical study and investigated the
relationship between protein expression and clinicopathologic features
in 274 CRC patients. Results: Using microarray analysis, we identified
6 candidate genes related to distant metastases in CRC patients.
Among these genes, osteoprotegerin (OPG) is known to be associated
with aggressiveness in several cancers through inhibition of apoptosis
via neutralization of the function of TNF-related apoptosis-inducing
ligand. The mRNA expression of OPG in cancer tissues was significantly
higher in patients with distant metastases than those without metastases.
Overexpression of OPG protein was associated with significantly worse
overall survival and relapse-free survival. Moreover, overexpression
of the OPG protein was an independent risk factor for CRC recurrence.
Conclusion: Overexpression of OPG may be a predictive biomarker of
CRC recurrence and a target for treatment of this disease. Clin Cancer
Res; 17(8); 2444-50. (C)2011 AACR.},
comment = {10.1158/1078-0432.CCR-10-2884},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/8/2444}
}
@ARTICLE{Tsukue2010,
author = {Tsukue, Naomi and Okumura, Hiroki and Ito, Tsuyoshi and Sugiyama,
Gen and Nakajima, Toru},
title = {Toxicological evaluation of diesel emissions on A549 cells},
journal = {Toxicology in Vitro},
year = {2010},
volume = {24},
pages = {363--369},
number = {2},
month = mar,
abstract = {To evaluate the health effects of diesel emissions (DE) using an in
vitro experiment, A549 cells were exposed to emission from a diesel
engine on an engine dynamo, using a culture-cell-exposure device.
Three groups were set according to cell exposure to high concentrations
of particulate matter (PM) and/or nitrogen dioxide (NO2). The emissions
of each group was dilution rate 1:100 and 1:10, and PM was 0.8 mg/m3
and/or NO2 was 80 ppm at dilution rate 1:10. After 1 h, exposed cells
were analyzed for cell viability and gene expression. Fifty percent
of cell viability in the high-PM/high-NO2 exposure group occurred
at a dilution rate of 1:14, based on the concentration of CO2. Heme
oxygenase-1 mRNA expression significantly increased at 1:100 dilution
of the high-PM/high-NO2 group and 1:100 and 1:10 dilutions of the
high-PM/low-NO2 group, compared to background air. By DNA microarray,
all gene expressions at a dilution rate of 1:10 in each group were
observed to be higher than those at 1:100, and some cancer-related
genes up-regulated. We concluded that screening methods for evaluating
health effects could be established using this cell-exposure system
because the effects of DE on A549 cells were shown by cell viability
and gene expression.},
issn = {0887-2333},
keywords = {Diesel emissions, CULTEX, A549, In vitro, Exposure},
url = {http://www.sciencedirect.com/science/article/B6TCP-4XNF41R-1/2/ffb7b93dfb9b496eb4844469bb1c9a3f}
}
@ARTICLE{Tsumagari2011,
author = {Tsumagari, Koji and Chang, Shao-Chi and Lacey, Michelle and Baribault,
Carl and Chittur, Sridar and Sowden, Janet and Tawil, Rabi and Crawford,
Gregory and Ehrlich, Melanie},
title = {Gene expression during normal and FSHD myogenesis},
journal = {BMC Medical Genomics},
year = {2011},
volume = {4},
pages = {67},
number = {1},
abstract = {BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is a dominant
disease linked to contraction of an array of tandem 3.3-kb repeats
(D4Z4) at 4q35. Within each repeat unit is a gene, DUX4, that can
encode a protein containing two homeodomains. A DUX4 transcript derived
from the last repeat unit in a contracted array is associated with
pathogenesis but it is unclear how.METHODS:Using exon-based microarrays,
the expression profiles of myogenic precursor cells were determined.
Both undifferentiated myoblasts and myoblasts differentiated to myotubes
derived from FSHD patients and controls were studied after immunocytochemical
verification of the quality of the cultures. To further our understanding
of FSHD and normal myogenesis, the expression profiles obtained were
compared to those of 19 non-muscle cell types analyzed by identical
methods.RESULTS:Many of the ~17,000 examined genes were differentially
expressed (> 2-fold, p < 0.01) in control myoblasts or myotubes vs.
non-muscle cells (2185 and 3006, respectively) or in FSHD vs. control
myoblasts or myotubes (295 and 797, respectively). Surprisingly,
despite the morphologically normal differentiation of FSHD myoblasts
to myotubes, most of the disease-related dysregulation was seen as
dampening of normal myogenesis-specific expression changes, including
in genes for muscle structure, mitochondrial function, stress responses,
and signal transduction. Other classes of genes, including those
encoding extracellular matrix or pro-inflammatory proteins, were
upregulated in FSHD myogenic cells independent of an inverse myogenesis
association. Importantly, the disease-linked DUX4 RNA isoform was
detected by RT-PCR in FSHD myoblast and myotube preparations only
at extremely low levels. Unique insights into myogenesis-specific
gene expression were also obtained. For example, all four Argonaute
genes involved in RNA-silencing were significantly upregulated during
normal (but not FSHD) myogenesis relative to non-muscle cell types.CONCLUSIONS:DUX4's
pathogenic effect in FSHD may occur transiently at or before the
stage of myoblast formation to establish a cascade of gene dysregulation.
This contrasts with the current emphasis on toxic effects of experimentally
upregulated DUX4 expression at the myoblast or myotube stages. Our
model could explain why DUX4's inappropriate expression was barely
detectable in myoblasts and myotubes but nonetheless linked to FSHD.},
doi = {10.1186/1755-8794-4-67},
issn = {1755-8794},
pubmedid = {21951698},
url = {http://www.biomedcentral.com/1755-8794/4/67}
}
@ARTICLE{Tsuru2011,
author = {Tsuru, Saburo and Yasuda, Nao and Murakami, Yoshie and Ushioda, Junya
and Kashiwagi, Akiko and Suzuki, Shingo and Mori, Kotaro and Ying,
Bei-Wen and Yomo, Tetsuya},
title = {Adaptation by stochastic switching of a monostable genetic circuit
in Escherichia coli},
journal = {Mol Syst Biol},
year = {2011},
volume = {7},
pages = {--},
month = may,
abstract = {Stochastic switching is considered as a cost-saving strategy for adaptation
to environmental challenges. We show here that stochastic switching
of a monostable circuit can mediate the adaptation of the engineered
OSU12-hisC Escherichia coli strain to histidine starvation. In this
strain, the hisC gene was deleted from the His operon and placed
under the control of a monostable foreign promoter. In response to
histidine depletion, the OSU12-hisC population shifted to a higher
HisC expression level, which is beneficial under starving conditions
but is not favoured by the monostable circuit. The population shift
was accompanied by growth recovery and was reversible upon histidine
addition. A weak directionality in stochastic switching of hisC was
observed in growing microcolonies under histidine-free conditions.
Directionality and fate decision were in part dependent on the initial
cellular status. Finally, microarray analysis indicated that OSU12-hisC
reorganized its transcriptome to reach the appropriate physiological
state upon starvation. These findings suggest that bacteria do not
necessarily need to evolve signalling mechanisms to control gene
expression appropriately, even for essential genes.},
comment = {10.1038/msb.2011.24},
publisher = {EMBO and Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/msb.2011.24}
}
@ARTICLE{Tsuzuki2011,
author = {Tsuzuki, Minoru and Moskvin, Oleg V. and Kuribayashi, Masayuki and
Sato, Kiichi and Retamal, Susana and Abo, Mitsuru and Zeilstra-Ryalls,
Jill and Gomelsky, Mark},
title = {Salt Stress-Induced Changes in the Transcriptome, Compatible Solutes,
and Membrane Lipids in the Facultatively Phototrophic Bacterium Rhodobacter
sphaeroides},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {7551-7559},
number = {21},
abstract = {Responses to NaCl stress were investigated in phototrophically grown
Alphaproteobacterium Rhodobacter sphaeroides by transcriptome profiling,
mutational analysis, and measurements of compatible solutes and membrane
phospholipids. After exposure to salt stress, genes encoding two
putative glycine betaine uptake systems, proVWX and betS, were highly
upregulated. Mutational analysis revealed that BetS, not ProVWX,
was the primary transporter of this compatible solute. Upon the addition
of salt, exogenous glycine betaine was taken up rapidly, and maximal
intracellular levels were reached within minutes. In contrast, synthesis
of another important compatible solute in R. sphaeroides, trehalose,
increased slowly following salt stress, reaching maximal levels only
after several hours. This accumulation pattern was consistent with
the more gradual increase in salt-induced transcription of the trehalose
biosynthesis operon otsBA. Several genes encoding putative transcription
factors were highly induced by salt stress. Multiple copies of one
of these factors, crpO (RSP1275), whose product is a member of the
cyclic AMP receptor protein/fumarate and nitrate reduction regulator
(CRP/FNR) family, improved NaCl tolerance. When crpO was provided
in multicopy, expression of genes for synthesis or transport of compatible
solutes was unaltered, but the membrane phospholipid composition
became biased toward that found in salt-stressed cells. Collectively,
this study characterized transcriptional responses to salt stress,
correlated changes in transcription with compatible solute accumulation
rates, identified the main glycine betaine transporter and trehalose
synthase, characterized salt-induced changes in phospholipid composition,
and uncovered a transcription factor associated with changes in phospholipids.
These findings set the stage for deciphering the salt stress-responsive
regulatory network in R. sphaeroides.},
doi = {10.1128/AEM.05463-11},
eprint = {http://aem.asm.org/cgi/reprint/77/21/7551.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/21/7551}
}
@ARTICLE{Tsvetkova2010,
author = {Tsvetkova, Krassimira and Marvaud, Jean-Christophe and Lambert, Thierry},
title = {Analysis of the Mobilization Functions of the Vancomycin Resistance
Transposon Tn1549, a Member of a New Family of Conjugative Elements},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {702--713},
number = {3},
month = feb,
abstract = {Conjugative transfer from Clostridium symbiosum to enterococci of
Tn1549, which confers VanB-type vancomycin resistance, has been reported.
This indicates the presence of a transfer origin (oriT) in the element.
Transcription analysis of Tn1549 indicated that orf29, orf28, orfz,
and orf27 were cotranscribed. A pACYC184 derivative containing 250
bp intergenic to orf29-orf30 of Tn1549 was mobilized in Escherichia
coli recA::RP4::{Delta}nic provided that orf28 and orf29 were delivered
simultaneously. These open reading frame (ORF) genes were able to
promote mobilization in trans, but a cis-acting preference was observed.
On the basis of a mobilization assay, a minimal 28-bp oriT was delimited,
although the frequency of transfer was significantly reduced compared
to that of a 130-bp oriT fragment. The minimal oriT contained an
inverted repeat and a core, which was homologous to the cleavage
sequence found in certain Gram-positive rolling-circle replicating
(RCR) plasmids. While Orf29 was a mobilization accessory component
similar to MobC proteins, Orf28 was identified as a relaxase belonging
to a new phyletic cluster of the MOBp superfamily. The nick site
was identified within oriT by an oligonucleotide cleavage assay.
Closely related oriTs linked to mobilization genes were detected
in data banks; they were found in various integrative and conjugative
elements (ICEs) originating mainly from anaerobes. These results
support the notion that Tn1549 is a member of a MOBp clade. Interestingly,
the Tn1549-derived constructs were mobilized by RP4 in E. coli, suggesting
that a relaxosome resulting from DNA cleavage by Orf28 interacted
with the coupling protein TraG. This demonstrates the capacity of
Tn1549 to be mobilized by a heterologous transfer system.},
url = {http://jb.asm.org/cgi/content/abstract/192/3/702}
}
@BOOK{Tu2005,
title = {Drosophila Glutathione S[hyphen (true graphic)]Transferases},
publisher = {Academic Press},
year = {2005},
editor = {Helmut Sies and Packer, Lester},
author = {Tu, Chen[hyphen (true graphic)]Pei D. and Akgül, Bünyamin},
volume = {Volume 401},
pages = {204--226},
abstract = {The Drosophila glutathione S[hyphen (true graphic)]transferases (GSTs;
EC2.5.1.18) comprise a host of cytosolic proteins that are encoded
by a gene superfamily and a homolog of the human microsomal GST.
Biochemical studies of certain recombinant GSTs have linked their
enzymatic functions to important substrates such as the pesticide
DDT and 4[hyphen (true graphic)]hydroxynonenal, a reactive lipid
metabolite. Moreover, a correspondence has been observed between
resistance to insecticide substrates--such as DDT--and elevated enzyme
levels in resistant strains. Such significant, recurring connections
suggest that these gst genes may feature in a model for the development
of insecticide resistance. We have amassed substantial biochemical
support for relating the overexpression of a particular gst gene
to insecticide resistance but are still short of solid genetic evidence
to affirm a causal relationship. With the Drosophila system, we have
at our disposal genetic and molecular techniques such as p[hyphen
(true graphic)]element mutagenesis and excision, siRNA technology,
and versatile transgenic techniques. We can use these methods to
effect loss[hyphen (true graphic)]of[hyphen (true graphic)]function
and gain[hyphen (true graphic)]of[hyphen (true graphic)]function
conditions and, in these rendered contexts, study other potentially
important functions of the gst gene superfamily. An immediate problem
that comes to mind is the possible causal relationship between GST
substrate specificity and chemical resistance phenotype(s). In this
chapter, we present an analysis of selected strategies and laboratory
methods that may be useful in pursuing a variety of interesting problems.
We will cover three kinds of approaches--biochemistry, genetics,
and genomics--as important instruments in a toolkit for studies of
the Drosophila gst superfamily. We make the case that these approaches
(biochemistry, genetics, and genomics) have helped us gain important
insights and can continue to help the community gain a more complete
understanding of the biological functions of GSTs. Such knowledge
may be key in addressing questions about the detoxification of pesticides
and how oxidative stresses affect life span. We hope that these techniques
will prove fruitful in studying a host of other physiologic functions
as well.},
booktitle = {Gluthione Transferases and Gamma-Glutamyl Transpeptidases},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/B7CV2-4J0R5GP-F/2/c1b6e99630dd63fb42b8199dbc55c9ed}
}
@ARTICLE{Tu2011a,
author = {Tu, Ran and Martinez, Ronny and Prodanovic, Radivoje and Klein, Mathias
and Schwaneberg, Ulrich},
title = {A Flow Cytometry-Based Screening System for Directed Evolution of
Proteases},
journal = {J Biomol Screen},
year = {2011},
volume = {16},
pages = {285--294},
number = {3},
month = mar,
abstract = {Proteases are industrially important enzymes but often have to be
improved for their catalytic efficiency and stabilities to suit applications.
Flow cytometry screening technology based on in vitro compartmentalization
in double emulsion had been developed and applied on directed evolution
of paraoxonase and {beta}-galactosidase. Further advancements of
flow cytometry-based screening technologies will enable an ultra-high
throughput of variants offering novel opportunities in directed enzyme
evolution under high mutational loads. For the industrially important
enzyme class of proteases, a first flow cytometry-based screening
system for directed protease evolution has been developed based on
an extracellular protease-deficient Bacillus subtilis strain (WB800N),
a model protease (subtilisin Carlsberg), and a water-in-oil-in-water
double-emulsion technology. B. subtilis WB800N cells are encapsulated
in double emulsion with a fluorogenic substrate (rhodamine 110-containing
peptide), allowing the screening of protease variants in femtoliter
compartments at high throughput. The protease screening technology
was validated by employing an epPCR mutant library with a high mutational
load and screened for increased resistance toward the inhibitor antipain
dihydrochloride. A variant (K127R, T237P, M239I, I269V, Y310F, I372V)
with an improved relative resistance was isolated from a small population
of active variants, validating the reported protease flow cytometry
screening technology for increased inhibitor resistance.},
comment = {10.1177/1087057110396361},
url = {http://jbx.sagepub.com/cgi/content/abstract/16/3/285}
}
@ARTICLE{Tu2011,
author = {Tu, Wen-Yo and Huang, Yu-Chen and Liu, Li-Fan and Chang, Li-Hsueh
and Tam, Ming F.},
title = {Rpl12p affects the transcription of the PHO pathway high-affinity
inorganic phosphate transporters and repressible phosphatases},
journal = {Yeast},
year = {2011},
volume = {28},
pages = {481--493},
number = {6},
abstract = {The ribosomal protein Rpl12p of Saccharomyces cerevisiae is encoded
by duplicated genes, RPL12A and RPL12B. The gene products possess
an identical amino acid sequence. Yeast strain 6EA1, which lacks
both genes, is viable but exhibits a very slow-growth phenotype.
In this study, 6EA1 cells were transformed with plasmids carrying
either RPL12A or RPL12B, and the transcriptional profiles of wild-type
W303, 6EA1 and the transformed cells grown in synthetic complete
medium were examined by microarray analysis. Transcription of PHO84,
a gene encoding a high-affinity phosphate transporter, was drastically
suppressed in 6EA1. PHO84 expression is induced under phosphate-limiting
conditions. Therefore, cells were grown in low-phosphate medium and
transcripts encoding the PHO pathway proteins were quantified by
qRT–PCR. The high-affinity phosphate transporters and repressible
phosphatases were suppressed, while PHO4, a PHO pathway transcription
activator, was upregulated in 6EA1. Accordingly, phosphate transport
and acidic phosphatase activities were significantly decreased in
6EA1. Addition of RPL12A or RPL12B to 6EA1 largely lessens these
effects. We postulate that RPL12 has an extra-ribosomal function
in modulating the transcription of genes that need Pho4p activation.
Copyright © 2011 John Wiley & Sons, Ltd.},
doi = {10.1002/yea.1852},
issn = {1097-0061},
keywords = {RPL12 deletion, transcriptional profiling, phosphate transport, phosphatase
activity},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/yea.1852}
}
@ARTICLE{Tudoran2011,
author = {Tudoran, Oana and Soritau, Olga and Balacescu, Ovidiu and Balacescu,
Loredana and Braicu, Cornelia and Rus, Meda and Gherman, Claudia
and Virag, Piroska and Irimie, Florin and Neagoe, Ioana Berindan},
title = {Early transcriptional pattern of angiogenesis induced by EGCG treatment
in cervical tumor cells},
journal = {Journal of Cellular and Molecular Medicine},
year = {2011},
pages = {no--no},
abstract = {Abstract The major green tea polyphenol (-)-epigallocatechin- 3-gallate
(EGCG) has been shown to exhibit antitumor activities in several
tumor models. One of the possible mechanisms by which EGCG can inhibit
cancer progression is through the modulation of angiogenesis signaling
cascade. The tumor cells ability to tightly adhere to endothelium
is a very important process in the metastatic process, because once
disseminated into the bloodstream the tumor cells must re-establish
adhesive connections to endothelium in order to extravasate into
the target tissues. In this study we investigated the antiangiogenic
effects of EGCG treatment (10 μM) on human cervical tumor cells
(HeLa) by evaluating the changes in the expression pattern of 84
genes known to be involved in the angiogenesis process. Transcriptional
analysis revealed 11 genes to be differentially expressed and was
further validated by measuring the induced biological effects. Our
results show that EGCG treatment leads to the downregulation of genes
involved in the stimulation of proliferation, adhesion and motility
as well as invasion processes, but also to the upregulation of several
genes known to have antagonist effects. We observed reduced proliferation
rates, adhesion and spreading ability as well as invasiveness of
HeLa tumor cells upon treatment which suggest that EGCG might be
an important antiangiogenic therapeutic approach in cervical cancers.},
doi = {10.1111/j.1582-4934.2011.01346.x},
issn = {1582-4934},
keywords = {EGCG, gene expression, angiogenesis, HeLa cells},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2011.01346.x}
}
@ARTICLE{Tuli2003,
author = {Tuli, Richard and Tuli, Suraj and Nandi, Sumon and Huang, Xiaoxue
and Manner, Paul A. and Hozack, William J. and Danielson, Keith G.
and Hall, David J. and Tuan, Rocky S.},
title = {Transforming Growth Factor-{beta}-mediated Chondrogenesis of Human
Mesenchymal Progenitor Cells Involves N-cadherin and Mitogen-activated
Protein Kinase and Wnt Signaling Cross-talk},
journal = {J. Biol. Chem.},
year = {2003},
volume = {278},
pages = {41227--41236},
number = {42},
month = oct,
abstract = {The multilineage differentiation potential of adult tissue-derived
mesenchymal progenitor cells (MPCs), such as those from bone marrow
and trabecular bone, makes them a useful model to investigate mechanisms
regulating tissue development and regeneration, such as cartilage.
Treatment with transforming growth factor-{beta} (TGF-{beta}) superfamily
members is a key requirement for the in vitro chondrogenic differentiation
of MPCs. Intracellular signaling cascades, particularly those involving
the mitogen-activated protein (MAP) kinases, p38, ERK-1, and JNK,
have been shown to be activated by TGF-{beta}s in promoting cartilage-specific
gene expression. MPC chondrogenesis in vitro also requires high cell
seeding density, reminiscent of the cellular condensation requirements
for embryonic mesenchymal chondrogenesis, suggesting common chondro-regulatory
mechanisms. Prompted by recent findings of the crucial role of the
cell adhesion protein, N-cadherin, and Wnt signaling in condensation
and chondrogenesis, we have examined here their involvement, as well
as MAP kinase signaling, in TGF-{beta}1-induced chondrogenesis of
trabecular bone-derived MPCs. Our results showed that TGF-{beta}1
treatment initiates and maintains chondrogenesis of MPCs through
the differential chondro-stimulatory activities of p38, ERK-1, and
to a lesser extent, JNK. This regulation of MPC chondrogenic differentiation
by the MAP kinases involves the modulation of N-cadherin expression
levels, thereby likely controlling condensation-like cell-cell interaction
and progression to chondrogenic differentiation, by the sequential
up-regulation and progressive down-regulation of N-cadherin. TGF-{beta}1-mediated
MAP kinase activation also controls WNT-7A gene expression and Wnt-mediated
signaling through the intracellular {beta}-catenin-TCF pathway, which
likely regulates N-cadherin expression and subsequent N-cadherin-mediated
cell-adhesion complexes during the early steps of MPC chondrogenesis.},
url = {http://www.jbc.org/cgi/content/abstract/278/42/41227}
}
@ARTICLE{Tully2006,
author = {Tully, Douglas B. and Bao, Wenjun and Goetz, Amber K. and Blystone,
Chad R. and Ren, Hongzu and Schmid, Judith E. and Strader, Lillian
F. and Wood, Carmen R. and Best, Deborah S. and Narotsky, Michael
G. and Wolf, Douglas C. and Rockett, John C. and Dix, David J.},
title = {Gene expression profiling in liver and testis of rats to characterize
the toxicity of triazole fungicides},
journal = {Toxicology and Applied Pharmacology},
year = {2006},
volume = {215},
pages = {260--273},
number = {3},
month = sep,
abstract = {Four triazole fungicides were studied using toxicogenomic techniques
to identify potential mechanisms of action. Adult male Sprague-Dawley
rats were dosed for 14 days by gavage with fluconazole, myclobutanil,
propiconazole, or triadimefon. Following exposure, serum was collected
for hormone measurements, and liver and testes were collected for
histology, enzyme biochemistry, or gene expression profiling. Body
and testis weights were unaffected, but liver weights were significantly
increased by all four triazoles, and hepatocytes exhibited centrilobular
hypertrophy. Myclobutanil exposure increased serum testosterone and
decreased sperm motility, but no treatment-related testis histopathology
was observed. We hypothesized that gene expression profiles would
identify potential mechanisms of toxicity and used DNA microarrays
and quantitative real-time PCR (qPCR) to generate profiles. Triazole
fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51
enzyme but can also modulate the expression and function of mammalian
CYP genes and enzymes. Triazoles affected the expression of numerous
CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a
isoforms as well as other xenobiotic metabolizing enzyme (XME) and
transporter genes. For some genes, such as Ces2 and Udpgtr2, all
four triazoles had similar effects on expression, suggesting possible
common mechanisms of action. Many of these CYP, XME and transporter
genes are regulated by xeno-sensing nuclear receptors, and hierarchical
clustering of CAR/PXR-regulated genes demonstrated the similarities
of toxicogenomic responses in liver between all four triazoles and
in testis between myclobutanil and triadimefon. Triazoles also affected
expression of multiple genes involved in steroid hormone metabolism
in the two tissues. Thus, gene expression profiles helped identify
possible toxicological mechanisms of the triazole fungicides.},
issn = {0041-008X},
keywords = {Fluconazole, Myclobutanil, Propiconazole, Triadimefon, Cytochrome
P450, Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/B6WXH-4JTR8WM-1/2/0c8db1f3c45dacf3bdd5eac15a409880}
}
@BOOK{Tumbar2006,
title = {Epithelial Skin Stem Cells},
publisher = {Academic Press},
year = {2006},
editor = {Klimanskaya, Irina and Lanza, Robert},
author = {Tumbar, Tudorita},
volume = {Volume 419},
pages = {73--99},
abstract = {Major progress in understanding epithelial skin stem cells has been
accomplished. This has been possible by developing new methods for
labeling, tracking, isolating, and characterizing enriched populations
of stem cells. This chapter summarizes in vivo and in vitro assays
that are currently employed to analyze skin epithelial stem cells.
Despite progress, the definition of a stem cell is currently a functional
one. Unambiguous identification of a stem cell in intact tissue is
still not possible. These limitations hamper molecular studies aimed
at unraveling the cellular mechanisms operating in the stem cell
compartment. This chapter emphasizes current methods for analyzing
hair follicle stem cells, as opposed to other epithelial compartments,
because the hair follicle has been most intensively studied up to
date.},
booktitle = {Adult Stem Cells},
issn = {0076-6879},
url = {http://www.sciencedirect.com/science/article/B7CV2-4MFV3H4-4/2/b843fb438dd3f86dec19dac3c6916998}
}
@ARTICLE{Tun2008,
author = {Tun, Han W. and Personett, David and Baskerville, Karen A. and Menke,
David M. and Jaeckle, Kurt A. and Kreinest, Pamela and Edenfield,
Brandy and Zubair, Abba C. and O'Neill, Brian P. and Lai, Weil R.
and Park, Peter J. and McKinney, Michael},
title = {Pathway analysis of primary central nervous system lymphoma},
journal = {Blood},
year = {2008},
volume = {111},
pages = {3200--3210},
number = {6},
month = mar,
abstract = {Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse
large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide
gene expression comparison between PCNSL and non-CNS DLBCL was performed,
the latter consisting of both nodal and extranodal DLBCL (nDLBCL
and enDLBCL), to identify a "CNS signature." Pathway analysis with
the program SigPathway revealed that PCNSL is characterized notably
by significant differential expression of multiple extracellular
matrix (ECM) and adhesion-related pathways. The most significantly
up-regulated gene is the ECM-related osteopontin (SPP1). Expression
at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells
was demonstrated by immunohistochemistry. The alterations in gene
expression can be interpreted within several biologic contexts with
implications for PCNSL, including CNS tropism (ECM and adhesion-related
pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated
B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1),
aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive
metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature
discovered in our study may represent a true "CNS signature" because
we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic
scale and performed an in-depth bioinformatic analysis.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/6/3200}
}
@ARTICLE{Tunbridge2007,
author = {Tunbridge, Elizabeth M. and Lane, Tracy A. and Harrison, Paul J.},
title = {Expression of multiple catechol-o-methyltransferase (COMT) mRNA variants
in human brain},
journal = {Am. J. Med. Genet.},
year = {2007},
volume = {144B},
pages = {834--839},
number = {6},
abstract = {Abstract 10.1002/ajmg.b.30539.abs Catechol-o-methyltransferase (COMT)
is important for modulating dopamine levels, prefrontal cortex (PFC)
function, and several psychiatric phenotypes. A single COMT mRNA
has been described in human brain, which gives rise to membrane-bound
(MB)- and soluble (S)-COMT proteins. In addition, we have recently
described a novel COMT protein isoform in the human PFC, suggesting
that there are more COMT gene products expressed than are currently
appreciated. Therefore, we have investigated whether variant COMT
mRNAs are present in human brain. We used reverse transcription-PCR
(RT-PCR) to screen systematically for variant COMT mRNAs in human
frontal cortex. Intron-spanning primers were used for exon-to-exon
PCR reactions; additionally, specific primers were designed to sequences
in the NCBI Aceview database. The identity of amplicons was confirmed
by sequencing, and their regional distributions and 3′ untranslated
regions (UTRs) were characterised using RT-PCR. We detected 7 COMT
variant mRNAs, resulting from both insertions and deletions within
the known COMT brain transcript. Several of the variants alter the
predicted coding sequence. Three of these variants correspond to
sequences within the Aceview database and could be reliably amplified,
while the remaining four do not correspond to any expressed sequence
tags and were amplified only once. The regional distributions of
these transcripts are described. The results demonstrate multiple
COMT mRNAs in human brain, revealing an additional complexity to
the biology of COMT. The alternate gene products may be of significant
functional importance, and differentially impacted by polymorphisms
within the COMT gene. © 2007 Wiley-Liss, Inc.},
issn = {1552-485X},
keywords = {schizophrenia, prefrontal cortex, dopamine, mRNA splicing},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.30539}
}
@ARTICLE{Tung2011,
author = {Tung, Edmund Kwok-Kwan and Mak, Carmen Ka-Man and Fatima, Sarwat
and Lo, Regina Cheuk-Lam and Zhao, Heng and Zhang, Chunsheng and
Dai, Hongyue and Poon, Ronnie Tung-Ping and Yuen, Man-Fung and Lai,
Ching-Lung and Li, Jin-jun and Luk, John Moon-Ching and Ng, Irene
Oi-Lin},
title = {Clinicopathological and prognostic significance of serum and tissue
Dickkopf-1 levels in human hepatocellular carcinoma},
journal = {Liver International},
year = {2011},
volume = {31},
pages = {1494--1504},
number = {10},
abstract = {Background:Although Dickkopf-1 (DKK1) is known to be a negative regulator
of the Wnt/β-catenin pathway, it has been recently found to be upregulated
in cancers.Aims:We investigated the clinical and prognostic significance
of both serum and transcript DKK1 and its functional roles in human
hepatocellular carcinoma (HCC).Methods:We evaluated the expression
level of DKK1 in both tissue and serum samples from patients with
HCC using GeneChip microarray and real-time-quantitative PCR and
sandwich ELISA system respectively. The clinicopathological and prognostic
significance of serum and tissue DKK1 levels was examined. Functional
characterization of DKK1 with regard to cell migration, invasion
and tumour growth was performed.Results:Both DKK1 transcript and
serum protein were upregulated in a stepwise manner in human HCCs.
Its transcript levels were associated with more aggressive tumour
behaviour, in terms of venous invasion (PÂ =Â 0.003), advanced tumour
stage (PÂ =Â 0.003). DKK1 transcript correlated with shorter overall
(PÂ =Â 0.006) and disease-free survival (PÂ =Â 0.012), and higher
serum DKK1 levels correlated with shorter disease-free survival (PÂ =Â 0.046).
Knockdown of DKK1 significantly reduced both migratory and invasive
abilities of HCC cells, whereas overexpression of DKK1 enhanced the
tumour formation efficiency and tumour growth in vivo.Conclusions:Serum
and tissue DKK1 levels increased in a stepwise manner in multistep
hepatocarcinogenesis and had prognostic significance. DKK1 plays
a functional role in cell migration, invasion and tumour growth.},
doi = {10.1111/j.1478-3231.2011.02597.x},
issn = {1478-3231},
keywords = {biomarker, DKK1, HCC, prognosis, Wnt},
url = {http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x}
}
@ARTICLE{Tung2008,
author = {Tung, Yi-Chun Loraine and Ma, Marcella and Piper, Sarah and Coll,
Anthony and O'Rahilly, Stephen and Yeo, Giles S. H.},
title = {Novel Leptin-Regulated Genes Revealed by Transcriptional Profiling
of the Hypothalamic Paraventricular Nucleus},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {12419--12426},
number = {47},
month = nov,
abstract = {Leptin plays a major role in coordinating the integrated response
of the CNS to changes in nutritional state. Neurons within the paraventricular
nucleus (PVN) of the hypothalamus express leptin receptors and receive
dense innervation from leptin receptor-expressing neurons in the
arcuate nucleus. To obtain new insights into the effects of circulating
leptin on PVN function, we compared global transcriptional profiles
of laser-captured PVN from ad libitum fed mice versus 48 h fasted
mice receiving either sham or leptin treatment intraperitoneally.
Five hundred twenty-seven PVN-expressed genes were altered by fasting
in a manner that was at least partially reversible by leptin. Consistent
with previous reports, thyrotrophin releasing hormone mRNA levels
were decreased by fasting but restored to fed levels with leptin
treatment. mRNA levels of oxytocin, vasopressin, and somatostatin
were also reduced by fasting and restored by leptin. Given the known
effects of leptin on synaptic remodeling, it is notable that, among
the top 15 genes that were positively regulated by leptin, five have
been implicated in synaptic function and/or plasticity (basigin,
apolipoprotein E, Gap43, GABAA receptor-associated protein, and synuclein-{gamma}).
Pathway analysis identified oxidative phosphorylation, in particular,
genes encoding complex 1 proteins that play a role in ubiquinone
biosynthesis, to be the predominant gene set that was significantly
regulated in a leptin-dependent manner. Thus, in addition to its
effects on the expression of a broad range of neuropeptides, leptin
may also exert more general influences on synaptic function in, and
the bioenergetic state of, the PVN.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/47/12419}
}
@ARTICLE{Tunsjoe2011,
author = {Tunsjø, Hege Smith and Wiik-Nielsen, Christer R. and Grove, Søren
and Skjerve, Eystein and Sørum, Henning and L'Abée-Lund, Trine M.},
title = {Putative virulence genes in Moritella viscosa: Activity during in
vitro inoculation and in vivo infection},
journal = {Microbial Pathogenesis},
year = {2011},
volume = {50},
pages = {286--292},
number = {6},
month = jun,
abstract = {Moritella viscosa is considered to be the main aetiological agent
of winter ulcer disease, primarily affecting farmed salmonid fish
in cold marine waters. Transcription profiles of twelve M. viscosa
genes, potentially involved in the pathogenesis, were studied during
the course of an in vitro cell culture infection assay. Transcription
of the same genes was compared in vivo, in head kidney and ulcer
tissues of Atlantic salmon challenged with M. viscosa. During the
in vitro infection, three putative toxins: a putative repeats in
toxin gene (rtxA), a putative cytotoxic necrotizing factor (cnf)
and a putative hemolysin increased their transcription significantly
with time and coincident with cell rounding. Furthermore, the majority
of the genes were stimulated by presence of fish cells and showed
higher activity when adhered to fish cells compared to their planktonic
counterpart. In vivo gene transcription studies revealed an up-regulation
of a putative lateral flagellin in ulcer compared to head kidney
tissues in the same individual. A similar trend was seen for cnf
and a gene encoding a putative protease, indicating a role for these
factors in colonization and tissue damage.},
issn = {0882-4010},
keywords = {Moritella viscosa, Winter ulcer, Virulence, Colonization, Gene transcription,
In vivo},
url = {http://www.sciencedirect.com/science/article/pii/S0882401011000258}
}
@ARTICLE{Tupin2004,
author = {Tupin, Emmanuel and Nicoletti, Antonino and Elhage, Rima and Rudling,
Mats and Ljunggren, Hans-Gustaf and Hansson, Goran K. and Berne,
Gabrielle Paulsson},
title = {CD1d-dependent Activation of NKT Cells Aggravates Atherosclerosis},
journal = {J. Exp. Med.},
year = {2004},
volume = {199},
pages = {417--422},
number = {3},
month = feb,
abstract = {Adaptive and innate immunity have been implicated in the pathogenesis
of atherosclerosis. Given their abundance in the lesion, lipids might
be targets of the atherosclerosis-associated immune response. Natural
killer T (NKT) cells can recognize lipid antigens presented by CD1
molecules. We have explored the role of CD1d-restricted NKT cells
in atherosclerosis by using apolipoprotein E-deficient (apoE-/-)
mice, a hypercholesterolemic mouse model that develops atherosclerosis.
ApoE-/- mice crossed with CD1d-/- (CD1d-/-apoE-/-) mice exhibited
a 25% decrease in lesion size compared with apoE-/- mice. Administration
of {alpha}-galactosylceramide, a synthetic glycolipid that activates
NKT cells via CD1d, induced a 50% increase in lesion size in apoE-/-
mice, whereas it did not affect lesion size in apoE-/-CD1d-/- mice.
Treatment was accompanied by an early burst of cytokines (IFN{gamma},
MCP-1, TNF{alpha}, IL-2, IL-4, IL-5, and IL-6) followed by sustained
increases in IFN{gamma} and IL-4 transcripts in the spleen and aorta.
Early activation of both T and B cells was followed by recruitment
of T and NKT cells to the aorta and activation of inflammatory genes.
These results show that activation of CD1d-restricted NKT cells exacerbates
atherosclerosis.},
url = {http://jem.rupress.org/cgi/content/abstract/199/3/417}
}
@ARTICLE{Turetz2009,
author = {Turetz, Meredith L. and O’Connor, Timothy P. and Tilley, Ann E.
and Strulovici-Barel, Yael and Salit, Jacqueline and Dang, David
and Teater, Matthew and Mezey, Jason and Clark, Andrew G. and Crystal,
Ronald G.},
title = {Trachea Epithelium as a “Canary� for Cigarette Smoking-Induced
Biologic Phenotype of the Small Airway Epithelium},
journal = {Clinical and Translational Science},
year = {2009},
volume = {2},
pages = {260--272},
number = {4},
abstract = {Abstract The initial site of smoking-induced lung disease is the small
airway epithelium, which is difficult and time consuming to sample
by fiberoptic bronchoscopy. We developed a rapid, office-based procedure
to obtain trachea epithelium without conscious sedation from healthy
nonsmokers (n= 26) and healthy smokers (n= 19, 27 ± 15 pack-year).
Gene expression differences (fold change >1.5, p < 0.01, Benjamini–Hochberg
correction) were assessed with Affymetrix microarrays. A total of
1,057 probe sets were differentially expressed in healthy smokers
versus nonsmokers, representing >500 genes. Trachea gene expression
was compared to an independent group of small airway epithelial samples
(n= 23 healthy nonsmokers, n= 19 healthy smokers, 25 ± 12 pack-year).
The trachea epithelium is more sensitive to smoking, responding with
threefold more differentially expressed genes than small airway epithelium.
The trachea transcriptome paralleled the small airway epithelium,
with 156 of 167 (93%) genes that are significantly up- and downregulated
by smoking in the small airway epithelium showing similar direction
and magnitude of response to smoking in the trachea. Trachea epithelium
can be obtained without conscious sedation, representing a less invasive
surrogate “canary� for smoking-induced changes in the small airway
epithelium. This should prove useful in epidemiologic studies correlating
gene expression with clinical outcome in assessing smoking-induced
lung disease.},
issn = {1752-8062},
keywords = {epithelium, airway, gene expression},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1752-8062.2009.00129.x}
}
@ARTICLE{Turhan2009,
author = {Turhan, Aslihan and Lin, Miao and Lee, Grace S. and Miele, Lino F.
and Tsuda, Akira and Konerding, Moritz A. and Mentzer, Steven J.},
title = {Vascular Microarchitecture of Murine Colitis-Associated Lymphoid
Angiogenesis},
journal = {Anat Rec},
year = {2009},
volume = {292},
pages = {621--632},
number = {5},
abstract = {Abstract 10.1002/ar.20902.abs In permissive tissues, such as the gut
and synovium, chronic inflammation can result in the ectopic development
of anatomic structures that resemble lymph nodes. These inflammation-induced
structures, termed lymphoid neogenesis or tertiary lymphoid organs,
may reflect differential stromal responsiveness to the process of
lymphoid neogenesis. To investigate the structural reorganization
of the microcirculation involved in colonic lymphoid neogenesis,
we studied a murine model of dextran sodium sulfate (DSS)-induced
colitis. Standard 2-dimensional histology demonstrated both submucosal
and intramucosal lymphoid structures in DSS-induced colitis. A spatial
frequency analysis of serial histologic sections suggested that most
intramucosal lymphoid aggregates developed de novo. Intravital microscopy
of intravascular tracers confirmed that the developing intramucosal
aggregates were supplied by capillaries arising from the quasi-polygonal
mucosal plexus. Confocal optical sections and whole mount morphometry
demonstrated capillary networks (185 ± 46 μm diameter) involving
six to ten capillaries with a luminal diameter of 6.8 ± 1.1 μm.
Microdissection and angiogenesis PCR array analysis demonstrated
enhanced expression of multiple angiogenic genes including CCL2,
CXCL2, CXCL5, Il-1b, MMP9, and TNF within the mucosal plexus. Intravital
microscopy of tracer particle flow velocities demonstrated a marked
decrease in flow velocity from 808 ± 901 μm/sec within the feeding
mucosal plexus to 491 ± 155 μm/sec within the capillary structures.
We conclude that the development of ectopic lymphoid tissue requires
significant structural remodeling of the stromal microcirculation.
A feature of permissive tissues may be the capacity for lymphoid
angiogenesis. Anat Rec, 292:621–632, 2009. © 2009 Wiley-Liss,
Inc.},
issn = {1932-8494},
keywords = {microcirculation, lymphoid neogenesis, angiogenesis, colitis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ar.20902}
}
@ARTICLE{Turk2011,
author = {Turk, Kendra A. and Rees, Andrew P and Zehr, Jonathan P and Pereira,
Nicole and Swift, Paul and Shelley, Rachel and Lohan, Maeve and Woodward,
E Malcolm S and Gilbert, Jack},
title = {Nitrogen fixation and nitrogenase (nifH) expression in tropical waters
of the eastern North Atlantic},
journal = {ISME J},
year = {2011},
volume = {5},
pages = {1201-1212},
month = jan,
issn = {1751-7362},
publisher = {International Society for Microbial Ecology},
url = {http://dx.doi.org/10.1038/ismej.2010.205}
}
@ARTICLE{Turkkahraman2008,
author = {Turkkahraman, Doga and Bircan, Iffet and Tribble, Nicholas D. and
Akçurin, Sema and Ellard, Sian and Gloyn, Anna L.},
title = {Permanent Neonatal Diabetes Mellitus Caused by a Novel Homozygous
(T168A) Glucokinase (GCK) Mutation: Initial Response to Oral Sulphonylurea
Therapy},
journal = {The Journal of Pediatrics},
year = {2008},
volume = {153},
pages = {122--126},
number = {1},
month = jul,
abstract = {Objective To evaluate the clinical response to sulphonylurea treatment
in a child with a homozygous T168A GCK (glucokinase) mutation, causing
permanent neonatal diabetes mellitus (PNDM).Study design Oral glibenclamide
was given for 3 months. Pancreatic beta cell function was assessed
by a glucagon stimulation test. Mutant and wild-type (WT) GCK were
characterized.Results Sulphonylurea treatment resulted in a 12-fold
increase in basal and stimulated C-peptide levels. HbA1c levels were
reduced from 9.4% to 8.1% on a reduced insulin dose (0.85 to 0.60
U/kg/day). Mutant T168A-GST-GCK showed reduced kinetic activity (0.02
fold) compared to WT.Conclusions Sulphonylureas can close the adenosine
triphosphate (ATP)-sensitive potassium channel and elicit insulin
secretion, but the ATP generated from metabolism is insufficient
to fully restore insulin secretory capacity. Nonetheless, sulphonylurea
treatment should be tried in patients with GCK-PNDM, particularly
those with mutations resulting in less severe kinetic defects, in
whom improved glycemic control may be obtained with lower doses of
insulin.},
issn = {0022-3476},
url = {http://www.sciencedirect.com/science/article/B6WKR-4S0HC7S-2/2/4a2a764566d8e00df8de3780eadad5ea}
}
@ARTICLE{Turner2011,
author = {Turner, Daniel J. and Tuytten, Robin and Janssen, Kris P.F. and Lammertyn,
Jeroen and Wuyts, Jan and Pollet, Jeroen and Eyckerman, Sven and
Brown, Clive and Kas, Koen},
title = {Toward Clinical Proteomics on a Next-Generation Sequencing Platform},
journal = {Analytical Chemistry},
year = {2011},
volume = {83},
pages = {666-670},
number = {3},
doi = {10.1021/ac102666n},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac102666n},
url = {http://pubs.acs.org/doi/abs/10.1021/ac102666n}
}
@ARTICLE{Turner2007,
author = {Turner, Helen C. and Budak, Murat T. and Akinci, M. A. Murat and
Wolosin, J. Mario},
title = {Comparative Analysis of Human Conjunctival and Corneal Epithelial
Gene Expression with Oligonucleotide Microarrays},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {2050--2061},
number = {5},
month = may,
abstract = {PURPOSE. To determine global mRNA expression levels in corneal and
conjunctival epithelia and identify transcripts that exhibit preferential
tissue expression. METHODS. cDNA samples derived from human conjunctival
and corneal epithelia were hybridized in three independent experiments
to a commercial oligonucleotide array representing more than 22,000
transcripts. The resultant signal intensities and microarray software
transcript present/absent calls were used in conjunction with the
local pooled error (LPE) statistical method to identify transcripts
that are preferentially or exclusively expressed in one of the two
tissues at significant levels (expression >1% of the {beta}-actin
level). EASE (Expression Analysis Systematic Explorer software) was
used to identify biological systems comparatively overrepresented
in either epithelium. Immuno-, and cytohistochemistry was performed
to validate or expand on selected results of interest. RESULTS. The
analysis identified 332 preferential and 93 exclusive significant
corneal epithelial transcripts. The corresponding numbers of conjunctival
epithelium transcripts were 592 and 211, respectively. The overrepresented
biological processes in the cornea were related to cell adhesion
and oxiredox equilibria and cytoprotection activities. In the conjunctiva,
the biological processes that were most prominent were related to
innate immunity and melanogenesis. Immunohistochemistry for antigen-presenting
cells and melanocytes was consistent with these gene signatures.
The transcript comparison identified a substantial number of genes
that have either not been identified previously or are not known
to be highly expressed in these two epithelia, including testican-1,
ECM1, formin, CRTAC1, and NQO1 in the cornea and, in the conjunctiva,
sPLA2-IIA, lipocalin 2, IGFBP3, multiple MCH class II proteins, and
the Na-Pi cotransporter type IIb. CONCLUSIONS. Comparative gene expression
profiling leads to the identification of many biological processes
and previously unknown genes that are potentially active in the function
of corneal and conjunctival epithelia.},
url = {http://www.iovs.org/cgi/content/abstract/48/5/2050}
}
@ARTICLE{Turner2011a,
author = {Turner, L and Heath, JD and Kurn, N},
title = {Gene expression profiling of RNA extracted from FFPE tissues: NuGEN
technologies' whole-transcriptome amplification system.},
journal = {Methods in Molecular Biology},
year = {2011},
volume = {724},
pages = {269-280},
month = jan,
url = {http://www.ncbi.nlm.nih.gov/pubmed/21370019}
}
@ARTICLE{Turner2005,
author = {Turner, Matthew J. and Sowders, Dawn P. and DeLay, Monica L. and
Mohapatra, Rajashree and Bai, Shuzhen and Smith, Judith A. and Brandewie,
Jaclyn R. and Taurog, Joel D. and Colbert, Robert A.},
title = {HLA-B27 Misfolding in Transgenic Rats Is Associated with Activation
of the Unfolded Protein Response},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {2438--2448},
number = {4},
month = aug,
abstract = {The mechanism by which the MHC class I allele, HLA-B27, contributes
to spondyloarthritis pathogenesis is unknown. In contrast to other
alleles that have been examined, HLA-B27 has a tendency to form high
m.w. disulfide-linked H chain complexes in the endoplasmic reticulum
(ER), bind the ER chaperone BiP/Grp78, and undergo ER-associated
degradation. These aberrant characteristics have provided biochemical
evidence that HLA-B27 is prone to misfold. Recently, similar biochemical
characteristics of HLA-B27 were reported in cells from HLA-B27/human
{beta}2-microglobulin transgenic (HLA-B27 transgenic) rats, an animal
model of spondyloarthritis, and correlated with disease susceptibility.
In this study, we demonstrate that the unfolded protein response
(UPR) is activated in macrophages derived from the bone marrow of
HLA-B27 transgenic rats with inflammatory disease. Microarray analysis
of these cells also reveals an IFN response signature. In contrast,
macrophages derived from premorbid rats do not exhibit a strong UPR
or evidence of IFN exposure. Activation of macrophages from premorbid
HLA-B27 transgenic rats with IFN-{gamma} increases HLA-B27 expression
and leads to UPR induction, while no UPR is seen in cells from nondisease-prone
HLA-B7 transgenic or wild-type (nontransgenic) animals. This is the
first demonstration, to our knowledge, that HLA-B27 misfolding is
associated with ER stress that results in activation of the UPR.
These observations link HLA-B27 expression with biological effects
that are independent of immunological recognition, but nevertheless
may play an important role in the pathogenesis of inflammatory diseases
associated with this MHC class I allele.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/4/2438}
}
@ARTICLE{Turner2007a,
author = {Turner, Terry T. and Johnston, Daniel S. and Finger, Joshua N. and
Jelinsky, Scott A.},
title = {Differential Gene Expression among the Proximal Segments of the Rat
Epididymis Is Lost after Efferent Duct Ligation},
journal = {Biol Reprod},
year = {2007},
volume = {77},
pages = {165--171},
number = {1},
month = jul,
abstract = {The epididymis has traditionally been divided into the caput, corpus,
and cauda regions, which are further organized into intraregional
segments. In the rat and mouse, these segments have high degrees
of transcriptional differentiation, and what has traditionally been
called the initial segment of the rat epididymis actually consists
of three transcriptionally different intraregional segments. These
segments are regulated by endocrine, lumicrine, and paracrine factors,
whose relative importance remains a topic of investigation. In the
present study, 15-day unilateral efferent duct ligation (EDL) was
used to deprive ipsilateral rat epididymides of lumicrine regulation.
Segments 1-4 of EDL epididymides and contralateral, sham-operated
tissues were collected individually. Microarray analysis of gene
expression was used to determine the effect of lumicrine factor deprivation
on the transcriptome-wide gene expression of each segment studied.
More than 11 000 genes were detected as being expressed in each of
the four segments examined. More than 2000 genes responded significantly
to EDL in segment 1, although this number of genes declined in each
succeeding segment. Segments 1 and 2 of control tissues were the
most different transcriptionally and the most affected by EDL. In
the absence of lumicrine factors, the four segments regressed to
a transcriptionally undifferentiated state, which was consistent
with the less-differentiated histology seen after EDL. Interestingly,
for an individual gene, lumicrine factor deprivation could stimulate
expression in some segments and suppress expression in other segments.
These results reveal a higher complexity to the regulation of rat
epididymal segments than heretofore appreciated.},
url = {http://www.biolreprod.org/cgi/content/abstract/77/1/165}
}
@ARTICLE{Turner2007b,
author = {Turner, Terry T. and Johnston, Daniel S. and Jelinsky, Scott A. and
Tomsig, Jose L. and Finger, Joshua N.},
title = {Segment boundaries of the adult rat epididymis limit interstitial
signaling by potential paracrine factors and segments lose differential
gene expression after efferent duct ligation},
journal = {Asian Journal of Andrology},
year = {2007},
volume = {9},
pages = {565--573},
number = {4},
abstract = {Abstract The epididymis is divided into caput, corpus and cauda regions,
organized into intraregional segments separated by connective tissue
septa (CTS). In the adult rat and mouse these segments are highly
differentiated. Regulation of these segments is by endocrine, lumicrine
and paracrine factors, the relative importance of which remains under
investigation. Here, the ability of the CTS to limit signaling in
the interstitial compartment is reviewed as is the effect of 15 days
of unilateral efferent duct ligation (EDL) on ipsilateral segmental
transcriptional profiles. Inter-segmental microperifusions of epidermal
growth factor (EGF), vascular endothelial growth factor (VEGFA) and
fibroblast growth factor 2 (FGF2) increased phosphorylation of mitogen
activated protein kinase (MAPK) in segments 1 and 2 of the rat epididymis
and the effects of all factors were limited by the CTS separating
the segments. Microarray analysis of segmental gene expression determined
the effect of 15 days of unilateral EDL on the transcriptome-wide
gene expression of rat segments 1-4. Over 11 000 genes were expressed
in each of the four segments and over 2 000 transcripts in segment
1 responded to deprivation of testicular lumicrine factors. Segments
1 and 2 of control tissues were the most transcriptionally different
and EDL had its greatest effects there. In the absence of lumicrine
factors, all four segments regressed to a transcriptionally undifferentiated
state, consistent with the less differentiated histology. Deprivation
of lumicrine factors could stimulate an individual gene's expression
in some segments yet suppress it in others. Such results reveal a
higher complexity of the regulation of rat epididymal segments than
that is generally appreciated.},
issn = {1745-7262},
keywords = {efferent duct ligation, dedifferentiation, proximal epididymis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1745-7262.2007.00302.x}
}
@ARTICLE{Turnock-Jones2009,
author = {Turnock-Jones, Julia J. and Jennings, Carol A. and Robbins, Melanie
J. and Cluderay, Jane E. and Cilia, Jackie and Reid, Juliet L. and
Taylor, Adam and Jones, Declan N.C. and Emson, Piers C. and Southam,
Eric},
title = {Increased expression of the NR2A NMDA receptor subunit in the prefrontal
cortex of rats reared in isolation},
journal = {Synapse},
year = {2009},
volume = {63},
pages = {836--846},
number = {10},
abstract = {Abstract 10.1002/syn.20665.abs A hypofunction of the N-methyl-D-aspartate
(NMDA) receptor has been implicated in the pathophysiology of schizophrenia.
Compelling evidence of altered NMDA receptor subunit expression in
the schizophrenic brain has not, however, so far emerged. Rats reared
in isolation exhibit several characteristics, including disturbed
sensory gating, which resemble those seen in schizophrenia. To explore
the possibility that NMDA receptor dysfunction may contribute to
the behavioral and neurochemical consequences of rearing rats in
isolation, we compared NMDA receptor subunit expression in brains
of rats which were housed in isolation and which displayed a deficit
in prepulse inhibition of the acoustic startle response with that
of socially housed controls. An initial microarray analysis revealed
a 1.26-fold increase in NR2A transcript in the prefrontal cortex,
but not in the nucleus accumbens, of rats reared in isolation compared
with those housed socially. In contrast, NR1, NR2B, NR2C, NR2D, NR3A,
and NR3B subunit expression was unchanged in either brain area. In
a second cohort of animals, in situ hybridization revealed increased
NR2A mRNA expression in the medial prefrontal cortex, an observation
that was substantiated by increased [3H]CGP39653 binding suggesting
that NR2A receptor subunit protein expression was also elevated in
the medial prefrontal cortex of the same animals. No changes in expression
of NR1 or NR2B subunits were observed at both mRNA and protein level.
Altered NR2A subunit expression in the medial prefrontal cortex of
rats reared in isolation suggests that NMDA receptor dysfunction
may contribute to the underlying pathophysiology of this preclinical
model of aspects of schizophrenia. Synapse 63:836–846, 2009. ©
2009 Wiley-Liss, Inc.},
issn = {1098-2396},
keywords = {animal model, prepulse inhibition, schizophrenia, isolate},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/syn.20665}
}
@ARTICLE{Tuschl2009,
author = {Tuschl, Gregor and Hrach, Jens and Walter, Yvonne and Hewitt, Philip
G. and Mueller, Stefan O.},
title = {Serum-free collagen sandwich cultures of adult rat hepatocytes maintain
liver-like properties long term: A valuable model for in vitro toxicity
and drug-drug interaction studies},
journal = {Chemico-Biological Interactions},
year = {2009},
volume = {181},
pages = {124--137},
number = {1},
month = sep,
abstract = {Cultures of primary hepatocytes from various species, including human,
are used in several applications during pre-clinical drug development.
Their use is however limited by cell survival and conservation of
liver-specific functions in vitro. The differentiation status of
hepatocytes in culture strongly depends on medium formulation and
the extracellular matrix environment. We incubated primary rat hepatocytes
for 10 days on collagen monolayer and in collagen sandwich cultures
with or without serum. Restoration of polygonal cell shape and formation
of functional bile canaliculi-like structures was stable only in
serum-free sandwich cultures. Variations in general cell viability,
as judged by the cellular ATP content, LDH release or apoptosis,
were less pronounced between alternative cultures. The intracellular
glutathione content was preserved close to in vivo levels especially
in serum-free sandwich cultures. Basal activities of cytochrome P450
enzymes (P450) varied strongly between cultures. There was a minor
effect on CYP1A but CYP2B activity was only detectable in the serum-free
sandwich culture after 3 days and beyond. CYP2C activity was slightly
elevated in both sandwich cultures, whereas CYP3A showed increased
levels in both serum-free cultures. Inducibility of these P450s was
fully maintained over time in serum-free collagen sandwich only.
Gene expression was largely constant over time in serum-free sandwich
cultures that was closest to liver. This liver-like property was
supported by protein profiling results. Taken together, the serum-free
collagen sandwich culture of primary rat hepatocytes maintained liver-like
features over 10 days and is therefore a suitable model for long-term
toxicity and drug-drug interaction studies.},
issn = {0009-2797},
keywords = {Primary hepatocytes, In vitro model, Sandwich culture, Cytochrome
P450 induction, Real-time PCR, Bile canaliculi},
url = {http://www.sciencedirect.com/science/article/B6T56-4WD7B7C-1/2/de5bc2036c55765a26be843149df1b19}
}
@ARTICLE{Tuschl2006,
author = {Tuschl, Gregor and Mueller, Stefan O.},
title = {Effects of cell culture conditions on primary rat hepatocytes--Cell
morphology and differential gene expression},
journal = {Toxicology},
year = {2006},
volume = {218},
pages = {205--215},
number = {2-3},
month = feb,
abstract = {We incubated primary rat hepatocytes on collagen monolayer as well
as in collagen sandwich cultures with serum-containing or serum-free
medium formulations. Morphological monitoring of hepatocytes revealed
that hepatocytes cultured on collagen monolayer adopted their polygonal
shape and started to create aggregates earlier than sandwich-cultured
cells. Bile canaliculi-like structures were observed in every cell
culture system but were more prominent in serum-free cultures. Hepatocytes
in collagen-sandwich configuration and serum-free medium were the
most viable after 72 h of culture, still displaying polygonal shape,
clear cytoplasm and stable canaliculi-like structures. Differential
gene expression patterns were determined for each cell culture condition
using quantitative TaqMan® Low Density Arrays (LDA). Gene expression
analysis revealed distinct profiles in monolayer versus sandwich
cultures and in particular in serum-free versus serum-containing
culture medium. The hepatocytes cultured in the collagen-sandwich
with serum-free medium showed the least variation in expression values
over time. Importantly, stress markers were not induced in the serum-free
sandwich culture, in contrast to the monolayer and the serum-containing
sandwich cultures. Additionally, expression of the investigated cytochrome
P450 genes was maintained in the serum-free monolayer and the sandwich
cultures. In conclusion, culturing primary rat hepatocytes in a sandwich
between two layers of gelled collagen and in a serum-free medium
formulation, appears to be most suitable for long-term in vitro hepatotoxicity
screening.},
issn = {0300-483X},
keywords = {Monolayer culture, Sandwich culture, Real-time PCR, TaqMan® Low Density
Array},
url = {http://www.sciencedirect.com/science/article/B6TCN-4HRDYB2-1/2/f3a0a6cfafdf48186e5be3d5b76b7f35}
}
@ARTICLE{Tuteja2009,
author = {Tuteja, Geetu and White, Peter and Schug, Jonathan and Kaestner,
Klaus H.},
title = {Extracting transcription factor targets from ChIP-Seq data},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {e113--},
number = {17},
month = sep,
abstract = {ChIP-Seq technology, which combines chromatin immunoprecipitation
(ChIP) with massively parallel sequencing, is rapidly replacing ChIP-on-chip
for the genome-wide identification of transcription factor binding
events. Identifying bound regions from the large number of sequence
tags produced by ChIP-Seq is a challenging task. Here, we present
GLITR (GLobal Identifier of Target Regions), which accurately identifies
enriched regions in target data by calculating a fold-change based
on random samples of control (input chromatin) data. GLITR uses a
classification method to identify regions in ChIP data that have
a peak height and fold-change which do not resemble regions in an
input sample. We compare GLITR to several recent methods and show
that GLITR has improved sensitivity for identifying bound regions
closely matching the consensus sequence of a given transcription
factor, and can detect bona fide transcription factor targets missed
by other programs. We also use GLITR to address the issue of sequencing
depth, and show that sequencing biological replicates identifies
far more binding regions than re-sequencing the same sample.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/17/e113}
}
@ARTICLE{Tvermoes2010,
author = {Tvermoes, Brooke E. and Boyd, Windy A. and Freedman, Jonathan H.},
title = {Molecular characterization of numr-1 and numr-2: genes that increase
both resistance to metal-induced stress and lifespan in Caenorhabditis
elegans},
journal = {J. Cell Sci.},
year = {2010},
volume = {123},
pages = {2124--2134},
number = {12},
month = jun,
abstract = {To define the mechanisms involved in the molecular response to the
carcinogenic metal cadmium, two novel metal-inducible genes from
C. elegans were characterized: numr-1 and numr-2 (nuclear localized
metal responsive). numr-1 and numr-2 sequences and cellular patterns
of expression are identical, indicating that these are functionally
equivalent genes. Constitutive transcription of numr-1 and numr-2
is developmentally regulated and occurs in the intestine, in head
and tail neurons, and vulva muscles. Exposure to metals induces numr-1
and numr-2 transcription in pharyngeal and intestinal cells. Other
environmental stressors do not affect transcription, indicating that
these are metal-specific, stress-responsive genes. NUMR-1 and NUMR-2
target to nuclei and colocalize with HSF-1, suggesting that they
may be components of nuclear stress granules. Nematodes overexpressing
NUMR-1 and NUMR-2 are resistant to stress and live longer than control
animals; likewise reducing expression increases sensitivity to metals
and decreases neuromuscular functions. Upstream regulatory regions
of both genes contain potential binding sites for DAF-16 and SKN-1,
which are components of the insulin-IGF-like signaling pathway. This
pathway regulates longevity and stress responses in C. elegans. NUMR-1
and NUMR-2 may function to promote resistance to environmental stressors
and longevity, which is mediated by the insulin-IGF-like signaling
pathway.},
url = {http://jcs.biologists.org/cgi/content/abstract/123/12/2124}
}
@ARTICLE{Twiner2008,
author = {Twiner, Michael J. and Ryan, James C. and Morey, Jeanine S. and Smith,
Kent J. and Hammad, Samar M. and Van Dolah, Frances M. and Hess,
Philipp and McMahon, Terry and Satake, Masayuki and Yasumoto, Takeshi
and Doucette, Gregory J.},
title = {Transcriptional profiling and inhibition of cholesterol biosynthesis
in human T lymphocyte cells by the marine toxin azaspiracid},
journal = {Genomics},
year = {2008},
volume = {91},
pages = {289--300},
number = {3},
month = mar,
abstract = {Azaspiracid-1 (AZA-1) is a marine biotoxin reported to accumulate
in shellfish from several countries, including eastern Canada, Morocco,
and much of western Europe, and is frequently associated with severe
gastrointestinal human intoxication. As the mechanism of action of
AZA-1 is currently unknown, human DNA microarrays and qPCR were used
to profile gene expression patterns in human T lymphocyte cells following
AZA-1 exposure. Some of the early (1 h) responding genes consisted
of transcription factors, membrane proteins, receptors, and inflammatory
genes. Four- and 24-h responding genes were dominated by genes involved
in de novo lipid biosynthesis of which 17 of 18 involved in cholesterol
biosynthesis were significantly up regulated. The up regulation of
synthesis genes was likely in response to the ca. 50% reduction in
cellular cholesterol, which correlated with up regulated protein
expression levels of the low-density lipoprotein receptor. These
data collectively detail the inhibition of de novo cholesterol synthesis,
which is the likely cause of cytotoxicity and potentially a target
pathway of the toxin.},
issn = {0888-7543},
keywords = {Azaspiracid-1, Cholesterol, Fatty acid, Gene expression, Harmful algal
bloom, Immunoblot, Low-density lipoprotein receptor, T lymphocyte
cells, Microarray, Shellfish toxin},
url = {http://www.sciencedirect.com/science/article/B6WG1-4RJSJ18-1/2/22854ca11306e239841630909fa3b1a7}
}
@ARTICLE{Tyburczy2010,
author = {Tyburczy, Magdalena Ewa and Kotulska, Katarzyna and Pokarowski, Piotr
and Mieczkowski, Jakub and Kucharska, Joanna and Grajkowska, Wieslawa
and Roszkowski, Maciej and Jozwiak, Sergiusz and Kaminska, Bozena},
title = {Novel Proteins Regulated by mTOR in Subependymal Giant Cell Astrocytomas
of Patients with Tuberous Sclerosis Complex and New Therapeutic Implications},
journal = {Am. J. Pathol.},
year = {2010},
volume = {176},
pages = {1878--1890},
number = {4},
month = apr,
abstract = {Subependymal giant cell astrocytomas (SEGAs) are rare brain tumors
associated with tuberous sclerosis complex (TSC), a disease caused
by mutations in TSC1 or TSC2, resulting in enhancement of mammalian
target of rapamycin (mTOR) activity, dysregulation of cell growth,
and tumorigenesis. Signaling via mTOR plays a role in multifaceted
genomic responses, but its effectors in the brain are largely unknown.
Therefore, gene expression profiling on four SEGAs was performed
with Affymetrix Human Genome arrays. Of the genes differentially
expressed in TSC, 11 were validated by real-time PCR on independent
tumor samples and 3 SEGA-derived cultures. Expression of several
proteins was confirmed by immunohistochemistry. The differentially-regulated
proteins were mainly involved in tumorigenesis and nervous system
development. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 genes
were likely to be mTOR effector genes in SEGA, as their expression
was modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells.
Inhibition of mTOR signaling affected size of cultured SEGA cells
but had no influence on their proliferation, morphology, or migration,
whereas inhibition of both mTOR and extracellular signal-regulated
kinase signaling pathways led to significant alterations of these
processes. For the first time, we identified genes related to the
occurrence of SEGA and regulated by mTOR and demonstrated an effective
modulation of SEGA growth by pharmacological inhibition of both mTOR
and extracellular signal-regulated kinase signaling pathways, which
could represent a novel therapeutic approach.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/176/4/1878}
}
@ARTICLE{Tydell2007,
author = {Tydell, C. Chace and David-Fung, Elizabeth-Sharon and Moore, Jonathan
E. and Rowen, Lee and Taghon, Tom and Rothenberg, Ellen V.},
title = {Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte
Developmental Pathway},
journal = {J. Immunol.},
year = {2007},
volume = {179},
pages = {421--438},
number = {1},
month = jul,
abstract = {Notch signaling activates T lineage differentiation from hemopoietic
progenitors, but relatively few regulators that initiate this program
have been identified, e.g., GATA3 and T cell factor-1 (TCF-1) (gene
name Tcf7). To identify additional regulators of T cell specification,
a cDNA library from mouse Pro-T cells was screened for genes that
are specifically up-regulated in intrathymic T cell precursors as
compared with myeloid progenitors. Over 90 genes of interest were
identified, and 35 of 44 tested were confirmed to be more highly
expressed in T lineage precursors relative to precursors of B and/or
myeloid lineage. To a remarkable extent, however, expression of these
T lineage-enriched genes, including zinc finger transcription factor,
helicase, and signaling adaptor genes, was also shared by stem cells
(Lin-Sca-1+Kit+CD27-) and multipotent progenitors (Lin-Sca-1+Kit+CD27+),
although down-regulated in other lineages. Thus, a major fraction
of these early T lineage genes are a regulatory legacy from stem
cells. The few genes sharply up-regulated between multipotent progenitors
and Pro-T cell stages included those encoding transcription factors
Bcl11b, TCF-1 (Tcf7), and HEBalt, Notch target Deltex1, Deltex3L,
Fkbp5, Eva1, and Tmem131. Like GATA3 and Deltex1, Bcl11b, Fkbp5,
and Eva1 were dependent on Notch/Delta signaling for induction in
fetal liver precursors, but only Bcl11b and HEBalt were up-regulated
between the first two stages of intrathymic T cell development (double
negative 1 and double negative 2) corresponding to T lineage specification.
Bcl11b was uniquely T lineage restricted and induced by Notch/Delta
signaling specifically upon entry into the T lineage differentiation
pathway.},
url = {http://www.jimmunol.org/cgi/content/abstract/179/1/421}
}
@ARTICLE{Tyekucheva2011,
author = {Tyekucheva, Svitlana and Yolken, Robert and McCombie, W and Parla,
Jennifer and Kramer, Melissa and Wheelan, Sarah and Sabunciyan, Sarven},
title = {Establishing the baseline level of repetitive element expression
in the human cortex},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {495},
number = {1},
abstract = {BACKGROUND:Although nearly half of the human genome is comprised of
repetitive sequences, the expression profile of these elements remains
largely uncharacterized. Recently developed high throughput sequencing
technologies provide us with a powerful new set of tools to study
repeat elements. Hence, we performed whole transcriptome sequencing
to investigate the expression of repetitive elements in human frontal
cortex using postmortem tissue obtained from the Stanley Medical
Research Institute.RESULTS:We found a significant amount of reads
from the human frontal cortex originate from repeat elements. We
also noticed that Alu elements were expressed at levels higher than
expected by random or background transcription. In contrast, L1 elements
were expressed at lower than expected amounts.CONCLUSIONS:Repetitive
elements are expressed abundantly in the human brain. This expression
pattern appears to be element specific and can not be explained by
random or background transcription. These results demonstrate that
our knowledge about repetitive elements is far from complete. Further
characterization is required to determine the mechanism, the control,
and the effects of repeat element expression.},
doi = {10.1186/1471-2164-12-495},
issn = {1471-2164},
pubmedid = {21985647},
url = {http://www.biomedcentral.com/1471-2164/12/495}
}
@ARTICLE{Tyler2010,
author = {Tyler, Andrea D. and Milgrom, Raquel and Xu, Wei and Stempak, Joanne
M. and Greenberg, Gordon R. and McLeod, Robin S. and Cohen, Zane
and Silverberg, Mark S.},
title = {W1214 Genetic Polymorphisms, Serum Anti-Flagellin and ASCA are Associated
With Outcome Following Ileal Pouch-Anal Anastomosis (IPAA)},
journal = {Gastroenterology},
year = {2010},
volume = {138},
pages = {S--675-S-676},
number = {5, Supplement 1},
month = may,
booktitle = {2010 DDW Abstract Supplement},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4YY8VGV-3Y0/2/a00ec7d706d719e7616c4e50b113b9c1}
}
@ARTICLE{Tyynismaa2010,
author = {Tyynismaa, Henna and Carroll, Christopher J. and Raimundo, Nuno and
Ahola-Erkkila, Sofia and Wenz, Tina and Ruhanen, Heini and Guse,
Kilian and Hemminki, Akseli and Peltola-Mjosund, Katja E. and Tulkki,
Valtteri and Oresic, Matej and Moraes, Carlos T. and Pietilainen,
Kirsi and Hovatta, Iiris and Suomalainen, Anu},
title = {Mitochondrial myopathy induces a starvation-like response},
journal = {Hum. Mol. Genet.},
year = {2010},
volume = {19},
pages = {3948--3958},
number = {20},
month = oct,
abstract = {Mitochondrial respiratory chain (RC) deficiency is among the most
common causes of inherited metabolic disease, but its physiological
consequences are poorly characterized. We studied the skeletal muscle
gene expression profiles of mice with late-onset mitochondrial myopathy.
These animals express a dominant patient mutation in the mitochondrial
replicative helicase Twinkle, leading to accumulation of multiple
mtDNA deletions and progressive subtle RC deficiency in the skeletal
muscle. The global gene expression pattern of the mouse skeletal
muscle showed induction of pathways involved in amino acid starvation
response and activation of Akt signaling. Furthermore, the muscle
showed induction of a fasting-related hormone, fibroblast growth
factor 21 (Fgf21). This secreted regulator of lipid metabolism was
also elevated in the mouse serum, and the animals showed widespread
changes in their lipid metabolism: small adipocyte size, low fat
content in the liver and resistance to high-fat diet. We propose
that RC deficiency induces a mitochondrial stress response, with
local and global changes mimicking starvation, in a normal nutritional
state. These results may have important implications for understanding
the metabolic consequences of mitochondrial myopathies.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/19/20/3948}
}
@ARTICLE{Toelle2009,
author = {Tölle, Angelika and Jung, Monika and Lein, Michael and Johannsen,
Manfred and Miller, Kurt and Moch, Holger and Jung, Klaus and Kristiansen,
Glen},
title = {Brain-type and liver-type fatty acid-binding proteins: new tumor
markers for renal cancer?},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {248},
number = {1},
abstract = {BACKGROUND:Renal cell carcinoma (RCC) is the most common renal neoplasm.
Cancer tissue is often characterized by altered energy regulation.
Fatty acid-binding proteins (FABP) are involved in the intracellular
transport of fatty acids (FA). We examined the level of brain-type
(B) and liver-type (L) FABP mRNA and the protein expression profiles
of both FABPs in renal cell carcinoma.METHODS:Paired tissue samples
of cancerous and noncancerous kidney parts were investigated. Quantitative
RT-PCR, immunohistochemistry and western blotting were used to determine
B- and L-FABP in tumor and normal tissues. The tissue microarray
(TMA) contained 272 clinico-pathologically characterized renal cell
carcinomas of the clear cell, papillary and chromophobe subtype.
SPSS 17.0 was used to apply crosstables (?2-test), correlations and
survival analyses.RESULTS:B-FABP mRNA was significantly up-regulated
in renal cell carcinoma. In normal tissue B-FABP mRNA was very low
or often not detectable. RCC with a high tumor grading (G3 + G4)
showed significantly lower B-FABP mRNA compared with those with a
low grading (G1 + G2). Western blotting analysis detected B-FABP
in 78% of the cases with a very strong band but in the corresponding
normal tissue it was weak or not detectable. L-FABP showed an inverse
relationship for mRNA quantification and western blotting. A strong
B-FABP staining was present in 52% of the tumor tissues contained
in the TMA. In normal renal tissue, L-FABP showed a moderate to strong
immunoreactivity in proximal tubuli. L-FABP was expressed at lower
rates compared with the normal tissues in 30.5% of all tumors. There
was no correlation between patient survival times and the staining
intensity of both FABPs.CONCLUSION:While B-FABP is over expressed
in renal cell carcinoma in comparison to normal renal tissues L-FABP
appears to be reduced in tumor tissue. Although the expression behavior
was not related to the survival outcome of the RCC patients, it can
be assumed that these changes indicate fundamental alterations in
the fatty metabolism in the RCC carcinogenesis. Further studies should
identify the role of both FABPs in carcinogenesis, progression and
with regard to a potential target in RCC.},
doi = {10.1186/1471-2407-9-248},
issn = {1471-2407},
pubmedid = {19622156},
url = {http://www.biomedcentral.com/1471-2407/9/248}
}
@ARTICLE{U2001,
author = {U, Mami and Miyashita, Toshiyuki and Shikama, Yoshiaki and Tadokoro,
Keiko and Yamada, Masao},
title = {Molecular cloning and characterization of six novel isoforms of human
Bim, a member of the proapoptotic Bcl-2 family},
journal = {FEBS Letters},
year = {2001},
volume = {509},
pages = {135--141},
number = {1},
month = nov,
abstract = {Bim protein is one of the BH3-only proteins, members of the Bcl-2
family that have only one of the Bcl-2 homology regions, BH3. BH3-only
proteins are essential initiators of apoptotic cell death. Thus far,
three isoforms of Bim have been reported, i.e. BimEL, BimL and BimS.
Here we report the cloning and characterization of six novel isoforms
of human Bim, designated as Bim[alpha]1, [alpha]2, and [beta]1-[beta]4,
which are generated by alternative splicing. Unlike the three known
isoforms, none of these novel isoforms contained a C-terminal hydrophobic
region. Among the novel isoforms, only Bim[alpha]1 and [alpha]2 contained
a BH3 domain and were proapoptotic, although less potent than the
classical isoforms. These two isoforms localized, at least in part,
in mitochondria when transiently expressed in HeLa cells as a green
fluorescent protein-fused form. These results suggest that the BH3
domain is necessary for induction of apoptosis and mitochondrial
localization but not sufficient for the full proapoptotic activity.
While the classical isoforms were always predominantly expressed
in transformed cells, expression profiles of bim isoforms were highly
variable among normal tissues at least in humans, suggesting a tissue-specific
transcriptional regulation of bim.},
issn = {0014-5793},
keywords = {Apoptosis, Mitochondrion, Bim, Alternative splicing},
url = {http://www.sciencedirect.com/science/article/B6T36-44GMKTN-1/2/c30ce86363d503f3faf4a271372e1463}
}
@ARTICLE{Ubagai2010,
author = {Ubagai, Tsuneyuki and Kikuchi, Takane and Fukusato, Toshio and Ono,
Yasuo},
title = {Aflatoxin B1 modulates the insulin-like growth factor-2 dependent
signaling axis},
journal = {Toxicology in Vitro},
year = {2010},
volume = {24},
pages = {783--789},
number = {3},
month = apr,
abstract = {Although aflatoxin B1 (AFB1) is known as a mycotoxin that induces
hepatocellular carcinoma (HCC), its effects on HCC cells have not
been sufficiently investigated. The HCC cell lines HepG2, Huh-6,
Huh-7, and PLC were cultured (5 × 105 cells/ml) and various concentrations
of AFB1 were added. The expression levels of the [alpha]-fetoprotein
(AFP), insulin-like growth factor-2 (IGF-2), and insulin-like growth
factor-1 receptor (IGF-1R) genes in each sample were determined by
real-time PCR, with the following results: (1) The level of AFP expression
in HepG2 increased at 5-50 ng/ml of AFB1 in a dose-dependent manner.
The AFP expression level in Huh-6 increased at 0.01-5 ng/ml of AFB1
in a dose-dependent manner and decreased to half controls level at
50 ng/ml of AFB1. The AFP expression level in Huh-7 decreased to
one-third the original level at 0.5-50 ng/ml of AFB1. The AFP expression
level in PLC decreased at 0-0.5 ng/ml of AFB1 in a dose-dependent
manner, and decreased to one-third at concentrations of AFB1 between
0.5 and 50 ng/ml. (2) The IGF-2 and IGF-1R expression levels in Huh-6
increased more than 10-fold at 0.5-5 ng/ml of AFB1, but decreased
to half at 50 ng/ml of AFB1. The IGF-2 and IGF-1R expression levels
in other cell lines increased in a dose-dependent manner. AFB1 induced
translations of IGF-2 and IGF-1R and cell proliferation: When 50 ng/ml
AFB1 was administrated, cell numbers were 2.0-, 1.7-, and 1.5-fold
higher than those of controls after 3 days of culture in HepG2, Huh-7,
and PLC, respectively. Particularly, in Huh-6, it increased 2.5-fold
higher than those of controls following 5 ng/ml AFB1 administration.
The ratio of fold-change phospho-IGF-1R in all cell lines that were
treated with AFB1, increased 1.1-1.5-fold. These results indicate
that AFB1 may enhance HCC cell proliferation through an IGF-2-dependent
signal axis, although it remains to be investigated whether those
effects are associated with human hepatocarcinogenesis resulting
from AFB1 exposure.},
issn = {0887-2333},
keywords = {Aflatoxin B1, Hepatocellular carcinoma, [alpha]-Fetoprotein, Insulin-like
growth factor-2, Insulin-like growth factor-1 receptor, qPCR},
url = {http://www.sciencedirect.com/science/article/B6TCP-4Y1VSF9-5/2/a4b9e90051768d47d3de2c40052032bc}
}
@ARTICLE{Ubagai2008,
author = {Ubagai, Tsuneyuki and Tansho, Shigeru and Ito, Tadashi and Ono, Yasuo},
title = {Influences of aflatoxin B1 on reactive oxygen species generation
and chemotaxis of human polymorphonuclear leukocytes},
journal = {Toxicology in Vitro},
year = {2008},
volume = {22},
pages = {1115--1120},
number = {4},
month = jun,
abstract = {The effects of aflatoxin (AF), a hepatotoxic agent and the strongest
carcinogen in nature, on polymorphonuclear leukocyte (PMN) chemotaxis
and chemiluminescence (CL) were studied. Luminol-dependent CL activity,
which reflects the production of reactive oxygen species (ROS) from
PMNs, was up-regulated to ~150% when PMNs were treated with 0.05 ng/ml
of AFB1 upon stimulation with N-formyl-methionine-leucine-phenylalanine
(fMLP) or zymosan. On the other hand, PMN CL activity was down-regulated
to ~25% of the control when PMNs were treated with 50 ng/ml of AFB1
upon stimulation with zymosan. The effect of AFB1 on PMN chemotaxis
was also investigated using the Boyden chamber method. The chemotactic
ability of PMNs when interleukin (IL)-8 was used as a chemoattractant
was inhibited in a dose-dependent manner at AFB1 concentrations of
>10 ng/ml. In reverse transcriptase (RT)-PCR analysis, gene expression
levels of CXC chemokine receptor (CXCR)1/2, whose ligands are IL-8,
granulocyte chemotactic protein (GCP)-2, neutrophil attractant-activation
protein (NAP)-2, and epithelial neutrophil-activating protein (ENA)-78,
which regulate PMN chemotaxis, were also down-regulated in a dose-dependent
manner by 50 ng/ml AFB1. mRNA expression levels of CXCR1/2 were down-regulated
to ~85% of that in the controls when PMNs were treated with 100 ng/ml
AFB1. These results suggest that a high concentration of AFB1 reduces
the chemotactic ability of PMNs via the CXCR1/2 cascade indirectly.},
issn = {0887-2333},
keywords = {Aflatoxin B1, Polymorphonuclear leukocytes, Chemiluminescence, Chemotaxis,
RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6TCP-4RP0MJV-1/2/762a97b7d1e1d512001af82aec778194}
}
@ARTICLE{Ubeda2008,
author = {Ubeda, Jean-Michel and Légaré, Danielle and Raymond, Frédéric and
Ouameur, Amin and Boisvert, Sébastien and Rigault, Philippe and Corbeil,
Jacques and Tremblay, Michel and Olivier, Martin and Papadopoulou,
Barbara and Ouellette, Marc},
title = {Modulation of gene expression in drug resistant Leishmania is associated
with gene amplification, gene deletion and chromosome aneuploidy},
journal = {Genome Biology},
year = {2008},
volume = {9},
pages = {R115},
number = {7},
abstract = {BACKGROUND:Drug resistance can be complex, and several mutations responsible
for it can co-exist in a resistant cell. Transcriptional profiling
is ideally suited for studying complex resistance genotypes and has
the potential to lead to novel discoveries. We generated full genome
70-mer oligonucleotide microarrays for all protein coding genes of
the human protozoan parasites Leishmania major and Leishmania infantum.
These arrays were used to monitor gene expression in methotrexate
resistant parasites.RESULTS:Leishmania is a eukaryotic organism with
minimal control at the level of transcription initiation and few
genes were differentially expressed without concomitant changes in
DNA copy number. One exception was found in Leishmania major, where
the expression of whole chromosomes was down-regulated. The microarrays
highlighted several mechanisms by which the copy number of genes
involved in resistance was altered; these include gene deletion,
formation of extrachromosomal circular or linear amplicons, and the
presence of supernumerary chromosomes. In the case of gene deletion
or gene amplification, the rearrangements have occurred at the sites
of repeated (direct or inverted) sequences. These repeats appear
highly conserved in both species to facilitate the amplification
of key genes during environmental changes. When direct or inverted
repeats are absent in the vicinity of a gene conferring a selective
advantage, Leishmania will resort to supernumerary chromosomes to
increase the levels of a gene product.CONCLUSION:Aneuploidy has been
suggested as an important cause of drug resistance in several organisms
and additional studies should reveal the potential importance of
this phenomenon in drug resistance in Leishmania.},
doi = {10.1186/gb-2008-9-7-r115},
issn = {1465-6906},
pubmedid = {18638379},
url = {http://genomebiology.com/content/9/7/R115}
}
@ARTICLE{Uchida2010,
author = {Uchida, Hiroshi and Yamazaki, Ken and Fukuma, Mariko and Yamada,
Taketo and Hayashida, Tetsu and Hasegawa, Hirotoshi and Kitajima,
Masaki and Kitagawa, Yuko and Sakamoto, Michiie},
title = {Overexpression of leucine-rich repeat-containing G protein-coupled
receptor 5 in colorectal cancer},
journal = {Cancer Science},
year = {2010},
volume = {101},
pages = {1731--1737},
number = {7},
abstract = {Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)
is a 7-transmembrane receptor reportedly expressed in stem cells
of the intestinal crypts and hair follicles of mice. Overexpression
of LGR5 is observed in some types of cancer; however, there has been
no specific assessment in colorectal tumorigenesis. We performed
quantitative RT-PCR for LGR5 expression in 37 representative cancer
cell lines, and showed that LGR5 mRNA was frequently overexpressed
in colon cancer cell lines. Moreover, LGR5 expression was higher
in colon cancer cell lines derived from metastatic tumors compared
with those from primary tumors. In clinical specimens, there was
significant overexpression of LGR5 in 35 of 50 colorectal cancers
(CRCs), and in seven of seven sporadic colonic adenomas, compared
with matched normal mucosa. This suggests up-regulation of LGR5 from
the early stage of colorectal tumorigenesis. LGR5 expression showed
marked variation among CRC cases and correlated significantly with
lymphatic invasion, vascular invasion, tumor depth, lymph node metastasis,
and tumor stage (IIIC vs. IIIB). In addition to cancer cells, crypt
base columnar cells of the small intestine and colon were shown by
in situ hybridization to express LGR5. This is the first report suggesting
the involvement of LGR5, not only in early events but also in late
events in colorectal tumorigenesis. (Cancer Sci 2010)},
issn = {1349-7006},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1349-7006.2010.01571.x}
}
@ARTICLE{Uchida2010a,
author = {Uchida, Kenzo and Nakajima, Hideaki and Hirai, Takayuki and Yayama,
Takafumi and Chen, Ke-Bing and Kobayashi, Shigeru and Roberts, Sally
and Johnson, William and Baba, Hisatoshi},
title = {Microarray analysis of expression of cell death-associated genes
in rat spinal cord cells exposed to cyclic tensile stresses in vitro},
journal = {BMC Neuroscience},
year = {2010},
volume = {11},
pages = {84},
number = {1},
abstract = {BACKGROUND:The application of mechanical insults to the spinal cord
results in profound cellular and molecular changes, including the
induction of neuronal cell death and altered gene expression profiles.
Previous studies have described alterations in gene expression following
spinal cord injury, but the specificity of this response to mechanical
stimuli is difficult to investigate in vivo. Therefore, we have investigated
the effect of cyclic tensile stresses on cultured spinal cord cells
from E15 Sprague-Dawley rats, using the FX3000® Flexercell Strain
Unit. We examined cell morphology and viability over a 72 hour time
course. Microarray analysis of gene expression was performed using
the Affymetrix GeneChip System®, where categorization of identified
genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia
of Genes and Genomes (KEGG) systems. Changes in expression of 12
genes were validated with quantitative real-time reverse transcription
polymerase chain reaction (RT-PCR).RESULTS:The application of cyclic
tensile stress reduced the viability of cultured spinal cord cells
significantly in a dose- and time-dependent manner. Increasing either
the strain or the strain rate independently was associated with significant
decreases in spinal cord cell survival. There was no clear evidence
of additive effects of strain level with strain rate. GO analysis
identified 44 candidate genes which were significantly related to
"apoptosis" and 17 genes related to "response to stimulus". KEGG
analysis identified changes in the expression levels of 12 genes
of the mitogen-activated protein kinase (MAPK) signaling pathway,
which were confirmed to be upregulated by RT-PCR analysis.CONCLUSIONS:We
have demonstrated that spinal cord cells undergo cell death in response
to cyclic tensile stresses, which were dose- and time-dependent.
In addition, we have identified the up regulation of various genes,
in particular of the MAPK pathway, which may be involved in this
cellular response. These data may prove useful, as the accurate knowledge
of neuronal gene expression in response to cyclic tensile stress
will help in the development of molecular-based therapies for spinal
cord injury.},
doi = {10.1186/1471-2202-11-84},
issn = {1471-2202},
pubmedid = {20663127},
url = {http://www.biomedcentral.com/1471-2202/11/84}
}
@ARTICLE{Uchida2011,
author = {Uchida, Yousuke and Chiyomaru, Takeshi and Enokida, Hideki and Kawakami,
Kazumori and Tatarano, Shuichi and Kawahara, Kazuya and Nishiyama,
Kenryu and Seki, Naohiko and Nakagawa, Masayuki},
title = {MiR-133a induces apoptosis through direct regulation of GSTP1 in
bladder cancer cell lines},
journal = {Urologic Oncology: Seminars and Original Investigations},
year = {2011},
volume = {In Press, Corrected Proof},
pages = {--},
abstract = {Objective: We previously demonstrated that miR-133a is a tumor-suppressive
microRNA (miRNA) and is commonly down-regulated in human bladder
cancer (BC). The aim of this study is to determine a novel oncogenic
gene targeted by miR-133a in BC.Methods: To identify genes targeted
by miR-133a, an oligo-microarray analysis was performed using the
miR-133a-transfected BC cell lines. For gain/loss-of-function studies,
miR-133a/si-glutathione S-transferase [pi]1 (GSTP1)-transfectants
were subjected to XTT assay and flow cytometry to evaluate their
cell viability and apoptosis status. The luciferase reporter assay
was used to confirm the actual binding sites between miR-133a and
GSTP1 mRNA. The mRNA and protein expression of GSTP1 in BC cell lines
and clinical samples were evaluated by real-time RT-PCR and Western
blot, respectively.Results: MiR-133a transfection induced cell viability
inhibition and apoptosis in BC cell lines. We focused on the GSTP1
gene that was the top 7 down-regulated one in the gene profile from
the miR-133a-transfectants. MiR-133a transfection repressed expression
levels of mRNA and protein levels of GSTP1. A luciferase reporter
assay suggested that the actual binding may occur between miR-133a
and GSTP1 mRNA. Cell viability inhibition and apoptosis were induced
in the si-GSTP1 transfectants compared with the controls (P < 0.005).
GSTP1 mRNA expression levels in 43 clinical BCs were significantly
higher than those in eight normal bladder epitheliums (P = 0.0277).Conclusion:
Our data suggest that tumor suppressive miR-133a directly regulated
oncogenic GSTP1 gene in BC, and that an anti-apoptotic effect mediated
by GSTP1 is maintained by miR-133a down-regulation in human BC.},
issn = {1078-1439},
keywords = {Bladder cancer, GSTP1, microRNA, Apoptosis},
url = {http://www.sciencedirect.com/science/article/pii/S107814391000298X}
}
@ARTICLE{Uchiyama2008,
author = {Uchiyama, Yasushi and Yoshida, Hiroto and Koike, Nobuo and Hayakawa,
Naohiko and Sugita, Atsuko and Nishimura, Takashi and Mihara, Masahiko},
title = {Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade
of IL-6 clearance, but not via the induction of IL-6 production},
journal = {International Immunopharmacology},
year = {2008},
volume = {8},
pages = {1595--1601},
number = {11},
month = nov,
abstract = {We explored the mechanism for the increase of blood IL-6 level after
anti-IL-6 receptor (IL-6R) antibody injection. First, we examined
whether anti-IL-6R antibody stimulates IL-6 production. Single injection
of tocilizumab (anti-IL-6R antibody) in monkeys with collagen-induced
arthritis (CIA) caused a marked increase in blood IL-6 and IL-6R
levels, but did not increase IL-6 mRNA and IL-6R mRNA expression
in liver, spleen, lymph nodes, synovium or whole blood 1, 3 and 7 days
later. This suggests that tocilizumab did not induce IL-6 and IL-6R
production. Second, we investigated whether anti-IL-6R antibody releases
IL-6 from IL-6 complexes in the blood. When plasma from CIA monkeys
was incubated with tocilizumab, the IL-6 concentration was not affected.
Finally, we studied whether anti-IL-6R antibody affects the clearance
of IL-6 from the blood. When MR16-1 (anti-mouse IL-6R antibody) was
injected into IL-6-deficient mice continuously infused with human
IL-6, blood human IL-6 levels significantly increased. These results
suggest that the elevation of blood IL-6 after the administration
of anti-IL-6R antibody is the result of inhibition of the clearance
of IL-6 due to IL-6R blockade, and that it is not the result of induction
of IL-6 production or release of IL-6 from complexes.},
issn = {1567-5769},
keywords = {Anti-IL-6R antibody, IL-6, Soluble IL-6R, Clearance, Protein synthesis},
url = {http://www.sciencedirect.com/science/article/B6W7N-4T2XTWV-2/2/944a4ec1c6f500d9cc51b5d86b57ebaa}
}
@ARTICLE{Uchizono2009,
author = {Uchizono, Yuji and Baldwin, Aaron C. and Sakuma, Hiroya and Pugh,
William and Polonsky, Kenneth S. and Hara, Manami},
title = {Role of HNF-1[alpha] in regulating the expression of genes involved
in cellular growth and proliferation in pancreatic beta-cells},
journal = {Diabetes Research and Clinical Practice},
year = {2009},
volume = {84},
pages = {19--26},
number = {1},
month = apr,
abstract = {Hepatocyte nuclear factor (HNF)-1[alpha] is a homeodomain-containing
transcription factor. Humans heterozygous for mutations in the HNF-1[alpha]
gene develop maturity-onset diabetes of the young (MODY3), which
is associated with reduced insulin secretion. The mechanisms responsible
for defective glucose-induced insulin secretion due to HNF-1[alpha]
deficiency are complex. In order to explore the relationship between
HNF-1[alpha] and beta-cell proliferation, we have created a novel
animal model. Mice lacking one allele of the HNF-1[alpha] gene were
crossed with transgenic mice expressing the large T antigen driven
by the rat insulin II promoter (RIP). The resulting mouse strains
allowed us to study the effect of HNF-1[alpha] deficiency on the
extensive beta-cell proliferation that occurs in these mice. Our
results indicate that deficiency of HNF-1[alpha] severely constrains
the extent of beta-cell proliferation occurring in RIP-Tag mice leading
to significant changes in blood glucose concentrations as a result
of reduced beta-cell number, insulin content, insulin secretion and
intracellular responses in Ca2+. Furthermore expression profiling
studies using immortalized cell lines generated from HNF-1[alpha]/RIP-Tag
mice showed changes in expression of genes involved in cellular growth
and proliferation. These results provide insights into the mechanisms
whereby HNF-1[alpha] affects beta-cell function.},
issn = {0168-8227},
keywords = {Hepatocyte nuclear factor-1[alpha], Maturity-onset diabetes of the
young, Pancreatic beta-cells, Diabetes, Expression profiling},
url = {http://www.sciencedirect.com/science/article/B6T5Y-4VH32X0-2/2/31cfb02f1f36e5a7112f043683929905}
}
@ARTICLE{Udall2006,
author = {Udall, Joshua A. and Swanson, Jordan M. and Nettleton, Dan and Percifield,
Ryan J. and Wendel, Jonathan F.},
title = {A Novel Approach for Characterizing Expression Levels of Genes Duplicated
by Polyploidy},
journal = {Genetics},
year = {2006},
volume = {173},
pages = {1823--1827},
number = {3},
month = jul,
abstract = {Studying gene expression in polyploids is complicated by genomewide
gene duplication and the problem of distinguishing transcript pools
derived from each of the two homeologous genomes such as the A- and
D-genomes of allotetraploid Gossypium. Short oligonucleotide probes
designed to specifically target several hundred homeologous gene
pairs of Gossypium were printed on custom NimbleGen microarrays.
These results demonstrate that relative expression levels of homeologous
genes may be measured by microarrays and that deviation from equal
expression levels of homeologous loci may be common in the allotetraploid
nucleus of Gossypium.},
url = {http://www.genetics.org/cgi/content/abstract/173/3/1823}
}
@ARTICLE{Udar2006,
author = {Udar, Nitin and Atilano, Shari R. and Brown, Donald J. and Holguin,
Bret and Small, Kent and Nesburn, Anthony B. and Kenney, M. Cristina},
title = {SOD1: A Candidate Gene for Keratoconus},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2006},
volume = {47},
pages = {3345--3351},
number = {8},
month = aug,
abstract = {PURPOSE. To screen superoxide dismutase 1 (SOD1) on chromosome 21
as a possible candidate gene for familial keratoconus (KC). METHODS.
Total genomic DNA was extracted from the blood of 15 different KC
families and 156 unaffected subjects. All five exons of the SOD1
gene were sequenced. For a rapid screening test, DNA was amplified
by polymerase chain reaction (PCR), digested with HpyCH4 III or analyzed
by radioactively end-labeled exon PCR. RNA was extracted from leukocytes
and reverse transcribed to cDNA, and the PCR was amplified for splice
variants. Some samples were cloned and sequenced. RESULTS. A heterozygous
genomic 7-base deletion in intron 2 of the SOD1 gene was identified
in two KC families (pedigrees 1 and 6). The deletion segregated within
pedigree 1 and was absent in 312 chromosomes from normal individuals.
RNA from the proband of pedigree 1 showed that in addition to the
wild-type transcript, two other transcripts were expressed for the
CuZn SOD (SOD1) gene: lacking entire exon 2 (LE2) and lacking entire
exon 2 and entire exon 3 (LE2E3). CONCLUSIONS. A unique genomic deletion
within intron 2 close to the 5' splice junction of the SOD1 gene
was identified in three patients with KC. Moreover, mRNA from one
affected individual also had two transcript splice variants (LE2
and LE2E3) that others have shown to code for proteins lacking the
active site of the SOD1 enzyme. Further studies should be conducted
to determine whether a causal relationship exists between these two
events that may increase oxidative stress and be associated with
KC.},
url = {http://www.iovs.org/cgi/content/abstract/47/8/3345}
}
@ARTICLE{Udvardi2008,
author = {Udvardi, Michael K. and Czechowski, Tomasz and Scheible, Wolf-Rudiger},
title = {Eleven Golden Rules of Quantitative RT-PCR},
journal = {PLANT CELL},
year = {2008},
volume = {20},
pages = {1736--1737},
number = {7},
month = jul,
url = {http://www.plantcell.org}
}
@ARTICLE{Ueda2009,
author = {Ueda, Tomohiro and Nakagawa, Masayuki and Okamura, Motohiro and Tanoue,
Hideki and Yoshimura, Naoki},
title = {Urine alkalinization improves the problems of pain and sleep in patients
with interstitial cystitis},
journal = {The Journal of Urology},
year = {2009},
volume = {181},
pages = {22--23},
number = {4, Supplement 1},
month = apr,
booktitle = {AUA Annual Meeting Program Abstracts, 2009 AUA Annual Meeting},
issn = {0022-5347},
url = {http://www.sciencedirect.com/science/article/B7XMT-4VTWN64-2B/2/213e49b0d4a1c199d4c992c1354aef2f}
}
@ARTICLE{Ueda2011,
author = {Ueda, Yukiko and Hajri, Tahar and Peng, DunFa and Marks-Shulman,
Pamela A. and Tamboli, Robyn A. and Shukrallah, Bassam and Saliba,
Jabbar and Jabbour, Kareem and El-Rifai, Wael and Abumrad, Nada A.
and Abumrad, Naji N.},
title = {Reduction of 8-iso-Prostaglandin F2[alpha] in the First Week After
Roux-en-Y Gastric Bypass Surgery},
journal = {Obesity},
year = {2011},
pages = {--},
month = apr,
issn = {1930-739X},
publisher = {The Obesity Society},
url = {http://dx.doi.org/10.1038/oby.2011.58}
}
@ARTICLE{Ueda2010,
author = {Ueda, Yoshiyasu and Kayama, Hisako and Jeon, Seong Gyu and Kusu,
Takashi and Isaka, Yoshitaka and Rakugi, Hiromi and Yamamoto, Masahiro
and Takeda, Kiyoshi},
title = {Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages
via the production of IL-10},
journal = {Int. Immunol.},
year = {2010},
volume = {22},
pages = {953--962},
number = {12},
month = dec,
abstract = {Several subsets of innate immune cells, all with unique properties,
reside within the intestinal lamina propria. However, compared with
intestinal dendritic cells (DCs), intestinal macrophages are less
well characterized. In this study, we examined the properties of
macrophages in the colonic lamina propria (LM{phi}). Colonic DCs
(LDC) showed LPS-induced production of IL-12p40. In contrast, LM{phi}
showed constitutive IL-10 production and unresponsiveness to LPS
in terms of inflammatory cytokine production. Comparison of the gene
expression profiles between LM{phi} and LDC revealed that LM{phi}
preferentially expressed IL-10-related genes. LM{phi} obtained from
mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis
factor (TNF)-{alpha} and IL-6 in response to LPS. IL-10 production
in the large intestine was mainly induced by LM{phi} and regulatory
T cells and was dependent on the presence of commensal microbiota.
Accordingly, LM{phi} from germ-free mice showed less production of
IL-10 and increased levels of LPS-induced TNF-{alpha} and IL-6 production.
Taken together, these results demonstrate that the activity of LM{phi}
to produce pro-inflammatory cytokines is negatively regulated through
commensal microbiota-dependent IL-10 production in the large intestine.},
comment = {10.1093/intimm/dxq449},
url = {http://intimm.oxfordjournals.org/cgi/content/abstract/22/12/953}
}
@ARTICLE{Ueda2011a,
author = {Yuto Ueda and Toshio Kojima and Taneaki Oikawa},
title = {Hippocampal gene network analysis suggests that coral calcium hydride
may reduce accelerated senescence in mice},
journal = {Nutrition Research},
year = {2011},
volume = {31},
pages = {863 - 872},
number = {11},
abstract = {Recent studies strongly support the hypothesis that an antioxidant
diet inhibits the pathologic aging process as shown in senescence-accelerated
mouse prone 8 (SAM/P-8). In our previous study in coral calcium hydride
(CCH), we reported that a diet rich in antioxidants inhibited the
pathologic aging process, increased the endogenous antioxidant ability,
and contributed to prolonging the lifespan of SAM/P-8. To test the
hypothesis that antioxidant CCH supplementation to SAM/P-8 mice would
change the gene expression and to understand how CCH reverses the
acceleration of aging in SAM/P-8 mice, we used a DNA array to compare
the expression levels in the hippocampus of the brains from 16-week-old
SAM/P-8 mice that were either treated or not treated with CCH. The
most significant up-regulated changes in the gene network of SAM/P-8
mice were free radical scavenging and molecular transport, whereas
genes associated with cell death, cancer, and cell cycle were down-regulated.
Our findings regarding the changes in these messenger RNA might be
associated with the inhibition of the acceleration of aging, as observed
in SAM/P-8 mice fed a CCH diet.},
doi = {10.1016/j.nutres.2011.09.011},
issn = {0271-5317},
keywords = {Senescence-accelerated mouse prone 8 (SAM/P-8)},
url = {http://www.sciencedirect.com/science/article/pii/S0271531711001825}
}
@ARTICLE{Uehara2011,
author = {Uehara, Takeki and Kondo, Chiaki and Yamate, Jyoji and Torii, Mikinori
and Maruyama, Toshiyuki},
title = {A toxicogenomic approach for identifying biomarkers for myelosuppressive
anemia in rats},
journal = {Toxicology},
year = {2011},
volume = {282},
pages = {139--145},
number = {3},
month = apr,
abstract = {Myelosuppressive anemia is a serious side effect associated with several
drugs. Thus, there is an increasing demand for sensitive biomarkers
for the early detection of myelosuppressive anemia during toxicological
studies. We applied a toxicogenomic approach to identify useful biomarker
genes reflecting myelosuppressive anemia in the rat liver. Expression
of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase
2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed
as a result of anemia induced by the myelosuppressive agents linezolid,
cisplatin, and carboplatin, suggesting that these genes may be suitable
biomarkers. Moreover, evaluation of perfused and unperfused livers
indicated that changes in the expression of these genes originate
in circulating reticulocytes in the liver. Erythroid differentiation-associated
changes in expression of the Hbb, Alas2, and Cdc25b genes were confirmed
in vitro using Friend leukemia cells. In conclusion, our current
research provides novel evidence that gene expression in circulating
reticulocytes contained in the liver changes dramatically under myelosuppressive
conditions. While further large-scale validation studies are needed,
our results indicate that the genes we identified might be useful
biomarkers for the sensitive detection of myelosuppressive anemia
in rats.},
issn = {0300-483X},
keywords = {Toxicogenomics, DNA microarray, Myelosuppressive anemia},
url = {http://www.sciencedirect.com/science/article/pii/S0300483X11000461}
}
@ARTICLE{Uehara2007,
author = {Uehara, Takeki and Miyoshi, Takako and Tsuchiya, Noriko and Masuno,
Koichi and Okada, Manabu and Inoue, Satoshi and Torii, Mikinori and
Yamate, Jyoji and Maruyama, Toshiyuki},
title = {Comparative analysis of gene expression between renal cortex and
papilla in nedaplatin-induced nephrotoxicity in rats},
journal = {Human and Experimental Toxicology},
year = {2007},
volume = {26},
pages = {767--780},
number = {10},
month = oct,
abstract = {To elucidate the mechanism of nephrotoxicity caused by anti-neoplastic
platinum complex, nedaplatin (NDP), treatment with a particular focus
on the renal papillary toxicity, we analysed the gene expression
profiles of two renal regions, the cortex (RC) and the papilla (RP)
in rat kidneys. Male Wistar rats received a single administration
of 10 mg/kg intravenous NDP or vehicle alone (5% xylitol solution)
and were sacrificed six days later. The kidneys were dissected into
the RC and RP and used for histopathological and microarray analyses.
Histopathologically, NDP caused characteristic renal lesions, such
as necrosis, single cell necrosis (with TUNEL TdT-mediated dUTP-biotin
nick end labelling-positive) and regeneration/hyperplasia of the
epithelial cells in both renal regions. Global gene expression analysis
revealed that several genes involved in various functional categories
were commonly deregulated in both renal regions, such as apoptosis,
cell cycle regulation, DNA metabolism, cell migration/adhesion and
cytoskeleton organization or genes induced as a perturbation of oxidative
status and calcium homeostasis. Comparative analysis of gene expression
between RC and RP revealed that genes encoding several subtypes of
cytokeratins were identified as being specifically overexpressed
in RP by the NDP treatment. Differential expression patterns of these
selected genes observed by microarray analysis were further confirmed
by quantitative real time RT-PCR and immunohistochemistry, which
demonstrated increased expression of cytokeratins (CKs) 14 and 19
at the epithelium covering RP and/or collecting duct epithelium.
Overall, the results contribute to understanding the renal molecular
events of NDP-induced nephrotoxicity including novel potential biomarker
genes encoding CKs 14 and 19 that may serve as indicators of renal
papillary toxicity. Human & Experimental Toxicology (2007) 26, 767--780},
url = {http://het.sagepub.com/cgi/content/abstract/26/10/767}
}
@ARTICLE{Ueki2009,
author = {Ueki, Iori and Giesy, Sarah L. and Harvatine, Kevin J. and Kim, Jin
Wook and Boisclair, Yves R.},
title = {The Acid-Labile Subunit Is Required for Full Effects of Exogenous
Growth Hormone on Growth and Carbohydrate Metabolism},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {3145--3152},
number = {7},
month = jul,
abstract = {Normal postnatal growth is dependent in part on overlapping actions
of GH and IGF-I. These actions reflect GH stimulation of IGF-I production
in liver and extrahepatic tissues, representing respectively the
endocrine and autocrine/paracrine arms of the IGF system. Recent
experiments in genetically modified mice show that each source of
IGF-I can compensate for absence of the other but do not resolve
their relative role in postnatal growth. In an effort to address
this issue, we studied the GH responsiveness of mice harboring a
null mutation of the acid-labile subunit (ALS). Null ALS mice have
a substantial reduction in endocrine IGF-I but, unlike other models
of plasma IGF-I deficiency, have no obvious additional endocrine
defects. Wild type and null ALS mice of both sexes received daily
sc injections of saline or recombinant bovine GH between d 35 and
63 of postnatal age. The GH-stimulated body weight gain of null ALS
mice was reduced by more than 30% relative to wild type mice, irrespective
of sex. Reductions in GH responsiveness were also seen for kidney
and linear growth. Absence of ALS eliminated the ability of GH to
increase plasma IGF-I despite intact GH-dependent stimulation of
IGF-I expression in liver, adipose tissue, and skeletal muscle. GH
treatment was also less efficient in antagonizing insulin action
in null ALS mice. Overall, these results suggest that the GH effects
mediated by endocrine IGF-I depends on ALS, and accordingly null
ALS mice are less responsive to exogenous GH therapy.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/7/3145}
}
@ARTICLE{Uemori2007,
author = {Uemori, Takashi and Mukai, Hiroyuki and Takeda, Osamu and Moriyama,
Mariko and Sato, Yoshimi and Hokazono, Shigekazu and Takatsu, Nariaki
and Asada, Kiyozo and Kato, Ikunoshin},
title = {Investigation of the Molecular Mechanism of ICAN, a Novel Gene Amplification
Method},
journal = {J. Biochem.},
year = {2007},
volume = {142},
pages = {283--292},
number = {2},
month = aug,
abstract = {Isothermal and Chimeric primer-initiated Amplification of Nucleic
acids (ICAN) allows the amplification of target DNA under isothermal
conditions at around 55{degrees}C using only a pair of 5'-DNA-RNA-3'
chimeric primers, thermostable RNaseH and a DNA polymerase with strand-displacing
activity (H. Mukai et al. J. Biochemistry, in the preceding paper
in this issue). Here we elucidated the mechanism of ICAN by analysing
the nicking site of RNaseH, behaviour of chimeric primers and extension
products. We found that the ICAN reaction was composed of two unique
mechanisms, multi-priming and template-switching, that were responsible
for the highly efficient amplifying capability of ICAN. The simultaneous
occurrence of two types of reactions, one based on multi-priming
and the other based on template-switching, is likely to drive the
DNA amplification in ICAN.},
url = {http://jb.oxfordjournals.org/cgi/content/abstract/142/2/283}
}
@ARTICLE{UEMURA2011,
author = {UEMURA, MAMORU and YAMAMOTO, HIROFUMI and TAKEMASA, ICHIRO and MIMORI,
KOSHI and MIZUSHIMA, TSUNEKAZU and IKEDA, MASATAKA and SEKIMOTO,
MITSUGU and DOKI, YUICHIRO and MORI, MASAKI},
title = {Hypoxia-inducible Adrenomedullin in Colorectal Cancer},
journal = {Anticancer Res},
year = {2011},
volume = {31},
pages = {507--514},
number = {2},
month = feb,
abstract = {Background: Recently, we determined several potential prognostic factors
in vivo using hypoxic tumor cells from hepatic metastases of colorectal
cancer (CRC). Among them, expression of adrenomedullin (ADM) was
an interesting target because it is highly induced by hypoxia. Patients
and Methods: To evaluate the prognostic impact of the expression
of ADM, samples from a total of 373 CRC patients were analyzed by
microarray (n=222), and quantitative reverse-transcriptase polymerase
chain reaction (n=151). Results: ADM was a novel independent prognostic
factor for CRC (p=0.027). ADM expression correlated with hypoxia-inducible
factor-1 A (p<0.0001) and vascular endothelial growth factor (p<0.0001)
in vivo. Conclusion: ADM expression is a useful marker for predicting
high risk of relapse and cancer-related death in patients who have
undergone curative resection for CRC.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/31/2/507}
}
@ARTICLE{Uemura2009,
author = {Uemura, Norihisa and Nakanishi, Yukihiro and Kato, Hoichi and Nagino,
Masato and Hirohashi, Setsuo and Kondo, Tadashi},
title = {Antibody-based proteomics for esophageal cancer: Identification of
proteins in the nuclear factor-κB pathway and mitotic checkpoint},
journal = {Cancer Science},
year = {2009},
volume = {100},
pages = {1612--1622},
number = {9},
abstract = {To identify the molecular background of esophageal cancer, we conducted
a proteomics study using an antibody microarray consisting of 725
antibodies and surgical specimens from three cases. The microarray
analysis identified 24 proteins with aberrant expression in esophageal
cancer compared with the corresponding normal mucosa. The overexpression
of 14 of the 24 proteins was validated by western blotting analysis
of the same samples. These 14 proteins were examined by immunohistochemistry,
in which nine proteins showed consistent results with those obtained
by western blotting. Among the nine proteins, seven were localized
in tumor cells, and two in infiltrating cells. The former included
proteins associated with mitotic checkpoint control and the nuclear
factor (NF)-κB pathway. Although mitotic checkpoint gene products
(budding uninhibited by benzidazoles 1 homolog beta (BubR1) and mitotic
arrest deficient-like 1 (Mad2)) have previously been reported to
be involved in esophageal cancer, the association of NF-κB-activating
kinase, caspase 10, and activator protein-1 with esophageal cancer
has not been previously reported. These proteins play a key role
in the NF-κB pathway, and NF-κB is a signal transduction factor
that has emerged as an important modulator of altered gene programs
and malignant phenotype in the development of cancer. The association
of these proteins with esophageal cancer may indicate that mitotic
checkpoint gene products and NF-κB play an important part in the
carcinogenesis of esophageal cancer. (Cancer Sci 2009; 100: 1612–1622)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2009.01230.x}
}
@ARTICLE{Ueno2003,
author = {Ueno, Yoshiyuki and Alpini, Gianfranco and Yahagi, Kaichiro and Kanno,
Noriatsu and Moritoki, Yuki and Fukushima, Koji and Glaser, Shannon
and LeSage, Gene and Shimosegawa, Tooru},
title = {Evaluation of differential gene expression by microarray analysis
in small and large cholangiocytes isolated from normal mice},
journal = {Liver International},
year = {2003},
volume = {23},
pages = {449--459},
number = {6},
abstract = {Abstract: Aims: We have shown that large and small cholangiocytes,
which reside primarily in large and small intrahepatic bile ducts,
respectively, have different functions and responses to injuries.
However, there are no systematic studies of the molecular differences
between small and large cholangiocytes, which would explain cholangiocyte
heterogeneity. To evaluate the differential gene expression between
small and large cholangiocytes, microarray analysis was performed.
Methods: Primary cultures of small and large cholangiocytes were
isolated from normal mice (BALB/c), and immortalized by the introduction
of the SV40 large T antigen gene. After cloning, small and large
cholangiocyte cell lines were established. Their characteristic features
were confirmed by electron microscopy (EM) and measurement of transepithelial
electrical resistance (TER), and secretin-stimulated cAMP levels.
Isolated total RNAs were hybridized with microarrays (Atlas Glass
Array Mouse 1.0 and 3.8), which detects 4850 cDNA expressions. After
hybridization, the fluorescent signals were scanned by a GenePix
fluorescent scanner and analyzed using ArrayGauge software. Results:
EM, TER and secretin-stimulated cAMP synthesis are consistent with
the concept that small and large immortalized cholangiocytes originate
from small and large ducts, respectively. When a cut-off value at
the expression signal difference of 3.0 times was employed, 230 cDNAs
among 4850 cDNAs (4.74%) were differentially expressed between small
and large cholangiocytes. Of these 230 cDNAs, aquaporin 8, IL-2 receptor
β chain and caspase 9 were more strongly expressed by large cholangiocytes.
Conclusions: Microarray successfully displayed characteristic differential
cDNA expression between small and large cholangiocytes. This technique
provides molecular information, which further supports our hypothesis
that small and large bile ducts have different functions.},
issn = {1478-3231},
keywords = {aquaporin, cholangiocytes, heterogeneity, immortalization, microarray},
publisher = {Munksgaard International Publishers},
url = {http://dx.doi.org/10.1111/j.1478-3231.2003.00876.x}
}
@ARTICLE{Ugaz2004,
author = {Ugaz, Victor M. and Elms, Rene D. and Lo, Roger C. and Shaikh, Faisal
A. and Burns, Mark A.},
title = {Microfabricated electrophoresis systems for DNA sequencing and genotyping
applications: current technology and future directions},
journal = {Phil Trans R Soc A},
year = {2004},
volume = {362},
pages = {1105--1129},
number = {1818},
month = may,
abstract = {Many routine genomic-analysis assays rely on gel electrophoresis to
perform size-selective fractionation of DNA fragments in the size
range below 1 kb in length. Over the past decade, impressive progress
has been made towards the development of microfabricated electrophoresis
systems to conduct these assays in a microfluidic lab-on-a-chip format.
Since these devices are inexpensive, require only nanolitre sample
volumes, and do not rely on the availability of a pre-existing laboratory
infrastructure, they are readily deployable in remote field locations
for use in a variety of medical and biosensing applications. The
design and construction of microfabricated electrophoresis devices
poses a variety of challenges, including the need to achieve high-resolution
separations over distances of a few centimetres or less, and the
need to easily interface with additional microfluidic components
to produce self-contained integrated DNA-analysis systems. In this
paper, we review recent efforts to develop devices to satisfy these
requirements and live up to the promise of fulfilling the growing
need for inexpensive portable genomic-analysis equipment.},
url = {http://rsta.royalsocietypublishing.org/cgi/content/abstract/362/1818/1105}
}
@ARTICLE{Uggla2005,
author = {Uggla, Bertil and Ståhl, Elisabet and Wågsäter, Dick and Paul, Christer
and Karlsson, Mats G. and Sirsjö, Allan and Tidefelt, Ulf},
title = {BCRP mRNA expression v. clinical outcome in 40 adult AML patients},
journal = {Leukemia Research},
year = {2005},
volume = {29},
pages = {141--146},
number = {2},
month = feb,
abstract = {Efflux pumps are considered being mechanisms behind drug resistance
in acute myeloid leukaemia (AML). A recently described efflux pump,
breast cancer resistance protein (BCRP), can be expressed in AML,
but its clinical importance is uncertain. In this study BCRP mRNA
expression was determined in samples from 40 AML patients by real-time
RT-PCR. The expression varied from negative to 76 times that of control
cells. There was no difference in BCRP mRNA expression between patients
responding to induction treatment and non-responders. However, in
the group of responders, the 14 patients with the highest expression
had significantly shorter overall survival (mean 38 months, SEM 15
months) than the 14 patients with the lowest (74 months, SEM 16 months)
(P = 0.047). This suggests a possible role of BCRP in drug resistance
in AML.},
issn = {0145-2126},
keywords = {Breast cancer resistance protein, Acute myeloid leukaemia, Drug resistance,
Prognosis, Reverse transcriptase polymerase chain reaction},
url = {http://www.sciencedirect.com/science/article/B6T98-4D1MYK1-1/2/7f6b9dd1b4944c20a534ac858be5b19b}
}
@ARTICLE{Ugocsai2010,
author = {Ugocsai, Peter and Hohenstatt, Antonia and Paragh, György and Liebisch,
Gerhard and Langmann, Thomas and Wolf, Zsuzsanna and Weiss, Thomas
and Groitl, Peter and Dobner, Thomas and Kasprzak, Piotr and Göbölös,
László and Falkert, Andreas and Seelbach-Goebel, Birgit and Gellhaus,
Alexandra and Winterhager, Elke and Schmidt, Markus and Semenza,
Gregg L. and Schmitz, Gerd},
title = {HIF-1beta determines ABCA1 expression under hypoxia in human macrophages},
journal = {The International Journal of Biochemistry \& Cell Biology},
year = {2010},
volume = {42},
pages = {241--252},
number = {2},
month = feb,
abstract = {ATP-binding cassette transporter A1 plays (ABCA1) a major role in
reverse cholesterol transport, a process closely related to atherogenesis.
In the thickening atherosclerotic lesions lipid loaded macrophages
are exposed to regions of local hypoxia that may influence reverse
cholesterol transport. Here we studied the effect of hypoxia on ABCA1
regulation and cholesterol efflux in human macrophages. We found
that the hypoxia-inducible factor 1 (HIF-1) specifically binds to
the HIF-1 response element of the ABCA1 promoter and the HIF-1 complex
increases ABCA1 promoter activity along with ABCA1 expression. Primary
human macrophages exposed to hypoxia or expressing constitutively
active HIF-1alpha responded with a potent change in ABCA1 expression,
which showed a strong correlation with HIF-1beta expression (r: 0.95-0.91).
Moreover, ABCA1-mediated cholesterol efflux was also found to be
regulated by HIF-1beta under hypoxia. In vivo, in macrophages prepared
from human atherosclerotic lesions ABCA1 levels showed a strong correlation
with HIF-1beta expression. This in vivo regulatory mechanism was
confirmed in human pre-eclamptic placentas, a clinical condition
with severe local hypoxia. These results demonstrate that HIF-1beta
availability determines ABCA1 expression and cholesterol efflux in
macrophages under hypoxia and may contribute to the interpersonal
variability of atherosclerotic lesion progression.},
issn = {1357-2725},
keywords = {ABCA1, Hypoxia, HIF-1, Macrophages, Atherosclerosis, Cholesterol efflux},
url = {http://www.sciencedirect.com/science/article/B6TCH-4XF8TN1-3/2/554dd7aacec6bf5824523b71749642fc}
}
@ARTICLE{Uhl2011,
author = {Uhl, Elizabeth and Krimer, Paula and Schliekelman, Paul and Tompkins,
S. Mark and Suter, Steven},
title = {Identification of altered MicroRNA expression in canine lymphoid
cell lines and cases of B- and T-Cell lymphomas},
journal = {Genes, Chromosomes and Cancer},
year = {2011},
volume = {50},
pages = {950--967},
number = {11},
abstract = {Canine lymphoma is a common spontaneous tumor with many similarities
to human lymphoma, and thus has potential to be an important animal
model of lymphomagenesis. This study determined that microRNA (miRNA)
expression in canine tumors can be assessed using a commercially
available human cancer miRNA qPCR array. miRNA expression in six
different canine lymphoid cell lines and in naturally occurring canine
B- and T-cell lymphomas was compared using RNA harvested from normal
canine peripheral blood mononuclear cells (PBMC) and normal lymph
nodes (LN) as controls. We found that false discovery rate (FDR)
correction for multiple testing after quantile normalization controlled
for variation across arrays and that they were the best methods for
normalization and statistical analysis. Increases in miRNAs known
to upregulate oncogenes (miR19a+b, miR17-5p) and decreased expression
of miRNAs with tumor suppressor functions (miR-203, miR-218, and
miR-181a) also seen in human lymphoid malignancies were observed.
However, there were few similarities between canine groups. The results
of this study indicate that the use of both PBMC and LN cells as
controls provides different, but potentially equally important targets
for further analysis. Our findings of miRNA dysregulation in canine
lymphoid cell lines and clinical cases of lymphoma emphasize the
potential of canine lymphoma as an important spontaneous, large animal
model of human B- and T-cell lymphomas. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/gcc.20917},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20917}
}
@ARTICLE{Uhrig2008,
author = {Uhrig, Markus and Brechlin, Peter and Jahn, Olaf and Knyazev, Yuri
and Weninger, Annette and Busia, Laura and Honarnejad, Kamran and
Otto, Markus and Hartmann, Tobias},
title = {Upregulation of CRABP1 in human neuroblastoma cells overproducing
the Alzheimer-typical Aß42 reduces their differentiation potential},
journal = {BMC Medicine},
year = {2008},
volume = {6},
pages = {38},
number = {1},
abstract = {BACKGROUND:Alzheimer's disease (AD) is characterized by neurodegeneration
and changes in cellular processes, including neurogenesis. Proteolytic
processing of the amyloid precursor protein (APP) plays a central
role in AD. Owing to varying APP processing, several ß-amyloid peptides
(Aß) are generated. In contrast to the form with 40 amino acids (Aß40),
the variant with 42 amino acids (Aß42) is thought to be the pathogenic
form triggering the pathological cascade in AD. While total-Aß effects
have been studied extensively, little is known about specific genome-wide
effects triggered by Aß42 or Aß40 derived from their direct precursor
C99.METHODS:A combined transcriptomics/proteomics analysis was performed
to measure the effects of intracellularly generated Aß peptides in
human neuroblastoma cells. Data was validated by real-time polymerase
chain reaction (real-time PCR) and a functional validation was carried
out using RNA interference.RESULTS:Here we studied the transcriptomic
and proteomic responses to increased or decreased Aß42 and Aß40 levels
generated in human neuroblastoma cells. Genome-wide expression profiles
(Affymetrix) and proteomic approaches were combined to analyze the
cellular response to the changed Aß42- and Aß40-levels. The cells
responded to this challenge with significant changes in their expression
pattern. We identified several dysregulated genes and proteins, but
only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated
exclusively in cells expressing an increased Aß42/Aß40 ratio. This
consequently reduced all-trans retinoic acid (RA)-induced differentiation,
validated by CRABP1 knock down, which led to recovery of the cellular
response to RA treatment and cellular sprouting under physiological
RA concentrations. Importantly, this effect was specific to the AD
typical increase in the Aß42/Aß40 ratio, whereas a decreased ratio
did not result in up-regulation of CRABP1.CONCLUSION:We conclude
that increasing the Aß42/Aß40 ratio up-regulates CRABP1, which in
turn reduces the differentiation potential of the human neuroblastoma
cell line SH-SY5Y, but increases cell proliferation. This work might
contribute to the better understanding of AD neurogenesis, currently
a controversial topic.},
doi = {10.1186/1741-7015-6-38},
issn = {1741-7015},
pubmedid = {19087254},
url = {http://www.biomedcentral.com/1741-7015/6/38}
}
@ARTICLE{Uittenbogaard2010,
author = {Uittenbogaard, Martine and Baxter, Kristin K. and Chiaramello, Anne},
title = {NeuroD6 genomic signature bridging neuronal differentiation to survival
via the molecular chaperone network},
journal = {J. Neurosci. Res.},
year = {2010},
volume = {88},
pages = {33--54},
number = {1},
abstract = {Abstract 10.1002/jnr.22182.abs During neurogenesis, expression of
the basic helix-loop-helix NeuroD6/Nex1/MATH-2 transcription factor
parallels neuronal differentiation and is maintained in differentiated
neurons in the adult brain. To dissect NeuroD6 differentiation properties
further, we previously generated a NeuroD6-overexpressing stable
PC12 cell line, PC12-ND6, which displays a neuronal phenotype characterized
by spontaneous neuritogenesis, accelerated NGF-induced differentiation,
and increased regenerative capacity. Furthermore, we reported that
NeuroD6 promotes long-term neuronal survival upon serum deprivation.
In this study, we identified the NeuroD6-mediated transcriptional
regulatory pathways linking neuronal differentiation to survival,
by conducting a genome-wide microarray analysis using PC12-ND6 cells
and serum deprivation as a stress paradigm. Through a series of filtering
steps and a gene-ontology analysis, we found that NeuroD6 promotes
distinct but overlapping gene networks, consistent with the differentiation,
regeneration, and survival properties of PC12-ND6 cells. By using
a gene-set-enrichment analysis, we provide the first evidence of
a compelling link between NeuroD6 and a set of heat shock proteins
in the absence of stress, which may be instrumental in conferring
stress tolerance on PC12-ND6 cells. Immunocytochemistry results showed
that HSP27 and HSP70 interact with cytoskeletal elements, consistent
with their roles in neuritogenesis and preserving cellular integrity.
HSP70 also colocalizes with mitochondria located in the soma, growing
neurites, and growth cones of PC12-ND6 cells prior to and upon stress
stimulus, consistent with its neuroprotective functions. Collectively,
our findings support the notion that NeuroD6 links neuronal differentiation
to survival via the network of molecular chaperones and endows the
cells with increased stress tolerance. © 2009 Wiley-Liss, Inc.},
issn = {1097-4547},
keywords = {heat shock proteins, heat shock transcription factors, NeuroD family,
basic helix-loop-helix transcription factors, stress tolerance},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.22182}
}
@ARTICLE{Ukena2011,
author = {Ukena, Sya N. and Velaga, Sarvari and Geffers, Robert and Grosse,
Jens and Baron, Udo and Buchholz, Stefanie and Stadler, Michael and
Bruder, Dunja and Ganser, Arnold and Franzke, Anke},
title = {Human regulatory T cells in allogeneic stem cell transplantation},
journal = {Blood},
year = {2011},
volume = {118},
pages = {e82-92},
number = {13},
abstract = {GVHD is still one of the major complications after allogeneic stem
cell transplantation. Whereas murine data have clearly shown the
beneficial effects of regulatory T cells (Tregs) on the prevention
of GVHD, data from the human system are rare. Here, we present a
comparative dynamic analysis of CD4+CD25hiCD127lo/- Tregs from patients
with and without GVHD analyzing the whole genome profile over the
first 6 months after stem cell transplantation, representing the
most sensitive time window for tolerance induction. The Treg transcriptome
showed a high stability. However, the comparison of Treg transcriptomes
from patients with and without GVHD uncovered regulated gene transcripts
highly relevant for Treg cell function. The confirmative protein
analyses demonstrated a significantly higher expression of granzyme
A, CXCR3, and CCR5 in Tregs of immune tolerant patients. These results
point to a reduced suppressive function of Tregs from GVHD patients
with diminished migration capacity to the target organs.},
doi = {10.1182/blood-2011-05-352708},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/13/e82.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/13/e82}
}
@ARTICLE{Ukropec2006,
author = {Ukropec, Jozef and Anunciado, Rea P. and Ravussin, Yann and Hulver,
Matthew W. and Kozak, Leslie P.},
title = {UCP1-independent Thermogenesis in White Adipose Tissue of Cold-acclimated
Ucp1-/- Mice},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {31894--31908},
number = {42},
month = oct,
abstract = {Apart from UCP1-based nonshivering thermogenesis in brown adipocytes,
the identity of thermogenic mechanisms that can be activated to reduce
a positive energy balance is largely unknown. To identify potentially
useful mechanisms, we have analyzed physiological and molecular mechanisms
that enable mice, genetically deficient in UCP1 and sensitive to
acute exposure to the cold at 4 {degrees}C, to adapt to long term
exposure at 4 {degrees}C. UCP1-deficient mice that can adapt to the
cold have increased oxygen consumption and show increased oxidation
of both fat and glucose as indicated from serum metabolite levels
and liver glycogen content. Enhanced energy metabolism in inguinal
fat was also indicated by increased oxygen consumption and fat oxidation
in tissue suspensions and increased AMP kinase activity in dissected
tissues. Analysis of gene expression in skeletal muscle showed surprisingly
little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas
in inguinal fat a robust induction occurred for type 2 deiodinase,
sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate
dehydrogenase, PGC1{alpha}, CoxII, and mitochondrial DNA content.
Western blot analysis showed an induction of total phospholamban
and its phosphorylated form in inguinal fat and other white fat depots,
but no induction was apparent in muscle. We conclude that alternative
thermogenic mechanisms, based in part upon the enhanced capacity
for ion and substrate cycling associated with brown adipocytes in
white fat depots, are induced in UCP1-deficient mice by gradual cold
adaptation.},
url = {http://www.jbc.org/cgi/content/abstract/281/42/31894}
}
@ARTICLE{Ukropec2006a,
author = {Ukropec, Jozef and Anunciado, Rea V. P. and Ravussin, Yann and Kozak,
Leslie P.},
title = {Leptin Is Required for Uncoupling Protein-1-Independent Thermogenesis
during Cold Stress},
journal = {Endocrinology},
year = {2006},
volume = {147},
pages = {2468--2480},
number = {5},
month = may,
abstract = {We investigated the role of leptin in regulating energy metabolism
through induction of uncoupling protein (UCP)-1-based brown fat thermogenesis
by comparing phenotypes of energy balance in ob/ob and double-mutant
ob/ob.Ucp1-/- mice. Measurements of adiposity and lean body mass
(nuclear magnetic resonance), energy expenditure (indirect calorimetry),
body weight, food intake, and core body temperature were determined
in the two mutant stocks of 3-month-old mice maintained at an initial
ambient temperature of 28 C for 21 d and then at 21 C for 16 d, and
finally with leptin administration for 8 d at 21 C. No phenotypic
differences between ob/ob and ob/ob.Ucp1-/- mice were detected, suggesting
that UCP1-based thermogenesis is not essential for the regulation
of adiposity in ob/ob mice at temperatures between 21 and 28 C. Although
both Ucp1-/- and ob/ob mice can survive in extreme cold at 4 C, provided
they are adapted to the cold by gradually lowering ambient temperature,
ob/ob.Ucp1-/- mice could not adapt and survive at temperatures lower
than 12 C unless they were administered leptin. As the ambient temperature
was reduced from 20 to 16 C, ob/ob.Ucp1-/- mice treated with leptin
have elevated levels of circulating T3 that correlate with elevated
sarcoendoplasmic reticulum Ca2+ ATPase 2a mRNA levels in gastrocnemius
muscle. Furthermore, ob/ob.Ucp1-/- mice, treated with T3, were able
to maintain body temperature and stimulate sarcoendoplasmic reticulum
Ca2+ ATPase 2a expression when the ambient temperature was gradually
reduced to 4 C. Thus, in the absence of UCP1, leptin-induced thermogenesis
protects body temperature in part through its action on the thyroid
hormone axis.},
url = {http://endo.endojournals.org/cgi/content/abstract/147/5/2468}
}
@ARTICLE{Ulbrich2011,
author = {Ulbrich, Susanne E. and Meyer, Swanhild U. and Zitta, Karina and
Hiendleder, Stefan and Sinowatz, Fred and Bauersachs, Stefan and
Büttner, Mathias and Fröhlich, Thomas and Arnold, Georg J. and Reichenbach,
Horst-Dieter and Wolf, Eckhard and Meyer, Heinrich H.D.},
title = {Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase
inhibitor TIMP2 participate in maternal preparation of pregnancy},
journal = {Molecular and Cellular Endocrinology},
year = {2011},
volume = {332},
pages = {48--57},
number = {1-2},
month = jan,
abstract = {Early embryonic development is critically dependent on both maternal
preparation and embryonic signalling of pregnancy. Matrix metallopeptidases
(MMP) contribute to spatial and temporal matrix remodeling in the
bovine endometrium. In this study we observed distinct changes in
expression of MMP2, MMP14, and the metallopeptidase inhibitor TIMP2
between different phases of the estrous cycle indicating an endocrine
regulation. An increase of TIMP2 protein abundance was ascertained
in the uterine lumen during the time of embryo elongation. The expression
pattern and cellular localization correlate well with the assumed
effects of MMPs on release and activation of cytokines and growth
factors directing cell migration, differentiation, and vascularization
during this pivotal period of development. Specifically, active MMP2
in the endometrium may determine the allocation of growth factors
supporting conceptus development. The presence of a day 18 conceptus
in vivo and day 8 blastoysts in vitro induced endometrial TIMP2 mRNA
expression. The results imply that TIMP2 is involved in very early
local maternal recognition of pregnancy. Matrix metallopeptidases
are likely to participate in remodeling processes preparing a receptive
endometrium for a timely and precise regulation of embryo development.},
issn = {0303-7207},
keywords = {Matrix metallopeptidases, Metallopeptidase inhibitor, Preimplantation,
Pregnancy, Bos taurus, Endometrium},
url = {http://www.sciencedirect.com/science/article/pii/S0303720710004703}
}
@ARTICLE{Ulbrich2009,
author = {Ulbrich, S E and Schulke, K and Groebner, A E and Reichenbach, H
D and Angioni, C and Geisslinger, G and Meyer, H H D},
title = {Quantitative characterization of prostaglandins in the uterus of
early pregnant cattle},
journal = {Reproduction},
year = {2009},
volume = {138},
pages = {371--382},
number = {2},
month = aug,
abstract = {Prostaglandins (PGs) are important regulators of reproductive processes
including early embryonic development. We analyzed the most relevant
PG in bovine uteri at different preimplantation pregnancy stages
when compared with non-pregnant controls. Additionally, endometrium
and trophoblast tissues were examined regarding specific enzymes
and receptors involved in PG generation and function. Simmental heifers
were artificially inseminated or received seminal plasma only. At
days 12, 15, or 18, post-estrus uteri were flushed for PG determination
by liquid chromatography-tandem mass spectrometry. Endometrium and
trophoblast tissues were sampled for RNA extraction and quantitative
real-time PCR analysis. At all days and points of time examined,
the concentration of 6-keto PGF1{alpha} (stable metabolite of PGI2)
was predominant followed by PGF2{alpha}>PGE2>PGD2{approx}TXB2 (stable
metabolite of TXA2). At days 15 and 18, PG increased from overall
low levels at day 12, with a much more pronounced increase during
pregnancy. The PGF2{alpha}/PGE2 ratio was not influenced by status.
The highest PG concentration was measured at day 15 with 6-keto PGF1{alpha}
(6.4 ng/ml) followed by PGF2{alpha} (1.1 ng/ml) and PGE2 (0.3 ng/ml).
Minor changes in endometrial PG biosynthesis enzymes occurred due
to pregnancy. Trophoblasts revealed high transcript abundance of
general and specific PG synthases contributing to uterine PG. As
PGI2 and PGF2{alpha} receptors were abundantly expressed by the trophoblast,
abundant amounts of PGI2 and PGF2{alpha} in the uterine lumen point
towards an essential role of PG for the developing embryo. High amounts
of PG other than PGE2 in the preimplantation uterus may be essential
rather than detrimental for successful reproduction.},
url = {http://www.reproduction-online.org/cgi/content/abstract/138/2/371}
}
@ARTICLE{Ulrich2010,
author = {Ulrich, Reiner and Kalkuhl, Arno and Deschl, Ulrich and Baumgärtner,
Wolfgang},
title = {Machine learning approach identifies new pathways associated with
demyelination in a viral model of multiple sclerosis},
journal = {Journal of Cellular and Molecular Medicine},
year = {2010},
volume = {14},
pages = {434--448},
number = {1-2},
abstract = {Abstract Theiler’s murine encephalomyelitis is an experimentally
virus-induced inflammatory demyelinating disease of the spinal cord,
displaying clinical and pathological similarities to chronic progressive
multiple sclerosis. The aim of this study was to identify pathways
associated with chronic demyelination using an assumption-free combined
microarray and immunohistology approach. Movement control as determined
by rotarod assay significantly worsened in Theiler’s murine encephalomyelitis
-virus-infected SJL/J mice from 42 to 196 days after infection (dpi).
In the spinal cords, inflammatory changes were detected 14 to 196
dpi, and demyelination progressively increased from 42 to 196 dpi.
Microarray analysis revealed 1001 differentially expressed genes
over the study period. The dominating changes as revealed by k-means
and functional annotation clustering included up-regulations related
to intrathecal antibody production and antigen processing and presentation
via major histocompatibility class II molecules. A random forest
machine learning algorithm revealed that down-regulated lipid and
cholesterol biosynthesis, differentially expressed neurite morphogenesis
and up-regulated toll-like receptor-4-induced pathways were intimately
associated with demyelination as measured by immunohistology. Conclusively,
although transcriptional changes were dominated by the adaptive immune
response, the main pathways associated with demyelination included
up-regulation of toll-like receptor 4 and down-regulation of cholesterol
biosynthesis. Cholesterol biosynthesis is a rate limiting step of
myelination and its down-regulation is suggested to be involved in
chronic demyelination by an inhibition of remyelination.},
issn = {1582-4934},
keywords = {cholesterol, demyelination, immunohistology, microarray, multiple
sclerosis, random forest machine learning algorithm, spinal cord,
Theiler’s murine encephalomyelitis, toll-like receptor 4},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2008.00646.x}
}
@ARTICLE{Ulrich2010a,
author = {Ulrich, Robert M. and Casper, Erica T. and Campbell, Lisa and Richardson,
Bill and Heil, Cynthia A. and Paul, John H.},
title = {Detection and quantification of Karenia mikimotoi using real-time
nucleic acid sequence-based amplification with internal control RNA
(IC-NASBA)},
journal = {Harmful Algae},
year = {2010},
volume = {9},
pages = {116--122},
number = {1},
month = jan,
abstract = {Nucleic acid sequence-based amplification (NASBA) is an isothermal
method used to amplify RNA and has been used for clinical, environmental,
and food testing applications. Quantification of RNA by real-time
NASBA occurs by comparing time to positive (TTP) fluorescence values,
similar to threshold cycle (Ct) values in PCR, of unknown samples
to a standard curve of known RNA titers. Incorporation of an internal
control RNA molecule (IC-RNA) has been used to increase precision
and accuracy of real-time NASBA and also serves as an indicator of
NASBA inhibition. A real-time IC-NASBA assay was developed targeting
the ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) large-subunit
gene (rbcL) of the harmful algal bloom (HAB) causing dinoflagellate
Karenia mikimotoi. This assay is sensitive to one K. mikimotoi cell
and 1 × 103 copies of in vitro transcript with a high degree of specificity
against closely related organisms. Enumeration of K. mikimotoi from
environmental samples by IC-NASBA was not significantly different
from microscopic cell counts (P = 0.156, [alpha] = 0.05) performed
by the Fish and Wildlife Research Institute (FWRI, a division of
the Fish and Wildlife Conservation Commission, St. Petersburg, FL),
the agency responsible for monitoring red tide status throughout
the state. In addition, the IC-NASBA enumeration had a good linear
relationship (r2 = 0.887) with FWRI microscopic cell counts. IC-NASBA
is an alternative method for the rapid and reliable detection and
quantification of K. mikimotoi from marine waters.},
issn = {1568-9883},
keywords = {IC-NASBA, Internal control RNA, Karenia brevis, Quantitative NASBA},
url = {http://www.sciencedirect.com/science/article/B73D7-4X49YGK-1/2/83c0d52f271a958ca7da5f2d378496c4}
}
@ARTICLE{Ulrich-Merzenich2011,
author = {Ulrich-Merzenich, G. and Koptina, A. and Kelber, O. and Freischmidt,
A. and Heilmann, J. and Müller, J. and Sadeghlar, F. and Zeitler,
H. and Wagner, H.},
title = {Prediction of adverse events by in vivo gene expression profiling
exemplified for phytopharmaceuticals containing salicylates and the
antidepressant imipramine},
journal = {Phytomedicine},
year = {2011},
pages = {--},
month = nov,
abstract = {Gene expression profiles of Sprague-Dawley (SD) rats treated with
a standardized willow bark extract (WB), its salicin rich ethanol
fraction (EtOH-FR) or the tricyclic antidepressant imipramine were
evaluated for their potential to induce adverse events. Treatments
had shown antidepressant-like effects. Gene expression profiles (Agilent
Whole Genome Array, n=4/group) obtained from the peripheral blood
of male SD rats treated with WB (STW 33-I), EtOH-FR (30mg/kg bw)
or imipramine (20mg/kg bw) were analysed comparatively by the Ingenuity
Systems Programme, which allows to conduct model calculations of
thresholds for theoretical potential adverse events (AE). The number
of genes regulated by the three treatments were 1673 (WB), 117 (EtOH-FR)
and 1733 (imipramine). The three treatments related to 47 disease
clusters. The WB extract reached the threshold for a potential AE
in one disease cluster (cardiac hypertrophy), whereas the EtOH-FR
exceeded the threshold in 5 disease clusters (cardiac arteriopathy
and stenosis, glomerular injury, pulmonary hypertension, alkaline
phosphatase levels ⇑). Imipramine treatment hit 13 disease clusters:
tachycardia, palpitation, myocardial infarction, arrhythmias, heart
block, precipitation of congestive heart failure; urinary retention,
altered liver functions. Those correspond to known potential adverse
events. Glomerular injury and altered liver functions are part of
the side effect profile of salicylic acid derivatives in agreement
with the findings for the salicin rich EtOH-FR. There is no linear
relationship between the number of constituents of a drug (preparation)
and the number of different targets hit in a biological system on
the gene expression level. Therefore, the number of genetic targets
in a biological system does not necessarily increase with the complexity
of the treatment corresponding to the non-linear behaviour of biological
systems. Regarding gene expression levels AE of single treatments
are not necessarily additive in combination treatments. The applied
method appears to be an interesting screening tool for the prediction
of potential AE. The phenomena that imipramine crossed the potential
threshold for AEs several times whereas the WB extract did reach
the threshold level only once, however not backed by clinical data
for this AE, deserves to be further investigated. It questions the
commonly assumed principle that substances with low number or without
AE will have a poor efficacy.},
issn = {0944-7113},
keywords = {4EBP1, eukaryotic translation initiation factor 4E binding protein
1, ADRA1D, adrenergic α-1D-receptor, AE, adverse events, ACE, angiotensin
I converting enzyme (peptidyl-dipeptidase A) 1, SD, Sprague-Dawley,
DAG, diacylglycerol, DMARD, disease modifying anti-rheumatic drug,
ECM, extra cellular matrix, EDNRA, endothelin receptor, eIF4s, mRNA
binding translation factors, EPO, erythropoietin, ER, estrogen receptor,
EtOH-FR, ethanol fraction, FES, Agilent Feature Extraction software,
FST, Porsolt Swimming Test, G protein, guanine-nucleotide-binding
protein, HIF, hypoxia inducible factor-1, IP3, phosphatidyl-inositol-1,4,5
triphosphate, IPA, Ingenuity Pathways Analysis, JNK, c-Jun N-terminal
kinase, MS, multiple sclerosis, MTX, methotrexate, NOS1, nitric oxide
synthase 1, PAD, peripheral arterial disease, PDGF, platelet-derived
growth factor beta, RXR, retinoid x receptor, TIMP3, tissue inhibitor
of metalloproteinase 3, VDR, vitamin D (1,25-dihydroxyvitamin D3)
receptor, VEGF, vascular endothelial growth factor, WB, willow bark
extract, Adverse events, Antidepressant, Multitarget, Salicylates
(Salicin), Imipramine, Gene microarray},
publisher = {Urban \& Fischer Verlag},
refid = {S0944-7113(11)00486-7},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0944711311004867?showall=true}
}
@ARTICLE{Ulve2008,
author = {Ulve, V.M. and Monnet, C. and Valence, F. and Fauquant, J. and Falentin,
H. and Lortal, S.},
title = {RNA extraction from cheese for analysis of in situ gene expression
of Lactococcus lactis},
journal = {Journal of Applied Microbiology},
year = {2008},
volume = {105},
pages = {1327--1333},
number = {5},
abstract = {Abstract Aims:  The isolation of high-quality RNA from cheese is
a prerequisite for analysis of in situ gene expression of dairy micro-organisms.
Methods and Results:  A method for rapid isolation of bacterial
cells from cheese using cold citrate buffer followed by mechanical
cell disruption was developed. RNA was extracted from experimental
ultrafiltration (UF) cheeses (at 2, 8, 24Â h, 7 and 14 days) and
from Cheddar cheese (from 1 day to 1 year). The quantity and quality
of the extracted RNA was assessed. The transcript abundance of seven
genes (tuf, gapB, purM, cysK, ldh, cit and gyrA) was estimated by
reverse transcription real-time PCR. In UF cheeses, the quantity
of RNA extracted increased from 0·2 to 24 μg g−1, with an RNA
Integrity Number (RIN) above 9. In the experimental Cheddar cheeses,
the RNA extraction yield decreased from 67·7 μg g−1 after 1
day to 23·7 μg g−1 after 6 months, with RIN value above 9 during
the first month. The transcript abundance of the seven genes demonstrated
metabolic activity of lactococci after several weeks of ripening
in both cheeses. Significance and Impact of the Study:  The method
described produced large quantities of high-quality RNA for future
whole genome expression studies in cheese.},
issn = {1365-2672},
keywords = {cheese, Lactococcus lactis, real-time PCR, RNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2672.2008.03869.x}
}
@ARTICLE{Umemoto2009,
author = {Umemoto, Yoshihiro and Kataoka, Masatoshi and Yatsushiro, Shouki
and Watanabe, Masahiro and Kido, Jun-ichi and Kakuhata, Rei and Yamamoto,
Takenori and Shinohara, Yasuo and Baba, Yoshinobu},
title = {Sequential analysis of RNA synthesis by microchip electrophoresis},
journal = {Analytical Biochemistry},
year = {2009},
volume = {388},
pages = {161--163},
number = {1},
month = may,
abstract = {We describe the potential of microchip electrophoresis with a Hitachi
SV1100, which can be used to evaluate the integrity of total RNA,
for the analysis of synthesized RNA. There was little interference
by DNA and/or the components of the in vitro transcription system
with the microchip electrophoresis. The fluorescence intensity corresponding
to the synthesized RNA increased in a time-dependent manner as to
the RNA synthesis reaction on sequential analysis. A result can be
obtained in 160 s and only 1/10 aliquots of samples, compared with
the conventional method, are required. These results indicate the
potential of microchip electrophoresis for sequential analysis of
RNA synthesis.},
issn = {0003-2697},
url = {http://www.sciencedirect.com/science/article/B6W9V-4VHSDJH-7/2/b0764420cfb0d573a4a23dc3bac3236b}
}
@ARTICLE{Umemoto2010,
author = {Umemoto, Y. and Kataoka, M. and Yatsushiro, S. and Yamamura, S. and
Ooie, T. and Kido, J. and Yamamoto, T. and Shinohara, Y., Baba, Y.},
title = {Analysis of DNA ligation by microchip electrophoresis},
journal = {Journal of Pharmaceutical and Biomedical Analysis},
year = {2010},
volume = {52},
pages = {323--328},
number = {2},
month = jun,
abstract = {We describe the potential of microchip electrophoresis with a Hitachi
SV1100, which can be used to determine DNA sizes between 500 and
5000 bp with good quantification (DNA concentration, <8 ng/l) within
5 min, for the analysis of DNA ligation. On analysis of an electropherogram
of a ligation mixture of the pTAC1-T vector and a 789 bp PCR-amplified
DNA fragment, the presence of recombinant DNA was easily detected
by comparison with an electropherogram obtained without ligase. On
analysis of a ligation mixture of pUC19/Eco RI without alkaline phosphatase
treatment and a 667 bp Eco RI-digested fragment of foreign DNA, several
peaks observed in the electropherogram corresponded to the formation
of monomeric and polymeric insert DNAs, self-ligated vector DNA,
and recombinant DNA. On the other hand, several peaks were also observed
in the electropherogram of the ligation mixture of pUC19/Eco RI with
alkaline phosphatase treatment and the 667 bp Eco RI-digested fragment
of foreign DNA, the fluorescence intensity corresponding to recombinant
DNA apparently being increased. These results indicate the potential
of microchip electrophoresis for the analysis of DNA ligation, it
offering high resolution in a short time.},
issn = {0731-7085},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20196235}
}
@ARTICLE{Umland2003,
author = {Umland, Shelby P. and Garlisi, Charles G. and Shah, Himanshu and
Wan, Yuntao and Zou, Jun and Devito, Kristine E. and Huang, Whei-Mei
and Gustafson, Eric L. and Ralston, Robert},
title = {Human ADAM33 Messenger RNA Expression Profile and Post-Transcriptional
Regulation},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2003},
volume = {29},
pages = {571--582},
number = {5},
month = nov,
abstract = {We examined transcript expression and post-transcriptional regulation
of human ADAM33, a recently identified asthma gene. A detailed messenger
RNA (mRNA) expression profile was obtained using Northern, reverse
transcription polymerase chain reaction, and in situ hybridization
analyses. ADAM33 mRNA was expressed significantly in smooth muscle-containing
organs, minimally in immune organs and hematopoietic cells, and highly
in repairing duodenal granulation tissue. Expression was seen in
asthmatic subepithelial fibroblasts and smooth muscle but not in
respiratory epithelium. In all tissues, transcripts of [~] 5 kb predominated
over those of [~] 3.5 kb by 2- to 5-fold. The effect of the 3' untranslated
region (UTR) on ADAM33 protein expression and maturation was examined.
The presence of the 3'UTR in untagged full-length constructs promoted
prodomain removal, detected as mature [~] 100 kD protein by ADAM33-reactive
antibodies; in its absence, maturation was 2- to 3-fold less in HEK293
cells. His-tagged and untagged constructs lacking the 3'UTR demonstrated
that lack of maturation was not a result of tag-mediated effects.
Minimal maturation of ADAM33 occurred in primary lung and MRC5 fibroblasts
following adenoviral-mediated expression of ADAM33 lacking the 3'UTR.
In contrast, prodomain removal was observed with plasmids and adenovirus
encoding only the pro- and catalytic domains. Thus, the 3'UTR of
ADAM33 and domains downstream of the catalytic domain regulate potential
ADAM33 activity. Mechanisms of regulation of ADAM33, distinct from
closely related ADAMs, thus include mRNA localization and processing
and protein maturation.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/29/5/571}
}
@ARTICLE{Umland2004,
author = {Umland, Shelby P. and Wan, Yuntao and Shah, Himanshu and Garlisi,
Charles G. and Devito, Kristine E. and Braunschweiger, Karen and
Gheyas, Ferdous and Del Mastro, Richard},
title = {Mouse ADAM33: Two Splice Variants Differ in Protein Maturation and
Localization},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2004},
volume = {30},
pages = {530--539},
number = {4},
month = apr,
abstract = {We compared the tissue mRNA prevalence and protein maturation of two
splice variants of mouse ADAM33, a metalloprotease implicated in
airway hyperresponsiveness. These variant cDNAs, designated 914 ({alpha})
and 906 ({beta}), encode membrane-bound forms that differ primarily
in 26 residues (exon 17) between the cysteine-rich and epidermal
growth factor-like domains. Proteins of [~] 120 and 103 kD, detectable
by anti-ADAM33 antibodies, were expressed in 914-transfected HEK293
cells. The time-dependent appearance of the [~] 100-kD form and its
inhibition by a peptidyl chloromethylketone, or the calcium ionophore,
A23187, indicated that this was mature ADAM33, which was processed
by a furin-like convertase. One form, [~] 110 kD, was detected in
906-transfected cell lysates. Trypsin and biotinylation treatment
of transfected cells demonstrated that all of the mature [~] 100-kD,
a minority of the [~] 120-kD pro-form, and none of the 906-expressed
110-kD form localized to the cell surface. The mature form was resistant
to endoglycosidase Hf. The [~] 110-kD form was endoglycosidase Hf-sensitive,
indicating retention proximal to the trans-Golgi, consistent with
a lack of maturation. Quantitation of transcripts demonstrated that
those containing exon 17 predominate, whereas those lacking exon
17 are negligible in the mouse lung, although detectable at low levels
in mouse testis, heart, and brain. Thus, potential dominant-negative
effects exerted by the nonprocessed 906-encoded {beta} splice variant
are unlikely to occur in mouse lung.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/30/4/530}
}
@ARTICLE{Unal2010,
author = {Unal, Resat and Yao-Borengasser, Aiwei and Varma, Vijayalakshmi and
Rasouli, Neda and Labbate, Craig and Kern, Philip A. and Ranganathan,
Gouri},
title = {Matrix Metalloproteinase-9 Is Increased in Obese Subjects and Decreases
in Response to Pioglitazone},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {2993--3001},
number = {6},
month = jun,
abstract = {Context: The study investigated the regulation of matrix metalloproteinases
(MMP)-9 in obesity-associated insulin resistance in humans. Objectives:
The objectives of the investigation were to study MMP-9 regulation
by insulin resistance and pioglitazone treatment in impaired glucose
tolerant subjects using adipose tissue biopsies and study the mechanism
of MMP-9 regulation by pioglitazone in adipocyte cultures. Research
Design: 86 nondiabetic, weight-stable subjects between 21 and 66
yr of age were recruited in a university hospital research center
setting. All subjects underwent a sc adipose tissue incisional biopsy
from the lower abdominal wall and insulin sensitivity testing using
a frequently sampled iv glucose tolerance test. Impaired glucose-tolerant
subjects were randomized to receive metformin or pioglitazone for
10 wk. To study the mechanism of MMP-9 regulation in adipocytes,
cells were treated with pioglitazone or protein kinase C{alpha} antisense
oligomers, and MMP-9 levels were examined. Results: There was a positive
correlation between MMP-9 and body mass index (r = 0.40, P < 0.01)
and negative correlation between MMP-9 and insulin sensitivity (r
= -0.46, P < 0.001). The improvement in insulin sensitivity from
pioglitazone resulted in a 52 {+/-} 0.2% reduction in MMP-9 mRNA.
Fractionation of adipose tissue indicated that MMP-9 was mostly in
the stromal vascular fraction. Pioglitazone also decreased MMP-9
in 3T3-F442A adipocytes and THP1 macrophages. Coculture of adipocytes
with macrophages augmented MMP-9 expression in adipocytes and pioglitazone
decreased MMP-9 in both adipocytes and macrophages. Conclusion: These
data indicate that MMP-9 is elevated in insulin resistance and is
reduced by pioglitazone.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/6/2993}
}
@ARTICLE{Undale2010,
author = {Undale, Anita and Srinivasan, Bhuma and Drake, Matthew and McCready,
Louise and Atkinson, Elizabeth and Peterson, James and Riggs, B.
Lawrence and Amin, Shreyasee and Moedder, U.I. and Khosla, Sundeep},
title = {Circulating osteogenic cells: Characterization and relationship to
rates of bone loss in postmenopausal women},
journal = {Bone},
year = {2010},
volume = {47},
pages = {83--92},
number = {1},
month = jul,
abstract = {There is increasing evidence that osteogenic cells are present not
only in bone marrow (BM) but also in peripheral blood (PB). Since
staining for alkaline phosphatase (AP) identifies osteoprogenitor
cells in BM, we sought to further characterize BM versus PB hematopoietic
lineage negative (lin−)/AP+ cells and to compare gene expression
in PB lin−/AP+ cells from postmenopausal women undergoing rapid
versus slow bone loss. PB lin−/AP+ cells were smaller than their
BM counterparts, and both were negative for the pan-hematopoietic
marker, CD45. BM and PB lin−/AP+ cells were capable of mineralization
in vitro. Using whole genome linear amplification followed by quantitative
polymerase chain reaction (QPCR) analysis, we found that relative
to the BM cells, PB lin−/AP+ cells expressed similar levels of
a number of key osteoblast marker genes (runx2, osterix, osteopontin,
OPG, periostin), consistent with the PB cells being in the osteoblastic
lineage. Importantly, however, compared to the BM cells, PB lin−/AP+
cells expressed lower levels of mRNAs for AP, type I collagen, and
for a panel of proliferation markers, but higher levels of osteocalcin,
osteonectin, and PTHR1 mRNAs, as well as those for RANKL and ICAM-1,
both of which are important in supporting osteoclastogenesis. Using
microarray followed by QPCR analysis, we further demonstrated that,
compared to postmenopausal women undergoing slow bone loss, PB lin−/AP+
cells from women undergoing rapid bone loss expressed lower levels
of mRNAs for hydroxyprostaglandin dehydrogenase, interferon regulator
factor 3, Wnt1-induced secreted protein 1, and TGFβ2, but higher
levels of the Smad3 interacting protein, zinc finger DHHC-type containing
4 and col1α2. These data thus demonstrate that while PB lin−/AP+
cells express a number of osteoblastic genes and are capable of mineralization,
they are a relatively quiescent cell population, both in terms of
cell proliferation and matrix synthesis. However, their higher expression
of RANKL and ICAM-1 mRNAs as compared to BM lin−/AP+ cells suggests
a role for the PB lin−/AP+ cells in regulating osteoclastogenesis
that warrants further investigation. Our study also provides “proof-of-concept�
for the use of PB lin−/AP+ cells in clinical-investigative studies,
and identifies several pathways that could potentially regulate rates
of bone loss in postmenopausal women.},
issn = {8756-3282},
keywords = {Osteoporosis, Bone loss, Menopause, Osteoblast, Progenitors},
publisher = {Elsevier Science},
refid = {S8756-3282(10)00532-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S8756328210005326?showall=true}
}
@ARTICLE{Unfried2010,
author = {Unfried, Claudia and Burbach, Guido and Korf, Horst-Werner and Von
Gall, Charlotte},
title = {Melatonin receptor 1-dependent gene expression in the mouse pars
tuberalis as revealed by cDNA microarray analysis and in situ hybridization},
journal = {Journal of Pineal Research},
year = {2010},
volume = {48},
pages = {148--156},
number = {2},
abstract = {Abstract:  Melatonin is an important rhythmic endocrine signal within
the circadian system of mammals. The hypophyseal pars tuberalis (PT)
is a major target for melatonin and shows a high density of melatonin
type 1 receptors (MT1). Melatonin affects expression of clock genes
in PT cells which encode for transcriptional regulators of rhythmic
gene expression. In this study, microarray analysis was performed
to screen for genes coding for transcriptional regulators under the
control of MT1 receptors in the mouse PT. Gene expression levels
were compared between melatonin-proficient mice deficient for MT1
(MT1−/−) and the corresponding wild-type (WT) during mid-subjective
day (CT06, low endogenous melatonin levels) and mid-subjective night
(CT18, high endogenous melatonin levels). In situ hybridization was
used to validate the data obtained by microarray analysis to analyze
the acute effect of daytime melatonin application on gene expression
in the wild-type PT. In the wild-type PT, expression of Tim was higher
during day as compared to night. These day/night differences in gene
expression were not observed in the PT of MT1−/− mice, demonstrating
the impact of MT1-mediated signal transduction pathway. Day-time
application of melatonin acutely affected Tim and Cry1 expression
but not Neurod1 and Npas4 expression. We conclude that melatonin
regulates expression of genes coding for transcriptional regulators
in the PT through MT1 receptors by either acute or long-term mechanisms.},
issn = {1600-079X},
keywords = {bHLH-PAS transcription factor, Cry1, MT1, Neurod1, Npas4, pars tuberalis,
Tim},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-079X.2009.00738.x}
}
@ARTICLE{Unger2005,
author = {Unger, Travis and Korade, Zeljka and Lazarov, Orly and Terrano, David
and Sisodia, Sangram S. and Mirnics, Károly},
title = {True and false discovery in DNA microarray experiments: Transcriptome
changes in the hippocampus of presenilin 1 mutant mice},
journal = {Methods},
year = {2005},
volume = {37},
pages = {261--273},
number = {3},
month = nov,
abstract = {In transcriptome profiling experiments using DNA microarrays, it is
critical to maximize putatively true data discovery while keeping
the false discovery rate at acceptable levels. Using previously published
and verified transcriptome datasets of mice with genetically altered
PS1 physiology, we present a simple, robust, and system-specific
assessment of type I and type II errors in two independent microarray
experimental series. We provide evidence to suggest that for maximizing
true discovery and minimizing false discovery, statistical criteria
alone are inferior to statistical significance plus magnitude of
change criteria. Furthermore, we found that, regardless of the exact
criteria used for determining differential expression, different
data extraction protocols give rise to different discovery and false
discovery rates. In addition, a large proportion of expression differences
were both dataset and analytical approach dependent. The data assessment
methods presented and discussed in this manuscript can be easily
carried out on any microarray dataset using basic spreadsheet functions
as the only tool needed. Finally, we provide an in-depth analysis
of the hippocampal transcriptome of [Delta]E9 hPS1 transgenic mice
and mice with a conditional ablation of the PS1 gene.},
booktitle = {Chip Technology in Neuroscience},
issn = {1046-2023},
keywords = {Presenilin 1, Mutation, Transgenic, Knockout, Alzheimer's disease,
DNA microarray, Hippocampus, DCHIP, MAS5, RMA, Latin square, False
discovery rate, Statistical significance, Data mining, Normalization,
Affymetrix, Brain},
url = {http://www.sciencedirect.com/science/article/B6WN5-4HMF7H7-7/2/f1486c05c424412f5ae07a3b98db26cc}
}
@BOOK{Ungrin2007,
title = {Phenotypic Analysis of Human Embryonic Stem Cells},
publisher = {John Wiley \& Sons, Inc.},
year = {2007},
author = {Ungrin, Mark and O'Connor, Michael and Eaves, Connie and Zandstra,
Peter W.},
pages = {--},
abstract = {Human embryonic stem cells (hESCs) are an important tool for the study
of developmental biology and may one day serve as a source of cells
for regenerative medicine. As no definitive assay for hESC pluripotency
is available, surrogate assays that measure markers or properties
that have been correlated with hESC developmental potential are used
to measure the effects of test conditions on their propagation and
differentiation. This unit presents a range of protocols, including
visual inspection, flow cytometry, immunofluorescence, quantitative
real-time reverse-transcriptase PCR, and a colony-forming assay,
as tools to measure the undifferentiated hESC state. The authors
discuss the advantages and limitations of the various protocols,
and present expected results and discuss potential problems. The
development of quantitative assays of hESC developmental potential
are critical for our understanding of hESC biology. Curr. Protoc.
Stem Cell Biol. 2:1B.3.1-1B.3.25. © 2007 by John Wiley & Sons, Inc.},
booktitle = {Current Protocols in Stem Cell Biology},
issn = {9780470151808},
keywords = {hESC, marker, Oct4, SSEA-3, SSEA-4, Tra-1-60, microscopy, flow cytometry,
quantitative real-time PCR},
url = {http://dx.doi.org/10.1002/9780470151808.sc01b03s2}
}
@ARTICLE{Uppalapati2011,
author = {Uppalapati, Deepthi and Ohta, Naomi and Zhang, Yongqing and Kawabata,
Atsushi and Pyle, Marla M. and Becker, Kevin G. and Troyer, Deryl
and Tamura, Masaaki},
title = {Identification and Characterization of Unique Tumoricidal Genes in
Rat Umbilical Cord Matrix Stem Cells},
journal = {Molecular Pharmaceutics},
year = {2011},
volume = {8},
pages = {1549-1558},
number = {5},
abstract = { Rat umbilical cord matrix stem cells (UCMSC) have been shown to exhibit
a remarkable ability to control rat mammary adenocarcinoma (Mat B
III) cell proliferation both in vivo and in vitro. To study the underlying
mechanisms and genes involved in Mat B III growth attenuation, total
RNA was extracted from the naive rat UCMSC alone and those cocultured
with Mat B III in Transwell culture dishes. Gene expression profiles
of naive rat UCMSC alone and those cocultured with Mat B III cells
were investigated by microarray analysis using an Illumina RatRef-12
Expression BeadChip. The comparison of gene expression profiles between
untreated and cocultured rat UCMSC identified five upregulated candidate
genes (follistatin (FST), sulfatase1 (SULF-1), glucose phosphate
isomerase (GPI), HtrA serine peptidase (HTRA1), and adipocyte differentiation-related
protein (ADRP)) and two downregulated candidate genes (transforming
growth factor, beta-induced, 68 kDa (TGFβI) and podoplanin (PDPN))
based upon the following screening criteria: (1) expression of the
candidate genes should show at least a 1.5-fold change in rat UCMSC
cocultured with Mat B III cells; (2) candidate genes encode secretory
proteins; and (3) they encode cell growth-related proteins. Following
confirmation of gene expression by real-time PCR, ADRP, SULF-1 and
GPI were selected for further analysis. Addition of specific neutralizing
antibodies against these three gene products or addition of gene-specific
siRNA’s individually in cocultures of 1:20 rat UCMSC:Mat B III
cells significantly increased cell proliferation, implying that these
gene products are produced under the cocultured condition and functionally
attenuate cell growth. Immunoprecipitation followed by Western blot
analysis demonstrated that these proteins are indeed secreted into
the culture medium. Individual overexpression of these three genes
in rat UCMSC significantly enhanced UCMSC-dependent inhibition of
cell proliferation in coculture. These results suggest that ADRP,
SULF-1 and GPI act as tumor suppressor genes, and these genes might
be involved in rat UCMSC-dependent growth attenuation of rat mammary
tumors. },
doi = {10.1021/mp2001582},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/mp2001582},
url = {http://pubs.acs.org/doi/abs/10.1021/mp2001582}
}
@ARTICLE{Urakawa2006,
author = {Urakawa, Hidetoshi and Kurata, Shinya and Fujiwara, Taketomo and
Kuroiwa, Daisuke and Maki, Hideaki and Kawabata, Sumiko and Hiwatari,
Takehiko and Ando, Haruo and Kawai, Toshio and Watanabe, Masataka
and Kohata, Kunio},
title = {Characterization and quantification of ammonia-oxidizing bacteria
in eutrophic coastal marine sediments using polyphasic molecular
approaches and immunofluorescence staining},
journal = {Environmental Microbiology},
year = {2006},
volume = {8},
pages = {787--803},
number = {5},
abstract = {Summary Tokyo Bay, a eutrophic bay in Japan, receives nutrients from
wastewater plants and other urban diffuse sources via river input.
A transect was conducted along a line from the Arakawa River into
Tokyo Bay to investigate the ecological relationship between the
river outflow and the distribution, abundance and population structure
of ammonia-oxidizing bacteria (AOB). Five surficial marine sediments
were collected and analysed with polyphasic approaches. Heterogeneity
and genetic diversity of β-AOB populations were examined using restriction
fragment length polymorphism (RFLP) analysis of 16S rRNA and amoA
genes. A shift of the microbial community was detected in samples
along the transect. Both 16S rRNA and amoA genes generated polymorphisms
in the restriction profiles that were distinguishable at each sampling
site. Two 16S rRNA gene libraries were constructed using the reverse
transcription polymerase chain reaction (RT-PCR) method to determine
the major ammonia oxidizers maintaining high cellular rRNA content.
Two major groups were observed in the Nitrosomonas lineage; no Nitrosospira
were detected. The effort to isolate novel AOB was successful; the
isolate dominated in the gene libraries. For quantitative analysis,
a real-time PCR assay targeting the 16S rRNA gene was developed.
The population sizes of β-AOB ranged from 1.6 × 107 to 3.0 × 108 cells g−1
in dry sediments, which corresponded to 0.1–1.1% of the total bacterial
population. An immunofluorescence staining using anti-hydroxylamine
oxidoreductase (HAO) antibody was also tested to obtain complementary
data. The population sizes of ammonia oxidizers ranged between 2.4 × 108
and 1.2 × 109 cells g−1 of dry sediments, which corresponded
to 1.2–4.3% of the total bacterial fraction. Ammonia-oxidizing
bacteria cell numbers deduced by the two methods were correlated
(R = 0.79, P < 0.01). In both methods, the number  of  AOB Â
increased  with  the  distance  from  the river mouth;
ammonia-oxidizing bacteria were most numerous at B30, where the ammonium
concentration in the porewater was markedly lower and the nitrite
concentration was slightly higher than nearby sites. These results
reveal spatial distribution and shifts in the population structure
of AOB corresponding to nutrients and organic inputs from the river
run-off and phytoplankton bloom.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2005.00962.x}
}
@ARTICLE{Urakawa2008,
author = {Urakawa, Hidetoshi and Matsumoto, Junpei and Inaba, Kazuho and Tsuneda,
Satoshi},
title = {DNA microarray mediated transcriptional profiling of Nitrosomonas
europaea in response to linear alkylbenzene sulfonates},
journal = {FEMS Microbiology Letters},
year = {2008},
volume = {282},
pages = {166--173},
number = {2},
abstract = {Abstract Linear alkylbenzene sulfonates (LAS) constitute, quantitatively,
the most important group of synthetic surfactants used today. We
studied the gene expression of Nitrosomonas europaea in response
to LAS using a DNA microarray because ammonia-oxidizers are thought
to be more sensitive to LAS than other microorganisms. Our objective
was to elucidate which genes are expressed for N. europaea in response
to LAS exposure. Microarray analysis and real-time PCR assay revealed
that c. 30 genes were significantly expressed after LAS exposure,
in particular genes associated with energy production and conversion.
Our findings demonstrate that physical disruption of membrane structures,
which contain enzymes associated with energy production and conversion,
might be an important explanation for the high sensitivity of N.
europaea to LAS exposure.},
issn = {1574-6968},
keywords = {Nitrosomonas europaea, ammonia-oxidizing bacteria (AOB), surfactants,
linear alkylbenzene sulfonates (LAS), anionic detergent, DNA microarrays},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2008.01111.x}
}
@ARTICLE{Urayama2007,
author = {Urayama, Kyoji and Guilini, Celia and Messaddeq, Nadia and Hu, Kai
and Steenman, Marja and Kurose, Hitoshi and Ert, Georg and Nebigil,
Canan G.},
title = {The prokineticin receptor-1 (GPR73) promotes cardiomyocyte survival
and angiogenesis},
journal = {FASEB J},
year = {2007},
volume = {21},
pages = {2980--2993},
number = {11},
month = sep,
abstract = {Prokineticins are potent angiogenic factors that bind to two G protein-coupled
receptors to initiate their biological effects. We hypothesize that
prokineticin receptor-1 (PKR1/GPR73) signaling may contribute to
cardiomyocyte survival or repair in myocardial infarction. Since
we showed that prokineticin-2 and PKR1 are expressed in adult mouse
heart and cardiac cells, we investigated the role of prokineticin-2
on capillary endothelial cell and cardiomyocyte function. In cultured
cardiac endothelial cells, prokineticin-2 or overexpression of PKR1
induces vessel-like formation without increasing VEGF levels. In
cardiomyocytes and H9c2 cells, prokineticin-2 or overexpressing PKR1
activates Akt to protect cardiomyocytes against oxidative stress.
The survival and angiogenesis promoting effects of prokineticin-2
in cardiac cells were completely reversed by siRNA-PKR1, indicating
PKR1 involvement. We thus, further investigated whether intramyocardial
gene transfer of DNA encoding PKR1 may rescue the myocardium against
myocardial infarction in mouse model. Transient PKR1 gene transfer
after coronary ligation reduces mortality and preserves left ventricular
function by promoting neovascularization and protecting cardiomyocytes
without altering VEGF levels. In human end-stage failing heart samples,
reduced PKR1 and prokineticin-2 transcripts and protein levels implicate
a more important role for prokineticin-2/PKR1 signaling in heart.
Our results suggest that PKR1 may represent a novel therapeutic target
to limit myocardial injury following ischemic events.--Urayama, K.,
Guilini, C., Messaddeq, N., Hu, K., Steenman, M., Kurose, H., Ert,
G., Nebigil, C. G. The prokineticin receptor-1 (GPR73) promotes cardiomyocyte
survival and angiogenesis},
url = {http://www.fasebj.org/cgi/content/abstract/21/11/2980}
}
@ARTICLE{Urbach2006,
author = {Urbach, Anja and Bruehl, Claus and Witte, Otto W.},
title = {Microarray-based long-term detection of genes differentially expressed
after cortical spreading depression},
journal = {European Journal of Neuroscience},
year = {2006},
volume = {24},
pages = {841--856},
number = {3},
abstract = {Abstract Spreading depression (SD) is a slowly propagating wave of
neuronal depolarization altering ion homeostasis, blood flow and
energy metabolism without causing irreversible damage of the tissue.
As SD has been implicated in several neurological diseases including
migraine and stroke, understanding these disorders requires systematic
knowledge of the processes modified by SD. Thus, we induced repetitive
SD in the rat cerebral cortex by topical application of 3Â m KCl
for ∼2 h and evaluated the kinetics of SD-induced changes in cortical
gene expression for up to 30Â days using Affymetrix RAE230A arrays.
The temporal profile showed a rapid expression of immediate early
genes, genes associated with inflammation, metabolism, stress and
DNA repair, ion transport, and genes that play a role in growth/differentiation.
Stress-response genes could still be detected after 24Â h. At this
time, induced genes were mainly related to the cell membrane and
adhesion, or to the cytoskeleton. A subset of genes was still affected
even 30Â days after SD. Real-time polymerase chain reactions and
immunohistochemistry confirmed the microarray results for several
of the transcripts. Our findings demonstrate a temporal pattern of
gene expression which might promote tissue remodeling and cortical
plasticity, and might probably account for the mediation of neuronal
tolerance towards subsequent ischemia.},
issn = {1460-9568},
keywords = {cerebral cortex, expression profiling, microarray, plasticity, rat,
spreading depression, stroke},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2006.04862.x}
}
@ARTICLE{Urban2006,
author = {Urban, Patrick and Vuaroqueaux, Vincent and Labuhn, Martin and Delorenzi,
Mauro and Wirapati, Pratyaksha and Wight, Edward and Senn, Hans-Jorg
and Benz, Christopher and Eppenberger, Urs and Eppenberger-Castori,
Serenella},
title = {Increased Expression of Urokinase-Type Plasminogen Activator mRNA
Determines Adverse Prognosis in ErbB2-Positive Primary Breast Cancer},
journal = {J. Clin. Oncol.},
year = {2006},
volume = {24},
pages = {4245--4253},
number = {26},
month = sep,
abstract = {PurposeTo evaluate and validate mRNA expression markers capable of
identifying patients with ErbB2-positive breast cancer associated
with distant metastasis and reduced survival. Patients and MethodsExpression
of 60 genes involved in breast cancer biology was assessed by quantitative
real-time PCR (qrt-PCR) in 317 primary breast cancer patients and
correlated with clinical outcome data. Results were validated subsequently
using two previously published and publicly available microarray
data sets with different patient populations comprising 295 and 286
breast cancer samples, respectively. ResultsOf the 60 genes measured
by qrt-PCR, urokinase-type plasminogen activator (uPA or PLAU) mRNA
expression was the most significant marker associated with distant
metastasis-free survival (MFS) by univariate Cox analysis in patients
with ErbB2-positive tumors and an independent factor in multivariate
analysis. Subsequent validation in two microarray data sets confirmed
the prognostic value of uPA in ErbB2-positive tumors by both univariate
and multivariate analysis. uPA mRNA expression was not significantly
associated with MFS in ErbB2-negative tumors. Kaplan-Meier analysis
showed in all three study populations that patients with ErbB2-positive/uPA-positive
tumors exhibited significantly reduced MFS (hazard ratios [HR], 4.3;
95% CI, 1.6 to 11.8; HR, 2.7; 95% CI, 1.2 to 6.2; and, HR, 2.8; 95%
CI, 1.1 to 7.1; all P < .02) as compared with the group with ErbB2-positive/uPA-negative
tumors who exhibited similar outcome to those with ErbB2-negative
tumors, irrespective of uPA status. ConclusionAfter evaluation of
898 breast cancer patients, uPA mRNA expression emerged as a powerful
prognostic indicator in ErbB2-positive tumors. These results were
consistent among three independent study populations assayed by different
techniques, including qrt-PCR and two microarray platforms.},
url = {http://jco.ascopubs.org/cgi/content/abstract/24/26/4245}
}
@ARTICLE{Urbanski2010,
author = {Urbanski, Jennifer M. and Aruda, Amalia and Armbruster, Peter},
title = {A transcriptional element of the diapause program in the Asian tiger
mosquito, Aedes albopictus, identified by suppressive subtractive
hybridization},
journal = {Journal of Insect Physiology},
year = {2010},
volume = {56},
pages = {1147--1154},
number = {9},
month = sep,
abstract = {Many temperate insects cope with the unfavorable conditions of winter
by entering a photoperiodic diapause, but the molecular basis of
this crucial adaptation is not well understood. In temperate populations
of Aedes albopictus, exposure to short-day lengths causes the adult
female to oviposit diapausing eggs. Suppressive subtractive hybridization
(SSH) and quantitative reverse transcription PCR (qRT-PCR) were performed
on RNA isolated from mature (stage V) oocytes of a temperate population
of Ae. albopictus. A total of 438 inserts were sequenced from the
SSH library and 324 unique (non-redundant) sequences were identified.
QRT-PCR experiments were performed for 53 transcripts using a novel
experimental design that included replicate temperate populations
that do undergo photoperiodic diapause and replicate tropical populations
that do not undergo a photoperiodic diapause. There was greater abundance
of an epithelial membrane protein transcript under short-day versus
long-day photoperiods in multiple temperate, but not tropical, populations.
This gene may function during the diapause program by increasing
desiccation resistance or energy reserves. The expression of a phosphatidylethanolamine-binding
protein transcript in response to SD versus LD photoperiod differed
between temperate and tropical populations but does not appear to
be causally involved in diapause. Rapid Amplification of cDNA Ends
(RACE) was performed to determine the entire cDNA sequence of both
transcripts.},
issn = {0022-1910},
keywords = {Photoperiodic diapause, Aedes albopictus, Epithelial membrane protein,
Phosphatidylethanolamine-binding protein, Invasive species},
url = {http://www.sciencedirect.com/science/article/B6T3F-4YNB5Y9-2/2/6550cf5c8339478e3a024f70a2b2db62}
}
@ARTICLE{Uren2011,
author = {Uren, Philip J. and Burns, Suzanne C. and Ruan, Jianhua and Singh,
Kusum K. and Smith, Andrew D. and Penalva, Luiz O. F.},
title = {Genomic Analyses of the RNA-binding Protein Hu Antigen R (HuR) Identify
a Complex Network of Target Genes and Novel Characteristics of Its
Binding Sites},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {37063-37066},
number = {43},
abstract = {The ubiquitously expressed RNA-binding protein Hu antigen R (HuR)
or ELAVL1 is implicated in a variety of biological processes as well
as being linked with a number of diseases, including cancer. Despite
a great deal of prior investigation into HuR, there is still much
to learn about its function. We take an important step in this direction
by conducting cross-linking and immunoprecipitation and RNA sequencing
experiments followed by an extensive computational analysis to determine
the characteristics of the HuR binding site and impact on the transcriptome.
We reveal that HuR targets predominantly uracil-rich single-stranded
stretches of varying size, with a strong conservation of structure
and sequence composition. Despite the fact that HuR sites are observed
in intronic regions, our data do not support a role for HuR in regulating
splicing. HuR sites in 3'-UTRs overlap extensively with predicted
microRNA target sites, suggesting interplay between the functions
of HuR and microRNAs. Network analysis showed that identified targets
containing HuR binding sites in the 3' UTR are highly interconnected.},
doi = {10.1074/jbc.C111.266882},
eprint = {http://www.jbc.org/cgi/reprint/286/43/37063.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/43/37063}
}
@ARTICLE{Urick2006,
author = {Urick, M.E. and Johnson, P.A.},
title = {Cyclooxygenase 1 and 2 mRNA and protein expression in the Gallus
domesticus model of ovarian cancer},
journal = {Gynecologic Oncology},
year = {2006},
volume = {103},
pages = {673--678},
number = {2},
month = nov,
abstract = {Objective. Our purpose was to determine the mRNA and protein expression
of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) in ovarian
tumors and normal ovaries of the hen, which is an excellent model
for human ovarian cancer. Tissue concentrations of prostaglandin
E2 (PGE2) and PGE2 metabolites were also determined.Methods. Tissue
was obtained from ovarian tumor (n = 18) and normal ovary (n = 29)
of 2- to 4-year old Single-comb White Leghorn hens. Quantitative
real-time PCR with Sybr Green was used to quantify the mRNA expression
of COX-1 and COX-2, using 18S expression as an internal control for
COX normalization. Immunohistochemistry using antibodies for COX-1
and COX-2 was used to localize protein expression of each isoform
in a subset of tumor (n = 5) and normal samples (n = 6). For determination
of tissue prostaglandin concentration, tissue was obtained from ovarian
tumor (n = 8) and normal ovary (n = 8). PGE2 and PGE2 metabolites
were measured using competitive enzyme immunoassays (EIAs).Results.
Our results indicate that COX-1 mRNA expression is significantly
higher (P < 0.05) in ovarian tumor samples compared to normal ovaries
while there is no significant difference in expression of COX-2 between
the samples. Immunohistochemistry results support this finding and
show COX-1 expression only in tumor samples and COX-2 expression
unchanged between normal ovary and tumor samples. PGE2 levels are
significantly higher (P < 0.05) in tumor samples compared to normal
ovaries, and there is no significant difference in PGE2 metabolite
levels between the samples.Conclusion. These findings may implicate
COX-1 as a suitable target for the prevention or treatment of ovarian
cancer.},
issn = {0090-8258},
keywords = {Ovarian cancer, Cyclooxygenase, PGE2, Prostaglandins, Hen, Gallus
domesticus},
url = {http://www.sciencedirect.com/science/article/B6WG6-4K7NHFK-4/2/25bf5ab9324dc8103317c6641899d587}
}
@ARTICLE{Urness2010,
author = {Urness, Lisa D. and Paxton, Christian N. and Wang, Xiaofen and Schoenwolf,
Gary C. and Mansour, Suzanne L.},
title = {FGF signaling regulates otic placode induction and refinement by
controlling both ectodermal target genes and hindbrain Wnt8a},
journal = {Developmental Biology},
year = {2010},
volume = {340},
pages = {595--604},
number = {2},
month = apr,
abstract = {The inner ear epithelium, with its complex array of sensory, non-sensory,
and neuronal cell types necessary for hearing and balance, is derived
from a thickened patch of head ectoderm called the otic placode.
Mouse embryos lacking both Fgf3 and Fgf10 fail to initiate inner
ear development because appropriate patterns of gene expression fail
to be specified within the pre-otic field. To understand the transcriptional
"blueprint" initiating inner ear development, we used microarray
analysis to identify prospective placode genes that were differentially
expressed in control and Fgf3-/-;Fgf10-/- embryos. Several genes
in the down-regulated class, including Hmx3, Hmx2, Foxg1, Sox9, Has2,
and Slc26a9 were validated by in situ hybridization. We also assayed
candidate target genes suggested by other studies of otic induction.
Two placode markers, Fgf4 and Foxi3, were down-regulated in Fgf3-/-;Fgf10-/-
embryos, whereas Foxi2, a cranial epidermis marker, was expanded
in double mutants, similar to its behavior when WNT responses are
blocked in the otic placode. Assays of hindbrain Wnt genes revealed
that only Wnt8a was reduced or absent in FGF-deficient embryos, and
that even some Fgf3-/-;Fgf10-/+ and Fgf3-/- embryos failed to express
Wnt8a, suggesting a key role for Fgf3, and a secondary role for Fgf10,
in Wnt8a expression. Chick explant assays showed that FGF3 or FGF4,
but not FGF10, were sufficient to induce Wnt8a. Collectively, our
results suggest that Wnt8a provides the link between FGF-induced
formation of the pre-otic field and restriction of the otic placode
to ectoderm adjacent to the hindbrain.},
booktitle = {Special Section: Gene Regulatory Networks for Development},
issn = {0012-1606},
keywords = {FGF signaling, Otic placode induction, WNT signaling, Microarray analysis},
url = {http://www.sciencedirect.com/science/article/B6WDG-4YDT41M-4/2/5cd16ee504ac311b0af692d635fd300c}
}
@ARTICLE{Usenko2008,
author = {Usenko, Crystal Y. and Harper, Stacey L. and Tanguay, Robert L.},
title = {Fullerene C60 exposure elicits an oxidative stress response in embryonic
zebrafish},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {229},
pages = {44--55},
number = {1},
month = may,
abstract = {Due to its unique physicochemical and optical properties, C60 has
raised interest in commercialization for a variety of products. While
several reports have determined this nanomaterial to act as a powerful
antioxidant, many other studies have demonstrated a strong oxidative
potential through photoactivation. To directly address the oxidative
potential of C60, the effects of light and chemical supplementation
and depletion of glutathione (GSH) on C60-induced toxicity were evaluated.
Embryonic zebrafish were used as a model organism to examine the
potential of C60 to elicit oxidative stress responses. Reduced light
during C60 exposure significantly decreased mortality and the incidence
of fin malformations and pericardial edema at 200 and 300 ppb C60.
Embryos co-exposed to the glutathione precursor, N-acetylcysteine
(NAC), also showed reduced mortality and pericardial edema; however,
fin malformations were not reduced. Conversely, co-exposure to the
GSH synthesis inhibitors, buthionine sulfoximine (BSO) and diethyl
maleate (DEM), increased the sensitivity of zebrafish to C60 exposure.
Co-exposure of C60 or its hydroxylated derivative, C60(OH)24, with
H2O2 resulted in increased mortality along the concentration gradient
of H2O2 for both materials. Microarrays were used to examine the
effects of C60 on the global gene expression at two time points,
36 and 48 h post fertilization (hpf). At both life stages there were
alterations in the expression of several key stress response genes
including glutathione-S-transferase, glutamate cysteine ligase, ferritin,
[alpha]-tocopherol transport protein and heat shock protein 70. These
results support the hypothesis that C60 induces oxidative stress
in this model system.},
issn = {0041-008X},
keywords = {Fullerene, Photoactivation, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6WXH-4RM7MTN-1/2/27ac1007c13b41093fa291822062e809}
}
@ARTICLE{Uthayakumaran2005,
author = {Uthayakumaran, S. and Batey, I.L. and Wrigley, C.W.},
title = {On-the-spot identification of grain variety and wheat-quality type
by Lab-on-a-chip capillary electrophoresis},
journal = {Journal of Cereal Science},
year = {2005},
volume = {41},
pages = {371--374},
number = {3},
month = may,
abstract = {Lab-on-a-chip capillary electrophoresis has been used for identification
of wheat variety and quality type. Analysis of each chip takes 30
minutes for 10 samples, and distinction can be made between members
of a set of 40 commonly grown Australian wheat varieties. Quality
type could be predicted by analysis of the HMW and LMW glutenin subunits.
The technique has also been applied to the separation of proteins
from other grains and legumes, and may also be useful for identifying
variety and/or quality type in these crops.},
issn = {0733-5210},
keywords = {Grain proteins, Capillary electrophoresis, Rapid analysis, Wheat,
Barley, Legumes, Oilseeds},
url = {http://www.sciencedirect.com/science/article/B6WHK-4FC3RWG-1/2/ac9c0ec92495295dcb947c1c30abf8d3}
}
@ARTICLE{Uthayakumaran2006,
author = {Uthayakumaran, S. and Listiohadi, Y. and Baratta, M. and Batey, I.L.
and Wrigley, C.W.},
title = {Rapid identification and quantitation of high-molecular-weight glutenin
subunits},
journal = {Journal of Cereal Science},
year = {2006},
volume = {44},
pages = {34--39},
number = {1},
month = jul,
abstract = {Knowledge of glutenin-subunit composition is important for the prediction
of the genetic potential of breeding lines for dough quality. In
screening for quality using the Glu-1 scoring system, the high-molecular-weight
glutenin subunits (HMW-GS) are especially valuable. This information
is needed at the earliest stages of breeding to ensure that poor-quality
lines are not propagated. Conventionally, glutenin polypeptides have
been identified by SDS gel electrophoresis, but this method is slow,
labour-intensive and only semi-quantitative. The recent Lab-on-a-Chip
technology provides faster micro-fluidic analysis of these proteins
at 1 min per analysis (3 min, given instrument conditioning time).
To screen breeding lines for dough quality, the Lab-on-a-Chip approach
offers quick quantification of specific glutenin subunits with computerized
interpretation. To achieve these objectives, we have allocated subunit
identities to the peaks in the Lab-on-a-Chip sample profiles, using
multiple-deletion lines of wheat and varieties of known composition.
The positions of HMW-GS can be used to identify the composition of
unknown varieties and breeders' lines by computerized comparison
against this established library of profiles from the Lab-on-a-Chip.},
issn = {0733-5210},
keywords = {Wheat-protein composition, Dough-quality prediction, Capillary electrophoresis,
Glutenin subunits, Lab-on-a-Chip, High-molecular-weight glutenin
subunits},
url = {http://www.sciencedirect.com/science/article/B6WHK-4JMM5NX-2/2/c8c0ec962cb3a10e05c997b48a687297}
}
@ARTICLE{Uthe2007,
author = {Uthe, Jolita J. and Royaee, Atabak and Lunney, Joan K. and Stabel,
Thomas J. and Zhao, Shu-Hong and Tuggle, Christopher K. and Bearson,
Shawn M.D.},
title = {Porcine differential gene expression in response to Salmonella enterica
serovars Choleraesuis and Typhimurium},
journal = {Molecular Immunology},
year = {2007},
volume = {44},
pages = {2900--2914},
number = {11},
month = apr,
issn = {0161-5890},
keywords = {Salmonella, Transcriptional profiling, Swine, Immune response, Host-specificity},
url = {http://www.sciencedirect.com/science/article/B6T9R-4N6FV65-2/2/39228cf7b14e7b032fdbb950abe756ec}
}
@ARTICLE{Uthe2006,
author = {Uthe, Jolita J. and Stabel, Thomas J. and Zhao, Shu-hong and Tuggle,
Christopher K. and Bearson, Shawn M.D.},
title = {Analysis of porcine differential gene expression following challenge
with Salmonella enterica serovar Choleraesuis using suppression subtractive
hybridization},
journal = {Veterinary Microbiology},
year = {2006},
volume = {114},
pages = {60--71},
number = {1-2},
month = apr,
abstract = {Swine-adapted Salmonella enterica subsp. enterica serovar Choleraesuis
(S. Choleraesuis) is the pathogen most frequently isolated from diseased
pigs and may affect host gene expression in a species-specific manner.
To characterize the porcine transcriptional response to S. Choleraesuis
infection, the mRNA profiles from the mesenteric lymph nodes of three
non-infected and three experimentally infected pigs at 24 h post-inoculation
were analyzed by suppression subtractive hybridization (SSH). Forty-four
up-regulated and 44 down-regulated genes were revealed by differential
cDNA screening of 384 forward and 288 reverse subtracted cDNA clones.
The DNA sequence of the cDNA clones identified genes with a role
in a variety of cellular functions as well as gene products of unknown
function. Seven up-regulated genes (CXCL10, CXCR4, SDCBP, DNAJA1,
HSPH1, HSP90 and ANXA5) and two functionally related genes (HSP70
and DNAJA4:pDJA1) were selected for further analysis based on their
predicted roles in infection and immunity. Real-time RT-PCR was performed
using RNA collected from a time course of infection spanning from
the acute phase (8 h) to the chronic phase (21 days) to confirm and
quantitate the up-regulation of the SSH-enriched genes. Correlating
with the clinical signs of infection (fever, diarrhea and lethargy),
the most dramatic induction of gene expression for all nine genes
occurred at 48 h post-inoculation. This investigation further defines
the porcine response to a host-adapted strain of Salmonella by revealing
the differential expression of genes with a role in a variety of
host cellular functions including innate immunity and cytoskeleton
regulation.},
issn = {0378-1135},
keywords = {Salmonella enterica serovar Choleraesuis, Swine, Suppression subtractive
hybridization, Real-time RT-PCR, Differential gene expression},
url = {http://www.sciencedirect.com/science/article/B6TD6-4HVDYT9-1/2/e6877ed7309ba5180bb39723e6d074c2}
}
@ARTICLE{Utheim2009,
author = {Utheim, Tor P. and Raeder, Sten and Olstad, Ole K. and Utheim, Oygunn
A. and de La Paz, Maria and Cheng, Robert and Huynh, Trang T. and
Messelt, Edward and Roald, Borghild and Lyberg, Torstein},
title = {Comparison of the Histology, Gene Expression Profile, and Phenotype
of Cultured Human Limbal Epithelial Cells from Different Limbal Regions},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {5165--5172},
number = {11},
month = nov,
abstract = {Purpose.To investigate whether human limbal epithelial cells (HLECs)
derived from various regions of the limbus exhibit differences in
gene expression and epithelial characteristics. Methods.HLECs were
derived from explants taken from the superior, nasal, inferior, and
temporal limbus and cultured for 21 days. Whole genome transcript
profiling was performed with a gene microarray. The microarray results
were validated by using RT-PCR. Epithelial morphology was studied
with light microscopy and transmission electron microscopy, and phenotype
was evaluated by immunohistochemistry. Results.Epithelial outgrowth
was present in most cultures of superior origin (88%) in contrast
to cultures of temporal origin (38%). The epithelial thickness and
number of cell layers were significantly greater in cultures of superior
origin than in cultures from inferior and temporal areas. TRIM36,
OSR2, and RHOU, which are involved in morphogenesis, were significantly
differentially expressed in the superior region, compared with the
other regions. Proposed limbal stem cell, progenitor, and differentiation
markers were not differentially expressed. The uniform gene expression
of ocular surface markers correlated with homogeneous immunostaining
of corresponding protein markers in HLEC cultures from all regions,
demonstrating an undifferentiated phenotype (p63+, {Delta}Np63{alpha}+,
ABCG2+, K19+, vimentin+, integrin {beta}1+, nestin-, K3-, K5+, and
E-cadherin+). Conclusions.No major transcriptional or phenotypic
differences were observed in cultured HLECs derived from different
regions of the limbus. However, explants of superior origin demonstrated
the highest outgrowth success rate and generated epithelia with greater
epithelial thickness and number of cell layers, which may prove useful
for transplantation purposes.},
url = {http://www.iovs.org/cgi/content/abstract/50/11/5165}
}
@ARTICLE{Utikal2006,
author = {Utikal, Jochen and Gratchev, Alexei and Muller-Molinet, Isabelle
and Oerther, Sandra and Kzhyshkowska, Julia and Arens, Norbert and
Grobholz, Rainer and Kannookadan, Sheila and Goerdt, Sergij},
title = {The expression of metastasis suppressor MIM/MTSS1 is regulated by
DNA methylation},
journal = {Int. J. Cancer},
year = {2006},
volume = {119},
pages = {2287--2293},
number = {10},
abstract = {Abstract 10.1002/ijc.22106.abs MIM/MTSS1 was initially described as
a gene missing in invasive bladder cancer cell lines. Functional
analysis revealed that MIM is an actin binding protein involved in
the regulation of actin cytoskeleton dynamics. MIM was shown to be
sonic hedgehog (Shh) signaling dependent and synergizes with the
effects of Gli transcription factors. Overexpression of MIM in cell
lines leads to the inhibition of cell proliferation. In this study,
we showed that the inhibition of cell growth by MIM is anchorage
independent. We identified and cloned the promoter region of MIM
and located the main promoter activity to 276 bp of 5′ flanking
sequence sited within a CpG island. Analysis of DNA methylation using
bisulphite sequencing revealed that MIM promoter is methylated in
its 5′ region in cells and tissue samples with reduced endogenous
MIM expression. Using luciferase reporter assay, we demonstrated
that nonmethylated MIM promoter has a similar activity in cell lines
with different endogenous MIM expression. Inhibition of DNA methylation
by 5-Aza-2′-deoxycytidine led to upregulation of MIM expression
in a low expressing cell line. In conclusion, we clearly demonstrate
here that the expression of metastasis suppressor MIM is regulated
by DNA methylation of a CpG island within its promoter region. ©
2006 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {actin, tumor suppressor, carcinoma, 5-Aza-2′-deoxycytidine, BEG4},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22106}
}
@ARTICLE{Utsunomiya2004,
author = {Utsunomiya, Tohru and Okamoto, Masahiro and Hashimoto, Masaji and
Yoshinaga, Keiji and Shiraishi, Takeshi and Tanaka, Fumiaki and Mimori,
Koshi and Inoue, Hiroshi and Watanabe, Goro and Barnard, Graham F.
and Mori, Masaki},
title = {A gene-expression signature can quantify the degree of hepatic fibrosis
in the rat},
journal = {Journal of Hepatology},
year = {2004},
volume = {41},
pages = {399--406},
number = {3},
month = sep,
abstract = {Backgrounds/Aims A more accurate and objective quantification of hepatic
fibrosis would provide clinically useful information for the monitoring
of chronic liver disease progression and therapy recommendation.Methods
Using a cDNA microarray of 14,814 clones, we analyzed the gene-expression
profiles of fibrotic livers in a rat model.Results We identified
750 up- and 345 down-regulated genes by combining a signal-to-noise
score and a random permutation test (P<0.01). The functions of these
genes provided insight into the underlying molecular mechanisms of
both structural remodeling and functional deficits in cirrhosis.
To quantify the extent of liver fibrosis, we have generated for the
first time a [`]genetic fibrosis index' based on gene-expression
profiling of 95 genes by combining a Pearson correlation coefficient
and a [`]leave-one-out' cross-validation procedure. This technique
based on a supervised learning analysis correctly quantified the
various degrees of fibrosis in both 20 training samples (R2=0.829,
P<0.001) and 6 test samples (R2=0.822, P<0.05).Conclusions Our method
will assist researchers in identifying rational targets for intervention
and might help clinicians to objectively monitor the severity of
liver fibrosis.},
issn = {0168-8278},
keywords = {Liver fibrosis, cDNA microarray, Scoring system, Fibrogenesis, Carcinogenesis},
url = {http://www.sciencedirect.com/science/article/B6W7C-4CVR4J0-2/2/bda6f77eec260aaff38177b15205e85f}
}
@ARTICLE{Uyeno2008,
author = {Uyeno, Yutaka and Sekiguchi, Yuji and Kamagata, Yoichi},
title = {Impact of consumption of probiotic lactobacilli-containing yogurt
on microbial composition in human feces},
journal = {International Journal of Food Microbiology},
year = {2008},
volume = {122},
pages = {16--22},
number = {1-2},
month = feb,
abstract = {An in vivo study was carried out to determine the effect of consuming
probiotic lactobacilli-containing yogurt on the composition of microbiota
in the human gut. Fifteen healthy adults ingested a daily serving
of one of three commercial yogurts (two of the products contained
a probiotic lactobacilli strain) for 20 days. Fecal samples at defined
time points before, during, and after the period of yogurt ingestion
were collected and analyzed. The fecal population of lactobacilli
was determined by a culture-based method and subsequent colony PCR
for the identification of species. Six predominant bacterial groups
in the fecal samples were quantitatively determined based on a sequence-specific
SSU rRNA cleavage method coupled with a suite of oligonucleotide
probes, which was optimized for the target-specific detection of
bacterial groups inhabiting human feces. In the ingestion period,
one probiotic strain was detected in the feces of all five subjects
who consumed the yogurt containing the strain, while the other strain
was detected in three of another five subjects. The population levels
of the two major groups (Bacteroides and Prevotella, and the Clostridium
coccoides-Eubacterium rectale group) in the fecal samples tended
to change in response to the ingestion but the change did not seem
to be dependent on the product-specific property of each yogurt.
These results suggest that the human fecal bacterial community could
be altered by ingesting yogurt, although whether probiotic lactobacilli
are present or absent in the yogurt does not seem to be a factor
in this change.},
issn = {0168-1605},
keywords = {Probiotics, Human intestine, Microbial community, DNA probe, rRNA
cleavage},
url = {http://www.sciencedirect.com/science/article/B6T7K-4R5VYK8-5/2/da17dfdcca27becc35215645975fa326}
}
@ARTICLE{Uyeno2004,
author = {Uyeno, Yutaka and Sekiguchi, Yuji and Sunaga, Akiko and Yoshida,
Hiroki and Kamagata, Yoichi},
title = {Sequence-Specific Cleavage of Small-Subunit (SSU) rRNA with Oligonucleotides
and RNase H: a Rapid and Simple Approach to SSU rRNA-Based Quantitative
Detection of Microorganisms},
journal = {Appl. Envir. Microbiol.},
year = {2004},
volume = {70},
pages = {3650--3663},
number = {6},
month = jun,
abstract = {A rapid and simple approach to the small-subunit (SSU) rRNA-based
quantitative detection of a specific group of microorganisms in complex
ecosystems has been developed. The method employs sequence-specific
cleavage of rRNA molecules with oligonucleotides and RNase H. Defined
mixtures of SSU rRNAs were mixed with an oligonucleotide (referred
to as a "scissor probe") that was specifically designed to hybridize
with a particular site of targeted rRNA and were subsequently digested
with RNase H to proceed to sequence-dependent rRNA scission at the
hybridization site. Under appropriate reaction conditions, the targeted
rRNAs were correctly cut into two fragments, whereas nontargeted
rRNAs remained intact under the same conditions. The specificity
of the cleavage could be properly adjusted by controlling the hybridization
stringency between the rRNA and the oligonucleotides, i.e., by controlling
either the temperature of the reaction or the formamide concentration
in the hybridization-digestion buffer used for the reaction. This
enabled the reliable discrimination of completely matched rRNA sequences
from single-base mismatched sequences. For the detection of targeted
rRNAs, the resulting RNA fragment patterns were analyzed by gel electrophoresis
with nucleotide-staining fluorescent dyes in order to separate cleaved
and intact rRNA molecules. The relative abundance of the targeted
SSU rRNA fragments in the total SSU rRNA could easily be calculated
without the use of an external standard by determining the signal
intensity of individual SSU rRNA bands in the electropherogram. This
approach provides a fast and easy means of identification, detection,
and quantification of a particular group of microbes in clinical
and environmental specimens based on rRNA.},
url = {http://aem.asm.org/cgi/content/abstract/70/6/3650}
}
@ARTICLE{Uyeno2010,
author = {Uyeno, Yutaka and Sekiguchi, Yuji and Tajima, Kiyoshi and Takenaka,
Akio and Kurihara, Mitsunori and Kamagata, Yoichi},
title = {An rRNA-based analysis for evaluating the effect of heat stress on
the rumen microbial composition of Holstein heifers},
journal = {Anaerobe},
year = {2010},
volume = {16},
pages = {27--33},
number = {1},
month = feb,
abstract = {We performed a set of heifer feeding trials to investigate the effect
of heat and humidity stresses on the rumen bacterial molecular diversity
of Holstein heifers (Tajima K, Nonaka I, Higuchi K, Takusari N, Kurihara
M, Takenaka A, et al. Anaerobe 2007;13:57-64). To further characterize
the response of the microbial community to the physiological changes
caused by the stresses, we evaluated changes in the ruminal bacterial
community composition in the same trials by applying an RNA-based
method (sequence-specific small-subunit (SSU) rRNA cleavage method),
which was optimized for a comprehensive description of the predominant
bacterial groups inhabiting the rumen. Four Holstein heifers were
kept at three temperatures (20 °C, 28 °C, 33 °C) in a climatic chamber
for two weeks each, and rumen fluid samples were obtained on the
last day of each temperature experiment. For quantitative detection,
we applied a set of 15 oligonucleotide probes, including those targeting
taxa comprised of uncultured rumen bacteria (URB) belonging to phylum
Firmicutes, to the RNAs extracted from the fluid samples. The relative
populations of the Clostridium coccoides-Eubacterium rectale group,
and the genus Streptococcus increased, and that of the genus Fibrobacter
decreased in response to increasing temperature both in the first
(nine months old, 80% relative humidity) and second (15 months old,
60% relative humidity) experiments. In addition, the population of
a defined URB group was higher at 33 °C than at 20 °C in the second
trial, whereas one of the other URB groups showed a decreasing trend
with the temperature rise. These results indicate that the exposure
to heat affects the population levels of specific bacterial groups
in the ruminal microbial community.},
issn = {1075-9964},
keywords = {DNA probe, rRNA digestion, Heat stress, rumen, Microbial community},
url = {http://www.sciencedirect.com/science/article/B6W9T-4W8TW9G-1/2/b414c1ef8979618d2b9cef94fc88ebe1}
}
@ARTICLE{Uyeno2007,
author = {Uyeno, Y. and Sekiguchi, Y. and Tajima, K. and Takenaka, A. and Kurihara,
M. and Kamagata, Y.},
title = {Evaluation of group-specific, 16S rRNA-targeted scissor probes for
quantitative detection of predominant bacterial populations in dairy
cattle rumen},
journal = {Journal of Applied Microbiology},
year = {2007},
volume = {103},
pages = {1995--2005},
number = {5},
abstract = {Abstract Aims:  To develop a suite of group-specific, rRNA-targeted
oligonucleotide scissor probes for the quantitative detection of
the predominant bacterial groups within the ruminal microbial community
with the rRNA cleavage reaction-mediated microbial quantification
method. Methods and Results:  Oligonucleotides that complement
the conserved sites of the 16S rRNA of phylogenetically defined groups
of bacteria that significantly contribute to the anaerobic fermentation
of carbohydrates in ruminal ecosystems were selected from among published
probes or were newly designed. For each probe, target-specific rRNA
cleavage was achieved by optimizing the formamide concentration in
the reaction mixture. The set of scissor probes was then used to
analyse the bacterial community in the rumen fluids of four healthy
dairy cows. In the rumen fluid samples, the genera Bacteroides/Prevotella
and Fibrobacter and the Clostridium coccoides-Eubacterium rectale
group were detected in abundance, accounting for 44–48%, 2·9–10%,
and 9·1–10% of the total 16S rRNA, respectively. The coverage
with the probe set was 71–78% of the total bacterial 16S rRNA.
Conclusions:  The probe set coupled with the sequence-specific
small-subunit rRNA cleavage method can be used to analyse the structure
of a ruminal bacterial community. Significance and Impact of the
Study:  The probe set developed in this study provides a tool for
comprehensive rRNA-based monitoring of the community members that
dominate ruminal ecosystems. As the ruminal microbial community can
be perturbed, it is important to track its dynamics by analysing
microbiological profiles under specific conditions. The method described
here will provide a convenient approach for such tracking.},
issn = {1365-2672},
keywords = {DNA probe, microbial community, quantification, rRNA digestion, rumen},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2672.2007.03443.x}
}
@ARTICLE{Uzan2009,
author = {Uzan, Catherine and Andre, Fabrice and Scott, Veronique and Laurent,
Isabelle and Azria, Elie and Suciu, Voichita and Balleyguier, Corinne
and Lacroix, Ludovic and Delaloge, Suzette and Vielh, Philippe},
title = {Fine-needle aspiration for nucleic acid-ased molecular analyses in
breast cancer},
journal = {Cancer Cytopathology},
year = {2009},
volume = {117},
pages = {32--39},
number = {1},
abstract = {Abstract 10.1002/cncy.20008.abs BACKGROUND: With the widespread development
of genomic analysis, an accurate and quick method for obtaining high-quality
nucleic acids is needed. The objective of the current study was to
evaluate the quality and potential use of material obtained from
fine-needle aspiration cytology (FNAC). METHODS: Ultrasound- or palpation-guided
FNAC was performed in 124 consecutive patients who had nodular breast
lesions. The authors evaluated the amount of messenger RNA (mRNA)
obtained, its quality through the RNA Integrity (RIN) score, and
the factors that influenced both. For malignant lesions, the authors
attempted to correlate estrogen receptor 1 (ESR1) and HER-2 (c-erb–B2)
mRNA expression measured by real-time quantitative polymerase chain
reaction with estrogen receptor and HER-2 detection obtained by immunohistochemistry
(IHC) and/or fluorescent in situ hybridization (FISH) on the surgical
specimen. RESULTS: The amount of mRNA obtained was >1 μg in 89.5%
of 124 samples (43 benign lesions and 81 adenocarcinomas). Overall,
59.3% of samples yielded >1 μg RNA with a RIN score >6. The most
significant predictors of quality and quantity of mRNA were the cytopathologist
who sampled the tumors and a diagnosis of cancer versus benign lesion.
The median ESR1 expression level, which was expressed as the polymerase
chain reaction cycle threshold (CT) level minus the average 18S value
(dct), was 17.7 dct in patients with estrogen receptor-negative tumors
and 11.1 dct in patients with estrogen receptor-positive tumors,.
The median HER-2 expression level was 15.1 dct in patients with HER-2-negative
tumors and 10.7 dct in patients with HER-2-positive tumors. mRNA
expression was concordant with the IHC/FISH evaluation in 90.3% of
patients for estrogen receptor status and in 98.5% of patients for
HER-2 status. CONCLUSIONS: In 70% of cases, FNAC of breast lesions
in well trained hands allowed the extraction of mRNA suitable for
gene expression analysis. Cancer (Cancer Cytopathol) 2009. © 2009
American Cancer Society.},
issn = {1934-6638},
keywords = {breast cancer, fine-needle aspiration cytology, HER-2, estrogen receptor,
gene expression},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/cncy.20008}
}
@ARTICLE{Uzun2009,
author = {Uzun, Alper and Rodriguez-Osorio, Nelida and Kaya, Abdullah and Wang,
Hongfeng and Parrish, John and Ilyin, Valentin and Memili, Erdogan},
title = {Functional genomics of HMGN3a and SMARCAL1 in early mammalian embryogenesis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {183},
number = {1},
abstract = {BACKGROUND:Embryonic genome activation (EGA) is a critical event for
the preimplantation embryo, which is manifested by changes in chromatin
structure, transcriptional machinery, expression of embryonic genes,
and degradation of maternal transcripts. The objectives of this study
were to determine transcript abundance of HMGN3a and SMARCAL1 in
mature bovine oocytes and early bovine embryos, to perform comparative
functional genomics analysis of these genes across mammals.RESULTS:New
annotations of both HMGN3a and SMARCAL1 were submitted to the Bovine
Genome Annotation Submission Database at BovineGenome.org. Careful
analysis of the bovine SMARCAL1 consensus gene set for this protein
(GLEAN_20241) showed that the NCBI protein contains sequencing errors,
and that the actual bovine protein has a high degree of homology
to the human protein. Our results showed that there was a high degree
of structural conservation of HMGN3a and SMARCAL1 in the mammalian
species studied. HMGN3a transcripts were present at similar levels
in bovine matured oocytes and 2–4-cell embryos but at higher levels
in 8–16-cell embryos, morulae and blastocysts. On the other hand,
transcript levels of SMARCAL1 decreased throughout preimplantation
development.CONCLUSION:The high levels of structural conservation
of these proteins highlight the importance of chromatin remodeling
in the regulation of gene expression, particularly during early mammalian
embryonic development. The greater similarities of human and bovine
HMGN3a and SMARCAL1 proteins may suggest the cow as a valuable model
to study chromatin remodeling at the onset of mammalian development.
Understanding the roles of chromatin remodeling proteins during embryonic
development emphasizes the importance of epigenetics and could shed
light on the underlying mechanisms of early mammalian development.},
doi = {10.1186/1471-2164-10-183},
issn = {1471-2164},
pubmedid = {19393058},
url = {http://www.biomedcentral.com/1471-2164/10/183}
}
@ARTICLE{Vacca2005,
author = {Vacca, Angelo and Scavelli, Claudio and Montefusco, Vittorio and
Di Pietro, Giulia and Neri, Antonino and Mattioli, Michela and Bicciato,
Silvio and Nico, Beatrice and Ribatti, Domenico and Dammacco, Franco
and Corradini, Paolo},
title = {Thalidomide Downregulates Angiogenic Genes in Bone Marrow Endothelial
Cells of Patients With Active Multiple Myeloma},
journal = {J. Clin. Oncol.},
year = {2005},
volume = {23},
pages = {5334--5346},
number = {23},
month = aug,
abstract = {PURPOSE: To study the antiangiogenic effect of thalidomide. PATIENTS
AND METHODS: The expression of key angiogenic genes was studied in
bone marrow endothelial cells (ECs) of patients with active and nonactive
multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated
(MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's
sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs)
following exposure to therapeutic doses of thalidomide. RESULTS:
Thalidomide markedly downregulates the genes in a dose-dependent
fashion in active MMECs and KS cell line, but upregulates them or
is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs.
Secretion of vascular endothelial growth factor (VEGF), basic fibroblast
growth factor (bFGF) and hepatocyte growth factor also diminishes
according to the dose in culture conditioned media (CM) of active
MMECs and KS, whereas it does not change in the other CM. CONCLUSION:
Inhibition by thalidomide is probably confined to the genes of active
MMECs and KS. This would account for its higher efficacy in these
diseases.},
url = {http://jco.ascopubs.org/cgi/content/abstract/23/23/5334}
}
@ARTICLE{Vacca2006,
author = {Vacca, Angelo and Scavelli, Claudio and Serini, Guido and Di Pietro,
Giulia and Cirulli, Teresa and Merchionne, Francesca and Ribatti,
Domenico and Bussolino, Federico and Guidolin, Diego and Piaggio,
Giovanna and Bacigalupo, Andrea and Dammacco, Franco},
title = {Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone
marrow endothelial cells of patients with multiple myeloma},
journal = {Blood},
year = {2006},
volume = {108},
pages = {1661--1667},
number = {5},
month = sep,
abstract = {Vascular endothelial growth factor165 (VEGF165) and semaphorin3A (SEMA3A)
elicit pro- and antiangiogenic signals respectively in endothelial
cells (ECs) by binding to their receptors VEGFR-2, neuropilin-1 (NRP1),
and plexin-A1. Here we show that the VEGF165-driven angiogenic potential
of multiple myeloma (MM) ECs is significantly higher than that of
monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs)
and human umbilical vein (HUV) ECs. This is probably due to a constitutive
imbalance of endogenous VEGF165/SEMA3A ratio, which leans on VEGF165
in MMECs but on SEMA3A in MGECs and HUVECs. Exogenous VEGF165 induces
SEMA3A expression in MGECs and HUVECs, but not in MMECs. Moreover,
by counteracting VEGF165 activity as efficiently as an anti-VEGFR-2
antibody, exogenous SEMA3A restrains the over-angiogenic potential
of MMECs. Our data indicate that loss of endothelial SEMA3A in favor
of VEGF165 could be responsible for the angiogenic switch from MGUS
to MM.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/108/5/1661}
}
@ARTICLE{Vachova2004,
author = {Vachova, Libuse and Devaux, Frederic and Kucerova, Helena and Ricicova,
Marketa and Jacq, Claude and Palkova, Zdena},
title = {Sok2p Transcription Factor Is Involved in Adaptive Program Relevant
for Long Term Survival of Saccharomyces cerevisiae Colonies},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {37973--37981},
number = {36},
month = sep,
abstract = {Volatile ammonia functions as a long range alarm signal important
for the transition of yeast colonies to their adaptive alkali developmental
phase and for their consequent long term survival. Cells of aged
Saccharomyces cerevisiae sok2 colonies deleted in the gene for Sok2p
transcription factor are not able to release a sufficient amount
of ammonia out of the cells, they are more fragile than cells of
wild type colonies, and they exhibit a survival defect. Genome-wide
analysis on gene expression differences between sok2 and WT colonies
revealed that sok2 colonies are not able to switch on the genes of
adaptive metabolisms effectively and display unbalanced expression
and activity of various enzymes involved in cell protection against
oxidative damage. Impaired amino acid metabolism and insufficient
activation of genes for putative ammonium exporters Ato and of those
for some other membrane transporters may be responsible for observed
defects in ammonia production. Thus, Sok2p appears to be an important
regulator of S. cerevisiae colony development. Gene expression differences
caused by its absence in colonies differ from those described previously
in liquid cultures, which suggests a pleiotropic effect of Sok2p
under different conditions.},
url = {http://www.jbc.org/cgi/content/abstract/279/36/37973}
}
@ARTICLE{Vachova2009,
author = {Vachova, Libuse and Kucerova, Helena and Devaux, Frederic and Ulehlova,
Miroslava and Palkova, Zdena},
title = {Metabolic diversification of cells during the development of yeast
colonies},
journal = {Environmental Microbiology},
year = {2009},
volume = {11},
pages = {494--504},
number = {2},
abstract = {Summary Microorganisms in nature form organized multicellular structures
(colonies, biofilms) possessing properties absent in individual cells.
These are often related to the better ability of communities to survive
long-lasting starvation and stress and include mechanisms of adaptation
and cell specialization. Thus, yeast colonies pass through distinct
developmental phases characterized by changes in pH and the production
of ammonia-signalling molecules. Here, we show that Saccharomyces
cerevisiae colony transition between major developmental phases (first
acidic, alkali, second acidic) is accompanied by striking transcription
changes, while the development within each particular phase is guided
mostly at the post-transcriptional level. First- and second-acidic-phase
colonies markedly differ. Second-acidic-phase colonies maintain the
adaptive metabolism activated in the ammonia-producing period, supplemented
by additional changes, which begin after colonies enter the second
acidic phase. Cells with particular properties are not homogenously
dispersed throughout the colony population, but localize to specific
colony regions. Thus, cells located at the colony margin are able
to export higher amounts of ammonium than central cells and to activate
an adaptive metabolism. In contrast, central chronologically aged
cells are unable to undergo these changes but they maintain higher
levels of various stress-defence enzymes. These divergent properties
of both cell types determine their consequent dissimilar fate.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2008.01789.x}
}
@ARTICLE{Vaerenbergh2010,
author = {Vaerenbergh, Inge Van and McIntire, Ramsey and Lommel, Leentje Van
and Devroey, Paul and Giudice, Linda and Bourgain, Claire},
title = {Gene expression during successful implantation in a natural cycle},
journal = {Fertil Steril},
year = {2010},
volume = {93},
pages = {268.e15--268.e18},
number = {1},
month = jan,
abstract = {To determine the human endometrial transcriptome during embryonic
implantation. Case report. Tertiary fertility center. A 24-year-old
woman who inadvertently became pregnant during an endometrial biopsy
procedure. An endometrial biopsy was performed with a Pipelle device
during the midluteal phase (days 19–21) of the cycle; blood samples
for hormonal assessments were collected and a transvaginal ultrasound
was performed. Gene expression analysis of the endometrium during
the window of implantation (during the implantation of an embryo)
in a natural cycle. Localization of selected genes in endometrial
tissue with immunohistochemistry. A total of 394 probe sets were
differentially expressed in the pregnant sample when compared with
the midsecretory phase nonpregnant endometrial samples. Different
gene networks were involved, and selected genes from these signaling
pathways were confirmed at the protein level. Endometrial gene expression
of a pregnant patient in a natural cycle is significantly different
from nonpregnant patients during the midsecretory phase.},
issn = {0015-0282},
keywords = {Gene expression, implantation, pregnancy, endometrium, natural cycle},
publisher = {Elsevier for the American Society for Reproductive Medicine.},
refid = {S0015-0282(09)03596-1},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0015028209035961?showall=true}
}
@ARTICLE{Vaes2006,
author = {Vaes, Bart L.T. and Ducy, Patricia and Sijbers, Anneke M. and Hendriks,
José M.A. and van Someren, Eugene P. and de Jong, Nanning G. and
van den Heuvel, Edwin R. and Olijve, Wiebe and van Zoelen, Everardus
J.J. and Dechering, Koen J.},
title = {Microarray analysis on Runx2-deficient mouse embryos reveals novel
Runx2 functions and target genes during intramembranous and endochondral
bone formation},
journal = {Bone},
year = {2006},
volume = {39},
pages = {724--738},
number = {4},
month = oct,
abstract = {A major challenge in developmental biology is to correlate genome-wide
gene expression modulations with developmental processes in vivo.
In this study, we analyzed the role of Runx2 during intramembranous
and endochondral bone development, by comparing gene expression profiles
in 14.5 dpc wild-type and Runx2 (-/-) mice. A total of 1277, 606
and 492 transcripts were found to be significantly modulated by Runx2
in calvaria, forelimbs and hindlimbs, respectively. Bioinformatics
analysis indicated that Runx2 not only controls the processes of
osteoblast differentiation and chondrocyte maturation, but may also
play a role in axon formation and hematopoietic cell commitment during
bone development. A total of 41 genes are affected by the Runx2 deletion
in both intramembranous and endochondral bone, indicating common
pathways between these two developmental modes of bone formation.
In addition, we identified genes that are specifically involved in
endochondral ossification. In conclusion, our data show that a comparative
genome-wide expression analysis of wild-type and mutant mouse models
allows the examination of mutant phenotypes in complex tissues.},
issn = {8756-3282},
keywords = {Microarray, Runx2, Mouse, Bone, Development},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4K5ST78-3/2/57ec5122d25583a06c60c004648d46fd}
}
@ARTICLE{Vaez2008,
author = {Vaez, Mohsen and Follett, Sarah and Bed'hom, Bertrand and Gourichon,
David and Tixier-Boichard, Michèle and Burke, Terry},
title = {A single point-mutation within the melanophilin gene causes the lavender
plumage colour dilution phenotype in the chicken},
journal = {BMC Genetics},
year = {2008},
volume = {9},
pages = {7},
number = {1},
abstract = {BACKGROUND:The lavender phenotype in the chicken causes the dilution
of both black (eumelanin) and red/brown (phaeomelanin) pigments.
Defects in three genes involved in intracellular melanosomal transport,
previously described in mammals, give rise to similar diluted pigmentation
phenotypes as those seen in lavender chickens.RESULTS:We have used
a candidate-gene approach based on an expectation of homology with
mammals to isolate a gene involved in pigmentation in chicken. Comparative
sequence analysis of candidate genes in the chicken identified a
strong association between a mutation in the MLPH gene and the diluted
pigmentation phenotype. This mutation results in the amino acid change
R35W, at a site also associated with similar phenotypes in mice,
humans and cats.CONCLUSION:This is the first time that an avian species
with a mutation in the MLPH gene has been reported.},
doi = {10.1186/1471-2156-9-7},
issn = {1471-2156},
owner = {Meike Kuschel},
pubmedid = {18197963},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2156/9/7}
}
@ARTICLE{Vagin2008,
author = {Vagin, Olga and Tokhtaeva, Elmira and Yakubov, Iskandar and Shevchenko,
Eugenia and Sachs, George},
title = {Inverse Correlation between the Extent of N-Glycan Branching and
Intercellular Adhesion in Epithelia: CONTRIBUTION OF THE Na,K-ATPase
1 SUBUNIT},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {2192--2202},
number = {4},
month = jan,
abstract = {The majority of cell adhesion molecules are N-glycosylated, but the
role of N-glycans in intercellular adhesion in epithelia remains
ill-defined. Reducing N-glycan branching of cellular glycoproteins
by swainsonine, the inhibitor of N-glycan processing, tightens and
stabilizes cell-cell junctions as detected by a 3-fold decrease in
the paracellular permeability and a 2-3-fold increase in the resistance
of the adherens junction proteins to extraction by non-ionic detergent.
In addition, exposure of cells to swainsonine inhibits motility of
MDCK cells. Mutagenic removal of N-glycosylation sites from the Na,K-ATPase
{beta}1 subunit impairs cell-cell adhesion and decreases the effect
of swainsonine on the paracellular permeability of the cell monolayer
and also on detergent resistance of adherens junction proteins, indicating
that the extent of N-glycan branching of this subunit is important
for intercellular adhesion. The N-glycans of the Na,K-ATPase {beta}1
subunit and E-cadherin are less complex in tight renal epithelia
than in the leakier intestinal epithelium. The complexity of the
N-glycans linked to these proteins gradually decreases upon the formation
of a tight monolayer from dispersed MDCK cells. This correlates with
a cell-cell adhesion-induced increase in expression of GnT-III (stops
N-glycan branching) and a decrease in expression of GnTs IVC and
V (promote N-glycan branching) as detected by real-time quantitative
PCR. Consistent with these results, partial silencing of the gene
encoding GnT-III increases branching of N-glycans linked to the Na,K-ATPase
{beta}1 subunit and other glycoproteins and results in a 2-fold increase
in the paracellular permeability of MDCK cell monolayers. These results
suggest epithelial cells can regulate tightness of cell junctions
via remodeling of N-glycans, including those linked to the Na,K-ATPase
{beta}1-subunit.},
url = {http://www.jbc.org/cgi/content/abstract/283/4/2192}
}
@ARTICLE{Vaishnav2008,
author = {Vaishnav, Radhika A. and Getchell, Marilyn L. and Huang, Liping and
Hersh, Matthew A. and Stromberg, Arnold J. and Getchell, Thomas V.},
title = {Cellular and molecular characterization of oxidative stress in olfactory
epithelium of Harlequin mutant mouse},
journal = {J. Neurosci. Res.},
year = {2008},
volume = {86},
pages = {165--182},
number = {1},
abstract = {Abstract 10.1002/jnr.21464.abs Oxidative stress in the olfactory system
is a major factor associated with age-related olfactory impairment,
although the mechanisms by which this occurs are not completely understood.
The Harlequin mutant mouse (Hq/Y), which carries an X-linked recessive
mutation in the Aifm1 gene, is a model of progressive oxidative stress–induced
neurodegeneration in the cerebellum and retina. To determine whether
the Hq/Y mutant mouse is a suitable model of oxidative stress–associated
olfactory aging, we investigated cellular and molecular changes in
the olfactory epithelium (OE) and olfactory bulb (OB) of 6-month-old
male Hq/Y mice compared to those in sex-matched littermate controls
(+/Y) and in age- and sex-matched C57BL/6 mice. Immunoreactivity
for apoptosis-inducing factor, the protein product of Aifm1, was
localized in mature olfactory sensory neurons (mOSNs) in +/Y mice
but was rarely detected in Hq/Y mice. Hq/Y mice also exhibited increased
lipofuscin autofluorescence and increased immunoreactivity for an
oxidative DNA/RNA damage marker in mOSNs and in mitral/tufted cells
in the OB and an increased number of cleaved caspase-3 immunoreactive
apoptotic cells in the OE. Microarray analysis demonstrated that
Aifm1 expression was down-regulated by 80% in the OE of Hq/Y mice
compared to that in +/Y mice. Most significantly, regulated genes
were classified into functional categories of cell signaling/apoptosis/cell
cycle, oxidative stress/aging, and cytoskeleton/extracellular matrix/transport-associated.
Analysis with EASE software indicated that the functional categories
significantly overrepresented in Hq/Y mice included up-regulated
mitochondrial genes and down-regulated cytoskeletal organization-
and neurogenesis-related genes. Our results strongly support the
Hq/Y mutant mouse being a novel model for mechanistic studies of
oxidative stress–associated olfactory aging. © 2007 Wiley-Liss,
Inc.},
issn = {1097-4547},
keywords = {apoptosis-inducing factor, Aifm1, 8-hydro-xydeoxyguanosine/8-hydroxyguanosine,
mitochondria, bioinformatics},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.21464}
}
@ARTICLE{Vaithilingam2011,
author = {Vijayaganapathy Vaithilingam and Nayeem Quayum and Mugdha V. Joglekar
and Jan Jensen and Anandwardhan A. Hardikar and Jose Oberholzer and
Gilles J. Guillemin and Bernard E. Tuch},
title = {Effect of alginate encapsulation on the cellular transcriptome of
human islets},
journal = {Biomaterials},
year = {2011},
volume = {32},
pages = {8416 - 8425},
number = {33},
abstract = {Encapsulation of human islets may prevent their immune rejection when
transplanted into diabetic recipients. To assist in understanding
why clinical outcomes with encapsulated islets were not ideal, we
examined the effect of encapsulation on their global gene (mRNA)
and selected miRNAs (non-coding (nc)RNA) expression. For functional
studies, encapsulated islets were transplanted into peritoneal cavity
of diabetic NOD-SCID mice. Genomics analysis and transplantation
studies demonstrate that islet origin and isolation centres are a
major source of variation in islet quality. In contrast, tissue culture
and the encapsulation process had only a minimal effect, and did
not affect islet viability. Microarray analysis showed that as few
as 29 genes were up-regulated and 2 genes down-regulated (cut-off
threshold 0.1) by encapsulation. Ingenuity analysis showed that up-regulated
genes were involved mostly in inflammation, especially chemotaxis,
and vascularisation. However, protein expression of these factors
was not altered by encapsulation, raising doubts about the biosignificance
of the gene changes. Encapsulation had no effect on levels of islet
miRNAs. In vivo studies indicate differences among the centres in
the quality of the islets isolated. We conclude that microencapsulation
of human islets with barium alginate has little effect on their transcriptome.},
doi = {10.1016/j.biomaterials.2011.06.044},
issn = {0142-9612},
keywords = {Cell encapsulation},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211007095}
}
@ARTICLE{Vaksman2011,
author = {Vaksman, Olga and Stavnes, Helene Tuft and Kærn, Janne and Trope,
Claes G. and Davidson, Ben and Reich, Reuven},
title = {miRNA profiling along tumour progression in ovarian carcinoma},
journal = {Journal of Cellular and Molecular Medicine},
year = {2011},
volume = {15},
pages = {1593--1602},
number = {7},
abstract = {MicroRNAs (miRNAs) are small non-coding RNAs that exert a regulatory
effect post-transcriptionally by binding target mRNAs and inhibiting
gene translation. miRNA expression is deregulated in cancer. The
aim of this study was to characterize the differences in miRNA expression
pattern and the miRNA-regulating machinery between ovarian carcinoma
(OC) cells in primary tumours versus effusions. Using miRNA array
platforms, we analysed a set of 21 tumours (13 effusions, 8 primary
carcinomas) and identified three sets of miRNAs, one that is highly
expressed in both primary carcinomas and effusions, one overexpressed
in primary carcinomas and one overexpressed in effusions. Levels
of selected miRNAs were analysed using quantitative PCR in an independent
set of 45 additional tumours (30 effusions, 15 primary carcinomas).
Reduced miR-145 and miR-214 and elevated let-7f, miR-182, miR-210,
miR-200c, miR-222 and miR-23a levels were found in effusions in both
sets. In silico target prediction programs identified potential target
genes for some of the differentially expressed miRNAs. Expression
of zinc finger E-box binding homeobox (ZEB)1 and c-Myc, targets of
miR-200c, as well as of p21 protein (Cdc42/Rac)-activated kinase
(PAK)1 and phosphatase and tensin homologue deleted on chromosome
10 (PTEN), predicted targets of miR-222, were analysed. Inverse correlations
between expression levels of the indicated miRNAs and of the predicted
target genes were found. In addition, higher expression of the miRNA-processing
molecules Ago1, Ago2 and Dicer was observed in effusions compared
to primary carcinomas. In conclusion, our data are the first to document
different miRNA expression and regulation profiles in primary and
metastatic OC, suggesting a role for these molecules in tumour progression.},
doi = {10.1111/j.1582-4934.2010.01148.x},
issn = {1582-4934},
keywords = {miRNA profiling, ovarian carcinoma, tumour progression, effusions},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2010.01148.x}
}
@ARTICLE{Valarmathi2009,
author = {Valarmathi, Mani T. and Davis, Jeffrey M. and Yost, Michael J. and
Goodwin, Richard L. and Potts, Jay D.},
title = {A three-dimensional model of vasculogenesis},
journal = {Biomaterials},
year = {2009},
volume = {30},
pages = {1098--1112},
number = {6},
month = feb,
abstract = {Postnatal bone marrow contains various subpopulations of resident
and circulating stem cells (HSCs, BMSCs/MSCs) and progenitor cells
(MAPCs, EPCs) that are capable of differentiating into one or more
of the cellular components of the vascular bed in vitro as well as
contribute to postnatal neo-vascularization in vivo. When rat BMSCs
were seeded onto a three-dimensional (3-D) tubular scaffold engineered
from topographically aligned type I collagen fibers and cultured
either in vasculogenic or non-vasculogenic media for 7, 14, 21 or
28 days, the maturation and co-differentiation into endothelial and/or
smooth muscle cell lineages were observed. Phenotypic induction of
these substrate-grown cells was assayed at transcript level by real-time
PCR and at protein level by confocal microscopy. In the present study,
the observed upregulation of transcripts coding for vascular phenotypic
markers is reminiscent of an in vivo expression pattern. Immunolocalization
of vasculogenic lineage-associated markers revealed typical expression
patterns of vascular endothelial and smooth muscle cells. These endothelial
cells exhibited high metabolism of acetylated low-density lipoprotein.
In addition to the induced monolayers of endothelial cells, the presence
of numerous microvascular capillary-like structures was observed
throughout the construct. At the level of scanning electron microscopy,
smooth-walled cylindrical tube-like structures with smooth muscle
cells and/or pericytes attached to its surface were elucidated. Our
3-D culture system not only induces the maturation and differentiation
of BMSCs into vascular cell lineages but also supports microvessel
morphogenesis. Thus, this unique in vitro model provides an excellent
platform to study the temporal and spatial regulation of postnatal
de novo vasculogenesis, as well as attack the lingering limit in
developing engineered tissues, that is perfusion.},
issn = {0142-9612},
keywords = {Bone marrow stromal cells, Mesenchymal stem cells, Vasculogenesis,
Angiogenesis, Vascular tissue engineering},
url = {http://www.sciencedirect.com/science/article/B6TWB-4V053G0-9/2/cdd7cac9da8fcab8d83d3e3e0bd98dce}
}
@ARTICLE{Valarmathi2011,
author = {Valarmathi, Mani T. and Fuseler, John W. and Goodwin, Richard L.
and Davis, Jeffrey M. and Potts, Jay D.},
title = {The mechanical coupling of adult marrow stromal stem cells during
cardiac regeneration assessed in a 2-D co-culture model},
journal = {Biomaterials},
year = {2011},
volume = {32},
pages = {2834--2850},
number = {11},
month = apr,
abstract = {Postnatal cardiomyocytes undergo terminal differentiation and a restricted
number of human cardiomyocytes retain the ability to divide and regenerate
in response to ischemic injury. However, whether these neo-cardiomyocytes
are derived from endogenous population of resident cardiac stem cells
or from the exogenous double assurance population of resident bone
marrow-derived stem cells that populate the damaged myocardium is
unresolved and under intense investigation. The vital challenge is
to ameliorate and/or regenerate the damaged myocardium. This can
be achieved by stimulating proliferation of native quiescent cardiomyocytes
and/or cardiac stem cell, or by recruiting exogenous autologous or
allogeneic cells such as fetal or embryonic cardiomyocyte progenitors
or bone marrow-derived stromal stem cells. The prerequisites are
that these neo-cardiomyocytes must have the ability to integrate
well within the native myocardium and must exhibit functional synchronization.
Adult bone marrow stromal cells (BMSCs) have been shown to differentiate
into cardiomyocyte-like cells both in vitro and in vivo. As a result,
BMSCs may potentially play an essential role in cardiac repair and
regeneration, but this concept requires further validation. In this
report, we have provided compelling evidence that functioning cardiac
tissue can be generated by the interaction of multipotent BMSCs with
embryonic cardiac myocytes (ECMs) in two-dimensional (2-D) co-cultures.
The differentiating BMSCs were induced to undergo cardiomyogenic
differentiation pathway and were able to express unequivocal electromechanical
coupling and functional synchronization with ECMs. Our 2-D co-culture
system provides a useful in vitro model to elucidate various molecular
mechanisms underpinning the integration and orderly maturation and
differentiation of BMSCs into neo-cardiomyocytes during myocardial
repair and regeneration.},
issn = {0142-9612},
keywords = {Bone marrow stromal cells, Mesenchymal stem cells, Embryonic cardiac
myocytes, Dedifferentiation, Myocardial regeneration, Cardiac tissue
engineering},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211000135}
}
@ARTICLE{Valarmathi2010,
author = {Valarmathi, Mani T. and Goodwin, Richard L. and Fuseler, John W.
and Davis, Jeffrey M. and Yost, Michael J. and Potts, Jay D.},
title = {A 3-D cardiac muscle construct for exploring adult marrow stem cell
based myocardial regeneration},
journal = {Biomaterials},
year = {2010},
volume = {31},
pages = {3185--3200},
number = {12},
month = apr,
abstract = {Adult bone marrow stromal cells (BMSCs) are capable of differentiating
into cardiomyocyte-like cells in vitro and contribute to myocardial
regeneration in vivo. Consequently, BMSCs may potentially play a
vital role in cardiac repair and regeneration. However, this concept
has been limited by inadequate and inconsistent differentiation of
BMSCs into cardiomyocytes along with poor survival and integration
of neo-cardiomyocytes after implantation into ischemic myocardium.
In order to overcome these barriers and to explore adult stem cell
based myocardial regeneration, we have developed an in vitro model
of three-dimensional (3-D) cardiac muscle using rat ventricular embryonic
cardiomyocytes (ECMs) and BMSCs. When ECMs and BMSCs were seeded
sequentially onto a 3-D tubular scaffold engineered from topographically
aligned type I collagen-fibers and cultured in basal medium for 7,
14, 21, or 28 days, the maturation and co-differentiation into a
cardiomyocyte lineage was observed. Phenotypic induction was characterized
at morphological, immunological, biochemical and molecular levels.
The observed expression of transcripts coding for cardiomyocyte phenotypic
markers and the immunolocalization of cardiomyogenic lineage-associated
proteins revealed typical expression patterns of neo-cardiomyogenesis.
At the biochemical level differentiating cells exhibited appropriate
metabolic activity and at the ultrastructural level myofibrillar
and sarcomeric organization were indicative of an immature phenotype.
Our 3-D co-culture system sustains the ECMs in vitro continuum of
differentiation process and simultaneously induces the maturation
and differentiation of BMSCs into cardiomyocyte-like cells. Thus,
this novel 3-D co-culture system provides a useful in vitro model
to investigate the functional role and interplay of developing ECMs
and BMSCs during cardiomyogenic differentiation.},
issn = {0142-9612},
keywords = {Bone marrow stromal cells, Mesenchymal stem cells, Embryonic cardiac
myocytes, Myocardial regeneration, Cardiac tissue engineering},
url = {http://www.sciencedirect.com/science/article/B6TWB-4Y9C194-4/2/ef3eea811906dc2228011f5f0f3ba359}
}
@ARTICLE{Valarmathi2008,
author = {Valarmathi, Mani T. and Yost, Michael J. and Goodwin, Richard L.
and Potts, Jay D.},
title = {The influence of proepicardial cells on the osteogenic potential
of marrow stromal cells in a three-dimensional tubular scaffold},
journal = {Biomaterials},
year = {2008},
volume = {29},
pages = {2203--2216},
number = {14},
month = may,
abstract = {It is well established that the process of neovascularization or neoangiogenesis
is coupled to the development and maturation of bone. Bone marrow
stromal cells (BMSCs) or mesenchymal stem cells (MSCs) comprise a
heterogeneous population of cells that can be differentiated in vitro
into both mesenchymal and non-mesenchymal cell lineages. When both
rat BMSCs and quail proepicardia (PEs) were seeded onto a three-dimensional
(3-D) tubular scaffold engineered from aligned collagen type I strands
and co-cultured in osteogenic media, the maturation and co-differentiation
into osteoblastic and vascular cell lineages were observed. In addition,
these cells produced abundant mineralized extracellular matrix materials
and vessel-like structures. BMSCs were seeded at a density of 2 × 106 cells/15 mm
tube and cultured in basal media for 3 days. Subsequently, on day
3, PEs were seeded onto the same tubes and the co-culture was continued
for another 3, 6 or 9 days either in basal or in osteogenic media.
Differentiated cells were subjected to immunohistochemical, cytochemical
and biochemical analyses. Phenotypic induction was analyzed at mRNA
level by reverse transcriptase quantitative polymerase chain reaction
(RT-qPCR). Immunolocalization of key osteogenic and vasculogenic
lineage specific markers were examined using confocal scanning laser
microscopy. In osteogenic tube cultures, both early and late osteogenic
markers were observed and were reminiscent of in vivo expression
pattern. Alkaline phosphatase activity and calcium content significantly
increased over the observed period of time in osteogenic medium.
Abundant interlacing fascicles of QCPN, QH1, isolectin and [alpha]-smooth
muscle actin ([alpha]-SMA) positive cells were observed in these
tube cultures. These cells formed extensive arborizations of nascent
capillary-like structures and were seen amidst the developing osteoblasts
in osteogenic cultures. The 3-D culture system not only generated
de novo vessel-like structures but also augmented the maturation
and differentiation of BMSCs into osteoblasts. Thus, this novel co-culture
system provides a useful in vitro model to investigate the functional
role and effects of neovascularization in the proliferation, differentiation
and maturation of BMSC derived osteoblasts.},
issn = {0142-9612},
keywords = {Bone marrow stromal cells, Mesenchymal stem cells, Proepicardial cells,
Osteogenesis, Vasculogenesis, Bone tissue engineering},
url = {http://www.sciencedirect.com/science/article/B6TWB-4S0B2PN-4/2/1b998d3f0c1a59ab6b1f66a692862647}
}
@ARTICLE{Valastyan2008,
author = {Valastyan, Scott and Thakur, Varsha and Johnson, Amy and Kumar, Karan
and Manor, Danny},
title = {Novel Transcriptional Activities of Vitamin E: Inhibition of Cholesterol
Biosynthesis†},
journal = {Biochemistry},
year = {2008},
volume = {47},
pages = {744-752},
number = {2},
note = {PMID: 18095660},
doi = {10.1021/bi701432q},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi701432q},
url = {http://pubs.acs.org/doi/abs/10.1021/bi701432q}
}
@ARTICLE{Valdes2012,
author = {Valdés, Ana Elisa And Rizzardi, Kristina And Johannesson, Henrik
And Para, Alessia And Sundås-larsson, Annika And Landberg, Katarina},
title = {Arabidopsis thaliana TERMINAL FLOWER2 is involved in light-controlled
signalling during seedling photomorphogenesis},
journal = {Plant, Cell \& Environment},
year = {2012},
volume = {na},
pages = {no--no},
abstract = {Plants respond to changes in the environment by altering their growth
pattern. Light is one of the most important environmental cues and
affects plants throughout the life cycle. It is perceived by photoreceptors
such as phytochromes that absorb light of red and far-red wavelengths
and control, for example, seedling de-etiolation, chlorophyll biosynthesis
and shade avoidance response. We report that the terminal flower2
(tfl2) mutant, carrying a mutation in the Arabidopsis thaliana HETEROCHROMATIN
PROTEIN1 homolog, functions in negative regulation of phytochrome
dependent light signalling. tfl2 shows defects in both hypocotyl
elongation and shade avoidance response. Double mutant analysis indicates
that mutants of the red/far-red light absorbing phytochrome family
of plant photoreceptors, phyA and phyB, are epistatic to tfl2 in
far-red and red light, respectively. An overlap between genes regulated
by light and by auxin has earlier been reported and, in tfl2 plants
light-dependent auxin-regulated genes are misexpressed. Further,
we show that TFL2 binds to IAA5 and IAA19 suggesting that TFL2 might
be involved in regulation of phytochrome-mediated light responses
through auxin action.},
doi = {10.1111/j.1365-3040.2011.02468.x},
issn = {1365-3040},
keywords = {auxin, LIKE HETEROCHROMATIN PROTEIN1, phytochrome, shade avoidance
response},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3040.2011.02468.x}
}
@ARTICLE{Valen2011,
author = {Valen, R. and Jordal, A.-E.O. and Murashita, K. and Rønnestad, I.},
title = {Postprandial effects on appetite-related neuropeptide expression
in the brain of Atlantic salmon, Salmo salar},
journal = {General and Comparative Endocrinology},
year = {2011},
volume = {171},
pages = {359--366},
number = {3},
month = may,
abstract = {Following feeding of a single meal to Atlantic salmon, the temporal
changes in the brain mRNA expression of neuropeptide y (npy), cocaine-amphetamine
regulated transcript (cart), peptide yy (pyy), two isoforms of agouti-related
protein (agrp), two isoforms of cholecystokinin (cck), and four isoforms
of proopiomelanocortin (pomc) were assessed by q-PCR. In the course
of 24 h post-feeding (hpf), several of the brain neuropeptides displayed
changes in mRNA expression compared to an unfed control group, indicating
that food intake and processing affect the regulation of expression
of these genes in Atlantic salmon. Expression of cart, cck-l, pomc-a1
and pomc-b all increased within 3 h of feeding, while most of the
feed was still in the stomach, suggesting that these neuropeptides
play central anorexigenic roles similar to those described in higher
vertebrates, including determining meal intervals. On the other hand,
the npy and agrp isoforms which have been described as playing orexigenic
roles in mammals, showed an opposite response in salmon and both
were elevated in the first 3 h after feeding. The different isoforms
of cck, agrp and pomc had different mRNA expression patterns, which
indicate specific roles related to feeding regulation. The minimal
effect of feeding and digestion on pyy expression in the brain indicates
that PYY plays a minor role in the central control of short-term
food intake in Atlantic salmon.},
issn = {0016-6480},
keywords = {cart, npy, pyy, cck, agrp, pomc, Isoforms, Teleost, Appetite, Neuropeptide},
url = {http://www.sciencedirect.com/science/article/pii/S0016648011000773}
}
@ARTICLE{Valencia2006,
author = {Valencia, Julio C. and Watabe, Hidenori and Chi, An and Rouzaud,
Francois and Chen, Kevin G. and Vieira, Wilfred D. and Takahashi,
Kaoruko and Yamaguchi, Yuji and Berens, Werner and Nagashima, Kunio
and Shabanowitz, Jeffrey and Hunt, Donald F. and Appella, Ettore
and Hearing, Vincent J.},
title = {Sorting of Pmel17 to melanosomes through the plasma membrane by AP1
and AP2: evidence for the polarized nature of melanocytes},
journal = {J. Cell Sci.},
year = {2006},
volume = {119},
pages = {1080--1091},
number = {6},
month = mar,
abstract = {Adaptor proteins (AP) play important roles in the sorting of proteins
from the trans-Golgi network, but how they function in the sorting
of various melanosome-specific proteins such as Pmel17, an essential
structural component of melanosomes, in melanocytes is unknown. We
characterized the processing and trafficking of Pmel17 via adaptor
protein complexes within melanocytic cells. Proteomics analysis detected
Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time
PCR, immunolabeling and tissue in-situ hybridization confirmed the
coexpression of AP1 isoforms {micro}1A and {micro}1B (expressed only
in polarized cells) in melanocytes and keratinocytes, but expression
of {micro}1B is missing in some melanoma cell lines. Transfection
with AP1 isoforms ({micro}1A or {micro}1B) showed two distinct distribution
patterns that involved Pmel17, and only {micro}1B was able to restore
the sorting of Pmel17 to the plasma membrane in cells lacking {micro}1B
expression. Finally, we established that expression of {micro}1B
is regulated physiologically in melanocytes by UV radiation or DKK1.
These results show that Pmel17 is sorted to melanosomes by various
intracellular routes, directly or indirectly through the plasma membrane,
and the presence of basolateral elements in melanocytes suggests
their polarized nature.},
url = {http://jcs.biologists.org/cgi/content/abstract/119/6/1080}
}
@ARTICLE{Valente2012,
author = {Anthony J. Valente and Tadashi Yoshida and Jason D. Gardner and Naveen
Somanna and Patrice Delafontaine and Bysani Chandrasekar},
title = {Interleukin-17A stimulates cardiac fibroblast proliferation and migration
via negative regulation of the dual-specificity phosphatase MKP-1/DUSP-1},
journal = {Cellular Signalling},
year = {2012},
volume = {24},
pages = {560 - 568},
number = {2},
abstract = {The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1
(MKP-1) inactivates MAP kinases by dephosphorylation. Here we show
that the proinflammatory cytokine interleukin (IL)-17A induces adult
mouse primary cardiac fibroblast (CF) proliferation and migration
via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression,
and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and
ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged
by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt,
and miR-101 inhibitor reversed MKP-1 down regulation. Importantly,
MKP-1 knockdown, pharmacological inhibition of p38 MAPK and ERK1/2,
or overexpression of dominant negative MEK1, each markedly attenuated
IL-17A-mediated CF proliferation and migration. Similarly, IL-17F
and IL-17A/F heterodimer that also signal via IL-17RA/IL-17RC, stimulated
CF proliferation and migration. These results indicate that IL-17A
stimulates CF proliferation and migration via Akt/miR-101/MKP-1-dependent
p38 MAPK and ERK1/2 activation. These studies support a potential
role for IL-17 in cardiac fibrosis and adverse myocardial remodeling.},
doi = {10.1016/j.cellsig.2011.10.010},
issn = {0898-6568},
keywords = {Cytokines},
url = {http://www.sciencedirect.com/science/article/pii/S089865681100338X}
}
@ARTICLE{Valera2011,
author = {Maria José Valera and Federico Laich and Sara S. González and Maria
Jesús Torija and Estibaliz Mateo and Albert Mas},
title = {Diversity of acetic acid bacteria present in healthy grapes from
the Canary Islands},
journal = {International Journal of Food Microbiology},
year = {2011},
volume = {151},
pages = {105 - 112},
number = {1},
abstract = {The identification of acetic acid bacteria (AAB) from sound grapes
from the Canary Islands is reported in the present study. No direct
recovery of bacteria was possible in the most commonly used medium,
so microvinifications were performed on grapes from Tenerife, La
Palma and Lanzarote islands. Up to 396 AAB were isolated from those
microvinifications and identified by 16S rRNA gene sequencing and
phylogenetic analysis. With this method, Acetobacter pasteurianus,
Acetobacter tropicalis, Gluconobacter japonicus and Gluconacetobacter
saccharivorans were identified.
However, no discrimination between the closely related species Acetobacter
malorum and Acetobacter cerevisiae was possible. As previously described,
16S-23S rRNA gene internal transcribed spacer (ITS) region phylogenetic
analysis was required to classify isolates as one of those species.
These two species were the most frequently occurring, accounting
for more than 60% of the isolates. For typing the AAB isolates, both
the Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR and
(GTG)5-PCR techniques gave similar resolution. A total of 60 profiles
were identified. Thirteen of these profiles were found in more than
one vineyard, and only one profile was found on two different islands
(Tenerife and La Palma).},
doi = {10.1016/j.ijfoodmicro.2011.08.007},
issn = {0168-1605},
keywords = {Wine},
url = {http://www.sciencedirect.com/science/article/pii/S0168160511004661}
}
@ARTICLE{Valeron2009,
author = {Valerón, Pilar F. and Pestano, José J. and Luzardo, Octavio P. and
Zumbado, Manuel L. and Almeida, Maira and Boada, Luis D.},
title = {Differential effects exerted on human mammary epithelial cells by
environmentally relevant organochlorine pesticides either individually
or in combination},
journal = {Chemico-Biological Interactions},
year = {2009},
volume = {180},
pages = {485--491},
number = {3},
month = aug,
abstract = {Organochlorine pesticides (OCs) have been associated with breast cancer
development and progression. However, the deleterious mechanisms
exerted by these contaminants are yet unclear and need to be further
elucidated. In the present study, we investigated the effects of
a number of OCs (previously detected in human serum from a Spanish
population), individually or in combination, on normal human mammary
epithelial cells (HMEC) at concentrations close to those found in
human beings. The results obtained after a 96-h exposure indicated
that OCs exert a clear cytotoxic effect on these cells at higher
concentrations than those found in human beings. DDT-derivative organochlorines
(DDT and its metabolites, DDE and DDD) are individually more cytotoxic
than non-DDT-derivative organochlorines (aldrin and dieldrin). On
the contrary, combinations of non-DDT organochlorines were clearly
more cytotoxic than combinations of DDT-derivative organochlorines
at concentrations close to those described in human serum. Additionally,
transcriptional regulation arrays showed that the exposure of HMEC
to an environmentally relevant mixture of OCs (p,p'-DDD plus p,p'-DDE
plus o,p'-DDE plus aldrin plus dieldrin) sharply upregulated the
expression of a number of protein kinases genes, such as ACVRL1,
ALK-1, KIT, ERBB3, and ALK-1 at concentrations close to those detected
in human populations. Taken together, these findings show a detrimental
effect of OCs on human breast cells and indicate a possible association
between exposure to organochlorine pesticide combinations and the
induction of transformation processes in human breast cells.},
issn = {0009-2797},
keywords = {Organochlorine pesticides (o,p'-DDT, p,p'-DDT, o,p'-DDE, p,p'-DDE,
p,p'-DDD, aldrin and dieldrin), Protein kinases (ACVRL-1, ACVR1C,
PDGFRA, KIT, ERBB3 and ALK-1), Normal human mammary epithelial cells
(HMEC)},
url = {http://www.sciencedirect.com/science/article/B6T56-4W74229-1/2/3776ba16b0f82caef325bcca5bb4c35f}
}
@ARTICLE{Valk2004,
author = {Valk, Peter J.M. and Verhaak, Roel G.W. and Beijen, M. Antoinette
and Erpelinck, Claudia A.J. and van Doorn-Khosrovani, Sahar Barjesteh
van Waalwijk and Boer, Judith M. and Beverloo, H. Berna and Moorhouse,
Michael J. and van der Spek, Peter J. and Lowenberg, Bob and Delwel,
Ruud},
title = {Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia},
journal = {N. Engl. J. Med.},
year = {2004},
volume = {350},
pages = {1617--1628},
number = {16},
month = apr,
abstract = {Background In patients with acute myeloid leukemia (AML) a combination
of methods must be used to classify the disease, make therapeutic
decisions, and determine the prognosis. However, this combined approach
provides correct therapeutic and prognostic information in only 50
percent of cases. Methods We determined the gene-expression profiles
in samples of peripheral blood or bone marrow from 285 patients with
AML using Affymetrix U133A GeneChips containing approximately 13,000
unique genes or expression-signature tags. Data analyses were carried
out with Omniviz, significance analysis of microarrays, and prediction
analysis of microarrays software. Statistical analyses were performed
to determine the prognostic significance of cases of AML with specific
molecular signatures. Results Unsupervised cluster analyses identified
16 groups of patients with AML on the basis of molecular signatures.
We identified the genes that defined these clusters and determined
the minimal numbers of genes needed to identify prognostically important
clusters with a high degree of accuracy. The clustering was driven
by the presence of chromosomal lesions (e.g., t(8;21), t(15;17),
and inv(16)), particular genetic mutations (CEBPA), and abnormal
oncogene expression (EVI1). We identified several novel clusters,
some consisting of specimens with normal karyotypes. A unique cluster
with a distinctive gene-expression signature included cases of AML
with a poor treatment outcome. Conclusions Gene-expression profiling
allows a comprehensive classification of AML that includes previously
identified genetically defined subgroups and a novel cluster with
an adverse prognosis.},
url = {http://content.nejm.org/cgi/content/abstract/350/16/1617}
}
@ARTICLE{Vallanat2010,
author = {Vallanat, Beena and Anderson, Steven and Brown-Borg, Holly and Ren,
Hongzu and Kersten, Sander and Jonnalagadda, Sudhakar and Srinivasan,
Rajagopalan and Corton, J Christopher},
title = {Analysis of the heat shock response in mouse liver reveals transcriptional
dependence on the nuclear receptor peroxisome proliferator-activated
receptor a (PPARa)},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {16},
number = {1},
abstract = {BACKGROUND:The nuclear receptor peroxisome proliferator-activated
receptor alpha (PPARa) regulates responses to chemical or physical
stress in part by altering expression of genes involved in proteome
maintenance. Many of these genes are also transcriptionally regulated
by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized
that there are interactions on a genetic level between PPARa and
the HS response mediated by HSF1.RESULTS:Wild-type and PPARa-null
mice were exposed to HS, the PPARa agonist WY-14,643 (WY), or both;
gene and protein expression was examined in the livers of the mice
4 or 24 hrs after HS. Gene expression profiling identified a number
of Hsp family members that were altered similarly in both mouse strains.
However, most of the targets of HS did not overlap between strains.
A subset of genes was shown by microarray and RT-PCR to be regulated
by HS in a PPARa-dependent manner. HS also down-regulated a large
set of mitochondrial genes specifically in PPARa-null mice that are
known targets of PPAR? co-activator-1 (PGC-1) family members. Pretreatment
of PPARa-null mice with WY increased expression of PGC-1ß and target
genes and prevented the down-regulation of the mitochondrial genes
by HS. A comparison of HS genes regulated in our dataset with those
identified in wild-type and HSF1-null mouse embryonic fibroblasts
indicated that although many HS genes are regulated independently
of both PPARa and HSF1, a number require both factors for HS responsiveness.CONCLUSIONS:These
findings demonstrate that the PPARa genotype has a dramatic effect
on the transcriptional targets of HS and support an expanded role
for PPARa in the regulation of proteome maintenance genes after exposure
to diverse forms of environmental stress including HS.},
doi = {10.1186/1471-2164-11-16},
issn = {1471-2164},
pubmedid = {20059764},
url = {http://www.biomedcentral.com/1471-2164/11/16}
}
@ARTICLE{Vallania2009,
author = {Vallania, Francesco and Schiavone, Davide and Dewilde, Sarah and
Pupo, Emanuela and Garbay, Serge and Calogero, Raffaele and Pontoglio,
Marco and Provero, Paolo and Poli, Valeria},
title = {Genome-wide discovery of functional transcription factor binding
sites by comparative genomics: The case of Stat3},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {5117--5122},
number = {13},
month = mar,
abstract = {The identification of direct targets of transcription factors is a
key problem in the study of gene regulatory networks. However, the
use of high throughput experimental methods, such as ChIP-chip and
ChIP-sequencing, is limited by their high cost and strong dependence
on cellular type and context. We developed a computational method
for the genome-wide identification of functional transcription factor
binding sites based on positional weight matrices, comparative genomics,
and gene expression profiling. The method was applied to Stat3, a
transcription factor playing crucial roles in inflammation, immunity
and oncogenesis, and able to induce distinct subsets of target genes
in different cell types or conditions. A newly generated positional
weight matrix enabled us to assign affinity scores of high specificity,
as measured by EMSA competition assays. Phylogenetic conservation
with 7 vertebrate species was used to select the binding sites most
likely to be functional. Validation was carried out on predicted
sites within genes identified as differentially expressed in the
presence or absence of Stat3 by microarray analysis. Twelve of the
fourteen sites tested were bound by Stat3 in vivo, as assessed by
Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional
targets. Given its high validation rate, and the availability of
large transcription factor-dependent gene expression datasets obtained
under diverse experimental conditions, our approach appears to be
a valid alternative to high-throughput experimental assays for the
discovery of novel direct targets of transcription factors.},
url = {http://www.pnas.org/cgi/content/abstract/106/13/5117}
}
@ARTICLE{Vallat2007,
author = {Vallat, Laurent D. and Park, Yuhyun and Li, Cheng and Gribben, John
G.},
title = {Temporal genetic program following B-cell receptor cross-linking:
altered balance between proliferation and death in healthy and malignant
B cells},
journal = {Blood},
year = {2007},
volume = {109},
pages = {3989--3997},
number = {9},
month = may,
abstract = {Gene expression in cells is a dynamic process but is usually examined
at a single time point. We used gene expression profiling over time
to build temporal models of gene transcription after B-cell receptor
(BCR) signaling in healthy and malignant B cells and chose this as
a model since BCR cross-linking induces both cell proliferation and
apoptosis, with increased apoptosis in chronic lymphocytic leukemia
(CLL) compared to healthy B cells. To determine the basis for this,
we examined the global temporal gene expression profile for BCR stimulation
and developed a linear combination method to summarize the effect
of BCR simulation over all the time points for all patients. Functional
learning identified common early events in healthy B cells and CLL
cells. Although healthy and malignant B cells share a common genetic
pattern early after BCR signaling, a specific genetic program is
engaged by the malignant cells at later time points after BCR stimulation.
These findings identify the molecular basis for the different functional
consequences of BCR cross-linking in healthy and malignant B cells.
Analysis of gene expression profiling over time may be used to identify
genes that might be rational targets to perturb these pathways.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/9/3989}
}
@ARTICLE{Vallee2008,
author = {Vallee, Maud and Aiba, Kazuhiro and Piao, Yulan and Palin, Marie-France
and Ko, Minoru S H and Sirard, Marc-Andre},
title = {Comparative analysis of oocyte transcript profiles reveals a high
degree of conservation among species},
journal = {Reproduction},
year = {2008},
volume = {135},
pages = {439--448},
number = {4},
month = apr,
abstract = {Cross-species comparison of gene expression is a powerful approach
for discovering genes that have been conserved throughout evolution.
Conserved genes are presumably very important in the mechanisms related
to the unique molecular functions in oocytes. The objective of this
study was to identify genes expressed in the oocyte and conserved
across three diverse vertebrate species. We report the global gene
expression profiles of Bos taurus and Xenopus laevis oocytes on an
NIA mouse development microarray that consists of 60-mer oligonucleotide
probes representing more than 20 000 mouse transcripts derived from
stem cell, oocyte, and early embryo cDNA libraries. Analysis based
on intensity values revealed that 9853 and 10 046 genes are expressed
in bovine and Xenopus oocytes respectively. Furthermore, previously
published microarray data on preimplantation development in the mouse
were used for a comparative analysis of global oocyte gene expression
profiles. Interestingly, a substantial proportion of the genes expressed
in mouse oocytes is conserved between the three species (74%, 7275
genes). Moreover, functional annotation of these conserved oocyte-expressed
genes confirmed that certain functions are conserved among the three
species. RNA metabolism and cell cycle were among the over-represented
Gene Ontology terms in the biological process category. Finally,
a pattern-matching analysis identified 208 conserved maternally expressed
genes. Results from these cross-species hybridizations allowed numerous
genes expressed in oocytes and conserved between Mus musculus, B.
taurus, and X. laevis to be identified. This comparative analysis
of oocyte transcript profiles revealed a high degree of conservation
among species.},
url = {http://www.reproduction-online.org/cgi/content/abstract/135/4/439}
}
@ARTICLE{Vallelian2010,
author = {Vallelian, Florence and Schaer, Christian A. and Kaempfer, Theresa
and Gehrig, Peter and Duerst, Elena and Schoedon, Gabriele and Schaer,
Dominik J.},
title = {Glucocorticoid treatment skews human monocyte differentiation into
a hemoglobin-clearance phenotype with enhanced heme-iron recycling
and antioxidant capacity},
journal = {Blood},
year = {2010},
volume = {116},
pages = {5347--5356},
number = {24},
month = dec,
abstract = {Glucocorticoids are used extensively to treat autoimmune hemolytic
anemias. Some beneficial effects of glucocorticoid pulse therapy
have also been reported in sickle cell disease and paroxysmal nocturnal
hemoglobinuria. Based on established concepts of hemoglobin (Hb)
toxicity and physiologic Hb scavenger systems, we evaluated whether
glucocorticoids could support an adaptive response to extracellular
Hb independently of their immunosuppressive activities. Using global
proteome and transcriptome analysis with mass-spectrometry (isobaric
tag for relative and absolute quantitation and liquid chromatography-mass
spectrometry) and gene-array experiments, we found that glucocorticoid
treatment in vitro and in patients on glucocorticoid-pulse therapy
polarized monocytes into a M2/alternatively activated phenotype with
high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance
and detoxification capability. Monocytes concurrently exposed to
the interactive activity of glucocorticoids and extracellular Hb
were characterized by high expression of a group of antioxidant enzymes
known to be regulated by the conserved oxidative response transcription
factor nuclear factor E2-related factor. Further, suppressed transferrin
receptor, together with high ferroportin expression, pointed to a
shift in iron homeostasis directed toward an increased cellular export
of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163
and enhancing antioxidative homeostasis and iron recycling may be
an essential activity of glucocorticoids that helps alleviate the
adverse effects of extracellular Hb.},
comment = {10.1182/blood-2010-04-277319},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/116/24/5347}
}
@ARTICLE{Vallender2011,
author = {Vallender, Eric},
title = {Expanding whole exome resequencing into non-human primates},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R87},
number = {9},
abstract = {BACKGROUND:Complete exome resequencing has the power to greatly expand
our understanding of non-human primate genomes. This includes both
a better appreciation of the variation that exists in non-human primate
model species, but also an improved annotation of their genomes.
By developing an understanding of the variation between individuals,
non-human primate models of human disease can be better developed.
This effort is hindered largely by the lack of comprehensive information
on specific non-human primate genetic variation and the costs of
generating these data. If the tools that have been developed in humans
for complete exome resequencing can be applied to closely related
non-human primate species, then these difficulties can be circumvented.RESULTS:Using
a human whole exome enrichment technique, chimpanzee and rhesus macaque
samples were captured alongside a human sample and sequenced using
standard next-generation methodologies. The results from the three
species were then compared for efficacy. The chimpanzee sample showed
similar coverage levels and distributions following exome capture
based on the human genome as the human sample. The rhesus macaque
sample showed significant coverage in protein-coding sequence but
significantly less in untranslated regions. Both chimpanzee and rhesus
macaque showed significant numbers of frameshift mutations compared
to self-genomes and suggest a need for further annotation.CONCLUSIONS:Current
whole exome resequencing technologies can successfully be used to
identify coding-region variation in non-human primates extending
into old world monkeys. In addition to identifying variation, whole
exome resequencing can aid in better annotation of non-human primate
genomes.},
doi = {10.1186/gb-2011-12-9-r87},
issn = {1465-6906},
pubmedid = {21917143},
url = {http://genomebiology.com/2011/12/9/R87}
}
@ARTICLE{Vallender2006,
author = {Vallender, Tammy W. and Lahn, Bruce T.},
title = {Localized methylation in the key regulator gene endothelin-1 is associated
with cell type-specific transcriptional silencing},
journal = {FEBS Letters},
year = {2006},
volume = {580},
pages = {4560--4566},
number = {18},
month = aug,
abstract = {DNA methylation can contribute to the stable transcriptional silencing
of mammalian genes. Often times, these genes are important developmental
regulators, and their silencing in cell types where they are not
supposed to be active is important for the phenotypic stability of
the cells. To identify key developmental regulator genes whose expression
in terminally differentiated cells may be inhibited by DNA methylation,
mouse dermal fibroblasts were demethylated with 5-aza-2'-deoxycytidine,
and changes in gene expression monitored by microarray analysis.
Endothelin-1 (Et1 or Edn1), which encodes a cytokine with diverse
regulatory functions, was among the genes upregulated following demethylation.
We found that CpG dinucleotides within a short region in intron 1
of the gene have dramatically higher levels of methylation in Et1-non-expressing
fibroblasts and chondrocytes as compared to the Et1-expressing mouse
cell line, mIMCD-3. Strong evolutionary conservation of this region
implies its role in the cis-regulation of Et1 transcription. To confirm
that should Et1 in dermal fibroblasts become aberrantly activated,
it could indeed lead to the dysregulation of many downstream genes,
we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional
changes by microarray. ET1 treatment resulted in significant expression
changes - primarily downregulation - of a significant number of genes.
In particular, Tgf[beta]2 and Tgf[beta]3 were among the downregulated
genes, which in turn alter the expression status of their many target
genes. These data suggest that the stable silencing of Et1 through
its associated DNA methylation in intron 1 is critical for the developmental
stability of dermal fibroblasts, and perhaps other cell types as
well.},
issn = {0014-5793},
keywords = {Endothelin-1, Et1, Edn1, DNA methylation, Dermal fibroblast, Tgf[beta]2,
Tgf[beta]3},
url = {http://www.sciencedirect.com/science/article/B6T36-4KDBJ1P-7/2/2da0ee6539cde69d07591b203c1851b9}
}
@ARTICLE{Valles2011,
author = {Valles, Astrid and Boender, Arjen J. and Gijsbers, Steef and Haast,
Roy A. M. and Martens, Gerard J. M. and de Weerd, Peter},
title = {Genomewide Analysis of Rat Barrel Cortex Reveals Time- and Layer-Specific
mRNA Expression Changes Related to Experience-Dependent Plasticity},
journal = {J. Neurosci.},
year = {2011},
volume = {31},
pages = {6140--6158},
number = {16},
month = apr,
abstract = {Because of its anatomical organization, the rodent whisker-to-barrel
system is an ideal model to study experience-dependent plasticity.
Manipulation of sensory input causes changes in the properties of
the barrels at the physiological, structural, and functional levels.
However, much less is known about the molecular events underlying
these changes. To explore such molecular events, we have used a genomewide
approach to identify key genes and molecular pathways involved in
experience-induced plasticity in the barrel cortex of adult rats.
Given the natural tendency of rats to explore novel objects, exposure
to an enriched environment (EE) was used to stimulate the activity
of the whisker-to-barrel cortex in vivo. Microarray analysis at two
different time points after EE revealed differential expression of
genes encoding transcription factors, including nuclear receptors,
as well as of genes involved in the regulation of synaptic plasticity,
cell differentiation, metabolism, and, surprisingly, blood vessel
morphogenesis. These expression differences reflect changes in somatosensory
information processing because unilateral whisker clipping showed
EE-induced differential expression patterns in the spared versus
deprived barrel cortex. Finally, in situ hybridization revealed cortical
layer patterns specific for each selected gene. Together, the present
study offers the first genomewide exploration of the key genes regulated
by somatosensory stimulation in the barrel cortex and thus provides
a solid experimental framework for future in-depth analysis of the
mechanisms underlying experience-dependent plasticity.},
comment = {10.1523/JNEUROSCI.6514-10.2011},
url = {http://www.jneurosci.org/cgi/content/abstract/31/16/6140}
}
@ARTICLE{Vallois2007,
author = {Vallois, David and Grimm, Christina H. and Avner, Philip and Boitard,
Christian and Rogner, Ute Christine},
title = {The Type 1 Diabetes Locus Idd6 Controls TLR1 Expression},
journal = {J. Immunol.},
year = {2007},
volume = {179},
pages = {3896--3903},
number = {6},
month = sep,
abstract = {The Idd6 locus on mouse chromosome 6, which controls the development
of type 1 diabetes in the NOD mouse, affects proliferation rates
of T cells and the activity of regulatory CD4+CD25+ T cells. Using
a transcriptional profiling approach, we show that splenocytes and
thymocytes from diabetes-resistant Idd6 NOD.C3H-congenic mouse strains
exhibit a constitutive and specific down-regulation of Toll-like
receptor 1 (Tlr1) gene expression compared with diabetes prone NOD
mice. This phenotype correlates with a diminished proliferation capacity
of both CD4+CD25- effector and CD4+CD25+ regulatory T cells upon
in vitro stimulation of the TLR1/TLR2 pathway by the ligand palmitoyl-3-cysteine-serine-lysine
4, and with the constitutive down-regulation of Tnf-{alpha} and IL-6
in macrophages of Idd6- congenic mice. These data suggest that TLR1
is involved in the regulation of mechanisms that impinge on diabetes
development in the NOD mouse.},
url = {http://www.jimmunol.org/cgi/content/abstract/179/6/3896}
}
@ARTICLE{Vallons2010,
author = {Vallons, Katleen J.R. and Arendt, Elke K.},
title = {Understanding high pressure-induced changes in wheat flour-water
suspensions using starch-gluten mixtures as model systems},
journal = {Food Research International},
year = {2010},
volume = {43},
pages = {893--901},
number = {3},
month = apr,
issn = {0963-9969},
keywords = {Wheat flour, Wheat starch, Wheat gluten, High pressure, Gelatinisation,
Rheological properties},
url = {http://www.sciencedirect.com/science/article/B6T6V-4Y0KWD2-2/2/bac03bf60d090ca5246ccb643f0b04f0}
}
@ARTICLE{Vallons2011,
author = {Vallons, Katleen J.R. and Ryan, Liam A.M. and Arendt, Elke K.},
title = {Promoting structure formation by high pressure in gluten-free flours},
journal = {LWT - Food Science and Technology},
year = {2011},
volume = {44},
pages = {1672--1680},
number = {7},
month = sep,
abstract = {In order to evaluate the potential of high pressure (HP) treatment
to improve the functional properties of gluten-free flours, the effect
of HP on the rheological properties of three gluten-free batters
was investigated. Buckwheat, white rice and teff batters (40 g/100 g)
were treated for 10 min at 200, 400 or 600 MPa. Changes in the microstructure
of the batters after HP-treatment were observed using scanning electron
microscopy. Pasting profiles revealed HP-induced starch gelatinisation.
Furthermore, Lab-on-a-Chip capillary gel electrophoresis revealed
protein polymerisation by thiol/disulphide-interchange reactions
in white rice and teff batters. For buckwheat proteins however, no
such cross-linking mechanism was observed, which was explained by
the absence of free sulfhydryl groups. An increase in viscoelastic
properties at higher pressures was observed, and could be explained
by the modifications occurring in starch and protein structure. Overall,
this study has shown that HP-treatment has the potential to improve
functional properties of gluten-free batters.},
issn = {0023-6438},
keywords = {Gluten-free, High pressure, Rheological properties, Lab-on-a-chip,
Gelatinisation, Disulphide bonds},
url = {http://www.sciencedirect.com/science/article/pii/S0023643810004019}
}
@ARTICLE{Vallot2011,
author = {Vallot, Celine and Stransky, Nicolas and Bernard-Pierrot, Isabelle
and Herault, Aurelie and Zucman-Rossi, Jessica and Chapeaublanc,
Elodie and Vordos, Dimitri and Laplanche, Agnes and Benhamou, Simone
and Lebret, Thierry and Southgate, Jennifer and Allory, Yves and
Radvanyi, Francois},
title = {A Novel Epigenetic Phenotype Associated With the Most Aggressive
Pathway of Bladder Tumor Progression},
journal = {J Natl Cancer Inst},
year = {2011},
volume = {103},
pages = {47--60},
number = {1},
month = jan,
abstract = {BackgroundEpigenetic silencing can extend to whole chromosomal regions
in cancer. There have been few genome-wide studies exploring its
involvement in tumorigenesis. MethodsWe searched for chromosomal
regions affected by epigenetic silencing in cancer by using Affymetrix
microarrays and real-time quantitative polymerase chain reaction
to analyze RNA from 57 bladder tumors compared with normal urothelium.
Epigenetic silencing was verified by gene re-expression following
treatment of bladder cell lines with 5-aza-deoxycytidine, a DNA demethylating
agent, and trichostatin A, a histone deacetylase inhibitor. DNA methylation
was studied by bisulfite sequencing and histone methylation and acetylation
by chromatin immunoprecipitation. Clustering was used to distinguish
tumors with multiple regional epigenetic silencing (MRES) from those
without and to analyze the association of this phenotype with histopathologic
and molecular types of bladder cancer. The results were confirmed
with a second panel of 40 tumor samples and extended in vitro with
seven bladder cancer cell lines. All statistical tests were two-sided.
ResultsWe identified seven chromosomal regions of contiguous genes
that were silenced by an epigenetic mechanism. Epigenetic silencing
was not associated with DNA methylation but was associated with histone
H3K9 and H3K27 methylation and histone H3K9 hypoacetylation. All
seven regions were concordantly silenced in a subgroup of 26 tumors,
defining an MRES phenotype. MRES tumors exhibited a carcinoma in
situ-associated gene expression signature (25 of 26 MRES tumors vs
0 of 31 non-MRES tumors, P < 10-14), rarely carried FGFR3 mutations
(one of 26 vs 22 of 31 non-MRES tumors, P < 10-6), and contained
25 of 33 (76%) of the muscle-invasive tumors. Cell lines derived
from aggressive bladder tumors presented epigenetic silencing of
the same regions. ConclusionsWe have identified an MRES phenotype
characterized by the concomitant epigenetic silencing of several
chromosomal regions, which, in bladder cancer, is specifically associated
with the carcinoma in situ gene expression signature.},
comment = {10.1093/jnci/djq470},
url = {http://jnci.oxfordjournals.org/cgi/content/abstract/103/1/47}
}
@ARTICLE{Valles2006,
author = {Vallès, Astrid and Grijpink-Ongering, Lindsay and de Bree, Freddy
M. and Tuinstra, Tinka and Ronken, Eric},
title = {Differential regulation of the CXCR2 chemokine network in rat brain
trauma: Implications for neuroimmune interactions and neuronal survival},
journal = {Neurobiology of Disease},
year = {2006},
volume = {22},
pages = {312--322},
number = {2},
month = may,
abstract = {Chemokine receptors represent promising targets to attenuate inflammatory
responses and subsequent secondary damage after brain injury. We
studied the response of the chemokines CXCL1/CINC-1 and CXCL2/MIP-2
and their receptors CXCR1 and CXCR2 after controlled cortical impact
injury in adult rats. Rapid upregulation of CXCL1/CINC-1 and CXCL2/MIP-2,
followed by CXCR2 (but not CXCR1), was observed after injury. Constitutive
neuronal CXCR2 immunoreactivity was detected in several brain areas,
which rapidly but transiently downregulated upon trauma. A second
CXCR2-positive compartment, mainly colocalized with the activated
microglia/macrophage marker ED1, was detected rapidly after injury
in the ipsilateral cortex, progressively emerging into deeper areas
of the brain later in time. It is proposed that CXCR2 has a dual
role after brain injury: (i) homologous neuronal CXCR2 downregulation
would render neurons more vulnerable to injury, whereas (ii) chemotaxis
and subsequent differentiation of blood-borne cells into a microglial-like
phenotype would be promoted by the same receptor.},
issn = {0969-9961},
keywords = {Brain injury, CXCL1, CINC-1, KC, CXCL2, MIP-2, CXCR2, Leukocytes,
Microglia, Neuroprotection},
url = {http://www.sciencedirect.com/science/article/B6WNK-4J5T5SJ-1/2/2c58d6833268c00a4092fd5f24c69f8a}
}
@ARTICLE{Valta2009,
author = {Valta, Maija P. and Tuomela, Johanna and Vuorikoski, Heikki and Loponen,
Niina and Väänänen, Riina-Minna and Pettersson, Kim and Väänänen,
H. Kalervo and Härkönen, Pirkko L.},
title = {FGF-8b induces growth and rich vascularization in an orthotopic PC-3
model of prostate cancer},
journal = {J. Cell. Biochem.},
year = {2009},
volume = {107},
pages = {769--784},
number = {4},
abstract = {Abstract 10.1002/jcb.22175.abs Fibroblast growth factor 8 (FGF-8)
is expressed at an increased level in a high proportion of prostate
cancers and it is associated with a poor prognosis of the disease.
Our aim was to study the effects of FGF-8b on proliferation of PC-3
prostate cancer cells and growth of PC-3 tumors, and to identify
FGF-8b-associated molecular targets. Expression of ectopic FGF-8b
in PC-3 cells caused a 1.5-fold increase in cell proliferation in
vitro and a four- to fivefold increase in the size of subcutaneous
and orthotopic prostate tumors in nude mice. Tumors expressing FGF-8b
showed a characteristic morphology with a very rich network of capillaries.
This was associated with increased spread of the cancer cells to
the lungs as measured by RT-qPCR of FGF-8b mRNA. Microarray analyses
revealed significantly altered, up- and downregulated, genes in PC-3
cell cultures (169 genes) and in orthotopic PC-3 tumors (61 genes).
IPA network analysis of the upregulated genes showed the strongest
association with development, cell proliferation (CRIP1, SHC1), angiogenesis
(CCL2, DDAH2), bone metastasis (SPP1), cell-to-cell signaling and
energy production, and the downregulated genes associated with differentiation
(DKK-1, VDR) and cell death (CYCS). The changes in gene expression
were confirmed by RT-qPCR. In conclusion, our results demonstrate
that FGF-8b increases the growth and angiogenesis of orthotopic prostate
tumors. The associated gene expression signature suggests potential
mediators for FGF-8b actions on prostate cancer progression and metastasis.
J. Cell. Biochem. 107: 769–784, 2009. © 2009 Wiley-Liss, Inc.},
issn = {1097-4644},
keywords = {angiogenesis, FGF-8, gene expression, microarray, orthotopic prostate
tumors, prostate cancer},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.22175}
}
@ARTICLE{Valvatne2009,
author = {Valvatne, Havard and Syre, Heidi and Kross, Martijn and Stavrum,
Ruth and Ti, Ti and Phyu, Sabai and Grewal, Harleen M. S.},
title = {Isoniazid and rifampicin resistance-associated mutations in Mycobacterium
tuberculosis isolates from Yangon, Myanmar: implications for rapid
molecular testing},
journal = {J. Antimicrob. Chemother.},
year = {2009},
volume = {64},
pages = {694--701},
number = {4},
month = oct,
abstract = {ObjectivesTo evaluate the frequency and nature of mutations in genes
associated with resistance to rifampicin and isoniazid in Mycobacterium
tuberculosis isolates collected from Yangon, Myanmar. MethodsNinety-six
isoniazid-resistant M. tuberculosis isolates, including 29 multidrug-resistant
isolates, were analysed for mutations in the rpoB, katG, inhA, oxyR
and ahpC genes. ResultsMutations in the rpoB gene were detected in
25 (86.2%) of the 29 rifampicin-resistant isolates. Of the 96 isoniazid-resistant
isolates, 61 (63.5%) had mutations in codon 315 of the catalase-peroxidase-encoding
gene (katG). Mutations in codon 315 were observed at a higher frequency
in the multidrug-resistant isolates than in the isoniazid-resistant
isolates (86.2% versus 53.7%, respectively, P = 0.003). Mutations
in the oxyR-ahpC promoter region and in the inhA gene were observed
in 14.6% and 2.1% of the isolates, respectively. Genotyping performed
on the 96 M. tuberculosis isolates revealed a total of 94 different
genotyping patterns. A distinct genotypic pattern was found in 92
isolates, whereas 4 isolates belonged to two clusters with identical
genotypes, suggesting that the majority of the isolates were not
from an outbreak of a single drug-resistant clone. ConclusionsThis
study provides the first molecular characterization of isoniazid-
and rifampicin-resistant M. tuberculosis isolates from Myanmar and
gives information on the molecular basis for rifampicin and isoniazid
drug resistance in M. tuberculosis. The study generates useful information
for the development of potential rapid molecular drug susceptibility
tests.},
url = {http://jac.oxfordjournals.org/cgi/content/abstract/64/4/694}
}
@ARTICLE{Valverde2008,
author = {Valverde, Claudio and Livny, Jonathan and Schlüter, Jan-Philip and
Reinkensmeier, Jan and Becker, Anke and Parisi, Gustavo},
title = {Prediction of Sinorhizobium meliloti sRNA genes and experimental
detection in strain 2011},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {416},
number = {1},
abstract = {BACKGROUND:Small non-coding RNAs (sRNAs) have emerged as ubiquitous
regulatory elements in bacteria and other life domains. However,
few sRNAs have been identified outside several well-studied species
of gamma-proteobacteria and thus relatively little is known about
the role of RNA-mediated regulation in most other bacterial genera.
Here we have conducted a computational prediction of putative sRNA
genes in intergenic regions (IgRs) of the symbiotic a-proteobacterium
S. meliloti 1021 and experimentally confirmed the expression of dozens
of these candidate loci in the closely related strain S. meliloti
2011.RESULTS:Our first sRNA candidate compilation was based mainly
on the output of the sRNAPredictHT algorithm. A thorough manual sequence
analysis of the curated list rendered an initial set of 18 IgRs of
interest, from which 14 candidates were detected in strain 2011 by
Northern blot and/or microarray analysis. Interestingly, the intracellular
transcript levels varied in response to various stress conditions.
We developed an alternative computational method to more sensitively
predict sRNA-encoding genes and score these predicted genes based
on several features to allow identification of the strongest candidates.
With this novel strategy, we predicted 60 chromosomal independent
transcriptional units that, according to our annotation, represent
strong candidates for sRNA-encoding genes, including most of the
sRNAs experimentally verified in this work and in two other contemporary
studies. Additionally, we predicted numerous candidate sRNA genes
encoded in megaplasmids pSymA and pSymB. A significant proportion
of the chromosomal- and megaplasmid-borne putative sRNA genes were
validated by microarray analysis in strain 2011.CONCLUSION:Our data
extend the number of experimentally detected S. meliloti sRNAs and
significantly expand the list of putative sRNA-encoding IgRs in this
and closely related a-proteobacteria. In addition, we have developed
a computational method that proved useful to predict sRNA-encoding
genes in S. meliloti. We anticipate that this predictive approach
can be flexibly implemented in many other bacterial species.},
doi = {10.1186/1471-2164-9-416},
issn = {1471-2164},
pubmedid = {18793445},
url = {http://www.biomedcentral.com/1471-2164/9/416}
}
@ARTICLE{Vambergue2007,
author = {Vambergue, A. and Fajardy, I. and Dufour, P. and Valat, A.S. and
Vandersippe, M. and Fontaine, P. and Danze, P.M. and Rousseaux, J.},
title = {No loss of genomic imprinting of IGF-II and H19 in placentas of diabetic
pregnancies with fetal macrosomia},
journal = {Growth Hormone \& IGF Research},
year = {2007},
volume = {17},
pages = {130--136},
number = {2},
month = apr,
abstract = {Objectives Fetal macrosomia is a common complication of maternal diabetes
mellitus and is associated with substantial morbidity, but the precise
cellular and molecular mechanisms that induce fetal macrosomia are
not well understood. The imprinted genes IGF-II and H19 are crucial
for placental development and fetal growth. The term placentas from
diabetic pregnancies express more insulin-like growth factor II (IGF-II)
than those from normal pregnancies. Deregulation of their imprinting
status is observed in the macrosomia-associated syndrome, the Beckwith-Wiedemann
syndrome. The aim of this study was to determine whether loss of
imprinting hence biallelic expression was also a hallmark of macrosomia
in diabetic pregnancies.Design and methods IGF-II and H19 maternal
and paternal expressions were studied in placentas from two groups
of type 1 diabetic mothers: one with macrosomic babies and the other
with babies of normal weight. Maternal or paternal allele specific
expressions were defined by using DNA polymorphic markers of the
IGF-II and H19 genes. RFLP analysis was performed on PCR products
from genomic DNA of the father, the mother and the child, and on
RT-PCR products from placental mRNA.Results RFLP analysis showed
that the IGF-II gene remains paternally expressed and the H19 gene
remains maternally expressed in all placentas examined, independently
of the birth weight status.Conclusions These results suggest that,
in contrast with Beckwith-Wiedemann syndrome-associated macrosomia,
loss of imprinting for IGF-II or H19 is not a common feature of diabetic
pregnancies associated with macrosomia.},
issn = {1096-6374},
keywords = {Genomic imprinting, Human placental tissue, Macrosomia, Diabetes mellitus,
IGF-II gene, H19 gene},
url = {http://www.sciencedirect.com/science/article/B6WG5-4N2DVY1-1/2/8760d92bf3bd25f69128cda297a91950}
}
@ARTICLE{Vambergue2004,
author = {Vambergue, A. and Fajardy, I. and Julio, Chr. and Devisme, L. and
Valat, A.-S. and Vandersippe, M. and Danze, P.-M. and Fontaine, P.
and Rousseaux, J.},
title = {P173 - Mise au point d'un outil d'analyse de l'expression génétique
placentaire pour des grossesses avec anomalies de la tolérance glucidique},
journal = {Annales d'Endocrinologie},
year = {2004},
volume = {65},
pages = {374--375},
number = {4},
month = sep,
issn = {0003-4266},
url = {http://www.sciencedirect.com/science/article/B8CXC-4R7N18R-79/2/aa3cc0d5ef53c61f3511a18fac6e3190}
}
@ARTICLE{Vambergue2004a,
author = {Vambergue, A. and Fajardy, I. and Valat, A.-S. and Vandersippe, M.
and Danze, P.-M. and Rousseaux, J. and Fontaine, P.},
title = {P172 - Absence de levée d'empreinte parentale des gènes IGf2 et H19
dans les placentas de grossesses diabétiques avec macrosomie},
journal = {Annales d'Endocrinologie},
year = {2004},
volume = {65},
pages = {374--374},
number = {4},
month = sep,
issn = {0003-4266},
url = {http://www.sciencedirect.com/science/article/B8CXC-4R7N18R-78/2/f3d9027dd650af1ab41c0d1809468aca}
}
@ARTICLE{VanBoeijen2010,
author = {Van Boeijen, Ineke K. H. and Chavaroche, Anais A. E. and Valderrama,
Wladir B. and Moezelaar, Roy and Zwietering, Marcel H. and Abee,
Tjakko},
title = {Population Diversity of Listeria monocytogenes LO28: Phenotypic and
Genotypic Characterization of Variants Resistant to High Hydrostatic
Pressure},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {2225--2233},
number = {7},
month = apr,
abstract = {A comparative phenotype analysis of 24 Listeria monocytogenes LO28
stress-resistant variants obtained after high-pressure treatment
was performed to assess their robustness and growth performance under
a range of food-relevant conditions. In addition, genetic analysis
was conducted to characterize the promoter regions and open reading
frames of the class I and III transcriptional repressors CtsR and
HrcA, which control production of specific sets of stress proteins.
Analysis of stress survival capacity, motility, biofilm formation,
and growth under various conditions showed all variants to be more
resistant to pressure and heat than the wild type; however, differences
among variants were observed in acid resistance, growth rate, motility,
and biofilm-forming capacity. Genetic analysis revealed no variation
in the genetic make-up of hrcA and its upstream region, but two variants
had deletions in the upstream region of ctsR and seven variants had
mutations in the ctsR gene itself. The results of the characterization
were cluster analyzed to obtain insight into the diversity of variants.
Ten unique variants and three clusters with specific features could
be identified: one cluster consisting of seven variants having a
mutation in the CtsR regulator gene, one cluster containing two variants
with an aerobic biofilm formation capacity similar to that of the
wild type, and a cluster composed of five immotile variants. The
large population diversity of L. monocytogenes stress-resistant variants
signifies the organism's genetic flexibility, which in turn may contribute
to the survival and persistence of this human pathogen in food-processing
environments.},
url = {http://aem.asm.org/cgi/content/abstract/76/7/2225}
}
@ARTICLE{VanBruaene2009,
author = {Van Bruaene, Nicholas and Derycke, Lara and Perez-Novo, Claudina
Angela and Gevaert, Philippe and Holtappels, Gabriele and De Ruyck,
Natalie and Cuvelier, Claude and Van Cauwenberge, Paul and Bachert,
Claus},
title = {TGF-[beta] signaling and collagen deposition in chronic rhinosinusitis},
journal = {Journal of Allergy and Clinical Immunology},
year = {2009},
volume = {124},
pages = {253--259.e2},
number = {2},
month = aug,
abstract = {Background Chronic rhinosinusitis is an inflammatory disease with
distinct cytokine and remodeling patterns.Objective The objective
was to analyze the presence of TGF-[beta] isoforms, receptors, intracellular
signaling, and collagen deposition in chronic rhinosinusitis.Methods
Sinonasal mucosal samples obtained from chronic rhinosinusitis with
nasal polyps (CRSwNP; n = 13), chronic rhinosinusitis without nasal
polyps (CRSsNP; n = 13), and controls (n = 10) were analyzed for
TGF-[beta] isoforms 1 and 2 by means of ELISA and IHC, and for TGF-[beta]
R1, 2, and 3 by RT-PCR and IHC. As downstream proteins, phospho-Smad
2 (pSmad 2) and collagen were analyzed by performing immunostaining
and picrosirius red staining, respectively.Results TGF-[beta] 1 and
2 protein concentrations, TGF-[beta] receptor (R) I and TGF-[beta]
RIII mRNA expression, the number of pSmad 2-positive cells, and total
collagen amount were significantly higher in CRSsNP versus controls.
In CRSwNP, TGF-[beta] 1 protein concentration, TGF-[beta] RII and
TGF-[beta] RIII mRNA expression, the number of pSmad 2-positive cells,
and total collagen amount were significantly lower versus controls.
Only TGF-[beta] 2 protein was found higher in CRSwNP versus controls.Conclusion
A high TGF-[beta] 1 protein expression, increased TGF-[beta] RI expression,
and a high number of pSmad 2-positive cells all indicate an enhanced
TGF-[beta] signaling in CRSsNP, whereas a low TGF-[beta] 1 protein
concentration, a decreased expression of TGF-[beta] RII, and a low
number of pSmad 2-positive cells in CRSwNP indicate a low level of
TGF-[beta] signaling in CRSwNP. These findings are compatible with
the remodeling patterns observed, reflected by a lack of collagen
in CRSwNP, and excessive collagen production with thickening of the
collagen fibers in the extracellular matrix in CRSsNP.},
issn = {0091-6749},
keywords = {Chronic rhinosinusitis, collagen, inflammation, nasal polyposis, phospho-Smad
2, remodeling, TGF-[beta]},
url = {http://www.sciencedirect.com/science/article/B6WH4-4WFGRKP-3/2/2cd7caa859619bddd6b70665e8a690ee}
}
@ARTICLE{VanBruaene2008,
author = {Van Bruaene, Nicholas and Pérez-Novo, Claudina Angela and Basinski,
Tomasz M. and Van Zele, Thibaut and Holtappels, Gabriele and De Ruyck,
Natalie and Schmidt-Weber, Carsten and Akdis, Cezmi and Van Cauwenberge,
Paul and Bachert, Claus and Gevaert, Philippe},
title = {T-cell regulation in chronic paranasal sinus disease},
journal = {Journal of Allergy and Clinical Immunology},
year = {2008},
volume = {121},
pages = {1435--1441.e3},
number = {6},
month = jun,
abstract = {Background Chronic rhinosinusitis is an inflammatory disease with
distinct cytokine and remodeling patterns. Chronic rhinosinusitis
with nasal polyps (CRSwNP) is characterized by a TH2-skewed eosinophilic
inflammation, whereas chronic rhinosinusitis without nasal polyps
(CRSsNP) represents a predominant TH1 milieu.Objective We aimed to
study the direct tissue expression of transcription factors for T-cell
subpopulations, including T regulatory cells, in relation to the
cytokine expression patterns in the different disease subgroups.Methods
The expression of forkhead box P3 (FOXP3), T-box transcription factor
(T-bet), GATA-3, retinoid acid-related orphan receptor C (RORc),
the suppressive cytokines TGF-[beta]1 and IL-10, and TH1/ TH2/ TH17
cytokines (IFN-[gamma], IL-4, IL-5, IL-13, IL-17) were analyzed by
means of RT-PCR in 13 CRSsNP, 16 CRSwNP, and 10 control samples.
Additional protein measurements were performed for TGF-[beta]1 and
IFN-[gamma].Results In CRSwNP, we observed a significantly lower
FOXP3 mRNA and TGF-[beta]1 protein expression, but a significantly
higher T-bet, GATA-3, IL-5, and IL-13 mRNA expression compared with
controls, whereas RORc was not significantly different compared with
controls. In CRSsNP, FOXP3, T-bet, GATA-3, and RORc expression was
not significantly different from controls, whereas TGF-[beta]1 mRNA,
IFN-[gamma] mRNA, and protein were significantly higher in CRSsNP
compared with controls. For IL-17, no significant differences were
noted among all groups.Conclusion We demonstrate for the first time
a decreased FOXP3 expression accompanied by an upregulation of T-bet
and GATA-3 and a downregulation of TGF-[beta]1 in CRSwNP versus controls
and CRSsNP.},
issn = {0091-6749},
keywords = {Chronic rhinosinusitis, FOXP3, nasal polyps, T-cell polarization,
TGF-[beta]1, transcription factors, T regulatory cell},
url = {http://www.sciencedirect.com/science/article/B6WH4-4S9FH0W-1/2/26d782e10bbe63ad84fe9815a4e77c29}
}
@ARTICLE{VanCampenhout2009,
author = {Van Campenhout, Ann and Moran, Corey S. and Parr, Adam and Clancy,
Paula and Rush, Catherine and Jakubowski, Hieronim and Golledge,
Jonathan},
title = {Role of homocysteine in aortic calcification and osteogenic cell
differentiation},
journal = {Atherosclerosis},
year = {2009},
volume = {202},
pages = {557--566},
number = {2},
month = feb,
abstract = {Background The role of homocysteine in atherosclerosis is unclear.
We examined the relationship between plasma homocysteine and infrarenal
aortic calcification, the presence of homocysteine in human atheroma
and the influence of homocysteine on osteogenic differentiation in
vitro.Methods and results In 194 patients with symptomatic peripheral
artery disease or abdominal aortic aneurysm, fasting plasma total
homocysteine was independently associated with the severity of infrarenal
aortic calcification measured by Computer Tomography Angiography
(odds ratio 1.91, 95% confidence interval 1.17-3.21 for calcification
>=median). Homocysteine was identified in all 60 atheroma biopsies
from 16 patients undergoing endarterectomy, and concentrations were
significantly greater in the calcified biopsies (p = 0.003). In vitro
studies demonstrated that 100 [mu]mol/L homocysteine doubled the
calcium deposition by mesenchymal stem cells during 16 days incubation
in osteogenic medium (74 ± 4 compared to 42 ± 5 [mu]g calcium/well
without homocysteine, p < 0.001). Homocysteine also stimulated monocytic
THP1 cells to promote aortic smooth muscle cell calcification as
evidenced by significant higher calcium deposition and alkaline phosphatase
activity compared to incubation without homocysteine (p <= 0.05).Conclusions
Homocysteine plays an important role in vascular calcification via
multiple mechanisms. The presence of homocysteine in atheroma and
its ability to enhance osteogenic cell differentiation may partly
explain the association of homocysteine with atherosclerotic events.},
issn = {0021-9150},
keywords = {Calcification, Homocysteine, Atheroma, Osteogenic differentiation},
url = {http://www.sciencedirect.com/science/article/B6T12-4SM62KJ-6/2/629d1de2631a25bf39dd84876d41d1f1}
}
@ARTICLE{VanDaele2010,
author = {Van Daele, Douglas J.},
title = {Quantitative PCR analysis of laryngeal muscle fiber types},
journal = {Journal of Communication Disorders},
year = {2010},
volume = {43},
pages = {327--334},
number = {4},
month = jul,
abstract = {Voice and swallowing dysfunction as a result of recurrent laryngeal
nerve paralysis can be improved with vocal fold injections or laryngeal
framework surgery. However, denervation atrophy can cause late-term
clinical failure. A major determinant of skeletal muscle physiology
is myosin heavy chain (MyHC) expression, and previous protein analyses
have shown changes in laryngeal muscle fiber MyHC isoform with denervation.
RNA analyses in this setting have not been performed, and understanding
RNA levels will allow interventions better designed to reverse processes
such as denervation in the future. Total RNA was extracted from bilateral
rat thyroarytenoid (TA), posterior cricoarytenoid (PCA), and cricothyroid
(CT) muscles in rats. Primers were designed using published MyHC
isoform sequences. SYBR Green real-time reverse transcription-polymerase
chain reaction (SYBR-RT-PCR) was used for quantification. The electropherogram
showed a clear separation of total RNA to 28S and 18S subunits. Melting
curves illustrated single peaks for all type MyHC primers. All MyHC
isoforms were identified in all muscles with various degrees of expression.
Quantitative PCR is a sensitive method to detect MyHC isoforms in
laryngeal muscle. Isoform expression using mRNA analysis was similar
to previous analyses but showed some important differences. This
technique can be used to quantitatively assess response to interventions
targeted to maintain muscle bulk after denervation. Learning outcomes:
(1) Readers will be able to describe the relationship between myosin
heavy chain expression and muscle contractile properties. (2) Readers
will be able to separate myosin heavy chain isoforms into slow and
fast twitch phenotypes. (3) Readers will be able to describe differential
muscle isoform expression between different laryngeal muscles. (4)
Readers will be able to compare this study to other modalities of
determining muscle fiber type.},
booktitle = {ASHA-NIH-NIDCD 2009 Research Symposium: Neural regeneration and communication
processes},
issn = {0021-9924},
url = {http://www.sciencedirect.com/science/article/B6T85-4YT6D5V-6/2/aae2103944b0717cec3ae2bdfb1e4fbb}
}
@ARTICLE{VanDeParre2005,
author = {Van De Parre, Tim J.L. and Martinet, Wim and Schrijvers, Dorien M.
and Herman, Arnold G. and De Meyer, Guido R.Y.},
title = {mRNA but not plasmid DNA is efficiently transfected in murine J774A.1
macrophages},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {327},
pages = {356--360},
number = {1},
month = feb,
abstract = {Previous studies demonstrated that macrophages are difficult to transfect.
In the present study, we investigated whether J774A.1 macrophages
can be efficiently transfected using nucleofector technology. Nucleofection
of J774A.1 macrophages with mRNA resulted in transfection efficiencies
up to 75% without cell death as compared to control pulsed macrophages.
In contrast, introduction of DNA into J774A.1 cells caused apoptosis
without expression of the gene of interest. Our results show that
mRNA nucleofection is a new high-speed transfection method for macrophages.},
issn = {0006-291X},
keywords = {Gene transfer, Green fluorescent protein, J774A.1 macrophage, Nucleofection,
Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6WBK-4F1GN4P-8/2/0b325f477cba4ad59a2ec1f7095c56f6}
}
@ARTICLE{VanDeWalle2010,
author = {Van De Walle, Jacqueline and During, Alexandrine and Piront, Neil
and Toussaint, Olivier and Schneider, Yves-Jacques and Larondelle,
Yvan},
title = {Physio-pathological parameters affect the activation of inflammatory
pathways by deoxynivalenol in Caco-2 cells},
journal = {Toxicology in Vitro},
year = {2010},
volume = {24},
pages = {1890--1898},
number = {7},
month = oct,
abstract = {The intake of deoxynivalenol (DON), a mycotoxin contaminating cereal
food items, causes gastro-intestinal illness in human and animal.
This study investigated whether intracellular inflammatory cascades
(MAPKs and NF-[kappa]B), cell maturity (proliferating vs. differentiated),
cell state (control vs. inflamed) and exposure duration (chronic
vs. acute) affect IL-8 secretion and PGE-2 synthesis in Caco-2 cells
exposed to plausible intestinal concentrations (50, 500 and 5000 ng/ml)
of DON. IL-8 secretion and PGE-2 synthesizing capacity were dose-dependently
upregulated in differentiated Caco-2 cells exposed to DON during
24 h, reaching an increase of ~25 and 1.7-fold respectively, whereas
transcript level of IL-8 and COX-2 were increased by ~40 and 17-fold.
Similar results were obtained with proliferating cells. The upregulation
decreased upon simultaneous incubation with inhibitors of MAPKs ERK1/2
or p38 or of transcription factor NF-[kappa]B. IL-8 secretion and
PGE-2 synthesizing capacity increased respectively by ~15 and 2-fold
after chronic 21 day incubation with DON (50 ng/ml). IL-8 production
was exacerbated (~510-fold versus negative control) upon simultaneous
exposure to inflammatory stimuli. These results suggest activation
of inflammatory pathways in intestinal epithelial cells exposed chronically
or acutely to DON. The sensitivity to DON, whereas not affected by
cell differentiation, is exacerbated by the presence of additional
stimuli.},
issn = {0887-2333},
keywords = {Caco-2, Deoxynivalenol, Inflammatory cascades, Cell differentiation,
Intestinal inflammation},
url = {http://www.sciencedirect.com/science/article/B6TCP-50HP2SN-2/2/ef4f024c9d2e2be64af3afde112b4280}
}
@ARTICLE{VanDenBroeck2008,
author = {Van Den Broeck, Arnaud and Brambilla, Elisabeth and Moro-Sibilot,
Denis and Lantuejoul, Sylvie and Brambilla, Christian and Eymin,
Beatrice and Khochbin, Saadi and Gazzeri, Sylvie},
title = {Loss of Histone H4K20 Trimethylation Occurs in Preneoplasia and Influences
Prognosis of Non-Small Cell Lung Cancer},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {7237--7245},
number = {22},
month = nov,
abstract = {Purpose: Epigenetic modifications of histone have crucial roles in
the control of gene activity, nuclear architecture, and genomic stability.
In this respect, they may contribute to the development and progression
of cancer. We investigated whether epigenetic changes of histone
H4 are involved in lung carcinogenesis. Experimental Design: Epigenetic
modifications of histone H4 were studied by immunohistochemistry
in normal lung and 157 lung carcinoma using antibodies specifically
recognizing the acetylated (Ac) lysines 5 (K5), K8, K12, K16, and
trimethylated (me3) K20 residues of histone H4. Western blotting
was used to validate the immunohistochemistry results. H4K20me3 was
also studied in 17 preneoplastic lesions. Expression of the Suv4-20h1/2
trimethyltransferases was analyzed by quantitative reverse transcription-PCR
in a subset of tumor samples. Results: As compared with normal lung,
cancer cells displayed an aberrant pattern of histone H4 modifications
with hyperacetylation of H4K5/H4K8, hypoacetylation of H4K12/H4K16,
and loss of H4K20 trimethylation. Alteration of H4K20 trimethylation
was frequent in squamous cell carcinoma (67%) and was observed in
early precursors lesions in which the level of H4K20me3 staining
strongly decreased with disease progression. In adenocarcinoma, the
down-regulation of H4K20me3 was less frequent (28%) but allowed the
identification of a subgroup of stage I adenocarcinoma patients with
reduced survival (P = 0.007). Loss of H4K20 trimethylation was associated
with decreased expression of Suv4-20h2, a specific H4K20 trimethyltransferase
involved in telomere length maintenance. Conclusions: Our findings
indicate an important role of histone H4 modifications in bronchial
carcinogenesis and highlight H4K20me3 as a candidate biomarker for
early detection of and therapeutic approaches to lung cancer.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/22/7237}
}
@ARTICLE{VandenOever2006,
author = {Van den Oever, Michel C. and Spijker, Sabine and Li, Ka Wan and Jiménez,
Connie R. and Koya, Eisuke and Van der Schors, Roel C. and Gouwenberg,
Yvonne and Binnekade, Rob and De Vries, Taco J. and Schoffelmeer,
Anton N. M. and Smit, August B.},
title = {A Proteomics Approach to Identify Long-Term Molecular Changes in
Rat Medial Prefrontal Cortex Resulting from Sucrose Self-Administration},
journal = {Journal of Proteome Research},
year = {2006},
volume = {5},
pages = {147-154},
number = {1},
doi = {10.1021/pr050303y},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr050303y},
url = {http://pubs.acs.org/doi/abs/10.1021/pr050303y}
}
@ARTICLE{VanDenWijngaard2009,
author = {Van Den Wijngaard, R. M. and Klooker, T. K. and Welting, O. and Stanisor,
O. I. and Wouters, M. M. and Van Der Coelen, D. and Bulmer, D. C.
and Peeters, P. J. and Aerssens, J. and De Hoogt, R. and Lee, K.
and De Jonge, W. J. and Boeckxstaens, G. E.},
title = {Essential role for TRPV1 in stress-induced (mast cell-dependent)
colonic hypersensitivity in maternally separated rats},
journal = {Neurogastroenterology \& Motility},
year = {2009},
volume = {21},
pages = {1107--e94},
number = {10},
abstract = {Abstract  Irritable bowel syndrome is in part characterized by an
increased sensitivity to colonic distension. Stress is an important
trigger factor for symptom generation. We hypothesized that stress
induces visceral hypersensitivity via mast cell degranulation and
transient receptor ion channel 1 (TRPV1) modulation. We used the
rat model of neonatal maternal separation (MS) to investigate this
hypothesis. The visceromotor response to colonic distention was assessed
in adult MS and non-handled (NH) rats before and after acute water
avoidance (WA) stress. We evaluated the effect of the mast cell stabilizer
doxantrazole, neutralizing antiserum against the mast cell mediator
nerve growth factor (NGF) and two different TRPV1 antagonists; capsazepine
(non-specific) and SB-705498 (TRPV1-specific). Immunohistochemistry
was used to assess post-WA TRPV1 expression in dorsal root ganglia
and the presence of immunocytes in proximal and distal colon. Retrograde
labelled and microdissected dorsal root ganglia sensory neurons were
used to evaluate TRPV1 gene transcription. Results showed that acute
stress induces colonic hypersensitivity in MS but not in NH rats.
Hypersensitivity was prevented by prestress administration of doxantrazole
and anti-NGF. Capsazepine inhibited and SB-705498 reversed poststress
hypersensitivity. In MS rats, acute stress induced a slight increase
in colonic mast cell numbers without further signs of inflammation.
Post-WA TRPV1 transcription and expression was not higher in MS than
NH rats. In conclusion, the present data on stress-induced visceral
hypersensitivity confirm earlier reports on the essential role of
mast cells and NGF. Moreover, the results also suggest that TRPV1
modulation (in the absence of overt inflammation) is involved in
this response. Thus, mast cells and TRPV1 are potential targets to
treat stress-induced visceral hypersensitivity.},
issn = {1365-2982},
keywords = {mast cells, maternal separation, stress, transient receptor ion channel
1, visceral hypersensitivity},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2982.2009.01339.x}
}
@ARTICLE{VanderAuwera2004,
author = {Van der Auwera, Ilse and Van Laere, Steven J. and Van den Eynden,
Gert G. and Benoy, Ina and van Dam, Peter and Colpaert, Cecile G.
and Fox, Stephen B. and Turley, Helen and Harris, Adrian L. and Van
Marck, Eric A. and Vermeulen, Peter B. and Dirix, Luc Y.},
title = {Increased Angiogenesis and Lymphangiogenesis in Inflammatory versus
Noninflammatory Breast Cancer by Real-Time Reverse Transcriptase-PCR
Gene Expression Quantification},
journal = {Clin. Cancer Res.},
year = {2004},
volume = {10},
pages = {7965--7971},
number = {23},
month = dec,
abstract = {Purpose: Inflammatory breast cancer is a distinct and aggressive form
of locally advanced breast cancer with unique clinical and pathological
features. Recently, histologic evidence of intense angiogenesis was
found in inflammatory breast cancer specimens. The aim of this study
was to confirm the angiogenic phenotype of inflammatory breast cancer
and to investigate its potential to induce lymphangiogenesis. Experimental
Design: Real-time quantitative reverse transcriptase-PCR was used
to measure levels of mRNA of tumor angiogenesis and lymphangiogenesis-related
factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D,
Flt-1, KDR, Flt-4, Ang-1, Ang-2, Tie-1, Tie-2, cyclooxygenase-2,
fibroblast growth factor-2 (FGF-2), Egr-1, Prox-1, and LYVE-1] in
tumor specimens of 16 inflammatory breast cancer and 20 noninflammatory
breast cancer patients. Tissue microarray technology and immunohistochemistry
were used to study differential protein expression of some of the
angiogenic factors in inflammatory breast cancer and noninflammatory
breast cancer. Active lymphangiogenesis was further assessed by measuring
lymphatic endothelial cell proliferation. Results: Inflammatory breast
cancer specimens had significantly higher mRNA expression levels
than noninflammatory breast cancer specimens of the following genes:
KDR (P = 0.033), Ang-1, (P = 0.0001), Tie-1 (P = 0.001), Tie-2 (P
= 0.001), FGF-2 (P = 0.002), VEGF-C (P = 0.001), VEGF-D (P = 0.012),
Flt-4 (P = 0.001), Prox-1 (P = 0.005), and LYVE-1 (P = 0.013). High
mRNA levels of FGF-2 and cyclooxygenase-2 corresponded to increased
protein expression by immunohistochemistry. Inflammatory breast cancer
specimens contained significantly higher fractions of proliferating
lymphatic endothelial cells than noninflammatory breast cancer specimens
(P = 0.033). Conclusions: Using real-time quantitative reverse transcriptase-PCR
and immunohistochemistry, we confirmed the intense angiogenic activity
in inflammatory breast cancer and demonstrated the presence of active
lymphangiogenesis in inflammatory breast cancer. This may help explain
the high metastatic potential of inflammatory breast cancer by lymphatic
and hematogenous route. Both pathways are potential targets for the
treatment of inflammatory breast cancer.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/10/23/7965}
}
@ARTICLE{VanderFlier2007,
author = {Van der Flier, Laurens G. and Sabates-Bellver, Jacob and Oving, Irma
and Haegebarth, Andrea and De Palo, Mariagrazia and Anti, Marcello
and Van Gijn, Marielle E. and Suijkerbuijk, Saskia and Van de Wetering,
Marc and Marra, Giancarlo and Clevers, Hans},
title = {The Intestinal Wnt/TCF Signature},
journal = {Gastroenterology},
year = {2007},
volume = {132},
pages = {628--632},
number = {2},
month = feb,
abstract = {Background & Aims: In colorectal cancer, activating mutations in the
Wnt pathway transform epithelial cells through the inappropriate
expression of a TCF4 target gene program, which is physiologically
expressed in intestinal crypts. Methods: We have now performed an
exhaustive array-based analysis of this target gene program in colorectal
cancer cell lines carrying an inducible block of the Wnt cascade.
Independently, differential gene-expression profiles of human adenomas
and adenocarcinomas vs normal colonic epithelium were obtained. Results
Expression analyses of approximately 80 genes common between these
data sets were performed in a murine adenoma model. The combined
data sets describe a core target gene program, the intestinal Wnt/TCF
signature gene set, which is responsible for the transformation of
human intestinal epithelial cells. Conclusions The genes were invariably
expressed in adenomas, yet could be subdivided into 3 modules, based
on expression in distinct crypt compartments. A module of 17 genes
was specifically expressed at the position of the crypt stem cell.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4KNV2KX-6/2/b013ddeed9de4aac91f912688c7bb390}
}
@ARTICLE{VanDerHel2009,
author = {Van Der Hel, W. Saskia and Verlinde, Suzanne A.M.W. and Meijer, Dimphna
H.M. and De Wit, Marina and Rensen, Marije G. and Van Gassen, Koen
L.I. and Van Rijen, Peter C. and Van Veelen, Cees W.M. and De Graan,
Pierre N.E.},
title = {Hippocampal distribution of vesicular glutamate transporter 1 in
patients with temporal lobe epilepsy},
journal = {Epilepsia},
year = {2009},
volume = {50},
pages = {1717--1728},
number = {7},
abstract = {Summary Purpose:  Vesicular glutamate transporters (VGLUTs) are
responsible for loading synaptic vesicles with glutamate, determining
the phenotype of glutamatergic neurons, and have been implicated
in the regulation of quantal size and presynaptic plasticity. We
analyzed VGLUT subtype expression in normal human hippocampus and
tested the hypothesis that alterations in VGLUT expression may contribute
to long-term changes in glutamatergic transmission reported in patients
with temporal lobe epilepsy (TLE). Methods:  VGLUT immunohistochemistry,
immunofluorescence, in situ hybridization, Western blotting, and
quantitative polymerase chain reaction (qPCR) were performed on biopsies
from TLE patients without (non-HS) and with hippocampal sclerosis
(HS) and compared to autopsy controls and rat hippocampus. VGLUT1
expression was compared with synaptophysin, neuropeptide Y (NPY),
and Timm’s staining. Results:  VGLUT1 was the predominant VGLUT
in human hippocampus and appeared to be localized to presynaptic
glutamatergic terminals. In non-HS hippocampi, VGLUT1 protein levels
were increased compared to control and HS hippocampi in all subfields.
In HS hippocampi VGLUT1 expression was decreased in subfields with
severe neuronal loss, but strongly up-regulated in the dentate gyrus,
characterized by mossy fiber sprouting. Discussion:  VGLUT1 is
used as marker for glutamatergic synapses in the human hippocampus.
In HS hippocampi VGLUT1 up-regulation in the dentate gyrus probably
marks new glutamatergic synapses formed by mossy fiber sprouting.
Our data indicate that non-HS patients have an increased capacity
to store glutamate in vesicles, most likely due to an increase in
translational processes or upregulation of VGLUT1 in synapses from
afferent neurons outside the hippocampus. This up-regulation may
increase glutamatergic transmission, and thus contribute to increased
extracellular glutamate levels and hyperexcitability.},
issn = {1528-1167},
keywords = {Vesicular glutamate transporters, Temporal lobe epilepsy, Human, VGLUT1,
Mossy fiber sprouting},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1528-1167.2009.02054.x}
}
@ARTICLE{VanDolah2007,
author = {Van Dolah, Frances M. and Lidie, Kristy B. and Morey, Jeanine S.
and Brunelle, Stephanie A. and Ryan, James C. and Monroe, Emily A.
and Haynes, Bennie L.},
title = {Microarray analysis of diurnal- and circadian-regulated genes in
the florida red-tide dinoflagellate karenia brevis (dinophyceae)1},
journal = {Journal of Phycology},
year = {2007},
volume = {43},
pages = {741--752},
number = {4},
abstract = {The photoperiod plays a central role in regulating the physiology
and behavior of photosynthetic phytoplankton, and many of these processes
are controlled by an underlying circadian rhythm. In dinoflagellates,
circadian rhythms have been shown to depend largely on posttranscriptional
regulation. However, the extent to which dinoflagellates modulate
transcript levels to regulate gene expression in response to light
and dark has not been addressed. Here we utilized an oligonucleotide
microarray containing probes to 4629 unique genes from the Florida
red-tide dinoflagellate Karenia brevis (C. C. Davis) G. Hansen et
Moestrup to characterize global gene expression patterns over a 24Â h
day in cells exposed to a 16:8 light:dark cycle (LD treatment) and
cells under constant light (LL treatment). We determined that 9.8%
of the queried genes were differentially expressed during LD, while
3% of genes were differentially expressed over the 24Â h day when
exposed to LL. Most genes exhibited either peak or minimum expression
in early dark phase. Of the 453 differentially expressed genes in
LD, 104 were assigned predicted annotations based on BLASTX searches.
Few of the identifiable genes that were differentially expressed
in LD appear to be under circadian control, as their cyclical expression
did not persist in LL. Analysis of coordinately expressed genes revealed
several novel insights into dinoflagellate gene expression, including
an unusually high representation of genes involved in post-transcriptional
processing of RNA and protein turnover, the regulation of PSII genes
in response to light and dark, and the absence of transcriptional
regulation of cell-cycle genes.},
issn = {1529-8817},
keywords = {cell cycle, circadian, dinoflagellate, diurnal, gene expression, microarray},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1529-8817.2007.00354.x}
}
@ARTICLE{VanDuy2007,
author = {Van Duy, Nguyen and Mäder, Ulrike and Tran, Ngoc Phuong and Cavin,
Jean-François and Tam, Le Thi and Albrecht, Dirk and Hecker, Michael
and Antelmann, Haike},
title = {The proteome and transcriptome analysis of Bacillus subtilis in response
to salicylic acid},
journal = {Proteomics},
year = {2007},
volume = {7},
pages = {698--710},
number = {5},
abstract = {Abstract 10.1002/pmic.200600706.abs Phenolic acids that are present
in plant–soil ecosystems can be considered as toxins which induce
specific stress responses in microorganisms. In this paper, we have
analyzed the global response of the soil bacterium Bacillus subtilis
to salicylic acid using proteomics and transcriptomics. The results
demonstrate that salicylic acid caused predominantly the induction
of the SigmaB-dependent general stress response in B. subtilis which
is not related to the acidic conditions. Treatment of B. subtilis
with growth-inhibitory concentrations of 4 mM salicylic acid caused
protein damage in B. subtilis as reflected by the induction of the
CtsR and Spx regulons. Both phenolic acid decarboxylases (pads) of
B. subtilis padC and bsdBCD (yclBCD) were induced by 4 mM salicylic
acid that were previously shown to be involved in decarboxylation
and detoxification of different phenolic acids. Deletion of the putative
LysR-type regulator encoded by the divergently transcribed bsdA (yclA)
gene upstream of the bsdBCD operon revealed that BsdA is the transcriptional
activator of bsdBCD expression in response to salicylic acid. Phenotype
analysis of bsdA and padC single and double mutants demonstrated
that both pads confer resistance to salicylic acid in B. subtilis.},
issn = {1615-9861},
keywords = {Bacillus subtilis, Phenolic acid decarboxylases, Salicylic acid, Transcriptome},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200600706}
}
@ARTICLE{VanDuy2007a,
author = {Van Duy, Nguyen and Wolf, Carmen and Mäder, Ulrike and Lalk, Michael
and Langer, Peter and Lindequist, Ulrike and Hecker, Michael and
Antelmann, Haike},
title = {Transcriptome and proteome analyses in response to 2-methylhydroquinone
and 6-brom-2-vinyl-chroman-4-on reveal different degradation systems
involved in the catabolism of aromatic compounds in Bacillus subtilis},
journal = {Proteomics},
year = {2007},
volume = {7},
pages = {1391--1408},
number = {9},
abstract = {Abstract 10.1002/pmic.200700008.abs Bacillus subtilis is exposed to
a variety of antimicrobial compounds in the soil. In this paper,
we report on the response of B. subtilis to the fungal-related antimicrobials
6-brom-2-vinyl-chroman-4-on (chromanon) and 2-methylhydroquinone
(2-MHQ) using proteome and transcriptome analyses. Chromanon, a derivative
of aposphaerins from Aposphaeria species caused predominant protein
damage in B. subtilis as indicated by the induction of the HrcA,
CtsR, and Spx regulons. The expression profile of the ganomycin-related
substance 2-MHQ was similar to that of catechol as reflected by the
common induction of the thiol-specific oxidative stress response.
Several putative ring-cleavage dioxygenases and oxidoreductases were
differentially up-regulated by 2-MHQ, catechol, and chromanon including
yfiDE, ydfNOP, yodED, ycnDE, yodC, and ykcA. The nitroreductase encoding
yodC gene is induced in response to catechol, 2-MHQ, and chromanon,
which depend on the MarR-type repressor YodB. The yfiDE (catDE) operon
encodes a catechol-2,3-dioxygenase which is most strongly induced
by catechol. The yodED (mhqED), ydfNOP (mhqNOP) operons, and ykcA
(mhqA) respond most strongly to 2-MHQ and encode putative hydroquinone-specific
extradiol dioxygenases. The ycnDE operon was most strongly induced
by chromanon. Mutational analyses revealed that the putative hydroquinone-specific
dioxygenases MhqO and MhqA confer resistance to 2-MHQ in B. subtilis.},
issn = {1615-9861},
keywords = {2-Methylhydroquinone, Bacillus subtilis, Chromanon, Extradiol dioxygenases,
YodB},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200700008}
}
@ARTICLE{VanGramberg2010,
author = {Van Gramberg, A. and Beavis, A. and Doble, P. and Mileham, S.},
title = {Optimisation of the separation of amphetamine-type stimulants using
artificial neural networks for applications on lab-on-a-chip technology},
journal = {Science \& Justice},
year = {2010},
volume = {50},
pages = {41--41},
number = {1},
month = mar,
booktitle = {Special Issue: 5th Triennial Conference of the European Academy of
Forensic Science - Knowledge, Research and Leadership in Forensic
Science},
issn = {1355-0306},
url = {http://www.sciencedirect.com/science/article/B8G40-4YHBPC7-1R/2/cbca1c0136505422f10323b4fb262ca5}
}
@ARTICLE{VanHiel2009,
author = {Van Hiel, Matthias and Van Wielendaele, Pieter and Temmerman, Liesbet
and Van Soest, Sofie and Vuerinckx, Kristel and Huybrechts, Roger
and Broeck, Jozef and Simonet, Gert},
title = {Identification and validation of housekeeping genes in brains of
the desert locust Schistocerca gregaria under different developmental
conditions},
journal = {BMC Molecular Biology},
year = {2009},
volume = {10},
pages = {56},
number = {1},
abstract = {BACKGROUND:To obtain reliable quantitative RT-PCR data, normalization
relative to stable housekeeping genes is required. However, in practice,
expression levels of 'typical' housekeeping genes have been found
to vary between tissues and under different experimental conditions.
To date, validation studies of reference genes in insects are extremely
rare and have never been performed in locusts. In this study, putative
housekeeping genes were identified in the desert locust, Schistocerca
gregaria and two different software programs (geNorm and Normfinder)
were applied to assess the stability of thesegenes.RESULTS:We have
identified seven orthologs of commonly used housekeeping genes in
the desert locust. The selected genes were the orthologs of actin,
EF1a, GAPDH, RP49, TubA1, Ubi, and CG13220. By employing real time
RT-PCR we have analysed the expression of these housekeeping genes
in brain tissue of fifth instar nymphs and adults. In the brain of
fifth instar nymphs geNorm indicated Sg-EF1a, Sg-GAPDH and Sg-RP49
as most stable genes, while Normfinder ranked Sg-RP49, Sg-EF1a and
Sg-ACT as most suitable candidates for normalization. The best normalization
candidates for gene expression studies in the brains of adult locusts
were Sg-EF1a, Sg-GAPDH and Sg-Ubi according to geNorm, while Normfinder
determined Sg-GAPDH, Sg-Ubi and Sg-ACT as the most stable housekeeping
genes.CONCLUSION:To perform transcript profiling studies on brains
of the desert locust, the use of Sg-RP49, Sg-EF1a and Sg-ACT as reference
genes is proposed for studies of fifth instar nymphs. In experiments
with adult brains, however, the most preferred reference genes were
Sg-GAPDH, Sg-Ubi and Sg-EF1a. These data will facilitate transcript
profiling studies in desert locusts and provide a good starting point
for the initial selection of genes for validation studies in other
insects.},
doi = {10.1186/1471-2199-10-56},
issn = {1471-2199},
pubmedid = {19508726},
url = {http://www.biomedcentral.com/1471-2199/10/56}
}
@ARTICLE{VanLa2007,
author = {Van La, My and Barbry, Pascal and Raoult, Didier and Renesto, Patricia},
title = {Molecular basis of Tropheryma whipplei doxycycline susceptibility
examined by transcriptional profiling},
journal = {J. Antimicrob. Chemother.},
year = {2007},
volume = {59},
pages = {370--377},
number = {3},
month = mar,
abstract = {Objectives and methodsTropheryma whipplei is a poorly studied bacterium
responsible for Whipple's disease. In this study, its susceptibility
to doxycycline was investigated at a transcriptional level using
a whole-genome DNA microarray. ResultsExposure of T. whipplei to
the MIC of doxycycline (0.5 mg/L) induced antibiotic-specific primary
expression profiles, while indirect effects were detected at 10 x
MIC. In contrast to what was observed for several microorganisms
exposed to antibiotics, the heat-shock proteins were not affected.
Consistent with the mode of action of this translation inhibitor,
genes encoding for ribosomal proteins and translation factors were
differentially transcribed. This analysis also evidenced the regulation
of genes that should account for cell growth arrest. Long-term survival
of non-replicating bacteria is likely to be ensured by an increased
level of ppGpp, the nucleotide effector of the stringent response.
The gene expression profile observed with 10 x MIC was mainly characterized
by the up-regulation of ABC transporters that possibly form efflux
and detoxification systems, through which T. whipplei may limit the
effects of this bacteriostatic compound. Obtained microarray data
showed good agreement with real-time quantitative PCR (R2 = 0.969).
ConclusionsThis work represents the first comprehensive genomic approach
providing insights into the expression signature triggered by the
exposure of T. whipplei to antibiotics.},
url = {http://jac.oxfordjournals.org/cgi/content/abstract/59/3/370}
}
@ARTICLE{VanLaere2004,
author = {Van Laere, Steven J. and Van Den Eynden, Gert G. and Van der Auwera,
Ilse and Elst, Hilde J. and Benoy, Ina and Fox, Stephen B. and Harris,
Adrian L. and Colpaert, Cecile G. and Van Dam, Peter and Van Marck,
Eric A. and Vermeulen, Peter B. and Dirix, Luc Y.},
title = {Unsupervised hierarchical clustering of gene expression level data
obtained by microarray analysis demonstrated a unique expression
pattern for inflammatory breast cancer versus non-inflammatory breast
cancer},
journal = {AACR Meeting Abstracts},
year = {2004},
volume = {2004},
pages = {1210--},
number = {1},
month = mar,
abstract = {Inflammatory Breast Cancer ( IBC ) is a specific type of breast cancer
with unique clinical and pathological features. Approximately 6%
of all breast cancer patients suffer from IBC. IBC is very aggressive
and highly metastatic. Despite a high lethality and the fact that
IBC is clinically well characterised, little is known about the parameters
that determine the rapid progression of the disease. Several studies
indicate an increase in angiogenic activity when comparing IBC with
non-IBC. The aim of this study was to investigate whether a difference
between IBC and non-IBC was present based on gene expression profiling.
RNA extracted from 17 IBC and 22 non-IBC patient was used. The RNA
concentration and the purity ( A260/A280 ) was measured spectrophotometrically.
The quality ( 28S/18S ) was assessed using the Agilent Bioanalyzer
2100. RNA with high concentration ( >100ug/mL ) , high purity ( A260/A280
> 1.8 ) and high quality ( 28S/18S > 2.0 ) was used for microarray
experiments. These experiments were conducted at the Nuffield Department
of Clinical Laboratory Sciences, John Radcliffe Hospital, Headington
Oxford. cDNA slides were obtained from the Sanger Institute ( Hver1.2.1
). This slide contains 10752 cDNA fragments derived from various
collections. Before hybridisation, RNA was amplified and labelled
using the Ambion Amino Allyl MessageAmp aRNA Amplification Kit. RNA
from each patient was hybridised individually against a reference
( Universal Human Reference RNA, Stratagene ). Patient RNA was labelled
with Cy5, reference RNA was labelled with Cy3. Hybridisation was
executed following the Sanger Institute protocol. The slides were
scanned and analysed using three different software programs: ScanArray,
Quantarray and GeneSpring. We compared the gene expression data from
IBC with those from non-IBC. We calculated a Fold Ratio ( FR ) by
dividing the gene expression data from IBC by the gene expression
data from non-IBC. When the FR was greater then 2 we considered the
gene as being overexpressed in IBC. When the FR was less then 0.5
we considered the gene as being repressed in IBC. Additionally we
analysed a list with genes that were 1.5 times more expressed in
IBC when compared with non-IBC. We found approximately 100 genes
overexpressed in IBC and an equal amount repressed. About 800 genes
were 1.5 times more expressed in IBC when compared to non-IBC. Genes
involved in cell migration, cell adhesion, angiogenesis and inflammation
were found to be more expressed in IBC. This study corroborates the
unique clinical and pathological phenotype of IBC by genome-wide
cDNA microarray analysis. Furthermore, the study provides insight
in the pathways involved in the aggressive biology of IBC.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/1210}
}
@ARTICLE{VanLangendonckt2007,
author = {Van Langendonckt, A. and Punyadeera, C. and Kamps, R. and Dunselman,
G. and Klein-Hitpass, L. and Schurgers, L.J. and Squifflet, J. and
Donnez, J. and Groothuis, P.},
title = {Identification of novel antigens in blood vessels in rectovaginal
endometriosis},
journal = {Mol. Hum. Reprod.},
year = {2007},
volume = {13},
pages = {875--886},
number = {12},
month = dec,
abstract = {To identify specific markers of rectovaginal endometriotic nodule
vasculature, highly enriched preparations of vascular endothelial
cells and pericytes were obtained from endometriotic nodules and
control endometrial and myometrial tissue by laser capture microdissection
(LCM), and gene expression profiles were screened by microarray analysis.
Of the 18 400 transcripts on the arrays, 734 were significantly overexpressed
in vessels from fibromuscular tissue and 923 in vessels from stromal
tissue of endometriotic nodules, compared with vessels dissected
from control tissues. The most frequently expressed transcripts included
known endothelial cell-associated genes, as well as transcripts with
little or no previous association with vascular cells. The higher
expression in blood vessels was further corroborated by immunohistochemical
staining of six potential markers, five of which showed strong expression
in pericytes. The most promising marker was matrix Gla protein, which
was found to be present in both glandular epithelial cells and vascular
endothelial cells of endometriotic lesions, although it was barely
expressed at all in normal endometrium. LCM, combined with microarray
analysis, constitutes a powerful tool for mapping the transcriptome
of vascular cells. After immunohistochemical validation, markers
of vascular endothelial and perivascular cells from endometriotic
nodules could be identified, which may provide targets to improve
early diagnosis or to selectively deliver therapeutic agents.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/13/12/875}
}
@ARTICLE{VanLommel2006,
author = {Van Lommel, Leentje and Janssens, Kristel and Quintens, Roel and
Tsukamoto, Katsura and Vander Mierde, Dirk and Lemaire, Katleen and
Denef, Carl and Jonas, Jean-Christophe and Martens, Geert and Pipeleers,
Daniel and Schuit, Frans C.},
title = {Probe-Independent and Direct Quantification of Insulin mRNA and Growth
Hormone mRNA in Enriched Cell Preparations},
journal = {Diabetes},
year = {2006},
volume = {55},
pages = {3214--3220},
number = {12},
month = dec,
abstract = {Task division in multicellular organisms ensures that differentiated
cell types produce cell-specific proteins that fulfill tasks for
the whole organism. In some cases, the encoded mRNA species is so
abundant that it represents a sizeable fraction of total mRNA in
the cell. In this study, we have used a probe- and primer-free technique
to quantify such abundant mRNA species in order to assess regulatory
effects of in vitro and in vivo conditions. As a first example, we
were able to quantify the regulation of proinsulin mRNA abundance
in {beta}-cells by food intake or by the glucose concentration in
tissue culture. The second example of application of this technique
is the effect of corticosteroids on growth hormone mRNA in enriched
somatrotrophs. It is anticipated that other examples exist in which
measurement of very abundant mRNAs in dedicated cells will help to
understand biological processes, monitor disease states, or assist
biotechnological manufacturing procedures.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/55/12/3214}
}
@ARTICLE{VanNoorden2011,
author = {Van Noorden, Susan and Lampert, Irvin A. and Xue, Shao-An and Lykidis,
Dimitrios and Phillips, John A. and Molyneux, Elizabeth and Griffin,
Beverly E.},
title = {Burkitt's lymphoma: maximising the use of fine needle aspirates by
long-term preservation for diagnosis and research},
journal = {Transactions of the Royal Society of Tropical Medicine and Hygiene},
year = {2011},
volume = {105},
pages = {86--94},
number = {2},
month = feb,
abstract = {Summary Fine needle aspirates from Burkitt's lymphoma and other tumours
transferred directly into ThinPrep® PreservCyt® (Cytyc UK Ltd, Crawley,
UK) buffered alcohol fixative retain their cellular and viral antigens
and nucleic acids for many months at ambient temperatures. Despite
the presence of blood and debris, cells dried onto slides from droplets
and post-fixed in formalin, or sections of paraffin-embedded cell
blocks from formalin post-fixed pellets, prove adequate for morphology,
immunocytochemistry, in-situ hybridization and molecular biological
analyses. Where there is lack of expertise in making thin smears
or hospitals lack pathology laboratories and services, PreservCyt®
provides an excellent medium for transport elsewhere for diagnosis
and research.},
issn = {0035-9203},
keywords = {African childhood tumours. Fine needle aspirate. Cytological fixative.
Transport medium. Immunocytochemistry. EBV gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0035920310002397}
}
@ARTICLE{VanPeer2010,
author = {Van Peer, Arend F. and Wang, Fengfeng and Van Driel, Kenneth G. A.
and De Jong, Jan F. and Van Donselaar, Elly G. and Müller, Wally
H. and Boekhout, Teun and Lugones, Luis G. and Wösten, Han A. B.},
title = {The septal pore cap is an organelle that functions in vegetative
growth and mushroom formation of the wood-rot fungus Schizophyllum
commune},
journal = {Environmental Microbiology},
year = {2010},
volume = {12},
pages = {833--844},
number = {4},
abstract = {Summary Mushroom-forming basidiomycetes colonize large areas in nature.
Their hyphae are compartmentalized by perforated septa, which are
usually covered by a septal pore cap (SPC). Here, we describe, for
the first time, the composition and function of SPCs using the model
system Schizophyllum commune. The SPC of S. commune was shown to
consist of a proteinaceous matrix covered by a lipid membrane. The
matrix was demonstrated to define the ultrastructure of the SPC and
to consist of two main proteins, Spc14 and Spc33. Gene spc14 encodes
a protein of 86 amino acids, which lacks known domain, signal or
localization sequences. Gene spc33 encodes a 239 and a 340 amino
acid variant. Both forms contain a predicted signal anchor that targets
them to the ER. Immuno-localization showed the presence of Spc33
in the SPC but not in ER. From this and previous reports it is concluded
that the SPC is derived from this organelle. Inactivation of spc33
resulted in loss of SPCs and the inability to close septa. The latter
may well explain why vegetative growth and mushroom formation were
severely reduced in strains in which spc33 was inactivated.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2009.02122.x}
}
@ARTICLE{VanSchijndel2010,
author = {Van Schijndel, Jessica E. and Van Zweeden, Martine and Van Loo, Karen
M.J. and Martens, Gerard J.M.},
title = {Gene expression profiling in brain regions of a rat model displaying
schizophrenia-related features},
journal = {Behavioural Brain Research},
year = {2010},
volume = {207},
pages = {476--479},
number = {2},
month = mar,
abstract = {Animal models allow insights into complex neurodevelopmental disorders.
Apomorphine-susceptible rats (so-called APO-SUS rats) provide a model
that displays a complex phenotype with schizophrenia-related features
and together with its phenotypic counterpart (APO-UNSUS rats) has
been independently generated twice (original and replicate rat lines).
To understand the molecular basis underlying this phenotype, we here
performed mRNA expression profiling in various APO-SUS and APO-UNSUS
rat brain regions. The expression of only the previously reported
Aph-1b and the newly discovered KCnIP1 (a member of the potassium
channel-interacting protein family that is known to modulate neuronal
channel activity) was significantly different in the APO-SUS and
APO-UNSUS rats from both the original and replicate rat lines. Thus,
KCnIP1 may constitute a novel candidate gene playing a role in the
complex phenotype of the APO-SUS/APO-UNSUS rat model and further
studies on this gene are warranted.},
issn = {0166-4328},
keywords = {Apomorphine-(un)susceptible rats, Complex phenotype, Schizophrenia,
Dopamine, Microarray, Potassium channel-interacting protein 1, Rat
brain},
url = {http://www.sciencedirect.com/science/article/B6SYP-4XMKB2K-1/2/8deee4439deae7ea72e3978531ff787b}
}
@ARTICLE{VanVaerenbergh2011,
author = {Van Vaerenbergh, Inge and Blockeel, Christophe and Van Lommel, Leentje
and Ghislain, Vanessa and In't Veld, Peter and Schuit, Frans and
Fatemi, Human Mousavi and Devroey, Paul and Bourgain, Claire},
title = {Cyclooxygenase-2 network as predictive molecular marker for clinical
pregnancy in in vitro fertilization},
journal = {Fertility and Sterility},
year = {2011},
volume = {95},
pages = {448--451.e2},
number = {1},
month = jan,
abstract = {The gene expression of human endometrium on the day of oocyte retrieval
of pregnant and nonpregnant patients in a stimulated IVF cycle was
compared in two independent groups with different GnRH-antagonist
ovarian stimulation protocols. The present data suggest that increased
gene expression of cyclooxygenase-2, together with the expression
of other molecules in the cyclooxygenase-2 network, on the day of
oocyte retrieval in GnRH-antagonist cycles coincides with a lower
probability of achieving a clinical pregnancy in this cycle.},
issn = {0015-0282},
keywords = {Microarray, endometrial receptivity, clinical pregnancy, molecular
marker, GnRH antagonists},
url = {http://www.sciencedirect.com/science/article/pii/S0015028210021679}
}
@ARTICLE{VanVaerenbergh2009,
author = {Van Vaerenbergh, Inge and Van Lommel, Leentje and Ghislain, Vanessa
and In't Veld, Peter and Schuit, Frans and Fatemi, Human Mousavi
and Devroey, Paul and Bourgain, Claire},
title = {In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial
maturation on the day of oocyte retrieval correlates with altered
gene expression},
journal = {Hum. Reprod.},
year = {2009},
volume = {24},
pages = {1085--1091},
number = {5},
month = may,
abstract = {BACKGROUNDPreviously, advanced endometrial maturation on the day of
oocyte retrieval in GnRH antagonist and -agonist IVF cycles was observed.
In these cycles, endometrial advancement exceeding 3 days between
the histological dating and the cycle day never resulted in an ongoing
clinical pregnancy. In this study, the gene expression of human endometrium
on the day of oocyte retrieval in GnRH antagonist/rec-FSH cycles
was analyzed, in correlation with the morphological dating. METHODSBiopsies
were taken on the day of oocyte retrieval in 47 patients with 1 or
2 embryos replaced on Day 3 in the same cycle. Endometrial dating
was performed according to Noyes' criteria. Biopsies from 11 patients
were analyzed for gene expression with the Affymetrix HG U133 Plus
2 microarray. Data analysis, clustering and pathway analysis were
performed with GCOS, GeneSpring 7.3 and Ingenuity, respectively.
RESULTSAccording to Noyes' criteria, all endometria taken on the
day of oocyte retrieval showed an advanced maturation, ranging from
+d2 to +d4. The patients with a subsequent clinical pregnancy all
showed a histological dating corresponding to +d2 or +d3. When comparing
endometria +d2-3 to +d4, the microarray results showed a differential
expression of 2550 probe sets. Significantly up-regulated genes were
SERPINB6, FOXO3A, SOX17 and CDC42. Down-regulated genes of interest
were NRP1, HOXA10 and OSF2. Principal component analysis and hierarchical
clustering demonstrated two distinct clusters. CONCLUSIONSIn stimulated
cycles, endometrial gene expression on the day of oocyte retrieval
discriminates between women with and without histologically advanced
endometrial maturation exceeding 3 days and supports histological
dating results by Noyes' criteria.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/24/5/1085}
}
@ARTICLE{Vanaja2003,
author = {Vanaja, Donkena Krishna and Cheville, John C. and Iturria, Steve
J. and Young, Charles Y. F.},
title = {Transcriptional Silencing of Zinc Finger Protein 185 Identified by
Expression Profiling Is Associated with Prostate Cancer Progression},
journal = {Cancer Res.},
year = {2003},
volume = {63},
pages = {3877--3882},
number = {14},
month = jul,
abstract = {We profiled the expression of genes in benign and untreated human
prostate cancer tissues using oligonucleotide microarrays. We report
here 50 genes with distinct expression patterns in metastatic and
confined tumors (Gleason score 6 and 9; lymph node invasive and noninvasive).
Validation of expression profiles of 6 genes by quantitative PCR
revealed a strong inverse correlation in the expression of zinc finger
protein 185 (ZNF185), bullous pemphigoid antigen gene (BPAG1), and
prostate secretory protein (PSP94) with progression of prostate cancer.
Treatment of prostate cancer cell lines with 5-aza-2'-deoxycytidine
(5-Aza-CdR), an inhibitor of DNA methylation, restored ZNF185 expression
levels. Moreover, methylation-specific PCR confirmed methylation
of the 5'CpG islands of the ZNF185 gene in all of the metastatic
tissues and 44% of the localized tumor tissues, as well as in the
prostate cancer cell lines tested. Thus, transcriptional silencing
of ZNF185 by methylation in prostate tumor tissues implicates the
ZNF185 gene in prostate tumorigenesis.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/63/14/3877}
}
@ARTICLE{Vanasse2004,
author = {Vanasse, Gary J. and Winn, Robert K. and Rodov, Sofya and Zieske,
Arthur W. and Li, John T. and Tupper, Joan C. and Tang, Jingjing
and Raines, Elaine W. and Peters, Mette A. and Yeung, Ka Yee and
Harlan, John M.},
title = {Bcl-2 Overexpression Leads to Increases in Suppressor of Cytokine
Signaling-3 Expression in B Cells and De novo Follicular Lymphoma},
journal = {Mol. Cancer Res.},
year = {2004},
volume = {2},
pages = {620--631},
number = {11},
month = nov,
abstract = {The t(14;18)(q32;q21), resulting in deregulated expression of B-cell-leukemia/lymphoma-2
(Bcl-2), represents the genetic hallmark in human follicular lymphomas.
Substantial evidence supports the hypothesis that the t(14;18) and
Bcl-2 overexpression are necessary but not solely responsible for
neoplastic transformation and require cooperating genetic derangements
for neoplastic transformation to occur. To investigate genes that
cooperate with Bcl-2 to influence cellular signaling pathways important
for neoplastic transformation, we used oligonucleotide microarrays
to determine differential gene expression patterns in CD19+ B cells
isolated from E{micro}-Bcl-2 transgenic mice and wild-type littermate
control mice. Fifty-seven genes were induced and 94 genes were repressed
by [≥]2-fold in E{micro}-Bcl-2 transgenic mice (P < 0.05). The
suppressor of cytokine signaling-3 (SOCS3) gene was found to be overexpressed
5-fold in B cells from E{micro}-Bcl-2 transgenic mice. Overexpression
of Bcl-2 in both mouse embryo fibroblast-1 and hematopoietic cell
lines resulted in induction of SOCS3 protein, suggesting a Bcl-2-associated
mechanism underlying SOCS3 induction. Immunohistochemistry with SOCS3
antisera on tissue from a cohort of patients with de novo follicular
lymphoma revealed marked overexpression of SOCS3 protein that, within
the follicular center cell region, was limited to neoplastic follicular
lymphoma cells and colocalized with Bcl-2 expression in 9 of 12 de
novo follicular lymphoma cases examined. In contrast, SOCS3 protein
expression was not detected in the follicular center cell region
of benign hyperplastic tonsil tissue. These data suggest that Bcl-2
overexpression leads to the induction of activated signal transducer
and activator of transcription 3 (STAT3) and to the induction of
SOCS3, which may contribute to the pathogenesis of follicular lymphoma.},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/2/11/620}
}
@ARTICLE{VanBuren2011,
author = {VanBuren, Peter and Ma, Jun and Chao, Samuel and Mueller, Enkhtuyaa
and Schneider, David J. and Liew, Choong-Chin},
title = {Blood gene expression signatures associate with heart failure outcomes},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {392--397},
number = {8},
month = apr,
abstract = {Gene expression signatures in blood correlate with specific diseases.
Such signatures may serve as valuable diagnostic and prognostic tools
in disease management. Blood gene expression signatures associated
with heart failure may be applied to predict prognosis, monitor disease
progression, and optimize treatment. Blood gene expression profiles
were generated for 71 subjects with heart failure and 15 controls
without heart failure, using the Affymetrix GeneChip U133Plus2.0.
Survival analysis identified 197 "mortality genes" that were significantly
associated with patient outcome. Functional categorization showed
that genes associated with T cell receptor signaling were most significantly
overpresented. Cluster analysis of these T cell receptor signaling
genes significantly categorized heart failure patients into three
risk groups (P = 0.031) that were distinct from the three risk groups
categorized by New York Heart Association (NYHA) Classification (P
= 0.0002). By combining the analysis of clinical assessment (NYHA
class) with T cell receptor signaling gene expression, we proposed
a model that demonstrated an even greater differentiation of patients
at risk (P = 0.0001). In this discovery study, we identified blood
expression signatures associated with heart failure patient outcomes.
Characterization of these mortality genes helped identify a set of
T cell receptor signaling genes that may be of utility in predicting
survival of heart failure patients. These data raise the possibility
of prospectively risk stratifying patients with heart failure by
integrating blood gene expression signatures with current clinical
assessment.},
comment = {10.1152/physiolgenomics.00175.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/8/392}
}
@ARTICLE{Vance2010,
author = {Vance, Keith W. and Shaw, Heather M. and Rodriguez, Mercedes and
Ott, Sascha and Goding, Colin R.},
title = {The Retinoblastoma Protein Modulates Tbx2 Functional Specificity},
journal = {Mol. Biol. Cell},
year = {2010},
volume = {21},
pages = {2770--2779},
number = {15},
month = aug,
abstract = {Tbx2 is a member of a large family of transcription factors defined
by homology to the T-box DNA-binding domain. Tbx2 plays a key role
in embryonic development, and in cancer through its capacity to suppress
senescence and promote invasiveness. Despite its importance, little
is known of how Tbx2 is regulated or how it achieves target gene
specificity. Here we show that Tbx2 specifically associates with
active hypophosphorylated retinoblastoma protein (Rb1), a known regulator
of many transcription factors involved in cell cycle progression
and cellular differentiation, but not with the Rb1-related proteins
p107 or p130. The interaction with Rb1 maps to a domain immediately
carboxy-terminal to the T-box and enhances Tbx2 DNA binding and transcriptional
repression. Microarray analysis of melanoma cells expressing inducible
dominant-negative Tbx2, comprising the T-box and either an intact
or mutated Rb1 interaction domain, shows that Tbx2 regulates the
expression of many genes involved in cell cycle control and that
a mutation which disrupts the Rb1-Tbx2 interaction also affects Tbx2
target gene selectivity. Taken together, the data show that Rb1 is
an important determinant of Tbx2 functional specificity.},
url = {http://www.molbiolcell.org/cgi/content/abstract/21/15/2770}
}
@ARTICLE{Vandamme2011,
author = {Vandamme, Katleen and Holy, Xavier and Bensidhoum, Morad and Logeart-Avramoglou,
Delphine and Naert, Ignace E. and Duyck, Joke A. and Petite, Hervé},
title = {In vivo molecular evidence of delayed titanium implant osseointegration
in compromised bone},
journal = {Biomaterials},
year = {2011},
volume = {32},
pages = {3547--3554},
number = {14},
month = may,
abstract = {Optimization of implant osseointegration in patients with reduced
bone healing potential is a challenge remaining in implant dentistry.
Identification of the genes that are modulated during implant osseointegration
in normal versus osteopenic bone is needed to successfully address
these pertinent clinical needs. The present study aimed to assess
the initial and early molecular events following titanium implant
installation in normal and compromised bone in a rat tibia model.
Peri-implant tissue from a well-defined tissue regeneration compartment
was analyzed at 2 and 7 days post-surgery for the expression of select
markers of inflammation, angiogenesis, bone resorption and bone formation.
Impaired bone was induced by hindlimb unloading and validated using
[mu]CT. The essential step of angiogenesis preceding bone regeneration
was evidenced for the peri-implant setting in healthy bone. Compromised
bone significantly affected the angiogenesis-osteogenesis coupling
in the initial phase (2 days post-surgery), with altered expressions
of Vegfa and Epas1 coinciding with downregulated expressions of Col1a1,
Bmp2, Bmp4, Alpl and Bglap. At 7 days post-implantation, differences
between normal and compromised peri-implant bone were no longer observed.
This in vivo molecular evidence of delayed implant osseointegration
in compromised bone reassert modern strategies in implant development,
such as surface modifications and bioengineered approaches, to improve
implant osseointegration in compromised conditions.},
issn = {0142-9612},
keywords = {Titanium, Implant, Osseointegration, Bone, Gene expression, Animal
model},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211000883}
}
@ARTICLE{Vandebriel2010,
author = {Vandebriel, Rob J. and Pennings, Jeroen L. A. and Baken, Kirsten
A. and Pronk, Tessa E. and Boorsma, Andre and Gottschalk, Ralph and
Van Loveren, Henk},
title = {Keratinocyte Gene Expression Profiles Discriminate Sensitizing and
Irritating Compounds},
journal = {Toxicol. Sci.},
year = {2010},
volume = {117},
pages = {81--89},
number = {1},
month = sep,
abstract = {Many chemicals can induce allergic contact dermatitis. Because evaluation
of skin sensitizing potential by animal testing is prohibited for
cosmetics, and screening of many chemicals is required within Registration,
Evaluation, Authorisation and Restriction of Chemicals, urgent need
exists for predictive in vitro assays to identify contact allergens.
Keratinocytes (KC) are the first cells encountered when chemicals
land on the skin. Therefore, KC form an important site of haptenization
and their metabolism is likely to be important. Moreover, KC secrete
mediators that affect processing and presentation of haptenized proteins
by dendritic cells. To develop a KC-based in vitro assay to predict
sensitizing potential of chemicals, in vitro exposure effects of
eight contact sensitizers and six irritants on the KC cell line HaCaT
were examined by gene profiling. Classifiers predictive of the class
sensitizers or irritants were calculated, based on support vector
machine (SVM) and random forest (RF) algorithms. Classifiers using
high-ranking genes were 70% (SVM) and 62% (RF) accurate, based on
three (SVM) and two to five (RF) features. Classifiers using oxidative
stress pathway gene sets were 68-73% (SVM) and 69-71% (RF) accurate.
Cross-validation showed that the top-3 of most discriminating genes
added up to 13 genes and included oxidative stress gene HMOX1 irrespective
of the chemical left out. Moreover, HMOX1 was the most significantly
regulated gene. Gene Set Enrichment Analysis showed upregulation
of "Keap1 dependent" and "oxidative stress" gene lists. In conclusion,
KC expression profiling can identify contact sensitizers, providing
opportunities for nonanimal testing for sensitizing potential. Moreover,
our data suggest that contact sensitizers induce the oxidative stress
pathway in KC.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/117/1/81}
}
@ARTICLE{Vandenhove2010,
author = {Vandenhove, Hildegarde and Vanhoudt, Nathalie and Cuypers, Ann and
van Hees, May and Wannijn, Jean and Horemans, Nele},
title = {Life-cycle chronic gamma exposure of Arabidopsis thaliana induces
growth effects but no discernable effects on oxidative stress pathways},
journal = {Plant Physiology and Biochemistry},
year = {2010},
volume = {48},
pages = {778--786},
number = {9},
month = sep,
abstract = {Arabidopsis thaliana was exposed to low-dose chronic gamma irradiation
during a full life cycle (seed to seed) and several biological responses
were investigated. Applied dose rates were 2336, 367 and 81 [mu]Gy h-1.
Following 24 days (inflorescence emergence), 34 days (~50% of flowers
open) and 54 days (silice ripening) exposure, plants were harvested
and monitored for biometric parameters, capacities of enzymes involved
in the antioxidative defence mechanisms (SOD, APOD, GLUR, GPOD, SPOD,
CAT, ME), glutathione and ascorbate pool, lipid peroxidation products,
altered gene expression of selected genes encoding for antioxidative
enzymes or reactive oxygen species production, and DNA integrity.
Root fresh weight was significantly reduced after gamma exposure
compared to the control at all stages monitored but no significant
differences in root weight for the different dose rates applied was
observed. Leaf and stem fresh weight were significantly reduced at
the highest irradiation level after 54 days exposure only. Also total
plant fresh was significantly lower at silice riping and this for
the highest and medium dose rate applied. The dose rate estimated
to result in a 10% reduction in growth (EDR-10) ranged between 60
and 80 [mu]Gy h-1. Germination of seeds from the gamma irradiated
plants was not hampered. For several of the antioxidative defence
enzymes studied, the enzyme capacity was generally stimulated towards
flowering but generally no significant effect of dose rate on enzyme
capacity was observed. Gene analysis revealed a significant transient
and dose dependent change in expression of RBOHC indicating active
reactive oxygen production induced by gamma irradiation. No effect
of irradiation was observed on concentration or reduction state of
the non-enzymatic antioxidants, ascorbate and glutathione. The level
of lipid peroxidation products remained constant throughout the observation
period and was not affected by dose rate. The comet assay did not
reveal any effect of gamma dose rate on DNA integrity.},
issn = {0981-9428},
keywords = {Arabidopsis thaliana, Chronic gamma exposure, Oxidative stress response},
url = {http://www.sciencedirect.com/science/article/B6VRD-50CV7VJ-1/2/14673dc6f717067030e59a5b4d51b7b2}
}
@ARTICLE{Vandeputte2011,
author = {Vandeputte, Olivier M. and Kiendrebeogo, Martin and Rasamiravaka,
Tsiry and Stevigny, Caroline and Duez, Pierre and Rajaonson, Sanda
and Diallo, Billo and Mol, Adeline and Baucher, Marie and El Jaziri,
Mondher},
title = {The flavanone naringenin reduces the production of quorum sensing-controlled
virulence factors in Pseudomonas aeruginosa PAO1},
journal = {Microbiology},
year = {2011},
volume = {157},
pages = {2120-2132},
number = {7},
abstract = {Preliminary screening of the Malagasy plant Combretum albiflorum for
compounds attenuating the production of quorum sensing (QS)-controlled
virulence factors in bacteria led to the identification of active
fractions containing flavonoids. In the present study, several flavonoids
belonging to the flavone, flavanone, flavonol and chalcone structural
groups were screened for their capacity to reduce the production
of QS-controlled factors in the opportunistic pathogen Pseudomonas
aeruginosa (strain PAO1). Flavanones (i.e. naringenin, eriodictyol
and taxifolin) significantly reduced the production of pyocyanin
and elastase in P. aeruginosa without affecting bacterial growth.
Consistently, naringenin and taxifolin reduced the expression of
several QS-controlled genes (i.e. lasI, lasR, rhlI, rhlR, lasA, lasB,
phzA1 and rhlA) in P. aeruginosa PAO1. Naringenin also dramatically
reduced the production of the acylhomoserine lactones N-(3-oxododecanoyl)-L-homoserine
lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL),
which is driven by the lasI and rhlI gene products, respectively.
In addition, using mutant strains deficient for autoinduction ({Delta}lasI
and {Delta}rhlI) and LasR- and RhlR-based biosensors, it was shown
that QS inhibition by naringenin not only is the consequence of a
reduced production of autoinduction compounds but also results from
a defect in the proper functioning of the RlhR-C4-HSL complex. Widely
distributed in the plant kingdom, flavonoids are known for their
numerous and determinant roles in plant physiology, plant development
and in the success of plant-rhizobia interactions, but, as shown
here, some of them also have a role as inhibitors of the virulence
of pathogenic bacteria by interfering with QS mechanisms.},
doi = {10.1099/mic.0.049338-0},
eprint = {http://mic.sgmjournals.org/cgi/reprint/157/7/2120.pdf},
url = {http://mic.sgmjournals.org/cgi/content/abstract/157/7/2120}
}
@ARTICLE{Vanderauwera2007,
author = {Vanderauwera, Sandy and De Block, Marc and Van de Steene, Nancy and
van de Cotte, Brigitte and Metzlaff, Michael and Van Breusegem, Frank},
title = {Silencing of poly(ADP-ribose) polymerase in plants alters abiotic
stress signal transduction},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {15150--15155},
number = {38},
month = sep,
abstract = {Transgenic plants with reduced poly(ADP-ribose) polymerase (PARP)
levels have broad-spectrum stress-resistant phenotypes. Both Arabidopsis
thaliana and oilseed rape (Brassica napus) lines overexpressing RNA
interference-PARP constructs were more resistant to various abiotic
stress treatments in laboratory and greenhouse experiments without
negative effects on growth, development, and seed production. This
outperforming stress tolerance was initially attributed solely to
a maintained energy homeostasis due to reduced NAD+ consumption.
We show that in PARP2-deficient Arabidopsis plants, the observed
abiotic stress resistance can also be explained by alterations in
abscisic acid levels that facilitate the induction of a wide set
of defense-related genes.},
url = {http://www.pnas.org/cgi/content/abstract/104/38/15150}
}
@ARTICLE{Vanderauwera2005,
author = {Vanderauwera, Sandy and Zimmermann, Philip and Rombauts, Stephane
and Vandenabeele, Steven and Langebartels, Christian and Gruissem,
Wilhelm and Inze, Dirk and Van Breusegem, Frank},
title = {Genome-Wide Analysis of Hydrogen Peroxide-Regulated Gene Expression
in Arabidopsis Reveals a High Light-Induced Transcriptional Cluster
Involved in Anthocyanin Biosynthesis},
journal = {Plant Physiology},
year = {2005},
volume = {139},
pages = {806--821},
number = {2},
month = oct,
abstract = {In plants, reactive oxygen species and, more particularly, hydrogen
peroxide (H2O2) play a dual role as toxic by-products of normal cell
metabolism and as regulatory molecules in stress perception and signal
transduction. Peroxisomal catalases are an important sink for photorespiratory
H2O2. Using ATH1 Affymetrix microarrays, expression profiles were
compared between control and catalase-deficient Arabidopsis (Arabidopsis
thaliana) plants. Reduced catalase levels already provoked differences
in nuclear gene expression under ambient growth conditions, and these
effects were amplified by high light exposure in a sun simulator
for 3 and 8 h. This genome-wide expression analysis allowed us to
reveal the expression characteristics of complete pathways and functional
categories during H2O2 stress. In total, 349 transcripts were significantly
up-regulated by high light in catalase-deficient plants and 88 were
down-regulated. From this data set, H2O2 was inferred to play a key
role in the transcriptional up-regulation of small heat shock proteins
during high light stress. In addition, several transcription factors
and candidate regulatory genes involved in H2O2 transcriptional gene
networks were identified. Comparisons with other publicly available
transcriptome data sets of abiotically stressed Arabidopsis revealed
an important intersection with H2O2-deregulated genes, positioning
elevated H2O2 levels as an important signal within abiotic stress-induced
gene expression. Finally, analysis of transcriptional changes in
a combination of a genetic (catalase deficiency) and an environmental
(high light) perturbation identified a transcriptional cluster that
was strongly and rapidly induced by high light in control plants,
but impaired in catalase-deficient plants. This cluster comprises
the complete known anthocyanin regulatory and biosynthetic pathway,
together with genes encoding unknown proteins.},
url = {http://www.plantphysiol.org/cgi/content/abstract/139/2/806}
}
@ARTICLE{VanderLugt2009,
author = {VanderLugt, Kyle and Cooney, Michael J. and Lechner, Anna and Lenz,
Petra H.},
title = {Cultivation of the Paracalanid Copepod, Bestiolina similis (Calanoida:
Crustacea)},
journal = {Journal of the World Aquaculture Society},
year = {2009},
volume = {40},
pages = {616--628},
number = {5},
abstract = {Abstract First feed production continues to be a major barrier to
the cultivation of many fish species. Although copepod nauplii are
a suitable food, consistency and high production have been difficult.
Temporal changes in production in batch cultures of the calanoid
copepod, Bestiolina similis, were investigated to develop management
strategies for the use of copepod nauplii as a live food. Population
abundances and female egg production rates were measured, and recruitment
and mortality rates were calculated. Relative expression levels of
a molecular biomarker for stress, heat shock protein hsp70, were
determined using real-time quantitative polymerase chain reaction.
The population cycle included a period of rapid increase in abundances,
followed by a steep decline and a period of stable but low population
densities. Initially, egg production exceeded 25 eggs per female
per day and low mortality rates prevailed. The population decline
was preceded by upregulation of hsp70 and followed by an 80–90%
decline in female fecundity and an increase in mortality rates. Egg
production rates remained below four eggs per female per day even
after new generations of females reached adulthood. The predictable
population cycle provides opportunities to coordinate nauplius production
rates with first feed needs of fish larvae.},
issn = {1749-7345},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1749-7345.2009.00282.x}
}
@ARTICLE{Vanderman2011,
author = {Vanderman, K.S. and Tremblay, M. and Zhu, W. and Shimojo, M. and
Mienaltowski, M.J. and Coleman, S.J. and MacLeod, J.N.},
title = {Brother of CDO (BOC) expression in equine articular cartilage},
journal = {Osteoarthritis and Cartilage},
year = {2011},
volume = {19},
pages = {435--438},
number = {4},
month = apr,
abstract = {Summary Brother of CDO (BOC) is a cell surface receptor that derives
its name from the structurally related protein, cell adhesion molecule-related/down-regulated
by oncogenes (CDO, sometimes CDON). High levels of BOC mRNA and protein
expression have been described in embryonic tissues with active cell
proliferation and ongoing cellular differentiation[1] and [2]. A
microarray-based screen of RNA isolated from 11 different adult equine
tissues unexpectedly identified BOC as having an expression pattern
restricted to articular cartilage. The objective of this study was
to further investigate BOC expression in adult articular cartilage
relative to other tissues. Both RT-qPCR and mRNA sequencing confirmed
the microarray data. Steady state BOC mRNA levels in articular cartilage
were substantially higher than in the other adult tissues tested,
neonatal tendon, placenta, and whole embryo. The expression of BOC
displayed a pattern of tissue specificity comparable to well established
cartilage matrix protein biomarkers. BOC mRNA levels in articular
cartilage increased with age, but were rapidly down-regulated when
chondrocytes were enzymatically isolated from the cartilage matrix
and expanded in monolayer culture. Relative expression patterns of
CDO were broadly similar, but displayed lower fold change differences.
A functional role in articular cartilage that involves Hedgehog signaling
is suggested by the known binding affinity of BOC for all three Hedgehog
ligands. These data also extend BOC and CDO biology to a post-mitotic
and highly differentiated cell type within a mature tissue.},
issn = {1063-4584},
keywords = {BOC, Cartilage, CDO},
url = {http://www.sciencedirect.com/science/article/pii/S1063458411000240}
}
@ARTICLE{VanDersarl2011,
author = {VanDersarl, Jules J. and Xu, Alexander M. and Melosh, Nicholas A.},
title = {Nanostraws for Direct Fluidic Intracellular Access},
journal = {Nano Letters},
year = {2011},
volume = {0},
pages = {null},
number = {0},
abstract = { Nanomaterials are promising candidates to improve the delivery efficiency
and control of active agents such as DNA or drugs directly into cells.
Here we demonstrate cell-culture platforms of nanotemplated “nanostraws�
that pierce the cell membrane, providing a permanent fluidic pipeline
into the cell for direct cytosolic access. Conventional polymeric
track-etch cell culture membranes are alumina coated and etched to
produce fields of nanostraws with controllable diameter, thickness,
and height. Small molecules and ions were successfully transported
into the cytosol with 40 and 70% efficiency, respectively, while
GFP plasmids were successfully delivered and expressed. These platforms
open the way for active, reproducible delivery of a wide variety
of species into cells without endocytosis. },
doi = {10.1021/nl204051v},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/nl204051v},
url = {http://pubs.acs.org/doi/abs/10.1021/nl204051v}
}
@ARTICLE{Vanderschaeghe2010,
author = {Vanderschaeghe, Dieter and SzekreÌ?nyes, AÌ?kos and Wenz, Christian
and Gassmann, Marcus and Naik, Natasha and Bynum, Maggie and Yin,
Hongfeng and Delanghe, Joris and Guttman, Andras and Callewaert,
Nico},
title = {High-Throughput Profiling of the Serum N-Glycome on Capillary Electrophoresis
Microfluidics Systems: Toward Clinical Implementation of GlycoHepatoTest},
journal = {Analytical Chemistry},
year = {2010},
volume = {82},
pages = {7408-7415},
number = {17},
doi = {10.1021/ac101560a},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac101560a},
url = {http://pubs.acs.org/doi/abs/10.1021/ac101560a}
}
@ARTICLE{Vanderwerf2009,
author = {Vanderwerf, Scott M. and Svahn, Johanna and Olson, Susan and Rathbun,
R. Keaney and Harrington, Christina and Yates, Jane and Keeble, Winifred
and Anderson, David C. and Anur, Praveen and Pereira, Noemi F. and
Pilonetto, Daniela V. and Pasquini, Ricardo and Bagby, Grover C.},
title = {TLR8-dependent TNF-{alpha} overexpression in Fanconi anemia group
C cells},
journal = {Blood},
year = {2009},
volume = {114},
pages = {5290--5298},
number = {26},
month = dec,
abstract = {Tumor necrosis factor alpha (TNF-{alpha}) production is abnormally
high in Fanconi anemia (FA) cells and contributes to the hematopoietic
defects seen in FA complementation group C-deficient (Fancc-/-) mice.
Applying gene expression microarray and proteomic methods to studies
on FANCC-deficient cells we found that genes encoding proteins directly
involved in ubiquitinylation are overrepresented in the signature
of FA bone marrow cells and that ubiquitinylation profiles of FA-C
and complemented cells were substantially different. Finding that
Toll-like receptor 8 (TLR8) was one of the proteins ubiquitinylated
only in mutant cells, we confirmed that TLR8 (or a TLR8-associated
protein) is ubiquitinylated in mutant FA-C cells and that TNF-{alpha}
production in mutant cells depended upon TLR8 and the canonical downstream
signaling intermediates interleukin 1 receptor-associated kinase
(IRAK) and I{kappa}B kinase-alpha/beta. FANCC-deficient THP-1 cells
and macrophages from Fancc-/- mice overexpressed TNF-{alpha} in response
to TLR8 agonists but not other TLR agonists. Ectopically expressed
FANCC point mutants were capable of fully complementing the mitomycin-C
hypersensitivity phenotype of FA-C cells but did not suppress TNF-{alpha}
overproduction. In conclusion, FANCC suppresses TNF-{alpha} production
in mononuclear phagocytes by suppressing TLR8 activity and this particular
function of FANCC is independent of its function in protecting the
genome from cross-linking agents.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/114/26/5290}
}
@ARTICLE{Vandeventer2011,
author = {Vandeventer, Peter E. and Weigel, Kris M. and Salazar, Jose and Erwin,
Barbara and Irvine, Bruce and Doebler, Robert and Nadim, Ali and
Cangelosi, Gerard A. and Niemz, Angelika},
title = {Mechanical Disruption of Lysis-Resistant Bacterial Cells by Use of
a Miniature, Low-Power, Disposable Device},
journal = {J. Clin. Microbiol.},
year = {2011},
volume = {49},
pages = {2533-2539},
number = {7},
abstract = {Molecular detection of microorganisms requires microbial cell disruption
to release nucleic acids. Sensitive detection of thick-walled microorganisms
such as Bacillus spores and Mycobacterium cells typically necessitates
mechanical disruption through bead beating or sonication, using benchtop
instruments that require line power. Miniaturized, low-power, battery-operated
devices are needed to facilitate mechanical pathogen disruption for
nucleic acid testing at the point of care and in field settings.
We assessed the lysis efficiency of a very small disposable bead
blender called OmniLyse relative to the industry standard benchtop
Biospec Mini-BeadBeater. The OmniLyse weighs approximately 3 g, at
a size of approximately 1.1 cm3 without the battery pack. Both instruments
were used to mechanically lyse Bacillus subtilis spores and Mycobacterium
bovis BCG cells. The relative lysis efficiency was assessed through
real-time PCR. Cycle threshold (CT) values obtained at all microbial
cell concentrations were similar between the two devices, indicating
that the lysis efficiencies of the OmniLyse and the BioSpec Mini-BeadBeater
were comparable. As an internal control, genomic DNA from a different
organism was spiked at a constant concentration into each sample
upstream of lysis. The CT values for PCR amplification of lysed samples
using primers specific to this internal control were comparable between
the two devices, indicating negligible PCR inhibition or other secondary
effects. Overall, the OmniLyse device was found to effectively lyse
tough-walled organisms in a very small, disposable, battery-operated
format, which is expected to facilitate sensitive point-of-care nucleic
acid testing.},
doi = {10.1128/JCM.02171-10},
eprint = {http://jcm.asm.org/cgi/reprint/49/7/2533.pdf},
url = {http://jcm.asm.org/cgi/content/abstract/49/7/2533}
}
@ARTICLE{Vandewalle2008,
author = {Vandewalle, Brigitte and Moerman, Ericka and Lefebvre, Bruno and
Defrance, Frédérique and Gmyr, Valéry and Lukowiak, Bruno and Kerr
Conte, Julie and Pattou, François},
title = {PPAR[gamma]-dependent and -independent effects of Rosiglitazone on
lipotoxic human pancreatic islets},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {366},
pages = {1096--1101},
number = {4},
month = feb,
abstract = {We explored the in vitro effects of Rosiglitazone (RZG), a PPAR[gamma]
agonist, on human pancreatic islet dysfunctions induced by chronic
free fatty acid exposure. We demonstrated that RZG beneficial effects
on insulin secretion and apoptosis did not imply PDX-1 or insulin
gene modulation. It rather involved, through a PPAR[gamma]-dependent
mechanism, a reduction of iNOS overexpressed in lipotoxic islets.
This reduction likely led to the restoration of ATP level and insulin
secretion as well as the decrease in apoptosis. More interestingly,
we also demonstrated that RZG beneficial effects involved PPAR[gamma]-independent
mechanisms. RZG treatment led to a limitation of oxidative stress
exemplified by an increase of GPx and SOD expression. It also increased
UCP2 expression that seemed to display antioxidant action in this
model. Thus, RZG did not appear to exert a direct action on insulin
expression but rather an indirect action on insulin secretion and
apoptosis, through PPAR[gamma]-dependent and -independent mechanisms,
via regulation of nitrogen and oxygen reactive species injury.},
issn = {0006-291X},
keywords = {Type 2 diabetes, Human pancreatic islets, Lipotoxicity, Rosiglitazone,
PPAR[gamma]-agonists, PPAR[gamma]-antagonists, PDX-1, UCP-2, iNOS},
url = {http://www.sciencedirect.com/science/article/B6WBK-4RFC9K7-8/2/e0fc57f6b99a2ae48a75553c1ff0dc0a}
}
@ARTICLE{Vandiedonck2011,
author = {Vandiedonck, Claire and Taylor, Martin S. and Lockstone, Helen E.
and Plant, Katharine and Taylor, Jennifer M. and Durrant, Caroline
and Broxholme, John and Fairfax, Benjamin P. and Knight, Julian C.},
title = {Pervasive haplotypic variation in the spliceo-transcriptome of the
human major histocompatibility complex},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {1042-1054},
number = {7},
abstract = {The human major histocompatibility complex (MHC) on chromosome 6p21
is a paradigm for genomics, showing remarkable polymorphism and striking
association with immune and non-immune diseases. The complex genomic
landscape of the MHC, notably strong linkage disequilibrium, has
made resolving causal variants very challenging. A promising approach
is to investigate gene expression levels considered as tractable
intermediate phenotypes in mapping complex diseases. However, how
transcription varies across the MHC, notably relative to specific
haplotypes, remains unknown. Here, using an original hybrid tiling
and splice junction microarray that includes alternate allele probes,
we draw the first high-resolution strand-specific transcription map
for three common MHC haplotypes (HLA-A1-B8-Cw7-DR3, HLA-A3-B7-Cw7-DR15,
and HLA-A26-B18-Cw5-DR3-DQ2) strongly associated with autoimmune
diseases including type 1 diabetes, systemic lupus erythematosus,
and multiple sclerosis. We find that haplotype-specific differences
in gene expression are common across the MHC, affecting 96 genes
(46.4%), most significantly the zing finger protein gene ZFP57. Differentially
expressed probes are correlated with polymorphisms between haplotypes,
consistent with cis effects that we directly demonstrate for ZFP57
in a cohort of healthy volunteers (P = 1.2 x 10-14). We establish
that alternative splicing is significantly more frequent in the MHC
than genome-wide (72.5% vs. 62.1% of genes, P [≤] 1 x 10-4) and
shows marked haplotypic differences. We also unmask novel and abundant
intergenic transcription involving 31% of transcribed blocks identified.
Our study reveals that the renowned MHC polymorphism also manifests
as transcript diversity, and our novel haplotype-based approach marks
a new step toward identification of regulatory variants involved
in the control of MHC-associated phenotypes and diseases.},
doi = {10.1101/gr.116681.110},
eprint = {http://genome.cshlp.org/cgi/reprint/21/7/1042.pdf},
url = {http://genome.cshlp.org/cgi/content/abstract/21/7/1042}
}
@ARTICLE{Vangipuram2008,
author = {Vangipuram, Sharada D. and Grever, William E. and Parker, Graham
C. and Lyman, William D.},
title = {Ethanol Increases Fetal Human Neurosphere Size and Alters Adhesion
Molecule Gene Expression},
journal = {Alcoholism: Clinical and Experimental Research},
year = {2008},
volume = {32},
pages = {339--347},
number = {2},
abstract = {Background:  Ethanol (ETOH) consumption by pregnant women can result
in Fetal Alcohol Spectrum Disorder (FASD). To date, the cellular
targets and mechanisms responsible for FASD are not fully characterized.
Our aim was to determine if ETOH can affect fetal human brain-derived
neural progenitor cells (NPC). Methods:  Neural progenitor cells
were isolated by positive selection from normal second trimester
fetal human brains (n = 4) and cultured, for up to 72 hours, in
mitogenic media containing 0, 1, 10, or 100Â mM ETOH. From 48 to
72Â hours in culture, neurospheres generated in these conditions
were filmed using time-lapse video microscopy. At the end of 72Â hours,
neurosphere diameter and roundness were measured using videographic
software. Mitotic phase analysis of cell-cycle activity and apoptotic
cell count were also performed at this time, by flow cytometry using
propidium iodide (PI) staining. Real-time PCR was used to estimate
expression of genes associated with cell adhesion pathways. Results: 
Neurosphere diameter correlated positively (r = 0.87) with increasing
ETOH concentrations. There was no significant difference in cell-cycle
activity and no significant increase in apoptosis with increasing
ETOH concentrations. Time-lapse video microscopy showed that ETOH
(100Â mM) reduced the time for neurosphere coalescence. Real-time
PCR analysis showed that ETOH significantly altered the expression
of genes involved in cell adhesion. There was an increase in the
expression of α and β Laminins 1, β Integrins 3 and 5, Secreted
phosphoprotein1 and Sarcoglycan ε. No change in the expression of
β Actin was observed while the expression of β Integrin 2 was significantly
suppressed. Conclusions:  ETOH had no effect on NPC apoptosis but,
resulted in more rapid coalescence and increased volume of neurospheres.
Additionally, the expression of genes associated with cell adhesion
was significantly altered. ETOH induced changes in NPC surface adhesion
interactions may underlie aspects of neurodevelopmental abnormalities
in FASD.},
issn = {1530-0277},
keywords = {Ethanol, Neurospheres, Neural Progenitor Cells, CD133, Cell Adhesion},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1530-0277.2007.00568.x}
}
@ARTICLE{Vangipuram2011,
author = {Vangipuram, Sharada D. and Lyman, William D.},
title = {Ethanol Affects Differentiation-Related Pathways and Suppresses Wnt
Signaling Protein Expression in Human Neural Stem Cells},
journal = {Alcoholism: Clinical and Experimental Research},
year = {2011},
pages = {no--no},
abstract = {Background:  Prenatal exposure of the fetus to ethanol (EtOH) can
be teratogenic. We previously showed that EtOH alters the cell fate
of human neural stem cells (NSC). As Wnt signaling plays an important
role in fetal brain development, we hypothesized that EtOH suppresses
Wnt signaling protein expression in differentiating NSC and thereby
contributes to fetal alcohol spectrum disorder.Methods:  NSC isolated
from fetal human brains were cultured in mitogenic media to induce
neurospheres, which were dissociated into single-cell suspensions
and used for all experiments. Equal numbers of NSC were cultured
on lysine/laminin-coated plates for 96Â hours in differentiating
media containing 0, 20, or 100Â mM EtOH. Total mRNA was isolated
from samples containing 0 or 100Â mM EtOH and changes in expression
of 263 genes associated with neurogenesis and NSC differentiation
were determined by Oligo GEArray technology. The biological impact
of gene changes was estimated using a systems biology approach with
pathway express software and KEGG database. Based on the pathways
identified, expression of Wnt proteins (Wnt3a and Wnt5a), Wnt-receptor
complex proteins (p-LRP6, LRP6, DVL2, and DVL3), Wnt antagonist Naked-2
(NKD-2), and downstream Wnt proteins (β-catenin, Tyr-p-GSK3β, Ser-p-GSK3β)
were analyzed by Western blot.Results:  Of the 263 genes examined,
the expressions of 22 genes in differentiating NSC were either upwardly
or downwardly affected by EtOH. These genes are associated with 5
pathways/cellular processes: axon guidance; hedgehog signaling; TGF-β
signaling; cell adhesion molecules; and Wnt signaling. When compared
to controls, EtOH, at both 20 and 100Â mM concentrations, suppressed
the expression of Wnt3a and Wnt5a, receptor complex proteins p-LRP6,
LRP6 and DVL2, and cytoplasmic proteins Ser-p-GSK3β and β-catenin.
Expression of NKD-2 and DVL3 remained unchanged and the expression
of active Tyr-p-GSK3β increased significantly.Conclusions:  EtOH
can significantly alter neural differentiation pathway-related gene
expression and suppress Wnt signaling proteins in differentiating
human NSC.},
doi = {10.1111/j.1530-0277.2011.01682.x},
issn = {1530-0277},
keywords = {Fetal Brain, Signaling Pathways, Ethanol},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1530-0277.2011.01682.x}
}
@ARTICLE{VanGuilder2011a,
author = {VanGuilder, Heather and Bixler, Georgina and Brucklacher, Robert
and Farley, Julie and Yan, Han and Warrington, Junie and Sonntag,
William and Freeman, Willard},
title = {Concurrent hippocampal induction of MHC II pathway components and
glial activation with advanced aging is not correlated with cognitive
impairment},
journal = {Journal of Neuroinflammation},
year = {2011},
volume = {8},
pages = {138},
number = {1},
abstract = {BACKGROUND:Age-related cognitive dysfunction, including impairment
of hippocampus-dependent spatial learning and memory, affects approximately
half of the aged population. Induction of a variety of neuroinflammatory
measures has been reported with brain aging but the relationship
between neuroinflammation and cognitive decline with non-neurodegenerative,
normative aging remains largely unexplored. This study sought to
comprehensively investigate expression of the MHC II immune response
pathway and glial activation in the hippocampus in the context of
both aging and age-related cognitive decline.METHODS:Three independent
cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats
were behaviorally characterized by Morris water maze testing. Expression
of MHC II pathway-associated genes identified by transcriptomic analysis
as upregulated with advanced aging was quantified by qPCR in synaptosomal
fractions derived from whole hippocampus and in hippocampal subregion
dissections (CA1, CA3, and DG). Activation of astrocytes and microglia
was assessed by GFAP and Iba1 protein expression, and by immunohistochemical
visualization of GFAP and both CD74 (Ox6) and Iba1.RESULTS:We report
a marked age-related induction of neuroinflammatory signaling transcripts
(i.e., MHC II components, toll-like receptors, complement, and downstream
signaling factors) throughout the hippocampus in all aged rats regardless
of cognitive status. Astrocyte and microglial activation was evident
in CA1, CA3 and DG of intact and impaired aged rat groups, in the
absence of differences in total numbers of GFAP+ astrocytes or Iba1+
microglia. Both mild and moderate microglial activation was significantly
increased in all three hippocampal subregions in aged cognitively
intact and cognitively impaired rats compared to adults. Neither
induction of MHCII pathway gene expression nor glial activation correlated
to cognitive performance.CONCLUSIONS:These data demonstrate a novel,
coordinated age-related induction of the MHC II immune response pathway
and glial activation in the hippocampus, indicating an allostatic
shift toward a para-inflammatory phenotype with advancing age. Our
findings demonstrate that age-related induction of these aspects
of hippocampal neuroinflammation, while a potential contributing
factor, is not sufficient by itself to elicit impairment of spatial
learning and memory in models of normative aging. Future efforts
are needed to understand how neuroinflammation may act synergistically
with cognitive-decline specific alterations to cause cognitive impairment.},
doi = {10.1186/1742-2094-8-138},
issn = {1742-2094},
pubmedid = {21989322},
url = {http://www.jneuroinflammation.com/content/8/1/138}
}
@ARTICLE{VanGuilder2008,
author = {VanGuilder, Heather D. and Brucklacher, Robert M. and Patel, Kruti
and Ellis, Rhona W. and Freeman, Willard M. and Barber, Alistair
J.},
title = {Diabetes downregulates presynaptic proteins and reduces basal synapsin
I phosphorylation in rat retina},
journal = {European Journal of Neuroscience},
year = {2008},
volume = {28},
pages = {1--11},
number = {1},
abstract = {Abstract Diabetic retinopathy can result in vision loss and involves
progressive neurovascular degeneration of the retina. This study
tested the hypothesis that diabetes decreases the retinal expression
of presynaptic proteins involved in synaptic function. The protein
and mRNA contents for synapsin I, synaptophysin, vesicle-associated
membrane protein 2, synaptosomal-associated protein of 25Â kDa and
postsynaptic density protein of 95Â kDa were measured by immunohistochemistry,
immunoblotting and real-time quantitative polymerase chain reaction
in whole retinas and retinal synaptosomes from streptozotocin-diabetic
and control Sprague–Dawley rats. There was less presynaptic protein
immunoreactivity after 1 and 3Â months of diabetes than in controls.
Discrete synaptophysin-immunoreactive puncta were significantly smaller
and fewer in sections from 1- and 3-month diabetic rat retinas than
in those from controls. The content of presynaptic proteins was significantly
less in whole retinas of 1- and 3-month diabetic rats, and in synaptosomes
from 1-month diabetic rats, than in controls. Whole retinas had significantly
less mRNA for these genes after 3Â months but not 1Â month of diabetes,
as compared to controls (with the exception of postsynaptic density
protein of 95Â kDa). In contrast, there was significantly less mRNA
for synaptic proteins in synaptosomes of 1-month diabetic rats than
in controls, suggesting a localized depletion at synapses. Protein
and mRNA for β-actin and neuron-specific enolase were unchanged
by diabetes. The ratio of phosphorylated to total synapsin I was
also reduced in whole retina and isolated synaptosomes from 1-month
diabetic rats, as compared to controls. These data suggest that diabetes
has a profound impact on presynaptic protein expression in the retina,
and may provide a mechanism for the well-established defects in vision
and the electrophysiological response of the retina in diabetes.},
issn = {1460-9568},
keywords = {diabetic retinopathy, neurodegeneration, SNARE, synaptophysin, synaptosome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2008.06322.x}
}
@ARTICLE{VanGuilder2011,
author = {VanGuilder, Heather D. and Farley, Julie A. and Yan, Han and Van
Kirk, Colleen A. and Mitschelen, Matthew and Sonntag, William E.
and Freeman, Willard M.},
title = {Hippocampal dysregulation of synaptic plasticity-associated proteins
with age-related cognitive decline},
journal = {Neurobiology of Disease},
year = {2011},
volume = {43},
pages = {201--212},
number = {1},
month = jul,
abstract = {Age-related cognitive decline occurs without frank neurodegeneration
and is the most common cause of memory impairment in aging individuals.
With increasing longevity, cognitive deficits, especially in hippocampus-dependent
memory processes, are increasing in prevalence. Nevertheless, the
neurobiological basis of age-related cognitive decline remains unknown.
While concerted efforts have led to the identification of neurobiological
changes with aging, few age-related alterations have been definitively
correlated to behavioral measures of cognitive decline. In this work,
adult (12 months) and aged (28 months) rats were categorized by Morris
water maze performance as Adult cognitively Intact, Aged cognitively
Intact or Aged cognitively Impaired, and protein expression was examined
in hippocampal synaptosome preparations. Previously described differences
in synaptic expression of neurotransmission-associated proteins (Dnm1,
Hpca, Stx1, Syn1, Syn2, Syp, SNAP25, VAMP2 and 14-3-3 eta, gamma,
and zeta) were confirmed between Adult and Aged rats, with no further
dysregulation associated with cognitive impairment. Proteins related
to synaptic structural stability (MAP2, drebrin, Nogo-A) and activity-dependent
signaling (PSD-95, 14-3-3[theta], CaMKII[alpha]) were up- and down-regulated,
respectively, with cognitive impairment but were not altered with
increasing age. Localization of MAP2, PSD-95, and CaMKII[alpha] demonstrated
protein expression alterations throughout the hippocampus. The altered
expression of activity- and structural stability-associated proteins
suggests that impaired synaptic plasticity is a distinct phenomenon
that occurs with age-related cognitive decline, and demonstrates
that cognitive decline is not simply an exacerbation of the aging
phenotype.},
booktitle = {Autophagy and protein degradation in neurological diseases},
issn = {0969-9961},
keywords = {Nogo, CamkII, Aging, Hippocampus, Synapse, Learning and memory},
url = {http://www.sciencedirect.com/science/article/pii/S0969996111000945}
}
@ARTICLE{Vanhoudt2011,
author = {Nathalie Vanhoudt and Ann Cuypers and Nele Horemans and Tony Remans
and Kelly Opdenakker and Karen Smeets and Daniel Martinez Bello and
Michel Havaux and Jean Wannijn and May Van Hees and Jaco Vangronsveld
and Hildegarde Vandenhove},
title = {Unraveling uranium induced oxidative stress related responses in
Arabidopsis thaliana seedlings. Part II: responses in the leaves
and general conclusions},
journal = {Journal of Environmental Radioactivity},
year = {2011},
volume = {102},
pages = {638 - 645},
number = {6},
abstract = {The cellular redox balance seems an important modulator under heavy
metal stress. While for other heavy metals these processes are well
studied, oxidative stress related responses are also known to be
triggered under uranium stress but information remains limited. This
study aimed to further unravel the mechanisms by which plants respond
to uranium stress. Seventeen-day-old Arabidopsis thaliana seedlings,
grown on a modified Hoagland solution under controlled conditions,
were exposed to 0, 0.1, 1, 10 and 100 μM uranium for 1, 3 and 7
days. While in Part I of this study oxidative stress related responses
in the roots were discussed, this second Part II discusses oxidative
stress related responses in the leaves and general conclusions drawn
from the results of the roots and the leaves will be presented. As
several responses were already visible following 1 day exposure,
when uranium concentrations in the leaves were negligible, a root-to-shoot
signaling system was suggested in which plastids could be important
sensing sites. While lipid peroxidation, based on the amount of thiobarbituric
acid reactive compounds, was observed after exposure to 100 μM
uranium, affecting membrane structure and function, a transient concentration
dependent response pattern was visible for lipoxygenase initiated
lipid peroxidation. This transient character of uranium stress responses
in leaves was emphasized by results of lipoxygenase (LOX2) and antioxidative
enzyme transcript levels, enzyme capacities and glutathione concentrations
both in time as with concentration. The ascorbate redox balance seemed
an important modulator of uranium stress responses in the leaves
as in addition to the previous transient responses, the total ascorbate
concentration and ascorbate/dehydroascorbate redox balance increased
in a concentration and time dependent manner. This could represent
either a slow transient response or a stable increase with regard
to plant acclimation to uranium stress.},
doi = {10.1016/j.jenvrad.2011.03.013},
issn = {0265-931X},
keywords = {Arabidopsis thaliana},
url = {http://www.sciencedirect.com/science/article/pii/S0265931X11000592}
}
@ARTICLE{Vanhoudt2011a,
author = {Vanhoudt, Nathalie and Vandenhove, Hildegarde and Horemans, Nele
and Remans, Tony and Opdenakker, Kelly and Smeets, Karen and Bello,
Daniel Martinez and Wannijn, Jean and Van Hees, May and Vangronsveld,
Jaco and Cuypers, Ann},
title = {Unraveling uranium induced oxidative stress related responses in
Arabidopsis thaliana seedlings. Part I: responses in the roots},
journal = {Journal of Environmental Radioactivity},
year = {2011},
volume = {102},
pages = {630--637},
number = {6},
month = jun,
abstract = {When aiming to evaluate the environmental impact of uranium contamination,
it is important to unravel the mechanisms by which plants respond
to uranium stress. As oxidative stress seems an important modulator
under other heavy metal stress, this study aimed to investigate oxidative
stress related responses in Arabidopsis thaliana exposed to uranium
concentrations ranging from 0.1 to 100 [mu]M for 1, 3 and 7 days.
Besides analyzing relevant reactive oxygen species-producing and
-scavenging enzymes at protein and transcriptional level, the importance
of the ascorbate-glutathione cycle under uranium stress was investigated.
These results are reported separately for roots and leaves in two
papers: Part I dealing with responses in the roots and Part II unraveling
responses in the leaves and presenting general conclusions. Results
of Part I indicate that oxidative stress related responses in the
roots were only triggered following exposure to the highest uranium
concentration of 100 [mu]M. A fast oxidative burst was suggested
based on the observed enhancement of lipoxygenase (LOX1) and respiratory
burst oxydase homolog (RBOHD) transcript levels already after 1 day.
The first line of defense was attributed to superoxide dismutase
(SOD), also triggered from the first day. The enhanced SOD-capacity
observed at protein level corresponded with an enhanced expression
of iron SOD (FSD1) located in the plastids. For the detoxification
of H2O2, an early increase in catalase (CAT1) transcript levels was
observed while peroxidase capacities were enhanced at the later stage
of 3 days. Although the ascorbate peroxidase capacity and gene expression
(APX1) increased, the ascorbate/dehydroascorbate redox balance was
completely disrupted and shifted toward the oxidized form. This disrupted
balance could not be inverted by the glutathione part of the cycle
although the glutathione redox balance could be maintained.},
issn = {0265-931X},
keywords = {Antioxidative defense system, Arabidopsis thaliana, Gene expression,
Oxidative stress, Uranium toxicity},
url = {http://www.sciencedirect.com/science/article/pii/S0265931X11000610}
}
@ARTICLE{Vanhoudt2010a,
author = {Vanhoudt, Nathalie and Vandenhove, Hildegarde and Horemans, Nele
and Wannijn, Jean and Bujanic, Andelko and Vangronsveld, Jaco and
Cuypers, Ann},
title = {Study of oxidative stress related responses induced in Arabidopsis
thaliana following mixed exposure to uranium and cadmium},
journal = {Plant Physiology and Biochemistry},
year = {2010},
volume = {48},
pages = {879--886},
number = {10-11},
month = oct,
abstract = {In this study, toxicity effects in plants of uranium in a binary pollution
condition were investigated by studying biological responses and
unraveling oxidative stress related mechanisms in Arabidopsis thaliana
seedlings, grown on hydroponics and exposed for 3 days to 10 [mu]M
uranium in combination with 5 [mu]M cadmium. While uranium mostly
accumulated in the roots with very low root-to-shoot transport, cadmium
was taken up less by the roots but showed higher translocation to
the shoots. Under mixed exposure, cadmium influenced uranium uptake
highly but not the other way round resulting in a doubled uranium
concentration in the roots. Under our mixed exposure conditions,
it is clear that micronutrient concentrations in the roots are strongly
influenced by addition of cadmium as a second stressor, while leaf
macronutrient concentrations are mostly influenced by uranium. Oxidative
stress related responses are highly affected by cadmium while uranium
influence is more limited. Hereby, an important role was attributed
to the ascorbate redox balance together with glutathione as both
metabolites, but more explicitly for ascorbate, increased their reduced
form, indicating an important defense and regulatory function. While
for roots, based on an increase in FSD1 gene expression, oxidative
stress was suggested to be superoxide induced, in leaves on the other
hand, hydrogen peroxide related genes were mostly altered.},
issn = {0981-9428},
keywords = {Arabidopsis thaliana, Binary mixture, Cadmium, Gene expression, Oxidative
stress, Uranium},
url = {http://www.sciencedirect.com/science/article/B6VRD-50THX88-3/2/52eec7899457be7706aeb8047ab3cb7e}
}
@ARTICLE{Vanhoudt2010,
author = {Vanhoudt, Nathalie and Vandenhove, Hildegarde and Horemans, Nele
and Wannijn, Jean and Van Hees, May and Vangronsveld, Jaco and Cuypers,
Ann},
title = {The combined effect of uranium and gamma radiation on biological
responses and oxidative stress induced in Arabidopsis thaliana},
journal = {Journal of Environmental Radioactivity},
year = {2010},
volume = {101},
pages = {923--930},
number = {11},
month = nov,
abstract = {Uranium never occurs as a single pollutant in the environment, but
always in combination with other stressors such as ionizing radiation.
As effects induced by multiple contaminants can differ markedly from
the effects induced by the individual stressors, this multiple pollution
context should not be neglected. In this study, effects on growth,
nutrient uptake and oxidative stress induced by the single stressors
uranium and gamma radiation are compared with the effects induced
by the combination of both stressors. By doing this, we aim to better
understand the effects induced by the combined stressors but also
to get more insight in stressor-specific response mechanisms. Eighteen-day-old
Arabidopsis thaliana seedlings were exposed for 3 days to 10 [mu]M
uranium and 3.5 Gy gamma radiation. Gamma radiation interfered with
uranium uptake, resulting in decreased uranium concentrations in
the roots, but with higher transport to the leaves. This resulted
in a better root growth but increased leaf lipid peroxidation. For
the other endpoints studied, effects under combined exposure were
mostly determined by uranium presence and only limited influenced
by gamma presence. Furthermore, an important role is suggested for
CAT1/2/3 gene expression under uranium and mixed stressor conditions
in the leaves.},
issn = {0265-931X},
keywords = {Arabidopsis thaliana, Enzyme capacity, Gamma radiation, Gene expression,
Oxidative stress, Uranium contamination},
url = {http://www.sciencedirect.com/science/article/B6VB2-50J3D90-1/2/ce4d513cb60892ff0881b0af9d022b7f}
}
@ARTICLE{Vani2007,
author = {Vani, Susheel and McDonald, Sarah E. and Williams, Alistair R.W.
and Mason, J. Ian and Thong, K. Joo and Critchley, Hilary O.D.},
title = {Mid-luteal endometrial intracrinology following controlled ovarian
hyperstimulation involving use of a gonadotrophin releasing hormone
antagonist},
journal = {Hum. Reprod.},
year = {2007},
volume = {22},
pages = {2981--2991},
number = {11},
month = nov,
abstract = {BACKGROUNDThere are concerns of reduced pregnancy rates with the use
of gonadotrophin-releasing hormone antagonists (GnRH antagonists)
in IVF/ICSI cycles. Sex steroids and their metabolizing enzymes in
the endometrium may play a vital role in embryo implantation. This
study has evaluated the levels and localization of sex-steroid receptors
and metabolizing enzymes, 3{beta}-hydroxysteroid dehydrogenases (3{beta}HSD)
and selected 17{beta}-HSD (17{beta}HSD), in mid-luteal endometrium
of women treated with GnRH antagonist (Cetrorelix) and recombinant
FSH (rFSH; Gonal-F) with luteal phase progesterone supplementation.
METHODSMid-luteal phase endometrial biopsies were obtained from oocyte
donors undergoing ovarian stimulation and from control women with
regular periods. Immunohistochemistry and real-time quantitative-polymerase
chain reaction (QRT-PCR) were used to compare protein and mRNA expression
of progesterone receptor (PR), estrogen receptor {alpha} (ER{alpha}),
estrogen receptor {beta} (ER{beta}), androgen receptor (AR), 3{beta}HSD1,
3{beta}HSD2, 17{beta}HSD2 and 17{beta}HSD5. RESULTSCetrorelix-rFSH
treatment caused a mid-luteal suppression of PR protein expression
in the endometrial stroma, surface epithelium and glands, although
expression in the glands of control samples was variable. In contrast,
the treatment caused an increase in PR staining in perivascular cells.
No other significant differences in protein expression were observed
between the two groups. mRNA levels of AR, ER{alpha}, 3{beta}HSD1
and 17{beta}HSD2 were significantly reduced in the treatment group.
PR mRNA levels were also reduced by GnRH antagonist-rFSH treatment,
but the difference was not significant. CONCLUSIONSChanges in the
expression of sex-steroid receptors and metabolizing enzymes may
lead to alterations in the activity and intracellular availability
of estrogens, progestogens and androgens in endometrium of women
treated with Cetrorelix and rFSH. Their impact on embryo implantation
merits further evaluation.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/22/11/2981}
}
@ARTICLE{Vankoningsloo2008,
author = {Vankoningsloo, Sebastien and De Longueville, Francoise and Evrard,
Stephanie and Rahier, Pierre and Houbion, Andree and Fattaccioli,
Antoine and Gastellier, Melanie and Remacle, Jose and Raes, Martine
and Renard, Patricia and Arnould, Thierry},
title = {Gene expression silencing with ´specific´ small interfering RNA goes
beyond specificity - a study of key parameters to take into account
in the onset of small interfering RNA off-target effects},
journal = {FEBS Journal},
year = {2008},
volume = {275},
pages = {2738--2753},
number = {11},
abstract = {RNA-mediated gene silencing (RNA interference) is a powerful way to
knock down gene expression and has revolutionized the fields of cellular
and molecular biology. Indeed, the transfection of cultured cells
with small interfering RNAs (siRNAs) is currently considered to be
the best and easiest approach to loss-of-function experiments. However,
several recent studies underscore the off-target and potential cytotoxic
effects of siRNAs, which can lead to the silencing of unintended
mRNAs. In this study, we used a low-density microarray to assess
gene expression modifications in response to five different siRNAs
in various cell types and transfection conditions. We found major
differences in off-target signature according to: (a) siRNA sequence;
(b) cell type; (c) duration of transfection; and (d) post-transfection
time before analysis. These results contribute to a better understanding
of important parameters that could impact on siRNA side effects in
knockdown experiments.},
issn = {1742-4658},
keywords = {cell type, gene expression, off-target effects, silencing, siRNA},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1742-4658.2008.06415.x}
}
@ARTICLE{Vankoningsloo2006,
author = {Vankoningsloo, Sebastien and De Pauw, Aurelia and Houbion, Andree
and Tejerina, Silvia and Demazy, Catherine and de Longueville, Francoise
and Bertholet, Vincent and Renard, Patricia and Remacle, Jose and
Holvoet, Paul and Raes, Martine and Arnould, Thierry},
title = {CREB activation induced by mitochondrial dysfunction triggers triglyceride
accumulation in 3T3-L1 preadipocytes},
journal = {J. Cell Sci.},
year = {2006},
volume = {119},
pages = {1266--1282},
number = {7},
month = apr,
abstract = {Several mitochondrial pathologies are characterized by lipid redistribution
and microvesicular cell phenotypes resulting from triglyceride accumulation
in lipid-metabolizing tissues. However, the molecular mechanisms
underlying abnormal fat distribution induced by mitochondrial dysfunction
remain poorly understood. In this study, we show that inhibition
of respiratory complex III by antimycin A as well as inhibition of
mitochondrial protein synthesis trigger the accumulation of triglyceride
vesicles in 3T3-L1 fibroblasts. We also show that treatment with
antimycin A triggers CREB activation in these cells. To better delineate
how mitochondrial dysfunction induces triglyceride accumulation in
preadipocytes, we developed a low-density DNA microarray containing
89 probes, which allows gene expression analysis for major effectors
and/or markers of adipogenesis. We thus determined gene expression
profiles in 3T3-L1 cells incubated with antimycin A and compared
the patterns obtained with differentially expressed genes during
the course of in vitro adipogenesis induced by a standard pro-adipogenic
cocktail. After an 8-day treatment, a set of 39 genes was found to
be differentially expressed in cells treated with antimycin A, among
them CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), C/EBP
homologous protein-10 (CHOP-10), mitochondrial glycerol-3-phosphate
dehydrogenase (GPDmit), and stearoyl-CoA desaturase 1 (SCD1). We
also demonstrate that overexpression of two dominant negative mutants
of the cAMP-response element-binding protein CREB (K-CREB and M1-CREB)
and siRNA transfection, which disrupt the factor activity and expression,
respectively, inhibit antimycin-A-induced triglyceride accumulation.
Furthermore, CREB knockdown with siRNA also downregulates the expression
of several genes that contain cAMP-response element (CRE) sites in
their promoter, among them one that is potentially involved in synthesis
of triglycerides such as SCD1. These results highlight a new role
for CREB in the control of triglyceride metabolism during the adaptative
response of preadipocytes to mitochondrial dysfunction.},
url = {http://jcs.biologists.org/cgi/content/abstract/119/7/1266}
}
@ARTICLE{Vannerum2011,
author = {Vannerum, Katrijn and Huysman, Marie and De Rycke, Riet and Vuylsteke,
Marnik and Leliaert, Frederik and Pollier, Jacob and Lutz-Meindl,
Ursula and Gillard, Jeroen and De Veylder, Lieven and Goossens, Alain
and Inze, Dirk and Vyverman, Wim},
title = {Transcriptional analysis of cell growth and morphogenesis in the
unicellular green alga Micrasterias (Streptophyta), with emphasis
on the role of expansin},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {128},
number = {1},
abstract = {BACKGROUND:Streptophyte green algae share several characteristics
of cell growth and cell wall formation with their relatives, the
embryophytic land plants. The multilobed cell wall of Micrasterias
denticulata that rebuilds symmetrically after cell division and consists
of pectin and cellulose, makes this unicellular streptophyte alga
an interesting model system to study the molecular controls on cell
shape and cell wall formation in green plants.RESULTS:Genome-wide
transcript expression profiling of synchronously growing cells identified
107 genes of which the expression correlated with the growth phase.
Four transcripts showed high similarity to expansins that had not
been examined previously in green algae. Phylogenetic analysis suggests
that these genes are most closely related to the plant EXPANSIN A
family, although their domain organization is very divergent. A GFP-tagged
version of the expansin-resembling protein MdEXP2 localized to the
cell wall and in Golgi-derived vesicles. Overexpression phenotypes
ranged from lobe elongation to loss of growth polarity and planarity.
These results indicate that MdEXP2 can alter the cell wall structure
and, thus, might have a function related to that of land plant expansins
during cell morphogenesis.CONCLUSIONS:Our study demonstrates the
potential of M. denticulata as a unicellular model system, in which
cell growth mechanisms have been discovered similar to those in land
plants. Additionally, evidence is provided that the evolutionary
origins of many cell wall components and regulatory genes in embryophytes
precede the colonization of land.},
doi = {10.1186/1471-2229-11-128},
issn = {1471-2229},
pubmedid = {21943227},
url = {http://www.biomedcentral.com/1471-2229/11/128}
}
@ARTICLE{VanyaEwart2008,
author = {Vanya Ewart, K. and Williams, Jason and Richards, Robert C. and Gallant,
Jeffrey W. and Melville, Krista and Douglas, Susan E.},
title = {The early response of Atlantic salmon (Salmo salar) macrophages exposed
in vitro to Aeromonas salmonicida cultured in broth and in fish},
journal = {Developmental \& Comparative Immunology},
year = {2008},
volume = {32},
pages = {380--390},
number = {4},
abstract = {Aeromonas salmonicida is a fish pathogen that causes furunculosis.
Virulent strains of this bacterium are able to infect salmonid macrophages
and survive within them, although mechanisms favouring intracellular
survival are not completely understood. It is known that A. salmonicida
cultured in vivo in the peritoneal cavity of the host undergoes changes
in gene expression and surface architecture compared with cultures
grown in vitro in broth. Therefore, in this study, the early macrophage
responses to A. salmonicida grown in vivo and in vitro were compared.
Macrophage-enriched cell preparations from head kidney of Atlantic
salmon (Salmo salar) were infected in vitro in 96-well microtitre
dishes and changes in gene expression during the infection process
were monitored using a custom Atlantic salmon cDNA microarray. A.
salmonicida cultures grown in tryptic soy broth and in peritoneal
implants were used to infect the macrophages. The macrophages were
harvested at 0.5, 1.0 and 2.0 h after addition of the bacteria to
the medium. Significant changes in gene expression were evident by
microarray analysis at 2.0 h post-infection in macrophages infected
with broth-grown and implant-grown bacteria; however, qPCR analysis
revealed earlier up-regulation of JunB and TNF-[alpha] in macrophages
exposed to the implant-grown bacteria. Up-regulation of those genes
and others is consistent with the effects of extracellular products
of aeromonad bacteria on macrophages and also suggests initiation
of the innate immune response.},
issn = {0145-305X},
keywords = {Inflammation, Acute phase response, Fish, Microarray, qPCR},
url = {http://www.sciencedirect.com/science/article/B6T5X-4PG2JJG-1/2/43a95fef65a29849ed500248d2edc28c}
}
@ARTICLE{Varambally2005,
author = {Varambally, Sooryanarayana and Yu, Jianjun and Laxman, Bharathi and
Rhodes, Daniel R. and Mehra, Rohit and Tomlins, Scott A. and Shah,
Rajal B. and Chandran, Uma and Monzon, Federico A. and Becich, Michael
J. and Wei, John T. and Pienta, Kenneth J. and Ghosh, Debashis and
Rubin, Mark A. and Chinnaiyan, Arul M.},
title = {Integrative genomic and proteomic analysis of prostate cancer reveals
signatures of metastatic progression},
journal = {Cancer Cell},
year = {2005},
volume = {8},
pages = {393--406},
number = {5},
month = nov,
abstract = {Summary Molecular profiling of cancer at the transcript level has
become routine. Large-scale analysis of proteomic alterations during
cancer progression has been a more daunting task. Here, we employed
high-throughput immunoblotting in order to interrogate tissue extracts
derived from prostate cancer. We identified 64 proteins that were
altered in prostate cancer relative to benign prostate and 156 additional
proteins that were altered in metastatic disease. An integrative
analysis of this compendium of proteomic alterations and transcriptomic
data was performed, revealing only 48%-64% concordance between protein
and transcript levels. Importantly, differential proteomic alterations
between metastatic and clinically localized prostate cancer that
mapped concordantly to gene transcripts served as predictors of clinical
outcome in prostate cancer as well as other solid tumors.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-4HJRXFF-7/2/18e567a7dcaa45c2b2226a178ef4754e}
}
@ARTICLE{Varela2010,
author = {Varela, Elisa and Schlecht, Ulrich and Moina, Anca and Fackenthal,
James D. and Washburn, Brian K. and Niederhauser-Wiederkehr, Christa
and Tsai-Pflugfelder, Monika and Primig, Michael and Gasser, Susan
M. and Esposito, Rochelle E.},
title = {Mitotic Expression of Spo13 Alters M-Phase Progression and Nucleolar
Localization of Cdc14 in Budding Yeast},
journal = {Genetics},
year = {2010},
volume = {185},
pages = {841--854},
number = {3},
month = jul,
abstract = {Spo13 is a key meiosis-specific regulator required for centromere
cohesion and coorientation, and for progression through two nuclear
divisions. We previously reported that it causes a G2/M arrest and
may delay the transition from late anaphase to G1, when overexpressed
in mitosis. Yet its mechanism of action has remained elusive. Here
we show that Spo13, which is phosphorylated and stabilized at G2/M
in a Cdk/Clb-dependent manner, acts at two stages during mitotic
cell division. Spo13 provokes a G2/M arrest that is reversible and
largely independent of the Mad2 spindle checkpoint. Since mRNAs whose
induction requires Cdc14 activation are reduced, we propose that
its anaphase delay results from inhibition of Cdc14 function. Indeed,
the Spo13-induced anaphase delay correlates with Cdc14 phosphatase
retention in the nucleolus and with cyclin B accumulation, which
both impede anaphase exit. At the onset of arrest, Spo13 is primarily
associated with the nucleolus, where Cdc14 accumulates. Significantly,
overexpression of separase (Esp1), which promotes G2/M and anaphase
progression, suppresses Spo13 effects in mitosis, arguing that Spo13
acts upstream or parallel to Esp1. Given that Spo13 overexpression
reduces Pds1 and cyclin B degradation, our findings are consistent
with a role for Spo13 in regulating APC, which controls both G2/M
and anaphase. Similar effects of Spo13 during meiotic MI may prevent
cell cycle exit and initiation of DNA replication prior to MII, thereby
ensuring two successive chromosome segregation events without an
intervening S phase.},
url = {http://www.genetics.org/cgi/content/abstract/185/3/841}
}
@ARTICLE{Varela2007,
author = {Varela, M. A. And Gonzalez-Tizon, A. And Francisco-candeira, M. And
Martinez-lage, A.},
title = {Isolation and characterization of polymorphic microsatellite loci
in the razor clam Ensis siliqua},
journal = {Molecular Ecology Notes},
year = {2007},
volume = {7},
pages = {221--222},
number = {2},
abstract = {Abstract Five polymorphic microsatellite loci in the razor clam Ensis
siliqua are described. A collection consisting of 34 individuals
from Finisterre, Spain, was analysed. Loci were isolated from the
sequences of intersimple sequence repeat (ISSR) markers. Detailed
analysis of 42 ISSR markers led to the design of 16 primer pairs.
Five of these yielded consistent and polymorphic products. The number
of alleles ranged from five to 23 per locus with the observed heterozygosity
ranging from 0.46 to 0.94. Linkage equilibrium was observed in all
loci and three of them showed significant deviations from Hardy–Weinberg
equilibrium.},
issn = {1471-8286},
keywords = {Ensis siliqua, ISSR, microsatellites, razor clam},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-8286.2006.01423.x}
}
@ARTICLE{Varesio2010,
author = {Varesio, Luigi and Battaglia, Florinda and Raggi, Federica and Ledda,
Bernadetta and Bosco, Maria Carla},
title = {Macrophage-inflammatory protein-3[alpha]/CCL-20 is transcriptionally
induced by the iron chelator desferrioxamine in human mononuclear
phagocytes through nuclear factor (NF)-[kappa]B},
journal = {Molecular Immunology},
year = {2010},
volume = {47},
pages = {685--693},
number = {4},
month = jan,
abstract = {Alterations in iron availability can trigger pro-inflammatory signals
in various cell types. We demonstrate that desferrioxamine (DFX),
an iron chelator used in clinics for the treatment of iron overload,
neoplasias, and Alzheimer disease, stimulates the expression and
secretion of CCL20, a chemoattractant for immature dendritic cells,
activated/memory T lymphocytes, and naive B cells, in primary human
monocytes and monocyte-derived macrophages. Iron chelation was part
of the mechanism by which DFX induced CCL20, because addition of
iron sulfate counteracted its stimulatory effects. Functional studies
of the CCL20 promoter, using a series of 5'-deleted and mutated reporter
constructs, demonstrated that CCL20 mRNA induction was dependent
on gene transcription activation and mediated by the NF-[kappa]B
pathway. The NF-[kappa]B element located at position -92/-82 of the
CCL20 promoter was required for gene transactivation by DFX because:
(i) transcription was abrogated by a 3 bp mutation of the NF-[kappa]B-binding
motif; (ii) treatment with DFX increased specific NF-[kappa]B binding
to this sequence. Nuclear translocation of both NF-[kappa]Bp65 and
NF-[kappa]Bp50 family members was increased in response to DFX and
associated with I-[kappa]B[alpha] degradation, suggesting a role
for these subunits in CCL20 promoter transactivation. In conclusion,
this study provides the first evidence that iron chelation can transcriptionally
induce CCL20 in mononuclear phagocytes and identify the NF-[kappa]B
binding site as a regulatory sequence of the CCL20 promoter that
is activated by iron deprivation. These results add new insights
into our understanding of the mechanisms by which iron perturbations
affect mononuclear phagocyte immune functions and regulate inflammatory
responses.},
issn = {0161-5890},
keywords = {Monocytes/macrophages, Iron chelation, Chemokines, Gene regulation,
Inflammation},
url = {http://www.sciencedirect.com/science/article/B6T9R-4XSK7PN-2/2/b7592e5bf6eb9f1fcb7bbc496e116047}
}
@ARTICLE{Vargas2008,
author = {Vargas, Marcelo R. and Johnson, Delinda A. and Sirkis, Daniel W.
and Messing, Albee and Johnson, Jeffrey A.},
title = {Nrf2 Activation in Astrocytes Protects against Neurodegeneration
in Mouse Models of Familial Amyotrophic Lateral Sclerosis},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {13574--13581},
number = {50},
month = dec,
abstract = {Activation of the transcription factor Nrf2 in astrocytes coordinates
the upregulation of antioxidant defenses and confers protection to
neighboring neurons. Dominant mutations in Cu/Zn-superoxide dismutase
(SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS),
a fatal disorder characterized by the progressive loss of motor neurons.
Non-neuronal cells, including astrocytes, shape motor neuron survival
in ALS and are a potential target to prevent motor neuron degeneration.
The protective effect of Nrf2 activation in astrocytes has never
been examined in a chronic model of neurodegeneration. We generated
transgenic mice over-expressing Nrf2 selectively in astrocytes using
the glial fibrillary acidic protein (GFAP) promoter. The toxicity
of astrocytes expressing ALS-linked mutant hSOD1 to cocultured motor
neurons was reversed by Nrf2 over-expression. Motor neuron protection
depended on increased glutathione secretion from astrocytes. This
protective effect was also observed by crossing the GFAP-Nrf2 mice
with two ALS-mouse models. Over-expression of Nrf2 in astrocytes
significantly delayed onset and extended survival. These findings
demonstrate that Nrf2 activation in astrocytes is a viable therapeutic
target to prevent chronic neurodegeneration.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/50/13574}
}
@ARTICLE{Vargas2008a,
author = {Vargas, Marcelo R. and Pehar, Mariana and DÃaz-Amarilla, Pablo J.
and Beckman, Joseph S. and Barbeito, Luis},
title = {Transcriptional profile of primary astrocytes expressing ALS-linked
mutant SOD1},
journal = {J. Neurosci. Res.},
year = {2008},
volume = {86},
pages = {3515--3525},
number = {16},
abstract = {Abstract 10.1002/jnr.21797.abs Amyotrophic lateral sclerosis (ALS)
is caused by the progressive degeneration of motor neurons. Mutations
in the Cu/Zn superoxide dismutase (SOD1) are found in approximately
20% of patients with familial ALS. Mutant SOD1 causes motor neuron
death through an acquired toxic property. Although the molecular
mechanism underlying this toxic gain-of-function remains unknown,
evidence support the role of mutant SOD1 expression in nonneuronal
cells in shaping motor neuron degeneration. We have previously found
that in contrast to nontransgenic cells, SOD1G93A-expressing astrocytes
induced apoptosis of cocultured motor neurons. This prompted us to
investigate whether the effect on motor neuron survival was related
to a change in the gene expression profile. Through high-density
oligonucleotide microarrays, we found changes in the expression of
genes involved in transcription, signaling, cell proliferation, extracellular
matrix synthesis, response to stress, and steroid and lipid metabolism.
The most up-regulated gene was decorin (Dcn), a small multifunctional
extracellular proteoglycan. Down-regulated genes included the insulin-like
growth factor-1 receptor (Igf-1r) and the RNA binding protein ROD1.
Rod1 was also found down-regulated in purified motor neurons expressing
SOD1G93A. Changes in the expression of Dcn, Igf-1r, and Rod1 were
found in the spinal cord of asymptomatic animals, suggesting these
changes occur before overt neuronal degeneration and potentially
influence astrocyte–motor neuron interaction in the course of the
disease. The astrocyte-specific gene expression profile might contribute
to the identification of possible candidates for cell type-specific
therapies in ALS. © 2008 Wiley-Liss, Inc.},
issn = {1097-4547},
keywords = {motor neurons, decorin, IGF-1R, ROD1, microarray},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.21797}
}
@ARTICLE{Vargova2011,
author = {Vargova, Karin and Curik, Nikola and Burda, Pavel and Basova, Petra
and Kulvait, Vojtech and Pospisil, Vit and Savvulidi, Filipp and
Kokavec, Juraj and Necas, Emanuel and Berkova, Adela and Obrtlikova,
Petra and Karban, Josef and Mraz, Marek and Pospisilova, Sarka and
Mayer, Jiri and Trneny, Marek and Zavadil, Jiri and Stopka, Tomas},
title = {MYB transcriptionally regulates the miR-155 host gene in chronic
lymphocytic leukemia},
journal = {Blood},
year = {2011},
volume = {117},
pages = {3816--3825},
number = {14},
month = apr,
abstract = {Elevated levels of microRNA miR-155 represent a candidate pathogenic
factor in chronic B-lymphocytic leukemia (B-CLL). In this study,
we present evidence that MYB (v-myb myeloblastosis viral oncogene
homolog) is overexpressed in a subset of B-CLL patients. MYB physically
associates with the promoter of miR-155 host gene (MIR155HG, also
known as BIC, B-cell integration cluster) and stimulates its transcription.
This coincides with the hypermethylated histone H3K4 residue and
spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide
evidence of oncogenic activities of MYB in B-CLL that include its
stimulatory role in MIR155HG transcription.},
comment = {10.1182/blood-2010-05-285064},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/14/3816}
}
@ARTICLE{Varma2008,
author = {Varma, Vijayalakshmi and Yao-Borengasser, Aiwei and Bodles, Angela
M. and Rasouli, Neda and Phanavanh, Bounleut and Nolen, Greg T. and
Kern, Emily M. and Nagarajan, Radhakrishnan and Spencer, Horace J.,
III and Lee, Mi-Jeong and Fried, Susan K. and McGehee, Robert E.,
Jr. and Peterson, Charlotte A. and Kern, Philip A.},
title = {Thrombospondin-1 Is an Adipokine Associated With Obesity, Adipose
Inflammation, and Insulin Resistance},
journal = {Diabetes},
year = {2008},
volume = {57},
pages = {432--439},
number = {2},
month = feb,
abstract = {OBJECTIVE--We examined the relationship between the expression of
thrombospondin (TSP)1, an antiangiogenic factor and regulator of
transforming growth factor-{beta} activity, obesity, adipose inflammation,
and insulin resistance. RESEARCH DESIGN AND METHODS--TSP1 gene expression
was quantified in subcutaneous adipose tissue (SAT) of 86 nondiabetic
subjects covering a wide range of BMI and insulin sensitivity, from
visceral adipose (VAT) and SAT from 14 surgical patients and from
38 subjects with impaired glucose tolerance randomized to receive
either pioglitazone or metformin for 10 weeks. An adipocyte culture
system was also used to assess the effects of pioglitazone and coculture
with macrophages on TSP1 gene expression. RESULTS--TSP1 mRNA was
significantly associated with obesity (BMI) and insulin resistance
(low insulin sensitivity index). Relatively strong positive associations
were seen with markers of inflammation, including CD68, macrophage
chemoattractant protein-1, and plasminogen activator inhibitor (PAI)-1
mRNA (r [≥] 0.46, P = 0.001 for each), that remained significant
after controlling for BMI and Si. However, TSP1 mRNA was preferentially
expressed in adipocyte fraction, whereas inflammatory markers predominated
in stromal vascular fraction. Coculture of adipocytes and macrophages
augmented TSP1 gene expression and secretion from both cell types.
Pioglitazone (not metformin) treatment resulted in a 54% decrease
(P < 0.04) in adipose TSP gene expression, as did in vitro pioglitazone
treatment of adipocytes. CONCLUSIONS--TSP1 is a true adipokine that
is highly expressed in obese, insulin-resistant subjects; is highly
correlated with adipose inflammation; and is decreased by pioglitazone.
TSP1 is an important link between adipocytes and macrophage-driven
adipose tissue inflammation and may mediate the elevation of PAI-1
that promotes a prothrombotic state.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/57/2/432}
}
@ARTICLE{Varma2007,
author = {Varma, Vijayalakshmi and Yao-Borengasser, Aiwei and Rasouli, Neda
and Bodles, Angela M. and Phanavanh, Bounleut and Lee, Mi-Jeong and
Starks, Tasha and Kern, Leslie M. and Spencer, Horace J., III and
McGehee, Robert E., Jr. and Fried, Susan K. and Kern, Philip A.},
title = {Human Visfatin Expression: Relationship to Insulin Sensitivity, Intramyocellular
Lipids, and Inflammation},
journal = {J. Clin. Endocrinol. Metab.},
year = {2007},
volume = {92},
pages = {666--672},
number = {2},
month = feb,
abstract = {Context: Visfatin (VF) is a recently described adipokine preferentially
secreted by visceral adipose tissue (VAT) with insulin mimetic properties.
Objective: The aim of this study was to examine the association of
VF with insulin sensitivity, intramyocellular lipids (IMCL), and
inflammation in humans. Design and Patients: VF mRNA was examined
in paired samples of VAT and abdominal sc adipose tissue (SAT) obtained
from subjects undergoing surgery. Plasma VF and VF mRNA was also
examined in SAT and muscle tissue, obtained by biopsy from well-characterized
subjects with normal or impaired glucose tolerance, with a wide range
in body mass index (BMI) and insulin sensitivity (SI). Setting: The
study was conducted at a University Hospital and General Clinical
Research Center. Intervention: SI was measured, and fat and muscle
biopsies were performed. In impaired glucose tolerance subjects,
these procedures were performed before and after treatment with pioglitazone
or metformin. Main Outcome Measures: We measured the relationship
between VF and obesity, SI, adipose tissue inflammation, IMCL, and
response to insulin sensitizers. Results: No significant difference
in VF mRNA was seen between SAT and VAT depots. VAT VF mRNA associated
positively with BMI, whereas SAT VF mRNA decreased with BMI. SAT
VF correlated positively with SI, and the association of SAT VF mRNA
with SI was independent of BMI. IMCL and markers of inflammation
(adipose CD68 and plasma TNF{alpha}) were negatively associated with
SAT VF. Impaired glucose tolerance subjects treated with pioglitazone
showed no change in SAT VF mRNA despite a significant increase in
SI. Plasma VF and muscle VF mRNA did not correlate with BMI or SI
or IMCL, and there was no change in muscle VF with either pioglitazone
or metformin treatments. Conclusion: SAT VF is highly expressed in
lean, more insulinsensitive subjects and is attenuated in subjects
with high IMCL, low SI, and high levels of inflammatory markers.
VAT VF and SAT VF are regulated oppositely with BMI.},
url = {http://jcem.endojournals.org/cgi/content/abstract/92/2/666}
}
@ARTICLE{Varma2009,
author = {Varma, Vijayalakshmi and Yao-Borengasser, Aiwei and Rasouli, Neda
and Nolen, Greg T. and Phanavanh, Bounleut and Starks, Tasha and
Gurley, Cathy and Simpson, Pippa and McGehee, Robert E., Jr. and
Kern, Philip A. and Peterson, Charlotte A.},
title = {Muscle inflammatory response and insulin resistance: synergistic
interaction between macrophages and fatty acids leads to impaired
insulin action},
journal = {Am J Physiol Endocrinol Metab},
year = {2009},
volume = {296},
pages = {E1300--1310},
number = {6},
month = jun,
abstract = {Obesity is characterized by adipose tissue expansion as well as macrophage
infiltration of adipose tissue. This results in an increase in circulating
inflammatory cytokines and nonesterified fatty acids, factors that
cause skeletal muscle insulin resistance. Whether obesity also results
in skeletal muscle inflammation is not known. In this study, we quantified
macrophages immunohistochemically in vastus lateralis biopsies from
eight obese and eight lean subjects. Our study demonstrates that
macrophages infiltrate skeletal muscle in obesity, and we developed
an in vitro system to study this mechanistically. Myoblasts were
isolated from vastus lateralis biopsies and differentiated in culture.
Coculture of differentiated human myotubes with macrophages in the
presence of palmitic acid, to mimic an obese environment, revealed
that macrophages in the presence of palmitic acid synergistically
augment cytokine and chemokine expression in myotubes, decrease I{kappa}B-{alpha}
protein expression, increase phosphorylated JNK, decrease phosphorylated
Akt, and increase markers of muscle atrophy. These results suggest
that macrophages alter the inflammatory state of muscle cells in
an obese milieu, inhibiting insulin signaling. Thus in obesity both
adipose tissue and skeletal muscle inflammation may contribute to
insulin resistance.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/296/6/E1300}
}
@ARTICLE{Varsamos2006,
author = {Varsamos, Stamatis and Xuereb, Benoit and Commes, Therese and Flik,
Gert and Spanings-Pierrot, Celine},
title = {Pituitary hormone mRNA expression in European sea bass Dicentrarchus
labrax in seawater and following acclimation to fresh water},
journal = {J. Endocrinol.},
year = {2006},
volume = {191},
pages = {473--480},
number = {2},
month = nov,
abstract = {The mRNA expression of pituitary prolactin (prl), growth hormone (gh),
somatolactin (sl), proopiomelanocortin (pomc), and gonadotropins
(gthI and gthII) was quantified by real-time PCR, in sea bass, Dicentrarchus
labrax, adapted for 1 month to seawater (SW) or freshwater (FW).
In addition, IGF-I (igfI) mRNA expression in liver and branchial
Na+/K+-ATPase activity were determined. L17 ribosomal protein (rpL17)
and elongation factor 1{alpha} (ef1{alpha}) were validated as reference
genes in real-time PCR in the experimental context. The real-time
PCR assays were validated for the different hormone genes considered.
Expression of pituitary pomc, gthI, gthII, gh, and liver igfI was
not significantly different between FW and SW fish. Pituitary prlwas
4.5-foldhigher in FWthan in SW, whereas pituitary sl was 1.8-fold
higher in SW- compared with FW-adapted fish. Gill Na+/K+-ATPase specific
activity was 2.3-fold higher in FW sea bass compared with SW fish.
Plasma cortisol levels were 6.5-fold lower in SW- than in FW-adapted
specimens. The results are discussed in relation to the osmoregulatory
strategy of this euryhaline SW species, which displays features that
do not fit present models based on salmonids and FWeuryhaline teleosts.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/191/2/473}
}
@ARTICLE{Vartanian2009,
author = {Vartanian, Kristina and Slottke, Rachel and Johnstone, Timothy and
Casale, Amanda and Planck, Stephen and Choi, Dongseok and Smith,
Justine and Rosenbaum, James and Harrington, Christina},
title = {Gene expression profiling of whole blood: Comparison of target preparation
methods for accurate and reproducible microarray analysis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {2},
number = {1},
abstract = {BACKGROUND:Peripheral blood is an accessible and informative source
of transcriptomal information for many human disease and pharmacogenomic
studies. While there can be significant advantages to analyzing RNA
isolated from whole blood, particularly in clinical studies, the
preparation of samples for microarray analysis is complicated by
the need to minimize artifacts associated with highly abundant globin
RNA transcripts. The impact of globin RNA transcripts on expression
profiling data can potentially be reduced by using RNA preparation
and labeling methods that remove or block globin RNA during the microarray
assay. We compared four different methods for preparing microarray
hybridization targets from human whole blood collected in PAXGene
tubes. Three of the methods utilized the Affymetrix one-cycle cDNA
synthesis/in vitro transcription protocol but varied treatment of
input RNA as follows: i. no treatment; ii. treatment with GLOBINclear;
or iii. treatment with globin PNA oligos. In the fourth method cDNA
targets were prepared with the Ovation amplification and labeling
system.RESULTS:We find that microarray targets generated with labeling
methods that reduce globin mRNA levels or minimize the impact of
globin transcripts during hybridization detect more transcripts in
the microarray assay compared with the standard Affymetrix method.
Comparison of microarray results with quantitative PCR analysis of
a panel of genes from the NF-kappa B pathway shows good correlation
of transcript measurements produced with all four target preparation
methods, although method-specific differences in overall correlation
were observed. The impact of freezing blood collected in PAXGene
tubes on data reproducibility was also examined. Expression profiles
show little or no difference when RNA is extracted from either fresh
or frozen blood samples.CONCLUSION:RNA preparation and labeling methods
designed to reduce the impact of globin mRNA transcripts can significantly
improve the sensitivity of the DNA microarray expression profiling
assay for whole blood samples. While blockage of globin transcripts
during first strand cDNA synthesis with globin PNAs resulted in the
best overall performance in this study, we conclude that selection
of a protocol for expression profiling studies in blood should depend
on several factors, including implementation requirements of the
method and study design. RNA isolated from either freshly collected
or frozen blood samples stored in PAXGene tubes can be used without
altering gene expression profiles.},
doi = {10.1186/1471-2164-10-2},
issn = {1471-2164},
pubmedid = {19123946},
url = {http://www.biomedcentral.com/1471-2164/10/2}
}
@ARTICLE{Vartiainen2006,
author = {Vartiainen, Suvi and Pehkonen, Petri and Lakso, Merja and Nass, Richard
and Wong, Garry},
title = {Identification of gene expression changes in transgenic C. elegans
overexpressing human [alpha]-synuclein},
journal = {Neurobiology of Disease},
year = {2006},
volume = {22},
pages = {477--486},
number = {3},
month = jun,
abstract = {[alpha]-Synuclein containing cellular inclusions are a hallmark of
Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy.
A genome wide expression screen was performed in C. elegans overexpressing
both wild-type and A53T human [alpha]-synuclein. 433 genes were up-
and 67 genes down-regulated by statistical and fold change (> or
<2) criteria. Gene ontology (GO) categories within the regulated
gene lists indicated over-representation of development and reproduction,
mitochondria, catalytic activity, and histone groups. Seven genes
(pdr-1, ubc-7, pas-5, pas-7, pbs-4, RPT2, PSMD9) with function in
the ubiquitin-proteasome system and 35 mitochondrial function genes
were up-regulated. Nine genes that form histones H1, H2B, and H4
were down-regulated. These results demonstrate the effects of [alpha]-synuclein
on proteasome and mitochondrial complex gene expression and provide
further support for the role of these complexes in mediating neurotoxicity.
The results also indicate an effect on nuclear protein genes that
suggests a potential new avenue for investigation.},
issn = {0969-9961},
keywords = {[alpha]-Synuclein, C. elegans, Parkinson's disease, Microarray, Bioinformatics,
Clustering},
url = {http://www.sciencedirect.com/science/article/B6WNK-4JS208S-1/2/13dc3f17cb194b899342581a3833fc26}
}
@ARTICLE{Varticovski2007,
author = {Varticovski, Lyuba and Hollingshead, Melinda G. and Robles, Ana I.
and Wu, Xiaolin and Cherry, James and Munroe, David J. and Lukes,
Luanne and Anver, Miriam R. and Carter, John P. and Borgel, Suzanne
D. and Stotler, Howard and Bonomi, Carrie A. and Nunez, Nomeli P.
and Hursting, Stephen D. and Qiao, Wenhui and Deng, Chuxia X. and
Green, Jeff E. and Hunter, Kent W. and Merlino, Glenn and Steeg,
Patricia S. and Wakefield, Lalage M. and Barrett, J. Carl},
title = {Accelerated Preclinical Testing Using Transplanted Tumors from Genetically
Engineered Mouse Breast Cancer Models},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {2168--2177},
number = {7},
month = apr,
abstract = {Purpose: The use of genetically engineered mouse (GEM) models for
preclinical testing of anticancer therapies is hampered by variable
tumor latency, incomplete penetrance, and complicated breeding schemes.
Here, we describe and validate a transplantation strategy that circumvents
some of these difficulties. Experimental Design: Tumor fragments
from tumor-bearing MMTV-PyMT or cell suspensions from MMTV-PyMT,
-Her2/neu, -wnt1, -wnt1/p53+/-, BRCA1/p53+/-, and C3(1)T-Ag mice
were transplanted into the mammary fat pad or s.c. into naive syngeneic
or immunosuppressed mice. Tumor development was monitored and tissues
were processed for histopathology and gene expression profiling.
Metastasis was scored 60 days after the removal of transplanted tumors.
Results: PyMT tumor fragments and cell suspensions from anterior
glands grew faster than posterior tumors in serial passages regardless
of the site of implantation. Microarray analysis revealed genetic
differences between these tumors. The transplantation was reproducible
using anterior tumors from multiple GEM, and tumor growth rate correlated
with the number of transplanted cells. Similar morphologic appearances
were observed in original and transplanted tumors. Metastasis developed
in >90% of mice transplanted with PyMT, 40% with BRCA1/p53+/- and
wnt1/p53+/-, and 15% with Her2/neu tumors. Expansion of PyMT and
wnt1 tumors by serial transplantation for two passages did not lead
to significant changes in gene expression. PyMT-transplanted tumors
and anterior tumors of transgenic mice showed similar sensitivities
to cyclophosphamide and paclitaxel. Conclusions: Transplantation
of GEM tumors can provide a large cohort of mice bearing mammary
tumors at the same stage of tumor development and with defined frequency
of metastasis in a well-characterized molecular and genetic background.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/7/2168}
}
@ARTICLE{Varty2004,
author = {Varty, LoriAnn M. and Gustafson, Eric and Laverty, Maureen and Hey,
John A.},
title = {Activation of histamine H3 receptors in human nasal mucosa inhibits
sympathetic vasoconstriction},
journal = {European Journal of Pharmacology},
year = {2004},
volume = {484},
pages = {83--89},
number = {1},
month = jan,
abstract = {The peripheral histamine H3 receptor is a presynaptic heterologous
receptor located on postganglionic sympathetic nerve fibers innervating
sympathetic effector systems such as blood vessels and the heart.
An extensive body of evidence shows that activation of the histamine
H3 receptor attenuates sympathetic tone by presynaptic inhibition
of noradrenaline release. It is proposed that this sympathoinhibitory
action, in vivo, leads to reduced vasoconstriction, thereby eliciting
a vasodilatory effect. In humans, the peripheral histamine H3 receptor
has also been shown to exert a sympathoinhibitory function on specific
peripheral autonomic effector systems. For example, human saphenous
vein and heart possess functional presynaptic histamine H3 receptors
on the sympathetic nerve terminals that upon activation decrease
the sympathetic tone to these respective organs. The present studies
were conducted to define the role of histamine H3 receptors on neurogenic
sympathetic vasoconstrictor responses in human nasal turbinate mucosa.
Contractility studies were conducted to evaluate the effect of histamine
H3 receptor activation on sympathetic vasoconstriction in surgically
isolated human nasal turbinate mucosa. We found that the histamine
H3 receptor agonist, (R)-[alpha]-methylhistamine (30 and 300 nM),
inhibited electrical field stimulation-induced (neurogenic) sympathetic
vasoconstriction in a concentration-dependent fashion. Pretreatment
with the selective histamine H3 receptor antagonist, clobenpropit
(100 nM), blocked the sympathoinhibitory effect of (R)-[alpha]-methylhistamine
on the neurogenic sympathetic vasoconstriction. In addition, analysis
of Taqman mRNA expression studies showed a specific, high level of
distribution of the histamine H3 receptor localized in the human
nasal mucosa. Taken together, these studies indicate that histamine
H3 receptors modulate vascular contractile responses in human nasal
mucosa most likely by inhibiting noradrenaline release from sympathetic
nerve terminals in nasal mucosa. It is further suggested that histamine
H3 receptors may play a role in the regulation of vascular tone and
nasal patency in histamine-dependent allergic nasal congestive disease.},
issn = {0014-2999},
keywords = {Histamine H3 receptor, Nasal mucosa, human, Sympathetic, Taqman},
url = {http://www.sciencedirect.com/science/article/B6T1J-4B6KMX0-1/2/d2de22ef13fc7ad1fdb6872a60e63c9b}
}
@ARTICLE{Vasconcellos2011,
author = {de Vasconcellos, JaÃra Ferreira and Laranjeira, Angelo Brunelli
Albertoni and Zanchin, Nilson Ivo Tonin and Otubo, Rosemary and Vaz,
Thais Haline and Cardoso, Angelo Almeida and Brandalise, Silvia Regina
and Yunes, José Andrés},
title = {Increased CCL2 and IL-8 in the bone marrow microenvironment in acute
lymphoblastic leukemia},
journal = {Pediatric Blood \& Cancer},
year = {2011},
volume = {56},
pages = {568--577},
number = {4},
abstract = {Abstract BackgroundThe interactions of acute lymphoblastic leukemia
(ALL) blasts with bone marrow (BM) stromal cells have a positive
impact on leukemia cell survival. In the present study, we proposed
to identify and investigate the role of molecules critically involved
in leukemia—microenvironment crosstalk.ProcedureGene expression
profiling analyses of BM mesenchymal stem cells (BMMSC) were performed
following stimulation by ALL cells. CCL2 and IL-8 plasma levels were
evaluated from ALL patients and controls. Expression of the CCL2
and IL-8 receptors in ALL was determined by RT-PCR. The biological
effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B
ALL and BMMSC cells were evaluated using in vitro assays.ResultsLeukemia
stimulation of BMMSC upregulated the expression of several inflammatory
chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2
and IL-8 in children at diagnosis were significantly higher than
in healthy controls (P < 0.001). Functional studies revealed
that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion
of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival
and to increase their proliferation. ALL cells were not directly
affected by CCL2 or IL-8.ConclusionsThe leukemic BM microenvironment
had increased levels of CCL2 and IL-8. These chemokines are known
to have suppressive effects in normal hematopoiesis. Our data indicate
that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation,
and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8
upregulation may represent one possible mechanism of microenvironment
perversion in favor of ALL cells. Pediatr Blood Cancer 2011;56:568–577.
© 2010 Wiley-Liss, Inc.},
doi = {10.1002/pbc.22941},
issn = {1545-5017},
keywords = {acute lymphoblastic leukemia, bone marrow microenvironment, CCL2,
IL-8},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pbc.22941}
}
@ARTICLE{Vasconcelos2011,
author = {Vasconcelos, Nivaldo and Pantoja, Janaina and Belchior, Hindiael
and Caixeta, Fabio Viegas and Faber, Jean and Freire, Marco Aurelio
M. and Cota, Vinicius Rosa and Anibal de Macedo, Edson and Laplagne,
Diego A. and Gomes, Herman Martins and Ribeiro, Sidarta},
title = {Cross-modal responses in the primary visual cortex encode complex
objects and correlate with tactile discrimination},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {15408-15413},
number = {37},
abstract = {Cortical areas that directly receive sensory inputs from the thalamus
were long thought to be exclusively dedicated to a single modality,
originating separate labeled lines. In the past decade, however,
several independent lines of research have demonstrated cross-modal
responses in primary sensory areas. To investigate whether these
responses represent behaviorally relevant information, we carried
out neuronal recordings in the primary somatosensory cortex (S1)
and primary visual cortex (V1) of rats as they performed whisker-based
tasks in the dark. During the free exploration of novel objects,
V1 and S1 responses carried comparable amounts of information about
object identity. During execution of an aperture tactile discrimination
task, tactile recruitment was slower and less robust in V1 than in
S1. However, V1 tactile responses correlated significantly with performance
across sessions. Altogether, the results support the notion that
primary sensory areas have a preference for a given modality but
can engage in meaningful cross-modal processing depending on task
demand.},
doi = {10.1073/pnas.1102780108},
eprint = {http://www.pnas.org/cgi/reprint/108/37/15408.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/37/15408}
}
@ARTICLE{Vascotto2009,
author = {Vascotto, Carlo and Cesaratto, Laura and Zeef, Leo A. H. and Deganuto,
Marta and D'Ambrosio, Chiara and Scaloni, Andrea and Romanello, Milena
and Damante, Giuseppe and Taglialatela, Giulio and Delneri, Daniela
and Kelley, Mark R. and Mitra, Sankar and Quadrifoglio, Franco and
Tell, Gianluca},
title = {Genome-wide analysis and proteomic studies reveal APE1/Ref-1 multifunctional
role in mammalian cells},
journal = {Proteomics},
year = {2009},
volume = {9},
pages = {1058--1074},
number = {4},
abstract = {Abstract Apurinic apyrimidinic endonuclease/redox effector factor
1 (APE1/Ref-1) protects cells from oxidative stress by acting as
a central enzyme in base excision repair pathways of DNA lesions
and through its independent activity as a redox transcriptional co-activator.
Dysregulation of this protein has been associated with cancer development.
At present, contrasting data have been published regarding the biological
relevance of the two functions as well as the molecular mechanisms
involved. Here, we combined both mRNA expression profiling and proteomic
analysis to determine the molecular changes associated with APE1
loss-of-expression induced by siRNA technology. This approach identified
a role of APE1 in cell growth, apoptosis, intracellular redox state,
mitochondrial function, and cytoskeletal structure. Overall, our
data show that APE1 acts as a hub in coordinating different and vital
functions in mammalian cells, highlighting the molecular determinants
of the multifunctional nature of APE1 protein.},
issn = {1615-9861},
keywords = {APE1, Apoptosis, Oxidative stress, Ref-1, siRNA},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200800638}
}
@ARTICLE{Vasikova2010,
author = {Vasikova, Alzbeta and Belickova, Monika and Budinska, Eva and Cermak,
Jaroslav},
title = {A distinct expression of various gene subsets in CD34+ cells from
patients with early and advanced myelodysplastic syndrome},
journal = {Leukemia Research},
year = {2010},
volume = {34},
pages = {1566--1572},
number = {12},
month = dec,
abstract = {Gene expression profiles of CD34+ cells were compared between 51 MDS
patients and 7 controls. The most up-regulated genes in patients
included HBG2, HBG1, CYBRD1, HSPA1B, ANGPT, and MYC, while 13 genes
related to B-lymphopoiesis showed down-regulation. We observed in
advanced MDS patients decreased expression of genes involved in cell
cycle control, DNA repair and increased expression of proto-oncogenes,
angiogenic and anti-apoptic genes. The results suggest that increased
cell proliferation and resistance to apoptosis together with a loss
of cell cycle control, damaged DNA repair and altered immune response
may play an important role in malignant clone expansion in MDS.},
issn = {0145-2126},
keywords = {Myelodysplastic syndrome, Acute myeloid leukemia, Gene expression
profiling, Microarray, CD34+ cells},
url = {http://www.sciencedirect.com/science/article/B6T98-4YR49XK-1/2/8f6d244042ca321e23aa86ca8d8abfbf}
}
@ARTICLE{Vasilache2007,
author = {Vasilache, Ana Maria and Andersson, Josefin and Nilsberth, Camilla},
title = {Expression of PGE2 EP3 receptor subtypes in the mouse preoptic region},
journal = {Neuroscience Letters},
year = {2007},
volume = {423},
pages = {179--183},
number = {3},
month = aug,
abstract = {Inflammatory-induced fever is dependent on prostaglandin E2 (PGE2)
binding to its EP3 receptor in the thermoregulatory region of the
hypothalamus, but it is not known which EP3 receptor isoform(s) that
is/are involved. We identified the EP3 receptor expression in the
mouse preoptic region by in situ hybridization and isolated the corresponding
area by laser capture microdissection. Real-time RT-PCR analysis
of microdissected tissue revealed a predominant expression of the
EP3[alpha] isoform, but there was also considerable expression of
EP3[gamma], corresponding to approximately 15% of total EP3 receptor
expression, whereas EP3[beta] was sparsely expressed. This distribution
was not changed by immune challenge induced by peripheral administration
of LPS, indicating that EP3 receptor splicing and distribution is
not activity dependent. Considering that EP3[alpha] and EP3[gamma]
are associated with inhibitory and stimulatory G-proteins, respectively,
the present data demonstrate that the PGE2 response of the target
neurons is intricately regulated.},
issn = {0304-3940},
keywords = {Prostaglandin E2, Real-time RT-PCR, EP3 receptor isoform, Fever, Laser
capture microdissection, Mouse, Preoptic region},
url = {http://www.sciencedirect.com/science/article/B6T0G-4P7X4RX-2/2/21b8c621014ac85309b14fce557fce63}
}
@ARTICLE{Vasilyeva2004,
author = {Vasilyeva, E and Woodard, J and Taylor, FR and Kretschmer, M and
Fajardo, H and Lyubarskaya, Y and Kobayashi, K and Dingley, A and
Mhatre, R},
title = {Development of a chip-based capillary gel electrophoresis method
for quantification of a half-antibody in immunoglobulin G4 samples.},
journal = {Electrophoresis},
year = {2004},
volume = {25},
pages = {3890-6--},
number = {21-22},
month = nov,
abstract = {A method based on microfluidic technology was developed to support
quantitative analysis of recombinant monoclonal immunoglobulin G4
(IgG4) antibody samples. The assay was performed on an Agilent 2100
Bioanalyzer in combination with the Protein 200 Plus LabChip Kit
and the Protein 200 Plus assay software. Capillary electrophoresis
principles have been transferred to a chip format that integrates
all separation, staining, virtual destaining, and detection steps.
The method is referred to in this paper as chip-based capillary gel
electrophoresis (GelChip-CE method). The GelChip-CE method under
nonreducing conditions proved to be a quantitative test for half-antibody
determination in IgG4 samples. Similar to the traditional nonreducing
sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
method, the GelChip-CE method includes a denaturing step prior to
separation. We showed that denaturing the sample by heating resulted
in an artificial increase in the amount of half-antibody detected,
which could be prevented by addition of N-ethylmaleimide to the sample
buffer. The GelChip-CE method allowed for analysis of IgG4 samples
with more accuracy, higher precision, and a faster turnaround time
than SDS-PAGE and reversed-phase high-performance liquid chromatography
(RP-HPLC).},
url = {http://www.biomedexperts.com/Abstract.bme/15565674/Development_of_a_chip-based_capillary_gel_electrophoresis_method_for_quantification_of_a_half-antibody_in_immunoglobulin}
}
@ARTICLE{Vasko2007,
author = {Vasko, Vasily and Espinosa, Allan V. and Scouten, William and He,
Huiling and Auer, Herbert and Liyanarachchi, Sandya and Larin, Alexander
and Savchenko, Victoria and Francis, Gary L. and de la Chapelle,
Albert and Saji, Motoyasu and Ringel, Matthew D.},
title = {Gene expression and functional evidence of epithelial-to-mesenchymal
transition in papillary thyroid carcinoma invasion},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {2803--2808},
number = {8},
month = feb,
abstract = {Papillary thyroid carcinomas (PTCs) that invade into local structures
are associated with a poor prognosis, but the mechanisms for PTC
invasion are incompletely defined, limiting the development of new
therapies. To characterize biological processes involved in PTC invasion,
we analyzed the gene expression profiles of microscopically dissected
intratumoral samples from central and invasive regions of seven widely
invasive PTCs and normal thyroid tissue by oligonucleotide microarray
and performed confirmatory expression and functional studies. In
comparison with the central regions of primary PTCs, the invasive
fronts overexpressed TGF [beta], NF{kappa}B and integrin pathway
members, and regulators of small G proteins and CDC42. Moreover,
reduced levels of mRNAs encoding proteins involved in cell-cell adhesion
and communication were identified, consistent with epithelial-to-mesenchymal
transition (EMT). To confirm that aggressive PTCs were characterized
by EMT, 34 additional PTCs were examined for expression of vimentin,
a hallmark of EMT. Overexpression of vimentin was associated with
PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated
that vimentin was required both for the development and maintenance
of a mesenchymal morphology and invasiveness in thyroid cancer cells.
We conclude that EMT is common in PTC invasion and that vimentin
regulates thyroid cancer EMT in vitro.},
url = {http://www.pnas.org/cgi/content/abstract/104/8/2803}
}
@ARTICLE{Vass2006,
author = {Vass, Laura and Kis, Zoltán and Fehér, Liliána Z. and Zvara,
�gnes and Lőrincz, Zsolt and Borbola, Ildikó and Cseh, Sándor
and Kulin, Sándor and Ürge, László and Dormán, György and Puskás,
László G.},
title = {Medium-Throughput Microarray-Based Approach for Toxicogenomic Profiling
of Small Molecules},
journal = {QSAR Comb. Sci.},
year = {2006},
volume = {25},
pages = {1039--1046},
number = {11},
abstract = {Abstract 10.1002/qsar.200640079.abs Investigating the interaction
between small molecules and cells by DNA-microarrays or in human
type phenotypic assays is very labor-intensive and expensive, therefore
such parallel characterization of large compound libraries is currently
economically not feasible. Therefore, we developed our own ToxicoScreenTM
microarrays, consisting of 48 subarrays, for medium-throughput analysis.
Each subarray can be individually addressed and has probes for genes
coding ABC transporters, carbohydrate sulfotransferases, cytochrome
P450, glutathione S-transferases, UDP-glucosyltransferases, heat-shock
proteins, acyl-coenzyme A oxidases, receptors, and metallothioneins.
Microarray analysis was performed in an array-in-array format which
enabled us to screen 8–24 compounds per microarray providing 6–2
replica results in one hybridization step. To validate our platform,
gene-expression changes in human hepatocarcinoma (HepG2) cells in
response to six toxic compounds were determined in eight replica
experiments. Two normalization strategies were tested. We found that
normalization to the total intensities of one subarray gave the best
result. Among 121 genes only two resulted in significantly non-relevant
data. We found general toxicology markers such as ABC transporters,
lipase A, growth arrest and DNA damage-inducible alpha, PPARα, and
glutathione S-transferase theta 1 and M1. The developed microarray
platform can be used to assess the possible toxic side effects of
certain drug candidates and to determine fingerprints as well.},
issn = {1611-0218},
keywords = {DNA-microarray, toxicogenomics, ABC-transporters, screening},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/qsar.200640079}
}
@ARTICLE{Vassallo2010,
author = {Vassallo, Robert and Walters, Paula and Lamont, Jeffrey and Kottom,
Theodore and Yi, Eunhee and Limper, Andrew},
title = {Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung
Tissue Research Consortium study},
journal = {Respiratory Research},
year = {2010},
volume = {11},
pages = {45},
number = {1},
abstract = {BACKGROUND:Abnormal immune responses are believed to be highly relevant
in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Dendritic cells provide a critical checkpoint for immunity by their
capacity to both induce and suppress immunity. Although evident that
cigarette smoke, the primary cause of COPD, significantly influences
dendritic cell functions, little is known about the roles of dendritic
cells in the pathogenesis of COPD.METHODS:The extent of dendritic
cell infiltration in COPD tissue specimens was determined using immunohistochemical
localization of CD83+ cells (marker of matured myeloid dendritic
cells), and CD1a+ cells (Langerhans cells). The extent of tissue
infiltration with Langerhans cells was also determined by the relative
expression of the CD207 gene in COPD versus control tissues. To determine
mechanisms by which dendritic cells accumulate in COPD, complimentary
studies were conducted using monocyte-derived human dendritic cells
exposed to cigarette smoke extract (CSE), and dendritic cells extracted
from mice chronically exposed to cigarette smoke.RESULTS:In human
COPD lung tissue, we detected a significant increase in the total
number of CD83+ cells, and significantly higher amounts of CD207
mRNA when compared with control tissue. Human monocyte-derived dendritic
cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro
when compared with control dendritic cells. Murine dendritic cells
extracted from mice exposed to cigarette smoke for 4 weeks, also
demonstrated enhanced survival compared to dendritic cells extracted
from control mice. Acute exposure of human dendritic cells to CSE
induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1),
and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through
oxidative stress. Although activated human dendritic cells conditioned
with CSE expressed diminished migratory CCR7 expression, their migration
towards the CCR7 ligand CCL21 was not impaired.CONCLUSIONS:These
data indicate that COPD is associated with increased numbers of cells
bearing markers associated with Langerhans cells and mature dendritic
cells, and that cigarette smoke promotes survival signals and augments
survival of dendritic cells. Although CSE suppressed dendritic cell
CCR7 expression, migration towards a CCR7 ligand was not diminished,
suggesting that reduced CCR7-dependent migration is unlikely to be
an important mechanism for dendritic cell retention in the lungs
of smokers with COPD.},
doi = {10.1186/1465-9921-11-45},
issn = {1465-9921},
pubmedid = {20420706},
url = {http://respiratory-research.com/content/11/1/45}
}
@ARTICLE{Vatakis2009,
author = {Vatakis, Dimitrios N. and Kim, Sanggu and Kim, Namshin and Chow,
Samson A. and Zack, Jerome A.},
title = {Human Immunodeficiency Virus Integration Efficiency and Site Selection
in Quiescent CD4+ T Cells},
journal = {J. Virol.},
year = {2009},
volume = {83},
pages = {6222--6233},
number = {12},
month = jun,
abstract = {Until very recently, quiescent CD4+ T cells were thought to be resistant
to human immunodeficiency virus (HIV) infection. Subsequent studies,
attempting to fully elucidate the mechanisms of resistance, showed
that quiescent cells could become infected by HIV at low efficiency
and form a latently infected population. In this study, we set out
to identify the sites of viral integration and to assess the efficiency
of the overall integration process in quiescent cells. Based on our
results, HIV integration in quiescent CD4+ T cells occurs in sites
similar to those of their prestimulated counterparts. While site
selections are similar, the integration process in quiescent cells
is plagued by the formation of high levels of incorrectly processed
viral ends and abortive two-long-terminal-repeat circles.},
url = {http://jvi.asm.org/cgi/content/abstract/83/12/6222}
}
@ARTICLE{Vatamaniuk2006,
author = {Vatamaniuk, Marko Z. and Gupta, Rana K. and Lantz, Kristen A. and
Doliba, Nicolai M. and Matschinsky, Franz M. and Kaestner, Klaus
H.},
title = {Foxa1-Deficient Mice Exhibit Impaired Insulin Secretion due to Uncoupled
Oxidative Phosphorylation},
journal = {Diabetes},
year = {2006},
volume = {55},
pages = {2730--2736},
number = {10},
month = oct,
abstract = {Foxa1 (formerly hepatic nuclear factor 3{alpha}) belongs to the family
of Foxa genes that are expressed in early development and takes part
in the differentiation of endoderm-derived organs and the regulation
of glucose homeostasis. Foxa1-/- pups are growth retarded and hypoglycemic
but glucose intolerant in response to an intraperitoneal glucose
challenge. However, the mechanism of glucose intolerance in this
model has not been investigated. Here, we show that Foxa1-/- islets
exhibit decreased glucose-stimulated insulin release in islet perifusion
experiments and have significantly reduced pancreatic insulin and
glucagon content. Moreover, Foxa1-/- {beta}-cells exhibit attenuated
calcium influx in response to glucose and glyburide, suggesting an
insulin secretion defect either at the level or upstream of the ATP-sensitive
K+ channel. Intracellular ATP levels after incubation with 10 mmol/l
glucose were about 2.5 times lower in Foxa1-/- islets compared with
controls. This diminished ATP synthesis could be explained by increased
expression of the mitochondrial uncoupling protein uncoupling protein
2 (UCP2) in Foxa1-deficient islets, resulting in partially uncoupled
mitochondria. Chromatin immunoprecipitation assays indicate that
UCP2 is a direct transcriptional target of Foxa1 in vivo. Thus, we
have identified a novel function for Foxa1 in the regulation of oxidative
phosphorylation in pancreatic {beta}-cells.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/55/10/2730}
}
@ARTICLE{Vaughn2011,
author = {Vaughn, Laura M. and Masson, Patrick H. and Andrews, Brenda J.},
title = {A QTL Study for Regions Contributing to Arabidopsis thaliana Root
Skewing on Tilted Surfaces},
journal = {g3},
year = {2011},
volume = {1},
pages = {105-115},
number = {2},
abstract = {Plant root systems must grow in a manner that is dictated by endogenous
genetic pathways, yet sensitive to environmental input. This allows
them to provide the plant with water and nutrients while navigating
a heterogeneous soil environment filled with obstacles, toxins, and
pests. Gravity and touch, which constitute important cues for roots
growing in soil, have been shown to modulate root architecture by
altering growth patterns. This is illustrated by Arabidopsis thaliana
roots growing on tilted hard agar surfaces. Under these conditions,
the roots are exposed to both gravity and touch stimulation. Consequently,
they tend to skew their growth away from the vertical and wave along
the surface. This complex growth behavior is believed to help roots
avoid obstacles in nature. Interestingly, A. thaliana accessions
display distinct growth patterns under these conditions, suggesting
the possibility of using this variation as a tool to identify the
molecular mechanisms that modulate root behavior in response to their
mechanical environment. We have used the Cvi/Ler recombinant inbred
line population to identify quantitative trait loci that contribute
to root skewing on tilted hard agar surfaces. A combination of fine
mapping for one of these QTL and microarray analysis of expression
differences between Cvi and Ler root tips identifies a region on
chromosome 2 as contributing to root skewing on tilted surfaces,
potentially by modulating cell wall composition.},
doi = {10.1534/g3.111.000331},
eprint = {http://www.g3journal.org/cgi/reprint/1/2/105.pdf},
url = {http://www.g3journal.org/cgi/content/abstract/1/2/105}
}
@ARTICLE{Vaurs-BarriA¨re2009,
author = {Vaurs-Barrière, Catherine and Deville, Marlène and Sarret, Catherine
and Giraud, Geneviève and Des Portes, Vincent and Prats-Viñas,
José-Maria and De Michele, Giuseppe and Dan, Bernard and Brady,
Angela F. and Boespflug-Tanguy, Odile and Touraine, Renaud},
title = {Pelizaeus–Merzbacher–Like disease presentation of MCT8 mutated
male subjects},
journal = {Ann Neurol.},
year = {2009},
volume = {65},
pages = {114--118},
number = {1},
abstract = {Abstract 10.1002/ana.21579.abs Pelizaeus–Merzbacher Disease is an
X-linked hypomyelinatiing leukodystrophy. We report mutations in
the thyroid hormone transporter gene MCT8 in 11% of 53 families affected
by hypomyelinating leukodystrophies of unknown aetiology. The 12
MCT8 mutated patients express initially a Pelizaeus–Merzbacher-Like
disease phenotype with a latter unusual improvement of magnetic resonance
imaging white matter signal despite absence of clinical progression.
This observation underlines the interest of determining both free
T3 and free T4 serum concentrations to screen for MCT8 mutations
in young patients (<3 y) with a severe Pelizaeus–Merzbacher-Like
disease presentation or older severe mentally retarded male patients
with “hypomyelinated� regions. Ann Neurol 2009;65:114–118},
issn = {1531-8249},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ana.21579}
}
@ARTICLE{Vawter2004,
author = {Vawter, Marquis P. and Ferran, Erick and Galke, Brandi and Cooper,
Kathleen and Bunney, William E. and Byerley, William},
title = {Microarray screening of lymphocyte gene expression differences in
a multiplex schizophrenia pedigree},
journal = {Schizophrenia Research},
year = {2004},
volume = {67},
pages = {41--52},
number = {1},
month = mar,
issn = {0920-9964},
keywords = {Transformed lymphocytes, Microarray, Gene expression, GNAO1, NPY1R,
MDH1, Real-time PCR},
url = {http://www.sciencedirect.com/science/article/B6TC2-4950C27-1/2/04b95ef81e62897c269953360a35d9ff}
}
@ARTICLE{Vawter2007,
author = {Vawter, Marquis P. and Harvey, Philip D. and DeLisi, Lynn E.},
title = {Dysregulation of X-linked gene expression in Klinefelter's syndrome
and association with verbal cognition},
journal = {Am. J. Med. Genet.},
year = {2007},
volume = {144B},
pages = {728--734},
number = {6},
abstract = {Abstract 10.1002/ajmg.b.30454.abs Klinefelter's Syndrome (KS) is a
chromosomal karyotype with one or more extra X chromosomes. KS individuals
often show language impairment and the phenotype might be due to
overexpression of genes on the extra X chromosome(s). We profiled
mRNA derived from lymphoblastoid cell lines from males with documented
KS and control males using the Affymetrix U133P microarray platform.
There were 129 differentially expressed genes (DEGs) in KS group
compared with controls after Benjamini–Hochberg false discovery
adjustment. The DEGs included 14 X chromosome genes which were significantly
over-represented. The Y chromosome had zero DEGs. In exploratory
analysis of gene expression–cognition relationships, 12 DEGs showed
significant correlation of expression with measures of verbal cognition
in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding
protein 6, putative) was inversely correlated with verbal IQ (r = −0.86,
P < 0.001) and four other measures of verbal ability. Overexpression
of XIST was found in KS compared to XY controls suggesting that silencing
of many genes on the X chromosome might occur in KS similar to XX
females. The microarray findings for eight DEGs were validated by
quantitative PCR. The 14 X chromosome DEGs were not differentially
expressed in prior studies comparing female and male brains suggesting
a dysregulation profile unique to KS. Examination of X-linked DEGs,
such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition–gene
expression correlations may establish a causal link between these
genes, neurodevelopment, and language function. A screen of candidate
genes may serve as biomarkers of KS for early diagnosis. © 2007
Wiley-Liss, Inc.},
issn = {1552-485X},
keywords = {XXY, XY, brain, lymphocytes, microarray, XIST, GTPBP6, TAF9L, CXORF21},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.30454}
}
@ARTICLE{Vazquez2011,
author = {Edward Vazquez and Amar A. Sethi and Lita Freeman and Gloria Zalos
and Hira Chaudhry and Erin Haser and Brittany O. Aicher and Angel
Aponte and Marjan Gucek and Gregory J. Kato and Myron A. Waclawiw
and Alan T. Remaley and Richard O. Cannon III},
title = {High-Density Lipoprotein Cholesterol Efflux, Nitration of Apolipoprotein
A-I, and Endothelial Function in Obese Women},
journal = {The American Journal of Cardiology},
year = {2011},
pages = { - },
number = {0},
abstract = {Subjects at risk of atherosclerosis might have dysfunctional high-density
lipoprotein (HDL) despite normal cholesterol content in the plasma.
We considered whether the efflux of excess cellular cholesterol to
HDL from obese subjects is associated with impaired arterial endothelial
function, a biomarker of cardiovascular risk. A total of 54 overweight
(body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI ≥30 kg/m2)
women, aged 46 ± 11 years, were enrolled in a worksite wellness
program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely
associated with the BMI (r = −0.419, p = 0.002). Endothelial function
was assessed using brachial artery flow-mediated dilation. Cholesterol
efflux from 3H-cholesterol–labeled baby hamster kidney cells transfected
with the adenosine triphosphate-binding cassette transporter 1 showed
8.2% to 22.5% cholesterol efflux within 18 hours when incubated with
1% serum and was positively correlated with brachial artery flow-mediated
dilation (p <0.05), especially in the 34 subjects with BMI ≥30
kg/m2 (r = 0.482, p = 0.004). This relation was independent of age,
HDL or low-density lipoprotein cholesterol concentrations in plasma,
blood pressure, or insulin resistance on stepwise multiple regression
analysis (β = 0.31, R2 = 0.21, p = 0.007). Nitration of apolipoprotein
A-I tyrosine residues (using sandwich enzyme-linked immunosorbent
assay) was significantly greater in women with a BMI ≥30 kg/m2
and the lowest cholesterol efflux than in women with a BMI of 25
to 29.9 kg/m2 and the greatest cholesterol efflux (p = 0.01). In
conclusion, we have shown that decreased cholesterol efflux by way
of the adenosine triphosphate-binding cassette transporter 1 is associated
with increased nitration of apolipoprotein A-I in HDL and is an independent
predictor of impaired endothelial function in women with a BMI of
≥30 kg/m2. This finding suggests that the functional measures of
HDL might be better markers for cardiovascular risk than the HDL
cholesterol levels in this population.},
doi = {10.1016/j.amjcard.2011.10.008},
issn = {0002-9149},
url = {http://www.sciencedirect.com/science/article/pii/S0002914911030451}
}
@ARTICLE{Vazquez-Chona2004,
author = {Vazquez-Chona, Felix and Song, Bong K. and Geisert, Eldon E., Jr},
title = {Temporal Changes in Gene Expression after Injury in the Rat Retina},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2004},
volume = {45},
pages = {2737--2746},
number = {8},
month = aug,
abstract = {PURPOSE. The goal of this study was to define the temporal changes
in gene expression after retinal injury and to relate these changes
to the inflammatory and reactive response. A specific emphasis was
placed on the tetraspanin family of proteins and their relationship
with markers of reactive gliosis. METHODS. Retinal tears were induced
in adult rats by scraping the retina with a needle. After different
survival times (4 hours, and 1, 3, 7, and 30 days), the retinas were
removed, and mRNA was isolated, prepared, and hybridized to the Affymatrix
RG-U34A microarray (Santa Clara, CA). Microarray results were confirmed
by using RT-PCR and correlation to protein levels was determined.
RESULTS. Of the 8750 genes analyzed, approximately 393 (4.5%) were
differentially expressed. Clustering analysis revealed three major
profiles: (1) The early response was characterized by the upregulation
of transcription factors; (2) the delayed response included a high
percentage of genes related to cell cycle and cell death; and (3)
the late, sustained profile clustered a significant number of genes
involved in retinal gliosis. The late, sustained cluster also contained
the upregulated crystallin genes. The tetraspanins Cd9, Cd81, and
Cd82 were also associated with the late, sustained response. CONCLUSIONS.
The use of microarray technology enables definition of complex genetic
changes underlying distinct phases of the cellular response to retinal
injury. The early response clusters genes associate with the transcriptional
regulation of the wound-healing process and cell death. Most of the
genes in the late, sustained response appear to be associated with
reactive gliosis.},
url = {http://www.iovs.org/cgi/content/abstract/45/8/2737}
}
@ARTICLE{Vecchio2010,
author = {Vecchio, D and Neglia, G and Di Palo, R and Campanile, G and Balestrieri,
ML and Giovane, A and Killian, G and Zicarelli, L and Gasparrini,
B},
title = {Ion, Protein, Phospholipid and Energy Substrate Content of Oviduct
Fluid During the Oestrous Cycle of Buffalo (Bubalus bubalis)},
journal = {Reproduction in Domestic Animals},
year = {2010},
volume = {45},
pages = {e32--e39},
number = {5},
abstract = {Contents The aim of this research was to analyse the composition of
oviduct fluid (ODF) in buffalo cows at different oestrous cycle phases
to fulfil the requirements of buffalo embryos in vitro. ODF was collected
by chronic cannulation from three cows that were synchronized by
administering a synthetic prostaglandin. Based on hormonal profiles,
the pre-ovulatory, ovulatory, post-ovulatory and luteal phases of
the oestrous cycle were defined. The volume of ODF produced (ml/24Â h)
was influenced by the oestrous cycle, with values (mean ± SE)
around ovulation (1.0 ± 0.2) greater (p < 0.05) than in both
the luteal (0.4 ± 0.1) and the post-ovulatory phases (0.5 ± 0.1),
but not different from the intermediate values in the pre-ovulatory
phase (0.8 ± 0.2). Among cycle phases, no differences were found
in sodium, potassium, calcium and magnesium concentrations (130.0 ± 1.1,
5.1 ± 0.3, 2.8 ± 0.1 and 0.59 ± 0.04 mmol/l respectively).
Interestingly, the chloride secretion (μm/24 h) was higher (p < 0.05)
at ovulation (150.2 ± 16.5) than during both the luteal (73.7 ± 22.0)
and the post-ovulatory phases (63.7 ± 11.2), with intermediate
values in the pre-ovulatory phase (113.4 ± 23.5). Glucose concentration
(mmol/l) was higher (p = 0.056) in the pre-ovulatory phase (0.06 ± 0.02)
than in the luteal (0.02 ± 0.01) and post-ovulatory (0.02 ± 0.01)
phases but not different from values in the ovulatory phase (0.04 ± 0.02).
Concentrations of pyruvate and lactate among oestrous cycle phases
were similar (0.08 ± 0.01 and 1.0 ± 0.1 mmol/l respectively).
The total quantity of phospholipids (μmol/24 h) was greater (p < 0.05)
at ovulation (0.21 ± 0.02) compared with the luteal, pre-ovulatory
and post-ovulatory phases of the cycle (0.09 ± 0.02, 0.13 ± 0.02
and 0.09 ± 0.01 respectively). No differences were found in either
the protein concentration (1.8 ± 0.3 mg/ml) or the quantity of
proteins secreted in 24 h (1.8 ± 0.4 mg) among oestrous cycle
phases. In conclusion, this study provides the first characterization
of buffalo ODF during the oestrous cycle, showing species-specific
differences that may be useful for developing suitable media for
buffalo in vitro embryo production.},
issn = {1439-0531},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0531.2009.01518.x}
}
@ARTICLE{Vedell2011,
author = {Vedell, Peter and Svenson, Karen and Churchill, Gary},
title = {Stochastic variation of transcript abundance in C57BL/6J mice},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {167},
number = {1},
abstract = {BACKGROUND:Transcripts can exhibit significant variation in tissue
samples from inbred laboratory mice. We have designed and carried
out a microarray experiment to examine transcript variation across
samples from adipose, heart, kidney, and liver tissues of C57BL/6J
mice and to partition variation into within-mouse and between-mouse
components. Within-mouse variance captures variation due to heterogeneity
of gene expression within tissues, RNA-extraction, and array processing.
Between-mouse variance reflects differences in transcript abundance
between genetically identical mice.RESULTS:The nature and extent
of transcript variation differs across tissues. Adipose has the largest
total variance and the largest within-mouse variance. Liver has the
smallest total variance, but it has the most between-mouse variance.
Genes with high variability can be classified into groups with correlated
patterns of expression that are enriched for specific biological
functions. Variation between mice is associated with circadian rhythm,
growth hormone signaling, immune response, androgen regulation, lipid
metabolism, and the extracellular matrix. Genes showing correlated
patterns of within-mouse variation are also associated with biological
functions that largely reflect heterogeneity of cell types within
tissues.CONCLUSIONS:Genetically identical mice can experience different
individual outcomes for medically important traits. Variation in
gene expression observed between genetically identical mice can identify
functional classes of genes that are likely to vary in the absence
of experimental perturbations, can inform experimental design decisions,
and provides a baseline for the interpretation of gene expression
data in interventional studies. The extent of transcript variation
among genetically identical mice underscores the importance of stochastic
and micro-environmental factors and their phenotypic consequences.},
doi = {10.1186/1471-2164-12-167},
issn = {1471-2164},
pubmedid = {21450099},
url = {http://www.biomedcentral.com/1471-2164/12/167}
}
@ARTICLE{Veen2010,
author = {van der Veen, Stijn and van Schalkwijk, Saskia and Molenaar, Douwe
and de Vos, Willem M. and Abee, Tjakko and Wells-Bennik, Marjon H.
J.},
title = {The SOS response of Listeria monocytogenes is involved in stress
resistance and mutagenesis},
journal = {Microbiology},
year = {2010},
volume = {156},
pages = {374--384},
number = {2},
month = feb,
abstract = {The SOS response is a conserved pathway that is activated under certain
stress conditions and is regulated by the repressor LexA and the
activator RecA. The food-borne pathogen Listeria monocytogenes contains
RecA and LexA homologues, but their roles in Listeria have not been
established. In this study, we identified the SOS regulon in L. monocytogenes
by comparing the transcription profiles of a wild-type strain and
a {Delta}recA mutant strain after exposure to the DNA-damaging agent
mitomycin C. In agreement with studies in other bacteria, we identified
an imperfect palindrome AATAAGAACATATGTTCGTTT as the SOS operator
sequence. The SOS regulon of L. monocytogenes consists of 29 genes
in 16 LexA-regulated operons, encoding proteins with functions in
translesion DNA synthesis and DNA repair. We furthermore identified
a role for the product of the LexA-regulated gene yneA in cell elongation
and inhibition of cell division. As anticipated, RecA of L. monocytogenes
plays a role in mutagenesis; {Delta}recA cultures showed considerably
lower rifampicin- and streptomycin-resistant fractions than the wild-type
cultures. The SOS response is activated after stress exposure as
shown by recA- and yneA-promoter reporter studies. Stress-survival
studies showed {Delta}recA mutant cells to be less resistant to heat,
H2O2 and acid exposure than wild-type cells. Our results indicate
that the SOS response of L. monocytogenes contributes to survival
upon exposure to a range of stresses, thereby likely contributing
to its persistence in the environment and in the host.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/156/2/374}
}
@ARTICLE{Veening2004,
author = {Veening, Jan-Willem and Smits, Wiep Klaas and Hamoen, Leendert W.
and Jongbloed, Jan D. H. and Kuipers, Oscar P.},
title = {Visualization of Differential Gene Expression by Improved Cyan Fluorescent
Protein and Yellow Fluorescent Protein Production in Bacillus subtilis},
journal = {Appl. Envir. Microbiol.},
year = {2004},
volume = {70},
pages = {6809--6815},
number = {11},
month = nov,
abstract = {The distinguishable cyan and yellow fluorescent proteins (CFP and
YFP) enable the simultaneous in vivo visualization of different promoter
activities. Here, we report new cloning vectors for the construction
of cfp and yfp fusions in Bacillus subtilis. By extending the N-terminal
portions of previously described CFP and YFP variants, 20- to 70-fold-improved
fluorescent-protein production was achieved. Probably, the addition
of sequences encoding the first eight amino acids of the N-terminal
part of ComGA of B. subtilis overcomes the slow translation initiation
that is provoked by the eukaryotic codon bias present in the original
cfp and yfp genes. Using these new vectors, we demonstrate that,
within an isogenic population of sporulating B. subtilis cells, expression
of the abrB and spoIIA genes is distinct in individual cells.},
url = {http://aem.asm.org/cgi/content/abstract/70/11/6809}
}
@ARTICLE{Veerdonk2011,
author = {van de Veerdonk, Frank L. and Lauwerys, Bernard and Marijnissen,
Renoud J. and Timmermans, Kim and Di Padova, Franco and Koenders,
Marije I. and Gutierrez-Roelens, Ilse and Durez, Patrick and Netea,
Mihai G. and van der Meer, Jos W. M. and van den Berg, Wim B. and
Joosten, Leo A. B.},
title = {The anti-CD20 antibody rituximab reduces the Th17 cell response},
journal = {Arthritis \& Rheumatism},
year = {2011},
volume = {63},
pages = {1507--1516},
number = {6},
abstract = {ObjectiveRituximab has been shown to be successful in the treatment
of rheumatoid arthritis (RA), and this unexpected finding indicates
that B cells have an important role in this disease. The present
study was undertaken to investigate the mechanism of action of rituximab
in RA.MethodsTwelve patients with active RA were treated with rituximab.
Disease activity was evaluated using the 28-joint Disease Activity
Score. Synovial biopsy samples obtained at baseline and 12 weeks
after treatment initiation were analyzed by microarray, quantitative
polymerase chain reaction, and immunohistochemistry. Peripheral blood
mononuclear cells (PBMCs) from healthy volunteers and from 4 patients
with X-linked agammaglobulinemia were stimulated with the Th17-inducing
stimulus Candida albicans, and the response in the presence and absence
of rituximab was examined.ResultsIn RA patients, rituximab reduced
expression of retinoic acid–related orphan receptor γt and interleukin-22
(IL-22) and numbers of Th17-positive cells in synovial tissue, and
this correlated with better clinical outcome. Rituximab did not affect
tumor necrosis factor α (TNFα), Th1 cell, or Treg cell responses.
Rituximab strongly reduced in vitro IL-17 and IL-22 production induced
by C albicans. This effect was not observed in PBMCs from patients
with X-linked agammaglobulinemia.ConclusionRituximab reduced the
local Th17 response in RA patients, whereas it did not influence
Th1 cell, Treg cell, or TNFα responses. The decreased Th17 response
was associated with reduced inflammation and better clinical outcome.
Moreover, inhibition of the Th17 response by rituximab was lost in
the absence of B cells, providing evidence that the effects of rituximab
are due to B cell depletion. These data demonstrate an unexpected
role of B cells in the development of Th17 responses, which could
possibly lead to B cell–based strategies for the treatment of Th17-related
autoimmune diseases.},
doi = {10.1002/art.30314},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.30314}
}
@ARTICLE{Veerla2009,
author = {Veerla, Srinivas and Lindgren, David and Kvist, Anders and Frigyesi,
Attila and Staaf, Johan and Persson, Helena and Liedberg, Fredrik
and Chebil, Gunilla and Gudjonsson, Sigurdur and Borg, Ã…ke and MÃ¥nsson,
Wiking and Rovira, Carlos and Höglund, Mattias},
title = {MiRNA expression in urothelial carcinomas: Important roles of miR-10a,
miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis,
and frequent homozygous losses of miR-31},
journal = {Int. J. Cancer},
year = {2009},
volume = {124},
pages = {2236--2242},
number = {9},
abstract = {Abstract 10.1002/ijc.24183.abs We analyzed 34 cases of urothelial
carcinomas by miRNA, mRNA and genomic profiling. Unsupervised hierarchical
clustering using expression information for 300 miRNAs produced 3
major clusters of tumors corresponding to Ta, T1 and T2-T3 tumors,
respectively. A subsequent SAM analysis identified 51 miRNAs that
discriminated the 3 pathological subtypes. A score based on the expression
levels of the 51 miRNAs, identified muscle invasive tumors with high
precision and sensitivity. MiRNAs showing high expression in muscle
invasive tumors included miR-222 and miR-125b and in Ta tumors miR-10a.
A miRNA signature for FGFR3 mutated cases was also identified with
miR-7 as an important member. MiR-31, located in 9p21, was found
to be homozygously deleted in 3 cases and miR-452 and miR-452* were
shown to be over expressed in node positive tumors. In addition,
these latter miRNAs were shown to be excellent prognostic markers
for death by disease as outcome. The presented data shows that pathological
subtypes of urothelial carcinoma show distinct miRNA gene expression
signatures. © 2008 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {bladder, miRNA, expression profiling, homozygous deletion, FGFR3 mutation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24183}
}
@ARTICLE{Veerla2008,
author = {Veerla, Srinivas and Panagopoulos, Ioannis and Jin, Yuesheng and
Lindgren, David and Höglund, Mattias},
title = {Promoter analysis of epigenetically controlled genes in bladder cancer},
journal = {Genes Chromosom. Cancer},
year = {2008},
volume = {47},
pages = {368--378},
number = {5},
abstract = {Abstract 10.1002/gcc.20542.abs DNA methylation is an important epigenetic
modification that regulates several genes crucial for tumor development.
To identify epigenetically regulated genes in bladder cancer, we
performed genome wide expression analyses of eight-bladder cancer
cell lines treated with the demethylating agents 5-aza-2′-cytidine
and zebularine. To identify methylated C-residues, we sequenced cloned
DNA fragments from bisulfite-treated genomic DNA. We identified a
total of 1092 genes that showed ≥2-fold altered expression in at
least one cell line; 710 showed up-regulation and 382 down-regulation.
Extensive sequencing of promoters from 25 genes in eight cell lines
showed an association between methylation pattern and expression
in 13 genes, including both CpG island and non-CpG island genes.
Overall, the methylation patterns showed a patchy appearance with
short segments showing high level of methylation separated by larger
segments with no methylation. This pattern was not associated with
MeCP2 binding sites or with evolutionarily conserved sequences. The
genes UBXD2, AQP11, and TIMP1 showed particular patchy methylation
patterns. We found several high-scoring and evolutionarily conserved
transcription factor binding sites affected by methylated C residues.
Two of the genes, FGF18 and MMP11, that were down-regulated as response
to 5-aza-2′-cytidine and zebularine treatment showed methylation
at specific sites in the untreated cells indicating an activating
result of methylation. Apart from identifying epigenetically regulated
genes, including TGFBR1, NUPR1, FGF18, TIMP1, and MMP11, that may
be of importance for bladder cancer development the presented data
also highlight the organization of the modified segments in methylated
promoters. This article contains supplementary material available
via the Internet at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
© 2008 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20542}
}
@ARTICLE{Vega2004,
author = {Vega, Francisco M. and Sevilla, Ana and Lazo, Pedro A.},
title = {p53 Stabilization and Accumulation Induced by Human Vaccinia-Related
Kinase 1},
journal = {Mol. Cell. Biol.},
year = {2004},
volume = {24},
pages = {10366--10380},
number = {23},
month = dec,
abstract = {Variations in intracellular levels of p53 regulate many cellular functions
and determine tumor susceptibility. Major mechanisms modulating p53
levels include phosphorylation and interaction of p53 with specific
ubiquitin ligases that promote its degradation. N-terminal phosphorylation
regulates the interaction of p53 with several regulatory molecules.
Vaccinia-related kinase 1 (VRK1) is the prototype of a new Ser-Thr
kinase family in the human kinome. VRK1 is located in the nucleus
outside the nucleolus. Overexpression of VRK1 increases the stability
of p53 by a posttranslational mechanism leading to its accumulation
by a mechanism independent of the Chk2 kinase. Catalytically inactive
VRK1 protein (a K179E mutant) does not induce p53 accumulation. VRK1
phosphorylates human p53 in Thr18 and disrupts p53-Mdm2 interaction
in vitro, although a significant decrease in p53 ubiquitination by
Mdm2 in vivo was not detected. VRK1 kinase does not phosphorylate
Mdm2. VRK1-mediated p53 stabilization was also detected in Mdm2-/-
cells. VRK1 also has an additive effect with MdmX or p300 to stabilize
p53, and p300 coactivation and acetylation of p53 is enhanced by
VRK1. The p53 stabilized by VRK1 is transcriptionally active. Suppression
of VRK1 expression by specific small interfering RNA provokes several
defects in proliferation, situating the protein in the regulation
of this process. VRK1 might function as a switch controlling the
proteins that interact with p53 and thus modifying its stability
and activity. We propose VRK1 as the first step in a new pathway
regulating p53 activity during cell proliferation.},
url = {http://mcb.asm.org/cgi/content/abstract/24/23/10366}
}
@ARTICLE{Vegas2010,
author = {Vegas, Carlos and Mateo, Estibaliz and González, Ángel and Jara,
Carla and Guillamón, José Manuel and Poblet, Montse and Torija, M
Jesús and Mas, Albert},
title = {Population dynamics of acetic acid bacteria during traditional wine
vinegar production},
journal = {International Journal of Food Microbiology},
year = {2010},
volume = {138},
pages = {130--136},
number = {1-2},
month = mar,
abstract = {The population dynamics of acetic acid bacteria in traditional vinegar
production was determined in two independent vinegar plants at both
the species and strain level. The effect of barrels made of four
different woods upon the population dynamics was also determined.
Acetic acid bacteria were isolated on solid media and the species
were identified by RFLP-PCR of 16S rRNA genes and confirmed by 16S
rRNA gene sequencing, while strains were typed by ERIC-PCR and (GTG)5-rep-PCR.
The most widely isolated species was Acetobacter pasteurianus, which
accounted for 100% of all the isolates during most of the acetification.
Gluconacetobacter europaeus only appeared at any notable level at
the end of the process in oak barrels from one vinegar plant. The
various A. pasteurianus strains showed a clear succession as the
concentration of acetic acid increased. In both vinegar plants the
relative dominance of different strains was modified as the concentrations
of acetic acid increased, and strain diversity tended to reduce at
the end of the process.},
issn = {0168-1605},
keywords = {Acetobacter pasteurianus, Gluconacetobacter europaeus, Oak, Cherry,
Acacia, Chestnut},
url = {http://www.sciencedirect.com/science/article/B6T7K-4Y5BM8D-3/2/32ef8d14e3858aab6cbca67b19474fc2}
}
@ARTICLE{Veidal2010,
author = {Veidal, Sanne S. and Vassiliadis, Efstathios and Barascuk, Natasha
and Zhang, Chen and Segovia-Silvestre, Toni and Klickstein, Lloyd
and Larsen, Martin R. and Qvist, Per and Christiansen, Claus and
Vainer, Ben and Karsdal, Morten A.},
title = {Matrix metalloproteinase-9-mediated type III collagen degradation
as a novel serological biochemical marker for liver fibrogenesis},
journal = {Liver International},
year = {2010},
volume = {30},
pages = {1293--1304},
number = {9},
abstract = {Abstract Background: During fibrogenesis in the liver, in which excessive
remodelling of the extracellular matrix (ECM) occurs, both the quantity
of type III collagen (CO3) and levels of matrix metalloproteinases
(MMPs), including MMP-9, increase significantly. MMPs play major
roles in ECM remodelling, via their activity in the proteolytic degradation
of extracellular macromolecules such as collagens, resulting in the
generation of specific cleavage fragments. These neo-epitopes may
be used as markers of fibrosis. Aims: The current study investigated
whether a novel enzyme-linked immunosorbent assay (ELISA) assay specifically
measuring an MMP-9-cleaved sequence of type III collagen located
at position 610 (CO3-610C) may be used as a marker of liver fibrosis.
Material and methods: Bile duct ligation (BDL) was performed in 20
rats, with sham operations performed on another 20 rats. Serum levels
of the neo-epitope CO3-610C (MMP-mediated type III collagen degradation)
were determined with an ELISA at 14 and 28 days post-surgery. Liver
fibrosis was evaluated by quantitative digital image analysis of
Sirius red-stained formalin-fixed and paraffin-embedded sections.
Western blot and densitometry were performed to confirm the CO3-610C
ELISA data. Results: CO3-610C levels in serum increased significantly
in BDL rats compared with those undergoing sham operations (% increase:
14 days=153%, P<0.0001; 28 days=134%, P=0.0014). This increase was
confirmed by Western blot and densitometry of the identified bands.
The CO3-610C levels correlated to liver fibrosis (R2=0.23 and P=0.01),
as evaluated by quantitative digital histology. Discussion and conclusion:
The data suggest that MMP-9-mediated CO3 turnover is a central event
in the pathogenesis of fibrosis, and that the neo-epitope generated
may be a novel biochemical marker.},
issn = {1478-3231},
keywords = {bile duct ligation, biomarkers, collagen, extracellular matrix, fibrosis,
liver, neo-epitope},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1478-3231.2010.02309.x}
}
@ARTICLE{Veilleux2009,
author = {Veilleux, Alain and Blouin, Karine and Rhéaume, Caroline and Daris,
Marleen and Marette, André and Tchernof, André},
title = {Glucose transporter 4 and insulin receptor substrate-1 messenger
RNA expression in omental and subcutaneous adipose tissue in women},
journal = {Metabolism},
year = {2009},
volume = {58},
pages = {624--631},
number = {5},
month = may,
abstract = {Insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4)
expression may provide an indirect reflection of the capacity of
adipocytes to respond to insulin stimulation. We examined messenger
RNA (mRNA) expression of these genes in omental and subcutaneous
adipose tissue of women. Paired omental and subcutaneous adipose
tissue samples were obtained from 36 women (age, 47 ± 5 years; body
mass index, 28.0 ± 5.4 kg/m2) undergoing gynecologic surgeries. Total
adiposity and visceral adiposity were assessed by dual-energy x-ray
absorptiometry and computed tomography. The GLUT4 and IRS-1 mRNA
expression levels were both significantly higher in subcutaneous
compared with omental adipose tissue. A negative correlation was
observed between body fat percentage and subcutaneous adipose tissue
GLUT4 (r = -0.39, P < .05) and IRS-1 (r = -0.30, P < .08) mRNA abundance.
However, in omental fat, only GLUT4 mRNA was inversely associated
with body fat percentage (r = -0.53, P < .001). Moreover, the homeostasis
model assessment of insulin resistance index was associated with
mRNA expression of subcutaneous GLUT4 (r = -0.56, P < .001), subcutaneous
IRS-1 (r = -0.51, P < .01), and omental GLUT4 (r = -0.54, P < .001),
but not omental IRS-1. Interestingly, plasma adiponectin was only
associated with subcutaneous GLUT4 (r = 0.48, P < .01) and IRS-1
(r = 0.48, P < .05) mRNA expression. The GLUT4 protein, unlike mRNA
expression, was higher in omental than in subcutaneous adipose tissue.
However, abdominal obesity-related differences in protein or mRNA
expression were similar. Omental IRS-1 expression was low and unaffected
by visceral obesity. In contrast, omental and subcutaneous GLUT4
as well as subcutaneous IRS-1 were reduced in visceral obesity. This
divergent pattern of expression may reflect a lower capacity of omental
adipose tissue to respond to insulin stimulation at all adiposity
levels.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/B6WN4-4W34W73-C/2/74f09e78f45683ff52954126a0aa43c4}
}
@ARTICLE{Veilleux2010,
author = {Veilleux, Alain and Laberge, Philippe Y. and Morency, Jacques and
Noël, Suzanne and Luu-The, Van and Tchernof, André},
title = {Expression of genes related to glucocorticoid action in human subcutaneous
and omental adipose tissue},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2010},
volume = {122},
pages = {28--34},
number = {1-3},
month = oct,
abstract = {Adipose tissue glucocorticoid action relies on local enzymatic interconversion
and glucocorticoid receptor (GR) availability. 11[beta]-Hydroxysteroid
dehydrogenase type 1 (11[beta]-HSD1), 2 (11[beta]-HSD2) and hexose-6-phosphate
dehydrogenase (H6PDH) are likely involved in glucocorticoid activation/inactivation
within adipose tissue. We examined adipose tissue mRNA expression
of genes related to glucocorticoid action and their association with
total and visceral adiposity. Messenger RNA was measured in paired
subcutaneous and omental fat samples obtained from 56 women (age:
47.3 ± 4.8 years, BMI: 27.1 ± 5.2 kg/m2) undergoing gynaecological
surgery. Expression levels of 11[beta]-HSD2, H6PDH and GR[alpha]
were higher in omental adipose tissue while 11[beta]-HSD1 expression
was similar between fat compartments. Subcutaneous and omental 11[beta]-HSD1
mRNA abundances were positively associated with total and visceral
adiposity whereas omental H6PDH mRNA abundance was negatively associated
with these measures. Only omental 11[beta]-HSD1 mRNA expression remained
significantly associated with visceral adipose tissue area following
statistical adjustment for fat mass, age and menopausal status. Omental
11[beta]-HSD1 mRNA expression explained 19.1% of the variance in
visceral adipose tissue area. Omental fat tissue 11[beta]-HSD-1 protein
and cortisol levels were higher in visceral obese women, supporting
findings obtained with 11[beta]-HSD-1 mRNA. These results suggest
that among the transcripts examined only omental 11[beta]-HSD1 is
independently associated with visceral obesity in women.},
booktitle = {Steroids in obesity and diabetes},
issn = {0960-0760},
keywords = {11[beta]-HSD1, 11[beta]-HSD2, GR[alpha], H6PDH, Adipose tissue, Body
fat distribution},
url = {http://www.sciencedirect.com/science/article/B6T8X-4YHNYVH-2/2/0919c05f3b638dfde27ccca447536878}
}
@ARTICLE{Veilleux2009a,
author = {Veilleux, Alain and Rheaume, Caroline and Daris, Marleen and Luu-The,
Van and Tchernof, Andre},
title = {Omental Adipose Tissue Type 1 11{beta}-Hydroxysteroid Dehydrogenase
Oxoreductase Activity, Body Fat Distribution, and Metabolic Alterations
in Women},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {3550--3557},
number = {9},
month = sep,
abstract = {Context: Modulation of adipose tissue exposure to active glucocorticoids
by type 1 11{beta}-hydroxysteroid dehydrogenase (11{beta}-HSD1) is
involved in abdominal obesity of rodent models, but only a few studies
have related 11{beta}-HSD1 oxoreductase activity to fat distribution
in humans. Objective: The objective of the study was to examine the
link between 11{beta}-HSD1 oxoreductase activity, fat distribution
patterns, and the metabolic profile in women. Methods: Omental (OM)
and sc adipose tissue samples were obtained from 36 lean to obese
women (aged 47.2 {+/-} 5.3 yr; body mass index 29.1 {+/-} 5.2 kg/m2)
undergoing gynecological surgery. Measures of body composition, fat
distribution, blood lipids, and insulin sensitivity were obtained.
11{beta}-HSD1 oxoreductase activity was measured over a 24-h period
by the reduction of [14C]cortisone in adipose tissue homogenates.
Results: 11{beta}-HSD1 oxoreductase activity was higher in OM compared
with sc adipose tissue (9.6 {+/-} 4.9 vs. 7.9 {+/-} 4.2 pmol/mg {middle
dot} h, P < 0.01). OM 11{beta}-HSD1 oxoreductase activity was positively
associated with OM adipocyte size (r = 0.67, P < 0.0001) and visceral
adipose tissue area (r = 0.57, P < 0.0003). A positive correlation
was also observed between the OM/sc 11{beta}-HSD1 oxoreductase activity
ratio and the OM/sc adipocyte size ratio (r = 0.37, P < 0.05) as
well as the visceral/sc adipose tissue area ratio (r = 0.36, P <
0.05). Women in the highest tertile of OM 11{beta}-HSD1 oxoreductase
activity had larger OM adipocytes, increased OM lipolysis, increased
lipoprotein lipase activity, decreased high-density lipoprotein cholesterol,
decreased adiponectin levels, and an increased homeostasis model
assessment of insulin resistance index compared with women in the
lower tertile (P < 0.05). Conclusions: These results suggest that
a relatively higher 11{beta}-HSD1 activity in OM vs. sc adipose tissue
is associated with preferential visceral fat accumulation and concomitant
metabolic alterations.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/9/3550}
}
@ARTICLE{Veitch2010,
author = {Veitch, Nicola and Johnson, Paul and Trivedi, Urmi and Terry, Sandra
and Wildridge, David and MacLeod, Annette},
title = {Digital gene expression analysis of two life cycle stages of the
human-infective parasite, Trypanosoma brucei gambiense reveals differentially
expressed clusters of co-regulated genes},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {124},
number = {1},
abstract = {BACKGROUND:The evolutionarily ancient parasite, Trypanosoma brucei,
is unusual in that the majority of its genes are regulated post-transcriptionally,
leading to the suggestion that transcript abundance of most genes
does not vary significantly between different life cycle stages despite
the fact that the parasite undergoes substantial cellular remodelling
and metabolic changes throughout its complex life cycle. To investigate
this in the clinically relevant sub-species, Trypanosoma brucei gambiense,
which is the causative agent of the fatal human disease African sleeping
sickness, we have compared the transcriptome of two different life
cycle stages, the potentially human-infective bloodstream forms with
the non-human-infective procyclic stage using digital gene expression
(DGE) analysis.RESULTS:Over eleven million unique tags were generated,
producing expression data for 7360 genes, covering 81% of the genes
in the genome. Compared to microarray analysis of the related T.
b. brucei parasite, approximately 10 times more genes with a 2.5-fold
change in expression levels were detected. The transcriptome analysis
revealed the existence of several differentially expressed gene clusters
within the genome, indicating that contiguous genes, presumably from
the same polycistronic unit, are co-regulated either at the level
of transcription or transcript stability.CONCLUSIONS:DGE analysis
is extremely sensitive for detecting gene expression differences,
revealing firstly that a far greater number of genes are stage-regulated
than had previously been identified and secondly and more importantly,
this analysis has revealed the existence of several differentially
expressed clusters of genes present on what appears to be the same
polycistronic units, a phenomenon which had not previously been observed
in microarray studies. These differentially regulated clusters of
genes are in addition to the previously identified RNA polymerase
I polycistronic units of variant surface glycoproteins and procyclin
expression sites, which encode the major surface proteins of the
parasite. This raises a number of questions regarding the function
and regulation of the gene clusters that clearly warrant further
study.},
doi = {10.1186/1471-2164-11-124},
issn = {1471-2164},
pubmedid = {20175885},
url = {http://www.biomedcentral.com/1471-2164/11/124}
}
@ARTICLE{Velada2011,
author = {I. Velada and F. Capela-Silva and F. Reis and E. Pires and C. Egas
and P. Rodrigues-Santos and M.T. Barros},
title = {Expression of Genes Encoding Extracellular Matrix Macromolecules
and Metalloproteinases in Avian Tibial Dyschondroplasia},
journal = {Journal of Comparative Pathology},
year = {2011},
volume = {145},
pages = {174 - 186},
number = {2–3},
abstract = {Summary Avian tibial dyschondroplasia (TD) is a skeletal disease characterized
by disruption of endochondral bone formation. The aim of this study
was to determine the expression of extracellular matrix (ECM) macromolecules
and ECM-degrading enzymes [matrix metalloproteinases (MMPs)] in the
growth plates of normal and TD-affected 3-week-old broiler chicks
(Cobb strain). Protein levels were analyzed by immunoblotting and
gelatin zymography and gene expression by polymerase chain reaction.
Expression of genes encoding the ECM macromolecules (collagen types
II, IX, X and XI; and aggrecan) was not altered in dyschondroplasia;
however, there was down-regulation of genes encoding MMP-9, MMP-13,
MMP-10 and MMP-11 in addition to reduced amounts of MMP-2 and MMP-13
proteins. In contrast, there was up-regulation of genes encoding
MMP-7 and the vascular endothelial growth factor. These findings
suggest that the accumulation of cartilage associated with the disease
may be the result of decreased proteolysis due to the down-regulation
of MMPs and not to an increased production of ECM macromolecules.},
doi = {10.1016/j.jcpa.2010.12.008},
issn = {0021-9975},
keywords = {extracellular matrix},
url = {http://www.sciencedirect.com/science/article/pii/S002199751000366X}
}
@ARTICLE{Velarde2009,
author = {Velarde, Michael C. and Aghajanova, Lusine and Nezhat, Camran R.
and Giudice, Linda C.},
title = {Increased Mitogen-Activated Protein Kinase Kinase/Extracellularly
Regulated Kinase Activity in Human Endometrial Stromal Fibroblasts
of Women with Endometriosis Reduces 3',5'-Cyclic Adenosine 5'-Monophosphate
Inhibition of Cyclin D1},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {4701--4712},
number = {10},
month = oct,
abstract = {Endometriosis is characterized by endometrial tissue growth outside
the uterus, due primarily to survival, proliferation, and neoangiogenesis
of eutopic endometrial cells and fragments refluxed into the peritoneal
cavity during menses. Although various signaling molecules, including
cAMP, regulate endometrial proliferation, survival, and embryonic
receptivity in endometrium of women without endometriosis, the exact
molecular signaling pathways in endometrium of women with disease
remain unclear. Given the persistence of a proliferative profile
and differential expression of genes associated with the MAPK signaling
cascade in early secretory endometrium of women with endometriosis,
we hypothesized that ERK1/2 activity influences cAMP regulation of
the cell cycle. Here, we demonstrate that 8-Br-cAMP inhibits bromodeoxyuridine
incorporation and cyclin D1 (CCND1) expression in cultured human
endometrial stromal fibroblasts (hESF) from women without but not
with endometriosis. Incubation with serum-containing or serum-free
medium resulted in higher phospho-ERK1/2 levels in hESF of women
with vs. without disease, independent of 8-Br-cAMP treatment. The
MAPK kinase-1/2 inhibitor, U0126, fully restored cAMP down-regulation
of CCND1, but not cAMP up-regulation of IGFBP1, in hESF of women
with vs. without endometriosis. Immunohistochemistry demonstrated
the highest phospho-ERK1/2 in the late-secretory epithelial and stromal
cells in women without disease, in contrast to intense immunostaining
in early-secretory epithelial and stromal cells in those with disease.
These findings suggest that increased activation of ERK1/2 in endometrial
cells from women with endometriosis may be responsible for persistent
proliferative changes in secretory-phase endometrium.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/10/4701}
}
@ARTICLE{Velarde2006,
author = {Velarde, Michael C. and Iruthayanathan, Mary and Eason, Renea R.
and Zhang, Daying and Simmen, Frank A. and Simmen, Rosalia C. M.},
title = {Progesterone Receptor Transactivation of the Secretory Leukocyte
Protease Inhibitor Gene in Ishikawa Endometrial Epithelial Cells
Involves Recruitment of Kruppel-Like Factor 9/Basic Transcription
Element Binding Protein-1},
journal = {Endocrinology},
year = {2006},
volume = {147},
pages = {1969--1978},
number = {4},
month = apr,
abstract = {Progesterone receptor (PR), a ligand-inducible transcription factor,
mediates the physiological actions of progesterone (P) through two
distinct isoforms, PR-A and PR-B, and numerous nuclear coregulators.
We previously demonstrated that basic transcription element binding
protein-1 (BTEB1), a transcription factor of the Kruppel-like family,
is a functional PR-interacting protein, based on the subfertility
phenotype and reduced P sensitivity of uterine PR target genes, on
BTEB1 null mutation. Here we examined the role of BTEB1 in PR-mediated
signaling in endometrial epithelial cells using Ishikawa human endocarcinoma
cells and the P-responsive secretory leukocyte protease inhibitor
(SLPI) gene. Treatment of Ishikawa cells with P for 24 h increased
SLPI and BTEB1 transcript levels without similar effects on PR expression.
P induction was abolished by the PR antagonist RU486, whereas knockdown
of BTEB1 with short interfering RNA reduced P-responsive BTEB1 but
not SLPI expression to basal levels. Forced expression of BTEB1,
either by stable or transient transfections of BTEB1 expression constructs
in endometrial carcinoma cells, enhanced SLPI promoter activity.
Chromatin immunoprecipitation with anti-BTEB1 antibody demonstrated
BTEB1 recruitment to the proximal GC-rich containing SLPI promoter
region (-97 to -86) in human endometrial carcinoma (Hec1A) cells
overexpressing BTEB1. In Ishikawa cells, recruitment of BTEB1 to
the proximal, GC-rich region and the distal, progesterone-responsive
element-like containing region (-635 to -514) was P dependent and
was accompanied by corecruitment of PR and the PR coactivator cAMP-response
element binding protein-binding protein. PR-B, rather than PR-A isoform,
preferentially associated with BTEB1 in the GC-rich region, whereas
both PR isoforms were recruited to the progesterone-responsive element-like
site along with BTEB1. Our findings define a novel pathway for BTEB1/PR
cross-talk to facilitate P-dependent gene transcription in endometrial
epithelial cells.},
url = {http://endo.endojournals.org/cgi/content/abstract/147/4/1969}
}
@ARTICLE{Velarde2005,
author = {Velarde, M C and Parisek, S I and Eason, R R and Simmen, F A and
Simmen, R C M},
title = {The secretory leukocyte protease inhibitor gene is a target of epidermal
growth factor receptor action in endometrial epithelial cells},
journal = {J. Endocrinol.},
year = {2005},
volume = {184},
pages = {141--151},
number = {1},
month = jan,
abstract = {The over-expression of epidermal growth factor receptor (EGFR) and
its ligands, epidermal growth factor (EGF) and transforming growth
factor-{alpha}, is a common feature of epithelial carcinomas and
correlates with neoplastic progression. Secretory leukocyte protease
inhibitor (SLPI), a member of the Kazal superfamily of serine anti-proteases,
induces proliferation and promotes malignancy of epithelial cells
and is expressed at high levels in multiple tumor types. In the present
study, we have demonstrated that EGF increases SLPI expression in
the human endometrial epithelial cell line Ishikawa in a dose- and
time-dependent manner. We have shown that this effect of EGF occurs,
in part, at the level of the SLPI promoter and involves the MAP kinase
signaling pathway. We have further shown that EGF promotion of cell
proliferation, but not induction of cyclin D1 gene expression, involves
SLPI. Our results suggest that the regulation of SLPI expression
by EGFR ligand(s) may represent a feed-forward' mechanism by which
the enhanced proliferative and migratory properties of EGFR over-expressing
cancer cells are sustained. Increased SLPI expression is likely an
important component of altered EGFR signaling in human tumors and
may have significant therapeutic implications in cancer progression.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/184/1/141}
}
@ARTICLE{Velarde2007,
author = {Velarde, Michael C. and Zeng, Zhaoyang and McQuown, Jennelle R. and
Simmen, Frank A. and Simmen, Rosalia C. M.},
title = {Kruppel-Like Factor 9 Is a Negative Regulator of Ligand-Dependent
Estrogen Receptor {alpha} Signaling in Ishikawa Endometrial Adenocarcinoma
Cells},
journal = {Mol. Endocrinol.},
year = {2007},
volume = {21},
pages = {2988--3001},
number = {12},
month = dec,
abstract = {Estrogen and progesterone, acting through their respective receptors
and other nuclear proteins, exhibit opposing activities in target
cells. We previously reported that Kruppel-like factor 9 (KLF9) cooperates
with progesterone receptor (PR) to facilitate P-dependent gene transcription
in uterine epithelial cells. Here we evaluated whether KLF9 may further
support PR function by directly opposing estrogen receptor (ER) signaling.
Using human Ishikawa endometrial epithelial cells, we showed that
17{beta}-estradiol (E2)-dependent down-regulation of ER{alpha} expression
was reversed by a small interfering RNA to KLF9. Transcription assays
with the E2-sensitive 4x estrogen-responsive element-thymidine kinase-promoter-luciferase
reporter gene demonstrated inhibition of ligand-dependent ER{alpha}
transactivation with ectopic KLF9 expression. E2 induced PR-A/B and
PR-B isoform expression in the absence of effects on KLF9 levels.
Addition of KLF9 small interfering RNA augmented E2 induction of
PR-A/B while abrogating that of PR-B, indicating selective E2-mediated
inhibition of PR-A by KLF9. Chromatin immunoprecipitation of the
ER{alpha} minimal promoter demonstrated KLF9 promotion of E2-dependent
ER{alpha} association to a region containing functional GC-rich motifs.
KLF9 inhibited the recruitment of the ER{alpha} coactivator specificity
protein 1 (Sp1) to the PR proximal promoter region containing a half-estrogen
responsive element and GC-rich sites, but had no effect on Sp1 association
to the PR distal promoter region containing GC-rich sequences. In
vivo association of KLF9 and Sp1, but not of ER{alpha} with KLF9
or Sp1, was observed in control and E2-treated cells. Our data identify
KLF9 as a transcriptional repressor of ER{alpha} signaling and suggest
that it may function at the node of PR and ER genomic pathways to
influence cell proliferation.},
url = {http://mend.endojournals.org/cgi/content/abstract/21/12/2988}
}
@ARTICLE{Velazquez-Arellano2011,
author = {Velazquez-Arellano, Antonio and Ortega-Cuellar, Daniel and Hernandez-Mendoza,
Armando and Moreno-Arriola, Elizabeth},
title = {A heuristic model for paradoxical effects of biotin starvation on
carbon metabolism genes in the presence of abundant glucose},
journal = {Molecular Genetics and Metabolism},
year = {2011},
volume = {102},
pages = {69--77},
number = {1},
month = jan,
abstract = {We recently showed that in biotin starvation in yeast Saccharomyces
cerevisiae, nematode Caenorhabditis elegans and rat Rattus norvegicus,
despite abundant glucose provision, the expression of genes for glucose
utilization and lipogenesis were lowered, and for fatty acid [beta]-oxidation
and gluconeogenesis were raised, and glycolytic/fermentative flow
was reduced. This work explored the mechanisms of these results.
We show that they are associated with ATP deficit and activation
of the energy stress sensor AMP kinase (AMPK; Snf1 in yeast). Analysis
of microarray results revealed extensive changes of transcripts for
signal transduction pathways and transcription factors AMPK, SREBP-1c,
ChREBP, NAMPT, PGC-1[alpha], mTORC1 in rat, and their homologs in
worm. In yeast the altered factor transcripts were Adr1, Cat8, Sip4,
Mig1, HXK2, and Rgt1. The insulin pathway was negatively enriched
(in rat and worm), whereas the adiponectins and JAK/STAT pathways
were increased (present only in the rat; they activate AMPK). Together,
all these changes explain the effects of biotin starvation on glucose
utilization, energy status and carbon metabolism gene expression
in a coherent manner across three phylogenetically distant eukaryotes
and may have clinical significance in humans, since the effects are
reminiscent of insulin resistance. We propose a general model for
integrating these results in regulatory circuitries, according to
the biology of each species, based on impaired anaplerosis due to
pyruvate carboxylase deficiency, that have a basic underlying logic.
In a preliminary test in yeast, aspartate corrects all the alterations
produced by biotin starvation.},
issn = {1096-7192},
keywords = {Biotin, Yeast, Saccharomyces cerevisiae, Nematode, Caenorhabditis
elegans, Rat, Rattus norvegicus, Glucose, Fatty acid, [beta]-oxidation,
Gluconeogenesis, Glycolysis, Fermentation, ATP, AMPK, Snf1, Microarrays,
SREBP-1c, ChREBP, NAMPT, PGC-1[alpha], mTORC1, Adr1, Cat8, Sip4,
Mig1, HXK2, Rgt1, Insulin pathway, Adiponectins, JAK/STAT pathway,
Carbon metabolism, Insulin resistance, Anaplerosis, Pyruvate carboxylase
deficiency, Aspartate},
url = {http://www.sciencedirect.com/science/article/pii/S1096719210003203}
}
@ARTICLE{Velde2007,
author = {te Velde, Anje A. and de Kort, Floor and Sterrenburg, Ellen and Pronk,
Inge and ten Kate, Fiebo J.W. and Hommes, Daniel W. and van Deventer,
Sander J.H.},
title = {Comparative analysis of colonic gene expression of three experimental
colitis models mimicking inflammatory bowel disease},
journal = {Inflamm Bowel Dis},
year = {2007},
volume = {13},
pages = {325--330},
number = {3},
abstract = {Abstract 10.1002/ibd.20079.abs Background: Mouse models of inflammatory
bowel diseases (IBD) are used to unravel the pathophysiology of IBD
and to study new treatment modalities, but their relationship to
Crohn's disease (CD) or ulcerative colitis (UC) is speculative. Methods:
Using Agilent mouse TOX oligonucleotide microarrays, we analyzed
colonic gene expression profiles in three widely used models of experimental
colitis. In 2 of the models (TNBS and DSS-induced colitis), exogenous
agents induce the colitis. In the third model the colitis is induced
after transfer of a T-cell population (CD4+CD45RBhigh T cells) that
lacks regulatory cells into an immunodeficient host. Results: Compared
with control mice, in DSS, TNBS, and the CD45RB transfer colitis
mice, 387, 21, and 582 genes were more than 2-fold upregulated in
the intestinal mucosa. Analyses of exclusively shared gene expression
profiles between the different models revealed that DSS/transfer
colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and
TNBS/transfer colitis 1. Seven genes were upregulated in all three
models. The CD45RB transfer model expression profile included the
most genes that are known to be upregulated in IBD. Of 32 genes that
are known to change transcriptional activity in IBD (TNF, IFN-γ,
Ltβ, IL-6, IL-16, IL-18R1, IL-22, CCR2, 7, CCL2, 3, 4, 5, 7, 11,
17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3γ, and Pap,
S-100a8, S-100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS,
15/32 are upregulated or downregulated in DSS and 30/32 are upregulated
or downregulated in the CD45RB transfer colitis. Conclusion: The
pattern of gene expression in the CD45RB transfer model most closely
reflects altered gene expression in IBD. (Inflamm Bowel Dis 2007)},
issn = {1536-4844},
keywords = {IBD, experimental colitis, gene expression, TNBS, DSS, CD45RB transfer},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.20079}
}
@ARTICLE{Veldman2007,
author = {Veldman, Matthew B. and Bemben, Michael A. and Thompson, Robert C.
and Goldman, Daniel},
title = {Gene expression analysis of zebrafish retinal ganglion cells during
optic nerve regeneration identifies KLF6a and KLF7a as important
regulators of axon regeneration},
journal = {Developmental Biology},
year = {2007},
volume = {312},
pages = {596--612},
number = {2},
month = dec,
abstract = {Unlike mammals, teleost fish are able to mount an efficient and robust
regenerative response following optic nerve injury. Although it is
clear that changes in gene expression accompany axonal regeneration,
the extent of this genomic response is not known. To identify genes
involved in successful nerve regeneration, we analyzed gene expression
in zebrafish retinal ganglion cells (RGCs) regenerating their axons
following optic nerve injury. Microarray analysis of RNA isolated
by laser capture microdissection from uninjured and 3-day post-optic
nerve injured RGCs identified 347 up-regulated and 29 down-regulated
genes. Quantitative RT-PCR and in situ hybridization were used to
verify the change in expression of 19 genes in this set. Gene ontological
analysis of the data set suggests regenerating neurons up-regulate
genes associated with RGC development. However, not all regeneration-associated
genes are expressed in differentiating RGCs indicating the regeneration
is not simply a recapitulation of development. Knockdown of six highly
induced regeneration-associated genes identified two, KLF6a and KLF7a,
that together were necessary for robust RGC axon re-growth. These
results implicate KLF6a and KLF7a as important mediators of optic
nerve regeneration and suggest that not all induced genes are essential
to mount a regenerative response.},
issn = {0012-1606},
keywords = {Optic nerve, Regeneration, Retina, Gene expression, Microarray, Zebrafish,
KLF6, KLF7, SOCS3, Sox11, Retinal ganglion cell},
url = {http://www.sciencedirect.com/science/article/B6WDG-4PR3GDB-2/2/395a301adbbcdb82c5e58c67b7d808be}
}
@ARTICLE{Velez2007,
author = {Velez, Monica Perea and Verhoeven, Tine L. A. and Draing, Christian
and Von Aulock, Sonja and Pfitzenmaier, Markus and Geyer, Armin and
Lambrichts, Ivo and Grangette, Corinne and Pot, Bruno and Vanderleyden,
Jos and De Keersmaecker, Sigrid C. J.},
title = {Functional Analysis of D-Alanylation of Lipoteichoic Acid in the
Probiotic Strain Lactobacillus rhamnosus GG},
journal = {Appl. Envir. Microbiol.},
year = {2007},
volume = {73},
pages = {3595--3604},
number = {11},
month = jun,
abstract = {Lipoteichoic acid (LTA) is a macroamphiphile molecule which performs
several functions in gram-positive bacteria, such as maintenance
of cell wall homeostasis. D-Alanylation of LTA requires the proteins
encoded by the dlt operon, and this process is directly related to
the charge properties of this polymer strongly contributing to its
function. The insertional inactivation of dltD of the probiotic strain
Lactobacillus rhamnosus GG (ATCC 53103) resulted in the complete
absence of D-alanyl esters in the LTA as confirmed by nuclear magnetic
resonance analysis. This was reflected in modifications of the bacterial
cell surface properties. The dltD strain showed 2.4-fold-increased
cell length, a low survival capacity in response to gastric juice
challenge, an increased sensitivity to human beta-defensin-2, an
increased rate of autolysis, an increased capacity to initiate growth
in the presence of an anionic detergent, and a decreased capacity
to initiate growth in the presence of cationic peptides compared
to wild-type results. However, in vitro experiments revealed no major
differences for adhesion to human intestinal epithelial cells, biofilm
formation, and immunomodulation. These properties are considered
to be important for probiotics. The role of the dlt operon in lactobacilli
is discussed in view of these results.},
url = {http://aem.asm.org/cgi/content/abstract/73/11/3595}
}
@ARTICLE{Veljkovic2009,
author = {Veljkovic, D. Kika and Rivard, Georges E. and Diamandis, Maria and
Blavignac, Jessica and Cramer-Borde, Elisabeth M. and Hayward, Catherine
P. M.},
title = {Increased expression of urokinase plasminogen activator in Quebec
platelet disorder is linked to megakaryocyte differentiation},
journal = {Blood},
year = {2009},
volume = {113},
pages = {1535--1542},
number = {7},
month = feb,
abstract = {Quebec platelet disorder (QPD) is an inherited bleeding disorder associated
with increased urokinase plasminogen activator (uPA) in platelets
but not in plasma, intraplatelet plasmin generation, and {alpha}-granule
protein degradation. These abnormalities led us to investigate uPA
expression by QPD CD34+ progenitors, cultured megakaryocytes, and
platelets, and whether uPA was stored in QPD {alpha}-granules. Although
QPD CD34+ progenitors expressed normal amounts of uPA, their differentiation
into megakaryocytes abnormally increased expression of the uPA gene
but not the flanking genes for vinculin or calcium/calmodulin-dependent
protein kinase II{gamma} on chromosome 10. The increased uPA production
by cultured QPD megakaryocytes mirrored their production of {alpha}-granule
proteins, which was normal. uPA was localized to QPD {alpha}-granules
and it showed extensive colocalization with {alpha}-granule proteins
in both cultured QPD megakaryocytes and platelets, and with plasminogen
in QPD platelets. In QPD megakaryocytes, cultured without or with
plasma as a source of plasminogen, {alpha}-granule proteins were
stored undegraded and this was associated with much less uPA-plasminogen
colocalization than in QPD platelets. Our studies indicate that the
overexpression of uPA in QPD emerges with megakaryocyte differentiation,
without altering the expression of flanking genes, and that uPA is
costored with {alpha}-granule proteins prior to their proteolysis
in QPD.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/7/1535}
}
@ARTICLE{Velkov2010,
author = {Velkov, Tony and Rimmer, Kieran A. and Headey, Stephen J.},
title = {Ligand-enhanced expression and in-cell assay of human peroxisome
proliferator-activated receptor alpha ligand binding domain},
journal = {Protein Expression and Purification},
year = {2010},
volume = {70},
pages = {260--269},
number = {2},
month = apr,
abstract = {A human peroxisome proliferator-activated receptor alpha ligand binding
domain (PPAR[alpha]LBD)-maltose binding protein fusion construct
was expressed in Escherichia coli. A codon optimized DNA sequence
encoding human PPAR[alpha]LBD (aa196-468) was synthesized and ligated
into the pDEST17 E. coli expression vector downstream of a MBP solubility
fusion tag and an intermittent TEV protease cleavage site. Following
auto-induction at 28 °C, PPAR[alpha]LBD protein was purified to electrophoretic
homogeneity by a nickel affinity chromatographic step, on-column
TEV protease cleavage followed by Sephacryl S200 size exclusion chromatography.
The recombinant protein displayed cross-reactivity with goat anti-(human
PPAR[alpha]) polyclonal antibody and was identified as human PPAR[alpha]
by trypic peptide mass finger-printing. The addition of a PPAR[alpha]
specific ligand (fenofibric acid, GW7647 or GW590735) to the growth
media significantly stabilized the PPAR[alpha]LBD structure and enhanced
the expression of soluble protein. In-cell ligand binding was examined
by monitoring the enhancement of PPAR[alpha]LBD expression as a function
of the concentration of ligand in the growth media. The efficient
expression and in-cell assay of the reported PPAR[alpha]LBD construct
make it amenable to high through-put screening assays in drug discovery
programs.},
issn = {1046-5928},
keywords = {Peroxisome proliferator-activated receptor alpha ligand binding domain,
Nuclear hormone receptor, Ligand-enhanced protein expression},
url = {http://www.sciencedirect.com/science/article/B6WPJ-4X9FGSV-1/2/984ac0be163783b6e55dd7fed30561b7}
}
@ARTICLE{Vellanki2010,
author = {Vellanki, Ravi N. and Zhang, Liling and Guney, Michelle A. and Rocheleau,
Jonathan V. and Gannon, Maureen and Volchuk, Allen},
title = {OASIS/CREB3L1 Induces Expression of Genes Involved in Extracellular
Matrix Production But Not Classical Endoplasmic Reticulum Stress
Response Genes in Pancreatic {beta}-Cells},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {4146--4157},
number = {9},
month = sep,
abstract = {Old astrocyte specifically induced substance (OASIS) has previously
been shown to be a putative endoplasmic reticulum (ER) stress sensor
in astrocytes with a mechanism of activation that is similar to ATF6.
In this study we investigated the expression and activation of endogenous
and overexpressed OASIS in pancreatic {beta}-cells. OASIS mRNA expression
was detected in pancreatic {beta}-cell lines and rodent islets, and
the expression level was up-regulated by ER stress-inducing compounds.
Endogenous OASIS protein, however, is expressed at low levels in
pancreatic {beta}-cell lines and rodent islets, possibly due to abundant
levels of the micro-RNA miR-140 present in these cells. In contrast,
expression of both full-length and cleaved (active) OASIS was readily
detectable in the developing mouse pancreas (embryonic d 15.5). Microarray
analysis after expression of an active nuclear-localized version
of OASIS in an inducible INS-1 {beta}-cell line resulted in the up-regulation
of many genes implicated in extracellular matrix production and protein
transport but not classical ER stress response genes. Consistent
with this, expression of active OASIS failed to induce glucose-regulated
protein 78 kDa promoter activity in pancreatic {beta}-cells. These
results suggest that the repertoire of genes induced by OASIS is
cell type-dependent and that the OASIS protein may have a role in
pancreas development.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/9/4146}
}
@ARTICLE{Vellosillo2007,
author = {Vellosillo, Tamara and Martinez, Marta and Lopez, Miguel Angel and
Vicente, Jorge and Cascon, Tomas and Dolan, Liam and Hamberg, Mats
and Castresana, Carmen},
title = {Oxylipins Produced by the 9-Lipoxygenase Pathway in Arabidopsis Regulate
Lateral Root Development and Defense Responses through a Specific
Signaling Cascade},
journal = {PLANT CELL},
year = {2007},
volume = {19},
pages = {831--846},
number = {3},
month = mar,
abstract = {Arabidopsis thaliana seedling growth with pure oxylipins resulted
in root waving, loss of root apical dominance, and decreased root
elongation. 9-Hydroxyoctadecatrienoic acid (9-HOT) was a potent inducer
of root waving. Studies with noxy2 (for nonresponding to oxylipins2),
a new 9-HOT-insensitive mutant, and coronatine insensitive1-1 (jasmonate-insensitive)
revealed at least three signaling cascades mediating the oxylipin
actions. Treatment with 9-HOT resulted in a reduction in lateral
roots and an increase in stage V primordia. Roots showed strong 9-lipoxygenase
(9-LOX) activity, and root primordia expressed 9-LOX genes. These
results, along with findings that noxy2 and mutants with defective
9-LOX activity showed increased numbers of lateral roots, suggest
that 9-HOT, or a closely related 9-LOX product, is an endogenous
modulator of lateral root formation. Histochemical and molecular
analyses revealed that 9-HOT activated events common to development
and defense responses. A subset of 9-HOT-responding root genes was
also induced in leaves after 9-HOT treatment or pathogen inoculation.
The results that noxy2 displayed altered root development, enhanced
susceptibility to Pseudomonas, and reduced the activation of 9-HOT-responding
genes are consistent with mechanistic links among these processes.
The nature of the changes detected suggests that oxylipins from the
9-LOX pathway function in cell wall modifications required for lateral
root development and pathogen arrest.},
url = {http://www.plantcell.org/cgi/content/abstract/19/3/831}
}
@ARTICLE{Velten2004,
author = {Velten, Florian W. and Duperrier, Karine and Bohlender, Johannes
and Metharom, Patraporn and Goerdt, Sergij},
title = {A gene signature of inhibitory MHC receptors identifies a BDCA3+
subset of IL-10-induced dendritic cells with reduced allostimulatory
capacity in vitro},
journal = {Eur. J. Immunol.},
year = {2004},
volume = {34},
pages = {2800--2811},
number = {10},
abstract = {Abstract 10.1002/eji.200324732.abs Dendritic cells (DC) are crucial
gatekeepers in regulating immunity. Whereas mature immunostimulatory
myeloid DC (DCims) potently promote immune responses, IL-10-induced
myeloid DC (DC-IL-10) counteract T cell activation. To elucidate
the molecular repertoire by which DC-IL-10 secure reduced T cell
activation, comparative gene expression profiling was done using
Affymetrix U133A microarrays. Among the genes overexpressed in DC-IL-10,
eight immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing
inhibitory molecules (ILT2, ILT3, ILT4, ILT5, DCIR, PILRA, FcγRIIB,
SLAM) were found. Phenotypic analysis of DC-IL-10 defined an ILThigh
DC subset further characterized by expression of CD14, TLR2, DC-SIGN,
and CD123 and the lack of lymphocyte, monocyte/macrophage, and plasmacytoid
DC markers such as CD3, CD8, and CD68. A unique feature of the ILThigh
DC subset was expression of the novel DC marker BDCA3, which was
not detected on monocytes, immature DC, DCims, or ILTlow DC-IL-10.
While the allogeneic T cell proliferation induced by the entire
DC-IL-10 population was approximately 30% of that stimulated by DCims,
allogeneic MLR responses driven by the ILThigh DC subset were reduced
to 8% of the allostimulatory capacity of DCims, although secretion
of the inhibitory cytokine IL-10 and other Th1/Th2-associated cytokines
was similar in these cells.},
issn = {1521-4141},
keywords = {Dendritic cells, Interleukin 10, Gene profiling, Immunoreceptors},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200324732}
}
@ARTICLE{Velazquez2005,
author = {Velázquez, Francisco and Parro, VÃctor and De Lorenzo, VÃctor},
title = {Inferring the genetic network of m-xylene metabolism through expression
profiling of the xyl genes of Pseudomonas putida mt-2},
journal = {Molecular Microbiology},
year = {2005},
volume = {57},
pages = {1557--1569},
number = {6},
abstract = {Summary A subgenomic array of structural and regulatory genes of the
TOL plasmid pWW0 of Pseudomonas putida mt-2 has been constructed
to sort out the interplay between m-xylene catabolism and the environmental
stress brought about by this aromatic chemical. To this end, xyl
sequences were spotted along with groups of selected P. putida genes,
the transcription of which become descriptors of distinct physiological
conditions. The expression of the TOL pathway in response to pathway
substrates was thus profiled, uncovering a regulatory network that
overcomes and expands the predictions made by projecting known data
from individual promoters. First, post-transcriptional checks appear
to mitigate the burden caused by non-productive induction of the
TOL operons. Second, the fate of different segments of the polycistronic
mRNAs from the upper and lower TOL operons varies depending on the
metabolism of their inducers. Finally, m-xylene triggers a noticeable
heat shock, the onset of which does interfere with optimal expression
of catabolic genes. These results reveal a degree of regulatory partnership
between TOL plasmid-encoded functions and host physiology that go
beyond transcription initiation control.},
issn = {1365-2958},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2005.04787.x}
}
@ARTICLE{Velazquez-Fernandez2005,
author = {Velázquez-Fernández, David and Laurell, Cecilia and Geli, Janos and
Höög, Anders and Odeberg, Jacob and Kjellman, Magnus and Lundeberg,
Joakim and Hamberger, Bertil and Nilsson, Peter and Bäckdahl, Martin},
title = {Expression profiling of adrenocortical neoplasms suggests a molecular
signature of malignancy},
journal = {Surgery},
year = {2005},
volume = {138},
pages = {1087--1094},
number = {6},
month = dec,
abstract = {Background Distinguishing between adrenocortical adenomas and carcinomas
is often difficult. Our aim was to investigate the differences in
transcriptional profiles between benign and malignant adrenocortical
neoplasms using complementary DNA microarray techniques.Methods We
studied 7 patients with adrenocortical carcinomas and 13 with adenomas.
Histopathology was reviewed in all patients; clinical follow-up was
at least 1 year. Hybridizations were performed in duplicate against
RNA reference. Expression levels were analyzed in the R environment
for statistical computing with the use of aroma, limma, statistics,
and class packages.Results Transcriptional profiles were homogeneous
among adenomas, while carcinomas were much more heterogeneous. Hierarchical
clustering and self-organizing maps could separate clearly carcinomas
from adenomas. Among genes that were most significantly upregulated
in carcinomas were 2 ubiquitin-related genes (USP4 and UFD1L) and
several insulinlike growth factor-related genes (IGF2, IGF2R, IGFBP3
and IGFBP6). Among genes that were most significantly downregulated
in carcinomas were a cytokine gene (CXCL10), several genes related
to cell metabolism (RARRES2, ALDH1A1, CYBRD1 and GSTA4), and the
cadherin 2 gene (CDH2).Conclusions Through the use of cDNA arrays,
adrenocortical adenomas and carcinomas appear to be clearly distinguishable
on the basis of their specific molecular signature. The biologic
importance of the up- and downregulated genes is yet to be determined.},
issn = {0039-6060},
url = {http://www.sciencedirect.com/science/article/B6WXC-4HTKSJG-T/2/f3a4b9abc99cda3f7509d37d0bc78f76}
}
@ARTICLE{Ven2006,
author = {van der Ven, Karlijn and Keil, Dorien and Moens, Lotte N. and Hummelen,
Paul Van and van Remortel, Piet and Maras, Marleen and De Coen, Wim},
title = {Effects of the antidepressant mianserin in zebrafish: Molecular markers
of endocrine disruption},
journal = {Chemosphere},
year = {2006},
volume = {65},
pages = {1836--1845},
number = {10},
month = dec,
abstract = {Due to their environmental occurrence and intrinsic biological activity,
human pharmaceuticals have received increasing attention from environmental
and health agencies. Of particular, ecotoxicological concern are
drugs that affect nervous- and endocrine-systems. Zebrafish genome-wide
oligo arrays are used to collect mechanistic information on mianserin-induced
changes in gene expression in zebrafish. Gene expression analysis
in brain and gonad tissue clearly demonstrated the estrogenic activity
of mianserin and its potency to disrupt normal endocrine (estrogenic)
signaling, based on induction of molecular biomarkers of estrogenicity
(e.g., vitellogenin1 and zona pellucida proteins). The possible mechanism
underlying this estrogenic activity of mianserin is disturbance of
the Hypothalamo-Pituitary-Gonadal (HPG) axis by direct interference
of mianserin with the serotonergic and adrenergic systems in the
brain of zebrafish. Taking into account the importance of the HPG-axis,
and considering the concept of [`]critical window of exposure', our
results reveal the importance for more elaborate testing of endocrine
disruptive effects of aquatic antidepressants at different lifestages
and during longer exposure periods (e.g., life cycle studies). Although
there is a low concordance between the gene expression results in
this study and previous cDNA microarray hybridizations, the global
mechanistic expression patterns are similar in both platforms. This
argues in favor of pathway-driven analysis of gene expression results
compared to gene-per-gene analysis.},
issn = {0045-6535},
keywords = {Oligo microarray, Zebrafish, Pharmaceuticals, Mianserin, Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/B6V74-4K4219S-2/2/79f39a3bb67a0d64254c4cd239f504f8}
}
@ARTICLE{Ven2008,
author = {van de Ven, Rieneke and Scheffer, George L. and Reurs, Anneke W.
and Lindenberg, Jelle J. and Oerlemans, Ruud and Jansen, Gerrit and
Gillet, Jean-Pierre and Glasgow, Joel N. and Pereboev, Alexander
and Curiel, David T. and Scheper, Rik J. and de Gruijl, Tanja D.},
title = {A role for multidrug resistance protein 4 (MRP4; ABCC4) in human
dendritic cell migration},
journal = {Blood},
year = {2008},
volume = {112},
pages = {2353--2359},
number = {6},
month = sep,
abstract = {The capacity of dendritic cells (DCs) to migrate from peripheral organs
to lymph nodes (LNs) is important in the initiation of a T cell-mediated
immune response. The ATP-binding cassette (ABC) transporters P-glycoprotein
(P-gp; ABCB1) and the multidrug resistance protein 1 (MRP1; ABCC1)
have been shown to play a role in both human and murine DC migration.
Here we show that a more recently discovered family member, MRP4
(ABCC4), is expressed on both epidermal and dermal human skin DCs
and contributes to the migratory capacity of DCs. Pharmacological
inhibition of MRP4 activity or down-regulation through RNAi in DCs
resulted in reduced migration of DCs from human skin explants and
of in vitro generated Langerhans cells. The responsible MRP4 substrate
remains to be identified as exogenous addition of MRP4's known substrates
prostaglandin E2, leukotriene B4 and D4, or cyclic nucleotides (all
previously implicated in DC migration) could not restore migration.
This notwithstanding, our data show that MRP4 is an important protein,
significantly contributing to human DC migration toward the draining
lymph nodes, and therefore relevant for the initiation of an immune
response and a possible target for immunotherapy.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/6/2353}
}
@ARTICLE{Vendelin2006,
author = {Vendelin, Johanna and Bruce, Sara and Holopainen, Paivi and Pulkkinen,
Ville and Rytila, Paula and Pirskanen, Asta and Rehn, Marko and Laitinen,
Tarja and Laitinen, Lauri A. and Haahtela, Tari and Saarialho-Kere,
Ulpu and Laitinen, Annika and Kere, Juha},
title = {Downstream target genes of the neuropeptide S-NPSR1 pathway},
journal = {Hum. Mol. Genet.},
year = {2006},
volume = {15},
pages = {2923--2935},
number = {19},
month = oct,
abstract = {The neuropeptide S (NPS)-NPS receptor 1 (NPSR1) pathway has recently
been implicated in the pathogenesis of asthma. The purpose of this
study was to identify downstream gene targets regulated by NPSR1
upon NPS stimulation. A total of 104 genes were found significantly
up-regulated and 42 down-regulated by microarray analysis 6 h after
NPS administration. By Gene Ontology enrichment analysis, the categories
cell proliferation', morphogenesis' and immune response' were among
the most altered. A TMM microarray database comparison suggested
a common co-regulated pathway, which includes JUN/FOS oncogene homologs,
early growth response genes, nuclear receptor subfamily 4 members
and dual specificity phosphatases. The expression of four up-regulated
genes, matrix metallopeptidase 10 (MMP10), INHBA (activin A), interleukin
8 (IL8) and EPH receptor A2 (EPHA2), exhibited a significant NPS
dose-response relationship as confirmed by quantitative reverse-transcriptase-PCR
and for MMP10 by immunoassay. Immunohistochemical analyses revealed
that MMP10 and TIMP metallopeptidase inhibitor 3 (TIMP3) were both
strongly expressed in bronchial epithelium, and macrophages and eosinophils
expressed MMP10 in asthmatic sputum samples. Because remodeling of
airway epithelium is a feature of chronic asthma, the up-regulation
of MMP10 and TIMP3 by NPS-NPSR1 signaling may be of relevance in
the pathogenesis of asthma.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/15/19/2923}
}
@ARTICLE{Vendrell2008,
author = {Vendrell, Julie and Robertson, Katherine and Ravel, Patrice and Bray,
Susan and Bajard, Agathe and Purdie, Colin and Nguyen, Catherine
and Hadad, Sirwan and Bieche, Ivan and Chabaud, Sylvie and Bachelot,
Thomas and Thompson, Alastair and Cohen, Pascale},
title = {A candidate molecular signature associated with tamoxifen failure
in primary breast cancer},
journal = {Breast Cancer Research},
year = {2008},
volume = {10},
pages = {R88},
number = {5},
note = {See related editorial by Sims and Bartlett, http://breast-cancer-research.com/content/10/6/115},
abstract = {INTRODUCTION:Few markers are available that can predict response to
tamoxifen treatment in estrogen receptor (ER)-positive breast cancers.
Identification of such markers would be clinically useful. We attempted
to identify molecular markers associated with tamoxifen failure in
breast cancer.METHODS:Eighteen initially ER-positive patients treated
with tamoxifen requiring salvage surgery (tamoxifen failure [TF]
patients) were compared with 17 patients who were disease free 5
years after surgery plus tamoxifen adjuvant therapy (control patients).
cDNA microarray, real-time quantitative PCR, and immunohistochemistry
on tissue microarrays were used to generate and confirm a gene signature
associated with tamoxifen failure. An independent series of 33 breast
tumor samples from patients who relapsed (n = 14) or did not relapse
(n = 19) under tamoxifen treatment from a different geographic location
was subsequently used to explore the gene expression signature identified.RESULTS:Using
a screening set of 18 tumor samples (from eight control patients
and 10 TF patients), a 47-gene signature discriminating between TF
and control samples was identified using cDNA arrays. In addition
to ESR1/ERa, the top-ranked genes selected by statistical cross-analyses
were MET, FOS, SNCG, IGFBP4, and BCL2, which were subsequently validated
in a larger set of tumor samples (from 17 control patients and 18
TF patients). Confirmation at the protein level by tissue microarray
immunohistochemistry was observed for ER-a, ?-synuclein, and insulin-like
growth factor binding protein 4 proteins in the 35 original samples.
In an independent series of breast tumor samples (19 nonrelapsing
and 14 relapsing), reduced expression of ESR1/ERa, IGFBP4, SNCG,
BCL2, and FOS was observed in the relapsing group and was associated
with a shorter overall survival. Low mRNA expression levels of ESR1/ERa,
BCL2, and FOS were also associated with a shorter relapse-free survival
(RFS). Using a Cox multivariate regression analysis, we identified
BCL2 and FOS as independent prognostic markers associated with RFS.
Finally, the BCL2/FOS signature was demonstrated to have more accurate
prognostic value for RFS than ESR1/ERa alone (likelihood ratio test).CONCLUSIONS:We
identified molecular markers including a BCL2/FOS signature associated
with tamoxifen failure; these markers may have clinical potential
in the management of ER-positive breast cancer.},
doi = {10.1186/bcr2158},
issn = {1465-5411},
pubmedid = {18928543},
url = {http://breast-cancer-research.com/content/10/5/R88}
}
@ARTICLE{Vengeliene2006,
author = {Vengeliene, Valentina and Leonardi-Essmann, Fernando and Perreau-Lenz,
Stephanie and Gebicke-Haerter, Peter and Drescher, Karla and Gross,
Gerhard and Spanagel, Rainer},
title = {The dopamine D3 receptor plays an essential role in alcohol-seeking
and relapse},
journal = {FASEB J},
year = {2006},
volume = {20},
pages = {2223--2233},
number = {13},
month = nov,
abstract = {Our study aimed to identify new candidate genes, which might be involved
in alcohol craving and relapse. To find changes in gene expression
after long-term alcohol consumption, we studied gene expression profiles
in the striatal dopamine system by using DNA microarrays of two different
alcohol-preferring rat lines (HAD and P). Our data revealed an up-regulation
of the dopamine D3 receptor (D3R) after 1 yr of voluntary alcohol
consumption in the striatum of alcohol preferring rats that was confirmed
by qRT-polymerase chain reaction. This finding was further supported
by the finding of up-regulated striatal D3R mRNA in nonselected Wistar
rats after long-term alcohol consumption when compared with age-matched
control animals. We further examined the role of the D3R in mediating
alcohol relapse behavior using the alcohol deprivation effect (ADE)
model in long-term alcohol drinking Wistar rats and the model of
cue-induced reinstatement of alcohol-seeking behavior using the selective
D3R antagonist SB-277011-A (0, 1, 3, and 10 mg/kg) and the partial
agonist BP 897 (0, 0.1, 1, and 3 mg/kg). Both treatments caused a
dose-dependent reduction of relapse-like drinking in the ADE model
as well as a decrease in cue-induced ethanol-seeking behavior. We
conclude that long-term alcohol consumption leads to an up-regulation
of the dopamine D3R that may contribute to alcohol-seeking and relapse.
We therefore suggest that selective antagonists of this pharmacological
target provide a specific treatment approach to reduce alcohol craving
and relapse behavior.--Vengeliene, V., Leonardi-Essmann, F., Perreau-Lenz,
S., Gebicke-Haerter, P., Drescher, K., Gross, G., Spanagel, R. The
dopamine D3 receptor plays an essential role in alcohol-seeking and
relapse.},
url = {http://www.fasebj.org/cgi/content/abstract/20/13/2223}
}
@ARTICLE{Vengellur2005,
author = {Vengellur, A. and Phillips, J. M. and Hogenesch, J. B. and LaPres,
J. J.},
title = {Gene expression profiling of hypoxia signaling in human hepatocellular
carcinoma cells},
journal = {Physiol Genomics},
year = {2005},
volume = {22},
pages = {308--318},
number = {3},
month = aug,
abstract = {Cellular, local, and organismal responses to low O2 availability occur
during processes such as anaerobic metabolism and wound healing and
pathological conditions such as stroke and cancer. These responses
include increases in glycolytic activity, vascularization, breathing,
and red blood cell production. These responses are mediated in part
by the hypoxia-inducible factors (HIFs), which receive information
on O2 levels from a group of iron- and O2-dependent hydroxylases.
Hypoxia mimics, such as cobalt chloride, nickel chloride, and deferoxamine,
act to simulate hypoxia by altering the iron status of these hydroxylases.
To determine whether these mimics are appropriate substitutes for
the lower O2 tension evoked naturally, we compared transcriptional
responses of a Hep3B cell line using high-density oligonucleotide
arrays. A battery of core genes was identified that was shared by
all four treatments (hypoxia, cobalt, nickel, and deferoxamine) including
glycolytic enzymes, cell cycle regulators, and apoptotic genes. Importantly,
cobalt, nickel, and deferoxamine influenced transcription of distinct
sets of genes that were not affected by cellular hypoxia. These global
responses to hypoxia indicate a balancing act between adaptation
and programmed cell death and suggest caution in the use of hypoxia
mimics as substitutes for the low O2 tension that occurs in vivo.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/22/3/308}
}
@ARTICLE{Venier2009,
author = {Venier, Paola and De Pittà, Cristiano and Bernante, Filippo and Varotto,
Laura and De Nardi, Barbara and Bovo, Giuseppe and Roch, Philippe
and Novoa, Beatriz and Figueras, Antonio and Pallavicini, Alberto
and Lanfranchi, Gerolamo},
title = {MytiBase: a knowledgebase of mussel (M. galloprovincialis) transcribed
sequences},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {72},
number = {1},
abstract = {BACKGROUND:Although Bivalves are among the most studied marine organisms
due to their ecological role, economic importance and use in pollution
biomonitoring, very little information is available on the genome
sequences of mussels. This study reports the functional analysis
of a large-scale Expressed Sequence Tag (EST) sequencing from different
tissues of Mytilus galloprovincialis (the Mediterranean mussel) challenged
with toxic pollutants, temperature and potentially pathogenic bacteria.RESULTS:We
have constructed and sequenced seventeen cDNA libraries from different
Mediterranean mussel tissues: gills, digestive gland, foot, anterior
and posterior adductor muscle, mantle and haemocytes. A total of
24,939 clones were sequenced from these libraries generating 18,788
high-quality ESTs which were assembled into 2,446 overlapping clusters
and 4,666 singletons resulting in a total of 7,112 non-redundant
sequences. In particular, a high-quality normalized cDNA library
(Nor01) was constructed as determined by the high rate of gene discovery
(65.6%). Bioinformatic screening of the non-redundant M. galloprovincialis
sequences identified 159 microsatellite-containing ESTs. Clusters,
consensuses, related similarities and gene ontology searches have
been organized in a dedicated, searchable database http://mussel.cribi.unipd.it.CONCLUSION:We
defined the first species-specific catalogue of M. galloprovincialis
ESTs including 7,112 unique transcribed sequences. Putative microsatellite
markers were identified. This annotated catalogue represents a valuable
platform for expression studies, marker validation and genetic linkage
analysis for investigations in the biology of Mediterranean mussels.},
doi = {10.1186/1471-2164-10-72},
issn = {1471-2164},
pubmedid = {19203376},
url = {http://www.biomedcentral.com/1471-2164/10/72}
}
@ARTICLE{Venier2006,
author = {Venier, Paola and De Pittà, Cristiano and Pallavicini, Alberto and
Marsano, Francesco and Varotto, Laura and Romualdi, Chiara and Dondero,
Francesco and Viarengo, Aldo and Lanfranchi, Gerolamo},
title = {Development of mussel mRNA profiling: Can gene expression trends
reveal coastal water pollution?},
journal = {Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis},
year = {2006},
volume = {602},
pages = {121--134},
number = {1-2},
month = dec,
abstract = {Marine bivalves of the genus Mytilus are intertidal filter-feeders
commonly used as biosensors of coastal pollution. Mussels adjust
their functions to ordinary environmental changes, e.g. temperature
fluctuations and emersion-related hypoxia, and react to various contaminants,
accumulated from the surrounding water and defining a potential health
risk for sea-food consumers. Despite the increasing use of mussels
in environmental monitoring, their genome and gene functions are
largely unexplored. Hence, we started the systematic identification
of expressed sequence tags and prepared a cDNA microarray of Mytilus
galloprovincialis including 1714 mussel probes (76% singletons, ~50%
putatively identified transcripts) plus unrelated controls. To assess
the potential use of the gene set represented in MytArray 1.0, we
tested different tissues and groups of mussels. The resulting data
highlighted the transcriptional specificity of the mussel tissues.
Further testing of the most responsive digestive gland allowed correct
classification of mussels treated with mixtures of heavy metals or
organic contaminants (expression changes of specific genes discriminated
the two pollutant cocktails). Similar analyses made a distinction
possible between mussels living in the Venice lagoon (Italy) at the
petrochemical district and mussels close to the open sea. The suggestive
presence of gene markers tracing organic contaminants more than heavy
metals in mussels from the industrial district is consistent with
reported trends of chemical contamination. Further study is necessary
in order to understand how much gene expression profiles can disclose
the signatures of pollutants in mussel cells and tissues. Nevertheless,
the gene expression patterns described in this paper support a wider
characterization of the mussel transcriptome and point to the development
of novel environmental metrics.},
issn = {0027-5107},
keywords = {Mytilus galloprovincialis, cDNA microarray, Coastal water pollution,
Gene expression profiles, Heavy metals, Aromatic and chlorinated
organic compounds},
url = {http://www.sciencedirect.com/science/article/B6T2C-4M0J50V-1/2/9b493b4ceab5a0fad08d2f468505f51d}
}
@ARTICLE{Venier2011,
author = {Venier, Paola and Varotto, Laura and Rosani, Umberto and Millino,
Caterina and Celegato, Barbara and Bernante, Filippo and Lanfranchi,
Gerolamo and Novoa, Beatriz and Roch, Philippe and Figueras, Antonio
and Pallavicini, Alberto},
title = {Insights into the innate immunity of the Mediterranean mussel Mytilus
galloprovincialis},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {69},
number = {1},
abstract = {BACKGROUND:Sessile bivalves of the genus Mytilus are suspension feeders
relatively tolerant to a wide range of environmental changes, used
as sentinels in ecotoxicological investigations and marketed worldwide
as seafood. Mortality events caused by infective agents and parasites
apparently occur less in mussels than in other bivalves but the molecular
basis of such evidence is unknown. The arrangement of Mytibase, interactive
catalogue of 7,112 transcripts of M. galloprovincialis, offered us
the opportunity to look for gene sequences relevant to the host defences,
in particular the innate immunity related genes.RESULTS:We have explored
and described the Mytibase sequence clusters and singletons having
a putative role in recognition, intracellular signalling, and neutralization
of potential pathogens in M. galloprovincialis. Automatically assisted
searches of protein signatures and manually cured sequence analysis
confirmed the molecular diversity of recognition/effector molecules
such as the antimicrobial peptides and many carbohydrate binding
proteins. Molecular motifs identifying complement C1q, C-type lectins
and fibrinogen-like transcripts emerged as the most abundant in the
Mytibase collection whereas, conversely, sequence motifs denoting
the regulatory cytokine MIF and cytokine-related transcripts represent
singular and unexpected findings. Using a cross-search strategy,
1,820 putatively immune-related sequences were selected to design
oligonucleotide probes and define a species-specific Immunochip (DNA
microarray). The Immunochip performance was tested with hemolymph
RNAs from mussels injected with Vibrio splendidus at 3 and 48 hours
post-treatment. A total of 143 and 262 differentially expressed genes
exemplify the early and late hemocyte response of the Vibrio-challenged
mussels, respectively, with AMP trends confirmed by qPCR and clear
modulation of interrelated signalling pathways.CONCLUSIONS:The Mytibase
collection is rich in gene transcripts modulated in response to antigenic
stimuli and represents an interesting window for looking at the mussel
immunome (transcriptomes mediating the mussel response to non-self
or abnormal antigens). On this basis, we have defined a new microarray
platform, a mussel Immunochip, as a flexible tool for the experimental
validation of immune-candidate sequences, and tested its performance
on Vibrio-activated mussel hemocytes. The microarray platform and
related expression data can be regarded as a step forward in the
study of the adaptive response of the Mytilus species to an evolving
microbial world.},
doi = {10.1186/1471-2164-12-69},
issn = {1471-2164},
pubmedid = {21269501},
url = {http://www.biomedcentral.com/1471-2164/12/69}
}
@ARTICLE{Venkatachalam2008,
author = {Venkatachalam, Kaliyamurthi and Mummidi, Srinivas and Cortez, Dolores
M. and Prabhu, Sumanth D. and Valente, Anthony J. and Chandrasekar,
Bysani},
title = {Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent
interleukin-17 expression in primary mouse cardiac fibroblasts},
journal = {Am J Physiol Heart Circ Physiol},
year = {2008},
volume = {294},
pages = {H2078--2087},
number = {5},
month = may,
abstract = {We investigated the expression of the proinflammatory cytokine interleukin
(IL)-17 in cardiac fibroblasts and its induction by high glucose
(HG). Our results show that primary mouse cardiac fibroblasts (mCFs)
secrete low basal levels of IL-17 and that HG (25 mM D-glucose) as
opposed to low glucose (5 mM D-glucose + 20 mM mannitol) significantly
enhances its secretion. HG induces IL-17 mRNA expression by both
transcriptional and posttranscriptional mechanisms. HG induces phosphoinositide
3- kinase [PI3K; inhibited by adenoviral (Ad).dominant negative (dn)PI3Kp85],
Akt (inhibited by Ad.dnAkt1), and ERK (inhibited by PD-98059) activation
and induces IL-17 expression via PI3K[->]Akt[->]ERK-dependent
signaling. Moreover, mCFs express both IL-17 receptors A and C, and
although IL-17RA is upregulated, HG fails to modulate IL-17RC expression.
Furthermore, IL-17 stimulates net collagen production by mCFs. Pretreatment
with the phytoalexin resveratrol blocks HG-induced PI3K-, Akt-, and
ERK-dependent IL-17 expression. These results demonstrate that 1)
cardiac fibroblasts express IL-17 and its receptors; 2) HG upregulates
IL-17 and IL-17RA, suggesting a positive amplification loop in IL-17
signaling in hyperglycemia; 3) IL-17 enhances net collagen production;
and 4) resveratrol can inhibit these HG-induced changes. Thus, in
hyperglycemic conditions, IL-17 may potentiate myocardial inflammation,
injury, and remodeling through autocrine and paracrine mechanisms,
and resveratrol has therapeutic potential in ameliorating this effect.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/294/5/H2078}
}
@ARTICLE{Venkatachalam2009,
author = {Venkatachalam, Kaliyamurthi and Prabhu, Sumanth D. and Reddy, Venkatapuram
Seenu and Boylston, William H. and Valente, Anthony J. and Chandrasekar,
Bysani},
title = {Neutralization of Interleukin-18 Ameliorates Ischemia/Reperfusion-induced
Myocardial Injury},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {7853--7865},
number = {12},
month = mar,
abstract = {Ischemia/reperfusion (I/R) injury is characterized by the induction
of oxidative stress and proinflammatory cytokine expression. Recently
demonstrating that oxidative stress and TNF-{alpha} each stimulate
interleukin (IL)-18 expression in cardiomyocytes, we hypothesized
that I/R also induces IL-18 expression and thus exacerbates inflammation
and tissue damage. Neutralization of IL-18 signaling should therefore
diminish tissue injury following I/R. I/R studies were performed
using a chronically instrumented closed chest mouse model. Male C57BL/6
mice underwent 30 min of ischemia by LAD coronary artery ligation
followed by various periods of reperfusion. Sham-operated or ischemia-only
mice served as controls. A subset of animals was treated with IL-18-neutralizing
antibodies 1 h prior to LAD ligation. Ischemic LV tissue was used
for analysis. Our results demonstrate that, compared with sham operation
and ischemia alone, I/R significantly increased (i) oxidative stress
(increased MDA/4-HNE levels), (ii) neutrophil infiltration (increased
MPO activity), (iii) NF-{kappa}B DNA binding activity (p50, p65),
and (iv) increased expression of IL-18R{beta}, but not IL-18R{alpha}
or IL-18BP transcripts. Administration of IL-18-neutralizing antibodies
significantly reduced I/R injury measured by reduced infarct size
(versus control IgG). In isolated adult mouse cardiomyocytes, simulated
ischemia/reperfusion enhanced oxidative stress and biologically active
IL-18 expression via IKK-dependent NF-{kappa}B activation. These
results indicate that IL-18 plays a critical role in I/R injury and
thus represents a promising therapeutic target.},
url = {http://www.jbc.org/cgi/content/abstract/284/12/7853}
}
@ARTICLE{Venkatachalam2009a,
author = {Venkatachalam, Kaliyamurthi and Venkatesan, Balachandar and Valente,
Anthony J. and Melby, Peter C. and Nandish, Sailesh and Reusch, Jane
E. B. and Clark, Robert A. and Chandrasekar, Bysani},
title = {WISP1, a Pro-mitogenic, Pro-survival Factor, Mediates Tumor Necrosis
Factor-{alpha} (TNF-{alpha})-stimulated Cardiac Fibroblast Proliferation
but Inhibits TNF-{alpha}-induced Cardiomyocyte Death},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {14414--14427},
number = {21},
month = may,
abstract = {WNT1-inducible signaling pathway protein-1 (WISP1), a member of the
CYR61/CTGF/Nov family of growth factors, can mediate cell growth,
transformation, and survival. Previously we demonstrated that WISP1
is up-regulated in post-infarct heart, stimulates cardiac fibroblast
proliferation, and is induced by the proinflammatory cytokine tumor
necrosis factor-{alpha} (TNF-{alpha}). Here we investigated (i) the
localization of TNF-{alpha} and WISP1 in post-infarct heart, (ii)
the mechanism of TNF-{alpha}-mediated WISP1 induction in primary
human cardiac fibroblasts (CF), (iii) the role of WISP1 in TNF-{alpha}-mediated
CF proliferation and collagen production, and (iv) the effects of
WISP1 on TNF-{alpha}-mediated cardiomyocyte death. TNF-{alpha} and
WISP1 expressions were increased in the border zones and non-ischemic
remote regions of the post-ischemic heart. In CF, TNF-{alpha} potently
induced WISP1 expression in cyclic AMP response element-binding protein
(CREB)-dependent manner. TNF-{alpha} induced CREB phosphorylation
in vitro and DNA binding and reporter gene activities in vivo. TNF-{alpha}
induced CREB activation via ERK1/2, and inhibition of ERK1/2 and
CREB blunted TNF-{alpha}-mediated WISP1 induction. Most importantly,
WISP1 knockdown attenuated TNF-{alpha} stimulated collagen production
and CF proliferation. Furthermore, WISP1 attenuated TNF-{alpha}-mediated
cardiomyocyte death, thus demonstrating pro-mitogenic and pro-survival
effects for WISP1 in myocardial constituent cells. Our results suggest
that a TNF-{alpha}/WISP1 signaling pathway may contribute to post-infarct
cardiac remodeling, a condition characterized by fibrosis and progressive
cardiomyocyte loss.},
url = {http://www.jbc.org/cgi/content/abstract/284/21/14414}
}
@ARTICLE{Venkatesan2009,
author = {Venkatesan, Balachandar and Valente, Anthony J. and Reddy, Venkatapuram
Seenu and Siwik, Deborah A. and Chandrasekar, Bysani},
title = {Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth
muscle cell migration},
journal = {Am J Physiol Heart Circ Physiol},
year = {2009},
volume = {297},
pages = {H874--886},
number = {2},
month = aug,
abstract = {Vascular smooth muscle cell (SMC) migration is an important mechanism
in atherogenesis and postangioplasty arterial remodeling. Previously,
we demonstrated that the proinflammatory cytokine interleukin (IL)-18
is a potent inducer of SMC migration. Since extracellular matrix
metalloproteinase inducer (EMMPRIN) stimulates ECM degradation and
facilitates cell migration, we investigated whether IL-18 and EMMPRIN
regulate each other's expression, whether their cross talk induces
SMC migration, and whether the phytoalexin resveratrol inhibits IL-18-EMMPRIN
signaling and SMC migration. Our studies demonstrate that 1) IL-18
induces EMMPRIN mRNA and protein expressions and stimulates EMMPRIN
secretion from human aortic SMCs; 2) IL-18 stimulates EMMPRIN expression
via oxidative stress and phosphatidylinositol 3-kinase (PI3K)-Akt-ERK
signaling; 3) IL-18-stimulated SMC migration is significantly blunted
by EMMPRIN knockdown, EMMPRIN function-blocking antibodies, or adenoviral
transduction of mutant EMMPRIN; 4) conversely, EMMPRIN stimulates
IL-18 expression and secretion via PI3K, Akt, and ERK; and 5) resveratrol
attenuates IL-18- and EMMPRIN-mediated PI3K, Akt, and ERK activations;
blunts IL-18-mediated oxidative stress; blocks IL-18-EMMPRIN cross-regulation;
and inhibits SMC migration. Collectively, our results demonstrate
that the coexpression and regulation of IL-18 and EMMPRIN in the
vessel wall may amplify the inflammatory cascade and promote atherosclerosis
and remodeling. Resveratrol, via its antioxidant and anti-inflammatory
properties, has the potential to inhibit the progression of atherosclerosis
by blocking IL-18 and EMMPRIN cross-regulation and SMC migration.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/297/2/H874}
}
@ARTICLE{Venkatesh2006,
author = {Venkatesh, Balakrishnan and Babujee, Lavanya and Liu, Hui and Hedley,
Pete and Fujikawa, Takashi and Birch, Paul and Toth, Ian and Tsuyumu,
Shinji},
title = {The Erwinia chrysanthemi 3937 PhoQ Sensor Kinase Regulates Several
Virulence Determinants},
journal = {J. Bacteriol.},
year = {2006},
volume = {188},
pages = {3088--3098},
number = {8},
month = apr,
abstract = {The PhoPQ two-component system regulates virulence factors in Erwinia
chrysanthemi, a pectinolytic enterobacterium that causes soft rot
in several plant species. We characterized the effect of a mutation
in phoQ, the gene encoding the sensor kinase PhoQ of the PhoPQ two-component
regulatory system, on the global transcriptional profile of E. chrysanthemi
using cDNA microarrays and further confirmed our results by quantitative
reverse transcription-PCR analysis. Our results indicate that a mutation
in phoQ affects transcription of at least 40 genes, even in the absence
of inducing conditions. Enhanced expression of several genes involved
in iron metabolism was observed in the mutant, including that of
the acs operon that is involved in achromobactin biosynthesis and
transport. This siderophore is required for full virulence of E.
chrysanthemi, and its expression is governed by the global repressor
protein Fur. Changes in gene expression were also observed for membrane
transporters, stress-related genes, toxins, and transcriptional regulators.
Our results indicate that the PhoPQ system governs the expression
of several additional virulence factors and may also be involved
in interactions with other regulatory systems.},
url = {http://jb.asm.org/cgi/content/abstract/188/8/3088}
}
@ARTICLE{Venken2005,
author = {Venken, Katrien and Schuit, Frans and Van Lommel, Leentje and Tsukamoto,
Katsura and Kopchick, John J and Coschigano, Karen and Ohlsson, Claes
and Movérare, Sofia and Boonen, Steven and Bouillon, Roger and Vanderschueren,
Dirk},
title = {Growth Without Growth Hormone Receptor: Estradiol Is a Major Growth
Hormone-Independent Regulator of Hepatic IGF-I Synthesis},
journal = {J Bone Miner Res},
year = {2005},
volume = {20},
pages = {2138--2149},
number = {12},
abstract = {Abstract 10.1359/JBMR.050811.abs The role of estrogens in the regulation
of pubertal growth independently of GH and its receptor was studied
in male mice with disrupted GHRKO. E2 rescued skeletal growth rates
in GHRKO associated with an increase in hepatic and serum IGF-I.
These data show that E2 rescues pubertal growth during GH resistance
through a novel mechanism of GHR-independent stimulation of hepatic
IGF-I production. Introduction: Growth hormone (GH) and estrogen
play a pivotal role in pubertal growth and bone mineral acquisition.
Estrogens can affect GH secretion and thereby provide a GH-dependent
mechanism for their effects on skeletal growth. It is presently unclear
if or to what extent estrogens are able to regulate pubertal growth
and bone mineral accrual independently of GH and its receptor. Materials
and Methods: Estradiol (E2; 0.03 μg/day by subcutaneous silastic
implants) was administered to orchidectomized (ORX) male mice with
disrupted GHR (GHRKO) and corresponding WTs during late puberty (6–10
weeks). Longitudinal and radial bone growth, IGF-I in serum and its
expression in liver, muscle, and bone, and liver gene expression
were studied by histomorphometry, RIA, RT-PCR, microarrays, and Western
blotting, respectively. Results: E2 stimulated not only longitudinal
(femur length and growth plate thickness) and radial growth (cortical
thickness and periosteal perimeter), but also rescued longitudinal
and periosteal growth rates in ORX GHRKO, whereas no significant
changes occurred in WT. E2 thereby upregulated serum IGF-I and liver
IGF-I synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas
IGF-I synthesis in femur or muscle was unaffected. Study of the underlying
mechanism of the stimulation of hepatic IGF-I expression showed that
E2 restored downregulated receptor signaling systems, such as the
estrogen receptor α and the prolactin receptor. E2 thereby recovered
the Janus kinase (JAK)/signal transducers and activators of transcription
(STAT) pathway as evidenced by a significantly increased activation
of the transcription factor STAT5 in ORX GHRKO. Conclusions: Our
data show a stimulation of skeletal growth through upregulation of
hepatic IGF-I by a hormone other than GH. E2 rescues pubertal skeletal
growth during GH resistance through a novel mechanism of GHR-independent
stimulation of IGF-I synthesis in the liver.},
issn = {1523-4681},
keywords = {growth hormone receptor knockout mouse, bone, estrogens, IGF-I, liver
gene expression},
publisher = {John Wiley and Sons and The American Society for Bone and Mineral
Research (ASBMR)},
url = {http://dx.doi.org/10.1359/JBMR.050811}
}
@ARTICLE{Vennemann2010,
author = {Vennemann, Marielle and Koppelkamm, Antje},
title = {Postmortem mRNA profiling II: Practical considerations},
journal = {Forensic Science International},
year = {2010},
volume = {203},
pages = {76--82},
number = {1-3},
month = dec,
abstract = {Using human postmortem tissues for gene expression studies is particularly
challenging. Besides the problem of impaired RNA one has to face
a very high degree of biological variance within a sample set. Variations
of individual parameters like age, body mass, health, but also the
cause and circumstances of death and the postmortem interval lead
to a rather inhomogeneous collection of samples. To meet these problems
it is necessary to consider certain precautions before starting a
gene expression project. These precautions include the sample collection
and the determination of the RNA integrity, the number of replicates
needed and the methods used for reverse transcription and quantitative
polymerase chain reaction, but also the strategy for data normalisation
and data interpretation. In this article practical issues are discussed
to address some of the problems occurring in the work with postmortem
human samples obtained during medico-legal autopsy.},
booktitle = {Molecular Pathology in Forensic Medicine},
issn = {0379-0738},
keywords = {mRNA profiling, Postmortem tissue, Sample handling and processing,
Data interpretation},
url = {http://www.sciencedirect.com/science/article/pii/S0379073810003361}
}
@ARTICLE{Vennemann2010a,
author = {Vennemann, Marielle and Koppelkamm, Antje},
title = {mRNA profiling in forensic genetics I: Possibilities and limitations},
journal = {Forensic Sci Int},
year = {2010},
volume = {203},
pages = {71--75},
number = {1},
month = dec,
abstract = {Molecular investigations gain increasing interest in forensic medicine.
Examination of gene expression levels at the time point of death
might have the power to become a complementing tool to the current
methods for the determination of cause and circumstances of death.
This includes pathophysiological conditions of disease and injury
as well as the duration of agony or other premortem factors. Additionally,
recent developments in forensic genetics revealed that tissue specific
mRNAs can be used to determine the type of body fluid present in
a crime scene stain. Although RNA is known to be rather instable,
RNA could be extracted in adequate quality from tissue samples collected
during medico-legal autopsy. Nevertheless, working with human postmortem
tissue means to deal with highly variable RNA integrities. This review
aims to give a brief overview of the possible advantages of postmortem
mRNA profiling and to shed further light into the limitations of
this method arising from reduced RNA integrities.},
issn = {0379-0738},
keywords = {mRNA profiling, Post mortem tissue, Degradation, Body fluid identification,
Cause of death},
publisher = {Elsevier Science Ireland},
refid = {S0379-0738(10)00335-X},
url = {http://linkinghub.elsevier.com/retrieve/pii/S037907381000335X?showall=true}
}
@ARTICLE{Ventrella-Lucente2010,
author = {Ventrella-Lucente, Lisa F. and Unnikrishnan, Archana and Pilling,
Amanda B. and Patel, Hiral V. and Kushwaha, Deepa and Dombkowski,
Alan A. and Schmelz, Eva M. and Cabelof, Diane C. and Heydari, Ahmad
R.},
title = {Folate Deficiency Provides Protection against Colon Carcinogenesis
in DNA Polymerase {beta} Haploinsufficient Mice},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {19246--19258},
number = {25},
month = jun,
abstract = {Aging and DNA polymerase {beta} deficiency ({beta}-pol+/-) interact
to accelerate the development of malignant lymphomas and adenocarcinoma
and increase tumor bearing load in mice. Folate deficiency (FD) has
been shown to induce DNA damage repaired via the base excision repair
(BER) pathway. We anticipated that FD and BER deficiency would interact
to accelerate aberrant crypt foci (ACF) formation and tumor development
in {beta}-pol haploinsufficient animals. FD resulted in a significant
increase in ACF formation in wild type (WT) animals exposed to 1,2-dimethylhydrazine,
a known colon and liver carcinogen; however, FD reduced development
of ACF in {beta}-pol haploinsufficient mice. Prolonged feeding of
the FD diet resulted in advanced ACF formation and liver tumors in
wild type mice. However, FD attenuated onset and progression of ACF
and prevented liver tumorigenesis in {beta}-pol haploinsufficient
mice, i.e. FD provided protection against tumorigenesis in a BER-deficient
environment in all tissues where 1,2-dimethylhydrazine exerts its
damage. Here we show a distinct down-regulation in DNA repair pathways,
e.g. BER, nucleotide excision repair, and mismatch repair, and decline
in cell proliferation, as well as an up-regulation in poly(ADP-ribose)
polymerase, proapoptotic genes, and apoptosis in colons of FD {beta}-pol
haploinsufficient mice.},
url = {http://www.jbc.org/cgi/content/abstract/285/25/19246}
}
@ARTICLE{Venturini2007,
author = {Venturini, Letizia and Battmer, Karin and Castoldi, Mirco and Schultheis,
Beate and Hochhaus, Andreas and Muckenthaler, Martina U. and Ganser,
Arnold and Eder, Matthias and Scherr, Michaela},
title = {Expression of the miR-17-92 polycistron in chronic myeloid leukemia
(CML) CD34+ cells},
journal = {Blood},
year = {2007},
volume = {109},
pages = {4399--4405},
number = {10},
month = may,
abstract = {Aberrant micro RNA (miRNA) expression has been described in human
malignancies including B-cell lymphomas. We here report BCR-ABL-
and c-MYC-dependent regulation of miRNA expression in chronic myeloid
leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific
quantitative real-time reverse transcriptase-polymerase chain reaction
(miR-qRT-PCR). In 3 bcr-abl-positive cell lines, expression of miRNAs
encoded within the polycistronic miR-17-92 cluster is specifically
down-regulated (2- to 5-fold) by both imatinib treatment and anti-BCR-ABL
RNA interference (RNAi). In addition, anti-c-MYC RNAi reduces miR-17-92
expression in K562 cells in which miRNAs can specifically repress
reporter gene expression, as demonstrated by specific miRNA inhibition
with antagomirs. Furthermore, lentivirus-mediated overexpression
of polycistronic miRNAs in K562 cells confers increased proliferation,
partial resistance against anti-c-MYC RNAi, and enhanced sensitivity
to imatinib-induced cell death. Finally, we determined miR-17-92
expression in purified normal (n = 4), early chronic-phase (CP) (n
= 24), and blast-crisis (BC) (n = 7) CML CD34+ cells and found up-regulation
of polycistronic pri-miRNA transcripts in CML and mature miRNAs in
CP but not in BC CML. These data are in accordance with a BCR-ABL-c-MYC-miR-17-92
pathway that mediates enhanced miRNA expression in CP but not BC
CML CD34+ cells. Altered miRNA expression may contribute to the pathophysiology
of the disease and may provide potential targets for therapeutic
intervention.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/10/4399}
}
@ARTICLE{Verbrugghe2006,
author = {Verbrugghe, P and Waelput, W and Dieriks, B and Waeytens, A and Vandesompele,
J and Cuvelier, CA},
title = {Murine M cells express annexin V specifically},
journal = {J. Pathol.},
year = {2006},
volume = {209},
pages = {240--249},
number = {2},
abstract = {Abstract 10.1002/path.1970.abs The specialized epithelium covering
the lymphoid follicles of Peyer's patches in the gut mediates transcytosis
of antigens to the underlying immune cells, mainly through the membranous,
or M, cells. At present, the molecular processes involved in the
mucosal immune response, and in antigen transport across the follicle-associated
epithelium (FAE) and M cells, are poorly understood. To characterize
FAE and M cells, we compared the gene expression profiles of small
intestine FAE and villus epithelium (VE) in BALB/c mice by microarray
analysis; 91 genes were found to be up-regulated and four down-regulated
at least two-fold (p < 0.01) in the FAE. The differential expression
of a subset of these genes was shown to be confirmed by quantitative
RT-PCR. Using immunohistochemistry on BALB/c Peyer's patches, cathepsin
H and clusterin expression was increased in the FAE compared to the
VE. Moreover, we demonstrated M cell-specific expression of annexin
V, which has recently been reported to be important in endocytic
transport and membrane scaffolding, suggesting that annexin V has
a function in M cell-mediated transcytosis. Copyright © 2006 Pathological
Society of Great Britain and Ireland. Published by John Wiley & Sons,
Ltd.},
issn = {1096-9896},
keywords = {FAE, M cell, microarray, cathepsin H, clusterin, annexin V},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.1970}
}
@ARTICLE{Vercauteren2009,
author = {Vercauteren, Kristel and Gleyzer, Natalie and Scarpulla, Richard
C.},
title = {Short Hairpin RNA-mediated Silencing of PRC (PGC-1-related Coactivator)
Results in a Severe Respiratory Chain Deficiency Associated with
the Proliferation of Aberrant Mitochondria},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {2307--2319},
number = {4},
month = jan,
abstract = {PRC, a member of the PGC-1 coactivator family, is responsive to serum
growth factors and up-regulated in proliferating cells. Here, we
investigated its in vivo role by stably silencing PRC expression
with two different short hairpin RNAs (shRNA1 and shRNA4) that were
lentivirally introduced into U2OS cells. shRNA1 transductants exhibited
nearly complete knockdown of PRC protein, whereas shRNA4 transductants
expressed PRC protein at [~]15% of the control level. Complete PRC
silencing by shRNA1 resulted in a severe inhibition of respiratory
growth; reduced expression of respiratory protein subunits from complexes
I, II, III, and IV; markedly lower complex I and IV respiratory enzyme
levels; and diminished mitochondrial ATP production. Surprisingly,
shRNA1 transductants exhibited a striking proliferation of abnormal
mitochondria that were devoid of organized cristae and displayed
severe membrane abnormalities. Although shRNA4 transductants had
normal respiratory subunit expression and a moderately diminished
respiratory growth rate, both transductants showed markedly reduced
growth on glucose accompanied by inhibition of G1/S cell cycle progression.
Microarray analysis revealed striking overlaps in the genes affected
by PRC silencing in the two transductants, and the functional identities
of these overlapping genes were consistent with the observed mitochondrial
and cell growth phenotypes. The consistency between phenotype and
PRC expression levels in the two independent transductant lines argues
that the defects result from PRC silencing and not from off target
effects. These results support a role for PRC in the integration
of pathways directing mitochondrial respiratory function and cell
growth.},
url = {http://www.jbc.org/cgi/content/abstract/284/4/2307}
}
@ARTICLE{Verdoni2008,
author = {Verdoni, Angela M. and Aoyama, Natsuyo and Ikeda, Akihiro and Ikeda,
Sakae},
title = {Effect of destrin mutations on the gene expression profile in vivo},
journal = {Physiol Genomics},
year = {2008},
volume = {34},
pages = {9--21},
number = {1},
month = jun,
abstract = {Remodeling of the actin cytoskeleton through actin dynamics (assembly
and disassembly of filamentous actin) is known to be essential for
numerous basic biological processes. In addition, recent studies
have provided evidence that actin dynamics participate in the control
of gene expression. A spontaneous mouse mutant, corneal disease 1
(corn1), is deficient for a regulator of actin dynamics, destrin
(DSTN, also known as ADF), which causes epithelial hyperproliferation
and neovascularization in the cornea. Dstncorn1 mice exhibit an actin
dynamics defect in the corneal epithelial cells, offering an in vivo
model to investigate cellular mechanisms affected by the Dstn mutation
and resultant actin dynamics abnormalities. To examine the effect
of the Dstncorn1 mutation on the gene expression profile, we performed
a microarray analysis using the cornea from Dstncorn1 and wild-type
mice. A dramatic alteration of the gene expression profile was observed
in the Dstncorn1 cornea, with 1,226 annotated genes differentially
expressed. Functional annotation of these genes revealed that the
most significantly enriched functional categories are associated
with actin and/or cytoskeleton. Among genes that belong to these
categories, a considerable number of serum response factor target
genes were found, indicating the possible existence of an actin-SRF
pathway of transcriptional regulation in vivo. A comparative study
using an allelic mutant strain with milder corneal phenotypes suggested
that the level of filamentous actin may correlate with the level
of gene expression changes. Our study shows that Dstn mutations and
resultant actin dynamics abnormalities have a strong impact on the
gene expression profile in vivo.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/34/1/9}
}
@ARTICLE{Verdoy2011,
author = {Dolores Verdoy and Ziortza Barrenetxea and Javier Berganzo and Maria
Agirregabiria and Jesús M. Ruano-López and José M. Marimón and
Garbiñe OlabarrÃa},
title = {A novel Real Time micro PCR based Point-of-Care device for Salmonella
detection in human clinical samples},
journal = {Biosensors and Bioelectronics},
year = {2011},
pages = { - },
number = {0},
abstract = {Our POC (Point of Care) device is intended to be a diagnostic tool
for routine use in the clinical sector. The validation of the whole
procedure, including bacterial genomic DNA isolation and the Real
Time detection of Salmonella spp., was conducted on 29 clinical stool
samples that had been diagnosed with Salmonella spp. by a routine
culture technique. The entire process was achieved in a single microfluidic
chip within 35 min. In comparison to the culture reference method
that is used in the clinical laboratories, this new device performed
well in regards to the analytical parameters of sensitivity, specificity
and accuracy. Therefore, the POC device reported in this study proved
to be very appropriate for the fully integrated analysis system.
To the best of our knowledge, this is the first work to report the
sample preparation and followed by Real Time PCR (Polymerase Chain
Reaction) on a single 2.5 μl chamber chip for the detection
of Salmonella spp. bacteria in stool samples.},
doi = {10.1016/j.bios.2011.12.032},
issn = {0956-5663},
keywords = {POC device},
url = {http://www.sciencedirect.com/science/article/pii/S0956566311008542}
}
@ARTICLE{Verdu2004,
author = {Verdú, Elena F. and Bercík, Premysl and Bergonzelli, Gabriela E.
and Huang, Xian-Xi and Blennerhasset, Patricia and Rochat, Florence
and Fiaux, Muriel and Mansourian, Robert and Corthésy-Theulaz, Irène
and Collins, Stephen M.},
title = {Lactobacillus paracasei normalizes muscle hypercontractility in a
murine model of postinfective gut dysfunction},
journal = {Gastroenterology},
year = {2004},
volume = {127},
pages = {826--837},
number = {3},
month = sep,
abstract = {Background & Aims: The effects of probiotics on gut dysfunction in
postinfective irritable bowel syndrome are unknown. We tested whether
probiotics influence persistent muscle hypercontractility in mice
after recovery from infection with Trichinella spiralis and analyzed
the underlying mechanisms. Methods: Mice were gavaged with Lactobacillus
paracasei, Lactobacillus johnsonii, Bifidobacterium longum, or Bifidobacterium
lactis in spent culture medium from days 10 to 21 after infection.
Additional mice received heat-inactivated Lactobacillus paracasei,
Lactobacillus paracasei-free spent culture medium, or heat-inactivated
Lactobacillus paracasei-free spent culture medium. Lactobacilli enumeration,
immunohistochemistry, and cytokine detection (enzyme-linked immunosorbent
assay) were performed. Mice were also treated with Lactobacillus
paracasei or Lactobacillus paracasei-free spent culture medium from
days 18 to 28 after infection. Contractility was measured on days
21 and 28 after infection. Results: Lactobacillus paracasei, but
not Lactobacillus johnsonii, Bifidobacterium lactis, or Bifidobacterium
longum, attenuated muscle hypercontractility. This was associated
with a reduction in the Trichinella spiralis-associated T-helper
2 response and a reduction in transforming growth factor-[beta]1,
cyclooxygenase-2, and prostaglandin E2 levels in muscle. Attenuation
of muscle hypercontractility by Lactobacillus paracasei-free spent
culture medium was abolished after heat treatment. Improvement of
muscle hypercontractility at day 28 after infection was also observed
after the administration ofLactobacillus paracasei or Lactobacillus
paracasei-free spent culture medium from day 18 after infection.
Conclusions: Probiotics show strain-dependent attenuation of muscle
hypercontractility in an animal model of postinfective irritable
bowel syndrome. This likely occurs via both a modulation of the immunologic
response to infection and a direct effect of Lactobacillus paracasei
or a heat-labile metabolite on postinfective muscle hypercontractility.
Lactobacillus paracasei may be useful in the treatment of postinfective
irritable bowel syndrome.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4D97N0K-13/2/83f8bae647c8f35cd04ab223a6a75b18}
}
@ARTICLE{Verelst2007,
author = {Verelst, Wim and Twell, David and de Folter, Stefan and Immink, Richard
and Saedler, Heinz and Münster, Thomas},
title = {MADS-complexes regulate transcriptome dynamics during pollen maturation},
journal = {Genome Biology},
year = {2007},
volume = {8},
pages = {R249},
number = {11},
abstract = {BACKGROUND:Differentiation processes are responsible for the diversity
and functional specialization of the cell types that compose an organism.
The outcome of these processes can be studied at molecular, physiologic,
and biochemical levels by comparing different cell types, but the
complexity and dynamics of the regulatory processes that specify
the differentiation are largely unexplored.RESULTS:Here we identified
the pollen-specific MIKC* class of MADS-domain transcription factors
as major regulators of transcriptome dynamics during male reproductive
cell development in Arabidopsis thaliana. Pollen transcript profiling
of mutants deficient in different MIKC* protein complexes revealed
that they control a transcriptional switch that directs pollen maturation
and that is essential for pollen competitive ability. We resolved
the functional redundancy among the MIKC* proteins and uncovered
part of the underlying network by identifying the non-MIKC* MADS-box
genes AGL18 and AGL29 as downstream regulators of a subset of the
MIKC* MADS-controlled genes.CONCLUSION:Our results provide a first,
unique, and compelling insight into the complexity of a transcription
factor network that directs cellular differentiation during pollen
maturation, a process that is essential for male reproductive fitness
in flowering plants.},
doi = {10.1186/gb-2007-8-11-r249},
issn = {1465-6906},
owner = {Meike Kuschel},
pubmedid = {18034896},
timestamp = {2010.04.07},
url = {http://genomebiology.com/content/8/11/R249}
}
@ARTICLE{Vergnolle2005,
author = {Vergnolle, Chantal and Vaultier, Marie-Noelle and Taconnat, Ludivine
and Renou, Jean-Pierre and Kader, Jean-Claude and Zachowski, Alain
and Ruelland, Eric},
title = {The Cold-Induced Early Activation of Phospholipase C and D Pathways
Determines the Response of Two Distinct Clusters of Genes in Arabidopsis
Cell Suspensions},
journal = {Plant Physiology},
year = {2005},
volume = {139},
pages = {1217--1233},
number = {3},
month = nov,
abstract = {In plants, a temperature downshift represents a major stress that
will lead to the induction or repression of many genes. Therefore,
the cold signal has to be perceived and transmitted to the nucleus.
In response to a cold exposure, we have shown that the phospholipase
D (PLD) and the phospholipase C (PLC)/diacylglycerol kinase pathways
are simultaneously activated. The role of these pathways in the cold
response has been investigated by analyzing the transcriptome of
cold-treated Arabidopsis (Arabidopsis thaliana) suspension cells
in the presence of U73122 or ethanol, inhibitors of the PLC/diacylglycerol
kinase pathway and of the phosphatidic acid produced by PLD, respectively.
This approach showed that the expression of many genes was modified
by the cold response in the presence of such agents. The cold responses
of most of the genes were repressed, thus correlating with the inhibitory
effect of U73122 or ethanol. We were thus able to identify 58 genes
that were regulated by temperature downshift via PLC activity and
87 genes regulated by temperature downshift via PLD-produced phosphatidic
acid. Interestingly, each inhibitor appeared to affect different
cold response genes. These results support the idea that both the
PLC and PLD pathways are upstream of two different signaling pathways
that lead to the activation of the cold response. The connection
of these pathways with the CBF pathway, currently the most understood
genetic system playing a role in cold acclimation, is discussed.},
url = {http://www.plantphysiol.org/cgi/content/abstract/139/3/1217}
}
@ARTICLE{Vergoz2009,
author = {Vergoz, Vanina and McQuillan, H. James and Geddes, Lisa H. and Pullar,
Kiri and Nicholson, Brad J. and Paulin, Michael G. and Mercer, Alison
R.},
title = {Peripheral modulation of worker bee responses to queen mandibular
pheromone},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {20930--20935},
number = {49},
month = dec,
abstract = {It is generally accepted that young worker bees (Apis mellifera L.)
are highly attracted to queen mandibular pheromone (QMP). Our results
challenge this widely held view. We have found that unless young
workers are exposed to QMP early in adult life, they, like foragers,
avoid contact with this pheromone. Our data indicate that responses
to QMP are regulated peripherally, at the level of the antennal sensory
neurons, and that a window of opportunity exists in which QMP can
alter a young bee's response to this critically important pheromone.
Exposing young bees to QMP from the time of adult emergence reduces
expression in the antennae of the D1-like dopamine receptor gene,
Amdop1. Levels of Amdop3 transcript, on the other hand, and of the
octopamine receptor gene Amoa1, are significantly higher in the antennae
of bees strongly attracted to QMP than in bees showing no attraction
to this pheromone. A decline in QMP attraction with age is accompanied
by a fall in expression in worker antennae of the D2-like dopamine
receptor, AmDOP3, a receptor that is selectively activated by QMP.
Taken together, our findings suggest that QMP's actions peripherally
not only suppress avoidance behavior, but also enhance attraction
to QMP, thereby facilitating attendance of the queen.},
url = {http://www.pnas.org/cgi/content/abstract/106/49/20930}
}
@ARTICLE{Verhofstad2010,
author = {Verhofstad, Nicole and Pennings, Jeroen and van Oostrom, Conny and
van Benthem, Jan and van Schooten, Frederik and van Steeg, Harry
and Godschalk, Roger},
title = {Benzo(a)pyrene induces similar gene expression changes in testis
of DNA repair proficient and deficient mice},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {333},
number = {1},
abstract = {BACKGROUND:Benzo [a]pyrene (B[a]P) exposure induces DNA adducts at
all stages of spermatogenesis and in testis, and removal of these
lesions is less efficient in nucleotide excision repair deficient
Xpc-/- mice than in wild type mice. In this study, we investigated
by using microarray technology whether compromised DNA repair in
Xpc-/- mice may lead to a transcriptional reaction of the testis
to cope with increased levels of B[a]P induced DNA damage.RESULTS:Two-Way
ANOVA revealed only 4 genes differentially expressed between wild
type and Xpc-/- mice, and 984 genes between testes of B[a]P treated
and untreated mice irrespective of the mouse genotype. However, the
level in which these B[a]P regulated genes are expressed differs
between Wt and Xpc-/- mice (p = 0.000000141), and were predominantly
involved in the regulation of cell cycle, translation, chromatin
structure and spermatogenesis, indicating a general stress response.
In addition, analysis of cell cycle phase dependent gene expression
revealed that expression of genes involved in G1-S and G2-M phase
arrest was increased after B[a]P exposure in both genotypes. A slightly
higher induction of average gene expression was observed at the G2-M
checkpoint in Xpc-/- mice, but this did not reach statistical significance
(P = 0.086). Other processes that were expected to have changed by
exposure, like apoptosis and DNA repair, were not found to be modulated
at the level of gene expression.CONCLUSION:Gene expression in testis
of untreated Xpc-/- and wild type mice were very similar, with only
4 genes differentially expressed. Exposure to benzo(a)pyrene affected
the expression of genes that are involved in cell cycle regulation
in both genotypes, indicating that the presence of unrepaired DNA
damage in testis blocks cell proliferation to protect DNA integrity
in both DNA repair proficient and deficient animals.},
doi = {10.1186/1471-2164-11-333},
issn = {1471-2164},
pubmedid = {20504355},
url = {http://www.biomedcentral.com/1471-2164/11/333}
}
@ARTICLE{Verlaan2009,
author = {Verlaan, Dominique J. and Berlivet, Soizik and Hunninghake, Gary
M. and Madore, Anne-Marie and Larivière, Mathieu and Moussette, Sanny
and Grundberg, Elin and Kwan, Tony and Ouimet, Manon and Ge, Bing
and Hoberman, Rose and Swiatek, Marcin and Dias, Joana and Lam, Kevin
C.L. and Koka, Vonda and Harmsen, Eef and Soto-Quiros, Manuel and
Avila, Lydiana and Celedón, Juan C. and Weiss, Scott T. and Dewar,
Ken and Sinnett, Daniel and Laprise, Catherine and Raby, Benjamin
A. and Pastinen, Tomi and Naumova, Anna K.},
title = {Allele-Specific Chromatin Remodeling in the ZPBP2/GSDMB/ORMDL3 Locus
Associated with the Risk of Asthma and Autoimmune Disease},
journal = {The American Journal of Human Genetics},
year = {2009},
volume = {85},
pages = {377--393},
number = {3},
month = sep,
abstract = {Common SNPs in the chromosome 17q12-q21 region alter the risk for
asthma, type 1 diabetes, primary biliary cirrhosis, and Crohn disease.
Previous reports by us and others have linked the disease-associated
genetic variants with changes in expression of GSDMB and ORMDL3 transcripts
in human lymphoblastoid cell lines (LCLs). The variants also alter
regulation of other transcripts, and this domain-wide cis-regulatory
effect suggests a mechanism involving long-range chromatin interactions.
Here, we further dissect the disease-linked haplotype and identify
putative causal DNA variants via a combination of genetic and functional
analyses. First, high-throughput resequencing of the region and genotyping
of potential candidate variants were performed. Next, additional
mapping of allelic expression differences in Yoruba HapMap LCLs allowed
us to fine-map the basis of the cis-regulatory differences to a handful
of candidate functional variants. Functional assays identified allele-specific
differences in nucleosome distribution, an allele-specific association
with the insulator protein CTCF, as well as a weak promoter activity
for rs12936231. Overall, this study shows a common disease allele
linked to changes in CTCF binding and nucleosome occupancy leading
to altered domain-wide cis-regulation. Finally, a strong association
between asthma and cis-regulatory haplotypes was observed in three
independent family-based cohorts (p = 1.78 × 10-8). This study demonstrates
the requirement of multiple parallel allele-specific tools for the
investigation of noncoding disease variants and functional fine-mapping
of human disease-associated haplotypes.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4X4Y6B0-5/2/0f3f916c124c3d4c4aee98fed0805449}
}
@ARTICLE{Verma2010,
author = {Verma, Subhash and Goldammer, Tom and Aitken, Robert},
title = {Cloning and expression of activation induced cytidine deaminase from
Bos taurus},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {134},
pages = {151--159},
number = {3-4},
month = apr,
issn = {0165-2427},
keywords = {AID},
url = {http://www.sciencedirect.com/science/article/B6TD5-4X4GHPC-1/2/19be6174e91a8373e0fa69b9f951e848}
}
@ARTICLE{Verma2006,
author = {Verma, Saguna and Ziegler, Katja and Ananthula, Praveen and Co, Juliene
K.G. and Frisque, Richard J. and Yanagihara, Richard and Nerurkar,
Vivek R.},
title = {JC virus induces altered patterns of cellular gene expression: Interferon-inducible
genes as major transcriptional targets},
journal = {Virology},
year = {2006},
volume = {345},
pages = {457--467},
number = {2},
month = feb,
abstract = {Human polyomavirus JC (JCV) infects 80% of the population worldwide.
Primary infection, typically occurring during childhood, is asymptomatic
in immunocompetent individuals and results in lifelong latency and
persistent infection. However, among the severely immunocompromised,
JCV may cause a fatal demyelinating disease, progressive multifocal
leukoencephalopathy (PML). Virus-host interactions influencing persistence
and pathogenicity are not well understood, although significant regulation
of JCV activity is thought to occur at the level of transcription.
Regulation of the JCV early and late promoters during the lytic cycle
is a complex event that requires participation of both viral and
cellular factors. We have used cDNA microarray technology to analyze
global alterations in gene expression in JCV-permissive primary human
fetal glial cells (PHFG). Expression of more than 400 cellular genes
was altered, including many that influence cell proliferation, cell
communication and interferon (IFN)-mediated host defense responses.
Genes in the latter category included signal transducer and activator
of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56),
myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS),
and cig5. The expression of these genes was further confirmed in
JCV-infected PHFG cells and the human glioblastoma cell line U87MG
to ensure the specificity of JCV in inducing this strong antiviral
response. Results obtained by real-time RT-PCR and Western blot analyses
supported the microarray data and provide temporal information related
to virus-induced changes in the IFN response pathway. Our data indicate
that the induction of an antiviral response may be one of the cellular
factors regulating/controlling JCV replication in immunocompetent
hosts and therefore constraining the development of PML.},
issn = {0042-6822},
keywords = {Polyomavirus, JCV, PML, Interferon stimulating genes, cig5, MxA, U87MG,
Primary human fetal glial cells, Transfection, Infection, Microarray,
Real-time PCR, Copy numbers, Chimeras, JCV-SV40 chimera, Mad1/SVEDelta},
url = {http://www.sciencedirect.com/science/article/B6WXR-4HKCYPX-5/2/a846050e778797606aff48983e789091}
}
@ARTICLE{Vermijlen2010,
author = {Vermijlen, David and Brouwer, Margreet and Donner, Catherine and
Liesnard, Corinne and Tackoen, Marie and Van Rysselberge, Michel
and Twite, Nicolas and Goldman, Michel and Marchant, Arnaud and Willems,
Fabienne},
title = {Human cytomegalovirus elicits fetal {gamma}{delta} T cell responses
in utero},
journal = {J. Exp. Med.},
year = {2010},
volume = {207},
pages = {807--821},
number = {4},
month = apr,
abstract = {The fetus and infant are highly susceptible to viral infections. Several
viruses, including human cytomegalovirus (CMV), cause more severe
disease in early life compared with later life. It is generally accepted
that this is a result of the immaturity of the immune system. {gamma}{delta}
T cells are unconventional T cells that can react rapidly upon activation
and show major histocompatibility complex-unrestricted activity.
We show that upon CMV infection in utero, fetal {gamma}{delta} T
cells expand and become differentiated. The expansion was restricted
to V{gamma}9-negative {gamma}{delta} T cells, irrespective of their
V{delta} chain expression. Differentiated {gamma}{delta} T cells
expressed high levels of IFN-{gamma}, transcription factors T-bet
and eomes, natural killer receptors, and cytotoxic mediators. CMV
infection induced a striking enrichment of a public V{gamma}8V{delta}1-TCR,
containing the germline-encoded complementary-determining-region-3
(CDR3) {delta}1-CALGELGDDKLIF/CDR3{gamma}8-CATWDTTGWFKIF. Public
V{gamma}8V{delta}1-TCR-expressing cell clones produced IFN-{gamma}
upon coincubation with CMV-infected target cells in a TCR/CD3-dependent
manner and showed antiviral activity. Differentiated {gamma}{delta}
T cells and public V{gamma}8V{delta}1-TCR were detected as early
as after 21 wk of gestation. Our results indicate that functional
fetal {gamma}{delta} T cell responses can be generated during development
in utero and suggest that this T cell subset could participate in
antiviral defense in early life.},
url = {http://jem.rupress.org/cgi/content/abstract/207/4/807}
}
@ARTICLE{Vermitsky2006,
author = {Vermitsky, John-Paul and Earhart, Kelly D. and Smith, W. Lamar and
Homayouni, Ramin and Edlind, Thomas D. and Rogers, P. David},
title = {Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption
and genome-wide expression studies},
journal = {Molecular Microbiology},
year = {2006},
volume = {61},
pages = {704--722},
number = {3},
abstract = {Summary Candida glabrata emerged in the last decade as a common cause
of mucosal and invasive fungal infection, in large part due to its
intrinsic or acquired resistance to azole antifungals such as fluconazole.
In C. glabrata clinical isolates, the predominant mechanism behind
azole resistance is upregulated expression of multidrug transporter
genes CDR1 and PDH1. We previously reported that azole-resistant
mutants (MIC ≥ 64 μg ml−1) of strain 66032 (MIC = 16 μg ml−1)
similarly show coordinate CDR1-PDH1 upregulation, and in one of these
(F15) a putative gain-of-function mutation was identified in the
single homologue of Saccharomyces cerevisiae transcription factors
Pdr1–Pdr3. Here we show that disruption of C. glabrata PDR1 conferred
equivalent fluconazole hypersensitivity (MIC = 2 μg ml−1)
to both F15 and 66032 and eliminated both constitutive and fluconazole-induced
CDR1-PDH1 expression. Reintroduction of wild-type or F15 PDR1 fully
reversed these effects; together these results demonstrate a role
for this gene in both acquired and intrinsic azole resistance. CDR1
disruption had a partial effect, reducing fluconazole trailing in
both strains while restoring wild-type susceptibility (MIC = 16 μg ml−1)
to F15. In an azole-resistant clinical isolate, PDR1 disruption reduced
azole MICs eight- to 64-fold with no effect on sensitivity to other
antifungals. To extend this analysis, C. glabrata microarrays were
generated and used to analyse genome-wide expression in F15 relative
to its parent. Homologues of 10 S. cerevisiae genes previously shown
to be Pdr1–Pdr3 targets were upregulated (YOR1, RTA1, RSB1, RPN4,
YLR346c and YMR102c along with CDR1, PDH1 and PDR1 itself) or downregulated
(PDR12); roles for these genes include small molecule transport and
transcriptional regulation. However, expression of 99 additional
genes was specifically altered in C. glabrata F15; their roles include
transport (e.g. QDR2, YBT1), lipid metabolism (ATF2, ARE1), cell
stress (HSP12, CTA1), DNA repair (YIM1, MEC3) and cell wall function
(MKC7, MNT3). These azole resistance-associated changes could affect
C. glabrata tissue-specific virulence; in support of this, we detected
differences in F15 oxidant, alcohol and weak acid sensitivities.
C. glabrata provides a promising model for studying the genetic
basis of multidrug resistance and its impact on virulence.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2006.05235.x}
}
@ARTICLE{Vernal2008,
author = {Vernal, R. and Leon, R. and Herrera, D. and Garcia-Sanz, J. A. and
Silva, A. and Sanz, M.},
title = {Variability in the response of human dendritic cells stimulated with
Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans},
journal = {Journal of Periodontal Research},
year = {2008},
volume = {43},
pages = {689--697},
number = {6},
abstract = {Background and Objective:  Dendritic cells are able to prime and
polarize naïve T cells towards either a T helper 1 or a T helper
2 response, depending on the antigen type and concentration, the
costimulatory signals and the local cytokine millieu. In this investigation,
we analyzed the response of human dendritic cells to stimulation
with different concentrations of Porphyromonas gingivalis or Aggregatibacter
actinomycetemcomitans. Material and Methods:  Using different concentrations
of P. gingivalis ATCC 33277 and A. actinomycetemcomitans ATCC 33384,
we determined the expression of the maturation markers CD80 and CD86
from purified human dendritic cells by flow cytometry. We also evaluated
the mRNA expression levels for the cytokines interleukin-1β, interleukin-2,
interleukin-5, interleukin-6, interleukin-10, interleukin-12, interleukin-13,
interferon-γ, tumor necrosis factor-α and tumor necrosis factor-β
by quantitative real-time reverse transcription–polymerase chain
reaction. Results:  Both P. gingivalis and A. actinomycetemcomitans
led to dendritic cell maturation, but the expression of CD80 was
higher when the dendritic cells were stimulated with A. actinomycetemcomitans.
Although both pathogens induced a T helper 1 pattern of cytokine
expression, A. actinomycetemcomitans-stimulated dendritic cells
expressed interleukin-1β, interleukin-12, interferon-γ, tumor necrosis
factor-α and tumor necrosis factor-β at lower bacterial concentrations
than P. gingivalis. While 106 bacteria/mL of P. gingivalis or
104 bacteria/mL of A. actinomycetemcomitans induced expression
of interleukin-12p40, the expression of other cytokines required
10 to 100-fold higher concentrations of bacteria. Conclusion: 
These results demonstrate that A. actinomycetemcomitans is a more
potent immunogen than P. gingivalis because, at least in vitro,
it induces stronger differentiation and activation of dendritic cells.
In addition, our data also show that for a given strain, the bacterial
load determines the pattern of cytokines that are expressed.},
issn = {1600-0765},
keywords = {dendritic cells, cytokines, CD80, Porphyromonas gingivalis, Aggregatibacter
actinomycetemcomitans},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0765.2007.01073.x}
}
@ARTICLE{Vernal2008a,
author = {Vernal, Rolando and Velásquez, Edgar and Gamonal, Jorge and Garcia-Sanz,
Jose A. and Silva, Augusto and Sanz, Mariano},
title = {Expression of proinflammatory cytokines in osteoarthritis of the
temporomandibular joint},
journal = {Archives of Oral Biology},
year = {2008},
volume = {53},
pages = {910--915},
number = {10},
month = oct,
issn = {0003-9969},
keywords = {Temporomandibular joint, Temporomandibular disorders, Osteoarthritis,
Cytokines, Inflammation, TMJ, OA, IL10, IL12, IL17},
url = {http://www.sciencedirect.com/science/article/B6T4J-4SM209B-1/2/7b462560ad2cea181a4d21cc51304bd9}
}
@ARTICLE{Vernet2004,
author = {Vernet, Guy},
title = {Molecular diagnostics in virology},
journal = {Journal of Clinical Virology},
year = {2004},
volume = {31},
pages = {239--247},
number = {4},
month = dec,
abstract = {Molecular biology has significantly improved diagnosis in the field
of clinical virology. Virus discovery and rapid implementation of
diagnostic tests for newly discovered viruses has strongly beneficiated
from the development of molecular techniques. Viral load and antiviral
resistance or subtyping assays are now part of the biological monitoring
of patients chronically infected by human immunodeficiency virus
(HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV.
It will be important to add to this panel assays for other viruses
of the herpesviridae family. Qualitative assays for the detection
of blood-borne viruses have increased safety of blood donation and
organ transplantation. Screening of other blood-borne viruses (parvovirus
B19, HAV), multiplexing of detection and test automation to improve
practicability and reduce costs will be the next steps. A major evolution
in the near future will be the generalization of NAT for the diagnosis
of viral etiology in patients, mostly with respiratory, CNS or gastro-intestinal
diseases. Major technical improvements have been made to avoid obstacles
that still limit this generalization, i.e. genetic variability of
viruses, multiplex detection, contamination risk. Commercial offers
already exist but menus must be extended to limit the validation
and documentation work associated with home-brew assays. Real-time
amplification has allowed the development of new NAT platforms but
automation and integration of all steps of the reaction are still
required to reduce hands-on-time, time-to-result and costs, and to
increase throughput.},
issn = {1386-6532},
keywords = {Virology, Diagnostics, Nucleic acid tests},
url = {http://www.sciencedirect.com/science/article/B6VJV-4D4R674-1/2/1bccf7b9e231e18679987805ce24b7dc}
}
@ARTICLE{Vernet2011,
author = {Vernet, G. and Saha, S. and Satzke, C. and Burgess, D. H. and Alderson,
M. and Maisonneuve, J.-F. and Beall, B. W. and Steinhoff, M. C. and
Klugman, K. P.},
title = {Laboratory-based diagnosis of pneumococcal pneumonia: state of the
art and unmet needs},
journal = {Clinical Microbiology and Infection},
year = {2011},
volume = {17},
pages = {1--13},
abstract = {Clin Microbiol Infect 2011; 17: (Suppl. 3) 1–13AbstractIn view of
the increasing use of pneumococcal vaccines, especially in the developing
world, there is a need for appropriate diagnostics to understand
the aetiology of pneumonia, to define the burden of pneumococcal
disease, and to monitor vaccine efficacy and effectiveness. This
article summarizes a meeting on the diagnosis, detection and serotyping
of pneumococcal disease organized by PATH and Fondation Mérieux
(18–20 October 2009, Fondation Mérieux Conference Centre, Les
Pensières, France). Workers and experts met to discuss the gaps
in the microbiology-based diagnosis of Streptococcus pneumoniae disease,
with special emphasis on pneumonia. The meeting was designed to evaluate
the state of the art of pneumococcal diagnostics and serotyping methodologies,
identify research and development needs, and propose new guidelines
to public health authorities to support the introduction of vaccines.
Regarding detection, the main recommendations were to encourage chest
X-rays and antigen detection in urine. Large-scale studies are needed
to evaluate the diagnostic utility of test algorithms that associate
chest X-rays, antigen detection in urine, S. pneumoniae quantitative
PCR in nasopharyngeal aspirates and sputum, and C-reactive protein
or procalcitonin measurement in blood. Efforts should be focused
on proteomics to identify pneumococcus-specific antigens in urine
or host markers in blood expressed during pneumonia. It was recommended
to develop S. pneumoniae typing capacities, to understand the epidemiology
of pneumococcal disease, and to evaluate vaccine effectiveness. Simple
and effective approaches are encouraged, and new technologies based
on beads, microarrays or deep sequencing should be developed to determine,
in a single test capsular serotype, resistance profile and genotype.},
doi = {10.1111/j.1469-0691.2011.03496.x},
issn = {1469-0691},
keywords = {Pneumococcal pneumonia, diagnosis, pneumococci, detection, serotyping},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-0691.2011.03496.x}
}
@ARTICLE{Vernie2008,
author = {Vernie, Tatiana and Moreau, Sandra and de Billy, Francoise and Plet,
Julie and Combier, Jean-Philippe and Rogers, Christian and Oldroyd,
Giles and Frugier, Florian and Niebel, Andreas and Gamas, Pascal},
title = {EFD Is an ERF Transcription Factor Involved in the Control of Nodule
Number and Differentiation in Medicago truncatula},
journal = {PLANT CELL},
year = {2008},
volume = {20},
pages = {2696--2713},
number = {10},
month = oct,
abstract = {Mechanisms regulating legume root nodule development are still poorly
understood, and very few regulatory genes have been cloned and characterized.
Here, we describe EFD (for ethylene response factor required for
nodule differentiation), a gene that is upregulated during nodulation
in Medicago truncatula. The EFD transcription factor belongs to the
ethylene response factor (ERF) group V, which contains ERN1, 2, and
3, three ERFs involved in Nod factor signaling. The role of EFD in
the regulation of nodulation was examined through the characterization
of a null deletion mutant (efd-1), RNA interference, and overexpression
studies. These studies revealed that EFD is a negative regulator
of root nodulation and infection by Rhizobium and that EFD is required
for the formation of functional nitrogen-fixing nodules. EFD appears
to be involved in the plant and bacteroid differentiation processes
taking place beneath the nodule meristem. We also showed that EFD
activated Mt RR4, a cytokinin primary response gene that encodes
a type-A response regulator. We propose that EFD induction of Mt
RR4 leads to the inhibition of cytokinin signaling, with two consequences:
the suppression of new nodule initiation and the activation of differentiation
as cells leave the nodule meristem. Our work thus reveals a key regulator
linking early and late stages of nodulation and suggests that the
regulation of the cytokinin pathway is important both for nodule
initiation and development.},
url = {http://www.plantcell.org/cgi/content/abstract/20/10/2696}
}
@ARTICLE{Veroni2010,
author = {Veroni, Caterina and Gabriele, Lucia and Canini, Irene and Castiello,
Luciano and Coccia, Eliana and Remoli, Maria Elena and Columba-Cabezas,
Sandra and Aricò, Eleonora and Aloisi, Francesca and Agresti, Cristina},
title = {Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory
pathways},
journal = {Molecular and Cellular Neuroscience},
year = {2010},
volume = {45},
pages = {234--244},
number = {3},
month = nov,
abstract = {Fine regulation of the innate immune response following brain injury
or infection is important to avoid excessive activation of microglia
and its detrimental consequences on neural cell viability and function.
To get insights on the molecular networks regulating microglia activation,
we analyzed expression, regulation and functional relevance of tumor
necrosis factor receptors (TNFR) 2 in cultured mouse microglia. We
found that microglia upregulate TNFR2 mRNA and protein and shed large
amounts of soluble TNFR2, but not TNFR1, in response to pro-inflammatory
stimuli and through activation of TNFR2 itself. By microarray analysis,
we demonstrate that TNFR2 stimulation in microglia regulates expression
of genes involved in immune processes, including molecules with anti-inflammatory
and neuroprotective function like granulocyte colony-stimulating
factor, adrenomedullin and IL-10. In addition, we identify IFN-[gamma]
as a regulator of the balance between pro- and anti-inflammatory/neuroprotective
factors induced by TNFR2 stimulation. These data indicate that, through
TNFR2, microglia may contribute to the counter-regulatory response
activated in neuropathological conditions.},
issn = {1044-7431},
keywords = {Glial cells, Inflammation, Cytokines, Cytokine receptors, Microarrays},
url = {http://www.sciencedirect.com/science/article/B6WNB-50DF8CP-2/2/cc6bba8c70f5234125280d91a9c65f18}
}
@ARTICLE{Verpoorte2002,
author = {Verpoorte, Elisabeth},
title = {Microfluidic chips for clinical and forensic analysis},
journal = {ELECTROPHORESIS},
year = {2002},
volume = {23},
pages = {677--712},
number = {5},
abstract = {Abstract 10.1002/1522-2683(200203)23:5<677::AID-ELPS677>3.3.CO;2-#
This review gives an overview of developments in the field of microchip
analysis for clinical diagnostic and forensic applications. The approach
chosen to review the literature is different from that in most microchip
reviews to date, in that the information is presented in terms of
analytes tested rather than microchip method. Analyte categories
for which examples are presented include (i) drugs (quality control,
seizures) and explosives residues, (ii) drugs and endogenous small
molecules and ions in biofluids, (iii) proteins and peptides, and
(iv) analysis of nucleic acids and oligonucleotides. Few cases of
microchip analysis of physiological samples or other “real-world�
matrices were found. However, many of the examples presented have
potential application for these samples, especially with ongoing
parallel developments involving integration of sample pretreatment
onto chips and the use of fluid propulsion mechanisms other than
electrokinetic pumping.},
issn = {1522-2683},
keywords = {Clinical analysis, Forensic analysis, Microfluidic chips, Review},
publisher = {WILEY-VCH Verlag GmbH},
url = {http://dx.doi.org/10.1002/1522-2683(200203)23:5<677::AID-ELPS677>3.0.CO;2-8}
}
@ARTICLE{Verret2011a,
author = {Verret, Valentin and Bevilacqua, Claudia and Schwartz-Cornil, Isabelle
and Pelage, Jean-Pierre and Wassef, Michel and Namur, Julien and
Bédouet, Laurent and Lewis, Andrew L. and Martin, Patrice and Laurent,
Alexandre},
title = {IL6 and TNF expression in vessels and surrounding tissues after embolization
with ibuprofen-loaded beads confirms diffusion of ibuprofen},
journal = {European Journal of Pharmaceutical Sciences},
year = {2011},
volume = {42},
pages = {489--495},
number = {5},
month = apr,
abstract = {Purpose In the treatment of uterine fibroid embolization related pain,
the use of embolics loaded with non-steroidal anti-inflammatory drugs
(NSAID) relies on an efficient delivery and impregnation of the embolized
tissue. Immuno-labelling and spectroscopic techniques have demonstrated
the release of ibuprofen from drug eluting beads ([Wassef et al.,
2008] and [Namur et al., 2009]) but failed to demonstrate diffusion
of the drug beyond the vascular wall (VW). We investigated whether
ibuprofen diffused beyond the VW in surrounding tissues (ST), by
tracking its biological effects through the modulation of expression
of two main inflammatory cytokines.Materials and methods Uterine
arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB)
or non-loaded beads (BB) and sacrificed at one week. On frozen tissue
slices, VWs of occluded arteries were isolated from ST using laser
capture microdissection. RNA was extracted from VW and ST samples.
Gene expression of IL6 and TNF[alpha] genes was measured by quantitative
real-time PCR (qPCR).Results IL6 expression was significantly increased
in IBU-BB compared to BB group both in VW (VW: fold-change (FC) = 4.9,
p = 0.0009) and ST (ST: FC = 8.7, p = 0.0003). In IBU-BB, IL6 was
significantly more expressed in VW than in ST (FC = 4.4; p = 0.0009).
TNF[alpha] expression was not significantly different between IBU-BB
and BB groups.Conclusion Using qPCR + microdissection was useful
to evaluate the spread of the biological effects of drug-loaded systems
which attest of the tissular release. This approach can be considered
when other drug detection techniques are unsuccessful or difficult
to achieve. IL6 can be used as a marker of ibuprofen released by
drug eluting beads in uterus. Gradient of expression of IL6 suggests
diffusion of ibuprofen across the VW into the ST.},
issn = {0928-0987},
keywords = {Embolization, Drug-delivery, Ibuprofen, Quantitative-PCR, IL6},
url = {http://www.sciencedirect.com/science/article/pii/S0928098711000340}
}
@ARTICLE{Verret2011,
author = {Verret, Valentin and Wassef, Michel and Pelage, Jean-Pierre and Ghegediban,
Saïda H. and Jouneau, Luc and Moine, Laurence and Labarre, Denis
and Golzarian, Jafar and Schwartz-Cornil, Isabelle and Laurent, Alexandre},
title = {Influence of degradation on inflammatory profile of polyphosphazene
coated PMMA and trisacryl gelatin microspheres in a sheep uterine
artery embolization model},
journal = {Biomaterials},
year = {2011},
volume = {32},
pages = {339--351},
number = {2},
month = jan,
abstract = {Embolization with microspheres is widely applied to treat uterine
fibroids. However, the foreign body reaction that could result from
the degradation of the microspheres remains to be evaluated to adequately
appreciate the tissular tolerance to such biomaterials. We compared
herein the in situ degradation of PMMA microspheres coated with polyphosphazene
(PMMA-PPms) and trisacryl gelatin microspheres (TGms) and we thoroughly
investigated the induced local inflammatory responses, at 1 and 4
weeks after uterine artery embolization in sheep, by using immunohistochemistry
and microarray analyses. PMMA-PPms underwent an acute and partial
degradation that was associated with the early recruitment of phagocytic
cells (CD172a+ and MHCII+), and with the up-regulated expression
of genes involved in the movement of phagocytes (ALOX5AP, CXCL2,
CXCL5, IL8, PTGS2, YARS). By contrast, TGms were not degraded and
triggered a different inflammation profile including the recruitment
of FBR Giant Cells and T-lymphocytes (CD4+) and the increased expression
of genes involved in lymphocyte activation (CXCL10, IL2RG, IRAK4,
MALT1). Our results indicate that, in contrast to a non-degradable
microsphere such as TGms which is associated to a poorly inflammatory
foreign body reaction that rapidly resolves, PMMA-PPms, which is
partially degradable, rapidly recruits and activates inflammatory
phagocytes, thus delaying the resolution of the foreign body reaction.},
issn = {0142-9612},
keywords = {Embolization, Inflammation, Foreign body response, Degradation, Gene
expression},
url = {http://www.sciencedirect.com/science/article/pii/S014296121001152X}
}
@ARTICLE{Verrier2009,
author = {Verrier, Jonathan D. and Lau, Pierre and Hudson, Lynn and Murashov,
Alexander K. and Renne, Rolf and Notterpek, Lucia},
title = {Peripheral myelin protein 22 is regulated post-transcriptionally
by miRNA-29a},
journal = {Glia},
year = {2009},
volume = {57},
pages = {1265--1279},
number = {12},
abstract = {Abstract 10.1002/glia.20846.abs Peripheral myelin protein 22 (PMP22)
is a dose-sensitive, disease-associated protein primarily expressed
in myelinating Schwann cells. Either reduction or overproduction
of PMP22 can result in hereditary neuropathy, suggesting a requirement
for correct protein expression for peripheral nerve biology. PMP22
is post-transcriptionally regulated and the 3′untranslated region
(3′UTR) of the gene exerts a negative effect on translation. MicroRNAs
(miRNAs) are small regulatory molecules that function at a post-transcriptional
level by targeting the 3′UTR in a reverse complementary manner.
We used cultured Schwann cells to demonstrate that alterations in
the miRNA biogenesis pathway affect PMP22 levels, and endogenous
PMP22 is subjected to miRNA regulation. GW-body formation, the proposed
cytoplasmic site for miRNA-mediated repression, and Dicer expression,
an RNase III family ribonuclease involved in miRNA biogenesis, are
co-regulated with the differentiation state of Schwann cells. Furthermore,
the levels of Dicer inversely correlate with PMP22, while the inhibition
of Dicer leads to elevated PMP22. Microarray analysis of actively
proliferating and differentiated Schwann cells, in conjunction with
bioinformatics programs, identified several candidate PMP22-targeting
miRNAs. Here we demonstrate that miR-29a binds and inhibits PMP22
reporter expression through a specific miRNA seed binding region.
Over-expression of miR-29a enhances the association of PMP22 RNA
with Argonaute 2, a protein involved in miRNA function, and reduces
the steady-state levels of PMP22. In contrast, inhibition of endogenous
miR-29a relieves the miRNA-mediated repression of PMP22. Correlation
analyses of miR-29 and PMP22 in sciatic nerves reveal an inverse
relationship, both developmentally and in post-crush injury. These
results identify PMP22 as a target of miRNAs and suggest that myelin
gene expression by Schwann cells is regulated by miRNAs. © 2009
Wiley-Liss, Inc.},
issn = {1098-1136},
keywords = {Schwann cell, myelin, microRNA, gene regulation, myelination},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.20846}
}
@ARTICLE{Verschoor2010,
author = {Verschoor, Chris P. and Pant, Sameer D. and You, Qiumei and Kelton,
David F. and Karrow, Niel A.},
title = {Gene expression profiling of PBMCs from Holstein and Jersey cows
sub-clinically infected with Mycobacterium avium ssp. paratuberculosis},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {137},
pages = {1--11},
number = {1-2},
month = sep,
abstract = {Infection of calves with intracellular Mycobacterium avium ssp. paratuberculosis
(MAP) commonly results in a granulomatous, chronic inflammatory bowel
disease known as Johne's disease. The asymptomatic stage of this
infection can persist for the entire production life of an adult
cow, resulting in reduced performance and premature culling, as well
as transmission of MAP to progeny and herd-mates. It has been previously
shown that the gene expression profiles of peripheral blood mononuclear
cells (PBMCs) of healthy cows, and those chronically infected with
MAP are inherently different, and that these changes may be indicative
of disease progression. Since resistance to MAP infection is a heritable
trait, and has been proposed to differ amongst domestic dairy cattle
breeds, the objective of the present study was to compare gene expression
profiles of PBMCs from healthy adult Holstein and Jersey cows to
those considered to be sub-clinically infected with MAP, as indicated
by serum ELISA. Microarray analysis using a platform containing more
than 10,000 probes and ontological analysis identified differences
in gene expression between a) healthy and infected cows, including
genes involved in the inflammatory response, and calcium binding,
and b) infected Holsteins and Jerseys, including genes involved in
the immune response, and antigen processing and presentation. These
results suggest a mixed pro- and anti-inflammatory phenotype of PBMCs
from MAP-infected as compared to healthy control animals, and inherently
different levels of immune and inflammatory-related gene expression
between MAP-infected Holsteins and Jerseys.},
issn = {0165-2427},
keywords = {Paratuberculosis, Johne's disease, Microarray, Breed differences,
Ontology},
url = {http://www.sciencedirect.com/science/article/B6TD5-4YTN3V2-1/2/2b3844707c73667e8ab642b2d622a0c0}
}
@ARTICLE{Verteuil2010,
author = {de Verteuil, Danielle and Muratore-Schroeder, Tara L. and Granados,
Diana P. and Fortier, Marie-Helene and Hardy, Marie-Pierre and Bramoulle,
Alexandre and Caron, Etienne and Vincent, Krystel and Mader, Sylvie
and Lemieux, Sebastien and Thibault, Pierre and Perreault, Claude},
title = {Deletion of Immunoproteasome Subunits Imprints on the Transcriptome
and Has a Broad Impact on Peptides Presented by Major Histocompatibility
Complex I molecules},
journal = {Mol. Cell. Proteomics},
year = {2010},
volume = {9},
pages = {2034--2047},
number = {9},
month = sep,
abstract = {Proteasome-mediated proteolysis plays a crucial role in many basic
cellular processes. In addition to constitutive proteasomes (CPs),
which are found in all eukaryotes, jawed vertebrates also express
immunoproteasomes (IPs). Evidence suggests that the key role of IPs
may hinge on their impact on the repertoire of peptides associated
to major histocompatibility complex (MHC) I molecules. Using a label-free
quantitative proteomics approach, we identified 417 peptides presented
by MHC I molecules on primary mouse dendritic cells (DCs). By comparing
MHC I-associated peptides (MIPs) eluted from primary DCs and thymocytes,
we found that the MIP repertoire concealed a cell type-specific signature
correlating with cell function. Notably, mass spectrometry analyses
of DCs expressing or not IP subunits MECL1 and LMP7 showed that IPs
substantially increase the abundance and diversity of MIPs. Bioinformatic
analyses provided evidence that proteasomes harboring LMP7 and MECL1
have specific cleavage preferences and recognize unstructured protein
regions. Moreover, while differences in MIP repertoire cannot be
attributed to potential effects of IPs on gene transcription, IP
subunits deficiency altered mRNA levels of a set of genes controlling
DC function. Regulated genes segregated in clusters that were enriched
in chromosomes 4 and 8. Our peptidomic studies performed on untransfected
primary cells provide a detailed account of the MHC I-associated
immune self. This work uncovers the dramatic impact of IP subunits
MECL1 and LMP7 on the MIP repertoire and their non-redundant influence
on expression of immune-related genes.},
url = {http://www.mcponline.org/cgi/content/abstract/9/9/2034}
}
@ARTICLE{Very2007,
author = {Very, Nicole M. and Sheridan, Mark A.},
title = {Somatostatin regulates hepatic growth hormone sensitivity by internalizing
growth hormone receptors and by decreasing transcription of growth
hormone receptor mRNAs},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {292},
pages = {R1956--1962},
number = {5},
month = may,
abstract = {Somatostatins (SSs), a diverse family of peptide hormones, have been
shown to inhibit the release of growth hormone (GH) from the pituitary.
In this study, we used rainbow trout to determine whether or not
SSs affect growth in an extrapituitary manner, in particular, by
decreasing GH sensitivity in liver. SS-14 significantly decreased
hepatic GH binding in fish implanted (5.8 x 10-11 mol/h) for 15 days
and in isolated hepatocytes. The processing of 125I-labeled trout
GH (tGH) by isolated hepatocytes was investigated to determine whether
or not the decrease in GH binding capacity resulted from receptor
internalization. The internalization of 125I-labeled tGH was time
dependent. By 6 h, 100 ng/ml SS-14 increased internalization of 125I-labeled
tGH 58% over that observed in controls. Steady-state levels of mRNAs
encoding the two hepatic growth hormone receptors (GHRs) of trout,
GHR 1 and GHR 2, were measured to determine whether or not decreased
GH binding capacity also resulted from decreased GHR synthesis. SS-14
directly inhibited steady-state levels of GHR 1 and GHR 2 mRNA in
isolated hepatocytes in a concentration-dependent manner. The inhibitory
effects of SS-14 on steady-state levels of GHR mRNAs resulted from
reduced GHR mRNA transcription and not from altered mRNA stability.
These results indicate that SSs regulate hepatic GH sensitivity by
increasing GHR internalization and by altering GHR expression and
suggest that SSs coordinate growth at the level of the pituitary,
as well as at extrapituitary levels.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/292/5/R1956}
}
@ARTICLE{Vesala2011,
author = {Vesala, L. and Salminen, T. S. and Laiho, A. and Hoikkala, A. and
Kankare, M.},
title = {Cold tolerance and cold-induced modulation of gene expression in
two Drosophila virilis group species with different distributions},
journal = {Insect Molecular Biology},
year = {2011},
pages = {no--no},
abstract = {The importance of high and low temperature tolerance in adaptation
to changing environmental conditions has evoked new interest in modulations
in gene expression and metabolism linked with stress tolerance. We
investigated the effects of rapid cold hardening and cold acclimatization
on the chill coma recovery times of two Drosophila virilis group
species, Drosophila montana and D. virilis, with different distributions
and utilized a candidate gene approach to trace changes in their
gene expression during and after the cold treatments. The study showed
that cold acclimatization clearly decreases chill coma recovery times
in both species, whereas rapid cold hardening did not have a significant
effect. Microarray analysis revealed several genes showing expression
changes during different stages of cold response. Amongst the 219
genes studied, two genes showed rather consistent expression changes:
hsr-omega, which was up-regulated in both study species during cold
acclimatization, and Eip71CD, which was down-regulated in nearly
all of the cold treatments. In addition, 29 genes showed expression
changes that were more treatment- and/or species specific. Overall,
different stages of cold response elicited changes mainly in genes
involved in heat shock response, circadian rhythm and metabolism.},
doi = {10.1111/j.1365-2583.2011.01119.x},
issn = {1365-2583},
keywords = {DNA microarray, candidate genes, chill coma recovery, Drosophila montana,
Drosophila virilis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2583.2011.01119.x}
}
@ARTICLE{Vesper2006,
author = {Vesper, Amanda H. and Raetzman, Lori T. and Camper, Sally A.},
title = {Role of Prophet of Pit1 (PROP1) in Gonadotrope Differentiation and
Puberty},
journal = {Endocrinology},
year = {2006},
volume = {147},
pages = {1654--1663},
number = {4},
month = apr,
abstract = {The prophet of Pit1 (PROP1) gene is essential for normal gonadotropin
production in both humans and mice. Transgenic mice that overexpress
PROP1 in gonadotropes and thyrotropes have transient hypogonadotropic
hypogonadism and increased risk of pituitary adenomas. Here we report
a temporal study of pituitary gonadotrope terminal differentiation
and hypogonadism, delayed onset of puberty, and transient growth
insufficiency in the transgenic males. The Prop1 transgenic mice
recover from their abnormalities and exhibit normal size and fertility
at 3 months. The relatively normal expression pattern of GnRH receptor
(Gnrhr) suggests that the pituitary gonadotrope cell lineage is appropriately
specified, but the ability to synthesize LH and FSH is impaired by
excess PROP1. We report no obvious abnormalities in expression of
the transcription factors early growth response 1, NR5A1, GATA2,
TBX19, and NR0B1, or the TGF{beta} pathway members including activin,
inhibin, and activin receptors. Thus, overexpression of PROP1 may
influence gonadotrope development by a novel mechanism. Microarray
analysis identified the inhibitory transmembrane receptor gene Klrg1
and the protease gene Prss28 as candidates for involvement in this
process. We hypothesize that variation in PROP1 expression could
affect the growth spurt and the onset of puberty in humans.},
url = {http://endo.endojournals.org/cgi/content/abstract/147/4/1654}
}
@ARTICLE{Vessely2009,
author = {Vessely, Christina and Estey, Tia and Randolph, Theodore W. and Henderson,
Ian and Cooper, Julianne and Nayar, Rajiv and Braun, LaToya Jones
and Carpenter, John F.},
title = {Stability of a trivalent recombinant protein vaccine formulation
against botulinum neurotoxin during storage in aqueous solution},
journal = {J. Pharm. Sci.},
year = {2009},
volume = {98},
pages = {2970--2993},
number = {9},
abstract = {Abstract 10.1002/jps.21498.abs The adsorption of recombinant botulinum
neurotoxin (BoNT) protein-derived vaccine antigens to aluminum salt
adjuvants has been previously studied for the development of a trivalent
vaccine against the neurotoxins (Vessely et al., in press, J Pharm
Sci). The current paper describes an investigation of the stability
of recombinant BoNT antigens adsorbed to aluminum salt adjuvants
during storage in aqueous solution. Both chemical and physical changes
occurred during storage. Phosphate groups in the buffer exchanged
with hydroxyl groups on the adjuvant surface. The resulting changes
in solution pH and adjuvant surface chemistry promoted more favorable
electrostatic interaction between the BoNT proteins and the surface,
possibly increasing the affinity of the proteins for the surface
during storage. Fluorescence and UV spectroscopy suggested changes
to protein structure during storage, whereas differential scanning
calorimetry showed changes to thermal processes related to protein
conformation and/or surface adsorption. The consequence of the chemical
and physical changes to the proteins was a decrease in the ability
to desorb protein from the adjuvant surface during storage. Overall,
the results of this study emphasize the utility of a thorough characterization
of the interactions between protein antigens and aluminum salt adjuvants.
© 2008 Wiley-Liss, Inc. and the American Pharmacists Association
J Pharm Sci 98:2970–2993, 2009},
issn = {1520-6017},
keywords = {botulinum neurotoxin, recombinant vaccine, trivalent vaccine, stability,
aluminum salt adjuvant, competitive adsorption},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jps.21498}
}
@ARTICLE{Vessely2007,
author = {Vessely, Christina and Estey, Tia and Randolph, Theodore W. and Henderson,
Ian and Nayar, Rajiv and Carpenter, John F.},
title = {Effects of solution conditions and surface chemistry on the adsorption
of three recombinant botulinum neurotoxin antigens to aluminum salt
adjuvants},
journal = {J. Pharm. Sci.},
year = {2007},
volume = {96},
pages = {2375--2389},
number = {9},
abstract = {Abstract Botulinum neurotoxin (BoNT) is a biological warfare threat.
Protein antigens have been developed against the seven major BoNT
serotypes for the development of a recombinant protein vaccine. This
study is an evaluation of adsorption profiles for three of the recombinant
protein antigens to aluminum salt adjuvants in the development of
a trivalent vaccine against BoNT. Adsorption profiles were obtained
over a range of protein concentrations. The results document that
charge–charge interactions dominate the adsorption of antigen to
adjuvant. Optimal conditions for adsorption were determined. However,
potency studies and solution stability studies indicated the necessity
of using aluminum hydroxide adjuvant at low pH. To improve the adsorption
profiles to AlOH adjuvant, phosphate ions were introduced into the
adsorption buffers. The resulting change in the adjuvant chemistry
led to an improvement of adsorption of the BoNT antigens to aluminum
hydroxide adjuvant while maintaining potency. Competitive adsorption
profiles were also determined, and showed changes in maximum adsorption
from mixed solutions compared to adsorption from individual protein
solutions. The adsorption profiles for each protein varied due to
differences in adsorption mechanism and affinity for the adjuvant
surface. These results emphasize the importance of evaluating competitive
adsorption in the development of multivalent vaccine products. ©
2007 Wiley-Liss, Inc. and the American Pharmacists Association J
Pharm Sci 96: 2375–2389, 2007},
issn = {1520-6017},
keywords = {botulinum neurotoxin, recombinant vaccine, aluminum salt adjuvant,
competitive adsorption},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jps.20880}
}
@ARTICLE{Vestergaard2011,
author = {Vestergaard, Anna L. and Knudsen, Ulla B. and Munk, Torben and Rosbach,
Hanne and Martensen, Pia M.},
title = {Transcriptional expression of type-I interferon response genes and
stability of housekeeping genes in the human endometrium and endometriosis},
journal = {Mol. Hum. Reprod.},
year = {2011},
volume = {17},
pages = {243--254},
number = {4},
month = apr,
abstract = {Endometriosis is a painful chronic female disease defined by the presence
of endometrial tissue implants in ectopic (Ec) locations. The pathogenesis
is much debated, and type-I interferons (IFNs) could be involved.
The expression of genes of the type-I IFN response were profiled
by a specific PCR array of RNA obtained from Ec and eutopic (Eu)
endometrium collected from nine endometriosis patients and nine healthy
control women. Transcriptional expression levels of selected IFN-regulated
and housekeeping genes (HKGs) were investigated by real-time quantitative
reverse transcriptase PCR (qRT-PCR). Stably expressed HKGs for valid
normalization of transcriptional studies of endometrium and endometriosis
have not yet been published. Here, seven HKGs were evaluated for
stability using the GeNorm and NormFinder software. A normalization
factor based on HMBS, TBP and YWHAZ expression was suitable for normalization
of qRT-PCR studies of Eu versus Ec endometrium. In the endometrial
cell lines HEC1A, HEC1B, Ishikawa and RL95-2, HMBS and HPRT1 were
the most stably expressed. The IFN-specific PCR array indicated significantly
different expression of the genes BST2, COL16A1, HOXB2 and ISG20
between the endometrial tissue types. However, by correctly normalized
qRT-PCR, levels of BST2, COL16A1 and the highly type-I IFN-stimulated
genes ISG12A and 6-16 displayed insignificant variations. Conversely,
HOXB2 and ISG20 transcriptions were significantly reduced in endometriosis
lesions compared with endometrium from endometriosis patients and
healthy controls. In conclusion, appropriate HKGs for normalization
of qRT-PCR studies of endometrium and endometriosis have been identified
here. Abolished expression of ISG20 and HOX genes could be important
in endometriosis.},
comment = {10.1093/molehr/gaq100},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/17/4/243}
}
@ARTICLE{Vesterlund2011,
author = {Vesterlund, Liselotte and Jiao, Hong and Unneberg, Per and Hovatta,
Outi and Kere, Juha},
title = {The zebrafish transcriptome during early development},
journal = {BMC Developmental Biology},
year = {2011},
volume = {11},
pages = {30},
number = {1},
abstract = {BACKGROUND:The transition from fertilized egg to embryo is accompanied
by a multitude of changes in gene expression, and the transcriptional
events that underlie these processes have not yet been fully characterized.
In this study RNA-Seq is used to compare the transcription profiles
of four early developmental stages in zebrafish (Danio rerio) on
a global scale.RESULTS:An average of 79 M total reads were detected
from the different stages. Out of the total number of reads 65% -
73% reads were successfully mapped and 36% - 44% out of those were
uniquely mapped. The total number of detected unique gene transcripts
was 11187, of which 10096 were present at 1-cell stage. The largest
number of common transcripts was observed between 1-cell stage and
16-cell stage. An enrichment of gene transcripts with molecular functions
of DNA binding, protein folding and processing as well as metal ion
binding was observed with progression of development. The sequence
data (accession number ERP000635) is available at the European Nucleotide
Archive.CONCLUSION:Clustering of expression profiles shows that a
majority of the detected gene transcripts are present at steady levels,
and thus a minority of the gene transcripts clusters as increasing
or decreasing in expression over the four investigated developmental
stages. The three earliest developmental stages were similar when
comparing highly expressed genes, whereas the 50% epiboly stage differed
from the other three stages in the identity of highly expressed genes,
number of uniquely expressed genes and enrichment of GO molecular
functions. Taken together, these observations indicate a major transition
in gene regulation and transcriptional activity taking place between
the 512-cell and 50% epiboly stages, in accordance with previous
studies.},
doi = {10.1186/1471-213X-11-30},
issn = {1471-213X},
pubmedid = {21609443},
url = {http://www.biomedcentral.com/1471-213X/11/30}
}
@ARTICLE{Vetter2007,
author = {Vetter, Douglas E. and Katz, Eleonora and Maison, Stephane F. and
Taranda, Julian and Turcan, Sevin and Ballestero, Jimena and Liberman,
M. Charles and Elgoyhen, A. Belen and Boulter, Jim},
title = {The {alpha}10 nicotinic acetylcholine receptor subunit is required
for normal synaptic function and integrity of the olivocochlear system},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {20594--20599},
number = {51},
month = dec,
abstract = {Although homomeric channels assembled from the {alpha}9 nicotinic
acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological,
anatomical, and molecular data suggest that native cholinergic olivocochlear
function is mediated via heteromeric nAChRs composed of both {alpha}9
and {alpha}10 subunits. To gain insight into {alpha}10 subunit function
in vivo, we examined olivo cochlear innervation and function in {alpha}10
null-mutant mice. Electrophysiological recordings from postnatal
(P) days P8-9 inner hair cells revealed ACh-gated currents in {alpha}10+/+
and {alpha}10+/- mice, with no detectable responses to ACh in {alpha}10-/-
mice. In contrast, a proportion of {alpha}10-/- outer hair cells
showed small ACh-evoked currents. In {alpha}10-/- mutant mice, olivocochlear
fiber stimulation failed to suppress distortion products, suggesting
that the residual {alpha}9 homomeric nAChRs expressed by outer hair
cells are unable to transduce efferent signals in vivo. Finally,
{alpha}10-/- mice exhibit both an abnormal olivocochlear morphology
and innervation to outer hair cells and a highly disorganized efferent
innervation to the inner hair cell region. Our results demonstrate
that {alpha}9-/- and {alpha}10-/- mice have overlapping but nonidentical
phenotypes. Moreover, {alpha}10 nAChR subunits are required for normal
olivocochlear activity because {alpha}9 homomeric nAChRs do not support
maintenance of normal olivocochlear innervation or function in {alpha}10-/-
mutant mice.},
url = {http://www.pnas.org/cgi/content/abstract/104/51/20594}
}
@ARTICLE{Vetter2009,
author = {Vetter, G. and Le Béchec, A. and Muller, J. and Muller, A. and Moes,
M. and Yatskou, M. and Al Tanoury, Z. and Poch, O. and Vallar, L.
and Friederich, E.},
title = {Time-resolved analysis of transcriptional events during SNAI1-triggered
epithelial to mesenchymal transition},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {385},
pages = {485--491},
number = {4},
month = aug,
abstract = {The transcription regulator SNAI1 triggers a transcriptional program
leading to epithelial to mesenchymal transition (EMT), providing
epithelial cells with mesenchymal features and invasive properties
during embryonic development and tumor progression. To identify early
transcriptional changes occurring during SNAI1-induced EMT, we performed
a time-resolved genome-scale study using human breast carcinoma cells
conditionally expressing SNAI1. The approach we developed for microarray
data analysis, allowed identifying three distinct EMT stages and
the temporal classification of genes. Importantly, we identified
unexpected, biphasic expression profiles of EMT-associated genes,
supporting their pivotal role during this process. Finally, we established
early EMT gene networks by identifying transcription factors and
their potential targets which may orchestrate early events of EMT.
Collectively, our work provides a framework for the identification
and future systematic analysis of novel genes which contribute to
SNAI1-triggered EMT.},
issn = {0006-291X},
keywords = {Epithelium to mesenchyme transition, SNAI1, Microarray, Functional
genomics},
url = {http://www.sciencedirect.com/science/article/B6WBK-4W8VW03-1/2/ed7f89eef10f1c9828994b752d038da3}
}
@ARTICLE{Vi2009,
author = {Vi, Linda and Feng, Lucy and Zhu, Rebecca D. and Wu, Yan and Satish,
Latha and Gan, Bing Siang and O'Gorman, David B.},
title = {Periostin differentially induces proliferation, contraction and apoptosis
of primary Dupuytren's disease and adjacent palmar fascia cells},
journal = {Experimental Cell Research},
year = {2009},
volume = {315},
pages = {3574--3586},
number = {20},
month = dec,
abstract = {Dupuytren's disease, (DD), is a fibroproliferative condition of the
palmar fascia in the hand, typically resulting in permanent contracture
of one or more fingers. This fibromatosis is similar to scarring
and other fibroses in displaying excess collagen secretion and contractile
myofibroblast differentiation. In this report we expand on previous
data demonstrating that POSTN mRNA, which encodes the extra-cellular
matrix protein periostin, is up-regulated in Dupuytren's disease
cord tissue relative to phenotypically normal palmar fascia. We demonstrate
that the protein product of POSTN, periostin, is abundant in Dupuytren's
disease cord tissue while little or no periostin immunoreactivity
is evident in patient-matched control tissues. The relevance of periostin
up-regulation in DD was assessed in primary cultures of cells derived
from diseased and phenotypically unaffected palmar fascia from the
same patients. These cells were grown in type-1 collagen-enriched
culture conditions with or without periostin addition to more closely
replicate the in vivo environment. Periostin was found to differentially
regulate the apoptosis, proliferation, [alpha] smooth muscle actin
expression and stressed Fibroblast Populated Collagen Lattice contraction
of these cell types. We hypothesize that periostin, secreted by disease
cord myofibroblasts into the extra-cellular matrix, promotes the
transition of resident fibroblasts in the palmar fascia toward a
myofibroblast phenotype, thereby promoting disease progression.},
issn = {0014-4827},
keywords = {Dupuytren's disease, Palmar fascia, Periostin, Myofibroblast, Cell
proliferation, Apoptosis, Contraction},
url = {http://www.sciencedirect.com/science/article/B6WFC-4WSY4GC-1/2/e4e39d0eec850c26ca9c622558b7fe75}
}
@ARTICLE{Vi2011,
author = {Vi, Linda and de Lasa, Cristina and DiGuglielmo, Gianni M and Dagnino,
Lina},
title = {Integrin-Linked Kinase Is Required for TGF-[beta]1 Induction of Dermal
Myofibroblast Differentiation},
journal = {J Invest Dermatol},
year = {2011},
volume = {131},
pages = {586--593},
number = {3},
month = mar,
issn = {0022-202X},
publisher = {The Society for Investigative Dermatology, Inc},
url = {http://dx.doi.org/10.1038/jid.2010.362}
}
@ARTICLE{Viatour2004,
author = {Viatour, Patrick and Dejardin, Emmanuel and Warnier, Michael and
Lair, Florence and Claudio, Estefania and Bureau, Fabrice and Marine,
Jean-Christophe and Merville, Marie-Paule and Maurer, Ulrich and
Green, Douglas and Piette, Jacques and Siebenlist, Ulrich and Bours,
Vincent and Chariot, Alain},
title = {GSK3-Mediated BCL-3 Phosphorylation Modulates Its Degradation and
Its Oncogenicity},
journal = {Molecular Cell},
year = {2004},
volume = {16},
pages = {35--45},
number = {1},
month = oct,
abstract = {The oncoprotein BCL-3 is a nuclear transcription factor that activates
NF-[kappa]B target genes through formation of heterocomplexes with
p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 kinases
have not been identified so far. In this report, we show that BCL-3
is a substrate for the protein kinase GSK3 and that GSK3-mediated
BCL-3 phosphorylation, which is inhibited by Akt activation, targets
its degradation through the proteasome pathway. This phosphorylation
modulates its association with HDAC1, -3, and -6 and attenuates its
oncogenicity by selectively controlling the expression of a subset
of newly identified target genes such as SLPI and Cxcl1. Our results
therefore suggest that constitutive BCL-3 phosphorylation by GSK3
regulates BCL-3 turnover and transcriptional activity.},
issn = {1097-2765},
url = {http://www.sciencedirect.com/science/article/B6WSR-4DGT7P2-4/2/80adc4ab495d6c8b2ccbddcef87d680d}
}
@ARTICLE{Vibhakar2007,
author = {Vibhakar, Rajeev and Foltz, Greg and Yoon, Jae-geun and Field, Lorie
and Lee, Hwahyung and Ryu, Gi-yung and Pierson, Jessica and Davidson,
Beverly and Madan, Anup},
title = {Dickkopf-1 is an epigenetically silenced candidate tumor suppressor
gene in medulloblastoma},
journal = {Neuro Oncology},
year = {2007},
volume = {9},
pages = {135--144},
number = {2},
month = apr,
abstract = {Medulloblastoma is a heterogeneous pediatric brain tumor with significant
therapy-related morbidity, its five-year survival rates ranging from
30% to 70%. Improvement in diagnosis and therapy requires better
understanding of medulloblastoma pathology. We used whole-genome
microarray analysis to identify putative tumor suppressor genes silenced
by epigenetic mechanisms in medulloblastoma. This analysis yielded
714 up-regulated genes in immortalized medulloblastoma cell line
D283 on treatment with histone deacetylase (HDAC) inhibitor trichostatin
A (TSA). Dickkopf-1 (DKK1), a Wnt antagonist, was found to be up-regulated
on HDAC inhibition. We examined DKK1 expression in primary medulloblastoma
cells and patient samples by reverse transcriptase PCR and found
it to be significantly down-regulated relative to normal cerebellum.
Transfection of a DKK1 gene construct into D283 cell lines suppressed
medulloblastoma tumor growth in colony focus assays by 60% (P < 0.001).
In addition, adenoviral vector-mediated expression of DKK1 in medulloblastoma
cells increased apoptosis fourfold (P < 0.001). These data reveal
that inappropriate histone modifications might deregulate DKK1 expression
in medulloblastoma tumorigenesis and block its tumor-suppressive
activity.},
url = {http://neuro-oncology.oxfordjournals.org/cgi/content/abstract/9/2/135}
}
@ARTICLE{Vicente2011,
author = {Vicente, Jorge and Cascon, Tomas and Vicedo, Begonya and Garcia-Agustin,
Pilar and Hamberg, Mats and Castresana, Carmen},
title = {Role of 9-Lipoxygenase and {alpha}-Dioxygenase Oxylipin Pathways
as Modulators of Local and Systemic Defense},
journal = {Mol Plant},
year = {2011},
pages = {ssr105},
abstract = {Plant 9-lipoxygenases (9-LOX) and -dioxygenases (-DOX) initiate the
synthesis of oxylipins after bacterial infection. Here, the role
of these enzymes in plants' defense was investigated using individual
Arabidopsis thaliana lox1 and dox1 mutants and a double lox1 dox1
mutant. Studies with Pseudomonas syringae pv. tomato (Pst) revealed
the enhanced susceptibility of lox1 to the virulent strain Pst DC3000
and the partial impairment of lox1 and dox1 mutants to activate systemic
acquired resistance. Notably, both defects were enhanced in the lox1
dox1 plants as compared with individual mutants. We found that pre-treatment
with 9-LOX- and -DOX-generated oxylipins protected plant tissues
against bacterial infection. The strongest effect in this respect
was exerted by 9-ketooctadecatrienoic acid (9-KOT), which is produced
from linolenic acid by 9-LOX. Quantification of 9-KOT revealed its
accumulation after bacterial infection. The levels were reduced in
lox1 and lox1 dox1 plants but strongly increased in the dox1 mutant
due to metabolic interaction of the two pathways. Transcriptional
analyses indicated that 9-KOT pre-treatment modifies hormone homeostasis
during bacterial infection. The nature of the changes detected suggested
that 9-KOT interferes with the hormonal changes caused by bacterial
effectors. This notion was substantiated by the finding that 9-KOT
failed to reduce the growth of PstDC3000hrpA, a mutant compromised
in effector secretion, and of the avirulent strain Pst DC3000 avrRpm1.
Further support for the action of the 9-LOX- and -DOX-oxylipin pathways
as modulators of hormone homeostasis was the observation that lox1
dox1 seedlings are hypersensitive to the growth-inhibitory effect
of ABA and showed enhanced activation of ABA-inducible marker genes
as compared with wild-type plants.},
doi = {10.1093/mp/ssr105},
eprint = {http://mplant.oxfordjournals.org/cgi/reprint/ssr105v1.pdf},
url = {http://mplant.oxfordjournals.org/cgi/content/abstract/ssr105v1}
}
@ARTICLE{Vickerman2011,
author = {Vickerman, Lori and Neufeld, Stanley and Cobb, John},
title = {Shox2 function couples neural, muscular and skeletal development
in the proximal forelimb},
journal = {Developmental Biology},
year = {2011},
volume = {350},
pages = {323--336},
number = {2},
month = feb,
abstract = {The mouse Shox2 gene codes for a homeodomain transcription factor
that is required to form the proximal bones of the limbs, the humerus
and femur. Shox2 is the only gene known to be essential for the specific
development of these skeletal elements. Shox2 is also of special
interest because it is closely related to the human SHOX gene, deficiencies
of which cause the short stature in Turner, Langer and Léri-Weill
syndromes. In order to understand in more detail the development
of the proximal limb, we searched for Shox2-dependent gene expression
patterns using Affymetrix microarrays. We compared the mRNA of Shox2-mutant
and wild-type forelimb buds at 10.5 and 11.5 days of embryonic development
(E10.5 and E11.5) and successfully identified a set of genes whose
wild-type expression pattern requires Shox2 function, as confirmed
by in situ hybridization for eleven of the candidates. Strikingly,
several of the identified genes were predicted to have functions
in tissues other than the skeleton, including nerves and muscle precursors,
prompting us to analyze neural and muscular patterning in Shox2 mutants.
We report here an axonal migration defect in Shox2 mutants resulting
in a profound innervation deficiency of the dorsal forelimb, including
the complete absence of the radial and axillary nerves. Muscular
development was also altered as early as E11.5. Specifically, the
triceps muscles that develop along the posterior face of the humerus
had severe abnormalities. These data demonstrate that Shox2 is required
for normal skeletal, neural and muscular development in the forelimb
at a similar early developmental stage in each tissue.},
issn = {0012-1606},
keywords = {Limb development, Axonal pathfinding, Muscle patterning, Shox2, Mup1,
Epha7},
url = {http://www.sciencedirect.com/science/article/pii/S0012160610012364}
}
@ARTICLE{Vickers2011,
author = {Alison E.M. Vickers and Robyn Fisher and Peter Olinga and Sharon
Dial},
title = {Repair pathways evident in human liver organ slices},
journal = {Toxicology in Vitro},
year = {2011},
volume = {25},
pages = {1485 - 1492},
number = {7},
abstract = {The extension of human liver slice culture viability for several days
broadens the potential of this ex vivo model for characterizing pathways
of organ injury and repair, and allows for the multiple dosing of
compounds. Extended viability is demonstrated by continued synthesis
of GSH and ATP, and maintenance of intracellular K+ levels. Gene
expression profiling revealed the activation of regeneration pathways
via increased expression of collagens (I, IV, and V), laminins, ninjurin,
growth factors (EGF, epiregulin, and TGF-β1), matrix metalloproteinase-7,
and insulin like growth factor 5. Collagen IV protein levels began
to increase by day 4 of culture. Some markers of hepatic stellate
cells, detected by RT-PCR, were up-regulated (HSP47, αSMA, pro-collagen
1a1, PDGF receptor, thrombospondin-2) with time in culture, while
other markers exhibited no change or were down-regulated (αB-crystallin,
synaptophysin), suggesting that the induction of regenerative pathways
may in part be the role of the stellate cells as well as resident
fibroblasts. Complimentary to the gene expression was evidence of
regeneration in the human liver slices, as evaluated by histopathology.
Improvements in organ acquisition, organ slice preparation and culture
methods demonstrates that organ slice viability, integrity and morphology
can be extended reproducibly for several days in culture which allows
for the investigation of injury and repair processes.},
doi = {10.1016/j.tiv.2011.04.029},
issn = {0887-2333},
keywords = {Human liver slices},
url = {http://www.sciencedirect.com/science/article/pii/S0887233311001287}
}
@ARTICLE{Vickers2010,
author = {Vickers, Alison E.M. and Sinclair, John R. and Fisher, Robyn L. and
Morris, Stephen R. and Way, William},
title = {Blood cell oxidative stress precedes hemolysis in whole blood-liver
slice co-cultures of rat, dog, and human tissues},
journal = {Toxicology and Applied Pharmacology},
year = {2010},
volume = {244},
pages = {354--365},
number = {3},
month = may,
abstract = {A novel in vitro model to investigate time-dependent and concentration-dependent
responses in blood cells and hemolytic events is studied for rat,
dog, and human tissues. Whole blood is co-cultured with a precision-cut
liver slice. Methimazole (MMI) was selected as a reference compound,
since metabolism of its imidazole thione moiety is linked with hematologic
disorders and hepatotoxicity. An oxidative stress response occurred
in all three species, marked by a decline in blood GSH levels by
24 h that progressed, and preceded hemolysis, which occurred at high
MMI concentrations in the presence of a liver slice with rat (>= 1000
[mu]M at 48 h) and human tissues (>= 1000 [mu]M at 48 h, >= 750 [mu]M
at 72 h) but not dog. Human blood-only cultures exhibited a decline
of GSH levels but minimal to no hemolysis. The up-regulation of liver
genes for heme degradation (Hmox1 and Prdx1), iron cellular transport
(Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were
early markers of the oxidative stress response. The up-regulation
of the Kupffer cell lectin Lgals3 gene expression indicated a response
to damaged red blood cells, and Hp (haptoglobin) up-regulation is
indicative of increased hemoglobin uptake. Up-regulation of liver
IL-6 and IL-8 gene expression suggested an activation of an inflammatory
response by liver endothelial cells. In summary, MMI exposure led
to an oxidative stress response in blood cells, and an up-regulation
of liver genes involved with oxidative stress and heme homeostasis,
which was clearly separate and preceded frank hemolysis.},
issn = {0041-008X},
keywords = {Oxidative stress and in vitro hemolysis model with rat, Dog and human
tissue},
url = {http://www.sciencedirect.com/science/article/B6WXH-4YB78T6-2/2/ccd2d1fd8efadafa48e815bdd2783148}
}
@ARTICLE{Vickers2011a,
author = {Vickers, Kasey C. and Palmisano, Brian T. and Shoucri, Bassem M.
and Shamburek, Robert D. and Remaley, Alan T.},
title = {MicroRNAs are transported in plasma and delivered to recipient cells
by high-density lipoproteins},
journal = {Nat Cell Biol},
year = {2011},
volume = {13},
pages = {423--433},
number = {4},
month = apr,
comment = {10.1038/ncb2210},
issn = {1465-7392},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/ncb2210}
}
@ARTICLE{Vidal2005,
author = {Vidal, J.D. and VandeVoort, C.A. and Marcus, C.B. and Lazarewicz,
N.R. and Conley, A.J.},
title = {2,3,7,8-Tetrachlorodibenzo-p-dioxin induces CYP1B1 expression in
human luteinized granulosa cells},
journal = {Archives of Biochemistry and Biophysics},
year = {2005},
volume = {439},
pages = {53--60},
number = {1},
month = jul,
abstract = {The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) is a reproductive toxicant in multiple species; however, mechanisms
and direct ovarian effects are poorly understood. DNA microarrays
were used to characterize gene expression profiles of human luteinized
granulosa cells (HLGCs) exposed to TCDD in primary cultures. Exposure
to 10 nM TCDD for 24 h induced a significant increase in CYP1B1,
while few other genes responded. TaqMan PCR and Western immunoblotting
demonstrated that induction was dose-dependent. Additionally, the
microsomal form of catechol-O-methyltransferase (COMT) was highly
expressed in HLGCs, along with only fractional amounts of the soluble
form. This is the first report of CYP1B1 and COMT expression, and
CYP1B1 induction, in cells from the human ovary. The role of CYP1B1
in the oxidative metabolism of estrogens and potential generation
of DNA adducts in the ovary may have significant consequences for
oocyte quality, corpus luteum function, and ovarian carcinogenesis.},
issn = {0003-9861},
keywords = {2,3,7,8-Tetrachlorodibenzo-p-dioxin, CYP1B1, Catechol-O-methyltransferase,
Ovary, Corpus luteum, Microarrays},
url = {http://www.sciencedirect.com/science/article/B6WB5-4G7NM0D-2/2/f00473300c1f13b932dbd0b124a50791}
}
@ARTICLE{Viegas2007,
author = {Viegas, Marcelo H. and Gehring, Niels H. and Breit, Stephen and Hentze,
Matthias W. and Kulozik, Andreas E.},
title = {The abundance of RNPS1, a protein component of the exon junction
complex, can determine the variability in efficiency of the Nonsense
Mediated Decay pathway},
journal = {Nucleic Acids Res.},
year = {2007},
volume = {35},
pages = {4542--4551},
number = {13},
month = jul,
abstract = {Nonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA
surveillance that ensures rapid degradation of mRNAs containing premature
translation termination codons (PTCs) in eukaryotes. NMD has been
shown to also regulate normal gene expression and thus emerged as
one of the key post-transcriptional mechanisms of gene regulation.
Recently, NMD efficiency has been shown to vary between cell types
and individuals thus implicating NMD as a modulator of genetic disease
severity. We have now specifically analysed the molecular mechanism
of variable NMD efficiency and first established an assay system
for the quantification of NMD efficiency, which is based on carefully
validated cellular NMD target transcripts. In a HeLa cell model system,
NMD efficiency is shown to be remarkably variable and to represent
a stable characteristic of different strains. In one of these strains,
low NMD efficiency is shown to be functionally related to the reduced
abundance of the exon junction component RNPS1. Furthermore, restoration
of functional RNPS1 expression, but not of NMD-inactive mutant proteins,
also restores efficient NMD in this model. We conclude that cellular
concentrations of RNPS1 can modify NMD efficiency and propose that
cell type specific co-factor availability represents a novel principle
that controls NMD.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/35/13/4542}
}
@ARTICLE{Vieira2011,
author = {Vieira, Florbela and Gregorio, Silvia and Ferraresso, Serena and
Thorne, Michael and Costa, Rita and Milan, Massimo and Bargelloni,
Luca and Clark, Melody and Canario, Adelino and Power, Deborah},
title = {Skin healing and scale regeneration in fed and unfed sea bream, Sparus
auratus},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {490},
number = {1},
abstract = {BACKGROUND:Fish scales are an important reservoir of calcium and phosphorus
and together with the skin function as an integrated barrier against
environmental changes and external aggressors. Histological studies
have revealed that the skin and scales regenerate rapidly in fish
when they are lost or damaged. In the present manuscript the histological
and molecular changes underlying skin and scale regeneration in fed
and fasted sea bream (Sparus auratus) were studied using a microarray
3 and 7 days after scale removal to provide a comprehensive molecular
understanding of the early stages of these processes.RESULTS:Histological
analysis of skin/scales revealed 3 days after scale removal re-epithelisation
and formation of the scale pocket had occurred and 53 and 109 genes
showed significant up or down-regulation, respectively. Genes significantly
up-regulated were involved in cell cycle regulation, cell proliferation
and adhesion, immune response and antioxidant activities. 7 days
after scale removal a thin regenerated scale was visible and only
minor changes in gene expression occurred. In animals that were fasted
to deplete mineral availability the expression profiles centred on
maintaining energy homeostasis. The utilisation of fasting as a treatment
emphasised the competing whole animal physiological requirements
with regard to barrier repair, infection control and energy homeostasis.CONCLUSIONS:The
identification of numerous genes involved in the mitotic checkpoint
and cell proliferation indicate that the experimental procedure may
be useful for understanding cell proliferation and control in vertebrates
within the context of the whole animal physiology. In response to
skin damage genes of immune surveillance were up-regulated along
with others involved in tissue regeneration required to rapidly re-establish
barrier function. Additionally, candidate fish genes were identified
that may be involved in cytoskeletal re-modelling, mineralization
and stem cells, which are of potential use in aquaculture and fish
husbandry, as they may impact on the ability of the fish to produce
structural proteins, such as muscle, efficiently.},
doi = {10.1186/1471-2164-12-490},
issn = {1471-2164},
pubmedid = {21981800},
url = {http://www.biomedcentral.com/1471-2164/12/490}
}
@ARTICLE{Vierlinger2011,
author = {Vierlinger, Klemens and Mansfeld, Markus and Koperek, Oskar and Nöhammer,
Christa and Kaserer, Klaus and Leisch, Friedrich},
title = {Identification of SERPINA1 as single marker for papillary thyroid
carcinoma through microarray meta analysis and quantification of
its discriminatory power in independent validation},
journal = {BMC Medical Genomics},
year = {2011},
volume = {4},
pages = {30},
number = {1},
abstract = {BACKGROUND:Several DNA microarray based expression signatures for
the different clinically relevant thyroid tumor entities have been
described over the past few years. However, reproducibility of these
signatures is generally low, mainly due to study biases, small sample
sizes and the highly multivariate nature of microarrays. While there
are new technologies available for a more accurate high throughput
expression analysis, we show that there is still a lot of information
to be gained from data deposited in public microarray databases.
In this study we were aiming (1) to identify potential markers for
papillary thyroid carcinomas through meta analysis of public microarray
data and (2) to confirm these markers in an independent dataset using
an independent technology.METHODS:We adopted a meta analysis approach
for four publicly available microarray datasets on papillary thyroid
carcinoma (PTC) nodules versus nodular goitre (NG) from N2-frozen
tissue. The methodology included merging of datasets, bias removal
using distance weighted discrimination (DWD), feature selection/inference
statistics, classification/crossvalidation and gene set enrichment
analysis (GSEA). External Validation was performed on an independent
dataset using an independent technology, quantitative RT-PCR (RT-qPCR)
in our laboratory.RESULTS:From meta analysis we identified one gene
(SERPINA1) which identifies papillary thyroid carcinoma against benign
nodules with 99% accuracy (n = 99, sensitivity = 0.98, specificity
= 1, PPV = 1, NPV = 0.98). In the independent validation data, which
included not only PTC and NG, but all major histological thyroid
entities plus a few variants, SERPINA1 was again markedly up regulated
(36-fold, p = 1:3*10-10) in PTC and identification of papillary carcinoma
was possible with 93% accuracy (n = 82, sensitivity = 1, specificity
= 0.90, PPV = 0.76, NPV = 1). We also show that the extracellular
matrix pathway is strongly activated in the meta analysis data, suggesting
an important role of tumor-stroma interaction in the carcinogenesis
of papillary thyroid carcinoma.CONCLUSIONS:We show that valuable
new information can be gained from meta analysis of existing microarray
data deposited in public repositories. While single microarray studies
rarely exhibit a sample number which allows robust feature selection,
this can be achieved by combining published data using DWD. This
approach is not only efficient, but also very cost-effective. Independent
validation shows the validity of the results from this meta analysis
and confirms SERPINA1 as a potent mRNA marker for PTC in a total
(meta analysis plus validation) of 181 samples.},
doi = {10.1186/1755-8794-4-30},
issn = {1755-8794},
pubmedid = {21470421},
url = {http://www.biomedcentral.com/1755-8794/4/30}
}
@ARTICLE{Viertlboeck2008,
author = {Viertlboeck, Birgit C. and Hanczaruk, Matthias A. and Schmitt, Ferdinand
C.A. and Schmitt, Ramona and Göbel, Thomas W.},
title = {Characterization of the chicken CD200 receptor family},
journal = {Molecular Immunology},
year = {2008},
volume = {45},
pages = {2097--2105},
number = {7},
month = apr,
abstract = {The modulation of myeloid cells via inhibitory and activating immunoglobulin
superfamily members has been a subject of intense study in mammals.
One such example is the inhibitory receptor for CD200, which is shown
to regulate the activation threshold of myeloid cells by interaction
with the broadly distributed CD200 molecule. By looking at sequence
homology and synteny conservations in the chicken genome, we identified
two members of the CD200 receptor family in chicken on chromosome
one. Cloning and further characterization of the protein sequence
yielded a potentially inhibitory ggCD200R-B1 with a splice variant
lacking a transmembrane region and a potentially soluble ggCD200R-S1.
Both showed a typical V/C2-set Ig domain arrangement and we present
evidence that these two genes have evolved by gene duplication. The
inhibitory receptor displayed an uncharged transmembrane region and
a long cytoplasmic tail encoding four tyrosine residues, one of them
embedded in a motif similar to the mammalian NPxY motif. Further
characterization of ggCD200R-B1 showed that it is expressed as a
highly glycosylated protein and that its cytoplasmic tyrosine residues
can be phosphorylated. Real-time RT-PCR analysis of various tissues
and primary cells showed that ggCD200R-B1 is predominantly expressed
in macrophages, whereas ggCD200R-S1 is highly expressed in peripheral
blood mononuclear cells, but not macrophages. In summary, we showed
that there is a homologue of mammalian CD200R conserved in chicken
suggesting a similar function in avian species. Furthermore, the
presence of potentially soluble CD200R molecules implies an important
role for these in the regulation of myeloid cells in chicken.},
issn = {0161-5890},
keywords = {CD200 receptor, Ig-like receptor, Chicken, Phylogeny, Macrophages},
url = {http://www.sciencedirect.com/science/article/B6T9R-4R5G7YP-4/2/f80b055909027362a057e0b81e98f565}
}
@ARTICLE{Viertlboeck2009,
author = {Viertlboeck, Birgit C. and Schmitt, Ramona and Hanczaruk, Matthias
A. and Crooijmans, Richard P. M. A. and Groenen, Martien A. M. and
Gobel, Thomas W.},
title = {A Novel Activating Chicken IgY FcR Is Related to Leukocyte Receptor
Complex (LRC) Genes but Is Located on a Chromosomal Region Distinct
from the LRC and FcR Gene Clusters},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {1533--1540},
number = {3},
month = feb,
abstract = {FcRs have multifaceted roles in the immune system. Chicken FcRs were
demonstrated on macrophages decades ago; however, only recently the
chicken Ig-like receptor AB1, encoded in the leukocyte receptor complex,
was molecularly identified as a high-affinity FcR. The present study
was initiated to identify additional receptors with the capability
to bind chicken immunoglobulins. Based on database searches, we cloned
a novel chicken FcR, designated gallus gallus FcR (ggFcR), which
was shown to bind selectively chicken IgY. The receptor consists
of four extracellular C2-set Ig domains, followed by a transmembrane
region containing arginine as a positively charged amino acid and
a short cytoplasmic tail. ggFcR associates with the common {gamma}-chain,
indicative for an activating receptor, and real-time RT-PCR revealed
high expression on PBMC, thrombocytes, and macrophages. The genomic
organization is similar to most Ig-like receptor genes, where each
Ig domain is encoded by a separate exon. Additionally, the ggFcR
signal peptide is encoded by two exons, the second of which is 36
bp, a hallmark for genes encoded in the leukocyte receptor complex.
Phylogenetic analysis also showed a relationship to genes encoded
in the leukocyte receptor complex. Surprisingly, ggFcR is not encoded
in the leukocyte receptor complex, but it is located as a single
isolated gene at the extremity of chicken chromosome 20.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/3/1533}
}
@ARTICLE{Viertlboeck2007,
author = {Viertlboeck, Birgit C. and Schweinsberg, Sonja and Hanczaruk, Matthias
A. and Schmitt, Ramona and Du Pasquier, Louis and Herberg, Friedrich
W. and Gobel, Thomas W.},
title = {The chicken leukocyte receptor complex encodes a primordial, activating,
high-affinity IgY Fc receptor},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {11718--11723},
number = {28},
month = jul,
abstract = {Fc receptors are key players of the immune system that link the fine
specificity of immunoglobulins and innate effector responses. Here,
we describe a nonmammalian Fc{gamma} receptor, CHIR-AB1, a member
of the leukocyte receptor complex, that binds IgY with high affinity
with its single Ig domain. It is expressed on immature and mature
B lymphocytes, monocytes, macrophages, and natural killer cells and
harbors motifs of activating and inhibitory Fc receptors. In the
absence of Fc{varepsilon}RI{gamma}, CHIR-AB1 can be expressed on
B cells but cross-linking does not induce intracellular calcium release.
In contrast, cells expressing CHIR-AB1 and Fc{varepsilon}RI{gamma}
are triggered to release intracellular calcium upon stimulation with
heat-aggregated IgY. CHIR-AB1 thus represents a primordial Fc receptor
that combines features of different mammalian counterparts.},
url = {http://www.pnas.org/cgi/content/abstract/104/28/11718}
}
@ARTICLE{Vietina2011,
author = {Vietina, Michelangelo and Agrimonti, Caterina and Marmiroli, Marta
and Bonas, Urbana and Marmiroli, Nelson},
title = {Applicability of SSR markers to the traceability of monovarietal
olive oils},
journal = {Journal of the Science of Food and Agriculture},
year = {2011},
volume = {91},
pages = {1381--1391},
number = {8},
abstract = {Abstract BACKGROUND: To protect the features and authenticity of food
products, the European Commission enforces two certification labels:
Protected Designation of Origin (PDO) and Protected Geographical
Indication (PGI). EEC Regulation No. 510/2006 imposes criteria for
labelling, production and commercialisation of olive oil. Since plant
genotype is a major determinant in establishing the PDO and PGI labels,
methods to ascertain the varieties present in a batch of olive oil
are essential in validating product conformity. The traceability
of olive oil can be assessed through simple sequence repeat (SSR)
co-dominant markers targeted to specific regions of DNA from olive
cultivars.RESULTS: Twenty-one monovarietal olive oils were analysed
with nine nuclear and two shortened SSRs. For each marker the correspondence
of allelic profile with the reference cultivar, the reproducibility
of profiles in different DNA extractions and the polymorphism information
content were determined.CONCLUSION: The results showed that using
a panel of SSR markers such as those described in this paper allows
one to make a reliable attribution of an olive oil to a specific
cultivar. Copyright © 2011 Society of Chemical Industry},
doi = {10.1002/jsfa.4317},
issn = {1097-0010},
keywords = {olive oil, food genomics, SSR markers, shortened SSR, DNA extraction},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jsfa.4317}
}
@ARTICLE{ViganA²2011,
author = {Viganò, Agnese and Vasso, Michele and Caretti, Anna and Bravatà ,
Valentina and Terraneo, Laura and Fania, Chiara and Capitanio, Daniele
and Samaja, Michele and Gelfi, Cecilia},
title = {Protein modulation in mouse heart under acute and chronic hypoxia},
journal = {PROTEOMICS},
year = {2011},
volume = {11},
pages = {4202--4217},
number = {21},
abstract = {Exploring cellular mechanisms underlying beneficial and detrimental
responses to hypoxia represents the object of the present study.
Signaling molecules controlling adaptation to hypoxia (HIF-1α),
energy balance (AMPK), mitochondrial biogenesis (PGC-1α), autophagic/apoptotic
processes regulation and proteomic dysregulation were assessed. Responses
to acute hypoxia (AH) and chronic hypoxia (CH) in mouse heart proteome
were detected by 2-D DIGE, mass spectrometry and antigen–antibody
reactions. Both in AH and CH, the results indicated a deregulation
of proteins related to sarcomere stabilization and muscle contraction.
Neither in AH nor in CH the HIF-1α stabilization was observed. In
AH, the metabolic adaptation to lack of oxygen was controlled by
AMPK activation and sustained by an up-regulation of adenosylhomocysteinase
and acetyl-CoA synthetase. AH was characterized by the mitophagic
protein Bnip 3 increment. PGC-1α, a master regulator of mitochondrial
biogenesis, was down-regulated. CH was characterized by the up-regulation
of enzymes involved in antioxidant defense, in aldehyde bio-product
detoxification and in misfolded protein degradation. In addition,
a general down-regulation of enzymes controlling anaerobic metabolism
was observed. After 10 days of hypoxia, cardioprotective molecules
were substantially decreased whereas pro-apoptotic molecules increased
accompained by down-regulation of specific target proteins.},
doi = {10.1002/pmic.201000804},
issn = {1615-9861},
keywords = {AMPK, Animal proteomics, Apoptosis, Autophagy, Heart, Hypoxia},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.201000804}
}
@ARTICLE{Vigerust2012,
author = {Natalya Filipchuk Vigerust and Daniel Cacabelos and Lena Burri and
Kjetil Berge and Hege Wergedahl and Bjørn Christensen and Manuel
Portero-Otin and Asgaut Viste and Reinald Pamplona and Rolf Kristian
Berge and Bodil Bjørndal},
title = {Fish oil and 3-thia fatty acid have additive effects on lipid metabolism
but antagonistic effects on oxidative damage when fed to rats for
50 weeks},
journal = {The Journal of Nutritional Biochemistry},
year = {2012},
pages = { - },
number = {0},
abstract = {The 3-thia fatty acid tetradecylthioacetic acid (TTA) is a synthetic
modified fatty acid, which, similar with dietary fish oil (FO), influences
the regulation of lipid metabolism, the inflammatory response and
redox status. This study was aimed to penetrate the difference in
TTA's mode of action compared to FO in a long-term experiment (50
weeks of feeding). Male Wistar rats were fed a control, high-fat
(25% w/v) diet or a high-fat diet supplemented with either TTA (0.375%
w/v) or FO (10% w/v) or their combination. Plasma fatty acid composition,
hepatic lipids and expression of relevant genes in the liver and
biomarkers of oxidative damage to protein were assessed at the end
point of the experiment. Both supplements given in combination demonstrated
an additive effect on the decrease in plasma cholesterol levels.
The FO diet alone led to removal of plasma cholesterol and a concurrent
cholesterol accumulation in liver; however, with TTA cotreatment,
the hepatic cholesterol level was significantly reduced. Dietary
FO supplementation led to an increased oxidative damage, as seen
by biomarkers of protein oxidation and lipoxidation. Tetradecylthioacetic
acid administration reduced the levels of these biomarkers confirming
its protective role against lipoxidation and protein oxidative damage.
Our findings explore the lipid reducing effects of TTA and FO and
demonstrate that these bioactive dietary compounds might act in a
different manner. The experiment confirms the antioxidant capacity
of TTA, showing an improvement in FO-induced oxidative stress.},
doi = {10.1016/j.jnutbio.2011.08.006},
issn = {0955-2863},
keywords = {Reactive oxygen species},
url = {http://www.sciencedirect.com/science/article/pii/S0955286311002439}
}
@ARTICLE{Vigetti2011,
author = {Vigetti, Davide and Rizzi, Manuela and Moretto, Paola and Deleonibus,
Sara and Dreyfuss, Jonathan M. and Karousou, Evgenia and Viola, Manuela
and Clerici, Moira and Hascall, Vincent C. and Ramoni, Marco F. and
De Luca, Giancarlo and Passi, Alberto},
title = {Glycosaminoglycans and Glucose Prevent Apoptosis in 4-Methylumbelliferone-treated
Human Aortic Smooth Muscle Cells},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {34497-34503},
number = {40},
abstract = {Smooth muscle cells (SMCs) have a pivotal role in cardiovascular diseases
and are responsible for hyaluronan (HA) deposition in thickening
vessel walls. HA regulates SMC proliferation, migration, and inflammation,
which accelerates neointima formation. We used the HA synthesis inhibitor
4-methylumbelliferone (4-MU) to reduce HA production in human aortic
SMCs and found a significant increase of apoptotic cells. Interestingly,
the exogenous addition of HA together with 4-MU reduced apoptosis.
A similar anti-apoptotic effect was observed also by adding other
glycosaminoglycans and glucose to 4-MU-treated cells. Furthermore,
the anti-apoptotic effect of HA was mediated by Toll-like receptor
4, CD44, and PI3K but not by ERK1/2.},
doi = {10.1074/jbc.M111.266312},
eprint = {http://www.jbc.org/cgi/reprint/286/40/34497.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/40/34497}
}
@ARTICLE{Vigl2011,
author = {Vigl, Benjamin and Aebischer, David and Nitschke, Maximilian and
Iolyeva, Maria and Rothlin, Tamara and Antsiferova, Olga and Halin,
Cornelia},
title = {Tissue inflammation modulates gene expression of lymphatic endothelial
cells and dendritic cell migration in a stimulus-dependent manner},
journal = {Blood},
year = {2011},
volume = {118},
pages = {205-215},
number = {1},
abstract = {Chemokines and adhesion molecules up-regulated in lymphatic endothelial
cells (LECs) during tissue inflammation are thought to enhance dendritic
cell (DC) migration to draining lymph nodes, but the in vivo control
of this process is not well understood. We performed a transcriptional
profiling analysis of LECs isolated from murine skin and found that
inflammation induced by a contact hypersensitivity (CHS) response
up-regulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory
chemokines. Importantly, the lymphatic markers Prox-1, VEGFR3, and
LYVE-1 were significantly down-regulated during CHS. By contrast,
skin inflammation induced by complete Freund adjuvant induced a different
pattern of chemokine and lymphatic marker gene expression and almost
no ICAM-1 up-regulation in LECs. Fluorescein isothiocyanate painting
experiments revealed that DC migration to draining lymph nodes was
more strongly increased in complete Freund adjuvant-induced than
in CHS-induced inflammation. Surprisingly, DC migration did not correlate
with the induction of CCL21 and ICAM-1 protein in LECs. Although
the requirement for CCR7 signaling became further pronounced during
inflammation, CCR7-independent signals had an additional, albeit
moderate, impact on enhancing DC migration. Collectively, these findings
indicate that DC migration in response to inflammation is stimulus-specific,
mainly CCR7-dependent, and overall only moderately enhanced by LEC-induced
genes other than CCL21.},
doi = {10.1182/blood-2010-12-326447},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/1/205.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/1/205}
}
@ARTICLE{Vigneault2009,
author = {Vigneault, Christian and Gravel, Catherine and Vallee, Maud and McGraw,
Serge and Sirard, Marc-Andre},
title = {Unveiling the bovine embryo transcriptome during the maternal-to-embryonic
transition},
journal = {Reproduction},
year = {2009},
volume = {137},
pages = {245--257},
number = {2},
month = feb,
abstract = {Bovine early embryos are transcriptionally inactive and subsist through
the initial developmental stages by the consumption of the maternal
supplies provided by the oocyte until its own genome activation.
In bovine, the activation of transcription occurs during the 8- to
16-cell stages and is associated with a phase called the maternal-to-embryonic
transition (MET) where maternal mRNA are replaced by embryonic ones.
Although the importance of the MET is well accepted, since its inhibition
blocks embryonic development, very little is known about the transcripts
expressed at this crucial step in embryogenesis. In this study, we
generated and characterized a cDNA library enriched in embryonic
transcripts expressed at the MET in bovine. Suppression subtractive
hybridization followed by microarray hybridization was used to isolate
more than 300 different transcripts overexpressed in untreated late
eight-cell embryos compared with those treated with the transcriptional
inhibitor, {alpha}-amanitin. Validation by quantitative RT-PCR of
15 genes from this library revealed that they had remarkable consistency
with the microarray data. The transcripts isolated in this cDNA library
have an interesting composition in terms of molecular functions;
the majority is involved in gene transcription, RNA processing, or
protein biosynthesis, and some are potentially involved in the maintenance
of pluripotency observed in embryos. This collection of genes associated
with the MET is a novel and potent tool that will be helpful in the
understanding of particular events such as the reprogramming of somatic
cells by nuclear transfer or for the improvement of embryonic culture
conditions.},
url = {http://www.reproduction-online.org/cgi/content/abstract/137/2/245}
}
@ARTICLE{Vigneswaran2006,
author = {Vigneswaran, Nadarajah and Beckers, Simone and Waigel, Sabine and
Mensah, John and Wu, Jean and Mo, Juan and Fleisher, Kenneth E. and
Bouquot, Jerry and Sacks, Peter G. and Zacharias, Wolfgang},
title = {Increased EMMPRIN (CD 147) expression during oral carcinogenesis},
journal = {Experimental and Molecular Pathology},
year = {2006},
volume = {80},
pages = {147--159},
number = {2},
month = apr,
abstract = {Gene expression profiling of oral premalignant (OPM) cells and normal
oral epithelial (NOR) cells showed that EMMPRIN expression was markedly
upregulated in OPM cells compared to NOR cells. We used an oral squamous
cell carcinoma (OSCC) progression model composed of cell lines, organotypic
cultures and tissue specimens to characterize EMMPRIN expression
patterns by microarray analysis, qRT-PCR, Western blotting and immunohistochemistry.
EMMPRIN levels are elevated in OPM and primary and metastatic OSCC
cells as compared to NOR. EMMPRIN was detected as high and low glycosylated
forms in the OPM and OSCC cellular extracts and was released in the
media by OSCC cells but not by OPM cells. EMMPRIN expression in an
organotypic culture model of normal and OPM mucosae mirrored the
expression patterns in the respective tissues in vivo. EMMPRIN expression
was limited to basal cells of normal, benign hyperkeratotic and inflammatory
(lichen planus) oral mucosa. EMMPRIN expression is increased in dysplastic
leukoplakias spreading to more superficial layers, and its expression
levels correlated significantly with the degree of dysplasia. Primary
and metastatic OSCC showed strong cell surface expression of EMMPRIN.
These results suggest that EMMPRIN overexpression occurs at a very
early stage of oral carcinogenesis and plays a contributing role
in OSCC tumorigenesis.},
issn = {0014-4800},
keywords = {Microarray analysis, EMMPRIN, Oral cancer, Organotypic culture, Leukoplakia},
url = {http://www.sciencedirect.com/science/article/B6WFB-4HNS6HK-1/2/cf4212924e1c28f37794ea3bcfda7bf2}
}
@ARTICLE{Viguerie2004,
author = {Viguerie, Nathalie and Clement, Karine and Barbe, Pierre and Courtine,
Melanie and Benis, Arriel and Larrouy, Dominique and Hanczar, Blaise
and Pelloux, Veronique and Poitou, Christine and Khalfallah, Yadh
and Barsh, Gregory S. and Thalamas, Claire and Zucker, Jean-Daniel
and Langin, Dominique},
title = {In Vivo Epinephrine-Mediated Regulation of Gene Expression in Human
Skeletal Muscle},
journal = {J. Clin. Endocrinol. Metab.},
year = {2004},
volume = {89},
pages = {2000--2014},
number = {5},
month = may,
abstract = {The stress hormone epinephrine produces major physiological effects
on skeletal muscle. Here we determined skeletal muscle mRNA expression
profiles before and during a 6-h epinephrine infusion performed in
nine young men. Stringent statistical analysis of data obtained using
43,000 cDNA element microarrays showed that 1206 and 474 genes were
up- and down-regulated, respectively. Microarray data were validated
using reverse transcription quantitative PCR. Gene classification
was performed through data mining of Gene Ontology annotations, cluster
analysis of regulated genes among 14 human tissues, and correlation
analysis of mRNA and clinical parameter variations. Evidence of an
autoregulatory control was provided by the regulation of key genes
of the cAMP-dependent transcription pathway. Genes with known functional
cAMP response elements were regulated by the hormone. The impact
on metabolism was illustrated by coordinated regulations of genes
involved in carbohydrate and protein metabolisms. Epinephrine had
a profound effect on genes involved in immunity and inflammatory
response, a previously unappreciated aspect of catecholamine action.
Information on 526 mRNAs corresponded to genes of unknown function.
These data define the molecular signatures of epinephrine action
in human skeletal muscle. They may contribute to the understanding
of skeletal muscle alterations observed in pathological conditions
characterized by sympathetic nervous system overdrive.},
url = {http://jcem.endojournals.org/cgi/content/abstract/89/5/2000}
}
@ARTICLE{VijayKumar2011,
author = {Vijay Kumar, Nallani and Rangarajan, Pundi N.},
title = {Catabolite repression of phosphoenolpyruvate carboxykinase by a zinc
finger protein under biotin- and pyruvate carboxylase-deficient conditions
in Pichia pastoris},
journal = {Microbiology},
year = {2011},
volume = {157},
pages = {3361-3369},
number = {12},
abstract = {We have identified a methanol- and biotin-starvation-inducible zinc
finger protein named ROP [repressor of phosphoenolpyruvate carboxykinase
(PEPCK)] in the methylotrophic yeast Pichia pastoris. When P. pastoris
strain GS115 (wild-type, WT) is cultured in biotin-deficient, glucose-ammonium
(Bio-) medium, growth is suppressed due to the inhibition of anaplerotic
synthesis of oxaloacetate, catalysed by the biotin-dependent enzyme
pyruvate carboxylase (PC). Deletion of ROP results in a strain ({Delta}ROP)
that can grow under biotin-deficient conditions due to derepression
of a biotin- and PC-independent pathway of anaplerotic synthesis
of oxaloacetate. Northern analysis as well as microarray expression
profiling of RNA isolated from WT and {Delta}ROP strains cultured
in Bio- medium indicate that expression of the phosphoenolpyruvate
carboxykinase gene (PEPCK) is induced in {Delta}ROP during biotin-
or PC-deficiency even under glucose-abundant conditions. There is
an excellent correlation between PEPCK expression and growth of {Delta}ROP
in Bio- medium, suggesting that ROP-mediated regulation of PEPCK
may have a crucial role in the biotin- and PC-independent growth
of the {Delta}ROP strain. To our knowledge, ROP is the first example
of a zinc finger transcription factor involved in the catabolite
repression of PEPCK in yeast cells cultured under biotin- or PC-deficient
and glucose-abundant conditions.},
doi = {10.1099/mic.0.053488-0},
eprint = {http://mic.sgmjournals.org/cgi/reprint/157/12/3361.pdf},
url = {http://mic.sgmjournals.org/cgi/content/abstract/157/12/3361}
}
@ARTICLE{Vijayan2011,
author = {Vijayan, Vikram and Jain, Isha and O'Shea, Erin},
title = {A high resolution map of a cyanobacterial transcriptome},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R47},
number = {5},
abstract = {BACKGROUND:Previous molecular and mechanistic studies have identified
several principles of prokaryotic transcription, but less is known
about the global transcriptional architecture of bacterial genomes.
Here we perform a comprehensive study of a cyanobacterial transcriptome,
that of Synechococcus elongatus PCC 7942, generated by combining
three high-resolution data sets: RNA sequencing, tiling expression
microarrays, and RNA polymerase chromatin immunoprecipitation sequencing.RESULTS:We
report absolute transcript levels, operon identification, and high-resolution
mapping of 5' and 3' ends of transcripts. We identify several interesting
features at promoters, within transcripts and in terminators relating
to transcription initiation, elongation, and termination. Furthermore,
we identify many putative non-coding transcripts.CONCLUSIONS:We provide
a global analysis of a cyanobacterial transcriptome. Our results
uncover insights that reinforce and extend the current views of bacterial
transcription.},
doi = {10.1186/gb-2011-12-5-r47},
issn = {1465-6906},
pubmedid = {21612627},
url = {http://genomebiology.com/2011/12/5/R47}
}
@ARTICLE{Vijayan2009,
author = {Vijayan, Vikram and Zuzow, Rick and O'Shea, Erin K.},
title = {Oscillations in supercoiling drive circadian gene expression in cyanobacteria},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {22564--22568},
number = {52},
month = dec,
abstract = {The cyanobacterium Synechococcus elongatus PCC 7942 exhibits oscillations
in mRNA transcript abundance with 24-h periodicity under continuous
light conditions. The mechanism underlying these oscillations remains
elusive--neither cis nor trans-factors controlling circadian gene
expression phase have been identified. Here, we show that the topological
status of the chromosome is highly correlated with circadian gene
expression state. We also demonstrate that DNA sequence characteristics
of genes that appear monotonically activated and monotonically repressed
by chromosomal relaxation during the circadian cycle are similar
to those of supercoiling-responsive genes in Escherichia coli. Furthermore,
perturbation of superhelical status within the physiological range
elicits global changes in gene expression similar to those that occur
during the normal circadian cycle.},
url = {http://www.pnas.org/cgi/content/abstract/106/52/22564}
}
@ARTICLE{Vik-Mo2009,
author = {Vik-Mo, Audun and Fernø, Johan and Skrede, Silje and Steen, Vidar},
title = {Psychotropic drugs up-regulate the expression of cholesterol transport
proteins including ApoE in cultured human CNS- and liver cells},
journal = {BMC Pharmacology},
year = {2009},
volume = {9},
pages = {10},
number = {1},
abstract = {BACKGROUND:Disturbances in lipid homeostasis and myelination have
been proposed in the pathophysiology of schizophrenia and bipolar
disorder. We have previously shown that several antipsychotic and
antidepressant drugs increase lipid biosynthesis through activation
of the Sterol Regulatory Element-Binding Protein (SREBP) transcription
factors, which control the expression of numerous genes involved
in fatty acid and cholesterol biosynthesis. The aim of the present
proof-of-principle study was to investigate whether such drugs also
affect lipid transport and export pathways in cultured human CNS
and liver cells.RESULTS:Quantitative PCR and immunoblotting were
used to determine the level of lipid transport genes in human glioblastoma
(GaMg) exposed to clozapine, olanzapine, haloperidol or imipramine.
The effect of some of these drugs was also investigated in human
astrocytoma (CCF-STTG1), neuroblastoma (SH-SY5Y) and hepatocellular
carcinoma (HepG2) cells. We found significant transcriptional changes
of cholesterol transport genes (ApoE, ABCA1, NPC1, NPC2, NPC1L1),
which are predominantly controlled by the Liver X receptor (LXR)
transcription factor. The up-regulation was observed after 24 to
48 hours of drug exposure, which is markedly delayed as compared
to the drug-induced SREBP-controlled stimulation of lipid biosynthesis
seen after 6 hours.CONCLUSION:Our data show that stimulation of cellular
lipid biosynthesis by amphiphilic psychotropic drugs is followed
by a transcriptional activation of cholesterol transport and efflux
pathways. Such effects may be relevant for both therapeutic effects
and metabolic adverse effects of psychotropic drugs.},
doi = {10.1186/1471-2210-9-10},
issn = {1471-2210},
pubmedid = {19715613},
url = {http://www.biomedcentral.com/1471-2210/9/10}
}
@ARTICLE{Vik-Mo2010,
author = {Vik-Mo, Einar Osland and Sandberg, Cecilie and Olstorn, Havard and
Varghese, Mercy and Brandal, Petter and Ramm-Pettersen, Jon and Murrell,
Wayne and Langmoen, Iver Arne},
title = {Brain tumor stem cells maintain overall phenotype and tumorigenicity
after in vitro culturing in serum-free conditions},
journal = {Neuro Oncology},
year = {2010},
volume = {12},
pages = {1220--1230},
number = {12},
month = dec,
abstract = {Traditional in vitro culturing of tumor cells has been shown to induce
changes so that cultures no longer represent the tumor of origin.
Serum-free culturing conditions are used in a variety of cancers
to propagate stem-like cells in vitro. Limited reports, however,
exist on the effects of such propagation. We have compared cells
from brain tumor biopsies cultivated under serum-free conditions
at passages 2 and 10 to describe the effects of in vitro culturing.
We were able to establish cell lines from 7 of 10 biopsies from patients
with glioblastoma. The cell lines adapted to conditions and had 2.2
times increased population doubling rate at later passages. Karyotyping
and comparative genomic hybridization analysis revealed that all
examined cell lines had cytogenetic aberrations commonly found in
glioblastomas, and there were only minor differences between tumor
and early and late passages in the same culture. Whole-transcriptome
analysis shows that tumors had interindividual differences. Changes
in the overall expression patterns through passaging were modest,
with a significant change in only 14 genes; the variation among cultures
was, however, reduced through passages. The ability to differentiate
differed among tumors but was maintained throughout passaging. The
cells initiated tumors upon transplantation to immunodeficient mice
with differing phenotypes, but a given cell culture maintained tumor
phenotype after serial cultivation. The cultures established maintained
individual characteristics specific to culture identity. Thus, each
cell culture reflects an image of the tumor--or a personalized model--from
which it was derived and remains representative after moderate expansion.},
comment = {10.1093/neuonc/noq102},
url = {http://neuro-oncology.oxfordjournals.org/cgi/content/abstract/12/12/1220}
}
@ARTICLE{Vikman2006,
author = {Vikman, P. and Edvinsson, L.},
title = {Gene expression profiling in the human middle cerebral artery after
cerebral ischemia},
journal = {European Journal of Neurology},
year = {2006},
volume = {13},
pages = {1324--1332},
number = {12},
abstract = {We have investigated the gene expression in human middle cerebral
artery (MCA) after ischemia. Ischemic stroke affects the perfusion
in the affected area and experimental cerebral ischemia results in
upregulation of vasopressor receptors in the MCA leading to the ischemic
area. We obtained human MCA samples distributing to the ischemic
area, 7–10 days post-stroke. The gene expression was examined
with real-time polymerase chain reaction (PCR) and microarray, proteins
were studied with immunohistochemistry.We investigated genes previously
shown to be upregulated in animal models of cerebral ischemia (e.g.
ETA, ETB, AT1, AT2, and 5-HT2A/1B/1D). Their mRNA expression was
increased compared with controls, consistent with findings in experimental
stroke. Immunohistochemistry showed upregulation of the receptors
localized on the smooth muscle cells. The gene expression was profiled
with microarray and seven genes chosen for further investigation
with real-time PCR; ELK3, LY64, Metallothionin IG, POU3F4, Actinα2,
RhoA and smoothelin. Six of these were regulated the same way when
confirming array expression with real-time PCR. Gene expression studies
in the human MCA leading to the ischemic region is similar to that
seen after MCA occlusion in rats. We found new genes that support
the dynamic changes that occur in the MCA distributing to the ischemic
region.},
issn = {1468-1331},
keywords = {gene expression, human, ischemic stroke, MCA, receptors},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1468-1331.2006.01496.x}
}
@ARTICLE{Vikram2011,
author = {Vikram, Amit and Jesudhasan, Palmy R. and Jayaprakasha, G.K. and
Pillai, Suresh D. and Jayaraman, Arul and Patil, Bhimanagouda S.},
title = {Citrus flavonoid represses Salmonella pathogenicity island 1 and
motility in S. Typhimurium LT2},
journal = {International Journal of Food Microbiology},
year = {2011},
volume = {145},
pages = {28--36},
number = {1},
month = jan,
abstract = {Salmonellosis is one of the leading health problems worldwide. With
the rise of drug resistance strains, it has become imperative to
identify alternative strategies to counter bacterial infection. Natural
products were used historically to identify novel compounds with
various bioactivities. Citrus species is a rich source of flavonoids.
Naringenin, a flavonone, is present predominantly in grapefruit.
Previously we have demonstrated that naringenin is potent inhibitor
of cell-cell signaling. The current study was undertaken to understand
the effect of naringenin on Salmonella Typhimurium LT2. The cDNA
microarrays were employed to study the response of S. Typhimurium
to naringenin treatment. Naringenin specifically repressed 24 genes
in the Salmonella pathogenicity island 1 and down-regulated 17 genes
involved in flagellar and motility. Furthermore, phenotypic assays
support the result of microarray analysis. In addition, naringenin
seems to repress SPI-1 in pstS/hilD-dependent manner. Altogether
the data suggest that naringenin attenuated S. Typhimurium virulence
and cell motility. This is the first molecular evidence to demonstrate
effect of naringenin on bacterial virulence and cell motility.},
issn = {0168-1605},
keywords = {Citrus, Flavonoids, Microarray, SPI1, Flagellar operon, Virulence,
Adhesion},
url = {http://www.sciencedirect.com/science/article/pii/S0168160510006264}
}
@ARTICLE{Vilain2003,
author = {Vilain, Catheline and Libert, Frederick and Venet, David and Costagliola,
Sabine and Vassart, Gilbert},
title = {Small amplified RNA-SAGE: an alternative approach to study transcriptome
from limiting amount of mRNA},
journal = {Nucleic Acids Res.},
year = {2003},
volume = {31},
pages = {e24--},
number = {6},
month = mar,
abstract = {Serial analysis of gene expression (SAGE) is a widely used and powerful
technique to characterize and compare transcriptomes. Although several
modifications have been proposed to the initial protocol with the
aim of reducing the amount of starting material, unless additional
PCR steps are added, the technique is still limited by the need for
at least 1 {micro}g of total RNA. As extra PCR amplification might
introduce representation biases, current SAGE protocols are not fully
suitable for the study of small, microdissected tissue samples. We
propose here an alternative method involving the linear amplification
of small mRNA fragments containing the SAGE tags. The procedure allows
preparation of libraries of over 100 000 tags from as few as 2500
cells. A satisfactory correlation was observed between a microSAGE
library made from 5 {micro}g of total thyroid RNA, and a library
prepared from 50 ng of the same RNA preparation according to the
present protocol.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/31/6/e24}
}
@ARTICLE{Vilalta2009,
author = {Vilalta, Adrián and Shlapobersky, Mark and Wei, Qun and Planchon,
Rodrick and Rolland, Alain and Sullivan, Sean},
title = {Analysis of biomarkers after intramuscular injection of Vaxfectin®-formulated
hCMV gB plasmid DNA},
journal = {Vaccine},
year = {2009},
volume = {27},
pages = {7409--7417},
number = {52},
month = dec,
abstract = {Cationic lipids have been used as delivery systems to enhance the
performance of vaccines and immunotherapeutics. However, little is
known about the effect of administration of cationic lipid-formulated
vaccines on gene expression. This study used DNA microarrays (39,000
transcripts) to characterize early changes in gene expression patterns
in mouse muscle 1 and 2 days after intramuscular (IM) injection of
a hCMV gB plasmid DNA (pDNA) vaccine formulated with the cationic
lipid system Vaxfectin®; gene expression profiles were compared to
those obtained after IM injection of pDNA in PBS. Analysis of the
DNA microarray data indicated that approximately 1% of the represented
transcripts were modulated at least 2-fold compared to the PBS samples
at both time points. Functional analysis of the modulated genes revealed
that transcripts involved in antigen processing and presentation,
apoptosis and the Toll-like receptor pathway were significantly enriched.
In addition, confirmation of local and systemic modulation of subsets
of biomarkers was achieved using Real-Time PCR and Cytometric Bead
Assays. Time course and magnitude of cellular infiltration (F4/80+
and CD11b+ cells) to the injection site was changed in response to
formulation of hCMVgB pDNA with Vaxfectin®. Since the expression
level of the pDNA-encoded transgene in the muscle was not affected
by formulation Vaxfectin® mechanism of action is expected to rely
primarily on modulation of immune pathways and not on an increase
in transfection of the antigen-encoding pDNA. Taken together, these
data help explain the Vaxfectin®-dependent robust enhancement of
immune responses.},
issn = {0264-410X},
keywords = {pDNA vaccine, CMV, Cationic lipid adjuvant, Biomarker},
url = {http://www.sciencedirect.com/science/article/B6TD4-4X8HGSJ-1/2/d21cadbf60c4b6aab55053cfe9ad9ea7}
}
@ARTICLE{Vilar2011,
author = {Vilar, Eduardo and Bartnik, Catherine M. and Stenzel, Stephanie L.
and Raskin, Leon and Ahn, Jaeil and Moreno, Victor and Mukherjee,
Bhramar and Iniesta, Maria D. and Morgan, Meredith A. and Rennert,
Gad and Gruber, Stephen B.},
title = {MRE11 Deficiency Increases Sensitivity to Poly(ADP-ribose) Polymerase
Inhibition in Microsatellite Unstable Colorectal Cancers},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {2632--2642},
number = {7},
month = apr,
abstract = {Microsatellite instability (MSI) is displayed by approximately 15%
of colorectal cancers (CRC). Defective DNA mismatch repair generates
mutations at repetitive DNA sequences such as those located in the
double strand break (DSB) repair gene MRE11. We assessed the mutational
status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors
and found a strong correlation with MSI status in both cell lines
and tumors. Therefore, we hypothesized that deficiency in MRE11 may
sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition
based on the concept of synthetic lethality. We further assessed
the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines
and observed preferential cytotoxicity in those MSI cell lines harboring
mutations in MRE11 compared with both wild-type cell lines and microsatellite
stable (MSS) cell lines. A significant correlation between MRE11
expression levels and cytotoxicity to ABT-888 at 10 {micro}M was
observed (R2 = 0.915, P < 0.001). Using two experimental approaches,
including short hairpin RNA knocking down MRE11 in the wild-type
and MSS cell line SW-480 and a second cell line model transfected
with mutant MRE11, we experimentally tried to confirm the role of
MRE11 in conferring sensitivity to PARP-1 inhibition. Both models
led to changes in proliferation in response to ABT-888 at different
concentrations, and a drug-response effect was not observed, suggesting
a possible contribution of additional genes. We conclude that MSI
colorectal tumors deficient in DSB repair secondary to mutation in
MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical
investigation of PARP-1 inhibitors is warranted in MSI CRCs. Cancer
Res; 71(7); 2632-42. (C)2011 AACR.},
comment = {10.1158/0008-5472.CAN-10-1120},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/7/2632}
}
@ARTICLE{Vilches2009,
author = {Vilches, Silvia and Jimenez, Natalia and Tomas, Juan M. and Merino,
Susana},
title = {Aeromonas hydrophila AH-3 Type III Secretion System Expression and
Regulatory Network},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {6382--6392},
number = {19},
month = oct,
abstract = {The Aeromonas hydrophila type III secretion system (T3SS) has been
shown to play a crucial role in this pathogen's interactions with
its host. We previously described the genetic organization of the
T3SS cluster and the existence of at least one effector, called AexT,
in A. hydrophila strain AH-3. In this study, we analyzed the expression
of the T3SS regulon by analyzing the activity of the aopN-aopD and
aexT promoters (T3SS machinery components and effector, respectively)
by means of two different techniques: promoterless gfp fusions and
real-time PCR. The expression of the A. hydrophila AH-3 T3SS regulon
was induced in response to several environmental factors, of which
calcium depletion, a high magnesium concentration, and a high growth
temperature were shown to be the major ones. Once the optimal conditions
were established, we tested the expression of the T3SS regulon in
the background of several virulence determinant knockouts of strain
AH-3. The analysis of the data obtained from axsA and aopN mutants,
both of which have been described to be T3SS regulators in other
species, allowed us to corroborate their function as the major transcription
regulator and valve of the T3SS, respectively, in Aeromonas hydrophila.
We also demonstrated the existence of a complicated interconnection
between the expression of the T3SS and several other different virulence
factors, such as the lipopolysaccharide, the PhoPQ two-component
system, the ahyIR quorum sensing system, and the enzymatic complex
pyruvate deshydrogenase. To our knowledge, this is the first study
of the A. hydrophila T3SS regulatory network.},
url = {http://aem.asm.org/cgi/content/abstract/75/19/6382}
}
@ARTICLE{VilchA¨ze2010,
author = {Vilchèze, Catherine and Weinrick, Brian and Wong, Ka-Wing and Chen,
Bing and Jacobs, Jr, William R.},
title = {NAD+ auxotrophy is bacteriocidal for the tubercle bacilli},
journal = {Molecular Microbiology},
year = {2010},
volume = {76},
pages = {365--377},
number = {2},
abstract = {Summary The human tubercle bacillus Mycobacterium tuberculosis can
synthesize NAD+ using the de novo biosynthesis pathway or the salvage
pathway. The salvage pathway of the bovine tubercle bacillus Mycobacterium
bovis was reported defective due to a mutation in the nicotinamidase
PncA. This defect prevents nicotinic acid secretion, which is the
basis for the niacin test that clinically distinguishes M. bovis
from M. tuberculosis. Surprisingly, we found that the NAD+de novo
biosynthesis pathway (nadABC) can be deleted from M. bovis, demonstrating
a functioning salvage pathway. M. bovisΔnadABC fails to grow in
mice, whereas M. tuberculosisΔnadABC grows normally in mice, suggesting
that M. tuberculosis can acquire nicotinamide from its host. The
introduction of M. tuberculosis pncA into M. bovisΔnadABC is sufficient
to fully restore growth in a mouse, proving that the functional salvage
pathway enables nicotinamide acquisition by the tubercle bacilli.
This study demonstrates that NAD+ starvation is a cidal event in
the tubercle bacilli and confirms that enzymes common to the de novo
and salvage pathways may be good drug targets.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07099.x}
}
@ARTICLE{Villanueva2011,
author = {Villanueva, Eneida and Yalavarthi, Srilakshmi and Berthier, Celine
C. and Hodgin, Jeffrey B. and Khandpur, Ritika and Lin, Andrew M.
and Rubin, Cory J. and Zhao, Wenpu and Olsen, Stephen H. and Klinker,
Matthew and Shealy, David and Denny, Michael F. and Plumas, Joel
and Chaperot, Laurence and Kretzler, Matthias and Bruce, Allen T.
and Kaplan, Mariana J.},
title = {Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues,
and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {538-552},
number = {1},
abstract = {An abnormal neutrophil subset has been identified in the PBMC fractions
from lupus patients. We have proposed that these low-density granulocytes
(LDGs) play an important role in lupus pathogenesis by damaging endothelial
cells and synthesizing increased levels of proinflammatory cytokines
and type I IFNs. To directly establish LDGs as a distinct neutrophil
subset, their gene array profiles were compared with those of autologous
normal-density neutrophils and control neutrophils. LDGs significantly
overexpress mRNA of various immunostimulatory bactericidal proteins
and alarmins, relative to lupus and control neutrophils. In contrast,
gene profiles of lupus normal-density neutrophils do not differ from
those of controls. LDGs have heightened capacity to synthesize neutrophils
extracellular traps (NETs), which display increased externalization
of bactericidal, immunostimulatory proteins, and autoantigens, including
LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity
to kill endothelial cells and to stimulate IFN- synthesis by plasmacytoid
dendritic cells. Affected skin and kidneys from lupus patients are
infiltrated by netting neutrophils, which expose LL-37 and dsDNA.
Tissue NETosis is associated with increased anti-dsDNA in sera. These
results expand the potential pathogenic roles of aberrant lupus neutrophils
and suggest that dysregulation of NET formation and its subsequent
responses may play a prominent deleterious role.},
doi = {10.4049/jimmunol.1100450},
eprint = {http://www.jimmunol.org/cgi/reprint/187/1/538.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/1/538}
}
@ARTICLE{Villar2011,
author = {Villar, Emilie and Klopp, Christophe and Noirot, Celine and Novaes,
Evandro and Kirst, Matias and Plomion, Christophe and Gion, Jean-Marc},
title = {RNA-Seq reveals genotype-specific molecular responses to water deficit
in eucalyptus},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {538},
number = {1},
abstract = {BACKGROUND:In a context of climate change, phenotypic plasticity provides
long-lived species, such as trees, with the means to adapt to environmental
variations occurring within a single generation. In eucalyptus plantations,
water availability is a key factor limiting productivity. However,
the molecular mechanisms underlying the adaptation of eucalyptus
to water shortage remain unclear. In this study, we compared the
molecular responses of two commercial eucalyptus hybrids during the
dry season. Both hybrids differ in productivity when grown under
water deficit.RESULTS:Pyrosequencing of RNA extracted from shoot
apices provided extensive transcriptome coverage - a catalog of 129,993
unigenes (49,748 contigs and 80,245 singletons) was generated from
398 million base pairs, or 1.14 million reads. The pyrosequencing
data enriched considerably existing Eucalyptus EST collections, adding
36,985 unigenes not previously represented. Digital analysis of read
abundance in 14,460 contigs identified 1,280 that were differentially
expressed between the two genotypes, 155 contigs showing differential
expression between treatments (irrigated vs. non irrigated conditions
during the dry season), and 274 contigs with significant genotype-by-treatment
interaction. The more productive genotype displayed a larger set
of genes responding to water stress. Moreover, stress signal transduction
seemed to involve different pathways in the two genotypes, suggesting
that water shortage induces distinct cellular stress cascades. Similarly,
the response of functional proteins also varied widely between genotypes:
the most productive genotype decreased expression of genes related
to photosystem, transport and secondary metabolism, whereas genes
related to primary metabolism and cell organisation were over-expressed.CONCLUSIONS:For
the most productive genotype, the ability to express a broader set
of genes in response to water availability appears to be a key characteristic
in the maintenance of biomass growth during the dry season. Its strategy
may involve a decrease of photosynthetic activity during the dry
season associated with resources reallocation through major changes
in the expression of primary metabolism associated genes. Further
efforts will be needed to assess the adaptive nature of the genes
highlighted in this study.},
doi = {10.1186/1471-2164-12-538},
issn = {1471-2164},
pubmedid = {22047139},
url = {http://www.biomedcentral.com/1471-2164/12/538}
}
@ARTICLE{Villeneuve2007,
author = {Villeneuve, Daniel L. and Blake, Lindsey S. and Brodin, Jeffrey D.
and Greene, Katie J. and Knoebl, Iris and Miracle, Ann L. and Martinovic,
Dalma and Ankley, Gerald T.},
title = {Transcription of Key Genes Regulating Gonadal Steroidogenesis in
Control and Ketoconazole- or Vinclozolin-Exposed Fathead Minnows},
journal = {Toxicol. Sci.},
year = {2007},
volume = {98},
pages = {395--407},
number = {2},
month = aug,
abstract = {This study evaluated changes in the expression of steroidogenesis-related
genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin
(VZ) for 21 days. The aim was to evaluate links between molecular
changes and higher level outcomes after exposure to endocrine-active
chemicals (EACs) with different modes of action. To aid our analysis
and interpretation of EAC-related effects, we first examined variation
in the relative abundance of steroidogenesis-related gene transcripts
in the gonads of male and female fathead minnows as a function of
age, gonad development, and spawning status, independent of EAC exposure.
Gonadal expression of several genes varied with age and/or gonadal
somatic index in either males or females. However, with the exception
of aromatase, steroidogenesis-related gene expression did not vary
with spawning status. Following the baseline experiments, expression
of the selected genes in male fathead minnows exposed to KTC or VZ
was evaluated in the context of effects observed at higher levels
of organization. Exposure to KTC elicited changes in gene transcription
that were consistent with an apparent compensatory response to the
chemical's anticipated direct inhibition of steroidogenic enzyme
activity. Exposure to VZ, an antiandrogen expected to indirectly
impact steroidogenesis, increased pituitary expression of follicle-stimulating
hormone {beta}-subunit as well as testis expression of 20{beta}-hydroxysteroid
dehydrogenase and luteinizing hormone receptor transcripts. Results
of this study contribute to ongoing research aimed at understanding
responses of the teleost hypothalamic-pituitary-gonadal axis to different
types of EACs and how changes in molecular endpoints translate into
apical outcomes reflective of either adverse effect or compensation.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/98/2/395}
}
@ARTICLE{Villeneuve2012,
author = {Villeneuve, Daniel L. and Garcia-Reyero, Natà lia and Escalon, B.
Lynn and Jensen, Kathleen M. and Cavallin, Jenna E. and Makynen,
Elizabeth A. and Durhan, Elizabeth J. and Kahl, Michael D. and Thomas,
Linnea M. and Perkins, Edward J. and Ankley, Gerald T.},
title = {Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study
with Bisphenol A in Fish},
journal = {Environmental Science \& Technology},
year = {2012},
volume = {46},
pages = {51-59},
number = {1},
abstract = { Effects of bisphenol A (BPA) on ovarian transcript profiles as well
as targeted end points with endocrine/reproductive relevance were
examined in two fish species, fathead minnow (Pimephales promelas)
and zebrafish (Danio rerio), exposed in parallel using matched experimental
designs. Four days of waterborne exposure to 10 μg BPA/L caused
significant vitellogenin induction in both species. However, zebrafish
were less sensitive to effects on hepatic gene expression and steroid
production than fathead minnow and the magnitude of vitellogenin
induction was more modest (i.e., 3-fold compared to 13 000-fold
in fathead minnow). The concentration–response at the ovarian transcriptome
level was nonmonotonic and violated assumptions that underlie proposed
methods for estimating hazard thresholds from transcriptomic results.
However, the nonmonotonic profile was consistent among species and
there were nominal similarities in the functions associated with
the differentially expressed genes, suggesting potential activation
of common pathway perturbation motifs in both species. Overall, the
results provide an effective case study for considering the potential
application of ecotoxicogenomics to ecological risk assessments and
provide novel comparative data regarding effects of BPA in fish.
},
doi = {10.1021/es201150a},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/es201150a},
url = {http://pubs.acs.org/doi/abs/10.1021/es201150a}
}
@ARTICLE{Villeneuve2010,
author = {Villeneuve, Daniel L. and Garcia-Reyero, Natàlia and Martinovic,
Dalma and Cavallin, Jenna E. and Mueller, Nathaniel D. and Wehmas,
Leah C. and Kahl, Michael D. and Linnum, Anne L. and Perkins, Edward
J. and Ankley, Gerald T.},
title = {Influence of ovarian stage on transcript profiles in fathead minnow
(Pimephales promelas) ovary tissue},
journal = {Aquatic Toxicology},
year = {2010},
volume = {98},
pages = {354--366},
number = {4},
month = jul,
abstract = {Interpretation of toxicogenomic experiments conducted with ovary tissue
from asynchronous-spawning small fish species is complicated by background
variation in the relative abundance and proportion of follicles at
different stages within the ovary tissue sample. This study employed
both real-time quantitative polymerase chain reaction and a 15,000
gene oligonucleotide microarray to examine variation in the fathead
minnow (Pimephales promelas) ovarian transcriptional profile as a
function of quantitative and qualitative differences in ovarian histology.
The objectives were to provide data that could potentially aid interpretation
of future toxicogenomics experiments, identify putative stage-related
transcriptional markers, and generate insights into basic biological
regulation of asynchronous oocyte development. Multiple lines of
evidence from the present study indicate that variation in the transcriptional
profile is primarily dependent on the relative abundance of previtellogenic
versus vitellogenic follicles in the ovary. Due to the relatively
small proportions of mature ovulated follicles or atretic follicles
in the overall follicle population, few potential transcriptional
markers of maturation, ovulation, or atresia could be identified.
However, among the 460 differentially expressed genes identified
in the present study, several targets, including HtrA serine peptidase
3 (htra3), tissue inhibitor of metalloproteinase 3 (timp3), aquaporin
8 (aqp8), transgelin 2 like (tagln2), Nedd4 family interacting protein
2 (ndfip2), chemokine ligand 12a (cxcl12a), midkine-related growth
factor (mdka), and jagged 1b (jag 1b) exhibited responses and functional
properties that support them as candidate molecular markers of significant
shift in gross ovarian stage. Genes associated with a diversity of
functions including cellular development, morphogenesis, coated vesicle
transport, sexual reproduction, and neuron development, among others,
were statistically enriched within the list of 460 genes differentially
expressed among different ovarian classes. Overall, results of this
study provide insights into background variation in ovary transcript
profiles that should aid and enhance the interpretation of toxicogenomic
data generated in experiments conducted with small, asynchronous-spawning
fish species.},
issn = {0166-445X},
keywords = {Oogenesis, Toxicogenomics, Reproduction, Histology},
url = {http://www.sciencedirect.com/science/article/B6T4G-4YMB604-2/2/4120345eda9a5e895557ea79f2f75cea}
}
@ARTICLE{Villeneuve2010a,
author = {Villeneuve, Daniel L. and Garcia-Reyero, Natàlia and Martinovic,
Dalma and Mueller, Nathaniel D. and Cavallin, Jenna E. and Durhan,
Elizabeth J. and Makynen, Elizabeth A. and Jensen, Kathleen M. and
Kahl, Michael D. and Blake, Lindsey S. and Perkins, Edward J. and
Ankley, Gerald T.},
title = {II: Effects of a dopamine receptor antagonist on fathead minnow dominance
behavior and ovarian gene expression in the fathead minnow and zebrafish},
journal = {Ecotoxicology and Environmental Safety},
year = {2010},
volume = {73},
pages = {478--485},
number = {4},
month = may,
abstract = {Neurotransmitters such as dopamine play an important role in reproductive
behaviors and signaling. Neuroendocrine-active chemicals in the environment
have potential to interfere with and/or alter these processes. A
companion study with the dopamine 2 receptor antagonist, haloperidol,
found no evidence of a direct effect of the chemical on fish reproduction.
This study considered haloperidol's potential effects on behavior
and ovarian gene expression. Male fathead minnows exposed to 50 [mu]g
haloperidol/L for 96 h were found to be significantly more dominant
than control males. In terms of molecular signaling, investigated
using oligonucleotide microarrays, there was little similarity in
the identity and functions of genes differentially expressed in the
ovaries of fathead minnows (Pimephales promelas) versus zebrafish
(Danio rerio) exposed under the same conditions. Results suggest
that non-lethal concentrations of haloperidol do not induce ovarian
molecular responses that could serve as biomarkers of exposure to
D2R antagonists, but may impact behavior.},
issn = {0147-6513},
keywords = {Endocrine disruption, Microarray, Species comparison, Neurotransmitter,
Purine biosynthesis, Antipsychotic, Toxicogenomics, Neuroendocrine,
Ovary, Gonadotropins},
url = {http://www.sciencedirect.com/science/article/B6WDM-4XMTFJ9-1/2/dab900103583be120581f1c55fdee7e4}
}
@ARTICLE{Villeneuve2006,
author = {Villeneuve, Daniel L. and Knoebl, Iris and Kahl, Michael D. and Jensen,
Kathleen M. and Hammermeister, Dean E. and Greene, Katie J. and Blake,
Lindsey S. and Ankley, Gerald T.},
title = {Relationship between brain and ovary aromatase activity and isoform-specific
aromatase mRNA expression in the fathead minnow (Pimephales promelas)},
journal = {Aquatic Toxicology},
year = {2006},
volume = {76},
pages = {353--368},
number = {3-4},
month = mar,
abstract = {There is growing evidence that some chemicals present in the environment
have the capacity to inhibit, or potentially induce, aromatase activity.
This study compared aromatase activities and isoform-specific mRNA
expression in brain and ovary tissue from non-exposed fathead minnows
representing three different ages and stages of reproductive activity,
and from fathead minnows exposed to the aromatase inhibitor fadrozole
for 7 d. The goal was to determine whether measures of a single aromatase
endpoint in either brain or ovary tissue would be sufficient to understand
and predict system-wide effects of endocrine disrupting chemicals
on aromatase activity and transcript levels. Aromatase activity in
the ovary, but not brain, varied significantly with age/reproductive
category, with adults held in non-reproductive conditions showing
significantly lower activity than juveniles and reproductively-active
adults. Significant correlations between isoform-specific transcript
levels and aromatase activity were observed for ovary tissue, but
those relationships were not robust for all age/reproductive categories,
nor were they sustained in fadrozole-treated fish. In vitro, fadrozole
inhibited the aromatase activity of brain and ovary post-mitochondrial
supernatants with similar potency (IC50s = 8.82 ± 1.58 and 6.93 ± 0.80 [mu]M
for brain and ovary, respectively), despite large differences in
the magnitude of activity. In vivo, fadrozole altered aromatase activity
and isoform-specific transcript levels in both brain and ovary tissue,
but concentration-response relationships were different for each
tissue. Aromatase activity and P450aromB mRNA expression in brain
showed a dose-dependent decrease at concentrations greater than 5.55 [mu]g/L.
In contrast, ovary activity showed an inverted U-shaped concentration-response
consistent with the interplay between increased P450aromA transcript
levels in ovary and competitive inhibition of the aromatase enzyme.
As a whole, results of this study did not reveal any robust correlations
between brain and ovary aromatase activity and/or isoform-specific
mRNA expression. However, they were consistent with the current body
of evidence related to teleost aromatase regulation, suggesting that
increased understanding of the biology of aromatase may facilitate
system-wide understanding of effects on aromatase based on relatively
few measured endpoints.},
issn = {0166-445X},
keywords = {Aromatase inhibitor, Q-PCR, Real-time PCR, Fathead minnow, Fadrozole,
Reproduction},
url = {http://www.sciencedirect.com/science/article/B6T4G-4HPKBMC-1/2/012a29c6598613bddda0880a5b972d49}
}
@ARTICLE{Villeneuve2007a,
author = {Villeneuve, Daniel L. and Miracle, Ann L. and Jensen, Kathleen M.
and Degitz, Sigmund J. and Kahl, Michael D. and Korte, Joseph J.
and Greene, Katie J. and Blake, Lindsey S. and Linnum, Ann L. and
Ankley, Gerald T.},
title = {Development of quantitative real-time PCR assays for fathead minnow
(Pimephales promelas) gonadotropin [beta] subunit mRNAs to support
endocrine disruptor research},
journal = {Comparative Biochemistry and Physiology Part C: Toxicology \& Pharmacology},
year = {2007},
volume = {145},
pages = {171--183},
number = {2},
month = mar,
abstract = {Fathead minnows (Pimephales promelas) are a widely-used small fish
model for regulatory ecotoxicology testing and research related to
endocrine disrupting chemicals (EDCs). Quantitative real-time PCR
assays for measuring fathead minnow gonadotropin (GtH) [beta] subunit
transcripts were developed and "baseline" transcript levels in pituitary
tissue were examined over a range of age classes and spawning states.
Among females, GtH[beta] transcripts did not vary significantly with
gonadal-somatic index or gonad stage. However, in males, follicle-stimulating
hormone [beta] subunit transcripts decreased significantly with increasing
gonad stage, while mean luteinizing hormone [beta] subunit expression
trended in the opposite direction. GtH[beta] transcript levels measured
in pituitaries from fish that had spawned within the preceding 24 h
were not significantly different from those from fish that were 2-3 days
post-spawn. Exposure to the fungicide ketoconazole, a known steroidogenesis
inhibitor, for 21 days significantly affected the abundance of GtH[beta]
transcripts in pituitary tissue in males, but not females. This study
provides critical data needed to design and interpret effective experiments
for studying direct and indirect effects of EDCs on GtH subunit mRNA
expression. Results of such experiments should facilitate a greater
understanding of integrated system-wide responses of the fathead
minnow brain-pituitary-gonadal axis to stressors including EDCs.},
issn = {1532-0456},
keywords = {Luteinizing hormone, Follicle-stimulating hormone, Ketoconazole, Reproduction,
Spawning, Gonad development, cDNA sequence},
url = {http://www.sciencedirect.com/science/article/B6W89-4MDP83C-1/2/34bfad959bcaaaf5e5b1547e7e941b5a}
}
@ARTICLE{Villeneuve2008,
author = {Villeneuve, Jérôme and Galarneau, Hugo and Beaudet, Marie-Josée
and Tremblay, Pierrot and Chernomoretz, Ariel and Vallières, Luc},
title = {Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin
2 Treatment},
journal = {Brain Pathology},
year = {2008},
volume = {18},
pages = {401--414},
number = {3},
abstract = {Abstract All patients with glioblastoma, the most aggressive and common
form of brain cancer, develop cerebral edema. This complication is
routinely treated with dexamethasone, a steroidal anti-inflammatory
drug whose effects on brain tumors are not fully understood. Here
we show that dexamethasone can reduce glioma growth in mice, even
though it depletes infiltrating T cells with potential antitumor
activity. More precisely, T cells with helper or cytotoxic function
were sensitive to dexamethasone, but not those that were negative
for the CD4 and CD8 molecules, including gammadelta and natural killer
(NK) T cells. The antineoplastic effect of dexamethasone was indirect,
as it did not meaningfully affect the growth and gene expression
profile of glioma cells in vitro. In contrast, hundreds of dexamethasone-modulated
genes, notably angiopoietin 2 (Angpt2), were identified in cultured
cerebral endothelial cells by microarray analysis. The ability of
dexamethasone to attenuate Angpt2 expression was confirmed in vitro
and in vivo. Selective neutralization of Angpt2 using a peptide-Fc
fusion protein reduced glioma growth and vascular enlargement to
a greater extent than dexamethasone, without affecting T cell infiltration.
In conclusion, this study suggests a mechanism by which dexamethasone
can slow glioma growth, providing a new therapeutic target for malignant
brain tumors.},
issn = {1750-3639},
keywords = {angiopoietin-2, antitumor immunity, gene profiling, glioblastoma,
glucocorticoid, tumor endothelium},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x}
}
@ARTICLE{Vinas2008,
author = {Vinas, Jordi and Piferrer, Francesc},
title = {Stage-Specific Gene Expression During Fish Spermatogenesis as Determined
by Laser-Capture Microdissection and Quantitative-PCR in Sea Bass
(Dicentrarchus labrax) Gonads},
journal = {Biol Reprod},
year = {2008},
volume = {79},
pages = {738--747},
number = {4},
month = oct,
abstract = {The role of genes implicated in the regulation of spermatogenesis
and their patterns of expression is still poorly understood. In this
study, we took advantage of the cystic arrangement of the teleost
testis to set up a laser capture microdissection procedure to isolate
cells from cysts containing spermatogonia, spermatocytes, spermatids,
or spermatozoa. We then used quantitative PCR to determine the stage-specific
expression patterns of the germ cell marker vasa; gonadal aromatase
(cyp19a); estrogen receptors (ers) alpha, beta1, and beta2 (era,
erb1, and erb2, respectively); 11beta-hydroxylase (cyp11b1); androgen
receptor beta (arb); insulinlike growth factor 1 (igf1); and sox17.
vasa had the highest mRNA levels, followed by genes involved in androgen
metabolism (cyp11b1 and arb). Most genes associated with estrogen
metabolism (cyp19a, era, and erb1) had a lower expression, whereas
igf1 and sox17 exhibited the lowest mRNA levels. Comparison of changes
in mRNA levels revealed five patterns of gene expression, in general
with progressively lower expression seen as spermatogenesis advanced.
igf1 and sox17 were exclusively expressed in spermatogonia-containing
cysts, suggesting effects during the proliferative stage. Genes involved
in androgen synthesis (cyp11b1) and action (arb) peaked during the
early stages of spermatogenesis and then sharply decreased. In contrast,
genes associated with estrogen action, particularly erb2 and era,
showed a more gradual decrease. Together, these results demonstrate
the usefulness of fish models and suggest that whereas androgens
are required at high levels and may exert their major actions at
the initial stages of spermatogenesis, estrogens are also essential,
albeit required at lower levels, and with a more generalized influence.},
url = {http://www.biolreprod.org/cgi/content/abstract/79/4/738}
}
@ARTICLE{Vinas2010,
author = {Vinas, Jose Luis and Sola, Anna and Jung, Michaela and Mastora, Chrysoula
and Vinuesa, Eugenia and Pi, Felip and Hotter, Georgina},
title = {Inhibitory action of Wnt target gene osteopontin on mitochondrial
cytochrome c release determines renal ischemic resistance},
journal = {Am J Physiol Renal Physiol},
year = {2010},
volume = {299},
pages = {F234--242},
number = {1},
month = jul,
abstract = {Certain determinants of ischemic resistance in the Brown Norway rat
strain have been proposed, but no studies to date have focused on
the role of the Wnt pathway in the ischemic resistance mechanism.
We performed a comparative genomic study in Brown Norway vs. Sprague-Dawley
rats. Selective manipulations of the Wnt pathway in vivo and in vitro
allowed us to study whether the action of the Wnt pathway on apoptosis
through the regulation of osteopontin was critical to the maintenance
of inherent ischemic resistance mechanisms. The results revealed
a major gene upregulation of the Wnt family in Brown Norway rats
after renal ischemia-reperfusion. Manipulation of the Wnt signaling
cascade by selective antibodies increased mitochondrial cytochrome
c release and caspase 3 activity. The antiapoptotic role of Wnt was
mediated by osteopontin, a direct Wnt target gene. Osteopontin was
reduced by Wnt antibody administration in vivo, and osteopontin gene
silencing in vitro significantly increased mitochondrial cytochrome
c release. The overexpression of Wnt pathway genes detected in Brown
Norway rats is critical in the maintenance of their inherent ischemic
resistance. Activation of the Wnt signaling cascade reduces mitochondrial
cytochrome c release and caspase 3 activity through the action of
osteopontin.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/299/1/F234}
}
@ARTICLE{Vinatzer2005,
author = {Vinatzer, Ursula and Dampier, Brigitta and Streubel, Berthold and
Pacher, Margit and Seewald, Michael J. and Stratowa, Christian and
Kaserer, Klaus and Schreiber, Martin},
title = {Expression of HER2 and the Coamplified Genes GRB7 and MLN64 in Human
Breast Cancer: Quantitative Real-time Reverse Transcription-PCR as
a Diagnostic Alternative to Immunohistochemistry and Fluorescence
In situ Hybridization},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {8348--8357},
number = {23},
month = dec,
abstract = {Purpose: Accurate testing of HER2 is centrally important for breast
cancer therapy and prognosis. Immunohistochemistry (IHC) and fluorescence
in situ hybridization (FISH) are current standard testing methods.
As a potential alternative for assessment of HER2, we explored quantitative
real-time reverse transcription-PCR (RT-PCR), a fast and inexpensive
method yielding quantitative results insensitive to interobserver
variability and amenable to standardized scoring. Experimental Design:
We assessed HER2 status at the DNA, mRNA, and protein levels with
FISH, quantitative RT-PCR, and IHC in 136 tumor samples from 85 breast
cancer patients. Expression of GRB7, MLN64, and p21, genes coregulated
with HER2, was also quantified with quantitative RT-PCR and correlated
with the overall survival (OS) and disease-free survival (DFS) individually
and in combination with HER2. Results: Twenty-nine percent and 19%
of the patients scored HER2 positive with IHC and quantitative RT-PCR,
respectively. In 18 of 19 cases, HER2 statuses in tumors and lymph
node metastases were identical. HER2 status significantly correlated
with DFS when determined by IHC (P < 0.01), quantitative RT-PCR (P
< 0.003), but not with FISH (P = 0.09). The combination of HER2 with
MLN64, but not with GRB7 or p21, enhanced the prognostic power for
the DFS (P < 0.00005) and OS (P < 0.0008). Conclusions: Quantitative
RT-PCR seems to be clinically as useful in the assessment of HER2
status as IHC and FISH, yielding comparable correlations of HER2
status with the OS and DFS. Thus, quantitative RT-PCR analysis of
HER2 or HER2 plus MLN64 is a promising complement or alternative
to current methods for HER2 testing, particularly in laboratories
lacking FISH or IHC technology.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/23/8348}
}
@ARTICLE{Vinatzer2008,
author = {Vinatzer, Ursula and Gollinger, Michaela and Mullauer, Leonhard and
Raderer, Markus and Chott, Andreas and Streubel, Berthold},
title = {Mucosa-Associated Lymphoid Tissue Lymphoma: Novel Translocations
Including Rearrangements of ODZ2, JMJD2C, and CNN3},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {6426--6431},
number = {20},
month = oct,
abstract = {Purpose: The well-known translocations identified in MALT lymphomas
include t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, and t(14;18)/IGH-MALT1.
Molecular investigations have suggested that these three disparate
translocations affect a common pathway, resulting in the constitutive
activation of nuclear factor-{kappa}B. However, the vast majority
of MALT lymphomas are negative for any of the above-mentioned translocations
and the underlying pathogenesis is unclear. Experimental Design:
Fresh tissue of 29 gastric and extragastric MALT lymphomas was studied
for genetic aberrations by conventional karyotyping, long-distance
inverse PCR (LDI-PCR), fluorescence in situ hybridization (FISH),
reverse transcription-PCR (RT-PCR), and real-time quantitative RT-PCR
(QRT-PCR). Results: Conventional cytogenetics, FISH, and RT-PCR identified
aberrations in 26 of 29 MALT lymphoma. Balanced translocations were
found in 21 cases. IGH was rearranged in the majority of cases with
balanced translocations (n = 17/21); 3 cases had t(11;18)/API2-MALT1
and 1 case had novel t(6;7)(q25;q11), respectively. IGH partner genes
involved MALT1, FOXP1, BCL6, and four new chromosomal regions on
chromosome arms 1p, 1q, 5q, and 9p. LDI-PCR identified three novel
partner genes on 1p (CNN3), 5q (ODZ2), and 9p (JMJD2C). FISH assays
were established and confirmed LDI-PCR results. QRT-PCR showed deregulation
of the novel genes in the translocation-positive cases. Conclusions:
Our study expands the knowledge on the genetic heterogeneity of MALT
lymphomas.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/20/6426}
}
@ARTICLE{Vincent-Chong2011,
author = {Vincent-Chong, Vui King and Ismail, Siti Mazlipah and Abdul Rahman,
Zainal Ariff and Noor Akmal, Sharifah and Anwar, Arif and Padmaja
Jayaprasad, Pradeep and Ramanathan, Anand and Karen-Ng, Lee Peng
and Kallarakkal, Thomas George and Wan Mustafa, Wan Mahadzir and
Mannil, Thomas Abraham and Keng Kiong, Tay and Zain, Rosnah Binti},
title = {Genome Wide Analysis of Oral Squamous Cell Carcinomas Revealed Over
Expression of ISG15, Nestin and WNT11},
journal = {Oral Diseases},
year = {2011},
pages = {no--no},
abstract = {Background:  Multistep pathways and mechanisms are involved in the
development of oral cancer. Chromosomal alterations are one of the
key such mechanisms implicated oral carcinogenesis. Therefore this
study aims to determine the genomic copy number alterations (CNAs)
in oral squamous cell carcinoma (OSCC) using array comparative genomic
hybridization (aCGH) and in addition attempt to correlate CNAs with
modified gene expression.Materials and methods:  Genome wide screening
was performed on 15 OSCCs using high-density aCGH. On the basis of
pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped
to CNA regions were selected for further evaluation of their mRNA
expression using quantitative reverse transcriptase PCR (qRT-PCR).Results: 
CNAs were observed on multiple genomic regions, including amplifications
on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on
3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15
had the highest mRNA expression level with a 22.5 fold increase,
followed by Nestin with a 4.5 fold increase and WNT11 with a 2.5
fold increase.Conclusions:  This study has identified several major
CNAs in oral cancer genomes and indicated that this correlates with
over expression of the ISG15, WNT11 and Nestin genes.© 2011 John
Wiley & Sons A/S},
doi = {10.1111/j.1601-0825.2011.01894.x},
issn = {1601-0825},
keywords = {Oral cancer, array CGH, ISG15, Nestin, WNT11},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1601-0825.2011.01894.x}
}
@ARTICLE{Vinogradov2007,
author = {Vinogradov, Alexander E. and Anatskaya, Olga V.},
title = {Organismal complexity, cell differentiation and gene expression:
human over mouse},
journal = {Nucleic Acids Res.},
year = {2007},
volume = {35},
pages = {6350--6356},
number = {19},
month = oct,
abstract = {We present a molecular and cellular phenomenon underlying the intriguing
increase in phenotypic organizational complexity. For the same set
of human-mouse orthologous genes (11 534 gene pairs) and homologous
tissues (32 tissue pairs), human shows a greater fraction of tissue-specific
genes and a greater ratio of the total expression of tissue-specific
genes to housekeeping genes in each studied tissue, which suggests
a generally higher level of evolutionary cell differentiation (specialization).
This phenomenon is spectacularly more pronounced in those human tissues
that are more directly involved in the increase of complexity, longevity
and body size (i.e. it is reflected on the organismal level as well).
Genes with a change in expression breadth show a greater human-mouse
divergence of promoter regions and encoded proteins (i.e. the functional
genomics data are supported by the structural analysis). Human also
shows the higher expression of translation machinery. The upstream
untranslated regions (5'UTRs) of human mRNAs are longer than mouse
5'UTRs (even after correction for the difference in genome sizes)
and contain more uAUG codons, which suggest a more complex regulation
at the translational level in human cells (and agrees well with the
augmented cell specialization).},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/35/19/6350}
}
@ARTICLE{Viola2008,
author = {Viola, Giampietro and Fortunato, Elena and Cecconet, Laura and Del
Giudice, Laura and Dall'Acqua, Francesco and Basso, Giuseppe},
title = {Central role of mitochondria and p53 in PUVA-induced apoptosis in
human keratinocytes cell line NCTC-2544},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {227},
pages = {84--96},
number = {1},
month = feb,
abstract = {Despite strong evidence concerning the high efficiency of PUVA therapy
(psoralen plus UVA light), its mechanism of action has not yet been
fully elucidated. In this study, we have evaluated in a cell line
of human keratinocytes (NCTC-2544) the effects of two linear psoralen
derivatives, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP),
that are widely used in PUVA therapy and two angular derivatives,
Angelicin (ANG) and 4,6,4'-trymetyl angelicin (TMA). All derivatives
photoinduce cellular death, TMA being the most active compound. The
cell cycle analysis showed that the four derivatives induce, 24 h
after irradiation, a cell cycle arrest in G1 phase later followed
by massive apoptosis. The G1 arrest is correlated to an increase
in the expression of p21Waf1/Cip1, a protein associated with the
cell cycle block and apoptosis. Furthermore, treatment of NCTC-2544
resulted in p53 activation by 5-MOP, 8-MOP, and ANG but not TMA and
its phosphorylation at serine-15. The levels of p21Waf1/Cip1 paralleled
p53 protein staining pattern suggesting that p53 activation correlated
with p21Waf1/Cip1 induction. Simultaneous to p53 activation, psoralens
induced mitochondrial depolarization, cytochrome c release, mitochondrial
production of reactive oxygen species, as well as caspase-3 and -9
activation. Thus these results strongly indicate the necessity of
p53 activation and the induction of the apoptotic machinery downstream
of mitochondria.},
issn = {0041-008X},
keywords = {Psoralens, Apoptosis, PUVA therapy, Mitochondria, p53, Cell cycle},
url = {http://www.sciencedirect.com/science/article/B6WXH-4PW5XGM-3/2/7b34f7529473e1aa86394d10c1ecf9a4}
}
@ARTICLE{Viprey2008,
author = {Viprey, VF and Lastowska, MA and Corrias, MV and Swerts, K and Jackson,
MS and Burchill, SA},
title = {Minimal disease monitoring by QRT-PCR: guidelines for identification
and systematic validation of molecular markers prior to evaluation
in prospective clinical trials},
journal = {J. Pathol.},
year = {2008},
volume = {216},
pages = {245--252},
number = {2},
abstract = {Abstract 10.1002/path.2406.abs Real-time RT–PCR (QRT–PCR) is a
sensitive method for the detection of minimal disease (MD) and may
improve monitoring of disease status and stratification of patients
for therapy. Where tumour-specific mRNAs have not been identified,
the selection of which target(s) is(are) optimal for the detection
of MD remains a challenge. This reflects the heterogeneity of tumour
cells, the stability of mRNAs and low-level of transcription in cells
of the normal haemopoietic compartments. The aim of this study was
to establish for the first time guidelines for the systematic prioritization
of potential markers of MD detected by QRT–PCR prior to evaluation
in multicentre prospective clinical outcome studies. We combined
microarray analysis, ESTs gene expression profiles, improved probe-sets
sequence annotation, and previously described standard operating
procedures for QRT–PCR analysis to identify and prioritize potential
markers of MD. Using this methodology, we identified 49 potential
markers of MD in neuroblastoma (NB), of which 11 were associated
with neuronal function. We found that, in addition to TH, Phox2B
and DCX mRNA may be useful targets for the detection of MD in children
with NB. This same strategy could be exploited to select MD markers
of other solid tumours from the large number of potential targets
identified by microarray gene expression profiles. Copyright © 2008
Pathological Society of Great Britain and Ireland. Published by John
Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {real-time RT–PCR, microarrays, neuroblastoma, peripheral blood,
bone marrow, minimal residual disease},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2406}
}
@ARTICLE{Virtaneva2005,
author = {Virtaneva, Kimmo and Porcella, Stephen F. and Graham, Morag R. and
Ireland, Robin M. and Johnson, Claire A. and Ricklefs, Stacy M. and
Babar, Imran and Parkins, Larye D. and Romero, Romina A. and Corn,
G. Judson and Gardner, Don J. and Bailey, John R. and Parnell, Michael
J. and Musser, James M.},
title = {Longitudinal analysis of the group A Streptococcus transcriptome
in experimental pharyngitis in cynomolgus macaques},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {9014--9019},
number = {25},
month = jun,
abstract = {Identification of the genetic events that contribute to host-pathogen
interactions is important for understanding the natural history of
infectious diseases and developing therapeutics. Transcriptome studies
conducted on pathogens have been central to this goal in recent years.
However, most of these investigations have focused on specific end
points or disease phases, rather than analysis of the entire time
course of infection. To gain a more complete understanding of how
bacterial gene expression changes over time in a primate host, the
transcriptome of group A Streptococcus (GAS) was analyzed during
an 86-day infection protocol in 20 cynomolgus macaques with experimental
pharyngitis. The study used 260 custom Affymetrix (Santa Clara, CA)
chips, and data were confirmed by TaqMan analysis. Colonization,
acute, and asymptomatic phases of disease were identified. Successful
colonization and severe inflammation were significantly correlated
with an early onset of superantigen gene expression. The differential
expression of two-component regulators covR and spy0680 (M1_spy0874)
was significantly associated with GAS colony-forming units, inflammation,
and phases of disease. Prophage virulence gene expression and prophage
induction occurred predominantly during high pathogen cell densities
and acute inflammation. We discovered that temporal changes in the
GAS transcriptome were integrally linked to the phase of clinical
disease and host-defense response. Knowledge of the gene expression
patterns characterizing each phase of pathogen-host interaction provides
avenues for targeted investigation of proven and putative virulence
factors and genes of unknown function and will assist vaccine research.},
url = {http://www.pnas.org/cgi/content/abstract/102/25/9014}
}
@ARTICLE{Vishnivetskaya2011,
author = {Vishnivetskaya, Tatiana A. and Mosher, Jennifer J. and Palumbo, Anthony
V. and Yang, Zamin K. and Podar, Mircea and Brown, Steven D. and
Brooks, Scott C. and Gu, Baohua and Southworth, George R. and Drake,
Meghan M. and Brandt, Craig C. and Elias, Dwayne A.},
title = {Mercury and Other Heavy Metals Influence Bacterial Community Structure
in Contaminated Tennessee Streams},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {302-311},
number = {1},
abstract = {High concentrations of uranium, inorganic mercury [Hg(II)], and methylmercury
(MeHg) have been detected in streams located in the Department of
Energy reservation in Oak Ridge, TN. To determine the potential effects
of the surface water contamination on the microbial community composition,
surface stream sediments were collected 7 times during the year,
from 5 contaminated locations and 1 control stream. Fifty-nine samples
were analyzed for bacterial community composition and geochemistry.
Community characterization was based on GS 454 FLX pyrosequencing
with 235 Mb of 16S rRNA gene sequence targeting the V4 region. Sorting
and filtering of the raw reads resulted in 588,699 high-quality sequences
with lengths of >200 bp. The bacterial community consisted of 23
phyla, including Proteobacteria (ranging from 22.9 to 58.5% per sample),
Cyanobacteria (0.2 to 32.0%), Acidobacteria (1.6 to 30.6%), Verrucomicrobia
(3.4 to 31.0%), and unclassified bacteria. Redundancy analysis indicated
no significant differences in the bacterial community structure between
midchannel and near-bank samples. Significant correlations were found
between the bacterial community and seasonal as well as geochemical
factors. Furthermore, several community members within the Proteobacteria
group that includes sulfate-reducing bacteria and within the Verrucomicrobia
group appeared to be associated positively with Hg and MeHg. This
study is the first to indicate an influence of MeHg on the in situ
microbial community and suggests possible roles of these bacteria
in the Hg/MeHg cycle.},
doi = {10.1128/AEM.01715-10},
eprint = {http://aem.asm.org/cgi/reprint/77/1/302.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/1/302}
}
@ARTICLE{Visone2011,
author = {Visone, Rosa and Veronese, Angelo and Rassenti, Laura Z. and Balatti,
Veronica and Pearl, Dennis K. and Acunzo, Mario and Volinia, Stefano
and Taccioli, Cristian and Kipps, Thomas J. and Croce, Carlo M.},
title = {miR-181b is a biomarker of disease progression in chronic lymphocytic
leukemia},
journal = {Blood},
year = {2011},
volume = {118},
pages = {3072-3079},
number = {11},
abstract = {MicroRNAs play a crucial role in chronic lymphocytic leukemia. We
investigated whether microRNAs can discriminate patients with a progressive
disease from patients with a stable disease. We analyzed microRNA
expression on leukemic cells isolated from 358 sequential samples
of 114 patients with either stable or progressive disease. We found
that during the course of the disease the expression values of miR-181b,
the most dysregulated microRNA, decreased in samples of patients
with a progressive (P < .001, training and validation sets) but not
in samples of patients with a stable disease (P = .3, training set;
P = .2, validation set) over time. A drop of [≥] 50% between sequential
samples and/or a miR-181b value [≤] 0.005 at the starting time
point were significant to differentiate progressive from stable disease
(P = .004, training set; P < .001, validation set). These parameters
were associated with high risk of requiring treatment (risk ratio,
5.8; 95% confidence interval, 2.5-14.9). We also observed that miR-181b
targets Mcl-1 protein and that the decrease of its expression inversely
correlated with increased protein levels of MCL1 and BCL2 target
genes. We conclude that parameters defined on the basis of the miR-181b
expression values specify disease progression in chronic lymphocytic
leukemia and are associated with clinical outcome.},
doi = {10.1182/blood-2011-01-333484},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/11/3072.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/11/3072}
}
@ARTICLE{Vispe2009,
author = {Vispe, Stephane and DeVries, Luc and Creancier, Laurent and Besse,
Jerome and Breand, Sophie and Hobson, David J. and Svejstrup, Jesper
Q. and Annereau, Jean-Philippe and Cussac, Didier and Dumontet, Charles
and Guilbaud, Nicolas and Barret, Jean-Marc and Bailly, Christian},
title = {Triptolide is an inhibitor of RNA polymerase I and II-dependent transcription
leading predominantly to down-regulation of short-lived mRNA},
journal = {Mol. Cancer Ther.},
year = {2009},
volume = {8},
pages = {2780--2790},
number = {10},
month = oct,
abstract = {Triptolide, a natural product extracted from the Chinese plant Tripterygium
wilfordii, possesses antitumor properties. Despite numerous reports
showing the proapoptotic capacity and the inhibition of NF-{kappa}B-mediated
transcription by triptolide, the identity of its cellular target
is still unknown. To clarify its mechanism of action, we further
investigated the effect of triptolide on RNA synthesis in the human
non-small cell lung cancer cell line A549. Triptolide inhibited both
total RNA and mRNA de novo synthesis, with the primary action being
on the latter pool. We used 44K human pan-genomic DNA microarrays
and identified the genes primarily affected by a short treatment
with triptolide. Among the modulated genes, up to 98% are down-regulated,
encompassing a large array of oncogenes including transcription factors
and cell cycle regulators. We next observed that triptolide induced
a rapid depletion of RPB1, the RNA polymerase II main subunit that
is considered a hallmark of a transcription elongation blockage.
However, we also show that triptolide does not directly interact
with the RNA polymerase II complex nor does it damage DNA. We thus
conclude that triptolide is an original pharmacologic inhibitor of
RNA polymerase activity, affecting indirectly the transcription machinery,
leading to a rapid depletion of short-lived mRNA, including transcription
factors, cell cycle regulators such as CDC25A, and the oncogenes
MYC and Src. Overall, the data shed light on the effect of triptolide
on transcription, along with its novel potential applications in
cancers, including acute myeloid leukemia, which is in part driven
by the aforementioned oncogenic factors. [Mol Cancer Ther 2009;8(10):2780-90]},
url = {http://mct.aacrjournals.org/cgi/content/abstract/8/10/2780}
}
@ARTICLE{Visser2009,
author = {Visser, W. Edward and Heemstra, Karen A. and Swagemakers, Sigrid
M. A. and Ozgur, Zeliha and Corssmit, Eleonora P. and Burggraaf,
Jacobus and van Ijcken, Wilfred F. J. and van der Spek, Peter J.
and Smit, Johannes W. A. and Visser, Theo J.},
title = {Physiological Thyroid Hormone Levels Regulate Numerous Skeletal Muscle
Transcripts},
journal = {J. Clin. Endocrinol. Metab.},
year = {2009},
volume = {94},
pages = {3487--3496},
number = {9},
month = sep,
abstract = {Context: Skeletal muscle is an important target tissue for thyroid
hormone (TH). It is currently unknown which genes are regulated by
physiological TH levels. Objective: We examined the effects of L-thyroxine
on human skeletal muscle transcriptome. Design: Microarray analysis
of transcript levels was performed using skeletal muscle biopsies
from patients under euthyroid and hypothyroid conditions. Setting:
The study was conducted in a university hospital laboratory. Patients:
We studied skeletal muscle obtained from 10 thyroidectomized patients
with differentiated thyroid carcinoma on and after 4 wk off L-thyroxine
replacement. Mean Outcome Measures: Gene expression changes were
measured using microarrays. Results were analyzed using dedicated
statistical methods. Results: We detected 607 differentially expressed
genes on L-thyroxine treatment, of which approximately 60% were positively
and approximately 40% were negatively regulated. Representative genes
were validated by quantitative PCR. Genes involved in energy and
fuel metabolism were overrepresented among the up-regulated genes,
of which a large number were newly associated with thyroid state.
L-thyroxine therapy induced a large down-regulation of the primary
transcripts of the noncoding microRNA pair miR-206/miR-133b. Conclusion:
We demonstrated that physiological levels of TH regulate a myriad
of genes in human skeletal muscle. The identification of novel putatively
TH-responsive genes may provide the molecular basis of clinical effects
in subjects with different TH status. The observation that TH regulates
microRNAs reveals a new layer of complexity by which TH influences
cellular processes.},
url = {http://jcem.endojournals.org/cgi/content/abstract/94/9/3487}
}
@ARTICLE{Vital2010,
author = {Vital, Ana Luisa and Tabernero, Maria Dolores and Castrillo, Abel
and Rebelo, Olinda and Tao, Herminio and Gomes, Fernando and Nieto,
Ana Belen and Resende Oliveira, Catarina and Lopes, Maria Celeste
and Orfao, Alberto},
title = {Gene expression profiles of human glioblastomas are associated with
both tumor cytogenetics and histopathology},
journal = {Neuro Oncology},
year = {2010},
volume = {12},
pages = {991--1003},
number = {9},
month = sep,
abstract = {Despite the increasing knowledge about the genetic alterations and
molecular pathways involved in gliomas, few studies have investigated
the association between the gene expression profiles (GEP) and both
cytogenetics and histopathology of gliomas. Here, we analyzed the
GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas,
and 2 mixed tumors) and their association with tumor cytogenetics
and histopathology. Unsupervised and supervised analyses showed significantly
different GEP in low- vs high-grade gliomas, the most discriminating
genes including genes involved in the regulation of cell proliferation,
apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma
multiforme (GBM), 3 subgroups of tumors were identified according
to their GEP, which were closely associated with the cytogenetic
profile of their ancestral tumor cell clones: (i) EGFR amplification,
(ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary,
our results show a clear association between the GEP of gliomas and
tumor histopathology; additionally, among grade IV astrocytoma, GEP
are significantly associated with the cytogenetic profile of the
ancestral tumor cell clone. Further studies in larger series of patients
are necessary to confirm our observations.},
url = {http://neuro-oncology.oxfordjournals.org/cgi/content/abstract/12/9/991}
}
@ARTICLE{Vivancos2010,
author = {Vivancos, Ana P. and Guell, Marc and Dohm, Juliane C. and Serrano,
Luis and Himmelbauer, Heinz},
title = {Strand-specific deep sequencing of the transcriptome},
journal = {Genome Res.},
year = {2010},
volume = {20},
pages = {989--999},
number = {7},
month = jul,
abstract = {Several studies support that antisense-mediated regulation may affect
a large proportion of genes. Using the Illumina next-generation sequencing
platform, we developed DSSS (direct strand specific sequencing),
a strand-specific protocol for transcriptome sequencing. We tested
DSSS with RNA from two samples, prokaryotic (Mycoplasma pneumoniae)
as well as eukaryotic (Mus musculus), and obtained data containing
strand-specific information, using single-read and paired-end sequencing.
We validated our results by comparison with a strand-specific tiling
array data set for strain M129 of the simple prokaryote M. pneumoniae,
and by quantitative PCR (qPCR). The results of DSSS were very well
supported by the results from tiling arrays and qPCR. Moreover, DSSS
provided higher dynamic range and single-base resolution, thus enabling
efficient antisense detection and the precise mapping of transcription
start sites and untranslated regions. DSSS data for mouse confirmed
strand specificity of the protocol and the general applicability
of the approach to studying eukaryotic transcription. We propose
DSSS as a simple and efficient strategy for strand-specific transcriptome
sequencing and as a tool for genome annotation exploiting the increased
read lengths that next-generation sequencing technology now is capable
to deliver.},
url = {http://genome.cshlp.org/cgi/content/abstract/20/7/989}
}
@ARTICLE{Vizzardelli2006,
author = {Vizzardelli, Caterina and Pavelka, Norman and Luchini, Alessandra
and Zanoni, Ivan and Bendickson, Lee and Pelizzola, Mattia and Beretta,
Ottavio and Foti, Maria and Granucci, Francesca and Nilsen-Hamilton,
Marit and Ricciardi-Castagnoli, Paola},
title = {Effects of dexamethazone on LPS-induced activationand migration of
mouse dendritic cells revealed by a genome-wide transcriptional analysis},
journal = {Eur. J. Immunol.},
year = {2006},
volume = {36},
pages = {1504--1515},
number = {6},
abstract = {Abstract 10.1002/eji.200535488.abs While lipopolysaccharides (LPS)
induce dendritic cell (DC) maturation and migration to lymph nodes,
glucocorticoids such as dexamethazone (Dex) have a profound suppressive
effect on immune response. The mechanisms that might control this
suppressive effect of Dex have been extensively investigated in lymphocytes
as possible targets. Much less is known on the effects of Dex on
DC, although they are recognized to regulate immunity. To get insights
into possible combined effects of Dex and LPS on DC functions, we
have undertaken a genome-wide analysis of differentially expressed
genes of DC treated with Dex alone, LPS alone, or both, using high-density
oligonucleotide microarrays. Hierarchical clustering and principal
component analysis (PCA) agreed in identifying 24 h as the time
point that best discriminated the three treatments. Among the counteracting
effects we have observed an inhibition of Dex on the LPS-induced
up-regulation of the chemokine receptor CCR7. In vivo, Dex treatment
blocked the LPS-induced migration of DC, which lost their ability
to reach the draining lymph nodes. In addition, we observed a synergistic
effect of Dex and LPS on the expression of the secreted lipocalin 24p3,
which has been reported to induce apoptosis in T cells and thus
may be related to immune suppression.},
issn = {1521-4141},
keywords = {24p3, CCR7, Dendritic cell, Dexamethazone, Lipopolysaccharides},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200535488}
}
@ARTICLE{Vlad2011,
author = {Vlad, George and King, Jessica and Chang, Chih-Chao and Liu, Zhuoru
and Friedman, Richard A. and Torkamani, Ali A. and Suciu-Foca, Nicole},
title = {Gene profile analysis of CD8+ ILT3-Fc induced T suppressor cells},
journal = {Human Immunology},
year = {2011},
volume = {72},
pages = {107--114},
number = {2},
month = feb,
abstract = {Gene profile analysis of ILT3-Fc-induced Ts revealed a significant
upregulation of Zink finger proteins, most of which act as transcriptional
repressors. Included among these repressors is BCL6, which was shown
to play a critical role in the differentiation of ILT3-Fc-induced
T suppressor (Ts) cells. Genes implicated in cell cycle progression
were downregulated. Genes encoding numerous inflammatory cytokines
and chemokines were also downregulated. In contrast, antiapoptotic
genes, as well as members of the WNT and transforming growth factor-[beta]
pathways, were upregulated. This study elucidates certain important
aspects of Ts differentiation and function.},
issn = {0198-8859},
keywords = {CD8 T suppressor cells, Gene chip transcriptional profiling, WNT pathway},
url = {http://www.sciencedirect.com/science/article/pii/S0198885910005264}
}
@ARTICLE{Vlad2009,
author = {Vlad, George and Stokes, Michael B. and Liu, Zhuoru and Chang, Chih-Chao
and Sondermeijer, Hugo and Vasilescu, Elena R. and Colovai, Adriana
I. and Berloco, Pasquale and D'Agati, Vivette D. and Ratner, Lloyd
and Cortesini, Raffaello and Suciu-Foca, Nicole},
title = {Suppression of xenogeneic graft-versus-host disease by treatment
with immunoglobulin-like transcript 3-Fc},
journal = {Human Immunology},
year = {2009},
volume = {70},
pages = {663--669},
number = {9},
month = sep,
abstract = {Allogeneic hematopoietic cell transplantation represents an important
therapy for certain malignant and nonmalignant diseases. However,
graft-versus-host disease (GVHD) is a major cause of mortality and
morbidity. The search for agents that can efficiently suppress GVHD
has been going on for more than half a century. GVHD is particularly
strong in xenogeneic donor-recipient combinations, given the unlimited
number of potentially immunogenic antigens donor lymphocytes encounter
in the host. Using a hu-nonobese diabetic/severe combined immunodeficiency
(hu-NOD/SCID) [gamma]-null model of xenogeneic GVHD, we have demonstrated
that treatment with recombinant immunoglobulin-like transcript 3-Fc
protein induces the differentiation of CD8+ T suppressor cells and
blocks the cellular and humoral arm of the GVH reaction.},
issn = {0198-8859},
keywords = {GVHD, ILT3, CD8 T suppressor cells},
url = {http://www.sciencedirect.com/science/article/B6T3B-4WGK4C6-1/2/ab981aeab7742e4481995e86f114a423}
}
@ARTICLE{Vlaicu2010,
author = {Vlaicu, Sonia I. and Tegla, Cosmin A. and Cudrici, Cornelia D. and
Fosbrink, Matthew and Nguyen, Vingh and Azimzadeh, Philippe and Rus,
Violeta and Chen, Hegang and Mircea, Petru A. and Shamsuddin, Abulkalam
and Rus, Horea},
title = {Epigenetic modifications induced by RGC-32 in colon cancer},
journal = {Experimental and Molecular Pathology},
year = {2010},
volume = {88},
pages = {67--76},
number = {1},
month = feb,
abstract = {First described as a cell cycle activator, RGC-32 is both an activator
and a substrate for CDC2. Deregulation of RGC-32 expression has been
detected in a wide variety of human cancers. We have now shown that
RGC-32 is expressed in precancerous states, and its expression is
significantly higher in adenomas than in normal colon tissue. The
expression of RGC-32 was higher in advanced stages of colon cancer
than in precancerous states or the initial stages of colon cancer.
In order to identify the genes that are regulated by RGC-32, we used
gene array analysis to investigate the effect of RGC-32 knockdown
on gene expression in the SW480 colon cancer cell line. Of the 230
genes that were differentially regulated after RGC-32 knockdown,
a group of genes involved in chromatin assembly were the most significantly
regulated in these cells: RGC-32 knockdown induced an increase in
acetylation of histones H2B lysine 5 (H2BK5), H2BK15, H3K9, H3K18,
and H4K8. RGC-32 silencing was also associated with decreased expression
of SIRT1 and decreased trimethylation of histone H3K27 (H3K27me3).
In addition, RGC-32 knockdown caused a significantly higher percentage
of SW480 cells to enter S phase and subsequently G2/M. These data
suggest that RGC-32 may contribute to the development of colon cancer
by regulating chromatin assembly.},
issn = {0014-4800},
keywords = {RGC-32, Colon cancer, Gene array, Histone, Acetylation, Methylation},
url = {http://www.sciencedirect.com/science/article/B6WFB-4XKBYTX-1/2/e3b45d9de5e3856804258f5f0c36e47a}
}
@ARTICLE{Vlaming2007,
author = {de Vlaming, V. and Biales, A. and Riordan, D. and Markiewicz, D.
and Holmes, R. and Otis, P. and Zander, R. and Lazorchak, J.},
title = {Screening California surface waters for estrogenic endocrine disrupting
chemicals (EEDC) with a juvenile rainbow trout liver vitellogenin
mRNA procedure},
journal = {Science of The Total Environment},
year = {2007},
volume = {385},
pages = {66--79},
number = {1-3},
month = oct,
abstract = {Concern regarding the occurrence of chemicals that disrupt endocrine
system functions in aquatic species has heightened over the last
15 years. However, little attention has been given to monitoring
for estrogenic endocrine disrupting chemicals (EEDCs) in California's
freshwater ecosystems. The objective was to screen surface water
samples for estrogenic activity using vitellogenin (Vtg) mRNA quantification
in livers of juvenile rainbow trout by real-time reverse transcriptase
polymerase chain reaction (Q-RT PCR). Vtg mRNA analysis of livers
from fish exposed to 113 ambient water samples collected from surface
waters in California's Central Valley and northern area indicated
that six samples (5% of total) may have contained EEDCs. The six
samples induced marginal, but statistically significant, increases
of Vtg mRNA. No ambient water sample evoked Vtg mRNA responses equivalent
to those in positive controls (all responses were less than 2% of
the positive control response). Thus, EEDC concentrations in these
samples were low (at or near the threshold for the procedure) or
results may have included false positives. To establish a more definitive
assessment of EEDC occurrence, follow-up screening at sites where
statistically significant, but weak, estrogenic activity was observed
is recommended. Overall, results reveal that a majority of the California
surface waters tested were below EEDC detection threshold concentration
for the screening procedure utilized.},
issn = {0048-9697},
keywords = {Estrogenic endocrine disruption, Vitellogenin mRNA, Rainbow trout,
California surface waters},
url = {http://www.sciencedirect.com/science/article/B6V78-4P6TGYX-3/2/69a49839f455b75cab057d80c44089b7}
}
@ARTICLE{Vo2010,
author = {Vo, Thi Kim Duy and Godard, Patrice and de Saint-Hubert, Marie and
Morrhaye, Gabriel and Bauwens, Emilie and Debacq-Chainiaux, Florence
and Glupczynski, Youri and Swine, Christian and Geenen, Vincent and
Martens, Henri J. and Toussaint, Olivier},
title = {Transcriptomic biomarkers of human ageing in peripheral blood mononuclear
cell total RNA},
journal = {Experimental Gerontology},
year = {2010},
volume = {45},
pages = {188--194},
number = {3},
month = mar,
abstract = {Age-related changes of gene expression contribute to the physiological
alteration observed with human ageing. Herein, the abundance of a
selection of 148 transcripts involved in immunosenescence and stress
response was compared in total RNA of PBMC of healthy young to middle-age
probands (35.0 ± 6.5 year old) and healthy old probands (82.5 ± 6.8 year
old). This study provides a list of 16 differentially abundant transcripts
species in the healthy old probands. Thus, these changes of abundance
can be considered as easily accessible biomarkers of ageing. Some
of these differential abundances like CD28, CD69, LCK (decreased
abundance in old subjects), CD86, Cathepsin D, H and S (increased
abundance in old subjects) might explain biochemical and cytochemical
changes observed at the protein level in the immune system and thus
might correspond to regulatory processes affecting the ageing process.
Indeed these changes reflect the low-grade pro-inflammatory status
observed in old persons and suggest a hypo-responsiveness of T-cells
together with an increase in antigen presentation potential. In addition,
among the differentially abundant transcripts were transcripts involved
in the oxidative stress response HMOX1 and HSPA6 mRNAs were found
as more abundant in PBMC from elderly subjects.},
issn = {0531-5565},
keywords = {Ageing, PBMC, Gene expression, Biomarker, Immunosenescence, Oxidative
stress, cDNA array},
url = {http://www.sciencedirect.com/science/article/B6T6J-4XW00B8-1/2/8dd36c78c2fb672a5026318391b41832}
}
@ARTICLE{Vo2011a,
author = {Vo, Thi Kim Duy and Godard, Patrice and de Saint-Hubert, Marie and
Morrhaye, Gabriel and Debacq-Chainiaux, Florence and Swine, Christian
and Geenen, Vincent and Martens, Henri J. and Toussaint, Olivier},
title = {Differentially abundant transcripts in PBMC of hospitalized geriatric
patients with hip fracture compared to healthy aged controls},
journal = {Experimental Gerontology},
year = {2011},
volume = {46},
pages = {257--264},
number = {4},
month = apr,
abstract = {The abundance of a selection of transcript species involved in inflammation,
immunosenescence and stress response was compared between PBMC of
35 geriatric patients with hip fracture in acute phase (days 2-4
after hospitalization) or convalescence phase (days 7-10) and 28
healthy aged controls. Twenty-nine differentially abundant transcripts
were identified in acute phase versus healthy ageing. Twelve of these
transcripts remained differentially abundant in convalescence phase,
and 22 were similarly differentially abundant in acute phase of geriatric
infectious diseases. Seven of these 22 transcripts were previously
identified as differentially abundant in PBMC of healthy aged versus
healthy young controls, with further alteration for CD28, CD69, LCK,
CTSD, HMOX1, and TNFRSF1A in acute phase after geriatric hip fracture
and infectious diseases. The next question is whether these alterations
are common to other geriatric diseases and/or preexist before the
clinical onset of the diseases.},
issn = {0531-5565},
keywords = {Ageing, Hip fracture, PBMC, Gene expression, Inflammation, Immunosenescence,
Oxidative stress},
url = {http://www.sciencedirect.com/science/article/pii/S0531556510003888}
}
@ARTICLE{Vo2011,
author = {Vo, Thi Kim Duy and de Saint-Hubert, Marie and Morrhaye, Gabriel
and Godard, Patrice and Geenen, Vincent and Martens, Henri J. and
Debacq-Chainiaux, Florence and Swine, Christian and Toussaint, Olivier},
title = {Transcriptomic biomarkers of the response of hospitalized geriatric
patients admitted with heart failure. Comparison to hospitalized
geriatric patients with infectious diseases or hip fracture},
journal = {Mechanisms of Ageing and Development},
year = {2011},
volume = {132},
pages = {131--139},
number = {3},
month = mar,
abstract = {The abundance of a preselection of transcripts involved in inflammation,
immunosenescence and stress response was compared between PBMC of
healthy aged donors and aged patients in acute phase of heart failure
and at recovery. This study identified 22 transcripts differentially
abundant in acute phase of heart failure versus healthy aged subjects.
Transcripts involved in inflammation and oxidative stress were more
abundant. Those associated with T-cell functions were less abundant.
The results were compared to two other major acute geriatric issues:
infectious diseases and hip fracture. In acute phase, compared to
healthy aged subjects, the abundance of 15/22 transcripts was also
altered in both geriatric infectious diseases and hip fracture. Many
variations had not vanished at the recovery phase. The abundance
of CD28, CD69, LCK, HMOX1, TNFRSF1A transcripts, known to be altered
in healthy aged versus healthy young subjects, was further affected
in acute phase of the three geriatric diseases considered. The transcript
levels of BCL2, CASP8, CCL5, DDIT3, EGR3, IL10RB, IL1R2, SERPINB2
and TIMP1 were affected in all three pathological conditions compared
to healthy aged, but not versus healthy young subjects. In conclusion,
this work provides critical targets for therapeutic research on geriatric
heart failure, infectious diseases and hip fracture.},
issn = {0047-6374},
keywords = {Ageing, Gene expression, Heart failure, Inflammation, Immunosenescence,
Oxidative stress},
url = {http://www.sciencedirect.com/science/article/pii/S0047637411000248}
}
@ARTICLE{Vock2008,
author = {Vock, Christina and Gleissner, Mareike and Klapper, Maja and Döring,
Frank},
title = {Oleate regulates genes controlled by signaling pathways of mitogen-activated
protein kinase, insulin, and hypoxia},
journal = {Nutrition Research},
year = {2008},
volume = {28},
pages = {681--689},
number = {10},
month = oct,
abstract = {Oleate (C18:1) is, besides palmitate (C16:0), the most abundant fatty
acid in the human diet, and its involvement in the development of
insulin resistance is broadly discussed. Because its influence on
gene expression is poorly defined in mammalian cells, we performed
whole genome expression profiling and quantitative real-time polymerase
chain reaction in the human hepatocyte cell line HepG2 to identify
oleate-regulated genes. In this respect, HepG2 cells were exposed
for 24 hours to a physiologic concentration of oleate coupled to
bovine serum albumin (BSA) (200 [mu]mol/L) or BSA alone. Subsequent
microarray analysis revealed 14 genes that were significantly (single-sided
permutational t test, P < .05) regulated after oleate treatment.
To decipher the functional and regulatory connections of these genes,
a text mining approach combined with transcription factor binding
site analysis was performed using Genomatix BiblioSphere (Munich,
Germany) and MatInspector (Munich, Germany). The oleate-inducible
genes encoding early growth response 1, c-fos, S-phase kinase-associated
protein 2, and splicing factor 2 are mapped into a network, which
is controlled by signaling pathways of mitogen-activated protein
kinase, insulin, or hypoxia. Comparative in silico promoter analysis
revealed putative regulation of oleate-sensitive genes through v-ets
erythroblastosis virus E26 oncogene homolog 1 and retinoid X receptor
family. In sum, a physiologic oleate concentration modulates genes
expression in a very sensitive way as 14 genes were regulated.},
issn = {0271-5317},
keywords = {Gene expression, Hepatocytes, HepG2 cell culture, Microarray analysis,
Oleic acid, Transcription factors, BSA, bovine serum albumin, EGR1,
early growth response 1, ETS1, E26 v-ets erythroblastosis virus oncogene
homolog 1 family, ETSF, ETS1 factor, FCS, foetal calf serum, FOS,
v-fos FBJ murine osteosarcoma viral oncogene homolog, HBSS, Hanks
balanced salt solution, MAP, mitogen-activated protein, PNPLA2, patatin-like
phospholipase domain containing 2, qRT-PCR, quantitative real-time
polymerase chain reaction, RPMI, Roswell Park Memorial Institute,
RXR, retinoid X receptor, SFRS1, splicing factor, arginine/serine-rich
1 (splicing factor 2), SKP2, S-phase kinase-associated protein 2
(p45), TF, transcription factor},
url = {http://www.sciencedirect.com/science/article/B6TB1-4TRKDXC-6/2/905a0cb51abf01f21f285a149cd21bed}
}
@ARTICLE{Vock2007,
author = {Vock, Christina and Gleissner, Mareike and Klapper, Maja and Döring,
Frank},
title = {Identification of palmitate-regulated genes in HepG2 cells by applying
microarray analysis},
journal = {Biochimica et Biophysica Acta (BBA) - General Subjects},
year = {2007},
volume = {1770},
pages = {1283--1288},
number = {9},
month = sep,
abstract = {Palmitate is the most abundant saturated fatty acid in the human diet
and the major one synthesized de novo. To identify palmitate-regulated
genes we performed whole genome mRNA expression profiling by using
human hepatoma HepG2 cells. We identified eleven genes which are
significantly (single-sided permutational t-test, p < 0.05) regulated
by low concentration of palmitate (50 [mu]M). We observed a decreased
expression of five metallothioneins, and an increased expression
of liver expressed plasminogen activator inhibitor-1 protein and
insulin-like growth factor II, which play a prominent role in the
development of the metabolic syndrome. Comparative promoter analysis
in-silico revealed common transcriptional regulation of differentially
expressed genes through erythroid kruppel-like factor and members
of the zinc binding protein factor family. In conclusion, low physiological
palmitate concentrations changed expression of very responsive genes.},
issn = {0304-4165},
keywords = {Gene expression, Hepatocytes, Microarray, Palmitate, Transcription
factor},
url = {http://www.sciencedirect.com/science/article/B6T1W-4P59X61-1/2/1759aecb5f4af662a6dc1f6af0a13879}
}
@ARTICLE{VOELCKEL2008,
author = {VOELCKEL, C. and HEENAN, P. B. and JANSSEN, B. and REICHELT, M. and
FORD, K. and HOFMANN, R. and LOCKHART, P. J.},
title = {Transcriptional and biochemical signatures of divergence in natural
populations of two species of New Zealand alpine Pachycladon},
journal = {Molecular Ecology},
year = {2008},
volume = {17},
pages = {4740--4753},
number = {21},
abstract = {Abstract New Zealand is diverse in alpine and subalpine environments,
a consequence of Late Tertiary tectonic and climatic change. However,
few studies have sought to evaluate the importance of these environments
as abiotic drivers in the diversification of plant species. Of particular
interest is the Late Tertiary radiation of Pachycladon, an endemic
New Zealand genus of alpine cress. Here we report observations on
genome-wide levels of differential expression measured in the habitats
of two closely related species of Pachycladon with distinct altitudinal
preferences. Using Arabidopsis microarrays, we have identified 310
predominantly hormone- and stress-response genes up-regulated in
Pachycladon fastigiata and 324 genes up-regulated in Pachycladon
enysii. Expression patterns for glucosinolate biosynthesis and hydrolysis
genes (MAM1, MAM-I, MAM-D, AOP2, ESP, ESM1) as well as flavonoid
biosynthesis genes (F3’H, FLS, FAH1) were found to be species specific.
Predicted differences in flavonoid contents were partly confirmed
by high performance liquid chromatography analysis. Differences in
glucosinolate profiles and glucosinolate hydrolysis products obtained
by high performance liquid chromatography and gas chromatography–mass
spectrometry analysis, respectively, also supported inferences from
expression analyses. Five glucosinolate chemotypes were matched to
known Arabidopsis ecotypes, and the potential adaptive significance
of these chemotypes has been discussed. Our findings, in contrast
to expectations for evolution of the New Zealand flora, suggest that
biotic drivers, such as plant–herbivore interactions, are likely
to be as important as abiotic drivers in the diversification of Pachycladon.},
issn = {1365-294X},
keywords = {adaptive radiation, cross-species hybridization, expression profiling,
glucosinolates, Pachycladon, quercetin},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2008.03933.x}
}
@ARTICLE{Voelkerding2010,
author = {Voelkerding, Karl V. and Dames, Shale and Durtschi, Jacob D.},
title = {Next Generation Sequencing for Clinical Diagnostics-Principles and
Application to Targeted Resequencing for Hypertrophic Cardiomyopathy:
A Paper from the 2009 William Beaumont Hospital Symposium on Molecular
Pathology},
journal = {J. Mol. Diagn.},
year = {2010},
volume = {12},
pages = {539--551},
number = {5},
month = sep,
abstract = {During the past five years, new high-throughput DNA sequencing technologies
have emerged; these technologies are collectively referred to as
next generation sequencing (NGS). By virtue of sequencing clonally
amplified DNA templates or single DNA molecules in a massively parallel
fashion in a flow cell, NGS provides both qualitative and quantitative
sequence data. This combination of information has made NGS the technology
of choice for complex genetic analyses that were previously either
technically infeasible or cost prohibitive. As a result, NGS has
had a fundamental and broad impact on many facets of biomedical research.
In contrast, the dissemination of NGS into the clinical diagnostic
realm is in its early stages. Though NGS is powerful and can be envisioned
to have multiple applications in clinical diagnostics, the technology
is currently complex. Successful adoption of NGS into the clinical
laboratory will require expertise in both molecular biology techniques
and bioinformatics. The current report presents principles that underlie
NGS including sequencing library preparation, sequencing chemistries,
and an introduction to NGS data analysis. These concepts are subsequently
further illustrated by showing representative results from a case
study using NGS for targeted resequencing of genes implicated in
hypertrophic cardiomyopathy.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/12/5/539}
}
@ARTICLE{Voets2011,
author = {A.M. Voets and M. Huigsloot and P.J. Lindsey and A.M. Leenders and
W.J.H. Koopman and P.H.G.M. Willems and R.J. Rodenburg and J.A.M.
Smeitink and H.J.M. Smeets},
title = {Transcriptional changes in OXPHOS complex I deficiency are related
to anti-oxidant pathways and could explain the disturbed calcium
homeostasis},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
year = {2011},
pages = { - },
number = {0},
abstract = {Defective complex I (CI) is the most common type of oxidative phosphorylation
disease, with an incidence of 1 in 5000 live births. Here, whole
genome expression profiling of fibroblasts from CI deficient patients
was performed to gain insight into the cell pathological mechanism.
Our results suggest that patient fibroblasts responded to oxidative
stress by Nrf2-mediated induction of the glutathione antioxidant
system and Gadd45-mediated activation of the DNA damage response
pathway. Furthermore, the observed reduced expression of selenoproteins,
might explain the disturbed calcium homeostasis previously described
for the patient fibroblasts and might be linked to endoplasmic reticulum
stress. These results suggest that both glutathione and selenium
metabolism are potentially therapeutic targets in CI deficiency.},
doi = {10.1016/j.bbadis.2011.10.009},
issn = {0925-4439},
keywords = {Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0925443911002328}
}
@ARTICLE{Vogel2010,
author = {Vogel, Heiko and Heidel, Andrew and Heckel, David and Groot, Astrid},
title = {Transcriptome analysis of the sex pheromone gland of the noctuid
moth Heliothis virescens },
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {29},
number = {1},
abstract = {BACKGROUND:The chemical components of sex pheromones have been determined
for more than a thousand moth species, but so far only a handful
of genes encoding enzymes responsible for the biosynthesis of these
compounds have been identified. For understanding the evolution of
moth sexual communication, it is essential to know which genes are
involved in the production of specific pheromone components and what
controls the variation in their relative frequencies in the pheromone
blend. We used a transcriptomic approach to characterize the pheromone
gland of the Noctuid moth Heliothis virescens, an important agricultural
pest, in order to obtain substantial general sequence information
and to identify a range of candidate genes involved in the pheromone
biosynthetic pathway.RESULTS:To facilitate identifying sets of genes
involved in a broad range of processes and to capture rare transcripts,
we developed our majority of ESTs from a normalized cDNA library
of Heliothis virescens pheromone glands (PG). Combining these with
a non-normalized library yielded a total of 17,233 ESTs, which assembled
into 2,082 contigs and 6,228 singletons. Using BLAST searches of
the NR and Swissprot databases we were able to identify a large number
of putative unique gene elements (unigenes), which we compared to
those derived from previous transcriptomic surveys of the larval
stage of Heliothis virescens. The distribution of unigenes among
GO Biological Process functional groups shows an overall similarity
between PG and larval transcriptomes, but with distinct enrichment
of specific pathways in the PG. In addition, we identified a large
number of candidate genes in the pheromone biosynthetic pathways.CONCLUSION:These
data constitute one of the first large-scale EST-projects for Noctuidae,
a much-needed resource for exploring these pest species. Our analysis
shows a surprisingly complex transcriptome and we identified a large
number of potential pheromone biosynthetic pathway and immune-related
genes that can be applied to population and systematic studies of
Heliothis virescens and other Noctuidae.},
doi = {10.1186/1471-2164-11-29},
issn = {1471-2164},
pubmedid = {20074338},
url = {http://www.biomedcentral.com/1471-2164/11/29}
}
@ARTICLE{Vogel2007,
author = {Vogel, Jason R. and Stoeckel, Donald M. and Lamendella, Regina and
Zelt, Ronald B. and Santo Domingo, Jorge W. and Walker, Steven R.
and Oerther, Daniel B.},
title = {Identifying Fecal Sources in a Selected Catchment Reach Using Multiple
Source-Tracking Tools},
journal = {J. Environ. Qual.},
year = {2007},
volume = {36},
pages = {718--729},
number = {3},
month = apr,
abstract = {Given known limitations of current microbial source-tracking (MST)
tools, emphasis on small, simple study areas may enhance interpretations
of fecal contamination sources in streams. In this study, three MST
tools--Escherichia coli repetitive element polymerase chain reaction
(rep-PCR), coliphage typing, and Bacteroidales 16S rDNA host-associated
markers--were evaluated in a selected reach of Plum Creek in south-central
Nebraska. Water-quality samples were collected from six sites. One
reach was selected for MST evaluation based on observed patterns
of E. coli contamination. Despite high E. coli concentrations, coliphages
were detected only once among water samples, precluding their use
as a MST tool in this setting. Rep-PCR classification of E. coli
isolates from both water and sediment samples supported the hypothesis
that cattle and wildlife were dominant sources of fecal contamination,
with minor contributions by horses and humans. Conversely, neither
ruminant nor human sources were detected by Bacteroidales markers
in most water samples. In bed sediment, ruminant- and human-associated
Bacteroidales markers were detected throughout the interval from
0 to 0.3 m, with detections independent of E. coli concentrations
in the sediment. Although results by E. coli-based and Bacteroidales-based
MST methods led to similar interpretations, detection of Bacteroidales
markers in sediment more commonly than in water indicates that different
tools to track fecal contamination (in this case, tools based on
Bacteroidales DNA and E. coli isolates) may have varying relevance
to the more specific goal of tracking the sources of E. coli in watersheds.
This is the first report of simultaneous, toolbox approach application
of a library-based and marker-based MST analyses to flowing surface
water.},
url = {http://jeq.scijournals.org/cgi/content/abstract/36/3/718}
}
@ARTICLE{Vogel-vandenBosch2008,
author = {de Vogel-van den Bosch, Heleen M. and de Wit, Nicole J. W. and Hooiveld,
Guido J. E. J. and Vermeulen, Hanneke and van der Veen, Jelske N.
and Houten, Sander M. and Kuipers, Folkert and Muller, Michael and
van der Meer, Roelof},
title = {A cholesterol-free, high-fat diet suppresses gene expression of cholesterol
transporters in murine small intestine},
journal = {Am J Physiol Gastrointest Liver Physiol},
year = {2008},
volume = {294},
pages = {G1171--1180},
number = {5},
month = may,
abstract = {Transporters present in the epithelium of the small intestine determine
the efficiency by which dietary and biliary cholesterol are taken
up into the body and thus control whole-body cholesterol balance.
Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into
the enterocyte, whereas ATP-binding cassette transporters Abca1 and
Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from
the enterocyte toward plasma HDL and back into the intestinal lumen,
respectively. Abca1, Abcg5, and Abcg8 are well-established liver
X receptor (LXR) target genes. We examined the effects of a high-fat
diet on expression and function of cholesterol transporters in the
small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all
downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat
diet. The high-fat diet did not affect biliary cholesterol secretion
but diminished fractional cholesterol absorption from 61 to 42% (P
< 0.05). In an acute experiment in which triacylglycerols of unsaturated
fatty acids were given by gavage, we found that this downregulation
occurs within a 6-h time frame. Studies in LXR{alpha}-null mice,
confirmed by in vitro data, showed that fatty acid-induced downregulation
of cholesterol transporters is LXR{alpha} independent and associated
with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme
A reductase activity that reflects induction of cholesterol biosynthesis
as well as with a doubling of neutral fecal sterol loss. This study
highlights the induction of adaptive changes in small intestinal
cholesterol metabolism during exposure to dietary fat.},
url = {http://ajpgi.physiology.org/cgi/content/abstract/294/5/G1171}
}
@ARTICLE{Vogt2006,
author = {Vogt, Ina R. and Lees, Andrew J. and Evert, Bernd O. and Klockgether,
Thomas and Bonin, Michael and Wüllner, Ullrich},
title = {Transcriptional changes in multiple system atrophy and Parkinson's
disease putamen},
journal = {Experimental Neurology},
year = {2006},
volume = {199},
pages = {465--478},
number = {2},
month = jun,
abstract = {Multiple system atrophy (MSA) and sporadic, non-mendelian Parkinson's
disease (PD) are progressive neurodegenerative disorders with overlapping
clinical symptoms and pathology. The etiology of both disorders is
unknown, and complex combinations of multiple susceptibility genes
and environmental factors are thought to be involved. Both disorders
are characterized by ubiquitous [alpha]-synuclein aggregates in distinct
regions and cell types of the central nervous system. In PD, [alpha]-synuclein-positive
aggregates appear to be largely neuronal while in MSA oligodendroglial
inclusions prevail. In PD patients, the [alpha]-synuclein pathology
is thought to evolve in a rather regular pattern, starting in the
brainstem and olfactory bulb and extending gradually onto the substantia
nigra and ultimately the cerebral cortex while the cerebellum is
largely spared. MSA pathology has not been graded in a similar way
yet; neuropathological analyses revealed neurodegeneration and gliosis
primarily in the brainstem, midbrain and basal ganglia and the cerebellum,
while the cortex is largely spared. To identify disease-specific
transcriptional patterns in MSA, we chose CNS regions differentially
affected in MSA and PD for comparative gene expression profiling:
putamen, cerebellum and occipital cortex. Four genes were regulated
in both MSA and PD putamen and twelve in MSA and PD cerebellum. Regulated
transcripts were validated using real-time quantitative RT-PCR, and
immunohistochemistry was performed for the most significantly downregulated
transcripts in MSA and PD putamen, GPR86 and RGS14, associated with
G protein signaling and transcriptional regulation.},
issn = {0014-4886},
keywords = {Expression profiling, Postmortem brain tissue, cDNA oligonucleotide,
Microarrays, Multiple system atrophy, Parkinson's disease, Occipital
cortex, Putamen, G proteins},
url = {http://www.sciencedirect.com/science/article/B6WFG-4JS20GN-2/2/7253aa959b66b9e871d77a0f1428c2c1}
}
@ARTICLE{Voigt2007,
author = {Voigt, Birgit and Hoi, Le Thi and Jürgen, Britta and Albrecht, Dirk
and Ehrenreich, Armin and Veith, Birgit and Evers, Stefan and Maurer,
Karl-Heinz and Hecker, Michael and Schweder, Thomas},
title = {The glucose and nitrogen starvation response of Bacillus licheniformis},
journal = {Proteomics},
year = {2007},
volume = {7},
pages = {413--423},
number = {3},
abstract = {Abstract The glucose and nitrogen starvation stimulons of Bacillus
licheniformis were determined by transcriptome and proteome analyses.
Under both starvation conditions, the main response of B. licheniformis
was a switch to the usage of alternative nutrient sources. This was
indicated by an induction of genes involved in the metabolism of
C-2 substrates during glucose limitation. In addition, B. licheniformis
seems to be using other organic substances like amino acids and lipids
as carbon sources when subjected to glucose starvation. This observation
is supported by the induction of a high number of genes coding for
proteins involved in amino acid and lipid degradation. During nitrogen
starvation, genes for several proteases and peptidases involved in
nitrate and nitrite assimilation were induced, which enables this
bacterium to recruit nitrogen from alternative sources. Both starvation
conditions led to a down-regulation of transcription of most vegetative
genes, which was subsequently reflected by a reduced synthesis of
the corresponding proteins. A selected set of genes was induced by
both starvation conditions. Among them were yvyD, citA and the putative
methylcitrate shunt genes mmgD, mmgE and yqiQ. However, both starvation
conditions did not induce a general SigmaB-dependent stress response.},
issn = {1615-9861},
keywords = {Bacillus licheniformis, Glucose starvation, Nitrogen starvation, Transcriptome},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200600556}
}
@ARTICLE{Voineagu2011,
author = {Voineagu, Irina and Wang, Xinchen and Johnston, Patrick and Lowe,
Jennifer K. and Tian, Yuan and Horvath, Steve and Mill, Jonathan
and Cantor, Rita M. and Blencowe, Benjamin J. and Geschwind, Daniel
H.},
title = {Transcriptomic analysis of autistic brain reveals convergent molecular
pathology},
journal = {Nature},
year = {2011},
volume = {advance online publication},
pages = {--},
month = may,
comment = {10.1038/nature10110},
issn = {1476-4687},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nature10110}
}
@ARTICLE{Voisin2011,
author = {Voisin, Thierry and El Firar, Aadil and Fasseu, Magali and Rouyer-Fessard,
Christiane and Descatoire, Veronique and Walker, Francine and Paradis,
Valerie and Bedossa, Pierre and Henin, Dominique and Lehy, Therese
and Laburthe, Marc},
title = {Aberrant Expression of OX1 Receptors for Orexins in Colon Cancers
and Liver Metastases: an Openable Gate to Apoptosis},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {3341--3351},
number = {9},
month = may,
abstract = {Resistance to apoptosis is a recurrent theme in colon cancer. We have
shown previously that the 7-transmembrane spanning receptor OX1R
for orexins promotes robust apoptosis in the human colon cancer cell
line HT29 through an entirely novel mechanism involving phosphorylation
of tyrosine-based motifs in OX1R. Here, we investigated the status
of OX1R in a large series of human colorectal tumors and hepatic
metastases. All primary colorectal tumors regardless of their localization
and Duke's stages and all hepatic metastases tested expressed OX1R
mRNA and/or protein. In sharp contrast, adjacent normal colonocytes
or hepatocytes as well as control normal tissues were negative. Next,
we showed that nine human colon cancer cell lines established from
primary tumors or metastases expressed OX1R mRNA and underwent important
apoptosis on orexin-A challenge. Most interestingly, orexin-A also
promoted robust apoptosis in cells that are resistant to the most
commonly used drug in colon cancer chemotherapy, 5-fluorouracil.
When human colon cancer cells were xenografted in nude mice, orexin-A
administered at day 0 strongly slowed the tumor growth and even reversed
the development of established tumors when administered 7 days after
cell inoculation. Orexin-A also acts by promoting tumor apoptosis
in vivo because caspase-3 is activated in tumors on orexin treatment
of nude mice. These findings support that OX1R is an Achilles heel
of colon cancers, even after metastasis or chemoresistance. They
suggest that OX1R agonists might be novel candidates for colon cancer
therapy. Cancer Res; 71(9); 3341-51. (C)2011 AACR.},
comment = {10.1158/0008-5472.CAN-10-3473},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/9/3341}
}
@ARTICLE{Volate2009,
author = {Volate, Suresh R. and Muga, Stephanie J. and Issa, Ala Y. and Nitcheva,
Daniela and Smith, Theresa and Wargovich, Michael J.},
title = {Epigenetic modulation of the retinoid X receptor α by green tea
in the azoxymethane-ApcMin/+ mouse model of intestinal cancer},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {920--933},
number = {10},
abstract = {Abstract 10.1002/mc.20542.abs We investigated the possible mechanisms
of inhibition of colorectal carcinogenesis by green tea (GT) in azoxymethane-treated
(AOM) ApcMin/+ mice. Mice received water or a 0.6% (w/v) solution
of GT as the only source of beverage. GT treatment commenced at the
8th week of age and lasted for 8 wk. The treatment caused a statistically
significant reduction in the number of newly formed tumors (28%,
P < 0.05). Immunohistochemical analysis showed that GT decreased
the levels of β-catenin and its downstream target cyclin D1. To
probe a mechanism, we further investigated the expression of retinoic
X receptor alpha (RXRα) in AOM/ApcMin/+ tumors. Our results show
that RXRα is selectively downregulated in AOM/ApcMin/+ mouse intestinal
tumors. In contrast, other retinoic receptors including retinoic
acid receptor alpha (RARα), RARβ, RXRβ, and RXRγ were all expressed
in ApcMin/+ adenomas. Furthermore, our results show that RXRα downregulation
is an early event in colorectal carcinogenesis and is independent
of β-catenin expression. GT significantly increased the protein
levels of RXRα. In addition, RT-PCR analysis showed that GT induced
a similar increase in the levels of RXRα mRNA. Genomic bisulfite
treatment of colonic DNA followed by pyrosequencing of 24 CpG sites
in the promoter region of RXRα gene showed a significant decrease
in CpG methylation with GT treatment. The results suggest that a
low concentration of GT is sufficient to desilence RXRα and inhibit
intestinal tumorigenesis in the ApcMin/+ mouse. Mol. Carcinog. ©
2009 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {green tea, colon cancer, azoxymethane (AOM), ApcMin/+ mouse model,
β-catenin, cyclin D1, RXRα, methylation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20542}
}
@ARTICLE{Volk2010,
author = {Volk, David W. and Eggan, Stephen M. and Lewis, David A.},
title = {Alterations in Metabotropic Glutamate Receptor 1{alpha} and Regulator
of G Protein Signaling 4 in the Prefrontal Cortex in Schizophrenia},
journal = {Am J Psychiatry},
year = {2010},
volume = {167},
pages = {1489--1498},
number = {12},
month = dec,
abstract = {ObjectiveCertain cognitive deficits in individuals with schizophrenia
have been linked to disturbed gamma-aminobutyric acid (GABA) and
glutamate neurotrans-mission in the prefrontal cortex. Thus, it is
important to understand how the mechanisms that regulate GABA and
glutamate neurotransmission are altered in schizophrenia. For example,
group I metabo-tropic glutamate receptors (mGluR1{alpha}, mGluR5)
modulate both GABA and gluta-mate systems. In addition, regulator
of G protein signaling 4 (RGS4) reduces intra-cellular signaling
through several different G protein-coupled receptors, including
group I mGluRs. Finally, the endocannabinoid system plays an important
role in regulating GABA and glutamate neurotrans-mission. The status
of endocannabinoid ligands, such as 2-arachidonoylglycerol, can be
inferred in part through measures of diacylglycerol lipase and monoglyceride
lipase, which synthesize and degrade 2-arachidonoylglycerol, respectively.
MethodQuantitative polymerase chain reaction was used to measure
mRNA levels for group I mGluRs, RGS4, and markers of the endocannabinoid
system in the prefrontal cortex Brodmann's area 9 of 42 schizophrenia
subjects and matched normal comparison subjects. Similar analyses
in monkeys chronically exposed to haloperidol, olanzapine, or placebo
were also conducted. ResultsSchizophrenia subjects had higher mRNA
levels for mGluR1{alpha} and lower mRNA levels for RGS4, and these
differences did not appear to be attributable to antipsychotic medications
or other potential confounds. In contrast, no differences between
subject groups were found in mRNA levels for endocannabinoid synthesizing
and metabolizing enzymes. ConclusionsTogether, higher mGluR1{alpha}
and lower RGS4 mRNA levels may represent a disturbed "molecular hub"
in schizophrenia that may disrupt the function of prefrontal cortical
networks, including both GABA and glutamate systems.},
comment = {10.1176/appi.ajp.2010.10030318},
url = {http://ajp.psychiatryonline.org/cgi/content/abstract/167/12/1489}
}
@ARTICLE{Volk2011,
author = {Volk, David W. and Radchenkova, Polina V. and Walker, Erin M. and
Sengupta, Elizabeth J. and Lewis, David A.},
title = {Cortical Opioid Markers in Schizophrenia and across Postnatal Development},
journal = {Cereb Cortex},
year = {2011},
pages = {bhr202},
abstract = {Certain cognitive deficits in schizophrenia have been linked to dysfunction
of prefrontal cortical (PFC) {gamma}-aminobutyric acid (GABA) neurons
and appear neurodevelopmental in nature. Since opioids suppress GABA
neuron activity, we conducted the first study to determine 1) whether
the {micro} opioid receptor (MOR), {delta} opioid receptor (DOR),
and opioid ligand proenkephalin are altered in the PFC of a large
cohort of schizophrenia subjects and 2) the postnatal developmental
trajectory in monkey PFC of opioid markers that are altered in schizophrenia.
We used quantitative polymerase chain reaction to measure mRNA levels
from 42 schizophrenia and 42 matched healthy comparison subjects;
18 monkeys chronically exposed to haloperidol, olanzapine, or placebo;
and 49 monkeys aged 1 week-11.5 years. We found higher levels for
MOR mRNA (+27%) in schizophrenia but no differences in DOR or proenkephalin
mRNAs. Elevated MOR mRNA levels in schizophrenia did not appear to
be explained by substance abuse, psychotropic medications, or illness
chronicity. Finally, MOR mRNA levels declined through early postnatal
development, stabilized shortly before adolescence and increased
across adulthood in monkey PFC. In schizophrenia, higher MOR mRNA
levels may contribute to suppressed PFC GABA neuron activity and
might be attributable to alterations in the postnatal developmental
trajectory of MOR signaling.},
doi = {10.1093/cercor/bhr202},
eprint = {http://cercor.oxfordjournals.org/cgi/reprint/bhr202v1.pdf},
url = {http://cercor.oxfordjournals.org/cgi/content/abstract/bhr202v1}
}
@ARTICLE{Vollrath2009,
author = {Vollrath, Aaron and Smith, Adam and Craven, Mark and Bradfield, Christopher},
title = {EDGE3: A web-based solution for management and analysis of Agilent
two color microarray experiments},
journal = {BMC Bioinformatics},
year = {2009},
volume = {10},
pages = {280},
number = {1},
abstract = {BACKGROUND:The ability to generate transcriptional data on the scale
of entire genomes has been a boon both in the improvement of biological
understanding and in the amount of data generated. The latter, the
amount of data generated, has implications when it comes to effective
storage, analysis and sharing of these data. A number of software
tools have been developed to store, analyze, and share microarray
data. However, a majority of these tools do not offer all of these
features nor do they specifically target the commonly used two color
Agilent DNA microarray platform. Thus, the motivating factor for
the development of EDGE3 was to incorporate the storage, analysis
and sharing of microarray data in a manner that would provide a means
for research groups to collaborate on Agilent-based microarray experiments
without a large investment in software-related expenditures or extensive
training of end-users.RESULTS:EDGE3 has been developed with two major
functions in mind. The first function is to provide a workflow process
for the generation of microarray data by a research laboratory or
a microarray facility. The second is to store, analyze, and share
microarray data in a manner that doesn't require complicated software.
To satisfy the first function, EDGE3 has been developed as a means
to establish a well defined experimental workflow and information
system for microarray generation. To satisfy the second function,
the software application utilized as the user interface of EDGE3
is a web browser. Within the web browser, a user is able to access
the entire functionality, including, but not limited to, the ability
to perform a number of bioinformatics based analyses, collaborate
between research groups through a user-based security model, and
access to the raw data files and quality control files generated
by the software used to extract the signals from an array image.CONCLUSION:Here,
we present EDGE3, an open-source, web-based application that allows
for the storage, analysis, and controlled sharing of transcription-based
microarray data generated on the Agilent DNA platform. In addition,
EDGE3 provides a means for managing RNA samples and arrays during
the hybridization process. EDGE3 is freely available for download
at http://edge.oncology.wisc.edu/.},
doi = {10.1186/1471-2105-10-280},
issn = {1471-2105},
pubmedid = {19732451},
url = {http://www.biomedcentral.com/1471-2105/10/280}
}
@ARTICLE{Volz2007,
author = {Volz, Tassilo and Lutgehetmann, Marc and Wachtler, Paul and Jacob,
Anna and Quaas, Alexander and Murray, John M. and Dandri, Maura and
Petersen, Joerg},
title = {Impaired Intrahepatic Hepatitis B Virus Productivity Contributes
to Low Viremia in Most HBeAg-Negative Patients},
journal = {Gastroenterology},
year = {2007},
volume = {133},
pages = {843--852},
number = {3},
month = sep,
abstract = {Background & Aims: Knowledge of factors regulating transcriptional
activity of hepatitis B virus (HBV) covalently closed circular DNA
(cccDNA) may help in understanding mechanisms of viral decay and
how these processes are thwarted in chronically HBV-infected patients.
Methods: Liver biopsies from 119 treatment-naive chronically infected
patients (42 HBeAg-positive and 77 HBeAg-negative) were determined
for HBV transcriptional and replicative activity. Results: Significantly
lower median serum HBV DNA (-4 log), intrahepatic HBV DNA (-2 log),
and cccDNA (-1 log) amounts were measured in HBeAg-negative versus
HBeAg-positive patients. Despite a good correlation found between
intrahepatic amounts of progeny virions and serum HBV DNA in all
patients, cccDNA levels did not correlate with serum titers in HBeAg-negative
individuals. Analysis of HBV RNA transcripts showed that impaired
virion productivity in HBeAg-negative individuals was due to lower
steady-state levels of pregenomic RNA produced per cccDNA. Interestingly,
preS/S RNA levels and serum HBsAg concentrations did not differ between
HBeAg-positive and HBeAg-negative patients when normalized for cccDNA
contents, showing that subviral particle production was not impaired
in HBeAg-negative patients and correlated with cccDNA levels. Although
the majority of HBeAg-negative individuals harbored cccDNA with common
precore and/or basal core promoter mutations, occurrence of these
variants was not responsible for reduced viral replication. Instead,
replacement of wild-type cccDNA with core promoter mutants reestablished
high virion productivity. Conclusions: Lower viremia in HBeAg-negative
individuals is not only due to lower cccDNA content but also to impaired
virion productivity, which can arise without emergence of HBeAg variants
and without affecting HBsAg production.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4P40KHH-6/2/fc5d3b470f3771e050f8639b9c1207ff}
}
@ARTICLE{VonHoff2010,
author = {Von Hoff, Daniel D. and Stephenson, Joseph J., Jr and Rosen, Peter
and Loesch, David M. and Borad, Mitesh J. and Anthony, Stephen and
Jameson, Gayle and Brown, Susan and Cantafio, Nina and Richards,
Donald A. and Fitch, Tom R. and Wasserman, Ernesto and Fernandez,
Cristian and Green, Sylvan and Sutherland, William and Bittner, Michael
and Alarcon, Arlet and Mallery, David and Penny, Robert},
title = {Pilot Study Using Molecular Profiling of Patients' Tumors to Find
Potential Targets and Select Treatments for Their Refractory Cancers},
journal = {J. Clin. Oncol.},
year = {2010},
volume = {28},
pages = {4877--4883},
number = {33},
month = nov,
abstract = {PurposeTo compare the progression-free survival (PFS) using a treatment
regimen selected by molecular profiling (MP) of a patient's tumor
with the PFS for the most recent regimen on which the patient had
experienced progression (ie, patient as his own control). Patients
and MethodsPatients with refractory metastatic cancer had tissue
samples submitted for MP in two formats including formalin-fixed
tissue for immunohistochemistry and fluorescent in situ hybridization
assays and immediately frozen tissue for jco_glossary;1408oligonucleotide
microarray (MA) gene expression assays (all performed in a Clinical
Laboratory Improvement Amendments [jco_glossary;1405CLIA] -certified
laboratory). The MP approach was deemed of clinical benefit for the
individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS
on prior therapy) of [≥] 1.3. ResultsIn 86 patients who had MP
attempted, there was a molecular target detected in 84 (98%). Sixty-six
of the 84 patients were treated according to MP results. Eighteen
(27%) of 66 patients had a PFS ratio of [≥] 1.3 (95% CI, 17% to
38%; one-sided, one-sample P = .007). Therefore, the null hypothesis
(that [≤] 15% of this patient population would have a PFS ratio
of [≥] 1.3) was rejected. ConclusionIt is possible to identify
molecular targets in patients' tumors from nine different centers
across the United States. In 27% of patients, the MP approach resulted
in a longer PFS on an MP-suggested regimen than on the regimen on
which the patient had just experienced progression. Issues to be
considered in interpretation of this study include limited prior
experience with patients as their own controls as a study end point
and overall patient attrition.},
comment = {10.1200/JCO.2009.26.5983},
url = {http://jco.ascopubs.org/cgi/content/abstract/28/33/4877}
}
@ARTICLE{VonKrogh2010,
author = {Von Krogh, Kristine and Harjen, Hannah and Almås, Camilla and Zimmer,
Karin E. and Dahl, Ellen and Olsaker, Ingrid and Taubøll, Erik and
Ropstad, Erik and Verhaegen, Steven},
title = {The effect of valproate and levetiracetam on steroidogenesis in forskolin-stimulated
H295R cells},
journal = {Epilepsia},
year = {2010},
volume = {51},
pages = {2280--2288},
number = {11},
abstract = {Summary Purpose:  Endocrine disruptive effects have been frequently
observed in patients using antiepileptic drugs (AEDs). Two different
AEDs, valproate (VPA) and levetiracetam (LEV), were tested in forskolin-stimulated
human adrenal carcinoma (H295R) cells to explore their effect on
steroidogenesis. VPA has a long history as an anticonvulsant and
is linked with many of the endocrine disorders associated with AED
use. LEV is a newer AED, and no endocrine disruptive effects have
been reported in humans to date. Methods:  H295R cells, which are
capable of full steroidogenesis, were stimulated with forskolin and
exposed to either VPA or LEV for 48Â h. Medium was collected and
analyzed for hormone production. For the VPA-exposed cells, steroidogenic
gene expression analysis was also conducted. Results:  VPA exposure
resulted in a significant reduction in progesterone and estradiol
(E2) production, whereas testosterone (T) levels remained unchanged.
There were also significant alterations in expression level for most
genes analyzed. LEV exposure resulted in a minor, but statistically
significant, reduction in T and E2 production. Discussion:  Exposure
of forskolin-stimulated H295R cells to VPA led to an increased T/E2
ratio through a significant decrease in estradiol production. Gene
analysis suggested that VPA affects NR0B1 expression. NR0B1 inhibits
promoters of other genes involved in steroidogenesis, and the altered
expression of NR0B1 might explain the observed down-regulation in
hormone production. The effects of LEV exposure on hormone secretion
were not considered to be biologically significant.},
issn = {1528-1167},
keywords = {Valproate, Levetiracetam, Epilepsy, Steroidogenesis, Endocrine disruption},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1528-1167.2010.02702.x}
}
@ARTICLE{Vonarx2006,
author = {Vonarx, Edward J. and Tabone, Emma K. and Osmond, Megan J. and Anderson,
Heather J. and Kunz, Bernard A.},
title = {Arabidopsis homologue of human transcription factor IIH/nucleotide
excision repair factor p44 can function in transcription and DNA
repair and interacts with AtXPD},
journal = {The Plant Journal},
year = {2006},
volume = {46},
pages = {512--521},
number = {3},
abstract = {Summary Eukaryotic general transcription factor (TF) IIH is composed
of 10 proteins, seven of which are also required for nucleotide excision
repair (NER) of UV radiation-induced DNA damage in human cells and
yeast. Plant homologues of the human TFIIH subunits XPB and XPD that
function in NER have been isolated but none has been shown to operate
in transcription. Here we address the capabilities of Arabidopsis
thaliana AtGTF2H2 and AtXPD, homologues of the essential interacting
human/yeast TFIIH components p44/Ssl1 and XPD/Rad3, respectively.
Expression of AtGTF2H2 or AtXPD cDNAs in yeast ssl1 or rad3 mutants
temperature-sensitive for growth due to thermolabile transcription
of mRNA restored growth and so transcription at the non-permissive
temperature. AtGTF2H2 also complemented the NER deficiency of the
corresponding yeast mutant, as measured by full recovery of UV resistance,
whereas AtXPD did not despite being necessary for NER in Arabidopsis.
UV treatment did not upregulate transcription of AtGTF2H2 or AtXPD
in Arabidopsis. Suppression of a yeast translation initiation defect
by the ssl1-1 mutation was prevented by expression of AtGTF2H2. Deletion
of SSL1 in a yeast strain expressing AtGTF2H2 did not affect growth
or confer UV sensitivity, demonstrating that AtGTF2H2 can perform
all essential transcription functions and UV damage repair duties
of Ssl1 in its absence. Furthermore, AtGTF2H2 interacted with AtXPD
and yeast Rad3, and AtXPD also interacted with yeast Ssl1 in two-hybrid
assays. Our results indicate that AtGTF2H2 can act in transcription
and NER, and suggest that it participates in both processes in Arabidopsis
as part of TFIIH.},
issn = {1365-313X},
keywords = {Arabidopsis thaliana, functional complementation, nucleotide excision
repair, protein interaction, transcription factor IIH, yeast},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2006.02705.x}
}
@ARTICLE{Vong2006,
author = {Vong, Queenie P. and Li, Yunmin and Lau, Yun-Fai Chris and Dym, Martin
and Rennert, Owen M. and Chan, Wai-Yee},
title = {Structural Characterization and Expression Studies of Dby and Its
Homologs in the Mouse},
journal = {J Androl},
year = {2006},
volume = {27},
pages = {653--661},
number = {5},
month = sep,
abstract = {In spite of recent evidence showing the importance of DBY (DEAD-box
RNA helicase Y) in spermatogenesis in human, the biologic role of
its homolog Dby (also known as Ddx3y) in the mouse is less clear.
The present study aims at characterizing the molecular structure
of Dby and comparing its expression with its X- and autosome-linked
homologs in embryonic gonads and developing germ cells in mice. Molecular
cloning by rapid amplification of 3'-cDNA ends showed that the Dby
gene in the mouse gives rise to 2 transcripts that differ only in
the length of the 3'-untranslated region as a consequence of the
use of alternative polyadenylation signals. Measurement by quantitative
real-time polymerase chain reaction showed that both transcripts
were ubiquitously expressed and were present in male germ cells and
Sertoli cells. They were more abundant in type A spermatogonia compared
with pachytene spermatocytes and round spermatids. Expression of
Dby in the embryonic gonad increased from day 10.5 and reached a
peak at day 17.5. The expression level of Dby decreased after birth
and remained low in adult male gonads. Although the level of expression
of Dby was much lower than its X chromosome homolog, Ddx3 (also known
as Ddx3x) in all samples examined, the pattern of expression of the
2 genes was comparable. In contrast, their autosomal homolog, D1Pas1(also
known as PL10), was predominantly expressed in pachytene spermatocytes
and round spermatids. This result is in accord with meiotic sex chromosome
inactivation in that Dby and Ddx are replaced in pachytene spermatocytes
by their autosomal retroposon. These observations indicate that unlike
DBY in humans, the role of Dby in spermatogenesis is less obvious
in the mouse and its biologic activity may be replaced by that of
Ddx3 and D1Pas1.},
url = {http://www.andrologyjournal.org/cgi/content/abstract/27/5/653}
}
@ARTICLE{Vongsangnak2011,
author = {Vongsangnak, Wanwipa and Hansen, Kim and Nielsen, Jens},
title = {Integrated analysis of the global transcriptional response to α-amylase
over-production by Aspergillus oryzae},
journal = {Biotechnology and Bioengineering},
year = {2011},
volume = {108},
pages = {1130--1139},
number = {5},
abstract = {Abstract The filamentous fungus Aspergillus oryzae is an important
microbial cell factory for industrial production of many enzymes,
such as α-amylase. In order to optimize the industrial enzyme production
process, there is a need to understand fundamental processes underlying
enzyme production, here under how enzyme production links to metabolism
through global regulation. Through a genome-scale metabolic network
for integrated analysis of transcriptome data and flux calculation,
we identified key players (genes, enzymes, proteins, and metabolites)
involved in the processes of enzyme synthesis and secretion, nucleotide
metabolism, and amino acid metabolism that can be the potential targets
for improving industrial enzyme production. Bioeng. 2011; 108:1130–1139.
© 2010 Wiley Periodicals, Inc.},
doi = {10.1002/bit.23033},
issn = {1097-0290},
keywords = {Aspergillus oryzae, α-amylase, data integration, systems biology,
enzyme production},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.23033}
}
@ARTICLE{Vongsangnak2009,
author = {Vongsangnak, Wanwipa and Salazar, Margarita and Hansen, Kim and Nielsen,
Jens},
title = {Genome-wide analysis of maltose utilization and regulation in aspergilli},
journal = {Microbiology},
year = {2009},
volume = {155},
pages = {3893--3902},
number = {12},
month = dec,
abstract = {Maltose utilization and regulation in aspergilli is of great importance
for cellular physiology and industrial fermentation processes. In
Aspergillus oryzae, maltose utilization requires a functional MAL
locus, composed of three genes: MALR encoding a regulatory protein,
MALT encoding maltose permease and MALS encoding maltase. Through
a comparative genome and transcriptome analysis we show that the
MAL regulon system is active in A. oryzae while it is not present
in Aspergillus niger. In order to utilize maltose, A. niger requires
a different regulatory system that involves the AmyR regulator for
glucoamylase (glaA) induction. Analysis of reporter metabolites and
subnetworks illustrates the major route of maltose transport and
metabolism in A. oryzae. This demonstrates that overall metabolic
responses of A. oryzae occur in terms of genes, enzymes and metabolites
when the carbon source is altered. Although the knowledge of maltose
transport and metabolism is far from being complete in Aspergillus
spp., our study not only helps to understand the sugar preference
in industrial fermentation processes, but also indicates how maltose
affects gene expression and overall metabolism.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/155/12/3893}
}
@ARTICLE{Vonnahme2006,
author = {Vonnahme, Kimberly A and Redmer, Dale A and Borowczyk, Ewa and Bilski,
Jerzy J and Luther, Justin S and Johnson, Mary Lynn and Reynolds,
Lawrence P and Grazul-Bilska, Anna T},
title = {Vascular composition, apoptosis, and expression of angiogenic factors
in the corpus luteum during prostaglandin F2{alpha}-induced regression
in sheep},
journal = {Reproduction},
year = {2006},
volume = {131},
pages = {1115--1126},
number = {6},
month = jun,
abstract = {Corpora lutea and blood samples were collected from superovulated
ewes 0, 4, 8, 12 and 24 h after prostaglandin F2{alpha} (PGF) analog
injection on day 10 of the estrous cycle. Changes in vascular cell
and fibroblast composition, apoptosis and mRNA expression for several
angiogenic factors in the corpus luteum (CL) were determined. While
peripheral progesterone concentration decreased at 24 h after PGF
injection, CL weight did not change. The area of positive BS-1 lectin
staining (endothelial cell marker), smooth muscle cell actin (SMCA;
pericyte and SMC marker), collagen type 1 (fibroblast marker), and
the rate of cell death changed in luteal tissues after PGF treatment.
In association with these cellular changes, mRNA for several angiogenic
factors including vascular endothelial growth factor (VEGF) and receptors
(Flt and KDR), basic fibroblast growth factor (FGF2) and receptor,
angiopoietin (ANGPT) 1 and receptor Tie-2, endothelial nitric oxide
synthase (NOS3), and angiotensin II receptor 1 (AT1) were altered.
Changes in endothelial cell marker expression were positively correlated
with changes in VEGF and NO systems. In addition, changes in mRNA
expression for VEGF, Flt and KDR were positively correlated with
changes in ANGPT2, Tie-2, and NOS3, indicating a functional relationship.
This data demonstrates that after an initial increase, the endothelial
component of the vascular bed decreases during PGF-induced luteal
regression. However, SMCA expression remained high during luteal
regression, potentially indicating a role of pericytes and vascular
SMC in luteolysis, likely to regulate tissue remodeling and to maintain
the integrity of larger blood vessels. Further, it appears that early
regression may increase collagen type 1 production and/or expression
by fibroblasts. Expression of angiogenic factors is influenced by
PGF-induced luteolysis and may serve to maintain vascular structure
in order to aid luteal regression.},
url = {http://www.reproduction-online.org/cgi/content/abstract/131/6/1115}
}
@ARTICLE{Vonnahme2007,
author = {Vonnahme, K. A. and Zhu, M. J. and Borowicz, P. P. and Geary, T.
W. and Hess, B. W. and Reynolds, L. P. and Caton, J. S. and Means,
W. J. and Ford, S. P.},
title = {Effect of early gestational undernutrition on angiogenic factor expression
and vascularity in the bovine placentome},
journal = {J Anim Sci},
year = {2007},
volume = {85},
pages = {2464--2472},
number = {10},
month = oct,
abstract = {The effect of early gestation maternal undernutrition followed by
realimentation on placentomal vascular growth and angiogenic factor
expression was determined in multiparous beef cows bred to the same
bull. Cows gestating only female fetuses (n = 30) were fed in equal
numbers to meet the NRC requirements (control) or were fed below
the NRC requirements to lose BW (nutrient restricted; NR) from d
30 to 125 of gestation. After slaughter on d 125 of gestation, 10
control and 10 NR cows were necropsied. The remaining NR cows (n
= 5) were then fed to achieve a BCS equal to their control group
contemporaries (n = 5) by d 220 of gestation. All cows were fed the
control diet from d 220 until 250 of gestation, when the remaining
control and NR cows were slaughtered and necropsied. At necropsy,
placentomes were fixed via perfusion of the caruncular and cotyledonary
arteries to determine capillary vascular density. Cotyledonary (fetal
placental) and caruncular (maternal placental) tissues also were
snap-frozen in liquid nitrogen, and mRNA concentrations of vascular
endothelial growth factor and its 2 specific receptors, fms-like
tyrosine kinase and kinase insert domain containing receptor, as
well as placental growth factor, were determined. There was no effect
of diet or day of gestation on the percentage of proliferating caruncular
cells. Although diet did not impact cotyledonary cellular proliferation,
there was an increase (P < 0.05) in the percentage of proliferating
cells on d 250 compared with d 125 of gestation. Nutrient restriction
from d 30 to 125 increased (P [≤] 0.10) placental mRNA concentrations
of placental growth factor and fms-like tyrosine kinase; however,
there was no alteration in vascularity. By d 250 of gestation, NR
cows had increased (P < 0.05) caruncular capillary surface density
and decreased (P < 0.05) cotyledonary capillary area density, capillary
number density, and capillary surface density compared with control
cows. Although nutrient restriction had little effect on placental
vascularity by d 125, upon realimentation, alterations in vascularity
became apparent by d 250 of gestation, suggesting a placental programming
effect.},
url = {http://jas.fass.org/cgi/content/abstract/85/10/2464}
}
@ARTICLE{Vonnahme2008,
author = {Vonnahme, K.A. and Arndt, W.J. and Johnson, M.L. and Borowicz, P.P.
and Reynolds, L.P.},
title = {Effect of Morphology on Placentome Size, Vascularity, and Vasoreactivity
in Late Pregnant Sheep},
journal = {Biol Reprod},
year = {2008},
volume = {79},
pages = {976--982},
number = {5},
month = nov,
abstract = {Ovine placentomes vary in shape, with type A placentomes being concave,
type D convex, and types B and C intermediate in morphology. It has
been speculated that as placentomes advance in type they differ in
vascularity and nutrient transport capacity. Our objective was to
determine cellularity and vascularity measurements, angiogenic factor
expression, and arterial vasoactivity within different morphologic
types of placentomes. On Day 130 of gestation, placentomes were collected
from multiparous ewes (n = 38) and were evaluated for size, cellularity
estimates, angiogenic factor mRNA expression, capillary vascularity
(capillary size, capillary surface density [CSD], capillary number
density [CND], and capillary area density [CAD]), and vasoreactivity
to potassium chloride and angiotensin II. The average weight and
size of type A and B placentomes were less (P < 0.01) than those
of type C and D placentomes. Placentome morphology did not affect
(P [≥] 0.24) cotyledonary or caruncular cellularity estimates
or percentage of cellular proliferation. Placentome morphology affected
(P [≥] 0.41) neither caruncular CAD, CND, CSD, or capillary size
nor cotyledonary CND, CSD, or capillary size. Cotyledonary CAD was
increased (P < 0.01) in type B and D placentomes compared with type
A placentomes. Furthermore, placentome type did not affect (P [≥]
0.06) angiogenic factor gene expression in the cotyledon or the caruncle.
Size, but not morphologic type of placentome, was associated with
greater caruncular artery contractility to potassium chloride and
angiotensin II (P < 0.01 for both). Placentome size, but not morphologic
type, may be important for vascularity and nutrient transfer in the
placenta of the pregnant ewe..},
url = {http://www.biolreprod.org/cgi/content/abstract/79/5/976}
}
@ARTICLE{Voolstra2009,
author = {Voolstra, Christian and Schnetzer, Julia and Peshkin, Leonid and
Randall, Carly and Szmant, Alina and Medina, Mónica},
title = {Effects of temperature on gene expression in embryos of the coral
Montastraea faveolata},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {627},
number = {1},
abstract = {BACKGROUND:Coral reefs are expected to be severely impacted by rising
seawater temperatures associated with climate change. This study
used cDNA microarrays to investigate transcriptional effects of thermal
stress in embryos of the coral Montastraea faveolata. Embryos were
exposed to 27.5°C, 29.0°C, and 31.5°C directly after fertilization.
Differences in gene expression were measured after 12 and 48 hours.RESULTS:Analysis
of differentially expressed genes indicated that increased temperatures
may lead to oxidative stress, apoptosis, and a structural reconfiguration
of the cytoskeletal network. Metabolic processes were downregulated,
and the action of histones and zinc finger-containing proteins may
have played a role in the long-term regulation upon heat stress.CONCLUSIONS:Embryos
responded differently depending on exposure time and temperature
level. Embryos showed expression of stress-related genes already
at a temperature of 29.0°C, but seemed to be able to counteract the
initial response over time. By contrast, embryos at 31.5°C displayed
continuous expression of stress genes. The genes that played a role
in the response to elevated temperatures consisted of both highly
conserved and coral-specific genes. These genes might serve as a
basis for research into coral-specific adaptations to stress responses
and global climate change.},
doi = {10.1186/1471-2164-10-627},
issn = {1471-2164},
pubmedid = {20030803},
url = {http://www.biomedcentral.com/1471-2164/10/627}
}
@ARTICLE{Voolstra2009a,
author = {Voolstra, Christian R. And Schwarz, Jodi A. And Schnetzer, Julia
And Sunagawa, Shinichi And Desalvo, Michael K. And Szmant, Alina
M. And Coffroth, Mary Alice And Medina, Mã“nica},
title = {The host transcriptome remains unaltered during the establishment
of coral–algal symbioses},
journal = {Molecular Ecology},
year = {2009},
volume = {18},
pages = {1823--1833},
number = {9},
abstract = {Abstract Coral reefs are based on the symbiotic relationship between
corals and photosynthetic dinoflagellates of the genus Symbiodinium.
We followed gene expression of coral larvae of Acropora palmata and
Montastraea faveolata after exposure to Symbiodinium strains that
differed in their ability to establish symbioses. We show that the
coral host transcriptome remains almost unchanged during infection
by competent symbionts, but is massively altered by symbionts that
fail to establish symbioses. Our data suggest that successful coral–algal
symbioses depend mainly on the symbionts' ability to enter the host
in a stealth manner rather than a more active response from the coral
host.},
issn = {1365-294X},
keywords = {algae, coral, host, symbiont, symbiosis, transcriptome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2009.04167.x}
}
@ARTICLE{Voolstra2009b,
author = {Voolstra, Christian R. and Sunagawa, Shinichi and Schwarz, Jodi A.
and Coffroth, Mary Alice and Yellowlees, Dave and Leggat, William
and Medina, Mónica},
title = {Evolutionary analysis of orthologous cDNA sequences from cultured
and symbiotic dinoflagellate symbionts of reef-building corals (Dinophyceae:
Symbiodinium)},
journal = {Comparative Biochemistry and Physiology Part D: Genomics and Proteomics},
year = {2009},
volume = {4},
pages = {67--74},
number = {2},
month = jun,
abstract = {Dinoflagellates are ubiquitous marine and freshwater protists. The
endosymbiotic relationship between dinoflagellates of the genus Symbiodinium
(also known as zooxanthellae) and corals forms the basis of coral
reefs. We constructed and analyzed a cDNA library from a cultured
Symbiodinium species clade A (CassKB8). The majority of annotated
ESTs from the Symbiodinium sp. CassKB8 library cover metabolic genes.
Most of those belong to either carbohydrate or energy metabolism.
In addition, components of extracellular signal transduction pathways
and genes that play a role in cell-cell communication were identified.
In a subsequent analysis, we determined all orthologous cDNA sequences
between this library (1,484 unique sequences) and a library from
a Symbiodinium species clade C (C3) (3,336 unique sequences) that
was isolated directly from its symbiotic host. A set of 115 orthologs
were identified between Symbiodinium sp. CassKB8 and Symbiodinium
sp. C3. These orthologs were subdivided into three groups that show
different characteristics and functions: conserved across eukaryotes
(CE), dinoflagellate-specific (DS) and Symbiodinium-specific (SS).
Orthologs conserved across eukaryotes are mainly comprised of housekeeping
genes, photosynthesis-related transcripts and metabolic proteins,
whereas the function for most of the dinoflagellate-specific orthologs
remains unknown. A dN/dS analysis identified the highest ratio in
a Symbiodinium-specific ortholog and evidence for positive selection
in a dinoflagellate-specific gene. Evolution of genes and pathways
in different dinoflagellates seems to be affected by different lifestyles,
and a symbiotic lifestyle may affect population structure and strength
of selection. This study is the first evolutionary comparative analysis
of orthologs from two coral dinoflagellate symbionts.},
issn = {1744-117X},
keywords = {cDNA library, Dinoflagellate, Ortholog comparison, Symbiosis, Zooxanthellae},
url = {http://www.sciencedirect.com/science/article/B7XM1-4V3548J-2/2/683de672007eb6e365629b74f86c2473}
}
@ARTICLE{Voss2011,
author = {Voss, Bjorn and Meinecke, Linda and Kurz, Thorsten and Al-Babili,
Salim and Beck, Christoph F. and Hess, Wolfgang R.},
title = {Hemin and Magnesium-Protoporphyrin IX Induce Global Changes in Gene
Expression in Chlamydomonas reinhardtii},
journal = {Plant Physiology},
year = {2011},
volume = {155},
pages = {892--905},
number = {2},
month = feb,
abstract = {Retrograde signaling is a pathway of communication from mitochondria
and plastids to the nucleus in the context of cell differentiation,
development, and stress response. In Chlamydomonas reinhardtii, the
tetrapyrroles magnesium-protoporphyrin IX and heme are only synthesized
within the chloroplast, and they have been implicated in the retrograde
control of nuclear gene expression in this unicellular green alga.
Feeding the two tetrapyrroles to Chlamydomonas cultures was previously
shown to transiently induce five nuclear genes, three of which encode
the heat shock proteins HSP70A, HSP70B, and HSP70E. In contrast,
controversial results exist on the possible role of magnesium-protoporphyrin
IX in the repression of genes for light-harvesting proteins in higher
plants, raising the question of how important this mode of regulation
is. Here, we used genome-wide transcriptional profiling to measure
the global impact of these tetrapyrroles on gene regulation and the
scope of the response. We identified almost 1,000 genes whose expression
level changed transiently but significantly. Among them were only
a few genes for photosynthetic proteins but several encoding enzymes
of the tricarboxylic acid cycle, heme-binding proteins, stress-response
proteins, as well as proteins involved in protein folding and degradation.
More than 50% of the latter class of genes was also regulated by
heat shock. The observed drastic fold changes at the RNA level did
not correlate with similar changes in protein concentrations under
the tested experimental conditions. Phylogenetic profiling revealed
that genes of putative endosymbiontic origin are not overrepresented
among the responding genes. This and the transient nature of changes
in gene expression suggest a signaling role of both tetrapyrroles
as secondary messengers for adaptive responses affecting the entire
cell and not only organellar proteins.},
comment = {10.1104/pp.110.158683},
url = {http://www.plantphysiol.org/cgi/content/abstract/155/2/892}
}
@ARTICLE{Voss2006,
author = {Voss, Kenneth A. and Liu, Jie and Anderson, Steven P. and Dunn, Corrie
and Miller, J. David and Owen, Joy R. and Riley, Ronald T. and Bacon,
Charles W. and Corton, J. Christopher},
title = {Toxic Effects of Fumonisin in Mouse Liver Are Independent of the
Peroxisome Proliferator-Activated Receptor {alpha}},
journal = {Toxicol. Sci.},
year = {2006},
volume = {89},
pages = {108--119},
number = {1},
month = jan,
abstract = {Fumonisin mycotoxins occur worldwide in corn and corn-based foods.
Fumonisin B1 (FB1) is a rodent liver carcinogen and suspected human
carcinogen. It inhibits ceramide synthase and increases tissue sphinganine
(Sa) and sphingosine (So) concentrations. Events linking disruption
of sphingolipid metabolism and fumonisin toxicity are not fully understood;
however, Sa and So were shown to bind mouse recombinant peroxisome
proliferator-activated receptor {alpha} (PPAR{alpha}) in vitro. To
investigate the role of PPAR{alpha} in fumonisin hepatotoxicity in
vivo, wild-type (WT) and PPAR{alpha}-null mice were fed control diets
or diets containing 300 ppm FB1, Fusarium verticillioides culture
material (CM) providing 300 ppm FB1, or 500 ppm of the peroxisome
proliferator WY-14,643 (WY) for 1 week. WY-fed WT mice exhibited
hepatomegaly, an effect not found in WY-fed PPAR{alpha}-null mice,
and WY did not change liver sphingoid base concentrations in either
strain. Hepatotoxicity found in FB1- and CM-fed WT and PPAR{alpha}-null
mice was similar, qualitatively different from that found in WY-treated
animals, and characterized by increased Sa concentration, apoptosis,
and cell proliferation. Transcript profiling using oligonucleotide
arrays showed that CM and FB1 elicited similar expression patterns
of genes involved in cell proliferation, signal transduction, and
glutathione metabolism that were different from that altered by WY.
Real-time RT-PCR analysis of gene expression demonstrated PPAR{alpha}-dependence
of lipid metabolism gene expression in WY-treated mice, whereas PPAR{alpha}-independent
alterations of genes in lipid metabolism, and other categories, were
found in CM- and FB1-fed mice. Together, these findings demonstrate
that FB1- and CM-induced hepatotoxicity in mice does not require
PPAR{alpha}.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/89/1/108}
}
@ARTICLE{Voss2011a,
author = {Voss, Thorsten and Kruhoffer, Mogens and Nielsen, Karsten Bork and
Vial, Alexander},
title = {Abstract B32: High-throughput solution for microRNA (miRNA) isolation
from stabilized whole blood in a GLP setting: Development and comparison
to established procedures.},
journal = {Mol. Cancer Ther.},
year = {2011},
volume = {10},
pages = {B32},
number = {11_MeetingAbstracts},
doi = {10.1158/1535-7163.TARG-11-B32},
url = {http://mct.aacrjournals.org}
}
@ARTICLE{Vosslamber2011,
author = {Vosslamber, Saskia and Raterman, Hennie G and van der Pouw Kraan,
Tineke C T M and Schreurs, Marco W J and von Blomberg, B Mary E and
Nurmohamed, Michael T and Lems, Willem F and Dijkmans, Ben A C and
Voskuyl, Alexandre E and Verweij, Cornelis L},
title = {Pharmacological induction of interferon type I activity following
treatment with rituximab determines clinical response in rheumatoid
arthritis},
journal = {Ann Rheum Dis},
year = {2011},
volume = {70},
pages = {1153--1159},
number = {6},
month = jun,
abstract = {ObjectiveDespite the fact that rituximab depletes B cells in all treated
patients with RA, not all patients show a favourable clinical response.
The goal of this study was to provide insight into pharmacological
changes in peripheral blood that are associated with clinical response
to rituximab. MethodsGene expression profiling was performed on peripheral
blood RNA of 13 patients with RA (test group) using Illumina HumanHT
beadchip microarrays. An independent group of nine patients was used
for validation using TaqMan quantitative PCR. Clinical responder
status was determined after 6 months using change in 28-joint Disease
Activity Score ({Delta}DAS28) and European League Against Rheumatism
(EULAR) response criteria. Significance analysis of microarrays and
ontology analysis were used for data analysis and interpretation.
ResultsPharmacogenomic analyses demonstrated marked interindividual
differences in the pharmacological responses at 3 and 6 months after
start of treatment with rituximab. Interestingly, only differences
in the regulation of type I interferon (IFN)-response genes after
3 months correlated with the {Delta}DAS28 response. Good responders
({triangleup}DAS>1.2; n=7) exhibited a selective increase in the
expression of type I IFN-response genes, whereas this activity was
unchanged or hardly changed in non-responders ({triangleup}DAS<1.2;
n=6) (p=0.0040 at a cut-off of 1.1-fold induction). Similar results
were obtained using EULAR response criteria. These results were validated
in an independent cohort of nine patients (five non-responders and
four responders, p=0.0317). ConclusionsA good clinical response to
rituximab in RA is associated with a selective drug-induced increase
in type I IFN-response activity in patients with RA. This finding
may provide insight in the biological mechanism underlying the therapeutic
response to rituximab.},
comment = {10.1136/ard.2010.147199},
url = {http://ard.bmj.com/cgi/content/abstract/70/6/1153}
}
@ARTICLE{Votavova2011,
author = {H. Votavova and M. Dostalova Merkerova and K. Fejglova and A. Vasikova
and Z. Krejcik and A. Pastorkova and N. Tabashidze and J. Topinka
and M. Veleminsky Jr. and R.J. Sram and R. Brdicka},
title = {Transcriptome alterations in maternal and fetal cells induced by
tobacco smoke},
journal = {Placenta},
year = {2011},
volume = {32},
pages = {763 - 770},
number = {10},
abstract = {Objectives Maternal smoking has a negative effect on all stages of
pregnancy. Tobacco smoke-related defects are well established at
the clinical level; however, less is known about molecular mechanisms
underlying these pathologic conditions. We thus performed a comprehensive
analysis of transcriptome alterations induced by smoking in maternal
and fetal cells. Study design Samples of peripheral blood (PB), placenta
(PL), and cord blood (UCB) were obtained from pregnant smokers (n = 20)
and gravidas without significant exposure to tobacco smoke (n = 52).
Gene expression profiles were assayed by Illumina Expression Beadchip
v3 for analysis of 24,526 transcripts. The quantile method was used
for normalization. Differentially expressed genes were analyzed in
the Limma package and the P-values were corrected for multiple testing.
Unsupervised hierarchical clustering was performed using average
linkage and Euclidean distance. The enrichment of deregulated genes
in biological processes was analyzed in DAVID database. Results Comparative
analyses defined significant deregulation of 193 genes in PB, 329
genes in PL, and 49 genes in UCB of smokers. The deregulated genes
were mainly related to xenobiotic metabolism, oxidative stress, inflammation,
immunity, hematopoiesis, and vascularization. Notably, functional
annotation of the affected genes identified several deregulated pathways
associated with autoimmune diseases in the newborns of smokers. Conclusions
The study demonstrated maternal smoking causes significant changes
in transcriptome of placental and fetal cells that deregulate numerous
biological processes important for growth and development of the
fetus. An activation of fetal CYP genes showed a limited ability
of the placenta to modulate toxic effects of maternal tobacco use.},
doi = {10.1016/j.placenta.2011.06.022},
issn = {0143-4004},
keywords = {Maternal smoking},
url = {http://www.sciencedirect.com/science/article/pii/S0143400411002438}
}
@ARTICLE{Vouk2011,
author = {Katja Vouk and Tina Å muc and Christina Guggenberger and Martina
RibiÄ?-Pucelj and Jasna Å inkovec and Bettina Husen and Hubert Thole
and Pieter Houba and Claudia Thaete and Jerzy Adamski and Tea Lanišnik
Rižner},
title = {Novel estrogen-related genes and potential biomarkers of ovarian
endometriosis identified by differential expression analysis},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2011},
volume = {125},
pages = {231 - 242},
number = {3–5},
abstract = {In the search for novel biomarkers of endometriosis, we selected 152
genes from the GeneLogic database based on results of genome-wide
expression analysis of ovarian endometriosis, plus 20 genes related
to estrogen metabolism and action. We then performed low-density
array analysis of these 172 genes on 11 ovarian endometriosis samples
and 9 control endometrium samples. Principal component analysis of
the gene expression levels showed clear separation between the endometriosis
and control groups. We identified 78 genes as differentially expressed.
Based on Ingenuity pathway analysis, these differentially expressed
genes were arranged into groups according to biological function.
These analyses revealed that 32 differentially expressed genes are
estrogen related, 23 of which have not been reported previously in
connection with endometriosis. Functional annotation showed that
25 and 22 genes are associated with the biological terms “secreted�
and “extracellular region�, respectively. Differential expression
of 4 out of 5 genes related to estrogen metabolism and action (ESR1,
ESR2, PGR and BGN) was also confirmed by immunohistochemistry. Our
study thus reveals differential expression of several genes that
have not previously been associated with endometriosis and that encode
potential novel biomarkers and drug targets.},
doi = {10.1016/j.jsbmb.2011.03.010},
issn = {0960-0760},
keywords = {Steroids},
url = {http://www.sciencedirect.com/science/article/pii/S0960076011000537}
}
@ARTICLE{Voznesensky2004,
author = {Voznesensky, Maria and Lenz, Petra H. and Spanings-Pierrot, Céline
and Towle, David W.},
title = {Genomic approaches to detecting thermal stress in Calanus finmarchicus
(Copepoda: Calanoida)},
journal = {Journal of Experimental Marine Biology and Ecology},
year = {2004},
volume = {311},
pages = {37--46},
number = {1},
month = nov,
abstract = {Zooplankton may be subjected to physiological stress as they encounter
rapid and large changes in temperature through vertical migration
or transfer into different water masses. Induction of one or more
heat shock proteins (hsp) is a common protective response to thermal
stress in organisms. We looked for evidence for such a response in
Calanus finmarchicus. We compared hsp70 expression in copepods exposed
to temperature stress with that for non-stressed controls. Partial
sequences of the amplified cDNA product were obtained and aligned
with known hsp70 sequences to establish the identity of the heat
shock protein. In one experiment, animals were transferred from their
collection temperature (8 °C) to 20 °C for 30 min, and then returned
to 8 °C for 4 h before sampling for gene expression levels. In another,
the animals were exposed to 18 °C over 48 h before sampling for molecular
analysis. A four-fold induction of hsp70 was measured in both groups
of heat shocked animals using quantitative real time polymerase chain
reaction (PCR). The experimental temperatures, although high for
C. finmarchicus, are within the range of temperatures experienced
by this species in their habitat. In addition to confirming an hsp70-mediated
response in C. finmarchicus, the findings suggest that a recent history
of thermal stress may be assessed in natural populations through
a routine molecular assay.},
issn = {0022-0981},
keywords = {Gene expression, Hsp70, Temperature, Stress},
url = {http://www.sciencedirect.com/science/article/B6T8F-4CRY9K8-1/2/cca060ac39fa33f08688b32d8c954429}
}
@ARTICLE{Vrancic2011,
author = {Vran?i?, M. and Banjanac, M. and Nuji?, K. and Bosnar, M. and Murati,
T. and Muni?, V. and Polan?ec, D. Stupin and Belamarić, D. and Parnham,
M. J. and Haber, V.Erakovi?},
title = {Azithromycin distinctively modulates classical activation of human
monocytes in vitro},
journal = {British Journal of Pharmacology},
year = {2011},
volume = {na},
pages = {no--no},
abstract = {Background and purpose:Â Azithromycin has been reported to modify
activation of macrophages towards the M2 phenotype. We sought to
identify the potential mechanisms involved in this modulatory effect
of the macrolide on human monocytes, classically activated in vitro
with interferon-γ (IFN-γ) and lipopolysaccharide (LPS).Experimental
approach: Human blood monocytes were primed with IFN-γ (1 ng/ml)
for 24 h and then activated with LPS (1 ng/ml) for 24 h. Azithromycin,
anti-inflammatory and lysosome affecting agents to be tested were
added 2 h before IFN-γ. Cytokine and chemokine expression was determined
by QPCR and protein release by ELISA. Signalling molecules were determined
by Western blotting and transcription factor activation quantified
with a DNA-binding ELISA kit.Key results: Azithromycin (1.5 –
50 µM) dose-dependently inhibited gene expression and/or release
of the M1 macrophage markers CCR7, CXCL11 and IL-12p70, but enhanced
CCL2, without altering TNFα or IL-6. At the same time, azithromycin
enhanced the gene expression and/or release of the M2 macrophage
markers IL-10 and CCL18, as well as the pan-monocyte marker CD163,
but inhibited CCL22. The TLR4 signalling pathway was modulated, leading
to down-regulation of NFκB and STAT1 transcription factors. The
inhibitory profile of azithromycin differed from that of dexamethasone,
the PDE4 inhibitor, roflumilast, and the p38 kinase inhibitor, SB203580,
but showed similarity to that of the lysosomotropic drug, chloroquine.
Effects of concanamycin and NH4Cl, which also act on lysosomes, differed
significantly.Conclusions and implications:Â Azithromycin modulates
classical activation of human monocytes by inhibition of TLR4-mediated
signalling and possible effects on lysosomal function, and generates
a mediator expression profile that differs from that of monocyte/macrophage
phenotypes so far described.},
doi = {10.1111/j.1476-5381.2011.01576.x},
issn = {1476-5381},
keywords = {azithromycin, dexamethasone, roflumilast, SB203580, human monocyte,
human macrophage, classical activation, anti-inflammatory drug, lysosome
affecting agent, TLR4 signalling},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1476-5381.2011.01576.x}
}
@ARTICLE{Vrancken2011,
author = {Vrancken, Gino and De Vuyst, Luc and Rimaux, Tom and Allemeersch,
Joke and Weckx, Stefan},
title = {Adaptation of Lactobacillus plantarum IMDO 130201, a Wheat Sourdough
Isolate, to Growth in Wheat Sourdough Simulation Medium at Different
pH Values through Differential Gene Expression},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {3406--3412},
number = {10},
month = may,
abstract = {Sourdough is a very competitive and challenging environment for microorganisms.
Usually, a stable microbiota composed of lactic acid bacteria (LAB)
and yeasts dominates this ecosystem. Although sourdough is rich in
carbohydrates, thus providing an ideal environment for microorganisms
to grow, its low pH presents a particular challenge. The nature of
the adaptation to this low pH was investigated for Lactobacillus
plantarum IMDO 130201, an isolate from a laboratory wheat sourdough
fermentation. Batch fermentations were carried out in wheat sourdough
simulation medium, and total RNA was isolated from mid-exponential-growth-phase
cultures, followed by differential gene expression analysis using
a LAB functional gene microarray. At low pH values, an increased
expression of genes involved in peptide and amino acid metabolism
was found as well as that of genes involved in plantaricin production
and lipoteichoic acid biosynthesis. The results highlight cellular
mechanisms that allow L. plantarum to function at a low environmental
pH.},
comment = {10.1128/AEM.02668-10},
url = {http://aem.asm.org/cgi/content/abstract/77/10/3406}
}
@ARTICLE{Vranken2008,
author = {Vranken, Ilse and De Visscher, Geofrey and Lebacq, An and Verbeken,
Erik and Flameng, Willem},
title = {The recruitment of primitive Lin- Sca-1+, CD34+, c-kit+ and CD271+
cells during the early intraperitoneal foreign body reaction},
journal = {Biomaterials},
year = {2008},
volume = {29},
pages = {797--808},
number = {7},
month = mar,
abstract = {Implanted materials, such as medical devices, provoke the body to
initiate an inflammatory reaction, known as the foreign body reaction
(FBR), which causes several complications for example in hip prostheses,
silicone implants, peritoneal dialysis catheters and left ventricular
assist devices. FBR is initiated by macrophage adherence and results
in granulation tissue formation. The early immunobiology and development
of this tissue is not completely understood, but there are indications
from related myofibroblast-forming diseases such as vascular repair
and fibrosis that primitive stem cells also play a role in the formation
of FBR-tissue. To investigate this, acellular photo-oxidized bovine
pericardium patches were implanted intraperitoneally in rats and
retrieved at time-points ranging from 6 h to 7 days. A significant
fraction of Sca-1+ (6 h-2 days), c-kit+, CD34+ and CD271+ (2-3 days)
stem/progenitor cells were detected. Colony-forming and differentiation
capacity of the primitive stem cells into adipo-, osteo-, and myofibroblasts
were shown. The presence of these primitive cells and their myofibroblastic
differentiation potential were also confirmed at RNA level. The identification
of specific primitive cells during FBR may have important implications
for the inflammatory responses to inert materials and their use in
tissue prostheses.},
issn = {0142-9612},
keywords = {Foreign body response, Inflammation, Cell adhesion, Primitive cell},
url = {http://www.sciencedirect.com/science/article/B6TWB-4R70K2M-3/2/3bf68bcb99e9c663c5cd010b6b179810}
}
@ARTICLE{Vries-vanderWeij2009,
author = {de Vries-van der Weij, Jitske and de Haan, Willeke and Hu, Lihui
and Kuif, Maarten and Oei, H. Ling D. W. and van der Hoorn, Jose
W. A. and Havekes, Louis M. and Princen, Hans M. G. and Romijn, Johannes
A. and Smit, Johannes W. A. and Rensen, Patrick C. N.},
title = {Bexarotene Induces Dyslipidemia by Increased Very Low-Density Lipoprotein
Production and Cholesteryl Ester Transfer Protein-Mediated Reduction
of High-Density Lipoprotein},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {2368--2375},
number = {5},
month = may,
abstract = {A common dose-limiting side effect of treatment with the retinoid
X receptor agonist bexarotene is dyslipidemia. We evaluated the effects
of bexarotene on plasma lipid metabolism in patients with metastatic
differentiated thyroid carcinoma and investigated the underlying
mechanism(s) in apolipoprotein (APO) E*3-Leiden mice without (E3L)
and with human cholesteryl ester transfer protein (CETP; E3L.CETP).
To this end, 10 patients with metastatic differentiated thyroid carcinoma
were treated with bexarotene (300 mg/d) for 6 wk. Bexarotene increased
plasma triglyceride (TG; +150%), primarily associated with very low-density
lipoprotein (VLDL), and raised plasma total cholesterol (+50%). However,
whereas bexarotene increased VLDL-cholesterol (C) and low-density
lipoprotein (LDL)-C (+63%), it decreased high-density lipoprotein
(HDL)-C (-30%) and tended to decrease apoAI (-18%) concomitant with
an increase in endogenous CETP activity (+44%). To evaluate the cause
of the bexarotene-induced hypertriglyceridemia and the role of CETP
in the bexarotene-induced shift in cholesterol distribution, E3L
and E3L.CETP mice were treated with bexarotene through dietary supplementation
[0.03% (wt/wt)]. Bexarotene increased VLDL-associated TG in both
E3L (+47%) and E3L.CETP (+29%) mice by increasing VLDL-TG production
(+68%). Bexarotene did not affect the total cholesterol levels or
distribution in E3L mice but increased VLDL-C (+11%) and decreased
HDL-C (-56%) as well as apoAI (-31%) in E3L.CETP mice, concomitant
with increased endogenous CETP activity (+41%). This increased CETP
activity by bexarotene-treatment is likely due to the increase in
VLDL-TG, a CETP substrate that drives CETP activity. In conclusion,
bexarotene causes combined dyslipidemia as reflected by increased
TG, VLDL-C, and LDL-C and decreased HDL-C, which is the result of
an increased VLDL-TG production that causes an increase of the endogenous
CETP activity.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/5/2368}
}
@ARTICLE{Vriezen2008,
author = {Vriezen, Wim H. and Feron, Richard and Maretto, Fabio and Keijman,
Jasper and Mariani, Celestina},
title = {Changes in tomato ovary transcriptome demonstrate complex hormonal
regulation of fruit set},
journal = {New Phytologist},
year = {2008},
volume = {177},
pages = {60--76},
number = {1},
abstract = {Summary * • Plant hormones are considered to be important mediators
of the fruit developmental signal after pollination. The role of
phytohormones in tomato (Solanum lycopersicum) fruit set was investigated
here. * • Transcriptome analysis of ovaries was performed using
two complementary approaches: cDNA–amplified fragment length polymorphism
(AFLP) and microarray analysis. * • The gene expression profiles
obtained suggest that, in addition to auxin and gibberellin, ethylene
and abscisic acid (ABA) are involved in regulating fruit set. Before
fruit development, many genes involved in biotic and abiotic responses
are active in the ovary. In addition, genes involved in ethylene
and ABA biosynthesis were strongly expressed, suggesting relatively
high ethylene and ABA concentrations before fruit set. Induction
of fruit development, either by pollination or by gibberellin application,
attenuated expression of all ethylene and ABA biosynthesis and response
genes within 24 h. * • It is proposed that the function of ABA
and ethylene in fruit set might be antagonistic to that of auxin
and gibberellin in order to keep the ovary in a temporally protected
and dormant state; either to protect the ovary tissue or to prevent
fruit development before pollination and fertilization occur.},
issn = {1469-8137},
keywords = {dormancy, hormonal cross-talk, ovary transcriptome analysis, phytohormones,
tomato (Solanum lycopersicum) fruit set},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2007.02254.x}
}
@ARTICLE{Vrljicak2010,
author = {Vrljicak, Pavle and Chang, Alex C. Y. and Morozova, Olena and Wederell,
Elizabeth D. and Niessen, Kyle and Marra, Marco A. and Karsan, Aly
and Hoodless, Pamela A.},
title = {Genomic analysis distinguishes phases of early development of the
mouse atrio-ventricular canal},
journal = {Physiol Genomics},
year = {2010},
volume = {40},
pages = {150--157},
number = {3},
month = feb,
abstract = {Valve formation during embryonic heart development involves a complex
interplay of regional specification, cell transformations, and remodeling
events. While many studies have addressed the role of specific genes
during this process, a global understanding of the genetic basis
for the regional specification and development of the heart valves
is incomplete. We have undertaken genome-wide transcriptional profiling
of the developing heart valves in the mouse. Four Serial Analysis
of Gene Expression libraries were generated and analyzed from the
mouse atrio-ventricular canal (AVC) at embryonic days 9.5-12.5, covering
the stages from initiation of endothelial to mesenchymal transition
(EMT) through to the beginning of endocardial cushion remodeling.
We identified 14 distinct temporal patterns of gene expression during
AVC development. These were associated with specific functions and
signaling pathway members. We defined the temporal distribution of
mesenchyme genes during the EMT process and of specific Notch and
transforming growth factor-{beta} targets. This work provides the
first comprehensive temporal dataset during the formation of heart
valves. These results identify molecular signatures that distinguish
different phases of early heart valve formation allowing gene expression
and function to be further investigated.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/40/3/150}
}
@ARTICLE{Vrolix2011,
author = {Vrolix, Kathleen and Niks, Erik H. and Le Panse, Rozen and van Ostaijen-ten
Dam, Monique M. and Muris, Anne-Hilde and Jol-van der Zijde, Cornelia
M. and van Tol, Maarten J.D. and Losen, Mario and Molenaar, Peter
C. and van Zoelen, Everardus J.J. and Berrih-Aknin, Sonia and De
Baets, Marc H. and Verschuuren, Jan J.G.M. and Martínez-Martínez,
Pilar},
title = {Reduced thymic expression of ErbB receptors without auto-antibodies
against synaptic ErbB in myasthenia gravis},
journal = {Journal of Neuroimmunology},
year = {2011},
volume = {232},
pages = {158--165},
number = {1-2},
month = mar,
abstract = {In myasthenia gravis (MG), the neuromuscular transmission is impaired
mainly by auto-antibodies against the acetylcholine receptor (AChR)
or MuSK. In about 5% of the MG patients, however, the auto-antigen
is still unknown. We investigated whether these idiopathic MG patients
(iMG) have auto-antibodies against ErbB proteins, which influence
the AChR density at the NMJ. Our results show reduced mRNA expression
levels of ErbB4 in thymus tissue of iMG patients compared to AChR-MG
and non-MG patients, but we could not detect anti-ErbB antibodies
in sera of iMG patients. Therefore, our results do not support a
role for ErbB receptors as auto-antigens in iMG patients.},
issn = {0165-5728},
keywords = {Myasthenia gravis, Auto-antibodies, Neuromuscular junction, ErbB},
url = {http://www.sciencedirect.com/science/article/pii/S0165572810004741}
}
@ARTICLE{Vu2008,
author = {Vu, Binh V. and Litvinov, Dmitri and Willson, Richard C.},
title = {Gold Nanoparticle Effects in Polymerase Chain Reaction: Favoring
of Smaller Products by Polymerase Adsorption},
journal = {Analytical Chemistry},
year = {2008},
volume = {80},
pages = {5462-5467},
number = {14},
note = {PMID: 18558773},
doi = {10.1021/ac8000258},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac8000258},
url = {http://pubs.acs.org/doi/abs/10.1021/ac8000258}
}
@ARTICLE{Vuaroqueaux2005,
author = {Vuaroqueaux, Vincent and Labuhn, Martin and Urban, Patrick and Wight,
Edward and Furstenberger, Gregor and Dieterich, Holger and Eppenberger,
Urs and Eppenberger-Castori, Serenella},
title = {Identification of breast cancer patients at minimal risk by means
of quantitative RT-PCR},
journal = {AACR Meeting Abstracts},
year = {2005},
volume = {2005},
pages = {735--},
number = {1},
month = apr,
abstract = {Introduction: It is today accepted that tumor biology plays a major
role in tumor progression and aggressiveness. The biology of breast
cancer (BC) is quite well understood and depends on the equilibrium
between activators and inhibitors of different pathways and their
interactions. Therefore, modern diagnostic tools detecting expression
levels of relevant markers are required. For this purpose we developed
a system able to detect simultaneously the quantitative RNA expression
levels of more than 70 genes. Material and Methods: The molecular
profile was assessed in a series of 317 primary BC patients. In this
collective, 60 patients received no therapy and 258 patients received
adjuvant therapy (hormone therapy n=136, chemotherapy n=72; Combined
therapies n=51). 77% of the patients were older than 50 years, 51%
were nodal negative, 29% experienced disease recurrence within 80
months. RNA was extracted using RNeasy kit (Qiagen). RNA quality
and quantity was tested on the Bioanalyzer 2100 (Agilent). All genes
were examined using the Sybr Green I method with Taqman 7000 (Applied-Biosystems).
Results: Statistical evaluation of the detected genes in the subset
of 60 patients who did not receive adjuvant treatment, revealed that
15 patients (25%) were at minimal risk -no recurrence within the
observation time- (P<0.001). The developed algorithm was then validated
in the remaining 258 cases. Out of 67 patients (21%) with tumor expressing
the "good prognosis" molecular profile 6 patients relapsed within
80 months. The results were compared with the classical criteria.
In the overall collective 39 patients were nodal negative, aged more
than 35 years and had pT1, ER positive and good to moderate differentiated
tumors. Of these patients 4 experienced a relapse. Combining information
from molecular profiling and classical criteria allowed to identify
more patients at very low risk (<10% relapse risk). Conclusions:
The developed multi quantitative RT-PCR assay is a powerful tool
for the identification of breast cancer patients at minimal risk
who could be spared of unnecessary adjuvant chemotherapy. Our results
give supplementary and complementary information with respect to
the St. Gallen criteria.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/735}
}
@ARTICLE{Vuga2009,
author = {Vuga, Louis J. and Ben-Yehudah, Ahmi and Kovkarova-Naumovski, Elizabetha
and Oriss, Timothy and Gibson, Kevin F. and Feghali-Bostwick, Carol
and Kaminski, Naftali},
title = {WNT5A Is a Regulator of Fibroblast Proliferation and Resistance to
Apoptosis},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2009},
volume = {41},
pages = {583--589},
number = {5},
month = nov,
abstract = {Usual interstitial pneumonia (UIP) is a specific histopathologic pattern
of interstitial lung fibrosis that may be idiopathic or secondary
to autoimmune diseases and environmental exposures. In this study,
we compared gene expression patterns in primary fibroblasts isolated
from lung tissues with UIP histology and fibroblasts isolated from
lung tissues with normal histology using expression microarrays.
We found that WNT5A was significantly increased in fibroblasts obtained
from UIP lung tissues compared with normal lung fibroblasts, an observation
verified by quantitative real-time RT-PCR and Western blot. Because
the role of WNT5A in UIP is unknown, we treated normal lung fibroblasts
or UIP lung fibroblasts with WNT5A, and found that WNT5A increased
proliferation as well as relative resistance to H2O2-induced apoptosis.
This effect was not mediated through the canonical WNT/{beta}-catenin
pathway, as WNT5A induced a decrease in {beta}-catenin levels in
the same cells. In addition, WNT5A induced increases in fibronectin
and {alpha}5-integrin in normal lung fibroblasts. Collectively, our
data suggest that WNT5A may play a role in fibroblast expansion and
survival characteristics of idiopathic pulmonary fibrosis and other
fibrotic interstitial lung diseases that exhibit UIP histological
patterns.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/41/5/583}
}
@ARTICLE{Vukkadapu2005,
author = {Vukkadapu, Sankaranand S. and Belli, Jenine M. and Ishii, Koji and
Jegga, Anil G. and Hutton, John J. and Aronow, Bruce J. and Katz,
Jonathan D.},
title = {Dynamic interaction between T cell-mediated {beta}-cell damage and
{beta}-cell repair in the run up to autoimmune diabetes of the NOD
mouse},
journal = {Physiol Genomics},
year = {2005},
volume = {21},
pages = {201--211},
number = {2},
month = apr,
abstract = {In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes,
the pathogenic destruction of the insulin-producing pancreatic {beta}-cells
is under the control of and influenced by distinct subsets of T lymphocytes.
To identify the critical genes expressed by autoimmune T cells, antigen
presenting cells, and pancreatic {beta}-cells during the evolution
of T1DM in the nonobese diabetic (NOD) mouse, and the genetically-altered
NOD mouse (BDC/N), we used functional genomics. Microarray analysis
revealed increased transcripts of genes encoding inflammatory cytokines,
particularly interleukin (IL)-17, and islet cell regenerating genes,
Reg3{alpha}, Reg3{beta}, and Reg3{gamma}. Our data indicate that
progression to insulitis was connected to marked changes in islet
antigen expression, {beta}-cell differentiation, and T cell activation
and signaling, all associated with tumor necrosis factor-{alpha}
and IL-6 expression. Overt diabetes saw a clear shift in cytokine,
chemokine, and T cell differentiation factor expression, consistent
with a focused Th1 response, as well as a significant upregulation
in genes associated with cellular adhesion, homing, and apoptosis.
Importantly, the temporal pattern of expression of key verified genes
suggested that T1DM develops in a relapsing/remitting as opposed
to a continuous fashion, with insulitis linked to hypoxia-regulated
gene control and diabetes with C/EBP and Nkx2 gene control.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/21/2/201}
}
@ARTICLE{Vyetrogon2007,
author = {Vyetrogon, Kateryna and Tebbji, Faiza and Olson, Douglas J. H. and
Ross, Andrew R. S. and Matton, Daniel P.},
title = {A comparative proteome and phosphoproteome analysis of differentially
regulated proteins during fertilization in the self-incompatible
species Solanum chacoense Bitt.},
journal = {Proteomics},
year = {2007},
volume = {7},
pages = {232--247},
number = {2},
abstract = {Abstract 10.1002/pmic.200600399.abs We have used 2-DE for a time-course
study of the changes in protein and phosphoprotein expression that
occur immediately after fertilization in Solanum chacoense. The phosphorylation
status of the detected proteins was determined with three methods:
in vivo labeling, immunodetection, and phosphoprotein-specific staining.
Using a pI range of 4–7, 262 phosphorylated proteins could be mapped
to the 619 proteins detected by Sypro Ruby staining, representing
42% of the total proteins. Among these phosphoproteins, antibodies
detected 184 proteins from which 78 were also detected with either
of the other two methods (42%). Pro-Q Diamond phosphoprotein stain
detected 111 proteins, of which 76 were also detected with either
of the other two methods (68%). The 32P in vivo labeling method detected
90 spots from which 78 were also detected with either of other two
methods (87%). On comparing before and after fertilization profiles,
38 proteins and phosphoproteins presented a reproducible change in
their accumulation profiles. Among these, 24 spots were selected
and analyzed by LC-MS/MS using a hybrid quadrupole-TOF (Q-TOF) instrument.
Peptide data were searched against publicly available protein and
EST databases, and the putative roles of the identified proteins
in early fertilization events are discussed.},
issn = {1615-9861},
keywords = {Embryogenesis, Fertilization, Phosphoproteome, Solanum chacoense,
Two-dimensional gel electrophoresis},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.200600399}
}
@ARTICLE{Vysotskaya2010,
author = {Vysotskaya, Lidia and Hedley, Peter E. and Sharipova, Guzel and Veselov,
Dmitry and Kudoyarova, Guzel and Morris, Jennifer and Jones, Hamlyn
G.},
title = {Effect of salinity on water relations of wild barley plants differing
in salt tolerance},
journal = {AoB Plants},
year = {2010},
volume = {2010},
pages = {plq006--},
number = {0},
month = jul,
abstract = {Background and aimsCertain lines of wild barley (Hordeum spontaneum)
are more tolerant of salinity than others. The physiological basis
of this difference is examined in a comparative study of a saline-tolerant
and saline-intolerant line that emphasizes plant water relations.
MethodologyEffects of salt-treatment (75 mM maximum) extending from
a few hours to 3 weeks were quantified in 8-day-old seedlings of
a saline-sensitive wild barley line ( T-1') and a less saline-sensitive
line ( 20-45'). Plants were grown in nutrient culture. Levels of
mRNA of the HtPIP2;4 aquaporin (AQP) gene were determined together
with a range of physiological responses including root hydraulic
conductivity, osmotic potential of root xylem sap, transpiration,
leaf relative water content, root water content, leaf water potential,
leaf sap osmolality, leaf length, leaf area and chlorophyll content.
Principal resultsSalt treatment inhibited transpiration and hydraulic
conductivity more in salt-tolerant 20-45' plants than in salt-sensitive
T-1'. In 20-45', the effect was paralleled by a fast (within a few
hours) and persistent (3 days) down-regulation of aquaporin. In salt-sensitive
T-1' plants, aquaporin down-regulation was delayed for up to 24 h.
Greater tolerance in 20-45' plants was characterized by less inhibition
of leaf area, root fresh weight, leaf water content and chlorophyll
concentration. Leaf water potentials were similar in both lines.
Conclusions(i) Decline in hydraulic conductivity in salt-treated
barley plants is important for stomatal closure, (ii) lowered transpiration
rate is beneficial for salt tolerance, at least at the seedling stage
and (iii) changes in AQP expression are implicated in the control
of whole plant hydraulic conductivity and the regulation of shoot
water relations.},
url = {http://aobpla.oxfordjournals.org/cgi/content/abstract/2010/0/plq006}
}
@ARTICLE{Varkonyi2011,
author = {Várkonyi, T. and Nagy, B. and Füle, T. and Tarca, A.L. and Karászi,
K. and Schönléber, J. and Hupuczi, P. and Mihalik, N. and Kovalszky,
I. and Rigó Jr., J. and Meiri, H. and Papp, Z. and Romero, R. and
Than, N.G.},
title = {Microarray Profiling Reveals That Placental Transcriptomes of Early-onset
HELLP Syndrome and Preeclampsia Are Similar},
journal = {Placenta},
year = {2011},
volume = {32},
pages = {S21--S29},
number = {Supplement 1},
month = feb,
abstract = {Background The involvement of the placenta in the pathogenesis of
preeclampsia and HELLP syndrome is well established, and placental
lesions are also similar in these two syndromes. Here we aimed to
examine the placental transcriptome and to identify candidate biomarkers
in early-onset preeclampsia and HELLP syndrome.Methods Placental
specimens were obtained at C-sections from women with early-onset
preeclampsia and HELLP syndrome, and from controls who delivered
preterm or at term. After histopathological examination, fresh-frozen
placental specimens were used for microarray profiling and validation
by qRT-PCR. Differential expression was analysed using log-linear
models while adjusting for gestational age. Gene ontology and pathway
analyses were used to interpret gene expression changes. Tissue microarrays
were constructed from paraffin-embedded placental specimens and immunostained.Results
Placental gene expression was gestational age-dependent among preterm
and term controls. Out of the 350 differentially expressed genes
in preeclampsia and 554 genes in HELLP syndrome, 224 genes (including
LEP, CGB, LHB, INHA, SIGLEC6, PAPPA2, TREM1, and FLT1) changed in
the same direction (elevated or reduced) in both syndromes. Many
of these encode proteins that have been implicated as biomarkers
for preeclampsia. Enrichment analyses revealed similar biological
processes, cellular compartments and biological pathways enriched
in early-onset preeclampsia and HELLP syndrome; however, some processes
and pathways (e.g., cytokine-cytokine receptor interaction) were
over-represented only in HELLP syndrome.Conclusion High-throughput
transcriptional and tissue microarray expression profiling revealed
that placental transcriptomes of early-onset preeclampsia and HELLP
syndrome largely overlap, underlying a potential common cause and
pathophysiologic processes in these syndromes. However, gene expression
changes may also suggest a more severe placental pathology and pronounced
inflammatory response in HELLP syndrome than in preeclampsia.},
booktitle = {The PREGENESYS Project: challenges for early detection of preeclampsia
by multiple markers and their use to evaluate preventive and management
agents by in-vitro models},
issn = {0143-4004},
keywords = {Differential expression, High-dimensional biology, Syncytiotrophoblast,
Systemic inflammation, Virtual microscopy},
url = {http://www.sciencedirect.com/science/article/pii/S0143400410001736}
}
@ARTICLE{VAªncio2011,
author = {Vêncio, Eneida F. and Pascal, Laura E. and Page, Laura S. and Denyer,
Gareth and Wang, Amy J. and Ruohola-Baker, Hannele and Zhang, Shile
and Wang, Kai and Galas, David J. and Liu, Alvin Y.},
title = {Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured
prostate stromal fibromuscular cells},
journal = {Journal of Cellular Physiology},
year = {2011},
volume = {226},
pages = {1479--1488},
number = {6},
abstract = {Abstract The prostate stromal mesenchyme controls organ-specific development.
In cancer, the stromal compartment shows altered gene expression
compared to non-cancer. The lineage relationship between cancer-associated
stromal cells and normal tissue stromal cells is not known. Nor is
the cause underlying the expression difference. Previously, the embryonal
carcinoma (EC) cell line, NCCIT, was used by us to study the stromal
induction property. In the current study, stromal cells from non-cancer
(NP) and cancer (CP) were isolated from tissue specimens and co-cultured
with NCCIT cells in a trans-well format to preclude heterotypic cell
contact. After 3 days, the stromal cells were analyzed by gene arrays
for microRNA (miRNA) and mRNA expression. In co-culture, NCCIT cells
were found to alter the miRNA and mRNA expression of NP stromal cells
to one like that of CP stromal cells. In contrast, NCCIT had no significant
effect on the gene expression of CP stromal cells. We conclude that
the gene expression changes in stromal cells can be induced by diffusible
factors synthesized by EC cells, and suggest that cancer-associated
stromal cells represent a more primitive or less differentiated stromal
cell type. J. Cell. Physiol. 226: 1479–1488, 2011. © 2010 Wiley-Liss,
Inc.},
doi = {10.1002/jcp.22464},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22464}
}
@ARTICLE{VAµsa2011,
author = {Võsa, Urmo and Vooder, Tõnu and Kolde, Raivo and Fischer, Krista
and Välk, Kristjan and Tõnisson, Neeme and Roosipuu, Retlav and
Vilo, Jaak and Metspalu, Andres and Annilo, Tarmo},
title = {Identification of miR-374a as a prognostic marker for survival in
patients with early-stage nonsmall cell lung cancer},
journal = {Genes, Chromosomes and Cancer},
year = {2011},
volume = {50},
pages = {812--822},
number = {10},
abstract = {Lung cancer is one of the deadliest types of cancer proven by the
poor survival and high relapse rates after surgery. Recently discovered
microRNAs (miRNAs), small noncoding RNA molecules, play a crucial
role in modulating gene expression networks and are directly involved
in the progression of a number of human cancers. In this study, we
analyzed the expression profile of 858 miRNAs in 38 Estonian nonsmall
cell lung cancer (NSCLC) samples (Stage I and II) and 27 adjacent
nontumorous tissue samples using Illumina miRNA arrays. We found
that 39 miRNAs were up-regulated and 33 down-regulated significantly
in tumors compared with normal lung tissue. We observed aberrant
expression of several well-characterized tumorigenesis-related miRNAs,
as well as a number of miRNAs whose function is currently unknown.
We show that low expression of miR-374a in early-stage NSCLC is associated
with poor patient survival. The combinatorial effect of the up- and
down-regulated miRNAs is predicted to most significantly affect pathways
associated with cell migration, differentiation and growth, and several
signaling pathways that contribute to tumorigenesis. In conclusion,
our results demonstrate that expression of miR-374a at early stages
of NSCLC progression can serve as a prognostic marker for patient
risk stratification and may be a promising therapeutic target for
the treatment of lung cancer. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/gcc.20902},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20902}
}
@ARTICLE{Waard2010,
author = {de Waard, Monique C. and van Haperen, Rien and Soullié, Thomas and
Tempel, Dennie and de Crom, Rini and Duncker, Dirk J.},
title = {Beneficial effects of exercise training after myocardial infarction
require full eNOS expression},
journal = {J Mol Cell Cardiol},
year = {2010},
volume = {48},
pages = {1041--1049},
number = {6},
month = jun,
abstract = {Exercise training attenuates left ventricular (LV) dysfunction after
myocardial infarction (MI). It could be speculated that these effects
of exercise are mediated by increased endothelial NO synthase (eNOS)
activity. In the present study we tested the hypothesis that eNOS
plays a critical role in the exercise-induced amelioration of LV
dysfunction after MI. MI or sham was induced in eNOS−/−, eNOS+/−
and eNOS+/+ mice. After 8weeks of voluntary wheel running (∼7km/day
in all groups) or sedentary housing, global cardiac function was
determined in vivo and (immuno)histochemistry was performed to assess
cardiomyocyte size, fibrosis, capillary density and apoptosis in
remote myocardium. At baseline eNOS−/− mice had higher mean aortic
pressure compared to eNOS+/− and eNOS+/+ mice, but had normal global
cardiac function. MI resulted in marked LV remodeling, including
cardiomyocyte hypertrophy and a reduction in capillary density, increased
fibrosis and apoptosis, as well as LV systolic and diastolic dysfunction
to the same extent in all genotypes. In eNOS+/+ MI mice exercise
abolished fibrosis and apoptosis in the remote myocardium, attenuated
LV systolic dysfunction and ameliorated pulmonary congestion. These
beneficial effects were lost in eNOS+/− and eNOS−/− mice, while
LV systolic dysfunction and pulmonary congestion in eNOS+/− mice
were exacerbated by exercise. In conclusion, the beneficial effects
of exercise after MI on LV remodeling and dysfunction depend critically
on endogenous eNOS. The observation that the lack of one eNOS allele
is sufficient to negate all beneficial effects of exercise, strongly
suggests that exercise depends on full eNOS expression.},
issn = {0022-2828},
keywords = {Exercise training, Myocardial infarction, eNOS, Cardiac function,
Mice, Cardiac remodeling},
publisher = {Academic Press.},
refid = {S0022-2828(10)00040-4},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0022282810000404?showall=true}
}
@ARTICLE{Wabitsch2007,
author = {Wabitsch, M. and Lahr, G. and Van de Bunt, M. and Marchant, C. and
Lindner, M. and Von Puttkamer, J. and Fenneberg, A. and Debatin,
K. M. and Klein, R. and Ellard, S. and Clark, A. and Gloyn, A. L.},
title = {Heterogeneity in disease severity in a family with a novel G68V GCK
activating mutation causing persistent hyperinsulinaemic hypoglycaemia
of infancy},
journal = {Diabetic Medicine},
year = {2007},
volume = {24},
pages = {1393--1399},
number = {12},
abstract = {Abstract Background/aim Glucokinase (GCK)-activating mutations cause
persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI). GCK-PHHI
patients have regulated insulin secretion and can usually be treated
with diazoxide. The six reported cases suggest that the severity
of the mutation predicts the clinical phenotype. The aim of this
study was to relate genotype to phenotype [clinical phenotype, glucose-stimulated
insulin release (GSIR) and GCK functional analysis] in a large pedigree
with eight affected individuals. Methods The genes encoding B-cell
GCK and the KATP channel subunits (ABCC8 and KCNJ11) were sequenced
to identify mutations for functional analysis. Genetic variants influencing
B-cell function were genotyped in affected individuals. Islet secretory
capacity was determined by oral glucose tolerance test ResultsÂ
A novel GCK mutation (G68V) co-segregating with hypoglycaemia was
identified in eight family members. Kinetic analysis revealed that
G68V-GCK activity is ~16 times more than wild-type-GCK with an increased
affinity for glucose [concentration at half maximal activation (S0.5)
1.94 ± 0.16 vs. 7.43 ± 0.12, mutant vs. wild type, mean ± sem].
Mathematical modelling predicted a threshold for GSIR of 1.9Â mmol/l
in the mutant. Oral glucose tolerance tests showed regulated insulin
secretion. The severity of hypoglycaemia and related symptoms in
affected subjects were heterogeneous. Clinical presentations were
asymptomatic (n = 1), extreme hunger (n = 3), seizures (n = 2)
and loss of consciousness (n = 2); 7/8 were managed with diet but
the proband was treated with diazoxide and octreotide. Phenotypic
modification by a second mutation in the KATP channel genes (ABCC8,
KCNJ11) or by common genetic variants in KCNJ11, GCK and TCF7L2 was
excluded. Conclusion The novel activating GCK mutation G68V is
associated with variable phenotypic severity, supporting modification
of GSIR by genetic and/or environmental factors.},
issn = {1464-5491},
keywords = {diazoxide, genetics, glucokinase, octreotide, persistent hyperinsulinaemic
hypoglycaemia of infancy},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1464-5491.2007.02285.x}
}
@ARTICLE{Wachtel2004,
author = {Wachtel, Marco and Dettling, Marcel and Koscielniak, Eva and Stegmaier,
Sabine and Treuner, Jorn and Simon-Klingenstein, Katja and Buhlmann,
Peter and Niggli, Felix K. and Schafer, Beat W.},
title = {Gene Expression Signatures Identify Rhabdomyosarcoma Subtypes and
Detect a Novel t(2;2)(q35;p23) Translocation Fusing PAX3 to NCOA1},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {5539--5545},
number = {16},
month = aug,
abstract = {Rhabdomyosarcoma is a pediatric tumor type, which is classified based
on histological criteria into two major subgroups, namely embryonal
rhabdomyosarcoma and alveolar rhabdomyosarcoma. The majority, but
not all, alveolar rhabdomyosarcoma carry the specific PAX3(7)/FKHR-translocation,
whereas there is no consistent genetic abnormality recognized in
embryonal rhabdomyosarcoma. To gain additional insight into the genetic
characteristics of these subtypes, we used oligonucleotide microarrays
to measure the expression profiles of a group of 29 rhabdomyosarcoma
biopsy samples (15 embryonal rhabdomyosarcoma, and 10 translocation-positive
and 4 translocation-negative alveolar rhabdomyosarcoma). Hierarchical
clustering revealed expression signatures clearly discriminating
all three of the subgroups. Differentially expressed genes included
several tyrosine kinases and G protein-coupled receptors, which might
be amenable to pharmacological intervention. In addition, the alveolar
rhabdomyosarcoma signature was used to classify an additional alveolar
rhabdomyosarcoma case lacking any known PAX3 or PAX7 fusion as belonging
to the translocation-positive group, leading to the identification
of a novel translocation t(2;2)(q35;p23), which generates a fusion
protein composed of PAX3 and the nuclear receptor coactivator NCOA1,
having similar transactivation properties as PAX3/FKHR. These experiments
demonstrate for the first time that gene expression profiling is
capable of identifying novel chromosomal translocations.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/16/5539}
}
@ARTICLE{Waddell2010,
author = {Waddell, Nic and Cocciardi, Sibylle and Johnson, Julie and Healey,
Sue and Marsh, Anna and Riley, Joan and Silva, Leonard da and Vargas,
Ana Cristina and Reid, Lynne and Simpson, Peter T and Lakhani, Sunil
R and Chenevix-Trench, Georgia},
title = {Gene expression profiling of formalin-fixed, paraffin-embedded familial
breast tumours using the whole genome-DASL assay},
journal = {J. Pathol.},
year = {2010},
volume = {221},
pages = {452--461},
number = {4},
abstract = {Abstract 10.1002/path.2728.abs Tissue sample acquisition is a limiting
step in many studies. There are many thousands of formalin-fixed,
paraffin-embedded archival blocks collected around the world, but
in contrast relatively few fresh frozen samples in tumour banks.
Once samples are fixed in formalin, the RNA is degraded and traditional
methods for gene expression profiling are not suitable. In this study,
we have evaluated the ability of the whole genome DASL (cDNA-mediated
Annealing, Selection, extension, and Ligation) assay from Illumina
to perform transcriptomic analysis of archived breast tumour tissue
in formalin-fixed, paraffin-embedded (FFPE) blocks. We profiled 76
familial breast tumours from cases carrying a BRCA1, BRCA2 or ATM
mutation, or from non-BRCA1/2 families. We found that replicate samples
correlated well with each other (r2 = 0.9–0.98). In 12/15 cases,
the matched formalin-fixed and frozen samples predicted the same
tumour molecular subtypes with confidence. These results demonstrate
that the whole genome DASL assay is a valuable tool to profile degraded
RNA from archival FFPE material. This assay will enable transcriptomic
analysis of a large number of archival samples that are stored in
pathology archives around the globe and consequently will have the
potential to improve our understanding and characterization of many
diseases. Copyright © 2010 Pathological Society of Great Britain
and Ireland. Published by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {BRCA1 and BRCA2, ATM, molecular subtypes, familial breast cancer,
gene expression, formalin-fixed, paraffin-embedded tissue, whole
genome DASL},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2728}
}
@ARTICLE{Waddell2006,
author = {Waddell, Nic and Jonnalagadda, Jyoti and Marsh, Anna and Grist, Scott
and Jenkins, Mark and Hobson, Karen and Taylor, Malcolm and Lindeman,
Geoff J. and Tavtigian, Sean V. and Suthers, Graeme and Goldgar,
David and Oefner, Peter J. and Taylor, Darrin and Grimmond, Sean
and Khanna, Kum Kum and Chenevix-Trench, Georgia},
title = {Characterization of the breast cancer associated ATM 7271T>G (V2424G)
mutation by gene expression profiling},
journal = {Genes Chromosom. Cancer},
year = {2006},
volume = {45},
pages = {1169--1181},
number = {12},
abstract = {Abstract 10.1002/gcc.20381.abs Mutations in ATM are responsible for
the autosomal recessive disorder ataxia telangiectasia. Heterozygous
mutations in ATM have been associated with an elevated risk of breast
cancer. We previously reported one breast cancer family in which
ATM 7271T>G (V2424G) segregated with disease, and apparently acted
in a dominant negative manner. We now report the screening of 782
multiple-case breast cancer families that identified two additional
index cases with ATM 7271T>G. Phylogenetic sequence analysis showed
that V2424 is a highly conserved residue, and that the 2424G variant
is likely to interfere with function. To elucidate the consequences
of this mutation, we expression profiled wild-type, heterozygous,
and homozygous lymphoblastoid cell lines (LCLs) from Scottish and
Australian families using an oligonucleotide microarray. Cluster
analysis revealed 77 genes that were differentially expressed in
homozygous and heterozygous V2424G cells (compared to wild-type)
and 11 genes differentially expressed in the homozygous cells. We
also evaluated the profiles of LCLs after exposure to ionizing radiation
(IR) and identified 77 genes that were differentially expressed in
wild-type cells, but not in homozygous or heterozygous V2424G cells.
We validated the expression differences by RT-PCR in additional heterozygous
V2424G LCLs from another breast cancer family. We found no consistent
cytotoxicity or abrogation of ATM kinase activity after IR in seven
heterozygous V2424G LCLs, compared to wild-type LCLs, but did find
an increase in the number of chromosomal aberrations. These data
suggest that the V2424G missense mutation acts largely as a dominant
negative in terms of the associated expression profiles. © 2006
Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20381}
}
@ARTICLE{Waddell2008,
author = {Waddell, Simon and Laing, Ken and Senner, Claire and Butcher, Philip},
title = {Microarray analysis of defined Mycobacterium tuberculosis populations
using RNA amplification strategies},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {94},
number = {1},
abstract = {BACKGROUND:The amplification of bacterial RNA is required if complex
host-pathogen interactions are to be studied where the recovery of
bacterial RNA is limited. Here, using a whole genome Mycobacterium
tuberculosis microarray to measure cross-genome representation of
amplified mRNA populations, we have investigated two approaches to
RNA amplification using different priming strategies. The first using
oligo-dT primers after polyadenylation of the bacterial RNA, the
second using a set of mycobacterial amplification-directed primers
both linked to T7 polymerase in vitro run off transcription.RESULTS:The
reproducibility, sensitivity, and the representational bias introduced
by these amplification systems were examined by contrasting expression
profiles of the amplified products from inputs of 500, 50 and 5 ng
total M. tuberculosis RNA with unamplified RNA from the same source.
In addition, as a direct measure of the effectiveness of bacterial
amplification for identifying biologically relevant changes in gene
expression, a model M. tuberculosis system of microaerophilic growth
and non-replicating persistence was used to assess the capability
of amplified RNA microarray comparisons. Mycobacterial RNA was reproducibly
amplified using both methods from as little as 5 ng total RNA (~equivalent
to 2 × 105 bacilli). Differential gene expression patterns observed
with unamplified RNA in the switch from aerobic to microaerophilic
growth were also reflected in the amplified expression profiles using
both methods.CONCLUSION:Here we describe two reproducible methods
of bacterial RNA amplification that will allow previously intractable
host-pathogen interactions during bacterial infection to be explored
at the whole genome level by RNA profiling.},
doi = {10.1186/1471-2164-9-94},
issn = {1471-2164},
pubmedid = {18298834},
url = {http://www.biomedcentral.com/1471-2164/9/94}
}
@ARTICLE{Wade2010,
author = {Wade, Hilary E. and Kobayashi, Sakiko and Eaton, Matthew L. and Jansen,
Michelle S. and Lobenhofer, Edward K. and Lupien, Mathieu and Geistlinger,
Timothy R. and Zhu, Wencheng and Nevins, Joseph R. and Brown, Myles
and Otteson, Deborah C. and McDonnell, Donald P.},
title = {Multimodal Regulation of E2F1 Gene Expression by Progestins},
journal = {Mol. Cell. Biol.},
year = {2010},
volume = {30},
pages = {1866--1877},
number = {8},
month = apr,
abstract = {An analysis of mRNA expression in T47D breast cancer cells treated
with the synthetic progestin R5020 revealed a subset of progesterone
receptor (PR) target genes that are enriched for E2F binding sites.
Following up on this observation, we determined that PR-B acts in
both direct and indirect manners to positively upregulate E2F1 expression
in T47D cells. The direct effects of PR on E2F1 expression were confirmed
by chromatin immunoprecipitation (ChIP) analysis, which indicated
that the agonist-bound receptor was recruited to several enhancer
elements proximal to the E2F1 transcript. However, we also noted
that cycloheximide partially inhibits R5020 induction of E2F1 expression,
indicating that the ligand-dependent actions of PR on this gene may
involve additional indirect regulatory pathways. In support of this
hypothesis, we demonstrated that treatment with R5020 significantly
increases both hyperphosphorylation of Rb and recruitment of E2F1
to its own promoter, thus activating a positive feedback loop that
further amplifies its transcription. Furthermore, we established
that PR-mediated induction of Kruppel-like factor 15 (KLF15), which
can bind to GC-rich DNA within the E2F1 promoter, is required for
maximal induction of E2F1 expression by progestins. Taken together,
these results suggest a new paradigm for multimodal regulation of
target gene expression by PR.},
url = {http://mcb.asm.org/cgi/content/abstract/30/8/1866}
}
@ARTICLE{Wade2006,
author = {Wade, Kelly C. and Guttentag, Susan H. and Gonzales, Linda W. and
Maschhoff, Kathryn L. and Gonzales, John and Kolla, Venkatadri and
Singhal, Sunil and Ballard, Philip L.},
title = {Gene Induction during Differentiation of Human Pulmonary Type II
Cells In Vitro},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2006},
volume = {34},
pages = {727--737},
number = {6},
month = jun,
abstract = {Mature alveolar type II cells that produce pulmonary surfactant are
essential for adaptation to extrauterine life. We profiled gene expression
in human fetal lung epithelial cells cultured in serum-free medium
containing dexamethasone and cyclic AMP, a treatment that induces
differentiation of type II cells. Microarray analysis identified
388 genes that were induced > 1.5-fold by 72 h of hormone treatment.
Induced genes represented all categories of molecular function and
subcellular location, with increased frequency in the categories
of ionic channel, cell adhesion, surface film, lysosome, extracellular
matrix, and basement membrane. In time-course experiments, self-organizing
map analysis identified a cluster of 17 genes that were slowly but
highly induced (5- to [~] 190-fold) and represented four functional
categories: surfactant-related (SFTPC, SFTPA, PGC, SFTPB, LAMP3,
LPL), regulatory (WIF2, IGF2, IL1RL1, NR4A2, HIF3A), metabolic (MAOA,
ADH1B, SEPP1), and transport (SCNN1A, CLDN18, AQP4). Induction of
both mRNA and protein for these genes, which included nine newly
identified regulated genes, was confirmed, and cellular localization
was determined in both fetal and postnatal tissue. Induction of lysosomal-associated
membrane protein 3 required both hormones, and expression was localized
to limiting membranes of lamellar bodies. Hormone-induced differentiation
of human type II cells is associated with genome-wide increased expression
of genes with diverse functions.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/34/6/727}
}
@ARTICLE{Wade2008,
author = {Wade, Michael G. and Kawata, Alice and Williams, Andrew and Yauk,
Carole},
title = {Methoxyacetic Acid-Induced Spermatocyte Death Is Associated with
Histone Hyperacetylation in Rats},
journal = {Biol Reprod},
year = {2008},
volume = {78},
pages = {822--831},
number = {5},
month = may,
abstract = {We used high-density microarrays to evaluate the possible mechanisms
by which 2-methoxyacetic acid (MAA) disrupts spermatogenesis. Levels
of mRNA transcripts were determined in total RNA isolated from testes
of MAA-treated (650 mg/kg i.p.) or concurrent control rats killed
4, 8, 12, or 24 h postexposure (PE). Germ cell death was examined
in testis sections using in situ staining for DNA fragmentation.
MAA treatment caused increased death of pachytene spermatocytes starting
8 h PE and increasing dramatically at 12 and 24 h PE. Microarray
results indicated that at 4 h PE the transcript levels of seven different
genes were significantly overrepresented in the testes of MAA-exposed
animals. One gene (histone H1 zero [H1f0]) was significantly overrepresented
in MAA-treated samples at 4, 8, and 12 h PE. Because expression of
this gene has been associated with increased acetylation of core
histones, we examined MAA-induced changes in the acetylation of histones
H4 (HISTH4) and H3 (HISTH3) in testis nuclear protein. Western blots
of acid-extracted testis nuclei indicated that the levels of tetraacetyl
histone H4 (4acHIST1H4) and of diacetyl histone H3 (2acHIST1H3) were
elevated by MAA treatment at 4, 8, and 12 h PE. Using the same antibodies,
4acHIST1H4 and 2acHIST1H3 were localized primarily to elongating
spermatids in testis sections from control animals. At 4 h PE, staining
for either histone modification was dramatically increased in spermatogonia
and all primary spermatocyte populations except for dividing spermatocytes.
MAA treatment of testis nuclear protein extracts from unexposed animals
caused both a significant increase in histone acetyltransferase activity
and a significant inhibition of histone deacetylase activity, suggesting
that increased core histone acetylation results from a combination
of these complementary modes of action. Our results indicate that
exposure to MAA causes increased acetylation of core histones in
several testis germ cell populations, including those in prophase
of meiosis, a large proportion of which die rapidly following this
treatment.},
url = {http://www.biolreprod.org/cgi/content/abstract/78/5/822}
}
@ARTICLE{Wade2009,
author = {Wade, Terence E. and Mathur, Abhishek and Lu, Debao and Swartz-Basile,
Deborah A. and Pitt, Henry A. and Zyromski, Nicholas J.},
title = {Adiponectin Receptor-1 Expression Is Decreased in the Pancreas of
Obese Mice},
journal = {Journal of Surgical Research},
year = {2009},
volume = {154},
pages = {78--84},
number = {1},
month = jun,
abstract = {Background Obesity is epidemic in the 21st century and has been shown
to be a risk factor for developing severe acute pancreatitis. Adipose
tissue produces small molecules called adipokines, which are important
in modulating metabolism and inflammation. The anti-inflammatory
adipokine adiponectin is decreased in obesity and inversely mirrors
the severity of pancreatitis in a murine experimental model. Adiponectin
acts through two receptors, AdipoR1 and AdipoR2; no data are currently
available regarding adiponection receptor expression in the obese
murine pancreas.Materials and methods Immunohistochemical and reverse
transcription-polymerase chain reaction analysis were undertaken
to determine expression of adiponectin receptors AdipoR1 and AdipoR2
in the pancreas and liver of lean (C57BL/6J) and congenitally obese
(LepOb and LepDb) mice.Results Immunohistochemistry confirmed expression
of both AdipoR1 and AdipoR2 in the pancreas of all three murine strains.
Staining was positive in acinar cells and to a lesser extent in islet
cells. Pancreatic gene expression of AdipoR2 was similar among lean
and obese mice. AdipoR1 gene expression, however, was significantly
(P < 0.001) decreased in the pancreas of both LepOb and LepDb mice
compared to wild-type lean animals. Gene expression of both AdipoR1
and AdipoR2 was significantly less in the liver of obese (LepOb and
LepDb) mice compared to wild-type lean animals (P < 0.001).Conclusions
These data show for the first time that the adiponectin receptors
AdipoR1 and AdipoR2 are expressed in the obese murine pancreas. The
paucity of AdipoR1 receptors may be important when considering the
role played by adipokines in the genesis of severe pancreatitis in
obesity.},
issn = {0022-4804},
keywords = {adiponectin, adiponectin receptors, pancreatitis, obesity},
url = {http://www.sciencedirect.com/science/article/B6WM6-4SN985F-2/2/33cc02b3cba8e7d8302ee0d68c09a34d}
}
@ARTICLE{Wadley2007,
author = {Wadley, G. D. and McConell, G. K.},
title = {Effect of nitric oxide synthase inhibition on mitochondrial biogenesis
in rat skeletal muscle},
journal = {J Appl Physiol},
year = {2007},
volume = {102},
pages = {314--320},
number = {1},
month = jan,
abstract = {The purpose of this study was to determine whether nitric oxide synthase
(NOS) inhibition decreased basal and exercise-induced skeletal muscle
mitochondrial biogenesis. Male Sprague-Dawley rats were assigned
to one of four treatment groups: NOS inhibitor NG-nitro-L-arginine
methyl ester (L-NAME, ingested for 2 days in drinking water, 1 mg/ml)
followed by acute exercise, no L-NAME ingestion and acute exercise,
rest plus L-NAME, and rest without L-NAME. The exercised rats ran
on a treadmill for 53 {+/-} 2 min and were then killed 4 h later.
NOS inhibition significantly (P < 0.05; main effect) decreased basal
peroxisome proliferator-activated receptor-{gamma} coactivator 1[beta]
(PGC-1[beta]) mRNA levels and tended (P = 0.08) to decrease mtTFA
mRNA levels in the soleus, but not the extensor digitorum longus
(EDL) muscle. This coincided with significantly reduced basal levels
of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and
COX enzyme activity following NOS inhibition in the soleus, but not
the EDL muscle. NOS inhibition had no effect on citrate synthase
or [beta]-hydroxyacyl CoA dehydrogenase activity, or cytochrome c
protein abundance in the soleus or EDL. NOS inhibition did not reduce
the exercise-induced increase in peroxisome proliferator-activated
receptor-{gamma} coactivator 1{alpha} (PGC-1{alpha}) mRNA in the
soleus or EDL. In conclusion, inhibition of NOS appears to decrease
some aspects of the mitochondrial respiratory chain in the soleus
under basal conditions, but does not attenuate exercise-induced mitochondrial
biogenesis in the soleus or in the EDL.},
url = {http://jap.physiology.org/cgi/content/abstract/102/1/314}
}
@ARTICLE{Wadman2009,
author = {Wadman, Mayken and de Vries, Ronald and Kalkhove, Stefanie and Veldink,
Gerrit and Vliegenthart, Johannes},
title = {Characterization of oxylipins and dioxygenase genes in the asexual
fungus Aspergillus niger},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {59},
number = {1},
abstract = {BACKGROUND:Aspergillus niger is an ascomycetous fungus that is known
to reproduce through asexual spores, only. Interestingly, recent
genome analysis of A. niger has revealed the presence of a full complement
of functional genes related to sexual reproduction [1]. An example
of such genes are the dioxygenase genes which in Aspergillus nidulans,
have been shown to be connected to oxylipin production and regulation
of both sexual and asexual sporulation [2-4]. Nevertheless,
the presence of sex related genes alone does not confirm sexual sporulation
in A. niger.RESULTS:The current study shows experimentally that A.
niger produces the oxylipins 8,11-dihydroxy octadecadienoic acid
(8,11-diHOD), 5,8-dihydroxy octadecadienoic acid (5,8-diHOD), lactonized
5,8-diHOD, 8-hydroxy octadecadienoic acid (8-HOD), 10-hydroxy octadecadienoic
acid (10-HOD), small amounts of 8-hydroxy octadecamonoenoic acid
(8-HOM), 9-hydroxy octadecadienoic acid (9-HOD) and 13-hydroxy octadecadienoic
acid (13-HOD). Importantly, this study shows that the A. niger genome
contains three putative dioxygenase genes, ppoA, ppoC and ppoD. Expression
analysis confirmed that all three genes are indeed expressed under
the conditions tested.CONCLUSION:A. niger produces the same oxylipins
and has similar dioxygenase genes as A. nidulans. Their presence
could point towards the existence of sexual reproduction in A. niger
or a broader role for the gene products in physiology, than just
sexual development.},
doi = {10.1186/1471-2180-9-59},
issn = {1471-2180},
pubmedid = {19309517},
url = {http://www.biomedcentral.com/1471-2180/9/59}
}
@ARTICLE{Wageningen2010,
author = {van Wageningen, Sake and Kemmeren, Patrick and Lijnzaad, Philip and
Margaritis, Thanasis and Benschop, Joris J. and de Castro, Inês J.
and van Leenen, Dik and Groot Koerkamp, Marian J.A. and Ko, Cheuk
W. and Miles, Antony J. and Brabers, Nathalie and Brok, Mariel O.
and Lenstra, Tineke L. and Fiedler, Dorothea and Fokkens, Like and
Aldecoa, Rodrigo and Apweiler, Eva and Taliadouros, Virginia and
Sameith, Katrin and van de Pasch, Loes A.L. and van Hooff, Sander
R. and Bakker, Linda V. and Krogan, Nevan J. and Snel, Berend and
Holstege, Frank C.P.},
title = {Functional Overlap and Regulatory Links Shape Genetic Interactions
between Signaling Pathways},
journal = {Cell},
year = {2010},
volume = {143},
pages = {991--1004},
number = {6},
month = dec,
abstract = {Summary To understand relationships between phosphorylation-based
signaling pathways, we analyzed 150 deletion mutants of protein kinases
and phosphatases in S. cerevisiae using DNA microarrays. Downstream
changes in gene expression were treated as a phenotypic readout.
Double mutants with synthetic genetic interactions were included
to investigate genetic buffering relationships such as redundancy.
Three types of genetic buffering relationships are identified: mixed
epistasis, complete redundancy, and quantitative redundancy. In mixed
epistasis, the most common buffering relationship, different gene
sets respond in different epistatic ways. Mixed epistasis arises
from pairs of regulators that have only partial overlap in function
and that are coupled by additional regulatory links such as repression
of one by the other. Such regulatory modules confer the ability to
control different combinations of processes depending on condition
or context. These properties likely contribute to the evolutionary
maintenance of paralogs and indicate a way in which signaling pathways
connect for multiprocess control.},
issn = {0092-8674},
keywords = {CELLBIO, SIGNALING},
url = {http://www.sciencedirect.com/science/article/pii/S0092867410013012}
}
@ARTICLE{Wagner2007,
author = {Wagner, Florian and Radelof, Uwe},
title = {Performance of different small sample RNA amplification techniques
for hybridization on Affymetrix GeneChips},
journal = {Journal of Biotechnology},
year = {2007},
volume = {129},
pages = {628--634},
number = {4},
month = may,
abstract = {A key issue in RNA amplification techniques is the preservation of
original transcript abundance, however popular high-grade RNA amplification
methods lack sufficient validation regarding the potential bias of
gene expression profiles. This study evaluated a double-round T7-based
and a PCR-based amplification protocol, using the Affymetrix GeneChip
platform. Both small sample methods performed excellently in terms
of yield and reproducibility (r > 0.99), and also the within-method
concordance with respect to differential gene expression was as high
as with standard single-round T7-based amplification. However, when
comparing the overlap of all differentially expressed genes between
standard and small sample methods, this was only moderate for the
double-round T7 (48.7-55.0%) as well as for the PCR-based amplification
protocol (51.9-58.0%). In contrast, the concordance for the top 100
genes with highest fold changes was significantly higher, indicating
that both small sample methods generate reliable results when focusing
on strongly regulated genes.},
issn = {0168-1656},
keywords = {DNA microarrays, RNA amplification techniques, Methodology, Evaluation,
Concordance},
url = {http://www.sciencedirect.com/science/article/B6T3C-4N4J2VP-7/2/9ceb9f062b2d59502f07cba33d83e9a9}
}
@ARTICLE{Wagner2007a,
author = {Wagner, Tracey H. and Drewry, Anne M. and MacMillan, Sandra and Dunne,
W. Michael and Chang, Katherine C. and Karl, Irene E. and Hotchkiss,
Richard S. and Cobb, J. Perren},
title = {Surviving sepsis: bcl-2 overexpression modulates splenocyte transcriptional
responses in vivo},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {292},
pages = {R1751--1759},
number = {4},
month = apr,
abstract = {We hypothesized that spleen microarray gene expression profiles analyzed
with contemporary pathway analysis software would provide molecular
pathways of interest and target genes that might help explain the
effect of bcl-2 on improving survival during sepsis. Two mouse models
of sepsis, cecal ligation and puncture and tracheal instillation
of Pseudomonas aeruginosa, were tested in both wild-type mice and
mice that overexpress bcl-2. Whole spleens were obtained 6 h after
septic injury. DNA microarray transcriptional profiles were obtained
using the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity
Pathway Analysis software was used to construct hypothetical transcriptional
networks that changed in response to sepsis and expression of the
bcl-2 transgene. A conservative approach was used wherein only changes
induced by both abdominal and pulmonary sepsis were studied. At 6
h, sepsis induced alterations in the abundance of hundreds of spleen
genes, including a number of proinflammatory mediators (e.g., interleukin-6).
These sepsis-induced alterations were blocked by expression of the
bcl-2 transgene. Network analysis implicated a number of bcl-2-related
apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and
mcl-1. Sepsis in bcl-2 transgenic animals resulted in alteration
of RNA abundance for only a single gene, ceacam1. These findings
are consistent with sepsis-induced alterations in the balance of
pro- and anti-apoptotic transcriptional networks. In addition, our
data suggest that the ability of bcl-2 overexpression to improve
survival in sepsis in this model is related in part to prevention
of sepsis-induced alterations in spleen transcriptional responses.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/292/4/R1751}
}
@ARTICLE{Wagner2004,
author = {Wagner, Victoria E. and Gillis, Richard J. and Iglewski, Barbara
H.},
title = {Transcriptome analysis of quorum-sensing regulation and virulence
factor expression in Pseudomonas aeruginosa},
journal = {Vaccine},
year = {2004},
volume = {22},
pages = {S15--S20},
number = {Supplement 1},
month = dec,
abstract = {The opportunistic pathogen Pseudomonas aeruginosa possesses two well-studied
quorum-sensing (QS) systems (las and rhl) that are important in the
production of virulence factors, antibiotic sensitivity, and biofilm
development. High-density oligonucleotide microarrays were used to
further characterize the las QS system and to investigate the effect
of environment (planktonic or biofilm mode of growth, absence or
presence of oxygen) and nutritional conditions on detection of transcripts
encoding QS-regulated virulence factors. Transcriptome results indicate
that the QS system is far more complex than previously proposed.
Interestingly, we found that many QS-regulated genes encoding virulence
products were expressed in all conditions investigated.},
booktitle = {Immunological Approaches against Nosocomial Infections},
issn = {0264-410X},
keywords = {Pseudomonas aeruginosa, Quorum-sensing, Virulence},
url = {http://www.sciencedirect.com/science/article/B6TD4-4D98BSB-1/2/241a275e32352b54a6c04dd476ca058e}
}
@ARTICLE{Wagschal2008,
author = {Wagschal, Alexandre and Sutherland, Heidi G. and Woodfine, Kathryn
and Henckel, Amandine and Chebli, Karim and Schulz, Reiner and Oakey,
Rebecca J. and Bickmore, Wendy A. and Feil, Robert},
title = {G9a Histone Methyltransferase Contributes to Imprinting in the Mouse
Placenta},
journal = {Mol. Cell. Biol.},
year = {2008},
volume = {28},
pages = {1104--1113},
number = {3},
month = feb,
abstract = {Whereas DNA methylation is essential for genomic imprinting, the importance
of histone methylation in the allelic expression of imprinted genes
is unclear. Imprinting control regions (ICRs), however, are marked
by histone H3-K9 methylation on their DNA-methylated allele. In the
placenta, the paternal silencing along the Kcnq1 domain on distal
chromosome 7 also correlates with the presence of H3-K9 methylation,
but imprinted repression at these genes is maintained independently
of DNA methylation. To explore which histone methyltransferase (HMT)
could mediate the allelic H3-K9 methylation on distal chromosome
7, and at ICRs, we generated mouse conceptuses deficient for the
SET domain protein G9a. We found that in the embryo and placenta,
the differential DNA methylation at ICRs and imprinted genes is maintained
in the absence of G9a. Accordingly, in embryos, imprinted gene expression
was unchanged at the domains analyzed, in spite of a global loss
of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific
imprinting of genes on distal chromosome 7 is impaired in the absence
of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3.
These findings provide the first evidence for the involvement of
an HMT and suggest that histone methylation contributes to imprinted
gene repression in the trophoblast.},
url = {http://mcb.asm.org/cgi/content/abstract/28/3/1104}
}
@ARTICLE{Wahl2004,
author = {Wahl, Melissa and Eddinger, Thomas J. and Hai, Chi-Ming},
title = {Sinusoidal length oscillation- and receptor-mediated mRNA expression
of myosin isoforms and {alpha}-SM actin in airway smooth muscle},
journal = {Am J Physiol Cell Physiol},
year = {2004},
volume = {287},
pages = {C1697--1708},
number = {6},
month = dec,
abstract = {We tested the hypothesis that sinusoidal length oscillation and receptor
activation interactively regulate the abundance of mRNA encoding
{alpha}-smooth muscle ({alpha}-SM) actin and myosin isoforms in intact
bovine tracheal smooth muscle. We found that sinusoidal length oscillation
significantly downregulated abundance of mRNA encoding {alpha}-SM
actin mRNA in unstimulated tissues but not in histamine- and carbachol-activated
tissues. This observation suggests antagonistic interactions between
mechanical stretch and receptor-mediated signal transduction in regulating
the abundance of mRNA encoding {alpha}-SM actin in intact airway
smooth muscle. This pattern of antagonistic interaction was also
observed in cholinergic receptor activation experiments. Whereas
carbachol significantly upregulated myosin heavy chain SMA isoform
expression in muscle strips held at slack length, carbachol did not
significantly alter SMA expression in muscle strips at sinusoidal
length oscillation. Carbachol also significantly upregulated GAPDH
expression in bovine tracheal smooth muscle. However, unlike SMA
expression, upregulation of GAPDH expression mediated by cholinergic
receptor activation appeared to be insensitive to the mechanical
state of airway smooth muscle. Unlike carbachol, histamine did not
significantly alter the expression of GAPDH, myosin heavy chain SMA
and SMB, myosin light chain LC17a and LC17b, and {alpha}-SM actin
in bovine tracheal smooth muscle. U0126 (10 {micro}M) completely
inhibited carbachol-induced ERK1/2 MAPK phosphorylation but did not
significantly affect carbachol-induced upregulation of GAPDH and
SMA expression, suggesting that the ERK1/2 MAPK pathway was not the
underlying mechanism. A potential implication of these findings is
that periodic stretching of airways during respiratory cycles may
modulate mRNA expression by receptor agonists in airway smooth muscle
cells in vivo.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/287/6/C1697}
}
@ARTICLE{Wahl2010,
author = {Wahl, Ramon and Zahiri, Alexander and Kämper, Jörg},
title = {The Ustilago maydis b mating type locus controls hyphal proliferation
and expression of secreted virulence factors in planta},
journal = {Molecular Microbiology},
year = {2010},
volume = {75},
pages = {208--220},
number = {1},
abstract = {Summary Sexual development in fungi is controlled by mating type loci
that prevent self-fertilization. In the phytopathogenic fungus Ustilago
maydis, the b mating type locus encodes two homeodomain proteins,
termed bE and bW. After cell fusion, a heterodimeric bE/bW complex
is formed if the proteins are derived from different alleles. The
bE/bW complex is required and sufficient to initiate pathogenic development
and sexual reproduction; for the stages of pathogenic development
succeeding plant penetration, however, its role was unclear. To analyse
b function during in planta development, we generated a temperature-sensitive
bEts protein by exchange of a single amino acid. bEts strains are
stalled in pathogenic development at restrictive temperature in planta,
and hyphae develop enlarged, bulbous cells at their tips that contain
multiple nuclei, indicating a severe defect in the control and synchronization
of cell cycle and cytokinesis. DNA array analysis of bEts mutant
strains in planta revealed a b-dependent regulation of genes encoding
secreted proteins that were shown to influence fungal virulence.
Our data demonstrate that in U. maydis the b heterodimer is not
only essential to establish the heterodikaryon after mating of two
compatible sporidia and to initiate fungal pathogenicity, but also
to sustain in planta proliferation and ensure sexual reproduction.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2009.06984.x}
}
@ARTICLE{Wahlin2010,
author = {Wahlin, Karl J. and Hackler, Laszlo and Adler, Ruben and Zack, Donald
J.},
title = {Alternative splicing of neuroligin and its protein distribution in
the outer plexiform layer of the chicken retina},
journal = {J. Comp. Neurol.},
year = {2010},
volume = {518},
pages = {4938--4962},
number = {24},
abstract = {Abstract Although synaptogenesis within the retina is obviously essential
for vision, mechanisms responsible for the initiation and maintenance
of retinal synapses are poorly understood. In addition to its scientific
interest, understanding retinal synapse formation is becoming clinically
relevant with ongoing efforts to develop transplantation-based approaches
for the treatment of retinal degenerative disease. To extend our
understanding, we have focused on the chick model system and have
studied the neuroligin family of neuronal adhesion factors that has
been shown to participate in synapse assembly in the brain. We identified
chicken orthologs of neuroligins 1, -3, and -4, but could find no
evidence of neuroligin 2. We investigated temporal and spatial patterns
of mRNA and protein expression during development using standard
polymerase chain reaction (RT-PCR), quantitative PCR (QPCR), laser-capture
microdissection (LCM), and confocal microscopy. At the mRNA level,
neuroligins were detected at the earliest period tested, embryonic
day (ED)5, which precedes the period of inner retina synaptogenesis.
Significant alternative splicing was observed through development.
While neuroligin gene products were generally detected in the inner
retina, low levels of neuroligin 1 mRNA were also detected in the
photoreceptor layer. Neuroligin 3 and -4 transcripts, on the other
hand, were only detected in the inner retina. At retinal synapses
neuroligin 1 protein was detected in the inner plexiform layer, but
its highest levels were detected in the outer plexiform layer on
the tips of horizontal cell dendrites. This work lays the groundwork
for future studies on the functional roles of the neuroligins within
the retina. J. Comp. Neurol. 518:4938–4962, 2010. © 2010 Wiley-Liss,
Inc.},
issn = {1096-9861},
keywords = {chick, horizontal cell, neurexin, photoreceptor, development, synaptogenesis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/cne.22499}
}
@ARTICLE{Waidner2011,
author = {Waidner, Lisa A. and Burnside, Joan and Anderson, Amy S. and Bernberg,
Erin L. and German, Marcelo A. and Meyers, Blake C. and Green, Pamela
J. and Morgan, Robin W.},
title = {A microRNA of infectious laryngotracheitis virus can downregulate
and direct cleavage of ICP4 mRNA},
journal = {Virology},
year = {2011},
volume = {411},
pages = {25--31},
number = {1},
month = mar,
abstract = {Viral microRNAs regulate gene expression using either translational
repression or mRNA cleavage and decay. Two microRNAs from infectious
laryngotracheitis virus (ILTV), iltv-miR-I5 and iltv-miR-I6, map
antisense to the ICP4 gene. Post-transcriptional repression by these
microRNAs was tested against a portion of the ICP4 coding sequence
cloned downstream of firefly luciferase. Luciferase activity was
downregulated by approximately 60% with the iltv-miR-I5 mimic. Addition
of an iltv-miR-I5 antagomiR or mutagenesis of the target seed sequence
alleviated this effect. The iltv-miR-I5 mimic, when co-transfected
with a plasmid expressing ICP4, reduced ICP4 transcript levels by
approximately 50%, and inhibition was relieved by an iltv-miR-I5
antagomiR. In infected cells, iltv-miR-I5 mediated cleavage at the
canonical site, as indicated by modified RACE analysis. Thus, in
this system, iltv-miR-I5 decreased ILTV ICP4 mRNA levels via transcript
cleavage and degradation. Downregulation of ICP4 could impact the
balance between the lytic and latent states of the virus in vivo.},
issn = {0042-6822},
keywords = {Infectious laryngotracheitis virus, Herpesvirus, microRNA, siRNA,
Transcription factor, ICP4},
url = {http://www.sciencedirect.com/science/article/pii/S0042682210007804}
}
@ARTICLE{Waigel2010,
author = {Waigel, S and Li, Xiaohong and Chen, Yinlu and Arumugam, Vennila
and Cooper, Nigel and Zacharias, Wolfgang},
title = {The UofL Microarray Facility: merger and new location},
journal = {BMC Bioinformatics},
year = {2010},
volume = {11},
pages = {P25},
number = {Suppl 4},
abstract = {:},
doi = {10.1186/1471-2105-11-S4-P25},
issn = {1471-2105},
url = {http://www.biomedcentral.com/1471-2105/11/S4/P25}
}
@ARTICLE{Wakai2010,
author = {Wakai, Jun and Kizaki, Keiichiro and Yamaguchi-Yamada, Misuzu and
Yamamoto, Yoshio},
title = {Differences in tyrosine hydroxylase expression after short-term hypoxia,
hypercapnia or hypercapnic hypoxia in rat carotid body},
journal = {Respiratory Physiology \& Neurobiology},
year = {2010},
volume = {173},
pages = {95--100},
number = {1},
month = aug,
abstract = {In the carotid body (CB), it has been reported that the expressions
of tyrosine hydroxylase (TH) mRNA and TH protein are enhanced by
exposure to hypoxia. However, it is not known whether CO2 affects
the expression of TH in the CB. We examined the expression of TH
mRNA and the immunoreactivity for TH in the CB of rats exposed to
hypoxia (10% O2), hypercapnia (10% CO2) and hypercapnic hypoxia (10%
O2 and 10% CO2) for 2-24 h. The expression of TH mRNA in the CB was
markedly enhanced in rats exposed to hypoxia for 4 h (6.6-fold),
6 h (6.0-fold) and 8 h (7.8-fold), and in rats exposed to hypercapnic
hypoxia for 12 h (4.8-fold). The most intense TH immunoreactivity
was observed in the CB from rats exposed to hypoxia for 12 and 24 h
and to hypercapnic hypoxia for 24 h. The expressions of TH mRNA and
the immunoreactivity for TH were not altered in the CB of rats exposed
to hypercapnia. It is suggested that CO2 does not affect TH expression
in the CB, and that it inhibits hypoxia-enhanced TH expression.},
issn = {1569-9048},
keywords = {Respiratory reflex, Hypoxia, Hypercapnia, Carotid body, Tyrosine hydroxylase,
Chemoreception},
url = {http://www.sciencedirect.com/science/article/B6X16-50GMMGX-2/2/e62ae310e832ed6cd190fa73fabb548e}
}
@ARTICLE{Wakankar2010,
author = {Wakankar, Aditya A. and Feeney, Maria B. and Rivera, Javier and Chen,
Yan and Kim, Michael and Sharma, Vikas K. and Wang, Y. John},
title = {Physicochemical Stability of the Antibody−Drug Conjugate Trastuzumab-DM1:
Changes due to Modification and Conjugation Processes},
journal = {Bioconjugate Chemistry},
year = {2010},
volume = {21},
pages = {1588-1595},
number = {9},
doi = {10.1021/bc900434c},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bc900434c},
url = {http://pubs.acs.org/doi/abs/10.1021/bc900434c}
}
@ARTICLE{WALIA2007,
author = {WALIA, HARKAMAL and WILSON, CLYDE and CONDAMINE, PASCAL and LIU,
XUAN and ISMAIL, ABDELBAGI M. and CLOSE, TIMOTHY J.},
title = {Large-scale expression profiling and physiological characterization
of jasmonic acid-mediated adaptation of barley to salinity stress},
journal = {Plant, Cell \& Environment},
year = {2007},
volume = {30},
pages = {410--421},
number = {4},
abstract = {ABSTRACT Barley (Hordeum vulgare L.) is a salt-tolerant member of
the Triticeae. Recent transcriptome studies on salinity stress response
in barley revealed regulation of jasmonic acid (JA) biosynthesis
and JA-responsive genes by salt stress. From that observation and
several other physiological reports, it was hypothesized that JA
is involved in the adaptation of barley to salt stress. Here we tested
that hypothesis by applying JA to barley plants and observing the
physiological responses and transcriptome changes. Photosynthetic
and sodium ion accumulation responses were compared after (1) salinity
stress, (2) JA treatment and (3) JA pre-treatment followed by salinity
stress. The JA-pre-treated salt-stressed plants accumulated strikingly
low levels of Na+ in the shoot tissue compared with untreated salt-stressed
plants after several days of exposure to stress. In addition, pre-treatment
with JA partially alleviated photosynthetic inhibition caused by
salinity stress. Expression profiling after a short-term exposure
to salinity stress indicated a considerable overlap between genes
regulated by salinity stress and JA application. Three JA-regulated
genes, arginine decarboxylase, ribulose 1·5-bisphosphate carboxylase/oxygenase
(Rubisco) activase and apoplastic invertase are possibly involved
in salinity tolerance mediated by JA. This work provides a reference
data set for further study of the role of JA in salinity tolerance
in barley and other plants species.},
issn = {1365-3040},
keywords = {photosynthesis, salt stress.},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3040.2006.01628.x}
}
@ARTICLE{Walia2005,
author = {Walia, Harkamal and Wilson, Clyde and Condamine, Pascal and Liu,
Xuan and Ismail, Abdelbagi M. and Zeng, Linghe and Wanamaker, Steve
I. and Mandal, Jayati and Xu, Jin and Cui, Xinping and Close, Timothy
J.},
title = {Comparative Transcriptional Profiling of Two Contrasting Rice Genotypes
under Salinity Stress during the Vegetative Growth Stage},
journal = {Plant Physiology},
year = {2005},
volume = {139},
pages = {822--835},
number = {2},
month = oct,
abstract = {Rice (Oryza sativa), a salt-sensitive species, has considerable genetic
variation for salt tolerance within the cultivated gene pool. Two
indica rice genotypes, FL478, a recombinant inbred line derived from
a population developed for salinity tolerance studies, and IR29,
the sensitive parent of the population, were selected for this study.
We used the Affymetrix rice genome array containing 55,515 probe
sets to explore the transcriptome of the salt-tolerant and salt-sensitive
genotypes under control and salinity-stressed conditions during vegetative
growth. Response of the sensitive genotype IR29 is characterized
by induction of a relatively large number of probe sets compared
to tolerant FL478. Salinity stress induced a number of genes involved
in the flavonoid biosynthesis pathway in IR29 but not in FL478. Cell
wall-related genes were responsive in both genotypes, suggesting
cell wall restructuring is a general adaptive mechanism during salinity
stress, although the two genotypes also had some differences. Additionally,
the expression of genes mapping to the Saltol region of chromosome
1 were examined in both genotypes. Single-feature polymorphism analysis
of expression data revealed that IR29 was the source of the Saltol
region in FL478, contrary to expectation. This study provides a genome-wide
transcriptional analysis of two well-characterized, genetically related
rice genotypes differing in salinity tolerance during a gradually
imposed salinity stress under greenhouse conditions.},
url = {http://www.plantphysiol.org/cgi/content/abstract/139/2/822}
}
@ARTICLE{Walia2009,
author = {Walia, Harkamal and Wilson, Clyde and Ismail, Abdelbagi and Close,
Timothy and Cui, Xinping},
title = {Comparing genomic expression patterns across plant species reveals
highly diverged transcriptional dynamics in response to salt stress},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {398},
number = {1},
abstract = {BACKGROUND:Rice and barley are both members of Poaceae (grass family)
but have a marked difference in salt tolerance. The molecular mechanism
underlying this difference was previously unexplored. This study
employs a comparative genomics approach to identify analogous and
contrasting gene expression patterns between rice and barley.RESULTS:A
hierarchical clustering approach identified several interesting expression
trajectories among rice and barley genotypes. There were no major
conserved expression patterns between the two species in response
to salt stress. A wheat salt-stress dataset was queried for comparison
with rice and barley. Roughly one-third of the salt-stress responses
of barley were conserved with wheat while overlap between wheat and
rice was minimal. These results demonstrate that, at transcriptome
level, rice is strikingly different compared to the more closely
related barley and wheat. This apparent lack of analogous transcriptional
programs in response to salt stress is further highlighted through
close examination of genes associated with root growth and development.CONCLUSION:The
analysis provides support for the hypothesis that conservation of
transcriptional signatures in response to environmental cues depends
on the genetic similarity among the genotypes within a species, and
on the phylogenetic distance between the species.},
doi = {10.1186/1471-2164-10-398},
issn = {1471-2164},
pubmedid = {19706179},
url = {http://www.biomedcentral.com/1471-2164/10/398}
}
@ARTICLE{Walisser2005,
author = {Walisser, Jacqueline A. and Glover, Edward and Pande, Kalyan and
Liss, Adam L. and Bradfield, Christopher A.},
title = {Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity
are mediated by different cell types},
journal = {PNAS},
year = {2005},
volume = {102},
pages = {17858--17863},
number = {49},
month = dec,
abstract = {The aryl hydrocarbon receptor (AHR) plays a role in three areas of
biology that include the adaptive metabolism of xenobiotics, the
toxic responses associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
(dioxin), and vascular remodeling of the developing embryo. To test
the hypothesis that receptor signaling in different cell types is
responsible for these aspects of AHR biology, we generated a conditional
Ahr allele where exon 2 is flanked by loxP sites. Through the use
of Cre-lox technology, we then investigated the role of AHR signaling
in hepatocytes or endothelial cells in mediating prototypical endpoints
of adaptive, toxic, or developmental signaling. Using this model,
we provide evidence that AHR signaling in endothelial/hematopoietic
cells is necessary for developmental closure of the ductus venosus,
whereas AHR signaling in hepatocytes is necessary to generate adaptive
and toxic responses of the liver in response to dioxin exposure.
Taken together, these data illustrate the importance of cell-specific
receptor signaling for the generation of distinct AHR-dependent physiological
outcomes.},
url = {http://www.pnas.org/cgi/content/abstract/102/49/17858}
}
@ARTICLE{Walker2010c,
author = {Walker, Amy K. and Yang, Fajun and Jiang, Karen and Ji, Jun-Yuan
and Watts, Jennifer L. and Purushotham, Aparna and Boss, Olivier
and Hirsch, Michael L. and Ribich, Scott and Smith, Jesse J. and
Israelian, Kristine and Westphal, Christoph H. and Rodgers, Joseph
T. and Shioda, Toshi and Elson, Sarah L. and Mulligan, Peter and
Najafi-Shoushtari, Hani and Black, Josh C. and Thakur, Jitendra K.
and Kadyk, Lisa C. and Whetstine, Johnathan R. and Mostoslavsky,
Raul and Puigserver, Pere and Li, Xiaoling and Dyson, Nicholas J.
and Hart, Anne C. and Naar, Anders M.},
title = {Conserved role of SIRT1 orthologs in fasting-dependent inhibition
of the lipid/cholesterol regulator SREBP},
journal = {Genes \& Dev.},
year = {2010},
volume = {24},
pages = {1403--1417},
number = {13},
month = jul,
abstract = {The sterol regulatory element-binding protein (SREBP) transcription
factor family is a critical regulator of lipid and sterol homeostasis
in eukaryotes. In mammals, SREBPs are highly active in the fed state
to promote the expression of lipogenic and cholesterogenic genes
and facilitate fat storage. During fasting, SREBP-dependent lipid/cholesterol
synthesis is rapidly diminished in the mouse liver; however, the
mechanism has remained incompletely understood. Moreover, the evolutionary
conservation of fasting regulation of SREBP-dependent programs of
gene expression and control of lipid homeostasis has been unclear.
We demonstrate here a conserved role for orthologs of the NAD+-dependent
deacetylase SIRT1 in metazoans in down-regulation of SREBP orthologs
during fasting, resulting in inhibition of lipid synthesis and fat
storage. Our data reveal that SIRT1 can directly deacetylate SREBP,
and modulation of SIRT1 activity results in changes in SREBP ubiquitination,
protein stability, and target gene expression. In addition, chemical
activators of SIRT1 inhibit SREBP target gene expression in vitro
and in vivo, correlating with decreased hepatic lipid and cholesterol
levels and attenuated liver steatosis in diet-induced and genetically
obese mice. We conclude that SIRT1 orthologs play a critical role
in controlling SREBP-dependent gene regulation governing lipid/cholesterol
homeostasis in metazoans in response to fasting cues. These findings
may have important biomedical implications for the treatment of metabolic
disorders associated with aberrant lipid/cholesterol homeostasis,
including metabolic syndrome and atherosclerosis.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/24/13/1403}
}
@ARTICLE{Walker2010a,
author = {Walker, Caroline and Meier, Susanne and Littlejohn, Mathew and Lehnert,
Klaus and Roche, John and Mitchell, Murray},
title = {Modulation of the maternal immune system by the pre-implantation
embryo},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {474},
number = {1},
abstract = {BACKGROUND:A large proportion of pregnancy losses occur during the
pre-implantation period, when the developing embryo is elongating
rapidly and signalling its presence to the maternal system. The molecular
mechanisms that prevent luteolysis and support embryo survival within
the maternal environment are not well understood. To gain a more
complete picture of these molecular events, genome-wide transcriptional
profiles of reproductive day 17 endometrial tissue were determined
in pregnant and cyclic Holstein-Friesian dairy cattle.RESULTS:Microarray
analyses revealed 1,839 and 1,189 differentially expressed transcripts
between pregnant and cyclic animals (with = 1.5 fold change in expression;
P-value < 0.05, MTC Benjamini-Hochberg) in caruncular and intercaruncular
endometrium respectively. Gene ontology and biological pathway analysis
of differentially expressed genes revealed enrichment for genes involved
in interferon signalling and modulation of the immune response in
pregnant animals.CONCLUSION:The maternal immune system actively surveys
the uterine environment during early pregnancy. The embryo modulates
this response inducing the expression of endometrial molecules that
suppress the immune response and promote maternal tolerance to the
embryo. During this period of local immune suppression, genes of
the innate immune response (in particular, antimicrobial genes) may
function to protect the uterus against infection.},
doi = {10.1186/1471-2164-11-474},
issn = {1471-2164},
pubmedid = {20707927},
url = {http://www.biomedcentral.com/1471-2164/11/474}
}
@ARTICLE{Walker2009,
author = {Walker, Caroline and Meier, Susanne and Mitchell, Murray and Roche,
John and Littlejohn, Mathew},
title = {Evaluation of real-time PCR endogenous control genes for analysis
of gene expression in bovine endometrium},
journal = {BMC Molecular Biology},
year = {2009},
volume = {10},
pages = {100},
number = {1},
abstract = {BACKGROUND:Quantitative real-time PCR gene expression results are
generally normalised using endogenous control genes. These reference
genes should be expressed at a constant level across all sample groups
in a study, and should not be influenced by study treatments or conditions.
There has been no systematic investigation of endogenous control
genes for bovine endometrium to date. The suitability of both commonly
used and novel endogenous control genes was evaluated in this study,
with the latter being selected from stably expressed transcripts
identified through microarray analysis of bovine endometrium. Fifteen
candidate endogenous control genes were assessed across different
tissue subtypes in pregnant and cycling Holstein-Friesian dairy cows
from two divergent genetic backgrounds.RESULTS:The expression profiles
of five commonly used endogenous control genes (GAPDH, PPIA, RPS9,
RPS15A, and UXT) and 10 experimentally derived candidate endogenous
control genes (SUZ12, C2ORF29, ZNF131, ACTR1A, HDAC1, SLC30A6, CNOT7,
DNAJC17, BBS2, and RANBP10) were analysed across 44 samples to determine
the most stably expressed gene. Gene stability was assessed using
the statistical algorithms GeNorm and Normfinder. All genes presented
with low overall variability (0.87 to 1.48% CV of Cq). However, when
used to normalise a differentially expressed gene (oxytocin receptor
- OXTR) in the samples, the reported relative gene expression levels
were significantly affected by the control gene chosen. Based on
the results of this analysis, SUZ12 is proposed as the most appropriate
control gene for use in bovine endometrium during early pregnancy
or the oestrus cycle.CONCLUSION:This study establishes the suitability
of novel endogenous control genes for comparing expression levels
in endometrial tissues of pregnant and cycling bovines, and demonstrates
the utility of microarray analysis as a method for identifying endogenous
control gene candidates.},
doi = {10.1186/1471-2199-10-100},
issn = {1471-2199},
pubmedid = {19878604},
url = {http://www.biomedcentral.com/1471-2199/10/100}
}
@ARTICLE{Walker2004,
author = {Walker, Daniel and Rolfe, Matthew and Thompson, Arthur and Moore,
Geoffrey R. and James, Richard and Hinton, Jay C. D. and Kleanthous,
Colin},
title = {Transcriptional Profiling of Colicin-Induced Cell Death of Escherichia
coli MG1655 Identifies Potential Mechanisms by Which Bacteriocins
Promote Bacterial Diversity},
journal = {J. Bacteriol.},
year = {2004},
volume = {186},
pages = {866--869},
number = {3},
month = feb,
abstract = {We report the transcriptional response of Escherichia coli MG1655
to damage induced by colicins E3 and E9, bacteriocins that kill cells
through inactivation of the ribosome and degradation of chromosomal
DNA, respectively. Colicin E9 strongly induced the LexA-regulated
SOS response, while colicin E3 elicited a broad response that included
the induction of cold shock genes, symptomatic of translational arrest.
Colicin E3 also increased the transcription of cryptic prophage genes
and other laterally acquired mobile elements. The transcriptional
responses to both these toxins suggest mechanisms that may promote
genetic diversity in E. coli populations, pointing to a more general
role for colicins in adaptive bacterial physiology than has hitherto
been realized.},
url = {http://jb.asm.org/cgi/content/abstract/186/3/866}
}
@ARTICLE{Walker2006,
author = {Walker, Douglas G. and Link, John and Lue, Lih-Fen and Dalsing-Hernandez,
Jessica E. and Boyes, Barry E.},
title = {Gene expression changes by amyloid {beta} peptide-stimulated human
postmortem brain microglia identify activation of multiple inflammatory
processes},
journal = {J. Leukoc. Biol.},
year = {2006},
volume = {79},
pages = {596--610},
number = {3},
month = mar,
abstract = {A central feature of the inflammatory pathology in Alzheimer's disease
is activated microglia clustered around aggregated amyloid {beta}
(A{beta}) peptide-containing plaques. In vitro-cultured microglia
can be activated to an inflammatory state by aggregated A{beta} with
the induction of a range of different neurotoxic factors and provide
a model system for studying microglia A{beta} interactions. Gene
expression responses of human postmortem brain-derived microglia
to aggregated A{beta} were measured using whole genome microarrays
to address the hypothesis that A{beta} interactions with human microglia
primarily induce proinflammatory genes and not activation of genes
involved in A{beta} phagocytosis and removal. The results demonstrated
that A{beta} activation of microglia induced a large alteration in
gene transcription including activation of many proinflammatory cytokines
and chemokines, most notably, interleukin (IL)-1{beta}, IL-8, and
matrix metalloproteinases (MMP), including MMP1, MMP3, MMP9, MMP10,
and MMP12. All of these genes could amplify ongoing inflammation,
resulting in further neuronal loss. Changes in expression of receptors
associated with A{beta} phagocytosis did not match the changes in
proinflammatory gene expression. Time-course gene expression profiling,
along with real-time polymerase chain reaction validation of expression
changes, demonstrated an acute phase of gene induction for many proinflammatory
genes but also chronic activation for many other potentially toxic
products. These chronically activated genes included indoleamine
2,3-dioxygenase and kynureninase, which are involved in formation
of the neurotoxin quinolinic acid, and S100A8, a potential proinflammatory
chemokine. These studies show that activation of microglia by A{beta}
induces multiple genes that could be involved in inflammatory responses
contributing to neurodegenerative processes.},
url = {http://www.jleukbio.org/cgi/content/abstract/79/3/596}
}
@ARTICLE{Walker2010b,
author = {Walker, D. K. and Titgemeyer, E. C. and Baxa, T. J. and Chung, K.
Y. and Johnson, D. E. and Laudert, S. B. and Johnson, B. J.},
title = {Effects of ractopamine and sex on serum metabolites and skeletal
muscle gene expression in finishing steers and heifers},
journal = {J Anim Sci},
year = {2010},
volume = {88},
pages = {1349--1357},
number = {4},
month = apr,
abstract = {We evaluated growth-related responses to ractopamine in steers and
heifers. Sixteen Angus steers (512 kg) and 16 Angus heifers (473
kg) housed in individual pens were used in a complete block design.
At 90 to 97 d before the experiment, steers were implanted with 120
mg of trenbolone acetate and 24 mg of estradiol-17{beta} (Component
TE-S) and heifers were implanted with 140 mg of trenbolone acetate
and 14 mg of estradiol-17{beta} (Component TE-H). Treatments were
arranged as a 2 x 2 factorial and included sex (steer vs. heifer)
and ractopamine-HCl (0 or 200 mg/d). Cattle were fed a diet based
on steam-flaked corn once daily. Blood and LM and biceps femoris
(BF) biopsy samples were collected on d 0 (before ractopamine feeding)
and after 14 and 28 d of ractopamine feeding. Serum insulin concentrations
were not affected by ractopamine or sex. Serum IGF-I concentrations
were greater in steers than heifers (P < 0.001), and steers demonstrated
greater IGF-I mRNA expression in BF than heifers (P = 0.05). Ractopamine
decreased serum IGF-I concentrations in heifers on d 14, but increased
serum IGF-I concentrations in steers on d 28 (sex x ractopamine x
day interaction; P = 0.03). Ractopamine did not affect (P [≥]
0.19) mRNA expression of IGF-I, IGFBP-3, or calpastatin in BF or
LM. However, ractopamine led to increases in LM expression of IGFBP-5
in heifers, but to decreases in expression in steers (ractopamine
x sex interaction; P = 0.04). Ractopamine decreased myosin heavy
chain IIA mRNA expression in BF (P = 0.04) but not in LM (P = 0.99).
Ractopamine decreased {beta}2-receptor mRNA expression in LM of steers
on d 14, but not on d 28; in contrast, expression of {beta}2-receptor
mRNA in LM of heifers was not affected by ractopamine (sex x ractopamine
x day interaction; P = 0.03). Although there were a few criteria
for which ractopamine led to differences in response between steers
and heifers, there were no striking disparities to suggest that the
effectiveness of ractopamine would markedly differ between sexes.},
url = {http://jas.fass.org/cgi/content/abstract/88/4/1349}
}
@ARTICLE{Walker2005,
author = {Walker, Diana L. and Vacha, Scott J. and Kirby, Margaret L. and Lo,
Cecilia W.},
title = {Connexin43 deficiency causes dysregulation of coronary vasculogenesis},
journal = {Developmental Biology},
year = {2005},
volume = {284},
pages = {479--498},
number = {2},
month = aug,
abstract = {The connexin43 knockout (Cx43[alpha]1 KO) mouse dies at birth from
outflow obstruction associated with infundibular pouches. To elucidate
the origin of the infundibular pouches, we used microarray analysis
to investigate gene expression changes in the pouch tissue. We found
elevated expression of many genes encoding markers for vascular smooth
muscle (VSM), endothelial cells, and fibroblasts, cell types that
are epicardially derived and essential for coronary vasculogenesis.
This was accompanied by increased expression of VEGF and genes in
the TGF[beta] and VEGF/Notch/Eph cell-signaling pathways known to
regulate vasculogenesis/angiogenesis. Using immunohistochemistry
and a VSM lacZ reporter gene, we confirmed an abundance of ectopic
VSM and endothelial cells in the infundibular pouch and in some regions
of the right ventricle forming secondary pouches. This was associated
with distinct thinning of the compact myocardium. TUNEL labeling
showed increased apoptosis in the pouch tissue, in agreement with
the finding of altered expression of many apoptotic genes. Defects
in vascular remodeling were indicated by a marked reduction in the
branching complexity of the distal coronary arteries. In the near
term KO mouse, we also observed a profusion of large coronary vascular
plexuses subepicardially. This was associated with elevated epicardial
expression of VEGF and abnormal epicardial cell morphology. Together,
these observations indicate that dysregulated coronary vasculogenesis
plays a pivotal role in formation of the infundibular pouches and
suggests an essential role for Cx43[alpha]1 gap junctions in coronary
vasculogenesis and vascular remodeling.},
issn = {0012-1606},
keywords = {Coronary vessels, Connexin43, Knockout, VEGF, Vascular smooth muscle,
Endothelial cells, Heart development},
url = {http://www.sciencedirect.com/science/article/B6WDG-4GP1VN7-2/2/bd239847d19267e969ce4eb42ee91c4a}
}
@ARTICLE{Walker2009a,
author = {Walker, Deena M. and Juenger, Thomas E. and Gore, Andrea C.},
title = {Developmental Profiles of Neuroendocrine Gene Expression in the Preoptic
Area of Male Rats},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {2308--2316},
number = {5},
month = may,
abstract = {Reproductive function is controlled by GnRH cells and their steroid-sensitive
regulatory inputs. The proper maturation of this system is critical
to sexual development and maintenance of adult function. However,
the molecular mechanisms underlying these developmental changes,
and the potential roles of gonadal hormones in sculpting these processes,
have not been fully explored. We performed a developmental profile
from postnatal day (P) 1 through P60 of a network of five genes in
the preoptic area (POA) that are critical to reproduction in male
Sprague Dawley rats. GnRH, estrogen receptors-{alpha}, and -{beta},
androgen receptor (AR), and progesterone receptor (PR) mRNAs in the
POA were assayed, and serum hormones were measured, in developing
male rats. We also used a Taqman low-density array to identify candidate
genes that may be important in development. Of the five targeted
genes, only AR and PR changed robustly (7- and 3- to 4-fold increases,
respectively) during development. All of the gonadal serum hormones
changed markedly and with very different patterns from their receptor
mRNAs: testosterone decreased from P1 to P30 and then increased to
P60; progesterone peaked on P30; and estradiol decreased from P1
to P30. Using the Taqman low-density array, we identified several
genes that changed dramatically in the POA with development, particularly
G protein-coupled receptor 30, IGF-I, vitamin D receptor, estrogen-related
receptor-{alpha}, and thyroid receptor-{alpha}. Our data demonstrate
developmental stage-specific changes in neuroendocrine genes, particularly
AR and PR. Moreover, the relationships between hormones and their
corresponding receptors undergo dynamic changes across development
in male rats.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/5/2308}
}
@ARTICLE{Walker2010,
author = {Walker, Emily and Chang, Wing Y. and Hunkapiller, Julie and Cagney,
Gerard and Garcha, Kamal and Torchia, Joseph and Krogan, Nevan J.
and Reiter, Jeremy F. and Stanford, William L.},
title = {Polycomb-like 2 Associates with PRC2 and Regulates Transcriptional
Networks during Mouse Embryonic Stem Cell Self-Renewal and Differentiation},
journal = {Cell Stem Cell},
year = {2010},
volume = {6},
pages = {153--166},
number = {2},
month = feb,
abstract = {Summary Polycomb group (PcG) proteins are conserved epigenetic transcriptional
repressors that control numerous developmental gene expression programs
and have recently been implicated in modulating embryonic stem cell
(ESC) fate. We identified the PcG protein PCL2 (polycomb-like 2)
in a genome-wide screen for regulators of self-renewal and pluripotency
and predicted that it would play an important role in mouse ESC-fate
determination. Using multiple biochemical strategies, we provide
evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated
protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened
self-renewal characteristics, defects in differentiation, and altered
patterns of histone methylation. Integration of global gene expression
and promoter occupancy analyses allowed us to identify PCL2 and PRC2
transcriptional targets and draft regulatory networks. We describe
the role of PCL2 in both modulating transcription of ESC self-renewal
genes in undifferentiated ESCs as well as developmental regulators
during early commitment and differentiation.},
issn = {1934-5909},
keywords = {STEMCELL},
url = {http://www.sciencedirect.com/science/article/B8G3V-4YB0R9D-C/2/ee4d6bceca764f44811affabf1eae941}
}
@BOOK{Walker2006a,
title = {Microfluidics},
publisher = {John Wiley \& Sons, Inc.},
year = {2006},
author = {Walker, Glenn M.},
pages = {--},
abstract = {This article provides a brief overview of the fluid phenomena that
become prominent at the microscale. Microfluidic devices can be created
that take advantage of these phenomena to provide novel functionality.
The modeling of microfluidic systems, from the microscopic to the
macroscopic level is presented. Pumping methods using pressure and
electric fields are discussed. Methods of fabricating microfluidic
devices are examined. Finally, examples of biomedical devices that
use microfluidics are given.},
booktitle = {Encyclopedia of Medical Devices and Instrumentation},
issn = {9780471732877},
keywords = {microfluidics, diffusion, reynolds number, laminar flow, fluid mechanics,
bio-micro-electro-mechanical systems, capillary electrophoresis,
point-of-care testing},
url = {http://dx.doi.org/10.1002/0471732877.emd288}
}
@ARTICLE{Walker2008,
author = {Walker, Michelle and Phillips, Carol A.},
title = {Alicyclobacillus acidoterrestris: an increasing threat to the fruit
juice industry?},
journal = {International Journal of Food Science \& Technology},
year = {2008},
volume = {43},
pages = {250--260},
number = {2},
abstract = {Summary The quality of food can be defined in various ways with processors
and consumers considering flavour, odour and appearance as well as
extended shelf life among the most important of its attributes. Spoilage
of food by bacterial contamination may occur at any point during
the processing, altering any one, or all, of these characteristics,
rendering the product unusable. Alicyclobacillus spp. and Alicyclobacillus
acidoterrestris, in particular, are emerging food spoilage organisms
in the fruit juice and fruit juice products industry. Spores of the
latter are able to survive heat treatments presently used in the
industry and their elimination from products may be used as a measure
of the effectiveness of any processing protocol to remove potential
spoilage. This paper reviews the history, methods of detection, both
traditional and rapid and the protocols that may be effective in
controlling the growth of the organism and hence spoilage in the
finished product.},
issn = {1365-2621},
keywords = {Alicyclobacillus acidoterrestris, Alicyclobacillus spp, control, detection,
fruit juices},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2621.2006.01427.x}
}
@ARTICLE{Walker2006b,
author = {Walker, Stephen J. and Wang, Yulei and Grant, Kathleen A. and Chan,
Frances and Hellmann, Gary M.},
title = {Long versus short oligonucleotide microarrays for the study of gene
expression in nonhuman primates},
journal = {Journal of Neuroscience Methods},
year = {2006},
volume = {152},
pages = {179--189},
number = {1-2},
month = apr,
abstract = {The high degree of sequence similarity between human and nonhuman
primate (NHP) genomic DNA suggests that human genome sequence-based
DNA microarrays may be used effectively to study gene expression
in NHP disease models. In the present study, two distinct commercially
available human genome microarray platforms, the Affymetrix HG U133A
GeneChip® System utilizing Human Genome U133A GeneChips® and the
Applied Biosystems Expression Array System utilizing the Human Genome
Survey Microarray, were used to identify and characterize gene expression
changes in the anterior cerebellum of a macaque monkey model of human
alcoholism. The Affymetrix microarray consists of eleven short oligonucleotide
probe sets for each gene while the Applied Biosystems Microarray
uses a single long oligonucleotide per gene. Cross-mapping of probes
revealed a total of 11,542 genes that are represented on both microarray
platforms. Absolute measures of gene expression ("present calls")
from the cerebellum RNA samples were 65-70% (Applied Biosystems Expression
Array System) and 27-30% (AffymetrixGeneChip® System) among these
common gene targets. Analysis of variance (ANOVA; p < 0.05; >1.2
fold change; detected on at least 50% of the arrays) indicated 932
and 515 differentially expressed genes for the Applied Biosystems
and Affymetrix microarrays, respectively. Significance analysis of
microarrays (SAM) identified 255 significant genes at 5% false discovery
rate (FDR) for the Applied Biosystems data set and five significant
genes at 60% FDR (minimum FDR) for the Affymetrix data set. TaqMan®
assay-based real-time PCR validation of a number of differentially-expressed
genes yielded results that agreed well with the array data in the
majority of comparisons. This study demonstrates that human sequence-based
DNA arrays can be used effectively to detect differential gene expression
in an NHP disease model and provides evidence that the use of this
long oligonucleotide-based microarray platform may be more suitable
for cross-species gene expression studies than a short oligonucleotide-based
system.},
issn = {0165-0270},
keywords = {Microarray, Alcoholism, Nonhuman primate, Gene expression, Cerebellum,
Oligonucleotide},
url = {http://www.sciencedirect.com/science/article/B6T04-4HDG966-3/2/838ec904d2e35ffa57840e7a251caa86}
}
@ARTICLE{Wall2011,
author = {Wall, Christopher E. and Cozza, Steven and Riquelme, Cecilia A. and
McCombie, W. Richard and Heimiller, Joseph K. and Marr, Thomas G.
and Leinwand, Leslie A.},
title = {Whole transcriptome analysis of the fasting and fed Burmese python
heart: insights into extreme physiological cardiac adaptation},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {69--76},
number = {2},
month = jan,
abstract = {The infrequently feeding Burmese python (Python molurus) experiences
significant and rapid postprandial cardiac hypertrophy followed by
regression as digestion is completed. To begin to explore the molecular
mechanisms of this response, we have sequenced and assembled the
fasted and postfed Burmese python heart transcriptomes with Illumina
technology using the chicken (Gallus gallus) genome as a reference.
In addition, we have used RNA-seq analysis to identify differences
in the expression of biological processes and signaling pathways
between fasted, 1 day postfed (DPF), and 3 DPF hearts. Out of a combined
transcriptome of [~]2,800 mRNAs, 464 genes were differentially expressed.
Genes showing differential expression at 1 DPF compared with fasted
were enriched for biological processes involved in metabolism and
energetics, while genes showing differential expression at 3 DPF
compared with fasted were enriched for processes involved in biogenesis,
structural remodeling, and organization. Moreover, we present evidence
for the activation of physiological and not pathological signaling
pathways in this rapid, novel model of cardiac growth in pythons.
Together, our data provide the first comprehensive gene expression
profile for a reptile heart.},
comment = {10.1152/physiolgenomics.00162.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/2/69}
}
@ARTICLE{Wall2010,
author = {Wall, E.H. and McFadden, T.B.},
title = {The effects of milk removal or four-times-daily milking on mammary
expression of genes involved in the insulin-like growth factor-I
axis},
journal = {J Dairy Sci},
year = {2010},
volume = {93},
pages = {4062--4070},
number = {9},
month = sep,
abstract = {Frequent milking of dairy cows during early lactation elicits both
an immediate increase in milk yield and a partial carryover effect
that persists to the end of lactation. We hypothesized that the immediate
response would be associated with a local increase in insulin-like
growth factor (IGF)-I signaling and a consequent increase in mammary
growth. Four multiparous cows were assigned at parturition to unilateral
frequent milking [UFM; milking of the left udder half twice daily
(2×; 0230 and 1430h); milking of the right udder half 4 times daily
(4×; 0230, 0530, 1430, and 1730h)]. Mammary biopsies were obtained
from both udder halves at 5 d in milk at 0530h (immediately after
4× glands were milked). Incorporation of [3H]-thymidine into DNA
and mammary cell apoptosis were not affected by UFM. Because biopsies
were obtained when udder halves were at different postmilking intervals,
our results reflected both the acute, transient mammary response
to milking and the sustained mammary response to frequent milking
treatment. We further hypothesized that the acute, transient response
involves mechanisms distinct from those regulating the sustained
response to frequent milking. To test that hypothesis, mammary biopsies
were obtained from UFM cows (n=5) at 0500h, when time postmilking
was the same for both udder halves. Mammary cell apoptosis was not
affected by UFM. Expression of genes involved in the IGF-I axis was
analyzed to identify acute responses associated with milking, per
se, versus sustained responses to frequent milking treatment. Removal
of milk from 4× glands was associated with an acute increase in
expression of IGF binding protein-1, -3, and -4 mRNA in 2× glands,
whereas IGF-I expression was increased by frequent milking treatment.
These effects, however, were significant only for expression of IGF
binding protein-3. Expression of IGF-I receptor did not differ because
of milking frequency but was higher in both udder halves immediately
postmilking, indicating a systemic effect. We conclude that several
genes of the IGF-I axis respond to milking, per se, or frequent milking
treatment, via at least 3 distinct patterns. Increased milking frequency
does not alter mammary cell proliferation or apoptosis at 5 d in
milk; however, it may increase the bioavailability of IGF-I in the
mammary gland. Moreover, the increase in local expression of IGF-I
in 4× udder halves indicates a role for this gene in the immediate
milk yield response to frequent milking during early lactation.},
issn = {0022-0302},
keywords = {insulin-like growth factor-I, local regulation, mammary growth, milking
frequency},
publisher = {American Dairy Science Association},
refid = {S0022-0302(10)00431-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0022030210004315?showall=true}
}
@ARTICLE{Wall2009,
author = {Wall, P Kerr and Leebens-Mack, Jim and Chanderbali, André and Barakat,
Abdelali and Wolcott, Erik and Liang, Haiying and Landherr, Lena
and Tomsho, Lynn and Hu, Yi and Carlson, John and Ma, Hong and Schuster,
Stephan and Soltis, Douglas and Soltis, Pamela and Altman, Naomi
and dePamphilis, Claude},
title = {Comparison of next generation sequencing technologies for transcriptome
characterization},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {347},
number = {1},
abstract = {BACKGROUND:We have developed a simulation approach to help determine
the optimal mixture of sequencing methods for most complete and cost
effective transcriptome sequencing. We compared simulation results
for traditional capillary sequencing with "Next Generation" (NG)
ultra high-throughput technologies. The simulation model was parameterized
using mappings of 130,000 cDNA sequence reads to the Arabidopsis
genome (NCBI Accession SRA008180.19). We also generated 454-GS20
sequences and de novo assemblies for the basal eudicot California
poppy (Eschscholzia californica) and the magnoliid avocado (Persea
americana) using a variety of methods for cDNA synthesis.RESULTS:The
Arabidopsis reads tagged more than 15,000 genes, including new splice
variants and extended UTR regions. Of the total 134,791 reads (13.8
MB), 119,518 (88.7%) mapped exactly to known exons, while 1,117 (0.8%)
mapped to introns, 11,524 (8.6%) spanned annotated intron/exon boundaries,
and 3,066 (2.3%) extended beyond the end of annotated UTRs. Sequence-based
inference of relative gene expression levels correlated significantly
with microarray data. As expected, NG sequencing of normalized libraries
tagged more genes than non-normalized libraries, although non-normalized
libraries yielded more full-length cDNA sequences. The Arabidopsis
data were used to simulate additional rounds of NG and traditional
EST sequencing, and various combinations of each. Our simulations
suggest a combination of FLX and Solexa sequencing for optimal transcriptome
coverage at modest cost. We have also developed ESTcalc http://fgp.huck.psu.edu/NG_Sims/ngsim.pl,
an online webtool, which allows users to explore the results of this
study by specifying individualized costs and sequencing characteristics.CONCLUSION:NG
sequencing technologies are a highly flexible set of platforms that
can be scaled to suit different project goals. In terms of sequence
coverage alone, the NG sequencing is a dramatic advance over capillary-based
sequencing, but NG sequencing also presents significant challenges
in assembly and sequence accuracy due to short read lengths, method-specific
sequencing errors, and the absence of physical clones. These problems
may be overcome by hybrid sequencing strategies using a mixture of
sequencing methodologies, by new assemblers, and by sequencing more
deeply. Sequencing and microarray outcomes from multiple experiments
suggest that our simulator will be useful for guiding NG transcriptome
sequencing projects in a wide range of organisms.},
doi = {10.1186/1471-2164-10-347},
issn = {1471-2164},
pubmedid = {19646272},
url = {http://www.biomedcentral.com/1471-2164/10/347}
}
@ARTICLE{Wallace2008,
author = {Wallace, Darren P. and Quante, Megan T. and Reif, Gail A. and Nivens,
Emily and Ahmed, Farhana and Hempson, Scott J. and Blanco, Gustavo
and Yamaguchi, Tamio},
title = {Periostin induces proliferation of human autosomal dominant polycystic
kidney cells through {alpha}V-integrin receptor},
journal = {Am J Physiol Renal Physiol},
year = {2008},
volume = {295},
pages = {F1463--1471},
number = {5},
month = nov,
abstract = {Progressive renal enlargement due to the growth of innumerable fluid-filled
cysts is a central pathophysiological feature of autosomal dominant
polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge
slowly and damage noncystic parenchyma by mechanisms that have not
been clearly defined. In a microarray analysis of cultured human
ADPKD cyst epithelial cells, periostin mRNA was overexpressed 15-fold
compared with normal human kidney (NHK) cells. Periostin, initially
identified in osteoblasts, is not expressed in normal adult kidneys
but is expressed transiently during renal development. We found periostin
in cyst-lining cells in situ in the extracellular matrix adjacent
to the cysts and within cyst fluid. ADPKD cells secreted periostin
across luminal and basolateral plasma membranes. Periostin increased
proliferation of cyst epithelial cells 27.9 {+/-} 3.1% (P < 0.001)
above baseline and augmented in vitro cyst growth but did not affect
proliferation of normal renal cells. Expression of {alpha}V-integrin,
a periostin receptor, was ninefold higher in ADPKD cells compared
with NHK cells, and antibodies that block {alpha}V-integrin inhibited
periostin-induced cell proliferation. We conclude that periostin
is a novel autocrine mitogen secreted by mural epithelial cells with
the potential to accelerate cyst growth and promote interstitial
remodeling in ADPKD.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/295/5/F1463}
}
@ARTICLE{Wallace2006,
author = {Wallace, Jacqueline M. and Matsuzaki, Masatoshi and Milne, John and
Aitken, Raymond},
title = {Late but Not Early Gestational Maternal Growth Hormone Treatment
Increases Fetal Adiposity in Overnourished Adolescent Sheep},
journal = {Biol Reprod},
year = {2006},
volume = {75},
pages = {231--239},
number = {2},
month = aug,
abstract = {In the overnourished adolescent sheep, maternal tissue synthesis is
promoted at the expense of placental growth and leads to a major
decrease in lamb birth weight at term. Maternal growth hormone (GH)
concentrations are attenuated in these pregnancies, and it was recently
demonstrated that exogenous GH administration throughout the period
of placental proliferation stimulates uteroplacental and fetal development
by Day 81 of gestation. The present study aimed to determine whether
these effects persist to term and to establish whether GH affects
fetal growth and body composition by increasing placental size or
by altering maternal metabolism. Adolescent recipient ewes were implanted
with singleton embryos on Day 4 postestrus. Three groups of ewes
offered a high dietary intake were injected twice daily with recombinant
bovine GH from Days 35 to 65 of gestation (high intake plus early
GH) or from Days 95 to 125 of gestation (high intake plus late GH)
or remained untreated (high intake only). A fourth moderate-intake
group acted as optimally nourished controls. Pregnancies were terminated
at Day 130 of gestation (6 per group) or were allowed to progress
to term (8-10 per group). GH administration elevated maternal plasma
concentrations of GH, insulin, glucose, and nonesterified fatty acids
during the defined treatment windows, while urea concentrations were
decreased. At Day 130, GH treatment had reduced the maternal adiposity
score, percentage of fat in the carcass, and internal fat depots
and leptin concentrations, predominantly in the high-intake plus
late GH group. Placental weight was lower in high-intake vs. control
dams but independent of GH treatment. In contrast, fetal weight was
elevated by late GH treatment, and these fetuses had higher relative
carcass fat content, perirenal fat mass, and liver glycogen concentrations
than all other groups. Expression of leptin mRNA in fetal perirenal
fat and fetal plasma leptin concentrations were not significantly
altered by maternal nutritional intake or GH. In pregnancies proceeding
to term, the duration of gestation, fetal placental mass, and lamb
birth weight were reduced in high-intake compared with control dams
but were not significantly affected by GH treatment. In conclusion,
exogenous GH has profound effects on maternal endocrinology, metabolism,
and body composition when administered during early and late pregnancy.
Treatment during late pregnancy has a modest effect on fetal growth
independent of placental size and a profound effect on fetal adiposity,
which may have implications beyond the fetal period.},
url = {http://www.biolreprod.org/cgi/content/abstract/75/2/231}
}
@ARTICLE{Wallace2004,
author = {Wallace, Jacqueline M. and Milne, John S. and Aitken, Raymond P.},
title = {Maternal Growth Hormone Treatment from Day 35 to 80 of Gestation
Alters Nutrient Partitioning in Favor of Uteroplacental Growth in
the Overnourished Adolescent Sheep},
journal = {Biol Reprod},
year = {2004},
volume = {70},
pages = {1277--1285},
number = {5},
month = may,
abstract = {Overnourishing the pregnant adolescent ewe promotes maternal tissue
synthesis at the expense of placental growth and leads to a major
reduction in lamb birth weight at term. Growth hormone (GH) secretion
is attenuated in these overnourished dams and the maternal somatotrophic
axis may play a key role in coordinating nutrient usage in the pregnant
adolescent. Thus we investigated whether increasing maternal GH during
the period of rapid placental proliferation alters nutrient partitioning
between the maternal, placental, and fetal tissues as assessed at
Day 81 of gestation. Adolescent recipient ewes were implanted with
singleton embryos, derived from superovulated dams and a single sire
on Day 4 postestrus. Thereafter, the ewes were offered either a high
(H) or moderate intake (M) of the same complete diet. From Day 35
to 80 of gestation, ewes were either injected twice daily (s.c. at
0800 and 1800 h) with recombinant bovine GH (bGH, 0.14 mg/kg live
weight/day) or remained untreated (n = 8 ewes per group). Maternal
concentrations of GH, insulin, insulin-like growth factor (IGF-1),
glucose, and non-esterified fatty acids (NEFAs) were higher, and
leptin secretion lower, in bGH-treated dams from both nutritional
groups. Maternal body weight gain was higher in H versus M groups
and was independent of bGH treatment. Treatment with bGH reduced
relative perirenal and carcass fat deposition and increased carcass
protein content in both H and M dams. Uteroplacental mass (uterus
+ placentomes + fetal membranes) averaged 1099, 1069, 1112, and 1754
g in M, H, M+GH, and H+GH groups. This significant increase in uteroplacental
development in the H+GH group was associated with higher fetal kidney
and liver weights and elevated fetal insulin, glucose, and lactate
concentrations. Treatment with bGH also induced polyhydramnios in
the H group. The transplacental glucose gradient was increased twofold
in the H+GH group but placental GLUT- 1 and GLUT-3 expression was
unaffected. In conclusion, administration of GH during the period
of rapid placental proliferation alters endocrine status and thus
nutrient partitioning in the overnourished adolescent dam in favor
of uteroplacental and fetal growth. It remains to be established
whether these effects are due wholly to alterations in maternal metabolism
or if they also reflect an effect of bGH and/or the IGF system at
the level of the uteroplacenta.},
url = {http://www.biolreprod.org/cgi/content/abstract/70/5/1277}
}
@ARTICLE{Wallace2004a,
author = {Wallace, Karin J. and Wallis, Robert H. and Collins, Stephan C. and
Argoud, Karene and Kaisaki, Pamela J. and Ktorza, Alain and Woon,
Peng Y. and Bihoreau, Marie-Therese and Gauguier, Dominique},
title = {Quantitative trait locus dissection in congenic strains of the Goto-Kakizaki
rat identifies a region conserved with diabetes loci in human chromosome
1q},
journal = {Physiol Genomics},
year = {2004},
volume = {19},
pages = {1--10},
number = {1},
month = sep,
abstract = {Genetic studies in human populations and rodent models have identified
regions of human chromosome 1q21-25 and rat chromosome 2 showing
evidence of significant and replicated linkage to diabetes-related
phenotypes. To investigate the relationship between the human and
rat diabetes loci, we fine mapped the rat locus Nidd/gk2 linked to
hyperinsulinemia in an F2 cross derived from the diabetic (type 2)
Goto-Kakizaki (GK) rat and the Brown Norway (BN) control rat, and
carried out its genetic and pathophysiological characterization in
BN.GK congenic strains. Evidence of glucose intolerance and enhanced
insulin secretion in a congenic strain allowed us to localize the
underlying diabetes gene(s) in a rat chromosomal interval of [~]3-6
cM conserved with an 11-Mb region of human 1q21-23. Positional diabetes
candidate genes were tested for transcriptional changes between congenics
and controls and sequence variations in a panel of inbred rat strains.
Congenic strains of the GK rats represent powerful novel models for
accurately defining the pathophysiological impact of diabetes gene(s)
at the locus Nidd/gk2 and improving functional annotations of diabetes
candidates in human 1q21-23.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/19/1/1}
}
@ARTICLE{Wallace2008a,
author = {Wallace, Tiffany A. and Prueitt, Robyn L. and Yi, Ming and Howe,
Tiffany M. and Gillespie, John W. and Yfantis, Harris G. and Stephens,
Robert M. and Caporaso, Neil E. and Loffredo, Christopher A. and
Ambs, Stefan},
title = {Tumor Immunobiological Differences in Prostate Cancer between African-American
and European-American Men},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {927--936},
number = {3},
month = feb,
abstract = {The incidence and mortality rates of prostate cancer are significantly
higher in African-American men when compared with European-American
men. We tested the hypothesis that differences in tumor biology contribute
to this survival health disparity. Using microarray technology, we
obtained gene expression profiles of primary prostate tumors resected
from 33 African-American and 36 European-American patients. These
tumors were matched on clinical variables. We also evaluated 18 nontumor
prostate tissues from seven African-American and 11 European-American
patients. The resulting datasets were analyzed for expression differences
on the gene and pathway level comparing African-American with European-American
patients. Our analysis revealed a significant number of genes, e.g.,
162 transcripts at a false-discovery rate of [≤]5% to be differently
expressed between African-American and European-American patients.
Using a disease association analysis, we identified a common relationship
of these transcripts with autoimmunity and inflammation. These findings
were corroborated on the pathway level with numerous differently
expressed genes clustering in immune response, stress response, cytokine
signaling, and chemotaxis pathways. Several known metastasis-promoting
genes, including autocrine mobility factor receptor, chemokine (C-X-C
motif) receptor 4, and matrix metalloproteinase 9, were more highly
expressed in tumors from African-Americans than European-Americans.
Furthermore, a two-gene tumor signature that accurately differentiated
between African-American and European-American patients was identified.
This finding was confirmed in a blinded analysis of a second sample
set. In conclusion, the gene expression profiles of prostate tumors
indicate prominent differences in tumor immunobiology between African-American
and European-American men. The profiles portray the existence of
a distinct tumor microenvironment in these two patient groups. [Cancer
Res 2008;68(3):927-36]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/3/927}
}
@ARTICLE{Wallenborn2008,
author = {Wallenborn, J. Grace and Evansky, Paul and Shannahan, Jonathan H.
and Vallanat, Beena and Ledbetter, Allen D. and Schladweiler, Mette
C. and Richards, Judy H. and Gottipolu, Reddy R. and Nyska, Abraham
and Kodavanti, Urmila P.},
title = {Subchronic inhalation of zinc sulfate induces cardiac changes in
healthy rats},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {232},
pages = {69--77},
number = {1},
month = oct,
abstract = {Zinc is a common metal in most ambient particulate matter (PM), and
has been proposed to be a causative component in PM-induced adverse
cardiovascular health effects. Zinc is also an essential metal and
has the potential to induce many physiological and nonphysiological
changes. Most toxicological studies employ high levels of zinc. We
hypothesized that subchronic inhalation of environmentally relevant
levels of zinc would cause cardiac changes in healthy rats. To address
this, healthy male WKY rats (12 weeks age) were exposed via nose
only inhalation to filtered air or 10, 30 or 100 [mu]g/m3 of aerosolized
zinc sulfate (ZnSO4), 5 h/day, 3 days/week for 16 weeks. Necropsies
occurred 48 h after the last exposure to ensure effects were due
to chronic exposure rather than the last exposure. No significant
changes were observed in neutrophil or macrophage count, total lavageable
cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl
[beta]-d-glucosaminidase, [gamma]-glutamyl transferase) in bronchoalveolar
lavage fluid, indicating minimal pulmonary effect. In the heart,
cytosolic glutathione peroxidase activity decreased, while mitochondrial
ferritin levels increased and succinate dehydrogenase activity decreased,
suggesting a mitochondria-specific effect. Although no cardiac pathology
was seen, cardiac gene array analysis indicated small changes in
genes involved in cell signaling, a pattern concordant with known
zinc effects. These data indicate that inhalation of zinc at environmentally
relevant levels induces cardiac effects. While changes are small
in healthy rats, these may be especially relevant in individuals
with pre-existent cardiovascular disease.},
issn = {0041-008X},
keywords = {Zinc, Particulate matter, Cardiovascular injury},
url = {http://www.sciencedirect.com/science/article/B6WXH-4SP3SM6-1/2/beb816286af407724fb3bb897cbc13df}
}
@ARTICLE{Walley2010,
author = {Walley, Justin W. and Kelley, Dior R. and Nestorova, Gergana and
Hirschberg, David L. and Dehesh, Katayoon},
title = {Arabidopsis Deadenylases AtCAF1a and AtCAF1b Play Overlapping and
Distinct Roles in Mediating Environmental Stress Responses},
journal = {Plant Physiology},
year = {2010},
volume = {152},
pages = {866--875},
number = {2},
month = feb,
abstract = {To maintain homeostasis in an ever-changing environment organisms
have evolved mechanisms to reprogram gene expression. One central
mechanism regulating gene expression is messenger RNA (mRNA) degradation,
which is initiated by poly(A) tail shortening (deadenylation). The
carbon catabolite repressor 4-CCR4 associated factor1 (CCR4-CAF1)
complex is the major enzyme complex that catalyzes mRNA deadenylation
and is conserved among eukaryotes. However, the components and functions
of this global regulatory complex have not been well characterized
in plants. Here we investigate the CAF1 family in Arabidopsis (Arabidopsis
thaliana). We identify 11 AtCAF1 homologs and show that a subset
of these genes are responsive to mechanical wounding, among them
are AtCAF1a and AtCAF1b whose expression levels are rapidly and transiently
induced by wounding. The differential expression profiles of the
various AtCAF1s suggest that not all AtCAF1 genes are involved in
stress-responsive regulation of transcript levels. Comparison of
misexpressed genes identified via transcript profiling of Atcaf1a
and Atcaf1b mutants at different time points before and after wounding
suggests that AtCAF1a and AtCAF1b target shared and unique transcripts
for deadenylation with temporal specificity. Consistent with the
AtPI4K{gamma}3 transcript exhibiting the largest increase in abundance
in Atcaf1b, AtCAF1b targets AtPI4K{gamma}3 mRNA for deadenylation.
Stress-tolerance assays demonstrate that AtCAF1a and AtCAF1b are
involved in mediating abiotic stress responses. However, AtCAF1a
and AtCAF1b are not functionally redundant in all cases, nor are
they essential for all environmental stresses. These findings demonstrate
that these closely related proteins exhibit overlapping and distinct
roles with respect to mRNA deadenylation and mediation of stress
responses.},
url = {http://www.plantphysiol.org/cgi/content/abstract/152/2/866}
}
@ARTICLE{Walmsley2005,
author = {Walmsley, Sarah R. and Print, Cristin and Farahi, Neda and Peyssonnaux,
Carole and Johnson, Randall S. and Cramer, Thorsten and Sobolewski,
Anastasia and Condliffe, Alison M. and Cowburn, Andrew S. and Johnson,
Nicola and Chilvers, Edwin R.},
title = {Hypoxia-induced neutrophil survival is mediated by HIF-1{alpha}-dependent
NF-{kappa}B activity},
journal = {J. Exp. Med.},
year = {2005},
volume = {201},
pages = {105--115},
number = {1},
month = jan,
abstract = {Neutrophils are key effector cells of the innate immune response and
are required to migrate and function within adverse microenvironmental
conditions. These inflammatory sites are characterized by low levels
of oxygen and glucose and high levels of reductive metabolites. A
major regulator of neutrophil functional longevity is the ability
of these cells to undergo apoptosis. We examined the mechanism by
which hypoxia causes an inhibition of neutrophil apoptosis in human
and murine neutrophils. We show that neutrophils possess the hypoxia-inducible
factor (HIF)-1{alpha} and factor inhibiting HIF (FIH) hydroxylase
oxygen-sensing pathway and using HIF-1{alpha}-deficient myeloid cells
demonstrate that HIF-1{alpha} is directly involved in regulating
neutrophil survival in hypoxia. Gene array, TaqMan PCR, Western blotting,
and oligonucleotide binding assays identify NF-{kappa}B as a novel
hypoxia-regulated and HIF-dependent target, with inhibition of NF-{kappa}B
by gliotoxin or parthenolide resulting in the abrogation of hypoxic
survival. In addition, we identify macrophage inflammatory protein-1{beta}
as a novel hypoxia-induced neutrophil survival factor.},
url = {http://jem.rupress.org/cgi/content/abstract/201/1/105}
}
@ARTICLE{Walsh2008,
author = {Walsh, Christine S. and Ogawa, Seishi and Karahashi, Hisae and Scoles,
Daniel R. and Pavelka, James C. and Tran, Hang and Miller, Carl W.
and Kawamata, Norihiko and Ginther, Charles and Dering, Judy and
Sanada, Masashi and Nannya, Yasuhito and Slamon, Dennis J. and Koeffler,
H. Phillip and Karlan, Beth Y.},
title = {ERCC5 Is a Novel Biomarker of Ovarian Cancer Prognosis},
journal = {J. Clin. Oncol.},
year = {2008},
volume = {26},
pages = {2952--2958},
number = {18},
month = jun,
abstract = {PurposeTo identify a biomarker of ovarian cancer response to chemotherapy.
Patients and MethodsStudy participants had epithelial ovarian cancer
treated with surgery followed by platinum-based chemotherapy. DNA
and RNA were isolated from frozen tumors and normal DNA was isolated
from matched peripheral blood. A whole-genome loss of heterozygosity
(LOH) analysis was performed using a high-density oligonucleotide
array. Candidate genomic areas that predicted enhanced response to
chemotherapy were identified with Cox proportional hazards methods.
Gene expression analyses were performed through microarray experiments.
Candidate genes were tested for independent effects on survival using
Cox proportional hazards models, Kaplan-Meier survival curves, and
the log-rank test. ResultsUsing a whole-genome approach to study
the molecular determinants of ovarian cancer response to platinum-based
chemotherapy, we identified LOH of a 13q region to predict prolonged
progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5
was identified as a candidate gene in this region because of its
known function in the nucleotide excision repair pathway, the unique
DNA repair pathway that removes platinum-DNA adducts. We found LOH
of the ERCC5 gene locus and downregulation of ERCC5 gene expression
to predict prolonged PFS. Integration of genomic and gene expression
data shows a correlation between 13q LOH and ERCC5 gene downregulation.
ConclusionERCC5 is a novel biomarker of ovarian cancer prognosis
and a potential therapeutic target of ovarian cancer response to
platinum chemotherapy.},
url = {http://jco.ascopubs.org/cgi/content/abstract/26/18/2952}
}
@ARTICLE{Walsh2009,
author = {Walsh, Molly M. and Yi, Haiqing and Friedman, Julie and Cho, Kyoung-in
and Tserentsoodol, Nomingerel and McKinnon, Stuart and Searle, Kelly
and Yeh, Andrew and Ferreira, Paulo A.},
title = {Gene and Protein Expression Pilot Profiling and Biomarkers in an
Experimental Mouse Model of Hypertensive Glaucoma},
journal = {Exp Biol Med},
year = {2009},
volume = {234},
pages = {918--930},
number = {8},
month = aug,
abstract = {Glaucoma is a group of genetically heterogeneous neurodegenerative
disorders causing the degeneration of the ganglion neurons of the
retina. Increased intraocular pressure (IOP) is a hallmark risk factor
promoting the death of ganglion neurons of the retina in glaucoma.
Yet, the molecular processes underlying the degeneration of these
neurons by increased IOP are not understood. To gain insight into
the early molecular events and discover biomarkers induced by IOP,
we performed gene and protein expression profiling to compare retinas
of eyes with and without high IOP in a rodent model of experimental
glaucoma. This pilot study found that the IOP-mediated changes in
the transcription levels of a restricted set of genes implicated
in peroxisomal and mitochondrial function, modulation of neuron survival
and inflammatory processes, were also accompanied by changes in the
levels of proteins encoded by the same genes. With the exception
of the inflammatory markers, serum amyloid-A1 (SAA1) and serum amyloid-A2
(SAA2), the IOP-induced changes in protein expression were restricted
to ganglion neurons of the retina and they were detected also in
the vitreous, thus suggesting an early IOP-mediated loss of ganglion
cell integrity. Interestingly, SAA1 and SAA2 were induced in retinal
microglia cells, whereas they were reduced in sera of IOP-responsive
mice. Hence, this study defines novel IOP-induced molecular processes,
biomarkers and sources thereof, and it further validates the extension
of the analyses herein reported to other genes modulated by IOP.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/234/8/918}
}
@ARTICLE{Walsh2003,
author = {Walsh, Patrick J. and Bookman, Richard J. and Zaias, Julia and Mayer,
Gregory D. and Abraham, William and Bourdelais, Andrea J. and Baden,
Daniel G.},
title = {Toxicogenomic effects of marine brevetoxins in liver and brain of
mouse},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2003},
volume = {136},
pages = {173--182},
number = {2},
month = oct,
abstract = {Although the polyether brevetoxins (PbTx's) produced by Karenia brevis
(the organism responsible for blooms of the Florida red tide) are
known to exert their acute toxic effects through ion-channel mediated
pathways in neural tissue, prior studies have also demonstrated that
at least one form of the toxin (PbTx-6) is bound avidly by the aryl
hydrocarbon receptor (AhR). Since AhR binding of a prototypical ligand
such as dioxin is the first step in a cascade pathway producing major
changes in gene expression, we reasoned that PbTx-6 might produce
similar genomic-wide changes in expression. Mice were injected i.p.
with sub-lethal doses of PbTx's (either 1.5 or 3 mg/g body weight
of PbTx-6; or 0.15 mg/g body weight of PbTx-2, a toxin not avidly
bound by the AhR), and liver and brain tissues were sampled at 8,
24 and 72 h and RNA was isolated. Changes in gene-specific RNA levels
were assessed using commercially available mouse cDNA arrays (Incyte)
containing >9600 array elements, including many elements from AhR-mediated
genes. Histopathology of the two organs was also assessed. We observed
minor histopathological effects and a total of only 29 significant
(>2.0-fold) changes in gene expression, most of which occurred in
the liver, and most of which could be attributable to an [`]acute
phase' inflammatory response. These results argue against the hypothesis
that PbTx-6 acts via a classic AhR-mediated mechanism to evoke gene
expression changes. However, given the avidity with which PbTx-6
binds to the AhR, these findings have important implications for
how PbTx's may act in concert with other toxicants that are sensed
by the AhR.},
issn = {1096-4959},
keywords = {Marine brevetoxins, Toxic dinoflagellates, Karenia brevis, Toxicogenomics,
Gene arrays, Metallothioneins, Orosomucoid, Lethal shock},
url = {http://www.sciencedirect.com/science/article/B6T2R-49CMK45-4/2/3a4095272ca7e0f05ac29739bf7c379a}
}
@ARTICLE{Walter2010b,
author = {Walter, Isabel and Hegarty, Bronwyn and Seebacher, Frank},
title = {AMP-activated protein kinase controls metabolism and heat production
during embryonic development in birds},
journal = {J. Exp. Biol.},
year = {2010},
volume = {213},
pages = {3167--3176},
number = {18},
month = sep,
abstract = {During embryonic and early juvenile development, endotherms must balance
energy allocation between growth and heat production. Failure to
either match the ATP demand of growing tissue or produce heat at
the correct developmental stage will lead to damage of the organism.
We tested the hypothesis that AMP-activated protein kinase (AMPK)
is involved in the regulation of energy metabolism and heat production
during development in the chicken (Gallus gallus). We show that mRNA
concentrations of regulatory and catalytic AMPK subunits, AMPK total
protein, and AMPK phosphorylation increase during development [3
days (-3 days) and one day (-1 day) before hatching, and +1 day and
+8 days after hatching] in liver, and to a lesser extent in skeletal
muscle. Chronic stimulation with 5-aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside
(AICAR) significantly increases AMPK phosphorylation in skeletal
muscle and in liver. This increase was paralleled by significant
increases in heat production, glucose utilization, and liver and
skeletal muscle mitochondrial capacity (citrate synthase activity).
The effects of AMPK are likely to be mediated by inhibition of acetyl
CoA carboxylase (ACC) after hatching, when ACC protein concentration
increases significantly, and by a significant AMPK-induced increase
in PGC-1{alpha} mRNA concentration (at +1 day), but not in NRF-1
mRNA concentration. AMPK phosphorylation is under the control of
thyroid hormone, and AMPK phosphorylation decreases significantly
following the induction of hypothyroidism. We propose AMPK as a principal
regulatory mechanism during the transition from ectothermy to endothermy
in birds, and show that AMPK function in birds is similar to that
observed in mammals.},
url = {http://jeb.biologists.org/cgi/content/abstract/213/18/3167}
}
@ARTICLE{Walter2009,
author = {Walter, Isabel and Seebacher, Frank},
title = {Endothermy in birds: underlying molecular mechanisms},
journal = {J. Exp. Biol.},
year = {2009},
volume = {212},
pages = {2328--2336},
number = {15},
month = aug,
abstract = {Endothermy is significant in vertebrate evolution because it changes
the relations between animals and their environment. How endothermy
has evolved in archosaurs (birds, crocodiles and dinosaurs) is controversial
especially because birds do not possess brown adipose tissue, the
specialized endothermic tissue of mammals. Internal heat production
is facilitated by increased oxidative metabolic capacity, accompanied
by the uncoupling of aerobic metabolism from energy (ATP) production.
Here we show that the transition from an ectothermic to an endothermic
metabolic state in developing chicken embryos occurs by the interaction
between increased basal ATP demand (Na+/K+-ATPase activity and gene
expression), increased oxidative capacity and increased uncoupling
of mitochondria; this process is controlled by thyroid hormone via
its effect on PGC1{alpha} and adenine nucleotide translocase (ANT)
gene expression. Mitochondria become more uncoupled during development,
but unlike in mammals, avian uncoupling protein (avUCP) does not
uncouple electron transport from oxidative phosphorylation and therefore
plays no role in heat production. Instead, ANT is the principal uncoupling
protein in birds. The relationship between oxidative capacity and
uncoupling indicates that there is a continuum of phenotypes that
fall between the extremes of selection for increased heat production
and increased aerobic activity, whereas increased cellular ATP demand
is a prerequisite for increased oxidative capacity.},
url = {http://jeb.biologists.org/cgi/content/abstract/212/15/2328}
}
@ARTICLE{Walter2007,
author = {Walter, Isabel and Seebacher, Frank},
title = {Molecular mechanisms underlying the development of endothermy in
birds (Gallus gallus): a new role of PGC-1{alpha}?},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {293},
pages = {R2315--2322},
number = {6},
month = dec,
abstract = {In endotherms, plasticity of internal heat production in response
to environmental variability is an important component of thermoregulation.
During embryogenesis endotherms cannot regulate their body temperature
metabolically and are therefore similar to ectotherms. The transition
from ectothermy to endothermy occurs by the development of metabolic
capacity during embryogenesis. Here we test the hypothesis that the
development of metabolism during embryogenesis in birds is under
transcriptional control and that metabolic capacity is upregulated
in colder environments. The peroxisome proliferator-activated receptor-{gamma}
(PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) is the major metabolic
regulator in mammals. PGC-1{alpha} and its target PPAR{gamma} were
significantly elevated during development in pectoral muscle and
liver of chickens (Gallus gallus) compared with adults. However,
the timing of upregulation of PGC-1{alpha} and PPAR{gamma} was not
in synchrony. In cool incubation temperatures (35{degrees}C) both
PGC-1{alpha} and PPAR{gamma} gene expression was increased in liver
but not in skeletal muscle, compared with a 38{degrees}C incubation
treatment. Cytochrome c oxidase and citrate synthase enzyme activities
and ATP synthase gene expression increased during embryonic development
in liver and muscle, and there was a significant effect of incubation
temperature on these parameters. Our findings suggest that PGC-1{alpha}
might be important for establishing endothermic metabolic capacity
during embryogenesis in birds.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/293/6/R2315}
}
@ARTICLE{Walter2011,
author = {Walter, Martin A. and Benz, Matthias R. and Hildebrandt, Isabel J.
and Laing, Rachel E. and Hartung, Verena and Damoiseaux, Robert D.
and Bockisch, Andreas and Phelps, Michael E. and Czernin, Johannes
and Weber, Wolfgang A.},
title = {Metabolic Imaging Allows Early Prediction of Response to Vandetanib},
journal = {J. Nucl. Med.},
year = {2011},
volume = {52},
pages = {231--240},
number = {2},
month = feb,
abstract = {The RET (rearranged-during-transfection protein) protooncogene triggers
multiple intracellular signaling cascades regulating cell cycle progression
and cellular metabolism. We therefore hypothesized that metabolic
imaging could allow noninvasive detection of response to the RET
inhibitor vandetanib in vivo. Methods: The effects of vandetanib
treatment on the full-genome expression and the metabolic profile
were analyzed in the human medullary thyroid cancer cell line TT.
In vitro, transcriptional changes of pathways regulating cell cycle
progression and glucose, dopa, and thymidine metabolism were correlated
to the results of cell cycle analysis and the uptake of 3H-deoxyglucose,
3H-3,4-dihydroxy-L-phenylalanine, and 3H-thymidine under vandetanib
treatment. In vivo, the tumor metabolism under vandetanib was monitored
by small-animal PET of tumor-bearing mice. Results: Vandetanib treatment
resulted in the transcriptional downregulation of various effector
pathways with consecutive downregulation of cyclin expression and
a G0/G1 arrest. In vitro, vandetanib treatment resulted in the decreased
expression of genes regulating glucose, 3,4-dihydroxy-L-phenylalanine,
and thymidine metabolism, with a subsequent reduction in the functional
activity of the corresponding pathways. In vivo, metabolic imaging
with PET was able to assess changes in the tumoral glucose metabolism
profile as early as 3 d after initiation of vandetanib treatment.
Conclusion: We describe a metabolic imaging approach for the noninvasive
detection of successful vandetanib treatment. Our results suggest
that PET may be useful for identifying patients who respond to vandetanib
early in the course of treatment.},
comment = {10.2967/jnumed.110.081745},
url = {http://jnm.snmjournals.org/cgi/content/abstract/52/2/231}
}
@ARTICLE{Walter2010a,
author = {Walter, M. and Bonin, M. and Pullman, R. Saunders and Valente, E.M.
and Loi, M. and Gambarin, M. and Raymond, D. and Tinazzi, M. and
Kamm, C. and Glöckle, N. and Poths, S. and Gasser, T. and Bressman,
S.B. and Klein, C. and Ozelius, L.J. and Riess, O. and Grundmann,
K.},
title = {Expression profiling in peripheral blood reveals signature for penetrance
in DYT1 dystonia},
journal = {Neurobiology of Disease},
year = {2010},
volume = {38},
pages = {192--200},
number = {2},
month = may,
abstract = {DYT1 dystonia is an autosomal-dominantly inherited movement disorder,
which is usually caused by a GAG deletion in the TOR1A gene. Due
to the reduced penetrance of ~ 30-40%, the determination of the mutation
in a subject is of limited use with regard to actual manifestation
of symptoms. In the present study, we used Affymetrix oligonucleotide
microarrays to analyze global gene expression in blood samples of
15 manifesting and 15 non-manifesting mutation carriers in order
to identify a susceptibility profile beyond the GAG deletion which
is associated with the manifestation of symptoms in DYT1 dystonia.
We identified a genetic signature which distinguished between asymptomatic
mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity
and 100% specificity. This genetic signature could correctly predict
the disease state in an independent test set with a sensitivity of
87.5% and a specificity of 85.7%. Conclusively, this genetic signature
might provide a possibility to distinguish DYT1 patients from asymptomatic
mutation carriers.},
booktitle = {Neurobiology of developmental disorders involving human higher cognition},
issn = {0969-9961},
keywords = {DYT1 dystonia, Gene expression profiling, TorsinA, Penetrance},
url = {http://www.sciencedirect.com/science/article/B6WNK-4Y34V30-1/2/6ee461ffc29bfe4170138655de6002c7}
}
@ARTICLE{Walter2010,
author = {Walter, Michael and Piepenburg, Katrin and Schöttler, Mark Aurel
and Petersen, Kerstin and Kahlau, Sabine and Tiller, Nadine and Drechsel,
Oliver and Weingartner, Magdalena and Kudla, Jörg and Bock, Ralph},
title = {Knockout of the plastid RNase E leads to defective RNA processing
and chloroplast ribosome deficiency},
journal = {The Plant Journal},
year = {2010},
volume = {64},
pages = {851--863},
number = {5},
abstract = {Summary Ribonuclease E (RNase E) represents a key enzyme in bacterial
RNA metabolism. It plays multifarious roles in RNA processing and
also initiates degradation of mRNA by endonucleolytic cleavage. Plastids
(chloroplasts) are derived from formerly free-living bacteria and
have largely retained eubacterial gene expression mechanisms. Here
we report the functional characterization of a chloroplast RNase
E that is encoded by a single-copy nuclear gene in the model plant
Arabidopsis thaliana. Analysis of knockout plants revealed that,
unlike in bacteria, RNase E is not essential for survival. Absence
of RNase E results in multiple defects in chloroplast RNA metabolism.
Most importantly, polycistronic precursor transcripts overaccumulate
in the knockout plants, while several mature monocistronic mRNAs
are strongly reduced, suggesting an important function of RNase E
in intercistronic processing of primary transcripts from chloroplast
operons. We further show that disturbed maturation of a transcript
encoding essential ribosomal proteins results in plastid ribosome
deficiency and, therefore, provides a molecular explanation for the
observed mutant phenotype.},
doi = {10.1111/j.1365-313X.2010.04377.x},
issn = {1365-313X},
keywords = {plastid, RNase E, Arabidopsis thaliana, RNA processing, RNA stability,
RNA degradation, translation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04377.x}
}
@ARTICLE{Walter2004,
author = {Walter, Matthew J. and Park, John S. and Lau, Steven K. M. and Li,
Xia and Lane, Andrew A. and Nagarajan, Rakesh and Shannon, William
D. and Ley, Timothy J.},
title = {Expression Profiling of Murine Acute Promyelocytic Leukemia Cells
Reveals Multiple Model-Dependent Progression Signatures},
journal = {Mol. Cell. Biol.},
year = {2004},
volume = {24},
pages = {10882--10893},
number = {24},
month = dec,
abstract = {Leukemia results from the expansion of self-renewing hematopoietic
cells that are thought to contain mutations that contribute to disease
initiation and progression. Studies of the gene expression profiles
of human acute myeloid leukemia samples has allowed their classification
based on the presence of translocations and French-American-British
subtypes, but it is not yet clear whether their molecular signatures
reflect the initiating mutations or mutations acquired during progression.
To begin to address this question, we examined the expression profiles
of normal murine promyelocyte-enriched samples, nontransformed murine
promyelocytes expressing human promyelocytic leukemia-retinoic acid
receptor alpha (PML-RAR{alpha}) fusion gene, and primary acute promyelocytic
leukemia cells. The expression profile of nontransformed cells expressing
PML-RAR{alpha} was remarkably similar to that of wild-type promyelocytes.
In contrast, the expression profiles of fully transformed cells from
three acute promyelocytic leukemia model systems were all different,
suggesting that the expression signature of acute promyelocytic leukemia
cells reflects the genetic changes that contributed to progression.
To further evaluate these progression events, we compared two high-penetrance
acute promyelocytic leukemia models that both commonly acquire an
interstitial deletion of chromosome 2 during progression. The two
models exhibited distinct gene expression profiles, suggesting that
the dominant molecular signatures of murine acute promyelocytic leukemia
can be influenced by several independent progression events.},
url = {http://mcb.asm.org/cgi/content/abstract/24/24/10882}
}
@ARTICLE{Waltering2011,
author = {Waltering, Kati K. and Porkka, Kati P. and Jalava, Sanni E. and Urbanucci,
Alfonso and Kohonen, Pekka J. and Latonen, Leena M. and Kallioniemi,
Olli P. and Jenster, Guido and Visakorpi, Tapio},
title = {Androgen regulation of micro-RNAs in prostate cancer},
journal = {The Prostate},
year = {2011},
volume = {71},
pages = {604--614},
number = {6},
abstract = {Abstract BACKGROUNDAndrogens play a critical role in the growth of
both androgen dependent and castration-resistant prostate cancer
(CRPC). Only a few micro-RNAs (miRNAs) have been suggested to be
androgen regulated. We aim to identify androgen regulated miRNAs.METHODSWe
utilized LNCaP derived model, we have established, and which overexpresses
the androgen receptor (AR), the VCaP cell line, and 13 intact-castrated
prostate cancer (PC) xenograft pairs, as well as clinical specimens
of untreated (PC) and CRPC. The expression of miRNAs was analyzed
by microarrays and quantitative RT-PCR (Q-RT-PCR). Transfection of
pre-miR-141 and anti-miR-141 was also used.RESULTSSeventeen miRNAs
were >1.5-fold up- or downregulated upon dihydrotestosterone (DHT)
treatment in the cell lines, and 42 after castration in the AR-positive
xenografts. Only four miRNAs (miR-10a, miR-141, miR-150*, and miR-1225-5p)
showed similar androgen regulation in both cell lines and xenografts.
Of those, miR-141 was found to be expressed more in PC and CRPC compared
to benign prostate hyperplasia. Additionally, the overexpression
of miR-141 enhanced growth of parental LNCaP cells while inhibition
of miR-141 by anti-miR-141 suppressed the growth of the LNCaP subline
overexpressing AR.CONCLUSIONSOnly a few miRNAs were found to be androgen-regulated
in both cell lines and xenografts models. Of those, the expression
of miR-141 was upregulated in cancer. The ectopic overexpression
of miR-141 increased growth of LNCaP cell suggesting it may contribute
to the progression of PC. Prostate 71:604–614, 2011. © 2010 Wiley-Liss,
Inc.},
doi = {10.1002/pros.21276},
issn = {1097-0045},
keywords = {AR, prostatic carcinoma, neoplasia, hormone-refractory, LNCaP-ARhi},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.21276}
}
@ARTICLE{WALTERS2008,
author = {WALTERS, DENISE KATHERINE and STEINMANN, PATRICK and LANGSAM, BETTINA
and SCHMUTZ, SILVIA and BORN, WALTER and FUCHS, BRUNO},
title = {Identification of Potential Chemoresistance Genes in Osteosarcoma},
journal = {Anticancer Res},
year = {2008},
volume = {28},
pages = {673--679},
number = {2A},
month = mar,
abstract = {Background: Osteosarcoma (OS) is an aggressive bone malignancy that
primarily affects children and adolescents. Patients with metastatic
disease at diagnosis have only a 20% survival rate. The poor survival
rate of these patients is largely due to their lack of responsiveness
to chemotherapy. However, the mechanisms underlying osteosarcoma
chemoresistance remain unknown. Materials and Methods: The effect
of cisplatin, doxorubicin and etoposide was examined on OS cell lines.
Affymetric Genechip analysis was used to examine differential gene
expression. Results: A correlation between increasing metastatic
potential and increasing chemoresistance was observed in the MG-63
cell line and sub-line model. Microarray analysis of these cell lines
revealed the differential expression of several genes potentially
involved in chemoresistance including ABCG2, ADD3, NMT2, WNT5a and
PTN. Conclusion: The identification of genes contributing to chemoresistance
and determining the role these genes play is critical in characterizing
patient responsiveness and overcoming chemoresistance in osteosarcoma
patients.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/28/2A/673}
}
@ARTICLE{Walters2009,
author = {Walters, Emily and Rider, Virginia and Abdou, Nabih I. and Greenwell,
Cindy and Svojanovsky, Stan and Smith, Peter and Kimler, Bruce F.},
title = {Estradiol targets T cell signaling pathways in human systemic lupus},
journal = {Clinical Immunology},
year = {2009},
volume = {133},
pages = {428--436},
number = {3},
month = dec,
abstract = {The major risk factor for developing systemic lupus erythematosus
(SLE) is being female. The present study utilized gene profiles of
activated T cells from females with SLE and healthy controls to identify
signaling pathways uniquely regulated by estradiol that could contribute
to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol)
were measured by real time polymerase chain amplification. Estradiol
uniquely upregulated six pathways in SLE T cells that control T cell
function including interferon-[alpha] signaling. Measurement of interferon-[alpha]
pathway target gene expression revealed significant differences (p =
0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1
expression was bimodal and correlated moderately (r = 0.55) with
disease activity. The results indicate that estradiol alters signaling
pathways in activated SLE T cells that control T cell function. Differential
expression of transcriptional coactivators could influence estrogen-dependent
gene regulation in T cell signaling and contribute to SLE onset and
disease pathogenesis.},
issn = {1521-6616},
keywords = {SLE, Estradiol, Interferon-[alpha], T cell signaling, Microarray},
url = {http://www.sciencedirect.com/science/article/B6WCJ-4XBP98W-2/2/6425b4c08c21c7c29687242a8e3b149f}
}
@ARTICLE{Walters2006,
author = {Walters, Kathie-Anne and Smith, Maria W. and Pal, Sampa and Thompson,
Jill C. and Thomas, Matthew J. and Yeh, Matthew M. and Thomas, David
L. and Fitzgibbon, Matthew and Proll, Sean and Fausto, Nelson and
Gretch, David R. and Carithers Jr., Robert L. and Shuhart, Margaret
C. and Katze, Michael G.},
title = {Identification of a specific gene expression pattern associated with
HCV-induced pathogenesis in HCV- and HCV/HIV-infected individuals},
journal = {Virology},
year = {2006},
volume = {350},
pages = {453--464},
number = {2},
month = jul,
abstract = {Gene expression profiling was performed on liver biopsies from 28
patients (12 HCV and 16 HCV/HIV infected) in an attempt to understand
the mechanisms of HCV liver disease in the presence and absence of
HIV coinfection. The data were compared with clinical observations
and a gene expression database obtained for transplant HCV-infected
samples. This is the first report of functional genomics being used
to compare intrahepatic gene expression profiles of HCV- and HCV/HIV-infected
individuals. Significantly, the intrahepatic global gene expression
profiles do not differ between HCV- and HCV/HIV-infected individuals.
However, a subset of patients was identified who share a specific
pattern of gene expression, termed the enhanced gene expression (EGE)
pattern. Specifically, the EGE (+) patients show a dramatic decreased
expression of multiple genes associated with the FAS-apoptosis pathway
and increased expression of lymphocyte adhesion molecules and lymphocyte-specific
genes. The EGE (+) patients also have partially impaired Type I and
II IFN-mediated antiviral responses, including a lack of induction
of the anti-fibrogenic cytokine IFN-[gamma]. Importantly, the pattern
of gene expression observed in EGE (+) patients has similarities
to patients who developed fibrosis within 1 year of receiving a liver
transplant.},
issn = {0042-6822},
keywords = {Viral hepatitis, Apoptosis, Fibrosis, Interferon, Microarray},
url = {http://www.sciencedirect.com/science/article/B6WXR-4JKRTHW-1/2/6b5c0b0c071b62098090b63e43d13fbc}
}
@ARTICLE{Walton2006,
author = {Walton, Melanie J. and Bayne, Rosemary A. L. and Wallace, Ian and
Baird, David T. and Anderson, Richard A.},
title = {Direct Effect of Progestogen on Gene Expression in the Testis during
Gonadotropin Withdrawal and Early Suppression of Spermatogenesis},
journal = {J. Clin. Endocrinol. Metab.},
year = {2006},
volume = {91},
pages = {2526--2533},
number = {7},
month = jul,
abstract = {Context: Testicular production of steroids and gametes is under gonadotropin
support, but there is little information as to the molecular mechanisms
by which these are regulated in the human. The testicular response
to gonadotropin withdrawal is important for the development of effective
contraceptive methods. Objective: Our objective was investigation
of expression of genes in the normal human testis reflecting steroidogenesis,
Sertoli cell function, and spermatogenesis after short-term gonadotropin
withdrawal and the effects of activating testicular progesterone
receptors. Design and Setting: We conducted a randomized controlled
trial at a research institute. Patients: Thirty healthy men participated.
Interventions: Subjects were randomized to no treatment or gonadotropin
suppression by GnRH antagonist (cetrorelix) with testosterone (CT
group) or with additional administration of the gestogen desogestrel
(CTD group) for 4 wk before testicular biopsy. Gene expression was
quantified by RT-PCR. Results: Both treatment groups showed similar
suppression of gonadotropins and sperm production and markedly reduced
expression of steroidogenic enzymes. Addition of progestogen in the
CTD group resulted in reduced expression of 5{alpha}-reductase type
1 compared with both controls and the CT group. Inhibin-{alpha} and
the spermatocyte marker acrosin-binding protein were significantly
lower in the CTD but not CT groups, compared with controls, but did
not differ between treated groups. Men who showed greater falls in
sperm production also showed reduced expression of these three genes
but not of the spermatid marker protamine 1. Conclusions: These data
provide evidence for direct progestogenic effects on the testis and
highlight steroid 5{alpha}-reduction and disruption of spermiation
as important components of the testicular response to gonadotropin
withdrawal.},
url = {http://jcem.endojournals.org/cgi/content/abstract/91/7/2526}
}
@ARTICLE{Walton2009,
author = {Walton, Thomas J. and Li, Geng and McCulloch, Thomas A. and Seth,
Rashmi and Powe, Desmond G. and Bishop, Michael C. and Rees, Robert
C.},
title = {Quantitative RT-PCR analysis of estrogen receptor gene expression
in laser microdissected prostate cancer tissue},
journal = {Prostate},
year = {2009},
volume = {69},
pages = {810--819},
number = {8},
abstract = {Abstract 10.1002/pros.20929.abs BACKGROUND Real-time quantitative
RT-PCR analysis of laser microdissected tissue is considered the
most accurate technique for determining tissue gene expression. The
discovery of estrogen receptor beta (ERβ) has focussed renewed interest
on the role of estrogen receptors in prostate cancer, yet few studies
have utilized the technique to analyze estrogen receptor gene expression
in prostate cancer. METHODS Fresh tissue was obtained from 11 radical
prostatectomy specimens and from 6 patients with benign prostate
hyperplasia. Pure populations of benign and malignant prostate epithelium
were laser microdissected, followed by RNA isolation and electrophoresis.
Quantitative RT-PCR was performed using primers for androgen receptor
(AR), estrogen receptor beta (ERβ), estrogen receptor alpha (ERα),
progesterone receptor (PGR) and prostate specific antigen (PSA),
with normalization to two housekeeping genes. Differences in gene
expression were analyzed using the Mann–Whitney U-test. Correlation
coefficients were analyzed using Spearman's test. RESULTS Significant
positive correlations were seen when AR and AR-dependent PSA, and
ERα and ERα-dependent PGR were compared, indicating a representative
population of RNA transcripts. ERβ gene expression was significantly
over-expressed in the cancer group compared with benign controls
(P < 0.01). In contrast, PGR expression was significantly down-regulated
in the cancer group (P < 0.05). There were no significant differences
in AR, ERα or PSA expression between the groups. This study represents
the first to show an upregulation of ERβ gene expression in laser
microdissected prostate cancer specimens. CONCLUSIONS In concert
with recent studies the findings suggest differential production
of ERβ splice variants, which may play important roles in the genesis
of prostate cancer. Prostate 69: 810–819, 2009. © 2009 Wiley-Liss,
Inc.},
issn = {1097-0045},
keywords = {estrogen receptor, gene expression, methodology, prostate cancer},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20929}
}
@ARTICLE{Walz2007,
author = {Walz, Markus and Kellermann, Sabine and Bylaite, Matilda and Andrée,
Birgit and Rüther, Ulrich and Paus, Ralf and Kloepper, Jennifer
E. and Reifenberger, Julia and Ruzicka, Thomas},
title = {Expression of the human Cathepsin L inhibitor hurpin in mice: skin
alterations and increased carcinogenesis},
journal = {Experimental Dermatology},
year = {2007},
volume = {16},
pages = {715--723},
number = {9},
abstract = {Abstract:  The serine protease inhibitor (serpin) hurpin (serpin
B13) is a cross class-specific inhibitor of the cysteine protease
Cathepsin (Cat) L. Cat L is involved in lysosomal protein degradation,
hair follicle morphogenesis, epidermal differentiation and epitope
generation of antigens. Hurpin is a 44Â kDa protein which is expressed
predominantly in epidermal cells. In psoriatic skin samples, hurpin
was strongly overexpressed when compared with normal skin. Keratinocytes
overexpressing hurpin showed increased resistance towards UVB-induced
apoptosis. To further analyse the functional importance of this inhibitor,
we have generated transgenic mice with deregulated Cat L activity
by expressing human hurpin in addition to the endogenous mouse inhibitor.
The three independent transgenic lines generated were characterized
by identical effects excluding insertional phenotypes. Macroscopically,
mice expressing human hurpin are characterized by abnormal abdominal
fur. The number of apoptotic cells and caspase-3 positive cells was
reduced after UV-irradiation in transgenic animals compared with
wild-type mice. Interestingly, after chemical carcinogenesis, transgenic
mice showed an increased susceptibility to develop skin cancer. Array
analysis of gene expression revealed distinct differences between
wild-type and hurpin-transgenic mice. Among others, differentially
expressed genes are related to antigen presentation and angiogenesis.
These results suggest an important role of Cat L regulation by hurpin
which might be of clinical relevance in human skin diseases.},
issn = {1600-0625},
keywords = {array analysis, cathepsin L inhibitor, hurpin, skin cancer, transgenic
mice},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0625.2007.00579.x}
}
@ARTICLE{Wamelen2011,
author = {van Wamelen, Daniel J. and Shan, Ling and Aziz, N. Ahmad and Anink,
Jasper J. and Bao, Ai-Min and Roos, Raymund A. C. and Swaab, Dick
F.},
title = {Functional Increase of Brain Histaminergic Signaling in Huntington's
Disease},
journal = {Brain Pathology},
year = {2011},
volume = {21},
pages = {419--427},
number = {4},
abstract = {To evaluate whether central histaminergic signaling in Huntington's
disease (HD) patients is affected, we assessed mRNA levels of histidine
decarboxylase (HDC), volume of and neuron number in the hypothalamic
tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In
addition, we assessed histamine N-methyltransferase (HMT) and histamine
receptor (H1R, H2R and H3R) mRNA levels in the inferior frontal gyrus
(IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by
real-time polymerase chain reaction. In HD patients, TMN volume and
neuronal number was unaltered (PÂ =Â 0.72, PÂ =Â 0.25). The levels
of HDC mRNA (PÂ =Â 0.046), IFG HMT (PÂ <Â 0.001), H1R (PÂ <Â 0.001)
and H3R mRNA levels (PÂ =Â 0.011) were increased, while CN H2R and
H3R mRNA levels were decreased (PÂ =Â 0.041, PÂ =Â 0.009). In HD
patients, we observed a positive correlation between IFG H3R mRNA
levels and CAG repeat length (PÂ =Â 0.024) and negative correlations
between age at onset of disease and IFG HMT (PÂ =Â 0.015) and H1R
(PÂ =Â 0.021) mRNA levels. These findings indicate a functional increase
in brain histaminergic signaling in HD, and provide a rationale for
the use of histamine receptor antagonists.},
doi = {10.1111/j.1750-3639.2010.00465.x},
issn = {1750-3639},
keywords = {histamine, histamine receptors, Huntington's disease, hypothalamus,
in situ hybridization, post-mortem},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2010.00465.x}
}
@ARTICLE{Wamunyokoli2006,
author = {Wamunyokoli, Fred W. and Bonome, Tomas and Lee, Ji-Young and Feltmate,
Colleen M. and Welch, William R. and Radonovich, Mike and Pise-Masison,
Cindy and Brady, John and Hao, Ke and Berkowitz, Ross S. and Mok,
Samuel and Birrer, Michael J.},
title = {Expression Profiling of Mucinous Tumors of the Ovary Identifies Genes
of Clinicopathologic Importance},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {690--700},
number = {3},
month = feb,
abstract = {Purpose: To elucidate the molecular mechanisms contributing to the
unique clinicopathologic characteristics of mucinous ovarian carcinoma,
global gene expression profiling of mucinous ovarian tumors was carried
out. Experimental Design: Gene expression profiling was completed
for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant
potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133
Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and
binary tree prediction analysis were used to determine the relationships
among mucinous specimens and a series of previously profiled microdissected
serous tumors and normal ovarian surface epithelium. PathwayAssist
software was used to identify putative signaling pathways involved
in the development of mucinous LMP tumors and adenocarcinomas. Results:
Comparison of the gene profiles between mucinous tumors and normal
ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially
expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas,
respectively. Hierarchical clustering showed that mucinous and serous
LMP tumors are distinct. In addition, there was a close association
of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas.
Binary tree prediction revealed increased heterogeneity among mucinous
tumors compared with their serous counterparts. Furthermore, the
cystadenomas coexpressed a subset of genes that were differentially
regulated in LMP and adenocarcinoma specimens compared with normal
ovarian surface epithelium. PathwayAssist highlighted pathways with
expression of genes involved in drug resistance in both LMP and adenocarcinoma
samples. In addition, genes involved in cytoskeletal regulation were
specifically up-regulated in the mucinous adenocarcinomas. Conclusions:
These data provide a useful basis for understanding the molecular
events leading to the development and progression of mucinous ovarian
cancer.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/3/690}
}
@ARTICLE{Wan2008,
author = {Wan, Fang and Miao, Xijiang and Quraishi, Iram and Kennedy, Valerie
and Creek, Kim E. and Pirisi, Lucia},
title = {Gene expression changes during HPV-mediated carcinogenesis: A comparison
between an in vitro cell model and cervical cancer},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {32--40},
number = {1},
abstract = {Abstract 10.1002/ijc.23463.abs We used oligonucleotide microarrays
to investigate gene expression changes associated with multi-step
human papillomavirus type 16 (HPV16)-mediated carcinogenesis in vitro.
Gene expression profiles in 4 early passage HPV16-immortalized human
keratinocyte (HKc) lines derived from different donors were compared
with their corresponding 4 late-passage, differentiation-resistant
cell lines, and to 4 pools of normal HKc, each composed of 3 individual
HKc strains, on Agilent 22 k human oligonucleotide microarrays. The
resulting data were analyzed using a modified T-test coded in R to
obtain lists of differentially expressed genes. Gene expression changes
identified in this model system were then compared with gene expression
changes described in published studies of cervical intraepithelial
neoplasia (CIN) and cervical cancer. Common genes in these lists
were further studied by cluster analysis. Genes whose expression
changed in the same direction as in CIN or cervical cancer (concordant)
at late stages of HPV16-mediated transformation in vitro formed one
major cluster, while those that changed in the opposite direction
(discordant) formed a second major cluster. Further annotation found
that many discordant expression changes involved gene products with
an extracellular localization. Two novel genes were selected for
further study: overexpression of SIX1 and GDF15, observed during
in vitro progression in our model system, was confirmed in tissue
arrays of cervical cancer. These microarray-based studies show that
our in vitro model system reflects many cellular and molecular alterations
characteristic of cervical cancer, and identified SIX1 and GDF15
as 2 novel potential biomarkers of cervical cancer progression. ©
2008 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {HPV, papillomavirus, cervical cancer, microarray, in vitro model},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23463}
}
@ARTICLE{Wan2008a,
author = {Wan, Fen and Zhang, Jun and Lau, Angela and Tan, Sarah and Burger,
Christian and Chu, Benjamin},
title = {Nanostructured copolymer gels for dsDNA separation by CE},
journal = {ELECTROPHORESIS},
year = {2008},
volume = {29},
pages = {4704--4713},
number = {23},
abstract = {Abstract 10.1002/elps.200800267.abs Pluronics are triblock copolymers
of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
that are able to form many different ordered nanostructures at appropriate
polymer concentrations and temperatures in selective solvents. These
nanostructured “gels� showed desirable criteria when used as
DNA separation media, especially in microchip electrophoresis, including
dynamic coating and viscosity switching. A ternary system of F127
(E99P69E99)/TBE buffer/1-butanol was selected as a model system to
test the sieving performance of different nanostructures in separating
dsDNA by CE. The nanostructures and their lattice constants were
determined by small-angle X-ray scattering. Viscosity measurements
showed the sol–gel transition phenomena. In addition to the cubic
structure, successful electrophoretic separation of dsDNA in 2-D
hexagonally packed cylinders was achieved. Results showed that without
further optimization, ΦX174 DNA–Hae III digest was well separated
within 15 min in a 7-cm separation channel, by using F127/TBE/1-butanol
gel with a 2-D hexagonal structure. A mechanism for DNA separations
by those gels with both hydrophilic and hydrophobic domains is discussed.},
issn = {1522-2683},
keywords = {2-D hexagonal, DNA separation, Nanostructures, Pluronics},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200800267}
}
@ARTICLE{Wan2010,
author = {Wan, Guoqiang and Yang, Kai and Lim, Qing [`]En and Zhou, Lihan and
He, Bei Ping and Wong, Hee Kit and Too, Heng-Phon},
title = {Identification and validation of reference genes for expression studies
in a rat model of neuropathic pain},
journal = {Biochemical and Biophysical Research Communications},
year = {2010},
volume = {400},
pages = {575--580},
number = {4},
month = oct,
abstract = {Neuropathic pain is triggered by damage to or as a result of the dysfunction
of the somatosensory nervous system. Gene expression profiling using
DNA microarray and real-time PCR have emerged as powerful tools for
the elucidation of pain-specific pathways and identification of candidate
biomarkers and therapeutic targets. Proper normalization of the gene
expression data with stable reference genes is a prerequisite to
obtaining accurate gene expression changes. We have evaluated the
stability of six candidate reference genes which include three commonly
used housekeeping genes (ACTB, GAPDH and HMBS) and three ribosomal
protein genes (RPL3, RPL19 and RPL29) using real-time PCR in a rat
model of neuropathic pain. Unexpectedly, ACTB but not GAPDH was stably
expressed. In addition, we have identified RPL29 and RPL3 as novel
reference genes. Normalization of expression data using GAPDH or
HMBS led to overestimation of transcriptional changes. Using RPL29/RPL3/ACTB
as reference genes, a number of transcripts were found to be specifically
and significantly regulated in injured dorsal root ganglia. These
genes may contribute to the development of neuropathic pain pathology
and may serve as candidate biomarkers for potential diagnosis.},
issn = {0006-291X},
keywords = {Reference genes, Neuropathic pain, Nerve root compression, Dorsal
root ganglia, Ribosomal protein genes, Housekeeping genes},
url = {http://www.sciencedirect.com/science/article/B6WBK-50X2NBT-7/2/6381339583906a26301b2ec6c12c0b58}
}
@ARTICLE{Wan2010a,
author = {Wan, H. and Seth, A. and Rainen, L. and Fernandes, H.},
title = {Coamplification of HIV-1 Proviral DNA and Viral RNA in Assays Used
for Quantification of HIV-1 RNA},
journal = {J. Clin. Microbiol.},
year = {2010},
volume = {48},
pages = {2186--2190},
number = {6},
month = jun,
abstract = {Elevated HIV-1 viral load (VL) observed in specimens frozen in situ
in plasma preparation tubes (PPTs) compared to EDTA plasma specimens
may affect therapeutic monitoring of HIV-infected patients. The increase
in viral load is cell associated and minimized when plasma from the
PPT is aspirated or recentrifuged prior to freezing. This study investigates
the contribution of integrated HIV-1 proviral DNA to elevated VL
in the quantification of HIV-1 RNA in plasma. Fifty paired specimens
collected in EDTA tubes and PPTs frozen in situ were used for analysis.
HIV-1 VL was measured using the COBAS Amplicor Monitor ultrasensitive
test version 1.5. Contaminating proviral DNA was detected using a
nested PCR targeting the Alu repeat in human genomic DNA and HIV
pol gene simultaneously. Treatment of the specimen with DNase resulted
in significantly lower quantifiable HIV-1 RNA in specimens from PPTs
compared to the corresponding EDTA tubes (P = 0.004). After the RNA
was destroyed by heat treatment, the mean HIV-1 RNA VL decreased
by 79% in the EDTA tube compared to 65% in the PPT. The nested PCR
amplified integrated proviral DNA in nucleic acid extracted from
plasma in PPT and EDTA specimens with high viral load values. Likewise,
a semiquantitative densitometric analysis revealed that the total
amount of genomic DNA in the PPT was higher than that in the EDTA
tube. Our investigation clearly shows that both proviral DNA and
intracellular RNA are amplified simultaneously in the COBAS Amplicor
HIV-1 Monitor assay and that proviral DNA contributes to the elevated
VL in plasma frozen in PPTs.},
url = {http://jcm.asm.org/cgi/content/abstract/48/6/2186}
}
@ARTICLE{Wan2007,
author = {Wan, Jian-Xin and Fukuda, Noboru and Endo, Morito and Tahira, Yoshiko
and Yao, En-Hui and Matsuda, Hiroyuki and Ueno, Takahiro and Matsumoto,
Koichi},
title = {Complement 3 is involved in changing the phenotype of human glomerular
mesangial cells},
journal = {J. Cell. Physiol.},
year = {2007},
volume = {213},
pages = {495--501},
number = {2},
abstract = {Abstract 10.1002/jcp.21129.abs Complement activation contributes to
tissue injury in various forms of glomerulopathy and is characterized
by deposition of complement components, which accelerates the progression
of chronic renal damage. We recently reported that complement 3 (C3),
a critical component of the complement system, is associated with
the synthetic phenotype of vascular smooth muscle cells. It is possible
that C3 stimulates mesangial cells to assume the synthetic phenotype
to, in turn, induce glomerular injury and sclerosis. We investigated
the role of C3 in the growth and phenotype of mesangial cells. Cultured
human mesangial cells (HMCs) expressed C3 mRNA and protein, and levels
were increased in response to IFN-γ and TNF-α. HMCs also expressed
C3a receptor mRNA and protein. Exogenous C3a stimulated DNA synthesis
in HMCs in a dose-dependent manner. C3a decreased expression h-caldesmon
mRNA, a marker of the contractile phenotype, and increased the expression
of osteopontin, matrix Gla, and collagen type1 α1 (collagen IV)
mRNAs, which are markers of the synthetic phenotype. C3a decreased
expression of α-smooth muscle actin in HMCs. Small interfering RNA
(siRNA) targeting C3 reduced the DNA synthesis and proliferation
of HMCs, increased expression of h-caldesmon mRNA, and decreased
expression of osteopontin, matrix Gla, and collagen IV mRNAs in HMCs.
These results indicate that C3 causes HMCs to convert to the synthetic
phenotype and stimulates growth of mesangial cells, suggesting that
C3 may play an important role in phenotypic regulation of mesangial
cells in renal diseases. J. Cell. Physiol. 213: 495–501, 2007.
© 2007 Wiley-Liss, Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.21129}
}
@ARTICLE{Wan2011,
author = {Yakun Wan and Weiming Chen and Jie Xing and Jinyin Tan and Bing Li
and Huiying Chen and Zhanxian Lin and Jung-Hsien Chiang and Saleem
Ramsey},
title = {Transcriptome profiling reveals a novel role for trichostatin A in
antagonizing histone chaperone Chz1 mediated telomere anti-silencing},
journal = {FEBS Letters},
year = {2011},
volume = {585},
pages = {2519 - 2525},
number = {15},
abstract = {The histone chaperones play an important role in chromatin assembly
and disassembly during replication and transcription. We have assessed
the global roles of histone chaperones in Saccharomyces cerevisiae.
Microarray transcriptional analyzes indicate that histone chaperones
have their own specific target genes, and various histone chaperones
have partially overlapping functions during transcriptional regulation.
The histone deacetylase inhibitor TSA and histone chaperones Asf1,
Vps75 and Rtt106 can function in parallel pathways to regulate transcription.
Moreover, TSA can specifically antagonize histone chaperone Chz1-mediated
telomere anti-silencing. This study demonstrates that a mutual cross-talk
mechanism exists between histone chaperones and histone deacetylation
in transcriptional regulation.},
doi = {10.1016/j.febslet.2011.06.036},
issn = {0014-5793},
keywords = {Histone chaperone},
url = {http://www.sciencedirect.com/science/article/pii/S0014579311005126}
}
@ARTICLE{Wan2008b,
author = {Wan, Yongfang and Poole, Rebecca and Huttly, Alison and Toscano-Underwood,
Claudia and Feeney, Kevin and Welham, Sue and Gooding, Mike and Mills,
Clare and Edwards, Keith and Shewry, Peter and Mitchell, Rowan},
title = {Transcriptome analysis of grain development in hexaploid wheat},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {121},
number = {1},
abstract = {BACKGROUND:Hexaploid wheat is one of the most important cereal crops
for human nutrition. Molecular understanding of the biology of the
developing grain will assist the improvement of yield and quality
traits for different environments. High quality transcriptomics is
a powerful method to increase this understanding.RESULTS:The transcriptome
of developing caryopses from hexaploid wheat (Triticum aestivum,
cv. Hereward) was determined using Affymetrix wheat GeneChip® oligonucleotide
arrays which have probes for 55,052 transcripts. Of these, 14,550
showed significant differential regulation in the period between
6 and 42 days after anthesis (daa). Large changes in transcript abundance
were observed which were categorised into distinct phases of differentiation
(6–10 daa), grain fill (12–21 daa) and desiccation/maturation (28–42
daa) and were associated with specific tissues and processes. A similar
experiment on developing caryopses grown with dry and/or hot environmental
treatments was also analysed, using the profiles established in the
first experiment to show that most environmental treatment effects
on transcription were due to acceleration of development, but that
a few transcripts were specifically affected. Transcript abundance
profiles in both experiments for nine selected known and putative
wheat transcription factors were independently confirmed by real
time RT-PCR. These expression profiles confirm or extend our knowledge
of the roles of the known transcription factors and suggest roles
for the unknown ones.CONCLUSION:This transcriptome data will provide
a valuable resource for molecular studies on wheat grain. It has
been demonstrated how it can be used to distinguish general developmental
shifts from specific effects of treatments on gene expression and
to diagnose the probable tissue specificity and role of transcription
factors.},
doi = {10.1186/1471-2164-9-121},
issn = {1471-2164},
pubmedid = {18325108},
url = {http://www.biomedcentral.com/1471-2164/9/121}
}
@ARTICLE{Wang2010e,
author = {Wang, Bin and Guo, Guangwu and Wang, Chao and Lin, Ying and Wang,
Xiaoning and Zhao, Mouming and Guo, Yong and He, Minghui and Zhang,
Yong and Pan, Li},
title = {Survey of the transcriptome of Aspergillus oryzae via massively parallel
mRNA sequencing},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {5075--5087},
number = {15},
month = aug,
abstract = {Aspergillus oryzae, an important filamentous fungus used in food fermentation
and the enzyme industry, has been shown through genome sequencing
and various other tools to have prominent features in its genomic
composition. However, the functional complexity of the A. oryzae
transcriptome has not yet been fully elucidated. Here, we applied
direct high-throughput paired-end RNA-sequencing (RNA-Seq) to the
transcriptome of A. oryzae under four different culture conditions.
With the high resolution and sensitivity afforded by RNA-Seq, we
were able to identify a substantial number of novel transcripts,
new exons, untranslated regions, alternative upstream initiation
codons and upstream open reading frames, which provide remarkable
insight into the A. oryzae transcriptome. We were also able to assess
the alternative mRNA isoforms in A. oryzae and found a large number
of genes undergoing alternative splicing. Many genes and pathways
that might be involved in higher levels of protein production in
solid-state culture than in liquid culture were identified by comparing
gene expression levels between different cultures. Our analysis indicated
that the transcriptome of A. oryzae is much more complex than previously
anticipated, and these results may provide a blueprint for further
study of the A. oryzae transcriptome.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/15/5075}
}
@ARTICLE{Wang2009,
author = {Wang, Bei and Han, Shuhong and Lien, Lily and Chang, Lung-Ji},
title = {Lentiviral calnexin-modified dendritic cells promote expansion of
high-avidity effector T cells with central memory phenotype},
journal = {Immunology},
year = {2009},
volume = {128},
pages = {43--57},
number = {1},
abstract = {Summary Dendritic cells (DCs) are key immune mediators for the education
and activation of effector cytotoxic T lymphocytes (CTLs). Ex vivo
manipulation of DCs is an attractive strategy in immunotherapy. The
chaperone proteins are known to hold the keys to proper protein folding
and antigen processing. However, little is known of the role of molecular
chaperones in DC and T-cell functions. We report that DCs expressing
supraphysiological levels of calnexin, a chaperone protein, via lentiviral
gene transfer stimulated the expansion of high-avidity CTLs with
increased central memory phenotype. Microarray RNA profiling and
analyses of protein expression with flow cytometry and multiplex
enzyme-linked immunosorbent assay indicated that calnexin had a global
effect on DCs with up-regulation of immune modulatory signals including
costimulatory molecules, cytokines, chemokines and adhesion molecules.
Compared with unmodified DCs, calnexin-DCs were capable of activating
T cells to exhibit increased functional avidity associated with up-regulation
of CCR7 and costimulatory tumour necrosis factor receptor superfamily
molecules. These findings demonstrate a prominent role of calnexin
in optimizing DC immunity with potential for improving immunotherapy.},
issn = {1365-2567},
keywords = {antigen presentation, calnexin, cytotoxic T cells, dendritic cells,
immunotherapy},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2009.03067.x}
}
@ARTICLE{Wang2011c,
author = {Wang, Beatrice T. and Ducker, Gregory S. and Barczak, Andrea J. and
Barbeau, Rebecca and Erle, David J. and Shokat, Kevan M.},
title = {The mammalian target of rapamycin regulates cholesterol biosynthetic
gene expression and exhibits a rapamycin-resistant transcriptional
profile},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {15201-15206},
number = {37},
abstract = {The mammalian target of rapamycin (mTOR) is a central regulator of
cell growth and proliferation in response to growth factor and nutrient
signaling. Consequently, this kinase is implicated in metabolic diseases
including cancer and diabetes, so there is great interest in understanding
the complete spectrum of mTOR-regulated networks. mTOR exists in
two functionally distinct complexes, mTORC1 and mTORC2, and whereas
the natural product rapamycin inhibits only a subset of mTORC1 functions,
recently developed ATP-competitive mTOR inhibitors have revealed
new roles for both complexes. A number of studies have highlighted
mTORC1 as a regulator of lipid homeostasis. We show that the ATP-competitive
inhibitor PP242, but not rapamycin, significantly down-regulates
cholesterol biosynthesis genes in a 4E-BP1-dependent manner in NIH
3T3 cells, whereas S6 kinase 1 is the dominant regulator in hepatocellular
carcinoma cells. To identify other rapamycin-resistant transcriptional
outputs of mTOR, we compared the expression profiles of NIH 3T3 cells
treated with rapamycin versus PP242. PP242 caused 1,666 genes to
be differentially expressed whereas rapamycin affected only 88 genes.
Our analysis provides a genomewide view of the transcriptional outputs
of mTOR signaling that are insensitive to rapamycin.},
doi = {10.1073/pnas.1103746108},
eprint = {http://www.pnas.org/cgi/reprint/108/37/15201.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/37/15201}
}
@ARTICLE{Wang2009a,
author = {Wang, Bing-yan and Wu, Jie and Lamont, Richard J. and Lin, Xinghua
and Xie, Hua},
title = {Negative Correlation of Distributions of Streptococcus cristatus
and Porphyromonas gingivalis in Subgingival Plaque},
journal = {J. Clin. Microbiol.},
year = {2009},
volume = {47},
pages = {3902--3906},
number = {12},
month = dec,
abstract = {Porphyromonas gingivalis is one of the major causative agents of adult
periodontitis. One of the features of this periodontal pathogen is
its ability to attach to a variety of oral bacterial surfaces and
to colonize subgingival dental plaque. We have shown that Streptococcus
cristatus CC5A inhibits expression of fimA, a gene encoding the major
protein subunit of long fimbriae in P. gingivalis; as a result, S.
cristatus interrupts formation of P. gingivalis biofilms. Here we
further demonstrate that the inhibitory activity of S. cristatus
affects multiple strains of P. gingivalis and that optimal inhibitory
activity correlates with levels of arginine deiminase expression
in S. cristatus. More strikingly, the impact of S. cristatus on P.
gingivalis colonization was revealed by comparing levels of P. gingivalis
and S. cristatus in subgingival dental plaque. Spearman correlation
analysis indicated a negative correlation between the distributions
of S. cristatus and P. gingivalis (r = -0.57; P < 0.05). These data
suggest that some early colonizers of dental plaque, such as S. cristatus,
may be beneficial to the host by antagonizing the colonization and
accumulation of periodontal pathogens such as P. gingivalis.},
url = {http://jcm.asm.org/cgi/content/abstract/47/12/3902}
}
@ARTICLE{Wang2005,
author = {Wang, Charles and Chelly, Marjorie R. and Chai, NingNing and Tan,
Yongxi and Hui, Thomas and Li, Hongmei and Farkas, Daniel L. and
Demetriou, Achilles A.},
title = {Transcriptomic fingerprinting of bone marrow-derived hepatic [beta]2m-/Thy-1+
stem cells},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {327},
pages = {252--260},
number = {1},
month = feb,
abstract = {The aim of the present study was to determine if the bone marrow (BM)
[beta]2m-/Thy-1+ stem cells isolated from common bile duct ligated
(CBDL) rats possess hepatocyte-like characteristics in their global
gene expression profiles. The Affymetrix RG U34A arrays were used
to conduct transcriptomic profiling on BM [beta]2m-/Thy-1+ stem cells
isolated from CBDL and control rats as well as primary hepatocytes.
Forty-one probe sets were up-regulated more than 2-fold in CBDL-derived
[beta]2m-/Thy-1+ BM stem cells compared to control BM stem cells.
Twenty-seven probe sets were present in both CBDL-derived [beta]2m-/Thy-1+
BM stem cells and control hepatocytes but absent in control [beta]2m-/Thy-1+
BM stem cells, including Tcf1 and Dbp. Compared to the control [beta]2m-/Thy-1+
BM stem cells, CBDL-derived [beta]2m-/Thy-1+ BM stem cells shared
more commonly expressed genes with hepatocytes. Overall, CBDL-derived
[beta]2m-/Thy-1+ stem cells displayed a different transcriptomic
fingerprint compared with [beta]2m-/Thy-1+ BM stem cells isolated
from control rats; and CBDL-derived [beta]2m-/Thy-1+ stem cells started
to express some hepatocyte-like genes.},
issn = {0006-291X},
keywords = {Bone marrow-derived hepatic stem cells, DNA microarray, Transcriptomic
profiling},
url = {http://www.sciencedirect.com/science/article/B6WBK-4F14WBF-5/2/71bd029a9cb743ba8349b2fa55bddf1f}
}
@ARTICLE{Wang2011m,
author = {Wang, Dai and Zetterstrom, Caroline E. and Gabrielsen, Mads and Beckham,
Katherine S. H. and Tree, Jai J. and Macdonald, Sarah E. and Byron,
Olwyn and Mitchell, Tim J. and Gally, David L. and Herzyk, Pawel
and Mahajan, Arvind and Uvell, Hanna and Burchmore, Richard and Smith,
Brian O. and Elofsson, Mikael and Roe, Andrew J.},
title = {Identification of Bacterial Target Proteins for the Salicylidene
Acylhydrazide Class of Virulence-blocking Compounds},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {29922-29931},
number = {34},
abstract = {A class of anti-virulence compounds, the salicylidene acylhydrazides,
has been widely reported to block the function of the type three
secretion system of several Gram-negative pathogens by a previously
unknown mechanism. In this work we provide the first identification
of bacterial proteins that are targeted by this group of compounds.
We provide evidence that their mode of action is likely to result
from a synergistic effect arising from a perturbation of the function
of several conserved proteins. We also examine the contribution of
selected target proteins to the pathogenicity of Yersinia pseudotuberculosis
and to expression of virulence genes in Escherichia coli O157.},
doi = {10.1074/jbc.M111.233858},
eprint = {http://www.jbc.org/cgi/reprint/286/34/29922.pdf},
url = {http://www.jbc.org/cgi/content/abstract/286/34/29922}
}
@ARTICLE{Wang2010d,
author = {Wang, David B. and Dayton, Robert D. and Zweig, Richard M. and Klein,
Ronald L.},
title = {Transcriptome analysis of a tau overexpression model in rats implicates
an early pro-inflammatory response},
journal = {Experimental Neurology},
year = {2010},
volume = {224},
pages = {197--206},
number = {1},
month = jul,
abstract = {Neurofibrillary tangles comprised of the microtubule-associated protein
tau are pathological features of Alzheimer's disease and several
other neurodegenerative diseases, such as progressive supranuclear
palsy. We previously overexpressed tau in the substantia nigra of
rats and mimicked some of the neurodegenerative sequelae that occur
in humans such as tangle formation, loss of dopamine neurons, and
microgliosis. To study molecular changes involved in the tau-induced
disease state, we used DNA microarrays at an early stage of the disease
process. A range of adeno-associated virus (AAV9) vector doses for
tau were injected in groups of rats with a survival interval of 2 weeks.
Specific decreases in messages for dopamine-related genes validated
the technique with respect to the dopaminergic cell loss observed.
Of the mRNAs upregulated, there was a dose-dependent effect on multiple
genes involved in immune response such as chemokines, interferon-inducible
genes and leukocyte markers, only in the tau vector groups and not
in dose-matched controls of either transgene-less empty vector or
control green fluorescent protein vector. Histological staining for
dopamine neurons and microglia matched the loss of dopaminergic markers
and upregulation of immune response mRNAs in the microarray data,
respectively. RT-PCR for selected markers confirmed the microarray
results, with similar changes found by either technique. The mRNA
data correlate well with previous findings, and underscore microgliosis
and immune response in the degenerative process following tau overexpression.},
booktitle = {Endocannabinoids signalling in healthy and diseased brain},
issn = {0014-4886},
keywords = {Adeno-associated virus, Neurodegenerative diseases, Microarray, Microtubule-associated
protein tau, Gene transfer, Immune response, Gliosis, Progressive
supranuclear palsy},
url = {http://www.sciencedirect.com/science/article/B6WFG-4YP0N0B-1/2/1fde3a6a0555aff857dae37e6e380fb2}
}
@ARTICLE{Wang2010o,
author = {Wang, Dan Yi and Ray, Arjun and Rodgers, Kathryn and Ergorul, Ceren
and Hyman, Bradley T. and Huang, Wei and Grosskreutz, Cynthia L.},
title = {Global Gene Expression Changes in Rat Retinal Ganglion Cells in Experimental
Glaucoma},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {4084--4095},
number = {8},
month = aug,
abstract = {Purpose.Intraocular pressure (IOP) is an important risk factor in
glaucoma. Gene expression changes were studied in glaucomatous rat
retinal ganglion cells (RGCs) to elucidate altered transcriptional
pathways. Methods.RGCs were back-labeled with Fluorogold. Unilateral
IOP elevation was produced by injection of hypertonic saline into
the episcleral veins. Laser capture microdissection (LCM) was used
to capture an equal number of RGCs from normal and glaucomatous retinal
sections. RNA was extracted and amplified, labeled, and hybridized
to rat genome microarrays, and data analysis was performed. After
selected microarray data were confirmed by RT-qPCR and immunohistochemistry,
biological pathway analyses were performed. Results.Significant changes
were found in the expression of 905 genes, with 330 genes increasing
and 575 genes decreasing in glaucomatous RGCs. Multiple cellular
pathways were involved. Ingenuity pathway analysis demonstrated significant
changes in cardiac {beta}-adrenergic signaling, interferon signaling,
glutamate receptor signaling, cAMP-mediated signaling, chemokine
signaling, 14-3-3-mediated signaling, and G-protein-coupled receptor
signaling. Gene set enrichment analysis showed that the genes involved
in apoptotic pathways were enriched in glaucomatous RGCs. The prosurvival
gene Stat3 was upregulated in response to elevated IOP, and immunohistochemistry
confirmed that Stat3 and phosphorylated-Stat3 levels were increased
in RGCs in experimental glaucoma. In addition, the expression of
several prosurvival genes normally expressed in RGCs was decreased.
Conclusions.There are extensive changes in gene expression in glaucomatous
RGCs involving multiple molecular pathways, including prosurvival
and prodeath genes. The alteration in the balance between prosurvival
and prodeath may contribute to RGC death in glaucoma.},
url = {http://www.iovs.org/cgi/content/abstract/51/8/4084}
}
@ARTICLE{Wang2011ab,
author = {Wang, Dong-Yu and Done, Susan and McCready, David and Boerner, Scott
and Kulkarni, Supriya and Leong, Wey},
title = {A new gene expression signature, the ClinicoMolecular Triad Classification,
may improve prediction and prognostication of breast cancer at the
time of diagnosis},
journal = {Breast Cancer Research},
year = {2011},
volume = {13},
pages = {R92},
number = {5},
abstract = {INTRODUCTION:When making treatment decisions, oncologists often stratify
breast cancer (BC) into a low-risk group (low-grade estrogen receptor-positive
(ER+)), an intermediate-risk group (high-grade ER+) and a high-risk
group that includes Her2+ and triple-negative (TN) tumors (ER-/PR-/Her2-).
None of the currently available gene signatures correlates to this
clinical classification. In this study, we aimed to develop a test
that is practical for oncologists and offers both molecular characterization
of BC and improved prediction of prognosis and treatment response.METHODS:We
investigated the molecular basis of such clinical practice by grouping
Her2+ and TN BC together during clustering analyses of the genome-wide
gene expression profiles of our training cohort, mostly derived from
fine-needle aspiration biopsies (FNABs) of 149 consecutive evaluable
BC. The analyses consistently divided these tumors into a three-cluster
pattern, similarly to clinical risk stratification groups, that was
reproducible in published microarray databases (n = 2,487) annotated
with clinical outcomes. The clinicopathological parameters of each
of these three molecular groups were also similar to clinical classification.RESULTS:The
low-risk group had good outcomes and benefited from endocrine therapy.
Both the intermediate- and high-risk groups had poor outcomes, and
their BC was resistant to endocrine therapy. The latter group demonstrated
the highest rate of complete pathological response to neoadjuvant
chemotherapy; the highest activities in Myc, E2F1, Ras, beta-catenin
and IFN-gamma pathways; and poor prognosis predicted by 14 independent
prognostic signatures. On the basis of multivariate analysis, we
found that this new gene signature, termed the "ClinicoMolecular
Triad Classification" (CMTC), predicted recurrence and treatment
response better than all pathological parameters and other prognostic
signatures.CONCLUSIONS:CMTC correlates well with current clinical
classifications of BC and has the potential to be easily integrated
into routine clinical practice. Using FNABs, CMTC can be determined
at the time of diagnostic needle biopsies for tumors of all sizes.
On the basis of using public databases as the validation cohort in
our analyses, CMTC appeared to enable accurate treatment guidance,
could be made available in preoperative settings and was applicable
to all BC types independently of tumor size and receptor and nodal
status. The unique oncogenic signaling pathway pattern of each CMTC
group may provide guidance in the development of new treatment strategies.
Further validation of CMTC requires prospective, randomized, controlled
trials.},
doi = {10.1186/bcr3017},
issn = {1465-5411},
pubmedid = {21939527},
url = {http://breast-cancer-research.com/content/13/5/R92}
}
@BOOK{Wang2009b,
title = {cDNA and Microarray-Based Technologies},
publisher = {Wiley-VCH Verlag GmbH \& Co. KGaA},
year = {2009},
author = {Wang, Ena and Jin, Ping and Liu, Hui Lui and Stroncek, David F. and
Marincola, Francesco M.},
pages = {79--101},
abstract = {Summary 10.1002/9783527625970.ch5.abs This chapter contains sections
titled:},
booktitle = {Tumor-Associated Antigens},
issn = {9783527625970},
keywords = {microarray technology, tumor-associated antigen (TAA), gene expression,
gene profiling, high throughput analysis, RNA amplification},
url = {http://dx.doi.org/10.1002/9783527625970.ch5}
}
@ARTICLE{Wang2004,
author = {Wang, Ena and Lichtenfels, Rudolf and Bukur, Jurgen and Ngalame,
Yvonne and Panelli, Monica C. and Seliger, Barbara and Marincola,
Francesco M.},
title = {Ontogeny and Oncogenesis Balance the Transcriptional Profile of Renal
Cell Cancer},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {7279--7287},
number = {20},
month = oct,
abstract = {Global transcript analysis is increasingly used to describe cancer
taxonomies beyond the microscopic reach of the eye. Diagnostic and
prognostic portraits are formulated by ranking cancers according
to transcriptional proximity. However, the role that distinct biological
factors play in defining these portraits remains undefined. It is
likely that the transcriptional repertoire of cancers depends, on
one hand, on the anamnestic retention of their ontogenesis and, on
the other, on the emergence of novel expression patterns related
to oncogenesis. We compared the transcriptional profile of primary
renal cell cancers (RCCs) with that of normal kidney tissue and several
epithelial cancers of nonrenal origin to weigh the contribution that
ontogeny and oncogenesis make in molding their genetic profile. Unsupervised
global transcript analysis demonstrated that RCCs retain transcriptional
signatures related to their ontogeny and cluster close to normal
renal epithelium. When renal lineage-associated genes are removed
from the analysis and cancer-specific genes are analyzed, RCCs segregate
with other cancers with limited lineage specificity underlying a
predominance of the oncogenic process over lineage specificity. However,
a RCC-specific set of oncogenesis-related genes was identified and
surprisingly shared by sarcomas. In summary, the transcriptional
portrait of primary RCCs is largely dominated by ontogeny. Genes
responsible for lineage specificity may represent poor molecular
targets for immune or drug therapy. Most genes associated with oncogenesis
are shared with other cancers and may represent better therapeutic
targets. Finally, a small subset of genes is associated with lineage-specific
oncogenesis, and these may provide information regarding the biological
behavior of RCCs and facilitate diagnostic classification of RCCs.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/20/7279}
}
@ARTICLE{Wang2005a,
author = {Wang, Ena and Ngalame, Yvonne and Panelli, Monica C. and Nguyen-Jackson,
Hoainam and Deavers, Michael and Mueller, Peter and Hu, Wei and Savary,
Cherylyn A. and Kobayashi, Ryuji and Freedman, Ralph S. and Marincola,
Francesco M.},
title = {Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread
of Ovarian Cancer},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {113--122},
number = {1},
month = jan,
abstract = {Purpose: Epithelial ovarian cancer (EOC) is characterized by early
peritoneal involvement ultimately contributing to morbidity and mortality.
To study the role of the peritoneum in fostering tumor invasion,
we analyzed differences between the transcriptional repertoires of
peritoneal tissue lacking detectable cancer in patients with EOC
versus benign gynecologic disease. Experimental Design: Specimens
were collected at laparotomy from patients with benign disease (b)
or malignant (m) ovarian pathology and comprised primary ovarian
tumors, paired bilateral specimens from adjacent peritoneum and attached
stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and
peripheral blood mononuclear cells. Specimens were immediately frozen.
RNA was amplified by in vitro transcription and cohybridized with
reference RNA to a custom-made 17.5k cDNA microarray. Results: Principal
component analysis and unsupervised clustering did not segregate
specimens from patients with benign or malignant pathology. Class
comparison identified differences between benign and malignant PE
and ST specimens deemed significant by permutation test (P = 0.027
and 0.012, respectively). A two-tailed Student's t test identified
402 (bPE versus mPE) and 663 (mST versus bST) genes differentially
expressed at a significance level of P2 [≤] 0.005 when all available
paired samples from each patient were analyzed. The same comparison
using one sample per patient reduced the pool of differentially expressed
genes but retained permutation test significance for bST versus mST
(P = 0.031) and borderline significance for bPE versus mPE (P = 0.056)
differences. Conclusions: The presence of EOC may foster peritoneal
implantation and growth of cancer cells by inducing factors that
may represent molecular targets for disease control.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/1/113}
}
@ARTICLE{Wang2008,
author = {Wang, Er-Jia and Snyder, Ronald D. and Fielden, Mark R. and Smith,
Roger J. and Gu, Yi-Zhong},
title = {Validation of putative genomic biomarkers of nephrotoxicity in rats},
journal = {Toxicology},
year = {2008},
volume = {246},
pages = {91--100},
number = {2-3},
month = apr,
abstract = {Drug-induced renal injury is a common finding in the early preclinical
phase of drug development. But the specific genes responding to renal
injury remain poorly defined. Identification of drug-induced gene
changes is critical to provide insights into molecular mechanisms
and detection of renal damage. To identify genes associated with
the development of drug-induced nephrotoxicity, a literature survey
was conducted and a panel of 48 genes was selected based on gene
expression changes in multiple published studies. Male Sprague-Dawley
rats were dosed daily for 1, 3 or 5 days to the known nephrotoxicants
gentamicin, bacitracin, vancomycin and cisplatin, or the known hepatotoxicants
ketoconazole, 1-naphthyl isothiocyanate and 4,4-diaminodiphenylmethane.
Histopathological evaluation and clinical chemistry revealed renal
proximal tubular necrosis in rats treated with the nephrotoxicants,
but not from those treated with the hepatotoxicants. RNA was extracted
from the kidney, and RT-PCR was performed to evaluate expression
profiles of the selected genes. Among the genes examined, 24 genes
are confirmed to be highly induced or repressed in rats treated with
nephrotoxicants; further investigation identified that 5 of the 24
genes were also altered by hepatotoxicants. These data led to the
identification of a set of genomic biomarker candidates whose expression
in kidney is selectively regulated only by nephrotoxicants. Among
those genes displaying the highest expression changes specifically
in nephrotoxicant-treated rats were kidney injury molecule 1 (Kim1),
lipocalin 2 (Lcn2), and osteopontin (Spp1). The establishment of
such a genomic marker set offers a new tool in our ongoing quest
to monitor nephrotoxicity.},
issn = {0300-483X},
keywords = {Rat, Gene expression, Toxicogenomics, Nephrotoxicity, Biomarkers},
url = {http://www.sciencedirect.com/science/article/B6TCN-4RKTNFV-1/2/2d614b41f3ccc8722ded0d4b83fb6eb3}
}
@ARTICLE{Wang2009c,
author = {Wang, Fangjing and Kuang, Yu and Salem, Nicolas and Anderson, Paul
W and Lee, Zhenghong},
title = {Cross-species hybridization of woodchuck hepatitis viral infection-induced
woodchuck hepatocellular carcinoma using human, rat and mouse oligonucleotide
microarrays},
journal = {Journal of Gastroenterology and Hepatology},
year = {2009},
volume = {24},
pages = {605--617},
number = {4},
abstract = {Abstract Background and Aim:  We aimed to evaluate the transcriptional
characteristics of viral infection-induced woodchuck hepatocellular
carcinoma (HCC), to compare the use of human, rat and mouse gene
arrays for cross-species hybridization, and to look into gene expression
profiles in woodchuck HCC by the combined use of these arrays. Methods: 
Commercially available human, rat and mouse oligonucleotide microarrays
were used to determine the gene expression profiles on the same woodchuck
liver samples. Differentially expressed genes between HCC and the
surrounding hepatic tissues found in the arrays were selected for
quantitative reverse transcription polymerase chain reaction. Results: 
Despite the difference in the number of the probes from each array,
the percentage of genes that were detectable was similar. Stringent
microarray data analysis using both supervised and unsupervised methods
identified 281 differentially expressed genes via the human array
with a false discovery rate (FDR) of 0.99%, 107 genes via the rat
array with an FDR of 1.85% and 78 genes via the mouse array with
an FDR of 7.41%. Eleven genes were differentially changed in all
three arrays that include the upregulation of NPM1, H2AFZ, EEF1G,
HNRPAB, RPS18, EIF5, CKS2, ARIH1, RPS12 and RPS10, and the downregulation
of EGR1. The quantitative reverse transcription polymerase chain
reaction with woodchuck-specific primers confirmed the reliability
of the microarray results. Conclusion:  This study further demonstrated
the utility of cross-species hybridization of microarrays on woodchuck
HCC. A combined use of three types of arrays identified more differential
genes in HCC than individual arrays with the human array providing
the richest information among the three arrays used.},
issn = {1440-1746},
keywords = {cross-species hybridization, hepatitis B virus, hepatocellular carcinoma
(HCC), human, microarray, mouse, rat, woodchuck},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1440-1746.2008.05581.x}
}
@ARTICLE{Wang2010t,
author = {Wang, Fengjun and Zheng, Zhiguo and Guo, Jiangfeng and Ding, Xianfeng},
title = {Correlation and quantitation of microRNA aberrant expression in tissues
and sera from patients with breast tumor},
journal = {Gynecologic Oncology},
year = {2010},
volume = {119},
pages = {586--593},
number = {3},
month = dec,
abstract = {Objectives MicroRNAs (miRNAs) have been underlined as a promising
potential biomarker for breast cancer but are limited to tissue specimens.
Clinical specimens of sera are more abundant and more conveniently
collected than tissues. This work was designed to investigate the
expression and correlation of a selected panel of miRNAs associated
with breast tumor in tissues and matching serum samples.Methods Tumor
tissues, adjacent non-tumor tissues and matching serum samples were
collected from 68 patients with newly diagnosed breast tumors. Normal
control sera were collected from 40 healthy subjects. A panel of
6 miRNAs (miRNA-21, 106a, 126, 155, 199a and 335) were selected and
their aberrant expression levels were quantified by using real-time
PCR technique.Results A high correlation of miRNA expression level
was found between breast tumor tissues and sera. MiR-21, miR-106a
and miR-155 were significantly over-expressed in the tumor specimens
compared with those in normal controls (P < 0.05), whereas miR-126,
miR-199a and miR-335 were significantly under-expressed (P < 0.05).
Furthermore, the relative expression of miR-21, miR-126, miR-155,
miR-199a and miR-335 was closely associated with clinicopathologic
features of breast cancer (P < 0.05), such as histological tumor
grades and sex hormone receptor expression.Conclusions Selective
expression and modulation of miRNAs could be potential blood-based
biomarkers for breast cancer diagnosis, grading and prognosis. Our
results should encourage further studies on the use of miRNAs in
serum samples as an easy and convenient method of breast cancer screening.},
issn = {0090-8258},
keywords = {MicroRNA, Breast cancer, Serum, Biomarker},
url = {http://www.sciencedirect.com/science/article/B6WG6-50WYSHV-1/2/6c55365e014b47829e8de20df8b739e1}
}
@ARTICLE{Wang2004a,
author = {Wang, Gan and Chuang, Lynn and Zhang, Xiaohong and Colton, Stephanie
and Dombkowski, Alan and Reiners, John and Diakiw, Amy and Xu, Xiaoxin
Susan},
title = {The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated
cell cycle regulation},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {2231--2240},
number = {7},
month = apr,
abstract = {XPC is an important DNA damage recognition protein involved in DNA
nucleotide excision repair. We have studied the role of the XPC protein
in cisplatin treatment-mediated cell cycle regulation. Through the
comparison of microarray data obtained from human normal fibroblasts
and two individual XPC-defective cell lines, 486 genes were identified
as XPC-responsive genes in the cisplatin treatment (with a minimal
1.5-fold change) and 297 of these genes were further mapped to biological
pathways and gene ontologies. The cell cycle and cell proliferation-related
genes were the most affected genes by the XPC defect in the cisplatin
treatment. Many other cellular function genes were also affected
by the XPC defect in the treatment. Western blot hybridization results
revealed that the XPC defect reduced the p53 responses to the cisplatin
treatment. The ability to activate caspase-3 was also attenuated
in the XPC cells with the treatment. These results suggest that the
XPC protein plays a critical role in initiating the cisplatin DNA
damaging treatment-mediated signal transduction process, resulting
in activation of the p53 pathway and cell cycle arrest that allow
DNA repair and apoptosis to take place. These results reveal an important
role of the XPC protein in the cancer prevention.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/7/2231}
}
@ARTICLE{Wang2011j,
author = {Wang, Guifeng and Wang, Gang and Zhang, Xiaowei and Wang, Fang and
Song, Rentao},
title = {Isolation of High Quality RNA from Cereal Seeds Containing High Levels
of Starch},
journal = {Phytochemical Analysis},
year = {2011},
pages = {n/a--n/a},
abstract = {IntroductionCereals are an important source of food, feed and fuel
with a rapidly increasing global demand. However, cereal seeds contain
high levels of starch and polysaccharides, making the isolation of
high quality RNA extremely difficult.ObjectiveTo develop a novel
method for extracting high quality total RNA from various starch-
and polysaccharides-rich cereal seeds, such as maize, rice, sorghum
and wheat.MethodologyWe developed a modified sodium dodecyl sulphate
(SDS)/TRIzol method. The combined use of a Tris buffer (pH 9.0) and
SDS before TRIzol extraction effectively resolved the problem of
seed homogenate solidification in such a buffer. A high concentration
of SDS was used separately, not only to promote cell lysis but also
to effectively dissolve seed sample containing high levels of starch.
Moreover, acid phenol saturated with 0.1 m citrate buffer (pH 4.3)
was used to separate RNA from DNAs, proteins and high levels of starch.
This rapid protocol was compared with other RNA isolation methods
preferentially used for plants rich in polysaccharides and secondary
metabolites.ResultsGel electrophoresis analysis indicated that the
extracted total RNA had good integrity without apparent DNA contamination.
Furthermore, an A260/280 ratio of approximately 2.0, an A260/230
ratio of more than 2.0 and RIN values of more than 8.6 indicated
that the isolated RNA was of high purity. The isolated RNA was suitable
for subsequent molecular manipulations, such as reverse-transcription
polymerase chain reaction (PCR), rapid amplification of cDNA ends
(RACE) and real-time PCR.ConclusionThe study has described an easy,
efficient and highly reproducible method for RNA isolation from various
cereal seeds.},
doi = {10.1002/pca.1337},
issn = {1099-1565},
keywords = {RNA isolation, maize, rice, seed, sorghum, starch, wheat},
publisher = {John Wiley \& Sons, Ltd},
url = {http://dx.doi.org/10.1002/pca.1337}
}
@ARTICLE{Wang2010f,
author = {Wang, Guoqing and Wang, Rui and Ferris, Barbara and Salit, Jacqueline
and Yael Strulovici-Barel, Yael and Hackett, Neil and Crystal, Ronald},
title = {Smoking-mediated up-regulation of GAD67 expression in the human airway
epithelium },
journal = {Respiratory Research},
year = {2010},
volume = {11},
pages = {150},
number = {1},
abstract = {BACKGROUND:The production of gamma-amino butyric acid (GABA) is dependent
on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze
the decarboxylation of glutamate to GABA. Based on studies suggesting
a role of the airway epithelial GABAergic system in asthma-related
mucus overproduction, we hypothesized that cigarette smoking, another
disorder associated with increased mucus production, may modulate
GABAergic system-related gene expression levels in the airway epithelium.
METHODS:We assessed expression of the GABAergic system in human airway
epithelium obtained using bronchoscopy to sample the epithelium and
microarrays to evaluate gene expression. RT-PCR was used to confirm
gene expression of GABAergic system gene in large and small airway
epithelium from heathy nonsmokers and healthy smokers. The differences
in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry
and Western analysis.RESULTS:The data demonstrate there is a complete
GABAergic system expressed in the large and small human airway epithelium,
including glutamate decarboxylase, GABA receptors, transporters and
catabolism enzymes. Interestingly, of the entire GABAergic system,
smoking modified only the expression of GAD67, with marked up-regulation
of GAD67 gene expression in both large (4.1-fold increase, p<0.01)
and small airway epithelium of healthy smokers (6.3-fold increase,
p<0.01). At the protein level, Western analysis confirmed the increased
expression of GAD67 in airway epithelium of healthy smokers compared
to healthy nonsmokers (p<0.05). There was a significant positive
correlation between GAD67 and MUC5AC gene expression in both large
and small airway epithelium (p<0.01), implying a link between GAD67
and mucin overproduction in association with smoking. CONCLUSIONS:In
the context that GAD67 is the rate limiting enzyme in GABA synthesis,
the correlation of GAD67 gene expression with MUC5AC expressions
suggests that the up-regulation of airway epithelium expression of
GAD67 may contribute to the increase in mucus production observed
in association with cigarette smoking. Trial registration: NCT00224198;
NCT00224185},
doi = {10.1186/1465-9921-11-150},
issn = {1465-9921},
pubmedid = {21034448},
url = {http://respiratory-research.com/content/11/1/150}
}
@ARTICLE{Wang2010k,
author = {Wang, Guo-Peng and Chatterjee, Ishani and Batts, Shelley A. and Wong,
Hiu Tung and Gong, Tzy-Wen and Gong, Shu-Sheng and Raphael, Yehoash},
title = {Notch signaling and Atoh1 expression during hair cell regeneration
in the mouse utricle},
journal = {Hearing Research},
year = {2010},
volume = {267},
pages = {61--70},
number = {1-2},
month = aug,
abstract = {The mammalian vestibular epithelium has a limited capacity for spontaneous
hair cell regeneration. The mechanism underlying the regeneration
is not well understood. Because the Notch signaling pathway mediates
the formation of the sensory epithelial mosaic patterning during
ear development, it may also play a role in hair cell regeneration
in the mature mammalian vestibular epithelium after a lesion. To
investigate the process of spontaneous regeneration in the vestibular
epithelium vis-à-vis changes in Notch signaling, we induced a unilateral
lesion by infusing streptomycin into the mouse posterior semicircular
canal, and examined Notch signaling molecules and their mRNA expression
levels by immunohistochemistry and quantitative real-time polymerase
chain reaction (qRTPCR), respectively. We detected Jagged1 in supporting
cells in both normal and lesioned utricles. Atoh1, a marker for early
developing hair cells, was absent in the intact mature tissue, but
re-appeared after the lesion. Many cells were either positive for
both Atoh1 and myosin VIIa, or for one of them. qRTPCR data showed
a post trauma decrease of Hes5 and an increase in Atoh1. Atoh1 up-regulation
may either be a result of Hes5 down-regulation or mediated by another
signaling pathway.},
issn = {0378-5955},
url = {http://www.sciencedirect.com/science/article/B6T73-4YYGGYX-1/2/f61441d77d708bf0dd4137ec50b867b1}
}
@ARTICLE{Wang2011aa,
author = {Wang, H. and Chavali, S. and Mobini, R. and Muraro, A. and Barbon,
F. and Boldrin, D. and Ã…berg, N. and Benson, M.},
title = {A pathway-based approach to find novel markers of local glucocorticoid
treatment in intermittent allergic rhinitis},
journal = {Allergy},
year = {2011},
volume = {66},
pages = {132--140},
number = {1},
abstract = {To cite this article: Wang H, Chavali S, Mobini R, Muraro A, Barbon
F, Boldrin D, Ã…berg N, Benson M. A pathway-based approach to find
novel markers of local glucocorticoid treatment in intermittent allergic
rhinitis. Allergy 2011; 66: 132–140.AbstractBackground:  Glucocorticoids
(GCs) may affect the expression of hundreds of genes in different
cells and tissues from patients with intermittent allergic rhinitis
(IAR). It is a formidable challenge to understand these complex changes
by studying individual genes. In this study, we aimed to identify
(i) pathways affected by local GC treatment and (ii) examine if those
pathways could be used to find novel markers of local GC treatment
in nasal fluids from patients with IAR.Methods:  Gene expression
microarray- and iTRAQ-based proteomic analyses of nasal fluids, nasal
fluid cells and nasal mucosa from patients with IAR were performed
to find pathways enriched for differentially expressed genes and
proteins. Proteins representing those pathways were analyzed with
ELISA in an independent material of nasal fluids from 23 patients
with IAR before and after treatment with a local GC.Results:  Transcriptomal
and proteomic high-throughput analyses of nasal fluids, nasal fluid
cells and nasal mucosal showed that local GC treatment affected a
wide variety of pathways in IAR such as the glucocorticoid receptor
pathway and the acute phase response pathway. Extracellular proteins
encoded by genes in those pathways were analyzed in an independent
material of nasal fluids from patients. Proteins that changed significantly
in expression included known biomarkers such as eosinophil cationic
protein but also proteins that had not been previously described
in IAR, namely CCL2, M-CSF, CXCL6 and apoH.Conclusion:  Pathway-based
analyses of genomic and proteomic high-throughput data can be used
as a complementary approach to identify novel potential markers of
GC treatment in IAR.},
doi = {10.1111/j.1398-9995.2010.02444.x},
issn = {1398-9995},
keywords = {allergic rhinitis, gene expression microarray analysis, glucocorticoids,
proteomics},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1398-9995.2010.02444.x}
}
@ARTICLE{Wang2007,
author = {Wang, Hong and Edens, Neile K.},
title = {mRNA expression and antilipolytic role of phosphodiesterase 4 in
rat adipocytes in vitro},
journal = {J. Lipid Res.},
year = {2007},
volume = {48},
pages = {1099--1107},
number = {5},
month = may,
abstract = {Adipocyte lipolysis is dependent on an increase in the intracellular
concentration of cAMP. Intracellular phosphodiesterases (PDEs) hydrolyze
cAMP and limit stimulation of lipolysis. In the present study, the
mRNA expression of PDE4 subtypes and the antilipolytic role of PDE4
in rat adipocytes were investigated. Fragments encoding PDE4A (233
bp), PDE4B (786 bp), PDE4C (539 bp), and PDE4D (262 bp) sequences
were amplified by RT-PCR. The mRNA expression of PDE4 subtypes (A,
B, C, D) determined by real-time quantitative PCR was 7, 18.7, 18.9,
and 7.2% relative to PDE3B. Inhibition of PDE4 by rolipram increased
basal lipolysis and reversed in part prostaglandin E2 antilipolysis.
The combination of PDE3 and PDE4 inhibitors synergistically reversed
both prostaglandin E2 and phenylisopropyl adenosine antilipolysis.
Stimulation of adipocytes with prostaglandin E2 increased total PDE
activity and PDE3 activity measured by hydrolysis of 3[H]cAMP by
the particulate fraction of adipocytes. The present study confirmed
that mRNAs for all four PDE4 subtypes were expressed in rat adipocytes,
with PDE4B and PDE4C predominant. Moreover, PDE4 not only limits
the rate of basal lipolysis but also contributes to prostaglandin
E2 antilipolysis in rat adipocytes.},
url = {http://www.jlr.org/cgi/content/abstract/48/5/1099}
}
@ARTICLE{Wang2010r,
author = {Wang, Huafeng and Gao, Yabo and Jin, Xiaolong and Xiao, Jiacheng},
title = {Expression of contactin associated protein-like 2 in a subset of
hepatic progenitor cell compartment identified by gene expression
profiling in hepatitis B virus-positive cirrhosis},
journal = {Liver International},
year = {2010},
volume = {30},
pages = {126--138},
number = {1},
abstract = {Abstract Background: Hepatic progenitor cells (HPC), a cell compartment
capable of differentiating into hepatocytic and biliary lineages,
may give rise to the formation of intermediate hepatobiliary cells
(IHBC) or ductular reactions (DR). Aims: The aim of this study was
to analyse the gene expression profiles of DR in cirrhosis and further
investigate novel proteins expressed by HPC and their intermediate
progeny. Methods: DR in hepatitis B virus (HBV)-positive cirrhotic
liver tissues adjacent to hepatocellular carcinoma and interlobular
bile ducts (ILBDs) in normal liver tissues were isolated by laser
capture microdissection and then subjected to microarray analysis.
Differential gene expression patterns were verified by quantitative
reverse transcriptase-polymerase chain reaction and immunohistochemistry
on serial sections. HPC and their intermediate progeny were recognized
by immunostaining with hepatocytic and biliary markers [HepPar1,
cytokeratin (CK)7, CK19, neural cell adhesion molecule (NCAM), epithelial
cell adhesion molecule (EpCAM)]. Results: A total of 88 genes showed
upregulation in DR compared with ILBDs. Gene ontology analyses revealed
that these upregulated genes were mostly associated with cell adhesion,
immune response and the metabolic process. Contactin associated protein-like
2 (CNTNAP2) was first confirmed to be a novel protein expressed in
a subpopulation of DR that was positive for CK7, NCAM or EpCAM. In
addition, immunoreactivity for CNTNAP2 was also noted in a subset
of isolated CK7-positive HPC as well as some ductular IHBC positive
for CK19 and HepPar1 in DR. Conclusion: CNTNAP2 is specifically associated
with the emergence of ductular populations and may be identified
as a novel protein for defining a subset of HPC and their intermediate
progeny in cirrhosis.},
issn = {1478-3231},
keywords = {CNTNAP2, ductular reactions, gene expression profiling, hepatic progenitor
cells, laser capture microdissection},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1478-3231.2009.02151.x}
}
@ARTICLE{Wang2008a,
author = {Wang, Hui and He, Lizhong and Lensch, Martin and Gabius, Hans-Joachim
and Fee, Conan J. and Middelberg, Anton P. J.},
title = {Single-Site Cys-Substituting Mutation of Human Lectin Galectin-2:
Modulating Solubility in Recombinant Production, Reducing Long-Term
Aggregation, and Enabling Site-Specific MonoPEGylation},
journal = {Biomacromolecules},
year = {2008},
volume = {9},
pages = {3223-3230},
number = {11},
note = {PMID: 18942878},
doi = {10.1021/bm800801b},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/bm800801b},
url = {http://pubs.acs.org/doi/abs/10.1021/bm800801b}
}
@ARTICLE{Wang2005b,
author = {Wang, Hali and Li, Xinmin and Tomin, Emre and Doty, Stephen B. and
Lane, Joseph M. and Carney, Darrell H. and Ryaby, James T.},
title = {Thrombin peptide (TP508) promotes fracture repair by up-regulating
inflammatory mediators, early growth factors, and increasing angiogenesis},
journal = {J. Orthop. Res.},
year = {2005},
volume = {23},
pages = {671--679},
number = {3},
abstract = {Abstract 10.1016/j.orthres.2004.10.002.abs Previous studies have shown
that a single injection of thrombin peptide (TP508) accelerates fracture
repair in a closed rat femoral fracture model. The present study
was conducted to elucidate the molecular mechanisms of TP508 action
using Affymetrix genomescale profiling and to link early gene expression
changes to fracture histology and bone strength changes. Treatment
of femoral fractures with TP508 accelerated fracture repair as determined
by destructive torsion testing. Blinded histological analysis demonstrated
that TP508-treated fracture callus had a significant increase in
blood vessels relative to the controls. Gene array analysis showed
that TP508 significantly induced expression of early growth factors,
inflammatory response modifiers, and angiogenesis-related genes.
This study therefore suggests that TP508 promotes fracture repair
through a mechanism that involves an increased induction of a number
of growth factors, enhanced expression of inflammatory mediators,
and angiogenesis-related genes. © 2004 Orthopaedic Research Society.
Published by Elsevier Ltd. All rights reserved.},
issn = {1554-527X},
keywords = {Fracture repair, TP508, Gene expression, Early growth factors, Angiogenesis,
Microarray analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1016/j.orthres.2004.10.002}
}
@ARTICLE{Wang2010u,
author = {Wang, Haifang and Liu, Yuting and Briesemann, Marko and Yan, Jun},
title = {Computational analysis of gene regulation in animal sleep deprivation},
journal = {Physiol Genomics},
year = {2010},
volume = {42},
pages = {427--436},
number = {3},
month = aug,
abstract = {Sleep is an animal behavior shared by a wide range of species, suggesting
that it must serve fundamental functions. However, the functions
and molecular mechanisms underlying sleep are largely unknown. Through
a meta-analysis of all available short-term sleep deprivation (SD)
microarray data in mouse brain, we identified 91 key mouse SD-affected
genes and two RBM3 isoforms showing opposite changes of expression
during SD. Although most of the key SD-affected genes showed consistent
changes of expression during SD across brain subregions despite their
heterogeneous basal expression levels, we also identified the genes
whose SD responses strongly depend upon the brain subregion. A gene
regulatory network was also constructed for these genes showing that
cAMP-responsive element (CRE) is one of the key cis-regulatory elements
controlling SD-affected genes. We observed that SD during an animal's
normal sleeping time could significantly disturb the circadian oscillation
of clock genes. Surprisingly, synaptogenesis markers were significantly
underexpressed in SD mice, differing from the previous findings in
rat and fly. Comparing SD microarray data in mouse, rat, sparrow,
and fly, we identified Egr and Nr4a gene families as conserved SD-affected
genes, thus shedding new light on the origin of sleep in animals.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42/3/427}
}
@ARTICLE{Wang2011r,
author = {Hehai Wang and Liming Luan and Tianbing Ding and Naoko Brown and
Jeff Reese and B.C. Paria},
title = {Dynamics of zonula occludens-2 expression during preimplantation
embryonic development in the hamster},
journal = {Theriogenology},
year = {2011},
volume = {76},
pages = {678 - 686},
number = {4},
abstract = {The objective was to study the expression of zonula occludens-2, a
tight junction protein, during preimplantation hamster embryonic
development, to predict its possible localization, source, and roles
in trophectoderm differentiation and blastocyst formation in this
species. Comparison of zonula occludens-2 expression pattern between
the hamster and mouse preimplantation embryos from the zygote up
to the blastocyst stage was also an objective of this study. Zonula
occludens-2 localization was noted in nuclei of blastomeres in all
stages of hamster and mouse embryonic development. Compared to mice,
where zonula occludens-2 was first localized in the interblastomere
membrane at the morula stage, hamster embryos had membranous zonula
occludens-2 localization from the 2-cell stage onwards. Based on
combined results of immunolocalization study in parthenogenic embryos
and ovarian and epididymal sections, and quantitative PCR done in
oocytes and all developmental stages of preimplantation embryos,
perhaps there was a carry-over of zonula occludens-2 proteins or
mRNA from the dam to the embryo. Based on these findings, we inferred
that maternally derived zonula occludens-2 was involved in nuclear
functions, as well as differentiation of blastomeres and blastocoel
formation during preimplantation embryonic development in the hamster.},
doi = {10.1016/j.theriogenology.2011.03.021},
issn = {0093-691X},
keywords = {Zonula occludens-2},
url = {http://www.sciencedirect.com/science/article/pii/S0093691X11001580}
}
@ARTICLE{Wang2009d,
author = {Wang, Heng and Nattanmai, Seela and Kramer, Laura D. and Bernard,
Kristen A. and Tavakoli, Norma P.},
title = {A duplex real-time reverse transcriptase polymerase chain reaction
assay for the detection of California serogroup and Cache Valley
viruses},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2009},
volume = {65},
pages = {150--157},
number = {2},
month = oct,
abstract = {A duplex TaqMan real-time reverse transcriptase polymerase chain reaction
(PCR) assay was developed for the detection of California (CAL) serogroup
viruses and Cache Valley virus (CVV), for use in human surveillance.
The targets selected for the assay were the sequences encoding the
nucleocapsid protein of CAL and the G1 glycoprotein of CVV. Conserved
regions were selected by aligning genetic sequences from various
strains available in the GenBank database. Primers and probes were
selected in conserved regions. The assay sensitivity was 75 gene
copies (gc)/reaction for CAL serogroup viruses and 30 gc/reaction
for CVV. The performance of the assay was linear over at least 6
log10 gc. The assay was specific, given that it did not cross-react
with a variety of pathogens. It did, however, detect 11 viruses within
the CAL serogroup and 12 CVV isolates. The use of an internal control
ensured that possible inefficiency in nucleic acid extraction or
PCR inhibition would be detected.},
issn = {0732-8893},
keywords = {Molecular detection, Real-time RT-PCR, California serogroup viruses,
Cache Valley virus},
url = {http://www.sciencedirect.com/science/article/B6T60-4X6PHFB-B/2/a010ff74155e6a5ec804a25b3422f638}
}
@ARTICLE{Wang2009e,
author = {Wang, Hongfeng and Rodriguez-Osorio, Nelida and Feugang, Jean Magloire
and Jung, Song-Yi and Garrison, Kriston and Wolgemuth, Christi and
Greer, Laura and Crenshaw, Mark and Memili, Erdogan},
title = {Effects of culture media and inhibitors on biology of porcine early
embryonic development in vitro},
journal = {Livestock Science},
year = {2009},
volume = {121},
pages = {102--107},
number = {1},
month = mar,
abstract = {In vitro-production of porcine embryos is crucial for biomedical and
agricultural research, however, current culture systems for porcine
embryos are sub-optimal, and the developmental potential of in vitro-produced
embryos is not well studied. The objectives of this study were to
evaluate whether PZM-3 or NCSU-23 better support porcine embryo development
and the effects of [alpha]-amanitin and cycloheximide on porcine
embryonic development. Briefly, porcine presumptive zygotes were
produced after in vitro maturation/fertilization (IVM/IVF) and cultured
either in NCSU-23 or PZM-3 culture media. Transcript levels of BAX
and BCL2L1 genes from blastocysts were detected by using Real-time
PCR. The effects of [alpha]-amanitin and cycloheximide were evaluated
for the role of inhibiting transcription and translation during early
porcine embryogenesis. Results showed that both cleavage and blastocyst
rates decreased significantly in NCSU-23 group compared as PZM-3
group. However, BAX and BCL2L1 transcript levels were similar in
blastocysts cultured in both PZM-3 and NCSU-23 media. When porcine
embryos cultured in PZM-3, cleavage rates were significantly decreased
in the present of cycloheximide and both [alpha]-amanitin and cycloheximide
treatments completely inhibited the blastocyst formation. Results
showed that PZM-3 medium better supported porcine early embryonic
development than NCSU-23 medium, and the inhibition of embryonic
genome activation does not completely stop embryo cleavage but prevents
development to the blastocyst stage.},
issn = {1871-1413},
keywords = {Porcine, Embryo, PZM-3, [alpha]-Amanitin, Cycloheximide},
url = {http://www.sciencedirect.com/science/article/B7XNX-4TB9PBF-1/2/b7ef73032552e37cdbd7ca7e8dad0f0f}
}
@ARTICLE{Wang2002,
author = {Wang, H. and Sun, H. and Della Penna, K. and Benz, R. J. and Xu,
J. and Gerhold, D. L. and Holder, D. J. and Koblan, K. S.},
title = {Chronic neuropathic pain is accompanied by global changes in gene
expression and shares pathobiology with neurodegenerative diseases},
journal = {Neuroscience},
year = {2002},
volume = {114},
pages = {529--546},
number = {3},
month = oct,
abstract = {Neuropathic pain is induced by injury or disease of the nervous system.
Studies aimed at understanding the molecular pathophysiology of neuropathic
pain have so far focused on a few known molecules and signaling pathways
in neurons. However, the pathophysiology of neuropathic pain appears
to be very complex and remains poorly understood. A global understanding
of the molecular mechanisms involved in neuropathic pain is needed
for a better understanding of the pathophysiology and treatment of
neuropathic pain. Towards this end, we examined global gene expression
changes as well as the pathobiology at the cellular level in a spinal
nerve ligation neuropathic pain model using DNA microarray, quantitative
real-time PCR and immunohistochemistry. We found that the behavioral
hypersensitivity that is manifested in the persistent pain state
is accompanied by previously undescribed changes in gene expression.
In the DRG, we found regulation of: (1) immediate early genes; (2)
genes such as ion channels and signaling molecules that contribute
to the excitability of neurons; and (3) genes that are indicative
of secondary events such as neuroinflammation. In addition, we studied
gene regulation in both injured and uninjured DRG by quantitative
PCR, and observed differential gene regulation in these two populations
of DRGs. Furthermore, we demonstrated unexpected co-regulation of
many genes, especially the activation of neuroinflammation markers
in both the PNS and CNS. The results of our study provide a new picture
of the molecular mechanisms that underlie the complexity of neuropathic
pain and suggest that chronic pain shares common pathobiology with
progressive neurodegenerative disease.},
issn = {0306-4522},
keywords = {persistent pain, gene regulation, dorsal root ganglion, spinal cord,
DNA microarray, neuroinflammation},
url = {http://www.sciencedirect.com/science/article/B6T0F-46P9MSK-3/2/ad0393314a74c9ad1c00515e81e1e740}
}
@ARTICLE{Wang2007a,
author = {Wang, Han and Zhou, Qingchun and Kesinger, Jason W. and Norris, Chad
and Valdez, Cammi},
title = {Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish},
journal = {Exp Biol Med},
year = {2007},
volume = {232},
pages = {1170--1180},
number = {9},
month = oct,
abstract = {We previously determined that yquem harbors a mutation in the gene
encoding uroporphyrinogen decarboxylase (UROD), the fifth enzyme
in heme biosynthesis, and established zebrafish yquem (yqetp61) as
a vertebrate model for human hepatoery-thropoietic porphyria (HEP).
Here we report that six exocrine peptidase precursor genes, carboxypeptidase
A, trypsin precursor, trypsin like, chymotrypsinogen B1, chymotrypsinogen
1-like, and elastase 2 like, are downregulated in yquem/urod (-/-),
identified initially by microarray analysis of yquem/urod zebrafish
and, subsequently, confirmed by in situ hybridization. We then determined
downregulation of these six zymogens specifically in the exocrine
pancreas of sauternes (sautb223) larvae, carrying a mutation in the
gene encoding {delta}-amino-levulinate synthase (ALAS2), the first
enzyme in heme biosynthesis. We also found that ptf1a, a transcription
factor regulating exocrine zymogens, is downregulated in both yquem/urod
(-/-) and sau/alas2 (-/-) larvae. Further, hemin treatment rescues
expression of ptf1a and these six zymogens in both yquem/urod (-/-)
and sauternes/alas2 (-/-) larvae. Thus, it appears that heme deficiency
downregulates ptf1a, which, in turn, leads to downregulation of exocrine
zymogens. Our findings provide a better understanding of heme deficiency
pathogenesis and enhance our ability to diagnose and treat patients
with porphyria or pancreatic diseases.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/232/9/1170}
}
@ARTICLE{Wang2009f,
author = {Wang, Huan-You and Ding, Jiantao and Vasef, Mohammad A. and Wilson,
Kathleen S.},
title = {A bcr3/Short Form PML-RAR{alpha} Transcript in an Acute Promyelocytic
Leukemia Resulted From a Derivative Chromosome 17 Due to Submicroscopic
Insertion of the PML Gene Into the RAR{alpha} Locus},
journal = {Am J Clin Pathol},
year = {2009},
volume = {131},
pages = {64--71},
number = {1},
month = jan,
abstract = {Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia.
Submicroscopic insertion of RAR{alpha} into PML, resulting in PML-RAR{alpha}
from derivative chromosome 15, has been rarely reported. Herein,
we describe a functional PML-RAR{alpha} transcript from the long
arm of derivative chromosome 17 in a patient with microgranular APL.
The conventional karyotype showed normal chromosomes 15 and 17. It
is interesting that interphase and metaphase fluorescence in situ
hybridizations demonstrated a fusion signal on the long arm of one
chromosome 17 homolog, with both PML and RAR{alpha} still present
on chromosomes 15 and 17, respectively, although the signal on one
chromosome 15 was weaker, indicating partial loss of the PML gene.
Reverse transcriptase-polymerase chain reaction revealed a transcript
corresponding to a break cluster region 3 (bcr3) short form PML-RAR{alpha}.
To the best of our knowledge, this is the first report of an APL
with a bcr3/short form PML-RAR{alpha} transcript generated from derivative
chromosome 17 due to submicroscopic insertion of the PML gene into
the RAR{alpha} locus.},
url = {http://ajcp.ascpjournals.org/cgi/content/abstract/131/1/64}
}
@ARTICLE{Wang2008b,
author = {Wang, Junjun and Chen, Lixiang and Li, Peng and Li, Xilong and Zhou,
Huaijun and Wang, Fenglai and Li, Defa and Yin, Yulong and Wu, Guoyao},
title = {Gene Expression Is Altered in Piglet Small Intestine by Weaning and
Dietary Glutamine Supplementation},
journal = {J. Nutr.},
year = {2008},
volume = {138},
pages = {1025--1032},
number = {6},
month = jun,
abstract = {Dietary supplementation of glutamine prevents intestinal dysfunction
and atrophy in weanling piglets, but the underlying mechanism(s)
are largely unknown. This study was conducted to test the hypothesis
that weaning or glutamine may modulate expression of genes that are
crucial for intestinal metabolism and function. In Expt. 1, we obtained
small intestine from 28-d-old pigs weaned at 21 d of age and from
age-matched suckling piglets. In Expt. 2, piglets were weaned at
21 d of age and then had free access to diets supplemented with 1%
L-glutamine (wt:wt) or isonitrogenous L-alanine (control). At d 28,
we collected small intestine for biochemical and morphological measurements
and microarray analysis of gene expression using the Operon Porcine
Genome Oligo set. Early weaning resulted in increased (52-346%) expression
of genes related to oxidative stress and immune activation but decreased
(35-77%) expression of genes related to macronutrient metabolism
and cell proliferation in the gut. Dietary glutamine supplementation
increased intestinal expression (120-124%) of genes that are necessary
for cell growth and removal of oxidants, while reducing (34-75%)
expression of genes that promote oxidative stress and immune activation.
Functionally, the glutamine treatment enhanced intestinal oxidative-defense
capacity (indicated by a 29% increase in glutathione concentration),
prevented jejunal atrophy, and promoted small intestine growth (+12%)
and body weight gain (+19%) in weaned piglets. These findings reveal
coordinate alterations of gene expression in response to weaning
and aid in providing molecular mechanisms for the beneficial effect
of dietary glutamine supplementation to improve nutrition status
in young mammals.},
url = {http://jn.nutrition.org/cgi/content/abstract/138/6/1025}
}
@ARTICLE{Wang2008c,
author = {Wang, Jianyong and Duhart, Helen M. and Xu, Zengjun and Patterson,
Tucker A. and Newport, Glenn D. and Ali, Syed F.},
title = {Comparison of the time courses of selective gene expression and dopaminergic
depletion induced by MPP+ in MN9D cells},
journal = {Neurochemistry International},
year = {2008},
volume = {52},
pages = {1037--1043},
number = {6},
month = may,
abstract = {Parkinson's disease (PD) is a common neurodegenerative disease characterized
by progressive loss of midbrain dopaminergic neurons with unknown
etiology. MPP+ (1-methyl-4-phenylpyridinium ion) is the active metabolite
of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),
which induces Parkinson's-like symptoms in humans and animals. MPTP/MPP+
produces selective dopaminergic neuronal degeneration, therefore,
these agents are commonly used to study the pathogenesis of PD. However,
the mechanisms of their toxicity have not been fully elucidated.
Recently, we reported in a microarray study using a midbrain-derived
dopaminergic neuronal cell line, MN9D, that MPP+ induced significant
changes in a number of genes known to be associated with the dopaminergic
system. In this study, we investigated the expression time courses
of six genes using real-time RT-PCR, and compared them with the progressive
dopaminergic depletion caused by MPP+. Our data showed that dopamine
content was significantly decreased after 0.5 h of MPP+ (200 [mu]M)
exposure and was completely depleted after 40 h. The expression of
Gpr37, which is closely related to the pathogenesis of autosomal
recessive juvenile Parkinsonism, was up-regulated after 0.5 h, and
stayed up-regulated up to 48 h. Txnip, which is critical to the adjustment
of cellular redox status, was down-regulated after 1 h and stayed
down-regulated up to 48 h. Ldh1 and Cdo1, which are also involved
in oxidative stress, were down-regulated after 16 h and stayed down-regulated
up to 48 h. Two pro-apoptotic genes, Egln3 and Bnip3, were down-regulated
after 2 and 4 h, and stayed down-regulated up to 48 h. These findings
suggested that the time course of expression for multiple genes correlated
with the dopaminergic depletion; and MPP+-induced neurotoxicity in
MN9D cells could be used as a model to further explore the roles
of these and other genes in the pathogenesis and possible treatment
of PD.},
issn = {0197-0186},
keywords = {MPP+, MN9D cells, Time course, Gene expression, Dopamine, Neurotoxicity,
Parkinson's disease},
url = {http://www.sciencedirect.com/science/article/B6T0B-4R295WY-1/2/9d3d1e2ec537a08cfdc259fdf0fec9fb}
}
@ARTICLE{Wang2011n,
author = {Wang, Junwen and Jiang, Hui and Ji, Guanyu and Gao, Fei and Wu, Mingzhi
and Sun, Jihua and Luo, Huijuan and Wu, Jinghua and Wu, Renhua and
Zhang, Xiuqing},
title = {High resolution profiling of human exon methylation by liquid hybridization
capture-based bisulfite sequencing},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {597},
number = {1},
abstract = {BACKGROUND:DNA methylation plays important roles in gene regulation
during both normal developmental and disease states. In the past
decade, a number of methods have been developed and applied to characterize
the genome-wide distribution of DNA methylation. Most of these methods
endeavored to screen whole genome and turned to be enormously costly
and time consuming for studies of the complex mammalian genome. Thus,
they are not practical for studying multiple clinical samples in
biomarker research.RESULTS:Here, we display a novel strategy that
relies on the selective capture of target regions by liquid hybridization
followed by bisulfite conversion and deep sequencing, which is referred
to as liquid hybridization capture-based bisulfite sequencing (LHC-BS).
To estimate this method, we utilized about 2ug of native genomic
DNA from YanHuang (YH) whole blood samples and a mature dendritic
cell (mDC) line, respectively, to evaluate their methylation statuses
of target regions of exome. The results indicated that the LHC-BS
system was able to cover more than 97% of the exome regions and detect
their methylation statuses with acceptable allele dropouts. Most
of the regions that couldn't provide accurate methylation information
were distributed in chromosomes 6 and Y because of multiple mapping
to those regions. The accuracy of this strategy was evaluated by
pair-wise comparisons using the results from whole genome bisulfite
sequencing and validated by bisulfite specific PCR sequencing.CONCLUSIONS:In
the present study, we employed a liquid hybridisation capture system
to enrich for exon regions and then combined with bisulfite sequencing
to examine the methylation statuses for the first time. This technique
is highly sensitive and flexible and can be applied to identify differentially
methylated regions (DMRs) at specific genomic locations of interest,
such as within regulatory elements or promoters.},
url = {http://www.biomedcentral.com/1471-2164/12/597}
}
@ARTICLE{Wang2005c,
author = {Wang, Junfeng and Kilic, Gamze and Aydin, Muge and Burke, Zoe and
Oliver, Guillermo and Sosa-Pineda, Beatriz},
title = {Prox1 activity controls pancreas morphogenesis and participates in
the production of "secondary transition" pancreatic endocrine cells},
journal = {Developmental Biology},
year = {2005},
volume = {286},
pages = {182--194},
number = {1},
month = oct,
abstract = {The development of the mammalian pancreas is governed by various signaling
processes and by a cascade of gene activation events controlled by
different transcription factors. Here we show that the divergent
homeodomain transcription factor Prox1 is a novel, crucial regulator
of mouse pancreas organogenesis. Loss of Prox1 function severely
disrupted epithelial pancreas morphology and hindered pancreatic
growth without affecting significantly the genesis of endocrine cells
before E11.5. Conversely, the lack of Prox1 activity substantially
decreased the formation of islet cell precursors after E13.5, during
a period known as the "secondary transition". Notably, this defect
occurred concurrently with an abnormal increment of exocrine cells.
Hence, it is possible that Prox1 contributes to the allocation of
an adequate supply of islet cells throughout pancreas ontogeny by
preventing exocrine cell differentiation of multipotent pancreatic
progenitors. Prox1 thus appears to be an essential component of a
genetic program destined to produce the cellular complexity of the
mammalian pancreas.},
issn = {0012-1606},
keywords = {Pancreas, Prox1, Mouse, Endocrine, Exocrine, Development, Ontogeny,
Embryo, Cholecystokinin},
url = {http://www.sciencedirect.com/science/article/B6WDG-4GY8971-5/2/c44fd34f86c5a6e7f6a418f2f2a22200}
}
@ARTICLE{Wang2009g,
author = {Wang, Jun and Lindholm, Joliene R. and Willis, David K. and Orth,
Anthony and Goodman, Walter G.},
title = {Juvenile hormone regulation of Drosophila Epac--A guanine nucleotide
exchange factor},
journal = {Molecular and Cellular Endocrinology},
year = {2009},
volume = {305},
pages = {30--37},
number = {1-2},
month = jun,
abstract = {Real-time quantitative reverse transcription polymerase chain reaction
(qRT-PCR) was used to characterize the effects of juvenile hormone
(JH) on Epac (Exchange Protein directly Activated by Cyclic AMP;
NM_001103732), a guanine nucleotide exchange factor for Rap1 in Drosophila
S2 cells. JH treatment led to a rapid, dose-dependent increase in
Epac relative expression ratio (RER) when compared to treatment with
methyl linoleate (MLA) that lacks biological activity. The minimal
level of hormone needed to elicit a response was 100 ng/ml. Time-course
studies indicated a significant rise in the RER 1 h after treatment.
S2 cells were challenged with 20-hydroxyecdysone and a series of
compounds similar in structure to JH to determine the specificity
of the response. Methoprene and JH III displayed the greatest increases
in RER. Late third instar (96 h) Drosophila were exposed to diet
containing methoprene (500 ng/g diet); significantly higher RERs
for Epac were observed 12 h after exposure. JH had no effect on Epac
RERs in the human cell line HEK-293.},
issn = {0303-7207},
keywords = {Quantitative real-time RT-PCR, Epac, GEF, JH, Methoprene, Methyl farnesoate,
Bisepoxy JH III, 20-Hydroxyecdysone},
url = {http://www.sciencedirect.com/science/article/B6T3G-4VNK6BS-1/2/a4dfc4e92c8bf11fbe25d7c84712a9c3}
}
@ARTICLE{Wang2005d,
author = {Wang, Jin and Nguyen, Vu and Glen, Jacqueline and Henderson, Brian
and Saul, Allan and Miller, Louis H.},
title = {Improved yield of recombinant merozoite Surface protein 3 (MSP3)
from Pichia pastoris using chemically defined media},
journal = {Biotechnol. Bioeng.},
year = {2005},
volume = {90},
pages = {838--847},
number = {7},
abstract = {Abstract 10.1002/bit.20491.abs Plasmodium falciparum merozoite surface
protein 3 (MSP3) is a leading blood-stage malaria vaccine candidate.
Vaccination with Pichia pastoris derived recombinant MSP3 protected
Aotus nacymai monkeys from the parasite's lethal challenge and the
post-challenge antibody titer against MSP3 correlated with protection.
In our preliminary attempts to produce this vaccine in fermentors,
little or no expression of MSP3 was observed in chemically defined
media, although the same P. pastoris strain produced MSP3 in complex
media. Our goal is to develop a Phase I/II clinical manufacturing
process in completely chemically defined media because of the concern
of potential prion contamination in complex media containing animal
derived products. Here, we report our investigations into various
factors to improve the yield of MSP3 in defined media. We found that
an induction pH (pHi) 6.8 yielded MSP3 at 434 mg/L whereas there
was no product at pHi≤ 5, though cell growth was the same in
all pHi levels examined. High levels of NH 4+ consumed at pHi 6.8
were directly correlated to the enhanced MSP3 production. Furthermore,
an additional 3.5-fold increase in the yield of MSP3 was obtained
by addition of casamino acids at pHi 6.8. No direct correlation was
observed between protease activity in the culture supernatants and
lack of MSP3 expression. Neither high P. pastoris biomass generated
at a high specific growth rate (0.04/h) nor low induction temperatures
during induction improved yield. Nitrogen source was the most important
factor affecting expression of MSP3 in defined media. Published 2005
Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {malaria, Plasmodium falciparum, merozoite surface protein 3, Pichia
pastoris, chemically defined media, nitrogen source},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.20491}
}
@ARTICLE{Wang2011w,
author = {Wang, J. and Qiu, J. and Dong, J. and Li, H. and Luo, M. and Dai,
X. and Zhang, Y. and Leng, B. and Niu, X. and Zhao, S. and Deng,
X.},
title = {Chrysin protects mice from Staphylococcus aureus pneumonia},
journal = {Journal of Applied Microbiology},
year = {2011},
volume = {111},
pages = {1551--1558},
number = {6},
abstract = {Aim:  To elucidate the effect of chrysin on α-haemolysin production
by Staphylococcus aureus and protection against pneumonia in a murine
model.Methods and Results:  Haemolysis, Western blot and real-time
RT-PCR assays were performed to evaluate the effect of chrysin on
α-haemolysin secretion by Staph. aureus. The efficacy of chrysin
against human alveolar epithelial cell injury by α-haemolysin was
tested using live/dead staining or by measuring lactate dehydrogenase
activity. Furthermore, we determined the protective effect of chrysin
against Staph. aureus pneumonia through histopathology experiments
in a mouse model. The production of α-haemolysin by Staph. aureus
was inhibited when presented with an increasing subinhibitory concentration
of chrysin in vitro. Consistent with this result, chrysin prevented
α-haemolysin-mediated cell injury and protected mice from Staph. aureus
pneumonia.Conclusions:  Chrysin is a potent inhibitor of α-haemolysin
expression by Staph. aureus, and it conferred a significant degree
of protection against Staph. aureus pneumonia.Significance and Impact
of Study:  The chrysin-mediated inhibition of α-haemolysin production
and protection against Staph. aureus pneumonia may offer a new strategy
in combating pathogen infections.},
doi = {10.1111/j.1365-2672.2011.05170.x},
issn = {1365-2672},
keywords = {anti-virulence, chrysin, pneumonia, Staphylococcus aureus, α-haemolysin},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2672.2011.05170.x}
}
@ARTICLE{Wang2009h,
author = {Wang, Jianyong and Rahman, Mohammed F. and Duhart, Helen M. and Newport,
Glenn D. and Patterson, Tucker A. and Murdock, Richard C. and Hussain,
Saber M. and Schlager, John J. and Ali, Syed F.},
title = {Expression changes of dopaminergic system-related genes in PC12 cells
induced by manganese, silver, or copper nanoparticles},
journal = {NeuroToxicology},
year = {2009},
volume = {30},
pages = {926--933},
number = {6},
month = nov,
abstract = {Nanoparticles have received a great deal of attention for producing
new engineering applications due to their novel physicochemical characteristics.
However, the broad application of nanomaterials has also produced
concern for nanoparticle toxicity due to increased exposure from
large-scale industry production. This study was conducted to investigate
the potential neurotoxicity of manganese (Mn), silver (Ag), and copper
(Cu) nanoparticles using the dopaminergic neuronal cell line, PC12.
Selective genes associated with the dopaminergic system were investigated
for expression changes and their correlation with dopamine depletion.
PC12 cells were treated with 10 [mu]g/ml Mn-40 nm, Ag-15 nm, or Cu-90 nm
nanoparticles for 24 h. Cu-90 nanoparticles induced dopamine depletion
in PC12 cells, which is similar to the effect induced by Mn-40 shown
in a previous study. The expression of 11 genes associated with the
dopaminergic system was examined using real-time RT-PCR. The expression
of Txnrd1 was up-regulated after the Cu-90 treatment and the expression
of Gpx1 was down-regulated after Ag-15 or Cu-90 treatment. These
alterations are consistent with the oxidative stress induced by metal
nanoparticles. Mn-40 induced a down-regulation of the expression
of Th; Cu-90 induced an up-regulation of the expression of Maoa.
This indicates that besides the oxidation mechanism, enzymatic alterations
may also play important roles in the induced dopamine depletion.
Mn-40 also induced a down-regulation of the expression of Park2;
while the expression of Snca was up-regulated after Mn-40 or Cu-90
treatment. These data suggest that Mn and Cu nanoparticles-induced
dopaminergic neurotoxicity may share some common mechanisms associated
with neurodegeneration.},
booktitle = {10th International Symposium on Neurobehavioral Methods and Effects
in Environmental and Occupational Health},
issn = {0161-813X},
keywords = {Manganese, Silver, Copper, Nanoparticles, Dopamine, Neurotoxicity,
Gene expression, PC 12 cells},
url = {http://www.sciencedirect.com/science/article/B6W81-4X97CT6-1/2/d1097831985b4be8318649fca036c900}
}
@ARTICLE{Wang2012,
author = {Jing Wang and Anton Razuvaev and Lasse Folkersen and Erika Hedin
and Joy Roy and Kerstin Brismar and Ulf Hedin},
title = {The expression of IGFs and IGF binding proteins in human carotid
atherosclerosis, and the possible role of IGF binding protein-1 in
the regulation of smooth muscle cell proliferation},
journal = {Atherosclerosis},
year = {2012},
volume = {220},
pages = {102 - 109},
number = {1},
abstract = {Objective Proliferation of smooth muscle cells (SMCs) in the fibrous
cap of atherosclerotic lesions has been proposed to be important
for plaque stability. Since the insulin-like growth factor (IGF)
system has been implicated to play a role in atherosclerosis and
plaque stability, we investigated the expression of members of the
IGF system in carotid plaques, in particular IGFBP-1 and its role
in the regulation of SMC proliferation. Methods and results Gene
expression profiles of the IGF system in 164 human carotid plaques
obtained from our Biobank of Karolinska Endarterectomies (BiKE) were
analyzed. Expression of IGFBP-1 mRNA was significantly increased
in carotid plaques compared with normal iliac arteries in contrast
to IGF-1, IGF-2, and IGFBP-3 to IGFBP-6. The expression of IGFBP-1
mRNA correlated positively to that of CD163, CD68, IL-1β, IL-6,
TNFα, IGFBP-4 and IGFBP-5. Immunohistochemistry demonstrated co-localization
of IGFBP-1 with SMCs and macrophages. In vitro studies showed that
IL-1β, IL-6 and TNFα stimulated IGFBP-1 mRNA expression in SMCs.
IGFBP-1 stimulated SMC proliferation through ERK1/2 activation but
independently of the IGF-1 receptor. In addition, IGFBP-1 modulated
the effect of IGF-1 on SMC proliferation and ERK1/2 activation. Conclusions
Our results demonstrate that IGFBP-1 mRNA and protein is detected
at increased levels in human carotid plaques, possibly as a consequence
of plaque inflammation. IGFBP-1 affects SMC proliferation and may
be involved in the regulation of plaque stability.},
doi = {10.1016/j.atherosclerosis.2011.10.032},
issn = {0021-9150},
keywords = {IGF},
url = {http://www.sciencedirect.com/science/article/pii/S0021915011010227}
}
@ARTICLE{Wang2004b,
author = {Wang, Jian and Robinson, John F. and Khan, Hafiz M. R. and Carter,
David E. and McKinney, James and Miskie, Brooke A. and Hegele, Robert
A.},
title = {Optimizing RNA extraction yield from whole blood for microarray gene
expression analysis},
journal = {Clinical Biochemistry},
year = {2004},
volume = {37},
pages = {741--744},
number = {9},
month = sep,
abstract = {Objectives: Microarray analysis of gene expression profiles of blood
leukocytes has many potential clinical and research applications.
Design and methods: We used the PAXgene Blood RNA System to prepare
RNA from the whole blood of normal volunteers using two incubation
times followed by gene expression profiling using the Affymetrix
HU133A GeneChip. Conclusions: Longer incubation gave a significantly
higher RNA yield and samples that were satisfactory for microarray
analysis, with excellent pairwise correlations between replicates.},
issn = {0009-9120},
keywords = {Molecular diagnosis, Gene expression, Immunology, Epidemiology, Metabolic
disease},
url = {http://www.sciencedirect.com/science/article/B6TDD-4C82NSR-1/2/964890fb19fb4bcce65939e3dd88315b}
}
@ARTICLE{Wang2006,
author = {Wang, Jieru and Wang, Shuanglin and Manzer, Rizwan and McConville,
Glen and Mason, Robert J.},
title = {Ozone induces oxidative stress in rat alveolar type II and type I-like
cells},
journal = {Free Radical Biology and Medicine},
year = {2006},
volume = {40},
pages = {1914--1928},
number = {11},
month = jun,
abstract = {Ozone is a highly reactive gas present in urban air, which penetrates
deep into the lung and causes lung injury. The alveolar epithelial
cells are among the first cell barriers encountered by ozone. To
define the molecular basis of the cellular response to ozone, primary
cultures of rat alveolar type II and type I-like cells were exposed
to 100 ppb ozone or air for 1 h. The mRNA from both phenotypes was
collected at 4 and 24 h after exposure for gene expression profiling.
Ozone produced extensive alterations in gene expression involved
in stress and inflammatory responses, transcription factors, antioxidant
defenses, extracellular matrix, fluid transport, and enzymes of lipid
metabolism and cell differentiation. Real-time reverse transcription-polymerase
chain reaction and Western blot analysis verified changes in mRNA
and protein levels of selected genes. Besides the increased stress
response, ozone exposure downregulated genes of cellular differentiation.
The changes were more prominent at 4 h in the type I-like phenotype
and at 24 h in the type II phenotype. The type I-like cells were
more sensitive to ozone than type II cells. The genome-wide changes
observed provide insight into signal pathways activated by ozone
and how cellular protection mechanisms are initiated.},
issn = {0891-5849},
keywords = {Alveolar epithelium, Microarray analyses, Oxidative stress, Differentiation,
Free radical},
url = {http://www.sciencedirect.com/science/article/B6T38-4J78WXS-1/2/43c00df55d54715624537e81e7076a69}
}
@ARTICLE{Wang2004c,
author = {Wang, Jinzhao and Wei, Qingqing and Wang, Cong-Yi and Hill, William
D. and Hess, David C. and Dong, Zheng},
title = {Minocycline Up-regulates Bcl-2 and Protects against Cell Death in
Mitochondria},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {19948--19954},
number = {19},
month = may,
abstract = {Robust neuroprotective effects have been shown for minocycline. Whether
it also protects nonneuronal cells or tissues is unknown. More importantly,
the mechanisms of minocylcine protection appear multifaceted and
remain to be clarified. Here we show that minocycline can protect
kidney epithelial cells in vitro and protect the kidneys from ischemic
injury in vivo. We further show that Bcl-2 is a key molecular determinant
of minocycline protection. Minocycline protected kidney epithelial
cells against apoptosis induced by hypoxia, azide, cisplatin, and
staurosporine. The protection occurred at mitochondria, involving
the suppression of Bax accumulation, outer membrane damage, and cytochrome
c release. Minocycline induced Bcl-2, which accumulated in mitochondria
and interacted with death-promoting molecules including Bax, Bak,
and Bid. Down-regulation of Bcl-2 by specific antisense oligonucleotides
abolished the cytoprotective effects of minocycline. Thus, minocycline
can protect neuronal as well as nonneuronal cells and tissues. One
mechanism for minocycline protection involves the induction of Bcl-2,
an antiapoptotic protein.},
url = {http://www.jbc.org/cgi/content/abstract/279/19/19948}
}
@ARTICLE{Wang2007b,
author = {Wang, Jianyong and Xu, Zengjun and Fang, Hong and Duhart, Helen M.
and Patterson, Tucker A. and Ali, Syed F.},
title = {Gene expression profiling of MPP+-treated MN9D cells: A mechanism
of toxicity study},
journal = {NeuroToxicology},
year = {2007},
volume = {28},
pages = {979--987},
number = {5},
month = sep,
abstract = {Parkinson's disease (PD) is a common neurodegenerative disease characterized
by progressive loss of midbrain dopaminergic neurons with unknown
etiology. MPP+ (1-methyl-4-phenylpyridinium) is the active metabolite
of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),
which induces Parkinson's-like syndromes in humans and animals. MPTP/MPP+
treatment produces selective dopaminergic neuronal degeneration,
therefore, these agents are commonly used to study the pathogenesis
of PD. However, the mechanisms of their toxicity have not been elucidated.
In order to gain insights into MPP+-induced neurotoxicity, a gene
expression microarray study was performed using a midbrain-derived
dopaminergic neuronal cell line, MN9D. Utilizing a two-color reference
design, Agilent mouse oligonucleotide microarrays were used to examine
relative gene expression changes in MN9D cells treated with 40 [mu]M
MPP+ compared with controls. Bioinformatics tools were used for data
evaluation. Briefly, raw data were imported into the NCTR ArrayTrack
database, normalized using a Lowess method and data quality was assessed.
The Student's t-test was used to determine significant changes in
gene expression (set as p < 0.05, fold change >1.5). Gene Ontology
for Function Analysis (GOFFA) and Ingenuity Pathway Analysis were
employed to analyze the functions and roles of significant genes
in biological processes. Of the 51 significant genes identified,
44 were present in the GOFFA or Ingenuity database. These data indicate
that multiple pathways are involved in the underlying mechanisms
of MPP+-induced neurotoxicity, including apoptosis, oxidative stress,
iron binding, cellular metabolism, and signal transduction. These
data also indicate that MPP+-induced toxicity shares common molecular
mechanisms with the pathogenesis of PD and further pathway analyses
will be conducted to explore these mechanisms.},
booktitle = {Twenty-Third International Neurotoxicology Conference: "Neurotoxicity
in Development and Aging"},
issn = {0161-813X},
keywords = {MPP+, MN9D cells, Microarray, Gene expression, Neurotoxicity, Parkinson's
disease},
url = {http://www.sciencedirect.com/science/article/B6W81-4N7SBJP-1/2/a12e673536cdb789fda47a64062bfc83}
}
@ARTICLE{Wang2012d,
author = {Jicheng Wang and Wenyi Zhang and Zhi Zhong and Aibin Wei and Qiuhua
Bao and Yong Zhang and Tiansong Sun and Andrew Postnikoff and He
Meng and Heping Zhang},
title = {Gene expression profile of probiotic Lactobacillus casei Zhang during
the late stage of milk fermentation},
journal = {Food Control},
year = {2012},
volume = {25},
pages = {321 - 327},
number = {1},
abstract = {Lactobacillus casei Zhang is a new probiotic strain isolated from
koumiss in Inner Mongolia of China, which has been commercially used
as starter in the manufacture of dairy products. To study gene expression
profile of L. casei Zhang during growth in milk, a whole-genome microarray
was used. Compared to L. casei Zhang grown to the late logarithmic
phase in milk, 61 genes were significantly up-regulated (>5 fold)
in the stationary phase, whereas 26 genes were down-regulated. Collectively,
these data showed that the majority of the identified genes were
involved in carbohydrate metabolism and energy production, followed
by genes involved in nucleotide metabolism, inorganic ion transport,
amino acid transport and metabolism, chaperones, etc. This study
demonstrates the fundamental effects of cultural conditions on the
transcriptome of L. casei Zhang. Moreover, it improves the understanding
of growth and survival mechanism of the bacterium during the late
stage of milk fermentation.},
doi = {10.1016/j.foodcont.2011.10.036},
issn = {0956-7135},
keywords = {Probiotics},
url = {http://www.sciencedirect.com/science/article/pii/S0956713511004403}
}
@ARTICLE{Wang2011u,
author = {Wang, Jiangxin and Zhu, Xiaoshan and Zhang, Xuezhi and Zhao, Zheng
and Liu, Huan and George, Rajani and Wilson-Rawls, Jeanne and Chang,
Yung and Chen, Yongsheng},
title = {Disruption of zebrafish (Danio rerio) reproduction upon chronic exposure
to TiO2 nanoparticles},
journal = {Chemosphere},
year = {2011},
volume = {83},
pages = {461--467},
number = {4},
month = apr,
abstract = {As common engineered nanomaterials, TiO2 nanoparticles (nTiO2) are
usually perceived as non-toxic, and have already been widely used
in many products and applications. Such a perception might have been
shaped by some short-term studies that revealed no/low toxicity of
nTiO2 to cells and eco-relevant organisms. However, given the ultimate
release of nTiO2 into the aquatic environment, which can act as a
sink for engineered nanoparticles, their long-term impact on the
environment and human health is still a concern and deserves more
research efforts. Here, for the first time, we demonstrate that chronic
exposure of zebrafish to 0.1 mg L-1 nTiO2, can significantly impair
zebrafish reproduction. For instance, there was a 29.5% reduction
in the cumulative number of zebrafish eggs after 13 weeks of nTiO2
exposure. Thus, we provided timely information on indicating a serious
risk of reproductive impairment of environments contaminated with
low levels of nTiO2 on aquatic organisms, leading to alterations
in population dynamics and aquatic ecosystem balance, and thus warrants
a careful scrutiny on toxicity assessment of nTiO2, especially their
long-term impact.},
issn = {0045-6535},
keywords = {Acute toxicity, Bioaccumulation, Chronic toxicity, Microarry, Reproduction,
Zebrafish, TiO2, Nanoparticles},
url = {http://www.sciencedirect.com/science/article/pii/S0045653510014748}
}
@ARTICLE{Wang2010c,
author = {Wang, Ke and Xiang, Xiao-Hui and He, Fei and Lin, Li-Bo and Zhang,
Rong and Ping, Xing-Jie and Han, Ji-Sheng and Guo, Ning and Zhang,
Qing-Hua and Cui, Cai-Lian and Zhao, Guo-Ping},
title = {Transcriptome profiling analysis reveals region-distinctive changes
of gene expression in the CNS in response to different moderate restraint
stress},
journal = {Journal of Neurochemistry},
year = {2010},
volume = {113},
pages = {1436--1446},
number = {6},
abstract = {J. Neurochem. (2010) 113, 1436–1446. Abstract It is generally believed
that temporary moderate stress to a living organism has protective
and adaptive effects, but little is known about the responses of
CNS to the moderate stresses at molecular level. This study aims
to investigate the gene expression changes induced by moderate stress
in CNS stress- and nociception-related regions of rats. Moderate
restraint was applied to rats for 50Â min and cDNA microarrays were
used to detect the differential gene expression in different CNS
regions. Transcriptome profiling analysis showed that at acute stage
stress-related genes were up-regulated in arcuate nucleus; fight-or-flight
behavior-related genes were up-regulated in periaqueductal gray,
while nitric oxide and GABA signal transmission-related genes were
up-regulated in spinal dorsal horn. In addition, immune-related genes
were broadly regulated, especially at the late stage. These results
suggested that specific genes of certain gene ontology categories
were spatiotemporally regulated in specific CNS regions related to
relevant functions under moderate external stimuli at acute stage,
while immune response was broadly regulated at the late stage. The
co-regulated genes among the three different CNS regions may play
general roles in CNS when exposed to moderate stress. Furthermore,
these results will help to elucidate the physiological processes
involved in moderate stress in CNS.},
issn = {1471-4159},
keywords = {CNS, microarray, restraint, stress, transcriptome profile},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2010.06679.x}
}
@ARTICLE{Wang2009i,
author = {Wang, Kai and Zhang, Shile and Marzolf, Bruz and Troisch, Pamela
and Brightman, Amy and Hu, Zhiyuan and Hood, Leroy E. and Galas,
David J.},
title = {Circulating microRNAs, potential biomarkers for drug-induced liver
injury},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {4402--4407},
number = {11},
month = mar,
abstract = {Drug-induced liver injury is a frequent side effect of many drugs,
constitutes a significant threat to patient health and has an enormous
economic impact on health care expenditures. Numerous efforts have
been made to identify reliable and predictive markers to detect the
early signs of drug-induced injury to the liver, one of the most
vulnerable organs in the body. These studies have, however, not delivered
any more informative candidates than the serum aminotransferase markers
that have been available for {approx}30 years. Using acetaminophen
overdose-induced liver injury in the mouse as a model system, we
have observed highly significant differences in the spectrum and
levels of microRNAs in both liver tissues and in plasma between control
and overdosed animals. Based on our survey of microRNA expression
among normal tissues, some of the microRNAs, like messenger RNAs,
display restricted tissue distributions. A number of elevated circulating
microRNAs in plasma collected from acetaminophen-overdosed animals
are highly expressed in the liver. We have demonstrated that specific
microRNA species, such as mir-122 and mir-192, both are enriched
in the liver tissue and exhibit dose- and exposure duration-dependent
changes in the plasma that parallel serum aminotransferase levels
and the histopathology of liver degeneration, but their changes can
be detected significantly earlier. These findings suggest the potential
of using specific circulating microRNAs as sensitive and informative
biomarkers for drug-induced liver injury.},
url = {http://www.pnas.org/cgi/content/abstract/106/11/4402}
}
@ARTICLE{Wang2003,
author = {Wang, Lin and Hoque, Ashraful and Luo, Robert Z. and Yuan, Jiuhong
and Lu, Zhen and Nishimoto, Arata and Liu, Jinsong and Sahin, Aysegul
A. and Lippman, Scott M. and Bast, Robert C., Jr. and Yu, Yinhua},
title = {Loss of the Expression of the Tumor Suppressor Gene ARHI Is Associated
with Progression of Breast Cancer},
journal = {Clin. Cancer Res.},
year = {2003},
volume = {9},
pages = {3660--3666},
number = {10},
month = sep,
abstract = {Purpose: Ductal carcinoma in situ (DCIS) is a preinvasive-stage breast
carcinogenesis that accounts for [~]20[~]25% of mammographically
detected breast cancers. A significant fraction of untreated DCIS
will evolve into invasive cancer. ras homologue I (ARHI) is an imprinted
tumor suppressor gene that is expressed in normal breast epithelial
cells but absent or down-regulated in breast cancer cells. This study
investigated the relationship of ARHI expression to the progression
of breast cancer. Experimental Design: We analyzed ARHI expression
in DCIS, invasive breast carcinoma, and adjacent normal breast epithelium
from 64 formalin-fixed, paraffin-embedded DCIS specimens by both
immunohistochemistry and in situ hybridization. We also analyzed
the correlation between ARHI expression and progression of breast
cancer, as well as the correlation of ARHI expression and cyclin
D1 and p21WAF1/CIP1 expression in DCIS. Results: Normal breast epithelium
was found in all of the specimens and invasive breast carcinoma was
found in 23 specimens. ARHI mRNA and protein were detected in all
of the normal breast epithelia. ARHI expression was detected mainly
in cytoplasm and rarely present in the nucleus. By histochemical
analysis, ARHI expression was down-regulated in 41% (26 of 64) of
DCIS and 70% (16 of 23) of invasive carcinomas comparing the specimens
with adjacent normal breast epithelium. When DCIS and invasive cancer
were present in the same sample, ARHI was further down-regulated
in 26% (6 of 23) of invasive carcinoma. In four cases [4 (17%) of
23] of invasive carcinoma, ARHI protein expression was totally lost.
Consistent results were obtained with an in situ hybridization assay
for ARHI at the mRNA level. Higher levels of expression of cyclin
D1 and p21WAF1/CIP1 were observed in DCIS than in the adjacent epithelia.
The expression of cyclin D1 and p21WAF1/CIP1 was inversely correlated
with that of ARHI. Conclusions: Our results indicate that ARHI expression
is markedly down-regulated in DCIS, and a further decrease in ARHI
expression is associated with progression of breast cancer.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/9/10/3660}
}
@ARTICLE{Wang2012c,
author = {Wang, Lu and Motoi, Toru and Khanin, Raya and Olshen, Adam and Mertens,
Fredrik and Bridge, Julia and Cin, Paola Dal and Antonescu, Cristina
R. and Singer, Samuel and Hameed, Meera and Bovee, Judith V.M.G.
and Hogendoorn, Pancras C. W. and Socci, Nicholas and Ladanyi, Marc},
title = {Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal
chondrosarcoma based on a genome-wide screen of exon-level expression
data},
journal = {Genes, Chromosomes and Cancer},
year = {2012},
volume = {51},
pages = {127--139},
number = {2},
abstract = {Cancer gene fusions that encode a chimeric protein are often characterized
by an intragenic discontinuity in the RNA\expression levels of the
exons that are 5′ or 3′ to the fusion point in one or both of
the fusion partners due to differences in the levels of activation
of their respective promoters. Based on this, we developed an unbiased,
genome-wide bioinformatic screen for gene fusions using Affymetrix
Exon array expression data. Using a training set of 46 samples with
different known gene fusions, we developed a data analysis pipeline,
the “Fusion Score (FS) model�, to score and rank genes for intragenic
changes in expression. In a separate discovery set of 41 tumor samples
with possible unknown gene fusions, the FS model generated a list
of 552 candidate genes. The transcription factor gene NCOA2 was one
of the candidates identified in a mesenchymal chondrosarcoma. A novel
HEY1-NCOA2 fusion was identified by 5′ RACE, representing an in-frame
fusion of HEY1 exon 4 to NCOA2 exon 13. RT-PCR or FISH evidence of
this HEY1-NCOA2 fusion was present in all additional mesenchymal
chondrosarcomas tested with a definitive histologic diagnosis and
adequate material for analysis (n = 9) but was absent in 15 samples
of other subtypes of chondrosarcomas. We also identified a NUP107-LGR5
fusion in a dedifferentiated liposarcoma but analysis of 17 additional
samples did not confirm it as a recurrent event in this sarcoma type.
The novel HEY1-NCOA2 fusion appears to be the defining and diagnostic
gene fusion in mesenchymal chondrosarcomas. © 2011 Wiley Periodicals,
Inc.},
doi = {10.1002/gcc.20937},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20937}
}
@ARTICLE{Wang2006a,
author = {Wang, Lu and Scheffler, Brian E. and Willett, Kristine L.},
title = {CYP1C1 Messenger RNA Expression is Inducible by Benzo[a]pyrene in
Fundulus heteroclitus Embryos and Adults},
journal = {Toxicol. Sci.},
year = {2006},
volume = {93},
pages = {331--340},
number = {2},
month = oct,
abstract = {CYP1C is the newest member of the CYP1 family of P450s; however, its
physiological significance, inducers, and metabolic functions are
unknown. Two full-length alleles of Fundulus heteroclitus CYP1C1
complementary DNA were cloned. The 529 amino acid protein shared
the highest amino acid identity with Stenotomus chrysops CYP1C1 (81%).
To investigate whether the carcinogen benzo[a]pyrene (BaP) was a
CYP1C1 inducer, we used real-time PCR to quantitatively measure tissue-
and sex-specific expression of both CYP1C1 and CYP1A messenger RNAs
(mRNAs) in BaP-exposed adult fish. CYP1C1 mRNA expression was constitutively
higher than CYP1A in brain, spleen, eye, and gonad, while CYP1A was
higher in gastrointestinal tract (GI), heart, gill, and liver. Kidney
had equal but high expression of both CYP1s. There were sex differences
in constitutive CYP1 expression in the GI, liver, gill, and eye.
BaP exposure caused induction of CYP1C1 expression in female and
male heart (31- and 17-fold), gill (seven- and four-fold), and liver
(six- and five-fold), respectively. Embryo CYP1 expression was constitutively
highest at 2 weeks posthatch, and whole embryos expressed 3- to 15-fold
more CYP1C1 mRNA compared to CYP1A. BaP, 10 {micro}g/l for 10 days,
caused induction of both genes at 120 and 240 h postfertilization.
Our results suggest that teleost CYP1C, in addition to CYP1A, is
inducible by BaP, has a broad tissue distribution, and should be
further investigated for its role in carcinogen bioactivation.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/93/2/331}
}
@ARTICLE{Wang2010q,
author = {Wang, Limin and Stegemann, Jan P.},
title = {Extraction of high quality RNA from polysaccharide matrices using
cetlytrimethylammonium bromide},
journal = {Biomaterials},
year = {2010},
volume = {31},
pages = {1612--1618},
number = {7},
month = mar,
abstract = {Polysaccharides are increasingly being used as biomaterials for tissue
engineering and regenerative medicine. Quantitative analysis of gene
expression from cells in three-dimensional (3D) scaffolds requires
extraction of messenger RNA, which is complicated in polysaccharide
materials by ionic complexing between nucleic acids and the matrix.
We used a strongly cationic surfactant, cetyltrimethylammonium bromide
(CTAB), to extract RNA from human mesenchymal stem cells embedded
in 3D chitosan, agarose and collagen matrices. CTAB extraction was
compared to conventional guanidinium thiocyanate-based methods for
RNA isolation by assessing RNA yield, purity (A260/A280 and A260/A230)
and integrity (28S/18S and RIN). For polysaccharide-based matrices,
CTAB extraction yielded significantly more RNA with higher purity
than guanidinium thiocyanate-based methods alone. The extracted RNA
was largely intact as indicated by 28S/18S ratios and RIN values,
while these parameters could not be measured using conventional kits
alone. For pure collagen matrices, the CTAB method was comparable
or better than guanidinium thiocyanate-based methods in terms of
RNA yield and quality. We further validated the CTAB protocol using
semi-quantitative and quantitative RT-PCR to amplify both large and
small amplicons. Our results show that the CTAB-based method is a
facile and effective way to extract abundant, high quality RNA from
polysaccharide and protein biomaterials.},
issn = {0142-9612},
keywords = {RNA, PCR, Polysaccharide, Tissue engineering, Chitosan, Collagen},
url = {http://www.sciencedirect.com/science/article/B6TWB-4XVB6WK-3/2/f2929f4cd264e72e91ab94165f7c99cf}
}
@ARTICLE{Wang2009j,
author = {Wang, Liang and Tang, Hui and Thayanithy, Venugopal and Subramanian,
Subbaya and Oberg, Ann L. and Cunningham, Julie M. and Cerhan, James
R. and Steer, Clifford J. and Thibodeau, Stephen N.},
title = {Gene Networks and microRNAs Implicated in Aggressive Prostate Cancer},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {9490--9497},
number = {24},
month = dec,
abstract = {Prostate cancer, a complex disease, can be relatively harmless or
extremely aggressive. To identify candidate genes involved in causal
pathways of aggressive prostate cancer, we implemented a systems
biology approach by combining differential expression analysis and
coexpression network analysis to evaluate transcriptional profiles
using lymphoblastoid cell lines from 62 prostate cancer patients
with aggressive phenotype (Gleason grade [≥] 8) and 63 prostate
cancer patients with nonaggressive phenotype (Gleason grade [≤]
5). From 13,935 mRNA genes and 273 microRNAs (miRNA) tested, we identified
significant differences in 1,100 mRNAs and 7 miRNAs with a false
discovery rate (FDR) of <0.01. We also identified a coexpression
module demonstrating significant association with the aggressive
phenotype of prostate cancer (P = 3.67 x 10-11). The module of interest
was characterized by overrepresentation of cell cycle-related genes
(FDR = 3.50 x 10-50). From this module, we further defined 20 hub
genes that were highly connected to other genes. Interestingly, 5
of the 7 differentially expressed miRNAs have been implicated in
cell cycle regulation and 2 (miR-145 and miR-331-3p) are predicted
to target 3 of the 20 hub genes. Ectopic expression of these two
miRNAs reduced expression of target hub genes and subsequently resulted
in cell growth inhibition and apoptosis. These results suggest that
cell cycle is likely to be a molecular pathway causing aggressive
phenotype of prostate cancer. Further characterization of cell cycle-related
genes (particularly, the hub genes) and miRNAs that regulate these
hub genes could facilitate identification of candidate genes responsible
for the aggressive phenotype and lead to a better understanding of
prostate cancer etiology and progression. [Cancer Res 2009;69(24):9490-7]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/24/9490}
}
@ARTICLE{Wang2011s,
author = {Wang, Liying and Zhou, Caixiu and Wang, Zhong and Liu, Jun and Jing,
Zhiwei and Zhang, Zhanjun and Wang, Yongyan},
title = {Dynamic variation of genes profiles and pathways in the hippocampus
of ischemic mice: A genomic study},
journal = {Brain Research},
year = {2011},
volume = {1372},
pages = {13--21},
month = feb,
abstract = {Objective To reveal the potential time-sequential molecular mechanism
in the hippocampus of ischemia-reperfusion mice, so as to provide
pertinent evidence for differential treatment during different phases
after cerebral ischemia-reperfusion injury. Methods Seventy-five
male Kunming mice were randomly divided into four groups: sham, ischemia
and reperfusion for 3 h, 12 h, and 24 h, respectively. A cDNA microarray
involving 374 cDNA ischemia-related genes, selected from the Science
STKE database, was performed to detect the gene expression profiles.
All data analyses were performed in the FDA ArrayTrack system. Data
were also uploaded to the KEGG database (http://www.genome.jp/kegg/)
to analyze the genetic pathways. Results Clustering and principal
component analyses showed clear boundaries in the differentially
expressed genes among the 3 h, 12 h, and 24 h groups. Although 56
overlapping up-regulated genes and 2 down-regulated genes were identified
in 3 h, 12 h, and 24 h groups, the sequence variation of CA1 neurons
and gene expression profiles also existed in all groups. Based on
the total number of altered genes, the top 3 GO categories were metabolism,
signal and cell cycle, which shared 8, 11 and 5 overlapping genes
in 3 h, 12 h, and 24 h groups, respectively. As for metabolism, there
were 2 specific altered genes in the 3 h group (casp8ap2 and mmp2),
6 in the 24 h group (daxx, gadd45a, adamts1, adcy8, cyp51, dusp16),
but none in the 12 h group. Based on the KEGG database analysis,
18 overlapping pathways were detected in the three groups; and 1,
12 and 2 overlapping pathways were noted between the 3 h and 12 h,
12 h and 24 h, and 3 h and 24 h comparisons, respectively. The gene
expressions of Caspase 2 and Rgs6 were identified by real-time RT-PCR,
which was consistent with the results of microarray analysis. Conclusion
Overlapping and variable genes and pathways demonstrate the time-sequential
molecular mechanism in the hippocampus of ischemic mice, which may
provide evidence for rational treatment during different phases after
cerebral ischemia-reperfusion injury.},
issn = {0006-8993},
keywords = {Cerebral ischemia-reperfusion, Dynamic variation, Gene profile, Pathway,
Genomic},
url = {http://www.sciencedirect.com/science/article/pii/S0006899310026144}
}
@ARTICLE{Wang2008d,
author = {Wang, L. M. and Schroeder, A. and Loh, D. and Smith, D. and Lin,
K. and Han, J. H. and Michel, S. and Hummer, D. L. and Ehlen, J.
C. and Albers, H. E. and Colwell, C. S.},
title = {Role for the NR2B subunit of the N-methyl-d-aspartate receptor in
mediating light input to the circadian system},
journal = {European Journal of Neuroscience},
year = {2008},
volume = {27},
pages = {1771--1779},
number = {7},
abstract = {Abstract Light information reaches the suprachiasmatic nucleus (SCN)
through a subpopulation of retinal ganglion cells that utilize glutamate
as a neurotransmitter. A variety of evidence suggests that the release
of glutamate then activates N-methyl-d-aspartate (NMDA) receptors
within the SCN and triggers a signaling cascade that ultimately leads
to phase shifts in the circadian system. In this study, we first
sought to explore the role of the NR2B subunit in mediating the effects
of light on the circadian system of hamsters and mice. We found that
localized microinjection of the NR2B subunit antagonist ifenprodil
into the SCN region reduces the magnitude of light-induced phase
shifts of the circadian rhythm in wheel-running activity. Next, we
found that the NR2B message and levels of phospho-NR2B vary with
time of day in SCN tissue using semiquantitative real-time polymerase
chain reaction and western blot analysis, respectively. Functionally,
we found that blocking the NR2B subunit with ifenprodil significantly
reduced the magnitude of NMDA currents recorded in SCN neurons. Ifenprodil
also significantly reduced the magnitude of NMDA-induced Ca2+ changes
in SCN cells. Together, these results demonstrate that the NR2B subunit
is an important component of NMDA receptor-mediated responses within
SCN neurons and that this subunit contributes to light-induced phase
shifts of the mammalian circadian system.},
issn = {1460-9568},
keywords = {Ca2+, circadian rhythms, fura2, ifenprodil, mice, suprachiasmatic
nucleus, Syrian hamsters},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2008.06144.x}
}
@ARTICLE{Wang2011f,
author = {Wang, Min and Hu, Youji and Amatangelo, Michael D. and Stearns, Mark
E.},
title = {Role of Ribosomal Protein RPS2 in Controlling let-7a Expression in
Human Prostate Cancer},
journal = {Mol. Cancer Res.},
year = {2011},
volume = {9},
pages = {36--50},
number = {1},
month = jan,
abstract = {We discovered that an inverse relationship exists in the expression
of ras/c-myc and ribosomal protein RPS2 with pre-let-7a-1/let-7a/let-7f
miRNA and prostate tumor cell malignancy. Nonmalignant IBC-10a cells
expressed low levels of ras/RPS2 and elevated pre-let-7a-1/let-7a/let-7f
miRNA, whereas the reverse occurred in malignant PCa-20a and PC-3ML
cells. Stable transfection of IBC-10a cells with pBABE.ras and pBABE.RPS2
induced ras, c-myc, and RPS2 expression, whereas the levels of let-7a/let-7f
miRNA dropped to near zero. Conversely, in pBABE.pre-let-7a-1 transfected
PCa-20a and PC-3ML clones, let-7a/let-7f increased whereas ras, RPS2,
and c-myc dropped greater than 5-fold. Electrophoretic mobility shift
assays, antibody "supershift" assays and immunoprecipitation assays
revealed that RPS2 specifically binds pre-let-7a-1 to block RNA processing.
Immunoflourescent studies and Northern blots confirmed that RPS2
complexes with pre-let-7a-1 (i.e., in episomal structures) to block
processing to let-7a/let-7f, indicating RPS2 may prevent let-7a miRNA
expression to indirectly promote oncogene expression. Functional
studies further showed that the colony-forming ability (CFA) and
invasive activities of IBC-10a cells were significantly enhanced
in pBABE-ras.IBC-10a and pBABE-RPS2-IBC-10a clones. Conversely, with
the "knockdown" of ras and RPS2 in malignant PC-3ML cells (i.e.,
in pLKO.TRC.shRNA.ras.PC3-ML, pLKO.TRC.shRNA.RPS2.PC-3ML transfected
cells), there was both a loss of these functions and a loss of tumorigenesis
in SCID mice. Likewise, with the overexpression of let-7a/let-7f
in pBABE.pre-let-7a-1.PC-3ML clones (and PCa-20a clones), CFAs, invasive
activities in vitro, and tumorigenesis in vivo were significantly
reduced. These results show for the first time that RPS2 blocks pre-let-7a-1
processing to enable ras and c-myc expression and the transformation
of primary tumor cells. Mol Cancer Res; 9(1); 36-50 (C)2011 AACR.},
comment = {10.1158/1541-7786.MCR-10-0158},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/9/1/36}
}
@ARTICLE{Wang2009k,
author = {Wang, Min and Senger, Ryan S. and Paredes, Carlos and Banik, Gautam
G. and Lin, Andy and Papoutsakis, Eleftherios T.},
title = {Microarray-based gene expression analysis as a process characterization
tool to establish comparability of complex biological products: Scale-up
of a whole-cell immunotherapy product},
journal = {Biotechnol. Bioeng.},
year = {2009},
volume = {104},
pages = {796--808},
number = {4},
abstract = {Abstract 10.1002/bit.22441.abs Whole-cell immunotherapies and other
cellular therapies have shown promising results in clinical trials.
Due to the complex nature of the whole cell product and of the sometimes
limited correlation of clinical potency with the proposed mechanism
of action, these cellular immunotherapy products are generally not
considered well characterized. Therefore, one major challenge in
the product development of whole cell therapies is the ability to
demonstrate comparability of product after changes in the manufacturing
process. Such changes are nearly inevitable with increase in manufacturing
experience leading to improved and robust processes that may have
higher commercial feasibility. In order to comprehensively assess
the impact of the process changes on the final product, and thus
establish comparability, a matrix of characterization assays (in
addition to lot release assays) assessing the various aspects of
the cellular product are required. In this study, we assessed the
capability of DNA-microarray-based, gene-expression analysis as a
characterization tool using GVAX cancer immunotherapy cells manufactured
by Cell Genesys, Inc. The GVAX immunotherapy product consists two
prostate cancer cell lines (CG1940 and CG8711) engineered to secrete
human GM-CSF. To demonstrate the capability of the assay, we assessed
the transcriptional changes in the product when produced in the presence
or absence of fetal bovine serum, and under normal and hypoxic conditions,
both changes intended to stress the cell lines. We then assessed
the impact of an approximately 10-fold process scale-up on the final
product at the transcriptional level. These data were used to develop
comparisons and statistical analyses suitable for characterizing
culture reproducibility and cellular product similarity. Use of gene-expression
data for process characterization proved to be a reproducible and
sensitive method for detecting differences due to small or large
changes in culture conditions as might be encountered in process
scale-up or unanticipated bioprocess failures. Gene expression analysis
demonstrated that cell products of representative lots under the
same production process and at the same production scale were statistically
identical. Large process changes that resulted from the artificial
stress conditions used (absence of FBS and induction of hypoxia)
displayed profoundly different gene expression patterns. We propose
the use of simple t-test analysis in combination with the herein
introduced expression ratio with mean intensity (ERMI) analysis as
useful tools for process characterization by global gene expression
analysis. Biotechnol. Bioeng. 2009; 104: 796–808 © 2009 Wiley
Periodicals, Inc.},
issn = {1097-0290},
keywords = {cellular vaccine, cancer immunotherapy, process characterization,
microarrays, cell culture, genome scale analysis, scale up, quality
control, statistical analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22441}
}
@ARTICLE{Wang2008e,
author = {Wang, Min and Windgassen, Dirk and Papoutsakis, Eleftherios},
title = {Comparative analysis of transcriptional profiling of CD3+, CD4+ and
CD8+ T cells identifies novel immune response players in T-Cell activation},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {225},
number = {1},
abstract = {BACKGROUND:T-cell activation is an essential step of the immune response
and relies on the tightly controlled orchestration of hundreds of
genes/proteins, yet the cellular and molecular events underlying
this complex process are not fully understood, especially at the
genome-scale. Significantly, a comparative genome-scale transcriptional
analysis of two T-cell subsets (CD4+ and CD8+) against each other
and against the naturally mixed population (CD3+ cells) remains unexplored.RESULTS:Comparison
of the microarray-based gene expression patterns between CD3+ T cells,
and the CD4+ and CD8+ subsets revealed largely conserved, but not
identical, transcriptional patterns. We employed a Gene-Ontology-driven
transcriptional analysis coupled with protein abundance assays in
order to identify novel T-cell activation genes and cell-type-specific
genes associated with the immune response. We identified potential
genes involved in the communication between the two subsets (including
IL23A, NR4A2, CD83, PSMB2, -8, MIF, IFI16, TNFAIP1, POU2AF1, and
OTUB1) and would-be effector-function-specific genes (XCL2, SLAMF7,
TNFSF4, -5, -9, CSF3, CD48 and CD244). Chemokines induced during
T-cell activation, but not previously identified in T cells, include
CCL20, CXCL9, -10, -11 (in all three populations), and XCL2 (preferentially
in CD8+ T cells). Increased expression of other unexpected cytokines
(GPI, OSM and MIF) suggests their involvement in T-cell activation
with their functions yet to be examined. Differential expression
of many receptors, not previously reported in the context of T-cell
activation, including CCR5, CCR7, IL1R2, IL1RAP, IL6R, TNFRSF25 and
TNFRSF1A, suggests their role in this immune process. Several receptors
involved in TCR activation (CD3D, CD3G, TRAT1, ITGAL, ITGB1, ITGB2,
CD8A and B (CD8+ T-cell specific) along with LCK, ZAP70 and TYROBP
were synchronously downregulated. Members of cell-surface receptors
(HLA-Ds and KLRs), none previously identified in the context of T-cell
activation, were also downregulated.CONCLUSION:This comparative genome-scale,
transcriptional analysis of T-cell activation in the CD4+ and CD8+
subsets and the mixed CD3+ populations made possible the identification
of many immune-response genes not previously identified in the context
of T-cell activation. Significantly, it made possible to identify
the temporal patterns of many previously known T-cell activation
genes, and also identify genes implicated in effector functions of
and communication between CD4+ and CD8+ T cells.},
doi = {10.1186/1471-2164-9-225},
issn = {1471-2164},
pubmedid = {18485203},
url = {http://www.biomedcentral.com/1471-2164/9/225}
}
@ARTICLE{Wang2012b,
author = {Wang, Ning and Robaye, Bernard and Agrawal, Ankita and Skerry, Timothy
M. and Boeynaems, Jean-Marie and Gartland, Alison},
title = {Reduced Bone Turnover in Mice Lacking the P2Y13 Receptor of ADP},
journal = {Mol. Endocrinol.},
year = {2012},
volume = {26},
pages = {142-152},
number = {1},
abstract = {Osteoporosis is a condition of excessive and uncoupled bone turnover,
in which osteoclastic resorption exceeds osteoblastic bone formation,
resulting in an overall net bone loss, bone fragility, and morbidity.
Although numerous treatments have been developed to inhibit bone
loss by blocking osteoclastic bone resorption, understanding of the
mechanisms behind bone loss is incomplete. The purinergic signaling
system is emerging to be a pivotal regulator of bone homeostasis,
and extracellular ADP has previously been shown to be a powerful
osteolytic agent in vitro. We report here that deletion of the P2Y13
receptor, a G protein-coupled receptor for extracellular ADP, leads
to a 40% reduction in trabecular bone mass, 50% reduction in osteoblast
and osteoclast numbers in vivo, as well as activity in vitro, and
an overall 50% reduction in the rate of bone remodeling in mice in
vivo. Down-regulation of RhoA/ROCK I signaling and a reduced ratio
of receptor activator of nuclear factor {kappa}B ligand/osteoprotegerin
observed in osteoblasts from P2Y13R-/- mice might explain this bone
phenotype. Furthermore, because one of the main causes of osteoporosis
in older women is lack of estrogen, we examined the effect of ovariectomy
of the P2Y13R-/- mice and found them to be protected from ovariectomy-induced
bone loss by up to 65%. These data confirm a role of purinergic ADP
signaling in the skeleton, whereby deletion of the P2Y13 receptor
leads to reduced bone turnover rates, which provide a protective
advantage in conditions of accelerated bone turnover such as oestrogen
deficiency-induced osteoporosis.},
doi = {10.1210/me.2011-1083},
eprint = {http://mend.endojournals.org/cgi/reprint/26/1/142.pdf},
url = {http://mend.endojournals.org/cgi/content/abstract/26/1/142}
}
@ARTICLE{Wang2011i,
author = {Wang, Nicholas J. and Sanborn, Zachary and Arnett, Kelly L. and Bayston,
Laura J. and Liao, Wilson and Proby, Charlotte M. and Leigh, Irene
M. and Collisson, Eric A. and Gordon, Patricia B. and Jakkula, Lakshmi
and Pennypacker, Sally and Zou, Yong and Sharma, Mimansa and North,
Jeffrey P. and Vemula, Swapna S. and Mauro, Theodora M. and Neuhaus,
Isaac M. and LeBoit, Philip E. and Hur, Joe S. and Park, Kyunghee
and Huh, Nam and Kwok, Pui-Yan and Arron, Sarah T. and Massion, Pierre
P. and Bale, Allen E. and Haussler, David and Cleaver, James E. and
Gray, Joe W. and Spellman, Paul T. and South, Andrew P. and Aster,
Jon C. and Blacklow, Stephen C. and Cho, Raymond J.},
title = {Loss-of-function mutations in Notch receptors in cutaneous and lung
squamous cell carcinoma},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {17761-17766},
number = {43},
abstract = {Squamous cell carcinomas (SCCs) are one of the most frequent forms
of human malignancy, but, other than TP53 mutations, few causative
somatic aberrations have been identified. We identified NOTCH1 or
NOTCH2 mutations in [~]75% of cutaneous SCCs and in a lesser fraction
of lung SCCs, defining a spectrum for the most prevalent tumor suppressor
specific to these epithelial malignancies. Notch receptors normally
transduce signals in response to ligands on neighboring cells, regulating
metazoan lineage selection and developmental patterning. Our findings
therefore illustrate a central role for disruption of microenvironmental
communication in cancer progression. NOTCH aberrations include frameshift
and nonsense mutations leading to receptor truncations as well as
point substitutions in key functional domains that abrogate signaling
in cell-based assays. Oncogenic gain-of-function mutations in NOTCH1
commonly occur in human T-cell lymphoblastic leukemia/lymphoma and
B-cell chronic lymphocytic leukemia. The bifunctional role of Notch
in human cancer thus emphasizes the context dependency of signaling
outcomes and suggests that targeted inhibition of the Notch pathway
may induce squamous epithelial malignancies.},
doi = {10.1073/pnas.1114669108},
eprint = {http://www.pnas.org/cgi/reprint/108/43/17761.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/43/17761}
}
@ARTICLE{Wang2010p,
author = {Wang, Peng and Kuhn, Andreas and Dalbey, Ross E.},
title = {Global Change of Gene Expression and Cell Physiology in YidC-Depleted
Escherichia coli},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {2193--2209},
number = {8},
month = apr,
abstract = {YidC depletion affects membrane protein insertion and leads to a defect
in the growth of the Escherichia coli cell. We analyzed global changes
in gene expression upon YidC depletion to determine the importance
of YidC for cellular functions using a gene chip method to compare
the transcriptomes of JS71 (control) and JS7131 (yidC depletion strain).
Of the more than 4,300 genes identified, 163 were upregulated and
99 were downregulated upon YidC depletion, including genes which
are responsible for DNA/RNA repair; energy metabolism; various transporters,
proteases and chaperones; stress response; and translation and transcription
functions. Real-time PCR was performed on selected genes to confirm
the results. Specifically, we found upregulation of the genes encoding
the energy transduction proteins F1Fo ATP synthase and cytochrome
bo3 oxidase due to perturbation in assembly when YidC was depleted.
We also determined that the high-level induction of the PspA stress
protein under YidC depletion conditions is roughly 10-fold higher
than the activation due to the addition of protonophore carbonyl
cyanide m-chlorophenylhydrazone (CCCP), which dissipates the proton
motive force. In addition, the gene chip data reveal the Cpx stress
pathway is activated upon YidC depletion. The data show the broad
physiological contribution of YidC to the bacterial cell and the
considerable ramification to the cell when it is depleted.},
url = {http://jb.asm.org/cgi/content/abstract/192/8/2193}
}
@ARTICLE{Wang2006b,
author = {Wang, Qun and Diskin, Sharon and Rappaport, Eric and Attiyeh, Edward
and Mosse, Yael and Shue, Daniel and Seiser, Eric and Jagannathan,
Jayanti and Shusterman, Suzanne and Bansal, Manisha and Khazi, Deepa
and Winter, Cynthia and Okawa, Erin and Grant, Gregory and Cnaan,
Avital and Zhao, Huaqing and Cheung, Nai-Kong and Gerald, William
and London, Wendy and Matthay, Katherine K. and Brodeur, Garrett
M. and Maris, John M.},
title = {Integrative Genomics Identifies Distinct Molecular Classes of Neuroblastoma
and Shows That Multiple Genes Are Targeted by Regional Alterations
in DNA Copy Number},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {6050--6062},
number = {12},
month = jun,
abstract = {Neuroblastoma is remarkable for its clinical heterogeneity and is
characterized by genomic alterations that are strongly correlated
with tumor behavior. The specific genes that influence neuroblastoma
biology and are targeted by genomic alterations remain largely unknown.
We quantified mRNA expression in a highly annotated series of 101
prospectively collected diagnostic neuroblastoma primary tumors using
an oligonucleotide-based microarray. Genomic copy number status at
the prognostically relevant loci 1p36, 2p24 (MYCN), 11q23, and 17q23
was determined by PCR and was aberrant in 26, 20, 40, and 38 cases,
respectively. In addition, 72 diagnostic neuroblastoma primary tumors
assayed in a different laboratory were used as an independent validation
set. Unsupervised hierarchical clustering showed that gene expression
was highly correlated with genomic alterations and clinical markers
of tumor behavior. The vast majority of samples with MYCN amplification
and 1p36 loss of heterozygosity (LOH) clustered together on a terminal
node of the sample dendrogram, whereas the majority of samples with
11q deletion clustered separately and both of these were largely
distinct from the copy number neutral group of tumors. Genes involved
in neurodevelopment were broadly overrepresented in the more benign
tumors, whereas genes involved in RNA processing and cellular proliferation
were highly represented in the most malignant cases. By combining
transcriptomic and genomic data, we showed that LOH at 1p and 11q
was associated with significantly decreased expression of 122 (61%)
and 88 (27%) of the genes mapping to 1p35-36 and all of 11q, respectively,
suggesting that multiple genes may be targeted by LOH events. A total
of 71 of the 1p35-36 genes were also differentially expressed in
the independent validation data set, providing a prioritized list
of candidate neuroblastoma suppressor genes. Taken together, these
data are consistent with the hypotheses that the neuroblastoma transcriptome
is a sensitive marker of underlying tumor biology and that chromosomal
deletion events in this cancer likely target multiple genes through
alteration in mRNA dosage. Lead positional candidates for neuroblastoma
suppressor genes can be inferred from these data, but the potential
multiplicity of transcripts involved has significant implications
for ongoing gene discovery strategies. (Cancer Res 2006; 66(12):
6050-62)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/12/6050}
}
@ARTICLE{Wang2010n,
author = {Wang, Qin and Rajshankar, Dhaarmini and Laschinger, Carol and Talior-Volodarsky,
Ilana and Wang, Yongqiang and Downey, Gregory P. and McCulloch, Christopher
A.},
title = {Importance of Protein-tyrosine Phosphatase-{alpha} Catalytic Domains
for Interactions with SHP-2 and Interleukin-1-induced Matrix Metalloproteinase-3
Expression},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {22308--22317},
number = {29},
month = jul,
abstract = {Interleukin-1 (IL-1) induces extracellular matrix degradation as a
result of increased expression of matrix metalloproteinases (MMPs).
We examined adhesion-restricted signaling pathways that enable IL-1-induced
MMP release in human gingival and murine fibroblasts. Of the seven
MMPs and three tissue inhibitors of MMPs screened, IL-1 enhanced
release only of MMP3 when cells formed focal adhesions. Inhibition
of protein-tyrosine phosphatases (PTPs), which are enriched in focal
adhesions, blocked IL-1-induced MMP3 release. Accordingly, in contrast
to wild-type cells, fibroblasts null for PTP{alpha} did not exhibit
IL-1-induced MMP3 release. IL-1 treatment enhanced the recruitment
of SHP-2 and PTP{alpha} to focal adhesions and the association of
PTP{alpha} with SHP-2. Pulldown assays confirmed a direct interaction
between PTP{alpha} and SHP-2, which was dependent on the intact,
membrane-proximal phosphatase domain of PTP{alpha}. Interactions
between SHP-2 and PTP{alpha}, recruitment of SHP-2 to focal adhesions,
IL-1-induced ERK activation, and MMP3 expression were all blocked
by point mutations in the phosphatase domains of PTP{alpha}. These
data indicate that IL-1-induced signaling through focal adhesions
leading to MMP3 release and interactions between SHP-2 and PTP{alpha}
are dependent on the integrity of the catalytic domains of PTP{alpha}.},
url = {http://www.jbc.org/cgi/content/abstract/285/29/22308}
}
@ARTICLE{Wang2010b,
author = {Wang, Qin Qin and Liu, Fei and Chen, Xu Sheng and Ma, Xiao Jie and
Zeng, Hou Qing and Yang, Zhi Min},
title = {Transcriptome profiling of early developing cotton fiber by deep-sequencing
reveals significantly differential expression of genes in a fuzzless/lintless
mutant},
journal = {Genomics},
year = {2010},
volume = {96},
pages = {369--376},
number = {6},
month = dec,
abstract = {Cotton fiber as a single-celled trichome is a biological model system
for studying cell differentiation and elongation. However, the complexity
of its gene expression and regulatory mechanism allows only marginal
progress. Here, we report the high-throughput tag-sequencing (Tag-seq)
analysis using Solexa Genome Analyzer platform on transcriptome of
-2 to 1 (fiber initiation, stage I) and 2-8 (fiber elongation, stage
II) days post anthesis (DPA) cotton (Gossypium hirsutum) ovules (wild
type: WT; Xuzhou 142 and its mutant: fuzzless/lintless or fl M, in
the same background). To this end, we sequenced 3.5-3.8 million tags
representing 0.7-1.0 million unique transcripts for each library
(WT1, WT2, M1, and M2). After removal of low quality tags, we obtained
a total of 2,973,104, 3,139,306, 2,943,654, and 3,392,103 clean sequences
that corresponded to 357,852, 280,787, 372,952, and 382,503 distinct
tags for WT1, WT2, M1, and M2, respectively. All clean tags were
aligned to the publicly available cotton transcript database (TIGR,
http://www.tigr.org). About 15% of the distinct tags were uniquely
mapped to the reference genes, and 31.4% of existing genes were matched
by tags. The tag mapping to the database sequences generated 23,854,
24,442, 23,497, and 19,957 annotated genes for WT1, WT2, M1, and
M2 libraries, respectively. Analyses of differentially expressed
genes revealed the substantial changes in gene type and abundance
between the wild type and mutant libraries. Among the 20 most differentially
expressed genes in WT1/M1 and WT2/M2 libraries were cellulose synthase,
phosphatase, and dehydrogenase, all of which are involved in the
fiber cell development. Overall, the deep-sequencing analyses demonstrate
the high degree of transcriptional complexity in early developing
fibers and represent a major improvement over the microarrays for
analyzing transcriptional changes on a large scale.},
issn = {0888-7543},
keywords = {Gossypium hirsutum, Fiber, Transcriptome, Deep-sequencing, MicroRNA
target gene},
url = {http://www.sciencedirect.com/science/article/pii/S0888754310001953}
}
@ARTICLE{Wang2005e,
author = {Wang, Rui and Boules, Mona and Gollatz, Elisa and Williams, Katrina
and Tiner, William and Richelson, Elliott},
title = {Effects of 5 daily injections of the neurotensin-mimetic NT69L on
the expression of neurotensin receptors in rat brain},
journal = {Molecular Brain Research},
year = {2005},
volume = {138},
pages = {24--34},
number = {1},
month = jul,
abstract = {The effects of one or five daily intraperitoneal injections of a neurotensin
(NT) receptor agonist NT69L (2 mg/kg, i.p.) on the expression of
NT (NTS), dopamine 1 and 2 receptors, tyrosine hydroxylase, and DOPA
decarboxylase using immunohistochemical and real-time PCR were investigated
in rats. Except for the striatum, acute injection of NT69L did not
affect neurotensin receptors as compared to saline control. However,
5 daily injections of NT69L resulted in down-regulation of both NTS-1
protein and mRNA levels in several brain regions with the striatum
showing a dramatic decrease in NTS-1 expression (P < 0.05). The down-regulation
of NTS-1 in the striatum, hypothalamus, and substania nigra (SN)
after 5 daily injections was confirmed by autoradiography. Acute
injection of NT69L increased NTS-2 mRNA and protein level in prefrontal
cortex (PFC). NTS-3 mRNA expression and protein levels were slightly
down-regulated in hypothalamus, periaqueductal gray (PAG), and SN,
though the difference was not significant. The results indicated
a difference in the profile of NT receptors expression in response
to NT69L. Tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC)
mRNA was significantly down-regulated in striatum but not in SN.
Interestingly, Nurr1, a transcriptional activator of TH, was dramatically
up-regulated in striatum, but down-regulated in PFC, suggesting that
different modulating mechanisms may participate in NT69L tolerance
in different regions. The present results suggest that distinct NT
receptors involved in the effects exerted by NT69L may contribute
to the interactions of NT69L with both neural networks and cellular
proteins.},
issn = {0169-328X},
keywords = {Neurotensin agonist, Tolerance, Neurotensin receptors, mRNA, Tyrosine
hydroxylase, Rat},
url = {http://www.sciencedirect.com/science/article/B6T07-4G3619W-1/2/8892617d667dce9572411c0a85e334e2}
}
@ARTICLE{Wang2003a,
author = {Wang, Rongchen and Okamoto, Mamoru and Xing, Xiujuan and Crawford,
Nigel M.},
title = {Microarray Analysis of the Nitrate Response in Arabidopsis Roots
and Shoots Reveals over 1,000 Rapidly Responding Genes and New Linkages
to Glucose, Trehalose-6-Phosphate, Iron, and Sulfate Metabolism},
journal = {Plant Physiology},
year = {2003},
volume = {132},
pages = {556--567},
number = {2},
month = jun,
abstract = {The genomic response to low levels of nitrate was studied in Arabidopsis
using the Affymetrix ATH1 chip containing more than 22,500 probe
sets. Arabidopsis plants were grown hydroponically in sterile liquid
culture on ammonium as the sole source of nitrogen for 10 d, then
treated with 250 {micro}M nitrate for 20 min. The response to nitrate
was much stronger in roots (1,176 genes showing increased or decreased
mRNA levels) than in shoots (183 responding genes). In addition to
known nitrate-responsive genes (e.g. those encoding nitrate transporters,
nitrate reductase, nitrite reductase, ferredoxin reductase, and enzymes
in the pentose phosphate pathway), genes encoding novel metabolic
and potential regulatory proteins were found. These genes encode
enzymes in glycolysis (glucose-6-phosphate isomerase and phosphoglycerate
mutase), in trehalose-6-P metabolism (trehalose-6-P synthase and
trehalose-6-P phosphatase), in iron transport/metabolism (nicotianamine
synthase), and in sulfate uptake/reduction. In many cases, only a
few select genes out of several in small gene families were induced
by nitrate. These results show that the effect of nitrate on gene
expression is substantial (affecting almost 10% of the genes with
detectable mRNA levels) yet selective and affects many genes involved
in carbon and nutrient metabolism.},
url = {http://www.plantphysiol.org/cgi/content/abstract/132/2/556}
}
@ARTICLE{Wang2010g,
author = {Wang, Rui and Wang, Guoqing and Ricard, Megan J. and Ferris, Barbara
and Strulovici-Barel, Yael and Salit, Jacqueline and Hackett, Neil
R. and Gudas, Lorraine J. and Crystal, Ronald G.},
title = {Smoking-Induced Upregulation of AKR1B10 Expression in the Airway
Epithelium of Healthy Individuals},
journal = {Chest},
year = {2010},
volume = {138},
pages = {1402--1410},
number = {6},
month = dec,
abstract = {BackgroundThe aldo-keto reductase (AKR) gene superfamily codes for
monomeric, soluble reduced nicotinamide adenine dinucleotide phosphate-dependent
oxidoreductases that mediate elimination reactions. AKR1B10, an AKR
that eliminates retinals, has been observed as upregulated in squamous
metaplasia and non-small cell lung cancer and has been suggested
as a diagnostic marker specific to tobacco-related carcinogenesis.
We hypothesized that upregulation of AKR1B10 expression may be initiated
in healthy smokers prior to the development of evidence of lung cancer.
MethodsExpression of AKR1B10 was assessed at the mRNA level using
microarrays with TaqMan confirmation in the large airway epithelium
(21 healthy nonsmokers, 31 healthy smokers) and small airway epithelium
(51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic
bronchoscopy and brushing. ResultsCompared with healthy nonsmokers,
AKR1B10 mRNA levels were significantly upregulated in both large
and small airway epithelia of healthy smokers. Consistent with the
mRNA data, AKR1B10 protein was significantly upregulated in the airway
epithelium of healthy smokers as assessed by Western blot analysis
and immunohistochemistry, with AKR1B10 expressed in both differentiated
and basal cells. Finally, cigarette smoke extract mediated upregulation
of AKR1B10 in airway epithelial cells in vitro, and transfection
of AKR1B10 into airway epithelial cells enhanced the conversion of
retinal to retinol. ConclusionsSmoking per se mediates upregulation
of AKR1B10 expression in the airway epithelia of healthy smokers
with no evidence of lung cancer. In the context of these observations
and the link of AKR1B10 to the metabolism of retinals and to lung
cancer, the smoking-induced upregulation of AKR1B10 may be an early
process in the multiple events leading to lung cancer.},
comment = {10.1378/chest.09-2634},
url = {http://chestjournal.chestpubs.org/cgi/content/abstract/138/6/1402}
}
@ARTICLE{Wang2008f,
author = {Wang, Rong-Lin and Biales, Adam and Bencic, David and Lattier, David
and Kostich, Mitch and Villeneuve, Dan and Ankley, Gerald T. and
Lazorchak, Jim and Toth, Greg},
title = {DNA microarray application in ecotoxicology: Experimental design,
microarray scanning, and factors affecting transcriptional profiles
in a small fish species},
journal = {Environmental Toxicology and Chemistry},
year = {2008},
volume = {27},
pages = {652--663},
number = {3},
abstract = {Abstract 10.1897/07-191.1.abs The research presented here is part
of a larger study of the molecular mode of action of endocrine-disrupting
chemicals targeting the hypothalamic–pituitary–gonadal axis in
zebrafish (Danio rerio). It addresses several issues critical to
microarray application in aquatic ecotoxicology: experimental design,
microarray scanning, gene expression intensity distribution, and
the effect of experimental parameters on the zebrafish transcriptome.
Expression profiles from various tissues of individual zebrafish
exposed to 17α-ethinylestradiol (30 ng/L), fadrozole (25 μg/L),
or 17β-trenbolone (3.0 μg/L) for 48 or 96 h were examined with
the Agilent Oligo Microarray (G2518A). As a flexible and efficient
alternative to the designs commonly used in microarray studies, an
unbalanced incomplete block design was found to be well suited for
this work, as evidenced by high data reproducibility, low microarray-to-microarray
variability, and little gene-specific dye bias. Random scanner noise
had little effect on data reproducibility. A low-level, slightly
variable Cyanine 3 (Cy3) contaminant was revealed by hyperspectral
imaging, suggesting fluorescence contamination as a potential contributor
to the large variance associated with weakly expressed genes. Expression
intensities of zebrafish genes were skewed toward the lower end of
their distribution range, and more weakly expressed genes tended
to have larger variances. Tissue type, followed in descending order
by gender, chemical treatment, and exposure duration, had the greatest
effect on the overall gene expression profiles, a finding potentially
critical to experimental design optimization. Overall, congruence
was excellent between quantitative polymerase chain reaction results
and microarray profiles of 13 genes examined across a subset of 20
pairs of ovarian samples. These findings will help to improve applications
of microarrays in future ecotoxicological studies.},
issn = {1552-8618},
keywords = {Microarray, Design, Scan, Zebrafish, Ecotoxicology},
publisher = {Wiley Periodicals, Inc.},
url = {http://dx.doi.org/10.1897/07-191.1}
}
@ARTICLE{Wang2009l,
author = {Wang, Siyun and Deng, Kaiping and Zaremba, Sam and Deng, Xiangyu
and Lin, Chiahui and Wang, Qian and Tortorello, Mary Lou and Zhang,
Wei},
title = {Transcriptomic Response of Escherichia coli O157:H7 to Oxidative
Stress},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {6110--6123},
number = {19},
month = oct,
abstract = {Chlorinated water is commonly used in industrial operations to wash
and sanitize fresh-cut, minimally processed produce. Here we compared
42 human outbreak strains that represented nine distinct Escherichia
coli O157:H7 genetic lineages (or clades) for their relative resistance
to chlorine treatment. A quantitative measurement of resistance was
made by comparing the extension of the lag phase during growth of
each strain under exposure to sublethal concentrations of sodium
hypochlorite in Luria-Bertani or brain heart infusion broth. Strains
in clade 8 showed significantly (P < 0.05) higher resistance to chlorine
than strains from other clades of E. coli O157:H7. To further explore
how E. coli O157:H7 responds to oxidative stress at transcriptional
levels, we analyzed the global gene expression profiles of two strains,
TW14359 (clade 8; associated with the 2006 spinach outbreak) and
Sakai (clade 1; associated with the 1996 radish sprout outbreak),
under sodium hypochlorite or hydrogen peroxide treatment. We found
over 380 genes were differentially expressed (more than twofold;
P < 0.05) after exposure to low levels of chlorine or hydrogen peroxide.
Significantly upregulated genes included several regulatory genes
responsive to oxidative stress, genes encoding putative oxidoreductases,
and genes associated with cysteine biosynthesis, iron-sulfur cluster
assembly, and antibiotic resistance. Identification of E. coli O157:H7
strains with enhanced resistance to chlorine decontamination and
analysis of their transcriptomic response to oxidative stress may
improve our basic understanding of the survival strategy of this
human enteric pathogen on fresh produce during minimal processing.},
url = {http://aem.asm.org/cgi/content/abstract/75/19/6110}
}
@ARTICLE{Wang2011h,
author = {Shaoyun Wang and Amrita Kamat and Pablo Pergola and Anita Swamy and
Fermin Tio and Kenneth Cusi},
title = {Metabolic factors in the development of hepatic steatosis and altered
mitochondrial gene expression in vivo},
journal = {Metabolism},
year = {2011},
volume = {60},
pages = {1090 - 1099},
number = {8},
abstract = {The objective of the study was to understand the role in vivo of elevated
plasma free fatty acids (FFA), insulin, and glucose levels in the
development of steatosis and altered mitochondrial gene/protein expression.
We studied 4 groups of Sprague-Dawley rats: (1) high-fat diet (HFD),
(2) high-dose streptozotocin–induced diabetes (T1DM), (3) low-dose
streptozotocin–induced diabetic rats on an HFD (T2DM), and (4)
controls. Liver histology and expression of genes/proteins related
to mitochondrial fatty acid oxidation and biogenesis were analyzed.
Despite an attempt to compensate by increasing expression of genes
of fatty acid oxidation (carnitine palmitoyl transferase–1/medium
chain acyl-CoA dehydrogenase), the HFD and diabetic groups developed
marked steatosis and suffered a significant reduction in mitochondrial
biogenesis gene expression (nuclear respiratory factor 1/transcriptional
factor A, mitochondrial). In T2DM rats, the combination of high glucose
and FFA unexpectedly did not lead to greater fat accumulation than
HFD alone. Greater steatosis in HFD vs T2DM (P < .001) correlated
with impairment in the gene expression of PPAR-α (ie, fatty acid
oxidation) and PGC1α, a major coactivator for mitochondrial biogenesis.
Steatosis was not severe in insulin-deficient T1DM rats despite very
elevated FFA and glucose levels. Increased carnitine palmitoyl transferase–1/medium
chain acyl-CoA dehydrogenase/PPAR-α gene expression suggested inadequate
adaptation to high FFA in both T1DM/T2DM rats. Hyperinsulinemia combined
with elevated FFA is the key metabolic factor driving hepatic lipogenesis
in vivo (HFD rats). Mitochondrial biogenesis (nuclear respiratory
factor 1; transcriptional factor A, mitochondrial) is highly susceptible
to FFA-induced steatosis. In contrast, hyperglycemia does not have
an additive effect (T2DM) and leads to only a modest degree of steatosis
in the absence of hyperinsulinemia, even when FFA are extremely elevated
as in T1DM rats.},
doi = {10.1016/j.metabol.2010.12.001},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/pii/S0026049510003872}
}
@ARTICLE{Wang2010l,
author = {Wang, Shaolin and Peatman, Eric and Liu, Hong and Bushek, David and
Ford, Susan E. and Kucuktas, Huseyin and Quilang, Jonas and Li, Ping
and Wallace, Richard and Wang, Yongping and Guo, Ximing and Liu,
Zhanjiang},
title = {Microarray analysis of gene expression in eastern oyster (Crassostrea
virginica) reveals a novel combination of antimicrobial and oxidative
stress host responses after dermo (Perkinsus marinus) challenge},
journal = {Fish \& Shellfish Immunology},
year = {2010},
volume = {29},
pages = {921--929},
number = {6},
month = dec,
abstract = {Dermo disease, caused by Perkinsus marinus, is one of the most severe
diseases of eastern oysters, Crassostrea virginica. It causes serious
mortalities in both wild and aquacultured oysters. Using existing
expressed sequence tag (EST) resources, we developed a 12K in situ
oligonucleotide microarray and used it for the analysis of gene expression
profiles of oysters during the interactions between P. marinus and
its oyster host. Significant gene expression regulation was found
at day 30 post-challenge in the eastern oyster. Putative identities
of the differentially expressed genes revealed a set of genes involved
in several processes including putative antimicrobial defenses, pathogen
recognition and uptake, anti-oxidation and apoptosis. Consistent
with results obtained from previous, smaller-scale experiments, expression
profiles revealed a large set of genes likely involved in an active
mitigating response to oxidative stress and apoptosis induced by
P. marinus. Additionally, a unique galectin from C. virginica, CvGal,
which serves as a preferential receptor for P. marinus trophozoites,
was found to be significantly down-regulated in gill tissue of oysters
with both light and heavy infection, suggesting an attempt to control
parasite uptake and proliferation in the later stages of infection.
Potential histone-derived antimicrobial responses to P. marinus were
also revealed in the gene expression profiles.},
issn = {1050-4648},
keywords = {Oyster, Microarray, Dermo, Oxidative stress, Antimicrobial},
url = {http://www.sciencedirect.com/science/article/B6WFN-50S2R9T-1/2/2d1e83b420b1cb9af686012b7fbe82db}
}
@ARTICLE{Wang2010,
author = {Wang, Siyun and Phillippy, Adam M. and Deng, Kaiping and Rui, Xiaoqian
and Li, Zengxin and Tortorello, Mary Lou and Zhang, Wei},
title = {Transcriptomic Responses of Salmonella enterica Serovars Enteritidis
and Typhimurium to Chlorine-Based Oxidative Stress},
journal = {Appl. Envir. Microbiol.},
year = {2010},
volume = {76},
pages = {5013--5024},
number = {15},
month = aug,
abstract = {Salmonella enterica serovars Enteritidis and Typhimurium are the leading
causative agents of salmonellosis in the United States. S. Enteritidis
is predominantly associated with contamination of shell eggs and
egg products, whereas S. Typhimurium is frequently linked to tainted
poultry meats, fresh produce, and recently, peanut-based products.
Chlorine is an oxidative disinfectant commonly used in the food industry
to sanitize the surfaces of foods and food processing facilities
(e.g., shell eggs and poultry meats). However, chlorine disinfection
is not always effective, as some S. enterica strains may resist and
survive the disinfection process. To date, little is known about
the underlying mechanisms of how S. enterica responds to chlorine-based
oxidative stress. In this study, we designed a custom bigenome microarray
that consists of 385,000 60-mer oligonucleotide probes and targets
4,793 unique gene features in the genomes of S. Enteritidis strain
PT4 and S. Typhimurium strain LT2. We explored the transcriptomic
responses of both strains to two different chlorine treatments (130
ppm of chlorine for 30 min and 390 ppm of chlorine for 10 min) in
brain heart infusion broth. We identified 209 S. enterica core genes
associated with Fe-S cluster assembly, cysteine biosynthesis, stress
response, ribosome formation, biofilm formation, and energy metabolism
that were differentially expressed (>1.5-fold; P < 0.05). In addition,
we found that serovars Enteriditis and Typhimurium differed in the
responses of 33 stress-related genes and 19 virulence-associated
genes to the chlorine stress. Findings from this study suggest that
the oxidative-stress response may render S. enterica resistant or
susceptible to certain types of environmental stresses, which in
turn promotes the development of more effective hurdle interventions
to reduce the risk of S. enterica contamination in the food supply.},
url = {http://aem.asm.org/cgi/content/abstract/76/15/5013}
}
@ARTICLE{Wang2010m,
author = {Wang, Shuyang and Wang, Lei and Zhu, Tengfang and Gao, Xue and Li,
Jian and Wu, Ying and Zhu, Hongguang},
title = {Improvement of tissue preparation for laser capture microdissection:
application for cell type-specific miRNA expression profiling in
colorectal tumors},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {163},
number = {1},
abstract = {BACKGROUND:Laser capture microdissection (LCM) has successfully isolated
pure cell populations from tissue sections and the combination of
LCM with standard genomic and proteomic methods has revolutionized
molecular analysis of complex tissue. However, the quantity and quality
of material recovered after LCM is often still limited for analysis
by using whole genomic and proteomic approaches. To procure high
quality and quantity of RNA after LCM, we optimized the procedures
on tissue preparations and applied the approach for cell type-specific
miRNA expression profiling in colorectal tumors.RESULTS:We found
that the ethanol fixation of tissue sections for 2 hours had the
maximum improvement of RNA quality (1.8 fold, p=0.0014) and quantity
(1.5 fold, p=0.066). Overall, the quality (RNA integrity number,
RIN) for the microdissected colorectal tissues was 5.2 +/- 1.5 (average
+/- SD) for normal (n=43), 5.7 +/- 1.1 for adenomas (n=14) and 7.2
+/- 1.2 for carcinomas (n=44). We then compared miRNA expression
profiles of 18 colorectal tissues (6 normal, 6 adenomas and 6 carcinomas)
between LCM selected epithelial cells versus stromal cells using
Agilent miRNA microarrays. We identified 51 differentially expressed
miRNAs (p<=0.001) between these two cell types. We found that the
miRNAs in the epithelial cells could differentiate adenomas from
normal and carcinomas. However, the miRNAs in the stromal and mixed
cells could not separate adenomas from normal tissues. Finally, we
applied quantitative RT-PCR to cross-verify the expression patterns
of 7 different miRNAs using 8 LCM-selected epithelial cells and found
the excellent correlation of the fold changes between the two platforms
(R=0.996).CONCLUSIONS:Our study demonstrates the feasibility and
potential power of discovering cell type-specific miRNA biomarkers
in complex tissue using combination of LCM with genome-wide miRNA
analysis. },
doi = {10.1186/1471-2164-11-163},
issn = {1471-2164},
pubmedid = {20219115},
url = {http://www.biomedcentral.com/1471-2164/11/163}
}
@ARTICLE{Wang2010h,
author = {Wang, Sunan and Zhao, Weikang and Raza, Asad and Friendship, Robert
and Johnson, Roger and Kostrzynska, Magdalena and Warriner, Keith},
title = {Prevalence of Salmonella infecting bacteriophages associated with
Ontario pig farms and the holding area of a high capacity pork processing
facility},
journal = {J. Sci. Food Agric.},
year = {2010},
volume = {90},
pages = {2318--2325},
number = {13},
abstract = {Abstract BACKGROUND: There is interest in applying bacteriophages
to control Salmonella in pig production and pork processing. The
following reports on the prevalence of Salmonella infecting bacteriophages
within Ontario pig farms and associated with the holding area of
a pork slaughterhouse. RESULTS:Salmonella infecting bacteriophages
were present in 30 and 28 of the effluent manure samples collected
from 36 farms using S. Typhimurium DT104 or S. Heidelberg as host
cell respectively. Bacteriophages were recovered in 95–100% of
the 48 samples taken from holding pens within a high capacity slaughterhouse
over a 12 month period. Bacteriophages isolated from farms exhibited
similar host ranges which differed to that of slaughterhouse isolates.
Salmonella (n = 21) from the slaughterhouse were susceptible to the
endogenous bacteriophages. Despite being susceptible to the resident
phages, the Salmonella populations were found to be genetically stable
with the same genotypes being recovered over successive visits. Salmonella
isolated from the farms were frequently resistant to the endogenous
phages. CONCLUSIONS: Bacteriophages are prevalent in the pig slaughterhouse
environment although they do not have a significant impact on the
genetic structure of Salmonella populations. However, there was evidence
that the Salmonella population structure on farms is influenced by
the presence of infecting phages. Copyright © 2010 Society of Chemical
Industry},
issn = {1097-0010},
keywords = {Salmonella, bacteriophages, pigs, rep-PCR, biocontrol},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jsfa.4090}
}
@ARTICLE{Wang2011t,
author = {Wang, Sidney H. and Elgin, Sarah C. R.},
title = {Drosophila Piwi functions downstream of piRNA production mediating
a chromatin-based transposon silencing mechanism in female germ line},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {21164-21169},
number = {52},
abstract = {Transposon control is a critical process during reproduction. The
PIWI family proteins can play a key role, using a piRNA-mediated
slicing mechanism to suppress transposon activity posttranscriptionally.
In Drosophila melanogaster, Piwi is predominantly localized in the
nucleus and has been implicated in heterochromatin formation. Here,
we use female germ-line-specific depletion to study Piwi function.
This depletion of Piwi leads to infertility and to axis specification
defects in the developing egg chambers; correspondingly, widespread
loss of transposon silencing is observed. Germ-line Piwi does not
appear to be required for piRNA production. Instead, Piwi requires
Aubergine (and presumably secondary piRNA) for proper localization.
A subset of transposons that show significant overexpression in germ-line
Piwi-depleted ovaries exhibit a corresponding loss of HP1a and H3K9me2.
Germ-line HP1a depletion also leads to a loss of transposon silencing,
demonstrating the functional requirement for HP1a enrichment at these
loci. Considering our results and those of others, we infer that
germ-line Piwi functions downstream of piRNA production to promote
silencing of some transposons via recruitment of HP1a. Thus, in addition
to its better-known function in posttranscriptional silencing, piRNA
also appears to function in a targeting mechanism for heterochromatin
formation mediated by Piwi.},
doi = {10.1073/pnas.1107892109},
eprint = {http://www.pnas.org/cgi/reprint/108/52/21164.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/52/21164}
}
@ARTICLE{Wang2002a,
author = {Wang, Steven W. and Mu, Xiuqian and Bowers, William J. and Klein,
William H.},
title = {Retinal ganglion cell differentiation in cultured mouse retinal explants},
journal = {Methods},
year = {2002},
volume = {28},
pages = {448--456},
number = {4},
month = dec,
issn = {1046-2023},
keywords = {Genetically engineered mice, Mouse retinal explants, Herpes simplex
virus expression vectors, Retinal ganglion cell gene expression},
url = {http://www.sciencedirect.com/science/article/B6WN5-47HPPCJ-B/2/2cc07ba280f93999224d28f4c0876b97}
}
@ARTICLE{Wang2006c,
author = {Wang, San-Lang and Lin, Tzu-Yin and Yen, Yue-Horng and Liao, Hui-Fen
and Chen, Yu-Jen},
title = {Bioconversion of shellfish chitin wastes for the production of Bacillus
subtilis W-118 chitinase},
journal = {Carbohydrate Research},
year = {2006},
volume = {341},
pages = {2507--2515},
number = {15},
month = nov,
abstract = {Bacillus subtilis W-118, a strain that produces antifungal materials,
excreted a chitinase when cultured in a medium containing shrimp-
and crab-shell powder as the major carbon source. This chitinase,
purified by sequential chromatography, had a molecular mass of 20,600 Da
and a pI of 6. The optimum pH, optimum temperature, and pH stability
of the chitinase were pH 6, 37 °C, and pH 5-7, respectively. The
unique characteristics of the purified chitinase include low molecular
mass and acidic pI. In the investigation of the inhibitory activity,
it was found that the growth of Fusarium oxysporum was 100% inhibited
after incubation for 1 day with sterilized W-118 chitinase solution
(5.6 units/mL). The chitinase hydrolyzates of chitin with low degrees
of polymerization (DP 1-6) were analyzed by HPLC. Longer reaction
times led to the generation of chitin oligosaccharides with lower
DP. The chitin oligosaccharides were examined for their inhibitory
effects on F. oxysporum and human leukemia cell lines.},
issn = {0008-6215},
keywords = {Chitinase, Bacillus subtilis, Antifungal, Chitin oligosaccharides,
Antitumor},
url = {http://www.sciencedirect.com/science/article/B6TFF-4KPNB1G-1/2/2c1f4fc407c8aae6523192b03f47c372}
}
@ARTICLE{Wang2011k,
author = {Wang, Tao and Papoutsi, Maria and Wiesmann, Marion and DeCristofaro,
Marc and Keselica, M. Craig and Skuba, Elizabeth and Spaet, Robert
and Markovits, Judit and Wolf, Armin and Moulin, Pierre and Pognan,
Francois and Vancutsem, Paul and Petryk, Lew and Sutton, James and
Chibout, Salah-Dine and Kluwe, William},
title = {Investigation of Correlation Among Safety Biomarkers in Serum, Histopathological
Examination, and Toxicogenomics},
journal = {International Journal of Toxicology},
year = {2011},
volume = {30},
pages = {300-312},
number = {3},
abstract = {This article addresses the issue of miscorrelation between hepatic
injury biomarkers and histopathological findings in the drug development
context. Our studies indicate that the use of toxicogenomics can
aid in the drug development decision-making process associated with
such miscorrelated data. BLZ945 was developed as a Colony-Stimulating
Factor 1 Receptor (CSF-1R) inhibitor. Treatment of BLZ945 in rats
and monkeys increased serum alanine aminotransferase (ALT) and aspartate
transaminase (AST). However, liver hypertrophy was the only histopathological
liver finding in rats, and there was no change in the livers of monkeys.
Longer treatment of BLZ945 in rats for 6 weeks caused up to 6-fold
elevation of ALT, yet hepatocyte necrosis was not detected microscopically.
Toxicogenomic profiling of liver samples demonstrated that the genes
associated with early response to liver injury, apoptosis/necrosis,
inflammation, oxidative stress, and metabolic enzymes were upregulated.
Studies are ongoing to evaluate the mechanisms underlying BL945-induced
ALT and AST elevations.},
doi = {10.1177/1091581811401920},
eprint = {http://ijt.sagepub.com/cgi/reprint/30/3/300.pdf},
url = {http://ijt.sagepub.com/cgi/content/abstract/30/3/300}
}
@ARTICLE{Wang2005f,
author = {Wang, Tian-Tian and Tavera-Mendoza, Luz Elisa and Laperriere, David
and Libby, Eric and Burton MacLeod, Naomi and Nagai, Yoshihiko and
Bourdeau, Veronique and Konstorum, Anna and Lallemant, Benjamin and
Zhang, Rui and Mader, Sylvie and White, John H.},
title = {Large-Scale in Silico and Microarray-Based Identification of Direct
1,25-Dihydroxyvitamin D3 Target Genes},
journal = {Mol. Endocrinol.},
year = {2005},
volume = {19},
pages = {2685--2695},
number = {11},
month = nov,
abstract = {1{alpha},25-Dihydroxyvitamin D3 [1,25(OH)2D3] regulates calcium homeostasis
and controls cellular differentiation and proliferation. The vitamin
D receptor (VDR) is a ligand-regulated transcription factor that
recognizes cognate vitamin D response elements (VDREs) formed by
direct or everted repeats of PuG(G/T)TCA motifs separated by 3 or
6 bp (DR3 or ER6). Here, we have identified direct 1,25(OH)2D3 target
genes by combining 35,000+ gene microarrays and genome-wide screens
for consensus DR3 and ER6 elements, and DR3 elements containing single
nucleotide substitutions. We find that the effect of a nucleotide
substitution on VDR binding in vitro does not predict VDRE function
in vivo, because substitutions that disrupted binding in vitro were
found in several functional elements. Hu133A microarray analyses,
performed with RNA from human SCC25 cells treated with 1,25(OH)2D3
and protein synthesis inhibitor cycloheximide, identified more than
900 regulated genes. VDREs lying within -10 to +5 kb of 5'-ends were
assigned to 65% of these genes, and VDR binding was confirmed to
several elements in vivo. A screen of the mouse genome identified
more than 3000 conserved VDREs, and 158 human genes containing conserved
elements were 1,25(OH2)D3-regulated on Hu133A microarrays. These
experiments also revealed 16 VDREs in 11 of 12 genes induced more
than 10-fold in our previous microarray study, five elements in the
human gene encoding the epithelial calcium channel TRPV6, as well
as novel 1,25(OH2)D3 target genes implicated in regulation of cell
cycle progression. The combined approaches used here thus provide
numerous insights into the direct target genes underlying the broad
physiological actions of 1,25(OH)2D3.},
url = {http://mend.endojournals.org/cgi/content/abstract/19/11/2685}
}
@ARTICLE{Wang2005g,
author = {Wang, Wenhua and Andersson, Marianne and Lõnnroth, Christina and
Svanberg, Elisabeth and Lundholm, Kent},
title = {Prostaglandin E and prostacyclin receptor expression in tumor and
host tissues from MCG 101-bearing mice: A model with prostanoid-related
cachexia},
journal = {Int. J. Cancer},
year = {2005},
volume = {115},
pages = {582--590},
number = {4},
abstract = {Abstract 10.1002/ijc.20539.abs Preclinical and clinical studies in
our laboratory have suggested that prostaglandin (PG) E2 is involved
in anorexia and cachexia development, although the role of COX pathways
on the pathogenesis of cancer cachexia remains to be clarified. Expressions
of PGE (EP1, EP2, EP3α,β,γ and EP4) and PGI (IP) receptors in
the central nervous system (brain cortex, hypothalamus and brain
stem), in peripheral (liver, white adipose tissue and skeletal muscle)
and tumor tissue from MCG-101-bearing mice with and without indomethacin
treatment were investigated by RT-PCR and immunohistochemistry. Expression
of EP1 in the liver and EP4 receptor in white adipose tissue were
upregulated and responded to indomethacin treatment, while downregulated
expression of EP3 in skeletal muscle from tumor-bearing mice was
unresponsive to indomethacin treatment despite improved carcass weight.
Expression of EP and IP receptors in brain and tumor tissue from
tumor-bearing mice were neither related nor responsive to systemic
PGE2 levels including increased IL-1bβ, IL-6 and TNF-aα host activities.
The expression IP receptor in CNS, peripheral tissue and tumor tissue
was unchanged by cachexia development. Our results suggest that transcription
of EP receptors in liver, fat and skeletal muscle tissue may be a
control level for host metabolic alterations during tumor progression,
while overall EP and IP receptor expression in CNS did not indicate
an important control level for appetite regulation in MCG 101-bearing
mice despite prostanoid related anorexia. © 2005 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {anorexia, EP receptor, cachexia},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.20539}
}
@ARTICLE{Wang2007c,
author = {Wang, Weipeng and Ni, Kunyi and Zhou, Guohua},
title = {Association of IL1B polymorphisms with gastric cancer in a Chinese
population},
journal = {Clinical Biochemistry},
year = {2007},
volume = {40},
pages = {218--225},
number = {3-4},
month = feb,
abstract = {Objectives: To investigate the association between IL1B polymorphisms
and risk of gastric cancer in a Chinese population, seven SNPs in
the IL1B gene were selected for this study.Methods: A multiplex genotyping
method, which is based on adapter ligation and allele-specific amplification,
was established to type seven SNPs on the IL1B gene simultaneously.
One hundred and forty-one non-cancer outpatients and 97 patients
with gastric cancer were genotyped, and the relation between IL1B
polymorphisms and gastric cancer was statistically analyzed.Results:
The seven SNPs were successfully typed and the results were consistent
with those obtained by both Sanger's sequencing and PCR-RFLP. Handling
with statistical analysis, we observed significantly different genotype
frequencies of 0794C > T ([chi]2 = 6.11, P = 0.05), 1274C > T ([chi]2 = 6.86,
P = 0.03) and 2143T > C ([chi]2 = 6.86, P=0.03) between patients
and controls.Conclusion: ALM-ASA is a potential method for multiplex
SNP typing with a low consumption of genomic DNA. SNPs 0794C > T,
1274C > T, and 2143T > C are associated with gastric cancer.},
issn = {0009-9120},
keywords = {Risk association, Gastric cancer, Polymorphisms, IL1B, ALM-ASA},
url = {http://www.sciencedirect.com/science/article/B6TDD-4MD2TC7-6/2/a891d76d15fd661e971ac099668525f0}
}
@ARTICLE{Wang2008g,
author = {Wang, Weipeng and Sun, Wenming and Wu, Wenjuan and Zhou, Guohua},
title = {Improved adapter-ligation-mediated allele-specific amplification
for multiplex genotyping by using software},
journal = {ELECTROPHORESIS},
year = {2008},
volume = {29},
pages = {1490--1501},
number = {7},
abstract = {Abstract Adapter-ligation-mediated allele-specific amplification (ALM-ASA)
is a potential method for multiplex SNPs typing at an ultra low cost.
Here, we describe a kind of software, which designs allele-specific
primers for ALM-ASA assay on multiplex SNPs. DNA sequences containing
SNPs of interest are submitted into the software which contains various
endonucleases for options. Based on the SNP sequence information
and the selected endonucleases, the software is capable of automatically
generating sets of information needed to perform genotyping experiments.
Each set contains a suitable endonuclease, qualified allele-specific
primers with orientations and melting temperatures, sizes of allele-specific
amplicons, and gel electropherograms simulated according to the sizes
of the allele-specific amplicons and the mobility of DNA fragments
in 2% agarose gel. Seven SNPs in the arylamines N-acetyltransferase
2 (NAT2) gene, five SNPs in the BRCA1 gene, five SNPs in the COMT
gene, six SNPs in the CYP2E1 gene, five SNPs in the MPO gene, and
six SNPs in the NRG1 gene were selected for evaluating the software.
Without extra optimization, seven SNPs in the NAT2 gene were successfully
genotyped for genomic DNA samples from 127 individuals by using the
first set of allele-specific primers yielded by the software. Although
several steps are used in the ALM-ASA assay, the whole genotyping
process can be completed within 3 h by optimizing each step. Profiting
from the software, the ALM-ASA assay is easy-to-perform, labor-saving,
and accurate.},
issn = {1522-2683},
keywords = {Adapter-ligaton-mediated allele-specific amplification, Arylamines
N-acetyltransferase 2, Multiplex genotyping, Single nucleotide polymorphism,
SNiPdesigner},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200700619}
}
@ARTICLE{Wang2011d,
author = {Wang, Wei-Bei and Levy, David E. and Lee, Chien-Kuo},
title = {STAT3 Negatively Regulates Type I IFN-Mediated Antiviral Response},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {2578-2585},
number = {5},
abstract = {Type I IFNs are crucial cytokines of innate immunity for combating
viral infections. Signaling through type I IFN receptors triggers
the activation of STAT proteins, including STAT1, STAT2, and STAT3.
Although an essential role of STAT1 and STAT2 for type I IFN-induced
antiviral response has been well established by studies of gene-targeted
mice and human mutations, the role of STAT3 for this response remains
unclear. Using gain-of-function and loss-of-function approaches,
we demonstrated that STAT3 negatively regulates type I IFN-mediated
response. STAT3 knockdown or knockout cells displayed enhanced gene
expression and antiviral activity in response to IFN-/{beta}. Restoration
of STAT3 to STAT3KO cells resulted in attenuation of the response.
Upon viral infection, increased type I IFN production in STAT3KO
cells resulted in enhanced STAT activation and ISG expression. One
mechanism for the enhanced IFN production and response in the absence
of STAT3 might operate through an MDA5-dependent manner. STAT3 also
appeared to suppress IFN response directly in a manner dependent
on its N-terminal domain and independent of its function as a transcriptional
factor. Taken together, these results define STAT3 as a negative
regulator of type I IFN response and provide a therapeutic target
for viral infections.},
doi = {10.4049/jimmunol.1004128},
eprint = {http://www.jimmunol.org/cgi/reprint/187/5/2578.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/5/2578}
}
@ARTICLE{Wang2008h,
author = {Wang, Wan-Heng and McNatt, Loretta G. and Pang, Iok-Hou and Hellberg,
Peggy E. and Fingert, John H. and McCartney, Mitchell D. and Clark,
Abbot F.},
title = {Increased Expression of Serum Amyloid A in Glaucoma and Its Effect
on Intraocular Pressure},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {1916--1923},
number = {5},
month = may,
abstract = {PURPOSE. To search for and validate potential molecular pathogenic
mechanisms in the trabecular meshwork (TM) responsible for the elevated
intraocular pressure (IOP) associated with glaucoma. METHODS. Gene
chip arrays were used to identify differential gene expression in
glaucomatous TM tissues. Serum amyloid A (SAA) upregulation was subsequently
confirmed with quantitative PCR (QPCR) and ELISA. The effect of SAA
on gene expression of cultured human TM cells was tested with gene
chip arrays and verified with ELISA, and its effect on IOP was evaluated
in the human ocular perfusion organ culture. RESULTS. Microarray
analysis showed that the expression of SAA2 was increased in TM tissues
from donors with glaucoma. This finding was subsequently confirmed
by QPCR. The SAA mRNA levels were increased in glaucoma TM tissues
by more than 5-fold (P < 0.05) and in cultured TM cells derived from
donors with glaucoma by 25-fold (P < 0.05) compared with controls.
SAA protein levels in the TM of glaucoma patients were also significantly
(P < 0.05) elevated by 2.9-fold. Treatment of cultured human TM cells
with recombinant SAA affected gene expression, including a 22-fold
up-regulation of interleukin-8 (P < 0.001). SAA increased IOP by
approximately 40% (P < 0.05) in the human ocular perfusion organ
culture without any observable changes in the morphology of the tissues
involved in aqueous outflow. CONCLUSIONS. These findings indicate
that SAA, which is an acute-phase apolipoprotein that plays important
roles in infection, inflammation, and tissue repair, may contribute
to the pathogenic changes to the TM in glaucoma.},
url = {http://www.iovs.org/cgi/content/abstract/49/5/1916}
}
@ARTICLE{Wang2006d,
author = {Wang, Wei-peng and Ni, Kun-yi and Zhou, Guo-hua},
title = {Multiplex single nucleotide polymorphism genotyping by adapter ligation-mediated
allele-specific amplification},
journal = {Analytical Biochemistry},
year = {2006},
volume = {355},
pages = {240--248},
number = {2},
month = aug,
abstract = {An improved approach for increasing the multiplex level of single
nucleotide polymorphism (SNP) typing by adapter ligation-mediated
allele-specific amplification (ALM-ASA) has been developed. Based
on an adapter ligation, each reaction requires n allele-specific
primers plus an adapter-specific primer that is common for all SNPs.
Thus, only n + 1 primers are used for an n-plex PCR amplification.
The specificity of ALM-ASA was increased by a special design of the
adapter structure and PCR suppression. Given that the genetic polymorphisms
in the liver enzyme cytochrome P450 CYP2D6 (debrisoquine 4-hydroxylase)
have profound effects on responses of individuals to a particular
drug, we selected 17 SNPs in the CYP2D6 gene as an example for the
multiplex SNP typing. Without extensive optimization, we successfully
typed 17-plex SNPs in the CYP2D6 gene by ALM-ASA. The results for
genotyping 70 different genome samples by the 17-plex ALM-ASA were
completely consistent with those obtained by both Sanger's sequencing
and PCR restriction fragment length polymorphism (PCR-RFLP) analysis.
ALM-ASA is a potential method for SNP typing at an ultra-low cost
because of a high multiplex level and a simple optimization step
for PCR. High-throughput SNP typing could be readily realized by
coupling ALM-ASA with a well-developed automation device for sample
processing.},
issn = {0003-2697},
keywords = {SNP, Genotyping, Adapter, ALM-ASA, CYP2D6},
url = {http://www.sciencedirect.com/science/article/B6W9V-4JWFBVJ-1/2/2c13dab94c965f6dc064fd256c0078c5}
}
@ARTICLE{Wang2009m,
author = {Wang, Wei-peng and Zhang, Rui-hong and Wu, Ping and Wang, Sen and
Li, Rong},
title = {Estimation of allele frequency in pooled DNA by using PCR-RFLP combined
with microchip electrophoresis},
journal = {Journal of Chromatography B},
year = {2009},
volume = {877},
pages = {1603--1606},
number = {14-15},
month = may,
abstract = {Biallelic marker, most commonly single nucleotide polymorphism (SNP),
is widely utilized in genetic association analysis, which can be
speeded up by estimating allele frequency in pooled DNA instead of
individual genotyping. Several methods have shown high accuracy and
precision for allele frequency estimation in pools. Here, we explored
PCR restriction fragment length polymorphism (PCR-RFLP) combined
with microchip electrophoresis as a possible strategy for allele
frequency estimation in DNA pools. We have used the commercial available
Agilent 2100 microchip electrophoresis analysis system for quantifying
the enzymatically digested DNA fragments and the fluorescence intensities
to estimate the allele frequencies in the DNA pools. In this study,
we have estimated the allele frequencies of five SNPs in a DNA pool
composed of 141 previously genotyped health controls and a DNA pool
composed of 96 previously genotyped gastric cancer patients with
a frequency representation of 10-90% for the variant allele. Our
studies show that accurate, quantitative data on allele frequencies,
suitable for investigating the association of SNPs with complex disorders,
can be estimated from pooled DNA samples by using this assay. This
approach, being independent of the number of samples, promises to
drastically reduce the labor and cost of genotyping in the initial
association analysis.},
issn = {1570-0232},
keywords = {Allele frequency, Pool, SNP, PCR-RFLP, Microchip electrophoresis},
url = {http://www.sciencedirect.com/science/article/B6X0P-4W15KTP-3/2/7b94b28014011c076211a69471b2741f}
}
@ARTICLE{Wang2008i,
author = {Wang, Wang-Xia and Rajeev, Bernard W. and Stromberg, Arnold J. and
Ren, Na and Tang, Guiliang and Huang, Qingwei and Rigoutsos, Isidore
and Nelson, Peter T.},
title = {The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's
Disease and May Accelerate Disease Progression through Regulation
of {beta}-Site Amyloid Precursor Protein-Cleaving Enzyme 1},
journal = {J. Neurosci.},
year = {2008},
volume = {28},
pages = {1213--1223},
number = {5},
month = jan,
abstract = {MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional
gene regulation in a sequence-specific manner. However, little is
understood about the role(s) of miRNAs in Alzheimer's disease (AD).
We used miRNA expression microarrays on RNA extracted from human
brain tissue from the University of Kentucky Alzheimer's Disease
Center Brain Bank with near-optimal clinicopathological correlation.
Cases were separated into four groups: elderly nondemented with negligible
AD-type pathology, nondemented with incipient AD pathology, mild
cognitive impairment (MCI) with moderate AD pathology, and AD. Among
the AD-related miRNA expression changes, miR-107 was exceptional
because miR-107 levels decreased significantly even in patients with
the earliest stages of pathology. In situ hybridization with cross-comparison
to neuropathology demonstrated that particular cerebral cortical
laminas involved by AD pathology exhibit diminished neuronal miR-107
expression. Computational analysis predicted that the 3'-untranslated
region (UTR) of {beta}-site amyloid precursor protein-cleaving enzyme
1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA
material analyzed on miRNA microarrays, mRNA expression profiling
was performed using Affymetrix Exon Array microarrays on nondemented,
MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107
levels decreased in the progression of AD. Cell culture reporter
assays performed with a subset of the predicted miR-107 binding sites
indicate the presence of at least one physiological miR-107 miRNA
recognition sequence in the 3'-UTR of BACE1 mRNA. Together, the coordinated
application of miRNA profiling, Affymetrix microarrays, new bioinformatics
predictions, in situ hybridization, and biochemical validation indicate
that miR-107 may be involved in accelerated disease progression through
regulation of BACE1.},
url = {http://www.jneurosci.org/cgi/content/abstract/28/5/1213}
}
@ARTICLE{Wang2008j,
author = {Wang, Wang-Xia and Wilfred, Bernard R. and Baldwin, Donald A. and
Isett, R. Benjamin and Ren, Na and Stromberg, Arnold and Nelson,
Peter T.},
title = {Focus on RNA isolation: Obtaining RNA for microRNA (miRNA) expression
profiling analyses of neural tissue},
journal = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},
year = {2008},
volume = {1779},
pages = {749--757},
number = {11},
month = nov,
abstract = {MicroRNAs (miRNAs) are present in all known plant and animal tissues
and appear to be somewhat concentrated in the mammalian nervous system.
Many different miRNA expression profiling platforms have been described.
However, relatively little research has been published to establish
the importance of [`]upstream' variables in RNA isolation for neural
miRNA expression profiling. We tested whether apparent changes in
miRNA expression profiles may be associated with tissue processing,
RNA isolation techniques, or different cell types in the sample.
RNA isolation was performed on a single brain sample using eight
different RNA isolation methods, and results were correlated using
a conventional miRNA microarray and then cross-referenced to Northern
blots. Differing results were seen between samples obtained using
different RNA isolation techniques and between microarray and Northern
blot results. Another complication of miRNA microarrays is tissue-level
heterogeneity of cellular composition. To investigate this phenomenon,
miRNA expression profiles were determined and compared between highly-purified
primary cerebral cortical cell preparations of rat primary E15-E18
neurons versus rat primary E15-E18 astrocytes. Finally, to assess
the importance of dissecting human brain gray matter from subjacent
white matter in cerebral cortical studies, miRNA expression profiles
were compared between gray matter and immediately contiguous white
matter. The results suggest that for microarray studies, cellular
composition is important, and dissecting white matter from gray matter
improves the specificity of the results. Based on these data, recommendations
for miRNA expression profiling in neural tissues, and considerations
worthy of further study, are discussed.},
booktitle = {MicroRNA},
issn = {1874-9399},
keywords = {miRNAs, microRNAs, Brain, Neuron, Astrocyte, Microarray, Northern,
Human, Alzheimer's disease, RNA isolation},
url = {http://www.sciencedirect.com/science/article/B8JH3-4RTW41V-1/2/87659cb83c9ba59318b9045e20f7eaac}
}
@ARTICLE{Wang2010a,
author = {Wang, Xinkun and Bao, Xiaodong and Pal, Ranu and Agbas, Abdulbaki
and Michaelis, Elias},
title = {Transcriptomic responses in mouse brain exposed to chronic excess
of the neurotransmitter glutamate},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {360},
number = {1},
abstract = {BACKGROUND:Increases during aging in extracellular levels of glutamate
(Glu), the major excitatory neurotransmitter in the brain, may be
linked to chronic neurodegenerative diseases. Little is known about
the molecular responses of neurons to chronic, moderate increases
in Glu levels. Genome-wide gene expression in brain hippocampus was
examined in a unique transgenic (Tg) mouse model that exhibits moderate
Glu hyperactivity throughout the lifespan, the neuronal Glutamate
dehydrogenase (Glud1) mouse, and littermate 9 month-old wild type
mice.RESULTS:Integrated bioinformatic analyses on transcriptomic
data were used to identify bio-functions, pathways and gene networks
underlying neuronal responses to increased Glu synaptic release.
Bio-functions and pathways up-regulated in Tg mice were those associated
with oxidative stress, cell injury, inflammation, nervous system
development, neuronal growth, and synaptic transmission. Increased
gene expression in these functions and pathways indicated apparent
compensatory responses offering protection against stress, promoting
growth of neuronal processes (neurites) and re-establishment of synapses.
The transcription of a key gene in the neurite growth network, the
kinase Ptk2b, was significantly up-regulated in Tg mice as was the
activated (phosphorylated) form of the protein. In addition to genes
related to neurite growth and synaptic development, those associated
with neuronal vesicle trafficking in the Huntington's disease signalling
pathway, were also up-regulated.CONCLUSIONS:This is the first study
attempting to define neuronal gene expression patterns in response
to chronic, endogenous Glu hyperactivity at brain synapses. The patterns
observed were characterized by a combination of responses to stress
and stimulation of nerve growth, intracellular transport and recovery.},
doi = {10.1186/1471-2164-11-360},
issn = {1471-2164},
pubmedid = {20529287},
url = {http://www.biomedcentral.com/1471-2164/11/360}
}
@ARTICLE{Wang2009n,
author = {Wang, Xiaoling and Chinnam, Meenalakshmi and Wang, Jianmin and Wang,
Yanqing and Zhang, Xiaojing and Marcon, Edyta and Moens, Peter and
Goodrich, David W.},
title = {Thoc1 Deficiency Compromises Gene Expression Necessary for Normal
Testis Development in the Mouse},
journal = {Mol. Cell. Biol.},
year = {2009},
volume = {29},
pages = {2794--2803},
number = {10},
month = may,
abstract = {Accumulating evidence suggests that regulation of RNA processing through
an RNP-driven mechanism is important for coordinated gene expression.
This hypothesis predicts that defects in RNP biogenesis will adversely
affect the elaboration of specific gene expression programs. To explore
the role of RNP biogenesis on mammalian development, we have characterized
the phenotype of mice hypomorphic for Thoc1. Thoc1 encodes an essential
component of the evolutionarily conserved TREX complex. TREX accompanies
the elongating RNA polymerase II and facilitates RNP assembly and
recruitment of RNA processing factors. Hypomorphic Thoc1 mice are
viable despite significantly reduced Thoc1 expression in the tissues
examined. While most tissues of Thoc1-deficient mice appear to develop
and function normally, gametogenesis is severely compromised. Male
infertility is associated with a loss in spermatocyte viability and
abnormal endocrine signaling. We suggest that loss of spermatocyte
viability is a consequence of defects in the expression of genes
required for normal differentiation of cell types within the testes.
A number of the genes affected appear to be direct targets for regulation
by Thoc1. These findings support the notion that Thoc1-mediated RNP
assembly contributes to the coordinated expression of genes necessary
for normal differentiation and development in vivo.},
url = {http://mcb.asm.org/cgi/content/abstract/29/10/2794}
}
@ARTICLE{Wang2009o,
author = {Wang, Xingya and Colby, Jennifer K.L. and Rengel, Robert C. and Fischer,
Susan M. and Clinton, Steven K. and Klein, Russell D.},
title = {Overexpression of cyclooxygenase-2 (COX-2) in the mouse urinary bladder
induces the expression of immune- and cell proliferation-related
genes},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {1--13},
number = {1},
abstract = {Abstract 10.1002/mc.20449.abs The mechanisms whereby cyclooxygenase-2
(COX-2) overexpression may contribute to bladder carcinogenesis remain
unknown. We recently developed a transgenic mouse model overexpressing
COX-2 under the control of a bovine keratin 5 (BK5) promoter causing
a high incidence of transitional cell hyperplasia (TCH) in the bladder
with a proportion of lesions progressing to invasive carcinoma. Microarray
gene analysis was employed to determine the effects of COX-2 overexpression
on gene expression profiles in the urinary bladder. Statistical analysis
revealed that 70 genes were upregulated and 60 were downregulated
by twofold or more in bladders from transgenic compared to wild-type
mice. Expression Analysis Systematic Explorer (EASE) analysis revealed
that genes associated with Immune/Stress Response and Cell Cycle/Proliferation
biological processes were overexpressed in the transgenic mice. Relevant
downregulated genes included three transforming growth factor (TGF)-β
related genes, Tgfb2, Tgfb3, and Tgfbi. The growth factor epiregulin
was the most highly induced gene among those validated by qRT-PCR
in TCH of BK5.COX-2 mouse bladders in parallel with increased staining
for Ki67. Prostaglandin E2 (PGE2) directly induced the expression
of epiregulin mRNA in bladders from wild-type FVB mice ex vivo. We
further determined that recombinant epiregulin increased both cell
proliferation and Erk phosphorylation in UMUC-3 bladder cancer cells.
These results indicate that the response of the mouse urinary bladder
to elevated COX-2 expression includes enhanced inflammatory response
and induction of cell proliferation. The growth factor epiregulin
may play a role in bladder carcinogenesis and may serve as a novel
target for the prevention and treatment of bladder cancer. © 2008
Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {COX-2 transgenic mouse, bladder, gene profile, epiregulin},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20449}
}
@ARTICLE{Wang2008k,
author = {Wang, Xingya and Colby, Jennifer K.L. and Yang, Peiying and Fischer,
Susan M. and Newman, Robert A. and Klein, Russell D.},
title = {The resistance to the tumor suppressive effects of COX inhibitors
and COX-2 gene disruption in TRAMP mice is associated with the loss
of COX expression in prostate tissue},
journal = {Carcinogenesis},
year = {2008},
volume = {29},
pages = {120--128},
number = {1},
month = jan,
abstract = {Over-expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 has
been demonstrated to play a significant role in the tumorigenesis
of colon, lung, breast, bladder and skin. However, inconsistent and
controversial reports on the expression and activity of COX-2 in
prostate cancer raised the question of whether COX-2 plays a pivotal
role in prostate carcinogenesis. To address this question, we examined
the effects of COX-2 inhibition on prostate tumorigenesis in the
transgenic adenocarcinoma mouse prostate (TRAMP) model. Three-week-old
TRAMP mice were fed control, celecoxib- or indomethacin-supplemented
diets for 27 weeks. A TRAMP/COX-2 knockout mouse model was also generated
to determine the effects of the loss of the COX-2 gene on prostate
tumorigenesis in TRAMP mice. These studies demonstrated that neither
non-steroidal anti-inflammatory drugs (NSAIDs) nor genetic disruption
of COX-2 was inhibitory in terms of tumor and metastases incidence,
lobe weight or types of pathological lesions. A careful analysis
of wild-type and TRAMP tissues was undertaken for the expression
of cyclooxygenase-1 (COX-1) and COX-2 using immunoblotting, quantitative
real time polymerase chain reaction (qRT-PCR) and immunohistochemistry
approaches in TRAMP dorsal prostate tissue from 10- and 16-week-old,
as well as tumor from 30-week-old mice. We found that the expression
of COX-1 and COX-2 dramatically decreased during TRAMP carcinogenesis.
Using the probasin promoter, a COX-2 over-expressing mouse model
was also generated but failed to show any pathology in any of the
prostate lobes. Collectively, our results suggest that COX-2 may
not play a tumorigenic role during prostate carcinogenesis in the
TRAMP model.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/29/1/120}
}
@ARTICLE{Wang2011b,
author = {Wang, Xingya and Kingsley, Philip J. and Marnett, Larry J. and Eling,
Thomas E.},
title = {The Role of NAG-1/GDF15 in the Inhibition of Intestinal Polyps in
APC/Min Mice by Sulindac},
journal = {Cancer Prevention Research},
year = {2011},
volume = {4},
pages = {150--160},
number = {1},
month = jan,
abstract = {The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID)
are assumed to be due to the inhibition of COX activity, but COX-independent
mechanisms may also play an important role. NSAID-activated gene
(NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities.
To determine the contribution of COX-2 inhibition and NAG-1/GDF15
expression to the prevention of colon carcinogenesis by NSAIDs, we
evaluated several sulindac derivatives [des-methyl (DM)-sulindac
sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity.
Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15
in HCT116 cells as determined by quantitative real-time PCR and Western
blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac.
Only sulindac significantly inhibited tumor formation inAPC/Min mice.
To determine the pharmacokinetic properties of sulindac and DM-sulindac
in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac
at 80, 160, and 320 ppm. High-performance liquid chromatography analysis
revealed that the conversion of DM-sulindac to DM-sulindac sulfide
(active form) was less efficient than the conversion of sulindac
to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac
sulfide accumulated in intestinal and colon tissues in comparison
with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the
liver of sulindac-fed mice but not in the DM-sulindac-fed mice. Collectively,
our results suggest that the tumor-inhibitory effects of sulindac
in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in
the liver. Our study also suggests that pharmacologic properties
should be carefully evaluated when developing drug candidates. Cancer
Prev Res; 4(1); 150-60. (C)2011 AACR.},
comment = {10.1158/1940-6207.CAPR-10-0196},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/4/1/150}
}
@ARTICLE{Wang2007d,
author = {Wang, Xingya and Klein, Russell D.},
title = {Prostaglandin E2 induces vascular endothelial growth factor secretion
in prostate cancer cells through EP2 receptor-mediated cAMP pathway},
journal = {Mol. Carcinog.},
year = {2007},
volume = {46},
pages = {912--923},
number = {11},
abstract = {Abstract 10.1002/mc.20320.abs Prostaglandin E2 (PGE2) has been shown
to induce expression of vascular endothelial growth factor (VEGF)
and other signaling molecules in several cancers. PGE2 elicits its
functions though four G-protein coupled membrane receptors (EP1–4).
In this study, we investigated the role of EP receptors in PGE2-induced
molecular events in prostate cancer cells. qRT-PCR analysis revealed
that PC-3 cells express a substantially higher level of EP2 and moderately
higher EP4 than DU145 and LNCaP cells. LNCaP cells had virtually
no detectable EP2 mRNA. EP1 and EP3 mRNAs were not detected in these
cells. Treatment of prostate cancer cells with PGE2 (1 nM–10 µM)
increased both VEGF secretion and cyclic adenosine monophosphate
(cAMP) production. Levels of induction in PC-3 cells were greater
than in DU145 and LNCaP cells. The selective EP2 agonist CAY10399
also significantly increased VEGF secretion and cAMP production in
PC-3 cells, but not in DU145 and LNCaP cells. Moreover, PGE2 and
CAY10399 increased mitogen activated protein kinase/extracellular
signal regulated kinase (MAPK/Erk) and Akt phosphorylation in PC-3
and DU145 cells, but not in LNCaP cells. However, neither the MAPK/Erk
inhibitor U0126 nor the PI3K/Akt inhibitor LY294002 abolished PGE2-induced
VEGF secretion in PC-3 cells. We further demonstrated that the adenylate
cyclase activator forskolin and the cAMP anologue 8-bromo-cAMP mimicked
the effects of PGE2 on VEGF secretion in PC-3 cells. Meanwhile, the
adenylate cyclase inhibitor 2′5′-dideoxyadenosine, at concentrations
that inhibited PGE2-induced cAMP, significantly blocked PGE2-induced
VEGF secretion in PC-3 cells. We conclude that PGE2-induced VEGF
secretion in prostate cancer cells is mediated through EP2-, and
possibly EP4-, dependent cAMP signaling pathways. © 2007 Wiley-Liss,
Inc.},
issn = {1098-2744},
keywords = {PGE2, EP2 receptor, VEGF, prostate cancer cells},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20320}
}
@ARTICLE{Wang2010i,
author = {Wang, Xinkang and Liu, Xiaorong and Zhan, Yutian and LaVallie, Edward
R. and DiBlasio-Smith, Liz and Collins-Racie, Lisa and Mounts, William
M. and Rutkowski, J. Lynn and Xu, Xin and Goltsman, Ilia and Abassi,
Zaid and Winaver, Joseph and Feuerstein, Giora Z.},
title = {Pharmacogenomic, Physiological, and Biochemical Investigations on
Safety and Efficacy Biomarkers Associated with the Peroxisome Proliferator-Activated
Receptor-{gamma} Activator Rosiglitazone in Rodents: A Translational
Medicine Investigation},
journal = {J. Pharmacol. Exp. Ther.},
year = {2010},
volume = {334},
pages = {820--829},
number = {3},
month = sep,
abstract = {Peroxisome proliferator-activated receptor (PPAR)-{gamma} modulators,
a class of antidiabetic drugs, have been associated with cardiovascular
risks in type 2 diabetes in humans. The objective of this study was
to explore possible cardiovascular risk biomarkers associated with
PPAR-{gamma} in rodents that could provide an alert for risk to humans.
Normal, myocardial infarction-induced heart failure (HF) or Zucker
diabetic fatty (ZDF) rats were used. Rats (n = 5-6) were treated
with either vehicle or rosiglitazone (RGZ; 3 or 45 mg/kg/day p.o.)
for 4 weeks. Biomarkers for potential cardiovascular risks were assessed,
including 1) ultrasound for cardiac structure and function; 2) neuroendocrine
and hormonal plasma biomarkers of cardiovascular risk; 3) pharmacogenomic
profiling of cardiac and renal tissue by targeted tissue low-density
gene array representing ion channels and transporters, and components
of the renin-angiotensin-aldosterone system; and 4) immunohistochemistry
for cardiac fibrosis, hypertrophy, and inflammation (macrophages
and tumor necrosis factor-{alpha}). HF was confirmed by increase
in cardiac brain natriuretic peptide expression (p < 0.01) and echocardiography.
Adequate exposure of RGZ was confirmed by pharmacokinetics (plasma
drug levels) and the pharmacodynamic biomarker adiponectin. In normal
or HF rats, RGZ had no negative effects on any of the biomarkers
investigated. Similarly, RGZ had no significant effects on gene expression
except for the increase in interleukin-6 mRNA expression in the heart
and decrease in epithelial sodium channel {beta} in the kidney. In
contrast, echocardiography showed improved cardiac structure and
function after RGZ in ZDF rats. Taken together, this study suggests
a limited predictive power of these preclinical models in respect
to observed clinical adverse effects associated with RGZ.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/334/3/820}
}
@ARTICLE{Wang2007e,
author = {Wang, Xinkun and Pal, Ranu and Chen, Xue-wen and Kumar, Keshava N.
and Kim, Ok-Jin and Michaelis, Elias K.},
title = {Genome-wide transcriptome profiling of region-specific vulnerability
to oxidative stress in the hippocampus},
journal = {Genomics},
year = {2007},
volume = {90},
pages = {201--212},
number = {2},
month = aug,
abstract = {Neurons in the hippocampal CA1 region are particularly sensitive to
oxidative stress (OS), whereas those in CA3 are resistant. To uncover
mechanisms for selective CA1 vulnerability to OS, we treated organotypic
hippocampal slices with duroquinone and compared transcriptional
profiles of CA1 vs CA3 cells at various intervals. Gene Ontology
and Biological Pathway analyses of differentially expressed genes
showed that at all time points, CA1 had higher transcriptional activity
for stress/inflammatory response, transition metal transport, ferroxidase,
and presynaptic signaling activity, while CA3 had higher GABA-signaling,
postsynaptic, and calcium and potassium channel activity. Real-time
PCR and immunoblots confirmed the transcriptome data and the induction
of OS by duroquinone in both hippocampal regions. Our functional
genomics approach has identified in CA1 cells molecular pathways
as well as unique genes, such as guanosine deaminase, lipocalin 2,
synaptotagmin 4, and latrophilin 2, whose time-dependent induction
following the initiation of OS may represent attempts at neurite
outgrowth, synaptic recovery, and resistance against OS.},
issn = {0888-7543},
keywords = {Hippocampus, CA1, CA3, Oxidative stress, Inflammation, Neurite outgrowth,
Gene expression profiling},
url = {http://www.sciencedirect.com/science/article/B6WG1-4NWW6J6-1/2/bab23b611f18b8ad6a53455464c63608}
}
@ARTICLE{Wang2011g,
author = {Wang, Xiaojing and Slebos, Robbert J. C. and Wang, Dong and Halvey,
Patrick J. and Tabb, David L. and Liebler, Daniel C. and Zhang, Bing},
title = {Protein Identification Using Customized Protein Sequence Databases
Derived from RNA-Seq Data},
journal = {Journal of Proteome Research},
year = {2011},
volume = {0},
pages = {null},
number = {0},
abstract = { The standard shotgun proteomics data analysis strategy relies on
searching MS/MS spectra against a context-independent protein sequence
database derived from the complete genome sequence of an organism.
Because transcriptome sequence analysis (RNA-Seq) promises an unbiased
and comprehensive picture of the transcriptome, we reason that a
sample-specific protein database derived from RNA-Seq data can better
approximate the real protein pool in the sample and thus improve
protein identification. In this study, we have developed a two-step
strategy for building sample-specific protein databases from RNA-Seq
data. First, the database size is reduced by eliminating unexpressed
or lowly expressed genes according to transcript quantification.
Second, high-quality nonsynonymous coding single nucleotide variations
(SNVs) are identified based on RNA-Seq data, and corresponding protein
variants are added to the database. Using RNA-Seq and shotgun proteomics
data from two colorectal cancer cell lines SW480 and RKO, we demonstrated
that customized protein sequence databases could significantly increase
the sensitivity of peptide identification, reduce ambiguity in protein
assembly, and enable the detection of known and novel peptide variants.
Thus, sample-specific databases from RNA-Seq data can enable more
sensitive and comprehensive protein discovery in shotgun proteomics
studies. },
doi = {10.1021/pr200766z},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/pr200766z},
url = {http://pubs.acs.org/doi/abs/10.1021/pr200766z}
}
@ARTICLE{Wang2010j,
author = {Wang, Xu and Soloway, Paul and Clark, Andrew},
title = {Paternally biased X inactivation in mouse neonatal brain},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R79},
number = {7},
abstract = {BACKGROUND:X inactivation in female eutherian mammals has long been
considered to occur at random in embryonic and postnatal tissues.
Methods for scoring allele-specific differential expression with
a high degree of accuracy have recently motivated a quantitative
reassessment of the randomness of X inactivation.RESULTS:After RNA-seq
data revealed what appeared to be a chromosome-wide bias toward under-expression
of paternal alleles in mouse tissue, we applied pyrosequencing to
mouse brain cDNA samples from reciprocal cross F1 progeny of divergent
strains and found a small but consistent and highly statistically
significant excess tendency to under-express the paternal X chromosome.CONCLUSIONS:The
bias toward paternal X inactivation is reminiscent of marsupials
(and extraembryonic tissues in eutherians), suggesting that there
may be retained an evolutionarily conserved epigenetic mark driving
the bias. Allelic bias in expression is also influenced by the sampling
effect of X inactivation and by cis-acting regulatory variation (eQTL),
and for each gene we quantify the contributions of these effects
in two different mouse strain combinations while controlling for
variability in Xce alleles. In addition, we propose an efficient
method to identify and confirm genes that escape X inactivation in
normal mice by directly comparing the allele-specific expression
ratio profile of multiple X-linked genes in multiple individuals.},
doi = {10.1186/gb-2010-11-7-r79},
issn = {1465-6906},
pubmedid = {20663224},
url = {http://genomebiology.com/2010/11/7/R79}
}
@ARTICLE{Wang2011z,
author = {Wang, Xu and Soloway, Paul D. and Clark, Andrew G.},
title = {A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq},
journal = {Genetics},
year = {2011},
volume = {189},
pages = {109-122},
number = {1},
abstract = {Many questions about the regulation, functional specialization, computational
prediction, and evolution of genomic imprinting would be better addressed
by having an exhaustive genome-wide catalog of genes that display
parent-of-origin differential expression. As a first-pass scan for
novel imprinted genes, we performed mRNA-seq experiments on embryonic
day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross
F1 progeny of AKR and PWD mouse strains and quantified the allele-specific
expression and the degree of parent-of-origin allelic imbalance.
We confirmed the imprinting status of 23 known imprinted genes in
the placenta and found that 12 genes reported previously to be imprinted
in other tissues are also imprinted in mouse placenta. Through a
well-replicated design using an orthogonal allelic-expression technology,
we verified 5 novel imprinted genes that were not previously known
to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3).
Our data suggest that most of the strongly imprinted genes have already
been identified, at least in the placenta, and that evidence supports
perhaps 100 additional weakly imprinted genes. Despite previous appearance
that the placenta tends to display an excess of maternally expressed
imprinted genes, with the addition of our validated set of placenta-imprinted
genes, this maternal bias has disappeared.},
doi = {10.1534/genetics.111.130088},
eprint = {http://www.genetics.org/cgi/reprint/189/1/109.pdf},
url = {http://www.genetics.org/cgi/content/abstract/189/1/109}
}
@ARTICLE{Wang2009p,
author = {Wang, Xinkun and Zaidi, Asma and Pal, Ranu and Garrett, Alexander
and Braceras, Rogelio and Chen, Xue-wen and Michaelis, Mary and Michaelis,
Elias},
title = {Genomic and biochemical approaches in the discovery of mechanisms
for selective neuronal vulnerability to oxidative stress},
journal = {BMC Neuroscience},
year = {2009},
volume = {10},
pages = {12},
number = {1},
abstract = {BACKGROUND:Oxidative stress (OS) is an important factor in brain aging
and neurodegenerative diseases. Certain neurons in different brain
regions exhibit selective vulnerability to OS. Currently little is
known about the underlying mechanisms of this selective neuronal
vulnerability. The purpose of this study was to identify endogenous
factors that predispose vulnerable neurons to OS by employing genomic
and biochemical approaches.RESULTS:In this report, using in vitro
neuronal cultures, ex vivo organotypic brain slice cultures and acute
brain slice preparations, we established that cerebellar granule
(CbG) and hippocampal CA1 neurons were significantly more sensitive
to OS (induced by paraquat) than cerebral cortical and hippocampal
CA3 neurons. To probe for intrinsic differences between in vivo vulnerable
(CA1 and CbG) and resistant (CA3 and cerebral cortex) neurons under
basal conditions, these neurons were collected by laser capture microdissection
from freshly excised brain sections (no OS treatment), and then subjected
to oligonucleotide microarray analysis. GeneChip-based transcriptomic
analyses revealed that vulnerable neurons had higher expression of
genes related to stress and immune response, and lower expression
of energy generation and signal transduction genes in comparison
with resistant neurons. Subsequent targeted biochemical analyses
confirmed the lower energy levels (in the form of ATP) in primary
CbG neurons compared with cortical neurons.CONCLUSION:Low energy
reserves and high intrinsic stress levels are two underlying factors
for neuronal selective vulnerability to OS. These mechanisms can
be targeted in the future for the protection of vulnerable neurons.},
doi = {10.1186/1471-2202-10-12},
issn = {1471-2202},
pubmedid = {19228403},
url = {http://www.biomedcentral.com/1471-2202/10/12}
}
@ARTICLE{Wang2007f,
author = {Wang, Xueqing and Zhu, Shiqian and Khan, Ikhlas A. and Dasmahapatra,
Asok K.},
title = {Ethanol attenuates Aldh9 mRNA expression in Japanese medaka (Oryzias
latipes) embryogenesis},
journal = {Comparative Biochemistry and Physiology Part B: Biochemistry and
Molecular Biology},
year = {2007},
volume = {146},
pages = {357--363},
number = {3},
month = mar,
abstract = {The mechanisms of teratogenic effects of ethanol in Japanese medaka
embryogenesis were investigated by testing the hypothesis that ethanol
or its metabolite ameliorates the expression of ethanol metabolizing
enzymes. We have previously demonstrated that ethanol is unable to
alter the expression pattern of alcohol dehydrogenase (ADH) mRNA,
the first enzyme of ethanol metabolism, in medaka embryos during
development. We, therefore, extended our investigation to aldehyde
dehydrogenase (ALDH) system, the next enzyme of alcohol metabolic
pathway. As the first step towards studying the regulation of Aldh
mRNA expression by ethanol, we have cloned a cDNA by reverse transcriptase
polymerase chain reaction (RT-PCR) from adult Japanese medaka (Oryzias
latipes) liver representing the medaka ALDH9 gene product, with a
coding region of 1515 nucleotides. The deduced amino acid sequences
share 81.2% identity with cod liver betaine aldehyde dehydrogenase
(BADH, EC 1.2.1.8), and 71.1% identity with human ALDH9A1 sequences.
RT-PCR analysis further showed that in adults Aldh9 mRNA is constitutively
expressed in all organs tested (brain, eye, gill, GI, heart, liver,
kidney, muscle, skin, testis and ovary). Using semi-quantitative
(rRT-PCR) and quantitative real time RT-PCR (qRT-PCR), we detected
Aldh9 mRNA at all time points of development and the expression was
lowest between ~ 1 and 8 h post-fertilization (hpf). Treatment of
the embryos with ethanol for 48 h post-fertilization (hpf) attenuates
(delayed) the expression of Aldh9 mRNA. This delayed expression of
Aldh9 mRNA by ethanol may enhance acetaldehyde concentration in the
embryo and induce teratogenesis during development.},
issn = {1096-4959},
keywords = {Aldehyde dehydrogenase, Development, Gene expression, Japanese medaka,
Teratogenesis, Embryogenesis, Ethanol},
url = {http://www.sciencedirect.com/science/article/B6T2R-4MD2TD7-4/2/ce68fbf727daa94bd8ac6882ee9be719}
}
@ARTICLE{Wang2011v,
author = {Wang, Xiaonan H. and Hu, Zhaoyong and Klein, Janet D. and Zhang,
Liping and Fang, Fude and Mitch, William E.},
title = {Decreased miR-29 Suppresses Myogenesis in CKD},
journal = {J. Am. Soc. Nephrol.},
year = {2011},
volume = {22},
pages = {2068-2076},
number = {11},
abstract = {The mechanisms underlying the muscle wasting that accompanies CKD
are not well understood. Animal models suggest that impaired differentiation
of muscle progenitor cells may contribute. Expression of the myogenesis-suppressing
transcription factor Ying Yang-1 increases in muscle of animals with
CKD, but the mechanism underlying this increased expression is unknown.
Here, we examined a profile of microRNAs in muscles from mice with
CKD and observed downregulation of both microRNA-29a (miR-29a) and
miR-29b. Because miR-29 has a complementary sequence to the 3'-untranslated
region of Ying Yang-1 mRNA, a decrease in miR-29 could increase Ying
Yang-1. We used adenovirus-mediated gene transfer to express miR-29
in C2C12 myoblasts and measured its effect on both Ying Yang-1 and
myoblast differentiation. An increase in miR-29 decreased the abundance
of Ying Yang-1 and improved the differentiation of myoblasts into
myotubes. Similarly, using myoblasts isolated from muscles of mice
with CKD, an increase in miR-29 improved differentiation of muscle
progenitor cells into myotubes. In conclusion, CKD suppresses miR-29
in muscle, which leads to higher expression of the transcription
factor Ying Yang-1, thereby suppressing myogenesis. These data suggest
a potential mechanism for the impaired muscle cell differentiation
associated with CKD.},
doi = {10.1681/ASN.2010121278},
eprint = {http://jasn.asnjournals.org/cgi/reprint/22/11/2068.pdf},
url = {http://jasn.asnjournals.org/cgi/content/abstract/22/11/2068}
}
@ARTICLE{Wang2006e,
author = {Wang, Xiu Jun and Hayes, John D. and Wolf, C. Roland},
title = {Generation of a Stable Antioxidant Response Element-Driven Reporter
Gene Cell Line and Its Use to Show Redox-Dependent Activation of
Nrf2 by Cancer Chemotherapeutic Agents},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {10983--10994},
number = {22},
month = nov,
abstract = {The NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes
that contain an antioxidant response element (ARE) in their promoters.
To investigate whether anticancer drugs can induce ARE-driven gene
expression, we have developed a stable human mammary MCF7-derived
reporter cell line called AREc32, which contains a luciferase gene
construct controlled by eight copies of the cis-element. In these
cells, luciferase activity was increased up to 50-fold following
treatment with 50 {micro}mol/L tert-butylhydroquinone (t-BHQ). Basal
and inducible luciferase activities in AREc32 cells were increased
by forced overexpression of Nrf2 and reduced by knockdown of endogenous
Nrf2 expression with RNA interference. Depletion of cellular reduced
glutathione (GSH) by treatment of AREc32 cells with L-buthionine-S,R-sulfoximine
(BSO) did not influence basal levels of luciferase activity, but
pretreatment with BSO augmented induction of luciferase activity
by t-BHQ. Induction of reporter activity by t-BHQ in AREc32 cells
was suppressed markedly by the antioxidants N-acetylcysteine and
GSH but only modestly by vitamins C or E, suggesting that ARE-luciferase
expression is induced primarily by thiol-active electrophiles rather
than free radicals. The anticancer drugs cisplatin, etoposide, mitoxantrone,
chlorambucil, melphalan, and carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea
(BCNU)] weakly induced luciferase activity in AREc32 cells. Moreover,
treatment of AREc32 cells with BSO immediately before exposure to
anticancer drugs enhanced induction of ARE-driven luciferase activity
by cisplatin, BCNU, chlorambucil, and melphalan and also induced
endogenous AKR1C (AKR1C refers to AKR1C1 and AKR1C2), a target gene
of Nrf2. Our findings show that Nrf2 can be activated by certain
anticancer agents, and this will influence the effectiveness of chemotherapy.
(Cancer Res 2006; 66(22): 10983-94)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/22/10983}
}
@ARTICLE{Wang2007g,
author = {Wang, Xi-De and Reeves, Karen and Luo, Feng and Xu, Li-An and Lee,
Francis and Clark, Edwin and Huang, Fei},
title = {Identification of candidate predictive and surrogate molecular markers
for dasatinib in prostate cancer: rationale for patient selection
and efficacy monitoring},
journal = {Genome Biology},
year = {2007},
volume = {8},
pages = {R255},
number = {11},
abstract = {BACKGROUND:Dasatinib is a potent, multi-targeted kinase inhibitor
that was recently approved for treatment of chronic myelogenous leukemia
resistant to imatinib. To aid the clinical development of dasatinib
in prostate cancer, we utilized preclinical models to identify potential
molecular markers for patient stratification and efficacy monitoring.RESULTS:Using
gene expression profiling, we first identified 174 genes whose expression
was highly correlated with in vitro sensitivity of 16 cell lines
and, thus, considered as candidate efficacy predictive markers. Among
these are important prostatic cell lineage markers, cytokeratin 5,
androgen receptor and prostate specific antigen. Our results indicate
that 'basal type' cell lines with high expression of cytokeratin
5 and low expression of androgen receptor or prostate specific antigen
are sensitive to dasatinib. To identify markers as surrogates for
biological activity, we treated cell lines with dasatinib and identified
genes whose expression was significantly modulated by the drug. Ten
genes, including that encoding urokinase-type plasminogen activator
(uPA), were found to not only be potential efficacy markers but also
to have reduced expression upon dasatinib treatment. The down-regulation
of uPA by dasatinib was drug-specific and correlated with the sensitivity
of cell lines to dasatinib. Furthermore, EphA2, a target of dasatinib,
was found to be a sensitivity biomarker.CONCLUSION:Using the gene
expression profiling approach and preclinical models, we have identified
prostatic biomarkers that are associated with sensitivity to dasatinib.
This study has provided a basis for clinical evaluation of a potential
dasatinib efficacy signature in prostate cancer.},
doi = {10.1186/gb-2007-8-11-r255},
issn = {1465-6906},
owner = {Meike Kuschel},
pubmedid = {18047674},
timestamp = {2010.04.07},
url = {http://genomebiology.com/2007/8/11/R255}
}
@ARTICLE{Wang2009q,
author = {Wang, Xiu-Hong and Cavell, Breeze E. and Syed Alwi, Sharifah S. and
Packham, Graham},
title = {Inhibition of hypoxia inducible factor by phenethyl isothiocyanate},
journal = {Biochemical Pharmacology},
year = {2009},
volume = {78},
pages = {261--272},
number = {3},
month = aug,
issn = {0006-2952},
keywords = {Hypoxia inducible factor, Angiogenesis, Phenethyl isothiocyanate,
Translation, Degradation},
url = {http://www.sciencedirect.com/science/article/B6T4P-4W38RD3-2/2/b0c14e843e5f1016491d908aac35a217}
}
@ARTICLE{Wang2010s,
author = {Wang, Xiao-Wei and Luan, Jun-Bo and Li, Jun-Min and Bao, Yan-Yuan
and Zhang, Chuan-Xi and Liu, Shu-Sheng},
title = {De novo characterization of a whitefly transcriptome and analysis
of its gene expression during development},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {400},
number = {1},
abstract = {BACKGROUND:Whitefly (Bemisia tabaci) causes extensive crop damage
throughout the world by feeding directly on plants and by vectoring
hundreds of species of begomoviruses. Yet little is understood about
its genes involved in development, insecticide resistance, host range
plasticity and virus transmission.RESULTS:To facilitate research
on whitefly, we present a method for de novo assembly of whitefly
transcriptome using short read sequencing technology (Illumina).
In a single run, we produced more than 43 million sequencing reads.
These reads were assembled into 168,900 unique sequences (mean size
= 266 bp) which represent more than 10-fold of all the whitefly sequences
deposited in the GenBank (as of March 2010). Based on similarity
search with known proteins, these analyses identified 27,290 sequences
with a cut-off E-value above 10-5. Assembled sequences were annotated
with gene descriptions, gene ontology and clusters of orthologous
group terms. In addition, we investigated the transcriptome changes
during whitefly development using a tag-based digital gene expression
(DGE) system. We obtained a sequencing depth of over 2.5 million
tags per sample and identified a large number of genes associated
with specific developmental stages and insecticide resistance.CONCLUSION:Our
data provides the most comprehensive sequence resource available
for whitefly study and demonstrates that the Illumina sequencing
allows de novo transcriptome assembly and gene expression analysis
in a species lacking genome information. We anticipate that next
generation sequencing technologies hold great potential for the study
of the transcriptome in other non-model organisms.},
doi = {10.1186/1471-2164-11-400},
issn = {1471-2164},
pubmedid = {20573269},
url = {http://www.biomedcentral.com/1471-2164/11/400}
}
@ARTICLE{Wang2011,
author = {Wang, Xiao-Wei and Luan, Jun-Bo and Li, Jun-Min and Su, Yun-Lin and
Xia, Jun and Liu, Shu-Sheng},
title = {Transcriptome analysis and comparison reveal divergence between two
invasive whitefly cryptic species},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {458},
number = {1},
abstract = {BACKGROUND:Invasive species are valuable model systems for examining
the evolutionary processes and molecular mechanisms associated with
their specific characteristics by comparison with closely related
species. Over the past 20 years, two species of the whitefly Bemisia
tabaci species complex, Middle East-Asia Minor 1 (MEAM1) and Mediterranean
(MED), have both spread from their origin Middle East/Mediterranean
to many countries despite their apparent differences in many life
history parameters. Previously, we have sequenced the transcriptome
of MED. In this study, we sequenced the transcriptome of MEAM1 and
took a comparative genomic approach to investigate the transcriptome
evolution and the genetic factors underlying the differences between
MEAM1 and MED.RESULTS:Using Illumina sequencing technology, we generated
17 million sequencing reads for MEAM1. These reads were assembled
into 57,741 unique sequences and 15,922 sequences were annotated
with an E-value above 10-5. Compared with the MED transcriptome,
we identified 3,585 pairs of high quality orthologous genes and inferred
their sequence divergences. The average differences in coding, 5'
untranslated and 3' untranslated region were 0.83%, 1.66% and 1.43%,
respectively. The level of sequence divergence provides additional
support to the proposition that MEAM1 and MED are two species. Based
on the ratio of nonsynonymous and synonymous substitutions, we identified
24 sequences that have evolved in response to positive selection.
Many of those genes are predicted to be involved in metabolism and
insecticide resistance which might contribute to the divergence of
the two whitefly species.CONCLUSIONS:Our data present a comprehensive
sequence comparison between the two invasive whitefly species. This
study will provide a road map for future investigations on the molecular
mechanisms underlying their biological differences.},
doi = {10.1186/1471-2164-12-458},
issn = {1471-2164},
pubmedid = {21939539},
url = {http://www.biomedcentral.com/1471-2164/12/458}
}
@ARTICLE{Wang2011x,
author = {Wang, Yu and Chandra, Rashmi and Samsa, Leigh Ann and Gooch, Barry
and Fee, Brian E. and Cook, J. Michael and Vigna, Steven R. and Grant,
Augustus O. and Liddle, Rodger A.},
title = {Amino acids stimulate cholecystokinin release through the Ca2+-sensing
receptor},
journal = {Am J Physiol Gastrointest Liver Physiol},
year = {2011},
volume = {300},
pages = {G528--537},
number = {4},
month = apr,
abstract = {Cholecystokinin (CCK) is produced by discrete endocrine cells in the
proximal small intestine and is released following the ingestion
of food. CCK is the primary hormone responsible for gallbladder contraction
and has potent effects on pancreatic secretion, gastric emptying,
and satiety. In addition to fats, digested proteins and aromatic
amino acids are major stimulants of CCK release. However, the cellular
mechanism by which amino acids affect CCK secretion is unknown. The
Ca2+-sensing receptor (CaSR) that was originally identified on parathyroid
cells is not only sensitive to extracellular Ca2+ but is activated
by extracellular aromatic amino acids. It has been postulated that
this receptor may be involved in gastrointestinal hormone secretion.
Using transgenic mice expressing a CCK promoter driven/enhanced green
fluorescent protein (GFP) transgene, we have been able to identify
and purify viable intestinal CCK cells. Intestinal mucosal CCK cells
were enriched >200-fold by fluorescence-activated cell sorting. These
cells were then used for real-time PCR identification of CaSR. Immunohistochemical
staining with an antibody specific for CaSR confirmed colocalization
of CaSR to CCK cells. In isolated CCK cells loaded with a Ca2+-sensitive
dye, the amino acids phenylalanine and tryptophan, but not nonaromatic
amino acids, caused an increase in intracellular Ca2+ ([Ca2+]i).
The increase in [Ca2+]i was blocked by the CaSR inhibitor Calhex
231. Phenylalanine and tryptophan stimulated CCK release from intestinal
CCK cells, and this stimulation was also blocked by CaSR inhibition.
Electrophysiological recordings from isolated CCK-GFP cells revealed
these cells to possess a predominant outwardly rectifying potassium
current. Administration of phenylalanine inhibited basal K+ channel
activity and caused CCK cell depolarization, consistent with changes
necessary for hormone secretion. These findings indicate that amino
acids have a direct effect on CCK cells to stimulate CCK release
by activating CaSR and suggest that CaSR is the physiological mechanism
through which amino acids regulate CCK secretion.},
comment = {10.1152/ajpgi.00387.2010},
url = {http://ajpgi.physiology.org/cgi/content/abstract/300/4/G528}
}
@ARTICLE{Wang2008l,
author = {Wang, Yanfang and Couture, Oliver and Qu, Long and Uthe, Jolita and
Bearson, Shawn and Kuhar, Daniel and Lunney, Joan and Nettleton,
Dan and Dekkers, Jack and Tuggle, Christopher},
title = {Analysis of Porcine Transcriptional Response to Salmonella enterica
serovar Choleraesuis suggests novel targets of NFkappaB are activated
in the Mesenteric Lymph Node},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {437},
number = {1},
abstract = {BACKGROUND:Specific knowledge of the molecular pathways controlling
host-pathogen interactions can increase our understanding of immune
response biology as well as provide targets for drug development
and genetic improvement of disease resistance. Toward this end, we
have characterized the porcine transcriptional response to Salmonella
enterica serovar Choleraesuis (S. Choleraesuis), a Salmonella serovar
that predominately colonizes swine, yet can cause serious infections
in human patients. Affymetrix technology was used to screen for differentially
expressed genes in pig mesenteric lymph nodes (MLN) responding to
infection with S. Choleraesuis at acute (8 hours (h), 24 h and 48
h post-inoculation (pi)) and chronic stages (21 days (d) pi).RESULTS:Analysis
of variance with false discovery rate control identified 1,853 genes
with significant changes in expression level (p-value < 0.01, q-value
< 0.26, and fold change (FC) > 2) during infection as compared to
un-inoculated control pigs. Down-regulation of translation-related
genes at 8 hpi and 24 hpi implied that S. Choleraesuis repressed
host protein translation. Genes involved in the Th1, innate immune/inflammation
response and apoptosis pathways were induced significantly. However,
antigen presentation/dendritic cell (DC) function pathways were not
affected significantly during infection. A strong NF?B-dependent
response was observed, as 58 known NF?B target genes were induced
at 8, 24 and/or 48 hpi. Quantitative-PCR analyses confirmed the microarray
data for 21 of 22 genes tested. Based on expression patterns, these
target genes can be classified as an "Early" group (induced at either
8 or 24 hpi) and a "Late" group (induced only at 48 hpi). Cytokine
activity or chemokine activity were enriched within the Early group
genes GO annotations, while the Late group was predominantly composed
of signal transduction and cell metabolism annotated genes. Regulatory
motif analysis of the human orthologous promoters for both Early
and Late genes revealed that 241 gene promoters were predicted to
contain NF?B binding sites, and that of these, 51 Early and 145 Late
genes were previously not known to be NF?B targets.CONCLUSION:Our
study provides novel genome-wide transcriptional profiling data on
the porcine response to S. Choleraesuis and expands the understanding
of NF?B signaling in response to Salmonella infection. Comparison
of the magnitude and timing of porcine MLN transcriptional response
to different Salmonella serovars, S. Choleraesuis and S. Typhimurium,
clearly showed a larger but later transcriptional response to S.
Choleraesuis. Both microarray and QPCR data provided evidence of
a strong NF?B-dependent host transcriptional response during S. Choleraesuis
infection. Our data indicate that a lack of strong DC-mediated antigen
presentation in the MLN may cause S. Choleraesuis infected pigs to
develop a systemic infection, and our analysis predicts nearly 200
novel NF?B target genes which may be applicable across mammalian
species.},
doi = {10.1186/1471-2164-9-437},
issn = {1471-2164},
pubmedid = {18811943},
url = {http://www.biomedcentral.com/1471-2164/9/437}
}
@ARTICLE{Wang2006f,
author = {Wang, Yongzhong And Gabrielsen, Anders And Lawler, Patrick R. And
Paulsson-berne, Gabrielle And Steinbrãœchel, Daniel A. And Hansson,
Goran K. And Kastrup, Jens},
title = {Myocardial Gene Expression of Angiogenic Factors in Human Chronic
Ischemic Myocardium: Influence of Acute Ischemia/Cardioplegia and
Reperfusion},
journal = {Microcirculation},
year = {2006},
volume = {13},
pages = {187--197},
number = {3},
abstract = {ABSTRACT Objective: Angiogenic therapies in animals have demonstrated
the development of new blood vessels within ischemic myocardium.
However, results from clinical protein and gene angiogenic trials
have been less impressive. The present study aimed to investigate
the expression of angiogenic genes in human chronic ischemic myocardium
and the influence of acute ischemia/cardioplegia and reperfusion
on their expression. Methods: Myocardial biopsies were taken from
chronic ischemic and nonischemic myocardium in 15 patients with stable
angina pectoris during coronary bypass surgery. Tissue samples were
evaluated by oligonucleotide microarray and quantitative real-time
PCR for the expression of angiogenic factors. Results: There was
identical baseline expression of VEGF-A and VEGF-C mRNA in chronic
ischemic myocardium compared with nonischemic myocardium. Reperfusion
increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic
and ischemic myocardium. VEGF-A protein was detected mainly in the
extracellular matrix around the cardiomyocytes in ischemic myocardium.
Conclusion: These data suggest that the nonconclusive VEGF gene therapy
trials chronic coronary artery disease was not due to a preexisting
upregulation of VEGF in chronic ischemic myocardium. There might
be room for further therapeutic angiogenesis in chronic ischemic
myocardium.},
issn = {1549-8719},
keywords = {angiogenesis, gene expression, growth factors, myocardial ischemia,
reperfusion},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1080/10739680600556811}
}
@ARTICLE{Wang2011q,
author = {Wang, Ying and Ghaffari, Noushin and Johnson, Charles and Braga-Neto,
Ulisses and Wang, Hui and Chen, Rui and Zhou, Huaijun},
title = {Evaluation of the coverage and depth of transcriptome by RNA-Seq
in chickens},
journal = {BMC Bioinformatics},
year = {2011},
volume = {12},
pages = {S5},
number = {Suppl 10},
abstract = {BACKGROUND:RNA-Seq is the recently developed high-throughput sequencing
technology for profiling the entire transcriptome in any organism.
It has several major advantages over current hybridization-based
approach such as microarrays. However, the cost per sample by RNA-Seq
is still prohibitive for most laboratories. With continued improvement
in sequence output, it would be cost-effective if multiple samples
are multiplexed and sequenced in a single lane with sufficient transcriptome
coverage. The objective of this analysis is to evaluate what sequencing
depth might be sufficient to interrogate gene expression profiling
in the chicken by RNA-Seq.RESULTS:Two cDNA libraries from chicken
lungs were sequenced initially, and 4.9 million (M) and 1.6 M (60
bp) reads were generated, respectively. With significant improvements
in sequencing technology, two technical replicate cDNA libraries
were re-sequenced. Totals of 29.6 M and 28.7 M (75 bp) reads were
obtained with the two samples. More than 90% of annotated genes were
detected in the data sets with 28.7-29.6 M reads, while only 68%
of genes were detected in the data set with 1.6 M reads. The correlation
coefficients of gene expression between technical replicates within
the same sample were 0.9458 and 0.8442. To evaluate the appropriate
depth needed for mRNA profiling, a random sampling method was used
to generate different number of reads from each sample. There was
a significant increase in correlation coefficients from a sequencing
depth of 1.6 M to 10 M for all genes except highly abundant genes.
No significant improvement was observed from the depth of 10 M to
20 M (75 bp) reads.CONCLUSION:The analysis from the current study
demonstrated that 30 M (75 bp) reads is sufficient to detect all
annotated genes in chicken lungs. Ten million (75 bp) reads could
detect about 80% of annotated chicken genes, and RNA-Seq at this
depth can serve as a replacement of microarray technology. Furthermore,
the depth of sequencing had a significant impact on measuring gene
expression of low abundant genes. Finally, the combination of experimental
and simulation approaches is a powerful approach to address the relationship
between the depth of sequencing and transcriptome coverage.},
doi = {10.1186/1471-2105-12-S10-S5},
issn = {1471-2105},
pubmedid = {22165852},
url = {http://www.biomedcentral.com/1471-2105/12/S10/S5}
}
@ARTICLE{Wang2012a,
author = {Wang, Ying and Kocher, Sarah D. and Linksvayer, Timothy A. and Grozinger,
Christina M. and Page, Robert E., Jr and Amdam, Gro V.},
title = {Regulation of behaviorally associated gene networks in worker honey
bee ovaries},
journal = {J. Exp. Biol.},
year = {2012},
volume = {215},
pages = {124-134},
number = {1},
abstract = {Several lines of evidence support genetic links between ovary size
and division of labor in worker honey bees. However, it is largely
unknown how ovaries influence behavior. To address this question,
we first performed transcriptional profiling on worker ovaries from
two genotypes that differ in social behavior and ovary size. Then,
we contrasted the differentially expressed ovarian genes with six
sets of available brain transcriptomes. Finally, we probed behavior-related
candidate gene networks in wild-type ovaries of different sizes.
We found differential expression in 2151 ovarian transcripts in these
artificially selected honey bee strains, corresponding to approximately
20.3% of the predicted gene set of honey bees. Differences in gene
expression overlapped significantly with changes in the brain transcriptomes.
Differentially expressed genes were associated with neural signal
transmission (tyramine receptor, TYR) and ecdysteroid signaling;
two independently tested nuclear hormone receptors (HR46 and ftz-f1)
were also significantly correlated with ovary size in wild-type bees.
We suggest that the correspondence between ovary and brain transcriptomes
identified here indicates systemic regulatory networks among hormones
(juvenile hormone and ecdysteroids), pheromones (queen mandibular
pheromone), reproductive organs and nervous tissues in worker honey
bees. Furthermore, robust correlations between ovary size and neuraland
endocrine response genes are consistent with the hypothesized roles
of the ovaries in honey bee behavioral regulation.},
doi = {10.1242/jeb.060889},
eprint = {http://jeb.biologists.org/cgi/reprint/215/1/124.pdf},
url = {http://jeb.biologists.org/cgi/content/abstract/215/1/124}
}
@ARTICLE{Wang2011e,
author = {Wang, Yi and Li, Xiangzhen and Mao, Yuejian and Blaschek, Hans},
title = {Single-nucleotide resolution analysis of the transcriptome structure
of Clostridium beijerinckii NCIMB 8052 using RNA-Seq},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {479},
number = {1},
abstract = {BACKGROUND:Clostridium beijerinckii is an important solvent producing
microorganism. The genome of C. beijerinckii NCIMB 8052 has recently
been sequenced. Although transcriptome structure is important in
order to reveal the functional and regulatory architecture of the
genome, the physical structure of transcriptome for this strain,
such as the operon linkages and transcript boundaries are not well
understood.RESULTS:In this study, we conducted a single-nucleotide
resolution analysis of the C. beijerinckii NCIMB 8052 transcriptome
using high-throughput RNA-Seq technology. We identified the transcription
start sites and operon structure throughout the genome. We confirmed
the structure of important gene operons involved in metabolic pathways
for acid and solvent production in C. beijerinckii 8052, including
pta-ack, ptb-buk, hbd-etfA-etfB-crt (bcs) and ald-ctfA-ctfB-adc (sol)
operons; we also defined important operons related to chemotaxis/motility,
transcriptional regulation, stress response and fatty acids biosynthesis
along with others. We discovered 20 previously non-annotated regions
with significant transcriptional activities and 15 genes whose translation
start codons were likely mis-annotated. As a consequence, the accuracy
of existing genome annotation was significantly enhanced. Furthermore,
we identified 78 putative silent genes and 177 putative housekeeping
genes based on normalized transcription measurement with the sequence
data. We also observed that more than 30% of pseudogenes had significant
transcriptional activities during the fermentation process. Strong
correlations exist between the expression values derived from RNA-Seq
analysis and microarray data or qRT-PCR results.CONCLUSIONS:Transcriptome
structural profiling in this research provided important supplemental
information on the accuracy of genome annotation, and revealed additional
gene functions and regulation in C. beijerinckii.},
doi = {10.1186/1471-2164-12-479},
issn = {1471-2164},
pubmedid = {21962126},
url = {http://www.biomedcentral.com/1471-2164/12/479}
}
@ARTICLE{Wang2004d,
author = {Wang, Yan and Middleton, Frank and Horton, Jason A. and Reichel,
Lee and Farnum, Cornelia E. and Damron, Timothy A.},
title = {Microarray analysis of proliferative and hypertrophic growth plate
zones identifies differentiation markers and signal pathways},
journal = {Bone},
year = {2004},
volume = {35},
pages = {1273--1293},
number = {6},
month = dec,
abstract = {Longitudinal bone growth results from coordination of proliferation
and hypertrophy of chondrocytes, calcification of the matrix, vascular
invasion, and completion of endochondral bone formation in the growth
plate. Although proliferative and hypertrophic chondrocytes are well
characterized histomorphologically, the understanding of factors
governing this transition is not fully explained. Our hypothesis
was that significant differential gene expression exists between
proliferative and hypertrophic chondrocytes that may provide clues
to the regulation of this transition at the transcriptional level.
Normal Sprague-Dawley rat growth plate chondrocytes from the proliferative
zone (PZ) and hypertrophic zone (HZ) were isolated by laser capture
microdissection and then subjected to microarray analysis. Confirmation
of the differential expression of selected genes was done by in situ
hybridization and quantitative reverse transcription (RT) polymerase
chain reaction (PCR). A total of 40 transcripts showed at least twofold
fgreater expression in the PZ compared to HZ at both 6 and 7 weeks
of age, while 52 transcripts showed twofold greater expression in
the HZ compared to PZ at these time points. Many of the differentially
expressed genes in each zone had very high levels of expression and
thus were classified as "enriched transcripts" for that zone. The
PZ-enriched transcripts included fibromodulin, proline arginine-rich
end leucine-rich repeat protein, lactate dehydrogenase, and enolase
1 alpha. In contrast, HZ-enriched transcripts included collagen I,
protein kinase (lysine deficient 4), proteasome (prosome, macropain)
activator subunit 4, prostaglandin I2 synthase, and integrin-binding
sialoprotein, matrix metalloproteinase 13 (MMP13), and collagen X.
Other genes were highly expressed in cells from both zones, including
collagen II, aggrecan, cartilage oligomeric protein, cartilage link
protein, laminin receptor, and eukaryotic translocation elongation
factor. Functional classification of the PZ-enriched transcripts
showed an increased percentage of genes expressed in nuclear cell
cycle and transcription functions. In contrast, the HZ-enriched transcripts
were more involved in extracellular structure and membrane receptor
and transporter functions. Pathway analysis indicated that transforming
growth factor [beta] and parathyroid hormone-related protein (PTHrP)
pathways were important in both zones, and bone morphogenic protein
pathway played a role in the HZ. It is likely that these differentially
expressed genes are involved in regulation of the transition from
proliferation to differentiation functions in the growth plate.},
issn = {8756-3282},
keywords = {Growth plate, Microarray, Chondrocytes, Rat, Bone},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4DS8F3V-1/2/658069f7e4190cd7deef0e32333fa342}
}
@ARTICLE{Wang2011y,
author = {Wang, Yong and Morimoto, Sho and Ogawa, Naoto and Fujii, Takeshi},
title = {A survey of the cellular responses in Pseudomonas putida KT2440 growing
in sterilized soil by microarray analysis},
journal = {FEMS Microbiology Ecology},
year = {2011},
volume = {78},
pages = {220--232},
number = {2},
abstract = {Genome-wide scanning of gene expression by microarray techniques was
successfully performed on RNA extracted from sterilized soil inoculated
with Pseudomonas putida KT2440/pSL1, which contains a chloroaromatic
degrading plasmid, in the presence or absence of 3-chlorobenzoic
acid (3CB). The genes showing significant changes in their expression
in both the triplicate-microarray analysis using amplified RNA and
the single-microarray analysis using unamplified RNA were investigated.
Pathway analysis revealed that the benzoate degradation pathway underwent
the most significant changes following treatment with 3CB. Analysis
based on categorization of differentially expressed genes against
3CB revealed new findings about the cellular responses of the bacteria
to 3CB. Genes specifically involved in the transport of 3CB were
upregulated, including a K+/H+ antiporter complex, a universal stress
protein, two cytochrome P450 proteins and an efflux transporter.
The downregulated expression of several genes involved in carbon
metabolism and the genes belonging to a prophage in the presence
of 3CB was observed. This study demonstrated the applicability of
the method of soil RNA extraction for microarray analysis of gene
expression in bacteria growing in sterilized soil.},
doi = {10.1111/j.1574-6941.2011.01146.x},
issn = {1574-6941},
keywords = {gene expression, RNA extraction, quantitative RT-PCR, mRNA amplification},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6941.2011.01146.x}
}
@ARTICLE{Wang2011a,
author = {Wang, Yan and Peng, Xiaoli and Xu, Wentao and Luo, YunBo and Zhao,
Weiwei and Hao, Junran and Liang, Zhihong and Zhang, Yu and Huang,
Kunlun},
title = {Transcript and protein profiling analysis of OTA-induced cell death
reveals the regulation of the toxicity response process in Arabidopsis
thaliana},
journal = {J. Exp. Bot.},
year = {2011},
pages = {err447},
abstract = {Ochratoxin A (OTA) is a toxic isocoumarin derivative produced by various
species of mould which mainly grow on grain, coffee, and nuts. Recent
studies have suggested that OTA induces cell death in plants. To
investigate possible mechanisms of OTA phytotoxicity, both digital
gene expression (DGE) transcriptomic and two-dimensional electrophoresis
proteomic analyses were used, through which 3118 genes and 23 proteins
were identified as being up- or down-regulated at least 2-fold in
Arabidopsis leaf in response to OTA treatment. First, exposure of
excised Arabidopsis thaliana leaves to OTA rapidly causes the hypersensitive
reponse, significantly accelerates the increase of reactive oxygen
species and malondialdehyde, and enhances antioxidant enzyme defence
responses and xenobiotic detoxification. Secondly, OTA stimulation
causes dynamic changes in transcription factors and activates the
membrane transport system dramatically. Thirdly, a concomitant persistence
of compromised photosynthesis and photorespiration is indicative
of a metabolic shift from a highly active to a weak state. Finally,
the data revealed that ethylene, salicylic acid, jasmonic acid, and
mitogen-activated protein kinase signalling molecules mediate the
process of toxicity caused by OTA. Profiling analyses on Arabidopsis
in response to OTA will provide new insights into signalling transduction
that modulates the OTA phytotoxicity mechanism, facilitate mapping
of regulatory networks, and extend the ability to improve OTA tolerance
in Arabidopsis.},
doi = {10.1093/jxb/err447},
eprint = {http://jxb.oxfordjournals.org/cgi/reprint/err447v1.pdf},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/err447v1}
}
@ARTICLE{Wang2007h,
author = {Wang, Yanfang and Qu, Long and Uthe, Jolita J. and Bearson, Shawn
M.D. and Kuhar, Daniel and Lunney, Joan K. and Couture, Oliver P.
and Nettleton, Dan and Dekkers, Jack C.M. and Tuggle, Christopher
K.},
title = {Global transcriptional response of porcine mesenteric lymph nodes
to Salmonella enterica serovar Typhimurium},
journal = {Genomics},
year = {2007},
volume = {90},
pages = {72--84},
number = {1},
month = jul,
abstract = {To elucidate the host transcriptional response to Salmonella enterica
serovar Typhimurium, Affymetrix porcine GeneChip analysis of pig
mesenteric lymph nodes was used to identify 848 genes showing differential
expression across different times after inoculation or when compared
to non-inoculated controls. Annotation analyses showed that a high
proportion of these differentially expressed (DE) genes are involved
in immune and inflammatory responses. T helper 1, innate/inflammatory,
and antigen-processing pathways were induced at 24 h post-inoculation
(hpi) and/or 48 hpi, while apoptosis and antigen presentation/dendritic
cell function pathways were downregulated at 8 hpi. Cluster analyses
revealed that most DE genes annotated as NF[kappa]B targets were
grouped into a specific induced subcluster, while many translation-related
DE genes were found in a repressed subcluster. Quantitative polymerase
chain reaction analyses confirmed the Affymetrix results, revealing
transcriptional induction of NF[kappa]B target genes at 24 hpi and
suppression of the NF[kappa]B pathway from 24 to 48 hpi. We propose
that such NF[kappa]B suppression in antigen-presenting cells may
be the mechanism by which S. Typhimurium eludes a strong inflammatory
response to establish a carrier status in pigs.},
issn = {0888-7543},
keywords = {Porcine, Gene expression, Salmonella typhimurium, Immune response,
NF[kappa]B},
url = {http://www.sciencedirect.com/science/article/B6WG1-4NRVTS2-1/2/f14665cf8b45e6e37bd77839224055ae}
}
@ARTICLE{Wang2009r,
author = {Wang, Yanfang and Rathinam, Rajamani and Walch, Amelia and Alahari,
Suresh K.},
title = {ST14 (Suppression of Tumorigenicity 14) Gene Is a Target for miR-27b,
and the Inhibitory Effect of ST14 on Cell Growth Is Independent of
miR-27b Regulation},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {23094--23106},
number = {34},
month = aug,
abstract = {MicroRNAs are noncoding, endogenous small RNAs that regulate target
genes by cleavage of the targeted mRNA or translational repression.
We investigated the microRNAome using 2-color microarrays in a highly
invasive human breast cancer cell line, MDA-MB-231 (subline 4175)
and a noninvasive breast epithelial cell line, MCF10A. We found 13
microRNAs that were up-regulated, and nine were down-regulated significantly
in 4175 cells (p < 0.05, -fold change >2) compared with MCF10A cells.
Interestingly, miR-27b and its putative target gene, ST14 (suppressor
of tumorigenicity 14), had inverse expression pattern in breast cancer
cells. The 3'-untranslated region of ST14 contains a regulatory element
for miR-27b, and our luciferase experiments indicate that antisense
miR-27b enhances ST14 expression in cancer cells. Furthermore, antagomir
of miR-27b suppressed cell invasion in 4175 cells, whereas pre-miR-27b
stimulated invasion in moderately invasive ZR75 breast cancer cells.
In addition, ST14 reduces cell proliferation as well as cell migration
and invasion. Analysis of human breast tumors revealed that miR-27b
expression increases during cancer progression, paralleling a decrease
in ST14 expression. Furthermore, our data indicate that ST14 inhibits
cells from entering into S phase by up-regulating p27, which results
in down-regulation of cyclin E-CDK2 complexes, suggesting ST14 reduces
cell growth through its effects on cell cycle-related proteins. Introduction
of miR-27b into ST14-expressing cells did not suppress the effect
on cell growth. These findings suggest that ST14 plays an important
role in several biological processes, and some effects are not completely
dependent on miR-27b regulation.},
url = {http://www.jbc.org/cgi/content/abstract/284/34/23094}
}
@ARTICLE{Wang2006g,
author = {Wang, Yun and Seburn, Kevin and Bechtel, Lawrence and Lee, Bruce
Y. and Szatkiewicz, Jin P. and Nishina, Patsy M. and Naggert, Jurgen
K.},
title = {Defective carbohydrate metabolism in mice homozygous for the tubby
mutation},
journal = {Physiol Genomics},
year = {2006},
volume = {27},
pages = {131--140},
number = {2},
month = oct,
abstract = {Tub is a member of a small gene family, the tubby-like proteins (TULPs),
with predominant expression in neurons. Mice carrying a mutation
in Tub develop retinal and cochlear degeneration as well as late-onset
obesity with insulin resistance. During behavioral and metabolic
testing, we found that homozygous C57BL/6J-Tubtub mice have a lower
respiratory quotient than C57BL/6J controls before the onset of obesity,
indicating that tubby homozygotes fail to activate carbohydrate metabolism
and instead rely on fat metabolism for energy needs. In concordance
with this, tubby mice show higher excretion of ketone bodies and
accumulation of glycogen in the liver. Quantitation of liver mRNA
levels shows that, during the transition from light to dark period,
tubby mice fail to induce glucose-6-phosphate dehydrogenase (G6pdh),
the rate-limiting enzyme in the pentose phosphate pathway that normally
supplies NADPH for de novo fatty acid synthesis and glutathione reduction.
Reduced G6PDH protein levels and enzymatic activity in tubby mice
lead accordingly to lower levels of NADPH and reduced glutathione
(GSH), respectively. mRNA levels for the lipolytic enzymes acetyl-CoA
synthetase and carnitine palmitoyltransferase are increased during
the dark cycle and decreased during the light period, and several
citric acid cycle genes are dysregulated in tubby mice. Examination
of hypothalamic gene expression showed high levels of preproorexin
mRNA leading to accumulation of orexin peptide in the lateral hypothalamus.
We hypothesize that abnormal hypothalamic orexin expression leads
to changes in liver carbohydrate metabolism and may contribute to
the moderate obesity observed in tubby mice.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/27/2/131}
}
@ARTICLE{Wang2011l,
author = {Wang, Yanfang and Shenouda, Sylvia and Baranwal, Somesh and Rathinam,
Rajamani and Jain, Prachi and Bao, Lili and Hazari, Siddhartha and
Dash, Srikanta and Alahari, Suresh},
title = {Integrin subunits alpha5 and alpha6 regulate cell cycle by modulating
the chk1 and Rb/E2F pathways to affect breast cancer metastasis},
journal = {Molecular Cancer},
year = {2011},
volume = {10},
pages = {84},
number = {1},
abstract = {BACKGROUND:Although integrins have been implicated in the progression
of breast cancer, the exact mechanism whereby they exert this regulation
is clearly not understood. To understand the role of integrins in
breast cancer, we examined the expression levels of several integrins
in mouse breast cancer cell lines by flow cytometry and the data
were validated by Western and RT-PCR analysis. The importance of
integrins in cell migration and cell invasion was examined by in
vitro assays. Further the effect of integrins on metastasis was investigated
by in vivo experimental metastasis assays using mouse models.RESULTS:Integrin
alpha5 subunit is highly expressed in the nonmetastatic cell line
67NR and is significantly low in the highly invasive cell line 4T1.
In contrast, expression levels of integrin alpha6 subunit are high
in 4T1 cells and low in 67NR cells. In vitro data indicated that
overexpression of alpha5 subunit and knockdown of alpha6 integrin
subunit inhibited cell proliferation, migration, and invasion. Our
in vivo findings indicated that overexpression of integrin alpha5
subunit and knockdown of alpha6 subunit decreased the pulmonary metastasis
property of 4T1 cells. Our data also indicated that overexpression
of alpha 5 integrin subunit and suppression of alpha6 integrin subunit
inhibited cells entering into S phase by up-regulating p27, which
results in downregulation of cyclinE/CDK2 complexes, This suggests
that these integrins regulate cell growth through their effects on
cell-cycle-regulated proteins. We also found that modulation of these
integrins upregulates E2F, which may induce the expression of chk1
to regulate cdc25A/cyclin E/CDK2/Rb in a feedback loop mechanism.CONCLUSION:This
study indicates that Integrin alpha5 subunit functions as a potential
metastasis suppressor, while alpha6 subunit functions as a metastasis
promoter. The modulation of integrins reduces cdc25 A, another possible
mechanism for downregulation of CDK2. Taken together we demonstrate
a link between integrins and the chk1-cdc25-cyclin E/CDK2-Rb pathway.},
doi = {10.1186/1476-4598-10-84},
issn = {1476-4598},
pubmedid = {21752283},
url = {http://www.molecular-cancer.com/content/10/1/84}
}
@ARTICLE{Wang2010x,
author = {Wang, Yuying and Stary, Joel M. and Wilhelm, James E. and Newmark,
Phillip A.},
title = {A functional genomic screen in planarians identifies novel regulators
of germ cell development},
journal = {Genes \& Dev.},
year = {2010},
volume = {24},
pages = {2081--2092},
number = {18},
month = sep,
abstract = {Germ cells serve as intriguing examples of differentiated cells that
retain the capacity to generate all cell types of an organism. Here
we used functional genomic approaches in planarians to identify genes
required for proper germ cell development. We conducted microarray
analyses and in situ hybridization to discover and validate germ
cell-enriched transcripts, and then used RNAi to screen for genes
required for discrete stages of germ cell development. The majority
of genes we identified encode conserved RNA-binding proteins, several
of which have not been implicated previously in germ cell development.
We also show that a germ cell-specific subunit of the conserved transcription
factor CCAAT-binding protein/nuclear factor-Y is required for maintaining
spermatogonial stem cells. Our results demonstrate that conserved
transcriptional and post-transcriptional mechanisms regulate germ
cell development in planarians. These findings suggest that studies
of planarians will inform our understanding of germ cell biology
in higher organisms.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/24/18/2081}
}
@ARTICLE{Wang2009s,
author = {Wang, Ying and Tilley, Michael and Bean, Scott and Sun, X. Susan
and Wang, Donghai},
title = {Comparison of Methods for Extracting Kafirin Proteins from Sorghum
Distillers Dried Grains with Solubles},
journal = {Journal of Agricultural and Food Chemistry},
year = {2009},
volume = {57},
pages = {8366-8372},
number = {18},
note = {PMID: 19754169},
doi = {10.1021/jf901713w},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf901713w},
url = {http://pubs.acs.org/doi/abs/10.1021/jf901713w}
}
@ARTICLE{Wang2006h,
author = {Wang, Yaming and Zhu, Wei and Levy, David E.},
title = {Nuclear and cytoplasmic mRNA quantification by SYBR green based real-time
RT-PCR},
journal = {Methods},
year = {2006},
volume = {39},
pages = {356--362},
number = {4},
month = aug,
abstract = {Measurement of the steady-state abundance of nuclear and cytoplasmic
RNA requires efficient subcellular fractionation and RNA recovery
coupled with accurate quantification of individual RNA species. Detergent
lysis of tissue culture cells provides a simple fractionation procedure
that can be optimized to individual cell lines. The large dynamic
range, extreme sensitivity, high sequence-specificity, and fast turn-around
time has allowed real-time reverse transcription polymerase chain
reaction (real-time RT-PCR) to become a standard tool for mRNA quantification.
Among the different chemistries used for PCR product detection during
amplification, DNA binding dyes such as SYBR® Green I are simple,
versatile, and yet highly reliable and least expensive. With attention
to primer design and cycling conditions, virtually any mRNA species
can be accurately quantified from even minute quantities of starting
RNA. This method provides an accurate and efficient procedure for
estimating the relative ratios of nuclear and cytoplasmic RNA concentrations.},
booktitle = {Nuclearcytoplasmic Transport and Nuclear Pore Complexes},
issn = {1046-2023},
keywords = {Quantitative real-time PCR, mRNA export, Cell fractionation, Geometric
normalization, Detergent lysis},
url = {http://www.sciencedirect.com/science/article/B6WN5-4KWT4V0-B/2/2360aa36d738b500afdb0e18fb73bb00}
}
@ARTICLE{Wang2010v,
author = {Wang, Y. K. and Zhu, Y. L. and Qiu, F. M. and Zhang, T. and Chen,
Z. G. and Zheng, S. and Huang, J.},
title = {Activation of Akt and MAPK pathways enhances the tumorigenicity of
CD133+ primary colon cancer cells},
journal = {Carcinogenesis},
year = {2010},
volume = {31},
pages = {1376--1380},
number = {8},
month = aug,
abstract = {Cancer stem cells (CSCs) play an important role in carcinogenesis,
resistance to treatment and may lead to cancer recurrence and metastasis.
However, the molecular mechanism of CSC involved in these events
needs to be further elucidated. In this study, CD133+ colon cancer
cells were cultured, which showed CSC properties both in vitro and
in vivo from metastatic tissue. Upstream molecules in Akt and mitogen-activated
protein kinase (MAPK) pathways were preferentially expressed in these
CD133+ cells, as revealed by a global gene chip. The kinase activities
of Akt and extracellular signal-regulated kinase (Erk)1/2 were also
significantly upregulated in CD133+ cells. In addition, the clonogenic
growth of CD133+ cell was reduced greatly by inhibiting the activity
of Akt and Erk1/2. The results revealed the Akt and MAPK pathways
were involved in the tumorigenesis of CD133+ colon cancer cells,
suggesting that molecules in these two pathways might be potential
targets in the future therapy.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/31/8/1376}
}
@ARTICLE{Wang2009t,
author = {Wang, Y.-Q. and Puntenney, S. B. and Burton, J. L. and Forsberg,
N. E.},
title = {Use of gene profiling to evaluate the effects of a feed additive
on immune function in periparturient dairy cattle},
journal = {Journal of Animal Physiology and Animal Nutrition},
year = {2009},
volume = {93},
pages = {66--75},
number = {1},
abstract = {Summary Objectives were to investigate mechanisms by which a nutritional
supplement alters immunity in dairy cattle. Our hypothesis was that
feeding this product to dairy cattle altered neutrophil gene expression.
Eight periparturient Jersey cattle were randomly assigned to one
of two treatments: control and treated. Control animals were fed
a dry cow ration for 1Â month prior to calving. The treated cows
were fed the same ration supplemented with OmniGen-AF. Following
calving, blood samples were taken and neutrophils were prepared after
which RNA was extracted. Gene expression in neutrophils of treated
versus control-fed animals was then assessed using bovine-total leukocyte
(BOTL-5) arrays. Eighteen genes were differentially regulated in
the experimental group and of these, twice as many were up-regulated
as down-regulated. Patterns of changes indicated that the additive
might alter neutrophil apoptosis, signaling and sensitivity. Two
of the regulated genes [interleukin-1β converting enzyme (ICE) and
interleukin-4 receptor (IL-4R)] were investigated in more detail
using quantitative reverse transcriptase-polymerase chain reaction
(QRT-PCR). Each was found to be elevated by the feeding of experimental
product. Increased expression of ICE indicates potential for enhanced
neutrophil expression of interleukin-1β (IL-1β), a cytokine which
plays roles in the inflammatory response and which stimulates adaptive
immunity following innate immune activation. Altered expression of
IL-4R indicates potential for changes in neutrophil apoptosis. The
experiment identified mechanisms by which the additive altered neutrophil
gene expression. While many nutrients support the immune system,
we have shown that a non-traditional nutritional approach may also
have utility in modulating immune function.},
issn = {1439-0396},
keywords = {immunity, neutrophil, dairy, gene profiling, microarray, OmniGen-AF},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0396.2007.00780.x}
}
@ARTICLE{Wang2010w,
author = {Wang, Yi-Ting and Pan, Yu-Jiao and Cho, Chao-Cheng and Lin, Bo-Chi
and Su, Li-Hsin and Huang, Yu-Chang and Sun, Chin-Hung},
title = {A Novel Pax-like Protein Involved in Transcriptional Activation of
Cyst Wall Protein Genes in Giardia lamblia},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {32213--32226},
number = {42},
month = oct,
abstract = {Giardia lamblia differentiates into infectious cysts to survive outside
of the host. It is of interest to identify factors involved in up-regulation
of cyst wall proteins (CWPs) during this differentiation. Pax proteins
are important regulators of development and cell differentiation
in Drosophila and vertebrates. No member of this gene family has
been reported to date in yeast, plants, or protozoan parasites. We
have identified a pax-like gene (pax1) encoding a putative paired
domain in the G. lamblia genome. Epitope-tagged Pax1 localized to
nuclei during both vegetative growth and encystation. Recombinant
Pax1 specifically bound to the AT-rich initiator elements of the
encystation-induced cwp1 to -3 and myb2 genes. Interestingly, overexpression
of Pax1 increased cwp1 to -3 and myb2 gene expression and cyst formation.
Deletion of the C-terminal paired domain or mutation of the basic
amino acids of the paired domain resulted in a decrease of the transactivation
function of Pax1. Our results indicate that the Pax family has been
conserved during evolution, and Pax1 could up-regulate the key encystation-induced
genes to regulate differentiation of the protozoan eukaryote, G.
lamblia.},
url = {http://www.jbc.org/cgi/content/abstract/285/42/32213}
}
@ARTICLE{Wang2010y,
author = {Wang, Zhangying and Fang, Boping and Chen, Jingyi and Zhang, Xiongjian
and Luo, Zhongxia and Huang, Lifei and Chen, Xinliang and Li, Yujun},
title = { De novo assembly and characterization of root transcriptome using
Illumina paired-end sequencing and development of cSSR markers in
sweetpotato (Ipomoea batatas)},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {726},
number = {1},
abstract = {BACKGROUND:The tuberous root of sweetpotato is an important agricultural
and biological organ. There are not sufficient transcriptomic and
genomic data in public databases for understanding of the molecular
mechanism underlying the tuberous root formation and development.
Thus, high throughput transcriptome sequencing is needed to generate
enormous transcript sequences from sweetpotato root for gene discovery
and molecular marker development.RESULTS:In this study, more than
59 million sequencing reads were generated using Illumina paired-end
sequencing technology. De novo assembly yielded 56,516 unigenes with
an average length of 581 bp. Based on sequence similarity search
with known proteins, a total of 35,051 (62.02%) genes were identified.
Out of these annotated unigenes, 5,046 and 11,983 unigenes were assigned
to gene ontology and clusters of orthologous group, respectively.
Searching against the Kyoto Encyclopedia of Genes and Genomes Pathway
database (KEGG) indicated that 17,598 (31.14%) unigenes were mapped
to 124 KEGG pathways, and 11,056 were assigned to metabolic pathways,
which were well represented by carbohydrate metabolism and biosynthesis
of secondary metabolite. In addition, 4,114 cDNA SSRs (cSSRs) were
identified as potential molecular markers in our unigenes. One hundred
pairs of PCR primers were designed and used for validation of the
amplification and assessment of the polymorphism in genomic DNA pools.
The result revealed that 92 primer pairs were successfully amplified
in initial screening tests.CONCLUSION:This study generated a substantial
fraction of sweetpotato transcript sequences, which can be used to
discover novel genes associated with tuberous root formation and
development and will also make it possible to construct high density
microarrays for further characterization of gene expression profiles
during these processes. Thousands of cSSR markers identified in the
present study can enrich molecular markers and will facilitate marker-assisted
selection in sweetpotato breeding. Overall, these sequences and markers
will provide valuable resources for the sweetpotato community. Additionally,
these results also suggested that transcriptome analysis based on
Illumina paired-end sequencing is a powerful tool for gene discovery
and molecular marker development for non-model species, especially
those with large and complex genome.},
doi = {10.1186/1471-2164-11-726},
issn = {1471-2164},
pubmedid = {21182800},
url = {http://www.biomedcentral.com/1471-2164/11/726}
}
@ARTICLE{Wang2011p,
author = {Zhong Wang and Zhi-Wei Jing and Cai-Xiu Zhou and Liang Zhang and
Jing Cheng and Zhan-Jun Zhang and Jun Liu and Cun-Shuan Xu and Peng-Tao
Li and Yong-Yan Wang},
title = {Fusion of core pathways reveals a horizontal synergistic mechanism
underlying combination therapy},
journal = {European Journal of Pharmacology},
year = {2011},
volume = {667},
pages = {278 - 286},
number = {1–3},
abstract = {Combination therapies have recently been shown to be more effective
than monotherapies that may provide synergistic effects in the treatment
of stroke, but its selective mechanism still remains unclear. Based
on the median-effect method, the combination therapy of jasminoidin
and ursodeoxycholic acid had a synergic effect on reducing the infarct
volume. The numbers of up- or down-regulated genes by at least 1.5-fold
in the vehicle, jasminoidin, ursodeoxycholic acid, and the combination
of jasminoidin and ursodeoxycholic acid treatment groups were 228,
95, 136, and 101, respectively. According to clustering and principal
component analysis, the pattern of gene expression in the combination
group was similar to that of jasminoidin group rather than ursodeoxycholic
acid group. Based on these nine top sequences in the combination
group excluding four overlapping pathways (MAPK-ERK, Kitlg, Icam1-Ap1,
and prolactin), the jasminoidin group had four (PRLR-STAT1, AcvR2-AcvR1B,
ACVR1/2A-SMAD1, GHR-NF-κB) contributing pathways, and the ursodeoxycholic
acid group had one (IL-6) contributing pathway. Based on the multiple-pathway-dependent
comparison analysis (MPDCA), it may lead to the conclusion that jasminoidin
possibly contributes more important pharmacological effect in the
combined treatment as jasminoidin regulated 80% of the pathways that
the combination group mediated. The study reveals a horizontal synergistic
effect by optimizing the fusion of more pathways from the compounds
with more contribution to the combination therapy. Rather than selecting
compounds only based on experience in the past, this study would
give a new insight into the systematic strategies for designing synergistic
combination therapies.},
doi = {10.1016/j.ejphar.2011.05.046},
issn = {0014-2999},
keywords = {Multiple-pathway-dependent comparison analysis},
url = {http://www.sciencedirect.com/science/article/pii/S0014299911006297}
}
@ARTICLE{Wang2011o,
author = {Wang, Zhang and Kadouri, Daniel and Wu, Martin},
title = {Genomic insights into an obligate epibiotic bacterial predator: Micavibrio
aeruginosavorus ARL-13},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {453},
number = {1},
abstract = {BACKGROUND:Although bacterial predators play important roles in the
dynamics of natural microbial communities, little is known about
the molecular mechanism of bacterial predation and the evolution
of diverse predatory lifestyles.RESULTS:We determined the complete
genome sequence of Micavibrio aeruginosavorus ARL-13, an obligate
bacterial predator that feeds by "leeching" externally to its prey.
Despite being an obligate predator depending on prey for replication,
M. aeruginosavorus encodes almost all major metabolic pathways. However,
our genome analysis suggests that there are multiple amino acids
that it can neither make nor import directly from the environment,
thus providing a simple explanation for its strict dependence on
prey. Remarkably, despite apparent genome reduction, there is a massive
expansion of genomic islands of foreign origin. At least nine genomic
islands encode many genes that are likely important for Micavibrio-prey
interaction such as hemolysin-related proteins. RNA-Seq analysis
shows substantial transcriptome differences between the attack phase,
when M. aeruginosavorus seeks its prey, and the attachment phase,
when it feeds and multiplies. Housekeeping genes as well as genes
involved in protein secretion were all dramatically up-regulated
in the attachment phase. In contrast, genes involved in chemotaxis
and flagellum biosynthesis were highly expressed in the attack phase
but were shut down in the attachment phase. Our transcriptomic analysis
identified additional genes likely important in Micavibrio predation,
including porins, pilins and many hypothetical genes.CONCLUSIONS:The
findings from our phylogenomic and transcriptomic analyses shed new
light on the biology and evolution of the epibiotic predatory lifestyle
of M. aeruginosavorus. The analysis reported here and the availability
of the complete genome sequence should catalyze future studies of
this organism.},
doi = {10.1186/1471-2164-12-453},
issn = {1471-2164},
pubmedid = {21936919},
url = {http://www.biomedcentral.com/1471-2164/12/453}
}
@ARTICLE{Wang2006i,
author = {Wang, Zhenyu and Sekulovic, Andrea and Kutter, Jörg P. and Bang,
Dang D. and Wolff, Anders},
title = {Towards a portable microchip system with integrated thermal control
and polymer waveguides for real-time PCR},
journal = {ELECTROPHORESIS},
year = {2006},
volume = {27},
pages = {5051--5058},
number = {24},
abstract = {Abstract 10.1002/elps.200600355.abs A novel real-time PCR microchip
platform with integrated thermal system and polymer waveguides has
been developed. The integrated polymer optical system for real-time
monitoring of PCR was fabricated in the same SU-8 layer as the PCR
chamber, without additional masking steps. Two suitable DNA binding
dyes, SYTOX Orange and TO-PRO-3, were selected and tested for the
real-time PCR processes. As a model, cadF gene of Campylobacter jejuni
has been amplified on the microchip. Using the integrated optical
system of the real-time PCR microchip, the measured cycle threshold
values of the real-time PCR performed with a dilution series of C. jejuni
DNA template (2 to 200 pg/µL) could be quantitatively detected
and compared with a conventional post-PCR analysis (DNA gel electrophoresis).
The presented approach provided reliable real-time quantitative information
of the PCR amplification of the targeted gene. With the integrated
optical system, the reaction dynamics at any location inside the
micro reaction chamber can easily be monitored.},
issn = {1522-2683},
keywords = {Integrated thermal system, Polymer waveguides, Real-time PCR, SU-8},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200600355}
}
@ARTICLE{Wang2011ac,
author = {Wang, Zheng-Ming and Xue, Wei and Dong, Chun-Juan and Jin, Long-Guo
and Bian, Shao-Min and Wang, Chuan and Wu, Xiu-Yun and Liu, Jin-Yuan},
title = {A Comparative miRNAome Analysis Reveals Seven Fiber Initiation-Related
and 36 Novel miRNAs in Developing Cotton Ovules},
journal = {Mol Plant},
year = {2011},
pages = {ssr094},
abstract = {An increasing number of microRNAs (miRNAs) have been shown to play
crucial regulatory roles in the process of plant development. Here,
we used high-throughput sequencing combined with computational analysis
to characterize miRNAomes from the ovules of wild-type upland cotton
and a fiberless mutant during fiber initiation. Comparative miRNAome
analysis combined with northern blotting and RACE-PCR revealed seven
fiber initiation-related miRNAs expressed in cotton ovules and experimentally
validated targets of these miRNAs are involved in different cellular
responses and metabolic processes, including transcriptional regulation,
auxin and gibberellin signal transduction, actin bundles, and lignin
biosynthesis. This paper describes a complex regulatory network consisting
of these miRNAs expressed in cotton ovules to coordinate fiber initiation
responses. In addition, 36 novel miRNAs and two conserved miRNAs
were newly identified, nearly doubling the number of known cotton
miRNA families to a total of 78. Furthermore, a chromatin remodeling
complex subunit and a pre-mRNA splicing factor are shown for the
first time to be miRNA targets. To our knowledge, this study is the
first systematic investigation of fiber initiation-related miRNAs
and their targets in the developing cotton ovule, deepening our understanding
of the important regulatory functions of miRNAs in cotton fiber initiation.},
doi = {10.1093/mp/ssr094},
eprint = {http://mplant.oxfordjournals.org/cgi/reprint/ssr094v1.pdf},
url = {http://mplant.oxfordjournals.org/cgi/content/abstract/ssr094v1}
}
@ARTICLE{Wangemann2009,
author = {Wangemann, Philine and Kim, Hyoung-Mi and Billings, Sara and Nakaya,
Kazuhiro and Li, Xiangming and Singh, Ruchira and Sharlin, David
S. and Forrest, Douglas and Marcus, Daniel C. and Fong, Peying},
title = {Developmental delays consistent with cochlear hypothyroidism contribute
to failure to develop hearing in mice lacking Slc26a4/pendrin expression},
journal = {Am J Physiol Renal Physiol},
year = {2009},
volume = {297},
pages = {F1435--1447},
number = {5},
month = nov,
abstract = {Mutations of SLC26A4 cause an enlarged vestibular aqueduct, nonsyndromic
deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes
pendrin, an anion exchanger located in the cochlea, thyroid, and
kidney. The goal of the present study was to determine whether developmental
delays, possibly mediated by systemic or local hypothyroidism, contribute
to the failure to develop hearing in mice lacking Slc26a4 (Slc26a4-/-).
We evaluated thyroid function by voltage and pH measurements, by
array-assisted gene expression analysis, and by determination of
plasma thyroxine levels. Cochlear development was evaluated for signs
of hypothyroidism by microscopy, in situ hybridization, and quantitative
RT-PCR. No differences in plasma thyroxine levels were found in Slc26a4-/-
and sex-matched Slc26a4+/- littermates between postnatal day 5 (P5)
and P90. In adult Slc26a4-/- mice, the transepithelial potential
and the pH of thyroid follicles were reduced. No differences in the
expression of genes that participate in thyroid hormone synthesis
or ion transport were observed at P15, when plasma thyroxine levels
peaked. Scala media of the cochlea was 10-fold enlarged, bulging
into and thereby displacing fibrocytes, which express Dio2 to generate
a cochlear thyroid hormone peak at P7. Cochlear development, including
tunnel opening, arrival of efferent innervation at outer hair cells,
endochondral and intramembraneous ossification, and developmental
changes in the expression of Dio2, Dio3, and Tectb were delayed by
1-4 days. These data suggest that pendrin functions as a HCO3- transporter
in the thyroid, that Slc26a4-/- mice are systemically euthyroid,
and that delays in cochlear development, possibly due to local hypothyroidism,
lead to the failure to develop hearing.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/297/5/F1435}
}
@ARTICLE{Wannenes2008,
author = {Wannenes, Francesca and Caprio, Massimiliano and Gatta, Lucia and
Fabbri, Andrea and Bonini, Sergio and Moretti, Costanzo},
title = {Androgen receptor expression during C2C12 skeletal muscle cell line
differentiation},
journal = {Molecular and Cellular Endocrinology},
year = {2008},
volume = {292},
pages = {11--19},
number = {1-2},
month = sep,
abstract = {The Androgen Receptor (AR) pathway is involved in the development
of skeletal muscle but the molecular basis of androgen-related myogenic
enhancement is still unclear. We have investigated AR expression
and localization during myoblasts-myotubes differentiation in skeletal
muscle cell line C2C12. AR expression increases during proliferation
and commitment phase and its levels remain elevated in myotubes.
In proliferating and committed cells in the absence of testosterone,
AR protein localizes in the nuclei whereas it is almost totally localized
in the cytoplasm in myotubes. Low testosterone doses shift the receptor
in the nuclei without increasing the amount of total protein. High
doses of T induce a significant increase of AR expression during
proliferation and differentiation. Little information is available
on AR targets that drive the myogenic process. In our study, testosterone
induces myogenin, myosin heavy chains (MyHC) and GRIP-1 expression,
suggesting that AR and its coregulatory proteins are pivotal factors
in skeletal muscle differentiation.},
issn = {0303-7207},
keywords = {Androgen receptor, Testosterone, Skeletal muscle},
url = {http://www.sciencedirect.com/science/article/B6T3G-4SPC0TW-1/2/7f4d722d2ec06bdf88bc2ec54c87a42f}
}
@ARTICLE{Wanninger2011,
author = {Josef Wanninger and Roland Walter and Sabrina Bauer and Kristina
Eisinger and Andreas Schäffler and Christoph Dorn and Thomas S.
Weiss and Claus Hellerbrand and Christa Buechler},
title = {MMP-9 activity is increased by adiponectin in primary human hepatocytes
but even negatively correlates with serum adiponectin in a rodent
model of non-alcoholic steatohepatitis},
journal = {Experimental and Molecular Pathology},
year = {2011},
volume = {91},
pages = {603 - 607},
number = {2},
abstract = {Adiponectin protects from inflammation and fibrosis in metabolic liver
disease. In the present study we analyzed whether this adipokine
may directly affect the activity of matrix metalloproteinases (MMPs),
central regulators of fibrinolysis, in hepatocytes. Global gene expression
analysis indicated upregulation of MMP-9 and tissue inhibitor of
metalloproteinases-1 (TIMP-1) expression in primary human hepatocytes
(PHH) in response to stimulation with adiponectin, and these results
were confirmed by real-time RT-PCR. Furthermore, gelatin zymography
revealed that MMP-9 activity was significantly induced in supernatants
of adiponectin stimulated PHHs. In a murine model of hepatic steatosis
and in human steatotic liver samples hepatic MMP-9 activity was not
significantly altered. However, in two different murine models of
non-alcoholic steatohepatitis (NASH) MMP-9 activity was significantly
elevated compared to chow fed control mice. Of note, MMP-9 activity
did not or even negatively, respectively, correlate with adiponectin
serum levels in these models.
The current data indicate that in NASH hepatic inflammation and fibrosis
but not hepatic steatosis induce liver MMP-9 activity, and this induction
seems to be related to the anti-inflammatory activity of adiponectin
rather than its effect on hepatocellular MMP-9 expression.},
doi = {10.1016/j.yexmp.2011.07.001},
issn = {0014-4800},
keywords = {Liver fibrosis},
url = {http://www.sciencedirect.com/science/article/pii/S001448001100089X}
}
@ARTICLE{Wapenaar2004,
author = {Wapenaar, Martin C. and van Belzen, Martine J. and Fransen, Justin
H. and Fariña Sarasqueta, Aranzazu and Houwen, Roderick H. J. and
Meijer, Jos W. R. and Mulder, Chris J. J. and Wijmenga, Cisca},
title = {The interferon gamma gene in celiac disease: augmented expression
correlates with tissue damage but no evidence for genetic susceptibility},
journal = {Journal of Autoimmunity},
year = {2004},
volume = {23},
pages = {183--190},
number = {2},
month = sep,
abstract = {Celiac disease (CD) is a complex genetic disorder characterized by
gluten intolerance. The Th1 immune response, with a key position
for interferon gamma (IFN-[gamma]), is an important determinant of
intestinal remodeling in CD. We aimed at further ascertaining the
role of IFN-[gamma], either as a genetic factor in the etiology,
or as a facilitator of disease initiation/progression. Duodenal biopsies
were sampled across distinct histopathological stages of the disease,
including refractory CD (RCD), and used to determine IFN-[gamma]
gene (IFNG) expression by real-time RT-PCR. INFG expression correlated
with the extent of tissue restructuring, reaching a 240-fold higher
expression in total villous atrophy compared to healthy tissue. CD
and RCD patients with similar lesions had comparable expression levels.
Interestingly, patients in complete remission still had 7.6-fold
residual over-expression. An INFG marker was tested in three cohorts
of Dutch patients for both genetic linkage and association. Linkage
analysis yielded no significant scores for IFNG or its flanking markers.
In addition, IFNG allele frequencies were not differently distributed
between cases and controls. Likewise, all alleles were randomly transmitted
to affected children in parents-case trios. There is no evidence
for IFNG as a predisposing gene in CD, despite its enhanced expression
in patients in complete remission.},
issn = {0896-8411},
keywords = {Celiac disease, Gene expression, Genetics, Interferon gamma, Intestinal
mucosa},
url = {http://www.sciencedirect.com/science/article/B6WHC-4CWBJRN-2/2/21172f2666ae69962a7442d7a58395a8}
}
@ARTICLE{Wapinski2010,
author = {Wapinski, Ilan and Pfiffner, Jenna and French, Courtney and Socha,
Amanda and Thompson, Dawn Anne and Regev, Aviv},
title = {Gene duplication and the evolution of ribosomal protein gene regulation
in yeast},
journal = {PNAS},
year = {2010},
volume = {107},
pages = {5505--5510},
number = {12},
month = mar,
abstract = {Coexpression of genes within a functional module can be conserved
at great evolutionary distances, whereas the associated regulatory
mechanisms can substantially diverge. For example, ribosomal protein
(RP) genes are tightly coexpressed in Saccharomyces cerevisiae, but
the cis and trans factors associated with them are surprisingly diverged
across Ascomycota fungi. Little is known, however, about the functional
impact of such changes on actual expression levels or about the selective
pressures that affect them. Here, we address this question in the
context of the evolution of the regulation of RP gene expression
by using a comparative genomics approach together with cross-species
functional assays. We show that an activator (Ifh1) and a repressor
(Crf1) that control RP gene regulation in normal and stress conditions
in S. cerevisiae are derived from the duplication and subsequent
specialization of a single ancestral protein. We provide evidence
that this regulatory innovation coincides with the duplication of
RP genes in a whole-genome duplication (WGD) event and may have been
important for tighter control of higher levels of RP transcripts.
We find that subsequent loss of the derived repressor led to the
loss of a stress-dependent repression of RPs in the fungal pathogen
Candida glabrata. Our comparative computational and experimental
approach shows how gene duplication can constrain and drive regulatory
evolution and provides a general strategy for reconstructing the
evolutionary trajectory of gene regulation across species.},
url = {http://www.pnas.org/cgi/content/abstract/107/12/5505}
}
@ARTICLE{Ward2011,
author = {Heather H. Ward and Elsa Romero and Angela Welford and Gavin Pickett
and Robert Bacallao and Vincent H. Gattone II and Scott A. Ness and
Angela Wandinger-Ness and Tamara Roitbak},
title = {Adult human CD133/1+ kidney cells isolated from papilla integrate
into developing kidney tubules},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
year = {2011},
volume = {1812},
pages = {1344 - 1357},
number = {10},
note = {Molecular Mechanisms of Polycystic Kidney Disease},
abstract = {Approximately 60,000 patients in the United States are waiting for
a kidney transplant due to genetic, immunologic and environmentally
caused kidney failure. Adult human renal stem cells could offer opportunities
for autologous transplant and repair of damaged organs. Current data
suggest that there are multiple progenitor types in the kidney with
distinct localizations. In the present study, we characterize cells
derived from human kidney papilla and show their capacity for tubulogenesis.
In situ, nestin+ and CD133/1+ cells were found extensively intercalated
between tubular epithelia in the loops of Henle of renal papilla,
but not of the cortex. Populations of primary cells from the renal
cortex and renal papilla were isolated by enzymatic digestion from
human kidneys unsuited for transplant and immuno-enriched for CD133/1+
cells. Isolated CD133/1+ papillary cells were positive for nestin,
as well as several human embryonic stem cell markers (SSEA4, Nanog,
SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial
and neuronal-like phenotypes. Isolated papillary cells exhibited
morphologic plasticity upon modulation of culture conditions and
inhibition of asymmetric cell division. Labeled papillary cells readily
associated with cortical tubular epithelia in co-culture and 3-dimensional
collagen gel cultures. Heterologous organ culture demonstrated that
CD133/1+ progenitors from the papilla and cortex became integrated
into developing kidney tubules. Tubular epithelia did not participate
in tubulogenesis. Human renal papilla harbor cells with the hallmarks
of adult kidney stem/progenitor cells that can be amplified and phenotypically
modulated in culture while retaining the capacity to form new kidney
tubules. This article is part of a Special Issue entitled: Polycystic
Kidney Disease.},
doi = {10.1016/j.bbadis.2011.01.010},
issn = {0925-4439},
keywords = {Kidney disease},
url = {http://www.sciencedirect.com/science/article/pii/S0925443911000238}
}
@ARTICLE{Ward2006,
author = {Ward, Nancy E. and Pellis, Neal R. and Risin, Semyon A. and Risin,
Diana},
title = {Gene expression alterations in activated human T-cells induced by
modeled microgravity},
journal = {J. Cell. Biochem.},
year = {2006},
volume = {99},
pages = {1187--1202},
number = {4},
abstract = {Abstract 10.1002/jcb.20988.abs Studies conducted in real Space and
in ground-based microgravity analog systems (MAS) have demonstrated
changes in numerous lymphocyte functions. In this investigation we
explored whether the observed functional changes in lymphocytes in
MAS are associated with changes in gene expression. NASA-developed
Rotating Wall Vessel (RWV) bioreactor was utilized as a MAS. Activated
T lymphocytes were obtained by adding 100 ng/ml of anti-CD3 and 100
U/ml of IL-2 in RPMI medium to blood donor mononuclear cells for
4 days. After that the cells were washed and additionally cultured
for up to 2 weeks with media (RPMI, 10% FBS and 100 U/ml IL-2) replacement
every 3–4 days. Flow cytometry analysis had proven that activated
T lymphocytes were the only cells remaining in culture by that time.
They were split into two portions, cultured for additional 24 h in
either static or simulated microgravity conditions, and used for
RNA extraction. The gene expression was assessed by Affymetrix GeneChip®
Human U133A array allowing screening for expression of 18,400 genes.
About 4–8% of tested genes responded to MG by more than a 1.5-fold
change in expression; however, reproducible changes were observed
only in 89 genes. Ten of these genes were upregulated and 79 were
downregulated. These genes were categorized by associated pathways
and viewed graphically through histogram analysis. Separate histograms
of each pathway were then constructed representing individual gene
expression fold changes. Possible functional consequences of the
identified reproducible gene expression changes are discussed. J.
Cell. Biochem. 99: 1187–1202, 2006. © 2006 Wiley-Liss, Inc.},
issn = {1097-4644},
keywords = {immunity, human lymphocytes, gravitational biology, space physiology,
gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.20988}
}
@ARTICLE{Ward2006a,
author = {Ward, William O. and Delker, Don A. and Hester, Susan D. and Thai,
Sheau-Fung and Wolf, Douglas C. and Allen, James W. and Nesnow, Stephen},
title = {Transcriptional Profiles in Liver from Mice Treated with Hepatotumorigenic
and Nonhepatotumorigenic Triazole Conazole Fungicides: Propiconazole,
Triadimefon, and Myclobutanil},
journal = {Toxicol Pathol},
year = {2006},
volume = {34},
pages = {863--878},
number = {7},
month = dec,
abstract = {Conazoles are environmental and pharmaceutical fungicides. The present
study relates the toxicological effects of conazoles to alterations
of gene and pathway transcription and identifies potential modes
of tumorigenic action. In a companion study employing conventional
toxicological bioassays (Allen et al., 2006), male CD-1 mice were
fed triadimefon, propiconazole, or myclobutanil in a continuous oral-dose
regimen for 4, 30, or 90 days. These conazoles were found to induce
hepatomegaly, to induce high levels of hepatic pentoxyresorufin-O-dealkylase
activity, to increase hepatic cell proliferation, to decrease serum
cholesterol, and to increase serum triglycerides. Differentially
expressed genes and pathways were identified using Affymetrix GeneChips.
Gene-pathway associations were obtained from the Kyoto Encyclopedia
of Genes and Genomes, Biocarta, and MetaCore compendia. The pathway
profiles of each conazole were different at each time point. In general,
the number of altered metabolism, signaling, and growth pathways
increased with time and dose and were greatest with propiconazole.
All conazoles had effects on nuclear receptors as evidenced by increased
expression and enzymatic activities of a series of related cytochrome
P450s (CYP). A subset of altered genes and pathways distinguished
the three conazoles from each other. Triadimefon and propiconazole
both altered apoptosis, cell cycle, adherens junction, calcium signaling,
and EGFR signaling pathways. Triadimefon produced greater changes
in cholesterol biosynthesis and retinoic acid metabolism genes and
in selected signaling pathways. Propiconazole had greater effects
on genes responding to oxidative stress and on the IGF/P13K/AKt/PTEN/mTor
and Wnt-{beta}-catenin pathways. In conclusion, while triadimefon,
propiconazole, and myclobutanil had similar effects in mouse liver
on hepatomegaly, histology, CYP activities, cell proliferation, and
serum cholesterol, genomic analyses revealed major differences in
their gene expression profiles.},
url = {http://tpx.sagepub.com/cgi/content/abstract/34/7/863}
}
@ARTICLE{Wargelius2010,
author = {Wargelius, A. and Fjelldal, P. G. and Grini, A. and Gil-Martens,
L. and Kvamme, B.-O. and Hansen, T.},
title = {MMP-13 (Matrix MetalloProteinase 13) expression might be an indicator
for increased ECM remodeling and early signs of vertebral compression
in farmed Atlantic salmon (Salmo salar L.)},
journal = {Journal of Applied Ichthyology},
year = {2010},
volume = {26},
pages = {366--371},
number = {2},
abstract = {Summary Vertebral body compression is a common problem in commercial
farming of Atlantic salmon. Although risk factors, such as vaccination
and malnutrition, have been identified, the etiology is largely unknown.
Histological studies of Atlantic salmon have shown that in a compressed
deformity (platyspondyly) the length of the compact bone is reduced
while the notochord start to form atypical chrondrogenic structures.
In mammals, similar remodeling activities have been linked to inflammatory
processes in the tissue. Hence, we wanted to investigate whether
the compressed vertebrae in Atlantic salmon showed presence of local
(IL-1β, TNF-α1), systemic (IgM) and chronic (MMP-13, MMP-9) immune
responses (measured with quantitative PCR). Unvaccinated groups of
Atlantic salmon that would later develop high or low prevalence of
vertebral compression during on-growth in seawater were sampled at
seawater transfer, and 3 and 6Â weeks after seawater transfer. In
addition, compressed and normal vertebrae from the high deformity
prevalence group were sampled 44Â weeks after transfer to seawater.
MMP-13 was significantly up-regulated in the group that developed
a high prevalence of deformity, and also significantly up-regulated
in compressed vertebrae, 44Â weeks after seawater transfer. In compressed
vertebrae, MMP-13 was equally up-regulated in the notochord, compact
bone and trabecular bone. The results of the present study suggest
that MMP-13 may serve as an early indicator for bone remodeling which
may lead to vertebral compression, and that there is a relationship
between the development of vertebral compression and increased remodeling
activities in farmed Atlantic salmon.},
issn = {1439-0426},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0426.2010.01436.x}
}
@ARTICLE{Wargelius2010a,
author = {Wargelius, A. and Fjelldal, P. G. and Nordgarden, U. and Grini, A.
and Krossoy, C. and Grotmol, S. and Totland, G. K. and Hansen, T.},
title = {Collagen type XI {alpha}1 may be involved in the structural plasticity
of the vertebral column in Atlantic salmon (Salmo salar L.)},
journal = {J. Exp. Biol.},
year = {2010},
volume = {213},
pages = {1207--1216},
number = {7},
month = apr,
abstract = {Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity
in structure, osteoid secretion and mineralization in response to
photoperiod. Other properties of the vertebral bone, such as mineral
content and mechanical strength, are also associated with common
malformations in farmed Atlantic salmon. The biological mechanisms
that underlie these changes in bone physiology are unknown, and in
order to elucidate which factors might be involved in this process,
microarray assays were performed on vertebral bone of Atlantic salmon
reared under natural or continuous light. Eight genes were upregulated
in response to continuous light treatment, whereas only one of them
was upregulated in a duplicate experiment. The transcriptionally
regulated gene was predicted to code for collagen type XI {alpha}1,
a protein known to be involved in controlling the diameter of fibrillar
collagens in mammals. Furthermore, the gene was highly expressed
in the vertebrae, where spatial expression was found in trabecular
and compact bone osteoblasts and in the chordoblasts of the notochordal
sheath. When we measured the expression level of the gene in the
tissue compartments of the vertebrae, the collagen turned out to
be 150 and 25 times more highly expressed in the notochord and compact
bone respectively, relative to the expression in the trabecular bone.
Gene expression was induced in response to continuous light, and
reduced in compressed vertebrae. The downregulation in compressed
vertebrae was due to reduced expression in the compact bone, while
expression in the trabecular bone and the notochord was unaffected.
These data support the hypothesis that this gene codes for a presumptive
collagen type XI {alpha}1, which may be involved in the regulatory
pathway leading to structural adaptation of the vertebral architecture.},
url = {http://jeb.biologists.org/cgi/content/abstract/213/7/1207}
}
@ARTICLE{Waring2008,
author = {Waring, Jeffrey F. and Abel, Stephen and Li, Jinhe and Bitner, R.
Scott and Nikkel, Arthur L. and Blomme, Eric A. and Anderson, David
J. and Gopalakrishnan, Murali},
title = {Analysis of gene expression profiles in rat hippocampus following
treatment with nicotine and an [alpha]7 nAChR selective agonist},
journal = {Neuroscience Research},
year = {2008},
volume = {60},
pages = {266--274},
number = {3},
month = mar,
abstract = {The nicotinic acetylcholine receptors (nAChRs) play critical roles
in neuronal transmission and modulation. Among the diverse nAChRs,
the [alpha]7 subtype has been considered as a potential therapeutic
target for treating cognitive deficits associated with neuropsychiatric
and neurodegenerative diseases. Although a number of mechanisms including
neurotransmitter and biochemical effects linking [alpha]7 nAChR activation
and cognitive function are beginning to be described, the underlying
molecular processes especially following repeated administration
remain unclear. To address this, we have performed gene expression
analysis in rats treated with nicotine and a selective [alpha]7 nAChR
agonist, PNU-282987. Our results showed significant overlap in gene
expression changes induced by PNU-282987 and nicotine, suggesting
convergent pathways triggered by these compounds. Treatment with
nicotine also resulted in regulation of a number of genes that were
not regulated by PNU-282987, consistent with the interaction of nicotine
with other nAChRs beyond the [alpha]7 subtype. Interestingly, these
gene expression changes were observed 24 h post-dose, suggesting
that both nicotine and PNU-282987 cause protracted changes in gene
expression. Overall, our results identify gene expression changes
that may contribute to further defining the roles of nAChR activation
in cognitive function.},
issn = {0168-0102},
keywords = {Nicotine, Nicotinic receptor, Microarray, Gene expression, Alzheimer's
disease, Transcription},
url = {http://www.sciencedirect.com/science/article/B6T0H-4R68N7C-1/2/9d9908e479c351eae89f17e4f5b48744}
}
@ARTICLE{Waring2003,
author = {Waring, Jeffrey F. and Ciurlionis, Rita and Clampit, Jill E. and
Morgan, Sherry and Gum, Rebecca J. and Jolly, Robert A. and Kroeger,
Paul and Frost, Leigh and Trevillyan, James and Zinker, Bradley A.
and Jirousek, Michael and Ulrich, Roger G. and Rondinone, Cristina
M.},
title = {PTP1B antisense-treated mice show regulation of genes involved in
lipogenesis in liver and fat},
journal = {Molecular and Cellular Endocrinology},
year = {2003},
volume = {203},
pages = {155--168},
number = {1-2},
month = may,
abstract = {Protein tyrosine phosphatases are important regulators of insulin
signal transduction. Our studies have shown that in insulin resistant
and diabetic ob/ob and db/db mice, reducing the levels of protein
tyrosine phosphatase 1B (PTP1B) protein by treatment with a PTP1B
antisense oligonucleotide resulted in improved insulin sensitivity
and normalized plasma glucose levels. The mechanism by which PTP1B
inhibition improves insulin sensitivity is not fully understood.
We have used microarray analysis to compare gene expression changes
in adipose tissue, liver and muscle of PTP1B antisense-treated ob/ob
mice. Our results show that treatment with PTP1B antisense resulted
in the downregulation of genes involved in lipogenesis in both fat
and liver, and a downregulation of genes involved in adipocyte differentiation
in fat, suggesting that PTP1B antisense acts through a different
mechanism than thiazolidinedione (TZD) treatment. In summary, microarray
results suggest that reduction of PTP1B may alleviate hyperglycemia
and enhance insulin sensitivity by a different mechanism than TZD
treatment.},
issn = {0303-7207},
keywords = {Microarray, Diabetes, PTP1B, Antisense, ob/ob mice, Lipogenesis},
url = {http://www.sciencedirect.com/science/article/B6T3G-487DY8P-2/2/cda42f863cb174e94ad38a1645e9e713}
}
@ARTICLE{Waring2002,
author = {Waring, Jeffrey F and Gum, Rebecca and Morfitt, David and Jolly,
Robert A and Ciurlionis, Rita and Heindel, Matthew and Gallenberg,
Lori and Buratto, Bruno and Ulrich, Roger G},
title = {Identifying toxic mechanisms using DNA microarrays: evidence that
an experimental inhibitor of cell adhesion molecule expression signals
through the aryl hydrocarbon nuclear receptor},
journal = {Toxicology},
year = {2002},
volume = {181-182},
pages = {537--550},
month = dec,
abstract = {Microarray analysis of gene expression has become a powerful approach
for exploring the biological effects of drugs and other chemicals.
In toxicology research, gene expression profiling may help identify
hazards by comparing results for an experimental compound with a
database, and establish mechanistic hypotheses through examination
of discrete gene changes. Here we examine the hepatic effects of
a thienopyridine inhibitor of NF-[kappa]B-mediated expression of
cellular adhesion proteins. In a 3-day toxicity study in Sprague-Dawley
rats, A-277249 induced hypertrophy of the liver and elevated serum
levels of alanine aminotransferase (ALT), aspartate aminotransferase
(AST) and alkaline phosphatase (ALP). To investigate mechanism, microarray
analysis was done on RNA from livers of A-277249-treated rats. Gene
expression profiles from A-277249 were compared with a database of
profiles from fifteen known hepatotoxins. Agglomerative hierarchical
cluster analysis showed A-277249 to have a profile most similar to
the aromatic hydrocarbons Aroclor 1254 and 3-methylcholanthrene (3MC),
two known activators of the aryl hydrocarbon nuclear receptor (AhR).
Several genes regulated by the AhR, including cytochrome P450 1A1,
were upregulated by A-277249. In addition, several genes involved
in apoptosis and cell cycle were differentially expressed consistent
with cell turnover, hypertrophy and hyperplasia observed by histology.
Results from this study indicate that A-277249 hepatic toxicity is
mediated by the AhR either directly or through effects on NF-[kappa]B,
and demonstrate the utility of microarray analysis for the rapid
identification of toxic hazards for new chemical entities.},
issn = {0300-483X},
keywords = {Microarray, Hepatotoxin, Hepatic toxicity, Gene expression, NF-[kappa]B,
Aryl hydrocarbon receptor},
url = {http://www.sciencedirect.com/science/article/B6TCN-47DTB1R-1/2/c1299344113e6ed03dc4fe8c637e1207}
}
@ARTICLE{Waring2006,
author = {Waring, Jeffrey F. and Liguori, Michael J. and Luyendyk, James P.
and Maddox, Jane F. and Ganey, Patricia E. and Stachlewitz, Robert
F. and North, Colin and Blomme, Eric A. G. and Roth, Robert A.},
title = {Microarray Analysis of Lipopolysaccharide Potentiation of Trovafloxacin-Induced
Liver Injury in Rats Suggests a Role for Proinflammatory Chemokines
and Neutrophils},
journal = {J. Pharmacol. Exp. Ther.},
year = {2006},
volume = {316},
pages = {1080--1087},
number = {3},
month = mar,
abstract = {Idiosyncratic drug toxicity refers to toxic reactions occurring in
a small subset of patients and usually cannot be predicted during
preclinical or early phases of clinical trials. One hypothesis for
the pathogenesis of hepatic idiosyncratic drug reactions is that,
in certain individuals, underlying inflammation results in sensitization
of the liver, such that injury occurs from an agent that typically
would not cause hepatotoxicity at a therapeutic dose. We explored
this possibility by cotreating rats with nonhepatotoxic doses of
bacterial lipopolysaccharide (LPS) and trovafloxacin (TVX), a drug
that caused idiosyncratic hepatotoxicity in humans. The combination
of LPS and TVX resulted in hepatotoxicity in rats, as determined
by increases in serum alanine aminotransferase activity and hepatocellular
necrosis, which were not observed with either agent alone. In contrast,
treatment with LPS and levofloxacin, a fluoroquinolone without human
idiosyncratic liability, did not result in these changes. Liver gene
expression analysis identified unique changes induced by the combination
of TVX and LPS, including enhanced expression of chemokines, suggestive
of liver neutrophil (PMN) accumulation and activation. Consistent
with a role for PMN in the hepatotoxicity induced by LPS/TVX, prior
depletion of PMN attenuated the liver injury. The results suggest
that gene expression profiles predictive of idiosyncratic liability
can be generated in rats cotreated with LPS and drug. Furthermore,
they identify gene expression changes that could be explored as biomarkers
for idiosyncratic toxicity and lead to enhanced understanding of
the mechanism(s) underlying hepatotoxicity induced by TVX.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/316/3/1080}
}
@ARTICLE{Waring2008a,
author = {Waring, Jeffrey F. and Yang, Yi and Healan-Greenberg, Christine H.
and Adler, Andrew L. and Dickinson, Robert and McNally, Teresa and
Wang, Xiaojun and Weitzberg, Moshe and Xu, Xiangdong and Lisowski,
Andrew and Warder, Scott E. and Gu, Yu Gui and Zinker, Bradley A.
and Blomme, Eric A. and Camp, Heidi S.},
title = {Gene Expression Analysis in Rats Treated with Experimental Acetyl-Coenzyme
A Carboxylase Inhibitors Suggests Interactions with the Peroxisome
Proliferator-Activated Receptor {alpha} Pathway},
journal = {J. Pharmacol. Exp. Ther.},
year = {2008},
volume = {324},
pages = {507--516},
number = {2},
month = feb,
abstract = {Acetyl CoA carboxylase (ACC) 2, which catalyzes the carboxylation
of acetyl-CoA to form malonyl-CoA, has been identified as a potential
target for type 2 diabetes and obesity. Small-molecule inhibitors
of ACC2 would be expected to reduce de novo lipid synthesis and increase
lipid oxidation. Treatment of ob/ob mice with compound A-908292 (S)
({(S)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic
acid methyl ester), a small-molecule inhibitor with an IC50 of 23
nM against ACC2, resulted in a reduction of serum glucose and triglyceride
levels. However, compound A-875400 (R) ({(R)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic
acid methyl ester), an inactive enantiomer of A-908292 (S) with approximately
50-fold less activity against ACC2, also caused a similar reduction
in glucose and triglycerides, suggesting that the glucose-lowering
effects in ob/ob mice may be mediated by other metabolic pathways
independent of ACC2 inhibition. To characterize the pharmacological
activity of these experimental compounds at a transcriptional level,
rats were orally dosed for 3 days with either A-908292 (S) or A-875400
(R), and gene expression analysis was performed. Gene expression
analysis of livers showed that treatment with A-908292 (S) or A-875400
(R) resulted in gene expression profiles highly similar to known
peroxisome proliferator-activated receptor (PPAR)-{alpha} activators.
The results suggest that, in vivo, both A-908292 (S) and A-875400
(R) stimulated the PPAR-{alpha}-dependent signaling pathway. These
results were further supported by both an in vitro genomic evaluation
using rat hepatocytes and immunohistochemical evaluation using 70-kDa
peroxisomal membrane protein. Overall, the gene expression analysis
suggests a plausible mechanism for the similar pharmacological findings
with active and inactive enantiomers of an ACC2 inhibitor.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/324/2/507}
}
@ARTICLE{Warneboldt2008,
author = {Warneboldt, Julia and Haller, Florian and Horstmann, Olaf and Danner,
Bernhard and Füzesi, László and Doenecke, Detlef and Happel, Nicole},
title = {Histone H1x is highly expressed in human neuroendocrine cells and
tumours},
journal = {BMC Cancer},
year = {2008},
volume = {8},
pages = {388},
number = {1},
abstract = {BACKGROUND:Histone H1x is a ubiquitously expressed member of the H1
histone family. H1 histones, also called linker histones, stabilize
compact, higher order structures of chromatin. In addition to their
role as structural proteins, they actively regulate gene expression
and participate in chromatin-based processes like DNA replication
and repair. The epigenetic contribution of H1 histones to these mechanisms
makes it conceivable that they also take part in malignant transformation.METHODS:Based
on results of a Blast data base search which revealed an accumulation
of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine
tumours (NETs), we evaluated the expression of H1x in NETs from lung
and the gastrointestinal tract using immunohistochemisty. Relative
protein and mRNA levels of H1x were analysed by Western blot analysis
and quantitative real-time RT-PCR, respectively. Since several reports
describe a change of the expression level of the replacement subtype
H1.0 during tumourigenesis, the analysis of this subtype was included
in this study.RESULTS:We found an increased expression of H1x but
not of H1.0 in NET tissues in comparison to corresponding normal
tissues. Even though the analysed NETs were heterogenous regarding
their grade of malignancy, all except one showed a considerably higher
protein amount of H1x compared with corresponding non-neoplastic
tissue. Furthermore, double-labelling of H1x and chromogranin A in
sections of pancreas and small intestine revealed that H1x is highly
expressed in neuroendocrine cells of these tissues.CONCLUSION:We
conclude that the high expression of histone H1x in NETs is probably
due to the abundance of this protein in the cells from which these
tumours originate.},
doi = {10.1186/1471-2407-8-388},
issn = {1471-2407},
pubmedid = {19108733},
url = {http://www.biomedcentral.com/1471-2407/8/388}
}
@ARTICLE{Warner2011,
author = {Dennis R. Warner and Partha Mukhopadhyay and Guy N. Brock and Vasyl
Pihur and M. Michele Pisano and Robert M. Greene},
title = {TGF?-1 and Wnt-3a interact to induce unique gene expression profiles
in murine embryonic palate mesenchymal cells},
journal = {Reproductive Toxicology},
year = {2011},
volume = {31},
pages = {128 - 133},
number = {2},
abstract = {Development of the secondary palate in mammals is a complex process
under the control of numerous growth and differentiation factors
that regulate key processes such as cell proliferation, synthesis
of extracellular matrix molecules, and epithelial–mesenchymal transdifferentiation.
Alterations in any one of these processes either through genetic
mutation or environmental insult have the potential to lead to clefts
of the secondary palate. Members of the TGFβ family of cytokines
are crucial mediators of these processes and emerging evidence supports
a pivotal role for members of the Wnt family of secreted growth and
differentiation factors. Previous work in this laboratory demonstrated
cross-talk between the Wnt and TGFβ signaling pathways in cultured
mouse embryonic palate mesenchymal cells. In the current study we
tested the hypothesis that unique gene expression profiles are induced
in murine embryonic palate mesenchymal cells as a result of this
cross-talk between the TGFβ and Wnt signal transduction pathways.},
doi = {10.1016/j.reprotox.2010.10.006},
issn = {0890-6238},
keywords = {Embryo},
url = {http://www.sciencedirect.com/science/article/pii/S0890623810003175}
}
@ARTICLE{Warner2011a,
author = {Warner, Dennis R. and Mukhopadhyay, Partha and Brock, Guy N. and
Pihur, Vasyl and Pisano, M. Michele and Greene, Robert M.},
title = {TGF[beta]-1 and Wnt-3a interact to induce unique gene expression
profiles in murine embryonic palate mesenchymal cells},
journal = {Reproductive Toxicology},
year = {2011},
volume = {31},
pages = {128--133},
number = {2},
month = feb,
abstract = {Development of the secondary palate in mammals is a complex process
under the control of numerous growth and differentiation factors
that regulate key processes such as cell proliferation, synthesis
of extracellular matrix molecules, and epithelial-mesenchymal transdifferentiation.
Alterations in any one of these processes either through genetic
mutation or environmental insult have the potential to lead to clefts
of the secondary palate. Members of the TGF[beta] family of cytokines
are crucial mediators of these processes and emerging evidence supports
a pivotal role for members of the Wnt family of secreted growth and
differentiation factors. Previous work in this laboratory demonstrated
cross-talk between the Wnt and TGF[beta] signaling pathways in cultured
mouse embryonic palate mesenchymal cells. In the current study we
tested the hypothesis that unique gene expression profiles are induced
in murine embryonic palate mesenchymal cells as a result of this
cross-talk between the TGF[beta] and Wnt signal transduction pathways.},
issn = {0890-6238},
keywords = {Embryo, Palate, TGF[beta], Wnt, Microarray, Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S0890623810003175}
}
@ARTICLE{Warner2012,
author = {Jillian Warner and Janet Rose Osuch and Wilfried Karmaus and Jeffrey
R. Landgraf and Bonita Taffe and Michael O'Keefe and Dorota Mikucki
and Pam Haan},
title = {Common classification schemes for PCB congeners and the gene expression
of CYP17, CYP19, ESR1 and ESR2},
journal = {Science of The Total Environment},
year = {2012},
volume = {414},
pages = {81 - 89},
number = {0},
abstract = {Background Reliable techniques to measure polychlorinated biphenyl
(PCB) congeners make the clearer definition of their effects on human
health possible. Given that PCBs are classified as endocrine disrupters,
we sought to explore the expression of some key genes involved in
sex steroid metabolism. Objectives To examine common classification
schemes of PCB congeners and determine whether exposure to groups
classified by mechanism of action alter the gene expression (GE)
of CYP17, CYP19, and ESR1 and ESR2. Methods GE and exposure to various
classifications of lipid-adjusted PCB congeners were examined in
139 daughters of the Michigan Fisheaters' Cohort. Using mixed models
analyses and adjusting for age, menopausal status, and current use
of oral contraceptives and hormone replacement therapy, GE data were
regressed on exposure to PCB congener groupings based on mechanism
of action. Results Three novel findings are elucidated: first, that
up-regulation of CYP19 expression is associated with exposure to
PCB groupings containing dioxin-like, potentially anti-estrogenic,
immunotoxic congeners, including PCB IUPAC #74, #105, #118, #138,
#156, #157, #158, #167, and #170 from this cohort. Second, that exposure
to similar congeners (PCB IUPAC #105, #156, #157, #158, and #167
in this cohort) but using a classification based solely on hormonal
mechanisms of action is associated with increased expression of ESR2.
Third, that increased expression of CYP17 is of borderline significance
when associated with exposure to PCB IUPAC #118, #138, and #156.
Conclusions These findings are both counter-intuitive and intriguing.
Rather than exhibiting anti-estrogenic effects alone, they suggest
that these congeners up-regulate the major enzyme involved in estrogen
synthesis and tend to confirm previous findings of links between
AhR and ER signaling pathways. Replication of these findings, expansion
of the number of genes examined, exploration of mixtures of environmental
chemicals, and subsequent study of health outcomes in a larger cohort
are future priorities.},
doi = {10.1016/j.scitotenv.2011.10.044},
issn = {0048-9697},
keywords = {Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S004896971101237X}
}
@ARTICLE{Warner2003,
author = {Warner, Kristy A. and Crawford, Erin L. and Zaher, Aiman and Coombs,
Robert J. and Elsamaloty, Haitham and Roshong-Denk, Stacie L. and
Sharief, Imran and Amurao, Guillermo V. and Yoon, Yongsook and Al-Astal,
Amro Y. and Assaly, Ragheb A. and Hernandez, Dawn-Alita R. and Graves,
Timothy G. and Knight, Charles R. and Harr, Michael W. and Sheridan,
Todd B. and DeMuth, Jeffrey P. and Zahorchak, Robert J. and Hammersley,
Jeffrey R. and Olson, Dan E. and Durham, Samuel J. and Willey, James
C.},
title = {The c-myc x E2F-1/p21 Interactive Gene Expression Index Augments
Cytomorphologic Diagnosis of Lung Cancer in Fine-Needle Aspirate
Specimens},
journal = {J. Mol. Diagn.},
year = {2003},
volume = {5},
pages = {176--183},
number = {3},
month = aug,
abstract = {Morphological analysis of cytologic samples obtained by fine-needle
aspirate (FNA) or bronchoscopy is an important method for diagnosing
bronchogenic carcinoma. However, this approach has only about 65
to 80% diagnostic sensitivity. Based on previous studies, the c-myc
x E2F-1/p21WAF1/CIP1 (p21 hereafter) gene expression index is highly
sensitive and specific for distinguishing normal from malignant bronchial
epithelial tissues. In an effort to improve sensitivity of diagnosing
lung cancer in cytologic specimens, we used Standardized Reverse
Transcriptase Polymerase Chain Reaction (StaRT-PCR) to measure the
c-myc x E2F-1/p21 index in cDNA samples from 14 normal lung samples
(6 normal lung parenchyma and 8 normal bronchial epithelial cell
[NBEC] biopsies), and 16 FNA biopsies from 14 suspected tumors. Based
on cytomorphologic criteria, 11 of the 14 suspected tumors were diagnosed
as bronchogenic carcinoma and three specimens were non-diagnostic.
Subsequent biopsy samples confirmed that the three non-diagnostic
samples were derived from lung carcinomas. The index value for each
bronchogenic carcinoma was above a cut-off value of 7000 and the
index value of all but one normal sample was below 7000. Thus the
c-myc x E2F-1/p21 index may augment cytomorphologic diagnosis of
bronchogenic carcinoma biopsy samples, particularly those considered
non-diagnostic by cytomorphologic criteria.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/5/3/176}
}
@ARTICLE{Warnke2011,
author = {Warnke, Ines and Goralczyk, Regina and Fuhrer, Erna and Schwager,
Joseph},
title = {Dietary constituents reduce lipid accumulation in murine C3H10 T1/2
adipocytes: A novel fluorescent method to quantify fat droplets},
journal = {Nutrition \& Metabolism},
year = {2011},
volume = {8},
pages = {30},
number = {1},
abstract = {BACKGROUND:Adipocyte volume (fat accumulation) and cell number (adipogenesis)
is increased in obese individuals. Our objective was the identification
of dietary constituents with inhibitory effects on triglyceride formation
during adipogenesis. Therefore an in vitro adipose cell assay in
murine C3H10 T1/2 cells was developed, which enabled rapid quantification
of intracellular fat droplet accumulation during adipocyte differentiation.
Results were corroborated by expression levels of several specific
adipogenic and lipogenic genes which are known to regulate triglyceride
accumulation.METHODS:C3H10 T1/2 adipocyte differentiation was conducted
with rosiglitazone in the presence of test compounds for 7 days.
Accumulation of intracellular lipid droplets was measured using the
Cellomics(R) ArrayScan(R) VTI HCS reader and SpotDetector(R) BioApplication
from ThermoFisher. Fluorescent images were automatically acquired
and analysed employing the fluorescent dyes BODIPY(R) 493/503 and
Hoechst 33342, for staining neutral lipids and localisation of nuclei,
respectively. The expression levels of adipogenic and lipogenic genes,
such as PPARalpha and PPARgamma, C/EBPalpha, aP2, adiponectin, LPL
and HSL, CPT-1beta, ACC1, Glut4 and FAS, were determined by quantitative
RT-PCR. Dietary ingredients including PUFAs, carotenoids, polyphenols
and catechins were tested for their effect on lipid accumulation.RESULTS:The
omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid
(EPA), the carotenoid beta-carotene and hydroxytyrosol exhibited
the strongest inhibitory effects on the rosiglitazone-stimulated
lipid formation. (all-E)-lycopene and epigallocatechin gallate (EGCG)
showed a moderate inhibition, whereas resveratrol did not reduce
fat droplet formation. Additionally, it was demonstrated that adipogenic
and lipogenic gene expression was attenuated. DHA, beta-carotene
and hydroxytyrosol inhibited the gene expression of PPARgamma, C/EBPalpha,
aP2 and CPT-1beta.CONCLUSION:This in vitro assay in differentiating
adipocytes enables automated detection and quantification of changes
in lipid droplet number, size and intensity. The observed inhibitory
effects of identified dietary constituents such as omega-3 PUFAs
and beta-carotene correlate with the modulation of genes involved
in adipocyte differentiation.},
doi = {10.1186/1743-7075-8-30},
issn = {1743-7075},
pubmedid = {21569430},
url = {http://www.nutritionandmetabolism.com/content/8/1/30}
}
@ARTICLE{Warren2011,
author = {Warren, Ashley E. and Boulianne-Larsen, Carla M. and Chandler, Christine
B. and Chiotti, Kami and Kroll, Evgueny and Miller, Scott R. and
Taddei, Francois and Sermet-Gaudelus, Isabelle and Ferroni, Agnes
and McInnerney, Kathleen and Franklin, Michael J. and Rosenzweig,
Frank},
title = {Genotypic and Phenotypic Variation in Pseudomonas aeruginosa Reveals
Signatures of Secondary Infection and Mutator Activity in Certain
Cystic Fibrosis Patients with Chronic Lung Infections},
journal = {Infect. Immun.},
year = {2011},
volume = {79},
pages = {4802-4818},
number = {12},
abstract = {Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis
lung is limited by genetic variation, which depends on rates of horizontal
gene transfer and mutation supply. Because each may increase following
secondary infection or mutator emergence, we sought to ascertain
the incidence of secondary infection and genetic variability in populations
containing or lacking mutators. Forty-nine strains collected over
3 years from 16 patients were phenotyped for antibiotic resistance
and mutator status and were genotyped by repetitive-sequence PCR
(rep-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus
sequence typing (MLST). Though phenotypic and genetic polymorphisms
were widespread and clustered more strongly within than between longitudinal
series, their distribution revealed instances of secondary infection.
Sequence data, however, indicated that interlineage recombination
predated initial strain isolation. Mutator series were more likely
to be multiply antibiotic resistant, but not necessarily more variable
in their nucleotide sequences, than nonmutators. One mutator and
one nonmutator series were sequenced at mismatch repair loci and
analyzed for gene content using DNA microarrays. Both were wild type
with respect to mutL, but mutators carried an 8-bp mutS deletion
causing a frameshift mutation. Both series lacked 126 genes encoding
pilins, siderophores, and virulence factors whose inactivation has
been linked to adaptation during chronic infection. Mutators exhibited
loss of severalfold more genes having functions related to mobile
elements, motility, and attachment. A 105-kb, 86-gene deletion was
observed in one nonmutator that resulted in loss of virulence factors
related to pyoverdine synthesis and elements of the multidrug efflux
regulon. Diminished DNA repair activity may facilitate but not be
absolutely required for rapid evolutionary change.},
doi = {10.1128/IAI.05282-11},
eprint = {http://iai.asm.org/cgi/reprint/79/12/4802.pdf},
url = {http://iai.asm.org/cgi/content/abstract/79/12/4802}
}
@ARTICLE{Warren2009,
author = {Warren, Cynthia A. and Paulhill, Kimberly J. and Davidson, Laurie
A. and Lupton, Joanne R. and Taddeo, Stella S. and Hong, Mee Young
and Carroll, Raymond J. and Chapkin, Robert S. and Turner, Nancy
D.},
title = {Quercetin May Suppress Rat Aberrant Crypt Foci Formation by Suppressing
Inflammatory Mediators That Influence Proliferation and Apoptosis},
journal = {J. Nutr.},
year = {2009},
volume = {139},
pages = {101--105},
number = {1},
month = jan,
abstract = {The flavonoid quercetin suppresses cell proliferation and enhances
apoptosis in vitro. In this study, we determined whether quercetin
protects against colon cancer by regulating the protein level of
phosphatidylinositol 3-kinase (PI 3-kinase) and Akt or by suppressing
the expression of proinflammatory mediators [cyclooxygenase (COX)-1,
COX-2, inducible nitric oxide synthase (iNOS)] during the aberrant
crypt (AC) stage. Forty male rats were randomly assigned to receive
diets containing quercetin (0 or 4.5 g/kg) and injected subcutaneously
with saline or azoxymethane (AOM; 2 times during wk 3 and 4). The
colon was resected 4 wk after the last AOM injection and samples
were used to determine high multiplicity AC foci (HMACF; foci with
>4 AC) number, colonocyte proliferation and apoptosis by immunohistochemistry,
expression of PI 3-kinase (p85 and p85{alpha} subunits) and Akt by
immunoblotting, and COX-1, COX-2, and iNOS expression by real time
RT-PCR. Quercetin-fed rats had fewer (P = 0.033) HMACF. Relative
to the control diet, quercetin lowered the proliferative index (P
= 0.035) regardless of treatment and diminished the AOM-induced elevation
in crypt column cell number (P = 0.044) and expansion of the proliferative
zone (P = 0.021). The proportion of apoptotic colonocytes in AOM-injected
rats increased with quercetin treatment (P = 0.014). Levels of p85
and p85{alpha} subunits of PI 3-kinase and total Akt were unaffected
by dietary quercetin. However, quercetin tended to suppress (P <
0.06) the expression of COX-1 and COX-2. Expression of iNOS was elevated
by AOM injection (P = 0.0001). In conclusion, quercetin suppresses
the formation of early preneoplastic lesions in colon carcinogenesis,
which occurred in concert with reductions in proliferation and increases
in apoptosis. It is possible the effects on proliferation and apoptosis
resulted from the tendency for quercetin to suppress the expression
of proinflammatory mediators.},
url = {http://jn.nutrition.org/cgi/content/abstract/139/1/101}
}
@ARTICLE{Warren2008,
author = {Warren, Rene L. and Freeman, John D. and Levesque, Roger C. and Smailus,
Duane E. and Flibotte, Stephane and Holt, Robert A.},
title = {Transcription of foreign DNA in Escherichia coli},
journal = {Genome Res.},
year = {2008},
volume = {18},
pages = {1798--1805},
number = {11},
month = nov,
abstract = {Propagation of heterologous DNA in E. coli host cells is central to
molecular biology. DNA constructs are often engineered for expression
of recombinant protein in E. coli, but the extent of incidental transcription
arising from natural regulatory sequences in cloned DNA remains underexplored.
Here, we have used programmable microarrays and RT-PCR to measure,
comprehensively, the transcription of H. influenzae, P. aeruginosa,
and human DNA propagating in E. coli as bacterial artificial chromosomes.
We find evidence that at least half of all H. influenzae genes are
transcribed in E. coli. Highly transcribed genes are principally
involved in energy metabolism, and their proximal promoter regions
are significantly enriched with E. coli {sigma}70 (also known as
RpoD) binding sites. H. influenzae genes acquired from an ancient
bacteriophage Mu insertion are also highly transcribed. Compared
with H. influenzae, a smaller proportion of P. aeruginosa genes are
transcribed in E. coli, and in E. coli there is punctuated transcription
of human DNA. The presence of foreign DNA in E. coli disturbs the
host transcriptional profile, with expression of the E. coli phage
shock protein operon and the flagellar gene cluster being particularly
strongly up-regulated. While cross-species transcriptional activation
is expected to be enabling for horizontal gene transfer in bacteria,
incidental expression of toxic genes can be problematic for DNA cloning.
Ongoing characterization of cross-expression will help inform the
design of biosynthetic gene clusters and synthetic microbial genomes.},
url = {http://genome.cshlp.org/cgi/content/abstract/18/11/1798}
}
@ARTICLE{Wasserman2002,
author = {Wasserman, Scott M. and Mehraban, Fuad and Komuves, Laszlo G. and
Yang, Ruey-Bing and Tomlinson, James E. and Zhang, Ying and Spriggs,
Frank and Topper, James N.},
title = {Gene expression profile of human endothelial cells exposed to sustained
fluid shear stress},
journal = {Physiol Genomics},
year = {2002},
volume = {12},
pages = {13--23},
number = {1},
month = dec,
abstract = {Biomechanical forces can modulate endothelial phenotype through changes
in gene expression. We hypothesized that physiological laminar shear
stresses (LSS) act as differentiative stimuli on endothelial cells
(EC) to alter gene expression, creating an antioxidant, anti-apoptotic
and anti-proliferative environment. The transcriptional profile of
cultured human umbilical vein endothelial cells (HUVEC) exposed to
LSS was evaluated by GeneCalling; 107 genes demonstrated at least
a twofold change in expression at 24 h (LSS vs. static). These flow-responsive
genes represent a limited number of functional clusters that include
transcription factors, antioxidants, signaling molecules, cell cycle
regulators, and genes involved in cellular differentiation. Immunohistochemistry
and in situ hybridization confirmed that many of these flow-responsive
genes, including the novel basic helix-loop-helix transcription factor
Hath6, are expressed in EC in vivo. Thus these data identify a limited
set of flow-responsive genes expressed in the endothelium that may
be responsible for the establishment and maintenance of the flow-adapted
endothelial phenotype in vivo.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/12/1/13}
}
@ARTICLE{Watanabe2010,
author = {Watanabe, Futoshi and Kirkegaard, Mette and Matsumoto, Suguru and
Gont, Cecilia and Mannström, Paula and Ulfendahl, Mats and Fridberger,
Anders},
title = {Signaling through erbB receptors is a critical functional regulator
in the mature cochlea},
journal = {European Journal of Neuroscience},
year = {2010},
volume = {32},
pages = {717--724},
number = {5},
abstract = {Abstract Noise, ototoxic substances and various genetic factors are
common causes of profound hearing loss. Cochlear implants can often
restore hearing in these cases, but only if a sufficient number of
responsive auditory nerve fibers remain. Over time, these nerve fibers
degenerate in the damaged ear, and it is therefore important to establish
factors that control neuronal survival and maintain neural excitability.
Recent studies show that neuregulins and their receptors are important
for survival and proper targeting of neurons in the developing inner
ear. A role for neuregulins as maintainers of the neuronal population
in the mature inner ear was therefore hypothesized. Here, this hypothesis
was directly tested by chronic local application of substances that
block neuregulin receptors. Using auditory brainstem response measurements,
we demonstrate that such receptor block leads to a progressive hearing
impairment that develops over the course of weeks. This impairment
occurs despite a normal number of auditory neurons and preserved
outer hair cell function. Real-time quantitative reverse transcriptase-polymerase
chain reaction shows alterations in neurotrophin-3 expression, suggesting
that this growth factor participates in regulating cochlear sensitivity.
The present work demonstrates the critical importance of neuregulin/erbB
signaling in long-term functional regulation in the mature guinea
pig hearing organ.},
issn = {1460-9568},
keywords = {degeneration, hearing loss, neuregulins, spiral ganglion neurons},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1460-9568.2010.07347.x}
}
@ARTICLE{Watanabe2004,
author = {Watanabe, H and Suzuki, A and Goto, M and Ohsako, S and Tohyama,
C and Handa, H and Iguchi, T},
title = {Comparative uterine gene expression analysis after dioxin and estradiol
administration},
journal = {J. Mol. Endocrinol.},
year = {2004},
volume = {33},
pages = {763--771},
number = {3},
month = dec,
abstract = {The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
adversely affects many organisms. TCDD exposure is known to be associated
with abnormal development, hepatotoxicity and endocrine effects.
It has also been reported to have antiestrogenic activity in addition
to estrogenic activity. In order to clarify the effects of TCDD in
the uterus, we evaluated the patterns of gene expression after TCDD
and estradiol administration. Of the 10 000 arrayed genes, only a
few were affected by both estradiol and TCDD. Although the subset
of genes that responded to estrogen was also activated by TCDD, the
response to TCDD was more limited than that observed in response
to estradiol. Therefore, according to our analysis of gene expression
patterns, TCDD had partial and weak estrogenic activity in the uterus.},
url = {http://jme.endocrinology-journals.org/cgi/content/abstract/33/3/763}
}
@ARTICLE{Watanabe2011a,
author = {Watanabe, Keisuke and Takebayashi, Hirohide and Bepari, Asim K. and
Esumi, Shigeyuki and Yanagawa, Yuchio and Tamamaki, Nobuaki},
title = {Dpy19l1, a multi-transmembrane protein, regulates the radial migration
of glutamatergic neurons in the developing cerebral cortex},
journal = {Development},
year = {2011},
volume = {138},
pages = {4979-4990},
number = {22},
abstract = {During corticogenesis, the regulation of neuronal migration is crucial
for the functional organization of the neocortex. Glutamatergic neurons
are major excitatory components of the mammalian neocortex. In order
to elucidate the specific molecular mechanisms underlying their development,
we used single-cell microarray analysis to screen for mouse genes
that are highly expressed in developing glutamatergic neurons. We
identified dpy-19-like 1 (Dpy19l1), a homolog of C. elegans dpy-19,
which encodes a putative multi-transmembrane protein shown to regulate
directed migration of Q neuroblasts in C. elegans. At embryonic stages
Dpy19l1 is highly expressed in glutamatergic neurons in the mouse
cerebral cortex, whereas in the subpallium, where GABAergic neurons
are generated, expression was below detectable levels. Downregulation
of Dpy19l1 mediated by shRNA resulted in defective radial migration
of glutamatergic neurons in vivo, which was restored by the expression
of shRNA-insensitive Dpy19l1. Many Dpy19l1-knockdown cells were aberrantly
arrested in the intermediate zone and the deep layer and, additionally,
some extended single long processes towards the pial surface. Furthermore,
we observed defective radial migration of bipolar cells in Dpy19l1-knockdown
brains. Despite these migration defects, these cells correctly expressed
Cux1, which is a marker for upper layer neurons, suggesting that
Dpy19l1 knockdown results in migration defects but does not affect
cell type specification. These results indicate that Dpy19l1 is required
for the proper radial migration of glutamatergic neurons, and suggest
an evolutionarily conserved role for the Dpy19 family in neuronal
migration.},
doi = {10.1242/dev.068155},
eprint = {http://dev.biologists.org/cgi/reprint/138/22/4979.pdf},
url = {http://dev.biologists.org/cgi/content/abstract/138/22/4979}
}
@ARTICLE{Watanabe2012,
author = {Reiko Watanabe and Maria H. Morell and Josef M. Miller and Ariane
C. Kanicki and K. Sue O'Shea and Richard A. Altschuler and Yehoash
Raphael},
title = {Nestin-expressing cells in the developing, mature and noise-exposed
cochlear epithelium},
journal = {Molecular and Cellular Neuroscience},
year = {2012},
volume = {49},
pages = {104 - 109},
number = {2},
abstract = {The auditory sensory epithelium in non-mammalian vertebrates can replace
lost hair cells by transdifferentiation of supporting cells, but
this regenerative ability is lost in the mammalian cochlea. Future
cell-based treatment of hearing loss may depend on stem cell transplantation
or on transdifferentiation of endogenous cells in the cochlea. For
both approaches, identification of cells with stem cell features
within the mature cochlea may be useful. Here we use a Nestin-β-gal
mouse to examine the presence of Nestin positive cells in the mature
auditory epithelium, and determine how overstimulation of the ear
impacts these cells. Nestin positive cells were found in the apical
turn of the cochlea lateral to the outer hair cell area. This pattern
of expression persisted into mature age. The area of Nestin positive
cells was increased after the noise lesion. This increase in area
coincided with an increase in expression of the Nestin mRNA. The
data suggest that cells with potential stem cell features remain
in the mature mammalian cochlea, restricted to the apical turn, and
that an additional set of signals is necessary to trigger their contribution
to cell replacement therapy in the ear. As such, this population
of cells could serve to generate cochlear stem cells for research
and potential therapy, and may be a target for treatments based on
induced transdifferentiation of endogenous cochlear cells.},
doi = {10.1016/j.mcn.2011.11.001},
issn = {1044-7431},
keywords = {Cochlea},
url = {http://www.sciencedirect.com/science/article/pii/S1044743111002508}
}
@ARTICLE{Watanabe2012a,
author = {Watanabe, Satoru and Ohbayashi, Ryudo and Shiwa, Yuh and Noda, Aska
and Kanesaki, Yu and Chibazakura, Taku and Yoshikawa, Hirofumi},
title = {Light-dependent and asynchronous replication of cyanobacterial multi-copy
chromosomes},
journal = {Molecular Microbiology},
year = {2012},
pages = {no--no},
abstract = {While bacteria such as Escherichia coli and Bacillus subtilis harbor
a single circular chromosome, some freshwater cyanobacteria have
multiple chromosomes per cell. The detailed mechanism(s) of cyanobacterial
replication remains unclear. To elucidate the replication origin
(ori), form, and synchrony of the multi-copy genome in freshwater
cyanobacteria Synechococcus elongatus PCC 7942 we constructed strain
S. 7942TK that can incorporate 5-bromo-2′-deoxyuridine (BrdU) into
genomic DNA and analyzed its de novo DNA synthesis. The uptake of
BrdU was blocked under dark and resumed after transfer of the culture
to light conditions. Mapping analysis of nascent DNA fragments using
a next-generation sequencer indicated that replication starts bidirectionally
from a single ori, which locates in the upstream region of the dnaN
gene. Quantitative analysis of BrdU-labeled DNA and whole genome
sequence analysis indicated that the peak timing of replication precedes
that of cell division and that replication is initiated asynchronously
not only among cell populations but also among the multi-copy chromosomes.
Our findings suggest that replication initiation is regulated less
stringently in S. 7942 than in E. coli and B. subtilis.},
doi = {10.1111/j.1365-2958.2012.07971.x},
issn = {1365-2958},
keywords = {freshwater cyanobacteria, multi-copy genome, asynchronous replication,
replication origin},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2012.07971.x}
}
@ARTICLE{Watanabe2011,
author = {Watanabe, Toshiaki and Kobunai, Takashi and Yamamoto, Yoko and Ikeuchi,
Hiroki and Matsuda, Keiji and Ishihara, Soichiro and Nozawa, Keijiro
and Iinuma, Hisae and Kanazawa, Takamitsu and Tanaka, Toshiaki and
Yokoyama, Tadashi and Konishi, Tsuyoshi and Eshima, Kiyoshi and Ajioka,
Yohichi and Hibi, Toshifumi and Watanabe, Mamoru and Muto, Tetsuichiro
and Nagawa, Hirokazu},
title = {Predicting Ulcerative Colitis-Associated Colorectal Cancer Using
Reverse-Transcription Polymerase Chain Reaction Analysis},
journal = {Clinical Colorectal Cancer},
year = {2011},
volume = {10},
pages = {134--141},
number = {2},
month = jun,
abstract = {Background Widespread genetic alterations are present not only in
ulcerative colitis (UC)-associated neoplastic lesions but also in
the adjacent normal colonic mucosa. This suggests that genetic changes
in nonneoplastic mucosa might be effective markers for predicting
the development of UC-associated cancer (UC-Ca). This study aimed
to build a predictive model for the development of UC-Ca based on
gene expression levels measured by reverse-transcription polymerase
chain reaction (RT-PCR) analysis in nonneoplastic rectal mucosa.Patients
and Methods Fifty-three UC patients were examined, of which 10 had
UC-Ca and 43 did not (UC-NonCa). In addition to the 40 genes and
transcripts previously shown to be predictive for developing UC-Ca
in our microarray studies, 149 new genes, reported to be important
in carcinogenesis, were selected for low density array (LDA) analysis.
The expression of a total of 189 genes was examined by RT-PCR in
nonneoplastic rectal mucosa.Results We identified 20 genes showing
differential expression in UC-Ca and UC-NonCa patients, including
cancer-related genes such as CYP27B1, RUNX3, SAMSN1, EDIL3, NOL3,
CXCL9, ITGB2, and LYN. Using these 20 genes, we were able to build
a predictive model that distinguished patients with and without UC-Ca
with a high accuracy rate of 83% and a negative predictive value
of 100%.Conclusion This predictive model suggests that it is possible
to identify UC patients at a high risk of developing cancer. These
results have important implications for improving the efficacy of
surveillance by colonoscopy and suggest directions for future research
into the molecular mechanisms of UC-associated cancer.},
issn = {1533-0028},
keywords = {Dysplasia, Prediction, Neoplasia, Inflammatory bowel disease, RUNX3},
url = {http://www.sciencedirect.com/science/article/pii/S1533002811000120}
}
@ARTICLE{Waterbeemd2009,
author = {van de Waterbeemd, Bas and Streefland, Mathieu and Pennings, Jeroen
and van der Pol, Leo and Beuvery, Coen and Tramper, Johannes and
Martens, Dirk},
title = {Gene-expression-based quality scores indicate optimal harvest point
in Bordetella pertussis cultivation for vaccine production},
journal = {Biotechnol. Bioeng.},
year = {2009},
volume = {103},
pages = {900--908},
number = {5},
abstract = {Abstract 10.1002/bit.22326.abs The evolution of vaccine product quality
during batch cultivation of Bordetella pertussis, the causative agent
of whooping cough, was investigated with the goal to determine the
optimal harvest point. The process was explored by measuring mRNA
expression at frequent intervals during cultivation. The genes that
are involved in virulence are already known for this product and
changes in their expression levels are proposed to be indicative
for product quality. A quantitative product quality score is calculated
based on the expression levels of these virulence genes, which allows
comparison of expected product quality between culture samples. Product
quality scores were maximal throughout the logarithmic growth phase,
but dropped significantly at the start of the stationary phase. This
showed that the decreasing lactate and glutamate concentrations towards
the end of the batch are critical for product quality. On-line measurement
of these nutrients allows the cultivation process to be harvested
at the optimal harvest point, increasing process robustness and consistency.
Biotechnol. Bioeng. 2009;103: 900–908. © 2009 Wiley Periodicals,
Inc.},
issn = {1097-0290},
keywords = {Bordetella pertussis, harvest point, product quality, microarray,
transcriptome, batch cultivation, vaccine, process development},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22326}
}
@ARTICLE{Waterman2010,
author = {Waterman, Claire and Currie, Richard and Cottrell, Lisa and Dow,
Jacky and Wright, Jayne and Waterfield, Catherine and Griffin, Julian},
title = {An integrated functional genomic study of acute phenobarbital exposure
in the rat},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {9},
number = {1},
abstract = {BACKGROUND:Non-genotoxic carcinogens are notoriously difficult to
identify as they do not damage DNA directly and have diverse modes
of action, necessitating long term in vivo studies. The early effects
of the classic rodent non-genotoxic hepatocarcinogen phenobarbital
have been investigated in the Fisher rat using a combination of metabolomics
and transcriptomics, to investige early stage mechanistic changes
that are predictive of longer term pathology.RESULTS:Liver and blood
plasma were profiled across 14 days, and multivariate statistics
used to identify perturbed pathways. Both metabolomics and transcriptomics
detected changes in the liver which were dose dependent, even after
one day of exposure. Integration of the two datasets associated perturbations
with specific pathways. Hepatic glycogen was decreased due to a decrease
in synthesis, and plasma triglycerides were decreased due to an increase
in fatty acid uptake by the liver. Hepatic succinate was increased
and this was associated with increased heme biosynthesis. Glutathione
synthesis was also increased, presumably in response to oxidative
stress. Liquid Chromatography Mass Spectrometry demonstrated a remodeling
of lipid species, possibly resulting from proliferation of the smooth
endoplasmic reticulum.CONCLUSIONS:The data fusion of metabolomic
and transcriptomic changes proved to be a highly sensitive approach
for monitoring early stage changes in altered hepatic metabolism,
oxidative stress and cytochrome P450 induction simultaneously. This
approach is particularly useful in interpreting changes in metabolites
such as succinate which are hubs of metabolism.},
doi = {10.1186/1471-2164-11-9},
issn = {1471-2164},
pubmedid = {20053287},
url = {http://www.biomedcentral.com/1471-2164/11/9}
}
@ARTICLE{Waters2011a,
author = {Waters, Daniel L. E. and Nock, Catherine J. and Ishikawa, Ryuji and
Rice, Nicole and Henry, Robert J.},
title = {Chloroplast genome sequence confirms distinctness of Australian and
Asian wild rice},
journal = {Ecology and Evolution},
year = {2011},
pages = {no--no},
abstract = {Cultivated rice (Oryza sativa) is an AA genome Oryza species that
was most likely domesticated from wild populations of O. rufipogon
in Asia. O. rufipogon and O. meridionalis are the only AA genome
species found within Australia and occur as widespread populations
across northern Australia. The chloroplast genome sequence of O.
rufipogon from Asia and Australia and O. meridionalis and O. australiensis
(an Australian member of the genus very distant from O. sativa) was
obtained by massively parallel sequencing and compared with the chloroplast
genome sequence of domesticated O. sativa. Oryza australiensis differed
in more than 850 sites single nucleotide polymorphism or indel from
each of the other samples. The other wild rice species had only around
100 differences relative to cultivated rice. The chloroplast genomes
of Australian O. rufipogon and O. meridionalis were closely related
with only 32 differences. The Asian O. rufipogon chloroplast genome
(with only 68 differences) was closer to O. sativa than the Australian
taxa (both with more than 100 differences). The chloroplast sequences
emphasize the genetic distinctness of the Australian populations
and their potential as a source of novel rice germplasm. The Australian
O. rufipogon may be a perennial form of O. meridionalis.},
doi = {10.1002/ece3.66},
issn = {2045-7758},
keywords = {Chloroplast genome, Oryza meridionalis, Oryza rufipogon, Oryza sativa,
wild rice},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1002/ece3.66}
}
@ARTICLE{Waters2011,
author = {Waters, Katrina M. and Jacobs, Jon M. and Gritsenko, Marina A. and
Karin, Norman J.},
title = {Regulation of gene expression and subcellular protein distribution
in MLO-Y4 osteocytic cells by lysophosphatidic acid: Relevance to
dendrite outgrowth},
journal = {Bone},
year = {2011},
volume = {48},
pages = {1328--1335},
number = {6},
month = jun,
abstract = {Osteoblastic and osteocytic cells are highly responsive to the lipid
growth factor lysophosphatidic acid (LPA) but the mechanisms by which
LPA alters bone cell functions are largely unknown. A major effect
of LPA on osteocytic cells is the stimulation of dendrite membrane
outgrowth, a process that we predicted to require changes in gene
expression and protein distribution. We employed DNA microarrays
for global transcriptional profiling of MLO-Y4 osteocytic cells grown
for 6 and 24 h in the presence or absence of LPA. We identified 932
transcripts that displayed statistically significant changes in abundance
of at least 1.25-fold in response to LPA treatment. Gene ontology
(GO) analysis revealed that the regulated gene products were linked
to diverse cellular processes, including DNA repair, response to
unfolded protein, ossification, protein-RNA complex assembly, and
amine biosynthesis. Gene products associated with the regulation
of actin microfilament dynamics displayed the most robust expression
changes, and LPA-induced dendritogenesis in vitro was blocked by
the stress fiber inhibitor cytochalasin D. Mass spectrometry-based
proteomic analysis of MLO-Y4 cells revealed significant LPA-induced
changes in the abundance of 284 proteins at 6 h and 844 proteins
at 24 h. GO analysis of the proteomic data linked the effects of
LPA to cell processes that control of protein distribution and membrane
outgrowth, including protein localization, protein complex assembly,
Golgi vesicle transport, cytoskeleton-dependent transport, and membrane
invagination/endocytosis. Dendrites were isolated from LPA-treated
MLO-Y4 cells and subjected to proteomic analysis to quantitatively
assess the subcellular distribution of proteins. Sets of 129 and
36 proteins were enriched in the dendrite fraction as compared to
whole cells after 6 h and 24 h of LPA exposure, respectively. Protein
markers indicated that membranous organelles were largely excluded
from the dendrites. Highly represented among the proteins with elevated
abundances in dendrites were molecules that regulate cytoskeletal
function, cell motility and membrane adhesion. Our combined transcriptomic/proteomic
analysis of the response of MLO-Y4 osteocytic cells to LPA indicates
that dendritogenesis is a membrane- and cytoskeleton-driven process
with actin dynamics playing a particularly critical role.},
issn = {8756-3282},
keywords = {MLO-Y4 osteocyte-like cells, Lysophosphatidic acid, Gene expression,
Proteomics, Dendrites},
url = {http://www.sciencedirect.com/science/article/pii/S875632821100072X}
}
@ARTICLE{Waters2009,
author = {Waters, Katrina M. and Masiello, Lisa M. and Zangar, Richard C. and
Tarasevich, Barbara J. and Karin, Norman J. and Quesenberry, Ryan
D. and Bandyopadhyay, Somnath and Teeguarden, Justin G. and Pounds,
Joel G. and Thrall, Brian D.},
title = {Macrophage Responses to Silica Nanoparticles are Highly Conserved
Across Particle Sizes},
journal = {Toxicol. Sci.},
year = {2009},
volume = {107},
pages = {553--569},
number = {2},
month = feb,
abstract = {Concerns about the potential adverse health effects of engineered
nanoparticles stems in part from the possibility that some materials
display unique chemical and physical properties at nanoscales which
could exacerbate their biological activity. However, studies that
have assessed the effect of particle size across a comprehensive
set of biological responses have not been reported. Using a macrophage
cell model, we demonstrate that the ability of unopsonized amorphous
silica particles to stimulate inflammatory protein secretion and
induce macrophage cytotoxicity scales closely with the total administered
particle surface area across a wide range of particle diameters (7-500
nm). Whole genome microarray analysis of the early gene expression
changes induced by 10- and 500-nm particles showed that the magnitude
of change for the majority of genes affected correlated more tightly
with particle surface area than either particle mass or number. Gene
expression changes that were particle size-specific were also identified.
However, the overall biological processes represented by all gene
expression changes were nearly identical, irrespective of particle
diameter. Direct comparison of the cell processes represented in
the 10- and 500-nm particle gene sets using gene set enrichment analysis
revealed that among 1009 total biological processes, none were statistically
enriched in one particle size group over the other. The key mechanisms
involved in silica nanoparticle-mediated gene regulation and cytotoxicity
have yet to be established. However, our results suggest that on
an equivalent nominal surface area basis, common biological modes
of action are expected for nano- and supranano-sized silica particles.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/107/2/553}
}
@ARTICLE{Waters2007,
author = {Waters, Katrina M. and Tan, Ruimin and Genetos, Damian C. and Verma,
Seema and Yellowley, Clare E. and Karin, Norman J.},
title = {DNA microarray analysis reveals a role for lysophosphatidic acid
in the regulation of anti-inflammatory genes in MC3T3-E1 cells},
journal = {Bone},
year = {2007},
volume = {41},
pages = {833--841},
number = {5},
month = nov,
abstract = {Lysophosphatidic acid (LPA) is a bioactive lipid with functional properties
that overlap those of growth factors and cytokines. LPA production
in vivo is linked to platelet degranulation and the biological activities
of this lipid are associated with wound healing. Osteoblasts and
their progenitor cells are exposed to high levels of this lipid factor
in regions adjacent to bone fractures and we postulate a role for
LPA in skeletal healing. The regeneration of bone injuries requires
a complex array of changes in gene expression, but the effects of
LPA on mRNA levels in bone cells have not been investigated. We performed
a genome-wide expression analysis in LPA-treated MC3T3-E1 pre-osteoblastic
cells using Affymetrix GeneChip arrays. Cells exposed to LPA for
6 h exhibited 513 regulated genes, whereas changes in the levels
of 54 transcripts were detected after a 24-h LPA treatment. Gene
ontology analysis linked LPA-regulated gene products to biological
processes that are known to govern bone healing, including cell proliferation,
response to stress, organ development, chemotaxis/motility, and response
to stimuli. Among the gene products most highly up-regulated by LPA
were transcripts encoding the anti-inflammatory proteins sST2, ST2L,
and heat-shock protein 25 (HSP25). RT-PCR analysis confirmed that
these mRNAs were increased significantly in MC3T3-E1 cells and primary
osteoblasts exposed to LPA. The response of cells to LPA is mediated
by G-protein-coupled receptors, and the stimulation of anti-inflammatory
gene expression in MC3T3-E1 cells was blocked by Ki16425, an inhibitor
of LPA1 and LPA3 receptor forms. Pertussis toxin impaired only the
LPA-induced expression of sST2. LPA-stimulated levels of sST2, ST2L
and HSP25 mRNAs persisted if the cytosolic Ca2+ elevations elicited
by this lipid were blocked with BAPTA. In contrast to the stimulatory
effect of LPA, exposure of MC3T3-E1 cells to fluid shear reduced
the transcript levels of all three anti-inflammatory genes. The induction
of sST2, ST2L and HSP25 expression by LPA suggests a role for this
lipid factor in the regulation of osteoblastic cell function during
periods of inflammation.},
issn = {8756-3282},
keywords = {Lysophosphatidic acid, Osteoblast, Gene expression, DNA microarray,
Inflammation},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4PB0PP5-3/2/3c1640012ecbb554230095b9d272665c}
}
@ARTICLE{Waters2009a,
author = {Waters, Katrina M. and Tan, Ruimin and Opresko, Lee K. and Quesenberry,
Ryan D. and Bandyopadhyay, Somnath and Chrisler, William B. and Weber,
Thomas J.},
title = {Cellular dichotomy between anchorage-independent growth responses
to bFGF and TPA reflects molecular switch in commitment to carcinogenesis},
journal = {Mol. Carcinog.},
year = {2009},
volume = {48},
pages = {1059--1069},
number = {11},
abstract = {Abstract 10.1002/mc.20558.abs We have investigated gene expression
patterns underlying reversible and irreversible anchorage-independent
growth (AIG) phenotypes to identify more sensitive markers of cell
transformation for studies directed at interrogating carcinogenesis
responses. In JB6 mouse epidermal cells, basic fibroblast growth
factor (bFGF) induces an unusually efficient and reversible AIG response,
relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG
which is irreversible. The reversible and irreversible AIG phenotypes
are characterized by largely nonoverlapping global gene expression
profiles. However, a subset of differentially expressed genes were
identified as common to reversible and irreversible AIG phenotypes,
including genes regulated in a reciprocal fashion. Hepatic leukemia
factor (HLF) and D-site albumin promoter-binding protein (DBP) were
increased in both bFGF and TPA soft agar colonies and selected for
functional validation. Ectopic expression of human HLF and DBP in
JB6 cells resulted in a marked increase in TPA- and bFGF-regulated
AIG responses. HLF and DBP expression were increased in soft agar
colonies arising from JB6 cells exposed to gamma radiation and in
a human basal cell carcinoma tumor tissue, relative to paired nontumor
tissue. Subsequent biological network analysis suggests that many
of the differentially expressed genes that are common to bFGF- and
TPA-dependent AIG are regulated by c-Myc, SP-1, and HNF-4 transcription
factors. Collectively, we have identified a potential molecular switch
that mediates the transition from reversible to irreversible AIG.
© 2009 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {anchorage-independent growth, reversible, hepatic leukemia factor},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20558}
}
@ARTICLE{Waters2009b,
author = {Waters, S. M. and Kelly, J. P. and O'Boyle, P. and Moloney, A. P.
and Kenny, D. A.},
title = {Effect of level and duration of dietary n-3 polyunsaturated fatty
acid supplementation on the transcriptional regulation of {Delta}9-desaturase
in muscle of beef cattle},
journal = {J Anim Sci},
year = {2009},
volume = {87},
pages = {244--252},
number = {1},
month = jan,
abstract = {The objective of this study was to examine the effect of level and
duration of feeding of an n-3 PUFA-enriched fish oil (FO) supplement
in combination with soybean oil (SO) on the transcriptional regulation
of {Delta}9-desaturase gene expression in bovine muscle. Beef bulls
(n = 40) were assigned to 1 of 4 iso-lipid and isonitrogenous concentrate
diets fed for ad libitum intake for a 100-d finishing period. Concentrates
were supplemented with one of the following: 1) 6% SO (CON); 2) 6%
SO + 1% FO (FO1); 3) 6% SO + 2% FO (FO2); or 4) 8% palmitic acid
for the first 50 d and 6% SO + 2% FO for the second 50 d [FO2(50)].
Samples of LM were harvested and concentrations of fatty acids were
measured. Total RNA was isolated and the gene expression of {Delta}9-desaturase
was determined. The mRNA expression of putative regulators of {Delta}9-desaturase
gene expression, sterol regulatory element binding protein-1c (SREBP-1c)
and peroxisome proliferator activated receptor-{alpha} (PPAR-{alpha}),
were also measured in the CON and FO2 groups. Expression of mRNA
for {Delta}9-desaturase was decreased (P < 0.05) 2.6-, 4.4-, and
4.9-fold in FO1, FO2(50), and FO2 compared with CON, respectively.
Expression of {Delta}9-desaturase mRNA tended to be reduced (P =
0.09) by increasing FO from 1 to 2%, but was not affected by duration
of supplementation (P > 0.24). Expression of mRNA for SREBP-1c was
decreased 2-fold in FO2 compared with CON (P < 0.05), whereas expression
of PPAR-{alpha} was not affected (P > 0.30). There was a positive
relationship between {Delta}9-desaturase and SREBP-1c gene expression
(P < 0.01), but the expression of both genes was negatively related
to tissue concentrations of n-3 PUFA (P < 0.05) and positively related
to concentration of n-6 PUFA (P < 0.01). Simultaneous enhancement
of tissue concentrations of CLA and n-3 PUFA concentrations in bovine
muscle may be hindered by negative interactions between n-3 PUFA
and {Delta}9-desaturase gene expression, possibly mediated through
reduced expression of SREBP-1c.},
url = {http://jas.fass.org/cgi/content/abstract/87/1/244}
}
@ARTICLE{Wathes2009,
author = {Wathes, D. Claire and Cheng, Zhangrui and Chowdhury, Waliul and Fenwick,
Mark A. and Fitzpatrick, Richard and Morris, Dermot G. and Patton,
Joe and Murphy, John J.},
title = {Negative energy balance alters global gene expression and immune
responses in the uterus of postpartum dairy cows},
journal = {Physiol Genomics},
year = {2009},
volume = {39},
pages = {1--13},
number = {1},
month = sep,
abstract = {Most dairy cows suffer uterine microbial contamination postpartum.
Persistent endometritis often develops, associated with reduced fertility.
We used a model of differential feeding and milking regimes to produce
cows in differing negative energy balance status in early lactation
(mild or severe, MNEB or SNEB). Blood hematology was assessed preslaughter
at 2 wk postpartum. RNA expression in endometrial samples was compared
using bovine Affymetrix arrays. Data were mapped using Ingenuity
Pathway Analysis. Circulating concentrations of IGF-I remained lower
in the SNEB group, whereas blood nonesterified fatty acid and {beta}-hydroxybutyrate
concentrations were raised. White blood cell count and lymphocyte
number were reduced in SNEB cows. Array analysis of endometrial samples
identified 274 differentially expressed probes representing 197 recognized
genes between the energy balance groups. The main canonical pathways
affected related to immunological and inflammatory disease and connective
tissue disorders. Inflammatory response genes with major upregulation
in SNEB cows included matrix metalloproteinases, chemokines, cytokines,
and calgranulins. Expression of several interferon-inducible genes
including ISG20, IFIH1, MX1, and MX2 were also significantly increased
in the SNEB cows. These results provide evidence that cows in SNEB
were still undergoing an active uterine inflammatory response 2 wk
postpartum, whereas MNEB cows had more fully recovered from their
energy deficit, with their endometrium reaching a more advanced stage
of repair. SNEB may therefore prevent cows from mounting an effective
immune response to the microbial challenge experienced after calving,
prolonging the time required for uterine recovery and compromising
subsequent fertility.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/39/1/1}
}
@ARTICLE{Watkins2009,
author = {Watkins, C. A. And Mackellar, A. And Frew, D. And Mackie, C. And
George, A. And Hopkins, J. And Burgess, S. T. G. And Mcneilly, T.
N. And Huntley, J. F.},
title = {Gene expression profiling of ovine keratinocytes stimulated with
Psoroptes ovis mite antigen – a preliminary study},
journal = {Parasite Immunology},
year = {2009},
volume = {31},
pages = {304--311},
number = {6},
abstract = {SUMMARY Sheep scab is caused by the noninvasive mite, Psoroptes ovis,
which initiates a profound pro-inflammatory skin response leading
to lesion development. To investigate these early events between
the skin and the parasite, primary ovine epidermal keratinocyte cultures
were generated and challenged with mite derived antigens. The kinetics
of the mRNA response of these cells were monitored by microarray.
The results indicated that the cells responded within 1Â h of challenge,
with a significant increase in the pro-inflammatory cytokine IL-8.
This result was confirmed by real-time RT-PCR, and showed that IL-8
up-regulation was maximal at 1Â h but declined to pre-stimulation
levels at 24 and 48Â h. The IL-8 mRNA response to mite wash antigens
containing secretory and/or excretory proteins was also investigated
and compared to the response to whole mite antigen. These studies
revealed that the mite wash antigen, at a challenge dose of 10 µg/mL,
was markedly more potent and induced significantly higher levels
of IL-8 mRNA than the same concentration of whole mite antigen. These
results are discussed in relation to mite establishment and survival
on the ovine host.},
issn = {1365-3024},
keywords = {Psoroptes ovis, sheep scab, gene expression, primary keratinocyte
culture, interleukin-8},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3024.2009.01103.x}
}
@ARTICLE{Watkins2009a,
author = {Watkins, Nicholas A. and Gusnanto, Arief and de Bono, Bernard and
De, Subhajyoti and Miranda-Saavedra, Diego and Hardie, Debbie L.
and Angenent, Will G. J. and Attwood, Antony P. and Ellis, Peter
D. and Erber, Wendy and Foad, Nicola S. and Garner, Stephen F. and
Isacke, Clare M. and Jolley, Jennifer and Koch, Kerstin and Macaulay,
Iain C. and Morley, Sarah L. and Rendon, Augusto and Rice, Kate M.
and Taylor, Niall and Thijssen-Timmer, Daphne C. and Tijssen, Marloes
R. and van der Schoot, C. Ellen and Wernisch, Lorenz and Winzer,
Thilo and Dudbridge, Frank and Buckley, Christopher D. and Langford,
Cordelia F. and Teichmann, Sarah and Gottgens, Berthold and Ouwehand,
Willem H. and on behalf of the Bloodomics Consortium},
title = {A HaemAtlas: characterizing gene expression in differentiated human
blood cells},
journal = {Blood},
year = {2009},
volume = {113},
pages = {e1--9},
number = {19},
month = may,
abstract = {Hematopoiesis is a carefully controlled process that is regulated
by complex networks of transcription factors that are, in part, controlled
by signals resulting from ligand binding to cell-surface receptors.
To further understand hematopoiesis, we have compared gene expression
profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic
and helper T cells, natural killer cells, granulocytes, and monocytes
using whole genome microarrays. A bioinformatics analysis of these
data was performed focusing on transcription factors, immunoglobulin
superfamily members, and lineage-specific transcripts. We observed
that the numbers of lineage-specific genes varies by 2 orders of
magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes.
In addition, we have identified novel coexpression patterns for key
transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and
GATA2-KLF1). This study represents the most comprehensive analysis
of gene expression in hematopoietic cells to date and has identified
genes that play key roles in lineage commitment and cell function.
The data, which are freely accessible, will be invaluable for future
studies on hematopoiesis and the role of specific genes and will
also aid the understanding of the recent genome-wide association
studies.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/19/e1}
}
@ARTICLE{Watson2004,
author = {Watson, J.E. Vivienne and Kamkar, Shervin and James, Karen and Kowbel,
David and Andaya, Armann and Paris, Pamela L. and Simko, Jeffry and
Carroll, Peter and McAlhany, Stephanie and Rowley, David and Collins,
Colin},
title = {Molecular analysis of WFDC1/ps20 gene in prostate cancer},
journal = {Prostate},
year = {2004},
volume = {61},
pages = {192--199},
number = {2},
abstract = {Abstract 10.1002/pros.20100.abs BACKGROUND WFDC1/ps20 protein has
been previously established as a growth suppressor of the prostate
cancer cell line PC3. It maps to chromosome 16q23.1, a region of
frequent loss of heterozygosity, familial association, and genomic
loss in prostate cancer. We, therefore, chose to examine WFDC1/ps20
for mutations and expression changes in prostate cancer. METHODS
DNA from 21 prostate cancer patients and 5 prostate cancer cell lines
was screened for mutations in the WFDC1/ps20 gene by sequencing PCR
products of each exon. An SphI polymorphism in the 5′ UTR was screened
in 23 tumors, 22 normal adjacent prostate tissue samples, and 35
control DNAs. Expression of WFDC1/ps20 in different tissue types
was examined by Northern blot and by PCR across a multi-tissue cDNA
panel. Expression patterns of WFDC1/ps20 in primary tumors were examined
by full-length RT-PCR and products were cloned and sequenced to identify
novel splice forms. Quantitative RT-PCR analysis of WFDC1/ps20 was
performed in a separate cohort of matched tumor/benign tissues. RESULTS
No tumor-associated mutations were identified in the coding region
of WFDC1/ps20. A novel polymorphism was found in exon 6 in DNA from
cell lines, tumors, and normal adjacent benign tissue. A novel splice
form completely deleted for exon 3 was found in tumor and normal
prostate RNA. Quantitative RT-PCR demonstrated significant down regulation
of WFDC1/ps20 in prostate tumors. Subdivision of normal tissue into
stromal and epithelial compartments showed that WFDC1/ps20 expression
correlates exponentially with the amount of stroma present. CONCLUSIONS
WFDC1/ps20 is down regulated but not frequently mutated in prostate
cancer. It is expressed predominantly in the normal stroma of the
prostate. We, therefore, propose that WFDC1/ps20 may not be a classical
tumor suppressor gene, but might play a role in the maintenance of
the normal extra cellular matrix milieu in the prostate. © 2004
Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {WFDC1, ps20, 16q23.1, prostate cancer, stroma},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20100}
}
@ARTICLE{Watson2002,
author = {Watson, Mark A. and Gutmann, David H. and Peterson, Kelly and Chicoine,
Michael R. and Kleinschmidt-DeMasters, Bette K. and Brown, Henry
G. and Perry, Arie},
title = {Molecular Characterization of Human Meningiomas by Gene Expression
Profiling Using High-Density Oligonucleotide Microarrays},
journal = {Am. J. Pathol.},
year = {2002},
volume = {161},
pages = {665--672},
number = {2},
month = aug,
abstract = {Meningiomas are common central nervous system neoplasms that exhibit
remarkably diverse histopathology and biological behavior. Compared
to astrocytomas, the most common central nervous system tumor, little
is known about the molecular pathways critical for meningioma tumor
formation and malignant progression. As an initial step toward characterizing
the genetic basis of meningioma pathogenesis, we assessed cancer-related
gene expression profiles of nonneoplastic leptomeningeal specimens
and human meningiomas of varying World Health Organization (WHO)
grade using high-density oligonucleotide microarrays. Although expression
profile differences between nonneoplastic and meningioma specimens
were readily discernible, the expression profile of a subset of genes
could also distinguish WHO grade I from WHO grades II and III tumors.
Altered expression levels of several genes identified in this study
have been previously noted in meningiomas (eg, growth hormone receptor,
IGFBP-7, endothelin receptor A, IGF2). However, we also identified
a number of novel genes whose expression was associated with WHO
grade and was confirmed by reverse transcriptase-polymerase chain
reaction in a larger, independent set of meningeal tumors (n = 47).
This report represents the first gene expression profiling studies
of meningiomas and identifies some initial candidate genes that may
provide further insights into the genetic basis for meningioma pathogenesis.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/161/2/665}
}
@ARTICLE{Watson2007,
author = {Watson, Mark A. and Ylagan, Lourdes R. and Trinkaus, Kathryn M. and
Gillanders, William E. and Naughton, Michael J. and Weilbaecher,
Katherine N. and Fleming, Timothy P. and Aft, Rebecca L.},
title = {Isolation and Molecular Profiling of Bone Marrow Micrometastases
Identifies TWIST1 as a Marker of Early Tumor Relapse in Breast Cancer
Patients},
journal = {Clin. Cancer Res.},
year = {2007},
volume = {13},
pages = {5001--5009},
number = {17},
month = sep,
abstract = {Purpose: Micrometastatic cells detected in the bone marrow have prognostic
significance in breast cancer. These cells are heterogeneous and
likely do not exhibit uniform biological behavior. To understand
the molecular diversity of disseminated cancer cells that reside
in bone marrow, we enriched this cell population and did global gene
expression profiling in the context of a prospective clinical trial
involving women with clinical stage II/III breast cancer undergoing
neoadjuvant chemotherapy. Experimental Design: Enrichment of TACSTD1
(EpCAM)-expressing cells from bone marrow of breast cancer patients
was achieved using immunomagnetic beads. Gene expression profiles
were compared between enriched cell populations and whole bone marrow
from 5 normal volunteers and 23 breast cancer patients after neoadjuvant
chemotherapy treatment. Enriched cells from bone marrow samples of
breast cancer patients before treatment or at 1 year follow-up were
also analyzed (total of 87 data sets). The expression of transcripts
specifically detected in enriched cell populations from breast cancer
patients was correlated with 1-year clinical outcome using quantitative
reverse transcription-PCR in an independent cohort of bone marrow
samples. Results: Analysis of EpCAM-enriched bone marrow cells revealed
specific expression of a subgroup of transcripts, including the metastasis
regulator, TWIST1. Most transcripts identified, including TWIST1,
were not expressed in enriched populations of bone marrow from normal
volunteers, suggesting that this expression profile reflects a signature
of breast cancer bone marrow micrometastases that persist after chemotherapy.
In an independent set of bone marrow samples obtained before any
treatment, TWIST1 expression correlated with early disease relapse.
Conclusions: Disseminated breast cancer cells present in bone marrow
after chemotherapy possess unique transcriptional signatures. Genes
whose expression is overrepresented in these cell populations, such
as TWIST1, may prove to be excellent markers of early distant relapse
in breast cancer patients.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/13/17/5001}
}
@ARTICLE{Watson2006,
author = {Watson, M. and Drew and Lind, M. and Cawkwell, L.},
title = {Expression microarray analysis of newly-developed chemotherapy-resistant
breast cancer cell lines},
journal = {European Journal of Cancer Supplements},
year = {2006},
volume = {4},
pages = {138--138},
number = {2},
month = mar,
issn = {1359-6349},
url = {http://www.sciencedirect.com/science/article/B75GT-4JWWWXS-CJ/2/1f0f4be52054f81902225ef9f96cd7ec}
}
@ARTICLE{Watson2009,
author = {Watson, Spencer K. and Woolcock, Bruce W. and Fee, John N. and Bainbridge,
Terry C. and Webber, Douglas and Kinahan, Thomas J. and Lam, Wan
L. and Vielkind, Juergen R.},
title = {Minimum altered regions in early prostate cancer progression identified
by high resolution whole genome tiling path BAC array comparative
hybridization},
journal = {Prostate},
year = {2009},
volume = {69},
pages = {961--975},
number = {9},
abstract = {Abstract 10.1002/pros.20949.abs BACKGROUND Carcinoma of the prostate
(CaP) is a serious health problem. The altered molecular mechanisms
that lead to this disease are poorly understood. METHODS Specimens
from radical prostatectomies and blood were collected from 18 CaP
surgery patients. For CGH studies, 20 CaP-related samples (16 Gleason
grade 3, 3 higher grades, 1 BPH sample) and 18 samples of patient-matched
normal epithelial cells were obtained by laser-assisted microdissection
from frozen sections of the 18 prostatectomy specimens. High resolution
SMRT aCGH was used to compare genomic profiles of prostatic samples
to patient-matched blood and pooled female DNA. TMPRSS2-ERG fusion
transcript analysis was performed by RT-PCR in relation to alterations
detected at the TMPRSS2 locus. RESULTS Our comprehensive aCGH approach
allowed us to define 35 regions of recurrent alterations while excluding
germline copy number polymorphisms. Novel regions identified include
2q14.2, containing INHBB, and 17q21.31. The TMPRSS2 locus at 21q22.3
may be a hotspot for rearrangements with 75% of the alterations resulting
in the expression of a TMPRSS2-ERG fusion transcript. Differences
in fusion expression in different areas in an individual tumor focus
and expression in adjacent normal epithelium supported intrafocal
heterogeneity and field cancerization, respectively. Both features
challenge our efforts to develop more objective markers for diagnosis
and prediction of the severity of CaP. CONCLUSION The high-density
array enabled precise mapping of genomic alterations and consequently
definition of minimum altered regions smaller than previously reported
thus facilitating identification of those genes that contribute to
the cancer transformation process. Prostate 69: 961–975, 2009.
© 2009 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {Gleason grade, laser-assisted microdissection, whole-genome tiling
path BAC array, high resolution aCGH, minimum altered genomic regions,
TMPRSS2-ERG, INHBB, intrafocal heterogeneity},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20949}
}
@ARTICLE{Wauthier2010,
author = {Wauthier, Valerie and Sugathan, Aarathi and Meyer, Rosana D. and
Dombkowski, Alan A. and Waxman, David J.},
title = {Intrinsic Sex Differences in the Early Growth Hormone Responsiveness
of Sex-Specific Genes in Mouse Liver},
journal = {Mol. Endocrinol.},
year = {2010},
volume = {24},
pages = {667--678},
number = {3},
month = mar,
abstract = {Sex differences in liver gene expression are dictated by sex differences
in circulating GH profiles. Presently, the pituitary hormone dependence
of mouse liver gene expression was investigated on a global scale
to discover sex-specific early GH response genes that could contribute
to sex-specific regulation of downstream GH targets and to ascertain
whether intrinsic sex differences characterize hepatic responses
to plasma GH stimulation. Global RNA expression analysis identified
two distinct classes of sex-specific mouse liver genes: genes subject
to positive regulation (class I) and genes subject to negative regulation
by pituitary hormones (class II). Genes activated or repressed in
hypophysectomized (Hypox) mouse liver within 30-90 min of GH pulse
treatment at a physiological dose were identified as putative direct
targets of GH action (early response genes). Intrinsic sex differences
in the GH responsiveness of a subset of these early response genes
were observed. Notably, 45 male-specific genes, including five encoding
transcriptional regulators that may mediate downstream sex-specific
transcriptional responses, were induced by GH within 30 min in Hypox
male but not Hypox female mouse liver. The early GH response genes
were enriched in 29 male-specific targets of the transcription factor
myocyte enhancer factor 2, whose activation in hepatic stellate cells
is associated with liver fibrosis leading to hepatocellular carcinoma,
a male-predominant disease. Thus, the rapid activation by GH pulses
of certain sex-specific genes is modulated by intrinsic sex-specific
factors, which may be associated with prior hormone exposure (epigenetic
mechanisms) or genetic factors that are pituitary-independent, and
could contribute to sex differences in predisposition to liver cancer
or other hepatic pathophysiologies.},
url = {http://mend.endojournals.org/cgi/content/abstract/24/3/667}
}
@ARTICLE{Wauthier2008,
author = {Wauthier, Valerie and Waxman, David J.},
title = {Sex-Specific Early Growth Hormone Response Genes in Rat Liver},
journal = {Mol. Endocrinol.},
year = {2008},
volume = {22},
pages = {1962--1974},
number = {8},
month = aug,
abstract = {Pituitary GH-secretory profiles are sex dependent and regulate the
sexually dimorphic expression of a large number of genes in the liver.
The slow response of many sex-specific liver genes to changes in
plasma GH status suggests that GH acts in the liver via both direct
and indirect mechanisms organized in a hierarchical regulatory network.
Presently, genome-wide liver transcription profiling was conducted
to elucidate the global impact of pituitary hormone ablation on the
sex specificity of rat liver gene expression and to identify sex-specific
genes that respond rapidly to GH as candidates for direct targets
of GH action. Hypophysectomy abolished the sex specificity of approximately
90% of 1032 sex-dependent genes, consistent with the dominant role
of pituitary GH in regulating liver sexual dimorphism. Two major
classes of sex-specific genes were identified: genes that were down-regulated
after hypophysectomy and may be subject to positive GH regulation
(461 class I genes), and genes that were up-regulated after hypophysectomy
and may be subject to negative GH regulation (224 class II genes).
Fifty class I sex-specific genes were induced, and 38 class II sex-specific
genes were suppressed within 90 min of a physiological GH pulse,
suggesting they are primary GH response genes. A further 71 sex-specific
genes responded after a second GH treatment and may correspond to
secondary response genes. Twenty four DNA-binding proteins were identified
as early GH response genes, of which 15 were induced and nine were
suppressed by GH. Five of these 24 genes displayed sex-specific expression,
consistent with a hierarchical transcriptional network controlling
sex-specific liver gene expression. Class II male-specific genes,
such as Cyp2a2 and Cyp2c13, were down-regulated within 30 min of
GH pulse treatment, as determined by heterogeneous nuclear RNA analysis,
suggesting that transcription of these genes is restricted to the
GH-free interpulse period in adult male rat liver. We conclude that
GH acts via both positive and negative regulatory mechanisms to establish
and maintain the sex specificity of liver gene expression.},
url = {http://mend.endojournals.org/cgi/content/abstract/22/8/1962}
}
@ARTICLE{Waveren2006,
author = {van Waveren, Corina and Sun, Yubo and Cheung, Herman S. and Moraes,
Carlos T.},
title = {Oxidative phosphorylation dysfunction modulates expression of extracellular
matrix--remodeling genes and invasion},
journal = {Carcinogenesis},
year = {2006},
volume = {27},
pages = {409--418},
number = {3},
month = mar,
abstract = {A number of recent studies suggest that mitochondrial function is
a player in tumor development and progression. In this study, we
have used gene expression arrays to examine transcriptional differences
between oxidative phosphorylation (OXPHOS)-competent and OXPHOS-impaired
human osteosarcoma cells. Genes associated with extracellular matrix
remodeling, including members of the matrix metalloproteinases (MMPs)
and tissue inhibitors of the MMP (TIMP) family, urokinase plasminogen
activator and its inhibitor plasminogen-activator inhibitor-1 (PAI1),
and CTGF and CYR61 (members of the Cysteine-rich 61, Connective Tissue
Growth Factor and Nephroblastoma-overexpressed (CCN) gene family
of growth regulators), were among the ones significantly altered
in the OXPHOS-deficient cells. These changes were confirmed by RT-PCR
and promoter reporter assays. Alterations at the protein level for
some of these factors were also observed, though at a lower magnitude,
with the exception of TIMP1, where a marked change in steady-state
levels of the protein was observed after induction of OXPHOS dysfunction.
Repopulation of mitochondrial DNA (mtDNA)-less cells with wild-type
mtDNA reduced matrigel invasion, whereas repopulation with a mutated
mtDNA did not. Taken together our data suggests that OXPHOS dysfunction
modulates the invasive phenotype by transcriptional regulation of
genes coding for members of the MMP/TIMP system, urokinase plasminogen
activator/plasminogen-activator inhibitor I and CCN proteins.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/27/3/409}
}
@ARTICLE{Wayne2007,
author = {Wayne, Marta L. and Telonis-Scott, Marina and Bono, Lisa M. and Harshman,
Larry and Kopp, Artyom and Nuzhdin, Sergey V. and McIntyre, Lauren
M.},
title = {Simpler mode of inheritance of transcriptional variation in male
Drosophila melanogaster},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {18577--18582},
number = {47},
month = nov,
abstract = {Sexual selection drives faster evolution in males. The X chromosome
is potentially an important target for sexual selection, because
hemizygosity in males permits accumulation of alleles, causing tradeoffs
in fitness between sexes. Hemizygosity of the X could cause fundamentally
different modes of inheritance between the sexes, with more additive
variation in males and more nonadditive variation in females. Indeed,
we find that genetic variation for the transcriptome is primarily
additive in males but nonadditive in females. As expected, these
differences are more pronounced on the X chromosome than the autosomes,
but autosomal loci are also affected, possibly because of X-linked
transcription factors. These differences may be of evolutionary significance
because additive variation responds quickly to selection, whereas
nonadditive genetic variation does not. Thus, hemizygosity of the
X may underlie much of the faster male evolution of the transcriptome
and potentially other phenotypes. Consistent with this prediction,
genes that are additive in males and nonadditive in females are overrepresented
among genes responding to selection for increased mating speed.},
url = {http://www.pnas.org/cgi/content/abstract/104/47/18577}
}
@ARTICLE{Weatherbee2006,
author = {Weatherbee, Scott D. and Anderson, Kathryn V. and Niswander, Lee
A.},
title = {LDL-receptor-related protein 4 is crucial for formation of the neuromuscular
junction},
journal = {Development},
year = {2006},
volume = {133},
pages = {4993--5000},
number = {24},
month = dec,
abstract = {Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member
of a family of structurally related, single-pass transmembrane proteins
that carry out a variety of functions in development and physiology,
including signal transduction and receptor-mediated endocytosis.
Lrp4 is expressed in multiple tissues in the mouse, and is important
for the proper development and morphogenesis of limbs, ectodermal
organs, lungs and kidneys. We show that Lrp4 is also expressed in
the post-synaptic endplate region of muscles and is required to form
neuromuscular synapses. Lrp4-mutant mice die at birth with defects
in both presynaptic and postsynaptic differentiation, including aberrant
motor axon growth and branching, a lack of acetylcholine receptor
and postsynaptic protein clustering, and a failure to express postsynaptic
genes selectively by myofiber synaptic nuclei. Our data show that
Lrp4 is required during the earliest events in postsynaptic neuromuscular
junction (NMJ) formation and suggest that it acts in the early, nerveindependent
steps of NMJ assembly. The identification of Lrp4 as a crucial factor
for NMJ formation may have implications for human neuromuscular diseases
such as myasthenia syndromes.},
url = {http://dev.biologists.org/cgi/content/abstract/133/24/4993}
}
@ARTICLE{Weaver2005,
author = {Weaver, Ian C. G. and Champagne, Frances A. and Brown, Shelley E.
and Dymov, Sergiy and Sharma, Shakti and Meaney, Michael J. and Szyf,
Moshe},
title = {Reversal of Maternal Programming of Stress Responses in Adult Offspring
through Methyl Supplementation: Altering Epigenetic Marking Later
in Life},
journal = {J. Neurosci.},
year = {2005},
volume = {25},
pages = {11045--11054},
number = {47},
month = nov,
abstract = {Stress responses in the adult rat are programmed early in life by
maternal care and associated with epigenomic marking of the hippocampal
exon 17 glucocorticoid receptor (GR) promoter. To examine whether
such epigenetic programming is reversible in adult life, we centrally
infused the adult offspring with the essential amino acid L-methionine,
a precursor to S-adenosyl-methionine that serves as the donor of
methyl groups for DNA methylation. Here we report that methionine
infusion reverses the effect of maternal behavior on DNA methylation,
nerve growth factor-inducible protein-A binding to the exon 17 promoter,
GR expression, and hypothalamic-pituitary-adrenal and behavioral
responses to stress, suggesting a causal relationship among epigenomic
state, GR expression, and stress responses in the adult offspring.
These results demonstrate that, despite the inherent stability of
the epigenomic marks established early in life through behavioral
programming, they are potentially reversible in the adult brain.},
url = {http://www.jneurosci.org/cgi/content/abstract/25/47/11045}
}
@ARTICLE{Weaver2007,
author = {Weaver, Ian C. G. and D'Alessio, Ana C. and Brown, Shelley E. and
Hellstrom, Ian C. and Dymov, Sergiy and Sharma, Shakti and Szyf,
Moshe and Meaney, Michael J.},
title = {The Transcription Factor Nerve Growth Factor-Inducible Protein A
Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early
Genes},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {1756--1768},
number = {7},
month = feb,
abstract = {Maternal care alters epigenetic programming of glucocorticoid receptor
(GR) gene expression in the hippocampus, and increased postnatal
maternal licking/grooming (LG) behavior enhances nerve growth factor-inducible
protein A (NGFI-A) transcription factor binding to the exon 17 GR
promoter within the hippocampus of the offspring. We tested the hypothesis
that NGFI-A binding to the exon 17 GR promoter sequence marks this
sequence for histone acetylation and DNA demethylation and that such
epigenetic alterations subsequently influence NGFI-A binding and
GR transcription. We report that (1) NGFI-A binding to its consensus
sequence is inhibited by DNA methylation, (2) NGFI-A induces the
activity of exon 17 GR promoter in a transient reporter assay, (3)
DNA methylation inhibits exon 17 GR promoter activity, and (4) whereas
NGFI-A interaction with the methylated exon 17 GR promoter is reduced,
NGFI-A overexpression induces histone acetylation, DNA demethylation,
and activation of the exon 17 GR promoter in transient transfection
assays. Site-directed mutagenesis assays demonstrate that NGFI-A
binding to the exon 17 GR promoter is required for such epigenetic
reprogramming. In vivo, enhanced maternal LG is associated with increased
NGFI-A binding to the exon 17 GR promoter in the hippocampus of pups,
and NGFI-A-bound exon 17 GR promoter is unmethylated compared with
unbound exon 17 GR promoter. Knockdown experiments of NGFI-A in hippocampal
primary cell culture show that NGFI-A is required for serotonin-induced
DNA demethylation and increased exon 17 GR promoter expression. The
data are consistent with the hypothesis that NGFI-A participates
in epigenetic programming of GR expression.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/7/1756}
}
@ARTICLE{Weaver2006,
author = {Weaver, Ian C. G. and Meaney, Michael J. and Szyf, Moshe},
title = {Maternal care effects on the hippocampal transcriptome and anxiety-mediated
behaviors in the offspring that are reversible in adulthood},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {3480--3485},
number = {9},
month = feb,
abstract = {Early-life experience has long-term consequences on behavior and stress
responsivity of the adult. We previously proposed that early-life
experience results in stable epigenetic programming of glucocorticoid
receptor gene expression in the hippocampus. The aim of this study
was to examine the global effect of early-life experience on the
hippocampal transcriptome and the development of stress-mediated
behaviors in the offspring and whether such effects were reversible
in adulthood. Adult offspring were centrally infused with saline
vehicle, the histone deacetylase inhibitor trichostatin A (TSA),
or the essential amino acid L-methionine. The animals were assessed
in an unfamiliar open-field arena, and the hippocampal transcriptome
of each animal was evaluated by microarray analysis. Here we report
that TSA and methionine treatment reversed the effect of maternal
care on open-field behavior. We identified >900 genes stably regulated
by maternal care. A fraction of these differences in gene expression
is reversible by either the histone deacetylase inhibitor TSA or
the methyl donor L-methionine. These results suggest that early-life
experience has a stable and broad effect on the hippocampal transcriptome
and anxiety-mediated behavior, which is potentially reversible in
adulthood.},
url = {http://www.pnas.org/cgi/content/abstract/103/9/3480}
}
@ARTICLE{Webb2009,
author = {Webb, Katharine and Norton, William and Trümbach, Dietrich and Meijer,
Annemarie and Ninkovic, Jovica and Topp, Stefanie and Heck, Daniel
and Marr, Carsten and Wurst, Wolfgang and Theis, Fabian and Spaink,
Herman and Bally-Cuif, Laure},
title = {Zebrafish reward mutants reveal novel transcripts mediating the behavioral
effects of amphetamine},
journal = {Genome Biology},
year = {2009},
volume = {10},
pages = {R81},
number = {7},
abstract = {BACKGROUND:Addiction is a pathological dysregulation of the brain's
reward systems, determined by several complex genetic pathways. The
conditioned place preference test provides an evaluation of the effects
of drugs in animal models, allowing the investigation of substances
at a biologically relevant level with respect to reward. Our lab
has previously reported the development of a reliable conditioned
place preference paradigm for zebrafish. Here, this test was used
to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant,
no addiction (naddne3256), which fails to respond to amphetamine,
and which we used as an entry point towards identifying the behaviorally
relevant transcriptional response to amphetamine.RESULTS:Through
the combination of microarray experiments comparing the adult brain
transcriptome of mutant and wild-type siblings under normal conditions,
as well as their response to amphetamine, we identified genes that
correlate with the mutants' altered conditioned place preference
behavior. In addition to pathways classically involved in reward,
this gene set shows a striking enrichment in transcription factor-encoding
genes classically involved in brain development, which later appear
to be re-used within the adult brain. We selected a subset of them
for validation by quantitative PCR and in situ hybridization, revealing
that specific brain areas responding to the drug through these transcription
factors include domains of ongoing adult neurogenesis. Finally, network
construction revealed functional connections between several of these
genes.CONCLUSIONS:Together, our results identify a new network of
coordinated gene regulation that influences or accompanies amphetamine-triggered
conditioned place preference behavior and that may underlie the susceptibility
to addiction.},
doi = {10.1186/gb-2009-10-7-r81},
issn = {1465-6906},
pubmedid = {19646228},
url = {http://genomebiology.com/2009/10/7/R81}
}
@ARTICLE{Webb2009a,
author = {Webb, R.N. and Cruse, J.M. and Lewis, R.E.},
title = {Decreased TLR4 gene expression in leukemic leukocyte populations},
journal = {Experimental and Molecular Pathology},
year = {2009},
volume = {87},
pages = {117--126},
number = {2},
month = oct,
abstract = {Toll-like receptor 4 (TLR4) is one member of a class of pattern recognition
receptors that play a significant role in the physiologic innate
immune response. As leukemia is a disease state that may be associated
with a compromised immune system, it was hypothesized that depressed
TLR4 function resulting from decreased gene expression might be related
to the development and further sustained presence of a leukemic clone
of cells. This study thus analyzed gene expression of TLR4 in groups
of lymphocytic leukemia cases, myeloid leukemia cases, cases of myeloid
leukemia in remission, and normal controls by real-time quantitative
reverse transcription-PCR (qRT-PCR). It was observed that TLR4 gene
expression was indeed decreased to a statistically significant degree
(P < 0.05) in both the lymphocytic leukemic subset and myeloid leukemic
subset when compared to normal controls. Thus, further study is warranted
into determining whether this decreased TLR4 expression contributes
to the pathogenesis of leukemic clone development through an associated
depressed immune surveillance as well as whether TLR4 agonists might
serve to effectively strengthen the response of the immune system
in battling leukemic burden.},
issn = {0014-4800},
keywords = {TLR4, qRT-PCR, Gene expression, Lymphocytic leukemia, Myeloid leukemia},
url = {http://www.sciencedirect.com/science/article/B6WFB-4WV15T7-2/2/2b655cac4ec30d2fdefd0ff01ef5dd6d}
}
@ARTICLE{Webber2008,
author = {Webber, Andrea L. and Hodor, Paul and Thut, Catherine J. and Vogt,
Thomas F. and Zhang, Theresa and Holder, Daniel J. and Petrukhin,
Konstantin},
title = {Dual role of Nr2e3 in photoreceptor development and maintenance},
journal = {Experimental Eye Research},
year = {2008},
volume = {87},
pages = {35--48},
number = {1},
month = jul,
abstract = {Nr2e3 is a photoreceptor-specific nuclear receptor believed to play
a role in photoreceptor development, differentiation, and survival.
Much research has focused on the interaction of Nr2e3 with other
transcription factors in determining the milieu of target gene expression
in photoreceptors of the neonatal and adult retina. To investigate
the downstream targets of Nr2e3 and thereby shed light on the functional
pathways relevant to photoreceptor development and maintenance, expression
profiling was performed on retinas from two different mouse knockout
lines, one containing a targeted disruption of the Nr2e3 gene (Nr2e3-/-),
the other containing a spontaneous null allele of the Nr2e3 locus
(rd7). Using whole genome microarrays, mRNA expression profiles of
retinas from the two mutant strains were compared to those of wildtype
C57BL/6 mice over a time course that ranged from postnatal day (p)
2 to 6 months of age (p180). Additionally, expression profiling was
performed on retinal explants treated with a putative NR2E3 agonist.
The molecular profiling of Nr2e3-/- and rd7/rd7 retinas identified
281 putative Nr2e3-dependent genes that were differentially expressed
between wildtype and mutant retinas during at least one time point.
Consistent with previous reports that Nr2e3 is necessary for the
repression of cone-specific genes, increased expression of cone-specific
genes was observed in the mutant samples, thereby providing proof-of-concept
for the microarray screen. Further annotation of these data sets
revealed ten predominant functional classes involved in the Nr2e3-mediated
development and/or maintenance of photoreceptors. Interestingly,
differences in the expression of Nr2e3-dependent genes exhibited
two distinct temporal patterns. One group of genes showed a sustained
difference in expression as compared to wildtype over the entire
time course of the study, whereas a second group showed only transient
differences which were largest around p10. Comparison of gene expression
changes in Nr2e3-/- and rd7/rd7 retinas with those uncovered by treating
retinal explants with a putative NR2E3 agonist revealed four genes
that were down-regulated in mutant retinas that lack Nr2e3 function
but were up-regulated in agonist-treated explants. These results
strongly suggest that the four genes may be direct targets of Nr2e3.
Our identification of two sets of Nr2e3-regulated genes provides
further evidence of a dual role for Nr2e3 in specification of photoreceptor
fate during development as well as photoreceptor maintenance in the
adult.},
issn = {0014-4835},
keywords = {Nr2e3, nuclear receptor, rd7, photoreceptor, retinal degeneration,
expression profiling, microarray},
url = {http://www.sciencedirect.com/science/article/B6WFD-4SC78VN-1/2/4e5bdbe882684513f31f6267fb6e55d4}
}
@ARTICLE{Webber2009,
author = {Webber, Mark A. and Bailey, Andrew M. and Blair, Jessica M. A. and
Morgan, Eirwen and Stevens, Mark P. and Hinton, Jay C. D. and Ivens,
Al and Wain, John and Piddock, Laura J. V.},
title = {The Global Consequence of Disruption of the AcrAB-TolC Efflux Pump
in Salmonella enterica Includes Reduced Expression of SPI-1 and Other
Attributes Required To Infect the Host},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {4276--4285},
number = {13},
month = jul,
abstract = {The mechanisms by which RND pumps contribute to pathogenicity are
currently not understood. Using the AcrAB-TolC system as a paradigm
multidrug-resistant efflux pump and Salmonella enterica serovar Typhimurium
as a model pathogen, we have demonstrated that AcrA, AcrB, and TolC
are each required for efficient adhesion to and invasion of epithelial
cells and macrophages by Salmonella in vitro. In addition, AcrB and
TolC are necessary for Salmonella to colonize poultry. Mutants lacking
acrA, acrB, or tolC showed differential expression of major operons
and proteins involved in pathogenesis. These included chemotaxis
and motility genes, including cheWY and flgLMK and 14 Salmonella
pathogenicity island (SPI)-1-encoded type III secretion system genes,
including sopE, and associated effector proteins. Reverse transcription-PCR
confirmed these data for identical mutants in two other S. Typhimurium
backgrounds. Western blotting showed reduced production of SipA,
SipB, and SipC. The absence of AcrB or TolC also caused widespread
repression of chemotaxis and motility genes in these mutants, and
for acrB::aph, this was associated with decreased motility. For mutants
lacking a functional acrA or acrB gene, the nap and nir operons were
repressed, and both mutants grew poorly in anaerobic conditions.
All phenotypes were restored to that of the wild type by trans-complementation
with the wild-type allele of the respective inactivated gene. These
data explain how mutants lacking a component of AcrAB-TolC are attenuated
and that this phenotype is a result of decreased expression of numerous
genes encoding proteins involved in pathogenicity. The link between
antibiotic resistance and pathogenicity establishes the AcrAB-TolC
system as fundamental to the biology of Salmonella.},
url = {http://jb.asm.org/cgi/content/abstract/191/13/4276}
}
@ARTICLE{Weber2007,
author = {Weber, Andreas P.M. and Weber, Katrin L. and Carr, Kevin and Wilkerson,
Curtis and Ohlrogge, John B.},
title = {Sampling the Arabidopsis Transcriptome with Massively Parallel Pyrosequencing},
journal = {Plant Physiology},
year = {2007},
volume = {144},
pages = {32--42},
number = {1},
month = may,
abstract = {Massively parallel sequencing of DNA by pyrosequencing technology
offers much higher throughput and lower cost than conventional Sanger
sequencing. Although extensively used already for sequencing of genomes,
relatively few applications of massively parallel pyrosequencing
to transcriptome analysis have been reported. To test the ability
of this technology to provide unbiased representation of transcripts,
we analyzed mRNA from Arabidopsis (Arabidopsis thaliana) seedlings.
Two sequencing runs yielded 541,852 expressed sequence tags (ESTs)
after quality control. Mapping of the ESTs to the Arabidopsis genome
and to The Arabidopsis Information Resource 7.0 cDNA models indicated:
(1) massively parallel pyrosequencing detected transcription of 17,449
gene loci providing very deep coverage of the transcriptome. Performing
a second sequencing run only increased the number of genes identified
by 10%, but increased the overall sequence coverage by 50%. (2) Mapping
of the ESTs to their predicted full-length transcripts indicated
that all regions of the transcript were well represented regardless
of transcript length or expression level. Furthermore, short, medium,
and long transcripts were equally represented. (3) Over 16,000 of
the ESTs that mapped to the genome were not represented in the existing
dbEST database. In some cases, the ESTs provide the first experimental
evidence for transcripts derived from predicted genes, and, for at
least 60 locations in the genome, pyrosequencing identified likely
protein-coding sequences that are not now annotated as genes. Together,
the results indicate massively parallel pyrosequencing provides novel
information helpful to improve the annotation of the Arabidopsis
genome. Furthermore, the unbiased representation of transcripts will
be particularly useful for gene discovery and gene expression analysis
of nonmodel plants with less complete genomic information.},
url = {http://www.plantphysiol.org/cgi/content/abstract/144/1/32}
}
@ARTICLE{Weber2005,
author = {Weber, Frank and Shen, Lei and Aldred, Micheala A. and Morrison,
Carl D. and Frilling, Andrea and Saji, Motoyasu and Schuppert, Frank
and Broelsch, Christoph E. and Ringel, Matthew D. and Eng, Charis},
title = {Genetic Classification of Benign and Malignant Thyroid Follicular
Neoplasia Based on a Three-Gene Combination},
journal = {J. Clin. Endocrinol. Metab.},
year = {2005},
volume = {90},
pages = {2512--2521},
number = {5},
month = may,
abstract = {Thyroid carcinoma is a common endocrine cancer with a favorable prognosis
if subjected to timely treatment. However, the clinical identification
of follicular thyroid carcinoma (FTC) among patients with benign
thyroid nodules is still a challenge. Preoperative fine needle aspiration-based
cytology cannot always differentiate follicular carcinomas from benign
follicular neoplasias. Because current methods fail to improve preoperative
diagnosis of thyroid nodules, new molecular-based diagnoses should
be explored. We conducted a microarray-based study to reveal the
genetic profiles unique to FTC and follicular adenomas (FAs), to
identify the most parsimonious number of genes that could accurately
differentiate between benign and malignant follicular thyroid neoplasia.
We confirmed our data by quantitative RT-PCR and immunohistochemistry
in two independent validation sets with a total of 114 samples. We
were able to identify three genes, cyclin D2 (CCND2), protein convertase
2 (PCSK2), and prostate differentiation factor (PLAB), that allow
the accurate molecular classification of FTC and FA. Two independent
validation sets revealed that the combination of these three genes
could differentiate FTC from FA with a sensitivity of 100%, specificity
of 94.7%, and accuracy of 96.7%. In addition, our model allowed the
identification of follicular variants of papillary thyroid carcinoma
with an accuracy of 85.7%. Three-gene profiling of thyroid nodules
can accurately predict the diagnosis of FTC and FA with high sensitivity
and specificity, thus identifying promising targets for further investigation
to ultimately improve preoperative diagnosis.},
url = {http://jcem.endojournals.org/cgi/content/abstract/90/5/2512}
}
@ARTICLE{Weber2006,
author = {Weber, Isabella and Assmann, Daniela and Thines, Eckhard and Steinberg,
Gero},
title = {Polar Localizing Class V Myosin Chitin Synthases Are Essential during
Early Plant Infection in the Plant Pathogenic Fungus Ustilago maydis},
journal = {PLANT CELL},
year = {2006},
volume = {18},
pages = {225--242},
number = {1},
month = jan,
abstract = {Fungal chitin synthases (CHSs) form fibers of the cell wall and are
crucial for substrate invasion and pathogenicity. Filamentous fungi
contain up to 10 CHSs, which might reflect redundant functions or
the complex biology of these fungi. Here, we investigate the complete
repertoire of eight CHSs in the dimorphic plant pathogen Ustilago
maydis. We demonstrate that all CHSs are expressed in yeast cells
and hyphae. Green fluorescent protein (GFP) fusions to all CHSs localize
to septa, whereas Chs5-GFP, Chs6-GFP, Chs7-yellow fluorescent protein
(YFP), and Myosin chitin synthase1 (Mcs1)-YFP were found at growth
regions of yeast-like cells and hyphae, indicating that they participate
in tip growth. However, only the class IV CHS genes chs7 and chs5
are crucial for shaping yeast cells and hyphae ex planta. Although
most CHS mutants were attenuated in plant pathogenicity, {Delta}chs6,
{Delta}chs7, and {Delta}mcs1 mutants were drastically reduced in
virulence. {Delta}mcs1 showed no morphological defects in hyphae,
but Mcs1 became essential during invasion of the plant epidermis.
{Delta}mcs1 hyphae entered the plant but immediately lost growth
polarity and formed large aggregates of spherical cells. Our data
show that the polar class IV CHSs are essential for morphogenesis
ex planta, whereas the class V myosin-CHS is essential during plant
infection.},
url = {http://www.plantcell.org/cgi/content/abstract/18/1/225}
}
@ARTICLE{Weber2010,
author = {Weber, Jessica A. and Baxter, David H. and Zhang, Shile and Huang,
David Y. and How Huang, Kuo and Jen Lee, Ming and Galas, David J.
and Wang, Kai},
title = {The MicroRNA Spectrum in 12 Body Fluids},
journal = {Clin. Chem.},
year = {2010},
volume = {56},
pages = {1733--1741},
number = {11},
month = nov,
abstract = {BACKGROUNDMicroRNAs (miRNAs) are small, noncoding RNAs that play an
important role in regulating various biological processes through
their interaction with cellular messenger RNAs. Extracellular miRNAs
in serum, plasma, saliva, and urine have recently been shown to be
associated with various pathological conditions including cancer.
METHODSWith the goal of assessing the distribution of miRNAs and
demonstrating the potential use of miRNAs as biomarkers, we examined
the presence of miRNAs in 12 human body fluids and urine samples
from women in different stages of pregnancy or patients with different
urothelial cancers. Using quantitative PCR, we conducted a global
survey of the miRNA distribution in these fluids. RESULTSmiRNAs were
present in all fluids tested and showed distinct compositions in
different fluid types. Several of the highly abundant miRNAs in these
fluids were common among multiple fluid types, and some of the miRNAs
were enriched in specific fluids. We also observed distinct miRNA
patterns in the urine samples obtained from individuals with different
physiopathological conditions. CONCLUSIONSMicroRNAs are ubiquitous
in all the body fluid types tested. Fluid type-specific miRNAs may
have functional roles associated with the surrounding tissues. In
addition, the changes in miRNA spectra observed in the urine samples
from patients with different urothelial conditions demonstrates the
potential for using concentrations of specific miRNAs in body fluids
as biomarkers for detecting and monitoring various physiopathological
conditions.},
url = {http://www.clinchem.org/cgi/content/abstract/56/11/1733}
}
@ARTICLE{Weber2006a,
author = {Weber, P. S. D. and Madsen-Bouterse, S. A. and Rosa, G. J. M. and
Sipkovsky, S. and Ren, X. and Almeida, P. E. and Kruska, R. and Halgren,
R. G. and Barrick, J. L. and Burton, J. L.},
title = {Analysis of the bovine neutrophil transcriptome during glucocorticoid
treatment},
journal = {Physiol Genomics},
year = {2006},
volume = {28},
pages = {97--112},
number = {1},
month = dec,
abstract = {The objective of this study was to characterize a large portion of
the bovine neutrophil transcriptome following treatment with the
anti-inflammatory glucocorticoid dexamethasone (Dex). Total RNA was
isolated from blood neutrophils of healthy cattle (5 castrated male
Holsteins) immediately following cell purification (0 h) or after
ex vivo aging for 4 h with or without added Dex. Additional neutrophils
were cotreated with a glucocorticoid receptor (GR) antagonist (RU486)
and Dex for 4 h. RNA was amplified, dye labeled (Cy3 or Cy5), and
hybridized to a series of National Bovine Functional Genomics Consortium
(NBFGC) microarrays. LOWESS data normalization followed by mixture
model analyses showed that 11.15% of the spotted NBFGC cDNAs (2,036/18,263)
were expressed in 4-h (untreated) neutrophils. Subsequent two-step
mixed-model analysis detected (P [≤] 0.05) 1,109 differentially
expressed genes, of which contrast analysis indicated those that
were independently responsive to aging (1,064), Dex (502), RU486
+ Dex (141), or RU486 (357). In silico analysis revealed that 416
of the differentially expressed genes are unknown, 59 did not cluster
well based on known function, and 634 clustered into 20 ontological
categories. Independent validation of differential expression was
done for 14 of the putatively Dex-responsive genes across these categories.
Results showed that Dex induced rapid translocation of GR into the
neutrophil nucleus and signaled dramatic alterations in expression
of genes that delay apoptosis, enhance bactericidal activity, and
promote tissue remodeling without inflammation or fibrosis. Thus
these findings revealed hitherto unappreciated plasticity of blood
neutrophils and potentially novel anti-inflammatory/wound-healing
actions of glucocorticoids.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/28/1/97}
}
@ARTICLE{Webster2009,
author = {Webster, Kylie E. and Walters, Stacey and Kohler, Rachel E. and Mrkvan,
Tomas and Boyman, Onur and Surh, Charles D. and Grey, Shane T. and
Sprent, Jonathan},
title = {In vivo expansion of T reg cells with IL-2-mAb complexes: induction
of resistance to EAE and long-term acceptance of islet allografts
without immunosuppression},
journal = {J. Exp. Med.},
year = {2009},
volume = {206},
pages = {751--760},
number = {4},
month = apr,
abstract = {Via a transcription factor, Foxp3, immunoregulatory CD4+CD25+ T cells
(T reg cells) play an important role in suppressing the function
of other T cells. Adoptively transferring high numbers of T reg cells
can reduce the intensity of the immune response, thereby providing
an attractive prospect for inducing tolerance. Extending our previous
findings, we describe an in vivo approach for inducing rapid expansion
of T reg cells by injecting mice with interleukin (IL)-2 mixed with
a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2-IL-2
mAb complexes for a short period of 3 d induces a marked (>10-fold)
increase in T reg cell numbers in many organs, including the liver
and gut as well as the spleen and lymph nodes, and a modest increase
in the thymus. The expanded T reg cells survive for 1-2 wk and are
highly activated and display superior suppressive function. Pretreating
with the IL-2-IL-2 mAb complexes renders the mice resistant to induction
of experimental autoimmune encephalomyelitis; combined with rapamycin,
the complexes can also be used to treat ongoing disease. In addition,
pretreating mice with the complexes induces tolerance to fully major
histocompatibility complex-incompatible pancreatic islets in the
absence of immunosuppression. Tolerance is robust and the majority
of grafts are accepted indefinitely. The approach described for T
reg cell expansion has clinical potential for treating autoimmune
disease and promoting organ transplantation.},
url = {http://jem.rupress.org/cgi/content/abstract/206/4/751}
}
@ARTICLE{Webster2011b,
author = {Webster, L. M. I. And Mello, L. V. And Mougeot, F. And Martinez-padilla,
J. And Paterson, S. And Piertney, S. B.},
title = {Identification of genes responding to nematode infection in red grouse},
journal = {Molecular Ecology Resources},
year = {2011},
volume = {11},
pages = {305--313},
number = {2},
abstract = {Abstract The identification of genes involved in a host’s response
to parasite infection provides both a means for understanding the
pathways involved in immune defence and a target for examining host–parasite
co-evolution. Most studies rely on a candidate gene approach derived
from model systems to identify gene targets of interest, and there
have been a dearth of studies geared towards providing a holistic
overview of immune response from natural populations. We carried
out an experiment in a natural population of red grouse (Lagopus
lagopus scoticus) to manipulate levels of Trichostrongylus tenuis
parasite infection. The transcriptomic response of individuals was
examined from standard cDNA and suppressive subtractive hybridization
(SSH) libraries produced from gut, liver and spleen, enriching for
genes expressed in response to T. tenuis infection. A total of 2209
and 3716 unique transcript sequences were identified from the cDNA
and SSH libraries, respectively. Forty-five of these had Gene Ontology
annotation associated with immune response. Some of these genes have
previously been reported from laboratory-based studies of model species
as important in immune response to gastrointestinal parasite infection;
however, multiple novel genes were also identified. These may reveal
novel pathways involved in the host response of grouse to T. tenuis
and provide a resource that can be utilized as candidate genes in
other species.},
doi = {10.1111/j.1755-0998.2010.02912.x},
issn = {1755-0998},
keywords = {candidate genes, immune response, Lagopus lagopus scoticus, suppressive
subtractive hybridization, Trichostrongylus tenuis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-0998.2010.02912.x}
}
@ARTICLE{Webster2010,
author = {Webster, L. M. I. And Mello, L. V. And Mougeot, F. And Martinez-padilla,
J. And Paterson, S. And Piertney, S. B.},
title = {Permanent genetic resources article: identification of genes responding
to nematode infection in red grouse},
journal = {Molecular Ecology Resources},
year = {2010},
pages = {no--no},
abstract = {Abstract The identification of genes involved in a host’s response
to parasite infection provides both a means for understanding the
pathways involved in immune defence and a target for examining host–parasite
co-evolution. Most studies rely on a candidate gene approach derived
from model systems to identify gene targets of interest, and there
have been a dearth of studies geared towards providing a holistic
overview of immune response from natural populations. We carried
out an experiment in a natural population of red grouse (Lagopus
lagopus scoticus) to manipulate levels of Trichostrongylus tenuis
parasite infection. The transcriptomic response of individuals was
examined from standard cDNA and suppressive subtractive hybridization
(SSH) libraries produced from gut, liver and spleen, enriching for
genes expressed in response to T. tenuis infection. A total of 2209
and 3716 unique transcript sequences were identified from the cDNA
and SSH libraries, respectively. Forty-five of these had Gene Ontology
annotation associated with immune response. Some of these genes have
previously been reported from laboratory-based studies of model species
as important in immune response to gastrointestinal parasite infection;
however, multiple novel genes were also identified. These may reveal
novel pathways involved in the host response of grouse to T. tenuis
and provide a resource that can be utilized as candidate genes in
other species.},
issn = {1755-0998},
keywords = {candidate genes, immune response, Lagopus lagopus scoticus, suppressive
subtractive hybridization, Trichostrongylus tenuis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1755-0998.2010.02912.x}
}
@ARTICLE{Webster2011,
author = {Webster, L. M. I. And Paterson, S. And Mougeot, F. And Martinez-padilla,
J. And Piertney, S. B.},
title = {Transcriptomic response of red grouse to gastro-intestinal nematode
parasites and testosterone: implications for population dynamics},
journal = {Molecular Ecology},
year = {2011},
volume = {20},
pages = {920--931},
number = {5},
abstract = {Abstract A central issue in ecology is in understanding the relative
influences of intrinsic and extrinsic effects on population regulation.
Previous studies on the cyclic population dynamics of red grouse
(Lagopus lagopus scoticus) have emphasized the destabilizing effects
of either nematode parasites or territorial behaviour and aggression.
The potential interacting effects of these processes, mediated through
density-dependent, environmentally induced alterations of host immunocompetence
influencing susceptibility to parasites have not been considered.
Male red grouse at high density are more aggressive, associated with
increased testosterone, which potentially could lead to reduced immunocompetence
at a stage when parasites are most prevalent. This could depress
individual condition, breeding performance and survival and thus
drive or contribute to overall reductions in population size. Here,
we characterize the transcriptomic response of grouse to nematode
parasite infection and investigate how this is subsequently affected
by testosterone, using a microarray approach contrasting red grouse
with high and low parasite load at both high and low testosterone
titre. A suite of 52 transcripts showed a significant level of up-regulation
to either chronic parasite load or experimental parasite infection.
Of these, 51 (98%) showed a reduced level of expression under conditions
of high parasite load and high testosterone. The genes up-regulated
by parasites and then down-regulated at high testosterone titre were
not necessarily associated with immune response, as might be intuitively
expected. The results are discussed in relation to the fitness and
condition of individual red grouse and factors influencing the regulation
of abundance in natural populations.},
doi = {10.1111/j.1365-294X.2010.04906.x},
issn = {1365-294X},
keywords = {Host–parasite interactions, Lagopus lagopus scoticus, transcriptomics,
Trichostrongylus tenuis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2010.04906.x}
}
@ARTICLE{Webster2006,
author = {Webster, Maree J.},
title = {Tissue preparation and banking},
journal = {Prog Brain Res},
year = {2006},
volume = {Volume 158},
pages = {3--14},
abstract = {With the increasing application of genomic and proteomic technologies
to the research of neurological and psychiatric disorders it has
become imperative that the postmortem tissue utilized be of the highest
quality possible. Every step of the research design, from identifying
donors, acquiring sufficient information for accurate diagnosis,
to assessing tissue quality has to be carefully considered. In order
to obtain high-quality RNA and protein from the postmortem brain
tissue a standardized system of brain collection, dissection, and
storage must be employed and key ante- and postmortem factors must
be considered. Reliable RNA expression and protein data can be obtained
from postmortem brains with relatively long postmortem intervals
(PMIs) if the agonal factors and acidosis are not severe. While pH
values are correlated with RNA integrity number (RIN), a higher pH
does not guarantee intact RNA. Consequently RNA integrity must be
assessed for every case before it is included in a study. An analysis
of anti- and postmortem factors in a large brain collection has revealed
that several diagnostic groups have significantly lower pH values
than other groups, however, they do not have significantly lower
RIN values. Moreover, the lower pH of these groups is not entirely
due to agonal factors and/or smoking, indicating that these subjects
may have additional metabolic abnormalities that contribute to the
lower pH values.},
booktitle = {Functional Genomics and Proteomics in the Clinical Neurosciences},
editor = {Hemby, S.E. and Bahn, S.},
issn = {0079-6123},
publisher = {Elsevier},
url = {http://www.sciencedirect.com/science/article/B7CV6-4M28MCT-3/2/d4bf06efb2f17732a5893810a363a529}
}
@ARTICLE{Webster2011a,
author = {Webster, Maree J. and Elashoff, Michael and Weickert, Cynthia Shannon},
title = {Molecular evidence that cortical synaptic growth predominates during
the first decade of life in humans},
journal = {International Journal of Developmental Neuroscience},
year = {2011},
volume = {29},
pages = {225--236},
number = {3},
month = may,
abstract = {Theories concerning the pathology of human neurodevelopmental disorders
that emerge in adolescence, such as schizophrenia, often hypothesize
that there may be a failure of normal cortical synaptic loss or pruning.
However, direct evidence that synaptic regression is a major developmental
event in the adolescent human cortex is limited. Furthermore, developmental
work in rodents suggested that synaptic regression in adolescence
is not a major feature of cortical development. Thus, we set out
to determine when and to what extent molecular markers of synaptic
terminals [synaptophysin (SYP), SNAP-25, syntaxin1A (STX1A), and
vesicle-associated membrane protein 1 (VAMP1)] are reduced during
postnatal human life spanning from 1 month to 45 years (n = 69) using
several different quantitative methods, microarray, qPCR and immunoblotting.
We found little evidence for a consistent decrease in synaptic-related
molecular markers at any time point, but instead found clear patterns
of gradual increases in expression of some presynaptic markers with
postnatal age (including SNAP-25, VAMP1 and complexin 1 (CPLX1) mRNAs
and 6/6 presynaptic proteins evaluated). A measure of synaptic plasticity
[growth-associated protein of 43 kDa (GAP-43)] was elevated in neonates,
and continued robust expression throughout life. Since CPLX1 protein
is enriched in inhibitory terminals we also tested if the protein
product of complexin 2 (CPLX2), which is enriched in excitatory neurons,
is more specifically reduced in development. In contrast to CPLX1,
which showed a steady increase in both mRNA and protein levels during
postnatal development (both r > 0.58, p < 0.001), CPLX2 mRNA decreased
from infants to toddlers (r = -0.56, p < 0.001), while CPLX2 protein
showed a steady increase until young adulthood (r = 0.55, p < 0.001).
Furthermore, we found that indices of the dendrites [microtubule
associated protein 2 (MAP2)] and spines (spinophilin and postsynaptic
density protein of 95 kDa (PSD95)] showed some evidence of reduction
over time at the mRNA level but the opposite pattern, of a developmental
increase, was found for PSD95 and spinophilin protein levels. Taken
together, the postnatal changes in molecular components of synapses
supports the notion that growth and strengthening of synaptic elements
is a major developmental event occurring in the frontal cortex throughout
childhood and that maintenance of steady state levels of synapse-associated
molecules may predominate during human adolescence.},
booktitle = {Schizophrenia},
issn = {0736-5748},
keywords = {mRNA, Gene expression, Postmortem, Gene, Ontogeny, Microarray},
url = {http://www.sciencedirect.com/science/article/pii/S0736574810003886}
}
@ARTICLE{Webster2009a,
author = {Webster, Rebecca J. and Giles, Keith M. and Price, Karina J. and
Zhang, Priscilla M. and Mattick, John S. and Leedman, Peter J.},
title = {Regulation of Epidermal Growth Factor Receptor Signaling in Human
Cancer Cells by MicroRNA-7},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {5731--5741},
number = {9},
month = feb,
abstract = {The epidermal growth factor receptor (EGFR) is frequently overexpressed
in cancer and is an important therapeutic target. Aberrant expression
and function of microRNAs have been associated with tumorigenesis.
Bioinformatic predictions suggest that the human EGFR mRNA 3'-untranslated
region contains three microRNA-7 (miR-7) target sites, which are
not conserved across mammals. We found that miR-7 down-regulates
EGFR mRNA and protein expression in cancer cell lines (lung, breast,
and glioblastoma) via two of the three sites, inducing cell cycle
arrest and cell death. Because miR-7 was shown to decrease EGFR mRNA
expression, we used microarray analysis to identify additional mRNA
targets of miR-7. These included Raf1 and multiple other genes involved
in EGFR signaling and tumorigenesis. Furthermore, miR-7 attenuated
activation of protein kinase B (Akt) and extracellular signal-regulated
kinase 1/2, two critical effectors of EGFR signaling, in different
cancer cell lines. These data establish an important role for miR-7
in controlling mRNA expression and indicate that miR-7 has the ability
to coordinately regulate EGFR signaling in multiple human cancer
cell types.},
url = {http://www.jbc.org/cgi/content/abstract/284/9/5731}
}
@ARTICLE{Wechter2008,
author = {Wechter, W Patrick and Levi, Amnon and Harris, Karen and Davis, Angela
and Fei, Zhangjun and Katzir, Nurit and Giovannoni, James and Salman-Minkov,
Ayelet and Hernandez, Alvaro and Thimmapuram, Jyothi and Tadmor,
Yaakov and Portnoy, Vitaly and Trebitsh, Tova},
title = {Gene expression in developing watermelon fruit},
journal = {BMC Genomics},
year = {2008},
volume = {9},
pages = {275},
number = {1},
abstract = {BACKGROUND:Cultivated watermelon form large fruits that are highly
variable in size, shape, color, and content, yet have extremely narrow
genetic diversity. Whereas a plethora of genes involved in cell wall
metabolism, ethylene biosynthesis, fruit softening, and secondary
metabolism during fruit development and ripening have been identified
in other plant species, little is known of the genes involved in
these processes in watermelon. A microarray and quantitative Real-Time
PCR-based study was conducted in watermelon [Citrullus lanatus (Thunb.)
Matsum. & Nakai var. lanatus] in order to elucidate the flow of events
associated with fruit development and ripening in this species. RNA
from three different maturation stages of watermelon fruits, as well
as leaf, were collected from field grown plants during three consecutive
years, and analyzed for gene expression using high-density photolithography
microarrays and quantitative PCR.RESULTS:High-density photolithography
arrays, composed of probes of 832 EST-unigenes from a subtracted,
fruit development, cDNA library of watermelon were utilized to examine
gene expression at three distinct time-points in watermelon fruit
development. Analysis was performed with field-grown fruits over
three consecutive growing seasons. Microarray analysis identified
three hundred and thirty-five unique ESTs that are differentially
regulated by at least two-fold in watermelon fruits during the early,
ripening, or mature stage when compared to leaf. Of the 335 ESTs
identified, 211 share significant homology with known gene products
and 96 had no significant matches with any database accession. Of
the modulated watermelon ESTs related to annotated genes, a significant
number were found to be associated with or involved in the vascular
system, carotenoid biosynthesis, transcriptional regulation, pathogen
and stress response, and ethylene biosynthesis. Ethylene bioassays,
performed with a closely related watermelon genotype with a similar
phenotype, i.e. seeded, bright red flesh, dark green rind, etc.,
determined that ethylene levels were highest during the green fruit
stage followed by a decrease during the white and pink fruit stages.
Additionally, quantitative Real-Time PCR was used to validate modulation
of 127 ESTs that were differentially expressed in developing and
ripening fruits based on array analysis.CONCLUSION:This study identified
numerous ESTs with putative involvement in the watermelon fruit developmental
and ripening process, in particular the involvement of the vascular
system and ethylene. The production of ethylene during fruit development
in watermelon gives further support to the role of ethylene in fruit
development in non-climacteric fruits.},
doi = {10.1186/1471-2164-9-275},
issn = {1471-2164},
pubmedid = {18534026},
url = {http://www.biomedcentral.com/1471-2164/9/275}
}
@ARTICLE{Wecker2009,
author = {Wecker, Patricia and Klockow, Christine and Ellrott, Andreas and
Quast, Christian and Langhammer, Philipp and Harder, Jens and Glöckner,
Frank},
title = {Transcriptional response of the model planctomycete Rhodopirellula
baltica SH1T to changing environmental conditions},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {410},
number = {1},
abstract = {BACKGROUND:The marine model organism Rhodopirellula baltica SH1T was
the first Planctomycete to have its genome completely sequenced.
The genome analysis predicted a complex lifestyle and a variety of
genetic opportunities to adapt to the marine environment. Its adaptation
to environmental stressors was studied by transcriptional profiling
using a whole genome microarray.RESULTS:Stress responses to salinity
and temperature shifts were monitored in time series experiments.
Chemostat cultures grown in mineral medium at 28°C were compared
to cultures that were shifted to either elevated (37°C) or reduced
(6°C) temperatures as well as high salinity (59.5‰) and observed
over 300 min. Heat shock showed the induction of several known chaperone
genes. Cold shock altered the expression of genes in lipid metabolism
and stress proteins. High salinity resulted in the modulation of
genes coding for compatible solutes, ion transporters and morphology.
In summary, over 3000 of the 7325 genes were affected by temperature
and/or salinity changes.CONCLUSION:Transcriptional profiling confirmed
that R. baltica is highly responsive to its environment. The distinct
responses identified here have provided new insights into the complex
adaptation machinery of this environmentally relevant marine bacterium.
Our transcriptome study and previous proteome data suggest a set
of genes of unknown functions that are most probably involved in
the global stress response. This work lays the foundation for further
bioinformatic and genetic studies which will lead to a comprehensive
understanding of the biology of a marine Planctomycete.},
doi = {10.1186/1471-2164-10-410},
issn = {1471-2164},
pubmedid = {19725962},
url = {http://www.biomedcentral.com/1471-2164/10/410}
}
@ARTICLE{Weckx2009,
author = {Weckx, Stefan and Allemeersch, Joke and Van der Meulen, Roel and
Vrancken, Gino and Huys, Geert and Vandamme, Peter and Van Hummelen,
Paul and De Vuyst, Luc},
title = {Development and Validation of a Species-Independent Functional Gene
Microarray That Targets Lactic Acid Bacteria},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {6488--6495},
number = {20},
month = oct,
abstract = {During the last few years, genome-related information has become available
for many microorganisms, including important food-related bacteria.
Lactic acid bacteria (LAB) are important industrially in the production
of fermented foods such as dairy products, sausages, sourdoughs,
and vegetables. Despite their limited metabolic capacity, LAB contribute
considerably to important characteristics of fermented foods, such
as flavor and texture. In the present study, a species-independent
functional gene microarray was developed that targets 406 genes that
play key roles in the production of sugar catabolites, bacteriocins,
exopolysaccharides, and aromas, in probiotic and biosafety characteristics,
and in the stress response. Also, genes linked to negative traits,
such as antibiotic resistance and virulence, are represented. As
LAB ecosystems contain a variety of species, there was a more global
focus on these specific functional properties. Thus, an algorithm
was used to design gene-specific oligonucleotides that preferably
hybridize with multiple LAB species, thereby allowing controlled
cross-hybridization. For proof of concept, the microarray composed
of 2,269 30-mer oligonucleotides focused on LAB species that are
prevalent in sourdough ecosystems. Validation hybridizations using
DNA and RNA from 18 LAB strains, covering 86% of all the oligonucleotides,
showed that there were wide ranges in intensity and high reproducibility
between microarrays.},
url = {http://aem.asm.org/cgi/content/abstract/75/20/6488}
}
@ARTICLE{Wedhas2005,
author = {Wedhas, Nia and Klamut, Henry J. and Dogra, Charu and Srivastava,
Apurva K. and Mohan, Subburaman and Kumar, Ashok},
title = {Inhibition of mechanosensitive cation channels inhibits myogenic
differentiation by suppressing the expression of myogenic regulatory
factors and caspase-3 activity},
journal = {FASEB J},
year = {2005},
volume = {19},
pages = {1986--1997},
number = {14},
month = dec,
abstract = {Mechanosensitive cation channels (MSC) are ubiquitous in eukaryotic
cell types. However, the physiological functions of MSC in several
tissues remain in question. In this study we have investigated the
role of MSC in skeletal myogenesis. Treatment of C2C12 myoblasts
with gadolinium ions (MSC blocker) inhibited myotube formation and
the myogenic index in differentiation medium (DM). The enzymatic
activity of creatine kinase (CK) and the expression of myosin heavy
chain-fast twitch (MyHCf) in C2C12 cultures were also blocked in
response to gadolinium. Treatment of C2C12 myoblasts with gadolinium
ions did not affect the expression of either cyclin A or cyclin D1
in DM. Other inhibitors of MSC such as streptomycin and GsTMx-4 also
suppressed the expression of CK and MyHCf in C2C12 cultures. The
inhibitory effect of gadolinium ions on myogenic differentiation
was reversible and independent of myogenic cell type. Real-time-polymerase
chain reaction analysis revealed that inhibition of MSC decreases
the expression of myogenic transcription factors MyoD, myogenin,
and Myf-5. Furthermore, the activity of skeletal {alpha}-actin promoter
was suppressed on MSC blockade. Treatment of C2C12 myoblasts with
gadolinium ions prevented differentiation-associated cell death and
inhibited the cleavage of poly (ADP-ribose) polymerase and activation
of caspase-3. On the other hand, delivery of active caspase-3 protein
to C2C12 myoblasts reversed the inhibitory effect of gadolinium ions
on myogenesis. Our data suggest that inhibition of MSC suppresses
myogenic differentiation by inhibiting the caspase-3 activity and
the expression of myogenic regulatory factors.--Wedhas, N., Klamut,
H. J., Dogra, C., Srivastava, A. K., Mohan, S., Kumar, A. Inhibition
of mechanosensitive cation channels inhibits myogenic differentiation
by suppressing the expression of myogenic regulatory factors and
caspase-3 activity.},
url = {http://www.fasebj.org/cgi/content/abstract/19/14/1986}
}
@ARTICLE{Weedon-FekjA¦r2010,
author = {Weedon-Fekjær, M.S. and Johnsen, G.M. and Anthonisen, E.H. and Sugulle,
M. and Nebb, H.I. and Duttaroy, A.K. and Staff, A.C.},
title = {Expression of Liver X Receptors in Pregnancies Complicated by Preeclampsia},
journal = {Placenta},
year = {2010},
volume = {31},
pages = {818--824},
number = {9},
month = sep,
abstract = {Preeclampsia is a pregnancy-specific disorder associated with hyperlipidemia.
Liver X receptor (LXR) α and LXRβ are key regulators of lipid homeostasis.
In the current study, we investigated expression of LXRα, LXRβ
and their target genes in human term placenta, decidua and subcutaneous
adipose tissue from pregnancies complicated by preeclampsia. Furthermore,
we analyzed the protein levels of LXRα and LXRβ in placenta. We
also analyzed lipid concentrations in term placental tissue. Gene
expression of LXRα, LXRβ and fatty acid transporter CD36 was significantly
decreased in placental tissues, while increased expression was observed
for LXRα in adipose tissue, from pregnancies complicated by preeclampsia.
The placental protein level of LXRβ was reduced, and there was a
positive correlation between placental LXRβ mRNA expression and
placental free fatty acids in preeclampsia. Our results suggest a
possible role for LXRβ as a transcriptional regulator in preeclampsia.},
issn = {0143-4004},
keywords = {Liver X Receptor, Preeclampsia, CD36, Lipids, Decidua, Adipose tissue,
Polyunsaturated fatty acid},
publisher = {W.B. Saunders},
refid = {S0143-4004(10)00245-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0143400410002456?showall=true}
}
@ARTICLE{Weeks2010,
author = {Weeks, Jenni and Galindo, Cristi and Drake, Kenneth and Adams, Garry
and Garner, Harold and Ficht, Thomas},
title = {Brucella melitensis VjbR and C12-HSL regulons: contributions of the
N-dodecanoyl homoserine lactone signaling molecule and LuxR homologue
VjbR to gene expression},
journal = {BMC Microbiology},
year = {2010},
volume = {10},
pages = {167},
number = {1},
abstract = {BACKGROUND:Quorum sensing is a communication system that regulates
gene expression in response to population density and often regulates
virulence determinants. Deletion of the luxR homologue vjbR highly
attenuates intracellular survival of Brucella melitensis and has
been interpreted to be an indication of a role for QS in Brucella
infection. Confirmation for such a role was suggested, but not confirmed,
by the demonstrated in vitro synthesis of an auto-inducer (AI) by
Brucella cultures. In an effort to further delineate the role of
VjbR to virulence and survival, gene expression under the control
of VjbR and AI was characterized using microarray analysis.RESULTS:Analyses
of wildtype B. melitensis and isogenic ?vjbR transciptomes, grown
in the presence and absence of exogenous N-dodecanoyl homoserine
lactone (C12-HSL), revealed a temporal pattern of gene regulation
with variances detected at exponential and stationary growth phases.
Comparison of VjbR and C12-HSL transcriptomes indicated the shared
regulation of 127 genes with all but 3 genes inversely regulated,
suggesting that C12-HSL functions via VjbR in this case to reverse
gene expression at these loci. Additional analysis using a ?vjbR
mutant revealed that AHL also altered gene expression in the absence
of VjbR, up-regulating expression of 48 genes and a luxR homologue
blxR 93-fold at stationary growth phase. Gene expression alterations
include previously un-described adhesins, proteases, antibiotic and
toxin resistance genes, stress survival aids, transporters, membrane
biogenesis genes, amino acid metabolism and transport, transcriptional
regulators, energy production genes, and the previously reported
fliF and virB operons.CONCLUSIONS:VjbR and C12-HSL regulate expression
of a large and diverse number of genes. Many genes identified as
virulence factors in other bacterial pathogens were found to be differently
expressed, suggesting an important contribution to intracellular
survival of Brucella. From these data, we conclude that VjbR and
C12-HSL contribute to virulence and survival by regulating expression
of virulence mechanisms and thus controlling the ability of the bacteria
to survive within the host cell. A likely scenario occurs via QS,
however, operation of such a mechanism remains to be demonstrated.},
doi = {10.1186/1471-2180-10-167},
issn = {1471-2180},
pubmedid = {20529360},
url = {http://www.biomedcentral.com/1471-2180/10/167}
}
@ARTICLE{Weeraratna2007,
author = {Weeraratna, Ashani T. and Kalehua, Audrey and DeLeon, Isoke and Bertak,
Dorothy and Maher, Gregory and Wade, Michael S. and Lustig, Ana and
Becker, Kevin G. and Wood III, William and Walker, Douglas G. and
Beach, Thomas G. and Taub, Dennis D.},
title = {Alterations in immunological and neurological gene expression patterns
in Alzheimer's disease tissues},
journal = {Experimental Cell Research},
year = {2007},
volume = {313},
pages = {450--461},
number = {3},
month = feb,
abstract = {Microarray technology was utilized to isolate disease-specific changes
in gene expression by sampling across inferior parietal lobes of
patients suffering from late onset AD or non-AD-associated dementia
and non-demented controls. Primary focus was placed on understanding
how inflammation plays a role in AD pathogenesis. Gene ontology analysis
revealed that the most differentially expressed genes related to
nervous system development and function and neurological disease
followed by genes involved in inflammation and immunological signaling.
Pathway analysis also implicated a role for chemokines and their
receptors, specifically CXCR4 and CCR3, in AD. Immunohistological
analysis revealed that these chemokine receptors are upregulated
in AD patients. Western analysis demonstrated an increased activation
of PKC, a downstream mediator of chemokine receptor signaling, in
the majority of AD patients. A very specific cohort of genes related
to amyloid beta accumulation and clearance were found to be significantly
altered in AD. The most significantly downregulated gene in this
data set was the endothelin converting enzyme 2 (ECE2), implicated
in amyloid beta clearance. These data were subsequently confirmed
by real-time PCR and Western blot analysis. Together, these findings
open up new avenues of investigation and possible therapeutic strategies
targeting inflammation and amyloid clearance in AD patients.},
issn = {0014-4827},
keywords = {Alzheimer's disease, Endothelin converting enzyme, Inflammation, Aging,
Chemokine},
url = {http://www.sciencedirect.com/science/article/B6WFC-4M7YK1M-1/2/4768d639e967461b10245e39a523f10a}
}
@ARTICLE{Wehbe2006,
author = {Wehbe, Hania and Henson, Roger and Lang, Molly and Meng, Fanyin and
Patel, Tushar},
title = {Pifithrin-{alpha} Enhances Chemosensitivity by a p38 Mitogen-Activated
Protein Kinase-Dependent Modulation of the Eukaryotic Initiation
Factor 4E in Malignant Cholangiocytes},
journal = {J. Pharmacol. Exp. Ther.},
year = {2006},
volume = {319},
pages = {1153--1161},
number = {3},
month = dec,
abstract = {Pifithrin-{alpha} is the lead compound for a novel group of small
molecules that are being developed for use as anticancer agents.
The eukaryotic initiation factor 4E (eIF-4E) is overexpressed in
many cancers, it can mediate sensitivity to therapy, and it may be
regulated by p53. We examined the utility of pifithrin-{alpha} as
an adjunct to therapy for the treatment of human cholangiocarcinoma,
a tumor that is highly refractory to therapy, and we assessed the
involvement of p53-dependent eIF-4E regulation in cellular responses
to pifithrin-{alpha}. The expression of eIF-4E was increased in human
cholangiocarcinomas compared with normal liver. Modulation of eIF-4E
expression by RNA interference enhanced the efficacy of gemcitabine
in KMCH cholangiocarcinoma cells. Preincubation of KMCH cells with
pifithrin-{alpha} enhanced gemcitabine-induced cytotoxicity in an
eIF-4E-dependent manner. Furthermore, pifithrin-{alpha} increased
eIF-4E phosphorylation at serine 209 via activation of p38 mitogen-activated
protein kinase (MAPK). Pifithrin-{alpha} was shown to activate aryl
hydrocarbon receptor (AhR) signaling and p38 MAPK activation. Sequencing
analysis indicated the presence of a functionally inactivating p53
mutation in KMCH cells, and small interfering RNA to p53 did not
modulate chemosensitization by pifithrin-{alpha}. Pifithrin-{alpha}
enhanced chemosensitivity by a mechanism independent of p53 and involving
AhR and p38 MAPK deregulation of eIF-4E phosphorylation. Thus, pifithrin-{alpha}
may prove useful for enhancing chemosensitivity in tumors with mutated
p53. Moreover, modulation of eIF-4E is an attractive therapeutic
target for intervention in cancer treatment.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/319/3/1153}
}
@ARTICLE{Wehbe2006a,
author = {Wehbe, Hania and Henson, Roger and Meng, Fanyin and Mize-Berge, Janna
and Patel, Tushar},
title = {Interleukin-6 Contributes to Growth in Cholangiocarcinoma Cells by
Aberrant Promoter Methylation and Gene Expression},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {10517--10524},
number = {21},
month = nov,
abstract = {The association between chronic inflammation and the development and
progression of malignancy is exemplified in the biliary tract where
persistent inflammation strongly predisposes to cholangiocarcinoma.
The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth
in cholangiocarcinoma by altered gene expression via autocrine mechanisms.
IL-6 can regulate the activity of DNA methyltransferases, and moreover,
aberrant DNA methylation can contribute to carcinogenesis. We therefore
investigated the effect of chronic exposure to IL-6 on methylation-dependent
gene expression and transformed cell growth in human cholangiocarcinoma.
The relationship between autocrine IL-6 pathways, DNA methylation,
and transformed cell growth was assessed using malignant cholangiocytes
stably transfected to overexpress IL-6. Treatment with the DNA methylation
inhibitor 5-aza-2'-deoxycytidine decreased cell proliferation, growth
in soft agar, and methylcytosine content of malignant cholangiocytes.
However, this effect was not observed in IL-6-overexpressing cells.
IL-6 overexpression resulted in the altered expression and promoter
methylation of several genes, including the epidermal growth factor
receptor (EGFR). EGFR promoter methylation was decreased and gene
and protein expression was increased by IL-6. Thus, epigenetic regulation
of gene expression by IL-6 can contribute to tumor progression by
altering promoter methylation and gene expression of growth-regulatory
pathways, such as those involving EGFR. Moreover, enhanced IL-6 expression
may decrease the sensitivity of tumor cells to therapeutic treatments
using methylation inhibitors. These observations have important implications
for cancer treatment and provide a mechanism by which persistent
cytokine stimulation can promote tumor growth. (Cancer Res 2006;
66(21): 10517-24)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/21/10517}
}
@ARTICLE{Wehrhan2011,
author = {Wehrhan, F and Hyckel, P and Amann, K and Ries, J and Stockmann,
P and Schlegel, KA and Neukam, FW and Nkenke, E},
title = {Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of
bone turnover-related cell signalling after bisphosphonate treatment},
journal = {Oral Diseases},
year = {2011},
volume = {17},
pages = {433--442},
number = {4},
abstract = {Oral Diseases (2011) 17, 433–442Objectives:  Bone-destructive
disease treatments include bisphosphonates and antibodies against
receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis
of the jaw (ONJ) is a side-effect. Aetiopathology models failed to
explain their restriction to the jaw. The osteoproliferative transcription
factor Msx-1 is expressed constitutively only in mature jaw bone.
Msx-1 expression might be impaired in bisphosphonate-related ONJ.
This study compared the expression of Msx-1, Bone Morphogenetic Protein
(BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone.Material
and methods:  An automated immunohistochemistry-based alkaline
phosphatase-anti-alkaline phosphatase method was used on ONJ-affected
and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling
index, Bonferroni adjustment). Real-time RT-PCR was performed to
quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels.Results: 
Labelling indices were significantly lower for Msx-1 (PÂ <Â 0.03)
and RANKL (PÂ <Â 0.003) and significantly higher (PÂ <Â 0.02) for
BMP-2 in ONJ compared with healthy bone. Expression was sevenfold
lower (PÂ <Â 0.03) for Msx-1, 22-fold lower (PÂ <Â 0.001) for RANKL
and eightfold higher (P < 0.02) for BMP-2 in ONJ bone.Conclusions: 
Msx-1, RANKL suppression and BMP-2 induction were consistent with
the bisphosphonate-associated osteopetrosis and impaired bone remodelling
in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible
explanation of the exclusivity of ONJ in jaw bone. Functional analyses
of Msx-1- RANKL interaction during bone remodelling should be performed
in the future.},
doi = {10.1111/j.1601-0825.2010.01778.x},
issn = {1601-0825},
keywords = {ONJ, Msx-1, aminobisphosphonate, bone, jaw},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1601-0825.2010.01778.x}
}
@ARTICLE{Wehrly2009,
author = {Wehrly, Tara D. and Chong, Audrey and Virtaneva, Kimmo and Sturdevant,
Dan E. and Child, Robert and Edwards, Jessica A. and Brouwer, Dedeke
and Nair, Vinod and Fischer, Elizabeth R. and Wicke, Luke and Curda,
Alissa J. and Kupko, John J. and Martens, Craig and Crane, Deborah
D. and Bosio, Catharine M. and Porcella, Stephen F. and Celli, Jean},
title = {Intracellular biology and virulence determinants of Francisella tularensis
revealed by transcriptional profiling inside macrophages},
journal = {Cellular Microbiology},
year = {2009},
volume = {11},
pages = {1128--1150},
number = {7},
abstract = {Summary The highly infectious bacterium Francisella tularensis is
a facultative intracellular pathogen, whose virulence requires proliferation
inside host cells, including macrophages. Here we have performed
a global transcriptional profiling of the highly virulent F. tularensis
ssp. tularensis Schu S4 strain during its intracellular cycle within
primary murine macrophages, to characterize its intracellular biology
and identify pathogenic determinants based on their intracellular
expression profiles. Phagocytosed bacteria rapidly responded to their
intracellular environment and subsequently altered their transcriptional
profile. Differential gene expression profiles were revealed that
correlated with specific intracellular locale of the bacteria. Upregulation
of general and oxidative stress response genes was a hallmark of
the early phagosomal and late endosomal stages, while induction of
transport and metabolic genes characterized the cytosolic replication
stage. Expression of the Francisella Pathogenicity Island (FPI) genes,
which are required for intracellular proliferation, increased during
the intracellular cycle. Similarly, 27 chromosomal loci encoding
putative hypothetical, secreted, outer membrane proteins or transcriptional
regulators were identified as upregulated. Among these, deletion
of FTT0383, FTT0369c or FTT1676 abolished the ability of Schu S4
to survive or proliferate intracellularly and cause lethality in
mice, therefore identifying novel determinants of Francisella virulence
from their intracellular expression profile.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2009.01316.x}
}
@ARTICLE{WeiYang2008,
author = {Wei Yang, Thomas Ju and Perry, Paula Jay and Ciani, Silvano and Pandian,
Sundaravel and Schmidt, Wolfgang},
title = {Manganese deficiency alters the patterning and development of root
hairs in Arabidopsis},
journal = {J. Exp. Bot.},
year = {2008},
volume = {59},
pages = {3453--3464},
number = {12},
month = sep,
abstract = {Manganese (Mn) is the second most prevalent transition metal in the
Earth's crust but its availability is often limited due to rapid
oxidation and low mobility of the oxidized forms. Acclimation to
low Mn availability was studied in Arabidopsis seedlings subjected
to Mn deficiency. As reported here, Mn deficiency caused a thorough
change in the arrangement and characteristics of the root epidermal
cells. A proportion of the extra hairs formed upon Mn deficiency
were located in atrichoblast positions, indicative of a post-embryonic
reprogramming of the cell fate acquired during embryogenesis. When
plants were grown under a light intensity of >50 {micro}mol m-2 s-1
in the presence of manganese root hair elongation was substantially
inhibited, whereas Mn-deficient seedlings displayed stimulated root
hair development. GeneChip analysis revealed several candidate genes
with potential roles in the reprogramming of rhizodermal cells. None
of the genes that function in epidermal cell fate specification were
affected by Mn deficiency, indicating that the patterning mechanism
which controls the differentiation of rhizodermal cells during embryogenesis
have been bypassed under Mn-deficient conditions. This assumption
is supported by the partial rescue of the hairless cpc mutant by
Mn deficiency. Inductively coupled plasma-optical emission spectroscopy
(ICP-OES) analysis revealed that, besides the anticipated reduction
in Mn concentration, Mn deficiency caused an increase in iron concentration.
This increase was associated with a decreased transcript level of
the iron transporter IRT1, indicative of a more efficient transport
of iron in the absence of Mn.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/59/12/3453}
}
@ARTICLE{Wei2005,
author = {Wei, Chia Lin and Miura, Takumi and Robson, Paul and Lim, Sai-Kiang
and Xu, Xiu-Qin and Lee, Mathia Yu-Chuan and Gupta, Sanjay and Stanton,
Lawrence and Luo, Yongquan and Schmitt, Jacqui and Thies, Scott and
Wang, Wei and Khrebtukova, Irina and Zhou, Daixing and Liu, Edison
T. and Ruan, Yi Jun and Rao, Mahendra and Lim, Bing},
title = {Transcriptome Profiling of Human and Murine ESCs Identifies Divergent
Paths Required to Maintain the Stem Cell State},
journal = {STEM CELLS},
year = {2005},
volume = {23},
pages = {166--185},
number = {2},
abstract = {Abstract 10.1634/stemcells.2004-0162.abs Human embryonic stem cells
(hESCs) are an important source of stem cells in regenerative medicine,
and much remains unknown about their molecular characteristics. To
develop a detailed genomic profile of ESC lines in two different
species, we compared transcriptomes of one murine and two different
hESC lines by massively parallel signature sequencing (MPSS). Over
2 million signature tags from each line and their differentiating
embryoid bodies were sequenced. Major differences and conserved similarities
between species identified by MPSS were validated by reverse transcription
polymerase chain reaction (RT-PCR) and microarray. The two hESC lines
were similar overall, with differences that are attributable to alleles
and propagation. Human–mouse comparisons, however, identified only
a small (core) set of conserved genes that included genes known to
be important in ESC biology, as well as additional novel genes. Identified
were major differences in leukemia inhibitory factor, transforming
growth factor-beta, and Wnt and fibroblast growth factor signaling
pathways, as well as the expression of genes encoding metabolic,
cytoskeletal, and matrix proteins, many of which were verified by
RT-PCR or by comparing them with published databases. The study reported
here underscores the importance of cross-species comparisons and
the versatility and sensitivity of MPSS as a powerful complement
to current array technology.},
issn = {1549-4918},
keywords = {Embryonic stem cells, murine and human, Transcriptome, Massively parallel
signature sequencing (MPSS)},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2004-0162}
}
@ARTICLE{Wei2004,
author = {Wei, Jun S. and Greer, Braden T. and Westermann, Frank and Steinberg,
Seth M. and Son, Chang-Gue and Chen, Qing-Rong and Whiteford, Craig
C. and Bilke, Sven and Krasnoselsky, Alexei L. and Cenacchi, Nicola
and Catchpoole, Daniel and Berthold, Frank and Schwab, Manfred and
Khan, Javed},
title = {Prediction of Clinical Outcome Using Gene Expression Profiling and
Artificial Neural Networks for Patients with Neuroblastoma},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {6883--6891},
number = {19},
month = oct,
abstract = {Currently, patients with neuroblastoma are classified into risk groups
(e.g., according to the Children's Oncology Group risk-stratification)
to guide physicians in the choice of the most appropriate therapy.
Despite this careful stratification, the survival rate for patients
with high-risk neuroblastoma remains <30%, and it is not possible
to predict which of these high-risk patients will survive or succumb
to the disease. Therefore, we have performed gene expression profiling
using cDNA microarrays containing 42,578 clones and used artificial
neural networks to develop an accurate predictor of survival for
each individual patient with neuroblastoma. Using principal component
analysis we found that neuroblastoma tumors exhibited inherent prognostic
specific gene expression profiles. Subsequent artificial neural network-based
prognosis prediction using expression levels of all 37,920 good-quality
clones achieved 88% accuracy. Moreover, using an artificial neural
network-based gene minimization strategy in a separate analysis we
identified 19 genes, including 2 prognostic markers reported previously,
MYCN and CD44, which correctly predicted outcome for 98% of these
patients. In addition, these 19 predictor genes were able to additionally
partition Children's Oncology Group-stratified high-risk patients
into two subgroups according to their survival status (P = 0.0005).
Our findings provide evidence of a gene expression signature that
can predict prognosis independent of currently known risk factors
and could assist physicians in the individual management of patients
with high-risk neuroblastoma.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/19/6883}
}
@ARTICLE{Wei2007,
author = {Wei, Qiang and Hebda-Bauer, Elaine K. and Pletsch, Amy and Luo, Jie
and Hoversten, Mary T. and Osetek, Andrew J. and Evans, Simon J.
and Watson, Stanley J. and Seasholtz, Audrey F. and Akil, Huda},
title = {Overexpressing the Glucocorticoid Receptor in Forebrain Causes an
Aging-Like Neuroendocrine Phenotype and Mild Cognitive Dysfunction},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {8836--8844},
number = {33},
month = aug,
abstract = {Repeated stress enhances vulnerability to neural dysfunction that
is cumulative over the course of the lifespan. This dysfunction contributes
to cognitive deficits observed during aging. In addition, aging is
associated with dysregulation of the limbic-hypothalamic-pituitary-adrenal
(LHPA) axis, leading to a delayed termination of the stress response.
This delay, in turn, increases exposure to glucocorticoids and exacerbates
the likelihood of neural damage. Here we asked whether similar effects
could emerge at an early age as a result of genetic variations in
the level or function of the brain glucocorticoid receptor (GR).
We investigated the effect of forebrain-specific overexpression of
GR on LHPA axis activity. Transgenic mice with GR overexpression
in forebrain (GRov) display normal basal circulating adrenocorticotropic
hormone and corticosterone levels. However, young GRov mice exhibit
a number of LHPA alterations, including a blunted initial response
to acute restraint stress followed by a delayed turn-off of the stress
response. This deficit in negative feedback is paradoxical in the
face of elevated GR levels, resembles the stress response in aged
animals, and continues to worsen as GRov mice age. The neuroendocrine
dysregulation in young GRov mice is coupled with a mild cognitive
deficit, also consistent with the accelerated aging hypothesis. The
molecular basis of this phenotype was examined using microarray analysis
of the hippocampus, which revealed a broad downregulation of glutamate
receptor signaling in GRov mice. Thus, even in the absence of chronic
stress, elevation of GR gene expression can lead to an increased
allostatic load and result in an "aging-like" phenotype in young
animals.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/33/8836}
}
@ARTICLE{Wei2010,
author = {Wei, Qingxiang and Levens, Eric D. and Stefansson, Lilja and Nieman,
Lynnette K.},
title = {Indian Hedgehog and Its Targets in Human Endometrium: Menstrual Cycle
Expression and Response to CDB-2914},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {5330--5337},
number = {12},
month = dec,
abstract = {Context: Progesterone is critical for secretory endometrial differentiation
in women, but its downstream mediators are poorly understood. Objective:
Our objective was to investigate endometrial expression of Indian
Hedgehog (IHH) and genes involved in its signaling [smoothened (SMO),
patched-1 (PTCH1), glioma-associated oncogene homolog 1 (GLI1), and
GLI2] during the menstrual cycle and the effects of the selective
progesterone receptor modulator CDB-2914 on its expression. Design
and Setting: Comparisons between normally cycling volunteers and
women with symptomatic fibroids who received CDB-2914 or placebo
were made at a clinical research center. Patients and Interventions:
Endometrial biopsy was performed on 34 volunteers, 17 additional
women with fibroids. Main Outcome Measures: Endometrial expression
of IHH, SMO, PTCH1, GLI1, and GLI2 by in situ hybridization and/or
RT-PCR and IHH, GLI1, and PTCH1 immunohistochemistry were evaluated.
Results: RT-PCR showed expression of IHH, SMO, PTCH1, GLI1, and GLI2,
with significant increases in IHH (5.2-fold) and GLI1 (3.6-fold)
in endometrium exposed to CDB-2914 compared with placebo. In situ
hybridization showed IHH mRNA expression in glands and stroma that
was stronger in secretory samples. Among volunteers, IHH and GLI1
immunohistochemistry scores were higher in the secretory than proliferative
phase in the nuclei and cytoplasm of glands and stroma (P = 0.0002-0.04).
Compared with follicular-phase controls, women exposed to CDB-2914
showed increased IHH expression in all compartments except stromal
cytoplasm (P = 0.0199-0.0423); GLI1 was up-regulated in glandular
nuclei and cytoplasm compared with both volunteers and women receiving
placebo (P [≤] 0.0416). Conclusions: The temporal increase in
endometrial IHH and GLI1 during the secretory phase, and their modulation
by CDB-2914, suggests progestin regulation and a potential role in
endometrial differentiation and implantation.},
comment = {10.1210/jc.2010-0637},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/12/5330}
}
@ARTICLE{Wei2008,
author = {Wei, Shuanzeng and Dunn, Thomas A. and Isaacs, William B. and De
Marzo, Angelo M. and Luo, Jun},
title = {GOLPH2 and MYO6: Putative prostate cancer markers localized to the
Golgi apparatus},
journal = {Prostate},
year = {2008},
volume = {68},
pages = {1387--1395},
number = {13},
abstract = {Abstract 10.1002/pros.20806.abs BACKGROUND Malignant transformation
is often accompanied by morphological and functional alterations
in subcellular organelles. The Golgi apparatus is a subcellular structure
primarily involved in modification and sorting of macromolecules
for secretion and transport to other cellular destinations. Molecular
alterations associated with the Golgi apparatus may take place during
prostate carcinogenesis but such alterations have not been documented.
METHODS To demonstrate that the Golgi apparatus undergoes alterations
during prostate carcinogenesis, we examined the expression and localization
of two candidate molecules, Golgi phosphoprotein 2 (GOLPH2) and myosin
VI (MYO6), both overexpressed in prostate cancer as initially identified
by expression microarray analysis. RESULTS Elevated GOLPH2 expression
in prostate cancers was validated through real-time RT-PCR, Western
blot, and tissue microarray analysis, and its Golgi localization
in surgical prostate cancer tissues confirmed using two-color immunofluorescence.
In addition, distinctive juxtanuclear MYO6 staining pattern consistent
with Golgi localization was observed in surgical prostate cancer
tissues. Two-color immunofluorescence revealed intensive Golgi-specific
staining for both GOLPH2 and myosin VI in prostate cancer cells but
not in the adjacent normal prostate epithelium. CONCLUSIONS We show
that the Golgi apparatus in prostate cancer cells differs from the
normal Golgi by elevated levels of two molecules, GOLPH2 and MYO6.
These results for the first time demonstrated consistent cancer cell-specific
alterations in the molecular composition of the Golgi apparatus.
Such alterations can be explored for discovery of novel prostate
cancer biomarkers through targeted organellar approaches. Prostate
68: 1387–1395, 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {prostate cancer, GOLPH2, myosin VI, Golgi},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20806}
}
@ARTICLE{Wei2011a,
author = {Wei, Wenliang and Qi, Xiaoqiong and Wang, Linhai and Zhang, Yanxin
and Hua, Wei and Li, Donghua and Lv, Haixia and Zhang, Xiurong},
title = {Characterization of the sesame (Sesamum indicum L.) global transcriptome
using Illumina paired-end sequencing and development of EST-SSR markers},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {451},
number = {1},
abstract = {BACKGROUND:Sesame is an important oil crop, but limited transcriptomic
and genomic data are currently available. This information is essential
to clarify the fatty acid and lignan biosynthesis molecular mechanism.
In addition, a shortage of sesame molecular markers limits the efficiency
and accuracy of genetic breeding. High-throughput transcriptomic
sequencing is essential to generate a large transcriptome sequence
dataset for gene discovery and molecular marker development.RESULTS:Sesame
transcriptomes from five tissues were sequenced using Illumina paired-end
sequencing technology. The cleaned raw reads were assembled into
a total of 86,222 unigenes with an average length of 629 bp. Of the
unigenes, 46,584 (54.03%) had significant similarity with proteins
in the NCBI nonredundant protein database and Swiss-Prot database
(E-value < 10-5). Of these annotated unigenes, 10,805 and 27,588
unigenes were assigned to gene ontology categories and clusters of
orthologous groups, respectively. In total, 22,003 (25.52%) unigenes
were mapped onto 119 pathways using the Kyoto Encyclopedia of Genes
and Genomes Pathway database (KEGG). Furthermore, 44,750 unigenes
showed homology to 15,460 Arabidopsis genes based on BLASTx analysis
against The Arabidopsis Information Resource (TAIR, Version 10) and
revealed relatively high gene coverage. In total, 7,702 unigenes
were converted into SSR markers (EST-SSR). Dinucleotide SSRs were
the dominant repeat motif (67.07%, 5,166), followed by trinucleotide
(24.89%, 1,917), tetranucleotide (4.31%, 332), hexanucleotide (2.62%,
202), and pentanucleotide (1.10%, 85) SSRs. AG/CT (46.29%) was the
dominant repeat motif, followed by AC/GT (16.07%), AT/AT (10.53%),
AAG/CTT (6.23%), and AGG/CCT (3.39%). Fifty EST-SSRs were randomly
selected to validate amplification and to determine the degree of
polymorphism in the genomic DNA pools. Forty primer pairs successfully
amplified DNA fragments and detected significant amounts of polymorphism
among 24 sesame accessions.CONCLUSIONS:This study demonstrates that
Illumina paired-end sequencing is a fast and cost-effective approach
to gene discovery and molecular marker development in non-model organisms.
Our results provide a comprehensive sequence resource for sesame
research.},
doi = {10.1186/1471-2164-12-451},
issn = {1471-2164},
pubmedid = {21929789},
url = {http://www.biomedcentral.com/1471-2164/12/451}
}
@ARTICLE{Wei2007a,
author = {Wei, Wu and Wang, Weihua and Cao, Zhiwei and Yu, Hong and Wang, Xiaojing
and Zhao, Jing and Tan, Hao and Xu, Hao and Jiang, Weihong and Li,
Yixue},
title = {Comparative Analysis of Two-component Signal Transduction System
in Two Streptomycete Genomes},
journal = {Acta Biochim Biophys Sin},
year = {2007},
volume = {39},
pages = {317--325},
number = {5},
month = may,
abstract = {Species of the genus Streptomyces are major bacteria responsible for
producing most natural antibiotics. Streptomyces coelicolor A3(2)
and Streptomyces avermitilis were sequenced in 2002 and 2003, respectively.
Two-component signal transduction systems (TCSs), consisting of a
histidine sensor kinase (SK) and a cognate response regulator (RR),
form the most common mechanism of transmembrane signal transduction
in prokaryotes. TCSs in S. coelicolor A3(2) have been analyzed in
detail. Here, we identify and classify the SK and RR of S. avermitilis
and compare the TCSs with those of S. coelicolor A3(2) by computational
approaches. Phylogenetic analysis of the cognate SK-RR pairs of the
two species indicated that the cognate SK-RR pairs fall into four
classes according to the distribution of their orthologs in other
organisms. In addition to the cognate SK-RR pairs, some potential
partners of non-cognate SK-RR were found, including those of unpaired
SK and orphan RR and the cross-talk between different components
in either strain. Our study provides new clues for further exploration
of the molecular regulation mechanism of streptomycetes with industrial
importance.},
url = {http://abbs.oxfordjournals.org/cgi/content/abstract/39/5/317}
}
@ARTICLE{Wei2011,
author = {Wei, Xiaomu and Walia, Vijay and Lin, Jimmy C and Teer, Jamie K and
Prickett, Todd D and Gartner, Jared and Davis, Sean and Stemke-Hale,
Katherine and Davies, Michael A and Gershenwald, Jeffrey E and Robinson,
William and Robinson, Steven and Rosenberg, Steven A and Samuels,
Yardena},
title = {Exome sequencing identifies GRIN2A as frequently mutated in melanoma},
journal = {Nat Genet},
year = {2011},
volume = {43},
pages = {442--446},
number = {5},
month = may,
comment = {10.1038/ng.810},
issn = {1061-4036},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/ng.810}
}
@ARTICLE{Wei2009,
author = {Wei, Yuanyuan and Chen, Shuang and Yang, Pengcheng and Ma, Zongyuan
and Kang, Le},
title = {Characterization and comparative profiling of the small RNA transcriptomes
in two phases of locust},
journal = {Genome Biology},
year = {2009},
volume = {10},
pages = {R6},
number = {1},
abstract = {BACKGROUND:All the reports on insect small RNAs come from holometabolous
insects whose genome sequence data are available. Therefore, study
of hemimetabolous insect small RNAs could provide more insights into
evolution and function of small RNAs in insects. The locust is an
important, economically harmful hemimetabolous insect. Its phase
changes, as a phenotypic plasticity, result from differential gene
expression potentially regulated at both the post-transcriptional
level, mediated by small RNAs, and the transcriptional level.RESULTS:Here,
using high-throughput sequencing, we characterize the small RNA transcriptome
in the locust. We identified 50 conserved microRNA families by similarity
searching against miRBase, and a maximum of 185 potential locust-specific
microRNA family candidates were identified using our newly developed
method independent of locust genome sequence. We also demonstrate
conservation of microRNA*, and evolutionary analysis of locust microRNAs
indicates that the generation of miRNAs in locusts is concentrated
along three phylogenetic tree branches: bilaterians, coelomates,
and insects. Our study identified thousands of endogenous small interfering
RNAs, some of which were of transposon origin, and also detected
many Piwi-interacting RNA-like small RNAs. Comparison of small RNA
expression patterns of the two phases showed that longer small RNAs
were expressed more abundantly in the solitary phase and that each
category of small RNAs exhibited different expression profiles between
the two phases.CONCLUSIONS:The abundance of small RNAs in the locust
might indicate a long evolutionary history of post-transcriptional
gene expression regulation, and differential expression of small
RNAs between the two phases might further disclose the molecular
mechanism of phase changes.},
doi = {10.1186/gb-2009-10-1-r6},
issn = {1465-6906},
pubmedid = {19146710},
url = {http://genomebiology.com/2009/10/1/R6}
}
@ARTICLE{Wei2004a,
author = {Wei, Yu-Dan and Tepperman, Katherine and Huang, Ming-ya and Sartor,
Maureen A. and Puga, Alvaro},
title = {Chromium Inhibits Transcription from Polycyclic Aromatic Hydrocarbon-inducible
Promoters by Blocking the Release of Histone Deacetylase and Preventing
the Binding of p300 to Chromatin},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {4110--4119},
number = {6},
month = feb,
abstract = {Co-contamination with complex mixtures of carcinogenic metals, such
as chromium, and polycyclic aromatic hydrocarbons is a common environmental
problem with multiple biological consequences. Chromium exposure
alters inducible gene expression, forms chromium-DNA adducts and
chromium-DNA cross-links, and disrupts transcriptional activator-co-activator
complexes. We have shown previously that exposure of mouse hepatoma
Hepa-1 cells to chromate inhibits the induction of the Cyp1a1 and
Nqo1 genes by dioxin. Here we have tested the hypothesis that chromium
blocks gene expression by interfering with the assembly of productive
transcriptional complexes at the promoter of inducible genes. To
this end, we have studied the effects of chromium on the expression
of genes induced by benzo[a]pyrene (B[a]P), another aryl hydrocarbon
receptor agonist, and characterized the disruption of Cyp1a1 transcriptional
induction by chromium. Gene expression profiling by using high density
microarray analysis revealed that the inhibitory effect of chromium
on B[a]P-dependent gene induction was generalized, affecting the
induction of over 50 different genes involved in a variety of signaling
transduction pathways. The inhibitory effect of chromium on Cyp1a1
transcription was found to depend on the presence of promoter-proximal
sequences and not on the cis-acting enhancer sequences that bind
the aryl hydrocarbon receptor-aryl hydrocarbon receptor nuclear translocator
complex. By using transient reporter assays and chromatin immunoprecipitation
analyses, we found that chromium prevented the B[a]P-dependent release
of HDAC-1 from Cyp1a1 chromatin and blocked p300 recruitment. These
results provide a mechanistic explanation for the observation that
chromium inhibits inducible but not constitutive gene expression.},
url = {http://www.jbc.org/cgi/content/abstract/279/6/4110}
}
@ARTICLE{Weibel2011,
author = {Weibel, Stephanie and Raab, Viktoria and Yu, Yong and Worschech,
Andrea and Wang, Ena and Marincola, Francesco and Szalay, Aladar},
title = {Viral-mediated oncolysis is the most critical factor in the late-phase
of the tumor regression process upon vaccinia virus infection},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {68},
number = {1},
abstract = {BACKGROUND:In principle, the elimination of malignancies by oncolytic
virotherapy could proceed by different mechanisms - e.g. tumor cell
specific oncolysis, destruction of the tumor vasculature or an anti-tumoral
immunological response. In this study, we analyzed the contribution
of these factors to elucidate the responsible mechanism for regression
of human breast tumor xenografts upon colonization with an attenuated
vaccinia virus (VACV).METHODS:Breast tumor xenografts were analyzed
6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry
and mouse-specific expression arrays. Viral-mediated oncolysis was
determined by tumor growth analysis combined with microscopic studies
of intratumoral virus distribution. The tumor vasculature was morphologically
characterized by diameter and density measurements and vessel functionality
was analyzed by lectin perfusion and extravasation studies. Immunological
aspects of viral-mediated tumor regression were studied in either
immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon
cyclophosphamide-induced immunosuppression (MHCII+-cell depletion)
in nude mice.RESULTS:Late stage VACV-infected breast tumors showed
extensive necrosis, which was highly specific to cancer cells. The
tumor vasculature in infected tumor areas remained functional and
the endothelial cells were not infected. However, viral colonization
triggers hyperpermeability and dilatation of the tumor vessels, which
resembled the activated endothelium in wounded tissue. Moreover,
we demonstrated an increased expression of genes involved in leukocyte-endothelial
cell interaction in VACV-infected tumors, which orchestrate perivascular
inflammatory cell infiltration. The immunohistochemical analysis
of infected tumors displayed intense infiltration of MHCII-positive
cells and colocalization of tumor vessels with MHCII+/CD31+ vascular
leukocytes. However, GI-101A tumor growth analysis upon VACV-infection
in either immunosuppressed nude mice (MHCII+-cell depleted) or in
immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed
that neither MHCII-positive immune cells nor T-, B-, or NK cells
contributed significantly to VACV-mediated tumor regression. In contrast,
tumors of immunosuppressed mice showed enhanced viral spreading and
tumor necrosis.CONCLUSIONS:Taken together, these results indicate
that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage
in the late regression phase. Neither the destruction of the tumor
vasculature nor the massive VACV-mediated intratumoral inflammation
was a prerequisite for tumor regression. We propose that approaches
to enhance viral replication and spread within the tumor microenvironment
should improve therapeutical outcome.},
doi = {10.1186/1471-2407-11-68},
issn = {1471-2407},
pubmedid = {21320309},
url = {http://www.biomedcentral.com/1471-2407/11/68}
}
@ARTICLE{Weichert2010,
author = {Weichert, Nicola and Saalbach, Isolde and Weichert, Heiko and Kohl,
Stefan and Erban, Alexander and Kopka, Joachim and Hause, Bettina
and Varshney, Alok and Sreenivasulu, Nese and Strickert, Marc and
Kumlehn, Jochen and Weschke, Winfriede and Weber, Hans},
title = {Increasing Sucrose Uptake Capacity of Wheat Grains Stimulates Storage
Protein Synthesis},
journal = {Plant Physiology},
year = {2010},
volume = {152},
pages = {698--710},
number = {2},
month = feb,
abstract = {Increasing grain sink strength by improving assimilate uptake capacity
could be a promising approach toward getting higher yield. The barley
(Hordeum vulgare) sucrose transporter HvSUT1 (SUT) was expressed
under control of the endosperm-specific Hordein B1 promoter (HO).
Compared with the wild type, transgenic HOSUT grains take up more
sucrose (Suc) in vitro, showing that the transgene is functional.
Grain Suc levels are not altered, indicating that Suc fluxes are
influenced rather than steady-state levels. HOSUT grains have increased
percentages of total nitrogen and prolamins, which is reflected in
increased levels of phenylalanine, tyrosine, tryptophan, isoleucine,
and leucine at late grain development. Transcript profiling indicates
specific stimulation of prolamin gene expression at the onset of
storage phase. Changes in gene expression and metabolite levels related
to carbon metabolism and amino acid biosynthesis suggest deregulated
carbon-nitrogen balance, which together indicate carbon sufficiency
and relative depletion of nitrogen. Genes, deregulated together with
prolamin genes, might represent candidates, which respond positively
to assimilate supply and are related to sugar-starch metabolism,
cytokinin and brassinosteroid functions, cell proliferation, and
sugar/abscisic acid signaling. Genes showing inverse expression patterns
represent potential negative regulators. It is concluded that HvSUT1
overexpression increases grain protein content but also deregulates
the metabolic status of wheat (Triticum aestivum) grains, accompanied
by up-regulated gene expression of positive and negative regulators
related to sugar signaling and assimilate supply. In HOSUT grains,
alternating stimulation of positive and negative regulators causes
oscillatory patterns of gene expression and highlights the capacity
and great flexibility to adjust wheat grain storage metabolism in
response to metabolic alterations.},
url = {http://www.plantphysiol.org/cgi/content/abstract/152/2/698}
}
@ARTICLE{Weidenfeld-Baranboim2009,
author = {Weidenfeld-Baranboim, Keren and Hasin, Tal and Darlyuk, Ilona and
Heinrich, Ronit and Elhanani, Ofer and Pan, Jianzhi and Yokoyama,
Kazunari K. and Aronheim, Ami},
title = {The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription
of its homologue immediate early gene counterpart, ATF3},
journal = {Nucleic Acids Res.},
year = {2009},
volume = {37},
pages = {2194--2203},
number = {7},
month = apr,
abstract = {JDP2 is a ubiquitously expressed bZIP repressor protein. JDP2 binds
TPA response element and cyclic AMP response element located within
various promoters. JDP2 displays a high degree of homology to the
immediate early gene ATF3. ATF3 plays a crucial role in the cellular
adaptive response to multiple stress insults as well as growth stimuli.
We have identified ATF3 as a potential target gene for JDP2 repression.
JDP2 regulates the ATF3 promoter potentially through binding to both
the consensus ATF/CRE site and a non-consensus ATF3 auto-repression
DNA-binding element. Expression of ATF3 protein in wild-type mouse
embryo fibroblast (MEF) cells is below the detectable levels, whereas,
JDP2 disrupted MEF cells display noticeable level of ATF3 protein.
Following either serum or ER stress stimulation, ATF3 expression
is potentiated in JDP2-KO fibroblast cells as compared with wild-type
cells. Mice with either JDP2 over-expression or JDP2 disruption display
undetectable level of ATF3 protein. However, ATF3 induction in response
to either growth or stress signals is dependent on JDP2 expression
level. ATF3 induction is attenuated in JDP2 over-expressing mice
whereas is potentiated in JDP2-KO mice as compared with the corresponding
wild-type mice. Collectively, the data presented strongly suggest
that JDP2 plays a role in the determination of the ATF3 adaptive
cellular threshold response to different stress insults and growth
stimuli.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/37/7/2194}
}
@ARTICLE{Weidhaas2009,
author = {Weidhaas, Joanne B. and Li, Shu-Xia and Winter, Kathryn and Ryu,
Janice and Jhingran, Anuja and Miller, Bridgette and Dicker, Adam
P. and Gaffney, David},
title = {Changes in Gene Expression Predicting Local Control in Cervical Cancer:
Results from Radiation Therapy Oncology Group 0128},
journal = {Clin. Cancer Res.},
year = {2009},
volume = {15},
pages = {4199--4206},
number = {12},
month = jun,
abstract = {Purpose: To evaluate the potential of gene expression signatures to
predict response to treatment in locally advanced cervical cancer
treated with definitive chemotherapy and radiation. Experimental
Design: Tissue biopsies were collected from patients participating
in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial
evaluating the benefit of celecoxib in addition to cisplatin chemotherapy
and radiation for locally advanced cervical cancer. Gene expression
profiling was done and signatures of pretreatment, mid-treatment
(before the first implant), and "changed" gene expression patterns
between pre- and mid-treatment samples were determined. The ability
of the gene signatures to predict local control versus local failure
was evaluated. Two-group t test was done to identify the initial
gene set separating these end points. Supervised classification methods
were used to enrich the gene sets. The results were further validated
by leave-one-out and 2-fold cross-validation. Results: Twenty-two
patients had suitable material from pretreatment samples for analysis,
and 13 paired pre- and mid-treatment samples were obtained. The changed
gene expression signatures between the pre- and mid-treatment biopsies
predicted response to treatment, separating patients with local failures
from those who achieved local control with a seven-gene signature.
The in-sample prediction rate, leave-one-out prediction rate, and
2-fold prediction rate are 100% for this seven-gene signature. This
signature was enriched for cell cycle genes. Conclusions: Changed
gene expression signatures during therapy in cervical cancer can
predict outcome as measured by local control. After further validation,
such findings could be applied to direct additional therapy for cervical
cancer patients treated with chemotherapy and radiation.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/12/4199}
}
@ARTICLE{Weigelt2007,
author = {Weigelt, Karin and Ernst, Wolfgang and Walczak, Yana and Ebert, Stefanie
and Loenhardt, Thomas and Klug, Maja and Rehli, Michael and Weber,
Bernhard H. F. and Langmann, Thomas},
title = {Dap12 expression in activated microglia from retinoschisin-deficient
retina and its PU.1-dependent promoter regulation},
journal = {J. Leukoc. Biol.},
year = {2007},
volume = {82},
pages = {1564--1574},
number = {6},
month = dec,
abstract = {Several alterations in the expression of immune-related transcripts
were identified recently in the degenerating retina of the retinoschisin
knockout (Rs1h-/Y) mouse, including the strong expression of the
adaptor protein Dap12. As Dap12 is found in leukocytes, we hypothesized
that its disease-related expression may be confined to activated
retinal microglia cells. To test this hypothesis, we established
a procedure for isolation and culture of retinal microglia cells
and performed genome-wide expression profiling from Rs1h-/Y and control
microglia. While retaining their activated state in culture, ex vivo
microglia expressed high levels of Dap12 and the transcription factor
PU.1. The activation-dependent induction of Dap12 was also confirmed
in the microglia cell line BV-2 following in vitro stimulation. To
examine the transcriptional regulation of Dap12 further, macrophage
cell lines were transfected with several Dap12 reporter constructs.
Promoter deletion assays and site-directed mutagenesis experiments
demonstrated an essential role of evolutionarily conserved PU.1 consensus
sites in the proximal -104/+118 Dap12 promoter. In vitro and in vivo
binding of PU.1 to this promoter region was demonstrated using EMSA
and chromatin immunoprecipitation. Knockdown of PU.1 by RNA interference
caused a significant reduction of endogenous Dap12 expression and
re-expression, and activation of PU.1 in PU.1-/- progenitor cells
induced Dap12 transcription. Taken together, our results indicate
that activated microglia from degenerating retinae express high levels
of Dap12 and PU.1, and PU.1 controls the myeloid-specific regulation
of Dap12 directly and may also play a general role in microglia gene
expression during retinal degeneration.},
url = {http://www.jleukbio.org/cgi/content/abstract/82/6/1564}
}
@ARTICLE{Weigelt2009,
author = {Weigelt, Karin and Lichtinger, Monika and Rehli, Michael and Langmann,
Thomas},
title = {Transcriptomic profiling identifies a PU.1 regulatory network in
macrophages},
journal = {Biochemical and Biophysical Research Communications},
year = {2009},
volume = {380},
pages = {308--312},
number = {2},
month = mar,
abstract = {PU.1 is a key transcription factor for hematopoiesis and macrophage
differentiation. Using chromatin immunoprecipitation we have previously
identified several PU.1 target genes in macrophages and microglia.
With the aim to complement these studies, we performed a transcriptomic
analysis of PU.1-/- progenitors after restoration of PU.1 activity.
PUER cells committed to macrophage differentiation were analyzed
with novel Affymetrix exon 1.0 ST arrays and Affymetrix 430 2.0 genome
arrays for crosswise validation. We combined these genome-wide expression
data with a publicly-available microarray dataset of PU.1-knockdown
hematopoietic stem cells for an integrated analysis. Bibliographic
gene connections, binding site prediction and ChIP-Chip data were
used to define a multi-level PU.1 regulatory network in macrophages.
Moreover, an alternative transcript of the novel PU.1 target gene
Ptpro was identified by exon arrays and PU.1 binding to an intronic
promoter was demonstrated. In conclusion, we present a PU.1 transcriptional
network with novel validated PU.1 target genes.},
issn = {0006-291X},
keywords = {PU.1, Macrophage differentiation, Exon arrays, ChIP-Chip, PUER cells,
Ptpro, Regulatory network},
url = {http://www.sciencedirect.com/science/article/B6WBK-4VF4SCX-N/2/154d4eaf2a1be746374bf7f9a82eeb53}
}
@BOOK{Weigl2007,
title = {Practical Aspects of Microfluidic Devices: Moving Fluids and Building
Devices},
publisher = {John Wiley \& Sons, Ltd},
year = {2007},
author = {Weigl, Bernhard H. and Bardell, Ron L. and Cabrera, Catherine},
pages = {--},
abstract = {This chapter provides insight into practical aspects of microfluidic
device design, such as fluid movement, device construction, and feature
integration. Several methods of moving fluids into and within microfluidic
devices are described, including batch-flow and continuous-flow micropumps,
electrokinetic pumps, and external positive displacement pumps. Solutions
for the problem of interfacing external fluid sources with a microfluidic
device are given. Then, various methods for the construction of microfluidic
devices are discussed, such as photolithography, soft lithography,
and laminate-based designs. Finally, as a case study, the integration
of a microfluidic device for the detection of pathogens is described.},
booktitle = {Handbook of Biosensors and Biochips},
issn = {9780470061565},
keywords = {microfluidics, bioMEMS, lab on a chip, micropump, photolithography,
soft lithography, laser ablation, machining, plastic-film laminates,
flow sensor},
url = {http://dx.doi.org/10.1002/9780470061565.hbb156}
}
@ARTICLE{WEIJERS2010,
author = {WEIJERS, E. M. and VAN WIJHE, M. H. and JOOSTEN, L. and HORREVOETS,
A. J. G. and DE MAAT, M. P. M. and VAN HINSBERGH, V. W. M. and KOOLWIJK,
P.},
title = {Molecular weight fibrinogen variants alter gene expression and functional
characteristics of human endothelial cells},
journal = {Journal of Thrombosis and Haemostasis},
year = {2010},
volume = {8},
pages = {2800--2809},
number = {12},
abstract = {Summary. Background: Fibrin is a temporary matrix that not only
seals a wound, but also provides a temporary matrix structure for
invading cells during wound healing. Two naturally occurring fibrinogen
variants, high molecular weight (HMW) and low molecular weight (LMW)
fibrinogen, display different properties in supporting angiogenesis
in vivo and in vitro. Objectives: This study was aimed at investigating
the functional characteristics and molecular mechanisms of human
microvascular endothelial cells (HMVECs) cultured on HMW and LMW
fibrin matrices. Methods and results: HMVECs on HMW fibrin matrices
showed increased proliferation and tube formation as compared with
their counterparts on unfractionated and LMW fibrin. Degradation
of HMW fibrin was markedly enhanced by the presence of HMVECs, that
of LMW fibrin was enhanced only slightly. However, the expression
levels of fibrinolysis-regulating proteins and integrins were similar.
Subsequent microarray analysis revealed that the expression of 377
genes differed significantly between HMVECs cultured on HMW fibrin
and those cultured on LMW fibrin. Among these genes, UNC5B, DLL4
and the DLL4–Notch downstream targets Hey1, Hey2 and Hes1 showed
increased expression in HMVECs on LMW fibrin. However, pharmacologic
and genetic (DLL4 small interfering RNA) inhibition of DLL4–Notch
signaling blunted rather than enhanced proliferation and tube formation
by HMVECs on both fibrin variants. Conclusions: Heterogeneity in
naturally occurring fibrinogen strongly influences endothelial cell
proliferation and tube formation, and causes alterations in gene
expression, including that of DLL4–Notch. The higher fibrinolytic
sensitivity of HMW fibrin in the presence of HMVECs contributes to
increased tube formation. Although the expression of DLL4–Notch
was altered, it did not explain the enhanced tube formation in HMW
fibrin. This study provides new perspectives for biological and tissue
engineering applications.},
doi = {10.1111/j.1538-7836.2010.04096.x},
issn = {1538-7836},
keywords = {angiogenesis, DLL4, endothelial cell, fibrin, fibrinogen, microarray},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1538-7836.2010.04096.x}
}
@ARTICLE{Weikert2005,
author = {Weikert, Steffen and Christoph, Frank and Schrader, Mark and Krause,
Hans and Miller, Kurt and Müller, Markus},
title = {Quantitative analysis of survivin mRNA expression in urine and tumor
tissue of bladder cancer patients and its potential relevance for
disease detection and prognosis},
journal = {Int. J. Cancer},
year = {2005},
volume = {116},
pages = {100--104},
number = {1},
abstract = {Abstract 10.1002/ijc.21000.abs Suppression of apoptosis may favor
the onset and progression of cancer. Survivin is an inhibitor of
apoptosis that has been suggested as a novel diagnostic/prognostic
marker of bladder cancer. In this study, survivin mRNA expression
was measured by a sensitive real-time PCR assay in tumor tissue and
urine from bladder cancer patients and assessed for its potential
diagnostic and prognostic relevance. Specimens from 53 patients with
bladder transitional cell carcinoma (TCC) were analyzed, the controls
being normal urothelial tissues (n = 14) and urine from benign disease
patients (n = 22) and healthy individuals (n = 14). Survivin transcripts
were commonly detected in tumor tissues, but not in normal urothelium,
and increasing mRNA levels correlate with progressing pathologic
stage (p = 0.001) and grade categories (p < 0.004). Higher levels
of expression were associated with a reduced time to recurrence in
noninvasive TCCs (p = 0.027, log-rank test) and a trend toward shorter
disease-free survival in muscle-invasive tumors (p = 0.067). Urinary
survivin analysis detects TCC with higher sensitivity (68.6%) and
equal specificity (100%) when compared with cytology (31.4% and 97.1%).
Our results indicate that tissue levels of survivin mRNA predict
disease-free survival in noninvasive TCC and may have a role in bladder
cancer progression. When analyzed by RT-PCR in urine, survivin is
a highly specific biomarker for TCC detection. © 2005 Wiley-Liss,
Inc.},
issn = {1097-0215},
keywords = {apoptosis, bladder cancer, cytology, survivin},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.21000}
}
@ARTICLE{Weikert2006,
author = {Weikert, Steffen and Christoph, Frank and Schulze, Wolfgang and Krause,
Hans and Kempkensteffen, Carsten and Schostak, Martin and Miller,
Kurt and Schrader, Mark},
title = {Testicular expression of survivin and human telomerase reverse transcriptase
(hTERT) associated with spermatogenic function in infertile patients},
journal = {Asian Journal of Andrology},
year = {2006},
volume = {8},
pages = {95--100},
number = {1},
abstract = {Abstract Aim: To characterize the coexpression of survivin, an inhibitor
of apoptosis (IAF), and human telomerase reverse transcriptase (hTERT)
in human testes with varying spermatogenic function. Methods: Transcript
levels of survivin mRNA and hTERT mRNA were determined in normal
testes (n= 11) and testes with defective spermatogenesis (n= 28)
using real-time reverse-transcription polymerase chain reaction (RT-PCR).
The histological work-up was performed according to a modified Johnsen
score. Results: Expressions of both survivin and hTERT were highest
at median levels of 96.8 and 709 in normal spermatogenesis and dropped
to 53.3 and 534 in testes with postmeiotic spermatogenic arrest (n=
10). In severe spermatogenic failure (n= 18), survivin expression
was lacking in most specimens (n = 16), whereas at least low levels
of testicular hTERT expression were largely detectable with a normalized
expression of 73 in premeiotic spermatogenic arrest (n= 7) and 45
in patients with Sertoli cell-only syndrome (SCOS) (n= 3). Both survivin
and hTERT expressions increased with a progressing Johnsen score
(P for trend = 0.001). Conclusion: Although both survivin and hTERT
are correlated with spermatogenic function, they show different expression
patterns in testes of infertile patients. These findings substantiate
results from studies in the rodent testis suggesting a predominant
expression of survivin in meiotically dividing germ cells.},
issn = {1745-7262},
keywords = {survivin, human telomerase reverse transcriptase, apoptosis, azoospermia,
male infertility, spermatogenesis},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1745-7262.2006.00102.x}
}
@ARTICLE{WEIKERT2005,
author = {WEIKERT, STEFFEN and SCHRADER, MARK and CHRISTOPH, FRANK and SCHULZE,
WOLFGANG and KRAUSE, HANS and MÃœLLER, MARKUS and MILLER, KURT},
title = {Quantification of survivin mRNA in testes of infertile patients and
in testicular germ cell tumours: high levels of expression associated
with normal spermatogenesis},
journal = {International Journal of Andrology},
year = {2005},
volume = {28},
pages = {224--229},
number = {4},
abstract = {Summary Deregulated apoptosis of germ cells may contribute to male
infertility as well as malignant transformation. Survivin, an inhibitor
of apoptosis (IAP), is overexpressed in all the most common human
malignancies, but barely detectable in normal tissues. We used real-time
polymerase chain reaction (PCR) to quantify survivin mRNA expression
in normal testes (n = 22), testes with defective spermatogenesis
(n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin
was expressed at high levels in normal testes. Testicular survivin
levels in infertile patients were related inversely to the severity
of spermatogenic failure (p < 0.001), with a lack of expression
in most specimens with pre-meiotic spermatogenic arrest and in all
those with germ cell aplasia. Lower levels of expression were observed
in TGCTs than in normal testes. While survivin expression was detected
in most TGCTs with undifferentiated components (12 of 13), it was
absent in all mature teratomas (n = 3). These data show that survivin
is expressed in normal and transformed germ cells. Its downregulation
in spermatogenic disorders indicates that survivin may contribute
to the normal balance between germ cell proliferation and apoptosis.
In TGCTs, survivin expression appears to be lost with somatic differentiation.},
issn = {1365-2605},
keywords = {apoptosis, male infertility, spermatogenesis, survivin, testicular
cancer},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2605.2005.00549.x}
}
@ARTICLE{Weikert2005a,
author = {Weikert, Steffen and Schrader, Mark and Müller, Markus and Schulze,
Wolfgang and Krause, Hans and Miller, Kurt},
title = {Expression levels of the inhibitor of apoptosis survivin in testes
of patients with normal spermatogenesis and spermatogenic failure},
journal = {Fertility and Sterility},
year = {2005},
volume = {83},
pages = {1100--1105},
number = {4, Supplement 1},
month = apr,
abstract = {Objective To determine the expression of the inhibitor of apoptosis
survivin in men with and without spermatogenic failure.Design Prospective
case study.Setting Two university-based infertility clinics.Patient(s)
Forty-nine infertile men presenting with azoospermia.Intervention(s)
Testicular biopsies for histopathological assessment and analyses
of survivin expression levels by real-time reverse transcription-polymerase
chain reaction. Survivin levels were normalized to expression of
the housekeeping porphobilinogen deaminase gene.Main Outcome Measure(s)
Correlation of the histological findings with normalized survivin
expression levels.Results(s) Testicular survivin mRNA expression
was highest in normal spermatogenesis (n = 14). Decreased expression
was observed in patients with spermatogenesis disorders. The expression
level correlated with the degree of spermatogenic failure. While
it was reduced in postmeiotic maturation arrest (n = 11), a lack
of expression was seen in most specimens (10 of 12) with premeiotic
maturation arrest and in all of those with Sertoli cell-only syndrome
(n = 12).Conclusion(s) These data indicate that survivin is expressed
in human germ cells and might be involved in apoptosis control during
spermatogenesis. Decreased survivin expression in spermatogenic disorders
may contribute to the accelerated germ cell apoptosis observed in
male idiopathic infertility.},
issn = {0015-0282},
keywords = {Apoptosis, male infertility, spermatogenesis, survivin, testicular
biopsy},
url = {http://www.sciencedirect.com/science/article/B6T6K-4FXM4M1-5/2/e5c0fb6dacd4ea08ad6ba2e8240a16a1}
}
@ARTICLE{Weil2004,
author = {Weil, M. Ryan and Widlak, Piotr and Minna, John D. and Garner, Harold
R.},
title = {Global Survey of Chromatin Accessibility Using DNA Microarrays},
journal = {Genome Res.},
year = {2004},
volume = {14},
pages = {1374--1381},
number = {7},
month = jul,
abstract = {An increasing number of studies indicate a central role for chromatin
remodeling in the regulation of gene expression. Current methods
for high-resolution studies of the relationship between chromatin
accessibility and transcription are low throughput, making a genome-wide
study impractical. To enable the simultaneous measurement of the
global chromatin accessibility state at the resolution of single
genes, we developed the Chromatin Array technique, in which chromatin
is separated by its condensation state using either the solubility
differences of mono- and oligonucleosomes in specific buffers or
controlled DNase I digestion and selection of the large refractory
(condensed) DNA fragments. By probing with a comparative genomic
hybridization style microarray, we can determine the condensation
state of thousands of individual loci and correlate this with transcriptional
activity. Applying this technique to the breast tumor model cell
line, MCF7, we found that when the condensation is homogeneous in
the population of cells, expression is inversely proportional to
the level of accessibility and the two methods of accessibility-based
target selection correlate well. Using functional annotation and
comparative genomic hybridization data, we have begun to decipher
the possible biological implications of the relationship between
chromatin accessibility and expression.},
url = {http://genome.cshlp.org/cgi/content/abstract/14/7/1374}
}
@ARTICLE{Weiland2007,
author = {Weiland, C. and Ahr, H.J. and Vohr, H.W. and Ellinger-Ziegelbauer,
H.},
title = {Characterization of primary rat proximal tubular cells by gene expression
analysis},
journal = {Toxicology in Vitro},
year = {2007},
volume = {21},
pages = {466--491},
number = {3},
month = apr,
abstract = {The kidney plays a major role in excretory and reabsorptive processes.
The kidney cortex consists primarily of proximal tubular cells, which
are epithelial cells that are often involved in the induction and
progression of various kidney diseases. Therefore primary proximal
tubular cells are widely used as a renal cell model. To further characterize
this kidney in vitro model different time points in culture after
isolation of the cells were compared to the cortex in vivo using
gene expression analysis based on microarrays. This study revealed
that many metabolic pathways and some kidney-specific functions are
lacking in the in vitro model. Furthermore genes involved in RNA
and protein synthesis, intracellular transport, extracellular matrix
and cytoskeletal organization were upregulated in culture compared
to in vivo, indicating proliferation of the cells and differentiation
into a cell culture phenotype. The data represented here may help
to evaluate the in vivo relevance of results obtained with this in
vitro model.},
issn = {0887-2333},
keywords = {Primary proximal tubular cells, Microarray, Cell culture, Gene expression
analysis},
url = {http://www.sciencedirect.com/science/article/B6TCP-4M5F317-1/2/c4c2788ef9a7ab5dab7542f912b534fa}
}
@ARTICLE{Weile2007,
author = {Weile, Jan and Schmid, Rolf D. and Bachmann, Till T. and Susa, Milorad
and Knabbe, Cornelius},
title = {DNA microarray for genotyping multidrug-resistant Pseudomonas aeruginosa
clinical isolates},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2007},
volume = {59},
pages = {325--338},
number = {3},
month = nov,
abstract = {The management of infections with multidrug-resistant Pseudomonas
aeruginosa needs fast and reliable methods of antibiotic susceptibility
testing for a therapy improvement. For this purpose, we developed
a DNA microarray for genotyping antibiotic resistance and a few virulence
factors. The array covers mutations in the efflux regulators mexR,
nfxB, mexT, gyrase gyrA, and parC, as well as plasmid-encoded vim,
imp, oxa, aph, aac, and aad genes, and virulence-associated mucA
and exoU, exoT, and exoS genes, respectively. The whole procedure
can be performed in less than 5 h and consists of DNA isolation,
target gene amplification, fluorescence labeling, fragmentation,
and array hybridization. Concerning the genotype-phenotype comparison
in the test collection, the coverage of relevant resistance determinants
for antibiotics used in a calculated therapy of critical ill patients
was 87.8%.},
issn = {0732-8893},
keywords = {Pseudomonas aeruginosa, DNA microarray, Antibiotic resistance, Nosocomial
infections, Multidrug resistance},
url = {http://www.sciencedirect.com/science/article/B6T60-4PPNM8G-1/2/c7dd31c2bef96e5fed5d5adf7725bdc5}
}
@ARTICLE{Wein2010,
author = {Wein, Silvia and Behm, Norma and Petersen, Rasmus K. and Kristiansen,
Karsten and Wolffram, Siegfried},
title = {Quercetin enhances adiponectin secretion by a PPAR-[gamma] independent
mechanism},
journal = {European Journal of Pharmaceutical Sciences},
year = {2010},
volume = {41},
pages = {16--22},
number = {1},
month = sep,
abstract = {To study possible insulin sensitizing, anti-inflammatory and anti-oxidative
effects of the flavonol quercetin, rats were fed a high-fat diet
(19%, w/w) with (HFQ) or without (HF) 0.03% quercetin or a flavonoid-poor
low-fat (5%, w/w) maintenance diet (LF) over 4 weeks. Body weight
was measured weekly, and plasma concentrations of adiponectin, leptin,
insulin, glucose, triacylglycerols, total cholesterol, as well as
of markers of inflammation and oxidative stress were measured (12 h
fasted) at the end of the feeding period. Adiponectin and peroxisome-proliferator-activated-receptor
(PPAR)-[gamma] mRNA were measured in adipose tissue (WAT) by real-time
RT-PCR. PPAR-[gamma] transactivation was investigated by means of
a reporter gene assay. HF feeding resulted in elevated fasted plasma
glucose concentrations, while HFQ did not differ from LF feeding.
In the HFQ group plasma concentrations and WAT mRNA levels of adiponectin
were elevated compared with the HF group, however, PPAR-[gamma] mRNA
concentration in WAT was decreased (HFQ vs. HF). Compared to both
other groups quercetin feeding significantly reduced oxidative stress,
measured by plasma 8-iso-PGF2[alpha], while body weight gain, body
composition and plasma leptin levels were not affected. Neither quercetin
nor its metabolites induced PPAR-[gamma]-mediated transactivation
in vitro. Adiponectin stimulating effects of quercetin are PPAR-[gamma]-independent
and prevent impairment of insulin sensitivity without affecting body
weight and composition.},
issn = {0928-0987},
keywords = {Flavonoids, Adiponectin, Peroxisome-proliferator-activated-receptor,
Oxidative stress, Quercetin},
url = {http://www.sciencedirect.com/science/article/B6T25-50393PF-3/2/aed4332d5146e288835305f3937fdb08}
}
@ARTICLE{Weiner2006,
author = {Weiner, Carl P. and Mason, Clifford and Hall, Gentzon and Ahmad,
Usma and Swaan, Peter and Buhimschi, Irina A.},
title = {Pregnancy and estradiol modulate myometrial G-protein pathways in
the guinea pig},
journal = {American Journal of Obstetrics and Gynecology},
year = {2006},
volume = {195},
pages = {275--287},
number = {1},
month = jul,
abstract = {Objective Coupled to hundreds of receptors, G-proteins modulate signal
transduction pathways and are important hormonal targets. The first
objective was to determine the effect of pregnancy and estradiol
on myometrial guanosine triphosphatase activity. The second objective
was to begin dissecting the molecular mechanism(s) underlying alterations
in guanosine triphosphatase activity.Study design Myometrial tissue
was obtained from pregnant, nonpregnant, and ovariectomized untreated
and estradiol-treated guinea pigs. Myometrial membranes were prepared
by homogenization and differential centrifugation. Basal high-affinity
specific guanosine triphosphatase activity was quantitated by enzymatic
assay and expressed in [rho]mol 32Pi per milligram protein per minute.
Guanosine triphosphatase activity was stimulated using oxytocin,
isoproterenol, and prostaglandin F2[alpha]. Specific G-protein subunits
were quantitated using Western blots. G-protein associated gene expression
was semiquantitated using HGU133A gene array chips from Affymetrix.Results
Basal myometrial guanosine triphosphatase activity was increased
in pregnant compared with nonpregnant animals. Estradiol increased
basal myometrial guanosine triphosphatase activity, compared with
untreated controls. The effect of estradiol on stimulated activity
was agonist dependent. Both G[alpha]s and G[alpha]i isoform 1 protein
levels were increased in myometrium from late pregnant compared with
nonpregnant animals. By late gestation, the messenger ribonucleic
acid levels of those genes were unaltered, compared with the nonpregnant
animal. In general, the impact of pregnancy on G-protein family member
gene messenger ribonucleic acid expression was modest. Only the small
guanosine triphosphatase Rap1b demonstrated altered expression more
than 2-fold during either myometrial quiescence (midpregnancy) or
activation (term pregnancy) (up 3-fold during quiescence). Genomic
network analyses revealed that the expression of another small guanosine
triphosphatase, Rab7, was exclusively up-regulated (80%) during quiescence.
During late pregnancy, network analysis showed that only G-protein
[beta] was exclusively altered (up-regulated). Estradiol mimicked
the pregnancy effect on both transcription and translation of G-protein
family members for some but not all potentially relevant genes.Conclusion
The increase in functional myometrial guanosine triphosphatase activity
during pregnancy may reflect increased synthesis of 1 or more small
guanosine triphosphatase.},
issn = {0002-9378},
keywords = {G-proteins, GTPase, Uterus, Myometrium, Quiescence, Oxytocin},
url = {http://www.sciencedirect.com/science/article/B6W9P-4JX378J-2/2/631b0ba7ee2b0183659e45f6e0045cd9}
}
@ARTICLE{Weinglass2008,
author = {Weinglass, Adam B. and Kohler, Martin G. and Nketiah, Emmanuel O.
and Liu, Jessica and Schmalhofer, William and Thomas, Anu and Williams,
Brande and Beers, Lindsey and Smith, Lauren and Hafey, Mike and Bleasby,
Kelly and Leone, Joseph and Tang, Yui Sing and Braun, Matthew and
Ujjainwalla, Feroze and McCann, Margaret E. and Kaczorowski, Gregory
J. and Garcia, Maria L.},
title = {Madin-Darby Canine Kidney II Cells: A Pharmacologically Validated
System for NPC1L1-Mediated Cholesterol Uptake},
journal = {Mol. Pharmacol.},
year = {2008},
volume = {73},
pages = {1072--1084},
number = {4},
month = apr,
abstract = {Absorption of dietary cholesterol in the proximal region of the intestine
is mediated by Niemann-Pick C1-like protein (NPC1L1) and is sensitive
to the cholesterol absorption inhibitor ezetimibe (EZE). Although
a correlation exists between EZE binding to NPC1L1 in vitro and efficacy
in vivo, the precise nature of interaction(s) between NPC1L1, EZE,
and cholesterol remain unclear. Here, we analyze the direct relationship
between EZE analog binding to NPC1L1 and its influence on cholesterol
influx in a novel in vitro system. Using the EZE analog [3H]AS, an
assay that quantitatively measures the expression of NPC1L1 on the
cell surface has been developed. It is noteworthy that whereas two
cell lines (CaCo-2 and HepG2) commonly used for studying NPC1L1-dependent
processes express almost undetectable levels of NPC1L1 at the cell
surface, polarized Madin-Darby canine kidney (MDCKII) cells endogenously
express 4 x 105 [3H]AS sites/cell under basal conditions. Depleting
endogenous cholesterol with the HMG CoA reductase inhibitor lovastatin
leads to a 2-fold increase in the surface expression of NPC1L1, supporting
the contention that MDCKII cells respond to changes in cholesterol
homeostasis by up-regulating a pathway for cholesterol influx. However,
a significant increase in surface expression levels of NPC1L1 is
necessary to characterize a pharmacologically sensitive, EZE-dependent
pathway of cholesterol uptake in these cells. Remarkably, the affinity
of EZE analogs for binding to NPC1L1 is almost identical to the IC50
blocking cholesterol flux through NPC1L1 in MDCKII cells. From a
mechanistic standpoint, these observations support the contention
that EZE analogs and cholesterol share the same/overlapping binding
site(s) or are tightly coupled through allosteric interactions.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/73/4/1072}
}
@ARTICLE{Weir2008,
author = {Weir, Tiffany L. and Stull, Valerie J. and Badri, Dayakar and Trunck,
Lily A. and Schweizer, Herbert P. and Vivanco, Jorge},
title = {Global Gene Expression Profiles Suggest an Important Role for Nutrient
Acquisition in Early Pathogenesis in a Plant Model of Pseudomonas
aeruginosa Infection},
journal = {Appl. Envir. Microbiol.},
year = {2008},
volume = {74},
pages = {5784--5791},
number = {18},
month = sep,
abstract = {Although Pseudomonas aeruginosa is an opportunistic pathogen that
does not often naturally infect alternate hosts, such as plants,
the plant-P. aeruginosa model has become a widely recognized system
for identifying new virulence determinants and studying the pathogenesis
of the organism. Here, we examine how both host factors and P. aeruginosa
PAO1 gene expression are affected in planta after infiltration into
incompatible and compatible cultivars of tobacco (Nicotiana tabacum
L.). N. tabacum has a resistance gene (N) against tobacco mosaic
virus, and although resistance to PAO1 infection is correlated with
the presence of a dominant N gene, our data suggest that it is not
a factor in resistance against PAO1. We did observe that the resistant
tobacco cultivar had higher basal levels of salicylic acid and a
stronger salicylic acid response upon infiltration of PAO1. Salicylic
acid acts as a signal to activate defense responses in plants, limiting
the spread of the pathogen and preventing access to nutrients. It
has also been shown to have direct virulence-modulating effects on
P. aeruginosa. We also examined host effects on the pathogen by analyzing
global gene expression profiles of bacteria removed from the intracellular
fluid of the two plant hosts. We discovered that the availability
of micronutrients, particularly sulfate and phosphates, is important
for in planta pathogenesis and that the amounts of these nutrients
made available to the bacteria may in turn have an effect on virulence
gene expression. Indeed, there are several reports suggesting that
P. aeruginosa virulence is influenced in mammalian hosts by the availability
of micronutrients, such as iron and nitrogen, and by levels of O2.},
url = {http://aem.asm.org/cgi/content/abstract/74/18/5784}
}
@ARTICLE{Weis2007,
author = {Weis, S. and Llenos, I.C. and Dulay, J.R. and Elashoff, M. and Martínez-Murillo,
F. and Miller, C.L.},
title = {Quality control for microarray analysis of human brain samples: The
impact of postmortem factors, RNA characteristics, and histopathology},
journal = {Journal of Neuroscience Methods},
year = {2007},
volume = {165},
pages = {198--209},
number = {2},
month = sep,
abstract = {The quality of results from microarray studies depends on RNA quality,
which can be significantly influenced by postmortem factors. The
aim of this study was to determine which postmortem factors and/or
RNA electropherogram characteristics best correspond to microarray
output and can be used to prospectively screen RNA prior to microarray
analysis. Total RNA was extracted (N = 125) from gray and white matter
of postmortem frontal and occipital lobe tissue, acquired from normal
controls, and patients with schizophrenia, bipolar disorder or major
depression. Electropherograms were generated by the Agilent BioAnalyzer
2100, allowing calculation of the 28S/18S ratio, the 18S/baseline
peak ratio and the RNA Integrity Number (RIN). These values were
compared to post-hybridization image analysis of Affymetrix microarrays.
The postmortem variables correlated with some quality measures but
could not be used as effective screening tools. Logistic regression
demonstrated that all three electropherogram measures were predictive
for microarray quality, and that the RIN threshold predictive of
"good quality" (>35% present calls) was most consistent with that
of prior studies. The optimal RIN must be determined by the investigator's
specifications for false inclusion and false exclusion. In contrast
to RIN, the quality threshold for the 28S/18S ratio has proven unacceptably
variable, due to sensitivity to slight differences in protocol and/or
tissue source. In conclusion, the measures we found useful as screening
criteria do not replace the need to exclude samples after a microarray
analysis is performed, as an acceptable percent call rate and other
measures of microarray quality represent the desired endpoint.},
issn = {0165-0270},
keywords = {RNA, Brain pH, Quality control, Microarray, Postmortem human brain,
Histopathology},
url = {http://www.sciencedirect.com/science/article/B6T04-4NX8MMG-2/2/fc81976f33fe3f3c84770cdb62da2017}
}
@ARTICLE{Weiss2012,
author = {Weiss, Arthur and Zikherman, Julie and Doan, Kristin and Parameswaran,
Ramya and Raschke, William and Weiss, Arthur},
title = {PNAS Plus: Quantitative differences in CD45 expression unmask functions
for CD45 in B-cell development, tolerance, and survival},
journal = {PNAS},
year = {2012},
volume = {109},
pages = {E3-12},
number = {1},
abstract = {The receptor-like tyrosine phosphatase CD45 positively regulates antigen
receptor signaling by dephosphorylating the inhibitory tyrosine of
the src family kinases. CD45-deficient mice fail to fully unmask
the role of CD45 in B cells because of the expression of a partially
redundant tyrosine phosphatase, CD148. However, mice that are doubly
deficient in CD45 and CD148 exhibit a very early block in B-cell
development, thereby obscuring later roles for CD45. To overcome
these limitations, here we take advantage of an allelic series of
mice in which CD45 expression is titrated broadly (0-180%). Although
high expression of CD45 inhibits T-cell receptor (TCR) signaling,
we show that CD45 plays a purely positive regulatory role during
B-cell receptor (BCR) signaling. In concert with exaggerated BCR
signaling, increasing CD45 expression drives enhanced receptor editing
in the bone marrow and profound loss of follicular and marginal zone
B cells in the spleen. In the context of the IgHEL/sHEL model of
B-cell tolerance, such high CD45 expression transforms anergy into
deletion. Unexpectedly, elimination of the autoantigen sHEL in this
model system in order to block clonal deletion fails to rescue survival
of mature B cells. Rather, high CD45 expression reduces B-cell activating
factor receptor (BAFFR) expression and inhibits B-cell activating
factor (BAFF)-induced B-cell survival in a cell-intrinsic manner.
Taken together, our findings reveal how CD45 function diverges in
T cells and B cells, as well as how autoreactive B cells are censored
as they transit development.},
doi = {10.1073/pnas.1117374108},
eprint = {http://www.pnas.org/cgi/reprint/109/1/E3.pdf},
url = {http://www.pnas.org/cgi/content/abstract/109/1/E3}
}
@ARTICLE{Weiss2011,
author = {Gudrun Weiss and Hanne Risager Christensen and Louise Hjerrild Zeuthen
and Finn Kvist Vogensen and Mogens Jakobsen and Hanne Frøkiær},
title = {Lactobacilli and bifidobacteria induce differential interferon-β
profiles in dendritic cells},
journal = {Cytokine},
year = {2011},
volume = {56},
pages = {520 - 530},
number = {2},
abstract = {The health promoting effects of probiotics are well-documented; however,
current knowledge on immunostimulatory effects is based on data from
a single strain or a limited selection of strains or species. Here,
we compared the capacity of 27 lactobacilli and 16 bifidobacteria
strains to stimulate bone marrow-derived dendritic cells (DC). Most
lactobacilli strains, including Lactobacillus acidophilus, Lactobacillus
gasseri, Lactobacillus casei and Lactobacillus plantarum, induced
strong IL-12 and TNF-α production and up-regulation of maturation
markers. In contrast, all bifidobacteria and certain lactobacilli
strains were low IL-12 and TNF-α inducers. IL-10 and IL-6 levels
showed less variation and no correlation with IL-12 and TNF-α.
DC matured by strong IL-12-inducing strains also produced high levels
of interferon (IFN)-β. When combining two strains, low IL-12 inducers
inhibited this IFN-β production as well as IL-12 and Th1-skewing
chemokines. The IFN-β induction was mediated through c-Jun N-terminal
kinase (JNK) irrespective of the stimulating strain. The inhibitory
bacteria induced higher levels of the transcription factor c-Jun
dimerization protein (JDP)-2, thereby counteracting the effect of
JNK. Our data demonstrate that lactobacilli can be divided into two
groups of bacteria featuring contrasting effects, while all bifidobacteria
exhibit uniform effects. This underlines the importance of selecting
the proper strain(s) for probiotic purposes.},
doi = {10.1016/j.cyto.2011.07.024},
issn = {1043-4666},
keywords = {Bifidobacteria},
url = {http://www.sciencedirect.com/science/article/pii/S1043466611002572}
}
@ARTICLE{Weiss2010,
author = {Weiss, Gudrun and Rasmussen, Simon and Zeuthen, Louise Hjerrild and
Nielsen, Birgit Nøhr and Jarmer, Hanne and Jespersen, Lene and Frøkiær,
Hanne},
title = {ORIGINAL ARTICLE: Lactobacillus acidophilus induces virus immune
defence genes in murine dendritic cells by a Toll-like receptor-2-dependent
mechanism},
journal = {Immunology},
year = {2010},
volume = {131},
pages = {268--281},
number = {2},
abstract = {Summary Lactobacilli are probiotics that, among other health-promoting
effects, have been ascribed immunostimulating and virus-preventive
properties. Certain Lactobacillus spp. have been shown to possess
strong interleukin-12 (IL-12) -inducing properties. As IL-12 production
depends on the up-regulation of type I interferons (IFNs), we hypothesized
that the strong IL-12-inducing capacity of Lactobacillus acidophilus
NCFM in murine bone-marrow-derived dendritic cells (DCs) is caused
by an up-regulation of IFN-β, which subsequently induces IL-12 and
the double-stranded RNA binding Toll-like receptor-3 (TLR-3). The
expression of the genes encoding IFN-β, TLR-3, IL-12 and IL-10 in
DCs upon stimulation with L. acidophilus NCFM was determined. Lactobacillus acidophilus
NCFM induced a much stronger expression of Ifn-β, Il-12 and Il-10
compared with the synthetic double-stranded RNA ligand Poly I:C,
whereas the levels of expressed Tlr-3 were similar. Whole genome
microarray gene expression analysis revealed that other genes related
to viral defence were significantly up-regulated and among the strongest
induced genes in DCs stimulated with L. acidophilus NCFM. The ability
to induce IFN-β was also detected in another L. acidophilus strain
(X37), but was not a property of other probiotic strains tested,
i.e. Bifidobacterium bifidum Z9 and Escherichia coli Nissle 1917.
The IFN-β expression was markedly reduced in TLR-2−/− DCs, dependent
on endocytosis, and the major cause of the induction of Il-12 and
Tlr-3 in DCs stimulated with L. acidophilus NCFM. Collectively,
our results reveal that certain lactobacilli trigger the expression
of viral defence genes in DCs in a TLR-2 manner dependent on IFN-β.},
issn = {1365-2567},
keywords = {dendritic cells, gene regulation, innate immune response, Lactobacillus
acidophilus, Toll-like receptor-2, virus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2010.03301.x}
}
@ARTICLE{Weiss2009,
author = {Weiss, Victor U. and Bilek, Gerhard and Pickl-Herk, Angela and Blaas,
Dieter and Kenndler, Ernst},
title = {Mimicking virus attachment to host cells employing liposomes: Analysis
by chip electrophoresis},
journal = {ELECTROPHORESIS},
year = {2009},
volume = {30},
pages = {2123--2128},
number = {12},
abstract = {Abstract 10.1002/elps.200900108.abs Electrophoresis on a chip increasingly
replaces electrophoresis in the capillary format because of its speed
and containment of the sample within a disposable cartridge. In this
paper we demonstrate its utility in the analysis of the interaction
between a virus and a liposome-anchored receptor, mimicking viral
attachment to host cells. This became possible because detergents,
obligatory constituents of the BGE for capillary electrophoretic
separation of the virus, were not necessary in the chip format. Separations
were carried out in sodium borate buffer, pH 8.3. Liposomes and virus
were both labeled for laser-induced fluorescence detection at λex/λem
630/680 nm. Free virus and virus-receptor complexes were resolved
from virus attached to receptor-decorated liposomes in the absence
of additives or sieving matrices within about 30 s on commercially
available microfluidic chips.},
issn = {1522-2683},
keywords = {Chip electrophoresis, Fluorescence labeling, Human rhinovirus, Liposome,
Very-low-density lipoprotein receptor},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200900108}
}
@ARTICLE{Weiss2010a,
author = {Weiss, Victor U. and Bilek, Gerhard and Pickl-Herk, Angela and Subirats,
Xavier and Niespodziana, Katarzyna and Valenta, Rudolf and Blaas,
Dieter and Kenndler, Ernst},
title = {Liposomal Leakage Induced by Virus-Derived Peptides, Viral Proteins,
and Entire Virions: Rapid Analysis by Chip Electrophoresis},
journal = {Analytical Chemistry},
year = {2010},
volume = {82},
pages = {8146-8152},
number = {19},
doi = {10.1021/ac101435v},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac101435v},
url = {http://pubs.acs.org/doi/abs/10.1021/ac101435v}
}
@ARTICLE{Weiss2007,
author = {Weiss, Victor U. and Kolivoska, Viliam and Kremser, Leopold and Gas,
Bohuslav and Blaas, Dieter and Kenndler, Ernst},
title = {Virus analysis by electrophoresis on a microfluidic chip},
journal = {Journal of Chromatography B},
year = {2007},
volume = {860},
pages = {173--179},
number = {2},
month = dec,
abstract = {Exploiting the advantages of miniaturization of analytical devices
we worked out conditions for the analysis of viruses, subviral particles,
and virus-receptor complexes on microfluidic chips. To allow for
detection via laser-induced fluorescence, the viral capsids were
labelled with the fluorescent dye Cy5. We analyzed human rhinovirus
serotype 2 and subviral particles, followed the complexation of the
virus with a synthetic fragment of the VLDL-receptor, and tracked
the heat-induced conversion of intact virions into empty capsids.
In contrast to fused silica capillaries, the glass micro-channels
allowed for electrophoresis of the analytes without detergent, and
analyses were accomplished within few tens of seconds. This opens
the avenue towards the analytics of membrane-enveloped viruses and
other biological assemblies that are not stable in the presence of
detergent. The chip format has the additional advantage of containment
and easy disposal, making it particularly attractive for the analysis
of infectious material.},
issn = {1570-0232},
keywords = {Chip electrophoresis, Fluorescence, Virus, Cy5, HRV2, VLDL-receptor,
Concatemer, Lab-on-a-chip},
url = {http://www.sciencedirect.com/science/article/B6X0P-4R0KT6K-3/2/1623d88cbad7e371194b421497c0f435}
}
@ARTICLE{Weix2012,
author = {Weix, Janine and Förger, Frauke and Häupl, Thomas and Surbek, Daniel
and Østensen, Monika and Villiger, Peter M.},
title = {Influence of pregnancy on the adipocytokine and PPAR pathways in
peripheral blood mononuclear cells of healthy donors and RA patients},
journal = {Arthritis \& Rheumatism},
year = {2012},
pages = {n/a--n/a},
abstract = {Objective:To identify candidate genes which are regulated by human
pregnancy and bear the potential to modulate rheumatoid arthritis
(RA) disease activity.Methods:Peripheral blood mononuclear cells
(PBMC) of healthy volunteers (ND) were analyzed using Affymetrix
GeneChips at four time points (1st, 2nd and 3rd trimester and 6 weeks
postpartum). Based on the GeneChip data, target genes were further
analyzed via quantitative real-time PCR (qPCR) using PBMC from ND
and RA patients. In order to determine the cellular source, monocytes
and lymphocytes from ND and RA patients were positively selected
using magnetic beads and their mRNA was analyzed by qPCR.Results:One-way
ANOVA analysis identified 1286 mRNAs differentially expressed with
regard to the four time points. The changes became more pronounced
as pregnancy progressed and they were reverted postpartum. A subsequent
pathway analysis suggested a regulatory role of pregnancy on the
adipocytokine pathway as well as the PPAR-signaling pathway. Of 19
pre-selected candidate genes, AKT3, SOCS3, FADS2, STAT1 and CD36
proofed to be differentially regulated by pregnancy. In samples of
RA patients the differences were concordant but more pronounced.
Both, T lymphocytes and monocytes contributed to the regulated expression
of these genes.Conclusions:Normal human pregnancy leads to changes
in the expression level of several molecular pathways in PBMC which
are reverted postpartum. Changes in RA, though concordant, exceed
levels observed in ND. Genes of the adipocytokine- and the PPAR-signaling
pathways qualify as candidates for the modulation of RA disease activity
during pregnancy.},
doi = {10.1002/art.34375},
issn = {1529-0131},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/art.34375}
}
@ARTICLE{Welle2009,
author = {Welle, Stephen and Burgess, Kerri and Mehta, Sangeeta},
title = {Stimulation of skeletal muscle myofibrillar protein synthesis, p70
S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation
by inhibition of myostatin in mature mice},
journal = {Am J Physiol Endocrinol Metab},
year = {2009},
volume = {296},
pages = {E567--572},
number = {3},
month = mar,
abstract = {Knocking out myostatin activity during development increases the rate
of muscle protein synthesis. The present study was done to determine
whether postdevelopmental loss of myostatin activity stimulates myofibrillar
protein synthesis and the phosphorylation of some of the proteins
involved in regulation of protein synthesis rate. Myostatin activity
was inhibited for 4 days, in 4- to 5-mo-old male mice, with injections
of an anti-myostatin antibody (JA16). The mean myofibrillar synthesis
rate increased 19% (P < 0.01) relative to the mean rate in saline-treated
mice, as determined by incorporation of deuterium-labeled phenylalanine.
JA16 increased phosphorylation of p70 S6 kinase (S6K) and ribosomal
protein S6 (rpS6) 1.9-fold (P < 0.05). It did not affect phosphorylation
of eukaryotic initiation factor 4E-binding protein-1 or Akt. Microarrays
and real-time PCR analyses indicated that JA16 administration did
not selectively enrich levels of mRNAs encoding myofibrillar proteins,
ribosomal proteins, or translation initiation and elongation factors.
Rapamycin treatment did not affect the rate of myofibrillar protein
synthesis whether or not the mice received JA16 injections, although
it eliminated the phosphorylation of S6K and rpS6. We conclude that
the normal level of myostatin activity in mature muscle is sufficient
to inhibit myofibrillar synthesis rate and phosphorylation of S6K
and rpS6. Reversal of the inhibition of myofibrillar synthesis with
an anti-myostatin antibody is not dependent on mTOR activation.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/296/3/E567}
}
@ARTICLE{Welle2009a,
author = {Welle, Stephen and Burgess, Kerri and Thornton, Charles A. and Tawil,
Rabi},
title = {Relation between extent of myostatin depletion and muscle growth
in mature mice},
journal = {Am J Physiol Endocrinol Metab},
year = {2009},
volume = {297},
pages = {E935--940},
number = {4},
month = oct,
abstract = {Myostatin is a negative regulator of muscle growth and fiber size.
Changes in myostatin expression might contribute to changes in muscle
mass associated with various conditions, and reducing the amount
of active myostatin is a potential strategy for preventing or reversing
muscle atrophy. The present study was done to determine the extent
to which myostatin levels must decline to induce growth of mature
muscles. Myostatin expression was reduced by activating Cre recombinase
in adult mice with floxed myostatin genes. The duration of Cre activation
varied from 1 to 6 wk, and the residual myostatin mRNA expression
after Cre activation varied from 3 to 63% of the normal level. Promyostatin
levels declined in parallel with myostatin mRNA. There was no increase
in muscle mass over the 3 mo following Cre activation if residual
myostatin expression was [≥]40% of normal. In mice with <40% of
normal myostatin expression, muscle mass increased in proportion
to the extent of myostatin depletion. In mice with [≤]10% of normal
myostatin expression, muscle mass increased [~]25%. Myostatin depletion
increased myonuclear domain volumes and the ratio of RNA to myonuclei
probably by enhancing DNA transcription rather than by inhibiting
RNA decay. There was no evidence that maintenance of the hypertrophy
during chronic myostatin deficiency requires altered activity of
Akt/mTOR or p38 MAPK signaling pathways. These data suggest that
anabolic therapies based on reducing the concentration of active
myostatin will be effective only if a very large proportion of the
myostatin is removed or inactivated.},
url = {http://ajpendo.physiology.org/cgi/content/abstract/297/4/E935}
}
@ARTICLE{Welle2009b,
author = {Welle, Stephen and Cardillo, Andrew and Zanche, Michelle and Tawil,
Rabi},
title = {Skeletal muscle gene expression after myostatin knockout in mature
mice},
journal = {Physiol Genomics},
year = {2009},
volume = {38},
pages = {342--350},
number = {3},
month = aug,
abstract = {There is much interest in developing anti-myostatin agents to reverse
or prevent muscle atrophy in adults, so it is important to characterize
the effects of reducing myostatin activity after normal muscle development.
For assessment of the effect of loss of myostatin signaling on gene
expression in muscle, RNA from mice with postdevelopmental myostatin
knockout was analyzed with oligonucleotide microarrays. Myostatin
was undetectable in muscle within 2 wk after Cre recombinase activation
in 4-month-old male mice with floxed myostatin genes. Three months
after myostatin depletion, muscle mass had increased 26% (vs. 2%
after induction of Cre activity in mice with normal myostatin genes),
at which time the expression of several hundred genes differed in
knockout and control mice at nominal P < 0.01. In contrast to previously
reported effects of constitutive myostatin knockout, postdevelopmental
knockout did not downregulate expression of genes encoding slow isoforms
of contractile proteins or genes encoding proteins involved in energy
metabolism. Several collagen genes were expressed at 20-50% lower
levels in the myostatin-deficient muscles, which had [~]25% less
collagen than normal muscles as reflected by hydroxyproline content.
Most of the other genes affected by myostatin depletion have not
been previously linked to myostatin signaling. Gene set enrichment
analysis suggested that Smads are not the only transcription factors
with reduced activity after myostatin depletion. These data reinforce
other evidence that myostatin regulates collagen production in muscle
and demonstrate that many of the previously reported effects of constitutive
myostatin deficiency do not occur when myostatin is knocked out in
mature muscles.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/38/3/342}
}
@ARTICLE{WellehanJr.2009,
author = {Wellehan Jr., James F.X. and Green, Linda G. and Duke, Diane G. and
Bootorabi, Shadi and Heard, Darryl J. and Klein, Paul A. and Jacobson,
Elliott R.},
title = {Detection of specific antibody responses to vaccination in variable
flying foxes (Pteropus hypomelanus)},
journal = {Comparative Immunology, Microbiology and Infectious Diseases},
year = {2009},
volume = {32},
pages = {379--394},
number = {5},
month = sep,
abstract = {Megachiropteran bats are biologically important both as endangered
species and reservoirs for emerging human pathogens. Reliable detection
of antibodies to specific pathogens in bats is thus epidemiologically
critical. Eight variable flying foxes (Pteropus hypomelanus) were
immunized with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA).
Each bat received monthly inoculations for 2 months. Affinity-purified
IgG was used for production of polyclonal and monoclonal anti-variable
flying fox IgG antibodies. ELISA and western blot analysis were used
to monitor immune responses and for assessment of polyclonal and
monoclonal antibody species cross-reactivity. Protein G, polyclonal
antibodies, and monoclonal antibodies detected specific anti-DNP
antibody responses in immunized variable flying foxes, with protein
G being the most sensitive, followed by monoclonal antibodies and
then polyclonal antibodies. While the polyclonal antibody was found
to cross-react well against IgG of all bat species tested, some non-specific
background was observed. The monoclonal antibody was found to cross-react
well against IgG of six other species in the genus Pteropus and to
cross-react less strongly against IgG from Eidolon helvum or Phyllostomus
hastatus. Protein G distinguished best between vaccinated and unvaccinated
bats, and these results validate the use of protein G for detection
of bat IgG. Monoclonal antibodies developed in this study recognized
immunoglobulins from other members of the genus Pteropus well, and
may be useful in applications where specific detection of Pteropus
IgG is needed.},
issn = {0147-9571},
keywords = {Bats, Flying fox, Pteropus hypomelanus, Antibody, Protein G, ELISA,
Chauves-souris, Roussette, Pteropus hypomelanus, Anticorps, Protéine
G, ELISA},
url = {http://www.sciencedirect.com/science/article/B6T5H-4RR831X-2/2/706232b10cd56a9ff9e445f07e7daa9b}
}
@ARTICLE{Wellensiek2009,
author = {Wellensiek, Brian P. and Ramakrishnan, Rajesh and Sundaravaradan,
Vasudha and Mehta, Roshni and Harris, David T. and Ahmad, Nafees},
title = {Differential HIV-1 integration targets more actively transcribed
host genes in neonatal than adult blood mononuclear cells},
journal = {Virology},
year = {2009},
volume = {385},
pages = {28--38},
number = {1},
month = mar,
abstract = {We have recently shown an increased HIV-1 replication and gene expression
in neonatal (cord) blood mononuclear cells compared with adult cells,
which could be due to HIV-1 integration as it targets active host
genes. Here we have characterized 468 HIV-1 integration sites within
cord and adult blood T-lymphocytes and monocyte-derived macrophages
(MDM) from five donors. Several functional classes of genes were
identified by gene ontology to be over represented, including genes
for cellular components, maintenance of intracellular environment,
enzyme regulation, cellular metabolism, catalytic activity and cation
transport. Numerous potential transcription factor binding sites
at the sites of integration were identified. Furthermore, the genes
at the site of integration, transcription factors which potentially
bind upstream of the HIV-1 promoter and factors that assist HIV-1
integration were found to be expressed at higher levels in cord than
adult cells. Taken together, these results suggest HIV-1 integration
occurred in a more actively transcribed genes in neonatal cells compared
with adult cells, which may help explain a higher level of HIV-1
gene expression and replication in neonatal compared with adult cells.},
issn = {0042-6822},
keywords = {HIV-1, Integration, Gene expression, Neonatal cells, Cord blood cells},
url = {http://www.sciencedirect.com/science/article/B6WXR-4V5NSTR-1/2/50ca554d18087555c0c442374d9babbd}
}
@ARTICLE{Wellmann2004,
author = {Wellmann, Sven and Buhrer, Christoph and Moderegger, Eva and Zelmer,
Andrea and Kirschner, Renate and Koehne, Petra and Fujita, Jun and
Seeger, Karl},
title = {Oxygen-regulated expression of the RNA-binding proteins RBM3 and
CIRP by a HIF-1-independent mechanism},
journal = {J. Cell Sci.},
year = {2004},
volume = {117},
pages = {1785--1794},
number = {9},
month = may,
abstract = {The transcriptional regulation of several dozen genes in response
to low oxygen tension is mediated by hypoxia-inducible factor 1 (HIF-1),
a heterodimeric protein composed of two subunits, HIF-1{alpha} and
HIF-1{beta}. In the HIF-1{alpha}-deficient human leukemic cell line,
Z-33, exposed to mild (8% O2) or severe (1% O2) hypoxia, we found
significant upregulation of two related heterogenous nuclear ribonucleoproteins,
RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding
protein (CIRP), which are highly conserved cold stress proteins with
RNA-binding properties. Hypoxia also induced upregulation of RBM3
and CIRP in the murine HIF-1{beta}-deficient cell line, Hepa-1 c4.
In various HIF-1 competent cells, RBM3 and CIRP were induced by moderate
hypothermia (32{degrees}C) but hypothermia was ineffective in increasing
HIF-1{alpha} or vascular endothelial growth factor (VEGF), a known
HIF-1 target. In contrast, iron chelators induced VEGF but not RBM3
or CIRP. The RBM3 and CIRP mRNA increase after hypoxia was inhibited
by actinomycin-D, and in vitro nuclear run-on assays demonstrated
specific increases in RBM3 and CIRP mRNA after hypoxia, which suggests
that regulation takes place at the level of gene transcription. Hypoxia-induced
RBM3 or CIRP transcription was inhibited by the respiratory chain
inhibitors NaN3 and cyanide in a dose-dependent fashion. However,
cells depleted of mitochondria were still able to upregulate RBM3
and CIRP in response to hypoxia. Thus, RBM3 and CIRP are adaptatively
expressed in response to hypoxia by a mechanism that involves neither
HIF-1 nor mitochondria.},
url = {http://jcs.biologists.org/cgi/content/abstract/117/9/1785}
}
@ARTICLE{Wells2008,
author = {Wells, Christine A. and Salvage-Jones, Judith A. and Li, Xin and
Hitchens, Kelly and Butcher, Suzanne and Murray, Rachael Z. and Beckhouse,
Anthony G. and Lo, Yu-Lan-Sandra and Manzanero, Silvia and Cobbold,
Christian and Schroder, Kate and Ma, Bo and Orr, Sally and Stewart,
Lauren and Lebus, Daniel and Sobieszczuk, Peter and Hume, David A.
and Stow, Jennifer and Blanchard, Helen and Ashman, Robert B.},
title = {The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component
of the Innate Immune Response to Candida albicans},
journal = {J. Immunol.},
year = {2008},
volume = {180},
pages = {7404--7413},
number = {11},
month = jun,
abstract = {The recognition of carbohydrate moieties by cells of the innate immune
system is emerging as an essential element in antifungal immunity,
but despite the number and diversity of lectins expressed by innate
immune cells, few carbohydrate receptors have been characterized.
Mincle, a C-type lectin, is expressed predominantly on macrophages,
and is here shown to play a role in macrophage responses to the yeast
Candida albicans. After exposure to the yeast in vitro, Mincle localized
to the phagocytic cup, but it was not essential for phagocytosis.
In the absence of Mincle, production of TNF-{alpha} by macrophages
was reduced, both in vivo and in vitro. In addition, mice lacking
Mincle showed a significantly increased susceptibility to systemic
candidiasis. Thus, Mincle plays a novel and nonredundant role in
the induction of inflammatory signaling in response to C. albicans
infection.},
url = {http://www.jimmunol.org/cgi/content/abstract/180/11/7404}
}
@ARTICLE{Wells2008a,
author = {Wells, Dagan and Patrizio, Pasquale},
title = {Gene expression profiling of human oocytes at different maturational
stages and after in vitro maturation},
journal = {American Journal of Obstetrics and Gynecology},
year = {2008},
volume = {198},
pages = {455.e1--455.e11},
number = {4},
month = apr,
abstract = {Objective The purpose of this study was to catalog genes expressed
in human oocytes at germinal vesicle (GV) or metaphase II (MII) stage
and to compare gene profiles between oocytes matured in vivo (in
vivo-MII) and in vitro (IVM-MII).Study Design University-based research
utilizing unfertilized oocytes analyzed for > 29,000 genes with RNA
amplification and microarray.Results GV, in vivo-MII, and IVM-MII
oocytes expressed 12,219, 9735, and 8510 genes, respectively. There
was extensive overlap among the 3 groups, but also some significant
differences. In particular, in vivo-MII and IVM-MII oocytes shared
very similar patterns of gene expression. However, some immature
patterns of expression, reminiscent of GVs, persisted in IVM-MIIs.Conclusion
In vitro maturation is an attractive strategy for IVF treatment;
however, current IVM methods produce oocytes that perform poorly
in the context of IVF. Data from the current study suggest that although
IVM-MII oocytes closely resemble in vivo-MII oocytes for cellular
pathways related to nuclear maturity, several pathways associated
with cytoplasmic functions continue to be expressed in an immature
manner. Additionally, IVM-MII oocytes have differences in the expression
of genes related to cellular storage and homeostasis. Differentially
expressed genes/pathways provide clues for the optimization of IVM
techniques.},
issn = {0002-9378},
keywords = {gene expression, germinal vesicle, in vitro maturation, microarray,
oocyte},
url = {http://www.sciencedirect.com/science/article/B6W9P-4S6GBHH-D/2/e3a116f34680a90f2325b5f15aacd77d}
}
@ARTICLE{Welsch2004,
author = {Welsch, Carole A. and Roth, Lukas W. A. and Goetschy, Jean Francois
and Movva, N. Rao},
title = {Genetic, Biochemical, and Transcriptional Responses of Saccharomyces
cerevisiae to the Novel Immunomodulator FTY720 Largely Mimic Those
of the Natural Sphingolipid Phytosphingosine},
journal = {J. Biol. Chem.},
year = {2004},
volume = {279},
pages = {36720--36731},
number = {35},
month = aug,
abstract = {Sphingolipids are signaling molecules that influence diverse cellular
functions from control of the cell cycle to degradation of plasma
membrane proteins. The synthetic sphingolipid-like compound FTY720
is an immunomodulating agent in clinical trials for transplant graft
maintenance. In this report, we compare the effects of the natural
yeast sphingolipid phytosphingosine with FTY720 in Saccharomyces
cerevisiae. We show that the multicopy suppressor genes that induce
growth resistance to FTY720 also confer resistance to growth-inhibitory
concentrations of phytosphingosine. In addition, mutants for ubiquitination
pathway proteins are shown to be resistant to the growth-inhibiting
effect of both FTY720 and phytosphingosine. We observe fewer similarities
between sphingosine and FTY720 than between FTY720 and phytosphingosine
as revealed by genetic studies. Yeast cells lacking the specific
sphingosine kinase LCB4 are sensitive to phytosphingosine and FTY720
but resistant to sphingosine, suggesting that FTY720 and phytosphingosine
have a more related mechanism of action. Gene expression profile
comparisons of sensitive and resistant yeast cells exposed to FTY720
and phytosphingosine highlight a number of similarities. In response
to treatment with these compounds, [~]77% of the genes that are regulated
>2-fold by FTY720 also respond to phytosphingosine in the same direction
in the parent strain. In addition, a close inspection of TAT1 and
TAT2 transporters following exposure to phytosphingosine indicates
that TAT1 protein is degraded in a similar fashion upon treatment
with FTY720 and phytosphingosine. There were differences, however,
with respect to the TAT2 protein level and the expression profiles
of a subset of genes. The genetic, transcriptional, and biochemical
data together indicate that FTY720 and phytosphingosine influence
similar pathways in yeast cells. These findings offer further insights
into the physiological pathways influenced by these compounds in
all eukaryotic cells and help us to understand the therapeutic consequences
of FTY720 in humans.},
url = {http://www.jbc.org/cgi/content/abstract/279/35/36720}
}
@ARTICLE{Welsh2007,
author = {Welsh, Ian C. and Hagge-Greenberg, Aaron and O'Brien, Timothy P.},
title = {A dosage-dependent role for Spry2 in growth and patterning during
palate development},
journal = {Mechanisms of Development},
year = {2007},
volume = {124},
pages = {746--761},
number = {9-10},
month = sep,
abstract = {The formation of the palate involves the coordinated outgrowth, elevation
and midline fusion of bilateral shelves leading to the separation
of the oral and nasal cavities. Reciprocal signaling between adjacent
fields of epithelial and mesenchymal cells directs palatal shelf
growth and morphogenesis. Loss of function mutations in genes encoding
FGF ligands and receptors have demonstrated a critical role for FGF
signaling in mediating these epithelial-mesenchymal interactions.
The Sprouty family of genes encode modulators of FGF signaling. We
have established that mice carrying a deletion that removes the FGF
signaling antagonist Spry2 have cleft palate. We show that excessive
cell proliferation in the Spry2-deficient palate is accompanied by
the abnormal progression of shape changes and movements required
for medially directed shelf outgrowth and midline contact. Expression
of the FGF responsive transcription factors Etv5, Msx1, and Barx1,
as well as the morphogen Shh, is restricted to specific regions of
the developing palate. We detected elevated and ectopic expression
of these transcription factors and disorganized Shh expression in
the Spry2-deficient palate. Mice carrying a targeted disruption of
Spry2 fail to complement the craniofacial phenotype characterized
in Spry2 deletion mice. Furthermore, a Spry2-BAC transgene rescues
the palate defect. However, the BAC transgenic mouse lines express
reduced levels of Spry2. The resulting hypomorphic phenotype demonstrates
that palate development is Spry2 dosage sensitive. Our results demonstrate
the importance of proper FGF signaling thresholds in regulation of
epithelial-mesenchymal interactions and cellular responses necessary
for coordinated morphogenesis of the face and palate.},
issn = {0925-4773},
keywords = {Cleft palate, Epithelial-mesenchymal interaction, FGF signaling, Spry2,
Craniofacial development, Patterning, Hypomorphic phenotype},
url = {http://www.sciencedirect.com/science/article/B6T9H-4P59X4J-1/2/eb0af300d20c51f8deea73b85024fc3d}
}
@ARTICLE{Welzel2011,
author = {Maik Welzel and Mahesh Appari and Nuria Bramswig and Felix G. Riepe
and Paul-Martin Holterhus},
title = {Transcriptional response of peripheral blood mononuclear cells to
recombinant human growth hormone in a routine four-days IGF-I generation
test},
journal = {Growth Hormone \& IGF Research},
year = {2011},
volume = {21},
pages = {336 - 342},
number = {6},
abstract = {Background There are very few laboratory markers which reflect the
biological sensitivity of children to recombinant human growth hormone
(rhGH) treatment. Genome-wide transcriptional changes in peripheral
blood mononuclear cells (PBMC) have been widely used as functional
readout for different pharmacological stimuli. Objective To characterize
transcriptional changes in PBMC induced by rhGH during a routine
short-term IGF-I generation test (IGFGT) in children with growth
disorders. Materials and methods Blood was obtained for IGF-I determination
and RNA-preparation from PBMC of 12 children before and after 4 days
treatment with 30 μg rhGH/kg body weight/day s.c. Transcriptional
changes were assessed by cDNA-microarrays in the first six children.
Selected genes were validated in all 12 cases by RT-qPCR. Results
Serum IGF-I rose in all patients except one (p < 0.0001),
confirming biological response to rhGH. Unsupervised microarray data
analysis in the first six children revealed 313 transcripts with
abundant transcriptional changes but considerable inter-individual
variability of response patterns. Many patients showed a large cluster
of up-regulated genes, including EGR1, EGR2, FOS and to a lesser
extent STAT2 and 5b. Exemplarily, EGR1, EGR2 and FOS data were independently
reproduced by RT-qPCR. Gene ontology analysis revealed that pathways
involved in cell proliferation and immune functions were significantly
over represented. Conclusion The IGFGT is a suitable method for measuring
reproducible and biologically conclusive transcriptional changes
in PBMC. As our unsupervised data analysis strategy exposed a considerable
inter-individual variability of response profiles a search for molecules
of diagnostic and even prognostic value needs to be based on large
long-term studies.},
doi = {10.1016/j.ghir.2011.09.001},
issn = {1096-6374},
keywords = {Growth hormone},
url = {http://www.sciencedirect.com/science/article/pii/S109663741100102X}
}
@ARTICLE{Wen2011,
author = {Wen, Jia and Deng, Xiangyu and Li, Zengxin and Dudley, Edward G.
and Anantheswaran, Ramaswamy C. and Knabel, Stephen J. and Zhang,
Wei},
title = {Transcriptomic Response of Listeria monocytogenes during the Transition
to the Long-Term-Survival Phase},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {5966-5972},
number = {17},
abstract = {Listeria monocytogenes can change its cellular morphology from bacilli
to cocci during the transition to the long-term-survival (LTS) phase.
The LTS cells demonstrated increased baro- and thermotolerance compared
to their vegetative counterparts. So far, the underlying mechanisms
that trigger this morphological and physiological transition remain
largely unknown. In this study, we compared the transcriptomic profiles
of L. monocytogenes serotype 4b strain F2365 at different growth
stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome
DNA chip approach. We identified a total of 225 differentially expressed
genes ([≥]4-fold; P < 0.05) during the transition to the LTS phase
in TSBYE. Genes related to cell envelope structure, energy metabolism,
and transport were most significantly upregulated in the LTS phase.
The upregulation of compatible solute transporters may lead to the
accumulation of cellular solutes, lowering intracellular water activity
and thus increasing bacterial stress resistance during the transition
to the LTS phase. The downregulation of genes associated with protein
synthesis may indicate a status of metabolic dormancy of the LTS
cells. The transcriptomic profiles of resuscitated LTS cells in fresh
TSBYE resembled those of log-phase cells (r=0.94), as the LTS cells
rapidly resume metabolic activities and transit back to log phase
with decreased baro- and thermotolerance.},
doi = {10.1128/AEM.00596-11},
eprint = {http://aem.asm.org/cgi/reprint/77/17/5966.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/17/5966}
}
@ARTICLE{Wen2011b,
author = {Quan Wen and Yide Hu and Xi Zhang and Peiyan Kong and Xinghua Chen},
title = {Gene expression signature of lymphocyte in acute lymphoblastic leukemia
patients immediately after total body irradiation},
journal = {Leukemia Research},
year = {2011},
volume = {35},
pages = {1044 - 1051},
number = {8},
abstract = {Molecular mechanisms involved in TBI preconditioning before allogenetic
transplantation remain unclear. To elucidate possible signaling pathway
in it, gene expression profiles of peripheral lymphocytes were compared
between samples 24 h after each 4.5 Gy total body irradiation
treatment (total 9 Gy) from 4 adult ALL patients. 478 significant
expressed genes and three unique patterns were identified. Of these,
a dominant progressively repressed expression of genes involved in
ubiquitin-dependent process and repressed expression only at 9 Gy
of genes involved in allograft rejection and graft-versus-host disease
pathways were observed. The results suggest these pathways may play
important roles for subsequent transplantation.},
doi = {10.1016/j.leukres.2010.12.026},
issn = {0145-2126},
keywords = {Acute lymphoblastic leukemia},
url = {http://www.sciencedirect.com/science/article/pii/S0145212610006259}
}
@ARTICLE{Wen2006,
author = {Wen, Weiyan and Sanelli, Teresa and Ge, Weiwen and Strong, Wendy
and Strong, Michael J.},
title = {Activated microglial supernatant induced motor neuron cytotoxicity
is associated with upregulation of the TNFR1 receptor},
journal = {Neuroscience Research},
year = {2006},
volume = {55},
pages = {87--95},
number = {1},
month = may,
abstract = {We have previously reported that supernatant derived from LPS-activated
BV-2 cells, an immortalized microglial cell line, induces death of
NSC-34 cells (a motor neuron hybridoma) through a TNF[alpha] and
nitric oxide synthase (NOS) dependant mechanism. In this study, we
have observed that LPS-activated BV-2 supernatant induces NSC-34
cell death in association with an upregulation of the TNF receptor
1 (TNFR1) expression on NSC-34 cells, both at the transcription level
and at the cell surface protein level. The upregulation of TNFR1
receptor was independent of TNF[alpha], and could be partly inhibited
by the inhibition of iNOS activation in the BV-2 cells. The TNFR2
receptor was not involved. These observations have important implications
in understanding the mechanism by which microglial activation contributes
to the motor neuron degeneration.},
issn = {0168-0102},
keywords = {Microglia, TNF[alpha], Motor neuron, Cytotoxicity, TNFR1, ALS},
url = {http://www.sciencedirect.com/science/article/B6T0H-4JFGF3C-2/2/20d1437fe1f59ba201bfb5d6214477a9}
}
@ARTICLE{Wen2011d,
author = {Wen, Yi and Feng, Jing and Scott, David R. and Marcus, Elizabeth
A. and Sachs, George},
title = {A cis-Encoded Antisense Small RNA Regulated by the HP0165-HP0166
Two-Component System Controls Expression of ureB in Helicobacter
pylori},
journal = {J. Bacteriol.},
year = {2011},
volume = {193},
pages = {40--51},
number = {1},
month = jan,
abstract = {Expression of urease is essential for gastric colonization by Helicobacter
pylori. The increased level of urease in gastric acidity is due,
in part, to acid activation of the two-component system (TCS) consisting
of the membrane sensor HP0165 and its response regulator, HP0166,
which regulates transcription of the seven genes of the urease gene
cluster. We now find that there are two major ureAB transcripts:
a 2.7-kb full-length ureAB transcript and a 1.4-kb truncated transcript
lacking 3' ureB. Acidic pH (pH 4.5) results in a significant increase
in transcription of ureAB, while neutral pH (pH 7.4) increases the
truncated 1.4-kb transcript. Northern blot analysis with sense RNA
and strand-specific oligonucleotide probes followed by 5' rapid amplification
of cDNA ends detects an antisense small RNA (sRNA) encoded by the
5' ureB noncoding strand consisting of [~]290 nucleotides (5'ureB-sRNA).
Deletion of HP0165 elevates the level of the truncated 1.4-kb transcript
along with that of the 5'ureB-sRNA at both pH 7.4 and pH 4.5. Overexpression
of 5'ureB-sRNA increases the 1.4-kb transcript, decreases the 2.7-kb
transcript, and decreases urease activity. Electrophoretic mobility
shift assay shows that unphosphorylated HP0166 binds specifically
to the 5'ureB-sRNA promoter. The ability of the HP0165-HP0166 TCS
to both increase and decrease ureB expression at low and high pHs,
respectively, facilitates gastric habitation and colonization over
the wide range of intragastric pHs experienced by the organism.},
comment = {10.1128/JB.00800-10},
url = {http://jb.asm.org/cgi/content/abstract/193/1/40}
}
@ARTICLE{Wen2009,
author = {Wen, Yi and Feng, Jing and Scott, David R. and Marcus, Elizabeth
A and Sachs, George},
title = {The pH-Responsive Regulon of HP0244 (FlgS), the Cytoplasmic Histidine
Kinase of Helicobacter pylori},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {449--460},
number = {2},
month = jan,
abstract = {Helicobacter pylori colonizes the acidic gastric environment, in contrast
to all other neutralophiles, whose acid resistance and tolerance
responses allow only gastric transit. This acid adaptation is dependent
on regulation of gene expression in response to pH changes in the
periplasm and cytoplasm. The cytoplasmic histidine kinase, HP0244,
which until now was thought only to regulate flagellar gene expression
via its cognate response regulator, HP0703, was found to generate
a response to declining medium pH. Although not required for survival
at pH 4.5, HP0244 is required for survival at pH 2.5 with 10 mM urea
after 30 min. Transcriptional profiling of a HP0244 deletion mutant
grown at pH 7.4 confirmed the contribution of HP0244 to {sigma}54
activation via HP0703 to coordinate flagellar biosynthesis by a pH-independent
regulon that includes 14 flagellar genes. Microarray analysis of
cells grown at pH 4.5 without urea revealed an additional 22 genes,
including 4 acid acclimation genes (ureA, ureB, ureI, and amiE) that
are positively regulated by HP0244. Additionally, 86 differentially
expressed genes, including 3 acid acclimation genes (ureF, rocF [arginase],
and ansB [asparaginase]), were found in cells grown at pH 2.5 with
30 mM urea. Hence, HP0244 has, in addition to the pH-independent
flagellar regulon, a pH-dependent regulon, which allows adaptation
to a wider range of environmental acid conditions. An acid survival
study using an HP0703 mutant and an electrophoretic mobility shift
assay with in vitro-phosphorylated HP0703 showed that HP0703 does
not contribute to acid survival and does not bind to the promoter
regions of several genes in the HP0244 pH-dependent regulon, suggesting
that there is a pathway outside the HP0703 regulon which transduces
the acid-responsive signal sensed by HP0244.},
url = {http://jb.asm.org/cgi/content/abstract/191/2/449}
}
@ARTICLE{Wen2007,
author = {Wen, Yi and Feng, Jing and Scott, David R. and Marcus, Elizabeth
A. and Sachs, George},
title = {The HP0165-HP0166 Two-Component System (ArsRS) Regulates Acid-Induced
Expression of HP1186 {alpha}-Carbonic Anhydrase in Helicobacter pylori
by Activating the pH-Dependent Promoter},
journal = {J. Bacteriol.},
year = {2007},
volume = {189},
pages = {2426--2434},
number = {6},
month = mar,
abstract = {The periplasmic {alpha}-carbonic anhydrase of Helicobacter pylori
is essential for buffering the periplasm at acidic pH. This enzyme
is an integral component of the acid acclimation response that allows
this neutralophile to colonize the stomach. Transcription of the
HP1186 {alpha}-carbonic anhydrase gene is upregulated in response
to low environmental pH. A binding site for the HP0166 response regulator
(ArsR) has been identified in the promoter region of the HP1186 gene.
To investigate the mechanism that regulates the expression of HP1186
in response to low pH and the role of the HP0165-HP0166 two-component
system (ArsRS) in this acid-inducible regulation, Northern blot analysis
was performed with RNAs isolated from two different wild-type H.
pylori strains (26695 and 43504) and mutants with HP0165 histidine
kinase (ArsS) deletions, after exposure to either neutral pH or low
pH (pH 4.5). ArsS-dependent upregulation of HP1186 {alpha}-carbonic
anhydrase in response to low pH was found in both strains. Western
blot analysis of H. pylori membrane proteins confirmed the regulatory
role of ArsS in HP1186 expression in response to low pH. Analysis
of the HP1186 promoter region revealed two possible transcription
start points (TSP1 and TSP2) located 43 and 11 bp 5' of the ATG start
codon, respectively, suggesting that there are two promoters transcribing
the HP1186 gene. Quantitative primer extension analysis showed that
the promoter from TSP1 (43 bp 5' of the ATG start codon) is a pH-dependent
promoter and is regulated by ArsRS in combating environmental acidity,
whereas the promoter from TSP2 may be responsible for control of
the basal transcription of HP1186 {alpha}-carbonic anhydrase.},
url = {http://jb.asm.org/cgi/content/abstract/189/6/2426}
}
@ARTICLE{Wen2003,
author = {Wen, Yi and Marcus, Elizabeth A. and Matrubutham, Uday and Gleeson,
Martin A. and Scott, David R. and Sachs, George},
title = {Acid-Adaptive Genes of Helicobacter pylori},
journal = {Infect. Immun.},
year = {2003},
volume = {71},
pages = {5921--5939},
number = {10},
month = oct,
abstract = {Helicobacter pylori is the only neutralophile that has been able to
colonize the human stomach by using a variety of acid-adaptive mechanisms.
One of the adaptive mechanisms is increased buffering due to expression
of an acid-activated inner membrane urea channel, UreI, and a neutral
pH-optimum intrabacterial urease. To delineate other possible adaptive
mechanisms, changes in gene expression in response to acid exposure
were examined using genomic microarrays of H. pylori exposed to different
levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the
absence and presence of 5 mM urea. Gene expression was correlated
with intrabacterial pH measured using 2',7'-bis-(2-carboxyethyl)-5-carboxyfluorescein
and compared to that observed with exposure to 42{degrees}C for 30
min. Microarrays containing the 1,534 open reading frames of H. pylori
strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled
with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial
pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with
urea. About 200 genes were up-regulated and [~]100 genes were down-regulated
at pH 4.5 in the absence of urea, and about half that number changed
in the presence of urea. These genes included pH-homeostatic, transcriptional
regulatory, motility, cell envelope, and pathogenicity genes. The
up-regulation of some pH-homeostatic genes was confirmed by real-time
PCR. There was little overlap with the genes induced by temperature
stress. These results suggest that H. pylori has evolved multifaceted
acid-adaptive mechanisms enabling it to colonize the stomach that
may be novel targets for eliminating infection.},
url = {http://iai.asm.org/cgi/content/abstract/71/10/5921}
}
@ARTICLE{Wen2009a,
author = {Wen, Yang-an and Liu, Ding and Xiao, Yan-yu and Luo, Dan and Dong,
Yu-fang and Zhang, Li-ping},
title = {Enhanced glucose synthesis in three-dimensional hepatocyte collagen
matrix},
journal = {Toxicology in Vitro},
year = {2009},
volume = {23},
pages = {744--747},
number = {4},
month = jun,
abstract = {Three-dimensional (3D) cell culture model offers a unique opportunity
to study hepatocytes that require extracellular matrix to keep the
cells at the differentiated state. In this report, we cultured isolated
mouse hepatocytes in a 3D collagen matrix system and developed a
protocol to measure glucose production at 3 h, 6 h, 18 h and 24 h
after culture. The results demonstrated that hepatocytes cultured
under 3D collagen matrix condition consistently produced glucose
at 240-290 mg/106 cells for up to 24 h. Contrarily, hepatocytes cultured
under traditional monolayer condition produced less than 50 mg/106
cells glucose. We demonstrated higher expression of phosphoenolpyruvate
carboxykinase (PEPCK), a key enzyme for the synthesis of glucose
from pyruvate, and CCAAT/enhancer-binding protein [alpha] (C/EBP[alpha]),
an important liver-specific transcription factor, under the 3D collagen
matrix culture condition in comparison to the monolayer condition.
Thus, the 3D collagen matrix system preserved metabolic function
of hepatocytes and can be used as an in vitro model for studying
hepatocyte glucose production and gluconeogenesis.},
issn = {0887-2333},
keywords = {Three-dimensional hepatocyte matrix, Gluconeogenesis, Glucose synthesis,
Hepatocyte monolayer culture, Phosphoenolpyruvate carboxykinase},
url = {http://www.sciencedirect.com/science/article/B6TCP-4VS405W-1/2/51f1bf52fba3e1f9b0801297af20e473}
}
@ARTICLE{Wen2011c,
author = {Wen, Yang-An and Liu, Ding and Zhou, Qian-Yun and Huang, Shi-Feng
and Luo, Peng and Xiang, Yu and Sun, Shan and Luo, Dan and Dong,
Yu-Fang and Zhang, Li-Ping},
title = {Biliary intervention aggravates cholestatic liver injury, and induces
hepatic inflammation, proliferation and fibrogenesis in BDL mice},
journal = {Experimental and Toxicologic Pathology},
year = {2011},
volume = {63},
pages = {277--284},
number = {3},
month = mar,
abstract = {Obstructive cholestasis occurs in various clinical situations, whose
pathological process is complex and not well known. The present study
was initiated to display the complex and multifaceted pathological
process caused by obstructive cholestasis in bile duct-ligated mice.
Adult mice were bile-duct-ligated or sham-operated, and serum and
liver tissues were collected at the indicated time points. Automatic
biochemical analyzer was used to monitor serum biochemical index;
TUNEL, HE staining, immunohistochemistry and Real-time PCR were employed
to evaluate liver apoptosis, necrosis, inflammation, as well as proliferation
and fibrosis. Our results demonstrated that obstructive cholestasis
led to elevated serum biochemical indicators, with ALT peaking at
day 3, indicative of acute hepatic dysfunction. Meanwhile, the number
of TUNEL-positive cells increased significantly, and by 2 weeks,
mild to moderate necrosis became apparent in BDL mouse livers, which
consequently aggravated hepatic inflammatory responses as was demonstrated
by increased expression of KC-1, MIP-2, ICAM-1 and MPO in BDL mouse
livers. Moreover, proliferative hepatocytes around periportal areas,
manifested by enhanced cell mitosis and elevated expression of proliferative
markers such as PCNA and Ki67, increased significantly after BDL,
while increased CK-19-positive cells in bile ducts indicated bile
duct hyperplasia. By 2 weeks, numerous [alpha]-SMA-positive cells
and Sirius-stained collagen were observed, indicative of hepatic
stellate cells (HSC) activation and fibrogenesis. In conclusion,
biliary intervention led to a multifaceted hepatic pathological process
characterized by aggravated liver injury and inflammatory reaction
with enhanced cellular proliferation and fibrogenesis.},
issn = {0940-2993},
keywords = {Bile duct ligation, Obstructive cholestasis, Proliferation, Inflammatory,
Fibrogenesis},
url = {http://www.sciencedirect.com/science/article/pii/S0940299310000072}
}
@ARTICLE{Wen2011a,
author = {Wen, Yu-Gang and Wang, Quan and Zhou, Chong-Zhi and Yan, Dong-Wang
and Qiu, Guo-Qiang and Yang, Chun and Tang, Hua-Mei and Peng, Zhi-Hai},
title = {Identification and validation of Kallikrein-ralated peptidase 11
as a novel prognostic marker of gastric cancer based on immunohistochemistry},
journal = {Journal of Surgical Oncology},
year = {2011},
volume = {104},
pages = {516--524},
number = {5},
abstract = {Background and ObjectivesIt is important to identify and validate
the differentially expressed genes in gastric cancer to screen diagnostic
and/or prognostic tumor markers.MethodscDNA expression microarray,
gene set enrichment analysis, and bioinformatics approaches were
used to screen the differentially expressed genes between gastric
cancer tissues and adjacent non-cancerous mucosa. A novel candidate
prognostic marker, Kallikrein-related peptidase 11 (KLK11), was validated
in 400 Chinese gastric cancer patients. KLK11 expression in gastric
cancer tissues was detected using real-time PCR and Western blot.
KLK11 protein expression was further analyzed by immunostaining on
tissue microarray, followed with clinicopathological significance
and survival analysis.ResultsKLK11 expression was significantly decreased
in gastric cancer compared with that in normal gastric mucosa (P < 0.001).
Furthermore, KLK11 expression was much lower in poorly differentiated
cancer samples than that in well-differentiated group (P < 0.01).
Survival analysis showed that negative KLK11 expression was associated
with nearly fivefold increased risk of distant metastasis after curative
gastrectomy (HR 4.65, P < 0.01). Multivariate Cox regression
analysis showed that KLK11 expression emerged as a significant independent
prognostic factor for disease-free survival and overall survival
(P < 0.05).ConclusionsThe results indicated that KLK11 expression
was decreased in gastric cancer and might serve as a novel independent
prognostic marker. J. Surg. Oncol. 2011; 104:516–524. © 2011 Wiley-Liss,
Inc.},
doi = {10.1002/jso.21981},
issn = {1096-9098},
keywords = {differentially expressed gene, gastric carcinoma, Kallikrein-related
peptidase 11, microarray, prognosis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jso.21981}
}
@ARTICLE{Wen2010,
author = {Wen, Zhining and Wang, Charles and Shi, Quan and Huang, Ying and
Su, Zhenqiang and Hong, Huixiao and Tong, Weida and Shi, Leming},
title = {Evaluation of gene expression data generated from expired Affymetrix
GeneChip® microarrays using MAQC reference RNA samples},
journal = {BMC Bioinformatics},
year = {2010},
volume = {11},
pages = {S10},
number = {Suppl 6},
abstract = {BACKGROUND:The Affymetrix GeneChip® system is a commonly used platform
for microarray analysis but the technology is inherently expensive.
Unfortunately, changes in experimental planning and execution, such
as the unavailability of previously anticipated samples or a shift
in research focus, may render significant numbers of pre-purchased
GeneChip® microarrays unprocessed before their manufacturer’s expiration
dates. Researchers and microarray core facilities wonder whether
expired microarrays are still useful for gene expression analysis.
In addition, it was not clear whether the two human reference RNA
samples established by the MAQC project in 2005 still maintained
their transcriptome integrity over a period of four years. Experiments
were conducted to answer these questions.RESULTS:Microarray data
were generated in 2009 in three replicates for each of the two MAQC
samples with either expired Affymetrix U133A or unexpired U133Plus2
microarrays. These results were compared with data obtained in 2005
on the U133Plus2 microarray. The percentage of overlap between the
lists of differentially expressed genes (DEGs) from U133Plus2 microarray
data generated in 2009 and in 2005 was 97.44%. While there was some
degree of fold change compression in the expired U133A microarrays,
the percentage of overlap between the lists of DEGs from the expired
and unexpired microarrays was as high as 96.99%. Moreover, the microarray
data generated using the expired U133A microarrays in 2009 were highly
concordant with microarray and TaqMan® data generated by the MAQC
project in 2005.CONCLUSIONS:Our results demonstrated that microarray
data generated using U133A microarrays, which were more than four
years past the manufacturer’s expiration date, were highly specific
and consistent with those from unexpired microarrays in identifying
DEGs despite some appreciable fold change compression and decrease
in sensitivity. Our data also suggested that the MAQC reference RNA
samples, stored at -80°C, were stable over a time frame of at least
four years.},
doi = {10.1186/1471-2105-11-S6-S10},
issn = {1471-2105},
pubmedid = {20946593},
url = {http://www.biomedcentral.com/1471-2105/11/S6/S10}
}
@ARTICLE{Wende2009,
author = {Wende, Andy and Furtwangler, Katarina and Oesterhelt, Dieter},
title = {Phosphate-Dependent Behavior of the Archaeon Halobacterium salinarum
Strain R1},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {3852--3860},
number = {12},
month = jun,
abstract = {Phosphate is essential for life on earth, since it is an integral
part of important biomolecules. The mechanisms applied by bacteria
and eukarya to combat phosphate limitation are fairly well understood.
However, it is not known how archaea sense phosphate limitation or
which genes are regulated upon limitation. We conducted a microarray
analysis to explore the phosphate-dependent gene expression of Halobacterium
salinarum strain R1. We identified a set of 17 genes whose transcript
levels increased up to several hundredfold upon phosphate limitation.
Analysis of deletion mutants showed that this set of genes, the PHO
stimulon, is very likely independent of signaling via two-component
systems. Our experiments further indicate that PHO stimulon induction
might be dependent on the intracellular phosphate concentration,
which turned out to be subject to substantial changes. Finally, the
study revealed that H. salinarum exhibits a phosphate-directed chemotaxis,
which is induced by phosphate starvation.},
url = {http://jb.asm.org/cgi/content/abstract/191/12/3852}
}
@ARTICLE{Wendell2006,
author = {Wendell, Douglas L. and Platts, Adrian and Land, Susan},
title = {Global analysis of gene expression in the estrogen induced pituitary
tumor of the F344 rat},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2006},
volume = {101},
pages = {188--196},
number = {4-5},
month = nov,
abstract = {The F344 rat rapidly forms large prolactinomas in response to chronic
estrogen treatment. To identify genes expressed in the course of
this estrogen induced pituitary tumor growth, we performed microarray
analysis on the F344 rat pituitary after chronic estrogen treatment
and on untreated controls. At a significance level set to minimize
type I error, some 72 genes were found to be differentially expressed
between estrogen treated and untreated. Of those genes, 70 have not
been reported previously as being affected by estrogen in the F344
rat pituitary. Since many other investigators have studied the effect
of estrogen on specific gene expression in rat pituitary, we also
examined the mRNA expression of the 36 genes that have been previously
reported as having their expression affected by estrogen in the rat
pituitary. Of these, 13 were found to have their expression affected
by estrogen treatment in the same direction as had been reported
by others.},
issn = {0960-0760},
keywords = {Estrogen, Pituitary, Gene expression, Fischer 344, Prolactinoma},
url = {http://www.sciencedirect.com/science/article/B6T8X-4M04J1M-1/2/a1f32b0a0c5e178b5467b8c230dfa7f9}
}
@ARTICLE{Wendt2006,
author = {Wendt, Katy and Wilk, Esther and Buyny, Sabine and Buer, Jan and
Schmidt, Reinhold E. and Jacobs, Roland},
title = {Gene and protein characteristics reflect functional diversity of
CD56dim and CD56bright NK cells},
journal = {J. Leukoc. Biol.},
year = {2006},
volume = {80},
pages = {1529--1541},
number = {6},
month = dec,
abstract = {Recent findings underline the role of NK cell subsets in regulating
adaptive immunity. To define characteristics of NK cell subpopulations,
purified CD56dim and CD56bright NK cells were analyzed by using gene
chip arrays covering more than 39,000 transcripts. Gene profiling
revealed resting NK cells to differ in respect to 473 transcripts
with 176 exclusively expressed in CD56dim and 130 solely in CD56bright
NK cells. Results were compared with array analyses using mRNA obtained
from activated CD56dim and CD56bright NK cells. In this approach,
NK cell receptors, cytolytic molecules, adhesion structures, and
chemokine ligands showed differential expression patterns in the
two subpopulations. These data were validated using FACS, RT-qPCR,
or cytokine bead array (CBA) techniques. Cytokines produced by CD56dim
and CD56bright NK cells were determined using a protein array covering
79 different bioactive mediators. GDNF, IGFBP-1, EGF, and TIMP-2
were detected in both subsets. In contrast, IGFBP-3 and IGF-1 were
mainly produced by CD56dim, while GM-CSF, TARC, and TGF{beta}3 were
expressed by CD56bright NK cells. In summary, we report new characteristic
features of CD56dim and CD56bright NK cells, further underscoring
that they represent independent populations with functionally diverse
capabilities. The information on NK cells generated in this study
will help to define corresponding NK cell populations in other species
that lack CD56 expression on NK cells, such as mice. This will subsequently
lead to the establishment of suitable animal models for detailed
analysis of NK cell populations in vivo.},
url = {http://www.jleukbio.org/cgi/content/abstract/80/6/1529}
}
@ARTICLE{Weng2010,
author = {Weng, Lihong and Wu, Xiwei and Gao, Hanlin and Mu, Bing and Li, Xuejun
and Wang, Jin-Hui and Guo, Chao and Jin, Jennifer M and Chen, Zhuo
and Covarrubias, Maricela and Yuan, Yate-Ching and Weiss, Lawrence
M and Wu, Huiqing},
title = {MicroRNA profiling of clear cell renal cell carcinoma by whole-genome
small RNA deep sequencing of paired frozen and formalin-fixed, paraffin-embedded
tissue specimens},
journal = {J. Pathol.},
year = {2010},
volume = {222},
pages = {41--51},
number = {1},
abstract = {Abstract 10.1002/path.2736.abs Renal cell carcinoma (RCC) is one of
the leading causes of cancer mortality. Characterization of microRNA
(miRNA) expression of RCC will help disclose new pathogenic pathways
in tumourigenesis and progression and may lead to the development
of molecular biomarkers and target-specific therapies for diagnosis,
prognostication and treatment. With limitations in test specificity
and the ability to detect novel miRNA and other small non-coding
RNAs (smRNAs), microarray and RT–PCR techniques are being replaced
by the evolving deep-sequencing technologies, at least in the discovery
phase. Until now, cancer miRNA profiling of human benign and tumour
specimen sets, using smRNA deep-sequencing (smRNA-seq), has not been
reported. Specifically, due to concern over possible poor RNA quality/integrity,
formalin-fixed paraffin-embedded (FFPE) samples have not been used
for such studies. Here, we performed whole-genome smRNA-seq analysis
using a benign and RCC specimen set and have successfully profiled
the miRNA expression. Studies performed on paired frozen and FFPE
specimens showed very similar results. Moreover, a comparison study
of microarray, deep-sequencing and RT–PCR methodologies also showed
a high correlation among the three technologies. To our knowledge,
this is the first study to demonstrate that FFPE specimens can be
used reliably for miRNA deep-sequencing analysis, making future large-scale
clinical cohort/trial-based studies possible. Copyright © 2010 Pathological
Society of Great Britain and Ireland. Published by John Wiley & Sons,
Ltd.},
issn = {1096-9896},
keywords = {miRNA, renal cell carcinoma, formalin-fixed paraffin-embedded (FFPE),
small RNA deep sequencing (smRNA-seq), next-generation sequencing,
microarray, RT–PCR},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2736}
}
@ARTICLE{Wenger2011,
author = {Wenger, Karl H. and El-Awady, Ahmed R. and Messer, Regina L. W. and
Sharawy, Mohamed M. and White, Greg and Lapp, Carol A.},
title = {Pneumatic pressure bioreactor for cyclic hydrostatic stress application:
mechanobiology effects on periodontal ligament cells},
journal = {J Appl Physiol},
year = {2011},
volume = {111},
pages = {1072-1079},
number = {4},
abstract = {A bioreactor system was developed to provide high-amplitude cyclic
hydrostatic compressive stress (cHSC) using compressed air mixed
commercially as needed to create partial pressures of oxygen and
carbon dioxide appropriate for the cells under investigation. Operating
pressures as high as 300 psi are achievable in this system at cyclic
speeds of up to 0.2 Hz. In this study, ligamentous fibroblasts from
human periodontal ligaments (n = 6) were compressed on two consecutive
days at 150 psi for 3 h each day, and the mRNA for families of extracellular
matrix protein and protease isoforms was evaluated by real-time PCR
array. Several integrins were significantly upregulated, most notably
alpha-3 (6.4-fold), as was SPG7 (12.1-fold). Among the collagens,
Col8a1 was highly upregulated at 53.5-fold, with Col6a1, Col6a2,
and Col7a1 also significantly upregulated 4.4- to 8.5-fold. MMP-1
was the most affected at 122.9-fold upregulation. MMP-14 likewise
increased 17.8-fold with slight reductions for the gelatinases and
a significant increase of TIMP-2 at 5.8-fold. The development of
this bioreactor system and its utility in characterizing periodontal
ligament fibroblast mechanobiology in intermediate-term testing hold
promise for better simulating the conditions of the musculoskeletal
system and the large cyclic compressive stresses joints may experience
in gait, exertion, and mastication.},
doi = {10.1152/japplphysiol.01175.2010},
eprint = {http://jap.physiology.org/cgi/reprint/111/4/1072.pdf},
url = {http://jap.physiology.org/cgi/content/abstract/111/4/1072}
}
@ARTICLE{Weniger2011,
author = {Weniger, Marc A. and Rizzatti, Edgar G. and Perez-Galan, Patricia
and Liu, Delong and Wang, Qiuyan and Munson, Peter J. and Raghavachari,
Nalini and White, Therese and Tweito, Megan M. and Dunleavy, Kieron
and Ye, Yihong and Wilson, Wyndham H. and Wiestner, Adrian},
title = {Treatment-Induced Oxidative Stress and Cellular Antioxidant Capacity
Determine Response to Bortezomib in Mantle Cell Lymphoma},
journal = {Clin. Cancer Res.},
year = {2011},
volume = {17},
pages = {5101-5112},
number = {15},
abstract = {Purpose: Proteasome inhibition disrupts protein homeostasis and induces
apoptosis. Up to 50% of patients with relapsed mantle cell lymphoma
(MCL) respond to bortezomib. We used gene expression profiling to
investigate the connection between proteasome inhibition, cellular
response, and clinical efficacy. Experimental Design: We assessed
transcriptional changes in primary tumor cells from five patients
during treatment with bortezomib in vivo, and in 10 MCL cell lines
exposed to bortezomib in vitro, on Affymetrix microarrays. Key findings
were confirmed by western blotting. Results: MCL cell lines exposed
to bortezomib in vitro showed upregulation of endoplasmic reticulum
and oxidative stress response pathways. Gene expression changes were
strongest in bortezomib-sensitive cells and these cells were also
more sensitive to oxidative stress induced by H2O2. Purified tumor
cells obtained at several timepoints during bortezomib treatment
in 5 previously untreated patients with leukemic MCL showed strong
activation of the antioxidant response controlled by NRF2. Unexpectedly,
activation of this homeostatic program was significantly stronger
in tumors with the best clinical response. Consistent with its proapoptotic
function, we found upregulation of NOXA in circulating tumor cells
of responding patients. In resistant cells, gene expression changes
in response to bortezomib were limited and upregulation of NOXA was
absent. Interestingly, at baseline, bortezomib-resistant cells displayed
a relatively higher expression of the NRF2 gene-expression signature
than sensitive cells (P < 0.001). Conclusion: Bortezomib triggers
an oxidative stress response in vitro and in vivo. High cellular
antioxidant capacity contributes to bortezomib resistance. Clin Cancer
Res; 17(15); 5101-12. (C)2011 AACR.},
doi = {10.1158/1078-0432.CCR-10-3367},
eprint = {http://clincancerres.aacrjournals.org/cgi/reprint/17/15/5101.pdf},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/17/15/5101}
}
@ARTICLE{Wenke2011,
author = {Wenke, Katrin and Wanke, Dierk and Kilian, Joachim and Berendzen,
Kenneth and Harter, Klaus and Piechulla, Birgit},
title = {Volatiles of two growth-inhibiting rhizobacteria commonly enroll
AtWRKY18 function},
journal = {The Plant Journal},
year = {2011},
pages = {no--no},
abstract = {Interactions with the (a)biotic environment play key roles for plant’s
fitness and vitality. In addition to direct surface-to-surface contact,
volatile chemicals also affect other organisms. Volatiles of Serratia
plymuthica and Stenotrophomonas maltophilia significantly inhibited
growth and induced H2O2 production in Arabidopsis in dual-culture.
Within one day, transcriptional changes could be observed by promoter-GUS
assays using a stress inducible, W-box containing 4xGST1 construct.
Expression studies performed at 6, 12 and 24 hours revealed altered
transcript levels for 889 or 655 genes in response to S. plymuthica
or S. maltophilia volatiles, respectively. Expression of 162 genes
was altered in both treatments. Meta analysis revealed specifically
volatile-responsive genes to be most similar to abiotic stress responses.
For these volatile specific responses we introduce the term mVAMP
(microbial Volatile-Associated Molecular Pattern). Genes responsive
to both treatments were enriched for W-box motifs in their promoters
and were significantly enriched for transcription factors (ERF2,
ZAT10, MYB73 and WRKY18). Susceptibility of WRKY18 mutant lines was
significantly delayed, which suggests an indispensable role for WRKY18
in bacterial volatile responses.© 2011 The Authors. The Plant Journal©
2011 Blackwell Publishing Ltd},
doi = {10.1111/j.1365-313X.2011.04891.x},
issn = {1365-313X},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2011.04891.x}
}
@ARTICLE{Wennmalm2007,
author = {Wennmalm, Kristian and Calza, Stefano and Ploner, Alexander and Hall,
Per and Bjöhle, Judith and Klaar, Sigrid and Smeds, Johanna and
Pawitan, Yudi and Bergh, Jonas},
title = {Gene expression in 16q is associated with survival and differs between
Sørlie breast cancer subtypes},
journal = {Genes Chromosom. Cancer},
year = {2007},
volume = {46},
pages = {87--97},
number = {1},
abstract = {Abstract 10.1002/gcc.20392.abs We have investigated the relationship
between gene expression and chromosomal positions in 402 breast cancer
patients. Using an overrepresentation approach based on Fisher's
exact test, we identified disproportionate contributions of specific
chromosomal positions to genes associated with survival. Our major
finding is that the gene expression in the long arm of chromosome
16 stands out in its relationship to survival. This arm contributes
36 (18%) and 55 (11%) genes to lists negatively associated with recurrence-free
survival (set to sizes 200 and 500). This is a highly disproportionate
contribution from the 313 (2%) genes in this arm represented on the
used Affymetrix U133A and B microarray platforms (Bonferroni corrected
Fisher test: P < 2.2 × 10−16). We also demonstrate differential
expression in 16q across tumor subtypes, which suggests that the
ERBB2, basal, and luminal B tumors progress along a high grade–poor
prognosis path, while luminal A and normal-like tumors progress along
a low grade–good prognosis path, in accordance with a previously
proposed model of tumor progression. We conclude that important biological
information can be extracted from gene expression data in breast
cancer by studying non-random connections between chromosomal positions
and gene expression. This article contains Supplementary Material
available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
© 2006 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20392}
}
@ARTICLE{Wens2011,
author = {B. Wens and P. De Boever and M. Maes and K. Hollanders and G. Schoeters},
title = {Transcriptomics identifies differences between ultrapure non-dioxin-like
polychlorinated biphenyls (PCBs) and dioxin-like PCB126 in cultured
peripheral blood mononuclear cells},
journal = {Toxicology},
year = {2011},
volume = {287},
pages = {113 - 123},
number = {1–3},
abstract = {Polychlorinated biphenyls (PCBs) remain ubiquitously present in human
lipids despite the ban on their production and use. Their presence
can be chemically monitored in peripheral blood samples of the general
population. We tested whether in vitro exposure to different PCB
congeners induced different gene expression profiles in peripheral
blood cells. We have isolated peripheral blood mononuclear cells
(PBMC) from whole blood of 8 healthy individuals and exposed these
cells in vitro to individual non-dioxin-like (NDL)-PCB congeners
(PCB52, 138 or 180; 10 μM) or dioxin-like (DL)-PCB congener
PCB126 (1 μM) during 18 h. Differential gene expression
response was measured using Agilent whole-human genome microarrays.
Two-way ANOVA analysis of the data showed that both gender and PCB
exposure are important factors influencing gene expression responses
in blood cells. Hierarchical cluster analysis of genes influenced
by PCB exposure, revealed that DL-PCB126 induced a different gene
expression response compared to the NDL-PCBs. Biological interpretation
of the results revealed that exposure to PCB126 induced the AhR signaling
pathway, whereas the induction of nuclear receptor pathways by the
NDL-PCBs was limited in blood cells. Nevertheless, molecular responses
of blood cells to individual PCB congeners revealed significantly
expressed genes that play a role in biological functions and processes
known to be affected by PCB exposure in vivo. Observed gene expression
changes in this in vitro model were found to be related to hepatotoxicity,
immune and inflammatory response and disturbance of lipid and cholesterol
homeostasis.},
doi = {10.1016/j.tox.2011.06.004},
issn = {0300-483X},
keywords = {Polychlorinated biphenyl (PCB)},
url = {http://www.sciencedirect.com/science/article/pii/S0300483X11002174}
}
@ARTICLE{Wensaas2009,
author = {Wensaas, A. J. and Rustan, A. C. and Rokling-Andersen, M. H. and
Caesar, R. and Jensen, J. and Kaalhus, O. and Graff, B. A. and Gudbrandsen,
O. A. and Berge, R. K. and Drevon, C. A.},
title = {Dietary supplementation of tetradecylthioacetic acid increases feed
intake but reduces body weight gain and adipose depot sizes in rats
fed on high-fat diets},
journal = {Diabetes, Obesity and Metabolism},
year = {2009},
volume = {11},
pages = {1034--1049},
number = {11},
abstract = {Aim: The pan-peroxisome proliferator-activated receptor (PPAR) ligand
and fatty acid analogue tetradecylthioacetic acid (TTA) may reduce
plasma lipids and enhance hepatic lipid metabolism, as well as reduce
adipose tissue sizes in rats fed on high-fat diets. This study further
explores the effects of TTA on weight gain, feed intake and adipose
tissue functions in rats that are fed a high-fat diet for 7 weeks.
Methods: The effects on feed intake and body weight during 7 weeks'
dietary supplement with TTA (∼200 mg/kg bw) were studied in male
Wistar rats fed on a lard-based diet containing ∼40% energy from
fat. Adipose tissue mass, body composition and expression of relevant
genes in fat depots and liver were measured at the end of the feeding.
Results: Despite higher feed intake during the final 2 weeks of the
study, rats fed on TTA gained less body weight than lard-fed rats
and had markedly decreased subcutaneous, epididymal, perirenal and
mesenteric adipose depots. The effects of TTA feeding with reduced
body weight gain and energy efficiency (weight gain/feed intake)
started between day 10 and 13. Body contents of fat, protein and
water were reduced after feeding lard plus TTA, with a stronger decrease
in fat relative to protein. Plasma lipids, including Non-Esterified
Fatty Acids (NEFA), were significantly reduced, whereas fatty acid
β-oxidation in liver and heart was enhanced in lard plus TTA-fed
rats. Hepatic UCP3 was expressed ectopically both at protein and
mRNA level (>1900-fold), whereas Ucp1 mRNA was increased ∼30-fold
in epididymal and ∼90-fold in mesenteric fat after lard plus TTA
feeding. Conclusion: Our data support the hypothesis that TTA feeding
may increase hepatic fatty acid β-oxidation, and thereby reduce
the size of adipose tissues. The functional importance of ectopic
hepatic UCP3 is unknown, but might be associated with enhanced energy
expenditure and thus the reduced feed efficiency.},
issn = {1463-1326},
keywords = {adipose tissue, body weight, energy expenditure, feed intake, pan-PPAR
agonist, tetradecylthioacetic acid},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1463-1326.2009.01092.x}
}
@ARTICLE{Wenter2010,
author = {Wenter, Roland and Hütz, Katharina and Dibbern, Dörte and Li, Tao
and Reisinger, Veronika and Plöscher, Matthias and Eichacker, Lutz
and Eddie, Brian and Hanson, Thomas and Bryant, Donald A. and Overmann,
Jörg},
title = {Expression-based identification of genetic determinants of the bacterial
symbiosis ‘Chlorochromatium aggregatum’},
journal = {Environmental Microbiology},
year = {2010},
volume = {12},
pages = {2259--2276},
number = {8},
abstract = {Summary The phototrophic consortium ‘Chlorochromatium aggregatum’
is a highly structured association of green sulfur bacterial epibionts
surrounding a central, motile bacterium and is the most specific
symbiosis currently known between two phylogenetically distinct bacterial
species. Genes and gene products potentially involved in the symbiotic
interaction were identified on the genomic, transcriptomic and proteomic
level. As compared with the 11 available genomes of free-living relatives,
only 186 open reading frames were found to be unique to the epibiont
genome. 2-D differential gel electrophoresis (2-D DIGE) of the soluble
proteomes recovered 1612 protein spots of which 54 were detected
exclusively in consortia but not in pure epibiont cultures. Using
mass spectrometry analyses, the 13 most intense of the 54 spots could
be attributed to the epibiont. Analyses of the membrane proteins
of consortia, of consortia treated with cross-linkers and of pure
cultures indicated that a branched chain amino acid ABC-transporter
binding protein is only expressed in the symbiotic state of the epibiont.
Furthermore, analyses of chlorosomes revealed that an uncharacterized
11Â kDa epibiont protein is only expressed during symbiosis. This
protein may be involved in the intracellular sorting of chlorosomes.
Application of a novel prokaryotic cDNA suppression subtractive hybridization
technique led to identification of 14 differentially regulated genes,
and comparison of the transcriptomes of symbiotic and free-living
epibionts indicated that 328 genes were differentially transcribed.
The three approaches were mostly complementary and thereby yielded
a first inventory of 352 genes that are likely to be involved in
the bacterial interaction in ‘C. aggregatum’. Notably, most of
the regulated genes encoded components of central metabolic pathways
whereas only very few (7.5%) of the unique ‘symbiosis genes’
turned out to be regulated under the experimental conditions tested.
This pronounced regulation of central metabolic pathways may serve
to fine-tune the symbiotic interaction in ‘C. aggregatum’ in
response to environmental conditions.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2010.02206.x}
}
@ARTICLE{Wenz2010a,
author = {Wenz, Christian and Marchetti-Deschmann, Martina and Herwig, Ela
and Schröttner, Evita and Allmaier, Günter and Trojer, Lukas and
Vollmer, Martin and Rüfer, Andreas},
title = {A fluorescent derivatization method of proteins for the detection
of low-level impurities by microchip capillary gel electrophoresis},
journal = {ELECTROPHORESIS},
year = {2010},
volume = {31},
pages = {611--617},
number = {4},
abstract = {Abstract 10.1002/elps.200900346.abs A novel pre-chip fluorescent derivatization
method is presented for protein sizing and quantification by microchip
CGE. The derivatization reaction employed a water-soluble and stable
fluorescent dye and was performed under conditions that favored the
formation of homogeneous reaction products. The method delivered
in terms of protein sizing similar results as microchip CGE with
on-chip staining but showed an extended linear dynamic range for
protein quantification encompassing four orders of magnitude. The
sensitivity of the method was similar to standard silver-stained
planar gels. The characterization of derivatization reaction products
by MS and preparative isoelectric focusing indicated that a constant
degree of dye molecule tagging was obtained over a broad range of
protein/dye ratios. The method allowed detecting and quantifying
an impurity spiked into an antibody preparation down to a level of
0.05%. Advantages of this method compared with CGE approaches with
pre-column derivatization include a shorter analysis time and an
increased robustness and ease of use.},
issn = {1522-2683},
keywords = {CE-SDS, LIF, Microchip, Quality screening, SDS gel},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200900346}
}
@ARTICLE{Wenz2009,
author = {Wenz, Christian and Rüfer, Andreas},
title = {Microchip CGE linked to immunoprecipitation as an alternative to
Western blotting},
journal = {ELECTROPHORESIS},
year = {2009},
volume = {30},
pages = {4264--4269},
number = {24},
abstract = {Abstract 10.1002/elps.200900347.abs A novel approach for protein identification
is presented, which combines the specificity of an immunoprecipitation
approach with the sensitivity of protein detection in microchip CGE.
This method involves derivatization of the sample proteins with a
fluorescent dye, target protein isolation with specific antibodies
and Protein A coated magnetic beads, and automated sizing and quantification
of the eluted samples on microchips. The performance of the new technique
was demonstrated with glutathion-S-transferase- and polyHistidine-tagged
target proteins in an Escherichiacoli background. A specific detection
of target proteins was possible down to 0.001% or 1 ng target protein
in a background of 100 μg E. coli protein. With this approach,
proteins ranging from 10 to 220 kDa could be identified with a
panel of different target-specific antibodies. The reproducibility
of the method was very similar to standard microchip CGE methods.
In a direct comparison to Western blotting, a similar sensitivity
and specificity of both techniques was observed. However, the new
approach compares favorably to Western blotting in terms of time-to-result,
usability and labor intensity, antibody consumption and access to
quantitative data.},
issn = {1522-2683},
keywords = {CE-SDS, Immunoaffinity, Laser-induced fluorescence, Microchip, SDS
gel},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200900347}
}
@ARTICLE{Wenz2010,
author = {Wenz, C. and Salowsky, R. and Herwig, E. and Marchetti-Deschmann,
M. and Allmaier, G. and Ruefer, A.},
title = {Specific detection of proteins by immunoprecipitation combined with
high sensitivity protein sizing on microchips},
journal = {New Biotechnology},
year = {2010},
volume = {27},
pages = {S74--S75},
number = {Supplement 1},
month = apr,
booktitle = {Abstracts of the 4th ESF Conference on Functional Genomics \& Disease,
14-17 April 2010, Dresden, Germany},
issn = {1871-6784},
url = {http://www.sciencedirect.com/science/article/B8JG4-4YM4WNS-6G/2/85f9262e41d741db959bc94d810835e8}
}
@ARTICLE{Wenzel2008,
author = {Wenzel, Joerg and Tomiuk, Stefan and Zahn, Sabine and Küsters, Daniel
and Vahsen, Anja and Wiechert, Andreas and Mikus, Sandra and Birth,
Michael and Scheler, Marina and von Bubnoff, Dagmar and Baron, Jens
M. and Merk, Hans F. and Mauch, Cornelia and Krieg, Thomas and Bieber,
Thomas and Bosio, Andreas and Hofmann, Kay and Tüting, Thomas and
Peters, Bettina},
title = {Transcriptional profiling identifies an interferon-associated host
immune response in invasive squamous cell carcinoma of the skin},
journal = {Int. J. Cancer},
year = {2008},
volume = {123},
pages = {2605--2615},
number = {11},
abstract = {Abstract 10.1002/ijc.23799.abs Squamous cell carcinoma (SCC) and basal
cell carcinoma (BCC) represent the 2 most common types of nonmelanoma
skin cancer. Both derive from keratinocytes but show a distinct biological
behavior. Here we present transcriptional profiling data of a large
cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially
expressed genes reflect known features of SCC and BCC including the
typical cytokeratin pattern as well as upregulation of characteristic
cell proliferation genes. Additionally, we found increased expression
of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1,
IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression
of IFN-regulated genes correlated with the extent of the lesional
immune-cell infiltrate. Immunohistological examinations confirmed
the expression of IFN-regulated genes in association with a CXCR3+
cytotoxic inflammatory infiltrate on the protein level. Of note,
a small subset of SCC samples with low expression of IFN-regulated
genes included most organ transplant recipients receiving immunosuppressive
medication. Collectively, our findings support the concept that IFN-associated
host responses play an important role in tumor immunosurveillance
in the skin. © 2008 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {skin, interferon, chemokine, cancer, immunosurveil-lance, Lupus, SLE},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23799}
}
@ARTICLE{Wenzlau2007,
author = {Wenzlau, Janet M. and Juhl, Kirstine and Yu, Liping and Moua, Ong
and Sarkar, Suparna A. and Gottlieb, Peter and Rewers, Marian and
Eisenbarth, George S. and Jensen, Jan and Davidson, Howard W. and
Hutton, John C.},
title = {The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen
in human type 1 diabetes},
journal = {PNAS},
year = {2007},
volume = {104},
pages = {17040--17045},
number = {43},
month = oct,
abstract = {Type 1 diabetes (T1D) results from progressive loss of pancreatic
islet mass through autoimmunity targeted at a diverse, yet limited,
series of molecules that are expressed in the pancreatic {beta} cell.
Identification of these molecular targets provides insight into the
pathogenic process, diagnostic assays, and potential therapeutic
agents. Autoantigen candidates were identified from microarray expression
profiling of human and rodent pancreas and islet cells and screened
with radioimmunoprecipitation assays using new-onset T1D and prediabetic
sera. A high-ranking candidate, the zinc transporter ZnT8 (Slc30A8),
was targeted by autoantibodies in 60-80% of new-onset T1D compared
with <2% of controls and <3% type 2 diabetic and in up to 30% of
patients with other autoimmune disorders with a T1D association.
ZnT8 antibodies (ZnTA) were found in 26% of T1D subjects classified
as autoantibody-negative on the basis of existing markers [glutamate
decarboxylase (GADA), protein tyrosine phosphatase IA2 (IA2A), antibodies
to insulin (IAA), and islet cytoplasmic autoantibodies (ICA)]. Individuals
followed from birth to T1D showed ZnT8A as early as 2 years of age
and increasing levels and prevalence persisting to disease onset.
ZnT8A generally emerged later than GADA and IAA in prediabetes, although
not in a strict order. The combined measurement of ZnT8A, GADA, IA2A,
and IAA raised autoimmunity detection rates to 98% at disease onset,
a level that approaches that needed to detect prediabetes in a general
pediatric population. The combination of bioinformatics and molecular
engineering used here will potentially generate other diabetes autoimmunity
markers and is also broadly applicable to other autoimmune disorders.},
url = {http://www.pnas.org/cgi/content/abstract/104/43/17040}
}
@ARTICLE{Werling2008,
author = {Werling, József and Kocsis, Béla and Dean, Diane and Kustos, Ildikó},
title = {Characterisation of protein composition and detection of IgA in cervicovaginal
fluid by microchip technology},
journal = {Journal of Chromatography B},
year = {2008},
volume = {869},
pages = {54--58},
number = {1-2},
month = jun,
abstract = {In this paper the application of microchip electrophoresis to examine
the protein profile of cervicovaginal fluid and the detection of
IgA heavy and light chains is presented. This method is a fast growing
field of technology and ensures high-speed analysis requiring only
microliters of sample. Proteins with wide range of molecular masses
could be separated within 1 min. Cervicovaginal specimens of healthy
women showed a complex protein pattern-containing several peaks in
the 15-70 kDa region. sIgA is considered to be an important protein
constituent of all mucosal surfaces. Detection of sIgA in cervicovaginal
samples was achievable by microchip technology. Under reduced circumstances
(induced by mercaptoethanol, a component of the denaturating solution)
the disulfide bonds connecting IgA heavy and light chains are broken
up and chains can be detected as separate peaks during electrophoresis.
In 82.5% of the cases only the light chain of IgA could be detected
in the clinical samples. The intact IgA heavy chain could be demonstrated
in only 12.5% of the cases. Based on our data some conclusions were
provided about the correlation of these patterns with the age of
patients, pH of the cervicovaginal fluid, operations performed before
sample collection and usage of oral contraceptives.},
issn = {1570-0232},
keywords = {Microchip electrophoresis, Cervicovaginal fluid, Protein, IgA},
url = {http://www.sciencedirect.com/science/article/B6X0P-4SHMCJX-1/2/2660faad3d4900112a6d11315f081c9b}
}
@ARTICLE{Werner2004,
author = {Werner, Guido and Strommenger, Birgit and Klare, Ingo and Witte,
Wolfgang},
title = {Molecular Detection of Linezolid Resistance in Enterococcus faecium
and Enterococcus faecalis by Use of 5' Nuclease Real-Time PCR Compared
to a Modified Classical Approach},
journal = {J. Clin. Microbiol.},
year = {2004},
volume = {42},
pages = {5327--5331},
number = {11},
month = nov,
abstract = {A nucleotide transversion from guanine to uracil in the 23S rRNA confers
linezolid resistance. We describe a real-time PCR using two Taqman
probes that detects a single mutated allele among the genomes of
Enterococcus faecium and Enterococcus faecalis. Results were confirmed
by a classical approach involving LabChip technology assayed with
an Agilent Bioanalyzer 2100.},
url = {http://jcm.asm.org/cgi/content/abstract/42/11/5327}
}
@ARTICLE{Werner2007,
author = {Werner, Hauke B. and Kuhlmann, Katja and Shen, Siming and Uecker,
Marina and Schardt, Anke and Dimova, Kalina and Orfaniotou, Foteini
and Dhaunchak, Ajit and Brinkmann, Bastian G. and Mobius, Wiebke
and Guarente, Lenny and Casaccia-Bonnefil, Patrizia and Jahn, Olaf
and Nave, Klaus-Armin},
title = {Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS
Myelin},
journal = {J. Neurosci.},
year = {2007},
volume = {27},
pages = {7717--7730},
number = {29},
month = jul,
abstract = {Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes
provide a genuine model for spastic paraplegia (SPG-2). Their axons
are well myelinated but exhibit impaired axonal transport and progressive
degeneration, which is difficult to attribute to the absence of a
single myelin protein. We hypothesized that secondary molecular changes
in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection
and provide more insight into glia-axonal interactions in this disease
model. By gel-based proteome analysis, we identified >160 proteins
in purified myelin membranes, which allowed us to systematically
monitor the CNS myelin proteome of adult PLPnull mice, before the
onset of disease. We identified three proteins of the septin family
to be reduced in abundance, but the nicotinamide adenine dinucleotide
(NAD+)-dependent deacetylase sirtuin 2 (SIRT2) was virtually absent.
SIRT2 is expressed throughout the oligodendrocyte lineage, and immunoelectron
microscopy revealed its association with myelin. Loss of SIRT2 in
PLPnull was posttranscriptional, suggesting that PLP/DM20 is required
for its transport into the myelin compartment. Because normal SIRT2
activity is controlled by the NAD+/NADH ratio, its function may be
coupled to the axo-glial metabolism and the long-term support of
axons by oligodendrocytes.},
url = {http://www.jneurosci.org/cgi/content/abstract/27/29/7717}
}
@ARTICLE{Werner2009,
author = {Werner, Jeffrey J. and Ptak, A. Celeste and Rahm, Brian G. and Zhang,
Sheng and Richardson, Ruth E.},
title = {Absolute quantification of Dehalococcoides proteins: enzyme bioindicators
of chlorinated ethene dehalorespiration},
journal = {Environmental Microbiology},
year = {2009},
volume = {11},
pages = {2687--2697},
number = {10},
abstract = {Summary The quantification of trace proteins in complex environmental
samples and mixed microbial communities would be a valuable monitoring
tool in countless applications, including the bioremediation of groundwater
contaminated with chlorinated solvents. Measuring the concentrations
of specific proteins provides unique information about the activity
and physiological state of organisms in a sample. We developed sensitive
(<Â 5Â fmol), selective bioindicator assays for the absolute quantification
of select proteins used by Dehalococcoides spp. when reducing carbon
atoms in the common pollutants trichloroethene (TCE) and tetrachloroethene
(PCE). From complex whole-sample digests of two different dechlorinating
mixed communities, we monitored the chromatographic peaks of selected
tryptic peptides chosen to represent 19 specific Dehalococcoides
proteins. This was accomplished using multiple-reaction monitoring
(MRM) assays using nano-liquid chromatography-tandem mass spectrometry
(nLC-MS/MS), which provided the selectivity, sensitivity and reproducibility
required to quantify Dehalococcoides proteins in complex samples.
We observed reproducible peak areas (average CVÂ =Â 0.14 over 4Â days,
n = 3) and linear responses in standard curves (n = 5, R2 > 0.98)
using synthetic peptide standards spiked into a background matrix
of sediment peptides. We detected and quantified TCE reductive dehalogenase
(TceA) at 7.6 ± 1.7 × 103 proteins cell−1 in the KB1TM bioaugmentation
culture, previously thought to be lacking TceA. Fragmentation data
from MS/MS shotgun proteomics experiments were helpful in developing
the MRM targets. Similar shotgun proteomics data are emerging in
labs around the world for many environmentally relevant microbial
proteins, and these data are a valuable resource for the future development
of MRM assays. We expect targeted peptide quantification in environmental
samples to be a useful tool in environmental monitoring.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2009.01996.x}
}
@ARTICLE{Wescombe2010,
author = {Wescombe, Leon and Lahooti, Hooshang and Gopinath, Bamini and Wall,
Jack R.},
title = {The cardiac calsequestrin gene (CASQ2) is up-regulated in the thyroid
in patients with Graves’ ophthalmopathy – support for a role
of autoimmunity against calsequestrin as the triggering event},
journal = {Clinical Endocrinology},
year = {2010},
volume = {73},
pages = {522--528},
number = {4},
abstract = {Summary Background Graves’ Ophthalmopathy (GO) is a complex eye
and orbital disorder that is uniquely linked to Graves’ Hyperthyroidism
(GH) and has traditionally been considered a cross-reactive immune
response against the thyroid stimulating hormone receptor (TSHR)
in orbital tissue. However, because there is no direct evidence,
such as specific TSHR antibodies or T lymphocytes targeting the orbital
tissues in patients with GO compared to those without eye disease,
it is important to consider alternative hypotheses for the pathogenesis
of GO. The aim of this study was to identify differentially expressed
genes within the thyroid of patients with GO and GH as a possible
explanation for a thyroid initiated orbital autoimmunity. MethodsÂ
RNA was extracted from thyroid glands of patients with GO (n = 10)
and GH (n = 8) post-total thyroidectomy. RNA samples were arrayed
on Illumina® Human Ref-8 Expression BeadChips™ representing 20 589
genes. Microarray results of selected genes were validated by quantitative
PCR (qPCR) and levels of protein translation measured by Western
blot analysis. Findings Two hundred and nighty-five genes were
differentially expressed between patients with GO and GH. Of these,
the cardiac calsequestrin gene (CASQ2) was the most highly expressed
gene in GO (2·2-fold increase, P < 0·05). The succinate dehydrogenase
flavoprotein subunit gene (SDHA) was also significantly up-regulated
in GO (P < 0·05), 1·4-fold, while genes encoding the thyroid
antigens thyroglobulin, thyroid peroxidase and TSHR were not differentially
expressed. qPCR verified up-regulation of CASQ2 and down-regulation
BMP7, CD80, IGFBP5, and MYD88 genes in GO. Western blot analysis
showed that the average CASQ/GAPDH protein expression ratios for
GH and GO were 1·04 and 1·03, respectively. t-Test analysis of
data generated a P-value of 0·26, therefore no significant difference
was found for CASQ protein expression in thyroid tissue between GH
and GO. Interpretation The skeletal and cardiac calsequestrin proteins
share 68·4% amino acid homology. Previous work has shown that RNA
levels of skeletal muscle calsequestrin are 4·7 times higher in
extraocular muscle (EOM) than in masticatory skeletal muscle (jaw),
and cardiac calsequestrin is expressed 2·7 times more in EOM. We
postulate that up-regulation of casq2 gene in the thyroid of patients
with GH may lead to the production of autoantibodies and sensitized
T-lymphocytes, which cross-react with calsequestrin in the EOM of
patients who develop ophthalmopathy.},
issn = {1365-2265},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2265.2009.03753.x}
}
@ARTICLE{Wesolowska2011,
author = {Wesolowska, A and Dalgaard, M D and Borst, L and Gautier, L and Bak,
M and Weinhold, N and Nielsen, B F and Helt, L R and Audouze, K and
Nersting, J and Tommerup, N and Brunak, S and Sicheritz-Ponten, T
and Leffers, H and Schmiegelow, K and Gupta, R},
title = {Cost-effective multiplexing before capture allows screening of 25[thinsp]000
clinically relevant SNPs in childhood acute lymphoblastic leukemia},
journal = {Leukemia},
year = {2011},
pages = {--},
month = mar,
issn = {1476-5551},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/leu.2011.32}
}
@ARTICLE{Wesseling2005,
author = {Wesseling, Sebastiaan and Ishola, David A., Jr. and Joles, Jaap A.
and Bluyssen, Hans A. and Koomans, Hein A. and Braam, Branko},
title = {Resistance to oxidative stress by chronic infusion of angiotensin
II in mouse kidney is not mediated by the AT2 receptor},
journal = {Am J Physiol Renal Physiol},
year = {2005},
volume = {288},
pages = {F1191--1200},
number = {6},
month = jun,
abstract = {Wild-type mice are resistant to ANG II-induced renal injury and hence
form an attractive model to study renal defense against ANG II. The
present study tested whether ANG II induces expression of antioxidative
genes via the AT2 receptor in renal cortex and thereby counteracts
prooxidative forces. ANG II was infused in female C57BL/6J mice for
28 days and a subgroup received AT2 receptor antagonist (PD-123,319)
for the last 3 days. ANG II induced hypertension and aortic hypertrophy;
proteinuria and renal injury were absent. Urinary nitric oxide metabolites
(NOx) were decreased, and lipid peroxide (TBARS) excretion remained
unchanged. Expression of NADPH oxidase components was decreased in
renal cortex but induced in aorta. Heme oxygenase-1 (HO-1) was induced
in both renal cortex and aorta. In contrast, ANG II suggestively
increased AT2 receptor expression in kidney but not in aorta. AT2
receptor blockade enhanced hypertension in ANG II-infused mice, reversed
ANG II effects on NOx excretion, but did not affect TBARS. Despite
its prohypertensive effect, expression of prooxidative genes in the
renal cortex decreased rather than increased after short-term AT2
receptor blockade and renal HO-1 induction after ANG II was normalized.
Thus chronic ANG II infusion in mice induces hypertension but not
oxidative stress. In contrast to the response in aorta, gene expression
of components of NADPH-oxidase was not enhanced in renal cortex.
Although ANG II administration induced renal cortical AT2 receptor
expression, blockade of that receptor did not unveil the AT2 receptor
as intrarenal dampening factor of prooxidative forces.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/288/6/F1191}
}
@ARTICLE{Wesselkamper2005,
author = {Wesselkamper, Scott C. and Case, Lisa M. and Henning, Lisa N. and
Borchers, Michael T. and Tichelaar, Jay W. and Mason, John M. and
Dragin, Nadine and Medvedovic, Mario and Sartor, Maureen A. and Tomlinson,
Craig R. and Leikauf, George D.},
title = {Gene Expression Changes during the Development of Acute Lung Injury
Role of Transforming Growth Factor {beta}},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2005},
volume = {172},
pages = {1399--1411},
number = {11},
month = dec,
abstract = {Rationale: Acute lung injury can occur from multiple causes, resulting
in high mortality. The pathophysiology of nickel-induced acute lung
injury in mice is remarkably complex, and the molecular mechanisms
are uncertain. Objectives: To integrate molecular pathways and investigate
the role of transforming growth factor {beta} (TGF-{beta}) in acute
lung injury in mice. Methods: cDNA microarray analyses were used
to identify lung gene expression changes after nickel exposure. MAPPFinder
analysis of the microarray data was used to determine significantly
altered molecular pathways. TGF-{beta}1 protein in bronchoalveolar
lavage fluid, as well as the effect of inhibition of TGF-{beta},
was assessed in nickel-exposed mice. The effect of TGF-{beta} on
surfactant-associated protein B (Sftpb) promoter activity was measured
in mouse lung epithelial cells. Measurements and Main Results: Genes
that decreased the most after nickel exposure play important roles
in lung fluid absorption or surfactant and phospholipid synthesis,
and genes that increased the most were involved in TGF-{beta} signaling.
MAPPFinder analysis further established TGF-{beta} signaling to be
significantly altered. TGF-{beta}-inducible genes involved in the
regulation of extracellular matrix function and fibrinolysis were
significantly increased after nickel exposure, and TGF-{beta}1 protein
was also increased in the lavage fluid. Pharmacologic inhibition
of TGF-{beta} attenuated nickel-induced protein in bronchoalveolar
lavage. In addition, treatment with TGF-{beta}1 dose-dependently
repressed Sftpb promoter activity in vitro, and a novel TGF-{beta}-responsive
region in the Sftpb promoter was identified. Conclusions: These data
suggest that TGF-{beta} acts as a central mediator of acute lung
injury through the alteration of several different molecular pathways.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/172/11/1399}
}
@ARTICLE{Wesselkamper2006,
author = {Wesselkamper, Scott C. and McDowell, Susan A. and Medvedovic, Mario
and Dalton, Timothy P. and Deshmukh, Hitesh S. and Sartor, Maureen
A. and Case, Lisa M. and Henning, Lisa N. and Borchers, Michael T.
and Tomlinson, Craig R. and Prows, Daniel R. and Leikauf, George
D.},
title = {The Role of Metallothionein in the Pathogenesis of Acute Lung Injury},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2006},
volume = {34},
pages = {73--82},
number = {1},
month = jan,
abstract = {Often fatal, acute lung injury has a complicated etiology. Previous
studies from our laboratory in mice have demonstrated that survival
during acute lung injury is a complex trait governed by multiple
loci. We also found that the increase in metallothionein (MT) is
one of the greatest noted in transcriptome-wide analyses of gene
expression. To assess the role of MT in nickel-induced acute lung
injury, the survival of Mt-transgenic, Mt1/2(+/+), and Mt1/2(+/+)
mice was compared. Pulmonary inflammation and global gene expression
were compared in Mt1/2(+/+) and Mt1/2(+/+) mice. Gene-targeted Mt1/2(+/+)
mice were more susceptible than Mt1/2(+/+) mice to nickel-induced
inflammation, surfactant-associated protein B transcript loss, and
lethality. Similarly, Mt-transgenic mice exhibited increased survival.
MAPPFinder analyses also noted significant decreases in genes involved
in protein processing (e.g., ubiquitination, folding), which were
greater in Mt1/2(+/+) mice as compared with Mt1/2(+/+) mice early
in the progression of acute lung injury, possibly due to a zinc-mediated
transcript destabilization. In contrast, transcript levels of genes
associated with the inflammatory response, extracellular matrix regulation,
and coagulation/fibrinolysis were increased more in Mt1/2(+/+) mice
as compared with Mt1/2(+/+) mice late in the development of acute
lung injury. Thus, MT ultimately improves survival in the progression
of acute lung injury in mice. Transcriptome-wide analysis suggests
that this survival may be mediated through changes in the destabilization
of transcripts associated with protein processing, the subsequent
augmentation of transcripts controlling inflammation, extracellular
matrix regulation, coagulation/fibrinolysis, and disruption of surfactant
homeostasis.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/34/1/73}
}
@ARTICLE{Wessells2009,
author = {Wessells, Hunter and Sullivan, Chris J. and Tsubota, Yoshiaki and
Engel, Karen L. and Kim, Bryan and Olson, N. Eric and Thorner, Daniel
and Chitaley, Kanchan},
title = {Transcriptional profiling of human cavernosal endothelial cells reveals
distinctive cell adhesion phenotype and role for claudin 11 in vascular
barrier function},
journal = {Physiol Genomics},
year = {2009},
volume = {39},
pages = {100--108},
number = {2},
month = oct,
abstract = {To determine specific molecular features of endothelial cells (ECs)
relevant to the physiological process of penile erection we compared
gene expression of human EC derived from corpus cavernosum of men
with and without erectile dysfunction (HCCEC) to coronary artery
(HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays
and GeneSifter software. Genes differentially expressed across samples
were partitioned around medoids to identify genes with highest expression
in HCCEC. A total of 190 genes/transcripts were highly expressed
only in HCCEC. Gene Ontology classification indicated cavernosal
enrichment in genes related to cell adhesion, extracellular matrix,
pattern specification and organogenesis. Kyoto Encyclopedia of Genes
and Genomes (KEGG) pathway analysis showed high expression of genes
relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine
receptor interaction. Real-time PCR confirmed expression differences
in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican.
CLDN11, a component of tight junctions not previously described in
ECs, was highly expressed only in HCCEC and its knockdown by siRNA
significantly reduced transendothelial electrical resistance in HCCEC.
Overall, cavernosal ECs exhibited a transcriptional profile encoding
matrix and adhesion proteins that regulate structural and functional
characteristics of blood vessels. Contribution of the tight junction
protein CLDN11 to barrier function in endothelial cells is novel
and may reflect hemodynamic requirements of the corpus cavernosum.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/39/2/100}
}
@ARTICLE{West2007,
author = {West, Alina Nico and Neale, Geoffrey A. and Pounds, Stanley and Figueredo,
Bonald C. and Rodriguez Galindo, Carlos and Pianovski, Mara Albonei
D. and Oliveira Filho, Antonio G. and Malkin, David and Lalli, Enzo
and Ribeiro, Raul and Zambetti, Gerard P.},
title = {Gene Expression Profiling of Childhood Adrenocortical Tumors},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {600--608},
number = {2},
month = jan,
abstract = {Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies;
little is known regarding their etiology and biology. To provide
additional insight into the nature of ACT, we determined the gene
expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas,
and one undetermined) and seven normal adrenal glands. Distinct patterns
of gene expression, validated by quantitative real-time PCR and Western
blot analysis, were identified that distinguish normal adrenal cortex
from tumor. Differences in gene expression were also identified between
adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical
carcinomas were found to share similar patterns of gene expression
when compared with those published for adult ACT. This study represents
the first microarray analysis of childhood ACT. Our findings lay
the groundwork for establishing gene expression profiles that may
aid in the diagnosis and prognosis of pediatric ACT, and in the identification
of signaling pathways that contribute to this disease. [Cancer Res
2007;67(2):600-8]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/2/600}
}
@ARTICLE{West2010,
author = {West, F.D. and Roche-Rios, M.I. and Abraham, S. and Rao, R.R. and
Natrajan, M.S. and Bacanamwo, M. and Stice, S.L.},
title = {KIT ligand and bone morphogenetic protein signaling enhances human
embryonic stem cell to germ-like cell differentiation},
journal = {Hum. Reprod.},
year = {2010},
volume = {25},
pages = {168--178},
number = {1},
month = jan,
abstract = {BACKGROUNDSignaling mechanisms involved in early human germ cell development
are largely unknown and believed to be similar to mouse germ cell
development; however, there may be species specific differences.
KIT ligand (KITL) and Bone morphogenetic protein 4 (BMP4) are necessary
in mouse germ cell development and may play an important role in
human germ cell development. METHODSKITL signaling studies were conducted
by differentiating human embryonic stem cells (hESCs) on KITL wild-type,
hetero- or homozygous knockout feeders for 10 days, and the effects
of BMP signaling was determined by differentiation in the presence
of BMP4 or its antagonist, Noggin. The formation of germ-like cells
was ascertained by immunocytochemistry, flow cytometry and quantitative
RT-PCR for germ cell markers. RESULTSThe loss of KITL in enrichment
and differentiation cultures resulted in significant down-regulation
of germ cell genes and a 70.5% decrease in germ-like (DDX4+ POU5F1+)
cells, indicating that KITL is involved in human germ cell development.
Moreover, endogenous BMP signaling caused germ-like (DDX4+ POU5F1+)
cell differentiation, and the inhibition of this pathway caused a
significant decrease in germ cell gene expression and in the number
of DDX4+ POU5F1+ cells. Further, we demonstrated that eliminating
feeders but maintaining their secreted extracellular matrix is sufficient
to sustain the increased numbers of DDX4+ POU5F1+ cells in culture.
However, this resulted in decreased germ cell gene expression. CONCLUSIONSFrom
these studies, we establish that KITL and BMP4 germ cell signaling
affects in vitro formation of hESC derived germ-like cells and we
suggest that they may play an important role in normal human germ
cell development.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/25/1/168}
}
@ARTICLE{West2008,
author = {West, Franklin D. and Machacek, Dave W. and Boyd, Nolan L. and Pandiyan,
Kurinji and Robbins, Kelly R. and Stice, Steven L.},
title = {Enrichment and Differentiation of Human Germ-Like Cells Mediated
by Feeder Cells and Basic Fibroblast Growth Factor Signaling},
journal = {STEM CELLS},
year = {2008},
volume = {26},
pages = {2768--2776},
number = {11},
abstract = {Abstract 10.1634/stemcells.2008-0124.abs Human embryonic stem cells
(hESCs) have recently demonstrated the potential for differentiation
into germ-like cells in vitro. This provides a novel model for understanding
human germ cell development and human infertility. Mouse embryonic
fibroblast (MEF) feeders and basic fibroblast growth factor (bFGF)
are two sources of signaling that are essential for primary culture
of germ cells, yet their role has not been examined in the derivation
of germ-like cells from hESCs. Here protein and gene expression demonstrated
that both MEF feeders and bFGF can significantly enrich germ cell
differentiation from hESCs. Under enriched differentiation conditions,
flow cytometry analysis proved 69% of cells to be positive for DDX4
and POU5F1 protein expression, consistent with the germ cell lineage.
Importantly, removal of bFGF from feeder-free cultures resulted in
a 50% decrease in POU5F1- and DDX4-positive cells. Quantitative reverse
transcription-polymerase chain reaction analysis established that
bFGF signaling resulted in an upregulation of genes involved in germ
cell differentiation with or without feeders; however, feeder conditions
caused significant upregulation of premigratory/migratory (Ifitm3,
DAZL, NANOG, and POU5F1) and postmigratory (PIWIL2, PUM2) genes,
along with the meiotic markers SYCP3 and MLH1. After further differentiation,
>90% of cells expressed the meiotic proteins SYCP3 and MLH1. This
is the first demonstration that signaling from MEF feeders and bFGF
can induce a highly enriched population of germ-like cells derived
from hESCs, thus providing a critically needed model for further
investigation of human germ cell development and signaling. Disclosure
of potential conflicts of interest is found at the end of this article.},
issn = {1549-4918},
keywords = {Embryonic stem cell, Differentiation, In vitro culture, Stem cell
microenvironment},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2008-0124}
}
@ARTICLE{West2008a,
author = {West, Kimberlee A. and Johnson, David R. and Hu, Ping and DeSantis,
Todd Z. and Brodie, Eoin L. and Lee, Patrick K. H. and Feil, Helene
and Andersen, Gary L. and Zinder, Stephen H. and Alvarez-Cohen, Lisa},
title = {Comparative Genomics of "Dehalococcoides ethenogenes" 195 and an
Enrichment Culture Containing Unsequenced "Dehalococcoides" Strains},
journal = {Appl. Envir. Microbiol.},
year = {2008},
volume = {74},
pages = {3533--3540},
number = {11},
month = jun,
abstract = {Tetrachloroethene (PCE) and trichloroethene (TCE) are prevalent groundwater
contaminants that can be completely reductively dehalogenated by
some "Dehalococcoides" organisms. A Dehalococcoides-organism-containing
microbial consortium (referred to as ANAS) with the ability to degrade
TCE to ethene, an innocuous end product, was previously enriched
from contaminated soil. A whole-genome photolithographic microarray
was developed based on the genome of "Dehalococcoides ethenogenes"
195. This microarray contains probes designed to hybridize to >99%
of the predicted protein-coding sequences in the strain 195 genome.
DNA from ANAS was hybridized to the microarray to characterize the
genomic content of the ANAS enrichment. The microarray results revealed
that the genes associated with central metabolism, including an apparently
incomplete carbon fixation pathway, cobalamin-salvaging system, nitrogen
fixation pathway, and five hydrogenase complexes, are present in
both strain 195 and ANAS. Although the gene encoding the TCE reductase,
tceA, was detected, 13 of the 19 reductive dehalogenase genes present
in strain 195 were not detected in ANAS. Additionally, 88% of the
genes in predicted integrated genetic elements in strain 195 were
not detected in ANAS, consistent with these elements being genetically
mobile. Sections of the tryptophan operon and an operon encoding
an ABC transporter in strain 195 were also not detected in ANAS.
These insights into the diversity of Dehalococcoides genomes will
improve our understanding of the physiology and evolution of these
bacteria, which is essential in developing effective strategies for
the bioremediation of PCE and TCE in the environment.},
url = {http://aem.asm.org/cgi/content/abstract/74/11/3533}
}
@ARTICLE{West-Farrell2009,
author = {West-Farrell, Erin R. and Xu, Min and Gomberg, Monica A. and Chow,
Yee Hoong and Woodruff, Teresa K. and Shea, Lonnie D.},
title = {The Mouse Follicle Microenvironment Regulates Antrum Formation and
Steroid Production: Alterations in Gene Expression Profiles},
journal = {Biol Reprod},
year = {2009},
volume = {80},
pages = {432--439},
number = {3},
month = mar,
abstract = {Folliculogenesis is a coordinated process, and the genes that regulate
development are difficult to investigate in vivo. In vitro culture
systems permit the assessment of individual follicles during development,
thereby enabling gene expression patterns to be monitored during
follicle development. Mouse multilayered secondary follicles (150-180
{micro}m in diameter) were cultured in three-dimensional matrices
of varying physical properties for up to 8 days. During this period
of follicle growth in vitro, antrum formation and steroid production
were monitored, and mRNA was isolated. The expression levels of genes
(Star, Cyp11a1, Cyp17a1, Hsd3b1, Cyp19a1, Fshr, Lhcgr, Aqp7, Aqp8,
Aqp9, and Hif1a) were measured and correlated to follicle developmental
status. Follicles that developed an antrum and produced appropriate
levels of estrogen and progesterone had unchanging expression of
Star, Aqp7, Aqp8, and Hif1a and a 34-fold increase in Cyp19a1 expression
at Day 8 of culture and had elevated Lhcgr at Days 6 and 8 of culture.
Follicles that were healthy but did not form an antrum or produce
appropriate levels of steroids, however, demonstrated increasing
levels of Star, Aqp7, Aqp8, and Hif1a and a 15-fold increase in Cyp19a1
at Day 8 of culture, and Lhcgr levels were not elevated until Day
8 of culture. To our knowledge, this study provides the first temporal
analysis of gene expression using individual culture in alginate
hydrogels that correlates growth and steroidogenesis during follicle
development and identifies expression patterns in healthy follicles
and in developmentally disadvantaged follicles.},
url = {http://www.biolreprod.org/cgi/content/abstract/80/3/432}
}
@ARTICLE{Westbury2011,
author = {Westbury, Charlotte and Sahlberg, Kristine and Borresen-Dale, Anne-Lise
and Isacke, Clare and Yarnold, John},
title = {Gene expression profiling of human dermal fibroblasts exposed to
bleomycin sulphate does not differentiate between radiation sensitive
and control patients},
journal = {Radiation Oncology},
year = {2011},
volume = {6},
pages = {42},
number = {1},
abstract = {BACKGROUND:Gene expression profiling of the transcriptional response
of human dermal fibroblasts to in vitro radiation has shown promise
as a predictive test of radiosensitivity. This study tested if treatment
with the radiomimetic drug bleomycin sulphate could be used to differentiate
radiation sensitive patients and controls in patients who had previously
received radiotherapy for early breast cancer.FINDINGS:Eight patients
who developed marked late radiation change assessed by photographic
breast appearance and 8 matched patients without any change were
selected from women entered in a prospective randomised trial of
breast radiotherapy fractionation. Gene expression profiling of primary
skin fibroblasts exposed in vitro to bleomycin sulphate and mock
treated fibroblast controls was performed. 973 genes were up-regulated
and 923 down-reguated in bleomycin sulphate treated compared to mock
treated control fibroblasts. Gene ontology analysis revealed enriched
groups were cellular localisation, apoptosis, cell cycle and DNA
damage response for the deregulated genes. No transcriptional differences
were identified between fibroblasts from radiation sensitive cases
and control patients; subgroup analysis using cases exhibiting severe
radiation sensitivity or with high risk alleles present in TGF beta1
also showed no difference.CONCLUSIONS:The transcriptional response
of human dermal fibroblasts to bleomycin sulphate has been characterised.
No differences between clinically radiation sensitive and control
patients were detected using this approach.},
doi = {10.1186/1748-717X-6-42},
issn = {1748-717X},
pubmedid = {21521514},
url = {http://www.ro-journal.com/content/6/1/42}
}
@ARTICLE{Westbury2009,
author = {Westbury, Charlotte B and Reis-Filho, Jorge S and Dexter, Tim and
Mahler-Araujo, Betania and Fenwick, Kerry and Iravani, Marjan and
Grigoriadis, Anita and Parry, Suzanne and Robertson, David and Mackay,
Alan and Ashworth, Alan and Yarnold, John R and Isacke, Clare M},
title = {Genome-wide transcriptomic profiling of microdissected human breast
tissue reveals differential expression of KIT (c-Kit, CD117) and
oestrogen receptor-α (ERα) in response to therapeutic radiation},
journal = {J. Pathol.},
year = {2009},
volume = {219},
pages = {131--140},
number = {1},
abstract = {Abstract 10.1002/path.2581.abs The pathogenesis of late normal tissue
fibrosis after high-dose ionizing radiation involves multiple cell
types and signalling pathways but is not well understood. To identify
the molecular changes occurring after radiotherapy, paired normal
tissue samples were collected from the non-irradiated breast and
from the treated breast of women who had undergone curative radiotherapy
for early breast cancer months or years previously. As radiation
may induce distinct transcriptional changes in the different components
of the breast, laser capture microdissection and gene expression
microarray profiling were performed separately for epithelial and
stromal components and selected genes were validated using immunohistochemistry.
In the epithelial compartment, a reduction of KIT (c-Kit; CD117)
and a reciprocal increase in ESR1 (oestrogen receptor-α, ERα) mRNA
and protein levels were seen in irradiated compared to non-irradiated
samples. In the stromal compartment, extracellular matrix genes including
FN1 (fibronectin 1) and CTGF (connective tissue growth factor; CCN2)
were increased. Further investigation revealed that c-Kit and ERα
were expressed in distinct subpopulations of luminal epithelial cells.
Interlobular c-Kit-positive mast cells were also increased in irradiated
cases not showing features of post-radiation atrophy. Pathway analysis
revealed ‘cancer, reproductive system disease and tumour morphology’
as the most significantly enriched network in the epithelial compartment,
whereas in the stromal component, a significant enrichment for ‘connective
tissue disorders, dermatological diseases and conditions, genetic
disorder’ and ‘cancer, tumour morphology, infection mechanism’
networks was observed. These data identify previously unreported
changes in the epithelial compartment and show altered expression
of genes implicated in late normal tissue injury in the stromal compartment
of normal breast tissue. The findings are relevant to both fibrosis
and atrophy occurring after radiotherapy for early breast cancer.
Copyright © 2009 Pathological Society of Great Britain and Ireland.
Published by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {breast, radiation fibrosis, c-Kit, oestrogen receptor, mast cell,
stem cell factor, laser capture microdissection, gene expression
microarray, pathway analysis},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2581}
}
@ARTICLE{WESTENDORF2006,
author = {WESTENDORF, ASTRID M. and BRUDER, DUNJA and HANSEN, WIEBKE and BUER,
JAN},
title = {Intestinal Epithelial Antigen Induces CD4+ T Cells with Regulatory
Phenotype in a Transgenic Autoimmune Mouse Model},
journal = {Annals of the New York Academy of Sciences},
year = {2006},
volume = {1072},
pages = {401--406},
number = {1},
abstract = {Abstract: Regulatory T cells play a crucial role in the control
of immune responses in the intestinal mucosa and their absence may
predispose to inflammatory bowel disease (IBD). However, the induction
of regulatory T cells at sites of mucosal inflammation is not yet
fully understood and may involve antigen presentation by local immature
dendritic cells and/or intestinal epithelial cells (IECs). VILLIN-HA
mice, which express the hemagglutinin (HA) from influenza virus A
exclusively in enterocytes of the intestinal epithelium, were matched
with T cell receptor (TCR)-HA mice expressing an αβ-TCR which recognizes
a major histocompatibility complex (MHC) class II-restricted epitope
of HA in order to determine the impact of antigen presentation by
IECs on CD4+ T cell immunity. In VILLIN-HA × TCR-HA mice, peripheral
HA-specific lymphocytes showed an activated phenotype and increased
infiltration into the intestinal mucosa without destruction of the
intestinal epithelium. Mucosal lymphocytes from VILLIN-HA × TCR-HA
mice secreted lower amounts of interferon-γ (IFN-γ) and interleukin-2
(IL-2) and exhibited an increased expression of interleukin-10 (IL-10),
Nrp-1, and Foxp3, molecules published as markers for regulatory T
cells. IECs can take up and process antigen but the antigen presentation
capacity of these cells is often inefficient. Functional and molecular
characterization of IECs from VILLIN-HA and VILLIN-HA × TCR-HA transgenic
mice revealed a direct role in the induction of CD4+ T cells with
a regulatory phenotype that maintain intestinal homeostasis.},
issn = {1749-6632},
keywords = {intestinal immunity, transgenic mouse model, regulatory T cells, intestinal
epithelial cells},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1196/annals.1326.035}
}
@ARTICLE{Westendorf2005,
author = {Westendorf, A M and Templin, M and Geffers, R and Deppenmeier, S
and Gruber, A D and Probst-Kepper, M and Hansen, W and Liblau, R
S and Gunzer, F and Bruder, D and Buer, J},
title = {CD4+ T cell mediated intestinal immunity: chronic inflammation versus
immune regulation},
journal = {Gut},
year = {2005},
volume = {54},
pages = {60--69},
number = {1},
month = jan,
abstract = {Background: Several studies have suggested that chronic inflammatory
bowel disease may be a consequence of antigen specific recognition
by appropriate T cells which expand and induce immunopathology. Aims:
We wished to investigate whether autoreactive CD4+ T cells can initiate
the disease on recognition of enterocyte specific antigens directly
and if induction of mucosal tolerance occurs. Methods: Transgenic
mice (VILLIN-HA) were generated that showed specific expression of
haemagglutinin from influenza virus A exclusively in enterocytes
of the intestinal epithelium. To investigate the impact of enterocyte
specific haemagglutinin expression in an autoimmune environment,
we mated VILLIN-HA mice with T cell receptor (TCR)-HA mice expressing
an {alpha}/{beta}-TCR, which recognises an MHC class II restricted
epitope of haemagglutinin, and analysed the HA specific T cells for
induction of autoimmunity or tolerance. Results: In VILLIN-HAxTCR-HA
mice, incomplete central deletion of HA specific lymphocytes occurred.
Peripheral HA specific lymphocytes showed an activated phenotype
and increased infiltration into the intestinal mucosa, but not into
other organs of double transgenic mice. Enterocyte specific lamina
propria lymphocytes showed a dose dependent proliferative response
on antigen stimulation whereas the proliferative capacity of intraepithelial
lymphocytes was reduced. Mucosal lymphocytes from VILLIN-HAxTCR-HA
mice secreted lower amounts of interferon {gamma} and interleukin
(IL)-2 but higher levels of tumour necrosis factor {alpha}, monocyte
chemoattractant protein 1, and IL-6. Mucosal immune reactions were
accompanied by broad changes in the gene expression profile with
expression of proinflammatory genes, but strikingly also a remarkable
set of genes discussed in the context of peripheral induction of
regulatory T cells, including IL-10, Nrp-1, and Foxp3. Conclusions:
Enterocyte specific antigen expression is sufficient to trigger a
specific CD4+ T cell response leading to mucosal infiltration. In
our model, progression to overt clinical disease was counteracted
most likely by induction of regulatory T cells.},
url = {http://gut.bmj.com/cgi/content/abstract/54/1/60}
}
@ARTICLE{Westenfeld2009,
author = {Westenfeld, Ralf and Schafer, Cora and Kruger, Thilo and Haarmann,
Christian and Schurgers, Leon J. and Reutelingsperger, Chris and
Ivanovski, Ognen and Drueke, Tilman and Massy, Ziad A. and Ketteler,
Markus and Floege, Jurgen and Jahnen-Dechent, Willi},
title = {Fetuin-A Protects against Atherosclerotic Calcification in CKD},
journal = {J. Am. Soc. Nephrol.},
year = {2009},
volume = {20},
pages = {1264--1274},
number = {6},
month = jun,
abstract = {Reduced serum levels of the calcification inhibitor fetuin-A associate
with increased cardiovascular mortality in dialysis patients. Fetuin-A-deficient
mice display calcification of various tissues but notably not of
the vasculature. This absence of vascular calcification may result
from the protection of an intact endothelium, which becomes severely
compromised in the setting of atherosclerosis. To test this hypothesis,
we generated fetuin-A/apolipoprotein E (ApoE)-deficient mice and
compared them with ApoE-deficient and wild-type mice with regard
to atheroma formation and extraosseous calcification. We assigned
mice to three treatment groups for 9 wk: (1) Standard diet, (2) high-phosphate
diet, or (3) unilateral nephrectomy (causing chronic kidney disease
[CKD]) plus high-phosphate diet. Serum urea, phosphate, and parathyroid
hormone levels were similar in all genotypes after the interventions.
Fetuin-A deficiency did not affect the extent of aortic lipid deposition,
neointima formation, and coronary sclerosis observed with ApoE deficiency,
but the combination of fetuin-A deficiency, hyperphosphatemia, and
CKD led to a 15-fold increase in vascular calcification in this model
of atherosclerosis. Fetuin-A deficiency almost exclusively promoted
intimal rather than medial calcification of atheromatous lesions.
High-phosphate diet and CKD also led to an increase in valvular calcification
and aorta-associated apoptosis, with wild-type mice having the least,
ApoE-deficient mice intermediate, and fetuin-A/ApoE-deficient mice
the most. In addition, the combination of fetuin-A deficiency, high-phosphate
diet, and CKD in ApoE-deficient mice greatly enhanced myocardial
calcification, whereas the absence of fetuin-A did not affect the
incidence of renal calcification. In conclusion, fetuin-A inhibits
pathologic calcification in both the soft tissue and vasculature,
even in the setting of atherosclerosis.},
url = {http://jasn.asnjournals.org/cgi/content/abstract/20/6/1264}
}
@ARTICLE{Westenfeld2007,
author = {Westenfeld, Ralf and Schafer, Cora and Smeets, Ralf and Brandenburg,
Vincent M. and Floege, Jurgen and Ketteler, Markus and Jahnen-Dechent,
Willi},
title = {Fetuin-A (AHSG) prevents extraosseous calcification induced by uraemia
and phosphate challenge in mice},
journal = {Nephrol. Dial. Transplant.},
year = {2007},
volume = {22},
pages = {1537--1546},
number = {6},
month = jun,
abstract = {Background. Chronic kidney disease (CKD) is associated with vascular
and tissue calcification. The extent of vascular calcification has
been identified as an independent risk factor of cardiovascular death
in patients on haemodialysis. Methods. We studied the role of fetuin-A
in CKD-associated calcification using a mouse model of graded renal
insufficiency generated by nephrectomy and high phosphate diet. We
used wild-type and fetuin-A-deficient mice on the calcification resistant
genetic background C57BL/6 to study the influence on calcification
of CKD, dietary phosphate and fetuin deficiency. Hyperphosphataemia,
elevated BUN, hyperparathyroidism and von Kossa histochemistry served
as indicators of calcification disease. The expression of osteopontin,
a marker of osteoblast-like cell differentiation was analyzed by
realtime PCR and immunohistechemistry. Results. We detected tissue
and genotype-specific susceptibility for calcification. Fetuin-A-deficient
mice with CKD and high phosphate diet had only a moderately elevated
serum calcium phosphate product (6.9 {+/-} 1.4 mmol2/l2), but suffered
severe calcification of kidney, heart and lung. In contrast, wild-type
mice under the same conditions developed renal calcinosis only despite
an elevated serum calcium phosphate product (9.6 {+/-} 0.9 mmol2/l2).
Calcification was preceded by the local induction of osteopontin,
a marker for osteoblast-like cell differentiation. Conclusion. Fetuin-A
deficiency, CKD and high phosphate diet act synergistically in the
pathogenesis of extraosseous calcification.},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/22/6/1537}
}
@ARTICLE{Westenfeld2011,
author = {Westenfeld, Ralf and Schlieper, Georg and Woltje, Michael and Gawlik,
Alexander and Brandenburg, Vincent and Rutkowski, Przemyslaw and
Floege, Jurgen and Jahnen-Dechent, Willi and Ketteler, Markus},
title = {Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications
for post-transplantation bone disease},
journal = {Nephrol. Dial. Transplant.},
year = {2011},
volume = {26},
pages = {4115-4123},
number = {12},
abstract = {Background. Post-transplantation bone disease is associated with a
high degree of morbidity including pain and fractures. Glucocorticoid-induced
osteoporosis on top of pre-existing renal osteodystrophy is considered
the major pathogenic factor, while the role of non-glucocorticoid
immunosuppressants is less well defined. Methods. In this study,
we investigated the influence of sirolimus (SRL) versus calcineurin
inhibitor (CI)-based immunosuppressive regimens on biomarkers of
bone resorption in renal transplant patients. In addition, the impact
of SRL, tacrolimus and mycophenolate mofetil (MMF) on osteoclast
activation and function was assessed in cell culture systems. Results.
Using this approach, we demonstrated reduced serum levels of bone
resorption markers in patients treated with SRL after kidney transplantation
compared to a CI-based regimen. In line with this observation, we
detected profoundly reduced osteoclast differentiation and subsequently
diminished hydroxyapatite resorption in the presence of SRL compared
to MMF and tacrolimus in vitro. Moreover, SRL significantly reduced
osteoclast precursor proliferation in vitro compared to tacrolimus
and led to augmented apoptosis in osteoclast precursors. Conclusions.
Taken together, SRL was shown to inhibit osteoclast formation in
vivo and in vitro. SRL thus may have the potential to balance osteoclast
promoting effects of glucocorticoids and CI, thereby counteracting
the development of accelerated osteoporosis in renal transplant recipients.},
doi = {10.1093/ndt/gfr214},
eprint = {http://ndt.oxfordjournals.org/cgi/reprint/26/12/4115.pdf},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/26/12/4115}
}
@ARTICLE{Western2008,
author = {Western, Patrick S. and Miles, Denise C. and van den Bergen, Jocelyn
A. and Burton, Matt and Sinclair, Andrew H.},
title = {Dynamic Regulation of Mitotic Arrest in Fetal Male Germ Cells},
journal = {STEM CELLS},
year = {2008},
volume = {26},
pages = {339--347},
number = {2},
abstract = {Abstract 10.1634/stemcells.2007-0622.abs During fetal mouse development,
germ cells enter the developing gonad at embryonic day (E) 10–11.
In response to signaling from the male or female gonad, the germ
cells commit either to spermatogenesis at E12.5 and enter mitotic
arrest or to oogenesis and enter meiotic arrest at E13.5. It is unclear
whether male commitment of the germ line and mitotic arrest are directly
associated or whether they are developmentally separate. In addition,
the published data describing the timing of mitotic arrest are inconsistent,
and the molecular processes underlying the control of the cell cycle
during mitotic arrest also remain unknown. Using flow cytometric
techniques, 5-bromo-2′-deoxyuridine labeling, and immunofluorescent
analysis of cell proliferation, we have determined that germ cells
in the embryonic mouse testis arrest in G0 during E12.5 and E14.5.
This process is gradual and occurs in an unsynchronized manner. We
have also purified germ cells and analyzed molecular changes in male
germ cells as they exit the cell cycle. This has allowed us to identify
a series of molecular events, including activation of p27Kip1, p15INK4b,
and p16INK4a; the dephosphorylation and degradation of retinoblastoma
protein; and the suppression of CyclinE, which lead to mitotic arrest.
For the first time, the data presented here accurately define the
mitotic arrest of male germ cells by directly combining the analysis
of cell cycle changes with the examination of functionally defined
cell cycle regulators. Disclosure of potential conflicts of interest
is found at the end of this article.},
issn = {1549-4918},
keywords = {Fetal, Germ cells, Cell cycle, Mitotic arrest, Retinoblastoma, p27Kip1},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1634/stemcells.2007-0622}
}
@ARTICLE{Weston2009,
author = {Weston, Anna and Caminada, Daniel and Galicia, Hector and Fent, Karl},
title = {Effects of lipid-lowering pharmaceuticals bezafibrate and clofibric
acid on lipid metabolism in fathead minnow (Pimephales promelas)},
journal = {Environmental Toxicology and Chemistry},
year = {2009},
volume = {28},
pages = {2648--2655},
number = {12},
abstract = {Abstract The lipid-lowering agents bezafibrate and clofibric acid,
which occur at concentrations up to 3.1 and 1.6 μL, respectively,
are among the most frequently found human pharmaceuticals in the
aquatic environment. In contrast to knowledge about their environmental
occurrence, little is known about their effects in the environment.
The aim of the present study was to analyze effects of these lipid-lowering
agents in fish by focusing on their modes of action, lipid metabolism.
Fathead minnows were exposed in aquaria to measured concentrations
of 0.1, 1.27, 10.18, 101.56, and 106.7 mg/L bezafibrate and to 1.07,
10.75, and 108.91 mg/L clofibric acid for 14 and 21 d, respectively.
After exposure, fish liver was analyzed for expression of peroxisome
proliferator-activated receptor α (PPARα) by quantitative polymerase
chain reaction (PCR), and the PPAR-regulated enzyme fatty acyl-coenzyme-A
oxidase (FAO) involved in fatty acid oxidation. Bezafibrate had no
effect, either on PPARα expression or on FAO activity, at all concentrations.
In contrast, clofibric acid induced FAO activity in male fathead
minnows at 108.91 mg/L. No increase in expression of PPARα messenger
ribonucleic acid was observed. Egg production was apparently decreased
after 21 d of exposure to 108.91 mg/L clofibric acid. The present
study demonstrates that bezafibrate has very little or no effect
on PPARα expression and FAO activity, but clofibric acid affects
FAO activity.},
issn = {1552-8618},
keywords = {Bezafibrate, Clofibric acid, Dibutyl phthalate, Fathead minnows, Pharmaceuticals},
publisher = {Wiley Periodicals, Inc.},
url = {http://dx.doi.org/10.1897/09-087.1}
}
@ARTICLE{Weston2011,
author = {Weston, Michael D. and Pierce, Marsha L. and Jensen-Smith, Heather
C. and Fritzsch, Bernd and Rocha-Sanchez, Sonia and Beisel, Kirk
W. and Soukup, Garrett A.},
title = {MicroRNA-183 family expression in hair cell development and requirement
of microRNAs for hair cell maintenance and survival},
journal = {Developmental Dynamics},
year = {2011},
volume = {240},
pages = {808--819},
number = {4},
abstract = {Abstract MicroRNAs (miRNAs) post-transcriptionally repress complementary
target gene expression and can contribute to cell differentiation.
The coordinate expression of miRNA-183 family members (miR-183, miR-96,
and miR-182) has been demonstrated in sensory cells of the mouse
inner ear and other vertebrate sensory organs. To further examine
hair cell miRNA expression in the mouse inner ear, we have analyzed
miR-183 family expression in wild type animals and various mutants
with defects in neurosensory development. miR-183 family member expression
follows neurosensory cell specification, exhibits longitudinal (basal-apical)
gradients in maturating cochlear hair cells, and is maintained in
sensory neurons and most hair cells into adulthood. Depletion of
hair cell miRNAs resulting from Dicer1 conditional knockout (CKO)
in Atoh1-Cre transgenic mice leads to more disparate basal-apical
gene expression profiles and eventual hair cell loss. Results suggest
that hair cell miRNAs subdue cochlear gradient gene expression and
are required for hair cell maintenance and survival. Developmental
Dynamics 240:808–819, 2011. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/dvdy.22591},
issn = {1097-0177},
keywords = {microRNA, Dicer, conditional knockout, inner ear, cochlea, sensory
epithelium, hair cells, sensory neurons, development, maturation,
maintenance},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.22591}
}
@ARTICLE{Weston2006,
author = {Weston, Michael D. and Pierce, Marsha L. and Rocha-Sanchez, Sonia
and Beisel, Kirk W. and Soukup, Garrett A.},
title = {MicroRNA gene expression in the mouse inner ear},
journal = {Brain Research},
year = {2006},
volume = {1111},
pages = {95--104},
number = {1},
month = sep,
abstract = {MicroRNAs (miRNAs) are small non-coding RNAs that function through
the RNA interference (RNAi) pathway and post-transcriptionally regulate
gene expression in eukaryotic organisms. While miRNAs are known to
affect cellular proliferation, differentiation, and morphological
development, neither their expression nor roles in mammalian inner
ear development have been characterized. We have investigated the
extent of miRNA expression at various time points throughout maturation
of the postnatal mouse inner ear by microarray analysis. Approximately
one third of known miRNAs are detected in the inner ear, and their
expression persists to adulthood. Expression of such miRNAs is validated
by quantitative PCR and northern blot analysis. Further analysis
by in situ hybridization demonstrates that certain miRNAs exhibit
cell-specific expression patterns in the mouse inner ear. Notably,
we demonstrate that miRNAs previously associated with mechanosensory
cells in zebrafish are also expressed in hair cells of the auditory
and vestibular endorgans. Our results demonstrate that miRNA expression
is abundant in the mammalian inner ear and that certain miRNAs are
evolutionarily associated with mechanosensory cell development and/or
function. The data suggest that miRNAs contribute substantially to
genetic programs intrinsic to development and function of the mammalian
inner ear and that specific miRNAs might influence formation of sensory
epithelia from the primitive otic neuroepithelium.},
issn = {0006-8993},
keywords = {Cochlea, Hair cell, Inner ear, MicroRNA, RNA interference},
url = {http://www.sciencedirect.com/science/article/B6SYR-4KM46XY-6/2/7700c017e530b63d4758e26abe9c2435}
}
@ARTICLE{Westwell-Roper2011,
author = {Westwell-Roper, Clara and Dai, Derek L. and Soukhatcheva, Galina
and Potter, Kathryn J. and van Rooijen, Nico and Ehses, Jan A. and
Verchere, C. Bruce},
title = {IL-1 Blockade Attenuates Islet Amyloid Polypeptide-Induced Proinflammatory
Cytokine Release and Pancreatic Islet Graft Dysfunction},
journal = {J. Immunol.},
year = {2011},
volume = {187},
pages = {2755-2765},
number = {5},
abstract = {Islets from patients with type 2 diabetes exhibit {beta} cell dysfunction,
amyloid deposition, macrophage infiltration, and increased expression
of proinflammatory cytokines and chemokines. We sought to determine
whether human islet amyloid polypeptide (hIAPP), the main component
of islet amyloid, might contribute to islet inflammation by recruiting
and activating macrophages. Early aggregates of hIAPP, but not nonamyloidogenic
rodent islet amyloid polypeptide, caused release of CCL2 and CXCL1
by islets and induced secretion of TNF-, IL-1, IL-1{beta}, CCL2,
CCL3, CXCL1, CXCL2, and CXCL10 by C57BL/6 bone marrow-derived macrophages.
hIAPP-induced TNF- secretion was markedly diminished in MyD88-, but
not TLR2- or TLR4-deficient macrophages, and in cells treated with
the IL-1R antagonist (IL-1Ra) anakinra. To determine the significance
of IL-1 signaling in hIAPP-induced pancreatic islet dysfunction,
islets from wild-type or hIAPP-expressing transgenic mice were transplanted
into diabetic NOD/SCID recipients implanted with mini-osmotic pumps
containing IL-1Ra (50 mg/kg/d) or saline. IL-1Ra significantly improved
the impairment in glucose tolerance observed in recipients of transgenic
grafts 8 wk following transplantation. Islet grafts expressing hIAPP
contained amyloid deposits in close association with F4/80-expressing
macrophages. Transgenic grafts contained 50% more macrophages than
wild-type grafts, an effect that was inhibited by IL-1Ra. Our results
suggest that hIAPP-induced islet chemokine secretion promotes macrophage
recruitment and that IL-1R/MyD88, but not TLR2 or TLR4 signaling
is required for maximal macrophage responsiveness to prefibrillar
hIAPP. These data raise the possibility that islet amyloid-induced
inflammation contributes to {beta} cell dysfunction in type 2 diabetes
and islet transplantation.},
doi = {10.4049/jimmunol.1002854},
eprint = {http://www.jimmunol.org/cgi/reprint/187/5/2755.pdf},
url = {http://www.jimmunol.org/cgi/content/abstract/187/5/2755}
}
@ARTICLE{Weterman2012,
author = {Weterman, Marian A.J. and Sorrentino, Vincenzo and Kasher, Paul R.
and Jakobs, Marja E. and van Engelen, Baziel G.M. and Fluiter, Kees
and de Wissel, Marit B. and Sizarov, Aleksander and Nurnberg, Gudrun
and Nurnberg, Peter and Zelcer, Noam and Schelhaas, H. Jurgen and
Baas, Frank},
title = {A frameshift mutation in LRSAM1 is responsible for a dominant hereditary
polyneuropathy},
journal = {Hum. Mol. Genet.},
year = {2012},
volume = {21},
pages = {358-370},
number = {2},
abstract = {Despite the high number of genes identified in hereditary polyneuropathies/Charcot-Marie-Tooth
(CMT) disease, the genetic defect in many families is still unknown.
Here we report the identification of a new gene for autosomal dominant
axonal neuropathy in a large three-generation family. Linkage analysis
identified a 5 Mb region on 9q33-34 with a LOD score of 5.12. Sequence
capture and next-generation sequencing of the region of interest
identified five previously unreported non-synonymous heterozygous
single nucleotide changes or indels, four of which were confirmed
by Sanger sequencing. Two sequence variants co-segregated with the
disease, and one, a 2 bp insertion in the last exon of LRSAM1, was
also absent in 676 ethnicity-matched control chromosomes. This frameshift
mutation (p.Leu708Argfx28) is located in the C-terminal RING finger
motif of the encoded protein. Ubiquitin ligase activity in transfected
cells with constructs carrying the patient mutation was affected
as measured by a higher level of abundance of TSG101, the only reported
target of LRSAM1. Injections of morpholino oligonucleotides in zebrafish
embryos directed against the ATG or last splice site of zebrafish
Lrsam1 disturbed neurodevelopment, showing a less organized neural
structure and, in addition, affected tail formation and movement.
LRSAM1 is highly expressed in adult spinal cord motoneurons as well
as in fetal spinal cord and muscle tissue. Recently, a homozygous
mutation in LRSAM1 was proposed as a strong candidate for the disease
in a family with recessive axonal polyneuropathy. Our data strongly
support the hypothesis that LRSAM1 mutations can cause both dominant
and recessive forms of CMT.},
doi = {10.1093/hmg/ddr471},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/21/2/358.pdf},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/21/2/358}
}
@ARTICLE{Whale2006,
author = {Whale, Tyler A. and Wilson, Heather L. and Tikoo, Suresh K. and Babiuk,
Lorne A. and Griebel, Philip J.},
title = {Passively acquired membrane proteins alter the functional capacity
of bovine polymorphonuclear cells},
journal = {J. Leukoc. Biol.},
year = {2006},
volume = {80},
pages = {481--491},
number = {3},
month = sep,
abstract = {We have previously shown that bovine polymorphonuclear cells (PMNs)
have an impressive capacity to passively acquire membrane lipids
and proteins from apoptotic cells. The present study used confocal
microscopy to analyze the interaction between PMNs and a variety
of donor cells, and assays were used to determine if passively acquired
membrane proteins altered PMN biology. Confocal microscopy revealed
that direct cell-cell contact and microparticles shed by donor cells
may be a source of passively acquired membranes and integral membrane
proteins, which then integrate into the PMN plasma membrane. Donor
cells expressing green fluorescent protein in their cytoplasm were
also used to demonstrate the transfer of cytoplasmic proteins from
donor cells to PMNs. The functional consequences of passive membrane
protein acquisition by PMNs were then investigated using two distinct
systems. First, PMNs were incubated with membranes isolated from
an adenovirus-permissive cell line, and this passive transfer of
cell membranes significantly increased adenovirus infection of PMNs.
Second, major histocompatibility complex (MHC) class II molecules
were passively transferred from ovine B cells to bovine PMNs, and
PMNs with ovine MHC class II on their surface were able to induce
a proliferative response and increased cytokine gene expression in
alloreactive bovine T cell lines. In conclusion, passively acquired
membrane proteins integrated into the plasma membrane of bovine PMNs
and altered the functional capacity of these cells.},
url = {http://www.jleukbio.org/cgi/content/abstract/80/3/481}
}
@ARTICLE{Whaley-Connell2006,
author = {Whaley-Connell, Adam T. and Chowdhury, Nazif A. and Hayden, Melvin
R. and Stump, Craig S. and Habibi, Javad and Wiedmeyer, Charles E.
and Gallagher, Patricia E. and Ann Tallant, E. and Cooper, Shawna
A. and Link, C. Daniel and Ferrario, Carlos and Sowers, James R.},
title = {Oxidative stress and glomerular filtration barrier injury: role of
the renin-angiotensin system in the Ren2 transgenic rat},
journal = {Am J Physiol Renal Physiol},
year = {2006},
volume = {291},
pages = {F1308--1314},
number = {6},
month = dec,
abstract = {TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene,
manifest hypertension, and exhibit increased tissue ANG II levels
and oxidative stress. Evidence indicates that elevated tissue ANG
II contributes to oxidative stress, increases in glomerular macromolecular
permeability, and consequent albuminuria. Furthermore, angiotensin
type 1 receptor (AT1R) blockers reduce albuminuria and slow progression
of renal disease. However, it is not known whether improvements in
glomerular filtration barrier integrity and albuminuria during treatment
are related to reductions in oxidative stress and/or kidney renin-angiotensin
system (RAS) activity. To investigate the renal protective effects
of AT1R blockade, we treated young (6-7 wk old) male Ren2 rats with
valsartan (Ren2-V; 30 mg/kg) for 3 wk and measured urine albumin,
kidney malondialdehyde (MDA), RAS component mRNAs, and NADPH oxidase
subunits (gp91phox and Rac1) compared with age-matched untreated
Ren2 and Sprague-Dawley (S-D) rats. Basement membrane thickness,
slit pore diameter and number, and foot process base width were measured
by transmission electron microscopy (TEM). Results indicate that
AT1R blockade lowered systolic blood pressure (30%), albuminuria
(91%), and kidney MDA (80%) in Ren2-V compared with untreated Ren2
rats. Increased slit pore number and diameter and reductions in basement
membrane thickness and podocyte foot process base width were strongly
associated with albuminuria and significantly improved following
AT1R blockade. AT1R blockade was also associated with increased angiotensin-converting
enzyme-2 and neprilysin expression, demonstrating a beneficial shift
in balance of renal RAS. Thus reductions in blood pressure, albuminuria,
and tissue oxidative stress with AT1R blockade were associated with
improved indexes of glomerular filtration barrier integrity and renal
RAS in Ren2 rats.},
url = {http://ajprenal.physiology.org/cgi/content/abstract/291/6/F1308}
}
@ARTICLE{Whalley2011,
author = {Whalley, Helen J. and Sargeant, Alexander W. and Steele, John F.C.
and Lacoere, Tim and Lamb, Rebecca and Saunders, Nigel J. and Knight,
Heather and Knight, Marc R.},
title = {Transcriptomic Analysis Reveals Calcium Regulation of Specific Promoter
Motifs in Arabidopsis},
journal = {PLANT CELL},
year = {2011},
volume = {23},
pages = {4079-4095},
number = {11},
abstract = {Increases in intracellular calcium concentration ([Ca2+]c) mediate
plant responses to stress by regulating the expression of genes encoding
proteins that confer tolerance. Several plant stress genes have previously
been shown to be calcium-regulated, and in one case, a specific promoter
motif Abscisic Acid Responsive-Element (ABRE) has been found to be
regulated by calcium. A comprehensive survey of the Arabidopsis thaliana
transcriptome for calcium-regulated promoter motifs was performed
by measuring the expression of genes in Arabidopsis seedlings responding
to three calcium elevations of different characteristics, using full
genome microarray analysis. This work revealed a total of 269 genes
upregulated by [Ca2+]c in Arabidopsis. Bioinformatic analysis strongly
indicated that at least four promoter motifs were [Ca2+]c-regulated
in planta. We confirmed this finding by expressing in plants chimeric
gene constructs controlled exclusively by these cis-elements and
by testing the necessity and sufficiency of calcium for their expression.
Our data reveal that the C-Repeat/Drought-Responsive Element, Site
II, and CAM box (along with the previously identified ABRE) promoter
motifs are calcium-regulated. The identification of these promoter
elements targeted by the second messenger intracellular calcium has
implications for plant signaling in response to a variety of stimuli,
including cold, drought, and biotic stress.},
doi = {10.1105/tpc.111.090480},
eprint = {http://www.plantcell.org/cgi/reprint/23/11/4079.pdf},
url = {http://www.plantcell.org/cgi/content/abstract/23/11/4079}
}
@ARTICLE{WHEAT2011,
author = {WHEAT, CHRISTOPHER W. and FESCEMYER, HOWARD W. and KVIST, J. and
TAS, EVA and VERA, J. CRISTOBAL and FRILANDER, MIKKO J. and HANSKI,
ILKKA and MARDEN, JAMES H.},
title = {Functional genomics of life history variation in a butterfly metapopulation},
journal = {Molecular Ecology},
year = {2011},
volume = {20},
pages = {1813--1828},
number = {9},
abstract = {Abstract In fragmented landscapes, small populations frequently go
extinct and new ones are established with poorly understood consequences
for genetic diversity and evolution of life history traits. Here,
we apply functional genomic tools to an ecological model system,
the well-studied metapopulation of the Glanville fritillary butterfly.
We investigate how dispersal and colonization select upon existing
genetic variation affecting life history traits by comparing common-garden
reared 2-day adult females from new populations with those from established
older populations. New-population females had higher expression of
abdomen genes involved in egg provisioning and thorax genes involved
in the maintenance of flight muscle proteins. Physiological studies
confirmed that new-population butterflies have accelerated egg maturation,
apparently regulated by higher juvenile hormone titer and angiotensin
converting enzyme mRNA, as well as enhanced flight metabolism. Gene
expression varied between allelic forms of two metabolic genes (Pgi
and Sdhd), which themselves were associated with differences in flight
metabolic rate, population age and population growth rate. These
results identify likely molecular mechanisms underpinning life history
variation that is maintained by extinction–colonization dynamics
in metapopulations.},
doi = {10.1111/j.1365-294X.2011.05062.x},
issn = {1365-294X},
keywords = {ecological genomics, gene expression, Glanville fritillary, microarray,
mixed model analysis, physiological ecology, polymorphism, reproduction},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2011.05062.x}
}
@ARTICLE{Whelehan2011,
author = {Whelehan, Cormac J. and Meade, Kieran G. and Eckersall, P. David
and Young, Fiona J. and O'Farrelly, Cliona},
title = {Experimental Staphylococcus aureus infection of the mammary gland
induces region-specific changes in innate immune gene expression},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {140},
pages = {181--189},
number = {3-4},
month = apr,
abstract = {Staphylococcus aureus is a prolific mastitis-causing bacterium that
resides naturally in the environment of the dairy cow. The aim of
this study was to profile immune gene expression in tissue from the
alveolar, ductal, gland cistern and teat canal regions of the bovine
mammary gland following intramammary infection with S. aureus. Quantitative
real-time PCR (qPCR) was used to profile expression of innate immune
genes including pattern recognition receptors (PRRs), cytokines,
antimicrobial peptides (AMPs) and acute phase proteins (APPs). Consistent
expression of Toll-like receptors (TLRs) 1-10 and NOD-like receptors
(NODs) 1-2 was detected in all four tissue regions. Pro-inflammatory
cytokines (IL6, IL17A and IL8) and anti-inflammatory cytokine (IL10)
were induced in all 4 tissues. APP (SAA3 and HP) and AMP (DEFB4 and
DEFB5) genes showed the greatest induction throughout the mammary
gland in response to S. aureus, with particularly high expression
in alveolar tissue (SAA3 and HP >133- and >80-fold respectively,
P < 0.05; DEFB4 and DEFB5 >9- and >27-fold respectively, P < 0.05).
Collectively, our data show both sentinel and effector immune functions
throughout the mammary gland in response to S. aureus challenge.},
issn = {0165-2427},
keywords = {Dairy cow, Mastitis, Staphylococcus aureus, qPCR, Pattern recognition
receptor, Acute phase protein, [beta]-defensin},
url = {http://www.sciencedirect.com/science/article/pii/S0165242710003971}
}
@ARTICLE{Whistler2010,
author = {Whistler, Toni and Chiang, Cheng-Feng and Lonergan, William and Hollier,
Mark and Unger, Elizabeth},
title = {Implementation of exon arrays: alternative splicing during T-cell
proliferation as determined by whole genome analysis},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {496},
number = {1},
abstract = {BACKGROUND:The contribution of alternative splicing and isoform expression
to cellular response is emerging as an area of considerable interest,
and the newly developed exon arrays allow for systematic study of
these processes. We use this pilot study to report on the feasibility
of exon array implementation looking to replace the 3' in vitro transcription
expression arrays in our laboratory.One of the most widely studied
models of cellular response is T-cell activation from exogenous stimulation.
Microarray studies have contributed to our understanding of key pathways
activated during T-cell stimulation. We use this system to examine
whole genome transcription and alternate exon usage events that are
regulated during lymphocyte proliferation in an attempt to evaluate
the exon arrays.RESULTS:Peripheral blood mononuclear cells form healthy
donors were activated using phytohemagglutinin, IL2 and ionomycin
and harvested at 5 points over a 7 day period. Flow cytometry measured
cell cycle events and the Affymetrix exon array platform was used
to identify the gene expression and alternate exon usage changes.
Gene expression changes were noted in a total of 2105 transcripts,
and alternate exon usage identified in 472 transcript clusters. There
was an overlap of 263 transcripts which showed both differential
expression and alternate exon usage over time. Gene ontology enrichment
analysis showed a broader range of biological changes in biological
processes for the differentially expressed genes, which include cell
cycle, cell division, cell proliferation, chromosome segregation,
cell death, component organization and biogenesis and metabolic process
ontologies. The alternate exon usage ontological enrichments are
in metabolism and component organization and biogenesis. We focus
on alternate exon usage changes in the transcripts of the spliceosome
complex. The real-time PCR validation rates were 86% for transcript
expression and 71% for alternate exon usage.CONCLUSIONS:This study
illustrates that the Exon array technology has the potential to provide
information on both transcript expression and isoform usage, with
very little increase in expense.},
doi = {10.1186/1471-2164-11-496},
issn = {1471-2164},
pubmedid = {20840771},
url = {http://www.biomedcentral.com/1471-2164/11/496}
}
@ARTICLE{Whistler2009,
author = {Whistler, Toni and Fletcher, Mary and Lonergan, William and Zeng,
Xiao-R and Lin, Jin-Mann and LaPerriere, Arthur and Vernon, Suzanne
and Klimas, Nancy},
title = {Impaired immune function in Gulf War Illness},
journal = {BMC Medical Genomics},
year = {2009},
volume = {2},
pages = {12},
number = {1},
abstract = {BACKGROUND:Gulf War Illness (GWI) remains a serious health consequence
for at least 11,000 veterans of the first Gulf War in the early 1990s.
Our understanding of the health consequences that resulted remains
inadequate, and this is of great concern with another deployment
to the same theater of operations occurring now. Chronic immune cell
dysfunction and activation have been demonstrated in patients with
GWI, although the literature is not uniform. We exposed GWI patients
and matched controls to an exercise challenge to explore differences
in immune cell function measured by classic immune assays and gene
expression profiling.METHODS:This pilot study enrolled 9 GWI cases
identified from the Department of Veterans Affairs GWI registry,
and 11 sedentary control veterans who had not been deployed to the
Persian Gulf and were matched to cases by sex, body mass index (BMI)
and age. We measured peripheral blood cell numbers, NK cytotoxicity,
cytokines and expression levels of 20,000 genes immediately before,
immediately after and 4 hours following a standard bicycle ergometer
exercise challenge.RESULTS:A repeated-measures analysis of variance
revealed statistically significant differences for three NK cell
subsets and NK cytotoxicity between cases and controls (p < 0.05).
Linear regression analysis correlating NK cell numbers to the gene
expression profiles showed high correlation of genes associated with
NK cell function, serving as a biologic validation of both the in
vitro assays and the microarray platform. Intracellular perforin
levels in NK and CD8 T-cells trended lower and showed a flatter profile
in GWI cases than controls, as did the expression levels of the perforin
gene PRF1. Genes distinguishing cases from controls were associated
with the glucocorticoid signaling pathway.CONCLUSION:GWI patients
demonstrated impaired immune function as demonstrated by decreased
NK cytotoxicity and altered gene expression associated with NK cell
function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated
mediators of the stress response (including salivary cortisol) were
also altered in GWI cases compared to control subjects. An interesting
and potentially important observation was that the exercise challenge
augments these differences, with the most significant effects observed
immediately after the stressor, possibly implicating some block in
the NK and CD8 T-cells ability to respond to "stress-mediated activation".
This has positive implications for the development of laboratory
diagnostic tests for this syndrome and provides a paradigm for exploration
of the immuno-physiological mechanisms that are operating in GWI,
and similar complex syndromes. Our results do not necessarily elucidate
the cause of GWI, but they do reveal a role for immune cell dysfunction
in sustaining illness.},
doi = {10.1186/1755-8794-2-12},
issn = {1755-8794},
pubmedid = {19265525},
url = {http://www.biomedcentral.com/1755-8794/2/12}
}
@ARTICLE{Whitaker2011,
author = {Whitaker, K. W. and Neumeister, H. and Huffman, L. S. and Kidd, C.
E. and Preuss, T. and Hofmann, H. A.},
title = {Serotonergic modulation of startle-escape plasticity in an African
cichlid fish: a single-cell molecular and physiological analysis
of a vital neural circuit},
journal = {J Neurophysiol},
year = {2011},
volume = {106},
pages = {127-137},
number = {1},
abstract = {Social life affects brain function at all levels, including gene expression,
neurochemical balance, and neural circuits. We have previously shown
that in the cichlid fish Astatotilapia burtoni brightly colored,
socially dominant (DOM) males face a trade-off between reproductive
opportunities and increased predation risk. Compared with camouflaged
subordinate (SUB) males, DOMs exposed to a loud sound pip display
higher startle responsiveness and increased excitability of the Mauthner
cell (M-cell) circuit that governs this behavior. Using behavioral
tests, intracellular recordings, and single-cell molecular analysis,
we show here that serotonin (5-HT) modulates this socially regulated
plasticity via the 5-HT receptor subtype 2 (5-HTR2). Specifically,
SUBs display increased sensitivity to pharmacological manipulation
of 5-HTR2 compared with DOMs in both startle-escape behavior and
electrophysiological properties of the M-cell. Immunohistochemistry
showed serotonergic varicosities around the M-cells, further suggesting
that 5-HT impinges directly onto the startle-escape circuitry. To
determine whether the effects of 5-HTR2 are pre- or postsynaptic,
and whether other 5-HTR subtypes are involved, we harvested the mRNA
from single M-cells via cytoplasmic aspiration and found that 5-HTR
subtypes 5A and 6 are expressed in the M-cell. 5-HTR2, however, was
absent, suggesting that it affects M-cell excitability through a
presynaptic mechanism. These results are consistent with a role for
5-HT in modulating startle plasticity and increase our understanding
of the neural and molecular basis of a trade-off between reproduction
and predation.},
doi = {10.1152/jn.01126.2010},
eprint = {http://jn.physiology.org/cgi/reprint/106/1/127.pdf},
url = {http://jn.physiology.org/cgi/content/abstract/106/1/127}
}
@ARTICLE{White2012,
author = {White, Andrea T. and Light, Alan R. and Hughen, Ronald W. and VanHaitsma,
Timothy A. and Light, Kathleen C.},
title = {Differences in Metabolite-Detecting, Adrenergic, and Immune Gene
Expression After Moderate Exercise in Patients With Chronic Fatigue
Syndrome, Patients With Multiple Sclerosis, and Healthy Controls},
journal = {Psychosom Med},
year = {2012},
volume = {74},
pages = {46-54},
number = {1},
abstract = {ObjectiveChronic fatigue syndrome (CFS) and multiple sclerosis (MS)
are characterized by debilitating fatigue, yet evaluation of this
symptom is subjective. We examined metabolite-detecting, adrenergic,
and immune gene expression (messenger ribonucleic acid [mRNA]) in
patients with CFS (n = 22) versus patients with MS (n = 20) versus
healthy controls (n = 23) and determined their relationship to fatigue
and pain before and after exercise. MethodsBlood samples and fatigue
and pain ratings were obtained at baseline and 0.5, 8, 24, and 48
hours after sustained moderate exercise. Leukocyte mRNA of four metabolite-detecting
receptors (acid-sensing ion channel 3, purinergic type 2X4 and 2X5
receptors, and transient receptor potential vanilloid type 1) and
four adrenergic (-2a, {beta}-1, and {beta}-2 receptors and catechol-O-methyltransferase)
and five immune markers (CD14, toll-like receptor 4 [TLR4], interleukin
[IL] 6, IL-10, and lymphotoxin ) was examined using quantitative
polymerase chain reaction. ResultsPatients with CFS had greater postexercise
increases in fatigue and pain (10-29 points above baseline, p < .001)
and greater mRNA increases in purinergic type 2X4 receptor, transient
receptor potential vanilloid type 1, CD14, and all adrenergic receptors
than controls (mean {+/-} standard error = 1.3 {+/-} 0.14- to 3.4
{+/-} 0.90-fold increase above baseline, p = .04-.005). Patients
with CFS with comorbid fibromyalgia (n = 18) also showed greater
increases in acid-sensing ion channel 3 and purinergic type 2X5 receptors
(p < .05). Patients with MS had greater postexercise increases than
controls in {beta}-1 and {beta}-2 adrenergic receptor expressions
(1.4 {+/-} 0.27- and 1.3 {+/-} 0.06-fold increases, respectively,
p = .02 and p < .001) and greater decreases in TLR4 (p = .02). In
MS, IL-10 and TLR4 decreases correlated with higher fatigue scores.
ConclusionsPostexercise mRNA increases in metabolite-detecting receptors
were unique to patients with CFS, whereas both patients with MS and
patients with CFS showed abnormal increases in adrenergic receptors.
Among patients with MS, greater fatigue was correlated with blunted
immune marker expression.},
doi = {10.1097/PSY.0b013e31824152ed},
eprint = {http://www.psychosomaticmedicine.org/cgi/reprint/74/1/46.pdf},
url = {http://www.psychosomaticmedicine.org/cgi/content/abstract/74/1/46}
}
@ARTICLE{White2005,
author = {White, Christine A and Salamonsen, Lois A},
title = {A guide to issues in microarray analysis: application to endometrial
biology},
journal = {Reproduction},
year = {2005},
volume = {130},
pages = {1--13},
number = {1},
month = jul,
abstract = {Within the last decade, the development of DNA microarray technology
has enabled the simultaneous measurement of thousands of gene transcripts
in a biological sample. Conducting a microarray study is a multi-step
process; starting with a well-defined biological question, moving
through experimental design, target RNA preparation, microarray hybridisation,
image acquisition and data analysis - finishing with a biological
interpretation requiring further study. Advances continue to be made
in microarray quality and methods of statistical analysis, improving
the reliability and therefore appeal of microarray analysis for a
wide range of biological questions. The purpose of this review is
to provide both an introduction to microarray methodology, as well
as a practical guide to the use of microarrays for gene expression
analysis, using endometrial biology as an example of the applications
of this technology. While recommendations are based on previous experience
in our laboratory, this review also summarises the methods currently
considered to be best practice in the field.},
url = {http://www.reproduction-online.org/cgi/content/abstract/130/1/1}
}
@ARTICLE{White2005a,
author = {White, C.A. and Dimitriadis, E. and Sharkey, A.M. and Salamonsen,
L.A.},
title = {Interleukin-11 inhibits expression of insulin-like growth factor
binding protein-5 mRNA in decidualizing human endometrial stromal
cells},
journal = {Mol. Hum. Reprod.},
year = {2005},
volume = {11},
pages = {649--658},
number = {9},
month = sep,
abstract = {Differentiation of endometrial stromal cells into decidual cells is
essential for successful embryo implantation. Interleukin (IL)-11
signalling is critical for normal decidualization in the mouse. The
expression of IL-11 and its receptors during the menstrual cycle,
and the effect of exogenous IL-11 on the decidualization of human
endometrial stromal cells in vitro, suggests a role for this cytokine
in human decidualization. As the downstream target genes of IL-11
are also likely to be critical mediators of this process, this study
aimed to identify genes regulated by IL-11 in decidualizing human
endometrial stromal cells in vitro. Stromal cells isolated from endometrial
biopsies were decidualized with 17{beta} estradiol (E) and medroxyprogesterone
acetate (EP) in the presence or absence of exogenous IL-11, and total
RNA used for cDNA microarray analysis and real-time RT-PCR. Microarray
analysis revealed 16 up-regulated and 11 down-regulated cDNAs in
EP + IL-11-treated compared with EP-treated cells. The most down-regulated
gene was insulin-like growth factor binding protein-5 (IGFBP-5) (3.6-fold).
Using real-time RT-PCR, IL-11 was confirmed to decrease IGFBP-5 transcript
abundance 102-fold (P = 0.016; n = 6). No difference in IGFBP-5 immunostaining
intensity was detected in stromal cells decidualized in the presence
or absence of IL-11, and there was no effect of exogenous IGFBP-5
on the progression of steroid-induced in vitro decidualization. Interactions
between IL-11 and its target genes, including IGFBP-5, may contribute
to the regulation of decidualization and/or mediate communication
between the decidua and invading trophoblast at implantation.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/11/9/649}
}
@ARTICLE{White2010,
author = {White, Colin and Khurana, Hema and Gnatenko, Dmitri and Li, Zhigang
and Odze, Robert and Sacks, David and Schmidt, Valentina},
title = {IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma},
journal = {BMC Gastroenterology},
year = {2010},
volume = {10},
pages = {125},
number = {1},
abstract = {BACKGROUND:IQGAP1 and IQGAP2 are homologous members of the IQGAP family
of scaffold proteins. Accumulating evidence implicates IQGAPs in
tumorigenesis. We recently reported that IQGAP2 deficiency leads
to the development of hepatocellular carcinoma (HCC) in mice. In
the current study we extend these findings, and investigate IQGAP1
and IQGAP2 expression in human HCC. METHODS:IQGAP1 and IQGAP2 protein
expression was assessed by Western blotting and immunohistochemistry.
IQGAP mRNA was measured by quantitative RT-PCR. The methylation status
of the Iqgap2 promoter was determined by pyrosequencing of bisulfite-treated
genomic DNA.RESULTS:IQGAP1 and IQGAP2 expression was reciprocally
altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical
staining of 82 HCC samples showed that IQGAP2 protein expression
was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%).
No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4
(100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while
IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%),
respectively. Although the Iqgap2 promoter was not hypermethylated
in HCC at any of the 25 CpG sites studied (N=17), IQGAP2 mRNA levels
were significantly lower in HCC specimens (N=23) than normal livers
(N=6). CONCLUSIONS:We conclude that increased IQGAP1 and/or decreased
IQGAP2 contribute to the pathogenesis of human HCC. Furthermore,
downregulation of IQGAP2 in HCC occurs independently of hypermethylation
of the Iqgap2 promoter. Immunostaining of IQGAP1 and IQGAP2 may aid
in the diagnosis of HCC, and their pharmacologic modulation may represent
a novel therapeutic strategy for the treatment of liver cancer. },
doi = {10.1186/1471-230X-10-125},
issn = {1471-230X},
pubmedid = {20977743},
url = {http://www.biomedcentral.com/1471-230X/10/125}
}
@ARTICLE{White2011a,
author = {White, Judith and Gilbert, Jack and Hill, Graham and Hill, Edward
and Huse, Susan M. and Weightman, Andrew J. and Mahenthiralingam,
Eshwar},
title = {Culture-Independent Analysis of Bacterial Fuel Contamination Provides
Insight into the Level of Concordance with the Standard Industry
Practice of Aerobic Cultivation},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {4527-4538},
number = {13},
abstract = {Bacterial diversity in contaminated fuels has not been systematically
investigated using cultivation-independent methods. The fuel industry
relies on phenotypic cultivation-based contaminant identification,
which may lack accuracy and neglect difficult-to-culture taxa. By
the use of industry practice aerobic cultivation, 16S rRNA gene sequencing,
and strain genotyping, a collection of 152 unique contaminant isolates
from 54 fuel samples was assembled, and a dominance of Pseudomonas
(21%), Burkholderia (7%), and Bacillus (7%) was demonstrated. Denaturing
gradient gel electrophoresis (DGGE) of 15 samples revealed Proteobacteria
and Firmicutes to be the most abundant phyla. When 16S rRNA V6 gene
pyrosequencing of four selected fuel samples (indicated by "JW")
was performed, Betaproteobacteria (42.8%) and Gammaproteobacteria
(30.6%) formed the largest proportion of reads; the most abundant
genera were Marinobacter (15.4%; JW57), Achromobacter (41.6%; JW63),
Burkholderia (80.7%; JW76), and Halomonas (66.2%; JW78), all of which
were also observed by DGGE. However, the Clostridia (38.5%) and Deltaproteobacteria
(11.1%) identified by pyrosequencing in sample JW57 were not observed
by DGGE or aerobic culture. Genotyping revealed three instances where
identical strains were found: (i) a Pseudomonas sp. strain recovered
from 2 different diesel fuel tanks at a single industrial site; (ii)
a Mangroveibacter sp. strain isolated from 3 biodiesel tanks at a
single refinery site; and (iii) a Burkholderia vietnamiensis strain
present in two unrelated automotive diesel samples. Overall, aerobic
cultivation of fuel contaminants recovered isolates broadly representative
of the phyla and classes present but lacked accuracy by overrepresenting
members of certain groups such as Pseudomonas.},
doi = {10.1128/AEM.02317-10},
eprint = {http://aem.asm.org/cgi/reprint/77/13/4527.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/13/4527}
}
@ARTICLE{White2008,
author = {White, Jessica and Pacey-Miller, Toni and Bundock, Peter and Henry,
Robert},
title = {Differential LongSAGE tag abundance analysis in a barley seed germination
time course and validation with relative real-time RT-PCR},
journal = {Plant Science},
year = {2008},
volume = {175},
pages = {858--867},
number = {6},
month = dec,
abstract = {A Long Serial Analysis of Gene Expression (LongSAGE) approach was
employed to identify changes in mRNA transcript abundance in a time
course of malting barley (Hordeum vulgare L.). Statistical analyses
confidently identified 57 LongSAGE sequence tags as having significant
changes in abundance between points in the time course. Eight of
the genes which correspond to these tags were targeted for validation
by relative real-time reverse transcriptase PCR (RT-PCR) analysis.
Each gene was analysed by SYBR® Green detection in grain sampled
at each of four time points from dry seed to grain germinated to
120 h post-steeping. Among the genes examined are alpha-amylase type
B, a key starch degrading enzyme involved in germination (1-3,1-4)-beta-d-glucanase,
the major cell wall degrading enzyme, and cysteine proteinase EP-B,
an important enzyme of proteolysis in barley seed germination. These
three transcripts show significant up-regulation at 48 h post-steeping
and remain significantly elevated throughout malting. These results
provide transcriptional data to support the understanding of how
the relative rates of protein and carbohydrate modification contribute
to malting and brewing. mRNA abundance levels observed using real-time
RT-PCR show good correlation with the data obtained from the LongSAGE
study. This confirms the sensitivity of detection obtainable with
SAGE technology and validates the patterns of change of transcript
abundance exhibited by some key genes for barley seed germination.},
issn = {0168-9452},
keywords = {Germination, Hordeum vulgare, Real-time reverse transcriptase PCR,
Long Serial Analysis of Gene Expression (longSAGE)},
url = {http://www.sciencedirect.com/science/article/B6TBH-4TDC08H-1/2/43fe24f3a595fdcf0fbf068ba43c4516}
}
@ARTICLE{White2011,
author = {White, Kevin and Loughlin, Lynn and Maqbool, Zakia and Nilsen, Margaret
and McClure, John and Dempsie, Yvonne and Baker, Andrew H. and MacLean,
Margaret R.},
title = {Serotonin transporter, sex, and hypoxia: microarray analysis in the
pulmonary arteries of mice identifies genes with relevance to human
PAH},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {417--437},
number = {8},
month = apr,
abstract = {Pulmonary arterial hypertension (PAH) is up to threefold more prevalent
in women than men. Female mice overexpressing the serotonin transporter
(SERT; SERT+ mice) exhibit PAH and exaggerated hypoxia-induced PAH,
whereas male SERT+ mice remain unaffected. To further investigate
these sex differences, microarray analysis was performed in the pulmonary
arteries of normoxic and chronically hypoxic female and male SERT+
mice. Quantitative RT-PCR analysis was employed for validation of
the microarray data. In relevant groups, immunoblotting was performed
for genes of interest (CEBP{beta}, CYP1B1, and FOS). To translate
clinical relevance to our findings, CEBP{beta}, CYP1B1, and FOS mRNA
and protein expression was assessed in pulmonary artery smooth muscle
cells (PASMCs) derived from idiopathic PAH (IPAH) patients and controls.
In female SERT+ mice, multiple pathways with relevance to PAH were
altered. This was also observed in chronically hypoxic female SERT+
mice. We selected 10 genes of interest for qRT-PCR analysis (FOS,
CEBP{beta}, CYP1B1, MYL3, HAMP2, LTF, PLN, NPPA, UCP1, and C1S),
and 100% concordance was reported. Protein expression of three selected
genes, CEBP{beta}, CYP1B1, FOS, was also upregulated in female SERT+
mice. Serotonin and 17{beta}-estradiol increased CEBP{beta}, CYP1B1,
and FOS protein expression in PASMCs. In addition, CEBP{beta}, CYP1B1,
and FOS mRNA and protein expression was also increased in PASMCs
derived from IPAH patients. Here, we have identified a number of
genes that may predispose female SERT+ mice to PAH, and these findings
may also be relevant to human PAH.},
comment = {10.1152/physiolgenomics.00249.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/8/417}
}
@ARTICLE{White2005b,
author = {White, Peter and Brestelli, John E. and Kaestner, Klaus H. and Greenbaum,
Linda E.},
title = {Identification of Transcriptional Networks during Liver Regeneration},
journal = {J. Biol. Chem.},
year = {2005},
volume = {280},
pages = {3715--3722},
number = {5},
month = feb,
abstract = {The molecular analysis of mammalian cellular proliferation in vivo
is limited in most organ systems by the low turnover and/or the asynchronous
nature of cell cycle progression. A notable exception is the partial
hepatectomy model, in which quiescent hepatocytes reenter the cell
cycle and progress in a synchronous fashion. Here we have exploited
this model to identify regulatory networks operative in the mammalian
cell cycle. We performed microarray-based expression profiling on
livers 0-40 h post-hepatectomy corresponding to G0, G1, and S phases.
Differentially expressed genes were identified using the statistical
analysis program PaGE (Patterns from Gene Expression), which was
highly accurate as confirmed by quantitative reverse transcription-PCR
of randomly selected targets. A shift in the transcriptional program
from genes involved in lipid and hormone biosynthesis in the quiescent
liver to those contributing to cytoskeleton assembly and DNA synthesis
in the proliferating liver was demonstrated by biological theme analysis.
In a novel approach, we employed computational pathway analysis tools
to identify specific regulatory networks operative at various stages
of the cell cycle. This allowed us to identify a large cluster of
genes controlling mitotic spindle assembly and checkpoint control
at the 40-h time point as regulated at the mRNA level in vivo.},
url = {http://www.jbc.org/cgi/content/abstract/280/5/3715}
}
@ARTICLE{White2008a,
author = {White, Peter and Lee May, Catherine and Lamounier, Rodrigo N. and
Brestelli, John E. and Kaestner, Klaus H.},
title = {Defining Pancreatic Endocrine Precursors and Their Descendants},
journal = {Diabetes},
year = {2008},
volume = {57},
pages = {654--668},
number = {3},
month = mar,
abstract = {OBJECTIVE--The global incidence of diabetes continues to increase.
Cell replacement therapy and islet transplantation offer hope, especially
for severely affected patients. Efforts to differentiate insulin-producing
{beta}-cells from progenitor or stem cells require knowledge of the
transcriptional programs that regulate the development of the endocrine
pancreas. RESEARCH DESIGN AND METHODS--Differentiation toward the
endocrine lineage is dependent on the transcription factor Neurogenin
3 (Neurog3, Ngn3). We utilize a Neurog3-enhanced green fluorescent
protein knock-in mouse model to isolate endocrine progenitor cells
from embryonic pancreata (embryonic day [E]13.5 through E17.5). Using
advanced genomic approaches, we generate a comprehensive gene expression
profile of these progenitors and their immediate descendants. RESULTS--A
total of 1,029 genes were identified as being temporally regulated
in the endocrine lineage during fetal development, 237 of which are
transcriptional regulators. Through pathway analysis, we have modeled
regulatory networks involving these proteins that highlight the complex
transcriptional hierarchy governing endocrine differentiation. CONCLUSIONS--We
have been able to accurately capture the gene expression profile
of the pancreatic endocrine progenitors and their descendants. The
list of temporally regulated genes identified in fetal endocrine
precursors and their immediate descendants provides a novel and important
resource for developmental biologists and diabetes researchers alike.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/57/3/654}
}
@ARTICLE{White2009,
author = {White, Richard and Blainey, Paul and Fan, H Christina and Quake,
Stephen},
title = {Digital PCR provides sensitive and absolute calibration for high
throughput sequencing},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {116},
number = {1},
abstract = {BACKGROUND:Next-generation DNA sequencing on the 454, Solexa, and
SOLiD platforms requires absolute calibration of the number of molecules
to be sequenced. This requirement has two unfavorable consequences.
First, large amounts of sample-typically micrograms-are needed for
library preparation, thereby limiting the scope of samples which
can be sequenced. For many applications, including metagenomics and
the sequencing of ancient, forensic, and clinical samples, the quantity
of input DNA can be critically limiting. Second, each library requires
a titration sequencing run, thereby increasing the cost and lowering
the throughput of sequencing.RESULTS:We demonstrate the use of digital
PCR to accurately quantify 454 and Solexa sequencing libraries, enabling
the preparation of sequencing libraries from nanogram quantities
of input material while eliminating costly and time-consuming titration
runs of the sequencer. We successfully sequenced low-nanogram scale
bacterial and mammalian DNA samples on the 454 FLX and Solexa DNA
sequencing platforms. This study is the first to definitively demonstrate
the successful sequencing of picogram quantities of input DNA on
the 454 platform, reducing the sample requirement more than 1000-fold
without pre-amplification and the associated bias and reduction in
library depth.CONCLUSION:The digital PCR assay allows absolute quantification
of sequencing libraries, eliminates uncertainties associated with
the construction and application of standard curves to PCR-based
quantification, and with a coefficient of variation close to 10%,
is sufficiently precise to enable direct sequencing without titration
runs.},
doi = {10.1186/1471-2164-10-116},
issn = {1471-2164},
pubmedid = {19298667},
url = {http://www.biomedcentral.com/1471-2164/10/116}
}
@ARTICLE{White2003,
author = {White, S J and Sterrenburg, E and van Ommen, G-J B and den Dunnen,
J T and Breuning, M H},
title = {An alternative to FISH: detecting deletion and duplication carriers
within 24 hours},
journal = {J. Med. Genet.},
year = {2003},
volume = {40},
pages = {e113--},
number = {10},
month = oct,
url = {http://jmg.bmj.com/content/40/10/e113.full.pdf?sid=75159f43-c4f9-4f0c-ae50-3798561fff0d}
}
@ARTICLE{Whiteford2007,
author = {Whiteford, Craig C. and Bilke, Sven and Greer, Braden T. and Chen,
Qingrong and Braunschweig, Till A. and Cenacchi, Nicola and Wei,
Jun S. and Smith, Malcolm A. and Houghton, Peter and Morton, Christopher
and Reynolds, C. Patrick and Lock, Richard and Gorlick, Richard and
Khanna, Chand and Thiele, Carol J. and Takikita, Mikiko and Catchpoole,
Daniel and Hewitt, Stephen M. and Khan, Javed},
title = {Credentialing Preclinical Pediatric Xenograft Models Using Gene Expression
and Tissue Microarray Analysis},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {32--40},
number = {1},
month = jan,
abstract = {Human tumor xenografts have been used extensively for rapid screening
of the efficacy of anticancer drugs for the past 35 years. The selection
of appropriate xenograft models for drug testing has been largely
empirical and has not incorporated a similarity to the tumor type
of origin at the molecular level. This study is the first comprehensive
analysis of the transcriptome of a large set of pediatric xenografts,
which are currently used for preclinical drug testing. Suitable models
representing the tumor type of origin were identified. It was found
that the characteristic expression patterns of the primary tumors
were maintained in the corresponding xenografts for the majority
of samples. Because a prerequisite for developing rationally designed
drugs is that the target is expressed at the protein level, we developed
tissue arrays from these xenografts and corroborated that high mRNA
levels yielded high protein levels for two tested genes. The web
database and availability of tissue arrays will allow for the rapid
confirmation of the expression of potential targets at both the mRNA
and the protein level for molecularly targeted agents. The database
will facilitate the identification of tumor markers predictive of
response to tested agents as well as the discovery of new molecular
targets. [Cancer Res 2007;67(1):32-40]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/1/32}
}
@ARTICLE{Whitelaw2010,
author = {Whitelaw, Nadia and Chong, Suyinn and Morgan, Daniel and Nestor,
Colm and Bruxner, Timothy and Ashe, Alyson and Lambley, Eleanore
and Meehan, Richard and Whitelaw, Emma},
title = {Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a
and Trim28, cause increased phenotypic noise},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R111},
number = {11},
abstract = {BACKGROUND:Inbred individuals reared in controlled environments display
considerable variance in many complex traits but the underlying cause
of this intangible variation has been an enigma. Here we show that
two modifiers of epigenetic gene silencing play a critical role in
the process.RESULTS:Inbred mice heterozygous for a null mutation
in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein
28 (Trim28) show greater coefficients of variance in body weight
than their wild-type littermates. Trim28 mutants additionally develop
metabolic syndrome and abnormal behavior with incomplete penetrance.
Genome-wide gene expression analyses identified 284 significantly
dysregulated genes in Trim28 heterozygote mutants compared to wild-type
mice, with Mas1, which encodes a G-protein coupled receptor implicated
in lipid metabolism, showing the greatest average change in expression
(7.8-fold higher in mutants). This gene also showed highly variable
expression between mutant individuals.CONCLUSIONS:These studies provide
a molecular explanation of developmental noise in whole organisms
and suggest that faithful epigenetic control of transcription is
central to suppressing deleterious levels of phenotypic variation.
These findings have broad implications for understanding the mechanisms
underlying sporadic and complex disease in humans.},
doi = {10.1186/gb-2010-11-11-r111},
issn = {1465-6906},
pubmedid = {21092094},
url = {http://genomebiology.com/2010/11/11/R111}
}
@ARTICLE{Whiteley2008,
author = {Whiteley, Andrew R. and Derome, Nicolas and Rogers, Sean M. and St-Cyr,
Jerome and Laroche, Jerome and Labbe, Aurelie and Nolte, Arne and
Renaut, Sebastien and Jeukens, Julie and Bernatchez, Louis},
title = {The Phenomics and Expression Quantitative Trait Locus Mapping of
Brain Transcriptomes Regulating Adaptive Divergence in Lake Whitefish
Species Pairs (Coregonus sp.)},
journal = {Genetics},
year = {2008},
volume = {180},
pages = {147--164},
number = {1},
month = sep,
abstract = {We used microarrays and a previously established linkage map to localize
the genetic determinants of brain gene expression for a backcross
family of lake whitefish species pairs (Coregonus sp.). Our goals
were to elucidate the genomic distribution and sex specificity of
brain expression QTL (eQTL) and to determine the extent to which
genes controlling transcriptional variation may underlie adaptive
divergence in the recently evolved dwarf (limnetic) and normal (benthic)
whitefish. We observed a sex bias in transcriptional genetic architecture,
with more eQTL observed in males, as well as divergence in genome
location of eQTL between the sexes. Hotspots of nonrandom aggregations
of up to 32 eQTL in one location were observed. We identified candidate
genes for species pair divergence involved with energetic metabolism,
protein synthesis, and neural development on the basis of colocalization
of eQTL for these genes with eight previously identified adaptive
phenotypic QTL and four previously identified outlier loci from a
genome scan in natural populations. Eighty-eight percent of eQTL-phenotypic
QTL colocalization involved growth rate and condition factor QTL,
two traits central to adaptive divergence between whitefish species
pairs. Hotspots colocalized with phenotypic QTL in several cases,
revealing possible locations where master regulatory genes, such
as a zinc-finger protein in one case, control gene expression directly
related to adaptive phenotypic divergence. We observed little evidence
of colocalization of brain eQTL with behavioral QTL, which provides
insight into the genes identified by behavioral QTL studies. These
results extend to the transcriptome level previous work illustrating
that selection has shaped recent parallel divergence between dwarf
and normal lake whitefish species pairs and that metabolic, more
than morphological, differences appear to play a key role in this
divergence.},
url = {http://www.genetics.org/cgi/content/abstract/180/1/147}
}
@ARTICLE{Whitfield2011,
author = {Whitfield, A. E. and Rotenberg, D. and Aritua, V. and Hogenhout,
S. A.},
title = {Analysis of expressed sequence tags from Maize mosaic rhabdovirus-infected
gut tissues of Peregrinus maidis reveals the presence of key components
of insect innate immunity},
journal = {Insect Molecular Biology},
year = {2011},
volume = {20},
pages = {225--242},
number = {2},
abstract = {Abstract The corn planthopper, Peregrinus maidis, causes direct feeding
damage to plants and transmits Maize mosaic rhabdovirus (MMV) in
a persistent-propagative manner. MMV must cross several insect tissue
layers for successful transmission to occur, and the gut serves as
an important barrier for rhabdovirus transmission. In order to facilitate
the identification of proteins that may interact with MMV either
by facilitating acquisition or responding to virus infection, we
generated and analysed the gut transcriptome of P. maidis. From two
normalized cDNA libraries, we generated a P. maidis gut transcriptome
composed of 20Â 771 expressed sequence tags (ESTs). Assembly of the
sequences yielded 1860 contigs and 14Â 032 singletons, and biological
roles were assigned to 5793 (36%). Comparison of P. maidis ESTs with
other insect amino acid sequences revealed that P. maidis shares
greatest sequence similarity with another hemipteran, the brown planthopper
Nilaparvata lugens. We identified 202 P. maidis transcripts with
putative homology to proteins associated with insect innate immunity,
including those implicated in the Toll, Imd, JAK/STAT, Jnk and the
small-interfering RNA-mediated pathways. Sequence comparisons between
our P. maidis gut EST collection and the currently available National
Center for Biotechnology Information EST database collection for
Ni. lugens revealed that a pathogen recognition receptor in the Imd
pathway, peptidoglycan recognition protein-long class (PGRP-LC),
is present in these two members of the family Delphacidae; however,
these recognition receptors are lacking in the model hemipteran Acyrthosiphon
pisum. In addition, we identified sequences in the P. maidis gut
transcriptome that share significant amino acid sequence similarities
with the rhabdovirus receptor molecule, acetylcholine receptor (AChR),
found in other hosts. This EST analysis sheds new light on immune
response pathways in hemipteran guts that will be useful for further
dissecting innate defence response pathways to rhabdovirus infection.},
doi = {10.1111/j.1365-2583.2010.01060.x},
issn = {1365-2583},
keywords = {arthropod vector, Hemiptera, Rhabdoviridae, transcriptome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2583.2010.01060.x}
}
@ARTICLE{Whitney2009,
author = {Whitney, Irene E. and Raven, Mary A. and Ciobanu, Daniel C. and Williams,
Robert W. and Reese, Benjamin E.},
title = {Multiple Genes on Chromosome 7 Regulate Dopaminergic Amacrine Cell
Number in the Mouse Retina},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {1996--2003},
number = {5},
month = may,
abstract = {PURPOSE. The size of neuronal populations is modulated by gene variants
that influence cell production and survival, in turn influencing
neuronal connectivity, function, and disease risk. The size of the
dopaminergic amacrine (DA) cell population is a highly heritable
trait exhibiting sixfold variation among inbred strains of mice and
is used here to identify genes that modulate the number of DA cells.
METHODS. The entire population was counted in retinal wholemounts
from 37 genetically defined lines of mice, including six standard
inbred strains, 25 recombinant inbred strains (AXB/BXA), reciprocal
F1 hybrids, a chromosome (Chr) 7 consomic line, and three additional
genetically modified lines. RESULTS. Much of this variation was mapped
to a broad locus on Chr 7 (Dopaminergic amacrine cell number control,
Chr 7 [Dacnc7]). The Dacnc7 locus is flanked by two candidate genes
known to modulate the number of other types of retinal neuron--the
proapoptotic gene, Bax, and tyrosinase. The Tyr mutation was shown
to modulate DA cell number modestly, though in the direction opposite
that predicted. In contrast, Bax deficiency increased the population
fourfold. Bax expression was significantly greater in the A/J than
in the C57BL/6J strain, an effect that may be attributed to an SNP
in a p53 consensus binding site known to modulate transcription.
Finally, we note a strong candidate situated at the peak of the Dacnc7
locus, Lrrk1, a Parkinson's disease gene exhibiting missense mutations
segregating within the AXB/BXA cross. CONCLUSIONS. Multiple polymorphic
genes on Chr 7 modulate the size of the population of DA cells.},
url = {http://www.iovs.org/cgi/content/abstract/50/5/1996}
}
@ARTICLE{Whitney2011,
author = {Whitney, Irene E. and Raven, Mary A. and Lu, Lu and Williams, Robert
W. and Reese, Benjamin E.},
title = {A QTL on Chromosome 10 Modulates Cone Photoreceptor Number in the
Mouse Retina},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {3228--3236},
number = {6},
month = may,
abstract = {Purpose.This investigation examines the genetic sources of marked
variation in cone photoreceptor number among inbred lines of mice,
identifying candidate genes that may control the proliferation, differentiation,
or survival of this neuronal population. Methods.Cone photoreceptor
populations were counted in C57BL/6J (B6/J) and A/J strains, and
26 recombinant inbred (RI) strains derived from them. Eyes from RI
strains were also collected for microarray analysis. Quantitative
trait locus (QTL) analysis was carried out by simple and composite
interval mapping and validated using a consomic line. Candidate genes
were evaluated based on genetic variance between the parental strains
and analysis of gene expression. Expression data, deposited in GeneNetwork
(www.GeneNetwork.org), were used to generate a coexpression network
of established cone photoreceptor genes as a reference standard.
Results.B6/J has 70% more cone photoreceptors than A/J. A significant
QTL was mapped to chromosome 10 (Chr 10) and confirmed using B6.A<10>
mice. Of 19 positional candidate genes, one--the myeloblastosis oncogene
(Myb)--stood out. Myb has a potentially damaging missense mutation,
high retinal expression, and a known role in cell proliferation.
The ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (Enpp1)
was a second strong candidate, with an expression pattern that covaried
with cone photoreceptors and that was differentially expressed between
the parental strains. Enpp1 and several other candidate genes covaried
with multiple genes within the cone photoreceptor gene network. Conclusions.The
mouse retina shows marked variation in cone photoreceptor number,
some of which must be controlled by polymorphisms in a gene or genes
on Chr 10.},
comment = {10.1167/iovs.10-6693},
url = {http://www.iovs.org/cgi/content/abstract/52/6/3228}
}
@ARTICLE{Whitson2009,
author = {Whitson, Bryan A. and D'Cunha, Jonathan and Hoang, Chuong D. and
Wu, Baolin and Ikramuddin, Sayeed and Buchwald, Henry and Panoskaltsis-Mortari,
Angela and Kratzke, Robert A. and Miller, Jeffrey S. and Maddaus,
Michael A.},
title = {Minimally invasive versus open Roux-en-Y gastric bypass: effect on
immune effector cells},
journal = {Surgery for Obesity and Related Diseases},
year = {2009},
volume = {5},
pages = {181--193},
number = {2},
month = mar,
abstract = {Background Minimally invasive surgery (MIS) has several potential
benefits compared with the open approach, including potentially less
perioperative immunosuppression. Data characterizing the differential
stress responses have been limited to serum cytokine analyses and
animal studies. We hypothesized that the open approach to Roux-en-Y
gastric bypass (RYGB) has a more deleterious, negative, quantifiable
effect on the peripheral blood mononuclear cells than does the MIS
approach.Methods Patients undergoing open and MIS RYGB for morbid
obesity had blood samples collected preoperatively and postoperatively
on days 1 and 2 and at the first follow-up visit. The peripheral
blood mononuclear cells were isolated and analyzed for phenotype
using flow cytometry, natural killer cell cytotoxicity using 51-chromium
release assay, and gene expression using Affymetrix U133 Plus 2.0
microarray.Results Patient age and body mass index were similar between
the 2 groups. Postoperatively, differences within the open group
were seen for CD3+/CD16- (T lymphocytes), CD3-/CD16+ (natural killer
cells), CD3+/CD4+ (T-helper lymphocytes), and CD4/CD8 subsets (P
<.05). No differences were seen within the open group CD3+/CD8+ (cytotoxic
T lymphocytes) or within the MIS subsets. Between the 2 approaches,
no phenotypic differences were found, except for the postoperative
day 1 CD3+/CD16- (P <.05). Within each group, significant decreases
were found in cytotoxicity on days 1 and 2 compared with preoperatively
(P <.05). The cytotoxicity seen after MIS had returned to the preoperative
levels at the first follow-up visit, but the cytotoxicity after open
RYGB had not (P <.05). Between the 2 groups, the open group had greater
cytotoxic decreases than did the MIS group at postoperative days
1 and 2 (P <.05). Microarray analysis of the preoperative (n = 20)
and day 2 (n = 20) specimens identified a 20-gene signature that
correlated with the surgical approach.Conclusion Open RYGB surgery
causes greater inhibition of innate immunity than does MIS. This
inhibition was not accounted for by phenotypic changes. Gene expression
changes from surgical stress might represent the molecular basis
of this differential immune response.},
issn = {1550-7289},
keywords = {Minimally invasive surgery, Immune effector cell, Gastric bypass},
url = {http://www.sciencedirect.com/science/article/B7MD3-4TB77J5-1/2/5177bb03b6baa6cbf0da8332cd9374f1}
}
@ARTICLE{Wicker2004,
author = {Wicker, Linda S. and Chamberlain, Giselle and Hunter, Kara and Rainbow,
Dan and Howlett, Sarah and Tiffen, Paul and Clark, Jan and Gonzalez-Munoz,
Andrea and Cumiskey, Anne Marie and Rosa, Raymond L. and Howson,
Joanna M. and Smink, Luc J. and Kingsnorth, Amanda and Lyons, Paul
A. and Gregory, Simon and Rogers, Jane and Todd, John A. and Peterson,
Laurence B.},
title = {Fine Mapping, Gene Content, Comparative Sequencing, and Expression
Analyses Support Ctla4 and Nramp1 as Candidates for Idd5.1 and Idd5.2
in the Nonobese Diabetic Mouse},
journal = {J. Immunol.},
year = {2004},
volume = {173},
pages = {164--173},
number = {1},
month = jul,
abstract = {At least two loci that determine susceptibility to type 1 diabetes
in the NOD mouse have been mapped to chromosome 1, Idd5.1 (insulin-dependent
diabetes 5.1) and Idd5.2. In this study, using a series of novel
NOD.B10 congenic strains, Idd5.1 has been defined to a 2.1-Mb region
containing only four genes, Ctla4, Icos, Als2cr19, and Nrp2 (neuropilin-2),
thereby excluding a major candidate gene, Cd28. Genomic sequence
comparison of the two functional candidate genes, Ctla4 and Icos,
from the B6 (resistant at Idd5.1) and the NOD (susceptible at Idd5.1)
strains revealed 62 single nucleotide polymorphisms (SNPs), only
two of which were in coding regions. One of these coding SNPs, base
77 of Ctla4 exon 2, is a synonymous SNP and has been correlated previously
with type 1 diabetes susceptibility and differential expression of
a CTLA-4 isoform. Additional expression studies in this work support
the hypothesis that this SNP in exon 2 is the genetic variation causing
the biological effects of Idd5.1. Analysis of additional congenic
strains has also localized Idd5.2 to a small region (1.52 Mb) of
chromosome 1, but in contrast to the Idd5.1 interval, Idd5.2 contains
at least 45 genes. Notably, the Idd5.2 region still includes the
functionally polymorphic Nramp1 gene. Future experiments to test
the identity of Idd5.1 and Idd5.2 as Ctla4 and Nramp1, respectively,
can now be justified using approaches to specifically alter or mimic
the candidate causative SNPs.},
url = {http://www.jimmunol.org/cgi/content/abstract/173/1/164}
}
@ARTICLE{Wider2009,
author = {Wider, Christian and Lincoln, Sarah and Dachsel, Justus C. and Kapatos,
Gregory and Heckman, Michael G. and Diehl, Nancy N. and Papapetropoulos,
Spiridon and Mash, Deborah and Rajput, Alex and Rajput, Ali H. and
Dickson, Dennis W. and Wszolek, Zbigniew K. and Farrer, Matthew J.},
title = {GCH1 expression in human cerebellum from healthy individuals is not
gender dependant},
journal = {Neuroscience Letters},
year = {2009},
volume = {462},
pages = {73--75},
number = {1},
month = sep,
abstract = {Dopa-responsive dystonia (DRD) is a familial childhood-onset disease
characterized by fluctuating dystonia, associated with tremor and
parkinsonism in some patients. In most families the disease displays
autosomal dominant inheritance due to mutations in the GTP cyclohydrolase
1 gene (GCH1). Penetrance and symptom severity display strong female
predominance for which gender-specific GCH1 expression has been hypothesized.
In this study, GCH1 mRNA expression was measured in cerebellar tissue
from 66 healthy human subjects (30 women), and in cerebellar and
nigral tissue from eight individuals. No significant difference was
found between men and women with small effect sizes observed. Although
the correlation between cerebellar and nigral GCH1 expression remains
to be further examined, this exploratory study does not support gender-specific
GCH1 expression being the basis for the skewed gender distribution
observed in DRD patients.},
issn = {0304-3940},
keywords = {Dopa-responsive dystonia, DRD, GCH1 expression, Gender distribution},
url = {http://www.sciencedirect.com/science/article/B6T0G-4WN2XYB-1/2/d1466645aa9df844f8f392da572e20a5}
}
@ARTICLE{Widodo2010,
author = {Widodo,   and Broadley, Martin R. and Rose, Terry and Frei, Michael
and Pariasca-Tanaka, Juan and Yoshihashi, Tadashi and Thomson, Michael
and Hammond, John P. and Aprile, Alessio and Close, Timothy J. and
Ismail, Abdelbagi M. and Wissuwa, Matthias},
title = {Response to zinc deficiency of two rice lines with contrasting tolerance
is determined by root growth maintenance and organic acid exudation
rates, and not by zinc-transporter activity},
journal = {New Phytologist},
year = {2010},
volume = {186},
pages = {400--414},
number = {2},
abstract = {Summary * •Zinc (Zn)-deficient soils constrain rice (Oryza sativa)
production and cause Zn malnutrition. The identification of Zn-deficiency-tolerant
rice lines indicates that breeding might overcome these constraints.
Here, we seek to identify processes underlying Zn-deficiency tolerance
in rice at the physiological and transcriptional levels. * •A Zn-deficiency-tolerant
line RIL46 acquires Zn more efficiently and produces more biomass
than its nontolerant maternal line (IR74) at low [Zn]ext under field
conditions. We tested if this was the result of increased expression
of Zn2+ transporters; increased root exudation of deoxymugineic acid
(DMA) or low-molecular-weight organic acids (LMWOAs); and/or increased
root production. Experiments were performed in field and controlled
environment conditions. * •There was little genotypic variation
in transcript abundance of Zn-responsive root Zn2+-transporters between
the RIL46 and IR74. However, root exudation of DMA and LMWOA was
greater in RIL46, coinciding with increased root expression of putative
ligand-efflux genes. Adventitious root production was maintained
in RIL46 at low [Zn]ext, correlating with altered expression of root-specific
auxin-responsive genes. * •Zinc-deficiency tolerance in RIL46 is
most likely the result of maintenance of root growth, increased efflux
of Zn ligands, and increased uptake of Zn-ligand complexes at low
[Zn]ext; these traits are potential breeding targets.},
issn = {1469-8137},
keywords = {adventitious roots, deoxymugineic acid (DMA), microarray, Oryza sativa
(rice), transcriptional profiling},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2009.03177.x}
}
@ARTICLE{Wiebalk2007,
author = {Wiebalk, Katrin and Schmezer, Peter and Kropp, Silke and Chang-Claude,
Jenny and Celebi, Oktay and Debus, Jürgen and Bartsch, Helmut and
Popanda, Odilia},
title = {In vitro radiation-induced expression of XPC mRNA as a possible biomarker
for developing adverse reactions during radiotherapy},
journal = {Int. J. Cancer},
year = {2007},
volume = {121},
pages = {2340--2345},
number = {10},
abstract = {Abstract 10.1002/ijc.22981.abs Repair of radiation-induced DNA damage
is believed to play a critical role in developing adverse reactions
during radiotherapy. Ionizing radiation induces transcription of
several DNA repair genes including XPC as a part of the p53-transmitted
stress response. XPC gene induction was measured to analyze whether
it predicts occurrence of therapy-related acute side effects. Prostate
cancer patients (n = 406) receiving radiotherapy were monitored for
development of acute adverse effects using common toxicity criteria.
For gene induction analysis, lymphocytes from 99 patients were selected
according to their observed grade of clinical side effects. Cells
were irradiated in vitro with 5 Gy and analyzed after 4 hr for XPC
gene induction using reverse transcription and quantitative real-time
PCR. Analysis of modulation of XPC induction by personal, clinical
or lifestyle factors was included. Inter-individual induction of
XPC expression by ionizing radiation varied up to 20-fold (0.29–5.77)
and was significantly higher in current or exsmokers than in never-smokers
(p value: 0.008). Patients with XPC induction above the 90th percentile
compared to those with lower induction levels were at increased risk
of suffering from adverse reactions during radiotherapy (odds ratio
5.3, 95% confidence interval 1.2–24.5; adjusted for smoking). In
summary, XPC mRNA levels induced by ionizing radiation were shown
for the first time to be strongly affected by smoking and to be associated
with an approximately 5-fold increased risk for developing acute
side effects of radiotherapy. The predictive value of DNA damage-induced
XPC levels as a possible biomarker for radiosensitivity has to be
further investigated. © 2007 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {prostate cancer, quantitative RT-PCR, ionizing radiation, DNA damage
response, smoking},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.22981}
}
@ARTICLE{Wiebe2007,
author = {Wiebe, Peter O. and Kormish, Jay D. and Roper, Venus T. and Fujitani,
Yoshio and Alston, Ninche I. and Zaret, Kenneth S. and Wright, Christopher
V. E. and Stein, Roland W. and Gannon, Maureen},
title = {Ptf1a Binds to and Activates Area III, a Highly Conserved Region
of the Pdx1 Promoter That Mediates Early Pancreas-Wide Pdx1 Expression},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {4093--4104},
number = {11},
month = jun,
abstract = {The critical pancreatic transcription factor Pdx1 is expressed throughout
the pancreas early but enriched in insulin-producing {beta} cells
postnatally. Previous studies showed that the 5' conserved promoter
regions areas I and II (Pdx1PB) direct endocrine cell expression,
while an adjacent region (Pdx1XB) containing conserved area III directs
transient {beta}-cell expression. In this study, we used Cre-mediated
lineage tracing to track cells that activated these regions. Pdx1PBCre
mediated only endocrine cell recombination, while Pdx1XBCre directed
broad and early recombination in the developing pancreas. Also, a
reporter transgene containing areas I, II, and III was expressed
throughout the embryonic day 10.5 (E10.5) pancreas and gradually
became {beta} cell enriched, similar to endogenous Pdx1. These data
suggested that sequences within area III mediate early pancreas-wide
Pdx1 expression. Area III contains a binding site for PTF1, a transcription
factor complex essential for pancreas development. This site contributed
to area III-dependent reporter gene expression in the acinar AR42J
cell line, while PTF1 specifically trans-activated area III-containing
reporter expression in a nonpancreatic cell line. Importantly, Ptf1a
occupied sequences spanning the endogenous PTF1 site in area III
of E11.5 pancreatic buds. These data strongly suggest that PTF1 is
an important early activator of Pdx1 in acinar and endocrine progenitor
cells during pancreas development.},
url = {http://mcb.asm.org/cgi/content/abstract/27/11/4093}
}
@ARTICLE{Wieczorek2008,
author = {Wieczorek, Krzysztof and Hofmann, Julia and Blöchl, Andreas and
Szakasits, Dagmar and Bohlmann, Holger and Grundler, Florian M. W.},
title = {Arabidopsis endo-1,4-β-glucanases are involved in the formation
of root syncytia induced by Heterodera schachtii},
journal = {The Plant Journal},
year = {2008},
volume = {53},
pages = {336--351},
number = {2},
abstract = {Summary Cyst nematodes induce root syncytia with specific features
such as hypertrophy, increased metabolic activity and fusion with
adjacent cells. Cell walls of the syncytia undergo massive changes
such as thickening, local dissolution and formation of ingrowths.
Cell wall degrading and modifying proteins are apparently involved
in syncytium formation but detailed knowledge of this is still limited.
Therefore, we studied the regulation and function of the entire Arabidopsis
endo-1,4-β-glucanase gene family in syncytia induced by Heterodera
schachtii. Endo-1,4-β-glucanases hydrolyze the 1,4-β-glucosidic
linkages between glucose residues. Using semi-quantitative and quantitative
approaches we identified seven genes that are upregulated in syncytia.
Two of these genes, coding for secreted AtCel2 and membrane-bound
KOR3, are shoot-specific but show high expression in syncytia at
different developmental stages. In silico analysis of the promoter
regions of both genes compared with other genes with modified regulation
in nematode feeding sites did not reveal specific cis-acting elements
that could be related to specific transcription in syncytia. However,
motifs responsive to sugar and different plant hormones were identified.
Accordingly, treatments with sucrose, gibberellic acid and NAA induced
upregulation of AtCel2, whereas ABA triggered downregulation of both
AtCel2 and KOR3 in roots. As AtCel2 is related to degradation of
the cell wall matrix, we analysed the hemicellulose content in syncytia.
The measured values resembled the expression pattern of AtCel2. A
distinctly reduced number of females developed in cel2 and kor3 T-DNA
mutants, and we therefore conclude that endo-1,4-β-glucanases play
an important role in the formation and function of syncytia.},
issn = {1365-313X},
keywords = {cell wall, endo-1,4-β-glucanases, Genechip, Heterodera schachtii,
in situ RT-PCR, plant pathogens},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2007.03340.x}
}
@ARTICLE{Wiedemann2010,
author = {Wiedemann, Sonja M. and Mildner, Silke N. and Bonisch, Clemens and
Israel, Lars and Maiser, Andreas and Matheisl, Sarah and Straub,
Tobias and Merkl, Rainer and Leonhardt, Heinrich and Kremmer, Elisabeth
and Schermelleh, Lothar and Hake, Sandra B.},
title = {Identification and characterization of two novel primate-specific
histone H3 variants, H3.X and H3.Y},
journal = {J. Cell Biol.},
year = {2010},
volume = {190},
pages = {777--791},
number = {5},
month = sep,
abstract = {Nucleosomal incorporation of specialized histone variants is an important
mechanism to generate different functional chromatin states. Here,
we describe the identification and characterization of two novel
primate-specific histone H3 variants, H3.X and H3.Y. Their messenger
RNAs are found in certain human cell lines, in addition to several
normal and malignant human tissues. In keeping with their primate
specificity, H3.X and H3.Y are detected in different brain regions.
Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin
in a similar fashion to the known H3 variants. Importantly, we demonstrate
biochemically and by mass spectrometry that endogenous H3.Y protein
exists in vivo, and that stress stimuli, such as starvation and cellular
density, increase the abundance of H3.Y-expressing cells. Global
transcriptome analysis revealed that knockdown of H3.Y affects cell
growth and leads to changes in the expression of many genes involved
in cell cycle control. Thus, H3.Y is a novel histone variant involved
in the regulation of cellular responses to outside stimuli.},
url = {http://jcb.rupress.org/cgi/content/abstract/190/5/777}
}
@ARTICLE{Wiederholt2009,
author = {Wiederholt, Tonio and Heise, Ruth and Skazik, Claudia and Marquardt,
Yvonne and Joussen, Sylvia and Erdmann, Kati and Schröder, Henning
and Merk, Hans F. and Baron, Jens Malte},
title = {Calcium pantothenate modulates gene expression in proliferating human
dermal fibroblasts},
journal = {Experimental Dermatology},
year = {2009},
volume = {18},
pages = {969--978},
number = {11},
abstract = {Abstract:  Topical application of pantothenate is widely used in
clinical practice for wound healing. Previous studies identified
a positive effect of pantothenate on migration and proliferation
of cultured fibroblasts. However, these studies were mainly descriptive
with no molecular data supporting a possible model of its action.
In this study, we first established conditions for an in vitro model
of pantothenate wound healing and then analysed the molecular effects
of pantothenate. To test the functional effect of pantothenate on
dermal fibroblasts, cells were cultured and in vitro proliferation
tests were performed using a standardized scratch test procedure.
For all three donors analysed, a strong stimulatory effect of pantothenate
at a concentration of 20 μg/ml on the proliferation of cultivated
dermal fibroblasts was observed. To study the molecular mechanisms
resulting in the proliferative effect of pantothenate, gene expression
was analysed in dermal fibroblasts cultivated with 20 μg/ml of
pantothenate compared with untreated cells using the GeneChip® Human
Exon 1.0 ST Array. A number of significantly regulated genes were
identified including genes coding for interleukin (IL)-6, IL-8, Id1,
HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was
subsequently verified by quantitative real-time polymerase chain
reaction analysis. Induction of HMOX-1 expression by pantothenol
and pantothenic acid in dermal cells was confirmed on the protein
level using immunoblots. Functional studies revealed the enhanced
suppression of free radical formation in skin fibroblasts cultured
with panthenol. In conclusion, these studies provided new insight
in the molecular mechanisms linked to the stimulatory effect of pantothenate
and panthenol on the proliferation of dermal fibroblasts.},
issn = {1600-0625},
keywords = {dermal fibroblasts, gene expression profile, microarray analysis,
pantothenate, proliferation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-0625.2009.00884.x}
}
@ARTICLE{Wiederschain2007,
author = {Wiederschain, Dmitri and Chen, Lin and Johnson, Brett and Bettano,
Kimberly and Jackson, Dowdy and Taraszka, John and Wang, Y. Karen
and Jones, Michael D. and Morrissey, Michael and Deeds, James and
Mosher, Rebecca and Fordjour, Paul and Lengauer, Christoph and Benson,
John D.},
title = {Contribution of Polycomb Homologues Bmi-1 and Mel-18 to Medulloblastoma
Pathogenesis},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {4968--4979},
number = {13},
month = jul,
abstract = {Bmi-1 and Mel-18 are structural homologues that belong to the Polycomb
group of transcriptional regulators and are believed to stably maintain
repression of gene expression by altering the state of chromatin
at specific promoters. While a number of clinical and experimental
observations have implicated Bmi-1 in human tumorigenesis, the role
of Mel-18 in cancer cell growth has not been investigated. We report
here that short hairpin RNA-mediated knockdown of either Bmi-1 or
Mel-18 in human medulloblastoma DAOY cells results in the inhibition
of proliferation, loss of clonogenic survival, anchorage-independent
growth, and suppression of tumor formation in nude mice. Furthermore,
overexpression of both Bmi-1 and Mel-18 significantly increases the
clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation
of Bmi-1 or Mel-18 alone does not affect the growth of normal human
WI38 fibroblasts. Proteomics-based characterization of Bmi-1 and
Mel-18 protein complexes isolated from cancer cells revealed substantial
similarities in their respective compositions. Finally, gene expression
analysis identified a number of cancer-relevant pathways that may
be controlled by Bmi-1 and Mel-18 and also showed that these Polycomb
proteins regulate a set of common gene targets. Taken together, these
results suggest that Bmi-1 and Mel-18 may have overlapping functions
in cancer cell growth.},
url = {http://mcb.asm.org/cgi/content/abstract/27/13/4968}
}
@ARTICLE{Wieghaus2008,
author = {Wieghaus, Kristen A. and Gianchandani, Erwin P. and Paige, Mikell
A. and Brown, Milton L. and Botchwey, Edward A. and Papin, Jason
A.},
title = {Novel pathway compendium analysis elucidates mechanism of pro-angiogenic
synthetic small molecule},
journal = {Bioinformatics},
year = {2008},
volume = {24},
pages = {2384--2390},
number = {20},
month = oct,
abstract = {Motivation: Computational techniques have been applied to experimental
datasets to identify drug mode-of-action. A shortcoming of existing
approaches is the requirement of large reference databases of compound
expression profiles. Here, we developed a new pathway-based compendium
analysis that couples multi-timepoint, controlled microarray data
for a single compound with systems-based network analysis to elucidate
drug mechanism more efficiently. Results: We applied this approach
to a transcriptional regulatory footprint of phthalimide neovascular
factor 1 (PNF1)--a novel synthetic small molecule that exhibits significant
in vitro endothelial potency--spanning 1-48 h post-supplementation
in human micro-vascular endothelial cells (HMVEC) to comprehensively
interrogate PNF1 effects. We concluded that PNF1 first induces tumor
necrosis factor-alpha (TNF-{alpha}) signaling pathway function which
in turn affects transforming growth factor-beta (TGF-{beta}) signaling.
These results are consistent with our previous observations of PNF1-directed
TGF-{beta} signaling at 24 h, including differential regulation of
TGF-{beta}-induced matrix metalloproteinase 14 (MMP14/MT1-MMP) which
is implicated in angiogenesis. Ultimately, we illustrate how our
pathway-based compendium analysis more efficiently generates hypotheses
for compound mechanism than existing techniques. Availability: The
microarray data generated as part of this study are available in
the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/). Contact:
botchwey@virginia.edu; papin@virginia.edu Supplementary information:
Supplementary data are available at Bioinformatics online.},
url = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/20/2384}
}
@ARTICLE{Wienecke2010,
author = {Wienecke, J. and Westerdahl, A-C. and Hultborn, H. and Kiehn, O.
and Ryge, J.},
title = {Global Gene Expression Analysis of Rodent Motor Neurons Following
Spinal Cord Injury Associates Molecular Mechanisms With Development
of Postinjury Spasticity},
journal = {J Neurophysiol},
year = {2010},
volume = {103},
pages = {761--778},
number = {2},
month = feb,
abstract = {Spinal cord injury leads to severe problems involving impaired motor,
sensory, and autonomic functions. After spinal injury there is an
initial phase of hyporeflexia followed by hyperreflexia, often referred
to as spasticity. Previous studies have suggested a relationship
between the reappearance of endogenous plateau potentials in motor
neurons and the development of spasticity after spinalization. To
unravel the molecular mechanisms underlying the increased excitability
of motor neurons and the return of plateau potentials below a spinal
cord injury we investigated changes in gene expression in this cell
population. We adopted a rat tail-spasticity model with a caudal
spinal transection that causes a progressive development of spasticity
from its onset after 2 to 3 wk until 2 mo postinjury. Gene expression
changes of fluorescently identified tail motor neurons were studied
21 and 60 days postinjury. The motor neurons undergo substantial
transcriptional regulation in response to injury. The patterns of
differential expression show similarities at both time points, although
there are 20% more differentially expressed genes 60 days compared
with 21 days postinjury. The study identifies targets of regulation
relating to both ion channels and receptors implicated in the endogenous
expression of plateaux. The regulation of excitatory and inhibitory
signal transduction indicates a shift in the balance toward increased
excitability, where the glutamatergic N-methyl-D-aspartate receptor
complex together with cholinergic system is up-regulated and the
{gamma}-aminobutyric acid type A receptor system is down-regulated.
The genes of the pore-forming proteins Cav1.3 and Nav1.6 were not
up-regulated, whereas genes of proteins such as nonpore-forming subunits
and intracellular pathways known to modulate receptor and channel
trafficking, kinetics, and conductivity showed marked regulation.
On the basis of the identified changes in global gene expression
in motor neurons, the present investigation opens up for new potential
targets for treatment of motor dysfunction following spinal cord
injury.},
url = {http://jn.physiology.org/cgi/content/abstract/103/2/761}
}
@ARTICLE{Wiener2008,
author = {Wiener, Zoltan and Pocza, Peter and Racz, Melinda and Nagy, Gyorgy
and Tolgyesi, Gergely and Molnar, Viktor and Jaeger, Judit and Buzas,
Edit and Gorbe, Eva and Papp, Zoltan and Rigo, Janos and Falus, Andras},
title = {IL-18 induces a marked gene expression profile change and increased
Ccl1 (I-309) production in mouse mucosal mast cell homologs},
journal = {Int. Immunol.},
year = {2008},
volume = {20},
pages = {1565--1573},
number = {12},
month = dec,
abstract = {Helminthic infections, which are particularly common in the developing
world, are associated with the accumulation of mucosal mast cells
(MMCs) in the epithelial layer of the gut. Although intestinal parasite
infection models argue that IL-18 plays a role in MMC differentiation
and function, the direct effect of IL-18 on MMCs is still not well
understood. To clarify the role of IL-18 in mast cell biology, we
analyzed gene expression changes in MMCs in vitro. DNA microarray
technology uncovered a group of chemokines regulated by IL-18, among
which Ccl1 (I-309, TCA-3) showed the highest up-regulation. Ccl1
induction was only transient in mast cells and was characteristic
for both immature and mature MMCs, but not for connective tissue-type
mast cells. IL-18 exerts its Ccl1-inducing effect in MMCs primarily
via the activation of NF{kappa}B. Moreover, IL-18 was effective both
in the absence and the presence of IgE-antigen complex. The Ccl1
receptor (CCR8) is known to be expressed by Th2 cells and is involved
in their recruitment. Our present findings suggest that IL-18 may
contribute to mast cell-influenced Th2 responses by inducing Ccl1
production.},
url = {http://intimm.oxfordjournals.org/cgi/content/abstract/20/12/1565}
}
@ARTICLE{Wierinckx2007,
author = {Wierinckx, Anne and Auger, Carole and Devauchelle, Pauline and Reynaud,
Arlette and Chevallier, Pascale and Jan, Michel and Perrin, Gilles
and Fevre-Montange, Michelle and Rey, Catherine and Figarella-Branger,
Dominique and Raverot, Gerald and Belin, Marie-Francoise and Lachuer,
Joel and Trouillas, Jacqueline},
title = {A diagnostic marker set for invasion, proliferation, and aggressiveness
of prolactin pituitary tumors},
journal = {Endocr. Relat. Cancer},
year = {2007},
volume = {14},
pages = {887--900},
number = {3},
month = sep,
abstract = {Although most pituitary tumors are benign, some are invasive or aggressive.
In the absence of specific markers of malignancy, only tumors with
metastases are considered malignant. To identify markers of invasion
and aggressiveness, we focused on prolactin (PRL) tumors in the human
and rat. Using radiology and histological methods, we classified
25 human PRL tumors into three groups (non-invasive, invasive, and
aggressive-invasive) and compared them with a model of transplantable
rat PRL tumors with benign and malignant lineages. Combining histological(mitoses
and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG),
and polysialic acid neural cell adhesion molecule) and transcriptomic
(microarrays and q-RTPCR) methods with clinical data (post-surgical
outcome with case-control statistical analysis), we found nine genes
implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation
(PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation
(PITX1) showing differential expression in the three groups of tumors
(P = 0.015 to 0.0001). A case-control analysis, comparing patients
in remission (9 controls) and patients with persistent or recurrent
tumors (14 cases) revealed that eight out of the nine genes were
differentially up- or downregulated (P = 0.05 to 0.002), with only
PTTG showing no correlation with clinical course (P = 0.258). These
combined histological and transcriptomic analyses improve the pathological
diagnosis of PRL tumors, indicating a reliable procedure for predicting
tumor aggressiveness and recurrence potential. The similar gene profiles
found between non-invasive human and benign rat tumors, as well as
between aggressive-invasive human and malignant rat tumors provide
new insights into malignancy in human pituitary tumors.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/14/3/887}
}
@ARTICLE{Wierinckx2010,
author = {Wierinckx, Anne and Raverot, Gérald and Nazaret, Nicolas and Jouanneau,
Emmanuel and Auger, Carole and Lachuer, Joël and Trouillas, Jacqueline},
title = {Proliferation markers of human pituitary tumors: Contribution of
a genome-wide transcriptome approach},
journal = {Molecular and Cellular Endocrinology},
year = {2010},
volume = {326},
pages = {30--39},
number = {1-2},
month = sep,
abstract = {Predicting pituitary tumor behavior remains a challenge, since the
prognostic value of identified pathological markers has not yet been
evaluated. Genome-wide transcriptome analyses allow the identification
of molecular markers to highlight global changes in gene expression
and enable the discovery of signaling pathways within complex biological
networks. While several transcriptome studies comparing normal with
tumoral pituitary as a whole or with respect to subtype have given
interesting data concerning pituitary pathogenesis, none have considered
pituitary tumor prognosis. Only one study to date, focusing on the
pathological classification and progression of prolactin tumors,
has identified some molecular markers with diagnostic and prognostic
value. We reviewed data in the literature on human pituitary tumor
transcriptome and conducted a meta-analysis on the expression of
genes involved in cell growth, proliferation and the cell cycle.
Based on our expertise, we evaluate the interests and the limitations
of using this approach with human pituitary tumors.},
booktitle = {The Molecular Basis of Pituitary Tumorigenesis},
issn = {0303-7207},
keywords = {Pituitary tumors, Transcriptome, Molecular markers},
url = {http://www.sciencedirect.com/science/article/B6T3G-4YJ4NHW-2/2/20e3a9e59f38a630c6ffb2ba24aac86f}
}
@ARTICLE{Wierinckx2011,
author = {Wierinckx, Anne and Roche, Magali and Raverot, Gérald and Legras-Lachuer,
Catherine and Croze, Séverine and Nazaret, Nicolas and Rey, Catherine
and Auger, Carole and Jouanneau, Emmanuel and Chanson, Philippe and
Trouillas, Jacqueline and Lachuer, Joël},
title = {Integrated Genomic Profiling Identifies Loss of Chromosome 11p Impacting
Transcriptomic Activity in Aggressive Pituitary PRL Tumors},
journal = {Brain Pathology},
year = {2011},
volume = {21},
pages = {533--543},
number = {5},
abstract = {Integrative genomics approaches associating DNA structure and transcriptomic
analysis should allow the identification of cascades of events relating
to tumor aggressiveness. While different genome alterations have
been identified in pituitary tumors, none have ever been correlated
with the aggressiveness. This study focused on one subtype of pituitary
tumor, the prolactin (PRL) pituitary tumors, to identify molecular
events associated with the aggressive and malignant phenotypes. We
combined a comparative genomic hybridization and transcriptomic analysis
of 13 PRL tumors classified as nonaggressive or aggressive. Allelic
loss within the p arm region of chromosome 11 was detected in five
of the aggressive tumors. Allelic loss in the 11q arm was observed
in three of these five tumors, all three of which were considered
as malignant based on the occurrence of metastases. Comparison of
genomic and transcriptomic data showed that allelic loss impacted
upon the expression of genes located in the imbalanced region. Data
filtering allowed us to highlight five deregulated genes (DGKZ, CD44,
TSG101, GTF2H1, HTATIP2), within the missing 11p region, potentially
responsible for triggering the aggressive and malignant phenotypes
of PRL tumors. Our combined genomic and transcriptomic analysis underlines
the importance of chromosome allelic loss in determining the aggressiveness
and malignancy of tumors.},
doi = {10.1111/j.1750-3639.2011.00476.x},
issn = {1750-3639},
keywords = {aggressiveness of tumors, integrative genomics, loss of 11p, prolactinomas},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1750-3639.2011.00476.x}
}
@ARTICLE{Wiesner2010,
author = {Wiesner, Philipp and Choi, Soo-Ho and Almazan, Felicidad and Benner,
Christopher and Huang, Wendy and Diehl, Cody J. and Gonen, Ayelet
and Butler, Susan and Witztum, Joseph L. and Glass, Christopher K.
and Miller, Yury I.},
title = {Low Doses of Lipopolysaccharide and Minimally Oxidized Low-Density
Lipoprotein Cooperatively Activate Macrophages via Nuclear Factor
{kappa}B and Activator Protein-1: Possible Mechanism for Acceleration
of Atherosclerosis by Subclinical Endotoxemia},
journal = {Circ. Res.},
year = {2010},
volume = {107},
pages = {56--65},
number = {1},
month = jul,
abstract = {Rationale: Oxidized low-density lipoprotein (LDL) is an important
determinant of inflammation in atherosclerotic lesions. It has also
been documented that certain chronic infectious diseases, such as
periodontitis and chlamydial infection, exacerbate clinical manifestations
of atherosclerosis. In addition, low-level but persistent metabolic
endotoxemia is often found in diabetic and obese subjects and is
induced in mice fed a high-fat diet. Objective: In this study, we
examined cooperative macrophage activation by low levels of bacterial
lipopolysaccharide (LPS) and by minimally oxidized LDL (mmLDL), as
a model for subclinical endotoxemia-complicated atherosclerosis.
Methods and Results: We found that both in vitro and in vivo, mmLDL
and LPS (Kdo2-LipidA) cooperatively activated macrophages to express
proinflammatory cytokines Cxcl2 (MIP-2), Ccl3 (MIP-1{alpha}), and
Ccl4 (MIP-1{beta}). Importantly, the mmLDL and LPS cooperative effects
were evident at a threshold LPS concentration (1 ng/mL) at which
LPS alone induced only a limited macrophage response. Analyzing microarray
data with a de novo motif discovery algorithm, we found that genes
transcribed by promoters containing an activator protein (AP)-1 binding
site were significantly upregulated by costimulation with mmLDL and
LPS. In a nuclear factor-DNA binding assay, the cooperative effect
of mmLDL and LPS costimulation on c-Jun and c-Fos DNA binding, but
not on p65 or p50, was dependent on mmLDL-induced activation of extracellular
signal-regulated kinase (ERK) 1/2. In addition, mmLDL induced c-Jun
N-terminal kinase (JNK)-dependent derepression of AP-1 by removing
nuclear receptor corepressor (NCoR) from the chemokine promoters.
Conclusions: The cooperative engagement of AP-1 and nuclear factor
(NF)-{kappa}B by mmLDL and LPS may constitute a mechanism of increased
transcription of inflammatory cytokines within atherosclerotic lesions.},
url = {http://circres.ahajournals.org/cgi/content/abstract/107/1/56}
}
@ARTICLE{Wiggin2008,
author = {Wiggin, Timothy D. and Kretzler, Matthias and Pennathur, Subramaniam
and Sullivan, Kelli A. and Brosius, Frank C. and Feldman, Eva L.},
title = {Rosiglitazone Treatment Reduces Diabetic Neuropathy in Streptozotocin-Treated
DBA/2J Mice},
journal = {Endocrinology},
year = {2008},
volume = {149},
pages = {4928--4937},
number = {10},
month = oct,
abstract = {Diabetic neuropathy (DN) is a common complication of diabetes. Currently,
there is no drug treatment to prevent or slow the development of
DN. Rosiglitazone (Rosi) is a potent insulin sensitizer and may also
slow the development of DN by a mechanism independent of its effect
on hyperglycemia. A two by two design was used to test the effect
of Rosi treatment on the development of DN. Streptozotocin-induced
diabetic DBA/2J mice were treated with Rosi. DN and oxidative stress
were quantified, and gene expression was profiled using the Affymetrix
Mouse Genome 430 2.0 microarray platform. An informatics approach
identified key regulatory elements activated by Rosi. Diabetic DBA/2J
mice developed severe hyperglycemia, DN, and elevated oxidative stress.
Rosi treatment did not affect hyperglycemia but did reduce oxidative
stress and prevented the development of thermal hypoalgesia. Two
novel transcription factor binding modules were identified that may
control genes correlated to changes in DN after Rosi treatment: SP1F_ZBPF
and EGRF_EGRF. These targets may be useful in designing drugs with
the same efficacy as Rosi in treating DN but with fewer undesirable
effects.},
url = {http://endo.endojournals.org/cgi/content/abstract/149/10/4928}
}
@ARTICLE{Wigle2011,
author = {Tim J. Wigle and Sarah K. Knutson and Lei Jin and Kevin W. Kuntz
and Roy M. Pollock and Victoria M. Richon and Robert A. Copeland
and Margaret Porter Scott},
title = {The Y641C mutation of EZH2 alters substrate specificity for histone
H3 lysine 27 methylation states},
journal = {FEBS Letters},
year = {2011},
volume = {585},
pages = {3011 - 3014},
number = {19},
abstract = {Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET
domain of EZH2 have been identified in patients with certain subtypes
of non-Hodgkin lymphoma (NHL). These mutations were shown to change
the substrate specificity of EZH2 for various methylation states
of lysine 27 on histone H3 (H3K27). An additional mutation at EZH2
Y641 to cysteine (Y641C) was also found in one patient with NHL and
in SKM-1 cells derived from a patient with myelodisplastic syndrome
(MDS). The Y641C mutation has been reported to dramatically reduce
enzymatic activity. Here, we demonstrate that while the Y641C mutation
ablates enzymatic activity against unmethylated and monomethylated
H3K27, it is superior to wild-type in catalyzing the formation of
trimethylated H3K27 from the dimethylated precursor.},
doi = {10.1016/j.febslet.2011.08.018},
issn = {0014-5793},
keywords = {EZH2},
url = {http://www.sciencedirect.com/science/article/pii/S0014579311006089}
}
@ARTICLE{Wijchers2010,
author = {Wijchers, Patrick J. and Yandim, Cihangir and Panousopoulou, Eleni
and Ahmad, Mushfika and Harker, Nicky and Saveliev, Alexander and
Burgoyne, Paul S. and Festenstein, Richard},
title = {Sexual Dimorphism in Mammalian Autosomal Gene Regulation Is Determined
Not Only by Sry but by Sex Chromosome Complement As Well},
journal = {Developmental Cell},
year = {2010},
volume = {19},
pages = {477--484},
number = {3},
month = sep,
abstract = {Summary Differences between males and females are normally attributed
to developmental and hormonal differences between the sexes. Here,
we demonstrate differences between males and females in gene silencing
using a heterochromatin-sensitive reporter gene. Using "sex-reversal"
mouse models with varying sex chromosome complements, we found that
this differential gene silencing was determined by X chromosome complement,
rather than sex. Genome-wide transcription profiling showed that
the expression of hundreds of autosomal genes was also sensitive
to sex chromosome complement. These genome-wide analyses also uncovered
a role for Sry in modulating autosomal gene expression in a sex chromosome
complement-specific manner. The identification of this additional
layer in the establishment of sexual dimorphisms has implications
for understanding sexual dimorphisms in physiology and disease.PaperClip},
issn = {1534-5807},
url = {http://www.sciencedirect.com/science/article/B6WW3-51134T4-H/2/a83607044eccaa2ac73c771b002794d2}
}
@ARTICLE{Wiklund2011,
author = {Wiklund, Erik D. and Bramsen, Jesper B. and Hulf, Toby and Dyrskjøt,
Lars and Ramanathan, Ramshanker and Hansen, Thomas B. and Villadsen,
Sune B. and Gao, Shan and Ostenfeld, Marie S. and Borre, Michael
and Peter, Marcus E. and Ørntoft, Torben F. and Kjems, Jørgen and
Clark, Susan J.},
title = {Coordinated epigenetic repression of the miR-200 family and miR-205
in invasive bladder cancer},
journal = {International Journal of Cancer},
year = {2011},
volume = {128},
pages = {1327--1334},
number = {6},
abstract = {Abstract MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated
in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429)
and miR-205 are frequently silenced in advanced cancer and have been
implicated in epithelial to mesenchymal transition (EMT) and tumor
invasion by targeting the transcriptional repressors of E-cadherin,
ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription
in a negative feedback loop, but otherwise little is known about
the transcriptional regulation of the miR-200 family and miR-205.
Recently, miR-200 silencing was also reported in cancer stem cells,
implying that miR-200 deregulation is a key event in multiple levels
of tumor biology. However, what prevents miR-200 expression remains
largely unanswered. Here we report concerted transcriptional regulation
of the miR-200 and miR-205 loci in bladder tumors and bladder cell
lines. Using a combination of miRNA expression arrays, qPCR assays
and mass spectrometry DNA methylation analyses, we show that the
miR-200 and miR-205 loci are specifically silenced and gain promoter
hypermethylation and repressive chromatin marks in muscle invasive
bladder tumors and undifferentiated bladder cell lines. Moreover,
we report that miR-200c expression is significantly correlated with
early stage T1 bladder tumor progression, and propose miR-200 and
miR-205 silencing and DNA hypermethylation as possible prognostic
markers in bladder cancer. In addition, we observe that the mesoderm
transcription factor TWIST1 and miR-200 expression are inversely
correlated in bladder tumor samples and cell lines. TWIST1 associates
directly with the miR-200 and miR-205 promoters, and may act as a
repressor of miR-200 and miR-205 expression.},
doi = {10.1002/ijc.25461},
issn = {1097-0215},
keywords = {miR-200 family, miR-205, TWIST1, DNA methylation, epigenetics, bladder
cancer, tumor invasion},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25461}
}
@ARTICLE{Wilcox2007,
author = {Wilcox, Cathy and Feddes, Grace and Willett-Brozick, Joan and Hsu,
Lih-Ching and DeLoia, Julie and Baysal, Bora},
title = {Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes
in normal ovarian surface epithelial cells treated with progesterone:
implications for pathogenesis of ovarian cancer},
journal = {BMC Cancer},
year = {2007},
volume = {7},
pages = {223},
number = {1},
abstract = {BACKGROUND:Ovarian cancer (OvCa) most often derives from ovarian surface
epithelial (OSE) cells. Several lines of evidence strongly suggest
that increased exposure to progesterone (P4) protects women against
developing OvCa. However, the underlying mechanisms of this protection
are incompletely understood.METHODS:To determine downstream gene
targets of P4, we established short term in vitro cultures of non-neoplastic
OSE cells from six subjects, exposed the cells to P4 (10-6 M) for
five days and performed transcriptional profiling with oligonucleotide
microarrays containing over 22,000 transcripts.RESULTS:We identified
concordant but modest gene expression changes in cholesterol/lipid
homeostasis genes in three of six samples (responders), whereas the
other three samples (non-responders) showed no expressional response
to P4. The most up-regulated gene was TMEM97 which encodes a transmembrane
protein of unknown function (MAC30). Analyses of outlier transcripts,
whose expression levels changed most significantly upon P4 exposure,
uncovered coordinate up-regulation of 14 cholesterol biosynthesis
enzymes, insulin-induced gene 1, low density lipoprotein receptor,
ABCG1, endothelial lipase, stearoyl- CoA and fatty acid desaturases,
long-chain fatty-acyl elongase, and down-regulation of steroidogenic
acute regulatory protein and ABCC6. Highly correlated tissue-specific
expression patterns of TMEM97 and the cholesterol biosynthesis genes
were confirmed by analysis of the GNF Atlas 2 universal gene expression
database. Real-time quantitative RT-PCR analyses revealed 2.4-fold
suppression of the TMEM97 gene expression in short-term cultures
of OvCa relative to the normal OSE cells.CONCLUSION:These findings
suggest that a co-regulated transcript network of cholesterol/lipid
homeostasis genes and TMEM97 are downstream targets of P4 in normal
OSE cells and that TMEM97 plays a role in cholesterol and lipid metabolism.
The P4-induced alterations in cholesterol and lipid metabolism in
OSE cells might play a role in conferring protection against OvCa.},
doi = {10.1186/1471-2407-7-223},
issn = {1471-2407},
owner = {Meike Kuschel},
pubmedid = {18070364},
timestamp = {2010.04.07},
url = {http://www.biomedcentral.com/1471-2407/7/223}
}
@ARTICLE{Wilde2010,
author = {de Wilde, Janneke and Hulshof, Martijn and Boekschoten, Mark and
de Groot, Philip and Smit, Egbert and Mariman, Edwin},
title = {The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types
in a diet-independent and fiber-type unrelated way},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {176},
number = {1},
abstract = {BACKGROUND:The mouse skeletal muscle is composed of four distinct
fiber types that differ in contractile function, number of mitochondria
and metabolism. Every muscle type has a specific composition and
distribution of the four fiber types. To find novel genes involved
in specifying muscle types, we used microarray analysis to compare
the gastrocnemius with the quadriceps from mice fed a low fat diet
(LFD) or high fat diet (HFD) for 8 weeks. Additional qPCR analysis
were performed in the gastrocnemius, quadriceps and soleus muscle
from mice fed an LFD or HFD for 20 weeks.RESULTS:In mice fed the
8-week LFD 162 genes were differentially expressed in the gastrocnemius
vs. the quadriceps. Genes with the strongest differences in expression
were markers for oxidative fiber types (e.g. Tnni1) and genes which
are known to be involved in embryogenesis (Dkk3, Hoxd8,Hoxd9 and
Tbx1). Also Dkk2, Hoxa5, Hoxa10, Hoxc9, Hoxc10, Hoxc6 and Tbx15 were
detectably, but not differentially expressed in adult muscle tissue.
Expression of differentially expressed genes was not influenced by
an 8-week or 20-week HFD. Comparing gastrocnemius, quadriceps and
soleus, expression of Hoxd8 and Hoxd9 was not related with expression
of markers for the four different fiber types. We found that the
expression of both Hoxd8 and Hoxd9 was much higher in the gastrocnemius
than in the quadriceps or soleus, whereas the expression of Dkk3
was high in quadriceps, but low in both gastrocnemius and soleus.
Finally, expression of Tbx1 was high in quadriceps, intermediate
in soleus and low in gastrocnemius.CONCLUSIONS:We found that genes
from the Dkk family, Hox family and Tbx family are detectably expressed
in adult mouse muscle. Interestingly, expression of Dkk3, Hoxd8,
Hoxd9 and Tbx1 was highly different between gastrocnemius, quadriceps
and soleus. In fact, every muscle type showed a unique combination
of expression of these four genes which was not influenced by diet.
Altogether, we conclude that genes important for embryogenesis identify
mouse muscle types in a diet-independent and fiber type-unrelated
manner.},
doi = {10.1186/1471-2164-11-176},
issn = {1471-2164},
pubmedid = {20230627},
url = {http://www.biomedcentral.com/1471-2164/11/176}
}
@ARTICLE{Wilde2008,
author = {de Wilde, Janneke and Mohren, Ronny and van den Berg, Sjoerd and
Boekschoten, Mark and Dijk, Ko Willems-Van and de Groot, Philip and
Muller, Michael and Mariman, Edwin and Smit, Egbert},
title = {Short-term high fat-feeding results in morphological and metabolic
adaptations in the skeletal muscle of C57BL/6J mice},
journal = {Physiol Genomics},
year = {2008},
volume = {32},
pages = {360--369},
number = {3},
month = feb,
abstract = {The prevalence of the metabolic syndrome (MS) is rapidly increasing
all over the world. Consequently, there is an urgent need for more
effective intervention strategies. Both animal and human studies
indicate that lipid oversupply to skeletal muscle can result in insulin
resistance, which is one of the characteristics of the MS. C57BL/6J
mice were fed a low-fat (10 kcal%) palm oil diet or a high-fat (45
kcal%; HF) palm oil diet for 3 or 28 days. By combining transcriptomics
with protein and lipid analyses we aimed to better understand the
molecular events underlying the early onset of the MS. Short-term
HF feeding led to altered expression levels of genes involved in
a variety of biological processes including morphogenesis, energy
metabolism, lipogenesis, and immune function. Protein analysis showed
increased levels of the myosin heavy chain, slow fiber type protein,
and the complexes I, II, III, IV, and V of the oxidative phosphorylation.
Furthermore, we observed that the main mitochondrial membrane phospholipids,
phosphatidylcholine and phosphatidylethanolamine, contained more
saturated fatty acids. Altogether, these results point to a morphological
as well as a metabolic adaptation by promoting a more oxidative fiber
type. We hypothesize that after this early positive adaptation, a
continued transcriptional downregulation of genes involved in oxidative
phosphorylation will result in decreased oxidative capacity at a
later stage. Together with increased saturation of phospholipids
of the mitochondrial membrane this can result in decreased mitochondrial
function, which is a hallmark observed in insulin resistance and
Type 2 diabetes.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/32/3/360}
}
@ARTICLE{Wilde2008a,
author = {de Wilde, Jillian and Wilting, Saskia M. and Meijer, Chris J.L.M.
and van de Wiel, Mark A. and Ylstra, Bauke and Snijders, Peter J.F.
and Steenbergen, Renske D.M.},
title = {Gene expression profiling to identify markers associated with deregulated
hTERT in HPV-transformed keratinocytes and cervical cancer},
journal = {Int. J. Cancer},
year = {2008},
volume = {122},
pages = {877--888},
number = {4},
abstract = {Abstract 10.1002/ijc.23210.abs Although high-risk human papillomavirus
(HPV) infection plays a major role in the development of cervical
cancer, additive oncogenic events are involved as well. One key event
involves increased activity of telomerase resulting from a deregulated
expression of its catalytic subunit hTERT. Our previous microcell-mediated
chromosome transfer studies revealed that introduction of human chromosome
6 in the HPV16-immortalized keratinocyte cell line FK16A and in the
HPV16-containing cervical cancer cell line SiHa induced growth arrest,
resulting from a repression of hTERT mRNA expression and telomerase
activity. Here, this model was used to analyze expression profiles
associated with hTERT deregulation in HPV-transformed cells. Microarray
expression analysis of 12 FK16A/chromosome 6 hybrids, 4 of which
were negative for endogenous hTERT and 8 of which were positive for
endogenous hTERT, resulted in the identification of 164 differentially
expressed genes. Differential expression of a selection of 5 genes
was verified by real-time RT-PCR. Of these 164 genes, 32 were also
differentially expressed in other HPV transformed cells with deregulated
hTERT. For 2 of these genes, encoding AQP3 and MGP, altered expression
in hTERT positive cervical carcinomas was confirmed by real-time
RT-PCR and immunohistochemistry, respectively. Moreover, increased
MGP protein expression was significantly more frequent in high-grade
cervical premalignant lesions with elevated hTERT mRNA expression
compared to those without. In summary, we identified 32 candidate
biomarkers for deregulated hTERT mRNA expression, which may enable
the identification of cervical premalignant lesions that are at highest
risk to progress to invasive cancer. © 2007 Wiley-Liss, Inc.},
issn = {1097-0215},
keywords = {HPV, hTERT, telomerase, cervical carcinogenesis, microarray expression
analysis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.23210}
}
@ARTICLE{Wildenberg2008,
author = {Wildenberg, Manon E. and van Helden-Meeuwsen, Cornelia G. and
van de Merwe, Joop P. and Drexhage, Hemmo A. and Versnel, Marjan A.},
title = {Systemic increase in type I interferon activity in Sjögren's syndrome:
A putative role for plasmacytoid dendritic cells},
journal = {Eur. J. Immunol.},
year = {2008},
volume = {38},
pages = {2024--2033},
number = {7},
abstract = {Abstract 10.1002/eji.200738008.abs In the salivary glands of primary
Sjögren's syndrome (pSjS) patients, type I IFN activity is increased,
but systemic levels of type I IFN proteins are rarely detected.
This study focused on the systemic activity of type I IFN in pSjS,
as well as the role of peripheral plasmacytoid dendritic cells (pDC).
Monocytes obtained from pSjS patients showed an increased expression
of 40 genes. Twenty-three of these genes (58%), including IFI27,
IFITM1, IFIT3 and IFI44, were inducible by type I IFN. pSjS serum
had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44
in the monocytic cell line THP-1, likely due to the action of IFN-β.
This effect could be inhibited by blocking the type I IFN receptor,
supporting a high type I IFN bioactivity in pSjS serum. In addition,
circulatory pDC showed increased expression of CD40. This expression
was correlated to the expression level of the type I IFN-regulated
genes IFI27 and IFITM1 in monocytes of the same individual. This
study indicates that the increased type I IFN activity observed
in pSjS patients is not only a local but also a systemic phenomenon
and points to pDC as a possible source of this activity.},
issn = {1521-4141},
keywords = {Plasmacytoid DC, Sjögren's syndrome, Type I interferon},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200738008}
}
@ARTICLE{Wilf2011,
author = {Wilf, Nabil M. and Williamson, Neil R. and Ramsay, Joshua P. and
Poulter, Simon and Bandyra, Kasia J. and Salmond, George P. C.},
title = {The RNA chaperone, Hfq, controls two luxR-type regulators and plays
a key role in pathogenesis and production of antibiotics in Serratia
sp. ATCC 39006},
journal = {Environmental Microbiology},
year = {2011},
volume = {13},
pages = {2649--2666},
number = {10},
abstract = {Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that
is virulent in plant (potato) and animal (Caenorhabditis elegans)
models. It produces two secondary metabolite antibiotics, a prodigiosin
and a carbapenem, and the exoenzymes, pectate lyase and cellulase.
A complex regulatory network that includes quorum sensing (QS) controls
production of prodigiosin. While many aspects of the regulation of
the metabolites and exoenzymes are well understood, the potential
role in this network of the RNA chaperone Hfq and dependent small
regulatory RNAs has not been characterized. Hfq is an RNA chaperone
involved in post-transcriptional regulation that plays a key role
in stress response and virulence in diverse bacterial species. To
explore whether Hfq-dependent processes might contribute to the regulation
of antibiotic production we constructed an S39006 Δhfq mutant. Production
of prodigiosin and carbapenem was abolished in this mutant strain,
while production of the QS signalling molecule, butanoyl homoserine
lactone (BHL), was unaffected. Using transcriptional fusions, we
found that Hfq regulates the QS response regulators, SmaR and CarR.
Additionally, exoenzyme production and swimming motility were decreased
in a Δhfq mutant, and virulence was attenuated in potato and C. elegans
models. These results suggest that an Hfq-dependent pathway is involved
in the regulation of virulence and secondary metabolite production
in S39006.},
doi = {10.1111/j.1462-2920.2011.02532.x},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2011.02532.x}
}
@ARTICLE{Wilflingseder2010,
author = {Wilflingseder, Julia and Kainz, Alexander and Mühlberger, Irmgard
and Perco, Paul and Langer, Robert and Kristo, Ivan and Mayer, Bernd
and Oberbauer, Rainer},
title = {Impaired metabolism in donor kidney grafts after steroid pretreatment},
journal = {Transplant International},
year = {2010},
volume = {23},
pages = {796--804},
number = {8},
abstract = {Summary We recently showed in a randomized control trial that steroid
pretreatment of the deceased organ donor suppressed inflammation
in the transplant organ but did not reduce the rate or duration of
delayed graft function (DGF). This study sought to elucidate such
of those factors that caused DGF in the steroid-treated subjects.
Genome-wide gene expression profiles were used from 20 steroid-pretreated
donor-organs and were analyzed on the level of regulatory protein–protein
interaction networks. Significance analysis of microarrays (SAM)
yielded 63 significantly down-regulated sequences associated with
DGF that could be functionally categorized according to Protein ANalysis
THrough Evolutionary Relationships ontologies into two main biologic
processes: transport (PÂ <Â 0.001) and metabolism (PÂ <Â 0.001).
The identified genes suggest hypoxia as the cause of DGF, which cannot
be counterbalanced by steroid treatment. Our data showed that molecular
pathways affected by ischemia such as transport and metabolism are
associated with DGF. Potential interventional targeted therapy based
on these findings includes peroxisome proliferator-activated receptor
agonists or caspase inhibitors.},
issn = {1432-2277},
keywords = {bioinformatics, delayed graft function, renal transplantation, system
biology, transcriptome},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1432-2277.2010.01053.x}
}
@ARTICLE{Wilflingseder2009,
author = {Wilflingseder, Julia and Kainz, Alexander and Perco, Paul and Korbely,
Reka and Mayer, Bernd and Oberbauer, Rainer},
title = {Molecular predictors for anaemia after kidney transplantation},
journal = {Nephrol. Dial. Transplant.},
year = {2009},
volume = {24},
pages = {1015--1023},
number = {3},
month = mar,
abstract = {Background. Anaemia of chronic kidney disease is a well-studied comorbidity,
but the molecular predictors of post-transplant anaemia remain elusive.
Methods. In this case-control study, 25 subjects with post-transplant
anaemia, defined as erythropoiesis-stimulating agent (ESA) requirement
within the first post-transplant year, were matched to 25 control
recipients with comparable demographics but no anaemia using the
Austrian Dialysis and Transplant Registry. Genome-wide gene expression
analyses of deceased donor kidney biopsies obtained immediately before
engraftment were performed using custom cDNA microarrays. Significant
molecular features were included together with clinical variables
in a multivariable logistic regression analysis and further analysed
with respect to their molecular functions, biological processes and
cellular locations using gene ontology terms and protein-protein
interactions. Results. Immunity response molecules were over-represented
in the up-regulated gene list suggesting the involvement of the inflammation
cascade as a predictor of ESA requirement after engraftment. From
the initial list of the 34 differentially expressed genes, we identified
the best three genes predicting ESA requirement in the first year
by a stepwise gene selection algorithm. SPRR2C (OR = 0.24, 95% CI
0.07-0.85, P = 0.027) and GSTT1 (OR = 2.40, 95% CI 1.21-4.77, P =
0.013) remained significant after adjusting for donor age, eGFR,
BCAR and CRP. Conclusion. In summary, we identified three biomarkers
(SPRR2C, B3GALTL and GSTT1) of post-transplant anaemia in donor kidney
biopsies that correctly predicted ESA requirement within the first
year after transplantation in 93% of the cases.},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/24/3/1015}
}
@ARTICLE{Wilflingseder2008,
author = {Wilflingseder, J. and Perco, P. and Kainz, A. and Korbély, R. and
Mayer, B. and Oberbauer, R.},
title = {Biocompatibility of haemodialysis membranes determined by gene expression
of human leucocytes: a crossover study},
journal = {European Journal of Clinical Investigation},
year = {2008},
volume = {38},
pages = {918--924},
number = {12},
abstract = {ABSTRACT Background  Biocompatibility of haemodialysis membranes
is the most important quality criteria to enable long-term dialysis
without major harmful effects. This study sought to evaluate the
differences of genomic signatures derived from peripheral blood mononuclear
cells (PBMC) in patients undergoing haemodialysis treatment using
two different dialyser membranes: one semi-synthetic and one full-synthetic
membrane. Design  Microarray experiments were conducted in PBMCs
of four stable haemodialysis patients before and after dialysis comparing
semi-synthetic (Hemophan® GFS Plus 16) and full-synthetic (Hemoflow®
FX80) dialysis membranes, respectively. Genes differentially expressed
when comparing the two different membranes used were analysed in
order to elucidate the underlying molecular mechanisms affecting
PBMCs in the course of dialysis treatment. Results  One hundred
and seventy-two genes were identified as up-regulated after treatment
with semi-synthetic membranes when compared to full-synthetic membranes.
These genes could be assigned to processes including immunity and
defence, signal transduction, and apoptosis. Dialysis with a full-synthetic
membrane, on the other hand, led to an activation of 72 genes that
were mainly involved in cell cycle and cell cycle control. Conclusion 
The over-representation of genes belonging to immunity/defence, signal
transduction, and apoptosis as found with semi-synthetic membranes
suggests that full-synthetic membranes are more biocompatible than
semi-synthetic membranes.},
issn = {1365-2362},
keywords = { Biocompatibility, gene expression, haemodialysis membranes, microarrays,
peripheral blood mononuclear cell},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2362.2008.02050.x}
}
@ARTICLE{Wilhelm2012,
author = {A. Wilhelm and F. Jahns and S. Böcker and H. Mothes and K.O. Greulich
and M. Glei},
title = {Culturing explanted colon crypts highly improves viability of primary
non-transformed human colon epithelial cells},
journal = {Toxicology in Vitro},
year = {2012},
volume = {26},
pages = {133 - 141},
number = {1},
abstract = {Chemoprotective effects of nutritional compounds are usually studied
in cell lines. Studies using primary human colon cells have been
limited due to the lack of established methods regarding their culture.
We therefore optimized isolation and culture of non-transformed human
epithelial cells from individual donors to enrich viable cells and
sufficient amounts of intact RNA. Isolated epithelial cells were
seeded in different coated cell culture dishes combined with several
media (2–24 h). To avoid cells from anoikis, also intact colon
crypts were isolated to maintain cell interactions. These crypts
were incubated with gut fermentation products (24 h) derived
from indigestible carbohydrates. In none of the coated (fibronectin,
laminin) cell culture dishes isolated epithelial cells did attach.
The number of these cells remaining in suspension, decreased already
after 2 h to 20%. Intact colon crypts cultured as pellets showed
a stable viability up to 24 h (91 ± 4%) and were
suitable to gain a sufficient quantity of RNA. The use of colon crypts
with an appropriate cell culture medium could double the lifespan
of intestinal epithelial cells from 12 up to 24 h and represents
a promising approach to study early events in carcinogenesis and
chemoprevention as well as other diseases of the colon.},
doi = {10.1016/j.tiv.2011.10.008},
issn = {0887-2333},
keywords = {Human colon epithelial cells},
url = {http://www.sciencedirect.com/science/article/pii/S0887233311002748}
}
@ARTICLE{Wilhelm2011,
author = {Wilhelm, Brian T. and Briau, Mathieu and Austin, Pamela and Faubert,
Amelie and Boucher, Genevieve and Chagnon, Pierre and Hope, Kristin
and Girard, Simon and Mayotte, Nadine and Landry, Josette-Renee and
Hebert, Josee and Sauvageau, Guy},
title = {RNA-seq analysis of 2 closely related leukemia clones that differ
in their self-renewal capacity},
journal = {Blood},
year = {2011},
volume = {117},
pages = {e27--38},
number = {2},
month = jan,
abstract = {The molecular mechanisms regulating self-renewal of leukemia stem
cells remain poorly understood. Here we report the generation of
2 closely related leukemias created through the retroviral overexpression
of Meis1 and Hoxa9. Despite their apparent common origin, these clonal
leukemias exhibit enormous differences in stem cell frequency (from
1 in 1.4, FLA2; to 1 in 347, FLB1), suggesting that one of these
leukemias undergoes nearly unlimited self-renewal divisions. Using
next-generation RNA-sequencing, we characterized the transcriptomes
of these phenotypically similar, but biologically distinct, leukemias,
identifying hundreds of differentially expressed genes and a large
number of structural differences (eg, alternative splicing and promoter
usage). Focusing on ligand-receptor pairs, we observed high expression
levels of Sdf1-Cxcr4; Jagged2-Notch2/1; Osm-Gp130; Scf-cKit; and
Bmp15-Tgfb1/2. Interestingly, the integrin beta 2-like gene (Itgb2l)
is both highly expressed and differentially expressed between our
2 leukemias ([~] 14-fold higher in FLA2 than FLB1). In addition,
gene ontology analysis indicated G-protein-coupled receptor had a
much higher proportion of differential expression (22%) compared
with other classes ([~] 5%), suggesting a potential role regulating
subtle changes in cellular behavior. These results provide the first
comprehensive transcriptome analysis of a leukemia stem cell and
document an unexpected level of transcriptome variation between phenotypically
similar leukemic cells.},
comment = {10.1182/blood-2010-07-293332},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/2/e27}
}
@ARTICLE{Wilhelm2010,
author = {Wilhelm, Emmanuelle and Kornete, Mara and Targat, Brice and Vigneault-Edwards,
Jimmy and Frontini, Mattia and Tora, Laszlo and Benecke, Arndt and
Bell, Brendan},
title = {TAF6d orchestrates an apoptotic transcriptome profile and interacts
functionally with p53},
journal = {BMC Molecular Biology},
year = {2010},
volume = {11},
pages = {10},
number = {1},
abstract = {BACKGROUND:TFIID is a multiprotein complex that plays a pivotal role
in the regulation of RNA polymerase II (Pol II) transcription owing
to its core promoter recognition and co-activator functions. TAF6
is a core TFIID subunit whose splice variants include the major TAF6a
isoform that is ubiquitously expressed, and the inducible TAF6d.
In contrast to TAF6a, TAF6d is a pro-apoptotic isoform with a 10
amino acid deletion in its histone fold domain that abolishes its
interaction with TAF9. TAF6d expression can dictate life versus death
decisions of human cells.RESULTS:Here we define the impact of endogenous
TAF6d expression on the global transcriptome landscape. TAF6d was
found to orchestrate a transcription profile that included statistically
significant enrichment of genes of apoptotic function. Interestingly,
gene expression patterns controlled by TAF6d share similarities with,
but are not equivalent to, those reported to change following TAF9
and/or TAF9b depletion. Finally, because TAF6d regulates certain
p53 target genes, we tested and demonstrated a physical and functional
interaction between TAF6d and p53.CONCLUSION:Together our data define
a TAF6d-driven apoptotic gene expression program and show crosstalk
between the p53 and TAF6d pathways.},
doi = {10.1186/1471-2199-11-10},
issn = {1471-2199},
pubmedid = {20096117},
url = {http://www.biomedcentral.com/1471-2199/11/10}
}
@ARTICLE{Wilhelm2006,
author = {Wilhelm, Jochen and Muyal, Jai Prakash and Best, Johannes and Kwapiszewska,
Grazyna and Stein, Maria Magdalena and Seeger, Werner and Bohle,
Rainer Maria and Fink, Ludger},
title = {Systematic Comparison of the T7-IVT and SMART-Based RNA Preamplification
Techniques for DNA Microarray Experiments},
journal = {Clin. Chem.},
year = {2006},
volume = {52},
pages = {1161--1167},
number = {6},
month = jun,
abstract = {Background: Small biological samples obtained from biopsies or laser
microdissection often do not yield sufficient RNA for successful
microarray hybridization; therefore, RNA amplification is performed
before microarray experiments. We compared 2 commonly used techniques
for RNA amplification. Methods: We compared 2 commercially available
methods, Arcturus RiboAmp for in vitro transcription (IVT) and Clontech
BD SMARTTM for PCR, to preamplify 50 ng of total RNA isolated from
mouse livers and kidneys. Amplification factors of 3 sequences were
determined by real-time PCR. Differential expression profiles were
compared within and between techniques as well as with unamplified
samples with 10K 50mer oligomer-spotted microarrays (MWG Biotech).
The microarray results were validated on the transcript and protein
levels by comparison with public expression databases. Results: Amplification
factors for specific sequences were lower after 2 rounds of IVT than
after 12 cycles of SMART. Furthermore, IVT showed a clear decrease
in amplification with increasing distance of the amplified sequences
from the polyA tail, indicating generation of smaller products. In
the microarray experiments, reproducibility of the duplicates was
highest after SMART. In addition, SMART-processed samples showed
higher correlation when compared with unamplified samples as well
as with expression databases. Conclusions: Whenever 1 round of T7-IVT
does not yield sufficient product for microarray hybridization, which
is usually the case when <200 ng of total RNA is used as starting
material, we suggest the use of SMART PCR for preamplification.},
url = {http://www.clinchem.org/cgi/content/abstract/52/6/1161}
}
@ARTICLE{Wilhide2011,
author = {Wilhide, Michael E. and Tranter, Michael and Ren, Xiaoping and Chen,
Jing and Sartor, Maureen A. and Medvedovic, Mario and Jones, W. Keith},
title = {Identification of a NF-[kappa]B cardioprotective gene program: NF-[kappa]B
regulation of Hsp70.1 contributes to cardioprotection after permanent
coronary occlusion},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2011},
volume = {51},
pages = {82-89},
abstract = {The transcription factor Nuclear Factor Kappa B (NF-[kappa]B) has
been shown to be cardioprotective after permanent coronary occlusion
(PO) and late ischemic preconditioning (IPC), and yet it is cell
injurious after ischemia/reperfusion (I/R) in the heart. There is
limited information regarding NF-[kappa]B-dependent cardioprotection,
and the NF-[kappa]B-dependent genes that contribute to the cardioprotection
after PO are completely unknown. The objective of the study was to
identify NF-[kappa]B-dependent genes that contribute to cardioprotection
after PO. Microarray analysis was used to delineate genes that potentially
contribute to the NF-[kappa]B-dependent cardioprotection by determining
the overlap between the set of PO regulated genes and genes regulated
by NF-[kappa]B, using mice with genetic abrogation of NF-[kappa]B
activation in the heart. This analysis identified 16 genes as candidates
for NF-[kappa]B-dependent effects after PO. This set of genes overlaps
with, but is significantly different from the set of genes we previously
identified as regulated by NF-[kappa]B after IPC. The genes encoding
heat shock protein 70.3 (hspa1a) and heat shock protein 70.1 (hspa1b)
were the most significantly regulated genes after PO and were up-regulated
by NF-[kappa]B. Results using knockout mice show that Hsp70.1 contributes
to NF-[kappa]B-dependent cardioprotection after PO and likely underlies,
at least in part, the NF-[kappa][Beta]-dependent cardioprotective
effect. Our previous results show that Hsp70.1 is injurious after
I/R injury. This demonstrates that, like NF-[kappa]B itself, Hsp70.1
has antithetical effects on myocardial survival and suggests that
this may underlie the similar antithetical effects of NF-[kappa]B
after different ischemic stimuli. The significance of the research
is that understanding the gene network regulated by NF-[kappa]B after
ischemic insult may lead to identification of therapeutic targets
more appropriate for clinical development.},
issn = {0022-2828},
keywords = {Nuclear factor kappa B (NF-[kappa]B), Heat shock protein 70 (Hsp70),
Permanent coronary occlusion (PO), Myocardial infarction (MI), Microarray,
Gene expression, Cardioprotection},
url = {http://www.sciencedirect.com/science/article/pii/S0022282811001234}
}
@ARTICLE{Wilk2011,
author = {Wilk, Sabrina and Scheibenbogen, Carmen and Bauer, Sandra and Jenke,
Alexander and Rother, Madlen and Guerreiro, Manuel and Kudernatsch,
Robert and Goerner, Nicole and Poller, Wolfgang and Elligsen-Merkel,
Diana and Utku, Nalan and Magrane, Jordi and Volk, Hans D. and Skurk,
Carsten},
title = {Adiponectin is a negative regulator of antigen-activated T cells},
journal = {European Journal of Immunology},
year = {2011},
volume = {41},
pages = {2323--2332},
number = {8},
abstract = {Adiponectin (APN), a cytokine constitutively produced in fat tissue,
has been shown to exert anti-inflammatory effects in various disease
models. While the influence of APN on monocytic cells has been extensively
studied in vitro, little is known about its role in T cells. In this
study, we show that while <10% of human peripheral blood T cells
express adiponectin receptors (AdipoRs) on their surface, most T
cells store AdipoRs in intracellular compartments. AdipoRs colocalized
with immune regulatory molecules CTLA-4 and TIRC7 within clathrin-coated
vesicles. After stimulation, the expression of adiponectin receptor
1 (AdipoR1) and AdipoR2 was upregulated on the surface of antigen-specific
T cells, as determined by tetramer or CD137 staining, and AdipoR1
and AdipoR2 coexpressed with CTLA-4. Addition of APN resulted in
a significant diminution of antigen-specific T-cell expansion. Mechanistically,
APN enhanced apoptosis and inhibited proliferation of antigen-specific
T-cell lines. Further, APN directly inhibited cytokine production
in response to antigen stimulation. In line with the in vitro data,
APN-deficient (knockout, KO) mice had higher frequencies of CD137+
T cells upon Coxsackie B virus infection. Altogether, our data suggest
that APN is a novel negative T-cell regulator. In contrast to the
CTLA-4 ligand B7 only expressed on APCs, APN is abundant in human
plasma.},
doi = {10.1002/eji.201041349},
issn = {1521-4141},
keywords = {Adiponectin, Adiponectin receptors, Immunomodulation, T cells},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.201041349}
}
@ARTICLE{Wilke2010,
author = {Wilke, Gordon and Steinhauser, Gudrun and Grün, Joachim and Berek,
Claudia},
title = {In silico subtraction approach reveals a close lineage relationship
between follicular dendritic cells and BP3hi stromal cells isolated
from SCID mice},
journal = {Eur. J. Immunol.},
year = {2010},
volume = {40},
pages = {2165--2173},
number = {8},
abstract = {Abstract 10.1002/eji.200940202.abs Organization of the stromal compartments
in secondary lymphoid tissue is a prerequisite for an efficient immune
reaction. In particular, follicular dendritic cells (FDC) are pivotal
for the activation and differentiation of B cells. To investigate
the development of FDC, FDC together with tightly associated B cells
(FDC networks) were micro-dissected from frozen tissue sections and
follicular B cells were sorted by FACS. Using an in silico subtraction
approach, gene expression of FDC was determined and compared with
that of follicular stromal cells micro-dissected from the spleen
of SCID mice. Nearly 90% of the FDC genes were expressed in follicular
stromal cells of the SCID mouse, providing further evidence that
FDC develop from the residual network of reticular cells. Thus, it
suggests that rather minor modifications in the gene expression profile
are sufficient for differentiation into mature FDC. The analysis
of different immune-deficient mouse strains shows that a complex
pattern of gene regulation controls the development of residual stromal
cells into mature FDC. The in silico subtraction approach provides
a molecular framework within which to determine the diverse roles
of FDC in support of B cells and to investigate the differentiation
of FDC from their mesenchymal precursor cells.},
issn = {1521-4141},
keywords = {Differentiation, Follicular dendritic cell, Gene expression, Stromal
cell},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/eji.200940202}
}
@ARTICLE{Wilke2003,
author = {Wilke, Russell A. and Kolbert, Christopher P. and Rahimi, Rod A.
and Windebank, Anthony J.},
title = {Methylmercury Induces Apoptosis in Cultured Rat Dorsal Root Ganglion
Neurons},
journal = {NeuroToxicology},
year = {2003},
volume = {24},
pages = {369--378},
number = {3},
month = jun,
abstract = {Methylmercury is known to have devastating effects on the mammalian
nervous system. In order to characterize the dose dependence of methylmercury-induced
neurotoxicity, we first studied neurite outgrowth from rat dorsal
root ganglia explants. In this model, methylmercury inhibited neurite
outgrowth with a TD50 of approximately 0.5 [mu]M. We then used this
relationship to optimize dosing for subsequent transcriptional profiling
analyses in two independent neuronal model systems: dissociated sensory
neurons and PC12 cells. As seen in previous studies, the expression
of a number of genes associated with oxidative stress was altered
following a 6 h challenge with 1 [mu]M methylmercury. When PC12 cells
were subjected to a longer exposure (24 h), a relative increase was
noted in the representation of genes associated with cell cycling
and apoptosis. To confirm the presence of apoptosis in cultured neurons,
we then applied TUNEL staining and bis-benzimide staining techniques
to primary cultures of dissociated sensory neurons. After 24 h, 1 [mu]M
methylmercury increased both DNA end-labeling (P<0.01) and nuclear
fragmentation (P<0.02). The latter effect appeared to be dose-dependent.},
issn = {0161-813X},
keywords = {Methylmercury, Mercury, Oxidative stress, Microarray, Neurons},
url = {http://www.sciencedirect.com/science/article/B6W81-48H84MP-2/2/8f1cd356048289b42628835a1f25b144}
}
@ARTICLE{Wilkerson2011,
author = {Wilkerson, Paul M and Dedes, Konstantin J and Wetterskog, Daniel
and Mackay, Alan and Lambros, Maryou B and Mansour, Marthe and Frankum,
Jessica and Lord, Christopher J and Natrajan, Rachael and Ashworth,
Alan and Reis-Filho, Jorge S},
title = {Functional characterisation of EMSY gene amplification in human cancers},
journal = {The Journal of Pathology},
year = {2011},
pages = {n/a--n/a},
abstract = {Abstract The 11q13-q14 locus is frequently amplified in human cancers,
with a complex structure harbouring multiple potential oncogenic
drivers. The EMSY gene has been proposed as a driver of the third
core of the 11q13-q14 amplicon. This gene encodes a protein reported
to be a BRCA2 binding partner, which when overexpressed would lead
to impairment of BRCA2 functions and could constitute a mechanism
for BRCA2 inactivation in non-hereditary breast and ovarian cancers.
We hypothesised that if EMSY amplification abrogates BRCA2 functions,
cells harbouring this aberration would be unable to elicit competent
homologous recombination DNA repair, and, therefore, may have increased
sensitivity to genotoxic therapies and potent PARP inhibitors. Microarray-based
comparative genomic hybridisation of cell lines from distinct tumour
sites, including breast, ovary, pancreas, oesophageal, lung, and
the oral cavity, led to the identification of 10 cell lines with
EMSY amplification and 18 without. EMSY amplification was shown to
correlate with EMSY mRNA levels, although not all cell lines harbouring
EMSY amplification displayed EMSY mRNA or protein overexpression.
RNA interference mediated silencing of EMSY did not lead to a reduction
in cell viability in tumour models harbouring EMSY amplification.
Cell lines with and without EMSY amplification displayed a similar
ability to elicit RAD51 foci in response to DNA damaging agents,
and similar sensitivity to cisplatin and olaparib. Taken together,
this suggests that EMSY is unlikely to be a driver of the 11q13-q14
amplicon and does not have a dominant role in modulating the response
to agents targeting cells with defective homologous recombination.
Copyright © 2011 Pathological Society of Great Britain and Ireland.
Published by John Wiley & Sons, Ltd.},
doi = {10.1002/path.2944},
issn = {1096-9896},
keywords = {EMSY, 11q13 amplicon, cisplatin, PARP inhibitors, homologous recombination,
DNA repair, biomarker},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2944}
}
@ARTICLE{Wilkes2010,
author = {Wilkes, TM and Devonshire, AS and Ellison, SL and Foy, CA},
title = {Evaluation of a novel approach for the measurement of RNA quality.},
journal = {BMC Research Notes},
year = {2010},
volume = {3},
pages = {89},
number = {1},
month = apr,
abstract = {ABSTRACT: BACKGROUND: Microarray data interpretation can be affected
by sample RNA integrity. The ScreenTape Degradation Value (SDV) is
a novel RNA integrity metric specific to the ScreenTape(R) platform
(Lab901). To characterise the performance of the ScreenTape(R) platform
for RNA analysis and determine the robustness of the SDV metric,
a panel of intentionally degraded RNA samples was prepared. These
samples were used to evaluate the ScreenTape(R) platform against
an alternative approach for measuring RNA integrity (Agilent Bioanalyzer
RIN value). The samples were also subjected to microarray analysis
and the resulting data correlated to the RNA integrity metrics. FINDINGS:
Measurement of SDV for a panel of intentionally degraded RNA samples
ranged from 0 for intact RNA to 37 for degraded RNA, with corresponding
RIN values ranging from 10 to 4 for the same set of samples. SDV
and RIN scales both demonstrated comparable discrimination between
differently treated samples (RIN 10 to 7, SDV 0 to 15), with the
SDV exhibiting better discrimination at higher degradation levels.
Increasing SDV values correlated with a decrease in microarray sample
labelling efficiency and an increase in numbers of differentially
expressed genes. CONCLUSIONS: The ScreenTape(R) platform is comparable
to the Bioanalyzer platform in terms of reproducibility and discrimination
between different levels of RNA degradation. The robust nature of
the SDV metric qualifies it as an alternative metric for RNA sample
quality control, and a useful predictor of downstream microarray
performance.},
url = {http://www.biomedcentral.com/1756-0500/3/89}
}
@ARTICLE{Wilkins2012,
author = {E.J. Wilkins and J.P. Rubio and K.E. Kotschet and T.F. Cowie and
W.C. Boon and M. O’Hely and R. Burfoot and W. Wang and C.M. Sue
and T.P. Speed and J. Stankovitch and M.K. Horne},
title = {A DNA resequencing array for genes involved in Parkinson’s disease},
journal = {Parkinsonism \& Related Disorders},
year = {2012},
pages = { - },
number = {0},
abstract = {Parkinson’s disease (PD) is aetiologically complex with both familial
and sporadic forms. Familial PD results from rare, highly penetrant
pathogenic mutations whereas multiple variants of low penetrance
may contribute to the risk of sporadic PD. Common variants implicated
in PD risk appear to explain only a minor proportion of the familial
clustering observed in sporadic PD. It is therefore plausible that
combinations of rare and/or common variants in genes already implicated
in disease pathogenesis may help to explain the genetic basis of
PD.
We have developed a CustomSeq Affymetrix resequencing array to enable
high-throughput sequencing of 13 genes (44Â kb) implicated in the
pathogenesis of PD. Using the array we sequenced 269 individuals,
including 186 PD patients and 75 controls, achieving an overall call
rate of 96.5% and 93.6%, for two respective versions of the array,
and >99.9% accuracy for five samples sequenced by capillary sequencing
in parallel. We identified modest associations with common variants
in SNCA and LRRK2 and a trend suggestive of an overrepresentation
of rare variants in cases compared to controls for several genes.
We propose that this technology offers a robust and cost-effective
alternative to targeted sequencing using traditional sequencing methods,
and here we demonstrate the potential of this approach for either
routine clinical investigation or for research studies aimed at understanding
the genetic aetiology of PD.},
doi = {10.1016/j.parkreldis.2011.12.012},
issn = {1353-8020},
keywords = {Parkinsons disease},
url = {http://www.sciencedirect.com/science/article/pii/S1353802011004378}
}
@ARTICLE{Wilkinson2010,
author = {Wilkinson, Jamie and Sargent, Carole and Galina-Pantoja, Lucina and
Tucker, Alexander},
title = {Gene expression profiling in the lungs of pigs with different susceptibilities
to Glässer's disease},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {455},
number = {1},
abstract = {BACKGROUND:Haemophilus parasuis is the causative agent of Glässer's
disease in pigs. Currently, little is known about the molecular mechanisms
that contribute to disease susceptibility. This study used a porcine
oligonucleotide microarray to identify genes that were differentially
expressed (DE) in the lungs of colostrum-deprived animals previously
characterized as being either 'Fully Resistant' (FR) or 'Susceptible'
to infection by H. parasuis in a bacterial challenge experiment.RESULTS:Gene
expression profiles of 'FR' and 'Susceptible' animals were obtained
by the identification of genes that were differentially expressed
between each of these groups and mock-inoculated 'Control' animals.
At 24 hours post-inoculation, a total of 21 and 58 DE genes were
identified in 'FR' and 'Susceptible' animals respectively. At 72
hours, the numbers of genes were 20 and 347 respectively. 'FR' animals
at 24 hours exhibited an increased expression of genes encoding extracellular
matrix and TGF-ß signalling components, possibly indicative of tissue
repair following the successful early resolution of infection. The
gene expression profile of 'FR' animals at 72 hours supported the
hypothesis that higher levels of antibacterial activity were responsible
for the 'FR' phenotype, possibly due to an increase in natural immunoglobulin
A and decrease in signalling by the immunoregulatory transcription
factor peroxisome proliferator-activated receptor gamma (PPAR-?).
The expression profile of 'Susceptible' animals at both time-points
was characterized by an imbalance in signalling between pro and anti-inflammatory
cytokines and an increased expression of genes involved in biological
processes associated with inflammation. These include the pro-inflammatory
cytokine genes resistin (RETN) and interleukin 1-beta (IL1B). At
72 hours, a reduction in the expression of genes involved in antigen
presentation by both MHC class I and II molecules was observed, which
could have contributed to the inability of 'Susceptible' animals
to clear infection.CONCLUSIONS:This study is the first to have identified
discrete sets of DE genes in pigs of differing susceptibility to
H. parasuis infection. Consequently, several candidate genes and
pathways for disease resistance or susceptibility phenotypes have
been identified. In addition, the findings have shed light on the
molecular pathology associated with Glässer's disease.},
doi = {10.1186/1471-2164-11-455},
issn = {1471-2164},
pubmedid = {20670446},
url = {http://www.biomedcentral.com/1471-2164/11/455}
}
@ARTICLE{Wilkinson2007,
author = {Wilkinson, L.J. and Duffield, M.L. and Titball, R.W. and Lindsay,
C.D.},
title = {Down-regulation of gene transcripts associated with ricin tolerance
in human RPMI 2650 cells},
journal = {Toxicology in Vitro},
year = {2007},
volume = {21},
pages = {509--520},
number = {3},
month = apr,
abstract = {The present study sought to determine if novel therapeutic approaches
against ricin intoxication could be identified from human respiratory
tract cells selected for increased resistance to this toxin. Initial
studies indicated that the RPMI 2650 line was an appropriate model,
owing to its sensitivity to ricin. Tolerant cultures were developed
by exposing cells to a graded series of ricin concentrations from
6 to 192 pM. This resulted in the generation of cultures whose LC50
values were increased by up to 4-fold following exposure to up to
96 pM ricin and by up to 6-fold following exposure to up to 192 pM
ricin, compared to control cultures. DNA microarrays were employed
to determine the gene transcript expression profile of cultures with
increased resistance to ricin to investigate which gene products
mediate ricin resistance. Transcripts (10) were identified that were
greater than 2-fold down-regulated in the cells tolerant to 96 pM
ricin, whereas 48 transcripts were seen to be down-regulated in cultures
tolerant to 192 pM ricin. Gene transcripts (5) were up-regulated
2-fold or more in the 192 pM tolerant cultures in comparison to unexposed
cells. The results indicate that ricin tolerance is the product of
complex changes in gene expression profiles, most of which were found
to involve down-regulation of transcript expression. It may be possible
to modulate the gene expression profiles associated with ricin tolerance
for potential therapeutic purposes using drugs and antisense technologies.},
issn = {0887-2333},
keywords = {Human respiratory tract cells, Ricin, DNA microarrays, Toxin tolerance},
url = {http://www.sciencedirect.com/science/article/B6TCP-4M91NWY-2/2/6d62aae9baa2363e67d4a202461978b3}
}
@ARTICLE{Wilkinson2008,
author = {Wilkinson, Mark and Wan, Yongfang and Tosi, Paola and Leverington,
Michelle and Snape, John and Mitchell, Rowan A.C. and Shewry, Peter
R.},
title = {Identification and genetic mapping of variant forms of puroindoline
b expressed in developing wheat grain},
journal = {Journal of Cereal Science},
year = {2008},
volume = {48},
pages = {722--728},
number = {3},
month = nov,
abstract = {Transcripts encoding three novel variant forms of puroindoline b have
been identified in developing seeds of wheat. These show 57-60% sequence
identity with the wild type form of Pin b but all lack one of the
three tryptophan residues present in the "tryptophan loop" region
of the wild type protein. Counts of ESTs and array analysis indicate
that the transcripts encoding variant forms of Pin b are about an
order of magnitude less abundant than those encoding wild type Pin
b while array analysis also shows that expression of the variant
form 1 declines more rapidly than that of the wild type form during
the later stages of grain development. The gene(s) encoding variant
form 1, named Pinb-A2, were mapped to the long arm of chromosome
7A of bread wheat where they show linkage to novel QTLs for hardness
which have been identified in two doubled haploid populations derived
from crosses between hard parental cultivars (Shamrock × Shango,
Malacca × Charger).},
issn = {0733-5210},
keywords = {Wheat, Grain hardness, Puroindolines, Grain development, Genetic mapping},
url = {http://www.sciencedirect.com/science/article/B6WHK-4SD6SJC-1/2/4c9317d3f64513995983a6f9982106fb}
}
@ARTICLE{Wilks2009,
author = {Wilks, Jessica C. and Kitko, Ryan D. and Cleeton, Sarah H. and Lee,
Grace E. and Ugwu, Chinagozi S. and Jones, Brian D. and BonDurant,
Sandra S. and Slonczewski, Joan L.},
title = {Acid and Base Stress and Transcriptomic Responses in Bacillus subtilis},
journal = {Appl. Envir. Microbiol.},
year = {2009},
volume = {75},
pages = {981--990},
number = {4},
month = feb,
abstract = {Acid and base environmental stress responses were investigated in
Bacillus subtilis. B. subtilis AG174 cultures in buffered potassium-modified
Luria broth were switched from pH 8.5 to pH 6.0 and recovered growth
rapidly, whereas cultures switched from pH 6.0 to pH 8.5 showed a
long lag time. Log-phase cultures at pH 6.0 survived 60 to 100% at
pH 4.5, whereas cells grown at pH 7.0 survived <15%. Cells grown
at pH 9.0 survived 40 to 100% at pH 10, whereas cells grown at pH
7.0 survived <5%. Thus, growth in a moderate acid or base induced
adaptation to a more extreme acid or base, respectively. Expression
indices from Affymetrix chip hybridization were obtained for 4,095
protein-encoding open reading frames of B. subtilis grown at external
pH 6, pH 7, and pH 9. Growth at pH 6 upregulated acetoin production
(alsDS), dehydrogenases (adhA, ald, fdhD, and gabD), and decarboxylases
(psd and speA). Acid upregulated malate metabolism (maeN), metal
export (czcDO and cadA), oxidative stress (catalase katA; OYE family
namA), and the SigX extracytoplasmic stress regulon. Growth at pH
9 upregulated arginine catabolism (roc), which generates organic
acids, glutamate synthase (gltAB), polyamine acetylation and transport
(blt), the K+/H+ antiporter (yhaTU), and cytochrome oxidoreductases
(cyd, ctaACE, and qcrC). The SigH, SigL, and SigW regulons were upregulated
at high pH. Overall, greater genetic adaptation was seen at pH 9
than at pH 6, which may explain the lag time required for growth
shift to high pH. Low external pH favored dehydrogenases and decarboxylases
that may consume acids and generate basic amines, whereas high external
pH favored catabolism-generating acids.},
url = {http://aem.asm.org/cgi/content/abstract/75/4/981}
}
@ARTICLE{Willems2010,
author = {Willems, A. and De Gendt, K. and Allemeersch, J. and Smith, L. B.
and Welsh, M. and Swinnen, J. V. and Verhoeven, G.},
title = {Early effects of Sertoli cell-selective androgen receptor ablation
on testicular gene expression},
journal = {International Journal of Andrology},
year = {2010},
volume = {33},
pages = {507--517},
number = {3},
abstract = {Summary Evidence from several models of hormone depletion and/or replacement
and from knockout animals points to a key role of androgens in the
control of spermatogenesis. In testes of mice with a Sertoli cell-selective
ablation of the androgen receptor (SCARKO), transcriptional profiling,
using microarray technology, revealed that, already on postnatal
day 10Â 692 genes are differentially expressed compared with testes
of control mice. Further evaluation of a subset of these genes by
quantitative RT-PCR suggested that differences in expression may
already be evident on day 8 or earlier. As the androgen receptor
in mouse Sertoli cells becomes immunologically detectable around
day 5, we tried to identify the earliest responses to androgens by
a new transcriptional profiling study on testes from 6-day-old SCARKO
and control mice. No obvious and novel early androgen response genes,
potentially acting as mediators of subsequent indirect androgen actions,
could be identified. However, several genes differentially expressed
on day 10 already displayed a response to androgen receptor ablation
on day 6. Quantitative RT-PCR studies for 12 of these genes on 10
paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old
mice revealed significant differences in expression level from day
4 onwards for three genes (Eppin, PCI, Cldn11) and from day 6 onwards
for one more gene (Rhox5). For at least two of these genes (Rhox5
and Eppin), there is evidence for direct regulation via the androgen
receptor. For three additional genes (Gpd1, Tubb3 and Tpd52l1) significantly
lower expression in the SCARKO was noted from day 8 onwards. For
all the studied genes, an impressive increase in transcript levels
was observed between day 4–50 and differential expression was maintained
in adulthood. It is concluded that the SCARKO model indicates incipient
androgen action in mouse Sertoli cells from day 4 onwards.},
doi = {10.1111/j.1365-2605.2009.00964.x},
issn = {1365-2605},
keywords = {androgen action, microarray, quantitative RT-PCR, spermatogenesis,
transgenesis},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2605.2009.00964.x}
}
@ARTICLE{Willerslev2009,
author = {Willerslev, Eske and Gilbert, M Thomas and Binladen, Jonas and Ho,
Simon and Campos, Paula and Ratan, Aakrosh and Tomsho, Lynn and da
Fonseca, Rute and Sher, Andrei and Kuznetsova, Tatanya and Nowak-Kemp,
Malgosia and Roth, Terri and Miller, Webb and Schuster, Stephan},
title = {Analysis of complete mitochondrial genomes from extinct and extant
rhinoceroses reveals lack of phylogenetic resolution},
journal = {BMC Evolutionary Biology},
year = {2009},
volume = {9},
pages = {95},
number = {1},
abstract = {BACKGROUND:The scientific literature contains many examples where
DNA sequence analyses have been used to provide definitive answers
to phylogenetic problems that traditional (non-DNA based) approaches
alone have failed to resolve. One notable example concerns the rhinoceroses,
a group for which several contradictory phylogenies were proposed
on the basis of morphology, then apparently resolved using mitochondrial
DNA fragments.RESULTS:In this study we report the first complete
mitochondrial genome sequences of the extinct ice-age woolly rhinoceros
(Coelodonta antiquitatis), and the threatened Javan (Rhinoceros sondaicus),
Sumatran (Dicerorhinus sumatrensis), and black (Diceros bicornis)
rhinoceroses. In combination with the previously published mitochondrial
genomes of the white (Ceratotherium simum) and Indian (Rhinoceros
unicornis) rhinoceroses, this data set putatively enables reconstruction
of the rhinoceros phylogeny. While the six species cluster into three
strongly supported sister-pairings: (i) The black/white, (ii) the
woolly/Sumatran, and (iii) the Javan/Indian, resolution of the higher-level
relationships has no statistical support. The phylogenetic signal
from individual genes is highly diffuse, with mixed topological support
from different genes. Furthermore, the choice of outgroup (horse
vs tapir) has considerable effect on reconstruction of the phylogeny.
The lack of resolution is suggestive of a hard polytomy at the base
of crown-group Rhinocerotidae, and this is supported by an investigation
of the relative branch lengths.CONCLUSION:Satisfactory resolution
of the rhinoceros phylogeny may not be achievable without additional
analyses of substantial amounts of nuclear DNA. This study provides
a compelling demonstration that, in spite of substantial sequence
length, there are significant limitations with single-locus phylogenetics.
We expect further examples of this to appear as next-generation,
large-scale sequencing of complete mitochondrial genomes becomes
commonplace in evolutionary studies."The human factor in classification
is nowhere more evident than in dealing with this superfamily (Rhinocerotoidea)."
G. G. Simpson (1945)},
doi = {10.1186/1471-2148-9-95},
issn = {1471-2148},
pubmedid = {19432984},
url = {http://www.biomedcentral.com/1471-2148/9/95}
}
@ARTICLE{Willi-Monnerat2008,
author = {Willi-Monnerat, Susan and Migliavacca, Eugenia and Surdez, Didier
and Delorenzi, Mauro and Luthi-Carter, Ruth and Terskikh, Alexey
V.},
title = {Comprehensive spatiotemporal transcriptomic analyses of the ganglionic
eminences demonstrate the uniqueness of its caudal subdivision},
journal = {Molecular and Cellular Neuroscience},
year = {2008},
volume = {37},
pages = {845--856},
number = {4},
month = apr,
abstract = {The elucidation of mechanisms underlying telencephalic neural development
has been limited by the lack of knowledge regarding the molecular
and cellular aspects of the ganglionic eminence (GE), an embryonic
structure that supplies the brain with diverse sets of GABAergic
neurons. Here, we report a comprehensive transcriptomic analysis
of this structure including its medial (MGE), lateral (LGE) and caudal
(CGE) subdivisions and its temporal dynamics in 12.5 to 16 day-old
rat embryos. Surprisingly, comparison across subdivisions showed
that CGE gene expression was the most unique providing unbiased genetic
evidence for its differentiation from MGE and LGE. The molecular
signature of the CGE comprised a large set of genes, including Rwdd3,
Cyp26b1, Nr2f2, Egr3, Cpta1, Slit3, and Hod, of which several encode
cell signaling and migration molecules such as WNT5A, DOCK9, VSNL1
and PRG1. Temporal analysis of the MGE revealed differential expression
of unique sets of cell specification and migration genes, with early
expression of Hes1, Lhx2, Ctgf and Mdk, and late enrichment of Olfm3,
SerpinE2 and Wdr44. These GE profiles reveal new candidate regulators
of spatiotemporally governed GABAergic neuronogenesis.},
issn = {1044-7431},
keywords = {Ganglionic eminences, Gene expression profiling, Cerebral cortex,
Interneuronogenesis, Cortical interneurons, Rat},
url = {http://www.sciencedirect.com/science/article/B6WNB-4RP0MM6-2/2/1459c969c7ec79d3872ebbf481e333b5}
}
@ARTICLE{Williams2007,
author = {Williams, Alison S. and Issa, Razao and Leung, Sum Yee and Nath,
Puneeta and Ferguson, Gregory D. and Bennett, Brydon L. and Adcock,
Ian M. and Chung, Kian Fan},
title = {Attenuation of Ozone-Induced Airway Inflammation and Hyper-Responsiveness
by c-Jun NH2 Terminal Kinase Inhibitor SP600125},
journal = {J. Pharmacol. Exp. Ther.},
year = {2007},
volume = {322},
pages = {351--359},
number = {1},
month = jul,
abstract = {Ozone has potent oxidizing properties, and exposure to ozone causes
airway hyper-responsiveness (AHR) and lung inflammation. We determined
the importance of c-Jun NH2 terminal kinase (JNK), a member of the
mitogen-activated protein kinase pathway, in ozone-induced AHR and
inflammation. SP600125 [anthra[1,9-cd] pyrazol-6 (2H)-one], a specific
JNK inhibitor (30 mg/kg) or vehicle, was administered by intraperitoneal
injection before and after ozone exposure (3 ppm for 3 h). SP600125
significantly reduced total cells, and neutrophils in bronchoalveolar
fluid recovered at 20 to 24 h after exposure and inhibited ozone-induced
AHR. Ozone exposure induced activation of JNK in the lung as measured
by the expression of phosphorylated-c-Jun, an effect abolished by
SP600125. Gene-microarray analysis revealed that ozone increased
the expression of over 400 genes by more than 2-fold, including interleukin-6
(IL-6), CXCL1 (keratinocyte cytokine), and CCL2 (monocyte chemoattractant
protein-1). SP600125 modulated the expression of a subset of 29 ozone-induced
genes; IL-6 and CCL2 expression were further increased, whereas the
expression of metallothionein 1, hemopexin, and mitogen-activated
3 kinase 6 was decreased in SP600125-treated ozone-exposed mice.
Changes in mRNA for IL-6, CXCL1, and CCL2 were confirmed by real-time
polymerase chain reaction. Ozone also decreased the expression of
over 500 genes, with the most potent effect on angiopoietin-1. SP600125
modulated the expression of 15 of these genes, and in particular,
SP600125 reversed ozone-induced decrease in expression of the redox-sensitive
transcription factor, hypoxia-induced factor-1{alpha}. This study
highlights an important role for JNK in response to oxidative stress
through modulation of specific inflammatory and redox mediators.
Inhibition of JNK with small molecule kinase inhibitors may be a
means of reducing ozone-induced inflammation and AHR.},
url = {http://jpet.aspetjournals.org/cgi/content/abstract/322/1/351}
}
@ARTICLE{Williams2011,
author = {Williams, Cory T. and Goropashnaya, Anna V. and Buck, C. Loren and
Fedorov, Vadim B. and Kohl, Franziska and Lee, Trixie N. and Barnes,
Brian M.},
title = {Hibernating above the permafrost: effects of ambient temperature
and season on expression of metabolic genes in liver and brown adipose
tissue of arctic ground squirrels},
journal = {J. Exp. Biol.},
year = {2011},
volume = {214},
pages = {1300--1306},
number = {8},
month = apr,
abstract = {Hibernating arctic ground squirrels (Urocitellus parryii), overwintering
in frozen soils, maintain large gradients between ambient temperature
(Ta) and body temperature (Tb) by substantially increasing metabolic
rate during torpor while maintaining a subzero Tb. We used quantitative
reverse-transcription PCR (qRT-PCR) to determine how the expression
of 56 metabolic genes was affected by season (active in summer vs
hibernating), metabolic load during torpor (imposed by differences
in Ta: +2 vs -10{degrees}C) and hibernation state (torpid vs after
arousal). Compared with active ground squirrels sampled in summer,
liver from hibernators showed increased expression of genes associated
with fatty acid catabolism (CPT1A, FABP1 and ACAT1), ketogenesis
(HMGCS2) and gluconeogenesis (PCK1) and decreased expression of genes
associated with fatty acid synthesis (ACACB, SCD and ELOVL6), amino
acid metabolism, the urea cycle (PAH, BCKDHA and OTC), glycolysis
(PDK1 and PFKM) and lipid metabolism (ACAT2). Stage of hibernation
(torpid vs aroused) had a much smaller effect, with only one gene
associated with glycogen synthesis (GSY1) in liver showing consistent
differences in expression levels between temperature treatments.
Despite the more than eightfold increase in energetic demand associated
with defending Tb during torpor at a Ta of -10 vs +2{degrees}C, transcript
levels in liver and brown adipose tissue differed little. Our results
are inconsistent with a hypothesized switch to use of non-lipid fuels
when ambient temperatures drop below freezing.},
comment = {10.1242/jeb.052159},
url = {http://jeb.biologists.org/cgi/content/abstract/214/8/1300}
}
@ARTICLE{Williams2007a,
author = {Williams, Gary A. and Jacobs, Gerald H.},
title = {Cone-based vision in the aging mouse},
journal = {Vision Research},
year = {2007},
volume = {47},
pages = {2037--2046},
number = {15},
month = jul,
abstract = {People often experience age-related declines in cone-based visual
capacities despite an absence of apparent visual pathology. Although
mice are used as models of human visual pathologies associated with
aging, little is known about how age impacts vision in animals with
disease-free retinas since most studies have heretofore examined
relatively young mice. We examined the effects of age on cone-based
vision by assessing opsin gene transcription, cone densities, the
flicker electroretinogram (ERG), and behavioral increment thresholds
in mice. ERG measurements of cone function showed age-related declines
in maximum voltage (Vmax), while opsin gene transcription, cone density,
and increment thresholds were unchanged even in extremely old mice.
The age-related decline in Vmax seen in mice is qualitatively similar
to that documented for human subjects. It is notable that Vmax, a
commonly used index of ERG activity, does not predict behavioral
performance in the mouse.},
issn = {0042-6989},
keywords = {Aging, Photoreceptor, Opsin, Electroretinogram (ERG), Behavioral sensitivity,
Mus musculus},
url = {http://www.sciencedirect.com/science/article/B6T0W-4NRMD3Y-1/2/274202e0af2cb4f1557e1e35cd85bcf5}
}
@ARTICLE{Williams2010a,
author = {Williams, J. A. and Faber, C. and Holst Nissen, M. and Greenwood,
J. and Moss, S. E.},
title = {Microarray Analysis of Aged RPE and Choroid in CFH -/- Mice},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {6132--},
number = {5},
month = apr,
abstract = {PurposeThe Y402H single nucleotide polymorphism in the complement
regulator, Complement Factor H (CFH), is associated with increased
susceptibility to Age-related Macular Degeneration (AMD). The contribution
of this variant of CFH to the pathology of AMD is not well characterised.
To understand how Y402H contributes to AMD pathology we performed
microarray analysis of the RPE/choroid in wild type (WT) and cfh-/-
mice to investigate the transcriptional changes in response to the
loss of this complement regulator in both young and aged mice. MethodsRPE/choroid
RNA was isolated from young (7-8 weeks) and old (16 months) WT and
cfh-/- C57Bl/6 mice. RNA was extracted using Trizol followed by RNeasy
clean up (QIAgen). DNA was removed by DNase I digestion and RNA quality
was assessed using the Agilent Bioanalyser. RNA was linearly amplified
(NuGEN), labelled and hybridized to Mouse Gene 1.0 ST Affymetrix
chips. Four chips were used per group of which each contained cDNA
from one mouse. Data underwent background adjustment, normalisation
and summarisation. Differential expression was analysed using ANOVA
and Benjamini-Hochberg (FDR) test was applied for multiple correction.
ResultsIn young mice loss of CFH significantly changed the transcription
of 4 genes (p value < 0.05). With age this increased to 33 genes
of which only 17 encoded known proteins. Three of the four genes
that were altered in young mice were also significantly different
in aged mice. Ageing in WT animals resulted in significant differential
regulation of 657 genes compared with 543 in cfh-/- mice, with 243
of these genes being common to both WT and cfh-/-. ConclusionsPrevious
work from our lab has shown that the loss of CFH in aged mice causes
retinal abnormalities and visual dysfunction. Here we report that
loss of the complement regulator, CFH, causes transcriptional changes
in the RPE/choroid even in young mice. The loss of CFH has a greater
effect with age. Fewer than 50% of the genes changing with age were
the same for both WT and cfh-/-, suggesting that the transcriptomics
of ageing are significantly different in the absence of CFH. We anticipate
that some of the genes identified will have causative roles in the
functional and anatomical changes observed in the aged cfh-/- retina.},
url = {http://abstracts.iovs.org/cgi/content/abstract/51/5/6132}
}
@ARTICLE{Williams2009,
author = {Williams, J. Bradley and Pang, Diana and Delgado, Bertha and Kocherginsky,
Masha and Tretiakova, Maria and Krausz, Thomas and Pan, Deng and
He, Jane and McClintock, Martha K. and Conzen, Suzanne D.},
title = {A Model of Gene-Environment Interaction Reveals Altered Mammary Gland
Gene Expression and Increased Tumor Growth following Social Isolation},
journal = {Cancer Prevention Research},
year = {2009},
volume = {2},
pages = {850--861},
number = {10},
month = oct,
abstract = {Clinical studies have revealed that social support improves the outcome
of cancer patients, whereas epidemiologic studies suggest that social
isolation increases the risk of death associated with several chronic
diseases. However, the precise molecular consequences of an unfavorable
social environment have not been defined. To do so, robust, reproducible
preclinical models are needed to study the mechanisms whereby an
adverse environment affects gene expression and cancer biology. Because
random assignment of inbred laboratory mice to well-defined social
environments allows accurate and repeated measurements of behavioral
and endocrine parameters, transgenic mice provide a preclinical framework
with which to begin to determine gene-environment mechanisms. In
this study, we found that female C3(1)/SV40 T-antigen mice deprived
of social interaction from weaning exhibited increased expression
of genes encoding key metabolic pathway enzymes in the premalignant
mammary gland. Chronic social isolation was associated with up-regulated
lipid synthesis and glycolytic pathway gene expression--both pathways
are known to contribute to increased breast cancer growth. Consistent
with the expression of metabolic genes in premalignant mammary tissue,
isolated mice subsequently developed a significantly larger mammary
gland tumors burden compared with group-housed mice. Endocrine evaluation
confirmed that isolated mice developed a heightened corticosterone
stress response compared with group-housed mice. Together, these
transdisciplinary studies show for the first time that an adverse
social environment is associated with altered mammary gland gene
expression and tumor growth. Moreover, the identification of specific
alterations in metabolic pathways gene expression favoring tumor
growth suggests potential molecular biomarkers and/or targets (e.g.,
fatty acid synthesis) for preventive intervention in breast cancer.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/2/10/850}
}
@ARTICLE{Williams2008,
author = {Williams, Jeffrey G. and Ojaimi, Caroline and Qanud, Khaled and Zhang,
Suhua and Xu, Xiaobin and Recchia, Fabio A. and Hintze, Thomas H.},
title = {Coronary nitric oxide production controls cardiac substrate metabolism
during pregnancy in the dog},
journal = {Am J Physiol Heart Circ Physiol},
year = {2008},
volume = {294},
pages = {H2516--2523},
number = {6},
month = jun,
abstract = {The aim of this study was to examine the role of nitric oxide (NO)
in the control of cardiac metabolism at 60 days of pregnancy (P60)
in the dog. There was a basal increase in diastolic coronary blood
flow during pregnancy and a statistically significant increase in
cardiac output (55 {+/-} 4%) and in cardiac NOx production (44 {+/-}
4 to 59 {+/-} 3 nmol/min, P < 0.05). Immunohistochemistry of the
left ventricle showed an increase in endothelial nitric oxide synthase
staining in the endothelial cells at P60. NO-dependent coronary vasodilation
(Bezold-Jarisch reflex) was increased by 20% and blocked by NG-nitro-L-arginine
methyl ester (L-NAME). Isotopically labeled substrates were infused
to measure oleate, glucose uptake, and oxidation. Glucose oxidation
was not significantly different in P60 hearts (5.4 {+/-} 0.5 vs.
6.2 {+/-} 0.4 {micro}mol/min) but greatly increased in response to
L-NAME injection (to 19.9 {+/-} 0.9 {micro}mol/min, P < 0.05). Free
fatty acid (FFA) oxidation was increased in P60 (from 5.3 {+/-} 0.6
to 10.4 {+/-} 0.5 {micro}mol/min, P < 0.05) and decreased in response
to L-NAME (to 4.5 {+/-} 0.5 {micro}mol/min, P < 0.05). There was
an increased oxidation of FFA for ATP production but no change in
the respiratory quotient during pregnancy. Genes associated with
glucose and glycogen metabolism were downregulated, whereas genes
involved in FFA oxidation were elevated. The acute inhibition of
NO shifts the heart away from FFA and toward glucose metabolism despite
the downregulation of the carbohydrate oxidative pathway. The increase
in endothelium-derived NO during pregnancy results in a tonic inhibition
of glucose oxidation and reliance on FFA uptake and oxidation to
support ATP synthesis in conjunction with upregulation of FFA metabolic
enzymes.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/294/6/H2516}
}
@ARTICLE{Williams2009a,
author = {Williams, Marcie R. and Sakurai, Yumiko and Zughaier, Susu M. and
Eskin, Suzanne G. and McIntire, Larry V.},
title = {Transmigration across activated endothelium induces transcriptional
changes, inhibits apoptosis, and decreases antimicrobial protein
expression in human monocytes},
journal = {J. Leukoc. Biol.},
year = {2009},
volume = {86},
pages = {1331--1343},
number = {6},
month = dec,
abstract = {We investigated the hypothesis that transmigration drives monocyte
transcriptional changes. Using Agilent whole human genome microarrays,
we identified over 692 differentially expressed genes (2x, P<0.05)
in freshly isolated human monocytes following 1.5 h of transmigration
across IL-1{beta}-stimulated ECs compared with untreated monocytes.
Genes up-regulated by monocyte transmigration belong to a number
of over-represented functional groups including immune response and
inhibition of apoptosis. qRT-PCR confirmed increased expression of
MCP-1 and -3 and of NAIP following monocyte transmigration. Additionally,
quantification of Annexin V binding revealed a reduction in apoptosis
following monocyte transmigration. Comparison of gene expression
in transmigrated monocytes with additional controls (monocytes that
failed to transmigrate and monocytes incubated beneath stimulated
ECs) revealed 89 differentially expressed genes, which were controlled
by the process of diapedesis. Functional annotation of these genes
showed down-regulation of antimicrobial genes (e.g., {alpha}-defensin
down 50x, cathelicidin down 9x, and CTSG down 3x). qRT-PCR confirmed
down-regulation of these genes. Immunoblots confirmed that monocyte
diapedesis down-regulates {alpha}-defensin protein expression. However,
transmigrated monocytes were functional and retained intact cytokine
and chemokine release upon TLR ligand exposure. Overall, these data
indicate that the process of monocyte transmigration across stimulated
ECs promotes further monocyte recruitment and inhibits monocyte apoptosis.
Unexpectedly, following transmigration, monocytes displayed reduced
antimicrobial protein expression.},
url = {http://www.jleukbio.org/cgi/content/abstract/86/6/1331}
}
@ARTICLE{Williams2010b,
author = {Williams, P. Mickey and Li, Rui and Johnson, Nathalie A. and Wright,
George and Heath, Joe-Don and Gascoyne, Randy D.},
title = {A Novel Method of Amplification of FFPET-Derived RNA Enables Accurate
Disease Classification with Microarrays},
journal = {J. Mol. Diagn.},
year = {2010},
volume = {12},
pages = {680--686},
number = {5},
month = sep,
abstract = {A new method for amplification and labeling of RNA is assessed that
permits gene expression microarray analysis of formalin-fixed paraffin-embedded
tissue (FFPET) samples. Valid biological data were obtained using
gene expression microarrays of diffuse large B-cell lymphoma (DLBCL)
FFPET samples. We examined 59 matched DLBCL patient samples, FFPET,
and fresh/frozen. The samples contained both prognostic subgroups
of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC).
Fresh/frozen (FF) samples were amplified by both the traditional
Eberwine oligo-dT method and a new method described herein. The matching
FFPET samples were also amplified using the new method. Here we detail
the comparison of results from all three datasets of matched samples.
An established classification model built from previous data accurately
classified these new samples. This new method provides a useful technology
advance for microarray analysis of FFPET archival samples.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/12/5/680}
}
@ARTICLE{Williams2010,
author = {Williams, Tracy A. and Monticone, Silvia and Morello, Fulvio and
Liew, Choong-Chin and Mengozzi, Giulio and Pilon, Catia and Asioli,
Sofia and Sapino, Anna and Veglio, Franco and Mulatero, Paolo},
title = {Teratocarcinoma-Derived Growth Factor-1 Is Upregulated in Aldosterone-Producing
Adenomas and Increases Aldosterone Secretion and Inhibits Apoptosis
In Vitro},
journal = {Hypertension},
year = {2010},
volume = {55},
pages = {1468--1475},
number = {6},
month = jun,
abstract = {Aldosterone-producing adenomas (APA) are a frequent cause of secondary
hypertension characterized by autonomous hypersecretion of aldosterone.
However, the molecular mechanisms involved in adrenal tumorigenesis
and deregulated aldosterone secretion are currently unknown. To identify
putative functional genes, a transcriptional screening was performed
on 8 APA and 3 normal adrenals (NA) using oligonucleotide microarrays.
Data were next validated on an expanded set of samples by real-time
PCR (APA, n=19; NA, n=10). The epidermal growth factor-like teratocarcinoma-derived
growth factor-1 (TDGF-1) was upregulated in APA compared with NA
(14.7-fold and 21.4-fold by microarray and real-time PCR, respectively).
In vitro studies and Western blot analysis using the NCI H295R adrenocortical
cell line showed that TDGF-1 increased Akt phosphorylation on Thr308
and Ser473, consistent with activation of phosphatidylinositol 3-kinase/Akt
signaling, and also demonstrated a concomitant inactivation of the
Akt substrate glycogen synthesis kinase-3{beta} via Ser9 phosphorylation.
Furthermore, TDGF-1 mediated a 3.8{+/-}0.4-fold increase in aldosterone
secretion (n=4) that was specifically blocked by the phosphatidylinositol
3-kinase inhibitors wortmannin (50 nmol/L) and LY294002 (20 {micro}mol/L).
Finally, TDGF-1 protected H295R cells from apoptosis induced by staurosporine,
causing a decrease in caspase-3 activity, a reduction in the inactivation
of poly(ADP-ribose) polymerase, and an inhibition of DNA fragmentation,
detected by the TUNEL reaction and fluorescence microscopy that was
blocked by LY294002. Taken together, our data suggest that TDGF-1,
which is significantly upregulated in APA and mediates aldosterone
hypersecretion and deregulated growth in adrenocortical cells in
vitro, may represent a key player in the development and pathophysiology
of primary aldosteronism.},
url = {http://hyper.ahajournals.org/cgi/content/abstract/55/6/1468}
}
@ARTICLE{Williams2003,
author = {Williams, T. D. and Gensberg, K. and Minchin, S. D. and Chipman,
J. K.},
title = {A DNA expression array to detect toxic stress response in European
flounder (Platichthys flesus)},
journal = {Aquatic Toxicology},
year = {2003},
volume = {65},
pages = {141--157},
number = {2},
month = oct,
abstract = {As a first stage in developing a DNA array-based approach to investigating
the effects of pollutants on an environmentally relevant European
fish species, we have constructed a 160-gene custom microarray for
European flounder. Degenerate primers were used to amplify 110 different
fragments of stress-related and other genes from European flounder
cDNA and genomic DNA. Additionally, 22 fragments were obtained by
suppressive subtractive hybridisation (SSH). These fragments were
cloned and sequenced, then, with additional control genes, used to
create a cDNA microarray for flounder. After optimisation of the
arraying process, hepatic mRNA was isolated from flounder caught
in the polluted Tyne and relatively unpolluted Alde estuaries. Fluorescent
cDNA probes were synthesised from the mRNA and used in dual-colour
hybridisations to the microarray. A number of transcripts were differentially
expressed between Tyne and Alde female flounder but these changes
were not significant, due to high inter-individual variation. However,
in comparisons between Tyne and Alde male flounder, 11 transcripts
were found to significantly differ in expression (P<0.05). Seven
transcripts were more highly expressed in the Tyne male fish (CYP1A,
UDPGT, [alpha]-2HS-glycoprotein, dihydropyrimidine dehydrogenase,
Cu/Zn SOD, aldehyde dehydrogenase and paraoxonase). Four transcripts
(Elongation factor 1 (EF1), EF2, Int-6 and complement component C3)
were found to be significantly less abundant in the Tyne male fish.
Selected genes were assayed by real-time PCR, then normalised to
[alpha]-tubulin. These assays confirmed the significance of the array
results for CYP1A, UDPGT and EF1, but not for Cu/Zn SOD. This study
provides a link between traditional single-gene biomarker studies
and the emerging field of eco-toxicogenomics, demonstrating the utility
of microarray studies on environmentally sampled, non-model organisms.},
issn = {0166-445X},
keywords = {Microarray, cDNA array, Flounder, Real-time PCR, CYP1A, Toxicogenomics},
url = {http://www.sciencedirect.com/science/article/B6T4G-493PBJ8-3/2/481da79a36e27d7ad35a004977dae145}
}
@ARTICLE{Williamson2010,
author = {Williamson, David L. and Raue, Ulrika and Slivka, Dustin R. and Trappe,
Scott},
title = {Resistance Exercise, Skeletal Muscle FOXO3A, and 85-Year-Old Women},
journal = {J Gerontol A Biol Sci Med Sci},
year = {2010},
volume = {65A},
pages = {335--343},
number = {4},
month = apr,
abstract = {This investigation examined Akt-FOXO3A signaling in young women (YW)
and old women (OW) before and after 12 weeks of high-intensity resistance
training. Muscle biopsies were taken from the vastus lateralis before
and immediately after resistance exercise (RE) in the untrained and
trained states. In response to RE in YW and OW, phospho Akt Thr308
increased in untrained and trained states, with no change on Ser473
site. FOXO3A-Ser253 site was dephosphorylated in untrained state
among YW and OW, and nuclear phospho-FOXO3A increased mainly in YW
in trained state. In the basal state, OW displayed lower cytosolic
phospho-FOXO3A before training, higher total nuclear FOXO3A, and
a trend for higher nuclear-to-cytosolic FOXO3A ratio versus YW after
12 weeks. Basal level MuRF-1 and myostatin mRNA decreased in YW,
while OW increased myostatin mRNA after 12-weeks. These data suggest
that FOXO3A signaling and FOXO3A-related target gene expression are
altered in OW and may partially explain the attenuated training adaptations
previously reported in these octogenarian women.},
url = {http://biomedgerontology.oxfordjournals.org/cgi/content/abstract/65A/4/335}
}
@ARTICLE{Willing2010,
author = {Willing, Ben P. and Dicksved, Johan and Halfvarson, Jonas and Andersson,
Anders F. and Lucio, Marianna and Zheng, Zongli and Järnerot, Gunnar
and Tysk, Curt and Jansson, Janet K. and Engstrand, Lars},
title = {A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial
Profiles Vary With Inflammatory Bowel Disease Phenotypes},
journal = {Gastroenterology},
year = {2010},
volume = {139},
pages = {1844--1854.e1},
number = {6},
month = dec,
abstract = {Background & Aims The composition of the gastrointestinal microbiota
is thought to have an important role in the etiology of inflammatory
bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative
colitis (UC). Interindividual variation and an inability to detect
less abundant bacteria have made it difficult to correlate specific
bacteria with disease.Methods We used 454 pyrotag sequencing to determine
the compositions of microbial communities in feces samples collected
from a cohort of 40 twin pairs who were concordant or discordant
for CD or UC, and in mucosal samples from a subset of the cohort.
The cohort primarily comprised patients who were in remission, but
also some with active disease.Results The profiles of the microbial
community differed with disease phenotypes; relative amounts of bacterial
populations correlated with IBD phenotypes. The microbial compositions
of individuals with CD differed from those of healthy individuals,
but were similar between healthy individuals and individuals with
UC. Profiles from individuals with CD that predominantly involved
the ileum differed from those with CD that predominantly involved
the colon; several bacterial populations increased or decreased with
disease type. Changes specific to patients with ileal CD included
the disappearance of core bacteria, such as Faecalibacterium and
Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus
gnavus.Conclusions Bacterial populations differ in abundance among
individuals with different phenotypes of CD. Specific species of
bacteria are associated with ileal CD; further studies should investigate
their role in pathogenesis.},
issn = {0016-5085},
keywords = {Gastrointestinal Microbiome, CCD, ICD, Pyrosequencing, Microbial Profiling},
url = {http://www.sciencedirect.com/science/article/pii/S0016508510012990}
}
@ARTICLE{Willinger2005,
author = {Willinger, Tim and Freeman, Tom and Hasegawa, Hitoshi and McMichael,
Andrew J. and Callan, Margaret F. C.},
title = {Molecular Signatures Distinguish Human Central Memory from Effector
Memory CD8 T Cell Subsets},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {5895--5903},
number = {9},
month = nov,
abstract = {Memory T cells are heterogeneous in terms of their phenotype and functional
properties. We investigated the molecular profiles of human CD8 naive
central memory (TCM), effector memory (TEM), and effector memory
RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific
intracellular flow cytometry. We demonstrate that TCM have a gene
expression and cytokine signaling signature that lies between that
of naive and TEM or TEMRA cells, whereas TEM and TEMRA are closely
related. Our data define the molecular basis for the different functional
properties of central and effector memory subsets. We show that TEM
and TEMRA cells strongly express genes with known importance in CD8
T cell effector function. In contrast, TCM are characterized by high
basal and cytokine-induced STAT5 phosphorylation, reflecting their
capacity for self-renewal. Altogether, our results distinguish TCM
and TEM/TEMRA at the molecular level and are consistent with the
concept that TCM represent memory stem cells.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/9/5895}
}
@ARTICLE{Willis2008,
author = {Willis, Amanda L. and Tran, Nhan L. and Chatigny, Julie M. and Charlton,
Nichole and Vu, Hong and Brown, Sharron A.N. and Black, Michael A.
and McDonough, Wendy S. and Fortin, Shannon P. and Niska, Joshua
R. and Winkles, Jeffrey A. and Cunliffe, Heather E.},
title = {The Fibroblast Growth Factor-Inducible 14 Receptor Is Highly Expressed
in HER2-Positive Breast Tumors and Regulates Breast Cancer Cell Invasive
Capacity},
journal = {Mol. Cancer Res.},
year = {2008},
volume = {6},
pages = {725--734},
number = {5},
month = may,
abstract = {Genomic characterization is beginning to define a molecular taxonomy
for breast cancer; however, the molecular basis of invasion and metastasis
remains poorly understood. We report a pivotal role for the fibroblast
growth factor-inducible 14 (Fn14) receptor in this process. We examined
whether Fn14 and its ligand tumor necrosis factor-like weak inducer
of apoptosis (TWEAK) were expressed in breast tumors and whether
deregulation of Fn14 levels affected malignant behavior of breast
cancer cell lines. Analysis of TWEAK and Fn14 in publicly available
gene expression data indicated that high Fn14 expression levels significantly
correlated with several poor prognostic indicators (P < 0.05). Fn14
expression was highest in the HER2-positive/estrogen receptor-negative
(HER2+/ER-) intrinsic subtype (P = 0.0008). An association between
Fn14 and HER2 expression in breast tumors was confirmed by immunohistochemistry.
Fn14 levels were elevated in invasive, ER- breast cancer cell lines.
Overexpression of Fn14 in weakly invasive MCF7 and T47D cells resulted
in a marked induction of invasion and activation of nuclear factor-{kappa}B
(NF-{kappa}B) signaling. Ectopic expression of Fn14tCT, a Fn14 deletion
mutant that cannot activate NF-{kappa}B signaling, was not able to
induce invasion. Moreover, ectopic expression of Fn14tCT in highly
invasive MDA-MB-231 cells reduced their invasive capability. RNA
interference-mediated inhibition of Fn14 expression in both MDA-MB-231
and MDA-MB-436 cells reduced invasion. Expression profiling of the
Fn14-depleted cells revealed deregulation of NF-{kappa}B activity.
Our findings support a role for Fn14-mediated NF-{kappa}B pathway
activation in breast tumor invasion and metastasis. (Mol Cancer Res
2008;6(5):725-34)},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/6/5/725}
}
@ARTICLE{Willmann2011,
author = {Willmann, Gabriel and Schaferhoff, Karin and Fischer, Manuel D. and
Arango-Gonzalez, Blanca and Bolz, Sylvia and Naycheva, Lubka and
Rock, Tobias and Bonin, Michael and Bartz-Schmidt, Karl U. and Zrenner,
Eberhart and Schatz, Andreas and Gekeler, Florian},
title = {Gene Expression Profiling of the Retina after Transcorneal Electrical
Stimulation in Wild-type Brown Norway Rats},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2011},
volume = {52},
pages = {7529-7537},
number = {10},
abstract = {Purpose.Transcorneal electrical stimulation (TES) has been beneficial
in several neurodegenerative ocular diseases, but the exact mechanisms
remain to be elucidated. This study was conducted to investigate
the effects of TES on the retinas of wild-type Brown Norway (BN)
rats by gene expression profiling and to assess its effects on retinal
function and morphology. Methods.TES was applied to BN wild-type
rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz; 200
{micro}A). RNA was isolated and processed for microarray-based profiling
4 hours after TES; differentially expressed genes from TES compared
with those from sham-treated animals were validated by quantitative
real-time polymerase chain reaction. Furthermore, the effect of TES
was assessed at the structural and functional levels using electroretinography,
confocal scanning laser ophthalmoscopy, optical coherence tomography,
and immunohistochemistry. Results.Transcriptome changes associated
with TES versus sham-stimulated BN wild-type retina were identified.
Four hundred ninety genes were differentially expressed in TES and
included potentially neuroprotective genes such as Bax or members
of the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b,
Tnfsf13). ERG recordings showed physiological retinal function after
TES, and structural in vivo and ex vivo studies revealed intact retinal
anatomy. Conclusions.These results demonstrate that TES applied to
the retina of the wild-type BN rats induces distinct transcriptome
level changes and may help in the understanding of the mechanisms
underlying TES. In addition, TES treatment indicates no negative
effect on structure and function of the wild-type BN retina up to
35 hours after application.},
doi = {10.1167/iovs.11-7838},
eprint = {http://www.iovs.org/cgi/reprint/52/10/7529.pdf},
url = {http://www.iovs.org/cgi/content/abstract/52/10/7529}
}
@ARTICLE{Willoughby2008,
author = {Willoughby, Kim and Thomson, Karen and Maley, Madeleine and Gilray,
Janice and Scholes, Sandra and Howie, Fiona and Caldow, George and
Nettleton, Peter F.},
title = {Development of a real time reverse transcriptase polymerase chain
reaction for the detection of bovine respiratory syncytial virus
in clinical samples and its comparison with immunohistochemistry
and immunofluorescence antibody testing},
journal = {Veterinary Microbiology},
year = {2008},
volume = {126},
pages = {264--270},
number = {1-3},
month = jan,
issn = {0378-1135},
keywords = {Bovine respiratory syncytial virus (BRSV), Diagnosis, Real time RT-PCR,
Immunohistochemistry, Immunofluorescence},
url = {http://www.sciencedirect.com/science/article/B6TD6-4P59X7D-1/2/933ac88c3826382bfbf1afce0be083a6}
}
@ARTICLE{Willoughby2006,
author = {Willoughby, K. and Valdazo-González, B. and Maley, M. and Gilray,
J. and Nettleton, P.F.},
title = {Development of a real time RT-PCR to detect and type ovine pestiviruses},
journal = {Journal of Virological Methods},
year = {2006},
volume = {132},
pages = {187--194},
number = {1-2},
month = mar,
abstract = {A real time one-step RT-PCR was designed to detect and type border
disease virus (BDV), bovine viral diarrhea virus (BVDV) type 1 and
BVDV type 2 in ovine samples. The real time RT-PCR was shown to behave
in a linear manner and had limits of detection of 100-1000 copies
of viral RNA as judged by in vitro transcribed RNA. The real time
RT-PCR was validated on 50 clinical samples from UK flocks and was
more sensitive than a virus isolation and a classical nested RT-PCR
(nRT-PCR). The results of real time RT-PCR virus typing agreed completely
with sequencing. The majority of ovine isolates were BDV; a small
proportion were BVDV type 1. BVDV type 2 was not detected in any
sample. This test appears reliable and can be used for the typing
of ovine pestiviruses in the UK.},
issn = {0166-0934},
keywords = {Pestivirus, BDV, BVDV, Real time RT-PCR, PCR, TaqMan},
url = {http://www.sciencedirect.com/science/article/B6T96-4HMNFSN-1/2/34ad2f28dea6e2a039dd1d5556733015}
}
@ARTICLE{Wilmes2011,
author = {Wilmes, Anja and Crean, Daniel and Aydin, Sonia and Pfaller, Walter
and Jennings, Paul and Leonard, Martin O.},
title = {Identification and dissection of the Nrf2 mediated oxidative stress
pathway in human renal proximal tubule toxicity},
journal = {Toxicology in Vitro},
year = {2011},
volume = {25},
pages = {613--622},
number = {3},
month = apr,
abstract = {The identification and dissection of cellular stress mechanisms is
fundamental to understanding the susceptibility of the kidney to
chemicals and pharmaceuticals and for the development of renal biomarkers
indicative of sub lethal injury. Here, we utilised whole genome DNA
microarrays in an attempt to uncover molecular mechanisms of response
to nephrotoxin exposure. Human renal proximal tubular cells (HK-2)
were treated for 12 h and 48 h with 5 [mu]M Cadmium (Cd), 30 [mu]M
Diquat Dibromide (Diq), and 5 [mu]M Cyclosporine A (CsA). Nephrotoxin
treatment resulted in an alteration of a total of 4608 transcripts.
Ingenuity Pathways Analysis(TM) revealed the anti-oxidant and detoxification
Nrf2 pathway as the most significantly enriched signaling pathway
in the selected dataset. Activation of this transcription factor
was confirmed as nuclear translocation and paralleled the temporal
alterations of compound induced H2O2 production. Transcriptomics,
western blot and immunofluorescence showed an induction of both HO-1
and NQO1 with Cd and Diq exposure, but not with CsA treatment. Knockdown
of Nrf2 by siRNA, reduced compound induced NQO1 mRNA to basal levels
and attenuated toxin induced HO-1 mRNA expression. siRNA knock down
of HO-1, but not NQO1, enhanced Cd induced H2O2 production and Cd
induced toxicity. Using an un-biased transcriptomic approach we have
identified the Nrf2 pathway as the most significant signaling response
in renal epithelial cells challenged with nephrotoxin. This study
highlights the importance of this pathway and particularly HO-1 in
renal epithelial adaptation to oxidative stress.},
issn = {0887-2333},
keywords = {Nrf2, NQO1, HO-1, Proximal tubule, Nephrotoxicity, Cadmium, Cyclosporine
A, Diquat dibromide, DNA microarray},
url = {http://www.sciencedirect.com/science/article/pii/S088723331000336X}
}
@ARTICLE{Wilmink2011,
author = {Wilmink, Gerald J. and Rivest, Benjamin D. and Roth, Caleb C. and
Ibey, Bennett L. and Payne, Jason A. and Cundin, Luisiana X. and
Grundt, Jessica E. and Peralta, Xomalin and Mixon, Dustin G. and
Roach, William P.},
title = {In vitro investigation of the biological effects associated with
human dermal fibroblasts exposed to 2.52 THz radiation},
journal = {Lasers in Surgery and Medicine},
year = {2011},
volume = {43},
pages = {152--163},
number = {2},
abstract = {Abstract BackgroundTerahertz (THz) radiation sources are increasingly
being used in military, defense, and medical applications. However,
the biological effects associated with this type of radiation are
not well characterized. In this study, we evaluated the cellular
and molecular response of human dermal fibroblasts exposed to THz
radiation.MethodsIn vitro exposures were performed in a temperature-controlled
chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm−2,
durations: 5, 10, 20, 40, or 80 minutes). Both computational and
empirical dosimetric techniques were conducted using finite-difference
time-domain (FDTD) modeling approaches, infrared cameras, and thermocouples.
Cellular viability was assessed using conventional MTT assays. In
addition, the transcriptional activation of protein and DNA sensing
genes were evaluated using qPCR. Comparable analyses were also conducted
for hyperthermic and genotoxic positive controls.ResultsWe found
that cellular temperatures increased by 3°C during all THz exposures.
We also found that for each exposure duration tested, the THz and
hyperthermic exposure groups exhibited equivalent levels of cell
survival (≥90%) and heat shock protein expression (∼3.5-fold
increases). In addition, the expression of DNA sensing and repair
genes was unchanged in both groups; however, appreciable increases
were observed in the genotoxic controls.ConclusionsHuman dermal fibroblasts
exhibit comparable cellular and molecular effects when exposed to
THz radiation and hyperthermic stress. These findings suggest that
radiation at 2.52 THz generates primarily thermal effects in mammalian
cells. Therefore, we conclude that THz-induced bioeffects may be
accurately predicted with conventional thermal damage models. Lasers
Surg. Med. 42:152–163, 2011 © 2010 Wiley-Liss, Inc.},
doi = {10.1002/lsm.20960},
issn = {1096-9101},
keywords = {terahertz, bioeffects, radiation, THz, applications},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/lsm.20960}
}
@ARTICLE{Wilmot2008,
author = {Wilmot, Beth and McWeeney, Shannon K. and Nixon, Randal R. and Montine,
Thomas J. and Laut, Jamie and Harrington, Christina A. and Kaye,
Jeffrey A. and Kramer, Patricia L.},
title = {Translational gene mapping of cognitive decline},
journal = {Neurobiology of Aging},
year = {2008},
volume = {29},
pages = {524--541},
number = {4},
month = apr,
abstract = {The ability to maintain cognitive function during aging is a complex
process subject to genetic and environmental influences. Alzheimer's
disease (AD) is the most common disorder causing cognitive decline
among the elderly. Among those with AD, there is broad variation
in the relationship between AD neuropathology and clinical manifestations
of dementia. Differences in expression of genes involved in neural
processing pathways may contribute to individual differences in maintenance
of cognitive function. We performed whole genome expression profiling
of RNA obtained from frontal cortex of clinically non-demented and
AD subjects to identify genes associated with brain aging and cognitive
decline. Genetic mapping information and biological function annotation
were incorporated to highlight genes of particular interest. The
candidate genes identified in this study were compared with those
from two other studies in different tissues to identify common underlying
transcriptional profiles. In addition to confirming sweeping transcriptomal
differences documented in previous studies of cognitive decline,
we present new evidence for up-regulation of actin-related processes
and down-regulation of translation, RNA processing and localization,
and vesicle-mediated transport in individuals with cognitive decline.},
issn = {0197-4580},
keywords = {Cognitive reserve, Cognitive decline, Alzheimer's disease, Healthy
brain aging, Gene expression profiling, Synaptic plasticity, Intersectin
1},
url = {http://www.sciencedirect.com/science/article/B6T09-4MK0HFP-3/2/16f5b077ebd689d93229b968e56d77f9}
}
@ARTICLE{Wilson2010,
author = {Wilson, Camella G. and Schupp, Michael and Burkhardt, Brant R. and
Wu, Jianmei and Young, Robert A. and Wolf, Bryan A.},
title = {Liver-Specific Overexpression of Pancreatic-Derived Factor (PANDER)
Induces Fasting Hyperglycemia in Mice},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {5174--5184},
number = {11},
month = nov,
abstract = {The pancreas-derived hormones, insulin and glucagon, are the two main
regulators of glucose homeostasis. However, their actions can be
modulated by the presence of other circulating factors including
cytokines. Pancreatic-derived factor (PANDER) is a novel cytokine-like
molecule secreted from the endocrine pancreas, but its biological
function is currently unknown. To address this, we employed adenoviral
gene delivery to develop a novel murine model of PANDER overexpression,
which we used to study PANDER's effect on glucose homeostasis. Although
serum metabolites in fed mice were unaffected by PANDER overexpression,
fasting glucose, insulin, and corticosterone levels were significantly
elevated. Additionally, PANDER-overexpressing mice displayed elevated
glucose and insulin levels during a glucose tolerance test, indicating
that glucose tolerance was impaired. However, there were no defects
in glucose-stimulated insulin secretion or peripheral insulin sensitivity.
Elevated transcription of hepatic gluconeogenic genes, PEPCK and
G6Pase accompanied the fasting hyperglycemia observed in PANDER-overexpressing
animals. Similarly, treatment of primary hepatocytes with PANDER-expressing
adenovirus or PANDER-enriched conditioned medium elevated gluconeogenic
gene expression and glucose output. PANDER treatment also resulted
in higher levels of Ser133-phosphorylated cAMP-response element-binding
protein in hepatocytes stimulated with 8-bromo-cAMP and dexamethasone
and higher levels of intracellular cAMP upon stimulation with forskolin.
In summary, we provide the first report that identifies PANDER as
a regulator of hepatic glucose metabolism, where it serves as a novel
factor that amplifies hepatic cAMP and cAMP-response element-binding
protein signaling to induce gluconeogenic gene expression and glucose
output.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/11/5174}
}
@ARTICLE{Wilson2006,
author = {Wilson, C L and Sims, A H and Howell, A and Miller, C J and Clarke,
R B},
title = {Effects of oestrogen on gene expression in epithelium and stroma
of normal human breast tissue},
journal = {Endocr. Relat. Cancer},
year = {2006},
volume = {13},
pages = {617--628},
number = {2},
month = jun,
abstract = {Oestrogen (E) is essential for normal and cancer development in the
breast, while anti-oestrogens have been shown to reduce the risk
of the disease. However, little is known about the effect of E on
gene expression in the normal human breast, particularly when the
epithelium and stroma are intact. Previous expression profiles of
the response to E have been performed on tumour cell lines, in the
absence of stroma. We investigated gene expression in normal human
breast tissue transplanted into 9-10-week-old female athymic nude
(Balb/c nu/nu) mice. After 2 weeks, when epithelial proliferation
is minimal, one-third of the mice were treated with 17{beta}-oestradiol
(E2) to give human luteal-phase levels in the mouse, which we have
previously shown to induce maximal epithelial cell proliferation.
RNA was isolated from treated and untreated mice, labelled and hybridized
to Affymetrix HG-U133A (human) GeneChips. Gene expression levels
were generated using BioConductor implementations of the RMA and
MAS5 algorithms. E2 treatment was found to represent the largest
source of variation in gene expression and cross-species hybridization
of mouse RNA from xenograft samples was demonstrated to be negligible.
Known E2-responsive genes (such as TFF1 and AREG), and genes thought
to be involved in breast cancer metastasis (including mammoglobin,
KRT19 and AGR2), were upregulated in response to E treatment. Genes
known to be co-expressed with E receptor {alpha} in breast cancer
cell lines and tumours were both upregulated (XBP-1 and GREB1) and
downregulated (RARRES1 and GATA3). In addition, genes that are normally
expressed in the myoepithelium and extracellular matrix that maintain
the tissue microenvironment were also differentially expressed. This
suggests that the response to oestrogen in normal breast is highly
dependent upon epithelial-stromal/myoepithelial interactions which
maintain the tissue microenvironment during epithelial cell proliferation.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/13/2/617}
}
@ARTICLE{Wilson2011,
author = {Wilson, D.J. and Justice-Allen, A. and Goodell, G. and Baldwin, T.J.
and Skirpstunas, R.T. and Cavender, K.B.},
title = {Risk of Mycoplasma bovis transmission from contaminated sand bedding
to naive dairy calves},
journal = {Journal of Dairy Science},
year = {2011},
volume = {94},
pages = {1318--1324},
number = {3},
month = mar,
abstract = {The objective of this study was to evaluate the possible transmission
of Mycoplasma bovis from positive sand bedding to naïve dairy calves.
Twelve preweaned Holstein bull calves were blocked in pairs and randomly
assigned as unexposed controls (n = 6) bedded with control sand,
or exposed calves (n = 6) bedded with sand previously positive for
M. bovis at a dairy farm. Bedding sand was cultured weekly. Nasal
and ear swabs and sera were collected weekly, tracheal swabs were
collected monthly, and by the end of the 105-d study, all calves
were euthanized (n = 10) or died (n = 2). Sera were tested for M.
bovis-specific antibody. Mycoplasma spp. culture was performed on
nasal and ear swabs; culture and a PCR differentiating multiple Mycoplasma
spp. were performed on postmortem samples of lung, retropharyngeal
lymph node, and trachea from each calf. A complete necropsy also
was performed. During 6 wk, mycoplasma concentration in exposed group
sand was between 200 and 32,000 cfu/g. All 166 tracheal swabs, nasal
and ear swabs, and postmortem tests from all calves were negative
for mycoplasma. All 94 sera were negative for M. bovis-specific antibody.
No gross pathology suggestive of mycoplasma disease was detected.
The probability of mycoplasma detection, if an exposed calf had become
infected 4 wk after exposure, ranged between 97 and 99% depending
on time of exposure for individual calves. There was no evidence
that sand bedding contaminated with M. bovis might serve as a source
of transmission to naïve dairy calves.},
issn = {0022-0302},
keywords = {bedding, dairy cattle, environment, mycoplasma},
url = {http://www.sciencedirect.com/science/article/pii/S0022030211000865}
}
@ARTICLE{Wilson2006a,
author = {Wilson, Paul A. and Gardner, Scott D. and Lambie, Natalie M. and
Commans, Stephane A. and Crowther, Daniel J.},
title = {Characterization of the human patatin-like phospholipase family},
journal = {J. Lipid Res.},
year = {2006},
volume = {47},
pages = {1940--1949},
number = {9},
month = sep,
abstract = {Several publications have described biological roles for human patatin-like
phospholipases (PNPLAs) in the regulation of adipocyte differentiation.
Here, we report on the characterization and expression profiling
of 10 human PNPLAs. A variety of bioinformatics approaches were used
to identify and characterize all PNPLAs encoded by the human genome.
The genes described represent a divergent family, most with a highly
conserved ortholog in several mammalian species. In silico characterization
predicts that two of the genes function as integral membrane proteins
and are regulated by cAMP/cGMP. A structurally guided protein alignment
of the patatin-like domain identifies a number of conserved residues
in all family members. Quantitative PCR was used to determine the
expression profile of each family member. Affymetrix-based profiling
of a human preadipocyte cell line identified several members that
are differentially regulated during cell differentiation. Cumulative
data suggest that patatin-like genes normally expressed at very low
levels are induced in response to environmental signals. Given the
observed conservation of the patatin fold and lipase motif in all
human PNPLAs, a single nomenclature to describe the PNPLA family
is proposed.},
url = {http://www.jlr.org/cgi/content/abstract/47/9/1940}
}
@ARTICLE{Wilson2009,
author = {Wilson, Pip B. and Estavillo, Gonzalo M. and Field, Katie J. and
Pornsiriwong, Wannarat and Carroll, Adam J. and Howell, Katharine
A. and Woo, Nick S. and Lake, Janice A. and Smith, Steven M. and
Harvey Millar, A. and Von Caemmerer, Susanne and Pogson, Barry J.},
title = {The nucleotidase/phosphatase SAL1 is a negative regulator of drought
tolerance in Arabidopsis},
journal = {The Plant Journal},
year = {2009},
volume = {58},
pages = {299--317},
number = {2},
abstract = {Summary An Arabidopsis thaliana drought-tolerant mutant, altered expression
of APX2 (alx8), has constitutively increased abscisic acid (ABA)
content, increased expression of genes responsive to high light stress
and is reported to be drought tolerant. We have identified alx8 as
a mutation in SAL1, an enzyme that can dephosphorylate dinucleotide
phosphates or inositol phosphates. Previously identified mutations
in SAL1, including fiery (fry1-1), were reported as being more sensitive
to drought imposed by detachment of rosettes. Here we demonstrate
that alx8, fry1-1 and a T-DNA insertional knockout allele all have
markedly increased resistance to drought when water is withheld from
soil-grown intact plants. Microarray analysis revealed constitutively
altered expression of more than 1800 genes in both alx8 and fry1-1.
The up-regulated genes included some characterized stress response
genes, but few are inducible by ABA. Metabolomic analysis revealed
that both mutants exhibit a similar, dramatic reprogramming of metabolism,
including increased levels of the polyamine putrescine implicated
in stress tolerance, and the accumulation of a number of unknown,
potential osmoprotectant carbohydrate derivatives. Under well-watered
conditions, there was no substantial difference between alx8 and
Col-0 in biomass at maturity; plant water use efficiency (WUE) as
measured by carbon isotope discrimination; or stomatal index, morphology
or aperture. Thus, SAL1 acts as a negative regulator of predominantly
ABA-independent and also ABA-dependent stress response pathways,
such that its inactivation results in altered osmoprotectants, higher
leaf relative water content and maintenance of viable tissues during
prolonged water stress.},
issn = {1365-313X},
keywords = {drought, water use efficiency, SAL1, Arabidopsis, signal transduction,
phosphoinositides (PI)},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2008.03780.x}
}
@ARTICLE{Wilson2011a,
author = {R. Alan Wilson and Janelle M. Wright and William de Castro-Borges
and Sophie J. Parker-Manuel and Adam A. Dowle and Peter D. Ashton
and Neil D. Young and Robin B. Gasser and Terry W. Spithill},
title = {Exploring the Fasciola hepatica tegument proteome},
journal = {International Journal for Parasitology},
year = {2011},
volume = {41},
pages = {1347 - 1359},
number = {13–14},
abstract = {The surface tegument of the liver fluke Fasciola hepatica is a syncytial
cytoplasmic layer bounded externally by a plasma membrane and covered
by a glycocalyx, which constitutes the interface between the parasite
and its ruminant host. The tegument’s interaction with the immune
system during the fluke’s protracted migration from the gut lumen
through the peritoneal cavity and liver parenchyma to the lumen of
the bile duct, plays a key role in the fluke’s establishment or
elimination. However, little is known about proteins of the tegument
surface or its secretions. We applied techniques developed for the
blood fluke, Schistosoma mansoni, to enrich a tegument surface membrane
preparation and analyse its composition by tandem mass spectrometry
using new transcript databases for F. hepatica. We increased the
membrane and secretory pathway components of the final preparation
to ∼30%, whilst eliminating contaminating proteases. We identified
a series of proteins or transcripts shared with the schistosome tegument
including annexins, a tetraspanin, carbonic anhydrase and an orthologue
of a host protein (CD59) that inhibits complement fixation. Unique
to F. hepatica, we also found proteins with lectin, cubulin and von
Willebrand factor domains plus 10 proteins with leader sequences
or transmembrane helices. Many of these surface proteins are potential
vaccine candidates. We were hampered in collecting tegument secretions
by the propensity of liver flukes, unlike blood flukes, to vomit
their gut contents. We analysed both the ‘vomitus’ and a second
supernatant released from haematin-depleted flukes. We identified
many proteases, some novel, as well as a second protein with a von
Willebrand factor domain. This study demonstrates that components
of the tegumental surface of F. hepatica can be defined using proteomic
approaches, but also indicates the need to prevent vomiting if tegument
secretions are to be characterised.},
doi = {10.1016/j.ijpara.2011.08.003},
issn = {0020-7519},
keywords = {Fasciola hepatica},
url = {http://www.sciencedirect.com/science/article/pii/S0020751911002426}
}
@ARTICLE{Wilson2009a,
author = {Wilson, Scott G and Jones, Michelle R and Mullin, Ben H and Dick,
Ian M and Richards, J Brent and Pastinen, Tomi M and Grundberg, Elin
and Ljunggren, Östen and Surdulescu, Gabriela L and Dudbridge, Frank
and Elliott, Katherine S and Cervino, Alessandra CL and Spector,
Timothy D and Prince, Richard L},
title = {Common Sequence Variation in FLNB Regulates Bone Structure in Women
in the General Population and FLNB mRNA Expression in Osteoblasts
In Vitro},
journal = {J Bone Miner Res},
year = {2009},
volume = {24},
pages = {1989--1997},
number = {12},
abstract = {Abstract 10.1359/jbmr.090530.abs Previous data from our group indicate
that BMD is linked to chromosome 3p14–p21. Because the filamin
B (FLNB gene resides in this region, is the cause of skeletal dysplasias,
and was identified among the top genes in our bioinformatics analysis,
we hypothesized a role for FLNB in the regulation of bone structure
in the general population. Using a tag single nucleotide polymorphism
(SNP) approach, a family study of 767 female sibs in which the 3p14–p21
linkage with BMD was previously shown was examined. FLNB variants
showing a BMD association were tested in two additional data sets,
a study of 1085 UK female twins and a population study (CAIFOS) of
1315 Australian women. Genotype-expression studies were performed
in 96 human osteoblast lines to examine the variants in vitro. rs7637505,
rs9822918, rs2177153, and rs2001972 showed association with femoral
neck (p = 0.0002–0.02) in the family-based study. The twin study
provided further support for an association between rs7637505 and
femoral neck and spine BMD (p = 0.02–0.03). The CAIFOS study further
suggested an association between rs2177153 and rs9822918 and femoral
neck BMD (p = 0.004–0.03). Prevalent fractures were increased in
carriers of the A allele of rs2177153 (p = 0.009). In vitro studies
showed association between rs11130605, itself in strong LD with rs7637505,
and FLNB mRNA expression. These findings suggest common variants
in FLNB have effects on bone structure in women. Although the location
of variants having effects is not entirely consistent, variation
at the 5′ end of the gene may reflect effects on levels of FLNB
transcription efficiency.},
issn = {1523-4681},
keywords = {filamin B, BMD, single nucleotide polymorphism, osteoporosis, fracture},
publisher = {John Wiley and Sons and The American Society for Bone and Mineral
Research (ASBMR)},
url = {http://dx.doi.org/10.1359/jbmr.090530}
}
@ARTICLE{Wilson2007,
author = {Wilson, Sam J. and Tsao, Edward H. and Webb, Benjamin L. J. and Ye,
Hongtao and Dalton-Griffin, Lucy and Tsantoulas, Christoforos and
Gale, Catherine V. and Du, Ming-Qing and Whitehouse, Adrian and Kellam,
Paul},
title = {X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated
Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation
to KSHV Reactivation from Latency},
journal = {J. Virol.},
year = {2007},
volume = {81},
pages = {13578--13586},
number = {24},
month = dec,
abstract = {Reactivation of lytic replication from viral latency is a defining
property of all herpesviruses. Despite this, the authentic physiological
cues for the latent-lytic switch are unclear. Such cues should ensure
that viral lytic replication occurs under physiological conditions,
predominantly in sites which facilitate transmission to permissive
uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated
herpesvirus (KSHV) is associated with the B-cell neoplasm primary
effusion lymphoma (PEL), in which the virus remains latent. We have
previously shown that PEL cells have the gene expression profile
and immunophenotype of cycling preplasma cells (plasmablasts). Here,
we show that the highly active spliced isoform of plasma cell transcription
factor X box binding protein 1 (XBP-1s) is a lytic switch for KSHV.
XBP-1s is normally absent in PEL, but the induction of endoplasmic
reticulum stress leads to XBP-1s generation, plasma cell-like differentiation,
and lytic reactivation of KSHV. XBP-1s binds to and activates the
KSHV immediate-early gene ORF50 and synergizes with the ORF50 gene
product RTA to induce a full lytic cycle. These data suggest that
KSHV remains latent until B-cell terminal differentiation into plasma
cells, the transcriptional environment of which provides the physiological
"lytic switch" through XBP-1s. This links B-cell terminal differentiation
to KSHV lytic reactivation.},
url = {http://jvi.asm.org/cgi/content/abstract/81/24/13578}
}
@ARTICLE{Wilson2009b,
author = {Wilson, Vickie S. and Lambright, Christy R. and Furr, Johnathan R.
and Howdeshell, Kembra L. and Earl Gray Jr., L.},
title = {The herbicide linuron reduces testosterone production from the fetal
rat testis during both in utero and in vitro exposures},
journal = {Toxicology Letters},
year = {2009},
volume = {186},
pages = {73--77},
number = {2},
month = apr,
abstract = {In utero exposure to linuron, an urea-based herbicide, results in
a pattern of malformations of androgen-dependent tissues in adult
male rat offspring resembling that produced by some phthalate esters
which are known to decrease fetal testosterone production. This study
investigated the impact of in utero linuron treatment on fetal testis
gene expression and testosterone production. Timed-pregnant Sprague
Dawley rats were administered corn oil vehicle, 12.5, 25, 50 or 75 mg
linuron/day/kg orally from GD13 to 18. Ex vivo testosterone (T) production
was significantly decreased at 50 and 75 mg/kg when analyzed on a
per litter basis. Unlike the phthalate esters, linuron treatment
did not affect insl3, cyp17a, cyp11a or StAR mRNA expression. Control
GD18 fetal testes were then incubated with increasing concentrations
of linuron (1-300 [mu]M) to evaluate if linuron inhibited T production
in vitro. T production was significantly reduced at 30 [mu]M and
above. Progesterone production was not affected in any of the studies
indicating that linuron directly inhibited testosterone production
in the absence of cytotoxicity. These results indicate the malformations
induced by linuron and phthalate esters in male offspring are similar
because both reduce fetal T levels during the critical period of
sex differentiation but suggest that the mechanisms differ.},
issn = {0378-4274},
keywords = {Linuron, Testosterone production, Sex differentiation, Endocrine disruption,
Fetal, Rat},
url = {http://www.sciencedirect.com/science/article/B6TCR-4VBDKFX-1/2/5f757808000c830ff5d95462bcbda26b}
}
@ARTICLE{Wilting2008,
author = {Wilting, Saskia M. and de Wilde, Jillian and Meijer, Chris J. L.
M. and Berkhof, Johannes and Yi, Yajun and van Wieringen, Wessel
N. and Braakhuis, Boudewijn J. M. and Meijer, Gerrit A. and Ylstra,
Bauke and Snijders, Peter J. F. and Steenbergen, Renske D. M.},
title = {Integrated genomic and transcriptional profiling identifies chromosomal
loci with altered gene expression in cervical cancer},
journal = {Genes Chromosom. Cancer},
year = {2008},
volume = {47},
pages = {890--905},
number = {10},
abstract = {Abstract 10.1002/gcc.20590.abs For a better understanding of the consequences
of recurrent chromosomal alterations in cervical carcinomas, we integrated
genome-wide chromosomal and transcriptional profiles of 10 squamous
cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal controls.
Previous genomic profiling showed that gains at chromosome arms 1q,
3q, and 20q as well as losses at 8q, 10q, 11q, and 13q were common
in cervical carcinomas. Altered regions spanned multiple megabases,
and the extent to which expression of genes located there is affected
remains unclear. Expression analysis of these previously chromosomally
profiled carcinomas yielded 83 genes with significantly differential
expression between carcinomas and normal epithelium. Application
of differential gene locus mapping (DIGMAP) analysis and the array
CGH expression integration tool (ACE-it) identified hotspots within
large chromosomal alterations in which gene expression was altered
as well. Chromosomal gains of the long arms of chromosome 1, 3, and
20 resulted in increased expression of genes located at 1q32.1-32.2,
3q13.32-23, 3q26.32-27.3, and 20q11.21-13.33, whereas a chromosomal
loss of 11q22.3-25 was related to decreased expression of genes located
in this region. Overexpression of DTX3L, PIK3R4, ATP2C1, and SLC25A36,
all located at 3q21.1-23 and identified by DIGMAP, ACE-it or both,
was confirmed in an independent validation sample set consisting
of 12 SCCs and 13 normal ectocervical samples. In conclusion, integrated
chromosomal and transcriptional profiling identified chromosomal
hotspots at 1q, 3q, 11q, and 20q with altered gene expression within
large commonly altered chromosomal regions in cervical cancer. ©
2008 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20590}
}
@ARTICLE{Wiltshire2011,
author = {Wiltshire, Sean A. and Leiva-Torres, Gabriel Andre and Vidal, Silvia
M.},
title = {Quantitative Trait Locus Analysis, Pathway Analysis, and Consomic
Mapping Show Genetic Variants of Tnni3k, Fpgt, or H28 Control Susceptibility
to Viral Myocarditis},
journal = {J. Immunol.},
year = {2011},
volume = {186},
pages = {6398--6405},
number = {11},
month = jun,
abstract = {Coxsackievirus B3 (CVB3) infection is the most common cause of viral
myocarditis. The pathogenesis of viral myocarditis is strongly controlled
by host genetic factors. Although certain indispensable components
of immunity have been identified, the genes and pathways underlying
natural variation between individuals remain unclear. Previously,
we isolated the viral myocarditis susceptibility 1 (Vms1) locus on
chromosome 3, which influences pathogenesis. We hypothesized that
confirmation and further study of Vms1 controlling CVB3-mediated
pathology, combined with pathway analysis and consomic mapping approaches,
would elucidate both pathological and protective mechanisms accounting
for natural variation in response to CVB3 infection. Vms1 was originally
mapped to chromosome 3 using a segregating cross between susceptible
A/J and resistant B10.A mice. To validate Vms1, C57BL/6J-Chr 3A/NaJ
(a chromosome substitution strain that carries a diploid A/J chromosome
3) were used to replicate susceptibility compared with resistant
C57BL/6J (B6). A second segregating F2 cross was generated between
these, confirming both the localization and effects of Vms1. Microarray
analysis of the four strains (A/J, B10.A, C57BL/6J, and C57BL/6J-Chr
3A/NaJ) illuminated a core program of response to CVB3 in all strains
that is comprised mainly of IFN-stimulated genes. Microarray analysis
also revealed strain-specific differential expression programs and
genes that may be prognostic or diagnostic of susceptibility to CVB3
infection. A combination of analyses revealed very strong evidence
for the existence and location of Vms1. Differentially expressed
pathways were identified by microarray, and candidate gene analysis
revealed Fpgt, H28, and Tnni3k as likely candidates for Vms1.},
comment = {10.4049/jimmunol.1100159},
url = {http://www.jimmunol.org/cgi/content/abstract/186/11/6398}
}
@ARTICLE{Wimberger2008,
author = {Wimberger, Pauline and Hauch, Siegfried and Lustig, Michael and Kimmig,
Rainer and Kasimir-Bauer, Sabine},
title = {Detection and molecular profiling of circulating tumor cells in patients
with primary ovarian cancer.},
journal = {AACR Meeting Abstracts},
year = {2008},
volume = {2008},
pages = {965--},
number = {1_Annual_Meeting},
month = apr,
url = {http://www.aacrmeetingabstracts.org}
}
@ARTICLE{Windisch2011,
author = {Windisch, Heidrun Sigrid and Kathover, Raphaela and Portner, Hans-Otto
and Frickenhaus, Stephan and Lucassen, Magnus},
title = {Thermal acclimation in Antarctic fish: transcriptomic profiling of
metabolic pathways},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2011},
volume = {301},
pages = {R1453-1466},
number = {5},
abstract = {It is widely accepted that adaptation to the extreme cold has evolved
at the expense of high thermal sensitivity. However, recent studies
have demonstrated significant capacities for warm acclimation in
Antarctic fishes. Here, we report on hepatic metabolic reorganization
and its putative molecular background in the Antarctic eelpout (Pachycara
brachycephalum) during warm acclimation to 5{degrees}C over 6 wk.
Elevated capacities of cytochrome c oxidase suggest the use of warm
acclimation pathways different from those in temperate fish. The
capacity of this enzyme rose by 90%, while citrate synthase (CS)
activity fell by 20% from the very beginning. The capacity of lipid
oxidation by hydroxyacyl-CoA dehydrogenase remained constant, whereas
phosphoenolpyruvate carboxykinase as a marker for gluconeogenesis
displayed 40% higher activities. These capacities in relation to
CS indicate a metabolic shift from lipid to carbohydrate metabolism.
The finding was supported by large rearrangements of the related
transcriptome, both functional genes and potential transcription
factors. A multivariate analysis (canonical correspondence analyses)
of various transcripts subdivided the incubated animals in three
groups, one control group and two responding on short and long timescales,
respectively. A strong dichotomy in the expression of peroxisome
proliferator-activated receptors-1 and -{beta} receptors was most
striking and has not previously been reported. Altogether, we identified
a molecular network, which responds sensitively to warming beyond
the realized ecological niche. The shift from lipid to carbohydrate
stores and usage may support warm hardiness, as the latter sustain
anaerobic metabolism and may prepare for hypoxemic conditions that
would develop upon warming beyond the present acclimation temperature.},
doi = {10.1152/ajpregu.00158.2011},
eprint = {http://ajpregu.physiology.org/cgi/reprint/301/5/R1453.pdf},
url = {http://ajpregu.physiology.org/cgi/content/abstract/301/5/R1453}
}
@ARTICLE{Wingate2009,
author = {Wingate, Kyra V. and Torres, Sheila M. and Silverstein, Kevin A.
T. and Hendrickson, Julie A. and Rutherford, Mark S.},
title = {Expression of endogenous antimicrobial peptides in normal canine
skin},
journal = {Veterinary Dermatology},
year = {2009},
volume = {20},
pages = {19--26},
number = {1},
abstract = {Abstract The cutaneous barrier contains small, cationic antimicrobial
peptides that participate in the innate immunity against a wide variety
of pathogens. Despite their immune importance, knowledge of canine
defensins and their expression is limited primarily to testicular
tissue and their relation to coat colour. Studies have shown that
the absence of these antimicrobial peptides contribute to increased
secondary infections in humans. The goals of this study were to identify
defensin and protease inhibitor peptide genes by performing a computer-based
iterative screen of the canine genome and to determine whether antimicrobial
peptides are expressed in normal canine skin. Reverse transcription-polymerase
chain reaction (RT-PCR) was used to test for the expression of several
antimicrobial peptides in the skin of five normal dogs. RNA from
testis was used for comparison. The iterative screen identified 65
putative antimicrobial peptide genes on nine chromosomes, the majority
clustered on chromosomes 16 and 24. Amplification of normal canine
skin cDNAs demonstrated expression of antimicrobial peptide genes
in five different body sites. These findings will provide a tool
for future studies examining the association between antimicrobial
gene expression and cutaneous immunity in dogs.},
issn = {1365-3164},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-3164.2008.00707.x}
}
@ARTICLE{Wingrove2008,
author = {Wingrove, James A. and Daniels, Susan E. and Sehnert, Amy J. and
Tingley, Whittemore and Elashoff, Michael R. and Rosenberg, Steven
and Buellesfeld, Lutz and Grube, Eberhard and Newby, L. Kristin and
Ginsburg, Geoffrey S. and Kraus, William E.},
title = {Correlation of Peripheral-Blood Gene Expression With the Extent of
Coronary Artery Stenosis},
journal = {Circ Cardiovasc Genet},
year = {2008},
volume = {1},
pages = {31--38},
number = {1},
month = oct,
abstract = {Background-- The molecular pathophysiology of coronary artery disease
(CAD) includes cytokine release and a localized inflammatory response
within the vessel wall. The extent to which CAD and its severity
is reflected by gene expression in circulating cells is unknown.
Methods and Results-- From an initial coronary catheterization cohort
we identified 41 patients, comprising 27 cases with angiographically
significant CAD and 14 controls without coronary stenosis. Whole-genome
microarray analysis performed on peripheral-blood mononuclear cells
yielded 526 genes with >1.3-fold differential expression (P<0.05)
between cases and controls. Real-time polymerase chain reaction on
106 genes (the 50 most significant microarray genes and 56 additional
literature genes) in an independent subset of 95 patients (63 cases,
32 controls) from the same cohort yielded 14 genes (P<0.05) that
independently discriminated CAD state in a multivariable analysis
that included clinical and demographic factors. From an independent
second catheterization cohort, 215 patients were selected for real-time
polymerase chain reaction-based replication. A case:control subset
of 107 patients (86 cases, 21 controls) replicated 11 of the 14 multivariably
significant genes from the first cohort. An analysis of the 14 genes
in the entire set of 215 patients demonstrated that gene expression
was proportional to maximal coronary artery stenosis (P<0.001 by
ANOVA). Conclusions-- Gene expression in peripheral-blood cells reflects
the presence and extent of CAD in patients undergoing angiography.},
url = {http://circgenetics.ahajournals.org/cgi/content/abstract/1/1/31}
}
@ARTICLE{Winn2009,
author = {Winn, Virginia D. and Gormley, Matthew and Paquet, Agnes C. and Kjaer-Sorensen,
Kasper and Kramer, Anita and Rumer, Kristen K. and Haimov-Kochman,
Ronit and Yeh, Ru-Fang and Overgaard, Michael T. and Varki, Ajit
and Oxvig, Claus and Fisher, Susan J.},
title = {Severe Preeclampsia-Related Changes in Gene Expression at the Maternal-Fetal
Interface Include Sialic Acid-Binding Immunoglobulin-Like Lectin-6
and Pappalysin-2},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {452--462},
number = {1},
month = jan,
abstract = {Preeclampsia (PE), which affects 4-8% of human pregnancies, causes
significant maternal and neonatal morbidity and mortality. Within
the basal plate, placental cytotrophoblasts (CTBs) of fetal origin
invade the uterus and extensively remodel the maternal vasculature.
In PE, CTB invasion is often shallow, and vascular remodeling is
rudimentary. To better understand possible causes, we conducted a
global analysis of gene expression at the maternal-fetal interface
in placental samples from women with PE (n = 12; 24-36 wk) vs. samples
from women who delivered due to preterm labor with no evidence of
infection (n = 11; 24-36 wk), a condition that our previous work
showed is associated with normal CTB invasion. Using the HG-U133A&B
Affymetrix GeneChip platform, and statistical significance set at
log odds-ratio of B >0, 55 genes were differentially expressed in
PE. They encoded proteins previously associated with PE [e.g. Flt-1
(vascular endothelial growth factor receptor-1), leptin, CRH, and
inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin
6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2),
a protease that cleaves IGF-binding proteins]. We used quantitative
PCR to validate the expression patterns of a subset of the genes.
At the protein level, we confirmed PE-related changes in the expression
of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts.
Notably, Siglec-6 placental expression is uniquely human, as is spontaneous
PE. The functional significance of these novel observations may provide
new insights into the pathogenesis of PE, and assaying the circulating
levels of these proteins could have clinical utility for predicting
and/or diagnosing PE.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/1/452}
}
@ARTICLE{Winn2007,
author = {Winn, Virginia D. and Haimov-Kochman, Ronit and Paquet, Agnes C.
and Yang, Y. Jean and Madhusudhan, M. S. and Gormley, Matthew and
Feng, Kui-Tzu V. and Bernlohr, David A. and McDonagh, Susan and Pereira,
Lenore and Sali, Andrej and Fisher, Susan J.},
title = {Gene Expression Profiling of the Human Maternal-Fetal Interface Reveals
Dramatic Changes between Midgestation and Term},
journal = {Endocrinology},
year = {2007},
volume = {148},
pages = {1059--1079},
number = {3},
month = mar,
abstract = {Human placentation entails the remarkable integration of fetal and
maternal cells into a single functional unit. In the basal plate
region (the maternal-fetal interface) of the placenta, fetal cytotrophoblasts
from the placenta invade the uterus and remodel the resident vasculature
and avoid maternal immune rejection. Knowing the molecular bases
for these unique cell-cell interactions is important for understanding
how this specialized region functions during normal pregnancy with
implications for tumor biology and transplantation immunology. Therefore,
we undertook a global analysis of the gene expression profiles at
the maternal-fetal interface. Basal plate biopsy specimens were obtained
from 36 placentas (14-40 wk) at the conclusion of normal pregnancies.
RNA was isolated, processed, and hybridized to HG-U133A&B Affymetrix
GeneChips. Surprisingly, there was little change in gene expression
during the 14- to 24-wk interval. In contrast, 418 genes were differentially
expressed at term (37-40 wk) as compared with midgestation (14-24
wk). Subsequent analyses using quantitative PCR and immunolocalization
approaches validated a portion of these results. Many of the differentially
expressed genes are known in other contexts to be involved in differentiation,
motility, transcription, immunity, angiogenesis, extracellular matrix
dissolution, or lipid metabolism. One sixth were nonannotated or
encoded hypothetical proteins. Modeling based on structural homology
revealed potential functions for 31 of these proteins. These data
provide a reference set for understanding the molecular components
of the dialogue taking place between maternal and fetal cells in
the basal plate as well as for future comparisons of alterations
in this region that occur in obstetric complications.},
url = {http://endo.endojournals.org/cgi/content/abstract/148/3/1059}
}
@ARTICLE{Winnepenninckx2006,
author = {Winnepenninckx, Veronique and Lazar, Vladimir and Michiels, Stefan
and Dessen, Philippe and Stas, Marguerite and Alonso, Soledad R.
and Avril, Marie-Francoise and Ortiz Romero, Pablo L. and Robert,
Thomas and Balacescu, Ovidiu and Eggermont, Alexander M. M. and Lenoir,
Gilbert and Sarasin, Alain and Tursz, Thomas and van den Oord, Joost
J. and Spatz, Alain},
title = {Gene Expression Profiling of Primary Cutaneous Melanoma and Clinical
Outcome},
journal = {J Natl Cancer Inst},
year = {2006},
volume = {98},
pages = {472--482},
number = {7},
month = apr,
abstract = {Background: Gene expression profiling data for human primary cutaneous
melanomas are scarce because of the lack of retrospective collections
of frozen tumors. To identify differentially expressed genes that
may be involved in melanoma progression and prognosis, we investigated
the relationship between gene expression profiles and clinical outcome
in a cohort of patients with primary melanoma. Methods: Labeled complementary
RNA (cRNA) from each tissue sample was hybridized to a pangenomic
44K 60-mer oligonucleotide microarray. Class comparison and class
prediction analyses were performed to identify genes whose expression
in primary melanomas was associated with 4-year distant metastasis-free
survival among 58 patients with at least 4 years of follow-up, distant
metastasis, or death. Results were validated immunohistochemically
at the protein level in 176 independent primary melanomas from patients
with a median clinical follow-up of 8.5 years. Survival was analyzed
with a Cox multivariable model and stratified log-rank test. All
statistical tests were two-sided. Results: We identified 254 genes
that were associated with distant metastasis-free survival of patients
with primary melanoma. These 254 genes include genes involved in
activating DNA replication origins, such as minichromosome maintenance
genes and geminin. Twenty-three of these genes were studied at the
protein level; expression of five (MCM4, P = .002; MCM3, P = .030;
MCM6, P = .004; KPNA2, P = .021; and geminin, P = .004) was statistically
significantly associated with overall survival in the validation
set. In a multivariable Cox model adjusted for tumor thickness, ulceration,
age, and sex, expression of MCM4 (hazard ratio [HR] of death = 4.04,
95% confidence interval [CI] = 1.39 to 11.76; P = .010) and MCM6
(HR of death = 7.42, 95% CI = 1.99 to 27.64; P = .003) proteins was
still statistically significantly associated with overall survival.
Conclusion: We identified 254 genes whose expression was associated
with metastatic dissemination of cutaneous melanomas. These genes
may shed light on the molecular mechanisms underlying poor prognosis
in melanoma patients.},
url = {http://jnci.oxfordjournals.org/cgi/content/abstract/98/7/472}
}
@ARTICLE{Winnes2007,
author = {Winnes, Marta and Mölne, Lena and Suurküla, Mart and Andrén, Ywonne
and Persson, Fredrik and Enlund, Fredrik and Stenman, Göran},
title = {Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants
of cutaneous hidradenomas},
journal = {Genes Chromosom. Cancer},
year = {2007},
volume = {46},
pages = {559--563},
number = {6},
abstract = {Abstract 10.1002/gcc.20440.abs Fusion of the CREB regulated transcription
coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator
MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas
of salivary and bronchial glands. The CRTC1–MAML2 fusion protein
acts by inducing transcription of cAMP/CREB target genes, and this
activity is crucial for the transforming properties of the protein.
Here we show that the CRTC1–MAML2 gene fusion is also frequent
in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed
that hidradenomas are genetically heterogeneous, and that 10 of the
20 tumors analyzed (50%) contained the CRTC1–MAML2 gene fusion
and expressed the resulting fusion transcript. Immunohistochemical
analysis demonstrated expression of the fusion protein in the majority
of tumor cells, including clear cells, poroid cells, and cells with
epidermoid and ductal differentiation. In addition, we could show
that all fusion-positive tumors were morphologically distinguished
by the presence of more or less abundant areas of clear cells whereas
all fusion-negative tumors lacked clear cells. Our findings thus
demonstrate that the CRTC1–MAML2 gene fusion is frequent in hidradenomas
and is associated with clear cell variants of this tumor. Taken together,
the present and previous observations indicate that the CRTC1–MAML2
fusion is etiologically linked to benign and low-grade malignant
tumors originating from diverse exocrine glands rather than being
linked to a separate tumor entity. © 2007 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20440}
}
@ARTICLE{Winnicka2010,
author = {Winnicka, Beata and O'Conor, Catherine and Schacke, Wolfgang and
Vernier, Kaitlyn and Grant, Christina L. and Fenteany, Fiona Hall
and Pereira, Flavia E. and Liang, Brannen and Kaur, Anupinder and
Zhao, Ran and Montrose, David C. and Rosenberg, Daniel W. and Aguila,
Hector L. and Shapiro, Linda H.},
title = {CD13 is dispensable for normal hematopoiesis and myeloid cell functions
in the mouse},
journal = {J. Leukoc. Biol.},
year = {2010},
volume = {88},
pages = {347--359},
number = {2},
month = aug,
abstract = {The robust and consistent expression of the CD13 cell surface marker
on very early as well as differentiated myeloid hematopoietic cells
has prompted numerous investigations seeking to define roles for
CD13 in myeloid cells. To address the function of myeloid CD13 directly,
we created a CD13 null mouse and assessed the responses of purified
primary macrophages or DCs from WT and CD13 null animals in cell
assays and inflammatory disease models, where CD13 has been implicated
previously. We find that mice lacking CD13 develop normally with
normal hematopoietic profiles except for an increase in thymic but
not peripheral T cell numbers. Moreover, in in vitro assays, CD13
appears to be largely dispensable for the aspects of phagocytosis,
proliferation, and antigen presentation that we tested, although
we observed a slight decrease in actin-independent erythrocyte uptake.
However, in agreement with our published studies, we show that lack
of monocytic CD13 completely ablates anti-CD13-dependent monocyte
adhesion to WT endothelial cells. In vivo assessment of four inflammatory
disease models showed that lack of CD13 has little effect on disease
onset or progression. Nominal alterations in gene expression levels
between CD13 WT and null macrophages argue against compensatory mechanisms.
Therefore, although CD13 is highly expressed on myeloid cells and
is a reliable marker of the myeloid lineage of normal and leukemic
cells, it is not a critical regulator of hematopoietic development,
hemostasis, or myeloid cell function.},
url = {http://www.jleukbio.org/cgi/content/abstract/88/2/347}
}
@ARTICLE{Winrow2010,
author = {Winrow, Christopher J. and Tanis, Keith Q. and Reiss, Duane R. and
Rigby, Alison M. and Uslaner, Jason M. and Uebele, Victor N. and
Doran, Scott M. and Fox, Steven V. and Garson, Susan L. and Gotter,
Anthony L. and Levine, David M. and Roecker, Anthony J. and Coleman,
Paul J. and Koblan, Kenneth S. and Renger, John J.},
title = {Orexin receptor antagonism prevents transcriptional and behavioral
plasticity resulting from stimulant exposure},
journal = {Neuropharmacology},
year = {2010},
volume = {58},
pages = {185--194},
number = {1},
month = jan,
abstract = {Orexin is a key neurotransmitter of central arousal and reward circuits
in the CNS. Two receptors respond to orexin signaling, Orexin 1 Receptor
(OX1R) and Orexin 2 Receptor (OX2R) with partially overlapping brain
distributions. Genetic and pharmacological studies suggest orexin
receptor antagonists could provide therapeutic benefit for insomnia
and other disorders in which sleep/wake cycles are disrupted. Preclinical
data has also emerged showing that the orexin system is involved
in the behavioral and neurological effects of drugs of abuse ([Aston-Jones
et al., 2009] and [Harris et al., 2005]). Here we report sleep promoting
effects of a recently described small molecule dual orexin receptor
OX1R and OX2R antagonist. This dual orexin receptor antagonist (DORA)
also inhibits the ability of subchronic amphetamine to produce behavioral
sensitization measured 10 days following pre-treatment. Transcriptional
profiling of isolated reward and arousal circuits from brains of
behaviorally sensitized animals showed that the DORA blocked the
significant alteration of gene expression levels in response to amphetamine
exposure, particularly those associated with synaptic plasticity
in the VTA. Further, DORA attenuates the ability of nicotine to induce
reinstatement of extinguished responding for a reinforcer, demonstrating
selectivity of the effect to reward pathways and not to food intake.
In summary, these data demonstrate efficacy of a dual orexin receptor
antagonist for promotion of sleep and suggest that pharmacological
inhibition of the orexin system may play a role in both prevention
of drug-induced plasticity and drug-relapse.},
booktitle = {Neuropeptides},
issn = {0028-3908},
keywords = {Orexin, Sleep, Plasticity, Gene expression, Stimulant},
url = {http://www.sciencedirect.com/science/article/B6T0C-4WRD3SB-1/2/e7c5a2b2123c784a0fb31b154fe90b41}
}
@ARTICLE{Winrow2009,
author = {Winrow, Christopher J. and Tanis, Keith Q. and Rigby, Alison M. and
Taylor, Rhonda R. and Serikawa, Kyle and McWhorter, Mollie and Tokiwa,
George Y. and Marton, Matthew J. and Stone, David J. and Koblan,
Kenneth S. and Renger, John J.},
title = {Refined anatomical isolation of functional sleep circuits exhibits
distinctive regional and circadian gene transcriptional profiles},
journal = {Brain Research},
year = {2009},
volume = {1271},
pages = {1--17},
month = may,
abstract = {Powerful new approaches to study molecular variation in distinct neuronal
populations have recently been developed enabling a more precise
investigation of the control of neural circuits involved in complex
behaviors such as wake and sleep. We applied laser capture microdissection
(LCM) to isolate precise brain nuclei from rat CNS at opposing circadian
time points associated with wake and sleep. Discrete anatomical and
temporal analysis was performed to examine the extent of variation
in the transcriptional control associated with both identifiable
anatomical nuclei and with light/dark cycle. Precise isolation of
specific brain nuclei regulating sleep and arousal, including the
LC, SCN, TMN, VTA, and VLPO, demonstrated robust changes in gene
expression. Many of these differences were not observed in previous
studies where whole brain lysates or gross dissections were used
to probe for changes in gene expression. The robust and differential
profiles of genomic data obtained from the approaches used herein
underscore the requirement for careful anatomical refinement in CNS
gene expression studies designed to understand genomic control within
behaviorally-linked, but functionally isolated brain nuclei.},
issn = {0006-8993},
keywords = {Circadian, Sleep, Gene expression, Rodent, Brain},
url = {http://www.sciencedirect.com/science/article/B6SYR-4VVR1Y3-1/2/5ade0fa7bdad041c5b8f08f0630c0b4e}
}
@ARTICLE{Winter2012,
author = {Winter, Alan and Weir, William and Hunt, Martin and Berriman, Matthew
and Gilleard, John and Devaney, Eileen and Britton, Collette},
title = {Diversity in parasitic nematode genomes: the microRNAs of Brugia
pahangi and Haemonchus contortus are largely novel},
journal = {BMC Genomics},
year = {2012},
volume = {13},
pages = {4},
number = {1},
abstract = {BACKGROUND:MicroRNAs (miRNAs) play key roles in regulating post-transcriptional
gene expression and are essential for development in the free-living
nematode Caenorhabditis elegans and in higher organisms. Whether
microRNAs are involved in regulating developmental programs of parasitic
nematodes is currently unknown. Here we describe the the miRNA repertoire
of two important parasitic nematodes as an essential first step in
addressing this question.RESULTS:The small RNAs from larval and adult
stages of two parasitic species, Brugia pahangi and Haemonchus contortus,
were identified using deep-sequencing and bioinformatic approaches.
Comparative analysis to known miRNA sequences reveals that the majority
of these miRNAs are novel. Some novel miRNAs are abundantly expressed
and display developmental regulation, suggesting important functional
roles. Despite the lack of conservation in the miRNA repertoire,
genomic positioning of certain miRNAs within or close to specific
coding genes is remarkably conserved across diverse species, indicating
selection for these associations. Endogenous small-interfering RNAs
and Piwi-interacting (pi)RNAs, which regulate gene and transposon
expression, were also identified. piRNAs are expressed in adult stage
H. contortus, supporting a conserved role in germline maintenance
in some parasitic nematodes.CONCLUSIONS:This in-depth comparative
analysis of nematode miRNAs reveals the high level of divergence
across species and identifies novel sequences potentially involved
in development. Expression of novel miRNAs may reflect adaptations
to different environments and lifestyles. Our findings provide a
detailed foundation for further study of the evolution and function
of miRNAs within nematodes and for identifying potential targets
for intervention.},
url = {http://www.biomedcentral.com/1471-2164/13/4}
}
@ARTICLE{Winter2007,
author = {Winter, Stuart C. and Buffa, Francesca M. and Silva, Priyamal and
Miller, Crispin and Valentine, Helen R. and Turley, Helen and Shah,
Ketan A. and Cox, Graham J. and Corbridge, Rogan J. and Homer, Jarrod
J. and Musgrove, Brian and Slevin, Nick and Sloan, Philip and Price,
Pat and West, Catharine M.L. and Harris, Adrian L.},
title = {Relation of a Hypoxia Metagene Derived from Head and Neck Cancer
to Prognosis of Multiple Cancers},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {3441--3449},
number = {7},
month = apr,
abstract = {Affymetrix U133plus2 GeneChips were used to profile 59 head and neck
squamous cell cancers. A hypoxia metagene was obtained by analysis
of genes whose in vivo expression clustered with the expression of
10 well-known hypoxia-regulated genes (e.g., CA9, GLUT1, and VEGF).
To minimize random aggregation, strongly correlated up-regulated
genes appearing in >50% of clusters defined a signature comprising
99 genes, of which 27% were previously known to be hypoxia associated.
The median RNA expression of the 99 genes in the signature was an
independent prognostic factor for recurrence-free survival in a publicly
available head and neck cancer data set, outdoing the original intrinsic
classifier. In a published breast cancer series, the hypoxia signature
was a significant prognostic factor for overall survival independent
of clinicopathologic risk factors and a trained profile. The work
highlights the validity and potential of using data from analysis
of in vitro stress pathways for deriving a biological metagene/gene
signature in vivo. [Cancer Res 2007;67(7):3441-9]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/7/3441}
}
@ARTICLE{Winter2005,
author = {Winter, Stuart C. and Shah, Ketan A. and Campo, Leticia and Turley,
Helen and Leek, Russell and Corbridge, Rogan J. and Cox, Graham J.
and Harris, Adrian L.},
title = {Relation of Erythropoietin and Erythropoietin Receptor Expression
to Hypoxia and Anemia in Head and Neck Squamous Cell Carcinoma},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {7614--7620},
number = {21},
month = nov,
abstract = {Purpose: The use of erythropoietin in head and neck squamous cell
carcinoma (HNSCC) has been associated with poor survival. This study
examines the protein and mRNA expression of erythropoietin and erythropoietin
receptor in HNSCC and their relation to hypoxia, hemoglobin (Hb),
and clinical outcome. Experimental Design: The immunohistochemical
expression of erythropoietin and erythropoietin receptor was assessed
in 151 cases of HNSCC. Expression was compared with the hypoxia-dependent
proteins hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic
anhydrase-9 (CA-9) and correlated with clinical outcome. The mRNA
expression of erythropoietin and erythropoietin receptor was measured
in paired samples of HNSCC. Results: Erythropoietin and erythropoietin
receptor were expressed in 95% and 99% of tumors, respectively. Using
a weighed expression score, there was a positive correlation between
erythropoietin and erythropoietin receptor expression (r = 0.18,
P = 0.03). HIF-1{alpha} (r = 0.38, P < 0.01) and CA-9 (r = 0.26,
P = 0.002) correlated with erythropoietin expression, but there was
no correlation with erythropoietin receptor. No correlation was found
between Hb and erythropoietin (r = 0.07, P = 0.36) or erythropoietin
receptor (r = -0.02, P = 0.8), and no survival difference between
high and low erythropoietin or erythropoietin receptor expression
(P = 0.59 and P = 0.98, respectively). The mRNA expression of erythropoietin
(P = 0.03) but not erythropoietin receptor (P = 0.62) was significantly
increased in 11 paired samples of HNSCC. Conclusion: In vivo, the
HIF pathway regulates erythropoietin at the mRNA level but not erythropoietin
receptor expression in HNSCC. Anemia does not seem to influence the
hypoxic microenvironment of tumors sufficiently to alter the expression
of erythropoietin. The effects of exogenous erythropoietin may be
acting via receptors expressed on tumor cells in vivo, or on vascular
cells, which also express the pathway.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/21/7614}
}
@ARTICLE{Winter2011,
author = {Winter, Theresa and Winter, Jörn and Polak, Martin and Kusch, Kathrin
and Mäder, Ulrike and Sietmann, Rabea and Ehlbeck, Jörg and van
Hijum, Sacha and Weltmann, Klaus-Dieter and Hecker, Michael and Kusch,
Harald},
title = {Characterization of the global impact of low temperature gas plasma
on vegetative microorganisms},
journal = {PROTEOMICS},
year = {2011},
volume = {11},
pages = {3518--3530},
number = {17},
abstract = {Plasma medicine and also decontamination of bacteria with physical
plasmas is a promising new field of life science with huge interest
especially for medical applications. Despite numerous successful
applications of low temperature gas plasmas in medicine and decontamination,
the fundamental nature of the interactions between plasma and microorganisms
is to a large extent unknown. A detailed knowledge of these interactions
is essential for the development of new as well as for the enhancement
of established plasma-treatment procedures. In the present work we
introduce for the first time a growth chamber system suitable for
low temperature gas plasma treatment of bacteria in liquid medium.
We have coupled the use of this apparatus to a combined proteomic
and transcriptomic analyses to investigate the specific stress response
of Bacillus subtilis 168 cells to treatment with argon plasma. The
treatment with three different discharge voltages revealed not only
effects on growth, but also clear evidence of cellular stress responses.
B. subtilis suffered severe cell wall stress, which was made visible
also by electron microscopy, DNA damages and oxidative stress as
a result of exposure to plasma. These biological findings were supported
by the detection of reactive plasma species by OES measurements.},
doi = {10.1002/pmic.201000637},
issn = {1615-9861},
keywords = {Bacillus subtilis, Dielectric barrier discharge, Microbiology, Plasma–microorganism
interaction, Transcriptomics},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/pmic.201000637}
}
@ARTICLE{Winzen2007,
author = {Winzen, Reinhard and Thakur, Basant Kumar and Dittrich-Breiholz,
Oliver and Shah, Meera and Redich, Natalie and Dhamija, Sonam and
Kracht, Michael and Holtmann, Helmut},
title = {Functional Analysis of KSRP Interaction with the AU-Rich Element
of Interleukin-8 and Identification of Inflammatory mRNA Targets},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {8388--8400},
number = {23},
month = dec,
abstract = {mRNA stability is a major determinant of inflammatory gene expression.
Rapid degradation of interleukin-8 (IL-8) mRNA is imposed by a bipartite
AU-rich element (ARE) in the 3' untranslated region (R. Winzen et
al., Mol. Cell. Biol. 24:4835-4847, 2004). Small interfering RNA-mediated
knockdown of the ARE-binding protein KSRP resulted in stabilization
of IL-8 mRNA or of a {beta}-globin reporter mRNA containing the IL-8
ARE. Rapid deadenylation was impaired, indicating a crucial role
for KSRP in this step of mRNA degradation. The two IL-8 ARE domains
both contribute to interaction with KSRP, corresponding to the importance
of both domains for rapid degradation. Exposure to the inflammatory
cytokine IL-1 has been shown to stabilize IL-8 mRNA through p38 mitogen-activated
protein (MAP) kinase and MK2. IL-1 treatment impaired the interaction
of KSRP with the IL-8 ARE in a manner dependent on p38 MAP kinase
but apparently independent of MK2. Instead, evidence that TTP, a
target of MK2, can also destabilize the IL-8 ARE reporter mRNA is
presented. In a comprehensive approach to identify mRNAs controlled
by KSRP, two criteria were evaluated by microarray analysis of (i)
association of mRNAs with KSRP in pulldown assays and (ii) increased
amounts in KSRP knockdown cells. According to both criteria, a group
of 100 mRNAs is controlled by KSRP, many of which are unstable and
encode proteins involved in inflammation. These results indicate
that KSRP functions as a limiting factor in inflammatory gene expression.},
url = {http://mcb.asm.org/cgi/content/abstract/27/23/8388}
}
@ARTICLE{Wipfler2011,
author = {Wipfler, Dirk and Srinivasan, G. Vinayaga and Sadick, Haneen and
Kniep, Bernhard and Arming, Sigrid and Willhauck-Fleckenstein, Martina
and Vlasak, Reinhard and Schauer, Roland and Schwartz-Albiez, Reinhard},
title = {Differentially regulated expression of 9-O-acetyl GD3 (CD60b) and
7-O-acetyl-GD3 (CD60c) during differentiation and maturation of human
T and B lymphocytes},
journal = {Glycobiology},
year = {2011},
volume = {21},
pages = {1161-1172},
number = {9},
abstract = {GD3 (CD60a) and its 9-O-acetylated variant (CD60b) are intracellular
regulators of apoptosis in T lymphocytes. Surface expressed 9-O-acetyl-
and 7-O-acetyl-GD3 (CD60b and CD60c) may have a functional impact
on activated T and B cells. In order to investigate the balance between
surface and intracellular expression and synthesis and degradation
of these glycosphingolipids in human lymphocytes of various differentiation
stages, we analyzed (i) expression of GD3 molecules on native T and
B cells and thymocytes by flow cytometry and (ii) activity and regulation
of possible key enzymes for CD60a,b,c synthesis and degradation at
the transcriptional level. Both, surface and cytoplasmic expression
of CD60a and CD60c was highest in tonsillar T cells. In thymocytes,
CD60c outweighs the other CD60 variants and was mainly found in the
cytoplasm. All lymphocyte preparations contained sialate O-acetyltransferase
activity producing 7-O-acetyl-GD3. Sialidase activity was highest
in peripheral blood lymphocytes followed by thymocytes and tonsillar
T and B cells. Transcription of GD3 synthase (ST8SiaI), the key enzyme
for GD3 synthesis, was highest in tonsillar T cells, whereas transcriptional
levels of sialidase NEU3 and O-acetylesterase H-Lse were lowest in
activated T cells. This balance between enzymes of sialic acid metabolism
may explain the strong overall staining intensity for all GD3 forms
in T cells. Both CASD1, presumably encoding a sialic acid-specific
O-acetyltransferase, and H-Lse showed highest transcription in peripheral
B lymphocytes corresponding to the low expression of CD60b and c
in these cells. Our data point to regulatory functions of these anabolic
and catabolic key enzymes for the expression of GD3 and its O-acetylated
variants in lymphocytes at a given differentiation stage.},
doi = {10.1093/glycob/cwr050},
eprint = {http://glycob.oxfordjournals.org/cgi/reprint/21/9/1161.pdf},
url = {http://glycob.oxfordjournals.org/cgi/content/abstract/21/9/1161}
}
@ARTICLE{Wirrig2007,
author = {Wirrig, Elaine E. and Snarr, Brian S. and Chintalapudi, Mastan R.
and O'Neal, Jessica L. and Phelps, Aimee L. and Barth, Jeremy L.
and Fresco, Victor M. and Kern, Christine B. and Mjaatvedt, Corey
H. and Toole, Bryan P. and Hoffman, Stanley and Trusk, Thomas C.
and Argraves, W. Scott and Wessels, Andy},
title = {Cartilage link protein 1 (Crtl1), an extracellular matrix component
playing an important role in heart development},
journal = {Developmental Biology},
year = {2007},
volume = {310},
pages = {291--303},
number = {2},
month = oct,
abstract = {To expand our insight into cardiac development, a comparative DNA
microarray analysis was performed using tissues from the atrioventricular
junction (AVJ) and ventricular chambers of mouse hearts at embryonic
day (ED) 10.5-11.0. This comparison revealed differential expression
of approximately 200 genes, including cartilage link protein 1 (Crtl1).
Crtl1 stabilizes the interaction between hyaluronan (HA) and versican,
two extracellular matrix components essential for cardiac development.
Immunohistochemical studies showed that, initially, Crtl1, versican,
and HA are co-expressed in the endocardial lining of the heart, and
in the endocardially derived mesenchyme of the AVJ and outflow tract
(OFT). At later stages, this co-expression becomes restricted to
discrete populations of endocardially derived mesenchyme. Histological
analysis of the Crtl1-deficient mouse revealed a spectrum of cardiac
malformations, including AV septal and myocardial defects, while
expression studies showed a significant reduction in versican levels.
Subsequent analysis of the hdf mouse, which carries an insertional
mutation in the versican gene (CSPG2), demonstrated that haploinsufficient
versican mice display septal defects resembling those seen in Crtl1-/-
embryos, suggesting that reduced versican expression may contribute
to a subset of the cardiac abnormalities observed in the Crtl1-/-
mouse. Combined, these findings establish an important role for Crtl1
in heart development.},
issn = {0012-1606},
keywords = {Cartilage link protein 1, Versican, Hyaluronan, Atrioventricular cushions,
Atrioventricular septal defects, Ventricular septal defects, Thin
myocardium},
url = {http://www.sciencedirect.com/science/article/B6WDG-4PCPFND-6/2/48fd2e852c10b7c4ed681b9401c0e4ce}
}
@ARTICLE{Wirth2010,
author = {Wirth, Thomas C. and Xue, Hai-Hui and Rai, Deepa and Sabel, Jaime
T. and Bair, Tom and Harty, John T. and Badovinac, Vladimir P.},
title = {Repetitive Antigen Stimulation Induces Stepwise Transcriptome Diversification
but Preserves a Core Signature of Memory CD8+ T Cell Differentiation},
journal = {Immunity},
year = {2010},
volume = {33},
pages = {128--140},
number = {1},
month = jul,
abstract = {Summary Repetitive antigen stimulation by prime-boost vaccination
or pathogen reencounter increases memory CD8+ T cell numbers, but
the impact on memory CD8+ T cell differentiation is unknown. Here
we showed that repetitive antigen stimulations induced accumulation
of memory CD8+ T cells with uniform effector memory characteristics.
However, genome-wide microarray analyses revealed that each additional
antigen challenge resulted in the differential regulation of several
hundred new genes in the ensuing memory CD8+ T cell populations and,
therefore, in stepwise diversification of CD8+ T cell transcriptomes.
Thus, primary and repeatedly stimulated (secondary, tertiary, and
quaternary) memory CD8+ T cells differed substantially in their molecular
signature while sharing expression of a small group of genes and
biological pathways, which may constitute a core signature of memory
differentiation. These results reveal the complex regulation of memory
CD8+ T cell differentiation and identify potential new molecular
targets to dissect the function of memory cells generated by repeated
antigen stimulation.},
issn = {1074-7613},
keywords = {SYSBIO, CELLIMMUNO, MOLIMMUNO},
url = {http://www.sciencedirect.com/science/article/B6WSP-50GM4YN-1/2/36cbbf5a8ff00c030ffee5528c2af3f7}
}
@ARTICLE{Wishart2005,
author = {Wishart, Jill A. and Hayes, Andrew and Wardleworth, Leanne and Zhang,
Nianshu and Oliver, Stephen G.},
title = {Doxycycline, the drug used to control the tet-regulatable promoter
system, has no effect on global gene expression in Saccharomyces
cerevisiae},
journal = {Yeast},
year = {2005},
volume = {22},
pages = {565--569},
number = {7},
abstract = {Abstract 10.1002/yea.1225.abs The tet-regulatable promoter system
is commonly used for genetic studies in many eukaryotic organisms.
The promoter is regulated using doxycycline. There are no obvious
phenotypic effects observed when doxycycline is added to the growth
medium of yeast to control expression from the promoter. It is widely
accepted that doxycycline is innocuous to yeast. Global genetic studies
are now commonplace and the tetO-system is being used in transcriptome
studies. Hence, we wanted to ensure that the absence of phenotypic
effects, on addition of doxycycline to the growth medium, is mirrored
in transcriptome data. We have demonstrated that doxycycline has
no significant effect on global transcription levels and will continue
to use the tetO-regulatable promoter system for genetic studies.
Copyright © 2005 John Wiley & Sons, Ltd.},
issn = {1097-0061},
keywords = {Saccharomyces cerevisiae, tetracycline-regulatable promoter, doxycycline,
essential genes, global gene expression, Affymetrix arrays},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/yea.1225}
}
@ARTICLE{Wisler2011,
author = {Wisler, John A. and Afshari, Cynthia and Fielden, Mark and Zimmermann,
Cameron and Taylor, Scott and Carnahan, Josette and Vonderfecht,
Steven},
title = {Raf Inhibition Causes Extensive Multiple Tissue Hyperplasia and Urinary
Bladder Neoplasia in the Rat},
journal = {Toxicol Pathol},
year = {2011},
volume = {39},
pages = {809-822},
number = {5},
abstract = {Seven novel and potent Raf small molecule kinase inhibitors (C1-7)
were evaluated in seven-day oral repeat dose rat toxicity studies.
All compounds tested induced hyperplasia in multiple tissues. Consistently
affected was stratified squamous epithelium at a number of sites
and transitional epithelium of urinary bladder and kidney. A seven-day
time course study in rats showed morphologic evidence of epithelial
proliferation in the nonglandular stomach within four to five hours
after a single dose of C-1. Similar indications of cellular proliferation
were observed in the urinary bladder by day 2 and in the heart, kidney,
and liver by day 3. Transcriptional evidence of proliferation in
the urinary bladder was detected within four to five hours after
a single dose consistent with activation of the PI3K/AKT and ERK/MAPK
pathways. In a twenty-eight-day rat toxicity study of C-1, hyperplasia
was observed in the esophagus, nonglandular stomach, skin, urinary
bladder, kidney, and heart. Hyperplasia of transitional epithelium
of the urinary bladder was particularly severe and in one female
rat was accompanied by the presence of a transitional cell carcinoma.
These results suggest that these Raf inhibitors induce early transcriptional
changes driving unchecked cell proliferation, resulting in marked
tissue hyperplasia that can progress to carcinoma within a short
time frame.},
doi = {10.1177/0192623311410442},
eprint = {http://tpx.sagepub.com/cgi/reprint/39/5/809.pdf},
url = {http://tpx.sagepub.com/cgi/content/abstract/39/5/809}
}
@ARTICLE{Wisselink2010,
author = {Wisselink, H. Wouter and Cipollina, Chiara and Oud, Bart and Crimi,
Barbara and Heijnen, Joseph J. and Pronk, Jack T. and van Maris,
Antonius J.A.},
title = {Metabolome, transcriptome and metabolic flux analysis of arabinose
fermentation by engineered Saccharomyces cerevisiae},
journal = {Metabolic Engineering},
year = {2010},
volume = {12},
pages = {537--551},
number = {6},
month = nov,
abstract = {One of the challenges in strain improvement by evolutionary engineering
is to subsequently determine the molecular basis of the improved
properties that were enriched from the natural genetic variation
during the selective conditions. This study focuses on Saccharomyces
cerevisiae IMS0002 which, after metabolic and evolutionary engineering,
ferments the pentose sugar arabinose. Glucose- and arabinose-limited
anaerobic chemostat cultures of IMS0002 and its non-evolved ancestor
were subjected to transcriptome analysis, intracellular metabolite
measurements and metabolic flux analysis. Increased expression of
the GAL-regulon and deletion of GAL2 in IMS0002 confirmed that the
galactose transporter is essential for growth on arabinose. Elevated
intracellular concentrations of pentose-phosphate-pathway intermediates
and upregulation of TKL2 and YGR043c (encoding transketolase and
transaldolase isoenzymes) suggested an involvement of these genes
in flux-controlling reactions in arabinose fermentation. Indeed,
deletion of these genes in IMS0002 caused a 21% reduction of the
maximum specific growth rate on arabinose.},
issn = {1096-7176},
keywords = {Saccharomyces cerevisiae, Evolutionary engineering, Arabinose, Transcriptomics,
Metabolomics, Metabolic flux analysis},
url = {http://www.sciencedirect.com/science/article/B6WN3-50XCY7R-1/2/08bc66afa012ee3b13c293f0b8d237ea}
}
@ARTICLE{Wit2008,
author = {de Wit, Nicole and Bosch-Vermeulen, Hanneke and de Groot, Philip
and Hooiveld, Guido and Bromhaar, Mechteld and Jansen, Jenny and
Müller, Michael and van der Meer, Roelof},
title = {The role of the small intestine in the development of dietary fat-induced
obesity and insulin resistance in C57BL/6J mice},
journal = {BMC Medical Genomics},
year = {2008},
volume = {1},
pages = {14},
number = {1},
abstract = {BACKGROUND:Obesity and insulin resistance are two major risk factors
underlying the metabolic syndrome. The development of these metabolic
disorders is frequently studied, but mainly in liver, skeletal muscle,
and adipose tissue. To gain more insight in the role of the small
intestine in development of obesity and insulin resistance, dietary
fat-induced differential gene expression was determined along the
longitudinal axis of small intestines of C57BL/6J mice.METHODS:Male
C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked
the fatty acid composition of a Western-style human diet. After 2,
4 and 8 weeks of diet intervention small intestines were isolated
and divided in three equal parts. Differential gene expression was
determined in mucosal scrapings using Mouse genome 430 2.0 arrays.RESULTS:The
high-fat diet significantly increased body weight and decreased oral
glucose tolerance, indicating insulin resistance. Microarray analysis
showed that dietary fat had the most pronounced effect on differential
gene expression in the middle part of the small intestine. By overrepresentation
analysis we found that the most modulated biological processes on
a high-fat diet were related to lipid metabolism, cell cycle and
inflammation. Our results further indicated that the nuclear receptors
Ppars, Lxrs and Fxr play an important regulatory role in the response
of the small intestine to the high-fat diet. Next to these more local
dietary fat effects, a secretome analysis revealed differential gene
expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3
and Angptl4. Finally, we linked the fat-induced molecular changes
in the small intestine to development of obesity and insulin resistance.CONCLUSION:During
dietary fat-induced development of obesity and insulin resistance,
we found substantial changes in gene expression in the small intestine,
indicating modulations of biological processes, especially related
to lipid metabolism. Moreover, we found differential expression of
potential signaling molecules that can provoke systemic effects in
peripheral organs by influencing their metabolic homeostasis. Many
of these fat-modulated genes could be linked to obesity and/or insulin
resistance. Together, our data provided various leads for a causal
role of the small intestine in the etiology of obesity and/or insulin
resistance.},
doi = {10.1186/1755-8794-1-14},
issn = {1755-8794},
pubmedid = {18457598},
url = {http://www.biomedcentral.com/1755-8794/1/14}
}
@ARTICLE{Wit2012,
author = {Nicole J.W. de Wit and Noortje IJssennagger and Els Oosterink and
Shohreh Keshtkar and Guido J.E.J. Hooiveld and Ronald P. Mensink
and Sebastiaan Hammer and Johannes W.A. Smit and Michael Müller
and Roelof van der Meer},
title = {Oit1/Fam3D, a gut-secreted protein displaying nutritional status-dependent
regulation},
journal = {The Journal of Nutritional Biochemistry},
year = {2012},
pages = { - },
number = {0},
abstract = {Oncoprotein-induced transcript 1 (Oit1) was previously identified
as a dietary fat-induced gene in the small intestine of C57Bl/6J
mice. In this study, we further characterized Oit1 and its human
ortholog family with sequence similarity 3, member D (Fam3D), on
the messenger RNA as well as the protein level. Oit1 and Fam3D were
found to be predominantly expressed in the gastrointestinal tract
of mice and humans, respectively. Dietary fat induced a clear and
acute up-regulation of Oit1, especially in the jejunum, whereas fasting
led to a reduced gene expression in the small intestine. Regarding
protein expression, we found a remarkable pattern of Oit1 along the
longitudinal axis of the intestine, a predominant villus-restricted
expression in the proximal small intestine and a more pronounced
crypt expression in the distal parts of the intestine. Using transfection
experiments, we confirmed secretion of the Oit1 protein, as was predicted
by a signal peptide sequence. Detection of Oit1 and Fam3D in plasma
samples indicated that both proteins are secreted to the basolateral
site of enterocytes. Moreover, in human plasma samples, we also found
an effect of nutritional status on Fam3D levels, with a postprandial
elevation and a reduction after fasting. In conclusion, Oit1 and
Fam3D are gut-derived proteins that are expressed and secreted in
a nutritional status-dependent manner.},
doi = {10.1016/j.jnutbio.2011.09.003},
issn = {0955-2863},
keywords = {Oit1},
url = {http://www.sciencedirect.com/science/article/pii/S0955286311002634}
}
@ARTICLE{Witasp2011a,
author = {Witasp, Anna and Carrero, Juan J. and Hammarqvist, Folke and Qureshi,
Abdul R. and Heimbürger, Olof and Schalling, Martin and Lindholm,
Bengt and Nordfors, Louise and Stenvinkel, Peter},
title = {Expression of osteoprotegerin in human fat tissue; implications for
chronic kidney disease},
journal = {European Journal of Clinical Investigation},
year = {2011},
volume = {41},
pages = {498--506},
number = {5},
abstract = {Eur J Clin Invest 2011; 41 (5): 498–506AbstractBackground  Premature
vascular calcification (or rather ossification) significantly contributes
to morbidity and mortality in patients with chronic kidney disease
stage 5 (CKD-5) and is linked to dysregulation of bone remodelling
proteins. Recent evidence of a cross-talk between bone and fat tissue
urged us to investigate whether the calcification/ossification-associated
factors osteoprotegerin (OPG) and alpha-2-HS-glycoprotein (AHSG)
are expressed in human uremic subcutaneous adipose tissue (SAT) and
if the expression differs from nonuremic SAT.Materials and methods 
Abdominal SAT biopsies were obtained from 38 patients with CKD-5
[16 women, 58 (22–73) years old] during the surgical insertion
of a peritoneal dialysis catheter and 20 controls [11 females, 56
(40–77) years old] undergoing elective hernia repair or laparoscopic
cholecystectomy. Real-time polymerase chain reaction (PCR) quantifications
were performed followed by immunohistochemical staining and serum
protein concentration measurements. Relative mRNA expression and
protein concentrations were evaluated together with clinical parameters.
An additional 59 patients with CKD-5 were included for replication
of statistical analyses.Results OPG but not AHSG mRNAs were detected
in SAT, which were also positively immunolabelled for OPG. OPG mRNA
levels were reduced (P = 0·0001) and serum OPG concentrations
were elevated (P < 0·0001), both about twofold, in patients compared
to controls. Circulating OPG increased in proportion to BMI.Conclusions 
Human SAT expresses OPG but not AHSG, and OPG expression is reduced
in patients with CKD-5 when compared to controls, despite increased
circulating protein levels.},
doi = {10.1111/j.1365-2362.2010.02432.x},
issn = {1365-2362},
keywords = {End-stage renal disease, osteoprotegerin, uremic fat},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2362.2010.02432.x}
}
@ARTICLE{Witasp2011,
author = {Witasp, A. and Carrero, J. J. and Heimbürger, O. and Lindholm, B.
and Hammarqvist, F. and Stenvinkel, P. and Nordfors, L.},
title = {Increased expression of pro-inflammatory genes in abdominal subcutaneous
fat in advanced chronic kidney disease patients},
journal = {Journal of Internal Medicine},
year = {2011},
volume = {269},
pages = {410--419},
number = {4},
abstract = {Abstract.  Witasp A, Carrero JJ, Heimbürger O, Lindholm B, Hammarqvist
F, Stenvinkel P, Nordfors L (Karolinska Institutet, Stockholm, Sweden).
Increased expression of pro-inflammatory genes in abdominal subcutaneous
fat in advanced chronic kidney disease patients. J Intern Med 2011;
269: 410–419.Objectives.  Low-grade systemic inflammation, oxidative
stress and peripheral insulin resistance are intimately associated
and contribute to the increased risk of cardiovascular complications
in advanced chronic kidney disease (CKD). Because altered adipose
tissue activities have previously been linked to pathophysiological
processes in various inflammatory and metabolic diseases we hypothesized
that the uraemic milieu in patients with CKD may interact with the
adipose tissue, provoking an unfavourable shift in its transcriptional
output.Design.  Twenty-one adipokine mRNAs were quantified in abdominal
subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations
of inflammatory markers and related protein products were measured.Setting. 
The study was conducted at the Karolinska University Hospital, Huddinge,
and Karolinska Institutet, Stockholm, Sweden.Subjects.  Thirty-seven
patients with CKD [15 women, median 58 (interquartile range 49–65)
years] and nine nonuraemic individuals [four women, age 62 (45–64)
years] were recruited prior to initiation of peritoneal dialysis
catheter insertion or elective hernia repair/laparoscopic cholecystectomy,
respectively.Results.  Even after correction for body mass index,
SAT from patients showed a significant upregulation of inflammatory
pathway genes interleukin 6 (3.0-fold, PÂ =Â 0.0002) and suppressor
of cytokine signalling 3 (2.5-fold, PÂ =Â 0.01), as well as downregulation
of leptin (2.0-fold, PÂ =Â 0.03) and the oxidative stress genes uncoupling
protein 2 (1.5-fold, PÂ =Â 0.03) and cytochrome b-245, alpha polypeptide
(1.5-fold, P = 0.005), in relation to controls.Conclusions. 
These gene expression differences suggest that inflammatory and oxidative
stress activities may be important features of the intrinsic properties
of uraemic adipose tissue, which may have significant effects on
the uraemic phenotype.},
doi = {10.1111/j.1365-2796.2010.02293.x},
issn = {1365-2796},
keywords = {adipose tissue, end-stage renal disease},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2796.2010.02293.x}
}
@ARTICLE{Witasp2010,
author = {Witasp, Anna and Nordfors, Louise and Schalling, Martin and Nygren,
Jonas and Ljungqvist, Olle and Thorell, Anders},
title = {Expression of Inflammatory and Insulin Signaling Genes in Adipose
Tissue in Response to Elective Surgery},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {3460--3469},
number = {7},
month = jul,
abstract = {Context: The mechanisms behind postoperative insulin resistance and
impaired glucose utilization are not fully understood. Objective:
In this study, we aimed to specifically evaluate the transcription
profile of genes in the insulin and adipokine signaling pathways
in sc and omental adipose tissue after surgical injury. Design: Relative
expression of 21 target genes was analyzed in both sc and omental
adipose tissue sampled at the beginning and at the end of operation.
Setting: The study was conducted at a university-affiliated hospital.
Patients: Twelve nondiabetic patients [seven females; age, 65 (range,
46-72) yr; body mass index, 24.8 (16.5-29.8) kg/m2] undergoing major
abdominal surgery were included. Main Outcome Measurements: The changes
in mRNA levels were analyzed. Results: After surgery, both sc and
omental adipose tissue mRNA levels of genes involved in the IL6 and
nicotinamide phosphoribosyltransferase pathways were increased, whereas
mRNA levels of insulin receptor substrate 1 and adiponectin were
reduced (P < 0.05). TNF pathway genes were differently regulated
between sc and omental adipose tissue, and glucose transporter 4
mRNA levels were decreased only in omental adipose tissue. Conclusions:
The transcriptional output of pivotal inflammatory and insulin signaling
pathway genes is altered after surgery, and this pattern differs
between different fat depots. This could be of importance for the
metabolic aberrations associated to postsurgical complications, such
as insulin resistance and hyperglycemia.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/7/3460}
}
@ARTICLE{Witasp2009,
author = {Witasp, Anna and Nordfors, Louise and Schalling, Martin and Nygren,
Jonas and Ljungqvist, Olle and Thorell, Anders},
title = {Increased expression of inflammatory pathway genes in skeletal muscle
during surgery},
journal = {Clinical Nutrition},
year = {2009},
volume = {28},
pages = {291--298},
number = {3},
month = jun,
abstract = {SummaryBackground & aims Postoperative insulin resistance, resulting
in hyperglycemia, is strongly associated to morbidity and mortality
in surgical patients but the underlying mechanisms are unclear. As
increasing data suggests a link between inflammation and insulin
resistance, we aimed to evaluate if the expression of inflammatory
and insulin signaling genes is regulated in skeletal muscle during
surgery.Methods Eight patients (4 females, 63 [46-69] years, body
mass index 25.5 [16.5-29.8] kg/m2) undergoing major abdominal surgery
were included. Biopsies from m. rectus abdominis were obtained at
the beginning and at the end of the operation. mRNA levels of 45
genes were analyzed.Results The time elapsed between the two biopsies
was 224 (198-310) min. An increased (p < 0.05) expression was noted
for genes encoding both inflammatory mediators, such as interleukin
6, tumor necrosis factor, and nuclear factor of kappa light polypeptide
gene enhancer in B cells, and metabolic regulators, such as peroxisome
proliferator-activated receptor delta, while the analysis did not
detect significant expression changes of the insulin signaling pathway
genes.Conclusions The observed gene expression changes in skeletal
muscle during surgery occurred mainly in inflammatory pathways, suggesting
a possible role for inflammation in the development of postoperative
insulin resistance.},
issn = {0261-5614},
keywords = {mRNA, Surgery, Inflammation, Skeletal muscle, Insulin resistance},
url = {http://www.sciencedirect.com/science/article/B6WCM-4W0R39H-1/2/0326c4e09b849703476361235343f7de}
}
@ARTICLE{Witherspoon2010,
author = {Witherspoon, David and Xing, Jinchuan and Zhang, Yuhua and Watkins,
W Scott and Batzer, Mark and Jorde, Lynn},
title = {Mobile element scanning (ME-Scan) by targeted high-throughput sequencing},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {410},
number = {1},
abstract = {BACKGROUND:Mobile elements (MEs) are diverse, common and dynamic inhabitants
of nearly all genomes. ME transposition generates a steady stream
of polymorphic genetic markers, deleterious and adaptive mutations,
and substrates for further genomic rearrangements. Research on the
impacts, population dynamics, and evolution of MEs is constrained
by the difficulty of ascertaining rare polymorphic ME insertions
that occur against a large background of pre-existing fixed elements
and then genotyping them in many individuals.RESULTS:Here we present
a novel method for identifying nearly all insertions of a ME subfamily
in the whole genomes of multiple individuals and simultaneously genotyping
(for presence or absence) those insertions that are variable in the
population. We use ME-specific primers to construct DNA libraries
that contain the junctions of all ME insertions of the subfamily,
with their flanking genomic sequences, from many individuals. Individual-specific
"index" sequences are designed into the oligonucleotide adapters
used to construct the individual libraries. These libraries are then
pooled and sequenced using a ME-specific sequencing primer. Mobile
element insertion loci of the target subfamily are uniquely identified
by their junction sequence, and all insertion junctions are linked
to their individual libraries by the corresponding index sequence.
To test this method's feasibility, we apply it to the human AluYb8
and AluYb9 subfamilies. In four individuals, we identified a total
of 2,758 AluYb8 and AluYb9 insertions, including nearly all those
that are present in the reference genome, as well as 487 that are
not. Index counts show the sequenced products from each sample reflect
the intended proportions to within 1%. At a sequencing depth of 355,000
paired reads per sample, the sensitivity and specificity of ME-Scan
are both approximately 95%.CONCLUSIONS:Mobile Element Scanning (ME-Scan)
is an efficient method for quickly genotyping mobile element insertions
with very high sensitivity and specificity. In light of recent improvements
to high-throughput sequencing technology, it should be possible to
employ ME-Scan to genotype insertions of almost any mobile element
family in many individuals from any species.},
doi = {10.1186/1471-2164-11-410},
issn = {1471-2164},
pubmedid = {20591181},
url = {http://www.biomedcentral.com/1471-2164/11/410}
}
@ARTICLE{Witkiewicz2011,
author = {Agnieszka K. Witkiewicz and Dayana B. Rivadeneira and Adam Ertel
and Jessica Kline and Terry Hyslop and Gordon F. Schwartz and Paolo
Fortina and Erik S. Knudsen},
title = {Association of RB/p16-Pathway Perturbations with DCIS Recurrence:
Dependence on Tumor versus Tissue Microenvironment},
journal = {The American Journal of Pathology},
year = {2011},
volume = {179},
pages = {1171 - 1178},
number = {3},
abstract = {The prevalence of ductal carcinoma in situ (DCIS) diagnoses has significantly
increased as a result of active radiographic screening. Surgical
resection and hormone and radiation therapies are effective treatments,
but not all DCIS will progress to invasive breast cancer. Therefore,
markers are needed to define tumors at low risk of recurrence and
progression that can be treated by surgery alone rather than by adjuvant
therapies. Initial analyses indicate that retinoblastoma (RB)-pathway
perturbations occur at high frequency in DCIS and mirror the molecular
alterations observed in invasive breast cancer. Particularly, the
elevated expression of p16ink4a in DCIS was associated with loss
of RB function and estrogen receptor–negative biology. Furthermore,
high expression of p16ink4a in conjunction with Ki-67 was associated
with increased risk of DCIS recurrence and progression to invasive
disease in multivariate analyses. These data are consistent with
a functional role for RB in modulating the invasive behavior of mammary
epithelial cells. The tissue microenvironment is particularly relevant
to the behavior of DCIS, and, surprisingly, elevated expression of
p16ink4a in nonproliferative stroma was observed in a substantial
fraction of cases. In this tissue compartment, p16ink4a expression
was strongly associated with disease recurrence, independent of standard
histopathologic features. Together, the data herein describe dual
aspects of RB-pathway biology that are associated with disease recurrence
through the epithelial or stromal compartment of DCIS.},
doi = {10.1016/j.ajpath.2011.05.043},
issn = {0002-9440},
url = {http://www.sciencedirect.com/science/article/pii/S0002944011005426}
}
@ARTICLE{Wittig2005,
author = {Wittig, Rainer and Salowsky, Rüdiger and Blaich, Stephanie and Lyer,
Stefan and S. Maa, Juehn and Müller, Odilo and Mollenhauer, Jan
and Poustka, Annemarie},
title = {Multiplex reverse transcription-polymerase chain reaction combined
with on-chip electrophoresis as a rapid screening tool for candidate
gene sets},
journal = {ELECTROPHORESIS},
year = {2005},
volume = {26},
pages = {1687--1691},
number = {9},
abstract = {Abstract Combining multiplex reverse transcription-polymerase chain
reaction (mRT-PCR) with microfluidic amplicon analysis, we developed
an assay for the rapid and reliable semiquantitative expression screening
of 11 candidate genes for drug resistance in human malignant melanoma.
The functionality of this approach was demonstrated by low interexperimental
variations of amplicon quantities after endpoint analysis. When applied
to RNA samples derived from drug-sensitive and -resistant melanoma
cell lines, mRT-PCR delivered results qualitatively concordant with
data obtained from Northern blot and array analyses. The screening
of additional melanoma cell lines resulted in distinct expression
patterns for ten candidate genes. Our approach reveals a rapid and
easy-to-handle alternative for candidate gene set evaluation from
limited amounts of RNA.},
issn = {1522-2683},
keywords = {Bioanalyzer, Capillary electrophoresis, Drug resistance, Gene expression
screening, Miniaturization, Multiplex reverse transcription-polymerase
chain reaction},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200410237}
}
@ARTICLE{Wittmann2008,
author = {Wittmann, Jürgen and Jäck, Hans-Martin},
title = {Chapter 13 Identifying Substrates of mRNA Decay Factors by a Combined
RNA Interference and DNA Microarray Approach},
journal = {Methods Enzymol},
year = {2008},
volume = {Volume 449},
pages = {263--294},
abstract = {The complex control of gene expression has many layers, and the modulation
of posttranscriptional events receives more and more attention as
a focus of research. In this respect, regulation of mRNA turnover
is important, as the differential longevity of an mRNA enables a
cell to rapidly alter the abundance of a protein in response to intra-
and extracellular signals. While the list of factors known to catalyze
or regulate mRNA decay is steadily increasing, the substrate specificities
of most of these factors, as well as their precise roles in the degradation
of individual mRNAs, have remained elusive. One approach for determining
the substrate repertoire of a particular mRNA decay factor involves
a genome-wide DNA microarray analysis of mRNAs that accumulate in
cells in which the abundance of the respective factor has been reduced
by RNA interference. Using the knockdown of the nonsense-mediated
mRNA decay factor human UPF2 as a model system, this chapter provides
a detailed protocol of how to reduce the abundance of an mRNA decay
factor by small interfering RNAs and to determine differential mRNA
profiles by a subsequent DNA microarray analysis. Our combined RNA
interference/DNA microarray approach, as well as all experimental
protocols, can, however, be easily adapted to any mRNA decay factor
of interest.},
booktitle = {RNA Turnover in Eukaryotes: Analysis of Specialized and Quality Control
RNA Decay Pathways},
editor = {Maquat, Lynne E. and Kiledjian, Megerditch},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B7CV2-4VK64G8-M/2/18c975cccdd58add3baa6fc75f1a41ab}
}
@ARTICLE{Wittwer2010,
author = {Wittwer, Matthias and Grandgirard, Denis and Rohrbach, Janine and
Leib, Stephen},
title = {Tracking the transcriptional host response from the acute to the
regenerative phase of experimental pneumococcal meningitis},
journal = {BMC Infectious Diseases},
year = {2010},
volume = {10},
pages = {176},
number = {1},
abstract = {BACKGROUND:Despite the availability of effective antibiotic therapies,
pneumococcal meningitis (PM) has a case fatality rate of up to 30%
and causes neurological sequelae in up to half of the surviving patients.
The underlying brain damage includes apoptosis of neurons in the
hippocampus and necrosis in the cortex. Therapeutic options to reduce
acute injury and to improve outcome from PM are severely limited.With
the aim to develop new therapies a number of pharmacologic interventions
have been evaluated. However, the often unpredictable outcome of
interventional studies suggests that the current concept of the pathophysiologic
events during bacterial meningitis is fragmentary. The aim of this
work is to describe the transcriptomic changes underlying the complex
mechanisms of the host response to pneumococcal meningitis in a temporal
and spatial context using a well characterized infant rat model.METHODS:Eleven
days old nursing Wistar rats were infected by direct intracisternal
injection of 2 × 106cfu/ml of Streptococcus pneumoniae. Animals were
sacrificed at 1, 3, 10 and 26 days after infection, the brain harvested
and the cortex and hippocampus were sampled. The first two time points
represent the acute and sub-acute phase of bacterial meningitis,
whereas the latter represent the recovery phase of the disease.RESULTS:The
major events in the regulation of the host response on a transcriptional
level occur within the first 3 days after infection. Beyond this
time, no differences in global gene expression in infected and control
animals were detectable by microarray analysis. Whereas in the acute
phase of the disease immunoregulatory processes prevail in the hippocampus
and the cortex, we observed a strong activation of neurogenic processes
in the hippocampal dentate gyrus, both by gene expression and immunohistology
starting as early as 3 days after infection.CONCLUSIONS:Here we describe
the cellular pathways involved in the host response to experimental
pneumococcal meningitis in specified disease states and brain regions.
With these results we hope to provide the scientific basis for the
development of new treatment strategies which take the temporal aspects
of the disease into account.},
doi = {10.1186/1471-2334-10-176},
issn = {1471-2334},
pubmedid = {20565785},
url = {http://www.biomedcentral.com/1471-2334/10/176}
}
@ARTICLE{Wlodarczyk2006,
author = {Wlodarczyk, Bogdan J. and Cabrera, Robert M. and Hill, Denise S.
and Bozinov, Daniel and Zhu, Huiping and Finnell, Richard H.},
title = {Arsenic-induced gene expression changes in the neural tube of folate
transport defective mouse embryos},
journal = {NeuroToxicology},
year = {2006},
volume = {27},
pages = {547--557},
number = {4},
month = jul,
abstract = {Arsenic injected intraperitoneally (i.p.) during early organogenesis
to small pregnant laboratory rodents (mouse, rat, and hamster) induces
several congenital defects in the progeny. Among those abnormalities
consistently and predominantly observed are exencephaly and encephalocele.
These severe defects of the central nervous system originate from
a corrupted process of neurulation and are better known as neural
tube defects (NTDs). In order to understand the mechanism of arsenate-induced
NTDs, we designed studies in which highly sensitive Folr2 nullizygous
mice were injected intraperitoneally with sodium arsenate at the
beginning of the neural tube formation process. This specific knockout
mouse and the arsenic exposure conditions were chosen as they were
known to provide a high incidence of exencephaly in exposed embryos.
We have applied gene expression technology to the anterior neural
tube. This allowed us to study arsenic-induced changes in patterns
of gene expression that may contribute to the development of neural
tube defects in these mice. Using extensive data analysis approaches
including hierarchical clustering and gene ontology analysis, we
identified several candidate genes as well as important ontology
groups that may be responsible for arsenic's teratogenicity. Changes
in the expression of several genes in response to arsenic treatment
in our model had previously been demonstrated by other investigators
to also induce NTDs in murine model systems. These include: engrailed
1 (En-1), platelet derived growth factor receptor alpha (Pdgfr[alpha])
and ephrinA7 (EphA7). We also found several gene ontology groups
that could be implicated in arsenic's underlying teratogenicity:
morphogenesis, oxidative phosporylation, redox response, and regulation
of I-kappaB kinase/NF-kappaB cascade. Additionally, we revealed new
target genes which may be responsible for arsenic disrupted oxidative
phosphorylation.},
issn = {0161-813X},
keywords = {Sodium arsenate, Folr2 knockout mouse, Neural tube, Microarray},
url = {http://www.sciencedirect.com/science/article/B6W81-4JRVFP5-1/2/961f2b694f332b17f75a709e1f3cb835}
}
@ARTICLE{Wlodkowic2011,
author = {Donald Wlodkowic and Zbigniew Darzynkiewicz},
title = {Chapter 5 - Rise of the Micromachines: Microfluidics and the Future
of Cytometry},
journal = {Methods in Cell Biology},
year = {2011},
volume = {102},
pages = {105 - 125},
abstract = {The past decade has brought many innovations to the field of flow
and image-based cytometry. These advancements can be seen in the
current miniaturization trends and simplification of analytical components
found in the conventional flow cytometers. On the other hand, the
maturation of multispectral imaging cytometry in flow imaging and
the slide-based laser scanning cytometers offers great hopes for
improved data quality and throughput while proving new vistas for
the multiparameter, real-time analysis of cells and tissues. Importantly,
however, cytometry remains a viable and very dynamic field of modern
engineering. Technological milestones and innovations made over the
last couple of years are bringing the next generation of cytometers
out of centralized core facilities while making it much more affordable
and user friendly. In this context, the development of microfluidic,
lab-on-a-chip (LOC) technologies is one of the most innovative and
cost-effective approaches toward the advancement of cytometry. LOC
devices promise new functionalities that can overcome current limitations
while at the same time promise greatly reduced costs, increased sensitivity,
and ultra high throughputs. We can expect that the current pace in
the development of novel microfabricated cytometric systems will
open up groundbreaking vistas for the field of cytometry, lead to
the renaissance of cytometric techniques and most importantly greatly
support the wider availability of these enabling bioanalytical technologies.},
doi = {10.1016/B978-0-12-374912-3.00005-5},
editor = {Zbigniew Darzynkiewicz, Elena Holden, Alberto Orfao, William Telford
and Donald Wlodkowic},
issn = {0091-679X},
keywords = {Array},
publisher = {Academic Press},
series = {Methods in Cell Biology},
url = {http://www.sciencedirect.com/science/article/pii/B9780123749123000055}
}
@ARTICLE{Wlodkowic2009,
author = {Wlodkowic, Donald and Skommer, Joanna and Faley, Shannon and Darzynkiewicz,
Zbigniew and Cooper, Jonathan M.},
title = {Dynamic analysis of apoptosis using cyanine SYTO probes: From classical
to microfluidic cytometry},
journal = {Experimental Cell Research},
year = {2009},
volume = {315},
pages = {1706--1714},
number = {10},
month = jun,
abstract = {Cell death is a stochastic process, often initiated and/or executed
in a multi-pathway/multi-organelle fashion. Therefore, high-throughput
single-cell analysis platforms are required to provide detailed characterization
of kinetics and mechanisms of cell death in heterogeneous cell populations.
However, there is still a largely unmet need for inert fluorescent
probes, suitable for prolonged kinetic studies. Here, we compare
the use of innovative adaptation of unsymmetrical SYTO dyes for dynamic
real-time analysis of apoptosis in conventional as well as microfluidic
chip-based systems. We show that cyanine SYTO probes allow non-invasive
tracking of intracellular events over extended time. Easy handling
and "stain-no wash" protocols open up new opportunities for high-throughput
analysis and live-cell sorting. Furthermore, SYTO probes are easily
adaptable for detection of cell death using automated microfluidic
chip-based cytometry. Overall, the combined use of SYTO probes and
state-of-the-art Lab-on-a-Chip platform emerges as a cost effective
solution for automated drug screening compared to conventional Annexin
V or TUNEL assays. In particular, it should allow for dynamic analysis
of samples where low cell number has so far been an obstacle, e.g.
primary cancer stems cells or circulating minimal residual tumors.},
issn = {0014-4827},
keywords = {SYTO, Apoptosis, Kinetic assays, Antitumor drugs, Microfluidics, Lab-on-a-Chip,
Flow cytometry},
url = {http://www.sciencedirect.com/science/article/B6WFC-4VVR1YR-3/2/dbf9d645ce496977a0dba3e9bd47a685}
}
@ARTICLE{Woeckel2010,
author = {Woeckel, V.J. and Alves, R.D.A.M. and Swagemakers, S.M.A. and Eijken,
M. and Chiba, H. and van der Eerden, B.C.J. and van Leeuwen, J.P.T.M.},
title = {1alpha,25-(OH)2D3 acts in the early phase of osteoblast differentiation
to enhance mineralization via accelerated production of mature matrix
vesicles},
journal = {J. Cell. Physiol.},
year = {2010},
volume = {225},
pages = {593--600},
number = {2},
abstract = {Abstract 1α,25-dihydroxyitamin D3 (1,25D3) deficiency leads to impaired
bone mineralization. We used the human pre-osteoblastic cell line
SV-HFO, which forms within 19 days of culture an extracellular matrix
that starts to mineralize around day 12, to examine the mechanism
by which 1,25D3 regulates osteoblasts and directly stimulates mineralization.
Time phase studies showed that 1,25D3 treatment prior to the onset
of mineralization, rather than during mineralization led to accelerated
and enhanced mineralization. This is supported by the observation
of unaltered stimulation by 1,25D3 even when osteoblasts were devitalized
just prior to onset of mineralization and after 1,25D3 treatment.
Gene Chip expression profiling identified the pre-mineralization
and mineralization phase as two strongly distinctive transcriptional
periods with only 0.6% overlap of genes regulated by 1,25D3. In neither
phase 1,25D3 significantly altered expression of extracellular matrix
genes. 1,25D3 significantly accelerated the production of mature
matrix vesicles (MVs) in the pre-mineralization. Duration rather
than timing determined the extent of the 1,25D3 effect. We propose
the concept that besides indirect effects via intestinal calcium
uptake 1,25D3 directly accelerates osteoblast-mediated mineralization
via increased production of mature MVs in the period prior to mineralization.
The accelerated deposition of mature MVs leads to an earlier onset
and higher rate of mineralization. These effects are independent
of changes in extracellular matrix protein composition. These data
on 1,25D3, mineralization, and MV biology add new insights into the
role of 1,25D3 in bone metabolism and emphasize the importance of
MVs in bone and maintaining bone health and strength by optimal mineralization
status. J. Cell. Physiol. 225: 593–600, 2010. © 2010 Wiley-Liss,
Inc.},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22244}
}
@ARTICLE{Woelfelschneider2008,
author = {Woelfelschneider, Andreas and Popanda, Odilia and Lilla, Carmen and
Linseisen, Jakob and Mayer, Claudia and Celebi, Oktay and Debus,
Jurgen and Bartsch, Helmut and Chang-Claude, Jenny and Schmezer,
Peter},
title = {A distinct ERCC1 haplotype is associated with mRNA expression levels
in prostate cancer patients},
journal = {Carcinogenesis},
year = {2008},
volume = {29},
pages = {1758--1764},
number = {9},
month = sep,
abstract = {Both genetic variants and messenger RNA (mRNA) expression of DNA repair
and tumor suppressor genes have been investigated as molecular markers
for therapy outcome. However, the phenotypic impact of genetic variants
often remained unclear, thus the rationale of their use in risk prediction
may be limited. We therefore analyzed genetic variants together with
anthropometric and lifestyle factors to see how these affect mRNA
levels of ERCC1, MDM2 and TP53 in primary blood lymphocytes. mRNA
expression was measured in 376 prostate cancer patients by quantitative
real-time polymerase chain reaction after reverse transcription,
and ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and
TP53 rs17878362 (p53PIN3) polymorphisms were determined. Considerable
interindividual differences in mRNA expression were found (coefficients
of variation: ERCC1, 45%; MDM2, 43% and TP53, 35%). ERCC1 expression
was positively correlated with plasma levels of {beta}-carotene (P
= 0.03) and negatively correlated with canthaxanthin (P = 0.02) and
lutein (P = 0.02). Overall, the polymorphisms affected mRNA expression
only weakly. Carriers of a distinct ERCC1 haplotype (CC) showed,
however, significantly lower expression values than non-carriers
(P = 0.001). Applying logistic regression, we found that CC haplotype
carriers had a 1.69-fold increased odds ratio (95% confidence interval:
1.06-2.71) for reduced ERCC1 mRNA levels. This low ERCC1 expression
might be associated with reduced DNA repair and better therapy response.
In summary, the association we have found between ERCC1 genotype
and mRNA expression supports recent clinical observations that genetic
variation in ERCC1 can affect treatment outcome and prognosis. Our
study further revealed a modulating effect by nutritional factors.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/29/9/1758}
}
@BOOK{Woelk2011,
title = {Chapter 3 - The Utility of Gene Expression in Blood Cells for Diagnosing
Neuropsychiatric Disorders},
publisher = {Academic Press},
year = {2011},
editor = {Paul C. Guest and Sabine Bahn},
author = {Christopher H. Woelk and Akul Singhania and Josué Pérez-Santiago
and Stephen J. Glatt and Ming T. Tsuang},
volume = {101},
pages = {41 - 63},
series = {International Review of Neurobiology},
abstract = {Abstract Objective diagnostic tools are required for neuropsychiatric
disorders. Gene expression in blood cells may provide such a tool
and has already been used to construct classifiers capable of diagnosing
many human diseases. This chapter discusses the use of microarray
gene expression data to construct diagnostic classifiers for neuropsychiatric
disorders. The potential pitfalls of microarray gene expression analysis
and the experimental design and methods suitable for classifier construction
are described in detail. A review of studies that have analyzed gene
expression in blood cells from patients with neuropsychiatric disorders
is presented with an emphasis on the feasibility of generating a
diagnostic classifier for schizophrenia. Finally, the future directions
of the field are discussed with respect to using blood gene expression
to tailor antipsychotic medications to individual patients, applying
microRNA expression for diagnostic purposes, as well as the implications
of next-generation sequencing technologies for gene expression analysis.},
booktitle = {Biomarkers of Neurological and Psychiatric Disease},
doi = {10.1016/B978-0-12-387718-5.00003-1},
issn = {0074-7742},
keywords = {diagnostic classifier},
url = {http://www.sciencedirect.com/science/article/pii/B9780123877185000031}
}
@ARTICLE{Woenckhaus2006,
author = {Woenckhaus, M and Klein-Hitpass, L and Grepmeier, U and Merk, J and
Pfeifer, M and Wild, PJ and Bettstetter, M and Wuensch, P and Blaszyk,
H and Hartmann, A and Hofstaedter, F and Dietmaier, W},
title = {Smoking and cancer-related gene expression in bronchial epithelium
and non-small-cell lung cancers},
journal = {J. Pathol.},
year = {2006},
volume = {210},
pages = {192--204},
number = {2},
abstract = {Abstract 10.1002/path.2039.abs Tobacco smoking is the leading cause
of lung cancer worldwide. Gene expression in surgically resected
and microdissected samples of non-small-cell lung cancers (18 squamous
cell carcinomas and nine adenocarcinomas), matched normal bronchial
epithelium, and peripheral lung tissue from both smokers (n = 22)
and non-smokers (n = 5) was studied using the Affymetrix U133A array.
A subset of 15 differentially regulated genes was validated by real-time
PCR or immunohistochemistry. Hierarchical cluster analysis clearly
distinguished between benign and malignant tissue and between squamous
cell carcinomas and adenocarcinomas. The bronchial epithelium and
adenocarcinomas could be divided into the two subgroups of smokers
and non-smokers. By comparison of the gene expression profiles in
the bronchial epithelium of non-smokers, smokers, and matched cancer
tissues, it was possible to identify a signature of 23 differentially
expressed genes, which might reflect early cigarette smoke-induced
and cancer-relevant molecular lesions in the central bronchial epithelium
of smokers. Ten of these genes are involved in xenobiotic metabolism
and redox stress (eg AKR1B10, AKR1C1, and MT1K). One gene is a tumour
suppressor gene (HLF); two genes act as oncogenes (FGFR3 and LMO3);
two genes are involved in matrix degradation (MMP12 and PTHLH); three
genes are related to cell differentiation (SPRR1B, RTN1, and MUC7);
and five genes have not been well characterized to date. By comparison
of the tobacco-exposed peripheral alveolar lung tissue of smokers
with non-smokers and with adenocarcinomas from smokers, it was possible
to identify a signature of 27 other differentially expressed genes.
These genes are involved in the metabolism of xenobiotics (eg GPX2
and FMO3) and may represent cigarette smoke-induced, cancer-related
molecular targets that may be utilized to identify smokers with increased
risk for lung cancer. Copyright © 2006 Pathological Society of Great
Britain and Ireland. Published by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {gene expression, cDNA array, NSCLC, benign bronchial epithelium, smoker
and non-smoker},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2039}
}
@ARTICLE{Woesten2006,
author = {Woesten, Marc M. S. M. and Parker, Craig T. and Van Mourik, Andries
and Guilhabert, Magalie R. and Van Dijk, Linda and Van Putten, Jos
P. M.},
title = {The Campylobacter jejuni PhosS/PhosR operon represents a non-classical
phosphate-sensitive two-component system},
journal = {Molecular Microbiology},
year = {2006},
volume = {62},
pages = {278--291},
number = {1},
abstract = {Summary The bacterial pathogen Campylobacter jejuni carries several
putative two-component signal transduction systems of unknown function.
Here we report that the PhosS (Cj0889) and PhosR (Cj0890) proteins
constitute a two-component system that is activated by phosphate
limitation. Microarray analysis, real-time RT-PCR, and primer extension
experiments indicated that this system regulates 12 genes (including
the pstSCAB genes) present in three transcriptional units. Gel shift
assays confirmed that recombinant PhosR protein bound DNA fragments
containing the promoter regions upstream of these three transcriptional
units. Although functionally similar, the PhosS/PhosR does not exhibit
sequence homology with the classical PhoBR systems, has a different
pho box (5′-GTTTCNAAAANGTTTC-3′) recognized by the C. jejuni
response regulator, and is not autoregulated. Because of these atypical
properties, we designated the Cj0889-Cj0890 operon as the C. jejuni
PhosS/PhosR system (phosphate sensor/phosphate response regulator)
and the phosphate-regulated genes as the pho regulon of C. jejuni.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2006.05372.x}
}
@ARTICLE{Wohlbrand2008,
author = {Wohlbrand, Lars and Wilkes, Heinz and Halder, Thomas and Rabus, Ralf},
title = {Anaerobic Degradation of p-Ethylphenol by "Aromatoleum aromaticum"
Strain EbN1: Pathway, Regulation, and Involved Proteins},
journal = {J. Bacteriol.},
year = {2008},
volume = {190},
pages = {5699--5709},
number = {16},
month = aug,
abstract = {The denitrifying "Aromatoleum aromaticum" strain EbN1 was demonstrated
to utilize p-ethylphenol under anoxic conditions and was suggested
to employ a degradation pathway which is reminiscent of known anaerobic
ethylbenzene degradation in the same bacterium: initial hydroxylation
of p-ethylphenol to 1-(4-hydroxyphenyl)-ethanol followed by dehydrogenation
to p-hydroxyacetophenone. Possibly, subsequent carboxylation and
thiolytic cleavage yield p-hydroxybenzoyl-coenzyme A (CoA), which
is channeled into the central benzoyl-CoA pathway. Substrate-specific
formation of three of the four proposed intermediates was confirmed
by gas chromatographic-mass spectrometric analysis and also by applying
deuterated p-ethylphenol. Proteins suggested to be involved in this
degradation pathway are encoded in a single large operon-like structure
([~]15 kb). Among them are a p-cresol methylhydroxylase-like protein
(PchCF), two predicted alcohol dehydrogenases (ChnA and EbA309),
a biotin-dependent carboxylase (XccABC), and a thiolase (TioL). Proteomic
analysis (two-dimensional difference gel electrophoresis) revealed
their specific and coordinated upregulation in cells adapted to anaerobic
growth with p-ethylphenol and p-hydroxyacetophenone (e.g., PchF up
to 29-fold). Coregulated proteins of currently unknown function (e.g.,
EbA329) are possibly involved in p-ethylphenol- and p-hydroxyacetophenone-specific
solvent stress responses and related to other aromatic solvent-induced
proteins of strain EbN1.},
url = {http://jb.asm.org/cgi/content/abstract/190/16/5699}
}
@ARTICLE{Wojcik2006,
author = {Wojcik, Cezary and Rowicka, Maga and Kudlicki, Andrzej and Nowis,
Dominika and McConnell, Elizabeth and Kujawa, Marek and DeMartino,
George N.},
title = {Valosin-containing Protein (p97) Is a Regulator of Endoplasmic Reticulum
Stress and of the Degradation of N-End Rule and Ubiquitin-Fusion
Degradation Pathway Substrates in Mammalian Cells},
journal = {Mol. Biol. Cell},
year = {2006},
volume = {17},
pages = {4606--4618},
number = {11},
month = nov,
abstract = {Valosin-containing protein (VCP; p97; cdc48 in yeast) is a hexameric
ATPase of the AAA family (ATPases with multiple cellular activities)
involved in multiple cellular functions, including degradation of
proteins by the ubiquitin (Ub)-proteasome system (UPS). We examined
the consequences of the reduction of VCP levels after RNA interference
(RNAi) of VCP. A new stringent method of microarray analysis demonstrated
that only four transcripts were nonspecifically affected by RNAi,
whereas [~]30 transcripts were affected in response to reduced VCP
levels in a sequence-independent manner. These transcripts encoded
proteins involved in endoplasmic reticulum (ER) stress, apoptosis,
and amino acid starvation. RNAi of VCP promoted the unfolded protein
response, without eliciting a cytosolic stress response. RNAi of
VCP inhibited the degradation of R-GFP (green fluorescent protein)
and Ub-G76V-GFP, two cytoplasmic reporter proteins degraded by the
UPS, and of {alpha} chain of the T-cell receptor, an established
substrate of the ER-associated degradation (ERAD) pathway. Surprisingly,
RNAi of VCP had no detectable effect on the degradation of two other
ERAD substrates, {alpha}1-antitrypsin and {delta}CD3. These results
indicate that VCP is required for maintenance of normal ER structure
and function and mediates the degradation of some proteins via the
UPS, but is dispensable for the UPS-dependent degradation of some
ERAD substrates.},
url = {http://www.molbiolcell.org/cgi/content/abstract/17/11/4606}
}
@ARTICLE{Wojnarowicz2008,
author = {Wojnarowicz, P.m. And Breznan, A. And Arcand, S.l. And Filali-mouhim,
A. And Provencher, D.m. And Mes-masson, A.-m. And Tonin, P.n.},
title = {Construction of a chromosome 17 transcriptome in serous ovarian cancer
identifies differentially expressed genes},
journal = {International Journal of Gynecological Cancer},
year = {2008},
volume = {18},
pages = {963--975},
number = {5},
abstract = {Abstract Cytogenetic, molecular genetic, and functional analyses have
implicated chromosome 17 genes in epithelial ovarian cancer (EOC).
To further characterize the contribution of chromosome 17 genes in
EOC, the Affymetrix U133A GeneChip was used to perform transcriptome
analyses of 15 primary cultures of normal ovarian surface epithelial
(NOSE) cells and 17 malignant ovarian tumor (TOV) samples of the
serous histopathologic subtype. A two-way comparative analysis of
776 known genes and expressed sequences identified 253 genes that
exhibited at least a threefold difference in expression in at least
one TOV sample compared to the mean of NOSE samples. Within this
data set, 99 of the 253 (39.1%) genes exhibited similar patterns
of expression across all tested samples, suggesting a high degree
of concordance in the chromosome 17 transcriptome. This observation
was supported by hierarchical clustering analysis that segregated
the TOV and NOSE samples into two separate groups. There were 77
genes that were differentially expressed in at least 50% of the TOV
samples. Five genes (AdoRA2Bat 17p12, CCL2 at 17q12, ACLY at 17q21.2,
WIPI1 at 17q24.2, and SLC16A3 at 17q25.3) were significantly (P <
5.13E−11) differentially expressed at least threefold in all serous
TOV samples, and all five genes were underexpressed in these TOV
samples as compared to the NOSE samples. Interestingly, several of
these differentially expressed genes have been previously associated
with response to hypoxia.},
issn = {1525-1438},
keywords = {chromosome 17, expression microarray, hypoxia, ovarian cancer, transcriptome},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1111/j.1525-1438.2007.01134.x}
}
@ARTICLE{Wolber2006,
author = {Wolber, Paul K. and Collins, Patrick J. and Lucas, Anne B. and De
Witte, Anniek and Shannon, Karen W.},
title = {The Agilent In Situ[hyphen (true graphic)]Synthesized Microarray
Platform},
journal = {Methods Enzymol},
year = {2006},
volume = {Volume 410},
pages = {28--57},
abstract = {Microarray technology has become a standard tool in many laboratories.
Agilent Technologies manufactures a variety of catalog and custom
long[hyphen (true graphic)]oligonucleotide (60[hyphen (true graphic)]mer)
microarrays that can be used in multiple two[hyphen (true graphic)]color
microarray applications. Optimized methods and techniques have been
developed for two such applications: gene expression profiling and
comparative genomic hybridization. Methods for a third technique,
location analysis, are evolving rapidly. This chapter outlines current
best methods for using Agilent microarrays, provides detailed instructions
for the most recently developed techniques, and discusses solutions
to common problems encountered with two[hyphen (true graphic)]color
microarrays.},
booktitle = {DNA Microarrays, Part A: Array Platforms and Wet-Bench Protocols},
editor = {Alan Kimmel and Oliver, Brian},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B7CV2-4KS57R8-2/2/0a06edeb24277302523cb1dc38bf85a2}
}
@ARTICLE{Wolf2010,
author = {Wolf, Diana and Kalamorz, Falk and Wecke, Tina and Juszczak, Anna
and Mader, Ulrike and Homuth, Georg and Jordan, Sina and Kirstein,
Janine and Hoppert, Michael and Voigt, Birgit and Hecker, Michael
and Mascher, Thorsten},
title = {In-Depth Profiling of the LiaR Response of Bacillus subtilis},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {4680--4693},
number = {18},
month = sep,
abstract = {The Lia system, a cell envelope stress response module of Bacillus
subtilis, is comprised of the LiaRS two-component system and a membrane-anchored
inhibitor protein, LiaF. It is highly conserved in the Firmicutes
bacteria, and all orthologs investigated so far are activated by
cell wall antibiotics. In response to envelope stress, the systems
in Firmicutes cocci induce the expression of a number of genes that
are involved in conferring resistance against its inducers. In contrast,
a complete picture of the LiaR regulon of B. subtilis is still missing
and no phenotypes could be associated with mutants lacking LiaRS.
Here, we performed genome-wide transcriptomic, proteomic, and in-depth
phenotypic profiling of constitutive "Lia ON" and "Lia OFF" mutants
to obtain a comprehensive picture of the Lia response of Bacillus
subtilis. In addition to the known targets liaIH and yhcYZ-yhdA,
we identified ydhE as a novel gene affected by LiaR-dependent regulation.
The results of detailed follow-up gene expression studies, together
with proteomic analysis, demonstrate that the liaIH operon represents
the only relevant LiaR target locus in vivo. It encodes a small membrane
protein (LiaI) and a phage shock protein homolog (LiaH). LiaH forms
large oligomeric rings reminiscent of those described for Escherichia
coli PspA or Arabidopsis thaliana Vipp1. The results of comprehensive
phenotype studies demonstrated that the gene products of the liaIH
operon are involved in protecting the cell against oxidative stress
and some cell wall antibiotics. Our data suggest that the LiaFSR
system of B. subtilis and, presumably, other Firmicutes bacilli coordinates
a phage shock protein-like response.},
url = {http://jb.asm.org/cgi/content/abstract/192/18/4680}
}
@ARTICLE{WOLF2010,
author = {WOLF, JOCHEN B. W. and BAYER, TILL and HAUBOLD, BERNHARD and SCHILHABEL,
MARKUS and ROSENSTIEL, PHILIP and TAUTZ, DIETHARD},
title = {Nucleotide divergence vs. gene expression differentiation: comparative
transcriptome sequencing in natural isolates from the carrion crow
and its hybrid zone with the hooded crow},
journal = {Molecular Ecology},
year = {2010},
volume = {19},
pages = {162--175},
abstract = {Abstract Recent advances in sequencing technology promise to provide
new strategies for studying population differentiation and speciation
phenomena in their earliest phases. We focus here on the black carrion
crow (Corvus [corone] corone), which forms a zone of hybridization
and overlap with the grey coated hooded crow (Corvus [corone] cornix).
However, although these semispecies are taxonomically distinct, previous
analyses based on several types of genetic markers did not reveal
significant molecular differentiation between them. We here corroborate
this result with sequence data obtained from a set of 25 nuclear
intronic loci. Thus, the system represents a case of a very early
phase of species divergence that requires new molecular approaches
for its description. We have therefore generated RNAseq expression
profiles using barcoded massively parallel pyrosequencing of brain
mRNA from six individuals of the carrion crow and five individuals
from a hybrid zone with the hooded crow. We obtained 856Â 675 reads
from two runs, with average read length of 270 nt and coverage of
8.44. Reads were assembled de novo into 19Â 552 contigs, 70% of which
could be assigned to annotated genes in chicken and zebra finch.
This resulted in a total of 7637 orthologous genes and a core set
of 1301 genes that could be compared across all individuals. We find
a clear clustering of expression profiles for the pure carrion crow
animals and disperse profiles for the animals from the hybrid zone.
These results suggest that gene expression differences may indeed
be a sensitive indicator of initial species divergence.},
issn = {1365-294X},
keywords = {Dobzhansky–Muller incompatibilities, EST, gene expression, postzygotic
isolation, RNAseq, speciation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-294X.2009.04471.x}
}
@ARTICLE{Wolff2007,
author = {Wolff, George L. and Stanley, J. Steven and Ferguson, Matthew E.
and Simpson, Pippa M. and Ronis, Martin J. J. and Badger, Thomas
M.},
title = {A BRIEF COMMUNICATION: Agouti Signaling Protein Stimulates Cell Division
in "Viable Yellow" (Avy/a) Mouse Liver},
journal = {Exp Biol Med},
year = {2007},
volume = {232},
pages = {1326--1329},
number = {10},
month = nov,
abstract = {Enhanced linear growth, hyperplasia, and tumorigenesis are well-known
characteristics of "viable yellow" agouti Avy/- mice (Wolff GL, Roberts
DW, Mountjoy KG. Physiol Genomics 1:151-163, 1999); however, the
functional basis for this aspect of the phenotype is unknown. In
the present study, we ascertained whether agouti signaling protein
(ASIP) levels in Avy/a or a/a livers are associated with hepatocyte
proliferation as a possible factor in promotion of hepatocellular
tumor formation. Proliferating cell nuclear antigen (PCNA) assays
and quantitative real-time reverse transcriptase polymerase chain
reaction assays were performed on liver samples from mottled yellow
Avy/a, pseudoagouti Avy/a, and black a/a VY mice to determine mitotic
indices and expression levels of Avy and a in relation to the expression
level of the housekeeping gene hprt. We found that ASIP levels were
~100-fold higher in yellow than in pseudoagouti or black mice and
that the proportion of PCNA-positive hepatocytes was greater (P <
0.001) in yellow than in pseudoagouti or black mice.},
url = {http://ebm.rsmjournals.com/cgi/content/abstract/232/10/1326}
}
@ARTICLE{Wolff2010,
author = {Wolff, J-C. and Wilhelm, J. and Fink, L. and Seeger, W. and Voswinckel,
R.},
title = {Comparative gene expression profiling of post-natal and post-pneumonectomy
lung growth},
journal = {Eur. Respir. J.},
year = {2010},
volume = {35},
pages = {655--666},
number = {3},
month = mar,
abstract = {Although increasing numbers of patients suffer from chronic destructive
lung diseases, there are no effective therapeutic options apart from
transplantation. Understanding the mechanisms of physiological and
regenerative alveolar septation is prerequisite for the development
of regenerative therapies for the lung. We compared lung gene expression
in the phase of induction of post-natal and post-pneumonectomy alveolarisation
to identify regulatory genes involved in both processes. We performed
genome-wide microarray screenings of newborn and pneumonectomised
mouse lungs 1 and 3 days after birth or surgery. Selected candidates
were validated by real-time PCR, Western blot and in situ hybridisation.
We found 58 genes to be regulated in both models with 40 candidates
being changed likewise. Many of these genes participated in growth
and differentiation processes. Additionally, immune system, structural
molecules, respiratory chain, signal transduction and metabolism
were involved. Some candidates were not yet linked to specific functions.
The highest regulatory concordance was observed for various isoforms
of (pro-)collagen molecules, elastin and the elastin-associated protein
fibrillin1 being corporately upregulated. Our findings do not definitively
support a common regulating mechanism for induction of post-natal
and adult alveolarisation, but some candidates in the intersection
of both models are promising for further investigations.},
url = {http://erj.ersjournals.com/cgi/content/abstract/35/3/655}
}
@ARTICLE{Wolfs2010a,
author = {Wolfs, Marcel and Rensen, Sander and Bruin-Van Dijk, Elinda and Verdam,
Froukje and Greve, Jan-Willem and Sanjabi, Bahram and Bruinenberg,
Marcel and Wijmenga, Cisca and van Haeften, Timon and Buurman, Wim
and Franke, Lude and Hofker, Marten},
title = {Co-expressed immune and metabolic genes in visceral and subcutaneous
adipose tissue from severely obese individuals are associated with
plasma HDL and glucose levels: a microarray study},
journal = {BMC Medical Genomics},
year = {2010},
volume = {3},
pages = {34},
number = {1},
abstract = {BACKGROUND:Excessive accumulation of body fat, in particular in the
visceral fat depot, is a major risk factor to develop a variety of
diseases such as type 2 diabetes. The mechanisms underlying the increased
risk of obese individuals to develop co-morbid diseases are largely
unclear.We aimed to identify genes expressed in subcutaneous adipose
tissue (SAT) and visceral adipose tissue (VAT) that are related to
blood parameters involved in obesity co-morbidity, such as plasma
lipid and glucose levels, and to compare gene expression between
the fat depots.METHODS:Whole-transcriptome SAT and VAT gene expression
levels were determined in 75 individuals with a BMI >35 kg/m2. Modules
of co-expressed genes likely to be functionally related were identified
and correlated with BMI, plasma levels of glucose, insulin, HbA1c,
triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive
protein, and LDL- and HDL cholesterol.RESULTS:Of the approximately
70 modules identified in SAT and VAT, three SAT modules were inversely
associated with plasma HDL-cholesterol levels, and a fourth module
was inversely associated with both plasma glucose and plasma triglyceride
levels (p < 5.33 × 10-5). These modules were markedly enriched in
immune and metabolic genes. In VAT, one module was associated with
both BMI and insulin, and another with plasma glucose (p < 4.64 ×
10-5). This module was also enriched in inflammatory genes and showed
a marked overlap in gene content with the SAT modules related to
HDL. Several genes differentially expressed in SAT and VAT were identified.CONCLUSIONS:In
obese subjects, groups of co-expressed genes were identified that
correlated with lipid and glucose metabolism parameters; they were
enriched with immune genes. A number of genes were identified of
which the expression in SAT correlated with plasma HDL cholesterol,
while their expression in VAT correlated with plasma glucose. This
underlines both the singular importance of these genes for lipid
and glucose metabolism and the specific roles of these two fat depots
in this respect.},
doi = {10.1186/1755-8794-3-34},
issn = {1755-8794},
pubmedid = {20687939},
url = {http://www.biomedcentral.com/1755-8794/3/34}
}
@ARTICLE{Wolfs2010,
author = {Wolfs, Tim G.A.M. and Derikx, Joep P.M. and Hodin, Caroline M.I.M.
and Vanderlocht, Joris and Driessen, Ann and de Bruïne, Adriaan
P. and Bevins, Charles L. and Lasitschka, Felix and Gassler, Nikolaus
and van Gemert, Wim G. and Buurman, Wim A.},
title = {Localization of the lipopolysaccharide recognition complex in the
human healthy and inflamed premature and adult gut},
journal = {Inflamm Bowel Dis},
year = {2010},
volume = {16},
pages = {68--75},
number = {1},
abstract = {Abstract 10.1002/ibd.20995.abs Background: Microbiota in the intestinal
lumen provide an abundant source of potentially detrimental antigens,
including lipopolysaccharide (LPS), a potent immunostimulatory product
of Gram-negative bacteria recognized by the host via TLR-4 and MD-2.
An aberrant immune response to LPS or other bacterial antigens has
been linked to inflammatory bowel disease (IBD) and necrotizing enterocolitis
(NEC). Methods: We investigated which cells express MD-2 in the normal
and inflamed ileum from neonates and adults by immunohistochemistry.
Moreover, MD-2 and TLR4 mRNA expression in normal adult ileum was
studied by reverse-transcription polymerase chain reaction (RT-PCR)
on cells isolated by laser capture microdissection. Results: Premature
infants did not show MD-2 expression either in epithelial cells or
in the lamina propria. Similarly, MD-2 was absent in epithelial cells
and lamina propria inflammatory cells in preterm infants with NEC.
MD-2 protein in the healthy term neonatal and adult ileum was predominantly
expressed by Paneth cells and some resident inflammatory cells in
the lamina propria. MD-2 and TLR-4 mRNA expression was restricted
to crypt cells. Also in IBD, Paneth cells were still the sole MD-2-expressing
epithelial cells, whereas inflammatory cells (mainly plasma cells)
were responsible for the vast majority of the MD-2 expression. Conclusions:
The absence of MD-2 in the immature neonatal gut suggests impaired
LPS sensing, which could predispose neonates to NEC upon microbial
colonization of the immature intestine. The apparent expression of
MD-2 by Paneth cells supports the critical concept that these cells
respond to luminal bacterial products in order to maintain homeostasis
with the intestinal microbiota in vivo. (Inflamm Bowel Dis 2010;)},
issn = {1536-4844},
keywords = {inflammatory bowel disease, necrotizing enterocolitis, TLR4, MD-2,
immunohistochemistry, laser capture microdissection},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.20995}
}
@ARTICLE{Wolins2006,
author = {Wolins, Nathan E. and Quaynor, Benjamin K. and Skinner, James R.
and Tzekov, Anatoly and Croce, Michelle A. and Gropler, Matthew C.
and Varma, Vijayalakshmi and Yao-Borengasser, Aiwei and Rasouli,
Neda and Kern, Philip A. and Finck, Brian N. and Bickel, Perry E.},
title = {OXPAT/PAT-1 Is a PPAR-Induced Lipid Droplet Protein That Promotes
Fatty Acid Utilization},
journal = {Diabetes},
year = {2006},
volume = {55},
pages = {3418--3428},
number = {12},
month = dec,
abstract = {Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47)
family regulate cellular neutral lipid stores. We have studied a
new member of this family, PAT-1, and found that it is expressed
in highly oxidative tissues. We refer to this protein as "OXPAT."
Physiologic lipid loading of mouse liver by fasting enriches OXPAT
in the lipid droplet tissue fraction. OXPAT resides on lipid droplets
with the PAT protein adipophilin in primary cardiomyocytes. Ectopic
expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation,
long-chain fatty acid oxidation, and mRNAs associated with oxidative
metabolism. Consistent with these observations, OXPAT is induced
in mouse adipose tissue, striated muscle, and liver by physiological
(fasting), pathophysiological (insulin deficiency), pharmacological
(peroxisome proliferator-activated receptor [PPAR] agonists), and
genetic (muscle-specific PPAR{alpha} overexpression) perturbations
that increase fatty acid utilization. In humans with impaired glucose
tolerance, PPAR{gamma} agonist treatment induces adipose OXPAT mRNA.
Further, adipose OXPAT mRNA negatively correlates with BMI in nondiabetic
humans. Our collective data in cells, mice, and humans suggest that
OXPAT is a marker for PPAR activation and fatty acid oxidation. OXPAT
likely contributes to adaptive responses to the fatty acid burden
that accompanies fasting, insulin deficiency, and overnutrition,
responses that are defective in obesity and type 2 diabetes.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/55/12/3418}
}
@ARTICLE{Wollenick2011,
author = {Wollenick, Kristin and Hu, Jun and Kristiansen, Glen and Schraml,
Peter and Rehrauer, Hubert and Berchner-Pfannschmidt, Utta and Fandrey,
Joachim and Wenger, Roland H. and Stiehl, Daniel P.},
title = {Synthetic transactivation screening reveals ETV4 as broad coactivator
of hypoxia-inducible factor signaling},
journal = {Nucleic Acids Res.},
year = {2011},
pages = {gkr978},
abstract = {The human prolyl-4-hydroxylase domain (PHD) proteins 1-3 are known
as cellular oxygen sensors, acting via the degradation of hypoxia-inducible
factor (HIF) -subunits. PHD2 and PHD3 genes are inducible by HIFs
themselves, suggesting a negative feedback loop that involves PHD
abundance. To identify novel regulators of the PHD2 gene, an expression
array of 704 transcription factors was screened by a method that
allows distinguishing between HIF-dependent and HIF-independent promoter
regulation. Among others, the E-twenty six transcription factor ETS
translocation variant 4 (ETV4) was found to contribute to PHD2 gene
expression particularly under hypoxic conditions. Mechanistically,
complex formation between ETV4 and HIF-1/2 was observed by mammalian
two-hybrid and fluorescence resonance energy transfer analysis. HIF-1
domain mapping, CITED2 overexpression and factor inhibiting HIF depletion
experiments provided evidence for cooperation between HIF-1 and p300/CBP
in ETV4 binding. Chromatin immunoprecipitation confirmed ETV4 and
HIF-1 corecruitment to the PHD2 promoter. Of 608 hypoxically induced
transcripts found by genome-wide expression profiling, 7.7% required
ETV4 for efficient hypoxic induction, suggesting a broad role of
ETV4 in hypoxic gene regulation. Endogenous ETV4 highly correlated
with PHD2, HIF-1/2 and several established markers of tissue hypoxia
in 282 human breast cancer tissue samples, corroborating a functional
interplay between the ETV4 and HIF pathways.},
doi = {10.1093/nar/gkr978},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/gkr978v1.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/gkr978v1}
}
@ARTICLE{Woltje2006,
author = {Woltje, Michael and Tschoke, Beate and von Bulow, Verena and Westenfeld,
Ralf and Denecke, Bernd and Graber, Steffen and Jahnen-Dechent, Willi},
title = {CCAAT enhancer binding protein {beta} and hepatocyte nuclear factor
3{beta} are necessary and sufficient to mediate dexamethasone-induced
up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression},
journal = {J. Mol. Endocrinol.},
year = {2006},
volume = {36},
pages = {261--277},
number = {2},
month = apr,
abstract = {Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing
soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated
and therefore considered a negative acute phase protein. Enhancement
of Ahsg expression as a protective serum protein is desirable in
several diseases including tissue remodelling after trauma and infection,
kidney and heart failure, and cancer. Using reporter gene assays
in hepatoma cells combined with electrophoretic mobility shift assays
we determined that dexamethasone up-regulates hepatic Ahsg. A steroid
response unit at position -146/-119 within the mouse Ahsg promoter
mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds
the hepatocyte nuclear factor 3{beta} and CCAAT enhancer binding
protein {beta} (C/EBP-{beta}). The up-regulation is mediated indirectly
via glucocorticoid hormone-induced transcriptional up-regulation
in C/EBP-{beta} protein. A high degree of sequence identity in mouse,
rat and human Ahsg promoters suggests that the promoter is similarly
up-regulated by dexamethasone in all three species. Therefore, our
findings suggest that glucocorticoids may be used to enhance the
level of Ahsg protein circulating in serum.},
url = {http://jme.endocrinology-journals.org/cgi/content/abstract/36/2/261}
}
@ARTICLE{Won2009,
author = {Won, Jungyeon and Gifford, Elaine and Smith, Richard S. and Yi, Haiqing
and Ferreira, Paulo A. and Hicks, Wanda L. and Li, Tiansen and Naggert,
Jurgen K. and Nishina, Patsy M.},
title = {RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration
and morphogenesis},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {4329--4339},
number = {22},
month = nov,
abstract = {The function of the retinitis pigmentosa GTPase regulator interacting
protein 1 (RPGRIP1) gene is currently not known. However, mutations
within the gene lead to Leber Congenital Amaurosis and autosomal
recessive retinitis pigmentosa in human patients. In a previously
described knockout mouse model of the long splice variant of Rpgrip1,
herein referred to as Rpgrip1tm1Tili mice, mislocalization of key
outer segment proteins and dysmorphogenesis of outer segment discs
preceded subsequent photoreceptor degeneration. In this report, we
describe a new mouse model carrying a splice acceptor site mutation
in Rpgrip1, herein referred to as Rpgrip1nmf247 that is phenotypically
distinct from Rpgrip1tm1Tili mice. Photoreceptor degeneration in
homozygous Rpgrip1nmf247 mice is earlier in onset and more severe
when compared with Rpgrip1tm1Tili mice. Also, ultrastructural studies
reveal that whereas Rpgrip1nmf247 mutants have a normal structure
and number of connecting cilia, unlike Rpgrip1tm1Tili mice, they
do not elaborate rod outer segments (OS). Therefore, in addition
to its role in OS disc morphogenesis, RPGRIP1 is essential for rod
OS formation. Our study indicates the absence of multiple Rpgrip1
isoforms in Rpgrip1nmf247 mice, suggesting different isoforms may
play different roles in photoreceptors and underscores the importance
of considering splice variants when generating targeted null mutations.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/22/4329}
}
@ARTICLE{Won2010,
author = {Won, Ji Yeong and Min, Junhong},
title = {Highly sensitive Escherichia coli O157:H7 detection in a large volume
sample using a conical polymer tube chamber consisting of micro-glass
beads},
journal = {Biosensors and Bioelectronics},
year = {2010},
volume = {26},
pages = {112--117},
number = {1},
month = sep,
abstract = {In this study, we developed a method for the highly sensitive detection
of viable pathogenic bacteria in a large volume sample by performing
RNA concentration, amplification, and using fluorescently tagged
capture probes in a single polymer chamber without transferring RNA
samples from one chamber to another. Nucleic acids were extracted
from Escherichia coli O157:H7 and loaded into glass micro-beads embedded
in a conical polymer tube chamber. Nucleic acids were concentrated
in the micro-tube in a low pH buffer (pH 5). The mRNA, which was
adsorbed to the glass micro-beads, was amplified by Nucleic Acid
Sequence Based Amplification in the same chamber at a relatively
high pH (pH 8.9). The products amplified were measured using the
hair-loop type detection probe with FAM and DABCYL, which was pre-mixed
in the NASBA mater mixture. As a result, high sensitivity (100% for
rain water and 60% for river water) with less than 10 viable E. coli
O157:H7 in 100 ml could be achieved within 4 h using the simple method
proposed in this study.},
issn = {0956-5663},
keywords = {RNA concentration, NSABA, Glass micro-bead, Molecular beacon, Escherichia
coli O157:H7},
url = {http://www.sciencedirect.com/science/article/B6TFC-5051PFT-3/2/9884ea87e8e028bd4f39b0075abf389a}
}
@ARTICLE{Wonders2008,
author = {Wonders, Carl P. and Taylor, Lauren and Welagen, Jelle and Mbata,
Ihunanya C. and Xiang, Jenny Z. and Anderson, Stewart A.},
title = {A spatial bias for the origins of interneuron subgroups within the
medial ganglionic eminence},
journal = {Developmental Biology},
year = {2008},
volume = {314},
pages = {127--136},
number = {1},
month = feb,
abstract = {Although it is well established that the ventral telencephalon is
the primary source of GABAergic cortical interneurons in rodents,
little is known about the specification of specific interneuron subtypes.
It is also unclear whether the potential to achieve a given fate
is established at their place of origin or by signals received during
their migration to or during their maturation within the cerebral
cortex. Using both in vivo and in vitro transplantation techniques,
we find that two major interneuron subgroups have largely distinct
origins within the MGE. Somatostatin (SST)-expressing interneurons
are primarily generated within the dorsal MGE, while parvalbumin
(PV)-expressing interneurons primarily originate from the ventral
MGE. In addition, we show that significant heterogeneity exists between
gene expression patterns in the dorsal and ventral MGE. These results
suggest that, like the spinal cord, neuronal fate determination in
the ventral telencephalon is largely the result of spatially segregated,
molecularly distinct microdomains arranged on the dorsal-ventral
axis.},
issn = {0012-1606},
keywords = {MGE, Somatostatin, Parvalbumin, Microarray, Interneuron subtypes},
url = {http://www.sciencedirect.com/science/article/B6WDG-4R7J89F-3/2/34f25d17deb4ec2fada21ff28331c8c4}
}
@ARTICLE{Wong2011,
author = {Wong, Chun Nin Adam and Ng, Patrick and Douglas, Angela E.},
title = {Low-diversity bacterial community in the gut of the fruitfly Drosophila
melanogaster},
journal = {Environmental Microbiology},
year = {2011},
volume = {13},
pages = {1889--1900},
number = {7},
abstract = {The bacteria in the fruitfly Drosophila melanogaster of different
life stages was quantified by 454 pyrosequencing of 16S rRNA gene
amplicons. The sequence reads were dominated by 5 operational taxonomic
units (OTUs) at ≤ 97% sequence identity that could be assigned
to Acetobacter pomorum, A. tropicalis, Lactobacillus brevis, L. fructivorans
and L. plantarum. The saturated rarefaction curves and species richness
indices indicated that the sampling (85 000–159 000 reads per
sample) was comprehensive. Parallel diagnostic PCR assays revealed
only minor variation in the complement of the five bacterial species
across individual insects and three D. melanogaster strains. Other
gut-associated bacteria included 6 OTUs with low %ID to previously
reported sequences, raising the possibility that they represent novel
taxa within the genera Acetobacter and Lactobacillus. A developmental
change in the most abundant species, from L. fructivorans in young
adults to A. pomorum in aged adults was identified; changes in gut
oxygen tension or immune system function might account for this effect.
Host immune responses and disturbance may also contribute to the
low bacterial diversity in the Drosophila gut habitat.},
doi = {10.1111/j.1462-2920.2011.02511.x},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2011.02511.x}
}
@ARTICLE{Wong2007,
author = {Wong, John and Korcheva, Veselina and Jacoby, David B. and Magun,
Bruce},
title = {Intrapulmonary Delivery of Ricin at High Dosage Triggers a Systemic
Inflammatory Response and Glomerular Damage},
journal = {Am. J. Pathol.},
year = {2007},
volume = {170},
pages = {1497--1510},
number = {5},
month = may,
abstract = {In view of the possibility that ricin may be used as a bioweapon against
human populations, we examined the pathological consequences that
occur in mice after introduction of ricin into the pulmonary system.
Intratracheal instillation of a lethal dose of ricin (20 {micro}g/100
g body weight) resulted in a hemorrhagic inflammatory response in
multiple organs, accompanied by activation of mitogen-activated protein
kinases, increased synthesis of proinflammatory RNA transcripts,
and increased levels of circulating cytokines and chemokines. A sublethal
dose of instilled ricin (2 {micro}g/100 g body weight) induced a
similar response in lungs but did not cause detectable damage in
other organs. Lungs of mice that recovered from a sublethal dose
of ricin displayed evidence of fibrosis and residual damage. A lethal
dose of ricin caused accumulation of proinflammatory RNA transcripts
and substantial damage to 28S rRNA of multiple organs, including
lung, kidney, spleen, liver, and blood, demonstrating that instilled
ricin gained access to the circulation. The kidneys of mice instilled
with a lethal dose of ricin showed accumulation of fibrin/fibrinogen
in glomerular capillaries, increased numbers of glomerular leukocytes,
and impairment of kidney function. A sublethal dose of ricin failed
to induce damage to 28S rRNA in kidney or other extrapulmonary organs.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/170/5/1497}
}
@ARTICLE{Wong2007a,
author = {Wong, John and Korcheva, Veselina and Jacoby, David B. and Magun,
Bruce E.},
title = {Proinflammatory responses of human airway cells to ricin involve
stress-activated protein kinases and NF-{kappa}B},
journal = {Am J Physiol Lung Cell Mol Physiol},
year = {2007},
volume = {293},
pages = {L1385--1394},
number = {6},
month = dec,
abstract = {Ricin is a potential bioweapon because of its toxicity, availability,
and ease of production. When delivered to the lungs, ricin causes
severe pulmonary damage with symptoms that are similar to those observed
in acute lung injury and adult respiratory distress syndrome. The
airway epithelium plays an important role in the pathogenesis of
many lung diseases, but its role in ricin intoxication has not been
elucidated. Exposure of cultured primary human airway epithelial
cells to ricin resulted in the activation of SAPKs and NF-{kappa}B
and in the increased expression of multiple proinflammatory molecules.
Among the genes upregulated by ricin and identified by microarray
analysis were those associated with transcription, nucleosome assembly,
inflammation, and response to stress. Sequence analysis of the promoters
of these genes identified NF-{kappa}B as one of the transcription
factors whose binding sites were overrepresented. Although airway
cells secrete TNF-{alpha} in response to ricin, blocking TNF-{alpha}
did not prevent ricin-induced activation of NF-{kappa}B. Decreased
levels of I{kappa}B-{alpha} in airway cells exposed to ricin suggest
that translational suppression may be responsible for the activation
of NF-{kappa}B. Inhibition of p38 MAPK by a chemical inhibitor or
NF-{kappa}B by short interfering RNA resulted in a marked reduction
in the expression of proinflammatory genes, demonstrating the importance
of these two pathways in ricin intoxication. Therefore, the p38 MAPK
and NF-{kappa}B pathways are potential therapeutic targets for reducing
the inflammatory consequences of ricin poisoning.},
url = {http://ajplung.physiology.org/cgi/content/abstract/293/6/L1385}
}
@ARTICLE{Wong2009,
author = {Wong, Kevin and Lyddon, Rebecca and Dracheva, Stella},
title = {TaqMan-based, real-time quantitative polymerase chain reaction method
for RNA editing analysis},
journal = {Analytical Biochemistry},
year = {2009},
volume = {390},
pages = {173--180},
number = {2},
month = jul,
abstract = {Abnormal adenosine to inosine (A-to-I) messenger RNA (mRNA) editing
has been linked to several disease states afflicting the central
nervous system. Here we report an assay to determine RNA editing
frequencies at specific sites that is based on quantitative polymerase
chain reaction (qPCR) with TaqMan probes. The assay was tested by
measuring the frequency of the A-to-I mRNA editing at the Q/R site
of the human kainate receptor subunit GluR5 and was compared with
two established methods of assessing RNA editing: sequencing of individual
clones and restriction analysis. The qPCR assay displayed high sensitivity
and reproducibility, demonstrated exceptional discrimination between
edited and unedited transcript variants, and proved to have several
advantages over the other editing methods. Due to the fact that TaqMan-based
qPCR technology can be easily adapted to different editing targets,
the increased capabilities afforded by this new technique should
facilitate various RNA editing studies that aim to elucidate the
role of this process in normal physiology and in disease.},
issn = {0003-2697},
keywords = {RNA editing, GluR5, Multiplex qPCR, Taqman},
url = {http://www.sciencedirect.com/science/article/B6W9V-4W2NDSR-1/2/5cfab2a132bb9a97847f1192fc27460e}
}
@ARTICLE{Wong2011a,
author = {Wong, Melissa and Cannon, Charles and Wickneswari, Ratnam},
title = {Identification of lignin genes and regulatory sequences involved
in secondary cell wall formation in Acacia auriculiformis and Acacia
mangium via de novo transcriptome sequencing},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {342},
number = {1},
abstract = {BACKGROUND:Acacia auriculiformis x Acacia mangium hybrids are commercially
important trees for the timber and pulp industry in Southeast Asia.
Increasing pulp yield while reducing pulping costs are major objectives
of tree breeding programs. The general monolignol biosynthesis and
secondary cell wall formation pathways are well-characterized but
genes in these pathways are poorly characterized in Acacia hybrids.
RNA-seq on short-read platforms is a rapid approach for obtaining
comprehensive transcriptomic data and to discover informative sequence
variants.RESULTS:We sequenced transcriptomes of A. auriculiformis
and A. mangium from non-normalized cDNA libraries synthesized from
pooled young stem and inner bark tissues using paired-end libraries
and a single lane of an Illumina GAII machine. De novo assembly produced
a total of 42,217 and 35,759 contigs with an average length of 496
bp and 498 bp for A. auriculiformis and A. mangium respectively.
The assemblies of A. auriculiformis and A. mangium had a total length
of 21,022,649 bp and 17,838,260 bp, respectively, with the largest
contig 15,262 bp long. We detected all ten monolignol biosynthetic
genes using Blastx and further analysis revealed 18 lignin isoforms
for each species. We also identified five contigs homologous to R2R3-MYB
proteins in other plant species that are involved in transcriptional
regulation of secondary cell wall formation and lignin deposition.
We searched the contigs against public microRNA database and predicted
the stem-loop structures of six highly conserved microRNA families
(miR319, miR396, miR160, miR172, miR162 and miR168) and one legume-specific
family (miR2086). Three microRNA target genes were predicted to be
involved in wood formation and flavonoid biosynthesis. By using the
assemblies as a reference, we discovered 16,648 and 9,335 high quality
putative Single Nucleotide Polymorphisms (SNPs) in the transcriptomes
of A. auriculiformis and A. mangium, respectively, thus yielding
useful markers for population genetics studies and marker-assisted
selection.CONCLUSION:We have produced the first comprehensive transcriptome-wide
analysis in A. auriculiformis and A. mangium using de novo assembly
techniques. Our high quality and comprehensive assemblies allowed
the identification of many genes in the lignin biosynthesis and secondary
cell wall formation in Acacia hybrids. Our results demonstrated that
Next Generation Sequencing is a cost-effective method for gene discovery,
identification of regulatory sequences, and informative markers in
a non-model plant.},
doi = {10.1186/1471-2164-12-342},
issn = {1471-2164},
pubmedid = {21729267},
url = {http://www.biomedcentral.com/1471-2164/12/342}
}
@ARTICLE{Wong2008,
author = {Wong, Rebecca Lee Yean and Wlodarczyk, Bogdan J. and Min, Kyung Soo
and Scott, Melissa L. and Kartiko, Susan and Yu, Wei and Merriweather,
Michelle Y. and Vogel, Peter and Zambrowicz, Brian P. and Finnell,
Richard H.},
title = {Mouse Fkbp8 activity is required to inhibit cell death and establish
dorso-ventral patterning in the posterior neural tube},
journal = {Hum. Mol. Genet.},
year = {2008},
volume = {17},
pages = {587--601},
number = {4},
month = feb,
abstract = {Neural tube defects (NTDs) are birth defects that can be disabling
or lethal and are second in their prevalence after cardiac defects
among major human congenital malformations. Spina bifida is a NTD
where the spinal cord is dysplastic, and the overlying spinal column
is absent. At present, the molecular mechanisms underlying the spinal
bifida development are largely unknown. In this study, we present
a Fkbp8 mouse mutant that has an isolated and completely penetrant
spina bifida, which is folate- and inositol-resistant. Fkbp8 mutants
are not embryo lethal, but they display striking features of human
spina bifida, including a dysplastic spinal cord, open neural canal
and disability. The loss of Fkbp8 leads to increased apoptosis in
the posterior neural tube, demonstrating that in vivo FKBP8 inhibits
cell death. Gene expression analysis of Fkbp8 mutants revealed a
perturbation of expression of neural tube patterning genes, suggesting
that endogenous FKBP8 activity establishes dorso-ventral patterning
of the neural tube. These studies demonstrate that Fkbp8 is not important
for embryo survival, but is essential for spinal neural tube patterning,
and to block apoptosis, in the developing neural tube. The mutant
Fkbp8 allele is a new experimental model which will be useful in
dissecting the pathogenesis of spinal NTDs, and enhance our understanding
of the etiology of human NTDs.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/17/4/587}
}
@ARTICLE{Wong2010,
author = {Wong, Stephen and Tan, Kheng and Carey, Kirstyn T. and Fukushima,
Atsushi and Tiganis, Tony and Cole, Timothy J.},
title = {Glucocorticoids Stimulate Hepatic and Renal Catecholamine Inactivation
by Direct Rapid Induction of the Dopamine Sulfotransferase Sult1d1},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {185--194},
number = {1},
month = jan,
abstract = {During the stress response and metabolic fasting, glucocorticoids
acting via the glucocorticoid receptor (GR) stimulate hepatic glucose
production by activating specific gluconeogenic enzyme target genes.
To characterize novel direct GR-regulated hepatic target genes under
glucocorticoid control, we performed a whole genome gene expression
microarray using dexamethasone-treated GR-null mice. Strongly induced
previously characterized genes included phosphoenolpyruvate carboxykinase,
serine dehydratase, tyrosine oxygenase, lipin 1, metallothionine,
and cdkn1A. Novel induced genes included Ddit4, Fkbp5, Megf9, Sult1e1,
and Sult1d1, and all were verified by real-time PCR. Sult1d1, a sulfotransferase,
is a member of a large superfamily of detoxification enzymes and
has an important role in the inactivation of endogenous dopamine-derived
compounds, including the catecholamines. Treatment of primary mouse
hepatocytes with dexamethasone for 6 h dramatically increased Sult1d1
mRNA levels, whereas cotreatment with RU-486, a GR antagonist, blocked
induction by dexamethasone. Sult1d1 mRNA levels were also increased
by dexamethasone in the kidney, a major site of Sult1d1 synthesis.
Sult1d1 mRNA was localized by in situ hybridization to renal collecting
ducts and was rapidly induced by glucocorticoids in renal inner medullary
collecting duct (IMCD3) cells. Hepatic and renal Sult1d1 enzymatic
activity was significantly induced in vivo in wild-type mice 6 h
after dexamethasone treatment. Chromatin immunoprecipitation assay
analysis upstream of the Sult1d1 gene promoter identified a glucocorticoid
response element close to the neighboring glucocorticoid-responsive
estrogen sulfotransferase Sult1e1 gene, indicating that both genes
potentially share a common glucocorticoid response element. These
results suggest that Sult1d1 in mice is directly induced by glucocorticoids
and may attenuate elevated catecholamine activity during the stress
response.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/1/185}
}
@ARTICLE{Wong2008a,
author = {Wong, Vietty and Wang, Dong-Yu and Warren, Keisha and Kulkarni, Supriya
and Boerner, Scott and Done, Susan and Leong, Wey},
title = {The effects of timing of fine needle aspiration biopsies on gene
expression profiles in breast cancers},
journal = {BMC Cancer},
year = {2008},
volume = {8},
pages = {277},
number = {1},
abstract = {BACKGROUND:DNA microarray analysis has great potential to become an
important clinical tool to individualize prognostication and treatment
for breast cancer patients. However, with any emerging technology,
there are many variables one must consider before bringing the technology
to the bedside. There are already concerted efforts to standardize
protocols and to improve reproducibility of DNA microarray. Our study
examines one variable that is often overlooked, the timing of tissue
acquisition, which may have a significant impact on the outcomes
of DNA microarray analyses especially in studies that compare microarray
data based on biospecimens taken in vivo and ex vivo.METHODS:From
16 patients, we obtained paired fine needle aspiration biopsies (FNABs)
of breast cancers taken before (PRE) and after (POST) their surgeries
and compared the microarray data to determine the genes that were
differentially expressed between the FNABs taken at the two time
points. qRT-PCR was used to validate our findings. To examine effects
of longer exposure to hypoxia on gene expression, we also compared
the gene expression profiles of 10 breast cancers from clinical tissue
bank.RESULTS:Using hierarchical clustering analysis, 12 genes were
found to be differentially expressed between the FNABs taken before
and after surgical removal. Remarkably, most of the genes were linked
to FOS in an early hypoxia pathway. The gene expression of FOS also
increased with longer exposure to hypoxia.CONCLUSION:Our study demonstrated
that the timing of fine needle aspiration biopsies can be a confounding
factor in microarray data analyses in breast cancer. We have shown
that FOS-related genes, which have been implicated in early hypoxia
as well as the development of breast cancers, were differentially
expressed before and after surgery. Therefore, it is important that
future studies take timing of tissue acquisition into account.},
doi = {10.1186/1471-2407-8-277},
issn = {1471-2407},
pubmedid = {18826606},
url = {http://www.biomedcentral.com/1471-2407/8/277}
}
@ARTICLE{Wonodi2009,
author = {Wonodi, Ikwunga and Hong, L. Elliot and Stine, O. Colin and Mitchell,
Braxton D. and Elliott, Amie and Roberts, Rosalinda C. and Conley,
Robert R. and McMahon, Robert P. and Thaker, Gunvant K.},
title = {Dopamine transporter polymorphism modulates oculomotor function and
DAT1 mRNA expression in schizophrenia},
journal = {Am. J. Med. Genet.},
year = {2009},
volume = {150B},
pages = {282--289},
number = {2},
abstract = {Abstract 10.1002/ajmg.b.30811.abs Smooth pursuit eye movement (SPEM)
deficit is an established schizophrenia endophenotype with a similar
neurocognitive construct to working memory. Frontal eye field (FEF)
neurons controlling SPEM maintain firing when visual sensory information
is removed, and their firing rates directly correlate with SPEM velocity.
We previously demonstrated a paradoxical association between a functional
polymorphism of dopamine signaling (COMT gene) and SPEM. Recent evidence
implicates the dopamine transporter gene (DAT1) in modulating cortical
dopamine and associated neurocognitive functions. We hypothesized
that DAT1 10/10 genotype, which reduces dopamine transporter expression
and increases extracellular dopamine, would affect SPEM. We examined
the effects of DAT1 genotype on: Clinical diagnosis in the study
sample (n = 418; 190 with schizophrenia), SPEM measures in a
subgroup with completed oculomotor measures (n = 200; 87 schizophrenia),
and DAT1 gene expression in FEF tissue obtained from postmortem brain
samples (n = 32; 16 schizophrenia). DAT1 genotype was not associated
with schizophrenia. DAT1 10/10 genotype was associated with better
SPEM in healthy controls, intermediate SPEM in unaffected first-degree
relatives of schizophrenia subjects, and worse SPEM in schizophrenia
subjects. In the gene expression study, DAT1 10/10 genotype was associated
with significantly reduced DAT1 mRNA transcript in FEF tissue from
healthy control donors (P < 0.05), but higher expression in schizophrenia
donors. Findings suggest regulatory effects of another gene(s) or
etiological factor in schizophrenia, which modulate DAT1 gene function.
© 2008 Wiley-Liss, Inc.},
issn = {1552-485X},
keywords = {DAT1 gene, expression, endophenotype, schizophrenia},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.30811}
}
@ARTICLE{Wonodi2011,
author = {Wonodi, Ikwunga and Stine, O. Colin and Sathyasaikumar, Korrapati
V. and Roberts, Rosalinda C. and Mitchell, Braxton D. and Hong, L.
Elliot and Kajii, Yasushi and Thaker, Gunvant K. and Schwarcz, Robert},
title = {Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme
Activity in Schizophrenia and Genetic Association With Schizophrenia
Endophenotypes},
journal = {Arch Gen Psychiatry},
year = {2011},
volume = {68},
pages = {665-674},
number = {7},
abstract = {Context Kynurenic acid, a metabolite of the kynurenine pathway of
tryptophan degradation, is an antagonist at N-methyl-D-aspartate
and 7 nicotinic acetylcholine receptors and modulates glutamate,
dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations
are elevated in the brain and cerebrospinal fluid of schizophrenia
patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase
(KMO), a rate-limiting enzyme at the branching point of the kynurenine
pathway. Objectives To examine KMO messenger RNA expression and KMO
enzyme activity in postmortem tissue from the frontal eye field (FEF;
Brodmann area 6) obtained from schizophrenia individuals compared
with healthy control individuals and to explore the relationship
between KMO single-nucleotide polymorphisms and schizophrenia oculomotor
endophenotypes. Design Case-control postmortem and clinical study.
Setting Maryland Brain Collection, outpatient clinics. Participants
Postmortem specimens from schizophrenia patients (n = 32) and control
donors (n = 32) and a clinical sample of schizophrenia patients (n
= 248) and healthy controls (n = 228). Main Outcome Measures Comparison
of quantitative KMO messenger RNA expression and KMO enzyme activity
in postmortem FEF tissue between schizophrenia patients and controls
and association of KMO single-nucleotide polymorphisms with messenger
RNA expression in postmortem FEF and schizophrenia and oculomotor
endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed
response). Results In postmortem tissue, we found a significant and
correlated reduction in KMO gene expression and KMO enzyme activity
in the FEF in schizophrenia patients. In the clinical sample, KMO
rs2275163 was not associated with a diagnosis of schizophrenia but
showed modest effects on predictive pursuit and visuospatial working
memory endophenotypes. Conclusion Our results provide converging
lines of evidence implicating reduced KMO activity in the etiopathophysiology
of schizophrenia and related neurocognitive deficits.},
doi = {10.1001/archgenpsychiatry.2011.71},
eprint = {http://archpsyc.ama-assn.org/cgi/reprint/68/7/665.pdf},
url = {http://archpsyc.ama-assn.org/cgi/content/abstract/68/7/665}
}
@ARTICLE{Woo2009,
author = {Woo, Seonock and Yum, Seungshic and Park, Hong-Seog and Lee, Taek-Kyun
and Ryu, Jae-Chun},
title = {Effects of heavy metals on antioxidants and stress-responsive gene
expression in Javanese medaka (Oryzias javanicus)},
journal = {Comparative Biochemistry and Physiology Part C: Toxicology \& Pharmacology},
year = {2009},
volume = {149},
pages = {289--299},
number = {3},
month = apr,
abstract = {The differential expression of eight genes encoding stressor biomarkers
was investigated by real-time quantitative PCR in liver tissue extracted
from Javanese medaka after exposure to six heavy metals for 24 h.
OjaCAT transcription increased in a dose-dependent manner during
exposure to Cd, Cu, and Zn, but significantly decreased after exposure
to Ag, Cr, and Ni. OjaCYP1A transcription decreased drastically on
exposure to all heavy metals tested. OjaG6PD transcription increased
dramatically after exposure to low doses of Cu and Zn, but decreased
at high concentrations of these elements. No prominent changes in
OjaG6PD transcription were observed after exposure to Ag, Cd, Cr,
or Ni. OjaGPx mRNA expression was induced in the liver following
exposure to Ag, Cd, Cu, and Zn, but suppressed following exposure
to Cr and Ni. Exposure to all heavy metals increased transcription
of OjaGR and OjaGST in a dose-dependent manner. OjaSOD transcription
increased during exposure to Ag, Cd, Zn, and Cr, but showed no change
in response to Cu and Ni exposure. OjaUB expression was induced by
all doses of exposure. The transcriptional responses of these genes
to heavy metal exposure will provide the basis for a multi-biomarker
system that can be used for the biomonitoring of aquatic environments.},
issn = {1532-0456},
keywords = {Javanese medaka, Antioxidant genes, Stress-responsive genes, Heavy
metals, Real-time quantitative PCR, Multi-biomarker system},
url = {http://www.sciencedirect.com/science/article/B6W89-4T5JHXV-1/2/7425e289e6bdcb0cb91f23e7fca4fd60}
}
@ARTICLE{Wood2007,
author = {Wood, Andrew J. and Bourc'his, Deborah and Bestor, Timothy H. and
Oakey, Rebecca J.},
title = {Allele-specific demethylation at an imprinted mammalian promoter},
journal = {Nucleic Acids Res.},
year = {2007},
volume = {35},
pages = {7031--7039},
number = {20},
month = nov,
abstract = {A screen for imprinted genes on mouse Chromosome 7 recently identified
Inpp5f_v2, a paternally expressed retrogene lying within an intron
of Inpp5f. Here, we identify a novel paternally expressed variant
of the Inpp5f gene (Inpp5f_v3) that shows a number of unusual features.
Inpp5f_v3 initiates from a CpG-rich repeat region adjoining two B1
elements, despite previous reports that SINEs are generally excluded
from imprinted promoters. Accordingly, we find that the Inpp5f_v3
promoter acquires methylation around the time of implantation, when
many repeat families undergo de novo epigenetic silencing. Methylation
is then lost specifically on the paternally derived allele during
the latter stages of embryonic development, resulting in imprinted
transcriptional activation on the demethylated allele. Methylation
analyses in embryos lacking maternal methylation imprints suggest
that the primary imprinting mark resides within an intronic CpG island
[~]1 kb downstream of the Inpp5f_v3 transcriptional start site. These
data support the hypothesis that SINEs can influence gene expression
by attracting de novo methylation during development, a property
likely to explain their exclusion from other imprinted promoters.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/35/20/7031}
}
@ARTICLE{Wood2008,
author = {Wood, Andrew J. and Schulz, Reiner and Woodfine, Kathryn and Koltowska,
Katarzyna and Beechey, Colin V. and Peters, Jo and Bourc'his, Deborah
and Oakey, Rebecca J.},
title = {Regulation of alternative polyadenylation by genomic imprinting},
journal = {Genes \& Dev.},
year = {2008},
volume = {22},
pages = {1141--1146},
number = {9},
month = may,
abstract = {Maternally and paternally derived alleles can utilize different promoters,
but allele-specific differences in cotranscriptional processes have
not been reported. We show that alternative polyadenylation sites
at a novel murine imprinted gene (H13) are utilized in an allele-specific
manner. A differentially methylated CpG island separates polyA sites
utilized on maternal and paternal alleles, and contains an internal
promoter. Two genetic systems show that alleles lacking methylation
generate truncated H13 transcripts that undergo internal polyadenylation.
On methylated alleles, the internal promoter is inactive and elongation
proceeds to downstream polyadenylation sites. This demonstrates that
epigenetic modifications can influence utilization of alternative
polyadenylation sites.},
url = {http://genesdev.cshlp.org/cgi/content/abstract/22/9/1141}
}
@ARTICLE{Wood2012,
author = {Wood, Charles E. and Boue, Stephen M. and Collins-Burow, Bridgette
M. and Rhodes, Lyndsay V. and Register, Thomas C. and Cline, J. Mark
and Dewi, Fitriya N. and Burow, Matthew E.},
title = {Glyceollin-Elicited Soy Protein Consumption Induces Distinct Transcriptional
Effects As Compared to Standard Soy Protein},
journal = {Journal of Agricultural and Food Chemistry},
year = {2012},
volume = {60},
pages = {81-86},
number = {1},
abstract = { Glyceollins are stress-induced compounds in soybeans with bioactive
properties distinct from parent soy isoflavones. The goals of this
study were to evaluate the effects of dietary glyceollin-enriched
and standard soy protein isolates and identify candidate target pathways
of glyceollins on transcriptional profiles within mammary gland tissue.
Thirty female postmenopausal cynomolgus monkeys were randomized to
diets containing one of three protein sources for 3 weeks: (1) control
casein/lactalbumin (C/L), (2) standard soy protein containing 194
mg/day isoflavones (SOY), and (3) glyceollin-enriched soy protein
containing 189 mg/day isoflavones + 134 mg/day glyceollins (GLY).
All diets contained a physiologic dose of estradiol (E2) (1 mg/day).
All doses are expressed in human equivalents scaled by caloric intake.
Relative to the control C/L diet, the GLY diet resulted in greater
numbers of differentially regulated genes, which showed minimal overlap
with those of SOY. Effects of GLY related primarily to pathways involved
in lipid and carbohydrate metabolism, including peroxisome proliferator-activated
receptor (PPAR)-γ and AMP-activated protein kinase (AMPK) signaling,
adipocytokine expression, triglyceride synthesis, and lipase activity.
Notable genes upregulated by the GLY diet included PPAR-γ, adiponectin,
leptin, lipin 1, and lipoprotein lipase. The GLY diet also resulted
in lower serum total cholesterol, specifically nonhigh-density lipoprotein
cholesterol, and increased serum triglycerides as compared to the
C/L diet. No effects of GLY or SOY were seen on serum insulin, adipocytokines,
or vascular and bone turnover markers. These preliminary findings
suggest that glyceollin-enriched soy protein has divergent effects
from standard soy with some specificity for adipocyte activity and
nutrient metabolism. },
doi = {10.1021/jf2034863},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf2034863},
url = {http://pubs.acs.org/doi/abs/10.1021/jf2034863}
}
@ARTICLE{Wood2010a,
author = {Wood, Charles E. and Kaplan, Jay R. and Fontenot, M. Babette and
Williams, J. Koudy and Cline, J. Mark},
title = {Endometrial Profile of Tamoxifen and Low-Dose Estradiol Combination
Therapy},
journal = {Clin. Cancer Res.},
year = {2010},
volume = {16},
pages = {946--956},
number = {3},
month = feb,
abstract = {Purpose: Combination estrogen + progestin therapy has been associated
with increased breast cancer risk in postmenopausal women. Selective
estrogen receptor modulators (SERM) are potential alternatives to
progestins, although the endometrial safety of estrogen + SERM co-therapies
is not known. The goal of this study was to evaluate the endometrial
profile of low-dose estradiol and the SERM tamoxifen alone and in
combination. Experimental Design: Twenty-four postmenopausal female
cynomolgus macaques were randomized by social group to receive placebo,
low-dose micronized estradiol (E2; 0.25 mg/1,800 kcal), the SERM
tamoxifen (Tam; 20 mg/1,800 kcal), or E2 + Tam for 4 months in a
parallel-arm design. Results: Tamoxifen alone resulted in overlapping
but distinct effects compared with E2. Both E2 and Tam increased
uterine weight and endometrial thickness, whereas only E2 increased
endometrial proliferation. Morphologic effects were similar for Tam
and E2 + Tam, which both induced stromal fibrosis and cystic change.
Tamoxifen inhibited E2-induced proliferation and expression of genes
related to cell cycle progression while exhibiting mixed agonist
and antagonist effects on gene markers of estrogen receptor activity.
The gene expression profile for E2 + Tam was distinct from either
E2 or Tam alone but dominated by the Tam effect for estrogen-regulated
genes. Tam also attenuated E2 effects on both vaginal maturation
and cervical epithelial height. Conclusions: These findings characterize
a novel phenotype resulting from estrogen + SERM co-therapy. The
predominance of Tam effects on endometrial proliferation, morphology,
and transcriptional profiles suggests that endometrial risks for
E2 + Tam may be similar to Tam alone. Clin Cancer Res; 16(3); 946-56},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/16/3/946}
}
@ARTICLE{Wood2010,
author = {Wood, Henry M. and Belvedere, Ornella and Conway, Caroline and Daly,
Catherine and Chalkley, Rebecca and Bickerdike, Melissa and McKinley,
Claire and Egan, Phil and Ross, Lisa and Hayward, Bruce and Morgan,
Joanne and Davidson, Leslie and MacLennan, Ken and Ong, Thian K.
and Papagiannopoulos, Kostas and Cook, Ian and Adams, David J. and
Taylor, Graham R. and Rabbitts, Pamela},
title = {Using next-generation sequencing for high resolution multiplex analysis
of copy number variation from nanogram quantities of DNA from formalin-fixed
paraffin-embedded specimens},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {e151--},
number = {14},
month = aug,
abstract = {The use of next-generation sequencing technologies to produce genomic
copy number data has recently been described. Most approaches, however,
reply on optimal starting DNA, and are therefore unsuitable for the
analysis of formalin-fixed paraffin-embedded (FFPE) samples, which
largely precludes the analysis of many tumour series. We have sought
to challenge the limits of this technique with regards to quality
and quantity of starting material and the depth of sequencing required.
We confirm that the technique can be used to interrogate DNA from
cell lines, fresh frozen material and FFPE samples to assess copy
number variation. We show that as little as 5 ng of DNA is needed
to generate a copy number karyogram, and follow this up with data
from a series of FFPE biopsies and surgical samples. We have used
various levels of sample multiplexing to demonstrate the adjustable
resolution of the methodology, depending on the number of samples
and available resources. We also demonstrate reproducibility by use
of replicate samples and comparison with microarray-based comparative
genomic hybridization (aCGH) and digital PCR. This technique can
be valuable in both the analysis of routine diagnostic samples and
in examining large repositories of fixed archival material.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/14/e151}
}
@ARTICLE{Wood2011,
author = {Wood, Michael W. and Breitschwerdt, Edward B. and Gookin, Jody L.},
title = {Autocrine Effects of Interleukin-6 Mediate Acute-Phase Proinflammatory
and Tissue-Reparative Transcriptional Responses of Canine Bladder
Mucosa},
journal = {Infect. Immun.},
year = {2011},
volume = {79},
pages = {708--715},
number = {2},
month = feb,
abstract = {During early urinary tract infection (UTI) the interplay between invading
bacteria and the urothelium elicits a mucosal response aimed at clearing
infection. Unfortunately, the resultant inflammation and associated
local tissue injury are responsible for patient symptoms. Interleukin-6
(IL-6), a cytokine released during acute UTI, has both pro- and anti-inflammatory
effects on other body systems. Within the urothelium, the IL-6 native-tissue
origin, the target cell type(s), and ultimate effect of the cytokine
on target cells are largely unknown. In the present study we modeled
the UTI IL-6 response ex vivo using canine bladder mucosa mounted
in Ussing chambers to determine the inflammatory and reparative role
of IL-6. We demonstrated that uropathogenic Escherichia coli infection
stimulates the synthesis of IL-6 by all urothelial cell layers, with
the urothelial cells alone representing the only site of unequivocal
IL-6 receptor expression. Autocrine effects of IL-6 were supported
by the activation of urothelial STAT3 signaling and SOCS3 expression.
Using exogenous IL-6, a microarray approach, and quantitative reverse
transcriptase PCR (q-RT-PCR), 5 target genes (tumor necrosis factor
alpha, interleukin-1{beta}, matrix metallopeptidase 2, heparan sulfate
D-glucosaminyl 3-O-sulfotransferase 3A1, and hyaluronan synthase
2) that have direct or indirect roles in promoting a proinflammatory
state were identified. Two of these genes, heparan sulfate D-glucosaminyl
3-O-sulfotransferase 3A1 and hyaluronan synthase 2, are also potentially
important mediators of wound repair via the production of glycosaminoglycan
components. These findings suggest that IL-6 secretion during acute
UTI may serve a dual biological role by initiating the inflammatory
response while also repairing urothelial defenses.},
comment = {10.1128/IAI.01102-10},
url = {http://iai.asm.org/cgi/content/abstract/79/2/708}
}
@ARTICLE{Wood2008a,
author = {Wood, Shona H. and Clements, Dylan N. and McEwan, Neil A. and Nuttall,
Tim and Carter, Stuart D.},
title = {Reference genes for canine skin when using quantitative real-time
PCR},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {126},
pages = {392--395},
number = {3-4},
month = dec,
abstract = {Quantitative real-time PCR (qPCR) facilitates the quantification of
mRNA expression. Accurate qPCR analysis of gene expression requires
the normalisation of data using a reference or housekeeping gene
which is expressed at a similar level in all tissues tested. GAPDH
is the most well known and most widely used reference gene but many
papers have demonstrated that it is not stably expressed in different
tissues. The aim of this study was to measure reference gene stability
in canine skin using real-time qPCR. Skin samples from healthy control
dogs (n = 7) and dogs with atopic dermatitis (lesional skin n = 7
and non-lesional skin n = 7) were used to quantify seven reference
genes (IMP, CG14980, S7, HIRA, GAPDH, RPL13A and SDHA) in canine
whole skin. Three different statistical programs (Bestkeeper, GeNorm
and Normfinder) were used to assess the stability of the reference
genes. The results confirmed that GAPDH is not a stably expressed
reference gene in canine skin; this finding may influence interpretation
of previous qPCR studies on canine skin using this as a reference
gene. RPL13A and CG14980 were found to be the most stably expressed
genes in canine whole skin and would be more suitable as reference
genes in future studies.},
issn = {0165-2427},
keywords = {qPCR, Reference genes, GAPDH, Atopic dermatitis},
url = {http://www.sciencedirect.com/science/article/B6TD5-4T9VP3K-1/2/0dd75bbcb3032dd282cdf497d5e4310a}
}
@ARTICLE{Wood2009,
author = {Wood, Shona H. and Clements, Dylan N. and Ollier, William E. and
Nuttall, Tim and McEwan, Neil A. and Carter, Stuart D.},
title = {Gene expression in canine atopic dermatitis and correlation with
clinical severity scores},
journal = {J Dermatol Sci},
year = {2009},
volume = {55},
pages = {27--33},
number = {1},
month = jul,
abstract = {Canine atopic dermatitis (cAD) is a common condition in dogs that
may be a naturally occurring model for human atopic dermatitis (hAD).
Despite this, comparative research is limited, particularly into
the genetic background of cAD. 1.Measure candidate gene expression
in cAD skin using quantitative real time PCR (qPCR)2.Correlate gene
expression to clinical cAD scores (Canine Atopic Dermatitis Extent
and Severity Index [CADESI]-03 and intradermal allergen test [IDT]).
mRNA was extracted from biopsies of non-lesional and lesional skin
from atopic dogs, and healthy skin from non-atopic dogs. Gene expression
was quantified using qPCR, and compared between non-lesional atopic,
lesional atopic and healthy skin. Gene expression in atopic skin
was correlated with clinical severity (CADESI-03) and the number
of positive reactions on an IDT. Of the 20 quantified genes, 11 demonstrated
statistically significant altered mRNA expression between atopic
and healthy skin; dipeptidyl-peptidase-4 (DPP4), phosphatidylinositol-3,4,5-trisphosphate-5-phosphatase-2
(INPPL1), serine protease inhibitor kazal type-5 (SPINK5), sphingosine-1-phosphate
lyase-1 (SGPL1), peroxisome proliferator-activated receptor gamma
(PPARγ), S100 calcium-binding protein A8 (S100A8), Plakophilin-2
(PKP2), Periostin (POSTN), Cullin4A, TNF-α and metalloproteinase
inhibitor-1 (TIMP-1). Three genes correlated with CADESI-03: serum
amyloid A 1 (SAA-1), S100A8, and PKP2; and four with IDT results:
mast cell protease I (CMA1), SAA-1, S100A8 and SPINK5. Genes with
altered expression included those relevant to skin barrier formation
and immune function, suggesting both are relevant in the pathogenesis
of AD. Many of these genes reflect the proposed pathogenesis in hAD,
supporting the use of dogs as a model for hAD. Furthermore, these
genes may be considered suitable targets for future genetic and protein
function studies in human and canine AD.},
issn = {0923-1811},
keywords = {Atopic dermatitis, Canine, Severity scores, qPCR},
publisher = {Elsevier,},
refid = {S0923-1811(09)00093-0},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0923181109000930?showall=true}
}
@ARTICLE{Woodruff2005,
author = {Woodruff, Prescott G. and Koth, Laura L. and Yang, Yee Hwa and Rodriguez,
Madeleine W. and Favoreto, Silvio and Dolganov, Gregory M. and Paquet,
Agnes C. and Erle, David J.},
title = {A Distinctive Alveolar Macrophage Activation State Induced by Cigarette
Smoking},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2005},
volume = {172},
pages = {1383--1392},
number = {11},
month = dec,
abstract = {Rationale: Macrophages are believed to play a central role in emphysema
based largely on data from mouse models. However, the relevance of
these models to smoking-related lung disease in humans is uncertain.
Objectives: We sought to comprehensively characterize the effects
of smoking on gene expression in human alveolar macrophages and to
compare these with effects seen in transgenic mouse models of emphysema.
Methods: We used DNA microarrays with genomewide coverage to analyze
alveolar macrophages from 15 smokers, 15 nonsmokers, and 15 subjects
with asthma (disease control). Selected gene expression changes were
validated by polymerase chain reaction and ELISA. Expression changes
were compared with those identified by microarray analysis of interleukin-13-overexpressing
and integrin-{beta}6-deficient mice, which both develop emphysema.
Measurements and Main Results: All 15 smokers shared a common pattern
of macrophage gene expression that distinguished them from nonsmokers,
a finding not observed in subjects with asthma. We identified 110
genes as differentially expressed in smokers despite using conservative
statistical methods. Matrix metalloproteinase 12, a proteinase that
plays a critical role in mouse models, was the third most highly
induced gene in smokers (ninefold, p < 0.0001). However, most changes
in smokers were not reflected in mouse models. One such finding was
increased osteopontin expression in smokers (fourfold, p = 0.006),
which was confirmed at the protein level and correlated with the
degree of airway obstruction. Conclusions: Smoking induces a remarkably
consistent and distinctive pattern of alveolar macrophage activation.
These studies identify aspects of mouse models that are directly
relevant to human smokers and also reveal novel potential mediators
of smoking-related diseases.},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/172/11/1383}
}
@ARTICLE{Woods2009,
author = {Woods, Anita and James, Claudine G. and Wang, Guoyan and Dupuis,
Holly and Beier, Frank},
title = {Control of chondrocyte gene expression by actin dynamics: a novel
role of cholesterol/Ror-α signalling in endochondral bone growth},
journal = {Journal of Cellular and Molecular Medicine},
year = {2009},
volume = {13},
pages = {3497--3516},
number = {9b},
abstract = {Abstract Elucidating the signalling pathways that regulate chondrocyte
differentiation, such as the actin cytoskeleton and Rho GTPases,
during development is essential for understanding of pathological
conditions of cartilage, such as chondrodysplasias and osteoarthritis.
Manipulation of actin dynamics in tibia organ cultures isolated from
E15.5 mice results in pronounced enhancement of endochondral bone
growth and specific changes in growth plate architecture. Global
changes in gene expression were examined of primary chondrocytes
isolated from embryonic tibia, treated with the compounds cytochalasin
D, jasplakinolide (actin modifiers) and the ROCK inhibitor Y27632.
Cytochalasin D elicited the most pronounced response and induced
many features of hypertrophic chondrocyte differentiation. Bioinformatics
analyses of microarray data and expression validation by real-time
PCR and immunohistochemistry resulted in the identification of the
nuclear receptor retinoid related orphan receptor-α (Ror-α) as
a novel putative regulator of chondrocyte hypertrophy. Expression
of Ror-α target genes, (Lpl, fatty acid binding protein 4 [Fabp4],
Cd36 and kruppel-like factor 5 [Klf15]) were induced during chondrocyte
hypertrophy and by cytochalasin D and are cholesterol dependent.
Stimulation of Ror-α by cholesterol results in increased bone growth
and enlarged, rounded cells, a phenotype similar to chondrocyte hypertrophy
and to the changes induced by cytochalasin D, while inhibition of
cholesterol synthesis by lovastatin inhibits cytochalasin D induced
bone growth. Additionally, we show that in a mouse model of cartilage
specific (Col2-Cre) Rac1, inactivation results in increased Hif-1α
(a regulator of Rora gene expression) and Ror-α+ cells within hypertrophic
growth plates. We provide evidence that cholesterol signalling through
increased Ror-α expression stimulates chondrocyte hypertrophy and
partially mediates responses of cartilage to actin dynamics.},
issn = {1582-4934},
keywords = {chondrocytes, rho GTPases, actin cytoskeleton, microarray, cholesterol,
nuclear receptors, Ror-α, hypertrophy},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2009.00684.x}
}
@ARTICLE{Woods2009a,
author = {Woods, Courtney G. and Fu, Jingqi and Xue, Peng and Hou, Yongyong
and Pluta, Linda J. and Yang, Longlong and Zhang, Qiang and Thomas,
Russell S. and Andersen, Melvin E. and Pi, Jingbo},
title = {Dose-dependent transitions in Nrf2-mediated adaptive response and
related stress responses to hypochlorous acid in mouse macrophages},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {238},
pages = {27--36},
number = {1},
month = jul,
abstract = {Hypochlorous acid (HOCl) is potentially an important source of cellular
oxidative stress. Human HOCl exposure can occur from chlorine gas
inhalation or from endogenous sources of HOCl, such as respiratory
burst by phagocytes. Transcription factor Nrf2 is a key regulator
of cellular redox status and serves as a primary source of defense
against oxidative stress. We recently demonstrated that HOCl activates
Nrf2-mediated antioxidant response in cultured mouse macrophages
in a biphasic manner. In an effort to determine whether Nrf2 pathways
overlap with other stress pathways, gene expression profiling was
performed in RAW 264.7 macrophages exposed to HOCl using whole genome
mouse microarrays. Benchmark dose (BMD) analysis on gene expression
data revealed that Nrf2-mediated antioxidant response and protein
ubiquitination were the most sensitive biological pathways that were
activated in response to low concentrations of HOCl (< 0.35 mM).
Genes involved in chromatin architecture maintenance and DNA-dependent
transcription were also sensitive to very low doses. Moderate concentrations
of HOCl (0.35 to 1.4 mM) caused maximal activation of the Nrf2 pathway
and innate immune response genes, such as IL-1[beta], IL-6, IL-10
and chemokines. At even higher concentrations of HOCl (2.8 to 3.5 mM)
there was a loss of Nrf2-target gene expression with increased expression
of numerous heat shock and histone cluster genes, AP-1-family genes,
cFos and Fra1 and DNA damage-inducible Gadd45 genes. These findings
confirm an Nrf2-centric mechanism of action of HOCl in mouse macrophages
and provide evidence of interactions between Nrf2, inflammatory,
and other stress pathways.},
issn = {0041-008X},
keywords = {Nrf2, AP-1, NF-[kappa]B, Hypochlorous acid, Antioxidant response element,
Oxidative stress, Genomic profiling},
url = {http://www.sciencedirect.com/science/article/B6WXH-4W38RCP-1/2/c9f0acca6caadca7e541ddc992b1715b}
}
@ARTICLE{Woods2007,
author = {Woods, Courtney G. and Kosyk, Oksana and Bradford, Blair U. and Ross,
Pamela K. and Burns, Amanda M. and Cunningham, Michael L. and Qu,
Pingping and Ibrahim, Joseph G. and Rusyn, Ivan},
title = {Time course investigation of PPAR[alpha]- and Kupffer cell-dependent
effects of WY-14,643 in mouse liver using microarray gene expression},
journal = {Toxicology and Applied Pharmacology},
year = {2007},
volume = {225},
pages = {267--277},
number = {3},
month = dec,
abstract = {Administration of peroxisome proliferators to rodents causes proliferation
of peroxisomes, induction of [beta]-oxidation enzymes, hepatocellular
hypertrophy and hyperplasia, with chronic exposure ultimately leading
to hepatocellular carcinomas. Many responses associated with peroxisome
proliferators are nuclear receptor-mediated events involving peroxisome
proliferators-activated receptor alpha (PPAR[alpha]). A role for
nuclear receptor-independent events has also been shown, with evidence
of Kupffer cell-mediated free radical production, presumably through
NAPDH oxidase, induction of redox-sensitive transcription factors
involved in cytokine production and cytokine-mediated cell replication
following acute treatment with peroxisome proliferators in rodents.
Recent studies have demonstrated, by using p47phox-null mice which
are deficient in NADPH oxidase, that this enzyme is not related to
the phenotypic events caused by prolonged administration of peroxisome
proliferators. In an effort to determine the timing of the transition
from Kupffer cell-to PPAR[alpha]-dependent modulation of peroxisome
proliferator effects, gene expression was assessed in liver from
Ppar[alpha]-null, p47phox-null and corresponding wild-type mice following
treatment with 4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid
(WY-14,643) for 8 h, 24 h, 72 h, 1 week or 4 weeks. WY-14,643-induced
gene expression in p47phox-null mouse liver differed substantially
from wild-type mice at acute doses and striking differences in baseline
expression of immune related genes were evident. Pathway mapping
of genes that respond to WY-14,643 in a time- and dose-dependent
manner demonstrates suppression of immune response, cell death and
signal transduction and promotion of lipid metabolism, cell cycle
and DNA repair. Furthermore, these pathways were largely dependent
on PPAR[alpha], not NADPH oxidase demonstrating a temporal shift
in response to peroxisome proliferators. Overall, this study shows
that NADPH oxidase-dependent events, while detectable following acute
treatment, are transient. To the contrary, a strong PPAR[alpha]-specific
gene signature was evident in mice that were continually exposed
to WY-14,643.},
issn = {0041-008X},
keywords = {Peroxisome proliferators, PPAR[alpha], Kupffer cells, Toxicogenomics,
Microarrays},
url = {http://www.sciencedirect.com/science/article/B6WXH-4PNTW8B-2/2/67fa7ce5b8baccd7bf3bc26944603a25}
}
@ARTICLE{Woodward2010,
author = {Woodward, A. D. and Holcombe, S. J. and Steibel, J. P. and Staniar,
W. B. and Colvin, C. and Trottier, N. L.},
title = {Cationic and neutral amino acid transporter transcript abundances
are differentially expressed in the equine intestinal tract},
journal = {J Anim Sci},
year = {2010},
volume = {88},
pages = {1028--1033},
number = {3},
month = mar,
abstract = {To test the hypothesis that AA transporter transcripts are present
in the large intestine and similarly expressed along the intestinal
tract, mRNA abundance of candidate AA transporter genes solute carrier
(SLC) family 7, member 9 (SLC7A9), SLC7A1, SLC7A8, and SLC43A1 encoding
for b0,+-type AA transporter (b0,+AT), cationic AA transporter-1
(CAT-1), L-type AA transporter-2 (LAT-2), and L-type AA transporter-3
(LAT-3), respectively, was determined in small and large intestinal
segments of the horse. Mucosa was collected from the equine small
(jejunum and ileum) and large intestine (cecum, left ventral colon,
and left dorsal colon), flash frozen in liquid nitrogen, and stored
at -80{degrees}C. Messenger RNA was isolated from tissue samples,
followed by manufacture of cDNA. Relative quantitative reverse transcription-PCR
was conducted using the 2-{Delta}{Delta}CT method, with glyceraldehyde-3-phosphate
dehydrogenase serving as the housekeeping gene. Compared with the
jejunum, cationic and neutral AA transporter SLC7A9 mRNA abundance
was similar in the ileum, cecum, and large intestinal segments. Compared
with the jejunum, cationic AA transporter SLC7A1 mRNA abundance was
similar in the ileum and decreased in the cecum, left ventral colon,
and left dorsal colon (P < 0.001). Neutral AA transporter SLC7A8
mRNA abundance decreased from the cranial to caudal end of the intestinal
tract (P < 0.001). Neutral AA transporter SLC43A1 mRNA abundance
was similar in the ileum and left dorsal colon and increased in the
cecum (P < 0.01) and left ventral colon (P < 0.1) compared with the
jejunum. Cationic and neutral AA transporter SLC7A9 mRNA abundance
was similarly expressed in the large compared with small intestine,
whereas cationic AA transporter SLC7A1 was of low abundance in the
large intestine; neutral AA transporters SLC7A8 and SLC43A1 were
differentially expressed with decreased abundance of SLC7A8 and increased
abundance of SLC43A1 in the large intestine. Results indicate that
the large intestine might contribute to both cationic and neutral
AA uptake and absorption predominantly via transporters LAT-3 and
b0,+AT.},
url = {http://jas.fass.org/cgi/content/abstract/88/3/1028}
}
@ARTICLE{Worden2005,
author = {Worden, Brian and Yang, Xin Ping and Lee, Tin Lap and Bagain, Lorena
and Yeh, Ning T. and Cohen, Joshua G. and Van Waes, Carter and Chen,
Zhong},
title = {Hepatocyte Growth Factor/Scatter Factor Differentially Regulates
Expression of Proangiogenic Factors through Egr-1 in Head and Neck
Squamous Cell Carcinoma},
journal = {Cancer Res.},
year = {2005},
volume = {65},
pages = {7071--7080},
number = {16},
month = aug,
abstract = {Hepatocyte growth factor/scatter factor (HGF) and the angiogenesis
factors platelet-derived growth factors (PDGF), vascular endothelial
growth factor (VEGF), and interleukin-8 (IL-8) are found in elevated
concentrations in serum or tumor tissue of patients with head and
neck squamous cell carcinomas (HNSCC), suggesting these factors may
be coregulated. A cDNA microarray analysis for HGF-inducible genes
revealed that HGF also modulates PDGFA expression, a gene recently
shown to be inducible by the transcription factor, early growth response-1
(Egr-1). In the present study, we investigated the potential role
of HGF-induced Egr-1 in expression of PDGF, VEGF, and IL-8. HGF induced
expression of all three factors and Egr-1 expression and DNA-binding
activity. The analysis of promoter sequences showed putative Egr-1
binding sites in the PDGFA or VEGF but not in the IL-8 promoter,
and HGF-induced Egr-1-binding activity was confirmed by chromatin
immunoprecipitation (ChIP) assay. The maximal basal and HGF-induced
promoter activity for the PDGFA gene existed within -630 bp of the
promoter region, and overexpression of Egr-1 significantly increased
such activity. Consistent with this, expression of PDGFA and VEGF
but not IL-8 showed corresponding differences with Egr-1 expression
in HNSCC tumor specimens and were strongly suppressed by transfection
of Egr-1-antisense or small interference RNA (siRNA) oligonucleotides.
HGF-induced expression of Egr-1, PDGFA, and VEGF was suppressed by
pharmacologic and siRNA inhibitors of mitogen-activated protein kinase
kinase 1/2 (MEK1/2) and protein kinase C (PKC) pathways. We conclude
that the HGF-induced activation of transcription factor Egr-1 by
MEK1/2- and PKC-dependent mechanisms differentially contributes to
expression of PDGF and VEGF, which are important angiogenesis factors
and targets for HNSCC therapy.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/16/7071}
}
@ARTICLE{Worku2009,
author = {Worku, M. and Morris, A.},
title = {Binding of different forms of lipopolysaccharide and gene expression
in bovine blood neutrophils},
journal = {J Dairy Sci},
year = {2009},
volume = {92},
pages = {3185--3193},
number = {7},
month = jul,
abstract = {The objective of this study was to evaluate the effect of smooth (S)
and rough (R) forms of lipopolysaccharide (LPS) on gene expression
in bovine blood neutrophils. Isolated neutrophils (107 cells/mL)
were treated with Escherichia coli LPS serotype O111:B4 (S+R) and
R forms (Ra, Rd, or Rc). Flow cytometry was used to assess surface
expression of toll-like receptor 4 (TLR-4). Specific primers for
IL-8, tumor necrosis factor-{alpha} (TNF-{alpha}), IL-1{beta}, cluster
of differentiation antigen 14 (CD14), and natural resistance associated
macrophage protein 1 (Nramp1) were used to assess transcription.
Secretion of IL-8, TNF-{alpha}, or IL-1{beta} was determined using
ELISA kits. Both S and R forms of LPS bound to neutrophils. Exposure
induced increased surface expression of TLR-4. No TLR-4 or CD14 mRNA
was detected but transcripts for IL-8, TNF-{alpha}, IL-1{beta}, and
Nramp1 were detected. Secretion of IL-8 and TNF-{alpha} but not IL-1{beta}
was observed following treatment with R forms of LPS. The longest
R form tested (Ra) increased RNA purity and IL-8 and TNF-{alpha}
secretion in bovine neutrophils. The Rd form increased TLR-4 expression
and reduced IL-8 and TNF-{alpha} secretion. Exposure to LPS induced
increased cell surface expression of TLR-4 and enhanced expression
of IL-8 genes. Enhanced TLR-4 activity by LPS was not dependent on
transcriptional activation. Recruitment of TLR-4 to the cell membrane
may account for increased cell surface expression. A CD14-independent,
TLR-4-dependent pathway may be important in the response to different
forms of LPS by bovine neutrophils.},
url = {http://jds.fass.org/cgi/content/abstract/92/7/3185}
}
@ARTICLE{Woroniecka2011,
author = {Woroniecka, Karolina I. and Park, Ae Seo Deok and Mohtat, Davoud
and Thomas, David B. and Pullman, James M. and Susztak, Katalin},
title = {Transcriptome Analysis of Human Diabetic Kidney Disease},
journal = {Diabetes},
year = {2011},
volume = {60},
pages = {2354-2369},
number = {9},
abstract = {OBJECTIVEDiabetic kidney disease (DKD) is the single leading cause
of kidney failure in the U.S., for which a cure has not yet been
found. The aim of our study was to provide an unbiased catalog of
gene-expression changes in human diabetic kidney biopsy samples.
RESEARCH DESIGN AND METHODSAffymetrix expression arrays were used
to identify differentially regulated transcripts in 44 microdissected
human kidney samples. DKD samples were significant for their racial
diversity and decreased glomerular filtration rate (~25-35 mL/min).
Stringent statistical analysis, using the Benjamini-Hochberg corrected
two-tailed t test, was used to identify differentially expressed
transcripts in control and diseased glomeruli and tubuli. Two different
web-based algorithms were used to define differentially regulated
pathways. RESULTSWe identified 1,700 differentially expressed probesets
in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets
were commonly differentially expressed in both compartments. Pathway
analysis highlighted the regulation of Ras homolog gene family member
A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial
growth factor signaling in DKD glomeruli. The tubulointerstitial
compartment showed strong enrichment for inflammation-related pathways.
The canonical complement signaling pathway was determined to be statistically
differentially regulated in both DKD glomeruli and tubuli and was
associated with increased glomerulosclerosis even in a different
set of DKD samples. CONCLUSIONSOur studies have cataloged gene-expression
regulation and identified multiple novel genes and pathways that
may play a role in the pathogenesis of DKD or could serve as biomarkers.},
doi = {10.2337/db10-1181},
eprint = {http://diabetes.diabetesjournals.org/cgi/reprint/60/9/2354.pdf},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/60/9/2354}
}
@ARTICLE{Worschech2009,
author = {Worschech, Andrea and Chen, Nanhai and Yu, Yong and Zhang, Qian and
Pos, Zoltan and Weibel, Stephanie and Raab, Viktoria and Sabatino,
Marianna and Monaco, Alessandro and Liu, Hui and Monsurró, Vladia
and Buller, R Mark and Stroncek, David and Wang, Ena and Szalay,
Aladar and Marincola, Francesco},
title = {Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals
the immunologic facet of oncolytic therapy},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {301},
number = {1},
abstract = {BACKGROUND:GLV-1h68 is an attenuated recombinant vaccinia virus (VACV)
that selectively colonizes established human xenografts inducing
their complete regression.RESULTS:Here, we explored xenograft/VACV/host
interactions in vivo adopting organism-specific expression arrays
and tumor cell/VACV in vitro comparing VACV replication patterns.
There were no clear-cut differences in vitro among responding and
non-responding tumors, however, tumor rejection was associated in
vivo with activation of interferon-stimulated genes (ISGs) and innate
immune host's effector functions (IEFs) correlating with VACV colonization
of the xenografts. These signatures precisely reproduce those observed
in humans during immune-mediated tissue-specific destruction (TSD)
that causes tumor or allograft rejection, autoimmunity or clearance
of pathogens. We recently defined these common pathways in the "immunologic
constant of rejection" hypothesis (ICR).CONCLUSION:This study provides
the first prospective validation of a universal mechanism associated
with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering
a promising therapy of established cancers, may represent a reliable
pre-clinical model to test therapeutic strategies aimed at modulating
the central pathways leading to TSD; this information may lead to
the identification of principles that could refine the treatment
of cancer and chronic infection by immune stimulation or autoimmunity
and allograft rejection through immune tolerance.},
doi = {10.1186/1471-2164-10-301},
issn = {1471-2164},
pubmedid = {19583830},
url = {http://www.biomedcentral.com/1471-2164/10/301}
}
@ARTICLE{Worschech2008,
author = {Worschech, Andrea and Kmieciak, Maciej and Knutson, Keith L. and
Bear, Harry D. and Szalay, Aladar A. and Wang, Ena and Marincola,
Francesco M. and Manjili, Masoud H.},
title = {Signatures Associated with Rejection or Recurrence in HER-2/neu-Positive
Mammary Tumors},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {2436--2446},
number = {7},
month = apr,
abstract = {We have previously shown T-cell-mediated rejection of the neu-overexpressing
mammary carcinoma cells (MMC) in wild-type FVB mice. However, following
rejection of primary tumors, a fraction of animals experienced a
recurrence of a neu antigen-negative variant (ANV) of MMC (tumor
evasion model) after a long latency period. In the present study,
we determined that T cells derived from wild-type FVB mice can specifically
recognize MMC by secreting IFN-{gamma} and can induce apoptosis of
MMC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors
and cannot reject it (tumor tolerance model). To dissect the mechanisms
associated with rejection or tolerance of MMC tumors, we compared
transcriptional patterns within the tumor microenvironment of MMC
undergoing rejection with those that resisted it either because of
tumor evasion/antigen loss recurrence (ANV tumors) or because of
intrinsic tolerance mechanisms displayed by the transgenic mice.
Gene profiling confirmed that immune rejection is primarily mediated
through activation of IFN-stimulated genes and T-cell effector mechanisms.
The tumor evasion model showed combined activation of Th1 and Th2
with a deviation toward Th2 and humoral immune responses that failed
to achieve rejection likely because of lack of target antigen. Interestingly,
the tumor tolerance model instead displayed immune suppression pathways
through activation of regulatory mechanisms that included in particular
the overexpression of interleukin-10 (IL-10), IL-10 receptor, and
suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data
provide a road map for the identification of novel biomarkers of
immune responsiveness in clinical trials. [Cancer Res 2008;68(7):2436-46]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/7/2436}
}
@ARTICLE{Wotschofsky2011,
author = {Zofia Wotschofsky and Helmuth-Alexander Meyer and Monika Jung and
Annika Fendler and Ina Wagner and Carsten Stephan and Jonas Busch
and Andreas Erbersdobler and Alexander C. Disch and Hans-Joachim
Mollenkopf and Klaus Jung},
title = {Reference genes for the relative quantification of microRNAs in renal
cell carcinomas and their metastases},
journal = {Analytical Biochemistry},
year = {2011},
volume = {417},
pages = {233 - 241},
number = {2},
abstract = {To obtain accurate results in miRNA expression changes between different
sample sets using real-time quantitative polymerase chain reaction
(RT-qPCR) analyses, normalization to reference genes that are stably
expressed across the sample sets is generally used. A literature
search of miRNA expression studies in renal cell carcinoma (RCC)
proved that non-miRNAs such as small RNAs or mRNAs have most frequently
been used without preceding validation of their suitability. In this
study, the most stably expressed miRNAs were ascertained from microarray-based
data of miRNA expression in nonmalignant and malignant samples from
clear cell RCC and from corresponding distant RCC metastases using
the geNorm and NormFinder algorithms. Validation experiments with
RT-qPCR were performed for the four best-ranked miRNAs (miR-28, miR-103,
miR-106a, miR-151) together with the small RNU6B, RNU44, and RNU48
mostly described in literature. miR-28, miR-103, miR-106a, and RNU48
were proved as the most stably expressed genes. miR-28 is recommended
as normalizer if only a single reference gene can be used, while
the combinations of miR-28 and miR-103 or of miR-28, miR-103, and
miR-106a, respectively, are preferred. RNU6B most frequently used
as normalizer in miRNA expression studies should be abandoned in
order to avoid misleading results.},
doi = {10.1016/j.ab.2011.06.009},
issn = {0003-2697},
keywords = {MicroRNAs},
url = {http://www.sciencedirect.com/science/article/pii/S0003269711003939}
}
@ARTICLE{Wout2003,
author = {van 't Wout, Angelique B. and Lehrman, Ginger K. and Mikheeva, Svetlana
A. and O'Keeffe, Gemma C. and Katze, Michael G. and Bumgarner, Roger
E. and Geiss, Gary K. and Mullins, James I.},
title = {Cellular Gene Expression upon Human Immunodeficiency Virus Type 1
Infection of CD4+-T-Cell Lines},
journal = {J. Virol.},
year = {2003},
volume = {77},
pages = {1392--1402},
number = {2},
month = jan,
abstract = {The expression levels of [~]4,600 cellular RNA transcripts were assessed
in CD4+-T-cell lines at different times after infection with human
immunodeficiency virus type 1 strain BRU (HIV-1BRU) using DNA microarrays.
We found that several classes of genes were inhibited by HIV-1BRU
infection, consistent with the G2 arrest of HIV-1-infected cells
induced by Vpr. These included genes involved in cell division and
transcription, a family of DEAD-box proteins (RNA helicases), and
all genes involved in translation and splicing. However, the overall
level of cell activation and signaling was increased in infected
cells, consistent with strong virus production. These included a
subgroup of transcription factors, including EGR1 and JUN, suggesting
they play a specific role in the HIV-1 life cycle. Some regulatory
changes were cell line specific; however, the majority, including
enzymes involved in cholesterol biosynthesis, of changes were regulated
in most infected cell lines. Compendium analysis comparing gene expression
profiles of our HIV-1 infection experiments to those of cells exposed
to heat shock, interferon, or influenza A virus indicated that HIV-1
infection largely induced specific changes rather than simply activating
stress response or cytokine response pathways. Thus, microarray analysis
confirmed several known HIV-1 host cell interactions and permitted
identification of specific cellular pathways not previously implicated
in HIV-1 infection. Continuing analyses are expected to suggest strategies
for impacting HIV-1 replication in vivo by targeting these pathways.},
url = {http://jvi.asm.org/cgi/content/abstract/77/2/1392}
}
@ARTICLE{Wray2003,
author = {Wray, Curtis J. and Mammen, Joshua M. V. and Hershko, Dan D. and
Hasselgren, Per-Olof},
title = {Sepsis upregulates the gene expression of multiple ubiquitin ligases
in skeletal muscle},
journal = {The International Journal of Biochemistry \& Cell Biology},
year = {2003},
volume = {35},
pages = {698--705},
number = {5},
month = may,
abstract = {Muscle wasting during sepsis reflects increased expression and activity
of the ubiquitin-proteasome proteolytic pathway and is at least in
part mediated by glucocorticoids. The ubiquitination of proteins
destined to be degraded by the proteasome is regulated by multiple
enzymes, including ubiquitin ligases. We tested the hypothesis that
sepsis upregulates the gene expression of the newly described ubiquitin
ligases, MuRF1 and atrogin-1/MAFbx. Sepsis was induced in rats by
cecal ligation and puncture. Control rats were sham-operated. In
some experiments, rats were treated with the glucocorticoid receptor
antagonist RU 38486 before induction of sepsis. At various time points
after induction of sepsis, mRNA levels for MuRF1 and atrogin-1/MAFbx
were determined in extensor digitorum longus muscles by real-time
PCR. Sepsis resulted in a 10-16-fold increase in gene expression
of the ubiquitin ligases studied here. These changes were much greater
than those observed previously for another ubiquitin ligase, E3[alpha],
in muscle during sepsis. Treatment of rats with RU 38486 prevented
the sepsis-induced increase in mRNA levels for MuRF1 and atrogin-1/MAFbx,
suggesting that glucocorticoids participate in the upregulation of
these genes in muscle during sepsis. The present results lend further
support to the concept that the ubiquitin-proteasome pathway plays
an important role in sepsis-induced muscle proteolysis and suggest
that multiple ubiquitin ligases may participate in the development
of muscle wasting during sepsis.},
booktitle = {The proteasome in the regualtion of cell function},
issn = {1357-2725},
keywords = {Muscle wasting, Ubiquitin, Proteasome, Ubiquitin ligase, Sepsis, Cachexia,
Catabolism},
url = {http://www.sciencedirect.com/science/article/B6TCH-47TFCJF-1/2/099f30e08aa3662fc8e4b74746340429}
}
@ARTICLE{Wray2002,
author = {Wray, Curtis J and Tomkinson, Birgitta and Robb, Bruce W and Hasselgren,
Per-Olof},
title = {Tripeptidyl-peptidase II expression and activity are increased in
skeletal muscle during sepsis},
journal = {Biochemical and Biophysical Research Communications},
year = {2002},
volume = {296},
pages = {41--47},
number = {1},
month = aug,
abstract = {Ubiquitin-proteasome-dependent protein degradation plays a central
role in sepsis-induced muscle wasting. Because the proteasome degrades
proteins into small peptides rather than free amino acids, it is
likely that additional mechanisms downstream of the proteasome are
involved in sepsis-induced muscle proteolysis. Recent studies suggest
that the extralysosomal peptidase tripeptidyl-peptidase II (TPP II)
degrades peptides generated by the proteasome. We hypothesized that
TPP II expression and activity are increased in skeletal muscle during
sepsis. Sepsis was induced in rats by cecal ligation and puncture.
Control rats were sham-operated. TPP II activity was determined by
using the specific substrate Ala-Ala-Phe-7-amido-4-methylcoumarin
(AAF-AMC). TPP II protein and gene expression were determined by
Western blot and real-time PCR, respectively. Sepsis resulted in
increased activity and protein and gene expression of TPP II in extensor
digitorum longus muscles. This result was blunted by the glucocorticoid
receptor antagonist RU 38486, indicating that glucocorticoids participate
in the upregulation of TPP II in skeletal muscle during sepsis. The
results suggest that proteolytic mechanisms downstream of the proteasome
may be important for the complete degradation of muscle proteins
during sepsis.},
issn = {0006-291X},
keywords = {Muscle wasting, Ubiquitin, Proteasome, Glucocorticoids},
url = {http://www.sciencedirect.com/science/article/B6WBK-46WFW1S-8/2/8f05870b1fd29b3a0c39151ca65c0dea}
}
@ARTICLE{Wredenberg2006,
author = {Wredenberg, Anna and Freyer, Christoph and Sandström, Marie E. and
Katz, Abram and Wibom, Rolf and Westerblad, Håkan and Larsson, Nils-Göran},
title = {Respiratory chain dysfunction in skeletal muscle does not cause insulin
resistance},
journal = {Biochemical and Biophysical Research Communications},
year = {2006},
volume = {350},
pages = {202--207},
number = {1},
month = nov,
abstract = {Insulin resistance in skeletal muscle is a characteristic feature
of diabetes mellitus type 2 (DM2). Several lines of circumstantial
evidence suggest that reduced mitochondrial oxidative phosphorylation
capacity in skeletal muscle is a primary defect causing insulin resistance
and subsequent development of DM2. We have now experimentally tested
this hypothesis by characterizing glucose homeostasis in tissue-specific
knockout mice with progressive respiratory chain dysfunction selectively
in skeletal muscle. Surprisingly, these knockout mice are not diabetic
and have an increased peripheral glucose disposal when subjected
to a glucose tolerance test. Studies of isolated skeletal muscle
from knockout animals show an increased basal glucose uptake and
a normal increase of glucose uptake in response to insulin. In summary,
our findings indicate that mitochondrial dysfunction in skeletal
muscle is not a primary etiological event in DM2.},
issn = {0006-291X},
keywords = {Mitochondria, mtDNA, Insulin resistance, Diabetes, Respiratory chain,
Oxidative phosphorylation},
url = {http://www.sciencedirect.com/science/article/B6WBK-4KXDNJP-7/2/5050c17cce163cd348549bf0bbb7bb65}
}
@ARTICLE{Wright2008,
author = {Wright, Christopher and Bergstrom, Donald and Dai, Hongyue and Marton,
Matthew and Morris, Mark and Tokiwa, George and Wang, Yanqun and
Fare, Thomas},
title = {Characterization of Globin RNA Interference in Gene Expression Profiling
of Whole-Blood Samples},
journal = {Clin. Chem.},
year = {2008},
volume = {54},
pages = {396--405},
number = {2},
month = feb,
abstract = {Background: Blood-based biomarker discovery with gene expression profiling
has been hampered by interference from endogenous, highly abundant
{alpha}- and {beta}-globin transcripts. We describe a means to quantify
the interference of globin transcripts on profiling and the effectiveness
of globin transcript mitigation by (a) defining and characterizing
globin interference, (b) reproducing globin interference with synthetic
transcripts, and (c) using ROC curves to measure sensitivity and
specificity for a protocol for removing {alpha}- and {beta}-globin
transcripts. Methods: We collected blood at 2 sites and extracted
total RNA in PreAnalytiX PAXgene tubes. As a reference for characterizing
interference, we supplemented aliquots of total RNA with synthesized
globin transcripts and total RNA from human brain. Selected aliquots
were processed with Ambion GLOBINclear to remove globin transcripts.
All aliquots were labeled and hybridized to Agilent DNA microarrays
by means of pooling schemes designed to quantify the mitigation of
globin interference and to titrate gene expression signatures. Quantitative
reverse transcription-PCR data were generated for comparison with
microarray results. Results: Our supplementation and pooling strategy
for comparing the microarray data among samples demonstrated that
mitigation could reduce an interference signature of >1000 genes
to approximately 200. Analysis of samples of endogenous globin transcripts
supplemented with brain RNA indicated that results obtained with
the GLOBINclear treatment approach those of peripheral blood mononuclear
cell preparations. Conclusion: We confirmed that both the absolute
concentrations of globin transcripts and differences in transcript
concentrations within a sample set are factors that cause globin
interference (Genes Immun 2005;6:588-95). The methods and transcripts
we have developed may be useful for quantitatively characterizing
globin mRNA interference and its mitigation.},
url = {http://www.clinchem.org/cgi/content/abstract/54/2/396}
}
@ARTICLE{Wright2011a,
author = {Wright, Caroline F. and Morelli, Marco J. and Thebaud, Gael and Knowles,
Nick J. and Herzyk, Pawel and Paton, David J. and Haydon, Daniel
T. and King, Donald P.},
title = {Beyond the Consensus: Dissecting Within-Host Viral Population Diversity
of Foot-and-Mouth Disease Virus by Using Next-Generation Genome Sequencing},
journal = {J. Virol.},
year = {2011},
volume = {85},
pages = {2266--2275},
number = {5},
month = mar,
abstract = {The diverse sequences of viral populations within individual hosts
are the starting material for selection and subsequent evolution
of RNA viruses such as foot-and-mouth disease virus (FMDV). Using
next-generation sequencing (NGS) performed on a Genome Analyzer platform
(Illumina), this study compared the viral populations within two
bovine epithelial samples (foot lesions) from a single animal with
the inoculum used to initiate experimental infection. Genomic sequences
were determined in duplicate sequencing runs, and the consensus sequence
of the inoculum determined by NGS was identical to that previously
determined using the Sanger method. However, NGS revealed the fine
polymorphic substructure of the viral population, from nucleotide
variants present at just below 50% frequency to those present at
fractions of 1%. Some of the higher-frequency polymorphisms identified
encoded changes within codons associated with heparan sulfate binding
and were present in both foot lesions, revealing intermediate stages
in the evolution of a tissue culture-adapted virus replicating within
a mammalian host. We identified 2,622, 1,434, and 1,703 polymorphisms
in the inoculum and in the two foot lesions, respectively: most of
the substitutions occurred in only a small fraction of the population
and represented the progeny from recent cellular replication prior
to onset of any selective pressures. We estimated the upper limit
for the genome-wide mutation rate of the virus within a cell to be
7.8 x 10-4 per nucleotide. The greater depth of detection achieved
by NGS demonstrates that this method is a powerful and valuable tool
for the dissection of FMDV populations within hosts.},
comment = {10.1128/JVI.01396-10},
url = {http://jvi.asm.org/cgi/content/abstract/85/5/2266}
}
@ARTICLE{Wright2010,
author = {Wright, Casey M. and Larsen, Jill E. and Hayward, Nicholas K. and
Martins, Maria U. and Tan, Maxine E. and Davidson, Morgan R. and
Savarimuthu, Santiyagu M. and McLachlan, Rebecca E. and Passmore,
Linda H. and Windsor, Morgan N. and Clarke, Belinda E. and Duhig,
Edwina E. and Yang, Ian A. and Bowman, Rayleen V. and Fong, Kwun
M.},
title = {ADAM28: A potential oncogene involved in asbestos-related lung adenocarcinomas},
journal = {Genes Chromosom. Cancer},
year = {2010},
volume = {49},
pages = {688--698},
number = {8},
abstract = {Abstract 10.1002/gcc.20779.abs Asbestos-related lung cancer accounts
for 4–12% of all lung cancers worldwide. Since putative mechanisms
of carcinogenesis differ between asbestos and tobacco induced lung
cancers, tumors induced by the two agents may be genetically distinct.
To identify gene expression biomarkers associated with asbestos-related
lung tumorigenicity we performed gene expression array analysis on
tumors of 36 patients with primary lung adenocarcinoma, comparing
12 patients with lung asbestos body counts above levels associated
with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma)
with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos
related lung cancer-adenocarcinoma). Genes differentially expressed
between ARLC-AC and NARLC-AC were identified on fold change and P
value, and then prioritized using gene ontology. Candidates included
ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these
six genes was technically and biologically replicated by qRT-PCR
in the training set and biologically validated in three independent
test sets. ADAM28, encoding a disintegrin and metalloproteinase domain
protein that interacts with integrins, was consistently upregulated
in ARLC across all four datasets. Further studies are being designed
to investigate the possible role of this gene in asbestos lung tumorigenicity,
its potential utility as a marker of asbestos related lung cancer
for purposes of causal attribution, and its potential as a treatment
target for lung cancers arising in asbestos exposed persons. © 2010
Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20779}
}
@ARTICLE{Wright2012,
author = {Wright, Catherine S. and Pollok, Simone and Flint, David J. and Brandner,
Johanna M. and Martin, Patricia E.M.},
title = {The connexin mimetic peptide Gap27 increases human dermal fibroblast
migration in hyperglycemic and hyperinsulinemic conditions in vitro},
journal = {Journal of Cellular Physiology},
year = {2012},
volume = {227},
pages = {77--87},
number = {1},
abstract = {Significant increases in skin wound healing rates occur by reducing
connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic
peptide targeted to the second extracellular loop of Cx43, which
inhibits CMC, increases migration of human keratinocytes and dermal
fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic
and hyperinsulinemic in vitro environment, cell migration, gap junction,
and Cx hemichannel functionality and cell–substrate adhesion assays
were performed on human dermal fibroblasts and diabetic fibroblast
and keratinocytes. To investigate fibroblast genes involved in these
processes, extra-cellular matrix (ECM) and adhesion gene expression
was determined with a PCR array. Gap27 increased fibroblast migration
in both euglycemia/euinsulinemia and hyperglycemia/hyperinsulinemia,
and influenced migration in diabetic keratinocytes. Hyperglycemia/hyperinsulinemia
reduced gap junction coupling in fibroblasts and Gap27 reduced CMC
and cell adhesion to substrata in fibroblasts cultured in high glucose.
Migrating dermal fibroblast ECM and cell adhesion genes were found
to be differentially regulated by Gap27 in euglycemia and hyperglycemia.
The PCR array showed that Gap27 upregulated 34 genes and downregulated
1 gene in euglycemic migrating fibroblasts. By contrast in hyperglycemia,
Gap27 upregulated 1 gene and downregulated 9 genes. In euglycemic
conditions, Gap27 induced upregulation of genes associated with ECM
remodeling, whereas in hyperglycemia, ECM component genes were downregulated
by Gap27. Thus, Gap27 improves cell migration during scrape-wound
repair in hyperglycemia/hyperinsulinemia conditions in vitro, although
migration of diabetic cells is less influenced. Our results suggest
that this increase in motility may occur by decreasing gap junction
and hemichannel activity and altering gene expression in the adhesion
and ECM pathway. J. Cell. Physiol. 227: 77–87, 2012. © 2011 Wiley
Periodicals, Inc.},
doi = {10.1002/jcp.22705},
issn = {1097-4652},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcp.22705}
}
@ARTICLE{Wright2011,
author = {Emma M.M. Burkitt Wright and Helen L. Spencer and Sarah B. Daly
and Forbes D.C. Manson and Leo A.H. Zeef and Jill Urquhart and
Nicoletta Zoppi and Richard Bonshek and Ioannis Tosounidis and Meyyammai
Mohan and Colm Madden and Annabel Dodds and Kate E. Chandler and
Siddharth Banka and Leon Au and Jill Clayton-Smith and Naz Khan and
Leslie G. Biesecker and Meredith Wilson and Marianne Rohrbach and
Marina Colombi and Cecilia Giunta and Graeme C.M. Black},
title = {Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway
Regulating Extracellular Matrix Development and Maintenance},
journal = {The American Journal of Human Genetics},
year = {2011},
volume = {88},
pages = {767 - 777},
number = {6},
abstract = {Extreme corneal fragility and thinning, which have a high risk of
catastrophic spontaneous rupture, are the cardinal features of brittle
cornea syndrome (BCS), an autosomal-recessive generalized connective
tissue disorder. Enucleation is frequently the only management option
for this condition, resulting in blindness and psychosocial distress.
Even when the cornea remains grossly intact, visual function could
also be impaired by a high degree of myopia and keratoconus. Deafness
is another common feature and results in combined sensory deprivation.
Using autozygosity mapping, we identified mutations in PRDM5 in families
with BCS. We demonstrate that regulation of expression of extracellular
matrix components, particularly fibrillar collagens, by PRDM5 is
a key molecular mechanism that underlies corneal fragility in BCS
and controls normal corneal development and maintenance. ZNF469,
encoding a zinc finger protein of hitherto undefined function, has
been identified as a quantitative trait locus for central corneal
thickness, and mutations in this gene have been demonstrated in Tunisian
Jewish and Palestinian kindreds with BCS. We show that ZNF469 and
PRDM5, two genes that when mutated cause BCS, participate in the
same regulatory pathway.},
doi = {10.1016/j.ajhg.2011.05.007},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/pii/S000292971100200X}
}
@ARTICLE{Wright2009,
author = {Wright, John A. and Grant, Andrew J. and Hurd, Douglas and Harrison,
Marcus and Guccione, Edward J. and Kelly, David J. and Maskell, Duncan
J.},
title = {Metabolite and transcriptome analysis of Campylobacter jejuni in
vitro growth reveals a stationary-phase physiological switch},
journal = {Microbiology},
year = {2009},
volume = {155},
pages = {80--94},
number = {1},
month = jan,
abstract = {Campylobacter jejuni is a prevalent cause of food-borne diarrhoeal
illness in humans. Understanding of the physiological and metabolic
capabilities of the organism is limited. We report a detailed analysis
of the C. jejuni growth cycle in batch culture. Combined transcriptomic,
phenotypic and metabolic analysis demonstrates a highly dynamic stationary
phase', characterized by a peak in motility, numerous gene expression
changes and substrate switching, despite transcript changes that
indicate a metabolic downshift upon the onset of stationary phase.
Video tracking of bacterial motility identifies peak activity during
stationary phase. Amino acid analysis of culture supernatants shows
a preferential order of amino acid utilization. Proton NMR (1H-NMR)
highlights an acetate switch mechanism whereby bacteria change from
acetate excretion to acetate uptake, most probably in response to
depletion of other substrates. Acetate production requires pta (Cj0688)
and ackA (Cj0689), although the acs homologue (Cj1537c) is not required.
Insertion mutants in Cj0688 and Cj0689 maintain viability less well
during the stationary and decline phases of the growth cycle than
wild-type C. jejuni, suggesting that these genes, and the acetate
pathway, are important for survival.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/155/1/80}
}
@ARTICLE{Wright2008a,
author = {Wright, Mollie and Calcagno, Anna and Salcido, Crystal and Carlson,
Marisa and Ambudkar, Suresh and Varticovski, Lyuba},
title = {Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells
with cancer stem cell characteristics},
journal = {Breast Cancer Research},
year = {2008},
volume = {10},
pages = {R10},
number = {1},
note = {See related editorial by Wicha, http://breast-cancer-research.com/content/10/2/105},
abstract = {INTRODUCTION:Whether cancer stem cells occur in BRCA1-associated breast
cancer and contribute to therapeutic response is not known.METHODS:We
generated and characterized 16 cell lines from five distinct Brca1deficient
mouse mammary tumors with respect to their cancer stem cell characteristics.RESULTS:All
cell lines derived from one tumor included increased numbers of CD44+/CD24-
cells, which were previously identified as human breast cancer stem
cells. All cell lines derived from another mammary tumor exhibited
low levels of CD44+/CD24- cells, but they harbored 2% to 5.9% CD133+
cells, which were previously associated with cancer stem cells in
other human and murine tumors. When plated in the absence of attachment
without presorting, only those cell lines that were enriched in either
stem cell marker formed spheroids, which were further enriched in
cells expressing the respective cancer stem cell marker. In contrast,
cells sorted for CD44+/CD24- or CD133+ markers lost their stem cell
phenotype when cultured in monolayers. As few as 50 to 100 CD44+/CD24-
or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/severe
combined immunodeficient mice, whereas 50-fold to 100-fold higher
numbers of parental or stem cell depleted cells were required to
form few, slow-growing tumors. Expression of stem cell associated
genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased
in CD44+/CD24- and CD133+ cells. In addition, cells sorted for cancer
stem cell markers and spheroid-forming cells were significantly more
resistant to DNA-damaging drugs than were parental or stem cell depleted
populations, and they were sensitized to the drugs by the heat shock
protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin
hydrochloride).CONCLUSION:Brca1-deficient mouse mammary tumors harbor
heterogeneous cancer stem cell populations, and CD44+/CD24- cells
represent a population that correlates with human breast cancer stem
cells.},
doi = {10.1186/bcr1855},
issn = {1465-5411},
owner = {Meike Kuschel},
pubmedid = {18241344},
timestamp = {2010.04.07},
url = {http://breast-cancer-research.com/content/10/1/R10}
}
@ARTICLE{Wright2008b,
author = {Wright, Natasha and Samuelson, Lisa and Walkup, Maggie H. and Chandrasekaran,
Prakash and Gerber, David A.},
title = {Enrichment of a bipotent hepatic progenitor cell from naïve adult
liver tissue},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {366},
pages = {367--372},
number = {2},
month = feb,
abstract = {Background/Aim Recent interest in the liver stem cell field has led
to the identification and characterization of several hepatic progenitor
cell populations from fetal and adult tissues. We isolated a hepatic
progenitor cell from naïve adult liver and the current studies focus
on differentiation and growth.Results A Sca-1+ hepatic progenitor
cell was identified within the liver parenchyma. This cell expresses
numerous liver related genes and transcription found in the developing
and/or adult liver. It is located in the peri-portal region and expresses
markers associated with undifferentiated hepatic cell populations,
mature hepatocytes and biliary cells which distinguish it from the
Sca-1- fraction.Conclusion This hepatic progenitor cell from uninjured
liver has features of both hepatocytic and biliary populations and
demonstrates proliferative potential. Further studies will focus
on sca-HPC subsets and conditions that regulate differentiation towards
hepatic or biliary lineages.},
issn = {0006-291X},
keywords = {Hepatic, Liver, Progenitor cell, Stem cell, Bipotential, Differentiation},
url = {http://www.sciencedirect.com/science/article/B6WBK-4R8P455-2/2/614daf699b9b813e0fd89d9d88f24050}
}
@ARTICLE{Wu2007,
author = {Wu, Bin-Nan and Luykenaar, Kevin D. and Brayden, Joseph E. and Giles,
Wayne R. and Corteling, Randolph L. and Wiehler, William B. and Welsh,
Donald G.},
title = {Hyposmotic challenge inhibits inward rectifying K+ channels in cerebral
arterial smooth muscle cells},
journal = {Am J Physiol Heart Circ Physiol},
year = {2007},
volume = {292},
pages = {H1085--1094},
number = {2},
month = feb,
abstract = {This study sought to define whether inward rectifying K+ (KIR) channels
were modulated by vasoactive stimuli known to depolarize and constrict
intact cerebral arteries. Using pressure myography and patch-clamp
electrophysiology, initial experiments revealed a Ba2+-sensitive
KIR current in cerebral arterial smooth muscle cells that was active
over a physiological range of membrane potentials and whose inhibition
led to arterial depolarization and constriction. Real-time PCR, Western
blot, and immunohistochemical analyses established the expression
of both KIR2.1 and KIR2.2 in cerebral arterial smooth muscle cells.
Vasoconstrictor agonists known to depolarize and constrict rat cerebral
arteries, including uridine triphosphate, U46619 , and 5-HT, had
no discernable effect on whole cell KIR activity. Control experiments
confirmed that vasoconstrictor agonists could inhibit the voltage-dependent
delayed rectifier K+ (KDR) current. In contrast to these observations,
a hyposmotic challenge that activates mechanosensitive ion channels
elicited a rapid and sustained inhibition of the KIR but not the
KDR current. The hyposmotic-induced inhibition of KIR was 1) mimicked
by phorbol-12-myristate-13-acetate, a PKC agonist; and 2) inhibited
by calphostin C, a PKC inhibitor. These findings suggest that, by
modulating PKC, mechanical stimuli can regulate KIR activity and
consequently the electrical and mechanical state of intact cerebral
arteries. We propose that the mechanoregulation of KIR channels plays
a role in the development of myogenic tone.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/292/2/H1085}
}
@ARTICLE{Wu2010c,
author = {Wu, Colleen and Nik-Amini, Saied and Nadesan, Puviindran and Stanford,
William L. and Alman, Benjamin A.},
title = {Aggressive Fibromatosis (Desmoid Tumor) Is Derived from Mesenchymal
Progenitor Cells},
journal = {Cancer Res.},
year = {2010},
volume = {70},
pages = {7690--7698},
number = {19},
month = oct,
abstract = {The cellular origins from which most tumors arise are poorly defined,
especially in mesenchymal neoplasms. Aggressive fibromatosis, also
known as desmoid tumor, is a locally invasive soft tissue tumor that
has mesenchymal characteristics. We found that aggressive fibromatosis
tumors express genes and cell surface markers characteristic of mesenchymal
stem cells (MSC). In mice that are genetically predisposed to develop
aggressive fibromatosis tumors (Apcwt/1638N), we found that the number
of tumors formed was proportional to the number of MSCs present.
Sca-1-/- mice, which develop fewer MSCs, were crossed with Apcwt/1638N
mice. Doubly mutant mice deficient in Sca-1 developed substantially
fewer aggressive fibromatosis tumors than wild-type (WT) littermates,
but Sca-1 deficiency had no effect on the formation of epithelial-derived
intestinal polyps. MSCs isolated from Apcwt/1638N mice (or mice expressing
a stabilized form of {beta}-catenin) induced aberrant cellular growth
reminiscent of aggressive fibromatosis tumors after engraftment to
immunocompromised mice, but WT cells and mature fibroblasts from
the same animals did not. Taken together, our findings indicate that
aggressive fibromatosis is derived from MSCs, and that {beta}-catenin
supports tumorigenesis by maintaining mesenchymal progenitor cells
in a less differentiated state. Protecting this progenitor cell population
might prevent tumor formation in patients harboring a germline APC
mutation, where fibromatosis is currently the leading cause of mortality.
Cancer Res; 70(19); 7690-8. (C)2010 AACR.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/70/19/7690}
}
@ARTICLE{Wu2011g,
author = {Wu, Chang-Chieh and Tsai, Fu-Ming and Shyu, Rong-Yaun and Tsai, Ya-Ming
and Wang, Chun-Hua and Jiang, Shun-Yuan},
title = {G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene
1-induced growth suppression of human colon cancer cells},
journal = {BMC Cancer},
year = {2011},
volume = {11},
pages = {175},
number = {1},
abstract = {BACKGROUND:Tazarotene-induced gene 1 (TIG1) is a retinoid-inducible
type II tumour suppressor gene. The B isoform of TIG1 (TIG1B) inhibits
growth and invasion of cancer cells. Expression of TIG1B is frequently
downregulated in various cancer tissues; however, the expression
and activities of the TIG1A isoform are yet to be reported. Therefore,
this study investigated the effects of the TIG1A and TIG1B isoforms
on cell growth and gene expression profiles using colon cancer cells.METHODS:TIG1A
and TIG1B stable clones derived from HCT116 and SW620 colon cancer
cells were established using the GeneSwitch system; TIG1 isoform
expression was induced by mifepristone treatment. Cell growth was
assessed using the WST-1 cell proliferation and colony formation
assays. RNA interference was used to examine the TIG1 mediating changes
in cell growth. Gene expression profiles were determined using microarray
and validated using real-time polymerase chain reaction, and Western
blot analyses. RESULTS:Both TIG1 isoforms were expressed at high
levels in normal prostate and colon tissues and were downregulated
in colon cancer cell lines. Both TIG1 isoforms significantly inhibited
the growth of transiently transfected HCT116 cells and stably expressing
TIG1A and TIG1B HCT116 and SW620 cells. Expression of 129 and 55
genes was altered upon induction of TIG1A and TIG1B expression, respectively,
in stably expressing HCT116 cells. Of the genes analysed, 23 and
6 genes were upregulated and downregulated, respectively, in both
TIG1A and TIG1B expressing cells. Upregulation of the G protein-coupled
receptor kinase 5 (GRK5) was confirmed using real-time polymerase
chain reaction and Western blot analyses in both TIG1 stable cell
lines. Silencing of TIG1A or GRK5 expression significantly decreased
TIG1A-mediated cell growth suppression. CONCLUSIONS:Expression of
both TIG1 isoforms was observed in normal prostate and colon tissues
and was downregulated in colon cancer cell lines. Both TIG1 isoforms
suppressed cell growth and stimulated GRK5 expression in HCT116 and
SW620 cells. Knockdown of GRK5 expression alleviated TIG1A-induced
growth suppression of HCT116 cells, suggesting that GRK5 mediates
cell growth suppression by TIG1A. Thus, TIG1 may participate in the
downregulation of G protein-coupled signaling by upregulating GRK5
expression.},
doi = {10.1186/1471-2407-11-175},
issn = {1471-2407},
pubmedid = {21575264},
url = {http://www.biomedcentral.com/1471-2407/11/175}
}
@ARTICLE{Wu2005,
author = {Wu, Chung-Pu and Calcagno, Anna Maria and Hladky, Stephen B. and
Ambudkar, Suresh V. and Barrand, Margery A.},
title = {Modulatory effects of plant phenols on human multidrug-resistance
proteins 1, 4 and 5 (ABCC1, 4 and 5)},
journal = {FEBS Journal},
year = {2005},
volume = {272},
pages = {4725--4740},
number = {18},
abstract = {Plant flavonoids are polyphenolic compounds, commonly found in vegetables,
fruits and many food sources that form a significant portion of our
diet. These compounds have been shown to interact with several ATP-binding
cassette transporters that are linked with anticancer and antiviral
drug resistance and, as such, may be beneficial in modulating drug
resistance. This study investigates the interactions of six common
polyphenols; quercetin, silymarin, resveratrol, naringenin, daidzein
and hesperetin with the multidrug-resistance-associated proteins,
MRP1, MRP4 and MRP5. At nontoxic concentrations, several of the polyphenols
were able to modulate MRP1-, MRP4- and MRP5-mediated drug resistance,
though to varying extents. The polyphenols also reversed resistance
to NSC251820, a compound that appears to be a good substrate for
MRP4, as predicted by data-mining studies. Furthermore, most of the
polyphenols showed direct inhibition of MRP1-mediated [3H]dinitrophenyl S-glutathione
and MRP4-mediated [3H]cGMP transport in inside-out vesicles prepared
from human erythrocytes. Also, both quercetin and silymarin were
found to inhibit MRP1-, MRP4- and MRP5-mediated transport from intact
cells with high affinity. They also had significant effects on the
ATPase activity of MRP1 and MRP4 without having any effect on [32P]8-azidoATP[αP]
binding to these proteins. This suggests that these flavonoids most
likely interact at the transporter's substrate-binding sites. Collectively,
these results suggest that dietary flavonoids such as quercetin and
silymarin can modulate transport activities of MRP1, -4 and -5. Such
interactions could influence bioavailability of anticancer and antiviral
drugs in vivo and thus, should be considered for increasing efficacy
in drug therapies.},
issn = {1742-4658},
keywords = {ABC transporters, drug resistance, multidrug-resistant proteins 1,
4 and 5, plant polyphenols, red blood cells},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1742-4658.2005.04888.x}
}
@ARTICLE{Wu2011c,
author = {Wu, Da-Qiang and Ye, Jing and Ou, Hong-Yu and Wei, Xue and Huang,
Xianqing and He, Ya-Wen and Xu, Yuquan},
title = {Genomic analysis and temperature-dependent transcriptome profiles
of the rhizosphere originating strain Pseudomonas aeruginosa M18},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {438},
number = {1},
abstract = {BACKGROUND:Our previously published reports have described an effective
biocontrol agent named Pseudomonas sp. M18 as its 16S rDNA sequence
and several regulator genes share homologous sequences with those
of P. aeruginosa, but there are several unusual phenotypic features.
This study aims to explore its strain specific genomic features and
gene expression patterns at different temperatures.RESULTS:The complete
M18 genome is composed of a single chromosome of 6,327,754 base pairs
containing 5684 open reading frames. Seven genomic islands, including
two novel prophages and five specific non-phage islands were identified
besides the conserved P. aeruginosa core genome. Each prophage contains
a putative chitinase coding gene, and the prophage II contains a
capB gene encoding a putative cold stress protein. The non-phage
genomic islands contain genes responsible for pyoluteorin biosynthesis,
environmental substance degradation and type I and III restriction-modification
systems. Compared with other P. aeruginosa strains, the fewest number
(3) of insertion sequences and the most number (3) of clustered regularly
interspaced short palindromic repeats in M18 genome may contribute
to the relative genome stability. Although the M18 genome is most
closely related to that of P. aeruginosa strain LESB58, the strain
M18 is more susceptible to several antimicrobial agents and easier
to be erased in a mouse acute lung infection model than the strain
LESB58. The whole M18 transcriptomic analysis indicated that 10.6%
of the expressed genes are temperature-dependent, with 22 genes up-regulated
at 28degreesC in three non-phage genomic islands and one prophage
but none at 37degreesC.CONCLUSIONS:The P. aeruginosa strain M18 has
evolved its specific genomic structures and temperature dependent
expression patterns to meet the requirement of its fitness and competitiveness
under selective pressures imposed on the strain in rhizosphere niche.},
doi = {10.1186/1471-2164-12-438},
issn = {1471-2164},
pubmedid = {21884571},
url = {http://www.biomedcentral.com/1471-2164/12/438}
}
@ARTICLE{Wu2011a,
author = {Wu, Feng and Guo, Natalie Jia and Tian, Hongying and Marohn, Michael
and Gearhart, Susan and Bayless, Theodore M. and Brant, Steven R.
and Kwon, John H.},
title = {Peripheral blood MicroRNAs distinguish active ulcerative colitis
and Crohn's disease},
journal = {Inflammatory Bowel Diseases},
year = {2011},
volume = {17},
pages = {241--250},
number = {1},
abstract = {Abstract Background:Crohn's disease (CD) and ulcerative colitis (UC)
result from pathophysiologically distinct dysregulated immune responses,
as evidenced by the preponderance of differing immune cell mediators
and circulating cytokine expression profiles. MicroRNAs (miRNAs)
are small, noncoding RNAs that act as negative regulators of gene
expression and have an increasingly recognized role in immune regulation.
We hypothesized that differences in circulating immune cells in CD
and UC patients are reflected by altered miRNA expression and that
miRNA expression patterns can distinguish CD and UC from normal healthy
individuals.Methods:Peripheral blood was obtained from patients with
active CD, inactive CD, active UC, inactive UC, and normal healthy
adults. Total RNA was isolated and miRNA expression assessed using
miRNA microarray and validated by mature miRNA quantitative reverse-transcription
polymerase chain reaction.Results:Five miRNAs were significantly
increased and two miRNAs (149* and miRplus-F1065) were significantly
decreased in the blood of active CD patients as compared to healthy
controls. Twelve miRNAs were significantly increased and miRNA-505*
was significantly decreased in the blood of active UC patients as
compared to healthy controls. Ten miRNAs were significantly increased
and one miRNA was significantly decreased in the blood of active
UC patients as compared to active CD patients.Conclusions:Peripheral
blood miRNAs can be used to distinguish active CD and UC from healthy
controls. The data support the evidence that CD and UC are associated
with different circulating immune cells types and that the differential
expression of peripheral blood miRNAs may form the basis of future
diagnostic tests for inflammatory bowel disease. (Inflamm Bowel Dis
2011;)},
doi = {10.1002/ibd.21450},
issn = {1536-4844},
keywords = {microRNA, Crohn's disease, ulcerative colitis, peripheral blood},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.21450}
}
@ARTICLE{Wu2006,
author = {Wu, Hong and Zheng, Xiaohong and Araki, Yoshio and Sahara, Hiroshi
and Takagi, Hiroshi and Shimoi, Hitoshi},
title = {Global Gene Expression Analysis of Yeast Cells during Sake Brewing},
journal = {Appl. Envir. Microbiol.},
year = {2006},
volume = {72},
pages = {7353--7358},
number = {11},
month = nov,
abstract = {During the brewing of Japanese sake, Saccharomyces cerevisiae cells
produce a high concentration of ethanol compared with other ethanol
fermentation methods. We analyzed the gene expression profiles of
yeast cells during sake brewing using DNA microarray analysis. This
analysis revealed some characteristics of yeast gene expression during
sake brewing and provided a scaffold for a molecular level understanding
of the sake brewing process.},
url = {http://aem.asm.org/cgi/content/abstract/72/11/7353}
}
@ARTICLE{Wu2007a,
author = {Wu, Henry D. and Maurer, Mathew S. and Friedman, Richard A. and Marboe,
Charles C. and Ruiz-Vazquez, Elena M. and Ramakrishnan, Rajasekhar
and Schwartz, Allan and Tilson, M. David and Stewart, Allan S. and
Winchester, Robert},
title = {The Lymphocytic Infiltration in Calcific Aortic Stenosis Predominantly
Consists of Clonally Expanded T Cells},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {5329--5339},
number = {8},
month = apr,
abstract = {Valve lesions in degenerative calcific aortic stenosis (CAS), a disorder
affecting 3% of those older than 75 years, are infiltrated by T lymphocytes.
We sought to determine whether the {alpha}[beta] TCR repertoire of
these valve-infiltrating lymphocytes exhibited features either of
a polyclonal nonselective response to inflammation or contained expanded
clones suggesting a more specific immune process. TCR [beta]-chain
CDR3-length distribution analysis using PCR primers specific for
23 V[beta] families performed in eight individuals with CAS affecting
tri- or bileaflet aortic valves revealed considerable oligoclonal
T cell expansion. In five cases, [beta]-chain nucleotide sequencing
in five selected V[beta] families showed that an average of 92% of
the valve-infiltrating T cell repertoire consisted of expanded T
cell clones, differing markedly in composition from the relatively
more polyclonal peripheral CD8 or CD4 T cell subsets found even in
this elderly population. Twenty-four of the valve-infiltrating T
cell clones also had the same clone identified in blood, some of
which were highly expanded. Interestingly, 22 of these 24 shared
clones were CD8 in lineage (p = 1.5 x 10-12), suggesting a possible
relationship to the expanded CD8+CD28- T cell clones frequently present
in the elderly. Additionally, the sequences of several TCR [beta]-chain
CDR3 regions were homologous to TCR [beta]-chains identified previously
in allograft arteriosclerosis. We infer that these findings are inconsistent
with a nonselective secondary response of T cells to inflammation
and instead suggest that clonally expanded {alpha}[beta] T cells
are implicated in mediating a component of the valvular injury responsible
for CAS.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/8/5329}
}
@ARTICLE{Wu2009,
author = {Wu, Hsuan-Chen and Shi, Xiao-Wen and Tsao, Chen-Yu and Lewandowski,
Angela T. and Fernandes, Rohan and Hung, Chi-Wei and DeShong, Philip
and Kobatake, Eiry and Valdes, James J. and Payne, Gregory F. and
Bentley, William E.},
title = {Biofabrication of antibodies and antigens via IgG-binding domain
engineered with activatable pentatyrosine pro-tag},
journal = {Biotechnol. Bioeng.},
year = {2009},
volume = {103},
pages = {231--240},
number = {2},
abstract = {Abstract 10.1002/bit.22238.abs We report the assembly of seven different
antibodies (and two antigens) into functional supramolecular structures
that are specifically designed to facilitate integration into devices
using entirely biologically based bottom-up fabrication. This is
enabled by the creation of an engineered IgG-binding domain (HG3T)
with an N-terminal hexahistidine tag that facilitates purification
and a C-terminal enzyme-activatable pentatyrosine “pro-tag� that
facilitates covalent coupling to the pH stimuli-responsive polysaccharide,
chitosan. Because we confer pH-stimuli responsiveness to the IgG-binding
domain, it can be electrodeposited or otherwise assembled into many
configurations. Importantly, we demonstrate the loading of both HG3T
and antibodies can be achieved in a linear fashion so that quantitative
assessment of antibodies and antigens is feasible. Our demonstration
formats include: conventional multiwell plates, micropatterned electrodes,
and fiber networks. We believe biologically based fabrication (i.e.,
biofabrication) provides bottom-up hierarchical assembly of a variety
of nanoscale components for applications that range from point-of-care
diagnostics to smart fabrics. Biotechnol. Bioeng. 2009;103: 231–240.
© 2008 Wiley Periodicals, Inc.},
issn = {1097-0290},
keywords = {protein G, chitosan, biofabrication, antibody, tyrosine tag},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/bit.22238}
}
@ARTICLE{Wu2011d,
author = {Wu, Jing and Dwyer, Dominic and Dyer, Wayne and Yang, Yee and Wang,
Bin and Saksena, Nitin},
title = {Genome-wide analysis of primary CD4+ and CD8+ T cell transcriptomes
shows evidence for a network of enriched pathways associated with
HIV disease},
journal = {Retrovirology},
year = {2011},
volume = {8},
pages = {18},
number = {1},
abstract = {BACKGROUND:HIV preferentially infects CD4+ T cells, and the functional
impairment and numerical decline of CD4+ and CD8+ T cells characterize
HIV disease. The numerical decline of CD4+ and CD8+ T cells affects
the optimal ratio between the two cell types necessary for immune
regulation. Therefore, this work aimed to define the genomic basis
of HIV interactions with the cellular transcriptome of both CD4+
and CD8+ T cells.RESULTS:Genome-wide transcriptomes of primary CD4+
and CD8+ T cells from HIV+ patients were analyzed at different stages
of HIV disease using Illumina microarray. For each cell subset, pairwise
comparisons were performed and differentially expressed (DE) genes
were identified (fold change >2 and B-statistic >0) followed by quantitative
PCR validation. Gene ontology (GO) analysis of DE genes revealed
enriched categories of complement activation, actin filament, proteasome
core and proton-transporting ATPase complex. By gene set enrichment
analysis (GSEA), a network of enriched pathways functionally connected
by mitochondria was identified in both T cell subsets as a transcriptional
signature of HIV disease progression. These pathways ranged from
metabolism and energy production (TCA cycle and OXPHOS) to mitochondria
meditated cell apoptosis and cell cycle dysregulation. The most unique
and significant feature of our work was that the non-progressing
status in HIV+ long-term non-progressors was associated with MAPK,
WNT, and AKT pathways contributing to cell survival and anti-viral
responses.CONCLUSIONS:These data offer new comparative insights into
HIV disease progression from the aspect of HIV-host interactions
at the transcriptomic level, which will facilitate the understanding
of the genetic basis of transcriptomic interaction of HIV in vivo
and how HIV subverts the human gene machinery at the individual cell
type level.},
doi = {10.1186/1742-4690-8-18},
issn = {1742-4690},
pubmedid = {21410942},
url = {http://www.retrovirology.com/content/8/1/18}
}
@ARTICLE{Wu2009a,
author = {Wu, Jie and Lin, Xinghua and Xie, Hua},
title = {Regulation of Hemin Binding Proteins by a Novel Transcriptional Activator
in Porphyromonas gingivalis},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {115--122},
number = {1},
month = jan,
abstract = {One of the features of the periodontal pathogen Porphyromonas gingivalis
is the presence of complex iron acquisition systems that include
an hmuYRSTUV locus. HmuY and HmuR are hemin binding proteins required
for P. gingivalis growth. Previous studies have demonstrated that
expression of the hmu locus is regulated in response to environmental
changes, such as growth phases. However, the mechanisms involved
in hmu gene regulation are poorly understood. Here we report that
a novel transcriptional activator, PG1237, is required for the expression
of humY and humR, but not other iron acquisition-related genes, such
as fetB and tlr, which also encode hemin binding proteins. Real-time
reverse transcription-PCR analysis revealed that a mutation in the
pg1237 gene decreased expression of hmuY and hmuR 149- and 25-fold,
respectively, compared to that observed in the wild-type strain.
In addition, differential expression of hmuY, hmuR, and the pg1237
gene was found to be quorum-sensing dependent, such that higher expression
levels of these genes were observed when P. gingivalis was grown
at a lower cell density, such as that seen during the early exponential
growth phase. This work demonstrates the involvement of a novel transcriptional
activator, PG1237, in expression of the hmu operon in a cell density-dependent
fashion.},
url = {http://jb.asm.org/cgi/content/abstract/191/1/115}
}
@ARTICLE{Wu2008,
author = {Wu, Jie and Lin, Xinghua and Xie, Hua},
title = {OxyR is involved in coordinate regulation of expression of fimA and
sod genes in Porphyromonas gingivalis},
journal = {FEMS Microbiology Letters},
year = {2008},
volume = {282},
pages = {188--195},
number = {2},
abstract = {Abstract Survival of Porphyromonas gingivalis in the constantly changing
oral environment depends on its ability to alter gene expression.
We demonstrate here that P. gingivalis activates superoxide dismutase
expression in response to oxidative stress and represses expression
of FimA, a subunit of major fimbriae. Coordinated expression of fimA
and sod is regulated by the redox-sensing transcription factor OxyR.
Mutations in the oxyR gene result in a decreased expression of sod
and in an elevated expression of fimA. In addition, we provide evidence
that regulation of expression of fimA and sod by OxyR is mediated
by direct interaction of OxyR and the promoters of these two genes.
These results suggest that OxyR plays an important role in regulation
of expression of virulence genes in P. gingivalis.},
issn = {1574-6968},
keywords = {fimbriae, SOD, OxyR},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2008.01116.x}
}
@ARTICLE{Wu2007b,
author = {Wu, Jie and Lin, Xinghua and Xie, Hua},
title = {Porphyromonas gingivalis short fimbriae are regulated by a FimS/FimR
two-component system},
journal = {FEMS Microbiology Letters},
year = {2007},
volume = {271},
pages = {214--221},
number = {2},
abstract = {Abstract Porphyromonas gingivalis possesses two distinct fimbriae.
The long (FimA) fimbriae have been extensively studied. Expression
of the fimA gene is tightly controlled by a two-component system
(FimS/FimR) through a cascade regulation. The short (Mfa1) fimbriae
are less understood. The authors have recently demonstrated that
both fimbriae are required for formation of P. gingivalis biofilms.
Here, the novel finding that FimR, a member of the two-component
regulatory system, is a transcriptional activator of the mfa1 gene
is promoted. Unlike the regulatory mechanism of FimA by FimR, this
regulation of the mfa1 gene is accomplished by FimR directly binding
to the promoter region of mfa1.},
issn = {1574-6968},
keywords = {gene regulation, Porphyromonas gingivalis, two-component system},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1574-6968.2007.00722.x}
}
@ARTICLE{Wu2012,
author = {Jing Wu and Chanyi Lu and Ni Diao and Shu Zhang and Sen Wang and
Feifei Wang and Yan Gao and Jiazhen Chen and Lingyun Shao and Jingning
Lu and Xuelian Zhang and Xinhua Weng and Honghai Wang and Wenhong
Zhang and Yuxian Huang},
title = {Analysis of microRNA expression profiling identifies miR-155 and
miR-155* as potential diagnostic markers for active tuberculosis:
a preliminary study},
journal = {Human Immunology},
year = {2012},
volume = {73},
pages = {31 - 37},
number = {1},
abstract = {To explore biologic behaviors and disease relevance of microRNAs (miRNAs)
in the development of active tuberculosis (ATB), we investigated
the expression profile of Mycobacterium tuberculosis (MTB) purified
protein derivative (PPD)–induced miRNAs to determine the specific
miRNAs involved in the pathogenesis of ATB. The expression profile
of miRNA under PPD challenge was first measured using microarray
analysis in peripheral blood mononuclear cells isolated from ATB
patients and healthy controls (HC). The remarkably reactive miRNAs
were then validated in a larger cohort by quantitative real-time
polymerase chain reaction (qRT-PCR). The receiver operating characteristic
(ROC) curve was plotted to evaluate the diagnostic value of the determined
PPD-responsive miRNAs. The potential targets for those miRNAs were
also predicted by computational programs. Fourteen of 866 human miRNAs
exhibited at least 1.8-fold difference in the ratio of expression
level before and after stimulation with PPD between the ATB and HC
groups. The qRT-PCR study validated the findings from microarray-based
screening, in which miR-155 exhibited a fold change of 1.4 in the
HC group and 3.7 in the ATB group upon PPD stimulation (p < 0.0001);
miR-155* exhibited a fold change of 1.9 in the HC and 4.6 in the
ATB group (p < 0.005). In ROC plots, the area under the curve
was 0.8972 for miR-155 and 0.7945 for miR-155*. The background expression
of these 2 microRNAs exhibited no differences between the ATB and
HC groups. miR-155 and miR-155* exhibited characteristic expression
by TB-specific antigen, suggesting that they can be potential diagnostic
markers under the challenge of specific MTB antigens.},
doi = {10.1016/j.humimm.2011.10.003},
issn = {0198-8859},
keywords = {Tuberculosis},
url = {http://www.sciencedirect.com/science/article/pii/S0198885911005490}
}
@ARTICLE{Wu2008a,
author = {Wu, Jing Qin and Dwyer, Dominic E. and Dyer, Wayne B. and Yang, Yee
Hwa and Wang, Bin and Saksena, Nitin K.},
title = {Transcriptional profiles in CD8+ T cells from HIV+ progressors on
HAART are characterized by coordinated up-regulation of oxidative
phosphorylation enzymes and interferon responses},
journal = {Virology},
year = {2008},
volume = {380},
pages = {124--135},
number = {1},
month = oct,
abstract = {The functional impairment and numerical decline of CD8+ T cells during
HIV infection has a profound effect on disease progression, but only
limited microarray studies have used CD8+ T cells. To understand
the interactions of HIV and host CD8+ T cells at different disease
status, we used the Illumina Human-6 BeadChips to evaluate the transcriptional
profile (> 48,000 transcripts) in primary CD8+ T cells from HIV+
therapy-naive non-progressors and therapy-experienced progressors.
68 differentially expressed genes were identified, of which 6 have
been reported in HIV context, while others are associated with biological
functions relevant to HIV pathogenesis. By GSEA, the coordinated
up-regulation of oxidative phosphorylation enzymes and interferon
responses were detected as fingerprints in HIV progressors on HAART,
whereas LTNP displayed a transcriptional signature of coordinated
up-regulation of components of MAPK and cytotoxicty pathways. These
results will provide biological insights into natural control of
HIV versus HIV control under HAART.},
issn = {0042-6822},
keywords = {HAART, highly active antiretroviral therapy, NEG, HIV sero-negative
individuals, VIR, viremic patients, LTNP, long-term non-progressor,
GO, gene ontology, GSEA, gene set enrichment analysis, FDR, false
discovery rate, OXPHOS, oxidative phosphorylation, NRTI, nucleoside
reverse transcriptase inhibitors, AZT, zidovudine, ES, enrichment
score, NES, normalized enrichment score, ISG, interferon stimulated
genes, CTL, cytotoxic T lymphocyte, Microarray, HIV, CD8+, HAART,
Gene expression, Interferon, Mitochondria, Cytotoxicity},
url = {http://www.sciencedirect.com/science/article/B6WXR-4T5S49P-1/2/5eb62413d684d399a65ea728aedc9f02}
}
@ARTICLE{Wu2008b,
author = {Wu, Jing Qin and Wang, Bin and Saksena, Nitin K.},
title = {Transitory Viremic Surges in a Human Immunodeficiency Virus-Positive
Elite Controller Can Shift the Cellular Transcriptome Profile: a
Word of Caution for Microarray Studies},
journal = {J. Virol.},
year = {2008},
volume = {82},
pages = {10326--10327},
number = {20},
month = oct,
url = {http://jvi.asm.org}
}
@ARTICLE{Wu2011h,
author = {Wu, Jong-C. and Hseu, You-Cheng and Tsai, Jui-Shan and Chen, Lei-Chin
and Chye, Soi M. and Chen, Chin-H. and Ching Chen, Ssu},
title = {Fenthion and terbufos induce DNA damage, the expression of tumor-related
genes, and apoptosis in HEPG2 cells},
journal = {Environmental and Molecular Mutagenesis},
year = {2011},
volume = {52},
pages = {529--537},
number = {7},
abstract = {This study investigates the effects of fenthion and terbufos, two
organophosphorous pesticides, on DNA damage, tumor-related gene expression,
and apoptosis in HepG2 cells. We found that exposure to concentrations
ranging from 50 to 200 μM of fenthion and terbufos for 2 hr caused
significant death in HepG2 cells. Both compounds induced DNA damage
in a concentration-dependent manner as measured using the alkaline
comet assay. Tumor-related genes (jun, myc, and fos) and apoptosis-related
genes (socs3, tnfaip3, ppp1r15a, and nr4a1) were up-regulated by
both compounds. Finally, both compounds induced apoptosis. The results
demonstrate that both terbufos and fenthion induce DNA damage and
should be considered potentially hazardous to humans. Environ. Mol.
Mutagen., 2011. © 2011 Wiley-Liss, Inc.},
doi = {10.1002/em.20652},
issn = {1098-2280},
keywords = {fenthion, terbufos, comet assay, apoptosis, tumor-related genes},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/em.20652}
}
@ARTICLE{Wu2010a,
author = {Wu, Jian-Min and Skill, Nicholas J. and Maluccio, Mary A.},
title = {Evidence of aberrant lipid metabolism in hepatitis C and hepatocellular
carcinoma},
journal = {HPB},
year = {2010},
volume = {12},
pages = {625--636},
number = {9},
abstract = {Abstract Objectives:  Lipids are linked to many pathological processes
including hepatic steatosis and liver malignancy. This study aimed
to explore lipid metabolism in hepatitis C virus (HCV) and HCV-related
hepatocellular carcinoma (HCC). Methods:  Serum lipids were measured
in normal, HCV and HCV-HCC patients. Whole-genome microarray was
performed to identify potential signature genes involved in lipid
metabolism characterizing normal vs. HCV vs. HCV-HCC conditions.
Results:  Serum cholesterol was significantly reduced in HCV and
HCV-HCC patients compared with normal controls, whereas there was
no difference in glucose and triglycerides. Microarray analysis identified
224 probe sets with known functional roles in lipid metabolism (anova,
1.5-fold, P≤ 0.001). Gene-mediated fatty acid (FA) de novo synthesis
and uptake were upregulated in HCV and this upregulation was further
enhanced in HCC. Genes involved in FA oxidation were downregulated
in both the HCV and HCC groups. The abnormality of cholesterol metabolism
in HCV was associated with downregulation of genes involved in cholesterol
biosynthesis, absorption and transportation and bile acid synthesis;
this abnormality was further intensified in HCC. Conclusions: 
Our data support the notion that HCV-related lipid metabolic abnormalities
may contribute to hepatic steatosis and the development of cancer.
Identification of these aberrations would stratify patients and improve
treatment algorithms.},
issn = {1477-2574},
keywords = {hepatitis C virus (HCV), lipid metabolism, hepatic steatosis, hepatocellular
carcinoma (HCC)},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1477-2574.2010.00207.x}
}
@ARTICLE{Wu2009b,
author = {Wu, Kaijin and Joffre, Corrine and Li, Xiaodong and MacVeigh-Aloni,
Michelle and Hom, Melinda and Hwang, Juliana and Ding, Chuanqing
and Gregoire, Stephane and Bretillon, Lionel and Zhong, Jiang F.
and Hamm-Alvarez, Sarah F.},
title = {Altered expression of genes functioning in lipid homeostasis is associated
with lipid deposition in NOD mouse lacrimal gland},
journal = {Experimental Eye Research},
year = {2009},
volume = {89},
pages = {319--332},
number = {3},
month = sep,
abstract = {Functional atrophy and accompanying lymphocytic infiltration and destruction
of the lacrimal gland (LG) are characteristics of Sjögren's Syndrome
(SjS). The male NOD mouse is an experimental model for the autoimmune
exocrinopathy that develops in the LG of SjS patients. Acinar cells
in LG of male NOD mice aged 3-4 months were previously shown to accumulate
lipid droplets. In the current study, analysis of lipid components
revealed that the accumulated lipids were mostly cholesteryl esters
(CE). Gene expression microarray analysis followed by real-time RT-PCR
revealed alterations in the expression of several genes involved
in lipid homeostasis in LG of 12-week-old male NOD mice relative
to matched BALB/c controls. A series of upregulated genes including
apolipoprotein E, apolipoprotein F, hepatic lipase, phosphomevalonate
kinase, ATP-binding cassette D1 and ATP-binding cassette G1 were
identified. Comparison of liver mRNAs to LG mRNAs in BALB/c and NOD
mice revealed that the differential expressions were LG-specific.
Gene expression profiles were also characterized in LGs of female
mice, younger mice and immune-incompetent NOD SCID mice. Investigation
of the cellular distribution of Apo-E and Apo-F proteins suggested
that these proteins normally coordinate to mediate lipid efflux from
the acinar cells but that dysfunction of these processes due to missorting
of Apo-F may contribute to CE deposition. Finally, the initiation
and extent of lipid deposition were correlated with lymphocytic infiltration
in the LG of male NOD mice. We propose that impaired lipid efflux
contributes to lipid deposition, an event that may contribute to
the development and/or progression of dacryoadenitis in the male
NOD mouse.},
issn = {0014-4835},
keywords = {NOD mouse, lacrimal gland, Sjögren's syndrome, microarray, lipid,
apolipoprotein F, apolipoprotein E},
url = {http://www.sciencedirect.com/science/article/B6WFD-4W04KN4-1/2/8b3a385cd00b442b67fbace2aaa511a8}
}
@ARTICLE{Wu2011,
author = {Wu, Ming-Tsang and Lee, Tzu-Chi and Wu, I-Chen and Su, Hung-Ju and
Huang, Jie-Len and Peng, Chiung-Yu and Wang, Weihsin and Chou, Ting-Yu
and Lin, Ming-Yen and Lin, Wen-Yi and Huang, Chia-Tsuan and Pan,
Chih-Hong and Ho, Chi-Kung},
title = {Whole Genome Expression in Peripheral-Blood Samples of Workers Professionally
Exposed to Polycyclic Aromatic Hydrocarbons},
journal = {Chemical Research in Toxicology},
year = {2011},
volume = {24},
pages = {1636-1643},
number = {10},
abstract = { This study aims to examine global gene expression profiles before
and after the work-shift among coke-oven workers (COWs). COWs work
six consecutive days and then take two days off. Two blood and urine
samples in each worker were collected before starting to work after
two days off and end-of-shift in the sixth day of work in 2009. Altered
gene expressions (ratio of gene expression levels between end-of-shift
and preshift work) were performed by a Human OneArray expression
system which probes ∼30,000-transcription expression profiling
of human genes. Sixteen workers, all men, were enrolled in this study.
Median urinary 1-hydroxypyrene (1OHP) levels (μmol/mol creatinine)
in end-of-shift work were significantly higher than those in preshift
work (2.58 vs 0.29, p = 0.0002). Among the 20,341 genes which passed
experimental quality control, 26 gene expression changes, 7 positive
and 19 negative, were highly correlated with across-the-shift urinary
1OHP levels (end-of-shift−preshift 1OHP) (p-value <0.001). The
high and low exposure groups of across-the-shift urinary 1OHP levels
dichotomized in ∼2.00 μmol/mol creatinine were able to be distinguished
by these 26 genes. Some of them are known to be involved in apoptosis,
chromosome stability/DNA repair, cell cycle control/tumor suppressor,
cell adhesion, development/spermatogenesis, immune function, and
neuronal cell function. These findings in COWs will be an ideal model
to study the relationship of PAH exposure with acute changes of gene
expressions. },
doi = {10.1021/tx200181q},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/tx200181q},
url = {http://pubs.acs.org/doi/abs/10.1021/tx200181q}
}
@ARTICLE{Wu2009c,
author = {Wu, Pu and Jiang, Cecilia and Shen, Qian and Hu, Yinghe},
title = {Systematic gene expression profile of hypothalamus in calorie-restricted
mice implicates the involvement of mTOR signaling in neuroprotective
activity},
journal = {Mechanisms of Ageing and Development},
year = {2009},
volume = {130},
pages = {602--610},
number = {9},
month = sep,
abstract = {Calorie restriction (CR) delays aging and onset of age-related diseases
in a variety of organisms from yeast to mammals. However, the molecular
mechanism underlying the CR effect remains to be elucidated. It is
well known that the hypothalamus is an important component of the
brain neuroendocrine system for the regulation of the aging process.
In this report, we have systematically examined the gene expression
profiles of hypothalami from 5-, 12-, 19- and 24-month-old mice fed
ad libitum or subjected to CR since weaning. Our results demonstrated
that CR significantly altered the expression level of 490 genes in
an age-dependent manner, with the greatest impact at middle age.
Classification based on functional analysis indicated that a large
number of these genes were involved in brain development and neurogenesis,
including genes involved in Wingless (Wnt) and Notch signaling pathways.
In addition, the expression levels of numerous genes involved in
the stress and inflammatory responses, as well as apoptosis, were
affected by CR. Interestingly, we found that a number of genes involved
in the stress response and apoptosis were down-regulated in early
but up-regulated in late stage CR. The most notable finding was that
CR altered the expression of genes associated with the mammalian
target of the rapamycin (mTOR) nutrient sensing pathway, which has
recently been shown to be involved in the regulation of energy intake
and aging. By applying rapamycin, a specific pharmacological inhibitor
of mTOR signaling, we found that the inhibition of mTOR could significantly
prevent neuronal apoptosis induced by Paraquat. Taken together, our
results provided not only a systematic expression profile of the
hypothalamic response to CR, but also revealed the linkage between
CR and mTOR signaling in the neuroprotection in mice.},
issn = {0047-6374},
keywords = {Calorie restriction, Hypothalamus, mTOR, Aging, Microarray, Mice},
url = {http://www.sciencedirect.com/science/article/B6T31-4WWG30P-1/2/87445b5ec0673cc016195ba7bc5506fe}
}
@ARTICLE{Wu2011j,
author = {Shengqian Q. Wu and Miguel Otero and Frank M. Unger and Mary B. Goldring
and Ampai Phrutivorapongkul and Catharina Chiari and Alexander Kolb
and Helmut Viernstein and Stefan Toegel},
title = {Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract
in human chondrocytes and macrophages},
journal = {Journal of Ethnopharmacology},
year = {2011},
volume = {138},
pages = {364 - 372},
number = {2},
abstract = {Ethnopharmacological relevance Caesalpinia sappan is a common remedy
in Traditional Chinese Medicine and possesses diverse biological
activities including anti-inflammatory properties. Osteoarthritis
(OA) is a degenerative joint disease with an inflammatory component
that drives the degradation of cartilage extracellular matrix. In
order to provide a scientific basis for the applicability of Caesalpinia
sappan in arthritic diseases, the present study aimed to assess the
effects of an ethanolic Caesalpinia sappan extract (CSE) on human
chondrocytes and macrophages. Materials and methods Primary human
chondrocytes were isolated from cartilage specimens of OA patients.
Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved
and pretreated with different concentrations of CSE prior to stimulation
with 10 ng/ml of interleukin-1beta (IL-1β) or lipopolysaccharide
(LPS). Following viability tests, nitric oxide (NO) and tumor necrosis
factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively.
Using validated real-time PCR assays, mRNA levels of IL-1β, TNF-α,
inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)
were quantified. SW1353 cells were cotransfected with a COX-2 luciferase
reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65
expression vectors in the presence or absence of CSE. Results CSE
dose-dependently inhibited the expression of pro-inflammatory cytokines
IL-1β and TNF-α in IL-1β-stimulated chondrocytes and LPS-stimulated
THP-1 macrophages. CSE further suppressed the synthesis of NO in
primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition
of COX-2 transcription was found to be related with the CSE inhibition
of the p65/p50-driven transactivation of the COX-2 promoter. Conclusions
The present report is first to demonstrate the anti-inflammatory
activity of CSE in an in vitro cell model of joint inflammation.
CSE can effectively abrogate the IL-1β-induced over-expression of
inflammatory mediators at the transcriptional level in human chondrocytes
and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling.
Blockade of IL-1β-induced NF-κB signaling and its downstream pro-inflammatory
targets by CSE may be beneficial for reducing cartilage breakdown
in arthritis.},
doi = {10.1016/j.jep.2011.09.011},
issn = {0378-8741},
keywords = {Osteoarthritis},
url = {http://www.sciencedirect.com/science/article/pii/S0378874111006660}
}
@ARTICLE{Wu2008c,
author = {Wu, Shun-Chi and Chang, Shin C. and Wu, Hung-Yi and Liao, Pei-Ju
and Chang, Ming-Fu},
title = {Hepatitis C Virus NS5A Protein Down-regulates the Expression of Spindle
Gene Aspm through PKR-p38 Signaling Pathway},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {29396--29404},
number = {43},
month = oct,
abstract = {Hepatitis C virus often causes persistent infection and hepatocellular
carcinoma. Studies have demonstrated the roles of viral nonstructural
protein 5A (NS5A) in the induction of chromosome aneuploidy, but
the molecular mechanisms are not clear. In this study, hydrodynamics-based
in vivo transfection was applied to a mouse system. Mouse hepatocytes
that successfully expressed NS5A protein were isolated by laser capture
microdissection. Gene expression profiles of the NS5A-expressing
hepatocytes were examined by an Affymetrix oligonucleotide microarray
system. Aspm (abnormal spindle-like, microcephaly associated), which
encodes the mitotic spindle protein ASPM, was identified to be differentially
expressed in the absence and the presence of NS5A. The down-regulation
of Aspm mRNA and ASPM protein was confirmed by real time polymerase
chain reaction and Western blot analysis, respectively, both in mouse
model systems and in viral subgenomic replicon and in vitro transfection
culturing systems. In addition, cultured cells that constitutively
expressed NS5A protein showed G2/M cell cycle block and chromosome
aneuploidy. Overexpression of ASPM relieved the G2/M cell cycle block.
Furthermore, NS5A protein repressed the promoter activity of Aspm
gene in a dose-dependent manner. The regulatory effect was abolished
when amino acid substitutions P2209L, T2214A, and T2217G known to
interrupt the NS5A-PKR interaction were introduced into the NS5A
protein. This indicates that the down-regulation of Aspm expression
is via the PKR-p38 signaling pathway. These results suggest that
NS5A protein down-regulates the expression of the mitotic spindle
protein ASPM and induces aberrant mitotic cell cycle associated with
chromosome instability and hepatocellular carcinoma.},
url = {http://www.jbc.org/cgi/content/abstract/283/43/29396}
}
@ARTICLE{Wu2004,
author = {Wu, Shao-Ming and Baxendale, Vanessa and Chen, Yali and Lap-Yin Pang,
Alan and Stitely, Timothy and Munson, Peter J. and Yiu-Kwong Leung,
Michael and Ravindranath, Neelakanta and Dym, Martin and Rennert,
Owen M. and Chan, Wai-Yee},
title = {Analysis of mouse germ-cell transcriptome at different stages of
spermatogenesis by SAGE: Biological significance},
journal = {Genomics},
year = {2004},
volume = {84},
pages = {971--981},
number = {6},
month = dec,
abstract = {The transcriptomes of mouse type A spermatogonia (Spga), pachytene
spermatocytes (Spcy), and round spermatids (Sptd) were determined
by sequencing the respective SAGE (Serial Analysis of Gene Expression)
libraries. A total of 444,015 tags derived from one Spga, two Spcy,
and one Sptd library were analyzed, and 34,619 different species
of transcripts were identified, 5279 of which were novel. Results
indicated the germ-cell transcriptome comprises of more than 30,000
transcripts. Virtual subtraction showed that cell-specific transcripts
constitute 12-19.5% of the transcriptome. Components of the protein
biosynthetic machinery are highly expressed in Spga. In Spcy transcription
factors are abundantly expressed while transcripts encoding proteins
involved in chromosome remodeling and testis-specific transcripts
are prominent in Sptd. The databases generated by this work provide
very useful resources for cellular localization of genes in silico.
They are also extremely useful as sources for identification of splice
variants of genes in germ cells.},
issn = {0888-7543},
keywords = {Expression profiling, SAGE, Spermatogonia, Spermatocyte, Spermatid,
Spermatogenesis},
url = {http://www.sciencedirect.com/science/article/B6WG1-4DD94SJ-1/2/382d047f00e1bf3dc845483294dcfde7}
}
@ARTICLE{Wu2005a,
author = {Wu, Tinghuai and Handa, James T. and Gottsch, John D.},
title = {Light-Induced Oxidative Stress in Choroidal Endothelial Cells in
Mice},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2005},
volume = {46},
pages = {1117--1123},
number = {4},
month = apr,
abstract = {PURPOSE. Although light-induced oxidative stress in the retina has
been extensively reported, little information regarding light-induced
oxidative stress in choroidal endothelial cells (CECs) is available.
In the current study, light-induced DNA oxidation and the activation
of nuclear factor-{kappa}B (NF-{kappa}B), a major oxidative responsive
transcription factor, were investigated in mouse CECs. METHODS. Mice
were exposed to green light. Light-induced DNA oxidation in CECs
was detected by in situ 8-hydroxy-2-deoxyguanosine (8-oxo-dG) immunolabeling.
CECs were isolated from the retinal pigment epithelium (RPE)/choroid
by using immunomagnetic beads. The isolated CECs were immunochemically
characterized by the expression of endothelial markers, CD31, and
P1H12. The quality of total RNA from CECs was assessed by a bioanalyzer
and RT-PCR. NF-{kappa}B activation in situ and in isolated CECs was
investigated. RESULTS. After a 3-hour exposure to light, the immunoreactivity
to anti-8-oxo-dG antibody or anti-NF-{kappa}B p65 antibody in CECs
in situ was significantly increased when compared with unexposed
mice. Isolated CECs expressed CD31 and P1H12. The 28S/18S rRNA ratio
of RNA isolated from CECs was 1.5:1. CD31 and von Willebrand Factor
(vWF) transcripts were predominantly expressed in the RNA from isolated
CECs. I{kappa}B{alpha} was more heavily phosphorylated in light-exposed
than untreated CECs. I{kappa}B{alpha} expression levels were increased
fivefold in isolated CECs after exposure to light compared to unexposed
control subjects. CONCLUSIONS. Exposure to light induces oxidative
stress in CECs in vivo. A method for CEC isolation from the mouse
RPE/choroid with preservation of RNA quality has been developed.
The results of this study may facilitate the ability to identify
CEC-specific genes and gene products that respond to photo-oxidative
stress.},
url = {http://www.iovs.org/cgi/content/abstract/46/4/1117}
}
@ARTICLE{Wu2011b,
author = {Tse-Yu Wu and Brooke L. Fridley and Gregory D. Jenkins and Anthony
Batzler and Liewei Wang and Richard M. Weinshilboum},
title = {Mycophenolic acid response biomarkers: A cell line model system-based
genome-wide screen},
journal = {International Immunopharmacology},
year = {2011},
volume = {11},
pages = {1057 - 1064},
number = {8},
abstract = {Mycophenolic acid (MPA) is commonly used to treat patients with solid
organ transplants during maintenance immunosuppressive therapy. Response
to MPA varies widely, both for efficacy and drug-induced toxicity.
A portion of this variation can be explained by pharmacokinetic and
pharmacodynamic factors, including genetic variation in MPA-metabolizing
UDP-glucuronyltransferase isoforms and the MPA targets, inosine monophosphate
dehydrogenase 1 and 2. However, much of the variation in MPA response
presently remains unexplained. We set out to determine whether there
might be additional genes that modify response to MPA by performing
a genome-wide association study between basal gene mRNA expression
profiles and an MPA cytotoxicity phenotype using a 271 human lymphoblastoid
cell line model system to identify and functionally validate genes
that might contribute to variation in MPA response. Our association
study identified 41 gene expression probe sets, corresponding to
35 genes, that were associated with MPA cytotoxicity as a drug response
phenotype (p < 1 × 10−6). Follow-up siRNA-mediated
knockdown-based functional validation identified four of these candidate
genes, C17orf108, CYBRD1, NASP, and RRM2, whose knockdown shifted
the MPA cytotoxicity curves in the direction predicted by the association
analysis. These studies have identified novel candidate genes that
may contribute to variation in response to MPA therapy and, as a
result, may help make it possible to move toward more highly individualized
MPA-based immunosuppressive therapy.},
doi = {10.1016/j.intimp.2011.02.027},
issn = {1567-5769},
keywords = {Mycophenolic acid},
url = {http://www.sciencedirect.com/science/article/pii/S1567576911001196}
}
@ARTICLE{Wu2009d,
author = {Wu, Xiaofang and Ghimbovschi, Svetlana and Aujla, Pawandeep K. and
Rose, Mary C. and Pena, Maria T.},
title = {Expression Profiling of Inflammatory Mediators in Pediatric Sinus
Mucosa},
journal = {Arch Otolaryngol Head Neck Surg},
year = {2009},
volume = {135},
pages = {65--72},
number = {1},
month = jan,
abstract = {Objective To evaluate gene expression by microarray analyses of inflammatory
mediators in the sinus mucosa of children with and without chronic
rhinosinusitis (CRS). Design Prospective molecular genetics analysis.
Setting Children's National Medical Center, Washington, DC. Subjects
Eleven patients with CRS who underwent endoscopic sinus surgery and
10 control children who underwent craniofacial resection or neurosurgical
procedures. Main Outcome Measures Gene expression levels of sinus
tissue from 6 patients with CRS and 6 controls and messenger RNA
expression levels of upregulated inflammatory/immune response genes,
as well as cytokines of interest, determined by quantitative reverse
transcription-polymerase chain reaction. Results Gene expression
using the Plier algorithm yielded the most consistent grouping of
samples: 96 genes were significantly upregulated more than 2-fold,
and 123 genes were downregulated by at least 50% in the CRS sinus
tissues compared with controls (P < .05). GeneSpring analysis demonstrated
significant changes in several ontology categories in the CRS samples,
including inflammatory/immune response genes. The chemokines CXCL13
and CXCL5, serum amyloid A, serpin B4, and defensin {beta}1 were
highly upregulated ([≥]5-fold). Increased expression of these
genes was validated by quantitative reverse transcription-polymerase
chain reaction in an independent set of tissues. Expression levels
of interleukins 5, 6, and 8 were similar in both cohorts; these results
were validated by reverse transcription-polymerase chain reaction.
Conclusions Microarray analyses of sinus mucosa in children with
CRS showed an increased expression of inflammatory genes involved
in innate and adaptive immune systems. This technology can be successfully
used to identify genes implicated in the pathogenesis of pediatric
CRS.},
url = {http://archotol.ama-assn.org/cgi/content/abstract/135/1/65}
}
@ARTICLE{Wu2010b,
author = {Wu, Xianli and Kang, Jie and Xie, Chenghui and Burris, Ramona and
Ferguson, Matthew E. and Badger, Thomas M. and Nagarajan, Shanmugam},
title = {Dietary Blueberries Attenuate Atherosclerosis in Apolipoprotein E-Deficient
Mice by Upregulating Antioxidant Enzyme Expression},
journal = {J. Nutr.},
year = {2010},
volume = {140},
pages = {1628--1632},
number = {9},
month = sep,
abstract = {Protective effects of blueberries (BB) against atherosclerosis and
potential underlying mechanisms in reducing oxidative stress were
examined in apoE-deficient (apoE- / -) mice. ApoE- / - mice were
fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried
whole BB for 20 wk. The mean lesion area for apoE- / - mice fed BB
was reduced by 39% (P lt 0.001) in the aorta sinus and 58% (P lt
0.001) in the descending aorta compared with CD-fed mice. These atheroprotective
effects were independent of the serum lipid profile or total antioxidant
capacity (as measured by oxygen radical absorbance capacity). The
concentration of a biomarker of lipid peroxidation, F2-isoprostane,
was lower in liver of BB-fed mice (P lt 0.05). Genes analyzed by
RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide
dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin
reductase 1] were upregulated in BB-fed mice. Enzyme activities of
SOD and GSR were greater (P lt 0.05) in liver and/or serum of BB-fed
mice than those of CD-fed mice. In addition, serum paraoxonase 1
activity in serum of BB-fed mice was also greater than that of CD-fed
mice (P lt 0.05) at the end of the study. These results suggest a
protective effectiveness of BB against atherosclerosis in this apoE-
/ - mouse model. The potential mechanisms may involve reduction in
oxidative stress by both inhibition of lipid peroxidation and enhancement
of antioxidant defense.},
url = {http://jn.nutrition.org/cgi/content/abstract/140/9/1628}
}
@ARTICLE{Wu2011f,
author = {Wu, Xuxia and Patki, Amit and Lara-Castro, Cristina and Cui, Xiangqin
and Zhang, Kui and Walton, R. Grace and Osier, Michael V. and Gadbury,
Gary L. and Allison, David B. and Martin, Mitchell and Garvey, W.
Timothy},
title = {Genes and biochemical pathways in human skeletal muscle affecting
resting energy expenditure and fuel partitioning},
journal = {J Appl Physiol},
year = {2011},
volume = {110},
pages = {746--755},
number = {3},
month = mar,
abstract = {Genes influencing resting energy expenditure (REE) and respiratory
quotient (RQ) represent candidate genes for obesity and the metabolic
syndrome because of the involvement of these traits in energy balance
and substrate oxidation. We aim to explore the molecular basis for
individual variation in REE and fuel partitioning as reflected by
RQ. We performed microarray studies in human vastus lateralis muscle
biopsies from 40 healthy subjects with measured REE and RQ values.
We identified 2,392 and 1,115 genes significantly correlated with
REE and RQ, respectively. Genes correlated with REE and RQ encompass
a broad array of functions, including carbohydrate and lipid metabolism,
gene expression, mitochondrial processes, and membrane transport.
Microarray pathway analysis revealed that REE was positively correlated
with upregulation of G protein-coupled receptor signaling (meet criteria/total
genes: 65 of 283) involved in autonomic nervous system functions,
including those receptors mediating adrenergic, dopamine, {gamma}-aminobutyric
acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total
genes: 46 of 176). Reduced REE was associated with an increase in
genes participating in ubiquitin-proteasome-dependent proteolytic
pathways (58 of 232). Serine-type peptidase activity (9 of 76) was
positively correlated with RQ, while genes involved in the protein
phosphatase type 2A complex (4 of 9), mitochondrial function and
cellular respiration (38 of 315), and unfolded protein binding (19
of 97) were associated with reduced RQ values and a preference for
lipid fuel metabolism. Individual variations in whole body REE and
RQ are regulated by differential expressions of specific genes and
pathways intrinsic to skeletal muscle.},
comment = {10.1152/japplphysiol.00293.2010},
url = {http://jap.physiology.org/cgi/content/abstract/110/3/746}
}
@ARTICLE{Wu2009e,
author = {Wu, Xin and Schmidt, Jonathan A. and Avarbock, Mary R. and Tobias,
John W. and Carlson, Claire A. and Kolon, Thomas F. and Ginsberg,
Jill P. and Brinster, Ralph L.},
title = {Prepubertal human spermatogonia and mouse gonocytes share conserved
gene expression of germline stem cell regulatory molecules},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {21672--21677},
number = {51},
month = dec,
abstract = {In the human testis, beginning at {approx}2 months of age, gonocytes
are replaced by adult dark (Ad) and pale (Ap) spermatogonia that
make up the spermatogonial stem cell (SSC) pool. In mice, the SSC
pool arises from gonocytes {approx}6 days after birth. During puberty
in both species, complete spermatogenesis is established by cells
that differentiate from SSCs. Essentially pure populations of prepubertal
human spermatogonia and mouse gonocytes were selected from testis
biopsies and validated by confirming the presence of specific marker
proteins in cells. Stem cell potential of germ cells was demonstrated
by transplantation to mouse testes, following which the cells migrated
to the basement membrane of the seminiferous tubule and were maintained
similar to SSCs. Differential gene expression profiles generated
between germ cells and testis somatic cells demonstrated that expression
of genes previously identified as SSC and spermatogonial-specific
markers (e.g., zinc-finger and BTB-domain containing 16, ZBTB16)
was greatly elevated in both human spermatogonia and mouse gonocytes
compared to somatic cells. Several genes were expressed at significantly
higher levels in germ cells of both species. Most importantly, genes
known to be essential for mouse SSC self-renewal (e.g., Ret proto-oncogene,
Ret; GDNF-family receptor {alpha}1, Gfr{alpha}1; and B-cell CLL/lymphoma
6, member B, Bcl6b) were more highly expressed in both prepubertal
human spermatogonia and mouse gonocytes than in somatic cells. The
results indicate remarkable conservation of gene expression, notably
for self-renewal genes, in these prepubertal germline cells between
two species that diverged phylogenetically {approx}75 million years
ago.},
url = {http://www.pnas.org/cgi/content/abstract/106/51/21672}
}
@ARTICLE{Wu2011e,
author = {Wu, Xue-mei and Shao, Xiang-qiang and Meng, Xian-xin and Zhang, Xiao-na
and Zhu, Li and Liu, Shi-xu and Lin, Jian and Xiao, Hua-sheng},
title = {Genome-wide analysis of microRNA and mRNA expression signatures in
hydroxycamptothecin-resistant gastric cancer cells},
journal = {Acta Pharmacol Sin},
year = {2011},
volume = {32},
pages = {259--269},
number = {2},
month = feb,
issn = {1671-4083},
publisher = {CPS and SIMM},
url = {http://dx.doi.org/10.1038/aps.2010.204}
}
@ARTICLE{Wu2011i,
author = {Wu, Yufeng and Kikuchi, Shinji and Yan, Huihuang and Zhang, Wenli
and Rosenbaum, Heidi and Iniguez, A. Leonardo and Jiang, Jiming},
title = {Euchromatic Subdomains in Rice Centromeres Are Associated with Genes
and Transcription},
journal = {PLANT CELL},
year = {2011},
volume = {23},
pages = {4054-4064},
number = {11},
abstract = {The presence of the centromere-specific histone H3 variant, CENH3,
defines centromeric (CEN) chromatin, but poorly understood epigenetic
mechanisms determine its establishment and maintenance. CEN chromatin
is embedded within pericentromeric heterochromatin in most higher
eukaryotes, but, interestingly, it can show euchromatic characteristics;
for example, the euchromatic histone modification mark dimethylated
H3 Lys 4 (H3K4me2) is uniquely associated with animal centromeres.
To examine the histone marks and chromatin properties of plant centromeres,
we developed a genomic tiling array for four fully sequenced rice
(Oryza sativa) centromeres and used chromatin immunoprecipitation-chip
to study the patterns of four euchromatic histone modification marks:
H3K4me2, trimethylated H3 Lys 4, trimethylated H3 Lys 36, and acetylated
H3 Lys 4, 9. The vast majority of the four histone marks were associated
with genes located in the H3 subdomains within the centromere cores.
We demonstrate that H3K4me2 is not a ubiquitous component of rice
CEN chromatin, and the euchromatic characteristics of rice CEN chromatin
are hallmarks of the transcribed sequences embedded in the centromeric
H3 subdomains. We propose that the transcribed sequences located
in rice centromeres may provide a barrier preventing loading of CENH3
into the H3 subdomains. The separation of CENH3 and H3 subdomains
in the centromere core may be favorable for the formation of three-dimensional
centromere structure and for rice centromere function.},
doi = {10.1105/tpc.111.090043},
eprint = {http://www.plantcell.org/cgi/reprint/23/11/4054.pdf},
url = {http://www.plantcell.org/cgi/content/abstract/23/11/4054}
}
@ARTICLE{Wu2009f,
author = {Wu, YingJie and Sun, Hui and Yakar, Shoshana and LeRoith, Derek},
title = {Elevated Levels of Insulin-Like Growth Factor (IGF)-I in Serum Rescue
the Severe Growth Retardation of IGF-I Null Mice},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {4395--4403},
number = {9},
month = sep,
abstract = {IGF-I plays a vital role in growth and development and acts in an
endocrine and an autocrine/paracrine fashion. The purpose of the
current study was to clarify whether elevated levels of IGF-I in
serum can rescue the severe growth retardation and organ development
and function of igf-I null mice. To address that, we overexpressed
a rat igf-I transgene specifically in the liver of igf-I null mice.
We found that in the total absence of tissue IGF-I, elevated levels
of IGF-I in serum can support normal body size at puberty and after
puberty but are insufficient to fully support the female reproductive
system (evident by irregular estrous cycle, impaired development
of ovarian corpus luteum, reduced number of uterine glands and endometrial
hypoplasia, all leading to decreased number of pregnancies and litter
size). We conclude that most autocrine/paracrine actions of IGF-I
that determine organ growth and function can be compensated by elevated
levels of endocrine IGF-I. However, in mice, full compensatory responses
are evident later in development, suggesting that autocrine/paracrine
IGF-I is critical for neonatal development. Furthermore, we show
that tissue IGF-I is necessary for the development of the female
reproductive system and cannot be compensated by elevated levels
of serum IGF-I.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/9/4395}
}
@ARTICLE{Wu2004a,
author = {Wu, Yongfei and Zhang, Dongsheng and Lou, Danwen and Fan, Yunxia
and Aronow, Bruce and Xu, Ming and Zhang, Jianhua},
title = {c-fos regulates neuropeptide Y expression in mouse dentate gyrus},
journal = {Neuroscience Letters},
year = {2004},
volume = {363},
pages = {6--10},
number = {1},
month = jun,
abstract = {Excitotoxicity by which excitatory amino acid induces neuronal cell
death may underlie mechanisms of neurodegenerative diseases. We previously
found that c-fos is critically involved in neuronal excitability
and survival. Mice that carry hippocampal mutations of c-fos exhibited
hyper-excitability, hyper-excitotoxicity and higher mortality in
kainic acid (KA)-induced seizures compared to wild-type mice. To
further understand the neuroprotective signal transduction pathways
regulated by c-fos in the hippocampal formation, we identified 172
genes that are either regulated by KA or are differentially expressed
in wild-type and hippocampal-specific c-fos mutant mice using cDNA
microarrays. One gene encodes the neuropeptide Y (NPY). We confirmed
that c-fos regulates the expression of NPY by using immunohistochemistry.
We found that c-fos is critical in up-regulation of NPY expression
in the granule cell layer of dentate gyrus in response to KA administration.
As NPY is an important endogenous anti-epileptic agent, our result
is consistent with a hypothesis that the neuroprotective function
of c-fos is mediated in part by regulation of NPY expression.},
issn = {0304-3940},
keywords = {c-fos, Neuropeptide Y, Epilepsy, Kainic acid, Knockout, Hippocampal
formation},
url = {http://www.sciencedirect.com/science/article/B6T0G-4CB68W8-D/2/2be77a9ddb1cc286fb00b339ac13f2be}
}
@ARTICLE{Wu2010,
author = {Wu, Yong and Zhao, Weidong and Zhao, Jingbo and Zhang, Yuanfei and
Qin, Weiping and Pan, Jiangping and Bauman, William A. and Blitzer,
Robert D. and Cardozo, Christopher},
title = {REDD1 Is a Major Target of Testosterone Action in Preventing Dexamethasone-Induced
Muscle Loss},
journal = {Endocrinology},
year = {2010},
volume = {151},
pages = {1050--1059},
number = {3},
month = mar,
abstract = {Glucocorticoids are a well-recognized and common cause of muscle atrophy
that can be prevented by testosterone. However, the molecular mechanisms
underlying such protection have not been described. Thus, the global
effects of testosterone on dexamethasone-induced changes in gene
expression were evaluated in rat gastrocnemius muscle using DNA microarrays.
Gene expression was analyzed after 7-d administration of dexamethasone,
dexamethasone plus testosterone, or vehicle. Dexamethasone changed
expression of 876 probe sets by at least 2-fold. Among these, 474
probe sets were changed by at least 2-fold in the opposite direction
in the dexamethasone plus testosterone group (genes in opposition).
Major biological themes represented by genes in opposition included
IGF-I signaling, myogenesis and muscle development, and cell cycle
progression. Testosterone completely prevented the 22-fold increase
in expression of the mammalian target of rapamycin (mTOR) inhibitor
regulated in development and DNA damage responses 1 (REDD1), and
attenuated dexamethasone induced increased expression of eIF4E binding
protein 1, Forkhead box O1, and the p85 regulatory subunit of the
IGF-I receptor but prevented decreased expression of IRS-1. Testosterone
attenuated increases in REDD1 protein in skeletal muscle and L6 myoblasts
and prevented dephosphorylation of p70S6 kinase at the mTOR-dependent
site Thr389 in L6 myoblast cells. Effects of testosterone on REDD1
mRNA levels occurred within 1 h, required the androgen receptor,
were blocked by bicalutamide, and were due to inhibition of transcriptional
activation of REDD1 by dexamethasone. These data suggest that testosterone
blocks dexamethasone-induced changes in expression of REDD1 and other
genes that collectively would otherwise down-regulate mTOR activity
and hence also down-regulate protein synthesis.},
url = {http://endo.endojournals.org/cgi/content/abstract/151/3/1050}
}
@ARTICLE{Wu2008d,
author = {Wu, Zuopeng and Jia, Xinying and de la Cruz, Laura and Su, Xun-Cheng
and Marzolf, Bruz and Troisch, Pamela and Zak, Daniel and Hamilton,
Adam and Whittle, Belinda and Yu, Di and Sheahan, Daniel and Bertram,
Edward and Aderem, Alan and Otting, Gottfried and Goodnow, Christopher
C. and Hoyne, Gerard F.},
title = {Memory T Cell RNA Rearrangement Programmed by Heterogeneous Nuclear
Ribonucleoprotein hnRNPLL},
journal = {Immunity},
year = {2008},
volume = {29},
pages = {863--875},
number = {6},
month = dec,
abstract = {Summary Differentiation of memory cells involves DNA-sequence changes
in B lymphocytes but is less clearly defined in T cells. RNA rearrangement
is identified here as a key event in memory T cell differentiation
by analysis of a mouse mutation that altered the proportions of naive
and memory T cells and crippled the process of Ptprc exon silencing
needed to generate CD45RO in memory T cells. A single substitution
in a memory-induced RNA-binding protein, hnRNPLL, destabilized an
RNA-recognition domain that bound with micromolar affinity to RNA
containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively
diminished T cell accumulation in peripheral lymphoid tissues but
not proliferation. Exon-array analysis of Hnrpll mutant naive and
memory T cells revealed an extensive program of alternative mRNA
splicing in memory T cells, coordinated by hnRNPLL. A remarkable
overlap with alternative splicing in neural tissues may reflect a
co-opted strategy for diversifying memory T cells.},
issn = {1074-7613},
url = {http://www.sciencedirect.com/science/article/B6WSP-4V5PHVG-7/2/a983e605ed25752c83017004c94d63f6}
}
@ARTICLE{Wu2006a,
author = {Wu, Zhi-Liang and Ciallella, John R. and Flood, Dorothy G. and O'Kane,
Teresa M. and Bozyczko-Coyne, Donna and Savage, Mary J.},
title = {Comparative analysis of cortical gene expression in mouse models
of Alzheimer's disease},
journal = {Neurobiology of Aging},
year = {2006},
volume = {27},
pages = {377--386},
number = {3},
month = mar,
abstract = {Three mouse models of Alzheimer's disease (AD) were used to assess
changes in gene expression potentially critical to amyloid [beta]-peptide
(A[beta])-induced neuronal dysfunction. One mouse model harbored
homozygous familial AD (FAD) knock-in mutations in both, amyloid
precursor protein (APP) and presenilin 1 (PS-1) genes (APPNLh/NLh/PS-1P264L/P264L),
the other two models harbored APP over-expression of FAD mutations
(Tg2576) with the PS-1 knock-in mutation at either one or two alleles.
These mouse models of AD had varying levels of A[beta]40 and A[beta]42
and different latencies and rates of A[beta] deposition in brain.
To assess changes in gene expression associated with A[beta] accumulation,
the Affymetrix murine genome array U74A was used to survey gene expression
in the cortex of these three models both prior to and following A[beta]
deposition. Altered genes were identified by comparing the AD models
with age-matched control littermates. Thirty-four gene changes were
identified in common among the three models in mice with A[beta]
deposition. Among the up-regulated genes, three major classes were
identified that encoded for proteins involved in immune responses,
carbohydrate metabolism, and proteolysis. Down-regulated genes of
note included pituitary adenylate cyclase-activating peptide (PACAP),
brain-derived neurotrophic factor (BDNF), and insulin-like growth
factor I receptor (IGF-IR). In young mice without detectable A[beta]
deposition, there were no regulated genes common among the three
models, although 40 genes were similarly altered between the two
Tg2576 models with the PS-1 FAD knock-in. Finally, changes in gene
expression among the three mouse models of AD were compared with
those reported in human AD samples. Sixty-nine up-regulated and 147
down-regulated genes were found in common with human AD brain. These
comparisons across different genetic mouse models of AD and human
AD brain provide greater support for the involvement of identified
gene expression changes in the neuronal dysfunction and cognitive
deficits accompanying amyloid deposition in mammalian brain.},
issn = {0197-4580},
keywords = {Gene expression, Alzheimer's disease, A[beta], Mouse model},
url = {http://www.sciencedirect.com/science/article/B6T09-4G94HGD-1/2/46f22f3192954320c6bc007f848ba8d6}
}
@ARTICLE{Wuchty2010,
author = {Wuchty, Stefan and Zhang, Alice and Walling, Jennifer and Ahn, Susie
and Li, Aiguo and Quezado, Martha and Oberholtzer, Carl and Zenklusen,
Jean-Claude and Fine, Howard A.},
title = {Gene pathways and subnetworks distinguish between major glioma subtypes
and elucidate potential underlying biology},
journal = {Journal of Biomedical Informatics},
year = {2010},
volume = {43},
pages = {945--952},
number = {6},
month = dec,
abstract = {Molecular diagnostic tools are increasingly being used in an attempt
to classify primary human brain tumors more accurately. While methods
that are based on the analysis of individual gene expression prove
to be useful for diagnostic purposes, they are devoid of biological
significance since tumorgenesis is a concerted deregulation of multiple
pathways rather than single genes. In a proof of concept, we utilize
two large clinical data sets and show that the elucidation of enriched
pathways and small differentially expressed sub-networks of protein
interactions allow a reliable classification of glioblastomas and
oligodendrogliomas. Applying a feature selection method, we observe
that an optimized subset of pathways and subnetworks significantly
improves the prediction accuracy. By determining the enrichment of
altered genes in pathways and subnetworks we show that optimized
subsets of genes rarely seem to be a target of genomic alteration.
Our results suggest that groups of genes play a decisive role for
the phenotype of the underlying tumor samples that can be utilized
to reliably distinguish tumor types. In the absence of enrichment
of genes that are genomically altered we assume that genetic changes
largely exert an indirect rather than direct regulatory influence
on a number of tumor-defining regulatory networks.},
issn = {1532-0464},
keywords = {Classification, Gliomas, Subnetworks, Pathways},
url = {http://www.sciencedirect.com/science/article/pii/S1532046410001322}
}
@ARTICLE{Wunderink2011a,
author = {Wunderink, Yvette S. and Engels, Steef and Halm, Silke and Yúfera,
Manuel and Martínez-Rodríguez, Gonzalo and Flik, Gert and Klaren,
Peter H.M. and Mancera, Juan M.},
title = {Chronic and acute stress responses in Senegalese sole (Solea senegalensis):
The involvement of cortisol, CRH and CRH-BP},
journal = {General and Comparative Endocrinology},
year = {2011},
volume = {171},
pages = {203--210},
number = {2},
month = apr,
abstract = {The hypothalamus-pituitary-interrenal (HPI) axis is pivotal in the
endocrine stress response of fish. Hypothalamic corticotropin-releasing
hormone (CRH) initiates the endocrine stress response and stimulates
the release of adrenocorticotropic hormone (ACTH) from the pituitary
pars distalis, which in turn activates cortisol production and release
by the interrenal cells of the head kidney. CRH activity depends
on the levels of a specific CRH binding protein (CRH-BP). We have
characterized the cDNAs coding for CRH and CRH-BP in Senegalese sole
(Solea senegalensis) and investigated their mRNA expression in juveniles
that were submitted to a protocol that involved exposure to a chronic
stressor (viz. increased cultivation densities) followed by an acute
stressor (viz. transfer to increased ambient salinity). Juveniles
were cultivated at three densities (1.9, 4.7 and 9.8 kg/m2) for 33 days,
and then exposed to an osmotic challenge that involved transfer from
seawater (39[per mille sign] salinity, SW) to hypersaline seawater
(55[per mille sign], HSW). The highest density imposed stress as
indicated by elevated cortisol levels and CRH mRNA expression compared
to fish stocked at low density. Fish kept at high density differentially
responded to a posterior transfer to HSW; no cortisol or CRH response
was seen, but osmoregulatory and metabolic parameters were affected.
No differences in CRH-BP mRNA expression levels were found at different
stocking densities; transfer to HSW enhanced expression in both low
and high density stocked animals, suggesting that CRH-BP acts as
a modulator of the acute stress response, not so of the chronic stress
response. We conclude that stocking of Senegalese sole at high density
is a stressful condition that may compromise the capacity to cope
with subsequent stressors.},
issn = {0016-6480},
keywords = {Solea senegalensis, Cortisol, CRH, CRH-binding protein, Stress, Stocking
density, Salinity},
url = {http://www.sciencedirect.com/science/article/pii/S0016648011000268}
}
@ARTICLE{Wunderink2011,
author = {Yvette S. Wunderink and Erik de Vrieze and Juriaan R. Metz and Silke
Halm and Gonzalo MartÃnez-RodrÃguez and Gert Flik and Peter H.M.
Klaren and Juan M. Mancera},
title = {Subfunctionalization of POMC paralogues in Senegalese sole (Solea
senegalensis)},
journal = {General and Comparative Endocrinology},
year = {2011},
pages = { - },
number = {0},
abstract = {The precursor protein proopiomelanocortin (POMC) gives rise to a variety
of biologically active peptides through cell-specific posttranslational
processing. Two transcripts of pomc were found in the flatfish Solea
senegalensis (ssePOMC-A and ssePOMC-B), that most likely represent
subfunctionalized paralogues: ssePOMC-A lacks the N-terminal cleavage
site for β-MSH, whereas ssePOMC-B cannot yield ACTH and completely
lacks the opioid consensus sequence in the β-END region. An analysis
of nucleotide substitution rates shows that the POMC-derived peptides
possess well-conserved regions under purifying selection, except
the β-END derived from POMC-B, which has undergone positive selection.
The calculated Ks values for ssePOMC-A versus ssePOMC-B and zebrafish
POMCα versus zebrafish POMCβ are 0.40 and 0.72, respectively, indicating
that the zebrafish POMC paralogues started to evolve almost twice
as early in evolution, and that the Solea POMC paralogues arose independently
from the whole genome duplication event that gave rise to the zebrafish
paralogues. This makes ssePOMC-B the first identified POMCα orthologue
that lacks the opioid consensus. Furthermore, pomc-a expression is
down-regulated in chronic stressed S. senegalensis juveniles, whereas
pomc-b expression levels remain unaffected, indicating different
physiological roles for both POMC paralogues. The distribution of
functional POMC-derived peptide hormones over two pomc genes in S.
senegalensis suggests subfunctionalization of the paralogues, a relevant
notion when studying POMC function in endocrine responses.},
doi = {10.1016/j.ygcen.2011.11.026},
issn = {0016-6480},
keywords = {Evolution},
url = {http://www.sciencedirect.com/science/article/pii/S0016648011004400}
}
@ARTICLE{Wunderlich2005,
author = {Wunderlich, Frank and Dkhil, Mohamed A. and Mehnert, Liv I. and Braun,
Juliane V. and El-Khadragy, Manal and Borsch, Elena and Hermsen,
Derik and Benten, W. Peter M. and Pfeffer, Klaus and Mossmann, Horst
and Krücken, Jürgen},
title = {Testosterone responsiveness of spleen and liver in female lymphotoxin
[beta] receptor-deficient mice resistant to blood-stage malaria},
journal = {Microbes and Infection},
year = {2005},
volume = {7},
pages = {399--409},
number = {3},
month = mar,
abstract = {Disrupted signaling through lymphotoxin [beta] receptor (LT[beta]R)
results in severe defects of the spleen and even loss of all other
secondary lymphoid tissues, making mice susceptible to diverse infectious
agents. Surprisingly, however, we find that female LT[beta]R-deficient
mice are even more resistant to blood stages of Plasmodium chabaudi
malaria than wild-type C57BL/6 mice. Higher resistance of LT[beta]R-deficient
mice correlates with an earlier onset of reticulocytosis, and the
period of anemia is shorter. After surviving fulminant parasitemias
of about 35%, mice develop long-lasting protective immunity against
homologous rechallenge, with both spleen and liver acting as anti-malaria
effectors. Testosterone suppresses resistance, i.e. all mice succumb
to infections during or shortly after peak parasitemia. At peak parasitemia,
testosterone does not essentially affect cellularity and apoptosis
in the spleen, but aggravates liver pathology in terms of increased
cell swelling, numbers of apoptotic and binucleated cells and reduced
serum alkaline phosphatase levels, and conversely, reduces inflammatory
lymphocytic infiltrates in the liver. In the spleen, hybridization
of cDNA arrays identified only a few testosterone-induced changes
in gene expression, in particular upregulation of INF[gamma] and
IFN-regulated genes. By contrast, a much larger number of testosterone-affectable
genes was observed in the liver, including genes involved in regulation
of the extracellular matrix, in chemokine and cytokine signaling,
and in cell cycle control. Collectively, our data suggest that testosterone
dysregulates the inflammatory response in spleen and liver during
their differentiation to anti-malaria effectors in malaria-resistant
female LT[beta]R-deficient mice, thus contributing to the testosterone-induced
lethal outcome of malaria.},
issn = {1286-4579},
keywords = {Lymphotoxin beta-specific receptor, Plasmodium chabaudi, Malaria,
Testosterone, Anemia, cDNA microarrays},
url = {http://www.sciencedirect.com/science/article/B6VPN-4FK40VM-1/2/7d293c035c43d48ef2934194f28a3a45}
}
@ARTICLE{Wurmbach2007,
author = {Wurmbach, Elisa and Chen, Ying-bei and Khitrov, Greg and Zhang, Weijia
and Roayaie, Sasan and Schwartz, Myron and Fiel, Isabel and Thung,
Swan and Mazzaferro, Vincenzo and Bruix, Jordi and Bottinger, Erwin
and Friedman, Scott and Waxman, Samuel and Llovet, Josep M.},
title = {Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular
carcinoma},
journal = {Hepatology},
year = {2007},
volume = {45},
pages = {938--947},
number = {4},
abstract = {Abstract 10.1002/hep.21622.abs Although HCC is the third-leading cause
of cancer-related deaths worldwide, there is only an elemental understanding
of its molecular pathogenesis. In western countries, HCV infection
is the main etiology underlying this cancer's accelerating incidence.
To characterize the molecular events of the hepatocarcinogenic process,
and to identify new biomarkers for early HCC, the gene expression
profiles of 75 tissue samples were analyzed representing the stepwise
carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia)
to HCC, including 4 neoplastic stages (very early HCC to metastatic
tumors) from patients with HCV infection. We identified gene signatures
that accurately reflect the pathological progression of disease at
each stage. Eight genes distinguish between control and cirrhosis,
24 between cirrhosis and dysplasia, 93 between dysplasia and early
HCC, and 9 between early and advanced HCC. Using quantitative real-time
reverse-transcription PCR, we validated several novel molecular tissue
markers for early HCC diagnosis, specifically induction of abnormal
spindle-like, microcephaly-associated protein, hyaluronan-mediated
motility receptor, primase 1, erythropoietin, and neuregulin 1. In
addition, pathway analysis revealed dysregulation of the Notch and
Toll-like receptor pathways in cirrhosis, followed by deregulation
of several components of the Jak/STAT pathway in early carcinogenesis,
then upregulation of genes involved in DNA replication and repair
and cell cycle in late cancerous stages. Conclusion: These findings
provide a comprehensive molecular portrait of genomic changes in
progressive HCV-related HCC. (HEPATOLOGY 2007;45:938–947.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.21622}
}
@ARTICLE{Wurz2005,
author = {Wurz, Gregory T. and Read, Karla C. and Marchisano-Karpman, Cristina
and Gregg, Jeffrey P. and Beckett, Laurel A. and Yu, Qilu and DeGregorio,
Michael W.},
title = {Ospemifene inhibits the growth of dimethylbenzanthracene-induced
mammary tumors in Sencar mice},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2005},
volume = {97},
pages = {230--240},
number = {3},
month = nov,
abstract = {Ospemifene is a new selective estrogen receptor modulator (SERM) that
is being developed for the treatment of urogenital atrophy and osteoporosis.
Similarly to other SERMs, ospemifene exhibits antiestrogenic effects
in breast tissue, which led to the hypothesis that it may be a potential
breast cancer chemopreventive agent. We first assessed the ability
of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene
(DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18),
tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg,
were administered daily by oral gavage, in combination with 20 [mu]g
DMBA for the first 6 weeks. Control mice (N = 21) received vehicle
plus DMBA only for the first 6 weeks. Daily treatment then continued
for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence
of mammary carcinomas compared to control mice (p = 0.003), similar
to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant
effect was seen in mammary tumor prevention (p = 0.20). A follow-up
study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the
same model was then performed to confirm the results of the first
study. The results of the follow-up study, which extended the treatment
to 52 weeks, confirmed the results of our previous study, with ospemifene
(p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary
carcinomas compared to controls. The results of these two studies
suggest that women taking ospemifene for osteoporosis and/or urogenital
atrophy may further benefit from ospemifene's breast cancer chemopreventive
effects.},
issn = {0960-0760},
keywords = {Breast cancer, Chemoprevention, DMBA, Ospemifene, SERM},
url = {http://www.sciencedirect.com/science/article/B6T8X-4H2FXVT-3/2/9f58821a3fe833d8961bba03bc992b9e}
}
@ARTICLE{Wuttig2009,
author = {Wuttig, Daniela and Baier, Barbara and Fuessel, Susanne and Meinhardt,
Matthias and Herr, Alexander and Hoefling, Christian and Toma, Marieta
and Grimm, Marc-Oliver and Meye, Axel and Rolle, Axel and Wirth,
Manfred P.},
title = {Gene signatures of pulmonary metastases of renal cell carcinoma reflect
the disease-free interval and the number of metastases per patient},
journal = {Int. J. Cancer},
year = {2009},
volume = {125},
pages = {474--482},
number = {2},
abstract = {Abstract 10.1002/ijc.24353.abs Our understanding of metastatic spread
is limited and molecular mechanisms causing particular characteristics
of metastasis are largely unknown. Herein, transcriptome-wide expression
profiles of a unique cohort of 20 laser-resected pulmonary metastases
(Mets) of 18 patients with clear-cell renal cell carcinoma (RCC)
were analyzed to identify expression patterns associated with two
important prognostic factors in RCC: the disease-free interval (DFI)
after nephrectomy and the number of Mets per patient. Differentially
expressed genes were identified by comparing early (DFI ≤ 9 months)
and late (DFI ≥ 5 years) Mets, and Mets derived from patients with
few (≤8) and multiple (≥16) Mets. Early and late Mets could be
separated by the expression of genes involved in metastasis-associated
processes, such as angiogenesis, cell migration and adhesion (e.g.,
PECAM1, KDR). Samples from patients with multiple Mets showed an
elevated expression of genes associated with cell division and cell
cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number
of Mets might result from an increased growth potential. Minimal
sets of genes for the prediction of the DFI and the number of Mets
per patient were identified. Microarray results were confirmed by
quantitative PCR by including nine further pulmonary Mets of RCC.
In summary, we showed that subgroups of Mets are distinguishable
based on their expression profiles, which reflect the DFI and the
number of Mets of a patient. To what extent the identified molecular
factors contribute to the development of these characteristics of
metastatic spread needs to be analyzed in further studies. © 2009
UICC},
issn = {1097-0215},
keywords = {kidney cancer, lung metastases, oligonucleotide microarrays},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24353}
}
@ARTICLE{Wylie2010,
author = {Wylie, Christi J. and Hendricks, Timothy J. and Zhang, Bing and Wang,
Lily and Lu, Pengcheng and Leahy, Patrick and Fox, Stephanie and
Maeno, Hiroshi and Deneris, Evan S.},
title = {Distinct Transcriptomes Define Rostral and Caudal Serotonin Neurons},
journal = {J. Neurosci.},
year = {2010},
volume = {30},
pages = {670--684},
number = {2},
month = jan,
abstract = {The molecular architecture of developing serotonin (5HT) neurons is
poorly understood, yet its determination is likely to be essential
for elucidating functional heterogeneity of these cells and the contribution
of serotonergic dysfunction to disease pathogenesis. Here, we describe
the purification of postmitotic embryonic 5HT neurons by flow cytometry
for whole-genome microarray expression profiling of this unitary
monoaminergic neuron type. Our studies identified significantly enriched
expression of hundreds of unique genes in 5HT neurons, thus providing
an abundance of new serotonergic markers. Furthermore, we identified
several hundred transcripts encoding homeodomain, axon guidance,
cell adhesion, intracellular signaling, ion transport, and imprinted
genes associated with various neurodevelopmental disorders that were
differentially enriched in developing rostral and caudal 5HT neurons.
These findings suggested a homeodomain code that distinguishes rostral
and caudal 5HT neurons. Indeed, verification studies demonstrated
that Hmx homeodomain and Hox gene expression defined an Hmx+ rostral
subtype and Hox+ caudal subtype. Expression of engrailed genes in
a subset of 5HT neurons in the rostral domain further distinguished
two subtypes defined as Hmx+En+ and Hmx+En-. The differential enrichment
of gene sets for different canonical pathways and gene ontology categories
provided additional evidence for heterogeneity between rostral and
caudal 5HT neurons. These findings demonstrate a deep transcriptome
and biological pathway duality for neurons that give rise to the
ascending and descending serotonergic subsystems. Our databases provide
a rich, clinically relevant resource for definition of 5HT neuron
subtypes and elucidation of the genetic networks required for serotonergic
function.},
url = {http://www.jneurosci.org/cgi/content/abstract/30/2/670}
}
@ARTICLE{Wyrobek2011,
author = {A.J. Wyrobek and C.F. Manohar and V.V. Krishnan and D.O. Nelson and
M.R. Furtado and M.S. Bhattacharya and F. Marchetti and M.A. Coleman},
title = {Low dose radiation response curves, networks and pathways in human
lymphoblastoid cells exposed from 1 to 10\&xa0;cGy of acute gamma
radiation},
journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis},
year = {2011},
volume = {722},
pages = {119 - 130},
number = {2},
note = {Omics - Application and Impacts on Genotoxicity Assessment},
abstract = {We investigated the low dose dependency of the transcriptional response
of human cells to characterize the shape and biological functions
associated with the dose–response curve and to identify common
and conserved functions of low dose expressed genes across cells
and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals
were exposed to graded doses of radiation spanning the range of 1–10 cGy
were analyzed by transcriptome profiling, qPCR and bioinformatics,
in comparison to sham irradiated samples. A set of ∼80 genes showed
consistent responses in both cell lines; these genes were associated
with homeostasis mechanisms (e.g., membrane signaling, molecule transport),
subcellular locations (e.g., Golgi, and endoplasmic reticulum), and
involved diverse signal transduction pathways. The majority of radiation-modulated
genes had plateau-like responses across 1–10&xa0;cGy, some with
suggestive evidence that transcription was modulated at doses below
1&xa0;cGy. MYC, FOS and TP53 were the major network nodes of the
low-dose–response in HL cells. Comparison our low dose expression
findings in HL cells with those of prior studies in mouse brain after
whole body exposure, in human keratinocyte cultures, and in endothelial
cells cultures, indicates that certain components of the low dose
radiation response are broadly conserved across cell types and tissues,
independent of proliferation status.},
doi = {10.1016/j.mrgentox.2011.03.002},
issn = {1383-5718},
keywords = {Gene expression},
url = {http://www.sciencedirect.com/science/article/pii/S1383571811000684}
}
@ARTICLE{Wuerdemann2006,
author = {Würdemann, Chris and Peplies, Jörg and Schübbe, Sabrina and Ellrott,
Andreas and Schüler, Dirk and Glöckner, Frank Oliver},
title = {Evaluation of gene expression analysis using RNA-targeted partial
genome arrays},
journal = {Systematic and Applied Microbiology},
year = {2006},
volume = {29},
pages = {349--357},
number = {5},
month = jul,
abstract = {Highly parallel cDNA targeting microarrays have been established over
the last years as the quasi-standard for genome wide expression profiling
in pro- and eukaryotes. Protocols for the direct detection of RNA
or aRNA (amplified RNA) are currently emerging. This allows to circumvent
the bias introduced by enzymatic target molecule preparation. To
systematically evaluate the extent of non-specific target binding
on oligonucleotide microarrays designed for total RNA expression
profiling, a model system of 70-mer probes targeting genes involved
in magnetosome formation (mam genes) of the bacterium Magnetospirillum
gryphiswaldense was established utilizing wild-type strain MSR-1
and an isogenic deletion mutant MSR-1B that lacks all mam genes.
An optimized protocol for the direct chemical labelling of total
cellular RNAs was used. A linear correlation between the amount of
applied RNA and the mean global background intensity was found which
enables a simple and unbiased way of normalizing the data. The results
obtained with the mam deletion mutant MSR-1B revealed a significant
number of false positive signals, even under optimal hybridization
conditions. This indicates a high degree of non-specific binding
in microarray experiments when using longer oligo- or polynucleotides
and RNA as target molecule. Comparative microarray analysis of an
MSR-1B culture and two MSR-1 wild-type cultures grown under different
conditions was done via a three-colour hybridization assay. The additional
information provided by the MSR-1B transcriptome revealed differential
gene expression in the two MSR-1 cultures, which was otherwise undetectable.},
issn = {0723-2020},
keywords = {DNA microarrays, Expression profiling, Direct labelling and detection,
Non-specific hybridization, RNA hybridization},
url = {http://www.sciencedirect.com/science/article/B7GVX-4JTR935-2/2/2dbfef886e94267f5e5d71bc85787ef8}
}
@ARTICLE{Xi2009,
author = {Xi, Dong and Keeler, Benjamin and Zhang, Wentong and Houle, John
D. and Gao, Wen-Jun},
title = {NMDA receptor subunit expression in GABAergic interneurons in the
prefrontal cortex: Application of laser microdissection technique},
journal = {Journal of Neuroscience Methods},
year = {2009},
volume = {176},
pages = {172--181},
number = {2},
month = jan,
abstract = {The selective involvement of a subset of neurons in many psychiatric
disorders, such as gamma-aminobutyric acid (GABA)-ergic interneurons
in schizophrenia, creates a significant need for in-depth analysis
of these cells. Here we introduce a combination of techniques to
examine the relative gene expression of N-methyl-d-aspartic acid
(NMDA) receptor subtypes in GABAergic interneurons from the rat prefrontal
cortex. Neurons were identified by immunostaining, isolated by laser
microdissection and RNA was prepared for reverse transcription polymerase
chain reaction (RT-PCR) and real-time PCR. These experimental procedures
have been described individually; however, we found that this combination
of techniques is powerful for the analysis of gene expression in
individual identified neurons. This approach provides the means to
analyze relevant molecular mechanisms that are involved in the neuropathological
process of a devastating brain disorder.},
issn = {0165-0270},
keywords = {NovaRed, Laser microdissection, Real-time polymerase chain reaction,
Parvalbumin, NMDA receptors, Schizophrenia},
url = {http://www.sciencedirect.com/science/article/B6T04-4TGHN71-1/2/3b7b3190285c6b3edea22cfca55eb18d}
}
@ARTICLE{Xi2008,
author = {Xi, Liqiang and Feber, Andrew and Gupta, Vanita and Wu, Maoxin and
Bergemann, Andrew D. and Landreneau, Rodney J. and Litle, Virginia
R. and Pennathur, Arjun and Luketich, James D. and Godfrey, Tony
E.},
title = {Whole genome exon arrays identify differential expression of alternatively
spliced, cancer-related genes in lung cancer},
journal = {Nucleic Acids Res.},
year = {2008},
volume = {36},
pages = {6535--6547},
number = {20},
month = nov,
abstract = {Alternative processing of pre-mRNA transcripts is a major source of
protein diversity in eukaryotes and has been implicated in several
disease processes including cancer. In this study we have performed
a genome wide analysis of alternative splicing events in lung adenocarcinoma.
We found that 2369 of the 17 800 core Refseq genes appear to have
alternative transcripts that are differentially expressed in lung
adenocarcinoma versus normal. According to their known functions
the largest subset of these genes (30.8%) is believed to be cancer
related. Detailed analysis was performed for several genes using
PCR, quantitative RT-PCR and DNA sequencing. We found overexpression
of ERG variant 2 but not variant 1 in lung tumors and overexpression
of CEACAM1 variant 1 but not variant 2 in lung tumors but not in
breast or colon tumors. We also identified a novel, overexpressed
variant of CDH3 and verified the existence and overexpression of
a novel variant of P16 transcribed from the CDKN2A locus. These findings
demonstrate how analysis of alternative pre-mRNA processing can shed
additional light on differences between tumors and normal tissues
as well as between different tumor types. Such studies may lead to
the development of additional tools for tumor diagnosis, prognosis
and therapy.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/36/20/6535}
}
@ARTICLE{Xia2010,
author = {Xia, J. and Broad, K.D. and Emson, P.C. and Keverne, E.B.},
title = {Epigenetic modification of vomeronasal (V2r) precursor neurons by
histone deacetylation},
journal = {Neuroscience},
year = {2010},
volume = {169},
pages = {1462--1472},
number = {3},
month = sep,
abstract = {Vomeronasal neurons undergo continuous neurogenesis throughout development
and adult life. These neurons originate as stem cells in the apical
zone of the lumen of the vomeronasal organ (VNO) and are described
as nestin-expressing glia-like progenitor cells (Murdoch and Roskams,
2008). They then migrate horizontally along the basal zone where
they differentiate into functional VNO neurons (Kaba et al., 1988).
We harvested progenitor cells from the adult VNO and, after 3-6 months
of invitro culture, these VNO neurons remained in a stable undifferentiated
state expressing nestin, [beta]-tubulin III and vomeronasal type
2 (V2r), but not vomeronasal type 1 (V1r) receptors. Application
of histone-deacetylase inhibitors induced development of a neural
phenotype that expressed V2r receptors, a down-regulation of nestin
expression and no change in any specific genetic markers associated
with glial cells. Treatment with valproic acid induced extensive
changes in gene expression in the axon guidance pathway. The adult
VNO is known to functionally adapt throughout life as a consequence
of changes in both a mouse's physiological status and its social
environment. These pluripotent cultured neurons may provide valuable
insights into how changes in both physiology and environment, exert
epigenetic effects on vomeronasal neurons as they undergo continuous
neurogenesis and development throughout the life of a mouse.},
issn = {0306-4522},
keywords = {mouse, vomeronasal organ, VNO, neurogenesis, epigenetic regulation},
url = {http://www.sciencedirect.com/science/article/B6T0F-50860K7-1/2/682ff15dadf5717dd4f001439a9e1b69}
}
@ARTICLE{Xia2006,
author = {Xia, Qiangwei and Hendrickson, Erik L. and Zhang, Yi and Wang, Tiansong
and Taub, Fred and Moore, Brian C. and Porat, Iris and Whitman, William
B. and Hackett, Murray and Leigh, John A.},
title = {Quantitative Proteomics of the Archaeon Methanococcus maripaludis
Validated by Microarray Analysis and Real Time PCR},
journal = {Mol. Cell. Proteomics},
year = {2006},
volume = {5},
pages = {868--881},
number = {5},
month = may,
abstract = {For the archaeon Methanococcus maripaludis, a fully sequenced and
annotated model species of hydrogenotrophic methanogen, we report
validation of quantitative protein level expression ratios on a proteome-wide
basis. Using an approach based on quantitative multidimensional capillary
HPLC and quadrupole ion trap mass spectrometry, coverage of gene
expression approached that currently achievable with transcription
microarrays. Comprehensive mass spectrometry-based proteomics and
spotted cDNA arrays were used to compare global protein and mRNA
levels in a wild-type (S2) and mutant strain (S40) of M. maripaludis.
Using linear regression with 652 expression ratios generated by both
the proteomic and microarray methods, a product moment correlation
coefficient of 0.24 was observed. The correlation improved to 0.61
if only genes showing significant expression changes were included.
A novel two-stage method of outlier detection was used for the protein
measurements when Dixon's Q-test by itself failed to give satisfactory
results. The log2 transformations of the number of peptides or isotopic
peptide pairs associated with each ORF, divided by the predicted
molecular weight, were found to have moderately positive correlations
with two bioinformatic predictors of gene expression based on codon
bias. We detected peptides derived from 939 proteins or 55% of the
genome coding capacity. Of these, 60 were overexpressed, and 34 were
underexpressed in the mutant. Of the 1722 ORFs encoded in the genome,
1597 or 93% were probed by cDNA arrays. Of these, 50 were more highly
expressed, and 45 showed lower expression levels in the mutant relative
to the wild type. 15 ORFs were shown to be overexpressed by both
methods, and two ORFs were shown to be overexpressed by proteomics
and underexpressed by microarray.},
url = {http://www.mcponline.org/cgi/content/abstract/5/5/868}
}
@ARTICLE{Xia2010a,
author = {Xia, Siqing and Duan, Liang and Song, Yonghui and Li, Jixiang and
Piceno, Yvette M. and Andersen, Gary L. and Alvarez-Cohen, Lisa and
Moreno-Andrade, Ivan and Huang, Chun-Lin and Hermanowicz, Slawomir
W.},
title = {Bacterial Community Structure in Geographically Distributed Biological
Wastewater Treatment Reactors},
journal = {Environmental Science \& Technology},
year = {2010},
volume = {44},
pages = {7391-7396},
number = {19},
doi = {10.1021/es101554m},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/es101554m},
url = {http://pubs.acs.org/doi/abs/10.1021/es101554m}
}
@ARTICLE{Xia2007,
author = {Xia, Weiliang and Mruk, Dolores D and Lee, Will M and Cheng, C Yan},
title = {Unraveling the molecular targets pertinent to junction restructuring
events during spermatogenesis using the Adjudin-induced germ cell
depletion model},
journal = {J. Endocrinol.},
year = {2007},
volume = {192},
pages = {563--583},
number = {3},
month = mar,
abstract = {During spermatogenesis, extensive restructuring takes place at the
Sertoli-Sertoli and Sertoli-germ cell interface, which is regulated
via intriguing interactions among cytokines, proteases, protease
inhibitors, kinases, phosphatases, and transcription factors. This
in turn determines the steady-state levels of integral membrane proteins
at the cell junctions. We sought to further expand these observations
using the Adjudin model. Adjudin is a potential male contraceptive
that targets Sertoli-germ cell adhesion, causing exfoliation of spermatids
and spermatocytes, but not spermatogonia, from the seminiferous epithelium.
This model thus provides the means to identify crucial regulatory
molecules and signaling pathways pertinent to junction restructuring
events during spermatogenesis. In this study, genome-wide expression
profiling of rat testes after treatment with Adjudin at the time
of extensive junction restructuring was performed. Differentially
regulated genes, such as cytokines, proteases, protease inhibitors,
cell junction-associated proteins, and transcription factors pertinent
to junction restructuring were identified. These data were consistent
with earlier findings; however, much new information was obtained
which has been deposited at the Gene Expression Omnibus data repository
website: http://www.ncbi.nih.gov/geo/ with Accession number: GSE5131
. The primary signaling events pertinent to junction restructuring
in the testis induced by Adjudin were also delineated using bioinformatics.
These findings were also consistent with recently published reports.
The identified molecular signatures or targets pertinent to junction
dynamics in the testis as reported herein, many of which have not
been investigated, thus offer a framework upon which the regulation
of junction restructuring events at the Sertoli-Sertoli and Sertoli-germ
cell interface pertinent to spermatogenesis can be further studied.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/192/3/563}
}
@ARTICLE{Xiang2003,
author = {Xiang, Charlie C. and Chen, Mei and Ma, Li and Phan, Quang N. and
Inman, Jason M. and Kozhich, Olga A. and Brownstein, Michael J.},
title = {A new strategy to amplify degraded RNA from small tissue samples
for microarray studies},
journal = {Nucleic Acids Res.},
year = {2003},
volume = {31},
pages = {e53--},
number = {9},
month = may,
abstract = {RNA amplification methods have been used to facilitate making probes
from small tissue samples for microarray studies. Our original amplification
technique relied on driving the first reverse transcription with
oligo(dT) with a T7 RNA polymerase promoter (T7dT) on the 5' end,
and subsequent transcriptions with random 9mers with a T3 RNA polymerase
promoter (T3N9). Thus, initially, poly(A)+ RNA is amplified. This
creates a potential problem: amplifications based on oligo(dT) priming
could be sensitive to RNA degradation; broken mRNA strands should
give rise to shorter cDNAs than those seen when intact templates
are used. This would be especially troublesome when targets other
than those corresponding to the 3' ends of transcripts are printed
on an array. To solve this problem, we elected to prime cDNA synthesis
with T3N9 at the beginning of each amplification cycle. Following
two rounds of amplification, the resulting probes were comparable
to those obtained with our original protocol or the Arcturus RiboAmp
kit. We show below that as many as four rounds of amplification can
be performed reliably. In addition, as predicted, the method works
well with degraded templates.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/31/9/e53}
}
@ARTICLE{Xiang2004,
author = {Xiang, Charlie C. and Mezey, Eva and Chen, Mei and Key, Sharon and
Ma, Li and Brownstein, Michael J.},
title = {Using DSP, a reversible cross-linker, to fix tissue sections for
immunostaining, microdissection and expression profiling},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {e185--},
number = {22},
month = dec,
abstract = {Mammalian organs are typically comprised of several cell populations.
Some (e.g. brain) are very heterogeneous, and this cellular complexity
makes it difficult, if not impossible, to interpret expression profiles
obtained with microarrays. Instruments, such as those manufactured
by Leica or Arcturus, that permit laser capture microdissection of
specific cells or cell groups from tissues were developed to solve
this problem. To take full advantage of these instruments, however,
one must be able to recognize cell populations of interest and, after
they are harvested, to extract intact, unmodified RNA from them.
Here we describe a novel, fast and simple method to fix and immunostain
tissue sections that permits this to be done.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/22/e185}
}
@ARTICLE{Xiang2008,
author = {Xiang, Lianbin and Szebeni, Katalin and Szebeni, Attila and Klimek,
Violetta and Stockmeier, Craig A. and Karolewicz, Beata and Kalbfleisch,
John and Ordway, Gregory A.},
title = {Dopamine receptor gene expression in human amygdaloid nuclei: Elevated
D4 receptor mRNA in major depression},
journal = {Brain Research},
year = {2008},
volume = {1207},
pages = {214--224},
month = may,
abstract = {Previous findings from this laboratory demonstrating changes in dopamine
(DA) transporter and D2 receptors in the amygdaloid complex of subjects
with major depression indicate that disruption of dopamine neurotransmission
to the amygdala may contribute to behavioral symptoms associated
with depression. Quantitative real-time RT-PCR was used to investigate
the regional distribution of gene expression of DA receptors in the
human amygdala. In addition, relative levels of mRNA of DA receptors
in the basal amygdaloid nucleus were measured postmortem in subjects
with major depression and normal control subjects. All five subtypes
of DA receptor mRNA were detected in all amygdaloid subnuclei, although
D1, D2, and D4 receptor mRNAs were more abundant than D3 and D5 mRNAs
by an order of magnitude. The highest level of D1 mRNA was found
in the central nucleus, whereas D2 mRNA was the most abundant in
the basal nucleus. Levels of D4 mRNA were highest in the basal and
central nuclei. In the basal nucleus, amounts of D4, but not D1 or
D2, mRNAs were significantly higher in subjects with major depression
as compared to control subjects. These findings demonstrate that
the D1, D2 and D4 receptors are the major subtypes of DA receptors
in the human amygdala. Elevated DA receptor gene expression in depressive
subjects further implicates altered dopaminergic transmission in
the amygdala in depression.},
issn = {0006-8993},
keywords = {Dopamine receptor, Gene expression, Amygdala, Depression, Major depression,
Real-time PCR, Human brain, Dopamine},
url = {http://www.sciencedirect.com/science/article/B6SYR-4RV17NX-3/2/3f27bc2430918a80d880e2df313dceba}
}
@ARTICLE{Xiang2003a,
author = {Xiang, Ying and Wang, Zhengfu and Murakami, Junko and Plummer, Sarah
and Klein, Eric A. and Carpten, John D. and Trent, Jeffrey M. and
Isaacs, William B. and Casey, Graham and Silverman, Robert H.},
title = {Effects of RNase L Mutations Associated with Prostate Cancer on Apoptosis
Induced by 2',5'-Oligoadenylates},
journal = {Cancer Res.},
year = {2003},
volume = {63},
pages = {6795--6801},
number = {20},
month = oct,
abstract = {The RNASEL gene, a strong candidate for the hereditary prostate cancer
1 allele (HPC1), encodes a single-stranded specific endoribonuclease
involved in the antiviral actions of IFNs. RNase L is activated enzymatically
after binding to unusual 5'-phosphorylated, 2',5'-linked oligoadenylates
(2-5A). Biostable phosphorothioate analogues of 2-5A were synthesized
chemically and used to study the effects of naturally occurring mutations
and polymorphisms in RNASEL. The 2-5A analogues induced RNase L activity
and caused apoptosis in cultures of late-stage, metastatic human
prostate cancer cell lines DU145, PC3, and LNCaP. However, DU145
and PC3 cells were more sensitive to 2-5A than LNCaP cells, which
are heterozygous for an inactivating deletion mutation in RNase L.
The RNase activities of missense variants of human RNase L were compared
after expression in a mouse RNase L-/- cell line. Several variants
(G59S, I97L, I220V, G296V, S322F, Y529C, and D541E) produced similar
levels of RNase L activity as wild-type enzyme. In contrast, the
R462Q variant, previously implicated in up to 13% of unselected prostate
cancer cases, bound 2-5A at wild-type levels but had a 3-fold decrease
in RNase activity. The deficiency in RNase LR462Q activity was correlated
with a reduction in its ability to dimerize into a catalytically
active form. Furthermore, RNase LR462Q was deficient in causing apoptosis
in response to 2-5A consistent with its possible role in prostate
cancer development. Our findings support the notion that RNASEL mutations
and some variants allow tumor cells to escape a potent apoptotic
pathway.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/63/20/6795}
}
@ARTICLE{Xiao2011,
author = {Xiao, C. and Qin, B. and Chen, L. and Liu, H. and Zhu, Y. and Lu,
X.},
title = {Preactivation of the interferon signalling in liver is correlated
with nonresponse to interferon alpha therapy in patients chronically
infected with hepatitis B virus},
journal = {Journal of Viral Hepatitis},
year = {2011},
pages = {no--no},
abstract = {Summary.  Interferon alpha (IFN-α) therapy is widely used to treat
patients with chronic hepatitis B (CHB) but the sustained response
rate is low, and the molecular mechanisms for the ineffectiveness
of IFN-α treatments are not known. We screened differentially expressed
genes between responders (Rs) and nonresponders (NRs) in patients
with CHB treated with IFN-α to explore the molecular basis for treatment
failure. Expression profiling was performed on percutaneous needle
liver biopsy specimens taken before therapy. Gene expression levels
were compared between seven patients who did not respond to therapy
(NR) and six who did respond (R). Gene ontology category and KEGG
pathway were analysed for differentially expressed genes, and the
selected differentially expressed genes were confirmed using real-time
polymerase chain reaction. We identified 3592 genes whose expression
levels differed significantly between all Rs and NRs (PÂ <Â 0.05);
many of these genes are IFN-stimulated genes (ISGs) and immune-related
genes. The ISGs were more highly expressed, while immune-related
genes were inhibited in NRs before IFN-α treatment. Two ISGs (CEB1
and USP18) that are linked in an IFN inhibitory pathway are highly
expressed in NRs, and a potential antiviral gene ISG20 was inhibited
in NRs, suggesting a possible rationale for treatment nonresponse.
Patients who do or do not respond to IFN have different liver gene
expression profiles before IFN-α treatment. Preactivation of the
IFN signalling pathway leading to the increased expression of inhibitory
ISGs and inhibition of immune response in the pretreatment livers
was associated with treatment failure.},
doi = {10.1111/j.1365-2893.2011.01471.x},
issn = {1365-2893},
keywords = {alpha interferon, chronic hepatitis B, differential gene expression,
microarray, no response to treatment},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2893.2011.01471.x}
}
@ARTICLE{XIAO2008,
author = {XIAO, GARY GUISHAN and ZHOU, BING-SEN and SOMLO, GEORGE and PORTNOW,
JANA and JUHASZ, AGNES and UN, FRANK and CHEW, HELEN and GANDARA,
DAVID and YEN, YUN},
title = {Identification of F-box/LLR-repeated Protein 17 as Potential Useful
Biomarker for Breast Cancer Therapy},
journal = {Cancer Genomics Proteomics},
year = {2008},
volume = {5},
pages = {151--160},
number = {3-4},
month = may,
abstract = {Background: The expression and activity of ribonucleotide reductase
(RR) has been associated with resistance to multiple drugs in human
cancer. The use of antisense oligonucleotide drug, GTI-2040, a 20-mer
phosphorothioate oligonucleotide complemented to the human RR M2
subunit mRNA, represents an effective strategy for inhibiting RR.
The increased specificity due to the anti-resistance effect of GTI-2040
may also lead to a more favorable therapeutic outcome. Materials
and Methods: To understand the molecular mechanism underlying RR
inhibition, patients' blood samples were analyzed using multiple
dimensional proteomics technology via matrix-assisted laser desorption
and ionization time-of-flight (MALDI-TOF) mass spectrometry. Results:
A major difference occurred at 5k m/z in the MALDI profile, which
appeared only in the non-responsive group and diminished after GTI-2040
treatment. This specific peptide peak remained at the basal level
in responsive patients. The peak was identified to represent the
F-box/LLR-repeat protein 17 (FBXL17) through nanoelectrospray ionization
liquid chromatography-tandem mass spectrometry (nanoESI LC-MS/MS).
Further characterization revealed that FBXL17/SKP2 directly interacts
with the human RR M2 (RRM2) subunit to promote hRRM2 overexpression
in the breast cancer cell line MCF-7. Conclusion: Validation of this
protein using real-time RT-PCR indicates the F-box protein 17 (FBXL17)
can serve as a therapeutic target and surrogate marker for breast
cancer therapy.},
url = {http://cgp.iiarjournals.org/cgi/content/abstract/5/3-4/151}
}
@ARTICLE{Xiao2007,
author = {Xiao, J. and Gong, S. and LeDoux, M.S.},
title = {Caytaxin deficiency disrupts signaling pathways in cerebellar cortex},
journal = {Neuroscience},
year = {2007},
volume = {144},
pages = {439--461},
number = {2},
month = jan,
abstract = {The genetically dystonic (dt) rat, an autosomal recessive model of
generalized dystonia, harbors an insertional mutation in Atcay. As
a result, dt rats are deficient in Atcay transcript and the neuronally-restricted
protein caytaxin. Previous electrophysiological and biochemical studies
have defined olivocerebellar pathways, particularly the climbing
fiber projection to Purkinje cells, as sites of significant functional
abnormality in dt rats. In normal rats, Atcay transcript is abundantly
expressed in the granular and Purkinje cell layers of cerebellar
cortex. To better understand the consequences of caytaxin deficiency
in cerebellar cortex, differential gene expression was examined in
dt rats and their normal littermates. Data from oligonucleotide microarrays
and quantitative real-time reverse transcriptase-PCR (QRT-PCR) identified
phosphatidylinositol signaling pathways, calcium homeostasis, and
extracellular matrix interactions as domains of cellular dysfunction
in dt rats. In dt rats, genes encoding the corticotropin-releasing
hormone receptor 1 (CRH-R1, Crhr1) and plasma membrane calcium-dependent
ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR.
Immunocytochemical experiments demonstrated that CRH-R1, CRH, and
PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along
with previous electrophysiological and pharmacological studies, our
data indicate that caytaxin plays a critical role in the molecular
response of Purkinje cells to climbing fiber input. Caytaxin may
also contribute to maturational events in cerebellar cortex.},
issn = {0306-4522},
keywords = {dystonia, ataxia, Purkinje cell, climbing fibers, corticotropin-releasing
hormone, microarray},
url = {http://www.sciencedirect.com/science/article/B6T0F-4M9413W-2/2/2b269ef73cbaa223d62e7ee9219ee253}
}
@ARTICLE{Xiao2012,
author = {J. Xiao and G. Kannan and L. Jones-Brando and C. Brannock and I.N.
Krasnova and J.L. Cadet and M. Pletnikov and R.H. Yolken},
title = {Sex-specific changes in gene expression and behavior induced by chronic
Toxoplasma infection in mice},
journal = {Neuroscience},
year = {2012},
pages = { - },
number = {0},
abstract = {There is growing evidence that Toxoplasma gondii modifies the behavior
of its intermediate hosts. We investigated the molecular basis of
these infection-induced behavioral changes, followed by five related
behavioral tests to assess the extent of biological relevance. Gene
expression signatures were generated in the frontal cortex of male
and female mice during the latent stage of infection. We found marked
sex-dependent expression differences in mice. In female mice, Toxoplasma
infection altered the expression of genes involved in the development
of the forebrain, neurogenesis, and sensory and motor coordination
(i.e. downregulation of fatty acid-binding protein 7 and eyes absent
homolog 1, upregulation of semaphorin 7A). In male mice, infection
led mainly to modulation of genes associated with olfactory function
(i.e. downregulation of a number of olfactory receptors and dopamine
receptor D4, upregulation of slit homolog 1). Although infection
appears to affect the olfactory function in male mice, it is the
female but not male mice that exhibited attraction to cat odor. In
contrast, infected male mice showed a deficit in social transmission
of food preference. In contrast to males, infected females displayed
locomotor hyperactivity in open field. General olfaction and sensorimotor
gating were normal in both male and female infection. Our results
indicate that the sex of the host plays a major role in determining
variable brain and behavior changes following Toxoplasma infection.
These observations are consistent with heterogeneity of neuropsychiatric
outcomes of the infection in humans.},
doi = {10.1016/j.neuroscience.2011.12.051},
issn = {0306-4522},
keywords = {Toxoplasma},
url = {http://www.sciencedirect.com/science/article/pii/S0306452211014485}
}
@ARTICLE{Xiao2011b,
author = {Xiao, Junjie and Liang, Dandan and Zhang, Yangyang and Liu, Yi and
Zhang, Hong and Liu, Ying and Li, Li and Liang, Xingqun and Sun,
Yunfu and Chen, Yi-Han},
title = {MicroRNA expression signature in atrial fibrillation with mitral
stenosis},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {655-664},
number = {11},
abstract = {The aim of this study was to investigate the microRNA (miRNA) signature
in atrial fibrillation (AF) with mitral stenosis (MS). miRNA arrays
were used to evaluate the expression signature of the right atrial
appendages of healthy individuals (n = 9), patients with MS and AF
(n = 9) and patients with MS without AF (n = 4). The results were
validated with qRT-PCR analysis. GOmir was used to predict the potential
miRNA targets and to analyze their functions. DIANA-mirPath was used
to incorporate the miRNAs into pathways. miRNA arrays revealed that
136 and 96 miRNAs were expressed at different levels in MS patients
with AF and in MS patients without AF, respectively, compared with
healthy controls. More importantly, 28 miRNAs were expressed differently
in the MS patients with AF compared with the MS patients without
AF; of these miRNAs, miR-1202 was the most dysregulated. The unsupervised
hierarchical clustering analysis based on the 28 differently expressed
miRNAs showed that the heat map of miRNA expression categorized two
well-defined clusters that corresponded to MS with AF and MS without
AF. The qRT-PCR results correlated well with the microarray data.
Bioinformatic analysis indicated the potential miRNA targets and
molecular pathways. This study shows that there is a distinct miRNA
expression signature in AF with MS. The findings may be useful for
the development of therapeutic interventions that are based on rational
target selection in these patients.},
doi = {10.1152/physiolgenomics.00139.2010},
eprint = {http://physiolgenomics.physiology.org/cgi/reprint/43/11/655.pdf},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/11/655}
}
@ARTICLE{Xiao2011d,
author = {Xiao, Lihong and Wang, Hui and Wan, Ping and Kuang, Tingyun and He,
Yikun},
title = {Genome-wide transcriptome analysis of gametophyte development in
Physcomitrella patens},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {177},
number = {1},
abstract = {BACKGROUND:Regulation of gene expression plays a pivotal role in controlling
the development of multicellular plants. To explore the molecular
mechanism of plant developmental-stage transition and cell-fate determination,
a genome-wide analysis was undertaken of sequential developmental
time-points and individual tissue types in the model moss Physcomitrella
patens because of the short life cycle and relative structural simplicity
of this plant.RESULTS:Gene expression was analyzed by digital gene
expression tag profiling of samples taken from P. patens protonema
at 3, 14 and 24 days, and from leafy shoot tissues at 30 days, after
protoplast isolation, and from 14-day-old caulonemal and chloronemal
tissues. In total, 4333 genes were identified as differentially displayed.
Among these genes, 4129 were developmental-stage specific and 423
were preferentially expressed in either chloronemal or caulonemal
tissues. Most of the differentially displayed genes were assigned
to functions in organic substance and energy metabolism or macromolecule
biosynthetic and catabolic processes based on gene ontology descriptions.
In addition, some regulatory genes identified as candidates might
be involved in controlling the developmental-stage transition and
cell differentiation, namely MYB-like, HB-8, AL3, zinc finger family
proteins, bHLH superfamily, GATA superfamily, GATA and bZIP transcription
factors, protein kinases, genes related to protein/amino acid methylation,
and auxin, ethylene, and cytokinin signaling pathways.CONCLUSIONS:These
genes that show highly dynamic changes in expression during development
in P. patens are potential targets for further functional characterization
and evolutionary developmental biology studies.},
url = {http://www.biomedcentral.com/1471-2229/11/177}
}
@ARTICLE{Xiao2008,
author = {Xiao, Peng and Chen, Yuan and Jiang, Hui and Liu, Yao-Zhong and Pan,
Feng and Yang, Tie-Lin and Tang, Zi-Hui and Larsen, Jennifer A and
Lappe, Joan M and Recker, Robert R and Deng, Hong-Wen},
title = {In Vivo Genome-Wide Expression Study on Human Circulating B Cells
Suggests a Novel ESR1 and MAPK3 Network for Postmenopausal Osteoporosis},
journal = {J Bone Miner Res},
year = {2008},
volume = {23},
pages = {644--654},
number = {5},
abstract = {Abstract 10.1359/jbmr.080105.abs Introduction: Osteoporosis is characterized
by low BMD. Studies have shown that B cells may participate in osteoclastogenesis
through expression of osteoclast-related factors, such as RANKL,
transforming growth factor β (TGFB), and osteoprotegerin (OPG).
However, the in vivo significance of B cells in human bone metabolism
and osteoporosis is still largely unknown, particularly at the systematic
gene expression level. Materials and Methods: In this study, Affymetrix
HG-U133A GeneChip arrays were used to identify genes differentially
expressed in B cells between 10 low and 10 high BMD postmenopausal
women. Significance of differential expression was tested by t-test
and adjusted for multiple testing with the Benjamini and Hochberg
(BH) procedure (adjusted p ≤ 0.05). Results: Twenty-nine genes
were downregulated in the low versus high BMD group. These genes
were further analyzed using Ingenuity Pathways Analysis (Ingenuity
Systems). A network involving estrogen receptor 1 (ESR1) and mitogen
activated protein kinase 3 (MAPK3) was identified. Real-time RT-PCR
confirmed differential expression of eight genes, including ESR1,
MAPK3, methyl CpG binding protein 2 (MECP2), proline-serine-threonine
phosphatase interacting protein 1 (PSTPIP1), Scr-like-adaptor (SLA),
serine/threonine kinase 11 (STK11), WNK lysine-deficient protein
kinase 1 (WNK1), and zinc finger protein 446 (ZNF446). Conclusions:
This is the first in vivo genome-wide expression study on human B
cells in relation to osteoporosis. Our results highlight the significance
of B cells in the etiology of osteoporosis and suggest a novel mechanism
for postmenopausal osteoporosis (i.e., that downregulation of ESR1
and MAPK3 in B cells regulates secretion of factors, leading to increased
osteoclastogenesis or decreased osteoblastogenesis).},
issn = {1523-4681},
keywords = {osteoporosis, BMD, microarray, B cells, estrogen receptor 1, mitogen
activated protein kinase 3},
publisher = {John Wiley and Sons and The American Society for Bone and Mineral
Research (ASBMR)},
url = {http://dx.doi.org/10.1359/jbmr.080105}
}
@ARTICLE{Xiao2006,
author = {Xiao, Shen and Anderson, Steven P. and Swanson, Cynthia and Bahnemann,
Rainer and Voss, Kenneth A. and Stauber, Anja J. and Corton, J. Christopher},
title = {Activation of Peroxisome Proliferator-Activated Receptor Alpha Enhances
Apoptosis in the Mouse Liver},
journal = {Toxicol. Sci.},
year = {2006},
volume = {92},
pages = {368--377},
number = {2},
month = aug,
abstract = {Chronic exposure to peroxisome proliferators (PPs) leads to increased
incidence of liver tumors in rodents. Liver tumor induction is thought
to require increased hepatocyte proliferation and suppression of
apoptosis. Transcript profiling showed increased expression of proapoptotic
genes and decreased expression of antiapoptotic genes in the livers
of mice exposed to the PP WY-14,643 (WY). We tested the hypothesis
that prior exposure to WY would increase susceptibility to apoptosis
inducers such as Jo2, an antibody which activates the Fas (Apo-1/CD95)
death pathway. When compared to their untreated counterparts, wild-type
mice pretreated with WY exhibited increased caspase-3 activation
and hepatocyte apoptosis following challenge with Jo2. Livers from
WY-treated peroxisome proliferator-activated receptor alpha (PPAR{alpha})-null
mice were resistant to the effects of Jo2. In the absence of Jo2
and detectable apoptosis, wild-type mice treated with WY exhibited
increases in the activated form of caspase-9. As caspase-9 is a component
of the apoptosome, we examined the expression of upstream effectors
of apoptosome activity including members of the Bcl-2 family. The
levels of the antiapoptotic Mcl-1 transcript and protein were significantly
decreased by PPs. PPAR{alpha}-null mice were also resistant to another
treatment (concanavalin A) that induces hepatocyte apoptosis. These
results (1) indicate that PPAR{alpha} activation increases sensitivity
of the liver to apoptosis and (2) identify a mechanism by which PPAR{alpha}
could serve as a pharmacological target in diseases where apoptosis
is a contributing feature.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/92/2/368}
}
@ARTICLE{Xiao2011a,
author = {Xiao, Shi and Chye, Mee-Len},
title = {Overexpression of Arabidopsis ACBP3 Enhances NPR1-Dependent Plant
Resistance to Pseudomonas syringe pv tomato DC3000},
journal = {Plant Physiology},
year = {2011},
volume = {156},
pages = {2069-2081},
number = {4},
abstract = {ACBP3 is one of six Arabidopsis (Arabidopsis thaliana) genes, designated
ACBP1 to ACBP6, that encode acyl-coenzyme A (CoA)-binding proteins
(ACBPs). These ACBPs bind long-chain acyl-CoA esters and phospholipids
and are involved in diverse cellular functions, including acyl-CoA
homeostasis, development, and stress tolerance. Recombinant ACBP3
binds polyunsaturated acyl-CoA esters and phospholipids in vitro.
Here, we show that ACBP3 plays a role in the plant defense response
to the bacterial pathogen Pseudomonas syringae pv tomato DC3000.
ACBP3 mRNA was up-regulated upon pathogen infection and treatments
using pathogen elicitors and defense-related phytohormones. Transgenic
Arabidopsis ACBP3 overexpressors (ACBP3-OEs) showed constitutive
expression of pathogenesis-related genes (PR1, PR2, and PR5), cell
death, and hydrogen peroxide accumulation in leaves. Consequently,
ACBP3-OEs displayed enhanced resistance to the bacterial pathogen
P. syringae DC3000. In contrast, the acbp3 T-DNA insertional mutant
was more susceptible and exhibited lower PR gene transcript levels
upon infection. Using the ACBP3 OE-1 line in combination with nonexpressor
of PR genes1 (npr1-5) or coronatine-insensitive1 (coi1-2), we concluded
that the enhanced PR gene expression and P. syringae DC3000 resistance
in the ACBP3-OEs are dependent on the NPR1-mediated, but not the
COI1-mediated, signaling pathway. Given that ACBP3-OEs showed greater
susceptibility to infection by the necrotrophic fungus Botrytis cinerea
while the acbp3 mutant was less susceptible, we suggest that ACBP3
plays a role in the plant defense response against biotrophic pathogens
that is distinct from necrotrophic pathogens. ACBP3 function in plant
defense was supported further by bioinformatics data showing up-regulation
of many biotic and abiotic stress-related genes in ACBP3 OE-1 in
comparison with the wild type.},
doi = {10.1104/pp.111.176933},
eprint = {http://www.plantphysiol.org/cgi/reprint/156/4/2069.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/156/4/2069}
}
@ARTICLE{Xiao2010,
author = {Xiao, Shuqi and Mo, Delin and Wang, Qiwei and Jia, Jianyu and Qin,
Limei and Yu, Xiangchun and Niu, Yuna and Zhao, Xiao and Liu, Xiaohong
and Chen, Yaosheng},
title = {Aberrant host immune response induced by highly virulent PRRSV identified
by digital gene expression tag profiling},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {544},
number = {1},
abstract = {BACKGROUND:There was a large scale outbreak of the highly pathogenic
porcine reproductive and respiratory syndrome (PRRS) in China and
Vietnam during 2006 and 2007 that resulted in unusually high morbidity
and mortality among pigs of all ages. The mechanisms underlying the
molecular pathogenesis of the highly virulent PRRS virus (H-PRRSV)
remains unknown. Therefore, the relationship between pulmonary gene
expression profiles after H-PRRSV infection and infection pathology
were analyzed in this study using high-throughput deep sequencing
and histopathology.RESULTS:H-PRRSV infection resulted in severe lung
pathology. The results indicate that aberrant host innate immune
responses to H-PRRSV and induction of an anti-apoptotic state could
be responsible for the aggressive replication and dissemination of
H-PRRSV. Prolific rapid replication of H-PRRSV could have triggered
aberrant sustained expression of pro-inflammatory cytokines and chemokines
leading to a markedly robust inflammatory response compounded by
significant cell death and increased oxidative damage. The end result
was severe tissue damage and high pathogenicity.CONCLUSIONS:The systems
analysis utilized in this study provides a comprehensive basis for
better understanding the pathogenesis of H-PRRSV. Furthermore, it
allows the genetic components involved in H-PRRSV resistance/susceptibility
in swine populations to be identified.},
doi = {10.1186/1471-2164-11-544},
issn = {1471-2164},
pubmedid = {20929578},
url = {http://www.biomedcentral.com/1471-2164/11/544}
}
@ARTICLE{Xiao2005,
author = {Xiao, Xiao Qiu and Grove, Kevin L. and Lau, See Yan and McWeeney,
Shannon and Smith, M. Susan},
title = {Deoxyribonucleic Acid Microarray Analysis of Gene Expression Pattern
in the Arcuate Nucleus/Ventromedial Nucleus of Hypothalamus during
Lactation},
journal = {Endocrinology},
year = {2005},
volume = {146},
pages = {4391--4398},
number = {10},
month = oct,
abstract = {Lactation is characterized by extreme hyperphagia and negative energy
balance resulting from a large energy drain due to milk production
and by a suppression of cyclic ovarian function. Increases in neuropeptide
Y and agouti-related protein and a decrease in proopiomelanocortin
expression in the arcuate nucleus of hypothalamus (ARH) may contribute
to the hyperphagia to maintain energy balance and to the suppression
of LH secretion associated with lactation. However, little is known
about the full extent of neuroendocrine changes in the ARH that may
contribute to the various adaptations occurring during lactation.
To address this issue, we used Affymetrix microarray to acquire a
reliable profile of the lactation-induced transcriptional changes
in micropunches containing the ARH and a portion of the ventromedial
nucleus of the hypothalamus. Using high stringency criteria, 12 genes
were identified as being differentially regulated during lactation,
and an additional 10 genes and three transcribed sequences were identified
using moderate stringency criteria. Changes in neuropeptide Y, enkephalin,
tyrosine hydroxylase, and dynorphin, genes previously shown to be
differentially regulated during lactation, provide validation for
the microarray analysis. New genes identified as being differentially
expressed include those related to neurotransmission, growth factors,
signal transduction, and structure remodeling. These data identify
new genes in ARH/ventromedial nucleus of the hypothalamus that may
play an important role in the adaptations of lactation related to
hyperphagia, milk production, and the suppression of cyclic reproductive
function and may contribute to elucidating a framework for integrating
changes in energy intake with the regulation of reproductive function
during lactation.},
url = {http://endo.endojournals.org/cgi/content/abstract/146/10/4391}
}
@ARTICLE{Xiao2011c,
author = {Xiao, Ying and Cui, Jue and Shi, Yonghui and Le, Guowei},
title = {Lipoic acid increases the expression of genes involved in bone formation
in mice fed a high-fat diet},
journal = {Nutrition Research},
year = {2011},
volume = {31},
pages = {309--317},
number = {4},
month = apr,
abstract = {Antioxidant lipoic acid (LA) has been reported to have a potential
prophylactic effect on bone loss induced by high-fat diet (HFD).
The aim of this work was to examine the hypothesis that LA decreases
bone resorption-related gene expression and increases bone formation-related
gene expression in HFD-fed mice, preventing a shift in the bone metabolism
balance toward resorption. Male C57BL/6 mice were fed a normal diet,
HFD, or HFD plus 0.1% LA for 12 weeks. The bone metabolism-related
genes differentially expressed between mice fed HFD and those fed
HFD supplemented with LA were identified through complementary DNA
microarray. The supplemental LA significantly increased bone mineral
density and bone antioxidant capacity in mice fed HFD (P < .05).
Compared with the HFD-fed mice, LA induced the decreased expression
of genes associated with bone resorption, such as Mmp9 (1.9-fold)
and Ctsk (2.3-fold), and increased those genes associated with bone
formation, such as Col1a1 (1.3-fold) and Alp1 (1.5-fold). Furthermore,
LA upregulated many genes involved in the Igf signaling pathway,
such as Igf-1 (increased 1.7-fold), and downregulated genes involved
in the p53 apoptotic pathway, such as p53 (decreased 2.3-fold), thus
attenuating the HFD-induced inhibition of bone formation. Lipoic
acid induced upregulation of Il12a (2.1-fold) and downregulation
of Tgfbr1 (4.3-fold) and Il17a (11.3-fold), which may reduce bone
resorption. In summary, LA supplementation during HFD could affect
bone density, altering gene expression.},
issn = {0271-5317},
keywords = {Antioxidants, Lipoic acid, Bone, High-fat diet, Gene expression, cDNA
microarray, Mice},
url = {http://www.sciencedirect.com/science/article/pii/S0271531711000510}
}
@ARTICLE{Xiao2007a,
author = {Xiao, Yin and Fu, Huihua and Prasadam, Indira and Yang, Yaw-Ching
and Hollinger, Jeffrey O.},
title = {Gene expression profiling of bone marrow stromal cells from juvenile,
adult, aged and osteoporotic rats: With an emphasis on osteoporosis},
journal = {Bone},
year = {2007},
volume = {40},
pages = {700--715},
number = {3},
month = mar,
abstract = {Purpose: Osteoporosis is a multi-factorial, age-related disease with
a complex etiology and mode of regulation involving a large numbers
of genes. To better understand the possible relationships among genes,
we fingerprinted genes in a rat model induced by ovariectomy to determine
differences among osteoporotic, non-osteoporotic, aged and juvenile
rats.Methods: We applied genome wide cDNA microarray technology to
analyze genes expressed in bone marrow mesenchymal stromal cells
(BMSC) and compared non-osteoporotic adult vs. osteoporotic, non-osteoporotic
adult vs. aged, and non-osteoporotic adult vs. juvenile. Rigorous
statistical analysis of functional annotation (EASE program) identified
over-represented biological and molecular functions with significant
group wide changes (p <= 0.05). Some of the expressed genes were
further confirmed by quantitative RT-PCR (reverse transcription-polymerase
chain reaction).Results: Differences in gene expression were observed
by identifying transcripts selected by t-test that were consistently
changed by a minimum of two-fold. There were 195 transcripts that
showed an increased expression and 109 transcripts that showed decreased
expression relative to the osteoporotic condition. Of these, 75%
transcripts were unknown gene products or ESTs (expressed sequence
tag). A number of genes found in the aged and juvenile groups were
not present in the osteoporotic rats. Functional clustering of the
genes using the EASE bioinformatics program revealed that transcripts
in osteoporosis were associated with signal transduction, lipid metabolism,
protein metabolism, ionic and protein transport, neuropeptide and
G protein signaling pathways. Although some of the genes have previously
been shown to play a key role in osteoporosis, several genes were
uniquely identified in this study and likely play a role in developing
aged related osteoporosis that could have compelling implications
in the development of new diagnostic strategies and therapeutics
for osteoporosis.Conclusions: These data suggest that osteoporosis
is associated with changes of multiple novel gene expression and
that numerous pathways could play important roles in osteoporosis
pathogenesis.},
issn = {8756-3282},
keywords = {Osteoporosis, Bone marrow stromal cell, cDNA microarray},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4MJJC8J-1/2/d24f90ef5d2f468129964e6867f47cf7}
}
@ARTICLE{Xie2011d,
author = {Xie, Chenghui and Kang, Jie and Burris, Ramona and Ferguson, Matthew
E. and Schauss, Alexander G. and Nagarajan, Shanmugam and Wu, Xianli},
title = {Açaí juice attenuates atherosclerosis in ApoE deficient mice through
antioxidant and anti-inflammatory activities},
journal = {Atherosclerosis},
year = {2011},
volume = {216},
pages = {327 - 333},
abstract = {Objective Açaí fruit pulp has received much attention because of its
high antioxidant capacity and potential anti-inflammatory effects.
In this study, athero-protective effects of açaí juice were investigated
in apolipoprotein E deficient (apoE-/-) mice.Methods and results
ApoE-/- mice were fed AIN-93G diet (CD) or CD formulated to contain
5% freeze-dried açaí juice powder (AJ) for 20 weeks. The mean lesion
areas in the aorta for apoE-/- mice fed AJ were 58% less (P < 0.001)
compared to that for CD fed mice. HDL-cholesterol was higher in AJ
fed mice. Biomarkers of lipid peroxidation, including F2-isoprostanes
and isomers of hydroxyoctadecadienoic acids and hydroxyeicosatetraenoic
acids were significantly lower in serum and in liver of AJ fed mice.
Expression of the two antioxidant enzyme genes, Gpx3 and Gsr, were
significantly up-regulated in the aorta from AJ fed mice. The activity
of GPX, GSR and PON1 increased in serum and/or liver of mice fed
AJ. In the second experiment, ApoE-/- mice were fed CD or AJ for
5 weeks. Serum levels, gene expression and protein levels of the
two proinflammatory cytokines TNF-[alpha] and IL-6 in the resident
macrophages with or without LPS stimulation were lower in mice fed
AJ. SEAP reporter assay determined that AJ reduced NF-[kappa]B activation.Conclusion
Reducing lipid peroxidation through boosting antioxidant enzymes
and inhibiting pro-inflammatory cytokine production are proposed
as major underlying mechanisms for the athero-protective effects
of the açaí juice tested in these experimental in vivo models.},
issn = {0021-9150},
keywords = {Açaí, Euterpe oleracea Mart., Inflammation, Antioxidant enzyme, apoE-deficient
mice, Atherosclerosis, Cytokine},
url = {http://www.sciencedirect.com/science/article/pii/S0021915011001997}
}
@ARTICLE{Xie2011b,
author = {Xie, Hui and Sun, Mei and Liao, Xiao-Bo and Yuan, Ling-Qing and Sheng,
Zhi-Feng and Meng, Ji-Cai and Wang, Dan and Yu, Zhi-Yong and Zhang,
Lei-Yi and Zhou, Hou-De and Luo, Xiang-Hang and Li, Hui and Wu, Xian-Ping
and Wei, Qi-You and Tang, Si-Yuan and Wang, Zhao-Yi and Liao, Er-Yuan},
title = {Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol
in postmenopausal women},
journal = {Journal of Bone and Mineral Research},
year = {2011},
volume = {26},
pages = {156--168},
number = {1},
abstract = {Abstract Recently, a membrane-based estrogen receptor (ER), ER-α36,
was identified and cloned that transduces membrane-initiated estrogen
signaling such as activation of the mitogen-activated protein kinase/extracellular
signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show
that the postmenopausal level of estradiol (E2) induces mitogenic,
antiapoptotic, and antiosteogenic effects and proapoptotic effects
in postmenopausal osteoblasts and osteoclasts with high levels of
ER-α36 expression, respectively. We also found that ER-α36 mediated
the effects of postmenopausal-level E2 on proliferation, apoptosis,
and differentiation of osteoblasts through transient activation of
the MAPK/ERK pathway, whereas ER-α36-mediated postmenopausal-level
E2 induces apoptosis of osteoclasts through prolonged activation
of the MAPK/ERK pathway with the involvement of reactive oxygen species.
We also show that the levels of ER-α36 expression in bone are positively
associated with bone mineral density but negatively associated with
bone biochemical markers in postmenopausal women. Thus the higher
levels of ER-α36 expression are required for preserving bone mass
in postmenopausal and menopausal women who become osteoporotic if
ER-α36-mediated activities are dysregulated. © 2011 American Society
for Bone and Mineral Research.},
doi = {10.1002/jbmr.169},
issn = {1523-4681},
keywords = {ESTROGEN RECEPTOR α36, OSTEOBLAST, OSTEOCLAST, APOPTOSIS, BONE MINERAL
DENSITY},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jbmr.169}
}
@ARTICLE{Xie2011,
author = {Xie, Qian and Bradley, Robert and Kang, Liang and Koeman, Julie and
Ascierto, Maria Libera and Worschech, Andrea and De Giorgi, Valeria
and Wang, Ena and Kefene, Lisa and Su, Yanli and Essenburg, Curt
and Kaufman, Dafna W. and DeKoning, Tom and Enter, Mark A. and O'Rourke,
Timothy J. and Marincola, Francesco M. and Vande Woude, George F.},
title = {Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity
to MET inhibition in glioblastoma},
journal = {PNAS},
year = {2011},
pages = {1119059109},
abstract = {Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical
development against several types of cancer, including glioblastoma,
it is important to identify predictive markers that indicate patient
subgroups suitable for such therapies. We investigated in vivo glioblastoma
models characterized by hepatocyte growth factor (HGF) autocrine
or paracrine activation, or by MET or EGFR amplification, for their
susceptibility to MET inhibitors. HGF autocrine expression correlated
with high phospho-MET levels in HGF autocrine cell lines, and these
lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine
environment may enhance glioblastoma growth in vivo but did not indicate
sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity
to EGFR inhibition, but in the same tumor, increased copies of MET
from gains of chromosome 7 did not result in increased MET activity
and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine
glioblastoma bears an activated MET signaling pathway that may predict
sensitivity to MET inhibitors. Moreover, serum HGF levels may serve
as a biomarker for the presence of autocrine tumors and their responsiveness
to MET therapeutics.},
doi = {10.1073/pnas.1119059109},
eprint = {http://www.pnas.org/cgi/reprint/1119059109v1.pdf},
url = {http://www.pnas.org/cgi/content/abstract/1119059109v1}
}
@ARTICLE{Xie2011a,
author = {Xie, Ran and Chung, Joon-Yong and Ylaya, Kris and Williams, Reginald
L. and Guerrero, Natalie and Nakatsuka, Nathan and Badie, Cortessia
and Hewitt, Stephen M.},
title = {Factors Influencing the Degradation of Archival Formalin-Fixed Paraffin-Embedded
Tissue Sections},
journal = {Journal of Histochemistry \& Cytochemistry},
year = {2011},
volume = {59},
pages = {356--365},
number = {4},
month = apr,
abstract = {The loss of antigenicity in archival formalin-fixed paraffin-embedded
(FFPE) tissue sections negatively affects both diagnostic histopathology
and advanced molecular studies. The mechanisms underlying antigenicity
loss in FFPE tissues remain unclear. The authors hypothesize that
water is a crucial contributor to protein degradation and decrement
of immunoreactivity in FFPE tissues. To test their hypothesis, they
examined fixation time, processing time, and humidity of storage
environment on protein integrity and antigenicity by immunohistochemistry,
Western blotting, and protein extraction. This study revealed that
inadequate tissue processing, resulting in retention of endogenous
water in tissue sections, results in antigen degradation. Exposure
to high humidity during storage results in significant protein degradation
and reduced immunoreactivity, and the effects of storage humidity
are temperature dependent. Slides stored under vacuum with desiccant
do not protect against the effects of residual water from inadequate
tissue processing. These results support that the presence of water,
both endogenously and exogenously, plays a central role in antigenicity
loss. Optimal tissue processing is essential. The parameters of optimal
storage of unstained slides remain to be defined, as they are directly
affected by preanalytic variables. Nevertheless, minimization of
exposure to water is required for antigen preservation in FFPE tissue
sections. This article contains online supplemental material at http://www.jhc.org.
Please visit this article online to view these materials.},
comment = {10.1369/0022155411398488},
url = {http://jhc.sagepub.com/cgi/content/abstract/59/4/356}
}
@ARTICLE{Xie2011c,
author = {Xie, Ting and Liang, Jiurong and Guo, Rishu and Liu, Ningshan and
Noble, Paul W. and Jiang, Dianhua},
title = {Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis
identifies multiple sites of molecular regulation},
journal = {Physiol Genomics},
year = {2011},
volume = {43},
pages = {479--487},
number = {9},
month = may,
abstract = {The molecular mechanisms of lung injury and fibrosis are incompletely
understood. MicroRNAs (miRNAs) are crucial biological regulators
that act by suppressing their target genes and are involved in a
variety of pathophysiological processes. To gain insight into miRNAs
in the regulation of lung fibrosis, total RNA was isolated from mouse
lungs harvested at different days after bleomycin treatment, and
miRNA array with 1,810 miRNA probes was performed thereafter. MiRNAs
expressed in lungs with bleomycin treatment at different time points
were compared with miRNAs expressed in lungs without bleomycin treatment,
resulting in 161 miRNAs differentially expressed. Furthermore, miRNA
expression patterns regulated in initial and late periods after bleomycin
were identified. Target genes were predicted in silico for differentially
expressed miRNAs, including let-7f, let-7g, miR-196b, miR-16, miR-195,
miR-25, miR-144, miR-351, miR-153, miR-468, miR-449b, miR-361, miR-700,
miR-704, miR-717, miR-10a, miR-211, miR-34a, miR-367, and miR-21.
Target genes were then cross-referenced to the molecular pathways,
suggesting that the differentially expressed miRNAs regulate apoptosis,
Wnt, Toll-like receptor, and TGF-{beta} signaling. Our study demonstrated
a relative abundance of miRNA levels in bleomycin-induced lung fibrosis.
The miRNAs and their potential target genes identified may contribute
to the understanding of the complex transcriptional program of lung
fibrosis.},
comment = {10.1152/physiolgenomics.00222.2010},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/43/9/479}
}
@ARTICLE{Xie2010a,
author = {Xie, Yi and Kang, Mei and Tao, Chuanmin and Guo, Liang and Ye, Yuanxin
and Fan, Hong},
title = {Molecular Epidemiology of an Outbreak of Multidrug-Resistant Acinetobacter
baumannii in an Intensive Care Unit of Victims of the Wenchuan Earthquake},
journal = {Lab Med},
year = {2010},
volume = {41},
pages = {292--295},
number = {5},
month = may,
abstract = {ObjectiveDuring a 2-week period after the Wenchuan earthquake, 7 earthquake
patients suffering from invasive infections caused by multidrug-resistant
(MDR) Acinetobacter baumannii (A. baumannii) were identified in the
traumatic intensive care unit (ICU) of our hospital. This study is
to characterize the epidemiological aspects of this outbreak. MethodsA.
baumannii strains were identified and tested for antibiotic susceptibility
by automated instruments. The clonal relatedness was determined using
the DiversiLab Microbial Typing System. ResultsSeventeen A. baumannii
isolates were isolated, including 11 from earthquake victims and
6 from the environment. Three different antibiogram profiles were
present among the 17 isolates. Molecular analysis was performed and
defined the following 5 different clusters: I (n=6), II (n=8), and
III to V (1 isolate each). ConclusionA. baumannii is 1 of the most
important pathogens with a high incidence of nosocomial infection.
The DiversiLab System is a useful tool to identify an outbreak of
a nasocomial infection caused by genetically-related pathogens.},
url = {http://labmed.ascpjournals.org/cgi/content/abstract/41/5/292}
}
@ARTICLE{Xie2010c,
author = {Xie, Ying and Todd, Nevins W. and Liu, Zhenqiu and Zhan, Min and
Fang, HongBin and Peng, Hong and Alattar, Mohammed and Deepak, Janaki
and Stass, Sanford A. and Jiang, Feng},
title = {Altered miRNA expression in sputum for diagnosis of non-small cell
lung cancer},
journal = {Lung Cancer},
year = {2010},
volume = {67},
pages = {170--176},
number = {2},
month = feb,
abstract = {Analysis of molecular genetic markers in biological fluids has been
proposed as a useful tool for cancer diagnosis. MicroRNAs (miRNAs)
are small regulatory RNAs that are frequently dysregulated in lung
cancer and have shown promise as tissue-based markers for its prognostication.
The aim of this study was to determine whether aberrant miRNA expression
can be used as a marker in sputum specimen for the diagnosis of non-small
cell lung cancer (NSCLC). Experimental design: expressions of mature
miRNAs, mir-21 and mir-155, were examined by real-time reverse transcription
polymerase chain reaction (RT-PCR) and normalized to that of control
miRNA, U6B, in sputum of 23 patients with NSCLC and 17 cancer-free
subjects. The data was compared with conventional sputum cytology
for the diagnosis of lung cancer. All endogenous miRNAs were present
in sputum in a remarkably stable form and sensitively and specifically
detected by real-time RT-PCR. Mir-21 expression in the sputum specimens
was significantly higher in cancer patients (76.32 ± 9.79) than cancer-free
individuals (62.24 ± 3.82) (P < 0.0001). Furthermore, overexpression
of mir-21 showed highly discriminative receiver-operator characteristic
(ROC) curve profile, clearly distinguishing cancer patients from
cancer-free subjects with areas under the ROC curve at 0.902 ± 0.054.
Detection of mir-21 expression produced 69.66% sensitivity and 100.00%
specificity in diagnosis of lung cancer, as compared with 47.82%
sensitivity and 100.00% specificity by sputum cytology. The measurement
of altered miRNA expression in sputum could be a useful noninvasive
approach for the diagnosis of lung cancer.},
issn = {0169-5002},
keywords = {MicroRNA, Sputum, Lung cancer, Real-time RT-PCR, Diagnosis},
url = {http://www.sciencedirect.com/science/article/B6T9C-4W91CGH-1/2/ce9d237194cf7e218d0309a0a8186cf2}
}
@ARTICLE{Xie2010,
author = {Xie, Zidian and Li, Dongmei and Wang, Lijun and Sack, Fred D. and
Grotewold, Erich},
title = {Role of the stomatal development regulators FLP/MYB88 in abiotic
stress responses},
journal = {The Plant Journal},
year = {2010},
volume = {64},
pages = {731--739},
number = {5},
abstract = {Summary Stomata are vital for the adaptation of plants to abiotic
stress, and in turn stomatal density is modulated by environmental
factors. Less clear, however, is whether regulators of stomatal development
themselves participate in the sensing or response of stomata to abiotic
stress. FOUR LIPS (FLP) and its paralog MYB88 encode MYB proteins
that establish stomatal patterning by permitting only a single symmetric
division before stomata differentiate. Hence, flp-1 myb88 double
mutants have an excess of stomata, which are often misplaced in direct
contact. Here, we investigate the consequences of loss of FLP/MYB88
function on the ability of Arabidopsis plants to respond to abiotic
stress. While flp-1 myb88 double mutants are viable and display no
obvious aerial phenotypes under normal greenhouse growth conditions,
we show that flp-1 myb88 plants are significantly more susceptible
to drought and high salt, and have increased rates of water loss.
To determine whether flp-1 myb88 plants are already challenged under
normal growth conditions, we compared genome-wide transcript levels
between flp-1 myb88 and wild-type green tissues. Unexpectedly, uninduced
flp-1 myb88 plants showed a reduced accumulation of many typical
abiotic stress gene transcripts. Moreover, the induction of many
of these stress genes under high-salt conditions was significantly
lower in flp-1 myb88 plants. Our results provide evidence for a new
function of FLP/MYB88 in sensing and/or transducing abiotic stress,
which is severely compromised in flp-1 myb88 mutants.},
doi = {10.1111/j.1365-313X.2010.04364.x},
issn = {1365-313X},
keywords = {FLP/MYB88, MYB, salt stress, abscisic acid, Arabidopsis, stomata},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04364.x}
}
@ARTICLE{Xie2010b,
author = {Xie, Zuoquan and Li, Houkai and Wang, Ke and Lin, Jingchao and Wang,
Qi and Zhao, Guoping and Jia, Wei and Zhang, Qinghua},
title = {Analysis of transcriptome and metabolome profiles alterations in
fatty liver induced by high-fat diet in rat},
journal = {Metabolism},
year = {2010},
volume = {59},
pages = {554--560},
number = {4},
month = apr,
abstract = {Excessive energy intake greatly contributes to the development of
nonalcoholic fatty liver disease (NAFLD) in modern society. To better
understand the comprehensive mechanisms of NAFLD development, we
investigated the metabolic alterations of rats with NAFLD induced
by high-fat diet (HFD). Male Wistar rats were fed a HFD or standard
chow for control. After 16 weeks, rat serum was collected for biochemical
measurement. The rats' livers were resected and subjected to histology
inspection and gene expression analysis with complementary DNA microarray
and metabolic analysis with gas chromatography-mass spectroscopy.
In HFD rats, the serum cholesterol, triglycerides, glucose, and insulin
contents were increased; and the total cholesterol and triglycerides
in the livers were also significantly increased. Complementary DNA
microarray analysis revealed that 130 genes were regulated by HFD.
Together with real-time reverse transcriptase polymerase chain reaction,
lipid metabolism regulatory members like sterol regulatory element
binding factor 1 and stearoyl-coenzyme A desaturase 1 had up-regulation,
whereas others like peroxisome proliferator-activated receptor, carnitine
palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl-coenzyme A
reductase had repressed expression, in HFD rat livers. Metabolomic
analysis showed that tetradecanoic acid, hexadecanoic acid, and oleic
acid had elevation and arachidonic acid and eicosapentaenoic acid
had decreased content in HFD rat livers. Amino acids including glycine,
alanine, aspartic acid, glutamic acid, and proline contents were
decreased. The integrative results from transcriptomic and metabolomic
studies revealed that, in HFD rat livers, fatty acid utilization
through [beta]-oxidation was inhibited and lipogenesis was enhanced.
These observations facilitated our understanding of the pathways
involved in the development of NAFLD induced by HFD.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/B6WN4-4XP8TDT-2/2/8d86360db1f31d6103830eb8904c2138}
}
@ARTICLE{Xin2004,
author = {Xin, Hong and Bernal, Alejandro and Amato, Frank A. and Pinhasov,
Albert and Kauffman, Jack and Brenneman, Douglas E. and Derian, Claudia
K. and Andrade-Gordon, Patricia and Plata-Salaman, Carlos R. and
Ilyin, Sergey E.},
title = {High-Throughput siRNA-Based Functional Target Validation},
journal = {J Biomol Screen},
year = {2004},
volume = {9},
pages = {286--293},
number = {4},
month = jun,
abstract = {The drug discovery process pursued by major pharmaceutical companies
for many years starts with target identification followed by high-throughput
screening (HTS) with the goal of identifying lead compounds. To accomplish
this goal, significant resources are invested into automation of
the screening process or HTS. Robotic systems capable of handling
thousands of data points per day are implemented across the pharmaceutical
sector. Many of these systems are amenable to handling cell-based
screening protocols as well. On the other hand, as companies strive
to develop innovative products based on novel mechanisms of action(s),
one of the current bottlenecks of the industry is the target validation
process. Traditionally, bioinformatics and HTS groups operate separately
at different stages of the drug discovery process. The authors describe
the convergence and integration of HTS and bioinformatics to perform
high-throughput target functional identification and validation.
As an example of this approach, they initiated a project with a functional
cell-based screen for a biological process of interest using libraries
of small interfering RNA (siRNA) molecules. In this protocol, siRNAs
function as potent gene-specific inhibitors. siRNA-mediated knockdown
of the target genes is confirmed by TaqMan analysis, and genes with
impacts on biological functions of interest are selected for further
analysis. Once the genes are confirmed and further validated, they
may be used for HTS to yield lead compounds.},
url = {http://jbx.sagepub.com/cgi/content/abstract/9/4/286}
}
@ARTICLE{Xinarianos2006,
author = {Xinarianos, George and McRonald, Fiona E. and Risk, Janet M. and
Bowers, Naomi L. and Nikolaidis, Georgios and Field, John K. and
Liloglou, Triantafillos},
title = {Frequent genetic and epigenetic abnormalities contribute to the deregulation
of cytoglobin in non-small cell lung cancer},
journal = {Hum. Mol. Genet.},
year = {2006},
volume = {15},
pages = {2038--2044},
number = {13},
month = jul,
abstract = {Lung cancer demonstrates the highest mortality in the UK. Previous
studies have implicated allelic loss at chromosome 17q in the development
of non-small cell lung carcinoma (NSCLC), and a number of known and
putative tumour-suppressor genes reside within this region. One candidate
tumour-suppressor gene is cytoglobin (CYGB), which is contained entirely
within the 42.5 kb tylosis with oesophageal cancer (TOC) minimal
region. CYGB abnormalities have been demonstrated only in sporadic
head and neck cancers. In this study, we investigated the expression,
promoter methylation and allelic imbalance status of this gene in
52 paired (normal/tumour) surgically excised lung tissue samples
from patients with NSCLC. CYGB expression in tumour tissue was significantly
reduced compared with corresponding adjacent normal in 54% of the
examined cases (paired t-test, P<0.001). The CYGB promoter was shown
by pyrosequencing to be significantly hypermethylated [2-fold increase
of methylation index (MtI) in tumours] in 25/52 (48%) tumour samples
compared with normal samples. MtI of the CYGB promoter was associated
with CYGB mRNA expression (linear regression analysis, P=0.009),
suggesting a primary role for the epigenetic events in CYGB silencing.
In addition, frequent LOH was detected at the locus 17q25 in 32/48
(67%) tumours examined. It is of note that the loss of expression
intensified when both LOH and hypermethylation coincided in samples
(Mann-Whitney, P=0.049). These findings provide the first evidence
to suggest the implication of CYGB in the pathogenesis of NSCLCs.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/15/13/2038}
}
@ARTICLE{Xinarianos2006a,
author = {Xinarianos, George and Panutsopulos, Dimitrios and Fielding, Patricia
and Gosney, John R. and Spandidos, Demetrios A. and Liloglou, Triantafillos
and Field, John K.},
title = {Loss of CACNA2D2 expression in non-small cell lung cancer},
journal = {AACR Meeting Abstracts},
year = {2006},
volume = {2006},
pages = {986-c--},
number = {1},
month = apr,
abstract = {Genetic events at chromosome 3p have been implicated in the development
of non-small cell lung carcinoma (NSCLC). A number of known and putative
tumour-suppressor genes reside within this region, including CACNA2D2.
This is a candidate tumour-suppressor gene which is located at 3p21.
Although CACNA2D2expression has previously been analysed in some
lung cancer cell lines, its role in the development of primary NSCLC
has yet to be elucidated. In this study, expression of the CACNA2D2
gene was investigated in 55 paired (normal/tumour), surgically excised
lung tissue samples from patients with NSCLC. Promoter methylation
status and loss of heterozygosity (LOH) at 3p were investigated in
48 of these samples. expression levels of CACNA2D2were studied using
comparative multiplex RT-PCR and subsequent analysis on an Agilent
Bioanalyser. We have also developed a pyrosequencing assay on bisulphite
treated DNA to examine the methylation status of part of the CACNA2D2promoter.
Analysis was carried out on a PSQ96MA System. LOH was carried out
using fluorescent microsatellite markers at three loci (D3S1289,
D3S1300, and D3S1263) and analysis on a 377 ABI automated sequencer.
CACNA2D2 was underexpressed in 49 (89%) of 55 lung tumours compared
to their adjacent normal tissue counterparts. The CACNA2D2 promoter
was hypermethylated, in at least one CpG site out of four examined,
in 2 (4%) of 48 samples investigated. LOH was detected in 26 (67%)
of 39, 26 (60%) of 43 and 23 (70%) of 33 informative cases in markers
D3S1289, D3S1263 and D3S1300 respectively. Loss of CACNA2D2 expression
was more frequent in tumours with positive than tumours with negative
nodes (Fisher's exact, p=0.05). There was no association between
CACNA2D2 expression and histology, T stage, M status and differentiation.
These data demonstrate that loss of CACNA2D2 expression is a very
frequent event in the development of NSCLC. Promoter hypermethylation
of CACNA2D2is rare and doesn't appear as a major mechanism accounting
for this loss of expression. Other intrinsic or extrinsic factors
may contribute to the transcriptional silencing of CACNA2D2 in the
molecular pathogenesis of NSCLC. This research was funded by the
Roy Castle Foundation UK.},
url = {http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/986-c}
}
@ARTICLE{Xing2005,
author = {Xing, Weirong and Baylink, David and Kesavan, Chandrasekhar and Hu,
Yan and Kapoor, Susanna and Chadwick, Robert B. and Mohan, Subburaman},
title = {Global gene expression analysis in the bones reveals involvement
of several novel genes and pathways in mediating an anabolic response
of mechanical loading in mice},
journal = {J. Cell. Biochem.},
year = {2005},
volume = {96},
pages = {1049--1060},
number = {5},
abstract = {Abstract 10.1002/jcb.20606.abs To identify the genes and signal pathways
responsible for mechanical loading-induced bone formation, we evaluated
differential gene expression on a global basis in the tibias of C57BL/6J
(B6) mice after four days of four-point bending. We applied mechanical
loads to the right tibias of the B6 mice at 9 N, 2 Hz for 36 cycles
per day, with the left tibias used as unloaded controls. RNA from
the tibias was harvested 24 h after last stimulation and subjected
to microarray. Of the 20,280 transcripts hybridized to the array,
346 were differentially expressed in the loaded bones compared to
the controls. The validity of the microarray data was established
with the increased expression of bone-related genes such as pleiotrophin,
osteoglycin, and legumain upon four-point bending and confirmation
of increased expression of selected genes by real-time PCR. The list
of differentially expressed genes includes genes involved in cell
growth, differentiation, adhesion, proteolysis, as well as signaling
molecules of receptors for growth factors, integrin, Ephrin B2, endothelin,
and adhesion G protein coupled receptor. Pathway analyses suggested
that 28 out of the 346 genes exhibited a direct biological association.
Among the biological network, fibronectin and pleitrophin function
as important signaling molecules in regulating periosteal bone formation
and resorption in response to four-point bending. Furthermore, some
expressed sequence tags (ESTs) with no prior known function have
been identified as potential mediators of mechanotransduction signaling
pathways. Further studies on these previously unknown genes will
improve our understanding of the molecular pathways and mechanisms
involved in bone's response to mechanical stress. © 2005 Wiley-Liss,
Inc.},
issn = {1097-4644},
keywords = {osteogenesis, microarray, mechanical loading, bone, gene expression},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jcb.20606}
}
@ARTICLE{Xiong2010,
author = {Xiong, Jie and Feng, Lifang and Yuan, Dongxia and Fu, Chengjie and
Miao, Wei},
title = {Genome-wide identification and evolution of ATP-binding cassette
transporters in the ciliate Tetrahymena thermophila: A case of functional
divergence in a multigene family},
journal = {BMC Evolutionary Biology},
year = {2010},
volume = {10},
pages = {330},
number = {1},
abstract = {BACKGROUND:In eukaryotes, ABC transporters that utilize the energy
of ATP hydrolysis to expel cellular substrates into the environment
are responsible for most of the efflux from cells. Many members of
the superfamily of ABC transporters have been linked with resistance
to multiple drugs or toxins. Owing to their medical and toxicological
importance, members of the ABC superfamily have been studied in several
model organisms and warrant examination in newly sequenced genomes.
RESULTS:A total of 165 ABC transporter genes, constituting a highly
expanded superfamily relative to its size in other eukaryotes, were
identified in the macronuclear genome of the ciliate Tetrahymena
thermophila. Based on ortholog comparisons, phylogenetic topologies
and intron characterizations, each highly expanded ABC transporter
family of T. thermophila was classified into several distinct groups,
and hypotheses about their evolutionary relationships are presented.
A comprehensive microarray analysis revealed divergent expression
patterns among the members of the ABC transporter superfamily during
different states of physiology and development. Many of the relatively
recently formed duplicate pairs within individual ABC transporter
families exhibit significantly different expression patterns. Further
analysis showed that multiple mechanisms have led to functional divergence
that is responsible for the preservation of duplicated genes.CONCLUSION:Gene
duplications have resulted in an extensive expansion of the superfamily
of ABC transporters in the Tetrahymena genome, making it the largest
example of its kind reported in any organism to date. Multiple independent
duplications and subsequent divergence contributed to the formation
of different families of ABC transporter genes. Many of the members
within a gene family exhibit different expression patterns. The combination
of gene duplication followed by both sequence divergence and acquisition
of new patterns of expression likely plays a role in the adaptation
of Tetrahymena to its environment.},
doi = {10.1186/1471-2148-10-330},
issn = {1471-2148},
pubmedid = {20977778},
url = {http://www.biomedcentral.com/1471-2148/10/330}
}
@ARTICLE{Xiong2007,
author = {Xiong, Qiang and Cheng, Jing},
title = {Chapter 2 Chip Capillary Electrophoresis and Total Genetic Analysis
Systems},
journal = {Perspectives Bioanalysis},
year = {2007},
volume = {Volume 2},
pages = {45--95},
abstract = {The utilization of new sequencing techniques based on capillary array
electrophoresis (CAE) has had a great impact on the progress of the
Human Genome Project (HGP), and finally led to its successful completion
at much lower costs than initially anticipated for the project (Collins
et al., 2003). Similarly, chip-based capillary electrophoresis, the
technological extension of capillary electrophoresis (CE), is a rapidly
emerging technology, which has caused revolution in analytical chemistry.
In fact, there has been an explosion of interest in the development
of chip-based CE ever since the initial concept "micro-total analysis
systems ([mu]-TAS)" or "lab-on-a-chip" was introduced by Manz and
Harrison (Manz et al., 1990; Harrison et al., 1993). With great efforts
from leading scientists, this new-born technology has matured rapidly.
It has several advantages over conventional methods, such as reduced
analysis time, high efficiency, low sample consumption, the potential
for integration and automation, disposability, portability and so
on. All these features make chip-based CE an attractive technology
for the next generation of CE instrumentation. For example, a binary
mixture could be successfully resolved in 0.8 ms using chip-based
CE separation using a field strength of 53 kV/cm, with an analysis
time of several orders of magnitudes less than conventional CE (Jacobson
et al., 1998). Other groups have applied chip-based CE for separating
FITC-labeled amino acids, and the plate heights obtained could be
down to 0.3 [mu]m, which demonstrated the high efficiency of this
separation technology (Effenhauser et al., 1993). More recently,
a microfabricated 384-lane CAE device has been developed and used
for highly parallel genetic analysis, showing great promise as a
means for ultra high-throughput bioanalysis (Emrich et al., 2002;
Paegel et al., 2003). With the maturation of these technologies,
companies have initiated industrialization of chip-based CE products.
Several commercial chip products are currently available, such as
the 5100 Automated Lab-on-a-chip Platform from Agilent Co., Ltd.,
and the Labchip 90 Electrophoresis System from Caliper Co., Ltd.
This chapter will give an overview of the chip-based CE technology,
including microchip design, fabrication and detection, surface modification
and applications.},
booktitle = {New High Throughput Technologies for DNA Sequencing and Genomics},
editor = {Mitchelson, Keith R.},
issn = {1871-0069},
publisher = {Elsevier},
url = {http://www.sciencedirect.com/science/article/B8GX0-4PT86Y3-4/2/e91ede4afb1bd60a3b2654b13fcc1847}
}
@ARTICLE{Xiong2010a,
author = {Xiong, Wei and Liu, Lixia and Wu, Chao and Yang, Chen and Wu, Qingyu},
title = {13C-Tracer and Gas Chromatography-Mass Spectrometry Analyses Reveal
Metabolic Flux Distribution in the Oleaginous Microalga Chlorella
protothecoides},
journal = {Plant Physiology},
year = {2010},
volume = {154},
pages = {1001--1011},
number = {2},
month = oct,
abstract = {The green alga Chlorella protothecoides has received considerable
attention because it accumulates neutral triacylglycerols, commonly
regarded as an ideal feedstock for biodiesel production. In order
to gain a better understanding of its metabolism, tracer experiments
with [U-13C]/[1-13C]glucose were performed with heterotrophic growth
of C. protothecoides for identifying the metabolic network topology
and estimating intracellular fluxes. Gas chromatography-mass spectrometry
analysis tracked the labeling patterns of protein-bound amino acids,
revealing a metabolic network consisting of the glycolysis, the pentose
phosphate pathway, and the tricarboxylic acid cycle with inactive
glyoxylate shunt. Evidence of phosphoenolpyruvate carboxylase, phosphoenolpyruvate
carboxykinase, and malic enzyme activity was also obtained. It was
demonstrated that the relative activity of the pentose phosphate
pathway to glycolysis under nitrogen-limited environment increased,
reflecting excess NADPH requirements for lipid biosynthesis. Although
the growth rate and cellular oil content were significantly altered
in response to nitrogen limitation, global flux distribution of C.
protothecoides remained stable, exhibiting the rigidity of central
carbon metabolism. In conclusion, quantitative knowledge on the metabolic
flux distribution of oleaginous alga obtained in this study may be
of value in designing strategies for metabolic engineering of desirable
bioproducts.},
url = {http://www.plantphysiol.org/cgi/content/abstract/154/2/1001}
}
@ARTICLE{Xiong2011,
author = {Xiong, Xiaoquan and Wang, Xiao and Li, Bing and Chowdhury, Subrata
and Lu, Yarong and Srikant, Coimbatore B. and Ning, Guang and Liu,
Jun-Li},
title = {Pancreatic islet-specific overexpression of Reg3{beta} protein induced
the expression of pro-islet genes and protected the mice against
streptozotocin-induced diabetes mellitus},
journal = {Am J Physiol Endocrinol Metab},
year = {2011},
volume = {300},
pages = {E669--680},
number = {4},
month = apr,
abstract = {Reg family proteins have been implicated in islet {beta}-cell proliferation,
survival, and regeneration. The expression of Reg3{beta} (pancreatitis-associated
protein) is highly induced in experimental diabetes and acute pancreatitis,
but its precise role has not been established. Through knockout studies,
this protein was shown to be mitogenic, antiapoptotic, and anti-inflammatory
in the liver and pancreatic acinars. To test whether it can promote
islet cell growth or survival against experimental damage, we developed
{beta}-cell-specific overexpression using rat insulin I promoter,
evaluated the changes in normal islet function, gene expression profile,
and the response to streptozotocin-induced diabetes. Significant
and specific overexpression of Reg3{beta} was achieved in the pancreatic
islets of RIP-I/Reg3{beta} mice, which exhibited normal islet histology,
{beta}-cell mass, and in vivo and in vitro insulin secretion in response
to high glucose yet were slightly hyperglycemic and low in islet
GLUT2 level. Upon streptozotocin treatment, in contrast to wild-type
littermates that became hyperglycemic in 3 days and lost 15% of their
weight, RIP-I/Reg3{beta} mice were significantly protected from hyperglycemia
and weight loss. To identify specific targets affected by Reg3{beta}
overexpression, a whole genome DNA microarray on islet RNA isolated
from the transgenic mice revealed more than 45 genes significantly
either up- or downregulated. Among them, islet-protective osteopontin/SPP1
and acute responsive nuclear protein p8/NUPR1 were significantly
induced, a result further confirmed by real-time PCR, Western blots,
and immunohistochemistry. Our results suggest that Reg3{beta} is
unlikely an islet growth factor but a putative protector that prevents
streptozotocin-induced damage by inducing the expression of specific
genes.},
comment = {10.1152/ajpendo.00600.2010},
url = {http://ajpendo.physiology.org/cgi/content/abstract/300/4/E669}
}
@ARTICLE{Xu2011,
author = {Xu, Bingfang and Abdel-Fattah, Rana and Yang, Ling and Crenshaw,
Sallie A. and Black, Michael B. and Hinton, Barry T.},
title = {Testicular Lumicrine Factors Regulate ERK, STAT, and NFKB Pathways
in the Initial Segment of the Rat Epididymis to Prevent Apoptosis},
journal = {Biol Reprod},
year = {2011},
volume = {84},
pages = {1282--1291},
number = {6},
month = jun,
abstract = {The initial segment of the epididymis is vital for male fertility;
therefore, it is important to understand the mechanisms that regulate
this important region. Deprival of testicular luminal fluid factors/lumicrine
factors from the epididymis results in a wave of apoptosis in the
initial segment. In this study, a combination of protein array and
microarray analyses was used to examine the early changes in downstream
signal transduction pathways following loss of lumicrine factors.
We discovered the following cascade of events leading to the loss
of protection and eventual apoptosis: in the first 6 h after loss
of lumicrine factors, down-regulation of the ERK pathway components
was observed at the mRNA expression and protein activity levels.
Microarray analysis revealed that mRNA levels of several key components
of the ERK pathway, Dusp6, Dusp5, and Etv5, decreased sharply, while
the analysis from the protein array revealed a decline in the activities
of MAP2K1/2 and MAPK1. Immunostaining of phospho-MAPK3/1 indicated
that down-regulation of the ERK pathway was specific to the epithelial
cells of the initial segment. Subsequently, after 12 h of loss of
lumicrine factors, levels of mRNA expression of STAT and NFKB pathway
components increased, mRNA levels of several genes encoding cell
cycle inhibitors increased, and levels of protein expression of several
proapoptotic phosphatases increased. Finally, after 18 h of loss
of protection from lumicrine factors, apoptosis was observed. In
conclusion, testicular lumicrine factors protect the cells of the
initial segment by activating the ERK pathway, repressing STAT and
NFKB pathways, and thereby preventing apoptosis.},
comment = {10.1095/biolreprod.110.090324},
url = {http://www.biolreprod.org/cgi/content/abstract/84/6/1282}
}
@ARTICLE{Xu2008,
author = {Xu, Chang and Houck, John R. and Fan, Wenhong and Wang, Pei and Chen,
Yu and Upton, Melissa and Futran, Neal D. and Schwartz, Stephen M.
and Zhao, Lue P. and Chen, Chu and Mendez, Eduardo},
title = {Simultaneous Isolation of DNA and RNA from the Same Cell Population
Obtained by Laser Capture Microdissection for Genome and Transcriptome
Profiling},
journal = {J. Mol. Diagn.},
year = {2008},
volume = {10},
pages = {129--134},
number = {2},
month = mar,
abstract = {Laser capture microdissection (LCM) is used extensively for genome
and transcriptome profiling. Traditionally, however, DNA and RNA
are purified from separate populations of LCM-harvested cells, limiting
the strength of inferences about the relationship between gene expression
and gene sequence variation. There have been no published protocols
for the simultaneous isolation of DNA and RNA from the same cells
that are obtained by LCM of patient tissue specimens. Here we report
an adaptation of the Qiagen AllPrep method that allows the purification
of DNA and RNA from the same LCM-harvested cells. We compared DNA
and RNA purified by the QIAamp DNA Micro kit and the PicoPure RNA
Isolation kit, respectively, from LCM-collected cells from adjacent
tissue sections of the same specimen. The adapted method yields 90%
of DNA and 38% of RNA compared with the individual methods. When
tested with the GeneChip 250K Nsp Array, the concordance rate of
the single nucleotide polymorphism heterozygosity calls was 98%.
When tested with the GeneChip U133 Plus 2.0 Array, the correlation
coefficient of the raw gene expression was 97%. Thus, we developed
a method to obtain both DNA and RNA material from a single population
of LCM-harvested cells and herein discuss the strengths and limitations
of this methodology.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/10/2/129}
}
@ARTICLE{Xu2009,
author = {Xu, Chenshu and Wang, Xinkun and Staudinger, Jeff L.},
title = {Regulation of Tissue-Specific Carboxylesterase Expression by Pregnane
X Receptor and Constitutive Androstane Receptor},
journal = {Drug Metab. Dispos.},
year = {2009},
volume = {37},
pages = {1539--1547},
number = {7},
month = jul,
abstract = {The liver- and intestine-enriched carboxylesterase 2 (CES2) enzyme
catalyzes the hydrolysis of several clinically important anticancer
agents administered as prodrugs. For example, irinotecan, a carbamate
prodrug used in the treatment of colorectal cancer, is biotransformed
in vivo by CES2 in intestine and liver, thereby producing a potent
topoisomerase I inhibitor. Pregnane X receptor (PXR) and constitutive
androstane receptor (CAR), two members of the nuclear receptor superfamily
of ligand-activated transcription factors, mediate gene activation
in response to xenobiotic stress. Together, these receptors comprise
a protective response in mammals that coordinately regulate hepatic
transport, metabolism, and elimination of numerous xenobiotic compounds.
In the present study, microarray analysis was used to identify PXR
target genes in duodenum in mice. Here, we show that a gene encoding
a member of the CES2 subtype of liver- and intestine-enriched CES
enzymes, called Ces6, is induced after treatment with pregnenolone
16{alpha}-carbonitrile in a PXR-dependent manner in duodenum and
liver in mice. Treatment of mice with the CAR activator 1,4-bis[2-(3,5-dichloropyridyloxy)]
benzene also induced expression of Ces6 in duodenum and liver in
a CAR-dependent manner, whereas treatment with phenobarbital produced
induction of Ces6 exclusively in liver. These data identify a key
role for PXR and CAR in regulating the drug-inducible expression
and activity of an important CES enzyme in vivo. Future studies should
focus on determining whether these signaling pathways governing drug-inducible
CES expression in intestine and liver are conserved in humans.},
url = {http://dmd.aspetjournals.org/cgi/content/abstract/37/7/1539}
}
@ARTICLE{Xu2005,
author = {Xu, Chao and Zheng, Peizheng and Shen, Shuhong and Xu, Yingqi and
Wei, Ling and Gao, Hengjun and Wang, Shengnian and Zhu, Chongri and
Tang, Yajun and Wu, Jihui and Zhang, Qinghua and Shi, Yunyu},
title = {NMR structure and regulated expression in APL cell of human SH3BGRL3},
journal = {FEBS Letters},
year = {2005},
volume = {579},
pages = {2788--2794},
number = {13},
month = may,
abstract = {SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) is
the new member of thioredoxin (TRX) super family, whose posttranslational
modified form was identified as tumor necrosis factor [alpha] (TNF-[alpha])
inhibitory protein, TIP-B1. In this paper, we determined its solution
structure by multi-dimensional nuclear magnetic resonance spectroscopy.
The overall structure of human SH3BGRL3 conformed to a TRX-like fold.
To understand its function in vivo, the upregulated expression in
acute promyelocytic leukemia cell line NB4 at both mRNA and protein
level was elucidated. Immunofluorescence and immunohistochemistry
staining with monoclonal antibody against SH3BGRL3 demonstrated that
it was a cytoplasmic protein in both NB4 cell and human tissues.
These results, as a whole, indicate that SH3BGRL3 may function as
a regulator in all-trans retinoic acid-induced pathway.},
issn = {0014-5793},
keywords = {SH3 domain binding glutamic acid-rich protein like 3, Nuclear magnetic
resonance structure, Leukemia, All-trans retinoic acid, Differentiation,
Localization},
url = {http://www.sciencedirect.com/science/article/B6T36-4G0DB3S-4/2/4d420259822e29f345564528d8a14a4d}
}
@ARTICLE{Xu2009a,
author = {Xu, Feng and Gomillion, Cheryl and Maxson, Scott and Burg, Karen
J. L.},
title = {In vitro interaction between mouse breast cancer cells and mouse
mesenchymal stem cells during adipocyte differentiation},
journal = {J Tissue Eng Regen Med},
year = {2009},
volume = {3},
pages = {338--347},
number = {5},
abstract = {Abstract 10.1002/term.158.abs Surgical treatment following breast
cancer, i.e. lumpectomy and mastectomy, may not efficiently remove
all cancerous cells. As such, when mesenchymal stem cells (MSCs)
are incorporated into the breast reconstruction process, it is likely
that those MSCs will encounter remnant cancerous cells after transplantation
into the defect site. The potential interaction between breast cancer
cells and MSCs remains unclear. We hypothesized that paracrine interactions
might occur between cells and various proteinases, growth factors
and other cytokine molecules in the local microenvironment. Conditioned
media (CM) from two mouse mammary cancer cell lines (4T1 and 4T07)
and one mouse mammary epithelial cell line (NMuMG) were studied in
the experimental model. Post-confluent mouse MSCs (D1 cells) were
differentiated with an adipogenic hormonal cocktail. Conditioned
media from the three cell types did not have an inhibitory effect
on D1 cell viability; however, triglyceride (TG) and Oil red O (ORO)
analysis results showed that 4T1-CM significantly inhibited D1 adipocyte
differentiation and reduced lipid vesicle accumulation in the differentiating
D1 cells. Preliminary analysis of the conditioned media revealed
that a higher presence of matrix metalloprotease-9 (MMP-9) and urokinase
plasminogen activator (uPA) was present in the 4T1-CM as compared
to the levels found in 4T07-CM and NMuMG-CM, which were below the
detection limit. Additionally, the conditioned medium of differentiated
D1 cells on day 12 had a negative effect on 4T1 and 4T07 cell viability
but no effect on NMuMG cell viability. The results suggest that mouse
breast cancer cells modulate mouse MSC adipogenic differentiation,
the level of modulation specific to the metastatic level. Copyright
© 2009 John Wiley & Sons, Ltd.},
issn = {1932-7005},
keywords = {adipogenic differentiation, breast cancer cells, conditioned media,
interaction, mesenchymal stem cells, mouse, tissue engineering},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/term.158}
}
@ARTICLE{Xu2011b,
author = {Xu, Fuhua and Stouffer, Richard L. and Muller, Jorg and Hennebold,
Jon D. and Wright, Jay W. and Bahar, Alistair and Leder, Gabriele
and Peters, Michaele and Thorne, Melissa and Sims, Micaela and Wintermantel,
Tim and Lindenthal, Bernhard},
title = {Dynamics of the transcriptome in the primate ovulatory follicle},
journal = {Mol. Hum. Reprod.},
year = {2011},
volume = {17},
pages = {152--165},
number = {3},
month = mar,
abstract = {Experiments were designed to evaluate changes in the transcriptome
(mRNA levels) in the ovulatory, luteinizing follicle of rhesus monkeys,
using a controlled ovulation model that permits analysis of the naturally
selected, dominant follicle at specific intervals (0, 12, 24 and
36 h) after exposure to an ovulatory (exogenous hCG) stimulus during
the menstrual cycle. Total RNA was prepared from individual follicles
(n= 4-8/timepoint), with an aliquot used for microarray analysis
(AffymetrixTM Rhesus Macaque Genome Array) and the remainder applied
to quantitative real-time PCR (q-PCR) assays. The microarray data
from individual samples distinctly clustered according to timepoints,
and ovulated follicles displayed markedly different expression patterns
from unruptured follicles at 36 h. Between timepoint comparisons
revealed profound changes in mRNA expression profiles. The dynamic
pattern of mRNA expression for steroidogenic enzymes (CYP17A, CYP19A,
HSD3B2, HSD11B1 and HSD11B2), steroidogenic acute regulatory protein
(StAR) and gonadotrophin receptors [LH/choriogonadotrophin receptor
(LHCGR), FSH receptor (FSHR)] as determined by microarray analysis
correlated precisely with those from blinded q-PCR assays. Patterns
of mRNA expression for epidermal-growth-factor-like factors (amphiregulin,
epiregulin) and processes [hyaluronan synthase 2 (HAS2), tumor necrosis
factor alpha-induced protein 6 (TNFAIP6)] implicated in cumulus-oocyte
maturation/expansion were also comparable between assays. Thus, several
mRNAs displayed the expected expression pattern for purported theca
(e.g. CYP17A), granulosa (CYP19A, FSHR), cumulus (HAS2, TNFAIP6)
cell and surface epithelium (HSD11B)-related genes in the rodent/primate
pre-ovulatory follicle. This database will be of great value in analyzing
molecular and cellular pathways associated with periovulatory events
in the primate follicle (e.g. follicle rupture, luteinization, inflammatory
response and angiogenesis), and for identifying novel gene products
controlling mammalian fertility.},
comment = {10.1093/molehr/gaq089},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/17/3/152}
}
@ARTICLE{Xu2011a,
author = {Xu, Huichun and Lu, Aigang and Sharp, Frank},
title = {Regional genome transcriptional response of adult mouse brain to
hypoxia},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {499},
number = {1},
abstract = {BACKGROUND:Since normal brain function depends upon continuous oxygen
delivery and short periods of hypoxia can precondition the brain
against subsequent ischemia, this study examined the effects of brief
hypoxia on the whole genome transcriptional response in adult mouse
brain.RESULT:Pronounced changes of gene expression occurred after
3 hours of hypoxia (8% O2) and after 1 hour of re-oxygenation in
all brain regions. The hypoxia-responsive genes were predominantly
up-regulated in hindbrain and predominantly down-regulated in forebrain
- possibly to support hindbrain survival functions at the expense
of forebrain cognitive functions. The up-regulated genes had a significant
role in cell survival and involved both shared and unshared signaling
pathways among different brain regions. Up-regulation of transcriptional
signaling including hypoxia inducible factor, insulin growth factor
(IGF), the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid
signaling was common to many brain regions. However, many of the
hypoxia-regulated target genes were specific for one or a few brain
regions. Cerebellum, for example, had 1241 transcripts regulated
by hypoxia only in cerebellum but not in hippocampus; and, 642 (54%)
had at least one hepatic nuclear receptor 4A (HNF4A) binding site
and 381 had at least two HNF4A binding sites in their promoters.
The data point to HNF4A as a major hypoxia-responsive transcription
factor in cerebellum in addition to its known role in regulating
erythropoietin transcription. The genes unique to hindbrain may play
critical roles in survival during hypoxia.CONCLUSION:Differences
of forebrain and hindbrain hypoxia-responsive genes may relate to
suppression of forebrain cognitive functions and activation of hindbrain
survival functions, which may coordinately mediate the neuroprotection
afforded by hypoxia preconditioning.},
doi = {10.1186/1471-2164-12-499},
issn = {1471-2164},
pubmedid = {21988864},
url = {http://www.biomedcentral.com/1471-2164/12/499}
}
@ARTICLE{Xu2009b,
author = {Xu, H. and Lui, W.T. and Chu, C.Y. and Ng, P.S. and Wang, C.C. and
Rogers, M.S.},
title = {Anti-angiogenic effects of green tea catechin on an experimental
endometriosis mouse model},
journal = {Hum. Reprod.},
year = {2009},
volume = {24},
pages = {608--618},
number = {3},
month = mar,
abstract = {BACKGROUNDThe development of new blood vessels plays an essential
role in growth and survival of endometriosis. Epigallocatechin gallate
(EGCG) from green tea has powerful anti-angiogenic properties and
our aim was to evaluate these properties in experimental endometriosis.
METHODS AND RESULTSEutopic endometrium from endometriosis patients
was transplanted s.c. to severely compromised immunodeficient mice,
randomly treated i.p. with EGCG (anti-angiogenic and -oxidant), Vitamin
E (a non-angiogenic antioxidant) or saline for 2 weeks. The endometrial
implant, including adjacent host outer skin and subcutaneous layers
plus inner abdominal muscle and peritoneum, was collected. New microvessels
were determined by species-specific immunohistochemistry. Angiogenic
factors in lesions and abdominal muscle were detected by quantitative
real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase-mediated
dUTP nick-end labelling and quantitative real-time PCR. In saline
control, endometrial implants developed new blood vessels with proliferating
glandular epithelium and were tightly adhered to host subcutaneous
and abdominal muscle layers. After EGCG, endometriotic lesions were
smaller than control (P < 0.05), and glandular epithelium was smaller
and eccentrically distributed. Angiogenesis in lesions from the implant
and adjacent tissues was under-developed, and microvessel size and
density were lower (both P < 0.01) than control. mRNA for angiogenic
vascular endothelial growth factor A, but not hypoxia inducible factor
1, alpha subunit, was significantly down-regulated in lesions after
EGCG (P < 0.05). In addition, apoptosis in the lesions was more obvious,
and nuclear factor kappa B and mitogen activated protein kinase 1
mRNA levels were up-regulated (P < 0.05) after EGCG treatment. No
differences were observed with Vitamin E treatment. CONCLUSIONSEGCG
significantly inhibits the development of experimental endometriosis
through anti-angiogenic effects.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/24/3/608}
}
@ARTICLE{Xu2007,
author = {Xu, Jihong and Drew, Paul D.},
title = {Peroxisome Proliferator-Activated Receptor-{gamma} Agonists Suppress
the Production of IL-12 Family Cytokines by Activated Glia},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {1904--1913},
number = {3},
month = feb,
abstract = {The IL-12 family of cytokines, which include IL-12, IL-23, and IL-27,
play critical roles in the differentiation of Th1 cells and are believed
to contribute to the development of multiple sclerosis (MS) and experimental
autoimmune encephalomyelitis (EAE), an animal model of MS. Relatively
little is known concerning the expression of IL-12 family cytokines
by cells of the CNS, the affected tissue in MS. Previously, we and
others demonstrated that peroxisome proliferator-activated receptor
(PPAR)-{gamma} agonists suppress the development of EAE, alter T
cell proliferation and phenotype, and suppress the activation of
APCs. The present studies demonstrated that PPAR-{gamma} agonists,
including the naturally occurring 15-deoxy-{Delta}12,14-PGJ2 and
the synthetic thiazoladinedione rosiglitazone, inhibited the induction
of IL-12p40, IL-12p70 (p35/p40), IL-23 (p19/p40), and IL-27p28 proteins
by LPS-stimulated primary microglia. In primary astrocytes, LPS induced
the production of IL-12p40, IL-23, and IL-27p28 proteins. However,
IL-12p70 production was not detected in these cells. The 15-deoxy-{Delta}12,14-PGJ2
potently suppressed IL-12p40, IL-23, and IL-27p28 production by primary
astrocytes, whereas rosiglitazone suppressed IL-23 and IL-27p28,
but not IL-12p40 in these cells. These novel observations suggest
that PPAR-{gamma} agonists modulate the development of EAE, at least
in part, by inhibiting the production of IL-12 family cytokines by
CNS glia. In addition, we demonstrate that PPAR-{gamma} agonists
inhibit TLR2, MyD88, and CD14 expression in glia, suggesting a possible
mechanism by which these agonists modulate IL-12 family cytokine
expression. Collectively, these studies suggest that PPAR-{gamma}
agonists may be beneficial in the treatment of MS.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/3/1904}
}
@ARTICLE{Xu2003,
author = {Xu, Jimin and Moatamed, Farhad and Caldwell, Jeremy S. and Walker,
John R. and Kraiem, Zaki and Taki, Katsumi and Brent, Gregory A.
and Hershman, Jerome M.},
title = {Enhanced Expression of Nicotinamide N-Methyltransferase in Human
Papillary Thyroid Carcinoma Cells},
journal = {J. Clin. Endocrinol. Metab.},
year = {2003},
volume = {88},
pages = {4990--4996},
number = {10},
month = oct,
abstract = {To gain an understanding of the molecular pathogenesis of thyroid
cancer, we used DNA microarray to study the expression profiles of
10 different human thyroid carcinoma cell lines. These included papillary
lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic
lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary
line HRO 85-1. Among the genes with increased expression in the cancer
cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT)
was identified for being highly expressed only in the papillary cell
lines. NNMT catalyzes N-methylation of nicotinamide and other structurally
related compounds and is highly expressed in the human liver. The
results were further confirmed by semiquantitative RT-PCR and Northern
blot analysis. NNMT catalytic activities were determined in all of
the cells described above and in additional cell lines. Significantly
higher NNMT enzyme activities were detected in eight of 10 of the
papillary lines and three of six of the follicular cell lines tested.
Normal thyroid tissue, thyroid primary cultures, anaplastic cancer
cells, and medullary cancer cells showed no or low enzyme activity.
Immunohistochemical staining for NNMT of human thyroid specimens
showed strong and abundant cytoplasmic reactions in the sections
of papillary carcinomas, and weak or scanty reaction in the normal
thyroid tissues. These results indicate that NNMT is a potential
biomarker for papillary thyroid carcinoma.},
url = {http://jcem.endojournals.org/cgi/content/abstract/88/10/4990}
}
@ARTICLE{Xu2010,
author = {Xu, Jie and Yang, Caiyun and Yuan, Zheng and Zhang, Dasheng and Gondwe,
Martha Y. and Ding, Zhiwen and Liang, Wanqi and Zhang, Dabing and
Wilson, Zoe A.},
title = {The aborted microspores regulatory network is required for postmeiotic
male reproductive development in arabidopsis thaliana},
journal = {PLANT CELL},
year = {2010},
volume = {22},
pages = {91--107},
number = {1},
month = jan,
abstract = {The Arabidopsis thaliana ABORTED MICROSPORES (AMS) gene encodes a
basic helix-loop-helix (bHLH) transcription factor that is required
for tapetal cell development and postmeiotic microspore formation.
However, the regulatory role of AMS in anther and pollen development
has not been fully defined. Here, we show by microarray analysis
that the expression of 549 anther-expressed genes was altered in
ams buds and that these genes are associated with tapetal function
and pollen wall formation. We demonstrate that AMS has the ability
to bind in vitro to DNA containing a 6-bp consensus motif, CANNTG.
Moreover, 13 genes involved in transportation of lipids, oligopeptides,
and ions, fatty acid synthesis and metabolism, flavonol accumulation,
substrate oxidation, methyl-modification, and pectin dynamics were
identified as direct targets of AMS by chromatin immunoprecipitation.
The functional importance of the AMS regulatory pathway was further
demonstrated by analysis of an insertional mutant of one of these
downstream AMS targets, an ABC transporter, White-Brown Complex homolog,
which fails to undergo pollen development and is male sterile. Yeast
two-hybrid screens and pull-down assays revealed that AMS has the
ability to interact with two bHLH proteins (AtbHLH089 and AtbHLH091)
and the ATA20 protein. These results provide insight into the regulatory
role of the AMS network during anther development.},
url = {http://www.plantcell.org/cgi/content/abstract/22/1/91}
}
@ARTICLE{Xu2009c,
author = {Xu, Li and Ding, Yongzeng and Catalona, William J. and Yang, Ximing
J. and Anderson, Wayne F. and Jovanovic, Borko and Wellman, Kenji
and Killmer, Jaqueline and Huang, Xiaoke and Scheidt, Karl A. and
Montgomery, R. Bruce and Bergan, Raymond C.},
title = {MEK4 Function, Genistein Treatment, and Invasion of Human Prostate
Cancer Cells},
journal = {J Natl Cancer Inst},
year = {2009},
volume = {101},
pages = {1141--1155},
number = {16},
month = aug,
abstract = {BackgroundDietary intake of genistein by patients with prostate cancer
has been associated with decreased metastasis and mortality. Genistein
blocks activation of p38 mitogen-activated protein kinase and thus
inhibits matrix metalloproteinase-2 (MMP-2) expression and cell invasion
in cultured cells and inhibits metastasis of human prostate cancer
cells in mice. We investigated the target for genistein in prostate
cancer cells. MethodsProstate cell lines PC3-M, PC3, 1532NPTX, 1542NPTX,
1532CPTX, and 1542CPTX were used. All cell lines were transiently
transfected with a constitutively active mitogen-activated protein
kinase kinase 4 (MEK4) expression vector (to increase MEK4 expression),
small interfering RNA against MEK4 (to decrease MEK4 expression),
or corresponding control constructs. Cell invasion was assessed by
a Boyden chamber assay. Gene expression was assessed by a quantitative
reverse transcription-polymerase chain reaction. Protein expression
was assessed by Western blot analysis. Modeller and AutoDock programs
were used for modeling of the structure of MEK4 protein and ligand
docking, respectively. MMP-2 transcript levels were assessed in normal
prostate epithelial cells from 24 patients with prostate cancer from
a phase II randomized trial comparing genistein treatment with no
treatment. Statistical significance required a P value of .050 or
less. All statistical tests were two-sided. ResultsOverexpression
of MEK4 increased MMP-2 expression and cell invasion in all six cell
lines. Decreased MEK4 expression had the opposite effects. Modeling
showed that genistein bound to the active site of MEK4. Genistein
inhibited MEK4 kinase activity with a half maximal inhibitory concentration
of 0.40 {micro}M (95% confidence interval [CI] = 0.36 to 0.45 {micro}M).
The MMP-2 transcript level in normal prostate epithelial cells was
statistically significantly higher in the untreated group (100%)
than in the genistein-treated group (24%; difference = 76%, 95% CI
= 38% to 115%; P = .045). ConclusionsWe identified MEK4 as a proinvasion
protein in six human prostate cancer cell lines and the target for
genistein. We showed, to our knowledge for the first time, that genistein
treatment, compared with no treatment, was associated with decreased
levels of MMP-2 transcripts in normal prostate cells from prostate
cancer-containing tissue.},
url = {http://jnci.oxfordjournals.org/cgi/content/abstract/101/16/1141}
}
@ARTICLE{Xu2009d,
author = {Xu, Lei and Duda, Dan G. and di Tomaso, Emmanuelle and Ancukiewicz,
Marek and Chung, Daniel C. and Lauwers, Gregory Y. and Samuel, Rekha
and Shellito, Paul and Czito, Brian G. and Lin, Pei-Chun and Poleski,
Martin and Bentley, Rex and Clark, Jeffrey W. and Willett, Christopher
G. and Jain, Rakesh K.},
title = {Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates
SDF1{alpha}, CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients
with Rectal Cancer},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {7905--7910},
number = {20},
month = oct,
abstract = {Clinical studies converge on the observation that circulating cytokines
are elevated in most cancer patients by anti-vascular endothelial
growth factor (VEGF) therapy. However, the source of these molecules
and their relevance in tumor escape remain unknown. We examined the
gene expression profiles of cancer cells and tumor-associated macrophages
in tumor biopsies before and 12 days after monotherapy with the anti-VEGF
antibody bevacizumab in patients with rectal carcinoma. Bevacizumab
up-regulated stromal cell-derived factor 1{alpha} (SDF1{alpha}),
its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and
Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and
induced neuropilin 1 (NRP1) expression in tumor-associated macrophages.
Higher SDF1{alpha} plasma levels during bevacizumab treatment significantly
associated with distant metastasis at three years. These data show
that VEGF blockade up-regulates inflammatory pathways and NRP1, which
should be evaluated as potential targets for improving anti-VEGF
therapy. [Cancer Res 2009;69(20):7905-10]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/20/7905}
}
@ARTICLE{Xu2005a,
author = {Xu, L and Hui, A Y and Albanis, E and Arthur, M J and O'Byrne, S
M and Blaner, W S and Mukherjee, P and Friedman, S L and Eng, F J},
title = {Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis
of hepatic fibrosis},
journal = {Gut},
year = {2005},
volume = {54},
pages = {142--151},
number = {1},
month = jan,
abstract = {Background: Hepatic stellate cells (HSCs) are a major fibrogenic cell
type that contributes to collagen accumulation during chronic liver
disease. With increasing interest in developing antifibrotic therapies,
there is a need for cell lines that preserve the in vivo phenotype
of human HSCs to elucidate pathways of human hepatic fibrosis. We
established and characterised two human HSC cell lines termed LX-1
and LX-2, and compared their features with those of primary human
stellate cells. Methods and results: LX-1 and LX-2 were generated
by either SV40 T antigen immortalisation (LX-1) or spontaneous immortalisation
in low serum conditions (LX-2). Both lines express {alpha} smooth
muscle actin, vimentin, and glial fibrillary acid protein, as visualised
by immunocytochemistry. Similar to primary HSCs, both lines express
key receptors regulating hepatic fibrosis, including platelet derived
growth factor receptor {beta} ({beta}PDGF-R), obese receptor long
form (Ob-RL), and discoidin domain receptor 2 (DDR2), and also proteins
involved in matrix remodelling; matrix metalloproteinase (MMP)-2,
tissue inhibitor of matrix metalloproteinase (TIMP)-2, and MT1-MMP,
as determined by western analyses. LX-2 have reduced expression of
TIMP-1. LX-2, but not LX-1, proliferate in response to PDGF. Both
lines express mRNAs for {alpha}1(I) procollagen and HSP47. Transforming
growth factor {beta}1 stimulation increased their {alpha}1(I) procollagen
mRNA expression, as determined by quantitative reverse transcription-polymerase
chain reaction. LX-2, but not LX-1, cells are highly transfectable.
Both lines had a retinoid phenotype typical of stellate cells. Microarray
analyses showed strong similarity in gene expression between primary
HSCs and either LX-1 (98.4%) or LX-2 (98.7%), with expression of
multiple neuronal genes. Conclusions: LX-1 and LX-2 human HSC lines
provide valuable new tools in the study of liver disease. Both lines
retain key features of HSCs. Two unique advantages of LX-2 are their
viability in serum free media and high transfectability.},
url = {http://gut.bmj.com/cgi/content/abstract/54/1/142}
}
@ARTICLE{Xu2007a,
author = {Xu, Rui and Chandrasekharan, Kumaran and Yoon, Jung Hae and Camboni,
Marybeth and Martin, Paul T.},
title = {Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits
Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular
Dystrophy 1A},
journal = {Am. J. Pathol.},
year = {2007},
volume = {171},
pages = {181--199},
number = {1},
month = jul,
abstract = {A number of recent studies have demonstrated therapeutic effects of
transgenes on the development of muscle pathology in the mdx mouse
model for Duchenne muscular dystrophy, but none have been shown also
to be effective in mouse models for laminin {alpha}2-deficient congenital
muscular dystrophy (MDC1A). Here, we show that overexpression of
the cytotoxic T cell (CT) GalNAc transferase (Galgt2) is effective
in inhibiting the development of muscle pathology in the dyW mouse
model of MDC1A, much as we had previously shown in mdx animals. Embryonic
overexpression of Galgt2 in skeletal muscles using transgenic mice
or postnatal overexpression using adeno-associated virus both reduced
the extent of muscle pathology in dyW/dyW skeletal muscle. As with
mdx mice, embryonic overexpression of the Galgt2 transgene in dyW/dyW
myofibers inhibited muscle growth, whereas postnatal overexpression
did not. Both embryonic and postnatal overexpression of Galgt2 in
dyW/dyW muscle increased the expression of agrin, a protein that,
in recombinant form, has been shown to ameliorate disease, whereas
laminin {alpha}1, another disease modifier, was not expressed. Galgt2
over-expression also stimulated the glycosylation of a gly-colipid
with the CT carbohydrate, and glycolipids accounted for most of the
CT-reactive material in postnatal overexpression experiments. These
experiments demonstrate that Galgt2 overexpression is effective in
altering disease progression in skeletal muscles of dyW mice and
should be considered as a therapeutic target in MDC1A.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/171/1/181}
}
@ARTICLE{Xu2009e,
author = {Xu, Rui and DeVries, Sarah and Camboni, Marybeth and Martin, Paul
T.},
title = {Overexpression of Galgt2 Reduces Dystrophic Pathology in the Skeletal
Muscles of Alpha Sarcoglycan-Deficient Mice},
journal = {Am. J. Pathol.},
year = {2009},
volume = {175},
pages = {235--247},
number = {1},
month = jul,
abstract = {Recent studies have shown that a number of genes that are not mutated
in various forms of muscular dystrophy may serve as surrogates to
protect skeletal myofibers from injury. One such gene is Galgt2,
which is also called cytotoxic T cell GalNAc transferase in mice.
In this study, we show that Galgt2 overexpression reduces the development
of dystrophic pathology in the skeletal muscles of mice lacking {alpha}
sarcoglycan (Sgca), a mouse model for limb girdle muscular dystrophy
2D. Galgt2 transgenic Sgca-/- mice showed reduced levels of myofiber
damage, as evidenced by i) normal levels of serum creatine kinase
activity, ii) a lack of Evans blue dye uptake into myofibers, iii)
normal levels of mouse locomotor activity, and iv) near normal percentages
of myofibers with centrally located nuclei. In addition, the overexpression
of Galgt2 in the early postnatal period using an adeno-associated
virus gene therapy vector protected Sgca-/- myofibers from damage,
as observed using histopathology measurements. Galgt2 transgenic
Sgca-/- mice also had increased levels of glycosylation of {alpha}
dystroglycan with the CT carbohydrate, but showed no up-regulation
of {beta}, {gamma}, {delta}, or {epsilon} sarcoglycan. These data,
coupled with results from our previous studies, show that Galgt2
has therapeutic effects in three distinct forms of muscular dystrophy
and may, therefore, have a broad spectrum of therapeutic potential
for the treatment of various myopathies.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/175/1/235}
}
@ARTICLE{Xu2004,
author = {Xu, Tong and Shu, Chen-Tsen and Purdom, Elizabeth and Dang, Demi
and Ilsley, Diane and Guo, Yaqian and Weber, Jeffrey and Holmes,
Susan P. and Lee, Peter P.},
title = {Microarray Analysis Reveals Differences in Gene Expression of Circulating
CD8+ T Cells in Melanoma Patients and Healthy Donors},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {3661--3667},
number = {10},
month = may,
abstract = {Circulating T cells from many cancer patients are known to be dysfunctional
and undergo spontaneous apoptosis. We used microarray technology
to determine whether gene expression differences exist in T cells
from melanoma patients versus healthy subjects, which may underlie
these abnormalities. To maximize the resolution of our data, we sort
purified CD8+ subsets and amplified the extracted RNA for microarray
analysis. These analyses show subtle but statistically significant
expression differences for 10 genes in T cells from melanoma patients
versus healthy controls, which were additionally confirmed by quantitative
real-time PCR analysis. Whereas none of these genes are members of
the classical apoptosis pathways, several may be linked to apoptosis.
To additionally investigate the significance of these 10 genes, we
combined them into a classifier and found that they provide a much
better discrimination between melanoma and healthy T cells as compared
with a classifier built uniquely with classical apoptosis-related
genes. These results suggest the possible engagement of an alternative
apoptosis pathway in circulating T cells from cancer patients.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/10/3661}
}
@ARTICLE{Xu2010a,
author = {Xu, Wei and Faisal, Mohamed},
title = {Factorial microarray analysis of zebra mussel (Dreissena polymorpha:
Dreissenidae, Bivalvia) adhesion},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {341},
number = {1},
abstract = {BACKGROUND:The zebra mussel (Dreissena polymorpha) has been well known
for its expertise in attaching to substances under the water. Studies
in past decades on this underwater adhesion focused on the adhesive
protein isolated from the byssogenesis apparatus of the zebra mussel.
However, the mechanism of the initiation, maintenance, and determination
of the attachment process remains largely unknown.RESULTS:In this
study, we used a zebra mussel cDNA microarray previously developed
in our lab and a factorial analysis to identify the genes that were
involved in response to the changes of four factors: temperature
(Factor A), current velocity (Factor B), dissolved oxygen (Factor
C), and byssogenesis status (Factor D). Twenty probes in the microarray
were found to be modified by one of the factors. The transcription
products of four selected genes, DPFP-BG20_A01, EGP-BG97/192_B06,
EGP-BG13_G05, and NH-BG17_C09 were unique to the zebra mussel foot
based on the results of quantitative reverse transcription PCR (qRT-PCR).
The expression profiles of these four genes under the attachment
and non-attachment were also confirmed by qRT-PCR and the result
is accordant to that from microarray assay. The in situ hybridization
with the RNA probes of two identified genes DPFP-BG20_A01 and EGP-BG97/192_B06
indicated that both of them were expressed by a type of exocrine
gland cell located in the middle part of the zebra mussel foot.CONCLUSIONS:The
results of this study suggested that the changes of D. polymorpha
byssogenesis status and the environmental factors can dramatically
affect the expression profiles of the genes unique to the foot. It
turns out that the factorial design and analysis of the microarray
experiment is a reliable method to identify the influence of multiple
factors on the expression profiles of the probesets in the microarray;
therein it provides a powerful tool to reveal the mechanism of zebra
mussel underwater attachment.},
doi = {10.1186/1471-2164-11-341},
issn = {1471-2164},
pubmedid = {20509938},
url = {http://www.biomedcentral.com/1471-2164/11/341}
}
@ARTICLE{Xu2007b,
author = {Xu, Xiaoqin and Bieda, Mark and Jin, Victor X. and Rabinovich, Alina
and Oberley, Mathew J. and Green, Roland and Farnham, Peggy J.},
title = {A comprehensive ChIP chip analysis of E2F1, E2F4, and E2F6 in normal
and tumor cells reveals interchangeable roles of E2F family members},
journal = {Genome Res.},
year = {2007},
volume = {17},
pages = {1550--1561},
number = {11},
month = nov,
abstract = {Using ChIP-chip assays (employing ENCODE arrays and core promoter
arrays), we examined the binding patterns of three members of the
E2F family in five cell types. We determined that most E2F1, E2F4,
and E2F6 binding sites are located within 2 kb of a transcription
start site, in both normal and tumor cells. In fact, the majority
of promoters that are active (as defined by TAF1 or POLR2A binding)
in GM06990 B lymphocytes and Ntera2 carcinoma cells were also bound
by an E2F. This very close relationship between E2F binding sites
and binding sites for general transcription factors in both normal
and tumor cells suggests that a chromatin-bound E2F may be a signpost
for active transcription initiation complexes. In general, we found
that several E2Fs bind to a given promoter and that there is only
modest cell type specificity of the E2F family. Thus, it is difficult
to assess the role of any particular E2F in transcriptional regulation,
due to extreme redundancy of target promoters. However, Ntera2 carcinoma
cells were exceptional in that a large set of promoters were bound
by E2F6, but not by E2F1 or E2F4. It has been proposed that E2F6
contributes to gene silencing by recruiting enzymes involved in methylating
histone H3. To test this hypothesis, we created Ntera2 cell lines
harboring shRNAs to E2F6. We found that reduction of E2F6 only induced
minimal alteration of the transcriptome of Ntera2 transcriptome.
Our results support the concept of functional redundancy in the E2F
family and suggest that E2F6 is not critical for histone methylation.},
url = {http://genome.cshlp.org/cgi/content/abstract/17/11/1550}
}
@ARTICLE{Xu2008a,
author = {Xu, Xiaobo and D'Hoker, Joke and Stangé, Geert and Bonné, Stefan
and De Leu, Nico and Xiao, Xiangwei and Van De Casteele, Mark and
Mellitzer, Georg and Ling, Zhidong and Pipeleers, Danny and Bouwens,
Luc and Scharfmann, Raphael and Gradwohl, Gerard and Heimberg, Harry},
title = {[beta] Cells Can Be Generated from Endogenous Progenitors in Injured
Adult Mouse Pancreas},
journal = {Cell},
year = {2008},
volume = {132},
pages = {197--207},
number = {2},
month = jan,
abstract = {Summary Novel strategies in diabetes therapy would obviously benefit
from the use of beta ([beta]) cell stem/progenitor cells. However,
whether or not adult [beta] cell progenitors exist is one of the
most controversial issues in today's diabetes research. Guided by
the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific
transcription factor in embryonic development, we show that [beta]
cell progenitors can be activated in injured adult mouse pancreas
and are located in the ductal lining. Differentiation of the adult
progenitors is Ngn3 dependent and gives rise to all islet cell types,
including glucose responsive [beta] cells that subsequently proliferate,
both in situ and when cultured in embryonic pancreas explants. Multipotent
progenitor cells thus exist in the pancreas of adult mice and can
be activated cell autonomously to increase the functional [beta]
cell mass by differentiation and proliferation rather than by self-duplication
of pre-existing [beta] cells only.},
issn = {0092-8674},
keywords = {STEMCELL, DEVBIO, HUMDISEASE},
url = {http://www.sciencedirect.com/science/article/B6WSN-4RNK38M-9/2/d8e62bd5cd47d120f399b8e0009279e8}
}
@ARTICLE{Xu2007c,
author = {Xu, Xiangru and Zhan, Ming and Duan, Wenzhen and Prabhu, Vinayakumar
and Brenneman, Randall and Wood, William and Firman, Jeff and Li,
Huai and Zhang, Peisu and Ibe, Carol and Zonderman, Alan and Longo,
Dan and Poosala, Suresh and Becker, Kevin and Mattson, Mark},
title = {Gene expression atlas of the mouse central nervous system: impact
and interactions of age, energy intake and gender},
journal = {Genome Biology},
year = {2007},
volume = {8},
pages = {R234},
number = {11},
abstract = {BACKGROUND:The structural and functional complexity of the mammalian
central nervous system (CNS) is organized and modified by complicated
molecular signaling processes that are poorly understood.RESULTS:We
measured transcripts of 16,896 genes in 5 CNS regions from cohorts
of young, middle-aged and old male and female mice that had been
maintained on either a control diet or a low energy diet known to
retard aging. Each CNS region (cerebral cortex, hippocampus, striatum,
cerebellum and spinal cord) possessed its own unique transcriptome
fingerprint that was independent of age, gender and energy intake.
Less than 10% of genes were significantly affected by age, diet or
gender, with most of these changes occurring between middle and old
age. The transcriptome of the spinal cord was the most responsive
to age, diet and gender, while the striatal transcriptome was the
least responsive. Gender and energy restriction had particularly
robust influences on the hippocampal transcriptome of middle-aged
mice. Prominent functional groups of age- and energy-sensitive genes
were those encoding proteins involved in DNA damage responses (Werner
and telomere-associated proteins), mitochondrial and proteasome functions,
cell fate determination (Wnt and Notch signaling) and synaptic vesicle
trafficking.CONCLUSION:Mouse CNS transcriptomes responded to age,
energy intake and gender in a regionally distinctive manner. The
systematic transcriptome dataset also provides a window into mechanisms
of age-, diet- and sex-related CNS plasticity and vulnerability.},
doi = {10.1186/gb-2007-8-11-r234},
issn = {1465-6906},
owner = {Meike Kuschel},
pubmedid = {17988385},
timestamp = {2010.04.07},
url = {http://genomebiology.com/2007/8/11/R234}
}
@ARTICLE{Xu2006,
author = {Xu, Yun and Zhang, Wenri and Klaus, Judith and Young, Jennifer and
Koerner, Ines and Sheldahl, Laird C. and Hurn, Patricia D. and Martinez-Murillo,
Francisco and Alkayed, Nabil J.},
title = {Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated
neuroprotection},
journal = {PNAS},
year = {2006},
volume = {103},
pages = {14489--14494},
number = {39},
month = sep,
abstract = {Estrogen reduces brain injury after experimental cerebral ischemia
in part through a genomic mechanism of action. Using DNA microarrays,
we analyzed the genomic response of the brain to estradiol, and we
identified a transcript, cocaine- and amphetamine-regulated transcript
(CART), that is highly induced in the cerebral cortex by estradiol
under ischemic conditions. Using in vitro and in vivo models of neural
injury, we confirmed and characterized CART mRNA and protein up-regulation
by estradiol in surviving neurons, and we demonstrated that i.v.
administration of a rat CART peptide is protective against ischemic
brain injury in vivo. We further demonstrated binding of cAMP response
element (CRE)-binding protein to a CART promoter CRE site in ischemic
brain and rapid activation by CART of ERK in primary cultured cortical
neurons. The findings suggest that CART is an important player in
estrogen-mediated neuroprotection and a potential therapeutic agent
for stroke and other neurodegenerative diseases.},
url = {http://www.pnas.org/cgi/content/abstract/103/39/14489}
}
@ARTICLE{Xue2010b,
author = {Xue, Jin and Mraiche, Fatima and Zhou, Dan and Karmazyn, Morris and
Oka, Tatsujiro and Fliegel, Larry and Haddad, Gabriel G.},
title = {Elevated myocardial Na+/H+ exchanger isoform 1 activity elicits gene
expression that leads to cardiac hypertrophy},
journal = {Physiol Genomics},
year = {2010},
volume = {42},
pages = {374--383},
number = {3},
month = aug,
abstract = {In myocardial disease, elevated expression and activity of Na+/H+
exchanger isoform 1 (NHE1) are detrimental. To better understand
the involvement of NHE1, transgenic mice with elevated heart-specific
NHE1 expression were studied. N-line mice expressed wild-type NHE1,
and K-line mice expressed activated NHE1. Cardiac morphology, interstitial
fibrosis, and cardiac function were examined by histological staining
and echocardiography. Differences in gene expression between the
N-line or K-line and nontransgenic littermates were probed with genechip
analysis. We found that NHE1 K-line (but not N-line) hearts developed
hypertrophy, including elevated heart weight-to-body weight ratio
and increased cross-sectional area of the cardiomyocytes, interstitial
fibrosis, as well as depressed cardiac function. N-line hearts had
modest changes in gene expression (50 upregulations and 99 downregulations,
P < 0.05), whereas K-line hearts had a very strong transcriptional
response (640 upregulations and 677 downregulations, P < 0.05). In
addition, the magnitude of expression alterations was much higher
in K-line than N-line mice. The most significant changes in gene
expression were involved in cardiac hypertrophy, cardiac necrosis/cell
death, and cardiac infarction. Secreted phosphoprotein 1 and its
signaling pathways were upregulated while peroxisome proliferator-activated
receptor {gamma} signaling was downregulated in K-line mice. Our
study shows that expression of activated NHE1 elicits specific pathways
of gene activation in the myocardium that lead to cardiac hypertrophy,
cell death, and infarction.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/42/3/374}
}
@ARTICLE{Xue2010,
author = {Xue, Xiaoli and Tomasch, Jurgen and Sztajer, Helena and Wagner-Dobler,
Irene},
title = {The Delta Subunit of RNA Polymerase, RpoE, Is a Global Modulator
of Streptococcus mutans Environmental Adaptation},
journal = {J. Bacteriol.},
year = {2010},
volume = {192},
pages = {5081--5092},
number = {19},
month = oct,
abstract = {The delta subunit of RNA polymerase, RpoE, is widespread in low-G+C
Gram-positive bacteria and is thought to play a role in enhancing
transcriptional specificity by blocking RNA polymerase binding at
weak promoter sites and stimulating RNA synthesis by accelerating
core enzyme recycling. Despite the well-studied biochemical properties
of RpoE, a role for this protein in vivo has not been defined in
depth. In this study, we show that inactivation of rpoE in the human
dental caries pathogen Streptococcus mutans causes impaired growth
and loss of important virulence traits, including biofilm formation,
resistance to antibiotics, and tolerance to environmental stresses.
Complementation of the mutant with rpoE expressed in trans restored
its phenotype to wild type. The luciferase fusion reporter showed
that rpoE was highly transcribed throughout growth and that acid
and hydrogen peroxide stresses repressed rpoE expression. Transcriptome
profiling of wild-type and {Delta}rpoE cells in the exponential and
early stationary phase of growth, under acid and hydrogen peroxide
stress and under both stresses combined, revealed that genes involved
in histidine synthesis, malolactic fermentation, biofilm formation,
and antibiotic resistance were downregulated in the {Delta}rpoE mutant
under all conditions. Moreover, the loss of RpoE resulted in dramatic
changes in transport and metabolism of carbohydrates and amino acids.
Interestingly, differential expression, mostly upregulation, of 330
noncoding regions was found. In conclusion, this study demonstrates
that RpoE is an important global modulator of gene expression in
S. mutans which is required for optimal growth and environmental
adaptation.},
url = {http://jb.asm.org/cgi/content/abstract/192/19/5081}
}
@ARTICLE{Xue2010a,
author = {Xue, Y. and Liao, S. F. and Son, K. W. and Greenwood, S. L. and McBride,
B. W. and Boling, J. A. and Matthews, J. C.},
title = {Metabolic acidosis in sheep alters expression of renal and skeletal
muscle amino acid enzymes and transporters},
journal = {J Anim Sci},
year = {2010},
volume = {88},
pages = {707--717},
number = {2},
month = feb,
abstract = {To determine the effect of metabolic acidosis on expression of L-Gln,
L-Glu, and L-Asp metabolizing enzymes and transporters, the relative
content of mRNA, protein, or mRNA and protein, of 6 enzymes and 5
transporters was determined by real-time reverse transcription-PCR
and immunoblot analyses in homogenates of kidney, skeletal muscle,
and liver of growing lambs fed a common diet supplemented with canola
meal (control; n = 5) or HCl-treated canola meal (acidosis; n = 5).
Acidotic sheep had a 790% greater (P = 0.050) expression of renal
Na+-coupled neutral AA transporter 3 mRNA and a decreased expression
of renal glutamine synthetase mRNA (47% reduction, P = 0.037) and
protein (57% reduction, P = 0.015) than control sheep. No change
in renal cytosolic phosphoenolpyruvate carboxykinase (protein and
mRNA), glutaminase (mRNA), or L-Glu dehydrogenase (protein) was found.
In skeletal muscle, acidotic sheep had 101% more (P = 0.026) aspartate
transaminase protein than did control sheep, whereas no change in
the content of 3 Na+-coupled neutral AA transporters (mRNA) or 2
high-affinity L-Glu transporter proteins was found. In liver, no
change in the content of any assessed enzyme or transporter was found.
Collectively, these findings suggest that tissue-level responses
of sheep to metabolic acidosis are different than for nonruminants.
More specifically, these results indicate the potential capacity
for metabolism of L-Asp and L-Glu by skeletal muscle, and L-Gln absorption
by kidneys, but no change in hepatic expression of L-Gln metabolism,
elaborates previous metabolic studies by revealing molecular-level
responses to metabolic acidosis in sheep. The reader is cautioned
that the metabolic acidosis model employed in this study differs
from the increased plasma lactate-induced metabolic acidosis commonly
observed in ruminants fed a highly fermentable grain diet.},
url = {http://jas.fass.org/cgi/content/abstract/88/2/707}
}
@ARTICLE{Xue2007,
author = {Xue, Zhixiong and McCluskey, Michael and Cantera, Keith and Ben-Bassat,
Arie and Sariaslani, F. Sima and Huang, Lixuan},
title = {Improved production of p-hydroxycinnamic acid from tyrosine using
a novel thermostable phenylalanine/tyrosine ammonia lyase enzyme},
journal = {Enzyme and Microbial Technology},
year = {2007},
volume = {42},
pages = {58--64},
number = {1},
month = dec,
abstract = {p-Hydroxycinnamic acid (pHCA), which serves as the starting material
for production of a number of industrial chemicals, can be produced
by deamination of tyrosine by phenylalanine/tyrosine ammonia lyase
(PAL/TAL) enzyme. In this study, we characterized the PAL/TAL enzymes
from the red yeast Rhodotorula glutinis (RgTAL) and a novel thermostable
PAL/TAL from the wood rotting fungus, Phanerochaete chrysosporium
(PcTAL). Both enzymes were expressed at ~50% level of total soluble
proteins under the control of the araB promoter. At 25 °C and pH
9.5, the RgTAL enzyme showed kcat and Km values of 0.93 s-1 and 68 [mu]M
for tyrosine and 1.5 s-1 and 126 [mu]M for phenylalanine, while these
values, for PcTAL, at the same pH and at 35 °C, were 1.3 s-1 and
44 [mu]M for tyrosine and 3.3 s-1 and 161 [mu]M for phenylalanine.
The purified PcTAL was thermostable and retained its full activity
at 60 °C for up to 3 h, while RgTAL lost most of its activity at
this temperature. Thermostability of PcTAL allowed increasing the
reaction temperature which, in addition to accelerating the reaction
rate, improved solubility of the tyrosine substrate, thus, allowing
production of significantly higher amounts of pHCA.},
issn = {0141-0229},
keywords = {Tyrosine ammonia lyase (TAL), Phenylalanine ammonia lyase (PAL), Trans-p-hydroxycinnamic
acid (p-coumarate, pHCA), Protein expression, Arabinose-inducible
promoter (araB), Thermostable enzyme},
url = {http://www.sciencedirect.com/science/article/B6TG1-4PFDDR3-3/2/63eb1369500afb5f94f9b250dd2c1ff3}
}
@ARTICLE{Yabuki2007,
author = {Yabuki, Nami and Sakata, Kiyoaki and Yamasaki, Tomoaki and Terashima,
Hiromichi and Mio, Toshiyuki and Miyazaki, Youko and Fujii, Toshihiko
and Kitada, Kunio},
title = {Gene amplification and expression in lung cancer cells with acquired
paclitaxel resistance},
journal = {Cancer Genetics and Cytogenetics},
year = {2007},
volume = {173},
pages = {1--9},
number = {1},
month = feb,
abstract = {A paclitaxel-resistant subline was generated from the non-small lung
cancer cell line NCI-H460 by stepwise selection in paclitaxel from
0.032 to 250 nmol/L. The resulting subline, designated NCI-H460/PTX250,
showed 792-fold resistance against paclitaxel compared with the parental
cell line NCI-H460. The chemosensitivity analysis revealed the cross-resistance
phenotype against various anticancer drugs including docetaxel, vinblastine,
and doxorubicin, but not against camptotecin, cisplatin, and 5-fluorouracil.
The addition of 5 [mu]mol/L verapamil or reversin 121 reversed the
resistance against paclitaxel, vinblastine, and doxorubicin. The
gene expression profile, examined using oligonucleotide microarrays,
demonstrated that the expression of 332 and 342 genes was significantly
increased and decreased, respectively, in NCI-H460/PTX250 compared
with NCI-H460. The most highly upregulated gene was MDR1/ABCB1 with
a 1,092-fold increase. The overexpression was confirmed at the protein
level by Western blot and flow cytometry analyses. The copy number
profile, examined using microarray-based comparative genomic hybridization,
revealed amplification of the q11.21~q21.12 region on chromosome
7. In particular, the entire q21.12 region displayed 11- to 13-fold
higher copy number in NCI-H460/PTX250 than in NCI-H460. Most of the
genes within the region were highly expressed, and the increased
expression of these genes could be explained by the amplification
in the gene copy number. However, the increase in MDR1/ABCB1 expression
greatly exceeded the genomic copy number increase of the gene, suggesting
the existence of one or more additional factors, such as transcriptional
enhancement or mRNA stabilization, associated with the elevated MDR1/ABCB1
expression. In conclusion, both chromosomal region-specific copy
number amplification and gene-specific activation are probably involved
in the overexpression of MDR1/ABCB1, resulting in acquisition of
the drug resistance phenotype in NCI-H460/PTX250.},
issn = {0165-4608},
url = {http://www.sciencedirect.com/science/article/B6T53-4N02H4S-3/2/fa8090a447a57d16cd7d5be4a09f708f}
}
@ARTICLE{Yacoubian2008,
author = {Yacoubian, Talene A. and Cantuti-Castelvetri, Ippolita and Bouzou,
Bérengère and Asteris, Georgios and McLean, Pamela J. and Hyman,
Bradley T. and Standaert, David G.},
title = {Transcriptional dysregulation in a transgenic model of Parkinson
disease},
journal = {Neurobiology of Disease},
year = {2008},
volume = {29},
pages = {515--528},
number = {3},
month = mar,
abstract = {Alpha-synuclein has been implicated in Parkinson disease, yet the
mechanism by which alpha-synuclein causes cell injury is not understood.
Using a transgenic mouse model, we evaluated the effect of alpha-synuclein
overexpression on gene expression in the substantia nigra. Nigral
mRNA from wild type and alpha-synuclein transgenic mice was analyzed
using Affymetrix gene arrays. At 3 months, before pathological changes
are apparent, we observed modest alterations in gene expression.
However, nearly 200 genes were altered in expression at 9 months,
when degenerative changes are more apparent. Functional genomic analysis
revealed that the genes altered at 9 months were predominantly involved
in gene transcription. As in human Parkinson disease, gene expression
changes in the transgenic model were also modulated by gender. These
data demonstrate that alterations of gene expression are widespread
in this animal model, and suggest that transcriptional dysregulation
may be a disease mechanism that can be targeted therapeutically.},
issn = {0969-9961},
keywords = {Parkinson disease, Alpha-synuclein, Microarray, Substantia nigra,
Laser capture microdissection, Mouse, Transcription},
url = {http://www.sciencedirect.com/science/article/B6WNK-4R7J81D-3/2/a795c09ef2cb608045f4bc57cfde0a83}
}
@ARTICLE{Yadav2009,
author = {Yadav, Ram Kishor and Girke, Thomas and Pasala, Sumana and Xie, Mingtang
and Reddy, G. Venugopala},
title = {Gene expression map of the Arabidopsis shoot apical meristem stem
cell niche},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {4941--4946},
number = {12},
month = mar,
abstract = {Despite the central importance of stem cells in plant growth and development,
the molecular signatures associated with them have not been revealed.
Shoot apical meristems (SAMs) harbor a small set of stem cells located
at the tip of each plant and they are surrounded by several million
differentiating cells. This imposes a major limitation in isolating
pure populations of stem cells for genomic analyses. We have developed
a system to isolate pure populations of distinct cell types of the
SAMs, including stem cells. We have used this system to profile gene
expression from 4 different cell samples of SAMs. The cell sample-specific
gene expression profiling has resulted in a high-resolution gene
expression map to reveal gene expression networks specific to individual
spatial domains of SAMs. We demonstrate that the cell sample-specific
expression profiling is sensitive in identifying rare transcripts
expressed in a few specific subsets of cells of SAMs. Our extensive
RNA in situ analysis reveals that the expression map can be used
as a predictive tool in analyzing the spatial expression patterns
of genes and it has led to the identification of unique gene expression
patterns within the SAMs. Furthermore, our work reveals an enrichment
of DNA repair and chromatin modification pathways in stem cells suggesting
that maintenance of genome stability and flexible chromatin may be
crucial for stem cell function. The gene expression map should guide
future reverse genetics experiments, high-resolution analyses of
cell-cell communication networks and epigenetic modifications.},
url = {http://www.pnas.org/cgi/content/abstract/106/12/4941}
}
@ARTICLE{Yagi2011,
author = {Yagi, Takuya and Ito, Daisuke and Okada, Yohei and Akamatsu, Wado
and Nihei, Yoshihiro and Yoshizaki, Takahito and Yamanaka, Shinya
and Okano, Hideyuki and Suzuki, Norihiro},
title = {Modeling familial Alzheimer's disease with induced pluripotent stem
cells},
journal = {Hum. Mol. Genet.},
year = {2011},
volume = {20},
pages = {4530-4539},
number = {23},
abstract = {Alzheimer's disease (AD) is the most common form of age-related dementia,
characterized by progressive memory loss and cognitive disturbance.
Mutations of presenilin 1 (PS1) and presenilin 2 (PS2) are causative
factors for autosomal-dominant early-onset familial AD (FAD). Induced
pluripotent stem cell (iPSC) technology can be used to model human
disorders and provide novel opportunities to study cellular mechanisms
and establish therapeutic strategies against various diseases, including
neurodegenerative diseases. Here we generate iPSCs from fibroblasts
of FAD patients with mutations in PS1 (A246E) and PS2 (N141I), and
characterize the differentiation of these cells into neurons. We
find that FAD-iPSC-derived differentiated neurons have increased
amyloid {beta}42 secretion, recapitulating the molecular pathogenesis
of mutant presenilins. Furthermore, secretion of amyloid {beta}42
from these neurons sharply responds to {gamma}-secretase inhibitors
and modulators, indicating the potential for identification and validation
of candidate drugs. Our findings demonstrate that the FAD-iPSC-derived
neuron is a valid model of AD and provides an innovative strategy
for the study of age-related neurodegenerative diseases.},
doi = {10.1093/hmg/ddr394},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/20/23/4530.pdf},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/20/23/4530}
}
@ARTICLE{Yagi2003,
author = {Yagi, Tomohito and Morimoto, Akira and Eguchi, Mariko and Hibi, Shigeyoshi
and Sako, Masahiro and Ishii, Eiichi and Mizutani, Shuki and Imashuku,
Shinsaku and Ohki, Misao and Ichikawa, Hitoshi},
title = {Identification of a gene expression signature associated with pediatric
AML prognosis},
journal = {Blood},
year = {2003},
volume = {102},
pages = {1849--1856},
number = {5},
month = sep,
abstract = {Most patients with acute myeloid leukemia (AML) enter complete remission
(CR) after treatment with chemotherapy, but a large number of them
experience relapse with resistant disease. To identify genes that
are associated with their prognoses, we analyzed gene expression
in 54 pediatric patients with AML using an oligonucleotide microarray
that contained 12 566 probe sets. A supervised approach using the
Student t test selected a prognostic set of 35 genes, some of which
are associated with the regulation of cell cycle and apoptosis. Most
of these genes had not previously been reported to be associated
with prognosis and were not correlated with morphologically classified
French-American-British (FAB) subtypes or with karyotypes. These
results indicate the existence of prognosis-associated genes that
are independent of cell lineage and cytogenetic abnormalities, and
they can provide therapeutic direction for individual risk-adapted
therapy for pediatric AML patients.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/5/1849}
}
@ARTICLE{Yakar2009,
author = {Yakar, Shoshana and Rosen, Clifford J. and Bouxsein, Mary L. and
Sun, Hui and Mejia, Wilson and Kawashima, Yuki and Wu, Yingjie and
Emerton, Kelly and Williams, Valerie and Jepsen, Karl and Schaffler,
Mitchell B. and Majeska, Robert J. and Gavrilova, Oksana and Gutierrez,
Mariana and Hwang, David and Pennisi, Patricia and Frystyk, Jan and
Boisclair, Yves and Pintar, John and Jasper, Hector and Domene, Horacio
and Cohen, Pinchas and Clemmons, David and LeRoith, Derek},
title = {Serum complexes of insulin-like growth factor-1 modulate skeletal
integrity and carbohydrate metabolism},
journal = {FASEB J},
year = {2009},
volume = {23},
pages = {709--719},
number = {3},
month = mar,
abstract = {Serum insulin-like growth factor (IGF) -1 is secreted mainly by the
liver and circulates bound to IGF-binding proteins (IGFBPs), either
as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5
and an acid-labile subunit (ALS). The purpose of this study was to
genetically dissect the role of IGF-1 circulatory complexes in somatic
growth, skeletal integrity, and metabolism. Phenotypic comparisons
of controls and four mouse lines with genetic IGF-1 deficits--liver-specific
IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout,
and a triply deficient LID/ALSKO/BP3 line--produced several novel
findings. 1) All deficient strains had decreased serum IGF-1 levels,
but this neither predicted growth potential or skeletal integrity
nor defined growth hormone secretion or metabolic abnormalities.
2) IGF-1 deficiency affected development of both cortical and trabecular
bone differently, effects apparently dependent on the presence of
different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted
in increased linear growth. In summary, each IGF-1 complex constituent
appears to play a distinct role in determining skeletal phenotype,
with different effects on cortical and trabecular bone compartments.--Yakar,
S., Rosen, C. J., Bouxsein, M. L., Sun, H., Mejia, W., Kawashima,
Y., Wu, Y., Emerton, K., Williams, V., Jepsen, K., Schaffler, M.
B., Majeska, R. J., Gavrilova, O., Gutierrez, M., Hwang, D., Pennisi,
P., Frystyk, J., Boisclair, Y., Pintar, J., Jasper, H., Domene, H.,
Cohen, P., Clemmons, D., LeRoith, D. Serum complexes of insulin-like
growth factor-1 modulate skeletal integrity and carbohydrate metabolism.},
url = {http://www.fasebj.org/cgi/content/abstract/23/3/709}
}
@ARTICLE{Yakirevich2007,
author = {Yakirevich, Evgeny and Jackson, Cynthia L. and Meitner, Patricia
A. and MacKenzie, Dolores and Tavares, Rose and Robinson-Bostom,
Leslie and DeLellis, Ronald A. and Resnick, Murray B.},
title = {Analysis of T-Cell Clonality Using Laser Capture Microdissection
and High-Resolution Microcapillary Electrophoresis},
journal = {J. Mol. Diagn.},
year = {2007},
volume = {9},
pages = {490--497},
number = {4},
month = sep,
abstract = {Identification of clonal lymphocytic populations by polymerase chain
reaction may be difficult in cases with scant cellular infiltrates
or those with a heterogeneous population of cells. Here, we assessed
the diagnostic utility of laser capture microdissection (LCM) and
high-resolution microcapillary electrophoresis in the analysis of
clonality of small biopsy specimens. Clonality was determined in
24 cases: five reactive tonsils, five reactive lymph nodes, six inflammatory
skin lesions, and eight T-cell lymphomas. CD3-positive T lymphocytes
were captured by LCM from paraffinized immunohistochemically stained
sections. Genomic DNA was analyzed for T-cell receptor-{gamma} gene
rearrangement by polymerase chain reaction followed by high-resolution
microcapillary electrophoresis with the DNA 500 LabChip and the Agilent
Bioanalyzer. In the reactive specimens, T-cell receptor-{gamma} polymerase
chain reaction revealed monoclonal bands when 10 to 1000 cells were
captured. This pattern changed to polyclonal when higher numbers
of cells were microdissected (2000 to 10,000 cells). In contrast,
lymphoma cells were consistently monoclonal whether low or high numbers
were microdissected. Microcapillary electrophoresis coupled with
LCM facilitated clonality analysis in equivocal cases. In two of
eight lymphoma cases, LCM revealed diagnostic monoclonal bands, whereas
routine T-cell receptor-{gamma} assessment of whole tissue sections
with 10% polyacrylamide gel electrophoresis demonstrated only minor
clonal bands. We conclude that clonality determined by LCM is cell
number-dependent. Biopsy specimens containing low numbers of reactive
polyclonal T cells may produce pseudomonoclonal bands and therefore
should be interpreted with great caution.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/9/4/490}
}
@ARTICLE{Yakovlev2011,
author = {Igor A. Yakovlev and Daniel K.A. Asante and Carl Gunnar Fossdal and
Olavi Junttila and Øystein Johnsen},
title = {Differential gene expression related to an epigenetic memory affecting
climatic adaptation in Norway spruce},
journal = {Plant Science},
year = {2011},
volume = {180},
pages = {132 - 139},
number = {1},
note = {Plant and Microbe Adaptation to Cold},
abstract = {In Norway spruce, the temperature during zygotic embryogenesis appears
to adjust an adaptive epigenetic memory in the progeny that may regulate
bud phenology and cold acclimation. Conditions colder than normal
advance the timing whilst temperatures above normal delay the onset
of these processes and altered performance is long lasting in progeny
with identical genetic background.
As a step toward unraveling the molecular mechanism behind an epigenetic
memory, transcriptional analysis was performed on seedlings from
seeds of six full-sib families produced at different embryogenesis
temperature–cold (CE) vs warm (WE) under long and short day conditions.
We prepared two suppressive subtracted cDNA libraries, forward and
reverse, representing genes predominantly expressed in plants from
seeds obtained after CE and WE embryogenesis following short day
treatment (inducing bud set).
Sequencing and annotation revealed considerable differences in the
transcriptome of WE versus CE originated plants. By using qRT-PCR
we studied the expression patterns of 32 selected candidate genes
chosen from subtractive cDNA libraries analysis and nine siRNA pathways
genes by a direct candidate approach. Eight genes, two transposons
related genes, three with no match to Databases sequences and three
genes from siRNA pathways (PaDCL1 and 2, PaSGS3) showed differential
expression in progeny from CE and WE correlated with the family phenotypic
differences. These findings may contribute to our understanding of
the epigenetic mechanisms underlying adaptive changes acquired during
embryogenesis.},
doi = {10.1016/j.plantsci.2010.07.004},
issn = {0168-9452},
keywords = {Epigenetic},
url = {http://www.sciencedirect.com/science/article/pii/S0168945210001913}
}
@ARTICLE{Yakovlev2010,
author = {Yakovlev, Igor A. and Fossdal, Carl Gunnar and Johnsen, Øystein},
title = {MicroRNAs, the epigenetic memory and climatic adaptation in Norway
spruce},
journal = {New Phytologist},
year = {2010},
volume = {187},
pages = {1154--1169},
number = {4},
abstract = {Summary * •Norway spruce expresses a temperature-dependent epigenetic
memory from the time of embryo development, which thereafter influences
the timing bud phenology. MicroRNAs (miRNAs)are endogenous small
RNAs, exerting epigenetic gene regulatory impacts. We have tested
for their presence and differential expression. * •We prepared
concatemerized small RNA libraries from seedlings of two full-sib
families, originated from seeds developed in a cold and warm environment.
One family expressed distinct epigenetic effects while the other
not. We used available plant miRNA query sequences to search for
conserved miRNAs and from the sequencing we found novel ones; the
miRNAs were monitored using relative real time-PCR. * •Sequencing
identified 24 novel and four conserved miRNAs. Further screening
of the conserved miRNAs confirmed the presence of 16 additional miRNAs.
Most of the miRNAs were targeted to unknown genes. The expression
of seven conserved and nine novel miRNAs showed significant differences
in transcript levels in the full-sib family showing distinct epigenetic
difference in bud set, but not in the nonresponding full-sib family.
Putative miRNA targets were studied. * •Norway spruce contains
a set of conserved miRNAs as well as a large proportion of novel
nonconserved miRNAs. The differentially expression of specific miRNAs
indicate their putative participation in the epigenetic regulation.},
issn = {1469-8137},
keywords = {bud set, epigenetic, microRNA, miRNA expression, reverse-transcription
polymerase chain reaction (RT-PCR)},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-8137.2010.03341.x}
}
@ARTICLE{Yakovlev2008,
author = {Yakovlev, Igor A. and Hietala, Ari M. and Steffenrem, Arne and Solheim,
Halvor and Fossdal, Carl Gunnar},
title = {Identification and analysis of differentially expressed Heterobasidion
parviporum genes during natural colonization of Norway spruce stems},
journal = {Fungal Genetics and Biology},
year = {2008},
volume = {45},
pages = {498--513},
number = {4},
month = apr,
abstract = {To identify differentially expressed genes of the white-rot fungus
Heterobasidion parviporum, two cDNA libraries were constructed using
suppressive subtraction hybridization (SSH) technique with RNA extracted
from an advanced stage of decay area and from colonization front
next to the reaction zone of the stem of a mature Norway spruce naturally
colonized by the fungus. Besides several cytochrome P450s and hypothetical
proteins with unknown function, the SSH libraries constructed contained,
among others, genes involved in basic cellular processes, and lignin
and cellulose degradation. To examine the role of selected candidate
genes for each functional group, three trees, each colonized by a
different genotype of the pathogen and showing a variable degree
of wood decay, were used for real-time RT-PCR profiling of candidate
genes. In the decay transition areas the study revealed activity
centers that showed remarkable similarity in the transcript profiles
of the monitored genes.},
issn = {1087-1845},
keywords = {White rot, Decay, Reaction zone, Suppression subtractive hybridization,
Gene expression, Quantitative real-time PCR},
url = {http://www.sciencedirect.com/science/article/B6WFV-4PYYV0X-2/2/69a50af585d0bbb4731975aff9a9d444}
}
@ARTICLE{Yaku2008,
author = {Yaku, Hidenobu and Yukimasa, Tetsuo and Nakano, Shu-ichi and Sugimoto,
Naoki and Oka, Hiroaki},
title = {Design of allele-specific primers and detection of the human ABO
genotyping to avoid the pseudopositive problem},
journal = {ELECTROPHORESIS},
year = {2008},
volume = {29},
pages = {4130--4140},
number = {20},
abstract = {Abstract 10.1002/elps.200800097.abs PCR experiments using DNA primers
forming mismatch pairing with template lambda DNA at the 3′ end
were carried out in order to develop allele-specific primers capable
of detecting SNP in genomes without generating pseudopositive amplification
products, and thus avoiding the so-called pseudopositive problem.
Detectable amounts of PCR products were obtained when primers forming
a single or two mismatch pairings at the 3′ end were used. In particular,
3′ terminal A/C or T/C (primer/template) mismatches tended to allow
PCR amplification to proceed, resulting in pseudopositive results
in many cases. While less PCR product was observed for primers forming
three terminal mismatch pairings, target DNA sequences were efficiently
amplified by primers forming two mismatch pairings next to the terminal
G/C base pairing. These results indicate that selecting a primer
having a 3′ terminal nucleotide that recognizes the SNP nucleotide
and the next two nucleotides that form mismatch pairings with the
template sequence can be used as an allele-specific primer that eliminates
the pseudopositive problem. Trials with the human ABO genes demonstrated
that this primer design is also useful for detecting a single base
pair difference in gene sequences with a signal-to-noise ratio of
at least 45.},
issn = {1522-2683},
keywords = {Allele-specific primer, Human ABO gene, Pseudopositive problem, SNP,
3′ terminal mismatch pairings},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200800097}
}
@ARTICLE{Yalcin2010,
author = {Yalcin, M. and Dyskin, E. and Lansing, L. and Bharali, D. J. and
Mousa, S. S. and Bridoux, A. and Hercbergs, A. H. and Lin, H. Y.
and Davis, F. B. and Glinsky, G. V. and Glinskii, A. and Ma, J. and
Davis, P. J. and Mousa, S. A.},
title = {Tetraiodothyroacetic Acid (Tetrac) and Nanoparticulate Tetrac Arrest
Growth of Medullary Carcinoma of the Thyroid},
journal = {J. Clin. Endocrinol. Metab.},
year = {2010},
volume = {95},
pages = {1972--1980},
number = {4},
month = apr,
abstract = {Context: Tetraiodothyroacetic acid (tetrac) blocks angiogenic and
tumor cell proliferation actions of thyroid hormone initiated at
the cell surface hormone receptor on integrin {alpha}v{beta}3. Tetrac
also inhibits angiogenesis initiated by vascular endothelial growth
factor and basic fibroblast growth factor. Objective: We tested antiangiogenic
and antiproliferative efficacy of tetrac and tetrac nanoparticles
(tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants
in the chick chorioallantoic membrane (CAM) and h-MTC xenografts
in the nude mouse. Design: h-MTC cells were implanted in the CAM
model (n = 8 per group); effects of tetrac and tetrac NP at 1 {micro}g/CAM
were determined on tumor angiogenesis and tumor growth after 8 d.
h-MTC cells were also implanted sc in nude mice (n = 6 animals per
group), and actions on established tumor growth of unmodified tetrac
and tetrac NP ip were determined. Results: In the CAM, tetrac and
tetrac NP inhibited tumor growth and tumor-associated angiogenesis.
In the nude mouse xenograft model, established 450-500 mm3 h-MTC
tumors were reduced in size over 21 d by both tetrac formulations
to less than the initial cell mass (100 mm3). Tumor tissue hemoglobin
content of xenografts decreased by 66% over the course of administration
of each drug. RNA microarray and quantitative real-time PCR of tumor
cell mRNAs revealed that both tetrac formulations significantly induced
antiangiogenic thrombospondin 1 and apoptosis activator gene expression.
Conclusions: Acting via a cell surface receptor, tetrac and tetrac
NP inhibit growth of h-MTC cells and associated angiogenesis in CAM
and mouse xenograft models.},
url = {http://jcem.endojournals.org/cgi/content/abstract/95/4/1972}
}
@ARTICLE{Yalcindag2011,
author = {Yalcindag, Erhan and Elguero, Eric and Arnathau, Celine and Durand,
Patrick and Akiana, Jean and Anderson, Timothy J. and Aubouy, Agnes
and Balloux, Francois and Besnard, Patrick and Bogreau, Herve and
Carnevale, Pierre and D'Alessandro, Umberto and Fontenille, Didier
and Gamboa, Dionicia and Jombart, Thibaut and Le Mire, Jacques and
Leroy, Eric and Maestre, Amanda and Mayxay, Mayfong and Menard, Didier
and Musset, Lise and Newton, Paul N. and Nkoghe, Dieudonne and Noya,
Oscar and Ollomo, Benjamin and Rogier, Christophe and Veron, Vincent
and Wide, Albina and Zakeri, Sedigheh and Carme, Bernard and Legrand,
Eric and Chevillon, Christine and Ayala, Francisco J. and Renaud,
Francois and Prugnolle, Franck},
title = {Multiple independent introductions of Plasmodium falciparum in South
America},
journal = {PNAS},
year = {2011},
pages = {1119058109},
abstract = {The origin of Plasmodium falciparum in South America is controversial.
Some studies suggest a recent introduction during the European colonizations
and the transatlantic slave trade. Other evidence--archeological
and genetic--suggests a much older origin. We collected and analyzed
P. falciparum isolates from different regions of the world, encompassing
the distribution range of the parasite, including populations from
sub-Saharan Africa, the Middle East, Southeast Asia, and South America.
Analyses of microsatellite and SNP polymorphisms show that the populations
of P. falciparum in South America are subdivided in two main genetic
clusters (northern and southern). Phylogenetic analyses, as well
as Approximate Bayesian Computation methods suggest independent introductions
of the two clusters from African sources. Our estimates of divergence
time between the South American populations and their likely sources
favor a likely introduction from Africa during the transatlantic
slave trade.},
doi = {10.1073/pnas.1119058109},
eprint = {http://www.pnas.org/cgi/reprint/1119058109v1.pdf},
url = {http://www.pnas.org/cgi/content/abstract/1119058109v1}
}
@ARTICLE{Yamada2007,
author = {Yamada, Daisuke And Ohuchida, Kenoki And Mizumoto, Kazuhiro And Ohhashi,
Seiji And Yu, Jun And Egami, Takuya And Fujita, Hayato And Nagai,
Eishi And Tanaka, Masao},
title = {Increased Expression of ADAM 9 and ADAM 15 mRNA in Pancreatic Cancer},
journal = {Anticancer Res},
year = {2007},
volume = {27},
pages = {793--799},
number = {2},
month = mar,
abstract = {Background: A disintegrin and metalloproteases (ADAMs) comprise a
multifunctional family of membrane-anchored proteins. ADAM 9 and
ADAM 15 are involved in cell migration and invasion. Expression of
ADAM 9 and ADAM 15 was reported to be altered in several types of
cancer. Materials and Methods: Quantitative real-time reverse transcription-polymerase
chain reaction was performed to measure the expression of ADAM 9
mRNA in bulk pancreatic tissues. Results showed no significant difference
in the expression of ADAM 9 mRNA between pancreatic cancer and non-neoplastic
pancreas. Primary cultured pancreatic fibroblasts also expressed
ADAM 9 mRNA. Therefore, a laser microdissection and pressure catapulting
technique was employed to isolate cancer cells from tumor tissues.
The expression of ADAM 9 and ADAM 15 mRNA was measured in microdissected
samples (cancer cells, n=11; normal epithelial cells, n=13 for ADAM
9; cancer cells, n=9; normal epithelial cells, n=9 for ADAM 15).
Results: Pancreatic cancer cells expressed significantly higher levels
of ADAM 9 and ADAM 15 mRNA than did normal pancreatic epithelial
cells (p=0.016 for ADAM 9; p=0.004 for ADAM 15). Conclusion: ADAM
9 and ADAM 15 are involved in pancreatic cancer. Microdissection-based
analysis appears to be indispensable for the accurate analysis of
the expression of certain ADAM family members in pancreatic cancer.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/27/2/793}
}
@ARTICLE{Yamada2009,
author = {Yamada, Hirotomo and Uenishi, Rie and Suzuki, Kaoru and Koizumi,
Shinji},
title = {Cadmium-induced alterations of gene expression in human cells},
journal = {Environmental Toxicology and Pharmacology},
year = {2009},
volume = {28},
pages = {61--69},
number = {1},
month = jul,
abstract = {We have reported the changes in gene expression in human HeLa cells
exposed to a low concentration (5 [mu]M) of Cd. In the present study,
cells exposed to a higher concentration of Cd were analyzed using
a DNA microarray with 9182 human cDNA probes, in an attempt to obtain
a comprehensive view on the biological effects of Cd. After a 6 h
exposure to 50 [mu]M Cd, 48 genes were up-regulated 2.5-fold or greater
and 14 genes were down-regulated to 40% or less. Marked up-regulation
of genes coding for metallothioneins, anti-oxidant proteins, and
heat shock proteins was observed. Cd appeared to repress cell proliferation
by modulating genes involved in multiple pathways. Cd also affected
a number of genes related to apoptosis. Interestingly, it appeared
that a series of genes were regulated to accelerate the intrinsic
pathway of apoptosis, while others were directed to suppress the
extrinsic pathway. Of these, rapid and transient induction of the
TR3 gene was noted as a possible key process in Cd-induced apoptosis.
Effects on several genes that may reflect mechanistic backgrounds
of Cd toxicity were also observed. The present study disclosed a
complex pleiotypic response of human cells to Cd, which was composed
of a variety of changes in gene expression directed to defense, growth
arrest, recovery from damage, apoptosis and so on.},
issn = {1382-6689},
keywords = {Cadmium, DNA microarray, HeLa cells, Apoptosis, Growth arrest},
url = {http://www.sciencedirect.com/science/article/B6T6D-4VPV5FV-2/2/ee8e14cdaa2cc000ef57ceb94fd1de85}
}
@ARTICLE{Yamada2008,
author = {Yamada, Kazutaka and Terahara, Takeshi and Kurata, Shinya and Yokomaku,
Toyokazu and Tsuneda, Satoshi and Harayama, Shigeaki},
title = {Retrieval of entire genes from environmental DNA by inverse PCR with
pre-amplification of target genes using primers containing locked
nucleic acids},
journal = {Environmental Microbiology},
year = {2008},
volume = {10},
pages = {978--987},
number = {4},
abstract = {Summary We had been unsuccessful to amplify desired nucleotide sequences
from various environmental DNA samples by using the inverse polymerase
chain reaction (IPCR) technique, most probably because the copy numbers
of target DNA sequences had been quite low. To enrich the target
DNA sequences prior to IPCR, a rolling-circle amplification was used
with a site-specific primer containing locked nucleic acids (LNAs).
This pre-amplified IPCR (PAI-PCR) method increased the sensitivity
of PCR almost 10Â 000 times compared with the standard IPCR in model
experiments using Escherichia coli. We then applied the PAI-PCR method
to isolate glycosyl hydrolase genes from DNAs extracted from vermiform
appendixes of horses and termite guts. The flanking sequences of
the target genes were amplified and cloned successfully using PAI-PCR,
whereas standard IPCR resulted in no amplification.},
issn = {1462-2920},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-2920.2007.01518.x}
}
@ARTICLE{Yamada2011a,
author = {Yamada, Mitsuhiro and Gomez, John C. and Chugh, Pauline E. and Lowell,
Clifford A. and Dinauer, Mary C. and Dittmer, Dirk P. and Doerschuk,
Claire M.},
title = {Interferon-{gamma} Production by Neutrophils during Bacterial Pneumonia
in Mice},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2011},
volume = {183},
pages = {1391--1401},
number = {10},
month = may,
abstract = {Rationale: Neutrophils are usually the first circulating leukocytes
to respond during bacterial pneumonia. Their expression of oxidants,
proteases, and other mediators present in granules is well documented,
but their ability to produce mediators through transcription and
translation after migration to an inflammatory site has been appreciated
only more recently. Interferon (IFN)-{gamma} is a cytokine with many
functions important in host defense and immunity. Objectives: To
examine the expression and function of IFN-{gamma} in bacterial pneumonias.
Methods: IFN-{gamma} mRNA and protein were measured in digests of
mouse lungs with 24-hour bacterial pneumonia. Bacterial clearance
was studied with IFN-{gamma}-deficient mice. Measurements and Main
Results: Streptococcus pneumoniae and Staphylococcus aureus each
induce expression of IFN-{gamma} mRNA and protein by neutrophils
by 24 hours. Only neutrophils that have migrated into pneumonic tissue
produce IFN-{gamma}. Deficiency of Hck/Fgr/Lyn, Rac2, or gp91phox
prevents IFN-{gamma} production. IFN-{gamma} enhances bacterial clearance
and is required for formation of neutrophil extracellular traps.
In contrast, Pseudomonas aeruginosa and Escherichia coli induce production
of IFN-{gamma} mRNA but not protein. During pneumonia induced by
E. coli but not S. pneumoniae, neutrophils produce microRNAs that
target the 3' untranslated region of the IFN-{gamma} gene. Conclusions:
S. pneumoniae and S. aureus, but not P. aeruginosa and E. coli, induce
emigrated neutrophils to produce IFN-{gamma} within 24 hours. Hck/Fgr/Lyn,
Rac2, and NADPH oxidase are required for IFN-{gamma} production.
IFN-{gamma} facilitates bacterial clearance at least in part through
regulating formation of neutrophil extracellular traps. Differential
expression by neutrophils of microRNAs that target the 3' untranslated
region of the IFN-{gamma} gene may contribute to the pathogen-specific
regulation of translation.},
comment = {10.1164/rccm.201004-0592OC},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/183/10/1391}
}
@ARTICLE{Yamada2008a,
author = {Yamada, Misa and Shida, Yoshiko and Takahashi, Kou and Tanioka, Toshihiro
and Nakano, Yasuko and Tobe, Takashi and Yamada, Mitsuhiko},
title = {Prg1 is regulated by the basic helix-loop-helix transcription factor
Math2},
journal = {Journal of Neurochemistry},
year = {2008},
volume = {106},
pages = {2375--2384},
number = {6},
abstract = {Abstract Math2 (NEX-1/NeuroD6) is a member of the basic helix-loop-helix
transcription factor family and is involved in neuronal differentiation
and maturation. In this study, we identified the genes targeted by
Math2 using DNA microarrays and cultured rat cortical cells transfected
with Math2. Of the genes regulated by Math2, we focused on plasticity-related
gene 1 (Prg1). Prg1 expression induced by Math2 was confirmed in
cultured rat cortical cells and PC12 cells analyzed by real-time
quantitative PCR. In the promoter region of rat Prg1, we identified
four E-boxes [designated −E1 to −E4 (CANNTG)] recognized by the
basic helix-loop-helix transcription factor. Using chromatin immunoprecipitation
assays, we found that Math2 directly bound to at least one of these
E-boxes. The Prg1 reporter assay showed that −E1 was critical for
the regulation of Math2-mediated Prg1 expression. Investigation of
the functional roles of Math2 and Prg1 in PC12 cells revealed that
72Â h after transfection with either Math2 or Prg1, neurite length
and number were significantly induced. Co-transfection with Prg1-siRNA
completely inhibited Math2-mediated morphological changes. Our results
suggest that Math2 directly regulates Prg1 expression and that the
Math2–Prg1 cascade plays an important role in neurite outgrowth
in PC12 cells.},
issn = {1471-4159},
keywords = {GeneChip®, Math2, neuronal plasticity, plasticity-related gene 1},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2008.05579.x}
}
@ARTICLE{Yamada2011b,
author = {Yamada, Takeshi and Kikuchi, Kae and Yamauchi, Toshihiro and Shiraishi,
Koji and Ito, Tsukasa and Okabe, Satoshi and Hiraishi, Akira and
Ohashi, Akiyoshi and Harada, Hideki and Kamagata, Yoichi and Nakamura,
Kazunori and Sekiguchi, Yuji},
title = {Ecophysiology of Uncultured Filamentous Anaerobes Belonging to the
Phylum KSB3 That Cause Bulking in Methanogenic Granular Sludge},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {2081--2087},
number = {6},
month = mar,
abstract = {A filamentous bulking of a methanogenic granular sludge caused by
uncultured filamentous bacteria of the candidate phylum KSB3 in an
upflow anaerobic sludge blanket (UASB) system has been reported.
To characterize the physiological traits of the filaments, a polyphasic
approach consisting of rRNA-based activity monitoring of the KSB3
filaments using the RNase H method and substrate uptake profiling
using microautoradiography combined with fluorescence in situ hybridization
(MAR-FISH) was conducted. On the basis of rRNA-based activity, the
monitoring of a full-scale UASB reactor operated continuously revealed
that KSB3 cells became active and predominant (up to 54% of the total
16S rRNA) in the sludge when the carbohydrate loading to the system
increased. Batch experiments with a short incubation of the sludge
with maltose, glucose, fructose, and maltotriose at relatively low
concentrations (approximately 0.1 mM) in the presence of yeast extract
also showed an increase in KSB3 rRNA levels under anaerobic conditions.
MAR-FISH confirmed that the KSB3 cells took up radioisotopic carbons
from [14C]maltose and [14C]glucose under the same incubation conditions
in the batch experiments. These results suggest that one of the important
ecophysiological characteristics of KSB3 cells in the sludge is carbohydrate
degradation in wastewater and that high carbohydrate loadings may
trigger an outbreak of KSB3 bacteria, causing sludge bulking in UASB
systems.},
comment = {10.1128/AEM.02475-10},
url = {http://aem.asm.org/cgi/content/abstract/77/6/2081}
}
@ARTICLE{Yamada2010,
author = {Yamada, Takashi and Satoh, Souichi and Ishikawa, Hiroki and Fujiwara,
Akiko and Kawasaki, Takeru and Fujie, Makoto and Ogata, Hiroyuki},
title = {A jumbo phage infecting the phytopathogen Ralstonia solanacearum
defines a new lineage of the Myoviridae family},
journal = {Virology},
year = {2010},
volume = {398},
pages = {135--147},
number = {1},
month = mar,
abstract = {[phi]RSL1 is a jumbo myovirus stably and lytically infecting the phytopathogenic
bacterium Ralstonia solanacearum. In this study, we investigate the
infection cycle of [phi]RSL1 and provide a genomic, proteomic and
transcriptomic view of this phage. Its 231-kbp genome sequence showed
many genes lacking detectable homologs in the current databases and
was vastly different from previously studied phage genomes. In addition
to these orphan proteins, [phi]RSL1 was found to encode several enzymes
that are unique among known viruses. These include enzymes for the
salvage pathway of NAD+ and for the biosynthetic pathways of lipid,
carbohydrate and homospermidine. A chitinase-like protein was found
to be a potential lysis enzyme. Our proteomics analysis suggests
that [phi]RSL1 virions contain at least 25 distinct proteins. We
identified six of them including a tail sheath protein and a topoisomerase
IB by N-terminal sequencing. Based on a DNA microarray analysis,
we identified two transcription patterns.},
issn = {0042-6822},
keywords = {Jumbo bacteriophage, Ralstonia solanacearum, Genomic analysis, Proteomic
analysis, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6WXR-4Y0TDNC-2/2/536979a97ae3f5a3a3827e9a986797b3}
}
@ARTICLE{Yamada2008b,
author = {Yamada, Yasuhide and Arao, Tokuzo and Gotoda, Takuji and Taniguchi,
Hirokazu and Oda, Ichiro and Shirao, Kuniaki and Shimada, Yasuhiro
and Hamaguchi, Tetsuya and Kato, Ken and Hamano, Tetsutaro and Koizumi,
Fumiaki and Tamura, Tomohide and Saito, Daizo and Shimoda, Tadakazu
and Saka, Makoto and Fukagawa, Takeo and Katai, Hitoshi and Sano,
Takeshi and Sasako, Mitsuru and Nishio, Kazuto},
title = {Identification of prognostic biomarkers in gastric cancer using endoscopic
biopsy samples},
journal = {Cancer Science},
year = {2008},
volume = {99},
pages = {2193--2199},
number = {11},
abstract = {Endoscopic biopsy prior to chemotherapy provides an opportunity for
studying biomarkers to predict the overall survival in gastric cancer
patients. This prospective study was performed to identify prognostic
biomarkers in patients with unresected gastric cancer. Fifty-nine
cases of chemotherapy-naive metastatic gastric cancer were enrolled
in this study. A microarray analysis was performed using 40 biopsy
samples to identify candidate genes whose expressions might be correlated
with the overall survival. After adjusting for clinical covariates
based on a multivariate analysis, the identified genes were validated
using real-time reverse transcription polymerase chain reaction (RT-PCR)
analysis in 19 independent validation samples. Ninety-eight candidate
genes whose expression levels were significantly correlated with
the overall survival were identified using a microarray analysis
based on a proportional hazards model (PÂ <Â 0.005). Multivariate
analysis was performed to assess 10 of these genes, and the results
yielded a statistical significance level for DACH1 and PDCD6. We
further evaluated these two genes in independent samples using real-time
RT-PCR and found that lower mRNA expression levels of PDCD6 were
correlated significantly with a poor overall survival. We identified
PDCD6 as a prognostic biomarker in patients with unresected gastric
cancer using endoscopic biopsy samples. Our PCR-based single gene
prediction strategy successfully predicted the overall survival and
may lead to a better understanding of this disease subgroup. (Cancer
Sci 2008; 99: 2193–2199)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2008.00935.x}
}
@ARTICLE{Yamada2011,
author = {Yamada, Yasutoshi and Enokida, Hideki and Kojima, Satoko and Kawakami,
Kazumori and Chiyomaru, Takeshi and Tatarano, Shuichi and Yoshino,
Hirofumi and Kawahara, Kazuya and Nishiyama, Kenryu and Seki, Naohiko
and Nakagawa, Masayuki},
title = {MiR-96 and miR-183 detection in urine serve as potential tumor markers
of urothelial carcinoma: correlation with stage and grade, and comparison
with urinary cytology},
journal = {Cancer Science},
year = {2011},
volume = {102},
pages = {522--529},
number = {3},
abstract = {A new diagnostic marker for urothelial carcinoma (UC) is needed to
avoid painful cystoscopy during the initial diagnosis and follow-up
period. However, the current urine markers are useless because of
the low sensitivities and specificities for UC detection. MiR-96
and miR-183 were differentially upregulated microRNA in our previous
microRNA screening for UC. The expression levels of miR-96 and miR-183
in the urine samples were significantly higher in 100 UC than in
healthy controls (miR-96, PÂ =Â 0.0059; and miR-183, PÂ =Â 0.0044).
The receiver-operating characteristic curve analyses demonstrated
that each microRNA had good sensitivity and specificity for distinguishing
UC patients from non-UC patients (miR-96, 71.0% and 89.2%; and miR-183,
74.0% and 77.3%). Our cohort included 78 UC patients who had undergone
urinary cytology. MiR-96 was positively detected in 27 of 44 patients
who had had a “negative� urinary cytology diagnosis. We combined
the miR-96 detection data with the urinary cytology data, and diagnosed
61 of 78 cases as UC; sensitivity rose from 43.6% to 78.2%. We found
significant stepwise increases in miR-96 and miR-183 expression with
advancing tumor grade (miR-96, PÂ =Â 0.0057; and miR-183, PÂ =Â 0.0036)
and pathological stage (miR-96, PÂ =Â 0.0332; and miR-183, PÂ =Â 0.0117).
The expression levels of the microRNA were significantly lower in
urine collected after surgery (miR-96, PÂ =Â 0.0241; and miR-183,
PÂ =Â 0.0045). In conclusion, miR-96 and miR-183 in urine are promising
tumor markers for UC. In particular, miR-96 may be a good diagnostic
marker in combination with urinary cytology. (Cancer Sci 2011; 102:
522–529)},
doi = {10.1111/j.1349-7006.2010.01816.x},
issn = {1349-7006},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1349-7006.2010.01816.x}
}
@ARTICLE{Yamada2008c,
author = {Yamada, Yuko and Tian, Jane and Yang, Yanqin and Cutler, Roy G. and
Wu, Tinghuai and Telljohann, Richard S. and Mattson, Mark P. and
Handa, James T.},
title = {Oxidized low density lipoproteins induce a pathologic response by
retinal pigmented epithelial cells},
journal = {Journal of Neurochemistry},
year = {2008},
volume = {105},
pages = {1187--1197},
number = {4},
abstract = {Abstract The accumulation of apolipoprotein B100 lipoproteins in Bruch
membrane is an early event thought to promote age-related macular
degeneration (AMD). Immunohistochemistry using an anti-oxidized low
density lipoprotein antibody on 10 AMD specimens showed staining
in Bruch membrane including basal deposits, a marker of AMD. To determine
whether retinal pigmented epithelial cells develop a pathologic phenotype
after interaction with lipoproteins, ARPE-19 cells were exposed to
low density lipoproteins (LDL) or oxidized LDLs (oxLDL). Analysis
using the Affymetrix U133 Plus 2.0 (Affymetrix, Inc., Santa Clara,
CA, USA) gene chip showed physiological and pathological transcriptional
responses after LDL and oxLDL treatment, respectively. LDL induced
a down-regulation of cholesterol biosynthesis genes while oxLDL induced
transcriptional alterations in genes related to lipid metabolism,
oxidative stress, inflammation and apoptosis. Electrospray mass spectrometry
showed that oxLDL, but not LDL induced large cellular increases of
sphingomyelin, ceramides, and cholesteryl esters. With TUNEL labeling,
oxLDL caused 14.6% apoptosis compared to <1% after LDL. Addition
of an inhibitor of sphingomyelin synthase inhibited this apoptosis
by 41%. These data support the hypothesis that oxidized lipoproteins
are one trigger for initiating early events in the pathogenesis of
AMD.},
issn = {1471-4159},
keywords = {age-related macular degeneration, apoptosis, ceramides, cholesterol,
oxidized low density lipoproteins, retinal pigmented epithelium},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2008.05211.x}
}
@ARTICLE{Yamagiwa2004,
author = {Yamagiwa, Yoko and Marienfeld, Carla and Meng, Fanyin and Holcik,
Martin and Patel, Tushar},
title = {Translational Regulation of X-Linked Inhibitor of Apoptosis Protein
by Interleukin-6: A Novel Mechanism of Tumor Cell Survival},
journal = {Cancer Res.},
year = {2004},
volume = {64},
pages = {1293--1298},
number = {4},
month = feb,
abstract = {Interleukin-6 (IL-6) is a pleiotropic cytokine with diverse biological
effects. IL-6 has been implicated in autocrine signaling pathways
promoting tumor progression and chemoresistance in some human tumors.
However, the mechanisms by which IL-6 modulates these responses are
unknown. Aberrant apoptosis has been implicated as a fundamental
mechanism of chemotherapeutic resistance. Thus, we investigated whether
IL-6 alters the expression of apoptosis regulatory proteins as a
mechanism of drug resistance. We provide evidence that IL-6 rapidly
phosphorylates the translation initiation factor eukaryotic initiation
factor-4E and triggers antiapoptotic responses in cholangiocarcinoma
cells. Reduction of cellular eukaryotic initiation factor-4E by RNA
interference decreases IL-6-induced effects on cytotoxic drug-induced
caspase activation and apoptosis. Furthermore, IL-6 increases expression
of the endogenous X-linked inhibitor of apoptosis protein expression
by translation at an internal ribosome entry site. Our findings that
IL-6 translationally regulates X-linked inhibitor of apoptosis protein
expression reveal a novel mechanism by which IL-6 mediates tumor
cell survival that may be targeted therapeutically to decrease tumor
progression and chemoresistance.},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/4/1293}
}
@ARTICLE{Yamagiwa2003,
author = {Yamagiwa, Yoko and Marienfeld, Carla and Tadlock, Laura and Patel,
Tushar},
title = {Translational regulation by p38 mitogen-activated protein kinase
signaling during human cholangiocarcinoma growth},
journal = {Hepatology},
year = {2003},
volume = {38},
pages = {158--166},
number = {1},
abstract = {Abstract 10.1002/hep.510380121.abs The p38 mitogen-activated protein
kinase (MAPK) signaling pathway is aberrantly expressed and maintains
transformed cell growth in malignant human cholangiocytes. Because
cell growth requires and is intimately related to protein synthesis,
our aims were to assess the effect of p38 MAPK signaling on protein
synthesis during growth of malignant human cholangiocytes. Inhibition
of p38 MAPK activity during mitogenic stimulation decreased protein
synthesis rates and tumor cell xenograft growth in nude mice. Altered
protein synthesis resulted from decreased translational efficiency
with impaired initiation of translation. Mitogenic stimulation resulted
in phosphorylation of the eukaryotic initiation factor (eIF)-4E.
Inhibition of p38 MAPK signaling or functional dysregulation of translation
by small interfering double-stranded RNA (siRNA) to eIF-4E decreased
anchorage-independent growth of malignant cholangiocytes. In conclusion,
these studies identify a relationship between p38 MAPK activity and
the regulation of protein synthesis during human cholangiocarcinoma
growth. As protein synthesis is intimately linked to cell growth,
dysregulation of translation initiation is a mechanism by which cellular
p38 MAPK signaling participates in growth regulation of malignant
cholangiocytes.},
issn = {1527-3350},
publisher = {W.B. Saunders},
url = {http://dx.doi.org/10.1053/jhep.2003.50257}
}
@ARTICLE{Yamaguchi2010a,
author = {Yamaguchi, Hirotaka and Fukuoka, Hiroyuki and Arao, Tomohito and
Ohyama, Akio and Nunome, Tsukasa and Miyatake, Koji and Negoro, Satomi},
title = {Gene expression analysis in cadmium-stressed roots of a low cadmium-accumulating
solanaceous plant, Solanum torvum},
journal = {J. Exp. Bot.},
year = {2010},
volume = {61},
pages = {423--437},
number = {2},
month = jan,
abstract = {Solanum torvum Sw. cv. Torubamubiga (TB) is a low cadmium (Cd)-accumulating
plant. To elucidate the molecular mechanisms of the Cd acclimation
process in TB roots, transcriptional regulation was analysed in response
to mild Cd treatment: 0.1 {micro}M CdCl2 in hydroponic solution.
A unigene set consisting of 6296 unigene sequences was constructed
from 18 816 TB cDNAs. The distribution of functional categories was
similar to tomato, while 330 unigenes were suggested to be TB specific.
For expression profiling, the SuperSAGE method was adapted for use
with Illumina sequencing technology. Expression tag libraries were
constructed from Cd-treated (for 3 h, 1 d, and 3 d) and untreated
roots, and 34 269 species of independent tags were collected. Moreover,
6237 tags were ascribed to the TB or eggplant (aubergine) unigene
sequences. Time-course changes were examined, and 2049 up- and 2022
down-regulated tags were identified. Although no tags annotated to
metal transporter genes were significantly regulated, a tag annotated
to AtFRD3, a xylem-loading citrate transporter, was down-regulated.
In addition to induction of heavy metal chaperone proteins, antioxidative
and sulphur-assimilating enzymes were induced, confirming that oxidative
stress developed even using a mild Cd concentration. Rapid repression
of dehydration-related transcription factors and aquaporin isoforms
suggests that dehydration stress is a potential constituent of Cd-induced
biochemical impediments. These transcriptional changes were also
confirmed by real-time reverse transcription-PCR. Further additions
of TB unigene sequences and functional analysis of the regulated
tags will reveal the molecular basis of the Cd acclimation process,
including the low Cd-accumulating characteristics of TB.},
url = {http://jxb.oxfordjournals.org/cgi/content/abstract/61/2/423}
}
@ARTICLE{Yamaguchi2010,
author = {Yamaguchi, Hiroshi and Kojima, Takashi and Ito, Tatsuya and Kimura,
Yasutoshi and Imamura, Masafumi and Son, Seiichi and Koizumi, Jun-ichi
and Murata, Masaki and Nagayama, Minoru and Nobuoka, Takayuki and
Tanaka, Satoshi and Hirata, Koichi and Sawada, Norimasa},
title = {Transcriptional Control of Tight Junction Proteins via a Protein
Kinase C Signal Pathway in Human Telomerase Reverse Transcriptase-Transfected
Human Pancreatic Duct Epithelial Cells},
journal = {Am. J. Pathol.},
year = {2010},
volume = {177},
pages = {698--712},
number = {2},
month = aug,
abstract = {In human pancreatic cancer, integral membrane proteins of tight junction
claudins are abnormally regulated, making these proteins promising
molecular diagnostic and therapeutic targets. However, the regulation
of claudin-based tight junctions remains unknown not only in the
pancreatic cancer cells but also in normal human pancreatic duct
epithelial (HPDE) cells. To investigate the regulation of tight junction
molecules including claudins in normal HPDE cells, we introduced
the human telomerase reverse transcriptase (hTERT) gene into HPDE
cells in primary culture. The hTERT-transfected HPDE (hTERT-HPDE)
cells were positive for the pancreatic duct epithelial markers such
as CK7, CK19, and carbonic anhydrase isozyme 2 and expressed epithelial
tight junction molecules claudin-1, -4, -7 and, -18, occludin, JAM-A,
ZO-1, ZO-2, and tricellulin. By treatment with fetal bovine serum
or 12-O-tetradecanoylphorbol 13-acetate (TPA), the tight junction
molecules were up-regulated at the transcriptional level via a protein
kinase C (PKC) signal pathway. A PKC-{alpha} inhibitor, Go6976, prevented
up-regulation of claudin-4 by TPA. Furthermore, a PKC-{delta} inhibitor,
rottlerin, prevented up-regulation of claudin-7, occludin, ZO-1,
and ZO-2 by TPA. By GeneChip analysis, up-regulation of the transcription
factor ELF3 was observed in both fetal bovine serum- and TPA-treated
cells. Treatment with small interfering RNAs of ELF3 prevented up-regulation
of claudin-7 by TPA. These data suggest that tight junctions of normal
HPDE cells were at least in part regulated via a PKC signal pathway
by transcriptional control.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/2/698}
}
@ARTICLE{Yamaguchi2006,
author = {Yamaguchi, N. and Ohba, H. and Nasu, M.},
title = {Simple detection of small amounts of Pseudomonas cells in milk by
using a microfluidic device},
journal = {Letters in Applied Microbiology},
year = {2006},
volume = {43},
pages = {631--636},
number = {6},
abstract = {Abstract Aims:  Flow cytometry offers rapid and reliable analyses
of bacteria in milk. However, a flow cytometer is relatively expensive
and operation is rather complicated for an unskilled operator. We
applied flow cytometry using a microfluidic device (on-chip flow
cytometry) in detection of small amounts of milk-spoiling bacteria.
Methods and Results: Pseudomonas cells in milk were in situ hybridized
with Cy5-labelled probe specific for Pseudomonas spp. under optimized
condition. Numbers of Pseudomonas cells in the stationary phase and
in the starved state determined by on-chip flow cytometry were compared
with those determined by conventional plate counting, and on-chip
flow cytometry detected targeted cells in milk that were undetectable
as colony forming units(CFU) on Standards Methods Agar. Conclusions: 
The contamination in milk with fewer than 10 CFU ml−1 of targeted
cells in starved state was detectable with simple procedure (0·5 h
milk-clearing, 1 h fixation, 2 h hybridization and 0·5 h on-chip
flow cytometry following 12Â h enrichment of cells). Significance
and Impact of the Study:  On-chip flow cytometry following fluorescence
in situ hybridization could be applicable to simple detection of
milk-spoiling bacteria.},
issn = {1472-765X},
keywords = {fluorescence in situ hybridization, food contamination, microbial
monitoring, milk, on-chip flow cytometry, Pseudomonas spp},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1472-765X.2006.02013.x}
}
@ARTICLE{Yamaguchi2004,
author = {Yamaguchi, Yuji and Itami, Satoshi and Watabe, Hidenori and Yasumoto,
Ken-ichi and Abdel-Malek, Zalfa A. and Kubo, Tateki and Rouzaud,
Francois and Tanemura, Atsushi and Yoshikawa, Kunihiko and Hearing,
Vincent J.},
title = {Mesenchymal-epithelial interactions in the skin: increased expression
of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth
and differentiation},
journal = {J. Cell Biol.},
year = {2004},
volume = {165},
pages = {275--285},
number = {2},
month = apr,
abstract = {We investigated whether or not the topographic regulation of melanocyte
differentiation is determined by mesenchymal-epithelial interactions
via fibroblast-derived factors. The melanocyte density in palmoplantar
human skin (i.e., skin on the palms and the soles) is five times
lower than that found in nonpalmoplantar sites. Palmoplantar fibroblasts
significantly suppressed the growth and pigmentation of melanocytes
compared with nonpalmoplantar fibroblasts. Using cDNA microarray
analysis, fibroblasts derived from palmoplantar skin expressed high
levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling
pathway), whereas nonpalmoplantar fibroblasts expressed higher levels
of DKK3. Transfection studies revealed that DKK1 decreased melanocyte
function, probably through {beta}-catenin-mediated regulation of
microphthalmia-associated transcription factor activity, which in
turn modulates the growth and differentiation of melanocytes. Thus,
our results provide a basis to explain why skin on the palms and
the soles is generally hypopigmented compared with other areas of
the body, and might explain why melanocytes stop migrating in the
palmoplantar area during human embryogenesis.},
url = {http://jcb.rupress.org/cgi/content/abstract/165/2/275}
}
@ARTICLE{Yamaguchi2008,
author = {Yamaguchi, Yuji and Passeron, Thierry and Hoashi, Toshihiko and Watabe,
Hidenori and Rouzaud, Francois and Yasumoto, Ken-ichi and Hara, Takahiko
and Tohyama, Chiharu and Katayama, Ichiro and Miki, Toru and Hearing,
Vincent J.},
title = {Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting
Wnt/{beta}-catenin signaling in keratinocytes},
journal = {FASEB J},
year = {2008},
volume = {22},
pages = {1009--1020},
number = {4},
month = apr,
abstract = {The epidermis (containing primarily keratinocytes and melanocytes)
overlies the dermis (containing primarily fibroblasts) of human skin.
We previously reported that dickkopf 1 (DKK1) secreted by fibroblasts
in the dermis elicits the hypopigmented phenotype of palmoplantar
skin due to suppression of melanocyte function and growth via the
regulation of two important signaling factors, microphthalmia-associated
transcription factor (MITF) and {beta}-catenin. We now report that
treatment of keratinocytes with DKK1 increases their proliferation
and decreases their uptake of melanin and that treatment of reconstructed
skin with DKK1 induces a thicker and less pigmented epidermis. DNA
microarray analysis revealed many genes regulated by DKK1, and several
with critical expression patterns were validated by reverse transcriptase-polymerase
chain reaction and Western blotting. DKK1 induced the expression
of keratin 9 and {alpha}-Kelch-like ECT2 interacting protein ({alpha}KLEIP)
but down-regulated the expression of {beta}-catenin, glycogen synthase
kinase 3{beta}, protein kinase C, and proteinase-activated receptor-2
(PAR-2), which is consistent with the expression patterns of those
proteins in human palmoplantar skin. Treatment of reconstructed skin
with DKK1 reproduced the expression patterns of those key proteins
observed in palmoplantar skin. These findings further elucidate why
human skin is thicker and paler on the palms and soles than on the
trunk through topographical and site-specific differences in the
secretion of DKK1 by dermal fibroblasts that affects the overlying
epidermis.--Yamaguchi, Y., Passeron, T., Hoashi, T., Watabe, H.,
Rouzaud, F., Yasumoto, K., Hara, T., Tohyama, C., Katayama, I., Miki,
T., Hearing, V. J. Dickkopf 1 (DKK1) regulates skin pigmentation
and thickness by affecting Wnt/{beta}-catenin signaling in keratinocytes.},
url = {http://www.fasebj.org/cgi/content/abstract/22/4/1009}
}
@ARTICLE{Yamaji-Kegan2010,
author = {Yamaji-Kegan, Kazuyo and Su, Qingning and Angelini, Daniel J. and
Myers, Allen C. and Cheadle, Chris and Johns, Roger A.},
title = {Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM{alpha}) Increases
Lung Inflammation and Activates Pulmonary Microvascular Endothelial
Cells via an IL-4-Dependent Mechanism},
journal = {J. Immunol.},
year = {2010},
volume = {185},
pages = {5539--5548},
number = {9},
month = nov,
abstract = {Hypoxia-induced mitogenic factor (HIMF), also known as found in inflammatory
zone 1 and resistin-like molecule {alpha}, belongs to a novel class
of cysteine-rich secreted proteins. It exhibits mitogenic and chemotactic
properties during pulmonary hypertension-associated vascular remodeling,
as well as fibrogenic properties during pulmonary fibrosis. HIMF
expression in the lung was reported to be regulated by Th2 cytokines
(IL-4 and IL-13) via the transcription factor STAT6 pathway in a
bleomycin-induced pulmonary fibrosis model. However, in this study,
we found that in the hypoxia-induced pulmonary hypertension model,
lung HIMF expression is increased in IL-4 and STAT6 knockout (KO)
mice to the same degree as in wild-type (WT) mice, suggesting that
induction of HIMF expression does not require Th2 regulation in this
model. We also found that HIMF-induced proliferative activity, hypertrophy,
collagen, and extracellular matrix deposition in the pulmonary arteries
are significantly less in IL-4 KO mice than in WT mice. In addition,
HIMF-induced production of angiogenic factors/chemokines, such as
vascular endothelial growth factor, MCP-1, and stromal-derived factor-1,
in the lung resident cells, as well as macrophage infiltration, were
significantly suppressed in the lungs of IL-4 KO mice. We also show
that IL-4 was significantly increased in the lungs of HIMF-treated
WT mice. Our in vitro studies using pulmonary microvascular endothelial
cells revealed that HIMF stimulated cell proliferation, vascular
endothelial growth factor expression, and MCP-1 production in a manner
that is dependent on the IL-4/IL-4R{alpha} system. These findings
suggest that IL-4 signaling may play a significant role in HIMF-induced
lung inflammation and vascular remodeling.},
url = {http://www.jimmunol.org/cgi/content/abstract/185/9/5539}
}
@ARTICLE{Yamakawa2010,
author = {Yamakawa, Hiromoto and Hakata, Makoto},
title = {Atlas of Rice Grain Filling-Related Metabolism under High Temperature:
Joint Analysis of Metabolome and Transcriptome Demonstrated Inhibition
of Starch Accumulation and Induction of Amino Acid Accumulation},
journal = {Plant Cell Physiol.},
year = {2010},
volume = {51},
pages = {795--809},
number = {5},
month = may,
abstract = {High temperature impairs grain filling by inhibiting the deposition
of storage materials such as starch and protein. To comprehend its
impact on grain filling metabolism in rice (Oryza sativa), levels
of metabolites and transcripts related to central pathways of metabolism
were simultaneously determined in developing caryopses exposed to
high temperature (33{degrees}C/28{degrees}C) and a control temperature
(25{degrees}C/20{degrees}C) during the milky stage. A capillary electrophoresis-based
metabolomic analysis revealed that high temperature increased the
accumulation of sucrose and pyruvate/ oxaloacetate-derived amino
acids and decreased levels of sugar phosphates and organic acids
involved in glycolysis/gluconeogenesis and the tricarboxylic acid
(TCA) cycle, respectively. A transcriptomic analysis using a whole
genome-covering microarray unraveled the possible metabolic steps
causing the shortage of storage materials under the elevated temperature.
Starch deposition might be impaired by down-regulation of sucrose
import/degradation and starch biosynthesis, and/or up-regulation
of starch degradation as well as inefficient ATP production by an
inhibited cytochrome respiration chain, as indicated by the response
of gene expression to high temperature. Amino acid accumulation might
be attributed to the heat-stable import of amino acids into the caryopsis
and/or repression of protein synthesis especially the tRNA charging
step under high temperature. An atlas showing the effect of high
temperature on levels of metabolites and gene expression in the central
metabolic pathways is presented.},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/51/5/795}
}
@ARTICLE{Yamakawa2007,
author = {Yamakawa, Hiromoto and Hirose, Tatsuro and Kuroda, Masaharu and Yamaguchi,
Takeshi},
title = {Comprehensive Expression Profiling of Rice Grain Filling-Related
Genes under High Temperature Using DNA Microarray},
journal = {Plant Physiology},
year = {2007},
volume = {144},
pages = {258--277},
number = {1},
month = may,
abstract = {To elucidate the effect of high temperature on grain-filling metabolism,
developing rice (Oryza sativa) Nipponbare' caryopses were exposed
to high temperature (33{degrees}C/28{degrees}C) or control temperature
(25{degrees}C/20{degrees}C) during the milky stage. Comprehensive
gene screening by a 22-K DNA microarray and differential hybridization,
followed by expression analysis by semiquantitative reverse transcription-PCR,
revealed that several starch synthesis-related genes, such as granule-bound
starch synthase I (GBSSI) and branching enzymes, especially BEIIb,
and a cytosolic pyruvate orthophosphate dikinase gene were down-regulated
by high temperature, whereas those for starch-consuming {alpha}-amylases
and heat shock proteins were up-regulated. Biochemical analyses of
starch showed that the high temperature-ripened grains contained
decreased levels of amylose and long chain-enriched amylopectin,
which might be attributed to the repressed expression of GBSSI and
BEIIb, respectively. SDS-PAGE and immunoblot analysis of storage
proteins revealed decreased accumulation of 13-kD prolamin, which
is consistent with the diminished expression of prolamin genes under
elevated temperature. Ripening under high temperature resulted in
the occurrence of grains with various degrees of chalky appearance
and decreased weight. Among them, severely chalky grains contained
amylopectin enriched particularly with long chains compared to slightly
chalky grains, suggesting that such alterations of amylopectin structure
might be involved in grain chalkiness. However, among high temperature-tolerant
and sensitive cultivars, alterations of neither amylopectin chain-length
distribution nor amylose content were correlated to the degree of
grain chalkiness, but rather seemed to be correlated to grain weight
decrease, implying different underlying mechanisms for the varietal
difference in grain chalkiness. The possible metabolic pathways affected
by high temperature and their relevance to grain chalkiness are discussed.},
url = {http://www.plantphysiol.org/cgi/content/abstract/144/1/258}
}
@ARTICLE{Yamaleyeva2007,
author = {Yamaleyeva, Liliya M. and Gallagher, Patricia E. and Vinsant, Sharon
and Chappell, Mark C.},
title = {Discoordinate regulation of renal nitric oxide synthase isoforms
in ovariectomized mRen2.Lewis rats},
journal = {Am J Physiol Regulatory Integrative Comp Physiol},
year = {2007},
volume = {292},
pages = {R819--826},
number = {2},
month = feb,
abstract = {Estrogen depletion markedly exacerbates hypertension in female congenic
mRen2.Lewis rats, a model of tissue renin overexpression. Because
estrogen influences nitric oxide synthase (NOS) and NO may exert
differential effects on blood pressure, the present study investigated
the functional expression of NOS isoforms in the kidney of ovariectomized
(OVX) mRen2.Lewis rats. OVX-mRen2.Lewis exhibited an increase in
systolic blood pressure (SBP) of 171 {+/-} 5 vs. 141 {+/-} 7 mmHg
(P < 0.01) for intact littermates. Renal cortical mRNA and protein
levels for endothelial NOS (eNOS) were reduced 50-60% (P < 0.05)
and negatively correlated with blood pressure. In contrast, cortical
neuronal NOS (nNOS) mRNA and protein levels increased 100 to 300%
(P < 0.05). In the OVX kidney, nNOS immunostaining was more evident
in the macula densa, cortical tubules, and the medullary collecting
ducts compared with the intact group. To determine whether the increase
in renal nNOS expression constitutes a compensatory response to the
reduction in renal eNOS, we treated both intact and OVX mRen2.Lewis
rats with the selective nNOS inhibitor L-VNIO from 11 to 15 wk of
age. The nNOS inhibitor reduced blood pressure in the OVX group (185
{+/-} 3 vs. 151 {+/-} 8 mmHg, P < 0.05), but pressure was not altered
in the intact group (146 {+/-} 4 vs. 151 {+/-} 4 mmHg). In summary,
exacerbation of blood pressure in the OVX mRen2.Lewis rats was associated
with the discoordinate regulation of renal NOS isoforms. Estrogen
sensitivity in this congenic strain may involve the influence of
NO through the regulation of both eNOS and nNOS.},
url = {http://ajpregu.physiology.org/cgi/content/abstract/292/2/R819}
}
@ARTICLE{Yamaleyeva2007a,
author = {Yamaleyeva, Liliya M. and Pendergrass, Karl D. and Pirro, Nancy T.
and Gallagher, Patricia E. and Groban, Leanne and Chappell, Mark
C.},
title = {Ovariectomy is protective against renal injury in the high-salt-fed
older mRen2.Lewis rat},
journal = {Am J Physiol Heart Circ Physiol},
year = {2007},
volume = {293},
pages = {H2064--2071},
number = {4},
month = oct,
abstract = {Studies in experimental animals and younger women suggest a protective
role for estrogen; however, clinical trials may not substantiate
this effect in older females. Therefore, the present study assessed
the outcome of ovariectomy in older mRen2.Lewis rats subjected to
a high-salt diet for 4 wk. Intact or ovariectomized (OVX, 15 wk of
age) mRen2.Lewis rats were aged to 60 wk and then placed on a high-salt
(HS, 8% sodium chloride) diet for 4 wk. Systolic blood pressures
were similar between groups [OVX 169 {+/-} 6 vs. Intact 182 {+/-}
7 mmHg; P = 0.22] after the 4-wk diet; however, proteinuria [OVX
0.8 {+/-} 0.2 vs. Intact 11.5 {+/-} 2.6 mg/mg creatinine; P < 0.002,
n = 6], renal interstitial fibrosis, glomerular sclerosis, and tubular
casts were lower in OVX vs. Intact rats. Kidney injury molecule-1
mRNA, a marker of tubular damage, was 53% lower in the OVX HS group.
Independent from blood pressure, OVX HS rats exhibited significantly
lower cardiac (24%) and renal (32%) hypertrophy as well as lower
C-reactive protein (28%). Circulating insulin-like growth factor-I
(IGF-I) levels were not different between the Intact and OVX groups;
however, renal cortical IGF-I mRNA and protein were attenuated in
OVX rats [P < 0.05, n = 6]. We conclude that ovariectomy in the older
female mRen2.Lewis rat conveys protection against salt-dependent
increase in renal injury.},
url = {http://ajpheart.physiology.org/cgi/content/abstract/293/4/H2064}
}
@ARTICLE{Yamamoto2010a,
author = {Yamamoto, Kohji and Ichinose, Hirofumi and Aso, Yoichi and Fujii,
Hiroshi},
title = {Expression analysis of cytochrome P450s in the silkmoth, Bombyx mori},
journal = {Pesticide Biochemistry and Physiology},
year = {2010},
volume = {97},
pages = {1--6},
number = {1},
month = may,
abstract = {Cytochrome P450 (CYP) is a superfamily of proteins involved in a variety
of physiological phenomena. Four cDNAs encoding silkmoth cytochrome
P450 proteins, cyp4M5, cyp6AB4, cyp9A20 and cyp9A22, were cloned
by reverse transcriptase-polymerase chain reaction. These cDNAs showed
identities of 21-24% to each other at the amino acid level. Expression
analysis showed that CYP mRNAs were expressed in a tissue-specific
manner and that expression was developmentally regulated in the fat
body and midgut. We found that various cyps were upregulated in the
fat body after exposure to organophosphorus, neonicotinoid and pyrethroid
insecticides. Our results suggest that over-expressed CYPs can contribute
to insecticide resistance in Lepidopterans.},
issn = {0048-3575},
keywords = {Bombyx mori, Cytochrome P450, Detoxification, Lepidoptera},
url = {http://www.sciencedirect.com/science/article/B6WP8-4XSTD15-7/2/11fbc6162e1f8cb5d92aa15b6afda21c}
}
@ARTICLE{Yamamoto2011,
author = {Yamamoto, K. and Tsuji, Y. and Aso, Y. and Hamasaki, T. and Shirahata,
S. and Katakura, Y.},
title = {Effect of diazinon exposure on antioxidant reactions in the silkmoth,
Bombyx mori},
journal = {Journal of Applied Entomology},
year = {2011},
volume = {135},
pages = {320--325},
number = {4},
abstract = {Abstract We investigated the effects of exposure to diazinon, an organophosphate
insecticide, on the expression of antioxidant and detoxification
factors in the silkmoth. Exposure to diazinon resulted in induction
of mRNA encoding manganese containing superoxide dismutase (SOD)
and omega-class glutathione S-transferases (GST), whereas no changes
were observed in catalase, other class of GST and acetylcholinesterase.
Liquid chromatography showed that the amount of reactive oxygen species
was increased, whereas the amount of glutathione was decreased in
the silkmoth fat body after exposure to diazinon. These results suggest
that SOD and omega-class GSTs can contribute to organophosphate resistance
in Lepidopterans.},
doi = {10.1111/j.1439-0418.2010.01549.x},
issn = {1439-0418},
keywords = {Bombyx mori, antioxidant, diazinon, glutathione, Lepidoptera},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1439-0418.2010.01549.x}
}
@ARTICLE{Yamamoto2009,
author = {Yamamoto, Yoshiyuki and Byerly, Mardi S. and Jackman, William R.
and Jeffery, William R.},
title = {Pleiotropic functions of embryonic sonic hedgehog expression link
jaw and taste bud amplification with eye loss during cavefish evolution},
journal = {Developmental Biology},
year = {2009},
volume = {330},
pages = {200--211},
number = {1},
month = jun,
abstract = {This study addresses the role of sonic hedgehog (shh) in increasing
oral-pharyngeal constructive traits (jaws and taste buds) at the
expense of eyes in the blind cavefish Astyanax mexicanus. In cavefish
embryos, eye primordia degenerate under the influence of hyperactive
Shh signaling. In concert, cavefish show amplified jaw size and taste
bud numbers as part of a change in feeding behavior. To determine
whether pleiotropic effects of hyperactive Shh signaling link these
regressive and constructive traits, shh expression was compared during
late development of the surface-dwelling (surface fish) and cave-dwelling
(cavefish) forms of Astyanax. After an initial expansion along the
midline of early embryos, shh was elevated in the oral-pharyngeal
region in cavefish and later was confined to taste buds. The results
of shh inhibition and overexpression experiments indicate that Shh
signaling has an important role in oral and taste bud development.
Conditional overexpression of an injected shh transgene at specific
times in development showed that taste bud amplification and eye
degeneration are sensitive to shh overexpression during the same
early developmental period, although taste buds are not formed until
much later. Genetic crosses between cavefish and surface fish revealed
an inverse relationship between eye size and jaw size/taste bud number,
supporting a link between oral-pharyngeal constructive traits and
eye degeneration. The results suggest that hyperactive Shh signaling
increases oral and taste bud amplification in cavefish at the expense
of eyes. Therefore, selection for constructive oral-pharyngeal traits
may be responsible for eye loss during cavefish evolution via pleiotropic
function of the Shh signaling pathway.},
issn = {0012-1606},
keywords = {Sonic hedgehog, Oral and jaw development, Taste bud development, Eye
degeneration, Pleiotropy},
url = {http://www.sciencedirect.com/science/article/B6WDG-4VTCM9B-3/2/f10f7eb62751236cca9606c95eb6735a}
}
@ARTICLE{Yamamoto2010,
author = {Yamamoto, Yuta and Tanahashi, Toshihito and Katsuura, Sakurako and
Kurokawa, Ken and Nishida, Kensei and Kuwano, Yuki and Kawai, Tomoko
and Teshima-Kondo, Shigetada and Chikahisa, Sachiko and Tsuruo, Yoshihiro
and Sei, Hiroyoshi and Rokutan, Kazuhito},
title = {Interleukin-18 deficiency reduces neuropeptide gene expressions in
the mouse amygdala related with behavioral change},
journal = {Journal of Neuroimmunology},
year = {2010},
volume = {229},
pages = {129--139},
number = {1-2},
month = dec,
abstract = {In this study, we examined the effects of IL-18 deficiency on behaviors
and gene expression profiles in 6 brain regions. IL-18-/- mice reduced
depressive-like behavior and changed gene expressions predominantly
in the amygdala compared with wild-type mice. Pathway analysis of
the differentially expressed genes ranked behavior as the top-scored
biological function. Of note, the absence of IL-18 decreased Avp,
Hcrt, Oxt, and Pmch mRNA levels and the number of arginine vasopressin-
and oxytocin-positive cells in the amygdala, but not in the hypothalamus.
Our results suggest that IL-18-dependent vasopressinergic and oxytocinergic
circuitry in the amygdala may regulate depressive-like behaviors
in mice.},
issn = {0165-5728},
keywords = {IL-18, Behavior, Microarray, IPA analysis, Vasopressin, Oxytocin},
url = {http://www.sciencedirect.com/science/article/pii/S0165572810003371}
}
@ARTICLE{Yamamoto2009a,
author = {Yamamoto, Yuta and Tanahashi, Toshihito and Kawai, Tomoko and Chikahisa,
Sachiko and Katsuura, Sakurako and Nishida, Kensei and Teshima-Kondo,
Shigetada and Sei, Hiroyoshi and Rokutan, Kazuhito},
title = {Changes in behavior and gene expression induced by caloric restriction
in C57BL/6 mice},
journal = {Physiol Genomics},
year = {2009},
volume = {39},
pages = {227--235},
number = {3},
month = nov,
abstract = {Caloric restriction (CR) is an effective method for prevention of
age-associated diseases as well as overweight and obesity; however,
there is controversy regarding the effects of dieting regimens on
behavior. In this study, we investigated two different dieting regimens:
repeated fasting and refeeding (RFR) and daily feeding of half the
amount of food consumed by RFR mice (CR). CR and RFR mice had an
approximate 20% reduction in food intake compared with control mice.
Open field, light-dark transition, elevated plus maze, and forced
swimming tests indicated that CR, but not RFR, reduced anxiety- and
depressive-like behaviors, with a reduction peak on day 8. Using
a mouse whole genome microarray, we analyzed gene expression in the
prefrontal cortex, amygdala, and hypothalamus. In addition to the
CR-responsive genes commonly modified by RFR and CR, each regimen
differentially changed the expression of distinct genes in each region.
The most profound change was observed in the amygdalas of CR mice:
884 genes were specifically upregulated. Ingenuity pathway analysis
revealed that these 884 genes significantly modified nine canonical
pathways in the amygdala. {alpha}-Adrenergic and dopamine receptor
signalings were the two top-scoring pathways. Quantitative RT-PCR
confirmed the upregulation of six genes in these pathways. Western
blotting confirmed that CR specifically increased dopamine- and cAMP-regulated
phosphoprotein (Darpp-32), a key regulator of dopamine receptor signaling,
in the amygdala. Our results suggest that CR may change behavior
through altered gene expression.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/39/3/227}
}
@ARTICLE{Yamamoto2011a,
author = {Yamamoto, Yusuke and Yoshioka, Yusuke and Minoura, Kaho and Takahashi,
Ryou-u and Takeshita, Fumitaka and Taya, Toshiki and Horii, Reiko
and Fukuoka, Yayoi and Kato, Takashi and Kosaka, Nobuyoshi and Ochiya,
Takahiro},
title = {An integrative genomic analysis revealed the relevance of microRNA
and gene expression for drug-resistance in human breast cancer cells},
journal = {Molecular Cancer},
year = {2011},
volume = {10},
pages = {135},
number = {1},
abstract = {BACKGROUND:Acquisition of drug-resistance in cancer has led to treatment
failure, however, their mechanisms have not been clarified yet. Recent
observations indicated that aberrant expressed microRNA (miRNA) caused
by chromosomal alterations play a critical role in the initiation
and progression of cancer. Here, we performed an integrated genomic
analysis combined with array-based comparative hybridization, miRNA,
and gene expression microarray to elucidate the mechanism of drug-resistance.RESULTS:Through
genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell
line, our results reflect the unique features of drug-resistance,
including MDR1 overexpression via genomic amplification and miRNA-mediated
TP53INP1 down-regulation. Using a gain of function study with 12
miRNAs whose expressions were down-regulated and genome regions were
deleted, we show that miR-505 is a novel tumor suppressive miRNA
and inhibits cell proliferation by inducing apoptosis. We also find
that Akt3, correlate inversely with miR-505, modulates drug sensitivity
in MCF7-ADR.CONCLUSION:These findings indicate that various genes
and miRNAs orchestrate to temper the drug-resistance in cancer cells,
and thus acquisition of drug-resistance is intricately controlled
by genomic status, gene and miRNA expression changes.},
doi = {10.1186/1476-4598-10-135},
issn = {1476-4598},
pubmedid = {22051041},
url = {http://www.molecular-cancer.com/content/10/1/135}
}
@ARTICLE{Yamanaka2009,
author = {Yamanaka, Takeshi and Furukawa, Tomoyo and Matsumoto-Mashimo, Chiho
and Yamane, Kazuyoshi and Sugimori, Chieko and Nambu, Takayuki and
Mori, Naoki and Nishikawa, Hiroyuki and Walker, Clay and Leung, Kai-Poon
and Fukushima, Hisanori},
title = {Gene expression profile and pathogenicity of biofilm-forming Prevotella
intermedia strain 17},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {11},
number = {1},
abstract = {BACKGROUND:Prevotella intermedia (P. intermedia), a gram-negative,
black-pigmented anaerobic rod, has been implicated in the development
of chronic oral infection. P. intermedia strain 17 was isolated from
a chronic periodontitis lesion in our laboratory and described as
a viscous material producing strain. The stock cultures of this strain
still maintain the ability to produce large amounts of viscous materials
in the spent culture media and form biofilm-like structures. Chemical
analyses of this viscous material showed that they were mainly composed
of neutral sugars with mannose constituting 83% of the polysaccharides.
To examine the biological effect of the extracellular viscous materials,
we identified and obtained a naturally-occurring variant strain that
lacked the ability to produce viscous materials in vitro from our
stock culture collections of strain 17, designated as 17-2. We compared
these two strains (strains 17 versus 17-2) in terms of their capacities
to form biofilms and to induce abscess formation in mice as an indication
of their pathogenicity. Further, gene expression profiles between
these two strains in planktonic condition and gene expression patterns
of strain 17 in solid and liquid cultures were also compared using
microarray assays.RESULTS:Strain 17 induced greater abscess formation
in mice as compared to that of the variant. Strain 17, but not 17-2
showed an ability to interfere with the phagocytic activity of human
neutrophils. Expression of several genes which including those for
heat shock proteins (DnaJ, DnaK, ClpB, GroEL and GroES) were up-regulated
two to four-fold with statistical significance in biofilm-forming
strain 17 as compared to the variant strain 17-2. Strain 17 in solid
culture condition exhibited more than eight-fold up-regulated expression
levels of several genes which including those for levanase, extracytoplasmic
function-subfamily sigma factor (sE; putative) and polysialic acid
transport protein (KpsD), as compared to those of strain 17 in liquid
culture media.CONCLUSION:These results demonstrate that the capacity
to form biofilm in P. intermedia contribute to their resistance against
host innate defence responses.},
doi = {10.1186/1471-2180-9-11},
issn = {1471-2180},
pubmedid = {19146705},
url = {http://www.biomedcentral.com/1471-2180/9/11}
}
@ARTICLE{Yamane2012,
author = {Yamane, Takashi and Enokida, Hideki and Hayami, Hiroshi and Kawahara,
Motoshi and Nakagawa, Masayuki},
title = {Genome-wide transcriptome analysis of fluoroquinolone resistance
in clinical isolates of Escherichia coli},
journal = {International Journal of Urology},
year = {2012},
pages = {no--no},
abstract = {Objectives:Â Coincident with their worldwide use, resistance to fluoroquinolones
in Escherichia coli has increased. To identify the gene expression
profiles underlying fluoroquinolone resistance, we carried out genome-wide
transcriptome analysis of fluoroquinolone-sensitive E. coli.Methods:Â
Four fluoroquinolone-sensitive E. coli and five fluoroquinolone-resistant
E. coli clinical isolates were subjected to complementary deoxyribonucleic
acid microarray analysis. Some upregulated genes’ expression was
verified by real-time polymerase chain reaction using 104 E. coli
clinical isolates, and minimum inhibitory concentration tests were
carried out by using their transformants.Results:Â A total of 40
genes were significantly upregulated in fluoroquinolone-resistant
E. coli isolates (P < 0.05). The expression of phage shock protein
operons, which are involved in biofilm formation, was markedly upregulated
in our profile of fluoroquinolone-resistant E. coli. One of the
phage shock protein operons, pspC, was significantly upregulated
in 50 fluoroquinolone-resistant E. coli isolates (P < 0.0001).
The expression of type I fimbriae genes, which are pilus operons
involved in biofilm formation, were markedly downregulated in fluoroquinolone-resistant
E. coli. Deoxyribonucleic acid adenine methyltransferase (dam),
which represses type I fimbriae genes, was significantly upregulated
in the clinical fluoroquinolone-resistant E. coli isolates (P = 0.007).
We established pspC- and dam-expressing E. coli transformants from
fluoroquinolone-sensitive E. coli, and the minimum inhibitory concentration
tests showed that the transformants acquired fluoroquinolone resistance,
suggesting that upregulation of these genes contributes to acquiring
fluoroquinolone resistance.Conclusions:Â Upregulation of psp operones
and dam underlying pilus operons downregulation might be associated
with fluoroquinolone resistance in E. coli.},
doi = {10.1111/j.1442-2042.2011.02933.x},
issn = {1442-2042},
keywords = {Escherichia coli, fluoroquinolone resistance, microarray},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1442-2042.2011.02933.x}
}
@ARTICLE{Yamano2011,
author = {Yamano, Yukio and Shiiba, Masashi and Negoro, Kenji and Nakatani,
Ken and Kasamatsu, Atsushi and Yamatoji, Masanobu and Sakuma, Kentaro
and Ogoshi, Kenji and Iyoda, Manabu and Shinozuka, Keiji and Yokoe,
Hidetaka and Wada, Takeshi and Fujita, Shigeyuki and Iwasawa, Shunichiro
and Takiguchi, Yuichi and Tanzawa, Hideki and Uzawa, Katsuhiro},
title = {Antitumor activity of satraplatin in cisplatin-resistant oral squamous
cell carcinoma cells},
journal = {Head \& Neck},
year = {2011},
volume = {33},
pages = {309--317},
number = {3},
abstract = {Abstract Background.The aim of the current study was to identify the
antitumor activity of satraplatin in paired cisplatin (CDDP)-resistant
oral squamous cell carcinoma (OSCC) cell line and its parental cell
line.Methods.CDDP-resistant (KB-R) cells and parental cells (KB)
pair were used. Viability was assessed using the MTT and clonogenic
assay. Real-time polymerase chain reaction (PCR), glutathione (GSH)
assay, and flow cytometric analysis were used for further assessment.Results.KB-R
cells did not show cross-resistance to satraplatin. The expression
status of almost all transporters was upregulated in the KB-R cells.
There was no difference in the GSH levels between the KB and KB-R
cells. Flow cytometric analysis indicated that with satraplatin the
G2/M phase was arrested in the KB-R cells. KB-R cells contain enriched
side population cells.Conclusion.These data suggested that satraplatin
has antitumor activity against the CDDP-resistant OSCC cells. The
mechanism of cross-resistance to platinum agents seems to be multifactorial.
© 2010 Wiley Periodicals, Inc. Head Neck, 2010},
doi = {10.1002/hed.21445},
issn = {1097-0347},
keywords = {cisplatin, cross-resistance, satraplatin, drug resistance, side population},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hed.21445}
}
@ARTICLE{Yamashita2011,
author = {Yamashita, Riu and Sathira, Nuankanya P. and Kanai, Akinori and Tanimoto,
Kousuke and Arauchi, Takako and Tanaka, Yoshiaki and Hashimoto, Shin-ichi
and Sugano, Sumio and Nakai, Kenta and Suzuki, Yutaka},
title = {Genome-wide characterization of transcriptional start sites in humans
by integrative transcriptome analysis},
journal = {Genome Res.},
year = {2011},
volume = {21},
pages = {775--789},
number = {5},
month = may,
abstract = {We performed a genome-wide analysis of transcriptional start sites
(TSSs) in human genes by multifaceted use of a massively parallel
sequencer. By analyzing 800 million sequences that were obtained
from various types of transcriptome analyses, we characterized 140
million TSS tags in 12 human cell types. Despite the large number
of TSS clusters (TSCs), the number of TSCs was observed to decrease
sharply with increasing expression levels. Highly expressed TSCs
exhibited several characteristic features: Nucleosome-seq analysis
revealed highly ordered nucleosome structures, ChIP-seq analysis
detected clear RNA polymerase II binding signals in their surrounding
regions, evaluations of previously sequenced and newly shotgun-sequenced
complete cDNA sequences showed that they encode preferable transcripts
for protein translation, and RNA-seq analysis of polysome-incorporated
RNAs yielded direct evidence that those transcripts are actually
translated into proteins. We also demonstrate that integrative interpretation
of transcriptome data is essential for the selection of putative
alternative promoter TSCs, two of which also have protein consequences.
Furthermore, discriminative chromatin features that separate TSCs
at different expression levels were found for both genic TSCs and
intergenic TSCs. The collected integrative information should provide
a useful basis for future biological characterization of TSCs.},
comment = {10.1101/gr.110254.110},
url = {http://genome.cshlp.org/cgi/content/abstract/21/5/775}
}
@ARTICLE{Yamauchi2010,
author = {Yamauchi, Daisuke and Nakaya, Kazuhiro and Raveendran, Nithya and
Harbidge, Donald and Singh, Ruchira and Wangemann, Philine and Marcus,
Daniel},
title = {Expression of epithelial calcium transport system in rat cochlea
and vestibular labyrinth},
journal = {BMC Physiology},
year = {2010},
volume = {10},
pages = {1},
number = {1},
abstract = {BACKGROUND:The low luminal Ca2+ concentration of mammalian endolymph
in the inner ear is required for normal hearing and balance. We recently
reported the expression of mRNA for a Ca2+-absorptive transport system
in primary cultures of semicircular canal duct (SCCD) epithelium.RESULTS:We
now identify this system in native vestibular and cochlear tissues
by qRT-PCR, immunoblots and confocal immunolocalization. Transcripts
were found and quantified for several isoforms of epithelial calcium
channels (TRPV5, TRPV6), calcium buffer proteins (calbindin-D9K,
calbindin-D28K), sodium-calcium exchangers (NCX1, NCX2, NCX3) and
plasma membrane Ca2+-ATPase (PMCA1, PMCA2, PMCA3, and PMCA4) in native
SCCD, cochlear lateral wall (LW) and stria vascularis (SV) of adult
rat as well as Ca2+ channels in neonatal SCCD. All components were
expressed except TRPV6 in SV and PMCA2 in SCCD. 1,25-(OH)2vitamin
D3 (VitD) significantly up-regulated transcripts of TRPV5 in SCCD,
calbindin-D9K in SCCD and LW, NCX2 in LW, while PMCA4 in SCCD and
PMCA3 in LW were down-regulated. The expression of TRPV5 relative
to TRPV6 was in the sequence SV > Neonatal SCCD > Adult SCCD > LW
> primary culture SCCD. Expression of TRPV5 protein from primary
culture of SCCD did not increase significantly when cells were incubated
with VitD (1.2 times control; P > 0.05). Immunolocalization showed
the distribution of TRPV5 and TRPV6. TRPV5 was found near the apical
membrane of strial marginal cells and both TRPV5 and TRPV6 in outer
and inner sulcus cells of the cochlea and in the SCCD of the vestibular
system.CONCLUSIONS:These findings demonstrate for the first time
the expression of a complete Ca2+ absorptive system in native cochlear
and vestibular tissues. Regulation by vitamin D remains equivocal
since the results support the regulation of this system at the transcript
level but evidence for control of the TRPV5 channel protein was lacking.},
doi = {10.1186/1472-6793-10-1},
issn = {1472-6793},
pubmedid = {20113508},
url = {http://www.biomedcentral.com/1472-6793/10/1}
}
@ARTICLE{Yamauchi2005,
author = {Yamauchi, Daisuke and Raveendran, Nithya N. and Pondugula, Satyanarayana
R. and Kampalli, Suresh B. and Sanneman, Joel D. and Harbidge, Donald
G. and Marcus, Daniel C.},
title = {Vitamin D upregulates expression of ECaC1 mRNA in semicircular canal},
journal = {Biochemical and Biophysical Research Communications},
year = {2005},
volume = {331},
pages = {1353--1357},
number = {4},
month = jun,
abstract = {The low luminal Ca2+ concentration of mammalian endolymph in the vestibular
labyrinth is required for normal balance. We found transcripts in
primary cultures of semicircular canal duct (SCCD) epithelial cells
from neonatal rats representing a complete transport system for transepithelial
absorption of Ca2+ that is comprised of the epithelial Ca2+ channels
ECaC1 (CaT2, TRPV5) and ECaC2 (CaT1, TRPV6), calbindin (calbindin-D9k,
calbindin-D28k), Na+/Ca2+ exchanger (NCX1, NCX2, and NCX3), and plasma
membrane Ca2+-ATPase (PMCA1, PMCA3, and PMCA4) by RT-PCR. Further,
vitamin D receptor was also expressed in SCCD and it was found by
quantitative RT-PCR that incubation for 24 h with 1,25-dihydroxyvitamin
D3 upregulated the expression of ECaC1, calbindin-D9k, and calbindin-D28k.
These observations provide evidence for the first time of an ECaC-based
Ca2+ transport system in SCCD that could maintain the low Ca2+ concentration
in vestibular endolymph.},
issn = {0006-291X},
keywords = {Semicircular canal duct, Epithelial calcium channel, Calbindin, Na+/Ca2+
exchanger, Plasma membrane Ca2+-ATPase, 1,25-Dihydroxyvitamin D3,
Vitamin D receptor},
url = {http://www.sciencedirect.com/science/article/B6WBK-4G0HTGW-6/2/30cb549ad83420da7ec1132609d0c5ca}
}
@ARTICLE{Yamazaki2011,
author = {Yamazaki, Muneharu and Kim, Kyunghee and Marcus, Daniel},
title = {Sodium selectivity of Reissner's membrane epithelial cells},
journal = {BMC Physiology},
year = {2011},
volume = {11},
pages = {4},
number = {1},
abstract = {BACKGROUND:Sodium absorption by Reissner's membrane is thought to
contribute to the homeostasis of the volume of cochlear endolymph.
It was previously shown that the absorptive transepithelial current
was blocked by amiloride and benzamil. The most commonly-observed
target of these drugs is the epithelial sodium channel (ENaC), which
is composed of the three subunits a-,ß- and ?-ENaC. However, other
less-selective cation channels have also been observed to be sensitive
to benzamil and amiloride. The aim of this study was to determine
whether Reissner's membrane epithelial cells could support parasensory
K+ absorption via amiloride- and benzamil-sensitive electrogenic
pathways.RESULTS:We determined the molecular and functional expression
of candidate cation channels with gene array (GEO GSE6196), RT-PCR,
and whole-cell patch clamp. Transcript expression analysis of Reissner's
membrane detected no amiloride-sensitive acid-sensing ion channels
(ASIC1a, ASIC2a, ASIC2b) nor amiloride-sensitive cyclic-nucleotide
gated channels (CNGA1, CNGA2, CNGA4, CNGB3). By contrast, a-,ß- and
?-ENaC were all previously reported as present in Reissner's membrane.
The selectivity of the benzamil-sensitive cation currents was observed
in whole-cell patch clamp recordings under Cl--free conditions where
cations were the only permeant species. The currents were carried
by Na+ but not K+, and the permeability of Li+ was greater than that
of Na+ in Reissner's membrane. Complete replacement of bath Na+ with
the inpermeable cation NMDG+ led to the same inward current as with
benzamil in a Na+ bath.CONCLUSIONS:These results are consistent with
the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane
mediated by a highly Na+-selective channel that has several key characteristics
in common with aß?-ENaC. The amiloride-sensitive pathway therefore
absorbs only Na+ in this epithelium and does not provide a parasensory
K+ efflux route from scala media.},
doi = {10.1186/1472-6793-11-4},
issn = {1472-6793},
pubmedid = {21284860},
url = {http://www.biomedcentral.com/1472-6793/11/4}
}
@ARTICLE{Yamazawa2010,
author = {Yamazawa, K and Nakabayashi, K and Kagami, M and Sato, T and Saitoh,
S and Horikawa, R and Hizuka, N and Ogata, T},
title = {Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like
phenotype},
journal = {J. Med. Genet.},
year = {2010},
volume = {47},
pages = {782--785},
number = {11},
month = nov,
abstract = {IntroductionWe report a 34-year-old Japanese female with a Silver-Russell
syndrome (SRS)-like phenotype and a mosaic Turner syndrome karyotype
(45,X/46,XX). Methods/ResultsMolecular studies including methylation
analysis of 17 differentially methylated regions (DMRs) on the autosomes
and the XIST-DMR on the X chromosome and genome-wide microsatellite
analysis for 96 autosomal loci and 30 X chromosomal loci revealed
that the 46,XX cell lineage was accompanied by maternal uniparental
isodisomy for all chromosomes (upid(AC)mat), whereas the 45,X cell
lineage was associated with biparentally derived autosomes and a
maternally derived X chromosome. The frequency of the 46,XX upid(AC)mat
cells was calculated as 84% in leukocytes, 56% in salivary cells,
and 18% in buccal epithelial cells. DiscussionThe results imply that
a parthenogenetic activation took place around the time of fertilisation
of a sperm missing a sex chromosome, resulting in the generation
of the upid(AC)mat 46,XX cell lineage by endoreplication of one blastomere
containing a female pronucleus and the 45,X cell lineage by union
of male and female pronuclei. It is likely that the extent of overall
(epi)genetic aberrations exceeded the threshold level for the development
of SRS phenotype, but not for the occurrence of other imprinting
disorders or recessive Mendelian disorders.},
url = {http://jmg.bmj.com/cgi/content/abstract/47/11/782}
}
@ARTICLE{Yan2010a,
author = {Yan, Bo and Neilson, Karen M. and Moody, Sally A.},
title = {Microarray identification of novel downstream targets of FoxD4L1/D5,
a critical component of the neural ectodermal transcriptional network},
journal = {Developmental Dynamics},
year = {2010},
volume = {239},
pages = {3467--3480},
number = {12},
abstract = {Abstract FoxD4L1/D5 is a forkhead transcription factor that functions
as both a transcriptional activator and repressor. FoxD4L1/D5 acts
upstream of several other neural transcription factors to maintain
neural fate, regulate neural plate patterning, and delay the expression
of neural differentiation factors. To identify a more complete list
of downstream genes that participate in these earliest steps of neural
ectodermal development, we carried out a microarray analysis comparing
gene expression in control animal cap ectodermal explants (ACs),
which will form epidermis, to that in FoxD4L1/D5-expressing ACs.
Forty-four genes were tested for validation by RT-PCR of ACs and/or
in situ hybridization assays in embryos; 86% of those genes up-regulated
and 100% of those genes down-regulated in the microarray were altered
accordingly in one of these independent assays. Eleven of these 44
genes are of unknown function, and we provide herein their developmental
expression patterns to begin to reveal their roles in ectodermal
development. Developmental Dynamics 239:3467–3480, 2010. © 2010
Wiley-Liss, Inc.},
doi = {10.1002/dvdy.22485},
issn = {1097-0177},
keywords = {BMP signaling, FGF signaling, cement gland, olfactory placode, epidermis,
Elf-1, FoxD4L1.1, FoxD5},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.22485}
}
@ARTICLE{Yan2011,
author = {Yan, Dong and Stocco, Rino and Sawyer, Nicole and Nesheim, Michael
E. and Abramovitz, Mark and Funk, Colin D.},
title = {Differential Signaling of Cysteinyl Leukotrienes and a Novel Cysteinyl
Leukotriene Receptor 2 (CysLT2) Agonist, N-Methyl-Leukotriene C4,
in Calcium Reporter and {beta} Arrestin Assays},
journal = {Mol. Pharmacol.},
year = {2011},
volume = {79},
pages = {270--278},
number = {2},
month = feb,
abstract = {The cysteinyl leukotrienes (cysLTs) LTC4, LTD4, and LTE4 are lipid
mediators with physiological and pathophysiological functions. They
exert their effects through G protein-coupled receptors (GPCRs),
most notably via CysLT1 and CysLT2 receptor. The roles of the CysLT2
receptor are beginning to emerge. Both LTC4 and LTD4 are potent agonists
for the CysLT2 receptor; however, LTC4 is rapidly converted to LTD4,
which is also the main endogenous ligand for the CysLT1 receptor.
A selective and potent agonist at the CysLT2 receptor would facilitate
studies to discern between receptor subtypes. We show here that N-methyl
LTC4 (NMLTC4), a metabolically stable LTC4 mimetic, is a potent and
selective CysLT2 receptor agonist. Two expression systems were used
to evaluate the functional activity of NMLTC4 at human and/or mouse
CysLT1 and CysLT2 receptors. Through the aequorin cell-based assay
for calcium-coupled GPCRs, NMLTC4 was almost equipotent to LTC4 at
CysLT2 receptors but was the least efficacious at CysLT1 receptors.
In a {beta}-galactosidase-{beta}-arrestin complementation assay,
the human (h) CysLT2 receptor can couple with {beta}-arrestin-2,
and NMLTC4 is slightly more potent for eliciting {beta}-arrestin-2
binding compared with cysLTs. Furthermore, LTE4 is nearly inactive
in this assay compared with its weak partial agonist activity in
the aequorin system. In a vascular leakage assay, NMLTC4 is potent
and active in mice overexpressing hCysLT2 receptor in endothelium,
whereas the response is abrogated in CysLT2 receptor knockout mice.
Therefore, NMLTC4 is a potent subtype selective agonist for the CysLT2
receptor in vitro and in vivo, and it will be useful to elucidate
its biological roles.},
comment = {10.1124/mol.110.069054},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/79/2/270}
}
@ARTICLE{Yan2011a,
author = {Yan, Han and Mitschelen, Matthew and Bixler, Georgina V and Brucklacher,
Robert M and Farley, Julie A and Han, Song and Freeman, Willard M
and Sonntag, William E},
title = {Circulating IGF1 regulates hippocampal IGF1 levels and brain gene
expression during adolescence},
journal = {J. Endocrinol.},
year = {2011},
volume = {211},
pages = {27-37},
number = {1},
abstract = {GH and its anabolic mediator, IGF1, are important not only in somatic
growth but also in the regulation of brain function. Even though
GH treatment has been used clinically to improve body composition
and exercise capacity in adults, its influence on central nervous
system function has only recently been recognized. This is also the
case for children with childhood-onset GH deficiency (GHD) where
GH has been used to stimulate bone growth and enhance final adult
height. Circulating IGF1 is transported across the blood-brain barrier
and IGF1 and its receptors are also synthesized in the brain by neurons
and glial and endothelial cells. Nevertheless, the relationship between
circulating IGF1 and brain IGF1 remains unclear. This study, using
a GH-deficient dwarf rat model and peripheral GH replacement, investigated
the effects of circulating IGF1 during adolescence on IGF1 levels
in the brain. Our results demonstrated that hippocampal IGF1 protein
concentrations during adolescence are highly regulated by circulating
IGF1, which were reduced by GHD and restored by systematic GH replacement.
Importantly, IGF1 levels in the cerebrospinal fluid were decreased
by GHD but not restored by GH replacement. Furthermore, analysis
of gene expression using microarrays and RT-PCR indicated that circulating
IGF1 levels did not modify the transcription of Igf1 or its receptor
in the hippocampus but did regulate genes that are involved in microvascular
structure and function, brain development, and synaptic plasticity,
which potentially support brain structures involved in cognitive
function during this important developmental period.},
doi = {10.1530/JOE-11-0200},
eprint = {http://joe.endocrinology-journals.org/cgi/reprint/211/1/27.pdf},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/211/1/27}
}
@ARTICLE{Yan2007,
author = {Yan, Q. and Zhang, Y. and Li, W. and DenBesten, P.K.},
title = {Micromolar Fluoride Alters Ameloblast Lineage Cells in vitro},
journal = {Journal of Dental Research},
year = {2007},
volume = {86},
pages = {336--340},
number = {4},
month = apr,
abstract = {Fluorosed enamel is caused by exposure to fluoride during tooth formation.
The objective of this study was to determine whether epithelial ameloblast-lineage
cells, derived from the human enamel organ, are directly affected
by micromolar concentrations of fluoride. Cells were cultured in
the presence of fluoride, and proliferation was measured by BrdU
incorporation. The effect of 0, 10, or 20 {micro}M fluoride on apoptosis
was determined by the flow cytometry apoptotic index. The effects
of fluoride on gene expression were investigated by SuperArray microarray
analysis and real-time PCR. Fluoride had a biphasic effect on cell
proliferation, with enhanced proliferation at 16 {micro}M, and reduced
proliferation at greater than 1 mM F. Flow cytometry showed that
both 10 {micro}M and 20 {micro}M NaF significantly increased the
apoptotic index of ameloblast-lineage cells. There was no general
effect of fluoride on gene expression. These results indicate multiple
effects of micromolar fluoride on ameloblast-lineage cells.},
url = {http://jdr.sagepub.com/cgi/content/abstract/86/4/336}
}
@ARTICLE{Yan2008,
author = {Yan, S. Steve and Schreckenberger, Paul C. and Zheng, Xiaotian and
Nelson, Nancy A. and Harrington, Susan M. and Tjhio, Joyce and Fedorko,
Daniel P.},
title = {An intrinsic pattern of reduced susceptibility to fluoroquinolones
in pediatric isolates of Streptococcus pyogenes},
journal = {Diagnostic Microbiology and Infectious Disease},
year = {2008},
volume = {62},
pages = {205--209},
number = {2},
month = oct,
abstract = {A total of 116 clinical isolates collected in 2003 from a tertiary
pediatric hospital and a primary pediatric department in Chicago,
IL, were screened for reduced susceptibility to selected fluoroquinolones
by disc diffusion. Correlation between reduced susceptibility and
point mutations in the quinolone resistance-determining region of
parC and gyrA genes was evaluated, and point mutations were compared
with other reports of isolates derived from adult or mixed patient
populations. Nine percent of isolates had reduced susceptibility
to 1 or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin,
and moxifloxacin. A single point mutation (Ser-79) in parC seemed
responsible for the reduced susceptibility. Resistant Streptococcus
pyogenes isolates were compared using M/emm type, repetitive sequence-based
PCR (rep-PCR), and pulsed-field gel electrophoresis (PFGE). Rep-PCR
provided no more separation of strains than M/emm typing, and PFGE
results with SgrAI were more discriminatory than with SmaI. The majority
of these isolates were M/emm type 6. PFGE analysis using SgrAI demonstrated
2 different resistant strains among the M/emm type 6 isolates. The
findings suggest that a population of S. pyogenes with an intrinsic
reduced susceptibility to fluoroquinolones exists in pediatric clinical
isolates. Monitoring of amino acid changes in both parC and gyrA
will assist in the prediction of emergence of high-level fluoroquinolone
resistance.},
issn = {0732-8893},
keywords = {Streptococcus pyogenes, Pediatric isolates, M/emm type, Fluoroquinolones,
Resistance, Point mutation},
url = {http://www.sciencedirect.com/science/article/B6T60-4SRDF8J-1/2/066d5412ab78aae3c078468cdd4337a5}
}
@ARTICLE{Yan2010,
author = {Yan, Zhong-Qiang and Shen, Ding-Xia and Cao, Jing-Rong and Chen,
Rong and Wei, Xing and Liu, Li-Ping and Xu, Xiu-Li},
title = {Susceptibility patterns and molecular epidemiology of multidrug-resistant
Acinetobacter baumannii strains from three military hospitals in
China},
journal = {International Journal of Antimicrobial Agents},
year = {2010},
volume = {35},
pages = {269--273},
number = {3},
month = mar,
abstract = {To date, little has been reported on the susceptibility patterns and
molecular characterisation of multidrug-resistant Acinetobacter baumannii
(MDRAB) clinical isolates from different Chinese military hospitals.
In this study, 49 MDRAB strains were collected from three military
hospitals during 2007. The minimum inhibitory concentrations (MICs)
of 13 antibiotics were determined for each strain. Genotyping and
dendrogram analysis of MDRAB strains were performed using the repetitive
sequence-based polymerase chain reaction (rep-PCR) DiversiLab(TM)
Microbial Typing System. PCR screening was carried out to investigate
the distribution of various genes contributing to each resistance
phenotype in the main clonal types. The rates of resistance to the
majority of antibiotics tested varied between 75.5% and 100%, with
the exception of polymyxin B. Two DiversiLab rep-PCR clones (A and
B) were widespread in three hospitals in different cities, one clone
(D) existed only in two hospitals located in the same city (Beijing),
and the other two clones (C and E) were present in only one hospital.
In addition, this study shows a high distribution of intI1, ISAba1,
blaOXA-23, blaADC, adeB, adeJ, abeM and tet(B) genes, which mediate
resistance to structurally unrelated antimicrobials in MDRAB isolates.
These results suggest that all isolates were resistant to at least
three classes of antibiotics. In addition, clonal dissemination among
the three hospitals located in two different cities in China, previously
documented in many regions of Europe and Asia-Pacific nations, emphasises
the epidemic potential of these MDRAB isolates.},
issn = {0924-8579},
keywords = {Multidrug-resistant Acinetobacter baumannii, DiversiLab(TM) Microbial
Typing System, Clone, Susceptibility testing},
url = {http://www.sciencedirect.com/science/article/pii/S0924857909005020}
}
@ARTICLE{Yanagi2010,
author = {Yanagi, Teruki and Akiyama, Masashi and Nishihara, Hiroshi and Ishikawa,
Junko and Sakai, Kaori and Miyamura, Yuki and Naoe, Ayano and Kitahara,
Takashi and Tanaka, Shinya and Shimizu, Hiroshi},
title = {Self-Improvement of Keratinocyte Differentiation Defects During Skin
Maturation in ABCA12-Deficient Harlequin Ichthyosis Model Mice},
journal = {Am. J. Pathol.},
year = {2010},
volume = {177},
pages = {106--118},
number = {1},
month = jul,
abstract = {Harlequin ichthyosis (HI) is caused by loss-of-function mutations
in the keratinocyte lipid transporter ABCA12. The patients often
die in the first 1 or 2 weeks of life, although HI survivors' phenotypes
improve within several weeks after birth. In order to clarify the
mechanisms of phenotypic recovery, we studied grafted skin and keratinocytes
from Abca12-disrupted (Abca12-/-) mice showing abnormal lipid transport.
Abca12-/- neonatal epidermis showed significantly reduced total ceramide
amounts and aberrant ceramide composition. Immunofluorescence and
immunoblotting of Abca12-/- neonatal epidermis revealed defective
profilaggrin/filaggrin conversion and reduced protein expression
of the differentiation-specific molecules, loricrin, kallikrein 5,
and transglutaminase 1, although their mRNA expression was up-regulated.
In contrast, Abca12-/- skin grafts kept in a dry environment exhibited
dramatic improvements in all these abnormalities. Increased transepidermal
water loss, a parameter representing barrier defect, was remarkably
decreased in grafted Abca12-/- skin. Ten-passage sub-cultured Abca12-/-
keratinocytes showed restoration of intact ceramide distribution,
differentiation-specific protein expression and profilaggrin/filaggrin
conversion, which were defective in primary-cultures. Using cDNA
microarray analysis, lipid transporters including four ATP-binding
cassette transporters were up-regulated after sub-culture of Abca12-/-
keratinocytes compared with primary-culture. These results indicate
that disrupted keratinocyte differentiation during the fetal development
is involved in the pathomechanism of HI and, during maturation, Abca12-/-
epidermal keratinocytes regain normal differentiation processes.
This restoration may account for the skin phenotype improvement observed
in HI survivors.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/177/1/106}
}
@ARTICLE{Yanagida2011,
author = {Atsuko Yanagida and Keiko Iwaisako and Etsuro Hatano and Kojiro Taura
and Fumiaki Sato and Masato Narita and Hiromitsu Nagata and Hiroyuki
Asechi and Shinji Uemoto and Makoto Kinoshita},
title = {Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4
and myofibroblastic transformation of hepatic stellate cells},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},
year = {2011},
volume = {1812},
pages = {1403 - 1411},
number = {11},
abstract = {Background/Aims Sept4, a subunit of the septin cytoskeleton specifically
expressed in quiescent hepatic stellate cells (HSCs), is downregulated
through transdifferentiation to fibrogenic and contractile myofibroblastic
cells. Since Sept4−/−mice are prone to liver fibrosis, we aimed
to identify the unknown molecular network underlying liver fibrosis
by probing the association between loss of Sept4 and accelerated
transdifferentiation of HSCs. Methods We compared the transcriptomes
of Sept4+/+ and Sept4−/− HSCs undergoing transdifferentiation
by DNA microarray and quantitative reverse transcription polymerase
chain reaction (RT-PCR) analysis. Because Dickkopf2 (Dkk2) gene expression
is reduced in Sept4−/− HSCs, we tested whether supplementing
Dkk2 could suppress myofibroblastic transformation of Sept4−/−
HSCs. We tested the involvement of the canonical Wnt pathway in this
process by using a lymphoid enhancer-binding factor/transcription
factor-luciferase reporter assay. Results We observed consistent
upregulation of Dkk2 in primary cultured HSCs and in a carbon tetrachloride
liver fibrosis in mice, which was decreased in the absence of Sept4.
Supplementation with Dkk2 suppressed the induction of pro-fibrotic
genes (α-smooth muscle actin and 2 collagen genes) and induced an
anti-fibrotic gene (Smad7) in Sept4−/− HSCs. In human liver specimens
with inflammation and fibrosis, Dkk2 immunoreactivity appeared to
be positively correlated with the degree of fibrotic changes. Conclusions
Pro-fibrotic transformation of HSCs through the loss of Sept4 is,
in part, due to reduced expression of Dkk2 and its homologues, and
the resulting disinhibition of the canonical Wnt pathway.},
doi = {10.1016/j.bbadis.2011.06.015},
issn = {0925-4439},
keywords = {Septin},
url = {http://www.sciencedirect.com/science/article/pii/S0925443911001414}
}
@ARTICLE{Yanagisawa2010,
author = {Yanagisawa, Kiyoshi and Konishi, Hiroyuki and Arima, Chinatsu and
Tomida, Shuta and Takeuchi, Toshiyuki and Shimada, Yukako and Yatabe,
Yasushi and Mitsudomi, Tetsuya and Osada, Hirotaka and Takahashi,
Takashi},
title = {Novel Metastasis-Related Gene CIM Functions in the Regulation of
Multiple Cellular Stress-Response Pathways},
journal = {Cancer Res.},
year = {2010},
volume = {70},
pages = {9949--9958},
number = {23},
month = dec,
abstract = {Various stresses of the tumor microenvironment produced by insufficient
nutrients, pH, and oxygen can contribute to the generation of altered
metabolic and proliferative states that promote the survival of metastatic
cells. Among many cellular stress-response pathways activated under
such conditions are the hypoxia-inducible factor (HIF) pathway and
the unfolded protein response (UPR), which is elicited as a response
to endoplasmic reticulum (ER) stress. In this study, we report the
identification of a novel cancer invasion and metastasis-related
gene (hereafter referred to as CIM, also called ERLEC1), which influences
both of these stress-response pathways to promote metastasis. CIM
was identified by comparing the gene expression profile of a highly
metastatic human lung cancer cell line with its weakly metastatic
parental clone. We showed that CIM is critical for metastatic properties
in this system. Proteomic approaches combined with bioinformatic
analyses revealed that CIM has multifaceted roles in controlling
the response to hypoxia and ER stress. Specifically, CIM sequestered
OS-9 from the HIF-1{alpha} complex and PHD2, permitting HIF-1{alpha}
accumulation by preventing its degradation. Ectopic expression of
CIM in lung cancer cells increased their tolerance to hypoxia. CIM
also modulated UPR through interaction with the key ER stress protein
BiP, influencing cell proliferation under ER stress conditions. Our
findings shed light on how tolerance to multiple cellular stresses
at a metastatic site can be evoked by an integrated mechanism involving
CIM, which can function to coordinate those responses in a manner
that promotes metastatic cell survival. Cancer Res; 70(23); 9949-58.
(C)2010 AACR.},
comment = {10.1158/0008-5472.CAN-10-1055},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/70/23/9949}
}
@ARTICLE{Yang2004,
author = {Yang, Allen S. and Estecio, Marcos R. H. and Doshi, Ketan and Kondo,
Yutaka and Tajara, Eloiza H. and Issa, Jean-Pierre J.},
title = {A simple method for estimating global DNA methylation using bisulfite
PCR of repetitive DNA elements},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {e38--},
number = {3},
month = feb,
abstract = {We report a method for studying global DNA methylation based on using
bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive
elements, such as Alu elements and long interspersed nucleotide elements
(LINE). The PCR product, which represents a pool of approximately
15 000 genomic loci, could be used for direct sequencing, selective
restriction digestion or pyrosequencing, in order to quantitate DNA
methylation. By restriction digestion or pyrosequencing, the assay
was reproducible with a standard deviation of only 2% between assays.
Using this method we found that almost two-thirds of the CpG methylation
sites in Alu elements are mutated, but of the remaining methylation
target sites, 87% were methylated. Due to the heavy methylation of
repetitive elements, this assay was especially useful in detecting
decreases in DNA methylation, and this assay was validated by examining
cell lines treated with the methylation inhibitor 5-aza-2'deoxycytidine
(DAC), where we found a 1-16% decrease in Alu element and 18-60%
LINE methylation within 3 days of treatment. This method can be used
as a surrogate marker of genome-wide methylation changes. In addition,
it is less labor intensive and requires less DNA than previous methods
of assessing global DNA methylation.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/3/e38}
}
@ARTICLE{Yang2009,
author = {Yang, Chen and Huang, Cheng-Hung and Cheong, Mei-Leng and Hung, Kun-Long
and Lin, Lung-Huang and Yu, Yeong-Seng and Chien, Chih-Cheng and
Huang, Huei-Chen and Chen, Chan-Wei and Huang, Chi-Jung},
title = {Unambiguous molecular detections with multiple genetic approach for
the complicated chromosome 22q11 deletion syndrome},
journal = {BMC Medical Genetics},
year = {2009},
volume = {10},
pages = {16},
number = {1},
abstract = {BACKGROUND:Chromosome 22q11 deletion syndrome (22q11DS) causes a developmental
disorder during the embryonic stage, usually because of hemizygous
deletions. The clinical pictures of patients with 22q11DS vary because
of polymorphisms: on average, approximately 93% of affected individuals
have a de novo deletion of 22q11, and the rest have inherited the
same deletion from a parent. Methods using multiple genetic markers
are thus important for the accurate detection of these microdeletions.METHODS:We
studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy
controls from unrelated Taiwanese families. We determined genomic
variance using microarray-based comparative genomic hybridization
(array-CGH), quantitative real-time polymerase chain reaction (qPCR)
and multiplex ligation-dependent probe amplification (MLPA).RESULTS:Changes
in genomic copy number were significantly associated with clinical
manifestations for the classical criteria of 22q11DS using MPLA and
qPCR (p < 0.01). An identical deletion was shown in three affected
infants by MLPA. These reduced DNA dosages were also obtained partially
using array-CGH and confirmed by qPCR but with some differences in
deletion size.CONCLUSION:Both MLPA and qPCR could produce a clearly
defined range of deleted genomic DNA, whereas there must be a deleted
genome that is not distinguishable using MLPA. These data demonstrate
that such multiple genetic approaches are necessary for the unambiguous
molecular detection of these types of complicated genomic syndromes.},
doi = {10.1186/1471-2350-10-16},
issn = {1471-2350},
pubmedid = {19243607},
url = {http://www.biomedcentral.com/1471-2350/10/16}
}
@ARTICLE{Yang2011d,
author = {Yang, Dong and Xiong, Yuanyan and Kim, Hyeung and He, Quanyuan and
Li, Yumei and Chen, Rui and Songyang, Zhou},
title = {Human telomeric proteins occupy selective interstitial sites},
journal = {Cell Res},
year = {2011},
pages = {--},
month = mar,
issn = {1748-7838},
publisher = {Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences},
url = {http://dx.doi.org/10.1038/cr.2011.39}
}
@ARTICLE{Yang2010e,
author = {Yang, Dong-Yan and Wang, Xue-Lin and Deng, Ping-Jian and Zhou, Xiang-Yang
and Wu, Xiao-Jin and Wu, Shui-Qing and Yang, Xiao-Ke and Hou, Hong-Li
and Yang, Yong-Cun and Zhang, Hai-Long and Liu, Jin},
title = {An approach to evaluate the reliability of hybridization-based and
sequencing-based gene expression profiling technologies},
journal = {Biotechnol Progress},
year = {2010},
volume = {26},
pages = {1230--1239},
number = {5},
abstract = {Abstract Hybridization-based and sequencing-based technologies have
found a widespread application in gene expression profiling analysis
but much ambiguity exists regarding their reliability. This study
developed a framework based on three parameters: detection ability,
repeatability, and accuracy to evaluate the reliability of gene expression
profiling technologies. The fraction of coverage of detected transcript
category, the degree of variance for the number of differentially
expressed genes (DEGs), the consistency of DEG category, and suspected
false discovery rate (sFDR) were first introduced as statistical
indices. In order to validate the availability of these indices,
based on the same RNA extract, the analysis was performed by comparing
gene expression differences between wild-type and transgenic rice
using deep sequencing and microarray. The results suggested that
the parameters were available and showed advances in the determination
of gene expression differences. Based on relative self-comparison
design, suspected false positive genes were easily identified from
all DEGs detected, which was difficult for quantitative real-time
polymerase chain reaction (qRT-PCR) validation when the count of
DEGs was enormous. In addition, sFDRs had advantages in the accuracy
evaluation for previous datasets. © 2010 American Institute of Chemical
Engineers Biotechnol. Prog., 2010},
issn = {1520-6033},
keywords = {hybridization-based, sequencing-based, gene expression profiling,
reliability, evaluation},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/btpr.459}
}
@ARTICLE{Yang2009a,
author = {Yang, Guang and Thieu, Khanh and Tsai, Kenneth Y. and Piris, Adriano
and Udayakumar, Durga and Njauw, Ching-Ni Jenny and Ramoni, Marco
F. and Tsao, Hensin},
title = {Dynamic Gene Expression Analysis Links Melanocyte Growth Arrest with
Nevogenesis},
journal = {Cancer Res.},
year = {2009},
volume = {69},
pages = {9029--9037},
number = {23},
month = dec,
abstract = {Like all primary cells in vitro, normal human melanocytes exhibit
a physiologic decay in proliferative potential as it transitions
to a growth-arrested state. The underlying transcriptional program(s)
that regulate this phenotypic change is largely unknown. To identify
molecular determinants of this process, we performed a Bayesian-based
dynamic gene expression analysis on primary melanocytes undergoing
proliferative arrest. This analysis revealed several related clusters
whose expression behavior correlated with the melanocyte growth kinetics;
we designated these clusters the melanocyte growth arrest program
(MGAP). These MGAP genes were preferentially represented in benign
melanocytic nevi over melanomas and selectively mapped to the hepatocyte
fibrosis pathway. This transcriptional relationship between melanocyte
growth stasis, nevus biology, and fibrogenic signaling was further
validated in vivo by the demonstration of strong pericellular collagen
deposition within benign nevi but not melanomas. Taken together,
our study provides a novel view of fibroplasia in both melanocyte
biology and nevogenesis. [Cancer Res 2009;69(23):9029-37]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/69/23/9029}
}
@ARTICLE{Yang2010c,
author = {Yang, Haiyuan and Hu, Liwei and Hurek, Thomas and Reinhold-Hurek,
Barbara},
title = {Global characterization of the root transcriptome of a wild species
of rice, Oryza longistaminata, by deep sequencing},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {705},
number = {1},
abstract = {BACKGROUND:Oryza longistaminata, an AA genome type (2 n = 24), originates
from Africa and is closely related to Asian cultivated rice (O. sativa
L.). It contains various valuable traits with respect to tolerance
to biotic and abiotic stress, QTLs with agronomically important traits
and high ability to use nitrogen efficiently (NUE). However, only
limited genomic or transcriptomic data of O. longistaminata are currently
available.RESULTS:In this study we present the first comprehensive
characterization of the O. longistaminata root transcriptome using
454 pyrosequencing. One sequencing run using a normalized cDNA library
from O. longistaminata roots adapted to low N conditions generated
337,830 reads, which assembled into 41,189 contigs and 30,178 singletons.
By similarity search against protein databases, putative functions
were assigned to over 34,510 uni-ESTs. Comparison with ESTs derived
from cultivated rice collections revealed expressed genes across
different plant species, however 16.7% of the O. longistaminata ESTs
had not been detected as expressed in O. sativa. Additionally, 15.7%
had no significant similarity to known sequences. RT-PCR and Southern
blot analyses confirmed the expression of selected novel transcripts
in O. longistaminata.CONCLUSION:Our results show that one run using
a Genome Sequencer FLX from 454 Life Science/Roche generates sufficient
genomic information for adequate de novo assembly of a large number
of transcripts in a wild rice species, O. longistaminata. The generated
sequence data are publicly available and will facilitate gene discovery
in O. longistaminata and rice functional genomic studies. The large
number of abundant of novel ESTs suggests different metabolic activity
in O. longistaminata roots in comparison to O. sativa roots.},
doi = {10.1186/1471-2164-11-705},
issn = {1471-2164},
pubmedid = {21159186},
url = {http://www.biomedcentral.com/1471-2164/11/705}
}
@ARTICLE{Yang2011e,
author = {Ines Yang and Sára Beszteri and Urban Tillmann and Allan Cembella
and Uwe John},
title = {Growth- and nutrient-dependent gene expression in the toxigenic marine
dinoflagellate Alexandrium minutum},
journal = {Harmful Algae},
year = {2011},
volume = {12},
pages = {55 - 69},
number = {0},
abstract = {The toxigenic marine dinoflagellate Alexandrium minutum forms toxic
blooms causing paralytic shellfish poisoning (PSP), primarily in
coastal waters, throughout the world. We examined effects on physiology
and gene expression patterns associated with growth and nutrient
starvation in a toxic strain of A. minutum. Bloom-relevant factors,
including growth rate, intracellular toxin content, allelochemical
activity and nutrient status were investigated in A. minutum cultures
grown under different environmental regimes. Allelochemical activity
of A. minutum cultures, quantified with a cryptomonad Rhodomonas
bioassay, increased with age but was independent of nutrient status.
The phenotypic data were integrated and compared with gene expression
in cell samples taken at selected points along the growth curve.
We observed 489 genes consistently differentially expressed between
exponentially growing and growth-limited cultures. The expression
pattern of stationary-phase cultures was characterized by conspicuous
down-regulation of translation-associated genes, up-regulation of
sequences involved in intracellular signalling and some indications
of increased activity of selfish genetic elements such as transposons.
Treatment-specific patterns included five genes regulated in parallel
in all nutrient-limited cultures. The conspicuous decrease in photosynthetic
performance identified in N-starved cultures was paralleled by down-regulation
of chloroplast-associated genes.
The particular gene expression patterns we identified as specifically
linked with exponential growth, cessation of growth or nutrient limitation
may be suitable biomarkers for indicating the beginning of growth
limitation in field- or mesocosm studies.},
doi = {10.1016/j.hal.2011.08.012},
issn = {1568-9883},
keywords = {Alexandrium minutum},
url = {http://www.sciencedirect.com/science/article/pii/S1568988311000977}
}
@ARTICLE{Yang2010d,
author = {Yang, Ines and John, Uwe and Beszteri, Sára and Glöckner, Gernot
and Krock, Bernd and Goesmann, Alexander and Cembella, Allan},
title = {Comparative gene expression in toxic versus non-toxic strains of
the marine dinoflagellate Alexandrium minutum },
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {248},
number = {1},
abstract = {BACKGROUND:The dinoflagellate Alexandrium minutum typically produces
paralytic shellfish poisoning (PSP) toxins, which are known only
from cyanobacteria and dinoflagellates. While a PSP toxin gene cluster
has recently been characterized in cyanobacteria, the genetic background
of PSP toxin production in dinoflagellates remains elusive.RESULTS:We
constructed and analysed an expressed sequence tag (EST) library
of A. minutum, which contained 15,703 read sequences yielding a total
of 4,320 unique expressed clusters. Of these clusters, 72% combined
the forward-and reverse reads of at least one bacterial clone. This
sequence resource was then used to construct an oligonucleotide microarray.
We analysed the expression of all clusters in three different strains.
While the cyanobacterial PSP toxin genes were not found among the
A. minutum sequences, 192 genes were differentially expressed between
toxic and non-toxic strains.CONCLUSIONS:Based on this study and on
the lack of identified PSP synthesis genes in the two existent Alexandrium
tamarense EST libraries, we propose that the PSP toxin genes in dinoflagellates
might be more different from their cyanobacterial counterparts than
would be expected in the case of a recent gene transfer. As a starting
point to identify possible PSP toxin-associated genes in dinoflagellates
without relying on a priori sequence information, the sequences only
present in mRNA pools of the toxic strain can be seen as putative
candidates involved in toxin synthesis and regulation, or acclimation
to intracellular PSP toxins.},
doi = {10.1186/1471-2164-11-248},
issn = {1471-2164},
pubmedid = {20403159},
url = {http://www.biomedcentral.com/1471-2164/11/248}
}
@ARTICLE{Yang2006,
author = {Yang, Ivana V.},
title = {Use of External Controls in Microarray Experiments},
journal = {Methods Enzymol},
year = {2006},
volume = {Volume 411},
pages = {50--63},
abstract = {DNA microarray analysis has become the most widely used technique
for the study of gene expression patterns on a genomic scale. Microarray
analysis is a complex technique involving many steps, and a number
of commercial and in[hyphen (true graphic)]house developed arrays
and protocols for data collection and analysis are used in different
laboratories. Inclusion of external or spike[hyphen (true graphic)]in
RNA controls allows one to evaluate the variability in gene expression
measurements and to facilitate the comparison of data collected using
different platforms and protocols. This chapter describes what external
controls are, which collections of spike[hyphen (true graphic)]in
controls are available to researchers, and how they are implemented
in the laboratory. Applications of external controls in the assessment
of microarray performance, normalization strategies, the evaluation
of algorithms for gene expression analysis, and the potential to
quantify absolute mRNA levels are discussed.},
booktitle = {DNA Microarrays, Part B: Databases and Statistics},
editor = {Kimmel, Alan and Oliver, Brian},
issn = {0076-6879},
publisher = {Academic Press},
url = {http://www.sciencedirect.com/science/article/B7CV2-4KS5C9T-4/2/cbf7aba61e1ffce1102fe7562c12d79c}
}
@ARTICLE{Yang2011b,
author = {Yang, Jianxin and MacDougall, Margit and McDowell, Michael and Xi,
Li and Wei, Ru and Zavadoski, William and Molloy, Mark and Baker,
John and Kuhn, Max and Cabrera, Over and Treadway, Judith},
title = {Polyomic profiling reveals significant hepatic metabolic alterations
in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon
therapies for diabetes},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {281},
number = {1},
abstract = {BACKGROUND:Glucagon is an important hormone in the regulation of glucose
homeostasis, particularly in the maintenance of euglycemia and prevention
of hypoglycemia. In type 2 Diabetes Mellitus (T2DM), glucagon levels
are elevated in both the fasted and postprandial states, which contributes
to inappropriate hyperglycemia through excessive hepatic glucose
production. Efforts to discover and evaluate glucagon receptor antagonists
for the treatment of T2DM have been ongoing for approximately two
decades, with the challenge being to identify an agent with appropriate
pharmaceutical properties and efficacy relative to potential side
effects. We sought to determine the hepatic & systemic consequence
of full glucagon receptor antagonism through the study of the glucagon
receptor knock-out mouse (Gcgr-/-) compared to wild-type littermates.RESULTS:Liver
transcriptomics was performed using Affymetric expression array profiling,
and liver proteomics was performed by iTRAQ global protein analysis.
To complement the transcriptomic and proteomic analyses, we also
conducted metabolite profiling (~200 analytes) using mass spectrometry
in plasma. Overall, there was excellent concordance (R = 0.88) for
changes associated with receptor knock-out between the transcript
and protein analysis. Pathway analysis tools were used to map the
metabolic processes in liver altered by glucagon receptor ablation,
the most notable being significant down-regulation of gluconeogenesis,
amino acid catabolism, and fatty acid oxidation processes, with significant
up-regulation of glycolysis, fatty acid synthesis, and cholesterol
biosynthetic processes. These changes at the level of the liver were
manifested through an altered plasma metabolite profile in the receptor
knock-out mice, e.g. decreased glucose and glucose-derived metabolites,
and increased amino acids, cholesterol, and bile acid levels.CONCLUSIONS:In
sum, the results of this study suggest that the complete ablation
of hepatic glucagon receptor function results in major metabolic
alterations in the liver, which, while promoting improved glycemic
control, may be associated with adverse lipid changes.},
doi = {10.1186/1471-2164-12-281},
issn = {1471-2164},
pubmedid = {21631939},
url = {http://www.biomedcentral.com/1471-2164/12/281}
}
@ARTICLE{Yang2007,
author = {Yang, Jeannie H. and Amoui, Mehran and Lau, K.-H. William},
title = {Targeted deletion of the osteoclast protein-tyrosine phosphatase
(PTP-oc) promoter prevents RANKL-mediated osteoclastic differentiation
of RAW264.7 cells},
journal = {FEBS Letters},
year = {2007},
volume = {581},
pages = {2503--2508},
number = {13},
month = may,
abstract = {An osteoclastic protein-tyrosine phosphatase, PTP-oc, shares the same
gene with a renal PTP, Glepp1. This study demonstrated that targeted
deletion of PTP-oc promoter by homologous recombination in RAW264.7
cells completely abolished PTP-oc expression without affecting Glepp1
expression. This strategy to inhibit PTP-oc function has three advantages
over commonly used gene knock down strategies (e.g., small interference
RNA). This strategy: (1) yielded cells completely devoid of PTP-oc,
(2) had no off-target gene silencing effects, and (3) did not affect
Glepp1 expression. The inability of PTP-oc-deficient RAW264.7 cells
to undergo RANKL-mediated osteoclastic differentiation confirmed
a regulatory role for PTP-oc in RANKL-mediated osteoclast differentiation.},
issn = {0014-5793},
keywords = {Osteoclasts, Protein-tyrosine phosphatase, Promoter, Homologous recombination,
Promoter deletion},
url = {http://www.sciencedirect.com/science/article/B6T36-4NN1PY7-1/2/e5a1190cdcd01ac6292145212d1dca47}
}
@ARTICLE{Yang2009b,
author = {Yang, Jeong-Yeh and Della-Fera, Mary Anne and Rayalam, Srujana and
Park, Hea Jin and Ambati, Suresh and Hausman, Dorothy B. and Hartzell,
Diane L. and Baile, Clifton A.},
title = {Regulation of adipogenesis by medium-chain fatty acids in the absence
of hormonal cocktail},
journal = {The Journal of Nutritional Biochemistry},
year = {2009},
volume = {20},
pages = {537--543},
number = {7},
month = jul,
abstract = {We report here that octanoate and decanoate, 8-carbon and 10-carbon
medium-chain fatty acids (MCFA), decreased adipogenesis in 3T3-L1
preadipocytes when treated with standard hormonal cocktail, but increased
adipogenesis in a dose-dependent manner (with decanoate being more
effective) when treated with basal media. Addition of dexamethasone
to basal medium with either octanoate or decanoate further increased
adipogenesis. In order to understand the adipogenic effects of MCFA
in the absence of standard hormonal cocktail, postconfluent 3T3-L1
preadipocytes were treated with octanoate or decanoate, and the change
in the expression of several adipogenic transcription factors and
enzymes was investigated using real-time RT-PCR. Octanoate and decanoate
up-regulated the mRNA expression of peroxisome-proliferator-activated
receptor (PPAR) [gamma], CCAAT/enhancer-binding protein (C/EBP) [alpha],
fatty-acid-binding protein, sterol-regulatory element binding protein
1c, lipoprotein lipase and hormone-sensitive lipase, and the protein
expression of PPAR[gamma] and C/EBP[alpha], with decanoate being
more effective. Moreover, the PPAR[gamma] antagonist GW9662 inhibited
MCFA-induced lipid accumulation by about 50%. Decanoate and octanoate,
to a lesser degree, increased lipid accumulation, which was associated
with an increase in glycerol-3-phosphate dehydrogenase activity.
These results show that octanoate and decanoate may stimulate differentiation
of preadipocytes, at least in part, by their influence on the expression
of PPAR[gamma] and other adipocyte-specific factors.},
issn = {0955-2863},
keywords = {MCFA, Adipocytes, Preadipocytes, Adipocyte-Specific Genes, GPDH activity},
url = {http://www.sciencedirect.com/science/article/B6T8P-4TDYNVG-8/2/849dbe7eff6dede08882f55673699037}
}
@ARTICLE{Yang2011g,
author = {Yang, L and Wu, X and Wang, Y and Zhang, K and Wu, J and Yuan, Y-C
and Deng, X and Chen, L and Kim, C C H and Lau, S and Somlo, G and
Yen, Y},
title = {FZD7 has a critical role in cell proliferation in triple negative
breast cancer},
journal = {Oncogene},
year = {2011},
pages = {--},
month = may,
issn = {1476-5594},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/onc.2011.145}
}
@ARTICLE{Yang2009c,
author = {Yang, Meixiang and Ma, Chunhong and Liu, Shuxun and Sun, Jintang
and Shao, Qianqian and Gao, Wenjuan and Zhang, Yan and Li, Zewu and
Xie, Qi and Dong, Zhaogang and Qu, Xun},
title = {Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype
and promotes tumour cell migration by dendritic cell-derived osteopontin},
journal = {Immunology},
year = {2009},
volume = {128},
pages = {e237--e249},
number = {1pt2},
abstract = {Summary It is well recognized that tissue microenvironments are involved
in regulating the development and function of dendritic cells (DC).
Oxygen supply, which varies in different tissues, has been accepted
as an important microenvironmental factor in regulating the biological
functions of several immune cells and as being involved in tumour
progression and metastasis. However, little is known about the effect
of hypoxia on the biological functions of DC and the effect of these
hypoxia-conditioned DC on tumour metastasis. In this study, we analysed
the transcriptional profiles of human monocyte-derived immature DC
(imDC) and mature DC (mDC) cultured under normoxia and hypoxia by
microarray, and found a body of potential targets regulating the
functions of DC during hypoxia. In addition, the phagocytic ability
of hypoxic imDC markedly decreased compared with that of normoxic
imDC. Importantly, hypoxic DC poorly induced the proliferation of
allogeneic T cells, but polarized allogeneic CD4+ naive T cells into
a T helper type 2 (Th2) response. Moreover, hypoxic DC secreted large
amounts of osteopontin, which were responsible for the enhanced migration
of tumour cells. Therefore, our study provides new insights into
the biological functions of DC under hypoxic conditions and one of
mechanisms underlying tumour immune escape during hypoxia.},
issn = {1365-2567},
keywords = {cancer, dendritic cells, hypoxia, T helper type 2},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2008.02954.x}
}
@ARTICLE{Yang2008,
author = {Yang, Nuo and Kaur, Sippy and Volinia, Stefano and Greshock, Joel
and Lassus, Heini and Hasegawa, Kosei and Liang, Shun and Leminen,
Arto and Deng, Shan and Smith, Lori and Johnstone, Cameron N. and
Chen, Xian-Ming and Liu, Chang-Gong and Huang, Qihong and Katsaros,
Dionyssios and Calin, George Adrian and Weber, Barbara L. and Butzow,
Ralf and Croce, Carlo M. and Coukos, George and Zhang, Lin},
title = {MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic
Target in Human Epithelial Ovarian Cancer},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {10307--10314},
number = {24},
month = dec,
abstract = {MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that
negatively regulate protein-coding gene expression in a sequence-specific
manner via translational inhibition or mRNA degradation. Our recent
studies showed that miRNAs exhibit genomic alterations at a high
frequency and their expression is remarkably deregulated in ovarian
cancer, strongly suggesting that miRNAs are involved in the initiation
and progression of this disease. In the present study, we performed
miRNA microarray to identify the miRNAs associated with chemotherapy
response in ovarian cancer and found that let-7i expression was significantly
reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This
result was further validated by stem-loop real-time reverse transcription-PCR
(n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor)
and gain-of-function (by retroviral overexpression of let-7i) studies
showed that reduced let-7i expression significantly increased the
resistance of ovarian and breast cancer cells to the chemotherapy
drug, cis-platinum. Finally, using miRNA microarray, we found that
decreased let-7i expression was significantly associated with the
shorter progression-free survival of patients with late-stage ovarian
cancer (n = 72, P = 0.042). This finding was further validated in
the same sample set by stem-loop real-time reverse transcription-PCR
(n = 62, P = 0.001) and in an independent sample set by in situ hybridization
(n = 53, P = 0.049). Taken together, our results strongly suggest
that let-7i might be used as a therapeutic target to modulate platinum-based
chemotherapy and as a biomarker to predict chemotherapy response
and survival in patients with ovarian cancer. [Cancer Res 2008;68(24):10307-14]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/24/10307}
}
@ARTICLE{Yang2011,
author = {Nan Yang and Aaron Schindeler and Michelle M. McDonald and Jane T.
Seto and Peter J. Houweling and Monkol Lek and Marshall Hogarth and
Alyson R. Morse and Joanna M. Raftery and Dominic Balasuriya and
Daniel G. MacArthur and Yemima Berman and Kate GR Quinlan and John
A. Eisman and Tuan V. Nguyen and Jacqueline R. Center and Richard
L. Prince and Scott G. Wilson and Kathy Zhu and David G. Little and
Kathryn N. North},
title = {?-Actinin-3 deficiency is associated with reduced bone mass in human
and mouse},
journal = {Bone},
year = {2011},
volume = {49},
pages = {790 - 798},
number = {4},
abstract = {Bone mineral density (BMD) is a complex trait that is the single best
predictor of the risk of osteoporotic fractures. Candidate gene and
genome-wide association studies have identified genetic variations
in approximately 30 genetic loci associated with BMD variation in
humans. α-Actinin-3 (ACTN3) is highly expressed in fast skeletal
muscle fibres. There is a common null-polymorphism R577X in human
ACTN3 that results in complete deficiency of the α-actinin-3 protein
in approximately 20% of Eurasians. Absence of α-actinin-3 does not
cause any disease phenotypes in muscle because of compensation by
α-actinin-2. However, α-actinin-3 deficiency has been shown to
be detrimental to athletic sprint/power performance. In this report
we reveal additional functions for α-actinin-3 in bone. α-Actinin-3
but not α-actinin-2 is expressed in osteoblasts. The Actn3−/−
mouse displays significantly reduced bone mass, with reduced cortical
bone volume (− 14%) and trabecular number (− 61%) seen
by microCT. Dynamic histomorphometry indicated this was due to a
reduction in bone formation. In a cohort of postmenopausal Australian
women, ACTN3 577XX genotype was associated with lower BMD in an additive
genetic model, with the R577X genotype contributing 1.1% of the variance
in BMD. Microarray analysis of cultured osteoprogenitors from Actn3−/−
mice showed alterations in expression of several genes regulating
bone mass and osteoblast/osteoclast activity, including Enpp1, Opg
and Wnt7b. Our studies suggest that ACTN3 likely contributes to the
regulation of bone mass through alterations in bone turnover. Given
the high frequency of R577X in the general population, the potential
role of ACTN3 R577X as a factor influencing variations in BMD in
elderly humans warrants further study.},
doi = {10.1016/j.bone.2011.07.009},
issn = {8756-3282},
keywords = {ACTN3},
url = {http://www.sciencedirect.com/science/article/pii/S8756328211010878}
}
@ARTICLE{Yang2004a,
author = {Yang, P. and Bamlet, W.R. and Ebbert, J.O. and Taylor, W.R. and de
Andrade, M.},
title = {Glutathione pathway genes and lung cancer risk in young and old populations},
journal = {Carcinogenesis},
year = {2004},
volume = {25},
pages = {1935--1944},
number = {10},
month = oct,
abstract = {Multiple enzymes with overlapping functions and shared substrates
in the glutathione (GSH) metabolic pathway have been associated with
host susceptibility to tobacco smoke carcinogens and in lung cancer
etiology. However, few studies have investigated the differing and
interacting roles of GSH pathway enzymes with tobacco smoke exposure
on lung cancer risk in young (<50 years of age) and old (>80 years
of age) populations. Between 1997 and 2001, 237 primary lung cancer
patients (170 young, 67 old) and 234 controls (165 young, 69 old)
were enrolled at the Mayo Clinic. Using PCR amplification of genomic
DNA, polymorphic markers for {gamma}GCS, GPX1, GSTP1 (I105V and A114V),
GSTM1 and GSTT1 were genotyped. Recursive partitioning and logistic
regression models were used to build binary classification trees
and to estimate odds ratios (OR) and 95% confidence intervals for
each splitting factor. For the young age group, cigarette smoking
had the greatest association with lung cancer (OR = 3.3). For never
smokers, the dividing factors of recursive partitioning were GSTT1
(OR = 1.7), GPX1 (OR = 0.6) and GSTM1 (OR = 4.3). For the old age
group, smoking had the greatest association with lung cancer (OR
= 3.6). For smokers, the dividing factors were GPX1 (OR = 3.3) and
GSTP1 (I105V) (OR = 4.1). Results from logistic regression analyses
supported the results from RPART models. GSH pathway genes are associated
with lung cancer development in young and old populations through
differing interactions with cigarette smoking and family history.
Carefully evaluating multiple levels of gene-environment and gene-gene
interactions is critical in assessing lung cancer risk.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/25/10/1935}
}
@ARTICLE{Yang2003,
author = {Yang, Ping and Bamlet, William and Ebbert, Jon O. and Taylor, William
R. and Okuno, Scott H. and deAndrade, Mariza},
title = {O-169 Glutathione pathway genes differentially interacting with tobacco
smoking in lung cancer risk at young and old age},
journal = {Lung Cancer},
year = {2003},
volume = {41},
pages = {S50--S51},
number = {Supplement 2},
month = aug,
booktitle = {Abstract of the 10th World Conference on Lung Cancer},
issn = {0169-5002},
url = {http://www.sciencedirect.com/science/article/B6T9C-4BD9TR1-66/2/a077b0a7ddd97550d355dc3decb9d505}
}
@ARTICLE{Yang2004b,
author = {Yang, P. and Sun, Z. and Aubry, M. C. and Kosari, F. and Bamlet,
W. and Endo, C. and Molina, J. R. and Vasmatzis, G.},
title = {Study design considerations in clinical outcome research of lung
cancer using microarray analysis},
journal = {Lung Cancer},
year = {2004},
volume = {46},
pages = {215--226},
number = {2},
month = nov,
abstract = {Background: Prognosis following a diagnosis of primary lung cancer
is very poor and varies significantly even after adjusting for known
predictors. Inherent and acquired gene alterations could cause failure
in lung cancer treatment and patient survival. To search for potential
molecular markers with significant and independent predictive value
in lung cancer survival, we applied oligo-nucleotide microarray analysis,
along with patients' phenotypic profile, in a case-control study.
The focus of this report is on the methodology used in the identification
of potential genes as prognostic factors. Methods: Selected from
304 patients at Mayo Clinic, 18 stage I squamous cell lung cancer
patients who died within 2 years (high-aggressive) or lived beyond
5 years (low-aggressive) were included in this study. Both a one-to-one
matched design (paired) and a two-group design (grouped) were utilized.
Matching variables were age, gender, tumor size and grade, smoking
status, and treatment. Two-GeneChip®-array sets from Affymetrix (HG-U133)
were used. We applied multiple analytic approaches including Dchip
(Harvard University), SAM (Stanford University), ArrayTools (US National
Cancer Institute), and MAS5 (Affymetrix); and integrated multiple
results to generate the final candidate genes for further investigation.
We evaluated the consistency across the methods and the effects of
matched versus grouped design on the results. Results: Using the
same pre-processed data under the same criteria for type I error
and fold-change in expression intensity, results are 94-100% concordant
in the list of significant genes by Dchip and by ArrayTools, and
53% concordant between the paired and the grouped analysis. If using
differently pre-processed data, the concordance rate is under 6%
even by the same analytic tool. Combining results from all analyses,
we found 23 potentially important genes that may distinguish the
high- versus low-aggressive squamous cell tumors of the lung. Conclusion:
Given the generally low consistency of results across analytic algorithms
and study design, poor agreement is expected from different investigators
reporting candidate genes for the same endpoint. A well-designed
study with a carefully planned analytic strategy is critical. We
are in the process of validating the 23 preliminary candidate genes
found from this study among independent yet comparable cases.},
issn = {0169-5002},
keywords = {Lung cancer, Survival, Microarray, Study design, NSCLC, Squamous cell
carcinoma},
url = {http://www.sciencedirect.com/science/article/B6T9C-4CHGD0P-2/2/7677c4ca010ce09e2999fd264ce28c68}
}
@ARTICLE{Yang2011h,
author = {Yang, Raymond and Hanwell, Heather and Zhang, Jing and Tsao, Rong
and Meckling, Kelly Anne},
title = {Antiproliferative Activity of Pomiferin in Normal (MCF-10A) and Transformed
(MCF-7) Breast Epithelial Cells},
journal = {Journal of Agricultural and Food Chemistry},
year = {2011},
volume = {59},
pages = {13328-13336},
number = {24},
abstract = { Pomiferin and osajin are prenylated isoflavones from Osage orange
fruit that both have potent antioxidant activity in a variety of
assays. Pomiferin, in particular, has strong activity against the
superoxide anion in a photochemiluminescence (PCL) assay system.
In vitro, pomiferin, but not osajin, demonstrated selective antiproliferative
activity against the tumorigenic breast epithelial cell line MCF-7
(IC50 = 5.2 μM) with limited toxicity toward nontumorigenic breast
epithelial cells (MCF-10A). The differential sensitivity of normal
and tumorigenic cells to the antiproliferative action of pomiferin
was examined further by using cDNA microarrays. With a stringent
cutoff of p < 0.01, a total of 94 genes were significantly differentially
expressed between MCF-7 and MCF-10A cells; 80 up-regulated and 14
down-regulated when cells were exposed to 5 μM pomiferin for 24
h. Fold changes by microarray analysis were confirmed using RT-qPCR,
and the most significant changes were found with genes related to
antioxidant enzymes. Genes involved in mitotic inhibition and apoptotic
regulations were also found to be up-regulated. Pomiferin is therefore
a good anticancer candidate agent that may be useful either alone
or in combination with other therapeutic agents and, because of its
selectivity toward tumor cells, likely to have fewer side effects
that classic chemotherapy drugs. },
doi = {10.1021/jf202898g},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/jf202898g},
url = {http://pubs.acs.org/doi/abs/10.1021/jf202898g}
}
@ARTICLE{Yang2004c,
author = {Yang, Rongcun and Murillo, Francisco Martinez and Cui, Hengmi and
Blosser, Richard and Uematsu, Satoshi and Takeda, Kiyoshi and Akira,
Shizuo and Viscidi, Raphael P. and Roden, Richard B. S.},
title = {Papillomavirus-Like Particles Stimulate Murine Bone Marrow-Derived
Dendritic Cells To Produce Alpha Interferon and Th1 Immune Responses
via MyD88},
journal = {J. Virol.},
year = {2004},
volume = {78},
pages = {11152--11160},
number = {20},
month = oct,
abstract = {Dendritic cells (DCs) link innate and adaptive immunity by sensing
pathogens or vaccinogens and signaling a variety of defense responses.
Since human papillomavirus type 16 L1 virus-like particles (HPV16
VLPs) induce a potent, protective immune response after vaccination,
we examined their recognition by DCs. HPV16 VLPs cause phenotypic
maturation of murine bone marrow-derived DCs (BMDCs), and immunization
of mice with HPV16 VLP-loaded BMDCs or HPV16 VLPs alone induced T
helper 1 (Th1)-biased immune responses. Analysis of transcriptional
responses of murine BMDCs by microarray suggested that alpha/beta
interferon (IFN-{alpha}/{beta}) transcripts and numerous proinflammatory
cytokines and chemokines are up regulated in response to HPV16 VLPs.
Indeed, the induction of IFN-{alpha}, IFN-{gamma}, and interleukin-12
(IL-12) production by BMDCs after stimulation with HPV16 VLPs was
demonstrated by quantitative enzyme-linked immunosorbent assay. Many
microbial products that induce proinflammatory responses are recognized
via Toll-like receptor (TLR) signaling through the key adaptor protein
MyD88 and activation of NF-{kappa}B, nuclear factor of activated
T cells (NF-AT), and activating protein 1 (AP-1). Reporter assays
indicated that HPV16 VLPs activated NF-{kappa}B-, NF-AT-, and AP-1-dependent
transcription in the RAW264.7 macrophage cell line. Knockdown of
MyD88 transcripts by small interfering RNA in the RAW264.7 macrophage
cell line inhibited the activation of NF-{kappa}B-, NF-AT- and AP-1-dependent
transcription by HPV16 VLP. Furthermore, MyD88-/- BMDCs failed to
up regulate IL-12 and IFN-{alpha} and -{gamma} in response to HPV16
VLPs. Finally, Th1-biased immune responses to HPV16 VLPs are dramatically
impaired in MyD88 and IFN-{alpha}/{beta} receptor-deficient mice.
This implicates TLR recognition as central to immune recognition
of HPV16 L1 VLPs.},
url = {http://jvi.asm.org/cgi/content/abstract/78/20/11152}
}
@ARTICLE{Yang2004d,
author = {Yang, Rongcun and Murillo, Francisco Martinez and Lin, Ken-Yu and
Yutzy, William H., IV and Uematsu, Satoshi and Takeda, Kiyoshi and
Akira, Shizuo and Viscidi, Raphael P. and Roden, Richard B. S.},
title = {Human Papillomavirus Type-16 Virus-Like Particles Activate Complementary
Defense Responses in Key Dendritic Cell Subpopulations},
journal = {J. Immunol.},
year = {2004},
volume = {173},
pages = {2624--2631},
number = {4},
month = aug,
abstract = {Human papillomavirus type-16 (HPV16) L1 virus-like particles (VLPs)
activate dendritic cells (DCs) and induce protective immunity. In
this study, we demonstrate, using global gene expression analysis,
that HPV16 VLPs produce quite distinct innate responses in murine
splenic DC subpopulations. While HPV16 VLPs increase transcription
of IFN-{gamma} and numerous Th1-related cytokines and chemokines
in CD8{alpha}+CD11c+ DCs, CD4+CD11c+ DCs up-regulate only type I
IFN and a different set of Th2-associated cytokines and chemokines.
Type I IFN, but not IFN-{gamma}, potentiates humoral immunity, notably
production of VLP-specific IgG2a. However, HPV16 VLP-stimulated IL-12
production by CD8{alpha}+CD11c+ DCs is augmented by autocrine IFN-{gamma}
signaling. Thus, before adaptive immunity, HPV16 VLPs signal complementary
defense responses in key DC subpopulations, indicating specialized
DC lineages with predetermined polarization.},
url = {http://www.jimmunol.org/cgi/content/abstract/173/4/2624}
}
@ARTICLE{Yang2008a,
author = {Yang, Rui-li and Li, Wu and Shi, Yong-Hui and Le, Guo-Wei},
title = {Lipoic acid prevents high-fat diet-induced dyslipidemia and oxidative
stress: A microarray analysis},
journal = {Nutrition},
year = {2008},
volume = {24},
pages = {582--588},
number = {6},
month = jun,
abstract = {Objective We previously found that lipoic acid (LA) improved high-fat
diet (HFD)-induced dyslipidemia in rats. To elucidate the molecular
mechanisms of that effect, we carried out experiments aimed at analyzing
biochemical parameters and gene expression profiles.Methods C57BL/6
mice were randomly assigned to one of three groups (n = 8). The control
group consumed an ordinary diet (4.89% fat, w/w). The other two experimental
groups were fed with an HFD (21.45% fat, w/w) or an HFD plus 0.1%
LA. After 6 wk, plasma lipid level and antioxidant status were examined.
To investigate the molecular mechanisms underlying the effects of
LA on lipid metabolism and oxidative stress, we examined gene expression
profiles in liver using the GeneChip microarray system. The differential
expression of genes of interest identified by microarray technique
was validated by real-time reverse transcription-polymerase chain
reaction.Results HFD resulted in significant alterations in lipid
profiles and a depressed antioxidant defense system. LA supplementation
induced decreases in lipid peroxidation, plasma cholesterol, triacylglycerols,
and low-density lipoprotein cholesterol and an increase in high-density
lipoprotein in HFD-fed mice. DNA microarray analysis of the liver
showed that LA ingestion upregulated the expression of genes related
to [beta]-oxidation and free radical scavenger enzymes, whereas those
involved in cholesterol synthesis were downregulated.Conclusion LA
can prevent HFD-induced dyslipidemia by modulating lipid metabolism,
especially by increasing [beta]-oxidation and decreasing cholesterol
synthesis, and oxidative stress by increasing those of free radical
scavenger enzyme gene expression.},
issn = {0899-9007},
keywords = {DNA microarray, Hyperlipidemia, Oxidative stress, Lipid metabolism,
High-fat diet},
url = {http://www.sciencedirect.com/science/article/B6TB0-4S4S5NS-2/2/290e5343b49d26861d393b7d3f26c0e9}
}
@ARTICLE{Yang2011c,
author = {Yang, Shaomin and Weng, Haibo and Chen, Lixiang and Guo, Xinhua and
Parra, Marilyn and Conboy, John and Debnath, Gargi and Lambert, Amy
J. and Peters, Luanne L. and Baines, Anthony J. and Mohandas, Narla
and An, Xiuli},
title = {Lack of Protein 4.1G Causes Altered Expression and Localization of
the Cell Adhesion Molecule Nectin-Like 4 in Testis and Can Cause
Male Infertility},
journal = {Mol. Cell. Biol.},
year = {2011},
volume = {31},
pages = {2276--2286},
number = {11},
month = jun,
abstract = {Protein 4.1G is a member of the protein 4.1 family, which in general
serves as adaptors linking transmembrane proteins to the cytoskeleton.
4.1G is thought to be widely expressed in many cells and tissues,
but its function remains largely unknown. To explore the function
of 4.1G in vivo, we generated 4.1G-/- mice and bred the mice in two
backgrounds: C57BL/6 (B6) and 129/Sv (129) hybrids (B6-129) and inbred
B6. Although the B6 4.1G-/- mice showed no obvious abnormalities,
deficiency of 4.1G in B6-129 hybrids was associated with male infertility.
Histological examinations of these 4.1G-/- mice revealed atrophy,
impaired cell-cell contact and sloughing off of spermatogenic cells
in seminiferous epithelium, and lack of mature spermatids in the
epididymis. Ultrastructural examination revealed enlarged intercellular
spaces between spermatogenic and Sertoli cells as well as the spermatid
deformities. At the molecular level, 4.1G is associated with the
nectin-like 4 (NECL4) adhesion molecule. Importantly, the expression
of NECL4 was decreased, and the localization of NECL4 was altered
in 4.1G-/- testis. Thus, our findings imply that 4.1G plays a role
in spermatogenesis by mediating cell-cell adhesion between spermatogenic
and Sertoli cells through its interaction with NECL4 on Sertoli cells.
Additionally, the finding that infertility is present in B6-129 but
not on the B6 background suggests the presence of a major modifier
gene(s) that influences 4.1G function and is associated with male
infertility.},
comment = {10.1128/MCB.01105-10},
url = {http://mcb.asm.org/cgi/content/abstract/31/11/2276}
}
@ARTICLE{Yang2011a,
author = {Yang, S. Samuel and Tu, Zheng Jin and Cheung, Foo and Xu, Wayne Wenzhong
and Lamb, JoAnn and Jung, Hans-Joachim and Vance, Carroll and Gronwald,
John},
title = {Using RNA-Seq for gene identification, polymorphism detection and
transcript profiling in two alfalfa genotypes with divergent cell
wall composition in stems},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {199},
number = {1},
abstract = {BACKGROUND:Alfalfa, [Medicago sativa (L.) sativa], a widely-grown
perennial forage has potential for development as a cellulosic ethanol
feedstock. However, the genomics of alfalfa, a non-model species,
is still in its infancy. The recent advent of RNA-Seq, a massively
parallel sequencing method for transcriptome analysis, provides an
opportunity to expand the identification of alfalfa genes and polymorphisms,
and conduct in-depth transcript profiling. RESULTS:Cell walls in
stems of alfalfa genotype 708 have higher cellulose and lower lignin
concentrations compared to cell walls in stems of genotype 773. Using
the Illumina GA-II platform, a total of 198,861,304 expression sequence
tags (ESTs, 76 bp in length) were generated from cDNA libraries derived
from elongating stem (ES) and post-elongation stem (PES) internodes
of 708 and 773. In addition, 341,984 ESTs were generated from ES
and PES internodes of genotype 773 using the GS FLX Titanium platform.
The first alfalfa (Medicago sativa) gene index (MSGI 1.0) was assembled
using the Sanger ESTs available from GenBank, the GS FLX Titanium
EST sequences, and the de novo assembled Illumina sequences. MSGI
1.0 contains 124,025 unique sequences including 22,729 tentative
consensus sequences (TCs), 22,315 singletons and 78,981 pseudo-singletons.
We identified a total of 1,294 simple sequence repeats (SSR) among
the sequences in MSGI 1.0. In addition, a total of 10,826 single
nucleotide polymorphisms (SNPs) were predicted between the two genotypes.
Out of 55 SNPs randomly selected for experimental validation, 47
(85%) were polymorphic between the two genotypes. We also identified
numerous allelic variations within each genotype. Digital gene expression
analysis identified numerous candidate genes that may play a role
in stem development as well as candidate genes that may contribute
to the differences in cell wall composition in stems of the two genotypes.
CONCLUSIONS:Our results demonstrate that RNA-Seq can be successfully
used for gene identification, polymorphism detection and transcript
profiling in alfalfa, a non-model, allogamous, autotetraploid species.
The alfalfa gene index assembled in this study, and the SNPs, SSRs
and candidate genes identified can be used to improve alfalfa as
a forage crop and cellulosic feedstock.},
doi = {10.1186/1471-2164-12-199},
issn = {1471-2164},
pubmedid = {21504589},
url = {http://www.biomedcentral.com/1471-2164/12/199}
}
@ARTICLE{Yang2010a,
author = {Yang, S Samuel and Valdés-López, Oswaldo and Xu, Wayne and Bucciarelli,
Bruna and Gronwald, John and Hernández, Georgina and Vance, Carroll},
title = {Transcript profiling of common bean (Phaseolus vulgaris L.) using
the GeneChip® Soybean Genome Array: optimizing analysis by masking
biased probes},
journal = {BMC Plant Biology},
year = {2010},
volume = {10},
pages = {85},
number = {1},
abstract = {BACKGROUND:Common bean (Phaseolus vulgaris L.) and soybean (Glycine
max) both belong to the Phaseoleae tribe and share significant coding
sequence homology. This suggests that the GeneChip® Soybean Genome
Array (soybean GeneChip) may be used for gene expression studies
using common bean.RESULTS:To evaluate the utility of the soybean
GeneChip for transcript profiling of common bean, we hybridized cRNAs
purified from nodule, leaf, and root of common bean and soybean in
triplicate to the soybean GeneChip. Initial data analysis showed
a decreased sensitivity and accuracy of measuring differential gene
expression in common bean cross-species hybridization (CSH) GeneChip
data compared to that of soybean. We employed a method that masked
putative probes targeting inter-species variable (ISV) regions between
common bean and soybean. A masking signal intensity threshold was
selected that optimized both sensitivity and accuracy of measuring
differential gene expression. After masking for ISV regions, the
number of differentially-expressed genes identified in common bean
was increased by 2.8-fold reflecting increased sensitivity. Quantitative
RT-PCR (qRT-PCR) analysis of 20 randomly selected genes and purine-ureide
pathway genes demonstrated an increased accuracy of measuring differential
gene expression after masking for ISV regions. We also evaluated
masked probe frequency per probe set to gain insight into the sequence
divergence pattern between common bean and soybean. The sequence
divergence pattern analysis suggested that the genes for basic cellular
functions and metabolism were highly conserved between soybean and
common bean. Additionally, our results show that some classes of
genes, particularly those associated with environmental adaptation,
are highly divergent.CONCLUSIONS:The soybean GeneChip is a suitable
cross-species platform for transcript profiling in common bean when
used in combination with the masking protocol described. In addition
to transcript profiling, CSH of the GeneChip in combination with
masking probes in the ISV regions can be used for comparative ecological
and/or evolutionary genomics studies.},
doi = {10.1186/1471-2229-10-85},
issn = {1471-2229},
pubmedid = {20459672},
url = {http://www.biomedcentral.com/1471-2229/10/85}
}
@ARTICLE{Yang2009d,
author = {Yang, S. Samuel and Xu, Wayne Wenzhong and Tesfaye, Mesfin and Lamb,
JoAnn F. S. and Jung, Hans-Joachim G. and Samac, Deborah A. and Vance,
Carroll P. and Gronwald, John W.},
title = {Single-Feature Polymorphism Discovery in the Transcriptome of Tetraploid
Alfalfa},
journal = {The Plant Genome},
year = {2009},
volume = {2},
pages = {224--232},
number = {3},
month = nov,
abstract = {Advances in alfalfa [Medicago sativa (L.) subsp. sativa] breeding,
molecular genetics, and genomics have been slow because this crop
is an allogamous autotetraploid (2n = 4x = 32) with complex polysomic
inheritance and few genomic resources. Increasing cellulose and decreasing
lignin in alfalfa stem cell walls would improve this crop as a cellulosic
ethanol feedstock. We conducted genome-wide analysis of single-feature
polymorphisms (SFPs) of two alfalfa genotypes (252, 1283) that differ
in stem cell wall lignin and cellulose concentrations. SFP analysis
was conducted using the Medicago GeneChip (Affymetrix, Santa Clara,
CA) as a cross-species platform. Analysis of GeneChip expression
data files of alfalfa stem internodes of genotypes 252 and 1283 at
two growth stages (elongating, post-elongation) revealed 10,890 SFPs
in 8230 probe sets. Validation analysis by polymerase chain reaction
(PCR)-sequencing of a random sample of SFPs indicated a 17% false
discovery rate. Functional classification and over-representation
analysis showed that genes involved in photosynthesis, stress response
and cell wall biosynthesis were highly enriched among SFP-harboring
genes. The Medicago GeneChip is a suitable cross-species platform
for detecting SFPs in tetraploid alfalfa.},
url = {http://plantgenome.scijournals.org/cgi/content/abstract/2/3/224}
}
@ARTICLE{Yang2005,
author = {Yang, Sherry X. and Simon, Richard M. and Tan, Antoinette R. and
Nguyen, Diana and Swain, Sandra M.},
title = {Gene Expression Patterns and Profile Changes Pre- and Post-Erlotinib
Treatment in Patients with Metastatic Breast Cancer},
journal = {Clin. Cancer Res.},
year = {2005},
volume = {11},
pages = {6226--6232},
number = {17},
month = sep,
abstract = {Purpose: To delineate gene expression patterns and profile changes
in metastatic tumor biopsies at baseline and 1 month after treatment
with the epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitor erlotinib in patients with metastatic breast cancer. Experimental
Design: Patients were treated with 150 mg of oral erlotinib daily.
Gene expression profiles were measured with Affymetrix U133A GeneChip
and immunohistochemistry was used to validate microarray findings.
Results: Estrogen receptor (ER) status by immunohistochemistry is
nearly coincided with the two major expression clusters determined
by expression of genes using unsupervised hierarchical clustering
analysis. One of 10 patients had an EGFR-positive tumor detected
by both microarray and immunohistochemistry. In this tumor, tissue
inhibitor of metalloproteinases-3 and collagen type 1 {alpha} 2,
which are the EGF-down-regulated growth repressors, were significantly
increased by erlotinib. Gene changes in EGFR-negative tumors are
those of G-protein-linked and cell surface receptor-linked signaling.
Gene ontology comparison analysis pretreatment and posttreatment
in EGFR-negative tumors revealed biological process categories that
have more genes differentially expressed than expected by chance.
Among 495 gene ontology categories, the significant differed gene
ontology groups include G-protein-coupled receptor protein signaling
(34 genes, P = 0.002) and cell surface receptor-linked signal transduction
(74 genes, P = 0.007). Conclusions: ER status reflects the major
difference in gene expression pattern in metastatic breast cancer.
Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive
tumor and on gene ontology biological process categories or genes
that have function in signal transduction in EGFR-negative tumors.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/17/6226}
}
@ARTICLE{Yang2010,
author = {Yang, Thomas J.W. and Lin, Wen-Dar and Schmidt, Wolfgang},
title = {Transcriptional Profiling of the Arabidopsis Iron Deficiency Response
Reveals Conserved Transition Metal Homeostasis Networks},
journal = {Plant Physiology},
year = {2010},
volume = {152},
pages = {2130--2141},
number = {4},
month = apr,
abstract = {Iron (Fe) deficiency is counteracted by a suite of responses to ensure
maintenance of vital processes for which Fe is essential. Here, we
report on transcriptional changes upon Fe deficiency, investigated
in two Arabidopsis (Arabidopsis thaliana) accessions, Columbia (Col-0)
and C24. Functional modules of the Arabidopsis Fe deficiency syndrome
were inferred from clustering of Fe-responsive genes according to
their coexpression. It was found that the redistribution of transition
metals is an integral part of the reduction-based response to Fe
starvation. The differential expression of metal transporters under
the control of the FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION
FACTOR appeared to reflect an anticipated reaction rather than a
response to the actual change in metal distribution. In contrast,
the regulation of the zinc transporters ZRT/IRT-LIKE PROTEIN2 (ZIP2),
ZIP3, ZIP4, and ZIP9 was dependent on the cellular zinc level, and
their regulation by Fe was a secondary effect. Cellular Fe homeostasis
was found to be closely coupled to Fe-related processes in the plastids.
Using clustered genes as bait in gene-fishing experiments, we were
able to attribute potentially important roles for gene candidates
that have no previously described function in the Fe deficiency response.
These results demonstrate a conceptually novel and integrative view
into the regulation and interactions that allow Arabidopsis to adapt
to suboptimal Fe availability.},
url = {http://www.plantphysiol.org/cgi/content/abstract/152/4/2130}
}
@ARTICLE{Yang2011f,
author = {Yang, Xiaofeng S. and Wu, Jingrui and Ziegler, Todd E. and Yang,
Xiao and Zayed, Adel and Rajani, M.S. and Zhou, Dafeng and Basra,
Amarjit S. and Schachtman, Daniel P. and Peng, Mingsheng and Armstrong,
Charles L. and Caldo, Rico A. and Morrell, James A. and Lacy, Michelle
and Staub, Jeffrey M.},
title = {Gene Expression Biomarkers Provide Sensitive Indicators of in Planta
Nitrogen Status in Maize},
journal = {Plant Physiology},
year = {2011},
volume = {157},
pages = {1841-1852},
number = {4},
abstract = {Over the last several decades, increased agricultural production has
been driven by improved agronomic practices and a dramatic increase
in the use of nitrogen-containing fertilizers to maximize the yield
potential of crops. To reduce input costs and to minimize the potential
environmental impacts of nitrogen fertilizer that has been used to
optimize yield, an increased understanding of the molecular responses
to nitrogen under field conditions is critical for our ability to
further improve agricultural sustainability. Using maize (Zea mays)
as a model, we have characterized the transcriptional response of
plants grown under limiting and sufficient nitrogen conditions and
during the recovery of nitrogen-starved plants. We show that a large
percentage (approximately 7%) of the maize transcriptome is nitrogen
responsive, similar to previous observations in other plant species.
Furthermore, we have used statistical approaches to identify a small
set of genes whose expression profiles can quantitatively assess
the response of plants to varying nitrogen conditions. Using a composite
gene expression scoring system, this single set of biomarker genes
can accurately assess nitrogen responses independently of genotype,
developmental stage, tissue type, or environment, including in plants
grown under controlled environments or in the field. Importantly,
the biomarker composite expression response is much more rapid and
quantitative than phenotypic observations. Consequently, we have
successfully used these biomarkers to monitor nitrogen status in
real-time assays of field-grown maize plants under typical production
conditions. Our results suggest that biomarkers have the potential
to be used as agronomic tools to monitor and optimize nitrogen fertilizer
usage to help achieve maximal crop yields.},
doi = {10.1104/pp.111.187898},
eprint = {http://www.plantphysiol.org/cgi/reprint/157/4/1841.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/157/4/1841}
}
@ARTICLE{Yang2011i,
author = {Yang, Yang and Chang, Ti-Cheng and Yasue, Hiroshi and Bharti, Arvind
and Retzel, Ernest and Liu, Wan-Sheng},
title = { ZNF280BY and ZNF280AY: autosome derived Y-chromosome gene families
in Bovidae },
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {13},
number = {1},
abstract = {BACKGROUND:Recent progress in exploring the Y-chromosome gene content
in humans, mice and cats have suggested that "autosome-to-Y" transposition
of the male fertility genes is a recurrent theme during the mammalian
Y-chromosome evolution. These transpositions are lineage-dependent.
The purpose of this study is to investigate the lineage-specific
Y-chromosome genes in bovid.RESULTS:We took a direct testis cDNA
selection strategy and discovered two novel gene families, ZNF280BY
and ZNF280AY, on the bovine (Bos taurus) Y-chromosome (BTAY), which
originated from the transposition of a gene block on the bovine chromosome
17 (BTA17) and subsequently amplified. Approximately 130 active ZNF280BY
loci (and ~240 pseudogenes) and ~130 pseudogenized ZNF280AY copies
are present over the majority of the male-specific region (MSY).
Phylogenetic analysis indicated that both gene families fit with
the "birth-and-death" model of evolution. The active ZNF280BY loci
share high sequence similarity and comprise three major genomic structures,
resulted from insertions/deletions (indels). Assembly of a 1.2 Mb
BTAY sequence in the MSY ampliconic region demonstrated that ZNF280BY
and ZNF280AY, together with HSFY and TSPY families, constitute the
major elements within the repeat units. The ZNF280BY gene family
was found to express in different developmental stages of testis
with sense RNA detected in all cell types of the seminiferous tubules
while the antisense RNA detected only in the spermatids. Deep sequencing
of the selected cDNAs revealed that different loci of ZNF280BY were
differentially expressed up to 60-fold. Interestingly, different
copies of the ZNF280AY pseudogenes were also found to differentially
express up to 10-fold. However, expression level of the ZNF280AY
pseudogenes was almost 6-fold lower than that of the ZNF280BY genes.
ZNF280BY and ZNF280AY gene families are present in bovid, but absent
in other mammalian lineages.CONCLUSIONS:ZNF280BY and ZNF280AY are
lineage-specific, multi-copy Y-gene families specific to Bovidae,
and are derived from the transposition of an autosomal gene block.
The temporal and spatial expression patterns of ZNF280BYs in testis
suggest a role in spermatogenesis. This study offers insights into
the genomic organization of the bovine MSY and gene regulation in
spermatogenesis, and provides a model for studying evolution of multi-copy
gene families in mammals.},
doi = {10.1186/1471-2164-12-13},
issn = {1471-2164},
pubmedid = {21214936},
url = {http://www.biomedcentral.com/1471-2164/12/13}
}
@ARTICLE{Yang2012,
author = {Yi Yang and Rita Ciurlionis and Kenneth Kowalkowski and Kennan C.
Marsh and William M. Bracken and Eric A.G. Blomme},
title = {N-vinylpyrrolidone dimer, a novel formulation excipient, causes hepatic
and thyroid hypertrophy through the induction of hepatic microsomal
enzymes in rats},
journal = {Toxicology Letters},
year = {2012},
volume = {208},
pages = {82 - 91},
number = {1},
abstract = {N-vinylpyrrolidone dimer (VPD) is a novel experimental formulation
excipient intended for preclinical toxicology studies. In a previous
4-week toxicity study, VPD induced dose-dependent hepatocellular
and thyroid gland hypertrophy in Sprague-Dawley (SD) rats. The objectives
of the current investigation were to define the underlying molecular
mechanisms of these changes. Two separate studies were conducted
using male SD rats, daily doses of 300, 1000 or 3000 mg/kg of
VPD, and a positive control (phenobarbital at 75 mg/kg/day):
(1) a 28-day study to monitor thyroid hormone levels after 7 and
28 days of dosing; (2) a 5-day study to evaluate hepatic and thyroid
gland transcriptomic changes, as well as hepatic UGT activity levels.
At VPD dosages of 300 mg/kg/day and higher, 2-fold increases
of serum thyroid stimulating hormone (TSH) levels were observed in
male SD rats after 28 days of dosing, while serum thyroxine (T4)
and triiodothyronine (T3) levels were unchanged. Liver UGT enzyme
activity levels were increased in VPD-treated rats after 5 days.
In addition, in the 5-day study, VPD caused increased hepatic mRNA
levels of a panel of drug metabolizing enzymes (DMEs) and transporters,
including Cyp3a1, Cyp2b1, Ugt 2b1, and Abcc3. Similar patterns of
induction were observed in primary rat hepatocytes exposed to VPD.
Transcriptomic changes in the thyroid gland were identified for genes
involved in thyroid hormone biosynthesis and in the FAK, PTEN, and
Wnt/β-catenin signaling pathways. Collectively, these data indicate
that VPD acts as an inducer of hepatic DMEs in SD rats and that this
likely leads to enhanced peripheral metabolism of T3/T4, resulting
in a feedback response characterized by increased serum TSH levels,
and thyroid gland hypertrophy and hyperplasia.},
doi = {10.1016/j.toxlet.2011.10.012},
issn = {0378-4274},
keywords = {Thyroid gland hypertrophy},
url = {http://www.sciencedirect.com/science/article/pii/S0378427411015797}
}
@ARTICLE{Yang2010b,
author = {Yang, Yi and Dahly-Vernon, Annette J. and Blomme, Eric A.G. and Lai-Zhang,
Jie and Kempf, Dale J. and Marsh, Kennan C. and Harrington, Yvette
A. and Nye, Steven H. and Evans, Darin L. and Roman, Richard J. and
Jacob, Howard J. and Waring, Jeffrey F.},
title = {Liver transcriptomic changes associated with ritonavir-induced hyperlipidemia
in sensitive and resistant strains of rats},
journal = {The Veterinary Journal},
year = {2010},
volume = {185},
pages = {75--82},
number = {1},
month = jul,
abstract = {Ritonavir (RTV) and other protease inhibitors (PIs) used for the treatment
of human immunodeficiency virus (HIV) infection are associated with
elevated serum triglycerides (TG) and cholesterol in some patients.
A rat strain (Sprague-Dawley or SD) commonly used in toxicology studies
is not sensitive to RTV-induced hyperlipidemia, making mechanistic
studies and the identification of novel, lipid-neutral PIs challenging.
The objective of this study was to identify a rat strain that mirrors
human PI-associated hyperlipidemia. RTV was administered at 100 mg/kg/day
for 5 days to a panel of 14 rat strains estimated to cover approximately
86% of the known genetic variance in rats. Increased serum TG and
cholesterol levels occurred only in two rat strains, including LEW × BN
rats. Livers from LEW × BN (sensitive) and SD (resistant) rats were
then evaluated using microarrays to investigate differences in the
transcriptomic response to RTV. Several genes, including some involved
in bile acid biosynthesis, gluconeogenesis, and carbohydrate metabolism,
were differentially regulated between the two strains. In particular,
cytochrome P450 7A1 (CYP7A1), a key enzyme for cholesterol metabolism,
was down-regulated in the sensitive and up-regulated in resistant
rats. Collectively, these results demonstrate the utility of a genetically
diverse rat panel to identify strains with clinical relevance for
a particular adverse effect. Furthermore, the genome-wide transcriptomic
analysis suggests that RTV-induced hyperlipidemia is at least in
part due to changes in hepatic lipid biosynthesis and metabolism.
These findings will facilitate the discovery of novel, lipid-neutral
HIV PIs and the identification of relevant biomarkers for this adverse
event.},
booktitle = {Special Issue: Biomarkers in Veterinary Medicine},
issn = {1090-0233},
keywords = {Ritonavir, Lipids, Gene expression, Liver, Rat, Biomarkers},
url = {http://www.sciencedirect.com/science/article/B6WXN-504TPC2-1/2/1ec04062c7300f8893ade3774aecb5ab}
}
@ARTICLE{Yang2008b,
author = {Yang, YQ and Zhang, W and Zhang, BF and Gao, HJ and Zhang, QH},
title = {Establishment of the pipeline for RNA quality assessment from the
cells obtained by laser capture microdissection},
journal = {Yi Chuan},
year = {2008},
volume = {30},
pages = {1521-6--},
number = {11},
month = nov,
abstract = {We developed a standard protocol for quality assessment of low amount
RNA from the cells obtained by laser capture microdissection (LCM).
Three gastric noncancerous tissues were cryo-sectioned, stained with
Cresyl Violet, and pathologically rechecked. Epithelial cells were
obtained by LCM and RNA was isolated. Agilent 2100 bioanalyzer was
used to check the RNA quality. To validate the results from 2100
bioanalyzer, RT-PCR was performed with six genes at both 5'and 3'
end-regions of different abundance (EF1A and ATCB of high abundance,
GAPDH and B2M of moderate abundance, and MED1 and CK20 of low abundance).
RT-PCR analysis of 3 good quality RNAs from cultured cell lines and
3 poor quality RNAs from gastric noncancerous tissues showed high
correlations with that from 2100 bioanalyzer. In conclusion, the
pipeline for low amount RNA quality assessment by RT-PCR from tissue
cryo-section, pathological recheck, LCM purification and RNA isolation
is applicable as a routine method in cancer genome research.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19073563}
}
@ARTICLE{Yang2009e,
author = {Yang, Zhaoqing and Gagarin, Dmitry and St. Laurent, Georges, III
and Hammell, Neil and Toma, Ian and Hu, Chien-an and Iwasa, Ayaka
and McCaffrey, Timothy A.},
title = {Cardiovascular Inflammation and Lesion Cell Apoptosis: A Novel Connection
via the Interferon-Inducible Immunoproteasome},
journal = {Arterioscler Thromb Vasc Biol},
year = {2009},
volume = {29},
pages = {1213--1219},
number = {8},
month = aug,
abstract = {Objective-- Increasing evidence suggests that chronic inflammation
contributes to atherogenesis, and that acute inflammatory events
cause plaque rupture, thrombosis, and myocardial infarction. The
present studies examined how inflammatory factors, such as interferon-{gamma}
(IFN{gamma}), cause increased sensitivity to apoptosis in vascular
lesion cells. Methods and Results-- Cells from the fibrous cap of
human atherosclerotic lesions were sensitized by interferon-{gamma}
(IFN{gamma}) to Fas-induced apoptosis, in a Bcl-XL reversible manner.
Microarray profiling identified 72 INF{gamma}-induced transcripts
with potential relevance to apoptosis. Half could be excluded because
they were induced by IRF-1 overexpression, which did not sensitize
to apoptosis. IFN{gamma} treatment strongly reduced Mcl-1, phospho-Bcl-2
(ser70), and phospho-Bcl-XL (ser62) protein levels. Candidate transcripts
were modulated by siRNA, overexpression, or inhibitors to assess
the effect on IFN{gamma}-induced Fas sensitivity. Surprisingly, siRNA
knockdown of PSMB8 (LMP7), an "immunoproteasome" component, reversed
IFN{gamma}-induced sensitivity to Fas ligation and prevented Fas/IFN{gamma}-induced
degradation of Mcl-1, but did not protect p-Bcl-2 or p-Bcl-XL. Proteasome
inhibition markedly increased Mcl-1, p-Bcl-2, and p-Bcl-XL levels
after IFN{gamma} treatment. Conclusions-- Although critical for antigen
presentation, the immunoproteasome appears to be a key link between
inflammatory factors and the control of vascular cell apoptosis and
may thus be an important factor in plaque rupture and myocardial
infarction. Cells from human atherosclerotic lesions are sensitized
by IFN{gamma} to Fas-induced apoptosis. Microarrays identified 72
IFN{gamma}-induced transcripts relevant to apoptosis. siRNA knockdown
of PSMB8 (LMP7), an "immunoproteasome" component, reversed IFN{gamma}-induced
sensitivity and prevented degradation of Mcl-1, a potent survival
factor. The immunoproteasome may link inflammation to vascular cell
apoptosis.},
url = {http://atvb.ahajournals.org/cgi/content/abstract/29/8/1213}
}
@ARTICLE{Yang2007a,
author = {Yang, Zhiyong and Quigley, Harry A. and Pease, Mary E. and Yang,
Yanqin and Qian, Jiang and Valenta, Danielle and Zack, Donald J.},
title = {Changes in Gene Expression in Experimental Glaucoma and Optic Nerve
Transection: The Equilibrium between Protective and Detrimental Mechanisms},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {5539--5548},
number = {12},
month = dec,
abstract = {PURPOSE. The authors studied retinal gene expression changes in rats
after experimental intraocular pressure elevation and optic nerve
transection to elucidate molecular mechanisms of retinal ganglion
cell (RGC) death. METHODS. Translimbal laser photocoagulation was
used to induce unilateral IOP elevation in 41 albino Wistar rats.
In 38 additional animals, unilateral transection of the optic nerve
was performed. Retinas were harvested 1 day, 3 days, 1 week, 2 weeks,
4 weeks, and 8 weeks after each treatment, and total RNA was isolated.
Pooled RNA from each time point was analyzed with rat genome arrays.
Array results were confirmed by real-time PCR, and localization studies
were performed using in situ hybridization for select genes. RESULTS.
Genes that were upregulated in glaucoma, but not after transection,
included Cyclin D2, Stat1, Stat3, c-Fos, Junb, Anxa1, Anxa 3, and
CCAAT/enhancer binding protein (Cebp-delta). In glaucoma and transection
models, the upregulation of c-Jun, Activating transcription factor
3, Heat shock protein 27, and Timp1 were observed. Comparisons among
microarray databases were performed between our data and reports
of retinal and optic nerve injury models in mice, rats, and monkeys.
CONCLUSIONS. Gene expression changes specific to experimental glaucoma
injury were identified. The present analysis supports the importance
of neuroinflammation and the participation of the tumor necrosis
factor alpha signaling pathway in glaucoma injury. The alterations
observed include processes that are both protective of and detrimental
to the survival of RGCs.},
url = {http://www.iovs.org/cgi/content/abstract/48/12/5539}
}
@ARTICLE{Yant2010,
author = {Yant, Levi and Mathieu, Johannes and Dinh, Thanh Theresa and Ott,
Felix and Lanz, Christa and Wollmann, Heike and Chen, Xuemei and
Schmid, Markus},
title = {Orchestration of the Floral Transition and Floral Development in
Arabidopsis by the Bifunctional Transcription Factor APETALA2},
journal = {PLANT CELL},
year = {2010},
volume = {22},
pages = {2156--2170},
number = {7},
month = jul,
abstract = {The Arabidopsis thaliana transcription factor APETALA2 (AP2) has numerous
functions, including roles in seed development, stem cell maintenance,
and specification of floral organ identity. To understand the relationship
between these different roles, we mapped direct targets of AP2 on
a genome-wide scale in two tissue types. We find that AP2 binds to
thousands of loci in the developing flower, many of which exhibit
AP2-dependent transcription. Opposing, logical effects are evident
in AP2 binding to two microRNA genes that influence AP2 expression,
with AP2 positively regulating miR156 and negatively regulating miR172,
forming a complex direct feedback loop, which also included all but
one of the AP2-like miR172 target clade members. We compare the genome-wide
direct target repertoire of AP2 with that of SCHLAFMUTZE, a closely
related transcription factor that also represses the transition to
flowering. We detect clear similarities and important differences
in the direct target repertoires that are also tissue specific. Finally,
using an inducible expression system, we demonstrate that AP2 has
dual molecular roles. It functions as both a transcriptional activator
and repressor, directly inducing the expression of the floral repressor
AGAMOUS-LIKE15 and directly repressing the transcription of floral
activators like SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1.},
url = {http://www.plantcell.org/cgi/content/abstract/22/7/2156}
}
@ARTICLE{Yao2008,
author = {Yao, En-Hui and Fukuda, Noboru and Ueno, Takahiro and Matsuda, Hiroyuki
and Matsumoto, Koichi and Nagase, Hiroki and Matsumoto, Yoshiaki
and Takasaka, Ayako and Serie, Kazuo and Sugiyama, Hiroshi and Sawamura,
Tatsuya},
title = {Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Lectin-Like
Oxidized Low-Density Lipoprotein Receptor-1 Attenuates Restenosis
of the Artery After Injury},
journal = {Hypertension},
year = {2008},
volume = {52},
pages = {86--92},
number = {1},
month = jul,
abstract = {Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is
a membrane protein that can support the binding, internalization,
and proteolytic degradation of oxidized low-density lipoprotein.
The LOX-1 expression increases in the neointima after balloon injury.
To develop an efficient compound to inhibit LOX-1, we designed and
synthesized a novel gene silencer pyrrole-imidazole (PI) polyamide
targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) to
the activator protein-1 binding site. We examined the effects of
PI polyamide to LOX-1 on the LOX-1 promoter activity, the expression
of LOX-1 mRNA and protein, and neointimal hyperplasia of the rat
carotid artery after balloon injury. PI polyamide to LOX-1 significantly
inhibited the rat LOX-1 promoter activity and decreased the expression
of LOX-1 mRNA and protein. After balloon injury of the arteries,
PI polyamide to LOX-1 was incubated for 10 minutes. Fluorescein isothiocyanate-labeled
PI polyamide was distributed to almost all of the nuclei in the injured
artery. PI polyamide to LOX-1 (100 {micro}g) significantly inhibited
the neointimal thickening by 58%. PI polyamide preserved the re-endothelialization
in the injured artery. PI polyamide significantly inhibited the expression
of LOX-1, monocyte chemoattractant protein-1, intercellular adhesion
molecule-1, and matrix metalloproteinase-9 mRNAs in the injured artery.
The synthetic PI polyamide to LOX-1 decreased the expression of LOX-1
and inhibited neointimal hyperplasia after arterial injury. This
novel gene silencer PI polyamide to LOX-1 is, therefore, considered
to be a feasible agent for the treatment of in-stent restenosis.},
url = {http://hyper.ahajournals.org/cgi/content/abstract/52/1/86}
}
@ARTICLE{Yao2009,
author = {Yao, En-Hui and Fukuda, Noboru and Ueno, Takahiro and Matsuda, Hiroyuki
and Nagase, Hiroki and Matsumoto, Yoshiaki and Sugiyama, Hiroshi
and Matsumoto, Koichi},
title = {A pyrrole-imidazole polyamide targeting transforming growth factor-{beta}1
inhibits restenosis and preserves endothelialization in the injured
artery},
journal = {Cardiovasc Res},
year = {2009},
volume = {81},
pages = {797--804},
number = {4},
month = mar,
abstract = {AimsAlthough the use of drug-eluting stents (DESs) has been shown
to limit neointima hyperplasia, currently available DESs may adversely
affect re-endothelialization. To evaluate whether a novel gene silencer
pyrrole-imidazole (PI) polyamide targeting transforming growth factor
(TGF)-{beta}1 is a candidate agent for the DESs, we examined the
effects of PI polyamide targeting the TGF-{beta}1 promoter on neointimal
formation in rat carotid artery after balloon injury. Methods and
resultsPI polyamide was designed to span the boundary of the AP-1
binding site of the TGF-{beta}1 promoter. After inducing balloon
injury to arteries, incubation with PI polyamide was carried out
for 10 min. Neointimal thickening and re-endothelialization were
evaluated at 21 days after injury. Fluoresceinisothiocyanate-labelled
PI polyamide was distributed into most of the nuclei in the injured
artery without any delivery reagents. PI polyamide (100 {micro}g)
significantly inhibited neointimal thickening at 21 days after injury
by 57%. PI polyamide targeting TGF-{beta}1 significantly decreased
the expression of TGF-{beta}1 mRNA and protein in the artery at 3
days after injury and also suppressed the expression of connective
tissue growth factor (CTGF), fibronectin, collagen type 1, and lectin-like
ox-LDL receptor-1 mRNAs. A morphometric analysis showed that PI polyamide
targeting TGF-{beta}1 accelerated re-endothelialization in the injured
artery. ConclusionThese findings suggest that the synthetic PI polyamide
targeting the TGF-{beta}1 promoter may have the potential to suppress
neointimal hyperplasia after arterial injury by the down-regulation
of TGF-{beta}1 and CTGF and the reduction of the extracellular matrix.
As a result, PI polyamide targeting TGF-{beta}1 may therefore be
a potentially effective agent for the treatment of in-stent restenosis,
as a candidate agent for the next-generation DES.},
url = {http://cardiovascres.oxfordjournals.org/cgi/content/abstract/81/4/797}
}
@ARTICLE{Yao2008a,
author = {Yao, En-Hui and Fukuda, Noboru and Ueno, Takahiro and Tsunemi, Akiko
and Endo, Morito and Matsumoto, Koichi},
title = {Complement 3 activates the KLF5 gene in rat vascular smooth muscle
cells},
journal = {Biochemical and Biophysical Research Communications},
year = {2008},
volume = {367},
pages = {468--473},
number = {2},
month = mar,
abstract = {We have shown that spontaneously hypertensive rat (SHR)-derived vascular
smooth muscle cells (VSMCs) change to the synthetic phenotype and
show increased expression of complement 3 (C3) and that C3 plays
a role in the change to the synthetic phenotype. To determine the
mechanisms underlying the effects of C3 on this phenotypic change,
we examined the effects of C3a on transcription factors involved
in VSMC phenotype and found that C3a increased the expression of
Krüppel-like zinc-finger transcription factor 5 (KLF5) mRNA. C3a
increased KLF5 promoter activity in a concentration-dependent manner.
Deletion analysis of the promoter region of the KLF5 gene revealed
that the region between nucleotides-991 and -699 contains the transcriptional
regulatory element stimulated by C3a. C3a induced extracellular signal-regulated
kinase (ERK) phosphorylation, and C3a-increased KLF5 promoter activity
was completely inhibited by the MEK inhibitor U0126. These findings
suggest that C3 increases KLF5 promoter activity and gene expression
via ERK signaling.},
issn = {0006-291X},
keywords = {Complement 3, KLF5, ERK, Rat, VSMC},
url = {http://www.sciencedirect.com/science/article/B6WBK-4RH8R5M-B/2/ed9254e7f920d91c1701c16516a1b98d}
}
@ARTICLE{Yao2005,
author = {Yao, Fayi and Yu, Fei and Gong, Lijie and Taube, David and Rao, Donald
D. and MacKenzie, Robert G.},
title = {Microarray analysis of fluoro-gold labeled rat dopamine neurons harvested
by laser capture microdissection},
journal = {Journal of Neuroscience Methods},
year = {2005},
volume = {143},
pages = {95--106},
number = {2},
month = apr,
abstract = {The cellular heterogeneity of brain tissue presents a challenge to
gene expression profiling of specific neuronal cell types. The present
study employed a fluorescent neural tracer to specifically label
midbrain dopamine neurons and non-dopamine cortical neurons. The
labeled cells were then used to visually guide harvesting of the
cells by laser capture microdissection (LCM). RNA extracted from
the two populations of harvested cells was then amplified, labeled
and co-hybridized to high density cDNA microarrays for two-color
differential expression profiling. Many of the genes most highly
enriched in the dopamine neurons were found to be genes previously
known to define the dopamine neuronal phenotype. However, results
from the microarray were only partially validated by quantitative
RT-PCR analysis. The results indicate that LCM harvesting of specific
neuronal phenotypes can be effectively guided in a complex cellular
environment by specific pre-labeling of the target cell populations
and underlie the importance of independent validation of microarray
results.},
issn = {0165-0270},
keywords = {Microarray, Laser capture microdissection, Dopamine neurons},
url = {http://www.sciencedirect.com/science/article/B6T04-4DX27FD-2/2/0b1fe57783839f1b517b93c439640998}
}
@ARTICLE{Yao2009a,
author = {Yao, Hang and Felfly, Hady and Wang, Juan and Zhou, Dan and Haddad,
Gabriel G.},
title = {DIDS protects against neuronal injury by blocking Toll-like receptor
2 activated-mechanisms},
journal = {Journal of Neurochemistry},
year = {2009},
volume = {108},
pages = {835--846},
number = {3},
abstract = {Abstract Using an in vitro ischemia model (ischemic solution; IS model)
that induces penumbral cell death, we examined the effect of 4,4′-diisothio-cyanostilbene-2,2′-disulfonic
acid (DIDS) on cell injury/death and underlying molecular mechanisms.
Propidium iodide (PI) uptake was used to quantify cell death in organotypic
hippocampal slice cultures. A 24-h IS exposure caused a fivefold
increase in mean PI fluorescence intensity. DIDS, dose-dependently
(1–4000 μM), reduced the IS-induced PI uptake in hippocampal
CA1 neurons with an IC50 of 26 μM. This protective effect of DIDS
was reversible and effective even 6Â h following the onset of IS
treatment. Gene expression profiling studies indicated that among
∼46 000 transcripts tested, the most significantly up-regulated
gene by IS was interleukin-1β (IL-1β) which was also the most significantly
down-regulated gene when DIDS was added to the IS-treated slices.
The addition of a recombinant IL-1 receptor antagonist (100 μg/mL)
or neutralizing IL-1β antibody significantly attenuated the IS-induced
cell death, indicating that the up-regulation of IL-1β with IS treatment
contributed to the IS-induced cell death. Toll-like receptor 2 (TLR2),
another gene that was significantly up-regulated by IS and suppressed
by DIDS, was studied to determine whether it was related to the IL-1β
up-regulation. Indeed, this was the case as the IS-induced IL-1β
up-regulation was abolished in TLR2−/− mouse brain slices. Furthermore,
the IS-induced cell death was significantly reduced in TLR2−/−
when compared with that in wild-type slices, indicating that TLR2
is functionally upstream of IL-1β in this IS model. We conclude
that (i) IS up-regulates TLR2 expression and augments TLR2 signaling,
causing over-expression of IL-1β which leads to cell death and (ii)
DIDS blocks IS-induced neuronal injury, at least partially, by suppressing
the TLR2 pathway.},
issn = {1471-4159},
keywords = {gene expression, ischemia, penumbra, slice culture},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1471-4159.2008.05838.x}
}
@ARTICLE{Yao2011,
author = {Yao, Liping and Liu, Fei and Hong, Liu and Sun, Li and Liang, Shuhui
and Wu, Kaichun and Fan, Daiming},
title = {The function and mechanism of COX-2 in angiogenesis of gastric cancer
cells},
journal = {Journal of Experimental \& Clinical Cancer Research},
year = {2011},
volume = {30},
pages = {13},
number = {1},
abstract = {BACKGROUND:Here we aimed to investigate the effect of COX-2 siRNA
on proliferation and angiogenesis of gastric cancer cells.METHODS:The
gastric cancer cell line SGC7901 was transfected with COX-2 siRNA,
then the growth and angiogenesis of cells were detected by in vitro
and in vivo assay. Human microarray, RT-PCR and western blot were
used to identify differentially expressed angiogenesis-related molecules
in cells with decreased expression of COX-2.RESULTS:Down-regulation
of COX-2 could significantly inhibit the in vitro and in vivo growth
of gastric cancer cells, and suppress the migration and tube formation
of human umbilical vein endothelial cells. Totally 23 angiogenesis-related
molecules were found involved in COX-2-induced angiogenesis suppression.
The results of RT-PCR and western blot showed that down-regulation
of COX-2 might inhibit VEGF, Flt-1, Flk-1/KDR, angiopoietin-1, tie-2,
MMP2 and OPN.CONCLUSIONS:COX-2 might mediate tumor angiogenesis and
growth, and could be considered as a target for gastric cancer therapy.},
doi = {10.1186/1756-9966-30-13},
issn = {1756-9966},
pubmedid = {21266034},
url = {http://www.jeccr.com/content/30/1/13}
}
@ARTICLE{Yao2003,
author = {Yao, Mylene W. M. and Lim, Hyunjung and Schust, Daniel J. and Choe,
Sung E. and Farago, Anna and Ding, Yueyun and Michaud, Sebastien
and Church, George M. and Maas, Richard L.},
title = {Gene Expression Profiling Reveals Progesterone-Mediated Cell Cycle
and Immunoregulatory Roles of Hoxa-10 in the Preimplantation Uterus},
journal = {Mol. Endocrinol.},
year = {2003},
volume = {17},
pages = {610--627},
number = {4},
month = apr,
abstract = {Human infertility and recurrent pregnancy loss caused by implantation
defects are poorly understood. Hoxa-10-deficient female mice have
severe infertility and recurrent pregnancy loss due to defective
uterine implantation. Gene expression profiling experiments reveal
that Hoxa-10 is an important regulator of two critical events in
implantation: stromal cell proliferation and local immunosuppression.
At the time of implantation, Hoxa-10 mediates the progesterone-stimulated
proliferation of uterine stromal cells. Hoxa-10 mutants express a
stromal cell proliferation defect that is accompanied by quantitative
or spatial alterations in the expression of two cyclin-dependent
kinase inhibitor genes, p57 and p15. Hoxa-10 deficiencyFS also leads
to a severe local immunological disturbance, characterized by a polyclonal
proliferation of T cells, that occurs in place of the normal progesterone-mediated
immunosuppression in the periimplantation uterus.},
url = {http://mend.endojournals.org/cgi/content/abstract/17/4/610}
}
@ARTICLE{Yao2010,
author = {Yao, Sheng and Bee, Alix and Brewer, Daniel and Dodson, Andrew and
Beesley, Carol and Ke, Youqiang and Ambroisine, Laurence and Fisher,
Gabrielle and Moller, Heinrich and Dickinson, Tim and Gerard, Patricia
and Lian, Lu-Yu and Risk, Janet and Lane, Brian and Smith, Paul and
Reuter, Victor and Berney, Daniel and Gosden, Christine and Scardino,
Peter and Cuzick, Jack and Djamgoz, Mustafa B.A. and Cooper, Colin
and Foster, Christopher S.},
title = {PRKC-{zeta} Expression Promotes the Aggressive Phenotype of Human
Prostate Cancer Cells and Is a Novel Target for Therapeutic Intervention},
journal = {Genes \& Cancer},
year = {2010},
volume = {1},
pages = {444--464},
number = {5},
month = may,
abstract = {We show protein kinase C-zeta (PKC-{zeta}) to be a novel predictive
biomarker for survival from prostate cancer (P < 0.001). We also
confirm that transcription of the PRKC-{zeta} gene is crucial to
the malignant phenotype of human prostate cancer. Following siRNA
silencing of PRKC-{zeta} in PC3-M prostate cancer cells, stable transfectant
cell line si-PRKC-{zeta}-PC3-MT1-6 is phenotypically nonmalignant
in vitro and in vivo. Genome-wide expression analysis identified
373 genes to be differentially expressed in the knockdown cells and
4 key gene networks to be significantly perturbed during phenotype
modulation. Functional interconnection between some of the modulated
genes is revealed, although these may be within different regulatory
pathways, emphasizing the complexity of their mutual interdependence.
Genes with altered expression following PRKC-{zeta} knockdown include
HSPB1, RAD51, and ID1 that we have previously described to be critical
in prostatic malignancy. Because expression of PRKC-{zeta} is functionally
involved in promoting the malignant phenotype, we propose PKC-{zeta}
as a novel and biologically relevant target for therapeutic intervention
in prostate cancer.},
url = {http://gan.sagepub.com/cgi/content/abstract/1/5/444}
}
@ARTICLE{Yao2010a,
author = {Yao, Xianglan and Fredriksson, Karin and Yu, Zu-Xi and Xu, Xiuli
and Raghavachari, Nalini and Keeran, Karen J. and Zywicke, Gayle
J. and Kwak, Minjung and Amar, Marcelo J. A. and Remaley, Alan T.
and Levine, Stewart J.},
title = {Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma
via a Low-Density Lipoprotein Receptor-mediated Pathway},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2010},
volume = {182},
pages = {1228--1238},
number = {10},
month = nov,
abstract = {Rationale: Distinct sets of corticosteroid-unresponsive genes modulate
disease severity in asthma. Objectives: To identify corticosteroid-unresponsive
genes that provide new insights into disease pathogenesis and asthma
therapeutics. Methods: Experimental murine asthma was induced by
nasal administration of house dust mite for 5 days per week. Dexamethasone
and apolipoprotein E (apo E) mimetic peptides were administered via
osmotic minipumps. Measurements and Main Results: Genome-wide expression
profiling of the lung transcriptome in a house dust mite-induced
model of murine asthma identified increases in apo E mRNA levels
that persisted despite corticosteroid treatment. House dust mite-challenged
apo E-/- mice displayed enhanced airway hyperreactivity and goblet
cell hyperplasia, which could be rescued by administration of an
apo E(130-149) mimetic peptide. Administration of the apo E(130-149)
mimetic peptide to house dust mite-challenged apo E-/- mice also
inhibited eosinophilic airway inflammation, IgE production, and the
expression of Th2 and Th17 cytokines. House dust mite-challenged
low-density lipoprotein receptor (LDLR) knockout mice displayed a
similar phenotype as apo E-/- mice with enhanced airway hyperreactivity,
goblet cell hyperplasia, and mucin gene expression, but could not
be rescued by the apo E(130-149) mimetic peptide, consistent with
a LDLR-dependent mechanism. Conclusions: These findings for the first
time identify an apo E-LDLR pathway as an endogenous negative regulator
of airway hyperreactivity and goblet cell hyperplasia in asthma.
Furthermore, our results demonstrate that strategies that activate
the apo E-LDLR pathway, such as apo E mimetic peptides, might be
developed into a novel treatment approach for patients with asthma.},
comment = {10.1164/rccm.201002-0308OC},
url = {http://ajrccm.atsjournals.org/cgi/content/abstract/182/10/1228}
}
@ARTICLE{Yao2007,
author = {Yao, Xiao-Dan and Fernandez, Sherie and Kelly, Margaret M. and Kaushic,
Charu and Rosenthal, Kenneth L.},
title = {Expression of Toll-like receptors in murine vaginal epithelium is
affected by the estrous cycle and stromal cells},
journal = {Journal of Reproductive Immunology},
year = {2007},
volume = {75},
pages = {106--119},
number = {2},
month = oct,
abstract = {Vaginal epithelium is regulated by female sex hormones and serves
as the first line of innate immune defense against sexually transmitted
infections (STIs). This occurs in part through recognition of pathogens
via Toll-like receptors (TLRs); however, the expression and role
of TLRs in reproductive tract immunity are poorly understood. Here,
we have compared the effect of the estrous cycle and treatment with
DepoProvera (Depo) on TLR mRNA expression in whole mouse vaginal
tissue, vaginal epithelium isolated using laser capture microdissection
(LCM) and in primary vaginal epithelial cells (ECs) grown in vitro.
Distinct patterns of TLR expression were observed in LCM-isolated
vaginal epithelium versus whole vaginal tissue. Absolute quantitative
RT-PCR of LCM vaginal epithelium showed that expression of all TLRs,
except TLR11, was significantly increased during the diestrus phase
or following Depo-treatment. TLR2 mRNA showed an extraordinary increase
in expression in both diestrus and following Depo-treatment (23-fold)
over that in the estrus phase. Although TLR2 protein was expressed
at similar levels over the estrous cycle in whole vaginal tissue,
full-length TLR2 protein was only detected during diestrus or after
Depo-treatment in LCM-isolated vaginal epithelium. Distinct TLR mRNA
expression profiles were seen also in primary vaginal ECs in vitro
and only expression of TLR2 was significantly decreased in ECs cultured
in the presence of stromal cells. Thus, TLR expression in vaginal
ECs is regulated by sex hormones and can be affected by stromal cells.
These findings contribute to our understanding of innate immune defense
against STIs and enhance the quality of woman's reproductive health.},
issn = {0165-0378},
keywords = {Mucosa, Vaginal epithelial cells, Stromal cells, Toll-like receptors,
Innate immunity, Estrous cycle},
url = {http://www.sciencedirect.com/science/article/B6T8W-4P0N1TD-1/2/a7c3c8140b53d5fe1701cc6cc4e3e416}
}
@ARTICLE{Yao-Borengasser2008,
author = {Yao-Borengasser, Aiwei and Rassouli, Negah and Varma, Vijayalakshmi
and Bodles, Angela M. and Rasouli, Neda and Unal, Resat and Phanavanh,
Bounleut and Ranganathan, Gouri and McGehee, Robert E., Jr. and Kern,
Philip A.},
title = {Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases after
Pioglitazone Treatment and Is Associated with Peroxisomal Proliferator-Activated
Receptor-{gamma} Responsiveness},
journal = {J. Clin. Endocrinol. Metab.},
year = {2008},
volume = {93},
pages = {4431--4439},
number = {11},
month = nov,
abstract = {Context and Objective: Stearoyl-coenzyme A desaturase (SCD1) is the
rate-limiting enzyme that converts palmitoyl- and stearoyl-coenzyme
A to palmitoleoyl- and oleoyl-cownzyme A, respectively. SCD-deficient
mice are protected from obesity, and the ob/ob mouse has high levels
of SCD. This study was designed to better characterize SCD1 gene
and protein expression in humans with varying insulin sensitivity.
Design, Participants, and Setting: In a university hospital clinical
research center setting, SCD1 gene expression was measured in sc
adipose and vastus lateralis muscle of 86 nondiabetic subjects; 10
wk of pioglitazone (45 mg daily) and metformin (1000 mg twice daily)
treatment were assessed in 36 impaired glucose-tolerant subjects.
Adipocytes were treated with pioglitazone, and SCD1 expression was
attenuated with small interfering RNA (siRNA) to examine other adipocyte
genes. Results: There was no significant relationship between adipose
or muscle SCD1 mRNA and either body mass index or insulin sensitivity.
After pioglitazone (but not metformin) treatment, there was a 2-fold
increase in SCD1 mRNA and protein in adipose tissue. Pioglitazone
also increased SCD1 in vitro. There were significant positive correlations
between SCD1 and peroxisomal proliferator-activated receptor {gamma}
(PPAR{gamma}) as well as other PPAR{gamma}-responsive genes, including
lipin-{beta}, AGPAT2, RBP4, adiponectin receptors, CD68, and MCP1.
When SCD1 expression was inhibited with a siRNA, lipin-{beta}, AGPAT2,
and the adiponectin R2 receptor expression were decreased, and adipocyte
MCP-1 was increased. Conclusions: SCD1 is closely linked to PPAR{gamma}
expression in humans, and is increased by PPAR{gamma} agonists. The
change in expression of some downstream PPAR{gamma} targets after
SCD1 knockdown suggests that PPAR{gamma} up-regulation of SCD1 leads
to increased lipogenesis and potentiation of adiponectin signaling.},
url = {http://jcem.endojournals.org/cgi/content/abstract/93/11/4431}
}
@ARTICLE{Yao-Borengasser2007,
author = {Yao-Borengasser, Aiwei and Varma, Vijayalakshmi and Bodles, Angela
M. and Rasouli, Neda and Phanavanh, Bounleut and Lee, Mi-Jeong and
Starks, Tasha and Kern, Leslie M. and Spencer, Horace J., III and
Rashidi, Amir Adel and McGehee, Robert E., Jr. and Fried, Susan K.
and Kern, Philip A.},
title = {Retinol Binding Protein 4 Expression in Humans: Relationship to Insulin
Resistance, Inflammation, and Response to Pioglitazone},
journal = {J. Clin. Endocrinol. Metab.},
year = {2007},
volume = {92},
pages = {2590--2597},
number = {7},
month = jul,
abstract = {Context: Retinol binding protein 4 (RBP4) was recently found to be
expressed and secreted by adipose tissue, and was strongly associated
with insulin resistance. Objective: The aim was to determine the
relationship between RBP4 and obesity, insulin resistance, and other
markers of insulin resistance in humans. Design and Patients: RBP4
mRNA levels in adipose tissue and muscle of nondiabetic human subjects
with either normal or impaired glucose tolerance (IGT) were studied,
along with plasma RBP4. RBP4 gene expression was also measured in
adipose tissue fractions, and from visceral and sc adipose tissue
(SAT) from surgical patients. Setting: The study was conducted at
University Hospital and General Clinical Research Center. Intervention:
Insulin sensitivity (SI) was measured, and fat and muscle biopsies
were performed. In IGT subjects, these procedures were performed
before and after treatment with metformin or pioglitazone. Main Outcome
Measures: The relationship between RBP4 expression and obesity, SI,
adipose tissue inflammation, and intramyocellular lipid level, and
response to insulin sensitizers was measured. Results: RBP4 was expressed
predominantly from the adipocyte fraction of SAT. Although SAT RBP4
expression and the plasma RBP4 level demonstrated no significant
relationship with body mass index or SI, there was a strong positive
correlation between RBP4 mRNA and adipose inflammation (monocyte
chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA.
Treatment of IGT subjects with pioglitazone resulted in an increase
in SI and an increase in RBP4 gene expression in both adipose tissue
and muscle, but not in plasma RBP4 level, and the in vitro treatment
of cultured adipocytes with pioglitazone yielded a similar increase
in RBP4 mRNA. Conclusions: RBP4 gene expression in humans is associated
with inflammatory markers, but not with insulin resistance. The increase
in RBP4 mRNA after pioglitazone treatment is unusual, suggesting
a complex regulation of this novel adipokine.},
url = {http://jcem.endojournals.org/cgi/content/abstract/92/7/2590}
}
@ARTICLE{Yao-Borengasser2011,
author = {Aiwei Yao-Borengasser and Vijayalakshmi Varma and Robert H. Coker
and Gouri Ranganathan and Bounleut Phanavanh and Neda Rasouli and
Philip A. Kern},
title = {Adipose triglyceride lipase expression in human adipose tissue and
muscle. Role in insulin resistance and response to training and pioglitazone},
journal = {Metabolism},
year = {2011},
volume = {60},
pages = {1012 - 1020},
number = {7},
abstract = {Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte
and muscle triglyceride hydrolysis, and comparative gene identification–58
(CGI-58) is an essential cofactor. We studied the expression of ATGL
and CGI-58 in human adipose and muscle and examined correlations
with markers of muscle fatty acid oxidation. Nondiabetic volunteers
were studied. Subjects with impaired glucose tolerance were treated
with pioglitazone or metformin for 10 weeks. Subjects with normal
glucose tolerance underwent a 12-week training program. We examined
changes in ATGL and CGI-58 with obesity and insulin resistance, and
effects of exercise and pioglitazone. Adipose triglyceride lipase
messenger RNA (mRNA) expression showed no correlation with either
body mass index or insulin sensitivity index in either adipose or
muscle. However, adipose ATGL protein levels were inversely correlated
with body mass index (r = −0.64, P < .02) and positively correlated
with insulin sensitivity index (r = 0.67, P < .02). In muscle,
ATGL mRNA demonstrated a strong positive relationship with carnitine
palmitoyltransferase I mRNA (r = 0.82, P < .0001) and the adiponectin
receptors AdipoR1 mRNA (r = 0.71, P < .0001) and AdipoR2 mRNA
(r = 0.74, P < .0001). Muscle CGI-58 mRNA was inversely correlated
with intramyocellular triglyceride in both type 1 (r = −0.35, P
< .05) and type 2 (r = −0.40, P < .05) fibers. Exercise training
resulted in increased muscle ATGL, and pioglitazone increased adipose
ATGL by 31% (P < .05). Pioglitazone also increased ATGL in adipocytes.
Adipose ATGL protein is decreased with insulin resistance and obesity;
and muscle ATGL mRNA is associated with markers of fatty acid oxidation
in muscle, as is CGI-58. The regulation of ATGL and CGI-58 has important
implications for the control of lipotoxicity.},
doi = {10.1016/j.metabol.2010.10.005},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/pii/S0026049510003586}
}
@ARTICLE{Yap2009,
author = {Yap, Oi Wah Stephanie And Bhat, Ganapathy And Liu, Liang And Tollefsbol,
Trygve O.},
title = {Epigenetic Modifications of the Estrogen Receptor {beta} Gene in
Epithelial Ovarian Cancer Cells},
journal = {Anticancer Res},
year = {2009},
volume = {29},
pages = {139--144},
number = {1},
month = jan,
abstract = {Background: The mechanisms of estrogen insensitivity or estrogen resistance
in ovarian cancer cells are not known. Studies on regulation of the
estrogen receptor (ER) gene have suggested a role for epigenetics
in silencing ER expression. Materials and Methods: Cells from insensitive
ovarian cancer cells, SKOV3 and HEY, were cultured with and without
the DNA methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine
(AzaC) and the histone deacetylase (HDAC) inhibitor, trichostatin
(TSA). ER{beta} promoter methylation was examined using bisulfite
sequencing. RNA was collected for oligonucleotide array studies.
Results: Cell type-specific ER{beta} promoter methylation was found
as well as relative hypomethylation of the ER{beta} promoter in SKOV3
compared to HEY cells. Preferential demethylation of specific CpGs
by different treatments was found. AzaC and TSA resulted in significant
tumor growth inhibition and alterations in expression of numerous
genes. Conclusion: The ER{beta} promoter is differentially methylated
in ovarian cancer cells. Moreover, AzaC and TSA can inhibit ovarian
cancer cell growth.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/29/1/139}
}
@ARTICLE{Yardley2005,
author = {Yardley, Vanessa And Croft, Simon L. And De Doncker, Simonne And
Dujardin, Jean-claude And Koirala, Siddhartha And Rijal, Suman And
Miranda, Cesar And Llanos-cuentas, Alejandro And Chappuis, Francois},
title = {The Sensitivity Of Clinical Isolates Of Leishmania From Peru And
Nepal To Miltefosine},
journal = {Am J Trop Med Hyg},
year = {2005},
volume = {73},
pages = {272--275},
number = {2},
month = aug,
abstract = {Clinical isolates of Leishmania, from visceral leishmaniasis (VL)
cases in Nepal and from cutaneous leishmaniasis (CL) cases in Peru,
were cultured using polymerase chain reaction-restriction fragment
length polymorphism (PCR-RFLP) to type species and strain. Promastigotes
from 38 isolates, within eight passages from isolation, were used
to infect mouse peritoneal macrophage cultures in vitro, and the
amastigote sensitivity to miltefosine was determined. The concentration
required to kill 50% of intracellular amastigotes from Nepalese VL
isolates, all typed as Leishmania (L.) donovani (N = 24) from both
Sbv responders and nonresponders, ranged from 8.7 to 0.04 {micro}g/mL.
In contrast, the concentration required to kill 50% intracellular
amastigotes from isolates from Peru, typed as L.(V.) braziliensis
(N = 8), was > 30 to 8.4 {micro}g/mL, L.(V.) guyanensis (N = 2) >
30 to 1.9 {micro}g/mL, L.(L.) mexicana (N = 1) > 30 {micro}g/mL,
and L. (V.) lainsoni (N = 4) was 3.4 to 1.9 {micro}g/mL. This demonstrates
a notable difference in the intrinsic sensitivity of Leishmania species
to miltefosine in vitro. If this model can be correlated to therapeutic
outcome, it may have implications for the interpretation of clinical
trials.},
url = {http://www.ajtmh.org/cgi/content/abstract/73/2/272}
}
@ARTICLE{Yassour2009,
author = {Yassour, Moran and Kaplan, Tommy and Fraser, Hunter B. and Levin,
Joshua Z. and Pfiffner, Jenna and Adiconis, Xian and Schroth, Gary
and Luo, Shujun and Khrebtukova, Irina and Gnirke, Andreas and Nusbaum,
Chad and Thompson, Dawn-Anne and Friedman, Nir and Regev, Aviv},
title = {Ab initio construction of a eukaryotic transcriptome by massively
parallel mRNA sequencing},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {3264--3269},
number = {9},
month = mar,
abstract = {Defining the transcriptome, the repertoire of transcribed regions
encoded in the genome, is a challenging experimental task. Current
approaches, relying on sequencing of ESTs or cDNA libraries, are
expensive and labor-intensive. Here, we present a general approach
for ab initio discovery of the complete transcriptome of the budding
yeast, based only on the unannotated genome sequence and millions
of short reads from a single massively parallel sequencing run. Using
novel algorithms, we automatically construct a highly accurate transcript
catalog. Our approach automatically and fully defines 86% of the
genes expressed under the given conditions, and discovers 160 previously
undescribed transcription units of 250 bp or longer. It correctly
demarcates the 5' and 3' UTR boundaries of 86 and 77% of expressed
genes, respectively. The method further identifies 83% of known splice
junctions in expressed genes, and discovers 25 previously uncharacterized
introns, including 2 cases of condition-dependent intron retention.
Our framework is applicable to poorly understood organisms, and can
lead to greater understanding of the transcribed elements in an explored
genome.},
url = {http://www.pnas.org/cgi/content/abstract/106/9/3264}
}
@ARTICLE{Yassour2010,
author = {Yassour, Moran and Pfiffner, Jenna and Levin, Joshua and Adiconis,
Xian and Gnirke, Andreas and Nusbaum, Chad and Thompson, Dawn-Anne
and Friedman, Nir and Regev, Aviv},
title = {Strand-specific RNA sequencing reveals extensive regulated long antisense
transcripts that are conserved across yeast species},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R87},
number = {8},
abstract = {BACKGROUND:Recent studies in budding yeast have shown that antisense
transcription occurs at many loci. However, the functional role of
antisense transcripts has been demonstrated only in a few cases and
it has been suggested that most antisense transcripts may result
from promiscuous bi-directional transcription in a dense genome.RESULTS:Here,
we use strand-specific RNA sequencing to study anti-sense transcription
in Saccharomyces cerevisiae. We detect 1,103 putative antisense transcripts
expressed in mid-log phase growth, ranging from 39 short transcripts
covering only the 3' UTR of sense genes to 145 long transcripts covering
the entire sense open reading frame. Many of these antisense transcripts
overlap sense genes that are repressed in mid-log phase and are important
in stationary phase, stress response, or meiosis. We validate the
differential regulation of 67 antisense transcripts and their sense
targets in relevant conditions, including nutrient limitation and
environmental stresses. Moreover, we show that several antisense
transcripts and, in some cases, their differential expression have
been conserved across five species of yeast spanning 150 million
years of evolution. Divergence in the regulation of antisense transcripts
to two respiratory genes coincides with the evolution of respiro-fermentation.CONCLUSIONS:Our
work provides support for a global and conserved role for antisense
transcription in yeast gene regulation.},
doi = {10.1186/gb-2010-11-8-r87},
issn = {1465-6906},
pubmedid = {20796282},
url = {http://genomebiology.com/2010/11/8/R87}
}
@ARTICLE{Yasuda2009,
author = {Yasuda, Koji and Dawson, Harry D. and Wasmuth, Elizabeth V. and Roneker,
Carol A. and Chen, Celine and Urban, Joseph F. and Welch, Ross M.
and Miller, Dennis D. and Lei, Xin Gen},
title = {Supplemental Dietary Inulin Influences Expression of Iron and Inflammation
Related Genes in Young Pigs},
journal = {J. Nutr.},
year = {2009},
volume = {139},
pages = {2018--2023},
number = {11},
month = nov,
abstract = {We have previously shown improved hemoglobin (Hb) repletion efficiency
by supplementing a 50:50 mixture of short (P95) and long-chain (HP)
inulin (Synergy 1, BENEO-Orafti) into a corn-soybean meal-basal diet
(BD) for young pigs. In this study, weanling pigs (5 or 6 wk old)
were fed the BD or the BD + 4% of P95, HP, or Synergy 1 (50:50 mixtures
of HP and P95) for 5-7 wk. Blood Hb concentrations of pigs were measured
weekly and digesta samples were collected at the end of the trial.
In a replicate experiment, total RNA was isolated from the liver
and mucosa of duodenum, ileum, cecum, and colon of all pigs at the
end of the trial. Relative mRNA expression of 27 genes, including
iron and inflammation-related genes, was quantified using real-time
quantitative-PCR. Although all 3 types of inulin resulted in similar
improvements (P < 0.05) in blood Hb concentration and liver ferritin
protein amount, neither type of inulin was detectable in the digesta
of cecum or colon. Supplemental inulin enhanced the expression of
iron-storing protein genes but decreased that of inflammation-related
genes. Such effects were more pronounced (P < 0.05) in the mucosa
of the lower than the upper gut and were seen on 7 genes in liver.
In conclusion, all 3 types of inulin shared similar efficacy and
possibly similar modes of action in improving dietary iron utilization
by young pigs. Suppressing inflammation-induced genes that can negatively
influence iron metabolism might help explain the benefit of inulin.},
url = {http://jn.nutrition.org/cgi/content/abstract/139/11/2018}
}
@ARTICLE{Yates2009,
author = {Yates, Melinda S. and Tran, Quynh T. and Dolan, Patrick M. and Osburn,
William O. and Shin, Soona and McCulloch, Colin C. and Silkworth,
Jay B. and Taguchi, Keiko and Yamamoto, Masayuki and Williams, Charlotte
R. and Liby, Karen T. and Sporn, Michael B. and Sutter, Thomas R.
and Kensler, Thomas W.},
title = {Genetic versus chemoprotective activation of Nrf2 signaling: overlapping
yet distinct gene expression profiles between Keap1 knockout and
triterpenoid-treated mice},
journal = {Carcinogenesis},
year = {2009},
volume = {30},
pages = {1024--1031},
number = {6},
month = jun,
abstract = {Loss of NF-E2-related factor 2 (Nrf2) signaling increases susceptibility
to acute toxicity, inflammation and carcinogenesis in mice due to
the inability to mount adaptive responses. In contrast, disruption
of Keap1 (a cytoplasmic modifier of Nrf2 turnover) protects against
these stresses in mice, although inactivating mutations in Keap1
have been identified recently in some human cancers. Global characterization
of Nrf2 activation is important to exploit this pathway for chemoprevention
in healthy, yet at-risk individuals and also to elucidate the consequences
of hijacking the pathway in Keap1-mutant human cancers. Liver-targeted
conditional Keap1-null, Albumin-Cre:Keap1(flox/-) (CKO) mice provide
a model of genetic activation of Nrf2 signaling. By coupling global
gene expression analysis of CKO mice with analysis of pharmacologic
activation using the synthetic oleanane triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole
(CDDO-Im), we are able to gain insight into pathways affected by
Nrf2 activation. CDDO-Im is an extremely potent activator of Nrf2
signaling. CKO mice were used to identify genes modulated by genetic
activation of Nrf2 signaling. The CKO response was compared with
hepatic global gene expression changes in wild-type mice treated
with CDDO-Im at a maximal Nrf2 activating dose. The results show
that genetic and pharmacologic activation of Nrf2 signaling modulates
pathways beyond detoxication and cytoprotection, with the largest
cluster of genes associated with lipid metabolism. Genetic activation
of Nrf2 results in much larger numbers of detoxication and lipid
metabolism gene changes. Additionally, analysis of pharmacologic
activation suggests that Nrf2 is the primary mediator of CDDO-Im
activity, though other cell-signaling targets are also modulated
following an oral dose of 30 {micro}mol/kg.},
url = {http://carcin.oxfordjournals.org/cgi/content/abstract/30/6/1024}
}
@ARTICLE{Yates2007,
author = {Yates, Stephen F. and Paterson, Alison M. and Nolan, Kathleen F.
and Cobbold, Stephen P. and Saunders, Nigel J. and Waldmann, Herman
and Fairchild, Paul J.},
title = {Induction of Regulatory T Cells and Dominant Tolerance by Dendritic
Cells Incapable of Full Activation},
journal = {J. Immunol.},
year = {2007},
volume = {179},
pages = {967--976},
number = {2},
month = jul,
abstract = {Transplants tolerated through a process known as infectious tolerance
evoke continuous recruitment of regulatory T (Treg) cells that are
necessary to maintain the unresponsive state. This state is maintained
long-term and requires continuous Ag exposure. It is not known, however,
whether infectious tolerance operates through sustained recruitment
of pre-existing regulatory cells, induction of regulatory cells,
or both. Using mice deficient in natural Treg cells, we show here
that quiescent donor dendritic cells (DC) laden with histocompatibility
Ag can induce Treg cells de novo that mediate transplantation tolerance.
In contrast, fully activated DC fail to do so. These findings suggest
that DC incapable of delivering full activation signals to naive
T cells may favor their polarization toward a regulatory phenotype.
Furthermore, they suggest a role for quiescent endogenous DC in the
maintenance of the tolerant state.},
url = {http://www.jimmunol.org/cgi/content/abstract/179/2/967}
}
@ARTICLE{Yatsushiro2011,
author = {Yatsushiro, Shouki and Kataoka, Masatoshi},
title = {Application of microchip electrophoresis for clinical tests},
journal = {Electrical Engineering in Japan},
year = {2011},
volume = {177},
pages = {19--25},
number = {1},
abstract = {Microchip electrophoresis has recently attracted much attention in
the field of nuclear acid analysis due to its high efficiency, ease
of operation, low consumption of samples and reagents, and relatively
low costs. In addition, the analysis has expanded to analytical fields,
including the analysis not only of DNA but also of RNA, proteins,
sugar chains, cellular functions, etc. In this paper we describe
the creation of high-performance monitoring systems for human blood
glucose levels and α-amylase activity in human plasma using microchip
electrophoresis. © 2011 Wiley Periodicals, Inc. Electr Eng Jpn,
177(1): 19–25, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com).
DOI 10.1002/eej.21158},
doi = {10.1002/eej.21158},
issn = {1520-6416},
keywords = {microchip electrophoresis, nucleic acid, blood sugar, α-amylase,
biomarker},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/eej.21158}
}
@ARTICLE{Yau2008,
author = {Yau, Christina and Benz, Christopher},
title = {Genes responsive to both oxidant stress and loss of estrogen receptor
function identify a poor prognosis group of estrogen receptor positive
primary breast cancers},
journal = {Breast Cancer Research},
year = {2008},
volume = {10},
pages = {R61},
number = {4},
note = {See related editorial by Neven et al., http://breast-cancer-research.com/content/10/5/109},
abstract = {INTRODUCTION:Oxidative stress can modify estrogen receptor (ER) structure
and function, including induction of progesterone receptor (PR),
altering the biology and clinical behavior of endocrine responsive
(ER-positive) breast cancer.METHODS:To investigate the impact of
oxidative stress on estrogen/ER-regulated gene expression, RNA was
extracted from ER-positive/PR-positive MCF7 breast cancer cells after
72 hours of estrogen deprivation, small-interfering RNA knockdown
of ER-a, short-term (8 hours) exposure to various oxidant stresses
(diamide, hydrogen peroxide, and menadione), or simultaneous ER-a
knockdown and oxidant stress. RNA samples were analyzed by high-throughput
expression microarray (Affymetrix), and significance analysis of
microarrays was used to define gene signatures responsive to estrogen/ER
regulation and oxidative stress. To explore the association of these
signatures with breast cancer biology, microarray data were analyzed
from 394 ER-positive primary human breast cancers pooled from three
independent studies. In particular, an oxidant-sensitive estrogen/ER-responsive
gene signature (Ox-E/ER) was correlated with breast cancer clinical
parameters and disease-specific patient survival (DSS).RESULTS:From
891 estrogen/ER-regulated probes, a core set of 75 probes (62 unique
genes) responsive to all three oxidants were selected (Ox-E/ER signature).
Ingenuity pathway analysis of this signature highlighted networks
involved in development, cancer, and cell motility, with intersecting
nodes at growth factors (platelet-derived growth factor-BB, transforming
growth factor-ß), a proinflammatory cytokine (tumor necrosis factor),
and matrix metalloproteinase-2. Evaluation of the 394 ER-positive
primary breast cancers demonstrated that Ox-E/ER index values correlated
negatively with PR mRNA levels (rp = -0.2; P = 0.00011) and positively
with tumor grade (rp = 0.2; P = 9.741 × e-5), and were significantly
higher in ER-positive/PR-negative versus ER-positive/PR-positive
breast cancers (t-test, P = 0.0008). Regardless of PR status, the
Ox-E/ER index associated with reduced DSS (n = 201; univariate Cox,
P = 0.078) and, using the optimized cut-point, separated ER-positive
cases into two significantly different DSS groups (log rank, P =
0.0009).CONCLUSION:An oxidant-sensitive subset of estrogen/ER-responsive
breast cancer genes linked to cell growth and invasion pathways was
identified and associated with loss of PR and earlier disease-specific
mortality, suggesting that oxidative stress contributes to the development
of an aggressive subset of primary ER-positive breast cancers.},
doi = {10.1186/bcr2120},
issn = {1465-5411},
pubmedid = {18631401},
url = {http://breast-cancer-research.com/content/10/4/R61}
}
@ARTICLE{Yauk2004,
author = {Yauk, Carole L. and Berndt, M. Lynn and Williams, Andrew and Douglas,
George R.},
title = {Comprehensive comparison of six microarray technologies},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {e124--},
number = {15},
month = aug,
abstract = {Microarray technology is extensively used in biological research.
The applied technologies vary greatly between laboratories, and outstanding
questions remain regarding the degree of correlation among approaches.
Recently, there has been a drive toward ensuring high-quality microarray
data by the implementation of MIAME (Minimal Information About a
Microarray Experiment) guidelines and an emphasis on ensuring public-availability
to all datasets. However, despite its current widespread use and
availability, very little is known about the extent to which application
of the different technologies influences the outcome of transcriptional
profiles and differential expression. The results among the handful
of published studies are conflicting. Here, we present a comprehensive
evaluation encompassing different reporter systems (short oligonucleotides,
long oligonucleotides and cDNAs), labelling techniques and hybridization
protocols. We used four oligonucleotide and two cDNA platforms to
compare gene expression between two sample types. We determined the
overall consistency (reproducibility) within each platform, and correlation
among replicates within and between technologies. We find that the
top performing platforms show low levels of technical variability
that result in an increased ability to detect differential expression.
Most importantly, we show the top four platforms are highly correlated
with biological, rather than technological, differences accounting
for the majority of variation in the data.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/15/e124}
}
@ARTICLE{Yauk2011,
author = {Carole Lyn Yauk and Kelly Jackson and Morie Malowany and Andrew Williams},
title = {Lack of change in microRNA expression in adult mouse liver following
treatment with benzo(a)pyrene despite robust mRNA transcriptional
response},
journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis},
year = {2011},
volume = {722},
pages = {131 - 139},
number = {2},
note = {Omics - Application and Impacts on Genotoxicity Assessment},
abstract = {Benzo(a)pyrene (BaP) is a mutagenic and carcinogenic environmental
contaminant. Metabolic activation of BaP is required for it to exert
its mutagenic effects. Metabolism occurs via BaP interaction with
the aryl hydrocarbon receptor (AHR) resulting in induction of phase
1 enzymes. Exposure to BaP is expected to cause differential regulation
of AHR-responsive genes as well as pathways responding to DNA damage
induced by its metabolites. MicroRNAs (miRNAs) are short non-coding
molecules that control mRNA levels and protein translation. MiRNA
regulation may also be affected by chemical insult. Here we investigate
the correlation between hepatic mRNA and miRNA response to BaP in
vivo. Mature male mice were orally exposed to 3 daily doses of 150 mg/kg
BaP. DNA microarrays were used to profile gene and miRNA expression
in the liver 4 and 24 h following the final dose. Despite widespread
changes in gene expression (>400 genes) in pathways consistent
with the known effects of BaP, we found no changes in miRNA. This
was confirmed on two microarray platforms and by qRT-PCR. Analysis
of positive controls (2 distinct reference pools) indicated that
the Agilent technology could identify differences in miRNA. The effects
of sample storage at −80 °C were also compared. We found
little effect of prolonged freezing on the technical correlation
between samples or on differential expression. Our results are consistent
with the lack of response of miRNA in rodent liver to dioxin, another
potent AHR-agonist. We conclude that hepatic miRNA in vivo is not
directly responsive to BaP exposure.},
doi = {10.1016/j.mrgentox.2010.02.012},
issn = {1383-5718},
keywords = {Benzo(a)pyrene},
url = {http://www.sciencedirect.com/science/article/pii/S1383571810000768}
}
@ARTICLE{Ye2007,
author = {Ye, Ping and Mariniello, Barbara and Mantero, Franco and Shibata,
Hirotaka and Rainey, William E},
title = {G-protein-coupled receptors in aldosterone-producing adenomas: a
potential cause of hyperaldosteronism},
journal = {J. Endocrinol.},
year = {2007},
volume = {195},
pages = {39--48},
number = {1},
month = oct,
abstract = {The source of aldosterone in 30-40% of patients with primary hyperaldosteronism
(PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms
causing elevated aldosterone production in APA are unknown. Herein,
we examined the expression of G-protein-coupled receptors (GPCRs)
in APA and demonstrated that when compared with normal adrenals,
there is a general elevation of certain GPCR in many APA and/or ectopic
expression of GPCR in others. RNA samples from normal adrenals (n
= 5), APAs (n = 10), and cortisol-producing adenomas (CPAs; n = 13)
were used on 15 genomic expression arrays, each of which included
223 GPCR transcripts presented in at least 1 out of 15 of the independent
microarrays. The array results were confirmed using real-time RT-PCR
(qPCR). Four GPCR transcripts exhibited a statistically significant
increase that was greater than threefold when compared with normal
adrenals, suggesting a general increase in expression when compared
with normal adrenal glands. Four GPCR transcripts exhibited a > 15-fold
increase of expression in one or more of the APA samples when compared
with normal adrenals. qPCR analysis confirmed array data and found
the receptors with the highest fold increase in APA expression to
be LH receptor, serotonin receptor 4, GnRH receptor, glutamate receptor
metabotropic 3, endothelin receptor type B-like protein, and ACTH
receptor. There are also sporadic increased expressions of these
genes in the CPAs. Together, these findings suggest a potential role
of altered GPCR expression in many cases of PA and provide candidate
GPCR for further study.},
url = {http://joe.endocrinology-journals.org/cgi/content/abstract/195/1/39}
}
@ARTICLE{Ye2009,
author = {Ye, Ping and Nakamura, Yashuhiro and Lalli, Enzo and Rainey, William
E.},
title = {Differential Effects of High and Low Steroidogenic Factor-1 Expression
on CYP11B2 Expression and Aldosterone Production in Adrenocortical
Cells},
journal = {Endocrinology},
year = {2009},
volume = {150},
pages = {1303--1309},
number = {3},
month = mar,
abstract = {Steroidogenic factor-1 (SF-1/Ad4BP/NR5A1) plays a major role in regulating
steroidogenic enzymes. We have previously shown that SF-1 inhibits
aldosterone synthase (CYP11B2) reporter gene activity. Herein, we
used the H295R/TR/SF-1 adrenal cells that increase SF-1 in a doxycycline-dependent
fashion. Cells were incubated with or without doxycycline to induce
SF-1 and then treated with angiotensin II (Ang II). Aldosterone was
measured by immunoassay. SF-1 mRNA was silenced by small interfering
RNA (siRNA) by Nucleofector technology. mRNA levels were measured
by real-time RT-PCR. Ang II treatment without doxycycline increased
aldosterone production by 11.3-fold and CYP11B2 mRNA by 116-fold.
Doxycycline treatment increased SF-1 mRNA levels by 3.7-fold and
inhibited Ang II-induced aldosterone by 84%. Doxycycline treatment
inhibited Ang II-stimulated CYP11B2 mRNA levels by 86%. Doxycycline
decreased basal CYP11B2 promoter activity by 68%. Doxycycline inhibited
Ang II stimulation by 85%. Ang II increased CYP21 mRNA expression
by 4.6-fold, whereas doxycycline inhibited induction by 69%. In contrast,
doxycycline treatment increased CYP11B1 mRNA by 1.7-fold in basal
cells and increased Ang II induction by 3.6-fold. SF-1-specific siRNA
significantly reduced SF-1 mRNA expression as compared with cells
treated with control siRNA. SF-1 siRNA reversed doxycycline stimulation
of CYP B1 and its inhibition of CYP11B2. However, in H295R/TR/SF-1
cells without doxycycline treatment, both CYP11B1 and CYP11B2 mRNAs
were significantly decreased, suggesting that both enzymes require
a minimal level of SF-1 for basal expression. In summary, SF-1 overexpression
dramatically inhibited CYP11B2 expression and decreased aldosterone
production. The opposing effects of SF-1 on CYP11B1 and CYP11B2 suggest
that the regulation of SF-1 activity may play a role that determines
the relative ability to produce mineralocorticoid and glucocorticoid.},
url = {http://endo.endojournals.org/cgi/content/abstract/150/3/1303}
}
@ARTICLE{Yea2007,
author = {Yea, C. and Adachi, D. and Johnson, G. and Nagy, E. and Gharabaghi,
F. and Petric, M. and Richardson, S.E. and Tellier, R.},
title = {Design of a single tube RT-PCR assay for the diagnosis of human infection
with highly pathogenic influenza A(H5) viruses},
journal = {Journal of Virological Methods},
year = {2007},
volume = {139},
pages = {220--226},
number = {2},
month = feb,
abstract = {Concerns about emergence of a pandemic strain of influenza have been
increasing. The strains of highly pathogenic influenza A(H5N1) currently
circulating are considered among the most plausible candidates for
giving rise to a pandemic strain. In this study the design and development
of a RT-PCR assay specific for these highly pathogenic influenza
A(H5) strains is presented. This is achieved in part by the design
of a primer targeting the coding region for the protease cleavage
site of the hemagglutinin, and another primer derived from a pan-hemagglutinin
RT-PCR assay also presented in this study. It is shown that the HPAI
A(H5) specific assay amplifies only the nucleic acids of higly pathogenic
A(H5), with a high sensitivity.},
issn = {0166-0934},
keywords = {Influenza A virus, Pandemic, Highly pathogenic influenza A(H5N1),
RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6T96-4MD460B-1/2/e7198e0ed37a0ee6aa2a1955efa8b5aa}
}
@ARTICLE{Yea2010,
author = {Yea, C. and Petric, M. and Pasick, J. and Tellier, R.},
title = {A new RT-PCR assay specific for influenza A(H2), multiplexed with
an assay specific for HPAI A(H5N1)},
journal = {Molecular and Cellular Probes},
year = {2010},
volume = {24},
pages = {364--369},
number = {6},
month = dec,
abstract = {Worldwide efforts are ongoing to improve influenza pandemic preparedness,
including from the perspective of the clinical virology laboratory.
In particular, much work has been devoted to the development of diagnostic
assays targeted at the Highly Pathogenic Avian Influenza (HPAI) A(H5N1);
much less efforts have been devoted to the A(H2) subtype. Yet, A(H2)
subtype has a proven capacity to cause pandemics and is among the
subtypes prioritized for surveillance and control. Although the human
A(H2N2) virus that caused the pandemic of 1957 no longer circulates,
many related avian A(H2) viruses circulate in avian population and
could conceivably adapt to infect humans and cause a new pandemic.
In this study the design and development of an RT-PCR assay specific
for A(H2) subtype is presented. It is shown that the assay is highly
sensitive and specific, able to detect human and avian A(H2) viruses,
and can be incorporated into a multiplex assay with another previously
described assay for HPAI A(H5N1).},
issn = {0890-8508},
keywords = {Influenza A virus, Pandemic, Influenza A(H2), RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6WNC-50T9WW7-1/2/9c74c571a1d341c96f5a2bc0a63a1272}
}
@ARTICLE{Yeh2008,
author = {Yeh, Ching-Ju and Lin, Ping-Yuan and Liao, Ming-Huei and Liu, Hung-Jen
and Lee, Jeng-Woei and Chiu, Shu-Jun and Hsu, Hsue-Yin and Shih,
Wen-Ling},
title = {TNF-[alpha] mediates pseudorabies virus-induced apoptosis via the
activation of p38 MAPK and JNK/SAPK signaling},
journal = {Virology},
year = {2008},
volume = {381},
pages = {55--66},
number = {1},
month = nov,
abstract = {PRV infection causes apoptosis in vitro and in vivo. However, the
significance of PRV-induced apoptosis and its signaling pathways
is still unknown. This work investigates the role of MAPK pathways
in mediating PRV-induced apoptosis. Flow cytometry, apoptosis ELISA
and western blotting using antibodies against cleaved caspase-3,
-6 and PARP demonstrated that PRV induces apoptosis in a time- and
dose-dependent manner. p38 and JNK/SAPK inhibitors significantly
protected cells from PRV-induced apoptosis. Inhibitor treatment did
not affect Us3a gene transcription and progeny virus production.
Western blotting revealed that PRV activates p38 and JNK/SAPK signaling.
Inhibition of NF-[kappa]B had no effect on PRV-mediated apoptosis.
Non-replicative PRV failed to activate p38 and JNK/SAPK or induce
apoptosis. PRV infection increases TNF-[alpha] transcription, translation
and secretion, as well as TNF-[alpha] receptor expression. Inhibition
of p38 and JNK/SAPK reduced PRV-induced TNF-[alpha] up-regulation.
Neutralization assay confirmed that TNF-[alpha] is a key mediator
involved in PRV-induced apoptosis.},
issn = {0042-6822},
keywords = {Pseudorabies virus, p38, JNK/SAPK, SB203580, SP600125, NF-[kappa]B,
Apoptosis, TNF-[alpha]},
url = {http://www.sciencedirect.com/science/article/B6WXR-4TG28VR-6/2/380c5dad2867a24772ccae0c8c96ae16}
}
@ARTICLE{Yeh2010,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Sequence analysis, characterization and tissue distribution of channel
catfish (Ictalurus punctatus Rafinesque, 1818) myeloperoxidase cDNA},
journal = {Fish \& Shellfish Immunology},
year = {2010},
volume = {28},
pages = {504--509},
number = {3},
month = mar,
abstract = {Myeloperoxidase (EC 1.11.1.7), a heme-containing lysosomal glycoprotein,
is found predominantly in azurophilic granules of neutrophils. This
enzyme upon activation catalyzes hydrogen peroxide in the presence
of various halide ions to form hypohalous acids. Subsequently, these
reagents are able to kill the invading microorganisms. In this study,
we report the identification, characterization and expression analysis
of the channel catfish myeloperoxidase transcript. The full-length
nucleotide sequence of channel catfish myeloperoxidase cDNA had 3157
nucleotides, including an open reading frame, which appears to encode
a putative peptide of 771 amino acid residues with a calculated molecular
mass of 87.14 kDa. By comparison with the human counterpart, the
channel catfish myeloperoxidase peptide can be divided into domains
and has conservative features, including peroxidase catalytic sites,
covalent linkage sites for the heme group and all cysteine residues.
The channel catfish myeloperoxidase transcript was detected by RT-PCR
in anterior kidneys, where the major leukocyte population is neutrophil
precursors. Reagent development and the role of this enzyme in Edwardsiella
ictaluri infection are under investigation.},
issn = {1050-4648},
keywords = {Channel catfish, Ictalurus punctatus, Myeloperoxidase, MPO, Edwardsiella
ictaluri},
url = {http://www.sciencedirect.com/science/article/B6WFN-4Y0KWGM-1/2/00892249d2de8018daeacba112b47eda}
}
@ARTICLE{Yeh2010a,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Sequence analysis, characterization and mRNA distribution of channel
catfish (Ictalurus punctatus Rafinesque, 1818) chemokine (C-X-C motif)
receptor 4 (CXCR4) cDNA},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {134},
pages = {289--295},
number = {3-4},
month = apr,
abstract = {Chemokine receptor CXCR4, a member of the G protein-coupled receptor
superfamily, binds selectively CXCL12. This protein plays many important
roles in immunological as well as pathophysiological functions. In
this study, we identified and characterized the channel catfish CXCR4
transcript. The full-length nucleic acid sequence of channel catfish
CXCR4 cDNA comprised of 1994 nucleotides, including an open reading
frame, which appears to encode a putative peptide of 357 amino acid
residues with a calculated molecular mass of 40.1 kDa. By comparison
with the human counterpart, the channel catfish CXCR4 peptide can
be divided into domains, including seven transmembrane domains, four
cytoplasmic domains, and four extracellular domains. The CXCR4 transcript
was detected in spleen, anterior kidney, liver, intestine, skin and
gill of all catfish examined in this study. Because four CXCL of
channel catfish have been identified, the result provides valuable
information for further exploring the channel catfish chemokine signalling
pathways and their roles in immune responses to infection.},
issn = {0165-2427},
keywords = {CX chemokine receptor 4, CXCR4, Channel catfish, Ictalurus punctatus},
url = {http://www.sciencedirect.com/science/article/B6TD5-4XC57CY-2/2/15315a9e1abbc57c7bec56eaa408a0e3}
}
@ARTICLE{Yeh2010b,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Identification, phylogenetic relationships, characterization and
gene expression patterns of six different annexins of channel catfish
(Ictalurus punctatus Rafinesque, 1818)},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {136},
pages = {176--183},
number = {1-2},
month = jul,
abstract = {Annexins are Ca2+-dependent phospholipid-binding proteins. They are
ubiquitous in living organisms and are involved in many cellular
processes. In the course of studying Edwardsiella ictaluri pathogenesis
in channel catfish, we identified that six annexin expressed sequence
tags (A1, A2, A4, A5, A6 and A11) were up-regulated at the early
stage of infection. In this study, we cloned and characterized these
transcripts. The full-length nucleic acid sequences of channel catfish
annexins ranges from 1231 (annexin A1) to 2476 (annexin A6). Each
transcript has one open reading, which appears to encode peptides
ranges from 317 to 662 amino acid residues with the calculated molecular
masses from 35.0 (annexin A5) to 74.5 kDa (annexin A6). Phylogenetic
and sequence analyses demonstrate that each channel catfish annexin
had a diversified amino terminus, and had four structurally conserved
70-amino acid repeats. In addition, several important features for
annexin functions were conserved in channel catfish. For expression
profile, channel catfish annexin A1, A4 and A6 transcripts were detected
in spleen, anterior kidney, liver, intestine, skin and gill of fish
examined. However, annexin A2, A5 and A11 cDNAs were variously detected
in tissues of fish sampled. This result provides important information
for further elucidating channel catfish annexin functions in vivo.},
issn = {0165-2427},
keywords = {Annexins, Channel catfish, Ictalurus punctatus, Edwardsiella ictaluri},
url = {http://www.sciencedirect.com/science/article/B6TD5-4YG1KTH-2/2/2ba3582e2b7cd6257f852f9484b835be}
}
@ARTICLE{Yeh2010c,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Channel catfish (Ictalurus punctatus Rafinesque, 1818) tetraspanin
membrane protein family: Identification, characterization and expression
analysis of CD63 cDNA},
journal = {Veterinary Immunology and Immunopathology},
year = {2010},
volume = {133},
pages = {302--308},
number = {2-4},
month = feb,
abstract = {CD63, known as lysosome associated membrane protein 3 (LAMP-3), is
a member of the tetraspanin integral membrane protein family. This
protein plays many important roles in immuno-physiological functions.
In this communication, we report the identification, characterization,
and expression analysis of the channel catfish CD63 transcript. The
complete nucleic acid sequence of channel catfish CD63 cDNA was comprised
of 1159 nucleotides, including an open reading frame, which appears
to encode a putative peptide of 237-amino-acid residues. Like other
tetraspanin proteins, the channel catfish CD63 peptide can be divided
into domains, including four transmembrane domains, three intracellular
domains, and one of each small and large extracellular loops. The
channel catfish CD63 peptide shares 52-55% identity among fish counterparts,
but only 43-46% identity among mammalian counterparts. The characteristic
Cys-Cys-Gly motif and four Cys residues in the large extracellular
loop were conserved. The channel catfish CD63 transcript was detected
by RT-PCR in spleen, anterior kidney, liver, intestine, skin and
gill. This result provides important information for further elucidating
CD63 functions in channel catfish.},
issn = {0165-2427},
keywords = {CD63, Tetraspanin protein, Lysosome associated membrane protein 3,
LAMP-3, Channel catfish, Ictalurus punctatus},
url = {http://www.sciencedirect.com/science/article/B6TD5-4X0F3P6-7/2/1fa2012164a2c69c13399eb072490fa6}
}
@ARTICLE{Yeh2008a,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Channel catfish, Ictalurus punctatus, cyclophilin A and B cDNA characterization
and expression analysis},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {121},
pages = {370--377},
number = {3-4},
month = feb,
abstract = {The preliminary observation of up-regulation of cyclophilin transcripts
during Edwardsiella ictaluri infection prompted us to speculate on
the potential importance of cyclophilins in the early stage of infection.
To provide a framework for answering these questions, two cyclophilin
cDNA of channel catfish, Ictalurus punctatus, were identified, sequenced
and characterized. The complete nucleotide sequences of cyclophilin
A and cyclophilin B cDNA consisted of 1170 and 996 bases, respectively.
Analyses of the sequences revealed each had one open reading frame
potentially encoding 164 amino acids with calculated molecular mass
of 17,450 Da and 216 amino acids with calculated molecular mass of
23,852 Da for cyclophilin A and cyclophilin B, respectively. The
degrees of conservation of channel catfish cyclophilin A and cyclophilin
B amino acid sequences to counterparts of other species ranged from
74 to 84% and 80 to 92%, respectively. Both cyclophilin A and cyclophilin
B transcripts were constitutively expressed in all tissues of channel
catfish examined in this study. These results provide valuable information
not only for further exploring the roles of cyclophilins in fish
immune responses to infection, but also for production of polyclonal/monoclonal
antibodies for channel catfish cyclophilins.},
issn = {0165-2427},
keywords = {Cyclophilin, Peptidyl-prolyl isomerase, Channel catfish, Ictalurus
punctatus},
url = {http://www.sciencedirect.com/science/article/B6TD5-4PT7WW0-H/2/b8719b7bd31673e3e90c14e1735887db}
}
@ARTICLE{Yeh2008b,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Molecular cloning, sequencing and characterization of channel catfish
(Ictalurus punctatus, Rafinesque 1818) cathepsin S gene},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {126},
pages = {382--387},
number = {3-4},
month = dec,
abstract = {Cathepsin S is a lysosomal cysteine endopeptidase of the papain family.
Our preliminary results showed the up-regulation of cathepsin S (CTSS)
transcript during the early stage of Edwardsiella ictaluri infection,
leading us to speculate that CTSS may play a role in infection. In
this report, we identified, sequenced and characterized the channel
catfish CTSS cDNA. Total RNA from tissues was isolated and cDNA libraries
were constructed by the rapid amplification cDNA end (RACE) method.
The gene-specific primers in conjunction with the RACE primers were
used to PCR amplify 5'- and 3'-ends of the CTSS transcript. The complete
channel catfish CTSS cDNA comprised 1530 nucleotides including a
96-nucleotide 5'-untranslated region (UTR), a 990-nucleotide open
reading frame and a 444-nucleotide 3'-UTR. The open reading frame
appears to encode a protein of 329 amino-acid residues with calculated
molecular mass of 36.7 kDa and pIof 5.96. The degree of conservation
of the channel catfish CTSS amino-acid sequence in comparison to
other species ranged from 56.6 to 68.5%. These results provide important
information for further exploring the roles of channel catfish CTSS
in antigen processing.},
issn = {0165-2427},
keywords = {Cathepsin S, Channel catfish, Ictalurus punctatus, Cysteine proteinase,
CTSS},
url = {http://www.sciencedirect.com/science/article/B6TD5-4T8SKWY-3/2/3ff92e2bc285d3bce53a81e3e7178cb8}
}
@ARTICLE{Yeh2007,
author = {Yeh, Hung-Yueh and Klesius, Phillip H.},
title = {Molecular cloning and expression of channel catfish, Ictalurus punctatus,
complement membrane attack complex inhibitor CD59},
journal = {Veterinary Immunology and Immunopathology},
year = {2007},
volume = {120},
pages = {246--253},
number = {3-4},
month = dec,
abstract = {The channel catfish, Ictalurus punctatus, complement membrane attack
complex inhibitor CD59 gene was cloned and analyzed. Total RNA from
tissues was isolated and cDNA libraries were constructed by the rapid
amplification cDNA end (RACE) method. The gene-specific primers in
conjunction with the RACE primers were used to PCR amplify 5'- and
3'-ends of the CD59 transcript. The complete channel catfish CD59
cDNA comprised 1109 bp including a 132-bp 5'-untranslated, a 360-bp
open reading frame, and a 617-bp 3'-untranslated region. The open
reading frame encodes a putative protein of 119-amino acid residues
with calculated molecular mass (without potential glycosylation)
of 13.2 kDa. However, the CD59 protein has a potential N-glycosylation
site at the Asn35 residue. The degree of conservation of the channel
catfish amino acid sequence to mammalian counterparts is 24-32%,
while to those of other fish species is 44-54%. One remarkable feature
is that the number and position of cysteine residues were conserved
in the mature protein among species examined, suggesting that although
the primary amino acid sequences are divergent, the three-dimensional
structure of CD59 via disulfide linkages may be conserved through
the evolutionary process. The putative protein could be further divided
into three domains: a 21-amino acid signal peptide at the N-terminus,
a 72-amino acid mature protein, and a 26-amino acid glycosylphosphatidylinositol
(GPI) anchoring signal peptide at the carboxyl terminus. CD59 was
expressed in all channel catfish tissues studied, suggesting that
like mammals, channel catfish CD59 is constitutively expressed.},
issn = {0165-2427},
keywords = {CD59, Channel catfish, Ictalurus punctatus, Complement membrane attack
complex inhibitor},
url = {http://www.sciencedirect.com/science/article/B6TD5-4PB6VRS-1/2/44f3449010628054e1cfe94a3f1573bf}
}
@ARTICLE{Yeh2009,
author = {Yeh, Yung-Hsin and Burstein, Brett and Qi, Xiao Yan and Sakabe, Masao
and Chartier, Denis and Comtois, Philippe and Wang, Zhiguo and Kuo,
Chi-Tai and Nattel, Stanley},
title = {Funny Current Downregulation and Sinus Node Dysfunction Associated
With Atrial Tachyarrhythmia: A Molecular Basis for Tachycardia-Bradycardia
Syndrome},
journal = {Circulation},
year = {2009},
volume = {119},
pages = {1576--1585},
number = {12},
month = mar,
abstract = {Background-- Sinoatrial node (SAN) dysfunction is frequently associated
with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker
function after termination of ATs can cause syncope and require pacemaker
implantation, but underlying mechanisms remain poorly understood.
This study examined the hypothesis that ATs impair SAN function by
altering ion channel expression. Methods and Results-- SAN tissues
were obtained from 28 control dogs and 31 dogs with 7-day atrial
tachypacing (400 bpm). Ionic currents were measured from single SAN
cells with whole-cell patch-clamp techniques. Atrial tachypacing
increased SAN recovery time in vivo by {approx}70% (P<0.01), a change
which reflects impaired SAN function. In dogs that underwent atrial
tachypacing, SAN mRNA expression (real-time reverse-transcription
polymerase chain reaction) was reduced for hyperpolarization-activated
cyclic nucleotide-gated subunits (HCN2 and HCN4) by >50% (P<0.01)
and for the {beta}-subunit minK by {approx}42% (P<0.05). SAN transcript
expression for the rapid delayed-rectifier (IKr) {alpha}-subunit
ERG, the slow delayed-rectifier (IKs) {alpha}-subunit KvLQT1, the
{beta}-subunit MiRP1, the L-type (ICaL) and T-type (ICaT) Ca2+-current
subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin
43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced
densities of the HCN-related funny current (If) and IKs by {approx}48%
(P<0.001) and {approx}34% (P<0.01), respectively, with no change
in voltage dependence or kinetics. IKr, ICaL, and ICaT were unaffected.
SAN cells lacked Ba2+-sensitive inward-rectifier currents, irrespective
of AT. SAN action potential simulations that incorporated AT-induced
alterations in If accounted for slowing of periodicity, with no additional
contribution from changes in IKs. Conclusions-- AT downregulates
SAN HCN2/4 and minK subunit expression, along with the corresponding
currents If and IKs. Tachycardia-induced remodeling of SAN ion channel
expression, particularly for the "pacemaker" subunit If, may contribute
to the clinically significant association between SAN dysfunction
and supraventricular tachyarrhythmias.},
url = {http://circ.ahajournals.org/cgi/content/abstract/119/12/1576}
}
@ARTICLE{Yelamanchili2011,
author = {Yelamanchili, Sowmya and Chaudhuri, Amrita and Flynn, Claudia and
Fox, Howard},
title = {Upregulation of cathepsin D in the caudate nucleus of primates with
experimental parkinsonism},
journal = {Molecular Neurodegeneration},
year = {2011},
volume = {6},
pages = {52},
number = {1},
abstract = {BACKGROUND:In Parkinson's disease there is progressive loss of dopamine
containing neurons in the substantia nigra pars compacta. The neuronal
damage is not limited to the substantia nigra but progresses to other
regions of brain, leading to loss of motor control as well as cognitive
abnormalities. The purpose of this study was to examine causes of
progressive damage in the caudate nucleus, which plays a major role
in motor coordination and cognition, in experimental Parkinson's
disease.RESULTS:Using chronic 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine
treatment of rhesus monkeys to model Parkinson's disease, we found
a upregulation of Cathepsin D, a lysosomal aspartic protease, in
the caudate nucleus of treated monkeys. Immunofluorescence analysis
of caudate nucleus brain tissue showed that the number of lysosomes
increased concurrently with the increase in Cathepsin D in neurons.
In vitro overexpression of Cathepsin D in a human neuroblastoma cell
line led to a significant increase in the number of the lysosomes.
Such expression also resulted in extralysosomal Cathepsin D and was
accompanied by significant neuronal death associated with caspase
activation. We examined apoptotic markers and found a strong correlation
of Cathepsin D overexpression to apoptosis.CONCLUSIONS:Following
damage to the substantia nigra resulting in experimental Parkinson's
disease, we have identified pathological changes in the caudate nucleus,
a likely site of changes leading to the progression of disease. Cathepsin
D, implicated in pathogenic mechanisms in other disorders, was increased,
and our in vitro studies revealed its overexpression leads to cellular
damage and death. This work provides important clues to the progression
of Parkinson's, and provides a new target for strategies to ameliorate
the progression of this disease.},
doi = {10.1186/1750-1326-6-52},
issn = {1750-1326},
pubmedid = {21777416},
url = {http://www.molecularneurodegeneration.com/content/6/1/52}
}
@ARTICLE{Yeoh2002,
author = {Yeoh, Eng-Juh and Ross, Mary E and Shurtleff, Sheila A and Williams,
W.Kent and Patel, Divyen and Mahfouz, Rami and Behm, Fred G and Raimondi,
Susana C and Relling, Mary V and Patel, Anami and Cheng, Cheng and
Campana, Dario and Wilkins, Dawn and Zhou, Xiaodong and Li, Jinyan
and Liu, Huiqing and Pui, Ching-Hon and Evans, William E and Naeve,
Clayton and Wong, Limsoon and Downing, James R},
title = {Classification, subtype discovery, and prediction of outcome in pediatric
acute lymphoblastic leukemia by gene expression profiling},
journal = {Cancer Cell},
year = {2002},
volume = {1},
pages = {133--143},
number = {2},
month = mar,
abstract = {Treatment of pediatric acute lymphoblastic leukemia (ALL) is based
on the concept of tailoring the intensity of therapy to a patient's
risk of relapse. To determine whether gene expression profiling could
enhance risk assignment, we used oligonucleotide microarrays to analyze
the pattern of genes expressed in leukemic blasts from 360 pediatric
ALL patients. Distinct expression profiles identified each of the
prognostically important leukemia subtypes, including T-ALL, E2A-PBX1,
BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes.
In addition, another ALL subgroup was identified based on its unique
expression profile. Examination of the genes comprising the expression
signatures provided important insights into the biology of these
leukemia subgroups. Further, within some genetic subgroups, expression
profiles identified those patients that would eventually fail therapy.
Thus, the single platform of expression profiling should enhance
the accurate risk stratification of pediatric ALL patients.},
issn = {1535-6108},
url = {http://www.sciencedirect.com/science/article/B6WWK-45J85YN-7/2/800907717fb91837abf0081894579db0}
}
@ARTICLE{Yeom2010,
author = {Yeom, Jinki and Imlay, James A. and Park, Woojun},
title = {Iron Homeostasis Affects Antibiotic-mediated Cell Death in Pseudomonas
Species},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {22689--22695},
number = {29},
month = jul,
abstract = {Antibiotics can induce cell death via a variety of action modes, including
the inhibition of transcription, ribosomal function, and cell wall
biosynthesis. In this study, we demonstrated directly that iron availability
is important to the action of antibiotics, and the ferric reductases
of Pseudomonas putida and Pseudomonas aeruginosa could accelerate
antibiotic-mediated cell death by promoting the Fenton reaction.
The modulation of reduced nicotinamide-adenine dinucleotide (NADH)
levels and iron chelation affected the actions of antibiotics. Interestingly,
the deletion of the ferric reductase gene confers more antibiotic
resistance upon cells, and its overexpression accelerates antibiotic-mediated
cell death. The results of transcriptome analysis showed that both
Pseudomonas species induce many oxidative stress genes under antibiotic
conditions, which could not be observed in ferric reductase mutants.
Our results indicate that iron homeostasis is crucial for bacterial
cell survival under antibiotics and should constitute a significant
target for boosting the action of antibiotics.},
url = {http://www.jbc.org/cgi/content/abstract/285/29/22689}
}
@ARTICLE{Yepiskoposyan2011,
author = {Yepiskoposyan, Hasmik and Aeschimann, Florian and Nilsson, Daniel
and Okoniewski, Michal and Muhlemann, Oliver},
title = {Autoregulation of the nonsense-mediated mRNA decay pathway in human
cells},
journal = {RNA},
year = {2011},
volume = {17},
pages = {2108-2118},
number = {12},
abstract = {Nonsense-mediated mRNA decay (NMD) is traditionally portrayed as a
quality-control mechanism that degrades mRNAs with truncated open
reading frames (ORFs). However, it is meanwhile clear that NMD also
contributes to the post-transcriptional gene regulation of numerous
physiological mRNAs. To identify endogenous NMD substrate mRNAs and
analyze the features that render them sensitive to NMD, we performed
transcriptome profiling of human cells depleted of the NMD factors
UPF1, SMG6, or SMG7. It revealed that mRNAs up-regulated by NMD abrogation
had a greater median 3'-UTR length compared with that of the human
mRNAome and were also enriched for 3'-UTR introns and uORFs. Intriguingly,
most mRNAs coding for NMD factors were among the NMD-sensitive transcripts,
implying that the NMD process is autoregulated. These mRNAs all possess
long 3' UTRs, and some of them harbor uORFs. Using reporter gene
assays, we demonstrated that the long 3' UTRs of UPF1, SMG5, and
SMG7 mRNAs are the main NMD-inducing features of these mRNAs, suggesting
that long 3' UTRs might be a frequent trigger of NMD.},
doi = {10.1261/rna.030247.111},
eprint = {http://rnajournal.cshlp.org/cgi/reprint/17/12/2108.pdf},
url = {http://rnajournal.cshlp.org/cgi/content/abstract/17/12/2108}
}
@ARTICLE{Ygberg2006,
author = {Ygberg, Sofia Eriksson and Clements, Mark O. and Rytkonen, Anne and
Thompson, Arthur and Holden, David W. and Hinton, Jay C. D. and Rhen,
Mikael},
title = {Polynucleotide Phosphorylase Negatively Controls spv Virulence Gene
Expression in Salmonella enterica},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {1243--1254},
number = {2},
month = feb,
abstract = {Mutational inactivation of the cold-shock-associated exoribonuclease
polynucleotide phosphorylase (PNPase; encoded by the pnp gene) in
Salmonella enterica serovar Typhimurium was previously shown to enable
the bacteria to cause chronic infection and to affect the bacterial
replication in BALB/c mice (M. O. Clements et al., Proc. Natl. Acad.
Sci. USA 99:8784-8789, 2002). Here, we report that PNPase deficiency
results in increased expression of Salmonella plasmid virulence (spv)
genes under in vitro growth conditions that allow induction of spv
expression. Furthermore, whole-genome microarray-based transcriptome
analyses of bacteria growing inside murine macrophage-like J774.A.1
cells revealed six genes as being significantly up-regulated in the
PNPase-deficient background, which included spvABC, rtcB, entC, and
STM2236. Mutational inactivation of the spvR regulator diminished
the increased expression of spv observed in the pnp mutant background,
implying that PNPase acts upstream of or at the level of SpvR. Finally,
competition experiments revealed that the growth advantage of the
pnp mutant in BALB/c mice was dependent on spvR as well. Combined,
our results support the idea that in S. enterica PNPase, apart from
being a regulator of the cold shock response, also functions in tuning
the expression of virulence genes and bacterial fitness during infection.},
url = {http://iai.asm.org/cgi/content/abstract/74/2/1243}
}
@ARTICLE{Yi2011,
author = {Yi, Hana and Cho, Yong-Joon and Won, Sungho and Lee, Jong-Eun and
Jin Yu, Hyung and Kim, Sujin and Schroth, Gary P. and Luo, Shujun
and Chun, Jongsik},
title = {Duplex-specific nuclease efficiently removes rRNA for prokaryotic
RNA-seq},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {e140},
number = {20},
abstract = {Next-generation sequencing has great potential for application in
bacterial transcriptomics. However, unlike eukaryotes, bacteria have
no clear mechanism to select mRNAs over rRNAs; therefore, rRNA removal
is a critical step in sequencing-based transcriptomics. Duplex-specific
nuclease (DSN) is an enzyme that, at high temperatures, degrades
duplex DNA in preference to single-stranded DNA. DSN treatment has
been successfully used to normalize the relative transcript abundance
in mRNA-enriched cDNA libraries from eukaryotic organisms. In this
study, we demonstrate the utility of this method to remove rRNA from
prokaryotic total RNA. We evaluated the efficacy of DSN to remove
rRNA by comparing it with the conventional subtractive hybridization
(Hyb) method. Illumina deep sequencing was performed to obtain transcriptomes
from Escherichia coli grown under four growth conditions. The results
clearly showed that our DSN treatment was more efficient at removing
rRNA than the Hyb method was, while preserving the original relative
abundance of mRNA species in bacterial cells. Therefore, we propose
that, for bacterial mRNA-seq experiments, DSN treatment should be
preferred to Hyb-based methods.},
doi = {10.1093/nar/gkr617},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/20/e140.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/20/e140}
}
@ARTICLE{Yick2009,
author = {Yick, C and Lutter, R and Grunberg, K and Bel, EH and Sterk, PJ},
title = {Isolation of High Quality RNA from the Airway Smooth Muscle in Human
Bronchial Biopsy Specimens: A Feasibility Study.},
journal = {Am. J. Respir. Crit. Care Med.},
year = {2009},
volume = {179},
pages = {A2060--},
number = {1_MeetingAbstracts},
month = apr,
url = {http://ajrccm.atsjournals.org}
}
@ARTICLE{Yilmaz2010,
author = {Yilmaz, Saliha and Boffito, Marta and Collot-Teixeira, Sophie and
De Lorenzo, Ferruccio and Waters, Laura and Fletcher, Carl and Back,
David and Pozniak, Anton and Gazzard, Brian and McGregor, John Louis},
title = {Investigation of low-dose ritonavir on human peripheral blood mononuclear
cells using gene expression whole genome microarrays},
journal = {Genomics},
year = {2010},
volume = {96},
pages = {57--65},
number = {1},
month = jul,
abstract = {Ritonavir is a protease inhibitor associated with metabolic abnormalities
and cardiovascular disease. We have investigated the effects of low-dose
ritonavir treatment on gene expression in peripheral blood mononuclear
cells (PBMC) of 10 healthy donors. Results using whole genome Illumina
microarrays show that ritonavir modulates a number of genes implicated
in lipid metabolism, inflammation and atherosclerosis. These candidate
genes are dual specificity phosphatase 1 DUSP1), Kelch domain containing
3 (KLHDC3), neutral cholesterol ester hydrolase 1 (NCEH1) and acyl-CoA
synthetase short-chain family member 2 (ACSS2). Validation experiments
using quantitative PCR showed that ritonavir (at 100 mg once daily
and 100 mg twice daily significantly down-regulated these 4 selected
candidate genes in 20 healthy individuals. Lower expression levels
of these 4 candidate genes, known to play a critical role in inflammation,
lipid metabolism and atherosclerosis, may explain ritonavir adverse
effects in patients.},
issn = {0888-7543},
keywords = {PBMC, Ritonavir, Gene expression microarray, Bioinformatics, Biomarker},
url = {http://www.sciencedirect.com/science/article/B6WG1-4YR33FN-2/2/dc13f5a6c1b5d114c0dd2914d6898c50}
}
@ARTICLE{Yin2011,
author = {Yin, Fuqiang and Pajak, Agnieszka and Chapman, Ralph and Sharpe,
Andrew and Huang, Shangzhi and Marsolais, Frederic},
title = {Analysis of common bean expressed sequence tags identifies sulfur
metabolic pathways active in seed and sulfur-rich proteins highly
expressed in the absence of phaseolin and major lectins},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {268},
number = {1},
abstract = {BACKGROUND:A deficiency in phaseolin and phytohemagglutinin is associated
with a near doubling of sulfur amino acid content in genetically
related lines of common bean (Phaseolus vulgaris), particularly cysteine,
elevated by 70%, and methionine, elevated by 10%. This mostly takes
place at the expense of an abundant non-protein amino acid, S-methyl-cysteine.
The deficiency in phaseolin and phytohemagglutinin is mainly compensated
by increased levels of the 11S globulin legumin and residual lectins.
Legumin, albumin-2, defensin and albumin-1 were previously identified
as contributing to the increased sulfur amino acid content in the
mutant line, on the basis of similarity to proteins from other legumes.RESULTS:Profiling
of free amino acid in developing seeds of the BAT93 reference genotype
revealed a biphasic accumulation of gamma-glutamyl-S-methyl-cysteine,
the main soluble form of S-methyl-cysteine, with a lag phase occurring
during storage protein accumulation. A collection of 30,147 expressed
sequence tags (ESTs) was generated from four developmental stages,
corresponding to distinct phases of gamma-glutamyl-S-methyl-cysteine
accumulation, and covering the transitions to reserve accumulation
and dessication. Analysis of gene ontology categories indicated the
occurrence of multiple sulfur metabolic pathways, including all enzymatic
activities responsible for sulfate assimilation, de novo cysteine
and methionine biosynthesis. Integration of genomic and proteomic
data enabled the identification and isolation of cDNAs coding for
legumin, albumin-2, defensin D1 and albumin-1A and -B induced in
the absence of phaseolin and phytohemagglutinin. Their deduced amino
acid sequences have a higher content of cysteine than methionine,
providing an explanation for the preferential increase of cysteine
in the mutant line.CONCLUSION:The EST collection provides a foundation
to further investigate sulfur metabolism and the differential accumulation
of sulfur amino acids in seed of common bean. Identification of sulfur-rich
proteins whose levels are elevated in seed lacking phaseolin and
phytohemagglutinin and sulfur metabolic genes may assist the improvement
of protein quality.},
doi = {10.1186/1471-2164-12-268},
issn = {1471-2164},
pubmedid = {21615926},
url = {http://www.biomedcentral.com/1471-2164/12/268}
}
@ARTICLE{Yin2009,
author = {Yin, Hu-Quan and Je, Young-Tae and Kim, Mingoo and Kim, Ju-Han and
Kong, Gu and Kang, Kyung-Sun and Kim, Hyung-Lae and Yoon, Byung-IL
and Lee, Mi-Ock and Lee, Byung-Hoon},
title = {Analysis of hepatic gene expression during fatty liver change due
to chronic ethanol administration in mice},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {235},
pages = {312--320},
number = {3},
month = mar,
abstract = {Chronic consumption of ethanol can cause cumulative liver damage that
can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic
steatosis, we investigated the global intrahepatic gene expression
profiles of livers from mice administered alcohol. Ethanol was administered
by feeding the standard Lieber-DeCarli diet, of which 36% (high dose)
and 3.6% (low dose) of the total calories were supplied from ethanol
for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples
revealed fatty changes and punctate necrosis in the high-dose group
and ballooning degeneration in the low-dose group. In total, 292
genes were identified as ethanol responsive, and several of these
differed significantly in expression compared to those of control
mice (two-way ANOVA; p < 0.05). Specifically, the expression levels
of genes involved in hepatic lipid transport and metabolism were
examined. An overall net increase in gene expression was observed
for genes involved in (i) glucose transport and glycolysis, (ii)
fatty acid influx and de novo synthesis, (iii) fatty acid esterification
to triglycerides, and (iv) cholesterol transport, de novo cholesterol
synthesis, and bile acid synthesis. Collectively, these data provide
useful information concerning the global gene expression changes
that occur due to alcohol intake and provide important insights into
the comprehensive mechanisms of chronic alcoholic steatosis.},
issn = {0041-008X},
keywords = {Ethanol, Fatty liver, Toxicogenomics, Lipid metabolism, Lipid transport,
Microarray},
url = {http://www.sciencedirect.com/science/article/B6WXH-4V9S31W-2/2/eec1a3363dcc80a45ac9ef06c2392a24}
}
@ARTICLE{Yin2007,
author = {Yin, Hu-Quan and Kim, Mingoo and Kim, Ju-Han and Kong, Gu and Kang,
Kyung-Sun and Kim, Hyung-Lae and Yoon, Byung-IL and Lee, Mi-Ock and
Lee, Byung-Hoon},
title = {Differential gene expression and lipid metabolism in fatty liver
induced by acute ethanol treatment in mice},
journal = {Toxicology and Applied Pharmacology},
year = {2007},
volume = {223},
pages = {225--233},
number = {3},
month = sep,
abstract = {Ethanol induces cumulative liver damage including steatosis, steatohepatitis
and cirrhosis. The aim of this study is to investigate the global
intrahepatic gene expression profile in the mouse liver treated with
ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered
to male ICR mice, and liver samples were obtained after 6, 24 and
72 h. Histopathological evaluation showed typical fatty livers in
the high-dose group at 24 h. Microarray analysis identified 28 genes
as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment
by the Benjamini-Hochberg multiple testing correction; these genes
displayed >= 2-fold induction or repression. The expression of genes
that are known to be involved in fatty acid synthesis was examined.
The transcript for lipogenic transcription factor, sterol regulatory
element (SRE)-binding factor 1 (Srebf1), was upregulated by acute
ethanol exposure. Of the genes known to contain SRE or SRE-like sequences
and to be regulated by SRE-binding protein 1 (SREBP1), those encoding
malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase
(Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol.
Quantitative real-time PCR confirmed the changes in the expression
levels of the selected genes. The change in the Srebf1 mRNA level
correlates well with that of the SREBP1 protein expression as well
as its binding to the promoters of the target genes. The present
study identifies differentially expressed genes that can be applied
to the biomarkers for alcohol-binge-induced fatty liver. These results
support the hypothesis by which ethanol-induced steatosis in mice
is mediated by the fatty acid synthetic pathway regulated by SREBP1.},
issn = {0041-008X},
keywords = {Ethanol, Fatty liver, Toxicogenomics, Fatty acid synthesis, Sterol
regulatory element-binding protein (SREBP), Microarray},
url = {http://www.sciencedirect.com/science/article/B6WXH-4P4295B-1/2/9719306ae6b916c9bdbe53e1eb3b8f20}
}
@ARTICLE{Yin2006,
author = {Yin, Hu-Quan and Kim, Mingoo and Kim, Ju-Han and Kong, Gu and Lee,
Mi-Ock and Kang, Kyung-Sun and Yoon, Byung-IL and Kim, Hyung-Lae
and Lee, Byung-Hoon},
title = {Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed
to Steatogenic Drug, Tetracycline},
journal = {Toxicol. Sci.},
year = {2006},
volume = {94},
pages = {206--216},
number = {1},
month = nov,
abstract = {Tetracycline is one of a group of drugs known to induce microvesicular
steatosis. In the present study, we investigated the effects of tetracycline
on gene expression in mouse liver, using Applied Biosystems Mouse
Genome Survey Microarrays. A single oral dose of 0.1 or 1 g/kg tetracycline
was administered to male ICR mice, and liver samples were obtained
after 6, 24, or 72 h. Histopathological evaluation showed microvesicular
steatosis in the high-dose group at 24 h. In total, 96 genes were
identified as tetracycline responsive. Their level of expression
differed significantly from controls (two-way analysis of variance;
p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing
correction, and displayed a twofold or greater induction or repression.
The largest groups of gene products affected by tetracycline exposure
were those involved in signal transduction, nucleic acid metabolism,
developmental processes, and protein metabolism. The expression of
genes known to be involved in lipid metabolism was examined, using
two-sample Student's t-test for each treatment group versus a corresponding
control group. The overall net effects on expression of lipid metabolism
genes indicated an increase in cholesterol and triglyceride biosynthesis
and a decrease in {beta}-oxidation of fatty acids. Our data support
a proposed mechanism for tetracycline-induced steatogenic hepatotoxicity
that involves these processes. Moreover, we demonstrated global changes
in hepatic gene expression following tetracycline exposure; many
of these genes have the potential to be used as biomarkers of exposure
to steatogenic hepatotoxic agents.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/94/1/206}
}
@ARTICLE{Yin2010,
author = {Yin, Jun and McLoughlin, Sarah and Jeffery, Ian and Glaviano, Antonino
and Kennedy, Breandan and Higgins, Desmond},
title = {Integrating multiple genome annotation databases improves the interpretation
of microarray gene expression data},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {50},
number = {1},
abstract = {BACKGROUND:The Affymetrix GeneChip is a widely used gene expression
profiling platform. Since the chips were originally designed, the
genome databases and gene definitions have been considerably updated.
Thus, more accurate interpretation of microarray data requires parallel
updating of the specificity of GeneChip probes. We propose a new
probe remapping protocol, using the zebrafish GeneChips as an example,
by removing nonspecific probes, and grouping the probes into transcript
level probe sets using an integrated zebrafish genome annotation.
This genome annotation is based on combining transcript information
from multiple databases. This new remapping protocol, especially
the new genome annotation, is shown here to be an important factor
in improving the interpretation of gene expression microarray data.RESULTS:Transcript
data from the RefSeq, GenBank and Ensembl databases were downloaded
from the UCSC genome browser, and integrated to generate a combined
zebrafish genome annotation. Affymetrix probes were filtered and
remapped according to the new annotation. The influence of transcript
collection and gene definition methods was tested using two microarray
data sets. Compared to remapping using a single database, this new
remapping protocol results in up to 20% more probes being retained
in the remapping, leading to approximately 1,000 more genes being
detected. The differentially expressed gene lists are consequently
increased by up to 30%. We are also able to detect up to three times
more alternative splicing events. A small number of the bioinformatics
predictions were confirmed using real-time PCR validation.CONCLUSIONS:By
combining gene definitions from multiple databases, it is possible
to greatly increase the numbers of genes and splice variants that
can be detected in microarray gene expression experiments.},
doi = {10.1186/1471-2164-11-50},
issn = {1471-2164},
pubmedid = {20089164},
url = {http://www.biomedcentral.com/1471-2164/11/50}
}
@ARTICLE{Yin2007a,
author = {Yin, James Q. and Zhao, Robert C.},
title = {Identifying expression of new small RNAs by microarrays},
journal = {Methods},
year = {2007},
volume = {43},
pages = {123--130},
number = {2},
month = oct,
abstract = {Although a large number of small RNAs (sRNAs) have been discovered,
it is very likely that the screens conducted so far have not reached
saturation. Recently, many methods for predicting and identifying
new sRNAs have been developed. However, it remains unclear what the
total number of sRNAs within a genome is and how many types of sRNAs
exist in plants and animals. In this article, combined methods of
dynamic programming prediction, enrichment of sRNAs, and microarray
analysis are developed to screen and evaluate a new class of sRNAs
from introns of human, protein-encoding genes. The methods used by
our laboratories to design capture probes and label enriched small
RNAs are thoroughly described here. The microarray results show that
our modified technologies are useful to enhance sensitivity and specificity
of arrays, identify expression patterns within different cells, and
discover differential expression of sRNAs during the differentiation
process of bone marrow stem cells. Accordingly, the combination of
computational prediction and microarray analysis may be a feasible
and practical approach for profiling studies of both known and predicted
small RNAs.},
booktitle = {MicroRNAs Part A},
issn = {1046-2023},
keywords = {miRNA, Small RNA, Microarray, Gene expression, Disease, Cancer},
url = {http://www.sciencedirect.com/science/article/B6WN5-4PPVFGV-7/2/c79c6e9734526fb600944a25c74e2894}
}
@ARTICLE{Yin2007b,
author = {Yin, Lei and Dale, Beverly A.},
title = {Activation of protective responses in oral epithelial cells by Fusobacterium
nucleatum and human {beta}-defensin-2},
journal = {J. Med. Microbiol.},
year = {2007},
volume = {56},
pages = {976--987},
number = {7},
month = jul,
abstract = {Oral epithelia are constantly exposed to non-pathogenic (commensal)
bacteria, but generally remain healthy and uninflamed. Fusobacterium
nucleatum, an oral commensal bacterium, strongly induces human {beta}-defensin-2
(hBD2), an antimicrobial and immunomodulatory peptide, in gingival
epithelial cells (GECs). hBD2 is also expressed in normal oral tissue
leading to the hypothesis that oral epithelia are in an activated
state with respect to innate immune responses under normal in vivo
conditions. In order to test this hypothesis, global gene expression
was evaluated in GECs in response to stimulation by an F. nucleatum
cell wall (FnCW) preparation and to hBD2 peptide. FnCW treatment
altered 829 genes, while hBD2 altered 209 genes (P<0.005, ANOVA).
Many induced genes were associated with the gene ontology categories
of immune responses and defence responses. Consistent with the hypothesis,
similar responses were activated by commensal bacteria and hBD2.
These responses included up-regulation of common antimicrobial effectors
and chemokines, and down-regulation of proliferation markers. In
addition, FnCW up-regulated multiple protease inhibitors, and suppressed
NF-{kappa}B function and the ubiquitin/proteasome system. These global
changes may protect the tissue from inflammatory damage. Both FnCW
and hBD2 also up-regulated genes that may enhance the epithelial
barrier. The findings suggest that both commensal bacteria and hBD2
activate protective responses of GECs and play an important role
in immune modulation in the oral cavity.},
url = {http://jmm.sgmjournals.org/cgi/content/abstract/56/7/976}
}
@ARTICLE{Yin2011a,
author = {Yin, Lina and Lu, Lu and Prasad, Kavita and Richfield, Eric K. and
Unger, Erica L. and Xu, Jialin and Jones, Byron C.},
title = {Genetic-based, differential susceptibility to paraquat neurotoxicity
in mice},
journal = {Neurotoxicology and Teratology},
year = {2011},
volume = {33, 3},
pages = {415–421},
abstract = {Paraquat (PQ) is an herbicide used extensively in agriculture. This
agent is also suspected to be a risk factor for Parkinson's disease
(PD) by harming nigro-striatal dopamine neurons. There is likely,
genetic-based, individual variability in susceptibility to PQ neurotoxicity
related PD. In this study, we measured the delivery of PQ to the
brain after three weekly injections of PQ at 5 mg kg-1, PQ-related
neural toxicity after three weekly injections of PQ at 1 mg kg-1or
5 mg kg-1, PQ-related iron accumulation and PQ-related gene expression
in midbrain of DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains
after a single injection of PQ at 15 mg kg-1 and 10 mg kg-1, respectively.
Results showed that compared to controls, PQ-treated B6 mice lost
greater numbers of dopaminergic neurons in the substantia nigra pars
compacta than D2 mice; however, distribution of PQ to the midbrain
was equal between the strains. PQ also significantly increased iron
concentration in the midbrain of B6 but not D2 mice. Microarray analysis
of the ventral midbrain showed greater PQ-induced changes in gene
expression in B6 compared to D2 mice. This is the first study to
report genetically-based differences in susceptibility to PQ neurotoxicity
and to understanding individual differences in vulnerability to PQ
neurotoxicity and its relation to PD in humans.},
issn = {0892-0362},
keywords = {Paraquat, Inbred mice, Substantia nigra, Gene expression, Parkinson's
disease},
url = {http://www.sciencedirect.com/science/article/pii/S0892036211000328}
}
@ARTICLE{Yin2004,
author = {Yin, Xinghua and Kidd, Grahame J. and Pioro, Erik P. and McDonough,
Jennifer and Dutta, Ranjan and Feltri, M. Laura and Wrabetz, Lawrence
and Messing, Albee and Wyatt, Ryan M. and Balice-Gordon, Rita J.
and Trapp, Bruce D.},
title = {Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional
Synaptic Terminals},
journal = {J. Neurosci.},
year = {2004},
volume = {24},
pages = {3890--3898},
number = {15},
month = apr,
abstract = {Axonal degeneration is the major cause of permanent neurological disability
in individuals with inherited diseases of myelin. Axonal and neuronal
changes that precede axonal degeneration, however, are not well characterized.
We show here that dysmyelinated lower motor neurons retract and regenerate
dysfunctional presynaptic terminals, leading to severe neurological
disability before axonal degeneration. In addition, dysmyelination
led to a decreased synaptic quantal content, an indicator of synaptic
dysfunction. The amplitude and rise time of miniature endplate potentials
were also increased, but these changes were primarily consistent
with an increase in the passive membrane properties of the transgenic
muscle fibers. Maintenance of synaptic connections should be considered
as a therapeutic target for slowing progression of neurological disability
in primary diseases of myelin.},
url = {http://www.jneurosci.org/cgi/content/abstract/24/15/3890}
}
@ARTICLE{Yin2004a,
author = {Yin, Xiaolu and Zhou, Jiangbing and Jie, Chunfa and Xing, Dongming
and Zhang, Ying},
title = {Anticancer activity and mechanism of Scutellaria barbata extract
on human lung cancer cell line A549},
journal = {Life Sciences},
year = {2004},
volume = {75},
pages = {2233--2244},
number = {18},
month = sep,
abstract = {Scutellaria barbata (S. barbata), a traditional Chinese herbal medicine
native to southern China, is widely used as an anti-inflammatory
and a diuretic in China. Several studies have indicated that extracts
of S. barbata have growth inhibitory effects on a number of human
cancers. Treatment of lung cancer, digestive system cancers, hepatoma,
breast cancer, and chorioepithelioma by S. barbata extracts was reported.
However, the mechanism underlying the antitumor activity was unclear.
In this study, we studied the growth inhibitory effect of S. barbata
and determined its mechanism of antitumor activity using human lung
cancer cell line A549. Our results showed that ethanol extracts of
S. barbata greatly inhibited A549 cell growth, with IC50 of 0.21
mg/ml. The major mechanisms of inhibition included cell apoptosis
and cytotoxic effects. cDNA microarray analysis showed that 16 genes,
involved in DNA damage, cell cycle control, nucleic acid binding
and protein phosphorylation, underwent more than 5-fold change. These
data indicated that these processes are involved in S. barbata-mediated
killing of cancer cells. A surprising finding is that CD209, related
to dendritic cell (DC) function, was dramatically downregulated by
102-fold. Further functional studies are needed to assess the role
of the array-identified genes in S. barbata mediated anticancer activity.},
issn = {0024-3205},
keywords = {Cancer, Herbal medicine, Scutellaria barbata},
url = {http://www.sciencedirect.com/science/article/B6T99-4D1VDV5-2/2/23c8cfdb38e7fb6ba3f9eca6dd8d64b2}
}
@ARTICLE{YIN2005,
author = {YIN, Xiao-lin and FANG, Kai-tai and LIANG, Yi-zeng and WONG, Ricky
NS and WYHA, Amber},
title = {Assessing phylogenetic relationships of Lycium samples using RAPD
and entropy theory1},
journal = {Acta Pharmacologica Sinica},
year = {2005},
volume = {26},
pages = {1217--1224},
number = {10},
abstract = {Abstract Aim: To evaluate the phylogenetic relationships among related
species of Lycium samples. Methods: Random amplified polymorphic
DNA (RAPD) fingerprinting and lab-on-a-chip electrophoresis techniques
were used to analyze the characteristics of Lycium species. Seven
species and 3 varieties of Lycium were studied. Based on RAPD fingerprint
data obtained from 11 primers, we proposed a new index, called dispersivity,
using entropy theory and projection methods to depict the diversity
of the DNA fingerprints. Results: Using the proposed dispersivity,
primers were sorted and the dendrograms of the 7 species and 3 varieties
of Lycium were constructed synthetically by merging primer information.
Conclusion: Phylogenetic relationships among Lycium samples were
constructed synthetically based on RAPD fingerprint data generated
from 11 primers.},
issn = {1745-7254},
keywords = {DNA fingerprinting, RAPD technique, lab-on-a-chip, entropy, UPGMA},
publisher = {Blackwell Science Pty},
url = {http://dx.doi.org/10.1111/j.1745-7254.2005.00197.x}
}
@ARTICLE{Yip2012,
author = {Yip, Stephen and Butterfield, Yaron S and Morozova, Olena and Chittaranjan,
Suganthi and Blough, Michael D and An, Jianghong and Birol, Inanc
and Chesnelong, Charles and Chiu, Readman and Chuah, Eric and Corbett,
Richard and Docking, Rod and Firme, Marlo and Hirst, Martin and Jackman,
Shaun and Karsan, Aly and Li, Haiyan and Louis, David N and Maslova,
Alexandra and Moore, Richard and Moradian, Annie and Mungall, Karen
L and Perizzolo, Marco and Qian, Jenny and Roldan, Gloria and Smith,
Eric E and Tamura-Wells, Jessica and Thiessen, Nina and Varhol, Richard
and Weiss, Samuel and Wu, Wei and Young, Sean and Zhao, Yongjun and
Mungall, Andrew J and Jones, Steven JM and Morin, Gregg B and Chan,
Jennifer A and Cairncross, J Gregory and Marra, Marco A},
title = {Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish
oligodendrogliomas from other cancers},
journal = {The Journal of Pathology},
year = {2012},
volume = {226},
pages = {7--16},
number = {1},
abstract = {Oligodendroglioma is characterized by unique clinical, pathological,
and genetic features. Recurrent losses of chromosomes 1p and 19q
are strongly associated with this brain cancer but knowledge of the
identity and function of the genes affected by these alterations
is limited. We performed exome sequencing on a discovery set of 16
oligodendrogliomas with 1p/19q co-deletion to identify new molecular
features at base-pair resolution. As anticipated, there was a high
rate of IDH mutations: all cases had mutations in either IDH1 (14/16)
or IDH2 (2/16). In addition, we discovered somatic mutations and
insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16
tumours. These discovery set mutations were validated by deep sequencing
of 13 additional tumours, which revealed seven others with CIC mutations,
thus bringing the overall mutation rate in oligodendrogliomas in
this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas
and oligoastrocytomas without 1p/19q loss revealed that CIC alterations
were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic
mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon
5 within an annotated DNA-interacting domain and three were in exon
20 within an annotated protein-interacting domain. The remaining
nine were found in other exons and frequently included truncations.
CIC mutations were highly associated with oligodendroglioma histology,
1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we
observed no differences in the clinical outcomes of CIC mutant versus
wild-type tumours, in a background of 1p/19q co-deletion, hemizygous
CIC mutations are likely important. We hypothesize that the mutant
CIC on the single retained 19q allele is linked to the pathogenesis
of oligodendrogliomas with IDH mutation. Our detailed study of genetic
aberrations in oligodendroglioma suggests a functional interaction
between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion. Copyright
© 2011 Pathological Society of Great Britain and Ireland. Published
by John Wiley & Sons, Ltd.},
doi = {10.1002/path.2995},
issn = {1096-9896},
keywords = {glioma, oligodendroglioma, next-generation sequencing, Capicua, IDH1},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2995}
}
@ARTICLE{Yloestalo2008,
author = {Ylöstalo, Joni and Bazhanov, Nikolay and Prockop, Darwin J.},
title = {Reversible commitment to differentiation by human multipotent stromal
cells in single-cell-derived colonies},
journal = {Experimental Hematology},
year = {2008},
volume = {36},
pages = {1390--1402},
number = {10},
month = oct,
abstract = {Objective Human multipotent stromal cells readily form single-cell-derived
colonies when plated at clonal densities. However, the colonies are
heterogeneous because cells from a colony form new colonies that
vary in size and differentiation potential when replated at clonal
densities. The experiments here tested the hypothesis that cells
in the inner regions of colonies are partially differentiated, but
the differentiation is reversible.Materials and Methods Cells were
separately isolated from the dense inner (IN) regions and less-dense
outer regions (OUT) of single-cell-derived colonies. Cells were then
compared by assays of their transcriptomes and proteins, and for
clonogenicity and differentiation.Results IN cells expressed fewer
cell-cycle genes and higher levels of genes for extracellular matrix
than the OUT cells. When transferred to differentiation medium, differentiation
of the colonies occurred primarily in the IN regions. However, the
IN cells were indistinguishable from OUT cells when replated at clonal
densities and assayed for rates of propagation and clonogenicity.
Also, colonies formed by IN cells were similar to colonies formed
by OUT cells because they had distinct IN and OUT regions. Cultures
of IN and OUT cells remained indistinguishable through multiple passages
(30 to 75 population doublings), and both cells formed colonies that
were looser and less dense as they were expanded.Conclusions The
results demonstrated that cells in the IN region of single-cell-derived
colonies are partially differentiated, but the differentiation can
be reversed by replating the cells at clonal densities.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4SYDB0H-5/2/94e0dd5cb9c4dd7576b58078f2db8c60}
}
@ARTICLE{Yokoe2008,
author = {Yokoe, Takeshi and Tanaka, Fumiaki and Mimori, Koshi and Inoue, Hiroshi
and Ohmachi, Takahiro and Kusunoki, Masato and Mori, Masaki},
title = {Efficient Identification of a Novel Cancer/Testis Antigen for Immunotherapy
Using Three-Step Microarray Analysis},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {1074--1082},
number = {4},
month = feb,
abstract = {Advanced technology in molecular biology has provided us powerful
tools for the diagnosis and treatment for cancer. We herein adopted
a new methodology to identify a novel cancer/testis (CT) antigen
with high frequency of expression in colorectal cancer as follows:
(a) combining laser microdissection and cDNA microarray was used
to analyze the gene expression profile of colorectal cancer cells;
(b) genes overexpressed in testis and underexpressed in normal colon
epithelium were analyzed using cDNA microarray; and (c) the gene
expression profile of colorectal cancer cells was compared with that
of normal testis. Using this methodology, we selected 38 candidates
for CT antigen. Among these genes, we identified a novel CT antigen,
serine/threonine kinase 31 (STK31), which was previously reported
as a gene expressed in spermatogonia. Reverse transcription-PCR analysis
showed that STK31 gene expression levels in cancer samples were significantly
higher (P < 0.0001) than those in normal samples. The STK31 gene
was frequently expressed not only in colorectal cancer but also in
gastric and esophageal cancer. Moreover, STK31 peptide was able to
elicit specific CTLs and induced CTLs lysed either peptide-loading
or endogenously STK31-expressing target cells. These results showed
that the new methodology in this study facilitated identification
of CT antigens and that STK31 may be a candidate for cancer immunotherapy
against gastrointestinal cancer. [Cancer Res 2008;68(4):1074-82]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/4/1074}
}
@ARTICLE{Yokoi2011,
author = {Yokoi, Akira and Kotake, Yoshihiko and Takahashi, Kentaro and Kadowaki,
Tadashi and Matsumoto, Yoshiko and Minoshima, Yukinori and Sugi,
Naoko H. and Sagane, Koji and Hamaguchi, Makoto and Iwata, Masao
and Mizui, Yoshiharu},
title = {Biological validation that SF3b is a target of the antitumor macrolide
pladienolide},
journal = {FEBS Journal},
year = {2011},
volume = {278},
pages = {4870--4880},
number = {24},
abstract = {Pladienolide is a naturally occurring macrolide that binds to the
SF3b complex to inhibit mRNA splicing. It has not been fully validated
whether the splicing impairment is a relevant mechanism for the potent
antitumor activity of pladienolide. We established pladienolide-resistant
clones from WiDr and DLD1 colorectal cancer cells that were insensitive
to the inhibitory action of pladienolide on cell proliferation and
splicing. An mRNA-Seq differential analysis revealed that these two
cell lines have an identical mutation at Arg1074 in the gene for
SF3B1, which encodes a subunit of the SF3b complex. Reverse expression
of the mutant protein transferred pladienolide resistance to WiDr
cells. Furthermore, immunoprecipitation analysis using a radiolabeled
probe showed that the mutation impaired the binding affinity of paldienolide
to its target. These results clearly demonstrate that pladienolide
exerts its potent activity by targeting SF3b and also suggest that
inhibition of SF3b is a promising drug target for anticancer therapy.Structured
digital abstract * • SF3B1physically interacts with SF3B2and SF3B3by anti
bait coimmunoprecipitation (View interaction)},
doi = {10.1111/j.1742-4658.2011.08387.x},
issn = {1742-4658},
keywords = {antitumor activity, pladienolide, resistant mutation, SF3b, splicing
inhibitor},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1742-4658.2011.08387.x}
}
@ARTICLE{Yokomizo2008,
author = {Yokomizo, Tomomasa and Hasegawa, Kazuteru and Ishitobi, Hiroyuki
and Osato, Motomi and Ema, Masatsugu and Ito, Yoshiaki and Yamamoto,
Masayuki and Takahashi, Satoru},
title = {Runx1 is involved in primitive erythropoiesis in the mouse},
journal = {Blood},
year = {2008},
volume = {111},
pages = {4075--4080},
number = {8},
month = apr,
abstract = {Targeted disruption of the Runx1/ AML1 gene in mice has demonstrated
that it is required for the emergence of definitive hematopoietic
cells but that it is not essential for the formation of primitive
erythrocytes. These findings led to the conclusion that Runx1 is
a stage-specific transcription factor acting only during definitive
hematopoiesis. However, the zebrafish and Xenopus homologs of Runx1
have been shown to play roles in primitive hematopoiesis, suggesting
that mouse Runx1 might also be involved in the development of primitive
lineages. In this study, we show that primitive erythrocytes in Runx1-/-
mice display abnormal morphology and reduced expression of Ter119,
Erythroid Kruppel-like factor (EKLF, KLF1), and GATA-1. These results
suggest that mouse Runx1 plays a role in the development of both
primitive and definitive hematopoietic cells.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/8/4075}
}
@ARTICLE{Yokota2011,
author = {Hirofumi Yokota and Sayaka Eguchi and Makoto Nakai},
title = {Development of an in vitro binding assay for ecdysone receptor of
mysid shrimp (Americamysis bahia)},
journal = {Aquatic Toxicology},
year = {2011},
volume = {105},
pages = {708 - 716},
number = {3–4},
abstract = {A global effort has been made to establish screening and testing methods
that can identify the effects of endocrine-disrupting chemicals (EDCs)
on invertebrates. The purpose of our study was to develop an in vitro
receptor binding assay for ecdysone receptor (EcR) in mysid shrimp
(Americamysis bahia). We cloned mysid shrimp EcR cDNA (2888 nucleotides)
and ultraspiracle (USP) cDNA (2116 nucleotides), and determined that
they encode predicted proteins of length 570 and 410 amino acids,
respectively. The deduced amino acid sequences of these proteins
shared 36–71% homology for EcR and 44–65% for USP with those
of other arthropods. Phylogenetic analysis revealed that mysid shrimp
EcR was classified into an independent cluster together with the
EcRs of another mysid species, Neomysis integer and the cluster diverged
early from those of the other taxonomic orders of crustaceans. We
then expressed the ligand-binding domains (DEF regions) of mysid
shrimp EcR (abEcRdef) and USP (abUSPdef) as glutathione S-transferase
(GST)-fusion peptides in Escherichia coli. After purifying the fusion
peptides by affinity chromatography and removing the GST labels,
we subjected the peptides to a ligand–receptor binding assay. [3H]-ponasterone
A did not bind to abEcRdef or abUSPdef peptides alone but bound strongly
to the abEcRdef/abUSPdef mixture with dissociation constant (Kd) = 2.14 nM.
Competitive binding assays showed that the IC50 values for ponasterone
A, muristerone A, 20-hydroxyecdysone, and α-ecdysone were 1.2, 1.9,
35, and 1200 nM, respectively. In contrast, the IC50 values
for two dibenzoylhydrazine ligands (tebufenozide and chromafenozide)
were >1.0 × 105 nM. The intra- and inter-assay
coefficient of variation values for the IC50 values of 20-hydroxyecdysone
were 14.7% (n = 5) and 16.1% (n = 8), respectively.
Our results indicate that the binding assay with a mixture of abEcRdef
and abUSPdef can be used to screen compounds with a broad range of
binding affinities for crustacean EcRs.},
doi = {10.1016/j.aquatox.2011.09.008},
issn = {0166-445X},
keywords = {Mysids},
url = {http://www.sciencedirect.com/science/article/pii/S0166445X11002566}
}
@ARTICLE{Yokoyama2007,
author = {Yokoyama, Akihiro and Yamashino, Takafumi and Amano, Yu-Ichiro and
Tajima, Yoshinori and Imamura, Aya and Sakakibara, Hitoshi and Mizuno,
Takeshi},
title = {Type-B ARR Transcription Factors, ARR10 and ARR12, are Implicated
in Cytokinin-Mediated Regulation of Protoxylem Differentiation in
Roots of Arabidopsis thaliana},
journal = {Plant Cell Physiol.},
year = {2007},
volume = {48},
pages = {84--96},
number = {1},
month = jan,
abstract = {In the phosphorelay-mediated cytokinin signal transduction of Arabidopsis
thaliana, certain members of the type-B authentic response regulator
(ARR) family are implicated in the regulatory networks that are primarily
propagated by the cytokinin-receptors [authentic histidine kinases
(AHKs)]. Clarification of the involvement of each type-B ARR transcription
factor in cytokinin-responsive phenomena is still at a very early
stage. Here we analyzed the redundant function of two type-B ARR
genes, ARR10 and ARR12, by constructing an arr10/arr12 double mutant.
The resulting mutant plants showed stronger phenotypes with special
reference to the cytokinin action in roots (e.g. inhibition of root
elongation, green callus formation from root explants) than those
for each single mutant, suggesting that ARR10 and ARR12 redundantly
play an important role in the cytokinin signaling in roots. This
idea was further supported by results from root-specific microarray
analyses with the double mutant plant. We also showed that ARR10
and ARR12 are involved in the AHK-dependent signaling pathway that
negatively regulates protoxylem specification in root vascular tissues.
When the double mutant is combined with an arr1 allele, the resultant
arr1/arr10/arr12 triple mutant showed phenotypes displaying a very
poor growth, quite similar to those of the wooden leg (wol) mutant
that virtually lacks cytokinin receptor activities in plants. In
this triple arr mutant, the specification of root vascular tissues
is also affected as severely as in wol. Taken together, we propose
that ARR10 and ARR12, together with ARR1, redundantly play pivotal
roles in the AHK-dependent phosphorelay signaling in response to
cytokinin in roots.},
url = {http://pcp.oxfordjournals.org/cgi/content/abstract/48/1/84}
}
@ARTICLE{Yokoyama2008,
author = {Yokoyama, Yuko and Grunebach, Frank and Schmidt, Susanne M. and Heine,
Annkristin and Hantschel, Maik and Stevanovic, Stefan and Rammensee,
Hans-Georg and Brossart, Peter},
title = {Matrilysin (MMP-7) Is a Novel Broadly Expressed Tumor Antigen Recognized
by Antigen-Specific T Cells},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {5503--5511},
number = {17},
month = sep,
abstract = {Purpose: A prerequisite for the development of vaccination strategies
is the identification and characterization of relevant tumor-associated
antigen. Using microarray and reverse transcription-PCR analysis,
we found matrix metalloproteinase (MMP)-7 to be extensively up-regulated
in renal cell carcinomas and expressed in a broad variety of malignant
cells. MMP-7 can promote cancer invasion and angiogenesis by proteolytic
cleavage of extracellular matrix and basement membrane proteins,
thus making it a promising target in the context of immunotherapies.
Experimental Design: To analyze the possible use of MMP-7 as a tumor-associated
antigen, specific CTLs were induced using monocyte-derived dendritic
cells electroporated with MMP-7-mRNA. In addition, to better characterize
the fine specificity of these CTLs, MMP-7 MHC class I ligands were
isolated and characterized in renal cell carcinoma tissue, which
overexpressed MMP-7, by mass spectrometry-based peptide sequencing.
Using this approach, we identified a novel HLA-A3-binding antigenic
MMP-7 peptide. CTLs generated from healthy donors by in vitro priming
with dendritic cells, pulsed with the novel peptide, were used as
effectors in 51Cr-release assays. Results: The induced CTLs elicited
an antigen-specific and HLA-restricted cytolytic activity against
tumor cells endogenously expressing the MMP-7 protein. Furthermore,
we were able to induce MMP-7-specific CTLs using peripheral blood
mononuclear cells from a patient with acute lymphoblastic leukemia
capable of recognizing the autologous leukemic blasts while sparing
nonmalignant cells. Conclusions: Our study describes the identification
of a novel broadly expressed T-cell epitope derived from the MMP-7
protein that represents an interesting candidate to be applied in
immunotherapies of human malignancies targeting both tumor cells
and neovascularization.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/17/5503}
}
@ARTICLE{Yomoda2008,
author = {Yomoda, Jun-ichiro and Muraki, Michiko and Kataoka, Naoyuki and Hosoya,
Takamitsu and Suzuki, Masaaki and Hagiwara, Masatoshi and Kimura,
Hiroshi},
title = {Combination of Clk family kinase and SRp75 modulates alternative
splicing of Adenovirus E1A},
journal = {Genes Cells},
year = {2008},
volume = {13},
pages = {233--244},
number = {3},
month = mar,
abstract = {SR proteins are non-snRNP splicing factors harbouring a domain rich
in Arg-Ser repeats, which are extensively phosphorylated by several
kinases. We performed a comparative study of different SR kinases,
including SRPK, Clk, PRP4 and DYRK, and found that only Clks efficiently
altered 5' splice site selection of Adenovirus E1A. The phosphorylation
state of SR proteins was examined using a phospho-SR specific antibody
mAb1H4 and a 75 kDa protein was most evidently hyperphosphorylated
by Clks. Administration of TG003, a specific inhibitor for the Clk
family members, specifically and rapidly induced dephosphorylation
of 75 kDa SR protein. Imaging with mRFP-SRp75 in living cells revealed
that its nuclear distribution was rapidly altered upon inhibition
of the Clk activity by TG003. Co-transfection experiments demonstrated
that HA-tagged SRp75 was hyperphosphorylated by Clk family members,
but not by other SR kinases. These results indicate that Clks specifically
hyperphosphorylate SRp75. Furthermore, SRp75 over-expression promoted
the selection of 12S 5' splice site in E1A pre-mRNA, which is stimulated
by co-expression of Clks. These results suggest that the specific
combination of SR protein and SR kinase plays a distinct role in
alternative splicing through dynamic balance of phosphorylation.},
url = {http://www.genestocellsonline.org/cgi/content/abstract/13/3/233}
}
@ARTICLE{Yono2005,
author = {Yono, Makoto and Foster, Jr., Harris E. and Shin, David and Mane,
Shrikant and Latifpour, Jamshid},
title = {Molecular classification of doxazosin-induced alterations in the
rat prostate using gene expression profiling},
journal = {Life Sciences},
year = {2005},
volume = {77},
pages = {470--479},
number = {4},
month = jun,
abstract = {We investigated molecular changes that occurred during chronic administration
of doxazosin, an [alpha]1-adrenoceptor (AR) antagonist, using Affymetrix
GeneChip analysis of gene expression. Rats were treated with doxazosin
(4 mg/kg/day subcutaneously, supplemented with 4 mg/kg/day orally)
for 12 weeks. Labeled cRNA was prepared and the subsequent hybridization
to rat 230A arrays was performed. The alterations in gene expression
levels of candidate genes identified by microarray analysis with
potential biological relevance were verified by real-time reverse
transcription polymerase chain reaction (RT-PCR) using SYBR Green
I. Doxazosin treated rats had significantly heavier prostates compared
to control rats. Microarray analysis revealed that chronic doxazosin
treatment caused changes in the expression levels of 625 genes, of
which 39 were related to cell death, necrosis, growth, proliferation
and G-protein signalling pathways in the rat prostate. Furthermore,
RT-PCR experiments, in accord with the microarray analysis, indicated
that chronic doxazosin treatment caused an up-regulation in the mRNA
expression level of clusterin, an antiapoptotic mediator, and epiregulin,
a mitogen, in the ventral and dorsolateral prostate, respectively.
These findings, that demonstrate chronic doxazosin administration
causes significant changes in the expression of several hundred genes
in the rat prostate, may provide insight into the long-term efficacy
of [alpha]1-AR antagonists in the treatment of benign prostatic hyperplasia.},
issn = {0024-3205},
keywords = {[alpha]1-Adrenoceptors, Doxazosin, Prostate, Microarray},
url = {http://www.sciencedirect.com/science/article/B6T99-4FDNBXC-7/2/e5efd0302e13fc60de5543459c220bc4}
}
@ARTICLE{Yono2008,
author = {Yono, Makoto and Mane, Shrikant M. and Lin, Aiping and Weiss, Robert
M. and Latifpour, Jamshid},
title = {Differential effects of diabetes induced by streptozotocin and that
develops spontaneously on prostate growth in Bio Breeding (BB) rats},
journal = {Life Sciences},
year = {2008},
volume = {83},
pages = {192--197},
number = {5-6},
month = aug,
abstract = {We investigated molecular changes in the response to insulin in prostates
of spontaneously developed (Bio Breeding) and streptozotocin (STZ)-induced
diabetic rats that received sufficient amounts (euglycemic group),
or suboptimal doses (hyperglycemic group) of insulin for 32 weeks,
using Affymetrix GeneChip analysis of gene expression. Alterations
in gene expression levels identified by microarray analysis, having
potential biological relevance to prostate growth, were verified
by real-time reverse transcription polymerase chain reaction (RT-PCR).
A significant decrease in the weight of ventral prostate was observed
in the hyperglycemic STZ-induced but not spontaneously developed
diabetic group. Microarray analysis revealed that gene expression
profiles were distinctly different in each region of the prostate,
and that hyperglycemic diabetes in spontaneously developed and STZ-diabetic
rats was associated with differential changes in the prostatic expression
levels of 856 genes, of which 35 were related to cell growth, proliferation
and death. RT-PCR data verified significant differences in the mRNA
expression levels of Igfbp6, Tieg, and Clu between euglycemic and
hyperglycemic groups, whereas expression levels of these genes in
control and euglycemic diabetic groups were not significantly different.
In ventral prostate, the mRNA expression levels of Igfbp6 and Tieg
were significantly higher in the hyperglycemic STZ-induced diabetic
than in the hyperglycemic spontaneously diabetic BBDP/Wor rats. Our
data demonstrate that the diabetes induced by STZ in the BBDR/Wor
rats affects prostate growth and the molecular response to insulin
differently than that observed in BBDP/Wor rats that develop diabetes
spontaneously.},
issn = {0024-3205},
keywords = {BB rats, Spontaneous diabetes, STZ-induced diabetes, Prostate},
url = {http://www.sciencedirect.com/science/article/B6T99-4ST3YRV-1/2/4aa1ae884eda5f1d7027a6fe41f99cf9}
}
@ARTICLE{Yoo2010,
author = {Yoo, Mi-Jeong and Chanderbali, André S. and Altman, Naomi S. and
Soltis, Pamela S. and Soltis, Douglas E.},
title = {Evolutionary trends in the floral transcriptome: insights from one
of the basalmost angiosperms, the water lily Nuphar advena (Nymphaeaceae)},
journal = {The Plant Journal},
year = {2010},
volume = {64},
pages = {687--698},
number = {4},
abstract = {Summary Current understanding of floral developmental genetics comes
primarily from the core eudicot model Arabidopsis thaliana. Here,
we explore the floral transcriptome of the basal angiosperm, Nuphar
advena (water lily), for insights into the ancestral developmental
program of flowers. We identify several thousand Nuphar genes with
significantly upregulated floral expression, including homologs of
the well-known ABCE floral regulators, deployed in broadly overlapping
transcriptional programs across floral organ categories. Strong similarities
in the expression profiles of different organ categories in Nuphar
flowers are shared with the magnoliid Persea americana (avocado),
in contrast to the largely organ-specific transcriptional cascades
evident in Arabidopsis, supporting the inference that this is the
ancestral condition in angiosperms. In contrast to most eudicots,
floral organs are weakly differentiated in Nuphar and Persea, with
staminodial intermediates between stamens and perianth in Nuphar,
and between stamens and carpels in Persea. Consequently, the predominantly
organ-specific transcriptional programs that characterize Arabidopsis
flowers (and perhaps other eudicots) are derived, and correlate with
a shift towards morphologically distinct floral organs, including
differentiated sepals and petals, and a perianth distinct from stamens
and carpels. Our findings suggest that the genetic regulation of
more spatially discrete transcriptional programs underlies the evolution
of floral morphology.},
doi = {10.1111/j.1365-313X.2010.04357.x},
issn = {1365-313X},
keywords = {Nuphar, floral developmental genetics, floral evolution, transcriptome
profiling, ABCE model},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-313X.2010.04357.x}
}
@ARTICLE{Yoon2011,
author = {Yoon, Hyunjin and Ansong, Charles and McDermott, Jason and Gritsenko,
Marina and Smith, Richard and Heffron, Fred and Adkins, Joshua},
title = {Systems analysis of multiple regulator perturbations allows discovery
of virulence factors in Salmonella},
journal = {BMC Systems Biology},
year = {2011},
volume = {5},
pages = {100},
number = {1},
abstract = {BACKGROUND:Systemic bacterial infections are highly regulated and
complex processes that are orchestrated by numerous virulence factors.
Genes that are coordinately controlled by the set of regulators required
for systemic infection are potentially required for pathogenicity.RESULTS:In
this study we present a systems biology approach in which sample-matched
multi-omic measurements of fourteen virulence-essential regulator
mutants were coupled with computational network analysis to efficiently
identify Salmonella virulence factors. Immunoblot experiments verified
network-predicted virulence factors and a subset was determined to
be secreted into the host cytoplasm, suggesting that they are virulence
factors directly interacting with host cellular components. Two of
these, SrfN and PagK2, were required for full mouse virulence and
were shown to be translocated independent of either of the type III
secretion systems in Salmonella or the type III injectisome-related
flagellar mechanism.CONCLUSIONS:Integrating multi-omic datasets from
Salmonella mutants lacking virulence regulators not only identified
novel virulence factors but also defined a new class of translocated
effectors involved in pathogenesis. The success of this strategy
at discovery of known and novel virulence factors suggests that the
approach may have applicability for other bacterial pathogens.},
doi = {10.1186/1752-0509-5-100},
issn = {1752-0509},
pubmedid = {21711513},
url = {http://www.biomedcentral.com/1752-0509/5/100}
}
@ARTICLE{Yoon2009,
author = {Yoon, Jung Hae and Chandrasekharan, Kumaran and Xu, Rui and Glass,
Matthew and Singhal, Neha and Martin, Paul T.},
title = {The synaptic CT carbohydrate modulates binding and expression of
extracellular matrix proteins in skeletal muscle: Partial dependence
on utrophin},
journal = {Molecular and Cellular Neuroscience},
year = {2009},
volume = {41},
pages = {448--463},
number = {4},
month = jul,
abstract = {The CT carbohydrate, Neu5Ac/Neu5Gc[alpha]2,3[GalNAc[beta]1,4]Gal[beta]1,4GlcNAc[beta]-,
is specifically expressed at the neuromuscular junction in skeletal
myofibers of adult vertebrates. When Galgt2, the glycosyltransferase
that creates the synaptic [beta]1,4GalNAc portion of this glycan,
is overexpressed in extrasynaptic regions of the myofiber membrane,
[alpha] dystroglycan becomes glycosylated with the CT carbohydrate
and this coincides with the ectopic expression of synaptic dystroglycan-binding
proteins, including laminin [alpha]4, laminin [alpha]5, and utrophin.
Here we show that both synaptic and extrasynaptic forms of laminin
and agrin have increased binding to the CT carbohydrate compared
to sialyl-N-acetyllactosamine, its extrasynaptically expressed precursor.
Muscle laminins also show increased binding to CT-glycosylated muscle
[alpha] dystroglycan relative to its non-CT-containing glycoforms.
Overexpression of Galgt2 in transgenic mouse skeletal muscle increased
the mRNA expression of extracellular matrix (ECM) genes, including
agrin and laminin [alpha]5, as well as utrophin, integrin [alpha]7,
and neuregulin. Increased expression of ECM proteins in Galgt2 transgenic
skeletal muscles was partially dependent on utrophin, but utrophin
was not required for Galgt2-induced changes in muscle growth or neuromuscular
development. These experiments demonstrate that overexpression of
a synaptic carbohydrate can increase both ECM binding to [alpha]
dystroglycan and ECM expression in skeletal muscle, and they suggest
a mechanism by which Galgt2 overexpression may inhibit muscular dystrophy
and affect neuromuscular development.},
issn = {1044-7431},
keywords = {Dystroglycan, Laminin, Neuromuscular junction, Synapse, Neuregulin,
Utrophin, Glycosylation, Agrin, Integrin, Muscular dystrophy, Muscle},
url = {http://www.sciencedirect.com/science/article/B6WNB-4W8VW32-2/2/2396f182e0d2ea1aaea1890a6d074ecf}
}
@ARTICLE{Yoon2010,
author = {Yoon, Sena and Choi, Young-Chul and Lee, Suman and Jeong, Yongsu
and Yoon, Jaeseung and Baek, Kwanghee},
title = {Induction of growth arrest by miR-542-3p that targets survivin},
journal = {FEBS Lett},
year = {2010},
volume = {584},
pages = {4048--4052},
number = {18},
month = sep,
abstract = {Survivin is a protein which functions as a mitotic regulator as well
as apoptosis inhibitor. In this study, we show that introduction
of synthetic miR-542-3p mimetic reduced both mRNA and protein levels
of survivin. In A549 cells, luciferase reporter assay revealed that
miR-542-3p targeted predicted binding sites in the 3′-untranslated
region (3′-UTR) of survivin. We also demonstrate that ectopic expression
of miR-542-3p inhibited cell proliferation by inducing Gap 1 (G1)
and Gap 2/Mitosis (G2/M) cell cycle arrest. Collectively, these results
suggest that survivin is a direct target of miR-542-3p and growth
inhibition by miR-542-3p may have a potential utility as an anti-cancer
therapy.},
issn = {0014-5793},
keywords = {miRNA, microRNA, G1, Gap 1, G2/M, Gap 2/Mitosis, 3′-UTR, 3′-untranslated
region, CDK, cyclin-dependent kinase, E2F3, E2 promoter binding factor
3, IAP, inhibitor of apoptosis, CPC, chromosomal passenger complex,
rRNA, ribosomal RNA, MicroRNA, miR-542-3p, Cell cycle arrest, Survivin,
18S ribosomal RNA},
publisher = {Elsevier Science B.V.},
refid = {S0014-5793(10)00681-2},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0014579310006812?showall=true}
}
@ARTICLE{Yoon2011a,
author = {Sam S. Yoon and Dan G. Duda and Daniel L. Karl and Tae-Min Kim and
Avinash R. Kambadakone and Yen-Lin Chen and Courtney Rothrock and
Andrew E. Rosenberg and G. Petur Nielsen and David G. Kirsch and
Edwin Choy and David C. Harmon and Francis J. Hornicek and Jonathan
Dreyfuss and Marek Ancukiewicz and Dushyant V. Sahani and Peter J.
Park and Rakesh K. Jain and Thomas F. DeLaney},
title = {Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable
Soft Tissue Sarcomas},
journal = {International Journal of Radiation Oncology*Biology*Physics},
year = {2011},
volume = {81},
pages = {1081 - 1090},
number = {4},
abstract = {Purpose Numerous preclinical studies have demonstrated that angiogenesis
inhibitors can increase the efficacy of radiotherapy (RT). We sought
to examine the safety and efficacy of bevacizumab (BV) and RT in
soft tissue sarcomas and explore biomarkers to help determine the
treatment response. Methods and Materials Patients with ≥5 cm,
intermediate- or high-grade soft tissue sarcomas at significant risk
of local recurrence received neoadjuvant BV alone followed by BV
plus RT before surgical resection. Correlative science studies included
analysis of the serial blood and tumor samples and serial perfusion
computed tomography scans. Results The 20 patients had a median tumor
size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis
tumors. The neoadjuvant treatment was well tolerated, with only 4
patients having Grade 3 toxicities (hypertension, liver function
test elevation). BV plus RT resulted in ≥80% pathologic necrosis
in 9 (45%) of 20 tumors, more than double the historical rate seen
with RT alone. Three patients had a complete pathologic response.
The median microvessel density decreased 53% after BV alone (p <.05).
After combination therapy, the median tumor cell proliferation decreased
by 73%, apoptosis increased 10.4-fold, and the blood flow, blood
volume, and permeability surface area decreased by 62–72% (p <.05).
Analysis of gene expression microarrays of untreated tumors identified
a 24-gene signature for treatment response. The microvessel density
and circulating progenitor cells at baseline and the reduction in
microvessel density and plasma soluble c-KIT with BV therapy also
correlated with a good pathologic response (p <.05). After a median
follow-up of 20 months, only 1 patient had developed local recurrence.
Conclusions The results from the present exploratory study indicated
that BV increases the efficacy of RT against soft tissue sarcomas
and might reduce the incidence of local recurrence. Thus, this regimen
warrants additional investigation. Gene expression profiles and other
tissue and circulating biomarkers showed promising correlations with
treatment response.},
doi = {10.1016/j.ijrobp.2010.07.024},
issn = {0360-3016},
keywords = {Sarcoma},
url = {http://www.sciencedirect.com/science/article/pii/S0360301610009557}
}
@ARTICLE{Yoon2006,
author = {Yoon, Se-Jin and Kim, Kyeoung-Hwa and Chung, Hyung-Min and Choi,
Dong-Hee and Lee, Woo-Sik and Cha, Kwang-Yul and Lee, Kyung-Ah},
title = {Gene expression profiling of early follicular development in primordial,
primary, and secondary follicles},
journal = {Fertility and Sterility},
year = {2006},
volume = {85},
pages = {193--203},
number = {1},
month = jan,
abstract = {Objective To study global gene expression profiles of early folliculogenesis
in primordial, primary, and secondary follicles.Design A cDNA microarray
study using amplified RNAs from isolated follicles.Setting Experimental
animal study.Animal(s) Female ICR strain mice (12 days old).Intervention(s)
Isolation of follicles at each stage, RNA isolation and amplification,
microarray hybridization, and statistical analysis for microarray.Main
Outcome Measure(s) Gene lists of various functional groups with an
estimated false discovery rate of 5%. Among them, platelet-derived
growth factors (PDGFs) and receptors were localized by immunohistochemistry
in mouse ovaries.Result(s) We analyzed a list of genes according
to function, such as apoptosis, cell cycle, cell proliferation and
maintenance, cytoskeleton, extracellular matrix, and signal transduction,
as well as according to frequency. Among the list of genes, we found
all PDGFs (A, B, C, and D) and receptors ([alpha] and [beta]) are
expressed with differential expression patterns in the oocytes and
ovarian cells according to stage of follicular development.Conclusion(s)
The present report suggests that genome-wide expression profiling
using microarray after RNA amplification may become a useful tool
to better understand the molecular mechanism(s) involved in early
ovarian folliculogenesis.},
issn = {0015-0282},
keywords = {Early follicular development, cDNA microarray, RNA amplification,
platelet-derived growth factor},
url = {http://www.sciencedirect.com/science/article/B6T6K-4J14DNY-18/2/c7645290363590d766d61c0ad459f9d0}
}
@ARTICLE{Yordanov2010,
author = {Yordanov, Yordan S. and Regan, Sharon and Busov, Victor},
title = {Members of the LATERAL ORGAN BOUNDARIES DOMAIN Transcription Factor
Family Are Involved in the Regulation of Secondary Growth in Populus},
journal = {PLANT CELL},
year = {2010},
volume = {22},
pages = {3662--3677},
number = {11},
month = nov,
abstract = {Regulation of secondary (woody) growth is of substantial economic
and environmental interest but is poorly understood. We identified
and subsequently characterized an activation-tagged poplar (Populus
tremula x Populus alba) mutant with enhanced woody growth and changes
in bark texture caused primarily by increased secondary phloem production.
Molecular characterization of the mutation through positioning of
the tag and retransformation experiments shows that the phenotype
is conditioned by activation of an uncharacterized gene that encodes
a novel member of the LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family
of transcription factors. Homology analysis showed highest similarity
to an uncharacterized LBD1 gene from Arabidopsis thaliana, and we
consequently named it Populus tremula x Populus alba (Pta) LBD1.
Dominant-negative suppression of Pta LBD1 via translational fusion
with the repressor SRDX domain caused decreased diameter growth and
suppressed and highly irregular phloem development. In wild-type
plants, LBD1 was most highly expressed in the phloem and cambial
zone. Two key Class I KNOTTED1-like homeobox genes that promote meristem
identity in the cambium were downregulated, while an Altered Phloem
Development gene that is known to promote phloem differentiation
was upregulated in the mutant. A set of four LBD genes, including
the LBD1 gene, was predominantly expressed in wood-forming tissues,
suggesting a broader regulatory role of these transcription factors
during secondary woody growth in poplar.},
comment = {10.1105/tpc.110.078634},
url = {http://www.plantcell.org/cgi/content/abstract/22/11/3662}
}
@ARTICLE{Yoshida2009,
author = {Yoshida, D. and Nomura, R. and Teramoto, A.},
title = {Signalling Pathway Mediated by CXCR7, an Alternative Chemokine Receptor
for Stromal-Cell Derived Factor-1α, in AtT20 Mouse Adrenocorticotrophic
Hormone-Secreting Pituitary Adenoma Cells},
journal = {Journal of Neuroendocrinology},
year = {2009},
volume = {21},
pages = {481--488},
number = {5},
abstract = {Stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, have
been identified in both neurones and glia of many brain areas. Previous
studies have mainly focused on the role of SDF-1 and CXCR4 in modulating
the hypothalamic-pituitary axis and their possible involvement in
the development of pituitary adenomas. An alternative SDF-1 receptor,
CXCR7, has recently been identified, but it has not been studied
in the context of pituitary adenomas. The present study aimed to
investigate the distribution and function of CXCR7 in pituitary adenomas.
The expression of CXCR7, normalised to β-actin, was assessed by
tissue microarray analysis of 62 adenomas, including 23 growth hormone
(GH)-producing adenomas, 22 nonfunctioning adenomas, seven prolactin
(PRL)-producing adenomas, six adrenocorticotrophic hormone-producing
adenomas and four thyroid-stimulating hormone-producing adenomas.
In vitro functional studies used RNA interference (RNAi) and cDNA
microarray analysis to evaluate the CXCR7 signalling pathway in AtT-20
mouse pituitary adenoma cells treated with recombinant mouse SDF-1α
and transfected with RNAi against Cxcr7 or control RNAi. In tissue
microarray analysis, prominent expression of CXCR7 was observed in
GH-producing adenomas and PRL-producing adenomas, and in macroadenomas
(PÂ <Â 0.05). Intracellular signalling via CXCR7 up-regulated Bub1,
Cdc29 and Ccnb1, and down-regulated Asns, Gpt, Pycr1, Cars and Dars.
The present study demonstrates that the SDF-1α/CXCR7 signalling
pathway regulates genes involved in cell cycle control, amino acid
metabolism and ligase activity, which comprise targets that are distinct
from those of CXCR4.},
issn = {1365-2826},
keywords = {CXCR4, CXCR7, intracellular signal, pituitary adenoma, SDF-1α},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2826.2009.01867.x}
}
@ARTICLE{Yoshida2011,
author = {Masa-aki Yoshida and Yukiko Ishikura and Takeya Moritaki and Eiichi
Shoguchi and Kentaro K. Shimizu and Jun Sese and Atsushi Ogura},
title = {Genome structure analysis of molluscs revealed whole genome duplication
and lineage specific repeat variation},
journal = {Gene},
year = {2011},
volume = {483},
pages = {63 - 71},
number = {1–2},
abstract = {Comparative genome structure analysis allows us to identify novel
genes, repetitive sequences and gene duplications. To explore lineage-specific
genomic changes of the molluscs that is good model for development
of nervous system in invertebrate, we conducted comparative genome
structure analyses of three molluscs, pygmy squid, nautilus and scallops
using partial genome shotgun sequencing. Most effective elements
on the genome structural changes are repetitive elements (REs) causing
expansion of genome size and whole genome duplication producing large
amount of novel functional genes. Therefore, we investigated variation
and proportion of REs and whole genome duplication. We, first, identified
variations of REs in the three molluscan genomes by homology-based
and de novo RE detection. Proportion of REs were 9.2%, 4.0%, and
3.8% in the pygmy squid, nautilus and scallop, respectively. We,
then, estimated genome size of the species as 2.1, 4.2 and 1.8 Gb,
respectively, with 2× coverage frequency and DNA sequencing theory.
We also performed a gene duplication assay based on coding genes,
and found that large-scale duplication events occurred after divergence
from the limpet Lottia, an out-group of the three molluscan species.
Comparison of all the results suggested that RE expansion did not
relate to the increase in genome size of nautilus. Despite close
relationships to nautilus, the squid has the largest portion of REs
and smaller genome size than nautilus. We also identified lineage-specific
RE and gene-family expansions, possibly relate to acquisition of
the most complicated eye and brain systems in the three species.},
doi = {10.1016/j.gene.2011.05.027},
issn = {0378-1119},
keywords = {Genome components},
url = {http://www.sciencedirect.com/science/article/pii/S0378111911002526}
}
@ARTICLE{Yoshida2007,
author = {Yoshida, Yasuko and Hachiya, Akira and Sriwiriyanont, Penkanok and
Ohuchi, Atsushi and Kitahara, Takashi and Takema, Yoshinori and Visscher,
Marty O. and Boissy, Raymond E.},
title = {Functional analysis of keratinocytes in skin color using a human
skin substitute model composed of cells derived from different skin
pigmentation types},
journal = {FASEB J},
year = {2007},
volume = {21},
pages = {2829--2839},
number = {11},
month = sep,
abstract = {Skin color is one of the most distinct features in the human race.
To assess the mechanisms of skin color variation, human skin substitutes
(HSS) were constructed by grafting mixtures of cultured keratinocytes
and melanocytes from a combination of donor skin types, together
with light skin derived fibroblasts, into chambers inserted onto
the back skin of severe combined immunodeficient (SCID) mice. The
resulting complexion coloration of the HSS was relatively darker
and lighter when dark and light skin derived keratinocytes, respectively,
were combined with melanocytes derived from either light or dark
skin. The melanin content in the epidermis and the maturation stage
of melanosomes in basal keratinocytes were significantly increased
in the HSS composed of dark compared to light skin derived keratinocytes.
In addition, the ratio of individual/clustered melanosomes in recipient
keratinocytes was increased in the former as opposed to the latter
HSS. The genetic expression of endothelin-1, proopiomelanocortin,
microphthalmia-associated transcription factor, tyrosinase, GP100,
and MART1 were increased in HSS composed of dark vs. light skin derived
keratinocytes. These data suggest that our HSS is a promising melanogenic
model that demonstrates the role of the keratinocyte in regulating
in part both melanogenesis and distribution of transferred melanosomes.--Yoshida,
Y., Hachiya, A., Sriwiriyanont, P., Ohuchi, A., Kitahara, T., Takema,
Y., Visscher, M. O., Boissy, R. E. Functional analysis of keratinocytes
in skin color using a human skin substitute model composed of cells
derived from different skin pigmentation types.},
url = {http://www.fasebj.org/cgi/content/abstract/21/11/2829}
}
@ARTICLE{Yoshihara2009,
author = {Yoshihara, Kosuke and Tajima, Atsushi and Komata, Dai and Yamamoto,
Tadashi and Kodama, Shoji and Fujiwara, Hiroyuki and Suzuki, Mitsuaki
and Onishi, Yoshitaka and Hatae, Masayuki and Sueyoshi, Kazunobu
and Fujiwara, Hisaya and Kudo, Yoshiki and Inoue, Ituro and Tanaka,
Kenichi},
title = {Gene expression profiling of advanced-stage serous ovarian cancers
distinguishes novel subclasses and implicates ZEB2 in tumor progression
and prognosis},
journal = {Cancer Science},
year = {2009},
volume = {100},
pages = {1421--1428},
number = {8},
abstract = {To elucidate the mechanisms of rapid progression of serous ovarian
cancer, gene expression profiles from 43 ovarian cancer tissues comprising
eight early stage and 35 advanced stage tissues were carried out
using oligonucleotide microarrays of 18Â 716 genes. By non-negative
matrix factorization analysis using 178 genes, which were extracted
as stage-specific genes, 35 advanced stage cases were classified
into two subclasses with superior (n = 17) and poor (n = 18)
outcome evaluated by progression-free survival (log rank test, PÂ =Â 0.03).
Of the 178 stage-specific genes, 112 genes were identified as showing
different expression between the two subclasses. Of the 48 genes
selected for biological function by gene ontology analysis or Ingenuity
Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2)
were extracted as candidates for prognostic factors associated with
progression-free survival. The relationship between high ZEB2 or
low CDH1 expression and shorter progression-free survival was validated
by real-time RT-PCR experiments of 37 independent advanced stage
cancer samples. ZEB2 expression was negatively correlated with CDH1
expression in advanced stage samples, whereas ZEB2 knockdown in ovarian
adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression.
Multivariate analysis showed that high ZEB2 expression was independently
associated with poor prognosis. Furthermore, the prognostic effect
of E-cadherin encoded by CDH1 was verified using immunohistochemical
analysis of an independent advanced stage cancer samples set (n = 74).
These findings suggest that the expression of epithelial–mesenchymal
transition-related genes such as ZEB2 and CDH1 may play important
roles in the invasion process of advanced stage serous ovarian cancer.
(Cancer Sci 2009)},
issn = {1349-7006},
publisher = {Blackwell Publishing Asia},
url = {http://dx.doi.org/10.1111/j.1349-7006.2009.01204.x}
}
@ARTICLE{Yoshii2011,
author = {Yukie Yoshii and Atsuo Waki and Kaori Yoshida and Anna Kakezuka and
Maki Kobayashi and Hideo Namiki and Yusei Kuroda and Yasushi Kiyono
and Hiroshi Yoshii and Takako Furukawa and Tatsuya Asai and Hidehiko
Okazawa and Juri G. Gelovani and Yasuhisa Fujibayashi},
title = {The use of nanoimprinted scaffolds as 3D culture models to facilitate
spontaneous tumor cell migration and well-regulated spheroid formation},
journal = {Biomaterials},
year = {2011},
volume = {32},
pages = {6052 - 6058},
number = {26},
abstract = {Two-dimensional (2D) cell cultures are essential for drug development
and tumor research. However, the limitations of 2D cultures are widely
recognized, and a better technique is needed. Recent studies have
indicated that a strong physical contact between cells and 2D substrates
induces cellular characteristics that differ from those of tumors
growing in vivo. 3D cell cultures using various substrates are then
developing; nevertheless, conventional approaches have failed in
maintenance of cellular proliferation and viability, uniformity,
reproducibility, and/or simplicity of these assays. Here, we developed
a 3D culture system with inorganic nanoscale scaffolding using nanoimprinting
technology (nano-culture plates), which reproduced the characteristics
of tumor cells growing in vivo. Diminished cell-to-substrate physical
contact facilitated spontaneous tumor cell migration, intercellular
adhesion, and multi-cellular 3D-spheroid formation while maintaining
cellular proliferation and viability. The resulting multi-cellular
spheroids formed hypoxic core regions similar to tumors growing in vivo.
This technology allows creating uniform and highly-reproducible 3D
cultures, which is easily applicable for microscopic and spectrophotometric
assays, which can be used for high-throughput/high-content screening
of anticancer drugs and should accelerate discovery of more effective
anticancer therapies.},
doi = {10.1016/j.biomaterials.2011.04.076},
issn = {0142-9612},
keywords = {Hypoxia},
url = {http://www.sciencedirect.com/science/article/pii/S0142961211004984}
}
@ARTICLE{Yoshikawa2004,
author = {Yoshikawa, Masanobu and Kobayashi, Tomomi and Oka, Tetsuo and Kawaguchi,
Mitsuru and Hashimoto, Atsushi},
title = {Distribution and MK-801-induced expression of serine racemase mRNA
in rat brain by real-time quantitative PCR},
journal = {Molecular Brain Research},
year = {2004},
volume = {128},
pages = {90--94},
number = {1},
month = sep,
abstract = {We have used real-time quantitative PCR methods to evaluate the effect
of the systemic administration of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
(MK-801; 0.4 mg/kg) on the gene expression of serine racemase in
several brain areas of the rat. The levels of serine racemase mRNA
in all the brain areas transiently increased after the administration.
The present findings suggest that there is a link between the expression
of serine racemase mRNA and the activity of the NMDA receptors.},
issn = {0169-328X},
keywords = {D-Amino acid oxidase, Glycine site, N-Methyl-D-aspartate receptor,
Real-time quantitative PCR, D-Serine, Serine racemase},
url = {http://www.sciencedirect.com/science/article/B6T07-4CXMYJ2-2/2/42cbbe33bf0e9fb530ffba5e3f781b9e}
}
@ARTICLE{Yoshikawa2004a,
author = {Yoshikawa, Mamoru and Nakajima, Toshiharu and Matsumoto, Kenji and
Okada, Naoko and Tsukidate, Toshiharu and Iida, Makoto and Otori,
Nobuyoshi and Haruna, Shin-ichi and Moriyama, Hiroshi and Imai, Toshio
and Saito, Hirohisa},
title = {TNF-[alpha] and IL-4 regulate expression of fractalkine (CX3CL1)
as a membrane-anchored proadhesive protein and soluble chemotactic
peptide on human fibroblasts},
journal = {FEBS Letters},
year = {2004},
volume = {561},
pages = {105--110},
number = {1-3},
month = mar,
abstract = {The CX3C chemokine, fractalkine (FKN, CX3CL1), has multiple functions
and exists as two distinct forms, a membrane-anchored protein and
a soluble chemotactic peptide that cleaves from the cell surface
FKN. In this study, we first demonstrated the expression of FKN in
tumor necrosis factor (TNF)-[alpha]- and interleukin (IL)-4-stimulated
human fibroblasts. The induction of FKN was observed for both forms.
We also demonstrated monocyte chemotactic activity in the culture
supernatant from the fibroblasts stimulated with these cytokines.
These results suggest that TNF-[alpha]- and IL-4-stimulated fibroblasts
may play an important role in accumulation of monocytes at inflammatory
sites.},
issn = {0014-5793},
keywords = {Fractalkine, CX3CL1, Tumor necrosis factor-[alpha], Interleukin-4,
Fibroblast},
url = {http://www.sciencedirect.com/science/article/B6T36-4BVPCF7-5/2/1d64fe6db56a339ddcfaddb149a3d31d}
}
@ARTICLE{Yoshikawa2003,
author = {Yoshikawa, Mamoru and Nakajima, Toshiharu and Tsukidate, Toshiharu
and Matsumoto, Kenji and Iida, Makoto and Otori, Nobuyoshi and Haruna,
Shin-ichi and Moriyama, Hiroshi and Saito, Hirohisa},
title = {TNF-[alpha] and IL-4 regulate expression of IL-13 receptor [alpha]2
on human fibroblasts},
journal = {Biochemical and Biophysical Research Communications},
year = {2003},
volume = {312},
pages = {1248--1255},
number = {4},
month = dec,
abstract = {Two interleukin 13 receptors (IL-13Rs) have been identified as IL-13R[alpha]1
and IL-13R[alpha]2. IL-13R[alpha]1 is composed of a heterodimer consisting
of IL-13R[alpha]1 and IL-4 receptor [alpha] (IL-4R[alpha]) as a signaling
subunit. In contrast, IL-13R[alpha]2 is known as a decoy receptor
for IL-13. In this study, we investigated the expression of IL-13Rs
on human fibroblasts. IL-13R[alpha]2 was significantly up-regulated
after stimulation with tumor necrosis factor-[alpha] (TNF-[alpha])
and/or IL-4. In contrast, IL-13R[alpha]1 was constitutively detectable
and was not up-regulated. After the induction of IL-13[alpha]2 by
IL-4, STAT6 phosphorylation through IL-13R[alpha]1 by IL-13 was inhibited.
We also detected large intracellular pools of IL-13R[alpha]2 in fibroblasts
quantitatively. Furthermore, mobilization of the IL-13R[alpha]2 protein
stores from the cytoplasm to the cell surface was prevented by an
inhibitor of protein transport, brefeldin-A. These results indicate
that TNF-[alpha] and IL-4 synergistically up-regulate the expression
of IL-13R[alpha]2 decoy receptor on human fibroblasts by inducing
gene expression and mobilizing intracellular receptors, and thus
may down-regulate the IL-13 signaling.},
issn = {0006-291X},
keywords = {IL-13R[alpha]2, Decoy receptor, Human fibroblast, TNF-[alpha], IL-4,
Mobilization},
url = {http://www.sciencedirect.com/science/article/B6WBK-4B3JS9Y-S/2/12c2ffebc7fdddb679c6851171e4035d}
}
@ARTICLE{Yoshikawa2004b,
author = {Yoshikawa, Masanobu and Oka, Tetsuo and Kawaguchi, Mitsuru and Hashimoto,
Atsushi},
title = {MK-801 upregulates the expression of D-amino acid oxidase mRNA in
rat brain},
journal = {Molecular Brain Research},
year = {2004},
volume = {131},
pages = {141--144},
number = {1-2},
month = nov,
abstract = {We have evaluated the effect of the systemic administration of MK-801
(0.4 mg/kg) on the gene expression of D-amino acid oxidase (DAO)
in several brain areas of the rat. The levels of DAO mRNA in all
the brain areas significantly increased and peaked at 4 h after the
administration. The present results suggest that there is a link
between the expression of DAO mRNA and the N-methyl-D-aspartate (NMDA)
receptor activity.},
issn = {0169-328X},
keywords = {D-Amino acid oxidase, N-Methyl-D-aspartate receptor, Real-time quantitative
PCR, Schizophrenia, D-Serine, Serine racemase},
url = {http://www.sciencedirect.com/science/article/B6T07-4DD8X0Y-2/2/24a68198e02edac66b4427cbfc967924}
}
@ARTICLE{Yoshimoto2008,
author = {Yoshimoto, Koji and Dang, Julie and Zhu, Shaojun and Nathanson, David
and Huang, Tiffany and Dumont, Rebecca and Seligson, David B. and
Yong, William H. and Xiong, Zhenggang and Rao, Nagesh and Winther,
Henrik and Chakravarti, Arnab and Bigner, Darell D. and Mellinghoff,
Ingo K. and Horvath, Steve and Cavenee, Webster K. and Cloughesy,
Timothy F. and Mischel, Paul S.},
title = {Development of a Real-time RT-PCR Assay for Detecting EGFRvIII in
Glioblastoma Samples},
journal = {Clin. Cancer Res.},
year = {2008},
volume = {14},
pages = {488--493},
number = {2},
month = jan,
abstract = {Purpose: Epidermal growth factor receptor variant III (EGFRvIII) is
an oncogenic, constitutively active mutant form of the EGFR that
is commonly expressed in glioblastoma and is also detected in a number
of epithelial cancers. EGFRvIII presents a unique antigenic target
for anti-EGFRvIII vaccines and it has been shown to modulate response
to EGFR kinase inhibitor therapy. Thus, detection in clinical samples
may be warranted. Existing patents preclude the use of anti-EGFRvIII
antibodies for clinical detection. Further, frozen tissue is not
routinely available, particularly for patients treated in the community.
Thus, detection of EGFRvIII in formalin-fixed paraffin-embedded (FFPE)
clinical samples is a major challenge. Experimental Design: We developed
a real-time reverse transcription-PCR (RT-PCR) assay for detecting
EGFRvIII in FFPE samples and analyzed 59 FFPE glioblastoma clinical
samples with paired frozen tissue from the same surgical resection.
We assessed EGFRvIII protein expression by immunohistochemistry using
two distinct specific anti-EGFRvIII antibodies and examined EGFR
gene amplification by fluorescence in situ hybridization. Results:
The FFPE RT-PCR assay detected EGFRvIII in 16 of 59 (27%) samples,
exclusively in cases with EGFR amplification, consistent with the
expected frequency of this alteration. The FFPE RT-PCR assay was
more sensitive and specific for detecting EGFRvIII than either of
the two antibodies alone, or in combination, with a sensitivity of
93% (95% confidence interval, 0.78-1.00) and a specificity of 98%
(95% confidence interval, 0.93-1.00). Conclusion: This assay will
facilitate accurate assessment of EGFRvIII in clinical samples and
may aid in the development of strategies for stratifying patients
for EGFRvIII-directed therapies.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/14/2/488}
}
@ARTICLE{Yoshimoto2009,
author = {Yoshimoto, Maisa and Graham, Cassandra and Chilton-MacNeill, Susan
and Lee, Eric and Shago, Mary and Squire, Jeremy and Zielenska, Maria
and Somers, Gino R.},
title = {Detailed cytogenetic and array analysis of pediatric primitive sarcomas
reveals a recurrent CIC-DUX4 fusion gene event},
journal = {Cancer Genetics and Cytogenetics},
year = {2009},
volume = {195},
pages = {1--11},
number = {1},
month = nov,
abstract = {Pediatric undifferentiated soft tissue sarcomas (USTS) are a diagnostically
challenging group of neoplasms. Recently, a subcategory of USTS with
primitive round cell morphology and a t(4;19)(q35;q13) rearrangement
has been defined. The present study applied high-throughput array
comparative genomic hybridization together with spectral karyotyping,
four-color fluorescence in situ hybridization (FISH), and reverse
transcriptase-polymerase chain reaction (RT-PCR) to a series of three
pediatric USTS. Two of these had primitive round cell morphology
with CD99 positivity; the third had a spindled and myxoid appearance.
By genomic analyses, both primitive round cell sarcomas had t(4;19)(q13;q35)
rearrangements in addition to several imbalances throughout the genome.
Four-color FISH and in silico analyses of the breakpoint region at
19q13 identified the potential involvement of the candidate oncogene
CIC. By RT-PCR, fusion transcripts involving CIC (19q13) and DUX4
(4q35) were confirmed to be present in both primitive round cell
sarcomas, further defining the breakpoints seen by genomic analysis.
Described here are two tumors belonging to the rare category of CIC-DUX4-positive
primitive sarcomas, with detailed cytogenetic and genomic information
regarding this novel subclass of pediatric malignancy. Molecular
and cytogenetic techniques for the detection of the CIC-DUX4 fusion
gene are described, to aid in recognition and diagnosis.},
issn = {0165-4608},
url = {http://www.sciencedirect.com/science/article/B6T53-4XG52GG-3/2/398e3dd3cfeed3eb6a2ede569baf8368}
}
@ARTICLE{Yoshimoto2007,
author = {Yoshimoto, T and Matsuura, K and Karnan, S and Tagawa, H and Nakada,
C and Tanigawa, M and Tsukamoto, Y and Uchida, T and Kashima, K and
Akizuki, S and Takeuchi, I and Sato, F and Mimata, H and Seto, M
and Moriyama, M},
title = {High-resolution analysis of DNA copy number alterations and gene
expression in renal clear cell carcinoma},
journal = {J. Pathol.},
year = {2007},
volume = {213},
pages = {392--401},
number = {4},
abstract = {Abstract 10.1002/path.2239.abs We analysed chromosomal copy number
aberrations (CNAs) in renal cell carcinomas by array-based comparative
genomic hybridization, using a genome-wide scanning array with 2304
BAC and PAC clones covering the whole human genome at a resolution
of roughly 1.3 Mb. A total of 30 samples of renal cell carcinoma
were analysed, including 26 cases of clear cell carcinoma (CCC) and
four cases of chromophobe renal cell carcinoma (ChCC). In CCCs, gains
of chromosomes 5q33.1-qter (58%), 7q11.22-q35 (35%) and 16p12.3-p13.12
(19%), and losses of chromosomes 3p25.1-p25.3 (77%), 3p21.31-p22.3
(81%), 3p14.1-p14.2 (77%), 8p23.3 (31%), 9q21.13-qter (19%) and 14q32.32-qter
(38%) were detected. On the other hand, the patterns of CNAs differed
markedly between CCCs and ChCCs. Next, we examined the correlation
of CNAs with expression profiles in the same tumour samples in 22/26
cases of CCC, using oligonucleotide microarray. We extracted genes
that were differentially expressed between cases with and without
CNAs, and found that significantly more up-regulated genes were localized
on chromosomes 5 and 7, where recurrent genomic gains have been detected.
Conversely, significantly more down-regulated genes were localized
on chromosomes 14 and 3, where recurrent genomic losses have been
detected. These results revealed that CNAs were correlated with deregulation
of gene expression in CCCs. Furthermore, we compared the patterns
of genomic imbalance with histopathological features, and found that
loss of 14q appeared to be a specific and additional genetic abnormality
in high-grade CCC. When we compared the expression profiles of low-grade
CCCs with those of high-grade CCCs, differentially down-regulated
genes tended to be localized on chromosomes 14 and 9. Thus, it is
suggested that copy number loss at 14q in high-grade CCC may be involved
in the down-regulation of genes located in this region. Copyright
© 2007 Pathological Society of Great Britain and Ireland. Published
by John Wiley & Sons, Ltd.},
issn = {1096-9896},
keywords = {renal cell carcinoma, clear cell carcinoma, array CGH, gene expression,
oligonucleotide microarray},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/path.2239}
}
@ARTICLE{Yoshimura2008,
author = {Yoshimura, Hiromitsu and Ito, Masayoshi and Kuwahara, Yusuke and
Ishii, Aiko and Tsuritani, Katsuki and Nakamura, Atsushi and Hirasawa,
Yasushi and Nagamatsu, Tadashi},
title = {Downregulated expression in high IgA (HIGA) mice and the renal protective
role of meprin[beta]},
journal = {Life Sciences},
year = {2008},
volume = {82},
pages = {899--908},
number = {15-16},
month = apr,
abstract = {This study discusses the critical role of the metalloproteinase meprin[beta]
in the progression of glomerulonephritis. Using a microarray technique,
the gene expression profiles in glomeruli isolated from high serum
IgA (HIGA) mice with a purity of 97% or greater were examined. HIGA
mice are a valid model of human IgA nephropathy (IgAN), with the
typical pathological features of this condition, including a consistently
high serum IgA level as well as dominant mesangial IgA deposition
and mesangial enlargement. Among the many upregulated/downregulated
genes after the development of IgAN, the downregulation of meprin[beta]
was intriguing. The expression level of the meprin[beta] gene at
40 weeks of age was 52% of that observed at 8 weeks of age (prior
to the development of IgAN), although in the control BALB/c mice,
a 2.19-fold elevation was seen. These results were also confirmed
by semi-quantitative RT-PCR and immunostaining analyses. As meprin[beta]
is a subunit of metalloproteinase meprins (meprin A, meprin B) and
meprins are capable of proteolytically degrading extracellular matrix
(ECM) components and proteolytically processing bioactive peptides,
the downregulation of meprin[beta] may contribute to the progression
of glomerulonephritis and the eventual glomerular scarring. This
working hypothesis was examined using an in vivo meprin[beta] inhibition
study. The inhibition of meprins by actinonin exacerbated some parameters
of renal injury in mice afflicted with anti-glomerular basement membrane
(anti-GBM) antibody-associated nephritis. These in vitro and in vivo
results suggest that meprin[beta] may play a protective role against
the progression of renal injury through the degradation of ECM and
bioactive peptides.},
issn = {0024-3205},
keywords = {cDNA microarray, Meprin[beta], HIGA mice, IgA nephropathy, Extracellular
matrix, Anti-GBM antibody-associated nephritis},
url = {http://www.sciencedirect.com/science/article/B6T99-4RX07B4-2/2/8dc733fb64c0ba5166956dffdcf4fc7f}
}
@ARTICLE{Yoshimura2009,
author = {Yoshimura, Hiromitsu and Sakai, Takayuki and Kuwahara, Yusuke and
Ito, Masayoshi and Tsuritani, Katsuki and Hirasawa, Yasushi and Nagamatsu,
Tadashi},
title = {Effects of kynurenine metabolites on mesangial cell proliferation
and gene expression},
journal = {Experimental and Molecular Pathology},
year = {2009},
volume = {87},
pages = {70--75},
number = {1},
month = aug,
abstract = {In the present study, we examined the effects of kynurenine metabolites
on cultured mesangial cells (MCs) and demonstrated for the first
time that they affect MC proliferation and gene expression. Anthranilic
acid and 3-hydroxy-dl-kynurenine suppressed MC proliferation by 32%
and 43%, respectively at 10- 6 M compared to the control. In contrast,
quinolinic acid and l-kynurenine promoted MC proliferation by 49%
and 35% at 10- 8 M respectively, although promoting activities declined
at higher concentrations. In addition, quinolinic acid upregulated
the gene expression of platelet-derived growth factor-B, collagen
type-I[alpha]1, and collagen type-IV[alpha]1. However, the gene expression
of hepatocyte growth factor (HGF) was downregulated. We further examined
the gene expressions in the glomeruli of high serum IgA (HIGA) mice
with IgA nephropathy using microarray technology and found that the
gene expression of insulin-like growth factor-1 was higher, but that
of HGF was lower at 40 weeks of age compared to 8 weeks of age. In
Balb/c mice, the gene expression of three kynurenine pathway enzymes
(kynurenine aminotransferase I, kynurenine aminotransferase II, and
quinolinate phospho-ribosyltransferase) increased 2- to 3.5-fold,
whereas those in HIGA mice did not change significantly. These results
suggest that abnormalities in the kynurenine pathway are associated
with the dysfunction of MCs and progression of chronic kidney diseases.},
issn = {0014-4800},
keywords = {Kynurenine metabolites, Chronic renal diseases, Mesangial cell, Microarray
technology, HIGA mice},
url = {http://www.sciencedirect.com/science/article/B6WFB-4VRP289-1/2/7c8f685f984f4e394f48e90ea037c1ef}
}
@ARTICLE{Yoshino2011,
author = {Yoshino, H and Chiyomaru, T and Enokida, H and Kawakami, K and Tatarano,
S and Nishiyama, K and Nohata, N and Seki, N and Nakagawa, M},
title = {The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2
in bladder cancer},
journal = {Br J Cancer},
year = {2011},
volume = {104},
pages = {808--818},
number = {5},
month = mar,
issn = {0007-0920},
publisher = {Cancer Research UK},
url = {http://dx.doi.org/10.1038/bjc.2011.23}
}
@ARTICLE{Yoshino2012,
author = {Hirofumi Yoshino and Hideki Enokida and Takeshi Chiyomaru and Shuichi
Tatarano and Hideo Hidaka and Takeshi Yamasaki and Takenari Gotannda
and Tokushi Tachiwada and Nijiro Nohata and Takashi Yamane and Naohiko
Seki and Masayuki Nakagawa},
title = {Tumor suppressive microRNA-1 mediated novel apoptosis pathways through
direct inhibition of splicing factor serine/arginine-rich 9 (SRSF9/SRp30c)
in bladder cancer},
journal = {Biochemical and Biophysical Research Communications},
year = {2012},
volume = {417},
pages = {588 - 593},
number = {1},
abstract = {We have previously found that restoration of tumor suppressive microRNA-1
(miR-1), induced cell apoptosis in bladder cancer (BC) cell lines.
However, the apoptosis mechanism induced by miR-1 was not fully elucidated.
Alternative splicing of mRNA precursors provides cancer cells with
opportunities to translate many oncogenic protein variants, which
promote cell proliferation and survival under unpreferable condition
for cancer development. Serine/arginine-rich (SR) protein family,
which involved in alternative pre-mRNA splicing, plays a critical
role for regulating apoptosis by splicing apoptosis-related genes.
However, transcriptional regulation of SR proteins, themselves, has
not been elucidated. In this study, we focused on splicing factor
serine/arginine-rich 9 (SRSF9/SRp30c) on the basis of our previous
genome-wide gene expression analysis using miR-1-transfected BC cell
lines because putative target sites of miR-1 are existed in 3′-untranslated
region (UTR) of SRSF9 mRNA. The expression levels of mRNA of SRSF9
were extremely reduced in the miR-1 transfectants. A luciferase activity
significantly decreased in the transfectants suggesting that actual
binding occurred between miR-1 and 3′UTR of SRSF9 mRNA. Loss-of-function
assays demonstrated that significant inhibitions of cell proliferation,
migration, and invasion were observed in the si-SRSF9 transfectants.
Apoptosis assays demonstrated that cell apoptosis fraction increased
and that caspase-3/7 was activated in the si-SRSF9 transfectants.
Our data indicated that tumor suppressive miR-1 induces apoptosis
through direct inhibition of SRSF9 in BC. The identification of molecular
mechanisms between miRNAs and SR proteins could provide novel apoptosis
pathways and their epigenetic regulations and offer new strategies
for BC treatment.},
doi = {10.1016/j.bbrc.2011.12.011},
issn = {0006-291X},
keywords = {SRSF9/SRp30c},
url = {http://www.sciencedirect.com/science/article/pii/S0006291X11022133}
}
@ARTICLE{You2011,
author = {You, Frank and Huo, Naxin and Deal, Karin and Gu, Yong and Luo, Ming-Cheng
and McGuire, Patrick and Dvorak, Jan and Anderson, Olin},
title = {Annotation-based genome-wide SNP discovery in the large and complex
Aegilops tauschii genome using next-generation sequencing without
a reference genome sequence},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {59},
number = {1},
abstract = {BACKGROUND:Many plants have large and complex genomes with an abundance
of repeated sequences. Many plants are also polyploid. Both of these
attributes typify the genome architecture in the tribe Triticeae,
whose members include economically important wheat, rye and barley.
Large genome sizes, an abundance of repeated sequences, and polyploidy
present challenges to genome-wide SNP discovery using next-generation
sequencing (NGS) of total genomic DNA by making alignment and clustering
of short reads generated by the NGS platforms difficult, particularly
in the absence of a reference genome sequence.RESULTS:An annotation-based,
genome-wide SNP discovery pipeline is reported using NGS data for
large and complex genomes without a reference genome sequence. Roche
454 shotgun reads with low genome coverage of one genotype are annotated
in order to distinguish single-copy sequences and repeat junctions
from repetitive sequences and sequences shared by paralogous genes.
Multiple genome equivalents of shotgun reads of another genotype
generated with SOLiD or Solexa are then mapped to the annotated Roche
454 reads to identify putative SNPs. A pipeline program package,
AGSNP, was developed and used for genome-wide SNP discovery in Aegilops
tauschii-the diploid source of the wheat D genome, and with a genome
size of 4.02 Gb, of which 90% is repetitive sequences. Genomic DNA
of Ae. tauschii accession AL8/78 was sequenced with the Roche 454
NGS platform. Genomic DNA and cDNA of Ae. tauschii accession AS75
was sequenced primarily with SOLiD, although some Solexa and Roche
454 genomic sequences were also generated. A total of 195,631 putative
SNPs were discovered in gene sequences, 155,580 putative SNPs were
discovered in uncharacterized single-copy regions, and another 145,907
putative SNPs were discovered in repeat junctions. These SNPs were
dispersed across the entire Ae. tauschii genome. To assess the false
positive SNP discovery rate, DNA containing putative SNPs was amplified
by PCR from AL8/78 and AS75 and resequenced with the ABI 3730 xl.
In a sample of 302 randomly selected putative SNPs, 84.0% in gene
regions, 88.0% in repeat junctions, and 81.3% in uncharacterized
regions were validated.CONCLUSION:An annotation-based genome-wide
SNP discovery pipeline for NGS platforms was developed. The pipeline
is suitable for SNP discovery in genomic libraries of complex genomes
and does not require a reference genome sequence. The pipeline is
applicable to all current NGS platforms, provided that at least one
such platform generates relatively long reads. The pipeline package,
AGSNP, and the discovered 497,118 Ae. tauschii SNPs can be accessed
at (http://avena.pw.usda.gov/wheatD/agsnp.shtml).},
doi = {10.1186/1471-2164-12-59},
issn = {1471-2164},
pubmedid = {21266061},
url = {http://www.biomedcentral.com/1471-2164/12/59}
}
@ARTICLE{You2009,
author = {You, Hong and Zhang, Wenbao and Moertel, Luke and McManus, Donald
P. and Gobert, Geoffrey N.},
title = {Transcriptional profiles of adult male and female Schistosoma japonicum
in response to insulin reveal increased expression of genes involved
in growth and development},
journal = {International Journal for Parasitology},
year = {2009},
volume = {39},
pages = {1551--1559},
number = {14},
month = dec,
abstract = {Microarray analysis was used to investigate differential gene regulation
in adult male and female Schistosoma japonicum cultured in the presence
or absence of insulin in vitro. A total of 1,101 genes were up- or
down-regulated in response to insulin, the majority of differential
expression occurring 24 h after the addition of insulin to the cultures.
Genes differentially expressed in male or female worms were predominantly
involved in growth and development, with significant sex-specific
differences in transcriptional profiles evident. Insulin appeared
to promote protein synthesis and control protein degradation more
prominently in male parasites. The study also indicated that insulin
plays a more pronounced role in the uptake of glucose in unpaired
female parasites, as reflected in the increased stimulation of gene
expression of the phosphatidylinositol 3-kinase sub-pathway of insulin
signalling. Insulin may also impact on the sexual differentiation
and fecundity of female schistosomes by activation of the mitogenic-activated
protein kinase sub-pathway.},
issn = {0020-7519},
keywords = {Microarray, Schistosoma japonicum, Gene expression, Insulin},
url = {http://www.sciencedirect.com/science/article/B6T7F-4WRD3N5-1/2/9ec5f774042528e91d791fb550f18b2b}
}
@ARTICLE{You2008,
author = {You, Qiumei and Karrow, Niel A. and Cao, Honghe and Rodriguez, Alexander
and Mallard, Bonnie A. and Boermans, Herman J.},
title = {Variation in the ovine cortisol response to systemic bacterial endotoxin
challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal
axis},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {230},
pages = {1--8},
number = {1},
month = jul,
abstract = {Bi-directional communication between the neuroendocrine and immune
systems is designed, in part, to maintain or restore homeostasis
during physiological stress. Exposure to endotoxin during Gram-negative
bacterial infection for example, elicits the release of pro-inflammatory
cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA).
The secretion of adrenal glucocorticoids subsequently down regulates
the host inflammatory response, minimizing potential tissue damage.
Sequence and epigenetic variants in genes involved in regulating
the neuroendocrine and immune systems are likely to contribute to
individual differences in the HPAA response, and this may influence
the host anti-inflammatory response to toxin exposure and susceptibility
to inflammatory disease. In this study, high (HCR) and low (LCR)
cortisol responders were selected from a normal population of 110
female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg)
to identify potential determinants that contribute to variation in
the cortisol response phenotype. This phenotype was stable over several
years in the HCR and LCR animals, and did not appear to be attributed
to differences in expression of hepatic immune-related genes or systemic
pro-inflammatory cytokine concentrations. Mechanistic studies using
corticotrophin-releasing factor (0.5 [mu]g/kg body weight), arginine
vasopressin (0.5 [mu]g/kg), and adrenocorticotropic hormone (0.5 [mu]g/kg)
administered iv demonstrated that variation in this phenotype is
largely determined by signalling within the HPAA. Future studies
will use this ovine HCR/LCR model to investigate potential genetic
and epigenetic variants that may contribute to variation in cortisol
responsiveness to bacterial endotoxin.},
issn = {0041-008X},
keywords = {Endotoxin, Variation in cortisol response, Hepatic gene expression,
Pro-inflammatory cytokines, CRF, AVP, ACTH},
url = {http://www.sciencedirect.com/science/article/B6WXH-4RTM2TY-2/2/c0896d2be8957afb6e2b727f434273f7}
}
@ARTICLE{You2006,
author = {You, Young-Sook and Marella, Heather and Zentella, Rodolfo and Zhou,
Yiyong and Ulmasov, Tim and Ho, Tuan-Hua David and Quatrano, Ralph
S.},
title = {Use of Bacterial Quorum-Sensing Components to Regulate Gene Expression
in Plants},
journal = {Plant Physiology},
year = {2006},
volume = {140},
pages = {1205--1212},
number = {4},
month = apr,
abstract = {We describe an efficient inducible system to regulate gene expression
in plants based on quorum-sensing components found in Gram-negative
bacteria such as Agrobacterium tumefaciens. These bacteria monitor
their own population density by utilizing members of the N-acyl homoserine
lactone family as inducers and a transcriptional activator as its
receptor. In our study, we utilize the components from A. tumefaciens
(i.e. 3-oxooctanyl-L-homoserine lactone [OOHL]) synthesized by the
TraI protein and its receptor, TraR. When OOHL binds to TraR, it
recognizes its specific cis-element, the tra box. We translationally
fused the eukaryotic VP16 activation domain to the N terminus of
TraR. In the presence of OOHL, the chimeric VP16:TraR transcriptional
regulator induces reporter gene expression in moss (Physcomitrella
patens), barley (Hordeum vulgare), and carrot (Daucus carota) cells,
as well as in transgenic Arabidopsis (Arabidopsis thaliana) seedlings.
The inducible system shows a low level of reporter gene expression
in the absence of the inducer. Foliar application and a floating-leaf
assay in the presence of the inducer shows a 30- and 200-fold induction,
respectively. Induction by foliar application of the inducer to whole
seedlings is achieved within 8 h. The VP16:TraR activator also shows
specificity for binding to its cognate inducer, OOHL. Based on microarray
analyses, endogenous gene expression is not significantly affected
due to overexpression of the TraR protein or presence of OOHL in
either wild-type or lactone-inducible transgenic plants.},
url = {http://www.plantphysiol.org/cgi/content/abstract/140/4/1205}
}
@ARTICLE{Young2010,
author = {Young, Amber and Assey, Kristin S. and Sturkie, Carla D. and West,
Franklin D. and Machacek, David W. and Stice, Steven L.},
title = {Glial cell line-derived neurotrophic factor enhances in vitro differentiation
of mid-/hindbrain neural progenitor cells to dopaminergic-like neurons},
journal = {J. Neurosci. Res.},
year = {2010},
volume = {88},
pages = {3222--3232},
number = {15},
abstract = {Abstract Parkinson's disease (PD) affects the motor system through
the degeneration of the dopaminergic neurons of the substantia nigra.
The use of human embryonic stem cell (hESC)-derived human neural
progenitor (hNP) cells provides a potential cell source for cell
therapies and drug screens for future treatments. Glial cell line-derived
neurotrophic factor (GDNF) is a known dopaminergic neuroprotectant
agent; however, its potential role in neural differentiation remains
largely unknown. Addition of 25 ng/ml GDNF to hNP cell differentiation
media, over a 21-day period, induced a significantly (P < 0.05) greater
portion of hNP cells to differentiate into dopaminergic neurons than
non-GDNF cultures, 50% compared with 2.9% of cells expressing tyrosine
hydroxylase (TH), respectively. The hNP cells exposed to GDNF selectively
expressed dopamine receptors 1, 4, and 5 and were evoked to release
dopamine with KCl. This is the first report of GDNF and leukemia
inhibitory factor enriching hESC-derived hNP cells toward dopaminergic-like
neurons. © 2010 Wiley-Liss, Inc.},
issn = {1097-4547},
keywords = {Parkinson's disease, human embryonic stem cells, dopaminergic development,
neural progenitor cells},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/jnr.22499}
}
@ARTICLE{Young2011,
author = {A. Young and D.W. Machacek and S.K. Dhara and P.R. MacLeish and M.
Benveniste and M.C. Dodla and C.D. Sturkie and S.L. Stice},
title = {Ion channels and ionotropic receptors in human embryonic stem cell
derived neural progenitors},
journal = {Neuroscience},
year = {2011},
volume = {192},
pages = {793 - 805},
number = {0},
abstract = {Human neural progenitor cells differentiated from human embryonic
stem cells offer a potential cell source for studying neurodegenerative
diseases and for drug screening assays. Previously, we demonstrated
that human neural progenitors could be maintained in a proliferative
state with the addition of leukemia inhibitory factor and basic fibroblast
growth factor. Here we demonstrate that 96 h after removal of basic
fibroblast growth factor the neural progenitor cell culture was significantly
altered and cell replication halted. Fourteen days after the removal
of basic fibroblast growth factor, most cells expressed microtubule-associated
protein 2 and TUJ1, markers characterizing a post-mitotic neuronal
phenotype as well as neural developmental markers Cdh2 and Gbx2.
Real-time PCR was performed to determine the ionotropic receptor
subunit expression profile. Differentiated neural progenitors express
subunits of glutamatergic, GABAergic, nicotinic, purinergic and transient
receptor potential receptors. In addition, sodium and calcium channel
subunits were also expressed. Functionally, virtually all the hNP
cells tested under whole-cell voltage clamp exhibited delayed rectifier
potassium channel currents and some differentiated cells exhibited
tetrodotoxin-sensitive, voltage-dependent sodium channel current.
Action potentials could also be elicited by currents injection under
whole-cell current clamp in a minority of cells. These results indicate
that removing basic fibroblast growth factor from the neural progenitor
cell cultures leads to a post-mitotic state, and has the capability
to produce excitable cells that can generate action potentials, a
landmark characteristic of a neuronal phenotype. This is the first
report of an efficient and simple means of generating human neuronal
cells for ionotropic receptor assays and ultimately for electrically
active human neural cell assays for drug discovery.},
doi = {10.1016/j.neuroscience.2011.04.039},
issn = {0306-4522},
keywords = {human embryonic stem cells},
url = {http://www.sciencedirect.com/science/article/pii/S030645221100457X}
}
@ARTICLE{Young2005,
author = {Young, Pampee P. and Modur, Vijay and Teleron, Amylynn A. and Ladenson,
Jack H.},
title = {Enrichment of Genes in the Aortic Intima That Are Associated With
Stratified Epithelium: Implications of Underlying Biomechanical and
Barrier Properties of the Arterial Intima},
journal = {Circulation},
year = {2005},
volume = {111},
pages = {2382--2390},
number = {18},
month = may,
abstract = {Background-- Arteries and veins are exposed to different pressures
and are easily distinguished by morphology. Although several recent
studies have focused on differential gene expression between the
arterial and venous endothelium, the molecular distinctions that
give rise to the dramatic structural distinctions between arteries
and veins, such as in the organization of the intima, are not known.
Methods and Results-- We used high-density oligonucleotide arrays
to analyze the transcriptional profile of the mouse aorta and inferior
vena cava (IVC), not restricting our analysis to the endothelium,
to identify genes whose expression was enriched in aorta over other
tissues and the IVC. By quantitative reverse transcription-polymerase
chain reaction analysis, these genes have been shown to be highly
expressed in the mouse aorta and were either expressed at low levels
or were undetectable in the murine IVC. By immunofluorescence analysis
of human tissue, we determined that a subset of these aorta-enriched
proteins exhibited a primarily intima-restricted expression. Intimal
expression of at least a subset of these genes, plakoglobin, galectin
7, sciellin, and SPRR3, was also detected in other types of arteries
but not in veins. Furthermore, SPRR3 expression in the intima was
primarily associated with atheromas. The proteins identified are
functionally related in that they are known to also be enriched in
stratified epithelia, where they play an important role in stress-bearing
and barrier properties. Conclusions-- Vascular expression of these
genes has not been reported previously. Our observations suggest
that they may play a significant role in the mechanisms by which
large arteries may adapt to biomechanical stress.},
url = {http://circ.ahajournals.org/cgi/content/abstract/111/18/2382}
}
@ARTICLE{Young2003,
author = {Young, William W., Jr. and Holcomb, Dana R. and Ten Hagen, Kelly
G. and Tabak, Lawrence A.},
title = {Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
isoforms in murine tissues determined by real-time PCR: a new view
of a large family},
journal = {Glycobiology},
year = {2003},
volume = {13},
pages = {549--557},
number = {7},
month = jul,
abstract = {The members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
(ppGaNTase) family transfer GalNAc to serine and threonine sites
and initiate mucin-type O-glycosylation. There are at least 13 functionally
characterized family members in mammals. Explanations for the large
size of this enzyme family have included functional redundancy, differences
among isoforms in substrate specificity, and specific expression
of individual isoforms in particular tissues or during certain developmental
stages. To date no quantitative comparison of the levels of all ppGaNTase
isoforms in any tissue of any species has been reported. We performed
real-time polymerase chain reaction using the Taqman method to determine
the expression of ppGaNTase isoforms in mouse tissues. Several tissues
exhibited a common pattern in which isoforms T1 and T2 were the most
strongly expressed, although the level of expression varied widely
among tissues. In striking contrast to this general pattern, testis,
sublingual gland, and colon exhibited distinctive profiles of isoform
expression. Isoform T13 was expressed most strongly in brain, and
one putative isoform was expressed only in testis. In mammary tissue
the expression of several isoforms changed markedly during pregnancy
and lactation. In summary these real-time PCR data indicate the contribution
of each isoform to the overall ppGaNTase expression within each tissue
and highlight the particular isoforms and tissues that will be the
targets of future studies on the functions of the ppGaNTase family.},
url = {http://glycob.oxfordjournals.org/cgi/content/abstract/13/7/549}
}
@ARTICLE{Younossi2005,
author = {Younossi, Zobair M. and Gorreta, Francesco and Ong, Janus P. and
Schlauch, Karen and Del Giacco, Luca and Elariny, Hazem and Van Meter,
Amy and Younoszai, Abraham and Goodman, Zachary and Baranova, Anna
and Christensen, Alan and Grant, Geraldine and Chandhoke, Vikas},
title = {Hepatic gene expression in patients with obesity-related non-alcoholic
steatohepatitis},
journal = {Liver International},
year = {2005},
volume = {25},
pages = {760--771},
number = {4},
abstract = {Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is
among the most common causes of chronic liver disease. NAFLD includes
a spectrum of clinicopathologic syndromes that includes non-alcoholic
steatohepatitis (NASH) that has potential for progression. The pathogenesis
of NASH is poorly characterized. Aim: This study was designed to
identify differences in hepatic gene expression in patients with
NASH and to relate such differences to their clinical characteristics.
Design: Consecutive patients undergoing bariatric surgery were prospectively
recruited. Extensive clinical data and two liver biopsy specimens
were obtained at the time of enrollment. A single hepatopathologist
reviewed and classified the liver biopsies. Patients with excessive
alcohol use and other causes of liver disease were excluded. A group
of 29 NASH patients, 12 with steatosis alone, seven obese controls
and six non-obese controls were selected for further investigation.
Customized cDNA microarrays containing 5220 relevant genes were designed
specifically for this study. Microarray experiments were run in triplicate
for each sample and a selected group of genes were confirmed using
real-time PCR. Outcome Measure: Differential hepatic gene expressions
in patients with NASH as compared with controls. Results: Thirty-four
genes with significant differential expression were identified in
patients with NASH when compared with non-obese controls. Moreover,
19 of these genes showed no significant expression differences in
obese vs. non-obese controls, suggesting a stronger association of
these genes to NASH. Conclusions: Several differentially expressed
genes in patients with NASH are related to lipid metabolism and extracellular
matrix remodeling. Additionally, genes related to liver regeneration,
apoptosis, and the detoxification process were differentially expressed.
These findings may help clarify the molecular pathogenesis of NASH
and identify potential targets for therapeutic intervention.},
issn = {1478-3231},
keywords = {NASH, gene expression, micro arrays},
publisher = {Munksgaard International Publishers},
url = {http://dx.doi.org/10.1111/j.1478-3231.2005.01117.x}
}
@ARTICLE{Youns2011,
author = {Youns, Mahmoud and Efferth, Thomas and Hoheisel, Jörg D.},
title = {Transcript profiling identifies novel key players mediating the growth
inhibitory effect of NS-398 on human pancreatic cancer cells},
journal = {European Journal of Pharmacology},
year = {2011},
volume = {650},
pages = {170--177},
number = {1},
month = jan,
abstract = {Pancreatic cancer is one of the most aggressive human malignancies
with an increasing incidence worldwide. Despite an increase in the
number of systemic treatments available for pancreatic cancer, the
impact of therapy on the clinical course of the disease has been
modest, underscoring an urgent need for new therapeutic options.
Although selective cyclooxygenase-2 inhibitors have been demonstrated
to have cancer-preventive effects, the mechanism of their effects
is not clearly known. Moreover, there have been no unbiased studies
to identify novel molecular targets of NS-398 regarding pancreatic
cancer. Here we undertook a gene expression profiling study to identify
novel molecular targets modulating the growth inhibitory effects
of NS-398 on pancreatic cancer cell lines. Our mRNA-based gene expression
results showed that the growth inhibitory effect of NS-398 was accompanied
with an activation of G1/S and G2/M cell cycle regulation, P53 signalling,
apoptotic, aryl hydrocarbon receptor and death receptor signalling
pathways. Moreover, we reported, for the first time, that the growth
inhibitory effect of NS-398 is mediated by down-regulation of RRM2,
CTGF, MCM2 and PCNA and up-regulation of NAG-1 in all cell lines.},
issn = {0014-2999},
keywords = {Pancreatic cancer, Microarray, Ingenuity, NS-398},
url = {http://www.sciencedirect.com/science/article/pii/S0014299910010484}
}
@ARTICLE{Youns2009,
author = {Youns, Mahmoud and Efferth, Thomas and Reichling, Jürgen and Fellenberg,
Kurt and Bauer, Andrea and Hoheisel, Jörg D.},
title = {Gene expression profiling identifies novel key players involved in
the cytotoxic effect of Artesunate on pancreatic cancer cells},
journal = {Biochemical Pharmacology},
year = {2009},
volume = {78},
pages = {273--283},
number = {3},
month = aug,
issn = {0006-2952},
keywords = {Artesunate, Pancreatic cancer, Microarray, Topoisomerase, Ingenuity
Pathway Analysis},
url = {http://www.sciencedirect.com/science/article/B6T4P-4W4CWJ9-1/2/7610410cfabc4213eca3fb91ff72cfb8}
}
@ARTICLE{Youssef2007,
author = {Youssef, Lama A. and Schuyler, Mark and Gilmartin, Laura and Pickett,
Gavin and Bard, Julie D. J. and Tarleton, Christy A. and Archibeque,
Tereassa and Qualls, Clifford and Wilson, Bridget S. and Oliver,
Janet M.},
title = {Histamine Release from the Basophils of Control and Asthmatic Subjects
and a Comparison of Gene Expression between "Releaser" and "Nonreleaser"
Basophils},
journal = {J. Immunol.},
year = {2007},
volume = {178},
pages = {4584--4594},
number = {7},
month = apr,
abstract = {Most human blood basophils respond to Fc{epsilon}RI cross-linking
by releasing histamine and other inflammatory mediators. Basophils
that do not degranulate after anti-IgE challenge, known as "nonreleaser"
basophils, characteristically have no or barely detectable levels
of the Syk tyrosine kinase. The true incidence of the nonreleaser
phenotype, its relationship (if any) to allergic asthma, and its
molecular mechanism are not well understood. In this study, we report
statistical analyses of degranulation assays performed in 68 control
and 61 asthmatic subjects that establish higher basal and anti-IgE-stimulated
basophil degranulation among the asthmatics. Remarkably, 28% of the
control group and 13% of the asthmatic group were nonreleasers for
all or part of our 4-year long study and cycling between the releaser
and nonreleaser phenotypes occurred at least once in blood basophils
from 8 (of 8) asthmatic and 16 (of 23) control donors. Microarray
analysis showed that basal gene expression was generally lower in
nonreleaser than releaser basophils. In releaser cells, Fc{epsilon}RI
cross-linking up-regulated >200 genes, including genes encoding receptors
(the Fc{epsilon}RI {alpha} and [beta] subunits, the histamine 4 receptor,
the chemokine (C-C motif) receptor 1), signaling proteins (Lyn),
chemokines (IL-8, RANTES, MIP-1{alpha}, and MIP-1[beta]) and transcription
factors (early growth response-1, early growth response-3, and AP-1).
Fc{epsilon}RI cross-linking induced fewer, and quite distinct, transcriptional
responses in nonreleaser cells. We conclude that "nonreleaser" and
"cycler" basophils represent a distinct and reversible natural phenotype.
Although histamine is more readily released from basophils isolated
from asthmatics than controls, the presence of nonreleaser basophils
does not rule out the diagnosis of asthma.},
url = {http://www.jimmunol.org/cgi/content/abstract/178/7/4584}
}
@ARTICLE{Yovchev2007,
author = {Yovchev, Mladen I. and Grozdanov, Petar N. and Joseph, Brigid and
Gupta, Sanjeev and Dabeva, Mariana D.},
title = {Novel hepatic progenitor cell surface markers in the adult rat liver},
journal = {Hepatology},
year = {2007},
volume = {45},
pages = {139--149},
number = {1},
abstract = {Abstract 10.1002/hep.21448.abs Hepatic progenitor/oval cells appear
in injured livers when hepatocyte proliferation is impaired. These
cells can differentiate into hepatocytes and cholangiocytes and could
be useful for cell and gene therapy applications. In this work, we
studied progenitor/oval cell surface markers in the liver of rats
subjected to 2-acetylaminofluorene treatment followed by partial
hepatectomy (2-AAF/PH) by using rat genome 230 2.0 Array chips and
subsequent RT-PCR, immunofluorescent (IF), immunohistochemical (IHC)
and in situ hybridization (ISH) analyses. We also studied expression
of the identified novel cell surface markers in fetal rat liver progenitor
cells and FAO-1 hepatoma cells. Novel cell surface markers in adult
progenitor cells included tight junction proteins, integrins, cadherins,
cell adhesion molecules, receptors, membrane channels and other transmembrane
proteins. From the panel of 21 cell surface markers, 9 were overexpressed
in fetal progenitor cells, 6 in FAO-1 cells and 6 are unique for
the adult progenitors (CD133, claudin-7, cadherin 22, mucin-1, ros-1,
Gabrp). The specificity of progenitor/oval cell surface markers was
confirmed by ISH and double IF analyses. Moreover, study of progenitor
cells purified with Ep-CAM antibodies from D-galactosamine injured
rat liver, a noncarcinogenic model of progenitor cell activation,
verified that progenitor cells expressed these markers. Conclusion:
We identified novel cell surface markers specific for hepatic progenitor/oval
cells, which offers powerful tool for their identification, isolation
and studies of their physiology and pathophysiology. Our studies
also reveal the mesenchymal/epithelial phenotype of these cells and
the existence of species diversity in the hepatic progenitor cell
identity. (HEPATOLOGY 2007;45:139–149.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.21448}
}
@ARTICLE{Yu2009,
author = {Yu, Aixin and Zhu, Linjian and Altman, Norman H. and Malek, Thomas
R.},
title = {A Low Interleukin-2 Receptor Signaling Threshold Supports the Development
and Homeostasis of T Regulatory Cells},
journal = {Immunity},
year = {2009},
volume = {30},
pages = {204--217},
number = {2},
month = feb,
abstract = {Summary Interleukin-2 receptor (IL-2R) signaling is essential for
T regulatory (Treg) cell development and homeostasis. Here, we show
that expression of IL-2R[beta] chains that lack tyrosine residues
important for the association of the adaptor Shc and the transcription
factor STAT5 in IL-2R[beta]-deficient mice resulted in production
of a normal proportion of natural Treg cells that suppressed severe
autoimmunity related with deficiency in IL-2 or IL-2R. These mutant
IL-2R[beta] chains supported suboptimal and transient STAT5 activation
that upregulate the transcription factor Foxp3 to normal amounts
in natural, but not induced, Treg cells. Nevertheless, gene expression
profiling revealed many targets in peripheral natural Treg cells
that were IL-2 dependent and a substantial overlap between the Treg
cell IL-2-dependent gene program and the Treg cell transcriptional
signature. Collectively, these findings demonstrate that a critical,
and perhaps minor, subset of IL-2-dependent targets is indexed to
a low IL-2R signaling threshold and that a substantial proportion
of the Treg cell gene program is regulated by IL-2.},
issn = {1074-7613},
keywords = {CELLIMMUNO},
url = {http://www.sciencedirect.com/science/article/B6WSP-4VGNH0J-2/2/ecf71d8a4e993caafc49a834c2ec02b3}
}
@ARTICLE{Yu2010b,
author = {Yu, Claro and Boon, Denali and McDonald, Shannon L. and Myers, Timothy
G. and Tomioka, Keiko and Nguyen, Hanh and Engle, Ronald E. and Govindarajan,
Sugantha and Emerson, Suzanne U. and Purcell, Robert H.},
title = {Pathogenesis of Hepatitis E Virus and Hepatitis C Virus in Chimpanzees:
Similarities and Differences},
journal = {J. Virol.},
year = {2010},
volume = {84},
pages = {11264--11278},
number = {21},
month = nov,
abstract = {The chimpanzee is the only animal model for investigating the pathogenesis
of viral hepatitis types A through E in humans. Studies of the host
response, including microarray analyses, have relied on the close
relationship between these two primate species: chimpanzee samples
are commonly tested with human-based reagents. In this study, the
host responses to two dissimilar viruses, hepatitis E virus (HEV)
and hepatitis C virus (HCV), were compared in multiple experimentally
infected chimpanzees. Affymetrix U133 + 2.0 human microarray chips
were used to assess the entire transcriptome in serial liver biopsies
obtained over the course of the infections. Respecting the limitations
of microarray probes designed for human target transcripts to effectively
assay chimpanzee transcripts, we conducted probe-level analysis of
the microarray data in conjunction with a custom mapping of the probe
sequences to the most recent human and chimpanzee genome sequences.
Time points for statistical comparison were chosen based on independently
measured viremia levels. Regardless of the viral infection, the alignment
of differentially expressed genes to the human genome sequence resulted
in a larger number of genes being identified when compared with alignment
to the chimpanzee genome sequence. This probably reflects the lesser
refinement of gene annotation for chimpanzees. In general, the two
viruses demonstrated very distinct temporal changes in host response
genes, although both RNA viruses induced genes that were involved
in many of the same biological systems, including interferon-induced
genes. The host response to HCV infection was more robust in the
magnitude and number of differentially expressed genes compared to
HEV infection.},
url = {http://jvi.asm.org/cgi/content/abstract/84/21/11264}
}
@ARTICLE{Yu2010g,
author = {Yu, Cong and Jiang, Shujun and Lu, Jianyun and Coughlin, Carrie C.
and Wang, Yuan and Swietlicki, Elzbieta A. and Wang, Lihua and Vietor,
Ilja and Huber, Lukas A. and Cikes, Domagoj and Coleman, Trey and
Xie, Yan and Semenkovich, Clay F. and Davidson, Nicholas O. and Levin,
Marc S. and Rubin, Deborah C.},
title = {Deletion of Tis7 Protects Mice from High-Fat Diet-Induced Weight
Gain and Blunts the Intestinal Adaptive Response Postresection},
journal = {J. Nutr.},
year = {2010},
volume = {140},
pages = {1907--1914},
number = {11},
month = nov,
abstract = {After loss of intestinal surface area, the remaining bowel undergoes
a morphometric and functional adaptive response. Enterocytic expression
of the transcriptional coregulator tetradecanoyl phorbol acetate
induced sequence 7 (Tis7) is markedly increased in a murine model
of intestinal adaptation. Mice overexpressing Tis7 in intestine have
greater triglyceride absorption and weight gain when fed a high-fat
diet (42% energy) than their wild-type (WT) littermates fed the same
diet. These and other data suggest that Tis7 has a unique role in
nutrient absorptive and metabolic adaptation. Herein, male Tis7-/-
and WT mice were fed a high-fat diet (42% energy) for 8 wk. Weight
was monitored and metabolic analyses and hepatic and intestinal lipid
concentrations were compared after 8 wk. Intestinal lipid absorption
and metabolism studies and intestinal resection surgeries were performed
in separate groups of Tis7-/- and WT mice. At 8 wk, weight gain was
less and jejunal mucosal and hepatic triglyceride and cholesterol
concentrations were lower in Tis7-/- mice than in the WT controls.
Following corn oil gavage, serum cholesterol, triglyceride, and FFA
concentrations were lower in the Tis7-/- mice than in the WT mice.
Incorporation of oral 3[H] triolein into intestinal mucosal cholesterol
ester and FFA was less in Tis7-/- compared with WT mice. Following
resection, crypt cell proliferation rates and villus heights were
lower in Tis7-/- than in WT mice, indicating a blunted adaptive response.
Our results suggest a novel physiologic function for Tis7 in the
gut as a global regulator of lipid absorption and metabolism and
epithelial cell proliferation.},
url = {http://jn.nutrition.org/cgi/content/abstract/140/11/1907}
}
@ARTICLE{Yu2008,
author = {Yu, Charles Q. and Zhang, Min and Matis, Krisztina I. and Kim, Charles
and Rosenblatt, Mark I.},
title = {Vascular Endothelial Growth Factor Mediates Corneal Nerve Repair},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2008},
volume = {49},
pages = {3870--3878},
number = {9},
month = sep,
abstract = {PURPOSE. To examine the expression of vascular endothelial growth
factor (VEGF) and its receptors in the cornea and the trigeminal
ganglion and to characterize the role of VEGF in mediating corneal
nerve repair. METHODS. Regeneration of the corneal subbasal nerve
plexus after epithelial debridement was measured. The expression
of VEGF and its receptors was examined in the trigeminal ganglia
and in the cornea by RT-PCR, immunohistochemistry, and Western blotting.
VEGF-mediated nerve growth was measured in a trigeminal ganglia explant
assay. Anti-VEGF neutralizing antibody was used to examine the VEGF-dependent
growth of neurons in vitro and regeneration of the corneal nerves
in vivo. RESULTS. After two distinct patterns of nerve regeneration,
the subbasal nerves recovered to 65% of the preinjury density after
28 days. RT-PCR demonstrated gene expression of VEGF and VEGF receptors
in the trigeminal ganglia. Immunohistochemistry showed staining for
VEGF and its receptors in the trigeminal ganglia and for VEGFR1,
VEGFR2, and neuropilin (NRP)-1 in the cornea. Western blot confirmed
these results. In vitro, VEGF promoted the growth of explanted trigeminal
ganglia by 91%. Blockage of VEGF signaling with anti-VEGF antibody
reduced the growth of cultured neurons by 17% and the regeneration
of subbasal neurons by 23%. CONCLUSIONS. In addition to providing
new information on the regeneration of murine corneal nerves, this
study presents evidence that VEGF signaling influences the repair
of corneal nerves by demonstrating that VEGF and VEGF receptors are
present in the trigeminal ganglia and that abrogation of VEGF signaling
reduces nerve growth in vitro and in vivo.},
url = {http://www.iovs.org/cgi/content/abstract/49/9/3870}
}
@ARTICLE{Yu2011,
author = {Yu, Hua and Lu, Changwan and Tan, Ming and Moudgil, Kamal},
title = {The gene expression profile of preclinical autoimmune arthritis and
its modulation by a tolerogenic disease-protective antigenic challenge},
journal = {Arthritis Research \& Therapy},
year = {2011},
volume = {13},
pages = {R143},
number = {5},
abstract = {INTRODUCTION:Autoimmune inflammation is a characteristic feature of
rheumatoid arthritis (RA) and other autoimmune diseases. In the natural
course of human autoimmune diseases, it is rather difficult to pinpoint
the precise timing of the initial event that triggers the cascade
of pathogenic events that later culminate into clinically overt disease.
Therefore, it is a challenge to examine the early preclinical events
in these disorders. Animal models are an invaluable resource in this
regard. Furthermore, considering the complex nature of the pathogenic
immune events in arthritis, microarray analysis offers a versatile
tool to define the dynamic patterns of gene expression during the
disease course.METHODS:In this study, we defined the profiles of
gene expression at different phases of adjuvant arthritis (AA) in
Lewis rats and compared them with those of antigen mycobacterial
heat shock protein 65 (Bhsp65)-tolerized syngeneic rats. Purified
total RNA (100 ng) extracted from the draining lymph node cells was
used to generate biotin-labeled fragment cRNA, which was then hybridized
with an oligonucleotide-based DNA microarray chip. Significance analysis
of microarrays was used to compare gene expression levels between
the two different groups by limiting the false discovery rate to
< 5%. Some of the data were further analyzed using a fold change
[greater than or equal to]2.0 as the cutoff. The gene expression
of select genes was validated by quantitative real-time PCR.RESULTS:Intriguingly,
the most dramatic changes in gene expression in the draining lymphoid
tissue ex vivo were observed at the preclinical (incubation) phase
of the disease. The affected genes represented many of the known
proteins that participate in the cellular immune response. Interestingly,
the preclinical gene expression profile was significantly altered
by a disease-modulating, antigen-based tolerogenic regimen. The changes
mostly included upregulation of several genes, suggesting that immune
tolerance suppressed disease by activating disease-regulating pathways.
We identified a molecular signature comprising at least 12 arthritis-related
genes altered by Bhsp65-induced tolerance.CONCLUSIONS:This is the
first report of microarray analysis in the rat AA model. The results
of this study not only advance our understanding of the early phase
events in autoimmune arthritis but also help in identifying potential
targets for the immunomodulation of RA.},
doi = {10.1186/ar3457},
issn = {1478-6354},
pubmedid = {21914168},
url = {http://arthritis-research.com/content/13/5/R143}
}
@ARTICLE{Yu2011b,
author = {Yu, Haiyuan and Tardivo, Leah and Tam, Stanley and Weiner, Evan and
Gebreab, Fana and Fan, Changyu and Svrzikapa, Nenad and Hirozane-Kishikawa,
Tomoko and Rietman, Edward and Yang, Xinping and Sahalie, Julie and
Salehi-Ashtiani, Kourosh and Hao, Tong and Cusick, Michael E and
Hill, David E and Roth, Frederick P and Braun, Pascal and Vidal,
Marc},
title = {Next-generation sequencing to generate interactome datasets},
journal = {Nat Meth},
year = {2011},
volume = {advance online publication},
pages = {--},
month = apr,
comment = {10.1038/nmeth.1597},
issn = {1548-7105},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nmeth.1597}
}
@ARTICLE{Yu2009a,
author = {Yu, J. and Deshmukh, H. and Gutmann, R. J. and Emnett, R. J. and
Rodriguez, F. J. and Watson, M. A. and Nagarajan, R. and Gutmann,
D. H.},
title = {Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic
astrocytoma},
journal = {Neurology},
year = {2009},
volume = {73},
pages = {1526--1531},
number = {19},
month = nov,
abstract = {Objective: Independent studies have previously demonstrated that both
the HIPK2 and BRAF genes are amplified and rearranged, respectively,
in pilocytic astrocytomas (PAs). The purpose of this study was to
further investigate the frequency of BRAF and HIPK2 alterations in
PAs, the concordance of these events, and their relationship to clinical
phenotype. Methods: We performed extensive characterization by array-based
copy number assessment (aCGH), HIPK2 copy number analysis, and BRAF
rearrangement and mutation analysis in a set of 79 PAs, including
9 tumors from patients with neurofibromatosis type 1 (NF1). Results:
We identified 1 of 3 previously identified BRAF rearrangements in
42/70 sporadic PAs. An additional 2 tumors with no rearrangement
also exhibited BRAF mutation, including a novel 3-base insertion.
As predicted from the genomic organization at this locus, 22/36 tumors
with BRAF rearrangement also exhibited corresponding HIPK2 amplification.
However, 14/36 tumors with BRAF rearrangement had no detectable HIPK2
gene amplification and 6/20 tumors demonstrated HIPK2 amplification
without apparent BRAF rearrangement or mutation. Only 12/70 PAs lacked
detectable BRAF or HIPK2 alterations. Importantly, none of the 9
PA tumors from NF1 patients exhibited BRAF rearrangement or mutation.
Conclusions: BRAF rearrangement represents the most common genetic
alteration in sporadic, but not neurofibromatosis type 1-associated,
pilocytic astrocytomas (PAs). These findings implicate BRAF in the
pathogenesis of these common low-grade astrocytomas in children,
and suggest that PAs arise either from NF1 inactivation or BRAF gain
of function.},
url = {http://www.neurology.org/cgi/content/abstract/73/19/1526}
}
@ARTICLE{Yu2010,
author = {Yu, Jiashing and Du, Kim T. and Fang, Qizhi and Gu, Yiping and Mihardja,
Shirley S. and Sievers, Richard E. and Wu, Joseph C. and Lee, Randall
J.},
title = {The use of human mesenchymal stem cells encapsulated in RGD modified
alginate microspheres in the repair of myocardial infarction in the
rat},
journal = {Biomaterials},
year = {2010},
volume = {31},
pages = {7012--7020},
number = {27},
month = sep,
abstract = {The combination of scaffold material and cell transplantation therapy
has been extensively investigated in cardiac tissue engineering.
However, many polymers are difficult to administer or lack the structural
integrity to restore LV function. Additionally, polymers need to
be biological friendly, favorably influence the microenvironment
and increase stem cell retention and survival. This study determined
whether human mesenchymal stem cells (hMSCs) encapsulated in RGD
modified alginate microspheres are capable of facilitating myocardial
repair. The in vitro study of hMSCs demonstrated that the RGD modified
alginate can improve cell attachment, growth and increase angiogenic
growth factor expression. Alginate microbeads and hMSCs encapsulated
in microbeads successfully maintained LV shape and prevented negative
LV remodeling after an MI. Cell survival was significantly increased
in the encapsulated hMSC group compared with PBS control or cells
alone. Microspheres, hMSCs, and hMSCs in microspheres groups reduced
infarct area and enhanced arteriole formation. In summary, surface
modification and microencapsulation techniques can be combined with
cell transplantation leading to the maintenance of LV geometry, preservation
of LV function, increase of angiogenesis and improvement of cell
survival.},
issn = {0142-9612},
keywords = {Mesenchymal stem cells, Alginate, Myocardial infarction, RGD peptides},
url = {http://www.sciencedirect.com/science/article/B6TWB-50BRJWN-4/2/0af38f16655df56cc47434af87b2e48d}
}
@ARTICLE{Yu2010c,
author = {Yu, Jun and Li, Yan and Li, Mincai and Qu, Zhiling and Ruan, Qiurong},
title = {Oxidized low density lipoprotein-induced transdifferentiation of
bone marrow-derived smooth muscle-like cells into foam-like cells
in vitro},
journal = {International Journal of Experimental Pathology},
year = {2010},
volume = {91},
pages = {24--33},
number = {1},
abstract = {Summary Oxidized-low density lipoprotein (ox-LDL) is believed to contribute
to atherogenesis in part by being taken up into smooth muscle cells
(SMC) via specific scavenger receptors; however, it is not clear
whether ox-LDL receptor(s) are expressed in bone marrow-derived smooth
muscle-like cells (SMLCs) and whether they play a role in the process
of SMLC development. Therefore, we examined the ox-LDL-induced transdifferentiation
of SMLCs that is mediated by lectin-like ox-LDL receptor-1 (LOX-1).
Smooth muscle progenitor cells (SMPCs) from bone marrow mesenchymal
stem cells (BMSCs) were isolated using a tissue-specific promoter
sorting method with a mouse SM22_ promoter (_480Â bp)/green fluorescent
protein recombinant plasmid. The SMPCs were myocardin+CD105+KDR+CD45−CD34−,
but did not express SMC-specific markers α-smooth muscle actin (α-SMA),
SM22, smooth muscle myosin heavy chain (SM-MHC) and smoothelin. After
long-term culture with platelet-derived growth factor-BB (PDGF-BB),
SMPCs expressed α-SMA, SM22 and SM-MHC and differentiated into SMLCs.
When SMLCs were incubated with different concentrations of ox-LDL,
LOX-1 expression on the surface of SMLCs gradually increased with
the increase of the ox-LDL concentration, but myocardin and SMC-specific
marker genes decreased, accordingly. Furthermore, receptor-mediated
endocytosis was enhanced and lipid droplets accumulated in the cytoplasm
of SMLCs. A subpopulation of myocardin+CD105+KDR+CD45−CD34− SMPCs
exist in BMSCs that can differentiate into SMLCs under induction
with PDGF-BB. Moreover, LOX-1 contributes to the ox-LDL-induced transdifferentiation
of bone marrow-derived SMLCs into foam-like cells.},
issn = {1365-2613},
keywords = {atherosclerosis, mesenchymal stem cells, LOX-1, smooth muscle progenitor
cells, transdifferentiation},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2613.2009.00693.x}
}
@ARTICLE{Yu2009b,
author = {Yu, Jun and Rossi, Raffaella and Hale, Christine and Goulding, David
and Dougan, Gordon},
title = {Interaction of Enteric Bacterial Pathogens with Murine Embryonic
Stem Cells},
journal = {Infect. Immun.},
year = {2009},
volume = {77},
pages = {585--597},
number = {2},
month = feb,
abstract = {Embryonic stem (ES) cells are susceptible to genetic manipulation
and retain the potential to differentiate into diverse cell types,
which are factors that make them potentially attractive cells for
studying host-pathogen interactions. Murine ES cells were found to
be susceptible to invasion by Salmonella enterica serovar Typhimurium
and Shigella flexneri and to the formation of attaching and effacing
lesions by enteropathogenic Escherichia coli. S. enterica serovar
Typhimurium and S. flexneri cell entry was dependent on the Salmonella
pathogenicity island 1 and Shigella mxi/spa type III secretion systems,
respectively. Microscopy studies indicated that both S. enterica
serovar Typhimurium and S. flexneri were located in intracellular
niches in ES cells that were similar to the niches occupied in differentiated
cells. ES cells were eventually killed following bacterial invasion,
but no evidence of activation of classical caspase-associated apoptotic
or innate immune pathways was found. To demonstrate the potential
of mutant ES cells, we employed an ES cell line defective in cholesterol
synthesis and found that the mutant cells were less susceptible to
infection by Salmonella and Shigella than the parental ES cells.
Thus, we highlighted the practical use of genetically modified ES
cells for studying microbe-host interactions.},
url = {http://iai.asm.org/cgi/content/abstract/77/2/585}
}
@ARTICLE{Yu2010e,
author = {Yu, Jin and Yin, Peng and Liu, Fenghua and Cheng, Guilin and Guo,
Kaijun and Lu, An and Zhu, Xiaoyu and Luan, Weili and Xu, Jianqin},
title = {Effect of heat stress on the porcine small intestine: A morphological
and gene expression study},
journal = {Comparative Biochemistry and Physiology - Part A: Molecular \& Integrative
Physiology},
year = {2010},
volume = {156},
pages = {119--128},
number = {1},
month = may,
abstract = {With the presence of global warming, the occurrence of extreme heat
is becoming more common, especially during the summer, increasing
pig susceptibility to severe heat stress. The aim of the current
study was to investigate changes in morphology and gene expression
in the pig small intestine in response to heat stress. Forty eight
Chinese experimental mini pigs (Sus scrofa) were subjected to 40 °C
for 5 h each day for 10 successive days. Pigs were euthanized at
1, 3, 6, and 10 days after heat treatment and sections of the small
intestine epithelial tissue were excised for morphological examination
and microarray analyses. After heat treatment, the pig rectal temperature,
the body surface temperature and serum cortisol levels were all significantly
increased. The duodenum and jejunum displayed significant damage,
most severe after 3 days of treatment. Microarray analysis found
93 genes to be up-regulated and 110 genes to be down-regulated in
response to heat stress. Subsequent bioinformatic analysis (including
gene ontology and KEGG pathway analysis) revealed the genes altered
in response to heat stress related to unfolded protein, regulation
of translation initiation, regulation of cell proliferation, cell
migration and antioxidant regulation. Heat stress caused significant
damage to the pig small intestine and altered gene expression in
the pig jejunum. The results of the bioinformatic analysis from the
present study will be beneficial to further investigate the underlying
mechanisms involved in heat stress-induced damage in the pig small
intestine.},
issn = {1095-6433},
keywords = {Heat stress, Morphology, Gene expression, Electron microscope, Microarray,
Small intestine, Pig},
url = {http://www.sciencedirect.com/science/article/B6VNH-4Y70CCB-1/2/fd3e55c18d47f010eb2b307242e54dc7}
}
@ARTICLE{Yu2010a,
author = {Yu, Ji Hoon and Zhu, Bing-Mei and Wickre, Mark and Riedlinger, Gregory
and Chen, Weiping and Hosui, Atsushi and Robinson, Gertraud W. and
Hennighausen, Lothar},
title = {The transcription factors signal transducer and activator of transcription
5A (STAT5A) and STAT5B negatively regulate cell proliferation through
the activation of cyclin-dependent kinase inhibitor 2b (Cdkn2b) and
Cdkn1a expression},
journal = {Hepatology},
year = {2010},
volume = {52},
pages = {1808--1818},
number = {5},
abstract = {Abstract Although the cytokine-inducible transcription factor signal
transducer and activator of transcription 5 (STAT5) promotes proliferation
of a wide range of cell types, there are cell-specific and context-specific
cases in which loss of STAT5 results in enhanced cell proliferation.
Here, we report that loss of STAT5 from mouse embryonic fibroblasts
(MEFs) leads to enhanced proliferation, which was linked to reduced
levels of the cell cycle inhibitors p15INK4B and p21CIP1. We further
demonstrate that growth hormone, through the transcription factor
STAT5, enhances expression of the Cdkn2b (cyclin-dependent kinase
inhibitor 2B) gene and that STAT5A binds to interferon-gamma–activated
sequence sites within the promoter. We recently demonstrated that
ablation of STAT5 from liver results in hepatocellular carcinoma
upon CCl4 treatment. We now establish that STAT5, like in MEFs, activates
expression of the Cdkn2b gene in liver tissue. Loss of STAT5 led
to diminished p15INK4B and increased hepatocyte proliferation. Conclusion:
This study for the first time demonstrates that cytokines, through
STAT5, induce the expression of a key cell cycle inhibitor. These
experiments therefore shed mechanistic light on the context-specific
role of STAT5 as tumor suppressor. (HEPATOLOGY 2010;52:1808-1818)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.23882}
}
@ARTICLE{Yu2010f,
author = {Yu, Lei and Todd, Nevins W. and Xing, Lingxiao and Xie, Ying and
Zhang, Howard and Liu, Zhenqiu and Fang, HongBin and Zhang, Jian
and Katz, Ruth L. and Jiang, Feng},
title = {Early detection of lung adenocarcinoma in sputum by a panel of microRNA
markers},
journal = {Int. J. Cancer},
year = {2010},
volume = {127},
pages = {2870--2878},
number = {12},
abstract = {Abstract Adenocarcinoma is the most common type of lung cancer, the
leading cause of cancer deaths in the world. Early detection is the
key to improve the survival of lung adenocarcinoma patients. We have
previously shown that microRNAs (miRNAs) were stably present in sputum
and could be applied to diagnosis of lung cancer. The aim of our
study was to develop a panel of miRNAs that can be used as highly
sensitive and specific sputum markers for early detection of lung
adenocarcinoma. Our study contained 3 phases: (i) marker discovery
using miRNA profiling on paired normal and tumor lung tissues from
20 patients with lung adenocarcinoma; (ii) marker optimization by
real-time reverse transcription-quantitative polymerase chain reaction
on sputum of a case–control cohort consisting of 36 cancer patients
and 36 health individuals and (iii) validation on an independent
set of 64 lung cancer patients and 58 cancer-free subjects. From
the surgical tissues, 7 miRNAs with significantly altered expression
were identified, of which “4� were overexpressed and “3�
were underexpressed in all 20 tumors. On the sputum samples of the
case–control cohort, 4 (miR-21, miR-486, miR-375 and miR-200b)
of the 7 miRNAs were selected, which in combination produced the
best prediction in distinguishing lung adenocarcinoma patients from
normal subjects with 80.6% sensitivity and 91.7% specificity. Validation
of the marker panel in the independent populations confirmed the
sensitivity and specificity that provided a significant improvement
over any single one alone. The sputum markers demonstrated the potential
of translation to laboratory settings for improving the early detection
of lung adenocarcinoma.},
issn = {1097-0215},
keywords = {microRNA, sputum, lung adenocarcinoma, real-time RT-qPCR, diagnosis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.25289}
}
@ARTICLE{Yu2010d,
author = {Yu, Mei and Bell, Robert H. and Ross, Elizabeth K. and Lo, Blanche
K.K. and Isaac-Renton, Megan and Martinka, Magda and Haegert, Anne
and Shapiro, Jerry and McElwee, Kevin J.},
title = {Lichen planopilaris and pseudopelade of Brocq involve distinct disease
associated gene expression patterns by microarray},
journal = {Journal of Dermatological Science},
year = {2010},
volume = {57},
pages = {27--36},
number = {1},
month = jan,
abstract = {Background Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB)
are two scarring alopecia diagnoses that exhibit similar clinical
features. Some suggest LPP and PPB are not distinct diseases, but
rather different clinical presentations in a spectrum derived from
the same underlying pathogenic mechanism.Objective We explored the
degree of similarity between LPP and PPB gene expression patterns
and the potential for common and unique gene pathway and gene activity
in LPP and PPB using microarrays.Methods Microarray analysis, using
a 21K cDNA set, was performed on pairs of biopsies obtained from
affected and unaffected scalp of untreated patients. Diagnosis was
confirmed by histopathology. Significantly differentially expressed
genes were identified by analysis of microarray results in various
datasets and screened for signaling pathway involvement. Selected
genes were validated by quantitative PCR and immunohistology.Results
The global gene expression profiles in LPP and PPB versus comparative
intra-control scalp tissue were distinguishable by significance analysis
of microarrays (SAM). There was limited commonality in the gene expression
profiles between LPP and PPB. Specific genes, such as MMP11, TNFSF13B,
and APOL2, were identified with significantly differential expression
in association with LPP versus PPB.Conclusions Our findings may have
important implications for understanding the pathogenesis of LPP
and PPB at the molecular level. Results suggest LPP and PPB involve
different mechanisms of disease development and should be regarded
as biologically distinct cicatricial alopecia diagnoses. Genes that
we have identified may be useful as markers of the respective diagnoses
and may be potential therapeutic targets.},
issn = {0923-1811},
keywords = {Lichen planopilaris, Pseudopelade of Brocq, Cicatricial alopecia,
Microarray},
url = {http://www.sciencedirect.com/science/article/B6T87-4XS0D5V-1/2/615db5190030c5ccfcaaf60c24352754}
}
@ARTICLE{Yu2011c,
author = {Yu, Shuyang and Cui, Kairong and Jothi, Raja and Zhao, Dong-Mei and
Jing, Xuefang and Zhao, Keji and Xue, Hai-Hui},
title = {GABP controls a critical transcription regulatory module that is
essential for maintenance and differentiation of hematopoietic stem/progenitor
cells},
journal = {Blood},
year = {2011},
volume = {117},
pages = {2166--2178},
number = {7},
month = feb,
abstract = {Maintaining a steady pool of self-renewing hematopoietic stem cells
(HSCs) is critical for sustained production of multiple blood lineages.
Many transcription factors and molecules involved in chromatin and
epigenetic modifications have been found to be critical for HSC self-renewal
and differentiation; however, their interplay is less understood.
The transcription factor GA binding protein (GABP), consisting of
DNA-binding subunit GABP and transactivating subunit GABP{beta},
is essential for lymphopoiesis as shown in our previous studies.
Here we demonstrate cell-intrinsic, absolute dependence on GABP for
maintenance and differentiation of hematopoietic stem/progenitor
cells. Through genome-wide mapping of GABP binding and transcriptomic
analysis of GABP-deficient HSCs, we identified Zfx and Etv6 transcription
factors and prosurvival Bcl-2 family members including Bcl-2, Bcl-XL,
and Mcl-1 as direct GABP target genes, underlying its pivotal role
in HSC survival. GABP also directly regulates Foxo3 and Pten and
hence sustains HSC quiescence. Furthermore, GABP activates transcription
of DNA methyltransferases and histone acetylases including p300,
contributing to regulation of HSC self-renewal and differentiation.
These systematic analyses revealed a GABP-controlled gene regulatory
module that programs multiple aspects of HSC biology. Our studies
thus constitute a critical first step in decoding how transcription
factors are orchestrated to regulate maintenance and multipotency
of HSCs.},
comment = {10.1182/blood-2010-09-306563},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/117/7/2166}
}
@ARTICLE{Yu2006,
author = {Yu, Tao and Traina, Joseph A. and Pungor Jr., Erno and McCaman, Michael},
title = {Precise and comparative pegylation analysis by microfluidics and
mass spectrometry},
journal = {Analytical Biochemistry},
year = {2006},
volume = {359},
pages = {54--62},
number = {1},
month = dec,
abstract = {Standard SDS-PAGE analysis of a pegylated protein was able to confirm
an increase in its molecular size after reaction with an activated
polyethylene glycol (PEG) but could do little to identify the extent
of pegylation or to support characterization of the consistency of
the modified protein. In this article, we demonstrate the utility
of the capillary electrophoresis technology (using a microfluidic
system) in analyzing the pegylation pattern of a recombinant protein
over a range of 1-12 PEGs per polypeptide. Confirmatory data from
mass spectrometry analysis of pegylated adducts are also presented.
These allowed independent confirmation of the extent of pegylation.
This electrophoretic analysis gives a robust, reproducible, and direct
characterization of PEG adducts. We found that traditional estimation
of PEG adducts by an indirect colorimetric (trinitrobenzene sulfonic
acid) reaction, which detects loss of free amino groups, was quite
erroneous for the recombinant protein in our study as well as several
commercially available pegylated proteins. These results support
the use of this capillary electrophoresis device for precise characterization
of pegylated proteins.},
issn = {0003-2697},
keywords = {Pegylation, Microfluidics, Protein characterization, Capillary electrophoresis},
url = {http://www.sciencedirect.com/science/article/B6W9V-4KTMSMT-1/2/b87fc8081008b9116b457ebaedf5139a}
}
@ARTICLE{Yu2008a,
author = {Yu, Wenli and Kamara, Harold and Svoboda, Kathy K. H.},
title = {The role of twist during palate development},
journal = {Dev. Dyn.},
year = {2008},
volume = {237},
pages = {2716--2725},
number = {10},
abstract = {Abstract In palatogenesis, the MEE (Medial Edge Epithelium) cells
disappear when palates fuse. We hypothesize that the MEE cells undergo
EMT (Epithelial-Mesenchymal Transition) to achieve mesenchyme confluence.
Twist has an important role in EMT for tumor metastasis. The purpose
of this study was to analyze Twist function during palatal fusion.
Twist protein was expressed in palatal shelves and MEE both in vivo
and in vitro just prior to fusion. Twist mRNA increased in chicken
palates 3 and 6 hr after TGFβ3 treatment. Palatal fusion was decreased
when cultured palatal shelves were treated with 200 nM Twist siRNA
and the subcellular localization of β-catenin was altered. Twist
mRNA decreased in palatal shelves treated with TGFβ3 neutralizing
antibody or LY294002, a specific phosphatidylinositol-3 kinase (PI-3K)
inhibitor. In summary, Twist is downstream of TGFβ3 and PI-3K pathways
during palatal fusion. However, decreasing Twist with siRNA did not
completely block palate fusion, indicating that the function of Twist
may be duplicated by other transcription factors. Developmental Dynamics
237:2716–2725, 2008. © 2008 Wiley-Liss, Inc.},
issn = {1097-0177},
keywords = {palate, TGFβ3, Twist},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.21627}
}
@ARTICLE{Yu2009c,
author = {Yu, Xiaozhong and Hong, SungWoo and Moreira, Estefania G. and Faustman,
Elaine M.},
title = {Improving in vitro Sertoli cell/gonocyte co-culture model for assessing
male reproductive toxicity: Lessons learned from comparisons of cytotoxicity
versus genomic responses to phthalates},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {239},
pages = {325--336},
number = {3},
month = sep,
abstract = {Gonocytes exist in the neonatal testis and represent a transient population
of male germ-line stem cells. It has been shown that stem cell self-renewal
and progeny production is probably controlled by the neighboring
differentiated cells and extracellular matrix (ECM) in vivo known
as niches. Recently, we developed an in vitro three-dimensional (3D)
Sertoli cell/gonocyte co-culture (SGC) model with ECM overlay, which
creates an in vivo-like niche and supports germ-line stem cell functioning
within a 3D environment. In this study, we applied morphological
and cytotoxicity evaluations, as well as microarray-based gene expression
to examine the effects of different phthalate esters (PE) on this
model. Known in vivo male developmentally toxic PEs (DTPE) and developmentally
non-toxic PEs (DNTPE) were evaluated. We observed that DTPE induced
significantly greater dose-dependent morphological changes, a decrease
in cell viability and an increase in cytotoxicity compared to those
treated with DNTPE. Moreover, the gene expression was more greatly
altered by DTPE than by DNTPE and non-supervised cluster analysis
allowed the discrimination of DTPE from the DNTPE. Our systems-based
GO-Quant analysis showed significant alterations in the gene pathways
involved in cell cycle, phosphate transport and apoptosis regulation
with DTPE but not with DNTPE treatment. Disruptions of steroidogenesis
related-gene expression such as Star, Cyp19a1, Hsd17b8, and Nr4a3
were observed in the DTPE group, but not in the DNTPE group. In summary,
our observation on cell viability, cytotoxicity, and microarray-based
gene expression analysis induced by PEs demonstrate that our in vitro
3D-SGC system mimicked in vivo responses for PEs and suggests that
the 3D-SGC system might be useful in identifying developmental reproductive
toxicants.},
issn = {0041-008X},
keywords = {Sertoli cell/gonocyte co-culture, Male reproductive toxicity, Microarray,
Phthalate esters},
url = {http://www.sciencedirect.com/science/article/B6WXH-4WM74Y3-1/2/97cbd677f4ea6a6106501ce47719abbc}
}
@ARTICLE{Yu2008b,
author = {Yu, Xiaozhong and Robinson, Joshua F. and Gribble, Elizabeth and
Hong, Sung Woo and Sidhu, Jaspreet S. and Faustman, Elaine M.},
title = {Gene expression profiling analysis reveals arsenic-induced cell cycle
arrest and apoptosis in p53-proficient and p53-deficient cells through
differential gene pathways},
journal = {Toxicology and Applied Pharmacology},
year = {2008},
volume = {233},
pages = {389--403},
number = {3},
month = dec,
abstract = {Arsenic (As) is a well-known environmental toxicant and carcinogen
as well as an effective chemotherapeutic agent. The underlying mechanism
of this dual capability, however, is not fully understood. Tumor
suppressor gene p53, a pivotal cell cycle checkpoint signaling protein,
has been hypothesized to play a possible role in mediating As-induced
toxicity and therapeutic efficiency. In this study, we found that
arsenite (As3+) induced apoptosis and cell cycle arrest in a dose-dependent
manner in both p53+/+ and p53-/- mouse embryonic fibroblasts (MEFs).
There was, however, a distinction between genotypes in the apoptotic
response, with a more prominent induction of caspase-3 in the p53-/-
cells than in the p53+/+ cells. To examine this difference further,
a systems-based genomic analysis was conducted comparing the critical
molecular mechanisms between the p53 genotypes in response to As3+.
A significant alteration in the Nrf2-mediated oxidative stress response
pathway was found in both genotypes. In p53+/+ MEFs, As3+ induced
p53-dependent gene expression alterations in DNA damage and cell
cycle regulation genes. However, in the p53-/- MEFs, As3+ induced
a significant up-regulation of pro-apoptotic genes (Noxa) and down-regulation
of genes in immune modulation. Our findings demonstrate that As-induced
cell death occurs through a p53-independent pathway in p53 deficient
cells while apoptosis induction occurs through p53-dependent pathway
in normal tissue. This difference in the mechanism of apoptotic responses
between the genotypes provides important information regarding the
apparent dichotomy of arsenic's dual mechanisms, and potentially
leads to further advancement of its utility as a chemotherapeutic
agent.},
issn = {0041-008X},
keywords = {Arsenite/Arsenic, Gene expression profiling, p53, Cell cycle regulation,
Apoptosis and oxidative stress},
url = {http://www.sciencedirect.com/science/article/B6WXH-4TJ6F8Y-2/2/ac415c80c31dd4ff5595609b015e7ffd}
}
@ARTICLE{Yu2010h,
author = {Yu, Xiaozhong and Robinson, Joshua F. and Sidhu, Jaspreet S. and
Hong, Sungwoo and Faustman, Elaine M.},
title = {A System-Based Comparison of Gene Expression Reveals Alterations
in Oxidative Stress, Disruption of Ubiquitin-Proteasome System and
Altered Cell Cycle Regulation after Exposure to Cadmium and Methylmercury
in Mouse Embryonic Fibroblast},
journal = {Toxicol. Sci.},
year = {2010},
volume = {114},
pages = {356--377},
number = {2},
month = apr,
abstract = {Environmental and occupational exposures to heavy metals such as methylmercury
(MeHg) and cadmium (Cd) pose significant health risks to humans,
including neurotoxicity. The underlying mechanisms of their toxicity,
however, remain to be fully characterized. Our previous studies with
Cd and MeHg have demonstrated that the perturbation of the ubiquitin-proteasome
system (UPS) was associated with metal-induced cytotoxicity and apoptosis.
We conducted a microarray-based gene expression analysis to compare
metal-altered gene expression patterns with a classical proteasome
inhibitor, MG132 (0.5{micro}M), to determine whether the disruption
of the UPS is a critical mechanism of metal-induced toxicity. We
treated mouse embryonic fibroblast cells at doses of MeHg (2.5{micro}M)
and Cd (5.0{micro}M) for 24 h. The doses selected were based on the
neutral red-based cell viability assay where initial statistically
significant decreases in variability were detected. Following normalization
of the array data, we employed multilevel analysis tools to explore
the data, including group comparisons, cluster analysis, gene annotations
analysis (gene ontology analysis), and pathway analysis using GenMAPP
and Ingenuity Pathway Analysis (IPA). Using these integrated approaches,
we identified significant gene expression changes across treatments
within the UPS (Uchl1 and Ube2c), antioxidant and phase II enzymes
(Gsta2, Gsta4, and Noq1), and genes involved in cell cycle regulation
pathways (ccnb1, cdc2a, and cdc25c). Furthermore, pathway analysis
revealed significant alterations in genes implicated in Parkinson's
disease pathogenesis following metal exposure. This study suggests
that these pathways play a critical role in the development of adverse
effects associated with metal exposures.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/114/2/356}
}
@ARTICLE{Yu2005,
author = {Yu, Xiaorui and Tang, Yuhong and Li, Feng and Frank, Mark Barton
and Huang, Hu and Dozmorov, Igor and Zhu, Yanping and Centola, Michael
and Cao, Wei},
title = {Protection against hydrogen peroxide-induced cell death in cultured
human retinal pigment epithelial cells by 17[beta]-estradiol: A differential
gene expression profile},
journal = {Mechanisms of Ageing and Development},
year = {2005},
volume = {126},
pages = {1135--1145},
number = {11},
month = nov,
abstract = {It has been demonstrated that estrogen receptors are present in the
retinal pigment epithelium (RPE)--choroids complex regardless of
sex. This suggests that estrogen could play a functional role in
the outer retina, especially the RPE. To gain further insights on
the molecular mechanisms differentially activated by 17[beta]-estradiol
([beta]E2) in RPE cells, we investigated gene expression changes
in response to [beta]E2 in cultured RPE cells using cDNA microarray
technology. A total of 47 genes among 21,329 human genes are significantly
altered in response to [beta]E2 treatment in RPE cells. Among these
47 altered genes, 34 are up-regulated and 13 are down-regulated by
[beta]E2. The products of 34 genes have a known or suspected function.
These functions belong to various categories, including caspases;
extracellular matrix proteins; metabolism pathway components; GTP/GDP
exchangers and G-protein GTPase activity modulators; transcription
activators and repressors. Six genes which may contribute to the
unique functions of the RPE cells have been validated by both quantitative
real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR.
In addition, we also demonstrated that [beta]E2 quenches H2O2-induced
up-regulation of apoptosis-related protein, and protects RPE cell
degeneration. These results indicate that estrogen regulates functions
of RPE cells and is involved in the maintaining and survival of RPE
cells during oxidative stress, and its deficiency during menopause
period may be a factor contributing to the development of age-related
macular degeneration in elderly women.},
issn = {0047-6374},
keywords = {Estrogen, Retina, Gene},
url = {http://www.sciencedirect.com/science/article/B6T31-4GNCXRT-1/2/bd1e0cad6d8d1ed1b9a39ee49889a54d}
}
@ARTICLE{Yu2011a,
author = {Yu, Ying and Luo, Juan and Mitra, Apratim and Chang, Shuang and Tian,
Fei and Zhang, Huanmin and Yuan, Ping and Zhou, Huijun and Song,
Jiuzhou},
title = {Temporal Transcriptome Changes Induced by MDV in Marek's Disease-Resistant
and -Susceptible Inbred Chickens},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {501},
number = {1},
abstract = {BACKGROUND:Mareks disease (MD) is a lymphoproliferative disease in
chickens caused by Marek's disease virus (MDV) and characterized
by T cell lymphoma and infiltration of lymphoid cells into various
organs such as liver, spleen, peripheral nerves and muscle. Resistance
to MD and disease risk have long been thought to be influenced both
by genetic and environmental factors, the combination of which contributes
to the observed outcome in an individual. We hypothesize that after
MDV infection, genes related to MD-resistance or -susceptibility
may exhibit different trends in chicken lines having varying resistance
to MD.RESULTS:In order to study the mechanisms of resistance and
susceptibility to MD, we performed genome-wide temporal expression
analysis in MD-resistant line 63, susceptible line 72 and recombinant
congenic strain M (RCS-M) chickens, which have a phenotype intermediate
between lines 63 and 72 after MDV infection. Three time points of
the MDV life cycle in chicken were selected for study: 5 days post
infection (dpi), 10dpi and 21dpi, representing the early cytolytic,
latent and late cytolytic stages, respectively. We observed similar
gene expression profiles at the three time points in line 63 and
RCS-M chickens that are different from line 72. Pathway analysis
using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly
influence the chickens irrespective of whether they are resistant
or susceptible to MD. However, some pathways like cardiac arrhythmia
and cardiovascular disease were found to be affected only in line
72; while some networks related to cell-mediated immune response
and antigen presentation were enriched only in line 63 and RCS-M.
We identified 49, 78 and 36 candidate genes associated with MD resistance,
at the three time points respectively, by considering genes having
the same trend of expression change after MDV infection in lines
63 and RCS-M. On the other hand, by considering genes with the same
trend of expression change after MDV infection in lines 72 and RCS-M,
we identified 54, 78 and 43 genes that may be associated with MD-susceptibility.CONCLUSIONS:By
testing temporal transcriptome changes using three representative
chicken lines with different resistance to MD, we identified 163
candidate genes for MD-resistance and 175 candidate genes for MD-susceptibility
over the three time points. Genes included in our resistance or susceptibility
genes lists that are also involved in more than 5 biofunctions, such
as CD8alpha, IL8, USP18, and CTLA4, are considered to be important
genes involved in MD-resistance or -susceptibility. We were also
able to identify several biofunctions related with immune response
that we believe play an important role in MD-resistance.},
doi = {10.1186/1471-2164-12-501},
issn = {1471-2164},
pubmedid = {21992110},
url = {http://www.biomedcentral.com/1471-2164/12/501}
}
@ARTICLE{Yu2010i,
author = {Yu, Yao and Ping, Jie and Chen, Hui and Jiao, Longxian and Zheng,
Siyuan and Han, Ze-Guang and Hao, Pei and Huang, Jian},
title = {A comparative analysis of liver transcriptome suggests divergent
liver function among human, mouse and rat},
journal = {Genomics},
year = {2010},
volume = {96},
pages = {281--289},
number = {5},
month = nov,
abstract = {The human liver plays a vital role in meeting the body's metabolic
needs and maintaining homeostasis. To address the molecular mechanisms
of liver function, we integrated multiple gene expression datasets
from microarray, MPSS, SAGE and EST platforms to generate a transcriptome
atlas of the normal human liver. Our results show that 17396 genes
are expressed in the human liver. 238 genes were identified as liver
enrichment genes, involved in the functions of immune response and
metabolic processes, from the MPSS and EST datasets. A comparative
analysis of liver transcriptomes was performed in humans, mice and
rats with microarray datasets shows that the expression profile of
homologous genes remains significantly different between mouse/rat
and human, suggesting a functional variance and regulation bias of
genes expressed in the livers. The integrated liver transcriptome
data should provide a valuable resource for the in-depth understanding
of human liver biology and liver disease.},
issn = {0888-7543},
keywords = {Transcriptome, Human liver, MPSS, Microarray, SAGE, EST},
url = {http://www.sciencedirect.com/science/article/B6WG1-50W1TD4-1/2/0aa7050ba463abaf8946116b367f6900}
}
@ARTICLE{Yu2011d,
author = {Yu, Zhiqian and Ono, Chiaki and Kim, Helen B and Komatsu, Hiroshi
and Tanabe, Yoichiro and Sakae, Nobutaka and Nakayama, Keiichi I
and Matsuoka, Hiroo and Sora, Ichiro and Bunney, William E and Tomita,
Hiroaki},
title = {Four mood stabilizers commonly induce FEZ1 expression in human astrocytes},
journal = {Bipolar Disorders},
year = {2011},
volume = {13},
pages = {486--499},
number = {5-6},
abstract = {Yu Z, Ono C, Kim HB, Komatsu H, Tanabe Y, Sakae N, Nakayama KI, Matsuoka
H, Sora I, Bunney WE, Tomita H. Four mood stabilizers commonly induce
FEZ1 expression in human astrocytes. Bipolar Disord 2011: 13: 486–499.
© 2011 The Authors. Journal compilation © 2011 John Wiley & Sons
A/S.Objectives:  Mood stabilizers influence the morphology, chemotaxis,
and survival of neurons, which are considered to be related to the
mood-stabilizing effects of these drugs. Although previous studies
suggest glial abnormalities in patients with bipolar disorder and
an effect of mood stabilizers on certain genes in astrocytes, less
is known about the effects of mood stabilizers in astrocytes than
in neurons. The present study identifies a common underlying response
to mood stabilizers in astrocytes.Methods:  Human astrocyte-derived
cells (U-87 MG) were treated with the four most commonly used mood
stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine)
and subjected to microarray gene expression analyses. The most prominently
regulated genes were validated by qRT-PCR and western blot analysis.
The intercellular localization of one of these regulated genes, fasciculation
and elongation protein zeta 1 (FEZ1), was evaluated by immunofluorescence
staining.Results:  The microarray data indicated that FEZ1 was
the only gene commonly induced by the four mood stabilizers in human
astrocyte-derived cells. An independent experiment confirmed astrocytic
FEZ1 induction at both the transcript and protein levels following
mood stabilizer treatments. FEZ1 localized to the cytoplasm of transformed
and primary astrocytes from the human adult brain.Conclusions: 
Our data suggest that FEZ1 may play important roles in human astrocytes,
and that mood stabilizers might exert their cytoprotective and mood-stabilizing
effects by inducing FEZ1 expression in astrocytes.},
doi = {10.1111/j.1399-5618.2011.00946.x},
issn = {1399-5618},
keywords = {astrocyte, bipolar disorder, carbamazepine, FEZ1, lamotrigine, lithium,
mood stabilizer, valproic acid},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-5618.2011.00946.x}
}
@ARTICLE{Yuan2009,
author = {Yuan, A. and Farber, E. L. and Rapoport, A. and Yamashita, C. and
Akhmedov, N. B. and Farber, D. B.},
title = {Embyonic Stem Cell Microvesicles (ESMVs): Signaling in the Niche
and Therapeutic Uses},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2009},
volume = {50},
pages = {1730--},
number = {5},
month = apr,
abstract = {PurposeTo characterize the RNA and protein content of ESMVs and determine
whether they can be engineered to transfer exogenously expressed
proteins and RNA from cell to cell. MethodsES cells (ESCs) expressing
GFP were grown without feeders in serum free media. ESMVs were collected
by differential ultracentrifugation, their RNA profiles obtained
on an Agilent 2100 bioanalyzer and their total protein resolved by
SDS-PAGE. Individual mRNA levels were determined by qRT-PCR and mRNA
integrity was established by comparing the 5'/3' amplicon ratios
of transcripts in ESMVs to those in ESCs. Transfer of GFP to other
ESCs was detected by confocal microscopy after incubation of ESMVs
expressing GFP with ESCs without GFP. Transfer of ESC-specific miRNAs
to mouse embryonic fibroblasts (MEFs) was detected by qRT-PCR after
incubation of MEFs with ESMVs. ResultsESMVs' density, obtained by
equilibrium density ultracentrifugation, is consistent with vesicles
containing mostly lipid and protein. In addition to endogenous mRNA
and proteins expressed in ESCs, we identified in ESMVs mRNA and protein
expressed from a GFP transgene. The GFP mRNA levels were comparable
to those of endogenous transcripts found in ESMVs. The 5'/3' amplicon
ratios for mRNAs isolated from ESMVs and ESCs were not significantly
different, indicating that transcripts found inside ESMVs are protected
from degradation. We also found miRNAs in ESMVs with different relative
abundance to that in ESCs. Using confocal microscopy, we demonstrated
the fusion and transfer of GFP by ESMVs to ESCs as early as 3 h after
incubation. We also showed by qRT-PCR the transfer of miRNAs by ESMVs
to growth-arrested MEFs. ConclusionsESMVs contain exogenously expressed
GFP mRNA and protein in addition to endogenous proteins, mRNA, and
miRNAs. Interestingly, miRNAs and GFP can be transferred to MEFs
and ESCs by ESMVs. ESMVs may be important for intercellular signaling
in stem cell niches and useful as therapeutic tools for transferring
mRNA, protein, and miRNA to the eye without the use of viral vectors.
Furthermore, ESMVs may be a basic method of intercellular communication
within local tissue environments of the eye.},
url = {http://abstracts.iovs.org/cgi/content/abstract/50/5/1730}
}
@ARTICLE{Yuan2007,
author = {Yuan, A. and Rapoport, A. and Kar, S. and Tejada, D. and Yamashita,
C. K. and Akhmedov, N. B. and Farber, D. B.},
title = {Characterization of Embryonic Stem Cell Microvesicles},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2007},
volume = {48},
pages = {1672--},
number = {5},
month = may,
abstract = {PurposeMicrovesicles are membrane-derived vesicles released into the
extracellular space by activated or apoptotic eukaryotic cells. It
has been postulated that microvesicles may serve a role in intercellular
communication. We characterized the RNA and protein content of ESMVs
derived from a mouse ES cell line expressing green fluorescent protein
to determine if exogenously expressed RNA and protein may be delivered
by ESMVs. MethodsES cells were grown without feeders in serum free
media. ESMVs were collected and pelleted by differential ultracentrifugation
or equilibrium density ultracentrifugation. ESMV RNA profiles were
obtained on an Agilent 2100 bioanalyzer and also by 15% denaturing
PAGE for small RNAs. RT-PCR was performed to detect specific transcripts.
MicroRNA microarrays were performed with Ambion Bioarrays. ResultsESMVs
from GFP-expressing ES cells contain exogenously expressed GFP and
RNA. We were able to visualize GFP directly in the vesicles by fluorescence
microscopy. SDS-PAGE analysis of the protein content in ESMVs revealed
several discreet bands representing the most abundant proteins. We
are currently identifying these major protein bands by mass spectroscopy.
In addition to protein, ESMVs amazingly contain a copious supply
of RNA. The total RNA yield from ESMV is 21.0{+/-}2.1 ng/cm2 of ES
cells grown to 70% confluence collected over a 24 hour period. Interestingly,
we were able to detect exogenously expressed GFP mRNA in the ESMVs
in addition to endogenous transcripts such as the transcription factor,
Oct4. Because ESMVs contained such an abundant supply of RNA, we
hypothesized that they might be able to regulate gene expression
in neighboring cells by transferring microRNAs. Thus we looked for
a ubiquitously expressed microRNA, miR-16, by RT-PCR and confirmed
its presence in ES cells and ESMVs. To profile the microRNAs in ESMVs,
we performed microRNA array analysis. Our preliminary results suggest
that certain microRNAs are preferentially packaged into ESMVs. Finally,
using equilibrium density ultracentrifugation, we determined that
the density of ESMVs is 1.18 g/cm3 to 1.29 g/cm3, consistent with
vesicles containing mostly lipid and protein. ConclusionsOur isolated
ESMVs contain exogenously expressed GFP and RNA in addition to endogenous
proteins and RNA. ESMVs may function as physiological liposomes and
may be used to deliver proteins and RNA to cells in vivo. We discovered
microRNAs in ESMVs and thus, one important role of ESMVs during development
might be in intercellular gene expression regulation via the action
of microRNAs.},
url = {http://abstracts.iovs.org/cgi/content/abstract/48/5/1672}
}
@ARTICLE{Yuan2012a,
author = {Yuan, Chaoshen and Lin, Jean Z.H. and Sieglaff, Douglas H. and Ayers,
Steven D. and DeNoto-Reynolds, Frances and Baxter, John D. and Webb,
Paul},
title = {Identical Gene Regulation Patterns of T3 and Selective Thyroid Hormone
Receptor Modulator GC-1},
journal = {Endocrinology},
year = {2012},
volume = {153},
pages = {501-511},
number = {1},
abstract = {Synthetic selective thyroid hormone (TH) receptor (TR) modulators
(STRM) exhibit beneficial effects on dyslipidemias in animals and
humans and reduce obesity, fatty liver, and insulin resistance in
preclinical animal models. STRM differ from native TH in preferential
binding to the TR{beta} subtype vs. TR, increased uptake into liver,
and reduced uptake into other tissues. However, selective modulators
of other nuclear receptors exhibit important gene-selective actions,
which are attributed to differential effects on receptor conformation
and dynamics and can have profound influences in animals and humans.
Although there are suggestions that STRM may exhibit such gene-specific
actions, the extent to which they are actually observed in vivo has
not been explored. Here, we show that saturating concentrations of
the main active form of TH, T3, and the prototype STRM GC-1 induce
identical gene sets in livers of euthyroid and hypothyroid mice and
a human cultured hepatoma cell line that only expresses TR{beta},
HepG2. We find one case in which GC-1 exhibits a modest gene-specific
reduction in potency vs. T3, at angiopoietin-like factor 4 in HepG2.
Investigation of the latter effect confirms that GC-1 acts through
TR{beta} to directly induce this gene but this gene-selective activity
is not related to unusual T3-response element sequence, unlike previously
documented promoter-selective STRM actions. Our data suggest that
T3 and GC-1 exhibit almost identical gene regulation properties and
that gene-selective actions of GC-1 and similar STRM will be subtle
and rare.},
doi = {10.1210/en.2011-1325},
eprint = {http://endo.endojournals.org/cgi/reprint/153/1/501.pdf},
url = {http://endo.endojournals.org/cgi/content/abstract/153/1/501}
}
@ARTICLE{Yuan2009a,
author = {Yuan, Hua and Long, Hua and Liu, Jing and Qu, Lili and Chen, Jingzao
and Mou, Xiang},
title = {Effects of infrasound on hippocampus-dependent learning and memory
in rats and some underlying mechanisms},
journal = {Environmental Toxicology and Pharmacology},
year = {2009},
volume = {28},
pages = {243--247},
number = {2},
month = sep,
abstract = {To investigate the effect of infrasound on the hippocampus-dependent
spatial learning and memory as well as its underlying mechanisms,
we measured the changes of cognitive abilities, brain-derived neurotrophic
factor (BDNF)-tyrosine kinase receptor B (TrkB) signal transduction
pathway and neurogenesis in the hippocampus of rats. The results
showed that rats exposed to infrasound of 16 Hz at 130 dB for 14
days exhibited longer escape latency from day 2 and shortened time
staying in the quadrant P in Morris water maze (MWM). It was found
that mRNA and protein expression levels of hippocampal BDNF and TrkB
were significantly decreased in real-time PCR and Western blot, and
the number of BrdU-labeled cells in hippocampus was also reduced
when compared to control. These results provided novel evidences
that the infrasound of a certain exposure parameter can impair hippocampus-dependent
learning and memory, in which the downregulation of the neuronal
plasticity-related BDNF-TrkB signal pathway and less neurogenesis
in hippocampus might be involved.},
issn = {1382-6689},
keywords = {Infrasound, Learning and memory, Hippocampus, BDNF, TrkB, Neurogenesis},
url = {http://www.sciencedirect.com/science/article/B6T6D-4W4TY0F-2/2/3024b6d85d43ea104656dd9e474ca090}
}
@ARTICLE{Yuan2010a,
author = {Yuan, Joan and Crittenden, Rowena B. and Bender, Timothy P.},
title = {c-Myb Promotes the Survival of CD4+CD8+ Double-Positive Thymocytes
through Upregulation of Bcl-xL},
journal = {J. Immunol.},
year = {2010},
volume = {184},
pages = {2793--2804},
number = {6},
month = mar,
abstract = {Mechanisms that regulate the lifespan of CD4+CD8+ double-positive
(DP) thymocytes help shape the peripheral T cell repertoire. However,
the molecular mechanisms controlling DP thymocyte survival remain
poorly understood. The Myb proto-oncogene encodes a transcription
factor required during multiple stages of T cell development. We
demonstrate that Myb mRNA expression is upregulated as thymocytes
differentiate from the double-negative into the metabolically quiescent,
small, preselection DP stage during T cell development. Using a conditional
deletion mouse model, we demonstrate that Myb-deficient DP thymocytes
undergo premature apoptosis, resulting in a limited Tcr{alpha} repertoire
biased toward 5' J{alpha} segment usage. Premature apoptosis occurs
specifically in the small preselection DP compartment in an {alpha}{beta}TCR-independent
manner and is a consequence of decreased Bcl-xL expression. Forced
Bcl-xL expression is able to rescue survival, and reintroduction
of c-Myb restores both Bcl-xL expression and the small preselection
DP compartment. We further demonstrate that c-Myb promotes transcription
at the Bcl2l1 locus via a genetic pathway that is independent of
the expression of T cell-specific factor-1 or ROR{gamma}t, two transcription
factors that induce Bcl-xL expression in T cell development. Thus,
Bcl-xL is a novel mediator of c-Myb activity during normal T cell
development.},
url = {http://www.jimmunol.org/cgi/content/abstract/184/6/2793}
}
@ARTICLE{Yuan2011,
author = {Yuan, J and Takeuchi, M and Negishi, M and Oguro, H and Ichikawa,
H and Iwama, A},
title = {Bmi1 is essential for leukemic reprogramming of myeloid progenitor
cells},
journal = {Leukemia},
year = {2011},
pages = {--},
month = apr,
issn = {1476-5551},
publisher = {Macmillan Publishers Limited},
url = {http://dx.doi.org/10.1038/leu.2011.85}
}
@ARTICLE{Yuan2009b,
author = {Yuan, JF and Zhang, SJ and Jafer, O and Furlong, RA and Chausiaux,
OE and Sargent, CA and Zhang, GH and Affara, NA},
title = {Global transcriptional response of pig brain and lung to natural
infection by Pseudorabies virus},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {246},
number = {1},
abstract = {BACKGROUND:Pseudorabies virus (PRV) is an alphaherpesviruses whose
native host is pig. PRV infection mainly causes signs of central
nervous system disorder in young pigs, and respiratory system diseases
in the adult.RESULTS:In this report, we have analyzed native host
(piglets) gene expression changes in response to acute pseudorabies
virus infection of the brain and lung using a printed human oligonucleotide
gene set from Illumina. A total of 210 and 1130 out of 23,000 transcript
probes displayed differential expression respectively in the brain
and lung in piglets after PRV infection (p-value < 0.01), with most
genes displaying up-regulation. Biological process and pathways analysis
showed that most of the up-regulated genes are involved in cell differentiation,
neurodegenerative disorders, the nervous system and immune responses
in the infected brain whereas apoptosis, cell cycle control, and
the mTOR signaling pathway genes were prevalent in the infected lung.
Additionally, a number of differentially expressed genes were found
to map in or close to quantitative trait loci for resistance/susceptibility
to pseudorabies virus in piglets.CONCLUSION:This is the first comprehensive
analysis of the global transcriptional response of the native host
to acute alphaherpesvirus infection. The differentially regulated
genes reported here are likely to be of interest for the further
study and understanding of host viral gene interactions.},
doi = {10.1186/1471-2180-9-246},
issn = {1471-2180},
pubmedid = {19948073},
url = {http://www.biomedcentral.com/1471-2180/9/246}
}
@ARTICLE{Yuan2007a,
author = {Yuan, Li and Cao, Ying and Knöchel, Walter},
title = {Endoplasmic reticulum stress induced by tunicamycin disables germ
layer formation in Xenopus laevis embryos},
journal = {Dev. Dyn.},
year = {2007},
volume = {236},
pages = {2844--2851},
number = {10},
abstract = {Abstract 10.1002/dvdy.21299.abs Maintenance of endoplasmic reticulum
(ER) homeostasis is essential for correct protein targeting and secretion.
ER stress caused by accumulation of unfolded or misfolded proteins
leads to disruption of cellular functions. We have investigated the
effect of ER stress on Xenopus embryogenesis. ER stress induced by
tunicamycin (TM) treatment of embryos resulted in defects affecting
germ layer formation. We observed up-regulation of ER stress response
genes, enhanced cytoplasmic splicing of xXBP1 RNA, and increased
rate of apoptosis. In animal cap assays, TM treatment inhibited mesoderm
formation induced by overexpression of activin/nodal RNA but did
not affect mesoderm formation induced by functional activin protein,
suggesting that dysfunction of ER caused a failure in activin/nodal
processing and/or secretion. The observation that activin protein
renders mesoderm formation under ER stress strengthens the role of
activin/nodal for mesoderm induction. The results underline the functional
significance of ER homeostasis in germ layer formation during Xenopus
embryogenesis. Developmental Dynamics 236:2844–2851, 2007 © 2007
Wiley-Liss, Inc.},
issn = {1097-0177},
keywords = {tunicamycin, activin/nodal, cap assay, endoplasmic reticulum, Xenopus
laevis},
publisher = {Wiley-Liss, Inc.},
url = {http://dx.doi.org/10.1002/dvdy.21299}
}
@ARTICLE{Yuan2008,
author = {Yuan, Li and Cao, Ying and Oswald, Franz and Knöchel, Walter},
title = {IRE1[beta] is required for mesoderm formation in Xenopus embryos},
journal = {Mechanisms of Development},
year = {2008},
volume = {125},
pages = {207--222},
number = {3-4},
month = mar,
abstract = {IRE1 is an atypical serine/threonine kinase transmembrane protein
with RNase activity. In the unfolded protein response (UPR), they
function as proximal sensor of the unfolded proteins in the endoplasmic
reticulum (ER). Upon activation by ER stress, IRE1 performs an unconventional
cytoplasmic splicing of XBP1 pre-mRNA and thus allows the synthesis
of active XBP1, which activates UPR target genes to restore the homeostasis
of the ER. IRE1/XBP1 signaling is hence essential for UPR but its
function during embryogenesis is yet unknown. The transcripts of
the two isoforms of IRE1 in Xenopus, xIRE1[alpha] and xIRE1[beta]
are differentially expressed during embryogenesis. We found that
xIRE1[beta] is sufficient for cytoplasmic splicing of xXBP1 pre-mRNA.
Although gain of xIRE1[beta] function had no significant effect on
Xenopus embryogenesis, overexpression of both, xIRE1[beta] and xXBP1
pre-mRNA, inhibits activin A induced mesoderm formation, suggesting
that an enhanced activity of the IRE1/XBP1 pathway represses mesoderm
formation. Surprisingly, while loss of XBP1 function promotes mesoderm
formation, the loss of IRE1[beta] function led to a reduction of
mesoderm formation, probably by action of IRE1 being different from
the IRE1/XBP1 pathway. Therefore, both gain and loss of function
studies demonstrate that IRE1 is required for mesoderm formation
in Xenopus embryos.},
issn = {0925-4773},
keywords = {IRE1, XBP1, Mesoderm, Xenopus laevis},
url = {http://www.sciencedirect.com/science/article/B6T9H-4R9GGRS-1/2/5c76f4dcb64f2c5d5e19a069d81cc284}
}
@ARTICLE{Yuan2012,
author = {Min Yuan and Yonggang Zhu and Xinhui Lou and Chen Chen and Gang Wei
and Minbo Lan and Jianlong Zhao},
title = {Sensitive label-free oligonucleotide-based microfluidic detection
of mercury (II) ion by using exonuclease I},
journal = {Biosensors and Bioelectronics},
year = {2012},
volume = {31},
pages = {330 - 336},
number = {1},
abstract = {Mercury is a highly toxic metal that can cause significant harm to
humans and aquatic ecosystems. This paper describes a novel approach
for mercury (Hg2+) ion detection by using label-free oligonucleotide
probes and Escherichia coli exonuclease I (Exo I) in a microfluidic
electrophoretic separated platform. Two single-stranded DNAs (ssDNA)
TT-21 and TT-44 with 7 Thymine–Thymine mispairs are employed to
capture mercury ions. Due to the coordination structure of T–Hg2+–T,
these ssDNAs are folded into hairpin-like double-stranded DNAs (dsDNA)
which are more difficult to be digested by Exo I, as confirmed by
polyacrylamide gel electrophoresis (PAGE) analysis. A series of microfluidic
capillary electrophoretic separation studies are carried out to investigate
the effect of Exo I and mercury ion concentrations on the detected
fluorescence intensity. This method has demonstrated a high sensitivity
of mercury ion detection with the limit of detection around 15 nM
or 3 ppb. An excellent selectivity of the probe for mercury
ions over five interference ions Fe3+, Cd2+, Pb2+, Cu2+ and Ca2+
is also revealed. This method could potentially be used for mercury
ion detection with high sensitivity and reliability.},
doi = {10.1016/j.bios.2011.10.043},
issn = {0956-5663},
keywords = {Mercury ions},
url = {http://www.sciencedirect.com/science/article/pii/S0956566311007317}
}
@ARTICLE{Yuan2007b,
author = {Yuan, Wenlin and Payton, Jacqueline E. and Holt, Matthew S. and Link,
Daniel C. and Watson, Mark A. and DiPersio, John F. and Ley, Timothy
J.},
title = {Commonly dysregulated genes in murine APL cells},
journal = {Blood},
year = {2007},
volume = {109},
pages = {961--970},
number = {3},
month = feb,
abstract = {To identify genes that are commonly dysregulated in a murine model
of acute promyelocytic leukemia (APL), we first defined gene expression
patterns during normal murine myeloid development; serial gene expression
profiling studies were performed with primary murine hematopoietic
progenitors that were induced to undergo myeloid maturation in vitro
with G-CSF. Many genes were reproducibly expressed in restricted
developmental "windows," suggesting a structured hierarchy of expression
that is relevant for the induction of developmental fates and/or
differentiated cell functions. We compared the normal myeloid developmental
transcriptome with that of APL cells derived from mice expressing
PML-RAR{alpha} under control of the murine cathepsin G locus. While
many promyelocyte-specific genes were highly expressed in all APL
samples, 116 genes were reproducibly dysregulated in many independent
APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this
set of commonly dysregulated genes was expressed normally in preleukemic,
early myeloid cells from the same mouse model, suggesting that dysregulation
occurs as a "downstream" event during disease progression. These
studies suggest that the genetic events that lead to APL progression
may converge on common pathways that are important for leukemia pathogenesis.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/3/961}
}
@ARTICLE{Yuan2010,
author = {Yuan, Xiaolian and Jonker, Martijs J. and de Wilde, Jillian and Verhoef,
Aart and Wittink, Floyd R.A. and van Benthem, Jan and Bessems, Jos
G. and Hakkert, Betty C. and Kuiper, Raoul V. and van Steeg, Harry
and Breit, Timo M. and Luijten, Mirjam},
title = {Finding maximal transcriptome differences between reprotoxic and
non-reprotoxic phthalate responses in rat testis},
journal = {J. Appl. Toxicol.},
year = {2010},
pages = {n/a--n/a},
abstract = {Abstract The chemical legislation of the EU, Registration, Evaluation,
and Authorization of Chemicals (REACH), stipulates that about 30 000
chemical substances are to be assessed on their possible risks. Toxicological
evaluation of these compounds will at least partly be based on animal
testing. In particular, the assessment of reproductive toxicity is
a very complicated, time-consuming and animal-demanding process.
Introducing microarray-based technologies can potentially refine
in vivo toxicity testing. If compounds of a distinct chemical class
induce reproducible gene-expression responses with a recognizable
overlap, these gene-expression signatures may indicate intrinsic
features of certain compounds, including specific toxicity. In the
present study, we have set out the first steps towards this approach
for the reproductive toxicity of phthalates. Male rats were treated
with a single dose of either reprotoxic or non-reprotoxic phthalates,
and were analyzed 24 h afterwards. Subsequently, histopathological
and gene-expression profiling analyses were performed. Despite ambiguous
histopathological observations, we were able to identify genes with
differential expression profiles between the reprotoxic phthalates
and the non-reprotoxic counterparts. This shows that differences
in gene-expression profiles, indicative of the type of exposure,
may be detected earlier, or at lower doses, than classical pathological
endpoints. These findings are promising for ‘early warning’ biomarker
analyses and for using toxicogenomics in a category approach. Ultimately,
this could lead to a more cost-effective approach for prioritizing
the toxicity testing of large numbers of chemicals in a short period
of time in hazard assessment of chemicals, which is one of the objectives
of the REACH chemical legislation. Copyright © 2010 John Wiley &
Sons, Ltd.},
issn = {1099-1263},
keywords = {phthalates, reproductive toxicity, microarray analysis, rat testis,
risk assessment},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jat.1601}
}
@ARTICLE{Yue2001,
author = {Yue, Huibin and Eastman, P. Scott and Wang, Bruce B. and Minor, James
and Doctolero, Michael H. and Nuttall, Rachel L. and Stack, Robert
and Becker, John W. and Montgomery, Julie R. and Vainer, Marina and
Johnston, Rick},
title = {An evaluation of the performance of cDNA microarrays for detecting
changes in global mRNA expression},
journal = {Nucleic Acids Res.},
year = {2001},
volume = {29},
pages = {e41--},
number = {8},
month = apr,
abstract = {The cDNA microarray is one technological approach that has the potential
to accurately measure changes in global mRNA expression levels. We
report an assessment of an optimized cDNA microarray platform to
generate accurate, precise and reliable data consistent with the
objective of using microarrays as an acquisition platform to populate
gene expression databases. The study design consisted of two independent
evaluations with 70 arrays from two different manufactured lots and
used three human tissue sources as samples: placenta, brain and heart.
Overall signal response was linear over three orders of magnitude
and the sensitivity for any element was estimated to be 2 pg mRNA.
The calculated coefficient of variation for differential expression
for all non-differentiated elements was 12-14% across the entire
signal range and did not vary with array batch or tissue source.
The minimum detectable fold change for differential expression was
1.4. Accuracy, in terms of bias (observed minus expected differential
expression ratio), was less than 1 part in 10 000 for all non-differentiated
elements. The results presented in this report demonstrate the reproducible
performance of the cDNA microarray technology platform and the methods
provide a useful framework for evaluating other technologies that
monitor changes in global mRNA expression.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/29/8/e41}
}
@ARTICLE{Yuen2001,
author = {Yuen, Po Ki and Kricka, Larry J. and Fortina, Paolo and Panaro, Nicholas
J. and Sakazume, Taku and Wilding, Peter},
title = {Microchip Module for Blood Sample Preparation and Nucleic Acid Amplification
Reactions},
journal = {Genome Res.},
year = {2001},
volume = {11},
pages = {405--412},
number = {3},
month = mar,
abstract = {A computer numerical control-machined plexiglas-based microchip module
was designed and constructed for the integration of blood sample
preparation and nucleic acid amplification reactions. The microchip
module is comprised of a custom-made heater-cooler for thermal cycling,
a series of 254 {micro}m x 254 {micro}m microchannels for transporting
human whole blood and reagents in and out of an 8-9 {micro}L dual-purpose
(cell isolation and PCR) glass-silicon microchip. White blood cells
were first isolated from a small volume of human whole blood (<3
{micro}L) in an integrated cell isolation-PCR microchip containing
a series of 3.5-{micro}m feature-sized "weir-type" filters, formed
by an etched silicon dam spanning the flow chamber. A genomic target,
a region in the human coagulation Factor V gene (226-bp), was subsequently
directly amplified by microchip-based PCR on DNA released from white
blood cells isolated on the filter section of the microchip mounted
onto the microchip module. The microchip module provides a convenient
means to simplify nucleic acid analyses by integrating two key steps
in genetic testing procedures, cell isolation and PCR and promises
to be adaptable for additional types of integrated assays.},
url = {http://genome.cshlp.org/cgi/content/abstract/11/3/405}
}
@ARTICLE{Yuen2006,
author = {Yuen, Peter S. T. and Jo, Sang-Kyung and Holly, Mikaela K. and Hu,
Xuzhen and Star, Robert A.},
title = {Ischemic and nephrotoxic acute renal failure are distinguished by
their broad transcriptomic responses},
journal = {Physiol Genomics},
year = {2006},
volume = {25},
pages = {375--386},
number = {3},
month = may,
abstract = {Acute renal failure (ARF) has a high morbidity and mortality. In animal
ARF models, effective treatments must be administered before or shortly
after the insult, limiting their clinical potential. We used microarrays
to identify early biomarkers that distinguish ischemic from nephrotoxic
ARF or biomarkers that detect both injury types. We compared rat
kidney transcriptomes at 2 and 8 h after ischemia/reperfusion and
after mercuric chloride. Quality control and statistical analyses
were necessary to normalize microarrays from different lots, eliminate
outliers, and exclude unaltered genes. Principal component analysis
revealed distinct ischemic and nephrotoxic trajectories and clear
array groupings. Therefore, we used supervised analysis, t-tests,
and fold changes to compile gene lists for each group, exclusive
or nonexclusive, alone or in combination. There was little network
connectivity, even in the largest group. Some microarray-identified
genes were validated by TaqMan assay, ruling out artifacts. Western
blotting confirmed that heme oxygenase-1 (HO-1) and activating transcription
factor-3 (ATF3) proteins were upregulated; however, unexpectedly,
their localization changed within the kidney. HO-1 staining shifted
from cortical (early) to outer stripe of the outer medulla (late),
primarily in detaching cells, after mercuric chloride but not ischemia/reperfusion.
ATF3 staining was similar, but with additional early transient expression
in the outer stripe after ischemia/reperfusion. We conclude that
microarray-identified genes must be evaluated not only for protein
levels but also for anatomical distribution among different zones,
nephron segments, or cell types. Although protein detection reagents
are limited, microarray data lay a rich foundation to explore biomarkers,
therapeutics, and the pathophysiology of ARF.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/25/3/375}
}
@ARTICLE{Yukhananov2008,
author = {Yukhananov, Rustam and Kissin, Igor},
title = {Persistent changes in spinal cord gene expression after recovery
from inflammatory hyperalgesia: A preliminary study on pain memory},
journal = {BMC Neuroscience},
year = {2008},
volume = {9},
pages = {32},
number = {1},
abstract = {BACKGROUND:Previous studies found that rats subjected to carrageenan
injection develop hyperalgesia, and despite complete recovery in
several days, they continue to have an enhanced hyperalgesic response
to a new noxious challenge for more than 28d. The study's aim was
to identify candidate genes that have a role in the formation of
the long-term hyperalgesia-related imprint in the spinal cord. This
objective was undertaken with the understanding that the long-lasting
imprint of acute pain in the central nervous system may contribute
to the transition of acute pain to chronicity.RESULTS:To analyze
changes in gene expression when carrageenan-induced hyperalgesia
has disappeared but propensity for the enhanced hyperalgesic response
is still present, we determined the gene expression profile using
oligo microarray in the lumbar part of the spinal cord in three groups
of rats: 28d after carrageenan injection, 24h after injection (the
peak of inflammation), and with no injection (control group). Out
of 17,000 annotated genes, 356 were found to be differentially expressed
compared with the control group at 28d, and 329 at 24h after carrageenan
injection (both groups at p < 0.01). Among differentially expressed
genes, 67 (39 in 28d group) were identified as being part of pain-related
pathways, altered in different models of pain, or interacting with
proteins involved in pain-related pathways. Using gene ontology (GO)
classification, we have identified 3 functional classes deserving
attention for possible association with pain memory: They are related
to cell-to-cell interaction, synaptogenesis, and neurogenesis.CONCLUSION:Despite
recovery from inflammatory hyperalgesia, persistent changes in spinal
cord gene expression may underlie the propensity for the enhanced
hyperalgesic response. We suggest that lasting changes in expression
of genes involved in the formation of new synapses and neurogenesis
may contribute to the transition of acute pain to chronicity.},
doi = {10.1186/1471-2202-9-32},
issn = {1471-2202},
pubmedid = {18366630},
url = {http://www.biomedcentral.com/1471-2202/9/32}
}
@ARTICLE{Yun2010,
author = {Yun, Jun-Won and Kim, Chae-Wook and Bae, Il-Hong and Park, Young-Ho
and Chung, Jin-Ho and Lim, Kyung-Min and Kang, Kyung-Sun},
title = {Expression levels of pituitary tumor transforming 1 and glutathione-S-transferase
theta 3 are associated with the individual susceptibility to d-galactosamine-induced
hepatotoxicity},
journal = {Toxicology and Applied Pharmacology},
year = {2010},
volume = {242},
pages = {91--99},
number = {1},
month = jan,
issn = {0041-008X},
keywords = {Individual variation, Hepatotoxicity, Toxicogenomics, Microarray analysis,
d-galactosamine, Prediction},
url = {http://www.sciencedirect.com/science/article/B6WXH-4XC57DJ-1/2/b7ecf8d832c0e3678598fdb8c1e3f819}
}
@ARTICLE{Yun2009,
author = {Yun, Jun-Won and Kim, Chae-Wook and Bae, Il-Hong and Park, Young-Ho
and Chung, Jin-Ho and Lim, Kyung-Min and Kang, Kyung-Sun},
title = {Determination of the key innate genes related to individual variation
in carbon tetrachloride-induced hepatotoxicity using a pre-biopsy
procedure},
journal = {Toxicology and Applied Pharmacology},
year = {2009},
volume = {239},
pages = {55--63},
number = {1},
month = aug,
issn = {0041-008X},
keywords = {Individual variation, Hepatotoxicity, Toxicogenomics, Microarray analysis,
Carbon tetrachloride},
url = {http://www.sciencedirect.com/science/article/B6WXH-4WCTWM9-1/2/346ce65b39ebf6228d546471b749a44e}
}
@ARTICLE{Yung2004,
author = {Yung, Christina K. and Halperin, Victoria L. and Tomaselli, Gordon
F. and Winslow, Raimond L.},
title = {Gene expression profiles in end-stage human idiopathic dilated cardiomyopathy:
altered expression of apoptotic and cytoskeletal genes},
journal = {Genomics},
year = {2004},
volume = {83},
pages = {281--297},
number = {2},
month = feb,
abstract = {Dilated cardiomyopathy is now the leading cause of cardiovascular
morbidity and mortality. While the molecular basis of this disease
remains uncertain, evidence is emerging that gene expression profiles
of left ventricular myocardium isolated from failing versus nonfailing
patients differ dramatically. In this study, we use high-density
oligonucleotide microarrays with ~22,000 probes to characterize differences
in the expression profiles further. To facilitate interpretation
of experimental data, we evaluate algorithms for normalization of
hybridization data and for computation of gene expression indices
using a control spike-in data set. We then use these methods to identify
statistically significant changes in the expression levels of genes
not previously implicated in the molecular phenotype of heart failure.
These regulated genes take part in diverse cellular processes, including
transcription, apoptosis, sarcomeric and cytoskeletal function, remodeling
of the extracellular matrix, membrane transport, and metabolism.},
issn = {0888-7543},
keywords = {Heart failure, Dilated cardiomyopathy, Cardiovascular genomics, Gene
expression, Oligonucleotide microarray},
url = {http://www.sciencedirect.com/science/article/B6WG1-49P82WN-1/2/79d05f2d17ab78a280618a4e9763e4b0}
}
@ARTICLE{Yusuf2010,
author = {Yusuf, Isharat and Kageyama, Robin and Monticelli, Laurel and Johnston,
Robert J. and DiToro, Daniel and Hansen, Kyle and Barnett, Burton
and Crotty, Shane},
title = {Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent
on Signaling Lymphocytic Activation Molecule Receptor (CD150)},
journal = {J. Immunol.},
year = {2010},
volume = {185},
pages = {190--202},
number = {1},
month = jul,
abstract = {CD4 T cell help is critical for the generation and maintenance of
germinal centers (GCs), and T follicular helper (TFH) cells are the
CD4 T cell subset required for this process. Signaling lymphocytic
activation molecule (SLAM)-associated protein (SAP [SH2D1A]) expression
in CD4 T cells is essential for GC development. However, SAP-deficient
mice have only a moderate defect in TFH differentiation, as defined
by common TFH surface markers. CXCR5+ TFH cells are found within
the GC, as well as along the boundary regions of T/B cell zones.
In this study, we show that GC-associated T follicular helper (GC
TFH) cells can be identified by their coexpression of CXCR5 and the
GL7 epitope, allowing for phenotypic and functional analysis of TFH
and GC TFH populations. GC TFH cells are a functionally discrete
subset of further polarized TFH cells, with enhanced B cell help
capacity and a specialized ability to produce IL-4 in a TH2-independent
manner. Strikingly, SAP-deficient mice have an absence of the GC
TFH cell subset and SAP- TFH cells are defective in IL-4 and IL-21
production. We further demonstrate that SLAM (Slamf1, CD150), a surface
receptor that uses SAP signaling, is specifically required for IL-4
production by GC TFH cells. GC TFH cells require IL-4 and -21 production
for optimal help to B cells. These data illustrate complexities of
SAP-dependent SLAM family receptor signaling, revealing a prominent
role for SLAM receptor ligation in IL-4 production by GC CD4 T cells
but not in TFH cell and GC TFH cell differentiation.},
url = {http://www.jimmunol.org/cgi/content/abstract/185/1/190}
}
@ARTICLE{Zaas2010,
author = {Zaas, Aimee K. and Aziz, Hamza and Lucas, Joseph and Perfect, John
R. and Ginsburg, Geoffrey S.},
title = {Blood Gene Expression Signatures Predict Invasive Candidiasis},
journal = {Science Translational Medicine},
year = {2010},
volume = {2},
pages = {21ra17--},
number = {21},
month = mar,
abstract = {Candidemia is the fourth most common bloodstream infection, with Candida
albicans being the most common causative species. Success in reducing
the associated morbidity and mortality has been limited by the inadequacy
and time delay of currently available diagnostic modalities. Focusing
on host response to infection, we used a murine model to develop
a blood gene expression signature that accurately classified mice
with candidemia and distinguished candidemia from Staphylococcus
aureus bacteremia. Validation of the signature was achieved in an
independent cohort of mice. Genes represented in the signature have
known associations with host defense against Candida and other microorganisms.
Our results demonstrate a temporal pattern of host molecular responses
that distinguish candidemia from S. aureus-induced bacteremia and
establish a novel paradigm for infectious disease diagnosis.},
url = {http://stm.sciencemag.org/cgi/content/abstract/2/21/21ra17}
}
@ARTICLE{Zaborin2009,
author = {Zaborin, Alexander and Romanowski, Kathleen and Gerdes, Svetlana
and Holbrook, Christopher and Lepine, Francois and Long, Jason and
Poroyko, Valeriy and Diggle, Stephen P. and Wilke, Andreas and Righetti,
Karima and Morozova, Irina and Babrowski, Trissa and Liu, Donald
C. and Zaborina, Olga and Alverdy, John C.},
title = {Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa
PAO1},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {6327--6332},
number = {15},
month = apr,
abstract = {During host injury, Pseudomonas aeruginosa can be cued to express
a lethal phenotype within the intestinal tract reservoir--a hostile,
nutrient scarce environment depleted of inorganic phosphate. Here
we determined if phosphate depletion activates a lethal phenotype
in P. aeruginosa during intestinal colonization. To test this, we
allowed Caenorhabditis elegans to feed on lawns of P. aeruginosa
PAO1 grown on high and low phosphate media. Phosphate depletion caused
PAO1 to kill 60% of nematodes whereas no worms died on high phosphate
media. Unexpectedly, intense redness was observed in digestive tubes
of worms before death. Using a combination of transcriptome analyses,
mutants, and reporter constructs, we identified 3 global virulence
systems that were involved in the "red death" response of P. aeruginosa
during phosphate depletion; they included phosphate signaling (PhoB),
the MvfR-PQS pathway of quorum sensing, and the pyoverdin iron acquisition
system. Activation of all 3 systems was required to form a red colored
PQS+Fe3+ complex which conferred a lethal phenotype in this model.
When pyoverdin production was inhibited in P. aeruginosa by providing
excess iron, red death was attenuated in C. elegans and mortality
was decreased in mice intestinally inoculated with P. aeruginosa.
Introduction of the red colored PQS+Fe3+ complex into the digestive
tube of C. elegans or mouse intestine caused mortality associated
with epithelial disruption and apoptosis. In summary, red death in
C. elegans reveals a triangulated response between PhoB, MvfR-PQS,
and pyoverdin in response to phosphate depletion that activates a
lethal phenotype in P. aeruginosa.},
url = {http://www.pnas.org/cgi/content/abstract/106/15/6327}
}
@ARTICLE{Zacharias2010,
author = {Zacharias, William J. and Li, Xing and Madison, Blair B. and Kretovich,
Katherine and Kao, John Y. and Merchant, Juanita L. and Gumucio,
Deborah L.},
title = {Hedgehog Is an Anti-Inflammatory Epithelial Signal for the Intestinal
Lamina Propria},
journal = {Gastroenterology},
year = {2010},
volume = {138},
pages = {2368--2377.e4},
number = {7},
month = jun,
abstract = {Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal
intestinal organogenesis, and emerging data implicate the Hh pathway
in inflammatory signaling in the adult colon. Here, we investigated
the effects of chronic Hh inhibition in vivo and profiled molecular
pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
The progression of inflammatory disease was characterized in a bi-transgenic
mouse model of chronic Hh inhibition (VFHhip). In parallel, microarray
and bioinformatic analyses (Gene Ontology terms overrepresentation
analysis, hierarchical clustering, and MeSH term filtration) were
performed on isolated cultured intestinal mesenchyme acutely exposed
to Hh ligand. Six- to 10-month-old VFHhip animals exhibited villus
smooth muscle loss and subsequent villus atrophy. Areas of villus
loss became complicated by spontaneous inflammation and VFHhip animals
succumbed to wasting and death. Phenotypic similarities were noted
between the VFHhip phenotype and human inflammatory disorders, especially
human celiac disease. Microarray analysis revealed that inflammatory
pathways were acutely activated in intestinal mesenchyme cultured
in the absence of epithelium, and the addition of Hh ligand alone
was sufficient to largely reverse this inflammatory response within
24 hours. Hh ligand is a previously unrecognized anti-inflammatory
epithelial modulator of the mesenchymal inflammatory milieu. Acute
modulation of Hh signals results in changes in inflammatory pathways
in intestinal mesenchyme, while chronic inhibition of Hh signaling
in adult animals leads to spontaneous intestinal inflammation and
death. Regulation of epithelial Hh signaling may be an important
mechanism to modulate tolerogenic versus proinflammatory signaling
in the small intestine.},
issn = {0016-5085},
keywords = {Hedgehog Signaling, Inflammatory Bowel Disease, Celiac Disease, Myeloid
Cells, Hh, Hedgehog, IBD, inflammatory bowel disease, Ig, immunoglobulin,
Ihh, Indian Hedgehog, IL, interleukin, Shh, Sonic Hedgehog, TSLP,
thymic stromal lymphopoietin, VFHhip, 12.4KVil-Cre x 12.4KVil-flox-LacZ-flox-Hhip},
publisher = {W.B. Saunders},
refid = {S0016-5085(10)00330-6},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0016508510003306?showall=true}
}
@ARTICLE{Zackova2010,
author = {Zackova, Marketa and Lopotova, Tereza and Ondrackova, Zuzana and
Klamova, Hana and Moravcova, Jana},
title = {In Vitro Sensitivity to Tyrosine Kinase Inhibitors Is One of Possible
Predictive Parameters for Therapy Switch In Patients with Chronic
Myeloid Leukemia},
journal = {Blood (ASH Annual Meeting Abstracts)},
year = {2010},
volume = {116},
pages = {2747--},
number = {21},
month = nov,
abstract = {Abstract 2747 BackroundTyrosine kinase inhibitors (TKI) are very effective
in chronic myeloid leukemia (CML) suppression, however, the problem
with development of resistance in some patients exists. It is necessary
to find optimal methods for therapy response prediction and for detection
of resistance. Many studies on the resistance to imatinib therapy
were performed on cell lines or model systems. However, these systems
are not fully consistent with CML situation in vivo. Sensitivity
to imatinib and its predictivity to molecular response in patients
with de novo CML were tested in vitro on patients' leukocytes by
White et al. [Blood 2005; 106: 2520]. They found that IC50 values
could be predictive mainly in patients with low Sokal score. Aims
To optimize in vitro method for evaluation of patients' sensitivity
to various TKIs and to test its predictivity for molecular response
in therapy and/or after therapy change. MethodsThe sensitivity to
TKIs: imatinib, nilotinib and dasatinib were studied on leukocytes
isolated from CML patients at diagnosis and various responses to
treatment. Cell lines were used as controls. Isolated leukocytes/cell
lines were cultivated with/without TKIs. Optimization of cultivation
was performed on cell lines (ML-2, K562, CML-T2, JURL-MK1) and on
leukocytes from CML newly diagnosed patients (15) and healthy donors
(6). Various incubation times (4, 24, 48 and 72h) were tested. Concentrations
of TKI were used in values near to physiological levels: 2 -3 concentrations
for each inhibitor (1uM, 10uM imatinib, 0,5uM and 2uM nilotinib and
1nM, 10nM and 100nM dasatinib). In given time-points the cells were
harvested and lysed for protein and mRNA analyses. Sensitivity to
TKIs was tested by BCR-ABL kinase inhibition - via Crkl phosphorylation
(western blots) and also by WT1 transcript level kinetics [Cilloni
et al, Cancer 2004; 101: 979]. Quality of cultivation was tested
by apoptosis level (RNA degradation, Annexin staining - Agilent Bioanalyzer
2100). ResultsWe found 48 h to be the optimal time for in vitro cultivation.
This time was long enough to see TKIs dependent changes on protein
as well as mRNA level. At this time the intensity of apoptosis was
relatively low and did not influence results. The predictive ability
of cultivation with TKIs was tested on patients at diagnosis (15),
with optimal (5) and suboptimal response (5) and patient with therapy
failure (13). The disease state of all patients was further monitored
in range from 6 to 21 months (median 12 months) after cultivation.
Mostly all of newly diagnosed patients were in vitro sensitive to
all three TKIs, 10 of them achieved MMR (median 7 months, range 5
- 16) on imatinib. In patients with resistance to imanitib therapy
the good sensitivity to one of 2nd generation TKI on in vitro tests
represented the good response to this inhibitor, 4 patients from
10 on dasatinib achieved MMR (within 4 months), the other responded
to therapy with continual decrease of BCR-ABL transcript level. Thus,
the cultivation test can help with the therapy switch. However, the
prognosis of patients with additive chromosomal aberration was poor
even if they were sensitive to TKIs in vitro. Only one of 3 patients
with 8 trisomy sensitive to dasatinib in vitro achieved MMR at 4th
month after starting of dasatinib. Two patients with T315I were not
sensitive to any of TKIs in vitro and in vivo, as it was expected.
We continue to follow up of all patients. In conclusion, the results
from in vitro cultivations of patients' leukocytes with TKIs can
help with the choice of efficient inhibitor for individual patient's
therapy, however, it is necessary to take into consideration the
results of cytogenetic analyses of patients and other factors influencing
CML. Supported by MZOUHKT2005. DisclosuresNo relevant conflicts of
interest to declare.},
url = {http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/2747}
}
@ARTICLE{Zagordi2010,
author = {Zagordi, Osvaldo and Klein, Rolf and Daumer, Martin and Beerenwinkel,
Niko},
title = {Error correction of next-generation sequencing data and reliable
estimation of HIV quasispecies},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {7400--7409},
number = {21},
month = nov,
abstract = {Next-generation sequencing technologies can be used to analyse genetically
heterogeneous samples at unprecedented detail. The high coverage
achievable with these methods enables the detection of many low-frequency
variants. However, sequencing errors complicate the analysis of mixed
populations and result in inflated estimates of genetic diversity.
We developed a probabilistic Bayesian approach to minimize the effect
of errors on the detection of minority variants. We applied it to
pyrosequencing data obtained from a 1.5-kb-fragment of the HIV-1
gag/pol gene in two control and two clinical samples. The effect
of PCR amplification was analysed. Error correction resulted in a
two- and five-fold decrease of the pyrosequencing base substitution
rate, from 0.05% to 0.03% and from 0.25% to 0.05% in the non-PCR
and PCR-amplified samples, respectively. We were able to detect viral
clones as rare as 0.1% with perfect sequence reconstruction. Probabilistic
haplotype inference outperforms the counting-based calling method
in both precision and recall. Genetic diversity observed within and
between two clinical samples resulted in various patterns of phenotypic
drug resistance and suggests a close epidemiological link. We conclude
that pyrosequencing can be used to investigate genetically diverse
samples with high accuracy if technical errors are properly treated.},
comment = {10.1093/nar/gkq655},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/21/7400}
}
@ARTICLE{Zagranichnaya2005,
author = {Zagranichnaya, Tatiana K. and Wu, Xiaoyan and Danos, Arpad M. and
Villereal, Mitchel L.},
title = {Gene expression profiles in HEK-293 cells with low or high store-operated
calcium entry: can regulatory as well as regulated genes be identified?},
journal = {Physiol Genomics},
year = {2005},
volume = {21},
pages = {14--33},
number = {1},
month = mar,
abstract = {Gene expression profiles were generated using cDNA microarray technology
for clones of human embryonic kidney (HEK)-293 cells selected to
have either high or low levels of store-operated Ca2+ entry (SOCE).
For five high clones, three low clones, and control HEK-293 cells,
duplicate Affymetrix U133A human gene arrays were run after extraction
of total RNA from cells growing in the presence of serum. Of the
[~]22,000 genes represented on the microarray, 58 genes had readings
at least twofold higher, while 32 genes had readings at least twofold
lower, in all five high SOCE clones compared with control HEK-293
cells. In the low SOCE clones, 92 genes had readings at least twofold
higher, while 58 genes had readings at least twofold lower, than
in HEK-293 cells. Microarray results were confirmed for 18 selected
genes by real-time RT-PCR analysis; for six of those genes, predicted
changes in the low SOCE clone were confirmed by an alternative method,
monitoring mRNA levels in HEK-293 with SOCE decreased by expression
of small interfering (si)RNA to canonical transient receptor potential
protein-1. Genes regulated by SOCE are involved in signal transduction,
transcription, apoptosis, metabolism, and membrane transport. These
data provide insight into the physiological role of SOCE. In addition,
a potential regulator of SOCE, insulin receptor substrate (IRS)-2,
has been identified. A reduction of IRS-2 levels by siRNA methods
in two high clones dramatically reduced SOCE, whereas overexpression
of IRS-2 in a low SOCE clone elevated SOCE.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/21/1/14}
}
@ARTICLE{Zagrobelny2009,
author = {Zagrobelny, Mika and Scheibye-Alsing, Karsten and Jensen, Niels and
Møller, Birger and Gorodkin, Jan and Bak, Søren},
title = {454 pyrosequencing based transcriptome analysis of Zygaena filipendulae
with focus on genes involved in biosynthesis of cyanogenic glucosides},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {574},
number = {1},
abstract = {BACKGROUND:An essential driving component in the co-evolution of plants
and insects is the ability to produce and handle bioactive compounds.
Plants produce bioactive natural products for defense, but some insects
detoxify and/or sequester the compounds, opening up for new niches
with fewer competitors. To study the molecular mechanism behind the
co-adaption in plant-insect interactions, we have investigated the
interactions between Lotus corniculatus and Zygaena filipendulae.
They both contain cyanogenic glucosides which liberate toxic hydrogen
cyanide upon breakdown. Moths belonging to the Zygaena family are
the only insects known, able to carry out both de novo biosynthesis
and sequestration of the same cyanogenic glucosides as those from
their feed plants. The biosynthetic pathway for cyanogenic glucoside
biosynthesis in Z. filipendulae proceeds using the same intermediates
as in the well known pathway from plants, but none of the enzymes
responsible have been identified. A genomics strategy founded on
454 pyrosequencing of the Z. filipendulae transcriptome was undertaken
to identify some of these enzymes in Z. filipendulae.RESULTS:Comparisons
of the Z. filipendulae transcriptome with the sequenced genomes of
Bombyx mori, Drosophila melanogaster, Tribolium castaneum, Apis mellifera
and Anopheles gambiae indicate a high coverage of the Z. filipendulae
transcriptome. 11% of the Z. filipendulae transcriptome sequences
were assigned to Gene Ontology categories. Candidate genes for enzymes
functioning in the biosynthesis of cyanogenic glucosides (cytochrome
P450 and family 1 glycosyltransferases) were identified based on
sequence length, number of copies and presence/absence of close homologs
in D. melanogaster, B. mori and the cyanogenic butterfly Heliconius.
Examination of biased codon usage, GC content and selection on gene
candidates support the notion of cyanogenesis as an "old" trait within
Ditrysia, as well as its origins being convergent between plants
and insects.CONCLUSION:Pyrosequencing is an attractive approach to
gain access to genes in the biosynthesis of bio-active natural products
from insects and other organisms, for which the genome sequence is
not known. Based on analysis of the Z. filipendulae transcriptome,
promising gene candidates for biosynthesis of cyanogenic glucosides
was identified, and the suitability of Z. filipendulae as a model
system for cyanogenesis in insects is evident.},
doi = {10.1186/1471-2164-10-574},
issn = {1471-2164},
pubmedid = {19954531},
url = {http://www.biomedcentral.com/1471-2164/10/574}
}
@ARTICLE{Zaharik2007,
author = {Zaharik, Michelle L. and Nayar, Tarun and White, Rick and Ma, Caixia
and Vallance, Bruce A. and Straka, Nadine and Jiang, Xiaozhou and
Rey-Ladino, Jose and Shen, Caixia and Brunham, Robert C.},
title = {Genetic profiling of dendritic cells exposed to live- or ultraviolet-irradiated
Chlamydia muridarum reveals marked differences in CXC chemokine profiles},
journal = {Immunology},
year = {2007},
volume = {120},
pages = {160--172},
number = {2},
abstract = {Summary Chlamydia trachomatis is a major cause of sexually transmitted
disease worldwide for which an effective vaccine is being actively
pursued. Current vaccine efforts will be aided by elucidating the
interaction between Chlamydia and dendritic cells (DCs). Protective
immunity appears to develop slowly following natural infection in
humans, and early vaccine trials using inactivated C. trachomatis
resulted in partial, short-lived protection with possible enhanced
inflammatory pathology during re-infection. Thus, immunity following
natural infection with live chlamydia may differ fundamentally from
immune responses induced by immunization with inactivated chlamydia.
We explored this conjecture by studying the response of DCs exposed
to either viable or inactivated [ultraviolet (UV) –irradiated]
chlamydia elementary bodies (EBs; designated as Live-EB and UV-EB,
respectively) using Affymetrix GeneChip microarrays. Thirty-one immunologically
characterized genes were differentially expressed by DCs following
exposure to Live-EB or UV-EB, including two glutamic acid–leucine–arginine
cysteine–X–cysteine (ELR CXC) neutrophil chemoattractant chemokines,
Cxcl1 (KC), and Cxcl2 (MIP-2). Up-regulation of these genes by Live-EB
as compared to UV-EB was verified by quantitative reverse transcription–polymerase
chain reaction and increased chemokine secretion was confirmed by
enzyme-linked immunosorbent assay both in vitro and in vivo. Immunofluorescence
and fluorescence-activated cell sorter analysis of chlamydia-infected
lung tissue confirmed that Live-EB but not UV-EB induced significant
DC and neutrophil infiltration during infection. These observations
demonstrate that the development of an antichlamydial immune response
is dramatically influenced by chlamydial viability. This has implications
as to why early inactivated chlamydial vaccines were ineffective
and suggests that new vaccine design efforts may benefit from in
vitro DC screening for ELR chemokine expression profiles.},
issn = {1365-2567},
keywords = {Chlamydia, CXC chemokine, Dendritic cell, Vaccine development},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2006.02488.x}
}
@ARTICLE{Zaher2008,
author = {Zaher, Hani and zu Schwabedissen, Henriette E. Meyer and Tirona,
Rommel G. and Cox, Melissa L. and Obert, Leslie A. and Agrawal, Nidhi
and Palandra, Joe and Stock, Jeffrey L. and Kim, Richard B. and Ware,
Joseph A.},
title = {Targeted Disruption of Murine Organic Anion-Transporting Polypeptide
1b2 (oatp1b2/Slco1b2) Significantly Alters Disposition of Prototypical
Drug Substrates Pravastatin and Rifampin},
journal = {Mol. Pharmacol.},
year = {2008},
volume = {74},
pages = {320--329},
number = {2},
month = aug,
abstract = {Organic anion-transporting polypeptides (OATP) 1B1 and 1B3 are widely
acknowledged as important and rate-limiting to the hepatic uptake
of many drugs in clinical use. Accordingly, to better understand
the in vivo relevance of OATP1B transporters, targeted disruption
of murine Slco1b2 gene was carried out. It is noteworthy that Slco1b2(-/-)
mice were fertile, developed normally, and exhibited no overt phenotypic
abnormalities. We confirmed the loss of Oatp1b2 expression in liver
using real-time polymerase chain reaction, Western Blot analysis,
and immunohistochemistry. Expression of Oatp1a4 and Oatp2b1 but not
Oatp1a1 was greater in female Slco1b2(-/-) mice, but expression of
other non-OATP transporters did not significantly differ between
wild-type and Slco1b2(-/-) male mice. Total bilirubin level was elevated
by 2-fold in the Slco1b2(-/-) mice despite the fact that liver enzymes
ALT and AST were normal. Pharmacological characterization was carried
out using two prototypical substrates of human OATP1B1 and -1B3,
rifampin and pravastatin. After a single intravenous dose of rifampin
(1 mg/kg), a 1.7-fold increase in plasma area under the concentration-time
curve (AUC) was observed, whereas the liver-to-plasma ratio was reduced
by 5-fold, and nearly 8-fold when assessed at steady-state conditions
after 24 h of continuous subcutaneous infusion in Slco1b2(-/-) mice.
Likewise, continuous subcutaneous infusion at low (8 {micro}g/h)
or high (32 {micro}g/h) dose rates of pravastatin resulted in a 4-fold
lower liver-plasma ratio in the in Slco1b2(-/-) mice. This is the
first report of altered drug disposition profile in the Slco1b2 knockout
mice and suggests the utility of this model for understanding the
in vivo role of hepatic OATP transporters in drug disposition.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/74/2/320}
}
@ARTICLE{Zahn2010,
author = {Zahn, Laura and Ma, Xuan and Altman, Naomi and Zhang, Qing and Wall,
P Kerr and Tian, Donglan and Gibas, Cynthia and Gharaibeh, Raad and
Leebens-Mack, James and dePamphilis, Claude and Ma, Hong},
title = {Comparative transcriptomics among floral organs of the basal eudicot
Eschscholzia californica as reference for floral evolutionary developmental
studies},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R101},
number = {10},
abstract = {BACKGROUND:Molecular genetic studies of floral development have concentrated
in several core eudicots and grasses (monocots), which have canalized
floral forms. Basal eudicots possess a wider range of floral morphologies
than the core eudicots and grasses and can serve as an evolutionary
link between core eudicots and monocots, and provide a reference
for studies of other basal angiosperms. Recent advances in genomics
have enabled researchers to profile gene activities during floral
development, primarily in the eudicot Arabidopsis thaliana and the
monocots rice and maize. However, our understanding of floral developmental
processes among the basal eudicots remains limited. RESULTS:Using
a recently generated EST (expressed sequence tag) set, we have designed
an oligonucleotide microarray for the basal eudicot Eschscholzia
californica (California poppy). We performed microarray experiments
with an interwoven-loop design in order to characterize the E. californica
floral transcriptome and to identify differentially expressed genes
in flower buds with pre-meiotic and meiotic cells, four floral organs
at pre-anthesis stages (sepals, petals, stamens and carpels), developing
fruits, and leaves. CONCLUSION:Our results provide a foundation for
comparative gene expression studies between eudicots and basal angiosperms.
We identified whorl-specific gene expression patterns in E. californica
and examined the floral expression of several gene families. Interestingly,
most E. californica homologs of Arabidopsis genes important for flower
development, except for genes encoding MADS-box transcription factors,
show different expression patterns between the two species. Our comparative
transcriptomics study highlights the unique evolutionary position
of E. californica compared with basal angiosperms and core eudicots.},
doi = {10.1186/gb-2010-11-10-r101},
issn = {1465-6906},
pubmedid = {20950453},
url = {http://genomebiology.com/2010/11/10/R101}
}
@ARTICLE{Zaidi2011,
author = {Zaidi, M. Raza and Davis, Sean and Noonan, Frances P. and Graff-Cherry,
Cari and Hawley, Teresa S. and Walker, Robert L. and Feigenbaum,
Lionel and Fuchs, Elaine and Lyakh, Lyudmila and Young, Howard A.
and Hornyak, Thomas J. and Arnheiter, Heinz and Trinchieri, Giorgio
and Meltzer, Paul S. and De Fabo, Edward C. and Merlino, Glenn},
title = {Interferon-[ggr] links ultraviolet radiation to melanomagenesis in
mice},
journal = {Nature},
year = {2011},
volume = {469},
pages = {548--553},
number = {7331},
month = jan,
comment = {10.1038/nature09666},
issn = {0028-0836},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited.
All Rights Reserved.},
url = {http://dx.doi.org/10.1038/nature09666}
}
@ARTICLE{Zajac2010,
author = {Zajac, Magdalena and Gomez, Gonzalo and Benitez, Javier and Martínez-Delgado,
Beatriz},
title = {Molecular signature of response and potential pathways related to
resistance to the HSP90 inhibitor, 17AAG, in breast cancer},
journal = {BMC Medical Genomics},
year = {2010},
volume = {3},
pages = {44},
number = {1},
abstract = {BACKGROUND:HSP90 may be a favorable target for investigational therapy
in breast cancer. In fact, the HSP90 inhibitor, 17AAG, currently
has entered in phase II clinical trials as an anticancer agent in
breast and other tumors. Since HSP90 inhibition leads to global depletion
of oncogenic proteins involved in multiple pathways we applied global
analysis using gene array technology to study new genes and pathways
involved in the drug response in breast cancer.METHODS:Gene expression
profiling using Whole Human Genome Agilent array technology was applied
to a total of six sensitive and two resistant breast cancer cell
lines pre-treatment and treated with the 17AAG for 24 and 48 hours.RESULTS:We
have identified a common molecular signature of response to 17AAG
composed of 35 genes which include novel pharmacodynamic markers
of this drug. In addition, different patterns of HSP90 client transcriptional
changes after 17AAG were identified associated to the sensitive cell
lines, which could be useful to evaluate drug effectiveness. Finally,
we have found differentially expressed pathways associated to resistance
to 17AAG. We observed significant activation of NF-?B and MAPK pathways
in resistant cells upon treatment, indicating that these pathways
could be potentially targeted to overcome resistance.CONCLUSIONS:Our
study shows that global mRNA expression analysis is a useful strategy
to examine molecular effects of drugs, which allowed us the discovery
of new biomarkers of 17AAG activity and provided more insights into
the complex mechanism of 17AAG resistance.},
doi = {10.1186/1755-8794-3-44},
issn = {1755-8794},
pubmedid = {20920318},
url = {http://www.biomedcentral.com/1755-8794/3/44}
}
@ARTICLE{Zajac2008,
author = {Zajac, Pawel and Pettersson, Erik and Gry, Marcus and Lundeberg,
Joakim and Ahmadian, Afshin},
title = {Expression profiling of signature gene sets with trinucleotide threading},
journal = {Genomics},
year = {2008},
volume = {91},
pages = {209--217},
number = {2},
month = feb,
abstract = {In recent years, studies have shown that expression profiling of carefully
chosen intermediary gene sets, comprising approximately 10 to 100
genes, can convey the most relevant information compared to much
more complex whole-genome studies. In this paper, we present a novel
method suitable for expression profiling of moderate gene sets in
a large number of samples. The assay implements the parallel amplification
features of the trinucleotide threading technique (TnT), which encompasses
linear transcript-based DNA thread formation in conjunction with
exponential multiplexed thread amplification. The amplifications
bestow the method with high sensitivity. The TnT procedure together
with thread detection, relying on thread-specific primer extension
followed by hybridization to universal tag arrays, allows for three
distinction levels, thus offering high specificity. Additionally,
the assay is easily automated and flexible. A gene set, comprising
18 protein epitope signature tags from the Swedish Human Protein
Atlas program, was analyzed with the TnT-based approach and the data
were compared with those generated by both real-time PCR and genome-wide
cDNA arrays, with the highest correlation observed between TnT and
real-time PCR. Taken together, expression profiling with trinucleotide
threading represents a reliable approach for studies of intermediary
gene sets.},
issn = {0888-7543},
keywords = {TnT, Gene expression profiling, Multiplex, Real-time PCR, Microarray,
HPA},
url = {http://www.sciencedirect.com/science/article/B6WG1-4R8M0CV-1/2/5326035aff4ed78b3d0d44db5ff92431}
}
@ARTICLE{Zak2011,
author = {Zak, Daniel E. and Zak, Daniel E. and Schmitz, Frank and Schmitz,
Frank and Gold, Elizabeth S. and Gold, Elizabeth S. and Diercks,
Alan H. and Diercks, Alan H. and Peschon, Jacques J. and Peschon,
Jacques J. and Valvo, Joe S. and Valvo, Joe S. and Niemisto, Antti
and Niemisto, Antti and Podolsky, Irina and Podolsky, Irina and Fallen,
Shannon G. and Fallen, Shannon G. and Suen, Rosa and Suen, Rosa and
Stolyar, Tetyana and Stolyar, Tetyana and Johnson, Carrie D. and
Johnson, Carrie D. and Kennedy, Kathleen A. and Kennedy, Kathleen
A. and Hamilton, M. Kristina and Hamilton, M. Kristina and Siggs,
Owen M. and Siggs, Owen M. and Beutler, Bruce and Beutler, Bruce
and Aderem, Alan and Aderem, Alan},
title = {Systems analysis identifies an essential role for SHANK-associated
RH domain-interacting protein (SHARPIN) in macrophage Toll-like receptor
2 (TLR2) responses},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {11536-11541},
number = {28},
abstract = {Precise control of the innate immune response is essential to ensure
host defense against infection while avoiding inflammatory disease.
Systems-level analyses of Toll-like receptor (TLR)-stimulated macrophages
suggested that SHANK-associated RH domain-interacting protein (SHARPIN)
might play a role in the TLR pathway. This hypothesis was supported
by the observation that macrophages derived from chronic proliferative
dermatitis mutation (cpdm) mice, which harbor a spontaneous null
mutation in the Sharpin gene, exhibited impaired IL-12 production
in response to TLR activation. Systems biology approaches were used
to define the SHARPIN-regulated networks. Promoter analysis identified
NF-{kappa}B and AP-1 as candidate transcription factors downstream
of SHARPIN, and network analysis suggested selective attenuation
of these pathways. We found that the effects of SHARPIN deficiency
on the TLR2-induced transcriptome were strikingly correlated with
the effects of the recently described hypomorphic L153P/panr2 point
mutation in Ikbkg [NF-{kappa}B Essential Modulator (NEMO)], suggesting
that SHARPIN and NEMO interact. We confirmed this interaction by
co-immunoprecipitation analysis and furthermore found it to be abrogated
by panr2. NEMO-dependent signaling was affected by SHARPIN deficiency
in a manner similar to the panr2 mutation, including impaired p105
and ERK phosphorylation and p65 nuclear localization. Interestingly,
SHARPIN deficiency had no effect on I{kappa}B degradation and on
p38 and JNK phosphorylation. Taken together, these results demonstrate
that SHARPIN is an essential adaptor downstream of the branch point
defined by the panr2 mutation in NEMO.},
doi = {10.1073/pnas.1107577108},
eprint = {http://www.pnas.org/cgi/reprint/108/28/11536.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/28/11536}
}
@ARTICLE{Zakhrabekova2007,
author = {Zakhrabekova, Shakhira and Gough, Simon P. and Lundqvist, Udda and
Hansson, Mats},
title = {Comparing two microarray platforms for identifying mutated genes
in barley (Hordeum vulgare L.)},
journal = {Plant Physiology and Biochemistry},
year = {2007},
volume = {45},
pages = {617--622},
number = {8},
month = aug,
abstract = {We have previously described the evaluation of a cDNA microarray platform
to identify and clone mutated barley (Hordeum vulgare L.) genes,
using their transcriptionally defective mutant alleles (S. Zakhrabekova,
C.G. Kannangara, D. von Wettstein, M. Hansson, A microarray approach
for identification of mutated genes, Plant Physiol. Biochem. 40 (2002)
189-197). It was concluded that competitive hybridization between
phenotypically similar mutants could specifically highlight an arrayed
clone, corresponding to the mutated gene. In this study we evaluate
whether the Affymetrix microarray platform can be used for the same
purpose. The Affymetrix barley microarray contains a large number
of clones (22,792 probe sets). In this and the previous study we
used two barley mutant strains, xantha-h.57 and xantha-f.27, with
known mutations in different subunit genes of the chlorophyll biosynthetic
enzyme magnesium chelatase (EC 6.6.1.1). Mutant xantha-h.57 produces
no Xantha-h mRNA whereas in xantha-f.27 the nonsense mutation in
the last exon of the gene, results in nonsense-mediated decay of
Xantha-f mRNA. We conclude that the Affymetrix platform meets our
requirements and that our approach successfully highlighted the arrayed
Xantha-h clone and that Xantha-f was among the top fourteen candidates.},
issn = {0981-9428},
keywords = {Barley, Cloning, Hordeum vulgare, Magnesium chelatase, Microarray,
Mutant, Xantha},
url = {http://www.sciencedirect.com/science/article/B6VRD-4NVT9SK-1/2/52e7e4df6171363a1fa7491182e21433}
}
@ARTICLE{Zakrzewska2005,
author = {Zakrzewska, Anna and Boorsma, Andre and Brul, Stanley and Hellingwerf,
Klaas J. and Klis, Frans M.},
title = {Transcriptional Response of Saccharomyces cerevisiae to the Plasma
Membrane-Perturbing Compound Chitosan},
journal = {Eukaryot. Cell},
year = {2005},
volume = {4},
pages = {703--715},
number = {4},
month = apr,
abstract = {Chitosan is a plasma membrane-perturbing compound consisting of linear
chains of {beta}-1,4-linked glucosamine residues, which at acidic
pHs become positively charged. It is extensively used as an antimicrobial
compound, yet its mode of action is still unresolved. Chitosan strongly
affected the growth of the yeast Saccharomyces cerevisiae, the food
spoilage yeast Zygosaccharomyces bailii, and two human-pathogenic
yeasts, Candida albicans and Candida glabrata. Microarray analysis
of yeast cells treated with sublethal concentrations of chitosan
revealed induction of the environmental stress response and three
more major transcriptional responses. The first was a rapid and stable
Cin5p-mediated response. Cin5p/Yap4p is a transcription factor involved
in various stress responses. Deletion of CIN5 led to increased chitosan
sensitivity. The second was a Crz1p-mediated response, which is delayed
compared to the Cin5p response. Crz1p is a transcription factor of
the calcineurin pathway. Cells deleted for CRZ1 or treated with the
calcineurin inhibitor FK506 became hypersensitive to chitosan, supporting
the notion that the Crz1p-controlled response offers protection against
chitosan. The third was a strong Rlm1p-mediated response which ran
parallel in time with the Crz1p-regulated response. Rlm1p is a transcription
factor of the cell wall integrity pathway, which is activated by
cell wall stress. Importantly, chitosan-treated cells became more
resistant to {beta}-1,3-glucanase, which is a well-known response
to cell wall stress. We propose that the transcriptional response
to chitosan may be representative of other plasma membrane-perturbing
compounds.},
url = {http://ec.asm.org/cgi/content/abstract/4/4/703}
}
@ARTICLE{Zamagni2009,
author = {Zamagni, Claudio and Wirtz, Ralph M and De Iaco, Pierandrea and Rosati,
Marta and Veltrup, Elke and Rosati, Federica and Capizzi, Elisa and
Cacciari, Nicoletta and Alboni, Carlo and Bernardi, Alessandra and
Massari, Francesco and Quercia, Sara and D'Errico Grigioni, Antonietta
and Dietel, Manfred and Sehouli, Jalid and Denkert, Carsten and Martoni,
Andrea Angelo},
title = {Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer
patients treated with neo-adjuvant chemotherapy: determination by
array and kinetic PCR in fresh tissue biopsies},
journal = {Endocr. Relat. Cancer},
year = {2009},
volume = {16},
pages = {1241--1249},
number = {4},
month = dec,
abstract = {Oestrogen receptors (ESRs) regulate the growth and differentiation
of normal ovarian epithelia. However, to date their role as biomarkers
in the clinical setting of ovarian cancer remains unclear. In view
of potential endocrine treatment options, we tested the role of ESR1
mRNA expression in ovarian cancer in the context of a neo-adjuvant
chemotherapy trial. Study participants had epithelial ovarian or
peritoneal carcinoma unsuitable for optimal upfront surgery and were
treated with neo-adjuvant platinum-based chemotherapy before surgery.
RNA was isolated from frozen tumour biopsies before treatment. RNA
expression of ESR1 was determined by microarray and reverse transcriptase
kinetic PCR technologies. The prognostic value of ESR1 was tested
using univariate and multivariate Cox proportional hazards models,
Kaplan-Meier survival statistics and the log-rank test. ESR1 positively
correlates with proliferation markers and histopathological grading.
ESR1 was a significant predictor of survival as a continuous variable
in the univariate Cox regression analysis. In multivariate analysis,
elevated baseline ESR1 mRNA levels predicted prolonged progression-free
survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant
chemotherapy, independently of pathological grade and age. We conclude
that pretreatment ESR1 mRNA is associated with tumour growth and
is a strong prognostic factor in ovarian cancer, independent of the
strongest clinical parameters used in clinical routine. We suggest
that ESR1 mRNA status should be considered in order to minimize possible
confounding effects in ovarian cancer clinical trials, and that early
treatment with anti-hormonal agents based on reliable hormone receptor
status determination is worth investigating.},
url = {http://erc.endocrinology-journals.org/cgi/content/abstract/16/4/1241}
}
@ARTICLE{Zamah2010,
author = {Zamah, A.M. and Hsieh, M. and Chen, J. and Vigne, J.L. and Rosen,
M.P. and Cedars, M.I. and Conti, M.},
title = {Human oocyte maturation is dependent on LH-stimulated accumulation
of the epidermal growth factor-like growth factor, amphiregulin},
journal = {Hum. Reprod.},
year = {2010},
volume = {25},
pages = {2569--2578},
number = {10},
month = oct,
abstract = {BACKGROUNDThe LH surge promotes ovulation via activation of multiple
signaling networks in the ovarian follicle. Studies in animal models
have shown the importance of LH-induced activation of the epidermal
growth factor (EGF)signaling network in critical peri-ovulatory events.
We investigated the biological significance of regulatory mechanisms
mediated by EGF-like growth factors during LH stimulation in humans.
METHODSWe characterized the EGF signaling network in mature human
ovarian follicles using in vivo and in vitro approaches. Amphiregulin
(AREG) levels were measured in 119 follicular fluid (FF) samples
from IVF/ICSI patients. Biological activity of human FF was assessed
using in vitro oocyte maturation, cumulus expansion and cell mitogenic
assays. RESULTSAREG is the most abundant EGF-like growth factor accumulating
in the FF of mature follicles of hCG-stimulated patients. No AREG
was detected before the LH surge or before hCG stimulation of granulosa
cells in vitro, demonstrating that the accumulation of AREG requires
gonadotrophin stimulation. Epiregulin and betacellulin mRNA were
detected in both human mural and cumulus granulosa cells, although
at significantly lower levels than AREG. FF from stimulated follicles
causes cumulus expansion and oocyte maturation in a reconstitution
assay. Immunodepletion of AREG abolishes the ability of FF to stimulate
expansion (P < 0.0001) and oocyte maturation (P < 0.05), confirming
the biological activity of AREG. Conversely, mitogenic activity of
FF remained after depletion of AREG, indicating that other mitogens
accumulate in FF. FF from follicles yielding an immature germinal
vesicle oocyte or from an oocyte that develops into an aberrant embryo
contains lower AREG levels than that from follicles yielding a healthy
oocyte (P = 0.008). CONCLUSIONSEGF-like growth factors play a role
in critical peri-ovulatory events in humans, and AREG accumulation
is a useful marker of gonadotrophin stimulation and oocyte competence.},
url = {http://humrep.oxfordjournals.org/cgi/content/abstract/25/10/2569}
}
@ARTICLE{Zaman2010,
author = {Zaman, Gul and Saxon, Leanne K. and Sunters, Andrew and Hilton, Helen
and Underhill, Peter and Williams, Debbie and Price, Joanna S. and
Lanyon, Lance E.},
title = {Loading-related regulation of gene expression in bone in the contexts
of estrogen deficiency, lack of estrogen receptor [alpha] and disuse},
journal = {Bone},
year = {2010},
volume = {46},
pages = {628--642},
number = {3},
month = mar,
abstract = {Loading-related changes in gene expression in resident cells in the
tibia of female mice in the contexts of normality (WT), estrogen
deficiency (WT-OVX), absence of estrogen receptor [alpha] (ER[alpha]-/-)
and disuse due to sciatic neurectomy (WT-SN) were established by
microarray. Total RNA was extracted from loaded and contra-lateral
non-loaded tibiae at selected time points after a single, short period
of dynamic loading sufficient to engender an osteogenic response.
There were marked changes in the expression of many genes according
to context as well as in response to loading within those contexts.
In WT mice at 3, 8, 12 and 24 h after loading the expression of 642,
341, 171 and 24 genes, respectively, were differentially regulated
compared with contra-lateral bones which were not loaded. Only a
few of the genes differentially regulated by loading in the tibiae
of WT mice have recognized roles in bone metabolism or have been
linked previously to osteogenesis (Opn, Sost, Esr1, Tgfb1, Lrp1,
Ostn, Timp, Mmp, Ctgf, Postn and Irs1, BMP and DLX5). The canonical
pathways showing the greatest loading-related regulation were those
involving pyruvate metabolism, mitochondrial dysfunction, calcium-induced
apoptosis, glycolysis/gluconeogenesis, aryl hydrocarbon receptor
and oxidative phosphorylation. In the tibiae from WT-OVX, ER[alpha]-/-
and WT-SN mice, 440, 439 and 987 genes respectively were differentially
regulated by context alone compared to WT. The early response to
loading in tibiae of WT-OVX mice involved differential regulation
compared to their contra-lateral non-loaded pair of fewer genes than
in WT, more down-regulation than up-regulation and a later response.
This was shared by WT-SN. In tibiae of ER[alpha]-/- mice, the number
of genes differentially regulated by loading was markedly reduced
at all time points. These data indicate that in resident bone cells,
both basal and loading-related gene expression is substantially modified
by context. Many of the genes differentially regulated by the earliest
loading-related response were primarily involved in energy metabolism
and were not specific to bone.},
issn = {8756-3282},
keywords = {Gene expression, Mechanical loading, Bone, Estrogen, ER[alpha]},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4XHVH3W-2/2/1e8a07a53c1198d91095e0d71d0cf969}
}
@ARTICLE{Zambelli2010,
author = {Zambelli, Diana and Zuntini, Monia and Nardi, Filippo and Manara,
Maria Cristina and Serra, Massimo and Landuzzi, Lorena and Lollini,
Pier-Luigi and Ferrari, Stefano and Alberghini, Marco and Llombart-Bosch,
Antonio and Piccolo, Enza and Iacobelli, Stefano and Picci, Piero
and Scotlandi, Katia},
title = {Biological indicators of prognosis in Ewing's sarcoma: An emerging
role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)},
journal = {Int. J. Cancer},
year = {2010},
volume = {126},
pages = {41--52},
number = {1},
abstract = {Abstract 10.1002/ijc.24670.abs Starting from an experimental model
that accounts for the 2 most important adverse processes to successful
therapy of Ewing's sarcoma (EWS), chemoresistance and the presence
of metastasis at the time of diagnosis, we defined a molecular signature
of potential prognostic value. Functional annotation of differentially
regulated genes revealed 3 major networks related to cell cycle,
cell-to-cell interactions and cellular development. The prognostic
impact of 8 genes, representative of these 3 networks, was validated
in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2,
LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death
and lower risk to develop metastasis. At multivariate analysis, LGALS3BP,
a matricellular protein with a role in tumor progression and metastasis,
was the most important predictor of event-free survival and overall
survival. The association between LGALS3BP and prognosis was confirmed
at protein level, when expression of the molecule was determined
in tumor tissues but not in serum, indicating a role for the protein
at local tumor microenvironment. Engineered enhancement of LGALS3BP
expression in EWS cells resulted in inhibition of anchorage independent
cell growth and reduction of cell migration and metastasis. Silencing
of LGALS3BP expression reverted cell behavior with respect to in
vitro parameters, thus providing further functional validation of
genetic data obtained in clinical samples. Thus, we propose LGALS3BP
as a novel reliable indicator of prognosis, and we offer genetic
signatures to the scientific communities for cross-validation and
meta-analysis, which are indispensable tools for a rare tumor such
as EWS.},
issn = {1097-0215},
keywords = {Ewing's sarcoma, lectin galactoside-binding soluble 3 binding protein,
prognostic markers, microarray analysis, metastasis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24670}
}
@ARTICLE{Zamboni2010,
author = {Zamboni, Anita and Di Carli, Mariasole and Guzzo, Flavia and Stocchero,
Matteo and Zenoni, Sara and Ferrarini, Alberto and Tononi, Paola
and Toffali, Ketti and Desiderio, Angiola and Lilley, Kathryn S.
and Pe, M. Enrico and Benvenuto, Eugenio and Delledonne, Massimo
and Pezzotti, Mario},
title = {Identification of Putative Stage-Specific Grapevine Berry Biomarkers
and Omics Data Integration into Networks},
journal = {Plant Physiology},
year = {2010},
volume = {154},
pages = {1439--1459},
number = {3},
month = nov,
abstract = {The analysis of grapevine (Vitis vinifera) berries at the transcriptomic,
proteomic, and metabolomic levels can provide great insight into
the molecular events underlying berry development and postharvest
drying (withering). However, the large and very different data sets
produced by such investigations are difficult to integrate. Here,
we report the identification of putative stage-specific biomarkers
for berry development and withering and, to our knowledge, the first
integrated systems-level study of these processes. Transcriptomic,
proteomic, and metabolomic data were integrated using two different
strategies, one hypothesis free and the other hypothesis driven.
A multistep hypothesis-free approach was applied to data from four
developmental stages and three withering intervals, with integration
achieved using a hierarchical clustering strategy based on the multivariate
bidirectional orthogonal projections to latent structures technique.
This identified stage-specific functional networks of linked transcripts,
proteins, and metabolites, providing important insights into the
key molecular processes that determine the quality characteristics
of wine. The hypothesis-driven approach was used to integrate data
from three withering intervals, starting with subdata sets of transcripts,
proteins, and metabolites. We identified transcripts and proteins
that were modulated during withering as well as specific classes
of metabolites that accumulated at the same time and used these to
select subdata sets of variables. The multivariate bidirectional
orthogonal projections to latent structures technique was then used
to integrate the subdata sets, identifying variables representing
selected molecular processes that take place specifically during
berry withering. The impact of this holistic approach on our knowledge
of grapevine berry development and withering is discussed.},
url = {http://www.plantphysiol.org/cgi/content/abstract/154/3/1439}
}
@ARTICLE{Zamboni2009,
author = {Zamboni, Anita and Gatto, Pamela and Cestaro, Alessandro and Pilati,
Stefania and Viola, Roberto and Mattivi, Fulvio and Moser, Claudio
and Velasco, Riccardo},
title = {Grapevine cell early activation of specific responses to DIMEB, a
resveratrol elicitor},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {363},
number = {1},
abstract = {BACKGROUND:In response to pathogen attack, grapevine synthesizes phytoalexins
belonging to the family of stilbenes. Grapevine cell cultures represent
a good model system for studying the basic mechanisms of plant response
to biotic and abiotic elicitors. Among these, modified ß-cyclodextrins
seem to act as true elicitors inducing strong production of the stilbene
resveratrol.RESULTS:The transcriptome changes of Vitis riparia ×
Vitis berlandieri grapevine cells in response to the modified ß-cyclodextrin,
DIMEB, were analyzed 2 and 6 h after treatment using a suppression
subtractive hybridization experiment and a microarray analysis respectively.
At both time points, we identified a specific set of induced genes
belonging to the general phenylpropanoid metabolism, including stilbenes
and hydroxycinnamates, and to defence proteins such as PR proteins
and chitinases. At 6 h we also observed a down-regulation of the
genes involved in cell division and cell-wall loosening.CONCLUSIONS:We
report the first large-scale study of the molecular effects of DIMEB,
a resveratrol inducer, on grapevine cell cultures. This molecule
seems to mimic a defence elicitor which enhances the physical barriers
of the cell, stops cell division and induces phytoalexin synthesis.},
doi = {10.1186/1471-2164-10-363},
issn = {1471-2164},
pubmedid = {19660119},
url = {http://www.biomedcentral.com/1471-2164/10/363}
}
@ARTICLE{Zambrano2011,
author = {Zambrano, Jose and Ettayebi, Khalil and Maaty, Walid and Faunce,
Nicholas and Bothner, Brian and Hardy, Michele},
title = {Rotavirus infection activates the UPR but modulates its activity},
journal = {Virology Journal},
year = {2011},
volume = {8},
pages = {359},
number = {1},
abstract = {BACKGROUND:Rotaviruses are known to modulate the innate antiviral
defense response driven by IFN. The purpose of this study was to
identify changes in the cellular proteome in response to rotavirus
infection in the context of the IFN response. We also sought to identify
proteins outside the IFN induction and signaling pathway that were
modulated by rotavirus infection.METHODS:2D-DIGE and image analysis
were used to identify cellular proteins that changed in levels of
expression in response to rotavirus infection, IFN treatment, or
IFN treatment prior to infection. Immunofluorescence microscopy was
used to determine the subcellular localization of proteins associated
with the unfolded protein response (UPR).RESULTS:The data show changes
in the levels of multiple proteins associated with cellular stress
in infected cells, including levels of ER chaperones GRP78 and GRP94.
Further investigations showed that GRP78, GRP94 and other proteins
with roles in the ER-initiated UPR including PERK, CHOP and GADD34,
were localized to viroplasms in infected cells.CONCLUSIONS:Together
the results suggest rotavirus infection activates the UPR, but modulates
its effects by sequestering sensor, transcription factor, and effector
proteins in viroplasms. The data consequently also suggest that viroplasms
may directly or indirectly play a fundamental role in regulating
signaling pathways associated with cellular defense responses.},
doi = {10.1186/1743-422X-8-359},
issn = {1743-422X},
pubmedid = {21774819},
url = {http://www.virologyj.com/content/8/1/359}
}
@ARTICLE{Zammarchi2011,
author = {Zammarchi, Francesca and de Stanchina, Elisa and Bournazou, Eirini
and Supakorndej, Teerawit and Martires, Kathryn and Riedel, Elyn
and Corben, Adriana D. and Bromberg, Jacqueline F. and Cartegni,
Luca},
title = {Antitumorigenic potential of STAT3 alternative splicing modulation},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {17779-17784},
number = {43},
abstract = {Signal transducer and activator of transcription 3 (STAT3) plays a
central role in the activation of multiple oncogenic pathways. Splicing
variant STAT3{beta} uses an alternative acceptor site within exon
23 that leads to a truncated isoform lacking the C-terminal transactivation
domain. Depending on the context, STAT3{beta} can act as a dominant-negative
regulator of transcription and promote apoptosis. We show that modified
antisense oligonucleotides targeted to a splicing enhancer that regulates
STAT3 exon 23 alternative splicing specifically promote a shift of
expression from STAT3 to STAT3{beta}. Induction of endogenous STAT3{beta}
leads to apoptosis and cell-cycle arrest in cell lines with persistent
STAT3 tyrosine phosphorylation compared with total STAT3 knockdown
obtained by forced splicing-dependent nonsense-mediated decay (FSD-NMD).
Comparison of the molecular effects of splicing redirection to STAT3
knockdown reveals a unique STAT3{beta} signature, with a down-regulation
of specific targets (including lens epithelium-derived growth factor,
p300/CBP-associated factor, CyclinC, peroxisomal biogenesis factor
1, and STAT1{beta}) distinct from canonical STAT3 targets typically
associated with total STAT3 knockdown. Furthermore, similar in vivo
redirection of STAT3 alternative splicing leads to tumor regression
in a xenograft cancer model, demonstrating how pharmacological manipulation
of a single key splicing event can manifest powerful antitumorigenic
properties and validating endogenous splicing reprogramming as an
effective cancer therapeutic approach.},
doi = {10.1073/pnas.1108482108},
eprint = {http://www.pnas.org/cgi/reprint/108/43/17779.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/43/17779}
}
@ARTICLE{Zamo2007,
author = {Zamo, Alberto and Bertolaso, Anna and Franceschetti, Ilaria and Weirich,
Gregor and Capelli, Paola and Pecori, Sara and Chilosi, Marco and
Hoefler, Heinz and Menestrina, Fabio and Scarpa, Aldo},
title = {Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT
and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors:
Diagnostic Applications and Report of a New KIT Mutation},
journal = {J. Mol. Diagn.},
year = {2007},
volume = {9},
pages = {151--157},
number = {2},
month = apr,
abstract = {Gastrointestinal stromal tumors (GISTs) frequently harbor mutations
in the KIT and PDGFRA genes, the presence and type of which correlate
with the response to the kinase inhibitor imatinib mesylate. Because
most GIST mutations are deletions/insertions, we used a microfluidic
apparatus to detect these size variations in polymerase chain reaction-amplified
DNA. This approach, termed microfluidic deletion/insertion analysis
(MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded
CD117-positive GISTs (60%), comprising 25 deletions and five insertions.
Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions,
including two 3-bp alterations. Sequencing of all 20 MIDIA-negative
samples also showed highly consistent results with MIDIA because
10 cases were wild type and eight displayed a single base substitution
in which detection by MIDIA was not expected. Sequencing also revealed
a 3-bp deletion undetected by MIDIA, thus establishing the resolution
limit of MIDIA at deletions/insertions [≥]3 bp. Denaturing high-pressure
liquid chromatography analysis confirmed all mutations detected by
MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational
screening of GIST because it allowed the detection of 75% of mutated
cases (94% of deletions/insertions) in less than 30 minutes after
polymerase chain reaction amplification and at a lower cost compared
with denaturing high-pressure liquid chromatography and sequencing,
which might then be used only for MIDIA-negative cases.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/9/2/151}
}
@ARTICLE{Zamo2012,
author = {Zamo, Alberto and Bertolaso, Anna and van Raaij, Annemiek W.M. and
Mancini, Francesca and Scardoni, Maria and Montresor, Marina and
Menestrina, Fabio and van Krieken, Johan H.J.M. and Chilosi, Marco
and Groenen, Patricia J.T.A. and Scarpa, Aldo},
title = {Application of Microfluidic Technology to the BIOMED-2 Protocol for
Detection of B-Cell Clonality},
journal = {J Mol Diagn},
year = {2012},
volume = {14},
pages = {30--37},
number = {1},
month = jan,
abstract = {The BIOMED-2 protocol is widely used for detecting clonality in lymphoproliferative
disorders. The protocol requires multiple PCR reactions, which are
analyzed by either capillary electrophoresis (GeneScan analysis)
or heteroduplex PAGE analysis. We tested a microfluidic chip-based
electrophoresis device (Agilent 2100 Bioanalyzer) for the analysis
of B-cell clonality using PCR for the three framework subregions
(FR) of the Ig heavy chain gene (IGH) and PCR for two rearrangements
occurring in the Ig κ chain gene (IGK-VJ and IGK-DE). We analyzed
62 B-cell lymphomas (33 follicular and 29 nonfollicular) and 16 reactive
lymph nodes. Chip-based electrophoresis was conclusive for monoclonality
in 59/62 samples; for 20 samples, it was compared with GeneScan analysis.
Concordant results were obtained in 45/55 IGH (FR1, FR2, and FR3)
gene rearrangements, and in 34/37 IGK gene rearrangements. However,
when the chip device was used to analyze selected IGK gene rearrangements
(biallelic IGK rearrangements or IGK rearrangements in a polyclonal
background), its performance was not completely accurate. We conclude,
therefore, that this microfluidic chip-based electrophoresis device
is reliable for testing cases with dominant PCR products but is less
sensitive than GeneScan in detecting clonal peaks in a polyclonal
background for IGH PCR, or with complex IGK rearrangement patterns.},
issn = {1525-1578},
publisher = {American Society for Investigative Pathology and the Association
for Molecular Pathology,},
refid = {S1525-1578(11)00258-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1525157811002583?showall=true}
}
@ARTICLE{Zamparini2006,
author = {Zamparini, Andrea L. and Watts, Tim and Gardner, Clare E. and Tomlinson,
Simon R. and Johnston, Geoffrey I. and Brickman, Joshua M.},
title = {Hex acts with {beta}-catenin to regulate anteroposterior patterning
via a Groucho-related co-repressor and Nodal},
journal = {Development},
year = {2006},
volume = {133},
pages = {3709--3722},
number = {18},
month = sep,
abstract = {In Xenopus, the establishment of the anteroposterior axis involves
two key signalling pathways, canonical Wnt and Nodal-related TGF{beta}.
There are also a number of transcription factors that feedback upon
these pathways. The homeodomain protein Hex, an early marker of anterior
positional information, acts as a transcriptional repressor, suppressing
induction and propagation of the Spemman organiser while specifying
anterior identity. We show that Hex promotes anterior identity by
amplifying the activity of canonical Wnt signalling. Hex exerts this
activity by inhibiting the expression of Tle4, a member of the Groucho
family of transcriptional co-repressors that we identified as a Hex
target in embryonic stem (ES) cells and Xenopus embryos. This Hex-mediated
enhancement of Wnt signalling results in the upregulation of the
Nieuwkoop centre genes Siamois and Xnr3, and the subsequent increased
expression of the anterior endodermal marker Cerberus and other mesendodermal
genes downstream of Wnt signalling. We also identified Nodal as a
Hex target in ES cells. We demonstrate that in Xenopus, the Nodal-related
genes Xnr1 and Xnr2, but not Xnr5 and Xnr6, are regulated directly
by Hex. The identification of Nodal-related genes as Hex targets
explains the ability of Hex to suppress induction and propagation
of the organiser. Together, these results support a model in which
Hex acts early in development to reinforce a Wnt-mediated, Nieuwkoop-like
signal to induce anterior endoderm, and later in this tissue to block
further propagation of Nodal-related signals. The ability of Hex
to regulate the same targets in both Xenopus and mouse implies this
model is conserved.},
url = {http://dev.biologists.org/cgi/content/abstract/133/18/3709}
}
@ARTICLE{Zanation2004,
author = {Zanation, Adam M. and Yin, Xiaoying and Shores, Carol and Yarbrough,
Wendell G.},
title = {Phenotypic and microarray gene expression analysis of tri-dimensional
raft-modeled human head and neck squamous cell carcinoma},
journal = {Otolaryngology - Head and Neck Surgery},
year = {2004},
volume = {131},
pages = {577--584},
number = {5},
month = nov,
abstract = {Objectives To describe the phenotypic and gene expression differences
in monolayer and tri-dimensional cultures systems.Methods Normal
oral epithelial cells (NOEC), primary head and neck squamous cell
carcinoma (HNSCC), and HNSCC cell lines were used to create and study
modeled tri-dimensional tissue. Using cDNA microarray analysis, monolayer
and raft-modeled tri-dimensional HNSCC cell lines were compared.Results
NOEC, HNSCC, and both together can be modeled with tri-dimensional
differentiation and cytokeratin characteristics analogous to in vivo
tissue. Modeling of primary HNSCC resulted in a morphology of invasive
HNSCC with areas of direct collagen invasion and MMP2 expression.
Gene array analysis suggests that the individual cell lines themselves
are the primary gene expression predictor and not the presence of
tri-dimensional tissue architecture.Conclusions This tissue culture
modeling system approximates the differentiation and tri-dimensional
structure of in vivo tissues, and that raft modeled tri-dimensional
HNSCC does not have a significantly different gene expression profile
than the corresponding monolayer culture.},
issn = {0194-5998},
url = {http://www.sciencedirect.com/science/article/B6WP4-4DNHC6S-C/2/67190b5e4c4b6e34d46614066a5c4540}
}
@ARTICLE{Zanazzi2007,
author = {Zanazzi, Claudia and Hersmus, Remko and Veltman, Imke M. and Gillis,
Ad J.M. and van Drunen, Ellen and Beverloo, H. Berna and Hegmans,
Joost P.J.J. and Verweij, Marielle and Lambrecht, Bart N. and Oosterhuis,
J. Wolter and Looijenga, Leendert H.J.},
title = {Gene expression profiling and gene copy-number changes in malignant
mesothelioma cell lines},
journal = {Genes Chromosom. Cancer},
year = {2007},
volume = {46},
pages = {895--908},
number = {10},
abstract = {Abstract 10.1002/gcc.20475.abs Malignant mesothelioma (MM) is an asbestos-induced
tumor that acquires aneuploid DNA content during the tumorigenic
process. We used instable MM cell lines as an in vitro model to study
the impact of DNA copy-number changes on gene expression profiling,
in the course of their chromosomal redistribution process. Two MM
cell lines, PMR-MM2 (early passages of in vitro culture) and PMR-MM7
(both early and late passages of in vitro culture), were cytogenetically
characterized. Genomic gains and losses were precisely defined using
microarray-based comparative genomic hybridization (array-CGH), and
minimal overlapping analysis led to the identification of the common
unbalanced genomic regions. Using the U133Plus 2.0 Affymetrix gene
chip array, we analyzed PMR-MM7 early and late passages for genome-wide
gene expression, and correlated the differentially expressed genes
with copy-number changes. The presence of a high number of genetic
imbalances occurring from early to late culture steps reflected the
tendency of MM cells toward genomic instability. The selection of
specific chromosomal abnormalities observed during subsequent cultures
demonstrated the spontaneous evolution of the cancer cells in an
in vitro environment. MM cell lines were characterized by copy-number
changes associated with the TP53 apoptotic pathway already present
at the first steps of in vitro culture. Prolonged culture led to
acquisition of additional chromosomal copy-number changes associated
with dysregulation of genes involved in cell adhesion, regulation
of mitotic cell cycle, signal transduction, carbohydrate metabolism,
motor activity, glycosaminoglycan biosynthesis, protein binding activity,
lipid transport, ATP synthesis, and methyltransferase activity. ©
2007 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20475}
}
@ARTICLE{Zande2010,
author = {van der Zande, Meike and Walboomers, X. Frank and Brännvall, Mathias
and Olalde, Beatriz and Jurado, Maria J. and �lava, J. Iñaki and
Jansen, John A.},
title = {Genetic profiling of osteoblast-like cells cultured on a novel bone
reconstructive material, consisting of poly-l-lactide, carbon nanotubes
and microhydroxyapatite, in the presence of bone morphogenetic protein-2},
journal = {Acta Biomater},
year = {2010},
volume = {6},
pages = {4352--4360},
number = {11},
month = nov,
abstract = {In bone tissue engineering composite materials have been introduced,
combining a degradable polymer matrix with, for instance, carbon
nanotubes (CNTs) to improve mechanical properties or with microhydroxyapatite
(μHA) to improve osteoconduction. The addition of bone morphogenetic
protein-2 (BMP-2) can further improve the biological response to
the material. However, the influence of such an elaborate composite
formation on osteoprogenitor cells is unknown. To examine this, rat
bone marrow (RBM) cells were cultured on porous poly-l-lactic acid
and composite scaffolds, with or without added BMP-2. Cell proliferation
and differentiation were studied using DNA, alkaline phosphatase
and scanning electron microscopic analysis. Further, genetic profiles
were examined by microarray investigation. Results showed that the
composite scaffold had no significant effect on the proliferation
of RBM cells, but indicated a negative effect on cell differentiation.
The addition of BMP-2 also had no significant effect on the proliferation
of RBM cells, but differentiation towards the osteogenic lineage
was confirmed. In the arrays results, the addition of BMP-2 alone
led to the expression of genes involved in (minor) inflammation.
The composite scaffold, and even more distinctly the combination
of the composite scaffold with BMP-2, led to the expression of genes,
based on gene ontology, connected to tumorigenesis. Therefore, CNT-
and μHA-containing composite materials are not recommended as a
bone restorative material.},
issn = {1742-7061},
keywords = {In vitro, Genetic profiling, Carbon nanotubes, Hydroxyapatite, Bone
morphogenetic protein-2 (BMP-2)},
publisher = {Elsevier,},
refid = {S1742-7061(10)00279-5},
url = {http://linkinghub.elsevier.com/retrieve/pii/S1742706110002795?showall=true}
}
@ARTICLE{Zander2008,
author = {Zander, L. and Bemark, M.},
title = {Identification of genes deregulated during serum-free medium adaptation
of a Burkitt's lymphoma cell line},
journal = {Cell Proliferation},
year = {2008},
volume = {41},
pages = {136--155},
number = {1},
abstract = {Abstract. Objective: Serum is usually added to growth media when
mammalian cells are cultured in vitro to supply the cells with growth
factors, hormones, nutrients and trace elements. Defined proteins
and metal ions, such as insulin, growth factors, transferrin and
sodium selenite, are sometimes also included and can in some cases
substitute serum components. How adaptation to serum free media influences
cells has not been studied in detail. Materials and Methods: We have
adapted the Burkitt's lymphoma line Ramos to a serum-free medium
that supports long-term survival and studied gene expression changes
that occurred during the adaptation process. Results and Conclusions:
The adaptation process was characterized by initial cell population
growth arrest, and after that extensive cell death, followed by proliferation
and long-term survival of clonal cultures. Proliferation and cell
cycle progression of the serum-free cultures closely mimicked that
of serum-dependent cells. Affymetrix micro-array technology was used
to identify gene expression alterations that had occurred during
the adaptation. Most changes were subtle, but frequently the genes
with altered expression were involved in basal cellular functions
such as cell division, cell cycle regulation, apoptosis and cell
signalling. Some alterations were restored when the cells were transferred
back to serum-containing medium, indicating that expression of these
genes was controlled by components in serum. Others were not, and
may represent changes that were selected during the adaptation process.
Among these were, for example, several genes within the Wnt signalling
pathway.},
issn = {1365-2184},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2184.2007.00500.x}
}
@ARTICLE{Zane2010,
author = {Zane, Linda and Sibon, David and Legras, Catherine and Lachuer, Joël
and Wierinckx, Anne and Mehlen, Patrick and Delfau-Larue, Marie-Hélène
and Gessain, Antoine and Gout, Olivier and Pinatel, Christiane and
Lançon, Agnès and Mortreux, Franck and Wattel, Eric},
title = {Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but
not on c-FLIP expression},
journal = {Virology},
year = {2010},
volume = {407},
pages = {341--351},
number = {2},
month = nov,
abstract = {Here we investigate the mechanisms by which HTLV-1 infection prevents
the cell death of CD8+ T cells in vivo. We show that upon natural
infection, cloned CD8+ but not CD4+ cells from patients without malignancy
become resistant to Fas-mediated cell death and acquire an antiapoptotic
transcriptome that includes the overexpression of cIAP-2 and c-FLIP(L).
CD8+ lymphocyte-restricted cIAP-2 overexpression correlates with
resistance to Fas-mediated apoptosis and depends on tax expression
via NF-KappaB. In contrast, in the same CD8+ cells, the HTLV-1-dependent
overexpression of c-FLIP(L) does not correlate with resistance to
Fas-mediated cell death nor with tax expression. In the present model,
infected CD8+ clones are the only cell subtype in which cIAP-2 expression
correlates with resistance to cell death. These results support a
role for Tax-dependent cIAP-2 expression in preventing the death
of naturally infected CD8+ cells and thereby in their clonal expansion
in vivo.},
issn = {0042-6822},
keywords = {HTLV-1, Apoptosis, Clonal expansion, cIAP-2, c-FLIP},
url = {http://www.sciencedirect.com/science/article/B6WXR-512TFM8-1/2/d57370c15ca14ac3c8ee54933393084d}
}
@ARTICLE{Zanello2011,
author = {Zanello, Galliano and Meurens, François and Berri, Mustapha and Chevaleyre,
Claire and Melo, Sandrine and Auclair, Eric and Salmon, Henri},
title = {Saccharomyces cerevisiae decreases inflammatory responses induced
by F4+ enterotoxigenic Escherichia coli in porcine intestinal epithelial
cells},
journal = {Veterinary Immunology and Immunopathology},
year = {2011},
volume = {141},
pages = {133--138},
number = {1-2},
month = may,
abstract = {Probiotic yeasts may provide protection against intestinal inflammation
induced by enteric pathogens. In piglets, infection with F4+ enterotoxigenic
Escherichia coli (ETEC) leads to inflammation, diarrhea and intestinal
damage. In this study, we investigated whether the yeast strains
Saccharomyces cerevisiae (Sc, strain CNCM I-3856) and S. cerevisiae
variety boulardii (Sb, strain CNCM I-3799) decreased the expression
of pro-inflammatory cytokines and chemokines in intestinal epithelial
IPI-2I cells cultured with F4+ ETEC. Results showed that viable Sc
inhibited the ETEC-induced TNF-[alpha] gene expression whereas Sb
did not. In contrast, killed Sc failed to inhibit the expression
of pro-inflammatory genes. This inhibition was dependent on secreted
soluble factors. Sc culture supernatant decreased the TNF-[alpha],
IL-1[alpha], IL-6, IL-8, CXCL2 and CCL20 ETEC-induced mRNA. Furthermore,
Sc culture supernatant filtrated fraction <10 kDa displayed the same
effects excepted for TNF-[alpha]. Thus, our results extended to Sc
(strain CNCM I-3856) the inhibitory effects of some probiotic yeast
strains onto inflammation.},
issn = {0165-2427},
keywords = {Saccharomyces cerevisiae, Enterotoxigenic Escherichia coli, Pig, Intestinal
epithelial cells, Cytokines, Chemokines},
url = {http://www.sciencedirect.com/science/article/pii/S0165242711000432}
}
@ARTICLE{Zanetti2010,
author = {Zanetti, Edoardo and Chiusolo, Arianna and Defazio, Rossella and
Casartelli, Alessandro and Cappelletti, Eleonora and Bocchini, Nicola
and Chiara, Federica and Cristofori, Patrizia and Trevisan, Andrea},
title = {Evaluation of aging influence on renal toxicity caused by segment-specific
nephrotoxicants of the proximal tubule in rat†},
journal = {J. Appl. Toxicol.},
year = {2010},
volume = {30},
pages = {142--150},
number = {2},
abstract = {Abstract Little is known concerning the sensitivity of aged rats to
xenobiotics inducing kidney damage. To increase this knowledge, the
age-dependent response of the kidney to hexachloro-1 : 3-butadiene
(HCBD) or potassium dichromate (chromate) was investigated. Rats
were treated at different ages with a single dose of segment-specific
nephrotoxicants of the proximal tubule, chosen on the basis of their
specificity for S3 and for S1–S2 segments, respectively. The toxicological
impact of these xenobiotics has been evaluated through biochemical
and genomic markers, and histopathological investigation of kidney
samples. HCBD treatment induced tubular necrosis of the S3 segment
of the proximal tubule associated with changes of toxicological markers
unrelated to the age. In contrast, chromate treatment induced an
increased kidney damage related to the rat age. In fact, histopathological
investigation revealed that at 1 month of age tubular vacuolar degeneration
was seen affecting S1–S2 segments of the proximal tubule, whereas
at 3 months of age tubular necrosis occurred in the same segments
associated with tubular dilation of the distal portions. Consistently,
biochemical analysis confirmed a direct correlation among genomic
and biochemical marker variability and animal age. Altogether, the
results show that during aging there is an increased sensitivity
of kidney to chromate but not to HCBD-induced damage and evidence
differential age-related selectivity of rats for nephrotoxic compounds.
Significance for human risk assessment is discussed. Copyright ©
2009 John Wiley & Sons, Ltd.},
issn = {1099-1263},
keywords = {kidney injury molecule-1, osteopontin, hexachloro-1 : 3-butadiene,
potassium dichromate, gene expression, nephrotoxicity},
publisher = {John Wiley \& Sons, Ltd.},
url = {http://dx.doi.org/10.1002/jat.1480}
}
@ARTICLE{Zanetti2005,
author = {Zanetti, Maria Eugenia and Chang, Ing-Feng and Gong, Fangcheng and
Galbraith, David W. and Bailey-Serres, Julia},
title = {Immunopurification of Polyribosomal Complexes of Arabidopsis for
Global Analysis of Gene Expression},
journal = {Plant Physiology},
year = {2005},
volume = {138},
pages = {624--635},
number = {2},
month = jun,
abstract = {Immunoaffinity purification of polyribosomes (polysomes) from crude
leaf extracts of Arabidopsis (Arabidopsis thaliana) was achieved
with transgenic genotypes that overexpress a translational fusion
of a ribosomal protein (RP) with a His6-FLAG dual epitope tag. In
plants with a cauliflower mosaic virus 35S:HF-RPL18 transgene immunopurification
with anti-FLAG agarose beads yielded 60-Svedberg ribosomal subunits,
intact 80-Svedberg monosomes and polysomes. Sucrose density gradient
fractionation of the purified complexes demonstrated that the distribution
of polysome size was similar in crude cell extracts and the purified
complexes. The immunopurified complexes included putative cytosolic
RPs of Arabidopsis and ribosome-associated proteins, as well as full-length
transcripts of high and low abundance. Whole-genome profiling using
long DNA oligonucleotide-based microarrays provided a high level
of reproducibility between polysomal mRNA samples immunopurified
from two independent biological replicates (r approximately 0.90).
Comparison of immunopurified and total cellular RNA samples revealed
that for most of the genes, the mRNAs were associated with the epitope-tagged
polysomal complexes, with an average relative level of association
of 62.06% {+/-} 4.39%. The results demonstrate that the immunopurification
of polysomes can be a valuable tool for the quantification of mRNAs
present in translation complexes in plant cells. This technology
can be extended to evaluation of mRNA populations at the cell- or
tissue-specific level by regulation of the tagged RP with distinct
promoters.},
url = {http://www.plantphysiol.org/cgi/content/abstract/138/2/624}
}
@ARTICLE{Zang2007,
author = {Zang, Hong and Rydén, Mikael and Wåhlen, Kerstin and Dahlman-Wright,
Karin and Arner, Peter and Hirschberg, Angelica Lindén},
title = {Effects of testosterone and estrogen treatment on lipolysis signaling
pathways in subcutaneous adipose tissue of postmenopausal women},
journal = {Fertility and Sterility},
year = {2007},
volume = {88},
pages = {100--106},
number = {1},
month = jul,
abstract = {Objective The aim of this study was to investigate the treatment effects
of testosterone and estrogen on the expression of proteins and genes
involved in adipocyte signal transduction to lipolysis in abdominal
subcutaneous adipose tissue of postmenopausal women.Design An open,
randomized clinical study with parallel group comparison.Setting
Women's health clinical research unit and a research laboratory at
a university hospital.Patient(s) Thirty-six healthy naturally postmenopausal
women.Intervention(s) The participants were randomly given testosterone
undecanoate (40 mg every second day) or estradiol valerate (2 mg
daily) for 3 months.Main Outcome Measure(s) Expression of proteins
and genes involved in adipocyte signal transduction to lipolysis
in abdominal subcutaneous adipose tissue, determined by quantitative
real-time polymerase chain reaction and Western blot, respectively,
and related to plasma glycerol before or during a euglycemic hyperinsulinemic
clamp.Result(s) Testosterone treatment decreased the expression of
hormone-sensitive lipase and increased the expression of phosphodiesterase-3B,
whereas no effect of estrogen was observed. Testosterone-induced
changes in hormone-sensitive lipase expression correlated positively
with corresponding changes in basal or clamp-induced plasma glycerol
concentrations.Conclusion(s) Treatment with testosterone in postmenopausal
women down-regulates hormone-sensitive lipase and up-regulates phosphodiesterase-3B
expressions in abdominal subcutaneous adipose tissue in relation
to changes in vivo of lipolytic activity, which may promote the accumulation
of fat.},
issn = {0015-0282},
keywords = {Testosterone, fat cell, catecholamines, insulin, Western blot, mRNA,
menopause},
url = {http://www.sciencedirect.com/science/article/B6T6K-4NDDT4K-1/2/5bca61240dc1fbd69d4e68c65beabd8b}
}
@ARTICLE{Zangrando2009,
author = {Zangrando, Andrea and Dell'Orto, Marta and te Kronnie, Geertruy and
Basso, Giuseppe},
title = {MLL rearrangements in pediatric acute lymphoblastic and myeloblastic
leukemias: MLL specific and lineage specific signatures},
journal = {BMC Medical Genomics},
year = {2009},
volume = {2},
pages = {36},
number = {1},
abstract = {BACKGROUND:The presence of MLL rearrangements in acute leukemia results
in a complex number of biological modifications that still remain
largely unexplained. Armstrong et al. proposed MLL rearrangement
positive ALL as a distinct subgroup, separated from acute lymphoblastic
(ALL) and myeloblastic leukemia (AML), with a specific gene expression
profile. Here we show that MLL, from both ALL and AML origin, share
a signature identified by a small set of genes suggesting a common
genetic disregulation that could be at the basis of mixed lineage
leukemia in both phenotypes.METHODS:Using Affymetrix® HG-U133 Plus
2.0 platform, gene expression data from 140 (training set) + 78 (test
set) ALL and AML patients with (24+13) and without (116+65) MLL rearrangements
have been investigated performing class comparison (SAM) and class
prediction (PAM) analyses.RESULTS:We identified a MLL translocation-specific
(379 probes) signature and a phenotype-specific (622 probes) signature
which have been tested using unsupervised methods. A final subset
of 14 genes grants the characterization of acute leukemia patients
with and without MLL rearrangements.CONCLUSION:Our study demonstrated
that a small subset of genes identifies MLL-specific rearrangements
and clearly separates acute leukemia samples according to lineage
origin. The subset included well-known genes and newly discovered
markers that identified ALL and AML subgroups, with and without MLL
rearrangements.},
doi = {10.1186/1755-8794-2-36},
issn = {1755-8794},
pubmedid = {19549311},
url = {http://www.biomedcentral.com/1755-8794/2/36}
}
@ARTICLE{Zaragosi2011,
author = {Zaragosi, Laure-Emmanuelle and Wdziekonski, Brigitte and Brigand,
Kevin and Villageois, Phi and Mari, Bernard and Waldmann, Rainer
and Dani, Christian and Barbry, Pascal},
title = {Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific
microRNA and miR-30 as a key regulator of human adipogenesis},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R64},
number = {7},
abstract = {BACKGROUND:In severe obesity, as well as in normal development, the
growth of adipose tissue is the result of an increase in adipocyte
size and numbers, which is underlain by the stimulation of adipogenic
differentiation of precursor cells. A better knowledge of the pathways
that regulate adipogenesis is therefore essential for an improved
understanding of adipose tissue expansion. As microRNAs (miRNAs)
have a critical role in many differentiation processes, our study
aimed to identify the role of miRNA-mediated gene silencing in the
regulation of adipogenic differentiation.RESULTS:We used deep sequencing
to identify small RNAs that are differentially expressed during adipogenesis
of adipose tissue-derived stem cells. This approach revealed the
un-annotated miR-642a-3p as a highly adipocyte-specific miRNA. We
then focused our study on the miR-30 family, which was also up-regulated
during adipogenic differentiation and for which the role in adipogenesis
had not yet been elucidated. Inhibition of the miR-30 family blocked
adipogenesis, whilst over-expression of miR-30a and miR-30d stimulated
this process. We additionally showed that both miR-30a and miR-30d
target the transcription factor RUNX2, and stimulate adipogenesis
via the modulation of this major regulator of osteogenesis.CONCLUSIONS:Overall,
our data suggest that the miR-30 family plays a central role in adipocyte
development. Moreover, as adipose tissue-derived stem cells can differentiate
into either adipocytes or osteoblasts, the down-regulation of the
osteogenesis regulator RUNX2 represents a plausible mechanism by
which miR-30 miRNAs may contribute to adipogenic differentiation
of adipose tissue-derived stem cells.},
doi = {10.1186/gb-2011-12-7-r64},
issn = {1465-6906},
pubmedid = {21767385},
url = {http://genomebiology.com/2011/12/7/R64}
}
@ARTICLE{Zaragoza2006,
author = {Zaragoza, Oscar and Telzak, Andrew and Bryan, Ruth A. and Dadachova,
Ekaterina and Casadevall, Arturo},
title = {The polysaccharide capsule of the pathogenic fungus Cryptococcus
neoformans enlarges by distal growth and is rearranged during budding},
journal = {Molecular Microbiology},
year = {2006},
volume = {59},
pages = {67--83},
number = {1},
abstract = {Summary The capsule of Cryptococcus neoformans can undergo dramatic
enlargement, a phenomenon associated with virulence. A prior study
that used Ab to the capsule as a marker for older capsular material
concluded that capsule growth involved the intermixing of new and
old capsular material with displacement of older capsular polysaccharide
towards the surface. Here we have revisited that question using complement
(C), which binds to capsular polysaccharide covalently, and cannot
redistribute by dissociation and binding at different sites. The
experimental approach involved binding of C to cells with small capsules,
inducing capsule growth, and following the location of C relative
to the cell wall as the capsule enlarged. C remained close to the
cell wall during capsule growth, indicating that capsule enlargement
occurred by addition of new polysaccharide near the capsule edge.
This conclusion was confirmed by an independent method that employed
radioactive metabolic labelling of newly synthesized capsule with
3H-mannose followed by gradual capsular stripping with γ-radiation.
Capsule growth proceeded to a certain size, which was a function
of cell size, and was not degraded when the cells were transferred
to a non-inducing medium. During budding, an opening appeared in
the capsule of the mother cell that permitted the nascent bud to
separate. Scanning EM suggested that a physical separation formed
between the capsules of the mother and daughter cells during budding,
which may avoid mixture between both capsules. Our results indicate
that C. neoformans capsular enlargement also occurs by apical growth
and that budding results in capsular rearrangements.},
issn = {1365-2958},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2005.04928.x}
}
@ARTICLE{Zarlenga2004,
author = {Zarlenga, Dante S. and Dawson, Harry and Kringel, Helene and Solano-Aguilar,
Gloria and Urban, Joseph F.},
title = {Molecular cloning of the Swine IL-4 receptor [alpha] and IL-13 receptor
1-chains: effects of experimental Toxoplasma gondii, Ascaris suum
and Trichuris suis infections on tissue mRNA levels},
journal = {Veterinary Immunology and Immunopathology},
year = {2004},
volume = {101},
pages = {223--234},
number = {3-4},
month = oct,
abstract = {IL-4 and IL-13 are multi-functional cytokines with overlapping roles
in the host defense against infection. Equally important in the regulation
of IL-4 and IL-13 are their associated receptors. Though, their functional
receptor complexes and signaling pathways are intricate and in some
cases, share common elements, the specificity of the responses, nonetheless,
resides in the structure and binding of the [alpha]-chain components.
This report presents the cloning of the swine receptors IL-4R[alpha]
and IL-13R[alpha]1 and the effects of parasite infection on their
transcription. Pairwise alignment of predicted amino acid sequences
indicates that the swine IL-13R[alpha]1 is 86, 83, and 72% similar
to canine, human and mouse sequences, respectively. Amino acid sequence
conservation is appreciably lower between the swine IL-4R[alpha]
sequence and those from equine (72%), human (66%), and mouse (49%);
however, noteworthy similarities were observed in their overall predicted
secondary structures predominantly among the swine, equine, and human
homologues. Relative levels of receptor mRNA in tissues from swine
experimentally infected with the protozoan, Toxoplasma gondii (T.
gondii) or the nematodes Ascaris suum (A. suum) or Trichuris suis
(T. suis), which are known to induce Th1 or Th2 host responses, respectively,
were measured by real-time PCR. Results indicated that within 14
days following infection, overall mRNA levels for IL-4R[alpha] and
IL-13R[alpha]1 were elevated in T. gondii-infected animals and reduced
in A. suum-infected animals. Levels of swIL-4R[alpha] and swIL-13R[alpha]1
mRNA in T. suis-infected animals varied coincidentally with the course
of the infection and the location of the analyzed tissue.},
issn = {0165-2427},
keywords = {IL-4 receptor, IL-13 receptor, Swine, Real-time PCR, Gene expression},
url = {http://www.sciencedirect.com/science/article/B6TD5-4CXDR61-1/2/734c8948b7c14b72234e14424c68ae8e}
}
@ARTICLE{Zarnegar2006,
author = {Zarnegar, Parisa and Persson, Anders I. and Ming, Yu and Terenius,
Lars},
title = {Opioid-induced regulation of gene expression in PC12 cells stably
transfected with mu-opioid receptor},
journal = {Neuroscience Letters},
year = {2006},
volume = {396},
pages = {197--201},
number = {3},
month = apr,
abstract = {It has been postulated that opiates induce addictive behaviour via
changes in gene expression. PC12 cells were stably transfected with
the recombinant human mu-opioid receptor (MOR) to study opioid-induced
gene expression. Expression was verified by binding assay, immunocytochemistry,
and immunblotting experiments. Forskolin-induced cAMP formation was
inhibited by [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO 1 [mu]M),
a specific MOR agonist. This effect was completely antagonized by
naloxone. By using cDNA arrays, including approximately 1200 well-defined
genes normally expressed in neural tissue, we monitored semi-quantitative
changes in gene expression after 3 h short-term exposure to DAMGO.
Incubation with DAMGO increased mRNA levels for 13 genes and down-regulated
13 other genes. Annexin V, RGS4 and CREB genes showed pronounced
increase in expression after stimulation with DAMGO. Quantitative
RT-PCR confirmed that DAMGO increased mRNA levels of Annexin V, an
apoptosis-induced gene. We suggest that the PC12 cell transfected
with the recombinant human MOR is a useful tool for identification
of opioid-induced genes that may provide information on opiate effects
of relevance for dependence.},
issn = {0304-3940},
keywords = {Gene-array, Gene expression, Mu-opioid receptor, Opioid, PC12 cells},
url = {http://www.sciencedirect.com/science/article/B6T0G-4HWX9YG-4/2/8f92cd31595539653b1613620643d44e}
}
@ARTICLE{Zaslavsky2010,
author = {Zaslavsky, Elena and Hershberg, Uri and Seto, Jeremy and Pham, Alissa
M. and Marquez, Susanna and Duke, Jamie L. and Wetmur, James G. and
tenOever, Benjamin R. and Sealfon, Stuart C. and Kleinstein, Steven
H.},
title = {Antiviral Response Dictated by Choreographed Cascade of Transcription
Factors},
journal = {J. Immunol.},
year = {2010},
volume = {184},
pages = {2908--2917},
number = {6},
month = mar,
abstract = {The dendritic cell (DC) is a master regulator of immune responses.
Pathogenic viruses subvert normal immune function in DCs through
the expression of immune antagonists. Understanding how these antagonists
interact with the host immune system requires knowledge of the underlying
genetic regulatory network that operates during an uninhibited antiviral
response. To isolate and identify this network, we studied DCs infected
with Newcastle disease virus, which is able to stimulate innate immunity
and DC maturation through activation of RIG-I signaling, but lacks
the ability to evade the human IFN response. To analyze this experimental
model, we developed a new approach integrating genome-wide expression
kinetics and time-dependent promoter analysis. We found that the
genetic program underlying the antiviral cell-state transition during
the first 18 h postinfection could be explained by a single convergent
regulatory network. Gene expression changes were driven by a stepwise
multifactor cascading control mechanism, where the specific transcription
factors controlling expression changed over time. Within this network,
most individual genes were regulated by multiple factors, indicating
robustness against virus-encoded immune evasion genes. In addition
to effectively recapitulating current biological knowledge, we predicted,
and validated experimentally, antiviral roles for several novel transcription
factors. More generally, our results show how a genetic program can
be temporally controlled through a single regulatory network to achieve
the large-scale genetic reprogramming characteristic of cell-state
transitions.},
url = {http://www.jimmunol.org/cgi/content/abstract/184/6/2908}
}
@ARTICLE{Zaslona2009,
author = {Zaslona, Zbigniew and Wilhelm, Jochen and Cakarova, Lidija and Marsh,
Leigh and Seeger, Werner and Lohmeyer, Jürgen and von Wulffen, Werner},
title = {Transcriptome profiling of primary murine monocytes, lung macrophages
and lung dendritic cells reveals a distinct expression of genes involved
in cell trafficking},
journal = {Respiratory Research},
year = {2009},
volume = {10},
pages = {2},
number = {1},
abstract = {BACKGROUND:Peripheral blood monocytes (PBMo) originate from the bone
marrow, circulate in the blood and emigrate into various organs where
they differentiate into tissue resident cellular phenotypes of the
mononuclear phagocyte system, including macrophages (M?) and dendritic
cells (DC). Like in other organs, this emigration and differentiation
process is essential to replenish the mononuclear phagocyte pool
in the lung under both inflammatory and non-inflammatory steady-state
conditions. While many studies have addressed inflammation-driven
monocyte trafficking to the lung, the emigration and pulmonary differentiation
of PBMo under non-inflammatory conditions is much less understood.METHODS:In
order to assess the transcriptional profile of circulating and lung
resident mononuclear phagocyte phenotypes, PBMo, lung M? and lung
DC from naïve mice were flow-sorted to high purity, and their gene
expression was compared by DNA microarrays on a genome-wide scale.
Differential regulation of selected genes was validated by quantitative
PCR and on protein level by flow cytometry.RESULTS:Differentially-expressed
genes related to cell traffic were selected and grouped into the
clusters (i) matrix metallopeptidases, (ii) chemokines/chemokine
receptors, and (iii) integrins. Expression profiles of clustered
genes were further assessed at the mRNA and protein levels in subsets
of circulating PBMo (GR1- vs GR1+) and lung resident macrophages
(alveolar vs interstitial M?). Our data identify differentially activated
genetic programs in circulating monocytes and their lung descendents.
Lung DC activate an extremely diverse set of gene families but largely
preserve a mobile cell profile with high expression levels of integrin
and chemokine/chemokine receptors. In contrast, interstitial and
even more pronounced alveolar M?, stepwise downregulate gene expression
of these traffic relevant communication molecules, but strongly upregulate
a distinct set of matrix metallopetidases potentially involved in
tissue invasion and remodeling.CONCLUSION:Our data provide new insight
in the changes of the genetic profiles of PBMo and their lung descendents,
namely DC and M? under non-inflammatory, steady-state conditions.
These findings will help to better understand the complex relations
within the mononuclear phagocyte pool of the lung.},
doi = {10.1186/1465-9921-10-2},
issn = {1465-9921},
pubmedid = {19149869},
url = {http://respiratory-research.com/content/10/1/2}
}
@ARTICLE{Zaura2009,
author = {Zaura, Egija and Keijser, Bart and Huse, Susan and Crielaard, Wim},
title = {Defining the healthy "core microbiome" of oral microbial communities},
journal = {BMC Microbiology},
year = {2009},
volume = {9},
pages = {259},
number = {1},
abstract = {BACKGROUND:Most studies examining the commensal human oral microbiome
are focused on disease or are limited in methodology. In order to
diagnose and treat diseases at an early and reversible stage an in-depth
definition of health is indispensible. The aim of this study therefore
was to define the healthy oral microbiome using recent advances in
sequencing technology (454 pyrosequencing).RESULTS:We sampled and
sequenced microbiomes from several intraoral niches (dental surfaces,
cheek, hard palate, tongue and saliva) in three healthy individuals.
Within an individual oral cavity, we found over 3600 unique sequences,
over 500 different OTUs or "species-level" phylotypes (sequences
that clustered at 3% genetic difference) and 88 - 104 higher taxa
(genus or more inclusive taxon). The predominant taxa belonged to
Firmicutes (genus Streptococcus, family Veillonellaceae, genus Granulicatella),
Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus
Corynebacterium, Rothia, Actinomyces), Bacteroidetes (genus Prevotella,
Capnocytophaga, Porphyromonas) and Fusobacteria (genus Fusobacterium).Each
individual sample harboured on average 266 "species-level" phylotypes
(SD 67; range 123 - 326) with cheek samples being the least diverse
and the dental samples from approximal surfaces showing the highest
diversity. Principal component analysis discriminated the profiles
of the samples originating from shedding surfaces (mucosa of tongue,
cheek and palate) from the samples that were obtained from solid
surfaces (teeth).There was a large overlap in the higher taxa, "species-level"
phylotypes and unique sequences among the three microbiomes: 84%
of the higher taxa, 75% of the OTUs and 65% of the unique sequences
were present in at least two of the three microbiomes. The three
individuals shared 1660 of 6315 unique sequences. These 1660 sequences
(the "core microbiome") contributed 66% of the reads. The overlapping
OTUs contributed to 94% of the reads, while nearly all reads (99.8%)
belonged to the shared higher taxa.CONCLUSIONS:We obtained the first
insight into the diversity and uniqueness of individual oral microbiomes
at a resolution of next-generation sequencing. We showed that a major
proportion of bacterial sequences of unrelated healthy individuals
is identical, supporting the concept of a core microbiome at health.},
doi = {10.1186/1471-2180-9-259},
issn = {1471-2180},
pubmedid = {20003481},
url = {http://www.biomedcentral.com/1471-2180/9/259}
}
@ARTICLE{Zaza2008,
author = {Zaza, Gianluigi and Pontrelli, Paola and Pertosa, Giovanni and Granata,
Simona and Rossini, Michele and Porreca, Silvia and Staal, Frank
J. T. and Gesualdo, Loreto and Grandaliano, Giuseppe and Schena,
Francesco Paolo},
title = {Dialysis-related systemic microinflammation is associated with specific
genomic patterns},
journal = {Nephrol. Dial. Transplant.},
year = {2008},
volume = {23},
pages = {1673--1681},
number = {5},
month = may,
abstract = {Background. Although several reports have focused on the clinical
importance of the systemic microinflammatory state in the uraemic
population, the relationship between the activation of a specific
transcriptome and the development of this condition is still not
completely defined. Methods. Thirty haemodialysis (HD), 30 peritoneal
dialysis (PD) and 30 chronic kidney disease (CKD) patients were enrolled
in our study. For all patients, serum C-reactive protein (CRP) and
ferritin levels were determined. In addition, the expression level
of 234 inflammatory responses and oxidative stress pathway genes
was measured, using oligonucleotide microarray chips (HG-U133A, Affymetrix),
in peripheral blood mononuclear cells of 24 randomly selected patients
(8 HD, 8 PD and 8 CKD). Results. HD patients demonstrated higher
CRP and ferritin levels compared to PD and CKD patients (P < 0.001).
Statistical analysis identified 10 genes able to discriminate CKD
from HD and PD patients (FDR = 5%, P < 0.001) and significantly correlated
to CRP levels. All together, these genes were able to predict inflammation
with an accuracy of 87% (P < 0.001). Among the selected genes there
were those encoding for key regulators of inflammation and oxidative
stress (e.g. RELA, GSS). Interestingly, only three inflammatory genes
(MIF, IL8RB and CXCL12) were still significantly associated with
inflammation when included in a multivariate analysis. RT-PCR for
RELA, MIF, CXCL12 and western blots for IL8RB and GSS, using 66 patients,
validated the microarray results. Conclusions. This study may help
to better understand the physiopathology of the systemic inflammatory
state in CKD and dialysis patients and to identify new target genes
potentially useful for future bio-molecular studies and therapeutic
approaches.},
url = {http://ndt.oxfordjournals.org/cgi/content/abstract/23/5/1673}
}
@ARTICLE{Zeaiter2008,
author = {Zeaiter, Zaher and Cohen, David and Müsch, Anne and Bagnoli, Fabio
and Covacci, Antonello and Stein, Markus},
title = {Analysis of detergent-resistant membranes of Helicobacter pylori
infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b
in CagA-mediated disruption of cellular polarity},
journal = {Cellular Microbiology},
year = {2008},
volume = {10},
pages = {781--794},
number = {3},
abstract = {Summary Detergent-resistant membranes of eukaryotic cells are enriched
in many important cellular signalling molecules and frequently targeted
by bacterial pathogens. To learn more about pathogenic mechanisms
of Helicobacter pylori and to elucidate novel effects on host epithelial
cells, we investigated how bacterial co-cultivation changes the protein
composition of detergent-resistant membranes of gastric adenocarcinoma
(AGS) tissue culture cells. Using iTRAQ (isobaric tags for relative
and absolute quantification) analysis we identified several cellular
proteins, which are potentially related to H. pylori virulence. One
of the proteins, which showed a significant infection-dependent increase
in detergent resistance, was the polarity-associated serine/threonine
kinase MARK2 (EMK1/Par-1b). We demonstrate that H. pylori causes
the recruitment of MARK2 from the cytosol to the plasma membrane,
where it colocalizes with the bacteria and interacts with CagA. Using
Mardin Darby Canine Kidney (MDCK) monolayers and a three-dimensional
MDCK tissue culture model we showed that association of CagA with
MARK2 not only causes disruption of apical junctions, but also inhibition
of tubulogenesis and cell differentiation.},
issn = {1462-5822},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2007.01084.x}
}
@ARTICLE{Zee2011,
author = {van der Zee, Julie and Van Langenhove, Tim and Kleinberger, Gernot
and Sleegers, Kristel and Engelborghs, Sebastiaan and Vandenberghe,
Rik and Santens, Patrick and Van den Broeck, Marleen and Joris, Geert
and Brys, Jolien and Mattheijssens, Maria and Peeters, Karin and
Cras, Patrick and De Deyn, Peter P. and Cruts, Marc and Van Broeckhoven,
Christine},
title = {TMEM106B is associated with frontotemporal lobar degeneration in
a clinically diagnosed patient cohort},
journal = {Brain},
year = {2011},
volume = {134},
pages = {808--815},
number = {3},
month = mar,
abstract = {In a genome-wide association study of frontotemporal lobar degeneration
with pathological inclusions of TAR DNA-binding protein, significant
association was obtained with three single nucleotide polymorphisms
at 7p21.3, in a region encompassing the gene TMEM106B. This study
also suggested a potential modifying effect of TMEM106B on disease
since the association was strongest in progranulin mutation carriers.
Further, the risk effect seemed to correlate with increased TMEM106B
expression in patients. In the present study, we sought to replicate
these three findings using an independent Flanders-Belgian cohort
of primarily clinically diagnosed patients with frontotemporal lobar
degeneration (n = 288). We were able to confirm the association with
TMEM106B with a P-value of 0.008 for rs1990622, the top marker from
the genome-wide association study [odds ratio 0.75 (95% confidence
interval 0.61-0.93)]. Further, high-density single nucleotide polymorphism
mapping suggested that the association was solely driven by the gene
TMEM106B. Homozygous carriers of the TMEM106B protective alleles
had a 50% reduced risk of developing frontotemporal lobar degeneration.
However, we were unable to detect a modifying effect of the TMEM106B
single nucleotide polymorphisms on onset age in progranulin mutation
carriers belonging to an extended, clinical and pathological well-documented
founder family segregating a progranulin null mutation. Also, we
could not observe significant differences in messenger RNA expression
between patients and control individuals in lymphoblast cell lines
and in brain frontal cortex. In conclusion, we replicated the genetic
TMEM106B association in a primarily clinically diagnosed cohort of
patients with frontotemporal lobar degeneration from Flanders-Belgium.
Additional studies are needed to unravel the molecular role of TMEM106B
in disease onset and pathogenesis.},
comment = {10.1093/brain/awr007},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/134/3/808}
}
@ARTICLE{Zeidler-Erdely2010,
author = {Zeidler-Erdely, Patti and Kashon, Michael and Li, Shengqiao and Antonini,
James},
title = {Response of the mouse lung transcriptome to welding fume: effects
of stainless and mild steel fumes on lung gene expression in A/J
and C57BL/6J mice},
journal = {Respiratory Research},
year = {2010},
volume = {11},
pages = {70},
number = {1},
abstract = {BACKGROUND:Debate exists as to whether welding fume is carcinogenic,
but epidemiological evidence suggests that welders are an at risk
population for the development of lung cancer. Recently, we found
that exposure to welding fume caused an acutely greater and prolonged
lung inflammatory response in lung tumor susceptible A/J versus resistant
C57BL/6J (B6) mice and a trend for increased tumor incidence after
stainless steel (SS) fume exposure. Here, our objective was to examine
potential strain-dependent differences in the regulation and resolution
of the lung inflammatory response induced by carcinogenic (Cr and
Ni abundant) or non-carcinogenic (iron abundant) metal-containing
welding fumes at the transcriptome level.METHODS:Mice were exposed
four times by pharyngeal aspiration to 5 mg/kg iron abundant gas
metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or
vehicle and were euthanized 4 and 16 weeks after the last exposure.
Whole lung microarray using Illumina Mouse Ref-8 expression beadchips
was done.RESULTS:Overall, we found that tumor susceptibility was
associated with a more marked transcriptional response to both GMA-MS
and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed
that gene regulation and expression in the top molecular networks
differed between the strains at both time points post-exposure. Interestingly,
a common finding between the strains was that GMA-MS fume exposure
altered behavioral gene networks. In contrast, GMA-SS fume exposure
chronically upregulated chemotactic and immunomodulatory genes such
as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed
B6 mouse, genes that initially downregulated cellular movement, hematological
system development/function and immune response were involved at
both time points post-exposure. However, at 16 weeks, a transcriptional
switch to an upregulation for neutrophil chemotactic genes was found
and included genes such as S100A8, S100A9 and MMP9.CONCLUSIONS:Collectively,
our results demonstrate that lung tumor susceptibility may predispose
the A/J strain to a prolonged dysregulation of immunomodulatory genes,
thereby delaying the recovery from welding fume-induced lung inflammation.
Additionally, our results provide unique insight into strain- and
welding fume-dependent genetic factors involved in the lung response
to welding fume.},
doi = {10.1186/1465-9921-11-70},
issn = {1465-9921},
pubmedid = {20525249},
url = {http://respiratory-research.com/content/11/1/70}
}
@ARTICLE{Zeiger2010,
author = {Zeiger, Ulrike and Khurana, Tejvir S.},
title = {Distinctive patterns of microRNA expression in extraocular muscles},
journal = {Physiol Genomics},
year = {2010},
volume = {41},
pages = {289--296},
number = {3},
month = may,
abstract = {The extraocular muscles (EOMs) are a unique group of muscles that
are anatomically and physiologically distinct from other muscles.
We and others have shown that EOMs have a unique transcriptome and
proteome. Here we investigated the expression pattern of microRNAs
(miRNAs), as they may play a role in generating the unique EOM allotype.
We isolated RNA and screened LC Sciences miRNA microarrays covering
the sequences of miRBase 10.0 to define the microRNAome of normal
mouse EOM and tibialis anterior (TA) limb muscle. Seventy-four miRNAs
were found to be differentially regulated (P value <0.05) of which
31 (14 upregulated, 17 downregulated) were differentially regulated
at signal strength >500. Muscle-specific miRNAs miR-206 and miR-499
were upregulated and miR-1, miR-133a, and miR-133b were downregulated
in EOM. Quantitative PCR (qPCR) analysis was used to validate the
differential expression. Bioinformatic tools were used to identify
potential miRNA-mRNA-protein interactions and integrate data with
previous transcriptome and proteomic profiling data. Luciferase assays
using cotransfection of precursor miRNAs with reporter constructs
containing the 3'-untranslated region of predicted target genes were
used to validate targeting by identified miRNAs. The definition of
the EOM microRNAome complements existing transcriptome and proteome
data about the molecular makeup of EOM and provides further insight
into regulation of muscle genes. These data will also help to further
explain the unique EOM muscle allotype and its differential sensitivity
to diseases such as Duchenne muscular dystrophy and may assist in
development of therapeutic strategies.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/41/3/289}
}
@ARTICLE{Zeilstra2008,
author = {Zeilstra, Jurrit and Joosten, Sander P.J. and Dokter, Maarten and
Verwiel, Eugene and Spaargaren, Marcel and Pals, Steven T.},
title = {Deletion of the WNT Target and Cancer Stem Cell Marker CD44 in Apc(Min/+)
Mice Attenuates Intestinal Tumorigenesis},
journal = {Cancer Res.},
year = {2008},
volume = {68},
pages = {3655--3661},
number = {10},
month = may,
abstract = {Mutation of the genes encoding the WNT signaling components adenomatous
polyposis coli or {beta}-catenin plays a critical role in the initiation
of colorectal cancer. These mutations cause constitutively active
{beta}-catenin/TCF-mediated transcription, driving the transformation
of intestinal crypts to colorectal cancer precursor lesions, called
dysplastic aberrant crypt foci. CD44 is a prominent WNT signaling
target in the intestine and is selectively expressed on the renewing
epithelial cells lining the crypts. The expression of CD44 is dramatically
increased in aberrant crypt foci in both humans and tumor-susceptible
ApcMin/+ mice, suggesting a role for CD44 in intestinal tumorigenesis.
To study this role, we crossed C57BL/6J-Cd44-/- mice with C57BL/6J-ApcMin/+
mice. Compared with C57BL/6J-Cd44+/+/ApcMin/+ mice, C57BL/6J-Cd44-/-/ApcMin/+
mice showed an almost 50% reduction in the number of intestinal adenomas.
This reduction was primarily caused by a decrease in the formation
of aberrant crypts, implying the involvement of CD44 in tumor initiation.
The absence of CD44 in the normal (nonneoplastic) crypts of Cd44-/-/ApcMin/+
mice did not alter the proliferative capacity and size of the intestinal
stem cell and transit-amplifying compartments. However, compared
with Cd44+/+/ApcMin/+ mice, Cd44-/-/ApcMin/+ showed an increase in
the number of apoptotic epithelial cells at the base of the crypt
which correlated with an increased expression of the proapoptotic
genes Bok and Dr6. Our results show an important role for CD44 in
intestinal tumorigenesis and suggest that CD44 does not affect proliferation
but is involved in the control of the balance between survival and
apoptosis in the intestinal crypt. [Cancer Res 2008;68(10):3655-61]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/10/3655}
}
@ARTICLE{Zeisberger2010,
author = {Zeisberger, Steffen M. and Zoller, Stefan and Riegel, Mariluce and
Chen, Shuhua and Krenning, Guido and Harmsen, Martin C. and Sachinidis,
Agapios and Zisch, Andreas H.},
title = {Optimization of the culturing conditions of human umbilical cord
blood-derived endothelial colony-forming cells under xeno-free conditions
applying a transcriptomic approach},
journal = {Genes to Cells},
year = {2010},
volume = {15},
pages = {671--687},
number = {7},
abstract = {Establishment of fetal bovine serum (FBS)-free cell culture conditions
is essential for transplantation therapies. Blood-derived endothelial
colony-forming cells (ECFCs) are potential candidates for regenerative
medicine applications. ECFCs were isolated from term umbilical cord
blood units and characterized by flow cytometry, capillary formation
and responsiveness to cytokines. ECFCs were expanded under standard,
FBS-containing endothelial medium, or transferred to chemically defined
endothelial media without FBS. Microarray expression profiling was
applied to compare the transcriptome profiles in FBS-containing versus
FBS-free culture. ECFC outgrowth in standard medium was successful
in 92% of cord blood units. The karyotype of expanded ECFCs remained
normal. Without FBS, ECFC initiation and expansion failed. Modest
proliferation, changes in cell morphology and organization and cell
death have been observed after passaging. Gene ontology analysis
revealed a broad down-regulation of genes involved in cell cycle
progression and up-regulation of genes involved in stress response
and apoptosis. Interestingly, genes participating in lipid biosynthesis
were markedly up-regulated. Detection of several endothelial cell-specific
marker genes showed the maintenance of the endothelial cell characteristics
during serum-free culture. Although ECFCs maintain their endothelial
characteristics during serum-free culturing, they could not be expanded.
Additional supply of FBS-free media with lipid concentrates might
increase the ECFC survival.},
issn = {1365-2443},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2443.2010.01409.x}
}
@ARTICLE{Zelazny2009,
author = {Zelazny, Adrian M. and Root, Jeremy M. and Shea, Yvonne R. and Colombo,
Rhonda E. and Shamputa, Isdore C. and Stock, Frida and Conlan, Sean
and McNulty, Steven and Brown-Elliott, Barbara A. and Wallace, Richard
J., Jr. and Olivier, Kenneth N. and Holland, Steven M. and Sampaio,
Elizabeth P.},
title = {Cohort Study of Molecular Identification and Typing of Mycobacterium
abscessus, Mycobacterium massiliense, and Mycobacterium bolletii},
journal = {J. Clin. Microbiol.},
year = {2009},
volume = {47},
pages = {1985--1995},
number = {7},
month = jul,
abstract = {Mycobacterium abscessus is the most common cause of rapidly growing
mycobacterial chronic lung disease. Recently, two new M. abscessus-related
species, M. massiliense and M. bolletii, have been described. Health
care-associated outbreaks have recently been investigated by the
use of molecular identification and typing tools; however, very little
is known about the natural epidemiology and pathogenicity of M. massiliense
or M. bolletii outside of outbreak situations. The differentiation
of these two species from M. abscessus is difficult and relies on
the sequencing of one or more housekeeping genes. We performed extensive
molecular identification and typing of 42 clinical isolates of M.
abscessus, M. massiliense, and M. bolletii from patients monitored
at the NIH between 1999 and 2007. The corresponding clinical data
were also examined. Partial sequencing of rpoB, hsp65, and secA led
to the unambiguous identification of 26 M. abscessus isolates, 7
M. massiliense isolates, and 2 M. bolletii isolates. The identification
results for seven other isolates were ambiguous and warranted further
sequencing and an integrated phylogenetic analysis. Strain relatedness
was assessed by repetitive-sequence-based PCR (rep-PCR) and pulsed-field
gel electrophoresis (PFGE), which showed the characteristic clonal
groups for each species. Five isolates with ambiguous species identities
as M. abscessus-M. massiliense by rpoB, hsp65, and secA sequencing
clustered as a distinct group by rep-PCR and PFGE together with the
M. massiliense type strain. Overall, the clinical manifestations
of disease caused by each species were similar. In summary, a multilocus
sequencing approach (not just rpoB partial sequencing) is required
for division of M. abscessus and closely related species. Molecular
typing complements sequence-based identification and provides information
on prevalent clones with possible relevant clinical aspects.},
url = {http://jcm.asm.org/cgi/content/abstract/47/7/1985}
}
@ARTICLE{Zelck2005,
author = {Zelck, U.E. and Janje, B. and Schneider, O.},
title = {Superoxide dismutase expression and H2O2 production by hemocytes
of the trematode intermediate host Lymnaea stagnalis (Gastropoda)},
journal = {Developmental \& Comparative Immunology},
year = {2005},
volume = {29},
pages = {305--314},
number = {4},
abstract = {Snail hemocytes mobilise ROS-generating enzymes during oxidative burst
similar to those of mammalian leukocytes. We report herein the identification
of an inducible Cu/Zn superoxide dismutase, which converts O2- to
H2O2, in hemocytes of the pond snail Lymnaea stagnalis. The deduced
amino acid sequence with all characteristic residues (His44,46,61,69,78
and 118, Asp81, Cys55/144, Arg141 and the Greek Key loop region Glu119-Leu/Val142)
includes an open reading frame of 155 AA. Changes in Cu/ZnSOD gene
expression induced by stimulation with Zymosan or trematode larvae
were examined in a time course. Activated hemocytes significantly
up-regulate Cu/ZnSOD expression during 2-48 h upon stimulation with
the maximal induction at 45 min during phagocytosis and at 12 h during
encapsulations. This increase in Cu/ZnSOD expression paralleled the
increasing production of hydrogen peroxide by hemocytes. Thus, intracellular
or extracellular targets elicit an induced expression of Cu/ZnSOD
and the generation of elevated amounts of hydrogen peroxide by L.
stagnalis hemocytes, reflecting a significant activation of their
host defense function.},
issn = {0145-305X},
keywords = {Cu/Zn superoxide dismutase, Hemocyte, Hydrogen peroxide, Expression
regulation, Lymnaea stagnalis},
url = {http://www.sciencedirect.com/science/article/B6T5X-4DKDTSJ-2/2/e0dee7a8cdacad8525ec23b6b17f206d}
}
@ARTICLE{Zelent2006,
author = {Zelent, Dorothy and Golson, Maria L. and Koeberlein, Brigitte and
Quintens, Roel and van Lommel, Leentje and Buettger, Carol and Weik-Collins,
Heather and Taub, Rebecca and Grimsby, Joseph and Schuit, Frans and
Kaestner, Klaus H. and Matschinsky, Franz M.},
title = {A Glucose Sensor Role for Glucokinase in Anterior Pituitary Cells},
journal = {Diabetes},
year = {2006},
volume = {55},
pages = {1923--1929},
number = {7},
month = jul,
abstract = {Enzymatic activity of glucokinase was demonstrated, quantitated, and
characterized kinetically in rat and mouse pituitary extracts using
a highly specific and sensitive spectrometric assay. A previously
proposed hypothesis that the glucokinase gene might be expressed
in the pituitary corticotrophic cells was therefore reexamined using
mRNA in situ hybridization and immunohistochemical techniques. No
evidence was found that corticotrophs are glucokinase positive, and
the identity of glucokinase-expressing cells remains to be determined.
The findings do, however, suggest a novel hypothesis that a critical
subgroup of anterior pituitary cells might function as glucose sensor
cells and that direct fuel regulation of such cells may modify the
classical indirect neuroendocrine pathways that are known to control
hormone secretion from anterior pituitary cells.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/55/7/1923}
}
@ARTICLE{Zelinkova2008,
author = {Zelinkova, Zuzana and van Beelen, Astrid J. and de Kort, Floor and
Moerland, Perry D. and van Themaat, Emiel Ver Loren and Velde, Anje
A.te and van Deventer, Sander J. and de Jong, Esther C. and Hommes,
Daniel W.},
title = {Muramyl dipeptide–induced differential gene expression in NOD2
mutant and wild-type crohn's disease patient–derived dendritic
cells},
journal = {Inflamm Bowel Dis},
year = {2008},
volume = {14},
pages = {186--194},
number = {2},
abstract = {Abstract 10.1002/ibd.20308.abs Background: Mutations in the gene encoding
the nucleotide-binding oligomerization domain 2 (NOD2) protein are
associated with Crohn's disease (CD), but the mechanism underlying
this is not completely understood. To study the mechanism of CD resulting
from NOD2 mutations, we analyzed NOD2-dependent whole-genome expression
profiles of patient-derived antigen-presenting cells. Patients and
Methods: Monocyte-derived dendritic cells (DCs) from CD carriers
of double-dose NOD2 mutations, wild-type CD patients, and wild-type
healthy volunteers were stimulated with the NOD2 ligand muramyl dipeptide.
Whole-genome microarrays were used to assess the differential gene
expression. The clustering of significantly changed genes was analyzed
by online gene ontology mapping software. Results: In the DCs from
the wild-type CD patient group, 683 genes were significantly changed,
with most of the genes clustering in the pathways of inflammatory
response. In addition, a significant number of genes clustered in
the apoptosis regulation–related pathway. In the DCs from the healthy
volunteer group, only 50 genes were significantly changed, predominantly
those belonging to the response to pathogen pathway. Analysis of
differentially expressed gene ontology pathways in the DCs from the
NOD2 mutant CD patient group showed that the transcription of pathogen
response genes was absent. In this group, 298 genes were significantly
changed, predominantly clustering in the negative apoptosis regulation
and cell organization and biogenesis pathways. Conclusions: Our results
suggest that NOD2 mutations may result in perpetuation of mucosal
inflammation through insufficient pathogen elimination. Further,
these observations implicate a possible role of defective regulation
of dendritic cell apoptosis in CD pathogenesis. (Inflamm Bowel Dis
2007)},
issn = {1536-4844},
keywords = {NOD2, apoptosis, dendritic cells, Crohn's disease},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ibd.20308}
}
@ARTICLE{Zeller2005,
author = {Zeller, Tanja and Moskvin, Oleg V. and Li, Kuanyu and Klug, Gabriele
and Gomelsky, Mark},
title = {Transcriptome and Physiological Responses to Hydrogen Peroxide of
the Facultatively Phototrophic Bacterium Rhodobacter sphaeroides},
journal = {J. Bacteriol.},
year = {2005},
volume = {187},
pages = {7232--7242},
number = {21},
month = nov,
abstract = {The transcriptome responses to hydrogen peroxide, H2O2, of the facultatively
phototrophic bacterium Rhodobacter sphaeroides grown under semiaerobic
conditions were investigated. At 7 min after the addition of 1 mM
H2O2, the expression of approximately 9% of all genes (total, 394)
was changed reliably by at least twofold. At 30 min, the number of
genes (total, 88) and the magnitude of expression changes were much
lower, indicating rapid recovery from stress. Two types of responses
were observed: (i) an H2O2 stress response per se and (ii) a shift
to high-oxygen metabolism. The former response involved the upregulation
of genes for H2O2 detoxification, protein folding and proteolysis,
DNA damage repair, iron transport and storage, iron-sulfur cluster
repair, and the downregulation of genes for protein translation,
motility, and cell wall and lipopolysaccharide synthesis. The shift
to high-oxygen metabolism was evident from the differential regulation
of genes for aerobic electron transport chain components and the
downregulation of tetrapyrrole biosynthesis and photosystem genes.
The abundance of photosynthetic complexes was decreased upon prolonged
exposure of R. sphaeroides to H2O2, thus confirming the physiological
significance of the transcriptome data. The regulatory pathways mediating
the shift to high-oxygen metabolism were investigated. They involved
the anaerobic activator FnrL and the antirepressor-repressor AppA-PpsR
system. The transcription of FnrL-dependent genes was down at 7 min,
apparently due to the transient inactivation by H2O2 of the iron-sulfur
cluster of FnrL. The transcription of the AppA-PpsR-dependent genes
was down at 30 min, apparently due to the significant decrease in
appA mRNA.},
url = {http://jb.asm.org/cgi/content/abstract/187/21/7232}
}
@ARTICLE{Zellmer2009,
author = {Zellmer, Sebastian and Sickinger, Stephan and Schmidt-Heck, Wolfgang
and Guthke, Reinhard and Gebhardt, Rolf},
title = {Heterogeneous expression of suppressor of cytokine signalling 2 (SOCS-2)
in liver tissue},
journal = {Journal of Anatomy},
year = {2009},
volume = {215},
pages = {176--183},
number = {2},
abstract = {Abstract Suppressor of cytokine signalling 2 (SOCS-2), a dual effector
of growth hormone signalling, was found to be heterogeneously expressed
in murine liver parenchyma. Data from Affymetrix gene arrays, confirmed
by quantitative RT-PCR using preparations of periportal and pericentral
hepatocyte subpopulations as well as immunohistochemical detection,
showed a preferential expression of SOCS-2 in pericentral hepatocytes.
Stimulation of cultured periportal and pericentral hepatocyte subpopulations
by different concentrations of growth hormone for 1Â h resulted at
100 ng mL−1 in a 1.6-fold and 4.3-fold increase of SOCS-2 mRNA,
respectively. Likewise, insulin-like growth factor-1, another physiological
target of growth hormone, was stimulated preferentially in pericentral
hepatocytes. As growth hormone receptor was found to be homogeneously
expressed in mouse liver parenchyma, our data indicate that growth
hormone signalling downstream of growth hormone receptor is more
sensitive and/or effective in pericentral than in periportal hepatocytes.
Presumably, the heterogeneous distribution of SOCS-2 may contribute
to the pericentral preference of growth hormone action via differential
feedback.},
issn = {1469-7580},
keywords = {growth hormone, hepatocytes, insulin-like growth factor-1, liver,
suppressor of cytokine signalling 2},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1469-7580.2009.01085.x}
}
@ARTICLE{Zempolich2008,
author = {Zempolich, K. and Fuhrman, C. and Milash, B. and Flinner, R. and
Greven, K. and Ryu, J. and Forbes, A. and Kerlin, K. and Nichols,
R.C. and Gaffney, D.K.},
title = {Changes in gene expression induced by chemoradiation in advanced
cervical carcinoma: A microarray study of RTOG C-0128},
journal = {Gynecologic Oncology},
year = {2008},
volume = {109},
pages = {275--279},
number = {2},
month = may,
abstract = {Purpose To evaluate gene expression patterns in patients with advanced
cervix cancer before and during chemoradiation in a multi-institutional
cooperative group setting.Methods RTOG C0128 was designed as a Phase
II trial of radiation therapy with concomitant chemotherapy and Celecoxib
at 400 mg twice daily for one year. Tumor samples were obtained for
microarray gene expression analysis before treatment and at the time
of the first implant (paired sample). RNA was extracted, linearly
amplified, and purity was assessed by gel electrophoresis. Each sample
was hybridized against a universal RNA mixture on a customized spotted
array consisting of > 10,000 genes. Gene expression pre-treatment
was compared with clinical characteristics. Changes in gene expression
following radiation were assessed within the paired samples (same
patient) and then compared across all paired samples. Data were normalized
using the AROMA software, and clustering analysis was performed using
Ward's method in Spotfire. Differences in paired samples were calculated
with Significance Analysis of Microarrays (SAM).Results From August
2001 to March 2004, 84 patients were accrued to the trial. Tissue
was obtained prior to initiation of therapy from 34 patients (40%).
FIGO stages of the patients providing tissue were IB (23%), II (57%),
and IIIA-IVA (20%). RNA quality was sufficient in 22 pre-treatment
and 14 post-treatment samples. Among pre-treatment samples, no significant
differences in gene expression were observed by FIGO stage, age,
or race. However, between comparison of histologic subtypes (adenocarcinoma,
n = 5; squamous cell carcinoma, n = 17) demonstrated 45 genes differentially
expressed with a false discovery rate of 0.018. Cluster analysis
segregated unpaired samples into 2 groups: 18/22 comprising pre-treatment
samples and 10/14 in group 2 representing post-treatment samples.
In all 13 paired samples, gene expression after chemoradiation was
significantly upregulated in 91 genes and downregulated in 251 genes
(false discovery rate of 0.0018). Genes significantly upregulated
included bax, cdk inhibitor 1, MMP2, and adhesion molecules PECAM1,
VCAM1, and ICAM2. Genes significantly downregulated included topoisomerase
II alpha, myc, H2AX, MSH2, RAD51, RAD53, PCNA, and cell cycle-regulating
molecules chk1, CDK2, cyclinB1, cyclin D3, cdc2, and cdc25.Conclusions
Microarray analysis was successfully performed in a multi-institutional
cooperative group trial. Gene expression significantly correlated
with histology, but not stage, age or race. Cluster analysis identified
two groups of gene expression profiles correlating with pre or post-treatment
acquisition of tissue. Notably, paired samples showed significant
changes in gene expression following chemoradiation, including several
downregulated radiation response genes. Further analysis comparing
gene expression to clinical outcomes, acute and late toxicities awaits
maturation of clinical data. Hopefully, this data will lead to the
development of molecularly based therapies.},
issn = {0090-8258},
keywords = {Cervical carcinoma, Gene expression, Microarray},
url = {http://www.sciencedirect.com/science/article/B6WG6-4S02PRD-2/2/1bd4243ee1e7510ffcacc3e5c80aa8c4}
}
@ARTICLE{Zenclussen2006,
author = {Zenclussen, Maria Laura and Anegon, Ignacio and Bertoja, Annarosa
Zambon and Chauveau, Christine and Vogt, Katrin and Gerlof, Katrin
and Sollwedel, André and Volk, Hans-Dieter and Ritter, Thomas and
Zenclussen, Ana Claudia},
title = {Over-expression of heme oxygenase-1 by adenoviral gene transfer improves
pregnancy outcome in a murine model of abortion},
journal = {Journal of Reproductive Immunology},
year = {2006},
volume = {69},
pages = {35--52},
number = {1},
month = feb,
abstract = {Mammalian pregnancy is a complex phenomenon allowing the maternal
immune system to support its allogeneic fetus. Physiological pathways
protecting the fetus from rejection are thought to be comparable
with those leading to allograft acceptance. Heme oxygenase (HO)-1
is known to protect locally against rejection in transplantation
models due to its anti-oxidant, anti-inflammatory and cytoprotective
functions. Based on previous data on low HO-1 levels in placenta
from mice undergoing abortion, we hypothesized that an up-regulation
of HO-1 during pregnancy would avoid fetal rejection in the murine
abortion combination CBA/J × DBA/2J, using BALB/c-mated CBA/J as
normal controls. We injected pregnant mice undergoing abortion with
1 × 105 PFU of an adenoviral vector containing HO-1 and GFP (AdHO-1/GFP),
and compared the pregnancy outcome with PBS- or 1 × 105 AdEGFP-treated
abortion-prone mice and with PBS-treated normal pregnant mice. The
abortion rate diminished significantly after adenoviral gene transfer
of AdHO-1/GFP. The systemic and local IL-4/IFN-[gamma] ratio was
augmented in AdHO-1-treated mice compared to abortion-prone mice.
Interestingly, the HO-1 treatment up-regulated the ratio IL-10/TNF-[alpha]
in spleen but not in decidual lymphocytes. HO-1-treated mice further
showed diminished apoptosis rate and increased Bag-1 mRNA levels
at the materno-fetal interface. Thus, we propose HO-1 as a key regulator
of pregnancy success. HO-1 would exert its action by locally up-regulating
the Th2/Th1 cytokine ratio and by further protecting tissues from
apoptosis.},
issn = {0165-0378},
keywords = {Gene therapy, Mouse, HO-1, Th1/Th2, Apoptosis},
url = {http://www.sciencedirect.com/science/article/B6T8W-4HX478W-2/2/01986c36a48071492feb2ea4095489fc}
}
@ARTICLE{Zeng2004,
author = {Zeng, Fanyi and Baldwin, Don A. and Schultz, Richard M.},
title = {Transcript profiling during preimplantation mouse development},
journal = {Developmental Biology},
year = {2004},
volume = {272},
pages = {483--496},
number = {2},
month = aug,
abstract = {Studies using low-resolution methods to assess gene expression during
preimplantation mouse development indicate that changes in gene expression
either precede or occur concomitantly with the major morphological
transitions, that is, conversion of the oocyte to totipotent 2-cell
blastomeres, compaction, and blastocyst formation. Using microarrays,
we characterized global changes in gene expression and used Expression
Analysis Systematic Explorer (EASE) to identify biological and molecular
processes that accompany and likely underlie these transitions. The
analysis confirmed previously described processes or events, but
more important, EASE revealed new insights. Response to DNA damage
and DNA repair genes are overrepresented in the oocyte compared to
1-cell through blastocyst stages and may reflect the oocyte's response
to selective pressures to insure genomic integrity; fertilization
results in changes in the transcript profile in the 1-cell embryo
that are far greater than previously recognized; and genome activation
during 2-cell stage may not be as global and promiscuous as previously
proposed, but rather far more selective, with genes involved in transcription
and RNA processing being preferentially expressed. These results
validate this hypothesis-generating approach by identifying genes
involved in critical biological processes that can be the subject
of a more traditional hypothesis-driven approach.},
issn = {0012-1606},
keywords = {Microarray, Gene expression, Genome activation, Maternal mRNA, Compaction,
Blastocyst},
url = {http://www.sciencedirect.com/science/article/B6WDG-4CS4K3K-2/2/ca224320151285766efa280bd32b21a8}
}
@ARTICLE{Zeng2010,
author = {Zeng, Fanning and Watson, Robert P. and Nash, Mark S.},
title = {Glial Cell-Derived Neurotrophic Factor Enhances Synaptic Communication
and 5-Hydroxytryptamine 3a Receptor Expression in Enteric Neurons},
journal = {Gastroenterology},
year = {2010},
volume = {138},
pages = {1491--1501},
number = {4},
month = apr,
abstract = {Glial cell–derived neurotrophic factor (GDNF) is essential for the
development of the enteric nervous system during embryogenesis. We
have observed the presence of Gdnf transcripts in the gastrointestinal
tract of adult mice, and its early up-regulation after inflammation.
We therefore investigated the effects of GDNF on enteric neuronal
function in vitro. Primary neuronal cultures were established from
isolated myenteric plexi, and characterized by immunostaining and
Ca2+ imaging. Gene expression of several ion channels was analyzed
by quantitative polymerase chain reaction (PCR) and the electrophysiologic
properties of the neurons were studied by patch clamp. GDNF enhanced
synaptogenesis and intercellular communication in primary myenteric
neuronal cultures. Expression profiling revealed that GDNF exposure
results in an up-regulation of Htr3a expression in the cultures and
a similar increase was observed in inflamed colonic tissue where
Gdnf expression was also increased. The increased Htr3a expression
was accompanied by a functional increase in the response of neurons
to acute challenge with 5-hydroxytryptamine (5-HT). GDNF treatment
also caused inhibition of delayed rectifying voltage-gated potassium
(Kv) currents, which correlated with the up-regulation of Htr3a and
5-HT–induced responses. Furthermore, pharmacologic blockade of
Kv channels mimicked the effect of GDNF by increasing Htr3a expression
as well as enhancing 5-HT–induced responses in the cultured myenteric
neurons. GDNF promotes synaptic communication in cultured myenteric
neurons. It also up-regulates 5-HT3a-receptor expression via modulation
of Kv channel activity. Up-regulation of Gdnf after gastrointestinal
inflammation might play an important role in the pathophysiology
of gastrointestinal diseases.},
issn = {0016-5085},
keywords = {GDNF, Enteric Neuron, 5-HT3a Receptor, Kv Channel, AP, action potential,
ENS, enteric nervous system, GDNF, Glial cell–derived neurotrophic
factor, GI, gastrointestinal, 5-HT, 5-hydroxytryptamine (serotonin),
Kv channel, voltage-gated potassium channel, PCR, polymerase chain
reaction, PMA, phorbol 12- myristate-13-acetate, TEA, tetraethylammonium},
publisher = {W.B. Saunders},
refid = {S0016-5085(09)02100-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0016508509021003?showall=true}
}
@ARTICLE{Zeng2010a,
author = {Zeng, Wei and Jiang, Nan and Nadella, Ramya and Killen, Tara L. and
Nadella, Vijayanand and Faik, Ahmed},
title = {A Glucurono(arabino)xylan Synthase Complex from Wheat Contains Members
of the GT43, GT47, and GT75 Families and Functions Cooperatively},
journal = {Plant Physiology},
year = {2010},
volume = {154},
pages = {78--97},
number = {1},
month = sep,
abstract = {Glucuronoarabinoxylans (GAXs) are the major hemicelluloses in grass
cell walls, but the proteins that synthesize them have previously
been uncharacterized. The biosynthesis of GAXs would require at least
three glycosyltransferases (GTs): xylosyltransferase (XylT), arabinosyltransferase
(AraT), and glucuronosyltransferase (GlcAT). A combination of proteomics
and transcriptomics analyses revealed three wheat (Triticum aestivum)
glycosyltransferase (TaGT) proteins from the GT43, GT47, and GT75
families as promising candidates involved in GAX synthesis in wheat,
namely TaGT43-4, TaGT47-13, and TaGT75-4. Coimmunoprecipitation experiments
using specific antibodies produced against TaGT43-4 allowed the immunopurification
of a complex containing these three GT proteins. The affinity-purified
complex also showed GAX-XylT, GAX-AraT, and GAX-GlcAT activities
that work in a cooperative manner. UDP Xyl strongly enhanced both
AraT and GlcAT activities. However, while UDP arabinopyranose stimulated
the XylT activity, it had only limited effect on GlcAT activity.
Similarly, UDP GlcUA stimulated the XylT activity but had only limited
effect on AraT activity. The [14C]GAX polymer synthesized by the
affinity-purified complex contained Xyl, Ara, and GlcUA in a ratio
of 45:12:1, respectively. When this product was digested with purified
endoxylanase III and analyzed by high-pH anion-exchange chromatography,
only two oligosaccharides were obtained, suggesting a regular structure.
One of the two oligosaccharides has six Xyls and two Aras, and the
second oligosaccharide contains Xyl, Ara, and GlcUA in a ratio of
40:8:1, respectively. Our results provide a direct link of the involvement
of TaGT43-4, TaGT47-13, and TaGT75-4 proteins (as a core complex)
in the synthesis of GAX polymer in wheat.},
url = {http://www.plantphysiol.org/cgi/content/abstract/154/1/78}
}
@ARTICLE{Zeng2007,
author = {Zeng, Wenxian and Rathi, Rahul and Pan, Hua and Dobrinski, Ina},
title = {Comparison of global gene expression between porcine testis tissue
xenografts and porcine testis in situ},
journal = {Mol. Reprod. Dev.},
year = {2007},
volume = {74},
pages = {674--679},
number = {6},
abstract = {Abstract 10.1002/mrd.20670.abs Testis tissue from immature mammalian
donor animals, grafted ectopically to immunodeficient mouse hosts,
can undergo complete spermatogenesis with the production of fertilization-competent
spermatozoa. To further characterize testis tissue xenografts as
a model for testis function in situ, the objective of this study
was to compare gene expression between porcine testis tissue xenografts
and testis tissue in situ. Pieces of testis tissue from 1-week-old
piglets were grafted onto immunodeficient male mice and a littermate
piglet was raised for comparison as control. Complete spermatogenesis
was present in the testis tissue xenografts at 8 months after transplantation
into mouse hosts and in the 8-month-old control porcine testis tissue.
Total RNA was isolated from xenografts and control tissue, and the
RNA was labeled and hybridized to the porcine genome array. By analyzing
the expression of 23,256 transcripts, we found that 71 genes were
differentially expressed with at least a fourfold difference between
xenografts and control tissue. Interestingly, none of the 56 transcripts
present on the array that were annotated in porcine testis showed
differential expression between xenografts and control testis. This
analysis indicates that global gene expression in porcine testis
xenografts appears comparable to testis tissue in situ. These findings
support the hypothesis that testis tissue xenografts can provide
a representative model to study mammalian spermatogenesis. Mol. Reprod.
Dev. 74: 674–679, 2007. © 2006 Wiley-Liss, Inc.},
issn = {1098-2795},
keywords = {testis, xenografting, microarray, pig},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mrd.20670}
}
@ARTICLE{Zeng2011,
author = {Zeng, Yajuan and Conner, Joann and Ozias-Akins, Peggy},
title = {Identification of ovule transcripts from the Apospory-Specific Genomic
Region (ASGR)-carrier chromosome},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {206},
number = {1},
abstract = {BACKGROUND:Apomixis, asexual seed production in plants, holds great
potential for agriculture as a means to fix hybrid vigor. Apospory
is a form of apomixis where the embryo develops from an unreduced
egg that is derived from a somatic nucellar cell, the aposporous
initial, via mitosis. Understanding the molecular mechanism regulating
aposporous initial specification will be a critical step toward elucidation
of apomixis and also provide insight into developmental regulation
and downstream signaling that results in apomixis. To discover candidate
transcripts for regulating aposporous initial specification in P.
squamulatum, we compared two transcriptomes derived from microdissected
ovules at the stage of aposporous initial formation between the apomictic
donor parent, P. squamulatum (accession PS26), and an apomictic derived
backcross 8 (BC8) line containing only the Apospory-Specific Genomic
Region (ASGR)-carrier chromosome from P. squamulatum. Toward this
end, two transcriptomes derived from ovules of an apomictic donor
parent and its apomictic backcross derivative at the stage of apospory
initiation, were sequenced using 454-FLX technology.RESULTS:Using
454-FLX technology, we generated 332,567 reads with an average read
length of 147 base pairs (bp) for the PS26 ovule transcriptome library
and 363,637 reads with an average read length of 142 bp for the BC8
ovule transcriptome library. A total of 33,977 contigs from the PS26
ovule transcriptome library and 26,576 contigs from the BC8 ovule
transcriptome library were assembled using the Multifunctional Inertial
Reference Assembly program. Using stringent in silico parameters,
61 transcripts were predicted to map to the ASGR-carrier chromosome,
of which 49 transcripts were verified as ASGR-carrier chromosome
specific. One of the alien expressed genes could be assigned as tightly
linked to the ASGR by screening of apomictic and sexual F1s. Only
one transcript, which did not map to the ASGR, showed expression
primarily in reproductive tissue. CONCLUSIONS:Our results suggest
that a strategy of comparative sequencing of transcriptomes between
donor parent and backcross lines containing an alien chromosome of
interest can be an efficient method of identifying transcripts derived
from an alien chromosome in a chromosome addition line.},
doi = {10.1186/1471-2164-12-206},
issn = {1471-2164},
pubmedid = {21521529},
url = {http://www.biomedcentral.com/1471-2164/12/206}
}
@ARTICLE{Zeng2008,
author = {Zeng, Zhaoyang and Velarde, Michael C. and Simmen, Frank A. and Simmen,
Rosalia C.M.},
title = {Delayed Parturition and Altered Myometrial Progesterone Receptor
Isoform A Expression in Mice Null for Kruppel-Like Factor 9},
journal = {Biol Reprod},
year = {2008},
volume = {78},
pages = {1029--1037},
number = {6},
month = jun,
abstract = {Preterm and delayed labor conditions are devastating health problems
with currently unknown etiologies. We previously showed that the
transcription factor Kruppel-like factor 9 (KLF9) influences the
expression and/or transcriptional activity of receptors for estrogen
and progesterone in endometrial cells in vivo and in vitro. Given
that estrogen and progesterone differentially regulate uterine myometrial
contractility during gestation, we hypothesized that lack of KLF9
could compromise myometrial function, leading to defects in parturition.
To test this, we used mice null for Klf9 to evaluate gestation length,
response to the progesterone receptor (PGR) antagonist RU486, expression
levels of steroid receptor proteins, nuclear receptor coactivator
and contractility-associated genes, and nuclear factor-kappaB (NF-kappaB)
DNA binding activity in myometrium near term. Klf9 knockout (KO)
mice exhibited delayed parturition by 1-2 days relative to wild-type
(WT) counterparts, in the absence of fetal genotype contribution
and differences in serum estrogen and progesterone levels. Knockout
mice near term were refractory to the abortive action of RU486, and
they displayed aberrant myometrial expression patterns of nuclear
PGR-A and NF-kappaB p65/RELA relative to WT mice. Myometrial expression
levels of nuclear estrogen receptor-alpha did not differ, whereas
those for Oxtr and Crebbp mRNAs were lower, in KO versus WT mice.
Results indicate that KLF9 contributes to the regulation of PGR-associated
components in the myometrium necessary for timely onset of parturition
in mice. The present study highlights the potential utility of Klf9
null mice to investigate the pathophysiology of parturition defects
involving PGR signaling.},
url = {http://www.biolreprod.org/cgi/content/abstract/78/6/1029}
}
@ARTICLE{Zenoni2010,
author = {Zenoni, Sara and Ferrarini, Alberto and Giacomelli, Enrico and Xumerle,
Luciano and Fasoli, Marianna and Malerba, Giovanni and Bellin, Diana
and Pezzotti, Mario and Delledonne, Massimo},
title = {Characterization of Transcriptional Complexity during Berry Development
in Vitis vinifera Using RNA-Seq},
journal = {Plant Physiology},
year = {2010},
volume = {152},
pages = {1787--1795},
number = {4},
month = apr,
abstract = {The development of massively parallel sequencing technologies enables
the sequencing of total cDNA (RNA-Seq) to derive accurate measure
of individual gene expression, differential splicing activity, and
to discover novel regions of transcription, dramatically changing
the way that the functional complexity of transcriptomes can be studied.
Here we report on the first use of RNA-Seq to gain insight into the
wide range of transcriptional responses that are associated with
berry development in Vitis vinifera Corvina'. More than 59 million
sequence reads, 36 to 44 bp in length, were generated from three
developmental stages: post setting, veraison, and ripening. The sequence
reads were aligned onto the 8.4-fold draft sequence of the Pinot
Noir 40024 genome and then analyzed to measure gene expression levels,
to detect alternative splicing events, and expressed single nucleotide
polymorphisms. We detected 17,324 genes expressed during berry development,
6,695 of which were expressed in a stage-specific manner, suggesting
differences in expression for genes in numerous functional categories
and a significant transcriptional complexity. This exhaustive overview
of gene expression dynamics demonstrates the utility of RNA-Seq for
identifying single nucleotide polymorphisms and splice variants and
for describing how plant transcriptomes change during development.},
url = {http://www.plantphysiol.org/cgi/content/abstract/152/4/1787}
}
@ARTICLE{Zernecke2009,
author = {Zernecke, Alma and Bidzhekov, Kiril and Noels, Heidi and Shagdarsuren,
Erdenechimeg and Gan, Lin and Denecke, Bernd and Hristov, Mihail
and Koppel, Thomas and Jahantigh, Maliheh Nazari and Lutgens, Esther
and Wang, Shusheng and Olson, Eric N. and Schober, Andreas and Weber,
Christian},
title = {Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent
Vascular Protection},
journal = {Sci. Signal.},
year = {2009},
volume = {2},
pages = {ra81--},
number = {100},
month = dec,
url = {http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2/100/ra81}
}
@ARTICLE{Zerwes2008,
author = {Zerwes, H.-G. and Li, J. and Kovarik, J. and Streiff, M. and Hofmann,
M. and Roth, L. and Luyten, M. and Pally, C. and Loewe, R. P. and
Wieczorek, G. and Bänteli, R. and Thoma, G. and Luckow, B.},
title = {The Chemokine Receptor Cxcr3 Is Not Essential for Acute Cardiac Allograft
Rejection in Mice and Rats},
journal = {American Journal of Transplantation},
year = {2008},
volume = {8},
pages = {1604--1613},
number = {8},
abstract = {Chemokine receptors have gained attention as potential targets for
novel therapeutic strategies. We investigated the mechanisms of allograft
rejection in chemokine receptor Cxcr3-deficient mice using a model
of acute heart allograft rejection in the strain combination BALB/c
to C57BL/6. Allograft survival was minimally prolonged in Cxcr3-deficient
mice compared to wild-type (wt) animals (8 vs. 7 days) and treatment
with a subtherapeutic dose of cyclosporine A (CsA) led to similar
survival in Cxcr3-deficient and wt recipients (13 vs. 12 days). At
rejection grafts were histologically indistinguishable. Microarray
analysis revealed that besides Cxcr3 only few genes were differentially
expressed in grafts or in spleens from transplanted or untransplanted
animals. Transcript analysis by quantitative RT-PCR of selected cytokines,
chemokines, or chemokine receptors or serum levels of selected cytokines
and chemokines showed similar levels between the two groups. Furthermore,
in a rat heart allograft transplantation model treatment with a small
molecule CXCR3 antagonist did not prolong survival despite full blockade
of Cxcr3 in vivo. In summary, Cxcr3 deficiency or pharmacologic blockade
does not diminish graft infiltration, tempo and severity of rejection.
Thus, Cxcr3 does not appear to play a pivotal role in the allograft
rejection models described here.},
issn = {1600-6143},
keywords = {Chemokine, receptors, Cxcr3, gene expression profiling, graft rejection},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1600-6143.2008.02309.x}
}
@ARTICLE{Zeschnigk2009,
author = {Zeschnigk, Michael and Martin, Marcel and Betzl, Gisela and Kalbe,
Andreas and Sirsch, Caroline and Buiting, Karin and Gross, Stephanie
and Fritzilas, Epameinondas and Frey, Bruno and Rahmann, Sven and
Horsthemke, Bernhard},
title = {Massive parallel bisulfite sequencing of CG-rich DNA fragments reveals
that methylation of many X-chromosomal CpG islands in female blood
DNA is incomplete},
journal = {Hum. Mol. Genet.},
year = {2009},
volume = {18},
pages = {1439--1448},
number = {8},
month = apr,
abstract = {Methylation of CpG islands (CGIs) plays an important role in gene
silencing. For genome-wide methylation analysis of CGIs in female
white blood cells and in sperm, we used four restriction enzymes
and a size selection step to prepare DNA libraries enriched with
CGIs. The DNA libraries were treated with sodium bisulfite and subjected
to a modified 454/Roche Genome Sequencer protocol. We obtained 163
034 and 129 620 reads from blood and sperm, respectively, with an
average read length of 133 bp. Bioinformatic analysis revealed that
12 358 (7.6%) blood library reads and 10 216 (7.9%) sperm library
reads map to 6167 and 5796 different CGIs, respectively. In blood
and sperm DNA, we identified 824 (13.7%) and 482 (8.5%) fully methylated
autosomal CGIs, respectively. Differential methylation, which is
characterized by the presence of methylated and unmethylated reads
of the same CGI, was observed in 53 and 52 autosomal CGIs in blood
and sperm DNA, respectively. Remarkably, methylation of X-chromosomal
CGIs in female blood cells was most often incomplete (25-75%). Such
incomplete methylation was mainly found on the X-chromosome, suggesting
that it is linked to X-chromosome inactivation.},
url = {http://hmg.oxfordjournals.org/cgi/content/abstract/18/8/1439}
}
@ARTICLE{Zetterblad2010,
author = {Zetterblad, Jenny and Qian, Hong and Zandi, Sasan and Månsson, Robert
and Lagergren, Anna and Hansson, Frida and Bryder, David and Paulsson,
Nils and Sigvardsson, Mikael},
title = {Genomics based analysis of interactions between developing B-lymphocytes
and stromal cells reveal complex interactions and two-way communication},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {108},
number = {1},
abstract = {BACKGROUND:The use of functional genomics has largely increased our
understanding of cell biology and promises to help the development
of systems biology needed to understand the complex order of events
that regulates cellular differentiation in vivo. One model system
clearly dependent on the integration of extra and intra cellular
signals is the development of B-lymphocytes from hematopoietic stem
cells in the bone marrow. This developmental pathway involves several
defined differentiation stages associated with specific expression
of genes including surface markers that can be used for the prospective
isolation of the progenitor cells directly from the bone marrow to
allow for ex vivo gene expression analysis. The developmental process
can be simulated in vitro making it possible to dissect information
about cell/cell communication as well as to address the relevance
of communication pathways in a rather direct manner. Thus we believe
that B-lymphocyte development represents a useful model system to
take the first steps towards systems biology investigations in the
bone marrow.RESULTS:In order to identify extra cellular signals that
promote B lymphocyte development we created a database with approximately
400 receptor ligand pairs and software matching gene expression data
from two cell populations to obtain information about possible communication
pathways. Using this database and gene expression data from NIH3T3
cells (unable to support B cell development), OP-9 cells (strongly
supportive of B cell development), pro-B and pre-B cells as well
as mature peripheral B-lineage cells, we were able to identify a
set of potential stage and stromal cell restricted communication
pathways. Functional analysis of some of these potential ways of
communication allowed us to identify BMP-4 as a potent stimulator
of B-cell development in vitro. Further, the analysis suggested that
there existed possibilities for progenitor B cells to send signals
to the stroma. The functional consequences of this were investigated
by co-culture experiments revealing that the co-incubation of stromal
cells with B cell progenitors altered both the morphology and the
gene expression pattern in the stromal cells.CONCLUSIONS:We believe
that this gene expression data analysis method allows for the identification
of functionally relevant interactions and therefore could be applied
to other data sets to unravel novel communication pathways.},
doi = {10.1186/1471-2164-11-108},
issn = {1471-2164},
pubmedid = {20152025},
url = {http://www.biomedcentral.com/1471-2164/11/108}
}
@ARTICLE{Zhai2011,
author = {Wenwu Zhai and Jacob Glanville and Markus Fuhrmann and Li Mei and
Irene Ni and Purnima D. Sundar and Thomas Van Blarcom and Yasmina
Abdiche and Kevin Lindquist and Ralf Strohner and Dilduz Telman and
Guido Cappuccilli and William J.J. Finlay and Jan Van den Brulle
and David R. Cox and Jaume Pons and Arvind Rajpal},
title = {Synthetic Antibodies Designed on Natural Sequence Landscapes},
journal = {Journal of Molecular Biology},
year = {2011},
volume = {412},
pages = {55 - 71},
number = {1},
abstract = {We present a method for synthetic antibody library generation that
combines the use of high-throughput immune repertoire analysis and
a novel synthetic technology. The library design recapitulates positional
amino acid frequencies observed in natural antibody repertoires.
V-segment diversity in four heavy (VH) and two kappa (Vκ) germlines
was introduced based on the analysis of somatically hypermutated
donor-derived repertoires. Complementarity-determining region 3 length
and amino acid designs were based on aggregate frequencies of all
VH and Vκ sequences in the data set. The designed libraries were
constructed through an adaptation of a novel gene synthesis technology
that enables precise positional control of amino acid composition
and incorporation frequencies. High-throughput pyrosequencing was
used to monitor the fidelity of construction and characterize genetic
diversity in the final 3.6 × 1010 transformants. The library
exhibited Fab expression superior to currently reported synthetic
approaches of equivalent diversity, with greater than 93% of clones
observed to successfully display both a correctly folded heavy chain
and a correctly folded light chain. Genetic diversity in the library
was high, with 95% of 7.0 × 105 clones sequenced observed
only once. The obtained library diversity explores a comparable sequence
space as the donor-derived natural repertoire and, at the same time,
is able to access novel recombined diversity due to lack of segmental
linkage. The successful isolation of low- and subnanomolar-affinity
antibodies against a diverse panel of receptors, growth factors,
enzymes, antigens from infectious reagents, and peptides confirms
the functional viability of the design strategy.},
doi = {10.1016/j.jmb.2011.07.018},
issn = {0022-2836},
keywords = {antibody repertoire},
url = {http://www.sciencedirect.com/science/article/pii/S0022283611007728}
}
@ARTICLE{Zhai2005,
author = {Zhai, Weiguo and Jeong, Hyunkyung and Cui, Libin and Krainc, Dimitri
and Tjian, Robert},
title = {In Vitro Analysis of Huntingtin-Mediated Transcriptional Repression
Reveals Multiple Transcription Factor Targets},
journal = {Cell},
year = {2005},
volume = {123},
pages = {1241--1253},
number = {7},
month = dec,
abstract = {Summary Transcriptional dysregulation has emerged as a potentially
important pathogenic mechanism in Huntington's disease, a neurodegenerative
disorder associated with polyglutamine expansion in the huntingtin
(htt) protein. Here, we report the development of a biochemically
defined in vitro transcription assay that is responsive to mutant
htt. We demonstrate that both gene-specific activator protein Sp1
and selective components of the core transcription apparatus, including
TFIID and TFIIF, are direct targets inhibited by mutant htt in a
polyglutamine-dependent manner. The RAP30 subunit of TFIIF specifically
interacts with mutant htt both in vitro and in vivo to interfere
with formation of the RAP30-RAP74 native complex. Importantly, overexpression
of RAP30 in cultured primary striatal cells protects neurons from
mutant htt-induced cellular toxicity and alleviates the transcriptional
inhibition of the dopamine D2 receptor gene by mutant htt. Our results
suggest a mutant htt-directed repression mechanism involving multiple
specific components of the basal transcription apparatus.},
issn = {0092-8674},
url = {http://www.sciencedirect.com/science/article/B6WSN-4HXBRPG-H/2/6d8f8f15f7ec8033e2066b12533da486}
}
@ARTICLE{Zhai2007,
author = {Zhai, Yali and Kuick, Rork and Nan, Bin and Ota, Ichiro and Weiss,
Stephen J. and Trimble, Cornelia L. and Fearon, Eric R. and Cho,
Kathleen R.},
title = {Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous
Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion},
journal = {Cancer Res.},
year = {2007},
volume = {67},
pages = {10163--10172},
number = {21},
month = nov,
abstract = {If left untreated, a subset of high-grade squamous intraepithelial
lesions (HSIL) of the cervix will progress to invasive squamous cell
carcinomas (SCC). To identify genes whose differential expression
is linked to cervical cancer progression, we compared gene expression
in microdissected squamous epithelial samples from 10 normal cervices,
7 HSILs, and 21 SCCs using high-density oligonucleotide microarrays.
We identified 171 distinct genes at least 1.5-fold up-regulated (and
P < 0.001) in the SCCs relative to HSILs and normal cervix samples.
Differential expression of a subset of these genes was confirmed
by quantitative reverse transcription-PCR and immunohistochemical
staining of cervical tissue samples. One of the genes up-regulated
during progression, HOXC10, was selected for functional studies aimed
at assessing its role in mediating invasive behavior of neoplastic
squamous epithelial cells. Elevated HOXC10 expression was associated
with increased invasiveness of human papillomavirus-immortalized
keratinocytes and cervical cancer-derived cell lines in both in vitro
and in vivo assays. Cervical cancer cells with high endogenous levels
of HOXC10 were less invasive after short hairpin RNA-mediated knockdown
of HOXC10 expression. Our findings support a key role for the HOXC10
homeobox protein in cervical cancer progression. Other genes with
differential expression in invasive SCC versus HSIL may contribute
to tumor progression or may be useful as markers for cancer diagnosis
or progression risk. [Cancer Res 2007;67(21):10163-72]},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/67/21/10163}
}
@ARTICLE{Zhan2011a,
author = {Zhan, Bujie and Fadista, Joao and Thomsen, Bo and Hedegaard, Jakob
and Panitz, Frank and Bendixen, Christian},
title = {Global assessment of genomic variation in cattle by genome resequencing
and high-throughput genotyping},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {557},
number = {1},
abstract = {BACKGROUND:Integration of genomic variation with phenotypic information
is an effective approach for uncovering genotype-phenotype associations.
This requires an accurate identification of the different types of
variation in individual genomes.RESULTS:We report the integration
of the whole genome sequence of a single Holstein Friesian bull with
data from single nucleotide polymorphism (SNP) and comparative genomic
hybridization (CGH) array technologies to determine a comprehensive
spectrum of genomic variation. The performance of resequencing SNP
detection was assessed by combining SNPs that were identified to
be either in identity by descent (IBD) or in copy number variation
(CNV) with results from SNP array genotyping. Coding insertions and
deletions (indels) were found to be enriched for size in multiples
of 3 and were located near the N- and C-termini of proteins. For
larger indels, a combination of split-read and read-pair approaches
proved to be complementary in finding different signatures. CNVs
were identified on the basis of the depth of sequenced reads, and
by using SNP and CGH arrays.CONCLUSIONS:Our results provide high
resolution mapping of diverse classes of genomic variation in an
individual bovine genome and demonstrate that structural variation
surpasses sequence variation as the main component of genomic variability.
Better accuracy of SNP detection was achieved with little loss of
sensitivity when algorithms that implemented mapping quality were
used. IBD regions were found to be instrumental for calculating resequencing
SNP accuracy, while SNP detection within CNVs tended to be less reliable.
CNV discovery was affected dramatically by platform resolution and
coverage biases. The combined data for this study showed that at
a moderate level of sequencing coverage, an ensemble of platforms
and tools can be applied together to maximize the accurate detection
of sequence and structural variants.},
doi = {10.1186/1471-2164-12-557},
issn = {1471-2164},
pubmedid = {22082336},
url = {http://www.biomedcentral.com/1471-2164/12/557}
}
@ARTICLE{Zhan2011b,
author = {Zhan, L. and Kerr, J. R. and Lafuente, M.-J. and Maclean, A. and
Chibalina, M. V. and Liu, B. and Burke, B. and Bevan, S. and Nasir,
J.},
title = {Altered expression and coregulation of dopamine signalling genes
in schizophrenia and bipolar disorder},
journal = {Neuropathology and Applied Neurobiology},
year = {2011},
volume = {37},
pages = {206--219},
number = {2},
abstract = {L. Zhan, J. R. Kerr, M.-J. Lafuente, A. Maclean, M. V. Chibalina,
B. Liu, B. Burke, S. Bevan and J. Nasir (2011) Neuropathology and
Applied Neurobiology37, 206–219 Altered expression and coregulation
of dopamine signalling genes in schizophrenia and bipolar disorderIntroduction:
Signalling through dopamine receptors is of critical importance in
the brain and is implicated in schizophrenia and bipolar disorder,
but its underlying molecular mechanisms remain poorly understood.
Materials and methods: Using a yeast two-hybrid approach, we previously
identified 11 novel dopamine receptor-interacting proteins. Here
we compare gene expression levels for 17 genes [including all 11
dopamine receptor interacting proteins, all 5 dopamine receptors
(DRD1–DRD5) and DARPP-32] by real-time polymerase chain reaction,
using prefrontal cortex post mortem brain samples from 33 schizophrenic,
32 bipolar disorder and 34 control subjects. Results: The expression
of C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 genes was altered in
schizophrenia and/or bipolar disorder samples relative to controls
(PÂ <Â 0.05). Hierarchical clustering analysis revealed the expression
of these five genes (C14ORF28, GNB2L1, MLLT3, DARPP-32, DRD2) is
closely correlated in patients. However, in controls, DRD2 expression
in relation to the other genes appears to be very different, suggesting
abnormal DRD2 activity is an important trigger in the pathophysiology
of schizophrenia and bipolar disorder. Conclusions: Our data suggest:
(i) C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 are important in the
pathogenesis of schizophrenia and bipolar disorder; (ii) these two
disorders share common disease-related mechanisms linked to dopamine
signalling; (iii) the expression of these genes is closely correlated;
and (iv) DRD2 provides the initial trigger in the pathogenesis of
these disorders.},
doi = {10.1111/j.1365-2990.2010.01128.x},
issn = {1365-2990},
keywords = {dopamine, dopamine receptor-interacting protein, dopamine signalling,
schizophrenia},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2990.2010.01128.x}
}
@ARTICLE{Zhan2007,
author = {Zhan, Ming and Yamaza, Haruyoshi and Sun, Yu and Sinclair, Jason
and Li, Huai and Zou, Sige},
title = {Temporal and spatial transcriptional profiles of aging in Drosophila
melanogaster},
journal = {Genome Res.},
year = {2007},
volume = {17},
pages = {1236--1243},
number = {8},
month = aug,
abstract = {Temporal and tissue-specific alterations in gene expression have profound
effects on aging of multicellular organisms. However, much remains
unknown about the patterns of molecular changes in different tissues
and how different tissues interact with each other during aging.
Previous genomic studies on invertebrate aging mostly utilized the
whole body or body parts and limited age-points, and failed to address
tissue-specific aging. Here we measured genome-wide expression profiles
of aging in Drosophila melanogaster for seven tissues representing
nervous, muscular, digestive, renal, reproductive, and storage systems
at six adult ages. In each tissue, we identified hundreds of age-related
genes exhibiting significant changes of transcript levels with age.
The age-related genes showed clear tissue-specific patterns: <10%
of them in each tissue were in common with any other tissue; <20%
of the biological processes enriched with the age-related genes were
in common between any two tissues. A significant portion of the age-related
genes were those involved in physiological functions regulated by
the corresponding tissue. Nevertheless, we identified some overlaps
of the age-related functional groups among tissues, suggesting certain
common molecular mechanisms that regulate aging in different tissues.
This study is one of the first that defined global, temporal, and
spatial changes associated with aging from multiple tissues at multiple
ages, showing that different tissues age in different patterns in
an organism. The spatial and temporal transcriptome data presented
in this study provide a basis and a valuable resource for further
genetic and genomic investigation of tissue-specific regulation of
aging.},
url = {http://genome.cshlp.org/cgi/content/abstract/17/8/1236}
}
@ARTICLE{Zhan2011,
author = {Zhan, X. and Jickling, G.C. and Tian, Y. and Stamova, B. and Xu,
H. and Ander, B.P. and Turner, R.J. and Mesias, M. and Verro, P.
and Bushnell, C. and Johnston, S.C. and Sharp, F.R.},
title = {Transient ischemic attacks characterized by RNA profiles in blood},
journal = {Neurology},
year = {2011},
volume = {77},
pages = {1718-1724},
number = {19},
abstract = {ObjectiveTransient ischemic attacks (TIA) are common. Though systemic
inflammation and thrombosis are associated with TIA, further study
may provide insight into TIA pathophysiology and possibly lead to
the development of treatments specifically targeted to TIA. We sought
to determine whether gene expression profiles in blood could better
characterize the proinflammatory and procoagulant states in TIA patients.
MethodsRNA expression in blood of TIA patients (n = 26) was compared
to vascular risk factor control subjects without symptomatic cardiovascular
disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially
expressed genes in TIA were identified by analysis of covariance
and evaluated with cross-validation and functional analyses. ResultsPatients
with TIA had different patterns of gene expression compared to controls.
There were 480 probe sets, corresponding to 449 genes, differentially
expressed between TIA and controls (false discovery rate correction
for multiple comparisons, p [≤] 0.05, absolute fold change [≥]1.2).
These genes were associated with systemic inflammation, platelet
activation, and prothrombin activation. Hierarchical cluster analysis
of the identified genes suggested the presence of 2 patterns of RNA
expression in patients with TIA. Prediction analysis identified a
set of 34 genes that discriminated TIA from controls with 100% sensitivity
and 100% specificity. ConclusionPatients with recent TIA have differences
of gene expression in blood compared to controls. The 2 gene expression
profiles associated with TIA suggests heterogeneous responses between
subjects with TIA that may provide insight into cause, risk of stroke,
and other TIA pathophysiology.},
doi = {10.1212/WNL.0b013e318236eee6},
eprint = {http://www.neurology.org/cgi/reprint/77/19/1718.pdf},
url = {http://www.neurology.org/cgi/content/abstract/77/19/1718}
}
@ARTICLE{Zhang2008,
author = {Zhang, Changqing and Barthelson, Roger A. and Lambert, Georgina M.
and Galbraith, David W.},
title = {Global Characterization of Cell-Specific Gene Expression through
Fluorescence-Activated Sorting of Nuclei},
journal = {Plant Physiology},
year = {2008},
volume = {147},
pages = {30--40},
number = {1},
month = may,
abstract = {We describe a simple and highly effective means for global identification
of genes that are expressed within specific cell types within complex
tissues. It involves transgenic expression of nuclear-targeted green
fluorescent protein in a cell-type-specific manner. The fluorescent
nuclei are then purified from homogenates by fluorescence-activated
sorting, and the RNAs employed as targets for microarray hybridization.
We demonstrate the validity of the approach through the identification
of 12 genes that are selectively expressed in phloem.},
url = {http://www.plantphysiol.org/cgi/content/abstract/147/1/30}
}
@ARTICLE{Zhang2007,
author = {Zhang, Chunsun and Xing, Da},
title = {Miniaturized PCR chips for nucleic acid amplification and analysis:
latest advances and future trends},
journal = {Nucleic Acids Res.},
year = {2007},
volume = {35},
pages = {4223--4237},
number = {13},
month = jul,
abstract = {The possibility of performing fast and small-volume nucleic acid amplification
and analysis on a single chip has attracted great interest. Devices
based on this idea, referred to as micro total analysis, microfluidic
analysis, or simply Lab on a chip' systems, have witnessed steady
advances over the last several years. Here, we summarize recent research
on chip substrates, surface treatments, PCR reaction volume and speed,
architecture, approaches to eliminating cross-contamination and control
and measurement of temperature and liquid flow. We also discuss product-detection
methods, integration of functional components, biological samples
used in PCR chips, potential applications and other practical issues
related to implementation of lab-on-a-chip technologies.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/35/13/4223}
}
@ARTICLE{Zhang2011f,
author = {Zhang, Chi and Yang, Fan and Cornelia, Reuel and Tang, Wanjin and
Swisher, Susanne and Kim, Harry},
title = {Hypoxia-inducible factor-1 is a positive regulator of Sox9 activity
in femoral head osteonecrosis},
journal = {Bone},
year = {2011},
volume = {48},
pages = {507--513},
number = {3},
month = mar,
abstract = {Legg-Calve-Perthes disease (LCPD) is a juvenile form of ischemic osteonecrosis
of the femoral head leading to femoral head deformity and premature
osteoarthritis. Femoral head osteonecrosis occurs due to blood supply
disruption which results in hypoxic injury to the femoral head. Hypoxia-inducible
factor-1 [alpha] (HIF-1[alpha]) is a master regulator of cellular
response to hypoxia. A pig model of ischemic osteonecrosis of femoral
head has been shown to have radiographic and histopathologic changes
resembling LCPD. Our preliminary studies showed that the cartilage
layer was thicker in the hypoxia group compared to the control group.
The mechanism underlying this cartilage response is not known. To
explore the hypoxia-induced downstream gene activity following the
femoral head ischemia, porcine microarray analysis of gene profiles
of chondrocytes from normal and ischemic femoral heads was performed.
In the ischemic side, the expression of Sox9, a transcription factor
required for chondrocyte differentiation, was upregulated along with
HIF-1[alpha]. Expressions of Sox9 target genes, such as type II collagen
and aggrecan, were also increased. Microarray results were confirmed
by quantitative real-time RT-PCR. In addition, immunohistochemistry
assay demonstrated that both HIF-1[alpha] and Sox9 were upregulated
in chondrocytes in ischemic femoral heads compared with normal controls.
To investigate the possible molecular mechanisms of hypoxia on Sox9
activity, we tested the effect of HIF-1[alpha] on Sox9 expression
in vitro. We made a luciferase reporter construct driven by 2 kb
Sox9 promoter. Transient transfection assay showed that HIF-1[alpha]
activated Sox9 promoter activity in a dose-dependent manner. Sox9
is known to activate type II collagen target gene expression. To
test the effect of HIF-1[alpha] on Sox9-mediated transcription, HIF-1[alpha]
was cotransfected with Sox9 in type II collagen reporter assay. Our
results demonstrated that HIF-1[alpha] enhanced Sox9-mediated transcriptional
activity. Moreover, coimmunoprecipitation assay showed that HIF-1[alpha]
associated with Sox9 directly. Taken together, these findings indicate
that HIF-1[alpha] activates Sox9 expression and enhances Sox9-mediated
transcriptional activity and that HIF-1[alpha] physically interacts
with Sox9. We speculate that HIF-1[alpha] upregulation of Sox9 activity
may have a chondroprotective role following femoral head ischemia.},
issn = {8756-3282},
keywords = {Hypoxia-inducible factor-1, Sox9, Femoral head osteonecrosis, Cartilage,
Ischemia},
url = {http://www.sciencedirect.com/science/article/pii/S8756328210017102}
}
@ARTICLE{Zhang2005,
author = {Zhang, Dekui and Ezekiel, Uthayashanker R. and Chang, Shin-Wen and
Zassenhaus, Hans Peter},
title = {Gene expression profile in dilated cardiomyopathy caused by elevated
frequencies of mitochondrial DNA mutations in the mouse heart},
journal = {Cardiovascular Pathology},
year = {2005},
volume = {14},
pages = {61--69},
number = {2},
month = mar,
abstract = {Background Elevated mitochondrial DNA (mtDNA) mutations are associated
with aging and age-related diseases, but their pathogenic potential
is unclear.Methods We performed expression profiling using an Incyte
cDNA array of a mouse model of elevated mtDNA mutations wherein random
mutations accumulate specifically in the heart. At frequencies of
about 1 mutation/10,000 base pairs, these mice show apoptosis of
cardiomyocytes and development of four-chamber dilated cardiomyopathy.Results
Significant Analysis of Microarrays (SAM) revealed that 117 genes
were altered in their expression in the transgenic (Tg) heart at
a threshold of less than one false positive, of which 34 were up-regulated
and 83 were down-regulated. Some of the changes were confirmed by
Northern and Western blots. By classification of these genes into
functional categories, we identified changes that reflected cardiac
pathology. The results indicated that cardiomyopathy caused by mtDNA
mutations was largely characterized by gene expression changes indicative
of increased fibrosis and cardiac remodeling of the extracellular
matrix. Few changes were observed, suggesting an alteration in either
mitochondrial energy production or generation of increased oxidative
stress.Conclusions Elevated frequencies of mtDNA mutations in the
mouse heart lead to gene expression changes that are associated with
remodeling of the extracellular matrix. Because cardiomyocytic death
by apoptosis is also a feature of the dilated cardiomyopathy evident
in these mice, extracellular remodeling may be a response to apoptotic
signaling originating from the mitochondria with mtDNA mutations.},
issn = {1054-8807},
keywords = {Mitochondria, Mutations, Dilated cardiomyopathy, Mice},
url = {http://www.sciencedirect.com/science/article/B6T13-4FR444C-5/2/7bdc1ec8f23698e0bd7c62b60676bf31}
}
@ARTICLE{Zhang2004,
author = {Zhang, Dong-Yi and Sabla, Gregg and Shivakumar, Pranavkumar and Tiao,
Greg and Sokol, Ronald J. and Mack, Cara and Shneider, Benjamin L.
and Aronow, Bruce and Bezerra, Jorge A.},
title = {Coordinate expression of regulatory genes differentiates embryonic
and perinatal forms of biliary atresia},
journal = {Hepatology},
year = {2004},
volume = {39},
pages = {954--962},
number = {4},
abstract = {Abstract 10.1002/hep.20135.abs The molecular basis for the embryonic
and perinatal clinical forms of biliary atresia is largely undefined.
In this study, we aimed to: 1) determine if the clinical forms can
be differentiated at the transcriptional level, and 2) search for
molecular mechanisms underlying phenotypic differences. To this end,
we generated biotinylated cRNA probes from livers of age-matched
infants with the embryonic (n = 5) and perinatal (n = 6) forms of
biliary atresia at the time of diagnosis and hybridized them against
the Affymetrix human HG-U133 A and B microarrays containing 44,760
gene products. Data filtering and two-way cluster analysis of the
gene expression platform identified 230 genes with an expression
profile that is highly distinctive of the clinical phenotypes. Functionally,
the profile did not reveal a higher-order function for a specific
cell type; instead, it uncovered a coordinated expression of regulatory
genes. These regulatory genes were predominantly represented in the
embryonic form (45% of genes), with a unique pattern of expression
of genes involved in chromatin integrity/function (Smarca-1, Rybp,
and Hdac3) and the uniform overexpression of five imprinted genes
(Igf2, Peg3, Peg10, Meg3, and IPW), implying a failure to downregulate
embryonic gene programs. In conclusion, embryonic and perinatal forms
of biliary atresia are distinguished by gene expression profiling.
The coordinate expression of regulators of chromatin structure/function
and of imprinted genes provides evidence for a transcriptional basis
for the pathogenesis of the embryonic form of biliary atresia. Further
studies exploring these biological processes are required to determine
the significance of these findings. Supplementary material for this
article can be found at http://genet.cchmc.org. (HEPATOLOGY 2004;39:954–962.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.20135}
}
@ARTICLE{Zhang2006,
author = {Zhang, Fuquan and Hopwood, Paul and Abrams, Charles C. and Downing,
Alison and Murray, Frazer and Talbot, Richard and Archibald, Alan
and Lowden, Stewart and Dixon, Linda K.},
title = {Macrophage Transcriptional Responses following In Vitro Infection
with a Highly Virulent African Swine Fever Virus Isolate},
journal = {J. Virol.},
year = {2006},
volume = {80},
pages = {10514--10521},
number = {21},
month = nov,
abstract = {We used a porcine microarray containing 2,880 cDNAs to investigate
the response of macrophages to infection by a virulent African swine
fever virus (ASFV) isolate, Malawi LIL20/1. One hundred twenty-five
targets were found to be significantly altered at either or both
4 h and 16 h postinfection compared with targets after mock infection.
These targets were assigned into three groups according to their
temporal expression profiles. Eighty-six targets showed increased
expression levels at 4 h postinfection but returned to expression
levels similar to those in mock-infected cells at 16 h postinfection.
These encoded several proinflammatory cytokines and chemokines, surface
proteins, and proteins involved in cell signaling and trafficking
pathways. Thirty-four targets showed increased expression levels
at 16 h postinfection compared to levels at 4 h postinfection and
in mock-infected cells. One host gene showed increased expression
levels at both 4 and 16 h postinfection compared to levels in mock-infected
cells. The microarray results were validated for 12 selected genes
by quantitative real-time PCR. Levels of protein expression and secretion
were measured for two proinflammatory cytokines, interleukin 1{beta}
and tumor necrosis factor alpha, during a time course of infection
with either the virulent Malawi LIL20/1 isolate or the OUR T88/3
nonpathogenic isolate. The results revealed differences between these
two ASFV isolates in the amounts of these cytokines secreted from
infected cells.},
url = {http://jvi.asm.org/cgi/content/abstract/80/21/10514}
}
@ARTICLE{Zhang2008a,
author = {Zhang, Fan and Sha, Jian and Wood, Thomas G. and Galindo, Cristi
L. and Garner, Harold R. and Burkart, Mark F. and Suarez, Giovanni
and Sierra, Johanna C. and Agar, Stacy L. and Peterson, Johnny W.
and Chopra, Ashok K.},
title = {Alteration in the activation state of new inflammation-associated
targets by phospholipase A2-activating protein (PLAA)},
journal = {Cellular Signalling},
year = {2008},
volume = {20},
pages = {844--861},
number = {5},
month = may,
abstract = {Phospholipase A2 (PLA2)-activating protein (PLAA) is a novel signaling
molecule that regulates the production of prostaglandins (PGE2) and
tumor necrosis factor (TNF)-[alpha]. To characterize the function
of native PLAA in situ, we generated HeLa (Tet-off) cells overexpressing
plaa (plaahigh) and control (plaalow) cells, with the plaa gene in
opposite orientation in the latter construct. The plaahigh cells
produced significantly more PGE2 and interleukin (IL)-6 compared
to plaalow cells in response to TNF-[alpha]. There was an increased
activation and/or expression of cytosolic PLA2, cyclooxgenase-2,
and NF-[kappa]B after induction of plaahigh cells with TNF-[alpha]
compared to the respective plaalow cells. Microarray analysis of
plaahigh cells followed by functional assays revealed increased production
of proinflammatory cytokine IL-32 and a decrease in the production
of annexin A4 and clusterin compared to plaalow cells. We demonstrated
the role of annexin A4 as an inhibitor of PLA2 and showed that addition
of exogeneous clusterin limited the production of PGE2 from plaahigh
cells. To understand regulation of plaa gene expression, we used
a luciferase reporter system in HeLa cells and identified one stimulatory
element, with Sp1 binding sites, and one inhibitory element, in exon
1 of the plaa gene. By using decoy DNA oligonucleotides to Sp1 and
competitive binding assays, we showed that Sp1 maintains basal expression
of the plaa gene and binds to the above-mentioned stimulatory element.
We demonstrated for the first time that the induction of native PLAA
by TNF-[alpha] can perpetuate inflammation by enhancing activation
of PLA2 and NF-[kappa]B.},
issn = {0898-6568},
keywords = {Phospholipase A2-activating protein, PGE2, NF-[kappa]B, Annexin A4,
IL-32, Clusterin},
url = {http://www.sciencedirect.com/science/article/B6T2M-4RM1KW2-1/2/5b73a830ccea84e141ddf252c5a2a065}
}
@ARTICLE{Zhang2009,
author = {Zhang, Fanglin and Sriram, Subramaniam},
title = {Identification and characterization of the interferon-β-mediated
p53 signal pathway in human peripheral blood mononuclear cells},
journal = {Immunology},
year = {2009},
volume = {128},
pages = {e905--e918},
number = {1pt2},
abstract = {Summary The relationship between the p53 signal pathway and the response
of human peripheral blood mononuclear cells (PBMC) to interferon
(IFN)-β has hitherto not been examined. Using an oligonucleotide
microarray, we found differential expression of at least 70 genes
involved in the p53 signal pathway, including p53, which regulate
cell proliferation and cell death following stimulation with IFN-β.
We verified our observations on a limited set of p53-regulated genes
at the transcriptional and translational levels. We also examined
the consequences of the activation of the p53 signal pathway by IFN-β
in PBMC. When cultured in the presence of T-cell mitogens, IFN-β
restricted the entry of lymphocytes from the G0/G1 phase to the S
phase and reduced the number of cells in the G2 phase. The addition
of IFN-β alone did not increase apoptosis. However, in the presence
of actinomycin D, a DNA-damaging agent, addition of IFN-β enhanced
the susceptibility of PBMC to apoptosis. These observations suggest
that, in spite of the activation of a number of mutually overlapping
pathways mediating cell death, cell cycle arrest was the most evident
consequence of IFN-β signalling in PBMC.},
issn = {1365-2567},
keywords = {apoptosis, interferon-β, cell cycle arrest, lymphocytes, p53},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2567.2009.03104.x}
}
@ARTICLE{Zhang2011a,
author = {Zhang, G. and Rudney, J.D.},
title = {Streptococcus cristatus attenuates Fusobacterium nucleatum-induced
cytokine expression by influencing pathways converging on nuclear
factor-κB},
journal = {Molecular Oral Microbiology},
year = {2011},
volume = {26},
pages = {150--163},
number = {2},
abstract = {Summary We previously reported that Streptococcus cristatus, an oral
commensal, was able to downregulate the interleukin-8 (IL-8) response
to Fusobacterium nucleatum, a putative oral pathogen in oral epithelial
cells. The aim of this study was to extend the understanding of how
S. cristatus regulates cytokine expression in oral epithelial cells
on a broad basis, and investigate whether the modulation of a Toll-like
receptor (TLR) pathway was involved in this process. KB and TERT-2
cells were co-cultured with F. nucleatum and S. cristatus, either
alone or in combination. Total RNA was extracted and pathway-specific
focused microarrays were used to profile the transcriptional responses
of various cytokine genes and those related to TLR-mediated signal
transduction. Reverse transcription–polymerase chain reactions
(RT-PCR) and protein assays were performed to confirm the microarray
results for selected genes. We found that exposure to either S. cristatus
or F. nucleatum alone led to distinct changes in cytokine expression
patterns. Fusobacterium nucleatum induced a greater number of gene
expression changes than S. cristatus (15% vs. 4%, respectively).
The presence of S. cristatus with F. nucleatum attenuated the expression
of a number of inflammatory cytokines, and upregulated several anti-inflammatory
mediators. The RT-PCR confirmed the messenger RNA attenuation of
IL-1α, tumor necrosis factor-α and IL-6 by S. cristatus. Profiling
of TLR-signaling-related genes revealed that S. cristatus most significantly
impacted the downstream pathways, especially nuclear factor-κB,
rather than altering TLRs and their adaptors and interacting proteins.
Our data suggest that S. cristatus may attenuate the epithelial
proinflammatory cytokine response to F. nucleatum by influencing
pathways converging on nuclear factor-κB.},
doi = {10.1111/j.2041-1014.2010.00600.x},
issn = {2041-1014},
keywords = {cytokines, epithelial cells, Fusobacterium nucleatum, inflammatory
response, nuclear factor-κB, Streptococcus cristatus},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.2041-1014.2010.00600.x}
}
@ARTICLE{Zhang2009a,
author = {Zhang, Huayan and Garber, Samuel and Cui, Zheng and Foley, Joseph
and Mohan, Gopi and Jobanputra, Minesh and Kaplan, Feige and Sweezey,
Neil and Gonzales, Linda and Savani, Rashmin},
title = {The angiogenic factor midkine is regulated by dexamethasone and retinoic
acid during alveolarization and in alveolar epithelial cells},
journal = {Respiratory Research},
year = {2009},
volume = {10},
pages = {77},
number = {1},
abstract = {BACKGROUND:A precise balance exists between the actions of endogenous
glucocorticoids (GC) and retinoids to promote normal lung development,
in particular during alveolarization. The mechanisms controlling
this balance are largely unknown, but recent evidence suggests that
midkine (MK), a retinoic acid-regulated, pro-angiogenic growth factor,
may function as a critical regulator. The purpose of this study was
to examine regulation of MK by GC and RA during postnatal alveolar
formation in rats.METHODS:Newborn rats were treated with dexamethasone
(DEX) and/or all-trans-retinoic acid (RA) during the first two weeks
of life. Lung morphology was assessed by light microscopy and radial
alveolar counts. MK mRNA and protein expression in response to different
treatment were determined by Northern and Western blots. In addition,
MK protein expression in cultured human alveolar type 2-like cells
treated with DEX and RA was also determined.RESULTS:Lung histology
confirmed that DEX treatment inhibited and RA treatment stimulated
alveolar formation, whereas concurrent administration of RA with
DEX prevented the DEX effects. During normal development, MK expression
was maximal during the period of alveolarization from postnatal day
5 (PN5) to PN15. DEX treatment of rat pups decreased, and RA treatment
increased lung MK expression, whereas concurrent DEX+RA treatment
prevented the DEX-induced decrease in MK expression. Using human
alveolar type 2 (AT2)-like cells differentiated in culture, we confirmed
that DEX and cAMP decreased, and RA increased MK expression.CONCLUSION:We
conclude that MK is expressed by AT2 cells, and is differentially
regulated by corticosteroid and retinoid treatment in a manner consistent
with hormonal effects on alveolarization during postnatal lung development.},
doi = {10.1186/1465-9921-10-77},
issn = {1465-9921},
pubmedid = {19698107},
url = {http://respiratory-research.com/content/10/1/77}
}
@ARTICLE{Zhang2010f,
author = {Zhang, Hongjie and Zhang, Jia and Pope, Christine F. and Crawford,
Laura A. and Vasavada, Rupangi C. and Jagasia, Shubhada M. and Gannon,
Maureen},
title = {Gestational Diabetes Mellitus Resulting From Impaired {beta}-Cell
Compensation in the Absence of FoxM1, a Novel Downstream Effector
of Placental Lactogen},
journal = {Diabetes},
year = {2010},
volume = {59},
pages = {143--152},
number = {1},
month = jan,
abstract = {OBJECTIVEThe objectives of the study were to determine whether the
cell cycle transcription factor, FoxM1, is required for glucose homeostasis
and {beta}-cell mass expansion in maternal islets during pregnancy
and whether FoxM1 is essential for placental lactogen (PL)-induced
{beta}-cell proliferation. RESEARCH DESIGN AND METHODS{beta}-Cell
mass, {beta}-cell proliferation, and glucose homeostasis were assessed
in virgin, pregnant, and postpartum mice with a pancreas-wide Foxm1
deletion (FoxM1{Delta}panc). Wild-type islets were cultured with
or without PL and examined for Foxm1 induction. Transgenic mice overexpressing
PL in {beta}-cells were bred with FoxM1{Delta}panc mice, and {beta}-cell
proliferation was examined. RESULTSFoxm1 was upregulated in maternal
islets during pregnancy. In contrast to controls, {beta}-cell proliferation
did not increase in pregnant FoxM1{Delta}panc females. Mutant islets
showed increased Menin and nuclear p27. FoxM1{Delta}panc females
developed gestational diabetes mellitus as pregnancy progressed.
After parturition, euglycemia was restored in FoxM1{Delta}panc females,
but islet size was significantly reduced. Strikingly, {beta}-cell
mass was normal in postpartum FoxM1{Delta}panc pancreata due to a
combination of increased {beta}-cell size and islet neogenesis. Evidence
for neogenesis included increased number of endocrine clusters, increased
proportion of smaller islets, and increased neurogenin 3 or insulin
expression in cells adjacent to ducts. PL induced Foxm1 expression
in cultured islets, and FoxM1 was essential for PL-mediated increases
in {beta}-cell proliferation in vivo. CONCLUSIONSFoxM1 is essential
for {beta}-cell compensation during pregnancy. In the absence of
increased {beta}-cell proliferation, neogenesis is induced in postpartum
FoxM1{Delta}panc pancreata. Our results suggest that FoxM1 functions
downstream of PL to mediate its effects on {beta}-cell proliferation.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/59/1/143}
}
@ARTICLE{Zhang2009b,
author = {Zhang, Jiaqin and Banerjee, Anirban and Biswas, Indranil},
title = {Transcription of clpP Is Enhanced by a Unique Tandem Repeat Sequence
in Streptococcus mutans},
journal = {J. Bacteriol.},
year = {2009},
volume = {191},
pages = {1056--1065},
number = {3},
month = feb,
abstract = {Streptococcus mutans, the primary causative agent of human dental
caries, contains a single copy of the gene encoding ClpP, the chief
intracellular protease responsible for tolerance to various environmental
stresses. To better understand the role of ClpP in stress response,
we investigated the regulation of clpP expression in S. mutans. Using
semiquantitative reverse transcription-PCR analysis, we observed
that, under nonstressed conditions, clpP expression is somewhat constant
throughout the growth phases, although it gradually decreases as
cells enter the late stationary phase. The half-life of the clpP
transcript was found to be less than 1 minute. Sequence analysis
of the clpP locus reveals the presence of a 50-bp tandem repeat sequence
located immediately upstream of the clpP promoter (PclpP). PCR and
DNA sequence analyses suggest that the number of tandem repeat units
can vary from as few as two to as many as nine, depending on the
particular S. mutans isolate. Further analysis, using a transcriptional
reporter fusion consisting of PclpP fused to a promoterless gusA
gene, indicates that the presence of the repeat sequence region within
PclpP results in an approximately fivefold increase in expression
from PclpP compared to the repeat-free transcriptional reporter fusion.
CtsR, a transcriptional repressor that negatively regulates clpP
expression, has no effect on this repeat-mediated induction of clpP
transcription. Furthermore, the repeat sequence is not necessary
for the induction of clpP under stress conditions. Database searches
indicate that the region containing the tandem repeats is absent
in the clpP loci in other bacteria, including other closely related
Streptococcus spp., suggesting that the repeat sequences are specific
for the induction of clpP expression in S. mutans. We speculate that
a host-specific transcriptional activator might be involved in the
upregulation of clpP expression in S. mutans.},
url = {http://jb.asm.org/cgi/content/abstract/191/3/1056}
}
@ARTICLE{Zhang2011e,
author = {Jianhu Zhang and Vishnu Chintalgattu and Tiffany Shih and Di Ai and
Ying Xia and Aarif Y. Khakoo},
title = {MicroRNA-9 is an activation-induced regulator of PDGFR-beta expression
in cardiomyocytes},
journal = {Journal of Molecular and Cellular Cardiology},
year = {2011},
volume = {51},
pages = {337 - 346},
number = {3},
abstract = {The platelet derived growth factor receptor (PDGFR) is an important
target for novel anti-cancer therapeutics, but agents targeting PDGFR
have been associated with cardiotoxicity. Cardiomyocyte PDGFR-β
signaling in pressure-overloaded hearts induces compensatory angiogenesis
via a paracrine-signaling cascade. Tight regulation of receptor tyrosine
kinases in response to ligand stimulation is a critical part of any
such cascade. The objective of the present study was to characterize
the early and late regulation of PDGFR-β following ligand stimulation
and define a potential role for microRNAs (miRNAs) predicted to interact
with the 3′UTR of PDGFR-β in feedback regulation. Using two in-vitro
model systems (U87 glioblastoma cells and neonatal cardiomyocytes),
we observed that in response to stimulation with PDGF-BB, levels
of PDGFR-β declined beginning at one hour, persisting for 48 h.
PDGFR-β mRNA levels declined beginning at 6 h after receptor
activation. Early, but not late activation-induced receptor downregulation
was proteasome dependent. Levels of miRNA-9 (miR-9) were significantly
increased in U87 cells and cardiomyocytes beginning 6 h after
addition of ligand. In response to pressure overload, miR-9 levels
were significantly reduced in the hearts of cardiac-specific PDGFR-β
knockout mice. Luciferase reporter assays demonstrate that miR-9
directly interacts with its predicted seed in the 3′UTR of PDGFR-β.
Increasing miR-9 levels reduces levels of PDGFR-β, resulting in
a reduction in the paracrine angiogenic capacity of cardiomyocytes,
consistent with the established function of cardiomyocyte PDGFR-β.
Importantly, increase of anti-miR-9 in cardiomyocytes attenuates
ligand-induced PDGFR-β downregulation. In conclusion, we have identified
miR-9 as an activation-induced regulator of PDGFR-β expression in
cardiomyocytes that is part of a negative feedback loop which serves
to modulate PDGFR-β expression upon ligand-stimulation through direct
interaction with the 3′UTR of PDFGR-β. This article is part of
a Special Issue entitled ‘Possible Editorial’.},
doi = {10.1016/j.yjmcc.2011.05.019},
issn = {0022-2828},
keywords = {Platelet derived growth factor},
url = {http://www.sciencedirect.com/science/article/pii/S0022282811002203}
}
@ARTICLE{Zhang2007a,
author = {Zhang, Jun and Gassmann, Marcus and Chen, Xuming and Burger, Christian
and Rong, Lixia and Ying, Qicong and Chu, Benjamin},
title = {Characterization of a Reversible Thermoresponsive Gel and Its Application
to Oligonucleotide Separation},
journal = {Macromolecules},
year = {2007},
volume = {40},
pages = {5537-5544},
number = {15},
doi = {10.1021/ma070554n},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma070554n},
url = {http://pubs.acs.org/doi/abs/10.1021/ma070554n}
}
@ARTICLE{Zhang2006a,
author = {Zhang, J and Gassmann, M and He, W and Wan, F and Chu, B},
title = {Reversible thermo-responsive sieving matrix for oligonucleotide separation.},
journal = {Lab Chip},
year = {2006},
volume = {6},
pages = {526-33--},
number = {4},
month = apr,
abstract = {A reversible thermo-responsive gel system, consisting of Pluronic
copolymer mixture of F87 and F127, has been used to successfully
carry out the separation of oligonucleotides, for the first time,
by microchip-based capillary electrophoresis. Pluronic triblock copolymers
F87 (E(61)P(40)E(61)) and F127 (E(99)P(69)E(99)), with E, P, and
subscript denoting oxyethylene, oxypropylene, and segment length
respectively, have a unique temperature dependent viscosity-adjustable
property and a dynamic coating ability in aqueous solution, including
1 x TBE buffer. The mixture solution has a reversible thermo-responsive
property and its sol-gel transition temperature can be adjusted ranging
from about 17 degrees C to 38 degrees C by varying the relative weight
ratio of F87 and F127 at an optimized concentration of approximately
30% (w/v) for oligonucleotide separations. Oligonucleotide sizing
markers ranging from 8 to 32 base could be successfully separated
in a 1.5 cm long separation channel by the mixture solution in its
gel-like state. A 30% (w/v) with a F87/F127 weight ratio of 1 ratio
2 which has a "sol-gel" transition point of about 26 degrees C shows
the best sieving ability. The sieving ability of the mixture solution
was further confirmed in an Agilent Bioanalyzer 2100 system. Fast
separation of oligonucleotides has been achieved within 40 s with
one base resolution.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16572215}
}
@ARTICLE{Zhang2006b,
author = {Zhang, Jun and He, Weidong and Liang, Dehai and Fang, Dufei and Chu,
Benjamin and Gassmann, Marcus},
title = {Designing polymer matrix for microchip-based double-stranded DNA
capillary electrophoresis},
journal = {Journal of Chromatography A},
year = {2006},
volume = {1117},
pages = {219--227},
number = {2},
month = jun,
abstract = {Polyacrylamide (PAM) was used as a model polymer to build up an empirical
model that relates polymer molecular weight, polymer concentration
and solution viscosity. The desired random copolymers of acrylamide
(AM) and N,N-dimethylacrylamide (DMA) used as DNA separation media
for different specifications were synthesized under the guidance
of the empirical model. The separation performances of rationally
designed copolymers were tested in a 1.2 cm long separation channel,
simulating microchip-based capillary electrophoresis. pBR322/HaeIII
digest was successfully separated with good separation resolution
and fast speed. Validation of the sieving ability of our polymers
was performed in the Agilent 2100 Bioanalyzer. The results of the
10 bp (base pair) DNA ladder separation demonstrate the potential
of our approach for the sieving matrix in microchip-based electrophoresis.},
issn = {0021-9673},
keywords = {Double-stranded DNA (dsDNA) fragments, Microchip-based capillary electrophoresis,
Fast DNA separations, Random copolymers, DNA labchip},
url = {http://www.sciencedirect.com/science/article/B6TG8-4JS20CN-2/2/37418157d38a432332b5d4fbdade0288}
}
@ARTICLE{Zhang2004a,
author = {Zhang, Jianhua and Moseley, Amy and Jegga, Anil G. and Gupta, Ashima
and Witte, David P. and Sartor, Maureen and Medvedovic, Mario and
Williams, Sarah S. and Ley-Ebert, Cathy and Coolen, Lique M. and
Egnaczyk, Gregory and Genter, Mary Beth and Lehman, Michael and Lingrel,
Jerry and Maggio, John and Parysek, Linda and Walsh, Ryan and Xu,
Ming and Aronow, Bruce J.},
title = {Neural system-enriched gene expression: relationship to biological
pathways and neurological diseases},
journal = {Physiol Genomics},
year = {2004},
volume = {18},
pages = {167--183},
number = {2},
month = jul,
abstract = {To understand the commitment of the genome to nervous system differentiation
and function, we sought to compare nervous system gene expression
to that of a wide variety of other tissues by gene expression database
construction and mining. Gene expression profiles of 10 different
adult nervous tissues were compared with that of 72 other tissues.
Using ANOVA, we identified 1,361 genes whose expression was higher
in the nervous system than other organs and, separately, 600 genes
whose expression was at least threefold higher in one or more regions
of the nervous system compared with their median expression across
all organs. Of the 600 genes, 381 overlapped with the 1,361-gene
list. Limited in situ gene expression analysis confirmed that identified
genes did represent nervous system-enriched gene expression, and
we therefore sought to evaluate the validity and significance of
these top-ranked nervous system genes using known gene literature
and gene ontology categorization criteria. Diverse functional categories
were present in the 381 genes, including genes involved in intracellular
signaling, cytoskeleton structure and function, enzymes, RNA metabolism
and transcription, membrane proteins, as well as cell differentiation,
death, proliferation, and division. We searched existing public sites
and identified 110 known genes related to mental retardation, neurological
disease, and neurodegeneration. Twenty-one of the 381 genes were
within the 110-gene list, compared with a random expectation of 5.
This suggests that the 381 genes provide a candidate set for further
analyses in neurological and psychiatric disease studies and that
as a field, we are as yet, far from a large-scale understanding of
the genes that are critical for nervous system structure and function.
Together, our data indicate the power of profiling an individual
biologic system in a multisystem context to gain insight into the
genomic basis of its structure and function.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/18/2/167}
}
@ARTICLE{Zhang2008b,
author = {Zhang, Jing and Oh, Kook-Hwan and Xu, Hui and Margetts, Peter J.},
title = {Vascular endothelial growth factor expression in peritoneal mesothelial
cells undergoing transdifferentiation},
journal = {Perit. Dial. Int.},
year = {2008},
volume = {28},
pages = {497--504},
number = {5},
month = sep,
abstract = {{diamondsuit} Objective: To analyze gene expression of localized peritoneal
tissue structures in a rodent model of peritoneal fibrosis. {diamondsuit}
Methods: Female Sprague Dawley rats were treated with an intraperitoneal
injection of an adenovirus expressing active transforming growth
factor-beta or control adenovirus. Four and 7 days after infection,
animals were sacrificed and frozen sections of parietal peritoneum
were subjected to immunofluorescence-aided laser capture microdissection
in order to isolate vascular, mesothelial, and submesothelial structures.
RNA was extracted from microdissected tissue and gene expression
was analyzed by quantitative reverse-transcript polymerase chain
reaction. We analyzed genes involved in angiogenesis, epithelial-to-mesenchymal
transdifferentiation, and fibrosis. Vascular endothelial growth factor
and alpha-smooth muscle actin expression was analyzed with immunohistochemistry
of formalin-fixed tissue. {diamondsuit} Results: Transforming growth
factor-{beta}1 induced expression of Snail and alpha-smooth muscle
actin genes in the peritoneal mesothelium. This same cell population
also demonstrated increased gene expression of vascular endothelial
growth factor. The distribution of this growth factor was confirmed
by immunohistochemistry. The fibrogenic growth factor, connective
tissue growth factor, was also strongly induced in the peritoneal
mesothelium. {diamondsuit} Conclusions: Using immunofluorescence-aided
laser capture microdissection, we were able to study gene expression
in subcompartments of the peritoneal tissue. We demonstrated that
mesothelial cells exhibiting mesenchymal transdifferentiation are
associated with increased expression of genes associated with fibrosis
and angiogenesis.},
url = {http://www.pdiconnect.com/cgi/content/abstract/28/5/497}
}
@ARTICLE{Zhang2010a,
author = {Zhang, Jie and Olsson, Lisbeth and Nielsen, Jens},
title = {The b-subunits of the Snf1 kinase in Saccharomyces cerevisiae, Gal83
and Sip2, but not Sip1, are redundant in glucose derepression and
regulation of sterol biosynthesis},
journal = {Molecular Microbiology},
year = {2010},
volume = {77},
pages = {371--383},
number = {2},
abstract = {Summary The conserved Snf1/AMP-activated protein kinase family is
one of the central components in the nutrient sensing and regulation
of the carbon metabolism in eukaryotes. It is also involved in several
other processes such as stress resistance, invasive growth and ageing.
Snf1 kinase is composed of a catalytic α-subunit Snf1, a regulatory
γ-subunit Snf4 and one of three possible β-subunits, Sip1, Sip2
or Gal83. We used a systematic approach to study the role of the
three β-subunits by analysing all seven possible combinations of
β-subunit deletions together with the reference strain. Previous
studies showed that the three β-subunits are redundant for growth
on alternative carbon sources. Here we report that the mutant strain
with only SIP1 expressed (sip2Δgal83Δ) could utilize acetate, but
neither ethanol nor glycerol, as alternative carbon source. We also
showed that Gal83 is the most important isoform not only for the
growth on non-fermentable carbon sources, but also for regulation
of ergosterol biosynthetic genes, under glucose-limited condition.
Furthermore, we found that Sip2, but not Sip1, can take over when
Gal83 is deleted, but to a lesser extent. However, Sip1 may be sufficient
for some other processes such as regulation of the nitrogen metabolism
and meiosis.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2010.07209.x}
}
@ARTICLE{Zhang2009c,
author = {Zhang, Jiawei and Rubio, Valentina and Lieberman, Michael W. and
Shi, Zheng-Zheng},
title = {OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional
mechanisms},
journal = {PNAS},
year = {2009},
volume = {106},
pages = {15356--15361},
number = {36},
month = sep,
abstract = {Oxidative stress has been implicated in diverse disease states and
aging. To date, induction of cellular responses to combat oxidative
stress has been characterized largely at the transcriptional level,
with emphasis on Nrf2-mediated activation of antioxidant response
elements. In this study, we demonstrate that OLA1, a novel Obg-like
ATPase, functions as a negative regulator of the cellular antioxidant
response independent of transcriptional processes. Knockdown of OLA1
in human cells elicited an increased resistance to oxidizing agents
including tert-butyl hydroperoxide (tBH) and diamide without affecting
cell proliferation, baseline apoptosis, or sensitivity to other cytotoxic
agents that target the mitochondria, cytoskeleton, or DNA. Conversely,
overexpression of OLA1 increased cellular sensitivity to tBH and
diamide. When challenged with oxidants, OLA1-knockdown cells had
decreased production of intracellular reactive oxygen species and
exhibited less depletion of reduced glutathione. Surprisingly, knockdown
of OLA1 caused only minimal genomic response; no changes were found
in the mRNA levels of genes encoding antioxidant enzymes, enzymes
that produce antioxidants (including glutathione), or other genes
known to respond to Nrf2. Moreover, when de novo protein synthesis
was blocked by cycloheximide in OLA1-knockdown cells, they continued
to demonstrate increased resistance to both tBH and diamide. These
data demonstrate that OLA1 suppresses the antioxidant response through
nontranscriptional mechanisms. The beneficial effects observed upon
OLA1-knockdown suggest that this regulatory ATPase is a potential
novel target for antioxidative therapy.},
url = {http://www.pnas.org/cgi/content/abstract/106/36/15356}
}
@ARTICLE{Zhang2009d,
author = {Zhang, Junlong and Zhang, Fang and Didelot, Xavier and Bruce, Kimberley
and Cagampang, Felino and Vatish, Manu and Hanson, Mark and Lehnert,
Hendrik and Ceriello, Antonio and Byrne, Christopher},
title = {Maternal high fat diet during pregnancy and lactation alters hepatic
expression of insulin like growth factor-2 and key microRNAs in the
adult offspring},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {478},
number = {1},
abstract = {BACKGROUND:miRNAs play important roles in the regulation of gene functions.
Maternal dietary modifications during pregnancy and gestation have
long-term effects on the offspring, but it is not known whether a
maternal high fat (HF) diet during pregnancy and lactation alters
expression of key miRNAs in the offspring.RESULTS:We studied the
effects of maternal HF diet on the adult offspring by feeding mice
with either a HF or a chow diet prior to conception, during pregnancy
and lactation, and all offspring were weaned onto the same chow diet
until adulthood. Maternal HF fed offspring had markedly increased
hepatic mRNA levels of peroxisome proliferator activated receptor-alpha
(ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well
as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation
of ppar-alpha and cpt-1a expression in the wild type but not in Igf2
knock out mice. Furthermore, hepatic expression of let-7c was also
reduced in maternal HF fed offspring. Among 579 miRNAs measured with
microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced
expression of miR-709 (a highly expressed miRNA), miR-122, miR-192,
miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483*
(reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG
binding protein 2 was the common predicted target for miR-709, miR-let7s,
miR-122, miR-194 and miR-26a using our own purpose-built computer
program.CONCLUSION:Maternal HF feeding during pregnancy and lactation
induced co-ordinated and long-lasting changes in expression of Igf2,
fat metabolic genes and several important miRNAs in the offspring.},
doi = {10.1186/1471-2164-10-478},
issn = {1471-2164},
pubmedid = {19835573},
url = {http://www.biomedcentral.com/1471-2164/10/478}
}
@ARTICLE{Zhang2011,
author = {Zhang, Jin-Zhi and Ai, Xiao-Yan and Sun, Lei-Ming and Zhang, Dong-Liang
and Guo, Wen-Wu and Deng, Xiu-Xin and Hu, Chun-Gen},
title = {Transcriptome profile analysis of flowering molecular processes of
early flowering trifoliate orange mutant and the wild-type [Poncirus
trifoliata (L.) Raf.] by massively parallel signature sequencing},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {63},
number = {1},
abstract = {BACKGROUND:After several years in the juvenile phase, trees undergo
flowering transition to become mature (florally competent) trees.
This transition depends on the balanced expression of a complex network
of genes that is regulated by both endogenous and environmental factors.
However, relatively little is known about the molecular processes
regulating flowering transition in woody plants compared with herbaceous
plants.RESULTS:Comparative transcript profiling of spring shoots
after self-pruning was performed on a spontaneously early flowering
trifoliate orange mutant (precocious trifoliate orange, Poncirus
trifoliata) with a short juvenile phase and the wild-type (WT) tree
by using massively parallel signature sequencing (MPSS). A total
of 16,564,500 and 16,235,952 high quality reads were obtained for
the WT and the mutant (MT), respectively. Interpretation of the MPSS
signatures revealed that the total number of transcribed genes in
the MT (31,468) was larger than in the WT (29,864), suggesting that
newly initiated transcription occurs in the MT. Further comparison
of the transcripts revealed that 2735 genes had more than twofold
expression difference in the MT compared with the WT. In addition,
we identified 110 citrus flowering-time genes homologous with known
elements of flowering-time pathways through sequencing and bioinformatics
analysis. These genes are highly conserved in citrus and other species,
suggesting that the functions of the related proteins in controlling
reproductive development may be conserved as well.CONCLUSION:Our
results provide a foundation for comparative gene expression studies
between WT and precocious trifoliate orange. Additionally, a number
of candidate genes required for the early flowering process of precocious
trifoliate orange were identified. These results provide new insight
into the molecular processes regulating flowering time in citrus.},
doi = {10.1186/1471-2164-12-63},
issn = {1471-2164},
pubmedid = {21269450},
url = {http://www.biomedcentral.com/1471-2164/12/63}
}
@ARTICLE{Zhang2009e,
author = {Zhang, Lei and Bowen, Timothy and Grennan-Jones, Fiona and Paddon,
Carol and Giles, Peter and Webber, Jason and Steadman, Robert and
Ludgate, Marian},
title = {Thyrotropin Receptor Activation Increases Hyaluronan Production in
Preadipocyte Fibroblasts: CONTRIBUTORY ROLE IN HYALURONAN ACCUMULATION
IN THYROID DYSFUNCTION},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {26447--26455},
number = {39},
month = sep,
abstract = {The thyrotropin receptor (TSHR) is expressed during lineage-specific
differentiation (e.g. adipogenesis) and is activated by TSH, thyroid-stimulating
antibodies, and gain-of-function mutations (TSHR*). Comparison of
gene expression profiles of nonmodified human preadipocytes (n =
4) with the parallel TSHR* population revealed significant up-regulation
of 27 genes including hyaluronan (HA) synthases (HAS) 1 and 2. The
array data were confirmed by quantitative PCR of HAS1 and HAS2 and
enzyme-linked immunosorbent assay measurement of HA; all values were
significantly increased (p < 0.03) in TSHR*-expressing preadipocytes
(n = 10). Preadipocytes (n = 8) treated with dibutyryl (db)-cAMP
display significantly increased HAS1 and HAS2 transcripts, HAS2 protein,
and HA production (p < 0.02). HAS1 or HAS2 small interfering RNA
treatment of db-cAMP-stimulated preadipocytes (n = 4) produced 80%
knockdown in HAS1 or 61% knockdown in HAS2 transcripts (compared
with scrambled), respectively; the corresponding HA production was
reduced by 49 or 38%. Reporter assays using A293 cells transfected
with HAS1 promoter-driven plasmids containing or not containing the
proximal CRE and treated with db-cAMP revealed that it is functional.
Chromatin immunoprecipitation, using a cAMP-responsive element-binding
protein antibody, of db-cAMP-treated preadipocytes (n = 4) yielded
products for HAS1 and HAS2 with relative fold increases of 3.3 {+/-}
0.8 and 2.6 {+/-} 0.9, respectively. HA accumulates in adipose/connective
tissues of patients with thyroid dysfunction. We investigated the
contributions of TSH and thyroid-stimulating antibodies and obtained
small (9-24%) but significant (p < 0.02) increases in preadipocyte
HA production with both ligands. Similar results were obtained with
a TSHR monoclonal antibody lacking biological activity (p < 0.05).
We conclude that TSHR activation is implicated in HA production in
preadipocytes, which, along with thyroid hormone level variation,
explains the HA overproduction in thyroid dysfunction.},
url = {http://www.jbc.org/cgi/content/abstract/284/39/26447}
}
@ARTICLE{Zhang2004b,
author = {Zhang, Lihong and Chaudhuri, Roy R. and Constantinidou, Chrystala
and Hobman, Jon L. and Patel, Mala D. and Jones, Antony C. and Sarti,
Donatella and Roe, Andrew J. and Vlisidou, Isabella and Shaw, Robert
K. and Falciani, Francesco and Stevens, Mark P. and Gally, David
L. and Knutton, Stuart and Frankel, Gad and Penn, Charles W. and
Pallen, Mark J.},
title = {Regulators Encoded in the Escherichia coli Type III Secretion System
2 Gene Cluster Influence Expression of Genes within the Locus for
Enterocyte Effacement in Enterohemorrhagic E. coli O157:H7},
journal = {Infect. Immun.},
year = {2004},
volume = {72},
pages = {7282--7293},
number = {12},
month = dec,
abstract = {Enterohemorrhagic Escherichia coli (EHEC) O157:H7 subverts host cells
through a type III secretion system encoded by the locus for enterocyte
effacement (LEE). Genome sequencing of this pathotype revealed the
existence of a gene cluster encoding components of a second cryptic
type III secretion system, E. coli type III secretion system 2 (ETT2).
Recently, we showed that the ETT2 gene cluster is present in whole
or in part in the majority of E. coli strains but is unable to encode
a functional secretion system in most strains, including EHEC O157:H7.
However, here we show that mutational inhibition of two regulatory
genes (ECs3720 or etrA and ECs3734 or eivF) from the ETT2 cluster
in EHEC O157:H7 leads to greatly increased secretion of proteins
encoded by the LEE and to increased adhesion to human intestinal
cells. Studies in which transcriptional fusions and microarrays were
used indicated that EtrA and EivF exert profound negative effects
on gene transcription within the LEE. Consistent with these observations,
expression of these regulators in an EHEC O26:H- strain led to suppression
of protein secretion under LEE-inducing conditions. These findings
provide fresh examples of the influence of mobile genetic elements
on regulation of the LEE and of cross talk between type III secretion
system gene clusters. In addition, they provide a cautionary tale
because they show that the effects of regulatory genes can outlive
widespread decay of other genes in a functionally coherent gene cluster,
a phenomenon that we have named the "Cheshire cat effect." It also
seems likely that variations in the ETT2 regulator repertoire might
account for strain-to-strain variation in secretion of LEE-encoded
proteins.},
url = {http://iai.asm.org/cgi/content/abstract/72/12/7282}
}
@ARTICLE{Zhang2006c,
author = {Zhang, Lizhi and Chenwei, Li and Mahmood, Redah and Golen, Kenneth
van and Greenson, Joel and Li, Gangyong and D'Silva, Nisha J. and
Li, Xiangquan and Burant, Charles F. and Logsdon, Craig D. and Simeone,
Diane M.},
title = {Identification of a Putative Tumor Suppressor Gene Rap1GAP in Pancreatic
Cancer},
journal = {Cancer Res.},
year = {2006},
volume = {66},
pages = {898--906},
number = {2},
month = jan,
abstract = {Human chromosome 1p35-p36 has long been suspected to harbor a tumor
suppressor gene in pancreatic cancer and other tumors. We found that
expression of rap1GAP, a gene located in this chromosomal region,
is significantly down-regulated in pancreatic cancer. Only a small
percentage of preneoplastic pancreatic intraductal neoplasia lesions
lost rap1GAP expression, whereas loss of rap1GAP expression occurred
in 60% of invasive pancreatic cancers, suggesting that rap1GAP contributes
to pancreatic cancer progression. In vitro and in vivo studies showed
that loss of rap1GAP promotes pancreatic cancer growth, survival,
and invasion, and may function through modulation of integrin activity.
Furthermore, we showed a high frequency of loss of heterozygosity
of rap1GAP in pancreatic cancer. Collectively, our data identify
rap1GAP as a putative tumor suppressor gene in pancreatic cancer.
(Cancer Res 2006; 66(2): 898-906)},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/2/898}
}
@ARTICLE{Zhang2003,
author = {Zhang, Lihua and Dang, Fuquan and Baba, Yoshinobu},
title = {Microchip electrophoresis-based separation of DNA},
journal = {Journal of Pharmaceutical and Biomedical Analysis},
year = {2003},
volume = {30},
pages = {1645--1654},
number = {6},
month = jan,
abstract = {Miniaturized instruments have developed very quickly in the last decade.
This review is focused on the microchip electrophoresis-based separation
of DNA. Fundamentals, including the chip format, substrates and fabrication
technologies, fluid control, as well as various detection methods,
are summarized. Array electrophoresis microchip and the on-chip integration
of electrophoresis with other systems are introduced as well. In
addition, the application of microchip electrophoresis in DNA sizing,
genetic analysis and DNA sequencing are also presented in this paper.},
issn = {0731-7085},
keywords = {Microchip electrophoresis, Microfabrication, Array electrophoresis
microchip, Genomics, Review},
url = {http://www.sciencedirect.com/science/article/B6TGX-47BX9C3-T/2/1507e5d868c30a00fa421d2ac07a6d87}
}
@ARTICLE{Zhang2006d,
author = {Zhang, Lihua and Dang, Fuquan and Kaji, Noritada and Baba, Yoshinobu},
title = {Fast extraction, amplification and analysis of genes from human blood},
journal = {Journal of Chromatography A},
year = {2006},
volume = {1106},
pages = {175--180},
number = {1-2},
month = feb,
abstract = {In order to shorten the time spent on the sample preparation for gene
analysis, a novel method was proposed through the combination of
fast DNA extraction and purification by Generation capture disk,
amplification by capillary polymerase chain reaction, and confirmation
of amplification products by microchip electrophoresis. With this
method, 3 [mu]L blood was enough to obtain adequate target fragments
in human genes. Under the optimal conditions in each step, the sample
preparation for eight fragments in [beta]-globin gene and four fragments
in ras gene could be finished within 20 min. Since all the experiments
were performed on commercial instruments, this method showed a wide
range of applicability. In addition, other advantages such as fast
speed and low consumption of samples were demonstrated. All these
merits proved that such a combination method was of great potential
for the clinical diagnostics.},
booktitle = {Microseparation Sciences: Perspectives and Recent Advances - With
Recognition of Shigeru Terabe},
issn = {0021-9673},
keywords = {Gene analysis, Polymerase chain reaction, Microchip electrophoresis},
url = {http://www.sciencedirect.com/science/article/B6TG8-4HRMV36-2/2/860662a16e5660221fa42def053253e2}
}
@ARTICLE{Zhang2011h,
author = {Zhang, Lina and Liu, Yuexin and Song, Fengju and Zheng, Hong and
Hu, Limei and Lu, Hong and Liu, Peifang and Hao, Xishan and Zhang,
Wei and Chen, Kexin},
title = {Functional SNP in the microRNA-367 binding site in the 3'UTR of the
calcium channel ryanodine receptor gene 3 (RYR3) affects breast cancer
risk and calcification},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {13653-13658},
number = {33},
abstract = {We have evaluated and provided evidence that the ryanodine receptor
3 gene (RYR3), which encodes a large protein that forms a calcium
channel, is important for the growth, morphology, and migration of
breast cancer cells. A putative binding site for microRNA-367 (miR-367)
exists in the 3'UTR of RYR3, and a genetic variant, rs1044129 A[->]G,
is present in this binding region. We confirmed that miR-367 regulates
the expression of a reporter gene driven by the RYR3 3'UTR and that
the regulation was affected by the RYR3 genotype. A thermodynamic
model based on base pairing and the secondary structure of the RYR3
mRNA and miR-367 miRNA showed that miR-367 had a higher binding affinity
for the A genotype than for the G genotype. The rs1044129 SNP was
genotyped in 1,532 breast cancer cases and 1,600 healthy Chinese
women. The results showed that compared with the AA genotype, G was
a risk genotype for breast cancer development and was also associated
with breast cancer calcification and poor survival. Thus, rs1044129
is a unique SNP that resides in a miRNA-gene regulatory loop that
affects breast cancer risk, calcification, and survival.},
doi = {10.1073/pnas.1103360108},
eprint = {http://www.pnas.org/cgi/reprint/108/33/13653.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/33/13653}
}
@ARTICLE{Zhang2004c,
author = {Zhang, Lu and Lou, Danwen and Jiao, Hongyuan and Zhang, Dongsheng
and Wang, Xinkang and Xia, Ying and Zhang, Jianhua and Xu, Ming},
title = {Cocaine-Induced Intracellular Signaling and Gene Expression Are Oppositely
Regulated by the Dopamine D1 and D3 Receptors},
journal = {J. Neurosci.},
year = {2004},
volume = {24},
pages = {3344--3354},
number = {13},
month = mar,
abstract = {Repeated exposure to cocaine can induce neuroadaptations in the brain.
One mechanism by which persistent changes occur involves alterations
in gene expression mediated by the dopamine receptors. Both the dopamine
D1 and D3 receptors have been shown to mediate gene expression changes.
Moreover, the D1 and D3 receptors are also coexpressed in the same
neurons, particularly in the nucleus accumbens and also caudoputamen
(CPu). Little is known however, whether these two receptors coordinately
regulate gene expression after cocaine administration and the underlying
mechanisms. We have used various gene mutant mice to address this
issue. We show that extracellular signal-regulated kinase (ERK) activation
and c-fos induction in the CPu in response to acute cocaine administration
is mediated by the D1 receptor and inhibited by the D3 receptor.
Moreover, ERK activation mediates acute cocaine-induced expression
of Fos family genes, including c-fos, fosB and fra2. Interestingly,
dynorphin, neogenin, and synaptotagmin VII, genes that possess cAMP-response
element binding protein and AP-1 transcription complex-binding consensus
sequences in their promoters, are also oppositely regulated by the
D1 and D3 receptors after repeated exposure to cocaine. Furthermore,
such regulation depends on proper ERK activation and c-fos function.
These results suggest that the D1 and D3 receptors elicit opposite
regulation of target gene expression by regulating ERK activation
and c-fos induction after acute and chronic cocaine treatment.},
url = {http://www.jneurosci.org/cgi/content/abstract/24/13/3344}
}
@ARTICLE{Zhang2005a,
author = {Zhang, Liping and Rubins, Nir E. and Ahima, Rexford S. and Greenbaum,
Linda E. and Kaestner, Klaus H.},
title = {Foxa2 integrates the transcriptional response of the hepatocyte to
fasting},
journal = {Cell Metabolism},
year = {2005},
volume = {2},
pages = {141--148},
number = {2},
month = aug,
abstract = {Summary Survival during prolonged food deprivation depends on the
activation of hepatic gluconeogenesis. Inappropriate regulation of
this process is a hallmark of diabetes and other metabolic diseases.
Activation of the genes encoding gluconeogenic enzymes is mediated
by hormone-responsive transcription factors such as the cyclic AMP
response element binding protein (CREB) and the glucocorticoid receptor
(GR). Here we show using cell-type-specific gene ablation that the
winged helix transcription factor Foxa2 is required for activation
of the hepatic gluconeogenic program during fasting. Specifically,
Foxa2 promotes gene activation both by cyclic AMP, the second messenger
for glucagon, and glucocorticoids. Foxa2 mediates these effects by
enabling recruitment of CREB and GR to their respective target sites
in chromatin. We conclude that Foxa2 is required for execution of
the hepatic gluconeogenic program by integrating the transcriptional
response of the hepatocyte to hormonal stimulation.},
issn = {1550-4131},
url = {http://www.sciencedirect.com/science/article/B7MFH-4GWJBRJ-B/2/56d5956d4a594a6496b3e0223c0ff650}
}
@ARTICLE{Zhang2008c,
author = {Zhang, Lin and Volinia, Stefano and Bonome, Tomas and Calin, George
Adrian and Greshock, Joel and Yang, Nuo and Liu, Chang-Gong and Giannakakis,
Antonis and Alexiou, Pangiotis and Hasegawa, Kosei and Johnstone,
Cameron N. and Megraw, Molly S. and Adams, Sarah and Lassus, Heini
and Huang, Jia and Kaur, Sippy and Liang, Shun and Sethupathy, Praveen
and Leminen, Arto and Simossis, Victor A. and Sandaltzopoulos, Raphael
and Naomoto, Yoshio and Katsaros, Dionyssios and Gimotty, Phyllis
A. and DeMichele, Angela and Huang, Qihong and Butzow, Ralf and Rustgi,
Anil K. and Weber, Barbara L. and Birrer, Michael J. and Hatzigeorgiou,
Artemis G. and Croce, Carlo M. and Coukos, George},
title = {Genomic and epigenetic alterations deregulate microRNA expression
in human epithelial ovarian cancer},
journal = {PNAS},
year = {2008},
volume = {105},
pages = {7004--7009},
number = {19},
month = may,
abstract = {MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that
function as negative gene regulators. miRNA deregulation is involved
in the initiation and progression of human cancer; however, the underlying
mechanism and its contributions to genome-wide transcriptional changes
in cancer are still largely unknown. We studied miRNA deregulation
in human epithelial ovarian cancer by integrative genomic approach,
including miRNA microarray (n = 106), array-based comparative genomic
hybridization (n = 109), cDNA microarray (n = 76), and tissue array
(n = 504). miRNA expression is markedly down-regulated in malignant
transformation and tumor progression. Genomic copy number loss and
epigenetic silencing, respectively, may account for the down-regulation
of {approx}15% and at least {approx}36% of miRNAs in advanced ovarian
tumors and miRNA down-regulation contributes to a genome-wide transcriptional
deregulation. Last, eight miRNAs located in the chromosome 14 miRNA
cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor
genes. Therefore, our results suggest that miRNAs may offer new biomarkers
and therapeutic targets in epithelial ovarian cancer.},
url = {http://www.pnas.org/cgi/content/abstract/105/19/7004}
}
@ARTICLE{Zhang2010e,
author = {Zhang, L.-S. and Ma, H.-W. and Greyner, H. J. and Zuo, W. and Mummert,
M. E.},
title = {Inhibition of cell proliferation by CD44: Akt is inactivated and
EGR-1 is down-regulated},
journal = {Cell Proliferation},
year = {2010},
volume = {43},
pages = {385--395},
number = {4},
abstract = {Abstract Objective:  CD44 is a transmembrane glycoprotein and can
facilitate signal transduction by serving as a platform for molecular
recruitment and assembly. A number of studies have suggested that
CD44 can either positively or negatively regulate cell proliferation.
The purpose of this study was to investigate how CD44 can inhibit
cell proliferation. Materials and methods:  We engineered E6.1
Jurkat cells to express CD44. Importantly, these cells lack endogenous
CD44 expression. Molecular pathways involved with cell proliferation
were studied using RT2-PCR array, siRNA, Western blotting and by
employing pharmacological inhibitors of ERK1/2, p38 and the PI3K/Akt
pathways. Results:  We found that CD44 expression significantly
inhibited cell proliferation and down-regulated EGR-1 expression
and EGR-1 targets cyclin D1 and cyclin D2. Transfection of control
E6.1 Jurkat cells with EGR-1 siRNA also inhibited cell proliferation,
confirming its role. Disruption of the PI3K/Akt pathway with pharmacological
inhibitors reduced both EGR-1 expression and cell proliferation,
recapitulating the properties of CD44 expressing cells. Akt was hypophosphorylated
in cells expressing CD44 showing its potential role in negatively
regulating Akt activation. Strikingly, constitutively active Akt
rescued the proliferation defect showing requirement for active Akt,
in our system. Conclusion:  Our results suggest a novel pathway
by which CD44 inactivates Akt, down-regulates EGR-1 expression and
inhibits cell proliferation.},
issn = {1365-2184},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2184.2010.00689.x}
}
@ARTICLE{Zhang2011k,
author = {Zhang, Mengxian and Kleber, Susanne and Rohrich, Manuel and Timke,
Carmen and Han, Na and Tuettenberg, Jochen and Martin-Villalba, Ana
and Debus, Juergen and Peschke, Peter and Wirkner, Ute and Lahn,
Michael and Huber, Peter E.},
title = {Blockade of TGF-{beta} Signaling by the TGF{beta}R-I Kinase Inhibitor
LY2109761 Enhances Radiation Response and Prolongs Survival in Glioblastoma},
journal = {Cancer Res.},
year = {2011},
volume = {71},
pages = {7155-7167},
number = {23},
abstract = {Glioblastoma multiforme (GBM) is a highly aggressive primary brain
tumor that tends to be resistant to the ionizing radiotherapy used
to treat it. Because TGF-{beta} is a modifier of radiation responses,
we conducted a preclinical study of the antitumor effects of the
TGF-{beta} receptor (TGF{beta}R) I kinase inhibitor LY2109761 in
combination with radiotherapy. LY2109761 reduced clonogenicity and
increased radiosensitivity in GBM cell lines and cancer stem-like
cells, augmenting the tumor growth delay produced by fractionated
radiotherapy in a supra-additive manner in vivo. In an orthotopic
intracranial model, LY2109761 significantly reduced tumor growth,
prolonged survival, and extended the prolongation of survival induced
by radiation treatment. Histologic analyses showed that LY2109761
inhibited tumor invasion promoted by radiation, reduced tumor microvessel
density, and attenuated mesenchymal transition. Microarray-based
gene expression analysis revealed signaling effects of the combinatorial
treatments that supported an interpretation of their basis. Together,
these results show that a selective inhibitor of the TGF{beta}R-I
kinase can potentiate radiation responses in glioblastoma by coordinately
increasing apoptosis and cancer stem-like cells targeting while blocking
DNA damage repair, invasion, mesenchymal transition, and angiogenesis.
Our findings offer a sound rationale for positioning TGF{beta}R kinase
inhibitors as radiosensitizers to improve the treatment of glioblastoma.
Cancer Res; 71(23); 7155-67. (C)2011 AACR.},
doi = {10.1158/0008-5472.CAN-11-1212},
eprint = {http://cancerres.aacrjournals.org/cgi/reprint/71/23/7155.pdf},
url = {http://cancerres.aacrjournals.org/cgi/content/abstract/71/23/7155}
}
@ARTICLE{Zhang2003a,
author = {Zhang, Meng and Lidstrom, Mary E.},
title = {Promoters and transcripts for genes involved in methanol oxidation
in Methylobacterium extorquens AM1},
journal = {Microbiology},
year = {2003},
volume = {149},
pages = {1033--1040},
number = {4},
month = apr,
abstract = {Twenty-five genes are involved in methanol oxidation to formaldehyde
by the methanol dehydrogenase system in the facultative methylotroph
Methylobacterium extorquens AM1 organized in five gene clusters.
RT-PCR was used to assess the transcripts for the main gene clusters
that encode methanol dehydrogenase and proteins required for its
activity (mxaFGJIRSACKLDEHB), and the enzymes that are required for
the synthesis of the methanol dehydrogenase prosthetic group, pyrroloquinoline
quinone (pqqABC/DE and the pqqFG cluster). In both cases, positive
bands were obtained corresponding to mRNA spanning each of the genes
in the cluster, but not across the first and last genes and the gene
immediately upstream or downstream of the cluster, respectively.
These results suggest that these three gene clusters are each transcribed
as a single operon. Confirmation was obtained by cloning a number
of intergenic regions into a promoter probe vector. None of these
regions showed significant promoter activity. Promoter regions were
analysed for mxaF, pqqA, orf181 upstream of pqqFG, and mxaW, a gene
located upstream of mxaF and divergently transcribed. The promoter
regions for these genes were defined to within 100, 46, 124 and 146
bp, respectively, and the two unknown transcriptional start sites
were determined, for mxaW and orf181. Alignment of these promoter
regions suggests that they all may be transcribed by the{sigma} 70
orthologue in M. extorquens AM1.},
url = {http://mic.sgmjournals.org/cgi/content/abstract/149/4/1033}
}
@ARTICLE{Zhang2008d,
author = {Zhang, Min and Maddala, Rupalatha and Rao, Ponugoti Vasantha},
title = {Novel molecular insights into RhoA GTPase-induced resistance to aqueous
humor outflow through the trabecular meshwork},
journal = {Am J Physiol Cell Physiol},
year = {2008},
volume = {295},
pages = {C1057--1070},
number = {5},
month = nov,
abstract = {Impaired drainage of aqueous humor through the trabecular meshwork
(TM) culminating in increased intraocular pressure is a major risk
factor for glaucoma, a leading cause of blindness worldwide. Regulation
of aqueous humor drainage through the TM, however, is poorly understood.
The role of RhoA GTPase-mediated actomyosin organization, cell adhesive
interactions, and gene expression in regulation of aqueous humor
outflow was investigated using adenoviral vector-driven expression
of constitutively active mutant of RhoA (RhoAV14). Organ-cultured
anterior segments from porcine eyes expressing RhoAV14 exhibited
significant reduction of aqueous humor outflow. Cultured TM cells
expressing RhoAV14 exhibited a pronounced contractile morphology,
increased actin stress fibers, and focal adhesions and increased
levels of phosphorylated myosin light chain (MLC), collagen IV, fibronectin,
and laminin. cDNA microarray analysis of RNA extracted from RhoAV14-expressing
human TM cells revealed a significant increase in the expression
of genes encoding extracellular matrix (ECM) proteins, cytokines,
integrins, cytoskeletal proteins, and signaling proteins. Conversely,
various ECM proteins stimulated robust increases in phosphorylation
of MLC, paxillin, and focal adhesion kinase and activated Rho GTPase
and actin stress fiber formation in TM cells, indicating a potential
regulatory feedback interaction between ECM-induced mechanical strain
and Rho GTPase-induced isometric tension in TM cells. Collectively,
these data demonstrate that sustained activation of Rho GTPase signaling
in the aqueous humor outflow pathway increases resistance to aqueous
humor outflow through the trabecular pathway by influencing the actomyosin
assembly, cell adhesive interactions, and the expression of ECM proteins
and cytokines in TM cells.},
url = {http://ajpcell.physiology.org/cgi/content/abstract/295/5/C1057}
}
@ARTICLE{Zhang2008e,
author = {Zhang, Mingliang and Pritchard, Meredith R. and Middleton, Frank
A. and Horton, Jason A. and Damron, Timothy A.},
title = {Microarray analysis of perichondral and reserve growth plate zones
identifies differential gene expressions and signal pathways},
journal = {Bone},
year = {2008},
volume = {43},
pages = {511--520},
number = {3},
month = sep,
abstract = {In the growth plate, the reserve and perichondral zones have been
hypothesized to have similar functions, but their exact functions
are poorly understood. Our hypothesis was that significant differential
gene expression exists between perichondral and reserve chondrocytes
that may differentiate the respective functions of these two zones.
Normal Sprague-Dawley rat growth plate chondrocytes from the perichondral
zone (PC) and reserve zone (RZ) were isolated by laser microdissection
and then subjected to microarray analysis. In order to most comprehensively
capture the unique features of the two zones, we analyzed both the
most highly expressed genes and those that were most significantly
different from the proliferative zone (PZ) as a single comparator.
Confirmation of the differential expression of selected genes was
done by quantitative real-time RT-PCR. A total of 8 transcripts showing
high expression unique to the PC included translationally-controlled
tumor protein (Tpt1), connective tissue growth factor (Ctgf), mortality
factor 4 (Morf4l1), growth arrest specific 6 (Gas6), type V procollagen
(Col5a2), frizzled-related protein (Frzb), GDP-dissociation inhibitor
2 (Gdi2) and Jun D proto-oncogene (Jund). In contrast, 8 transcripts
showing unique high expression in the RZ included hyaluronan and
proteoglycan link protein 1 (Hapln1), hemoglobin beta-2 subunit,
type I procollagen (Col1a2), retinoblastoma binding protein 4 (LOC685491),
Sparc-related modular calcium binding 2 (Smoc2), and calpastatin
(Cast). Other genes were highly expressed in cells from both PC and
RZ zones, including collagen II, collagen IX, catenin (cadherin associated
protein) beta 1, eukaryotic translation elongation factor, high mobility
group, ribosomal protein, microtubule-associated protein, reticulocalbin,
thrombospondin, retinoblastoma binding protein, carboxypeptidase
E, carnitine palmitoyltransferase 1, cysteine rich glycoprotein,
plexin B2 (Plxnb2), and gap junction membrane channel protein. Functional
classification of the most highly expressed transcripts were analyzed,
and the pathway analysis indicated that ossification, bone remodeling,
and cartilage development were uniquely enriched in the PC whereas
both the PC and RZ showed pathway enrichment for skeletal development,
extracellular matrix structural constituent, proteinaceous extracellular
matrix, collagen, extracellular matrix, and extracellular matrix
part pathways. We conclude that differential gene expression exists
between the RZ and PC chondrocytes and these differentially expressed
genes have unique roles to play corresponding to the function of
their respective zones.},
issn = {8756-3282},
keywords = {Growth plate, Microarray, Chondrocytes, Rat, Bone},
url = {http://www.sciencedirect.com/science/article/B6T4Y-4SG4HMW-2/2/15d15c87183f7e511cb31a6ed22b4297}
}
@ARTICLE{Zhang2011j,
author = {Zhang, Qisen and Pettolino, Filomena A. and Dhugga, Kanwarpal S.
and Rafalski, J. Antoni and Tingey, Scott and Taylor, Jillian and
Shirley, Neil J. and Hayes, Kevin and Beatty, Mary and Abrams, Suzanne
R. and Zaharia, L. Irina and Burton, Rachel A. and Bacic, Antony
and Fincher, Geoffrey B.},
title = {Cell Wall Modifications in Maize Pulvini in Response to Gravitational
Stress},
journal = {Plant Physiology},
year = {2011},
volume = {156},
pages = {2155-2171},
number = {4},
abstract = {Changes in cell wall polysaccharides, transcript abundance, metabolite
profiles, and hormone concentrations were monitored in the upper
and lower regions of maize (Zea mays) pulvini in response to gravistimulation,
during which maize plants placed in a horizontal position returned
to the vertical orientation. Heteroxylan levels increased in the
lower regions of the pulvini, together with lignin, but xyloglucans
and heteromannan contents decreased. The degree of substitution of
heteroxylan with arabinofuranosyl residues decreased in the lower
pulvini, which exhibited increased mechanical strength as the plants
returned to the vertical position. Few or no changes in noncellulosic
wall polysaccharides could be detected on the upper side of the pulvinus,
and crystalline cellulose content remained essentially constant in
both the upper and lower pulvinus. Microarray analyses showed that
spatial and temporal changes in transcript profiles were consistent
with the changes in wall composition that were observed in the lower
regions of the pulvinus. In addition, the microarray analyses indicated
that metabolic pathways leading to the biosynthesis of phytohormones
were differentially activated in the upper and lower regions of the
pulvinus in response to gravistimulation. Metabolite profiles and
measured hormone concentrations were consistent with the microarray
data, insofar as auxin, physiologically active gibberellic acid,
and metabolites potentially involved in lignin biosynthesis increased
in the elongating cells of the lower pulvinus.},
doi = {10.1104/pp.111.179606},
eprint = {http://www.plantphysiol.org/cgi/reprint/156/4/2155.pdf},
url = {http://www.plantphysiol.org/cgi/content/abstract/156/4/2155}
}
@ARTICLE{Zhang2011g,
author = {Zhang, Rongzhen and Hadlock, Kenneth G. and Do, Hien and Yu, Stephanie
and Honrada, Ronald and Champion, Stacey and Forshew, Dallas and
Madison, Catherine and Katz, Jonathan and Miller, Robert G. and McGrath,
Michael S.},
title = {Gene expression profiling in peripheral blood mononuclear cells from
patients with sporadic amyotrophic lateral sclerosis (sALS)},
journal = {Journal of Neuroimmunology},
year = {2011},
volume = {230},
pages = {114--123},
number = {1-2},
month = jan,
abstract = {The aim of this study was to identify gene expression profiles in
peripheral blood mononuclear cells (PBMCs) from sporadic amyotrophic
lateral sclerosis (sALS) patients to gain insights into the pathogenesis
of ALS. We found that upregulation of LPS/TLR4-signaling associated
genes was observed in the PMBCs from sALS patients after short-term
cultivation, and that elevated levels of gene expression correlated
with degree of peripheral blood monocyte activation and plasma LPS
levels in sALS. Similar patterns of gene expression were reproduced
in LPS stimulated PBMCs from healthy controls. These data suggest
that chronic monocyte/macrophage activation may be through LPS/TLR4-signaling
pathways in ALS.},
issn = {0165-5728},
keywords = {Amyotrophic lateral sclerosis (ALS), Monocyte/macrophage activation,
Lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4)},
url = {http://www.sciencedirect.com/science/article/pii/S0165572810003760}
}
@ARTICLE{Zhang2011d,
author = {Shuguang Zhang and Ramesh T. Gunaratna and Xiufeng Zhang and Fares
Najar and Yang Wang and Bruce Roe and Haobo Jiang},
title = {Pyrosequencing-based expression profiling and identification of differentially
regulated genes from Manduca sexta, a lepidopteran model insect},
journal = {Insect Biochemistry and Molecular Biology},
year = {2011},
volume = {41},
pages = {733 - 746},
number = {9},
abstract = {Although Manduca sexta has significantly contributed to our knowledge
on a variety of insect physiological processes, the lack of its genome
sequence hampers the large-scale gene discovery, transcript profiling,
and proteomic analysis in this biochemical model species. Here we
report our implementation of the RNA-Seq cDNA sequencing approach
based on massively parallel pyrosequencing, which allows us to categorize
transcripts based on their relative abundances and to discover process-
or tissue-specifically regulated genes simultaneously. We obtained
1,821,652 reads with an average length of 289Â bp per read from fat
body and hemocytes of naïve and microbe-injected M. sexta larvae.
After almost all (92.1%) of these reads were assembled into 19,020
contigs, we identified 528 contigs whose relative abundances increased
at least 5- and 8-fold in fat body and hemocytes, respectively, after
the microbial challenge. Polypeptides encoded by these contigs include
pathogen recognition receptors, extracellular and intracellular signal
mediators and regulators, antimicrobial peptides, and proteins with
no known sequence but likely participating in defense in novel ways.
We also found 250 and 161 contigs that were preferentially expressed
in fat body and hemocytes, respectively. Furthermore, we integrated
data from our previous study and generated a sequence database to
support future gene annotation and proteomic analysis in M. sexta.
In summary, we have successfully established a combined approach
for gene discovery and expression profiling in organisms lacking
known genome sequences.},
doi = {10.1016/j.ibmb.2011.05.005},
issn = {0965-1748},
keywords = {Insect immunity},
url = {http://www.sciencedirect.com/science/article/pii/S096517481100107X}
}
@ARTICLE{Zhang2010,
author = {Zhang, Shize and Shukle, Richard and Mittapalli, Omprakash and Zhu,
Yu Cheng and Reese, John C. and Wang, Haiyan and Hua, Bao-Zhen and
Chen, Ming-Shun},
title = {The gut transcriptome of a gall midge, Mayetiola destructor},
journal = {Journal of Insect Physiology},
year = {2010},
volume = {56},
pages = {1198--1206},
number = {9},
month = sep,
abstract = {The Hessian fly, Mayetiola destructor, is a serious pest of wheat
and an experimental organism for the study of gall midge-plant interactions.
In addition to food digestion and detoxification, the gut of Hessian
fly larvae is also an important interface for insect-host interactions.
Analysis of the genes expressed in the Hessian fly larval gut will
enhance our understanding of the overall gut physiology and may also
lead to the identification of critical molecules for Hessian fly-host
plant interactions. Over 10,000 Expressed Sequence Tags (ESTs) were
generated and assembled into 2007 clusters. The most striking feature
of the Hessian fly larval transcriptome is the existence of a large
number of transcripts coding for so-called small secretory proteins
(SSP) with amino acids less than 250. Eleven of the 30 largest clusters
were SSP transcripts with the largest cluster containing 11.3% of
total ESTs. Transcripts coding for diverse digestive enzymes and
detoxification proteins were also identified. Putative digestive
enzymes included trypsins, chymotrypsins, cysteine proteases, aspartic
protease, endo-oligopeptidase, aminopeptidases, carboxypeptidases,
and [alpha]-amylases. Putative detoxification proteins included cytochrome
P450s, glutathione S-transferases, peroxidases, ferritins, a catalase,
peroxiredoxins, and others. This study represents the first global
analysis of gut transcripts from a gall midge. The identification
of a large number of transcripts coding for SSPs, digestive enzymes,
detoxification proteins in the Hessian fly larval gut provides a
foundation for future studies on the functions of these genes.},
issn = {0022-1910},
keywords = {Hessian fly, Mayetiola destructor, Gut, Secretory proteins, Salivary
glands, Transcriptome},
url = {http://www.sciencedirect.com/science/article/B6T3F-4YRX4D5-1/2/7acbd7b06dc5ed04895f2cb0decb21be}
}
@ARTICLE{Zhang2010g,
author = {Zhang, Shougong and Zhou, Jian and Han, Suying and Yang, Wenhua and
Li, Wanfeng and Wei, Huali and Li, Xinmin and Qi, Liwang},
title = {Four abiotic stress-induced miRNA families differentially regulated
in the embryogenic and non-embryogenic callus tissues of Larix leptolepis},
journal = {Biochemical and Biophysical Research Communications},
year = {2010},
volume = {398},
pages = {355--360},
number = {3},
month = jul,
abstract = {Somatic embryogenesis involves complex molecular signaling pathways.
Deregulation of these signaling pathways can transform the embryogenic
callus to non-embryogenic callus. To investigate the miRNA regulation
underlying this detrimental transformation in Japanese Larch (Larix
leptolepis), we compared miRNA expression profiles between embryogenic
and non-embryogenic callus at day 3 and day 14 after sub-culture.
Four miRNA families dominated the 165 differentially expressed miRNAs
between embryogenic and non-embryogenic callus. Of the four, miR171
was up-regulated, and miR159, miR169, and miR172 were down-regulated
in the embryogenic callus. These four families are all abiotic stress-induced
miRNAs, and all target transcription factors that regulate a group
of genes important for cell differentiation and development, including
scarecrow-like (SCL) transcription factor (miR171), apetala2 (miR172),
MYB transcription factors (miR159), and NF-YA transcription factor
(miR169). Three down-regulated miRNA families in the embryogenic
callus are also regulated by ABA, which further shed light into the
potential mechanisms underlying the transformation of the embryogenic
competence in L. leptolepis. This study represents the first report
on the miRNA regulation of the embryogenic and non-embryogenic callus
in plant, and thus these four miRNA families provide important clues
for further functional investigation.},
issn = {0006-291X},
keywords = {Larix leptolepis, miRNA regulation, Embryogenesis, miR171, miR172},
url = {http://www.sciencedirect.com/science/article/B6WBK-50CDSH9-1/2/9706fd0a969605262ced2621ca8c2cee}
}
@ARTICLE{Zhang2006e,
author = {Zhang, Tian-Jiao and Hoffman, Brad G. and Ruiz de Algara, Teresa
and Helgason, Cheryl D.},
title = {SAGE reveals expression of Wnt signalling pathway members during
mouse prostate development},
journal = {Gene Expression Patterns},
year = {2006},
volume = {6},
pages = {310--324},
number = {3},
month = mar,
abstract = {To identify genes and pathways not previously implicated in the mesenchymal-epithelial
(M/E) interactions that are critical for normal mouse prostate development,
we constructed six serial analysis of gene expression (SAGE) libraries.
Bioinformatic analyses revealed expression of various members of
numerous signalling pathways and the differential expression of several
members of the wingless-related MMTV integration site (Wnt) signalling
pathway. This pathway has not been previously implicated in prostate
development thus expression of selected Wnt pathway members in the
developing prostate was confirmed by RT-qPCR. Of particular interest,
an antagonist of the Wnt pathway, secreted frizzled related protein
2 (Sfrp2), was highly expressed in the early prostate libraries and
down regulated at later developmental stages. The expression levels
of four Wnt ligands reported to interact with Sfrp2 were, therefore,
examined by RT-qPCR. We found that only Wnt4 transcripts were detectable
in the developing prostate. Expression of Sfrp2 was validated using
RT-qPCR and localization of Sfrp2 transcripts and protein was carried
out using in situ hybridization and immunofluorescence, respectively.
These studies provide the first evidence that Wnt pathway members
are expressed in the developing prostate. Functional analyses are
now required to establish the biological significance of this observation.},
issn = {1567-133X},
keywords = {Mouse, Prostate, Development, SAGE, Wnt, Sfrp2, Signalling pathways,
Mesenchymal-epithelial interactions},
url = {http://www.sciencedirect.com/science/article/B6W8W-4HWX914-3/2/19908df79349f828667790e6d9f8cb62}
}
@ARTICLE{Zhang2008f,
author = {Zhang, Wei and Della-Fera, Mary Anne and Hartzell, Diane L. and Hausman,
Dorothy and Baile, Clifton A.},
title = {Adipose tissue gene expression profiles in ob/ob mice treated with
leptin},
journal = {Life Sciences},
year = {2008},
volume = {83},
pages = {35--42},
number = {1-2},
month = jul,
abstract = {Leptin plays a critical role in regulating body weight, lipid metabolism,
apoptosis and microvasculature of adipose tissue. To explore multiple
signaling pathways of leptin action on adipose tissue, real-time
PCR utilizing TaqMan® low-density arrays was performed to compare
mRNA expression in adipose tissue of ob/ob mice treated with vehicle
or leptin (2.5 [mu]g/d or 10 [mu]g/d) for 14 days via subcutaneous
osmotic minipumps. Of the 24 target genes selected for characterization,
many were differentially expressed between control ob/ob mice and
leptin-treated ob/ob mice. Increases in mRNA expression were found
for hormone sensitive lipase (HSL), uncoupling protein 2 (UCP2),
adrenergic receptor 3 (ADR3), mitofusin 2 (Mfn2), sirtuin 3 (Sirt3),
transcription factor sterol regulatory element binding factor 1 (SREBF1),
Bcl-2, Bax, Caspase 3, tumor necrosis factor [alpha] (TNF[alpha]),
adiponectin and angiopoietin 2 (Ang-2). Decreases in expression were
found for stearoyl-coenzyme A desaturase 1 (SCD1), fatty acid synthase
(FAS), and retinol binding protein 4 (RBP4). There were no changes
in expression of transcription factors involved in adipocyte differentiation
(C/EBP[alpha], PPAR[alpha], and PPAR[gamma]). These results confirm
that alterations in the expression of specific adipose tissue genes
including those associated with the promotion of lipid mobilization,
energy dissipation, and apoptosis may mediate leptin-induced fat
loss in ob/ob mice.},
issn = {0024-3205},
keywords = {Apoptosis, Lipolysis, Lipogenesis, Angiogenesis},
url = {http://www.sciencedirect.com/science/article/B6T99-4SGD506-1/2/67cc8411512c12c5bb89031914807abd}
}
@ARTICLE{Zhang2008g,
author = {Zhang, Wei and Duan, Shiwei and Kistner, Emily O. and Bleibel, Wasim
K. and Huang, R. Stephanie and Clark, Tyson A. and Chen, Tina X.
and Schweitzer, Anthony C. and Blume, John E. and Cox, Nancy J. and
Dolan, M. Eileen},
title = {Evaluation of Genetic Variation Contributing to Differences in Gene
Expression between Populations},
journal = {The American Journal of Human Genetics},
year = {2008},
volume = {82},
pages = {631--640},
number = {3},
month = mar,
abstract = {Gene expression is a complex quantitative trait partially regulated
by genetic variation in DNA sequence. Population differences in gene
expression could contribute to some of the observed differences in
susceptibility to common diseases and response to drug treatments.
We characterized gene expression in the full set of HapMap lymphoblastoid
cell lines derived from individuals of European and African ancestry
for 9156 transcript clusters (gene-level) evaluated with the Affymetrix
GeneChip Human Exon 1.0 ST Array. Gene expression was found to differ
significantly between these samples for 383 transcript clusters.
Biological processes including ribosome biogenesis and antimicrobial
humoral response were found to be enriched in these differential
genes, suggesting their possible roles in contributing to the population
differences at a higher level than that of mRNA expression and in
response to environmental information. Genome-wide association studies
for local or distant genetic variants that correlate with the differentially
expressed genes enabled identification of significant associations
with one or more single-nucleotide polymorphisms (SNPs), consistent
with the hypothesis that genetic factors and not simply population
identity or other characteristics (age of cell lines, length of culture,
etc.) contribute to differences in gene expression in these samples.
Our results provide a comprehensive view of the genes differentially
expressed between populations and the enriched biological processes
involved in these genes. We also provide an evaluation of the contributions
of genetic variation and nongenetic factors to the population differences
in gene expression.},
issn = {0002-9297},
url = {http://www.sciencedirect.com/science/article/B8JDD-4RY1NS0-1/2/6bd2d7d05c31d0e2c0a804959b20fec0}
}
@ARTICLE{Zhang2010i,
author = {Zhang, Weiping and Murphy, Caroline and Sieburth, Leslie E.},
title = {Conserved RNaseII domain protein functions in cytoplasmic mRNA decay
and suppresses Arabidopsis decapping mutant phenotypes},
journal = {PNAS},
year = {2010},
volume = {107},
pages = {15981--15985},
number = {36},
month = sep,
abstract = {Both transcription and RNA decay are critical for normal gene regulation.
Arabidopsis mutants with defects in VARICOSE (VCS), a decapping complex
scaffold protein, lack mRNA decapping and 5'-to-3' decay. These mutants
show either severe or suppressed phenotypes, depending on the Arabidopsis
accession. Here, we show that the molecular basis for this variation
is the SUPPRESSOR OF VARICOSE (SOV), a locus that encodes a conserved,
cytoplasmically localized RRP44-like RNaseII-domain protein. In vivo
RNA decay assays suggest that active forms of this protein carry
out decay on mRNA substrates that overlap with those of the decapping
complex. Members of this conserved gene family encode proteins lacking
the PIN domain, suggesting that SOV is not a functional component
of the RNA exosome.},
url = {http://www.pnas.org/cgi/content/abstract/107/36/15981}
}
@BOOK{Zhang2005b,
title = {Microarray Production: Quality of DNA and Printing},
publisher = {John Wiley \& Sons, Inc.},
year = {2005},
author = {Zhang, Wei and Shmulevich, Ilya and Astola, Jaakko},
pages = {17--40},
abstract = {Summary 10.1002/0471728543.ch2.abs This chapter includes the following
topics:},
booktitle = {Microarray Quality Control},
issn = {9780471728542},
keywords = {CDNA microarrays, array printing, CDNA clones, oligonucleotide arrays,
polymerase chain reaction (PCR)},
url = {http://dx.doi.org/10.1002/0471728543.ch2}
}
@ARTICLE{Zhang2011l,
author = {Zhang, Wei and Tan, Shenglan and Paintsil, Elijah and Dutschman,
Ginger E. and Gullen, Elizabeth A. and Chu, Edward and Cheng, Yung-Chi},
title = {Analysis of deoxyribonucleotide pools in human cancer cell lines
using a liquid chromatography coupled with tandem mass spectrometry
technique},
journal = {Biochemical Pharmacology},
year = {2011},
volume = {824,4},
pages = {411-417},
abstract = {Endogenous ribonucleotides and deoxyribonucleotides play a critical
role in cell function, and determination of their levels is of fundamental
importance in understanding key cellular processes involved in energy
metabolism and molecular and biochemical signaling pathways. In this
study, we determined the respective ribonucleotide and deoxyribonucleotide
pool sizes in different human cell lines using a simple sample preparation
method and LC/MS/MS. This assay was used to determine alterations
in deoxyribonucleotide pools in human pancreatic PANC-1 cells in
response to hypoxia and to treatment with either hydroxyurea or aphidicolin.
The levels of all deoxyribonucleotide metabolites decreased with
hypoxia treatment, except for dUMP, which increased by two-fold.
This LC/MS/MS assay is simple, fast, and sensitive, and it represents
a significant advance over previously published methodologies.},
issn = {0006-2952},
keywords = {ribonucleotides, deoxyribonucleotides, LC/MS/MS, hypoxia, hydroxyurea,
aphidicolin},
url = {http://www.sciencedirect.com/science/article/pii/S0006295211003029}
}
@ARTICLE{Zhang2003b,
author = {Zhang, Xin A. and He, Bo and Zhou, Bin and Liu, Li},
title = {Requirement of the p130CAS-Crk Coupling for Metastasis Suppressor
KAI1/CD82-mediated Inhibition of Cell Migration},
journal = {J. Biol. Chem.},
year = {2003},
volume = {278},
pages = {27319--27328},
number = {29},
month = jul,
abstract = {KAI1/CD82 protein is a member of the tetraspanin superfamily and has
been rediscovered as a cancer metastasis suppressor. The mechanism
of KAI1/CD82-mediated suppression of cancer metastasis remains to
be established. In this study, we found that migration of the metastatic
prostate cancer cell line Du145 was substantially inhibited when
KAI1/CD82 was expressed. The expression of focal adhesion kinase
(FAK) and Lyn, a Src family tyrosine kinase and substrate of FAK,
was up-regulated at both RNA and protein levels upon KAI1/CD82 expression.
The activation of FAK and Lyn, however, remained unchanged in Du145-KAI1/CD82
cells. As a downstream target of FAK-Lyn signaling, the p130CAS (Crk-associated
substrate) protein was decreased upon the expression of KAI1/CD82.
Consequently, less p130CAS-CrkII complex, which functions as a "molecular
switch" in cell motility, was formed in Du145-KAI1/CD82 cells. To
confirm that the p130CAS-CrkII complex is indeed important for the
motility inhibition by KAI1/CD82, overexpression of p130CAS in Du145-KAI1/CD82
cells increased the formation of p130CAS-CrkII complex and largely
reversed the KAI1/CD82-mediated inhibition of cell motility. Taken
together, our studies indicate the following: 1) signaling of FAK-Lyn-p130CAS-CrkII
pathway is altered in KAI1/CD82-expressing cells, and 2) p130CAS-CrkII
coupling is required for KAI1/CD82-mediated suppression of cell motility.},
url = {http://www.jbc.org/cgi/content/abstract/278/29/27319}
}
@ARTICLE{Zhang2008h,
author = {Zhang, Xinyuan and Bao, Shisan and Lai, Donna and Rapkins, Robert
W. and Gillies, Mark C.},
title = {Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal
Barrier Through Differential Regulation of VEGF-A and Its Receptors
in Early Diabetic Rat Retinas},
journal = {Diabetes},
year = {2008},
volume = {57},
pages = {1026--1033},
number = {4},
month = apr,
abstract = {OBJECTIVETo elucidate the mechanism of the unique beneficial effect
of intravitreal steroid therapy on diabetic macular edema, we investigated
the effect of locally administered triamcinolone acetonide (TA) on
the expression of vascular endothelial growth factor (VEGF)-A and
its receptors in retinas of rats with streptozotocin (STZ)-induced
diabetes. We then correlated the expression of these proteins with
breakdown of the blood-retinal barrier (BRB). RESEARCH DESIGN AND
METHODSThirty-two eyes of 16 diabetic and nondiabetic rats were divided
into four groups. TA was injected into the vitreous of the right
eye, and saline was injected into the left eye (control) 3.5 weeks
after induction of diabetes. Retinas were harvested 48 h following
treatment. mRNA and protein expression of VEGF-A, VEGF-A receptor
1 (fms-like tyrosine kinase [FLT]-1), and VEGF-A receptor 2 (fetal
liver kinase [FLK]-1) were determined by real-time RT-PCR and immunohistochemistry.
BRB permeability was quantitated by measuring extravasated endogenous
albumin and retinal thickness. RESULTSDiabetes-induced retinal thickness
and albumin extravasation were significantly reduced in TA-treated
diabetic retinas to a level similar to that in sham-treated nondiabetic
eyes. A close correlation between albumin leakage and increased expression
of both Vegf-a and Flk-1 was noted in the diabetic retinas. TA downregulated
the expression of Vegf-a and Flk-1 but upregulated the expression
of Flt-1. TA did not alter the expression of these genes in nondiabetic
retinas. CONCLUSIONSIntravitreal injection of TA stabilizes the BRB
in association with regulation of Vegf-a, Flk-1, and Flt-1 expression
in retinas in the early stages of diabetes.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/57/4/1026}
}
@ARTICLE{Zhang2010h,
author = {Zhang, Xiaomei and Bocca, Silvina and Franchi, Anahi and Anderson,
Sandra and Kaur, Mandeep and Bajic, Vladimir B. and Oehninger, Sergio},
title = {Do GnRH analogues directly affect human endometrial epithelial cell
gene expression?},
journal = {Mol. Hum. Reprod.},
year = {2010},
volume = {16},
pages = {347--360},
number = {5},
month = may,
abstract = {We examined whether Gonadotrophin-releasing hormone (GnRH) analogues
[leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene
expression in Ishikawa cells used as surrogate for human endometrial
epithelial cells in vitro. The specific aims were: (i) to study the
modulatory effect of GnRH analogues by RT-PCR [in the absence and
presence of E2 and P4, and cyclic adenosine monophosphate (cAMP)]
on mRNA expression of genes modulated during the window of implantation
in GnRH analogues/rFSH-treated assisted reproductive technology cycles
including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A),
PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to
analyze the 5'-flanking regions of such genes for the presence of
putative steroid-response elements [estrogen-response elements (EREs)
and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin-
and expressed ER{alpha}, ER{beta}, PR and GnRH-R proteins. At 6 and
24 h, neither LA nor GA alone had an effect on gene expression. GnRH
analogues alone or following E2 and/or P4 co-incubation for 24 h
also had no effect on gene expression, but P4 significantly increased
expression of CHMP1A. E2 + P4 treatment for 4 days, alone or followed
by GA, had no effect, but E2 + P4 treatment followed by LA significantly
decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify
gene expression, with the exception of IGFBP-5 that was significantly
increased. The GnRH analogues did not modify intracellular cAMP levels.
We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs
for SNX7. We conclude that GnRH analogues appear not to have major
direct effects on gene expression of human endometrial epithelial
cells in vitro.},
url = {http://molehr.oxfordjournals.org/cgi/content/abstract/16/5/347}
}
@ARTICLE{Zhang2008i,
author = {Zhang, Xiao and Chen, Jiamin and Radcliffe, Tom and LeBrun, Dave
P. and Tron, Victor A. and Feilotter, Harriet},
title = {An Array-Based Analysis of MicroRNA Expression Comparing Matched
Frozen and Formalin-Fixed Paraffin-Embedded Human Tissue Samples},
journal = {J. Mol. Diagn.},
year = {2008},
volume = {10},
pages = {513--519},
number = {6},
month = nov,
abstract = {MicroRNAs (miRNAs) are small, noncoding RNAs that suppress gene expression
at the posttranscriptional level via an antisense RNA-RNA interaction.
miRNAs used for array-based profiling are generally purified from
either snap-frozen or fresh samples. Because tissues found in most
pathology departments are available only in formalin-fixed and paraffin-embedded
(FFPE) states, we sought to evaluate miRNA derived from FFPE samples
for microarray analysis. In this study, miRNAs extracted from matched
snap-frozen and FFPE samples were profiled using the Agilent miRNA
array platform (Agilent, Santa Clara, CA). Each miRNA sample was
hybridized to arrays containing probes interrogating 470 human miRNAs.
Seven cases were compared in either duplicate or triplicate. Intrachip
and interchip analyses demonstrated that the processes of miRNA extraction,
labeling, and hybridization from both frozen and FFPE samples are
highly reproducible and add little variation to the results; technical
replicates showed high correlations with one another (Kendall tau,
0.722 to 0.853; Spearman rank correlation coefficient, 0.891 to 0.954).
Our results showed consistent high correlations between matched frozen
and FFPE samples (Kendall tau, 0.669 to 0.815; Spearman rank correlation
coefficient, 0.847 to 0.948), supporting the use of FFPE-derived
miRNAs for array-based, gene expression profiling.},
url = {http://jmd.amjpathol.org/cgi/content/abstract/10/6/513}
}
@ARTICLE{Zhang2009f,
author = {Zhang, Xichen and Hashemi, Shahreyar Shar and Yousefi, Morvarid and
Gao, Chunling and Sheng, Joy and Ni, Jinsong and Wang, Wan and Mason,
Jeffrey and Man, Yan-gao},
title = {Atypical E-cadherin expression in cell clusters overlying focally
disrupted mammary myoepithelial cell layers: Implications for tumor
cell motility and invasion},
journal = {Pathology - Research and Practice},
year = {2009},
volume = {205},
pages = {375--385},
number = {6},
month = jun,
abstract = {Our recent studies showed that cell clusters overlying focal myoepithelial
cell layer disruptions (FMCLD) had a significantly higher rate of
ER negativity, genetic instabilities, and expression of invasion-related
genes than adjacent cells within the same duct. This study attempted
to determine if these cells would show aberrant E-cadherin expression,
which imparts greater propensity for cell motility and invasion.
Consecutive sections from breast tumors with a high frequency of
FMCLD were double-immunostained for E-cadherin and a panel of related
markers. The E-cadherin mRNA levels in cells overlying FMCLD and
adjacent cells within the same duct were compared using real-time
PCR. Nearly all the cell clusters overlying FMCLD were strongly immunoreactive
for E-cadherin, whereas their adjacent counterparts within the same
duct were largely negative. Cell clusters overlying FMCLD were generally
arranged as tongue-like projections, "puncturing" deep into the stroma
or tube-like structures that often contained red blood cells. The
sub-cellular localization of E-cadherin in the above structures,
however, was primarily cytoplasmic. The mRNA level of E-cadherin
in cell clusters overlying FMCLD was significantly higher than that
in adjacent cells within the same duct. These findings suggest that
aberrant expression of E-cadherin may contribute to cell motility
and invasion.},
issn = {0344-0338},
keywords = {E-cadherin, Breast cancer invasion, Myoepithelial cell layer disruption,
Epithelial-stromal-interaction, Double immunohistochemistry},
url = {http://www.sciencedirect.com/science/article/B7GW5-4W4BMR2-1/2/5e92b06e50fb385dd2f956947b0bf988}
}
@ARTICLE{Zhang2005c,
author = {Zhang, Xingqi and Jafari, Nadereh and Barnes, Randall B. and Confino,
Edmond and Milad, Magdy and Kazer, Ralph R.},
title = {Studies of gene expression in human cumulus cells indicate pentraxin
3 as a possible marker for oocyte quality},
journal = {Fertility and Sterility},
year = {2005},
volume = {83},
pages = {1169--1179},
number = {4, Supplement 1},
month = apr,
abstract = {Objective To search for differentially expressed genes in cumulus
cells from two groups of oocytes with different developmental outcome
in vitro.Design Analyses of gene expression in human cumulus cells
from oocytes that failed to fertilize in vitro (group A) and those
that developed into normal-appearing embryos on day 3 (group B).Setting
University-based facilities for clinical service and research.Patient(s)
Women undergoing IVF treatment for infertility.Intervention(s) Cumulus
cells were collected from oocytes that were aspirated from ovarian
follicles for IVF. The oocytes were cultured individually for IVF
and embryo development. Total RNA was extracted from the cumulus
cells for gene expression analyses.Main Outcome Measure(s) General
gene expression profiles and relative abundance of pentraxin 3 (Ptx3)
mRNA.Result(s) DNA microarray analysis identified 160 genes, including
Ptx3, that were differentially expressed between cumulus cells in
group A and group B. Quantitative analysis confirmed that the relative
abundance of Ptx3 mRNA in cumulus cells was highly associated with
oocyte development.Conclusion(s) This study demonstrated that changes
in the expression levels of 160 genes, including particularly Ptx3,
in human cumulus cells may be indicative of the quality of their
enclosed oocyte.},
issn = {0015-0282},
keywords = {Cumulus cells, oocyte quality, gene expression, pentraxin 3},
url = {http://www.sciencedirect.com/science/article/B6T6K-4FXM4M1-G/2/505acfc8ed81c9d56919b12bc6193889}
}
@ARTICLE{Zhang2009g,
author = {Zhang, Xu and Lin, Peng and Zhu, Zhi-Hua and Long, Hao and Wen, Jing
and Yang, Hong and Zhang, Xing and Wang, Dao-Feng and Fu, Jian-Hua
and Fang, Yan and Rong, Tie-Hua},
title = {Expression profiles of early esophageal squamous cell carcinoma by
cDNA microarray},
journal = {Cancer Genetics and Cytogenetics},
year = {2009},
volume = {194},
pages = {23--29},
number = {1},
month = oct,
abstract = {An effective way to decrease the mortality rate in esophageal cancer
(EC) is to provide diagnosis and treatment for early EC patients.
Identification of molecular markers would be helpful for early diagnosis.
In this study, we obtained the gene expression profile of early esophageal
squamous cell carcinoma (ESCC) and further screened molecular markers
that might be useful in early diagnosis and treatment. RNA extracted
from EC cancer tissues and matched normal esophageal epithelium of
four EC patients were analyzed using whole-genome microarrays. Welch's
t-test was applied to normalized data to identify genes expressed
differently between cancer and normal tissues. Significantly differentially
expressed genes were classified according to gene ontology. Gene
mapping software was used to identify pathways involving the genes
that were significantly changed. Among the 54,613 gene transcripts
and variants analyzed, 367 were differentially expressed between
early ESCC and normal esophageal epithelium (Welch's t-test, P < 0.01).
Specifically, 104 genes were significantly upregulated and 263 were
downregulated in early ESCC, compared with normal esophageal epithelium.
Functional gene sets expressed differentially between ESCC cancer
and normal tissues included those involved in gene transcription,
cell proliferation, motility, apoptosis, and metabolism (specifically,
pathways of cell apoptosis, the cell cycle, G protein, and TGF-[beta]
signal transduction). We conclude that a large number of genes are
involved in the occurrence and development of early ESCC and take
part in various cell processes and pathways. The present findings
contribute theoretical information for further screening of genes
related to early ESCC.},
issn = {0165-4608},
url = {http://www.sciencedirect.com/science/article/B6T53-4X5JNTW-6/2/6269af4095951d18fe6b81008f90a772}
}
@ARTICLE{Zhang2011m,
author = {Zhang, Xiping and Patel, Samir P. and McCarthy, John J. and Rabchevsky,
Alexander G. and Goldhamer, David J. and Esser, Karyn A.},
title = {A non-canonical E-box within the MyoD core enhancer is necessary
for circadian expression in skeletal muscle},
journal = {Nucleic Acids Res.},
year = {2011},
pages = {gkr1297},
abstract = {The myogenic differentiation 1 (MyoD) gene is a master regulator of
myogenesis. We previously reported that the expression of MyoD mRNA
oscillates over 24 h in skeletal muscle and that the circadian clock
transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK
(circadian locomotor output cycles kaput), were bound to the core
enhancer (CE) of the MyoD gene in vivo. In this study, we provide
in vivo and in vitro evidence that the CE is necessary for circadian
expression of MyoD in adult muscle. Gel shift assays identified a
conserved non-canonical E-box within the CE that is bound by CLOCK
and BMAL1. Functional analysis revealed that this E-box was required
for full activation by BMAL1/CLOCK and for in vitro circadian oscillation.
Expression profiling of muscle of CEloxP/loxP mice found approximately
1300 genes mis-expressed relative to wild-type. Based on the informatics
results, we analyzed the respiratory function of mitochondria isolated
from wild-type and CEloxP/loxP mice. These assays determined that
State 5 respiration was significantly reduced in CEloxP/loxP muscle.
The results of this work identify a novel element in the MyoD enhancer
that confers circadian regulation to MyoD in skeletal muscle and
suggest that loss of circadian regulation leads to changes in myogenic
expression and downstream mitochondrial function.},
doi = {10.1093/nar/gkr1297},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/gkr1297v1.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/gkr1297v1}
}
@ARTICLE{Zhang2010b,
author = {Zhang, Xiaoling and Sebastiani, Paola and Liu, Gang and Schembri,
Frank and Zhang, Xiaohui and Dumas, Yves Martine and Langer, Erika
M. and Alekseyev, Yuriy and O'Connor, George T. and Brooks, Daniel
R. and Lenburg, Marc E. and Spira, Avrum},
title = {Similarities and differences between smoking-related gene expression
in nasal and bronchial epithelium},
journal = {Physiol Genomics},
year = {2010},
volume = {41},
pages = {1--8},
number = {1},
month = mar,
abstract = {Previous studies have shown that physiological responses to cigarette
smoke can be detected via bronchial airway epithelium gene expression
profiling and that heterogeneity in this gene expression response
to smoking is associated with lung cancer. In this study, we sought
to determine the similarity of the effects of tobacco smoke throughout
the respiratory tract by determining patterns of smoking-related
gene expression in paired nasal and bronchial epithelial brushings
collected from 14 healthy nonsmokers and 13 healthy current smokers.
Using whole genome expression arrays, we identified 119 genes whose
expression was affected by smoking similarly in both bronchial and
nasal epithelium, including genes related to detoxification, oxidative
stress, and wound healing. While the vast majority of smoking-related
gene expression changes occur in both bronchial and nasal epithelium,
we also identified 27 genes whose expression was affected by smoking
more dramatically in bronchial epithelium than nasal epithelium.
Both common and site-specific smoking-related gene expression profiles
were validated using independent microarray datasets. Differential
expression of select genes was also confirmed by RT-PCR. That smoking
induces largely similar gene expression changes in both nasal and
bronchial epithelium suggests that the consequences of cigarette
smoke exposure can be measured in tissues throughout the respiratory
tract. Our findings suggest that nasal epithelial gene expression
may serve as a relatively noninvasive surrogate to measure physiological
responses to cigarette smoke and/or other inhaled exposures in large-scale
epidemiological studies.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/41/1/1}
}
@ARTICLE{Zhang2008j,
author = {Zhang, Xun and Zarbl, Helmut},
title = {Chemopreventive Doses of Methylselenocysteine Alter Circadian Rhythm
in Rat Mammary Tissue},
journal = {Cancer Prevention Research},
year = {2008},
volume = {1},
pages = {119--127},
number = {2},
month = jul,
abstract = {It is known that organic forms of selenium inhibit chemically induced
rat mammary carcinogenesis, although the molecular basis remains
to be elucidated. To identify signaling pathways involved in carcinogenesis
that are also modulated by methylselenocysteine, we compared the
global gene expression profiles in mammary tissues from pubescent
female rats maintained on a selenium-supplemented (3 ppm) diet with
those on a standardized diet after N-nitroso-N-methylurea. Whereas
the selenium-enriched diet altered the steady-state levels of genes
involved in various cellular functions, the most dramatic effect
was the coordinated changes in the expression of multiple genes that
regulate circadian rhythm. Normal mammary tissue of rats fed a standardized
diet showed little circadian oscillation relative to liver tissue.
By contrast, mammary tissue of rats maintained on the selenium-enriched
diet showed a progressive, time-dependent increase in the expression
of circadian gene Per2 and circadian-regulated transcription factor
DBP. Our results further showed that the expression of Per2 and DBP
mRNAs was significantly decreased in mammary tumors arising in rats
on the selenium-enriched diet, but not in tumors of rats on the control
diet, suggesting that selenium-induced elevation in the expression
of circadian genes was incompatible with mammary carcinogenesis.
Given the previously reported role of Per2 as a tumor suppressor,
these observations suggest that Per2 is an important target of methylselenocysteine
during chemoprevention in N-nitroso-N-methylurea-induced rat mammary
carcinogenesis, and for the first time provide a link between chemoprevention
and circadian rhythm.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/1/2/119}
}
@ARTICLE{Zhang2006f,
author = {Zhang, Xue-Qian and Moorman, J. Randall and Ahlers, Belinda A. and
Carl, Lois L. and Lake, Douglas E. and Song, Jianliang and Mounsey,
J. Paul and Tucker, Amy L. and Chan, Yiu-mo and Rothblum, Lawrence
I. and Stahl, Richard C. and Carey, David J. and Cheung, Joseph Y.},
title = {Phospholemman overexpression inhibits Na+-K+-ATPase in adult rat
cardiac myocytes: relevance to decreased Na+ pump activity in postinfarction
myocytes},
journal = {J Appl Physiol},
year = {2006},
volume = {100},
pages = {212--220},
number = {1},
month = jan,
abstract = {Messenger RNA levels of phospholemman (PLM), a member of the FXYD
family of small single-span membrane proteins with putative ion-transport
regulatory properties, were increased in postmyocardial infarction
(MI) rat myocytes. We tested the hypothesis that the previously observed
reduction in Na+-K+-ATPase activity in MI rat myocytes was due to
PLM overexpression. In rat hearts harvested 3 and 7 days post-MI,
PLM protein expression was increased by two- and fourfold, respectively.
To simulate increased PLM expression post-MI, PLM was overexpressed
in normal adult rat myocytes by adenovirus-mediated gene transfer.
PLM overexpression did not affect the relative level of phosphorylation
on serine68 of PLM. Na+-K+-ATPase activity was measured as ouabain-sensitive
Na+-K+ pump current (Ip). Compared with control myocytes overexpressing
green fluorescent protein alone, Ip measured in myocytes overexpressing
PLM was significantly (P < 0.0001) lower at similar membrane voltages,
pipette Na+ ([Na+]pip) and extracellular K+ ([K+]o) concentrations.
From -70 to +60 mV, neither [Na+]pip nor [K+]o required to attain
half-maximal Ip was significantly different between control and PLM
myocytes. This phenotype of decreased Vmax without appreciable changes
in Km for Na+ and K+ in PLM-overexpressed myocytes was similar to
that observed in MI rat myocytes. Inhibition of Ip by PLM overexpression
was not due to decreased Na+-K+-ATPase expression because there were
no changes in either protein or messenger RNA levels of either {alpha}1-
or {alpha}2-isoforms of Na+-K+-ATPase. In native rat cardiac myocytes,
PLM coimmunoprecipitated with {alpha}-subunits of Na+-K+-ATPase.
Inhibition of Na+-K+-ATPase by PLM overexpression, in addition to
previously reported decrease in Na+-K+-ATPase expression, may explain
altered Vmax but not Km of Na+-K+-ATPase in postinfarction rat myocytes.},
url = {http://jap.physiology.org/cgi/content/abstract/100/1/212}
}
@ARTICLE{Zhang2008k,
author = {Zhang, Yonghua and Calvo, Ezequiel and Martel, Celine and Luu-The,
Van and Labrie, Fernand and Tchernof, Andre},
title = {Response of the adipose tissue transcriptome to dihydrotestosterone
in mice},
journal = {Physiol Genomics},
year = {2008},
volume = {35},
pages = {254--261},
number = {3},
month = nov,
abstract = {Androgens have been postulated to be important modulators of adipose
tissue metabolism and fat cell function. In the present study, we
investigated the response of male and female mice retroperitoneal
adipose tissue to the nonaromatizable androgen dihydrotestosterone
(DHT). Adipose tissue samples were obtained in gonadectomized animals
treated with vehicle (control group), or injected with 0.1 mg DHT
1, 3, 6, 12, 18, and 24 h prior to necropsy. Fourteen animals were
pooled at each time point (total 196 animals). Transcripts that were
significantly modulated were considered as androgen-responsive genes.
Quantitative real-time RT-PCR was used to confirm results from the
microarray analysis in a subset of 46 probe sets in male mice and
98 probe sets in female mice. Considering peak time vs. control,
we confirmed 74.0 and 63.3% of the modulated genes by PCR in males
and females, respectively. Four genes were significantly stimulated
in a similar manner by DHT in both sexes, namely metallothionein
1, growth arrest and DNA-damage-inducible 45 gamma, cyclin-dependent
kinase inhibitor 1A, and fk506-binding protein 5. All these genes
appear to be involved in the regulation of adipocyte differentiation/proliferation
and adipogenesis. In conclusion, this study, which evaluated the
acute transcriptome response of adipose tissue to DHT in male and
female mice, suggests that DHT consistently modulates genes involved
in the regulation of adipogenesis in retroperitoneal adipose tissue
of both male and female animals.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/35/3/254}
}
@ARTICLE{Zhang2005d,
author = {Zhang, Yanli and James, Michael and Middleton, Frank A. and Davis,
Richard L.},
title = {Transcriptional analysis of multiple brain regions in Parkinson's
disease supports the involvement of specific protein processing,
energy metabolism, and signaling pathways, and suggests novel disease
mechanisms},
journal = {Am. J. Med. Genet.},
year = {2005},
volume = {137B},
pages = {5--16},
number = {1},
abstract = {Abstract 10.1002/ajmg.b.30195.abs In both genetic and idiopathic forms
of Parkinson's disease (PD), considerable evidence supports the involvement
of α-synuclein, electron transport chain complex I, protein aggregation,
and the ubiquitin-proteasome system. To investigate alterations in
the transcription of genes that comprise these pathways, we performed
gene expression profiling and functional gene group analysis of three
brain regions (the substantia nigra, putamen, and area 9) in postmortem
tissue from matched groups of PD or control subjects (n = 15/group).
Verification of selected changes was performed using RT-PCR, and
visualization of selected changes in expression was accomplished
using in situ hybridization (ISH). Our results provide strong support
for the impairment of multiple electron transport chain complexes
and the ubiquitin-proteasomal system in PD, along with a robust induction
of heat shock proteins and some anti-apoptotic gene groups. Several
novel gene and gene group findings were also obtained that offer
new insight into the pathogenesis and potential treatment of PD.
© 2005 Wiley-Liss, Inc.},
issn = {1552-485X},
keywords = {microarray, RNA, postmortem, basal ganglia, neurodegeneration, cerebral
cortex},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ajmg.b.30195}
}
@ARTICLE{Zhang2011c,
author = {Zhang, Yingbiao and Li, Wenzhe and Chi, Yan and Wang, Renjun and
Wang, Dan and Zhang, Fan and Liu, Zhe and Matsuura, Eiji and Liu,
Qingping},
title = {Recombinant domain V of {beta}2-glycoprotein I inhibits the formation
of a 7-ketocholesteryl-9-carboxynonanoate and {beta}2-glycoprotein
I complex},
journal = {J. Biochem.},
year = {2011},
volume = {149},
pages = {35--42},
number = {1},
month = jan,
abstract = {Our prior study has been reported the formation of the oxidized low-density
lipoprotein (oxLDL)/{beta}2-glycoproteinI ({beta}2-GPI)/autoantibody
complex facilitated the antiphospholipid syndrome (APS) process.
The domain V of {beta}2-GPI binds to the negatively charged molecules,
e.g. 7-ketochoresteryl-9-caboxynonanoate (oxLig-1) derived from the
oxLDL and mediates the interaction between oxLDL and {beta}2-GPI.
In the present study, the oxLig-1/{beta}2-GPI/anti-{beta}2-GPI Ab
(WB-CAL-1) model was established. The recombinant domain V of {beta}2-GPI
(r{beta}2-GPI DV) expressed in Escherichia coli competitively inhibits
the interaction between {beta}2-GPI and oxLig-1 in the enzyme-linked
immunoassay. Moreover, the r{beta}2-GPI DV significantly inhibits
the formation of the oxLig-1/{beta}2-GPI/autoantibody complex in
an APS patient. The present work suggests a novel possibility that
r{beta}2-GPI DV could be used to inhibit the formation of oxLDL/{beta}2-GPI/autoantibody
complex, and give us a hint for the development of new therapeutic
strategies to prevent the APS process.},
comment = {10.1093/jb/mvq111},
url = {http://jb.oxfordjournals.org/cgi/content/abstract/149/1/35}
}
@ARTICLE{Zhang2010d,
author = {Zhang, Y. and Liu, Y. and Xu, J. and Nimri, N. and Wildsoet, C. F.},
title = {Microarray Analysis of RPE Gene Expression in Chicks During Long-term
Imposed Myopic Defocus},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {3680--},
number = {5},
month = apr,
abstract = {PurposeThis study examined the role of the retinal pigment epithelium
(RPE) in transferring ocular growth signals from retina to sclera
during the development of lens-induced myopia and possible secondary
effects of myopia on RPE function. MethodsTo induce myopia, 4 White-Leghorn
chicks wore monocular -15D lenses from 10-days of age for 38 days.
Retinoscopy and high-frequency A-scan ultrasonography were used to
monitor refractive errors (RE) and axial ocular dimensions of both
treated and untreated fellow eyes, which served as controls. Chicks
were then euthanized with euthasol, eyes enucleated, RPE isolated
and RNA extracted. After verification of its quality in 2 ways, by
spectrophotometry and using an Agilent 2100 bioanalyzer with an RNA
6000 Pico Chip Kit, RNA was subjected to cDNA synthesis, in vitro
transcription and labeling. The labeled cRNA product was then cleaned
up, quantified, fragmented, and hybridized onto Affymetrix GeneChip
Chicken Genome Arrays. Microarray data were analyzed using BioConductor
package. Expression patterns for RPE from myopic and fellow eyes
were compared. ResultsSignificant myopia and axial length (AL) increases
were recorded in treated eyes compared to their fellows after 38
days of treatment (RE: -13.00{+/-}0.46 cf. +4.06{+/-}0.33D; AL: 14.65{+/-}0.24
cf.12.67{+/-}0.19mm). Eight hundred and fifty-two transcripts were
up- or down-regulated in myopic compared to fellow eyes, by at least
1.5-fold (p<0.05). Up-regulated growth factors and receptors included
BMP2, BMP7, TGFB2, FGF1, PDGFA, FIGF, FGFR2, PDGFRA, and KDR. However,
BMP receptors, TGF-{beta} receptors and Smad proteins were not differentially
expressed. Four neurotransmitter receptors (DRD4, GRM3, GRIN2A, GRIA3),
a water channel (AQP4), a transporter (CRABP1), 2 peptidases (MMP2,
PLAU), and a tight junction protein (CLDN2) also were up-regulated,
while the neurotransmitter receptor, GABBR2, was down-regulated.
ConclusionsDifferential expression was observed in a range of genes
that could plausibly be involved in ocular growth regulation, based
on their known actions in other tissues, although functional changes
in RPE secondary to myopic growth may underlie changes in some affected
genes, e.g. tight junctions. Gene expression changes involving the
protein but not its receptor are compatible with a model of secretion
from RPE to modulate the function or growth of adjacent tissues,
while cases involving both the protein and related receptor are suggestive
of complex roles, including constitutive activity.},
url = {http://abstracts.iovs.org/cgi/content/abstract/51/5/3680}
}
@ARTICLE{Zhang2011i,
author = {Zhang, Yinghui and Moerkens, Marja and Ramaiahgari, Sreenivasa and
de Bont, Hans and Price, Leo and Meerman, John and van de Water,
Bob},
title = {Elevated insulin-like growth factor 1 receptor signaling induces
antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling
routes},
journal = {Breast Cancer Research},
year = {2011},
volume = {13},
pages = {R52},
number = {3},
abstract = {INTRODUCTION:Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R)
is phosphorylated in all breast cancer subtypes. Past findings have
shown that IGF-1R mediates antiestrogen resistance through cross-talk
with estrogen receptor (ER) signaling and via its action upstream
of the epidermal growth factor receptor and human epidermal growth
factor receptor 2. Yet, the direct role of IGF-1R signaling itself
in antiestrogen resistance remains obscure. In the present study,
we sought to elucidate whether antiestrogen resistance is induced
directly by IGF-1R signaling in response to its ligand IGF-1 stimulation.METHODS:A
breast cancer cell line ectopically expressing human wild-type IGF-1R,
MCF7/IGF-1R, was established by retroviral transduction and colony
selection. Cellular antiestrogen sensitivity was evaluated under
estrogen-depleted two-dimensional (2D) and 3D culture conditions.
Functional activities of the key IGF-1R signaling components in antiestrogen
resistance were assessed by specific kinase inhibitor compounds and
small interfering RNA.RESULTS:Ectopic expression of IGF-1R in ER-positive
MCF7 human breast cancer cells enhanced IGF-1R tyrosine kinase signaling
in response to IGF-1 ligand stimulation. The elevated IGF-1R signaling
rendered MCF7/IGF-1R cells highly resistant to the antiestrogens
tamoxifen and fulvestrant. This antiestrogen-resistant phenotype
involved mitogen-activated protein kinase/extracellular signal-regulated
kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase
B pathways downstream of the IGF-1R signaling hub and was independent
of ER signaling. Intriguingly, a MAPK/ERK-dependent agonistic behavior
of tamoxifen at low doses was triggered in the presence of IGF-1,
showing a mild promitogenic effect and increasing ER transcriptional
activity.CONCLUSIONS:Our data provide evidence that the IGF-1/IGF-1R
signaling axis may play a causal role in antiestrogen resistance
of breast cancer cells, despite continuous suppression of ER transcriptional
function by antiestrogens.},
doi = {10.1186/bcr2883},
issn = {1465-5411},
pubmedid = {21595894},
url = {http://breast-cancer-research.com/content/13/3/R52}
}
@ARTICLE{Zhang2009h,
author = {Zhang, Yonghua and Nadeau, Mélanie and Faucher, Frédérick and Lescelleur,
Odette and Biron, Simon and Daris, Marleen and Rhéaume, Caroline
and Luu-The, Van and Tchernof, André},
title = {Progesterone metabolism in adipose cells},
journal = {Molecular and Cellular Endocrinology},
year = {2009},
volume = {298},
pages = {76--83},
number = {1-2},
month = jan,
abstract = {The aim of the present study was to investigate pathways of progesterone
metabolism in human adipose cells. Adipose tissue samples from the
omental (OM) and subcutaneous (SC) fat compartments were surgically
obtained in women. In isolated mature adipocytes, progesterone was
converted to 20[alpha]-hydroxyprogesterone as the main metabolite,
most likely through the activity of aldo-keto reductases 1C1, 2 and
3 (20[alpha]-HSD, 3[alpha]-HSD type 3 and 17[beta]-HSD type 5, respectively).
In cultured preadipocytes, progesterone was converted to several
metabolites identified using bidimensional thin layer chromatography,
with or without the dual inhibitor of 5[alpha]-reductase type 1 and
2 (17[beta]-N,N-diethylcarbamoyl-4-methyl-4-aza-5[alpha]-androstan-3-one
(4-MA)). Major metabolites identified in OM and SC preadipocytes
which were incubated for 24 h with 14C-labelled progesterone were
20[alpha]-hydroxyprogesterone, 5[alpha]-pregnane-3[alpha]/[beta]-ol-20-one,
5[alpha]- and 5[beta]-pregnanedione, 5[alpha]- and 5[beta]-pregnane-20[alpha]-ol-3-one,
5[alpha]-pregnane-3[alpha]/[beta]-ol-20-one and 5[beta]-pregnane-3[alpha]/[beta]-20[alpha]-diol.
Induction of preadipocyte differentiation increased expression levels
of AKR1C1 and modified the pattern of progesterone metabolism substantially,
leaving 20[alpha]-hydroxyprogesterone as the main metabolite generated.
On the other hand, progesterone itself showed no consistent effect
on adipocyte differentiation. In conclusion, preadipocytes and lipid-storing,
mature adipocytes efficiently generate progesterone metabolites in
women, which is consistent with rather modest effects progesterone
on abdominal fat cell differentiation.},
issn = {0303-7207},
keywords = {20[alpha]-Hydroxyprogesterone, Adipocyte, Omental, Differentiation,
Aldo-keto reductases 1C},
url = {http://www.sciencedirect.com/science/article/B6T3G-4TP49RX-1/2/0141089b0bd80483271b38a429436bf1}
}
@ARTICLE{Zhang2006g,
author = {Zhang, Yueting and Taveggia, Carla and Melendez-Vasquez, Carmen and
Einheber, Steven and Raine, Cedric S. and Salzer, James L. and Brosnan,
Celia F. and John, Gareth R.},
title = {Interleukin-11 Potentiates Oligodendrocyte Survival and Maturation,
and Myelin Formation},
journal = {J. Neurosci.},
year = {2006},
volume = {26},
pages = {12174--12185},
number = {47},
month = nov,
abstract = {Mechanisms that regulate oligodendrocyte survival and myelin formation
are an intense focus of research into myelin repair in the lesions
of multiple sclerosis (MS). Although demyelination and oligodendrocyte
loss are pathological hallmarks of the disease, increased oligodendrocyte
numbers and remyelination are frequently observed in early lesions,
but these diminish as the disease course progresses. In the current
study, we used a microarray-based approach to investigate genes regulating
repair in MS lesions, and identified interleukin-11 (IL-11) as an
astrocyte-derived factor that potentiates oligodendrocyte survival
and maturation, and myelin formation. IL-11 was induced in human
astrocyte cultures by the cytokines IL-1[beta] and TGF[beta]1, which
are both prominently expressed in MS plaques. In MS tissue samples,
IL-11 was expressed by reactive astrocytes, with expression particularly
localized at the myelinated border of both active and silent lesions.
Its receptor, IL-11R{alpha}, was expressed by oligodendrocytes. In
experiments in human cultures in vitro, IL-11R{alpha} localized to
immature oligodendrocytes, and its expression decreased during maturation.
In cultures treated with IL-11, we observed a significant increase
in oligodendrocyte number, and this was associated with enhanced
oligodendrocyte survival and maturation. Importantly, we also found
that IL-11 treatment was associated with significantly increased
myelin formation in rodent CNS cocultures. These data are the first
to implicate IL-11 in oligodendrocyte viability, maturation, and
myelination. We suggest that this pathway may represent a potential
therapeutic target for oligodendrocyte protection and remyelination
in MS.},
url = {http://www.jneurosci.org/cgi/content/abstract/26/47/12174}
}
@ARTICLE{Zhang2009i,
author = {Zhang, Yan and Wong, Jasmine and Klinger, Mark and Tran, Mary T.
and Shannon, Kevin M. and Killeen, Nigel},
title = {Mll5 contributes to hematopoietic stem cell fitness and homeostasis},
journal = {Blood},
year = {2009},
volume = {113},
pages = {1455--1463},
number = {7},
month = feb,
abstract = {MLL5 is a novel trithorax group gene and a candidate tumor suppressor
gene located within a 2.5-Mb interval of chromosome band 7q22 that
frequently is deleted in human myeloid malignancy. Here we show that
inactivation of the Mll5 gene in mice results in a 30% reduction
in the average representation of hematopoietic stem cells and in
functional impairment of long-term hematopoietic repopulation potential
under competitive conditions. Bone marrow cells from Mll5-deficient
mice were defective in spleen colony-forming assays, and the mutant
mice showed enhanced susceptibility to 5-fluorouracil-induced myelosuppression.
Heterozygous and homozygous Mll5 mutant mice did not spontaneously
develop hematologic cancers, and loss of Mll5 did not alter the phenotype
of a fatal myeloproliferative disorder induced by oncogenic Kras
in vivo. Collectively, the data reveal an important role for Mll5
in HSC homeostasis and provide a basis for further studies to explore
its role in leukemogenesis.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/7/1455}
}
@ARTICLE{Zhang2009j,
author = {Zhang, Ying V. and Cheong, Janice and Ciapurin, Nichita and McDermitt,
David J. and Tumbar, Tudorita},
title = {Distinct Self-Renewal and Differentiation Phases in the Niche of
Infrequently Dividing Hair Follicle Stem Cells},
journal = {Cell Stem Cell},
year = {2009},
volume = {5},
pages = {267--278},
number = {3},
month = sep,
abstract = {Summary In homeostasis of adult vertebrate tissues, stem cells are
thought to self-renew by infrequent and asymmetric divisions that
generate another stem cell daughter and a progenitor daughter cell
committed to differentiate. This model is based largely on in vivo
invertebrate or in vitro mammal studies. Here, we examine the dynamic
behavior of adult hair follicle stem cells in their normal setting
by employing mice with repressible H2B-GFP expression to track cell
divisions and Cre-inducible mice to perform long-term single-cell
lineage tracing. We provide direct evidence for the infrequent stem
cell division model in intact tissue. Moreover, we find that differentiation
of progenitor cells occurs at different times and tissue locations
than self-renewal of stem cells. Distinct fates of differentiation
or self-renewal are assigned to individual cells in a temporal-spatial
manner. We propose that large clusters of tissue stem cells behave
as populations whose maintenance involves unidirectional daughter-cell-fate
decisions.},
issn = {1934-5909},
keywords = {STEMCELL},
url = {http://www.sciencedirect.com/science/article/B8G3V-4WXYTRF-1/2/34ebab4ceba3485b2425f7cd9ced5a9b}
}
@ARTICLE{Zhang2007b,
author = {Zhang, Yong-Mei and Chohnan, Shigeru and Virga, Kristopher G. and
Stevens, Robert D. and Ilkayeva, Olga R. and Wenner, Brett R. and
Bain, James R. and Newgard, Christopher B. and Lee, Richard E. and
Rock, Charles O. and Jackowski, Suzanne},
title = {Chemical Knockout of Pantothenate Kinase Reveals the Metabolic and
Genetic Program Responsible for Hepatic Coenzyme A Homeostasis},
journal = {Chemistry \& Biology},
year = {2007},
volume = {14},
pages = {291--302},
number = {3},
month = mar,
abstract = {Summary Coenzyme A (CoA) is the major acyl group carrier in intermediary
metabolism. Hopantenate (HoPan), a competitive inhibitor of the pantothenate
kinases, was used to chemically antagonize CoA biosynthesis. HoPan
dramatically reduced liver CoA and mice developed severe hypoglycemia.
Insulin was reduced, glucagon and corticosterone were elevated, and
fasting accelerated hypoglycemia. Metabolic profiling revealed a
large increase in acylcarnitines, illustrating the role of carnitine
in buffering acyl groups to maintain the nonesterified CoASH level.
HoPan triggered significant changes in hepatic gene expression that
substantially increased the thioesterases, which liberate CoASH from
acyl-CoA, and increased pyruvate dehydrogenase kinase 1, which prevents
the conversion of CoASH to acetyl-CoA. These results identify the
metabolic rearrangements that maintain the CoASH pool which is critical
to mitochondrial functions, including gluconeogenesis, fatty acid
oxidation, and the tricarboxylic acid and urea cycles.},
issn = {1074-5521},
keywords = {CHEMBIOL, SIGNALING, DNA},
url = {http://www.sciencedirect.com/science/article/B6VRP-4NB3J16-B/2/aa78b71fee3e7be59e23706f53aa3da7}
}
@ARTICLE{Zhang2007c,
author = {Zhang, Yong-Mei and Zhu, Kun and Frank, Matthew W. and Rock, Charles
O.},
title = {A Pseudomonas aeruginosa transcription factor that senses fatty acid
structure},
journal = {Molecular Microbiology},
year = {2007},
volume = {66},
pages = {622--632},
number = {3},
abstract = {Summary Cells regulate their membrane phospholipid biophysical properties
by the co-ordinated synthesis of saturated and unsaturated fatty
acids. In bacteria, unsaturated fatty acids are produced by the de
novo fatty acid biosynthetic pathway anaerobically, or by oxidative
desaturation of the existing fatty acids catalysed by desaturases.
A transcriptional repressor in Pseudomonas aeruginosa, DesT (PA4890),
regulates the expression of an acyl-CoA desaturase operon (desCB,
PA4889 and PA4888). The desCB operon is located adjacent to desT
and is transcribed in the opposite direction. The expression level
of desCB is strongly and selectively upregulated in a ΔdesT-deletion
strain. Both electrophoresis mobility shift assay and DNase I footprinting
analysis demonstrated the existence of two DesT binding sites in
the desT–desCB promoter region, P1 and P2. The binding of purified
DesT to P2 was enhanced by unsaturated acyl-CoAs, whereas saturated
acyl-CoAs prevented DesT interaction with P2. The biological importance
of this interaction was verified by the upregulation of desCB and
desT in cells grown in the presence of stearate and their repression
when oleate was present. This unique ligand selectivity allows DesT
to sense the physical properties of the cellular acyl-CoA pool and
modulate the expression of the acyl-CoA Δ9-desaturase system to
adjust fatty acid desaturation activity accordingly.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2007.05934.x}
}
@ARTICLE{Zhang2009k,
author = {Zhang, Yu-Qiu and Guo, Ning and Peng, Guangdun and Han, Mei and Raincrow,
Jeremy and Chiu, Chi-hua and Coolen, Lique M. and Wenthold, Robert
J. and Zhao, Zhi-Qi and Jing, Naihe and Yu, Lei},
title = {Role of SIP30 in the development and maintenance of peripheral nerve
injury-induced neuropathic pain},
journal = {Pain},
year = {2009},
volume = {146},
pages = {130--140},
number = {1-2},
month = nov,
abstract = {Using the chronic constriction injury (CCI) model of neuropathic pain,
we profiled gene expression in the rat spinal cord, and identified
SIP30 as a gene whose expression was elevated after CCI. SIP30 was
previously shown to interact with SNAP25, but whose function was
otherwise unknown. We now show that in the spinal cord, SIP30 was
present in the dorsal horn laminae where the peripheral nociceptive
inputs first synapse, co-localizing with nociception-related neuropeptides
CGRP and substance P. With the onset of neuropathic pain after CCI
surgery, SIP30 mRNA and protein levels increased in the ipsilateral
side of the spinal cord, suggesting a potential association between
SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited
by intrathecal antisense oligonucleotide administration, neuropathic
pain was attenuated. This neuropathic pain-reducing effect was observed
both during neuropathic pain onset following CCI, and after neuropathic
pain was fully established, implicating SIP30 involvement in the
development and maintenance phases of neuropathic pain. Using a secretion
assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of
synaptic vesicles available for exocytosis, pointing to a potential
function for SIP30. These results suggest a role of SIP30 in the
development and maintenance of peripheral nerve injury-induced neuropathic
pain.},
issn = {0304-3959},
keywords = {SIP30, Neuropathic pain, Chronic constriction injury, Spinal cord,
Intrathecal, Dorsal horn},
url = {http://www.sciencedirect.com/science/article/B6T0K-4X6VB1X-1/2/7f8cc763f592d2609a21ca74c99a4131}
}
@ARTICLE{Zhang2010c,
author = {Zhang, Zhiyong and Lowry, Stephen F. and Guarente, Leonard and Haimovich,
Beatrice},
title = {Roles of SIRT1 in the Acute and Restorative Phases following Induction
of Inflammation},
journal = {J. Biol. Chem.},
year = {2010},
volume = {285},
pages = {41391--41401},
number = {53},
month = dec,
abstract = {Endotoxin is a potent inducer of systemic inflammatory responses in
human and rodents. Here, we show that in vivo endotoxin triggers
a rapid and transient decline in ATP concentration in human peripheral
blood leukocytes and murine peripheral blood leukocytes and liver,
which is associated with a brief increase in expression of the autophagy
indicator LC3-II. In both of these tissues, the ATP concentration
reaches a nadir, and autophagy is induced between 2 and 4 h post-endotoxin
infusion, and homeostasis is restored within 12 h. Mouse liver SIRT1
and AMP-activated protein kinase (AMPK) protein expression levels
decline precipitously within 10 min and remain below detection levels
for up to 12 h post-endotoxin administration. In marked contrast,
the expression of HIF-1{alpha} is induced within 90 min and remains
elevated for up to 12 h. The ATP recovery is delayed, and the increases
in both HIF-1{alpha} expression and autophagy are prolonged in endotoxin-challenged
SIRT1 liver knock-out mice. Resveratrol prevents the decline in ATP
concentration and SIRT1 expression, as well as the increase in HIF-1{alpha}
expression and autophagy in liver of endotoxin-challenged wild type
mice but not in SIRT1 liver knock-out mice. These results provide
novel insight into the state of both cellular bioenergetics and metabolic
networks during the acute phase of systemic inflammation and suggest
a role for SIRT1 in acute metabolic decline, as well as the restoration
of metabolic homeostasis during an inflammatory challenge.},
comment = {10.1074/jbc.M110.174482},
url = {http://www.jbc.org/cgi/content/abstract/285/53/41391}
}
@ARTICLE{Zhang2004d,
author = {Zhang, Zhi and Stanley, Samuel L.},
title = {Stereotypic and specific elements of the human colonic response to
Entamoeba histolytica and Shigella flexneri},
journal = {Cellular Microbiology},
year = {2004},
volume = {6},
pages = {535--554},
number = {6},
abstract = {Summary The clinical presentations of bacillary dysentery caused by
shigella, and amoebic dysentery caused by the protozoan parasite
Entamoeba histolytica, can be indistinguishable, with both organisms
causing colonic mucosal damage and ulceration. However, the two organisms
are quite distinct, and have very different pathogenic mechanisms.
This raises the fundamental question of whether the similar clinical
manifestations reflect a stereotypic response of the human gut to
mucosal injury, or whether there are differences at the molecular
level in the host response to individual gut pathogens. To characterize
the human colonic response to each pathogen at the molecular level,
we measured the differential transcription of nearly 40Â 000 human
genes in sections of human colonic xenografts obtained 4 and 24Â h
following infection with Shigella flexneri or E. histolytica. Our
results indicate that much of the human colonic response to these
two pathogens is stereotypic, with increased expression of genes
activated in cells undergoing stress and/or hypoxic responses, genes
encoding cytokines, chemokines, and mediators that are involved in
immune and inflammatory responses, and genes encoding proteins involved
in responses to tissue injury and in tissue repair. The responses
to amoeba and Shigella were not identical however, and we found unique
elements in each response that may provide new insights into the
distinct pathogenic mechanisms of E. histolytica and S. flexneri.},
issn = {1462-5822},
publisher = {Blackwell Science Ltd},
url = {http://dx.doi.org/10.1111/j.1462-5822.2004.00381.x}
}
@ARTICLE{Zhang2011b,
author = {Zhang, Zhaolin and Xu, Jingjing and Sheng, Zhentao and Sui, Yipeng
and Palli, Subba R.},
title = {Steroid Receptor Co-activator Is Required for Juvenile Hormone Signal
Transduction through a bHLH-PAS Transcription Factor, Methoprene
Tolerant},
journal = {J. Biol. Chem.},
year = {2011},
volume = {286},
pages = {8437--8447},
number = {10},
month = mar,
abstract = {Metamorphosis in insects is regulated by juvenile hormone (JH) and
ecdysteroids. The mechanism of 20-hydroxyecdysone (20E), but not
of JH action, is well understood. A basic helix-loop-helix (bHLH)-Per-Arnt-Sim
(PAS) family member, methoprene tolerant (Met), plays an important
role in JH action. Microarray analysis and RNA interference (RNAi)
were used to identify 69 genes that require Met for their hydroprene-regulated
expression in the red flour beetle, Tribolium castaneum. Quantitative
real time PCR analysis confirmed microarray data for 13 of the 16
hydroprene-response genes tested. The members of the bHLH-PAS family
often function as heterodimers to regulate gene expression and Met
is a member of this family. To determine whether other members of
the bHLH-PAS family are required for the expression of JH-response
genes, we employed RNAi to knockdown the expression of all 11 members
of the bHLH-PAS family and studied the expression of JH-response
genes in RNAi insects. These studies showed that besides Met, another
member of this family, steroid receptor co-activator (SRC) is required
for the expression of 15 JH-response genes tested. Moreover, studies
in JH responsive Aag-2 cells revealed that Aedes aegypti homologues
of both Met and SRC are required for the expression of the JH-response
gene, kr-h1, and SRC is required for expression of ecdysone-response
genes. These data suggest the steroid receptor co-activator plays
key roles in both JH and 20E action suggesting that this may be an
important molecule that mediates cross-talk between JH and 20E to
prevent metamorphosis.},
comment = {10.1074/jbc.M110.191684},
url = {http://www.jbc.org/cgi/content/abstract/286/10/8437}
}
@ARTICLE{Zhao2005,
author = {Zhao, Aiping and Morimoto, Motoko and Dawson, Harry and Elfrey, Justin
E. and Madden, Kathleen B. and Gause, William C. and Min, Booki and
Finkelman, Fred D. and Urban, Joseph F., Jr and Shea-Donohue, Terez},
title = {Immune Regulation of Protease-Activated Receptor-1 Expression in
Murine Small Intestine during Nippostrongylus brasiliensis Infection},
journal = {J. Immunol.},
year = {2005},
volume = {175},
pages = {2563--2569},
number = {4},
month = aug,
abstract = {Infection with gastrointestinal nematodes exerts profound effects
on both immune and physiological responses of the host. Helminth
infection induces a hypercontractility of intestinal smooth muscle
that is dependent on the Th2 cytokines, IL-4 and IL-13, and may contribute
to worm expulsion. Protease-activated receptors (PARs) are expressed
throughout the gut, and activation of PAR-1 was observed in asthma,
a Th2-driven pathology. In the current study we investigated the
physiologic and immunologic regulation of PAR-1 in the murine small
intestine, specifically 1) the effect of PAR-1 agonists on small
intestinal smooth muscle contractility, 2) the effects of Nippostrongylus
brasiliensis infection on PAR-1 responses, 3) the roles of IL-13
and IL-4 in N. brasiliensis infection-induced alterations in PAR-1
responses, and 4) the STAT6 dependence of these responses. We demonstrate
that PAR-1 activation induces contraction of murine intestinal smooth
muscle that is enhanced during helminth infection. This hypercontractility
is associated with an elevated expression of PAR-1 mRNA and protein.
N. brasiliensis-induced changes in PAR-1 function and expression
were seen in IL-4-deficient mice, but not in IL-13- or STAT6-deficient
mice, indicating the dependence of IL-13 on the STAT6 signaling pathway
independent of IL-4.},
url = {http://www.jimmunol.org/cgi/content/abstract/175/4/2563}
}
@ARTICLE{Zhao2008,
author = {Zhao, Aiping and Urban Jr, Joseph F. and Anthony, Robert M. and Sun,
Rex and Stiltz, Jennifer and van Rooijen, Nico and Wynn, Thomas A.
and Gause, William C. and Shea-Donohue, Terez},
title = {Th2 Cytokine-Induced Alterations in Intestinal Smooth Muscle Function
Depend on Alternatively Activated Macrophages},
journal = {Gastroenterology},
year = {2008},
volume = {135},
pages = {217--225.e1},
number = {1},
month = jul,
abstract = {Background & Aims: Enteric nematode infection induces a strong type
2 T helper cell (Th2) cytokine response characterized by increased
infiltration of various immune cells, including macrophages. The
role of these immune cells in host defense against nematode infection
remains poorly defined. The present study investigated the role of
macrophages and the arginase pathway in nematode-induced changes
in intestinal smooth muscle function and worm expulsion. Methods:
Mice were infected with Nippostrongylus brasiliensis and treated
with clodronate-containing liposome to deplete macrophages or given
S-(2-boronoethyl)-I-cysteine in drinking water to inhibit arginase
activity. Segments of intestinal smooth muscle were suspended in
organ baths to determine responses to acetylcholine, 5-hydroxytryptamine,
or nerve stimulation. The phenotype of macrophages was monitored
by measuring mRNA expression of the specific molecular markers by
real-time polymerase chain reaction or viewed by immunofluorescence
staining. Results: Infection increased the infiltration of macrophages
and up-regulation alternatively activated macrophage markers by a
mechanism dependent on interleukin-4 (IL-4) or interleukin-13 (IL-13)
activation of signal transducer and activator of transcription 6.
Elimination of alternatively activated macrophages blocked smooth
muscle hypercontractility and the increased smooth muscle thickness,
and impaired worm expulsion. In addition, specific inhibition of
arginase activity interfered with smooth muscle contractility, but
only partially affected the protective immunity of the host. Conclusions:
These data show that the phenotype of macrophages is determined by
the local immune environment and that alternatively activated macrophages
play a major role in the effects of Th2 cytokines, IL-4 and IL-13,
on intestinal smooth muscle function.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4S6P1XW-3/2/829d7a1fdef5b1a5db3794db0b8c24a3}
}
@ARTICLE{Zhao2006,
author = {Zhao, Aiping and Urban Jr, Joseph F. and Morimoto, Motoko and Elfrey,
Justin E. and Madden, Kathleen B. and Finkelman, Fred D. and Shea-Donohue,
Terez},
title = {Contribution of 5-HT2A Receptor in Nematode Infection-Induced Murine
Intestinal Smooth Muscle Hypercontractility},
journal = {Gastroenterology},
year = {2006},
volume = {131},
pages = {568--578},
number = {2},
month = aug,
abstract = {Background & Aims: Enteric nematode infection induces a smooth muscle
hypercontractility that depends on interleukin (IL)-4 and IL-13 activation
of the signal transducer and activator of transcription (STAT) 6.
Serotonin (5-HT) is involved in the physiologic regulation of gut
function. The present study investigated the contribution of 5-HT
and its receptors in nematode-induced intestinal smooth muscle hypercontractility.
Methods: Mice were infected with Nippostrongylus brasiliensis (N
brasiliensis) or Heligmosomoides polygyrus (H polygyrus) or injected
intravenously with IL-13. Segments of jejunum were suspended in organ
baths, and smooth muscle responses to 5-HT were determined in the
presence or absence of specific 5-HT antagonists. IL-4, IL-13, and
5-HT receptor messenger RNA expressions were determined by real-time
quantitative polymerase chain reaction. Results: 5-HT evoked a modest
contraction of smooth muscle in wild-type (WT) mice that was unaltered
by the 5-HT2A antagonist ketanserin. N brasiliensis infection induced
a smooth muscle hypercontractility to 5-HT that was abolished by
5-HT2A antagonists but not by other 5-HT antagonists. Infection-induced
up-regulation of 5-HT2A expression was correlated with the smooth
muscle hypercontractility to 5-HT. The infection-induced up-regulation
of 5-HT2A in WT mice was observed also in IL-4-/- mice but was not
seen in IL-13-/- or STAT6-/- mice. In addition, smooth muscle responses
to 5-HT and 5-HT2A expression in WT mice were also enhanced by IL-13
or H polygyrus infection. Conclusions: These data show that 5-HT2A
is one of the molecules downstream from STAT6 activation that mediates
changes in smooth muscle function. 5-HT2A represents a novel therapeutic
target for modulating immune-mediated effects on intestinal motility.},
issn = {0016-5085},
url = {http://www.sciencedirect.com/science/article/B6WFX-4KJKXVY-1G/2/8ee38024575e479b42edc7d8f1f39b4a}
}
@ARTICLE{Zhao2009,
author = {Zhao, Baoping and Li, Eileena and Wall, Robert and Yang, Jinzeng},
title = {Coordinated patterns of gene expressions for adult muscle build-up
in transgenic mice expressing myostatin propeptide},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {305},
number = {1},
abstract = {BACKGROUND:Skeletal muscle growth and maintenance are essential for
human health. One of the muscle regulatory genes, namely myostatin,
a member of transforming growth factor-ß, plays a dominant role in
the genetic control of muscle mass. Myostatin is synthesized as a
precursor protein, which generates the N-terminal propeptide and
the C-terminal mature myostatin peptide by a post-translational cleavage
event. Previously, transgenic over-expression of myostatin propeptide
in skeletal muscle results in significant muscle growth in early
stages of development. The objectives of present study were to further
characterize muscle growth in later stages of life and to identify
genes and their expression patterns that are responsible for adult
muscle build-up by myostatin propeptide.RESULTS:Immunohistochemical
staining with an antibody to the N-terminus indicates a high level
of myostatin propeptide present in the muscles of transgenic mice
while there were no apparent differences in myostatin protein distribution
in the muscle fibers between the transgenic and wild-type mice. Main
individual muscles increased by 76–152% in the transgenic mice over
their wild-type littermate mice at 12 months of age. A large number
of nuclei were localized in the central and basal lamina of the myofibers
in the transgenic mice as the number of nuclei per fiber and 100
µm2 area was significantly higher in transgenic mice than wild-type
mice. By systemic comparisons of global mRNA expression patterns
between transgenic mice and wild-type littermates using microarray
and qRT-PCR techniques, we have identified distinct gene expression
patterns to support adult muscle build-up by myostatin propeptide,
which are comprised of enhanced expressions of myogenic regulatory
factors and extracelullar matrix components, and differentially down-regulated
expressions of genes related to protein degradation and mitochondrial
ATP synthesis.CONCLUSION:The results present a coordinated pattern
of gene expressions for reduced energy utilization during muscle
build-up in adult stage. Enhanced muscle buildup by myostatin propeptide
is sustained by reduced ATP synthesis as a result of a decreased
activity of protein degradation. Myostatin propeptide may have a
therapeutic application to the treatment of clinical muscle wasting
problems by depressing myostatin activity.},
doi = {10.1186/1471-2164-10-305},
issn = {1471-2164},
pubmedid = {19586544},
url = {http://www.biomedcentral.com/1471-2164/10/305}
}
@ARTICLE{Zhao2009a,
author = {Zhao, Chen and Ivanov, Ivan and Dougherty, Edward R. and Hartman,
Terryl J. and Lanza, Elaine and Bobe, Gerd and Colburn, Nancy H.
and Lupton, Joanne R. and Davidson, Laurie A. and Chapkin, Robert
S.},
title = {Noninvasive Detection of Candidate Molecular Biomarkers in Subjects
with a History of Insulin Resistance and Colorectal Adenomas},
journal = {Cancer Prevention Research},
year = {2009},
volume = {2},
pages = {590--597},
number = {6},
month = jun,
abstract = {We have developed novel molecular methods using a stool sample, which
contains intact sloughed colon cells, to quantify colonic gene expression
profiles. In this study, our goal was to identify diagnostic gene
sets (combinations) for the noninvasive classification of different
phenotypes. For this purpose, the effects of a legume-enriched, low
glycemic index, high fermentable fiber diet was evaluated in subjects
with four possible combinations of risk factors, including insulin
resistance and a history of adenomatous polyps. In a randomized crossover
design controlled feeding study, each participant (a total of 23;
5-12 per group) consumed the experimental diet (1.5 cups of cooked
dry beans) and a control diet (isocaloric average American diet)
for 4 weeks with a 3-week washout period between diets. Using prior
biological knowledge, the complexity of feature selection was reduced
to perform an exhaustive search on all allowable feature (gene) sets
of size 3, and among these, 27 had (unbiased) error estimates of
0.15 or less. Linear discriminant analysis was successfully used
to identify the best single genes and two- to three-gene combinations
for distinguishing subjects with insulin resistance, a history of
polyps, or exposure to a chemoprotective legume-rich diet. These
results support our premise that gene products (RNA) isolated from
stool have diagnostic value in terms of assessing colon cancer risk.},
url = {http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/2/6/590}
}
@ARTICLE{Zhao2009b,
author = {Zhao, Cheng-Ri and Ikka, Takashi and Sawaki, Yoshiharu and Kobayashi,
Yuriko and Suzuki, Yuji and Hibino, Takashi and Sato, Shigeru and
Sakurai, Nozomu and Shibata, Daisuke and Koyama, Hiroyuki},
title = {Comparative transcriptomic characterization of aluminum, sodium chloride,
cadmium and copper rhizotoxicities in Arabidopsis thaliana},
journal = {BMC Plant Biology},
year = {2009},
volume = {9},
pages = {32},
number = {1},
abstract = {BACKGROUND:Rhizotoxic ions in problem soils inhibit nutrient and water
acquisition by roots, which in turn leads to reduced crop yields.
Previous studies on the effects of rhizotoxic ions on root growth
and physiological functions suggested that some mechanisms were common
to all rhizotoxins, while others were more specific. To understand
this complex system, we performed comparative transcriptomic analysis
with various rhizotoxic ions, followed by bioinformatics analysis,
in the model plant Arabidopsis thaliana.RESULTS:Roots of Arabidopsis
were treated with the major rhizotoxic stressors, aluminum (Al) ions,
cadmium (Cd) ions, copper (Cu) ions and sodium (NaCl) chloride, and
the gene expression responses were analyzed by DNA array technology.
The top 2.5% of genes whose expression was most increased by each
stressor were compared with identify common and specific gene expression
responses induced by these stressors. A number of genes encoding
glutathione-S-transferases, peroxidases, Ca-binding proteins and
a trehalose-synthesizing enzyme were induced by all stressors. In
contrast, gene ontological categorization identified sets of genes
uniquely induced by each stressor, with distinct patterns of biological
processes and molecular function. These contained known resistance
genes for each stressor, such as AtALMT1 (encoding Al-activated malate
transporter) in the Al-specific group and DREB (encoding dehydration
responsive element binding protein) in the NaCl-specific group. These
gene groups are likely to reflect the common and differential cellular
responses and the induction of defense systems in response to each
ion. We also identified co-expressed gene groups specific to rhizotoxic
ions, which might aid further detailed investigation of the response
mechanisms.CONCLUSION:In order to understand the complex responses
of roots to rhizotoxic ions, we performed comparative transcriptomic
analysis followed by bioinformatics characterization. Our analyses
revealed that both general and specific genes were induced in Arabidopsis
roots exposed to various rhizotoxic ions. Several defense systems,
such as the production of reactive oxygen species and disturbance
of Ca homeostasis, were triggered by all stressors, while specific
defense genes were also induced by individual stressors. Similar
studies in different plant species could help to clarify the resistance
mechanisms at the molecular level to provide information that can
be utilized for marker-assisted selection.},
doi = {10.1186/1471-2229-9-32},
issn = {1471-2229},
pubmedid = {19309492},
url = {http://www.biomedcentral.com/1471-2229/9/32}
}
@ARTICLE{Zhao2009c,
author = {Zhao, Hongxing and Boije, Henrik and Granberg, Fredrik and Pettersson,
Ulf and Svensson, Catharina},
title = {Activation of the interferon-induced STAT pathway during an adenovirus
type 12 infection},
journal = {Virology},
year = {2009},
volume = {392},
pages = {186--195},
number = {2},
month = sep,
abstract = {We have previously described a temporal regulation of host cell gene
expression during adenovirus type 2 infection (Ad2) of primary human
fibroblasts. Among the eleven percent of genes deregulated by Ad2,
a large fraction included genes involved in cell cycle, growth control
and antiviral defense, consistent with the capacity of Ad2 to efficiently
master the infected cell and cause an effectively productive infection.
Adenovirus type 12 (Ad12), which belongs to the highly oncogenic
subgroup, is characterised by slow progression, less cytopathic effect
and lower virus yield compared to the non-oncogenic Ad2. Microarray
analysis of host cell gene expression in Ad12 infected human lung
fibroblasts (IMR90) demonstrated a quantitatively and qualitatively
less impact on host cell gene expression, compared to Ad2. Of the
relatively few genes up regulated during the course of Ad12 infection
only two (5%) were identified as potential E2F targets, compared
to the significant activation of E2F-dependent transcription observed
during an Ad2 infection. Although approximately 30% of the genes
deregulated by Ad12 were previously identified in Ad2-infected cells,
a distinct difference was observed in a group of interferon-stimulated
genes (ISGs). G1P2, IFI6, IFI16, IFIT1, IFIT2, IFITM1 and IRF9 were
activated during the very late stage of infection, and a consistent
induction of IFN[beta] gene expression, preceding induction of the
ISGs, was demonstrated by quantitative real-time PCR analysis. An
activated JAK/STAT signalling pathway was also indicated by the accumulation
of all components (STAT1, STAT2 and IRF9) of the ISGF3 transcription
factor. Significantly, none of these ISGs was activated in Ad2 infected
IMR90 cells. Thus, the inability of Ad12 to evade the interferon
response might explain its restricted virulence.},
issn = {0042-6822},
keywords = {Adenovirus type 12, cDNA microarray, IMR90 cells, Interferon-stimulated
genes (ISG)},
url = {http://www.sciencedirect.com/science/article/B6WXR-4WYCT1G-2/2/b06bad3695ade90afb6fc59aa4f4789f}
}
@ARTICLE{Zhao2012,
author = {Hongxing Zhao and Martin Dahlö and Anders Isaksson and Ann-Christine
Syvänen and Ulf Pettersson},
title = {The transcriptome of the adenovirus infected cell},
journal = {Virology},
year = {2012},
pages = { - },
number = {0},
abstract = {Alternations of cellular gene expression following an adenovirus type
2 infection of human primary cells were studied by using superior
sensitive cDNA sequencing. In total, 3791 cellular genes were identified
as differentially expressed more than 2-fold. Genes involved in DNA
replication, RNA transcription and cell cycle regulation were very
abundant among the up-regulated genes. On the other hand, genes involved
in various signaling pathways including TGF-β, Rho, G-protein, Map
kinase, STAT and NF-κB stood out among the down-regulated genes.
Binding sites for E2F, ATF/CREB and AP2 were prevalent in the up-regulated
genes, whereas binding sites for SRF and NF-κB were dominant among
the down-regulated genes. It is evident that the adenovirus has gained
a control of the host cell cycle, growth, immune response and apoptosis
at 24 h after infection. However, efforts from host cell to
block the cell cycle progression and activate an antiviral response
were also observed.},
doi = {10.1016/j.virol.2011.12.006},
issn = {0042-6822},
keywords = {Adenovirus type 2},
url = {http://www.sciencedirect.com/science/article/pii/S0042682211005642}
}
@ARTICLE{Zhao2007,
author = {Zhao, Hui and Friedman, Richard D. and Fournier, R. E. K.},
title = {The Locus Control Region Activates Serpin Gene Expression through
Recruitment of Liver-Specific Transcription Factors and RNA Polymerase
II},
journal = {Mol. Cell. Biol.},
year = {2007},
volume = {27},
pages = {5286--5295},
number = {15},
month = aug,
abstract = {The human serine protease inhibitor (serpin) gene cluster at 14q32.1
comprises 11 serpin genes, many of which are expressed specifically
in hepatic cells. Previous studies identified a locus control region
(LCR) upstream of the human {alpha}1-antitrypsin ({alpha}1AT) gene
that is required for gene activation, chromatin remodeling, and histone
acetylation throughout the proximal serpin subcluster. Here we show
that the LCR interacts with multiple liver-specific transcription
factors, including hepatocyte nuclear factor 3{beta} (HNF-3{beta}),
HNF-6{alpha}, CCAAT/enhancer binding protein alpha (C/EBP{alpha}),
and C/EBP{beta}. RNA polymerase II is also recruited to the locus
through the LCR. Nongenic transcription at both the LCR and an upstream
regulatory region was detected, but the deletion of the LCR abolished
transcription at both sites. The deletion of HNF-3 and HNF-6 binding
sites within the LCR reduced histone acetylation at both the LCR
and the upstream regulatory region and decreased the transcription
of the {alpha}1AT, corticosteroid binding globulin, and protein Z-dependent
protease inhibitor genes. These results suggest that the LCR activates
genes in the proximal serpin subcluster by recruiting liver-specific
transcription factors and components of the general transcription
machinery to regulatory regions upstream of the {alpha}1AT gene.},
url = {http://mcb.asm.org/cgi/content/abstract/27/15/5286}
}
@ARTICLE{Zhao2003,
author = {Zhao, Hongxing and Granberg, Fredrik and Elfineh, Ludmila and Pettersson,
Ulf and Svensson, Catharina},
title = {Strategic Attack on Host Cell Gene Expression during Adenovirus Infection},
journal = {J. Virol.},
year = {2003},
volume = {77},
pages = {11006--11015},
number = {20},
month = oct,
abstract = {To understand the interaction between the virus and its host, we used
three sources of cDNA microarrays to examine the expression of 12,309
unique genes at 6 h postinfection of HeLa cells with high multiplicities
of adenovirus type 2. Seventy-six genes with significantly changed
expression ratios were identified, suggesting that adenovirus only
modulates expression of a limited set of cellular genes. Quantitative
real-time PCR analyses on selected genes were performed to confirm
the microarray results. Significantly, a pronounced transcriptional
activation by the promiscuous E1A-289R transcriptional activator
was not apparent. Instead, promoter sequences in 45% of the upregulated
genes harbored a potential E2F binding site, suggesting that the
ability of the amino-terminal domain of E1A to regulate E2F-dependent
transcription may be a major pathway for regulation of cellular gene
expression. CDC25A was the only upregulated gene directly involved
in cell cycle control. In contrast, several genes implicated in cell
growth arrest were repressed. The transforming growth factor beta
superfamily was specifically affected in the expression of both the
upstream ligand and an intracellular regulator. In agreement with
previous reports, adenovirus also targeted the innate immune response
by downregulating several cytokines, including CLL2, CXCL1, and interleukin-6.
Finally, stress response genes encoding GADD45B, ATF3, and TP53AP1
were upregulated. Importantly, we also found a novel countermeasure--activation
of the apoptosis inhibitor survivin.},
url = {http://jvi.asm.org/cgi/content/abstract/77/20/11006}
}
@ARTICLE{Zhao2007a,
author = {Zhao, Hongxing and Granberg, Fredrik and Pettersson, Ulf},
title = {How adenovirus strives to control cellular gene expression},
journal = {Virology},
year = {2007},
volume = {363},
pages = {357--375},
number = {2},
month = jul,
abstract = {Host cell gene expression during the course of a human adenovirus
infection in synchronized primary human lung fibroblasts was analyzed
using cDNA microarrays. The slow progression of the infectious cycle
in these cells allowed a detailed examination of cellular gene regulation.
In total, 988 unique genes were identified as differentially expressed
more than 2-fold. The cellular gene expression profiles closely correlated
to the progression of the infection. Based on the observed expression
patterns, the deregulation of cellular genes' expression could be
separated into four periods: (i) the immediate response of the host
to incoming virus; (ii) deregulation of cellular genes involved in
cell cycle, growth control, and antiviral response; (iii) steady-state
regulation of cellular gene expression during viral DNA replication;
(iv) targeting of cellular genes involved in intra- and extra-cellular
structure at the late phase of infection. The struggle of the virus
to gain control of TGF-[beta] and Wnt signaling, as well as the apoptotic
pathways, was conspicuous.},
issn = {0042-6822},
keywords = {Adenovirus, Microarray, Time course, Host cell gene expression},
url = {http://www.sciencedirect.com/science/article/B6WXR-4NC5SW6-1/2/4e574381b2eca5305883d128a00531d7}
}
@ARTICLE{Zhao2005a,
author = {Zhao, Hongjuan and Kim, Young and Wang, Pei and Lapointe, Jacques
and Tibshirani, Rob and Pollack, Jonathan R. and Brooks, James D.},
title = {Genome-wide characterization of gene expression variations and DNA
copy number changes in prostate cancer cell lines},
journal = {Prostate},
year = {2005},
volume = {63},
pages = {187--197},
number = {2},
abstract = {Abstract 10.1002/pros.20158.abs BACKGROUND The aim of this study was
to characterize gene expression and DNA copy number profiles in androgen
sensitive (AS) and androgen insensitive (AI) prostate cancer cell
lines on a genome-wide scale. METHODS Gene expression profiles and
DNA copy number changes were examined using DNA microarrays in eight
commonly used prostate cancer cell lines. Chromosomal regions with
DNA copy number changes were identified using cluster along chromosome
(CLAC). RESULTS There were discrete differences in gene expression
patterns between AS and AI cells that were not limited to androgen-responsive
genes. AI cells displayed more DNA copy number changes, especially
amplifications, than AS cells. The gene expression profiles of cell
lines showed limited similarities to prostate tumors harvested at
surgery. CONCLUSIONS AS and AI cell lines are different in their
transcriptional programs and degree of DNA copy number alterations.
This dataset provides a context for the use of prostate cancer cell
lines as models for clinical cancers. © 2004 Wiley-Liss, Inc.},
issn = {1097-0045},
keywords = {androgen, microarray, aCGH, tumor subtypes, metastasis, prostate cancer
cell lines},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/pros.20158}
}
@ARTICLE{Zhao2004,
author = {Zhao, Hongjuan and Langerod, Anita and Ji, Youngran and Nowels, Kent
W. and Nesland, Jahn M. and Tibshirani, Rob and Bukholm, Ida K. and
Karesen, Rolf and Botstein, David and Borresen-Dale, Anne-Lise and
Jeffrey, Stefanie S.},
title = {Different Gene Expression Patterns in Invasive Lobular and Ductal
Carcinomas of the Breast},
journal = {Mol. Biol. Cell},
year = {2004},
volume = {15},
pages = {2523--2536},
number = {6},
month = jun,
abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC)
are the two major histological types of breast cancer worldwide.
Whereas IDC incidence has remained stable, ILC is the most rapidly
increasing breast cancer phenotype in the United States and Western
Europe. It is not clear whether IDC and ILC represent molecularly
distinct entities and what genes might be involved in the development
of these two phenotypes. We conducted comprehensive gene expression
profiling studies to address these questions. Total RNA from 21 ILCs,
38 IDCs, two lymph node metastases, and three normal tissues were
amplified and hybridized to [~]42,000 clone cDNA microarrays. Data
were analyzed using hierarchical clustering algorithms and statistical
analyses that identify differentially expressed genes (significance
analysis of microarrays) and minimal subsets of genes (prediction
analysis for microarrays) that succinctly distinguish ILCs and IDCs.
Eleven of 21 (52%) of the ILCs ("typical" ILCs) clustered together
and displayed different gene expression profiles from IDCs, whereas
the other ILCs ("ductal-like" ILCs) were distributed between different
IDC subtypes. Many of the differentially expressed genes between
ILCs and IDCs code for proteins involved in cell adhesion/motility,
lipid/fatty acid transport and metabolism, immune/defense response,
and electron transport. Many genes that distinguish typical and ductal-like
ILCs are involved in regulation of cell growth and immune response.
Our data strongly suggest that over half the ILCs differ from IDCs
not only in histological and clinical features but also in global
transcription programs. The remaining ILCs closely resemble IDCs
in their transcription patterns. Further studies are needed to explore
the differences between ILC molecular subtypes and to determine whether
they require different therapeutic strategies.},
url = {http://www.molbiolcell.org/cgi/content/abstract/15/6/2523}
}
@ARTICLE{Zhao2004a,
author = {Zhao, Hongjuan and Whitfield, Michael L. and Xu, Tong and Botstein,
David and Brooks, James D.},
title = {Diverse Effects of Methylseleninic Acid on the Transcriptional Program
of Human Prostate Cancer Cells},
journal = {Mol. Biol. Cell},
year = {2004},
volume = {15},
pages = {506--519},
number = {2},
month = feb,
abstract = {Methylseleninic acid (MSA) has been shown to have potent anticancer
activity and is an excellent compound for studying the anticancer
effects of selenium in vitro. To gain insights into the effects of
MSA in prostate cancer, we characterized the global transcriptional
response of LNCaP, an androgen-sensitive human prostate cancer cell
line, to MSA by using high-density cDNA microarrays. We identified
951 genes whose expression shows striking dose- and time-dependent
changes in response to 3-30 {micro}M MSA over the time course of
48 h. Transcript levels of many cell cycle-regulated genes change
in response to MSA, suggesting that MSA inhibits proliferation. Consistent
with these gene expression changes, cell proliferation, monitored
by carboxyfluoroscein succinimidyl ester staining, was decreased
after MSA treatment, and an accumulation of cells at G0/G1 phase
was detected by flow cytometry. Surprisingly, MSA also modulated
expression of many androgen-regulated genes, suppressed androgen
receptor (AR) expression at both mRNA and protein level, and decreased
levels of prostate specific antigen secreted into the medium. Low
concentrations of MSA also induced significant increases in transcript
levels of phase 2 detoxification enzymes and induced NADPH dehydrogenase,
quinone 1 enzymatic activity, a surrogate marker of global phase
2 enzyme activity. Our results suggest that MSA may protect against
prostate cancer by inhibiting cell proliferation, by modulating the
expression of AR and AR-regulated genes and by inducing carcinogen
defenses.},
url = {http://www.molbiolcell.org/cgi/content/abstract/15/2/506}
}
@ARTICLE{Zhao2008a,
author = {Zhao, Hong-Ye and Ooyama, Akio and Yamamoto, Masatatsu and Ikeda,
Ryuji and Haraguchi, Misako and Tabata, Sho and Furukawa, Tatsuhiko
and Che, Xiao-Fang and Iwashita, Ken-ichi and Oka, Toshinori and
Fukushima, Masakazu and Nakagawa, Masayuki and Ono, Mayumi and Kuwano,
Michihiko and Akiyama, Shin-ichi},
title = {Down regulation of c-Myc and induction of an angiogenesis inhibitor,
thrombospondin-1, by 5-FU in human colon cancer KM12C cells},
journal = {Cancer Letters},
year = {2008},
volume = {270},
pages = {156--163},
number = {1},
month = oct,
issn = {0304-3835},
keywords = {5-Fluorouracil, Genechip analysis, Thrombospondin-1, c-Myc},
url = {http://www.sciencedirect.com/science/article/B6T54-4SV6PKV-1/2/32436a86f27f4668132df4bfc552856d}
}
@ARTICLE{Zhao2007b,
author = {Zhao, Jia and Chang, Andrew C. and Li, Chen and Shedden, Kerby A.
and Thomas, Dafydd G. and Misek, David E. and Manoharan, Arun Prasad
and Giordano, Thomas J. and Beer, David G. and Lubman, David M.},
title = {Comparative Proteomics Analysis of Barrett Metaplasia and Esophageal
Adenocarcinoma Using Two-dimensional Liquid Mass Mapping},
journal = {Mol. Cell. Proteomics},
year = {2007},
volume = {6},
pages = {987--999},
number = {6},
month = jun,
abstract = {Esophageal adenocarcinoma, currently the seventh leading cause of
cancer-related death, has been associated with the presence of Barrett
metaplasia. The malignant potential of Barrett metaplasia is evidenced
by ultimate progression of this condition to invasive adenocarcinoma.
We utilized liquid phase separation of proteins with chromatofocusing
in the first dimension and nonporous reverse phase HPLC in the second
dimension followed by ESI-TOF mass spectrometry to identify proteins
differentially expressed in six Barrett metaplasia samples as compared
with six esophageal adenocarcinoma samples; all six Barrett samples
were obtained from the identical six patients from whom we obtained
the esophageal adenocarcinoma tissue. Approximately 300 protein bands
were detected by mass mappings, and 38 differentially expressed proteins
were identified by {micro}LC-MS/MS. The false positive rates of the
peptide identifications were evaluated by reversed database searching.
Among the proteins that were identified, Rho GDP dissociation inhibitor
2, {alpha}-enolase, Lamin A/C, and nucleoside-diphosphate kinase
A were demonstrated to be up-regulated in both mRNA and protein expression
in esophageal adenocarcinomas relative to Barrett metaplasia. Candidate
proteins were examined at the mRNA level using high density oligonucleotide
microarrays. The cellular expression patterns were verified in both
esophageal adenocarcinomas and in Barrett metaplasia by immunohistochemistry.
These differentially expressed proteins may have utility as useful
candidate markers of esophageal adenocarcinoma.},
url = {http://www.mcponline.org/cgi/content/abstract/6/6/987}
}
@ARTICLE{Zhao2011a,
author = {Zhao, Liang and Glazov, Evgeny A. and Pattabiraman, Diwakar R. and
Al-Owaidi, Faisal and Zhang, Ping and Brown, Matthew A. and Leo,
Paul J. and Gonda, Thomas J.},
title = {Integrated genome-wide chromatin occupancy and expression analyses
identify key myeloid pro-differentiation transcription factors repressed
by Myb},
journal = {Nucleic Acids Res.},
year = {2011},
volume = {39},
pages = {4664-4679},
number = {11},
abstract = {To gain insight into the mechanisms by which the Myb transcription
factor controls normal hematopoiesis and particularly, how it contributes
to leukemogenesis, we mapped the genome-wide occupancy of Myb by
chromatin immunoprecipitation followed by massively parallel sequencing
(ChIP-Seq) in ERMYB myeloid progenitor cells. By integrating the
genome occupancy data with whole genome expression profiling data,
we identified a Myb-regulated transcriptional program. Gene signatures
for leukemia stem cells, normal hematopoietic stem/progenitor cells
and myeloid development were overrepresented in 2368 Myb regulated
genes. Of these, Myb bound directly near or within 793 genes. Myb
directly activates some genes known critical in maintaining hematopoietic
stem cells, such as Gfi1 and Cited2. Importantly, we also show that,
despite being usually considered as a transactivator, Myb also functions
to repress approximately half of its direct targets, including several
key regulators of myeloid differentiation, such as Sfpi1 (also known
as Pu.1), Runx1, Junb and Cebpb. Furthermore, our results demonstrate
that interaction with p300, an established coactivator for Myb, is
unexpectedly required for Myb-mediated transcriptional repression.
We propose that the repression of the above mentioned key pro-differentiation
factors may contribute essentially to Myb's ability to suppress differentiation
and promote self-renewal, thus maintaining progenitor cells in an
undifferentiated state and promoting leukemic transformation.},
doi = {10.1093/nar/gkr024},
eprint = {http://nar.oxfordjournals.org/cgi/reprint/39/11/4664.pdf},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/39/11/4664}
}
@ARTICLE{Zhao2009d,
author = {Zhao, Nan and Boyle, Brian and Duval, Isabelle and Ferrer, Jean-Luc
and Lin, Hong and Seguin, Armand and Mackay, John and Chen, Feng},
title = {SABATH methyltransferases from white spruce (Picea glauca): gene
cloning, functional characterization and structural analysis},
journal = {Tree Physiol},
year = {2009},
volume = {29},
pages = {947--957},
number = {7},
month = jul,
abstract = {Known members of the plant SABATH family of methyltransferases have
important biological functions by methylating hormones, signalling
molecules and other metabolites. While all previously characterized
SABATH genes were isolated from angiosperms, in this article, we
report on the isolation and functional characterization of SABATH
genes from white spruce (Picea glauca [Moench] Voss), a gymnosperm.
Through EST database search, three genes that encode proteins significantly
homologous to known SABATH proteins were identified from white spruce.
They were named PgSABATH1, PgSABATH2 and PgSABATH3, respectively.
Full length cDNAs of these three genes were cloned and expressed
in Escherichia coli. The E. coli-expressed recombinant proteins were
tested for methyltransferase activity with a large number of compounds.
While no activity was detected for PgSABATH2 and PgSABATH3, PgSABATH1
displayed the highest level of catalytic activity with indole-3-acetic
acid (IAA). PgSABATH1 was, therefore, renamed PgIAMT1. Under steady-state
conditions, PgIAMT1 exhibited apparent Km values of 18.2 {micro}M
for IAA. Homology-based structural modelling of PgIAMT1 revealed
that the active site of PgIAMT1 is highly similar to other characterized
IAMTs from angiosperms. PgIAMT1 showed expression in multiple tissues,
with the highest level of expression detected in embryonic tissues.
During somatic embryo maturation, a significant reduction in PgIAMT1
transcript levels was observed when developing cotyledons become
apparent which is indicative of mature embryos. The biological roles
of white spruce SABATH genes, especially those of PgIAMT1, and the
evolution of the SABATH family are discussed.},
url = {http://treephys.oxfordjournals.org/cgi/content/abstract/29/7/947}
}
@ARTICLE{Zhao2011b,
author = {Pingsen Zhao and Lili Zhao and Tao Zhang and Yinglin Qi and Tiecheng
Wang and Kejian Liu and Hualei Wang and Hao Feng and Hongli Jin and
Chuan Qin and Songtao Yang and Xianzhu Xia},
title = {Innate immune response gene expression profiles in central nervous
system of mice infected with rabies virus},
journal = {Comparative Immunology, Microbiology and Infectious Diseases},
year = {2011},
volume = {34},
pages = {503 - 512},
number = {6},
abstract = {The present study was focused on the modulation of innate immune response
genes in CNS of mouse in response to rabies virus (RABV) infection.
The global gene expression changes in brains of RABV- or mock-infected
mice were investigated using DNA microarray analysis and quantitative
real-time PCR. Then functional enrichment of the differentially expressed
mRNAs was performed. Microarray analysis showed that 390 genes in
brain were significantly (P < 0.01) regulated in response
to RABV infection, with obviously up-regulated genes like interferon
(IFN) stimulated genes (ISGs), IFN inducible transcription factors,
cytokines and complement, etc. The significant pathways of differentially
expressed genes are mainly involved in JAK-STAT signaling pathway,
antigen processing and presentation, ubiquitin mediated proteolysis
and complement cascades. The results suggest that the modulated genes
in infected CNS were possibly involved in pathogenesis of rabies.
Conversely, they may have protective effects.},
doi = {10.1016/j.cimid.2011.09.003},
issn = {0147-9571},
keywords = {Rabies virus},
url = {http://www.sciencedirect.com/science/article/pii/S0147957111000774}
}
@ARTICLE{Zhao2012a,
author = {Pingsen Zhao and Lili Zhao and Tao Zhang and Hualei Wang and Chuan
Qin and Songtao Yang and Xianzhu Xia},
title = {Changes in microRNA expression induced by rabies virus infection
in mouse brains},
journal = {Microbial Pathogenesis},
year = {2012},
volume = {52},
pages = {47 - 54},
number = {1},
abstract = {MicroRNAs (miRNAs) are small RNA (≈22 nt) molecules expressed endogenously
in cells. They are involved in the regulation of gene expression.
Recently, evidence has shown that cellular miRNAs have key regulatory
roles in virus–host interactions. The rabies virus (RABV) causes
a fatal infection of the central nervous systems (CNS) of warm-blooded
animals, yet its pathogenesis remains poorly understood. To gain
more insight into the pathogenesis of RABV, a miRNA microarray was
performed as part of an investigation of changes in host miRNA expression
in the brains of mice infected with RABV. The results showed that
RABV infection induced modulation of the expression of sixteen miRNA
molecules. These data were verified by real-time PCR. Functional
analysis showed the differentially expressed miRNAs to be involved
in many immune-related signaling pathways, such as the RIG-I-like
receptor signaling pathway, JAK-STAT signaling pathway, chemokine
signaling pathway, T-cell receptor signaling pathway, MAPK signaling
pathway, leukocyte transendothelial migration, and natural killer
cell mediated cytotoxicity. The predicted expression levels of the
target genes of these modulated miRNAs correlated with measurements
of gene expression measured by DNA microarray and qRT-PCR.},
doi = {10.1016/j.micpath.2011.10.001},
issn = {0882-4010},
keywords = {Rabies virus},
url = {http://www.sciencedirect.com/science/article/pii/S0882401011001720}
}
@ARTICLE{Zhao2010a,
author = {Zhao, Qi and Kirkness, Ewen and Caballero, Otavia and Galante, Pedro
and Parmigiani, Raphael and Edsall, Lee and Kuan, Samantha and Ye,
Zhen and Levy, Samuel and Vasconcelos, Ana Tereza and Ren, Bing and
de Souza, Sandro and Camargo, Anamaria and Simpson, Andrew and Strausberg,
Robert},
title = {Systematic detection of putative tumor suppressor genes through the
combined use of exome and transcriptome sequencing},
journal = {Genome Biology},
year = {2010},
volume = {11},
pages = {R114},
number = {11},
abstract = {BACKGROUND:To identify potential tumor suppressor genes, genome-wide
data from exome and transcriptome sequencing were combined to search
for genes with loss of heterozygosity and allele-specific expression.
The analysis was conducted on the breast cancer cell line HCC1954,
and a lymphoblast cell line from the same individual, HCC1954BL.RESULTS:By
comparing exome sequences from the two cell lines, we identified
loss of heterozygosity events at 403 genes in HCC1954 and at one
gene in HCC1954BL. The combination of exome and transcriptome sequence
data also revealed 86 and 50 genes with allele specific expression
events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of
genes surveyed, respectively. Many of these genes identified by loss
of heterozygosity and allele-specific expression are known or putative
tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate
in DNA repair pathways.CONCLUSIONS:Our results demonstrate that the
combined application of high throughput sequencing to exome and allele-specific
transcriptome analysis can reveal genes with known tumor suppressor
characteristics, and a shortlist of novel candidates for the study
of tumor suppressor activities.},
doi = {10.1186/gb-2010-11-11-r114},
issn = {1465-6906},
pubmedid = {21108794},
url = {http://genomebiology.com/2010/11/11/R114}
}
@ARTICLE{Zhao2005b,
author = {Zhao, Shu-Hong and Recknor, Justin and Lunney, Joan K. and Nettleton,
Dan and Kuhar, Daniel and Orley, Sarah and Tuggle, Christopher K.},
title = {Validation of a first-generation long-oligonucleotide microarray
for transcriptional profiling in the pig},
journal = {Genomics},
year = {2005},
volume = {86},
pages = {618--625},
number = {5},
month = nov,
abstract = {A first-generation porcine oligonucleotide set, representing 13,297
cDNAs and ESTs, has been designed by Qiagen-Operon for transcriptional
profiling. To validate this set, microarrays containing each 70-mer
oligonucleotide, referred to as the Qiagen-NRSP8 array, were hybridized
with targets from porcine adult liver, lung, muscle, or small intestine.
Transcriptome analyses showed that 11,328 of the oligonucleotides
demonstrated expression in at least one tissue. Statistical analyses
revealed that 1810 genes showed differential expression among tissues
(Bonferroni adjusted p < 0.05). Biological pathways identified by
DAVID/EASE analysis using a list of 423 tissue-selective genes matched
archetypal pathways in the corresponding human or mouse tissue. Real-time
quantitative PCR confirmed expression patterns for 9 of 11 genes
tested. Our results demonstrate that this first-generation porcine
oligonucleotide array is informative and the specificity is high.
This is essential validation for investigators using the Qiagen-NRSP8
array for porcine functional genomics and for using the pig in modeling
important physiological problems.},
issn = {0888-7543},
keywords = {Pig, Long oligonucleotide microarray, Transcriptional profiling, Tissue},
url = {http://www.sciencedirect.com/science/article/B6WG1-4H8VJCJ-2/2/cb2e70542c0170f71c878eaa7160ab20}
}
@ARTICLE{Zhao2011c,
author = {Zhao, Tieqiang and Zhao, Wenyuan and Chen, Yuanjian and Ahokas, Robert
A. and Sun, Yao},
title = {Acidic and basic fibroblast growth factors involved in cardiac angiogenesis
following infarction},
journal = {International Journal of Cardiology},
year = {2011},
volume = {152,3},
pages = {307-313},
abstract = {Acidic and basic fibroblast growth factors (FGF-1/FGF-2) promote angiogenesis
in cancer. Angiogenesis is integral to cardiac repair following myocardial
infarction (MI). The potential regulation of FGF-1/FGF-2 in cardiac
angiogenesis postMI remains unexplored. Herein, we examined the temporal
and spatial expression of FGF-1/FGF-2 and FGF receptors (FGFR) in
the infarcted rat heart at days 1, 3, 7, and 14 postMI. FGF-1/-2
gene and protein expression, cells expressing FGF-1/-2 and FGFR expression
were examined by quantitative in situ hybridization, RT-PCR; western
blot, immunohistochemistry and quantitative in vitro autoradiography.
Compared to the normal heart, we found that in the border zone and
infarcted myocardium 1) FGF-1 gene expression was increased in the
first week postMI and returned to control levels at week 2; FGF-1
protein levels were, however, largely reduced at day 1, then elevated
at day 3 peaked at day 7 and declined at day 14; and cells expressing
FGF-1 were primarily inflammatory cells; 2) FGF-2 gene expression
was significantly elevated from day 1 to day 14; the increase in
FGF-2 protein level was most evident at day 7 and cells expressing
FGF-2 were primarily endothelial cells; 3) FGFR expression started
to increase at day 3 and remained elevated thereafter; and 4) FGF-1/FGF-2
and FGFR expression remained unchanged in the noninfarcted myocardium.
Thus, FGF-1/FGF-2 and FGFR expression are enhanced in the infarcted
myocardium in the early stage after MI, which is spatially and temporally
coincident with angiogenesis, suggesting that FGF-1/FGF-2 are involved
in regulating cardiac angiogenesis and repair.},
issn = {0167-5273},
keywords = {Myocardial infarction, Angiogenesis, FGF-1, FGF-2, FGFR},
url = {http://www.sciencedirect.com/science/article/pii/S0167527310005516}
}
@ARTICLE{Zhao2004b,
author = {Zhao, Wenyuan and Lu, Li and Chen, Sue S. and Sun, Yao},
title = {Temporal and spatial characteristics of apoptosis in the infarcted
rat heart},
journal = {Biochemical and Biophysical Research Communications},
year = {2004},
volume = {325},
pages = {605--611},
number = {2},
month = dec,
abstract = {Following myocardial infarction (MI), tissue repair/remodeling occurs
in both the infarcted and noninfarcted myocardium. Apoptosis has
been demonstrated to play an important role in these processes. In
the present study, we sought to determine the temporal and spatial
characteristics of apoptosis in the infarcted heart as well as to
identify cells undergoing programmed cell death at different stages
of repair/remodeling and their relationship to the expression of
anti-/pro-apoptotic genes following MI. Our study has shown that
apoptosis appears in both infarcted and noninfarcted myocardium,
and cells undergoing apoptosis depend on the stage of healing. In
the infarcted myocardium, apoptosis contributes to the loss of cardiomyocytes
during the early stage of healing, elimination of inflammatory cells
during the inflammatory phase of healing, and reduction of myofibroblasts
with the fibrogenic phase of repair in the infarcted myocardium.
In noninfarcted myocardium, cardiomyocyte apoptosis was observed
from day 3 to 28 postMI. Cardiac apoptosis following MI is correlated
with the increase of Bax expression.},
issn = {0006-291X},
keywords = {Myocardial infarction, Apoptosis, Bax, Bcl-2, Rats},
url = {http://www.sciencedirect.com/science/article/B6WBK-4DR1N67-F/2/08ae386b57f41fb65f451e75bc3f8022}
}
@ARTICLE{Zhao2008b,
author = {Zhao, Xiaoxian and Qiu, Wansong and Kung, Jiachun and Zhao, Xinyu
and Peng, Xuejun and Yegappan, Mani and Yen-Lieberman, Belinda and
Hsi, Eric D.},
title = {Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma
cell lines and is associated with reduced c-FLIP expression: A gene
expression profiling study with implications for potential combination
therapies},
journal = {Leukemia Research},
year = {2008},
volume = {32},
pages = {275--285},
number = {2},
month = feb,
abstract = {The Hodgkin cells and Reed-Sternberg cells (HRS) of classical Hodgkin
lymphoma (CHL) are derived from germinal center B cells. The pathogenesis
of CHL is unclear but constitutive activation of NF[kappa]B may contribute.
Proteasome inhibition aimed at inhibiting NF[kappa]B has been shown
to result in apoptosis in HRS cells. Here we investigated the effects
of bortezomib, a proteasome inhibitor, in HRS cells with a combination
of functional assays and gene expression profiling (GEP). Exposure
of KMH2 and L428 cells to bortezomib resulted in inhibition of proliferation
and induction of apoptosis. Gene expression analysis of KMH2 cells
by oligonucleotide cDNA microarrays showed that a limited set of
genes were differentially expressed involving several key cellular
pathways including cell cycle and apoptosis. Among them, the caspase
8 inhibitor cFLIP was down-regulated and confirmed by Q-PCR. Given
the evidence that cFLIP in HRS cells contribute to cells' insensitive
to death receptor-mediated apoptosis, we combined bortezomib and
TRAIL. This combination caused further down-regulation of cFLIP protein
and increased apoptosis in CHL cells demonstrated by PARP p85 immunohistochemistry
and immunoblotting. Such apoptotic effects were inhibited by caspase
inhibitor z-VAD-FMK, confirming the pro-apoptotic effects of bortezomib
and TRAIL are caspase-dependent. Bortezomib has no detectable effect
on expression of TRAIL receptor DR4/DR5 in these two cell lines.
Tissue microarray analysis of primary Hodgkin lymphomas displayed
that 82% cases (95/116) expressed cFLIP in Reed-Sternberg cells.
The discovery of apoptotic pathways that can be manipulated by proteasome
inhibition provides rationale for the combination of bortezomib and
agents such as TRAIL in CHL treatment.},
issn = {0145-2126},
keywords = {Bortezomib, TRAIL, cFLIP, Proteasome inhibitor, Apoptosis, Hodgkin
lymphoma, Cancer therapy},
url = {http://www.sciencedirect.com/science/article/B6T98-4P77G8W-1/2/a480b67482598648fae1540ee8d89bdf}
}
@ARTICLE{Zhao2010,
author = {Zhao, Yulian and Garcia, Jairo and Kolp, Lisa and Cheadle, Christopher
and Rodriguez, Annabelle and Vlahos, Nikos F.},
title = {The impact of luteal phase support on gene expression of extracellular
matrix protein and adhesion molecules in the human endometrium during
the window of implantation following controlled ovarian stimulation
with a GnRH antagonist protocol},
journal = {Fertil Steril},
year = {2010},
volume = {94},
pages = {2264--2271},
number = {6},
month = nov,
abstract = {To evaluate the impact of two different luteal phase support protocols
on gene expression of extracellular matrix (ECM) proteins and adhesion
molecules in the human endometrium. Eighty-four ECM protein and adhesion
molecule genes were analyzed using array-based reverse-transcription
polymerase chain reaction. Academic hospital. Nine oocyte donors.
Endometrial biopsies were obtained on the day of oocyte retrieval
(group I) and 3–5 days later (group II) after randomization into
3 groups. Group IIa had no luteal phase support, group IIb had luteal
support with micronized progesterone, and group IIc had luteal support
with progesterone plus 17β-estradiol. Gene expression profiles in
relation to different types of luteal phase support protocols. Compared
with the day of retrieval (group I), 24 genes were significantly
up-regulated (4 in group IIa, 14 in group IIb, 22 in group IIc) and
14 genes were down-regulated (5 in group IIa, 2 in group IIb, 10
in group IIc) on day 3–5 (P<.05). In the luteal support group,
up- regulation occurred predominantly in genes encoding for matrix
metallopeptidases (MMP10, MMP3, MMP9), integrins (ITGA3, ITGA5, ITGB3,
ITGB4), and laminin (LAMB3). In contrast, the most significant suppression
was documented in genes encoding for catenin-D2, collagen-11A1, and
the laminins (LAMA1 and LAMA3). Significant changes between groups
IIb and IIc were also observed in 9 genes. Luteal phase support following
controlled ovarian stimulation has a profound impact on the ECM pathway
targeted genes.},
issn = {0015-0282},
keywords = {Ovarian stimulation, luteal phase, microarray, extracellular matrix,
adhesion molecules, implantation},
publisher = {Elsevier for the American Society for Reproductive Medicine.},
refid = {S0015-0282(10)00143-3},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0015028210001433?showall=true}
}
@ARTICLE{Zhao2011,
author = {Zhao, Yanxin and Rempe, David A},
title = {Prophylactic neuroprotection against stroke: low-dose, prolonged
treatment with deferoxamine or deferasirox establishes prolonged
neuroprotection independent of HIF-1 function},
journal = {J Cereb Blood Flow Metab},
year = {2011},
pages = {--},
month = jan,
issn = {0271-678X},
publisher = {International Society for Cerebral Blood Flow \& Metabolism, Inc.},
url = {http://dx.doi.org/10.1038/jcbfm.2010.230}
}
@ARTICLE{Zhao2006a,
author = {Zhao, Yongmei and Rivieccio, Mark A. and Lutz, Sarah and Scemes,
Eliana and Brosnan, Celia F.},
title = {The TLR3 ligand polyI:C downregulates connexin 43 expression and
function in astrocytes by a mechanism involving the NF-κB and PI3
kinase pathways},
journal = {Glia},
year = {2006},
volume = {54},
pages = {775--785},
number = {8},
abstract = {Abstract 10.1002/glia.20418.abs Toll-like receptor 3 (TLR3) is a component
of the innate immune response that responds to dsRNA viruses and
virus replication intermediates. In this study we show that activation
of astrocytes with the dsRNA mimetic polyinosinic-cytidylic acid
(pI:C) results in loss of expression of connexin43 (Cx43) mRNA and
protein while upregulating the expression of the ionotropic P2 receptor
P2X4R. Analysis of the signaling pathways involved failed to demonstrate
a role for the p38 MAP kinase, ERK, or JNK signaling pathways whereas
an inhibitor of the PI3 kinase/Akt pathway effectively blocked the
action of pI:C. Using adenoviral vectors containing a super-repressor
of NF-κB (NF-κB SR) construct or a dominant negative interferon
regulatory factor 3 (dnIRF3) construct showed that inhibition of
both transcription factors also blocked the effects of pI:C. To explore
the functional consequences of pI:C activation we used a pore-forming
assay for P2X4R activity and a scrape loading assay for gap junction
intercellular communication (GJIC). No pore-forming activity consistent
with functional P2X4R expression was detected in either control or
activated astrocytes. In contrast, robust Lucifer yellow transfer
indicative of GJIC was detected in resting cells that was lost following
pI:C activation. The dnIRF3 construct failed to restore GJIC whereas
the NF-κB SR or the NF-κB inhibitor BAY11-7082 and the PI3K inhibitor
LY294002 all significantly reversed the effect of pI:C on GJ connectivity.
We conclude that activation of the innate immune response in astrocytes
is associated with functional loss of GJIC through a pathway involving
NF-κB and PI3 kinase. © 2006 Wiley-Liss, Inc.},
issn = {1098-1136},
keywords = {CNS glia, innate immunity, gap junctions},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/glia.20418}
}
@ARTICLE{Zhao2009e,
author = {Zhao, Yuan and Zhou, Tianhua and Li, Aiqing and Yao, Haomi and He,
Fei and Wang, Liangjing and Si, Jianmin},
title = {A Potential Role of Collagens Expression in Distinguishing Between
Premalignant and Malignant Lesions in Stomach},
journal = {Anat Rec},
year = {2009},
volume = {292},
pages = {692--700},
number = {5},
abstract = {Abstract 10.1002/ar.20874.abs Lack of clinical biomarkers for early
gastric cancer without specific early symptoms leads to delayed diagnosis,
which contributes to high mortality of gastric cancer. Here, we used
oligonucleotide microarray to systematically examine differential
gene expression among 33 samples from normal, premalignant, and malignant
lesions in stomach. A focal adhesion pathway mainly composed of collagen
genes was found to have a significantly different expression profile
in gastric cancers compared to premalignant lesions. A subset of
collagen genes efficiently separated malignant from premalignant
tissues, and two representative genes COL11A1 and COL1A1 were validated
in 42 tissue samples with quantitative reverse transcription-PCR
and in situ hybridization. The data above suggest that focal adhesion
pathway may have a role in the pathogenesis of gastric cancer, and
the expression profile of collagen genes may be a potential biomarker
to distinguish malignant from premalignant lesions in stomach. Anat
Rec, 2009. © 2009 Wiley-Liss, Inc.},
issn = {1932-8494},
keywords = {gastric cancer, oligonucleotide microarray, collagen, classifier,
biomarker, gene expression profiling},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ar.20874}
}
@ARTICLE{Zhao2008c,
author = {Zhao, Zhengshan and Peytavi, Regis and Diaz-Quijada, Gerardo A. and
Picard, Francois J. and Huletsky, Ann and Leblanc, Eric and Frenette,
Johanne and Boivin, Guy and Veres, Teodor and Dumoulin, Michel M.
and Bergeron, Michel G.},
title = {Plastic Polymers for Efficient DNA Microarray Hybridization: Application
to Microbiological Diagnostics},
journal = {J. Clin. Microbiol.},
year = {2008},
volume = {46},
pages = {3752--3758},
number = {11},
month = nov,
abstract = {Fabrication of microarray devices using traditional glass slides is
not easily adaptable to integration into microfluidic systems. There
is thus a need for the development of polymeric materials showing
a high hybridization signal-to-background ratio, enabling sensitive
detection of microbial pathogens. We have developed such plastic
supports suitable for highly sensitive DNA microarray hybridizations.
The proof of concept of this microarray technology was done through
the detection of four human respiratory viruses that were amplified
and labeled with a fluorescent dye via a sensitive reverse transcriptase
PCR (RT-PCR) assay. The performance of the microarray hybridization
with plastic supports made of PMMA [poly(methylmethacrylate)]-VSUVT
or Zeonor 1060R was compared to that with high-quality glass slide
microarrays by using both passive and microfluidic hybridization
systems. Specific hybridization signal-to-background ratios comparable
to that obtained with high-quality commercial glass slides were achieved
with both polymeric substrates. Microarray hybridizations demonstrated
an analytical sensitivity equivalent to approximately 100 viral genome
copies per RT-PCR, which is at least 100-fold higher than the sensitivities
of previously reported DNA hybridizations on plastic supports. Testing
of these plastic polymers using a microfluidic microarray hybridization
platform also showed results that were comparable to those with glass
supports. In conclusion, PMMA-VSUVT and Zeonor 1060R are both suitable
for highly sensitive microarray hybridizations.},
url = {http://jcm.asm.org/cgi/content/abstract/46/11/3752}
}
@ARTICLE{Zhdanova2011,
author = {Zhdanova, Olga and Srivastava, Shekhar and Di, Lie and Li, Zhai and
Tchelebi, Leila and Dworkin, Sara and Johnstone, Duncan B and Zavadil,
Jiri and Chong, Mark M and Littman, Dan R and Holzman, Lawrence B
and Barisoni, Laura and Skolnik, Edward Y},
title = {The inducible deletion of Drosha and microRNAs in mature podocytes
results in a collapsing glomerulopathy},
journal = {Kidney Int},
year = {2011},
pages = {--},
month = may,
issn = {1523-1755},
publisher = {International Society of Nephrology},
url = {http://dx.doi.org/10.1038/ki.2011.122}
}
@ARTICLE{Zhelev2005,
author = {Zhelev, Zhivko and Bakalova, Rumiana and Ewis, Ashraf and Ohba, Hideki
and Ishikawa, Mitsuru and Baba, Yoshinobu},
title = {Nonradioactive telomerase activity assay by microchip electrophoresis:
Privileges to the classical gel electrophoresis assay},
journal = {ELECTROPHORESIS},
year = {2005},
volume = {26},
pages = {3021--3024},
number = {15},
abstract = {Abstract 10.1002/elps.200410435.abs The present study accents on the
privileges of microchip-based electrophoresis to the conventional
gel electrophoresis in separation of telomerase repeat amplification
protocol/polymerase chain reaction (PCR) ladder products obtained
in telomerase-catalyzed reaction in cancer cells. We try to clarify
the interpretation of the results obtained by both electrophoretic
procedures and to avoid misinterpretation as a result of PCR-dependent
artefacts.},
issn = {1522-2683},
keywords = {Leukemia cells, Microchip electrophoresis, Miniaturization, Telomerase
activity},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/elps.200410435}
}
@ARTICLE{Zhen2007,
author = {Zhen, Eugene Y. and Berna, Michael J. and Jin, Zhaoyan and Pritt,
Michael L. and Watson, David E. and Ackermann, Bradley L. and Hale,
John E.},
title = {Quantification of heart fatty acid binding protein as a biomarker
for drug-induced cardiac and musculoskeletal necroses},
journal = {Prot. Clin. Appl.},
year = {2007},
volume = {1},
pages = {661--671},
number = {7},
abstract = {Abstract 10.1002/prca.200700006.abs Heart fatty acid binding protein
(Fabp3) is a cytosolic protein expressed primarily in heart, and
to a lesser extent in skeletal muscle, brain, and kidney. During
myocardial injury, the Fabp3 level in serum is elevated rapidly,
making it an ideal early marker for myocardial infarction. In this
study, an MS-based selected reaction monitoring method (LC-SRM) was
developed for quantifying Fabp3 in rat serum. Fabp3 was enriched
first through an immobilized antibody, and the protein was digested
on beads directly. A marker peptide of Fabp3 was quantified using
LC-SRM with a stable isotope-labeled peptide standard. For six quality
control samples with Fabp3 ranging from 0.256 to 25 ng, the average
recovery following the procedure was about 73%, and the precision
(%CV) between replicates was less than 7%. The Fabp3 concentrations
in rat serum peaked 1 h after isoproterenol treatment, and returned
to baseline levels 24 h after the dose. Elevated Fabp3 levels were
also detected in rats administered with a PPAR α/δ agonist, which
has shown to cause skeletal muscle necrosis. Fabp3 can be used as
a biomarker for both cardiac and skeletal necroses. The cross-validation
of the LC-SRM method with an existing ELISA method is described.},
issn = {1862-8354},
keywords = {Biomarker, Cardiac toxicity, Heart fatty acid binding protein, LC-SRM},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/prca.200700006}
}
@ARTICLE{Zhen2007a,
author = {Zhen, Guohua and Park, Sung Woo and Nguyenvu, Louis T. and Rodriguez,
Madeleine W. and Barbeau, Rebecca and Paquet, Agnes C. and Erle,
David J.},
title = {IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct
Roles in Epithelial Cell Mucin Production},
journal = {Am. J. Respir. Cell Mol. Biol.},
year = {2007},
volume = {36},
pages = {244--253},
number = {2},
month = feb,
abstract = {Overproduction of mucus is a central feature of asthma. The cytokine,
IL-13, epidermal growth factor receptor (EGFR), and transcription
factor, FOXA2, have each been implicated in mucus production, but
the mechanistic relationships between these molecules are not yet
well understood. To address this, we established a primary normal
human bronchial epithelial cell culture system with IL-13-induced
mucus production and gene transcript expression changes similar to
those seen in vivo in mice. IL-13 did not stimulate release of the
EGFR ligand, transforming growth factor (TGF)-{alpha}. However, there
was constitutive release of TGF-{alpha} from normal human bronchial
epithelial cells, and inhibition of TGF-{alpha} or EGFR reduced both
constitutive and IL-13-induced mucin production. Microarray analysis
revealed that IL-13 and the EGFR pathway appear to have almost completely
independent effects on transcript expression. IL-13 induced a relatively
small set of transcripts, including several novel transcripts that
might play a role in pathogenesis of allergic airway disease. In
contrast, EGFR activity had extensive effects, including altered
expression of many transcripts associated with cell metabolism, survival,
transcription, and differentiation. One of the few common effects
of IL-13 and EGFR signaling was decreased expression of FOXA2, which
is known to prevent mucus production. We conclude that the IL-13
and EGFR pathways make critical but quite distinct contributions
to gene regulation in airway epithelial cells, and that both pathways
affect expression of the key transcription factor, FOXA2, a known
regulator of mucus production.},
url = {http://ajrcmb.atsjournals.org/cgi/content/abstract/36/2/244}
}
@ARTICLE{Zheng2010b,
author = {Zheng, Bin and Liao, Zhixiang and Locascio, Joseph J. and Lesniak,
Kristen A. and Roderick, Sarah S. and Watt, Marla L. and Eklund,
Aron C. and Zhang-James, Yanli and Kim, Peter D. and Hauser, Michael
A. and Grunblatt, Edna and Moran, Linda B. and Mandel, Silvia A.
and Riederer, Peter and Miller, Renee M. and Federoff, Howard J.
and Wullner, Ullrich and Papapetropoulos, Spyridon and Youdim, Moussa
B. and Cantuti-Castelvetri, Ippolita and Young, Anne B. and Vance,
Jeffery M. and Davis, Richard L. and Hedreen, John C. and Adler,
Charles H. and Beach, Thomas G. and Graeber, Manuel B. and Middleton,
Frank A. and Rochet, Jean-Christophe and Scherzer, Clemens R. and
the Global PD Gene Expression (GPEX) Consortium},
title = {PGC-1{alpha}, A Potential Therapeutic Target for Early Intervention
in Parkinson's Disease},
journal = {Science Translational Medicine},
year = {2010},
volume = {2},
pages = {52ra73--},
number = {52},
month = oct,
abstract = {Parkinson's disease affects 5 million people worldwide, but the molecular
mechanisms underlying its pathogenesis are still unclear. Here, we
report a genome-wide meta-analysis of gene sets (groups of genes
that encode the same biological pathway or process) in 410 samples
from patients with symptomatic Parkinson's and subclinical disease
and healthy controls. We analyzed 6.8 million raw data points from
nine genome-wide expression studies, and 185 laser-captured human
dopaminergic neuron and substantia nigra transcriptomes, followed
by two-stage replication on three platforms. We found 10 gene sets
with previously unknown associations with Parkinson's disease. These
gene sets pinpoint defects in mitochondrial electron transport, glucose
utilization, and glucose sensing and reveal that they occur early
in disease pathogenesis. Genes controlling cellular bioenergetics
that are expressed in response to peroxisome proliferator-activated
receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) are underexpressed
in Parkinson's disease patients. Activation of PGC-1{alpha} results
in increased expression of nuclear-encoded subunits of the mitochondrial
respiratory chain and blocks the dopaminergic neuron loss induced
by mutant {alpha}-synuclein or the pesticide rotenone in cellular
disease models. Our systems biology analysis of Parkinson's disease
identifies PGC-1{alpha} as a potential therapeutic target for early
intervention.},
url = {http://stm.sciencemag.org/cgi/content/abstract/2/52/52ra73}
}
@ARTICLE{Zheng2004,
author = {Zheng, Dongling and Constantinidou, Chrystala and Hobman, Jon L.
and Minchin, Stephen D.},
title = {Identification of the CRP regulon using in vitro and in vivo transcriptional
profiling},
journal = {Nucleic Acids Res.},
year = {2004},
volume = {32},
pages = {5874--5893},
number = {19},
month = nov,
abstract = {The Escherichia coli cyclic AMP receptor protein (CRP) is a global
regulator that controls transcription initiation from more than 100
promoters by binding to a specific DNA sequence within cognate promoters.
Many genes in the CRP regulon have been predicted simply based on
the presence of DNA-binding sites within gene promoters. In this
study, we have exploited a newly developed technique, run-off transcription/microarray
analysis (ROMA) to define CRP-regulated promoters. Using ROMA, we
identified 176 operons that were activated by CRP in vitro and 16
operons that were repressed. Using positive control mutants in different
regions of CRP, we were able to classify the different promoters
into class I or class II/III. A total of 104 operons were predicted
to contain Class II CRP-binding sites. Sequence analysis of the operons
that were repressed by CRP revealed different mechanisms for CRP
inhibition. In contrast, the in vivo transcriptional profiles failed
to identify most CRP-dependent regulation because of the complexity
of the regulatory network. Analysis of these operons supports the
hypothesis that CRP is not only a regulator of genes required for
catabolism of sugars other than glucose, but also regulates the expression
of a large number of other genes in E.coli. ROMA has revealed 152
hitherto unknown CRP regulons.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/32/19/5874}
}
@ARTICLE{Zheng2008,
author = {Zheng, Dongling and Feeney, Graham P. and Kille, Peter and Hogstrand,
Christer},
title = {Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc
repression of ZIP10 transcription by an intronic MRE cluster},
journal = {Physiol Genomics},
year = {2008},
volume = {34},
pages = {205--214},
number = {2},
month = jul,
abstract = {Resolving the mechanisms underlying the temporal and spatial profile
of zinc transporter expression in response to zinc availability is
key to understanding zinc homeostasis. The mRNA expression of seven
zinc transporters was studied in zebrafish gills when treated with
zinc deficiency/excess over a 14-day period. Of these, ZnT1, ZnT5,
ZIP3, and ZIP10 were differentially expressed in response to changed
zinc status. The mRNA level of zinc exporter, ZnT1, was upregulated
in fish subjected to excess zinc and downregulated by zinc deprivation.
This response was similar to that of metallothionein-2 (MT2). Zinc
deficiency caused an increased abundance of mRNA for zinc importers
ZnT5, ZIP3, and ZIP10. Expression of ZnT5 and ZIP10, but not ZIP3,
was inhibited by excess zinc. Zinc influx function of ZIP10 was demonstrated
by 65Zn transport assays in Xenopus oocyte expression experiments,
suggesting that the inverse relationship between zinc availability
and ZIP10 expression serves to maintain zinc homeostasis. Two distinct
transcription start sites (TSS) for ZIP10 were found in gill and
kidney. Luciferase assays and mutation/deletion analysis of DNA fragments
proximal to the respective TSS revealed that ZIP10 has two alternative
promoters (P1 and P2) displaying opposite regulatory control in response
to zinc status. Positive as well as negative regulation by zinc involves
MRE clusters in the respective promoters. These results provide experimental
evidence for MREs functioning as repressor elements, implicating
MTF1 involvement in the negative regulation of ZIP10. This is in
contrast to the well-established positive regulation by MTF1 of other
genes, such as MT2 and ZnT1.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/34/2/205}
}
@ARTICLE{Zheng2010c,
author = {Zheng, Dongling and Kille, Peter and Feeney, Graham and Cunningham,
Phil and Handy, Richard and Hogstrand, Christer},
title = {Dynamic transcriptomic profiles of zebrafish gills in response to
zinc depletion},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {548},
number = {1},
abstract = {BACKGROUND:Zinc deficiency is detrimental to organisms, highlighting
its role as an essential micronutrient contributing to numerous biological
processes. To investigate the underlying molecular events invoked
by zinc depletion we performed a temporal analysis of transcriptome
changes observed within the zebrafish gill. This tissue represents
a model system for studying ion absorption across polarised epithelial
cells as it provides a major pathway for fish to acquire zinc directly
from water whilst sharing a conserved zinc transporting system with
mammals.RESULTS:Zebrafish were treated with either zinc-depleted
(water = 2.61 µg L-1; diet = 26 mg kg-1) or zinc-adequate (water
= 16.3 µg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill
samples were collected at five time points and transcriptome changes
analysed in quintuplicate using a 16K oligonucleotide array. Of the
genes represented the expression of a total of 333 transcripts showed
differential regulation by zinc depletion (having a fold-change greater
than 1.8 and an adjusted P-value less than 0.1, controlling for a
10% False Discovery Rate). Down-regulation was dominant at most time
points and distinct sets of genes were regulated at different stages.
Annotation enrichment analysis revealed that 'Developmental Process'
was the most significantly overrepresented Biological Process GO
term (P = 0.0006), involving 26% of all regulated genes. There was
also significant bias for annotations relating to development, cell
cycle, cell differentiation, gene regulation, butanoate metabolism,
lysine degradation, protein tyrosin phosphatases, nucleobase, nucleoside
and nucleotide metabolism, and cellular metabolic processes. Within
these groupings genes associated with diabetes, bone/cartilage development,
and ionocyte proliferation were especially notable. Network analysis
of the temporal expression profile indicated that transcription factors
foxl1, wt1, nr5a1, nr6a1, and especially, hnf4a may be key coordinators
of the homeostatic response to zinc depletion.CONCLUSIONS:The study
revealed the complex regulatory pathways that allow the organism
to subtly respond to the low-zinc condition. Many of the processes
affected reflected a fundamental restructuring of the gill epithelium
through reactivation of developmental programs leading to stem cell
differentiation. The specific regulation of genes known to be involved
in development of diabetes provides new molecular links between zinc
deficiency and this disease. The present study demonstrates the importance
of including the time-dimension in microarray studies.},
doi = {10.1186/1471-2164-11-548},
issn = {1471-2164},
pubmedid = {20932299},
url = {http://www.biomedcentral.com/1471-2164/11/548}
}
@ARTICLE{Zheng2004a,
author = {Zheng, Feng and Cheng, Qing-Li and Plati, Anna-Rita and Ye, Shui
Qin and Berho, Mariana and Banerjee, Anita and Potier, Mylene and
Jaimes, Edgar A. and Yu, Hong and Guan, You-Fei and Hao, Chung-Ming
and Striker, Liliane J. and Striker, Gary E.},
title = {The Glomerulosclerosis of Aging in Females: Contribution of the Proinflammatory
Mesangial Cell Phenotype to Macrophage Infiltration},
journal = {Am. J. Pathol.},
year = {2004},
volume = {165},
pages = {1789--1798},
number = {5},
month = nov,
abstract = {Age-associated renal changes may be an important cause of renal failure.
We recently found that aged female B6 mice developed progressive
glomerular lesions. This was associated with macrophage infiltration,
a frequent finding in glomerulosclerosis. We used these mice as a
model for studying the mechanisms of glomerular aging. We compared
the gene expression profile of intact glomeruli from late postmenopausal
(28-month-old) mice to that of intact glomeruli from premenopausal
(5-month-old) mice. We found that inflammation-related genes, especially
those expressed by activated macrophages, were up-regulated in the
glomeruli of 28-month-old mice, a result correlating with the histological
observation of glomerular macrophage infiltration. The mechanism
for macrophage recruitment could have been stable phenotypic changes
in mesangial cells because we found that mesangial cells isolated
from 28-month-old mice expressed higher levels of RANTES and VCAM-1
than cells from 5-month-old mice. The elevated serum tumor necrosis
factor (TNF)-{alpha} levels present in aged mice may contribute to
increased RANTES and VCAM-1 expression in mesangial cells. Furthermore,
cells from 28-month-old mice were more sensitive to TNF-{alpha}-induced
RANTES and VCAM-1 up-regulation. The effect of TNF-{alpha} on RANTES
expression was mediated by TNF receptor 1. Interestingly, mesangial
cells isolated from 28-month-old mice had increased nuclear factor-{kappa}B
transcriptional activity. Inhibition of nuclear factor-{kappa}B activity
decreased baseline as well as TNF-{alpha}-induced RANTES and VCAM-1
expression in mesangial cells isolated from 28-month-old mice. Thus,
phenotypic changes in mesangial cells may predispose them to inflammatory
stimuli, such as TNF-{alpha}, which would contribute to glomerular
macrophage infiltration and inflammatory lesions in aging.},
url = {http://ajp.amjpathol.org/cgi/content/abstract/165/5/1789}
}
@ARTICLE{Zheng2006,
author = {Zheng, Jiamao and Watson, Anjanette D. and Kerr, David E.},
title = {Genome-Wide Expression Analysis of Lipopolysaccharide-Induced Mastitis
in a Mouse Model},
journal = {Infect. Immun.},
year = {2006},
volume = {74},
pages = {1907--1915},
number = {3},
month = mar,
abstract = {To better understand the acute host response to Escherichia coli mastitis,
we analyzed gene expression patterns of approximately 23,000 transcripts
4 h after an intramammary infusion of lipopolysaccharide (LPS) in
a mouse model. A total of 489 genes were significantly affected,
of which 391 were induced and 98 were repressed. Gene ontology analysis
demonstrated that most of the induced genes were associated with
the innate immune response, apoptosis, and cell proliferation. Substantial
induction of the chemokines CXCL1, CXCL2, and S100A8; the acute-phase
protein SAA3; and the LPS binding protein CD14 were confirmed by
Northern blot analysis. A subsequent time course experiment revealed
CXCL1 induction prior to that of CD14 and SAA3. Mammary epithelial
cell cultures also showed marked expression of these factors in response
to LPS. The expression of immune-related genes in mammary epithelial
cells indicates the importance of this cell type in initiating the
inflammatory responses. Repressed genes include several carbohydrate
and fatty acid metabolic enzymes and potassium transporters, which
may contribute to milk composition changes during mastitis. Therefore,
the overall transcription profile, in conjunction with gene ontology
analysis, provides a detailed picture of the molecular mechanisms
underlying the complex biological processes that occur during LPS-induced
mastitis.},
url = {http://iai.asm.org/cgi/content/abstract/74/3/1907}
}
@ARTICLE{Zheng2011c,
author = {Zheng, Jenny L. and Parfett, Craig and Williams, Andrew and Yagminas,
Al and Zhou, Gu and Douglas, George R. and Yauk, Carole L.},
title = {Assessment of subclinical, toxicant-induced hepatic gene expression
profiles after low-dose, short-term exposures in mice},
journal = {Regulatory Toxicology and Pharmacology},
year = {2011},
volume = {60},
pages = {54--72},
number = {1},
month = jun,
abstract = {Gene expression profiling that examines critical, toxicologically-relevant
gene and signal-response pathways promises to improve risk assessment
and safety evaluation of low-dose chemical exposures. As an approach
to achieving this goal, mechanistic interpretations based upon gene
expression changes that are determinants of adverse toxicological
outcomes were applied to the analysis of low-dose gene expression
profiles. RNA for expression profiling was obtained from mice given
short-term gavage exposures to diminishing doses of four toxicants:
3,3',4,4',5-pentachlorobiphenyl (PCB126), phenobarbital (PB), isoproterenol
(IPR), and lead acetate (PbAc). Lowest doses were below the no-observable
effects levels established using standard clinical toxicology parameters.
Hepatic gene expression profiles were analyzed using a custom, focused
oligonucleotide DNA microarray, the HC ToxArray(TM), containing toxin-responsive
and toxicologically-determinant genes. Expression data were compared
to changes in conventional clinical chemistry parameters and drug
metabolism activities. PCB126 and PB demonstrated a dose-dependent
correlation between minimal changes in biochemical markers, hepatic
metabolism and induction of gene expression profiles. PbAc exposure
gave a small adaptive profile at the highest dose. IPR- and PCB126-induced
changes were detected at doses below those required to alter the
traditional biochemical endpoints and included genes with causal
roles in hepatic toxicity, insulin resistance, atherosclerosis, angiogenesis
and hypertension. Likely adverse phenotypic consequences resulting
from expression changes lead to assignments of "Lowest Observed Adverse
Transcriptional Expression Levels" (LOATEL) for each agent. These
results support the suggestion that altered expression profiles of
genes contributing to toxicologically-relevant pathways provide useful
tools for reducing uncertainty in establishing no-effect levels and
for designing longer-term toxicity studies.},
issn = {0273-2300},
keywords = {Dose-response, RNA profiling, Toxicogenomics, Phenotypic anchoring,
Mode of action},
url = {http://www.sciencedirect.com/science/article/pii/S0273230011000328}
}
@ARTICLE{Zheng2009,
author = {Zheng, Luqing and Huang, Fangliang and Narsai, Reena and Wu, Jiaojiao
and Giraud, Estelle and He, Fei and Cheng, Longjun and Wang, Fang
and Wu, Ping and Whelan, James and Shou, Huixia},
title = {Physiological and Transcriptome Analysis of Iron and Phosphorus Interaction
in Rice Seedlings},
journal = {Plant Physiology},
year = {2009},
volume = {151},
pages = {262--274},
number = {1},
month = sep,
abstract = {The antagonistic interaction between iron (Fe) and phosphorus (P)
has been noted in the area of plant nutrition. To understand the
physiology and molecular mechanisms of this interaction, we studied
the growth performance, nutrient concentration, and gene expression
profiles of root and shoot segments derived from 10-d-old rice (Oryza
sativa) seedlings under four different nutrient conditions: (1) full
strength of Fe and P (+Fe+P); (2) full strength of P and no Fe (-Fe+P);
(3) full strength of Fe and no P (+Fe-P); and (4) without both Fe
and P (-Fe-P). While removal of Fe in the growth medium resulted
in very low shoot and root Fe concentrations, the chlorotic symptoms
and retarded seedling growth were only observed on seedlings grown
in the presence of P. Microarray data showed that in roots, 7,628
transcripts were significantly changed in abundance in the absence
of Fe alone. Interestingly, many of these changes were reversed if
P was also absent (-Fe-P), with only approximately 15% overlapping
with -Fe alone (-Fe+P). Analysis of the soluble Fe concentration
in rice seedling shoots showed that P deficiency resulted in significantly
increased Fe availability within the plants. The soluble Fe concentration
under -Fe-P conditions was similar to that under +Fe+P conditions.
These results provide evidence that the presence of P can affect
Fe availability and in turn can influence the regulation of Fe-responsive
genes.},
url = {http://www.plantphysiol.org/cgi/content/abstract/151/1/262}
}
@ARTICLE{Zheng2011,
author = {Zheng, Qun and Schaefer, Anneliese M. and Nonet, Michael L.},
title = {Regulation of C. elegans presynaptic differentiation and neurite
branching via a novel signaling pathway initiated by SAM-10},
journal = {Development},
year = {2011},
volume = {138},
pages = {87--96},
number = {1},
month = jan,
abstract = {Little is known about transcriptional control of neurite branching
or presynaptic differentiation, events that occur relatively late
in neuronal development. Using the Caenorhabditis elegans mechanosensory
circuit as an in vivo model, we show that SAM-10, an ortholog of
mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously
in the nucleus to regulate synaptic differentiation, as well as positioning
of, a single neurite branch. PLM mechanosensory neurons in sam-10
mutants exhibit abnormal placement of the neurite branch point, and
defective synaptogenesis, characterized by an overextended synaptic
varicosity, underdeveloped synaptic morphology and disrupted colocalization
of active zone and synaptic vesicles. SAM-10 functions coordinately
with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations
that: (1) mutations in either gene show similar defects in PLM neurons;
and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10
regulates PLM synaptic differentiation by suppressing transcription
of prk-2, which encodes an ortholog of the mammalian Pim kinase family.
PRK-2-mediated activities of SAM-10 are specifically involved in
PLM synaptic differentiation, but not other sam-10 phenotypes such
as neurite branching. Thus, these data reveal a novel transcriptional
signaling pathway that regulates neuronal specification of neurite
branching and presynaptic differentiation.},
comment = {10.1242/dev.055350},
url = {http://dev.biologists.org/cgi/content/abstract/138/1/87}
}
@ARTICLE{Zheng2010a,
author = {Zheng, Wei and Zhao, Xiaoping and Wang, Jie and Lu, Luo},
title = {Retinal vascular leakage occurring in GABA Rho-1 subunit deficient
mice},
journal = {Experimental Eye Research},
year = {2010},
volume = {90},
pages = {634--640},
number = {5},
month = may,
abstract = {Recent studies demonstrate that GABAergic activity elicits relaxation
of retinal arterioles leading to an increase in blood flow. It has
also been found that GABAnergic activity in the retina of mice with
diabetic retinopathy is suppressed. In this study, we provide further
evidence that lack of GABAergic activity significantly alters vasculature
development as well as the hypoxia-induced angiogenic response. Using
GABAC receptor [rho]1 subunit-knockout mice (rho-1-/-), our results
demonstrate that in hypoxia-induced retinas a severe vascular leakage
occurred in 2 week-old rho-1-/- mice compared with their wildtype
counterparts. In addition, our results also showed that all of the
rho-1-/- mice developed significant retinal vascular leakages by
48 weeks-of-age. Microarray and real-time PCR experiments revealed
a unique angiogenesis-related gene expression pattern. This suggests
that retinal vascular disorders of rho-1-/- mice results from significant
up-regulation of angiogenic genes and concomitant down-regulation
of anti-angiogenic genes. The study results are consistent with the
pathological changes of the retinal vascular leakage seen in diabetic
retinopathy. Our data indicate that the GABAC [rho]1 subunit plays
a role in maintaining both homeostasis and balance of retinal neurotransmitter
function. Knockout of the retinal GABAC [rho]1-subunit leads to changes
in vascular permeability similar to the pathological changes induced
by retinal hypoxic conditions.},
issn = {0014-4835},
keywords = {gene expression, angiogenesis, retinopathy, microarray, transgenic
animal},
url = {http://www.sciencedirect.com/science/article/B6WFD-4YH4R4G-1/2/14beba5e5ba29c70a45fdbf8c8c286cc}
}
@ARTICLE{Zheng2011b,
author = {Zheng, Xiaojing and Morrison, Alanna C. and Feingold, Eleanor and
Turner, Stephen T. and Ferrell, Robert E.},
title = {Association Between NEDD4L Gene and Sodium Lithium Countertransport},
journal = {Am J Hypertens},
year = {2011},
volume = {24},
pages = {145--148},
number = {2},
month = feb,
issn = {0895-7061},
publisher = {American Journal of Hypertension, Ltd},
url = {http://dx.doi.org/10.1038/ajh.2010.222}
}
@ARTICLE{Zheng2008a,
author = {Zheng, Yan and Kief, Jan and Auffarth, Kathrin and Farfsing, Jan
W. and Mahlert, Michael and Nieto, Fernanda and Basse, Christoph
W.},
title = {The Ustilago maydis Cys2His2-type zinc finger transcription factor
Mzr1 regulates fungal gene expression during the biotrophic growth
stage},
journal = {Molecular Microbiology},
year = {2008},
volume = {68},
pages = {1450--1470},
number = {6},
abstract = {Summary The smut fungus Ustilago maydis establishes a biotrophic relationship
with its host plant maize to progress through sexual development.
Here, we report the identification and characterization of the Cys2His2-type
zinc finger protein Mzr1 that functions as a transcriptional activator
during host colonization. Expression of the U. maydis mig2 cluster
genes is tightly linked to this phase. Upon conditional overexpression,
Mzr1 confers induction of a subset of mig2 genes during vegetative
growth and this requires the same promoter elements that confer inducible
expression in planta. Furthermore, expression of the mig2-4 and mig2-5
genes during biotrophic growth is strongly reduced in cells deleted
in mzr1. DNA-array analysis led to the identification of additional
Mzr1-induced genes. Some of these genes show a mig2-like plant-specific
expression pattern and Mzr1 is responsible for their high-level expression
during pathogenesis. Mzr1 function requires the b-dependently regulated
Cys2His2-type cell cycle regulator Biz1, indicating that two stage-specific
regulators mediate gene expression during host colonization. In spite
of a role as transcriptional activator during biotrophic growth,
mzr1 is not essential for pathogenesis; however, conditional overexpression
interfered with proliferation during vegetative growth and mating
ability, caused a cell separation defect, and triggered filamentous
growth. We discuss the implications of these findings.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2008.06244.x}
}
@ARTICLE{Zheng2010,
author = {Zheng, Zongli and Advani, Abdolreza and Melefors, Ojar and Glavas,
Steve and Nordstrom, Henrik and Ye, Weimin and Engstrand, Lars and
Andersson, Anders F.},
title = {Titration-free massively parallel pyrosequencing using trace amounts
of starting material},
journal = {Nucleic Acids Res.},
year = {2010},
volume = {38},
pages = {e137--},
number = {13},
month = jul,
abstract = {Continuous efforts have been made to improve next-generation sequencing
methods for increased robustness and for applications on low amounts
of starting material. We applied double-stranded library protocols
for the Roche 454 platform to avoid the yield-reducing steps associated
with single-stranded library preparation, and applied a highly sensitive
Taqman MGB-probe-based quantitative polymerase chain reaction (qPCR)
method. The MGB-probe qPCR, which can detect as low as 100 copies,
was used to quantify the amount of effective library, i.e. molecules
that form functional clones in emulsion PCR. We also demonstrate
that the distribution of library molecules on capture beads follows
a Poisson distribution. Combining the qPCR and Poisson statistics,
the labour-intensive and costly titration can be eliminated and trace
amounts of starting material such as precious clinical samples, transcriptomes
of small tissue samples and metagenomics on low biomass environments
is applicable.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/38/13/e137}
}
@ARTICLE{Zheng2011a,
author = {Zheng, Zhengui and Cohn, Martin J.},
title = {From the Cover: Developmental basis of sexually dimorphic digit ratios},
journal = {PNAS},
year = {2011},
volume = {108},
pages = {16289-16294},
number = {39},
abstract = {Males and females generally have different finger proportions. In
males, digit 2 is shorter than digit 4, but in females digit 2 is
the same length or longer than digit 4. The second- to fourth-digit
(2D:4D) ratio correlates with numerous sexually dimorphic behavioral
and physiological conditions. Although correlational studies suggest
that digit ratios reflect prenatal exposure to androgen, the developmental
mechanism underlying sexually dimorphic digit development remains
unknown. Here we report that the 2D:4D ratio in mice is controlled
by the balance of androgen to estrogen signaling during a narrow
window of digit development. Androgen receptor (AR) and estrogen
receptor (ER-) activity is higher in digit 4 than in digit 2. Inactivation
of AR decreases growth of digit 4, which causes a higher 2D:4D ratio,
whereas inactivation of ER- increases growth of digit 4, which leads
to a lower 2D:4D ratio. We also show that addition of androgen has
the same effect as inactivation of ER and that addition of estrogen
mimics the reduction of AR. Androgen and estrogen differentially
regulate the network of genes that controls chondrocyte proliferation,
leading to differential growth of digit 4 in males and females. These
studies identify previously undescribed molecular dimorphisms between
male and female limb buds and provide experimental evidence that
the digit ratio is a lifelong signature of prenatal hormonal exposure.
Our results also suggest that the 2D:4D ratio can serve as an indicator
of disrupted endocrine signaling during early development, which
may aid in the identification of fetal origins of adult diseases.},
doi = {10.1073/pnas.1108312108},
eprint = {http://www.pnas.org/cgi/reprint/108/39/16289.pdf},
url = {http://www.pnas.org/cgi/content/abstract/108/39/16289}
}
@ARTICLE{Zhong2011a,
author = {Zhong, Silin and Joung, Je-Gun and Zheng, Yi and Chen, Yun-ru and
Liu, Bao and Shao, Ying and Xiang, Jenny Z. and Fei, Zhangjun and
Giovannoni, James J.},
title = {High-Throughput Illumina Strand-Specific RNA Sequencing Library Preparation},
journal = {Cold Spring Harb Protoc},
year = {2011},
volume = {2011},
pages = {pdb.prot5652},
number = {8},
abstract = {Conventional Illumina RNA-Seq does not have the resolution to decode
the complex eukaryote transcriptome due to the lack of RNA polarity
information. Strand-specific RNA sequencing (ssRNA-Seq) can overcome
these limitations and as such is better suited for genome annotation,
de novo transcriptome assembly, and accurate digital gene expression
analysis. This protocol describes a simple and robust method to generate
ssRNA-Seq libraries for the Illumina sequencing platform. It has
significantly increased the throughput to 96 libraries in a two-day
preparation while simultaneously lowering the reagent costs to below
ten dollars per library. It is compatible with both single-read and
paired-end multiplex sequencing and, most importantly, its data can
also be used with existing conventional RNA-Seq data. This is a significant
advantage, because it enables researchers to switch to ssRNA-Seq
even if a large amount of data has already been generated by the
nonstrand specific methods.},
doi = {10.1101/pdb.prot5652},
eprint = {http://cshprotocols.cshlp.org/cgi/reprint/2011/8/pdb.prot5652.pdf},
url = {http://cshprotocols.cshlp.org/cgi/content/abstract/2011/8/pdb.prot5652}
}
@ARTICLE{Zhong2008,
author = {Zhong, Silin and Li, Hongying and Bodi, Zsuzsanna and Button, James
and Vespa, Laurent and Herzog, Michel and Fray, Rupert G.},
title = {MTA Is an Arabidopsis Messenger RNA Adenosine Methylase and Interacts
with a Homolog of a Sex-Specific Splicing Factor},
journal = {PLANT CELL},
year = {2008},
volume = {20},
pages = {1278--1288},
number = {5},
month = may,
abstract = {N6-Methyladenosine is a ubiquitous modification identified in the
mRNA of numerous eukaryotes, where it is present within both coding
and noncoding regions. However, this base modification does not alter
the coding capacity, and its biological significance remains unclear.
We show that Arabidopsis thaliana mRNA contains N6-methyladenosine
at levels similar to those previously reported for animal cells.
We further show that inactivation of the Arabidopsis ortholog of
the yeast and human mRNA adenosine methylase (MTA) results in failure
of the developing embryo to progress past the globular stage. We
also demonstrate that the arrested seeds are deficient in mRNAs containing
N6-methyladenosine. Expression of MTA is strongly associated with
dividing tissues, particularly reproductive organs, shoot meristems,
and emerging lateral roots. Finally, we show that MTA interacts in
vitro and in vivo with At FIP37, a homolog of the Drosophila protein
FEMALE LETHAL2D and of human WILMS' TUMOUR1-ASSOCIATING PROTEIN.
The results reported here provide direct evidence for an essential
function for N6-methyladenosine in a multicellular eukaryote, and
the interaction with At FIP37 suggests possible RNA processing events
that might be regulated or altered by this base modification.},
url = {http://www.plantcell.org/cgi/content/abstract/20/5/1278}
}
@ARTICLE{Zhong2011,
author = {Zhong, Xiang and Chung, Arthur C.K. and Chen, Hai-Yong and Meng,
Xiao-Ming and Lan, Hui Y.},
title = {Smad3-Mediated Upregulation of miR-21 Promotes Renal Fibrosis},
journal = {J. Am. Soc. Nephrol.},
year = {2011},
volume = {22},
pages = {1668-1681},
number = {9},
abstract = {TGF-{beta}/Smad signaling plays a role in fibrogenesis, but therapies
targeting TGF-{beta} are ineffective in treating renal fibrosis.
Here, we explored the therapeutic potential of targeting TGF-{beta}-induced
microRNA in the progression of renal fibrosis. Microarray analysis
and real-time PCR revealed upregulation of miR-21 in tubular epithelial
cells (TECs) in response to TGF-{beta}. Lack of Smad3, but not lack
of Smad2, prevented cells from upregulating miR-21 in response to
TGF-{beta}. In addition, Smad3-deficient mice were protected from
upregulation of miR-21 and fibrosis in the unilateral ureteral obstruction
model. In contrast, conditional knockout of Smad2 enhanced miR-21
expression and renal fibrosis. Furthermore, ultrasound-microbubble-mediated
gene transfer of a miR-21-knockdown plasmid halted the progression
of renal fibrosis in established obstructive nephropathy. In conclusion,
these data demonstrate that Smad3, but not Smad2, signaling increases
expression of miR-21, which promotes renal fibrosis. Inhibition of
miR-21 may be a therapeutic approach to suppress renal fibrosis.},
doi = {10.1681/ASN.2010111168},
eprint = {http://jasn.asnjournals.org/cgi/reprint/22/9/1668.pdf},
url = {http://jasn.asnjournals.org/cgi/content/abstract/22/9/1668}
}
@ARTICLE{Zhou2008,
author = {Zhou, Dan and Wang, Jiyi and Zapala, Matthew A. and Xue, Jin and
Schork, Nicholas J. and Haddad, Gabriel G.},
title = {Gene expression in mouse brain following chronic hypoxia: role of
sarcospan in glial cell death},
journal = {Physiol Genomics},
year = {2008},
volume = {32},
pages = {370--379},
number = {3},
month = feb,
abstract = {Hypoxia is a hallmark of respiratory, neurological, or hematological
diseases as well as life at high altitude. For example, chronic constant
hypoxia (CCH) occurs in chronic lung diseases or at high altitude,
whereas chronic intermittent hypoxia (CIH) occurs in diseases such
as sleep apnea or sickle cell disease. Despite the fact that such
conditions are frequent, the cellular and molecular mechanisms underlying
the effect of hypoxia, whether constant or intermittent, are not
well understood. In this study, we first determined the effect of
CCH and CIH on global gene expression in different regions of mouse
brain using microarrays and then investigated the biological role
of genes of interest. We found that: 1) in the cortical region, the
expression level of 80 genes was significantly altered by CIH (16
up- and 64 downregulated), and this number increased to 137 genes
following CCH (34 up- and 103 downregulated); 2) a similar number
of gene alterations was identified in the hippocampal area, and the
majority of the changes in this region were upregulations; 3) two
genes (Sspn and Ttc27) were downregulated in both brain regions and
following both treatments; and 4) RNA interference-mediated knockdown
of Sspn increased cell death in hypoxia in a cell culture system.
We conclude that CIH or CCH induced significant and distinguishable
alterations in gene expression in cortex and hippocampus and that
Sspn seems to play a critical role in inducing cell death under hypoxic
conditions.},
url = {http://physiolgenomics.physiology.org/cgi/content/abstract/32/3/370}
}
@ARTICLE{Zhou2011b,
author = {Zhou, Feng and Zhao, Qianqian and Liu, Yunlong and Goodlett, Charles
and Liang, Tiebing and McClintick, Jeanette and Edenberg, Howard
and Li, Lang},
title = {Alteration of gene expression by alcohol exposure at early neurulation},
journal = {BMC Genomics},
year = {2011},
volume = {12},
pages = {124},
number = {1},
abstract = {BACKGROUND:We have previously demonstrated that alcohol exposure at
early neurulation induces growth retardation, neural tube abnormalities,
and alteration of DNA methylation. To explore the global gene expression
changes which may underline these developmental defects, microarray
analyses were performed in a whole embryo mouse culture model that
allows control over alcohol and embryonic variables.RESULT:Alcohol
caused teratogenesis in brain, heart, forelimb, and optic vesicle;
a subset of the embryos also showed cranial neural tube defects.
In microarray analysis (accession number GSM9545), adopting hypothesis-driven
Gene Set Enrichment Analysis (GSEA) informatics and intersection
analysis of two independent experiments, we found that there was
a collective reduction in expression of neural specification genes
(neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1,
Klf10 (Tieg), and Edil3], and alteration of genes involved in cell
growth, apoptosis, histone variants, eye and heart development. There
was also a reduction of retinol binding protein 1 (Rbp1), and de
novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably,
four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin,
and ceruloplasmin) were absent after alcohol treatment, and histone
variant genes were reduced. The down-regulation of the neurospecification
and the neurotrophic genes were further confirmed by quantitative
RT-PCR. Furthermore, the gene expression profile demonstrated distinct
subgroups which corresponded with two distinct alcohol-related neural
tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC).
Further, the epidermal growth factor signaling pathway and histone
variants were specifically altered in ALC-NTO, and a greater number
of neurotrophic/growth factor genes were down-regulated in the ALC-NTO
than in the ALC-NTC embryos.CONCLUSION:This study revealed a set
of genes vulnerable to alcohol exposure and genes that were associated
with neural tube defects during early neurulation.},
doi = {10.1186/1471-2164-12-124},
issn = {1471-2164},
pubmedid = {21338521},
url = {http://www.biomedcentral.com/1471-2164/12/124}
}
@ARTICLE{Zhou2011a,
author = {Zhou, Jianbiao and Bi, Chonglei and Cheong, Lip-Lee and Mahara, Sylvia
and Liu, Shaw-Cheng and Tay, Kian-Ghee and Koh, Tze-Loong and Yu,
Qiang and Chng, Wee-Joo},
title = {The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP,
increases ROS production, and targets leukemia cells in AML},
journal = {Blood},
year = {2011},
volume = {118},
pages = {2830-2839},
number = {10},
abstract = {Recent studies have shown that 3-Deazaneplanocin A (DZNep), a histone
methyltransferase inhibitor, disrupts polycomb-repressive complex
2 (PRC2), and preferentially induces apoptosis in cancer cells, including
acute myeloid leukemia (AML). However, the underlying molecular mechanisms
are not well understood. The present study demonstrates that DZNep
induces robust apoptosis in AML cell lines, primary cells, and targets
CD34+CD38- leukemia stem cell (LSC)-enriched subpopulations. Using
RNA interference (RNAi), gene expression profiling, and ChIP, we
identified that TXNIP, a major redox control molecule, plays a crucial
role in DZNep-induced apoptosis. We show that disruption of PRC2,
either by DZNep treatment or EZH2 knockdown, reactivates TXNIP, inhibits
thioredoxin activity, and increases reactive oxygen species (ROS),
leading to apoptosis. Furthermore, we show that TXNIP is down-regulated
in AML and is a direct target of PRC2-mediated gene silencing. Consistent
with the ROS accumulation on DZNep treatment, we also see a signature
of endoplasmic reticulum (ER) stress-regulated genes, commonly associated
with cell survival, down-regulated by DZNep. Taken together, we uncover
a novel molecular mechanism of DZNep-mediated apoptosis and propose
that EZH2 may be a potential new target for epigenetic treatment
in AML.},
doi = {10.1182/blood-2010-07-294827},
eprint = {http://bloodjournal.hematologylibrary.org/cgi/reprint/118/10/2830.pdf},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/118/10/2830}
}
@ARTICLE{Zhou2006,
author = {Zhou, Jie and Rappaport, Eric F. and Tobias, John W. and Young, Terri
L.},
title = {Differential Gene Expression in Mouse Sclera during Ocular Development},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2006},
volume = {47},
pages = {1794--1802},
number = {5},
month = may,
abstract = {PURPOSE. Ocular development involves changes in extracellular matrix
components of the scleral wall as it expands. This study was conducted
to determine scleral gene expression profiles during mouse ocular
development to identify genes involved in normal scleral growth.
METHODS. Sample sets of pooled sclerae of 3- and 8-week-old mice
were microdissected, and total RNA was isolated. After reverse transcription,
the cDNA was in vitro transcribed to produce biotin-labeled cRNA.
The purified biotin-labeled cRNA samples were hybridized to microarray
chips (GeneChip Mouse Genome 430 2.0; Affymetrix, Santa Clara, CA).
Gene transcript expression profiles were determined, and eight differentially
expressed genes between the two age groups underwent further confirmation
by real-time PCR analysis. RESULTS. Differential regulation of 4884
gene transcripts in mouse sclera with less than 5% false-discovery
rate (FDR) was identified. The top 1000 with the lowest FDR among
the 4884 probe sets were filtered for threefold changes between the
two age groups, and 718 gene transcripts were identified. Among these
718 gene transcripts, 210 were upregulated and 508 downregulated
in adult relative to juvenile mouse sclera. TGF-{beta}1 and several
collagen genes were significantly downregulated. Microarray differential
expression by real-time PCR validation of eight extracellular matrix-associated
gene transcripts was confirmed. CONCLUSIONS. This is the first study
to demonstrate gene expression profiles in mouse sclera during ocular
growth. These findings support the role of TGF{beta}1 as a signaling
molecule in modulating extracellular matrix during ocular development.
This endeavor may be helpful in furthering understanding of how scleral
remodeling is regulated during eye growth.},
url = {http://www.iovs.org/cgi/content/abstract/47/5/1794}
}
@ARTICLE{Zhou2009,
author = {Zhou, Lecong and Mideros, Santiago and Bao, Lei and Hanlon, Regina
and Arredondo, Felipe and Tripathy, Sucheta and Krampis, Konstantinos
and Jerauld, Adam and Evans, Clive and St Martin, Steven and Maroof,
MA Saghai and Hoeschele, Ina and Dorrance, Anne and Tyler, Brett},
title = {Infection and genotype remodel the entire soybean transcriptome},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {49},
number = {1},
abstract = {BACKGROUND:High throughput methods, such as high density oligonucleotide
microarray measurements of mRNA levels, are popular and critical
to genome scale analysis and systems biology. However understanding
the results of these analyses and in particular understanding the
very wide range of levels of transcriptional changes observed is
still a significant challenge. Many researchers still use an arbitrary
cut off such as two-fold in order to identify changes that may be
biologically significant. We have used a very large-scale microarray
experiment involving 72 biological replicates to analyze the response
of soybean plants to infection by the pathogen Phytophthora sojae
and to analyze transcriptional modulation as a result of genotypic
variation.RESULTS:With the unprecedented level of statistical sensitivity
provided by the high degree of replication, we show unambiguously
that almost the entire plant genome (97 to 99% of all detectable
genes) undergoes transcriptional modulation in response to infection
and genetic variation. The majority of the transcriptional differences
are less than two-fold in magnitude. We show that low amplitude modulation
of gene expression (less than two-fold changes) is highly statistically
significant and consistent across biological replicates, even for
modulations of less than 20%. Our results are consistent through
two different normalization methods and two different statistical
analysis procedures.CONCLUSION:Our findings demonstrate that the
entire plant genome undergoes transcriptional modulation in response
to infection and genetic variation. The pervasive low-magnitude remodeling
of the transcriptome may be an integral component of physiological
adaptation in soybean, and in all eukaryotes.},
doi = {10.1186/1471-2164-10-49},
issn = {1471-2164},
pubmedid = {19171053},
url = {http://www.biomedcentral.com/1471-2164/10/49}
}
@ARTICLE{Zhou2006a,
author = {Zhou, Longhu and Thakur, Chandar S. and Molinaro, Ross J. and Paranjape,
Jayashree M. and Hoppes, Rieuwert and Jeang, Kuan-Teh and Silverman,
Robert H. and Torrence, Paul F.},
title = {Delivery of 2-5A cargo into living cells using the Tat cell penetrating
peptide: 2-5A-tat},
journal = {Bioorganic \& Medicinal Chemistry},
year = {2006},
volume = {14},
pages = {7862--7874},
number = {23},
month = dec,
abstract = {2',5'-Oligoadenylate tetramer (2-5A) has been chemically conjugated
to short HIV-1 Tat peptides to provide 2-5A-tat chimeras. Two different
convergent synthetic approaches have been employed to provide such
2-5A-tat bioconjugates. One involved generation of a bioconjugate
through reaction of a cysteine terminated Tat peptide with a [alpha]-chloroacetyl
derivative of 2-5A. The second synthetic strategy was based upon
a cycloaddition reaction of an azide derivative of 2-5A with a Tat
peptide bearing an alkyne function. Either bioconjugate of 2-5A-tat
was able to activate human RNase L. The union of 2-5A and Tat peptide
provided an RNase L-active chimeric nucleopeptide with the ability
to be taken up by cells by virtue of the Tat peptide and to activate
RNase L in intact cells. This strategy provides a valuable vehicle
for the entry of the charged 2-5A molecule into cells and may provide
a means for targeted destruction of HIV RNA in vivo.},
issn = {0968-0896},
keywords = {Ribonuclease L, Interferon, Cycloaddition, Sulfhydryl alkylation,
RNA, 2',5'-Oligoadenylate},
url = {http://www.sciencedirect.com/science/article/B6TF8-4M5F0Y1-6/2/fac000fa65675ad32e54e6fc2a671d68}
}
@ARTICLE{Zhou2008a,
author = {Zhou, Li and Wang, Hongjie and Zhong, Xing and Jin, Yulan and Mi,
Qing-Sheng and Sharma, Ashok and McIndoe, Richard and Garge, Nikhil
and Podolsky, Robert and She, Jin-Xiong},
title = {The IL-10 and IFN-? pathways are essential to the potent immunosuppressive
activity of cultured CD8+ NKT-like cells},
journal = {Genome Biology},
year = {2008},
volume = {9},
pages = {R119},
number = {7},
abstract = {BACKGROUND:CD8+ NKT-like cells are naturally occurring but rare T
cells that express both T cell and natural killer cell markers. These
cells may play key roles in establishing tolerance to self-antigens;
however, their mechanism of action and molecular profiles are poorly
characterized due to their low frequencies. We developed an efficient
in vitro protocol to produce CD8+ T cells that express natural killer
cell markers (CD8+ NKT-like cells) and extensively characterized
their functional and molecular phenotypes using a variety of techniques.RESULTS:Large
numbers of CD8+ NKT-like cells were obtained through culture of naïve
CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose
IL-2. These cells possess potent activity in suppressing the proliferation
of naïve responder T cells. Gene expression profiling suggests that
the cultured CD8+ NKT-like cells and the naïve CD8+ T cells differ
by more than 2-fold for about 3,000 genes, among which 314 are upregulated
by more than 5-fold and 113 are upregulated by more than 10-fold
in the CD8+ NKT-like cells. A large proportion of the highly upregulated
genes are soluble factors or surface markers that have previously
been implicated in immune suppression or are likely to possess immunosuppressive
properties. Many of these genes are regulated by two key cytokines,
IL-10 and IFN-?. The immunosuppressive activities of cells cultured
from IL-10-/- and IFN-?-/- mice are reduced by about 70% and about
50%, respectively, compared to wild-type mice.CONCLUSION:Immunosuppressive
CD8+ NKT-like cells can be efficiently produced and their immunosuppressive
activity is related to many surface and soluble molecules regulated
by IL-10 and IFN-?.},
doi = {10.1186/gb-2008-9-7-r119},
issn = {1465-6906},
pubmedid = {18664279},
url = {http://genomebiology.com/2008/9/7/R119}
}
@ARTICLE{Zhou2006b,
author = {Zhou, Mingyuan and Li, Xin-min and Lavker, Robert M.},
title = {Transcriptional Profiling of Enriched Populations of Stem Cells Versus
Transient Amplifying Cells: A COMPARISON OF LIMBAL AND CORNEAL EPITHELIAL
BASAL CELLS},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {19600--19609},
number = {28},
month = jul,
abstract = {The basal layer of limbal and central corneal epithelium is enriched
in stem cells and transient amplifying cells, respectively. This
physical separation of stem and transient amplifying cells makes
the limbal/corneal epithelium an exceptionally suitable system for
isolating basal cells enriched in these two proliferative populations.
Prior attempts to isolate epithelial stem cells used methods such
as proteolytic tissue dissociation and cell sorting that could potentially
alter their gene expression profile. Using laser capture microdissection,
we were able to isolate resting limbal and corneal basal cells from
frozen sections with minimal tissue processing, thereby improving
the yield and quality of RNA. Analyses of RNA isolated from 300 limbal
and corneal basal cells from eight mice revealed a set of [~]100
genes that are differentially expressed in limbal cells versus corneal
epithelial basal cells. Semiquantitative reverse transcription-PCR
confirmed the up-regulation of three limbal and three corneal genes.
LacZ identification of epiregulin from epiregulin-null mice and immunohistochemical
staining of wild type mice confirmed that epiregulin, one of the
limbal epithelium-enriched genes, was associated with the limbal
epithelial basal cells. Within the limbal and corneal basal cells,
we detected previously unknown genes that were differentially expressed
in these two regions that contribute further to our understanding
of the unique heterogeneity of these two closely related basal cell
populations. Our findings indicate that we can obtain accurate gene
expression profiles of the stem cell-enriched limbal basal cell population
in their "natural" quiescent state.},
url = {http://www.jbc.org/cgi/content/abstract/281/28/19600}
}
@ARTICLE{Zhou2007,
author = {Zhou, Qingde and Amar, Salomon},
title = {Identification of Signaling Pathways in Macrophage Exposed to Porphyromonas
gingivalis or to Its Purified Cell Wall Components},
journal = {J. Immunol.},
year = {2007},
volume = {179},
pages = {7777--7790},
number = {11},
month = dec,
abstract = {Porphyromonas gingivalis (P. gingivalis) can trigger an inflammatory
condition leading to the destruction of periodontal tissues. However
P. gingivalis LPS and its fimbriae (FimA) play different roles compared
with the live bacteria in the context of intracellular molecule induction
and cytokine secretion. To elucidate whether this difference results
from different signaling pathways in host immune response to P. gingivalis,
its LPS, or its FimA, we examined gene expression profile of human
macrophages exposed to P. gingivalis, its LPS, or its FimA. A comparison
of gene expression resulted in the identification of three distinct
groups of expressed genes. Furthermore, computer-assisted promoter
analysis of a subset of each group of differentially regulated genes
revealed four putative transcriptional regulation models that associate
with transcription factors NF{kappa}B, IRF7, and KLF4. Using gene
knockout mice and siRNA to silence mouse genes, we showed that both
TLR2 and TLR7 are essential for the induction of NF{kappa}B-containing
genes and NF{kappa}B-IFN-sensitive response element (ISRE) cocontaining
genes by either P. gingivalis or its purified components. The gene
induction via either TLR2 or TLR7 is dependent on both MyD88 and
p38 MAPK. However, the unique induction of IFN-{beta} by P. gingivalis
LPS requires TLR7 and IFN{alpha}{beta}R cosignaling, and the induction
of ISRE-containing gene is dependent on the activation of IFN-{beta}
autocrine loop. Taken together, these data demonstrate that P. gingivalis
and its components induce NF{kappa}B-containing genes through either
TLR2- or TLR7-MyD88-p38 MAPK pathway, while P. gingivalis LPS uniquely
induces ISRE-containing genes, which requires IFN{alpha}{beta}R signaling
involving IRF7, KLF4, and pY701 STAT1.},
url = {http://www.jimmunol.org/cgi/content/abstract/179/11/7777}
}
@ARTICLE{Zhou2005,
author = {Zhou, Qing and Shima, James E. and Nie, Rong and Friel, Patrick J.
and Griswold, Michael D.},
title = {Androgen-Regulated Transcripts in the Neonatal Mouse Testis as Determined
Through Microarray Analysis},
journal = {Biol Reprod},
year = {2005},
volume = {72},
pages = {1010--1019},
number = {4},
month = apr,
abstract = {Androgens are required for normal spermatogenesis in mammalian testes.
These hormones directly regulate testicular somatic cells that, in
turn, support germ cell differentiation. However, the identity of
genes under androgen regulation in the testis are not well known.
In the present study, neonatal male mice (8 days postpartum) treated
by testosterone propionate (TP) were used to study androgen action
in the testis as evidenced by alterations in gene expression. Mice
were treated with 0.5 mg of TP or dihydrotestosterone (DHT) or vehicle
(oil), and testes were harvested 4, 8, and 16 h after treatment.
Global gene expression was monitored by microarray analysis. Real-time
reverse transcription-polymerase chain reaction was performed to
confirm the microarray results. The methodology was verified by confirming
the presence of previously characterized TP-regulated genes, including
Pem in Sertoli cells and Cyp17a1 in Leydig cells. No significant
differences in gene expression were found between TP- and DHT-treated
samples. Microarray analysis identified 141, 119, and 109 up-regulated
genes at 4, 8 and 16 h after TP treatment, respectively, and 83,
99, and 111 down-regulated genes at the same corresponding time points.
The androgen regulation of the selected gene was verified further
using testes from flutamide-treated adult mice and isolated Sertoli
cells in culture. The data generated in the present study may serve
as a foundation for hypothesis-driven research and provide insights
regarding gene networks and pathways under androgen control in the
testis.},
url = {http://www.biolreprod.org/cgi/content/abstract/72/4/1010}
}
@ARTICLE{Zhou2009a,
author = {Zhou, Quan-Yong and Fang, Ming-Di and Huang, Ting-Hua and Li, Chang-Chun
and Yu, Mei and Zhao, Shu-Hong},
title = {Detection of differentially expressed genes between Erhualian and
Large White placentas on day 75 and 90 of gestation},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {337},
number = {1},
abstract = {BACKGROUND:Placental efficiency is strongly associated with litter
size, fetal weight and prenatal mortality. Together with its rapid
growth during late gestation, the Large White pig breed shows a significant
increase in placental size and weight, but this does not occur in
the highly prolific Chinese pig breeds. To understand the molecular
basis of placental development during late gestation in Chinese indigenous
and Western breeds with different placental efficiency, female placental
samples were collected from six pregnant Erhualian gilts at gestation
day 75 (E75) and day 90 (E90) and from six pregnant Large White gilts
at gestation day 75 (L75) and day 90 (L90). Two female placentas
from one sow were used to extract RNA and then pooled in equal volumes.
Twelve pooled samples were hybridized to the porcine Affymetrix GeneChip.RESULTS:A
total of 226 and 577 transcripts were detected that were differentially
expressed between E75 and L75 and between E90 and L90 (p < 0.01,
q < 0.2), respectively. Gene Ontology (GO) analysis revealed that
these genes belong to the class of genes that participate in angiogenesis
and development. Real-time RT-PCR confirmed the differential expression
of eight selected genes. Significant differential expression of five
genes in the VEGF pathway was also detected between the breeds. A
search of chromosomal location revealed that 44 differentially expressed
genes located to QTL regions related to reproduction. Differential
expression of six candidate imprinted genes was also confirmed. Three
of the six genes (PLAGL1, DIRAS3, and SLC38A4) showed monoallelic
expression in the porcine placenta.CONCLUSION:Our study detected
many genes that showed differential expression between placentas
of two divergent breed of pigs, and confirmed the imprinting of three
genes. These findings help to elucidate the genetic control of placental
efficiency and improve the understanding of placental development.},
doi = {10.1186/1471-2164-10-337},
issn = {1471-2164},
pubmedid = {19630995},
url = {http://www.biomedcentral.com/1471-2164/10/337}
}
@ARTICLE{Zhou2007a,
author = {Zhou, Tong and Chou, Jeff and Zhou, Yingchun and Simpson, Dennis
A. and Cao, Feng and Bushel, Pierre R. and Paules, Richard S. and
Kaufmann, William K.},
title = {Ataxia Telangiectasia-Mutated Dependent DNA Damage Checkpoint Functions
Regulate Gene Expression in Human Fibroblasts},
journal = {Mol. Cancer Res.},
year = {2007},
volume = {5},
pages = {813--822},
number = {8},
month = aug,
abstract = {The relationships between profiles of global gene expression and DNA
damage checkpoint functions were studied in cells from patients with
ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast
lines displayed the expected hypersensitivity to ionizing radiation
(IR) and defects in DNA damage checkpoints. Profiles of global gene
expression in AT cells were determined at 2, 6, and 24 h after treatment
with 1.5-Gy IR or sham treatment and were compared with those previously
recognized in normal human fibroblasts. Under basal conditions, 160
genes or expressed sequence tags were differentially expressed in
AT and normal fibroblasts, and these were associated by gene ontology
with insulin-like growth factor binding and regulation of cell growth.
On DNA damage, 1,091 gene mRNAs were changed in at least two of the
three AT cell lines. When compared with the 1,811 genes changed in
normal human fibroblasts after the same treatment, 715 were found
in both AT and normal fibroblasts, including most genes categorized
by gene ontology into cell cycle, cell growth, and DNA damage response
pathways. However, the IR-induced changes in these 715 genes in AT
cells usually were delayed or attenuated in comparison with normal
cells. The reduced change in DNA damage response genes and the attenuated
repression of cell cycle-regulated genes may account for the defects
in cell cycle checkpoint function in AT cells. (Mol Cancer Res 2007;5(8):813-22)},
url = {http://mcr.aacrjournals.org/cgi/content/abstract/5/8/813}
}
@ARTICLE{Zhou2010a,
author = {Zhou, Tian and Wang, Shanshan and Ren, Haigang and Qi, Xin-Rui and
Luchetti, Sabina and Kamphuis, Willem and Zhou, Jiang-Ning and Wang,
Guanghui and Swaab, Dick F.},
title = {Dendritic cell nuclear protein-1, a novel depression-related protein,
upregulates corticotropin-releasing hormone expression},
journal = {Brain},
year = {2010},
volume = {133},
pages = {3069--3079},
number = {10},
month = oct,
abstract = {The recently discovered dendritic cell nuclear protein-1 is the product
of a novel candidate gene for major depression. The A allele encodes
full-length dendritic cell nuclear protein-1, while the T allele
encodes a premature termination of translation at codon number 117
on chromosome 5. In the present study we investigate whether the
two forms of dendritic cell nuclear protein-1 might act on corticotropin-releasing
hormone, which plays a crucial role in the stress response and in
the pathogenesis of depression. The messenger RNA expression of dendritic
cell nuclear protein-1 appeared to be increased in the laser micro-dissected
paraventricular nucleus of patients with depression compared with
control subjects. Dendritic cell nuclear protein-1 was also found
to be co-localized with corticotropin-releasing hormone in paraventricular
nucleus neurons. Moreover, full-length dendritic cell nucleus protein-1
bound to and transactivated the promoter of corticotropin-releasing
hormone in human embryonic kidney 293 cells. We propose that full-length
dendritic cell nucleus protein-1 may play a role in the pathogenesis
of depressive disorders by enhancing corticotropin-releasing hormone
expression in the hypothalamic paraventricular nucleus.},
url = {http://brain.oxfordjournals.org/cgi/content/abstract/133/10/3069}
}
@ARTICLE{Zhou2009b,
author = {Zhou, Weiyin and Calciano, Margaret and Jordan, Heather and Brenner,
Michael and Johnson, Seth and Wu, Darong and Lei, Lin and Pallares,
Diego and Beurdeley, Pascale and Rouet, Fabien and Gill, Pritmohinder
and Bracco, Laurent and Soucaille, Cyril and Einstein, Richard},
title = {High resolution analysis of the human transcriptome: detection of
extensive alternative splicing independent of transcriptional activity},
journal = {BMC Genetics},
year = {2009},
volume = {10},
pages = {63},
number = {1},
abstract = {BACKGROUND:Commercially available microarrays have been used in many
settings to generate expression profiles for a variety of applications,
including target selection for disease detection, classification,
profiling for pharmacogenomic response to therapeutics, and potential
disease staging. However, many commercially available microarray
platforms fail to capture transcript diversity produced by alternative
splicing, a major mechanism for driving proteomic diversity through
transcript heterogeneity.RESULTS:The human Genome-Wide SpliceArray™
(GWSA), a novel microarray platform, utilizes an existing probe design
concept to monitor such transcript diversity on a genome scale. The
human GWSA allows the detection of alternatively spliced events within
the human genome through the use of exon body and exon junction probes
to provide a direct measure of each transcript, through simple calculations
derived from expression data. This report focuses on the performance
and validation of the array when measured against standards recently
published by the Microarray Quality Control (MAQC) Project. The array
was shown to be highly quantitative, and displayed greater than 85%
correlation with the HG-U133 Plus 2.0 array at the gene level while
providing more extensive coverage of each gene. Almost 60% of splice
events among genes demonstrating differential expression of greater
than 3 fold also contained extensive splicing alterations. Importantly,
almost 10% of splice events within the gene set displaying constant
overall expression values had evidence of transcript diversity. Two
examples illustrate the types of events identified: LIM domain 7
showed no differential expression at the gene level, but demonstrated
deregulation of an exon skip event, while erythrocyte membrane protein
band 4.1 -like 3 was differentially expressed and also displayed
deregulation of a skipped exon isoform.CONCLUSION:Significant changes
were detected independent of transcriptional activity, indicating
that the controls for transcript generation and transcription are
distinct, and require novel tools in order to detect changes in specific
transcript quantity. Our results demonstrate that the SpliceArray™
design will provide researchers with a robust platform to detect
and quantify specific changes not only in overall gene expression,
but also at the individual transcript level.},
doi = {10.1186/1471-2156-10-63},
issn = {1471-2156},
pubmedid = {19804644},
url = {http://www.biomedcentral.com/1471-2156/10/63}
}
@ARTICLE{Zhou2008b,
author = {Zhou, Yinli and Capuco, Anthony V. and Jiang, Honglin},
title = {Involvement of connective tissue growth factor (CTGF) in insulin-like
growth factor-I (IGF1) stimulation of proliferation of a bovine mammary
epithelial cell line},
journal = {Domestic Animal Endocrinology},
year = {2008},
volume = {35},
pages = {180--189},
number = {2},
month = aug,
abstract = {The objective of this study was to determine the mechanism by which
insulin-like growth factor-I (IGF1) stimulates proliferation of mammary
epithelial cells, using the bovine mammary epithelial cell line MAC-T
as a model. IGF1 significantly up- or down-regulated the expression
of 155 genes in MAC-T cells. Among the most significantly suppressed
was the gene for connective tissue growth factor (CTGF), a secretory
protein that has both proliferative and apoptotic effects and is
also a low-affinity binding protein of IGF1. IGF1 inhibited CTGF
expression through the PI3K-Akt signaling pathway. Administration
of growth hormone (GH), a strong stimulator of IGF1 production in
vivo, decreased mammary CTGF mRNA in cattle; however, GH did not
affect CTGF expression in MAC-T cells, suggesting that IGF1 may also
inhibit CTGF expression in the mammary gland. Added alone CTGF stimulated
proliferation of MAC-T cells, but in combination with IGF1 it attenuated
IGF1's stimulation of proliferation of MAC-T cells. Excess IGF1 reversed
this attenuating effect of CTGF. Despite being an IGF binding protein,
CTGF did not affect IGF1-induced phosphorylation of IGF1 receptor
(IGF1R) or IGF1R expression in MAC-T cells, indicating that the attenuating
effect of CTGF on IGF1 stimulated proliferation of MAC-T cells was
not mediated by decreasing IGF1's ability to bind to IGF1R or by
decreasing IGF1R expression. Overall, these results suggest a novel
biochemical and functional relationship between CTGF and IGF1 in
the bovine mammary gland, where IGF1 may inhibit CTGF expression
to reduce the attenuating effect of CTGF on IGF1 stimulated proliferation
of epithelial cells.},
issn = {0739-7240},
keywords = {IGF1, Cell proliferation, Mammary, Bovine, CTGF},
url = {http://www.sciencedirect.com/science/article/B6T62-4ST4N2H-1/2/921b022facac2841871fb8897b1f3892}
}
@ARTICLE{Zhou2011,
author = {Zhou, Yanhong and Michelhaugh, Sharon K. and Schmidt, Carl J. and
Liu, Jun S. and Bannon, Michael J. and Lin, Zhicheng},
title = {Ventral midbrain correlation between genetic variation and expression
of the dopamine transporter gene in cocaine-abusing versus non-abusing
subjects},
journal = {Addiction Biology},
year = {2011},
pages = {no--no},
abstract = {Altered activity of the human dopamine transporter gene (hDAT) is
associated with several common and severe brain disorders, including
cocaine abuse. However, there is little a priori information on whether
such alterations are due to nature (genetic variation) or nurture
(human behaviors such as cocaine abuse). This study investigated
the correlation between seven markers throughout hDAT and its mRNA
levels in postmortem ventral midbrain tissues from 18 cocaine abusers
and 18 strictly matched drug-free controls in the African-American
population. Here, we show that one major haplotype with the same
frequency in cocaine abusers versus drug-free controls displays a
37.1% reduction of expression levels in cocaine abusers compared
with matched controls (PÂ =Â 0.0057). The most studied genetic marker,
variable number tandem repeats (VNTR) located in Exon 15 (3′VNTR),
is not correlated with hDAT mRNA levels. A 5′ upstream VNTR (rs70957367)
has repeat numbers that are positively correlated with expression
levels in controls (r2Â =Â 0.9536, PÂ =Â 0.0235), but this positive
correlation disappears in cocaine abusers. The findings suggest that
varying hDAT activity is attributable to both genetics and cocaine
abuse.},
doi = {10.1111/j.1369-1600.2011.00391.x},
issn = {1369-1600},
keywords = {Addiction, DAT, epigenetics, expressional variation, pharmacogenomics,
postmortem},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1369-1600.2011.00391.x}
}
@ARTICLE{Zhou2008c,
author = {Zhou, Yuzhao and Vaidya, Vishal S. and Brown, Ronald P. and Zhang,
Jun and Rosenzweig, Barry A. and Thompson, Karol L. and Miller, Terry
J. and Bonventre, Joseph V. and Goering, Peter L.},
title = {Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers
in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury,
and Chromium},
journal = {Toxicol. Sci.},
year = {2008},
volume = {101},
pages = {159--170},
number = {1},
month = jan,
abstract = {Sensitive biomarkers are needed to detect kidney injury at the earliest
stages. The objective of this study was to determine whether the
appearance of kidney injury molecule-1 (Kim-1) protein ectodomain
in urine and kidney injury molecule-1/hepatitis A viral cellular
receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be
more predictive of renal injury after exposure to nephrotoxicants
when compared to traditionally used biomarkers. Male Sprague-Dawley
rats were injected with a range of doses of gentamicin, mercury (Hg;
HgCl2), or chromium (Cr; K2Cr2O7). The results showed that increases
in urinary Kim-1 and kidney Kim-1/Havcr1 gene expression paralleled
the degree of severity of renal histopathology and were detected
at lower doses of nephrotoxicants when compared to blood urea nitrogen
(BUN), serum creatinine, and urinary N-acetyl-{beta}-D-glucosaminidase
(NAG). In a time course study, urinary Kim-1 was elevated within
24 h after exposure to gentamicin (100 mg/kg), Hg (0.25 mg/kg), or
Cr (5 mg/kg) and remained elevated through 72 h. NAG responses were
nephrotoxicant dependent with elevations occurring early (gentamicin),
late (Cr), or no change (Hg). At 72 h, after treatment with any of
the three nephrotoxicants, there was increased Kim-1 immunoreactivity
and necrosis involving [~]50% of the proximal tubules; however, only
urinary Kim-1 was significantly increased, while BUN, serum creatinine,
and NAG were not different from controls. In rats treated with the
hepatotoxicant galactosamine (1.1 mg/kg), serum alanine aminotransferase
was increased, but no increase in urinary Kim-1 was observed. Urinary
Kim-1 and kidney Kim-1/Havcr1 expression appear to be sensitive and
tissue-specific biomarkers that will improve detection of early acute
kidney injury following exposure to nephrotoxic chemicals and drugs.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/101/1/159}
}
@ARTICLE{Zhou2010,
author = {Zhou, Yong-Li and Xu, Mei-Rong and Zhao, Ming-Fu and Xie, Xue-Wen
and Zhu, Ling-Hua and Fu, Bin-Ying and Li, Zhi-Kang},
title = {Genome-wide gene responses in a transgenic rice line carrying the
maize resistance gene Rxo1 to the rice bacterial streak pathogen,
Xanthomonas oryzae pv. oryzicola},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {78},
number = {1},
abstract = {BACKGROUND:Non-host resistance in rice to its bacterial pathogen,
Xanthomonas oryzae pv. oryzicola (Xoc), mediated by a maize NBS-LRR
type R gene, Rxo1 shows a typical hypersensitive reaction (HR) phenotype,
but the molecular mechanism(s) underlying this type of non-host resistance
remain largely unknown.RESULTS:A microarray experiment was performed
to reveal the molecular mechanisms underlying HR of rice to Xoc mediated
by Rxo1 using a pair of transgenic and non-transgenic rice lines.
Our results indicated that Rxo1 appeared to function in the very
early step of the interaction between rice and Xoc, and could specifically
activate large numbers of genes involved in signaling pathways leading
to HR and some basal defensive pathways such as SA and ET pathways.
In the former case, Rxo1 appeared to differ from the typical host
R genes in that it could lead to HR without activating NDR1. In the
latter cases, Rxo1 was able to induce a unique group of WRKY TF genes
and a large set of genes encoding PPR and RRM proteins that share
the same G-box in their promoter regions with possible functions
in post-transcriptional regulation.CONCLUSIONS:In conclusion, Rxo1,
like most host R genes, was able to trigger HR against Xoc in the
heterologous rice plants by activating multiple defensive pathways
related to HR, providing useful information on the evolution of plant
resistance genes. Maize non-host resistance gene Rxo1 could trigger
the pathogen-specific HR in heterologous rice, and ultimately leading
to a localized programmed cell death which exhibits the characteristics
consistent with those mediated by host resistance genes, but a number
of genes encoding pentatricopeptide repeat and RNA recognition motif
protein were found specifically up-regulated in the Rxo1 mediated
disease resistance. These results add to our understanding the evolution
of plant resistance genes.},
doi = {10.1186/1471-2164-11-78},
issn = {1471-2164},
pubmedid = {20122142},
url = {http://www.biomedcentral.com/1471-2164/11/78}
}
@ARTICLE{Zhu2005,
author = {Zhu, Bingmei and Ping, Guichen and Shinohara, Yasuo and Zhang, Yong
and Baba, Yoshinobu},
title = {Comparison of gene expression measurements from cDNA and 60-mer oligonucleotide
microarrays},
journal = {Genomics},
year = {2005},
volume = {85},
pages = {657--665},
number = {6},
month = jun,
abstract = {As the data generated by microarray technology continue to amass,
it is necessary to compare and combine gene expression data from
different platforms. To evaluate the performance of cDNA and long
oligonucleotide (60-mer) arrays, we generated gene expression profiles
for two cancer cell lines and compared the data between the two platforms.
All 6182 unique genes represented on both platforms were included
in the analysis. A limited correlation (r = 0.4708) was obtained
and the difference in measurement of low-expression genes was considered
to contribute to the limited correlation. Further restriction of
the data set to differentially expressed genes detected in cDNA microarrays
(1205 genes) and oligonucleotide arrays (1325 genes) showed modest
correlations of 0.7076 and 0.6441 between the two platforms. Quantitative
real-time PCR measurements of a set of 10 genes showed better correlation
with oligonucleotide arrays. Our results demonstrate that there is
substantial variation in the data generated from cDNA and 60-mer
oligonucleotide arrays. Although general agreement was observed in
measurements of differentially expressed genes, we suggest that data
from different platforms could not be directly amassed.},
issn = {0888-7543},
keywords = {cDNA microarray, 60-mer oligonucleotide microarray, Gene expression
profile, Quantitative real-time PCR},
url = {http://www.sciencedirect.com/science/article/B6WG1-4FRJKWK-3/2/8e14993586ab3f62552a1bec7d89b40e}
}
@ARTICLE{Zhu2006,
author = {Zhu, Bingmei and Xu, Feng and Baba, Yoshinobu},
title = {An evaluation of linear RNA amplification in cDNA microarray gene
expression analysis},
journal = {Molecular Genetics and Metabolism},
year = {2006},
volume = {87},
pages = {71--79},
number = {1},
month = jan,
abstract = {DNA microarray is becoming a common tool across a broad range of disciplines,
particularly in the basic and clinical biomedical sciences. However,
the limitation of this technology is the requirement for relatively
large amount of RNA for labeling and hybridization. T7-based linear
amplification technique can overcome this limitation and enables
consumption of very low amount of samples. In this study, we utilized
a low RNA input fluorescent linear amplification kit from Agilent
to amplify 0.2 [mu]g total RNA and compared the gene expression profiles
generated from amplified aRNA and total RNA. Our results demonstrated
that nanograms total RNA can be amplified reproducibly with this
protocol and can generate gene expression profiles comparable with
unamplified total RNA. Furthermore, quantitative real-time PCR measurements
of a set of 10 genes showed good correlation with amplified aRNA
arrays.},
issn = {1096-7192},
keywords = {cDNA microarray, Linear RNA amplification, Gene expression profile,
Quantitative real-time PCR},
url = {http://www.sciencedirect.com/science/article/B6WNG-4H8MP6J-1/2/e3c56860b48266a2c1a59e1e50fc1a22}
}
@ARTICLE{Zhu2008,
author = {Zhu, Bing-Mei and McLaughlin, Sara K. and Na, Risu and Liu, Jie and
Cui, Yongzhi and Martin, Cyril and Kimura, Akiko and Robinson, Gertraud
W. and Andrews, Nancy C. and Hennighausen, Lothar},
title = {Hematopoietic-specific Stat5-null mice display microcytic hypochromic
anemia associated with reduced transferrin receptor gene expression},
journal = {Blood},
year = {2008},
volume = {112},
pages = {2071--2080},
number = {5},
month = sep,
abstract = {Iron is essential for all cells but is toxic in excess, so iron absorption
and distribution are tightly regulated. Serum iron is bound to transferrin
and enters erythroid cells primarily via receptor-mediated endocytosis
of the transferrin receptor (Tfr1). Tfr1 is essential for developing
erythrocytes and reduced Tfr1 expression is associated with anemia.
The transcription factors STAT5A/B are activated by many cytokines,
including erythropoietin. Stat5a/b-/- mice are severely anemic and
die perinatally, but no link has been made to iron homeostasis. To
study the function of STAT5A/B in vivo, we deleted the floxed Stat5a/b
locus in hematopoietic cells with a Tie2-Cre transgene. These mice
exhibited microcytic, hypochromic anemia, as did lethally irradiated
mice that received a transplant of Stat5a/b-/- fetal liver cells.
Flow cytometry and RNA analyses of erythroid cells from mutant mice
revealed a 50% reduction in Tfr1 mRNA and protein. We detected STAT5A/B
binding sites in the first intron of the Tfr1 gene and found that
expression of constitutively active STAT5A in an erythroid cell line
increased Tfr1 levels. Chromatin immunoprecipitation experiments
confirmed the binding of STAT5A/B to these sites. We conclude that
STAT5A/B is an important regulator of iron update in erythroid progenitor
cells via its control of Tfr1 transcription.},
url = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/5/2071}
}
@ARTICLE{Zhu2010,
author = {Zhu, Chang-Qi and Ding, Keyue and Strumpf, Dan and Weir, Barbara
A. and Meyerson, Matthew and Pennell, Nathan and Thomas, Roman K.
and Naoki, Katsuhiko and Ladd-Acosta, Christine and Liu, Ni and Pintilie,
Melania and Der, Sandy and Seymour, Lesley and Jurisica, Igor and
Shepherd, Frances A. and Tsao, Ming-Sound},
title = {Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy
in Resected Non-Small-Cell Lung Cancer},
journal = {J. Clin. Oncol.},
year = {2010},
volume = {28},
pages = {4417--4424},
number = {29},
month = oct,
abstract = {PurposeThe JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine
(ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized
that expression profiling may identify stage-independent subgroups
who might benefit from ACT. Patients and MethodsGene expression profiling
was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation
[OBS], 71 ACT). The minimum gene set that was selected for the greatest
separation of good and poor prognosis patient subgroups in OBS patients
was identified. The prognostic value of this gene signature was tested
in four independent published microarray data sets and by quantitative
reverse-transcriptase polymerase chain reaction (RT-qPCR). ResultsA
15-gene signature separated OBS patients into high-risk and low-risk
subgroups with significantly different survival (hazard ratio [HR],
15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001;
stage II HR, 13.47; P < .001). The prognostic effect was verified
in the same 62 OBS patients where gene expression was assessed by
qPCR. Furthermore, it was validated consistently in four separate
microarray data sets (total 356 stage IB to II patients without adjuvant
treatment) and additional JBR.10 OBS patients by qPCR (n = 19). The
signature was also predictive of improved survival after ACT in JBR.10
high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but
not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133;
interaction P < .001). Significant interaction between risk groups
and ACT was verified by qPCR. ConclusionThis 15-gene expression signature
is an independent prognostic marker in early-stage, completely resected
NSCLC, and to our knowledge, is the first signature that has demonstrated
the potential to select patients with stage IB to II NSCLC most likely
to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.},
url = {http://jco.ascopubs.org/cgi/content/abstract/28/29/4417}
}
@ARTICLE{Zhu2011,
author = {Zhu, Hong and Dardick, Chris and Beers, Eric and Callanhan, Ann and
Xia, Rui and Yuan, Rongcai},
title = {Transcriptomics of shading-induced and NAA-induced abscission in
apple (Malus domestica) reveals a shared pathway involving reduced
photosynthesis, alterations in carbohydrate transport and signaling
and hormone crosstalk},
journal = {BMC Plant Biology},
year = {2011},
volume = {11},
pages = {138},
number = {1},
abstract = {BACKGROUND:Naphthaleneacetic acid (NAA), a synthetic auxin analogue,
is widely used as an effective thinner in apple orchards. When applied
shortly after fruit set, some fruit abscise leading to improved fruit
size and quality. However, the thinning results of NAA are inconsistent
and difficult to predict, sometimes leading to excess fruit drop
or insufficient thinning which are costly to growers. This unpredictability
reflects our incomplete understanding of the mode of action of NAA
in promoting fruit abscission.RESULTS:Here we compared NAA-induced
fruit drop with that caused by shading via gene expression profiling
performed on the fruit abscission zone (FAZ), sampled 1, 3, and 5
d after treatment. More than 700 genes with significant changes in
transcript abundance were identified from NAA-treated FAZ. Combining
results from both treatments, we found that genes associated with
photosynthesis, cell cycle and membrane/cellular trafficking were
downregulated. On the other hand, there was up-regulation of genes
related to ABA, ethylene biosynthesis and signaling, cell wall degradation
and programmed cell death. While the differentially expressed gene
sets for NAA and shading treatments shared only 25% identity, NAA
and shading showed substantial similarity with respect to the classes
of genes identified. Specifically, photosynthesis, carbon utilization,
ABA and ethylene pathways were affected in both NAA- and shading-induced
young fruit abscission. Moreover, we found that NAA, similar to shading,
directly interfered with leaf photosynthesis by repressing photosystem
II (PSII) efficiency within 10 minutes of treatment, suggesting that
NAA and shading induced some of the same early responses due to reduced
photosynthesis, which concurred with changes in hormone signaling
pathways and triggered fruit abscission.CONCLUSIONS:This study provides
an extensive transcriptome study and a good platform for further
investigation of possible regulatory genes involved in the induction
of young fruit abscission in apple, which will enable us to better
understand the mechanism of fruit thinning and facilitate the selection
of potential chemicals for the thinning programs in apple.},
doi = {10.1186/1471-2229-11-138},
issn = {1471-2229},
pubmedid = {22003957},
url = {http://www.biomedcentral.com/1471-2229/11/138}
}
@ARTICLE{Zhu2010a,
author = {Zhu, Jinsong and Busche, Jefferson M. and Zhang, Xing},
title = {Identification of juvenile hormone target genes in the adult female
mosquitoes},
journal = {Insect Biochemistry and Molecular Biology},
year = {2010},
volume = {40},
pages = {23--29},
number = {1},
month = jan,
abstract = {Many aspects of reproductive maturation in newly emerged adult female
mosquitoes are controlled by juvenile hormone (JH). However, the
molecular basis of this hormonal regulation remains poorly understood.
In this study, we analyzed transcriptome changes in young female
adults after topical application of exogenous JH. mRNA levels of
16 and 72 genes were enhanced at 3 h and 12 h after hormone administration,
respectively. The observed upregulations can be also induced by the
JH analogues, methoprene and pyriproxyfen, but not by farnesol, indicating
that these responses are JH-specific. Among the genes activated by
JH is the mosquito Krüppel homolog 1 (Kr-h1) gene. Studies in the
beetle Tribolium castaneum have indicated that Kr-h1 is transcriptionally
activated by JH during metamorphosis and encodes a gene expression
regulator acting downstream of the methoprene-tolerant (Met) gene
in the JH signaling pathway. We found that the upregulation of AaKr-h1
after eclosion relied on the function of the mosquito Met protein,
suggesting that a conserved JH signaling pathway is utilized both
in the metamorphosis of T. castaneum and in the adult reproductive
maturation of the Aedes aegypti mosquito. This study lays a foundation
for a better understanding of the mechanisms of juvenile hormone
action.},
issn = {0965-1748},
keywords = {Mosquito, Juvenile hormone, Microarray, Krüppel homolog 1, Methoprene-tolerant},
url = {http://www.sciencedirect.com/science/article/B6T79-4XY4MYN-2/2/31e7c0cc020bb73e6abd68c9e8aaad0d}
}
@ARTICLE{Zhu2009,
author = {Zhu, Jin and Patzoldt, William L. and Radwan, Osman and Tranel, Patrick
J. and Clough, Steven J.},
title = {Effects of Photosystem-II-Interfering Herbicides Atrazine and Bentazon
on the Soybean Transcriptome},
journal = {The Plant Genome},
year = {2009},
volume = {2},
pages = {191--205},
number = {2},
month = jul,
abstract = {Atrazine and bentazon are both photosystem-II (PSII)-inhibiting herbicides
that interfere with photosynthetic electron transport, provoking
oxidative stress. While atrazine is lethal to soybean [Glycine max
(L.) Merr.], bentazon does not kill soybean because of the capability
of soybeans to metabolize the herbicide. Gene expression profiling
was conducted using cDNA microarrays to understand the responses
of soybeans to PSII interruption and concomitant stress caused by
atrazine and bentazon by monitoring expression at 1, 2, 4, and 8
h after treatment (HAT). The microarray study revealed that 6646
genes were differentially expressed with high statistical significance
over the experiment, with 88% of them sharing similar expression
pattern between the atrazine and bentazon treatments. Many genes
related to xenobiotic detoxification and antioxidation, such as cytochrome
P450s, glutathione-S-transferases, superoxide dismutases, catalases,
and tocophero cyclases, were induced by the herbicides. The study
also discovered plants treated with bentazon started to recover between
4 and 8 HAT as reflected in the decreased amplitude of fold changes
of most genes from 4 to 8 HAT. The 12% of the genes that were differentially
expressed between atrazine and bentazon were largely related to cell
recovery, such as genes related to ribosomal components.},
url = {http://plantgenome.scijournals.org/cgi/content/abstract/2/2/191}
}
@ARTICLE{Zhu2010d,
author = {Zhu, James and Weiss, Marcelo and Grubman, Marvin J. and Santos,
Teresa de los},
title = {Differential gene expression in bovine cells infected with wild type
and leaderless foot-and-mouth disease virus},
journal = {Virology},
year = {2010},
volume = {404},
pages = {32--40},
number = {1},
month = aug,
abstract = {The leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV)
plays a critical role in viral pathogenesis. Molecular studies have
demonstrated that Lpro inhibits translation of host capped mRNAs
and transcription of some genes involved in the innate immune response.
We have used microarray technology to study the gene expression profile
of bovine cells infected with wild type (WT) or leaderless FMDV.
Thirty nine out of approximately 22,000 bovine genes were selectively
up-regulated by 2 fold or more in leaderless versus WT virus infected
cells. Most of the up-regulated genes corresponded to IFN-inducible
genes, chemokines or transcription factors. Comparison of promoter
sequences suggested that host factors NF-[kappa]B, ISGF3G and IRF1
specifically contributed to the differential expression, being NF-[kappa]B
primarily responsible for the observed changes. Our results suggest
that Lpro plays a central role in the FMDV evasion of the innate
immune response by inhibiting NF-[kappa]B dependent gene expression.},
issn = {0042-6822},
keywords = {Picornaviruses, FMDV, Microarray, NF-[kappa]B},
url = {http://www.sciencedirect.com/science/article/B6WXR-504TP2M-1/2/33f3af0e132ee7dc30212af7b84bcbe2}
}
@ARTICLE{Zhu2006a,
author = {Zhu, Kun and Choi, Kyoung-Hee and Schweizer, Herbert P. and Rock,
Charles O. and Zhang, Yong-Mei},
title = {Two aerobic pathways for the formation of unsaturated fatty acids
in Pseudomonas aeruginosa},
journal = {Molecular Microbiology},
year = {2006},
volume = {60},
pages = {260--273},
number = {2},
abstract = {Summary The double bond in anaerobic unsaturated fatty acid (UFA)
biosynthesis is introduced by the FabA dehydratase/isomerase of the
bacterial type II fatty acid biosynthetic pathway. A ΔfabA mutant
of Pseudomonas aeruginosa grew aerobically, but required a UFA supplement
for anaerobic growth. Wild-type cells produced 18:1Δ11 as the principal
UFA, whereas the ΔfabA strain produced only 16:1Δ9. The double
bond in the 16:1Δ9 was introduced after phospholipid formation and
was localized in the sn-2 position. Two predicted membrane proteins,
DesA and DesB, possessed the conserved histidine clusters characteristic
of fatty acid desaturases. The ΔfabAΔdesA double mutant required
exogenous fatty acids for growth but the ΔfabAdesB double mutant
did not. Exogenous stearate was converted to 18:1Δ9 and supported
the growth of ΔfabAΔdesA double mutant. A ΔfabAΔdesAdesB triple
mutant was unable to desaturate exogenous stearate and was an UFA
auxotroph. We detected a 2.5-fold increase in desA expression in
ΔfabA mutants, whereas desB expression was derepressed by the deletion
of the gene encoding a transcriptional repressor DesT. These data
add two aerobic desaturases to the enzymes used for fatty acid metabolism
in proteobacteria: DesA, a 2-position phospholipid Δ9-desaturase
that supplements the anaerobic FabA pathway, and DesB, an inducible
acyl-CoA Δ9-desaturase whose expression is repressed by DesT.},
issn = {1365-2958},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1365-2958.2006.05088.x}
}
@ARTICLE{Zhu2009a,
author = {Zhu, Kun and Zhang, Yong-Mei and Rock, Charles O.},
title = {Transcriptional Regulation of Membrane Lipid Homeostasis in Escherichia
coli},
journal = {J. Biol. Chem.},
year = {2009},
volume = {284},
pages = {34880--34888},
number = {50},
month = dec,
abstract = {The biophysical properties of membrane phospholipids are controlled
by the composition of their constituent fatty acids and are tightly
regulated in Escherichia coli. The FabR (fatty acid biosynthesis
repressor) transcriptional repressor controls the proportion of unsaturated
fatty acids in the membrane by regulating the expression of the fabB
({beta}-ketoacyl-ACP synthase I) and fabA ({beta}-hydroxydecanoyl-ACP
dehydratase/isomerase) genes. FabR binding to a DNA palindrome located
within the promoters of the fabB and fabA genes required the presence
of an unsaturated acyl-acyl carrier protein (ACP) or acyl-CoA and
was antagonized by saturated acyl-ACP or acyl-CoA. The FabR-dependent
repression of fabB and fabA by exogenous unsaturated fatty acids
confirmed the role for FabR in responding to the acyl-CoA pool composition,
and the perturbation of the unsaturated:saturated acyl-ACP ratio
using a specific inhibitor of lipid A formation verified FabR-dependent
regulation of fabB by the acyl-ACP composition in vivo. Thus, FabR
plays a key role in controlling the membrane biophysical properties
by regulating gene expression in response to the composition of the
long-chain acyl-thioester pool. This mechanism ensures that a balanced
composition of fatty acids is available for incorporation into the
membrane via the PlsB/PlsC acyltransferases.},
url = {http://www.jbc.org/cgi/content/abstract/284/50/34880}
}
@ARTICLE{Zhu2004,
author = {Zhu, Kathy Q. and Engrav, Loren H. and Tamura, Richard N. and Cole,
Jana A. and Muangman, Pornprom and Carrougher, Gretchen J. and Gibran,
Nicole S.},
title = {Further similarities between cutaneous scarring in the female, red
Duroc pig and human hypertrophic scarring},
journal = {Burns},
year = {2004},
volume = {30},
pages = {518--530},
number = {6},
month = sep,
abstract = {Knowledge of the pathophysiology of hypertrophic scarring following
deep dermal injuries is minimal due to the lack of an animal model.
We previously confirmed that thick scars in female, red Duroc pigs
(FRDP) are similar to human hypertrophic scar. The purpose of this
study was to evaluate TGF[beta]1, IGF-1, decorin, and versican expression
in FRDP wounds. Deep and shallow wounds on the backs of two FRDPs
were studied over 5 months. Immunohistochemistry was performed for
TGF[beta]1, IGF-1, decorin, and versican. TGF[beta]1 and IGF-1 mRNA
were evaluated by in situ hybridization and RT-PCR. In shallow wounds
(1) TGF[beta]1 protein was not detectable and IGF-1 protein was seen
at 10 days post-wounding. TGF[beta]1 and IGF-1 mRNA were elevated
for 30 days. (2) Decorin protein was not detected at 10th day, but
returned to levels of uninjured skin. (3) Versican protein was not
detectable at any time. In deep wounds, (1) TGF[beta]1 and IGF-1
protein and mRNA were elevated early, (2) decorin protein was greatly
reduced for the first 90 days, and (3) versican protein was present
from 30 to 150 days. These findings correlate with findings reported
in the literature for human hypertrophic scar and further validate
the FRDP model of hypertrophic scarring.},
issn = {0305-4179},
keywords = {Burn, Hypertrophic scar, Porcine, Swine, Pig, Duroc, Thermal injury},
url = {http://www.sciencedirect.com/science/article/B6T52-4CVR6KD-4/2/c53d4c819edc4d6677c4eee8622d4353}
}
@ARTICLE{Zhu2011a,
author = {Zhu, Lixin and Baker, Susan S. and Liu, Wensheng and Tao, Meng-Hua
and Patel, Raza and Nowak, Norma J. and Baker, Robert D.},
title = {Lipid in the livers of adolescents with nonalcoholic steatohepatitis:
combined effects of pathways on steatosis},
journal = {Metabolism},
year = {2011},
volume = {60,7},
pages = {1001-1011},
abstract = {Fatty liver is a prerequisite for the development of nonalcoholic
steatohepatitis (NASH). The homeostasis of hepatic lipid is determined
by the dynamic balance of multiple pathways introducing lipids into
or removing lipids from hepatocytes. We aim to study the different
contributions of major lipid pathways to fat deposition in NASH livers.
Expression of the lipid metabolism-related genes was analyzed by
microarray and quantitative real-time polymerase chain reaction analysis.
The expression levels of genes responsible for the rate-limiting
steps of fatty acid uptake (CD36, FABPpm, SLC27A2, and SLC27A5),
de novo synthesis (ACACB), oxidation (CPT-1), and very low-density
lipoprotein (VLDL) secretion (ApoB) were used to evaluate the relative
activity of each pathway. The expression levels for CD36 and CPT-1
were confirmed by Western blot analysis. Fatty acid uptake pathways
were up-regulated to a higher degree than other pathways. The de
novo synthesis pathway was also up-regulated more than both VLDL
secretion and fatty acid oxidation pathways. In contrast to other
NASH livers, one NASH liver exhibited lower ApoB and CPT-1 expression
levels than normal controls. The increased fatty acid uptake and
de novo synthesis were the most common causes for steatosis in NASH
patients. In a rare case, impaired VLDL secretion and fatty acid
oxidation contributed to the development of steatosis. Our study
promises a simple method for the determination of why hepatic steatosis
occurs in individual patients. This method may allow specific targeting
of therapeutic treatments in individual patients.},
issn = {0026-0495},
url = {http://www.sciencedirect.com/science/article/pii/S0026049510003562}
}
@ARTICLE{Zhu2010c,
author = {Zhu, Leilei and Tee, Kang Lan and Roccatano, Danilo and Sonmez, Burcu
and Ni, Ye and Sun, Zhi-Hao and Schwaneberg, Ulrich},
title = {Directed Evolution of an Antitumor Drug (Arginine Deiminase PpADI)
for Increased Activity at Physiological pH},
journal = {Chem. Eur. J. of Chem. Bio.},
year = {2010},
volume = {11},
pages = {691--697},
number = {5},
abstract = {Abstract 10.1002/cbic.200900717.abs Arginine deiminase (ADI; EC 3.5.3.6)
has been studied as a potential antitumor drug for the treatment
of arginine-auxotrophic tumors, such as hepatocellular carcinomas
(HCCs) and melanomas. Studies with human lymphatic leukemia cell
lines confirmed that ADI is an antiangiogenic agent for treating
leukemia. The main limitation of ADI from Pseudomonas plecoglossicida
(PpADI) lies in its pH-dependent activity profile, its pH optimum
is at 6.5. A pH shift from 6.5 to 7.5 results in an approximately
80 % drop in activity. (The pH of human plasma is 7.35 to 7.45.)
In order to shift the PpADI pH optimum, a directed-evolution protocol
based on an adapted citrulline-screening protocol in microtiter-plate
format was developed and validated. A proof of concept for ADI engineering
resulted in a pH optimum of pH 7.0 and increased resistance under
physiological and slightly alkaline conditions. At pH 7.4, variant
M2 (K5T/D44E/H404R) is four times faster than the wild-type PpADI
and retains ~50% of its activity relative to its pH optimum, compared
to ~10% in the case of the wild-type PpADI.},
issn = {1439-7633},
keywords = {antitumor agents, arginine deiminase, directed evolution, leukemia,
pH optimum},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/cbic.200900717}
}
@ARTICLE{Zhu2011b,
author = {Zhu, Min and Yi, Ming and Kim, Chang Hee and Deng, Chuxia and Li,
Yi and Medina, Daniel and Stephens, Robert and Green, Jeffrey},
title = {Integrated miRNA and mRNA expression profiling of mouse mammary tumor
models identifies miRNA signatures associated with mammary tumor
lineage},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R77},
number = {8},
abstract = {BACKGROUND:MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs
involved in regulating gene expression and protein translation. miRNA
expression profiling of human breast cancers has identified miRNAs
related to the clinical diversity of the disease and potentially
provides novel diagnostic and prognostic tools for breast cancer
therapy. In order to further understand the associations between
oncogenic drivers and miRNA expression in sub-types of breast cancer,
we performed miRNA expression profiling on mammary tumors from eight
well-characterized genetically engineered mouse (GEM) models of human
breast cancer, including MMTV-H-Ras, -Her2/neu, -c-Myc, -PymT, -Wnt1
and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1fl/fl;p53+/-;MMTV-cre
knock-out mice and the p53fl/fl;MMTV-cre transplant model.RESULTS:miRNA
expression patterns classified mouse mammary tumors according to
luminal or basal tumor subtypes. Many miRNAs found in luminal tumors
are expressed during normal mammary development. miR-135b, miR-505
and miR-155 are expressed in both basal human and mouse mammary tumors
and many basal-associated miRNAs have not been previously characterized.
miRNAs associated with the initiating oncogenic event driving tumorigenesis
were also identified. miR-10b, -148a, -150, -199a and -486 were only
expressed in normal mammary epithelium and not tumors, suggesting
that they may have tumor suppressor activities. Integrated miRNA
and mRNA gene expression analyses greatly improved the identification
of miRNA targets from potential targets identified in silico.CONCLUSIONS:This
is the first large-scale miRNA gene expression study across a variety
of relevant GEM models of human breast cancer demonstrating that
miRNA expression is highly associated with mammary tumor lineage,
differentiation and oncogenic pathways.},
doi = {10.1186/gb-2011-12-8-r77},
issn = {1465-6906},
pubmedid = {21846369},
url = {http://genomebiology.com/2011/12/8/R77}
}
@ARTICLE{Zhu2005a,
author = {Zhu, Xiaonan and Zeisel, Steven H.},
title = {Gene expression profiling in phosphatidylethanolamine N-methyltransferase
knockout mice},
journal = {Molecular Brain Research},
year = {2005},
volume = {134},
pages = {239--255},
number = {2},
month = apr,
abstract = {Choline is derived from the diet as well as from de novo methylation
of phosphatidylethanolamine catalyzed by phosphatidylethanolamine
N-methyltransferase (PEMT). Pemt knockout mice have no endogenous
synthesis of choline molecules. We previously reported that these
mice have excess S-adenosylmethionine and hypermethylated DNA in
brain, as well as increased mitosis in neural progenitor cells of
the hippocampus in embryonic day 17 (E17) brain. In the present study,
E17 fetal brains and adult brains were harvested and total RNA was
extracted. In fetal brain, using gene expression profiling and Significance
Analysis of Microarrays, we identified 107 significant genes with
increased expression and 379 significant genes with decreased expression.
In adult brain, we identified 381 significant genes with increased
expression and 1037 significant genes with decreased expression.
We observed significant changes in expression of genes regulating
cell cycle (such as TP53, Fgf4, and Ing1), differentiation and neurogenesis
(such as S100A4 and D14Ws), and phospholipid metabolism (such as
Pip5k1a, Pitpn, and Pla2g6) as well as in a number of methyltransferase
genes (including Gnmt). Some genes with expression known to be regulated
by promoter methylation were suppressed in Pemt knockout brain (such
as S100a4 and TP53). These findings are consistent with the biochemical
changes that we previous reported in fetal brains from Pemt knockout
mice. This is the first report of gene profiling in Pemt-/- mouse
brain.},
issn = {0169-328X},
keywords = {PEMT, Brain, Mouse, Choline, Gene expression profiling},
url = {http://www.sciencedirect.com/science/article/B6T07-4FG89CN-1/2/8c9b2bb8b04d11c8d9eb771fddbcb1e9}
}
@ARTICLE{Zhu2008a,
author = {Zhu, Yaohong and Magnusson, Ulf and Fossum, Caroline and Berg, Mikael},
title = {Escherichia coli inoculation of porcine mammary glands affects local
mRNA expression of Toll-like receptors and regulatory cytokines},
journal = {Veterinary Immunology and Immunopathology},
year = {2008},
volume = {125},
pages = {182--189},
number = {1-2},
month = sep,
abstract = {The expression of mRNAs for the Toll-like receptors (TLRs) TLR2 and
TLR4, pro- and anti inflammatory cytokines and their receptors was
evaluated in mammary gland biopsy material collected from sows intramammarily
inoculated with Escherichia coli strain O127 at parturition. Quantitative
real-time RT-PCR analysis showed increased mRNA levels for TLR2,
the proinflammatory cytokines interleukin IL-1[beta] and tumor necrosis
factor-alpha TNF-[alpha], and the anti-inflammatory cytokine IL-10
in the inoculated mammary glands 24 h after inoculation. Increased
mRNA levels of the proinflammatory cytokine IL-6 were only observed
in the inoculated mammary glands of sows that developed clinical
signs of mastitis. In contrast, the expression of the anti-inflammatory
cytokine, transforming growth factor-beta 1 (TGF-[beta]1) mRNA was
unaltered, as was mRNA expression for the IL-1 receptor type I (IL-1R1).
Furthermore, IL-1[beta] and IL-10 mRNA expression was higher in the
inoculated mammary glands of sows that developed clinical signs of
mastitis compared with sows that remained clinically healthy. Notably,
sows that developed clinical signs of mastitis had significantly
lower pre-inoculation levels of IL-1[beta] mRNA than sows that remained
clinically healthy. These findings suggest that development of coliform
mastitis is associated with the level of local expression of regulatory
cytokines in response to intramammary E. coli inoculation and infection.},
issn = {0165-2427},
keywords = {Cytokine, Toll-like receptor, Real-time RT-PCR, Pig, Escherichia coli},
url = {http://www.sciencedirect.com/science/article/B6TD5-4SFXK3T-2/2/215bcca1dd82b2cb0cfe030db74cda77}
}
@ARTICLE{Zhu2010b,
author = {Zhu, Yuan and Valter, Krisztina and Stone, Jonathan},
title = {Environmental Damage to the Retina and Preconditioning: Contrasting
Effects of Light and Hyperoxic Stress},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {4821--4830},
number = {9},
month = sep,
abstract = {Purpose.Environmental stress (bright light, hypoxia) can "condition"
retinal photoreceptors, increasing their resistance to subsequent
stress. The present study tests whether another photoreceptor-lethal
stress, hyperoxia, can induce similar resistance. Methods.Vulnerability
to hyperoxia was tested in young adult C57BL/6J mice exposed to 1000
lux cyclic light for 1 week or to 50% O2 for 1 week and then to 75%
O2 for 2 weeks. Vulnerability to light was tested in Balb/cJ mice
exposed to 300 lux cyclic light for 2 days or to 75% O2 for 2 weeks
and then to 1000 lux cyclic light for 1 week. Retinas were analyzed
for photoreceptor death, levels of stress-related proteins (GFAP,
FGF-2, MnSOD, acrolein), and the regulation of candidate neuroprotective
genes (HSP70.1, Ledgf, FGF-13, Timp2). Results.Light preconditioning
did not cause measurable death of photoreceptors but reduced photoreceptor
death induced by subsequent hyperoxic or light stress, reduced levels
of stress-related proteins, and maintained the length and organization
of photoreceptor outer segments. Hyperoxic preconditioning caused
measurable cell death but provided no protection against subsequent
hyperoxic or light stress. Of the four candidate neuroprotective
proteins examined, the regulation of only one (Timp2) seemed associated
with the neuroprotection observed. Conclusions.Light preconditioning,
causing only minimal damage to photoreceptors, induced protection
against subsequent stress from both hyperoxia and light. By contrast,
hyperoxic preconditioning caused measurable photoreceptor damage
but induced no protection against light or hyperoxia. These data
suggest a separation between stress-induced damage to photoreceptors
and the upregulation of protective mechanisms, encouraging the search
for ways to protect the retina without damaging it.},
url = {http://www.iovs.org/cgi/content/abstract/51/9/4821}
}
@ARTICLE{Zhu2012,
author = {Zaifang Zhu and Joann J. Lu and Shaorong Liu},
title = {Protein separation by capillary gel electrophoresis: A review},
journal = {Analytica Chimica Acta},
year = {2012},
volume = {709},
pages = {21 - 31},
number = {0},
abstract = {Capillary gel electrophoresis (CGE) has been used for protein separation
for more than two decades. Due to the technology advancement, current
CGE methods are becoming more and more robust and reliable for protein
analysis, and some of the methods have been routinely used for the
analysis of protein-based pharmaceuticals and quality controls. In
light of this progress, we survey 147 papers related to CGE separations
of proteins and present an overview of this technology. We first
introduce briefly the early development of CGE. We then review the
methodology, in which we specifically describe the matrices, coatings,
and detection strategies used in CGE. CGE using microfabricated channels
and incorporation of CGE with two-dimensional protein separations
are also discussed in this section. We finally present a few representative
applications of CGE for separating proteins in real-world samples.},
doi = {10.1016/j.aca.2011.10.022},
issn = {0003-2670},
keywords = {Capillary gel electrophoresis},
url = {http://www.sciencedirect.com/science/article/pii/S0003267011013328}
}
@ARTICLE{Zhu-Shimoni2009,
author = {Zhu-Shimoni, Judith and Gunawan, Feny and Thomas, Anne and Vanderlaan,
Martin and Stults, John},
title = {Trace level analysis of leached Protein A in bioprocess samples without
interference from the large excess of rhMAb IgG},
journal = {Journal of Immunological Methods},
year = {2009},
volume = {341},
pages = {59--67},
number = {1-2},
month = feb,
abstract = {Resins containing immobilized Staphylococcal Protein A (PA) are widely
used in the commercial purification of recombinant human monoclonal
antibody (rhuMAb IgG) biotherapeutics. Therefore, a sensitive assay
for leached PA is needed to ensure that PA is not present at unacceptable
levels as an impurity in the final product. PA impurities are measured
by an ELISA using chicken anti-PA antibodies. However, PA in the
presence of IgG product forms a PA/IgG complex that interferes in
the assay. In this report a multi-product PA ELISA is described,
wherein the PA/IgG complex is dissociated by heating in the presence
of detergents and chelators prior to the ELISA. The dissociation
facilitates the accessibility of the anti-PA antibodies to bind to
PA in the immunoassay. Heat is provided by a novel microwave technology
which allows brief heating time and high sample throughput using
a microtiter plate for sample heating. Thus, broadly applicable dissociation
conditions, suitable for all 21 rhMab IgGs tested to date were identified.
This approach streamlines the measurement of leached PA, allows higher
sample testing throughput, facilitates application across multiple
products, and facilitates assay automation. Data comparing in-process
samples tested with both the former product-specific ELISA and this
new multi-product assay are shown.},
issn = {0022-1759},
keywords = {Staphylococcal protein A, PA/IgG complex dissociation, Microwave,
Multi-product PA ELISA},
url = {http://www.sciencedirect.com/science/article/B6T2Y-4V16CNH-1/2/eb4688225d8e2624e1b6abcc8af4f8cd}
}
@ARTICLE{Zhuang2011,
author = {Zhuang, Wei-Qin and Yi, Shan and Feng, Xueyang and Zinder, Stephen
H. and Tang, Yinjie J. and Alvarez-Cohen, Lisa},
title = {Selective Utilization of Exogenous Amino Acids by Dehalococcoides
ethenogenes Strain 195 and Its Effects on Growth and Dechlorination
Activity},
journal = {Appl. Envir. Microbiol.},
year = {2011},
volume = {77},
pages = {7797-7803},
number = {21},
abstract = {Bacteria of the genus Dehalococcoides are important members of bioremediation
communities because of their ability to detoxify chloroethenes to
the benign end product ethene. Genome-enabled studies conducted with
Dehalococcoides ethenogenes 195 have revealed that two ATP-binding
cassette (ABC)-type amino acid transporters are expressed during
its exponential growth stages. In light of previous findings that
Casamino Acids enhanced its dechlorination activity, we hypothesized
that strain 195 is capable of importing amino acids from its environment
to facilitate dechlorination and growth. To test this hypothesis,
we applied isotopomer-based dilution analysis with 13C-labeled acetate
to differentiate the amino acids that were taken up by strain 195
from those synthesized de novo and to determine the physiological
changes caused by the significantly incorporated amino acids. Our
results showed that glutamate/glutamine and aspartate/asparagine
were almost exclusively synthesized by strain 195, even when provided
in excess in the medium. In contrast, phenylalanine, isoleucine,
leucine, and methionine were identified as the four most highly incorporated
amino acids, at levels >30% of respective proteinogenic amino acids.
When either phenylalanine or all four highly incorporated amino acids
were added to the defined mineral medium, the growth rates, dechlorination
activities, and yields of strain 195 were enhanced to levels similar
to those observed with supplementation with 20 amino acids. However,
genes for the putative ABC-type amino acids transporters and phenylalanine
biosynthesis exhibited insignificant regulation in response to the
imported amino acids. This study also demonstrates that using isotopomer-based
metabolite analysis can be an efficient strategy for optimizing nutritional
conditions for slow-growing microorganisms.},
doi = {10.1128/AEM.05676-11},
eprint = {http://aem.asm.org/cgi/reprint/77/21/7797.pdf},
url = {http://aem.asm.org/cgi/content/abstract/77/21/7797}
}
@ARTICLE{Zidar2011,
author = {Zidar, Nina and Bostjancic, Emanuela and Gale, Nina and Kojc, Nika
and Poljak, Mario and Glavac, Damjan and Cardesa, Antonio},
title = {Down-regulation of microRNAs of the miR-200 family and miR-205, and
an altered expression of classic and desmosomal cadherins in spindle
cell carcinoma of the head and neck--hallmark of epithelial-mesenchymal
transition},
journal = {Human Pathology},
year = {2011},
volume = {42},
pages = {482--488},
number = {4},
month = apr,
abstract = {Summary MicroRNAs are small, noncoding RNAs that regulate gene expression
by posttranscriptional regulation of target genes. miR-200 family
and miR-205 have been shown experimentally to regulate epithelial-mesenchymal
transition. As epithelial-mesenchymal transition is the postulated
pathogenetic mechanism in spindle cell carcinoma, we analyzed the
expression of these microRNAs in spindle cell carcinoma of the head
and neck in comparison to conventional squamous cell carcinoma of
similar location and stage. We also analyzed the expression of classic
and desmosomal cadherins, which are believed to be important targets
during epithelial-mesenchymal transition. Forty-five cases of spindle
cell carcinoma and 45 cases of squamous cell carcinoma of the head
and neck were analyzed using real-time polymerase chain reaction
for microRNAs, and immunohistochemistry for classic cadherins (E-
and N-cadherins) and desmosomal cadherins. We found a significant
down-regulation of the miR-200 family and miR-205, loss of desmosomal
cadherins, and an altered expression of classic cadherins in spindle
cell carcinoma in comparison to squamous cell carcinoma. Down-regulation
of the miR-200 family and miR-205 strongly supports the postulated
role of epithelial-mesenchymal transition in spindle cell carcinoma.
These microRNAs act on transcription repressors that were also up-regulated
in our cases of spindle cell carcinoma, both on mRNA and on protein
levels. The result is not only an altered expression of classic cadherins
in adherens junctions but also a complete loss of desmosomal cadherins.},
issn = {0046-8177},
keywords = {Spindle cell carcinoma, Pathogenesis, Desmosomes, Adherens junction,
Transcription repression, Epithelial-mesenchymal transition, MicroRNA},
url = {http://www.sciencedirect.com/science/article/pii/S0046817710003552}
}
@ARTICLE{Zidar2009,
author = {Zidar, Nina and Odar, Katarina and Glavac, Damjan and Jerse, Maja
and Zupanc, Tomaz and Stajer, Dusan},
title = {Cyclooxygenase in normal human tissues – is COX-1 really a constitutive
isoform, and COX-2 an inducible isoform?},
journal = {Journal of Cellular and Molecular Medicine},
year = {2009},
volume = {13},
pages = {3753--3763},
number = {9b},
abstract = {Abstract Cyclooxygenase (COX) is a key enzyme in prostanoid synthesis.
It exists in two isoforms, COX-1 and COX-2. COX-1 is referred to
as a ‘constitutive isoform’, and is considered to be expressed
in most tissues under basal conditions. In contrast, COX-2 is referred
to as an ‘inducible isoform’, which is believed to be undetectable
in most normal tissues, but can be up-regulated during various conditions,
many of them pathological. Even though the role of COX in homeostasis
and disease in now well appreciated, controversial information is
available concerning the distribution of COX isoforms in normal human
tissues. There is mounting evidence that it is much more complex
than generally believed. Our aim was therefore to analyse the expression
and distribution of COX isoforms in normal human tissues, using immunohistochemistry,
Western blotting and real-time RT-PCR. Autopsy samples from 20 healthy
trauma victims and samples from 48 biopsy surgical specimens were
included. COX-1 was found in blood vessels, interstitial cells, smooth
muscle cells, platelets and mesothelial cells. In contrast, COX-2
was found predominantly in the parenchymal cells of many tissues,
with few exceptions, for example the heart. Our results confirm the
hypothesis that the distribution of COX isoforms in healthy tissues
is much more complex than generally believed. This and previous studies
indicate that both isoforms, not only COX-1, are present in many
normal human tissues, and that both isoforms, not only COX-2, are
up-regulated in various pathological conditions. We may have to revise
the concept of ‘constitutive’ and ‘inducible’ COX isoforms.},
issn = {1582-4934},
keywords = {cyclooxygenase, isoforms, constitutive, inducible, normal tissue,
distribution},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1582-4934.2008.00430.x}
}
@ARTICLE{Zidek2007,
author = {Zidek, Nadine and Hellmann, Juergen and Kramer, Peter-Juergen and
Hewitt, Philip G.},
title = {Acute Hepatotoxicity: A Predictive Model Based on Focused Illumina
Microarrays},
journal = {Toxicol. Sci.},
year = {2007},
volume = {99},
pages = {289--302},
number = {1},
month = sep,
abstract = {Drug-induced hepatotoxicity is a major issue for drug development,
and toxicogenomics has the potential to predict toxicity during early
toxicity screening. A bead-based Illumina oligonucleotide microarray
containing 550 liver specific genes has been developed. We have established
a predictive screening system for acute hepatotoxicity by analyzing
differential gene expression profiles of well-known hepatotoxic and
nonhepatotoxic compounds. Low and high doses of tetracycline, carbon
tetrachloride (CCL4), 1-naphthylisothiocyanate (ANIT), erythromycin
estolate, acetaminophen (AAP), or chloroform as hepatotoxicants,
clofibrate, theophylline, naloxone, estradiol, quinidine, or dexamethasone
as nonhepatotoxic compounds, were administered as a single dose to
male Sprague-Dawley rats. After 6, 24, and 72 h, livers were taken
for histopathological evaluation and for analysis of gene expression
alterations. All hepatotoxic compounds tested generated individual
gene expression profiles. Based on leave-one-out cross-validation
analysis, gene expression profiling allowed the accurate discrimination
of all model compounds, 24 h after high dose treatment. Even during
the regeneration phase, 72 h after treatment, CCL4, ANIT, and AAP
were predicted to be hepatotoxic, and only these three compounds
showed histopathological changes at this time. Furthermore, we identified
64 potential marker genes responsible for class prediction, which
reflected typical hepatotoxicity responses. These genes and pathways,
commonly deregulated by hepatotoxicants, may be indicative of the
early characterization of hepatotoxicity and possibly predictive
of later hepatotoxicity onset. Two unknown test compounds were used
for prevalidating the screening test system, with both being correctly
predicted. We conclude that focused gene microarrays are sufficient
to classify compounds with respect to toxicity prediction.},
url = {http://toxsci.oxfordjournals.org/cgi/content/abstract/99/1/289}
}
@ARTICLE{Ziegler2011,
author = {Ziegler, Christina and Goldmann, Oliver and Hobeika, Elias and Geffers,
Robert and Peters, Georg and Medina, Eva},
title = {The dynamics of T cells during persistent Staphylococcus aureus infection:
from antigen-reactivity to in vivo anergy},
journal = {EMBO Molecular Medicine},
year = {2011},
volume = {3},
pages = {652--666},
number = {11},
abstract = {Staphylococcus aureus is an important human pathogen that can cause
long-lasting persistent infections. The mechanisms by which persistent
infections are maintained involve both bacterial escape strategies
and modulation of the host immune response. So far, the investigations
in this area have focused on strategies used by S. aureus to persist
within the host. Here, we used an experimental mouse model to investigate
the host response to persistent S. aureus infection. Our results
demonstrated that T cells, which are critical for controlling S.
aureus infection, gradually lost their ability to respond to antigenic
stimulation and entered a state of anergy with the progression of
infection towards persistence. The T cell hyporesponsiveness was
reverted by co-stimulation with the phorbol ester PMA, an activator
of protein kinase C, suggesting that a failure in the T cell receptor
(TCR)-proximal signalling events underlie the hyporesponsive phenotype.
The presence of these anergic antigen-specific T cells may contribute
to the failure of the host immune response to promote sterilizing
immunity during persistent S. aureus infection and also offers new
possibilities for novel immunotherapeutic approaches.},
doi = {10.1002/emmm.201100173},
issn = {1757-4684},
keywords = {immunosuppressive mechanisms, persistent infection, Staphylococcus
aureus, T cell anergy, T cell responses},
publisher = {WILEY-VCH Verlag},
url = {http://dx.doi.org/10.1002/emmm.201100173}
}
@ARTICLE{Ziegler2010,
author = {Ziegler, Lina and Segal-Ruder, Yael and Coppola, Giovanni and Reis,
Arbel and Geschwind, Daniel and Fainzilber, Mike and Goldstein, Ronald
S.},
title = {A human neuron injury model for molecular studies of axonal regeneration},
journal = {Experimental Neurology},
year = {2010},
volume = {223},
pages = {119--127},
number = {1},
month = may,
abstract = {The enhancement of regeneration of damaged axons in both the peripheral
and central nervous systems is a widely pursued goal in clinical
medicine. Although some of the molecular mechanisms involved in the
intrinsic neurite regeneration program have been elucidated, much
additional study is required for development of new therapeutics.
The majority of studies in the field of axonal regeneration have
utilized animal models due to obvious limitations of the accessibility
of human neural tissues. Here we describe the use of human embryonic
stem cell (hESC)-derived neurons as a novel model for studying neuronal
responses to axonal injury. Neurons were generated using PA6 induction
and neurites injured in vitro using trituration or laser microdissection.
Lesioned neurons re-extended neurites with distinct growth cones.
Expression of proteins associated with regeneration were observed
in this human in vitro system, including appearance of importin [beta]1
in processes after neuritomy. Laser-transected hESC-derived neuronal
cultures were analyzed for their transcriptional response to injury
using Affymetrix expression microarrays. Profound changes in gene
expression were observed over a time course of 2 to 24 hours after
lesion. The expression of several genes reported to be involved in
axonal injury responses in animal models changed following injury
of hESC-derived neurons. Thus, hESC-derived neurons may be a useful
in vitro model system for mechanistic studies on human axonal injury
and regeneration.},
booktitle = {Regeneration in the Peripheral Nervous System},
issn = {0014-4886},
keywords = {Axon regeneration, Sensory neuron, Microarray, Human embryonic stem
cells},
url = {http://www.sciencedirect.com/science/article/B6WFG-4XC9SFS-1/2/87dbfe78ffbe7d0403fedfa85caa61f1}
}
@ARTICLE{ZIEGLSCHMID2005,
author = {ZIEGLSCHMID, VEIT and HOLLMANN, CHRISTIANE and GUTIERREZ, BERTHA
and ALBERTI, WINFIRED and STROTHOFF, DARK and GROSS, EBERHARD and
BOCHER, OLIVER},
title = {Combination of Immunomagnetic Enrichment with Multiplex RT-PCR Analysis
for the Detection of Disseminated Tumor Cells},
journal = {Anticancer Res},
year = {2005},
volume = {25},
pages = {1803--1810},
number = {3A},
month = may,
abstract = {Background: A highly specific and sensitive tumor cell detection assay
is reported, which combines immunomagnetic enrichment with multiplex
RT-PCR analysis. Materials and Methods: The effect on the recovery
rate of breast, testicular and colorectal cancer cells using single
antibodies and combinations of them for IMS was examined by fluorescence
microscopy and multiplex RT-PCR. The clinical utility of a tumor
cell detection assay using IMS with multiplex RT-PCR was tested by
examination of colorectal cancer blood samples and by comparing the
results with CEA serum protein levels. Results: A combination of
antibodies for IMS and multiplex RT-PCR analysis proved to be the
most sensitive approach for detection of tumor cells in peripheral
blood with a detection limit of two tumor cells. The examination
of blood of colorectal cancer patients by using a multiplex RT-PCR
assay in comparison with CEA serum protein levels indicated a distinct
advantage of the former over the latter with respect to a more reliable
prediction of an ongoing metastatic process. Conclusion: The results
indicate that a combination of antibodies for immunomagnetic enrichment
with multiplex RT-PCR analysis detects disseminated tumor cells with
high sensitivity and specificity, thus indicating a metastatic process
several months earlier compared to CEA serum protein level measurements.
This assay might be valuable for prognosis in cancer.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/25/3A/1803}
}
@ARTICLE{ZIEGLSCHMID2007,
author = {ZIEGLSCHMID, VEIT and HOLLMANN, CHRISTIANE and GUTIERREZ, BERTHA
and KREHAN, ANDREAS and KAUL, SEPP and BOCHER, OLIVER},
title = {Heterogeneous Expression of Tumor-associated Genes in Disseminated
Breast Cancer Cells},
journal = {Anticancer Res},
year = {2007},
volume = {27},
pages = {1769--1776},
number = {4A},
month = jul,
abstract = {Background: Gene expression profiles were determined to demonstrate
heterogeneity of viable disseminated tumor cells (DTC) in the blood
of breast cancer patients. Patients and Methods: All patients (n=48)
suffered from metastatic disease (M1) and were treated with chemotherapy
and/or Herceptin(R), respectively. Blood samples were analyzed by
a DTC detection assay consisting of immunomagnetic tumor cell selection
combined with expression profiling of the tumor-associated transcripts
GA733-2, MUC-1, HER-2 and Claudin-7. In addition, the correlation
of HER-2 expression in DTC with histopathologically determined HER-2
status in distant metastases and primary tumors in selected cases
was investigated. Results: DTC were detected in 69% (p<0.0001) of
breast cancer patients. The expression profiles were shown to be
heterogeneous within different patients and even within the follow-up
period of patients, reflecting the expected heterogeneity of DTC.
Furthermore, preliminary results showed a correlation between HER-2
gene expression in DTC and HER-2 overexpression in tumor tissue of
distant metastases. Conclusion: The results suggest a clinical value
of the DTC detection assay with respect to a more precise characterization
of individual cancer disease and selection for therapy. More emphasis
should be placed on HER-2 expression in DTC as a possible precursor
of distant metastases.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/27/4A/1769}
}
@ARTICLE{ZIEGLSCHMID2007a,
author = {ZIEGLSCHMID, VEIT and HOLLMANN, CHRISTIANE and MANNEL, JENNY and
ALBERT, WINFRIED and JAESCHKE-MELLI, STEFAN and ECKSTEIN, BIRTE and
HILLEMANN, TINA and GRETEN, TIM F. and GROSS, EBERHARD and BOCHER,
OLIVER},
title = {Tumor-associated Gene Expression in Disseminated Tumor Cells Correlates
with Disease Progression and Tumor Stage in Colorectal Cancer},
journal = {Anticancer Res},
year = {2007},
volume = {27},
pages = {1823--1832},
number = {4A},
month = jul,
abstract = {Background: A possible correlation of disease progression and tumor
stage in colorectal cancer patients with tumor-associated gene expression
in disseminated tumor cells (DTC) was evaluated. Detection of DTC
and expression of tumor-associated genes might be of clinical value
with respect to individual patient prognosis, monitoring of therapy
and as a surrogate tumor staging parameter. Patients and Methods:
In a multicenter study, a total of 196 peripheral blood samples were
collected from 76 patients with tumor stage Dukes' A to D and analyzed
using a DTC detection assay consisting of immunomagnetic selection
and expression analysis of the tumor-associated genes CEA, EGFR and
GA733-2. DTC detection rates were assessed prior to surgery and post
surgery in patients with tumor stage Dukes' A, B and C, and compared
with results in metastatic patients. CEA serum protein levels were
determined and compared with DTC and CEA expression, respectively.
Results: In a comparison analysis, EGFR and CEA expression was detected
in 88% (p=0.001) and 0% (p=0.002) prior to surgery, in 66% (p=0.001)
and 20% (p=0.002) post surgery, as well as in 15% (p<0.0001) and
66% (p<0.0001) of blood samples collected from metastatic patients,
respectively. Expression of tumor-associated genes in DTC prior to
surgery and in follow-up samples indicated an ongoing metastatic
process. DTC detection rates in patients with Dukes' A (14%), Dukes'
B (13%) and Dukes' C (40%) prior to surgery correlated statistically
with the expected recurrence rate. There was no correlation between
DTC expressing CEA and elevation of CEA serum protein levels. Conclusion:
EGFR and CEA gene expression correlated with disease progression
and tumor stage. Detection of CEA expression in DTC might have a
predictive value in colorectal cancer and may help to identify patients
at a greater risk of relapse. DTC in peripheral blood collected prior
to surgery as well as in follow-up samples have a prognostic clinical
value.},
url = {http://ar.iiarjournals.org/cgi/content/abstract/27/4A/1823}
}
@ARTICLE{Ziehr2010,
author = {Ziehr, David R. and Ellis, Jamie P. and Culviner, Peter H. and Cavagnero,
Silvia},
title = {Production of Ribosome-Released Nascent Proteins with Optimal Physical
Properties},
journal = {Analytical Chemistry},
year = {2010},
volume = {82},
pages = {4637-4643},
number = {11},
note = {PMID: 20397641},
doi = {10.1021/ac902952b},
eprint = {http://pubs.acs.org/doi/pdf/10.1021/ac902952b},
url = {http://pubs.acs.org/doi/abs/10.1021/ac902952b}
}
@ARTICLE{Zielinski2010,
author = {Zielinski, Anne J. and Fong, Sylvia and Allison, Juanita and Kawahara,
Misako and Coppe, Jean-Philippe and Feiler, Heidi and Lee, Nancy
M. and Desprez, Pierre-Yves},
title = {The helix-loop-helix Id-1 inhibits PSA expression in prostate cancer
cells},
journal = {Int. J. Cancer},
year = {2010},
volume = {126},
pages = {2490--2496},
number = {10},
abstract = {Abstract 10.1002/ijc.24811.abs The inhibitor of basic helix-loop-helix
transcription factors, Id-1, is an important gene whose expression
increases during prostate cancer progression and that upregulates
proliferation, migration and invasion. We used microarray analysis
to identify the downstream genes whose transcriptional expression
is modulated by Id-1 protein. We compared gene expression in control
LNCaP cells and Id-1-transduced LNCaP cells, which become significantly
more aggressive after Id-1 overexpression, thus mimicking the high
levels of Id-1 detected in metastatic cell lines. We used the Affy
HTA U133A Expression Arrays with 45,000 probe sets representing more
than 39,000 transcripts. We found that one of the most significantly
downregulated genes on Id-1 expression was kallikrein 3 [also called
prostate specific antigen (PSA)], the most commonly used biomarker
of prostate cancer. Here, we show that the reduction in PSA mRNA
and protein expression associated with high-grade prostate cancers,
which generally express high levels of Id-1, could be the consequence
of Id-1 overexpression.},
issn = {1097-0215},
keywords = {transcriptional regulator, prostate specific antigen, prostate acid
phosphatase, androgen receptor},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/ijc.24811}
}
@ARTICLE{Zietarska2007,
author = {Zietarska, Magdalena and Maugard, Christine M. and Filali-Mouhim,
Abdelali and Alam-Fahmy, Mona and Tonin, Patricia N. and Provencher,
Diane M. and Mes-Masson, Anne-Marie},
title = {Molecular description of a 3D in vitro model for the study of epithelial
ovarian cancer (EOC)},
journal = {Mol. Carcinog.},
year = {2007},
volume = {46},
pages = {872--885},
number = {10},
abstract = {Abstract 10.1002/mc.20315.abs Epithelial ovarian cancer (EOC) cell
lines are useful tools for the molecular and biological characterization
of ovarian cancer. The use of an in vitro multidimensional (3-D)
culture model recapitulates some of the growth conditions encountered
by tumor cells in vivo. Here we describe a molecular comparison of
spheroid based 3D EOC models versus monolayer cultures and xenografts
using cell lines from malignant ovarian tumors (TOV-21G and TOV-112D)
and ascites (OV-90) previously established and characterized in our
laboratory. Gene expression analyses of the three models were performed
using the Affymetrix HG-U133A high density DNA array. Cluster analysis
identified a set of genes that stratified expression profiles from
the EOC cell lines grown as spheroids and xenografts from that of
monolayer cultures. The gene expression analysis results were validated
by Q-PCR analyses on an independent set of RNAs. Differential expression
observed for the S100A6 gene between the monolayer, spheroid cultures
and xenografts was confirmed at the protein level by immunohistochemistry.
The analysis was extended to various ovarian tumor tissues using
an EOC tissue array. This result represents an example of a gene
that, if studied in vitro, is more representative of the in vivo
disease in a 3D model rather than the monolayer culture. Identification
of genes in spheroid models that mimic the in vivo tumor gene expression
patterns may allow a better understanding of the community effect
observed in human disease that is determined by direct or indirect
interactions of cells with their environment or other surrounding
cells. © 2007 Wiley-Liss, Inc.},
issn = {1098-2744},
keywords = {ovarian cancer cell lines, spheroid cultures, expression microarray,
tissue array},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/mc.20315}
}
@ARTICLE{Zijl2011,
author = {van Zijl, Franziska and Mall, Sabine and Machat, Georg and Pirker,
Christine and Zeillinger, Robert and Weinhaeusel, Andreas and Bilban,
Martin and Berger, Walter and Mikulits, Wolfgang},
title = {A Human Model of Epithelial to Mesenchymal Transition to Monitor
Drug Efficacy in Hepatocellular Carcinoma Progression},
journal = {Mol. Cancer Ther.},
year = {2011},
volume = {10},
pages = {850--860},
number = {5},
month = may,
abstract = {The epithelial to mesenchymal transition (EMT) of malignant hepatocytes
is a crucial event in hepatocellular carcinoma (HCC) progression
and recurrence. We aimed to establish a human model of EMT to examine
drug efficacy and specificity in HCC progression. Human HCC cell
populations were characterized by immunofluorescence analysis, migration
and invasion assays, array comparative genomic hybridization, whole-genome
expression profiling, and promoter methylation. Therapeutic agents
clinically used against HCC were examined for efficacy by determination
of IC50 values. We show that liver cancer cell lines exhibited either
an epithelial or mesenchymal phenotype of which the latter showed
strong migratory and invasive abilities in vitro. The common cellular
origin of both cell types indicated that mesenchymal HCC cells have
been derived from epithelial hepatocytes through EMT in the HCC patient.
Drug exposure of mesenchymal HCC cells showed higher resistance to
the targeted therapeutic agents sorafenib and erlotinib as compared
to epithelial HCC cells, which were slightly more resistant to cytostatic
drugs. Most remarkably, combined treatment with doxorubicin and sorafenib
caused increased susceptibility of both HCC cell types resulting
in enhanced drug efficacy. Taken together, this EMT model of human
HCC allows the identification of molecular mechanisms and the assessment
of therapeutic drug efficacy during liver cancer progression in preclinical
studies. Mol Cancer Ther; 10(5); 850-60. (C)2011 AACR.},
comment = {10.1158/1535-7163.MCT-10-0917},
url = {http://mct.aacrjournals.org/cgi/content/abstract/10/5/850}
}
@ARTICLE{Zikova2010,
author = {Zikova, Andrea and Trubiroha, Achim and Wiegand, Claudia and Wuertz,
Sven and Rennert, Bernhard and Pflugmacher, Stephan and Kopp, Radovan
and Mares, Jan and Kloas, Werner},
title = {Impact of microcystin containing diets on physiological performance
of Nile tilapia (Oreochromis niloticus) concerning stress and growth},
journal = {Environmental Toxicology and Chemistry},
year = {2010},
volume = {29},
pages = {561--568},
number = {3},
abstract = {Abstract 10.1002/etc.76.abs Diets containing Microcystis with considerable
amounts of the cyanotoxin microcystin-LR (MC-LR) were fed to determine
their impact on the physiological performance of the omnivorous Nile
tilapia (Oreochromis niloticus) with regard to stress and growth
performance. Four different diets were prepared based on a commercial
diet (control, MC-5% [containing 5% dried Microcystis biomass], MC-20%
[containing 20% dried Microcystis biomass], and Arthrospira-20% [containing
20% dried Arthrospira sp. biomass without toxin]) and fed to female
Nile tilapia. Blood and tissue samples were taken after 1, 7, and
28 d, and MC-LR was quantified in gills, muscle, and liver by using
high-performance liquid chromatography (HPLC). Only in the liver
were moderate concentrations of MC-LR detected. The stress hormone
cortisol and glucose were analyzed from plasma, suggesting that all
modified diets caused only minor to moderate stress, which was confirmed
by analyses of hepatic glycogen. In addition, the effects of the
different diets on growth performance were investigated by determining
gene expression of hypophyseal growth hormone (GH) and hepatic insulin-like
growth factor-I (IGF-I). For all diets, quantitative reverse transcription-polymerase
chain reaction (RT-qPCR) demonstrated no significant effect on gene
expression of the major endocrine hormones of the growth axis, whereas
classical growth data, including growth and feed conversion ratio,
displayed slight inhibitory effects of all modified diets independent
of their MC-LR content. However, no significant change was found
in condition or hepatosomatic index among the various diets, so it
seems feasible that dried cyanobacterial biomass might be even used
as a component in fish diet for Nile tilapia, which requires further
research in more detail. Environ. Toxicol. Chem. 2010;29:561–568.
© 2009 SETAC},
issn = {1552-8618},
keywords = {Microcystin-LR, Fish diet, Tilapia, Stress, Growth},
publisher = {John Wiley \& Sons, Inc.},
url = {http://dx.doi.org/10.1002/etc.76}
}
@ARTICLE{Zilliox2007,
author = {Zilliox, Michael J. and Moss, William J. and Griffin, Diane E.},
title = {Gene Expression Changes in Peripheral Blood Mononuclear Cells during
Measles Virus Infection},
journal = {Clin. Vaccine Immunol.},
year = {2007},
volume = {14},
pages = {918--923},
number = {7},
month = jul,
abstract = {Measles virus continues to cause morbidity and mortality despite the
existence of a safe and efficacious vaccine. Measles is associated
with induction of both a long-lived protective immune response and
immunosuppression. To gain insight into immunological changes during
measles virus infection, we examined gene expression in blood mononuclear
cells from children with acute measles and children in the convalescent
phase compared to uninfected control children. There were 13 significantly
upregulated and 206 downregulated genes. Upregulated genes included
the immune regulatory molecules interleukin 1{beta} (IL-1{beta}),
CIAS-1, tumor necrosis factor alpha, PDE4B, PTGS2, IL-8, CXCL2, CCL4,
ICAM-1, CD83, GOS-2, IER3 (IEX-1), and TNFAIP3 (A20). Plasma levels
of IL-1{beta} and IL-8 were elevated during measles virus infection.
Downregulated genes mainly involved three gene ontology biological
processes, transcription, signal transduction, and the immune response,
and included IL-16 and cell surface receptors IL-4R, IL-6R, IL-7R,
IL-27RA, CCR2, and CCR7. Most mRNAs had not returned to control values
1 month after discharge, consistent with prolonged immune response
abnormalities during measles virus infection.},
url = {http://cvi.asm.org/cgi/content/abstract/14/7/918}
}
@ARTICLE{Zimmer2011a,
author = {Zimmer, Karin E. and Kraugerud, Marianne and Aleksandersen, Mona
and Gutleb, Arno C. and Østby, Gunn C. and Dahl, Ellen and Berg,
Vidar and Skaare, Janneche U. and Olsaker, Ingrid and Ropstad, Erik},
title = {Fetal adrenal development: Comparing effects of combined exposures
to PCB 118 and PCB 153 in a sheep model},
journal = {Environmental Toxicology},
year = {2011},
pages = {n/a--n/a},
abstract = {Abstract This study investigated the effects of exposure to the ubiquitous
contaminants polychlorinated biphenyls (PCBs) on the fetal adrenal
cortex and on plasma cortisol using the domestic sheep (Ovis aries)
as a model. Pregnant ewes were intendedly subjected to oral treatment
with PCB 153 (98 μg/kg bw/day), PCB 118 (49 μg/kg bw/day) or the
vehicle corn oil from mating until euthanasia on gestation day 134
(±0.25 SE). However, because of accidental cross-contamination occurring
twice causing a mixed exposure scenario in all three groups, the
focus of this paper is to compare three distinct groups of fetuses
with different adipose tissue PCB levels (PCB 153high, PCB 118high
and low, combined groups) rather than comparing animals exposed to
single PCB congeners to those of a control group. When comparing
endocrine and anatomical parameters from fetuses in the PCB 153high
(n = 13) or PCB 118high (n = 14) groups with the low, combined group
(n = 14), there was a significant decrease in fetal body weight (P
< 0.05), plasma cortisol concentration (P < 0.001) and adrenal cortex
thickness (P < 0.001). Furthermore, adrenal weight was decreased
and plasma ACTH was increased only in the PCB 118high group. Expression
of several genes encoding enzymes and receptors related to steroid
hormone synthesis was also affected and mostly down-regulated in
fetuses with high PCB tissue levels. In conclusion, we suggest that
mono-and di-ortho PCBs were able to interfere with growth, adrenal
development and cortisol production in the fetal sheep model. ©
2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.},
doi = {10.1002/tox.20703},
issn = {1522-7278},
keywords = {polychlorinated biphenyls, adrenal gland, cortisol, fetus, endocrine
disruption, steroidogenesis},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/tox.20703}
}
@ARTICLE{Zimmer2011,
author = {Zimmer, Karin E. and Montaño, Mauricio and Olsaker, Ingrid and Dahl,
Ellen and Berg, Vidar and Karlsson, Camilla and Murk, Albertinka
J. and Skaare, Janneche U. and Ropstad, Erik and Verhaegen, Steven},
title = {In vitro steroidogenic effects of mixtures of persistent organic
pollutants (POPs) extracted from burbot (Lota lota) caught in two
Norwegian lakes},
journal = {Science of The Total Environment},
year = {2011},
volume = {409},
pages = {2040--2048},
number = {11},
month = may,
abstract = {This study investigated the effects of two mixtures of persistent
organic pollutants (POPs) on steroidogenesis in the H295R cell line.
The two mixtures were obtained from the livers of burbot (Lota lota)
caught in two Norwegian lakes (Mjøsa and Losna) with different contaminant
profiles. Steroid hormone levels in the cell culture medium and mRNA
levels of 16 genes involved in steroidogenesis were investigated.
The crude Lake Mjøsa extract had to be diluted ten times more than
the Lake Losna extract in order to prevent cytotoxicity. The ten
times diluted Lake Mjøsa mixture had higher levels of DDT and derivates
([summation operator] DDTs, 1.7 times) and brominated flame retardants
([summation operator] BDEs and HBCD, 15-25 times) than the Lake Losna
mixture, which, on the other hand, had higher concentrations of [summation
operator] PCBs (1.5 times higher) and also of HCB, [summation operator] HCH
isomers and [summation operator] chlordane isomers (5-20 times higher).
In the cell culture media, only cortisol levels were increased at
the highest exposure concentration to the Lake Mjøsa mixture, while
both cortisol and estradiol levels were increased following exposure
to the two highest Lake Losna mixture exposure concentrations. Testosterone
levels decreased only at the highest exposure concentration of the
Lake Losna mixture. Multivariate models suggested that [summation
operator] PCBs, and to a lesser extent [summation operator] DDTs,
were responsible for the cortisol responses, while estradiol and
testosterone alterations were best explained by HCB and [summation
operator] PCBs, respectively. Exposure to the mixtures generally
increased mRNA levels, with smaller effects exerted by the Lake Mjøsa
mixture than the Lake Losna mixture. It was concluded that both mixtures
affected steroidogenesis in the H295R cells. Small differences in
mixture composition, rather than the high content of brominated flame
retardants in the Lake Mjøsa mixture, were suggested to be the most
probable reason for the apparent differences in potencies of the
two mixtures.},
issn = {0048-9697},
keywords = {Pollutant, Mixture, H295R, Hormone, Steroidogenesis, PCB, BFR, DDT},
url = {http://www.sciencedirect.com/science/article/pii/S0048969711001148}
}
@ARTICLE{Zimmerman2010,
author = {Zimmerman, Eric I. and Dollins, Claudia M. and Crawford, Melissa
and Grant, Steven and Nana-Sinkam, Serge P. and Richards, Kristy
L. and Hammond, Scott M. and Graves, Lee M.},
title = {Lyn Kinase-Dependent Regulation of miR181 and Myeloid Cell Leukemia-1
Expression: Implications for Drug Resistance in Myelogenous Leukemia},
journal = {Mol. Pharmacol.},
year = {2010},
volume = {78},
pages = {811--817},
number = {5},
month = nov,
abstract = {Imatinib, a BCR-Abl inhibitor, is a successful front-line treatment
for chronic myelogenous leukemia (CML). Despite the success of imatinib,
multiple mechanisms of resistance remain a problem, including overexpression
of Lyn kinase (Lyn) and Bcl-2 family antiapoptotic proteins. Profiling
micro-RNA (miRNA) expression in a model of Lyn-mediated imatinib-resistant
CML (MYL-R) identified approximately 30 miRNAs whose expression differed
>2-fold compared with drug-sensitive MYL cells. In particular, the
expression of the miR181 family (a-d) was significantly reduced ([~]11-
to 25-fold) in MYL-R cells. Incubation of MYL-R cells with a Lyn
inhibitor (dasatinib) or nucleofection with Lyn-targeting short interfering
RNA increased miR181b and miR181d expression. A similar Lyn-dependent
regulation of miR181b and miR181d was observed in imatinib-resistant
K562 CML cells. Sequence analysis of potential targets for miR181
regulation predicted myeloid cell leukemia-1 (Mcl-1), a Bcl-2 family
member whose expression is increased in MYL-R cells and drug-resistant
leukemias. Inhibition of Lyn or rescue of miR181b expression reduced
Mcl-1 expression in the MYL-R cells. To further investigate the mechanism
of Mcl-1 repression by miR181, a luciferase reporter construct incorporating
the Mcl-1 3'-untranslated region was tested. Overexpression of miR181b
reduced luciferase activity, whereas these effects were ablated by
the mutation of the seed region of the miR181 target site. Finally,
stimulation of Lyn expression by 1,25-dihydroxyvitamin D3 treatment
in HL-60 cells, a cell model of acute myelogenous leukemia, decreased
miR181b expression and increased Mcl-1 expression. In summary, our
results suggest that Lyn-dependent regulation of miR181 is a novel
mechanism of regulating Mcl-1 expression and cell survival.},
url = {http://molpharm.aspetjournals.org/cgi/content/abstract/78/5/811}
}
@ARTICLE{Zimmermann2007,
author = {Zimmermann, Bernhard G. And Park, Noh Jin And Wong, David T.},
title = {Genomic Targets in Saliva},
journal = {Annals of the New York Academy of Sciences},
year = {2007},
volume = {1098},
pages = {184--191},
number = {1},
abstract = {Abstract: Saliva, the most accessible and noninvasive biofluid of
our body, harbors a wide spectrum of biological analytes informative
for clinical diagnostic applications. While proteomic constituents
are a logical first choice as salivary diagnostic analytes, genomic
targets have emerged as highly informative and discriminatory. This
awareness, coupled with the ability to harness genomic information
by high-throughput technology platforms such as genome-wide microarrays,
ideally positions salivary genomic targets for exploring the value
of saliva for detection of specific disease states and augmenting
the diagnostic and discriminatory value of the saliva proteome for
clinical applications.Buccal cells and saliva have been used as sources
of genomic DNA for a variety of clinical and forensic applications.
For discovery of disease targets in saliva, the recent realization
that there is a transcriptome in saliva presented an additional target
for oral diagnostics. All healthy subjects evaluated have approximately
3,000 different mRNA molecules in their saliva. Almost 200 of these
salivary mRNAs are present in all subjects. Exploration of the clinical
utility of the salivary transcriptome in oral cancer subjects shows
that four salivary mRNAs (OAZ, SAT, IL8, and IL1b) collectively have
a discriminatory power of 91% sensitivity and specificity for oral
cancer detection. Data are also now in place to validate the presence
of unique diagnostic panels of salivary mRNAs in subjects with Sjögren's
disease.},
issn = {1749-6632},
keywords = {human saliva transcriptome analysis, mRNA biomarkers, noninvasive
disease detection},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1196/annals.1384.002}
}
@ARTICLE{Zimon2006,
author = {Zimon, Alison and Erat, Anna and Wald, Tiffany Von and Bissell, Brad
and Koulova, Anna and Choi, Chu H. and Bachvarov, Dimcho and Reindollar,
Richard H. and Usheva, Anny},
title = {Genes invoked in the ovarian transition to menopause},
journal = {Nucleic Acids Res.},
year = {2006},
volume = {34},
pages = {3279--3287},
number = {11},
month = jun,
abstract = {Menopause and the associated declines in ovarian function are major
health issues for women. Despite the widespread health impact of
this process, the molecular mechanisms underlying the aging-specific
decline in ovarian function are almost completely unknown. To provide
the first gene-protein analysis of the ovarian transition to menopause,
we have established and contrasted RNA gene expression profiles and
protein localization and content patterns in healthy young and perimenopausal
mouse ovaries. We report a clear distinction in specific mRNA and
protein levels that are noted prior to molecular evidence of steroidogenic
failure. In this model, ovarian reproductive aging displays similarities
with chronic inflammation and increased sensitivity to environmental
cues. Overall, our results indicate the presence of mouse climacteric
genes that are likely to be major players in aging-dependent changes
in ovarian function.},
url = {http://nar.oxfordjournals.org/cgi/content/abstract/34/11/3279}
}
@ARTICLE{Zindy2006,
author = {Zindy, Pierre J. and L'Helgoualc'h, Annie and Bonnier, Dominique
and Le Béchec, Antony and Bourd-Boitin, Katia and Zhang, Chang Xian
and Musso, Orlando and Glaise, Denise and Bérangère Troadec, Marie
and Loréal, Olivier and Turlin, Bruno and Léger, Jean and Clément,
Bruno and Théret, Nathalie},
title = {Upregulation of the tumor suppressor gene menin in hepatocellular
carcinomas and its significance in fibrogenesis},
journal = {Hepatology},
year = {2006},
volume = {44},
pages = {1296--1307},
number = {5},
abstract = {Abstract 10.1002/hep.21367.abs The molecular mechanisms underlying
the progression of cirrhosis toward hepatocellular carcinoma were
investigated by a combination of DNA microarray analysis and literature
data mining. By using a microarray screening of suppression subtractive
hybridization cDNA libraries, we first analyzed genes differentially
expressed in tumor and nontumor livers with cirrhosis from 15 patients
with hepatocellular carcinomas. Seventy-four genes were similarly
recovered in tumor (57.8% of differentially expressed genes) and
adjacent nontumor tissues (64% of differentially expressed genes)
compared with histologically normal livers. Gene ontology analyses
revealed that downregulated genes (n = 35) were mostly associated
with hepatic functions. Upregulated genes (n = 39) included both
known genes associated with extracellular matrix remodeling, cell
communication, metabolism, and post-transcriptional regulation gene
(e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple
endocrine neoplasia type 1; MEN1). MEN1 was further identified as
an important node of a regulatory network graph that integrated array
data with array-independent literature mining. Upregulation of MEN1
in tumor was confirmed in an independent set of samples and associated
with tumor size (P = .016). In the underlying liver with cirrhosis,
increased steady-state MEN1 mRNA levels were correlated with those
of collagen α2(I) mRNA (P < .01). In addition, MEN1 expression was
associated with hepatic stellate cell activation during fibrogenesis
and involved in transforming growth factor beta (TGF-β)–dependent
collagen α2(I) regulation. In conclusion, menin is a key regulator
of gene networks that are activated in fibrogenesis associated with
hepatocellular carcinoma through the modulation of TGF-β response.
(HEPATOLOGY 2006;44:1296–1307.)},
issn = {1527-3350},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/hep.21367}
}
@ARTICLE{Ziober2006,
author = {Ziober, Amy F. and Patel, Kirtesh R. and Alawi, Faizan and Gimotty,
Phyllis and Weber, Randall S. and Feldman, Michael M. and Chalian,
Ara A. and Weinstein, Gregory S. and Hunt, Jennifer and Ziober, Barry
L.},
title = {Identification of a Gene Signature for Rapid Screening of Oral Squamous
Cell Carcinoma},
journal = {Clin. Cancer Res.},
year = {2006},
volume = {12},
pages = {5960--5971},
number = {20},
month = oct,
abstract = {Purpose: Oral cancer is a major health problem worldwide and in the
U.S. The 5-year survival rate for oral cancer has not improved significantly
over the past 20 years and remains at [~]50%. Patients diagnosed
at an early stage of the disease typically have an 80% chance for
cure and functional outcome, however, most patients are identified
when the cancer is advanced. Thus, a convenient and an accurate way
to detect oral cancer early will decrease patient morbidity and mortality.
The ability to noninvasively monitor oral cancer onset, progression,
and treatment outcomes requires two prerequisites: identification
of specific biomarkers for oral cancers as well as noninvasive access
to and monitoring of these biomarkers that could be conducted at
the point of care (i.e., practitioner's or dentist's office) by minimally
trained personnel. Experimental Design: Here, we show that DNA microarray
gene expression profiling of matched tumor and normal specimens can
identify distinct anatomic site expression patterns and a highly
significant gene signature distinguishing normal from oral squamous
cell carcinoma (OSCC) tissue. Results: Using a supervised learning
algorithm, we generated a 25-gene signature for OSCC that can classify
normal and OSCC specimens. This 25-gene molecular predictor was 96%
accurate on cross-validation, averaging 87% accuracy using three
independent validation test sets and failing to predict non-oral
tumors. Conclusion: Identification and validation of this tissue-specific
25-gene molecular predictor in this report is our first step towards
developing a new, noninvasive, microfluidic-based diagnostic technology
for mass screening, diagnosis, and treatment of pre-OSCC and OSCC.},
url = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/20/5960}
}
@ARTICLE{Zivraj2010,
author = {Zivraj, Krishna H. and Tung, Yi Chun Loraine and Piper, Michael and
Gumy, Laura and Fawcett, James W. and Yeo, Giles S. H. and Holt,
Christine E.},
title = {Subcellular Profiling Reveals Distinct and Developmentally Regulated
Repertoire of Growth Cone mRNAs},
journal = {J. Neurosci.},
year = {2010},
volume = {30},
pages = {15464--15478},
number = {46},
month = nov,
abstract = {Cue-directed axon guidance depends partly on local translation in
growth cones. Many mRNA transcripts are known to reside in developing
axons, yet little is known about their subcellular distribution or,
specifically, which transcripts are in growth cones. Here laser capture
microdissection (LCM) was used to isolate the growth cones of retinal
ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus,
coupled with unbiased genomewide microarray profiling. An unexpectedly
large pool of mRNAs defined predominant pathways in protein synthesis,
oxidative phosphorylation, cancer, neurological disease, and signaling.
Comparative profiling of "young" (pathfinding) versus "old" (target-arriving)
Xenopus growth cones revealed that the number and complexity of transcripts
increases dramatically with age. Many presynaptic protein mRNAs are
present exclusively in old growth cones, suggesting that functionally
related sets of mRNAs are targeted to growth cones in a developmentally
regulated way. Remarkably, a subset of mRNAs was significantly enriched
in the growth cone compared with the axon compartment, indicating
that mechanisms exist to localize mRNAs selectively to the growth
cone. Furthermore, some receptor transcripts (e.g., EphB4), present
exclusively in old growth cones, were equally abundant in young and
old cell bodies, indicating that RNA trafficking from the soma is
developmentally regulated. Our findings show that the mRNA repertoire
in growth cones is regulated dynamically with age and suggest that
mRNA localization is tailored to match the functional demands of
the growing axon tip as it transforms into the presynaptic terminal.},
comment = {10.1523/JNEUROSCI.1800-10.2010},
url = {http://www.jneurosci.org/cgi/content/abstract/30/46/15464}
}
@ARTICLE{Znaidi2009,
author = {Znaidi, Sadri and Barker, Katherine S. and Weber, Sandra and Alarco,
Anne-Marie and Liu, Teresa T. and Boucher, Genevieve and Rogers,
P. David and Raymond, Martine},
title = {Identification of the Candida albicans Cap1p Regulon},
journal = {Eukaryot. Cell},
year = {2009},
volume = {8},
pages = {806--820},
number = {6},
month = jun,
abstract = {Cap1p, a transcription factor of the basic region leucine zipper family,
regulates the oxidative stress response (OSR) in Candida albicans.
Alteration of its C-terminal cysteine-rich domain (CRD) results in
Cap1p nuclear retention and transcriptional activation. To better
understand the function of Cap1p in C. albicans, we used genome-wide
location profiling (chromatin immunoprecipitation-on-chip) to identify
its transcriptional targets in vivo. A triple-hemagglutinin (HA3)
epitope was introduced at the C terminus of wild-type Cap1p (Cap1p-HA3)
or hyperactive Cap1p with an altered CRD (Cap1p-CSE-HA3). Location
profiling using whole-genome oligonucleotide tiling microarrays identified
89 targets bound by Cap1p-HA3 or Cap1p-CSE-HA3 (the binding ratio
was at least twofold; P [≤] 0.01). Strikingly, Cap1p binding was
detected not only at the promoter region of its target genes but
also at their 3' ends and within their open reading frames, suggesting
that Cap1p may associate with the transcriptional or chromatin remodeling
machinery to exert its activity. Overrepresented functional groups
of the Cap1p targets (P [≤] 0.02) included 11 genes involved in
the OSR (CAP1, GLR1, TRX1, SOD1, CAT1, and others), 13 genes involved
in response to drugs (PDR16, MDR1, FLU1, YCF1, FCR1, and others),
4 genes involved in phospholipid transport (PDR16, GIT1, RTA2, and
orf19.932), and 3 genes involved in the regulation of nitrogen utilization
(GST3, orf19.2693, and orf19.3121), suggesting that Cap1p has other
cellular functions in addition to the OSR. Bioinformatic analyses
of the bound sequences suggest that Cap1p recognizes the DNA motif
5'-MTKASTMA. Finally, transcriptome analyses showed that increased
expression generally accompanies Cap1p binding at its targets, indicating
that Cap1p functions as a transcriptional activator.},
url = {http://ec.asm.org/cgi/content/abstract/8/6/806}
}
@ARTICLE{Zocco2010,
author = {Zocco, M.A. and Lupascu, A. and Riccardi, L. and Piscaglia, A.C.
and Siciliani, L. and Novi, M. and Lauritano, E.C. and Tortora, A.
and Gigante, G. and Santoro, M. and Rinninella, E. and Ainora, M.E.
and Ponziani, F. and Pompili, M. and Rapaccini, G.L. and Gasbarrini,
A.},
title = {603 dynamic contrast enhanced ultrasound in monitoring hcc patients
treated with sorafenib: preliminary results},
journal = {Journal of Hepatology},
year = {2010},
volume = {52},
pages = {S237--S238},
number = {Supplement 1},
month = apr,
booktitle = {Abstracts of the International Liver Congress(TM) 2010 - the 45th
annual meeting of the European Association for the Study of the Liver
(EASL)},
issn = {0168-8278},
url = {http://www.sciencedirect.com/science/article/B6W7C-4YV90TF-RK/2/8cba868b43f07eb751889694dcf718ae}
}
@ARTICLE{Zornetzer2010,
author = {Zornetzer, Gregory A. and Frieman, Matthew B. and Rosenzweig, Elizabeth
and Korth, Marcus J. and Page, Carly and Baric, Ralph S. and Katze,
Michael G.},
title = {Transcriptomic Analysis Reveals a Mechanism for a Prefibrotic Phenotype
in STAT1 Knockout Mice during Severe Acute Respiratory Syndrome Coronavirus
Infection},
journal = {J. Virol.},
year = {2010},
volume = {84},
pages = {11297--11309},
number = {21},
month = nov,
abstract = {Severe acute respiratory syndrome coronavirus (SARS-CoV) infection
can cause the development of severe end-stage lung disease characterized
by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis.
The mechanisms by which pulmonary lesions and fibrosis are generated
during SARS-CoV infection are not known. Using high-throughput mRNA
profiling, we examined the transcriptional response of wild-type
(WT), type I interferon receptor knockout (IFNAR1-/-), and STAT1
knockout (STAT1-/-) mice infected with a recombinant mouse-adapted
SARS-CoV (rMA15) to better understand the contribution of specific
gene expression changes to disease progression. Despite a deletion
of the type I interferon receptor, strong expression of interferon-stimulated
genes was observed in the lungs of IFNAR1-/- mice, contributing to
clearance of the virus. In contrast, STAT1-/- mice exhibited a defect
in the expression of interferon-stimulated genes and were unable
to clear the infection, resulting in a lethal outcome. STAT1-/- mice
exhibited dysregulation of T-cell and macrophage differentiation,
leading to a TH2-biased immune response and the development of alternatively
activated macrophages that mediate a profibrotic environment within
the lung. We propose that a combination of impaired viral clearance
and T-cell/macrophage dysregulation causes the formation of prefibrotic
lesions in the lungs of rMA15-infected STAT1-/- mice.},
url = {http://jvi.asm.org/cgi/content/abstract/84/21/11297}
}
@ARTICLE{ZorroManrique2011,
author = {Zorro Manrique, Soraya and Duque Correa, Maria Adelaida and Hoelzinger,
Dominique B. and Dominguez, Ana Lucia and Mirza, Noweeda and Lin,
Hsi-Hsien and Stein-Streilein, Joan and Gordon, Siamon and Lustgarten,
Joseph},
title = {Foxp3-positive macrophages display immunosuppressive properties and
promote tumor growth},
journal = {J. Exp. Med.},
year = {2011},
volume = {208},
pages = {1485-1499},
number = {7},
abstract = {Regulatory T cells (T reg cells) are characterized by the expression
of the forkhead lineage-specific transcription factor Foxp3, and
their main function is to suppress T cells. While evaluating T reg
cells, we identified a population of Foxp3-positive cells that were
CD11b+F4/80+CD68+, indicating macrophage origin. These cells were
observed in spleen, lymph nodes, bone marrow, thymus, liver, and
other tissues of naive animals. To characterize this subpopulation
of macrophages, we devised a strategy to purify CD11b+F4/80+Foxp3+
macrophages using Foxp3-GFP mice. Analysis of CD11b+F4/80+Foxp3+
macrophage function indicated that these cells inhibited the proliferation
of T cells, whereas Foxp3- macrophages did not. Suppression of T
cell proliferation was mediated through soluble factors. Foxp3- macrophages
acquired Foxp3 expression after activation, which conferred inhibitory
properties that were indistinguishable from natural Foxp3+ macrophages.
The cytokine and transcriptional profiles of Foxp3+ macrophages were
distinct from those of Foxp3- macrophages, indicating that these
cells have different biological functions. Functional in vivo analyses
indicated that CD11b+F4/80+Foxp3+ macrophages are important in tumor
promotion and the induction of T reg cell conversion. For the first
time, these studies demonstrate the existence of a distinct subpopulation
of naturally occurring macrophage regulatory cells in which expression
of Foxp3 correlates with suppressive function.},
doi = {10.1084/jem.20100730},
eprint = {http://jem.rupress.org/cgi/reprint/208/7/1485.pdf},
url = {http://jem.rupress.org/cgi/content/abstract/208/7/1485}
}
@ARTICLE{Zorzi2010,
author = {Zorzi, Penelope and Aplin, Alfred C. and Smith, Kelly D. and Nicosia,
Roberto F.},
title = {Technical Advance: The rat aorta contains resident mononuclear phagocytes
with proliferative capacity and proangiogenic properties},
journal = {J. Leukoc. Biol.},
year = {2010},
volume = {88},
pages = {1051--1059},
number = {5},
month = nov,
abstract = {Angiogenesis in the aortic ring model is preceded by activation of
the immune system and impaired by ablation of adventitial macrophages.
Treatment of aortic cultures with M-CSF induced extensive periaortic
outgrowth of CD45+ CD68+ mononuclear cells with ultrastructural features
of macrophages and DCs. Periaortic lysis of collagen caused many
CD45+ CD68+ cells to attach to the bottom of the culture dish. Lifting
the collagen gels left behind patches of CD45+ CD68+ cells, which
focally organized into branching cords. These cells also expressed
CD14, CD169, F4/80, and {alpha}-SMA but not CD31, vWF, desmin, or
CD163. DNA synthesis studies showed that M-CSF-stimulated cells were
actively proliferating. Aortic patch cells showed phagocytic properties
and responded to IL-4 and GM-CSF by expressing MHC II, differentiating
into DCs, and forming multinucleated giant cells. They also stimulated
angiogenesis and VEGF production in aortic ring cultures. This study
demonstrates that the rat aorta contains a distinct subset of immature
immunocytes capable of proliferating, differentiating into macrophages
and DCs, and stimulating angiogenesis. Isolation of these cells in
patches from M-CSF-stimulated aortic rings provides a reproducible
system to study the biology and angiogenic role of the resident immune
system of the aortic wall.},
url = {http://www.jleukbio.org/cgi/content/abstract/88/5/1051}
}
@ARTICLE{Zou2005,
author = {Zou, Changping And Ramakumar, Sanjay And Qian, Lixin And Zou, Changchun
And Zang, Rongyu And Wang, Jian And Grossman, H. Barton And Lotan,
Reuben And Liebert, Monica},
title = {Effect of retinoic acid and interferon [alpha]-2a on transitional
cell carcinoma of bladder},
journal = {The Journal of Urology},
year = {2005},
volume = {173},
pages = {247--251},
number = {1},
month = jan,
abstract = {ABSTRACTPurpose Retinoids modulate the growth and differentiation
of normal and malignant epithelial cells in vitro and in vivo. Retinoids
and their analogues have been used in animal models and clinical
trials of chemoprevention and superficial bladder cancer treatment.
Interferons are cytokines that have antiviral, antiproliferative
and immunomodulatory function. They are used in many clinical trials
for the treatment of different cancers. To identify new effective
agents and develop novel approaches for the chemoprevention and treatment
of superficial bladder cancer we investigated the effects of a combination
of retinoids and interferon [alpha]-2a (IFN) on growth and apoptosis
in bladder cancer cell lines.Materials and Methods The 4 bladder
cancer cell lines UM-UC-6, UM-UC-9, UM-UC-10 and UM-UC-13 were treated
with 2 retinoids, namely all-trans-retinoic acid (ATRA) and 9-cis
retinoic acid (9cRA), as well as with IFN or with combinations of
retinoids and IFN. The ability of these agents used alone and in
combination to inhibit growth, induce apoptosis and modulate gene
expression was investigated. The effects of retinoids on an INF related
gene were also examined.Results Most bladder cancer cell lines were
resistant to growth inhibition and apoptosis induction by ATRA and
9cRA, even at a high concentration. The effects of these retinoids
on cell growth and apoptosis were enhanced by IFN. The combination
of ATRA and IFN induced retinoic acid receptor [beta], and signal
transducer and activator of transcription 1 expression in 3 bladder
cancer cell lines, as detected by reverse transcriptase-polymerase
chain reaction and Western blot analysis. Retinoids increased IFN-related
gene expression detected by microarray analysis and real-time reverse
transcriptase-polymerase chain reaction.Conclusions The results demonstrate
that IFN acts synergistically with ATRA and 9cRA in the growth and
apoptosis of bladder cancer cells in vitro and suggest that this
combination has a potential for the treatment of transitional cell
carcinoma of the bladder.},
issn = {0022-5347},
keywords = {bladder, carcinoma, transitional cell, retinoids, interferons, apoptosis},
url = {http://www.sciencedirect.com/science/article/B7XMT-4H2P448-2V/2/f9b647b894cfe6d6c06d0ffdb59d20ea}
}
@ARTICLE{Zoueva2004,
author = {Zoueva, Olga P. and Rodgers, Griffin P.},
title = {Inhibition of [beta] protein 1 expression enhances [beta]-globin
promoter activity and [beta]-globin mRNA levels in the human erythroleukemia
(K562) cell line},
journal = {Experimental Hematology},
year = {2004},
volume = {32},
pages = {700--708},
number = {8},
month = aug,
abstract = {Objective In this paper, we report new observations related to the
mechanism of the negative regulation of the important adult [beta]-globin
gene in the erythroid cells at the embryonic-fetal stage of their
development. We focused on the role of the silencer II region located
upstream of the [beta]-globin gene, which along with its cognate
binding protein BP1, negatively regulates [beta]-globin transcription.Materials
and methods We prepared plasmid constructs containing the wild-type
silencer II sequence, a mutated silencer II sequence, or a mutated
control sequence in the [beta]-globin promoter 690-bp insert, which
in turn was linked to an enhanced green fluorescent protein (EGFP)
reporter gene. A human erythroleukemia cell line (K562) with embryonic-fetal
phenotype was transfected with these EGFP constructs.Results Flow
cytometry and fluorescence digital imaging showed about threefold
increase in the [beta]-globin promoter activity of the mutated silencer
II construct. Introduction of a small interfering RNA (siRNA) complementary
to BP1 into the cells caused a 75% decrease in BP1 expression and
a simultaneous ~40% elevation of [beta]-globin promoter activity
as well as an increase in [beta]-globin mRNA levels, as compared
with controls. We detected no changes in the mRNA levels of positive
regulators of hemoglobin transcription such as EKLF and GATA-1.Conclusion
Our results support the involvement of BP1 in the mechanism of the
negative regulation of [beta]-globin transcription. A better understanding
of this mechanism may lay the groundwork for novel gene therapy approaches
to inhibit the expression of abnormal structural variants of adult
[beta] globin, such as sickle hemoglobin.},
issn = {0301-472X},
url = {http://www.sciencedirect.com/science/article/B6VP8-4D2C498-8/2/80a875d3a8eec2d121090a974df348e5}
}
@ARTICLE{Zraly2006,
author = {Zraly, Claudia B. and Middleton, Frank A. and Dingwall, Andrew K.},
title = {Hormone-response Genes Are Direct in Vivo Regulatory Targets of Brahma
(SWI/SNF) Complex Function},
journal = {J. Biol. Chem.},
year = {2006},
volume = {281},
pages = {35305--35315},
number = {46},
month = nov,
abstract = {Metazoan SWI/SNF chromatin remodeling complexes exhibit ATP-dependent
activation and repression of target genes. The Drosophila Brahma
(SWI/SNF) complex subunits BRM and SNR1 are highly conserved with
direct counterparts in yeast (SWI2/SNF2 and SNF5) and mammals (BRG1/hBRM
and INI1/hSNF5). BRM encodes the catalytic ATPase required for chromatin
remodeling and SNR1 is a regulatory subunit. Importantly, SNR1 mediates
ATP-independent repression functions of the complex in cooperation
with histone deacetylases and direct contacts with gene-specific
repressors. SNR1 and INI1, as components of their respective SWI/SNF
complexes, are important for developmental growth control and patterning,
with direct function as a tumor suppressor. To identify direct regulatory
targets of the Brm complex, we performed oligonucleotide-based transcriptome
microarray analyses using RNA isolated from mutant fly strains harboring
dominant-negative alleles of snr1 and brm. Steady-state RNA isolated
from early pupae was examined, as this developmental stage critically
requires Brm complex function. We found the hormone-responsive Ecdysone-induced
genes (Eig) were strongly misregulated and that the Brm complex is
directly associated with the promoter regions of these genes in vivo.
Our results reveal that the Brm complex assists in coordinating hormone-dependent
transcription regulation of the Eig genes.},
url = {http://www.jbc.org/cgi/content/abstract/281/46/35305}
}
@ARTICLE{Zrioual2009,
author = {Zrioual, Saloua and Ecochard, Rene and Tournadre, Anne and Lenief,
Vanina and Cazalis, Marie-Angelique and Miossec, Pierre},
title = {Genome-Wide Comparison between IL-17A- and IL-17F-Induced Effects
in Human Rheumatoid Arthritis Synoviocytes},
journal = {J. Immunol.},
year = {2009},
volume = {182},
pages = {3112--3120},
number = {5},
month = mar,
abstract = {IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; however,
the contribution of IL-17F remains to be clarified. Using microarrays
and gene-specific expression assays, we compared the regulatory effects
of IL-17A and IL-17F alone or in combination with TNF-{alpha} on
RA synoviocytes. IL-17A and IL-17F expression was studied in osteoarthritis
and RA synovium by immunohistochemistry. The comparison between the
IL-17A and IL-17F stimulatory effect on RA synoviocytes was assessed
at the protein level by ELISA and at the mRNA level by microarrays
and real-time RT-PCR. TNFRII expression was studied by real-time
RT-PCR and immunofluorescence, and neutralizing Ab was used to analyze
its contribution to CCL20 secretion. IL-17A and IL-17F were detected
in plasma cell-like cells from RA but not osteoarthritis synovium.
In microarrays, IL-17A and IL-17F alone had similar regulatory effects,
IL-17F being quantitatively less active. Both cytokines induced a
similar expression pattern in the presence of TNF-{alpha}. Based
on a cooperation index, 130 and 203 genes were synergistically induced
by IL-17A or IL-17F plus TNF-{alpha}, respectively. Among these,
the new target genes CXCR4, LPL, and IL-32 were validated by real-time
RT-PCR. IL-17A and IL-17F up-regulated TNFRII expression, but had
no effects on TNFRI, IL-17RA or IL-17RC. TNFRII blockade inhibited
the synergistic induction of CCL20 by IL-17A or IL-17F and TNF-{alpha}.
IL-17A and IL-17F are both expressed in RA synovium. In the presence
of TNF-{alpha}, they induced a similar expression pattern in RA synoviocytes.
Accordingly, IL-17F appears as a target in Th17-mediated diseases
such as RA.},
url = {http://www.jimmunol.org/cgi/content/abstract/182/5/3112}
}
@ARTICLE{Zrioual2008,
author = {Zrioual, Saloua and Toh, Myew-Ling and Tournadre, Anne and Zhou,
Yuan and Cazalis, Marie-Angelique and Pachot, Alexandre and Miossec,
Vincent and Miossec, Pierre},
title = {IL-17RA and IL-17RC Receptors Are Essential for IL-17A-Induced ELR+
CXC Chemokine Expression in Synoviocytes and Are Overexpressed in
Rheumatoid Blood},
journal = {J. Immunol.},
year = {2008},
volume = {180},
pages = {655--663},
number = {1},
month = jan,
abstract = {IL-17A is a cytokine secreted by the newly described Th17 cells implicated
in rheumatoid arthritis (RA). Less is known about its receptors in
synoviocytes. IL-17RA and IL-17RC were found to be overexpressed
in RA peripheral whole blood and their expression was detected locally
in RA synovium. In vitro, IL-17A synergized with TNF-{alpha} to induce
IL-6, IL-8, CCL-20, and matrix metalloproteinase-3. Using microarrays,
a specific up-regulation of Glu-Leu-Arg+ CXC chemokines was observed
in IL-17A-treated synoviocytes. Using both posttranslational inhibitions
by silencing interfering RNA and extracellular blockade by specific
inhibitors, we showed that both IL-17RA and IL-17RC are implicated
in IL-17A-induced IL-6 secretion, whereas in the presence of TNF-{alpha},
the inhibition of both receptors was needed to down-regulate IL-17A-induced
IL-6 and CCL-20 secretion. Thus, IL-17A-induced IL-6, IL-8, and CCL20
secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed
in RA patients. IL-17A-induced pathogenic effects may be modulated
by IL-17RA and/or IL-17RC antagonism.},
url = {http://www.jimmunol.org/cgi/content/abstract/180/1/655}
}
@ARTICLE{Zubkova2009,
author = {Zubkova, I. and Choi, Y.H. and Chang, E. and Pirollo, K. and Uren,
T. and Watanabe, H. and Wells, F. and Kachko, A. and Krawczynski,
K. and Major, M.E.},
title = {T-cell vaccines that elicit effective immune responses against HCV
in chimpanzees may create greater immune pressure for viral mutation},
journal = {Vaccine},
year = {2009},
volume = {27},
pages = {2594--2602},
number = {19},
month = apr,
abstract = {A prime/boost vaccine strategy that transfects antigen-presenting
cells using ligand-modified immunoliposomes to efficiently deliver
plasmid DNA, followed by boosting with non-replicating recombinant
adenovirus was used in chimpanzees to generate HCV-specific memory
T-cells. Three chimpanzees (two vaccines, one control) were immunized
with immunoliposomes complexed with DNA expressing NS3-NS5B or complexed
with empty vector. Animals were boosted with adenovirus expressing
NS3-NS5B, or non-recombinant adenovirus (control). Using liposome
delivery we were able to obtain specific HCV responses following
DNA priming in the chimpanzees. This data and mouse immunization
studies confirm this as a more efficient delivery system than direct
intramuscular inoculations with naked DNA. Subsequent to the adenovirus
boost significant increases in peripheral HCV-specific T-cell responses
and intrahepatic IFN-[gamma] and CD3[var epsilon] mRNA were also
observed in the two vaccinated animals. Following challenge (100
CID50) both vaccinated animals showed immediate and significant control
of viral replication (peak titers 3.7 × 104 and 9 × 103 IU/mL at
weeks 1 and 2), which coincided with increases in HCV-specific T-cell
responses. Viral kinetics in the control animal were comparable to
historical controls with exponential increases in titer during the
first several weeks. One vaccinated animal developed a low-level
persistent infection (2 × 103 IU/mL) which correlated with a decrease
in HCV-specific T-cell responses. Circulating virus isolated from
both vaccinated animals showed ~2-fold greater nonsynonymous mutation
rates compared to controls and the nonsynonymous/synonymous mutation
rate ratio was indicative of positive selection. These data suggest
that although T-cell vaccines can induce immune responses capable
of controlling HCV, they also induce high levels of immune pressure
for the potential selection of escape mutants.},
issn = {0264-410X},
keywords = {Hepatitis C virus, T-cell, Immune escape, Chimpanzee},
url = {http://www.sciencedirect.com/science/article/B6TD4-4VP66BN-3/2/8b68669fbfddf05a52ad328fe279255b}
}
@ARTICLE{Zucchi2011,
author = {Sara Zucchi and Daniela M. Oggier and Karl Fent},
title = {Global gene expression profile induced by the UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate
(EHMC) in zebrafish (Danio rerio)},
journal = {Environmental Pollution},
year = {2011},
volume = {159},
pages = {3086 - 3096},
number = {10},
note = {Nitrogen Deposition, Critical Loads and Biodiversity},
abstract = {Residues of the UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC)
are ubiquitously found in aquatic biota but potential adverse effects
in fish are fairly unknown. To identify molecular effects and modes
of action of EHMC we applied a gene expression profiling in zebrafish
using whole genome microarrays. Transcriptome analysis and validation
of targeted genes were performed after 14 days of exposure of male
zebrafish. Concentrations of 2.2 μg/L and 890 μg/L EHMC lead
to alteration of 1096 and 1137 transcripts, respectively, belonging
to many pathways. Genes involved in lipid metabolism and estrogenic
pathway (vtg1), lipid biosynthesis (ptgds), vitamin A metabolic process
(rbp2a), DNA damage and apoptosis (gadd45b), and regulation of cell
growth (igfbp1a) were investigated by qRT-PCR analysis in whole body,
liver, brain and testis. The analysis showed tissue-specific gene
profiles and revealed that EHMC slightly affects the transcription
of genes involved in hormonal pathways including vtg1, esr1, esr2b,
ar, cyp19b and hsd17β3.},
doi = {10.1016/j.envpol.2011.04.013},
issn = {0269-7491},
keywords = {UV-filter},
url = {http://www.sciencedirect.com/science/article/pii/S0269749111002193}
}
@ARTICLE{Zucchini2008,
author = {Zucchini, Nicolas and Bessou, Gilles and Robbins, Scott H. and Chasson,
Lionel and Raper, Anna and Crocker, Paul R. and Dalod, Marc},
title = {Individual plasmacytoid dendritic cells are major contributors to
the production of multiple innate cytokines in an organ-specific
manner during viral infection},
journal = {Int. Immunol.},
year = {2008},
volume = {20},
pages = {45--56},
number = {1},
month = jan,
abstract = {Plasmacytoid dendritic cells (pDCs) are an important source of IFN-{alpha}/{beta}
in response to a variety of viruses in vivo, including murine cytomegalovirus
(MCMV). However, the respective contributions of various infected
organs, and within these of pDCs, conventional dendritic cells and
other cells, to the systemic production of IFN-{alpha}/{beta} or
other innate cytokines during viral infections in vivo is largely
unknown. Whether a specialization of pDC subsets in the production
of different patterns of innate cytokines exists in vivo in response
to a viral infection has not been investigated. Here, by analyzing
for the first time directly ex vivo, at the single-cell level, the
simultaneous production of up to three cytokines in pDCs isolated
from MCMV-infected mice, we show that (i) pDCs are the quasi-exclusive
source of IFN-{alpha}/{beta}, IL-12 and tumor necrosis factor (TNF)-{alpha},
early during MCMV infection, in two immunocompetent mouse lines and
with two viral strains, (ii) pDC activation for IFN-{alpha}/{beta}
production is organ specific and (iii) a significant proportion of
pDCs simultaneously produce IFN-{alpha}/{beta}, TNF-{alpha} and IL-12,
although TNF-{alpha} and IFN-{alpha}/{beta} appear more often co-expressed
with one another than each of them with IL-12. Altogether, these
results show a broad and non-redundant role of pDCs in early innate
detection of, and defense against, viral infection. The data also
show differences in the responsiveness of pDCs from different tissues
and suggest distinct molecular requirements for pDC production of
various cytokines. These observations must be taken into account
when designing new antiviral vaccination strategies aimed at harnessing
pDC responses.},
url = {http://intimm.oxfordjournals.org/cgi/content/abstract/20/1/45}
}
@ARTICLE{Zuccolo2011,
author = {Zuccolo, Andrea and Bowers, John and Estill, James and Xiong, Zhiyong
and Luo, Meizhong and Sebastian, Aswathy and Goicoechea, Jose and
Collura, Kristi and Yu, Yeisoo and Jiao, Yuannian and Duarte, Jill
and Tang, Haibao and Ayyampalayam, Saravanaraj and Rounsley, Steve
and Kudrna, Dave and Paterson, Andrew and Pires, J and Chanderbali,
Andre and Soltis, Douglas and Chamala, Srikar and Barbazuk, Brad
and Soltis, Pamela and Albert, Victor and Ma, Hong and Mandoli, Dina
and Banks, Jody and Carlson, John and Tomkins, Jeffrey and dePamphilis,
Claude and Wing, Rod and Leebens-Mack, Jim},
title = {A physical map for the Amborella trichopoda genome sheds light on
the evolution of angiosperm genome structure},
journal = {Genome Biology},
year = {2011},
volume = {12},
pages = {R48},
number = {5},
abstract = {BACKGROUND:Recent phylogenetic analyses have identified Amborella
trichopoda, an understory tree species endemic to the forests of
New Caledonia, as sister to a clade including all other known flowering
plant species. The Amborella genome is a unique reference for understanding
the evolution of angiosperm genomes because it can serve as an outgroup
to root comparative analyses. A physical map, BAC end sequences and
sample shotgun sequences provide a first view of the 870 Mbp Amborella
genome.RESULTS:Analysis of Amborella BAC ends sequenced from each
contig suggests that the density of long terminal repeat retrotransposons
is negatively correlated with that of protein coding genes. Syntenic,
presumably ancestral, gene blocks were identified in comparisons
of the Amborella BAC contigs and the sequenced Arabidopsis thaliana,
Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony
mapping of the loss of synteny corroborates previous analyses suggesting
that the rate of structural change has been more rapid on lineages
leading to Arabidopsis and Oryza compared with lineages leading to
Populus and Vitis. The gamma paleohexiploidy event identified in
the Arabidopsis, Populus and Vitis genomes is shown to have occurred
after the divergence of all other known angiosperms from the lineage
leading to Amborella.CONCLUSIONS:When placed in the context of a
physical map, BAC end sequences representing just 5.4% of the Amborella
genome have facilitated reconstruction of gene blocks that existed
in the last common ancestor of all flowering plants. The Amborella
genome is an invaluable reference for inferences concerning the ancestral
angiosperm and subsequent genome evolution.},
doi = {10.1186/gb-2011-12-5-r48},
issn = {1465-6906},
pubmedid = {21619600},
url = {http://genomebiology.com/2011/12/5/R48}
}
@ARTICLE{Zuercher2010,
author = {Zuercher, Jurian and Neidhardt, John and Magyar, Istvan and Labs,
Stephan and Moore, Anthony T. and Tanner, Felix C. and Waseem, Naushin
and Schorderet, Daniel F. and Munier, Francis L. and Bhattacharya,
Shomi and Berger, Wolfgang and Kloeckener-Gruissem, Barbara},
title = {Alterations of the 5'Untranslated Region of SLC16A12 Lead to Age-Related
Cataract},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2010},
volume = {51},
pages = {3354--3361},
number = {7},
month = jul,
abstract = {Purpose.Knowledge of genetic factors predisposing to age-related cataract
is very limited. The aim of this study was to identify DNA sequences
that either lead to or predispose for this disease. Methods.The candidate
gene SLC16A12, which encodes a solute carrier of the monocarboxylate
transporter family, was sequenced in 484 patients with cataract (134
with juvenile cataract, 350 with age-related cataract) and 190 control
subjects. Expression studies included luciferase reporter assay and
RT-PCR experiments. Results.One patient with age-related cataract
showed a novel heterozygous mutation (c.-17A>G) in the 5'untranslated
region (5'UTR). This mutation is in cis with the minor G-allele of
the single nucleotide polymorphism (SNP) rs3740030 (c.-42T/G), also
within the 5'UTR. Using a luciferase reporter assay system, a construct
with the patient's haplotype caused a significant upregulation of
luciferase activity. In comparison, the SNP G-allele alone promoted
less activity, but that amount was still significantly higher than
the amount of the common T-allele. Analysis of SLC16A12 transcripts
in surrogate tissue demonstrated striking allele-specific differences
causing 5'UTR heterogeneity with respect to sequence and quantity.
These differences in gene expression were mirrored in an allele-specific
predisposition to age-related cataract, as determined in a Swiss
population (odds ratio approximately 2.2; confidence intervals, 1.23-4.3).
Conclusions.The monocarboxylate transporter SLC16A12 may contribute
to age-related cataract. Sequences within the 5'UTR modulate translational
efficiency with pathogenic consequences.},
url = {http://www.iovs.org/cgi/content/abstract/51/7/3354}
}
@ARTICLE{Zuerner2007,
author = {Zuerner, Richard L. and Heidari, Mohammad and Elliott, Margaret K.
and Alt, David P. and Neill, John D.},
title = {Papillomatous digital dermatitis spirochetes suppress the bovine
macrophage innate immune response},
journal = {Veterinary Microbiology},
year = {2007},
volume = {125},
pages = {256--264},
number = {3-4},
month = dec,
abstract = {Papillomatous digital dermatitis (PDD) is a polymicrobial infection
in soft tissue adjacent to the hoof and is the leading cause of lameness
in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are
a constant feature of PDD lesions and are localized deep in infected
tissue. Host-cell response mechanisms to TPL spirochetes are poorly
understood. To assess how bovine macrophages respond to cellular
constituents of TPL spirochetes, changes in transcription were analyzed
using serial analysis of gene expression (SAGE) and real time RT-PCR.
This analysis revealed that some proinflammatory cytokines (e.g.
GCP-2 and IL-8) are induced in treated macrophages, while receptors
and their accessory proteins for IL-1, IL-6 and IL-11 are either
down regulated or unchanged. Two genes encoding proteins having negative
effects on NF[kappa]B, I[kappa]B and SIVA-1, are significantly induced
in stimulated cells. Several genes associated with the cytoskeleton
and antigen presentation are down regulated after exposure to sonicated
TPL spirochetes, as are genes associated with wound repair. Combined,
these data suggest that the innate immune and wound repair functions
of bovine macrophages exposed to TPL cellular constituents are impaired
thereby enabling bacteria to resist clearance and induce lesion formation.
Use of this in vitro bovine macrophage model should be useful in
elucidating host-spirochete interactions and facilitate identification
of potential virulence traits.},
issn = {0378-1135},
keywords = {Treponema, Papillomatous digital dermatitis, SAGE, Real time RT-PCR},
url = {http://www.sciencedirect.com/science/article/B6TD6-4NYJ0S3-8/2/201dd7ee2bc4db681f3bc1ee9ed7cb99}
}
@ARTICLE{Zuna2010,
author = {Zuna, Jan and Zaliova, Marketa and Muzikova, Katerina and Meyer,
Claus and Lizcova, Libuse and Zemanova, Zuzana and Brezinova, Jana
and Votava, Felix and Marschalek, Rolf and Stary, Jan and Trka, Jan},
title = {Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and
prenatal origin},
journal = {Genes Chromosom. Cancer},
year = {2010},
volume = {49},
pages = {873--884},
number = {10},
abstract = {Abstract 10.1002/gcc.20796.abs The ETV6/ABL1 (TEL/ABL) fusion gene
is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1-positive
hematological malignancy have been published, diagnosed with chronic
myeloid leukemia, other types of chronic myeloproliferative neoplasm,
acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This
study reports three new cases (aged 8 months, 5 years, and 33 years)
of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed
ALL patients (335 children and 57 adults). A thorough review of the
literature and an analysis of all published data, including the three
new cases, suggest poor prognosis of ETV6/ABL1-positive acute leukemias.
The course of the disease in the two pediatric patients is characterized
by minimal residual disease monitoring, using quantification of both
the ETV6/ABL1 transcript and immunoreceptor gene rearrangements.
Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1-positive
disease. Studies of neonatal blood spots demonstrated that, in the
child diagnosed at five years, the ETV6/ABL1 fusion initiating the
ALL originated prenatally. © 2010 Wiley-Liss, Inc.},
issn = {1098-2264},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
url = {http://dx.doi.org/10.1002/gcc.20796}
}
@ARTICLE{Zuntini2010,
author = {Zuntini, M and Salvatore, M and Pedrini, E and Parra, A and Sgariglia,
F and Magrelli, A and Taruscio, D and Sangiorgi, L},
title = {MicroRNA profiling of multiple osteochondromas: identification of
disease-specific and normal cartilage signatures},
journal = {Clinical Genetics},
year = {2010},
volume = {78},
pages = {507--516},
number = {6},
abstract = {Zuntini M, Salvatore M, Pedrini E, Parra A, Sgariglia F, Magrelli
A, Taruscio D, Sangiorgi L. MicroRNA profiling of Multiple Osteochondromas:
identification of disease-specific and normal cartilage signatures.
Multiple osteochondroma (MO) is a rare skeletal disease characterized
by the formation of multiple benign cartilage-capped bone tumors;
in 1–5% of patients, a malignant transformation into peripheral
chondrosarcoma may occur. This disorder is characterized by a large
spectrum of germline mutations scattered along EXT1/EXT2 genes, the
presence of a significant percentage of patients without alterations
in EXT genes, and a large phenotypic variability. The molecular basis
of MO genetic and clinical heterogeneity, including the causes underlying
malignant transformation, is currently unknown. This leads to the
lack of appropriate diagnostic/prognostic markers as well as of therapeutic
options. Recently, specific microRNAs (miRNAs) were reported to be
involved in chondrogenesis and inflammatory cartilage diseases. We
therefore hypothesized a role for microRNAs in cartilaginous tumors
and investigated microRNA expression in osteochondroma and normal
cartilage tissues to evaluate whether they could affect osteochondromas
onset and/or clinical manifestations. Our results indicate that miRNAs
differentially expressed in MO samples may hamper the molecular signaling
responsible for normal differentiation of chondrocytes, contributing
to pathogenesis and clinical outcome. Although further studies are
needed to validate our observations and to identify targets of miRNAs,
this is the first study reporting on miRNA expression in growth plate
and its comparison with pathological conditions.},
issn = {1399-0004},
keywords = {articular cartilage, endochondral ossification signaling pathways,
growth plate cartilage, microRNA profiling, Multiple Osteochondromas},
publisher = {Blackwell Publishing Ltd},
url = {http://dx.doi.org/10.1111/j.1399-0004.2010.01490.x}
}
@ARTICLE{Zuo2008,
author = {Zuo, Ying and Zhuang, Debbie Z. and Han, Rong and Isaac, Giorgis
and Tobin, Jennifer J. and McKee, Mary and Welti, Ruth and Brissette,
Janice L. and Fitzgerald, Michael L. and Freeman, Mason W.},
title = {ABCA12 Maintains the Epidermal Lipid Permeability Barrier by Facilitating
Formation of Ceramide Linoleic Esters},
journal = {J. Biol. Chem.},
year = {2008},
volume = {283},
pages = {36624--36635},
number = {52},
month = dec,
abstract = {Harlequin ichthyosis is a congenital scaling syndrome of the skin
in which affected infants have epidermal hyperkeratosis and a defective
permeability barrier. Mutations in the gene encoding a member of
the ABCA transporter family, ABCA12, have been linked to harlequin
ichthyosis, but the molecular function of the protein is unknown.
To investigate the activity of ABCA12, we generated Abca12 null mice
and analyzed the impact on skin function and lipid content. Abca12-/-
mice are born with a thickened epidermis and die shortly after birth,
as water rapidly evaporates from their skin. In vivo skin proliferation
measurements suggest a lack of desquamation of the skin cells, rather
than enhanced proliferation of basal layer keratinocytes, accounts
for the 5-fold thickening of the Abca12-/- stratum corneum. Electron
microscopy revealed a loss of the lamellar permeability barrier in
Abca12-/- skin. This was associated with a profound reduction in
skin linoleic esters of long-chain {omega}-hydroxyceramides and a
corresponding increase in their glucosyl ceramide precursors. Because
{omega}-hydroxyceramides are required for the barrier function of
the skin, these results establish that ABCA12 activity is required
for the generation of long-chain ceramide esters that are essential
for the development of normal skin structure and function.},
url = {http://www.jbc.org/cgi/content/abstract/283/52/36624}
}
@ARTICLE{Zusso2008,
author = {Zusso, Morena and Debetto, Patrizia and Guidolin, Diego and Barbierato,
Massimo and Manev, Hari and Giusti, Pietro},
title = {Fluoxetine-induced proliferation and differentiation of neural progenitor
cells isolated from rat postnatal cerebellum},
journal = {Biochemical Pharmacology},
year = {2008},
volume = {76},
pages = {391--403},
number = {3},
month = aug,
issn = {0006-2952},
keywords = {Postnatal cerebellar neural progenitors, 5HT1A, cAMP-response element-binding
(CREB) protein, Extracellular signal-regulated protein kinase (ERK1/2),
Selective serotonin-reuptake inhibitors (SSRIs)},
url = {http://www.sciencedirect.com/science/article/B6T4P-4SK62SX-1/2/6f21bdef833a54005c964e8a71bb84d6}
}
@ARTICLE{Zutphen2010,
author = {van Zutphen, Tim and Baerends, Richard and Susanna, Kim and de Jong,
Anne and Kuipers, Oscar and Veenhuis, Marten and van der Klei, Ida},
title = {Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis},
journal = {BMC Genomics},
year = {2010},
volume = {11},
pages = {1},
number = {1},
abstract = {BACKGROUND:Methylotrophic yeast species (e.g. Hansenula polymorpha,
Pichia pastoris) can grow on methanol as sole source of carbon and
energy. These organisms are important cell factories for the production
of recombinant proteins, but are also used in fundamental research
as model organisms to study peroxisome biology. During exponential
growth on glucose, cells of H. polymorpha typically contain a single,
small peroxisome that is redundant for growth while on methanol multiple,
enlarged peroxisomes are present. These organelles are crucial to
support growth on methanol, as they contain key enzymes of methanol
metabolism.In this study, changes in the transcriptional profiles
during adaptation of H. polymorpha cells from glucose- to methanol-containing
media were investigated using DNA-microarray analyses.RESULTS:Two
hours after the shift of cells from glucose to methanol nearly 20%
(1184 genes) of the approximately 6000 annotated H. polymorpha genes
were significantly upregulated with at least a two-fold differential
expression. Highest upregulation (> 300-fold) was observed for the
genes encoding the transcription factor Mpp1 and formate dehydrogenase,
an enzyme of the methanol dissimilation pathway. Upregulated genes
also included genes encoding other enzymes of methanol metabolism
as well as of peroxisomal ß-oxidation.A moderate increase in transcriptional
levels (up to 4-fold) was observed for several PEX genes, which are
involved in peroxisome biogenesis. Only PEX11 and PEX32 were higher
upregulated. In addition, an increase was observed in expression
of the several ATG genes, which encode proteins involved in autophagy
and autophagy processes. The strongest upregulation was observed
for ATG8 and ATG11.Approximately 20% (1246 genes) of the genes were
downregulated. These included glycolytic genes as well as genes involved
in transcription and translation.CONCLUSION:Transcriptional profiling
of H. polymorpha cells shifted from glucose to methanol showed the
expected downregulation of glycolytic genes together with upregulation
of the methanol utilisation pathway. This serves as a confirmation
and validation of the array data obtained. Consistent with this,
also various PEX genes were upregulated. The strong upregulation
of ATG genes is possibly due to induction of autophagy processes
related to remodeling of the cell architecture required to support
growth on methanol. These processes may also be responsible for the
enhanced peroxisomal ß-oxidation, as autophagy leads to recycling
of membrane lipids. The prominent downregulation of transcription
and translation may be explained by the reduced growth rate on methanol
(td glucose 1 h vs td methanol 4.5 h).},
doi = {10.1186/1471-2164-11-1},
issn = {1471-2164},
pubmedid = {20044946},
url = {http://www.biomedcentral.com/1471-2164/11/1}
}
@ARTICLE{Zvonic2006,
author = {Zvonic, Sanjin and Ptitsyn, Andrey A. and Conrad, Steven A. and Scott,
L. Keith and Floyd, Z. Elizabeth and Kilroy, Gail and Wu, Xiying
and Goh, Brian C. and Mynatt, Randall L. and Gimble, Jeffrey M.},
title = {Characterization of Peripheral Circadian Clocks in Adipose Tissues},
journal = {Diabetes},
year = {2006},
volume = {55},
pages = {962--970},
number = {4},
month = apr,
abstract = {First described in the suprachiasmatic nucleus, circadian clocks have
since been found in several peripheral tissues. Although obesity
has been associated with dysregulated circadian expression profiles
of leptin, adiponectin, and other fat-derived cytokines, there have
been no comprehensive analyses of the circadian clock machinery in
adipose depots. In this study, we show robust and coordinated expression
of circadian oscillator genes (Npas2, Bmal1, Per1-3, and Cry1-2)
and clock-controlled downstream genes (Rev-erb{alpha}, Rev-erb{beta},
Dbp, E4bp4, Stra13, and Id2) in murine brown, inguinal, and epididymal
(BAT, iWAT, and eWAT) adipose tissues. These results correlated with
respective gene expression in liver and the serum markers of circadian
function. Through Affymetrix microarray analysis, we identified 650
genes that shared circadian expression profiles in BAT, iWAT, and
liver. Furthermore, we have demonstrated that temporally restricted
feeding causes a coordinated phase-shift in circadian expression
of the major oscillator genes and their downstream targets in adipose
tissues. The presence of circadian oscillator genes in fat has significant
metabolic implications, and their characterization may have potential
therapeutic relevance with respect to the pathogenesis and treatment
of diseases such as obesity, type 2 diabetes, and the metabolic syndrome.},
url = {http://diabetes.diabetesjournals.org/cgi/content/abstract/55/4/962}
}
@ARTICLE{Zvonic2007,
author = {Zvonic, Sanjin and Ptitsyn, Andrey A and Kilroy, Gail and Wu, Xiying
and Conrad, Steven A and Scott, L Keith and Guilak, Farshid and Pelled,
Gadi and Gazit, Dan and Gimble, Jeffrey M},
title = {Circadian Oscillation of Gene Expression in Murine Calvarial Bone},
journal = {J Bone Miner Res},
year = {2007},
volume = {22},
pages = {357--365},
number = {3},
abstract = {Abstract 10.1359/jbmr.061114.abs The genes encoding the core circadian
transcription factors display an oscillating expression profile in
murine calvarial bone. More than 26% of the calvarial bone transcriptome
exhibits a circadian rhythm, comparable with that observed in brown
and white adipose tissues and liver. Thus, circadian mechanisms may
directly modulate oxidative phosphorylation and multiple metabolic
pathways in bone homeostasis. Introduction: Although circadian rhythms
have been associated historically with central regulatory mechanisms,
there is emerging evidence that the circadian transcriptional apparatus
exists in peripheral tissues. The aim of this study was to determine
the presence and extent of circadian oscillation in the transcriptome
of murine calvarial bone. Materials and Methods: Cohorts of 8-week-old
male AKR/J mice were maintained in a controlled 12-h light:12-h dark
cycle on an ad libitum diet for 2 weeks. Groups of three mice were
killed every 4 h over a 48-h period. The level of gene expression
at successive times-points was determined by quantitative RT-PCR
and Affymetrix microarray. Data were analyzed using multiple statistical
time series algorithms, including Cosinor, Fisher g-test, and the
permutation time test. Results: Both the positive (Bmal1, Npas2)
and negative (Cry1, Cry2, Per1, Per2, Per3) elements of the circadian
transcriptional apparatus and their immediate downstream targets
and mediators (Dbp, Rev-erbα, Rev-erbβ) exhibited oscillatory expression
profiles. Consistent with findings in other tissues, the positive
and negative elements were in antiphase relative to each other. More
than 26% of the genes present on the microarray displayed an oscillatory
profile in calvarial bone, comparable with the levels observed in
brown and white adipose tissues and liver; however, only a subset
of 174 oscillating genes were shared among all four tissues. Conclusions:
Our findings show that the components of the circadian transcriptional
apparatus are represented in calvarial bone and display coordinated
oscillatory behavior. However, these are not the only genes to display
an oscillatory expression profile, which is seen in multiple pathways
involving oxidative phosphorylation and lipid, protein, and carbohydrate
metabolism.},
issn = {1523-4681},
keywords = {bone metabolism, brown adipose, circadian, glucocorticoid receptor,
heat shock protein, liver, oxidative phosphorylation, white adipose},
publisher = {John Wiley and Sons and The American Society for Bone and Mineral
Research (ASBMR)},
url = {http://dx.doi.org/10.1359/jbmr.061114}
}
@ARTICLE{Zwick2003,
author = {Zwick, Melissa and Molliver, Derek C. and Lindsay, Jessica and Fairbanks,
Carolyn A. and Sengoku, Tomoko and Albers, Kathryn M. and Davis,
Brian M.},
title = {Transgenic mice possessing increased numbers of nociceptors do not
exhibit increased behavioral sensitivity in models of inflammatory
and neuropathic pain},
journal = {Pain},
year = {2003},
volume = {106},
pages = {491--500},
number = {3},
month = dec,
abstract = {At least two classes of nociceptors can be distinguished based on
their growth factor requirements: glial cell-line derived neurotrophic
factor (GDNF)- and nerve growth factor (NGF)-dependent primary afferent
neurons. Based on numerous anatomical and biochemical differences,
GDNF- and NGF-dependent neurons have been proposed to be involved
in the development of different types of persistent pain. To examine
this hypothesis we used two lines of transgenic mice that contained
a supernormal number of either NGF- or GDNF-dependent neurons (referred
to as NGF-OE and GDNF-OE mice, respectively). These mice were tested
in a model of inflammatory pain (induced by injection of complete
Freund's adjuvant) and neuropathic pain (using a spinal nerve ligation
protocol). Contrary to expectations, neither line of transgenic mice
became more hyperalgesic following induction of persistent pain.
In fact, NGF-OE mice recovered more rapidly and became hypoalgesic
despite extensive paw swelling in the inflammatory pain model. In
the neuropathic pain model, only wildtype mice became hyperalgesic.
Real-time PCR analysis showed that the NGF-OE and GDNF-OE mice exhibited
changes in neuronal-specific mRNAs in the dorsal root ganglia but
not the spinal cord dorsal horn. These results indicate that increasing
the number of nociceptors results in potent compensatory mechanisms
that may begin with changes in the sensory neurons themselves.},
issn = {0304-3959},
keywords = {Nerve growth factor, Nociceptors, Inflammatory and neuropathic pain,
Transcriptional analysis},
url = {http://www.sciencedirect.com/science/article/B6T0K-4B0WSF5-3/2/88fead1d7052e2f17ede7d8a43e508ef}
}
@ARTICLE{Zykova2008,
author = {Zykova, SN and Seredkina, N and Benjaminsen, J and Rekvig, OP},
title = {Reduced fragmentation of apoptotic chromatin is associated with nephritis
in lupus-prone (NZB x NZW)F(1) mice.},
journal = {Arthritis Rheumatology},
year = {2008},
volume = {58},
pages = {813-25--},
number = {3},
month = mar,
abstract = {OBJECTIVE: Antinucleosome autoantibodies are pathogenic factors in
lupus nephritis. Defects in apoptotic pathways may result in increased
levels of apoptotic nucleosomes. The objectives of this study were
1) to determine whether low molecular weight oligonucleosomes are
present in the kidneys of autoimmune (NZB x NZW)F(1) mice, 2) to
analyze whether the presence of glomerular membrane-associated TUNEL-positive
electron-dense structures reflect the existence of low molecular
weight oligonucleosomes, and 3) to determine an eventual temporal
relationship between glomerular electron-dense structures, oligonucleosomes,
and proteinuria in these mice. METHODS: DNA was isolated from mouse
111s34 hybridoma cells and from the kidneys of normal BALB/c mice
in which apoptosis was induced by camptothecin and from the kidneys
of (NZB x NZW)F(1) mice at ages 4 weeks, 8 weeks, 20 weeks, and >
or = 26 weeks (nephritic mice). The DNA fragmentation pattern was
determined with an Agilent bioanalyzer. An electron microscopy-based
TUNEL assay was performed to detect apoptotic chromatin in glomerular
membranes, and immunoelectron microscopy was used to determine antibody
binding. Transcription levels for nucleases associated with apoptosis
and necrosis were determined by real-time polymerase chain reaction.
RESULTS: DNA from camptothecin-treated cell lines and BALB/c mouse
kidneys, but not that from untreated (NZB x NZW)F(1) mouse kidneys,
demonstrated DNA cleavage consistent with apoptotic fragmentation.
DNA from (NZB x NZW)F(1) mice was devoid of apoptotic fragmentation,
irrespective of the age of the mice, whereas TUNEL-positive chromatin
particles were detected in glomerular membranes in nephritic mice.
Renal DNase I transcription was reduced in nephritic mice. Nucleosomal
DNA fragmentation in response to camptothecin exposure was highly
reduced in (NZB x NZW)F(1) mouse kidneys compared with that in their
normal counterparts. CONCLUSION: The results of this study demonstrate
that TUNEL-positive chromatin particles are deposited in the glomeruli
of nephritic (NZB x NZW)F(1) mice, due to reduced fragmentation and
clearance of chromatin.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18311834}
}
@ARTICLE{Zykova2007,
author = {Zykova, Svetlana N. And Seredkina, Natalya E. And Rekvig, Ole Petter},
title = {Glomerular Targets for Autoantibodies in Lupus Nephritis—An Apoptotic
Origin},
journal = {Annals of the New York Academy of Sciences},
year = {2007},
volume = {1108},
pages = {1--10},
number = {1},
abstract = {Abstract: Systemic lupus erythematosus (SLE) is an autoimmune syndrome
where different organs may individually or simultaneously be affected.
Whether SLE is one disease entity or represents a variety of intrinsically
unrelated organ manifestations is unknown. Variability of clinical
presentations of SLE argues against the former. This does not, however,
exclude that certain organ manifestations may be pathogenetically
linked. It is believed that in situ binding of anti-dsDNA antibodies
by nucleosomes is involved in organ manifestations in SLE. This review
will focus on nature and origin of target structures for anti-dsDNA
and anti-nucleosome antibodies in glomerular capillary and mesangial
matrix membranes. We will particularly discuss the potential role
of apoptosis and release of apoptotic chromatin in terms of their
putative impact in SLE.},
issn = {1749-6632},
keywords = {apoptosis, anti-dsDNA antibodies, DNA fragmentation, SLE, lupus nephritis},
publisher = {Blackwell Publishing Inc},
url = {http://dx.doi.org/10.1196/annals.1422.001}
}
@ARTICLE{Oesterberg2009,
author = {Österberg, Lovisa and Levan, Kristina and Partheen, Karolina and
Delle, Ulla and Olsson, Björn and Sundfeldt, Karin and Horvath, György},
title = {Potential predictive markers of chemotherapy resistance in stage
III ovarian serous carcinomas},
journal = {BMC Cancer},
year = {2009},
volume = {9},
pages = {368},
number = {1},
abstract = {BACKGROUND:Chemotherapy resistance remains a major obstacle in the
treatment of women with ovarian cancer. Establishing predictive markers
of chemoresponse would help to individualize therapy and improve
survival of ovarian cancer patients. Chemotherapy resistance in ovarian
cancer has been studied thoroughly and several non-overlapping single
genes, gene profiles and copy number alterations have been suggested
as potential markers. The objective of this study was to explore
genetic alterations behind chemotherapy resistance in ovarian cancer
with the ultimate aim to find potential predictive markers.METHODS:To
create the best opportunities for identifying genetic alterations
of importance for resistance, we selected a homogenous tumor material
concerning histology, stage and chemotherapy. Using high-resolution
whole genome array comparative genomic hybridization (CGH), we analyzed
the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas,
all uniformly treated with combination therapy paclitaxel/carboplatin.
Fisher's exact test was used to identify significant differences.
Subsequently, we examined four genes in the significant regions (EVI1,
MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time
polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations
on the transcriptional level.RESULTS:We identified gain in 3q26.2,
and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12,
Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with
chemotherapy resistance. In the gene expression analysis, EVI1 expression
differed between samples with gain versus without gain, exhibiting
higher expression in the gain group.CONCLUSION:In conclusion, we
detected specific genetic alterations associated with resistance,
of which some might be potential predictive markers of chemotherapy
resistance in advanced ovarian serous carcinomas. Thus, further studies
are required to validate these findings in an independent ovarian
tumor series.},
doi = {10.1186/1471-2407-9-368},
issn = {1471-2407},
pubmedid = {19835627},
url = {http://www.biomedcentral.com/1471-2407/9/368}
}
@ARTICLE{Oeie2011,
author = {Øie, Cristina Ionica and Appa, Rupa Shree and Hilden, Ida and Petersen,
Helle Heibroch and Gruhler, Albrecht and Smedsrød, Bård and Hansen,
John-Bjarne},
title = {Rat liver sinusoidal endothelial cells (LSECs) express functional
low density lipoprotein receptor-related protein-1 (LRP-1)},
journal = {J Hepatol},
year = {2011},
volume = {55},
pages = {1346--1352},
number = {6},
month = dec,
abstract = {The low density lipoprotein receptor-related protein-1 (LRP-1) is
a large, multifunctional endocytic receptor from the LDL receptor
family, highly expressed in liver parenchymal cells (PCs), neurons,
activated astrocytes, and fibroblasts. The aim of the study was to
investigate if liver sinusoidal endothelial cells (LSECs), highly
specialized scavenger cells, express LRP-1. To address this question,
experiments were performed in vivo and in vitro to determine if receptor
associated protein (RAP) and trypsin-activated α2-macroglobulin
(α2M∗) were endocytosed in LSECs. Both ligands were cleared from
the circulation mainly by the liver. Hepatocellular distribution
of intravenously administered ligands, assessed after magnetic bead
cell separation using LSEC- and KC-specific antibodies, showed that
PCs contained 93% and 82% of liver-associated 125I-RAP and 125I-α2M∗,
whereas 5% and 11% were associated with LSECs. Uptake of RAP and
α2M∗ in the different liver cell population in vitro was specific
and followed by degradation. The uptake of 125I-RAP was not inhibited
by ligands to known endocytosis receptors in LSECs, while uptake
of 125I-α2M∗ was significantly inhibited by RAP, suggesting the
involvement of LRP-1. Immunofluorescence using LRP-1 antibody showed
positive staining in LSECs. Ligand blot analyses using total cell
proteins and 125I-RAP followed by mass spectrometry further confirmed
and identified LRP-1 in LSECs. LSECs express functional LRP-1. An
important implication of our findings is that LSECs contribute to
the rapid removal of blood borne ligands for LRP-1 and may thus play
a role in lipid homeostasis.},
issn = {0168-8278},
keywords = {RAP, receptor associated protein, α2M∗, trypsin-activated α2-macroglobulin,
PC, parenchymal cell, FSA, formaldehyde-treated bovine serum albumin,
α-coll, collagen α-chains, HA, hyaluronan, RT, room temperature,
KC, Kupffer cell, Receptor-mediated endocytosis, Blood clearance,
RAP, α2-Macroglobulin, Lipid homeostasis},
publisher = {Elsevier,},
refid = {S0168-8278(11)00279-0},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0168827811002790?showall=true}
}
@ARTICLE{Oerbo2009,
author = {Ørbo, Anne and Moe, Bjørn T. and Grønaas, Halvor and Paulssen, Ruth
H.},
title = {Early effects of high concentrations of progesterone and Mifepristone
A gene expression study of endometrial cancer cells (Ishikawa)},
journal = {The Journal of Steroid Biochemistry and Molecular Biology},
year = {2009},
volume = {113},
pages = {139--149},
number = {1-2},
month = jan,
abstract = {Patients with endometrial hyperplasia representing preliminary stages
of endometrial cancer have shown to respond to therapy in 100% of
the cases when treated with levonorgestrel-impregnated intrauterine
device. Anti-proliferative effect has also been reported after application
of an anti-progestin impregnated intrauterine device which showed
to induce endometrial atrophy. The intention of the present study
was to obtain more information of novel therapeutic targets for hormonal
treatment in endometrial hyperplasia and endometrial cancers. Gene
expression of signaling pathways after stimulation of Ishikawa cells
with high doses of progesterone (32 [mu]M) or Mifepristone (32 [mu]M)
was performed. After using an oligo microarrays representing 24,650
human genes and 37,580 gene transcripts, 6154 genes remained after
pre-processing and filtering. This resulted in a total of 993 up-regulated
genes with 189 genes for progesterone and 255 genes for Mifepristone.
The 550 down-regulated genes were distributed with 256 genes for
progesterone, 127 genes for RU 486. The results showed that genes
presenting the epidermal growth factor (EGF)/MAP-kinase pathway were
significantly over-represented by progesterone treatment, whereas,
by Mifepristone treatment genes involved in the p53 pathway were
also up-regulated (data not shown). These genes may be interesting
as potential new therapeutic targets in endometrial hyperplasia and
endometrial cancer, as candidate genes for therapy response or as
candidate markers for tumor progression.},
issn = {0960-0760},
keywords = {Endometrial cancer cells, Gene expression, High-dose progesterone
and Mifespristone},
url = {http://www.sciencedirect.com/science/article/B6T8X-4V74XK9-3/2/e04f327483668f506ea2bc2e762b13f1}
}
@ARTICLE{Oevergaard2011,
author = {Øvergård, Aina-Cathrine and Fiksdal, Ingrid Uglenes and Nerland,
Audun Helge and Patel, Sonal},
title = {Expression of T-cell markers during Atlantic halibut (Hippoglossus
hippoglossus L.) ontogenesis},
journal = {Developmental \& Comparative Immunology},
year = {2011},
volume = {35},
pages = {203--213},
number = {2},
month = feb,
abstract = {The immune system of Atlantic halibut is relatively undeveloped at
the time of hatching, and thus larvae are vulnerable to bacterial
and viral diseases that can result in high mortalities. To enable
establishment of effective prophylactic measures, it is important
to know when the adaptive immune system is developed. This depends
on both B- and T-cell functions. In the present study the expression
of RAG1, TCR[alpha], TCR[beta], CD3[gamma][delta], CD3[var epsilon],
CD3[zeta], CD4, CD4-2, CD8[alpha], CD8[beta], Lck, and ZAP-70 was
analyzed in larval and juvenile stages during halibut development.
Using real time RT-PCR, low basal mRNA levels of all 12 genes could
be detected at early stages. An increase in mRNA transcripts for
the genes was seen at different time points, from 38 days post hatching
(dph) about the time when the first anlage of thymus is found, and
onwards. The transcription patterns of the 12 mRNAs were found to
be similar throughout the developmental stages tested. In situ hybridization
on larval cross-sections showed that RAG1 and Lck could be detected
in lymphocyte like cells within the thymus at 42 dph. CD4 expression
could not be detected within the thymus before 66 dph, however, positive
cells were restricted to the cortical region. At 87 dph, the zonation
of the thymus in a cortical, cortico-medullary, and a medullary region
seemed to be more evident with CD8[alpha] expressing cells found
in all regions, indicating the presence of mature T-cells. This correlates
with previous results describing thymus development and the appearance
of IgM+ cells during halibut ontogenesis.},
issn = {0145-305X},
keywords = {Teleost, T-cell receptor, Recombination activation gene, CD3, CD4,
CD8, Lck, ZAP-70, T-cell development, T-cell maturation},
url = {http://www.sciencedirect.com/science/article/pii/S0145305X10002302}
}
@ARTICLE{Oevergaard2009,
author = {Øvergård, Aina-Cathrine and Hordvik, Ivar and Nerland, Audun Helge
and Eikeland, Gisle and Patel, Sonal},
title = {Cloning and expression analysis of Atlantic halibut (Hippoglossus
hippoglossus) CD3 genes},
journal = {Fish \& Shellfish Immunology},
year = {2009},
volume = {27},
pages = {707--713},
number = {6},
month = dec,
abstract = {The CD3 complex is in higher vertebrates shown to be important for
the activation of T-cells. The T-cell system in fish is believed
to be similar to that in higher vertebrates, and the CD3 chains could
therefore be an important marker for identification of T-cells in
fish. Here, we report the cDNA and corresponding gene sequence of
Atlantic halibut (Hippoglossus hippoglossus) CD3[gamma][delta], CD3[var
epsilon], and CD3[zeta] chains, and the tissue-specific expression
pattern of CD3 and T- cell receptor (TCR) genes. Important structural
characteristics defining the CD3 genes seemed to be conserved in
the halibut CD3 chains, such as a signal peptide, an extracellular
region, a transmembrane helix having a negatively charged residue,
and an ITAM bearing cytoplasmic tail. The extracellular domain of
halibut CD3[gamma][delta] and CD3[var epsilon] included two cysteines
presumably involved in Ig-fold stabilisation and the CxxCxE motif
important for dimerization. A spliced variant of CD3[var epsilon]
was identified, lacking the Ig-fold, but with the CxxCxE motif intact.
The real time RT-PCR analysis revealed a highly similar expression
pattern of the CD3 genes and the TCR[alpha] and TCR[beta] genes,
indicating that the functional relationship between the TCR and the
CD3 genes are preserved in teleosts.},
issn = {1050-4648},
keywords = {CD3, Atlantic halibut, T-cell receptor, ITAM, Teleost},
url = {http://www.sciencedirect.com/science/article/B6WFN-4X60T9M-1/2/cfe13f4a5a4c4f0b0dcf4085136425ee}
}
@ARTICLE{Oevergaard2010,
author = {Øvergård, Aina-Cathrine and Nerland, Audun and Patel, Sonal},
title = {Evaluation of potential reference genes for real time RT-PCR studies
in Atlantic halibut (Hippoglossus Hippoglossus L.); during development,
in tissues of healthy and NNV-injected fish, and in anterior kidney
leucocytes},
journal = {BMC Molecular Biology},
year = {2010},
volume = {11},
pages = {36},
number = {1},
abstract = {BACKGROUND:Real time RT-PCR has become an important tool for analyzing
gene expression in fish. Although several housekeeping genes have
been evaluated in Atlantic halibut (Hippoglossus Hippoglossus L.),
appropriate reference genes for low copy mRNA transcripts at the
earliest developmental stages have not been identified. No attempts
have been reported to identify suitable reference genes in halibut
infected with NNV or in stimulated halibut leucocytes. In this study,
ß-actin1 (ACTB1), elongation factor 1 alpha (EF1A1), hypoxanthine-guanine
phosphoribosyltransferase 1 (HPRT1), ribosomal protein L7 (RPL7),
tubulin beta 2C (Tubb2C), and ubiquitin-conjugating enzyme (UbcE)
were evaluated as reference genes for normalization of real time
RT-PCR data during Atlantic halibut development, in tissue of healthy
and NNV-infected fish, and in in vivo and in vitro stimulated anterior
kidney leucocytes.RESULTS:The expression of all six genes was relatively
stable from the unfertilized egg until 12 day degrees post fertilization
(ddpf). However, none of the selected genes were found to be stably
expressed throughout halibut development. The mRNA levels of the
six genes increased from 18 ddpf, when zygotic transcription is likely
to be activated, and stabilized at different time points. The Excel-based
software programs BestKeeper, geNorm, and NormFinder ranked EF1A1
and UbcE as the best candidate reference genes before activation
of zygotic transcription, and RPL7 and EF1A1 as the best candidates
after hatching. EF1A1 and RPL7 were also listed as the best reference
genes when exploring the expression levels of the six genes in various
halibut organs, both in non-injected fish and in mock- and NNV-injected
fish. None of the reference genes were found optimal for normalization
of real time RT-PCR data from in vitro stimulated anterior kidney
leucocytes.CONCLUSION:Generally, it was found that EF1A1 and RPL7
were the genes that showed least variation, with HPRT1 and UbcE as
intermediate genes, and ACTB1 and Tubb2C as the least stable ones.
None of the six reference genes can be recommended as reference gene
candidates in ConA-PMA stimulated leucocytes. However, UbcE can be
a good candidate in other experimental setups. This study emphasizes
the need for reference gene evaluation, as universal reference genes
have not been identified.},
doi = {10.1186/1471-2199-11-36},
issn = {1471-2199},
pubmedid = {20459764},
url = {http://www.biomedcentral.com/1471-2199/11/36}
}
@ARTICLE{Oevergaard2011a,
author = {Aina-Cathrine Øvergård and Audun Helge Nerland and Ingrid Uglenes
Fiksdal and Sonal Patel},
title = {Atlantic halibut experimentally infected with nodavirus shows increased
levels of T-cell marker and IFN? transcripts},
journal = {Developmental \& Comparative Immunology},
year = {2011},
volume = {na},
pages = { - },
number = {0},
abstract = {The transcript levels of viral RNAs, selected T-cell marker and cytokine
genes, toll like receptor (TLR) 7, and two interferon stimulated
genes (ISG) were analysed in sexually immature adult Atlantic halibut
(Hippoglossus hippoglossus L.) experimentally infected with nodavirus.
The expression of the T-cell markers, TLR7 and the cytokine genes
was further explored in in vitro stimulated anterior kidney leucocytes
(AK leucocytes) isolated from the experiment fish and from additional
untreated non-injected fish. The levels of viral RNA1 and RNA2 were
increasing in brain and eye at around 4 and 8 weeks post injection
(wpi), respectively, and still increasing at the end of the experiment,
especially in eye. Immuno-positive cells and signs of vacuolisation
in both brain and eye were seen at 14 wpi. Increased transcript
levels of TCRβ, CD4-2, CD4, CD8α, and Lck in brain and eye of the
experimentally infected halibut suggested an involvement of halibut
T-cells in the immune response against nodavirus. Interestingly,
a similar expression pattern of TCRβ, CD4 and Lck was seen in both
brain and eye. However, compared to brain that showed elevated transcript
levels of TCRβ, CD4 and Lck mainly at 10 and 14 wpi, the increase
appeared earlier between 3 and 4 wpi in the eye. Yet, an increase
in the transcript level of IFNγ was seen at 10 and 14 wpi in
both organs. Moreover, elevated levels of TLR7, IL-1β, IL-6, ISG15
and Mx were detected in vivo. The in vitro experiments, stimulating
AK leucocytes with ConA–PMA, imiquimod or nodavirus, further supported
an involvement of IL-6 and IFNγ in the immune response against nodavirus
and the involvement of CD8β+ cells. Results from the present study
thus indicate an importance of T-cells, IFNγ and the analysed ISGs
in the immune response against nodavirus in Atlantic halibut, and
would be of great help in future vaccination trials giving the possibility
to monitor the immune response rather than mortality during post-vaccination
challenge experiments.},
doi = {10.1016/j.dci.2011.10.003},
issn = {0145-305X},
keywords = {T-cell receptor},
url = {http://www.sciencedirect.com/science/article/pii/S0145305X1100276X}
}
@ARTICLE{Oevergaard2010a,
author = {Øvergård, Aina-Cathrine and Nerland, Audun Helge and Patel, Sonal},
title = {Cloning, characterization, and expression pattern of Atlantic halibut
(Hippoglossus hippoglossus L.) CD4-2, Lck, and ZAP-70},
journal = {Fish \& Shellfish Immunology},
year = {2010},
volume = {29},
pages = {987--997},
number = {6},
month = dec,
abstract = {As known from mammalia, the co-receptors CD4 or CD8 associate with
a lymphocyte cell-specific kinase (Lck) upon T-cell activation. Lck
phosphorylates tyrosine residues within the CD3 chains, providing
docking sites for a 70 kDa zeta-associated-protein (ZAP-70), a tyrosine
protein kinase important for T-cell signaling. The sequences of a
CD4-like gene (CD4-2), Lck, and ZAP-70 were cloned, characterized,
and the relative expression pattern was explored in several organs
of Atlantic halibut (Hippoglossus hippoglossus L.). Important structural
features, as a signal peptide, two Ig-like domains followed by a
connecting peptide, a transmembrane region, and a CxC motif within
the cytoplasmic tail were conserved within the predicted halibut
CD4-2 protein. The deduced halibut Lck protein sequence was found
to be composed of a N-terminal Src homology (SH) 4 domain, required
for membrane attachment and CD4/CD8 binding, SH3 and SH2 adapter
domains, and a SH1 domain followed by a regulatory C-terminal tail
(COOH-domain). Tyrosine residues important in Lck activation were
conserved within the SH1 and COOH-domain. Structural features of
ZAP-70 as tandem SH2 domains and a C-terminal SH1 domain were predicted
within the halibut ZAP-70 sequence, having the highest level of conservation
within these regions. Several important phosphorylation sites found
to play a critical role in T-cell antigen receptor signaling in mammalian
were conserved. The overall expression pattern of the three genes
was highly similar, showing the highest mRNA level of all three genes
in thymus. Some expression was seen in spleen, anterior and posterior
kidney, gills, and fin, as seen for other halibut T-cell markers.
This study will enable further experiments on halibut T-cell signaling
and activation, and enhance understanding about the development of
immunological memory T-cells of halibut.},
issn = {1050-4648},
keywords = {Lymphocyte cell-specific kinase, 70 kDa zeta-associated-protein, Teleost,
T-cell},
url = {http://www.sciencedirect.com/science/article/B6WFN-50TRX6C-5/2/c72e09b6559089e6c81904e84a78d649}
}
@ARTICLE{Skugor2009,
author = {Škugor, Stanko and Jørgensen, Sven and Gjerde, Bjarne and Krasnov,
Aleksei},
title = {Hepatic gene expression profiling reveals protective responses in
Atlantic salmon vaccinated against furunculosis},
journal = {BMC Genomics},
year = {2009},
volume = {10},
pages = {503},
number = {1},
abstract = {BACKGROUND:Furunculosis, a disease caused with gram negative bacteria
Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination
against furunculosis reduces mortality of Atlantic salmon but fails
to eradicate infection. Factors that determine high individual variation
of vaccination efficiency remain unknown. We used gene expression
analyses to search for the correlates of vaccine protection against
furunculosis in Atlantic salmon.RESULTS:Naïve and vaccinated fish
were challenged by co-habitance. Fish with symptoms of furunculosis
at the onset of mass mortality (LR - low resistance) and survivors
(HR - high resistance) were sampled. Hepatic gene expression was
analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR.
Comparison of LR and HR indicated changes associated with the protection
and results obtained with naïve fish were used to find and filter
the vaccine-independent responses. Genes involved in recruitment
and migration of immune cells changed expression in both directions
with greater magnitude in LR. Induction of the regulators of immune
responses was either equal (NFkB) or greater (Jun) in LR. Expression
levels of proteasome components and extracellular proteases were
higher in LR while protease inhibitors were up-regulated in HR. Differences
in chaperones and protein adaptors, scavengers of reactive oxygen
species and genes for proteins of iron metabolism suggested cellular
and oxidative stress in LR. Reduced levels of free iron and heme
can be predicted in LR by gene expression profiles with no protection
against pathogen. The level of complement regulation was greater
in HR, which showed up-regulation of the components of membrane attack
complex and the complement proteins that protect the host against
the auto-immune damages. HR fish was also characterized with up-regulation
of genes for proteins involved in the protection of extracellular
matrix, lipid metabolism and clearance of endogenous and exogenous
toxic compounds. A number of genes with marked expression difference
between HR and LR can be considered as positive and negative correlates
of vaccine protection against furunculosis.CONCLUSION:Efficiency
of vaccination against furunculosis depends largely on the ability
of host to neutralize the negative impacts of immune responses combined
with efficient clearance and prevention of tissue damages.},
doi = {10.1186/1471-2164-10-503},
issn = {1471-2164},
pubmedid = {19878563},
url = {http://www.biomedcentral.com/1471-2164/10/503}
}