Eptstein-Barr Virus, an oncogenic herpesvirus, infects and immortalizes human B cells in culture into indefinitely-proliferating LCLs. We examined the gene expression of primary B cells during the process of infection and growth transformation at the exon level to analyze early and late virus-induced changes in expression and exon usage.
An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.
Specimen part
View SamplesWe identified a small zinc finger protein, MBS, as a new mediator of singlet oxygen responses in Chlamydomonas and Arabidopsis. MBS is required for induction of singlet oxygen-dependent gene expression and, upon oxidative stress, accumulates in distinct granules in the cytosol of Arabidopsis cells. First, we recorded changes in light stress-regulated gene expression profiles after genetically perturbing MBS function by isolating mutants for the two MBS genes (MBS1 and MBS2) and by overexpression of MBS1 in Arabidopsis thaliana. Then, these light stress-related gene expression profiles were analyzed with respect to genes specifically responding to singlet oxygen and hydrogen peroxide/superoxide. The results indicated that MBS inactivation leads to an impaired response to singlet oxygen signaling under light stress.
A mediator of singlet oxygen responses in Chlamydomonas reinhardtii and Arabidopsis identified by a luciferase-based genetic screen in algal cells.
Specimen part, Treatment
View SamplesAging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARa, PPAR?, and LXRa in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARa targets contributing to gene expression changes that lead to steatosis in aged liver. Overall design: Genome-wide expression profiles (RNA-Seq) from young (3 months) and old (21 months) mouse livers
Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver.
No sample metadata fields
View SamplesThe S1 and S3 erythroid developmental subsets were isolated using flow cytometry and the cell surface markers CD71 and Ter119 as described by Pop et. al. 2010 (PMID: 20877475)
Global DNA demethylation during mouse erythropoiesis in vivo.
Specimen part
View SamplesGene Expression profiling of HSCs isolated at different stages of ontogeny to address correlation between gene expression and changes in DNA methylation
Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging.
Sex, Age, Specimen part
View SamplesEstablishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that indomethacin and nimesulide influence expression of some genes among which are those coding for enzymes required for synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of indomethacin and nimesulide at the molecular level in terms of modulation of gene expression by these substances.
Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways.
Cell line
View SamplesHemagglutinin of the influenza virus is the main external glycoprotein. This very immunogenic protein is the target of the most anti-influenza vaccines. DNA vaccines are new alternative to conventional inactivated ones. Four DNA vaccines were tested. Each tested variant was based on the pCI vector with nucleotide sequence encoding hemagglutinin from A/swan/Poland/305-135V08/2006 (H5N1, clade 2.2). In K3/pCI, GK/pCI and HAneo/pCI the different optimization algorithms of hemagglutinin encoding sequence without amino acids change were tested. In 3NF/pCI the NFkappaB binding sites flanking the expression cassette were included in order to improve the nuclear transfer. Comparative transcriptome analysis of mice vaccinated the following vaccine HAneo/pCI,K3/pCI, GK/pCI or 3NF/pCI versus empty vector demonstrated minor changes in genes expression pattern. Most genes were expressed on the similar level in the vaccinated individuals and in the control mice. Small number of genes in particular variants showed the expression different than in the control mice. In general, the identified genes with the changed expression included some genes involved in metabolic processes and none of them seem to induce any undesirable pathways nor disease.
Immunogenicity of DNA Vaccine against H5N1 Containing Extended Kappa B Site: <i>In Vivo</i> Study in Mice and Chickens.
Sex, Specimen part, Treatment
View SamplesUrothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer.
Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer.
Sex
View SamplesIn addition to being causally linked to the formation of multiple tumor types, tobacco use has been associated with decreased anticancer treatment efficacy and reduced survival time. A detailed understanding of the cellular mechanisms that are affected by tobacco smoke should facilitate the development of improved preventive and therapeutic strategies. We have investigated the effects of a tobacco smoke (TS) extract on the transcriptome of MSK-Leuk1 cells, a cellular model of oral leukoplakia. Using Affymetrix HGU133 Plus 2 arrays, 411 differentially expressed probesets were identified. The observed transcriptome changes were grouped according to functional information, and translated into molecular interaction network maps and signaling pathways. Pathways related to cellular proliferation, inflammation, apoptosis and tissue injury appeared to be perturbed. Analysis of networks connecting the affected genes identified specific molecular interactions, hubs and key transcription regulators affected by TS. Thus TS was found to induce several EGFR ligands forming an EGFR-centered molecular interaction network, as well as several AhR-dependent genes, including the xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Notably, the latter findings in vitro are consistent with our parallel finding that levels of CYP1A1 and CYP1B1 were increased in oral mucosa of smokers. Collectively, these results offer insights into the mechanisms underlying the procarcinogenic effects of TS and raise the possibility that inhibitors of EGFR or AhR signaling will prevent or delay the development of tobacco smoke-related tumors. Moreover, the inductive effects of TS on xenobiotic metabolizing enzymes may help explain reduced efficacy of chemotherapy, and suggest targets for chemopreventive agents in smokers.
Effects of tobacco smoke on gene expression and cellular pathways in a cellular model of oral leukoplakia.
No sample metadata fields
View SamplesMembers of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared to other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We measured gene expression (Human Gene 1.0 ST Array, Affymetrix) in two series of experiments involving cells that were either susceptible or not susceptible to RV-C infection. In one experimental series, susceptible cells included whole sinus mucosal tissue specimens (n = 5), epithelial cell suspension from sinus tissue, and nasal epithelium obtained via brushing, while non-susceptible cells included monolayers of primary undifferentiated epithelial cells and transformed cell lines (n = 5). In a second experimental series, we compared three pairs of undifferentiated and fully differentiated (ALI) sinus epithelial cell cultures. We identified a total of 12 genes upregulated in RV-C susceptible cells (represented by 14 probe sets) encoding proteins localized to plasma membrane, and/or with predicted or functionally demonstrated receptor activity, including members of the Human MHC class II, stomatin, guanine nucleotide-binding, type I cytokine and atypical chemokine receptor and cadherin protein families.
Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.
Specimen part, Cell line, Subject
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