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GSE16381
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Metabolically active cells require robust mechanisms to combat oxidative stress. The cytoplasmic thioredoxin reductase/thioredoxin (Txnrd1/Txn1) system maintains reduced protein dithiols and provides electrons to some cellular reductases, including peroxiredoxins.
Publication Title
Cytoprotective Nrf2 pathway is induced in chronically txnrd 1-deficient hepatocytes.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 48 Downloadable Samples
Illumina HiSeq 2000
Description
Dietary restriction (DR) and loss of the genes rsks-1 and daf-2 increase longevity in C. elegans. Polysome profiling allows actively translated mRNA bound by multiple ribosomes to be isolated and compared to the total mRNA present. In this project, we differentiate transcriptional and translational changes in gene expression in C. elegans by combining polysome profiling and mRNA-sequencing. By comparing gene abundance between the two RNA pools, genes with altered translational regulation under DR and in the mutant can be identified. Overall design: Total and polysome bound RNA was isolated from well-fed daf-2;rsks-1 double mutants, well-fed N2, and dietary restricted N2 C. elegans in biological quadruplicate. Age syncronized worms were maintained at 20°C and subject to DR starting at day one of adulthood in the presence of FuDR to prevent contamination of progeny. Whole worms were lysed at day four of adulhood and the lysate was subject to polysome profiling to isolate RNA bound to 2 or more ribosomes. A aliquot of unprocessed lysate was used for RNA extraction of total RNA. RNA was enriched for polyadenylated transcripts and used for unstranded paired-end library synthesis with a Tru-seq RNA kit. Read length of 100 bp were generated using Illumina HiSeq 2000. Reads were aligned to the C.elegans genome as guided by gene annotations from ensemble version 66. Processed data contains the unfiltered counts per million (CPM) of normalized reads aligning to each gene for each of the samples submitted.
Publication Title
Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene-level transcriptome analysis of monocyte mRNA derived from mice that are genetically deficient of the Ccl2 gene or Ccr2 gene
Publication Title
CCL2/CCR2 Regulates the Tumor Microenvironment in HER-2/neu-Driven Mammary Carcinomas in Mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The oral cavity is the persistent reservoir for EBV with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns that are regulated by epigenetic modifications involving DNA methylation and chromatin structure. Such regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may inadvertently result in long-lasting, oncogenic host epigenetic reprogramming. To test this hypothesis in the context of EBV infection of epithelial cells, we established a transient infection model to identify the epigenetic consequences after EBV infection of immortalized normal oral keratinocytes and subsequent viral loss.
Publication Title
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 57 Downloadable Samples
- Illumina HiSeq 4000
Description
Whole blood RNA-seq was leveraged to explore gene expression changes induced in mice 24 hours after immunisation with a second dose of a licensed vaccine against capsular group B meningococcus, one of the vaccines components, or one of several comparator groups. Overall design: mRNA was profiled from RNA extracted from mouse whole blood, 5-6 samples per group, using an Illumina HiSeq4000
Publication Title
Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myocarditis is an inflammatory disease in the heart and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into three phases; the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the three phases of myocarditis. Theilers murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, and can cause myocarditis in susceptible mouse strains. Using this novel model for viral myocarditis induced with TMEV, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray for identifying the biomarker candidates that discriminate the three phases. Using C3H mice infected with TMEV on 4, 7, and 60 days post infection (p.i.), we conducted bioinformatics analyses, including principal component analysis (PCA) of microarray data, since our traditional cardiac and serum assays, including two-way comparison of microarray data, did not lead to the identification of a single biomarker. PCA separated heart samples clearly between the groups of 4, 7, and 60 days p.i. Representative genes contributing to the separation were as follows: 4 and 7 days p.i., innate immunity-related genes, such as Irf7, and Cxcl9; 7 and 60 days p.i., acquired immunity-related genes, such as Cd3g and H2-Aa; and cardiac remodeling-related genes, such as Mmp12 and Gpnmb. Here, sets of molecules, but not a single molecule, identified by the unsupervised PCA, were found to be useful as the phase-specific biomarkers.
Publication Title
Bioinformatics multivariate analysis determined a set of phase-specific biomarker candidates in a novel mouse model for viral myocarditis.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Recent data demonstrate that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways. This network model suggests why inhibition of a single component of a canonical pathway, even when targeting a mutationally activated driver of cancer, has insufficiently dramatic effects on the treatment of cancer. The biological outcome of signals propagated through a network is inherently more robust and resistant to inhibition of a single network component due to compensatory and redundant signaling events. In this study, we performed a functional chemical genetic screen analogous to synthetic lethal screening in yeast genetics to identify novel interactions between signaling inhibitors that would not be predicted based on our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. Among the most robust and surprising results was synergy between sorafenib, a multi-kinase inhibitor with activity against Raf, and diclofenac, a non-steroidal anti-inflammatory drug (NSAID). This synergy did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. The NSAIDs celecoxib and ibuprofen could qualitatively substitute for diclofenac. Similarly, the MEK inhibitor PD325901 and the Raf inhibitor RAF265 could qualitatively substitute for sorafenib. These drug substitution experiments suggest that inhibition of cyclo-oxygenase and MAP kinase signaling are components of the observed synergistic cytotoxicity. Genome-wide expression profiling demonstrates synergy-specific down-regulation of survival-related genes. This study provides proof of principle that synthetic lethal screening can uncover novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially depending on unexplored components of the cell genotype.
Publication Title
Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 14 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA).
Publication Title
A rosemary extract enriched in carnosic acid improves circulating adipocytokines and modulates key metabolic sensors in lean Zucker rats: Critical and contrasting differences in the obese genotype.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Non-symbiotic hemoglobins are ubiquitously expressed proteins known to interact with nitric oxide, an inhibitor of mitochondrial respiration and an important signalling component. We evaluated the underlying molecular mechanisms of AtHb1 (also referred as AtGLB1 or AHb1) function, its effects on stress response and the interplay with nitric oxide. For this purpose, AtHb1 was overexpressed in Arabidopsis thaliana under control of the seed-specific promoter LeB4.
Publication Title
Seed-specific elevation of non-symbiotic hemoglobin AtHb1: beneficial effects and underlying molecular networks in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Treatment
View Samples