Forty male C57BL6 mice 12-15 weeks old fed chow ad libitum. 30 mice underwent adrenalectomy (Adx) and 10 others a sham-Adx. Three or 24h before tissue sampling, groups of 10 mice received an I.P. injection of cortisol (0.1 mg per mice), while the remaining Adx and intact mice received an I.P. injection of the vehicle (ethanol) 24 h prior to the sacrifice. All mice were killed within a period of a few hours. Gastrocnemius muscle were dissected and pooled together for each one of the four groups. Total RNA was isolated by Trizol. Samples were processed following the labeling protocol from Affymetrix. In the MG-U74A2, each of the 12488 murine transcripts are represented by 16 probe pairs of 25mer. Images were scanned using a GeneChip scanner 3000 with autoloader, and analyzed with the MAS 5.0 software (Affymetrix). The ratio of fluorescence intensities for the 5' end and the 3' end of beta-actin and glyceraldehyde 3-phosphate dehydrogenase was less than 2. This microarray analysis was performed once.
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View SamplesWe explored gene expression profile of human aortic valves in patients with or without aortic stenosis. The dataset that we generated constitutes a large-scale quantitative measurements of gene expression in normal and stenotic human valves. The goal was to compare gene expression levels between the two groups and identified a list of genes that are up- or down-regulated in aortic stenosis.
Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves.
Sex, Age
View SamplesStudied gene regulation in bronchial smooth muscle cells following vitamin D stimulation.
1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes.
Sex, Age, Specimen part, Race
View SamplesUncontrolled microglial activation may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation. Using an in vivo model-system for analysis of the dynamic translational state of microglial ribosomes with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly up-regulated and ribosome-associated mRNAs were not translated resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3UTR-mediated mechanism involving the RNA binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia.
Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts.
Treatment
View SamplesTemporal changes of the expression levels of the complete human transcriptome during the first 24 hours following infection of IFN-pre-treated macrophages. This approach has allowed us to identify genes involved in the IFN signaling that have an impact on HIV-1 infection of macrophages
TRAF6 and IRF7 control HIV replication in macrophages.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line, Treatment
View SamplesWhether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line
View SamplesThe objective of this analysis was to identify the genes that are differentially expressed between preadipocytes with low or high adipogenic capability
Amplification of Adipogenic Commitment by VSTM2A.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Specimen part, Cell line
View SamplesReprogramming of cellular metabolism plays a central role in fuelling malignant transformation, and AMPK as well as the PGC-1/ERR axis are key regulators of this process. Intersection of gene expression and binding event datasets in breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1/ERR and promotes the binding of ERR to its cognate sites. Unexpectedly, the data also reveal that ERR, in concert with PGC-1, negatively regulates the expression of several one-carbon metabolism genes resulting in substantial perturbations in purine biosynthesis. This PGC-1/ERR-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1/ERR axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer.
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Cell line
View Samples