These experiments were designed to detect transcript (mRNA) changes in whole circulating blood in animals exposed to D-amphetamine under neurotoxic and non-neurotoxic conditions, or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The study objectives were: 1) to detect transcript changes in blood due to life-threatening hyperthermia produced by elevated environmental temperatures (39°C, produces no or minimal neurotoxicity); 2) detect transcripts that could serve as biomarkers specific for neurotoxic amphetamine exposures and not seen with environmentally-induced hyperthermia; and 3) determine the transcript changes related to the immune system in circulating blood produced by either non-neurotoxic or neurotoxic amphetamine exposures. Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood Overall design: Five groups of animals were necessary to meet the study objectives. All groups were given 4 injections of either normal saline or amphetamine, and the injections were sequentially given with 2 h between each injection. Dosing started at 7:30 to 8:30 a.m. The groups are: 1) normothermic controls given normal saline in a 22.5°C environment; 2) controls given normal saline in a 16°C environment (also remained normothermic); 3) environmentally-induced hyperthermia given saline in a 39°C environment; 4) non-neurotoxic amphetamine given in a 16°C environment and 5) neurotoxic amphetamine group given amphetamine in a 22.5°C environment. Note the the saline controls (normothermic data) is contained in a separate but linked GEO file GSE62368
Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.
No sample metadata fields
View SamplesWe report an applicaton of small RNA sequencing using high throughput next generation sequencing to identify the small RNA content of cell lines. By sequencing over 30 million reads we could identify a new class of small RNAs previousy observed with tiling arrays and mapping to promoter regions of coding genes. We also identified a large number of small RNAs corresponding to internal exons of coding genes. By using different enzymatic treatments and immunoprecipitation experiments, we have determined that both the promoter associated small RNAs as well as ones within the body of the genes bear 5'' cap structures. Overall design: Examination of the expression of small RNAs (<200nt).
Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGene expression analysis of wid type and Lmnb1-/- epicardial cells Overall design: Total RNA was isolated from wild type and Lmnb1-/- epicardial explants and subject ot sequencing on the Illumina platform
Lamin-B1 contributes to the proper timing of epicardial cell migration and function during embryonic heart development.
Cell line, Subject
View SamplesSchizophrenia-associated miRNA were bidirectionally modulated in HEK-293, HeLa, and SH-SY5Y cell models. Results provide important insights into the current understanding of miRNA function in various cellular environments.
Alternative mRNA fates identified in microRNA-associated transcriptome analysis.
Cell line, Treatment
View SamplesIL-10 is an anti-inflammatory cytokine that has been shown to be produced by antigen-specific CD8 T cells at the peak of viral encephalitis. We found that IL-10+CD8 T cells are more activated and cytolytic than IL-10-CD8 T cells.
Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis.
Specimen part
View SamplesBackground: Mutations in the cone-rod-homeobox protein CRX are typically associated with dominant blinding retinopathies with variable age of onset and severity. Five well-characterized mouse models carrying different Crx mutations show a wide range of disease phenotypes. To determine if the phenotype variability correlates with distinct changes in CRX target gene expression, we perform RNA-seq analyses on three of these models and compare the results with published data. Results: Despite dramatic phenotypic differences between the three models tested, graded expression changes in shared sets of genes are detected. Phenotype severity correlates with the down-regulation of genes encoding key rod and cone phototransduction proteins. Interestingly, in increasingly severe mouse models, the transcription of many rod-enriched genes decreases decrementally, whereas that of cone-enriched genes increases incrementally. Unlike down-regulated genes, which show a high degree of CRX binding and dynamic epigenetic profiles in normal retinas, the up-regulated cone-enriched genes do not correlate with direct activity of CRX, but instead likely reflect a change in rod cell-fate integrity. Furthermore, these analyses describe the impact of minor gene expression changes on the phenotype, as two mutants showed marginally distinguishable expression patterns but huge phenotypic differences, including distinct mechanisms of retinal degeneration. Conclusions: Our results implicate a threshold effect of gene expression level on photoreceptor function and survival, highlight the importance of CRX in photoreceptor subtype development and maintenance, and provide a molecular basis for phenotype variability in CRX-associated retinopathies. Overall design: All genotypes were analyzed in triplicate. Heterozygous and homozygous mutants were all sequenced at P10, the control for which is the P10 C57BL6/J data. Heterozygous mutants were also analyzed at P21, the control for which is the P21 C57BL6/J data.
Graded gene expression changes determine phenotype severity in mouse models of CRX-associated retinopathies.
No sample metadata fields
View SamplesThe Keap1/Nrf2 signaling pathway is a tractable target for the pharmacological prevention of tumorigenesis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two classes of Nrf2-activating chemopreventive agents. Natural dithiolethiones have been widely used in clinical trials for cancer chemoprevention. Synthetic triterpenoids, however, have been shown to be significantly more potent Nrf2 activators and are under clinical evaluation for the treatment of chronic kidney disease. This study seeks to characterize the structure-activity relationship between D3T and CDDO-Im in mouse liver tissue. To this end we treated Wt and Nrf2-null mice with 300 umol/kg bw D3T and 3, 10, and 30 umol/kg bw CDDO-Im every other day for 5 days and evaulated global gene expression changes as a product of both treamtent and genotype using Affymetrix microarray.
Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo.
Sex, Age, Specimen part
View SamplesOBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.
Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
No sample metadata fields
View SamplesYeast transcription factor Yap1 mediates adaptive response against H2O2 and the cystein thiol reactive Michael acceptor, N-ethylmaleimid (NEM) and acrolein. The response against H2O2 was found to be distinct from that against NEM and acrolein.
Yap1 activation by H2O2 or thiol-reactive chemicals elicits distinct adaptive gene responses.
Treatment
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