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GSE31901
Homo sapiens
56 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance.
Publication Title
PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity.
Sample Metadata Fields
Sex, Age, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) has a functional role in human PBMCs during fasting. However, the extent of the role of PPAR in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPAR ligand WY14,643. Results: Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPAR activation between six healthy human blood donors, which was not the result of the nutritional status of the donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in -oxidation were up-regulated upon activation of PPAR with WY14,643, and genes in several amino acid metabolism pathways were down-regulated. Conclusions: This study shows that PPAR in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We show that PBMCs are a suitable model to study changes in PPAR activation in healthy humans.
Publication Title
Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exercise training or pathological stimuli eg pressure or volume overload. Majority of new therapies for heart failure has mixed outcomes. A combined mouse model and oligo-array approach are used to examine whether phosphoinositide 3-kinase (p110-alpha isoform) activity is critical for maintenance of cardiac function and long-term survival in a setting of heart failure. The significance and expected outcome are to recognise genes involved in models of heart failure ie pathological- vs physiology-hypertrophy, and examine the molecular mechanisms responsible for such activity.
Publication Title
PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol_II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adapter protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1/COMPASS H3K4 methyltransferase and the nuclear Protein Phosphatase 1 (PP1) complexes to the initiating Pol_II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1 or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes, active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs. Overall design: polyA-mRNAs or 4sU-labeled RNAs from BMDMs, either untreated or treated for with lipopolysaccharide (LPS) for the indicated time. Experiments were carried out in cells containing either a short hairpin targeting either of these: 1) Wdr82; 2) Set1a+Set1b; 3) Pnuts; or the empty vector (LMP) or a scrambled as a control. When specified, cells were pre-treated with 5,6-Dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) in order to prevent RNA polymerase II elongation.
Publication Title
Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 4000
Description
How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer. Overall design: Nuclear RNA profiling in lymphoblastoid TK6 cell line
Publication Title
Spatial Chromosome Folding and Active Transcription Drive DNA Fragility and Formation of Oncogenic MLL Translocations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the CD4+ T cell cytokines responsible for the proliferation of the Lin-IEL lines CD4+ T cell clone L10, which recognises DQ2-glia-1, one of the immunodominant T cell epitopes in celiac disease, was stimulated for 3 hours in IMDM with plate-bound CD3/CD28-specific (2.5 g/ml each) or control antibodies coated onto 6-well non-tissue culture treated plates. Three independent biological replicates were performed, each time including 6 million Ficoll-purified live cells per condition. RNA was purified from these cells using the RNAeasy mini kit (Qiagen, Venlo, the Netherlands). cDNA was amplified using the Applause WT-Amp system (NuGEN technologies, Bemmel, the Netherlands) and biotin-labelled with the Encore Biotin Module (NuGEN). Human Gene 1.0 ST arrays (Affymetrix, High Wycombe, UK) were employed to quantify global gene expression.
Publication Title
CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cyclophilin binding drugs, NIM811 and cyclosporin A (CsA), inhibit the replication of HCV replicon.
Publication Title
Multiple cyclophilins involved in different cellular pathways mediate HCV replication.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established
Publication Title
YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established
Publication Title
YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples