Gene expression profiles of bipolar disorder (BD) patients were assessed during both a manic and a euthymic phase and compared both intra-individually, and with the gene expression profiles of controls.
Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder.
Specimen part, Disease, Subject
View SamplesAsthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.
Sex
View SamplesAnalysis of gene expression changes due to nonviral gene delivery of DNA lipoplexes versus control in human HEK293T cells.
Microarray analysis of gene expression profiles in cells transfected with nonviral vectors.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Age, Specimen part
View SamplesHistone phosphorylation plays key roles in stress-induced transcriptional reprogramming in metazoans but its function(s) in land plants has remained relatively unexplored. Here we report that an Arabidopsis mutant defective in At3g03940 and At5g18190, encoding closely related Ser/Thr protein kinases, shows pleiotropic phenotypes including dwarfism and hypersensitivity to osmotic/salt stress. The double mutant has reduced global levels of phosphorylated histone H3 threonine 3 (H3T3ph), which are not enhanced, unlike the response in the wild type, by drought-like treatments. Genome-wide analyses revealed increased H3T3ph, slight enhancement in trimethylated histone H3 lysine 4 (H3K4me3), and a modest decrease in histone H3 occupancy in pericentromeric/knob regions of wild type plants under osmotic stress. However, despite these changes in heterochromatin, transposons and repeats remained largely transcriptionally repressed. In contrast, this reorganization of heterochromatin was mostly absent in the double mutant, which even under normal conditions exhibited lower H3T3ph levels in pericentromeric regions, and a few transposons and repeat sequences showed modest transcriptional activation. Interestingly, within actively transcribed protein-coding genes, H3T3ph density was minimal in 5 genic regions, coincidental with a peak of H3K4me3 accumulation. This pattern was not affected in the double mutant, implying the existence of additional H3T3 protein kinases in Arabidopsis. Our results suggest that At3g03940 and At5g18190 are involved in the phosphorylation of H3T3 in pericentromeric/knob regions and that this repressive epigenetic mark may be important for maintaining proper heterochromatic organization and, possibly, chromosome function(s).
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Age, Specimen part
View SamplesTrans-10, cis-12 conjugated linoleic acid (t10c12 CLA) causes dramatic reductions in white adipose tissue in mice but has had limited effectiveness in humans. Determination of the signaling pathways involved may lead to better regulation of adiposity. T10c12 CLA was found to activate AMP-activating protein kinase (AMPK), a central regulator of cell metabolism. Compound C, a potent inhibitor of AMPK, prevents many of the typical responses to treatments with t10c12 CLA including the integrated stress response (ISR), the inflammatory response, the reduction in key lipogenic transcription factors, and delipidation. Treatment of adipocytes or mice with t10c12 CLA in conjunction with AMPK activator metformin results in more delipidation than treatment with the individual chemicals. Additionally, the combination showed a reduced inflammatory response relative to a t10c12 CLA treatment alone. The combination of t10c12 CLA and metformin, widely used to treat insulin resistance and Type II diabetes, has potential as a treatment for reducing adiposity in humans.
Conjugated linoleic acid activates AMP-activated protein kinase and reduces adiposity more effectively when used with metformin in mice.
Cell line
View SamplesActivated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes.
Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes.
Specimen part, Cell line, Treatment
View SamplesThe aim was to investigate mechanisms contributing to quercetins previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 M quercetin stabilized by 1mM ascorbate reduced Caco-2 differentiation up to 50% (P<0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips, showed 1,743 affected genes on both days (P<0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (P<0.01), including intestinal alkaline phosphatase that was confirmed technically (qRT-PCR) and functionally (enzyme-activity).
Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer.
No sample metadata fields
View SamplesTrans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture. The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Cell line
View SamplesTrans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT). The early transcriptome changes in WAT were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sex, Specimen part
View Samples