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GSE9103
Homo sapiens
34 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions.
Publication Title
Endurance exercise as a countermeasure for aging.
Sample Metadata Fields
No sample metadata fields
View Samples- Triticum aestivum
- 15 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
Water soluble carbohydrates (WSC, composed of mainly fructans, sucrose, glucose and fructose) deposited in wheat stems are important carbon sources for grain filling. Variation in stem WSC concentrations among wheat genotypes is one of the genetic factors influencing grain weight and yield under water-limited environments. Here, we describe the molecular dissection of carbohydrate metabolism in stems, at the WSC accumulation phase, of recombinant inbred SB (Seri/Babax) lines of Triticum aestivum differing in stem WSC concentrations. Affymetrix GeneChip analysis of carbohydrate metabolic enzymes revealed that the mRNA levels of two fructan synthetic enzyme families (sucrose:sucrose 1-fructosyltransferase and sucrose:fructan 6-fructosyltransferase) in the stem were positively correlated with stem WSC and fructan concentrations, while the mRNA levels of enzyme families involved in sucrose hydrolysis (sucrose synthase and soluble acid invertase) were inversely correlated with WSC concentrations. Differential regulation of the mRNA levels of these sucrose hydrolytic enzymes in SB lines resulted in genotypic differences in these enzyme activities. Down-regulation of sucrose synthase and soluble acid invertase in high WSC lines was accompanied by significant decreases in the mRNA levels of enzyme families related to sugar catabolic pathways (fructokinase and mitochondrion pyruvate dehydrogenase complex) and enzyme families involved in diverting UDP-glucose to cell wall synthesis (UDP-glucose 6-dehydrogenase, UDP-glucuronate decarboxylase and cellulose synthase), resulting in a reduction in cell wall polysaccharide contents (mainly hemicellulose) in the stem of high WSC lines. These data suggest that differential carbon partitioning in the wheat stem is one mechanism that contributes to genotypic variation in WSC accumulation.
Publication Title
Molecular dissection of variation in carbohydrate metabolism related to water-soluble carbohydrate accumulation in stems of wheat.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
Many new alternative splice forms have been detected at the transcript level using next generation sequencing (NGS) methods, especially RNA-Seq, but it is not known how many of these transcripts are being translated. Leveraging the unprecedented capabilities of NGS, we collected RNA-Seq and proteomics data from the same cell population (Jurkat cells) and created a bioinformatics pipeline that builds customized databases for the discovery of novel splice-junction peptides. Results: Eighty million paired-end Illumina reads and ~500,000 tandem mass spectra were used to identify 12,873 transcripts (19,320 including isoforms) and 6,810 proteins. We developed a bioinformatics workflow to retrieve high-confidence, novel splice junction sequences from the RNA data, translate these sequences into the analogous polypeptide sequence, and create a customized splice junction database for MS searching. Overall design: Jurkat T-cell mRNA was analyzed on an Illumina HiSeq2000. ~80 million paired end reads (2x200bp, ~350bp lengths) were collected.
Publication Title
Discovery and mass spectrometric analysis of novel splice-junction peptides using RNA-Seq.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Individuals with the ALS-linked (amyotrophic lateral sclerosis) truncation mutation (R495X) in FUS (fused in sarcoma) are known to have a more aggressive form of the disease than those with point mutations. The underlying cause for this difference is unclear. We report that FUS is a component of miRISC (miRNA-induced silencing complex) and that overexpression of its truncation mutant R495X negatively impacts miRNA mediated RNA silencing.
Publication Title
FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Pre-stimulation of MDMs with LPS (signals via MyD88 and TRIF dependent pathways) and PolyI:C (signals via a TRIF dependent pathway) leads to a reduced viral infection. In contrast, pre-stimulation with P3C (signals via MyD88 dependent pathway) does not lead to a reduced viral infection. This microarray was performed to find genes that are specifically upregulated in LPS and PolyI:C stimulated MDMs but not P3C stimulated MDMs. So to give us leads into the mechanism involved in the reduction of viral infection.
Publication Title
Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. The goal of this study was to evaluate the clinical activity and tolerability of multiple doses of SRT2104, a selective activator of SIRT1, in patients with moderate to severe psoriasis after day 84 of treatment. Forty patients were randomized 4:1 to three escalating doses of SRT2104 (250, 500, 1000 mg/d SRT2104 or placebo). Across all SRT2104 groups, 34.6% of patients (9 out of 26; 90% CI 18.0%-54.2%, p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84. To evaluate the changes in expression profile with treatment and to identify pathways involved in histological improvement, a subset of 22 Pre and Post treatment biopsies from 11 patients (4 Placebo, 7 Active Treatment) were hybridized to hgu133plus2 chips. Improvement in histology was associated with modulation of IL-17 and TNF-_ signaling pathways and keratinocyte differentiation target genes. Various studies suggest a crucial role of TNF_ and IL-17 in psoriasis pathogenesis and IL-17/TNF_ synergism induces a strong induction of differentially expressed genes in psoriasis, thus advocating a crucial role of IL-17/TNF_ combination in the molecular basis of disease (Chiricozzi et al., 2010). In the current study, broad scale gene expression profiling revealed that SRT2104 significantly reduced known IL-17 and TNF_ responsive genes including SERPINB4, S100A12, SERPINB3, kynu etc. even though the sample size for this analysis was small. One of the most highly modulated genes by SRT2104 included Kynu, a gene that regulates tryptophan metabolism, known to confer antibacterial effector functions (Daubener and MacKenzie, 1999). Interestingly kynu is part of the etanercept residual genomic profile that is not modulated by etanercept therapy even though clinical efficacy is achieved. Possibly, SRT2104 may be modulating the lipid barrier of the epidermis of psoriatic skin via modulation of keratinocyte diferentiation genes, which would be consistent with the observed improvement in skin histology. These results indicate a combinatorial effect of SRT2104 on TNF_, and IL-17 inflammatory signaling pathways and keratinocyte differentiation that could be a contributing factor towards improvement in clinical scores by the SIRT1 activator, SRT2104.
Publication Title
A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis.
Sample Metadata Fields
Treatment, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Targeting BET bromodomain proteins utilizing small molecules in an emerging anti-cancer strategy with clinical evaluation of at least six inhibitors now underway. While MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional anti-tumor activities are important. Using the Eµ-Myc model of B-cell lymphoma we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of pro-apoptotic (Bim) and anti-apoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. Eµ-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1-resistance phenotype. These studies provide important information on mechanisms apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Overall design: RNA-Sequencing of JQ1 resistant and sensitive Eµ-Myc cell lines
Publication Title
BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
How G4C2 repeat expansions in C9orf72 cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is not understood. Here, we report the first mouse model to express poly(PR), a dipeptide repeat protein synthesized from expanded G4C2 repeats. Expression of GFP-(PR)50 throughout the mouse brain yielded progressive brain atrophy, neuron5 loss, loss of poly(PR)-positive cells and gliosis, culminating in motor and memory impairments. We found that poly(PR) bound DNA, localized to heterochromatin, and caused abnormal histone methylation, lamin invaginations, decreases in HP1a expression, and disruptions of HP1a liquid phases. These aberrations of histone methylation, lamins and HP1a, which regulate heterochromatin structure and gene expression, were accompanied by repetitive element10 expression and double-stranded RNA accumulation. Thus, we uncover new mechanisms by which poly(PR) contributes to c9FTD/ALS pathogenesis. Overall design: Examination of transcriptome profiles using RNA-seq on 3 month old mice expressing PR and GR polypetides with an AAV expression vector. The Poly(PR) analysis consisted of 7 mice expressing AAV-GFP-(PR)50 and 4 AAV-GFP harvest-matched controls. The Poly(GR) analysis consisted of 4 mice expressing AAV-GFP-(GR)100 and 4 AAV-GFP harvest-matched controls.
Publication Title
Heterochromatin anomalies and double-stranded RNA accumulation underlie <i>C9orf72</i> poly(PR) toxicity.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 90 Downloadable Samples
- Illumina HiSeq 2500
Description
We have sequenced using single end and paired end sequencing GMPs, CMPs, EoPs, SiglecF+IL5ra- GMPs and eosinophils to be able to characterise this new subset of GMPs and to be able to give it some context within a lineage trajectory analysis Overall design: RNA-seq was performed on GMPs (n=2), CMPs (n=2), EoPs (n=2), Eosinophils (n=3) and SiglecF+IL5ra- GMPs isolated from C57BL/6 (n=5) and Myb hypomorphic Plt4/Plt4 mice (n=4).
Publication Title
Identification of a Siglec-F+ granulocyte-macrophage progenitor.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples