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GSE28750
Homo sapiens
41 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: Sepsis is a complex immunological response to infection characterized by early hyperinflammation followed by severe and protracted immunosuppression, suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on SIRS differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing.
Publication Title
Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Recent evidence supports a role for RNA as a common pathogenic agent in both the polyglutamine and untranslated dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcripts as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease associated repeat sequences - CAG, CUG and AUUCU - were specifically expressed in the neurons of Drosophila and resultant common, early, transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3- signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.
Publication Title
Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background
Publication Title
Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The WWOX gene spans chromosomal fragile site FRA16D, a region of DNA instability in cancer. While WWOX has some tumor suppressor characteristics, its normal role and functional contribution to cancer are unclear. Drosophila homozygous Wwox mutants are viable with no discernable phenotype. Drosophila Wwox interactors, identified by proteomics and micro-array analyses, mainly have roles in aerobic metabolism. Functional relationships between Wwox and either isocitrate dehydrogenase (IDH) or superoxide dismutase 1 (Sod1) were confirmed by phenotype modification, including Sod1 crinkled-wing, indicative of oxidative stress response. Endogenous reactive oxygen species levels reflect Wwox levels in Drosophila. WWOX mRNA levels in Drosophila and human cells correlate with IDH and Sod1 levels. Wwox therefore contributes to pathways involving glucose metabolism and oxidative stress response.
Publication Title
Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Dominantly inherited expanded repeat neurodegenerative diseases are typically caused by the expansion of existing variable copy number tandem repeat sequences in otherwise unrelated genes. Repeats located in translated regions encode polyglutamine that is thought to be the toxic agent, however in several instances the expanded repeat is in an untranslated region, necessitating multiple pathogenic pathways or an alternative common toxic agent. As numerous clinical features are shared by several of these diseases, and expanded repeat RNA is a common intermediary, RNA has been proposed as a common pathogenic agent. Various forms of repeat RNA are toxic in animal models, by multiple distinct pathways. In Drosophila, repeat-containing double-stranded RNA (rCAG.rCUG~100) toxicity is dependent on Dicer processing evident with the presence of single-stranded rCAG7, which have been detected in affected HD brains. Microarray analysis of Drosophila rCAG.rCUG~100 repeat RNA toxicity revealed perturbation of several pathways including innate immunity. Recent reports of elevated circulating cytokines prior to clinical onset, and age-dependent increased inflammatory signaling and microglia activation in the brain, suggest that immune activation precedes neuronal toxicity. Since the Toll pathway is activated by certain forms of RNA, we assessed the role of this pathway in RNA toxicity. We find that rCAG.rCUG~100 activates Toll signaling and that RNA toxicity is dependent on this pathway. The sensitivity of RNA toxicity to autophagy further implicates innate immune activation. Expression of rCAG.rCUG~100 was therefore directed in glial cells and found to be sufficient to cause neuronal dysfunction. Non-autonomous toxicity due to expanded repeat-containing double-stranded RNA mediated activation of innate immunity is therefore proposed as a candidate pathway for this group of human genetic diseases.
Publication Title
Distinct roles for Toll and autophagy pathways in double-stranded RNA toxicity in a Drosophila model of expanded repeat neurodegenerative diseases.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Data reveal that smokers exhibit distinct gene expression profiles relative to non-smokers and moist snuff consumers. Moist snuff consumer gene expression largely resembles that of non-tobacco consumers.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of non-differentiated Caco-2 intestinal epithelial cell line treated with polydextrose fermentation metabolites fermented for 48 hours in 4-stage in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse and distal colon in sequence , as well as with medium, 100 mM NaCl and 5 mM butyrate. Polydextrose, a soluble fiber fermented in colon, was fermented with the in vitro colon simulator in three amounts of 0%, 1% and 2%. Results provide insight into the mechanisms underlying colon cancer cells and a comparison of a complex fiber metabolome to 5 mM butyrate and 100 mM NaCl. Furthermore, the results give insight of dosage effect of increasing the concentration of fiber.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 200 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motives we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified co-regulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B cell and T cell infiltration. We calculated metagenes as surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation associated genes. In multivariate Cox regression analysis the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort (Hazard Ratio (HR) 2.20, 95% confidence interval (CI) 1.40-3.46). The B cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR 0.66, 95% CI 0.46 - 0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high grade tumors (n=286, HR 0.78, 95% CI 0.62-0.98), and a second validation cohort enriched for younger patients (n=302, HR 0.83, 95% CI 0.7-0.97). Thus, we could demonstrate in three cohorts of untreated node-negative breast cancer patients, that the humoral immune system plays a pivotal role for metastasis-free survival of carcinomas of the breast.
Publication Title
The humoral immune system has a key prognostic impact in node-negative breast cancer.
Sample Metadata Fields
Disease stage
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Signalling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages which are a source of the somatic growth factor insulin growth factor 1 (IGF1). Treatment of newborn mice with CSF1 has previously been shown to produce an increase in somatic growth rate and we hypothesised that treatment of neonatal low birth weight (LBW) rats with CSF1 would do the same. Growth rates were not affected, yet CSF1 treatment caused an unexpectedly large, but reversible increase in liver size and hepatic fat deposition in both normal and LBW rats. By transcriptional profiling, we have highlighted numerous CSF1-regulated genes known to be involved in lipid droplet formation in the liver and novel candidate genes for further investigation. In contrast to mice and weaner pigs, CSF1 treatment did not increase hepatocyte proliferation in neonatal rats, rather the data were consistent with increased macrophage proliferation instead. This suggests that Kupffer cells promote lipid accumulation in neonates and treatment to ablate CSF1R signalling may reverse lipid accumulation in the liver.
Publication Title
Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression in the mouse brain following early pregnancy exposure to ethanol.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples