An efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Specimen part
View SamplesThe identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.
Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesHuman skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.
Specimen part, Disease, Disease stage
View SamplesSpecimens were collected from esophageal adenocarcinoma patients undergoing esophagectomy for adenocarcinoma at the University of Michigan Health System between 1991 and 2004. Written consent was obtained from each patient according to the approval and guidelines of the University of Michigan institutional review board. Patients receiving treatment with chemotherapy and/or radiotherapy prior to surgery were excluded.
Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome.
Sex, Specimen part, Disease, Cell line
View SamplesmRNA from wild-type (Cre-) and MLL1-deficient (Cre+) BMDMs were analyzed via gene chip (Mouse Gene ST 2.1, Affymetrix) for relative expression changes. Isolated mRNA from Cre- and Cre+ BMDMs stimulated with classical activation signals (IFNg, LPS or IFNg+LPS) was analyzed using a gene chip panel of >40,000 RefSeq transcripts, and resulting fold expression was determined by analyzing quality-controlled expression values for validated probesets.
The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages.
No sample metadata fields
View SamplesThoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress.
Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation.
Specimen part, Treatment
View SamplesDuring malaria infection is observed a robust immune response culminating on release of inflammatory mediators. This exacerbated immune response is involved in malaria symptoms and mortality. There are evidences that this response is mediated by innate immunity where pattern recognition receptors have a key role. We used microarrays to elucidate some pro-inflammatory genes that are differential expressed during P. chabaudi infection, a malarial murine model
Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.
Sex, Age, Specimen part
View Samples