This SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesReveal differentially regulated genes and cellular pathways within allergic and non-allergic asthmatic children compared to healthy controls
No associated publication
Specimen part
View SamplesDuring fermentation Saccharomyces yeast produces various aroma-active metabolites determining the different characteristics of aroma and taste in fermented beverages. Amino acid utilization by yeast during brewers wort fermentation is seen as linked to flavour profile. To better understand the relationship between the biosynthesis of aroma relevant metabolites and the importance of amino acids, DNA microarrays were performed for Saccharomyces cerevisiae strain S81 and Saccharomyces pastorianus var. carlsbergensis strain S23, respectively. Thereby, changes in transcription of genes were measured, which are associated with amino acid assimilation and its derived aroma-active compounds during fermentation.
No associated publication
No sample metadata fields
View SamplesExpression profiles of 28 murine pancreatic cancer cell lines isolated from a KrasG12D-based mouse model of pancreatic cancer
No associated publication
Specimen part, Cell line
View SamplesBACKGROUND AND AIMS: Loss of epithelial cell homeostasis and apoptosis highly con-tribute to intestinal inflammation. While endoplasmic reticulum unfolded protein response (UPR) has been implicated in chronic intestinal inflammation, functional correlation between UPR-related C/EBP homologous protein (CHOP) expression and CHOP-mediated programming towards inflammation-related disease susceptibility remains unclear. In this study, we generated the new mouse model ChopIEC Tg/Tg to investigate consequences of intestinal epithelial cell (IEC)-specific CHOP overexpression. Transcriptional profiling of transgenic mice identified a set of CHOP-dependent target genes related to inflammatory and microbial defense program in the intestinal epithelium.
No associated publication
Sex, Age, Specimen part
View SamplesThe genome of vertebrates contains endogenous retroviruses (ERVs) that have resulted from ancestral infections by exogenous retroviruses. ERVs are germline encoded, transmitted in a Mendelian fashion and account for about 8% of the human and 9.9% of the murine genome, respectively1, 2. By spontaneous activation and reintegration ERVs may cause insertional mutagenesis and thus participate in the process of malignant transformation or progression of tumor growth3, 4. However, if the innate immune system is able to recognize and control ERVs has not yet been elucidated. Here we report that, in vitro, nucleic-acid sensing TLRs on dendritic cells are activated by retroviral RNA and DNA from infected cells in vitro. Infection of TLR competent wild type mice with murine leukemia virus (MuLV)-like ERV isolates results in non-canonical gene upregulation, independent of type I IFN. In vivo, TLR3, -7 and -9 triple deficient mice (TLR379-/-) and mice with non functional TLR3, 7 and 9 signaling due to a mutation in UNC93B develop spontaneous ERV-induced viremia. More importantly, in TLR379-/- mice ERV-induced viremia correlates with acute T cell lymphoblastic leukemia (T-ALL). Multiple independent TLR379-/- T cell leukemia lines produce infectious MuLV of endogenous origin. These cell lines display de novo retroviral integration into the Nup214 or Notch1 gene locus leading to gene dysregulation that is reminiscent of aberrant Nup214 and Notch1 expression in human T-ALLs5. Overall, our results demonstrate that in addition to their role in innate immune defense against exogenous pathogens, TLR3,-7, and -9 may be essential for the control of endogenous retroviral mediated T-cell lymphomagenesis.
Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors.
Specimen part
View SamplesSeveral aspects of a Western lifestyle such as increased obesity and decreased physical activity are associated with increased risk for gastrointestinal cancers1. Although high-fat diet (HFD) induced low-grade inflammation has been closely linked to tumorigenesis2, however, the microbial shift that occurs due to diet and consequent alterations in host immunity have merely been considered to play a critical role during carcinogenesis. Here we show that HFD promotes tumor progression in the small intestine of genetically susceptible mice, however, independently of obesity and diet-induced chronic inflammation. HFD consumption cooperates with mutant K-Ras to mediate a shift in the composition of microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHCII presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized and tumor progression attenuated completely when K-Ras mutant mice are supplemented with the short chain fatty acid butyrate, a bacterial fermentation end product, or partially when provided with probiotics. Importantly, Myd88-deficiency completely blocks tumor progression in K-ras mutants, however, rather by substantial changes in the microbiota than host-mediated signaling mechanisms. Strikingly, transfer of fecal samples from diseased donors into healthy adult K-ras mutants is sufficient to enhance tumor progression in the absence of HFD suggesting a pivotal role for distinct microbiota shifts in aggravating disease in the small intestine. Collectively, these data underscore the reciprocal interaction between host and environmental factors for the composition of intestinal microbiota that favors carcinogenesis and suggest tumor progression could potentially be transmitted in genetically predisposed individuals.
No associated publication
Specimen part
View SamplesTLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production.
Improved host defense against septic peritonitis in mice lacking MyD88 and TRIF is linked to a normal interferon response.
Specimen part, Treatment
View SamplesIn this study gene expression of human blood classical monocytes (CD14++CD16-), CD16 positive monocytes (consisting of non-classical CD14+16++ and intermediate CD14++CD16+ monocytes) and CD1c+ CD19- dendritic cells from healthy subjects were investigated.
Transcript profiling of CD16-positive monocytes reveals a unique molecular fingerprint.
Specimen part
View SamplesIn 20% of IRF4 deficient mice older than 150 days, spontaneous highly malignant pre B cell lymphomas emerge. A change in the expression profile of genes involved in tumor progession and malignancy is sought for by microarray analyses.
No associated publication
Specimen part
View Samples