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PROVIDER: PRJEB59726 | ENA |
REPOSITORIES: ENA
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Project description:In vivo and in vitro microbiota responses to three prebiotics
| PRJEB52378 | ENA
Project description:Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deletion of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived IL-22 production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings demonstrate that Ffar2 regulates colonic ILC3 proliferation and function in a cell-intrinsic manner and identifies an ILC3-receptor signaling pathway regulating gut inflammatory tone and pathogen defense.
2019-09-16 | GSE137508 | GEO
Project description:Type I Protein Arginine Methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginine (ADMA) residues on numerous protein substrates to modulate their activity. Type I PRMTs and many of their substrates have been implicated in human cancers, suggesting that inhibiting Type I PRMT activity offers a tractable approach for therapeutic intervention. The current report describes GSK3368715 (EPZ019997), a potent, reversible Type I PRMT inhibitor with anti-tumor activity against human cancer cells both in vitro and in vivo. GSK3368715 reduces ADMA on numerous substrates and concomitantly increases monomethyl (MMA) and symmetric dimethyl arginine (SDMA) levels. Inhibition of PRMT5, the major type II PRMT, attenuates this induction and produces synergistic antiproliferative effects in combination with GSK3368715 in cancer cells. PRMT5 activity is inhibited by 2-methylthioadenosine (MTA), a naturally occurring metabolite that accumulates in tumor cells deficient for the enzyme Methylthioadenosine Phosphorylase (MTAP). MTAP deletion in cancer cell lines correlates with sensitivity to GSK3368715, indicating a sufficient degree of PRMT5 inhibition from MTA accumulation to achieve a tumor cell-intrinsic combination. These data provide the rationale to explore MTAP status as a biomarker strategy for patient selection to maximize the anti-tumor activity of GSK3368715.
2019-08-15 | GSE126651 | GEO
Project description:Low pH-induced alterations in gene expression profiles and organic acids (OAs) and free amino acids (FAAs) abundances were investigated in Citrus sinensis leaves. We identified 503 downreg-ulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OAs biosyn-thesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen com-pounds, proteins and FAAs in leaves, which might be conducive to maintaining energy homeo-stasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses, in-cluding phosphate recycling, lipid remodeling and phosphate transport. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid and pyroglutamic acid), but it impaired pentose phosphate pathway, VE and secondary metabolite biosynthesis, downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase and 2-alkenal re-ductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.
2018-05-12 | GSE114369 | GEO
Project description:Salmonella enteritidis is suggested to translocate in the small intestine. Previously we identified that prebiotics, fermented in the colon, increased Salmonella translocation in rats, suggesting involvement of the colon in translocation. Effects of Salmonella on colonic gene expression in vivo are largely unknown. The aim of this study was to characterize time dependent Salmonella induced changes of colonic mucosal gene expression in rats using whole genome microarrays. Rats were orally infected with Salmonella enteritidis to mimic a foodbore infection and colonic gene expression was determined at day 1, 3 and 6 post-infection (n=8 per timepoint). Agilent rat whole genome microarray (G4131A Agilent Technologies) were used. Results indicate that colon is clearly a target tissue for Salmonella considering the abundant changes in mucosal gene expression observed. Keywords: Time point infection study, colon mucosa, Rat
2007-10-18 | GSE7496 | GEO
Project description:Microbial EPS production from various substrates
| PRJEB39763 | ENA