Project description:We previously reported that skeletal muscle adaptation to regular exercise requires a healthy gut microbiome, contributing to growing evidence that some exercise benefits are mediated by microbiome-derived metabolites. Here, to identify such exercise-associated microbial metabolites, we transfer cecal contents from exercise-trained donor mice into exercise-naïve recipient mice undergoing unilateral hindlimb immobilization. Recipients of cecal material from exercise-trained donors exhibit less muscle atrophy compared with those receiving transfers from sedentary donors. Untargeted metabolomics reveal metabolites enriched in cecal content, serum, and muscle of recipients from exercise-trained donors, consistent with microbial origin. Oral administration of two such metabolites (pipecolic acid and succinate) attenuates muscle atrophy and preserves muscle function in exercise-naïve mice, potentially by enhancing cellular energy status and translational capacity. These findings further define the gut microbiome-skeletal muscle axis and provide evidence that exercise-associated microbial metabolites serve as a novel class of exercise mimetics for treating conditions responsive to physical activity.
Project description:We have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from whole virus produced in Vero cells.
Project description:In order to determine whether dis-regulation of a genetic pathway could explain the increased apoptosis of parp-2-/- double positive thymocytes, the gene expression profiles in double positive thymocytes derived from wild-type and parp-2-/- mice were analysed using Affymetrix oligonucleotide chips (mouse genome 430 2.0).
Project description:In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem /progenitor cells at their base. We found that the presence of this structure was supported by the physiologic role of a prominent bacterial metabolite, butyrate. This bacterially-produced short chain fatty acid inhibited intestinal epithelial proliferation at physiologic concentrations. During homeostasis, butyrate did not suppress epithelial stem proliferation because it was metabolized by differentiated colonocytes. Provision of butyrate access to stem/progenitor cells either through mucosal injury or application to a crypt-less host led to inhibition of proliferation. The mechanism was dependent on HDAC inhibition in stem cells and the transcription factor Foxo3. Thus, the mammalian crypt unit structure provides energy for differentiated cells at a distance from the crypt base and this action prevents suppression of stem/progenitor proliferation. In total 4 samples were analyzed from 2 independent experiments. Two samples of colonic stem cells treated with 1mM Butyrate and two samples of colonic stem cells treated with 1mM NaCl (mock) as a control
Project description:In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem /progenitor cells at their base. We found that the presence of this structure was supported by the physiologic role of a prominent bacterial metabolite, butyrate. This bacterially-produced short chain fatty acid inhibited intestinal epithelial proliferation at physiologic concentrations. During homeostasis, butyrate did not suppress epithelial stem proliferation because it was metabolized by differentiated colonocytes. Provision of butyrate access to stem/progenitor cells either through mucosal injury or application to a crypt-less host led to inhibition of proliferation. The mechanism was dependent on HDAC inhibition in stem cells and the transcription factor Foxo3. Thus, the mammalian crypt unit structure provides energy for differentiated cells at a distance from the crypt base and this action prevents suppression of stem/progenitor proliferation.
Project description:Feces samples from pigs with two different diets were analysed. Proteins from the microbiota was extracted and analysed by LC-MS/MS. Differences along the time and between the diets were observed.
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. MicroRNAs are small nucleatides that function as regulators of gene expression in almost any biological process. However, few microRNAs are reported to have a role in the pathological process of OPLL. Therefore, we performed high-throughput microRNA sequencing and transcriptome sequencing of primary OPLL and PLL cells in order to decipher the interacting network of microRNAs in OPLL. MRNA and microRNA profiles were done using primary culture cells of human ossification of the posterior longitudinal ligament (OPLL) tissue and normal posterior longitudinal ligament (PLL) tissue.
Project description:the commensal gut microbiota modulates multiple sclerosis with unknown mechanisms. Commensal bacteria producing bile acid-deconjugating enzymes are fundamental to generate secondary bile acid metabolites (BAM) with immunoregulatory function. We show that immune regulatory BAM prevent autoimmunity in the central nervous system by inducing immune tolerance at the intestinal level and peripherally limiting effector function and aggressiveness of myelin-reactive T cells. We validated the key role of microbiota-induced BAM in humans by showing that relapsing-remitting multiple sclerosis patients have significantly reduced level of an important immune regulatory BAM (deoxycholic acid) and lower abundance of BAM-producing bacteria that correlate with increased percentages of peripheral effector Th17 cells. Our data indicate that the immune regulatory biliary network is crucial for the prevention of central nervous system autoimmunity.
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM). mRNA profiles of Primary human posterior longitudinal ligament cells stimulated with various stimuli (Control, 1µM AGE-BSA, 5µM AGE-BSA, 1µM AGE-BSA with BMP2, 5µM AGE-BSA with BMP2) were generated by deep sequencing on Ion Proton