Beebe Coughlin (guidegarden24)

geographic price variation. Master CD4+ T cell lineage determined transcription factors are found to be dysregulated in pathogenesis of autoimmune and inflammatory diseases. CD4+ T cells categorized into different lineages based on their functions, cell surface markers and master transcription factors those required for expression of lineage specific cytokines. T-bet, GATA3, RORγt and Foxp3 are major transcription regulators of Th1, Th2, Th17 and Treg cells respectively. Significant progress has been made in understanding expression of lineage specific master regulators that drives CD4+ T cell differentiation. It is known that each CD4+ T cell lineage express precise determined transcription factor and due to cross regulation between these factors the CD4+ T cells able to maintain thier specific phenotype. However, recent studies shows that the lineage specifying transcription factors frequently co-expressed. There is an emerging area of research revealing that the co-expression of lineage-specifying transcription factors alters the potential function and flexibility of subsets of CD4+ T cell, this in turn favors the autoimmune pathology. Here, we discuss similarities and differences between mutually co-expressed transcription factors in CD4+ T cell subsets and then recapitulates on cell type specific and dynamic balance between the lineage restricted transcription factors in determining plasticity of CD4+ T cell subsets. Furthermore, we discuss abnormal regulation of such transcription factors that establishes a pathogenic CD4+ T cell phenotype in autoimmune diseases and how this understanding will provide further insight into potential therapeutic development. Biotin, thiamine, and lipoic acid are industrially important molecules naturally synthesized by microorganisms via biosynthetic pathways requiring iron-sulfur (FeS) clusters. Current production is exclusively by chemistry because pathway complexity hinders development of fermentation processes. For biotin, the main bottleneck is biotin synthase, BioB, a S-adenosyl methionine-dependent radical enzyme that converts dethiobiotin (DTB) to biotin. BioB overexpression is toxic, though the mechanism remains unclear. We identified single mutations in the global regulator IscR that substantially improve cellular tolerance to BioB overexpression, increasing Escherichia coli DTB-to-biotin biocatalysis by more than 2.2-fold. Based on proteomics and targeted overexpression of FeS-cluster biosynthesis genes, FeS-cluster depletion is the main reason for toxicity. We demonstrate that IscR mutations significantly affect cell viability and improve cell factories for de novo biosynthesis of thiamine by 1.3-fold and lipoic acid by 1.8-fold. We illuminate a novel engineering target for enhancing biosynthesis of complex FeS-cluster-dependent molecules, paving the way for industrial fermentation processes. BACKGROUND & AIMS In patients with inflammatory bowel diseases (IBD), symptoms do not always associate with the severity of endoscopic inflammation and can persist after mucosal healing. We investigated whether symptoms in patients with successfully treated IBD are related to composition of the intestinal microbiome. read more METHODS We analyzed 590 tissue biopsies from 215 patients with IBD and 48 healthy individuals (controls). We obtained mucosal biopsies from 2 colon sites (ascending and rectosigmoid) and from the terminal ileum along with clinical data. Bacterial DNA was extracted from the biopsies and the V4 region of 16s rRNA sequenced by Miseq and processed using the QIIME v1.9 pipeline. RESULTS Mucosal biopsies from patients with Crohn's disease (CD) who achieved mucosal healing (Mayo scores of 0-1 or SES-CD scores of 0-5) had lower Chao1 diversity than biopsies from patients with ulcerative colitis (UC) or unclassified IBD (IBD-U), or controls. After endoscopic evidence of improvement in patients with UC or ao1 diversity and greater dysbiosis in intestinal microbiota of