15 research outputs found
Remote marine protected area reveals unusual social behaviour in Chaetodon trifascialis
Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biodiversity 48 (2018): 155-156, doi:10.1007/s12526-016-0531-0.The research expedition was funded by New England Aquarium, Woods Hole Oceanographic Institution and King
Abdullah University of Science and Technology
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Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus
AbstractMany individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte–endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.</jats:p
48 Primocolonizing Escherichia coli Impact Colonic Epithelial Homeostasis in Gnotobiotic Rats
High-fat diet modifies the PPAR-Îł pathway leading to disruption of microbial and physiological ecosystem in murine small intestine
Early colonizing [i]Escherichia coli[/i] elicits remodeling of rat colonic epithelium shifting toward a new homeostatic state
We investigated the effects of early colonizing bacteria on the colonic epithelium. We isolated dominant bacteria, Escherichia coli, Enterococcus faecalis, Lactobacillus intestinalis, Clostridiuminnocuum and a novel Fusobacterium spp., from the intestinal contents of conventional suckling rats and transferred them in different combinations into germfree (GF) adult rats. Animals were investigated after various times up to 21 days. Proliferative cell markers (Ki67, proliferating cell nuclear antigen, phospho-histone H3, cyclin A) were higher in rats monocolonized with E. coli than in GF at all time points, but not in rats monocolonized with E. faecalis. The mucin content of goblet cells declined shortly after E. coli administration whereas the mucus layer doubled in thickness. Fluorescence in situ hybridization analyses revealed that E. coli resides in this mucus layer. The epithelial mucin content progressively returned to baseline, following an increase in KLF4 and in the cell cycle arrest-related proteins p21(CIP1) and p27(KIP1). Markers of colonic differentiated cells involved in electrolyte (carbonic anhydrase II and slc26A3) and water (aquaglyceroporin3 (aqp3)) transport, and secretory responses to carbachol were modulated after E. coli inoculation suggesting that ion transport dynamics were also affected. The colonic responses to simplified microbiotas differed substantially according to whether or not E. coli was combined with the other four bacteria. Thus, proliferation markers increased substantially when E. coli was in the mix, but very much less when it was absent. This work demonstrates that a pioneer strain of E. coli elicits sequential epithelial remodeling affecting the structure, mucus layer and ionic movements and suggests this can result in a microbiota-compliant state