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Rossi Hoover posted an update 1 day, 1 hour ago
Eukaryotic cells take up macromolecules and particles from the surrounding milieu and also internalize membrane proteins via a precise process of endocytosis. The role of endocytosis in diverse physiological processes such as cell adhesion, cell signaling, tissue remodeling, and healing is well recognized. The epithelial tight junctions (TJs), present at the apical lateral membrane, play a key role in cell adhesion and regulation of paracellular pathway. These vital functions of the TJ are achieved through the dynamic regulation of the presence of pore and barrier-forming proteins within the TJ complex on the plasma membrane. In response to various intracellular and extracellular clues, the TJ complexes are actively regulated by intracellular trafficking. The intracellular trafficking consists of endocytosis and recycling cargos to the plasma membrane or targeting them to the lysosomes for degradation. Increased intestinal TJ permeability is a pathological factor in inflammatory bowel disease (IBD), and the TJ permeability could be increased due to the altered endocytosis or recycling of TJ proteins. This review discusses the current information on endocytosis of intestinal epithelial TJ proteins. The knowledge of the endocytic regulation of the epithelial TJ barrier will provide further understanding of pathogenesis and potential targets for IBD and a wide variety of human disease conditions.Forty pigs [10.7 ± 1.2 kg initial body weight (BW) at 6 wk of age] were used in a 21-d study to evaluate the effects of supplemental xylanase (Hostazym X 100, Huvepharma, Inc., Peachtree City, GA) in nursery diets on digesta viscosity, nutrient digestibility, health of the small intestine, and growth performance when supplemented with corn distillers’ dried grains with solubles (DDGS). Pigs were individually housed and randomly allotted to four treatments in a 2 × 2 factorial arrangement (n = 20/factor, 0% or 30% DDGS and 0 or 1,500 endo-pentosanase unit/kg xylanase as two factors) based on sex and initial BW. Feed intake and BW were recorded weekly. On day 15 of the study, TiO2 in diets (0.3%) was used as an indigestible marker to calculate apparent ileal digestibility (AID). Plasma samples were collected on day 19 to measure tumor necrosis factor-alpha (TNF-α), malondialdehyde, and peptide YY. On day 21, all pigs were euthanized to collect tissues from duodenum, jejunum, and colon to measure morphology, TNFP less then 0.05) villus heightcrypt depth ratio (1.46 to 1.27), whereas supplemental xylanase increased (P less then 0.05) the crypt depth (360 to 404 µm) in duodenum. In conclusion, feeding a diet with 30% DDGS to nursery pigs for 3 wk had no negative effect on growth performance, whereas reduced AID of DM and GE, increased TNF-α level in colon tissue, and reduced the ratio of villus height to crypt depth. Dietary supplementation of xylanase reduced digesta viscosity improving AID of nutrients, reduced inflammatory response, and altered intestinal morphology, collectively improving ADG of nursery pigs regardless of the use of DDGS in a diet.Background Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and test whether affected patients were genetically predisposed to multiple sclerosis (MS). Methods We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF. We compared genetic risk scores (GRS), calculated using carriage of 43 susceptibility loci for MS, in 48 cases to 1219 patients exposed to anti-TNF who did not develop demyelination. Results Overall, 39 (74%) cases were female. The median age (range) of patients at time of demyelination was 41.5 years (20.7 – 63.2). The median duration of anti-TNF treatment was 21.3 months (0.5 – 99.4) and 19 (36%) patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord or both. Complete recovery was reported in 12 (23%) patients after a median time of 6.8 months (0.1 – 28.7). After 33.0 months of follow-up partial recovery was observed in 29 (55%) patients, relapsing and remitting episodes in 9 (17%), progressive symptoms in 3 (6%) 2 (4%) patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 x 10-4, SD 0.0039) and controls (mean -1.1×10-3, SD 0.0042) (p=0.23). Conclusions Patients who experienced demyelination events following anti-TNF were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.We present a novel model of grass, which fully integrates shoot morphogenesis and the metabolism of carbon (C) and nitrogen (N) at organ scale, within a 3D representation of plant architecture. Plant morphogenesis is seen as a self-regulated system driven by two main mechanisms. First, the rate of organ extension and the establishment of architectural traits are regulated by concentrations of C and N metabolites in the growth zones and their temperature. Second, the timing of extension is regulated by rules coordinating successive phytomers instead of a thermal time schedule. Local concentrations are calculated from a model of C and N metabolism at organ scale. The 3D representation allows for accurate calculation of light and temperature distribution within the architecture. The model was calibrated for wheat (Triticum aestivum) and evaluated for early vegetative stages. Our approach allowed simulation of realistic patterns of leaf dimensions, extension dynamics, organ mass and composition. Leurocristine The model simulated, as emergent properties, plant and agronomic traits. Metabolic activities of growing leaves were investigated in relation to the whole plant functioning and environmental conditions. The current model is an important step towards a better understanding of the plasticity of the plant’s phenotype in contrasting environments.