Hatchergrimes1690

Sleep problems and circadian misalignment affect health and well-being and are highly prevalent in those with co-morbid neuropsychiatric disorders. Interventions altering light exposure patterns of affected individuals are a promising non-pharmacological treatment option, shown by previous meta-analyses to improve sleep, and often described as minimally invasive. To best translate laboratory-based mechanistic research into effective treatments, acceptability and barriers to adherence should be understood, but these have not yet been systematically evaluated. Here, we examined evidence regarding adherence and acceptability in studies of light or dark interventions using various delivery devices and protocols to improve sleep in intrinsic circadian rhythm sleep-wake disorders and neuropsychiatric illness. Attrition during intervention was low, and reported experiences were largely positive, but measurement and reporting of self-reported experiences, expectations, and adverse effects were poor. Approaches to management and measurement of adherence were varied, and available light monitoring technology appeared under-exploited, as did mobile technology to prompt or track adherence. Based on these findings we suggest recommended reporting items on acceptability and adherence for future investigations. Few studies assessed baseline light exposure patterns, and few personalised interventions. Overall, many applied studies exhibited an approach to light schedule interventions still reminiscent of laboratory protocols; this is unlikely to maximise acceptability and clinical effectiveness. For the next phase of translational research, user acceptability and adherence should receive increased attention during intervention design and study design. We suggest framing light therapies as complex interventions, and emphasise the occupationally embedded (daily activity routine embedded) context in which they occur. Porcine epidemic diarrhea virus (PEDV) causes very high mortality in newborn piglets. The mucosal immune system in the gut must eliminate potential pathogens while maintaining a mutually beneficial relationship with the commensal microbiota. Antibodies derived from the secretory immunoglobulin A (SIgA) class, act as the first line of antigen-specific immunity in the gut by recognizing both pathogens and commensals. Therefore, the measurement of SIgA levels is an important index in evaluating PEDV infections and immune status. A simple and rapid method for the detection of PEDV-specific SIgA using an immunochromatographic test strip has been developed; incorporating a colloidal gold-labeled anti-SIgA secretory component (SC) mAb probe for the detection of anti-PEDV-specific SIgA in swine. On the strip, a gold-labeled anti-SIgA SC mAb was applied to a conjugate pad; purified PEDV particles and goat anti-mouse antibodies were blotted onto a nitrocellulose membrane to form the test and control lines, respectively. Results showed that the immunochromatographic test strip had high sensitivity and specificity. When compared with enzyme-linked immunosorbent assay, kappa value suggesting that the strip could be used to detect PEDV specific SIgA in colostrum samples. Furthermore, the strip assay is rapid and easy to perform with no requirement for professional-level skills or equipment. We found that the immunochromatographic test strip was a rapid, sensitive, and reliable method for the identification of PEDV specific SIgA, indicating its suitability for epidemiological surveillance as well as vaccine immunity when studying PEDV. The adverse effects of triphenyltin (TPT) on aquatic systems have attracted much attention because TPT is widely used and prevalent in aquatic environments. Here, zebrafish embryos/larvae were exposed to TPT (0, 0.039, 0.39, and 3.9 nM; 0, 15, 150 and 1500 ng/L) for 7 or 14 days to determine its toxic effects on the hypothalamic-pituitary-thyroid (HPT) axis. The results showed that whole-body total T4 and T3 levels were significantly decreased, which was accompanied by the significant upregulation of the expression of the dio1, dio2 and ugt1ab genes after exposure to TPT for 7 and 14 days. Genes related to thyroid hormone synthesis (crh, tshβ, nis, tpo and tg) were upregulated at both 7 and 14 days after TPT exposure. This might have been due to the positive feedback regulation of the HPT axis, which is caused by a decrease in thyroid hormone in the whole body in zebrafish. In addition, the survival rates and body lengths were reduced after treatment with TPT for 7 and 14 days. This indicated that TPT caused adverse effect on the development of zebrafish embryos/larvae. In summary, the results suggested that TPT caused thyroid disruption and developmental toxicity in zebrafish larvae. Impaired lysosomal activity, which results in defective protein processing, waste accumulation, and protein aggregation, is implicated in a number of disease pathologies. Acidification of lysosomes is a crucial process required for lysosome function. Previously we showed that inhibition of glycogen synthase kinase-3 (GSK-3) enhanced lysosomal acidification in both normal and pathological conditions. However, how GSK-3 integrates into the lysosome networking is unknown. Here we show that inhibition of mTORC1 and increased autophagic activity are downstream to GSK-3 inhibition and contribute to lysosomal acidification. Strikingly, lysosomal acidification is also restored by GSK-3 inhibition in the absence of functional autophagy, and, independently of mTORC1. This is facilitated by increased endocytic traffic We show that GSK-3 inhibition enhanced material internalization, increased recruitment of active Rab5 into endosomes, and increased Rab7/RILP clustering into lysosomes, all processes required for late endosome maturation. Consistently, in cells defective in endocytic traffic caused by either constitutively active Rab5, or, deletion of the Niemann-Pick C1 protein, GSK-3 inhibition could not restore lysosomal acidification. SU056 ic50 Finally we found that the tuberous sclerosis complex, TSC, is required for lysosomal acidification and is activated by GSK-3 inhibition. Thus, the GSK-3/TSC axis regulates lysosomal acidification via both the autophagic and endocytic pathways. Our study provides new insights into the therapeutic potential of GSK-3 inhibitors in treating pathological conditions associated with impaired cellular clearance.