Zobrazení zdroje stránky Soliselgaard1132

Low culture temperature is known to enhance the cell-specific productivity of CHO cells expressing varied recombinant (r-) proteins, but the mechanisms remain unclear. Regulation of UPR pathway genes, such as transcriptional regulatory factors and ER-resident proteins, appear to be involved in the improvements of r-protein production under low temperature conditions. We studied the transcriptional regulation of UPR-specific targets in response to decreased culture temperature in relation to production of a difficult-to-express (DTE) protein. A clonally-derived CHO cell line expressing a chimeric fusion protein (human EPO linked to a murine Fc region, hEPO-Fc) was evaluated in terms of growth, metabolism, r-protein production and UPR-/ERAD-specific gene expression at standard (37&nbsp;°C) and low (32&nbsp;°C) temperature in batch and fed-batch systems. Low temperature decreased peak cell density, improved viability, generated cell cycle arrest in the G1 phase and enhanced hEPO-Fc expression in both batch and fed-batch cultures. A low culture temperature significantly upregulated genes encoding UPR-specific transcriptional activators (xbp1s, ddit3 and atf5) and ER-resident proteins (grp78, grp94, trib3, and ero1α), that are associated with folding and processing of proteins within the ER. Further, low culture temperature decreased expression of genes involved in ERAD (edem3, sels, herpud1 and syvn1) indicating a decreased potential for protein degradation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.SCOPE Abdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, high cholesterol and glucose concentrations can be reduced by a healthier lifestyle. Hence, our aim is to understand the relation between lifestyle-induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers. METHODS AND RESULTS We used the data from the Growing Old Together (GOTO) study, which is a single arm lifestyle intervention in which 164 older adults (mean age 63 years, BMI 23-35 kg/m2 ) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. We show that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. Next, we show that the applied lifestyle intervention mainly reduces abdominal fat mass (-2.6%, SD = 3.0) and that this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter. CONCLUSIONS The lifestyle-induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with decreased circulating glycerol concentrations and increased HDL diameter. [https://www.selleckchem.com/products/ca3.html click here] This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Realist methodologies have been increasingly advocated for the investigation of complex social issues. Public health programs, such as those designed to prevent adolescent risk behavior, are typically considered complex. In conducting a realist review of the empirical literature relating to such programs, we encountered several challenges, including (a) an overabundance of empirical evidence, (b) a problematic level of heterogeneity within and between methodological approaches, (c) discrepancies between theoretical underpinnings and program operationalization, (d) homogeneity of program outcomes, with very little variation in program effectiveness, and (d) a paucity of description relating to content and process. To overcome these challenges, we developed a customized approach to realist evidence synthesis, drawing on the VICTORE (Volition, Implementation, Contexts, Time, Outcomes, Rivalry, and Emergence) complexity checklist and incorporating stakeholder engagement as primary data to achieve greater depth ofese are not recommended to be used in a prescriptive sense, and customization of the methodology to account for potential idiosyncrasies within a specific evidence base is accepted. A small number of papers within the existing literature have used each of the two key adaptions discussed within this study, though reasons for doing so have not been considered in any great depth. Furthermore, combining both of these adaptions to take an evaluative approach to realist synthesis is novel to this work and lends greater ontological depth to the research findings than may otherwise have been achieved. This study builds on key methodological developments in realist research, demonstrating how realist methodologies can be customized to overcome challenges in developing and refining program theory from the literature, and contributes to the broader literature of innovative approaches to realist research. © 2020 The Authors. Research Synthesis Methods published by John Wiley &amp; Sons Ltd.OBJECTIVE Emotional distress, including depression and anxiety, is commonly reported amongst individuals experiencing psychosis. The beliefs individuals hold about the meaning of their psychosis may explain the distress they experience. The current meta-analysis aimed to review the association between beliefs about psychosis experiences and emotional distress. METHOD Three electronic databases (PsycINFO, MEDLINE, and CINAHL) were searched using keywords and controlled vocabulary (e.g., Medical Subject Headings) from date of inception to August 2019. A total of 19 eligible papers were identified. RESULTS Our random-effects meta-analysis revealed that depression and anxiety held moderate association with psychosis beliefs, with perceptions concerning a lack of control over experiences having the strongest association with distress. Longitudinal studies suggest that negative beliefs at baseline are associated with depressive symptoms at follow-up. CONCLUSIONS The results suggest that the endorsement of negative beliefs about psychosis is associated with current level of depression and anxiety.