Frequency associated with Middle Eastern Breathing Malady Coronavirus in Dromedary Camels, Egypt.
  importance of metal-chelating mechanisms for the induction of this effect and support the viability of topoisomerase IIβ as an upstream druggable target for effective and clinically translatable cardioprotection. The American Society for Pharmacology and Experimental Therapeutics.OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is a common prelude to cirrhosis and hepatocellular carcinoma. The genetic rs641738 C> T variant in the lysophosphatidylinositol acyltransferase 1 (LPIAT1)/membrane bound O-acyltransferase domain-containing 7, which incorporates arachidonic acid into phosphatidylinositol (PI), is associated with the entire spectrum of NAFLD. In this study, we investigated the mechanism underlying this association in mice and cultured human hepatocytes.  https://www.selleckchem.com/products/decursin.html  DESIGN We generated the hepatocyte-specific Lpiat1 knockout mice to investigate the function of Lpiat1 in vivo. We also depleted LPIAT1 in cultured human hepatic cells using CRISPR-Cas9 systems or siRNA. The effect of LPIAT1-depletion on liver fibrosis was examined in mice fed high fat diet and in liver spheroids. Lipid species were measured using liquid chromatography-electrospray ionisation mass spectrometry. Lipid metabolism was analysed using radiolabeled glycerol or fatty acids. RESULTS The hepatocyte-specific Lpiat1 knockout mice developed hepatic steatosis spontaneously, and hepatic fibrosis on high fat diet feeding. Depletion of LPIAT1 in cultured hepatic cells and in spheroids caused triglyceride accumulation and collagen deposition. The increase in hepatocyte fat content was due to a higher triglyceride synthesis fueled by a non-canonical pathway. Indeed, reduction in the PI acyl chain remodelling caused a high PI turnover, by stimulating at the same time PI synthesis and breakdown. The degradation of PI was mediated by a phospholipase C, which produces diacylglycerol, a precursor of triglyceride. CONCLUSION We found a novel pathway fueling triglyceride synthesis in hepatocytes, by a direct metabolic flow of PI into triglycerides. Our findings provide an insight into the pathogenesis and therapeutics of NAFLD. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.BACKGROUND Ridesharing services (eg, Uber, Lyft) have facilitated over 11 billion trips worldwide since operations began in 2010, but the impacts of ridesharing on motor vehicle injury crashes are largely unknown. - METHODS This spatial ecological case-cross over used highly spatially and temporally resolved trip-level rideshare data and incident-level injury crash data for New York City (NYC) for 2017 and 2018. The space-time units of analysis were NYC taxi zone polygons partitioned into hours. For each taxi zone-hour we calculated counts of rideshare trip origins and rideshare trip destinations. Case units were taxi zone-hours in which any motor vehicle injury crash occurred, and matched control units were the same taxi zone from 1 week before (-168 hours) and 1 week after (+168 hours) the case unit. Conditional logistic regression models estimated the odds of observing a crash (separated into all injury crashes, motorist injury crashes, pedestrian injury crashes, cyclist injury crashes) relative to rideshare trip counts. Models controlled for taxi trips and other theoretically relevant covariates (eg, precipitation, holidays). RESULTS Each additional 100 rideshare trips originating within a taxi zone-hour was associated with 4.6% increased odds of observing any injury crash compared with the control taxi zone-hours (OR=1.046; 95% CI 1.032 to 1.060). Associations were detected for motorist injury and pedestrian injury crashes, but not cyclist injury crashes. Findings were substantively similar for analyses conducted using trip destinations as the exposure of interest. CONCLUSIONS Ridesharing contributes to increased injury burden due to motor vehicle crashes, particularly for motorist and pedestrian injury crashes at trip nodes. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Most analysis of road injuries examines the risk experienced by people using different modes of transport, for instance, pedestrian fatalities per-head or per-km. A small but growing field analyses the impact that the use of different transport modes has on other road users, for instance, injuries to others per-km driven. METHODS This paper moves the analysis of risk posed to others forward by comparing six different vehicular modes, separating road types (major vs minor roads in urban vs rural settings).  https://www.selleckchem.com/products/decursin.html  The comparison of risk posed by men and women for all these modes is also novel. RESULTS Per-vehicle kilometre, buses and lorries pose much the highest risk to others, while cycles pose the lowest. Motorcycles pose a substantially higher per-km risk to others than cars. The fatality risk posed by cars or vans to ORUs per km is higher in rural areas. Risk posed is generally higher on major roads, although not in the case of lorries, suggesting a link to higher speeds. Men pose higher per-km risk to others than women for all modes except buses, as well as being over-represented among users of the most dangerous vehicles. CONCLUSIONS Future research should examine more settings, adjust for spatial and temporal confounders, or examine how infrastructure or route characteristics affect risk posed to others. Although for most victims the other vehicle involved is a car, results suggest policy-makers should also seek to reduce disproportionate risks posed by the more dangerous vehicles, for instance, by discouraging motorcycling. Finally, given higher risk posed to others by men across five of six modes analysed, policy-makers should consider how to reduce persistent large gender imbalances in jobs involving driving. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Myosin is a major component of the sarcomeres of muscle, but its roles during muscle development are still relatively poorly understood. A new paper in Development investigates the function of a developmentally expressed myosin heavy chain isoform during mice myogenesis. We caught up with the paper's four co-first authors, Megha Agarwal, Akashi Sharma, Pankaj Kumar and Amit Kumar, and their supervisor Sam Mathew (Associate Professor in the Regional Centre for Biotechnology in Faridabad, India) to find out more about the project. © 2020. Published by The Company of Biologists Ltd.