Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.
Type 2 diabetes (T2D) is associated with insulin resistance, impaired insulin secretion from the pancreatic β-cell, and nonalcoholic fatty liver disease (NAFLD). SWELL1 (LRRC8a) ablation impairs adipose and skeletal muscle insulin-pAKT2 signaling, β-cell insulin secretion and glycemic control - suggesting that SWELL1-LRRC8 complex dysfunction contributes to T2D pathogenesis. Here, we show that ICl,SWELL and SWELL1 protein are reduced in adipose and β-cells in murine and human T2D. Combining cryo-electron microscopy, molecular docking, medicinal chemistry, and functional studies, we define a structure activity relationship to rationally-designed active derivatives (SN-40X) of a SWELL1 channel inhibitor (DCPIB/SN-401), that bind the SWELL1-LRRC8 hexameric complex, restore SWELL1-LRRC8 protein, plasma membrane trafficking, signaling and islet insulin secretion via SWELL1-dependent mechanisms. In vivo, SN-401 and active SN-40X compounds restore glycemic control and prevents NAFLD by improving insulin-sensitivity and insulin secretion in murine T2D. These findings demonstrate that small molecule SWELL1 modulators restore SWELL1-dependent insulin-sensitivity and insulin secretion in T2D and may represent a first-in-class therapeutic approach for T2D and NAFLD.
Rajma (Phaseolus vulgaris L) known as the common bean, French bean, kidney bean, bush bean, and pole bean is the most important grain legume of Nepal which covers about 10,529 ha areas along with the productivity of 1477kgha-1. Generally it is grown during summer in mid/high hills and during winter (post rainy) season interai/inner terai in rice and maize based eco-system. Now Rajma bean is being popular as the cash crop in the province 3, 5 and 6 because of producing organic products and tastier quality. Multi-environment trials was carried out at Nepalgunj, Parwanipur, Itahari and Surkhet during the winter season of 2014-2017 comprised of 10 diverse Rajma genotypes in Randomized Complete Block Design with three replications in order to evaluate the quantitative variation with respect to yield and yield contributing traits. The combined analysis of variance showed that the highly significant differences among the genotypes and locations in the traits like days to flowering, days to maturity, plant height, hundred seed weight and grain yield. However; there was not any GxE interaction effect found in days to flowering, days to maturity and grain yield. Mean yield performances showed that the genotype PDR-14 (2341kgha-1) produced the highest yield followed by Utkarsh (2332kgha-1) and Arun-2 (2021kgha-1). In conclusion, PDR-14 gave 9-56% higher yield among the genotypes and its stability analysis test also indicated that PDR-14 was found a highly stable across the environments and over the years. Variegated red kidney shape seed, white flowers along with dwarf and glabrous leaf pubescence is the DUS trait of the PDR-14 and recommended for terai/inner terai to high hills.
23Insulin secretion from the pancreatic β-cell is initiated by activation of voltage-gated Ca 2+ channels 24(VGCC) to trigger Ca 2+ -mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of 25VGCC depends on the β-cell membrane potential, which is in turn mediated by the balance of 26 depolarizing (excitatory) and hyperpolarizing (inhibitory) ionic currents 1-3 . While much attention has 27 focused on inhibitory potassium currents 4-10 there is little knowledge about the excitatory currents 28 required to depolarize the β-cell, including the molecular identity of these excitatory currents 3 . Here we
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