Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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Not AvailableKrishi Vigyan Kendra, Bhadohi conducted 124 demonstrations on mustard variety - NRCHB-101, ND-8501, Pusa- Jagannath and Pusa –Vijai during two consecutive years from 2013–14 to 2014–15. The critical inputs were identified in existing production technology through meetings and discussions with farmers. Delayed sowing, use of higher seed rate resulting into dense plant population, uneven plant population, uncontrolled weeds, ignorance about fertilizers and lack of plant protection measures were the predominant identified causes of low productivity of oilseeds in district Bhadohi. In the same sequence the other parameters like technological impact, economical impact and extension gap were analyzed for Impact assessment of front line demonstration on mustard crop and feasibility of demonstrated technologies at grass root levels. The results of two years study revealed that the yield under demonstration plots was 21.50 q /ha as compared to 16.65 q /ha in traditional farmer practices plots. This additional yield of 4.85 q /ha and the increase in average mustard productivity by 29.13 per cent may contribute to present oilseed requirement on national basis. The average of technology gap, extension gap and technology index were found to be 9.27 q /ha, 3.05 q/ha and 34.63 per cent respectively. The results clearly indicate the positive effects of FLDs over the existing practices. Benefit: cost ratio was recorded to be higher under demonstrations against control treatments during the years of experimentation.Not Availabl

Polyester nanomedicines targeting inflammatory signaling pathways for cancer therapy

Funding Information: The work is funded from SRG grant (Grant no. SRG/2022/000395 ) by Science and Engineering Research Board, Department of Science and Technology , Govt. of India. Publisher Copyright: © 2022 The AuthorsThe growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-β), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving thephysicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer.Peer reviewe