SYNTHESIS, IN VITRO ANTIBACTERIAL, TOXICITY AND MOLECULAR DOCKING ANTICANCER ACTIVITY OF NOVEL N-[(2-CHLOROQUINOLIN-3-YL) METHYLIDENE]-2-ANILINE SCHIFF'S BASES

Objective: Synthesis of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) and to study their in vitro antibacterial activity and in silico study towards cancer and malarial proteins. Methods: Various N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by using 2-chloro-3-formyl quinoline and different anilines in presence of acetic acid as catalyst. All the new compounds were characterized by 1H-NMR, [13]C-NMR and LCMS analysis. The compounds 3a-j was subjected to antibacterial activity. In silico molecular properties were predicted using various online cheminformatic tools, the binding interactions with Human DNA topoisomerase I and Plasmodium falciparum lactate dehydrogenase proteins was studied through molecular docking and Irinotecan and mefloquine were used as reference drugs. Results: Fairly good yield of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by convenient and economical procedure. The preliminary in silico pharmacokinetics study reveals that the compounds 3a-j shows excellent drug like property. The toxicity profile of compounds 3a-h was found safe. The compounds 3a-j was exhibited promising MIC values against the both S. aureus and E. coli. Similarly the docking results predict that the compound 3d shown highest interaction by forming two hydrogen bonds against the cancer protein with the interaction energy-20.696 kcal/mol. Compound 3c exhibits highest dock score of-45.703 kcal/mol with two hydrogen bonds against malarial protein. Conclusion: From the results of docking studies of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j), it has been concluded that the compounds were found to exhibit multifunctional lead property, hence these compounds are worth to be considered as potential lead molecules for further study

Utilization of fungal biocontrol agents against rice sheath blight disease provides insight into their role in plant defense responses

Biotic and abiotic factors have an effect on rice production all around the world. Diseases are regarded as major restrictions among the biotic stressors, and rice sheath blight (Rhizoctonia solani Kühn) is one of the most calamitous diseases that significantly damage the crop. Lately, biocontrol of fungal plant pathogens has appeared as an appealing approach. The present investigation was undertaken to evaluate different biocontrol agents like Talaromyces flavus, Chaetomium globosum, Pseudomonas fluorescens and Aspergillus niger against sheath blight disease. Prior to sowing, seeds were bioprimed with each isolate and sown in the nursery. After 21 days, seedlings were transplanted in-vivo and were inoculated with a virulent isolate of Rhizoctonia solani at maximum tillering stage. Observations on biochemical parameters and gene expression studies were carried out at 24, 48, 72, and 96 hpi. Enzymatic activity viz., chitinase, β-1,3-glucanase, catalase, and PAL was observed  maximum in Chaetomium globosum. PR-genes viz., IPT, BrD, HmPr, AMP, AldD, NIC and LisH showed up-regulation at 96 hpi. Chaetomium globosum had the highest yield, maximum number of tillers with least RLH% as compared to other treatments. However, results indicated biocontrol agents are helpful and they induce multitude of defence responses against R. solani in rice

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

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Not AvailableField experiments were conducted in the farmers’ field at Gutthikatte village, Hosadurga taluk, Chitradurga district of Karnataka during 2015-16 and 2016-17 to study the direct and residual effect of zinc and boron on yield and yield attributes of finger millet – groundnut cropping system in zinc and boron deficient soil. The finger millet was the test crop to study the direct effect and groundnut crop was raised to study the residual effect. The experiments were laid out in Randomized Complete Block Design with fifteen treatments and replicated thrice. The pooled analysis revealed that significantly higher yield and yield attributes of finger millet and succeeding groundnut crops were recorded with the application of NPK (100:50:50 kg ha-1) + FYM (10 t ha-1) + ZnSO4 @ 15 kg ha-1 + Borax @ 12.5 kg ha-1 and residual effect of NPK + FYM + ZnSO4 @ 20 kg ha-1 + Borax @ 12.5 kg ha-1 compare to other treatments.Not Availabl

Not Available

Not AvailableField experiments were conducted in the farmers’ field at Gutthikatte village, Hosadurga taluk, Chitradurga district of Karnataka during 2015-16 and 2016-17 to study the direct and residual effect of zinc and boron on yield and yield attributes of finger millet – groundnut cropping system in zinc and boron deficient soil. The finger millet was the test crop to study the direct effect and groundnut crop was raised to study the residual effect. The experiments were laid out in Randomized Complete Block Design with fifteen treatments and replicated thrice. The pooled analysis revealed that significantly higher yield and yield attributes of finger millet and succeeding groundnut crops were recorded with the application of NPK (100 :50:50 kg/ ha) + FYM (10 t/ ha) + ZnSO4 @ 15 kg/ ha+ Borax @ 12.5 kg/ha and residual effect of NPK + FYM + ZnSO4 @ 20 kg/ha+ Borax @ 12.5 kg/ha compare to other treatments.Not Availabl