In-Silico elucidation of the three-dimensional molecular structures defining the resistance mechanism by NBS-LRR proteins towards foliar blast disease elicitins in pearl millet

Abstract: Foliar blast disease caused by the fungus Magnaporthe grisea (Hebert) Barr, forms one of the worst scourge for pearl millet recently. Resistant lines recognizes molecular signature of pathogen infection (Avr gene products) and triggers downstream response signaling pathways in host plants through activation of Resistance (R) proteins, that works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study aimed at predicting three-dimensional structure of Resistance gene candidate (RGCs) protein RGPM 213 through ab-initio method of protein modeling. The structured protein models were further validated for structure and function and determine the ADP ligand binding site on the molecule through bioinformatics software. Availability of 3D structural model for NBS and other domains in RGCs will help in getting deeper insight in these pathogen defense genes, thereby manipulating them by site directed mutation or protein engineering to increase its efficacy towards the fight against pearl millet blast and other pathogens. Conference Details: 1st National Genetic Congress on Genetics for Sustainable Food, Health and Nutrition Security. ICAR-Indian Agricultural Research Institute, New Delhi.   Publication date: 2018/12/14 </p

Evolution of π0\pi^0 suppression in Au+Au collisions from sNN=39\sqrt{s_{NN}} = 39 to 200 GeV

International audienceNeutral-pion, pi^0, spectra were measured at midrapidity (|y|<0.35) in Au+Au collisions at sqrt(s_NN) = 39 and 62.4 GeV and compared to earlier measurements at 200 GeV in the 1<p_T<10 GeV/c transverse-momentum (p_T) range. The high-p_T tail is well described by a power law in all cases and the powers decrease significantly with decreasing center-of-mass energy. The change of powers is very similar to that observed in the corresponding p+p-collision spectra. The nuclear-modification factors (R_AA) show significant suppression and a distinct energy dependence at moderate p_T in central collisions. At high p_T, R_AA is similar for 62.4 and 200 GeV at all centralities. Perturbative-quantum-chromodynamics calculations that describe R_AA well at 200 GeV, fail to describe the 39 GeV data, raising the possibility that the relative importance of initial-state effects and soft processes increases at lower energies. A conclusion that the region where hard processes are dominant is reached only at higher p_T, is also supported by the x_T dependence of the x_T-scaling power-law exponent

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance