Resource profile and user guide of the Polygenic Index Repository

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies — some not previously published — from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available

Cerebral gene expression in response to single or combined gestational exposure to methylmercury and selenium through the maternal diet

Controversy remains regarding the safety of consuming certain types of seafood, particularly during pregnancy. While seafood is rich in vital nutrients, it may also be an important source of environmental contaminants such as methylmercury (MeHg). Selenium (Se) is one essential element present in seafood, hypothesised to ameliorate MeHg toxicity. The aim of the present study was to ascertain the impact of Se on MeHg-induced cerebral gene expression in a mammalian model. Microarray analysis was performed on brain tissue from 15-day-old mice that had been exposed to MeHg throughout development via the maternal diet. The results from the microarray analysis were validated using qPCR. The exposure groups included: MeHg alone (2.6 mg kg−1), Se alone (1.3 mg kg−1), and MeHg + Se. MeHg was presented in a cysteinate form, and Se as Se–methionine, one of the elemental species occurring naturally in seafood. Eight genes responded to Se exposure alone, five were specific to MeHg, and 63 were regulated under the concurrent exposure of MeHg and Se. Significantly enriched functional classes relating to the immune system and cell adhesion were identified, highlighting potential ameliorating mechanisms of Se on MeHg toxicity. Key developmental genes, such as Wnt3 and Sparcl1, were also identified as putative ameliorative targets. This study, utilising environmentally realistic forms of toxicants, delivered through the natural route of exposure, in association with the power of transcriptomics, highlights significant novel information regarding putative pathways of selenium and MeHg interaction in the mammalian brain

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

PORT FLOW SIMULATION OF AN IC ENGINE

This paper deals with the numerical analysis of 3d model which has inlet port diameter 46mm, valve diameter 43mm and the length and diameter of the cylinder is 562mm and 93.65mm respectively which is developed to study the effect of valve lift on the flow of fluid inside the cylinder. For different valve lifts velocity will change inside the cylinder. Results of CFD simulation indicated that valve lift affects velocity flow field inside the cylinder. It also proved that CFD is a convenient tool for designing and optimizing the flow field in the engine

Synthesis and pharmacological evaluation of 1,3,4-oxadiazole bearing bis(heterocycle) derivatives as anti-inflammatory and analgesic agents

A series of novel ether-linked bis(heterocycle)s have been synthesized via 3 + 2]-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition reaction of nitrite imine with carbonyl group. All the newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Among the list of compounds (7a-k) studied, 7d, 7g, 7j, and 7k exhibited excellent activity comparable to ibuprofen and aspirin at the similar dosages. (C) 2009 Elsevier Masson SAS. All rights reserved

Microsatellite based genetic diversity study in indigenous chicken ecotypes of Karnataka

Aim: The current study was the first of its kind taken upon indigenous ecotypes of the Karnataka in order to unravel the diversity details at 20 chicken microsatellite regions. Materials and Methods: 210 indigenous chicken belonging to six districts of Bangalore and Mysore division formed the target sample for the present study. The genomic deoxyribonucleic acid was isolated by phenol chloroform isoamyl alcohol method. A panel of 20 microsatellite regions, including 14 recommended by FAO and six identified from published scientific literature became the targeted chicken genomic region. 27-33 samples were successfully genotyped in each of the six ecotypes through simplex or multiplex polymerase chain reactions, polyacrylamide gel electrophoresis and silver staining for the selected microsatellite panel. Results: The chickens of Ramanagara and Chamrajnagara were most distant with a Nei’s genetic distance value of 0.22. The chickens of Bangalore rural and Mysore were least distant with a value of 0.056. The Ramanagara and Chamrajnagara pair had Nei’s genetic identity value of 0.802, which is least among all pairs of ecotypes. There were five main nodes from which the six ecotypes evolved on the basis 20 microsatellite markers used in this study. This study indicates that the four ecotypes Ramnagara, Bangalore Rural, Chickaballapura and Mysore are genetically identical due to their common ancestral evolution while, Mandya and Chamrajnagara ecotypes formed a relatively different cluster due to a separate common ancestral chicken population and less number of generations since drifting from bifurcation node. Conclusion: Twenty microsatellite markers based genetic diversity study on six indigenous ecotypes indicated lower genetic distances as well as lower FST values compared to the distinguished breeds reported. There were two main clusters, which differentiated into six ecotypes. They may differentiate into more distinct varieties if bred in isolation for a longer number of generations