502 research outputs found

    Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy

    Get PDF
    Altered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication.Peer reviewe

    101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

    Get PDF
    Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species

    The Impact of Kaluza-Klein Excited W Boson on the Single Top at LHC and Comparison with other Models

    Full text link
    We study the s-channel single top quark production at the LHC in the context of extra dimension theories, including the Kaluza-Klein (KK) decomposition. It is shown that the presence of the first KK excitation of WW gauge boson can reduce the total cross section of s-channel single top production considerably if MWKK∼2.2TeVM_{W_{KK}}\sim2.2 \rm TeV (3.5TeV3.5 \rm TeV) for 7TeV7\rm TeV (14TeV14\rm TeV) in proton-proton collisions. Then the results will be compared with the impacts of other beyond Standard Model (SM) theories on the cross section of single top s-channel. The possibility of distinguishing different models via their effects on the production cross section of the s-channel is discussed.Comment: 23 pages,6 figure

    Radiogenic and Muon-Induced Backgrounds in the LUX Dark Matter Detector

    Get PDF
    The Large Underground Xenon (LUX) dark matter experiment aims to detect rare low-energy interactions from Weakly Interacting Massive Particles (WIMPs). The radiogenic backgrounds in the LUX detector have been measured and compared with Monte Carlo simulation. Measurements of LUX high-energy data have provided direct constraints on all background sources contributing to the background model. The expected background rate from the background model for the 85.3 day WIMP search run is (2.6±0.2stat±0.4sys)×10−3(2.6\pm0.2_{\textrm{stat}}\pm0.4_{\textrm{sys}})\times10^{-3}~events~keVee−1_{ee}^{-1}~kg−1^{-1}~day−1^{-1} in a 118~kg fiducial volume. The observed background rate is (3.6±0.4stat)×10−3(3.6\pm0.4_{\textrm{stat}})\times10^{-3}~events~keVee−1_{ee}^{-1}~kg−1^{-1}~day−1^{-1}, consistent with model projections. The expectation for the radiogenic background in a subsequent one-year run is presented.Comment: 18 pages, 12 figures / 17 images, submitted to Astropart. Phy

    Search for single vector-like quarks in ppbar collisions at sqrt(s) = 1.96 TeV

    Get PDF
    We present a search for hypothetical vector-like quarks in ppbar collisions at sqrt(s) = 1.96 TeV. The data were collected by the D0 detector at the Fermilab Tevatron Collider and correspond to an integrated luminosity of 5.4 fb^(-1). We select events with a final state composed of a W or Z boson and a jet consistent with a heavy object decay. We observe no significant excess in comparison to the background prediction and set limits on production cross sections for vector-like quarks decaying to W+jet and Z+jet. These are the most stringent mass limits for electroweak single vector-like quark production at hadron colliders.Comment: submitted to Phys. Rev. Let
    • …
    corecore