701 research outputs found

    Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

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    This paper presents measurements of the W+μ+νW^+ \rightarrow \mu^+\nu and WμνW^- \rightarrow \mu^-\nu cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

    Molecular basis of sugar recognition by collectin-K1 and the effects of mutations associated with 3MC syndrome

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    Background Collectin-K1 (CL-K1, or CL-11) is a multifunctional Ca2+-dependent lectin with roles in innate immunity, apoptosis and embryogenesis. It binds to carbohydrates on pathogens to activate the lectin pathway of complement and together with its associated serine protease MASP-3 serves as a guidance cue for neural crest development. High serum levels are associated with disseminated intravascular coagulation, where spontaneous clotting can lead to multiple organ failure. Autosomal mutations in the CL-K1 or MASP-3 genes cause a developmental disorder called 3MC (Carnevale, Mingarelli, Malpuech and Michels) syndrome, characterised by facial, genital, renal and limb abnormalities. One of these mutations (Gly204Ser in the CL-K1 gene) is associated with undetectable levels of protein in the serum of affected individuals. Results In this study, we show that CL-K1 primarily targets a subset of high-mannose oligosaccharides present on both self- and non-self structures, and provide the structural basis for its ligand specificity. We also demonstrate that three disease-associated mutations prevent secretion of CL-K1 from mammalian cells, accounting for the protein deficiency observed in patients. Interestingly, none of the mutations prevent folding nor oligomerization of recombinant fragments containing the mutations in vitro. Instead, they prevent Ca2+ binding by the carbohydrate-recognition domains of CL-K1. We propose that failure to bind Ca2+ during biosynthesis leads to structural defects that prevent secretion of CL-K1, thus providing a molecular explanation of the genetic disorder. Conclusions We have established the sugar specificity of CL-K1 and demonstrated that it targets high-mannose oligosaccharides on self- and non-self structures via an extended binding site which recognises the terminal two mannose residues of the carbohydrate ligand. We have also shown that mutations associated with a rare developmental disorder called 3MC syndrome prevent the secretion of CL-K1, probably as a result of structural defects caused by disruption of Ca2+ binding during biosynthesis

    Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy

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    Leukoencephalopathies are a group of white matter disorders related to abnormal formation, maintenance, and turnover of myelin in the central nervous system. These disorders of the brain are categorized according to neuroradiological and pathophysiological criteria. Herein, we have identified a unique form of leukoencephalopathy in seven patients presenting at ages 2 to 4 months with progressive microcephaly, spastic quadriparesis, and global developmental delay. Clinical, metabolic, and imaging characterization of seven patients followed by homozygosity mapping and linkage analysis were performed. Next generation sequencing, bioinformatics, and segregation analyses followed, to determine a loss of function sequence variation in the phospholipase A2-activating protein encoding gene (PLAA). Expression and functional studies of the encoded protein were performed and included measurement of prostaglandin E2 and cytosolic phospholipase A2 activity in membrane fractions of fibroblasts derived from patients and healthy controls. Plaa-null mice were generated and prostaglandin E2 levels were measured in different tissues. The novel phenotype of our patients segregated with a homozygous loss-of-function sequence variant, causing the substitution of leucine at position 752 to phenylalanine, in PLAA, which causes disruption of the protein's ability to induce prostaglandin E2 and cytosolic phospholipase A2 synthesis in patients' fibroblasts. Plaa-null mice were perinatal lethal with reduced brain levels of prostaglandin E2 The non-functional phospholipase A2-activating protein and the associated neurological phenotype, reported herein for the first time, join other complex phospholipid defects that cause leukoencephalopathies in humans, emphasizing the importance of this axis in white matter development and maintenance

    Molecular Evolution of Regulatory Genes in Spruces from Different Species and Continents: Heterogeneous Patterns of Linkage Disequilibrium and Selection but Correlated Recent Demographic Changes

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    Genes involved in transcription regulation may represent valuable targets in association genetics studies because of their key roles in plant development and potential selection at the molecular level. Selection and demographic signatures at the sequence level were investigated for five regulatory genes belonging to the knox-I family (KN1, KN2, KN3, KN4) and the HD-Zip III family (HB-3) in three Picea species affected by post-glacial recolonization in North America and Europe. To disentangle neutral and selective forces and estimate linkage disequilibrium (LD) on a gene basis, complete or nearly complete gene sequences were analysed. Nucleotide variation within species, haplotype structure, LD, and neutrality tests, in addition to coalescent simulations based on Tajima’s D and Fay and Wu’s H, were estimated. Nucleotide diversity was generally low in all species (average π = 0.002–0.003) and much heterogeneity was seen in LD and selection signatures among genes and species. Most of the genes harboured an excess of both rare and frequent alleles in the three species. Simulations showed that this excess was significantly higher than that expected under neutrality and a bottleneck during the Last Glacial Maximum followed by population expansion at the Pleistocene/Holocene boundary or shortly after best explains the correlated sequence patterns. These results indicate that despite recent large demographic changes in the three boreal species from two continents, species-specific selection signatures could still be detected from the analysis of nearly complete regulatory gene sequences. Such different signatures indicate differential subfunctionalization of gene family members in the three congeneric species

    Evolution of Genome Size and Complexity in Pinus

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    BACKGROUND: Genome evolution in the gymnosperm lineage of seed plants has given rise to many of the most complex and largest plant genomes, however the elements involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Gymny is a previously undescribed retrotransposon family in Pinus that is related to Athila elements in Arabidopsis. Gymny elements are dispersed throughout the modern Pinus genome and occupy a physical space at least the size of the Arabidopsis thaliana genome. In contrast to previously described retroelements in Pinus, the Gymny family was amplified or introduced after the divergence of pine and spruce (Picea). If retrotransposon expansions are responsible for genome size differences within the Pinaceae, as they are in angiosperms, then they have yet to be identified. In contrast, molecular divergence of Gymny retrotransposons together with other families of retrotransposons can account for the large genome complexity of pines along with protein-coding genic DNA, as revealed by massively parallel DNA sequence analysis of Cot fractionated genomic DNA. CONCLUSIONS/SIGNIFICANCE: Most of the enormous genome complexity of pines can be explained by divergence of retrotransposons, however the elements responsible for genome size variation are yet to be identified. Genomic resources for Pinus including those reported here should assist in further defining whether and how the roles of retrotransposons differ in the evolution of angiosperm and gymnosperm genomes

    Measurements of inclusive and differential fiducial cross-sections of tt production with additional heavy-flavour jets in proton-proton collisions at √ s= 13 TeV with the ATLAS detector

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    This paper presents measurements of tt production in association with additional b-jets in pp collisions at the LHC at a centre-of-mass energy of 13 TeV. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. Fiducial cross-section measurements are performed in the dilepton and lepton-plus-jets tt decay channels. Results are presented at particle level in the form of inclusive cross-sections of tt final states with three and four b-jets as well as differential cross-sections as a function of global event properties and properties of b-jet pairs. The measured inclusive fiducial cross-sections generally exceed the ttbb predictions from various next-to-leading-order matrix element calculations matched to a parton shower but are compatible within the total uncertainties. The experimental uncertainties are smaller than the uncertainties in the predictions. Comparisons of state-of-the-art theoretical predictions with the differential measurements are shown and good agreement with data is found for most of them

    Search for Higgs bosons produced via vector-boson fusion and decaying into bottom quark pairs in √s =13 TeV pp collisions with the ATLAS detector

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    A search for the bb ¯ decay of the Standard Model Higgs boson produced through vector-boson fusion is presented. Three mutually exclusive channels are considered: two all-hadronic channels and a photon-associated channel. Results are reported from the analysis of up to 30.6 fb −1 of pp data at s √ =13 TeV collected with the ATLAS detector at the LHC. The measured signal strength relative to the Standard Model prediction from the combined analysis is 2.5 +1.4 −1.3 for inclusive Higgs boson production and 3.0 +1.7 −1.6 for vector-boson fusion production only

    Measurement of jet fragmentation in Pb+Pb and pp collisions at √s NN =5.02 TeV with the ATLAS detector

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    This paper presents a measurement of jet fragmentation functions in 0.49 nb −1 of Pb+Pb collisions and 25 pb −1 of pp collisions at √ sNN =5.02 TeV collected in 2015 with the ATLAS detector at the LHC. These measurements provide insight into the jet quenching process in the quark-gluon plasma created in the aftermath of ultra-relativistic collisions between two nuclei. The modifications to the jet fragmentation functions are quantified by dividing the measurements in Pb+Pb collisions by baseline measurements in pp collisions. This ratio is studied as a function of the transverse momentum of the jet, the jet rapidity, and the centrality of the collision. In both collision systems, the jet fragmentation functions are measured for jets with transverse momentum between 126 GeV and 398 GeV and with an absolute value of jet rapidity less than 2.1. An enhancement of particles carrying a small fraction of the jet momentum is observed, which increases with centrality and with increasing jet transverse momentum. Yields of particles carrying a very large fraction of the jet momentum are also observed to be enhanced. Between these two enhancements of the fragmentation functions a suppression of particles carrying an intermediate fraction of the jet momentum is observed in Pb+Pb collisions. A small dependence of the modifications on jet rapidity is observed
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