267 research outputs found

    Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

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    Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS

    Search for R-parity violating supersymmetry with displaced vertices in proton-proton collisions at root s=8 TeV

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    Search for dijet resonances in proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

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    Correction: DOI:10.1016/j.physletb.2017.09.029Peer reviewe

    Observation of Top Quark Production in Proton-Nucleus Collisions

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    Observation of top quark pairs produced in association with a vector boson in pp collisions at s=8 √s=8TeV

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    Measurements of the cross sections for top quark pairs produced in association with a W or Z boson are presented, using 8 TeV pp collision data corresponding to an integrated luminosity of 19.5 fb −1 , collected by the CMS experiment at the LHC. Final states are selected in which the associated W boson decays to a charged lepton and a neutrino or the Z boson decays to two charged leptons. Signal events are identified by matching reconstructed objects in the detector to specific final state particles from t t ¯ W tt¯W or t t ¯ Z tt¯Z decays. The t t ¯ W tt¯W cross section is measured to be 382 − 102 + 117 fb with a significance of 4.8 standard deviations from the background-only hypothesis. The t t ¯ Z tt¯Z cross section is measured to be 242 − 55 + 65 fb with a significance of 6.4 standard deviations from the background-only hypothesis. These measurements are used to set bounds on five anomalous dimension-six operators that would affect the t t ¯ W tt¯W and t t ¯ Z tt¯Z cross sections

    Search for supersymmetry in events with a photon, a lepton, and missing transverse momentum in pp collisions at root s=8 TeV

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    Measurements of (tt)over-barH Production and the CP Structure of the Yukawa Interaction between the Higgs Boson and Top Quark in the Diphoton Decay Channel

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    The first observation of the (tt) over barH process in a single Higgs boson decay channel with the full reconstruction of the final state (H -> gamma gamma) is presented, with a significance of 6.6 standard deviations (sigma). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2 sigma. The measurements are based on a sample of protonproton collisions at a center-of-mass energy root s = 13 TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross section times branching fraction of the (tt) over barH process is measured to be sigma B-(tt) over barH(gamma gamma) = 1.56(-0.32)(+0.34) th, which is compatible with the standard model prediction of 1.13(-0.11)(+0.08) fb. The fractional contribution of the CP-odd component is measured to be f(CP)(Hu) = 0.00 +/- 0.33.Peer reviewe

    Limits on the Higgs boson lifetime and width from its decay to four charged leptons

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    Nuclear modification of Y states in pPb collisions at √SNN_{NN} = 5.02 TeV

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    Production cross sections of Υ(1S), Υ(2S), and Υ(3S) states decaying into μ+μ− in proton-lead (pPb) collisions are reported using data collected by the CMS experiment at √sNN = 5.02 TeV. A comparison is made with corresponding cross sections obtained with pp data measured at the same collision energy and scaled by the Pb nucleus mass number. The nuclear modification factor for Υ(1S) is found to be RpPb(Υ(1S)) = 0.806±0.024 (stat)±0.059 (syst). Similar results for the excited states indicate a sequential suppression pattern, such that RpPb(Υ(1S)) > RpPb(Υ(2S)) > RpPb(Υ(3S)). The suppression of all states is much less pronounced in pPb than in PbPb collisions, and independent of transverse momentum pΥT and center-of-mass rapidity yΥCM of the individual Υ state in the studied range p ΥT < 30 GeV/c and |yΥCM| <1.93. Models that incorporate final-state effects of bottomonia in pPb collisions are in better agreement with the data than those which only assume initial-state modifications

    Angular analysis of the decay B-0 -> K*(0)mu(+)mu(-) from pp collisions at root s=8 TeV

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