59 research outputs found

    Regulation of ␣4␤2 Nicotinic Receptor Desensitization by Calcium and Protein Kinase C

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    ABSTRACT Neuronal nicotinic acetylcholine receptor (nAChR) desensitization is hypothesized to be a trigger for long-term changes in receptor number and function observed after chronic administration of nicotine at levels similar to those found in persons who use tobacco. Factors that regulate desensitization could potentially influence the outcome of long-lasting exposure to nicotine. The roles of Ca 2ϩ and protein kinase C (PKC) on desensitization of ␣4␤2 nAChRs expressed in Xenopus laevis oocytes were investigated. Nicotine-induced (300 nM; 30 min) desensitization of ␣4␤2 receptors in the presence of Ca 2ϩ developed in a biphasic manner with fast and slow exponential time constants of f ϭ 1.4 min (65% relative amplitude) and s ϭ 17 min, respectively. Recovery from desensitization was reasonably well described by a single exponential with rec ϭ 43 min. Recovery was largely eliminated after replacement of external Ca 2ϩ with Ba 2ϩ and slowed by calphostin C ( rec ϭ 48 min), an inhibitor of PKC. Conversely, the rate of recovery was enhanced by phorbol-12-myristate-13-acetate ( rec ϭ 14 min), a PKC activator, or by cyclosporin A (with rec ϭ 8 min), a phosphatase inhibitor. ␣4␤2 receptors containing a mutant ␣4 subunit that lacks a consensus PKC phosphorylation site exhibited little recovery from desensitization. Based on a twodesensitized-state cyclical model, it is proposed that after prolonged nicotine treatment, ␣4␤2 nAChRs accumulate in a "deep" desensitized state, from which recovery is very slow. We suggest that PKC-dependent phosphorylation of ␣4 subunits changes the rates governing the transitions from "deep" to "shallow" desensitized conformations and effectively increases the overall rate of recovery from desensitization. Longlasting dephosphorylation may underlie the "permanent" inactivation of ␣4␤2 receptors observed after chronic nicotine treatment

    Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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    Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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    Cross section measurement of t-channel single top quark production in pp collisions at root s=13 TeV

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    Measurement of the top quark mass using single top quark events in proton-proton collisions at root s=8 TeV

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    Search for single production of vector-like quarks decaying into a b quark and a W boson in proton-proton collisions at root s=13 TeV

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    Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at root s=13 TeV

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    Search for supersymmetry in proton-proton collisions at 13 TeV using identified top quarks

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    A search for supersymmetry is presented based on proton-proton collision events containing identified hadronically decaying top quarks, no leptons, and an imbalance p(T)(miss) in transverse momentum. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). Search regions are defined in terms of the multiplicity of bottom quark jet and top quark candidates, the p(T)(miss) , the scalar sum of jet transverse momenta, and themT2 mass variable. No statistically significant excess of events is observed relative to the expectation from the standard model. Lower limits on the masses of supersymmetric particles are determined at 95% confidence level in the context of simplified models with top quark production. For a model with direct top squark pair production followed by the decay of each top squark to a top quark and a neutralino, top squark masses up to 1020 GeVand neutralino masses up to 430 GeVare excluded. For amodel with pair production of gluinos followed by the decay of each gluino to a top quark-antiquark pair and a neutralino, gluino masses up to 2040 GeVand neutralino masses up to 1150 GeVare excluded. These limits extend previous results.Peer reviewe

    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

    Pseudorapidity distributions of charged hadrons in proton-lead collisions at root s(NN)=5:02 and 8.16 TeV

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    The pseudorapidity distributions of charged hadrons in proton-lead collisions at nucleon-nucleon center-of-mass energies root s(NN) = 5.02 and 8.16 TeV are presented. The measurements are based on data samples collected by the CMS experiment at the LHC. The number of primary charged hadrons produced in non-single-diffractive proton-lead collisions is determined in the pseudorapidity range vertical bar eta(lab)vertical bar vertical bar(vertical bar eta cm vertical bar) <0.5 are 17.1 +/- 0.01 (stat) +/- 0.59 (syst) and 20.10 +/- 0.01 (stat) +/- 0.5(syst) at root s(NN) = 5.02 and 8.16 TeV, respectively. The particle densities per participant nucleon are compared to similar measurements in proton-proton, proton-nucleus, and nucleus-nucleus collisions.Peer reviewe
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