1,290 research outputs found
The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytes
BNIP3 is a recently described pro-apoptotic member of the Bcl-2 family and in BNIP3 cDNA-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Delta psi m). However, its expression or function in physiologic cell types is not known. Our results using the T-cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl-2 family pro-apoptotic molecules, BNIP3 is transcriptionally highly up-regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation-induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3-induced cell death. AICD of CTL was caspase-independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3-induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Delta psi m. Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T-cell homeostasis by regulating effector CTL numbers
Search for Z′ bosons decaying to pairs of heavy Majorana neutrinos in proton-proton collisions at s = 13 TeV
Abstract A search for the production of pairs of heavy Majorana neutrinos (N ℓ ) from the decays of Z′ bosons is performed using the CMS detector at the LHC. The data were collected in proton-proton collisions at a center-of-mass energy of s = 13 TeV, with an integrated luminosity of 138 fb −1. The signature for the search is an excess in the invariant mass distribution of the final-state objects, two same-flavor leptons (e or μ) and at least two jets. No significant excess of events beyond the expected background is observed. Upper limits at 95% confidence level are set on the product of the Z′ production cross section and its branching fraction to a pair of N ℓ , as functions of N ℓ and Z′ boson masses ( m N ℓ and m Z ′ , respectively) for m Z ′ from 0.4 to 4.6 TeV and m N ℓ from 0.1 TeV to m Z ′ /2. In the theoretical framework of a left-right symmetric model, exclusion bounds in the m N ℓ - m Z ′ plane are presented in both the electron and muon channels. The observed upper limit on m Z ′ reaches up to 4.42 TeV. These are the most restrictive limits to date on the mass of N ℓ as a function of the Z′ boson mass
IL-7 plays a critical role for the homeostasis of allergen-specific memory CD4 T cells in the lung and airways
Memory T cells respond rapidly to repeated antigen exposure and can maintain their population for extended periods through self-renewal. These characteristics of memory T cells have mainly been studied during viral infections, whereas their existence and functions in allergic diseases have been studied incompletely. Since allergic patients can suffer repeated relapses caused by intermittent allergen exposure, we hypothesized that allergen- specific memory Th2 cells are present and the factors necessary for the maintenance of these cells are provided by the lung and airways. Using a murine model of airway inflammation, we found that allergen-specific CD4 T cells survived longer than 70 days in the lung and airways in an IL-7 dependent fashion. These T cells showing homeostatic proliferation were largely found in the mediastinal lymph node (mLN), rather than the airways; however, cells residing in the lung and airways developed recall responses successfully. We also found that CD4 T cells exhibited differential phenotypes in the mLN and in the lung. Altogether, we believe that allergen-specific memory T cells reside and function in the lung and airways, while their numbers are replenished through homeostatic turnover in the mLNs. Furthermore, we determined that IL-7 signaling is important for the homeostasis of these cells.
PDZ-mediated interactions retain the epithelial GABA transporter on the basolateral surface of polarized epithelial cells
The PDZ target motifs located in the C-terminal end of many receptors and ion channels mediate protein–protein interactions by binding to specific
PDZ-containing proteins. These interactions are involved in the localization of surface proteins on specialized membrane domains of neuronal and epithelial cells. However, the molecular mechanism responsible for this PDZ protein-dependent polarized localization is still unclear. This study first demonstrated
that the epithelial g-aminobutyric acid (GABA)transporter (BGT-1) contains a PDZ target motif that mediates the interaction with the PDZ protein LIN-7 in Madin–Darby canine kidney (MDCK) cells, and then investigated the role of this interaction in
the basolateral localization of the transporter. It was found that although the transporters from which the PDZ target motif was deleted were still targeted to
the basolateral surface, they were not retained but internalized in an endosomal recycling compartment.Furthermore, an interfering BGT peptide determined
the intracellular relocation of the native transporter. These data indicate that interactions with PDZ proteins determine the polarized surface localization of target proteins by means of retention and not
targeting mechanisms. PDZ proteins may, therefore, act as a sort of membrane protein sorting machinery which, by recognizing retention signals (the PDZtarget sequences), prevents protein internalization
Search for high-mass exclusive γγ → WW and γγ → ZZ production in proton-proton collisions at s = 13 TeV
Abstract A search is performed for exclusive high-mass γγ → WW and γγ → ZZ production in proton-proton collisions using intact forward protons reconstructed in near-beam detectors, with both weak bosons decaying into boosted and merged jets. The analysis is based on a sample of proton-proton collisions collected by the CMS and TOTEM experiments at s = 13 TeV, corresponding to an integrated luminosity of 100 fb −1. No excess above the standard model background prediction is observed, and upper limits are set on the pp → pWWp and pp → pZZp cross sections in a fiducial region defined by the diboson invariant mass m(VV) > 1 TeV (with V = W, Z) and proton fractional momentum loss 0.04 < ξ < 0.20. The results are interpreted as new limits on dimension-6 and dimension-8 anomalous quartic gauge couplings
Measurement of the B s 0 → J / ψK S 0 effective lifetime from proton-proton collisions at s = 13 TeV
Abstract The effective lifetime of the B s 0 meson in the decay B s 0 → J / ψK S 0 is measured using data collected during 2016–2018 with the CMS detector in s = 13 TeV proton-proton collisions at the LHC, corresponding to an integrated luminosity of 140 fb−1. The effective lifetime is determined by performing a two-dimensional unbinned maximum likelihood fit to the B s 0 meson invariant mass and proper decay time distributions. The resulting value of 1.59 ± 0.07(stat) ± 0.03(syst) ps is the most precise measurement to date and is in good agreement with the expected value
Loss of CD127 (Interleukin-7 receptor) expression defines an expansion of “effector memory” CD8+Tcells in HIV-infected patients
Author Correction: A portrait of the Higgs boson by the CMS experiment ten years after the discovery
In the version of this article initially published, CMS Collaboration author names, affiliations and acknowledgements were omitted and have now been included in the HTML and PDF versions of the articl
Search for a high-mass dimuon resonance produced in association with b quark jets at s = 13 TeV
A search for high-mass dimuon resonance production in association with one or more b quark jets is presented. The study uses proton-proton collision data collected with the CMS detector at the LHC corresponding to an integrated luminosity of 138 fb−1 at a center-of-mass energy of 13 TeV. Model-independent limits are derived on the number of signal events with exactly one or more than one b quark jet. Results are also interpreted in a lepton-flavor-universal model with Z′ boson couplings to a bb quark pair (gb), an sb quark pair (gbδbs), and any same-flavor charged lepton (gℓ) or neutrino pair (gν), with |gν| = |gℓ|. For a Z′ boson with a mass
m
Z
′
= 350 GeV (2 TeV) and |δbs| < 0.25, the majority of the parameter space with 0.0057 < |gℓ| < 0.35 (0.25 < |gℓ| < 0.43) and 0.0079 < |gb| < 0.46 (0.34 < |gb| < 0.57) is excluded at 95% confidence level. Finally, constraints are set on a Z′ model with parameters consistent with low-energy b → sℓℓ measurements. In this scenario, most of the allowed parameter space is excluded for a Z′ boson with 350 <
m
Z
′
< 500 GeV, while the constraints are less stringent for higher
m
Z
′
hypotheses. This is the first dedicated search at the LHC for a high-mass dimuon resonance produced in association with multiple b quark jets, and the constraints obtained on models with this signature are the most stringent to date
Search for long-lived particles using out-of-time trackless jets in proton-proton collisions at s = 13 TeV
Abstract A search for long-lived particles decaying in the outer regions of the CMS silicon tracker or in the calorimeters is presented. The search is based on a data sample of proton-proton collisions at s = 13 TeV recorded with the CMS detector at the LHC in 2016–2018, corresponding to an integrated luminosity of 138 fb −1. A novel technique, using nearly trackless and out-of-time jet information combined in a deep neural network discriminator, is employed to identify decays of long-lived particles. The results are interpreted in a simplified model of chargino-neutralino production, where the neutralino is the next-to-lightest supersymmetric particle, is long-lived, and decays to a gravitino and either a Higgs or Z boson. This search is most sensitive to neutralino proper decay lengths of approximately 0.5 m, for which masses up to 1.18 TeV are excluded at 95% confidence level. The current search is the best result to date in the mass range from the kinematic limit imposed by the Higgs boson mass up to 1.8 TeV
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