IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23

Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

10.1186/1756-9966-29-134Journal of Experimental and Clinical Cancer Research29113

Epidermal Langerhans Cells-A Target for HTLV-III/LAV Infection

Langerhans cells (LC) are bone marrow-derived, la+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS

Demographic and Clinical Variation in Veterans Health Administration Provision of Assistive Technology Devices to Veterans Poststroke

Objectives: To examine variation in provision of assistive technology (AT) devices and the extent to which such variation may be explained by patient characteristics or Veterans Health Administration (VHA) administrative region. Design: Retrospective population-based study. Setting: VHA. Participants: Veterans poststroke in fiscal years 2001 and 2002 (N=12,046). Interventions: Not applicable. Main Outcome Measure: Provision of 8 categories of AT devices. Results: There was considerable regional variation in provision of AT. For example, differences across administrative regions in the VHA ranged from 5.1 to 28.1 standard manual wheelchairs per 100 veterans poststroke. Using logistic regression, with only demographic variables as predictors of standard manual wheelchair provision, the c statistic was .62, and the pseudo R2 was 2.5%. Adding disease severity increased the c statistic to .67 and the pseudo R2 to 6.2%, and adding Veteran Integrated Network System further increased the c statistic to .72 and pseudo R2 to 9.8%. Conclusions: Our research showed significant variation in the provision of AT devices to veterans poststroke, and it showed that patient characteristics accounted for only 6.2% of the variation. VHA administrative region and disability severity accounted for equivalent amounts of the variation

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of B+π− and B0π+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb−1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B1(5721)0,+ and B2(5747)0,+ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B+π− and B0π+ combinations. The structures are consistent with the presence of four excited B mesons, labelled BJ (5840)0,+ and BJ (5960)0,+, whose masses and widths are obtained under different hypotheses for their quantum numbers

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson