Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone.Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin.Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB4 and nitrites while bone marrow cells increased the release of TNF-α and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-α, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF- α by cultured BAL cells and bone marrow cells.Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed. © 2010 de Oliveira et al; licensee BioMed Central Ltd.

Relativistic three-body model for final state interaction in D+ → K-π+π+ decay

A challenge in mesonic three-body decays of heavy mesons is to quantify the contribution of re-scattering between the final mesons. D decays have the unique feature that make them a key to light meson spectroscopy, in particular to access the Kn S-wave phase-shifts. We built a relativis-tic three-body model for the final state interaction in D+ → K -π+π+ decay based on the ladder approximation of the Bethe-Salpeter equation projected on the light-front. The decay amplitude is separated in a smooth term, given by the direct partonic decay amplitude, and a three-body fully interacting contribution, that is factorized in the standard two-meson resonant amplitude times a reduced complex amplitude that carries the effect of the three-body rescattering mechanism. The off-shell reduced amplitude is a solution of an inhomogeneous Faddeev type three-dimensional integral equation, that includes only isospin 1/2 K -π+ interaction in the S-wave channel. The elastic K-π+ scattering amplitude is parameterized according to the LASS data[1]. The integral equation is solved numerically and preliminary results are presented and compared to the experimental data from the E791 Collaboration[2, 3] and FOCUS Collaboration[4, 5].

Study of the decay Bs0→J/ψf2′(1525) in μ +μ -K +K - final states

We investigate the decay Bs0→J/ψK +K - for invariant masses of the K +K - pair in the range 1.35data sample corresponds to an integrated luminosity of 10.4fb -1 of pp̄ collisions at √s=1.96TeV accumulated with the D0 detector at the Fermilab Tevatron collider. From the study of the invariant mass and spin of the K +K - system, we find evidence for the two-body decay Bs0→J/ψf2′(1525) and measure the relative branching fraction of the decays Bs0→J/ψf2′(1525) and Bs0→J/ψ to be R f2′/=0.19±0.05(stat)±0.04(syst). © 2012 American Physical Society.

Measurement of the top-quark mass in t̄t events with lepton+jets final states in pp collisions at √s =7 TeV

The mass of the top quark is measured using a sample of t̄t candidate events with one electron or muon and at least four jets in the final state, collected by CMS in pp collisions at √s =7 TeV at the LHC. A total of 5174 candidate events is selected from data corresponding to an integrated luminosity of 5.0 fb-1. For each event the mass is reconstructed from a kinematic fit of the decay products to a t̄t hypothesis. The top-quark mass is determined simultaneously with the jet energy scale (JES), constrained by the known mass of the W boson in q̄q decays, to be 173.49 ± 0.43 (stat. + JES) ±0.98 (syst.) GeV. © 2012 CERN for the benefit of the CMS collaboration.

Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: Radiochemical and real-time video-microscopy studies

Understanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA2 homologue from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 μM) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [3H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. © 2012 Elsevier Ltd.

Search for supersymmetry in final states with missing transverse energy and 0, 1, 2, or ≥3 b-quark jets in 7 TeV pp collisions using the variable α T

A search for supersymmetry in final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of s=7 TeV. The data sample corresponds to an integrated luminosity of 4.98 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, α T, is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. The search is performed in a signal region that is binned in the scalar sum of the transverse energy of jets and the number of jets identified as originating from a bottom quark. No excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of the constrained minimal supersymmetric extension of the standard model, and also in simplified models, with a special emphasis on compressed spectra and third-generation scenarios.[Figure not available: see fulltext.] © 2013 CERN for the benefit of the CMS Collaboration.

Search for supersymmetry in final states with a single lepton, b-quark jets, and missing transverse energy in proton-proton collisions at √s=7 TeV

A search motivated by supersymmetric models with light top squarks is presented using proton-proton collision data recorded with the CMS detector at a center-of-mass energy of √s=7 TeV during 2011, corresponding to an integrated luminosity of 4.98 fb-1. The analysis is based on final states with a single lepton, b-quark jets, and missing transverse energy. Standard model yields are predicted from data using two different approaches. The observed event numbers are found to be compatible with these predictions. Results are interpreted in the context of the constrained minimal supersymmetric standard model and of a simplified model with four top quarks in the final state. © 2013 CERN.

Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Background: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion. © 2013 Guido et al.; licensee BioMed Central Ltd.

Search for Z′ resonances decaying to tt̄ in dilepton+jets final states in pp collisions at √s=7 TeV

A search for resonances decaying to top quark-antiquark pairs is performed using a dilepton+jets data sample recorded by the CMS experiment at the LHC in pp collisions at √s=7 TeV corresponding to an integrated luminosity of 5.0 fb-1. No significant deviations from the standard model background are observed. Upper limits are presented for the production cross section times branching fraction of top quark-antiquark resonances for masses from 750 to 3000 GeV. In particular, the existence of a leptophobic topcolor particle Z′ is excluded at the 95% confidence level for resonance masses MZ ′<1.3 TeV for ΓZ′=0.012MZ ′, and M<1.9 TeV for ΓZ′=0.10MZ ′. © 2013 CERN.

Search for pair-produced dijet resonances in four-jet final states in pp collisions at √s=7 TeV

A search for the pair production of a heavy, narrow resonance decaying into two jets has been performed using events collected in √s=7 TeV pp collisions with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 5.0 fb-1. Events are selected with at least four jets and two dijet combinations with similar dijet mass. No resonances are found in the dijet mass spectrum. The upper limit at 95% confidence level on the product of the resonance pair production cross section, the branching fractions into dijets, and the acceptance varies from 0.22 to 0.005 pb, for resonance masses between 250 and 1200 GeV. Pair-produced colorons decaying into qq̄ are excluded for coloron masses between 250 and 740 GeV. © 2013 CERN. citation, and DOI.

Search for new physics in final states with a lepton and missing transverse energy in pp collisions at the LHC

This Letter describes the search for an enhanced production rate of events with a charged lepton and a neutrino in high-energy pp collisions at the LHC. The analysis uses data collected with the CMS detector, with an integrated luminosity of 5.0 fb-1 at √s=7 TeV, and a further 3.7 fb -1 at √s=8 TeV. No evidence is found for an excess. The results are interpreted in terms of limits on a heavy charged gauge boson (W ′) in the sequential standard model, a split universal extra dimension model, and contact interactions in the helicity-nonconserving model. For the last, values of the binding energy below 10.5 (8.8) TeV in the electron (muon) channel are excluded at a 95% confidence level. Interpreting the ℓν final state in terms of a heavy W′ with standard model couplings, masses below 2.90 TeV are excluded. © 2013 CERN.

Measurement of the t̄t production cross section in the all-jet final state in pp collisions at √s=7 TeV

A measurement is presented of the t̄t production cross section σt̄t in proton-proton collisions at a centre-of-mass energy of 7 TeV, in the all-jet final state that contains at least six jets, two of which are tagged as originating from b quarks. The data correspond to an integrated luminosity of 3.54 fb-1, collected with the CMS detector at the LHC. The cross section is determined through an unbinned maximum likelihood fit of background and t̄t signal to the reconstructed mass spectrum of t̄t candidates in the data, in which events are subjected to a kinematic fit assuming a t̄t → W+bW-̄b → 6 jets hypothesis. The measurement yields σt̄t = 139±10(stat.)±26(syst.)±3(lum.)pb, a result consistent with those obtained in other t̄t decay channels, as well as with predictions of the standard model. © 2013 CERN for the benefit of the CMS collaboration.

Rastreamento de polimorfsmos no gene HIOMT e associações com os fenótipos circadianos

HIOMT is a gene that encodes hydroxyindole-O-methyltransfe-rase, the final enzyme in the melatonin synthesis pathway. As the timing of melatonin synthesis is different for morning and evening people, it is possible that polymorphisms in genes coding for the enzymes which participate in melatonin synthesis can influence this hormone synthesis and release patterns that may result in different circadian outputs. The aim of this study was to search for polymorphisms in the HIOMT gene and to verify possible associations between genetic variations in this gene and circadian phenotypes in a Brazilian population sample. Among the 44 extreme morning and the 48 extreme evening people, ten polymorphisms were found, being two of them not described so far. Haploview analyses showed linkage disequilibrium between pairs of polymorphisms in the promoter B region. Also, the haplotype AG (rs4446909, rs5989681) is associated with evening preference. The analysis of these data indicates that polymorphisms in the HIOMT gene exhibit a possible trend to influence circadian phenotypes in this Brazilian population sample, possibly affecting the rate and/or level of melatonin synthesis.

Search for supersymmetry in hadronic final states with missing transverse energy using the variables αT and b-quark multiplicity in pp collisions at {Mathematical expression}

An inclusive search for supersymmetric processes that produce final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of 8 TeV. The data sample corresponds to an integrated luminosity of 11.7 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, αT, is used to discriminate between events with genuine and misreconstructed missing transverse energy. The search is based on an examination of the number of reconstructed jets per event, the scalar sum of transverse energies of these jets, and the number of these jets identified as originating from bottom quarks. No significant excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of simplified models, with a special emphasis on both compressed-spectrum scenarios and direct or gluino-induced production of third-generation squarks. For the case of gluino-mediated squark production, gluino masses up to 950-1125 GeV are excluded depending on the assumed model. For the direct pair-production of squarks, masses up to 450 GeV are excluded for a single light first- or second-generation squark, increasing to 600 GeV for bottom squarks. © 2013 CERN for the benefit of the CMS collaboration.

Search for gluino mediated bottom- and top-squark production in multijet final states in pp collisions at 8 TeV

A search for supersymmetry is presented based on events with large missing transverse energy, no isolated electron or muon, and at least three jets with one or more identified as a bottom-quark jet. A simultaneous examination is performed of the numbers of events in exclusive bins of the scalar sum of jet transverse momentum values, missing transverse energy, and bottom-quark jet multiplicity. The sample, corresponding to an integrated luminosity of 19.4fb-1, consists of proton-proton collision data recorded at a center-of-mass energy of 8TeV with the CMS detector at the LHC in 2012. The observed numbers of events are found to be consistent with the standard model expectation, which is evaluated with control samples in data. The results are interpreted in the context of two simplified supersymmetric scenarios in which gluino pair production is followed by the decay of each gluino to an undetected lightest supersymmetric particle and either a bottom or top quark-antiquark pair, characteristic of gluino mediated bottom- or top-squark production. Using the production cross section calculated to next-to-leading-order plus next-to-leading-logarithm accuracy, and in the limit of a massless lightest supersymmetric particle, we exclude gluinos with masses below 1170GeV and 1020GeV for the two scenarios, respectively. © 2013 CERN.