Toll-like receptor 2/MyD88 signaling mediates zymosan-induced joint hypernociception in mice: Participation of TNF-alpha, IL-1 beta and CXCL1/KC

Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. In the present study, it was addressed the participation of TLR2 and TLR4 and their adaptor molecule MyD88 in the genesis of joint hypernociception (a decrease in the nociceptive threshold) during zymosan-induced arthritis. Zymosan injected in the tibio-tarsal joint induced mechanical hypernociception in C57BL/6 wild type mice that was reduced in TLR2 and MyD88 null mice. On the other hand, zymosan-induced hypernociception was similar in C3H/HePas and C3H/Hej mice (TLR4 mutant mice). Zymosan-induced joint hypernociception was also reduced in TNFR1 null mice and in mice treated with IL-1 receptor antagonist or with an antagonist of CXCR1/2. Moreover, the joint production of TNF-alpha, IL-1 beta and CXCL1/KC by zymosan was dependent on TLR2/MyD88 signaling. Investigating the mechanisms by which TNF-alpha, IL-1 beta and CXCL1/KC mediate joint hypernociception, joint administration of these cytokines produced mechanical hypernociception, and they act in an interdependent manner. In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis. (C) 2011 Elsevier B.V. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq)Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Programa de Nucleos de Excelencia (PRONEX), Brazi

The ATP-sensitive potassium channel blocker glibenclamide prevents renal ischemia/reperfusion injury in rats

The ATP-sensitive potassium channel blocker glibenclamide prevents renal ischemia/reperfusion injury in rats.BackgroundRenal ischemia/reperfusion (I/R) is a complex neutrophil-mediated syndrome. Adenosine-triphosphate (ATP)-sensitive potassium (KATP) channels are involved in neutrophil migration in vivo. In the present study, we have investigated the effects of glibenclamide, a KATP channel blocker, in renal I/R injury in rats.MethodsThe left kidney of the rats was excised through a flank incision and ischemia was performed in the contralateral kidney by total interruption of renal artery flow for 45 minutes. Renal perfusion was reestablished, and the kidney and lungs were removed for analysis of vascular permeability, neutrophil accumulation, and content of cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-10] 4 and 24 hours later. Renal function was assessed by measuring creatinine, Na+, and K+ levels in the plasma and by determination of creatinine clearance. Drugs were administered subcutaneously after the onset of ischemia.ResultsReperfusion of the ischemic kidney induced local (kidney) and remote (lung) inflammatory injury and marked renal dysfunction. Glibenclamide (20 mg/kg) significantly inhibited the reperfusion-associated increase in vascular permeability, neutrophil accumulation, increase in TNF-α levels and nuclear factor-κB (NF-κB) translocation. These inhibitory effects were noticed in the kidney and lungs. Moreover, glibenclamide markedly ameliorated the renal dysfunction at 4 and 24 hours.ConclusionTreatment with glibenclamide is associated with inhibition of neutrophil recruitment and amelioration of renal dysfunction following renal I/R. Glibenclamide may have a therapeutic role in the treatment of renal I/R injury, such as after renal transplantation

Properties of 42 Solar-type Kepler Targets from the Asteroseismic Modeling Portal

Recently the number of main-sequence and subgiant stars exhibiting solar-like oscillations that are resolved into individual mode frequencies has increased dramatically. While only a few such data sets were available for detailed modeling just a decade ago, the Kepler mission has produced suitable observations for hundreds of new targets. This rapid expansion in observational capacity has been accompanied by a shift in analysis and modeling strategies to yield uniform sets of derived stellar properties more quickly and easily. We use previously published asteroseismic and spectroscopic data sets to provide a uniform analysis of 42 solar-type Kepler targets from the Asteroseismic Modeling Portal (AMP). We find that fitting the individual frequencies typically doubles the precision of the asteroseismic radius, mass and age compared to grid-based modeling of the global oscillation properties, and improves the precision of the radius and mass by about a factor of three over empirical scaling relations. We demonstrate the utility of the derived properties with several applications.Comment: 12 emulateapj pages, 9 figures, 1 online-only extended figure, 1 table, ApJS accepted (typo corrected in Eq.8

Siderophores as anchors in artificial metalloenzymes

Fundacao de Amparo a Pesquisa do Estado de Sao PauloConselho Nacional de Desenvolvimento Cientifico e TecnologicoCAPESInst Chem UNESP, Araraquara, SP, Brazil|Univ Fed Sao Paulo, EPM, Dept Pharmacol, Sao Paulo, SP, BrazilInst Chem USP, Sao Carlos, SP, BrazilUniv Fed Sao Paulo, EPM, Dept Pharmacol, Sao Paulo, SP, BrazilFAPESP: 2016/177115CNPqCAPESWeb of Scienc

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

The ALMA REBELS Survey: Dust Continuum Detections at z > 6.5

We report 18 dust continuum detections ($\geq 3.3\sigma$) at $\sim88{\rm \mu m}$ and $158{\rm \mu m}$ out of 49 ultraviolet(UV)-bright galaxies ($M_{\rm UV} 6.5$, observed by the Cycle-7 ALMA Large Program, REBELS and its pilot programs. This has more than tripled the number of dust continuum detections known at $z>6.5$. Out of these 18 detections, 12 are reported for the first time as part of REBELS. In addition, 15 of the dust continuum detected galaxies also show a [CII]$_{\rm 158{\rm \mu m}}$ emission line, providing us with accurate redshifts. We anticipate more line emission detections from six targets (including three continuum detected targets) where observations are still ongoing. The dust continuum detected sources in our sample tend to have a redder UV spectral slope than the ones without a dust continuum detection. We estimate that all of the sources have an infrared (IR) luminosity ($L_{\rm IR}$) in a range of $3-8 \times 10^{11} L_\odot$, except for one with $L_{\rm IR} = 1.5^{+0.8}_{-0.5} \times 10^{12}\,L_{\odot}$. Their fraction of obscured star formation is significant at $\gtrsim 50\%$. Some of the dust continuum detected galaxies show spatial offsets ($\sim 0.5-1.5''$) between the rest-UV and far-IR emission peaks. These separations appear to have an increasing trend against an indicator that suggests spatially decoupled phases of obscured and unobscured star formation. REBELS offers the best available statistical constraints on obscured star formation in UV-bright, massive galaxies at $z > 6.5$.Comment: 17 pages, 9 figures, submitted to MNRA

Prospects for asteroseismology

The observational basis for asteroseismology is being dramatically strengthened, through more than two years of data from the CoRoT satellite, the flood of data coming from the Kepler mission and, in the slightly longer term, from dedicated ground-based facilities. Our ability to utilize these data depends on further development of techniques for basic data analysis, as well as on an improved understanding of the relation between the observed frequencies and the underlying properties of the stars. Also, stellar modelling must be further developed, to match the increasing diagnostic potential of the data. Here we discuss some aspects of data interpretation and modelling, focussing on the important case of stars with solar-like oscillations.Comment: Proc. HELAS Workshop on 'Synergies between solar and stellar modelling', eds M. Marconi, D. Cardini & M. P. Di Mauro, Astrophys. Space Sci., in the press Revision: correcting abscissa labels on Figs 1 and

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