340 research outputs found

    Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

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    BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

    Bark anatomy, chemical composition and ethanol-water extract composition of Anadenanthera peregrina and Anadenanthera colubrina

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    The bark of Anadenanthera peregrina (L.) Speg and Anadenanthera colubrina (Vell.) Brenan were characterized in relation to anatomical and chemical features. The barks were similar and included a thin conducting phloem, a largely dilated and sclerified non-conducting phloem, and a rhyridome with periderms with thin phellem interspersed by cortical tissues. Only small differences between species were observed that cannot be used alone for taxonomic purposes. The summative chemical composition of A. peregrina and A. colubrina was respectively: 8.2% and 7.7% ash; 28.8% and 29.3% extractives; 2.4% and 2.6% suberin; and 18.9% lignin. The monosaccharide composition showed the predominance of glucose (on average 82% of total neutral sugars) and of xylose (9%). The ethanol-water extracts of A. peregrina and A. colubrina barks included a high content of phenolics, respectively: total phenolics 583 and 682 mg GAE/g extract; 148 and 445 mg CE/g extract; tannins 587 and 98 mg CE/g extract. The antioxidant activity was 238 and 269 mg Trolox/g extract. The barks of the Anadenanthera species are a potential source of polar extractives that will represent an important valorization and therefore contribute to improve the overall economic potential and sustainability of A. peregrina and A. colubrinainfo:eu-repo/semantics/publishedVersio

    DNA resection in eukaryotes: deciding how to fix the break

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    DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

    Influence of ovarian hormones deprivation on gene expression in the lower urinary tract of rats

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    OBJECTIVE: Identify the influence of ovarian hormone deprivation in expression genes on the lower urinary tract of rats. MATERIALS AND METHODS: This study deals with gene screening on lower urinary tract of rats. Fifty isogenic rats divided in two groups of twenty-five animals have their lower urinary tract surgically removed: group I, ovariectomized rats 30 days prior to surgery; group II, non-ovariectomized rats. Total RNA was isolated from bladder and urethra, and differential expression of genes was analyzed quantitative, qualitative and comparatively by array technology and RT-PCR. RESULTS: A total of 76 candidate genes were identified as differentially expressed between the groups, 26 being lower expressed in group II, and 50 in group I. Among them, differential expression validation was confirmed by RT-PCR for three lower expressed genes in group I: Vascular Endothelial Growth Factor (VEGF), Beta-2 Microglobulin (B2M) and Cytochrome c Oxidase subunit I (COX I). CONCLUSION: Ovarian hormone deprivation influences the expression genes on lower urinary tract. We demonstrated that a 30-day period of castration down regulate the expression of VEGF, B2M and COX I in adult rats which are involved in activities of angiogenesis, immune responses and cellular metabolism respectively.Federal University of São Paulo Department of GynecologyUNIFESP, Department of GynecologySciEL

    Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

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    We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

    Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

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    We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

    Measurement of the W+WW^+W^- Production Cross Section and Search for Anomalous WWγWW\gamma and WWZWWZ Couplings in ppˉp \bar p Collisions at s=1.96\sqrt{s} = 1.96 TeV

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    This Letter describes the current most precise measurement of the WW boson pair production cross section and most sensitive test of anomalous WWγWW\gamma and WWZWWZ couplings in ppˉp \bar p collisions at a center-of-mass energy of 1.96 TeV. The WWWW candidates are reconstructed from decays containing two charged leptons and two neutrinos, where the charged leptons are either electrons or muons. Using data collected by the CDF II detector from 3.6 fb1^{-1} of integrated luminosity, a total of 654 candidate events are observed with an expected background contribution of 320±47320 \pm 47 events. The measured total cross section is σ(ppˉW+W+X)=12.1±0.9(stat)1.4+1.6(syst)\sigma (p \bar p \to W^+ W^- + X) = 12.1 \pm 0.9 \textrm{(stat)} ^{+1.6}_{-1.4} \textrm{(syst)} pb, which is in good agreement with the standard model prediction. The same data sample is used to place constraints on anomalous WWγWW\gamma and WWZWWZ couplings.Comment: submitted to Phys. Rev. Let

    Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

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    We present a search for a new heavy charged vector boson WW^\prime decaying to an electron-neutrino pair in ppˉp\bar{p} collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on σB(Weν)\sigma\cdot{\cal B}(W^\prime\to e\nu). Assuming standard model couplings to fermions and the neutrino from the WW^\prime boson decay to be light, we exclude a WW^\prime boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

    Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

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    We reconstruct the rare decays B+K+μ+μB^+ \to K^+\mu^+\mu^-, B0K(892)0μ+μB^0 \to K^{*}(892)^0\mu^+\mu^-, and Bs0ϕ(1020)μ+μB^0_s \to \phi(1020)\mu^+\mu^- in a data sample corresponding to 4.4fb14.4 {\rm fb^{-1}} collected in ppˉp\bar{p} collisions at s=1.96TeV\sqrt{s}=1.96 {\rm TeV} by the CDF II detector at the Fermilab Tevatron Collider. Using 121±16121 \pm 16 B+K+μ+μB^+ \to K^+\mu^+\mu^- and 101±12101 \pm 12 B0K0μ+μB^0 \to K^{*0}\mu^+\mu^- decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the B+B^+ and B0B^0 decay modes, and the K0K^{*0} longitudinal polarization in the B0B^0 decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the Bs0ϕμ+μdecayandmeasureitsbranchingratioB^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio {\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}using using 27 \pm 6signalevents.Thisiscurrentlythemostrare signal events. This is currently the most rare B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
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