202 research outputs found

    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

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    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

    X-ray emission from the Sombrero galaxy: discrete sources

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    We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

    The Wnt Receptor Ryk Reduces Neuronal and Cell Survival Capacity by Repressing FOXO Activity During the Early Phases of Mutant Huntingtin Pathogenicity

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    The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD. Š 2014 Tourette et al

    A Precision Measurement of the Lambda_c Baryon Mass

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    The Λc+\Lambda_c^+ baryon mass is measured using Λc+→ΛKS0K+\Lambda_c^+\to\Lambda K^0_S K^+ and Λc+→Σ0KS0K+\Lambda_c^+\to\Sigma^0 K^0_S K^+ decays reconstructed in 232 fb−1^{-1} of data collected with the BaBar detector at the PEP-II asymmetric-energy e+e−e^+e^- storage ring. The Λc+\Lambda_c^+ mass is measured to be 2286.46±0.14MeV/c22286.46\pm0.14\mathrm{MeV}/c^2. The dominant systematic uncertainties arise from the amount of material in the tracking volume and from the magnetic field strength.Comment: 14 pages, 8 postscript figures, submitted to Phys. Rev.

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Meeting abstrac

    Measurement of the differential cross section for isolated prompt photon production in pp collisions at 7 TeV

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    A measurement of the differential cross section for the inclusive production of isolated prompt photons in proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The data sample corresponds to an integrated luminosity of 36 pb(-1) recorded by the CMS detector at the LHC. The measurement covers the pseudorapidity range vertical bar eta vertical bar < 2.5 and the transverse energy range 25 < E-T < 400 GeV, corresponding to the kinematic region 0.007 < x(T) < 0.114. Photon candidates are identified with two complementary methods, one based on photon conversions in the silicon tracker and the other on isolated energy deposits in the electromagnetic calorimeter. The measured cross section is presented as a function of E-T in four pseudorapidity regions. The next-to-leading-order perturbative QCD calculations are consistent with the measured cross section

    Search for supersymmetry in events with b jets and missing transverse momentum at the LHC

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    A search for supersymmetry is presented using a sample of events with b jets and missing transverse momentum. The search uses a data sample of proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 35 pb(-1), collected with the CMS detector. A total of 0.33(-0.33)(+0.43) (stat.) +/- 0.13 (syst.) events is predicted, using control samples in the data, to arise from standard model processes, and one event is observed in the data. Upper limits are set at the 95% confidence level on the cross sections of benchmark supersymmetric models

    Indications of suppression of excited Υ states in Pb-Pb collisions at √sNN = 2.76TeV

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    This is the pre-print version of the Published Article which can be accessed from the link below.A comparison of the relative yields of Υ resonances in the μ+μ- decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the double ratio of the Υ(2S) and Υ(3S) excited states to the Υ(1S) ground state in Pb-Pb and pp collisions, [Υ(2S+3S)/Υ(1S)]Pb-Pb/[Υ(2S+3S)/Υ(1S)]pp, is found to be 0.31-0.15+0.19(stat)±0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%

    Measurement of the t-channel single top quark production cross section in pp collisions at √s = 7TeV

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    This is the pre-print version of the Published Article which can be accessed from the link below.Electroweak production of the top quark is measured for the first time in pp collisions at √s=7  TeV, using a data set collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36  pb-1. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from the data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top-quark production. The combined measurement of the cross section is 83.6±29.8(stat+syst)±3.3(lumi)  pb, consistent with the standard model expectation
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