631 research outputs found
Syk activation in circulating and tissue innate immune cells in antineutrophil cytoplasmic antibody-associated vasculitis
OBJECTIVE: Syk is a cytoplasmic protein tyrosine kinase that plays a role in signaling via B cell and Fc receptors (FcR). FcR engagement and signaling via Syk is thought to be important in antineutrophil cytoplasm antibody (ANCA) IgG-mediated neutrophil activation. This study was undertaken to investigate the role of Syk in ANCA-induced myeloid cell activation and vasculitis pathogenesis. METHODS: Phosphorylation of Syk in myeloid cells from healthy controls and ANCA-associated vasculitis (AAV) patients was analyzed using flow cytometry. The effect of Syk inhibition on myeloperoxidase (MPO)-ANCA IgG activation of cells was investigated using functional assays (interleukin-8 and reactive oxygen species production) and targeted gene analysis with NanoString. Total and phosphorylated Syk at sites of tissue inflammation in patients with AAV was assessed using immunohistochemistry and RNAscope in situ hybridization. RESULTS: We identified increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes from patients with active AAV compared to patients with disease in remission or healthy controls. Syk was phosphorylated in vitro following MPO-ANCA IgG stimulation, and Syk inhibition was able to prevent ANCA-mediated cellular responses. Using targeted gene expression analysis, we identified up-regulation of FcR- and Syk-dependent signaling pathways following MPO-ANCA IgG stimulation. Finally, we showed that Syk is expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV. CONCLUSION: These findings indicate that Syk plays a critical role in MPO-ANCA IgG-induced myeloid cell responses and that Syk is activated in circulating immune cells and tissue immune cells in AAV; therefore, Syk inhibition may be a potential therapeutic option
Assessing the Health of Richibucto Estuary with the Latent Health Factor Index
The ability to quantitatively assess the health of an ecosystem is often of
great interest to those tasked with monitoring and conserving ecosystems. For
decades, research in this area has relied upon multimetric indices of various
forms. Although indices may be numbers, many are constructed based on
procedures that are highly qualitative in nature, thus limiting the
quantitative rigour of the practical interpretations made from these indices.
The statistical modelling approach to construct the latent health factor index
(LHFI) was recently developed to express ecological data, collected to
construct conventional multimetric health indices, in a rigorous quantitative
model that integrates qualitative features of ecosystem health and preconceived
ecological relationships among such features. This hierarchical modelling
approach allows (a) statistical inference of health for observed sites and (b)
prediction of health for unobserved sites, all accompanied by formal
uncertainty statements. Thus far, the LHFI approach has been demonstrated and
validated on freshwater ecosystems. The goal of this paper is to adapt this
approach to modelling estuarine ecosystem health, particularly that of the
previously unassessed system in Richibucto in New Brunswick, Canada. Field data
correspond to biotic health metrics that constitute the AZTI marine biotic
index (AMBI) and abiotic predictors preconceived to influence biota. We also
briefly discuss related LHFI research involving additional metrics that form
the infaunal trophic index (ITI). Our paper is the first to construct a
scientifically sensible model to rigorously identify the collective explanatory
capacity of salinity, distance downstream, channel depth, and silt-clay content
--- all regarded a priori as qualitatively important abiotic drivers ---
towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for
publication in PLoS One. See Journal reference and DOI belo
The calcium activated nucleotidases: A diverse family of soluble and membrane associated nucleotide hydrolyzing enzymes
It has long been known that the salivary glands of hematophagous (blood-feeding) arthropods secrete soluble apyrases, which are potent nucleotide hydrolyzing enzymes capable of hydrolyzing extracellular ATP and ADP, the latter being a major agonist contributing to platelet aggregation. Only recently, however, has the identification of proteins homologous to these apyrases been reported in non-blood-feeding organisms such as rodents and humans. In this review, we present an overview of the diverse family of apyrases first described in the blood-feeding arthropods, including the identification and characterization of the soluble and membrane-bound vertebrate enzymes homologous to these arthropod apyrases. We also describe the enzymatic properties and nucleotide specificities of the expressed enzymes, and insights gained into the structure and function of this calcium activated nucleotidase (CAN) family from biophysical, mutagenesis and crystallography studies. The potential therapeutic value of these proteins is also discussed
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Inclusive J/Ï production at mid-rapidity in pp collisions at âs = 5.02 TeV
Inclusive J/Ï production is studied in minimum-bias proton-proton collisions at a centre-of-mass energy of s = 5.02 TeV by ALICE at the CERN LHC. The measurement is performed at mid-rapidity (|y| < 0.9) in the dielectron decay channel down to zero transverse momentum pT, using a data sample corresponding to an integrated luminosity of Lint = 19.4 ± 0.4 nbâ1. The measured pT-integrated inclusive J/Ï production cross sec- tion is dÏ/dy = 5.64 ± 0.22(stat.) ± 0.33(syst.) ± 0.12(lumi.) ÎŒb. The pT-differential cross section d2Ï/dpTdy is measured in the pT range 0â10 GeV/c and compared with state-of- the-art QCD calculations. The J/Ï ăpTă and ăpT2ă are extracted and compared with results obtained at other collision energies. [Figure not available: see fulltext.]
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Measurement of Î (1520) production in pp collisions at âs=7TeV and pâPb collisions at âsNN=5.02TeV
The production of the Î (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in pâPb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Î (1520) â pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and pâPb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (Ï, K, KS0, p, Î) describes the shape of the Î (1520) transverse momentum distribution up to 3.5GeV/c in pâPb collisions. In the framework of this model, this observation suggests that the Î (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Î (1520) to the yield of the ground state particle Î remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in pâPb collisions on the Î (1520) yield
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Measurement of electrons from heavy-flavour hadron decays as a function of multiplicity in p-Pb collisions at âsNN = 5.02 TeV
The multiplicity dependence of electron production from heavy-flavour hadron decays as a function of transverse momentum was measured in p-Pb collisions at sNN = 5.02 TeV using the ALICE detector at the LHC. The measurement was performed in the centre-of-mass rapidity interval â1.07 < ycms< 0.14 and transverse momentum interval 2 < pT< 16 GeV/c. The multiplicity dependence of the production of electrons from heavy-flavour hadron decays was studied by comparing the pT spectra measured for different multiplicity classes with those measured in pp collisions (QpPb) and in peripheral p-Pb collisions (Qcp). The QpPb results obtained are consistent with unity within uncertainties in the measured pT interval and event classes. This indicates that heavy-flavour decay electron production is consistent with binary scaling and independent of the geometry of the collision system. Additionally, the results suggest that cold nuclear matter effects are negligible within uncertainties, in the production of heavy-flavour decay electrons at midrapidity in p-Pb collisions. [Figure not available: see fulltext.
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Measurement of prompt D0, D+, D*+, and DS+ production in pâPb collisions at âsNN = 5.02 TeV
The measurement of the production of prompt D0, D+, D*+, and DS+ mesons in protonâlead (pâPb) collisions at the centre-of-mass energy per nucleon pair of sNN = 5.02 TeV, with an integrated luminosity of 292 ± 11 ÎŒbâ1, are reported. Differential production cross sections are measured at mid-rapidity (â0.96 < ycms< 0.04) as a function of transverse momentum (pT) in the intervals 0 < pT< 36 GeV/c for D0, 1 < pT< 36 GeV/c for D+ and D*+, and 2 < pT< 24 GeV/c for D+ mesons. For each species, the nuclear modification factor RpPb is calculated as a function of pT using a proton-proton (pp) ref- erence measured at the same collision energy. The results are compatible with unity in the whole pT range. The average of the non-strange D mesons RpPb is compared with theoretical model predictions that include initial-state effects and parton transport model predictions. The pT dependence of the D0, D+, and D*+ nuclear modification factors is also reported in the interval 1 < pT< 36 GeV/c as a function of the collision centrality, and the central-to-peripheral ratios are computed from the D-meson yields measured in different centrality classes. The results are further compared with charged-particle measurements and a similar trend is observed in all the centrality classes. The ratios of the pT-differential cross sections of D0, D+, D*+, and DS+ mesons are also reported. The DS+ and D+ yields are compared as a function of the charged-particle multiplicity for several pT intervals. No modification in the relative abundances of the four species is observed with respect to pp collisions within the statistical and systematic uncertainties. [Figure not available: see fulltext.]
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