246 research outputs found
Sialylation on O-linked glycans protects von Willebrand factor from macrophage galactose lectin mediated clearance
Terminal sialylation determines the plasma half-life of von Willebrand factor (VWF). A role for macrophage galactose lectin (MGL) in regulating hyposialylated VWF clearance has recently been proposed. In this study, we showed that MGL influences physiological plasma VWF clearance. MGL inhibition was associated with a significantly extended mean residence time and 3-fold increase in endogenous plasma VWF antigen levels (P<0.05). Using a series of VWF truncations, we further demonstrated that the A1 domain of VWF is predominantly responsible for enabling the MGL interaction. Binding of both full-length and VWF-A1-A2-A3 to MGL was significantly enhanced in the presence of ristocetin (P<0.05), suggesting that the MGL-binding site in A1 is not fully accessible in globular VWF. Additional studies using different VWF glycoforms demonstrated that VWF O-linked glycans, clustered at either end of the A1 domain, play a key role in protecting VWF against MGLmediated clearance. Reduced sialylation has been associated with pathological, increased clearance of VWF in patients with von Willebrand disease. Herein, we demonstrate that specific loss of α2-3 linked sialylation from O-glycans results in markedly increased MGL-binding in vitro, and markedly enhanced MGL-mediated clearance of VWF in vivo. Our data further show that the asialoglycoprotein receptor (ASGPR) does not have a significant role in mediating the increased clearance of VWF following loss of O-sialylation. Conversely however, we observed that loss of N-linked sialylation from VWF drives enhanced circulatory clearance predominantly via the ASGPR. Collectively, our data support the hypothesis that in addition to regulating physiological VWF clearance, the MGL receptor works in tandem with ASGPR to modulate enhanced clearance of aberrantly sialylated VWF in the pathogenesis of von Willebrand disease
Observations of mixed-species bird flocks at Kichwa Tembo Camp, Kenya
Mixed-species foraging flocks were studied at Kichwa Tembo Camp on the edge of the Masai Mara National Reserve in Kenya between July and September 2004. Observations were made on 29 mixed-species flocks, in which 24 species participated. African Paradise-Flycatcher Terpsiphone viridis, Black-backed Puffback Dryoscopus cubla, Grey-backed Camaroptera Camaroptera brachyura, Collared Sunbird Hedydipna collars and Cabanis's Greenbul Phyllastrephus cabanisi were the most common participants in mixed-species flocks, as well as among the most frequently encountered bird species overall. The Black-backed Puffback was identified as the nuclear species in flocks due to their abundance and frequency with which they were followed by other species. Mixed-species flocks represent another niche dimension in this diverse bird community, but few of these species could be described as flock specialists; most of the birds observed in mixed-species flocks in this study were opportunistic attendant species, including the African Pygmy-Kingfisher Ispidina picta, not previously described as joining mixed-species flocks
Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)
Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression â„48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56 +CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) <50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL <50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naĂŻve and CD25+ CD4+ T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. Trial Registration: ClinicalTrials.gov NCT00084019
Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers
Search for the pentaquark in the reaction
A search for the \thp in the reaction was completed
using the CLAS detector at Jefferson Lab. A study of the same reaction,
published earlier, reported the observation of a narrow \thp resonance. The
present experiment, with more than 30 times the integrated luminosity of our
earlier measurement, does not show any evidence for a narrow pentaquark
resonance. The angle-integrated upper limit on \thp production in the mass
range of 1.52 to 1.56 GeV/c for the reaction is
0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and
angular distribution of \thp production. Using \lamstar production as an
empirical measure of rescattering in the deuteron, the cross section upper
limit for the elementary reaction is estimated to be
a factor of 10 higher, {\it i.e.}, nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment
Single pi+ Electroproduction on the Proton in the First and Second Resonance Regions at 0.25GeV^2 < Q^2 < 0.65GeV^2 Using CLAS
The ep -> e'pi^+n reaction was studied in the first and second nucleon
resonance regions in the 0.25 GeV^2 < Q^2 < 0.65 GeV^2 range using the CLAS
detector at Thomas Jefferson National Accelerator Facility. For the first time
the absolute cross sections were measured covering nearly the full angular
range in the hadronic center-of-mass frame. The structure functions sigma_TL,
sigma_TT and the linear combination sigma_T+epsilon*sigma_L were extracted by
fitting the phi-dependence of the measured cross sections, and were compared to
the MAID and Sato-Lee models.Comment: Accepted for publication in PR
Photodisintegration of He into p+t
The two-body photodisintegration of He into a proton and a triton has
been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson
Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system
in the energy range from 0.35 to 1.55 GeV were incident on a liquid He
target. This is the first measurement of the photodisintegration of He
above 0.4 GeV. The differential cross sections for the He
reaction have been measured as a function of photon-beam energy and
proton-scattering angle, and are compared with the latest model calculations by
J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the
calculations that include three-body mechanisms, thus confirming their
importance. These results reinforce the conclusion of our previous study of the
three-body breakup of He that demonstrated the great importance of
three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22
postscrip figure
photoproduction on the proton for photon energies from 0.675 to 2.875 GeV
Differential cross sections for the reaction have been
measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged
photon beam with energies from 0.675 to 2.875 GeV. The results reported here
possess greater accuracy in the absolute normalization than previous
measurements. They disagree with recent CB-ELSA measurements for the process at
forward scattering angles. Agreement with the SAID and MAID fits is found below
1 GeV. The present set of cross sections has been incorporated into the SAID
database, and exploratory fits have been extended to 3 GeV. Resonance couplings
have been extracted and compared to previous determinations.Comment: 18 pages, 48 figure
Exclusive electroproduction on the proton at CLAS
The reaction has been measured, using the 5.754
GeV electron beam of Jefferson Lab and the CLAS detector. This represents the
largest ever set of data for this reaction in the valence region. Integrated
and differential cross sections are presented. The , and
dependences of the cross section are compared to theoretical calculations based
on -channel meson-exchange Regge theory on the one hand and on quark handbag
diagrams related to Generalized Parton Distributions (GPDs) on the other hand.
The Regge approach can describe at the 30% level most of the features
of the present data while the two GPD calculations that are presented in this
article which succesfully reproduce the high energy data strongly underestimate
the present data. The question is then raised whether this discrepancy
originates from an incomplete or inexact way of modelling the GPDs or the
associated hard scattering amplitude or whether the GPD formalism is simply
inapplicable in this region due to higher-twists contributions, incalculable at
present.Comment: 29 pages, 29 figure
First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction
Spin transfer from circularly polarized real photons to recoiling hyperons
has been measured for the reactions and
. The data were obtained using the CLAS
detector at Jefferson Lab for center-of-mass energies between 1.6 and 2.53
GeV, and for . For the , the
polarization transfer coefficient along the photon momentum axis, , was
found to be near unity for a wide range of energy and kaon production angles.
The associated transverse polarization coefficient, , is smaller than
by a roughly constant difference of unity. Most significantly, the {\it
total} polarization vector, including the induced polarization ,
has magnitude consistent with unity at all measured energies and production
angles when the beam is fully polarized. For the this simple
phenomenology does not hold. All existing hadrodynamic models are in poor
agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review
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